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Development of Novel Therapeutics for Chronic Hepatitis B

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Virologica Sinica 2010年第4期25卷 294-300页

作者： you-hua xie Ran HONG Wei LIU Jing LIU Jian-wei ZHAI Key Laboratory of Medical Molecular Virology Shanghai Medical College Fudan University Shanghai 200032 China Institutes of Biomedical Sciences Fudan University Shanghai 200032 China Institute of Biochemistry and Cell Biology Shanghai Institutes of Biological Sciences Chinese Academy of Sciences Shanghai 200031 China

Chronic infection of hepatitis B virus (HBV) presents one of the serious public health challenges worldwide. Current treatment of chronic hepatitis B (CHB) is limited, and is composed of interferon and nucleoside/nucleotide reverse transcriptase inhibitors (NRTI). Interferon is poorly tolerated and is only responsive in a small fraction of CHB patients and NRTIs often face the problem of emergence of drug resistance during long-term treatment. The current treatment of CHB can be improved in several ways including genotyping mutations associated with drug resistance before treatment to guide the choice of NRTIs and suitable combinations among NRTIs and interferon. It is important to continue research in the identification of novel therapeutic targets in the life cycle of HBV or in the host immune system to stimulate the development of new antiviral agents and immunotherapies. Several antiviral agents targeting HBV entry, cccDNA, capsid formation, viral morphogenesis and virion secretion, as well as two therapeutic vaccines are currently being evaluated in preclinical studies or in clinical trials to assess their anti-HBV efficacy.

关键词： Hepatitis B virus (HBV) Treatment Chronic infection Antiviral

Identification of bis-benzylisoquinoline alkaloids as SARS-CoV-2 entry inhibitors from a library of natural products

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Signal Transduction and Targeted Therapy 2021年第4期6卷 1113-1115页

作者： Chang-Long He Lu-Yi huang Kai Wang Chen-Jian Gu Jie Hu Gui-Ji Zhang Wei Xu you-hua xie Ni Tang Ai-Long huang Key Laboratory of Molecular Biology for Infectious Diseases(Ministry of Education) Institute for Viral HepatitisDepartment of Infectious DiseasesThe Second Affiliated HospitalChongqing Medical UniversityChongqingChina Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS) Department of Medical Microbiology and ParasitologySchool of Basic Medical SciencesShanghai Medical CollegeFudan UniversityShanghaiChina Children's Hospital Fudan UniversityShanghaiChina

Dear Editor,Coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is a major public health *** spike(S)protein mutation D614G became dominant in SARS-CoV-2 during a global pandemic,which displayed increased infectivity.1 Entry of a virus into host cells is one of the most critical steps in the viral life *** blockade of the entry process is a promising therapeutic option for COVID-19,research attention has been focused on the discovery of viral entry *** SARS-CoV-2 entry inhibitor development is very attractive,no candidates have progressed into clinical trials yet.

关键词： acute respiratory attractive

Expression, Purification and Sublocalization of SARS-CoV Nucleocapsid Protein in Insect Cells

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Acta Biochimica et Biophysica Sinica 2004年第11期36卷 754-758页

作者： Ai-Xia REN, you-hua xie, Yu-Ying KONG, Guan-Zhen YANG, Yao-Zhou ZHANG,Yuan WANG, and Xiang-Fu WUInstitute of Biochemistry and Biotechnology, College of Life Science, Zhejiang University, Hangzhou 310029, China State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and cell Biology, Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China Institute of Biochemistry, Zhejiang University of Sciences, Hangzhou 310018, China Institute of Biochemistry and Biotechnology College of Life Science Zhejiang University Hangzhou 310029 China.

The causative agent of severe acute respiratory syndrome (SARS) is a previously unidentified coronavirus, SARS-CoV. The nucleocapsid (N) protein of SARS-CoV is a major viral protein recognized by acute and early convalescent sera from SARS patients. To facilitate the studies on the function and structure of the N protein, this report describe the expression and purification of recombinant SARS-CoV N protein using the baculovirus

关键词： severe acute respiratory syndrome (SARS) SARS coronavirus nucleocapsid protein baculovirus insect cells

Identification of an epitope of SARS-coronavirus nucleocapsid protein

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Cell Research 2003年第3期13卷 141-145页

作者： YING LIN,XU SHEN,RUI FU YANG,YI XUE LI,YONG YONG JI,you Yu HE,MU DE SHI,WEI LU,TIE LIU SHI,JIN WANG,HONG XIA WANG,hua LIANG JIANG,JIAN hua SHEN,you hua xie,YUAN WANG,GANG PEI,BEI FEN SHEN,JIA RUI WU,BING SUNInstitute of Biochemistry and Cell Biology,Institute of Materia Medico,,Bioinformation Center,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences. Shanghai 200031,ChinaInstitute of Microbiology and Epidemiology,Institute of Basic Medical Sciences,Academy of Military Medical,Sc.imce.fi,Beijing 100071,China Institute of Biochemistry and Cell Biology Chinese Academy of Sciences Shanghai 200031 China.

The nucleocapsid(N)protein of severe acute respiratory syndrome-coronavirus(SARS-CoV)is a majorvirion structural *** this study,two epitopes(N1 and N2)of the N protein of SARS-CoV werepredicted by bioinformatics *** immnnization with two peptides,the peptides-specific antibodieswere isolated from the immunized *** further experiments demonstrated that N1 peptide-inducedpolyclonal antibodies had a high affinity to bind to *** expressed Nprotein of ***,itwas confirmed that N1 peptide-specific IgG antibodies were detectable in the sera of severe acute respiratorysyndrome(SARS)*** results indicated that an epitope of the N protein has been identified andN protein specific Abs were produced by peptide immunization,which will be useful for the study of SARS-CoV.

关键词： severe acute respiratory syndrome-coronavirus necleocapsid protein epitope polyclonal antibody antiserum.

Effect of strain rate on the compressive deformation behaviors of lotus-type porous copper

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International Journal of Minerals,Metallurgy and Materials 2014年第7期21卷 687-695页

作者： Xin-hua Liu Hai-you huang Jian-xin xie Institute for advanced Materials and Technology University of Science and Technology Beijing Key Laboratory for Advanced Materials Processing(MOE) University of Science and Technology Beijing

Lotus-type porous copper was fabricated by unidirectional solidification, and compressive experiments were subsequently conducted in the strain rate range of 10-3-2400 s-1 with the compressive direction parallel to the pores. A GLEEBLE-1500 thermal-mechanical simulation system and a split Hopkinson pressure bar （SHPB） were used to investigate the effect of strain rate on the compressive deforma-tion behaviors of lotus-type porous copper. The influence mechanism of strain rate was also analyzed by the strain-controlling method and by high-speed photography. The results indicated that the stress-strain curves of lotus-typed porous copper consist of a linear elastic stage, a plateau stage, and a densification stage at various strain rates. At low strain rate （〈1.0 s^-1）, the strain rate had little influence on the stress-strain curves; but when the strain rate exceeded 1.0 s^-1, it was observed to strongly affect the plateau stage, showing obvious strain-rate-hardening characteristics. Strain rate also influenced the densification initial strain. The densification initial strain at high strain rate was less than that at low strain rate. No visible inhomogeneous deformation caused by shockwaves was observed in lotus-type porous copper during high-strain-rate deformation. However, at high strain rate, the bending deformation characteristics of the pore walls obviously differed from those at low strain rate, which was the main mechanism by which the plateau stress exhibited strain-rate sensitivity when the strain rate exceeded a certain value and exhibited less densification initial strain at high strain rate.

关键词： porous materials copper directional solidification strain rate sensitivity deformation modes stress-strain curves

Squeezing in the Thermal Jaynes-Cummings Model

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Chinese Physics Letters 1996年第6期13卷 432-435页

作者： xie Rui-hua ZOU you-tao LIU Dun-huan Department of Physics Nanjing UniversityNanjing 210008 Department of Physics Wuhan UniversityWuhan 430072 National Laboratory of Solid State Microstructures Institute for Solid State Physics Center for Advanced Studies in Science and Technology of Microstructures Nanjing UniversityNanjing 210008

We have studied the influence of thermal photons on the symmetry between the field and atomic squeezing(SFAS)exposed in the resonant vacuum-field Jaynes-Cummings model with an initially coherent *** have shown that when the number of thermal photons(Nav)is less than 0.01,the SFAS is not sensitive to the presence of thermal photons;when Nav≥0.01,the broken SFAS can be seen;when Nav≥0.1,the squeezed atom cannot radiate a squeezed field any ***,we have discussed the possibility of detection of the boken symmetry in superconducting maser cavity.

关键词： symmetry Cummings resonant

Quantification of Trace Amounts of Impurities in High Purity Cobalt by High Resolution Inductively Coupled Plasma Mass Spectrometry

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Chinese Chemical Letters 2006年第8期17卷 1077-1080页

作者： hua Lin xie Xi Du NIE you Gen TANG Department of Chemistry Hunan Institute of Technology Hengyang 421008 School of Chemistry and Chemical Engineering Central south university Changsha 410083

An analytical method using high resolution inductively coupled plasma mass spectrometry （HR-ICP-MS） for rapid simultaneous determination of Be, Mg, Al, Ti, V, Cr, Mn, Fe, Ni, Cu, Zn, Ga, Ge, As, Se, Mo, Ag, Cd, Sn, Sb, Ba, Pt, Au and Pb in high purity cobalt was described. Sample digestions were performed in closed microwave vessels using HNO3 and HCl. The matrix effects due to the presence of excess HCl and Co were evaluated. The usefulness of high mass resolution for overcoming some spectral interference was demonstrated. The optimum conditions for the determination was tested and discussed. Correction for matrix effects, Sc, Rh and Bi were used as internal standards. The detection limits is 0.003-0.57 μg/g, the recovery ratio is 92.2%-111.2%, and the RSD is less than 3.6%. The method is accurate, quick and convenient. It has been applied to the determination of trace impurities in high purity cobalt with satisfactory results.

关键词： High resolution inductively coupled plasma mass spectrometry high purity cobalt,trace impurities matrix effect spectral interference internal standards.

The spike protein of severe acute respiratory syndrome (SARS) is cleaved in virus infected Vero-E6 cells

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Cell Research 2004年第5期14卷 400-406页

作者： Xiao Dong WU 1*, Bo SHANG1*, Rui Fu YANG2*, Hao YU3*, Zhi Hai MA1*, Xu SHEN3*, Yong Yong JI1, Ying LIN , Ya Di WU1, Guo Mei LIN1, Lin TIAN1, Xiao Qing GAN1, Sheng YANG2, Wei Hong JIANG2, 1 Er Hei DAI4, Xiao Yi WANG4, hua Liang JIANG3, you hua xie1, Xue Liang ZHU1, Gang PEI1, Lin LI1, Jia Rui WU1**, Bing SUN 1** 1Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China. 2Institute of Microbiology and Epidemiology, Institute of Basic Medical Sciences, Academy of Military Medical Sciences, Beijing 100071, China. 3Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 300 Fenglin Road, Shanghai 200031, China. 3Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Taiyuan Road, Shanghai 200031, China. Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences 320 Yueyang Road Shanghai 200031 China.

Spike protein is one of the major structural proteins of severe acute respiratory syndrome-coronavirus. It is essential for the interaction of the virons with host cell receptors and subsequent fusion of the viral envelop with host cell membrane to allow infection. Some spike proteins of coronavirus, such as MHV, HCoV-OC43, AIBV and BcoV, are proteolytically cleaved into two subunits, S1 and S2. In contrast, TGV, FIPV and HCoV-229E are not. Many studies have shown that the cleavage of spike protein seriously affects its function. In order to investigate the maturation and proteolytic processing of the S protein of SARS CoV, we generated S1 and S2 subunit specific antibodies (Abs) as well as N, E and 3CL protein-specific Abs. Our results showed that the antibodies could efficiently and specifically bind to their corresponding proteins from *** expressed or lysate of SARS-CoV infected Vero-E6 cells by Western blot analysis. Furthermore, the anti-S1 and S2 Abs were proved to be capable of binding to SARS CoV under electron microscope observation. When S2 Ab was used to perform immune precipitation with lysate of SARS-CoV infected cells, a cleaved S2 fragment was detected with S2-specific mAb by Western blot analysis. The data demonstrated that the cleavage of S protein was observed in the lysate, indicating that proteolytic processing of S protein is present in host cells.

关键词： SARS-CoV spike protein nucleocapsid protein envelope protein 3CL protease polyclonal antibody.

Effects of RRA Treatments on Microstructures and Properties of a New High-strength Aluminum-Lithium Alloy-2A97

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Chinese Journal of Aeronautics 2007年第2期20卷 187-192页

作者： YUAN Zhi-shan LU Zheng xie you-hua DAI Sheng-long LIU Chang-sheng School of Materials ＆ Metallurgy Northeastern University Shenyang 110004 China Beijing Institute of Aeronautical Materials Beijing 100095 China

A new high strength 2A97 Al-Cu-Li-X alloy was subjected to triple-aging of retrogression and re-aging treatments （RRA）. Transmission electron microscopy （TEM）, differential scanning calorimetry （DSC）, and tensile tests were used to investigate the effects of RRA treatment on the microstructures and properties. DSC test reveals the reversion temperature range of the strengthening δ＇（Al3Li） phase. The results show that the microstructure consists of δ＇（Al3Li） phase, T1 （Al2CuLi） phase and θ″/θ′（Al2Cu） phase for 2A97 alloy treated by a triple-aging of a retrogression and re-aging treatment in the following order：（1） at 165℃×30 min, （2） at 220 ℃ or 240℃ × 15 min, （3） at 165℃×24 h. The plastic deformation, incorporated into the treatment after secondary high temperature aging, promotes the T1 precipitation during final re-aging. The tensile properties of the alloy treated by the retrogression and re-aging treatment reach the peak level of alloy single-aged at 165℃ in T6 temper.

关键词： 2A97 Al-Cu-Li-X alloy RRA treatments triple aging microstructure reversion