Postoperative chemotherapy with S-1 plus oxaliplatin versus S-1alone in locally advanced gastric cancer(RESCUE-GC study): a protocol for a phase Ⅲ randomized controlled trial

Background： The ACTS-GC study had shown postoperative adiuvant therapy with S-1 improved survival of patients with locally advanced gastric cancer. Addition of oxaliplatin to S-1 is considered to be acceptable as one of the treatment options for gastric cancer patients after radical gastrectomy with D2 lymph node excision. Methods： We have commenced a randomized phase III trial in December 2016 to evaluate S-I plus oxaliplatin compared with S-1 alone in the adjuvant setting for locally advanced gastric cancer. A total of 564 patients will be accrued from 13 Chinese institutions in two years. The primary endpoint is 3-year relapse-free survival. The secondary endpoints are 5-year overall survival, proportion of patients who complete the postoperative chemotherapy and incidence of adverse events. Ethic and dissemination： The trial has been approved by the institutional review board of each participating institution and it was activated on December, 2016. The enrollment will be finished in December, 2018. Patient＇s follow-up will be ended until December, 2023. Trial registration： ClinicalTrials.gov, identifier： NCT02867839. Registered on August 4, 2016.

The haplotype-resolved T2T reference genome highlights structural variation underlying agronomic traits of melon

Melon(Cucumis melo L.)is an important vegetable crop that has an extensive history of cultivation.However,the genome of wild and semi-wild melon types that can be used for the analysis of agronomic traits is not yet available.Here we report a chromosome-level T2T genome assembly for 821(C.melo ssp.agrestis var.acidulus),a semi-wild melon with two haplotypes of∼373 Mb and∼364 Mb,respectively.Comparative genome analysis discovered a significant number of structural variants(SVs)between melo(C.melo ssp.melo)and agrestis(C.melo ssp.agrestis)genomes,including a copy number variation located in the ToLCNDV resistance locus on chromosome 11.Genome-wide association studies detected a significant signal associated with climacteric ripening and identified one candidate gene CM_ac12g14720.1(CmABA2),encoding a cytoplasmic short chain dehydrogenase/reductase,which controls the biosynthesis of abscisic acid.This study provides valuable genetic resources for future research on melon breeding.

An Arthrobacter strain isolated from desert soils in the region of Shule River (China) can convert cellulose to potential biofuels

In this study, an Arthrobacter strain from desert soils in the Shule River Valley was isolated, China, which has a strong ability to convert cellulose to potential biofuel. In total, from five soil sample sites, six strains were isolated that grew well on CMC-Agar medium, with colony diameters ranging from 3~4 mm, among them, one strain had a strong ability to produce biofuels. Based on morphological and phylogenetic analyses, the isolate was identified as Arthrobacter nitroguajacolicus strain SLP1. The chemical properties of the biofuel extracted from the fermentation broth of strain SLP1 were analysed by gas chromatography and mass spectrometry. A total of 41 kinds of carbon compounds were identified, of those,five were detected at peak concentration and the carbon numbers ranged from C16–C22, which can be classified as alkanes,alkenes, and alcohols. Furthermore, biofuel-producing ability of strain SLP1 was enhanced using NTG mutagen. In a total of 94 mutant strains, four show the most enhanced biofuel production relative to the original strain. Biofuel production conditions were optimized by growing the four mutant strains on LB-Agar and SS-Agar medium.

Calculation and Design of Dry-type Air-core Reactor

Based on the method of compound and additional conditions under the conditions of the equal temperature rise and the equal potential drop (P.D.) of resistance, the application of design software of dry-type air-core reactor is introduced in this thesis. The analytical methods of the inductance are also given. This approach is proved entirely feasible in theory through the simplification with Bartky transformation, and is able to quickly and accurately calculate reactor inductance. This paper presents the analytical methods of the loss of dry-type air-core reactor as well.

Association among Serum Organochlorine Pesticide Residues, Glutathione S-Transferase M1 Genetic Polymorphism and Female Breast Cancer

Background: The purpose of this study was to evaluate the association among serum organochlorine pesticide residues, glutathione S-transferase M1 genetic polymorphism and female breast cancer. Methods: A 1:1 matched case-control study of 140 newly diagnosed breast cancer patients and 140 non-cancer female patients who consulted the five largest hospitals in the Tangshan city from September 2006 to October 2007. Results: The result showed higher risk of breast cancer among subjects with higher levels of serum DDT and HCH residue, the OR was 3.18 (95%CI, 1.11 - 9.07) and 5.02 (95%CI, 1.64 - 16.56).The value of ORe associated with single environmental factor DDT high residues, and ORg associated with single GSTM1 deletion genotype were respectively 3.86 (1.20 - 12.47) and 1.34 (0.36 - 5.08). The OReg associated with combined action of two factors was 5.59 (1.63 - 18.90), and the value of interaction parameters (γ) equaled 1.24. The value of ORe associated with single environmental factor HCH higher residue and ORg associated with single GSTM1 deletion genotype were respectively 2.73 (0.84 - 8.87) and 1.48 (0.49 - 4.60). The value of OReg associated with combined action of two factors was 3.87 (1.18 - 12.68), and γ equaled 1.38. Conclusion: The results indicated that breast cancer occurrence was the combined result of environmental and genetic factors. The concurrent action of GSTM1 deletion genotype and DDT/HCH enhanced the risk of breast cancer.

Partial recovery of disturbed V-J pairing profiles of T-cell receptor in people living with HIV receiving long-term antiretroviral therapy

Chronic human immunodeficiency virus(HIV) infection not only causes a gradual loss of CD4~+T cells but also leads to a disturbance of the T cell receptor(TCR) repertoire. In people living with HIV(PLWH), monitoring TCR repertoire is challenged by the inconsistency of complementarity determining region 3(CDR3) and limited cell numbers in clinical samples. Thus, a quantitative method is necessary for monitoring the TCR repertoire in PLWH.We characterized the TCR V-J pairing profile of na?ve and memory CD4~+T cells in healthy donors, HIV-infected antiretroviral therapy(ART)-na?ve patients and long-term(over5 years) ART-experienced patients by performing TCR sequencing. We developed a V-J index with 18 parameters which were subdivided into five categories(expression coverage, cumulative percentage of the top tenth percentile, diversity, intra-individual similarity and inter-individual similarity). In ART-na?ve patients, 14 of the 18 parameters were significantly altered.Long-term ART recovered ten parameters. The four unrecovered parameters were related to inter-individual similarity.Therefore, these findings indicate that long-term ART could only partially recover TCR V-J pairs and introduce newly impacted V-J pairs. Moreover, these results provide new insights into the V-J pairing of the TCR and into the disturbance of TCR repertoire in HIV infection.

Ultra-high current gain tunneling hot-electron transfer amplifier based on vertical van der Waals heterojunctions

Due to the backscattered parasitic current from the barriers,the current gain of the widely used amplifier is far from ideal.In this work,we demonstrate a vertical Au/Al2O3/BP/MoS2 tunneling hot-electron transfer amplifier with a hot-electron emitter-base junction and a p-n junction as the base-collector barrier.Fairly monoenergetic electrons traverse through the ultrathin Al2O3 dielectric via tunneling,which are accelerated and shifted to the collector region.The devices exhibit a high current on-off ratio of>105 and a high current density(JC)of∼1,000 A/cm2 at the same time.Notably,this work demonstrates a common-emitter current gain(β)value of 1,384 with a nanowatt power consumption at room temperature,which is a record high value among the all 2D based hot-electron transistors.Furthermore,the temperature dependent performance is investigated,and theβvalue of 1,613 is obtained at 150 K.Therefore,this work presents the potential of 2D based transistors for high-performance applications.

Distinct durability of IgM/IgG antibody responses in COVID-19 patients with differing severity

Dear Editor,The coronavirus disease 2019(COVID-19)pandemic is generating a demand for simultaneous vaccine development,which is expected to prevent future outbreaks by eliciting sufficient and protective immunity.

Single-cell transcriptomic analysis reveals transcript enrichment in oxidative phosphorylation,fluid sheer stress,and inflammatory pathways in obesity-related glomerulopathy

Obesity-related glomerulopathy(ORG)is an independent risk factor for chronic kid-ney disease and even progression to end-stage renal disease.Efforts have been undertaken to elucidate the mechanisms underlying the development of ORG and substantial advances have been made in the treatment of ORG,but relatively little is known about cell-specific changes in gene expression.To define the transcriptomic landscape at single-cell resolution,we analyzed kidney samples from four patients with ORG and three obese control subjects without kidney disease using single-cell RNA sequencing.We report for the first time that immune cells,including T cells and B cells,are decreased in ORG patients.Further analysis indicated that SPP1 was significantly up-regulated in T cells and B cells.This gene is related to inflammation and cell proliferation.Analysis of differential gene expression in glomerular cells(endothelial cells,mesangial cells,and podocytes)showed that these cell types were mainly enriched in genes related to oxidative phosphorylation,cell adhesion,thermogenesis,and inflammatory pathways(PI3K-Akt signaling,MAPK signaling).Furthermore,we found that the podocytes of ORG patients were enriched in genes related to the fluid shear stress pathway.Moreover,an evaluation of cell-cell communications revealed that there were interactions between glomerular parietal epithelial cells and other cells in ORG patients,with major interactions between parietal epithelial cells and podocytes.Altogether,our identification of molecular events,cell types,and differentially expressed genes may facilitate the development of new preventive or therapeutic approaches for ORG.

PD-L1:expression regulation

Programmed death-ligand 1(PD-L1),expressed on the surface of tumor cells,can bind to programmed cell death-1(PD-1)on T cells.The interaction of PD-1 and PD-L1 can inhibit T-cell responses by decreasing T-cell activity and accelerating their apoptosis.Various cancers express high levels of PD-L1 and exploit PD-L1/PD-1 signaling to evade T-cell immunity,and immunotherapies targeting the PD-1/PD-L1 axis have been shown to exert remarkable anti-tumor effects;however,not all tumor patients benefit from these therapies.Therefore,study of the mechanisms regulating PD-L1 expression are imperative.In this review,we explore regulation of PD-L1 expression in the contexts of gene transcription,signaling pathways,histone modification and remodeling,microRNAs,long noncoding RNAs,and post-translational modification.Current developments in studies of agents that block PD-L1 and correlations between immunotherapies targeting PD-1/PD-L1 and PD-L1 expression are also summarized.Our review will assist in understanding of PD-L1 expression regulation and discusses the implications of reported findings in cancer diagnosis and immunotherapy.

NPC1-regulated dynamic of clathrin-coated pits is essential for viral entry

Viruses utilize cellular lipids and manipulate host lipid metabolism to ensure their replication and spread.Therefore,the identification of lipids and metabolic pathways that are suitable targets for antiviral development is crucial.Using a library of compounds targeting host lipid metabolic factors and testing them for their ability to block pseudorabies virus(PRV)and vesicular stomatitis virus(VSV)infection,we found that U18666A,a specific inhibitor of Niemann-Pick C1(NPC1),is highly potent in suppressing the entry of diverse viruses including pseudotyped severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).NPC1 deficiency markedly attenuates viral growth by decreasing cholesterol abundance in the plasma mem-brane,thereby inhibiting the dynamics of clathrin-coated pits(CCPs),which are indispensable for clathrin-mediated endocytosis.Significantly,exogenous cholesterol can complement the dynamics of CCPs,leading to efficient viral entry and infectivity.Administration of U18666A improves the survival and pathology of PRV-and influenza A virus-infected mice.Thus,our studies demonstrate a unique mechanism by which NPC1 inhibition achieves broad antiviral activity,indicating a potential new therapeutic strategy against SARS-CoV-2,as well as other emerging viruses.

Storm of soluble immune checkpoints associated with disease severity of COVID-19

Dear Editor,As the outbreak of coronavirus disease 2019(COVID-19)turns into a pandemic,it has literally caused a worldwide public health crisis.Progressive lymphopenia,especially in T cells,was a prominent clinical feature of severe COVID-19 in addition to dyspnea,hypoxemia,acute respiratory distress,and cytokine release syndrome.1 Recently,several studies revealed a correlation between T cell depletion and increased expression levels of several inhibitory checkpoint molecules on T cells in severe COVID-19 cases.2 Classically,inhibitory checkpoint molecules have been documented as key factors for regulating T cell exhaustion in a variety of chronic viral infections and tumors.Recent studies further implied a pivotal role of inhibitory checkpoint molecules in the pathophysiology of acute viral infections,such as Ebola virus or hantavirus infection.Of note,soluble isoforms of checkpoints can be produced by cleavage of membrane-bound proteins or by alternative splicing of mRNA and competitively regulate the functions of their membrane-bound counterparts.3 Thus it is of great interest to determine whether soluble checkpoint molecules are involved in immune regulation and severity of COVID-19.

Screening and Assessing 11 Mycobacterium tuberculosis Proteins as Potential Serodiagnostical Markers for Discriminating TB Patients from BCG Vaccinees

Purified protein derivative （PPD） skin tests often yield poor specificity, so that to develop new serological antigens for distinguishing between Mycobacterium tuberculosis infection and Bacille Calmette-Guerin （BCG） vaccination is a priority, especially for developing countries like China. We predicted the antigenicity for selected open reading frames （ORFs） based on the genome sequences of M. tuberculosis H37Rv and M. boris BCG, as well as their functions and differences of expression under different stimulus. The candidate ORFs were cloned from H37Rv sequences and expressed as recombinant proteins in Escherichia coli. We studied the serodiagnostic potential of 11 purified recombinants by using enzyme-linked immunosorbent assay （ELISA） and involving a cohort composed of 58 TB patients （34 males and 24 females）, 8 healthy volunteers and 50 PPD-negative individuals before and after BCG vaccination. For all the 11 antigens, the median OD values for the sera from TB patients were statistically significantly higher than those for PPD-negative individuals before or after BCG vaccination （P〈0.01）. They had at least 92% specificity in healthy controls and six seroantigens （Rv0251c, Rv1973, Rv2376c, Rv2537c, Rv2785c and Rv3873A） were never reported with seroantigenicities previously. Thus the approach combining comparative genomics, bioinformatics and ELISA techniques can be employed to identify new seroantigens distinguishing M. tuberculosis infection from BCG vaccination.

High-current MoS transistors with non-planar gate configuration

The ever-decreasing size of transistors requires effectively electrostatic control over ultra-thin semiconductor body.Rational design of the gate configuration can fully persevere the intrinsic property of two-dimensional(2 D)semiconductors.Here we design and demonstrate a 2 D Mo S_(2) transistor with omega-shaped gate,in which the local gate coupling is enhanced by the non-planar geometry.The omega-shaped non-planar transistors exhibit a high current of 0.89 A/lm and transconductance of32.7 l S/lm.The high performance and desirable current saturation promise the construction of robust logic gate.The inverters show a voltage gain of 26.6 and an ideal total margin nearly 89%.We also assemble NOT-AND(NAND)gate on an individual Mo S_(2) flake,and the constructed NAND gate demonstrates the universal functionality of the transistors as well.This work provides an alternative strategy to fully take the advantages of 2 D materials for high-performance field-effect transistors.

Comparative Analysis of Vibration and Noise of Axial Flux Motor with Different Pole and Slot Combinations

The electromagnetic vibration noise in axial flux motors was meticulously examined.In this study,24-slot/10-pole and 12-slot/10-pole axial flux motors were chosen as the subjects of research.The spatial characteristics of the axial electromagnetic force were derived analytically and confirmed via two-dimensional Fourier decomposition.The finite-element method was used to simulate the low-order axial modes of both motors.Furthermore,a modal experiment on the stator of a 24-slot/10-pole axial flux motor was conducted to validate the simulation’s accuracy.By integrating the electromagnetic and structural models,a comprehensive multi-physical field model was developed to calculate the vibration noise of the axial flux motor.The precision of this model was subsequently corroborated with noise experiments.The findings from this study aim to offer insights into identifying the sources of vibration noise in axial flux motors.