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Einstein Probe discovery of EP240408a: A peculiar X-ray transient with an intermediate timescale

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 222-240页

作者： Wenda zhang Weimin Yuan Zhixing ling Yong Chen Nanda Rea Arne Rau Zhiming Cai Huaqing Cheng Francesco Coti Zelati lixin Dai jingwei Hu Shumei Jia Chichuan jin dongyue li Paul O’Brien Rongfeng Shen Xinwen Shu Shengli Sun Xiaojin Sun Xiaofeng Wang Lei Yang Bing zhang Chen zhang Shuang-Nan zhang Yonghe zhang Jie An David Buckley Alexis Coleiro Bertrand Cordier liming Dou Rob Eyles-Ferris Zhou Fan Hua Feng Shaoyu Fu Johan P.U.Fynbo Lluis Galbany Saurabh W.Jha Shuaiqing Jiang Albert Kong Erik Kuulkers Weihua Lei Wenxiong li Bifang liu Mingjun liu Xing liu Yuan liu Zhu liu Chandreyee maitra Alessio marino Itumeleng Monageng Kirpal Nandra Jeremy Sanders Roberto Soria lian Tao Junfeng Wang Song Wang Tinggui Wang Zhongxiang Wang Qingwen Wu Xuefeng Wu dong Xu Yanjun Xu Suijian Xue Yongquan Xue Zijian zhang Zipei Zhu Hu Zou Congying Bao Fansheng Chen Houlei Chen Tianxiang Chen Wei Chen Yehai Chen Yifan Chen Chenzhou Cui Weiwei Cui Yanfeng Dai dongwei Fan Ju Guan Dawei Han dongjie Hou Haibo Hu maohai Huang Jia Huo Zhenqing Jia Bowen Jiang Ge jin Chengkui li Junfei li Longhui li maoshun li Wei li Zhengda li Tianying lian Congzhan liu Heyang liu Huaqiu liu Fangjun Lu Laidan Luo Jia ma Xuan mao Haiwu Pan Xin Pan liming Song hui Sun Yunyin Tan Qingjun Tang Yihan Tao Hao Wang juan Wang Lei Wang Wenxin Wang Yilong Wang Yusa Wang Qinyu Wu Haitao Xu jingjing Xu Xinpeng Xu Yunfei Xu Zhao Xu Changbin Xue Yulong Xue Ailiang Yan Haonan Yang Xiongtao Yang Yanji Yang juan zhang Mo zhang Wenjie zhang Zhen zhang Zhen zhang Ziliang zhang donghua Zhao Haisheng Zhao Xiaofan Zhao Zijian Zhao Hongyan Zhou Yilin Zhou Yuxuan Zhu Zhencai Zhu National Astronomical Observatories Chinese Academy of Sciences School of Astronomy and Space Sciences University of Chinese Academy of Sciences Key Laboratory of Particle Astrophysics Institute of High Energy Physics Chinese Academy of Sciences Institute of Space Sciences (ICE) CSIC Institut d’Estudis Espacials de Catalunya (IEEC) max Planck Institute for Extraterrestrial Physics Innovation Academy for Microsatellites Chinese Academy of Sciences Department of Physics University of Hong Kong School of Physics and Astronomy University of Leicester School of Physics and Astronomy Sun Yat-sen University Department of Physics Anhui Normal University Shanghai Institute of Technical Physics Chinese Academy of Sciences Physics Department Tsinghua University Nevada Center for Astrophysics University of Nevada Las Vegas Department of Physics and Astronomy University of Nevada Las Vegas South African Astronomical Observatory Department of Astronomy University of Cape Town Department of Physics University of the Free State Université Paris Cité CNRS Astroparticule et Cosmologie Université Paris Cité CEA Paris-Saclay IRFU/DAp-AIM Department of Astronomy Guangzhou University Cosmic Dawn Center (DAWN) Niels Bohr Institute University of Copenhagen Department of Physics and Astronomy Rutgers the State University of New Jersey Institute for Cosmic Ray Research The University of Tokyo ESA/ESTEC Department of Astronomy School of Physics Huazhong University of Science and Technology INAF-Osservatorio Astrofisico di Torino Sydney Institute for Astronomy School of Physics The University of Sydney Department of Astronomy Xiamen University Institute for Frontiers in Astronomy and Astrophysics Beijing Normal University Department of Astronomy University of Science and Technology School of Astronomy and Space Sciences University of Science and Technology of China Institute of Deep Space Sciences Deep Space Exploration Laboratory Department of Astronomy School of Physics and Astronomy Yunnan University Shanghai Astronomical Observatory Chi

We report the discovery of a peculiar X-ray transient,EP240408a,by Einstein Probe （EP） and follow-up studies made with EP,Swift,NICER,GROND,ATCA and other ground-based multiwavelength *** new transient was first detected with Wide-field X-ray Telescope （WXT） on board EP on April 8th,2024,manifested in an intense yet brief X-ray flare lasting for *** flare reached a peak flux of 3.9×10-9erg cm-2s-1in 0.5-4 ke V,～300 times brighter than the underlying X-ray emission detected throughout the *** and more precise follow-up observations by EP/FXT,Swift and NICER confirmed the finding of this new *** X-ray spectrum is non-thermal in 0.5-10 ke V,with a power-law photon index varying *** X-ray light curve shows a plateau lasting for ～4 d,followed by a steep decay till becoming undetectable ～10 d after the initial *** on its temporal property and constraints from previous EP observations,an unusual timescale in the range of 7-23 d is found for EP240408a,which is intermediate between the commonly found fast and long-term *** counterparts have been found in optical and near-infrared,with the earliest observation at 17 h after the initial X-ray detection,suggestive of intrinsically weak emission in these *** demonstrate that the remarkable properties of EP240408a are inconsistent with any of the transient types known so far,by comparison with,in particular,jetted tidal disruption events,gamma-ray bursts,X-ray binaries and fast blue optical *** nature of EP240408a thus remains an *** suggest that EP240408a may represent a new type of transients with intermediate timescales of the order of～10 *** detection and follow-ups of more of such objects are essential for revealing their origin.

关键词： X-ray transients ${\bm~{Einstein~~Probe}}$

Numerical simulation study on multiphase flow pattern of hydrate slurry

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Petroleum Science 2023年第6期20卷 3897-3917页

作者： Xiao-Fang Lv Feng Chen Jie zhang Yang liu Qian-li ma hui Du chuan-Shuo Wang Shi-dong Zhou Bo-hui Shi Shang-Fei Song jing Gong Jiangsu Key Laboratory of Oil and Gas Storage&Transportation Technology Changzhou UniversityChangzhou213016JiangsuChina China Petroleum&Chemical Corporation Northwest Oilfield Branch Petroleum Engineering Technology Research InstituteUrumqi830011XinjiangChina Sinopec Shengli Oilﬁeld Company Dongying257001ShandongChina National Engineering Laboratory for Pipeline Safety/MOE Key Laboratory of Petroleum Engineering China University of Petroleum-Beijing102249BeijingChina

The research on the multiphase flow characteristics of hydrate slurry is the key to implementing the risk prevention and control technology of hydrate slurry in deep-water oil and gas mixed transportation *** paper established a geometric model based on the high-pressure hydrate slurry experimental *** model was used to carry out simulation research on the flow characteristics of gas-liquid-solid three-phase *** specific research is as follows:Firstly,the effects of factors such as slurry flow velocity,hydrate particle density,hydrate particle size,and hydrate volume fraction on the stratified smooth flow were specifically *** test obtained particle size has the most influence on the particle concentration *** slurry flow velocity is gradually increased based on stratified smooth *** flow patterns were observed and their characteristics were ***,increasing the slurry velocity to 2 m/s could achieve the slurry flow pattern of partial hydrate in the pipeline transition from stratified smooth flow to wavy *** the flow rate increases to 3 m/s,a violent wave forms throughout the entire *** on wave flow,as the velocity increased to 4 m/s,and the flow pattern changed to slug *** the particle concentration was below 10%,the increase of the concentration would aggravate the slug flow trend;if the particle concentration was above 10%,the increase of the concentration would weaken the slug flow trend,the increase of particle density and liquid viscosity would weaken the tendency of slug *** relationship between the pressure drop gradients of several different flow patterns is:slug flow>wave flow>stratified smooth flow.

关键词： Hydrate slurry Numerical simulation Multiphase flow Flow field distribution Flow pattern transition

Simulation study on cuttings transport of the backreaming operation for long horizontal section wells

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Petroleum Science 2024年第2期21卷 1149-1170页

作者： Yu-Fei Chen hui zhang Wen-Xin Wu Jun li Yong Ouyang Zong-Yu Lu De-Xin ma Yong-chuan Wu Jun-Bo liu Ke-Rou liu Zhuo-Xin dong China University of Petroleum(Beijing) Beijing102249China Beijing Normal University at Zhuhai Experimental and Practical Education Innovation CenterZhuhai519087GuangdongChina Oil&Gas Technology Research Institute of PetroChina Changqing Oilfield Company Xi'an710016ShaanxiChina PetroChina Xinjiang Oilfield Company Karamay834002XinjiangChina China Oilfield Services Ltd. Tianjin300459China

The backreaming operation plays a significant role in safe drilling for horizontal wellbores, while it may cause severe stuck pipe accidents. To lower the risk of the stuck pipe in backreaming operations, the mechanism of cuttings transport needs to be carefully investigated. In this research, a transient cuttings transport with multiple flow patterns model is developed to predict the evolution of cuttings transported in the annulus while backreaming. The established model can provide predictions of the distribution of cuttings bed along the wellbore considering the bulldozer effect caused by large-size drilling tools(LSDTs). The sensitivity analyses of the size of LSDTs, and backreaming operating parameters are conducted in Section 4. And a new theory is proposed to explain the mechanism of cuttings transport in the backreaming operation, in which both the bit and LSDTs have the “cleaning effect” and “plugging effect”.The results demonstrate that the cuttings bed in annuli is in a state of dynamic equilibrium, but the overall trend and the distribution pattern are obvious. First, larger diameters and longer drilling tools could lead to a higher risk of the stuck pipe. Second, we find that it is not the case that the higher flow rate is always better for hole cleaning, so three flow-rate intervals are discussed separately under the given conditions. When the “dangerous flow rate”(maller flow rate instead facilitates borehole cleaning. If the flow rate is large enough to be in the “high flow rate” interval(>35 L/s in Case 4),the higher the flow rate, the better the cleaning effect of cuttings beds. Third, an interval of tripping velocity called “dangerous velocity” is proposed, in which the cuttings bed accumulation near the LSDTs is more serious than

关键词： Backreaming Stuck pipe Hole cleaning Transient solid transport Multiple flow patterns

Expert panel’s guideline on cervicogenic headache:The Chinese Association for the Study of Pain recommendation

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World Journal of Clinical Cases 2021年第9期9卷 2027-2036页

作者： Hong Xiao Bao-Gan Peng Ke ma dong Huang Xian-Guo liu Yan Lv Qing liu li-juan Lu jin-Feng liu Yi-Mei li Tao Song Wei Tao Wen Shen Xiao-Qiu Yang lin Wang Xiao-Mei zhang Zhi-Gang Zhuang hui liu Yan-Qing liu Department of Algology West China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina Department of Orthopedics The Third Medical CenterGeneral Hospital of the Chinese People’s Liberation ArmyBeijing 100039China Department of Algology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Department of Algology The Third Xiangya Hospital of Central South UniversityChangsha 410013Hunan ProvinceChina Department of Physiology and Pain Research Center Sun Yat-Sen UniversityGuangzhou 510080Guangdong ProvinceChina Department of Algology Xijing HospitalAir Force Medical UniversityXi'an 710032Shaanxi ProvinceChina Department of Algology The Affiliated T.C.M Hospital of Southwest Medical UniversityLuzhou 646000Sichuan ProvinceChina Department of Algology Nanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008Jiangsu ProvinceChina Department of Algology The Second Affiliated Hospital of Harbin Medical UniversityHarbin 150001Heilongjiang ProvinceChina Department of Algology The First Affiliated Hospital of Xinjiang Medical UniversityUrumqi 830011XinjiangChina Department of Algology The First Affiliated Hospital of China Medical UniversityShenyang 110001Liaoning ProvinceChina Department of Neurosurgery Shenzhen University General HospitalShenzhen 518055Guangdong ProvinceChina Department of Algology The Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221002Jiangsu ProvinceChina Department of Algology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Algology The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550004Guizhou ProvinceChina Department of Algology The First Affiliated Hospital of Kunming Medical UniversityKunming 650032Yunnan ProvinceChina Department of Algology The Second Affiliated Hospital of Zhengzhou UniversityZhengzhou 450014Henan ProvinceChina Department of Algology Beijing Tiantan HospitalCapit

Cervicogenic headache(CEH)has been recognized as a unique category of headache that can be difficult to diagnose and *** China,CEH patients are managed by many different specialties,and the treatment plans remain ***,there is a great need for comprehensive evidence-based Chinese experts’recommendations for the management of *** Chinese Association for the Study of Pain asked an expert panel to develop recommendations for a series of questions that are essential for daily clinical management of patients with CEH.A group of multidisciplinary Chinese Association for the Study of Pain experts identified the clinically relevant topics in CEH.A systematic review of the literature was performed,and evidence supporting the benefits and harms for the management of CEH was ***-four recommendations were finally developed through expert consensus voting for evidence quality and recommendation *** hope this guideline provides direction for clinicians and patients making treatment decisions for the management of CEH.

关键词： Cervicogenic headache Expert recommendation Expert panel’s guideline Chinese Association for the Study of Pain Chronic pain

Metatranscriptome of human lung microbial communities in a cohort of mechanically ventilated COVID-19 Omicron patients

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Signal Transduction and Targeted Therapy 2023年第12期8卷 5919-5930页

作者： lin Wang Jia-Bao Cao Bin-Bin Xia Yue-juan li Xuan zhang Guo-Xin Mo Rui-juan Wang Si-Qi Guo Yu-Qing zhang Kun Xiao Guang-Fa Zhu Peng-Fei liu li-Cheng Song Xi-hui ma Ping-chao Xiang Jiang Wang Yu-Hong liu Fei Xie Xu-dong zhang Xiang-Xin li Wan-Lu Sun Yan Cao Kai-Fei Wang Wen-hui zhang Wei-chao Zhao Peng Yan Ji-chao Chen Yu-Wei Yang Zhong-Kuo Yu jing-Si Tang li Xiao Jie-Min Zhou li-Xin Xie Jun Wang College of Pulmonary&Critical Care Medicine 8th Medical Center of Chinese PLA General HospitalBeijing 100091China CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Faculty of Biological Science and Technology Baotou Teacher’s CollegeBaotou 014030China Department of Respiratory Medicine PLA Strategic Support Force Medical CenterBeijing 100101China Department of Respiratory and Critical Care Medicine Beijing Anzhen HospitalCapital Medical UniversityBeijing Institute of HeartLung and Blood Vessel DiseasesBeijing 100029China Respiratory Research Institute Department of Pulmonary&Critical Care MedicineBeijing Key Laboratory of OTIRthe 8th Medical Center of Chinese PLA General HospitalBeijing 100091China Shougang hospital of Peking University Beijing 100144China Department of Respiratory Medicine Beijing Changping HospitalBeijing 102200China Department of Respiratory and Critical Care Medicine Beijing Institute of Respiratory Medicine and Beijing Chao-Yang HospitalCapital Medical UniversityBeijing 100020China Pulmonary research institute Senior Department of Respiratory and Critical Care Medicinethe 8th medical center of Chinese PLA general hospitalBeijing 100091China College of Pulmonary&Critical Care Medicine Chinese PLA General HospitalBeijing 100853China China Aerospace Science&Industry Corporation 731 hospital Beijing 100074China Department of Respiratory and Critical Care Medicine Aerospace Center HospitalBeijing 100049China Vision Medicals Center for Infectious Diseases Guangzhou 510700China

The Omicron variant of the severe acute respiratory syndrome coronavirus 2(SARS‑CoV‑2)infected a substantial proportion of Chinese population,and understanding the factors underlying the severity of the disease and fatality is valuable for future prevention and clinical *** recruited 64 patients with invasive ventilation for COVID-19 and performed metatranscriptomic sequencing to profile host transcriptomic profiles,plus viral,bacterial,and fungal content,as well as virulence factors and examined their relationships to 28-day mortality were *** addition,the bronchoalveolar lavage fluid(BALF)samples from invasive ventilated hospital/community-acquired pneumonia patients(HAP/CAP)sampled in 2019 were included for *** analysis revealed that all Omicron strains belong to BA.5 and BF.7 sub-lineages,with no difference in 28-day mortality between *** to HAP/CAP cohort,invasive ventilated COVID-19 patients have distinct host transcriptomic and microbial signatures in the lower respiratory tract;and in the COVID-19 non-survivors,we found significantly lower gene expressions in pathways related viral processes and positive regulation of protein localization to plasma membrane,higher abundance of opportunistic pathogens including bacterial Alloprevotella,Caulobacter,Escherichia-Shigella,Ralstonia and fungal Aspergillus sydowii and Penicillium *** analysis further revealed significant associations between host immune responses and microbial compositions,besides synergy within viral,bacterial,and fungal *** study presents the relationships of lower respiratory tract microbiome and transcriptome in invasive ventilated COVID-19 patients,providing the basis for future clinical treatment and reduction of fatality.

关键词： patients mortality prevention

Genetic diversity center of cultivated soybean(Glycine max) in China——New insight and evidence for the diversity center of Chinese cultivated soybean

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Journal of Integrative Agriculture 2016年第11期15卷 2481-2487页

作者： WANG li-xia lin Fan-yun li lin-hai li Wei YAN Zhe LUAN Wei-jiang PIAO Ri-hua GUAN Yuan NING Xue-cheng ZHU li ma Yan-song dong Zhi-min zhang Hai-yan zhang Yue-qiang GUAN Rong-xia li ying-hui liu zhang-xiong CHANG Ru-zhen QIU li-juan The National Key Facility for Crop Gene Resources and Genetic Improvement (NFCRI)/Key Laboratory of Germplamsm Utilization Ministry of Agiculture/Institute of Crop SciencesChinese Academy of Agricultural Sciences College of Agriculture Northwest A & F University College of Agriculture Northeast Agricultural University College of Science and Technology Xinjiang Agricultural University Department of Agronomy Jilin Agricultural University Department of Agronomy Liaoning Agricultural University

Information on the center of genetic diversity of soybean（Glycine max） will be helpful not only for designing efficient strategies for breeding programs, but also for understanding the domestication and origin of this species. Here, we describe an analysis of genetic diversity based on simple-sequence repeat（SSR） variations within a core collection of 2 111 accessions of Chinese soybean landraces. Prior to the diversity assessment, the geographic origin of each accession was mapped. The map was then divided into grids each 2.5° in latitude and 5° in longitude. We found two regions that had higher number of alleles（NA） and greater polymorphic information content（PIC） values than the others. These regions are adjacently located within grid position of 30°–35°N×105°–110°E, which includes the valley of the middle and lower reaches of the Wei River, and the valley of the upper reaches of the Hanjiang River. It was also observed that in many regions, genetic diversity decreased with the increase in distance from the center. Another region, in northern Hebei Province（115°–120°E×40°–42.5°N）, was observed having higher diversity than any surrounding regions, indicating that this is a sub-center of soybean diversity. Based on the presented results, the domestication and origin of soybean are also discussed.

关键词： Glycine max genetic resources SSRs diversity center domestication

The In-Flight Realtime Trigger and Localization Software of GECAM

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Research in Astronomy and Astrophysics 2024年第10期24卷 11-24页

作者： Xiao-Yun Zhao Shao-lin Xiong Xiang-Yang Wen Xin-Qiao li Ce Cai Shuo Xiao Qi Luo Wen-Xi Peng dong-Ya Guo Zheng-Hua An Ke Gong jin-Yuan liao Yan-Qiu zhang Yue Huang Lu li Xing Wen Fei zhang jing Duan Chen-Wei Wang dong-li Shi Peng zhang Qi-Bin Yi chao-Yang li Yan-Bing Xu Xiao-Hua liang Ya-Qing liu Da-li zhang Xi-Lei Sun Fan zhang Gang Chen Huan-Yu Wang Sheng Yang Xiao-jing liu Min gao mao-Shun li jin-Zhou Wang Xing Zhou Yi Zhao Wang-Chen Xue chao Zheng Jia-Cong liu Xing-Bo Han jin-ling Qi Jia Huang Ke-Ke zhang Can Chen Xiong-Tao Yang dong-Jie Hou Yu-Sa Wang Rui Qiao Xiang ma Xiao-Bo li Ping Wang Xin-ying Song li-Ming Song Shi-Jie Zheng Bing li Hong-Mei zhang Yue Zhu Wei Chen Jian-Jian He Zhen zhang jin Hou Hong-Jun Wang Yan-chao Hao Xiang-Yu Wang Zong-Yuan Yang Zhi-Long Wen Zhi Chang Yuan-Yuan Du Rui gao Xiao-Fei Lan Yan-Guo li Gang li Xu-Fang li Fang-Jun Lu Hong Lu Bin Meng Feng Shi hui Wang hui-Zhen Wang Yu-Peng Xu Jia-Wei Yang Xue-juan Yang Shuang-Nan zhang chao-Yue zhang Cheng-Mo zhang Zhi-Cheng Tang Cheng Cheng Key Laboratory of Particle Astrophysics Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China University of Chinese Academy of Sciences Chinese Academy of SciencesBeijing 100049China School of Information Science and Technology Southwest Jiaotong UniversityChengdu 611756China Key Laboratory of Stellar and Interstellar Physics and Department of Physics Xiangtan UniversityXiangtan 411105China Physics and Space Science College China West Normal UniversityNanchong 637002China Department of Astronomy Beijing Normal UniversityBeijing 100875China Innovation Academy for Microsatellites of CAS Shanghai 201203China Changchun University of Science and Technology Changchun 130022China Chinese Academy of Sciences South America Center for Astronomy National Astronomical ObservatoriesCASBeijing 100101China

Realtime trigger and localization of bursts are the key functions of GECAM,an all-sky gamma-ray monitor launched on 2020 December *** developed a multifunctional trigger and localization software operating in the CPU of the GECAM Electronic *** onboard software has the following features:high trigger efficiency for real celestial bursts with a suppression of false triggers caused by charged particle bursts and background fluctuation,dedicated localization algorithm optimized for both short and long bursts,and low time latency of the trigger information which is downlinked through the Global Short Message Communication service of the global BeiDou navigation *** paper provides a detailed description of the design and development of the trigger and localization software system for *** covers the general design,workflow,the main functions,and the algorithms used in the *** paper also includes on-ground trigger tests using simulated gamma-ray bursts generated by a dedicated X-ray tube,as well as an overview of the performance for real celestial bursts during its in-orbit operation.

关键词： telescopes instrumentation:detectors methods:observational

Cell atlas of CCl_(4)-induced progressive liver fibrosis reveals stage-specific responses

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Zoological Research 2023年第3期44卷 451-466页

作者： Peng-Cheng Guo jing Zuo Ke-Ke Huang Guang-Yao Lai Xiao zhang juan An jin-Xiu li li li liang Wu Yi-Ting lin dong-Ye Wang Jiang-Shan Xu Shi-Jie Hao Yang Wang Rong-Hai li Wen ma Yu-Mo Song Chang liu chuan-Yu liu Zhen Dai Yan Xu Amar Deep Sharma Michael Ott Qing Ou-Yang Feng Huo Rong Fan Yong-Yin li jin-lin Hou Giacomo Volpe Long-Qi liu Miguel A.Esteban Yi-Wei Lai State Key Laboratory for Zoonotic Diseases Key Laboratory for Zoonosis Research of Ministry of EducationInstitute of ZoonosisCollege of Veterinary MedicineJilin UniversityChangchunJilin 130062China BGI-Hangzhou HangzhouZhejiang 310012China BGI-Shenzhen ShenzhenGuangdong 518083China Key Laboratory of Biological Targeting Diagnosis Therapy and Rehabilitation of Guangdong Higher Education InstitutesFifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong 510799China Laboratory of Integrative Biology Guangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouGuangdong 510530China Joint School of life Sciences Guangzhou Institutes of Biomedicine and Health and Guangzhou Medical UniversityGuangzhouGuangdong 510530China School of life Sciences Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230026China College of life Sciences University of Chinese Academy of SciencesBeijing 100049China Guangzhou Institutes of Biomedicine and Health Chinese Academy of SciencesGuangzhouGuangdong 510530China Biotherapy Centre Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China Department of Gastroenterology Hepatology and EndocrinologyHannover Medical SchoolHannover 30625Germany Department of Hepatobiliary Surgery and liver Transplant Center General Hospital of Southern Theater CommandGuangzhouGuangdong 510010China Department of Infectious Diseases Nanfang HospitalSouthern Medical UniversityGuangdong Provincial Key Laboratory of Viral Hepatitis ResearchGuangzhouGuangdong 510515China Hematology and Cell Therapy Unit IRCCS-Istituto Tumori‘Giovanni Paolo II’Bari 70124Italy Institute of Experimental Hematology Hannover Medical SchoolHannover 30625Germany

Chronic liver injury leads to progressive liver fibrosis and ultimately cirrhosis,a major cause of morbidity and mortality ***,there are currently no effective anti-fibrotic therapies available,especially for latestage patients,which is partly attributed to the major knowledge gap regarding liver cell heterogeneity and cellspecific responses in different fibrosis *** reveal the multicellular networks regulating mammalian liver fibrosis from mild to severe phenotypes,we generated a single-nucleus transcriptomic atlas encompassing 49919nuclei corresponding to all main liver cell types at different stages of murine carbon tetrachloride(CCl_(4))-induced progressive liver *** analysis distinguished the sequential responses to injury of hepatocytes,hepatic stellate cells and endothelial ***,we reconstructed the cell-cell interactions and gene regulatory networks implicated in these *** integrative analyses uncovered previously overlooked aspects of hepatocyte proliferation exhaustion and disrupted pericentral metabolic functions,dysfunction for clearance by apoptosis of activated hepatic stellate cells,accumulation of pro-fibrotic signals,and the switch from an anti-angiogenic to a pro-angiogenic program during CCl_(4)-induced progressive liver *** dataset thus constitutes a useful resource for understanding the molecular basis of progressive liver fibrosis using a relevant animal model.

关键词： liver fibrosis Toxicity Single-cell and single-nucleus RNA-sequencing Hepatocytes Hepatic stellate cells Angiogenesis Cell-cell interactions Gene regulatory networks

Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial

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Signal Transduction and Targeted Therapy 2021年第6期6卷 1845-1855页

作者： huijie Bian Zhao-hui Zheng Ding Wei Aidong Wen Zheng zhang Jian-Qi lian Wen-Zhen Kang Chun-Qiu Hao jing Wang Rong-Hua Xie Ke dong Jie-Lai Xia jin-lin Miao Wen Kang Guoquan li Di zhang Mingru zhang Xiu-Xuan Sun likun Ding Kui zhang Junfeng Jia jin Ding Zhiqin li Yanyan Jia lin-Na liu Zhe zhang Zhao-Wei gao Hong Du Na Yao Qing Wang Ke Wang Jie-Jie Geng Bin Wang Ting Guo Ruo Chen Yu-Meng Zhu li-juan Wang Qian He Rui-Rui Yao ying Shi Xiang-Min Yang Jian-Sheng Zhou Yi-Nan ma Ya-Tao Wang Xue liang Fei Huo Zhe Wang Yang zhang Xu Yang Ye zhang Lu-Hua gao ling Wang Xiao-Chun Chen Hao Tang Shuang-Shuang liu Qing-Yi Wang Zhi-Nan Chen Ping Zhu National Translational Science Center for Molecular Medicine and Department of Cell Biology Fourth Military Medical UniversityXi'anChina Department of Clinical Immunology Xijing HospitalFourth Military Medical UniversityXi'anChina Department of Pharmacy Xijing HospitalFourth Military Medical UniversityXi'anChina Center for Infectious Diseases Tangdu HospitalFourth Military Medical UniversityXi'anChina Department of Nuclear Medicine Xijing HospitalFourth Military Medical UniversityXi'anChina department of Clinical Diagnosis Tangdu HospitalFourth Military Medical UniversityXKanChina College of Military Preventive Medicine Fourth Military Medical UniversityXi'anChina Department of Pharmaceutics Tangdu HospitalFourth Military Medical UniversityXi'anChina Department of Pathology Fourth Military Medical UniversityXi'anChina Jiangsu Pacific Meinuoke Biopharmaceutical Co.Ltd ChangzhouChina Department of Foreign Languages Fourth Military Medical UniversityXi'anChina

Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)*** CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 *** is a humanized anti-CD147 IgG_(2) monoclonal antibody,which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019(COVID-19)***,we conducted a randomized,double-blinded,placebo-controlled phase 1 trial to evaluate the safety,tolerability,and pharmacokinetics of meplazumab in healthy subjects,and an open-labeled,concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 *** phase 1 study,59 subjects were enrolled and assigned to eight cohorts,and no serious treatment-emergent adverse event(TEAE)or TEAE grade≥3 was *** serum and peripheral blood Cmax and area under the curve showed non-linear pharmacokinetic *** obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each *** biodistribution study indicated that meplazumab reached lung tissue and maintained>14 days stable with the lung tissue/cardiac blood-pool ratio ranging from 0.41 to *** the exploratory phase 2 study,17 COVID-19 patients were enrolled,and 11 hospitalized patients were involved as concurrent *** meplazumab treatment significantly improved the discharged(P=0.005)and case severity(P=0.021),and reduced the time to virus negative(P=0.045)in comparison to the control *** results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.

关键词： patients dosage phase