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Strategies for reopening in the forthcoming COVID-19 era in China

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National Science Review 2022年第3期9卷 5-6页

作者： Wei-jie Guan Nan-shan Zhong state key laboratory of respiratory Disease National Clinical Research Center for Respiratory Disease Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University Guangzhou Medical University Department of Thoracic Surgery Guangzhou Institute for Respiratory Health The First Affiliated Hospital of Guangzhou Medical University Guangzhou Medical University Department of respiratory and Critical Care Medicine Foshan Second People's HospitalAffiliated Foshan Hospital of Southern Medical University

The transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the culprit pathogen of coronavirus disease 2019 (COVID-19), has resulted in more than 0.43 billion cases and 6 million deaths globally. Compared with other existing variants of concern, the Omicron variant is characterized by significantly greater infectivity (Ro≈6),greater tropism of the upper respiratory tract and lower severity of human infections [1].These characteristics of the Omicron variant are the basis upon which several developed countries are considering reopening.

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Initial COVID-19 severity influenced by SARS-CoV-2-specific T cells imprints T-cell memory and inversely affects reinfection

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2791-2803页

作者： Gang Yang Jinpeng Cao Jian Qin Xinyue Mei Shidong Deng Yingjiao Xia Jun Zhao Junxiang Wang Tao Luan Daxiang Chen Peiyu Huang Cheng Chen Xi Sun Qi Luo Jie Su Yunhui Zhang Nanshan Zhong Zhongfang Wang The Affiliated Hospital of Kunming University of Science and Technology.Department of respiratory and Critical Care Medicine The First People’s Hospital of Yunnan provinceKunmingYunnanChina Guangzhou National laboratory BiolandGuangzhouGuangdongChina state key laboratory of respiratory Disease&National Clinical Research Center for respiratory Disease Guangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Medical UniversityGuangzhouChina

The immunoprotective components control COVID-19 disease severity,as well as long-term adaptive immunity maintenance and subsequent reinfection risk discrepancies across initial COVID-19 severity,remain ***,we longitudinally analyzed SARS-CoV-2-specific immune effectors during the acute infection and convalescent phases of 165 patients with COVID-19 categorized by *** found that early and robust SARS-CoV-2-specific CD4^(+)and CD8^(+)T cell responses ameliorate disease progression and shortened hospital stay,while delayed and attenuated virus-specific CD8^(+)T cell responses are prominent severe COVID-19 *** antiviral antibody generation rather than titer level associates with severe ***,initial COVID-19 severity imprints the long-term maintenance of SARS-CoV-2-specific adaptive immunity,demonstrating that severe convalescents exhibited more sustained virus-specific antibodies and memory T cell responses compared to mild/moderate ***,initial COVID-19 severity inversely correlates with SARS-CoV-2 reinfection ***,our study unravels the complicated interaction between temporal characteristics of virus-specific T cell responses and COVID-19 severity to guide future SARS-CoV-2 wave management.

关键词： severity immunity infection

Dicoumarol is an effective post-exposure prophylactic for SARS-CoV-2 Omicron infection in human airway epithelium

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Signal Transduction and Targeted Therapy 2023年第7期8卷 3455-3465页

作者： Yang Peng Shi-ying Chen Zhao-ni Wang Zi-qing Zhou Jing Sun Gui-an Zhang Jia Li Lei Wang Jin-cun Zhao Xiao Xiao Tang De-Yun Wang Nan-shan Zhong state key laboratory of respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Medical UniversityGuangzhouGuangdongChina Department of Otolaryngology Infectious Diseases Translational Research ProgramYong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore Guangzhou laboratory GuangzhouChina

Repurposing existing drugs to inhibit SARS-CoV-2 infection in airway epithelial cells(AECs)is a quick way to find novel treatments for *** screening has found dicoumarol(DCM),a natural anticoagulant,to be a potential SARS-CoV-2 inhibitor,but its inhibitory effects and possible working mechanisms remain *** air-liquid interface culture of primary human AECs.

关键词： Omi infection epithelium

The stability of FKBP9 maintained by BiP is crucial for glioma progression

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Genes & Diseases 2024年第6期11卷 441-451页

作者： Shirong Li Wangxiao Xia Bin Sun Weiyan Peng Dong Yang Jing Gao Shuai He Hua Yang Yongjie Zhu Hu Zhou Tingxiu Xiang Qingpeng Kong Xudong Zhao Division of Abdominal Tumor Multimodality Treatment and laboratory of Animal Tumor Models Cancer Center and State Key Laboratory of Respiratory Health and Multimorbidity and Frontiers Science Center for Disease-related Molecular NetworkWest China HospitalSichuan UniversityChengduSichuan 610041China state key laboratory of Genetic Resources and Evolution/key laboratory of healthy Aging Research of Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China key laboratory of Molecular Oncology and Epigenetics The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Analyticali Chemistry and CAS key laboratory of Receptor Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China The Third People's Hospital of Yunnan Province KunmingYunnan 650600China

FK506-binding protein 9(FKBP9)is involved in tumor malignancy by resistance to endoplasmic reticulum(ER)stress,and the up-regulation of FKBP9 is associated with patients'poor *** current knowledge of the molecular mechanisms is still *** pre-vious study showed that FKBP9 could confer glioblastoma cell resistance to ER stress through ASK1-p38 ***,the upstream regulatory mechanism of FKBP9 expression is still *** this study,we identified the FKBP9 binding proteins using co-immunoprecipitation followed by mass *** showed that FKBP9 interacted with the binding immu-noglobulin protein(BiP).BiP bound directly to FKBP9 with high *** prolonged the half-life of the FKBP9 protein and stabilized the FKBP9 *** and FKBP9 protein levels were positively correlated in patients with glioma,and patients with high expression of BiP and FKBP9 showed a worse *** studies showed that FKBP9 knockout in genetically engineered mice inhibited intracranial glioblastoma formation and prolonged survival by decreasing cellular proliferation and ER stress-induced CHOP-related ***,normal cells may depend less on FKBP9,as shown by the absence of apoptosis upon FKBP9 knockdown in a non-transformed human cell line and overall normal development in homozygous knockout *** findings suggest an important role of BiP-regulated FKBP9-associated signaling in glioma progression and the BiP-FKBP9 axis may be a potential therapeutic target forglioma.

关键词： BiP Endoplasmic reticulum stress FKBP9 Glioma Knockout mice

RNA therapeutics:updates and future potential

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Science China(Life Sciences) 2023年第1期66卷 12-30页

作者： Caroline Zhang Biliang Zhang state key laboratory of respiratory Disease Guangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China Guangzhou RiboBio Co. LtdGuangzhou 510663China Argorna Pharmaceuticals Co. Guangzhou 510530China

Recent advancements in the production,modification,and cellular delivery of RNA molecules facilitated the expansion of RNAbased *** increasing understanding of RNA biology initiated a corresponding growth in RNA *** this review,the general concepts of five classes of RNA-based therapeutics,including RNA interference-based therapies,antisense oligonucleotides,small activating RNA therapies,circular RNA therapies,and messenger RNA-based therapeutics,will be ***,we also provide an overview of RNA-based therapeutics that have already received regulatory approval or are currently being evaluated in clinical trials,along with challenges faced by these ***-based drugs demonstrated positive clinical trial results and have the ability to address previously“undruggable”targets,which delivers great promise as a disruptive therapeutic technology to fulfill its full clinical potentiality.

关键词： RNA RNA therapeutics mRNA vaccine RNAi

SARS-CoV-2-specific CD4^(+)T cells are associated with long-term persistence of neutralizing antibodies

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Signal Transduction and Targeted Therapy 2022年第5期7卷 1773-1782页

作者： Zhongfang Wang Xiaoyun Yang Xinyue Mei Yumin Zhou Zhiqiang Tang Guichang Li Jiaying Zhong Mengqiu Yu Mingzhu Huang Xiaoling Su Bijia Lin Pengxing Cao Ji Yang Pixin Ran state key laboratory of respiratory Disease&National Clinical Research Center for respiratory Disease Guangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Medical UniversityGuangzhouChina The Second People’s Hospital of Changde HunanChina School of mathematics and Statistics University of MelbourneMelbourneVICAustralia

Understanding the decay and maintenance of long-term SARS-CoV-2 neutralizing antibodies in infected or vaccinated people and how vaccines protect against other SARS-CoV-2 variants is critical for assessing public vaccination ***,we measured different plasm antibody levels 2 and 12 months after disease onset,including anti-RBD,anti-N,total neutralizing antibodies,and two neutralizing-antibody *** found that total neutralizing antibodies declined more slowly than total anti-RBD and anti-N IgG.

关键词： antibodies neutral assessing

Effectiveness and mechanisms of sodium-dependent glucose transporter 2 inhibitors in type 2 diabetes and heart failure patients

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World Journal of Cardiology 2024年第10期16卷 611-615页

作者： Yan-Xi Zhang Hai-Sheng Hu Bao-Qing Sun Department of Clinical laboratory The First Affiliated Hospital of Guangzhou Medical UniversityState Key Laboratory of Respiratory DiseaseNational Center for Respiratory MedicineNational Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory HealthGuangzhou 510120Guangdong ProvinceChina

We comment on an article by GrubićRotkvićet al published in the recent issue of the World Journal of *** specifically focused on possible factors affecting the therapeutic effectiveness of sodium-dependent glucose transporter inhibitors(SGLT2i)in patients with type 2 diabetes mellitus(T2DM)and their impact on ***2i inhibits SGLT2 in the proximal tubules of the kidneys,lowering blood glucose levels by inhibiting glucose reabsorption by the kidneys and causing excess glucose to be excreted in the *** studies have demonstrated a role of SGLT2i in cardiovascular function in patients with diabetes who take metformin but still have poor glycemic *** addition,SGLT2i has been shown to be effective in anti-apoptosis,weight loss,and cardiovascular ***,it is feasible to treat patients with T2DM with cardiovascular or renal diseases using SGLT2i.

关键词： Sodium-dependent glucose transporter inhibitors Type 2 diabetes mellitus Heart failure Treatment Cardiovascular disease

Neural progenitor cells from human induced pluripotent stem cells generated less autogenous immune response

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Science China(Life Sciences) 2014年第2期57卷 162-170页

作者： HUANG Ke LIU PengFei LI Xiang CHEN ShuBin WANG LiHui QIN Li SU ZhengHui HUANG WenHao LIU JuLi JIA Bei LIU Jie CAI JingLei PEI DuanQing PAN GuangJin key laboratory of Regenerative Biology Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine Guangzhou Institutes of Biomedicine and HealthChinese Academy of Sciences Department of Regeneration Medicine School of Pharmaceutical Science Jilin University laboratory of Pathogen Biology State Key Laboratory of Respiratory Disease Department of Obstetrics and Gynecology Nanfang Hospital Southern Medical University

The breakthrough development of induced pluripotent stem cells(iPSCs)raises the prospect of patient-specific treatment for many diseases through the replacement of affected ***,whether iPSC-derived functional cell lineages generate a deleterious immune response upon auto-transplantation remains *** this study,we differentiated five human iPSC lines from skin fibroblasts and urine cells into neural progenitor cells(NPCs)and analyzed their *** co-culture with autogenous peripheral blood mononuclear cells(PBMCs),we showed that both somatic cells and iPSC-derived NPCs do not stimulate significant autogenous PBMC ***,a significant immune reaction was detected when these cells were co-cultured with allogenous ***,no significant expression of perforin or granzyme B was detected following stimulation of autogenous immune effector cells(CD3+CD8 T cells,CD3+CD8+T cells or CD3 CD56+NK cells)by NPCs in both PBMC and T cell co-culture *** results suggest that human iPSC-derived NPCs may not initiate an immune response in autogenous transplants,and thus set a base for further preclinical evaluation of human iPSCs.

关键词： induced pluripotent stem cells immunogenicity iPSC-derived neural progenitor cells

Measures of insulin resistance and beta cell function before and after treatment of HCV infection

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Virologica Sinica 2024年第4期39卷 667-674页

作者： Jizheng Chen Pan Qiu Tingfeng Zhao Haowei Jiang Kebinur Tursun Sulaiman Ksimu Xinwen Chen Qian Wang state key laboratory of respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou510182China Jiangsu Province key Lab of Human Functional Genomics Department of Biochemistry and Molecular BiologyNanjing Medical UniversityNanjing210029China state key laboratory of Virology Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan430071China Guangzhou laboratory Guangzhou510005China The First Affiliated Hospital of Xinjiang Medical University Urumchi830054China

The association between chronic HCV infection and type 2 diabetes mellitus(T2DM)has been established;however,there is limited research onβ-cell function particularly in the pre-diabetic ***,we evaluated indices ofβ-cell function and insulin sensitivity across the spectrum from normal glucose tolerance to T2DMin individuals with and without chronic hepatitis C(CHC),and the effects of antiviral treatments on these variables.A total of 153 noncirrhotic,non-fibrotic CHC patients with a BMIstate-and oral glucose tolerance test(OGTT)-derived indexes were used to evaluateβ-cell function and insulin *** all subjects,19(13%)had T2DM and 21%exhibited pre-diabetes including 8%isolated impaired fasting glucose(IFG)and 13%combined IFG and impaired glucose tolerance(IGT).Early and total insulin secretion adjusted for the degree of insulin resistance were decreased in pre-diabetic CHC patients compared to HCVuninfected *** eradication through DAA or IFN/RBV therapy demonstrated positive impacts on insulin sensitivity andβ-cell function in CHC patients who achieved sustained virologic response(SVR),regardless of fasting or OGTT *** findings emphasize the role of HCV in the development ofβ-cell dysfunction,while also suggesting that viral eradication can improve insulin secretion,reverse insulin resistance,and ameliorate glycemic *** results have important implications for managing pre-diabetic CHC patients and could prevent diabetes-related clinical manifestations and complications.

关键词： Hepatitis C virus(HCV) Type 2 diabetes(T2DM) Beta cell(β-cell) Insulin secretion