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Identification of Nonstructural Protein 8 as the N-Terminus of the RNA-Dependent RNA Polymerase of Porcine Reproductive and respiratory Syndrome Virus

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Virologica Sinica 2018年第5期33卷 429-439页

作者： Yuanyuan Liu Yunhao Hu Yue Chai Liping Liu Jiangwei Song Shaochuan Zhou Jia Su Lei Zhou Xinna Ge Xin Guo Jun Han Hanchun Yang key laboratory of Animal Epidemiology of the Ministry of Agriculture College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology China Agricultural University

Porcine reproductive and respiratory syndrome virus (PRRSV) is a member within the family Arteriviridae of the order Nidovirales. Replication of this positive-stranded RNA virus within the host cell involves expression of viral replicase proteins encoded by two ORFs, namely ORF1 a and ORF1 b. In particular, translation of ORF1 b depends on a-1-ribosomal frameshift strategy. Thus, nonstructural protein 9 (nsp9), the first protein within ORF1 b that specifies the function of the viral RNA-dependent RNA polymerase, is expressed as the C-terminal extension of nsp8, a small nsp that is encoded by ORF1 a. However, it has remained unclear whether the mature form of nsp9 in virus-infected cells still retains nsp8,addressing which is clearly critical to understand the biological function of nsp9. By taking advantage of specific antibodies to both nsp8 and nsp9, we report the following findings. (1) In infected cells, PRRSV nsp9 was identified as a major product with a size between 72 and 95 k Da (72–95 KDa form), which exhibited the similar mobility on the gel to the in vitro expressed nsp8–9 ORF1 b, but not the ORF1 b-coded portion (nsp9 ORF1 b). (2) The antibodies to nsp8, but not to nsp7 or nsp10, could detect a major product that had the similar mobility to the 72–95 KDa form of nsp9. Moreover, nsp9 could be co-immunoprecipitated by antibodies to nsp8, and vice versa. (3) Neither nsp4 nor nsp2 PLP2 was able to cleave nsp8–nsp9 in vitro. Together, our studies provide experimental evidence to suggest that nsp8 is an N-terminal extension of *** findings here paves way for further charactering the biological function of PRRSV nsp9.

关键词： Porcine reproductive and respiratory syndrome virus (PRRSV) Nsp8 Nsp9

Nsp2 and GP5-M of Porcine Reproductive and respiratory Syndrome Virus Contribute to Targets for Neutralizing Antibodies

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Virologica Sinica 2019年第6期34卷 631-640页

作者： Jia Su Lei Zhou Bicheng He Xinhui Zhang Xinna Ge Jun Han Xin Guo Hanchun Yang key laboratory of Animal Epidemiology of the Ministry of Agriculture College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology China Agricultural University

Porcine reproductive and respiratory syndrome virus(PRRSV)is characterized by its genetic variation and limited cross protection among heterologous *** though several viral structural proteins have been regarded as inducers of neutralizing antibodies(NAs)against PRRSV,the mechanism underlying limited cross-neutralization among heterologous strains is still *** the present study,examinations of NA cross reaction between a highly pathogenic PRRSV(HP-PRRSV)strain,JXwn06,and a low pathogenic PRRSV(LP-PRRSV)strain,HB-1/3.9,were conducted with viral neutralization assays in MARC-145 *** of the JXwn06-hyperimmuned pigs’sera could neutralize HB-1/3.9 in vitro and vice *** address the genetic variation between these two viruses that are associated with limited crossneutralization,chimeric viruses with coding regions swapped between these two strains were *** neutralization assays indicated that variations in nonstructural protein 2(nsp2)and structural proteins together contribute to weak cross-neutralization activity between JXwn06 and HB-1/***,we substituted the nsp2-,glycoprotein2(GP2)-,GP3-,and GP4-coding regions together,or nsp2-,GP5-,and membrane(M)protein-coding regions simultaneously between these two viruses to construct chimeric viruses to test cross-neutralization reactivity with hyperimmunized sera induced by their parental *** results indicated that the swapped nsp2 and GP5-M viruses increased the neutralization reactivity with the donor strain antisera in MARC-145 *** together,these results show that variations in nsp2 and GP5-M correlate with the limited neutralization reactivity between the heterologous strains HP-PRRSV JXwn06 and LP-PRRSV HB-1/3.9.

关键词： Porcine reproductive and respiratory syndrome virus(PRRSV) Neutralizing antibody(NA) Non-structural protein 2(nsp2) Structural proteins(SPs)

Prognostic value of the RNA editing enzyme: ADAR1, and its association with immune cells infiltration in pancreatic adenocarcinoma

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Genes & Diseases 2023年第1期10卷 41-44页

作者： Jialong Qi You Zhou Zhikai Zhu Chuanshan Xu Wenjie Chen key laboratory of Molecular Target&Clinical Pharmacology and the state&NMPA key laboratory of respiratory Disease School of Pharmaceutical Sciences&the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhouGuangdong 511436China Yunnan Digestive Endoscopy Clinical Medical Center Department of GastroenterologyThe First People's Hospital of Yunnan ProvinceKunming 650032China Beijing Tiantan Hospital Capital Medical UniversityBeijing 100070China state key laboratory of respiratory Disease Guangdong-Hongkong-Macao Joint Laboratory of Respiratory Infectious DiseaseGuangzhouGuangdong 510182China Sydney Vital Translational Cancer Research Centre Westbourne StNSW 2065Australia

The adenosine deaminase acting on RNA(ADAR)protein family was well characterized as RNA editing enzymes converting adenosines to inosines(A-to-l)in dsRNA *** share a homologous structure including the dsRNA-binding domain and the deaminase ***1 function as the primary editing enzyme for A-to-l mutation because of its higher and ubiquitous expression compared to ADAR2 and ADAR3 in eukaryotes.

关键词： ADAR1 adenocarcinoma editing

Biomimetic carbon nanotubes for neurological disease therapeutics as inherent medication

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Acta Pharmaceutica Sinica B 2020年第2期10卷 239-248页

作者： Chenyang Xiang Yuxuan Zhang Weisheng Guo Xing-Jie Liang Translational Medicine Center Key Laboratory of Molecular Target&Clinical Pharmacology and the State Key Laboratory of Respiratory DiseaseSchool of Pharmaceutical Sciences&the Second Affiliated HospitalGuangzhou Medical UniversityGuangzhou 510260China CAS key laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology of ChinaBeijing 100190China

Nowadays,nanotechnology is revolutionizing the approaches to different fields from manufacture to *** nanotubes(CNTs)as promising candidates in nanomedicine have great potentials in developing novel entities for central nervous system pathologies,due to their excellent physicochemical properties and ability to interface with neurons and neuronal ***,most of the studies mainly focused on the drug delivery and bioimaging applications of CNTs,while neglect their application prospects as therapeutic drugs *** present,the relevant reviews are not available *** we summarized the latest advances on the biomedical and therapeutic applications of CNTs in vitro and in vivo for neurological diseases treatments as inherent therapeutic *** biological mechanisms of CNTs-mediated bio-medical effects and potential toxicity of CNTs were also intensely *** is expected that CNTs will exploit further neurological applications on disease therapy in the near future.

关键词： Carbon nanotubes Nervous system diseases Drug delivery Therapeutic drug Inherent medication Toxicity

Discovery of Kaempferol,a Novel ADAM10 Inhibitor,as a Potential Treatment for Staphylococcus aureus Infection

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Engineering 2023年第9期28卷 206-221页

作者： Tingting Wang Jianfeng Wang Xiangzhu Xu Fan Jiang Hongfa Lv Qinghui Qi Can Zhang Qianghua Lv Xuming Deng Department of respiratory Medicine Center for Pathogen Biology and Infectious Diseases&Key Laboratory of Organ Regeneration and Transplantation of the Ministry of EducationState Key Laboratory for Zoonotic DiseasesThe First Hospital of Jilin UniversityChangchun 130021China state key laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases&key laboratory of Zoonosis Research Ministry of EducationInstitute of ZoonosisCollege of Veterinary MedicineJilin UniversityChangchun 130062China key laboratory for Molecular Enzymology and Engineering of Ministry of Education School of Life SciencesJilin UniversityChangchun 130012China key laboratory of Livestock and Poultry Multi-omics of MARA&Shandong key laboratory of Animal Disease Control and Breeding Institute of Animal Science and Veterinary MedicineShandong Academy of Agricultural SciencesJinan 250100China

Host-directed therapy(HDT)is an emerging novel approach for treating multidrug-resistant Staphylococcus aureus(***)*** as the indispensable specific cellular receptor for a-toxin(Hla),a-disintegrin and metalloproteinase 10(ADAM10)is exploited to accelerate *** infection through diverse *** extraordinary contribution of ADAM10 to *** pathogenesis renders it an attractive HDT target for combating *** *** study is the first to demonstrate the indispensable role of ADAM10 in ***-induced necroptosis,and it enhances our knowledge of the role of ADAM10 in *** *** a fluorogenic substrate assay,we further identified kaempferol as a potent ADAM10 inhibitor that effectively protected mice from *** infection by suppressing Hla-mediated barrier disruption and ***,our work presents a novel hostdirected therapeutic strategy for using the promising candidate kaempferol to treat *** infection and other diseases relevant to the disordered upregulation of ADAM10.

关键词： Host-directed therapy Kaempferol ADAM10 inhibitor Staphylococcus aureus infection Barrier disruption Necroptosis

Longitudinal virological changes and underlying pathogenesis in hospitalized COVID-19 patients in Guangzhou,China

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Science China(Life Sciences) 2021年第12期64卷 2129-2143页

作者： Zhengtu Li Yinhu Li Ruilin Sun Shaoqiang Li Lingdan Chen Yangqing Zhan Mingzhou Xie Jiasheng Yang Yanqun Wang Airu Zhu Guoping Gu Le Yu Shuaicheng Li Tingting Liu Zhaoming Chen Wenhua Jian Qian Jiang Xiaofen Su Weili Gu Liyan Chen Jing Cheng Jincun Zhao Wenju Lu Jinping Zheng Shiyue Li Nanshan Zhong Feng Ye state key laboratory of respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China Beijing YuanShengKangTai(ProtoDNA)Genetech Co. Ltd.Beijing 100190China Department of Pulmonary and Critical Care Medicine Guangdong Second Provincial General HospitalGuangzhou 510317China Department of Computer Science City University of Hong KongHong Kong 999077China

Prolonged viral RNA shedding and recurrence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)in coronavirus disease 2019(COVID-19)patients have been ***,the clinical outcome and pathogenesis remain *** this study,we recruited 43 laboratory-confirmed COVID-19 *** found that prolonged viral RNA shedding or recurrence mainly occurred in severe/critical patients(P<0.05).The average viral shedding time in severe/critical patients was more than 50 days,and up to 100 days in some patients,after symptom ***,chest computed tomography gradually improved and complete absorption occurred when SARS-CoV-2 RT-PCR was still positive,but specific antibodies ***,the viral shedding time significantly decreased when the A1,430G or C12,473T mutation occurred(P<0.01 and FDR<0.01)and increased when G227A occurred(P<0.05 and FDR<0.05).High IL1R1,IL1R2,and TNFRSF21 expression in the host positively correlated with viral shedding time(P<0.05 and false discovery rate<0.05).Prolonged viral RNA shedding often occurs but may not increase disease *** viral RNA shedding is associated with viral mutations and host factors.

关键词： SRAS-CoV-2 longitudinal virological changes viral genome host gene expression

Natural ingredients from Chinese materia medica for pulmonary hypertension

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Chinese Journal of Natural Medicines 2021年第11期19卷 801-814页

作者： ZHANG Jia-Rui OUYANG Xuan HOU Chi YANG Qi-Feng Wu Yingjun LU Wen-Ju LIU Chun-Li YANG Kai ZHONG Nan-Shan WANG Jian CHEN Yu-Qin state key laboratory of respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangdong Key Laboratory of Vascular DiseaseGuangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510000China Division of Pulmonary and Critical Care Medicine the People’s Hospital of Inner MongoliaHuhhot 010000China Department of Neurology Guangzhou Women and Children’s Medical CenterGuangzhou 510000China Section of Physiology Division of PulmonaryCritical Care and Sleep MedicineUniversity of CaliforniaSan Diego 92173USA The Second Affiliated Hospital of Guangzhou medical university 250 Changgangdong RdGuangzhou 51026China

Pulmonary hypertension(PH)is a severe pathophysiological condition characterized by pulmonary artery remodeling and continuous increases in pulmonary artery pressure,which may eventually develop to right heart failure and *** newly discovered and incredible treatment strategies in recent years have improved the prognosis of PH,limited types of effective and economical drugs for PH still makes it as a life-threatening *** drugs from Chinese materia medica(CMM)have been traditionally applied in the treatment of lung *** evidence suggests active pharmaceutical ingredients(APIs)derived from those medicines brings promising future for the prevention and treatment of *** this review,we summarized the pharmacological effects of APIs derived from CMM which are potent in treating PH,so as to provide new thoughts for initial drug discovery and identification of potential therapeutic strategies in alternative medicine for PH.

关键词： Pulmonary hypertension Active pharmaceutical ingredients Chinese materia medica

Enantioselective[2+2]cycloaddition of 1,2-dihydroquinolines with 3-olefinic oxindoles via Brønsted acid catalysis

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Organic Chemistry Frontiers 2022年第6期9卷 1621-1627页

作者： Biao Wang Xiao Yan Han Zhong Qin Ouyang Xu Tian key laboratory of Molecular Target&Clinical Pharmacology and the state key laboratory of respiratory Disease School of Pharmaceutical Sciences&the Fifth Affiliated HospitalGuangzhou Medical UniversityXinzaoPanyu DistrictGuangzhou511436China College of Pharmacy Third Military Medical UniversityChongqing400038China

Mutually complementary regiodivergent Brønsted acid-catalyzed atom-economical[2+2]cycloadditionand ene reactions of 1,2-dihydroquinolines with 3-olefinic oxindoles are *** the presence of achiral phosphoramide catalyst,the[2+2]cycloaddition affords products with four contiguous stereocenters in good to excellent yields(up to 95%)and with high stereoselectivities(up to>99%ee,>20:1 dr).Conversely,with a stronger Brønsted acid,the trifluoromethanesulfonic acid catalyst leads to ene reactionproducts in high yields(up to 77%).Furthermore,the mechanisms of the reactions are discussed based oncontrol experiments and DFT calculations.

关键词： catalyst cycloaddition indole

Effect of early enteral nutrition on postoperative nutritional status and immune function in elderly patients with esophageal cancer or cardiac cancer

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Chinese Journal of Cancer Research 2013年第3期25卷 299-305页

作者： Guiping Yu Guoqiang Chen Bin Huang Wenlong Shao Guangqiao Zeng Department of Cardiothoracic Surgery The Affiliated Jiangyin Hospital Southeast University Medical College Department of Cardiothoracic Surgery The First Affiliated Hospital Guangzhou Medical University Guangzhou Institute of respiratory Disease (GIRD) and China State Key Laboratory of Respiratory Disease The First Affiliated Hospital Guangzhou Medical University

To explore the effect of early enteral nutrition （EN） on postoperative nutritional status, intestinal permeability, and immune 6anction in elderly patients with esophageal cancer or cardiac cancer. Methods： A total of 96 patients with esophageal cancer or cardiac cancer who underwent surgical treatment in our hospital from June 2007 to December 2010 were enrolled in this study. They were divided into EN group （n=50） and parenteral nutrition （PN） group （n=46） based on the nutrition support modes. The body weight, time to first flatus/defecation, average hospital stay, complications and mortality after the surgery as well as the liver function indicators were recorded and analyzed. Peripheral blood samples were collected on the days 1, 4 and 7 after surgery. The plasma diamine oxidase （DAO） activity and D-lactate level were determined to assess the intestinal permeability. The plasma endotoxin levels were determined using dynamic turbidimetric assay to assess the protective effect of EN on intestinal mucosal barrier. The postoperative blood levels of inflammatory cytokines and immunoglobulins were determined using enzyme- linked immunosorbent assay （ELISA）. Results： After the surgery, the time to first flatus/defecation, average hospital stay, and complications were significantly less in the EN group than those in the PN group （P〈0.05）, whereas the EN group had significantly higher albumin levels than the PN group （P〈0.05）. On the 7th postoperative day, the DAO activity, D-lactate level and endotoxin contents were significantly lower in the EN group than those in the PN group （all P〈0.05）. In addition, the EN group had significantly higher IgA, IgG, IgM, and CD4 levels than the PN group （P〈0.05） but significantly lower IL-2, IL-6, and TNF-a levels （P〈0.05）. Conclusions： In elderly patients with esophageal cancer or cardiac cancer, early EN after surgery can effectively improve the nutritional status, protect intestinal mucosal barrier （by reducing plasma endoxins）, an

关键词： Enteral nutrition nutritional status intestinal permeability endotoxin immune function