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Although numerous studies on oxide catalysts for an efficient oxygen evolution reaction have been carried out to compare their catalytic performance and suggest new compositions, two significant constraints have been overlooked. One is the difference in electronic conduction behavior between catalysts (metallic versus insulating) and the other is the strong crystallographic surface orientation dependence of the catalysis in a crystal. Consequently, unless a comprehensive comparison of the oxygen-evolution catalytic activity between samples is made on a crystallographically identical surface with sufficient electron conduction, misleading interpretations on the catalytic performance and mechanism may be unavoidable. To overcome these limitations, we utilize both metallic (001) LaNiO 3 epitaxial thin films together with metal dopants and semiconducting (001) LaCoO 3 epitaxial thin films supported with a conductive interlayer. We identify that Fe, Cr, and Al are beneficial to enhance the catalysis in LaNiO 3 although their perovskite counterparts, LaFeO 3 , LaCrO 3 , and LaAlO 3 , with a large bandgap are inactive. Furthermore, semiconducting LaCoO 3 is found to have more than one order higher activity than metallic LaNiO 3 , in contrast to previous reports. Showing the importance of facilitating electron conduction, our work highlights the impact of the near-Fermi-level d-orbital states on the oxygen-evolution catalysis performance in perovskite oxides.

Elucidating intrinsic contribution of d-orbital states to oxygen evolution electrocatalysis in oxides.

Nature communications

biology

The advent of free-electron laser (FEL) sources delivering two synchronized pulses of different wavelengths (or colours) has made available a whole range of novel pump-probe experiments. This communication describes a major step forward using a new configuration of the FERMI FEL-seeded source to deliver two pulses with different wavelengths, each tunable independently over a broad spectral range with adjustable time delay. The FEL scheme makes use of two seed laser beams of different wavelengths and of a split radiator section to generate two extreme ultraviolet pulses from distinct portions of the same electron bunch. The tunability range of this new two-colour source meets the requirements of double-resonant FEL pump/FEL probe time-resolved studies. We demonstrate its performance in a proof-of-principle magnetic scattering experiment in Fe-Ni compounds, by tuning the FEL wavelengths to the Fe and Ni 3p resonances.

Widely tunable two-colour seeded free-electron laser source for resonant-pump resonant-probe magnetic scattering.

Nature communications

biology

Despite the success of checkpoint blockade in some cancer patients, there is an unmet need to improve outcomes. Targeting alternative pathways, such as costimulatory molecules (e.g. OX40, GITR, and 4-1BB), can enhance T cell immunity in tumor-bearing hosts. Here we describe the results from a phase Ib clinical trial (NCT02274155) in which 17 patients with locally advanced head and neck squamous cell carcinoma (HNSCC) received a murine anti-human OX40 agonist antibody (MEDI6469) prior to definitive surgical resection. The primary endpoint was to determine safety and feasibility of the anti-OX40 neoadjuvant treatment. The secondary objective was to assess the effect of anti-OX40 on lymphocyte subsets in the tumor and blood. Neoadjuvant anti-OX40 was well tolerated and did not delay surgery, thus meeting the primary endpoint. Peripheral blood phenotyping data show increases in CD4+ and CD8+ T cell proliferation two weeks after anti-OX40 administration. Comparison of tumor biopsies before and after treatment reveals an increase of activated, conventional CD4+ tumor-infiltrating lymphocytes (TIL) in most patients and higher clonality by TCRβ sequencing. Analyses of CD8+ TIL show increases in tumor-antigen reactive, proliferating CD103+ CD39+ cells in 25% of patients with evaluable tumor tissue (N = 4/16), all of whom remain disease-free. These data provide evidence that anti-OX40 prior to surgery is safe and can increase activation and proliferation of CD4+ and CD8+ T cells in blood and tumor. Our work suggests that increases in the tumor-reactive CD103+ CD39+ CD8+ TIL could serve as a potential biomarker of anti-OX40 clinical activity.

Neoadjuvant anti-OX40 (MEDI6469) therapy in patients with head and neck squamous cell carcinoma activates and expands antigen-specific tumor-infiltrating T cells.

Nature communications

biology

Friction and wear reduction by diamond-like carbon (DLC) in automotive applications can be affected by zinc-dialkyldithiophosphate (ZDDP), which is widely used in engine oils. Our experiments show that DLC's tribological behaviour in ZDDP-additivated oils can be optimised by tailoring its stiffness, surface nano-topography and hydrogen content. An optimal combination of ultralow friction and negligible wear is achieved using hydrogen-free tetrahedral amorphous carbon (ta-C) with moderate hardness. Softer coatings exhibit similarly low wear and thin ZDDP-derived patchy tribofilms but higher friction. Conversely, harder ta-Cs undergo severe wear and sub-surface sulphur contamination. Contact-mechanics and quantum-chemical simulations reveal that shear combined with the high local contact pressure caused by the contact stiffness and average surface slope of hard ta-Cs favour ZDDP fragmentation and sulphur release. In absence of hydrogen, this is followed by local surface cold welding and sub-surface mechanical mixing of sulphur resulting in a decrease of yield stress and wear.

Interplay of mechanics and chemistry governs wear of diamond-like carbon coatings interacting with ZDDP-additivated lubricants.

Nature communications

biology

For kesterite copper zinc tin sulfide/selenide (CZTSSe) solar cells to enter the market, in addition to efficiency improvements, the technological capability to produce flexible and large-area modules with homogeneous properties is necessary. Here, we report a greater than 10% efficiency for a cell area of approximately 0.5 cm 2 and a greater than 8% efficiency for a cell area larger than 2 cm 2 of certified flexible CZTSSe solar cells. By designing a thin and multi-layered precursor structure, the formation of defects and defect clusters, particularly tin-related donor defects, is controlled, and the open circuit voltage value is enhanced. Using statistical analysis, we verify that the cell-to-cell and within-cell uniformity characteristics are improved. This study reports the highest efficiency so far for flexible CZTSSe solar cells with small and large areas. These results also present methods for improving the efficiency and enlarging the cell area.

Flexible Cu2ZnSn(S,Se)4 solar cells with over 10% efficiency and methods of enlarging the cell area.

Nature communications

biology

Atoms interact with each other through the electromagnetic field, creating collective states that can radiate faster or slower than a single atom, i.e., super- and sub-radiance. When the field is confined to one dimension it enables infinite-range atom-atom interactions. Here we present the first report of infinite-range interactions between macroscopically separated atomic dipoles mediated by an optical waveguide. We use cold 87 Rb atoms in the vicinity of a single-mode optical nanofiber (ONF) that coherently exchange evanescently coupled photons through the ONF mode. In particular, we observe super-radiance of a few atoms separated by hundreds of resonant wavelengths. The same platform allows us to measure sub-radiance, a rarely observed effect, presenting a unique tool for quantum optics. This result constitutes a proof of principle for collective behavior of macroscopically delocalized atomic states, a crucial element for new proposals in quantum information and many-body physics.

Super-radiance reveals infinite-range dipole interactions through a nanofiber.

Nature communications

biology

Variations in N-acylethanolamines (NAE) levels are associated with obesity and metabolic comorbidities. Their role in the gut remains unclear. Therefore, we generated a mouse model of inducible intestinal epithelial cell (IEC)-specific deletion of N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD), a key enzyme involved in NAE biosynthesis (Napepld ∆IEC ). We discovered that Napepld ∆IEC mice are hyperphagic upon first high-fat diet (HFD) exposure, and develop exacerbated obesity and steatosis. These mice display hypothalamic Pomc neurons dysfunctions and alterations in intestinal and plasma NAE and 2-acylglycerols. After long-term HFD, Napepld ∆IEC mice present reduced energy expenditure. The increased steatosis is associated with higher gut and liver lipid absorption. Napepld ∆IEC mice display altered gut microbiota. Akkermansia muciniphila administration partly counteracts the IEC NAPE-PLD deletion effects. In conclusion, intestinal NAPE-PLD is a key sensor in nutritional adaptation to fat intake, gut-to-brain axis and energy homeostasis and thereby constitutes a novel target to tackle obesity and related disorders.

Intestinal epithelial N-acylphosphatidylethanolamine phospholipase D links dietary fat to metabolic adaptations in obesity and steatosis.

Nature communications

biology

The self-powered and ultra-broadband photodetectors based on photothermoelectric (PTE) effect are promising for diverse applications such as sensing, environmental monitoring, night vision and astronomy. The sensitivity of PTE photodetectors is determined by the Seebeck coefficient and the rising temperature under illumination. Previous PTE photodetectors mostly rely on traditional thermoelectric materials with Seebeck coefficients in the range of 100 μV K -1 , and array structures with multiple units are usually employed to enhance the photodetection performance. Herein, we demonstrate a reduced SrTiO 3 (r-STO) based PTE photodetector with sensitivity up to 1.2 V W -1 and broadband spectral response from 325 nm to 10.67 μm. The high performance of r-STO PTE photodetector is attributed to its intrinsic high Seebeck coefficient and phonon-enhanced photoresponse in the long wavelength infrared region. Our results open up a new avenue towards searching for novel PTE materials beyond traditional thermoelectric materials for low-cost and high-performance photodetector at room temperature.

Phonon-enhanced photothermoelectric effect in SrTiO3 ultra-broadband photodetector.

Nature communications

biology

Extended-coordination sphere interactions between dissolved metals and other ions, including electrolyte cations, are not known to perturb the electrochemical behavior of metal cations in water. Herein, we report the stabilization of higher-oxidation-state Np dioxocations in aqueous chloride solutions by hydrophobic tetra-n-alkylammonium (TAA + ) cations-an effect not exerted by fully hydrated Li + cations under similar conditions. Experimental and molecular dynamics simulation results indicate that TAA + cations not only drive enhanced coordination of anionic Cl - ligands to Np V/VI but also associate with the resulting Np complexes via non-covalent interactions, which together decrease the electrode potential of the Np VI /Np V couple by up to 220 mV (ΔΔG = -22.2 kJ mol -1 ). Understanding the solvation-dependent interplay between electrolyte cations and metal-oxo species opens an avenue for controlling the formation and redox properties of metal complexes in solution. It also provides valuable mechanistic insights into actinide separation processes that widely use quaternary ammonium cations as extractants or in room temperature ionic liquids.

Ion association with tetra-n-alkylammonium cations stabilizes higher-oxidation-state neptunium dioxocations.

Nature communications

biology

Increased extracellular Ca 2+ concentrations ([Ca 2+ ] ex ) trigger activation of the NLRP3 inflammasome in monocytes through calcium-sensing receptor (CaSR). To prevent extraosseous calcification in vivo, the serum protein fetuin-A stabilizes calcium and phosphate into 70-100 nm-sized colloidal calciprotein particles (CPPs). Here we show that monocytes engulf CPPs via macropinocytosis, and this process is strictly dependent on CaSR signaling triggered by increases in [Ca 2+ ] ex . Enhanced macropinocytosis of CPPs results in increased lysosomal activity, NLRP3 inflammasome activation, and IL-1β release. Monocytes in the context of rheumatoid arthritis (RA) exhibit increased CPP uptake and IL-1β release in response to CaSR signaling. CaSR expression in these monocytes and local [Ca 2+ ] in afflicted joints are increased, probably contributing to this enhanced response. We propose that CaSR-mediated NLRP3 inflammasome activation contributes to inflammatory arthritis and systemic inflammation not only in RA, but possibly also in other inflammatory conditions. Inhibition of CaSR-mediated CPP uptake might be a therapeutic approach to treating RA.

Calcium-sensing receptor-mediated NLRP3 inflammasome response to calciprotein particles drives inflammation in rheumatoid arthritis.

Nature communications

biology

Quantum magnets provide the simplest example of strongly interacting quantum matter, yet they continue to resist a comprehensive understanding above one spatial dimension. We explore a promising framework in two dimensions, the Dirac spin liquid (DSL) - quantum electrodynamics (QED 3 ) with 4 Dirac fermions coupled to photons. Importantly, its excitations include magnetic monopoles that drive confinement. We address previously open key questions - the symmetry actions on monopoles on square, honeycomb, triangular and kagome lattices. The stability of the DSL is enhanced on triangular and kagome lattices compared to bipartite (square and honeycomb) lattices. We obtain the universal signatures of the DSL on triangular and kagome lattices, including those of monopole excitations, as a guide to numerics and experiments on existing materials. Even when unstable, the DSL helps unify and organize the plethora of ordered phases in correlated two-dimensional materials.

Unifying description of competing orders in two-dimensional quantum magnets.

Nature communications

biology

The intermediate-band solar cell (IBSC) with quantum dots and a bulk semiconductor matrix has potential for high power conversion efficiency, exceeding the Shockley-Queisser limit. However, the IBSCs reported to date have been fabricated only by dry process and their efficiencies are limited, because their photo-absorption layers have low particle density of quantum dots, defects due to lattice strain, and low bandgap energy of bulk semiconductors. Here we present solution-processed IBSCs containing photo-absorption layers where lead sulfide quantum dots are densely dispersed in methylammonium lead bromide perovskite matrices with a high bandgap energy of 2.3 eV under undistorted conditions. We confirm that the present IBSCs exhibit two-step photon absorption via intermediate-band at room temperature by inter-subband photocurrent spectroscopy.

Solution-processed intermediate-band solar cells with lead sulfide quantum dots and lead halide perovskites.

Nature communications

biology

Hepatic de novo lipogenesis (DNL) converts carbohydrates into triglycerides and is known to influence systemic lipid homoeostasis. Here, we demonstrate that the zinc finger protein Zbtb20 is required for DNL. Mice lacking Zbtb20 in the liver exhibit hypolipidemia and reduced levels of liver triglycerides, along with impaired hepatic lipogenesis. The expression of genes involved in glycolysis and DNL, including that of two ChREBP isoforms, is decreased in livers of knockout mice. Zbtb20 binds to and enhances the activity of the ChREBP-α promoter, suggesting that altered metabolic gene expression is mainly driven by ChREBP. In addition, ChREBP-β overexpression largely restores hepatic expression of genes involved in glucose and lipid metabolism, and increases plasma and liver triglyceride levels in knockout mice. Finally, we show that Zbtb20 ablation protects from diet-induced liver steatosis and improves hepatic insulin resistance. We suggest ZBTB20 is an essential regulator of hepatic lipogenesis and may be a therapeutic target for the treatment of fatty liver disease.

Regulation of hepatic lipogenesis by the zinc finger protein Zbtb20.

Nature communications

biology

Beneficial modulation of the gut microbiome has high-impact implications not only in humans, but also in livestock that sustain our current societal needs. In this context, we have tailored an acetylated galactoglucomannan (AcGGM) fibre to match unique enzymatic capabilities of Roseburia and Faecalibacterium species, both renowned butyrate-producing gut commensals. Here, we test the accuracy of AcGGM within the complex endogenous gut microbiome of pigs, wherein we resolve 355 metagenome-assembled genomes together with quantitative metaproteomes. In AcGGM-fed pigs, both target populations differentially express AcGGM-specific polysaccharide utilization loci, including novel, mannan-specific esterases that are critical to its deconstruction. However, AcGGM-inclusion also manifests a "butterfly effect", whereby numerous metabolic changes and interdependent cross-feeding pathways occur in neighboring non-mannanolytic populations that produce short-chain fatty acids. Our findings show how intricate structural features and acetylation patterns of dietary fibre can be customized to specific bacterial populations, with potential to create greater modulatory effects at large.

Microbiota-directed fibre activates both targeted and secondary metabolic shifts in the distal gut.

Nature communications

biology

Alpha-galactosidase (α-Gal) is an enzyme responsible for the hydrolyzation of glycolipids and glycoprotein commonly found in dietary sources. More than 20% of the general population suffers from abdominal pain or discomfort caused by intestinal gas and by indigested or partially digested food residuals. Therefore, α-Gal is used in dietary supplements to reduce intestinal gases and help complex food digestion. Marketed enzyme-containing dietary supplements must be produced in accordance with the Food and Drug Administration (FDA) regulations for Current Good Manufacturing Practice (cGMPs). in this work we illustrated the process used to develop and validate a spectrophotometric enzymatic assay for α-Gal activity quantification in dietary supplements. The validation workflow included an initial statistical-phase optimization of materials, reagents, and conditions, and subsequently a comparative study with another fluorimetric assay. A final validation of method performance in terms of specificity, linearity, accuracy, intermediate-precision repeatability, and system precision was then executed. The proven method achieved good performance in the quantitative determination of α-Gal activity in commercial food supplements in accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals (ICH) guidelines and is suitable as a rapid in-house quality control test.

Intra-Laboratory Validation of Alpha-Galactosidase Activity Measurement in Dietary Supplements.

Molecules (Basel, Switzerland)

chemistry

Photocages have been successfully applied in cellular signaling studies for the controlled release of metabolites with high spatio-temporal resolution. Commonly, coumarin photocages are activated by UV light and the quantum yields of uncaging are relatively low, which can limit their applications in vivo. Here, syntheses, the determination of the photophysical properties, and quantum chemical calculations of 7-diethylamino-4-hydroxymethyl-thiocoumarin (thio-DEACM) and caged adenine nucleotides are reported and compared to the widely used 7-diethylamino-4-hydroxymethyl-coumarin (DEACM) caging group. In this comparison, thio-DEACM stands out as a phosphate cage with improved photophysical properties, such as red-shifted absorption and significantly faster photolysis kinetics.

Thiocoumarin Caged Nucleotides: Synthetic Access and Their Photophysical Properties.

Molecules (Basel, Switzerland)

chemistry

This paper experimentally investigates the influence of carbon nanotubes (CNTs) on phase composition, microstructure deterioration, thermal behavior, and residual mechanical strengths of cementitious composites exposed to elevated temperatures. Cement mortars with small dosages of CNTs, 0.05% and 0.2% by weight of cement, were prepared and then heated at 25 °C, 150 °C, 200 °C, 450 °C, and 600 °C for two hours before being tested. The results show positive impact of the CNTs on the hydration process of cement mortar at room temperature and at higher temperatures up to 200 °C. Decomposition of the hydration products is obvious at 450 °C, whereas sever deterioration in the microstructure occurs at 600 °C. The nano reinforcement and bridging effect of the CNTs are obvious up to 450 °C. Thermal behavior characterization shows that CNTs incorporation enhances the thermal conductivity of the unheated and heat-treated mortar specimens. The decomposition of the hydration products needs more heat in the presence of CNTs. Finally, presence of CNTs significantly enhances the residual compressive and flexural strengths of heated mortar specimens for all studied temperatures.

Influence of Carbon Nanotubes on Phase Composition, Thermal and Post-Heating Behavior of Cementitious Composites.

Molecules (Basel, Switzerland)

chemistry

Polyethylene glycol (PEG) particles were prepared using low-temperature supercritical assisted atomization (LTSAA) with carbon dioxide as the spraying medium or the co-solute and acetone as the solvent. The effects of several key factors on the particle size were investigated. These factors included the concentration of the PEG solution, precipitator temperature, saturator temperature, ratio of the volumetric flow rate of carbon dioxide to the PEG solution, and the molecular weight of PEG. Spherical and non-aggregated PEG particles, with a mean size of 1.7-3.2 µm, were obtained in this study. The optimal conditions to produce fine particles were found to be a low concentration of the PEG solution, a low precipitator temperature, and low molecular weight of the PEG. The phase behavior of the solution mixture in the saturator presented a qualitative relationship. At the optimized volumetric flow rate ratios, the composition of CO 2 in the feed streams was near the bubble points of the saturator temperatures. X-ray and differential scanning calorimetry analyses indicated that LTSAA-treated PEG had a reduced degree of crystallinity, which could be modulated via the precipitator temperature. PEG microparticles prepared by a LTSAA process would be promising carriers for drug-controlled formulations of PEG-drug composite particles.

Formation of Polyethylene Glycol Particles Using a Low-Temperature Supercritical Assisted Atomization Process.

Molecules (Basel, Switzerland)

chemistry

A catalytic enantioselective addition reaction of alkylzirconium species to aromatic aldehydes is reported. The reaction, facilitated by a chiral nonracemic diol ligand complex with Ti(O i Pr)₄, proceeds under mild and convenient conditions, and no premade organometallic reagents are required since the alkylzirconium nucleophiles are generated in situ by hydrozirconation of alkenes with the Schwartz reagent. The methodology is compatible with functionalized nucleophiles and a broad range of aromatic aldehydes.

Catalytic Enantioselective Addition of Organozirconium Reagents to Aldehydes.

Molecules (Basel, Switzerland)

chemistry

Two aggregation-induced emission (AIE) macrocycles ( DMP[5]-TPE and PCP[5]-TPE ) were prepared by embedding Tetraphenylethene (TPE) unit into the skeletons of Dimethoxypillar[5]arene (DMP[5]) and [15]Paracyclophane ([15]PCP) at meso position, respectively. In crystal, the PCP[5]-TPE showed a distorted cavity, and the incubation of hexane inside the DMP[5]-TPE cavity caused a distinct change in the molecular conformation compared to PCP[5]-TPE . There was no complexation between PCP[5]-TPE and 1,4-dicyanobutane (DCB). UV absorption experiments showed the distorted cavity of DMP[5]-TPE hindered association with DCB.

Tetraphenylethene-Embedded Pillar[5]arene and [15]Paracyclophane: Distorted Cavities and Host-Guest Binding Properties.

Molecules (Basel, Switzerland)

chemistry

Two new acylphloroglucinol derivatives, 13,14-didehydroxygarcicowin C ( 1 ) and 13,14-didehydroxyisoxanthochymol ( 2 ), have been isolated from the stems of Garcinia multiflora , together with seven known compounds ( 3 ⁻ 9 ). The structures of new compounds 1 and 2 were elucidated by MS and extensive 1D/2D NMR spectroscopic analyses. Among the isolates, 13,14-didehydroxy-isoxanthochymol ( 2 ) and sampsonione B ( 3 ) exhibited inhibition against lipopolysaccharide (LPS)-induced NF-κB activation in macrophages at 30 μM with relative luciferase activity values (inhibitory %) of 0.75 ± 0.03 (24 ± 4%) and 0.12 ± 0.03 (88 ± 4%), respectively. Additionally, sampsonione B ( 3 ) reduced LPS-induced nitric oxide (NO) production in murine RAW264.7 macrophages and did not induce cytotoxicity against RAW 264.7 cells after 24 h treatment. Compound 3 is worth further investigation and may be expectantly developed as an anti-inflammatory drug candidate.

Acylphloroglucinol Derivatives from Garcinia multiflora with Anti-Inflammatory Effect in LPS-Induced RAW264.7 Macrophages.

Molecules (Basel, Switzerland)

chemistry

The precise description of solute-water interactions is essential to understand the chemo-physical nature in hydration processes. Such a hydration thermodynamics for various solutes has been explored by means of explicit or implicit solvation methods. Using the Poisson-Boltzmann solvation model, the implicit models are well designed to reasonably predict the hydration free energies of polar solutes. The implicit model, however, is known to have shortcomings in estimating those for non-polar aromatic compounds. To investigate a cause of error, we employed a novel systematic framework of quantum-mechanical/molecular-mechanical (QM/MM) coupling protocol in explicit solvation manner, termed DFT-CES, based on the grid-based mean-field treatment. With the aid of DFT-CES, we delved into multiple energy parts, thereby comparing DFT-CES and PB models component-by-component. By applying the modified PB model to estimate the hydration free energies of non-polar solutes, we find a possibility to improve the predictability of PB models. We expect that this study could shed light on providing an accurate route to study the hydration thermodynamics for various solute compounds.

Hydration Thermodynamics of Non-Polar Aromatic Hydrocarbons: Comparison of Implicit and Explicit Solvation Models.

Molecules (Basel, Switzerland)

chemistry

A new direct method for β-selective glycosylation with an N -acetylglucosamine (GlcNAc) donor was developed. This substrate, which can be readily prepared from commercially available GlcNAc in two steps, contains a 4- O - tert -butyldimethylsilyl (TBDMS) protecting group as a key component. We found that this functionality could have a favorable effect on the reactivity of the GlcNAc donor. Glycosylation with the armed donor using primary alcohols in the presence of a catalytic amount of trimethylsilyl trifluoromethanesulfonate (TMSOTf) in 1,2-dichloroethane smoothly gave the desired coupling products in good yields with complete β-selectivity, while sterically hindered acceptors were less efficient.

A Direct Method for β-Selective Glycosylation with an N-Acetylglucosamine Donor Armed by a 4-O-TBDMS Protecting Group.

Molecules (Basel, Switzerland)

chemistry

This research assessed the molecular mechanism of procyanidins (PCs) against neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its metabolite 1-methyl-4-phenylpyridinium (MPP + ) induced Parkinson's disease (PD) models. In vitro, PC12 cells were incubated with PCs or deprenyl for 24 h, and then exposed to 1.5 mM MPP + for 24 h. In vivo, zebrafish larvae (AB strain) 3 days post-fertilization (dpf) were incubated with deprenyl or PCs in 400 μM MPTP for 4 days. Compared with MPP + /MPTP alone, PCs significantly improved antioxidant activities (e.g., glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT)), and decreased levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Furthermore, PCs significantly increased nuclear Nrf2 accumulation in PC12 cells and raised the expression of NQO1, HO-1, GCLM, and GCLC in both PC12 cells and zebrafish compared to MPP + /MPTP alone. The current study shows that PCs have neuroprotective effects, activate the nuclear factor-erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway and alleviate oxidative damage in MPP + /MPTP-induced PD models.

Protective Effects and Mechanisms of Procyanidins on Parkinson's Disease In Vivo and In Vitro.

Molecules (Basel, Switzerland)

chemistry

In this study, a novel dual-emission ratiometric fluorescent nanoprobe (RFN) was synthesized and ultilized for highly sensitive determination of mercury ions. In this nanoprobe, fluorescein isothiocyanate (FITC) doped silica (SiO 2 ) served as a reference signal, FITC-SiO 2 microspheres were synthesized and modified with amino groups, and then Au Nanoclusters (AuNCs) were combined with the amino groups on the surface of the FITC-SiO 2 microspheres to obtain the RFN. The selectivity, stability, and pH of the RFN were then optimized, and the determination of mercury ions was performed under optimal conditions. The probe fluorescence intensity ratio (F 520 nm/F 680 nm) and Hg 2+ concentration (1.0 × 10 -10 mol/L to 1.0 × 10 -8 mol/L) showed a good linear relationship, with a correlation coefficient of R 2 = 0.98802 and a detection limit of 1.0 × 10 -10 mol/L, respectively. The probe was used for the determination of trace mercury ion in water samples, and the recovery rate was 98.15~100.45%, suggesting a wide range of applications in monitoring pollutants, such as heavy metal ion and in the area of environmental protection.

Ratiometric Fluorescent Nanoprobe for Highly Sensitive Determination of Mercury Ions.

Molecules (Basel, Switzerland)

chemistry

Nowadays, much attention is paid to issues such as ecology and sustainability. Many consumers choose "green cosmetics", which are environmentally friendly creams, makeup, and beauty products, hoping that they are not harmful to health and reduce pollution. Moreover, the repeated mini-lock downs during the COVID-19 pandemic have fueled the awareness that body beauty is linked to well-being, both external and internal. As a result, consumer preferences for makeup have declined, while those for skincare products have increased. Nutricosmetics, which combines the benefits derived from food supplementation with the advantages of cosmetic treatments to improve the beauty of our body, respond to the new market demands. Food chemistry and cosmetic chemistry come together to promote both inside and outside well-being. A nutricosmetic optimizes the intake of nutritional microelements to meet the needs of the skin and skin appendages, improving their conditions and delaying aging, thus helping to protect the skin from the aging action of environmental factors. Numerous studies in the literature show a significant correlation between the adequate intake of these supplements, improved skin quality (both aesthetic and histological), and the acceleration of wound-healing. This review revised the main foods and bioactive molecules used in nutricosmetic formulations, their cosmetic effects, and the analytical techniques that allow the dosage of the active ingredients in the food.

The New Challenge of Green Cosmetics: Natural Food Ingredients for Cosmetic Formulations.

Molecules (Basel, Switzerland)

chemistry

Fungi can synthesize a wealth of secondary metabolites, which are widely used in the exploration of lead compounds of pharmaceutical or agricultural importance. Beauveria , Metarhizium , and Cordyceps are the most extensively studied fungi in which a large number of biologically active metabolites have been identified. However, relatively little attention has been paid to Purpureocillium lilacinum . P. lilacinum are soil-habituated fungi that are widely distributed in nature and are very important biocontrol fungi in agriculture, providing good biological control of plant parasitic nematodes and having a significant effect on Aphidoidea , T etranychus cinnbarinus , and Aleyrodidae . At the same time, it produces secondary metabolites with various biological activities such as anticancer, antimicrobial, and insecticidal. This review attempts to provide a comprehensive overview of the secondary metabolites of P. lilacinum , with emphasis on the chemical diversity and biological activity of these secondary metabolites and the biosynthetic pathways, and gives new insight into the secondary metabolites of medical and entomogenous fungi, which is expected to provide a reference for the development of medicine and agrochemicals in the future.

Secondary Metabolites of Purpureocilliumlilacinum.

Molecules (Basel, Switzerland)

chemistry

The currently available antidepressant agents necessitate the development of newer alternatives because of their serious adverse effects and costs. Traditional medicinal knowledge is likely the key that opens the door to discover new medicines. In Turkish folk medicine, the infusion prepared from aerial parts of Micromeria myrtifolia Boiss. & Hohen is used as pleasure and medicinal tea for its relaxing action. The present research was conceived to confirm the antidepressant's potential of this traditional medicinal plant. In this process, first of all, the collected and shade-dried aerial parts of M. myrtifolia were powdered and then, extracted using solvents with different polarity as follows; n -hexane, ethyl acetate (EtOAc), and methanol (MeOH). The antidepressant activity of the extracts was evaluated by using several in vivo and in vitro experimental models of depression. When the data obtained from the control and experimental groups were compared, it was determined that the MeOH extract was the most active. The active components of this extract were isolated and identified utilizing various chromatographic separation techniques. The MeOH extract was applied to reversed phase (RP-18) column chromatography to obtain five main fractions and they were tested on antidepressant activity models. The isolated compounds from the obtained fractions were elucidated as rosmarinic acid ( 1 ), myricetin ( 2 ), apigenin ( 3 ), and naringenin ( 4 ) which were assumed to be responsible for the antidepressant activity of the aerial parts. According to the results, rosmarinic acid, myricetin, apigenin, and naringenin showed statistically significant activity on forced swimming test and tetrabenazine-induced ptosis models, whereas only rosmarinic acid showed statistically significant activity on the tail suspension test. Apigenin displayed the highest inhibitory activity on MAO A and B enzymes. Studies in the future should be performed to investigate the antidepressant activity mechanism of these natural compounds. The current research could be an important step in the development of the new agents that can be used in the treatment of depression.

Assessment of Antidepressant Effect of the Aerial Parts of Micromeria myrtifolia Boiss. & Hohen on Mice.

Molecules (Basel, Switzerland)

chemistry

Here, we report the formation of homochiral supramolecular thin film from achiral molecules, by using circularly polarized light (CPL) only as a chiral source, on the condition that irradiation of CPL does not induce a photochemical change of the achiral molecules. Thin films of self-assembled structures consisting of chiral supramolecular fibrils was obtained from the triarylamine derivatives through evaporation of the self-assembled triarylamine solution. The homochiral supramolecular helices with the desired handedness was achieved by irradiation of circularly polarized visible light during the self-assembly process, and the chiral stability of supramolecular self-assembled product was achieved by photopolymerization of the diacetylene moieties at side chains of the building blocks, with irradiation of circularly polarized ultraviolet light. This work provides a novel methodology for the generation of homochiral supramolecular thin film from the corresponding achiral molecules.

Homochiral Supramolecular Thin Film from Self-Assembly of Achiral Triarylamine Molecules by Circularly Polarized Light.

Molecules (Basel, Switzerland)

chemistry

This study evaluated the in vitro antineoplastic and antiviral potential and in vivo toxicity of twelve extracts with different polarity obtained from the herbaceous perennial plant Geum urbanum L. ( Rosaceae ). In vitro cytotoxicity was determined by ISO 10993-5/2009 on bladder cancer, (T-24 and BC-3C), liver carcinoma (HEP-G2) and normal embryonic kidney (HEK-293) cell lines. The antineoplastic activity was elucidated through assays of cell clonogenicity, apoptosis induction, nuclear factor kappa B p65 (NFκB p65) activation and total glutathione levels. Neutral red uptake study was applied for antiviral activity. The most promising G. urbanum extract was analyzed by UHPLC-HRMS. The acute in vivo toxicity analysis was carried out following OEDC 423. The ethyl acetate extract of aerial parts (EtOAc-AP) exhibited the strongest antineoplastic activity on bladder cancer cell lines (IC 50 = 21.33-25.28 µg/mL) by inducing apoptosis and inhibiting NFκB p65 and cell clonogenicity. EtOAc and n -butanol extracts showed moderate antiviral activity against human adenovirus type 5 and human simplex virus type I. Seventy four secondary metabolites (gallic and ellagic acid derivatives, phenolic acids, flavonoids, etc.) were identified in EtOAc-AP by UHPLC-HRMS. This extract induced no signs of acute toxicity in liver and kidney specimens of H-albino mice in doses up to 210 mg/kg. In conclusion, our study contributes substantially to the detailed pharmacological characterization of G. urbanum , thus helping the development of health-promoting phytopreparations.

In Vitro Antineoplastic and Antiviral Activity and In Vivo Toxicity of Geum urbanum L. Extracts.

Molecules (Basel, Switzerland)

chemistry

A series of novel coumarin-based hydroxamate derivatives were designed and synthesized as histone deacetylase inhibitors (HDACis). Selective compounds showed a potent HDAC inhibition with nM IC 50 values, with the best compound ( 10e ) being nearly 90 times more active than vorinostat (SAHA) against HDAC1. Compounds 10e and 11d also increased the levels of acetylated histone H3 and H4, which is consistent with their strong HDAC inhibition. In addition, 10e and 11d displayed a higher potency toward human A549 and Hela cancer cell lines compared with SAHA. Moreover, 10e and 11d significantly arrested A549 cells at the G2/M phase and enhanced apoptosis. Molecular docking studies revealed the possible mode of interaction of compounds 10e and 12a with HDAC1. Our findings suggest that these novel coumarin-based HDAC inhibitors provide a promising scaffold for the development of new potential cancer chemotherapies.

Design, Synthesis and Biological Evaluation of Novel Coumarin-Based Hydroxamate Derivatives as Histone Deacetylase (Hdac) Inhibitors with Antitumor Activities.

Molecules (Basel, Switzerland)

chemistry

Drug transporters mediate the absorption, tissue distribution, and excretion of drugs. The cDNAs of P-glycoprotein, multidrug resistance proteins (MRPs/ABCC), breast cancer resistance protein (BCRP/ABCG2), peptide transporters (PEPTs/SLC15), proton-coupled folate transporters (PCFT/SLC46A1), organic anion transporting polypeptides (OATPs/SLCO), organic anion transporters (OATs/SLC22), organic cation transporters (OCTs/SLC22), and multidrug and toxin extrusions (MATEs/SLC47) have been isolated, and their functions have been elucidated. Enantioselectivity has been demonstrated in the pharmacokinetics and efficacy of drugs, and is important for elucidating the relationship with recognition of drugs by drug transporters from a chiral aspect. Enantioselectivity in the transport of drugs by drug transporters and the inhibitory effects of drugs on drug transporters has been summarized in this review.

Enantioselective Drug Recognition by Drug Transporters.

Molecules (Basel, Switzerland)

chemistry

Based on phenotypic screening, the major advantages of phosphorus dendrimers and dendrons as drugs allowed the discovery of new therapeutic applications, for instance, as anti-cancer and anti-tuberculosis agents. These biological activities depend on the nature of the chemical groups (neutral or cationic) on their surface as well as their generation. As lessons to learn, in the oncology domain, the increase in the generation of metallo-dendrimers is in the same direction as the anti-proliferative activities, in contrast to the development of polycationic dendrimers, where the most potent anti-tuberculosis phosphorus dendrimer was observed to have the lowest generation (G0). The examples presented in this original analysis of phosphorus dendrimers and dendrons provide support for the lessons learned and for the development of new nanoparticles in nanomedicine.

First-in-Class Phosphorus Dendritic Framework, a Wide Surface Functional Group Palette Bringing Noteworthy Anti-Cancer and Anti-Tuberculosis Activities: What Lessons to Learn?

Molecules (Basel, Switzerland)

chemistry

Cellulase enzymes deconstruct recalcitrant cellulose into soluble sugars, making them a biocatalyst of biotechnological interest for use in the nascent lignocellulosic bioeconomy. Cellobiohydrolases (CBHs) are cellulases capable of liberating many sugar molecules in a processive manner without dissociating from the substrate. Within the complete processive cycle of CBHs, dissociation from the cellulose substrate is rate limiting, but the molecular mechanism of this step is unknown. Here, we present a direct comparison of potential molecular mechanisms for dissociation via Hamiltonian replica exchange molecular dynamics of the model fungal CBH, Trichoderma reesei Cel7A. Computational rate estimates indicate that stepwise cellulose dethreading from the binding tunnel is 4 orders of magnitude faster than a clamshell mechanism, in which the substrate-enclosing loops open and release the substrate without reversing. We also present the crystal structure of a disulfide variant that covalently links substrate-enclosing loops on either side of the substrate-binding tunnel, which constitutes a CBH that can only dissociate via stepwise dethreading. Biochemical measurements indicate that this variant has a dissociation rate constant essentially equivalent to the wild type, implying that dethreading is likely the predominant mechanism for dissociation.

The dissociation mechanism of processive cellulases.

Proceedings of the National Academy of Sciences of the United States of America

multi

In the noisy cellular environment, gene products are subject to inherent random fluctuations in copy numbers over time. How cells ensure precision in the timing of key intracellular events despite such stochasticity is an intriguing fundamental problem. We formulate event timing as a first-passage time problem, where an event is triggered when the level of a protein crosses a critical threshold for the first time. Analytical calculations are performed for the first-passage time distribution in stochastic models of gene expression. Derivation of these formulas motivates an interesting question: Is there an optimal feedback strategy to regulate the synthesis of a protein to ensure that an event will occur at a precise time, while minimizing deviations or noise about the mean? Counterintuitively, results show that for a stable long-lived protein, the optimal strategy is to express the protein at a constant rate without any feedback regulation, and any form of feedback (positive, negative, or any combination of them) will always amplify noise in event timing. In contrast, a positive feedback mechanism provides the highest precision in timing for an unstable protein. These theoretical results explain recent experimental observations of single-cell lysis times in bacteriophage [Formula: see text] Here, lysis of an infected bacterial cell is orchestrated by the expression and accumulation of a stable [Formula: see text] protein up to a threshold, and precision in timing is achieved via feedforward rather than feedback control. Our results have broad implications for diverse cellular processes that rely on precise temporal triggering of events.

First-passage time approach to controlling noise in the timing of intracellular events.

Proceedings of the National Academy of Sciences of the United States of America

multi

The global health community has earmarked a number of diseases for elimination or eradication, and these goals have often been praised on the premise of long-run cost savings. However, decision makers must contend with a multitude of demands on health budgets in the short or medium term, and costs per case often rise as the burden of a disease falls, rendering such efforts beyond the cost-effective use of scarce resources. In addition, these decisions must be made in the presence of substantial uncertainty regarding the feasibility and costs of elimination or eradication efforts. Therefore, analytical frameworks are necessary to consider the additional effort for reaching global goals, like elimination or eradication, that are beyond the cost-effective use of country resources. We propose a modification to the net-benefit framework to consider the implications of switching from an optimal strategy, in terms of cost-per-burden averted, to a strategy with a higher likelihood of meeting the global target of elimination or eradication. We illustrate the properties of our framework by considering the economic case of efforts to eliminate the transmission of gambiense human African trypanosomiasis (gHAT), a vector-borne, parasitic disease in West and Central Africa, by 2030.

Economic evaluation of disease elimination: An extension to the net-benefit framework and application to human African trypanosomiasis.

Proceedings of the National Academy of Sciences of the United States of America

multi

Exposure to parental separation or divorce during childhood has been associated with an increased risk for physical morbidity during adulthood. Here we tested the hypothesis that this association is primarily attributable to separated parents who do not communicate with each other. We also examined whether early exposure to separated parents in conflict is associated with greater viral-induced inflammatory response in adulthood and in turn with increased susceptibility to viral-induced upper respiratory disease. After assessment of their parents' relationship during their childhood, 201 healthy volunteers, age 18-55 y, were quarantined, experimentally exposed to a virus that causes a common cold, and monitored for 5 d for the development of a respiratory illness. Monitoring included daily assessments of viral-specific infection, objective markers of illness, and local production of proinflammatory cytokines. Adults whose parents lived apart and never spoke during their childhood were more than three times as likely to develop a cold when exposed to the upper respiratory virus than adults from intact families. Conversely, individuals whose parents were separated but communicated with each other showed no increase in risk compared with those from intact families. These differences persisted in analyses adjusted for potentially confounding variables (demographics, current socioeconomic status, body mass index, season, baseline immunity to the challenge virus, affectivity, and childhood socioeconomic status). Mediation analyses were consistent with the hypothesis that greater susceptibility to respiratory infectious illness among the offspring of noncommunicating parents was attributable to a greater local proinflammatory response to infection.

Offspring of parents who were separated and not speaking to one another have reduced resistance to the common cold as adults.

Proceedings of the National Academy of Sciences of the United States of America

multi

Ethics in social science experimentation and data collection are often discussed but rarely articulated in writing as part of research outputs. Although papers typically reference human subjects research approvals from relevant institutional review boards, most recognize that such boards do not carry out comprehensive ethical assessments. We propose a structured ethics appendix to provide details on the following: policy equipoise, role of the researcher, potential harms to participants and nonparticipants, conflicts of interest, intellectual freedom, feedback to participants, and foreseeable misuse of research results. We discuss each of these and some of the norms and challenging situations of each. We believe that discussing such issues explicitly in appendices of papers, even if briefly, will serve two purposes: more complete communication of ethics can improve discussions of papers and can clarify and improve the norms themselves.

A call for structured ethics appendices in social science papers.

Proceedings of the National Academy of Sciences of the United States of America

multi

Oil and gas wells with compromised integrity are a concern because they can potentially leak hydrocarbons or other fluids into groundwater and/or the atmosphere. Most states in the United States require some form of integrity testing, but few jurisdictions mandate widespread testing and open reporting on a scale informative for leakage risk assessment. In this study, we searched 33 US state oil and gas regulatory agency databases and identified records useful for evaluating well integrity in Colorado, New Mexico, and Pennsylvania. In total, we compiled 474,621 testing records from 105,031 wells across these states into a uniform dataset. We found that 14.1% of wells tested prior to 2018 in Pennsylvania exhibited sustained casing pressure (SCP) or casing vent flow (CVF)-two indicators of compromised well integrity. Data from different hydrocarbon-producing regions within Colorado and New Mexico revealed a wider range (0.3 to 26.5%) of SCP and/or CVF occurrence than previously reported, highlighting the need to better understand regional trends in well integrity. Directional wells were more likely to exhibit SCP and/or CVF than vertical wells in Colorado and Pennsylvania, and their installation corresponded with statewide increases in SCP and/or CVF occurrence in Colorado (2005 to 2009) and Pennsylvania (2007 to 2011). Testing the ground around wells for indicators of gas leakage is not a widespread practice in the states considered. However, 3.0% of Colorado wells tested and 0.1% of New Mexico wells tested exhibited a degree of SCP sufficient to potentially induce leakage outside the well.

Public data from three US states provide new insights into well integrity.

Proceedings of the National Academy of Sciences of the United States of America

multi

Human evolution is widely thought to have involved a particular expansion of prefrontal cortex. This popular notion has recently been challenged, although controversies remain. Here we show that the prefrontal region of both human and nonhuman primates holds about 8% of cortical neurons, with no clear difference across humans and other primates in the distribution of cortical neurons or white matter cells along the anteroposterior axis. Further, we find that the volumes of human prefrontal gray and white matter match the expected volumes for the number of neurons in the gray matter and for the number of other cells in the white matter compared with other primate species. These results indicate that prefrontal cortical expansion in human evolution happened along the same allometric trajectory as for other primate species, without modification of the distribution of neurons across its surface or of the volume of the underlying white matter. We thus propose that the most distinctive feature of the human prefrontal cortex is its absolute number of neurons, not its relative volume.

No relative expansion of the number of prefrontal neurons in primate and human evolution.

Proceedings of the National Academy of Sciences of the United States of America

multi

Resolution of inflammation has emerged as an active process in immunobiology, with cells of the mononuclear phagocyte system being critical in mediating efferocytosis and wound debridement and bridging the gap between innate and adaptive immunity. Here we investigated the roles of cytochrome P450 (CYP)-derived epoxy-oxylipins in a well-characterized model of sterile resolving peritonitis in the mouse. Epoxy-oxylipins were produced in a biphasic manner during the peaks of acute (4 h) and resolution phases (24-48 h) of the response. The epoxygenase inhibitor SKF525A (epoxI) given at 24 h selectively inhibited arachidonic acid- and linoleic acid-derived CYP450-epoxy-oxlipins and resulted in a dramatic influx in monocytes. The epoxI-recruited monocytes were strongly GR1(+), Ly6c(hi), CCR2(hi), CCL2(hi), and CX3CR1(lo) In addition, expression of F4/80 and the recruitment of T cells, B cells, and dendritic cells were suppressed. sEH (Ephx2)(-/-) mice, which have elevated epoxy-oxylipins, demonstrated opposing effects to epoxI-treated mice: reduced Ly6c(hi) monocytes and elevated F4/80(hi) macrophages and B, T, and dendritic cells. Ly6c(hi) and Ly6c(lo) monocytes, resident macrophages, and recruited dendritic cells all showed a dramatic change in their resolution signature following in vivo epoxI treatment. Markers of macrophage differentiation CD11b, MerTK, and CD103 were reduced, and monocyte-derived macrophages and resident macrophages ex vivo showed greatly impaired phagocytosis of zymosan and efferocytosis of apoptotic thymocytes following epoxI treatment. These findings demonstrate that epoxy-oxylipins have a critical role in monocyte lineage recruitment and activity to promote inflammatory resolution and represent a previously unidentified internal regulatory system governing the establishment of adaptive immunity.

CYP450-derived oxylipins mediate inflammatory resolution.

Proceedings of the National Academy of Sciences of the United States of America

multi

The intracellular environment is crowded and heterogeneous. Although the thermodynamic stability of nucleic acid duplexes is predictable in dilute solutions, methods of predicting such stability under specific intracellular conditions are not yet available. We recently showed that the nearest-neighbor model for self-complementary DNA is valid under molecular crowding condition of 40% polyethylene glycol with an average molecular weight of 200 (PEG 200) in 100 mM NaCl. Here, we determined nearest-neighbor parameters for DNA duplex formation under the same crowding condition to predict the thermodynamics of DNA duplexes in the intracellular environment. Preferential hydration of the nucleotides was found to be the key factor for nearest-neighbor parameters in the crowding condition. The determined parameters were shown to predict the thermodynamic parameters (∆ H °, ∆ S °, and ∆ G ° 37 ) and melting temperatures ( T m ) of the DNA duplexes in the crowding condition with significant accuracy. Moreover, we proposed a general method for predicting the stability of short DNA duplexes in different cosolutes based on the relationship between duplex stability and the water activity of the cosolute solution. The method described herein would be valuable for investigating biological processes that occur under specific intracellular crowded conditions and for the application of DNA-based biotechnologies in crowded environments.

Nearest-neighbor parameters for predicting DNA duplex stability in diverse molecular crowding conditions.

Proceedings of the National Academy of Sciences of the United States of America

multi

Lithium-sulfur batteries (Li-S batteries) have attracted intense interest because of their high specific capacity and low cost, although they are still hindered by severe capacity loss upon cycling caused by the soluble lithium polysulfide intermediates. Although many structure innovations at the material and device levels have been explored for the ultimate goal of realizing long cycle life of Li-S batteries, it remains a major challenge to achieve stable cycling while avoiding energy and power density compromises caused by the introduction of significant dead weight/volume and increased electrochemical resistance. Here we introduce an ultrathin composite film consisting of naphthalimide-functionalized poly(amidoamine) dendrimers and graphene oxide nanosheets as a cycling stabilizer. Combining the dendrimer structure that can confine polysulfide intermediates chemically and physically together with the graphene oxide that renders the film robust and thin (<1% of the thickness of the active sulfur layer), the composite film is designed to enable stable cycling of sulfur cathodes without compromising the energy and power densities. Our sulfur electrodes coated with the composite film exhibit very good cycling stability, together with high sulfur content, large areal capacity, and improved power rate.

Ultrathin dendrimer-graphene oxide composite film for stable cycling lithium-sulfur batteries.

Proceedings of the National Academy of Sciences of the United States of America

multi

The olfactory system receives extensive serotonergic inputs from the dorsal raphe, a nucleus involved in control of behavior, regulation of mood, and modulation of sensory processing. Although many studies have investigated how serotonin modulates the olfactory bulb, few have focused on the anterior piriform cortex (aPC), a region important for olfactory learning and encoding of odor identity and intensity. Specifically, the mechanism and functional significance of serotonergic modulation of the aPC remain largely unknown. Here we used pharmacologic, optogenetic, and fiber photometry techniques to examine the serotonergic modulation of neural activity in the aPC in vitro and in vivo. We found that serotonin (5-HT) reduces the excitability of pyramidal neurons directly via 5-HT 2C receptors, phospholipase C, and calcium-activated potassium (BK) channels. Furthermore, endogenous serotonin attenuates odor-evoked calcium responses in aPC pyramidal neurons. These findings identify the mechanism underlying serotonergic modulation of the aPC and shed light on its potential role.

Serotonergic afferents from the dorsal raphe decrease the excitability of pyramidal neurons in the anterior piriform cortex.

Proceedings of the National Academy of Sciences of the United States of America

multi

Activating mutations in the KIT or PDGFRA receptor tyrosine kinases are hallmarks of gastrointestinal stromal tumor (GIST). The biological underpinnings of recurrence following resection or disease progression beyond kinase mutation are poorly understood. Utilizing chromatin immunoprecipitation with sequencing of tumor samples and cell lines, we describe the enhancer landscape of GIST, highlighting genes that reinforce and extend our understanding of these neoplasms. A group of core transcription factors can be distinguished from others unique to localized and metastatic disease. The transcription factor HAND1 emerges in metastatic disease, binds to established GIST-associated enhancers, and facilitates GIST cell proliferation and KIT gene expression. The pattern of transcription factor expression in primary tumors is predictive of metastasis-free survival in GIST patients. These results provide insight into the enhancer landscape and transcription factor network underlying GIST, and define a unique strategy for predicting clinical behavior of this disease.

Gastrointestinal stromal tumor enhancers support a transcription factor network predictive of clinical outcome.

Proceedings of the National Academy of Sciences of the United States of America

multi

The endangered whale shark ( Rhincodon typus ) is the largest fish on Earth and a long-lived member of the ancient Elasmobranchii clade. To characterize the relationship between genome features and biological traits, we sequenced and assembled the genome of the whale shark and compared its genomic and physiological features to those of 83 animals and yeast. We examined the scaling relationships between body size, temperature, metabolic rates, and genomic features and found both general correlations across the animal kingdom and features specific to the whale shark genome. Among animals, increased lifespan is positively correlated to body size and metabolic rate. Several genomic traits also significantly correlated with body size, including intron and gene length. Our large-scale comparative genomic analysis uncovered general features of metazoan genome architecture: Guanine and cytosine (GC) content and codon adaptation index are negatively correlated, and neural connectivity genes are longer than average genes in most genomes. Focusing on the whale shark genome, we identified multiple features that significantly correlate with lifespan. Among these were very long gene length, due to introns being highly enriched in repetitive elements such as CR1-like long interspersed nuclear elements, and considerably longer neural genes of several types, including connectivity, activity, and neurodegeneration genes. The whale shark genome also has the second slowest evolutionary rate observed in vertebrates to date. Our comparative genomics approach uncovered multiple genetic features associated with body size, metabolic rate, and lifespan and showed that the whale shark is a promising model for studies of neural architecture and lifespan.

The whale shark genome reveals how genomic and physiological properties scale with body size.

Proceedings of the National Academy of Sciences of the United States of America

multi

Synaptotagmins (Syts) act as Ca 2+ sensors in neurotransmitter release by virtue of Ca 2+ -binding to their two C 2 domains, but their mechanisms of action remain unclear. Puzzlingly, Ca 2+ -binding to the C 2 B domain appears to dominate Syt1 function in synchronous release, whereas Ca 2+ -binding to the C 2 A domain mediates Syt7 function in asynchronous release. Here we show that crystal structures of the Syt7 C 2 A domain and C 2 AB region, and analyses of intrinsic Ca 2+ -binding to the Syt7 C2 domains using isothermal titration calorimetry, did not reveal major differences that could explain functional differentiation between Syt7 and Syt1. However, using liposome titrations under Ca 2+ saturating conditions, we show that the Syt7 C 2 A domain has a very high membrane affinity and dominates phospholipid binding to Syt7 in the presence or absence of l-α-phosphatidylinositol 4,5-diphosphate (PIP 2 ). For Syt1, the two Ca 2+ -saturated C 2 domains have similar affinities for membranes lacking PIP 2 , but the C 2 B domain dominates binding to PIP 2 -containing membranes. Mutagenesis revealed that the dramatic differences in membrane affinity between the Syt1 and Syt7 C 2 A domains arise in part from apparently conservative residue substitutions, showing how striking biochemical and functional differences can result from the cumulative effects of subtle residue substitutions. Viewed together, our results suggest that membrane affinity may be a key determinant of the functions of Syt C 2 domains in neurotransmitter release.

Exceptionally tight membrane-binding may explain the key role of the synaptotagmin-7 C2A domain in asynchronous neurotransmitter release.

Proceedings of the National Academy of Sciences of the United States of America

multi

Two different types of mechanisms are at present suggested for the O-O bond-formation step in photosystem II. The first one is a coupling between an oxyl radical and a bridging oxo. The second one is a nucleophilic water attack on a terminal oxo (or oxyl) group. In the present short paper, the six most reasonable versions of the latter mechanism have been studied and compared with the oxo-oxyl mechanism. The barriers are found to be much too high for the water attack, and that mechanism can therefore safely be ruled out. The reason is that the protonated peroxide product is always very high in energy.

Nucleophilic water attack is not a possible mechanism for O-O bond formation in photosystem II.

Proceedings of the National Academy of Sciences of the United States of America

multi

Actively transcribed genes in mammals are decorated by H3K79 methylation, which is correlated with transcription levels and is catalyzed by the histone methyltransferase DOT1L. DOT1L is required for mammalian development, and the inhibition of its catalytic activity has been extensively studied for cancer therapy; however, the mechanisms underlying DOT1L's functions in normal development and cancer pathogenesis remain elusive. To dissect the relationship between H3K79 methylation, cellular differentiation, and transcription regulation, we systematically examined the role of DOT1L and its catalytic activity in embryonic stem cells (ESCs). DOT1L is dispensable for ESC self-renewal but is required for establishing the proper expression signature of neural progenitor cells, while catalytic inactivation of DOT1L has a lesser effect. Furthermore, DOT1L loss, rather than its catalytic inactivation, causes defects in glial cell specification. Although DOT1L loss by itself has no major defect in transcription elongation, transcription elongation defects seen with the super elongation complex inhibitor KL-2 are exacerbated in DOT1L knockout cells, but not in catalytically dead DOT1L cells, revealing a role of DOT1L in promoting productive transcription elongation that is independent of H3K79 methylation. Taken together, our study reveals a catalytic-independent role of DOT1L in modulating cell-fate determination and in transcriptional elongation control.

DOT1L-controlled cell-fate determination and transcription elongation are independent of H3K79 methylation.

Proceedings of the National Academy of Sciences of the United States of America

multi

China has implemented an emission trading system (ETS) to reduce its ever-increasing greenhouse gas emissions while maintaining rapid economic growth. With low carbon prices and infrequent allowance trading, whether China's ETS is an effective approach for climate mitigation has entered the center of the policy and research debate. Utilizing China's regional ETS pilots as a quasi-natural experiment, we provide a comprehensive assessment of the effects of ETS on firm carbon emissions and economic outcomes by means of a matched difference-in-differences (DID) approach. The empirical analysis is based on a unique panel dataset of firm tax records in the manufacturing and public utility sectors during 2009 to 2015. We show unambiguous evidence that the regional ETS pilots are effective in reducing firm emissions, leading to a 16.7% reduction in total emissions and a 9.7% reduction in emission intensity. Regulated firms achieve emission abatement through conserving energy consumption and switching to low-carbon fuels. The economic consequences of the ETS are mixed. On one hand, the ETS has a negative impact on employment and capital input; on the other hand, the ETS incentivizes regulated firms to improve productivity. In the aggregate, the ETS does not exhibit statistically significant effects on output and export. We also find that the ETS displays notable heterogeneity across pilots. Mass-based allowance allocation rules, higher carbon prices, and active allowance trading contribute to more pronounced effects in emission abatement.

The effectiveness of China's regional carbon market pilots in reducing firm emissions.

Proceedings of the National Academy of Sciences of the United States of America

multi

We recently reported that social choice-induced voluntary abstinence prevents incubation of methamphetamine craving in rats. This inhibitory effect was associated with activation of protein kinase-Cδ (PKCδ)-expressing neurons in central amygdala lateral division (CeL). In contrast, incubation of craving after forced abstinence was associated with activation of CeL-expressing somatostatin (SOM) neurons. Here we determined the causal role of CeL PKCδ and SOM in incubation using short-hairpin RNAs against PKCδ or SOM that we developed and validated. We injected two groups with shPKCδ or shCtrl PKCδ into CeL and trained them to lever press for social interaction (6 d) and then for methamphetamine infusions (12 d). We injected two other groups with shSOM or shCtrl SOM into CeL and trained them to lever press for methamphetamine infusions (12 d). We then assessed relapse to methamphetamine seeking after 1 and 15 abstinence days. Between tests, the rats underwent either social choice-induced abstinence (shPKCδ groups) or homecage forced abstinence (shSOM groups). After test day 15, we assessed PKCδ and SOM, Fos, and double-labeled expression in CeL and central amygdala medial division (CeM). shPKCδ CeL injections decreased Fos in CeL PKCδ-expressing neurons, increased Fos in CeM output neurons, and reversed the inhibitory effect of social choice-induced abstinence on incubated drug seeking on day 15. In contrast, shSOM CeL injections decreased Fos in CeL SOM-expressing neurons, decreased Fos in CeM output neurons, and decreased incubated drug seeking after 15 forced abstinence days. Our results identify dissociable central amygdala mechanisms of abstinence-dependent expression or inhibition of incubation of craving.

Abstinence-dependent dissociable central amygdala microcircuits control drug craving.

Proceedings of the National Academy of Sciences of the United States of America

multi

Dynamic molecular crystals have recently received ample attention as an emerging class of energy-transducing materials, yet have fallen short of developing into fully realized actuators. Through the trans - cis surface isomerization of three crystalline azobenzene materials, here, we set out to extensively characterize the light-to-work energy conversion of photoinduced bending in molecular crystals. We distinguish the azobenzene single crystals from commonly used actuators through quantitative performance evaluation and specific performance indices. Bending molecular crystals have an operating range comparable to that of microactuators such as microelectromechanical systems and a work-generating capacity and dynamic performance that qualifies them to substitute micromotor drivers in mechanical positioning and microgripping tasks. Finite element modeling, applied to determine the surface photoisomerization parameters, allowed for predicting and optimizing the mechanical response of these materials. Utilizing mechanical characterization and numerical simulation tools proves essential in accelerating the introduction of dynamic molecular crystals into soft microrobotics applications.

Performance of molecular crystals in conversion of light to mechanical work.

Proceedings of the National Academy of Sciences of the United States of America

multi

Contamination of soils with per- and polyfluoroalkyl substances (PFASs) is a global problem, in particular at fire-fighter training sites due to the usage of PFAS-containing aqueous fire-fighting foams (AFFFs). In this study, an electrodialytic remediation method was applied for the first time to remove PFASs from contaminated soil. The electrodialytic remediation system was evaluated in a laboratory-scale experiment with current densities of 0.19 mA cm -2 and 0.38 mA cm -2 over 21 days, using PFAS-contaminated soil from a fire-fighter training site at Stockholm Arlanda Airport, Sweden. Of the 23 PFASs targeted, significant (p < 0.05) PFAS electromigration towards the anode was observed for C 3 -C 7 perfluoroalkyl carboxylates (PFCAs) (PFBA, PFPeA, PFHxA, PFOA) and C 4 , C 6 , and C 8 perfluoroalkane sulfonates (PFSAs) (PFBS, PFHxS, PFOS) since these PFASs were predominantly negatively charged. In contrast to the electromigration of the charged PFASs, N-methyl perfluorooctane sulfonamide (MeFOSA), perfluorooctane sulfonamidoacetic acid (FOSAA) and ethyl FOSAA (EtFOSAA) showed significant (p < 0.05) transport towards the cathode, which is probably attributed to electro-osmotic flow of these predominantly neutral PFASs. Mass balance calculations showed that for the shortest-chained PFASs (i.e., PFBA, PFPeA, PFHxA, PFBS, and PFHxS), up to 20% was extracted from the soil to the anolyte, which showed that electrodialysis is a possible in-situ remediation technique for PFAS-contaminated soil.

Electrodialytic per- and polyfluoroalkyl substances (PFASs) removal mechanism for contaminated soil.

Chemosphere

chemistry

Scientists are on the lookout for a practical model that can serve as a standard for sorting out, identifying, and characterizing microplastics which are common occurrences in water sources and wastewaters. The microbeads (MBs) used in cosmetics and discharged into the sewer systems after use cause substantial microplastics pollution in the receiving waters. Today, the use of plastic microbeads in cosmetics is banned. The existing use cases are to be discontinued within a few years. Yet, there are no restrictions regarding the use of microbeads in a number of industries, cleaning products, pharmaceuticals and medical practices. In this context, the determination and classification of MBs which had so far been discharged to water sources and which continue to be discharged, represent crucial problems. In this work, we examined a new approach for the classification of MBs based on microscopic images. For classification purposes, Convolutional Neural Network (CNN) -a Deep Learning algorithm- was employed, whereas GoogLeNet architecture served as the model. The network is built from scratch, and trained then after tested on a total of 42928 images containing MBs in 5 distinct cleansers. The study performed with the CNN which achieved a classification performance of 89% for MBs in wastewater.

Use of a convolutional neural network for the classification of microbeads in urban wastewater.

Chemosphere

chemistry

Perfluorinated alkyl acids (PFAAs) are environmental contaminants that have been used in many products for over 50 years. Interest and concern has grown since 2000 on the widespread presence of PFAAs, when it was discovered that PFAAs were present in wildlife samples around the northern hemisphere. Since then, several studies have reported PFAAs in wildlife from many locations, including the remote regions of Antarctica and the Arctic. Although there are a multitude of studies, few have reported PFAA concentrations in reptiles and wildlife in the Southern Hemisphere. This study investigated the presence of PFAAs in the plasma of Nile crocodiles (Crocodylus niloticus) from South Africa. Crocodiles were captured from five sites in and around the Kruger National Park, South Africa, and plasma samples examined for PFAAs. Perfluorooctane sulfonate (PFOS) was the most frequent PFAA detected; with median values of 13.5 ng/g wet mass in crocodiles. In addition to PFOS, long chain perfluorinated carboxylic acids were also detected. Correlations between total length and PFAA load were investigated, as were differences in PFAA accumulation between sexes. No correlations were seen between crocodile size, nor were there sex-related differences. Spatial differences were examined and significant differences were observed in samples collected from the different sites (p < 0.05). Flag Boshielo Dam had the highest PFOS measurements, with a median concentration of 50.3 ng/g wet mass, when compared to the other sites (median concentrations at other sites below 14.0 ng/g wet mass). This suggests a point source of PFOS in this area.

Perfluorinated alkyl acids in the plasma of South African crocodiles (Crocodylus niloticus).

Chemosphere

chemistry

The removal efficiency (RE) and bioaerosol emission of a perlite biofilter treating vapors of toluene (T) and/or ethyl acetate (EA) were assessed, under different operating conditions, during 171 days. Under the first stages of operation, a mixture of EA and T was treated, with equivalent inlet loads (ILs) of each compound (ranging from 26 to 84 g m -3 h -1 ), achieving a 100% RE of EA, and a maximum elimination capacity (EC) of T of 58.7 g m -3 h -1 . An inhibition of T removal was noted in presence of EA, as T was treated subsequently to EA, along biofilter depth. A 17 days starvation period induced no global deterioration of performance regarding EA removal, but a 50% lower RE of T. Suspension of one contaminant, with interspersed feeding of only one component of the mixture, caused a permanent drop of the RE of EA (to 87.3%), after a T only feeding of 41 days. Flow cytometry (FC) was applied for quantification of bioaerosols, allowing for differentiation between viable, dead and damaged cells. During the overall biofilter operation, bioaerosol emission was not statistically different from bioaerosol retention. However, the biofilter significantly emitted bioaerosols (mostly viable cells) during start-up and IL increase, whereas a global retention of dead cells was observed during the interspersed feeding of one contaminant. Bioaerosols measured by FC (10 7 Cells m -3 ) were three orders of magnitude greater than with plate counting dishes, indicating that FC does not underestimate bioaerosols as culture dependent techniques.

Evaluation of bioaerosols by flow cytometry and removal performance in a biofilter treating toluene/ethyl acetate vapors.

Chemosphere

chemistry

Polyethylene (PE) agricultural soil films are easily embrittled and decomposed to microplastics (MPs) in environment. As widely used pesticides in vegetable farmland, carbendazim, dipterex, diflubenzuron, malathion, difenoconazole have potential environmental and human safety risks. They are often coexisting with MPs in the environment, and may cause consequential pollution to the ecosystem. Studying the adsorption behavior between pesticides and PE agricultural soil films MPs would be helpful for the risk assessment of co-exposure of pesticides and MPs. Herein, a systematic study on batch adsorption experiments was performed to determine the adsorption process of pesticides on MPs, the environmental factors on adsorption capacity were evaluated, and the adsorption mechanisms were discussed. Results suggested that all these five pesticides can adsorb on MPs, especially for diflubenzuron and difenoconazole. The adsorption kinetics and isotherm fitted to the Pseudo-second-order and Freundlich model, respectively, indicating that besides the adsorption onto surface sites, mass transfer and intraparticle diffusion were involved in the adsorption process, and the adsorption process was mostly controlled by physical and chemical interactions. The adsorption amounts of 5 pesticides on PE MPs follow the order of DIF > DIFE > MAL > CAR > DIP with K F correlated positively with octanol-water partition coefficients (LogK ow ). The thermodynamic study indicates the adsorption of all pesticides as spontaneous and exothermic processes. The results of this study illustrated that PE MPs can be a good carrier of pesticides in agricultural field.

Adsorption behavior and mechanism of five pesticides on microplastics from agricultural polyethylene films.

Chemosphere

chemistry

Madín Reservoir provides a substantial amount of drinking water to two municipalities close to Mexico City metropolitan area. However, it receives untreated wastewater discharges from domestic sources in the towns of Nuevo Madín and others, as well as diverse pollutants which are hauled by the Río Tlalnepantla from its upper reaches, so that the xenobiotics in the reservoir are highly diverse in terms of type and quantity. Previous studies showed that MR is contaminated with xenobiotics such as Al, Hg and Fe, as well as NSAIDs, at concentrations exceeding the limits established for aquatic life protection. These pollutants have been shown to induce oxidative stress on Cyprinus carpio and may therefore also damage the genetic material of exposed organisms, eliciting cytotoxicity as well. The present study aimed to determine the genotoxicity and cytotoxicity induced on blood, liver and gill of C. carpio by the pollutants present in MR water. Specimens were exposed to water from five sampling sites and the following biomarkers were evaluated: DNA damage by comet assay, frequency of micronuclei, apoptosis by TUNEL assay and caspase-3 activity. Significant increases relative to the control group (P < 0.05) were found with all biomarkers in all tissues evaluated, with the level of damage differing between sampling sites. In conclusion, pollutants present in MR water are genotoxic and cytotoxic to C. carpio, and this sentinel species, coupled with the biomarkers evaluated herein, is a reliable tool for assessing the health risk to wildlife posed by exposure to pollutants in freshwater bodies.

DNA damage and cytotoxicity induced on common carp by pollutants in water from an urban reservoir. Madín reservoir, a case study.

Chemosphere

chemistry

Pine needle samples were collected near a municipal solid waste incinerator (MSWI) in Pearl River Delta, southern China, as well as the stack gas and dust samples of the MSWI were simultaneously collected. Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) were analyzed following the USEPA Method 1613B. The concentration of PCDD/Fs in the pine needles (137-625 ng/kg, 25-51 ng I-TEQ/kg) is the highest level ever detected in China. Congener profile comparison and principal component analysis (PCA) confirmed the MSWI as an important emission source of environmental PCDD/Fs. The PCDD/Fs in the pine needles mainly depended on the atmospheric concentration, exposure time and also the wind direction. The accumulation of PCDD/Fs in this species did not occur at a steady rate, and the total concentrations covered up the actual photolysis information. Gas-phase partitioning of compounds in the atmosphere was the dominant process through which PCDD/Fs were adsorbed onto the pine needle surface in contrast with particle-phase deposition, and subsequent environmental behavior varied between the congeners. Photo-degradation was the major transformation process as PCDD/Fs were adsorbed onto the pine needle surfaces. Higher chlorinated PCDD/Fs were more recalcitrant to photo-degradation than those that were less chlorinated, and PCDDs were more resistant to photo-degradation than PCDFs. On the other hand, the strong ability of lipid-rich pine needles to accumulate dioxin compounds indicates they can be used as the absorption sink of PCDD/Fs in heavily polluted areas because it is easier to dispose of pine needles than it is to clean contaminated air.

Characteristic accumulation of PCDD/Fs in pine needles near an MSWI and emission levels of the MSWI in Pearl River Delta: A case study.

Chemosphere

chemistry

As a marine mammal species that inhabits shallow nearshore waters, humpback dolphins are likely exposed to a wide range of pollutants from adjacent land-based activities. Increased mortality rates of Australian humpback dolphins (Sousa sahulensis) in waters off a major urbanised centre triggered investigations into the threats to these species, including their contaminant exposure. The present study utilised archived tissues from 6 stranded animals to screen for a range of pollutants (PCDD/Fs, PBDEs, PCBs, organochlorine pesticides, PAHs, organotins, essential and non-essential elements) to inform future biopsy based biomonitoring strategies. Concentrations of PCBs and DDXs in blubber of some of these animals were remarkably high, at levels near or above toxicological thresholds associated with immune- and reproductive toxicity or population declines in other marine mammals. PBDEs, PAHs, HCB, organotins, 'drins' as well as other organic pesticides were not detected, or present at relatively low concentrations. Profiles of elements were similar in epidermis compared to other tissues, and apart from some exceptions (e.g. Fe, Cr, Co, Cu) their concentrations fell within 25th-75th percentiles of cetacean baselines in four of the five animals. Non-essential elements (Al, V, Pb, Ba, Ni, Cd) were notably elevated in one specimen which may have experienced poor health or nutritional status. These data provide a first insight into the contaminant status of a rare and poorly studied population inhabiting an urbanised area. The results highlight a need for future biomonitoring of live populations, and inform on priorities in the typically limited blubber and skin sample volumes obtained through biopsies.

Screening of organic and metal contaminants in Australian humpback dolphins (Sousa sahulensis) inhabiting an urbanised embayment.

Chemosphere

chemistry

Influence of land use type and urbanization level on the distribution of pharmaceuticals and personal care products (PPCPs) from the developed regions of Beijing-Tianjin-Hebei in the northern China was evaluated. The seasonal and spatial variations of the 22 target PPCPs were analyzed in the 63 sampling sites along the whole Beiyun River Basin. Results showed that the total PPCPs concentration had a wide variation range, from 132 ng L -1 to 25474 ng L -1 . Spatial interpolation analysis showed that agricultural land presented higher PPCPs contamination level than build-up land (p < 0.05) and the concentration was negatively correlated with urbanization level. Source apportionment showed the untreated sewage source contributed to 34%-53% of the PPCPs burden in the Beiyun River. Risk assessment indicated that diethyltoluamide, carbamazepine, octocrylene, gemfibrozil and triclocarban had high risks (RQ > 1), and small tributaries had the highest mixed risk (MRQ = 34). Species sensitivity distribution combined with the safety threshold method showed that PPCPs would have potential risk on aquatic organisms even at very low concentrations and triclocarban posed the highest risk in the Beiyun River.

Influence of land use type and urbanization level on the distribution of pharmaceuticals and personal care products and risk assessment in Beiyun River, China.

Chemosphere

chemistry

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous organic contaminants, which are found in soils throughout the U.S. The objective of this study was to determine the background concentrations, distributions, and sources of 16 USEPA priority PAHs in two urban soils. A total of 114 soil samples were collected from two large cities in Florida: Orlando and Tampa. The results showed that soils were dominated by high molecular weight PAHs in both cities. The average ∑16-PAHs in Orlando and Tampa soils were 3227 and 4562 μg kg -1 , respectively. The averages of 7 carcinogenic PAHs based on the benzo[a]pyrene-equivalent (BaP-EQ) concentrations in the two cities were 452 and 802 μg kg -1 . BaP-EQ concentrations in 60-62% of samples were higher than the Florida Soil Cleanup Target Level (FSCTL) for residential soils at 100 μg kg -1 and 20-25% of samples were higher than FSCTL for industrial soils at 700 μg kg -1 . Based on molecular diagnostic ratios and PMF modeling, major sources of soil PAHs in both cities were similar, mainly from pyrogenic sources including vehicle emissions, and biomass and coal combustion. Based on ArcGIS mapping, PAH concentrations in soils near business districts and high traffic roads were higher. Thus, it is important to consider background PAH concentrations in urban soils when considering soil remediation.

PAHs in urban soils of two Florida cities: Background concentrations, distribution, and sources.

Chemosphere

chemistry

It is stubborn to remove the lowly concentrated phthalic acid esters (PAEs) that usually coexist with other highly concentrated but low-toxic pollutants in municipal sewage. Herein, we report a novel strategy for completely removing the PAEs over a bi-functional {001}TiO 2 surface (with highly exposed {001} facet), which not only serve as functional sites to specifically adsorb the target PAEs pollutants, but also contribute to an enhanced oxidation ability. The adsorption behavior of PAEs on {001}TiO 2 is analyzed deeply through kinetic experiments combining with in situ ATR-FTIR spectroscopy and theoretical calculations. The results reveal that the adsorption capacities of PAEs on {001}TiO 2 are about 4-5 times higher than that on TiO 2 , both of which follow the pseudo-second-order and Langmuir model. This is mainly attributed to the interfacial Lewis Acid-Base Pair between {001} facet Ti 5c sites and CO of PAEs. Benefitting from the specific adsorption capability toward target pollutant and enhanced oxidation ability of {001} facets, nearly 100% of DMP or DEP in simulated wastewater can be eliminated by {001}TiO 2 within 2 h illumination, and the relevant degradation rate constants (k) (3.67 h -1 for DMP and 2.19 h -1 for DEP) are 5.73 and 3.08 folds higher than that of pure TiO 2 , respectively. In the application of municipal wastewater, nearly 76% of DMP and 85% DEP can be eliminated by {001}TiO 2 within 2 h illumination, which are nearly 3-6 fold higher than that of pure TiO 2 .

Efficient photocatalytic removal of phthalates easily implemented over a bi-functional {001}TiO2 surface.

Chemosphere

chemistry

This is the first study to investigate the reduction mechanism of Tl (III) to Tl(I) in the presence of plants, especially rice. Smaller plant density could effectively reduce the content of organic acids in the hydroponic system to keep the stability of Tl(III). As the plant density was reduced from 40 seedlings to 10 seedlings in 100 mL Tl(III) solution, the content of oxalate was declined to one-third of the original, and the ratio of Tl(III)/total Tl was increased from 39.6% to 81.0% in the first 2 h treatment. Then the differences in antioxidant capacity of rice exposed to the two Tl species were studied. The contents of malondialdehyde (MDA), hydrogen peroxide (H 2 O 2 ) and superoxide anion (O 2 ˙ - ) of rice roots exposed to Tl(III) were all higher than those to Tl(I). Meanwhile, the catalase (CAT) activity was significantly depressed and peroxidase (POD) was increased by Tl(III), whereas superoxide dismutase (SOD) showed a rise in both Tl(I) and Tl(III) with no significant difference between them. The expression of metallothionein gene OsMT1a to Tl(I) was upregulated to 255.5 times of Tl(III) though OsMT2c was downregulated to 0.39 times of Tl(III). Overall, the different responses in metallothionein gene expression and antioxidative enzyme activation might result in more ROS accumulation to rice roots by Tl(III) treatment than those by Tl(I).

Different responses in metallothionein gene expression and antioxidative enzyme activity lead to more ROS accumulation in rice exposed to Tl(III) than to Tl(I).

Chemosphere

chemistry

Biochar amendment in soil has the potential to sequester carbon, improve soil quality and mitigate greenhouse gas (GHG) emission in agriculture, but the impact of biochar amendments on dissolved organic matter (DOM) properties of soils in the fertilized agro-ecosystem has received little research attention. This study performed a long-term field experiment to assess the influence of biochar amendments (different addition rate: 4 t ha -1 and 8 t ha -1 ) on DOM characteristics in soils in wheat-maize rotation system in Loess Plateau of China by exploiting fluorescence excitation-emission spectrophotometry and parallel factor analysis (EEM-PARAFAC). Our results showed that the content of soil DOM was significantly influenced by the addition of biochar, and the higher biochar addition markedly increased the mean concentration of dissolved organic carbon (DOC) (from 83.99 mg kg -1 to 144.27 mg kg -1 ) in soils under the same fertilizer application. Three identified fluorescent components (fulvic acid-like, humic acid-like and tryptophan-like) were found, and fluorescence intensity of those components (especially humic-like material) was enhanced with the increasing DOC in the biochar treatments but the composition of DOM was not changed. These findings would be beneficial to understand the biochar's effects and processes in decreasing GHG emissions from soils.

Impacts of biochar addition on soil dissolved organic matter characteristics in a wheat-maize rotation system in Loess Plateau of China.

Chemosphere

chemistry

Phenanthrene can easily be absorbed into the plant from the soil and cannot be effectively degraded in it. Thus, it is greatly hazardous for food safety and human health. In our study, the biodegradability and remediation mechanism of endophytic fungus Phomopsis liquidambaris on phenanthrene in vivo of rice (Oryza sativa L.) was detected. The results showed that the fungus could successfully establish a symbiotic relationship with rice, thus had the potential to degrade phenanthrene absorbed into the plant. Changes of phenanthrene-degrading genes of fungus in the combined system were consistent with the trends of their corresponding enzymatic activities, and the phenanthrene-degrading enzyme activities and gene expression levels in roots of rice were higher than those in the shoot. Moreover, the combined system can enhance bioremediation by increasing root viability, chlorophyll content, and energy supply. The combined system had also significantly increased the PPO activity and SOD activity in shoot compared with the control treatment, while decreased the content of MDA when remediation in vivo. The study on the degradation mechanism of the combined system will help us to increase the practical application potential of endophyte to effectively repair contamination absorbed into plant seedlings.

Remediation mechanism of endophytic fungus Phomopsis liquidambaris on phenanthrene in vivo.

Chemosphere

chemistry

Technosols created to reclaim degraded soils is a promising solution that needs further research. The objectives of the study were: i) to create a Technosol with a very high capacity to immobilize copper from mining, ii) to assess the capacity of the Technosol to immobilize copper after planting two tropical native tree species, and iii) to analyse the capacity of the native trees for extracting copper from polluted soils. Myracrodruon urundeuva (aroeira) and Cedrela fissilis (pink cedar) were planted in pots with Technosol spiked with copper at concentrations of 125, 1525 and 3050 mg Cu kg -1 . Height and stem diameter were measured over 90 days. Biomass and Cu concentration in leaves, stem and roots were determined. Copper was analysed in soils by sequential extraction, as well as in leached water. The Technosol showed a very high capacity to immobilize copper, since 60-80% of the added copper was strongly retained in the soil, mainly by bentonite and carbonates. The Technosol with trees showed the same capacity to immobilize copper as the control, since concentration in shoots was higher than 300 mg Cu kg -1 and concentration in roots was even higher. These results show that Technosol and both species are useful tools to immobilize copper in polluted soils. Further studies are necessary to determine the total capacity of these trees to immobilize and/or extract copper in the long term and under field conditions.

The potential of a Technosol and tropical native trees for reclamation of copper-polluted soils.

Chemosphere

chemistry

Covalent-immobilization of the laccase enzyme onto the iron oxide nanoparticles was achieved using N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDAC) as cross-linkers. The presence of sulphur moeity in the laccase immobilized nanoparticles (LNPs) observed through Scanning Electron Microscopy- Energy dispersive X-ray spectroscopy (SEM-EDS) spectra confirmed the immobilization of laccase enzyme. The TEM analysis of iron oxide nanoparticles (FNPs), chitosan coated iron nanoparticles (CNPs) and laccase immobilized nanoparticles (LNPs) confirmed their sizes around 12, 15 and 20 nm, respectively. The effect of LNPs in degrading chlorpyrifos under field conditions was studied by simulating the conditions in a column. Column A, which was used as control showed more leaching of chlorpyrifos as compared to column B containing LNPs. The sorption coefficient (K d ) value obtained for control (column A) and LNPs containing column B were 21.6 and 112.3 L/kg, respectively. LNPs altered the K d values of soil thereby showing lesser leaching potential. Higher the K d value, lesser will be the leaching potential in the ground water. Copper in laccase enzyme resulted in hydrolysis of chlorpyrifos. Chitosan used for coating on FNPs and soil organic matter resulted in the adsoption of chlorpyrifos. Current results will allow a better assessment of the role of LNPs as a competent deterrent in chlorpyrifos mobility and degradation.

Degradation of chlorpyrifos in soil using laccase immobilized iron oxide nanoparticles and their competent role in deterring the mobility of chlorpyrifos.

Chemosphere

chemistry

A new combined solar plant including an annular continuous-flow compound parabolic collector (CPC) reactor and a pasteurization system was designed, built, and tested for simultaneous drinking water disinfection and chemical decontamination. The plant did not use pumps and had no electricity costs. First, water continuously flowed through the CPC reactor and then entered the pasteurizer. The temperature and water flow from the plant effluent were controlled by a thermostatic valve located at the pasteurizer outlet that opened at 80 °C. The pasteurization process was simulated by studying the effect of heat treatment on the death kinetic parameters (D and z values) of Escherichia coli K12 (CECT 4624). 99.1% bacteria photo-inactivation was reached in the TiO 2 -CPC system (0.60 mg cm -2 TiO 2 ), and chemical decontamination in terms of antipyrine degradation increased with increasing residence time in the TiO 2 -CPC system, reaching 70% degradation. The generation of hydroxyl radicals (between 100 and 400 nmol L -1 ) was a key factor in the CPC system efficiency. Total thermal bacteria inactivation was attained after pasteurization in all cases. Chemical degradation and bacterial photo-inactivation in the TiO 2 -CPC system were improved with the addition of 150 mg L -1 of H 2 O 2 , which generated approximately 2000-2300 nmol L -1 of HO ● radicals. Finally, chemical degradation and bacterial photo-inactivation kinetic modelling in the annular CPC photoreactor were evaluated. The effect of the superficial liquid velocity on the overall rate constant was also studied. Both antipyrine degradation and E. coli photo-inactivation were found to be controlled by the catalyst surface reaction rate.

A novel combined solar pasteurizer/TiO2 continuous-flow reactor for decontamination and disinfection of drinking water.

Chemosphere

chemistry

Cadmium (Cd) is among the most widespread toxic trace elements found in agricultural soils due to various anthropogenic activities. The role of micronutrient-amino chelates on reducing Cd toxicity in crop plants is recently introduced. The current study was conducted to highlight the role of foliar application of zinc-lysine (Zn-lys) complex on biochemical and growth parameters and Cd uptake in wheat (Triticum aestivum) grown in aged Cd-contaminated soil. Foliar concentration of Zn-lys (0, 10, 20, and 30 mg L -1 ) was applied at different time intervals (2nd, 3rd, 5th and 7th week of sowing) and plants were harvested at maturity. Folliar application of Zinc-lys significantly increased the photosynthesis, grain yield, enzyme activities and Zn contents in different plant tissues. Zinc-lys reduced Cd contents in grains, shoot and root as well as reduced the oxidative stress in wheat linearly in a dose-additive manner. Taken together, Zn-lys chelate efficiently improved wheat growth and fortified Zn contents while reduced Cd concentration in plant in a Zn-deficient Cd-contaminated soil. Although, health risk index (HRI) from the soil sampling area seems to be lower than <1 for Cd but may exceed due to long-term consumption of grains produced from such contaminated soil. Foliar applied Zn-lys reduced HRI which may help to reduce health risks associated with Cd.

Effect of zinc-lysine on growth, yield and cadmium uptake in wheat (Triticum aestivum L.) and health risk assessment.

Chemosphere

chemistry

Microbial fuel cells (MFCs) are an emerging technology for converting organic waste into electricity, thus providing potential solution to energy crises along with eco-friendly wastewater treatment. The electrode properties and biocatalysts are the major factors affecting electricity production in MFC. The electrons generated during microbial metabolism are captured by the anode and transferred towards the cathode via an external circuit, causing the flow of electricity. This flow of electrons is greatly influenced by the electrode properties and thus, much effort has been made towards electrode modification to improve the MFC performance. Different semiconductors, nanostructured metal oxides and their composite materials have been used to modify the anode as they possess high specific surface area, good biocompatibility, chemical stability and conductive properties. The cathode materials have also been modified using metals like platinum and nano-composites for increasing the redox potential, electrical conductivity and surface area. Therefore, this paper reviews the recent developments in the modification of electrodes towards improving the power generation capacity of MFCs.

Advances in the development of electrode materials for improving the reactor kinetics in microbial fuel cells.

Chemosphere

chemistry

The design and synthesis of uranium sorbent materials with high uptake efficiency, capacity and selectivity, as well as excellent hydrolytic stability and radiation resistance remains a challenge. Herein, a polyoxometalate (POM)-organic framework material (SCU-19) with a rare inclined polycatenation structure was designed, synthesized through a solvothermal method, and tested for uranium separation. Under dark conditions, SCU-19 can efficiently capture uranium through ligand complexation using its exposed oxo atoms and partial chemical reduction from U VI to U IV by the low-valent Mo atoms in the POM. An additional U VI photocatalytic reduction mechanism can occur under visible light irradiation, leading to a higher uranium removal without saturation and faster sorption kinetics. SCU-19 is the only uranium sorbent material with three distinct sorption mechanisms, as further demonstrated by X-ray photoelectron spectroscopy (XPS) and X-ray absorption near edge structure (XANES) analysis.

Three Mechanisms in One Material: Uranium Capture by a Polyoxometalate-Organic Framework through Combined Complexation, Chemical Reduction, and Photocatalytic Reduction.

Angewandte Chemie (International ed. in English)

chemistry

A palladium-catalyzed cascade reaction based on the trapping of transient alkyl-Pd II intermediates with arynes encompassing a C-H activation step has been developed. This synthetic pathway gives rise to hetero-spirocyclic scaffolds containing a biaryl motif, and opens up new synthetic strategies in the design of cascade reactions since it gathers several aspects of Pd chemistry, i.e., intra- and intermolecular carbopalladation of unsaturated species, C-H activation and C-C coupling processes.

Trapping σ-Alkyl-Palladium(II) Intermediates with Arynes Encompassing Intramolecular C-H Activation: Spirobiaryls through Pd-Catalyzed Cascade Reactions.

Angewandte Chemie (International ed. in English)

chemistry

Nanomaterials offer exciting properties and functionalities. However, their production and processing frequently involve complex methods, cumbersome equipment, harsh conditions, and hazardous media. The capability of organisms to accomplish this using mild conditions offers a sustainable, biocompatible, and environmentally friendly alternative. Different nanomaterials such as metal nanoparticles, quantum dots, silica nanostructures, and nanocellulose are being synthesized increasingly through living entities. In addition, the bionanofabrication potential enables also the in situ processing of nanomaterials inside biomatrices with unprecedented outcomes. In this Minireview we present a critical state-of-the-art vision of current nanofabrication approaches mediated by living entities (ranging from unicellular to higher organisms), in order to expand this knowledge and scrutinize future prospects. An efficient interfacial interaction at the nanoscale by green means is within reach through this approach.

Synthesis and Processing of Nanomaterials Mediated by Living Organisms.

Angewandte Chemie (International ed. in English)

chemistry

Affinity-based protein profiling (AfBPP) is a widely applied method for the target identification of bioactive molecules. Probes containing photocrosslinkers, such as benzophenones, diazirines, and aryl azides, irreversibly link the molecule of interest to its target protein upon irradiation with UV light. Despite their prevalent application, little is known about photocrosslinker-specific off-targets, affecting the reliability of results. Herein, we investigated background protein labeling by gel-free quantitative proteomics. Characteristic off-targets were identified for each photoreactive group and compiled in a comprehensive inventory. In a proof-of-principle study, H8, a protein kinase A inhibitor, was equipped with a diazirine moiety. Application of this photoprobe revealed, by alignment with the diazirine background, unprecedented insight into its in situ proteome targets. Taken together, our findings guide the identification of biologically relevant binders in photoprobe experiments.

A Whole Proteome Inventory of Background Photocrosslinker Binding.

Angewandte Chemie (International ed. in English)

chemistry

The decomposition of state-of-the-art lithium ion battery (LIB) electrolytes leads to a highly complex mixture during battery cell operation. Furthermore, thermal strain by e.g., fast charging can initiate the degradation and generate various compounds. The correlation of electrolyte decomposition products and LIB performance fading over life-time is mainly unknown. The thermal and electrochemical degradation in electrolytes comprising 1 m LiPF 6 dissolved in 13 C 3 -labeled ethylene carbonate (EC) and unlabeled diethyl carbonate is investigated and the corresponding reaction pathways are postulated. Furthermore, a fragmentation mechanism assumption for oligomeric compounds is depicted. Soluble decomposition products classes are examined and evaluated with liquid chromatography-high resolution mass spectrometry. This study proposes a formation scheme for oligo phosphates as well as contradictory findings regarding phosphate-carbonates, disproving monoglycolate methyl/ethyl carbonate as the central reactive species.

Clarification of Decomposition Pathways in a State-of-the-Art Lithium Ion Battery Electrolyte through 13 C-Labeling of Electrolyte Components.

Angewandte Chemie (International ed. in English)

chemistry

The adhesive system of mussels evolved into a powerful and adaptive system with affinity to a wide range of surfaces. It is widely known that thereby 3,4-dihydroxyphenylalanine (Dopa) plays a central role. However underlying binding energies remain unknown at the single molecular scale. Here, we use single-molecule force spectroscopy to estimate binding energies of single catechols with a large range of opposing chemical functionalities. Our data demonstrate significant interactions of Dopa with all functionalities, yet most interactions fall within the medium-strong range of 10-20 kB T. Only bidentate binding to TiO2 surfaces exhibits a higher binding energy of 29 kB T. Our data also demonstrate at the single-molecule level that oxidized Dopa and amines exhibit interaction energies in the range of covalent bonds, confirming the important role of Dopa for cross-linking in the bulk mussel adhesive. We anticipate that our approach and data will further advance the understanding of biologic and technologic adhesives.

Resolving Non-Specific and Specific Adhesive Interactions of Catechols at Solid/Liquid Interfaces at the Molecular Scale.

Angewandte Chemie (International ed. in English)

chemistry

The experimental detection and synthesis of pentazole (HN 5 ) and its anion (cyclo-N 5 - ) have been actively pursued for the past hundred years. The synthesis of an aesthetic three-dimensional metal-pentazolate framework (denoted as MPF-1) is presented. It consists of sodium ions and cyclo-N 5 - anions in which the isolated cyclo-N 5 - anions are preternaturally stabilized in this inorganic open framework featuring two types of nanocages (Na 20 N 60 and Na 24 N 60 ) through strong metal coordination bonds. The compound MPF-1 is indefinitely stable at room temperature and exhibits high thermal stability relative to the reported cyclo-N 5 - salts. This finding offers a new approach to create metal-pentazolate frameworks (MPFs) and enables the future exploration of interesting pentazole chemistry and also related functional materials.

Stabilization of the Pentazolate Anion in a Zeolitic Architecture with Na20 N60 and Na24 N60 Nanocages.

Angewandte Chemie (International ed. in English)

chemistry

Novel targets are needed for treatment of devastating diseases such as cancer. For decades, natural products have guided innovative therapies by addressing diverse pathways. Inspired by the potent cytotoxic bioactivity of myxobacterial vioprolides A-D, we performed in-depth studies on their mode of action. Based on its prominent potency against human acute lymphoblastic leukemia (ALL) cells, we conducted thermal proteome profiling (TPP) and deciphered the target proteins of the most active derivative vioprolide A (VioA) in Jurkat cells. Nucleolar protein 14 (NOP14), which is essential in ribosome biogenesis, was confirmed as a specific target of VioA by a suite of proteomic and biological follow-up experiments. Given its activity against ALL cells compared to healthy lymphocytes, VioA exhibits unique therapeutic potential for anticancer therapy through a novel mode of action.

The Cytotoxic Natural Product Vioprolide A Targets Nucleolar Protein 14, Which Is Essential for Ribosome Biogenesis.

Angewandte Chemie (International ed. in English)

chemistry

An asymmetric catalytic decarboxylative [4+2] annulation of 4-ethynyl dihydrobenzooxazinones and carboxylic acids has been established by cooperative copper and nucleophilic Lewis base catalysis. A C1 ammonium enolate and copper-allenylidene complex, each catalytically generated from different substrates, underwent a cascade asymmetric propargylation and lactamization process to yield optically active 3,4-dihydroquinolin-2-one derivatives with excellent levels of stereoselectivity (up to 99 % ee, 95:5 d.r.).

Asymmetric [4+2] Annulation of C1 Ammonium Enolates with Copper-Allenylidenes.

Angewandte Chemie (International ed. in English)

chemistry

A series of tamoxifen-like metallocifens of the group-8 metals (Fe, Ru, and Os) has strong antiproliferative activity on the triple-negative breast cancer cells (MDA-MB-231). To shed light on the mechanism of action of these molecules, synchrotron radiation X-ray fluorescence nanoimaging studies were performed on cells exposed to osmocenyl-tamoxifen (Oc-OH-Tam) to disclose its intracellular distribution. High-resolution mapping of the lipophilic Oc-OH-Tam in cells revealed its preferential accumulation in the endomembrane system. This is consistent with the ability of the amino nitrogen chain of the compounds to be protonated at physiological pH and responsible for electrostatic interactions between Oc-OH-Tam and membranes. A comprehensive scenario is proposed that provides new insight into the cellular behavior and activation of Oc-OH-Tam and advances the understanding of its mechanism of action.

Intracellular Localization of an Osmocenyl-Tamoxifen Derivative in Breast Cancer Cells Revealed by Synchrotron Radiation X-ray Fluorescence Nanoimaging.

Angewandte Chemie (International ed. in English)

chemistry

In reactions restricted previously to a ruthenium catalyst, a 1-lithium-2-alkyl-1,2-dihydropyridine complex is shown to be a competitive alternative dehydrogenation catalyst for the transformation of diamine boranes into cyclic 1,3,2-diazaborolidines, which can in turn be smoothly arylated in good yields. This study established the conditions and solvent dependence of the catalysis through NMR monitoring, with mechanistic insight provided by NMR (including DOSY) experiments and X-ray crystallographic studies of several model lithio intermediates.

Lithium Dihydropyridine Dehydrogenation Catalysis: A Group 1 Approach to the Cyclization of Diamine Boranes.

Angewandte Chemie (International ed. in English)

chemistry

Atomically dispersed and nitrogen coordinated single metal sites (M-N-C, M=Fe, Co, Ni, Mn) are the popular platinum group-metal (PGM)-free catalysts for many electrochemical reactions. Traditional wet-chemistry catalyst synthesis often requires complex procedures with unsatisfied reproducibility and scalability. Here, we report a facile chemical vapor deposition (CVD) strategy to synthesize the promising M-N-C catalysts. The deposition of gaseous 2-methylimidazole onto M-doped ZnO substrates, followed by an in situ thermal activation, effectively generated single metal sites well dispersed into porous carbon. In particular, an optimal CVD-derived Fe-N-C catalyst exclusively contains atomically dispersed FeN 4 sites with increased Fe loading relative to other catalysts from wet-chemistry synthesis. The catalyst exhibited outstanding oxygen-reduction activity in acidic electrolytes, which was further studied in proton-exchange membrane fuel cells with encouraging performance.

Chemical Vapor Deposition for Atomically Dispersed and Nitrogen Coordinated Single Metal Site Catalysts.

Angewandte Chemie (International ed. in English)

chemistry

Here, we provide the first structural characterization of host-guest complexation between cucurbit[7]uril (Q7) and dimethyllysine (KMe 2 ) in a model protein. Binding was dominated by complete encapsulation of the dimethylammonium functional group. While selectivity for the most sterically accessible dimethyllysine was observed both in solution and in the solid state, three different modes of Q7-KMe 2 complexation were revealed by X-ray crystallography. The crystal structures revealed also entrapped water molecules that solvated the ammonium group within the Q7 cavity. Remarkable Q7-protein assemblies, including inter-locked octahedral cages that comprise 24 protein trimers, occurred in the solid state. Cucurbituril clusters appear to be responsible for these assemblies, suggesting a strategy to generate controlled protein architectures.

Cucurbit[7]uril-Dimethyllysine Recognition in a Model Protein.

Angewandte Chemie (International ed. in English)

chemistry

We present a novel route for the quick and easy synthesis of a broad range of β-lactams. The synthesis involves a [3+1] cyclization of amide dianions with diiodomethane. In contrast to the seminal work of Hirai et al. from 1979, the reaction proved to be a general and efficient approach towards azetidinones. The ease of the process was confirmed by DFT calculations and its power demonstrated by a diversity-oriented synthesis of β-lactams with four points of diversity determined by the choice of Ugi adducts as starting materials.

β-Lactam Synthesis through Diodomethane Addition to Amide Dianions.

Angewandte Chemie (International ed. in English)

chemistry

Racemic 3,4-dihydro-2H-pyrroles, hypothetical intermediates of the Barton-Zard reaction, were synthesized in a highly diastereoselective manner and fully characterized for the first time. Kinetic resolution of the dihydropyrroles with a quinine-derived thiourea afforded the (+)-3-arylpyrrole products and recovered (+)-3,4-dihydro-2H-pyrroles with high efficiency (s-factor up to 153). The resolved (+)-3,4-dihydro-2H-pyrroles underwent subsequent aromatization with a quinidine-derived thiourea catalyst to afford (-)-3-arylpyrroles with excellent central-to-axial chirality transfer. In contrast to the well-accepted Barton-Zard mechanism, the aromatization of the 3,4-dihydro-2H-pyrroles in the presence of a bifunctional catalyst is believed to proceed by an unprecedented sequence involving syn elimination of HNO 2 and aromatization.

Catalytic Kinetic Resolution by Enantioselective Aromatization: Conversion of Racemic Intermediates of the Barton-Zard Reaction into Enantioenriched 3-Arylpyrroles.

Angewandte Chemie (International ed. in English)

chemistry

Finely controlled circularly polarized luminescence (CPL) supramolecular polymerization based on a tetraphenylethene core with four l- or d-alanine branch side chains (l-1 and d-1) in the solution state is presented, resulting from the tuning of mechanical stimulus. Weak, green emissions of l-1 and d-1 in tetrahydrofuran (THF) were converted into strong blue emissions by tuning the mechanical stimulus. The strong blue emissions were caused by an aggregation-induced emission (AIE) effect during the formation of a supramolecular polymer. Lag time in the supramolecular polymerization was drastically reduced by the mechanical stimulus, which was indicative of the acceleration of the supramolecular polymerization. A significant enhancement of circular dichroism (CD) and CPL signals of l-1 and d-1 was observed by tuning the rotational speed of the mechanical stimulus, implying that the chiral supramolecular polymerization was accelerated by the mechanical stimulus.

Finely Controlled Circularly Polarized Luminescence of a Mechano-Responsive Supramolecular Polymer.

Angewandte Chemie (International ed. in English)

chemistry

Among the variety of isolable compounds with multiple bonds involving silicon, examples of compounds that contain silicon-boron double bonds (borasilenes) still remain relatively rare. Herein, we report the synthesis of the potassium salt of a chloride adduct of borasilene 1 ([2] - ), which was obtained as an orange crystalline solid. Single-crystal X-ray diffraction analysis and reactivity studies on [2] - confirmed the double-bond character of the Si=B bond as well as the reduced Lewis acidity, which is due to the coordination of Cl - to the boron center. A thermal reaction of [2] - afforded a bicyclic product by formal intramolecular C-H insertion across the Si=B bond of 1, which was corroborated by a theoretical study.

An Isolable Potassium Salt of a Borasilene-Chloride Adduct.

Angewandte Chemie (International ed. in English)

chemistry

In a novel process, CO 2 and CH 4 from the off-gases of the coke oven and blast furnace are used in homogeneous reforming of those greenhouse gases to valuable syngas, a mixture of H 2 and CO. Synthetic mixtures of the off-gases from those large apparatuses of steel industry are fed to a high-temperature, high-pressure flow reactor at varying temperature, pressure, residence time, and mixing ratio of coke oven gas (COG) to blast furnace gas (BFG). In this study, a maximal reduction of 78.5 % CO 2 and a CH 4 conversion of 95 % could be achieved at 1350 °C, 5.5 bar, and a COG/BFG ratio of 0.6. Significant carbonaceous deposits were formed but did not block the reactor tube in the operational time window allowing cyclic operation of the process. These measurements were based on prior thermodynamic analysis and kinetic predictions using an elementary-step reaction mechanism.

Reduction of CO2 Emission from Off-Gases of Steel Industry by Dry Reforming of Methane.

Angewandte Chemie (International ed. in English)

chemistry

Electrocatalytic CO 2 reduction to value-added products provides a viable alternative to the use of carbon sources derived from fossil fuels. Carrying out these transformations at reasonable energetic costs, for example, with low overpotential, remains a challenge. Molecular catalysts allow fine control of activity and selectivity via tuning of their coordination sphere and ligand set. Herein we investigate a series of cobalt(III) pyridine-thiolate complexes as electrocatalysts for CO 2 reduction. The effect of the ligands and proton sources on activity was examined. We identified bipyridine bis(2-pyridinethiolato) cobalt(III) hexaflurophosphate as a highly selective catalyst for formate production operating at a low overpotential of 110 mV with a turnover frequency (TOF) of 10 s -1 . Electrokinetic analysis coupled with density functional theory (DFT) computations established the mechanistic pathway, highlighting the role of metal hydride intermediates. The catalysts deactivate via the formation of stable cobalt carbonyl complexes, but the active species could be regenerated upon oxidation and release of coordinated CO ligands.

Electroreduction of CO2 to Formate with Low Overpotential using Cobalt Pyridine Thiolate Complexes.

Angewandte Chemie (International ed. in English)

chemistry

Patients diagnosed with cancer commonly have a high degree of anxiety during an initial oncology consultation, which may interfere with a patient's ability to retain information required to make informed treatment decisions. A previous study randomised breast cancer survivors (volunteers) to view either (a) a brief video depicting a standard initial consultation from an oncologist or (b) an identical consultation with the addition of compassionate statements from the oncologist, and found the compassionate statements reduced anxiety among the volunteers. However, while compassionate statements reduced anxiety during simulation, it is currently unknown whether watching a video containing compassionate statements from an oncologist prior to an initial oncology consultation will reduce anxiety among patients referred to a cancer centre. The aim of this randomised control trial is to test whether watching a brief video containing compassionate statements from an oncologist, compared with watching a standard introduction video, prior to an initial oncology consultation will reduce the degree of anxiety among patients referred to a cancer centre. This is a prospective, randomised controlled clinical trial at an academic cancer centre. We will enrol adult patients scheduled for an initial oncology consultation. Subjects will be randomly assigned to receive a standard introduction video or enhanced compassion video for viewing prior to the initial oncology consultation. On arrival to the cancer centre, we will measure anxiety severity using the Hospital Anxiety and Depression Scale (HADS). The HADS has two 7-item subscales (HADS anxiety and HADS depression) and is well-validated among oncology patients. We will use Wilcoxon rank-sum test to test for a difference in the HADS subscales between the two video groups. The Cooper University Hospital Institutional Review Board approved this study. The results from this randomised control trial will be submitted for publication to a peer-reviewed journal. NCT04503681.

Preconsultation compassion intervention to reduce anxiety among patients referred to a cancer center: protocol for a randomised control trial.

BMJ open

medicine

Chronic post-surgical pain (CPSP) after lung or pleural surgery is a common complication and associated with a decrease in quality of life, long-term use of pain medication and substantial economic costs. An abundant number of primary prognostic factor studies are published each year, but findings are often inconsistent, methods heterogeneous and the methodological quality questionable. Systematic reviews and meta-analyses are therefore needed to summarise the evidence. The reporting of this protocol adheres to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) checklist. We will include retrospective and prospective studies with a follow-up of at least 3 months reporting patient-related factors and surgery-related factors for any adult population. Randomised controlled trials will be included if they report on prognostic factors for CPSP after lung or pleural surgery. We will exclude case series, case reports, literature reviews, studies that do not report results for lung or pleural surgery separately and studies that modified the treatment or prognostic factor based on pain during the observation period. MEDLINE, Scopus, Web of Science, Embase, Cochrane, CINAHL, Google Scholar and relevant literature reviews will be searched. Independent pairs of two reviewers will assess studies in two stages based on the PICOTS criteria. We will use the Quality in Prognostic Studies tool for the quality assessment and the CHARMS-PF checklist for the data extraction of the included studies. The analyses will all be conducted separately for each identified prognostic factor. We will analyse adjusted and unadjusted estimated measures separately. When possible, evidence will be summarised with a meta-analysis and otherwise narratively. We will quantify heterogeneity by calculating the Q and I 2 statistics. The heterogeneity will be further explored with meta-regression and subgroup analyses based on clinical knowledge. The quality of the evidence obtained will be evaluated according to the Grades of Recommendation Assessment, Development and Evaluation guideline 28. Ethical approval will not be necessary, as all data are already in the public domain. Results will be published in a peer-reviewed scientific journal. CRD42021227888.

Prognostic factors for chronic post-surgical pain after lung or pleural surgery: a protocol for a systematic review and meta-analysis.

BMJ open

medicine

Severe subjective psychosomatic symptoms (SPS) in adolescents are a major public health concern, and lifestyle modification interventions for reducing SPS are important topics. Recently, we developed a school-based lifestyle education involving parents for reducing SPS of adolescents (SPRAT), an improved version of the programme from our previous study Programme for adolescent of lifestyle education in Kumamoto (PADOK). This study aimed to evaluate the effectiveness of SPRAT in reducing SPS among adolescents. This is a 6-month, cluster randomised clinical trial with two intervention arms (SPRAT vs usual school education). The study population will be composed of middle school students (aged 12-14 years) with their parents/guardians in Japan. SPRAT is expected to be a more powerful programme than PADOK as it reinforces the role of parent participation. The primary endpoint will be the change from baseline SPS scores to those obtained after 6 months. Between-group differences will be analysed following the intention-to-treat principle. Crude and multivariate adjusted effects will be examined using a general linear mixed-effects model for continuous variables and a logistic regression model for dichotomous variables. The sample size required was determined based on the information needed to detect a difference in the primary outcome with a significance level of 5% and power of 80% under the assumptions of 40 students per cluster (assuming the same sample size for each cluster), an effect size of 0.3 and an intraclass correlation coefficient of 0.02. In total, participation by 28 schools (14 schools in each arm) (students: n=1120) will be needed. This study was approved by the Medical Ethical Committee of Minami Kyushu University in 2017 (number 137). The findings will be disseminated widely through peer-reviewed publications and conference presentations. UMIN000026715; Pre-results.

School-based lifestyle education involving parents for reducing subjective psychosomatic symptoms in Japanese adolescents: study protocol for a cluster randomised controlled trial.

BMJ open

medicine

To survey the healthcare professionals' background and experiences from work with patients with COVID-19 in intensive care units (ICUs) during the first wave of the COVID-19 pandemic in Norway. Observational cohort study. COVID-ICUs in 27 hospitals across Norway. Healthcare professionals (n=484): nurses (81%), medical doctors (9%) and leaders (10%), who responded to a secured, web-based questionnaire from 6 May 2020 to 15 July 2020. Healthcare professionals': (1) professional and psychological preparedness to start working in COVID-ICUs, (2) factors associated with high degree of preparedness and (3) experience of working conditions. The age of the respondents was 44.8±10 year (mean±SD), 78% were females, 92% had previous ICU working experience. A majority of the respondents reported professional (81%) and psychological (74%) preparedness for working in COVID-ICU. Factors significantly associated with high professional preparedness for working in COVID-19-ICU in a multivariate logistic model were previous ICU work experience (p < 0.001) and participation in COVID-ICU simulation team training (p<0.001). High psychological preparedness was associated with higher age (p=0.003), living with spouse or partner (p=0.013), previous ICU work experience (p = 0.042) and participation in COVID-ICU simulation team training (p=0.001). Working with new colleagues and new professional challenges were perceived as positive in a majority of the respondents, whereas 84% felt communication with coworkers to be challenging, 46% were afraid of being infected and 82% felt discomfort in denying access for patient relatives to the unit. Symptoms of sweating, tiredness, dehydration, headache, hunger, insecurity, mask irritation and delayed toilet visits were each reported by more than 50%. Healthcare professionals working during the first wave of COVID-ICU patients in Norway were qualified and prepared, but challenges and potential targets for future improvements were present. NCT04372056.

Healthcare professionals in COVID-19-intensive care units in Norway: preparedness and working conditions: a cohort study.

BMJ open

medicine

Malaria infection could result in severe disease with high mortality. Prognostic models and scores predicting severity of infection, complications and mortality could help clinicians prioritise patients. We conducted a systematic review to assess the various models that have been produced to predict disease severity and mortality in patients infected with malaria. A systematic review. Medline, Global health and CINAHL were searched up to 4 September 2019. Published articles on models which used at least two points (or variables) of patient data to predict disease severity; potential development of complications (including coma or cerebral malaria; shock; acidosis; severe anaemia; acute kidney injury; hypoglycaemia; respiratory failure and sepsis) and mortality in patients with malaria infection. Two independent reviewers extracted the data and assessed risk of bias using the Prediction model Risk Of Bias Assessment Tool. A total of 564 articles were screened and 24 articles were retained which described 27 models/scores of interests. Two of the articles described models predicting complications of malaria (severe anaemia in children and development of sepsis); 15 articles described original models predicting mortality in severe malaria; 3 articles described models predicting mortality in different contexts but adapted and validated to predict mortality in malaria; and 4 articles described models predicting severity of the disease. For the models predicting mortality, all the models had neurological dysfunction as a predictor; in children, half of the models contained hypoglycaemia and respiratory failure as a predictor meanwhile, six out of the nine models in adults had respiratory failure as a clinical predictor. Acidosis, renal failure and shock were also common predictors of mortality. Eighteen of the articles described models that could be applicable in real-life settings and all the articles had a high risk of bias due to lack of use of consistent and up-to-date methods of internal validation. Evidence is lacking on the generalisability of most of these models due lack of external validation. Emphasis should be placed on external validation of existing models and publication of the findings of their use in clinical settings to guide clinicians on management options depending on the priorities of their patients. CRD42019130673.

Prognostic models for the clinical management of malaria and its complications: a systematic review.

BMJ open

medicine

To examine associations of behavioural risk factors, namely cigarette smoking, physical activity, dietary intakes and alcohol consumption, with blood lipids profile. Data drawn from a cross-sectional study involving participants aged 18 years and over (n=363) from the nationwide WHO STEPwise Nutrition and Non-communicable Disease Risk Factor survey in Lebanon. Demographic characteristics, behaviours and medical history were obtained from participants by questionnaire. Dietary assessment was performed using a 61-item Culture-Specific Food Frequency Questionnaire that measured food intake over the past year. Lipid levels were measured by the analysis of fasting blood samples (serum total cholesterol (TC), triglycerides (TG), very low-density lipoprotein (VLDL), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C)). Current cigarette smoking, alcohol consumption and low physical activity were prevalent among 33.3%, 39.7% and 41.6% of the sample, respectively. The contributions of fat and saturated fat to daily energy intake were high, estimated at 36.5% and 11.4%, respectively. Abnormal levels of TC, TG, VLDL, LDL-C and HDL-C were observed for 55.4%, 31.4%, 29.2%, 47.5% and 21.8% of participants, respectively. Adjusting for potential confounders, cigarette smoking was positively associated with higher odds of TG and VLDL (OR=4.27; 95% CI 1.69 to 10.77; and 3.26; 95% CI 1.33 to 8.03, respectively) with a significant dose-response relationship (p value for trend=0.010 and 0.030, respectively). Alcohol drinking and high saturated fat intake (≥10% energy intake) were associated with higher odds of LDL-C (OR=1.68; 95% CI 1.01 to 2.82 and OR= 1.73; 95% CI 1.02 to 2.93). Physical activity did not associate significantly with any blood lipid parameter. The demonstrated positive associations between smoking, alcohol drinking and high saturated fat intake with adverse lipoprotein levels lay further evidence for clinical practitioners, public health professionals and dietitians in the development of preventive strategies among subjects with a high risk of cardiovascular diseases in Lebanon and other neighbouring countries with similar epidemiological profile.

Prevalence and associations of behavioural risk factors with blood lipids profile in Lebanese adults: findings from WHO STEPwise NCD cross-sectional survey.

BMJ open

medicine

To examine the impact of critical care on future alcohol-related behaviour. Further, it aimed to explore patterns of recovery for patients with and without alcohol use disorders beyond the hospital environment. In-depth, semistructured interviews with participants (patients) 3-7 months post intensive care discharge. The setting for this study was a 20-bedded mixed intensive care unit (ICU), in a large teaching hospital in Scotland. On admission, patients were allocated to one of the three alcohol groups: low risk, harmful/hazardous and alcohol dependency. 21 participants who received mechanical ventilation for greater than 3 days were interviewed between March 2013 and June 2014. None. Four themes which impacted on recovery from ICU were identified in this patient group: psychological resilience, support for activities of daily living, social support and cohesion and the impact of alcohol use disorders on recovery. Participants also discussed the importance of personalised goal setting and appropriate and timely rehabilitation for alcohol-related behaviours during the critical care recovery period. There is a significant interplay between alcohol misuse and recovery from critical illness. This study has demonstrated that at present, there is a haphazard approach to rehabilitation for patients after ICU. A more targeted rehabilitation pathway for patients leaving critical care, with specific emphasis on alcohol misuse if appropriate, requires to be generated.

Health and social consequences of an alcohol-related admission to critical care: a qualitative study.

BMJ open

medicine

Slavery and human trafficking are crimes involving the violation of human rights and refer to exploitative situations where an individual cannot refuse or leave due to threats, coercion or abuse of power. Activities involving slavery include forced labour exploitation, forced sexual exploitation, forced marriage and servitude. Epidemiological studies show high levels of mental health need and poor provision of appropriate support for survivors. What mental health recovery means to victims/survivors and how it could be promoted is under-researched. A grounded theory study based on individual interviews will be undertaken. Survivors across the UK will be identified and recruited from non-governmental organisations and via social media. As per grounded theory methodology, data collection and analysis will be undertaken concurrently and recruitment will continue until theoretical saturation is reached. It is anticipated that approximately 30 participants will be recruited. Interviews will be audio recorded, transcribed verbatim and uploaded to NVivo V.11. The constant comparative method will be used to analyse the data, in order to produce a theoretical framework for mental health recovery that is grounded in the experiences of survivors. Ethical approval has been obtained from the Faculty of Medicine and Health Sciences Ethics Committee at the University of Nottingham. The findings of the study will be disseminated to academic, professional and survivor-based audiences to inform future policy developments and the provision of mental health recovery support to this population.

Mental health recovery for survivors of modern slavery: grounded theory study protocol.

BMJ open

medicine

Child (infant and under-5) and maternal mortality rates are key indicators for assessing the health status of populations. South Africa's maternal and child mortality rates are high, and the country mirrors the continental trend of slow progress towards its Millennium Development Goals. Rural areas are often more affected regarding child and maternal mortalities, specifically in areas with a high HIV burden. This study aims to understand the factors affecting child and maternal mortality in the Africa Centre Demographic Surveillance Area (DSA) from 2003 to 2014 towards developing tailored interventions to reduce the deaths in resource poor settings. This will be done by identifying child and maternal mortality 'hotspots' and their associated risk factors. This retrospective study will use data for 2003-2014 from the Africa Centre Demographic Information System (ACDIS) in rural KwaZulu-Natal Province, South Africa. All homesteads in the study area have been mapped to an accuracy of <2 m, all deaths recorded and the assigned cause of death established using a verbal autopsy interview. Advanced spatial-temporal clustering techniques (both regular (Kulldorff) and irregular (FleXScan)) will be used to identify mortality 'hotspots'. Various advanced statistical modelling approaches will be tested and used to identify significant risk factors for child and maternal mortality. Differences in attributability and risk factors profiles in identified 'hotspots' will be assessed to enable tailored intervention guidance/development. This multicomponent study will enable a refined intervention model to be developed for typical rural populations with a high HIV burden. Ethical approval was received from the Biomedical Research Ethics Committee (BREC) of the University of KwaZulu-Natal (BE 169/15).

Spatial-temporal dynamics and structural determinants of child and maternal mortality in a rural, high HIV burdened South African population, 2000-2014: a study protocol.

BMJ open

medicine

Very-low birthweight (VLBW, <1500 g) infants comprise about 1%-1.4% of all births in high-income countries. Every year, about 3000 VLBW babies in Australia and New Zealand receive intensive care. Many die or else survive with severe brain injury, retinopathy, late-onset sepsis or necrotising enterocolitis (NEC), each of which carries substantial risk of disability. This trial tests whether adding bovine lactoferrin (bLF) to feeds in VLBW infants improves (1) survival to hospital discharge free from brain injury, late-onset sepsis, NEC and treated retinopathy of prematurity (primary composite end point); (2) each component of the primary composite end point and (3) time to reach full enteral feeds, number of blood transfusions, chronic lung disease and length of hospital stay. It includes a cost-effectiveness analysis of bLF in improving survival free from major morbidity, and evaluates the effect of bLF on survival and developmental outcomes at 24 to 36 months corrected gestational age.This is a multicentre, two-arm, randomised trial comparing the treatment group receiving bLF added to breast milk or formula milk daily (up to 250 mg/kg/day bLF) versus the control group receiving no bLF supplementation. The intervention is administered until 34 completed weeks corrected gestation or for 2 weeks, whichever is longer, or until discharge home, if earlier. The target sample size of 1500 participants yields 85% power, at the two-sided 5% level significance, to detect a difference in proportions meeting the primary outcome assuming the true probability is 74% in controls and 80.5% in the bLF group. This protocol was approved by Northern Sydney Local Human Research Ethics Committee in January 2017 (Version 2.0, Reference 1003-118M) and other relevant ethics committees. The findings of the trial will be disseminated through peer-reviewed journals and conference presentations. ACTRN12611000247976; Pre-results.

Protocol for the Lactoferrin Infant Feeding Trial (LIFT): a randomised trial of adding lactoferrin to the feeds of very-low birthweight babies prior to hospital discharge.

BMJ open

medicine