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NEDD8-conjugating enzyme UBC12 as a novel therapeutic target in esophageal squamous cell carcinoma

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1403-1406页

作者： shiwen wang Jingrong Xian Lihui Li Yanyu Jiang Yue Liu Lili Cai Robert M.Hoffman Lijun Jia Hu Zhao Yanmei Zhang Department of Laboratory Medicine Huadong Hospital Affiliated to Fudan UniversityShanghai 200040China Cancer Institute Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China Research Center on Aging and Medicine Fudan UniversityShanghai 200040China Shanghai Key Laboratory of Clinical Geriatric Medicine Shanghai 200040China Department of Surgery University of CaliforniaSan DiegoCAUSA

Dear Editor,Esophageal squamous cell carcinoma(ESCC)is the major histologic subtype of esophageal cancer with high incidence and mortality.1 However,few achievements have been made in the development of targeted drugs.2 Neddylation,a reversible post-translational modification,attaches ubiquitin-like molecule NEDD8 to substrates in a three-step enzymatic reaction catalyzed by NEDD8-activating enzyme E1(NAE,NAE1 and UBA3 heterodimer),NEDD8-conjugating enzyme E2s(UBE2M/UBC12 or UBE2F)and substrate-specific NEDD8-E3 ligases.3 The best-characterized substrates of neddylation are cullin family proteins,the essential components of multiunit Cullin-RING ubiquitin ligases(CRLs).4 Currently,the inhibition of cullin neddylation by targeting overactivated neddylation pathway has emerged as an attractive approach for anticancer therapy.5,6 Our previous study reported that MLN4924,a specific inhibitor of NAE,significantly inhibited the tumor growth of ESCC by blocking cullin neddylation and inactivating CRLs activity.7 However,recent studies found that MLN4924 treatment-emergent NAE mutations would confer the drug resistance.8,9 Therefore,it is urgent to identify other neddylation enzymes(E2s or E3s)as alternative anticancer targets and develop novel anti-ESCC strategies.

关键词： esophageal NEDD8 squamous

Journal of Geriatric Cardiology comes to press with a new look

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Journal of Geriatric Cardiology 2004年第2期1卷 69-70,76页

作者： shiwen wang MD,MCAE Editor-in-Chief Professor and Director of the Institute of Geriatric Cardiology Beijing,China Editor-in-Chief Professor and Director of the Institute of Geriatric Cardiology Beijing China

On behalf of all the editors and editorial board members, I would like to announce that the inaugural issue of the Journal of Geriatric Cardiology ( JGC ) was published after over two years of preparation, and the JGC will be continuously published. The JGC was born in accordance with the tough challenge of higher prevalence of cardiac diseases and/or complicated with other organ diseases in the elderly accompanied by the rapid growing number of the aged.

关键词： Journal of Geriatric Cardiology comes to press with a new look

Adversarial attacks and defenses for digital communication signals identification

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Digital Communications and Networks 2024年第3期10卷 756-764页

作者： Qiao Tian Sicheng Zhang shiwen Mao Yun Lin College of Computer Science and Technology Harbin Engineering UniversityHarbin150001China College of Information and Communication Engineering Harbin Engineering UniversityHarbin150000China Department of Electrical and Computer Engineering Auburn UniversityAuburnAL36849USA

As modern communication technology advances apace,the digital communication signals identification plays an important role in cognitive radio networks,the communication monitoring and management *** has become a promising solution to this problem due to its powerful modeling capability,which has become a consensus in academia and ***,because of the data-dependence and inexplicability of AI models and the openness of electromagnetic space,the physical layer digital communication signals identification model is threatened by adversarial *** examples pose a common threat to AI models,where well-designed and slight perturbations added to input data can cause wrong ***,the security of AI models for the digital communication signals identification is the premise of its efficient and credible *** this paper,we first launch adversarial attacks on the end-to-end AI model for automatic modulation classifi-cation,and then we explain and present three defense mechanisms based on the adversarial *** we present more detailed adversarial indicators to evaluate attack and defense ***,a demonstration verification system is developed to show that the adversarial attack is a real threat to the digital communication signals identification model,which should be paid more attention in future research.

关键词： Digital communication signals identification AI model Adversarial attacks Adversarial defenses Adversarial indicators

Animal model of non-bacterial multiple organ dysfunction syndrome in the elderly

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Journal of Geriatric Cardiology 2004年第1期1卷 58-64页

作者： Qinglei ZHU shiwen wang Jie YANG Tong YIN Xiaoshun QIAN Qiao XUE Bin XU Institute of Geriatric Cardiology Chinese PlA General HospitalBeijing 100853China Institute of Geriatric CardiologyChinese PlA General HospitalBeijing 100853China Institute of Geriatric CardiologyChinese PlA General HospitalBeijing 100853China Institute of Geriatric CardiologyChinese PlA General HospitalBeijing 100853China Institute of Geriatric CardiologyChinese PlA General HospitalBeijing 100853China Institute of Geriatric CardiologyChinese PlA General HospitalBeijing 100853China Institute of Geriatric CardiologyChinese PlA General HospitalBeijing 100853China

Objective To establish a model of multiple organ dysfunction syndrome in the elderly (MODSE) by intraperitoneal injection of different doses of zymosan, and to compare the multiple organ dysfunction syndrome (MODS) in adult and in the elderly rats. Methods Adult and senile rats, injected with different doses of zymosan intraperitoneally were examined for the changes in the function and morphology of the vital organs, including heart, liver, brain, lungs, and kidneys using blood gas and biochemistry analysis and histopathological examination methods. Results Compared with the normal controls of the adult and the elderly rats, the blood gas and blood biochemistry changed in different degrees in the different dosed zymosan groups. Pathological changes were also found in the vital organs including lungs, heart, liver, brain, kidneys, erc in the experimental groups. Under the same concentrations of zymosan, the reductions in respiratory, cardiac and renal functions in the senile groups were much more severe than those in the corresponding adult group. In the similar degree of model duplication, the senile rats had the tendency to die later than the adult rats. Conclusions Zymosan can be used in both elderly and adult rats to induce MODS model, and the best dosage for MODSE was ***/kg injected peritoneally. The model would hopefully be used in the study of mechanisms and the therapeutics on MODSE.

关键词： multiple organ dysfunction syndrome in the elderly animal model rat zymosan

Tropical Cyclone Monitoring and Analysis Techniques: A Review

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Journal of Meteorological Research 2024年第2期38卷 351-367页

作者： Chuanhai QIAN Ying LI Yinglong XU Xin wang Zenghai ZHANG Gaozhen NIE Da LIU shiwen ZHANG Institute for Development and Programme Design China Meteorological AdministrationBeijing 100081 Chinese Academy of Meteorological Sciences China Meteorological AdministrationBeijing 100081 National Meteorological Centre China Meteorological AdministrationBeijing 100081 National Satellite Meteorological Centre China Meteorological AdministrationBeijing 100081

Tropical cyclones(TCs),including tropical depressions and different categories of typhoons,hurricanes,and cyclonic storms,mostly originate over the oceans in the absence of direct ***,detailed monitoring and analysis of TCs has always been an unsolved *** the recent 20 years,great changes have taken place in domestic and foreign TC monitoring techniques,imposing a significant impact on TC operations and *** new technologies and products gradually emerge to support operations,with improved monitoring *** this paper,the progress on TC monitoring and analysis via meteorological satellites,radars,and airplanes in China and the world is reviewed,compared,and summarized,with special focuses on multisatellite fusion observations,in situ aircraft measurements,and some unconventional observation equipment such as rockets,saildrones,and underwater *** this basis,the paper points out future directions for improving TC monitoring and analysis in aid of better TC forecast and early warning.

关键词： tropical cyclone(TC) monitoring and analysis meteorological satellite aircraft reconnaissance

SNX11 Identified as an Essential Host Factor for SFTS Virus Infection by CRISPR Knockout Screening

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Virologica Sinica 2019年第5期34卷 508-520页

作者： Tiezhu Liu Jiajia Li Yang Liu Yuanyuan Qu Aqian Li Chuan Li Quanfu Zhang Wei Wu Jiandong Li Yan Liu Dexin Li shiwen wang Mifang Liang Key Laboratory of Medical Virology and Viral Diseases Ministry of Health of People's Republic of ChinaNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China CDC-WIV Joint Research Center for Emerging Diseases and Biosafety Wuhan 430071China Department of Microbiology Anhui Medical UniversityHefei 230032China The First Affiliated Hospital of Anhui Medical University Hefei 230022China

Severe fever with thrombocytopenia syndrome virus(SFTSV)is a highly pathogenic tick-borne bunyavirus that causes lethal infectious disease and severe fever with thrombocytopenia syndrome(SFTS)in *** molecular mechanisms and host cellular factors required for SFTSV infection remain *** a genome-wide CRISPR-based screening strategy,we identified a host cellular protein,sorting nexin 11(SNX11)which is involved in the intracellular endosomal trafficking pathway,as an essential cell factor for SFTSV *** SNX11-KO HeLa cell line was established,and SFTSV replication was significantly *** glycoproteins of SFTSV were detected and remained in later endosomal compartments but were not detectable in the endoplasmic reticulum(ER)or Golgi *** values in the endosomal compartments of the SNX11-KO cells increased compared with the pH of normal HeLa cells,and lysosomal-associated membrane protein 1(LAMP1)expression was significantly elevated in the SNX11-KO ***,these results indicated that penetration of SFTSV from the endolysosomes into the cytoplasm of host cells was blocked in the cells lacking *** study for the first time provides insight into the important role of the SNX11 as an essential host factor in the intracellular trafficking and penetrating process of SFTSV infection via potential regulation of viral protein sorting,membrane fusion,and other endocytic machinery.

关键词： CRISPR screen Severe fever with thrombocytopenia syndrome virus(SFTSV) Host factor Sorting nexin 11(SNX11)

Magnesium promotes vascularization and osseointegration in diabetic states

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International Journal of Oral Science 2024年第1期16卷 122-133页

作者： Linfeng Liu Feiyu wang Wei Song Danting Zhang Weimin Lin Qi Yin Qian wang Hanwen Li Quan Yuan shiwen Zhang State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases&West China Hospital of Stomatology Sichuan UniversityChengduChina State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases&Department of Oral Implantology West China Hospital of StomatologySichuan UniversityChengduChina

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral *** has been proved to promote bone healing under normal ***,we elucidate the mechanism by which Mg^(2+)promotes angiogenesis and osseointegration in diabetic *** generated a diabetic mice model and demonstrated thealveolar bone healing was compromised,with significantly decreased *** then developed Mg-coating implants with hydrothermal *** implants successfully improved the vascularization and osseointegration in diabetic ***,Mg^(2+)promoted the degradation of Kelch-like ECH-associated protein 1 (Keap1) and the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) by up-regulating the expression of sestrin 2 (SESN2) in endothelial cells,thus reducing theelevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under ***,our data suggested that Mg^(2+)promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondria metabolism.

关键词： healing diabetic impaired

Surveillance and Analysis of SARS-CoV-2 Variant Importation—China,January–June 2022

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China CDC weekly 2022年第50期4卷 1136-1142页

作者： Yenan Feng Xiang Zhao Zeyuan Yin Changcheng Wu Zhixiao Chen Kai Nie Ruhan A Lili Li Peihua Niu Ji wang Yuchao Wu shiwen wang Dayan wang Wenjie Tan Huanyu wang Xuejun Ma George FGao Cao Chen Wenbo Xu National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijingChina National Health Commission Key Laboratory for Medical Virology and Viral Diseases BeijingChina.

Introduction:The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron variant is the dominant circulating strain *** assess the importation of SARS-CoV-2 variants in the mainland of China during the Omicron epidemic,the genomic surveillance data of SARS-CoV-2 from imported coronavirus disease 2019(COVID-19)cases in the mainland of China during the first half of 2022 were ***:Sequences submitted from January to July 2022,with a collection date before June 30,2022,were *** proportions of SARS-CoV-2 variants as well as the relationships between the origin and destination of each Omicron imported case were ***:4,946 sequences of imported cases were submitted from 27 provincial-level administrative divisions(PLADs),and the median submission interval was within 1 month after *** 3,851 Omicron sequences with good quality,1 recombinant(XU)and 4 subvariants under monitoring(BA.4,BA.5,BA.2.12.1,and BA.2.13)were recorded,and 3 of them(BA.4,BA.5,and BA.2.12.1)caused local transmissions in the mainland of China later than that recorded in the *** subvariants dominated in the first half of 2022 and shifted from BA.1 to BA.2 then to BA.4 and *** percentage of BA.2 in the imported SARS-CoV-2 surveillance data was far higher than that in the Global Initiative on Sharing All Influenza Data(GISAID).The imported cases from Hong Kong Special Administrative Region,China,accounted for 32.30%of Omicron cases sampled,and 98.71%of them were ***:The Omicron variant showed the intra-Omicron evolution in the first half of 2022,and all of the Omicron subvariants were introduced into the mainland of China multiple times from multiple different locations.

关键词： mainland imported submitted

Nocturnal myocardial ischemic events and sleep-disordered breathing in patients with coronary artery disease

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Journal of Geriatric Cardiology 2004年第2期1卷 90-94页

作者： Wenli ZHANG shiwen wang Caiyi LU Peng LIU Rui CHEN Xian JI Yusheng ZHAO Institute of Geriatric Cardiology Chinese PLA General Hospital Beijing 100853 China

Objective To investigate the occurrence of nocturnal myocardial ischemia and its relationship with sleep-disordered breathing (apneas and oxygen desaturations) in patients with angina pectoris undergoing coronary *** Eighty-two men and 14 women referred for consideration of coronary intervention were randomly selected. Observation by an overnight sleep monitor and Holter recording were performed to study sleep-disordered breathing (oxyhemoglobin desaturations≥4% and apnea-hypopneas),heart rates, and ST-segment depressions (≥ 1mm, ≥1 min).Results Nocturnal ST-segment depressions occurred in 37 % of the patients. ST-segment depression within 2 min after an apnea-hypopnea or desaturation occurred in 17% of the patients. This temporal association was seen in 21% of the patients with nocturnal ST-segment depressions, more frequently in men (P<0.05) and more frequently in those with severe disordered breathing (P<0.05).Most of these ST-segment depressions were preceded by a series of breathing events: repeated apnea-hypopneas or desaturations or both in 73% of the patients. Conclusions Episodes of nocturnal myocardial ischemia are common in patients with angina pectoris. A temporal relationship between sleep-disordered breathing and myocardial ischemia was present in some of our patients, and occurs more frequently in men and in those with severely disordered breathing. (J Geriatr Cardiol 2004;1(2):90-94.)

关键词： angina pectoris myocardial ischemia coronary artery disease sleep-disordered breathing