bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibody drug conjugates for the treatment of multiple myeloma
Authors: Leong Sarah , Lam Ho Pui Jeff , Kirkham Zoe , Popat Rakesh
Published: October 2022

The treatment landscape of multiple myeloma (MM) has evolved substantially, but it remains largely incurable so new treatment options are required. Antibody drug conjugates (ADCs) are an emerging therapeutic class used in Cancer to deliver targeted therapy. ADCs are composed of three components, an antibody, a chemical linker and a payload which must be chosen carefully to be effective and safe. This alternative mechanism of action to standard treatments makes ADCs an attractive class for further development. However, several ADCs have been investigated but many have not moved further than phase 1 trials, highlighting the challenges in designing an effective and tolerable ADC. Belantamab Mafodotin is currently the only ADC licensed for MM although others are currently under evaluation. Belantamab Mafodotin demonstrated efficacy as monotherapy in triple class exposed patients and combinations are under development which maintain safety with encouraging efficacy particularly at earlier lines of therapy. Retaining an acceptable adverse event profile for ADCs remains vital for their success. Strategies to mitigate ocular events for Belantamab Mafodotin involve lower and less frequent dosing as well as the use of gamma secretase inhibitors. The optimal sequencing of ADCs within the treatment pathway including novel immunotherapies is now under evaluation.
The international consensus classification of myeloid neoplasms and acute Leukemias: myeloproliferative neoplasms
Authors: Thiele Jürgen , Kvasnicka Hans Michael , Orazi Attilio , Gianelli Umberto , Gangat Naseema , Vannucchi Alessandro M. , Barbui Tiziano , Arber Daniel A. , Tefferi Ayalew
Published: October 2022

A group of international experts, including hematopathologists, oncologists, and geneticists were recently summoned (September 2021, Chicago, IL, USA) to update the 2016/17 World Health Organization classification system for hematopoietic tumors. After careful deliberation, the group introduced the new International Consensus Classification (ICC) for Myeloid Neoplasms and Acute Leukemias. This current in‐depth review focuses on the ICC‐2022 category of JAK2 mutation‐prevalent myeloproliferative neoplasms (MPNs): essential thrombocythemia, polycythemia vera, primary myelofibrosis, and MPN, unclassifiable. The ICC MPN subcommittee chose to preserve the primary role of bone marrow morphology in disease classification and diagnostics, while also acknowledging the complementary role of genetic markers for establishing clonality, facilitating MPN subtype designation, and disease prognostication.
Pd‐Catalyzed Mizoroki‐Heck Annulation and Equivalent Aminocarbonylation Reactions Enabled by Mo(CO)6‐Mediated Direct Reduction of Nitro Derivatives
Authors: Xu Shujuan , Liu Huahua , Zhu Jia , Wei Li , Chen Zhiyuan
Published: October 2022

A Pd‐catalyzed Mizoroki‐Heck annulation/equivalent aminocarbonylation reaction of alkene‐tethered aryl iodides with nitro compounds is accomplished, providing facile access to diverse carbamoyl‐substituted benzoheterocycles, such as indolin‐2‐ones and 2,3‐dihydrobenzofurans, in moderate to good yields. The cost‐effective Mo(CO)6 complex is discovered to be a solid carbonyl (CO) source and an ideal reducing agent, enabling the efficient production of the desired benzoheterocycles with broad substrate scope tolerance, including both nitroarenes and nitroalkanes under external reductant‐free conditions.
Analysis of data consistency identifies measurement abnormality in Howells' craniometric test data set
Authors: Pang Jinyong , Dong Yibo , Turner Christopher , Li Chang , Liu Xiaoming
Published: October 2022

Howells' craniometric data set is the largest publicly available craniometric data set on the internet and has been widely used in craniometric methods development. The data consists of a main data set of 2524 human crania from 28 populations and an additional “test” data set of 524 crania. Up to 82 measurements were recorded from those crania. We studied the data consistency between the main and test data sets for potential combined usage of the two. We found that the two data sets can be separated clearly via Uniform Manifold Approximation and Projection, suggesting some data inconsistency between the two. To further investigate the cause, we split the two data sets into six continental groups (African, Austro‐Melanesian, East Asian, European, Native American, and Polynesian) and tested the distribution difference between the two data sets for each of the groups. We found that the measures of simotic chord (WNB) and simotic subtense (SIS) are significantly and abnormally larger in the test data set than in the main data set. After removing the two measures, the two data sets are broadly comparable. We further showed the evidence that missing decimal points likely caused the abnormality.
A case of massive refractory diarrhea in a patient with COVID‐19
Authors: Shimizu Kentaro , Hirata Haruhiko , Tokuhira Natsuko , Ueda Akiko , Motooka Daisuke , Nakamura Shota , Ogura Hiroshi
Published: October 2022

Background

The new coronavirus disease (COVID‐19) causes gastrointestinal symptoms as well as respiratory symptoms.

Case Presentation

A 60‐year‐old man was transferred with respiratory difficulty. He was diagnosed as having COVID‐19 and was intubated and placed on mechanical ventilation. He suffered from diarrhea from day 12 and produced a maximum of approximately 6,384 mL/day of watery diarrhea on day 21. He required massive transfusion. Adsorbents and pectin‐containing oligomeric formulas were administered, which decreased the amount of diarrhea. Fecal metagenomic analysis showed the proportions of the genera Enterococcus and Staphylococcus were the most dominate at the genus level. The proportion of Bacteroidetes was <1%. Thereafter, his diarrhea decreased to several times, and he was transferred to another ward on day 104.

Conclusion

Therapy for intestinal complications as well as that for pneumonia might be important in treating COVID‐19.
An Ultraviolet Fluorophore with Narrowed Emission via Coplanar Molecular Strategy
Authors: He Xin , Lou Jingli , Li Baoxi , Wang Han , Peng Xiaoluo , Li Ganggang , Liu Lu , Huang Yu , Zheng Nan , Xing Longjiang , Huo Yanping , Yang Dezhi , Ma Dongge , Zhao Zujin , Wang Zhiming , Tang Ben Zhong
Published: October 2022

Narrowband emitting fluorophores exhibit immense potentials for organic light‐emitting diodes (OLEDs) with high color purity. However, it's still hard to simultaneously realize short‐wavelength ultraviolet (UV) or near ultraviolet emission (NUV) while maintaining a narrowed full width at half maximum (FWHM) value, and rare work focus on such challenging pursuit. Herein, an ingenious synthetic method was devised to achieve emitters with coplanar structure. 11‐(4,6‐diphenyl‐1,3,5‐triazin‐2‐yl)indolo[3,2,1‐jk]carbazole (ICZ‐TAZ) was designed to realize narrowed UV emission both in photoluminescence (PL) and electroluminescence (EL) which benefited from the suppression of vibronic coupling. UV/NUV OLEDs based on ICZ‐TAZ achieve external quantum efficiency (EQE) maximums of 3.26 % peaks @ 388 nm and 4.02 % peaks @ 406 nm with small FWHM of 32 nm and 46 nm, respectively, corresponding with reduced efficiency roll‐off at luminance of 100 cd m−2.
Synthesis of Axially Chiral CF3‐Substituted 2‐Arylpyrroles by Sequential Phosphine‐Catalyzed Asymmetric [3+2] Annulation and Oxidative Central‐to‐Axial Chirality Transfer
Authors: Xiang Alvin Tan Chuan , Li Rui , Zhang Fuhao , Dai Lei , Ullah Nisar , Lu Yixin
Published: October 2022

A sequential phosphine‐catalyzed asymmetric [3+2] annulation of aldimines with allenoates and oxidative central‐to‐axial chirality transfer strategy has been developed. This approach is operationally simple, allowing for rapid access to a range of axially chiral CF3‐containing 2‐arylpyrroles with high enantiomeric excess. Furthermore, an atroposelective synthesis of esaxerenone is presented, illustrating the practical potential of the reported method.
A Sonication‐Activated Valence‐Variable Sono‐Sensitizer/Catalyst for Autography Inhibition/Ferroptosis‐Induced Tumor Nanotherapy
Authors: Feng Wei , Liu Zhonglong , Xia Lili , Chen Meng , Dai Xinyue , Huang Hui , Dong Caihong , He Yue , Chen Yu
Published: October 2022

The effective deployment of reactive oxygen species (ROS)‐mediated oncotherapy in practice remains challenging, mired by uncontrollable catalytic processes, stern reaction conditions and safety concerns. Herein, we develop a copper nanodot integrating sonodynamic and catalytic effects within one active center, which responds to exogenous ultrasound (US) and endogenous H2O2 stimuli. US irradiation induces the valence conversion from CuII to CuI catalyzing H2O2 into ⋅OH for chemodynamic therapy. Meanwhile, valence transformation results in electron‐hole pairs separation, promoting ROS generation for sonodynamic therapy. Notably, copper nanodots not only block lysosome fusion and degradation leading to autophagy flux blockage, but also interfere with the glutathione peroxidase 4 and cystine‐glutamate antiporter SLC7A11 function achieving ferroptosis. Furthermore, reversible valence changes, inherent hydrophilicity and renal clearance ultrasmall size guarantee biosafety.
Expanded Sequence Space of Radical S‐Adenosylmethionine‐Dependent Enzymes Involved in Post‐translational Macrocyclization**
Authors: He Bei‐Bei , Cheng Zhuo , Zhong Zheng , Gao Ying , Liu Hongyan , Li Yong‐Xin
Published: October 2022

Ribosomally synthesized and post‐translationally modified peptides (RiPPs) represent one of the largest but primarily underexplored natural product families in bacteria. The genetically encoded nature of RiPPs simplifies the prediction and prioritization of their biosynthetic gene clusters (BGCs). We report a small peptide and enzyme co‐occurrence analysis workflow (SPECO), which allowed us to identify 32 220 prospective rSAM‐catalyzed RiPP BGCs from 161 954 bacterial genomes and prioritize 25 families with new biosynthetic architectures or precursor patterns. We characterized three new enzymes that respectively catalyze cysteine‐glycine (BlaB), histidine‐aliphatic side chain (ScaB), and tyrosine/histidine‐arginine (VguB) cross‐links. The cyclophane‐forming enzyme ScaB exhibits broad substrate selectivity, allowing it to catalyze diverse triceptide formation. These results demonstrate the strength of the SPECO workflow in discovering new enzymes for peptide macrocyclization.
Asymmetrically Substituted 10H,10′H‐9,9′‐Spirobi[acridine] Derivatives as Hole‐Transporting Materials for Perovskite Solar Cells
Authors: Xia Jianxing , Zhang Yi , Cavazzini Marco , Orlandi Simonetta , Ding Bin , Kanda Hiroyuki , Klipfel Nadja , Gao Xiao‐Xin , Ul Ain Qurat , Jankauskas Vygintas , Rakstys Kasparas , Hu Ruiyuan , Qiu Zeliang , Asiri Abdullah M. , Kim Hobeom , Dyson Paul J. , Pozzi Gianluca , Khaja Nazeeruddin Mohammad
Published: October 2022

Hole‐transporting materials (HTMs) based on the 10H, 10′H‐9,9′‐spirobi [acridine] core (BSA50andBSA51) were synthesized, and their electronic properties were explored. Experimental and theoretical studies show that the presence of rigid 3,6‐dimethoxy‐9H‐carbazole moieties inBSA 50brings about improved hole mobility and higher work function compared to bis(4‐methoxyphenyl)amine units inBSA51, which increase interfacial hole transportation from perovskite to HTM. As a result, perovskite solar cells (PSCs) based onBSA50boost power conversion efficiency (PCE) to 22.65 %, and a PSC module usingBSA50HTM exhibits a PCE of 21.35 % (6.5×7 cm) with aVocof 8.761 V and FF of 79.1 %. The unencapsulated PSCs exhibit superior stability to devices employing spiro‐OMeTAD, retaining nearly 90 % of their initial efficiency after 1000 h operation output. This work demonstrates the high potential of molecularly engineered spirobi[acridine] derivatives as HTMs as replacements for spiro‐OMeTAD.
Complexed Semiconductor Cores Activate Hexaniobate Ligands as Nucleophilic Sites for Solar‐Light Reduction of CO2 by Water
Authors: Zhang Guanyun , Wang Fei , Tubul Tal , Baranov Mark , Leffler Nitai , Neyman Alevtina , Poblet Josep M. , Weinstock Ira A.
Published: October 2022

Although pure and functionalized solid‐state polyniobates such as layered perovskites and niobate nanosheets are photocatalysts for renewable‐energy processes, analogous reactions by molecular polyoxoniobate cluster‐anions are nearly absent from the literature. We now report that under simulated solar light, hexaniobate cluster‐anion encapsulated 30‐NiII‐ion “fragments” of surface‐protonated cubic‐phase‐like NiO cores activate the hexaniobate ligands towards CO2 reduction by water. Photoexcitation of the NiO cores promotes charge‐transfer reduction of NbV to NbIV, increasing electron density at bridging oxo atoms of Nb‐μ‐O‐Nb linkages that bind and convert CO2 to CO. Photogenerated NiO “holes” simultaneously oxidize water to dioxygen. The findings point to molecular complexation of suitable semiconductor “fragments” as a general method for utilizing electron‐dense polyoxoniobate anions as nucleophilic photocatalysts for solar‐light driven activation and reduction of small molecules.
Constructing Stable Anion‐Tuned Electrode/Electrolyte Interphase on High‐Voltage Na3V2(PO4)2F3 Cathode for Thermally‐Modulated Fast‐Charging Batteries
Authors: Deng Liang , Yu Fu‐Da , Sun Gang , Xia Yang , Jiang Yun‐Shan , Zheng Yin‐Qi , Sun Mei‐Yan , Que Lan‐Fang , Zhao Lei , Wang Zhen‐Bo
Published: October 2022

Constructing stable electrode/electrolyte interphase with fast interfacial kinetics is vital for fast‐charging batteries. Herein, we investigate the interphase that forms between a high‐voltage Na3V2(PO4)2F3 cathode and the electrolytes consisting of 3.0, 1.0, or 0.3 M NaClO4 in an organic carbonate solvent (47.5 : 47.5 : 5 mixture of EC: PC: FEC) during charging up to 4.5 V at 55 °C. It is found that a higher anion/solvent ratio in electrolyte solvation structure induces anion‐dominated interphase containing more inorganic species and more anion derivatives (CxClOy), which leads to a larger interfacial Na+ transport resistance and more unfavorable gas evolution. In comparison, a low anion/solvent ratio derives stable anion‐tuned interphase that enables better interfacial kinetics and cycle ability. Importantly, the performance of a failed cathode is restored by triggering the decomposition of CxClOy species. This work elucidates the role of tuning interphase in fast‐charging batteries.
Energy‐Efficient Iodine Uptake by a Molecular Host⋅Guest Crystal
Authors: Yang Xue , Li Chunyang , Giorgi Michel , Siri Didier , Bugaut Xavier , Chatelet Bastien , Gigmes Didier , Yemloul Mehdi , Hornebecq Virginie , Kermagoret Anthony , Brasselet Sophie , Martinez Alexandre , Bardelang David
Published: October 2022

Recently, porous organic crystals (POC) based on macrocycles have shown exceptional sorption and separation properties. Yet, the impact of guest presence inside a macrocycle prior to adsorption has not been studied. Here we show that the inclusion of trimethoxybenzyl‐azaphosphatrane in the macrocycle cucurbit[8]uril (CB[8]) affords molecular porous host⋅guest crystals (PHGC‐1) with radically new properties. Unactivated hydrated PHGC‐1 adsorbed iodine spontaneously and selectively at room temperature and atmospheric pressure. The absence of (i) heat for material synthesis, (ii) moisture sensitivity, and (iii) energy‐intensive steps for pore activation are attractive attributes for decreasing the energy costs. 1H NMR and DOSY were instrumental for monitoring the H2O/I2 exchange. PHGC‐1 crystals are non‐centrosymmetric and I2‐doped crystals showed markedly different second harmonic generation (SHG), which suggests that iodine doping could be used to modulate the non‐linear optical properties of porous organic crystals.
Stereo‐ and Site‐Selective Crotylation of Alcohol Proelectrophiles via Ruthenium‐Catalyzed Hydrogen Auto‐Transfer Mediated by Methylallene and Butadiene
Authors: Ortiz Eliezer , Spinello Brian J. , Cho Yoon , Wu Jessica , Krische Michael J.
Published: October 2022

Iodide‐bound ruthenium‐JOSIPHOS complexes catalyze the redox‐neutral C−C coupling of primary alcohols with methylallene (1,2‐butadiene) or 1,3‐butadiene to form products of anti‐crotylation with good to excellent levels of diastereo‐ and enantioselectivity. Distinct from other methods, direct crotylation of primary alcohols in the presence of unprotected secondary alcohols is possible, enabling generation of spirastrellolide B (C9–C15) and leucascandrolide A (C9–C15) substructures in significantly fewer steps than previously possible.
Long‐Range Interactions in Diatomic Catalysts Boosting Electrocatalysis
Authors: Li Wen‐Hao , Yang Jiarui , Wang Dingsheng
Published: October 2022

The simultaneous presence of two active metal centres in diatomic catalysts (DACs) leads to the occurrence of specific interactions between active sites. Such interactions, referred to as long‐range interactions (LRIs), play an important role in determining the rate and selectivity of a reaction. The optimal combination of metal centres must be determined to achieve the targeted efficiency. To date, various types of DACs have been synthesised and applied in electrochemistry. However, LRIs have not been systematically summarised. Herein, the regulation, mechanism, and electrocatalytic applications of LRIs are comprehensively summarised and discussed. In addition to the basic information above, the challenges, opportunities, and future development of LRIs in DACs are proposed in order to present an overall view and reference for future research.
Biosynthesis of Nodulisporic Acids: A Multifunctional Monooxygenase Delivers a Complex and Highly Branched Array
Authors: Richardson Alistair T. , Cameron Rosannah C. , Stevenson Luke J. , Singh A. Jonathan , Lukito Yonathan , Berry Daniel , Nicholson Matthew J. , Parker Emily J.
Published: October 2022

Nodulisporic acids (NAs) are structurally complex potent antiinsectan indole diterpenes. We previously reported the biosynthetic gene cluster for these metabolites in Hypoxylon pulicicidum and functionally characterised the first five steps of the biosynthetic pathway. Here we reveal a highly complex biosynthetic array, furnishing multiple end products through expression of cluster components in Penicillium paxilli. We show that seven additional cluster‐encoded gene products comprise the biosynthetic machinery that elaborate precursor NAF in this highly branched pathway. The combined action of these enzymes delivers 37 NA congeners including four major end products, NAA, NAA1, NAA2 and NAA4. The plethora of intermediates arises due to modification of the carboxylated prenyl tail by a single promiscuous P450 monooxygenase, NodJ, a pivotal branchpoint enzyme which produces four distinct biosynthetic products giving rise to the complex metabolic grid that characterises NA biosynthesis.
Structural design of poly(vinyl alcohol)/carbon fiber composite film used for antistatic packaging via asynchronous biaxial stretching
Authors: Wang Xuan , Zhang Huili , Li Li
Published: October 2022

Antistatic packaging film plays an important role in protecting sensitive electronic components from the damage of electrostatic discharge (ESD) during transportation and application. Considering the antistatic property and environmental friendliness of polyvinyl alcohol (PVA), PVA was chosen as matrix to prepare PVA/carbon fiber (CF) composite film via melt casting and asynchronous biaxial stretching. The addition of CF made more perfect conductive pathway formed in system, thus improving the electric property of the composite precursor sheet. And the subsequent biaxial stretching further promoted the cross arrangement of CF as well as the orientation of PVA molecular chains, so endowed the stretched composite film with excellent mechanical, antistatic and water‐resistant properties. When CF content was 5 wt% and the stretching ratio was 3.0 × 3.0, the tensile strength, volume resistivity and water contact angle of the composite film reached 69.4 MPa, 1.07 × 105 Ω·cm, and 74.7° respectively, which met the requirements of electrostatic dissipation packaging. This work highlights the structural evolution of PVA/CF composites under biaxial stretching and spurs the devising of antistatic packaging materials.
Optimization of mixing parameters on the degree of silanization using Taguchi and response surface method for fuel‐efficient tire tread compound
Authors: Neethirajan Jeevanandham , Natarajan Tamil Selvan , Velusamy Rajasekar , Patel Bharat , Krishnan S Rama , Naskar Kinsuk
Published: October 2022

Recently, in the tire industry, carbon black has been replaced by silica as a reinforcing filler for the development of “green tires”. The “green” claim comes from the fact that silica‐reinforced materials help further reduce rolling resistance, save vehicle fuel and reduce CO2 emissions to the environment. Silica‐silane technology dramatically contributes to the field tire industries by saving fuel. However, unlike carbon black mixing, silica mixing is complicated as it involves several reactions inside an internal mixer. In this paper, we have evaluated the effects of mixing parameters and optimized the silica‐filled elastomer compound using the design of experiments (Taguchi and Response surface method). Silanization temperature and time are found to be crucial parameters for silanization. Compounds mixed using optimized mixing parameters show superior performance properties compared to the control. Filler dispersion in the optimized batch was better and characterized using a scanning electron microscope (SEM). Tan δ @60°C as an indication of rolling resistance is improved by 23% indicating the better fuel economy of this system.
Hydrogel‐biochar composites for removal of methylene blue: Adsorption performance, characterization, and adsorption isotherm, kinetics, thermodynamics analysis
Authors: Wang Xiangpeng , Zheng Yunxiang , Zong Lina , Zhang Chunxiao
Published: October 2022

Low‐concentration organic dye wastewater severely threatens the growth and reproduction of animals and plants, as well as the survival and development of human beings and the environment. Although versatile hydrogel composites have been prepared owing to their excellent adsorption performance, the high‐removal efficiency and fast adsorption rate are still two crucial problems related to practical applications. Herein, xanthan gum‐g‐poly (acrylic acid‐co‐acrylamide)/biochar composite hydrogels with high‐removal efficiency and fast adsorption rate of methylene blue (MB) are synthesized using sodium dodecyl sulfate as a pore‐foaming agent. The composite hydrogels exhibit rough and porous three‐dimensional structures, which can make the internal active adsorption sites to be fully exposed and facilitate the MB diffusion process. MB's removal efficiency can reach 96.64% within 30 minutes, which is almost the first time that a biochar‐contained hydrogel could show superior removal efficiency of more than 95% in such a short adsorption time. The factors affecting the adsorption performance are studied comprehensively. Langmuir and pseudo‐second‐order models fit the adsorption process well. Moreover, the MB removal rate still exceeds 80% after eight cycles, which is also a vital indicator for practical treatment. Adsorption mechanism analysis shows that the synergistic effect among biochar, xanthan gum, and polymer chains and the porous structure improve the adsorption performance of the composite hydrogels. The proposed hydrogel‐biochar composites with high‐removal efficiency and adsorption rate are highly promising as an alternative adsorbent for advanced printing and dyeing wastewater treatment.
High oxygen barrier materials from paper to regenerated cellulose films
Authors: Jiang Baoqiang , Tang Yali , Zhou Keke , Lu Lixin , Qiu Xiaolin , Pan Liao
Published: October 2022

A transparent, bendable, high oxygen barrier cellulose‐based film was prepared, which has far better oxygen barrier properties than conventional polyethylene, polypropylene and cellophane materials. A series of regenerated cellulose films (RCs) were prepared from filter paper lacking oxygen barrier properties under different cellulose concentrations and gelation times. It was shown that the cellulose concentration and gel time had a greater effect on the oxygen barrier properties of RCs. When the cellulose concentration was 4 wt% and the gel time was 3 h, the RCs obtained the lowest oxygen permeability coefficient (OPC) down to 2.21 × 10−17 cm3 cm cm−2 s−1 Pa−1. The films have a tensile strength of 109.5 MPa, an elongation at break of 27.3% and a light transmission rate of 89%. In further, molecular dynamics simulations showed that when the filter paper was converted to RCs, the increase in hydrogen bonding and the decrease in free volume between cellulose chains caused a decrease in the diffusion coefficient of oxygen. As a novel biobased high oxygen barrier material, the film has broad application prospect in packaging and chemical industry.
Pilot‐scale comparison of granular activated carbons, ion exchange, and alternative adsorbents for per‐ and polyfluoroalkyl substances removal
Authors: Medina Ricardo , Pannu Manmeet W. , Grieco Scott A. , Hwang Michael , Pham Christine , Plumlee Megan H.
Published: October 2022

Eight granular activated carbons (GAC), four anion exchange (IX) resins, and two alternative adsorbents (AAs) were tested for the removal of per‐ and polyfluoroalkyl substances (PFAS) from a groundwater source used for drinking water. The study was conducted using pilot(meter)‐scale columns operated in continuous‐flow mode for 16–26 months. Comparison between GAC adsorbents showed that bituminous GACs exhibited higher adsorption than non‐/sub‐bituminous GACs. Testing of a reactivated and new GAC showed no significant differences with respect to PFAS adsorption. Of the four IX resins tested, one resin showed superior adsorption when compared with all three IX resins. A surface‐modified bentonite adsorbent showed superior removal efficiencies over all adsorbent types tested here. These results provide benchmark performance and adsorption capacities at pilot‐scale for various adsorbents and highlight the promise of AAs to remove PFAS from water sources with low (ng/L) concentrations.
Production of biocoal from wastewater sludge and sugarcane bagasse using hydrothermal carbonization
Authors: Mkhwanazi Zinhle , Isa Yusuf M.
Published: October 2022

The growing demand for fuel in South Africa coupled with the depletion of fossil fuel reserves demonstrates the need for alternative energy sources. A renewable resource such as biomass can be optimized as an energy source. Wastewater sludge and bagasse have the energy potential to produce high calorific value biocoal; this will contribute to the supply of energy in South Africa. The synthesis of biocoal from wastewater sludge and bagasse through an artificial synthetic coal production process, i.e. hydrothermal carbonization, is preferred over other thermal conversion techniques as hydrothermal carbonization is capable of handling feed having a high (75–90%) moisture content. In this study, wastewater sludge and sugarcane bagasse were subjected to hydrothermal carbonization, and the effect of temperature was explored at 180, 210, 240 and 260°C. Variation of the ratio of dry sludge to bagasse of 100:0, 80:20, 60:40, 40:60, 20:80 and 0:100 and the composition of solid to liquid (solid loading wt%) of 1:10, 2:10, 3:10 and 4:10 (SB:H2O) corresponding to 9.09, 16.67, 23.08 and 28.57 wt% loading was investigated. The results obtained in this study reveal that solid loading, temperature, biomass type and ratio variation had a substantial impact on the yield and calorific value of the biocoal produced. The highest biocoal yield of 23.36 wt% was achieved at 210°C and derived from sludge/bagasse with a sludge content of 20%. Across all of the runs, the highest calorific value of 20.21 MJ kg−1 was achieved at 260°C when pure bagasse was employed (0% sludge content). © 2022 The Authors. Biofuels, Bioproducts and Biorefining published by Society of Industrial Chemistry and John Wiley & Sons Ltd.
Delineating septo‐optic dysplasia
Authors: Lubinsky Mark , Encha‐Razavi Férechté
Published: October 2022

Background

Septo‐optic dysplasia (SOD), once a variable triad of septum pellucidum defects (SPDs), optic nerve hypoplasia (ONH), and hypopituitarism, has had multiple findings added, with uncertain causes, definitions, and limits.

Method

Literature review.

Results

SOD is a complex vascular sequence with confounders.

Conclusions

Proximal anterior cerebral artery trunk disruptions cause overlapping primary effects, giving ONH alone most often, and isolated SPD less. ONH disruptions can spread to pituitary, SPD disruptions to the cerebral cortex, causing schizencephaly and related anomalies. Pituitary defects are rare without ONH, and cortical findings are rare without SPD. Extensions are unidirectional, so isolated pituitary or cortical defects are separate from SOD. Micro‐ an‐ ophthalmia, a suggested ONH variant, is not part of SOD. Disruption by‐products can affect development, causing cognitive and endocrine issues, and structural anomalies such as corpus callosum thinning, ventriculomegaly, and hippocampal and olfactory findings. Limbic extensions may also contribute to the same structural defects as by‐products. Midline CNS developmental anomalies can act as disruptive foci, most likely through vascular variants, but have separate pathogenesis. Relative frequencies of specific pituitary hormone defects change as SOD rates increase. Increasing relative rates of midline CNS developmental defects and cortical anomalies are consistent with rising levels of exogenous exposures sensitizing to midline predispositions.
A fast fluorescent probe for tracing endoplasmic reticulum‐located carboxylesterase in living cells
Authors: Dai Xiaoyu , Yu Faqi , Jiang Zekun , Dong Baoli , Kong Xiuqi
Published: October 2022

Carboxylesterase (CEs), mainly localized in endoplasmic reticulum (ER), are responsible for hydrolyzing compounds containing various ester bonds. They have been closely associated with drug metabolism and cellular homeostasis. Although some CE fluorescent probes have been developed, there are still a lack of probes that could target to the ER. Here, we developed a novel fluorescent probe CR with a specific ER anchor for monitoring CEs. In CR, p‐toluenesulfonamide was chosen for precise ER targeting. A simple acetyl moiety was used as the CE response site and fluorescence modulation unit. During the spectral tests, CR displayed a fast response speed (within 10 s) towards CEs. In addition, it showed high sensitivity [limit of detection (LOD) = 5.1 × 10−3 U/ml] and high selectivity with CEs. In biological imaging, probe CR could especially locate in the ER in HepG2 cells. After cells were treated with orilistat, CR succeeded in monitoring the changes in the CEs. Importantly, CR also had the ability to trace the changes in CEs in a tunicamycin‐induced ER stress model. Therefore, probe CR could be a powerful molecular tool for further investigating the functions of CEs in the ER.
Targeting microglial NLRP3 in the SNc region as a promising disease‐modifying therapy for Parkinson's disease
Authors: Qiao Chen , Dang Tao , Zhou Yan , Zhou Yuan‐Zhang , Zhao Rong , Wang Min
Published: October 2022

Introduction

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic (DA) neurons. Accumulating evidence has shown that activation of the NLR family pyrin domain‐containing 3 (NLRP3) inflammasome is an early and cardinal feature in PD progression. Nevertheless, little is known about the effect of NLRP3 in the substantia nigra pars compacta (SNc) on DA neurodegeneration.

Methods and results

In the present study, we constructed NLRP3 interference sequences wrapped by lentivirus (LV3‐siNlrp3) to facilitate NLRP3 knockdown in the SNc region by intracerebral stereotactic injection. Then, we explored the effects of NLPR3 knockdown on PD pathologies via behavioral monitoring, immunohistochemistry and western blot analysis in acute 1‐methyl‐4‐phenyl‐1, 2, 3, 6‐tetrahydropyridine (MPTP) mouse model. Moreover, we performed in vitro experiments to investigate the effect of microglial NLRP3 knockdown on DA neuron survival in the context of 1‐methyl‐4‐phenylpyridinium (MPP+) stimulation. Our results demonstrated that NLRP3 knockdown in the SNc region significantly improved MPTP‐induced dyskinesia, DA neuronal loss and microglia activation in vivo. Meanwhile, knockdown of microglial NLRP3 attenuated MPP+‐induced DA neuronal damage in an indirect coculture system in which neurons were cultured in microglial conditional medium. Cumulatively, these data reveal that microglial NLRP3 located in the SNc region is detrimental to DA neurons survival, and knockdown of microglial NLRP3 is a potential strategy to rescue DA neurons in the progression of PD.

Conclusions

This work demonstrates the role of NLRP3 in PD pathogenesis via microglia‐neuron communication, and sheds light on targeting microglial NLRP3 to develop disease‐modifying therapy for PD.
Platelet membrane camouflaged AIEgen‐mediated photodynamic therapy improves the effectiveness of anti‐PD‐L1 immunotherapy in large‐burden tumors
Authors: Dai Jun , Wu Meng , Xu Yating , Yao Hongming , Lou Xiaoding , Hong Yuning , Zhou Jian , Xia Fan , Wang Shixuan
Published: October 2022

Although immunotherapy has achieved recent clinical success in antitumor therapy, it is less effective for solid tumors with large burdens. To overcome this challenge, herein, we report a new strategy based on platelet membrane‐camouflaged aggregation‐induced emission (AIE) luminogen (Plt‐M@P) combined with the anti‐programmed death ligand 1 (anti‐PD‐L1) for tumoral photodynamic‐immunotherapy. Plt‐M@P is prepared by using poly lactic‐co‐glycolic acid (PLGA)/PF3‐PPh3 complex as a nanocore, and then by co‐extrusion with platelet membranes. PF3‐PPh3 is an AIE‐active conjugated polyelectrolyte with photosensitizing capability for photodynamic therapy (PDT). Plt‐M@P exhibits superior tumor targeting capacity in vivo. When applied in small tumor‐bearing (~40 mm3) mice, Plt‐M@P‐mediated PDT significantly inhibits tumor growth. In tumor models with large burdens (~200 mm3), using Plt‐M@P‐mediated PDT or anti‐PD‐L1 alone is less effective, but the combination of both is effective in inhibiting tumor growth. Importantly, this combination therapy has good biocompatibility, as demonstrated by the absence of damage to the major organs, especially the reproductive system. In conclusion, we show that Plt‐M@P‐mediated PDT can improve anti‐PD‐L1 immunotherapy by enhancing antitumor effects, providing a promising strategy for the treatment of tumors with large burdens.
An integrated analysis of C5AR2 related to malignant properties and immune infiltration of gliomas
Authors: Huang Chengying , Qiu Ouwen , Mao Chaofu , Hu Zhicheng , Qu Shanqiang
Published: October 2022

Background

C5AR2 is recognized as a proinflammatory molecule and activates the inflammatory response in multiple disorders. However, little has been reported on C5AR2 in glioma. This study sought to explore its expression, biological function, and association with clinical pathological indicators, prognosis, and immune infiltration levels in glioma through glioma cohorts.

Methods

A cohort of 657 patients was screened from the Chinese Glioma Genome Atlas (CGGA). χ2 test was performed to calculate the difference of classified variables. Cox proportional hazard regression modeling was used to identify independent prognostic indicators of glioma patients. A survival plot was generated by the Kaplan–Meier method. The immune cell infiltration score of glioma patients was calculated by TIMER algorithm.

Results

We observed that high expression of C5AR2 was strongly associated with malignant clinical indicators in 657 patients with glioma, and patients with high C5AR2 expression had worse prognoses. Multivariate Cox analysis showed that C5AR2 could be a new independent prognostic indicator for glioma patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that C5AR2 overexpression correlated with multiple inflammatory and immune biological processes. Additionally, high C5AR2 expression was strongly associated with higher abundance and marker gene expression of multiple tumor immune cells in low‐grade glioma. Finally, a model was constructed to improve the prognostic evaluation of glioma patients.

Conclusions

The C5AR2 gene is highly expressed in gliomas and is significantly associated with clinical indicators of malignant progression in glioma patients. In glioma, patients with high C5AR2 expression displayed a worse outcome. In glioma tissues, the expression level of C5AR2 highly correlated with the abundance of tumor immune cell infiltration. Additionally, GO and KEGG enrichment analysis revealed that C5AR2 expression may be involved in a variety of immune and inflammatory biological processes.
Prognostic awareness and its association with health outcomes in the last year of life
Authors: Ozdemir Semra , Chaudhry Isha , Ng Sean , Teo Irene , Malhotra Chetna , Finkelstein Eric Andrew ,   COMPASS Study Group
Published: October 2022

Background

Little research has examined changes in prognostic awareness (PA) in the last year of life and the extent PA change was associated with anxiety, depression, and spiritual well‐being among metastatic cancer patients.

Methods

Two surveys were administered in the last year of life to 176 conveniently sampled Singaporean patients with stage 4 solid cancers. PA was assessed by asking patients whether they were aware that their treatments were unlikely to cure their cancer. Multivariable linear regression models were used to investigate the association of PA change with anxiety, depression, and spiritual well‐being.

Results

The proportion of patients with accurate PA increased (39.2%–45.5%; p < 0.05) from the second‐last assessment to the last assessment before death. Those with inaccurate PA decreased (26.1%–20.4%; p < 0.05) while a third of patients remained uncertain at both assessments (34.7% and 34.1%). Compared to patients with inaccurate PA at both assessments, patients who reported accurate PA at both assessments reported worsened anxiety (β = 2.08), depression (β = 3.87), and spiritual well‐being (β = −4.45) while patients who reported being uncertain about their prognosis at both assessments reported worsened spiritual well‐being (β = − 6.30) at the last assessment before death (p < 0.05 for all).

Conclusions

Interventions should dually focus on decreasing prognostic uncertainty at the end‐of‐life while minimising the psychological and spiritual sequelae associated with being prognostically aware. More research is needed to clarify the causes of prognostic uncertainty.
Cisplatin‐induced HSF1‐HSP90 axis enhances the expression of functional PD‐L1 in oral squamous cell carcinoma
Authors: Sasaya Takashi , Kubo Terufumi , Murata Kenji , Mizue Yuka , Sasaki Kenta , Yanagawa Junko , Imagawa Makoto , Kato Hirotaka , Tsukahara Tomohide , Kanaseki Takayuki , Tamura Yasuaki , Miyazaki Akihiro , Hirohashi Yoshihiko , Torigoe Toshihiko
Published: October 2022

Immune checkpoint inhibitor‐based cancer immunotherapy has provided an additional therapeutic option for oral squamous cell carcinoma (OSCC) with recurrence or distant metastases. However, further improvement of OSCC treatment is required to develop the optimal combination or order for chemoradiotherapy and immunotherapy. Along with the accumulation of clinical knowledge and evidence, it is also essential to clarify the biological impact of chemo‐radiotherapeutic agents on the cancer immune microenvironment. In this study, we investigated the effects of cisplatin (CDDP), a key therapeutic agent for OSCC, on programmed death‐ligand 1 (PD‐L1) expression in OSCC lines. Although CDDP treatment increased the surface levels of PD‐L1 on OSCC cell lines, the gene and total protein expression levels of PD‐L1 were not altered. We also demonstrated that the phosphorylation of heat shock factor 1 and heat shock protein 90 was involved in this process. In addition, CDDP‐induced PD‐L1 attenuated the target‐specific cytotoxic T lymphocyte reaction to OSCC. These results provide an immunobiological basis for the response of OSCC to CDDP and will contribute to our biological understanding of the action of novel combination therapy including immunotherapy together with platinum‐based chemotherapy for OSCC.
Inhibition of XPO1 impairs cholangiocarcinoma cell proliferation by triggering p53 intranuclear accumulation
Authors: Zhao Cheng , Ma Ben , Yang Zi‐yi , Li Ou , Liu Shi‐lei , Pan Li‐jia , Gong Wei , Dong Ping , Shu Yi‐jun
Published: October 2022

Background

XPO1 mediates the nuclear export of several proteins, mainly tumor suppressors. KPT‐330 (Selinexor) is a selective inhibitor of XPO1 that has demonstrated good therapeutic effects in hematologic cancers.

Methods

We used TCGA and GTEx pan‐cancer database to evaluate XPO1 mRNA expression in various tumors. Cell proliferation assay and colony formation assay were used to analyze the in vitro antitumor effects of XPO1 inhibitor KPT‐330. Western blot was performed to explore the specific mechanisms.

Results

We found that XPO1 was highly expressed across a range of cancers and associated with poor prognosis in hepatobiliary and pancreatic tumors. We revealed that the XPO1 inhibitor KPT‐330 triggered the nuclear accumulation of the p53 protein and significantly disrupted the proliferation of cholangiocarcinoma cells. Mechanistically, the XPO1 inhibitor, KPT‐330, reduced BIRC6 expression by inhibiting the PI3K/AKT pathway to decrease p53 degradation and improve its stability.

Conclusion

Therefore, XPO1 may be a potential therapeutic target in cholangiocarcinoma, mediated by its effects on KPT‐330.
RUNX2 interacts with SCD1 and activates Wnt/β‐catenin signaling pathway to promote the progression of clear cell renal cell carcinoma
Authors: Song Xiandong , Liu Junlong , Liu Bitian , Piao Chiyuan , Kong Chuize , Li Zhenhua
Published: October 2022

Background

Previous studies have demonstrated that Runt‐associated transcription factor 2 (RUNX2) serves as the main transcription factor for osteoblast differentiation and chondrocyte maturation. RUNX2 is related to a variety of tumors, particularly tumor invasion and metastasis, while the expression and molecular mechanisms of RUNX2 in clear cell renal cell carcinoma (ccRCC) keep to be determined. Stearyl CoA desaturase 1 (SCD1), an endoplasmic reticulum fatty acid desaturase, transfers saturated fatty acids to monounsaturated fatty acids, is expressed highly in numerous malignancies.

Methods

The Cancer Genome Atlas (TCGA) datebase and Western blot was used to analyzed the mRNA and protein levels of the target gene in ccRCC tissues and adjacent tissues. The proliferation ability of ccRCC cells was tested by colony forming and EdU assay. The migration ability of cells was detected by transwell assay. Immunoprecipitation was utilized to detect protein–protein interaction. Cycloheximide chase assay was used to measure the half‐life of SCD1 protein.

Results

In this study, the expressions of RUNX2 and SCD1 are increased in ccRCC tissues as well as ccRCC cell lines. Both RUNX2 and SCD1 could promote proliferation and migration in ccRCC cells. Furthermore, RUNX2 could physically interact with SCD1. In addition, the functional degradation and the inactivation of Wnt/β‐catenin signaling pathway triggered by the downregulation of RUNX2 could be partly offset by the overexpression of SCD1.

Conclusion

The findings indicate that the RUNX2/SCD1 axis may act as a potential therapeutic target via the Wnt/β‐catenin signaling pathway of ccRCC.
Lignans and Flavonoids from Cajanus cajan (L.) Millsp. and Their α‐Glucosidase Inhibitory Activities
Authors: Lei Xin‐Yu , Liu Shao‐Huan , Zhao Ya‐Xian , Guo Meng‐Jia , Tao Ling , Shen Xiang‐Chun , Zhang Nen‐Ling
Published: October 2022

A pair of new lignan conformers (1–2), one new flavonoid glycoside (3), as well as nineteen known compounds were purified from the twigs and leaves of Cajanus cajan (L.) Millsp.. The planar structures of the unknown compounds were determined via NMR and high‐resolution mass spectrometry, while their absolute configurations were elucidated via comparison between their experimental and calculated electronic circular dichroism (ECD) values. All the isolated compounds were assayed for their α‐glucosidase inhibitory activities. The results demonstrated that compounds 8–12, 15–16, 18–19, 21–22 had strong inhibition activities, with compound 10 (IC50=0.4±0.21 μM) most active. The structure‐activity relationships were preliminarily summarized. Enzyme kinetics showed that compounds 8, 9, 15–16, 18–19, 21–22 were non‐competitive inhibitors and compounds 10–12 were anti‐competitive ones.
Anticholinesterase Compounds from Endemic Prangos uechtritzii
Authors: Albayrak Gokay , Demir Serdar , Koyu Halil , Baykan Sura
Published: October 2022

In this study, the anticholinesterase effects of the extracts and isolated compounds from the roots of endemic Prangos uechtritzii Boiss & Hausskn (Apiaceae) are reported. A novel polyacetylenic compound; (+)‐8‐O‐methyloplopantriol A along with two known polyacetylenes; (−)‐panaxynol, (+)‐falcarindiol and fifteen known coumarin derivatives; umbelliferone, 6‐formylumbelliferone, suberosin, 7‐demethylsuberosin, (+)‐ulopterol, tamarin, psoralen, imperatorin, (+)‐oxypeucedanin, (+)‐oxypeucedanin hydrate, (+)‐oxypeucedanin methanolate, (+)‐marmesin, (−)‐prantschimgin, (+)‐decursinol, and (−)‐adicardin were isolated from the hexane (Pu‐HE), chloroform (Pu‐CE), and methanol (Pu‐ME) extracts of P. uechtritzii roots. (−)‐Panaxynol, (+)‐falcarindiol, 6‐formylumbelliferone, (+)‐decursinol, and (−)‐adicardin were obtained from the genus Prangos for the first time. (+)‐8‐O‐Methyloplopantriol A inhibited both AChE (IC50=194.5±5.8 μM) and BChE (IC50=51.9±2.96 μM) enzymes. (+)‐Falcarindiol, 6‐formylumbelliferone, 7‐demethylsuberosin, tamarin, and imperatorin also exhibited BChE‐specific inhibitory activities (IC50=27.88‐93.86 μM). (+)‐Falcarindiol (IC50=27.88±0.91 μM) and imperatorin (IC50=30.89±1.40 μM) as the most active components could be led compounds to develop new BChE inhibitors with further research against Alzheimer's disease.
Recent Advances towards the Reversible Chemical Modification of Proteins
Authors: Wu Chuan‐Shuo , Cheng Liang
Published: October 2022

Proteins are intriguing biomacromolecules for all living systems, not only as essential building blocks of organisms, but also as participants in almost every aspect of cellular activity such as metabolism and gene transcription/expression. Developing chemical biology tools that are capable of labeling/modifying proteins is a powerful method for decoding their detailed structures and functions. However, most current approaches heavily rely on the installation of permanent tags or genetic engineering of unnatural amino acids. There has been slow development in reversible chemical labeling using small organic probes and bioorthogonal transformations to construct site‐selectively modified proteins and conditionally restore their activities or structures. This review summarizes recent advances in the field of chemical regulation of proteins with reversible transformations towards distinct motifs, including amino acid residues, amide backbones and native post‐translational lysine. Finally, current challenges and future perspectives are discussed.