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The nonselective calcium‐permeable Transient Receptor Potential Cation Channel Subfamily V Member4 (TRPV4) channel regulates various physiological activities. Dysfunction of TRPV4 is linked to many severe diseases, including edema, pain, gastrointestinal disorders, lung diseases, and inherited neurodegeneration. Emerging TRPV4 antagonists show potential clinical benefits. However, the molecular mechanisms of TRPV4 antagonism remain poorly understood. Here, cryo‐electron microscopy (cryo‐EM) structures of human TRPV4 are presented in‐complex with two potent antagonists, revealing the detailed binding pockets and regulatory mechanisms of TRPV4 gating. Both antagonists bind to the voltage‐sensing‐like domain (VSLD) and stabilize the channel in closed states. These two antagonists induce TRPV4 to undergo an apparent fourfold to twofold symmetry transition. Moreover, it is demonstrated that one of the antagonists binds to the VSLD extended pocket, which differs from the canonical VSLD pocket. Complemented with functional and molecular dynamics simulation results, this study provides crucial mechanistic insights into TRPV4 regulation by small‐molecule antagonists, which may facilitate future drug discovery targeting TRPV4. [ABSTRACT FROM AUTHOR]

Plasmonic metasurfaces can significantly enhance the interaction between light and 2D materials. Hybrid structures of plasmonic lattices and 2D materials show great promise for both fundamental and practical studies because of their unprecedented ability for precise manipulation of light at the nanoscale. This review starts with an overview of the basic concepts of plasmonic lattices and optical properties of 2D materials, as well as fabrication strategies for hybrid metasurfaces. Then, the enhanced photoluminescence, quantum emission, optoelectronic detection, nonlinear process, and valleytronics in hybrid metasurfaces are summarized, and their development for nanophotonic functional devices are reviewed. Further, several compelling topics are also outlined that provide outlooks for future directions of hybrid metasurfaces such as novel structural design and high‐quality fabrication, all‐dielectric metasurfaces, dynamic metasurfaces, and plasmonic mediation of chemical reactions and physical processes. It is believed that hybrid metasurfaces of plasmonic lattices and 2D materials can open prospects for versatile platforms for light‐matter interactions and contribute to the revolutions on nanophotonic devices. [ABSTRACT FROM AUTHOR]

The Asian citrus psyllid, Diaphorina citri Kuwayama, is among the most important pests of citrus. It is the main vector of the Huanglongbing (HLB) pathogen Candidatus Liberibacter asiaticus (CLas), which causes severe losses in citrus crops. Control of D. citri is therefore of paramount importance to reduce the spread of HLB. In this regard, using RNA interference (RNAi) to silence target genes is a useful strategy to control psyllids. In this study, using RNAi, we examined the biological functions of the V‐ATPase subunit E (V‐ATP‐E) gene of D. citri, including its effect on acquisition of CLas. The amino acid sequence of V‐ATP‐E from D. citri had high homology with proteins from other insects. V‐ATP‐E was expressed at all D. citri life stages analyzed, and the expression level in mature adults was higher than that of teneral adults. Silencing of V‐ATP‐E resulted in a significant increase in mortality, reduced body weight, and induced cell apoptosis of the D. citri midgut. The reduced expression of V‐ATP‐E was indicated to inhibit CLas passing through the midgut and into the hemolymph, leading to a majority of CLas being confined to the midgut. In addition, double‐stranded RNA of D. citri V‐ATP‐E was safe to non‐target parasitic wasps. These results suggest that V‐ATP‐E is an effective RNAi target that can be used in D. citri control to block CLas infection. [ABSTRACT FROM AUTHOR]

The development of multicomponent ligands to improve catalytic reactivity and selectivity remains a significant challenge for the synthesis of chiral building blocks. Here, a modular synthesis of structurally diverse multiligated platinum complexes, characterized by X‐ray crystallography, was revealed to open up a previously inaccessible reaction space. A library of more than 16 binary component‐ligated platinum complexes was identified as a practical toolkit to enable faster screening. The isolated bench‐stable PtII(oxazoline)(phosphine) complex paired with a chiral copper complex exhibits fundamentally new cooperative reactivity. The newly designed Pt/Cu dual catalytic system contributed to the development of highly enantioselective vinylogous addition reactions between a Pt‐activated electrophilic α,β‐unsaturated carbene and a Cu‐activated nucleophile, resulting in a reliable process for the asymmetric synthesis of valuable functionalized indoles in good yields and excellent enantioselectivities. [ABSTRACT FROM AUTHOR]

The development of multicomponent ligands to improve catalytic reactivity and selectivity remains a significant challenge for the synthesis of chiral building blocks. Here, a modular synthesis of structurally diverse multiligated platinum complexes, characterized by X‐ray crystallography, was revealed to open up a previously inaccessible reaction space. A library of more than 16 binary component‐ligated platinum complexes was identified as a practical toolkit to enable faster screening. The isolated bench‐stable PtII(oxazoline)(phosphine) complex paired with a chiral copper complex exhibits fundamentally new cooperative reactivity. The newly designed Pt/Cu dual catalytic system contributed to the development of highly enantioselective vinylogous addition reactions between a Pt‐activated electrophilic α,β‐unsaturated carbene and a Cu‐activated nucleophile, resulting in a reliable process for the asymmetric synthesis of valuable functionalized indoles in good yields and excellent enantioselectivities. [ABSTRACT FROM AUTHOR]

Garnet‐based solid‐state Li‐metal batteries (GSSBs) have the merits of high energy density and high safety. However, the realization of a stable and well‐matched Li|garnet interface for GSSBs remains challenging due to electron leakage and lithiophobic Li2CO3 impurity. To address these issues, herein, new surface chemistry is reported that converts the undesired Li2CO3 contaminant into an ultra‐thin lithium polyphosphate (Li‐PPA) layer through anhydrous polyphosphoric acid ‐induced in situ substitution reaction without damaging the water‐sensitive garnet electrolyte. In particular, the Li‐PPA interlayer not only facilitates the homogenous spreading of molten Li but also creates a robust electron‐blocking shield to suppress Li dendrite formation. As a result, the assembled Li symmetric cell exhibits a low interfacial impedance (4 Ω cm2) and high critical current density (1.8 mA cm−2) at 25 °C, which enables the cell to continuously cycle over 2500 h at 0.2 mA cm−2. Furthermore, the GSSBs paired with LiFePO4 deliver a high capacity of 149.3 mAh g−1 at 1 C and maintain 92.3% of the initial capacity after 500 cycles and can be used for solar energy storage, suggesting the feasibility of this interfacial engineering strategy for GSSBs. [ABSTRACT FROM AUTHOR]

Diarylamines and related scaffolds are ubiquitous atropisomeric chemotypes in biologically active natural products. However, the catalytic asymmetric synthesis of these axially chiral compounds remains largely unexplored. Herein, we report that a BINOL‐derived chiral phosphoric acid (CPA) successfully catalyzed the atroposelective coupling of quinone esters and anilines through direct C−N bond formation to afford N‐aryl quinone atropisomers with an unprecedented intramolecular N−H−O hydrogen bond within a six‐membered ring in good yields and enantioselectivities with the quinone ester as both the electrophile and the oxidant. A gram‐scale experiment demonstrated the utility of this synthetic protocol. Moreover, this methodology provides a platform for the synthesis of structurally diverse secondary amine atropisomers by nucleophilic addition. [ABSTRACT FROM AUTHOR]

Diarylamines and related scaffolds are ubiquitous atropisomeric chemotypes in biologically active natural products. However, the catalytic asymmetric synthesis of these axially chiral compounds remains largely unexplored. Herein, we report that a BINOL‐derived chiral phosphoric acid (CPA) successfully catalyzed the atroposelective coupling of quinone esters and anilines through direct C−N bond formation to afford N‐aryl quinone atropisomers with an unprecedented intramolecular N−H−O hydrogen bond within a six‐membered ring in good yields and enantioselectivities with the quinone ester as both the electrophile and the oxidant. A gram‐scale experiment demonstrated the utility of this synthetic protocol. Moreover, this methodology provides a platform for the synthesis of structurally diverse secondary amine atropisomers by nucleophilic addition. [ABSTRACT FROM AUTHOR]

Triterpene scaffolds are cyclized by differential functional genes of the oxidosqualene cyclase (OSC) gene family, which are widely present in plant species. Thirty‐nine OSCs were identified from the hexaploid bread wheat (Triticum aestivum L.) genome. The gene structure organization and the distribution of conserved motifs of OSCs gene family revealed that the TaOSC proteins are highly conserved. By phylogenetic analysis, all OSC proteins from wheat and other cereal crops were clustered into 11 subfamilies (I–XI). Based on the publicly available transcriptional profiling, the tissue‐specific expression patterns of TaOSC during several developmental stages revealed diverged expression patterns, indicating that the TaOSC family has undergone subfunctionalization. Furthermore, homeolog expression bias was commonly detected in the TaOSC subfamilies, such as the expression of Ta5A004900 and Ta5D011800 in the subfamily II were specifically expressed in the leaf sheath and flag leaf sheath. In addition, two genes were strongly induced by Pst, indicating that the two homolog genes are involved in the resistance to powdery mildew. Molecular evolution analysis indicated that the TaOSC family genes were undergone purifying selection. So, the powdery mildew response may be very conservative and important biological function of the Ta5A004900 and Ta5D011800 in wheat. In conclusion, these results can be used to explore the diversity of triterpenes and clarify the mechanism of triterpene cyclization, and also provide useful information for future studies on the function of the TaOSC gene family in bread wheat and other important crops. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to compare the percutaneous oblique osteotomy (POO) and the open chevron osteotomy technique for correction of hallux valgus deformity at a 2‐year follow‐up. Methods: This is a retrospective study of consecutive patients undergoing operative correction of hallux valgus using one of two techniques (POO vs open chevron osteotomy) from 2014 to 2018. Forty eight feet (41 patients) that underwent the POO was compared with 64 feet (58 patients) that underwent open chevron osteotomy. The hallux valgus angle (HVA), intermetatarsal angle (IMA) and American Orthopedic Foot & Ankle Society Hallux Metatarsophalangeal‐Interphalangeal scores (AOFAS‐HMI) were assessed preoperatively and postoperatively at the 1, 2‐year follow‐up. The Manchester–Oxford Foot Questionnaire (MOXFQ) were assessed preoperatively and postoperatively at the 2‐year follow‐up. The VAS score was collected preoperatively and on 2 weeks,1 year and 2‐year follow‐up. Results: Both groups achieved significant correction of the hallux deformity. The HVA in the POO group during the follow‐up period were 12.5 ± 2.22 and 17.9 ± 9.31, respectively, and in the open chevron group were 14.1 ± 6.78 and 14.8 ± 7.83, respectively. The IMA in the POO group during the follow‐up period were 7.61 ± 1.63 and 6.94 ± 1.53, respectively, and in the open chevron group were 6.89 ± 3.06 and 6.97 ± 2.95, respectively. Postoperative MOXFQ scores in all domains were significantly improved in both groups, however there was no significant difference in the improvement of any domain between POO and open groups at a 2‐year follow‐up. The AOFAS HMI scores in the POO group during the follow‐up period were 86.5 ± 10.7 and 85.2 ± 13.8, respectively, and in the open chevron group were 88.2 ± 10.8 and 79.5 ± 23.7, respectively. The VAS scores in the POO group during the follow‐up period were 2.00 ± 0.98, 2.00 ± 0.99 and 1.55 ± 1.11, respectively, and in the open chevron group were 5.51 ± 1.45, 2.56 ± 2.88 and 2.56 ± 2.88 respectively. The 1‐year and 2‐year follow‐up outcomes between POO and open groups showed no significant difference regarding AOFAS HMI scores and VAS scores, however the POO group showed statistically significant improvement of VAS scores in the postoperative 2 weeks (P < 0.001). There was no statistical significance between the POO and open group in terms of complications rates (8.3% vs 12.5%, P = 0.480). Conclusion: The POO technique is reliable and shows a comparable outcome to the open chevron osteotomy. However, the POO technique shows significantly less pain in the first 2 weeks after surgery. [ABSTRACT FROM AUTHOR]

BACKGROUND: Alcoholic liver disease (ALD) refers to liver damage caused by long‐term heavy drinking, which causes oxidative stress and changes in gut microbiota. In this paper, we investigated the hepatoprotective effect of sea buckthorn fermentation liquid on ALD in mice and the interaction between ALD and gut microbiota using animal experiments and gut microbiota measurements. RESULTS: We found that the contents of total flavonoids, total triterpenes and related short‐chain fatty acids (SCFAs) in sea buckthorn fermentation liquid (SFL) were significantly greater. Liver index, kidney index, spleen index, serum indexes of liver injury – alanine aminotransferase (ALT) and spartate aminotransferase (AST), inflammatory factors in liver tissues – tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6), oxidation indexes – malondialdehyde (MDA) and superoxide dismutase (SOD), and lipid metabolism indexes – high‐density liptein cholesterol (HDL‐C), low density lipoprotein cholesterol (LDL‐C), and triglyceride (TG), suggested that SFL significantly ameliorates liver injury caused by alcohol. By measuring gut microbiota in mice feces samples, we found that the high‐dose group of SFL reversed the declining trend of the gut microbiota Firmicutes/Bacteroidetes (F/B) ratio caused by alcohol, reducing the number of gram‐negative bacteroidetes. Patescibacteria was tightly connected with the indicators of ALD. At the genus level, high‐dose SFL significantly downregulated Akkermansia, Turicibacter, Alistipes and Ruminiclostridium, and improved the abundance of beneficial bacteria in Lactobacillus. In addition, Alistipes and Ruminiclostridium was closely connected with the indicators of ALD. CONCLUSION: Sea buckthorn fermentation liquid protected against alcoholic liver disease and modulated the composition of gut microbiota. © 2020 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Sedentary and high‐calorie diets are associated with increased risk of obesity and type 2 diabetes mellitus, while exercise and diet control are also important nondrug treatments for diabetes. Fibroblast growth factor 21 (FGF21) is an important cytokine, which is mainly expressed in liver, fat and muscle tissue responding to nutrition and exercise, and plays an important role in the improvement of glucose and lipid metabolism. Due to the increasing serum FGF21 level in obesity and diabetes, FGF21 can be used as a predictor or biomarker of diabetes. A variety of clinical antidiabetic drugs can reduce the content of FGF21, possibly for the improvement of FGF21 sensitivity. In this paper, we reviewed the interactions between FGF21 and nondrug therapy (diet and exercise) for diabetes and explored the potential value of the combined application of clinical antidiabetic drugs and FGF21. [ABSTRACT FROM AUTHOR]

Purpose: High‐resolution magnetic resonance imaging (HR‐MRI) has high spatial resolution and can simultaneously perform wall and lumen imaging. Dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) can evaluate the integrity of the blood–brain barrier. In this paper, the result of 3.0T HR‐MRI and 3.0T DCE‐MRI has been evaluated to explore the application value of unilateral middle cerebral artery inflammatory stenosis and changes in vascular permeability parameters of stroke events. Methods: Thirty‐six cases of neurological suspicion of central nervous system vasculitis of our hospital were selected from 20 January 2018 to 1 January 2019, who were diagnosed as unilateral middle cerebral artery M1 stenosis/occlusion by 3D TOF MRA. 3.0T HR‐MRI and 3.0T DCE‐MRI has been applied. Results: Among the 36 patients who met the inclusion criteria, 23 patients with central nervous system vasculitis were diagnosed. The 23 patients with HR‐MRI showed diffuse thickening and enhanced stenosis. The Ktrans value of 10/23 patients with acute–subacute cerebral infarction and 3/23 patients in chronic phase were significantly higher than that of the mirror side, and the Ktrans value of these patients remeasured in the same region of interest is lower than before after 6 months treatment. The Ktrans value in the target area of 10 patients without cerebrovascular events was not statistically significant compared with the mirror side. The Ktrans value of patients with acute–subacute cerebral infarction was significantly higher than that without cerebrovascular events (0.098 ± 0.038 vs. 0.007 ± 0.001, p =.000), and there was no significant difference between Ktrans in the chronic infarction group and the other two groups (0.098 ± 0.038 vs. 0.044 ± 0.012, p =.058; 0.044 ± 0.012 vs. 0.007 ± 0.001, p =.057). Conclusion: HR‐MRI is an accurate direct imaging method and has a high value for the etiological diagnosis of central nervous system vasculitis. DCE‐MRI could be an effective way to evaluate and monitor blood–brain barrier to prevent clinical ischemic stroke. [ABSTRACT FROM AUTHOR]

In this paper, we obtain interior Hölder continuity for solutions of the fourth‐order elliptic system Δ2u=Δ(V·∇u)+div(w∇u)+W·∇uformulated by Lamm and Rivière [Comm. Partial Differential Equations 33 (2008) 245–262]. Boundary continuity is also obtained under a standard Dirichlet or Navier boundary condition. We also use conservation law to establish a weak compactness result which generalizes a result of Rivière for the second‐order problem. [ABSTRACT FROM AUTHOR]

Chiral phosphines were found to catalyze the enantioselective asymmetric γ‐addition of heteroaromatic compounds to allenoates in good yields with high enantiomeric ratios and regioselectivity in the presence of (S)‐BINOL. Both pyrazole and imidazole could be employed in this process. The synthetic value of these γ‐addition products was demonstrated by the preparation of biologically relevant molecules and structural scaffolds. Remarkably, the synthetic utility of this strategy was demonstrated through a two‐step synthesis of a Janus kinase (JAK) inhibitor. Value added: A highly efficient γ‐addition reaction was developed that gives high yields with excellent enantiomeric ratios by using a phosphine catalyst system. The synthetic utility of this strategy is demonstrated by the preparation of biologically relevant molecules such as a Janus kinase (JAK) inhibitor. [ABSTRACT FROM AUTHOR]

Chiral phosphines were found to catalyze the enantioselective asymmetric γ‐addition of heteroaromatic compounds to allenoates in good yields with high enantiomeric ratios and regioselectivity in the presence of (S)‐BINOL. Both pyrazole and imidazole could be employed in this process. The synthetic value of these γ‐addition products was demonstrated by the preparation of biologically relevant molecules and structural scaffolds. Remarkably, the synthetic utility of this strategy was demonstrated through a two‐step synthesis of a Janus kinase (JAK) inhibitor. [ABSTRACT FROM AUTHOR]

Multimodal imaging techniques have been demonstrated to be greatly advantageous in achieving accurate diagnosis and gained increasing attention in recent decades. Herein, we present a new strategy to integrate the complementary modalities of 19F magnetic resonance imaging (19F MRI) and fluorescence imaging (FI) into a polymer nanoprobe composed of hydrophobic fluorescent organic core and hydrophilic fluorinated polymer shell. The alkyne-terminated fluorinated copolymer (P n) of 2,2,2-trifluoroethyl acrylate (TFEA) and poly(ethylene glycol) methyl ether acrylate (PEGA) was first prepared via atom transfer radical polymerization (ATRP). The PEGA plays an important role in both improving 19F signal and modulating the hydrophilicity of P n. The alkynyl tail in P n is readily conjugated with azide modified tetra-phenylethylene (TPE) through click chemistry to form azo polymer (TPE-azo-P n). The core-shell nanoprobes (TPE-P3N) with an average particle size of 57.2 ± 8.8 nm are obtained via self-assembly with ultrasonication in aqueous solution. These nanoprobes demonstrate high water stability, good biocompatibility, strong fluorescence and good 19F MRI performance, which present great potentials for simultaneous fluorescence imaging and 19F-MR imaging. [ABSTRACT FROM AUTHOR]

The pentadentate amine-bis(phenolate) ligand 6,6'-(dipyridin-2-ylmethylazanediyl)bis(methylene)bis(2,4-dimethylphenol) (H2L) was prepared and characterized. This ligand readily coordinates with FeIII or CoIII ions, and the resulting complexes [FeIIILCl] (1) and [CoIIIL(H2O)]Cl (2) were characterized by elemental analysis. X-ray structural studies show that the ligand in complexes 1 and 2 acts as a pentadentate ligand, leaving one coordination side of the transition metal available for exogenous ligands such as chloride ion (1) or water (2) ligand, and the central metal atoms are hexacoordinate in a similar distorted octahedral arrangement. Electrochemical studies reveal that each of the complexes exhibits multiple redox processes in the potential window investigated. Complex 1 shows one reversible oxidative event at 0.32 V and one quasi-reversible reduction event at -1.03 V, while the complex 2 displays one reversible oxidative event at 0.18 V and one quasi-reversible reduction at -0.64 V. [ABSTRACT FROM AUTHOR]

Objective To investigate the characteristics and the results of realignment surgery for the treatment of malunited ankle fracture. Methods Thirty-three patients with malunited fractures of the ankle who underwent reconstructive surgery at our hospital from January 2010 to January 2014 were reviewed. The tibial anterior surface angle ( TAS), the tibiotalar tilt angle ( TTA), the malleolar angle ( MA), and the tibial lateral surface angle ( TLS) were measured. Clinical assessment was performed with use of the American Orthopaedic Foot and Ankle Society ( AOFAS) scale and visual analogue scale ( VAS) scores, and the osteoarthritis stage was determined radiographically with the modified Takakura classification system. The Wilcoxon matched-pairs test was used to analyze the difference between the preoperative and the postoperative data. Results The mean follow-up was 36 months (range, 20-60 months). The mean age at the time of realignment surgery was 37.1 years (range, 18-62 years). Compared with preoperation, the TAS at the last follow-up showed a significant increase (88.50° ± 4.47° vs. 90.80° ± 3.49°, P = 0.0035); similar results were observed in TTA (1.62° ± 1.66° vs. 0.83° ± 0.90°, P < 0.01) and MA (82.30° ± 8.03° vs. 78.70° ± 4.76°, P = 0.005). At the last follow-up, the mean AOFAS score was significantly increased compared with the score at preoperation (44.5 ± 13.7 vs. 78.0 ± 8.9, P < 0.01). Significant differences in VAS scores were found at the last follow-up (6.76 ± 1.03 vs. 2.03 ± 1.21, P < 0.01). There was no significant difference in the Takakura grade between the preoperation and the last follow-up. One patient had increased talar tilt postsurgery; the postoperative talar tilt angle of this patient was 20°. One patient had progressive ankle osteoarthritis, and was treated by ankle joint distraction. Conclusions Realignment surgery for a malunited ankle fracture can reduce pain, improve function, and delay ankle arthrodesis or total ankle replacement. Postoperative large talar tilt and advanced stages of ankle arthritis are the risk factors for the surgery. [ABSTRACT FROM AUTHOR]

Aim: We designed a jaundice colour card that could be used by the parents of neonates and validated it by comparing it with total serum bilirubin levels.Methods: There were 106 term Chinese neonates in the study. The majority weighed between 2500 g and 3499 g (63%) and had a gestational age of 37-40 weeks (77%). The jaundice colour card and photometric determination were used to screen for neonatal jaundice and compared with serum bilirubin.Results: The bilirubin levels were measured by mothers using the jaundice colour card, and 67% of the measurements were taken at 11-20 days (range 3-30). The measurements at the infant's forehead, cheek and sternum showed strong correlations with total serum bilirubin. The mean differences between the total serum bilirubin and the jaundice colour card measurements from the forehead, cheek and sternum were 1.9 mg/dL, 0.3 mg/dL and 1.5 mg/dL, respectively. When total serum bilirubin >13 mg/dL was used as the cut-off point, the areas under the receiver operating characteristics curves were 0.934 for the forehead, 0.985 for the cheek and 0.966 for the sternum.Conclusion: We established the validity of the jaundice colour card as a parental measurement tool for jaundice in Chinese neonates, and the cheek was the best measurement site. [ABSTRACT FROM AUTHOR]

Objective To establish the colonic expression quantitative trait locus map in Han Chinese population and provide a functional reference for interpreting genetic associations of diseases such as inflammatory bowel disease (IBD). Methods Colonic mucosal biopsies and peripheral blood samples were obtained from 48 Chinese Han individuals (24 ulcerative colitis patients and 24 healthy controls). Transcription profiling was performed using human whole genome expression array. Genotyping was done using a population-specific genotype array. Imputation was performed using IMPUTE2. Association between genotypes and gene expression was analyzed using a Matrix Expression Quantitative Trait Loci (eQTL) R package to identify eQTL. We used ChIPpeakAnno R package for annotation of the eQTL. Linkage disequilibrium between the eQTL and IBD risk loci was also investigated. Results We identified 6 377 single nucleotide polymorphism-transcript interactions ( cis-eQTL) in the colon of the Chinese participants. Most of the eQTL located near the transcription starting sites and overlapped with histone modification marks on the genome. A significant proportion of the eQTL were found to be within transcription factor-binding sites. Two IBD risk loci were found to be colon cis-eQTL in Chinese individuals, and 51 cis-eQTL were identified in another 18 IBD risk loci. Conclusions This study defined a population-specific catalogue of colon eQTL in the Chinese population. Potential functional variants of IBD association signals were identified. We provided a useful reference dataset for fine mapping IBD risk loci and identifying causal variants in the Chinese Han population. [ABSTRACT FROM AUTHOR]

Perylene diimides (PDIs) are one of the most widely studied n-type materials, showing great promise as electron acceptors in organic photovoltaic devices and as electron transport materials in n-channel organic field effect transistors. Amongst the well-established chemical modification strategies for increasing the electron mobility of PDI, substitution of the imide oxygen atoms with sulfur, known as thionation, has remained largely unexplored. In this work, it is demonstrated that thionation is a highly effective means of enhancing the electron mobility of a bis- N-alkylated PDI derivative. Successive oxygen-sulfur substitution increases the electron mobility such that the fully thionated derivative ( S4) has an average mobility of 0.16 cm2 V−1 s−1. This is two orders of magnitude larger than the nonthionated parent compound ( P), and is achieved by solution deposition and without thermal or solvent vapor annealing. A combination of atomic force microscopy and 2D wide angle X-ray scattering experiments, together with theoretical modeling of charge transport efficiency, is used to explain the strong positive correlation observed between electron mobility and degree of thionation. This work establishes thionation as a highly effective means of enhancing the electron mobility of PDI, and provides motivation for the development of thionated PDI derivatives for organic electronics applications. [ABSTRACT FROM AUTHOR]

Structural equation models (SEMs) are widely recognized as the most important statistical tool for assessing the interrelationships among latent variables. This study develops a Bayesian adaptive group least absolute shrinkage and selection operator procedure to perform simultaneous model selection and estimation for semiparametric SEMs, wherein the structural equation is formulated using the additive nonparametric functions of observed and latent variables. We propose the use of basis expansions to approximate the unknown functions. By introducing adaptive penalties to the groups of basis expansions, the nonlinear, linear, or non-existent effects of observed and latent variables in the structural equation can be automatically detected. A simulation study demonstrates that the proposed method performs satisfactorily. This paper presents an application of revealing the observed and latent risk factors of diabetic kidney disease. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A highly enantioselective N-heterocyclic carbene (NHC) catalyzed formal [3+2] annulation of α,β-unsaturated aldehydes with azaaurones or aurone generating spiro-heterocycles has been developed. The protocol represents a unique NHC-activation-based approach to access spiro-heterocyclic derivatives bearing a quaternary stereogenic center with high optical purity (up to 95 % ee). [ABSTRACT FROM AUTHOR]

Eine hoch enantioselektive, durch N-heterocyclische Carbene (NHC) katalysierte formale [3+2]-Anellierung von α,β-ungesättigten Aldehyden mit Azaauronen oder Auron wurde entwickelt, die Spiroheterocyclen liefert. Dieses Protokoll stellt einen einzigartigen Zugang zu Spiroheterocyclen mit quartärem Stereozentrum dar. [ABSTRACT FROM AUTHOR]

Purpose: Despite the significant physical differences between magnetic resonance imaging (MRI) and computed tomography (CT), the high entropy of MRI data indicates the existence of a surjective transformation from MRI to CT image. However, there is no specific optimization of the network itself in previous MRI/CT translation works, resulting in mistakes in details such as the skull margin and cavity edge. These errors might have moderate effect on conventional radiotherapy, but for boron neutron capture therapy (BNCT), the skin dose will be a critical part of the dose composition. Thus, the purpose of this work is to create a self‐attention network that could directly transfer MRI to synthetical computerized tomography (sCT) images with lower inaccuracy at the skin edge and examine the viability of magnetic resonance (MR)‐guided BNCT. Methods: A retrospective analysis was undertaken on 104 patients with brain malignancies who had both CT and MRI as part of their radiation treatment plan. The CT images were deformably registered to the MRI. In the U‐shaped generation network, we introduced spatial and channel attention modules, as well as a versatile "Attentional ResBlock," which reduce the parameters while maintaining high performance. We employed five‐fold cross‐validation to test all patients, compared the proposed network to those used in earlier studies, and used Monte Carlo software to simulate the BNCT process for dosimetric evaluation in test set. Results: Compared with UNet, Pix2Pix, and ResNet, the mean absolute error (MAE) of self‐attention ResUNet (SARU) is reduced by 12.91, 17.48, and 9.50 HU, respectively. The "two one‐sided tests" show no significant difference in dose‐volume histogram (DVH) results. And for all tested cases, the average 2%/2 mm gamma index of UNet, ResNet, Pix2Pix, and SARU were 0.96 ± 0.03, 0.96 ± 0.03, 0.95 ± 0.03, and 0.98 ± 0.01, respectively. The error of skin dose from SARU is much less than the results from other methods. Conclusions: We have developed a residual U‐shape network with an attention mechanism to generate sCT images from MRI for BNCT treatment planning with lower MAE in six organs. There is no significant difference between the dose distribution calculated by sCT and real CT. This solution may greatly simplify the BNCT treatment planning process, lower the BNCT treatment dose, and minimize image feature mismatch. [ABSTRACT FROM AUTHOR]

A 'two-incision' approach for en bloc resection of periacetabular tumors and prosthesis reconstruction is described. The first incision begins in the middle of the iliac crest, continues over the inguinal ligament, extends to the symphysis pubis and then turns down to ischial tuberosity. The muscles attached to the iliac crest are only separated from its internal side. All the attachments of the abductor muscles to the iliac crest are left intact. The second incision runs from the sacroiliac joint to the greater trochanter and is curved in shape, providing external exposure of the sciatic notch and ischial tuberosity. Communication between the two approaches is possible inside and outside under the abductor muscles or through the sciatic notch. En bloc resection of the tumor is performed by cutting the pubic symphysis and iliac as planned preoperatively. The iliac osteotomy is performed by using a Gigli saw that has been led through the sciatic notch and under the abductor muscles. This 'two-incision' approach not only provides enough exposure to perform en bloc resection of periacetabular tumors, but also protects the continuity of the abductor muscles between the pelvis and greater trochanter, thus preventing prosthesis dislocation. [ABSTRACT FROM AUTHOR]

A simplified and appealing strategy via a chiral catalyst to facilitate the electrochemical process and provide asymmetric induction of radical reactions is particularly desirable and would have potential applications in electrosynthesis, organic chemistry, and drug discovery. Here, we introduced a novel electrolytic system that diverts the standard ionic reactivity to new catalytic functions, enabling mechanistically distinct single‐electron transfer‐based enantioselective routes to exhibit a brand‐new pattern of reactivity—electricity‐driven asymmetric catalysis as a privileged chiral platform for enantioselective radical allylation. The nickel‐catalyzed activation of nucleophiles triggered a single‐electron transfer process to provide a chiral catalyst‐bound radical cation intermediate, which could be applied as an alternative strategy for the development of stereocontrolled radical reactions. [ABSTRACT FROM AUTHOR]

A simplified and appealing strategy via a chiral catalyst to facilitate the electrochemical process and provide asymmetric induction of radical reactions is particularly desirable and would have potential applications in electrosynthesis, organic chemistry, and drug discovery. Here, we introduced a novel electrolytic system that diverts the standard ionic reactivity to new catalytic functions, enabling mechanistically distinct single‐electron transfer‐based enantioselective routes to exhibit a brand‐new pattern of reactivity—electricity‐driven asymmetric catalysis as a privileged chiral platform for enantioselective radical allylation. The nickel‐catalyzed activation of nucleophiles triggered a single‐electron transfer process to provide a chiral catalyst‐bound radical cation intermediate, which could be applied as an alternative strategy for the development of stereocontrolled radical reactions. [ABSTRACT FROM AUTHOR]

Peripheral nerve injury‐induced spinal microglial proliferation plays a pivotal role in neuropathic pain. So far, key intracellular druggable molecules involved in this process are not identified. The nuclear factor of activated T‐cells (NFAT1) is a master regulator of immune cell proliferation. Whether and how NFAT1 modulates spinal microglial proliferation during neuropathic pain remain unknown. Here it is reported that NFAT1 is persistently upregulated in microglia after spinal nerve ligation (SNL), which is regulated by TET2‐mediated DNA demethylation. Global or microglia‐specific deletion of Nfat1 attenuates SNL‐induced pain and decreases excitatory synaptic transmission of lamina II neurons. Furthermore, deletion of Nfat1 decreases microglial proliferation and the expression of multiple microglia‐related genes, such as cytokines, transmembrane signaling receptors, and transcription factors. Particularly, SNL increases the binding of NFAT1 with the promoter of Itgam, Tnf, Il‐1b, and c‐Myc in the spinal cord. Microglia‐specific overexpression of c‐MYC induces pain hypersensitivity and microglial proliferation. Finally, inhibiting NFAT1 and c‐MYC by intrathecal injection of inhibitor or siRNA alleviates SNL‐induced neuropathic pain. Collectively, NFAT1 is a hub transcription factor that regulates microglial proliferation via c‐MYC and guides the expression of the activated microglia genome. Thus, NFAT1 may be an effective target for treating neuropathic pain. [ABSTRACT FROM AUTHOR]

12‐Step program: The combined use of cinchona alkaloid based amine and chiral phosphoric acid enabled the asymmetric alkylation reaction of 3‐hydroxyoxindoles with aldehydes to give 3,3′‐disubstituted oxindoles in excellent enantioselectivities, which allows for the enantioselective total synthesis of (+)‐gliocladin C in 12 steps from 3‐hydroxyoxindole with 19 % overall yield (see scheme; PMB=para‐methoxybenzyl). [ABSTRACT FROM AUTHOR]

Abstract Chemokines are important mediators in immune responses and inflammatory processes of neuroimmunologic and infectious diseases. Although chemokines are expressed predominantly by cells of the immune system, neurons also express chemokines and chemokine receptors. We report herein that human neuronal cells (NT2-N) produce macrophage inflammatory protein-1α and -1β (MIP-1α and MIP-1β), which could be enhanced by interleukin (IL)-1β at both mRNA and protein levels. The addition of supernatants from human peripheral blood monocyte-derived macrophage (MDM) cultures induced MIP-1β mRNA expression in NT2-N cells. Anti-IL-1β antibody removed most, but not all, of the MDM culture supernatant-induced MIP-1β mRNA expression in NT2-N cells, suggesting that IL-1β in the MDM culture supernatants is a major factor in the induction of MIP-1β expression. Investigation of the mechanism(s) responsible for IL-1β-induced MIP-1α and -1β expression demonstrated that IL-1β activated nuclear factor kappa B (NF-κB) promoter-directed luciferase activity in NT2-N cells. Caffeic acid phenethyl ester, a potent and specific inhibitor of activation of NF-κB, not only blocked IL-1β-induced activation of the NF-κB promoter but also decreased IL-1β-induced MIP-1α and -1β expression in NT2-N cells. These data suggest that NF-κB is at least partially involved in the IL-1β-mediated action on MIP-1α and -1β in NT2-N cells. IL-1β-mediated up-regulation of β-chemokine expression may have important implications in the immunopathogenesis of inflammatory diseases in the CNS. [ABSTRACT FROM AUTHOR]

Reduced denatured lysozyme tends to aggregate at neutral pH and competition between productive folding and aggregation substantially reduces the efficiency of refolding. Trigger factor, a folding catalyst and chaperone can, depending on the concentration of trigger factor and the solution conditions, cause either a substantial increase (chaperone activity) or a substantial decrease (antichaperone activity) in the recovery of native lysozyme as compared with spontaneous refolding. When trigger factor is working as a chaperone, the reactivation rates of lysozyme are decelerated and aggregation decreases with increasing trigger factor concentrations. Under conditions where antichaperone activity of trigger factor dominates, the reactivation rates of lysozyme are accelerated and aggregation is increased. Trigger factor and lysozyme were both released from the aggregates on re-solubilization with urea indicating that trigger factor participates directly in aggregate formation and is incorporated into the aggregates. The apparently dual effect of trigger factor toward refolding of lysozyme is a consequence of the peptide binding ability and may be important in regulation of protein biosynthesis. [ABSTRACT FROM AUTHOR]

Presents a hypothesis for the origin of meiosis. Evolution of meiosis by blending features of two responses that cells have to deal with double-strand-DNA breaks, recombinational repair and apoptosis; Agreement of the hypothesis with molecule mechanisms, cytological phenomena and the fossil records.

Objectives: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease that affects the quality of life (QoL) of patients. This study aimed to evaluate the differences in perceptions of PBC among physicians from different hospital departments and patients with PBC. Methods: An online survey regarding the general knowledge, diagnosis, and management of PBC was completed by physicians and patients. Results: A total of 239 patients with PBC and 239 physicians from eight hospital departments (gastroenterology, infectious diseases, rheumatology, hepatobiliary surgery, pathology, clinical laboratory, ultrasound, and radiology) completed the survey. The results showed that physicians from departments other than gastroenterologists and rheumatologists lacked knowledge of PBC, and that junior gastroenterologists were uncertain about the diagnostic and treatment pathways of PBC. Importantly, the lack of knowledge significantly impacted the QoL of patients, especially the emotional scores of PBC‐40 (odds ratio −2.556, 95% confidence interval −3.852 to −1.260, P < 0.001). In addition, there was a perceived knowledge gap between patients and gastroenterologists. Conclusions: Physicians must improve their awareness of PBC. Patient education and patient–physician communication are important for improving the patient's QoL. [ABSTRACT FROM AUTHOR]

Tsukushi (TSK), a newly identified hepatokine, is a member of the small leucine‐rich proteoglycans (SLRPs) family. TSK was originally isolated and identified in the lens of the chicken. Preliminary research on TSK has focused on its role in various physiological processes such as growth and development, wound healing, and cartilage formation. In recent years, the role of TSK in regulating cell signaling pathways, cell proliferation, and differentiation has been studied. In addition, the research has gradually expanded to the fields of glycolipid metabolism and energy balance. This article briefly reviews the role of TSK in the physiological and pathological process. [ABSTRACT FROM AUTHOR]

The field of electrochemical synthesis has developed rapidly over the last decade and has provided alternative synthetic methods with the absence of stoichiometric amounts of chemical oxidants or reductants. Although sustainable electrosynthetic procedures have been developed, relatively few examples of highly enantioselective catalytic electrosynthesis have been reported to date. The development of general strategies for electrochemical enantiocontrol has thus proven to be a considerable challenge. This Minireview highlights the current knowledge and recent advances in the synthetic utility of electrochemical transformations for asymmetric synthesis. Specifically, three major types of catalytic enantioselective strategy in electrosynthesis are outlined, including electrochemical activation of chiral catalyst‐bound substrates, asymmetric cascade electrochemical processes, and chemically modified chiral electrodes. [ABSTRACT FROM AUTHOR]

Background: Boron neutron capture therapy (BNCT) is a binary radiotherapy based on the 10B(n, α)7Li capture reaction. Nonradioactive isotope 10B atoms which selectively concentrated in tumor cells will react with low energy neutrons (mainly thermal neutrons) to produce secondary particles with high linear energy transfer, thus depositing dose in tumor cells. In clinical practice, an appropriate treatment plan needs to be set on the basis of the treatment planning system (TPS). Existing BNCT TPSs usually use the Monte Carlo method to determine the three‐dimensional (3D) therapeutic dose distribution, which often requires a lot of calculation time due to the complexity of simulating neutron transportation. Purpose: A neural network‐based BNCT dose prediction method is proposed to achieve the rapid and accurate acquisition of BNCT 3D therapeutic dose distribution for patients with glioblastoma to solve the time‐consuming problem of BNCT dose calculation in clinic. Methods: The clinical data of 122 patients with glioblastoma are collected. Eighteen patients are used as a test set, and the rest are used as a training set. The 3D‐UNET is constructed through the design optimization of input and output data sets based on radiation field information and patient CT information to enable the prediction of 3D dose distribution of BNCT. Results: The average mean absolute error of the predicted and simulated equivalent doses of each organ are all less than 1 Gy. For the dose to 95% of the GTV volume (D95), the relative deviation between predicted and simulated results are all less than 2%. The average 2 mm/2% gamma index is 89.67%, and the average 3 mm/3% gamma index is 96.78%. The calculation takes about 6 h to simulate the 3D therapeutic dose distribution of a patient with glioblastoma by Monte Carlo method using Intel Xeon E5‐2699 v4, whereas the time required by the method proposed in this study is almost less than 1 s using a Titan‐V graphics card. Conclusions: This study proposes a 3D dose prediction method based on 3D‐UNET architecture in BNCT, and the feasibility of this method is demonstrated. Results indicate that the method can remarkably reduce the time required for calculation and ensure the accuracy of the predicted 3D therapeutic dose‐effect. This work is expected to promote the clinical development of BNCT in the future. [ABSTRACT FROM AUTHOR]

Background & Aims: Nonalcoholic steatohepatitis (NASH), a more severe subtype of nonalcoholic fatty liver disease, can cause cirrhosis and hepatocellular carcinoma. Macrophages play critical roles in initiating and maintaining NASH‐induced liver inflammation and fibrosis. However, the underlying molecular mechanism of macrophage chaperone‐mediated autophagy (CMA) in NASH remains unclear. We aimed to investigate the effects of macrophage‐specific CMA on liver inflammation and identify a potential therapeutic target for NASH treatment. Methods: The CMA function of liver macrophages was detected using Western blot, quantitative reverse transcription‐polymerase chain reaction (RT‐qPCR) and flow cytometry. By constructing myeloid‐specific CMA deficiency mice, we evaluated the effects of deficient CMA of macrophages on monocyte recruitment, liver injury, steatosis and fibrosis in NASH mice. A label‐free mass spectrometry was utilized to screen the substrates of CMA in macrophages and their mutual interactions. The association between CMA and its substrate was further examined by immunoprecipitation, Western blot and RT‐qPCR. Results: A typical hallmark in murine NASH models was impaired CMA function in hepatic macrophages. Monocyte‐derived macrophages (MDM) were the dominant macrophage population in NASH, and CMA function was impaired in MDM. CMA dysfunction aggravated liver‐targeted recruitment of monocyte and promoted steatosis and fibrosis. Mechanistically, Nup85 functions as a substrate for CMA and its degradation was inhibited in CMA‐deficient macrophages. Inhibition of Nup85 attenuated the steatosis and monocyte recruitment caused by CMA deficiency in NASH mice. Conclusions: We proposed that the impaired CMA‐induced Nup85 degradation aggravated monocyte recruitment, promoting liver inflammation and disease progression of NASH. [ABSTRACT FROM AUTHOR]

The regioselective title reaction between vinyl benzoxazinanones and aryl, alkenyl or alkyl substituted enals delivers benzazepine derivatives in high yields, with high diastereo- and excellent enantioselectivities. [ABSTRACT FROM AUTHOR]

Abstract: Semiconducting single‐walled carbon nanotubes (sc‐SWCNTs) enriched by a conjugated polymer extraction process have been actively studied for various applications in both electronics and optoelectronics. Although the resulting tube samples usually have high sc‐purity and concentration, SWCNT networks from such dispersions typically contain residual conjugated polymer that may degrade device performance and its removal remains a challenge while maintaining uniform, dense SWCNT thin film networks. In this study, a novel polymer–SWCNT combination based on an alternating bisfuran‐s‐tetrazine and benzo[1,2‐b:4,5‐b′]dithiophene copolymer abbreviated as PBDTFTz is proposed. This polymer decomposes at >250 °C or under UV irradiation. In situ transistor characterization under laser irradiation confirms the polymer decomposition. The study of the tube network in the transistor channel at various channel lengths reveals significantly reduced contact resistance attributed to removal of the wrapping PBDTFTz polymer. In ammonia sensing experiments, sc‐SWCNT networks demonstrate rapid and reversible responses, while the unwrapped nanotube networks prove superior in terms of signal to noise ratio and a detection limit of 2.5 ppb is calculated, almost four times better than polymer wrapped nanotubes. [ABSTRACT FROM AUTHOR]

A hybrid model based on the positive matrix factorization (PMF) model and the health risk assessment model for assessing risks associated with sources of perfluoroalkyl substances (PFASs) in water was established and applied at Dianchi Lake to test its applicability. The new method contains 2 stages: 1) the sources of PFASs were apportioned by the PMF model and 2) the contribution of health risks from each source was calculated by the new hybrid model. Two factors were extracted by PMF, with factor 1 identified as aqueous fire-fighting foams source and factor 2 as fluoropolymer manufacturing and processing and perfluorooctanoic acid production source. The health risk of PFASs in the water assessed by the health risk assessment model was 9.54 × 10−7 a−1 on average, showing no obvious adverse effects to human health. The 2 sources' risks estimated by the new hybrid model ranged from 2.95 × 10−10 to 6.60 × 10−6 a−1 and from 1.64 × 10−7 to 1.62 × 10−6 a−1, respectively. The new hybrid model can provide useful information on the health risks of PFAS sources, which is helpful for pollution control and environmental management. Environ Toxicol Chem 2018;37:107-115. © 2017 SETAC [ABSTRACT FROM AUTHOR]

A novel N-heterocyclic carbene-catalyzed regiodivergent annulation reaction of N-iminoisoquinolinium ylides with enals is studied. [ABSTRACT FROM AUTHOR]

Various 1,2-diazepine derivatives are synthesized by regio- and enantioselective formal [4 + 3] annulation reaction between enals and in situ formed azoalkenes. [ABSTRACT FROM AUTHOR]

The process is applied to various azaaurones and α,β-unsaturated aldehydes to afford indole-based spiro compounds with a quaternary stereogenic center. [ABSTRACT FROM AUTHOR]

The article presents the chemical steps involved in the biomimetic asymmetric 1,3-dipolar cycloaddition.

Objective: To compare the surgical outcomes of debridement, antibiotics, and single‐stage total hip replacement (DASR) vs two‐stage arthroplasty (two‐stage arthroplasty) for chronic destructive septic hip arthritis (SHA). Methods: Cases of chronic destructive SHA treated by DASR or two‐stage arthroplasty in our department from January 2008 to October 2021 were retrospectively reviewed. Patient demographic information, perioperative inflammation markers, intraoperative blood loss, microbial culture, and metagenomic new generation sequencing results were recorded. The perioperative complications, hospital stay, hospitalization cost, infection recurrence rate, and Harris Hip Score (HHS) at the last follow‐up were compared between the two groups. Results: A total of 28 patients were included in the study, including 11 patients who received DASR and 17 patients who received two‐stage arthroplasty. There was no significant difference in demographic information, preoperative serum inflammatory markers, synovial fluid white blood cell count, or percentage of polymorphonuclear leukocytes between the two groups. The DASR group demonstrated significantly lower intraoperative blood loss [(368.2 ± 253.3) mL vs (638.2 ± 170.0) mL, p = 0.002], hospital stay [(22.6 ± 8.1) days vs (43.5 ± 13.2) days, p < 0.0001], and hospitalization expenses [(81,269 ± 11,496) RMB vs (137,524 ± 25,516) RMB, p < 0.0001] than the two‐stage arthroplasty group. In the DASR group, one patient had dislocation as a complication. There were no cases with recurrence of infection. In the two‐stage arthroplasty group, there was one case complicated with spacer fracture, one case with spacer dislocation, and one case with deep vein thrombosis of the lower limbs. There were no cases with recurrence of infection. There were no significant differences in the readmission rate, complication rate, or HHS at the last follow‐up between the two groups. Conclusions: Both DASR and two‐stage arthroplasty achieved a satisfactory infection cure rate and functional recovery for chronic destructive SHA, and DASR demonstrated significantly lower intraoperative blood loss, hospital stay, and hospitalization costs than two‐stage arthroplasty. For appropriately indicated patients, if microbial data are available and a standardized debridement protocol is strictly followed, DASR can be a treatment option. [ABSTRACT FROM AUTHOR]

This method uses a chiral primary amine and a chiral phosphoric acid as an organocatalytic system to yield the products (III) with high enantioselectivities. [ABSTRACT FROM AUTHOR]

The title reaction of 3,3′-bisindolin-2-ones with vinylcarbamates catalyzed by a chiral phosphoric acid affords the corresponding indolinones with concomitant generation of an all-carbon quaternary stereogenic center in high yield and excellent enantioselectivity. [ABSTRACT FROM AUTHOR]