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SARS-CoV-2 breakthrough infections following inactivated vaccine vaccination induce few neutralizing antibodies against the currently emerging Omicron XBB variants

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Virologica Sinica 2024年第1期39卷 173-176页

作者： Fan Shen Chun Liang Cui-Xian Yang Ying Lu An-Qi Li Ying Duan Mi Zhang c Ren-Rong Tian a Xing-Qi Dong Yong-Tang Zheng Wei Pang Key laboratory of Bioactive Peptides of Yunnan Province/Key laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesKunming Institute of ZoologyChinese Academy of SciencesKunming650223China University of Chinese Academy of Sciences Beijing100049China Yunnan Provincial Infectious Disease Hospital Kunming650399China Department of Pathogen Biology and Immunology Faculty of Basic Medical ScienceKunming Medical UniversityKunming650500China

Dear Editor,COVID-19 inactivated vaccines have been extensively administered inChina.However,the majority of the Chinese population has experiencedbreakthrough infections from SARS-CoV-2 ancestral,Delta or Omicronvariants over the past three years,particularly during the wave of Omicron BA.5 and BA.7 variants at the end of 2022(Zhu et al.,2023).Subsequently,new Omicron variants,such as BQ.1,BQ.1.1,XBB,XBB.1/XBB.1.9,and XBB.1.5/XBB.1.9.1,are emerging in China(Yueetal.,2023;Zhu et al.,2023).Therefore,it is an urgentneed and a publichealth imperative to assess the extent of the immunoprotection established in this population.

关键词： breakthrough neutral Omi

Obituary:Prof.Yun Zhang(1963-2023)-A scientist focused on toxins and their underlying mechanisms to decipher human diseases

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Zoological research 2024年第1期45卷 230-232页

作者： Wenhui Lee Ren Lai the Key laboratory of Bioactive Peptides of Yunnan Province Engineering Laboratory of Peptides of Chinese Academy of SciencesKIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesNational Resource Centre for Non-Human PrimatesKunming Primate Research CentreNational Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)Sino-African Joint Research CentreNew Cornerstone Science InstituteKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650107China

Prof.Yun Zhang was born on 9 July 1963 in Kunming,Yunnan,China,during a tumultuous period which he often referenced.Throughout his life,he harbored a steadfast belief in using knowledge to unravel the mysteries of human diseases.His educational journey was marked by frequent changes in schools due to his parents’occupational relocations.However,despite these challenges,he consistently displayed diligence and was admitted to the East China University of Science and Technology,Shanghai,after completing high school in 1980.He remained an active and loyal member of the School of Biotechnology at the university.

关键词： admitted harbor mechanisms

Anemoside B4 inhibits SARS-CoV-2 replication in vitro and in vivo

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Chinese Herbal Medicines 2024年第1期16卷 106-112页

作者： Mingyue Xiao Ronghua Luo Qinghua Liang Honglv Jiang Yanli Liu Guoqiang Xu Hongwei Gao Yongtang Zheng Qiongming Xu Shilin Yang College of Pharmaceutical Sciences Soochow UniversitySuzhou 215123China Key laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesKunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Jiangsu Key laboratory of Neuropsychiatric diseases and Jiangsu Key laboratory of Preventive and Translational Medicine for Geriatric diseases Soochow UniversitySuzhou 215123China College of Pharmacy Guangxi University of Chinese MedicineNanning 530000China

Objective: Anemoside B4(AB4), the most abundant triterpenoidal saponin isolated from Pulsatilla chinensis, inhibited influenza virus FM1 or Klebsiella pneumoniae-induced pneumonia. However, the anti-SARS-CoV-2 effect of AB4 has not been unraveled. Therefore, this study aimed to determine the antiviral activity and potential mechanism of AB4 in inhibiting human coronavirus SARS-CoV-2 in vivo and in vitro.Methods: The cytotoxicity of AB4 was evaluated using the Cell Counting Kit-8(CCK8) assay. SARS-CoV-2 infected HEK293T, HPAEpiC, and Vero E6 cells were used for in vitro assays. The antiviral effect of AB4 in vivo was evaluated by SARS-CoV-2-infected hACE2-IRES-luc transgenic mouse model. Furthermore,label-free quantitative proteomics and bioinformatic analysis were performed to explore the potential antiviral mechanism of action of AB4. Type Ⅰ IFN signaling-associated proteins were assessed using Western blotting or immumohistochemical staining.Results: The data showed that AB4 reduced the propagation of SARS-CoV-2 along with the decreased Nucleocapsid protein(N), Spike protein(S), and 3C-like protease(3CLpro) in HEK293T cells. In vivo antiviral activity data revealed that AB4 inhibited viral replication and relieved pneumonia in a SARS-CoV-2 infected mouse model. We further disclosed that the antiviral activity of AB4 was associated with the enhanced interferon(IFN)-β response via the activation of retinoic acid-inducible gene Ⅰ(RIG-1) like receptor(RLP) pathways. Additionally, label-free quantitative proteomic analyses discovered that 17 proteins were significantly altered by AB4 in the SARS-CoV-2 coronavirus infections cells. These proteins mainly clustered in RNA metabolism.Conclusion: Our results indicated that AB4 inhibited SARS-CoV-2 replication through the RLR pathways and moderated the RNA metabolism, suggesting that it would be a potential lead compound for the development of anti-SARS-CoV-2 drugs.

关键词： anemoside B4 interferon RNA metabolism quantitative proteomics SARS-CoV-2

Mast cell degranulation-triggered by SARS-CoV-2 induces tracheal-bronchial epithelial inflammation and injury

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Virologica Sinica 2024年第2期39卷 309-318页

作者： Jian-Bo Cao Shu-Tong Zhu Xiao-Shan Huang Xing-Yuan Wang Meng-Li Wu Xin Li Feng-Liang Liu Ling Chen Yong-Tang Zheng Jian-Hua Wang Guangzhou Institutes of Biomedicine and Health Chinese Academy of SciencesGuangzhou 510530China School of Life Sciences and Medicine University of Science and Technology of ChinaHefei 230026China Key laboratory of Bioactive Peptides of Yunnan Province Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of SciencesKIZCUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesCenter for Biosafety Mega-ScienceKunming Institute of ZoologyChinese Academy of SciencesKunming 650223China University of Chinese Academy of Sciences Beijing 101408China

SARS-CoV-2 infection-induced hyper-inflammation is a key pathogenic factor of COVID-19.Our research,along with others',has demonstrated that mast cells(MCs)play a vital role in the initiation of hyper-inflammation caused by SARS-CoV-2.In previous study,we observed that SARS-CoV-2 infection induced the accumulation of MCs in the peri-bronchus and bronchioalveolar-duct junction in humanized mice.Additionally,we found that MC degranulation triggered by the spike protein resulted in inflammation in alveolar epithelial cells and capillary endothelial cells,leading to subsequent lung injury.The trachea and bronchus are the routes for SARS-CoV-2 transmission after virus inhalation,and inflammation in these regions could promote viral spread.MCs are widely distributed throughout the respiratory tract.Thus,in this study,we investigated the role of MCs and their degranulation in the development of inflammation in tracheal-bronchial epithelium.Histological analyses showed the accumulation and degranulation of MCs in the peri-trachea of humanized mice infected with SARS-CoV-2.MC degranulation caused lesions in trachea,and the formation of papillary hyperplasia was observed.Through transcriptome analysis in bronchial epithelial cells,we found that MC degranulation significantly altered multiple cellular signaling,particularly,leading to upregulated immune responses and inflammation.The administration of ebastine or loratadine effectively suppressed the induction of inflammatory factors in bronchial epithelial cells and alleviated tracheal injury in mice.Taken together,our findings confirm the essential role of MC degranulation in SARS-CoV-2-induced hyper-inflammation and the subsequent tissue lesions.Furthermore,our results support the use of ebastine or loratadine to inhibit SARS-CoV-2-triggered degranulation,thereby preventing tissue damage caused by hyper-inflammation.

关键词： SARS-CoV-2 Mast cell(MC) Bronchial epithelial cell Inflammation Tracheal injury

Identification of novel mammalian viruses in tree shrews(Tupaia belangeri chinensis)

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Zoological research 2024年第2期45卷 429-438页

作者： Hong Zhou Ren-Rong Tian Xiu-Rong Wang Jin-Xuan Yang Yun-Xiao Wang Ming-Liang Zhao Xu-Dong Zhang Yu-Hua Ma Long-Bao Lv Edward CHolmes Yong-Tang Zheng Wei-Feng Shi School of Clinical and Basic Medical Sciences Shandong First Medical University&Shandong Academy of Medical SciencesJi’nanShandong 250117China Key laboratory of Emerging Infectious diseases in Universities of Shandong Shandong First Medical University and Shandong Academy of Medical SciencesTaianShandong 271000China Key laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key laboratory of Bioactive Peptides of Yunnan Province KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesCenter for Biosafety Mega-ScienceKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China School of Public Health Shandong First Medical University&Shandong Academy of Medical SciencesJi’nanShandong 250117China National Resource Center for Non-Human Primates Kunming Primate Research CenterKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650107China Sydney Institute for Infectious diseases School of Medical SciencesThe University of SydneySydneyNew South Wales 2006Australia Department of Infectious diseases Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Shanghai Institute of Virology Shanghai Jiao Tong University School of MedicineShanghai 200025China

The Chinese tree shrew(Tupaia belangeri chinensis),a member of the mammalian order Scandentia,exhibits considerable similarities with primates,including humans,in aspects of its nervous,immune,and metabolic systems.These similarities have established the tree shrew as a promising experimental model for biomedical research on cancer,infectious diseases,metabolic disorders,and mental health conditions.Herein,we used metatranscriptomic sequencing to analyze plasma,as well as oral and anal swab samples,from 105 healthy asymptomatic tree shrews to identify the presence of potential zoonotic viruses.In total,eight mammalian viruses with complete genomes were identified,belonging to six viral families,including Flaviviridae,Hepeviridae,Parvovirinae,Picornaviridae,Sedoreoviridae,and Spinareoviridae.Notably,the presence of rotavirus was recorded in tree shrews for the first time.Three viruses-hepacivirus 1,parvovirus,and picornavirus-exhibited low genetic similarity(94%)to known viral strains.Phylogenetic analyses also revealed that the rotavirus and mammalian orthoreovirus identified in this study may be novel reassortants.These findings provide insights into the diverse viral spectrum present in captive Chinese tree shrews,highlighting the necessity for further research into their potential for crossspecies transmission.

关键词： Tree shrew(Tupaia belangeri chinensis) Meta-transcriptomic sequencing Mammalian viruses Genomic analysis

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Non-coding RNAs expression in SARS-CoV-2 infection:pathogenesis,clinical significance,and therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第1期9卷 55-78页

作者： Xiaoxing Liu Wandi Xiong Maosen Ye Tangsheng Lu Kai Yuan Suhua Chang Ying Han Yongxiang Wang Lin Lu Yanping Bao Peking University Sixth Hospital Peking University Institute of Mental HealthNHC Key Laboratory of Mental Health(Peking University)National Clinical Research Center for Mental Disorders(Peking University Sixth Hospital)100191 BeijingChina Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain research Peking University100871 BeijingChina Key laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan University570228 HaikouChina Key laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences&Yunnan Province KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesKunming Institute of ZoologyChinese Academy of Sciences650204 KunmingYunnanChina National Institute on Drug Dependence and Beijing Key laboratory of Drug Dependence Peking UniversityBeijing 100191China Institute of Brain Science and Brain-inspired research Shandong First Medical University&Shandong Academy of Medical Sciences250117 JinanShandongChina Department of Neurology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandongChina School of Public Health Peking University100191 BeijingChina

The coronavirus disease 2019(COVID-19)pandemic has been looming globally for three years,yet the diagnostic and treatment methods for COVID-19 are still undergoing extensive exploration,which holds paramount importance in mitigating future epidemics.Host non-coding RNAs(ncRNAs)display aberrations in the context of COVID-19.Specifically,microRNAs(miRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs)exhibit a close association with viral infection and disease progression.In this comprehensive review,an overview was presented of the expression profiles of host ncRNAs following SARS-CoV-2 invasion and of the potential functions in COVID-19 development,encompassing viral invasion,replication,immune response,and multiorgan deficits which include respiratory system,cardiac system,central nervous system,peripheral nervous system as well as long COVID.Furthermore,we provide an overview of several promising host ncRNA biomarkers for diverse clinical scenarios related to COVID-19,such as stratification biomarkers,prognostic biomarkers,and predictive biomarkers for treatment response.In addition,we also discuss the therapeutic potential of ncRNAs for COVID-19,presenting ncRNA-based strategies to facilitate the development of novel treatments.Through an in-depth analysis of the interplay between ncRNA and COVID-19 combined with our bioinformatic analysis,we hope to offer valuable insights into the stratification,prognosis,and treatment of COVID-19.

关键词： invasion therapeutic infection

REDH:A database of RNA editome in hematopoietic differentiation and malignancy

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Chinese Medical Journal 2024年第3期137卷 283-293页

作者： Jiayue Xu Jiahuan He Jiabin Yang Fengjiao Wang Yue Huo Yuehong Guo Yanmin Si Yufeng Gao Fang Wang Hui Cheng Tao Cheng Jia Yu Xiaoshuang Wang Yanni Ma State Key laboratory of common Mechanism research for Major diseases Haihe Laboratory of Cell EcosystemInstitute of Basic Medical SciencesChinese Academy of Medical SciencesBeijing 100005China Key laboratory of RNA and Hematopoietic Regulation Chinese Academy of Medical SciencesBeijing 100005China Department of Biochemistry and molecular Biology Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing 100005China State Key laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesInstitute of Hematology and Blood Diseases HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300020China Institute of Blood Transfusion Chinese Academy of Medical SciencesChengduSichuan 610052China

Background:The conversion of adenosine(A)to inosine(I)through deamination is the prevailing form of RNA editing,impacting numerous nuclear and cytoplasmic transcripts across various eukaryotic species.Millions of high-confidence RNA editing sites have been identified and integrated into various RNA databases,providing a convenient platform for the rapid identification of key drivers of cancer and potential therapeutic targets.However,the available database for integration of RNA editing in hematopoietic cells and hematopoietic malignancies is still lacking.Methods:We downloaded RNA sequencing(RNA-seq)data of 29 leukemia patients and 19 healthy donors from National Center for Biotechnology Information(NCBI)Gene Expression Omnibus(GEO)database,and RNA-seq data of 12 mouse hematopoietic cell populations obtained from our previous research were also used.We performed sequence alignment,identified RNA editing sites,and obtained characteristic editing sites related to normal hematopoietic development and abnormal editing sites associated with hematologic diseases.Results:We established a new database,"REDH",represents RNA editome in hematopoietic differentiation and malignancy.REDH is a curated database of associations between RNA editome and hematopoiesis.REDH integrates 30,796 editing sites from 12 murine adult hematopoietic cell populations and systematically characterizes more than 400,000 edited events in malignant hematopoietic samples from 48 cohorts(human).Through the Differentiation,Disease,Enrichment,and knowledge modules,each A-to-I editing site is systematically integrated,including its distribution throughout the genome,its clinical information(human sample),and functional editing sites under physiological and pathological conditions.Furthermore,REDH compares the similarities and differences of editing sites between different hematologic malignancies and healthy control.Conclusions:REDH is accessible at http://***/.This user-friendly database would aid in understanding the mechanisms of RNA editing in hema

关键词： RNA editing Hematopoietic differentiation Hematopoietic malignancy Database management systems

Jump further,leap higher,and consolidate stronger:A brief review of the long-term partnership between Kunming Institute of Zoology(kiz)and the Chinese University of Hong Kong(cuhk)in bioresources and molecular research

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Zoological research 2023年第3期44卷 556-558页

作者： Nelson Tang Yong-Tang Zheng Hui Zhao Wai-Yee Chan Yong-Gang Yao kiz-cuhk joint laboratory of bioresources and molecular research in common diseases The Chinese University of Hong KongHong Kong SARChina kiz-cuhk joint laboratory of bioresources and molecular research in common diseases Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650204China

The molecular etiologies of many prevalent diseases stem from genetic variations that arise during evolution and natural selection,as well as from environmental effects.The study of genetic diversity in human populations and analysis of molecular evolution in primates and other animal species can provide important insights regarding the pathogenesis of common diseases in both human and animal populations.

关键词： molecular evolution solid

Caloric restriction, Sirtuins, and cardiovascular diseases

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中华医学杂志(英文版) 2024年第8期137卷 2024 Mar 25页

作者： Wei Ziyu Yang Bo Wang Huiyu Lv Shuangjie Chen Houzao Liu Depei State Key laboratory of common Mechanism research for Major diseases Department of Biochemistry and molecular Biology Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100005 China

Caloric restriction (CR) is a well-established dietary intervention known to extend healthy lifespan and exert positive effects on aging-related diseases, including cardiovascular conditions. Sirtuins, a family of nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases, have emerged as key regulators of cellular metabolism, stress responses, and the aging process, serving as energy status sensors in response to CR. However, the mechanism through which CR regulates Sirtuin function to ameliorate cardiovascular disease remains unclear. This review not only provided an overview of recent research investigating the interplay between Sirtuins and CR, specifically focusing on their potential implications for cardiovascular health, but also provided a comprehensive summary of the benefits of CR for the cardiovascular system mediated directly via Sirtuins. CR has also been shown to have considerable impact on specific metabolic organs, leading to the production of small molecules that enter systemic circulation and subsequently regulate Sirtuin activity within the cardiovascular system. The direct and indirect effects of CR offer a potential mechanism for Sirtuin modulation and subsequent cardiovascular protection. Understanding the interplay between CR and Sirtuins will provide new insights for the development of interventions to prevent and treat cardiovascular diseases.

关键词： Caloric restriction Sirtuins Cardiovascular diseases Healthy lifestyle Dietary