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Comparative Antiviral Efficacy of Viral Protease Inhibitors against the Novel SARS-CoV-2 In Vitro

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Virologica Sinica 2020年第6期35卷 776-784页

作者： Leike Zhang Jia Liu Ruiyuan Cao Mingyue Xu Yan wu weijuan Shang Xi wang Huanyu Zhang Xiaming Jiang Yuan Sun Hengrui Hu Yufeng Li Gang Zou Min Zhang Lei Zhao wei Li Xiaojia Guo Xiaomei Zhuang Xing-Lou Yang Zheng-Li Shi Fei Deng Zhihong Hu Gengfu Xiao Manli wang wu Zhong State Key Laboratory of Virology Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan 430071China National Engineering Research Center for the Emergency Drug Beijing Institute of Pharmacology and ToxicologyBeijing 100850China CAS Key Laboratory of Molecular Virology and Immunology Institute Pasteur of ShanghaiChinese Academy of SciencesShanghai 200031China

The recent outbreak of novel coronavirus pneumonia(COVID-19)caused by a new coronavirus has posed a great threat to public *** safe and effective antivirals is of urgent demand to cure the huge number of *** proteases are considered potential drug *** human immunodeficiency virus protease inhibitors(lopinavir/ritonavir)has been recommended in the global Solidarity Trial in March launched by World Health ***,there is currently no experimental evidence to support or against its clinical *** evaluated the antiviral efficacy of lopinavir/ritonavir along with other two viral protease inhibitors in vitro,and discussed the possible inhibitory mechanism in *** in vitro to in vivo extrapolation was carried out to assess whether lopinavir/ritonavir could be effective in *** the four tested compounds,lopinavir showed the best inhibitory effect against the novel coronavirus ***,further in vitro to in vivo extrapolation of pharmacokinetics suggested that lopinavir/ritonavir could not reach effective concentration under standard dosing regimen[marketed as Kaletraò,contained lopinavir/ritonavir(200 mg/50 mg)tablets,recommended dosage is 400 mg/10 mg(2 tablets)twice daily].This research concluded that lopinavir/ritonavir should be stopped for clinical use due to the huge gap between in vitro IC50 and free plasma ***,the structure–activity relationship analysis of the four inhibitors provided further information for de novel design of future viral protease inhibitors of SARS-CoV-2.

关键词： Respiratory pharmacology COVID-19 SARS-CoV-2 Protease inhibitor

The Application of the Bursa Model to the Integration of GPS Time Series

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Earthquake Research in China 2014年第1期28卷 46-53页

作者： wang Ziyan Lin Shu wu Yanqiang Zhan wei Ding Xiaoguang Earthquake Administration of Fujian Province Institute of Earthquake Science CEA First Crustal Monitoring and Application Center CEA Earthquake Administration of Shaanxi Province

In this paper the method of combining the Bursa model to integrate several regional time series to derive a unified global time series is introduced in detail. Then,an example taken from CMONOC( Crustal Movement Observation Network of China) is used to test if the combination method is feasible. The precision of the integrated time series with the combination method is below 2mm( North),3mm( East),that is same as the results from the direct integration of the time series and the precision of the baseline is below 6mm,which proves that the combination method can be used to integrate several regional time series to derive a unified global time series.

关键词： GPS time series Integration Bursa model

Influence of CD133^+ expression on patients' survival and resistance of CD133^+ cells to anti-tumor reagents in gastric cancer

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Asian Pacific Journal of Tropical Biomedicine 2015年第12期5卷 996-1004页

作者： De-Hu Chen Rui-Qi Lu Xiao-Chun Ni Ju-Gang wu Shou-Lian wang Bo-Jian Jiang Ji-wei Yu Department of General Surgery Third People's Hospital Shanghai Jiao Tong University School of Medicine

Objective:To investigate the influence of CD133+expression on patients'survival and resistance of CD133+cells to anti-tumor agents in gastric cancer(GC).Methods:Influence of CD133 expression on prognosis was analyzed employing samples from patients with *** cell lines were utilized to separate CD133+and CD133-subpopulations by immunomagnetic separation and to analyze the biological features of two subpopulations in vitro and in vivo,especially in resistant to anti-tumor reagents and its apoptotic ***:The lower CD133+group showed a significantly better survival compared with the higher CD133+*** highest content of CD133+subpopulations for KATO-III cells had stronger proliferative ability than CD133-subpopulations.A single CD133+cell was capable of generating new cell colony and the tumorigenicity rate in nude mice was100%for CD133+clonal spheres or for CD133+cells,but 0%for ***,the higher expression levels of Oct-4,Sox-2,Musashi-1 and ABCG2 in CD133+clonal spheres were identified compared with CD133+cells or *** the treatment of anti-tumor reagents,CD133+cells had lower suppression rates compared with CD133-cells while lower level of Bcl-2 and higher level of Bax were found in CD133+cells compared with ***:The patients with lower CD133+expression had a better *** CD133+cells in clonal sphere shared the ability to be self-renewable,proliferative,tumorigenic and resistant to anti-tumor agents as probably regulated by Bcl-2 and Bax.

关键词： Stomach Cancer CD133 Tumor initiating cells

Strategy of Systems Biology for Visualizing the “Black Box” of Traditional Chinese Medicine

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World Journal of Traditional Chinese Medicine 2020年第3期6卷 260-270页

作者： Yu Gu Gao-Song wu Hou-Kai Li wei-Dong Zhang Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese MedicineShanghaiChina Department of Phytochemistry College of PharmacySecond Military Medical UniversityShanghaiChina

Traditional Chinese medicine(TCM)has been practiced for thousands of years in *** formula,usually composed of several or even dozens of herbal medicines,is the main form of TCM practicing,which is extremely complex due to multiple components and therapeutic targets,especially the characteristics of formula ***,it is an enormous challenge for the modernization of *** biology is a strategy for investigating the complex interactions between genes,mRNA,proteins,and metabolites by using integrated omics *** recent years,systems biology has been increasingly adopted in TCM *** review comprehensively summarized status of syndrome and application of TCM formulae in clinical and preclinical studies and discussed the advances of systems biology in TCM ***,a"Disease-Syndrome-Formulae-Effect"strategy was proposed for TCM *** of systems biology and"Disease-Syndrome-Formulae-Effect"strategy provided a novel approach to understand the complex interactions among biological systems,drugs,and complex diseases from a network perspective,thus facilitating the modernization of *** objective of this manuscript is to provide comprehensive and up-to-date review on the application of systems biology in TCM research,as well as the perspective of TCM modernization with systems biology.

关键词： Formula omics systems biology traditional Chinese medicine

Gasser-Leutwyler Coefficients of Chiral Lagrangian for Pseudoscalar Goldstone Bosons

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Communications in Theoretical Physics 2006年第1X期46卷 101-108页

作者： ZHOU Li-Juan wu Qing PAN Ji-Huan MENG Cheng-Ju MA wei-Xing LI Xi-Guo Collaboration Group of Hadron Physics and Non-perturbative QCD Study Guangxi University of Technology Liuzhou 545006 China Department of Physics Qingdao University Qingdao 266071 China Department of Physics Hechi College Yizhou 546300 China Institute of High Energy Physics the Chinese Academy of Sciences Beijing 100049 China Institute of Modern Physics the Chinese Academy of Sciences Lanzhou 730000 China

Based on the Dyson-Schwinger equations in raAnbow approximation for quark propagator with an effective gluon propagator, and on the parametrized fully dressed quark propagator proposed by us, the unknown GasserLeutwyler coeiticients of the chiral Lagrangian for pseudoscalar Goldstone bosons, Li, are predicted respectively. The predicted values of Li in the two different ways are not only in reasonable agreement each other but also in agreement with empirical values used widely in literature and the values predicted by many other theoretical models with QCD characteristics. The compatible results of Gasser-Leutwyler coefficients predicted by our parameterized quark propagator, in turn, clearly verify its extensive validity.

关键词： chiral perturbation theory Gasser-Leutwyler coefficient quark propagator Dyson-Schwinger equations

Evaluation of the Mechanisms Underlying Amino Acid and Microbiota Interactions in Intestinal Infections Using Germ-Free Animals

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Infectious Microbes & Diseases 2021年第2期3卷 79-86页

作者： Yapeng Yang Peng Bin Shiyu Tao Guoqiang Zhu Zhifeng wu wei Cheng Wenkai Ren Hong wei State Key Laboratory of Agricultural Microbiology College of Animal Sciences and TechnologyHuazhong Agricultural UniversityWuhanHubeiChina Jiangsu Co-Innovation Center for Important Animal Infectious Diseases and Zoonoses Joint International Research Laboratory of Agriculture and AgriProduct Safety of Ministry of Education of ChinaCollege of Veterinary MedicineYangzhou UniversityYangzhouJiangsuChina State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources Guangdong Laboratory of Lingnan Modern AgricultureNational Engineering Research Center for Breeding Swine IndustryGuangdong Provincial Key Laboratory of Animal Nutrition ControlCollege of Animal ScienceSouth China Agricultural UniversityGuangzhouGuangdongChina

Intestinal infectious diseases refer to the inflammatory changes in the intestinal tract caused by pathogens(including bacteria,viruses,fungi,protozoa,or parasites)or their toxic products.A large number of microorganisms colonize the intestinal tract of healthy people,which together with the intestinal epithelium constitute the biological barrier of the intestinal tract to resist infectious *** an“invisible organ,”the intestinal flora is closely related to human nutrition metabolism and intestinal infections.A variety of intestinal flora participates in the nutritional metabolism of amino acids,and the small molecular substances produced by the amino acid metabolism through the intestinal flora can enhance intestinal immunity and resist bacterial *** turn,amino acids can also regulate the composition of the intestinal flora,maintain the steady-state of the intestinal flora,protect the intestinal barrier,and inhibit colonization by pathogenic *** a model animal with a clear microbial background,germ-free(GF)animals can clarify the mechanisms of interactions between intestinal microbes and amino acid metabolism in intestinal infections by combining genetic engineering technology and multi-omics *** article reviews related researches on the involvement of intestinal microbes in host amino acid metabolism and resistance to intestinal infections and discusses the advantages of GF animal models for studying the underlying *** GF animal model is helpful to further study the intervention effects of amino acid metabolism of targeted intestinal flora on intestinal infections.

关键词： germ-free animal intestinal barrier intestinal flora intestinal immunity intestinal infection metabolism of amino acids

Preparation of （2E）-3-（4＇-Halophenyl）prop-2-enoyl Sulfachlorpyridazine Sodium Salts and Their Interaction with Bovine Serum Albumin by Fluorescence Spectroscopy

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Chemical Research in Chinese Universities 2013年第5期29卷 854-860页

作者： DU Chuan-rong LUO Xuan wei Jin-rui HE Ting-ting ZHENG Xiao-yu LIN Cui-wu School of Chemistry and Chemical Engineering Guangxi University Nanning 530004 P. R. China

Three （2E）-3-（4＇-halophenyl）prop-2-enoyl sulfachlorpyridazine sodium salts（XPSCA） were synthesized. Their chemical structures were confirmed by IH NMR and 13C NMR, electrospray ionization mass spectrometry （ESI-MS）, and infrared（IR） spectroscopy. The interactions between XPSCA and bovine serum albumin（BSA） were investigated under imitated physiological condition by fluorescence quenching technique and UV-Vis absorption spectroscopy according to the Stern-Volmer equation. The results from the emission quenching at different tempera- tures indicate that the quenching mechanism of serum albumin by XPSCA was static quenching mechanism at low XPSCA concentrations or a combined quenching（static and dynamic） mechanism at higher XPSCA concentrations. At different temperatures, the binding constant and the binding sites of XPSCA with BSA were investigated, and the distances were evaluated according to F6rster non-radiative resonance energy transfer theory. The thermodynamic parameters were calculated according to van＇t Hoff equation, which implies that both van der Waals interaction and hydrogen bond played major roles in stabilizing the XPSCA-BSA complexes, whereas hydrophobic interactions were secondary. Moreover, the conformational changes in BSA were analyzed by synchronous fluorescence spectra.

关键词： Sulfachlorpyridazine sodium Bovine serum albumin Halo-cinnamic acid Fluorescence spectroscopy

Genome Analysis of the Bombyx mori Infectious Flacherie Virus Isolated in China

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Agricultural Sciences in China 2010年第2期9卷 299-305页

作者： LI Ming-qian CHEN Xiao-xue wu Xiao-xia MAN Na-na JIN wei LU Xing-meng Laboratory of Invertebrate Pathology College of Animal Sciences Zhejiang University Hangzhou 310029 P.R.China

We reported here the complete genome of the Bombyx mori infectious flacherie virus （BmlFV）, BmlFV-CHN01, isolated in China and compared it with the Japanese strain IFV （BmIFV-JAN） sequence. BmIFV-JAN and BmIFV-CHN01 were 99% identical in nucleotide and amino acid sequences. The amino acid sequences of the three structural proteins （VP1, VP3 and VP4） and L protein were 100% identical between the two strains. Phylogenetic analyses based on conserved domains in RNA-dependent RNA polymerases （RdRps） by the neighbor-joining method showed that these two strains were from the same virus. The gain of the whole genome of the BmIFV isolated in China and its weak mutation character established a great foundation to the study of functional genome and the molecular epidemiology of BmIFV.

关键词： Bombyx mori infectious flacherie virus complete genome phylogenetic analysis

Penicillium and patulin distribution in pears contaminated with Penicillium expansum. Determination of patulin in pears by UHPLC-MS/MS

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Journal of Integrative Agriculture 2017年第7期16卷 1645-1651页

作者： wei Dong-mei XU Jun DONG Feng-shou LIU Xin-gang wu Xiao-hu ZHENG Yong-quan Risk Assessment Laboratory for Biological Hazards of Agricultural Product Quality and Safety Ministry of Agriculture/Institute of Plant Protection Chinese Academy of Agricultural Sciences College of Plant Protection Shenyang Agricultural University

The danger of mycotoxin contamination entering the food supply through post-harvest infection is of perennial concern to food safety experts. To explore the distribution of Penicillium expansum and diffusion of its mycotoxin, patulin, in blue mold-damaged pears, Pyrus bretschneideri Rehd. cv. Yali obtained from markets and orchards in China were artificially inoculated with P. expansum and assayed for patulin accumulation and degree of fungal colonization. The inoculated pears were incubated until the lesions were 5, 10, 20, or 30 mm in diameter. We sampled tissue at a range of distances from the lesion, measured the spread of Penicillium by plate colony-counting methods, and used UHPLC-MS/MS to detect and quantify the patulin concentration. More P. expansum colony-forming units were isolated from pears with a higher degree of decay. Farther from the lesion, the fewer P. expansum colonies were observed, and the lower the patulin content detected. We found a significant difference in the patulin content between samples due to lesion size, and also in tissue sampled 10 mm away from the lesion. In consideration of this finding, to ensure food safety, we recommend that when a blue mold rot lesion on pear is 5, 10, or 20 mm in diameter, 20, 30, and 40 mm beyond the lesion should be removed, respectively. If a lesion surpasses 30 mm in diameter, the whole pear should be thrown away.

关键词： pear Penicillium expansum patulin food safety UHPLC-MS/MS