Gate tunable spatial accumulation of valley-spin in chemical vapor deposition grown 40°-twisted bilayer WS2

The emerging two-dimensional materials,particularly transition metal dichalcogenides(TMDs),are known to exhibit valley degree of freedom with long valley lifetime,which hold great promises in the implementation of valleytronic devices.Especially,light-valley interactions have attracted attentions in these systems,as the electrical generation of valley magnetization can be readily achieved—a rather different route toward magnetoelectric(ME)effect as compared to that from conventional electron spins.However,so far,the moiré patterns constructed with twisted bilayer TMDs remain largely unexplored in regard of their valley spin polarizations,even though the symmetry might be distinct from the AB stacked bilayer TMDs.Here,we study the valley Hall effect(VHE)in 40°-twisted chemical vapor deposition(CVD)grown WS2moiré transistors,using optical Kerr rotation measurements at 20 K.We observe a clear gate tunable spatial distribution of the valley carrier imbalance induced by the VHE when a current is exerted in the system.

Unsaturated bi-heterometal clusters in metal-vacancy sites of 2D MoS2 for efficient hydrogen evolution

The valence states and coordination structures of doped heterometal atoms in two-dimensional(2D)nanomaterials lack predictable regulation strategies.Hence,a robust method is proposed to form unsaturated heteroatom clusters via the metal-vacancy restraint mechanism,which can precisely regulate the bonding and valence state of heterometal atoms doped in 2D molybdenum disulfide.The unsaturated valence state of heterometal Pt and Ru cluster atoms form a spatial coordination structure with Pt–S and Ru–O–S as catalytically active sites.Among them,the strong binding energy of negatively charged suspended S and O sites for H+,as well as the weak adsorption of positively charged unsaturated heterometal atoms for H*,reduces the energy barrier of the hydrogen evolution reaction proved by theoretical calculation.Whereupon,the electrocatalytic hydrogen evolution performance is markedly improved by the ensemble effect of unsaturated heterometal atoms and highlighted with an overpotential of 84 mV and Tafel slope of 68.5 mV dec^(−1).In brief,this metal vacancy-induced valence state regulation of heterometal can manipulate the coordination structure and catalytic activity of heterometal atoms doped in the 2D atomic lattice but not limited to 2D nanomaterials.

Growth of large-scale two-dimensional insulator Na2Ta4O11 through chemical vapor deposition

The insulator Na2Ta4O11 has been considered as a potential photocatalyst.However,little attention has been given to the synthesis of Na2Ta4O11 nanoparticles,let alone the growth of two-dimensional(2D)layered Na2Ta4O11 flake,which may bring innovative properties and promising applications.Here,the 2D thin-layer Na2Ta4O11 flake was first produced by chemical vapor deposition(CVD)method,with the smallest thickness reported currently.We have also synthesized 2D Na2Ta4O11 flake over 100μm,which was the largest value over the 2D level reported to date.Our work proposed novel strategies to synthesize other 2D metal oxide material and endow the Na2Ta4O11 more properties and applications.

Synthesis, SAR, and in Silico ADME Screening Studies of Some 9-Amino-3-Phenylacridone Derivatives as Topoisomerase II Inhibitors

Cancer is a leading cause of death globally, claiming about 9.6 million lives and approximately 420 million new cases of cancer will be diagnosed in the world by the year 2025. The aim of this study was to synthesize and computationally evaluate pharmacological potential of some derivatives of 9-amino-3-phenylacridone, as topoisomerase II (Topo II) inhibitors. In this study, 10 derivatives of 3-phenyl-9-aminoacridone were chemically synthesized and characterized, and the potential pharmacological indications of these compounds were computationally predicted by methods such as ADMET prediction, molecular target prediction and molecular docking. The results showed that two derivatives (58e and 58j) were non-permeant of blood-brain barrier, and this property was found similar to that of amsacrine and etoposide. The results of molecular docking of the ten derivatives of 3-phenyl-9-aminoacridone that were synthesized in this work showed that the synthetic compounds (58a-j) and the standard drugs have overall best binding affinities for human acetylcholine esterase than butyrylcholinesterase, and overall best binding affinities for human topo IIα than human topo IIβ. Overall, the results of this study suggest that the synthetic compounds 58a, 58c, 58f, 58g, and 58i could probably inhibit topo IIα by catalytic inhibition as seen with amsacrine, but only 58b and 58e possessed DNA non-intercalation properties as seen with etoposide, serving as topo II poison. In conclusion, this study showed that 3-phenyl-9-aminoacridone derivatives are potential inhibitor of topo IIα/β both by catalytic inhibition and poison as non-intercalator of DNA.

Gilbert's syndrome: High frequency of the (TA)_7 TAA allele in India and its interaction with a novel CAT insertion in promoter of the gene for bilirubin UDP-glucuronosyltransferase 1 gene

瞄准：在吉伯的症候群(GS ) 在 UDP-glucuronosyltransferase 1 (UGT1A1 ) 基因识别变体并且在印度在正常控制之中在 TA 插入和它的影响的印度，以及频率为 TA 插入和 GS 估计在纯合性之间的协会。方法：95 个 GS 盒子和 95 正常控制被选择。肝工作，另外的测试被做。倡导者和 UGT1A1 基因的所有 5 前 ons 被重新定序。对新奇 trinucleotide 插入的功能的评价被做由在 silico 分析并且由估计 UGT1A1，倡导者活动在 Hep G2 由适当构造的酶记者试金执行了房间线。结果：在 GS 病人之中， 80% 为 TA 插入是同型结合的，它比从另外的种族组的报告高好几倍。吝啬的 UCB 水平与仅仅这插入的一个拷贝在个人之中被提高，它不与有二个拷贝的那些显著地不同。在 UGT1A1 基因的许多新 DNA 变体被发现，包括在倡导者的插入在 GS 病人的一个子集(10%) 发现了的 trinucleotide (猫) ，然而并非在正常之中控制。In-silico 分析证明在倡导者和功能的分析的合拢 DNA 的显著变化在 UGT1A1 基因源于这插入的抄写效率显示出 20 褶层减小，显著地从而提高 UCB 水平。结论：GS 的基因传染病学越过种族组是可变的，在 UGT1A1 倡导者变体之中的上位相互作用调制胆红素 glucuronidation。

Niclosamide,an old antihelminthic agent,demonstrates antitumor activity by blocking multiple signaling pathways of cancer stem cells

Niclosamide,an oral antihelminthic drug,has been used to treat tapeworm infection for about 50 years.Niclosamide is also used as a molluscicide for water treatment in schistosomiasis control programs.Recently,several groups have independently discovered that niclosamide is also active against cancer cells,but its precise mechanism of antitumor action is not fully understood.Evidence supports that niclosamide targets multiple signaling pathways (NF-κB,Wnt/β-catenin,Notch,ROS,mTORC1,and Stat3),most of which are closely involved with cancer stem cells.The exciting advances in elucidating the antitumor activity and the molecular targets of this drug will be discussed.A method for synthesizing a phosphate pro-drug of niclosamide is provided.Given its potential antitumor activity,clinical trials for niclosamide and its derivatives are warranted for cancer treatment.

Matrix metalloproteinases and gastrointestinal cancers: Impacts of dietary antioxidants

The process of carcinogenesis is tightly regulated by antioxidant enzymes and matrix degrading enzymes, namely, matrix metalloproteinases(MMPs). Degradation of extracellular matrix(ECM) proteins like collagen, proteoglycan, laminin, elastin and fibronectin is considered to be the prerequisite for tumor invasion and metastasis. MMPs can degrade essentially all of the ECM components and, most MMPs also substantially contribute to angiogenesis, differentiation, proliferation and apoptosis. Hence, MMPs are important regulators of tumor growth both at the primary site and in distant metastases; thus the enzymes are considered as important targets for cancer therapy. The implications of MMPs in cancers are no longer mysterious; however, the mechanism of action is yet to be explained. Herein, our major interest is to clarify how MMPs are tied up with gastrointestinal cancers. Gastrointestinal cancer is a variety of cancer types, including the cancers of gastrointestinal tract and organs, i.e., esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus. The activity of MMPs is regulated by its endogenous inhibitor tissue inhibitor of metallopro-teinase(TIMP) which bind MMPs with a 1:1 stoichiometry. In addition, RECK(reversion including cysteinerich protein with kazal motifs) is a membrane bound glycoprotein that inhibits MMP-2,-9 and-14. Moreover, α2-macroglobulin mediates the uptake of several MMPs thereby inhibit their activity. Cancerous conditions increase intrinsic reactive oxygen species(ROS) through mitochondrial dysfunction leading to altered protease/anti-protease balance. ROS, an index of oxidative stress is also involved in tumorigenesis by activation of different MAP kinase pathways including MMP induction. Oxidative stress is involved in cancer by changing the activity and expression of regulatory proteins especially MMPs. Epidemiological studies have shown that high intake of fruits that rich in antioxidants is associated with a lower cancer incidence. Evidence indicates that some antioxidants inhibit the growth of malignant cells by inducing apoptosis and inhibiting the activity of MMPs. This review is discussed in six subchapters, as follows.

In vitro assessment of gastrointestinal viability of two photosynthetic bacteria,Rhodopseudomonas palustris and Rhodobacter sphaeroides

The objectives of this study were to assess the potential of two photosynthetic bacteria (PSB), Rhodopseudomonas palustris HZ0301 and Rhodobacter sphaeroides HZ0302, as probiotics in aquaculture. The viability of HZ0301 and HZ0302 in simulated gastric transit conditions (pH 2.0, pH 3.0 and pH 4.0 gastric juices) and in simulated small intestinal transit conditions (pH 8.0, with or without 0.3% bile salts) was tested. The effects of HZ0301 and HZ0302 on the viability and permeability of intestinal epithelial cell in primary culture of tilapias, Oreochromis nilotica, were also detected. All the treatments were deter-mined with three replicates. The simulated gastric transit tolerance of HZ0301 and HZ0302 strains was pH-dependent and cor-respondingly showed lower viability at pH 2.0 after 180 min compared with pH 3.0 and pH 4.0. Both HZ0301 and HZ0302 were tolerant to simulated small intestine transit with or without bile salts in our research. Moreover, there was no significant difference (P>0.05) among three treatments including the control and the groups treated with HZ0301 or HZ0302 both in intestinal epithelial cell viability and membrane permeability, showing no cell damage. In summary, this study demonstrated that HZ0301 and HZ0302 had high capacity of upper gastrointestinal transit tolerance and were relatively safe for intestinal epithelial cells of tilapias.

Distribution of hepatitis B virus genotypes:Phylogenetic analysis and virological characteristics of Genotype C circulating among HBV carriers in Kolkata,Eastern India

AIM: To evaluate the genotype distribution of hepatitis B virus (HBV) in Eastern India and to clarify the phyloge- netic origin and virological characteristics of the recently identifi ed genotype C in this region. METHODS: Genotype determination, T1762/A1764 mutation in the basal core promoter (BCP) and A1896 mutation in the precore region of 230 subjects were de- termined by restriction fragment length polymorphism method (RFLP) and the result was confi rmed by direct sequencing. RESULTS: The predominant genotypes D (HBV/D) and A (HBV/A) were detected in 131/230 (57%) and 57/230 (25%) samples. In addition, genotype C (HBV/C) was detected in 42/230 (18%) isolates. Surface gene region was sequenced from 45 isolates (27 HBV/C, 9 HBV/A and 9 HBV/D). Phylogenetic analysis revealed that all of the HBV/C sequences clustered with South East Asian subgenotype (HBV/Cs). The sequence data showed re- markable similarity with a Thai strain (AF068756) (99.5% ± 0.4% nucleotide identities) in 90% of the genotype C strains analyzed. T1762/A1764 mutation in BCP re- gion, associated with high ALT was signifi cantly higher in HBeAg negative isolates than HBeAg positive isolates. Frequency of A1896 mutation leading to HBeAg negativ- ity was low.CONCLUSION: The present study reports the genotypic distribution and the characteristics of partial genome sequences of HBV/C isolates from Eastern India. Low genetic diversity and confi nement of HBV/C in Eastern India possibly indicate a recent, limited, spread in this region. Genotype C with T1762/A1764 mutation has been reported to increase the risk for hepatocellular car- cinoma; therefore genotype C carriers in Eastern India should be carefully monitored.

Structure and diversity dynamics of microbial communities at day and night:investigation of meromictic Lake Doroninskoe,Transbaikalia,Russia

Extreme environmental conditions are key factors in the formation of the structure and diversity of microbial communities. In meromictic ecosystems, extreme conditions and a stable stratification of physical, chemical and biological parameters lead to diversity and heterogeneity of microenvironments. Lake Doroninskoe is located in an extreme geographical area and diff ers from other known meromictic reservoirs of the world by a low level of illumination in the chemocline and a rare type of alkaline water in sedimentary rocks formed by evaporative concentration. To understand the key factors that shape the composition and structure of the microbial community, the macro-and micro-variations in space and time are of great importance. We investigated the short-term dynamics of the structure and diversity of microbial communities of the meromictic soda lake, Lake Doroninskoe, at day and night using highthroughput sequencing and bioinformatics. Metagenomic analysis of 16 S rRNA gene amplicons showed that the microbial communities had a high taxonomic diversity both at day and night. Sixteen bacterial and three archaeal phyla were identified. Proteobacteria were dominant and comprised 75% during the day, increasing to 90% at night. Metabolically stable denitrifying bacteria that were able to use a variety of alternative electron acceptors and electron donors were prevalent in Lake Doroninskoe. They belonged to the families Enterobacteriaceae(class Gammaproteobacteria) and Alcaligenaceae(class Betaproteobacteria). Statistically significant differences between day and night microbial communities were found. During the day, the microbial community was the most diverse. We discuss the peculiarities of the underexplored shortterm dynamics of the structure and diversity of the microbial communities of the meromictic soda Lake Doroninskoe, and propose topics for prospective studies.

Interface Effect of Ru-MoS_(2) Nanoflowers on Lignin Substrate for Enhanced Hydrogen Evolution Activity

The catalytic performance of Molybdenum disulfide(MoS_(2)) has been still far from that of Pt-based catalysts for inadequate active sites and sluggish electron transfer kinetics. Through engineering the interface between MoS_(2)-based materials and supported substrates, hybrid Ru-doped MoS_(2) on carbonized lignin(CL) is designed and prepared as efficient catalyst for hydrogen evolution reaction(HER). The CL substrate not only facilitates the growth of MoS_(2) nanoflowers, but also promotes the electron transfer. Ru doping increases active sites greatly for HER. The hybrid catalyst achieves a low onset overpotential of 25 mV and a low Tafel slope of 46 m V dec^(-1). The favorable HER activity ascribes to the interfacial interaction between MoS_(2) and CL. Density functional theory calculations further confirm the improved HER performance with doped Ru atoms. This study presents a prototype application to design electrocatalysts with enhanced carrier mobility and high-density active sites based on interface effect.

Evaluation of Benzamide Derivatives as New Influenza A Nucleoprotein Inhibitors

Virus nucleoprotein (NP) is an emerging target for drug development for Influenza. We designed benzamide derivatives as new inhibitors of NP that demonstrate good potency in blocking influenza A. Screening revealed that compound 39 was the most potent molecule in the series, exhibiting IC50 values of 0.46 and 0.27 μM in blocking the replication of H3N2 (A/HK/8/68) and (A/WSN/33) influenza A viral strains. The observed inhibition of viral replication correlated well with cytopathic protection. Furthermore, based on computational analysis and fluorescence microscopy, it was determined that compound 39 inhibited nuclear accumulation by targeting influenza A viral nucleoproteins. Finally, the rodent pharmacokinetic profile of compound 32 displayed half-life of greater than 4 hours and bioavailability greater than 20%, suggesting this class of molecules had drug-like properties.

Basic Study Hepatitis B virus detected in paper currencies in a densely populated city of India: A plausible source of horizontal transmission?

BACKGROUND The recent rise in the incidence of hepatitis B virus(HBV)infections in a densely populated city of eastern India(“mixing vessel”of people of varied socioeconomic and immune status)prompted this study.Applying saliva on fingers for enumerating bank notes is a common practice in the Indian subcontinent.Paper notes may be a potential source of“horizontal”transmission of this virus,especially if there are cuts/bruises on the oral mucous membrane or skin.AIM To investigate whether paper currencies could be a plausible mode of horizontal transmission of HBV infection.METHODS Polymerase chain reactions(PCR)followed by nucleotide sequencing was done for the detection of HBV.Hepatitis B virus surface antigen enzyme-linked immunosorbent assay(HBsAg ELISA)was performed on all HBV deoxyribonucleic acid-positive samples to check the detectability of the virus.Atomic force microscopy(AFM)was carried out for visual confirmation of HBV particles in ultracentrifuged/immunoprecipitated samples from currency paper washings.RESULTS HBV-specific PCRs on pellets obtained after ultracentrifugation/immunoprecipitation of the currency paper washings detected potentially intact/viable HBV(genotype D2)in 7.14%of samples(n=70).AFM gave the visual confirmation of HBV particles in ultracentrifuged/immunoprecipitated samples from currency paper washings.However,HBV isolates from the currency notes could not be detected by HBsAg ELISA.CONCLUSION It is a common practice in the Indian subcontinent to count paper currencies by applying saliva on fingertips.Paper notes may be a potential source of“horizontal”transmission of this virus,especially if there are cuts/bruises on the oral mucous membrane or skin,but it was practically not possible to demonstrate experimentally such transmission.Detection of potentially intact/viable and“occult”HBV from currency poses potential risk of silent transmission of this virus among the general population.

An automated multiwell plate reading flim microscope for live cell autofluorescence lifetime assays

Fluorescence lifetime imaging(FLIM)is increasingly used to read out cellular autofluorescenceoriginating from the coenzyme NADH in the context of investigating cell metabolic state.Wepresent here an automated multiwell plate reading FLIM microscope optimized for UV illumi-nation with the goal of extending high content fluorescence lifetime asays to readouts ofmetabolism,We demonstrate its application to automated cellular autofluorescence lifetime imaging and discuss the key practical issues associated with its implementation.In particular,weillustrate its capability to read out the NADH-lifetime response of cells to metabolic modulators,thereby illustrating the potential of the instrument for cytotoxicity studies,assays for drugdiscovery and stratified medicine.

Acquisition and dissemination mechanisms of CTXΦ in Vibrio cholerae : New paradigm for dif residents

Vibrio cholerae(V. cholerae) genome is equipped with a number of integrative mobile genetic element(IMGE) like prophages, plasmids, transposons or genomic islands, which provides fitness factors that help the pathogen to survive in changing environmental conditions. Metagenomic analyses of clinical and environmental V. cholerae isolates revealed that dimer resolution sites(dif) harbor several structurally and functionally distinct IMGEs. All IMGEs present in the dif region exploit chromosomally encoded tyrosine recombinases, Xer C and Xer D, for integration. Integration takes place due to site-specific recombination between two specific DNA sequences; chromosomal sequence is called att B and IMGEs sequence is called att P. Different IMGEs present in the att P region have different attP structure but all of them are recognized by Xer C and Xer D enzymes and mediate either reversible or irreversible integration. Cholera toxin phage(CTXΦ), a lysogenic filamentous phage carrying the cholera toxin genes ctx AB, deserves special attention because it provides V. cholerae the crucial toxin and is always present in the dif region of all epidemic cholera isolates. Therefore, understanding the mechanisms of integration and dissemination of CTXΦ, genetic and ecological factors which support CTXΦ integration as well as production of virion from chromosomally integrated phage genome and interactions of CTXΦ with other genetic elements present in the genomes of V. cholerae is important for learning more about the biology of cholera pathogen.

Reduction of serotonergic gene expression in the raphe nuclei of the midbrain under positive fighting experience in male mice

The concept of a major inhibitory role of serotonin in aggressive behavior is widely accepted by investigators. There was ample evidence that a pharmacologically-induced increase in the serotonin activity attenuates agonistic behavior in animals, and that the manipulations inhibiting the brain serotonergic system can elicit aggressiveness in male mice and rats. Repeated experience of aggression in daily agonistic interactions has been shown to reduce serotonin activity in brain of victorious male mice. The study aimed to analyze expression of the serotonergic genes -Tph2, Sert, Maoa and Htr1a, as well as the Bdnf and Creb genes in the midbrain raphe nuclei of male mice with positive fighting experience in daily encounters and male mice with the same track record of aggression followed by two-week no-fight period. It has been shown that mRNA levels of the serotonergic and Creb genes are reduced in the winners in comparison with male mice without consecutive positive fighting experience of aggression. After the fighting deprivation the Tph2, Sert, Bdnf and Creb genes recover their expression while mRNA levels of the Maoa and Htr1a genes proceed at a significantly higher level as compared with the respective controls. Downregulation of serotonergic genes is indicative of the inhibition of serotonergic activity under repeated experience of aggression. Nevertheless recovering of Tph2 and Sert gene expression and overexpression of the Maoa and Htr1a genes after no-fight period suggest that changes in brain serotonergic activity are not main cause of the behavioral pathology developing in male mice in this experimental context.

Author affiliation addition:“Hepatitis B virus detected in paper currencies in a densely populated city of India:A plausible source of horizontal transmission?”

Addition of authors’affiliation to"Hepatitis B virus detected in paper currencies in a densely populated city of India:A plausible source of horizontal transmission?"World J Hepatol 2020 Oct 27;12(10):775-791.In this article,one of the affiliations of two authors was not mentioned.Ruchi Supekar,a joint first author and Subhajit Biswas,the corresponding author are affiliated to Academy of Scientific and Innovative Research(AcSIR)Ghaziabad-201002,India.

Anti-Osteoporosis and Anti-Osteoarthritis Activity of Fresh Water Snail <i>(Viviparous bengalensis)</i>Flesh Extract in Experimental Animal Model

Aims: Aim was to evaluate the anti-osteoporotic and anti-osteoarthritic activity of fresh water snail (Viviparous bengalensis) (VB) flesh extract (VBE) in experimental model. Settings and Design: Experimental osteoporosis (OSP) was developed in female Wistar rats by bilateral overectomy and Osteoarthritis (OA) was developed in male Wistar rats by bacterial collagenase injection. Methods and Material: VB was collected locally and authenticated, then homogenized in 3500 rpm × 15 mins and supernatant was collected. Rats were divided into-Group-1: Sham control, Group-2: OSP/OA control, Group-3: Standard (vitD3 200 mg·kg -1;p.o., calcium i.p. 1500 mg·kg -1?× 15 days in OSP and indomethacin 0.25 mg·kg-1, p.o. × 5 alternative days in OA), Group-4: VBE treated (1 gm·kg-1;p.o. × 15 days), Group-5: VBE treated (2 mg·kg-1;p.o. × 15 days). Anti-osteoporotic and anti-osteoarthritic activity of VBE was examined through physical, urinary and serum parameters. Statistical use: Data were expressed in terms of mean ± SEM (n = 6). ANOVA was performed, p Key findings: It was observed that the body weight, ankle/ knee diameters, urinary markers hydroxyproline/glucosamine/calcium/phosphate/creatinine, serum ACP/ALP/TRAP, calcium/creatinine, cytokines (TNF-α/IL-1β/CINC-1) levels were changed significantly and restored after VBE treatment. Significance: Fresh water snail flesh extract possess anti-osteoporosis and anti-osteoarthritic activity in experimental animal models.

Analytical consideration of the selectivity of oligonucleotide hybridization

Systematic analysis of factors determining efficiency in discrimination of a point substitution (SNP) within specific DNA sequences was carried out in the context of hybridization approach. There are two types of selectivity that are critical for the rational design of highly specific oligonucleotides probes. The first type is the real selectivity of hybridization (fa) that is the ratio of association degrees of targets with an oligonucleotide probe upon the perfect and imperfect complex formation. This type of selectivity reflects the level of discrimination between matched and mismatched signals, which is determined both by experimental conditions and the thermodynamics of oligonucleotide hybridization. The second parameter characterizing the efficiency of SNP discrimination is the limit selectivity of hybridization, which determines the utmost value of fa at a given temperature. This value can be calculated as the ratio of corresponding equilibrium association constants of perfect and imperfect complex formation determined purely by thermodynamics. We have shown that the fa function is the most reliable characteristic describing the hybridization selectivity. For the analytical system designed to reveal any type of perturbation in DNA (e.g. SNP or modification), there is usually a temperature at which fa has its maximum value. The dependency of the fa maximum on different experimental parameters as well as the structural characteristics of a probe are described in details. The results allowed us to postulate points of principle to rationally design the most selective probes on the basis of oli- gonucleotides or their derivatives.