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Multiomics approach reveals the ubiquitination-specific processes hijacked by SARS-CoV-2

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Signal Transduction and Targeted Therapy 2022年第10期7卷 3898-3910页

作者： Gang xu Yezi Wu Tongyang Xiao Furong Qi Lujie fan Shengyuan Zhang jian Zhou Yanhua He Xiang gao Hongxiang Zeng Yunfei Li zheng Zhang Institute for Hepatology National Clinical Research Center for Infectious DiseaseShenzhen Third People’s HospitalThe Second Affiliated HospitalSchool of MedicineSouthern University of Science and Technology518112 ShenzhenGuangdong ProvinceChina Guangzhou Laboratory Guangzhou Medical UniversityGuangzhouChina Department of Microbiology Second Military Medical UniversityShanghai Key Laboratory of Medical Biodefense200433 ShanghaiChina Guangdong Key laboratory for anti-infection Drug Quality Evaluation 518112 ShenzhenGuangdong ProvinceChina Shenzhen Research Center for Communicable Disease Diagnosis and Treatment of Chinese Academy of Medical Science ShenzhenGuangdong ProvinceChina

The Coronavirus Disease 2019(COVID-19)caused by Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2)is a global pandemic that seriously threatens health and socioeconomic development,but the existed antiviral drugs and vaccines still cannot yet halt the spread of the ***,a comprehensive and profound understanding of the pathogenesis of SARS-CoV-2 is urgently needed to explore effective therapeutic ***,we conducted a multiomics study of SARS-CoV-2-infected lung epithelial cells,including transcriptomic,proteomic,and *** analysis showed that SARS-CoV-2-infected lung epithelial cells activated strong innate immune response,including interferon and inflammatory *** further reveals the underlying mechanism of SARS-CoV-2 disrupting the host innate immune *** addition,SARS-CoV-2 proteins were found to be ubiquitinated during infection despite the fact that SARS-CoV-2 itself didn’t code any E3 ligase,and that ubiquitination at three sites on the Spike protein could significantly enhance viral *** screening of the E3 ubiquitin ligases and deubiquitinating enzymes(DUBs)library revealed four E3 ligases influencing SARS-CoV-2 infection,thus providing several new antiviral *** multiomics combined with high-throughput screening study reveals that SARS-CoV-2 not only modulates innate immunity,but also promotes viral infection,by hijacking ubiquitination-specific processes,highlighting potential antiviral and anti-inflammation targets.

关键词： ubiquitin immunity drugs

新一代含氟环保气体绿色制造标准体系建设实践与效果评价分析

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中国标准化 2024年第15期 161-167页

作者：徐铮颜光清罗霞李企真李霞李杰何高瑛郭雅飞张建君浙江省化工研究院有限公司中化蓝天氟材料有限公司东阳市巍华制冷材料有限公司浙江巨化技术中心有限公司

标准化工作对于推动新一代含氟环保气体产业高质量快速发展至关重要,在标准化工作开展时,积极推进标准体系有效实施、开展标准体系评价是必不可少的。本文以新一代含氟环保气体为例,探索了新一代含氟环保气体绿色制造标准体系实施与评... 详细信息

标准化工作对于推动新一代含氟环保气体产业高质量快速发展至关重要,在标准化工作开展时,积极推进标准体系有效实施、开展标准体系评价是必不可少的。本文以新一代含氟环保气体为例,探索了新一代含氟环保气体绿色制造标准体系实施与评价的方法,以期逐步建立完整的、适用于中国含氟环保气体产业的新一代含氟环保气体绿色制造标准体系和合适的实施方案及评价方法。

关键词：新一代含氟环保气体绿色制造标准体系实施评价

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基于网络药理学研究活血接骨胶囊治疗闭合性腰椎骨折的作用机制

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中国药物经济学 2024年第2期19卷 50-56页

作者：郑维宣范鸣翔伍英杰刘振洋罗建松许和贵贵州中医药大学贵阳550001

目的基于网络药理学探讨活血接骨胶囊治疗闭合性腰椎骨折的作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)、Uniprot等数据库并结合文献挖掘活血接骨胶囊的活性成分和作用靶点,运用OMIM、Genecards生物数据库筛选出闭合性... 详细信息

目的基于网络药理学探讨活血接骨胶囊治疗闭合性腰椎骨折的作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)、Uniprot等数据库并结合文献挖掘活血接骨胶囊的活性成分和作用靶点,运用OMIM、Genecards生物数据库筛选出闭合性腰椎骨折的相关靶点,将药物与疾病的作用靶点相互映射绘制韦恩图,筛选出交集靶点。将药物与疾病的交集靶点输入String数据库得到.tsv文件,导入cytoscape 3.8.2软件绘制蛋白质-蛋白质相互作用(PPI)网络,并计算拓扑参数筛选出核心靶点。将核心靶点导入David数据库进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)信号通路分析。结果筛选出活血接骨胶囊117个活性成分和654个潜在靶点,2 662个闭合性腰椎骨折疾病相关靶点,药物与疾病共有264个交集靶点。活血接骨胶囊可通过调节STAT3、JUN、MAPK1、NR3C1、FOS、HDAC1、MAPK14、SP1、RELA、TP53等核心靶点,干预TNF信号通路、TOLL样受体信号通路、AGE-RAGE通路、MAPK信号通路、IL-17通路、癌症通路、乙肝通路、Th17细胞等相关信号通路,从而达到治疗闭合性腰椎骨折的作用。结论该研究通过网络药理学方式预测了活血接骨胶囊治疗闭合性腰椎骨折的主要活性成分、靶点以及富集的通路,为其临床深入研究提供科学依据。

关键词：活性接骨胶囊闭合性腰椎骨折网络药理学作用机制

Identification of a novel coronavirus causing severe pneumonia in human:a descriptive study

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Chinese Medical Journal 2020年第9期133卷 1015-1024页

作者： Li-Li Ren Ye-Ming wang Zhi-Qiang Wu Zi-Chun Xiang Li guo Teng xu Yong-Zhong jiang Yan Xiong Yong-Jun Li Xing-wang Li Hui Li guo-Hui fan Xiao-Ying Gu Yan Xiao Hong gao Jiu-Yang xu fan Yang Xin-Ming wang Chao Wu Lan Chen Yi-Wei Liu Bo Liu jian Yang Xiao-Rui wang jie Dong Li Li Chao-Lin Huang jian-Ping Zhao Yi Hu Zhen-Shun Cheng Un-Lin Liu Zhao-Hui Qian Chuan Qin Qi Jin Bin Cao jian-Wei wang National Health Commission of the People’s Republic of China Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory Institute of Pathogen BiologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Department of Pulmonary and Critical Care Medicine Center of Respiratory MedicineNational Clinical Research Center for Respiratory DiseasesChina-Japan Friendship HospitalBeijing 100029China Institute of Respiratory Medicine Chinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100029China National Health Commission of the People’s Republic of China Key Laboratory of Systems Biology of Pathogens Institute of Pathogen BiologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Vision Medicals Co. LtdGuangzhouGuangdong 510000China Hubei Provincial Center for Disease Control and Prevention WuhanHubei 430079China Wuhan Center for Disease Control and Prevention WuhanHubei 430022China Clinical and Research Center of Infectious Diseases Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Institute of Clinical Medical Sciences China-Japan Friendship HospitalBeijing 100029China Institute of Laboratory Animal Science Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100021China Department of Basic Medical Sciences Tsinghua University School of MedicineBeijing 100084China Wuhan Jinyintan Hospital WuhanHubei 430022China Department of Pulmonary and Critical Care Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Sciences and TechnologyWuhanHubei 430030China Department of Pulmonary and Critical Care Medicine The Central Hospital of WuhanTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430014China Department of Respiratory Medicine Zhongnan Hospital of Wuhan UniversityWuhanHubei 430071China

Background:Human infections with zoonotic coronaviruses(CoVs),including severe acute respiratory syndrome(SARS)-CoV and Middle East respiratory syndrome(MERS)-CoV,have raised great public health concern ***,we report a novel batorigin CoV causing severe and fatal pneumonia in ***:We collected clinical data and bronchoalveolar lavage(BAL)specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital,Hubei province,*** acids of the BAL were extracted and subjected to next-generation *** isolation was carried out,and maximum-likelihood phylogenetic trees were ***:Five patients hospitalized from December 18 to December 29,2019 presented with fever,cough,and dyspnea accompanied by complications of acute respiratory distress *** radiography revealed diffuse opacities and *** of these patients *** results revealed the presence of a previously unknownβ-CoV strain in all five patients,with 99.8%to 99.9%nucleotide identities among the *** isolates showed 79.0%nucleotide identity with the sequence of SARS-CoV(GenBank NC_004718)and 51.8%identity with the sequence of MERS-CoV(GenBank NC_019843).The virus is phylogenetically closest to a bat SARS-like CoV(SL-ZC45,GenBank MG772933)with 87.6%to 87.7%nucleotide identity,but is in a separate ***,these viruses have a single intact open reading frame gene 8,as a further indicator of bat-origin ***,the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV,indicating that these viruses might use the same ***:A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

关键词： Bat-origin Coronavirus Zoonotic transmission Pneumonia Etiology Next-generation sequencing

Mechanisms exploration of Angelicae Sinensis Radix and Ligusticum Chuanxiong Rhizoma herb-pair for liver fibrosis prevention based on network pharmacology and experimental pharmacologylogy

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Chinese Journal of Natural Medicines 2021年第4期19卷 241-254页

作者： WU jian-Zhi LI Ya-Jing HUANG Guang-Rui xu Bing ZHOU Fei LIU Run-Ping gao Feng GE Jun-De CAI Ya-jie zheng Qi LI Xiao-Jiaoyang School of Life Sciences Beijing University of Chinese MedicineBeijing 100029China School of Chinese Materia Medica Beijing University of Chinese MedicineBeijing 100029China

Angelicae Sinensis Radix(Danggui)and Ligusticum Chuanxiong Rhizoma(Chuan Xiong)herb-pair(DC)have been frequently used in Traditional Chinese medicine(TCM)prescriptions for hundreds of years to prevent vascular diseases and alleviate ***,the mechanism of DC herb-pair in the prevention of liver fibrosis development was still *** the present study,the effects and mechanisms of DC herb-pair on liver fibrosis were examined using network pharmacology and mouse fibrotic *** on the network pharmacological analysis of 13 bioactive ingredients found in DC,a total of 46 targets and 71 pathways related to anti-fibrosis effects were obtained,which was associated with mitogen-activated protein kinase(MAPK)signal pathway,hepatic inflammation and fibrotic ***,this hypothesis was verified using carbon tetrachloride(CCl_4)-induced fibrosis *** of liver functional enzyme activities and histopathological examination showed that DC dramatically reduced bile acid levels,inflammatory cell infiltration and collagen deposition caused by CCl_*** increased expression of liver fibrosis markers,such as collagen 1,fibronectin,α-smooth muscle actin(α-SMA)and transforming growth factor-β(TGF-β),and inflammatory factors,such as chemokine(C-C motif)ligand 2(MCP-1),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and IL-6 in fibrotic mice were significantly downregulated by DC herb-pair through regulation of extracellular signal-regulated kinase 1/2(ERK1/2)-protein kinase B(AKT)signaling ***,these results suggest that DC prevents the development of liver fibrosis by inhibiting collagen deposition,decreasing inflammatory reactions and bile acid accumulation,which provides insights into the mechanisms of herbpair in improving liver fibrosis.

关键词： Angelicae Sinensis Radix Ligusticum Chuanxiong Rhizoma Liver fibrosis Herb-pair Network pharmacology

Lijiang 2.4-meter Telescope and its instruments

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Research in Astronomy and Astrophysics 2019年第10期19卷 95-108页

作者： Chuan-Jun wang Jin-Ming Bai Yu-Feng fan Ji-Rong Mao liang Chang Yu-Xin Xin Ju-Jia Zhang Bao-Li Lun jian-guo wang Xi-liang Zhang Mei Ying Kai-Xing Lu Xiao-Li wang Kai-fan Ji Ding-Rong Xiong Xiao-Guang Yu xu Ding Kai Ye Li-Feng Xing Wei-Min Yi liang xu Xiang-Ming zheng Yuan-jie Feng Shou-Sheng He xue-Li wang Zhong Liu Dong Chen Jun xu Song-Nian Qin Rui-Long Zhang Hui-Song Tan Zhi Li Ke Lou jian Li Wei-Wei Liu Yunnan Observatories Chinese Academy of SciencesKunming 650216China Key Laboratory for the Structure and Evolution of Celestial Objects Chinese Academy of Sciences Kunming 650216 China Center for Astronomical Mega-Science Chinese Academy of Sciences Beijing 100101 China University of Chinese Academy of Sciences Beijing 100049 China Astrophysics Center of Guangzhou University Guangzhou 510006China

The Lijiang 2.4-meter Telescope(LJT), the largest common-purpose optical telescope in China,has been available to the worldwide astronomical community since 2008. It is located at the gaomeigu site,Lijiang Observatory(LJO), in the southwest of China. The site has very good observational *** its 10-year operation, several instruments have been equipped on the LJT. Astronomers can perform both photometric and spectral observations. The main scientific goals of LJT include recording photometric and spectral evolution of supernovae, reverberation mapping of active galactic nuclei, investigating the physical properties of binary stars and near-earth objects(comets and asteroids), and identification of exoplanets and all kinds of transients. Until now, the masses of 41 high accretion rate black holes have been measured, and more than 168 supernovae have been identified by the LJT. More than 190 papers related to the LJT have been published. In this paper, the general observation conditions of the gaomeigu site is introduced at first. Then, the structure of the LJT is described in detail, including the optical, mechanical, motion and control system. The specification of all the instruments and some detailed parameters of the YFOSC is also presented. Finally, some important scientific results and future expectations are summarized.

关键词： telescopes Lijiang 2.4-m Telescope-instrumentation photometers-instrumentation spectrographs

Newborn emergency transport based on the fifth-generation wireless networks and blockchain

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World Journal of Pediatrics 2022年第7期18卷 520-524页

作者： Jin-Wu fang Wei-Jia Fu Rui Feng Hong-Tao Ni Yun Cao Cheng-jie Ye Ying Gu Xiao-Ling Ge fan Zhang Long-Quan jiang Juan-Wei Xing liang-Feng Tang Ying-Ying Zhang jian-guo Zhou Ru-Yi zheng Hong xu Xiao-Bo Zhang Department of Epidemiology School of Public HealthFudan UniversityShanghaiChina Children's Hospital of Fudan University ShanghaiChina Shanghai Key Laboratory of Intelligent Information.Processing School of Computer ScienceFudan UniversityShanghaiChina China Telecom(Shanghai)Co. LidShanghaiChina Department of Respiratory Children's Hospital of Fudan UniversityNo.399 Wanyuan RoadShanghai 201102China Department of Nephrology Children's Hospital of Fudan UniversityNo.399 Wanyuan RoadShanghai 201102China

Neonatal care is of great significance to health *** neonatal intensive care units(NICUs)started to be established in the late 1980s in China,neonatal mortal-ity has decreased each year to reach 3.4‰in 2020[1,2].However,the improvement for neonatal care is still on the *** than three-fifths of deaths included critically ill neonates occur in their first 28 days[3].Critically ill neo-nates usually have lower gestational age and body weight,leading to high mortality or requiring specific treatment and monitoring[4].It is a common practice to transfer a critically ill newborn patient to a tertiary children's hospi-tal with an excellent ***,it is crucial to pro-mote patients'safety by improving the neonatal transport network services[5].Owing to the complexity and rapid changes in neonatal conditions,especially for those requir-ing multi-disciplinary treatment,there is a high reliance on a specialized newborn transport team[6,7].

关键词： mortality transport treatment

EyeHealer:A large-scale anterior eye segment dataset with eye structure and lesion annotations

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Precision Clinical Medicine 2021年第2期4卷 85-92页

作者： Wenjia Cai jie xu Ke wang Xiaohong Liu Wenqin xu Huimin Cai Yuanxu gao Yuandong Su Meixia Zhang jie Zhu Charlotte L.Zhang Edward E.Zhang fangfei wang Yun Yin Iat fan Lai Guangyu wang Kang Zhang Yingfeng zheng State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhou 510060China Beijing Institute of Ophthalmology Capital Medical UniversityBeijing Tongren HospitalBeijing 100730China Department of Computer Science and Technology&BNRist Tsinghua UniversityBeijing 100084China Center for Biomedicine and Innovations Faculty of MedicineMacao University of Science and Technology and University HospitalMacao 999078China Guangzhou Women and Children’s Medical Center Guangzhou Medical UniversityGuangzhou 510623China Center for Translational Innovations West China Hospital and Sichuan UniversityChengdu 610041China Bioland Laboratory Guangzhou 510005China School of Business Macao University of Science and TechnologyMacao 999078China Ophthalmic Center Kiang Wu HospitalMacaoChina School of Information and Communication Engineering Beijing University of Posts and TelecommunicationsBeijing 100876China

Anterior segment eye diseases account for a significant proportion of presentations to eye clinics worldwide,including diseases associated with corneal pathologies,anterior chamber abnormalities(*** or inflammation),and lens *** construction of an automatic tool for segmentation of anterior segment eye lesions would greatly improve the efficiency of clinical *** research on artificial intelligence progressing in recent years,deep learning models have shown their superiority in image classification and *** training and evaluation of deep learning models should be based on a large amount of data annotated with expertise;however,such data are relatively scarce in the domain of ***,the authors developed a new medical image annotation system,called *** is a large-scale anterior eye segment dataset with both eye structures and lesions annotated at the pixel *** experiments were conducted to verify its performance in disease classification and eye lesion *** results showed that semantic segmentation models outperformed medical segmentation *** paper describes the establishment of the system for automated classification and segmentation *** dataset will be made publicly available to encourage future research in this area.

关键词： anterior segment eye diseases artificial intelligence annotation

Neuroprotectants attenuate hypobaric hypoxia-induced brain injuries in cynomolgus monkeys

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Zoological Research 2020年第1期41卷 3-19页

作者： Pei Zhang jie-Si Chen Qi-Ye Li Long-Xiang Sheng Yi-Xing gao Bing-zheng Lu Wen-Bo Zhu Xiao-Yu Zhan Yuan Li Zhi-Bing Yuan Gang xu Bi-Tao Qiu Min Yan Chun-xue guo You-Qiong wang Yi-Jun Huang Jing-Xia Zhang Fu-Yu Liu Zhong-Wei Tang Sui-Zhen Lin David NCooper Huan-Ming Yang jian wang Yu-Qi gao Wei Yin guo-jie Zhang Guang-Mei Yan State Key Laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China BGI-Shenzhen ShenzhenGuangdong 518083China Section for Ecology and Evolution Department of BiologyUniversity of CopenhagenCopenhagen DK-2100Denmark Department of Pharmacology Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhouGuangdong 510080China Institute of Medicine and Hygienic Equipment for High Altitude Region College of High Altitude Military MedicineThird Military Medical UniversityChongqing 400038China Key Laboratory of High Altitude Medicine of People's Liberation Army Chongqing 400038China Key Laboratory of High Altitude Environmental Medicine Third Military Medical UniversityMinistry of EducationChongqing 400038China School of Pharmaceutical Sciences Sun Yat-Sen UniversityGuangzhouGuangdong 510006China Guangzhou Cellprotek Pharmaceutical Co.Ltd. GuangzhouGuangdong 510663China Institute of Medical Genetics School of MedicineCardiff UniversityCardiff CF144XNUK James D.Watson Institute of Genome Sciences HangzhouZhejiang 310058China Department of Biochemistry Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhouGuangdong 510080China Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunmingYunnan 650223China China National Genebank BGI-ShenzhenShenzhenGuangdong 518120China

Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily using non-primate animal models that are genetically distant to humans, thus hindering the development of disease treatment. Here, we report that cynomolgus monkeys (Macaca fascicularis) exposed to acute HH developed human-like HH syndrome involving severe brain injury and abnormal behavior. Transcriptome profiling of white blood cells and brain tissue from monkeys exposed to increasing altitude revealed the central role of the HIF-1 and other novel signaling pathways, such as the vitamin D receptor (VDR) signaling pathway, in co-regulating HH-induced inflammation processes. We also observed profound transcriptomic alterations in brains after exposure to acute HH, including the activation of angiogenesis and impairment of aerobic respiration and protein folding processes, which likely underlie the pathological effects of HH-induced brain injury. Administration of progesterone (PROG) and steroid neuroprotectant 5α-androst-3β,5,6β-triol (TRIOL) significantly attenuated brain injuries and rescued the transcriptomic changes induced by acute HH. Functional investigation of the affected genes suggested that these two neuroprotectants protect the brain by targeting different pathways, with PROG enhancing erythropoiesis and TRIOL suppressing glutamate-induced excitotoxicity. Thus, this study advances our understanding of the pathology induced by acute HH and provides potential compounds for the development of neuroprotectant drugs for therapeutic treatment.

关键词： Acute hypobaric hypoxia Cynomolgus monkeys Brain injury Neuroprotectant Gene regulatory networks