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Single-cell Transcriptomic Analysis Reveals the Cellular Heterogeneity of Mesenchymal Stem Cells

Genomics, Proteomics & Bioinformatics 2022年第1期20卷 70-86页

作者： Chen zhang Xueshuai Han Jingkun liu {2. Chen Ying {2. Kunying Chen Jia Si Tian-yi Wang Hui Zhou Xiaoyun Zhao Xiaohui zhang Yihua An Yueying li Qian-Fei Wang CAS Key Laboratory of Genomic and Precision Medicine Collaborative Innovation Center of Genetics and DevelopmentBeijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China china National Center for Bioinformation Beijing 100101China university of Chinese Academy of Sciences Beijing 100049China department of Medical Experimental Center Qilu Hospital(Qingdao)Cheeloo College of MedicineShandong UniversityQingdao 266035China Qingdao Key Lab of Mitochondrial Medicine Qingdao 266035China International department Liangxiang CampusBeijing University of Chinese MedicineBeijing 102401China Yihua Biotechnology Co. Ltd.Beijing 100041China peking university People’s Hospital Peking University Institute of HematologyBeijing 100044China department of Functional Neurosurgery Third Medical CenterGeneral Hospital of Chinese PLABeijing 100039China

Ex vivo-expanded mesenchymal stem cells(MSCs)have been demonstrated to be a heterogeneous mixture of cells exhibiting varying proliferative,multipotential,and immunomodulatory ***,the exact characteristics of MSCs remain largely *** singlecell RNA sequencing of 61,2.6 MSCs derived from bone marrow and Wharton’s jelly,we revealed five distinct *** developmental trajectory of these five MSC subpopulations was mapped,revealing a differentiation path from stem-like active proliferative cells(APCs)to multipotent progenitor cells,followed by branching into two paths:1)unipotent preadipocytes or 2.bipotent prechondro-osteoblasts that were subsequently differentiated into unipotent *** stem-like APCs,expressing the perivascular mesodermal progenitor markers CSPG4.MCAM/NES,uniquely exhibited strong proliferation and stemness ***,the prechondrocyte subpopulation specifically expressed immunomodulatory genes and was able to suppress activated CD3^(+T) cell proliferation in vitro,supporting the role of this population in *** summary,our analysis mapped the heterogeneous subpopulations of MSCs and identified two subpopulations with potential functions in self-renewal and *** findings advance the definition of MSCs by identifying the specific functions of their heterogeneous cellular composition,allowing for more specific and effective MSC application through the purification of their functional subpopulations.

关键词： Mesenchymal stem cell Single-cell RNA sequencing Heterogeneity lineage trajectory Immune regulation

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Amplitude analysis of the decays D^(0)→π^(+)π^(−)π^(+)π^(−)and D^(0)→π^(+)π^(−)π^(0)π^(0)

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Chinese Physics C 2024年第8期48卷 6-33页

作者： M.Ablikim M.N.Achasov P.Adlarson O.Afedulidis X.C.Ai R.Aliberti A.Amoroso Q.An Y.Bai O.Bakina I.Balossino Y.Ban H.-R.Bao V.Batozskaya K.Begzsuren N.Berger M.Berlowski M.Bertani D.Bettoni F.Bianchi E.Bianco A.Bortone I.Boyko R.A.Briere A.Brueggemann H.Cai X.Cai A.Calcaterra G.F.Cao N.Cao S.A.Cetin J.F.Chang W.L.Chang G.R.Che G.Chelkov C.Chen C.H.Chen Chao Chen G.Chen H.S.Chen M.L.Chen S.J.Chen S.L.Chen S.M.Chen T.Chen X.R.Chen X.T.Chen Y.B.Chen Y.Q.Chen Z.J.Chen Z.Y.Chen S.K.Choi X.Chu G.Cibinetto F.Cossio J.J.Cui H.L.Dai J.P.Dai A.Dbeyssi R.E.de Boer D.Dedovich C.Q.Deng Z.Y.Deng A.Denig I.Denysenko M.Destefanis F.De Mori B.Fang S.S.Fang W.X.Fang Y.Fang Y.Q.Fang R.Farinelli L.Fava F.Feldbauer G.Felici C.Q.Feng J.H.Feng Y.T.Feng K.Fischer M.Fritsch C.D.Fu J.L.Fu Y.W.Fu H.Gao Y.N.Gao yang Gao S.Garbolino I.Garzia P.T.Ge Z.W.Ge C.Geng E.M.Gersabeck B.Ding X.X.Ding Y.Ding Y.Ding J.Dong L.Y.Dong M.Y.Dong X.Dong M.C.Du S.X.Du Z.H.Duan P.Egorov Y.H.Fan J.Fang JA.Gilman K.Goetzen L.Gong W.X.Gong W.Gradl S.Gramigna M.Greco M.H.Gu Y.T.Gu C.Y.Guan Z.L.Guan A.Q.Guo L.B.Guo M.J.Guo R.P.Guo Y.P.Guo A.Guskov J.Gutierrez K.L.Han T.T.Han X.Q.Hao F.A.Harris K.K.He K.L.He F.H.Heinsius C.H.Heinz Y.K.Heng C.Herold T.Holtmann P.C.Hong G.Y.Hou X.T.Hou Y.R.Hou Z.L.Hou B.Y.Hu H.M.Hu J.F.Hu T.Hu Y.Hu G.S.Huang K.X.Huang L.Q.Huang X.T.Huang Y.P.Huang T.Hussain F.H\"olzken N.H\"usken N.in der Wiesche M.Irshad J.Jackson S.Janchiv J.H.Jeong Q.Ji Q.P.Ji W.Ji X.B.Ji X.L.Ji Y.Y.Ji X.Q.Jia Z.K.Jia D.Jiang H.B.Jiang P.C.Jiang S.S.Jiang T.J.Jiang X.S.Jiang Y.Jiang J.B.Jiao J.K.Jiao Z.Jiao S.Jin Y.Jin M.Q.Jing X.M.Jing T.Johansson S.Kabana N.Kalantar-Nayestanaki X.L.Kang X.S.Kang M.Kavatsyuk B.C.Ke V.Khachatryan A.Khoukaz R.Kiuchi O.B.Kolcu B.Kopf M.Kuessner X.Kui A.Kupsc W.K\"uhn J.J.Lane P.Larin L.Lavezzi T.T.lei Z.H.lei H.leithoff M.Lellmann T.Lenz C.li C.li C.H.li Cheng li D.M.li F.li G.li H.li H.B.li H.J.li H.N.li Hui li J.R.li J.S.li K.li L.J.li L.K.li lei li M.H.li P.R.li Q.M.li Q.X.li R.li S.X.li T.li W.D.li W.G.li X.li X.H.li X.L.li X.Y.li Y Institute of High Energy Physics Chinese Academy of SciencesBeijing 100049China Beihang university Beijing 100191China Bochum Ruhr-university D-44780 BochumGermany Budker Institute of Nuclear Physics SB RAS(BINP) Novosibirsk 630090Russia Carnegie Mellon university PittsburghPennsylvania 15213USA Central china Normal university Wuhan 430079China Central South university Changsha 410083China china Center of Advanced Science and Technology Beijing 100190China china university of Geosciences Wuhan 430074China Chung-Ang university Seoul06974Republic of Korea COMSATS university Islamabad Lahore CampusDefence RoadOff Raiwind Road54000 LahorePakistan Fudan university Shanghai 200433China GSI Helmholtzcentre for Heavy Ion Research GmbH D-64291 DarmstadtGermany Guangxi Normal university Guilin 541004China Guangxi university Nanning 530004China Hangzhou Normal university Hangzhou 310036China Hebei university Baoding 071002China Helmholtz Institute Mainz Staudinger Weg 18D-55099 MainzGermany Henan Normal university Xinxiang 453007China Henan university Kaifeng 475004China Henan university of Science and Technology Luoyang 471003China Henan university of Technology Zhengzhou 450001China Huangshan College Huangshan 245000China Hunan Normal university Changsha 410081China Hunan university Changsha 410082China Indian Institute of Technology Madras Chennai 600036India Indiana university BloomingtonIndiana 47405USA INFN Laboratori Nazionali di Frascati INFN Laboratori Nazionali di FrascatiI-00044FrascatiItaly INFN Laboratori Nazionali di Frascati INFN Sezione di PerugiaI-06100PerugiaItaly INFN Laboratori Nazionali di Frascati University of PerugiaI-06100PerugiaItaly INFN Sezione di Ferrara INFN Sezione di FerraraI-44122FerraraItaly INFN Sezione di Ferrara University of FerraraI-44122FerraraItaly Inner Mongolia university Hohhot 010021China Institute of Modern Physics Lanzhou 730000China Institute of Physics and Technology Peace Avenue 54BUlaanbaatar 13330Mongolia Instituto de A

Using e^(+)e^(−)annihilation data corresponding to an integrated luminosity of 2.93 fb^(−1)taken at the center-of-mass energy√s=3.773 GeV with the BESIII detector,a joint amplitude analysis is performed on the decays D^(0)→π^(+)π^(−)π^(+)π^(−)and D^(0)→π^(+)π^(−)π^(0)π^(0)(non-η).The fit fractions of individual components are obtained,and large interferences among the dominant components of the decays D^(0)→a_(1)(12.0)π,D^(0)→π(1300)π,D^(0)→ρ(770)ρ(770),and D^(0)→2.ππ)_(S)are observed in both *** the obtained amplitude model,the CP-even fractions of D^(0)→π^(+)π^(−)π^(+)π^(−)and D^(0)→π^(+)π^(−)π^(0)π^(0)(non-η)are determined to be(75.2.1.1_(stat).±1.5_(syst.))%and(68.9±1.5_(stat).±2.4.(syst.))%,*** branching fractions of D^(0)→π^(+)π^(−)π^(+)π^(−)and D^(0)→π^(+)π^(−)π^(0)π^(0)(non-η)are measured to be(0.688±0.010_(stat.)±0.010_(syst.))%and(0.951±0.02._(stat.)±0.02._(syst.))%,*** amplitude analysis provides an important model for the binning strategy in measuring the strong phase parameters of D^(0)→4.when used to determine the CKM angleγ(ϕ_(3))via the B^(−)→DK^(−)decay.

关键词： BESIII D^(0)meson decays amplitude analysis CP-even fraction

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基于白光中子源的^(197)Au中子辐射俘获截面测量及共振参数分析

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物理学报 2024年第7期73卷 104-113页

作者：罗淏天张奇玮栾广源王晓宇邹翀任杰阮锡超贺国珠鲍杰孙琪黄翰雄王朝辉吴鸿毅顾旻皓余滔解立坤陈永浩安琪白怀勇鲍煜曹平陈昊磊陈琪萍陈裕凯陈朕崔增琪樊瑞睿封常青高可庆韩长材韩子杰何泳成洪杨黄蔚玲黄锡汝季筱璐吉旭阳蒋伟江浩雨姜智杰敬罕涛康玲康明涛李波李超李嘉雯李论李强李晓李样刘荣刘树彬刘星言穆奇丽宁常军齐斌斌任智洲宋英鹏宋朝晖孙虹孙康孙晓阳孙志嘉谭志新唐洪庆唐靖宇唐新懿田斌斌王丽娇王鹏程王琦王涛峰文杰温中伟吴青彪吴晓光吴煊羊奕伟易晗于莉于永积张国辉张林浩张显鹏张玉亮张志永赵豫斌周路平周祖英朱丹阳朱科军朱鹏朱兴华中国原子能科学研究院核数据重点实验室北京102413 中国科学院高能物理研究所北京100049 散裂中子源科学中心东莞523803 核探测与核电子学国家重点实验室北京100049 中国科学技术大学近代物理系核探测与核电子学国家重点实验室合肥230026 北京大学物理学院核物理与核技术国家重点实验室北京100871 中国工程物理研究院核物理与化学研究所绵阳621900 西北核技术研究院西安710024 中国科学院大学北京100049 中国科学技术大学工程与应用物理系合肥230026 北京航空航天大学物理学院北京100083 华能山东石岛湾核电有限公司荣成264312

中子辐射俘获反应在反应堆运行、核装置设计及核天体物理研究中起重要的作用.4.BaF_(2.探测装置有着高时间分辨能力、低中子灵敏度、高探测效率等优点,适合开展中子辐射俘获反应截面数据的测量.中国原子能科学研究院核数据重点实验室... 详细信息

中子辐射俘获反应在反应堆运行、核装置设计及核天体物理研究中起重要的作用.4.BaF_(2.探测装置有着高时间分辨能力、低中子灵敏度、高探测效率等优点,适合开展中子辐射俘获反应截面数据的测量.中国原子能科学研究院核数据重点实验室建立了伽马全吸收装置(Gamma total absorption facility,GTAF),该装置用2.块六棱BaF_(2.晶体和12.五棱BaF_(2.晶体构成了外径2. cm,内径10 cm的球壳,覆盖了95.2.的立体角.利用GTAF在中国散裂中子源Back-n束线上,测量了197Au(n,γ)的反应截面数据.测量数据通过能量筛选、PSD方法、晶体多重性筛选进行了初步本底扣除,随后结合对^(nat)C及空样品的测量数据对本底进行了分析及扣除,获得了197Au俘获反应的产额,利用SAMMY程序拟合得到了^(197)Au在1—100 e V的共振能量、中子共振宽度和伽马共振宽度参数.实验测量结果与ENDF/B-VIII.0数据库符合良好,其共振参数存在一定差异,分析原因可能与GTAF能量分辨率、Back-n的中子能谱测量精度、以及实验本底扣除方法相关,这也是下一步工作的重点.

关键词：中子辐射俘获截面共振参数白光中子源伽马全吸收装置

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青少年刷牙频率与血液指标的相关性:横断面观察性研究

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协和医学杂志 2024年第4期15卷 960-967页

作者：张旭杜函泽翟文昊宋帅华郭晓湲温琳琳黄蕾陈适李道伟潘慧吉林大学白求恩口腔医学院长春130021 中国医学科学院北京协和医院内分泌科国家卫生健康委内分泌重点实验室北京100730

目的分析青少年刷牙频率对血液指标的相关性,初步探讨刷牙频率对青少年全身健康的影响。方法采用便利抽样法,纳入济宁市第七中学2.2.级学生和济宁市体育训练中心体育训练学生为研究对象。采用单因素和多因素线性回归分析青少年刷牙频率... 详细信息

目的分析青少年刷牙频率对血液指标的相关性,初步探讨刷牙频率对青少年全身健康的影响。方法采用便利抽样法,纳入济宁市第七中学2.2.级学生和济宁市体育训练中心体育训练学生为研究对象。采用单因素和多因素线性回归分析青少年刷牙频率对嗜酸性粒细胞百分比(eosinophil percentage,EOS%)、嗜酸性粒细胞计数(eosinophil count,EOS#)、嗜碱性粒细胞百分比(basophil percentage,BAS%)、嗜碱性粒细胞计数(basophil count,BAS#)、过氧化物歧化酶(superoxide dismutase,SOD)、胰岛素样生长因子1(insulin-like growth factor 1,IGF-1)、尿酸(uric acid,UA)等血液指标的影响。结果共纳入305名青少年(济宁市第七中学167名、济宁市体育训练中心138名),其中男性192.(62.95%),女性113名(37.05%)。根据每日刷牙频率分为3组,分别为≤1次组(4..33%,12./305)、2.组(53.77%,164.305)和≥3次组(5.90%,18/305)。单因素线性回归分析显示,每日刷牙2.与EOS%、EOS#、BAS%和BAS#均呈显著负相关(β均0,P=0.02.,P=0.007);每日刷牙≥3次与UA呈显著负相关[β(95%CI):-0.16(-0.2.~0.04.,P=0.008]。多因素线性回归分析显示,每日刷牙2.与BAS%呈显著负相关(β4.0}、与SOD和IGF-1均呈显著正相关(β均>0,P=0.036,P=0.012.;每日刷牙≥3次与UA呈显著负相关(β2.)。亚组分析结果表明,男性青少年每日刷牙2.与IGF-1呈显著正相关(β>0,P=0.04.),女性青少年每日刷牙≥3次与UA呈显著负相关(β4.。结论青少年刷牙频率与多项影响全身健康的血液指标具有相关性,提示口腔健康与全身健康可能存在潜在关联。

关键词：刷牙频率血液指标全身健康口腔护理

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Passive Smoking During the Periconceptional Period and Risk for Neural Tube Defects in Offspring—Five Counties,Shanxi Province,china,2.10–2.16

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china CDC weekly 2021年第37期3卷 778-782页

作者： Yali zhang Jufen liu Le zhang {4. Jin Nicholas D E Greene Zhiwen li Aiguo Ren Institute of Reproductive and Child Health/Key Laboratory of Reproductive Health National Health Commission of the People’s Republic of ChinaPeking UniversityBeijingChina department of Epidemiology and Biostatistics School of Public HealthPeking UniversityBeijingChina UCL Great Ormond Street Institute of Child Health University College LondonLondonUK.

Summary What is already known about this topic?Passive smoking during pregnancy,which is prevalent in china,has been reported to be associated with an increased risk for neural tube defects(NTDs)in five counties of Shanxi Province in northern *** is added by this report?After 4.years since the implementation of the World Health Organization(WHO)Framework Convention on Tobacco Control(FCTC)in china.

关键词： china. Shanxi Period

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Growth differentiation factor 15 predicts cardiovascular events in stable coronary artery disease

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Journal of Geriatric Cardiology 2023年第7期20卷 527-537页

作者： Juan WANG li-Na HAN Dao-Sheng AI Xin-Yu WANG Wan-Jing zhang Xiao-Rong XU Hong-Bin liU Jing zhang Pan WANG Xu li Mu-lei CHEN Heart Center of beijing Chao-yang Hospital Capital Medical UniversityBeijing Key Laboratory of HypertensionBeijingChina department of Cardiology the Second Medical CenterNational Clinical Research Center for Geriatric DiseasesChinese PLA General HospitalBeijingChina Academy for Advanced Interdisciplinary Studies Peking University National Institute of Biological SciencesZhongguancun Life Science ParkTsinghua UniversityBeijingChina

BACKGROUND Growth differentiation factor 15(GDF-15)has been explored as a potential biomarker for various inflammatory diseases and cardiovascular *** study aimed to assess the predictive role of GDF-15 levels in cardiovascular events and all-cause mortality,considering traditional risk factors and other *** A prospective study was conducted and 3699 patients with stable coronary artery disease(CAD)were enrolled into the *** GDF-15 levels were *** follow-up was 3.1 years during the *** analyzed clinical variables and several *** Cox regression analysis was performed to evaluate prognostic performance of GDF-15 levels in predicting myocardial infarction(MI),heart failure,stroke,cardiovascular death,and non-cardiovascular *** Baseline GDF-15 levels for 3699 patients were grouped by quartile(≤1153,1153-1888,1888-304.,>304. ng/L).Higher GDF-15 levels were associated with older age,male gender,history of hypertension,and elevated levels of N-terminal pro Btype natriuretic peptide(NT-pro BNP),soluble suppression of tumorigenesis-2.sST2.,and creatine(each with Plished risk factors and biomarkers in Cox proportional hazards models,a 1 standard deviation(SD)increase in GDF-15 was associated with elevated risk of clinical events[hazard ratio(HR)=2.18,95%confidence interval(CI):(1.52.3.11)],including:MI[HR=2.8395%CI:(1.03-7.74.],heart failure[HR=2.7195%CI:(1.18-6.2.)],cardiovascular and non-cardiovascular death[HR=2.4.,95%CI(1.4.-4.11)]during the median follow up of 3.1 *** Higher levels of GDF-15 consistently provides prognostic information for cardiovascular events and all cause death,independent of clinical risk factors and other ***-15 could be considered as a valuable addition to future risk prediction model in secondary prevention for predicting clinical events in patient with stable CAD.

关键词： cardiovascular elevated coronary

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Orofacial Clefts in High Prevalence Area of Birth Defects—Five Counties,Shanxi Province,china,2.00–2.2.

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china CDC weekly 2021年第37期3卷 773-777页

作者： Jufen liu Yali {2. Le {2. linlin Wang lei Jin Nicholas D E Greene Zhiwen li Aiguo Ren Institute of Reproductive and Child Health/Key Laboratory of Reproductive Health National Health Commission of the People’s Republic of ChinaPeking UniversityBeijingChina department of Epidemiology and Biostatistics School of Public HealthPeking UniversityBeijingChina UCL Great Ormond Street Institute of Child Health University College LondonLondonUK.

Summary What is already known on this topic?The prevalence of structural birth defects,especially neural tube defects,decreased after national folic acid(FA)supplementation *** is added by this report?The prevalence of orofacial clefts(OFCs)in five counties of Shanxi Province in northern china,including most subtypes except cleft palate,showed a downward trend in the past two *** this study,pre-perinatal prevalence increased due to earlier detection.

关键词： Shanxi defects downward

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SUMOylation-triggered AliX activation modulates extracellular vesicles circTLCD4.RWDD3 to promote lymphatic metastasis of non-small cell lung cancer

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Signal Transduction and Targeted Therapy 2023年第12期8卷 5887-5903页

作者： Xiayao Diao Chao Guo Hanhao Zheng Ke Zhao Yuming Luo Mingjie An Yan lin Jiancheng Chen Yuanlong li Yuting li Xuehan Gao Jiaqi zhang Mengxin Zhou Wenliang Bai lei liu Guige Wang Lanjun zhang Xiaotian He Rusi zhang Zhihua li Changhao Chen Shanqing li department of Thoracic Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP.R.China department of Urology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouGuangdongP.R.China Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Sun Yat-sen Memorial HospitalState Key Laboratory of Oncology in South ChinaGuangzhouGuangdongP.R.China department of General Surgery Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhouGuangdongP.R.China Cancer Center Renmin Hospital of Wuhan UniversityWuhanHubeiP.R.China department of Thoracic Surgery Sun Yat-sen University Cancer CenterSun Yat-sen UniversityGuangzhouGuangdongP.R.China department of Medical Oncology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouGuangdongP.R.China

Lymph node(LN)metastasis is one of the predominant metastatic routes of non-small cell lung cancer(NSCLC)and is considered as a leading cause for the unsatisfactory prognosis of *** lymphangiogenesis is well-recognized as a crucial process in mediating LN metastasis,the regulatory mechanism involving lymphangiogenesis and LN metastasis in NSCLC remains *** this study,we employed high-throughput sequencing to identify a novel circular RNA(circRNA),circTLCD4.RWDD3,which was significantly upregulated in extracellular vesicles(EVs)from LN metastatic NSCLC and was positively associated with deteriorated OS and DFS of patients with NSCLC from multicenter clinical *** the expression of EV-packaged circTLCD4.RWDD3 inhibited lymphangiogenesis and LN metastasis of NSCLC both in vitro and in ***,circTLCD4.RWDD3 physically interacted with hnRNPA2.1 and mediated the SUMO2.modification at K108 residue of hnRNPA2.1 by upregulating ***,circTLCD4.RWDD3-induced SUMOylated hnRNPA2.1 was recognized by the SUMO interaction motif(SIM)of AliX and activated AliX to recruit ESCRT-III,thereby facilitating the sorting of circTLCD4.RWDD3 into NSCLC cell-derived ***,EV-packaged circTLCD4.RWDD3 was internalized by lymphatic endothelial cells to activate the transcription of PROX1,resulting in the lymphangiogenesis and LN metastasis of ***,blocking EV-mediated transmission of circTLCD4.RWDD3 via mutating SIM in AliX or K108 residue of hnRNPA2.1 inhibited the lymphangiogenesis and LN metastasis of NSCLC in *** findings reveal a precise mechanism underlying SUMOylated hnRNPA2.1-induced EV packaging of circTLCD4.RWDD3 in facilitating LN metastasis of NSCLC,suggesting that EV-packaged circTLCD4.RWDD3 could be a potential therapeutic target against LN metastatic NSCLC.

关键词： metastasis inhibited lymphatic

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Effect of human umbilical cord-derived mesenchymal stem cells on lung damage in severe COVID-19 patients:a randomized,double-blind,placebo-controlled phase 2.trial

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Signal Transduction and Targeted Therapy 2021年第3期6卷 888-896页

作者： lei Shi Hai Huang Xuechun Lu Xiaoyan Yan Xiaojing Jiang Ruonan Xu Siyu Wang Chao zhang Xin Yuan Zhe Xu lei Huang Jun-liang Fu Yuanyuan li Yu zhang Wei-Qi Yao Tianyi liu Jinwen Song liangliang Sun Fan yang Xin zhang Bo zhang Ming Shi Fanping Meng Yanning Song Yongpei Yu Jiqiu Wen Qi li Qing Mao Markus Maeurer Alimuddin Zumla Chen Yao Wei-Fen Xie Fu-Sheng Wang department of Infectious Diseases Fifth Medical Center of Chinese PLA General HospitalNational Clinical Research Center for Infectious DiseasesBeijingChina Wuhan Huoshenshan Hospital WuhanChina department of Respiratory Changzheng HospitalSecond Military Medical UniversityShanghaiChina Optical Valley Branch of Maternal and Child Hospital of Hubei Province WuhanChina department of Hematology Second Medical Center of Chinese PLA General HospitalBeijingChina peking university Clinical Research Institute Peking University First HospitalBeijingChina department of Infectious Disease General Hospital of Central Theater CommandWuhanChina VCANBIO Cell&Gene Engineering Corp. LtdTianjinChina National Industrial Base for Stem Cell Engineering Products TianjinChina department of Hematology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Key Laboratory of Cancer Center Fifth Medical Center of Chinese PLA General HospitalBeijingChina department of Endocrinology and Metabolism Changzheng HospitalSecond Military Medical UniversityShanghaiChina department of Radiology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Nursing department Fifth Medical Center of Chinese PLA General HospitalBeijingChina immunotherapy Programme Champalimaud Centre for the UnknownLisbonPortugal Med Clinic University of MainzMainzGermany Center for Clinical Microbiology Division of Infection and ImmunityUniversity College Londonand UCL Hospitals NIHR Biomedical Research CentreLondonUK department of Gastroenterology Changzheng HospitalSecond Military Medical UniversityShanghaiChina

Treatment of severe Coronavirus Disease 2.19(COVID-19)is *** performed a phase 2.trial to assess the efficacy andsafety of human umbilical cord-mesenchymal stem cells(UC-MScs)to treat severe coViD-19 patients with lung damage,based onour phase 1 *** this randomized,double-blind,and placebo-controlled trial,we recruited 101 severe coVID-19 patients withlung *** were randomly assigned at a 2.1 ratio to receive either UC-MSCs(4.10^(7)cells per infusion)or placebo on day 0,3,and *** primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day *** imagingoutcomes,6-minute walk test(6-MWT),maximum vital capacity,diffusing capacity,and adverse events were recorded and *** all,100 COVID-19 patients were finally received either UC-MSCs in=65)or placebo(n=35).UC-MSCs administrationexerted numerical improvement in whole lung lesion volume from baseline to day 2. compared with the placebo(the mediandifference was-13.31%,95%Cl-2..14.,2.13%,P=0.08).UC-MSCs significanty reduced the proportions of solid componentlesion volume compared with the placebo(median difference:-15.4.%;95%CI-30.82.,-0.39%;P=0.04.).The 6-MWT showedan increased distance in patients treated with UC-MSCs(difference:2..00 m;95%CI 0.00,57.00;P=0.057).The incidence of adverseevents was similar in the two *** results suggest that UC-MSCs treatment is a safe and potentially effective therapeuticapproach for COVID-19 patients with lung damage.A phase 3 trial is required to evaluate effects on reducing mortality andpreventing long-term pulmonary disability.

关键词： damage patients double

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Polycarcin V induces DNA-damage response and enables the profiling of DNA-binding proteins

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National Science Review 2022年第11期9卷 19-28页

作者： Zongwei Yue Fan Wu Fusheng Guo Jiyeong Park Jin Wang liyun zhang Daohong liao Wenyang li Orlando D.Sch?rer Xiaoguang lei beijing National Laboratory for Molecular Sciences Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of EducationDepartment of Chemical BiologyCollege of Chemistry and Molecular Engineering Synthetic and Functional Biomolecules CenterPeking University peking-Tsinghua Center for life Science Academy for Advanced Interdisciplinary Studies Peking University Center for Genomic Integrity Institute for Basic Science Jiangsu JITRI Molecular Engineering Inst.Co. Ltd. department of Biological Sciences School of Life Sciences Ulsan National Institute of Science and Technology Institute for Cancer Research Shenzhen Bay Laboratory

To maintain genomic integrity and avoid diseases, the DNA-damage response(DDR) not only detects and repairs DNA lesions, but also contributes to the resistance to DNA-damaging *** the DDR plays a significant role in drug discovery using the principle of synthetic lethality. The incomplete current knowledge of the DDR encouraged us to develop new strategies to identify and study its components and pathways. Polycarcin V, belonging to the C-aryl glycoside natural products, is a light-activatable DNA-intercalating agent that causes DNA damage by forming a covalent [2.2.cycloadduct with thymine residue under 365–4.0 nm of light irradiation in a DNA-sequence-independent manner. Taking advantage of the light-activatable feature and temporal control of DDR, we designed and synthesized polycarcin V-based bifunctional chemical probes, including one that cross-links DNA to DNA-binding protein to explore the DDR induced by polycarcin V and uncover novel DNA–protein interactions. Utilizing this chemical probe and activity-based protein profiling-stable isotope labeling with amino acids in cell culture, we identified 311 DNA-binding protein candidates, including known DDR factors and additional proteins that may be of interest in discovering new biology. We validated our approach by showing that our probe could specifically cross-link proteins involved in nucleotide excision repair(NER) that repair bulky DNA adducts. Our studies showed that the [2.2. cycloadduct formed by polycarcin V could indeed be repaired by NER in vivo. As a DNA-damaging agent, polycarcin V or its drug-like derivative plus blue light showed promising properties for psoriasis treatment, suggesting that it may itself hold promise for clinic applications.

关键词： polycarcin V [2.2. DNA photoadduct light-activatable chemical probe ABPP for DNA-binding protein proteomics psoriasis treatment

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