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IDH1 mutation inhibits differentiation of astrocytes and glioma cells with low oxoglutarate dehydrogenase expression by disturbingα-ketoglutarate-related metabolism and epigenetic modification

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Life Metabolism 2024年第2期3卷 24-37页

作者： Yuanlin Zhao Ying Yang Risheng Yang Chao Sun Xing Gao Xiwen Gu Yuan Yuan Yating Nie Shenhui Xu Ruili Han Lijun Zhang Jing Li Peizhen Hu Yingmei Wang Huangtao Chen Xiangmei Cao Jing Wu Zhe Wang Yu Gu Jing Ye State Key laboratory of Holistic Integrative Management of Gastrointestinal Cancers Department of PathologyXijing Hospital and School of Basic MedicineFourth Military Medical UniversityXi’anShaanxi 710032China Department of Pathology Air Force Hospital of Southern Theater CommandGuangzhouGuangdong 510000China Department of Neurology Tangdu HospitalFourth Military Medical UniversityXi’anShaanxi 710038China Department of Clinical diagnosis Tangdu HospitalFourth Military Medical UniversityXi’anShaanxi 710038China Department of Neurosurgery the Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’anShaanxi 710004China Department of Pathology School of Basic Medical SciencesNingxia Medical UniversityYinchuanNingxia 750004China Institute of Analytical Chemistry and Instrument for Life Science The Key Laboratory of Biomedical Information Engineering of Ministry of EducationSchool of Life Science and TechnologyXi’an Jiaotong UniversityXi’anShaanxi 710049China

Isocitrate dehydrogenase(IDH)mutations frequently occur in lower-grade gliomas and secondary *** IDHs exhibit a gain-of-function activity,leading to the production of D-2-hydroxyglutarate(D-2HG)by reducing α-ketoglutarate(α-KG),a central player in metabolism and epigenetic ***,the role ofα-KG homeostasis in IDH-mutated gliomagenesis remains *** this study,we found that low expression of oxoglutarate dehydrogenase(OGDH)was a common feature in IDH-mutated gliomas,as well as *** low expression of OGDH resultedin the accumulation of α-KG and promoted astrocyte ***,IDH1 mutation significantly reducedα-KG levels and increased glutaminolysis and DNA/histone methylation in *** metabolic and epigenetic alterations inhibited astrocyte maturation and led to cortical dysplasia in ***,our results also indicated that reduced OGDH expression can promote the differentiation of glioma cells,while IDH1 mutations impeded the differentiation of glioma cells with low OGDH by reducing the accumulation ofα-KG and increasing ***,we found that l-glutamine increasedα-KG levels and augmented the differentiation-promoting effects of AGI5198,an IDH1-mutant inhibitor,in IDH1-mutant glioma ***,this study reveals that low OGDH expression is a crucial metabolic characteristic of IDH-mutant gliomas,providing a potential strategy for the treatment of IDH-mutant gliomas by targetingα-KG homeostasis.

关键词： α-ketoglutarate IDH1 mutation OGDH l-glutamine gliomas

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TMB相关免疫浸润调控评分(MOTIF)预测免疫治疗响应并指导联合增效

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Science Bulletin 2024年第6期69卷 803-822页

作者：钱政宇潘艺芊李薛鑫陈衍行吴灏祥刘泽先 Martin Kosar Jiri Bartek 王梓贤徐瑞华 Department of Medical Oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangdong Provincial Clinical Research Center for CancerResearch Unit of Precision Diagnosis and Treatment for Gastrointestinal CancerChinese Academy of Medical SciencesGuangzhou 510060China Science for Life laboratory Division of Genome BiologyDepartment of Medical Biochemistry and BiophysicsKarolinska InstituteStockholm S-17121Sweden Department of General Surgery The Fourth Affiliated HospitalChina Medical UniversityShenyang 110032China Bioinformatics Platform Sun Yat-sen University Cancer CenterGuangzhou 510060China Zhejiang University-University of Edinburgh Institute Zhejiang University School of MedicineHaining 314400China Edinburgh Medical School Biomedical SciencesCollege of Medicine and Veterinary MedicineThe University of EdinburghEdinburgh EH11LTUK Danish Cancer Society Research Center Copenhagen DK-2100Denmark laboratory of Artificial Intelligence and Data Science Sun Yat-sen University Cancer CenterGuangzhou 510060China

Patients with high tumor mutational burden(TMB)levels do not consistently respond to immune checkpoint inhibitors(ICIs),possibly because a high TMB level does not necessarily result in adequate infiltration of CD8^(+)T *** bulk ribonucleic acid sequencing(RNA-seq)data from 9311 tumor samples across 30 cancer types,we developed a novel tool called the modulator of TMB-associated immune infiltration(MOTIF),which comprises genes that can determine the extent of CD8^(+)T cell infiltration prompted by a certain TMB *** confirmed that MOTIF can accurately reflect the integrity and defects of the cancer-immunity *** analyzing 84 human single-cell RNA-seq datasets from 32 types of solid tumors,we revealed that MOTIF can provide insights into the diverse roles of various cell types in the modulation of CD8^(+)T cell *** pretreatment RNA-seq data from 13 ICI-treated cohorts,we validated the use of MOTIF in predicting CD8^(+)T cell infiltration and ICI *** the components of MOTIF,we identified EMC3 as a negative regulator of CD8^(+)T cell infiltration,which was validated via in vivo ***,MOTIF provided guidance for the potential combinations of programmed death 1 blockade with certain immunostimulatory drugs to facilitate CD8^(+)T cell infiltration and improve ICI efficacy.

关键词： Tumor mutational burden Immunotherapy Cancer-immunity cycle treatment efficacy prediction CD8^(+)T cell infiltration Combination therapy

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Zero-Shot Medical Image Retrieval for Emerging Infectious diseases Based on Meta-Transfer Learning--Worldwide,2020

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China CDC weekly 2020年第52期2卷 1004-1008页

作者： Yuying Zhao Hanjiang Lai Jian Yin Yewu Zhang Shigui Yang Zhongwei Jia Jiaqi Ma School of Computer Science and engineering Sun Yat-Sen UniversityGuangzhouGuangdongChina Center for Public Health Surveillance and Information Service Chinese Center for Disease Control and PreventionBeijingChina State Key laboratory for diagnosis and treatment of Infectious diseases Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiangChina School of Public Health Peking UniversityBeijingChina

Introduction:Due to the increasing number of medical images,image retrieval has become an important technique for medical image *** many content-based image retrieval methods have been proposed,the retrieval of images in datasets related to emerging/new infectious diseases still remain a challenge-mostly due to the lack of historical *** a result,the current retrieval models have limited functionality in helping doctors make accurate diagnoses of new ***:In this paper,we propose a zero-shot retrieval model based on meta-learning and ensemble learning,which can obtain a model with stronger generalizability without using any relevant training data,and thus performs well on new types of test ***:The experimental results showed that the proposed method is 3% to 5% higher than the traditional method,which means that our model can retrieve relevant medical images more accurately for newly emerging data types and provide doctors with more effective ***:When a new infectious disease occurs,doctors can use the proposed zero-shot retrieval model to retrieve all relevant cases,quickly find the common problems of patients,find the locations of the new infections,and determine its infectivity as soon as *** proposed method is a new computeraided decision support technology for emerging infectious diseases.

关键词： Image image retrieval

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Immunological Evaluation of a Novel Mycobacterium tuberculosis Antigen Rv0674

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Biomedical and Environmental Sciences 2019年第6期32卷 427-437页

作者： XIAO Tong Yang LIU Hai Can LI Xiao Qin HUANG Ming Xiang LI Gui Lian LI Na YAN Yu Han LUO Qiao WANG Xue Zhi LI Ma Chao WAN Kang Lin State Key laboratory for Infectious diseases Prevention and Control Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases National Institute for Communicable Disease Control and Prevention Chinese Center for Disease Control and Prevention Beijing 102206 China Key laboratory of laboratory Medicine Ministry of Education College of Laboratory Medicine and Life Sciences Wenzhou Medical University Wenzhou 325035 Zhejiang China Clinical laboratory Fuzhou Pulmonary Hospital Fuzhou 350008 Fujian China The first hospital of Changsha Changsha 410005 Hunan China Key laboratory of Translational Medicine of guangdong Center for Tuberculosis Control of Guangdong Province Guangzhou 510630 Guangdong China

Objective This study aimed to characterize the diagnostic and vaccine potential of a novel Mycobacterium tuberculosisantigen Rv0674. Methods To evaluate thediagnostic potential and antigenicity of Rv0674, IgG was evaluated using ELISA and interferon (IFN)-γ was done by using ELISpot assay among TB patients and healthy donors. For immunogenicity evaluation, BALB/c mice were immunized with Rv0674. Cytokine production was determined by cytokine release assay using an ELISA kit, and the antibodies were tested using ELISA. Results The results of serum Elisa tests showed that Rv0674 specific immunoglobulin G (IgG) response was higher in TB patients than negative controls. And Rv0674 had good performance in serological test with sensitivity and specificity of 77.1% and 81.1%, respectively. While it shows poor sensitivity and specificity of 26.23% and 79.69% for IFN-γ tests. In BALB/c mice, Rv0674 adjuvant by DDA/PolyI:C could also induce a high level of IFN-γ, interleukin-2 and interleukin-6 as well as a high IgG titer in both high-and low-dose groups indicating that Rv0674 is essential in humoral and cellular immunity. Moreover, the cytokine profile and IgG isotypecharacterized Rv0674 as a Th1/Th2-mixed-type protective immunity with the predominance of Th1 cytokines. Conclusion Rv0674 may be a good potential candidate for the development of TB serological diagnosis and a new TB vaccine.

关键词： Antigen Immunologic diagnosis Mycobacterium tuberculosis Rv0674 Vaccine

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Predicting the Incident Cases of Emerging Infectious Disease Using a Bayesian Probability Model--China,February 2020

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China CDC weekly 2020年第52期2卷 999-1003页

作者： Yewu Zhang Xiaofeng Wang Yanfei Li Siyu Wu Ming Wan Xuemei Su Shigui Yang Hanjiang Lai Zhongwei Jia Jiaqi Ma Center for Public Health Surveillance and Information Service Chinese Center for Disease Control and PreventionBeijingChina School of Public Health Peking UniversityBeijingChina State Key laboratory for diagnosis and treatment of Infectious diseases Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiangChina Sun Yat-sen University GuangzhouGuangdongChina

What is already known about this topic?The exact number of incident cases of emerging infectious diseases on a daily basis is of great importance to the disease control and prevention,but it is not directly available from the current surveillance system in *** is added by this report?In this study,a Bayesian statistical method was proposed to estimate the posterior parameters of the gamma probability distribution of the lag time between the onset date and the reporting time based on the surveillance *** then the posterior parameters and corresponding cumulative gamma probability distribution were used to predict the actual number of new incident cases and the number of unreported cases per *** proposed method was used for predicting COVID-19 incident cases from February 5 to February 26,*** final results show that Bayesian probability model predictions based on data reported by February 28,2020 are very close to those actually reported a month *** are the implications for public health practice?This research provides a Bayesian statistical approach for early estimation of the actual number of cases of incidence based on surveillance data,which is of great value in the prevention and control practice of epidemics.

关键词： prevention Probability incident

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Quantitative analysis of retinal intermediate and deep capillary plexus in patients with retinal deep vascular complex ischemia

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International Journal of Ophthalmology(English edition) 2021年第7期14卷 1025-1033页

作者： Xin-Xin Li Tian-Wei Qian Ya-Nan Lyu Xun Xu Su-Qin Yu Department of Ophthalmology Shanghai General HospitalShanghai Jiao Tong UniversityShanghai 200080China national Clinical Research Center for Eye diseases Shanghai Key Laboratory of Ocular Fundus DiseaseShanghai 200080China Shanghai engineering Center for Visual Science and Photomedicine Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye DiseasesShanghai 200080China

AIM: To quantitatively analyze the retinal intermediate and deep capillary plexus(ICP and DCP) in patients with retinal deep vascular complex ischemia(RDVCI), using 3D projection artifacts removal(3D PAR) optical coherence tomography angiography(OCTA).METHODS: RDVCI patients and gender-and agematched healthy controls were assessed and underwent OCTA examinations. The parafoveal vessel density(PFVD) of retinal deep vascular complex(DVC), ICP, and DCP were analyzed, and the percentage of reduction(PR) of PFVD was ***: Twenty-four eyes in 22 RDVCI patients(20 in acute phase and 4 in chronic phase) and 24 eyes of 22 healthy subjects were enrolled as the control group. Significant reduction of PFVD in DVC, ICP, and DCP was observed in comparison with the controls(DVC: acute: 43.59%±6.58% vs 49.92%±5.49%, PR=12.69%;chronic: 43.50%±3.33% vs 51.20%±3.80%, PR=15.04%. ICP: acute: 40.28%±7.91% vs 46.97%±7.14%, PR=14.23%;chronic: 41.48%±2.87% vs 46.43%±3.29%, PR=10.66%. DCP: acute: 45.44%±8.27% vs 51.51%±9.97%, PR=11.79%;chronic: 37.78%±3.48% vs 51.73%±5.17%, PR=26.97%;all P<0.05). No significant PR difference was found among DVC, ICP, and DCP of RDVCI in acute phase(P=0.812), but significant difference in chronic phase(P=0.006, DVC vs DCP, ICP vs DCP). No significant difference in PR between acute and chronic phases in the DVC(P=0.735) or ICP(P=0.681) was found, but significant difference in the DCP(P=0.041).CONCLUSION: The PFVD of DVC, ICP, and DCP in RDVCI is significantly decreased in both acute and chronic phases. ICP impairment is stabilized from acute to chronic phase in RDVCI, whereas subsequent DCP impairment is uncovered and can be explained by ischemia-reperfusion damage.

关键词： intermediate and deep capillary plexus 3D projection artifacts removal optical coherence tomography angiography retinal deep vascular complex ischemia

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IL-17A-dependent gut microbiota is essential for regulating diet-induced disorders in mice

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Science Bulletin 2017年第15期62卷 1052-1063页

作者： Yujing Bi Chunxiao Li Lin Liu Jiyuan Zhou Zhengchao Li Huimin Deng Chunyan Wu Yanping Han Yajun Song Yafang Tan Xiaoyi Wang Zongmin Du Yujun Cui Yanfeng Yan Fachao Zhi Guangwei Liu Nan Qin Heping Zhang Ruifu Yang State Key laboratory of Pathogen and Biosecurity. Beijing Institute of MicrobiologY and Epidemiology Beijing 100071 China Key laboratory of Cell Proliferation and Regulation Biology Ministry of Education Institute of Cell Biology College of Life Science Beijing Normal University Beijing 100875 China State Key laboratory for diagnosis and treatment of Infectious Disease The First Affiliated Hospital College of Medicine Zhejiang University Hangzhou 310003 China Collaborative Innovation Center for diagnosis and treatment of Infectious diseases Zhejiang University Hangzhou 310003 China guangdong Provincial Key laboratory of Gastroenterology Institute of Gastroenterology of Guangdong Province Department of Gastroenterology Nan fang Hospital Southern Medical University Guangzhou 510515 China Realbio Genomics Institute Shanghai 200050 China Key laboratory of Dairy Biotechnology and engineering Education Ministry of China Inner Mongolia Agricultural University Hohhot 010018 China

The gut microbiota plays a key role in obesity and related metabolic disorders, and multiple factors including diet, host genotype, and age regulate it. Many studies have examined the contribution of extrinsic factors to the regulation of the gut microbiota, but the importance of the host genetic constitution cannot be ignored, lnterleukin 17A （lL-17A）, a pro-inflammatory cytokine, is important in the defense against infection and diseases. Here, we investigated the association among IL-17, a high-fat diet （HFD）, and the gut microbiota. Mice deficient in 1L-17A were resistant to diet-induced obesity and related diseases. Compared with the I1-17a^-/1 mice, wild-type （WT） mice challenged with HFD showed obvious weight fluctuations, such as those seen in type 2 diabetes, and hematological changes similar to those associated with metabolic syndrome. However, housing WT mice and Il-17a^-/- mice together signifi- cantly alleviated these symptoms in the WT mice. A metagenomic analysis of the mouse feces indicated that the microbial community compositions of these two groups differed before HFD feeding. The HFD mediated shifts in the gut microbial compositions, which were associated with the mouse phenotypes. We also identified potentially beneficial and harmful species present during this period, and drew net- works of the most abundant species. A functional analysis indicated pathway changes in the WT and I1-17a^- /- mice when fed the HFD. Collectively, these data underscore the importance of the host factor IL-17A in shaping and regulating the gut microbiota, which conversely, influences the host health.

关键词： Gut microbiota Obesity IL-17A Metagenomics

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Genetic polymorphisms in pri-let-7a-2 are associated with ischemic stroke risk in a Chinese Han population from Liaoning, China: a case-control study

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Neural Regeneration Research 2021年第7期16卷 1302-1307页

作者： Yu-Ye Wang He-Yu Zhang Wen-Juan Jiang Fang Liu Lei Li Shu-Min Deng Zhi-Yi He Yan-Zhe Wang Department of Neurology Key Laboratory for Neurological Big Data of Liaoning ProvinceThe First Affiliated Hospital of China Medical UniversityShenyangLiaoning ProvinceChina Department of Neurology The First Affiliated HospitalSun Yat-sen University/Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological DiseasesNational Key Clinical Department and Key Discipline of NeurologyGuangzhouGuangdong ProvinceChina Department of Pharmacology School of PharmacyChina Medical UniversityShenyangLiaoning ProvinceChina

Ischemic stroke is a complicated disease, and its pathogenesis has been attributed to the occurrence of genetic *** has suggested that the microRNA let-7a is involved in the pathogenesis of ischemic ***-miRNA is the primary transcript, which undergoes several processing steps to generate pre-miRNA and, later, mature *** this case-control study, we analyzed the distribution of prilet-7a-2 variants in patients at a high risk for ischemic stroke and the interactions of pri-let-7a-2 variants and environmental *** samples and clinical information were collected from 1086 patients with ischemic stroke and 836 healthy controls between December 2013 and December 2015 at the First Affiliated Hospital of China Medical *** found that the rs1143770 CC genotype and the C allele were associated with a decreased risk of ischemic stroke, whereas the rs629367 CC genotype was associated with an increased risk for ischemic ***, these two single-nucleotide polymorphisms were in linkage disequilibrium in this study *** analyzed gene-environment interactions and found that rs1143770 exerted a combined effect on the pathogenesis of ischemic stroke, together with alcohol use, smoking, and a history of ***, the detection of pri-let-7a-2 polymorphisms may increase the awareness of ischemic stroke *** study was approved by the Institutional Ethics Committee of the First Affiliated Hospital of China Medical University, China(approval No.2012-38-1) on February 20, 2012, and was registered with the Chinese Clinical Trial Registry(registration number: ChiCTR-COC-17013559) on December 27, 2017.

关键词： case-control study Chinese Han population ischemic stroke pri-micro RNA pri-let-7a-2 risk factors rs1143770 rs629367 single-nucleotide polymorphism single-nucleotide polymorphism-environment interaction

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Genetic and Antibiotic Resistance Characteristics ofCampylobacterjejuni Isolated from Diarrheal Patients,Poultry and Cattle in Shenzhen

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Biomedical and Environmental Sciences 2018年第8期31卷 579-585页

作者： JU Chang Yan ZHANG Mao Jun MA Yan Ping LU Jing Rang YU Mu Hua CHEN Hui LIU Chu Yun GU Yi Xin FU Yan Yan DUAN Yong Xiang Nanshan Center for Disease Control and Prevention Shenzhen 518054GuangdongChina State Key laboratory of Infectious Disease Prevention and Control Collaborative Innovation Center for Diagnosis and Treatment ofInfectious DiseasesNational Institute for Communicable Disease Control and PreventionChinese Center for DiseaseControl and PreventionBeijing 102206China ORD Environmental Protection AgencyCincinnatiOhio 45220United States

Objective To investigate genetic and antibiotic resistance characteristics of Campylobacter jejuni(C. jejuni) isolated from Shenzhen. Methods Multilocs sequence typing and agar dilution methods were used to define the genotype and antibiotic resistance of C. jejuni, respectively. Results In total, 126 C. jejuni strains were isolated. The prevalence of C. jejuni was 5.3% in diarrheal patients. The prevalence in poultry meat(36.5%) was higher than that in cattle meat(1.1%). However, the prevalence in poultry cloacal swabs(27.0%) was lower than that in cattle stool(57.3%). Sixty-two sequence types were obtained, among which 27 of the STs and 10 alleles were previously unreported. The most frequently observed clonal complexes were ST-21(11.9%), ST-22(10.3%), and ST-403(7.1%). ST-21, ST-45, ST-354, ST-403, and ST-443 complexes overlapped between isolates from patients and cattle, whereas ST-45 and ST-574 complexes overlapped between isolates from patients and poultry. All C. jejuni were resistant to at least one antibiotic. The highest resistance rate was toward ciprofloxacin(89.7%), followed by tetracycline(74.6%), and nalidixic acid(69.0%). Conclusion This is the first report of the genotypes and antibiotic resistance of C. jejuni in Shenzhen. Overlapping clonal complexes were found between isolates from patients and cattle, and between patients and poultry.

关键词： Campylobacter jejuni Multilocus sequence typing Antibiotic resistance Poultry Cattle Diarrheal patients

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Co-infections of SARS-CoV-2 with multiple common respiratory pathogens in infected patients

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Science China(Life Sciences) 2020年第4期63卷 606-609页

作者： Dachuan Lin Lei Liu Mingxia Zhang Yunlong Hu Qianting Yang Jiubiao Guo Yongchao Guo Youchao Dai Yuzhong Xu Yi Cai Xinchun Chen Zheng Zhang Kaisong Huang guangdong Provincial Key laboratory of Regional Immunity and Disease Department of Pathology BiologySchool of MedicineShenzhen UniversityShenzhen 518060China national Clinical Research Center for Infectious diseases Guangdong Key Lab for Diagnosis&Treatment of Emerging Infectious DiseasesShenzhen Third People’s HospitalSouthern University of Science and TechnologyShenzhen 518112China Department of Clinical laboratory Shenzhen Baoan HospitalThe Second Affiliated Hospital of Shenzhen UniversityShenzhen 518071China

Dear Editor,In late December 2019,an outbreak of severe pneumonia caused by an unknown etiological agent was initially reported in Wuhan,China,and then quickly spread throughout China and even abroad(Zhu et al.,2020).Swift control measures and etiological investigations were conducted by the Chinese government,physicians and researchers,and by using high throughput sequencing and virological testing,the mysterious pneumonia pathogen was shown to be a novel coronavirus(SARS-CoV-2)capable of person-to-person transmission(Zhu et al.,2020).Coronaviruses are a group of non-segmented,enveloped and positive-sense RNA viruses that belong to the subfamily of Coronavirinae in the family of Coronavirdiae and order of Nidovirales.

关键词： initially Swift envelope

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