bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular characterisation of Mycobacterium bovis isolated from African buffaloes (Syncerus caffer) in Hluhluwe-iMfolozi Park in KwaZulu-Natal, South Africa
Authors: Hlokwe Tiny M. , Jenkins Akinbowale O. , Streicher Elizabeth M. , Venter Estelle H. , Cooper Dave , Godfroid Jacques , Michel Anita L.
Published: June 2011

Bovine tuberculosis (BTB), a chronic disease of mammals caused by Mycobacterium bovis, is a threat to South African wildlife. It has been reported that African buffaloes (Syncerus caffer) are reservoir hosts of BTB in South African wildlife populations. This study reports on the molecular identification and typing of 31 M. bovis isolates collected between 1993 and 2008, mainly from buffaloes but also from two lions and a bush pig, in the Hluhluwe-iMfolozi Park (HiP) in KwaZulu-Natal. To study the dynamics of BTB in the buffalo populations, 28 M. bovis isolates from the HiP and epidemiologically related parks were characterised using regions of difference deletion analysis for species identification and spoligotyping, variable number of tandem repeats (VNTR), polymorphic G–C-rich sequences and IS6110 restriction fragment length polymorphism (RFLP) genotyping methods. At least three distinct M. bovis genotypes were found amongst HiP samples. The combination of VNTR typing (using a 16-loci panel) and IS6110 RFLP revealed the presence of three additional genetic profiles in individual buffaloes, demonstrating that the highest level of discrimination was achieved by these typing methods. One of the observed spoligotypes (SB0130) was dominant and represented 75% of isolates from buffaloes. A novel M. bovis spoligotype (SB1474), which is reported for the first time in this study, was observed in 14.3% of isolates from buffaloes. Based on the observed genetic relationships, the findings suggest independent introductions from at least three unrelated sources. These findings improve the knowledge regarding the diversity of circulating M. bovis strains in the HiP.
Responding to L2 Students in College Writing Classes: Teacher Perspectives
Authors: FERRIS DANA , BROWN JEFFREY , LIU HSIANG (SEAN) , STINE MARIA EUGENIA ARNAUDO
Published: June 2011

Response to student writing has been a research concern for composition specialists for the past several decades. However, most research to date has utilized student opinions or researcher judgments about teacher feedback, with researchers rarely consulting teachers themselves as informants. Also, first language (L1) and second language (L2) response research has been completed and disseminated in separate arenas, with little consideration given to the current blurring of boundaries in many educational contexts between L1 and L2 student writers. In the study described in this article, college writing instructors in both mainstream and specialized L2 writing contexts were surveyed (N= 129) and interviewed (N= 23) about their backgrounds (training and experience) and their philosophies and practices with regard to response. In addition, samples of their commentary on student papers (3–5 papers per interview subject) were collected, discussed with the instructors, and analyzed. Although most instructors were aware of adapting their approach to feedback for L2 writers, the nature of these adjustments varied dramatically across subjects, as did their overall attitude toward the endeavor of responding to L2 writers. The article concludes with a discussion of practical implications of the findings for teacher response practices and for professional preparation of L1 writing instructors who work with L2 students.
Investigation of nucleation events vertical extent: a long term study at two different altitude sites
Authors: Boulon J. , Sellegri K. , Hervo M. , Picard D. , Pichon J.-M. , Fréville P. , Laj P.
Published: June 2011

Abstract. In this work we present an analysis of the occurrence of nucleation events during more than three years of measurements at two different rural altitude sites, the puy de Dôme research station (1465 m a.s.l.) and the Opme station (660 m a.s.l.), central France. The collected database is a unique combination of scanning mobility particle sizer (10–400 nm), air ion spectrometers (from 0.8 to 42 nm for NTP-conditions), and, neutral clusters and air ion spectrometers (from 0.8 to 42 nm for NTP-conditions) measurements at these two different altitudes nearly located research stations, from February 2007 to June 2010. The seasonality of the frequency of nucleation events was studied at the puy de Dôme station and maximum of events frequency was found during early spring and early autumn. During the measurement period, neither the particle formation rates (J2= 1.382 ± 0.195 s−1) nor the growth rates (GR1.3−20 nm = 6.20 ± 0.12 nm h−1) differ from one site to the other on average. Hovewer, we found that, on 437 sampling days in common to the two sites, the nucleation frequency was higher at the puy de Dôme station (35.9 %, 157 days) than at the low elevation station of Opme (20.8 %, 91 days). LIDAR measurements and the evolution of the potential equivalent temperature revealed that the nucleation could be triggered either (i) within the whole low tropospheric column at the same time from the planetary boundary layer to the top of the interface layer (29.2 %, 47 events), (ii) above the planetary boundary layer upper limit (43.5 %, 70 events), and (iii) at low altitude and then transported, conserving dynamic and properties, at high altitude (24.8 %, 40 events). This is the first time that the vertical extent of nucleation can be studied over a long observational period, allowing for a rigorous statistical analysis of the occurrence of nucleation over the whole lower troposphere. This work highlights the fact that nucleation can occur over a large vertical extent, at least the whole low tropospheric column, and also the fact that it occurs twice as frequently as actually detected in the planetary boundary layer. The role of sulfuric acid and ions in the nucleation process was investigated at the altitude station and no correlation was found between nucleation events and the estimated sulfuric acid concentrations. However, the contribution of ion-induced nucleation was found to be relatively high (12.49 ± 2.03 % of the total nucleation rate).
Better constraints on sources of carbonaceous aerosols using a combined 14C – macro tracer analysis in a European rural background site
Authors: Gilardoni S. , Vignati E. , Cavalli F. , Putaud J. P. , Larsen B. R. , Karl M. , Stenström K. , Genberg J. , Henne S. , Dentener F.
Published: June 2011

Abstract. The source contributions to carbonaceous PM2.5 aerosol were investigated at a European background site at the edge of the Po Valley, in Northern Italy, during the period January–December 2007. Carbonaceous aerosol was described as the sum of 8 source components: primary (1) and secondary (2) biomass burning organic carbon, biomass burning elemental carbon (3), primary (4) and secondary (5) fossil organic carbon, fossil fuel burning elemental carbon (6), primary (7) and secondary (8) biogenic organic carbon. The mass concentration of each component was quantified using a set of macro tracers (organic carbon OC, elemental carbon EC, and levoglucosan), micro tracers (arabitol and mannitol), and 14C measurements. This was the first time that 14C measurements covered a full annual cycle with daily resolution. This set of 6 tracers, together with assumed uncertainty ranges of the ratios of OC-to-EC, and the reference fraction of modern carbon in the 8 source categories, provides strong constraints to the source contributions to carbonaceous aerosol. The uncertainty of contributions was assessed with a Quasi-Monte Carlo (QMC) method accounting for the variability of OC and EC emission factors, the uncertainty of reference fractions of modern carbon, and the measurement uncertainty. During winter, biomass burning composed 64 % (±15 %) of the total carbon (TC) concentration, while in summer secondary biogenic OC accounted for 50 % (±16 %) of TC. The contribution of primary biogenic aerosol particles was negligible during the entire year. Moreover, aerosol associated with fossil sources represented 27 % (±16 %) and 41 % (±26 %) of TC in winter and summer, respectively. The contribution of secondary organic aerosol (SOA) to the organic mass (OM) was significant during the entire year. SOA accounted for 30 % (±16 %) and 85 % (±12 %) of OM during winter and summer, respectively. While the summer SOA was dominated by biogenic sources, winter SOA was mainly due to biomass burning and fossil sources. This indicates that the oxidation of semi-volatile and intermediate volatility organic compounds co-emitted with primary organics is a significant source of SOA, as suggested by recent model results and Aerosol Mass Spectrometer measurements. Comparison with previous global model simulations, indicates a strong underestimate of wintertime primary aerosol emissions in this region. The comparison of source apportionment results in different urban and rural areas showed that the sampling site was mainly affected by local aerosol sources during winter and regional air masses from the nearby Po Valley in summer. This observation was further confirmed by back-trajectory analysis applying the Potential Source Contribution Function method to identify potential source regions.
Chemical characteristics of inorganic ammonium salts in PM2.5 in the atmosphere of Beijing (China)
Authors: Ianniello A. , Spataro F. , Esposito G. , Allegrini I. , Hu M. , Zhu T.
Published: June 2011

Abstract. The atmospheric concentrations of gaseous HNO3, HCl and NH3 and their relative salts have been measured during two field campaigns in the winter and in the summer of 2007 at Beijing (China), as part of CAREBEIJING (Campaigns of Air Quality Research in Beijing and Surrounding Region). In this study, annular denuder technique was used with integration times of 2 and 24 h to collect inorganic and soluble PM2.5 without interferences from gas-particle and particle-particle interactions. The results were discussed from the standpoint of temporal and diurnal variations and meteorological effects. Fine particulate Cl−, NH4+ and SO42− exhibited distinct temporal variations, while fine particulate NO3− did not show much variation with respect to season. Daily mean concentrations of fine particulate NH4+ and SO42− were higher during summer (12.30 μg m−3 and 18.24 μg m−3, respectively) than during winter (6.51 μg m−3 and 7.50 μg m−3, respectively). Instead, daily mean concentrations of fine particulate Cl− were higher during winter (2.94 μg m−3) than during summer (0.79 μg m−3), while fine particulate NO3− showed similar variations both in winter (8.38 μg m−3) and in summer (9.62 μg m−3) periods. However, the presence of large amounts of fine particulate NO3− even in summer are due to higher local and regional concentrations of NH3 in the atmosphere available to neutralize H2SO4 and HNO3, which is consistent with the observation that the measured particulate species were neutralized. Indeed, the composition of fine particulate matter indicated the domination of (NH4)2SO4 during winter and summer periods. In addition, the high relative humidity conditions in summer period seemed to dissolve a significant fraction of HNO3 and NH3 enhancing fine particulate NO3− and NH4+ in the atmosphere. All measured particulate species showed diurnal similar patterns during the winter and summer periods with higher peaks in the early morning, especially in summer, when humid and stable atmospheric conditions occurred. These diurnal variations were affected nearly by wind direction suggesting regional and local source influences. Indeed, the fine particulate species were also correlated with NOx and PM2.5, supporting the hypothesis that the traffic may be also an important source of secondary particles.
Chronic Pruritus
Authors: Butler Daniel C. , Berger Timothy , Elmariah Sarina , Kim Brian , Chisolm Sarah , Kwatra Shawn G. , Mollanazar Nicholas , Yosipovitch Gil
Published: May 2024

Importance

Chronic pruritus, defined as itch experienced for 6 weeks or longer, affects approximately 22% of people in their lifetime. Approximately 1% of physician visits are for the chief concern of chronic pruritus. Chronic pruritus is associated with adverse outcomes, including impaired sleep and reduced quality of life.

Observations

Chronic pruritus can be categorized by etiology into inflammatory, neuropathic, or a combination of inflammatory and neuropathic pruritus. Chronic pruritus is due to inflammation in approximately 60% of patients and may be caused by eczema, psoriasis, or seborrheic dermatitis. Chronic pruritus is due to a neuropathic or mixed etiology in approximately 25% of patients. Neuropathic causes of chronic pruritus include postherpetic neuralgia and notalgia paresthetica and are typically due to localized or generalized nerve dysregulation. Approximately 15% of people with chronic pruritus have other causes including systemic diseases with secondary itch, such as uremic pruritus and cholestatic pruritus, medication-induced pruritus such as pruritus due to immunotherapy, and infectious etiologies such as tinea corporis and scabies. When few primary changes are present, a thorough history, review of symptoms, and laboratory evaluation should be performed, particularly for people with chronic pruritus lasting less than 1 year. Clinicians should consider the following tests: complete blood cell count, complete metabolic panel, and thyroid function testing to evaluate for hematologic malignancy, liver disease, kidney disease, or thyroid disease. First-line treatment for inflammatory chronic pruritus includes topical anti-inflammatory therapies such as hydrocortisone (2.5%), triamcinolone (0.1%), or tacrolimus ointment. Approximately 10% of patients do not respond to topical therapies. In these patients, referral to dermatology and systemic oral or injectable treatments such as dupilumab or methotrexate may be considered. When no underlying systemic disease associated with pruritus is identified, patients are likely to have neuropathic chronic pruritus or mixed etiology such as chronic pruritus of unknown origin. In these patients, neuropathic topical treatments such as menthol, pramoxine, or lidocaine can be used either alone or in combination with immunomodulatory agents such as topical steroids. Other effective therapies for neuropathic pruritus include gabapentin, antidepressants such as sertraline or doxepin, or opioid receptor agonist/antagonists such as naltrexone or butorphanol.

Conclusions and Relevance

Chronic pruritus can adversely affect quality of life and can be categorized into inflammatory, neuropathic, or a combined etiology. First-line therapies are topical steroids for inflammatory causes, such as hydrocortisone (2.5%) or triamcinolone (0.1%); topical neuropathic agents for neuropathic causes, such as menthol or pramoxine; and combinations of these therapies for mixed etiologies of chronic pruritus.
Accounting for Competing Risks in Clinical Research
Authors: Austin Peter C. , Ibrahim Maria , Putter Hein
Published: May 2024

This JAMA Guide to Statistics and Methods article discusses accounting for competing risks in clinical research.
Ransomware Attacks, ED Visits and Inpatient Admissions in Targeted and Nearby Hospitals
Authors: Abouk Rahi , Powell David
Published: May 2024

This case-control study analyzes disruptive ransomware attacks against hospitals in California from 2014 to 2020 and emergency department (ED) and inpatient admissions in attacked and nearby hospitals.
Chitosan‐Decorated Alumina Hybrid Nanoparticles as Smart Scavengers of HF and Dissolved Transition Metals in Lithium‐Ion Batteries
Authors: Callegari Daniele , Canini Mattia , Davino Stefania , Coduri Mauro , Mustarelli Piercarlo , Quartarone Eliana
Published: May 2024

Lithium‐ion cells encompassing LiPF6 as the lithium salt and high‐voltage (LiNi0.5Mn1.5O4, LNMO) or high‐capacity (LiNi0.8Mn0.1Co0.1O2, NMC811) cathode materials are prone to transition metal (TM) dissolution caused by HF, whose formation is catalyzed by H2O traces. TM ions can shuttle to the anodic compartment, increasing the cell degradation rate. Accordingly, specific self‐healing strategies are helpful to develop scavengers able to eliminate HF and absorb TM ions so avoiding their shuttling. In this work, the fabrication and test of a bi‐functional, autonomous scavenging agent made of Al2O3 particles decorated is reported with chitosan. The nanometric Al2O3 core is a trap for HF by chemical bonding. The chitosan coating is acid‐sensitive, and the opening of such a capping layer is triggered in the presence of even small amounts of HF, leading to an efficient TM ion‐trapping. In addition, chitosan is biocompatible, biodegradable, and abundant, which is relevant for design‐for‐recycling scopes. With ≈200 ppm of water in the electrolyte, 12 wt% of scavenger causes, after 200 cycles at 1C, an increase of capacity retention from 73% to 88% for LNMO, and, impressively, from 46% to 84% for NMC811. This autonomous self‐healing mechanism is promising for application in next‐generation smart cells without requiring any external sensing.
Targeting TUBB3 Suppresses Anoikis Resistance and Bone Metastasis in Prostate Cancer
Authors: Dong Bingqi , Gu Yanlun , Sun Xiaojiao , Wang Xin , Zhou Ying , Rong Zhuona , Zhang Jixin , Shi Xuedong , Zhang Zhuo , He Xu , Chen Lin , Xiong Qingqing , Pang Xiaocong , Cui Yimin
Published: May 2024

Bone metastases occur in more than 70% of advanced prostate cancer (PCa) patients, leading to a poor prognosis. Resistance to detachment‐induced apoptosis, also known as anoikis, plays a crucial role in the onset of tumor metastasis. Targeting anoikis resistance is of immense therapeutic significance in repression of metastatic spread. In this study, based on an anoikis‐related prognostic risk model of PCa, this study identifies TUBB3 as a key anoikis‐related prognostic gene that is highly expressed in bone metastatic PCa. TUBB3 expression is increased in anoikis‐resistant PCa cells, and TUBB3 depletion significantly reverses anoikis resistance during extracellular matrix (ECM) detachment and inhibits anoikis‐resistance‐induced PCa cell invasion and migration as well as epithelial‐mesenchymal transition (EMT) process. TUBB3 knockdown significantly reduces αvβ3/FAK/Src axis activation, blocking its downstream oncogenic signaling. In addition, this work develops bone‐targeting lipid nanoparticles (BT‐LNP) based on bisphosphonate‐modified ionizable lipid for systemic delivery of siRNA targeting TUBB3 (siTUBB3). BT‐LNP‐delivered siTUBB3 therapy with localization in the bone microenvironment significantly attenuate PCa bone metastasis progression in vivo upon intravenous administration. These findings pinpoint that TUBB3, as a key regulator of anoikis resistance, is an effective therapeutic target in bone metastatic PCa and that BT‐LNP‐mediated systemic delivery of siTUBB3 can be developed as a novel therapeutic strategy for this disease.
5‐Hydroxymethylfurfural and its Downstream Chemicals: A Review of Catalytic Routes
Authors: Chen Chunlin , Lv Mingxin , Hu Hualei , Huai Liyuan , Zhu Bin , Fan Shilin , Wang Qiuge , Zhang Jian
Published: May 2024

Biomass assumes an increasingly vital role in the realm of renewable energy and sustainable development due to its abundant availability, renewability, and minimal environmental impact. Within this context, 5‐hydroxymethylfurfural (HMF), derived from sugar dehydration, stands out as a critical bio‐derived product. It serves as a pivotal multifunctional platform compound, integral in synthesizing various vital chemicals, including furan‐based polymers, fine chemicals, and biofuels. The high reactivity of HMF, attributed to its highly active aldehyde, hydroxyl, and furan ring, underscores the challenge of selectively regulating its conversion to obtain the desired products. This review highlights the research progress on efficient catalytic systems for HMF synthesis, oxidation, reduction, and etherification. Additionally, it outlines the techno‐economic analysis (TEA) and prospective research directions for the production of furan‐based chemicals. Despite significant progress in catalysis research, and certain process routes demonstrating substantial economics, with key indicators surpassing petroleum‐based products, a gap persists between fundamental research and large‐scale industrialization. This is due to the lack of comprehensive engineering research on bio‐based chemicals, making the commercialization process a distant goal. These findings provide valuable insights for further development of this field.
Unzippable Siamese Nanoparticles for Programmed Two‐Stage Cancer Immunotherapy
Authors: Long Mei , Zhou Yanfeng , Guo Daoxia , Zhu Qingyun , Liang Huan , Ji Xiaoyuan , Chen Nan , Song Haiyun
Published: May 2024

Epigenetic drugs (epi‐drugs) can destruct cancer cells and initiate both innate and adaptive immunity, yet they have achieved very limited success in solid tumors so far, partly attributing to their concurrent induction of the myeloid‐derived suppressor cell (MDSC) population. Here, dissociable Siamese nanoparticles (SIANPs) are developed for tumor cell‐targeted delivery of epi‐drug CM‐272 and MDSC‐targeted delivery of small molecule inhibitor Ibrutinib. The SIANPs are assembled via interparticle DNA annealing and detached via tumor microenvironment‐triggered strand separation. Such binary regulation induces endogenous retrovirus expression and immunogenic cell death in tumor cells while restraining the immunosuppressive effects of MDSCs, and synergistically promotes dendritic cell maturation and CD8+ T cell activation for tumor inhibition. Significantly, immune microenvironment remodeling via SIANPs further overcomes tumor resistance to immune checkpoint blockade therapy. This study represents a two‐pronged approach for orchestrating immune responses, and paves a new way for employing epi‐drugs in cancer immunotherapy.
Hybrid Surface Modification and Bulk Doping Enable Spent LiCoO2 Cathodes for High‐Voltage Operation
Authors: Liu Zhenzhen , Han Miaomiao , Zhang Shengbo , Li Huaimeng , Wu Xi , Fu Zhen , Zhang Haimin , Wang Guozhong , Zhang Yunxia
Published: May 2024

The emerging market demand for high‐energy‐density of energy storage devices is pushing the disposal of end‐of‐life LiCoO2 (LCO) to shift toward sustainable upgrading into structurally stable high‐voltage cathode materials. Herein, an integrated bulk and surface commodification strategy is proposed to render spent LCO (S‐LCO) to operate at high voltages, involving bulk Mn doping, near surface P gradient doping, and Li3PO4/CoP (LPO/CP) coating on the LCO surface to yield upcycled LCO (defined as MP‐LCO@LPO/CP). Benefiting from hybrid surface coating with Li+‐conductive Li3PO4 (LPO) and electron conductive CoP (CP) coupled with Mn and P co‐doping, the optimized MP‐LCO@LPO/CP cathode exhibits enhanced high‐voltage performance, delivering an initial discharge capacity of 218.8 mAh g−1 at 0.2 C with excellent capacity retention of 80.9% (0.5 C) after 200 cycles at a cut‐off voltage of 4.6 V, along with 96.3% of capacity retention over 100 cycles at 4.5 V. These findings may afford meaningful construction for the upcycling of commercial S‐LCO into next‐generation upmarket cathode materials through the elaborate surface and bulk modification design.
Imidazolidine‐Pyrroloimidazolone Pyridine‐Ni(acac)2 Complex Catalyzed Asymmetric Darzens Reaction of Isatins with Phenacyl Chlorides: A Chiral Amplification Effect
Authors: Wang Han‐Le , Wei Tao , Bi Ru‐Yun , Xie Ming‐Sheng , Guo Hai‐Ming
Published: May 2024

With phenacyl chlorides as simple nucleophilic species, the asymmetric Darzens reaction of isatins using Ni(acac)2 as the Lewis acid and imidazolidine‐pyrroloimidazolone pyridine as the ligand is reported. In the presence of 1 mol% of the catalyst, diverse spiro‐epoxyoxindoles with two new contiguous stereocenters were afforded in 82–99% yields, >20:1 dr, with 91–99% ee. Chiral spiro‐epoxyoxindoles could undergo ring‐opening reactions in further transformations. The developed method was applied to the derivatization of complex molecules including indomethacin, gemfibrozil, and febuxostat‐derived α‐chloroketones. A strong positive nonlinear effect was observed, which was caused by the precipitation of a less‐soluble racemic catalyst complex.
Asymmetric CapMix Device Exploiting Functionalized Graphene Oxide and SPEEK Coatings for Improved Energy Harvesting From Salinity Gradients
Authors: Pedico Alessandro , Molino Davide , Zaccagnini Pietro , Bocchini Sergio , Bertana Valentina , Lamberti Andrea
Published: May 2024

This work investigated the possibility of using functionalized graphene oxide and sulfonated poly(ether ether ketone) coatings on activated carbons to obtain an asymmetric device suitable for Capacitive Mixing (CapMix) application. Herein the synthesis and fabrication procedures of both materials and electrodes are reported, together with a comprehensive list of electrochemical characterization techniques. The results from the electrochemical characterization are used to design the optimal operational parameters for CapMix experiments involving the materials being studied. A homemade cell is designed and fabricated for CapMix application by polymer micromachining. Electrochemical tests are conducted to optimize the process parameters and the results of this optimization are reported, proving that both the materials and the process parameters play a key role in CapMix. The final device can generate a net power output of 12 mW m−2 by mixing simulated seawater and freshwater. This result paved the way for further application of graphene oxide in the field of renewable energy.
Circumscribing Laser Cuts Attenuate Seizure Propagation in a Mouse Model of Focal Epilepsy
Authors: Lieberman Seth , Rivera Daniel A. , Morton Ryan , Hingorani Amrit , Southard Teresa L. , Johnson Lynn , Reukauf Jennifer , Radwanski Ryan E. , Zhao Mingrui , Nishimura Nozomi , Bracko Oliver , Schwartz Theodore H. , Schaffer Chris B.
Published: May 2024

In partial onset epilepsy, seizures arise focally in the brain and often propagate. Patients frequently become refractory to medical management, leaving neurosurgery, which can cause neurologic deficits, as a primary treatment. In the cortex, focal seizures spread through horizontal connections in layers II/III, suggesting that severing these connections can block seizures while preserving function. Focal neocortical epilepsy is induced in mice, sub‐surface cuts are created surrounding the seizure focus using tightly‐focused femtosecond laser pulses, and electrophysiological recordings are acquired at multiple locations for 3–12 months. Cuts reduced seizure frequency in most animals by 87%, and only 5% of remaining seizures propagated to the distant electrodes, compared to 80% in control animals. These cuts produced a modest decrease in cortical blood flow that recovered and left a ≈20‐µm wide scar with minimal collateral damage. When placed over the motor cortex, cuts do not cause notable deficits in a skilled reaching task, suggesting they hold promise as a novel neurosurgical approach for intractable focal cortical epilepsy.
Kidney Organoid Modeling of WT1 Mutations Reveals Key Regulatory Paths Underlying Podocyte Development
Authors: Wang Gang , Wu Hangdi , Zhai Xiuwen , Zhang Li , Zhang Changming , Cheng Chen , Xu Xiaodong , Gao Erzhi , Xiong Xushen , Zhang Jin , Liu Zhihong
Published: May 2024

Wilms tumor‐1(WT1) is a crucial transcription factor that regulates podocyte development. However, the epigenomic mechanism underlying the function of WT1 during podocyte development has yet to be fully elucidated. Here, single‐cell chromatin accessibility and gene expression maps of foetal kidneys and kidney organoids are generated. Functional implications of WT1‐targeted genes, which are crucial for the development of podocytes and the maintenance of their structure, including BMPER/PAX2/MAGI2 that regulates WNT signaling pathway, MYH9 that maintains actin filament organization and NPHS1 that modulates cell junction assembly are identified. To further illustrate the functional importance of WT1‐mediated transcriptional regulation during podocyte development, cultured and implanted patient‐derived kidney organoids derived from the Induced Pluripotent Stem Cell (iPSCs) of a patient with a heterozygous missense mutation in WT1 are generated. Results from single‐cell RNA sequencing (scRNA‐seq) and functional assays confirm that the WT1 mutation leads to delays in podocyte development and causes damage to cell structures, due to its failure to activate the targeting genes MAGI2, MYH9, and NPHS1. Notably, correcting the mutation in the patient iPSCs using CRISPR‐Cas9 gene editing rescues the podocyte phenotype. Collectively, this work elucidates the WT1‐related epigenomic landscape with respect to human podocyte development and identifies the disease‐causing role of a WT1 mutation.
Machine‐Learning‐Assisted Discovery of Mechanosynthesized Lead‐Free Metal Halide Perovskites for the Oxidative Photocatalytic Cleavage of Alkenes
Authors: Xiao Yonghao , Choudhuri Khokan , Thanetchaiyakup Adisak , Chan Wei Xin , Hu Xinwen , Sadek Mansour , Tam Ying Hern , Loh Ryan Guanying , Shaik Mohammed Sharifah Nadhirah Binte , Lim Kendric Jian Ying , Ten Ju Zheng , Garcia Felipe , Chellappan Vijila , Choksi Tej S. , Lim Yee‐Fun , Soo Han Sen
Published: May 2024

Lead‐free metal halide perovskites can potentially be air‐ and water‐stable photocatalysts for organic synthesis, but there are limited studies on them for this application. Separately, machine learning (ML), a critical subfield of artificial intelligence, has played a pivotal role in identifying correlations and formulating predictions based on extensive datasets. Herein, an iterative workflow by incorporating high‐throughput experimental data with ML to discover new lead‐free metal halide perovskite photocatalysts for the aerobic oxidation of styrene is described. Through six rounds of ML optimization guided by SHapley Additive exPlanations (SHAP) analysis, BA2CsAg0.95Na0.05BiBr7 as a photocatalyst that afforded an 80% yield of benzoic acid under the standard conditions is identified, which is a 13‐fold improvement compared to the 6% with when using Cs2AgBiBr6 as the initial photocatalyst benchmark that is started. BA2CsAg0.95Na0.05BiBr7 can tolerate various functional groups with 22 styrene derivatives, highlighting the generality of the photocatalytic properties demonstrated. Radical scavenging studies and density functional theory calculations revealed that the formation of the reactive oxygen species superoxide and singlet oxygen in the presence of BA2CsAg0.95Na0.05BiBr7 are critical for photocatalysis.
Peptide Boronic Acids by Late‐Stage Hydroboration on the Solid Phase
Authors: Werner Marius , Brinkhofer Julian , Hammermüller Leon , Heim Thomas , Pham Truc Lam , Huber Jonas , Klein Christian , Thomas Franziska
Published: May 2024

Organoboron compounds have a wide range of applications in numerous research fields, and methods to incorporate them in biomolecules are much sought after. Here, on‐resin chemical syntheses of aliphatic and vinylogous peptide boronic acids are presented by transition metal‐catalyzed late‐stage hydroboration of alkene and alkyne groups in peptides and peptoids, for example on allyl‐ and propargylglycine residues, using readily available chemicals. These methods yield peptide boronic acids with much shorter linkers than previously reported on‐resin methods. Furthermore, the methods are regio‐ and stereoselective, compatible with all canonical amino acid residues and can be applied to short, long, and in part even “difficult” peptide sequences. In a feasibility study, the protected peptide vinylboronic acids are further derivatized by the Petasis reaction using salicylaldehyde derivatives. The ability of the obtained peptide boronic acids to reversibly bind to carbohydrates is demonstrated in a catch‐release model experiment using a fluorescently labeled peptide boronic acid on cross‐linked dextran beads. In summary, this highlights the potential of the target compounds for drug discovery, glycan‐specific target recognition, controlled release, and diagnostics.
Engineering Efferocytosis‐Mimicking Nanovesicles to Regulate Joint Anti‐Inflammation and Peripheral Immunosuppression for Rheumatoid Arthritis Therapy
Authors: Yuan Shanshan , Chai Yingqian , Xu Jianghua , Wang Youchao , Jiang Lihua , Lu Ning , Jiang Hongyi , Wang Jilong , Pan Xiaoyun , Deng Junjie
Published: May 2024

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic inflammation of the synovial joints and the dysfunction of regulatory T cells (Tregs) in the peripheral blood. Therefore, an optimal treatment strategy should aim to eliminate the inflammatory response in the joints and simultaneously restore the immune tolerance of Tregs in peripheral blood. Accordingly, we developed an efferocytosis‐mimicking nanovesicle that contains three functional factors for immunomodulating of efferocytosis, including “find me” and “eat me” signals for professional (macrophage) or non‐professional phagocytes (T lymphocyte), and “apoptotic metabolite” for metabolite digestion. We showed that efferocytosis‐mimicking nanovesicles targeted the inflamed joints and spleen of mice with collagen‐induced arthritis, further recruiting and selectively binding to macrophages and T lymphocytes to induce M2 macrophage polarization and Treg differentiation and T helper cell 17 (Th17) recession. Under systemic administration, the efferocytosis‐mimicking nanovesicles effectively maintained the pro‐inflammatory M1/anti‐inflammatory M2 macrophage balance in joints and the Treg/Th17 imbalance in peripheral blood to prevent RA progression. This study demonstrates the potential of efferocytosis‐mimicking nanovesicles for RA immunotherapy.
Hemiarhinia caused by a missense variation in SMCHD1: A mild phenotype in the clinical spectrum of Bosma arhinia microphthalmia syndrome
Authors: Kokitsu‐Nakata Nancy Mizue , Segarra Vinicius Contrucci Dantas , Tonello Cristiano , Brandão Michele Madeira , Alonso Nivaldo , Zechi‐Ceide Roseli Maria
Published: May 2024

Bosma arhinia microphthalmia syndrome (BAMS, OMIM #603457) is a rare autosomal dominant disorder caused by heterozygous variation in the SMCHD1 gene on chromosome 18p11. Clinically, it is characterized by microphthalmia, absence or hypoplasia of nose, choanal atresia, anosmia, palatal abnormalities, hypogonadotropic hypogonadism, and cryptorchidism. Here we report a Brazilian patient with a likely pathogenic variation in SMCHD1 gene (c.1418A>T; p.Glu473Val) presenting hemiarhinia associated with short stature and hypogonadotropic hypogonadism. Due to the clinical variability of BAMS, we considered that hemiarhinia, without microphthalmia, in the present case, can be considered a mild form of BAMS and could be considered for screening of SMCHD1 gene variation.
Oesophagostomum stephanostomum causing parasitic granulomas in wild chimpanzees (Pan troglodytes verus) of Taï National Park, Côte d'Ivoire
Authors: Jaffe Jenny E. , Metzger Sonja , Mätz‐Rensing Kerstin , Ribas Alexis , Wittig Roman M. , Leendertz Fabian H.
Published: May 2024

Nematodes belonging to the genus Oesophagostomum frequently infect wild chimpanzees (Pan troglodytes) across widely separated field sites. Nodular lesions (granulomas) containing Oesophagostomum are commonly seen in the abdomen of infected chimpanzees post‐mortem. At Taï National Park, Côte d'Ivoire, previous studies have identified larvae of a variety of Oesophagostomum spp. in wild chimpanzee stool, based on sequencing of larval DNA, and nodular lesions associated with Oesophagostomum, identified morphologically to the genus level but not sequenced. Here we present three recent cases of parasitic granulomas found post‐mortem in chimpanzees at Taï. We complement descriptions of gross pathology, histopathology and parasitology with PCR and sequencing of DNA isolated from the parasitic nodules and from adult worms found inside the nodules. In all three cases, we identify Oesophagostomum stephanostomum as the causative agent. The sequences from this study were identical to the only other published sequences from nodules in nonhuman primates—those from the wild chimpanzees of Gombe, Tanzania.
Merged Molecular Switches Excel as Optoacoustic Dyes: Azobenzene–Cyanines Are Loud and Photostable NIR Imaging Agents
Authors: Müller Markus , Liu Nian , Gujrati Vipul , Valavalkar Abha , Hartmann Sean , Anzenhofer Pia , Klemm Uwe , Telek András , Dietzek‐Ivanšić Benjamin , Hartschuh Achim , Ntziachristos Vasilis , Thorn‐Seshold Oliver
Published: May 2024

Optoacoustic (or photoacoustic) imaging promises micron‐resolution noninvasive bioimaging with much deeper penetration (>cm) than fluorescence. However, optoacoustic imaging of enzyme activity would require loud, photostable, NIR‐absorbing molecular contrast agents, which remain unknown. Most organic molecular contrast agents are repurposed fluorophores, with severe shortcomings of photoinstability or phototoxicity under optoacoustic imaging, as consequences of their slow S1→S0 electronic relaxation. We now report that known fluorophores can be rationally modified to reach ultrafast S1→S0 rates, without much extra molecular complexity, simply by merging them with molecular switches. Here, we merge azobenzene switches with cyanine dyes to give ultrafast relaxation (<10 ps, >100‐fold faster). Without even adapting instrument settings, these azohemicyanines display outstanding improvements in signal longevity (>1000‐fold increase of photostability) and signal loudness (>3‐fold even at time zero). We show why this simple but unexplored design strategy can still offer stronger performance in the future, and can also increase the spatial resolution and the quantitative linearity of photoacoustic response over extended longitudinal imaging. By bringing the world of molecular switches and rotors to bear on problems facing optoacoustic agents, this practical strategy will help to unleash the full potential of optoacoustic imaging in fundamental studies and translational uses.
Inhibiting Dissolution of Active Sites in 80 °C Alkaline Water Electrolysis by Oxyanion Engineering
Authors: Liu Wei , Ding Xiaoqian , Cheng Jingjin , Jing Jianlei , Li Tianshui , Huang Xin , Xie Pengpeng , Lin Xichang , Ding Hanlin , Kuang Yun , Zhou Daojin , Sun Xiaoming
Published: May 2024

Commercial alkaline water electrolysers typically operate at 80 °C to minimize energy consumption. However, NiFe‐based catalysts, considered as one of the most promising candidates for anode, encounter the bottleneck of high solubility at such temperatures. Herein, we discover that the dissolution of NiFe layered double hydroxides (NiFe‐LDH) during operation not only leads to degradation of anode itself, but also deactivates cathode for water splitting, resulting in decay of overall electrocatalytic performance. Aiming to suppress the dissolution, we employed oxyanions as inhibitors in electrolyte. The added phosphates to the electrolyte inhibit the loss of NiFe‐LDH active sites at 400 mA cm−2 to 1/3 of the original amount, thus reducing the rate of performance decay by 25‐fold. Furthermore, the usage of borates, sulfates, and carbonates yields similar results, demonstrating the reliability and universality of the active site dissolution inhibitor, and its role in elevated water electrolysis.
Structure‐Function Relationship of p‐Block Bismuth for Selective Photocatalytic CO2 Reduction
Authors: Li Jingwei , Xiang Tianci , Liu Xiang , Ghazzal Mohamed Nawfal , Liu Zhao‐Qing
Published: May 2024

Selective photocatalytic reduction of CO2 to value‐added fuels, such as CH4, is highly desirable due to its high mass‐energy density. Nevertheless, achieving selective CH4 with higher production yield on p‐block materials is hindered by non‐ideal adsorption of *CHO key intermediate and an unclear structure‐function relationship. Herein, we unlock the key reaction steps of CO2 and found a volcano‐type structure‐function relationship for photocatalytic CO2‐to‐CH4 conversion by gradual reduction of the p‐band center of the p‐block Bi element leading to formation of Bi‐oxygen vacancy heterosites. The selectivity of CH4 is also positive correlation with adsorption energy of *CHO. The Bi‐oxygen vacancy heterosites with an appropriate filled Bi‐6p orbital electrons and p band center (−0.64) enhance the coupling between C‐2p of *CHO and Bi‐6p orbitals, thereby resulting in high selectivity (95.2 %) and productivity (17.4 μmol g−1 h−1) towards CH4. Further studies indicate that the synergistic effect between Bi‐oxygen vacancy heterosites reduces Gibbs free energy for *CO‐*CHO process, activates the C−H and C=O bonds of *CHO, and facilitates the enrichment of photoexcited electrons at active sites for multielectron photocatalytic CO2‐to‐CH4 conversion. This work provides a new perspective on developing p‐block elements for selective photocatalytic CO2 conversion.
Modulating the Electrolyte Microenvironment in Electrical Double Layer for Boosting Electrocatalytic Nitrate Reduction to Ammonia
Authors: Wen Weidong , Fang Shidong , Zhou Yitong , Zhao Ying , Li Peng , Yu Xin‐Yao
Published: May 2024

Electrochemical nitrate reduction reaction (NO3RR) is a promising approach to achieve remediation of nitrate‐polluted wastewater and sustainable production of ammonia. However, it is still restricted by the low activity, selectivity and Faraday efficiency for ammonia synthesis. Herein, we propose an effective strategy to modulate the electrolyte microenvironment in electrical double layer (EDL) by mediating alkali metal cations in the electrolyte to enhance the NO3RR performance. Taking bulk Cu as a model catalyst, the experimental study reveals that the NO3−‐to‐NH3 performance in different electrolytes follows the trend Li+<Cs+<Na+<K+. Theoretical studies illustrate that the proton transport rate in NO3RR and the activity of the rate‐determining step (NO3− to NO2−) increase in the order Li+<Cs+<Na+<K+. The cation effects are also general for two typical nanostructured catalysts including copper/cuprous oxide and nickel phosphides, achieving near‐100 % Faradaic efficiency and over 99 % conversion of NO3− to NH3. Furthermore, we demonstrate that NO3− can be converted to high‐purity NH4Cl by copper/cuprous oxide catalyst in K+‐containing electrolyte.
Hypervalent Iodine Amino Acid Building Blocks for Bioorthogonal Peptide Macrocyclization
Authors: Liu Xing‐Yu , Mykhailenko Olha , Faraone Adriana , Waser Jerome
Published: May 2024

Ethynylbenziodoxol(on)es (EB(X)xs) reagents have emerged as useful reagents for peptide/protein modification due to their versatile reactivity and high selectivity. Herein, we report the successful introduction of ethynylbenziodoxoles (EBxs) on different amino acid building blocks (Lys/Orn/Dap), and show their compatibility with both solid phase peptide synthesis (SPPS) and solution phase peptide synthesis (SPS). The selective incorporation of the EBx core into peptide sequences enable efficient macrocyclizations under mild conditions for the synthesis of topologically unique cyclic and bicyclic peptides.
Variant‐Localized High‐Concentration Electrolyte without Phase Separation for Low‐Temperature Batteries
Authors: Yang Juan , Shang Jian , Liu Qirong , Yang Xinyu , Tan Yunfei , Zhao Yu , Liu Chenguang , Tang Yongbing
Published: May 2024

Dual‐ion batteries (DIBs) present great application potential in low‐temperature energy storage scenarios due to their unique dual‐ion working mechanism. However, at low temperatures, the insufficient electrochemical oxidation stability of electrolytes and depressed interfacial compatibility impair the DIB performance. Here, we design a variant‐localized high‐concentration solvation structure for universal low‐temperature electrolytes (ν‐LHCE) without the phase separation via introducing an extremely weak‐solvating solvent with low energy levels. The unique solvation structure gives the ν‐LHCE enhanced electrochemical oxidation stability. Meanwhile, the extremely weak‐solvating solvent can competitively participate in the Li+‐solvated coordination, which improves the Li+ transfer kinetics and boosts the formation of robust interphases. Thus, the ν‐LHCE electrolyte not only has a good high‐voltage stability of >5.5 V and proper Li+ transference number of 0.51 but also shows high ionic conductivities of 1 mS/cm at low temperatures. Consequently, the ν‐LHCE electrolyte enables different types of batteries to achieve excellent long‐term cycling stability and good rate capability at both room and low temperatures. Especially, the capacity retentions of the DIB are 77.7 % and 51.6 %, at −40 °C and −60 °C, respectively, indicating great potential for low‐temperature energy storage applications, such as polar exploration, emergency communication equipment, and energy storage station in cold regions.
Synthesis and in vitro cytotoxicity of benzoxazole‐based PPARα/γ antagonists in colorectal cancer cell lines
Authors: Moreno‐Rodríguez Nazaret , Laghezza Antonio , Cerchia Carmen , Sokolova Darina V. , Spirina Tatiana S. , De Filippis Barbara , Romanelli Virgilio , Recio Rocío , Fernández Inmaculada , Loiodice Fulvio , Pokrovsky Vadim S. , Ammazzalorso Alessandra , Lavecchia Antonio
Published: May 2024

A series of benzoxazole‐based amides and sulfonamides were synthesized and evaluated for their human peroxisome proliferator‐activated receptor (PPAR)α and PPARγ activity. All tested compounds showed a dual antagonist profile on both PPAR subtypes; based on transactivation results, seven compounds were selected to test their in vitro antiproliferative activity in a panel of eight cancer cell lines with different expression rates of PPARα and PPARγ. 3f was identified as the most cytotoxic compound, with higher potency in the colorectal cancer cell lines HT‐29 and HCT116. Compound 3f induced a concentration‐dependent activation of caspases and cell‐cycle arrest in both colorectal cancer models. Docking experiments were also performed to shed light on the putative binding mode of this novel class of dual PPARα/γ antagonists.
Abnormal expression of serum miR‐4746‐5p in liver cancer patients after interventional chemotherapy and its possible mechanism
Authors: Deng Keping , Wang Wei , Chi Xiaobin , Yu Yan , Zhang Yichuan , Yuan Jianming
Published: May 2024

Interventional chemotherapy is a common operation in the clinical treatment of liver cancer. The aim of this study was to investigate the expression and molecular mechanism of serum miR‐4746‐5p in liver cancer patients before and after interventional chemotherapy. The levels of miR‐4746‐5p and CDKN1C in serum samples from liver cancer patients were detected using real‐time fluorescence quantitative polymerase chain reaction. Receiver operating characteristic curves revealed the diagnostic value of miR‐4746‐5p in tumors. Differences in clinical indicators between liver cancer patients and healthy controls were assessed using Pearson correlation analysis. Luciferase reporter gene assays confirmed the targeted interaction between miR‐4746‐5p and CDKN1C. In vitro cellular assays were validated by Cell Counting Kit‐8, Transwell assay, and chemoresistance assay. Serum miR‐4746‐5p levels were increased in liver cancer patients but were downregulated after chemotherapy intervention. CDKN1C expression showed the opposite trend. Low levels of miR‐4746‐5p mediated cell growth and metastasis by targeting and negatively regulating CDKN1C expression, while silencing CDKN1C restored cell activity. Inhibition of miR‐4746‐5p reduced chemoresistance, while downregulation of CDKN1C affected cell sensitivity. miR‐4746‐5p may be a potential therapeutic factor for liver cancer diagnosis and interventional chemotherapy.