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Signal Transduction and Targeted Therapy 2024年第6期9卷 2359-2361页

作者： Xun Wang Shujun Jiang wentai ma Yanliang Zhang Pengfei Wang Shanghai Pudong Hospital Fudan University Pudong Medical CenterState Key Laboratory of Genetic EngineeringMOE Engineering Research Center of Gene TechnologySchool of Life SciencesShanghai Institute of Infectious Disease and BiosecurityFudan UniversityShanghaiChina Department of Infectious Diseases Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese MedicineNanjing Research Center for Infectious Diseases of Integrated Traditional Chinese and Western MedicineNanjingJiangsuChina Beijing Institute of Genomics Chinese Academy of SciencesUniversity of Chinese Academy of Sciences and China National Center for BioinformationBeijingChina

Dear Editor,The rapid and widespread transmission of SARS-CoV-2 has led to the emergence of multiple variants of concern(VOCs),most notably the Omicron variant,which continues to evolve and diversify into a range of *** previous research has shown that these Omicron sub-lineages,spanning BA.1-BA.2.86,have been evolving to exhibit increased neutralization escape capabilities.

关键词： evolve neutralization variants

Genomic Perspectives on the Emerging SARS-CoV-2 Omicron Variant

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Genomics, Proteomics & Bioinformatics 2022年第1期20卷 60-69页

作者： wentai ma Jing Yang Haoyi Fu Chao Su Caixia Yu Qihui Wang Ana Tereza Ribeiro de Vasconcelos Georgii A.Bazykin Yiming Bao Mingkun Li CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China National Genomics Data Center Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China Laboratorio de Bioinformatica Laboratorio Nacional de Computacao CientıficaPetropolis 25651-075Brazil Skolkovo Institute of Science and Technology Moscow 121205Russia Kharkevich Institute for Information Transmission Problems of the Russian Academy of Sciences Moscow 127051Russia Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunming 650201China

A new variant of concern for SARS-CoV-2,Omicron(B.1.1.529),was designated by the World Health Organization on November 26,*** study analyzed the viral genome sequencing data of 108 samples collected from patients infected with ***,we found that the enrichment efficiency of viral nucleic acids was reduced due to mutations in the region where the primers anneal ***,the Omicron variant possesses an excessive number of mutations compared to other variants circulating at the same time(median:62 vs.45),especially in the Spike *** in the Spike gene confer alterations in 32 amino acid residues,more than those observed in other SARS-CoV-2 ***,a large number of nonsynonymous mutations occur in the codons for the amino acid residues located on the surface of the Spike protein,which could potentially affect the replication,infectivity,and antigenicity of ***,there are 53 mutations between the Omicron variant and its closest sequences available in public *** of these mutations were rarely observed in public databases and had a low mutation *** addition,the linkage disequilibrium between these mutations was low,with a limited number of mutations concurrently observed in the same genome,suggesting that the Omicron variant would be in a different evolutionary branch from the currently prevalent *** improve our ability to detect and track the source of new variants rapidly,it is imperative to further strengthen genomic surveillance and data sharing globally in a timely manner.

关键词： Omicron Genomics Mutation Variant of concern SARS-CoV-2

Characteristics of replication and pathogenicity of SARS-CoV-2 Alpha and Delta isolates

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Virologica Sinica 2022年第6期37卷 804-812页

作者： Xiao-Li Feng Dandan Yu Mi Zhang Xiaohong Li Qing-Cui Zou wentai ma Jian-Bao Han Ling Xu Cuixian Yang Wang Qu Zhong-Hua Deng Junyi Long Yanghaopeng Long Mingkun Li Yong-Gang Yao Xing-Qi Dong Jianxiong Zeng Ming-Hua Li Kunming National High-level Biosafety Research Center for Non-Human Primates Center for Biosafety Mega-ScienceKunming Institute of ZoologyChinese Academy of SciencesKunming650107China Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesKunming Institute of ZoologyChinese Academy of SciencesKunming650201China National Resource Center for Non-Human Primates National Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)Kunming Institute of ZoologyChinese Academy of SciencesKunming650107China Department of Infectious Diseases Yunnan Provincial Infectious Diseases HospitalKunming650301China Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciencesand China National Center for BioinformationBeijing100101China University of Chinese Academy of Sciences Beijing100049China Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunming650201China Kunming College of Life Science University of Chinese Academy of SciencesKunming650204China Yunnan Key Laboratory of Biodiversity Information Kunming Institute of ZoologyChinese Academy of SciencesKunming650201China

The continuously arising of SARS-CoV-2 variants has been posting a great threat to public health safety globally,from B.1.17(Alpha), B.1.351(Beta), P.1(Gamma), B.1.617.2(Delta) to B.1.1.529(Omicron). The emerging or reemerging of the SARS-CoV-2 variants of concern is calling for the constant monitoring of their epidemics,pathogenicity and immune escape. In this study, we aimed to characterize replication and pathogenicity of the Alpha and Delta variant strains isolated from patients infected in Laos. The amino acid mutations within the spike fragment of the isolates were determined via sequencing. The more efficient replication of the Alpha and Delta isolates was documented than the prototyped SARS-CoV-2 in Calu-3 and Caco-2 cells, while such features were not observed in Huh-7, Vero E6 and HPA-3 cells. We utilized both animal models of human ACE2(hACE2)transgenic mice and hamsters to evaluate the pathogenesis of the isolates. The Alpha and Delta can replicate well in multiple organs and cause moderate to severe lung pathology in these animals. In conclusion, the spike protein of the isolated Alpha and Delta variant strains was characterized, and the replication and pathogenicity of the strains in the cells and animal models were also evaluated.

关键词： SARS-CoV-2 Variants of concern(VOC) Alpha Delta hACE2 transgenic mice Hamster

Dynamics of severe acute respiratory syndrome coronavirus 2 genome variants in the feces during convalescence

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Journal of Genetics and Genomics 2020年第10期47卷 610-617页

作者： Yi Xu Lu Kang Zijie Shen Xufang Li Weili Wu wentai ma Chunxiao Fang Fengxia Yang Xuan Jiang Sitang Gong Li Zhang Mingkun Li Department of Pediatrics Guangzhou Women and Children's Medical CenterGuangzhou Medical UniversityGuangzhou510623China Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesChina National Center for BioinformationBeijing101300China University of Chinese Academy of Sciences Beijing100049China Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunming650223China

In response to the current coronavirus disease 2019(COVID-19)pandemic,it is crucial to understand the origin,transmission,and evolution of severe acute respiratory syndrome coronavirus 2(SARS-Co V-2),which relies on close surveillance of genomic diversity in clinical *** the mutation at the population level had been extensively investigated,how the mutations evolve at the individual level is largely *** time-series fecal samples were collected from nine patients with COVID-19 during the convalescent *** nucleic acids of SARS-CoV-2 were enriched by the hybrid capture ***,we demonstrated the outstanding performance of the hybrid capture method in detecting intra-host *** identified 229 intra-host variants at 182 sites in 18 fecal *** them,nineteen variants presented frequency changes>0.3 within 1-5 days,reflecting highly dynamic intrahost viral ***,the evolution of the viral genome demonstrated that the virus was probably viable in the gastrointestinal tract during the convalescent ***,we also found that the same mutation showed a distinct pattern of frequency changes in different individuals,indicating a strong random *** summary,dramatic changes of the SARS-CoV-2 genome were detected in fecal samples during the convalescent period;whether the viral load in feces is sufficient to establish an infection warranted further investigation.

关键词： SARS-CoV-2 Intra-host variant Dynamics Mutation Hybrid capture

Temporal dynamics of SARS-CoV-2 genome mutations that occurred in vivo on an aircraft

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Biosafety and Health 2023年第1期5卷 62-67页

作者： Yaqing He Shengyuan Dang wentai ma Long Chen Renli Zhang Shujiang Mei Xinyi Wei Qiuying Lv Bo Peng Ying Sun Dongfeng Kong Jiancheng Chen Shimin Li Xiujuan Tang Qingju Lu Can Zhu Zhigao Chen Jia Wan Xuan Zou Mingkun Li Tiejiang Feng Lili Ren Jianwei Wang Shenzhen Research Center for Communicable Disease Control and Prevention Chinese Academy of Medical SciencesShenzhen 518055China Center for Disease Control and Prevention Shenzhen 518055China National Health Commission of the People’s Republic of China Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory Institute of Pathogen BiologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China University of Chinese Academy of Sciences Beijing 100190China Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciencesand China National Center for BioinformationBeijing 100101China Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunming 650223China Key Laboratory of Respiratory Disease Pathogenomics Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

We analyzed variations in the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)genome during a flight-related cluster outbreak of coronavirus disease 2019(COVID-19)in Shenzhen,China,to explore the characteristics of SARS-CoV-2 transmission and intra-host single nucleotide variations(iSNVs)in a confined ***-three patients with COVID-19 were sampled,and 14 were resampled 3-31 days *** 47 nasopharyngeal swabs were *** and similarities in the consensus genome sequence were *** SARS-CoV-2 variants of concern,Delta(n=31),Beta(n=1),and C.1.2(n=1),were detected among the 33 *** viral genome sequences from 30 Delta-positive patients had similar SNVs;14 of these patients provided two successive ***,the 47 sequenced genomes contained 164 *** the 14 paired(successive)samples,the second samples(T2)contained more iSNVs(median:3;95%confidence interval[95%CI]:2.77-10.22)than did the first samples(T1;median:2;95%CI:1.63-3.74;Wilcoxon test,P=0.021).38 iSNVs were detected in T1 samples,and only seven were also detectable in T2 ***,T2 samples from two of the 14 paired samples had additional mutations than the T1 *** iSNVs of the SARS-CoV-2 genome exhibited rapid dynamic changes during a flight-related cluster outbreak ***-host diversity increased gradually with time,and new site mutations occurred in vivo without a population transmission ***,we could not determine the generational relationship from the mutation site changes alone.

关键词： SARS-CoV-2 Cluster epidemic Intra-host single nucleotide variation

Genomic Epidemiology of SARS-CoV-2 in Pakistan

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Genomics, Proteomics & Bioinformatics 2021年第5期19卷 727-740页

作者： Shuhui Song Cuiping Li Lu Kang Dongmei Tian Nazish Badar wentai ma Shilei Zhao Xuan Jiang Chun Wang Yongqiao Sun Wenjie Li Meng Lei Shuangli Li Qiuhui Qi Aamer Ikram Muhammad Salman massab Umair Huma Shireen Fatima Batool Bing Zhang Hua Chen Yun-Gui Yang Amir Ali Abbasi Mingkun Li Yongbiao Xue Yiming Bao China National Center for Bioinformation Beijing 100101China National Genomics Data Center Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China CAS Key Laboratory of Genome Sciences and Information Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China Department of Virology and Immunology National Institute of HealthIslamabad 45500Pakistan National Center for Bioinformatics Programme of Comparative and Evolutionary GenomicsFaculty of Biological SciencesQuaid-i-Azam UniversityIslamabad 45320Pakistan Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunming 650223China State Key Laboratory of Plant Cell and Chromosome Engineering Institute of Genetics and Developmental BiologyThe Innovation Academy of Seed DesignChinese Academy of SciencesBeijing 100101China

COVID-19 has swept globally and Pakistan is no *** investigate the initial introductions and transmissions of the SARS-CoV-2 in Pakistan,we performed the largest genomic epidemiology study of COVID-19 in Pakistan and generated 150 complete SARS-CoV-2 genome sequences from samples collected from march 16 to June 1,*** identified a total of 347 mutated positions,31 of which were over-represented in ***,we found over 1000 intra-host single-nucleotide variants(iSNVs).Several of them occurred concurrently,indicating possible interactions among them or *** of the high-frequency iSNVs in Pakistan were not observed in the global population,suggesting strong purifying *** genomic epidemiology revealed five distinctive spreading *** largest cluster consisted of 74 viruses which were derived from different geographic locations of Pakistan and formed a deep hierarchical structure,indicating an extensive and persistent nation-wide transmission of the virus that was probably attributed to a signature mutation(G8371T in ORF1ab)of this ***,28 putative international introductions were identified,several of which are consistent with the epidemiological *** all,this study has inferred the possible pathways of introductions and transmissions of SARS-CoV-2 in Pakistan,which could aid ongoing and future viral surveillance and COVID-19 control.

关键词： SARS-CoV-2 Virus Molecular evolution Haplotype network Pakistan

Cold-chain food contamination as the possible origin of COVID-19 resurgence in Beijing

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National Science Review 2020年第12期7卷 1861-1864页

作者： Xinghuo Pang Lili Ren Shuangsheng Wu wentai ma Jian Yang Lin Di Jie Li Yan Xiao Lu Kang Shichang Du Jing Du Jing Wang Gang Li Shuguang Zhai Lijuan Chen Wenxiong Zhou Shengjie Lai Lei Gao Yang Pan Quanyi Wang Mingkun Li Jianbin Wang Yanyi Huang Jianwei Wang COVID-19 Field Response Group COVID-19 Laboratory Testing Group World Pop School of Geography and Environmental ScienceUniversity of Southampton Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences Beijing Advanced Innovation Center for Structural Biology(ICSB) Tsinghua University Chinese Institute for Brain Research(CIBR) Institute for Cell Analysis Shenzhen Bay Laboratory Beijing Center for Disease Prevention and Control(CDC) Research Centre for Preventive Medicine of Beijing NHC Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory Institute of Pathogen BiologyChinese Academy of Medical Sciences & Peking Union Medical College Key Laboratory of Respiratory Disease Pathogenomics Chinese Academy of Medical Sciences and Peking Union Medical College Beijing Institute of Genomics Chinese Academy of Sciencesand China National Center for Bioinformation University of Chinese Academy of Sciences NHC Key Laboratory of Systems Biology of Pathogens Institute of Pathogen BiologyChinese Academy of Medical Sciences & Peking Union Medical College Beijing Advanced Innovation Center for Genomics (ICG) Biomedical Pioneering Innovation Center (BIOPIC)College of Chemistryand Peking-Tsinghua Center for Life SciencesPeking University School of Life Sciences Tsinghua-Peking Center for Life SciencesTsinghua University

COVID-19,caused by SARS-CoV-2[1,2],has been contained in China through stringent non-pharmaceutical *** control and quarantine have effectively prevented the virus from being spread by infected travellers,but the risk...

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“以患者为中心”临床结局评估的选择与开发

中国循证医学杂志 2024年第4期24卷 472-477页

作者：张晨瑶吴晓蕾史梦龙马毓聪庞稳泰杜亮刘炳林曹璐佳张俊华天津中医药大学循证医学中心天津301617 四川大学华西医院中国循证医学中心成都610041 国家药品监督管理局药品审评中心北京100022

为了在临床试验中充分考虑患者相关因素,美国食品和药品监督管理局制定了一系列“以患者为中心的药物研发”的指导原则。本文围绕指导原则3“选择与研发合适的临床结局评估”,对临床结局评估的内涵、研制流程、评分机制、干扰因素及敏... 详细信息

为了在临床试验中充分考虑患者相关因素,美国食品和药品监督管理局制定了一系列“以患者为中心的药物研发”的指导原则。本文围绕指导原则3“选择与研发合适的临床结局评估”,对临床结局评估的内涵、研制流程、评分机制、干扰因素及敏感性五个方面进行概述,并介绍四种常见类型的临床结局评估,为以患者为中心的临床试验结局评价工作实施提供参考。

关键词：以患者为中心药物研发临床结局评估

Volatile organic compounds in wintertime North China Plain:Insights from measurements of proton transfer reaction time-of-flight mass spectrometer(PTR-ToF-MS)

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Journal of Environmental Sciences 2022年第4期34卷 98-114页

作者： Xianjun He Bin Yuan Caihong Wu Sihang Wang Chaomin Wang Yibo Huangfu Jipeng Qi Nan ma Wanyun Xu Ming Wang wentai Chen Hang Su Yafang Cheng Min Shao Institute for Environmental and Climate Research Jinan UniversityGuangzhou 511443China Guangdong-Hongkong-macao Joint Laboratory of Collaborative Innovation for Environmental Quality Guangzhou 511443China State Key Laboratory of Severe Weather&Key Laboratory for Atmospheric Chemistry of China Meteorology Administration Chinese Academy of Meteorological SciencesBeijing 100081China Collaborative Innovation Center of Atmospheric Environment and Equipment Technology Jiangsu Key Laboratory of Atmospheric Environment Monitoring and Pollution ControlSchool of Environmental Science and EngineeringNanjing University of Information Science&TechnologyNanjing 210044China Nanjing Intelligent Environmental Science and Technology Co. Ltd.Nanjing 211800China max Planck Institute for Chemistry Mainz 55128Germany

The characteristics of wintertime volatile organic compounds(VOCs)in the North China Plain(NCP)region are complicated and remain *** measurements were conducted by a proton transfer reaction time-of-flight mass spectrometer(PTR-ToF-MS)at a rural site in the NCP from November to December *** ions measured by PTRToF-MS were quantified and the overall VOC compositions were investigated by combining the measurements of PTR-ToF-MS and gas chromatography-mass spectrometer/flame ionization detector(GC-MS/FID).The measurement showed that although atmospheric VOCs concentrations are often dominated by primary emissions,the secondary formation of oxygenated VOCs(OVOCs)is non-negligible in the wintertime,i.e.,OVOCs accounts for 42%±7%in the total VOCs(151.3±75.6 ppbV).We demonstrated that PTR-MS measurements for isoprene are substantially overestimated due to the interferences of *** chemical changes of organic carbon in a pollution accumulation period were investigated,which suggests an essential role of fragmentation reactions for large,chemically reduced compounds during the heavy-polluted stage in wintertime *** changes of emission ratios of VOCs between winter 2011 and winter 2018 in the NCP support the positive effect of“coal to gas”strategies in curbing air *** high abundances of some key species(*** aromatics)indicate the strong emissions of coal combustion in wintertime of *** ratio of naphthalene to C8 aromatics was proposed as a potential indicator of the influence of coal combustion on VOCs.

关键词： North China Plain Volatile organic compound Wintertime PTR-ToF-MS

Crosstalk in polymer microelectrode arrays

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Nano Research 2021年第9期14卷 3240-3247页

作者： Yi Qiang Wen Gu Zehua Liu Shanchuan Liang Jae Hyeon Ryu Kyung Jin Seo wentai Liu Hui Fang Department of Electrical and Computer Engineering Northeastern UniversityBostonMA 02115USA Department of Bioengineering University of CaliforniaLos AngelesLos AngelesCA 90095USA Department of Bioengineering Northeastern UniversityBostonMA 02115USA

Thin-film polymer microelectrcxje arrays(MEAs)facilitate the high-resolution neural recording with its superior mechanical ***,the densely packed electrodes and interconnects along with the ultra-thin polymeric encapsulation/substrate layers give rise to non-negligible crosstalk,which could result in severe interference in the neural signal *** to the lack of standardized characterization or modeling of crosstalk in neural electrode arrays,to date,crosstalk in polymer MEAs remains poorly *** this work,the crosstalk between two adjacent polymer microelectrodes is measured experimentally and modeled using equivalent ***,this study demonstrated a two-well measuring platform and systematically characterized the crosstalk in polymer microelectrodes with true isolation of the victim channel and precise control of its grounding condition.A simple,unified equation from detailed circuit modeling was proposed to calculate the crosstalk in different *** element analysis(FEA)analysis was conducted further to explore the crosstalk in more aggressively scaled polymer electrode *** addition to standardizing neural electrode array crosstalk characterization,this study not only reveals the dependence of the crosstalk in polymer MEAs on a variety of key device parameters but also provides general guidelines for the design of thin polymer MEAs for high-quality neural signal recording.

关键词： crosstalk effect flexible microelectrodes equivalent circuit modelling finite element analysis polymer