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Signal Transduction and Targeted Therapy 2022年第10期7卷 3625-3627页

作者： junxian ou Jianguo Wu Qiwei Zhang Guangdong Provincial Key Laboratory of Virology Institute of Medical MicrobiologyJinan University510632 GuangzhouChina

The recent studies published in Science and Cell Research investigated the structures and biochemical mechanism of the SARS-CoV-2 Omicron BA.1 and BA.2 spike trimer with ACE2 as well as an effective antibody JMB2002 against BA.1 and BA.2 spike,which provide new insights for the global development of broadspectrum anti-SARS-CoV-2 antibodies and vaccines.

关键词： ACE2 insight continuously

COVID-19: Antiviral Agents, Antibody Development and Traditional Chinese Medicine

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Virologica Sinica 2020年第6期35卷 685-698页

作者： Wenyi Guan Wendong Lan Jing Zhang Shan Zhao junxian ou Xiaowei Wu Yuqian Yan Jianguo Wu Qiwei Zhang Guangdong Provincial Key Laboratory of Tropical Disease Research School of Public HealthSouthern Medical UniversityGuangzhou 510515China Guangdong Provincial Key Laboratory of Virology Institute of Medical MicrobiologyJinan UniversityGuangzhou 510632GuangdongChina

The World Health Organization(WHO) has declared coronavirus disease 2019(COVID-19) is the first pandemic caused by coronavirus named severe acute respiratory syndrome coronavirus 2(SARS-CoV-2). Currently, there is no effective anti-SARS-CoV-2 drug approved worldwide for treatment of patients with COVID-19. Therapeutic options in response to the COVID-19 outbreak are urgently needed. To facilitate the better and faster development of therapeutic COVID-19 drugs, we present an overview of the global promising therapeutic drugs, including repurposing existing antiviral agents,network-based pharmacology research, antibody development and traditional Chinese medicine. Among all these drugs,we focus on the most promising drugs(such as favipiravir, tocilizumab, SARS-CoV-2 convalescent plasma, hydroxychloroquine, Lianhua Qingwen, interferon beta-1 a, remdesivir, etc.) that have or will enter the final stage of human testing—phase Ⅲ–Ⅳ clinical trials.

关键词： Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) Coronavirus disease 2019(COVID-19) Updates Drug repositioning Network-based pharmacology Antibody Traditional Chinese medicine

Construction and Characterization of a Novel Recombinant Attenuated and Replication-Deficient Candidate Human Adenovirus Type 3 Vaccine:"Adenovirus Vaccine Within an Adenovirus Vector"

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Virologica Sinica 2021年第3期36卷 354-364页

作者： Yuqian Yan Shuping Jing Liqiang Feng Jing Zhang Zhiwei Zeng Min Li Shan Zhao junxian ou Wendong Lan Wenyi Guan Xiaowei Wu Jianguo Wu Donald Seto Qiwei Zhang Guangdong Provincial Key Laboratory of Tropical Disease Research School of Public HealthSouthern Medical UniversityGuangzhou 510515China Microbiological Laboratory Zhuhai Center for Disease Control and PreventionZhuhai 519000China Guangzhou Institutes of Biomedicine and Health Chinese Academy of SciencesGuangzhou 510530China Guangdong Provincial Key Laboratory of Virology Institute of Medical MicrobiologyJinan UniversityGuangzhou 510632China Bioinformatics and Computational Biology Program School of Systems BiologyGeorge Mason UniversityManassasVA 20110USA

Human adenoviruses(HAd Vs)are highly contagious and result in large number of acute respiratory disease(ARD)cases with severe morbidity and *** adenovirus type 3(HAd V-3)is the most common type that causes ARD outbreaks in Asia,Europe,and the ***,there is currently no vaccine approved for its general *** hexon protein contains the main neutralizing epitopes,provoking strong and lasting *** this study,a novel recombinant and attenuated adenovirus vaccine candidate against HAd V-3 was constructed based on a commercially-available replication-defective HAd V-5 gene therapy and vaccine *** entire HAd V-3 hexon gene was integrated into the E1 region of the vector by homologous recombination using a bacterial *** resultant recombinants expressing the HAd V-3 hexon protein were rescued in AD293 cells,identified and characterized by RT-PCR,Western blots,indirect immunofluorescence,and electron *** potential vaccine candidate had a similar replicative efficacy as the wild-type HAd V-3 ***,and importantly,the vaccine strain had been rendered replication-defective and was incapable of replication in A549 cells after more than twentygeneration passages in AD293 *** represents a significant safety *** mice immunized both intranasally and intramuscularly by this vaccine candidate raised significant neutralizing antibodies against HAd ***,this recombinant,attenuated,and safe adenovirus vaccine is a promising HAd V-3 vaccine *** strategy of using a clinically approved and replication-defective HAd V-5 vector provides a novel approach to develop universal adenovirus vaccine candidates against all the other types of adenoviruses causing ARDs and perhaps other adenovirus-associated diseases.

关键词： Adenovirus vaccine Human adenovirus type 3(HAdV-3) Replication-deficient adenovirus vector Immunity in BALB/c mice Recombination

Tracking SARS-CoV-2 Omicron diverse spike gene mutations identifies multiple inter-variant recombination events

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Signal Transduction and Targeted Therapy 2022年第5期7卷 1808-1816页

作者： junxian ou Wendong Lan Xiaowei Wu Tie Zhao Biyan Duan Peipei Yang Yi Ren Lulu Quan Wei Zhao Donald Seto James Chodosh Zhen Luo Jianguo Wu Qiwei Zhang Guangdong Provincial Key Laboratory of Virology Institute of Medical MicrobiologyJinan University510632 GuangzhouChina BSL-3 Laboratory(Guangdong) Guangdong Provincial Key Laboratory of Tropical Disease ResearchSchool of Public HealthSouthern Medical University510515 GuangzhouChina Bioinformatics and Computational Biology Program School of Systems BiologyGeorge Mason UniversityManassasVA 20110USA Department of Ophthalmology Howe Laboratory Massachusetts Eye and EarHarvard Medical SchoolBostonMA 02114USA Foshan Institute of Medical Microbiology 528315 FoshanChina

The current pandemic of COVID-19 is fueled by more infectious emergent Omicron *** concerns of emergent variants include possible recombinants,as genome recombination is an important evolutionary mechanism for the emergence and re-emergence of human viral *** this study,we identified diverse recombination events between two Omicron major subvariants(BA.1 and BA.2)and other variants of concern(VOCs)and variants of interest(VOIs),suggesting that co-infection and subsequent genome recombination play important roles in the ongoing evolution of *** scanning high-quality completed Omicron spike gene sequences.

关键词： subsequent diverse recombination

Desmoglein 2(DSG2) Is A Receptor of Human Adenovirus Type 55 Causing Adult Severe Community-Acquired Pneumonia

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Virologica Sinica 2021年第6期36卷 1400-1410页

作者： Jing Zhang Kui Ma Xiangyu Wang Yinbo Jiang Shan Zhao junxian ou Wendong Lan Wenyi Guan Xiaowei Wu Heping Zheng Bin Yang Chengsong Wan Wei Zhao Jianguo Wu Qiwei Zhang Guangdong Provincial Key Laboratory of Virology Institute of Medical MicrobiologyJinan UniversityGuangzhou510632China Guangdong Provincial Key Laboratory of Tropical Disease Research School of Public HealthSouthern Medical UniversityGuangzhou510515China Guangdong Provincial Dermatology Hospital Southern Medical UniversityGuangzhou510091China

Human adenovirus type 55(HAdV-B55) is a re-emergent acute respiratory disease pathogen that causes adult communityacquired pneumonia(CAP). Previous studies have shown that the receptor of HAdV-B14, which genome is highly similar with HAdV-B55, is human Desmoglein 2(DSG2). However, whether the receptor of HAdV-B55 is DSG2 is undetermined because there are three amino acid mutations in the fiber gene between HAdV-B14 and HAdV-B55. Here, firstly we found the 3T3 cells, a mouse embryo fibroblast rodent cell line which does not express human DSG2, were able to be infected by HAdV-B55 after transfected with pcDNA3.1-DSG2, while normal 3T3 cells were still unsusceptible to HAdV-B55 infection. Next, A549 cells with h DSG2 knock-down by siRNA were hard to be infected by HAdV-B3/-B14/-B55, while the control siRNA group was still able to be infected by all these types of HAdVs. Finally, immunofluorescence confocal microscopy indicated visually that Cy3-conjugated HAdV-B55 viruses entered A549 cells by binding to DSG2 ***, DSG2 is a major receptor of HAdV-B55 causing adult CAP. our finding is important for better understanding of interactions between adenoviruses and host cells and may shed light on the development of new drugs that can interfere with these processes as well as for the development of potent prophylactic vaccines.

关键词： Human adenovirus type 55(HAdV-B55) Severe community-acquired pneumonia Adenovirus receptor Desmoglein 2(DSG2)

H6N6亚型禽流感病毒感染RAW264.7细胞炎症模型的建立

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经济动物学报 2024年第1期28卷 18-24页

作者：杨鑫王建俊徐浩李俊贤任涛欧德渊贵州大学动物科学学院铜仁市动物疫病预防控制中心

探讨H6N6亚型禽流感病毒的感染量、感染时间与被感染的RAW264.7细胞炎性因子水平变化的相关性，为建立RAW264.7细胞体外炎症模型提供参考。根据Reed-Muench法计算病毒滴度(TCID50)，以100 TCID50的H6N6亚型禽流感病毒感染RAW264.7细胞2 ... 详细信息

探讨H6N6亚型禽流感病毒的感染量、感染时间与被感染的RAW264.7细胞炎性因子水平变化的相关性，为建立RAW264.7细胞体外炎症模型提供参考。根据Reed-Muench法计算病毒滴度(TCID50)，以100 TCID50的H6N6亚型禽流感病毒感染RAW264.7细胞2 h，弃病毒液，加入含5%FBS的DMEM培养液继续培养，分别于12,24,48 h收集上清液或细胞，CCK8测定细胞活力；透射电子显微镜检测细胞超微结构；ELISA检测小鼠白介素-1β(IL-1β)、白介素-2(IL-2)、白介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的含量；qRT-PCR检测IL-1β、IL-2、IL-4、IL-6和TNF-α m RNA表达水平。结果表明：H6N6感染各时间段细胞活力显著下降(P<0.01)；细胞中线粒体肿胀，自噬体增多；IL-1β、IL-2、IL-6和TNF-α含量显著升高(P<0.01);IL-1β、IL-2、IL-4、IL-6和TNF-α mRNA表达水平显著升高(P<0.01)，感染24 h最高。成功构建了H6N6亚型禽流感病毒体外感染RAW264.7细胞模型，为进一步研究其致病机制提供参考。

关键词： H6N6亚型禽流感病毒 RAW264.7细胞炎症模型

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抗鸡传染性支气管炎病毒中药的筛选

中国畜牧兽医 2024年第3期51卷 1241-1249页

作者：李俊贤任涛杨剑郭杨文安林欧德渊贵州大学动物科学学院贵阳550025 贵州省动物疫病与兽医公共卫生重点实验室贵阳550025

【目的】对鸡传染性支气管炎病毒(Infectious bronchitis virus,IBV)进行抗病毒中药的筛选,并验证其治疗效果,为临床用药提供一定参考。【方法】采用鸡胚培养法,通过预防和治疗2个角度对24味单一中药、6种市售复方中药进行抗IBV的有效... 详细信息

【目的】对鸡传染性支气管炎病毒(Infectious bronchitis virus,IBV)进行抗病毒中药的筛选,并验证其治疗效果,为临床用药提供一定参考。【方法】采用鸡胚培养法,通过预防和治疗2个角度对24味单一中药、6种市售复方中药进行抗IBV的有效成分或方剂筛选试验,即在SPF鸡胚中先注射中药2 h后再接种病毒和先接种病毒2 h后再注射中药。使用SPSS 20.0软件对鸡胚重量进行方差分析,利用实时荧光定量PCR法辅助判定治疗效果。【结果】对鸡胚净重进行方差分析显示,桔梗组与阳性对照组差异显著(P0.05),表明预防和治疗均有效果。实时荧光定量PCR检测鸡胚尿囊液病毒滴度结果显示,桔梗、鱼腥草、宣肺败毒方、绞股蓝、蒲公英、甘草对IBV增殖均有抑制作用,其中桔梗抑制效果最佳。【结论】桔梗对IBV有显著的预防及抑制效果,结果为深入研究桔梗作用机理提供了依据。

关键词：鸡传染性支气管炎病毒(IBV) 鸡胚中药筛选

拉曼光谱与MCR算法分析酵母菌株间细胞乙醇发酵代谢差异

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中国激光 2022年第15期49卷 197-205页

作者：欧海声张鹏飞王晓春陈英刘军贤王桂文广西师范大学物理与技术学院广西桂林541004 广西科学院生物科学与技术研究中心广西南宁530007 天津大学精密仪器与光电子工程学院天津300072

应用拉曼镊子采集了3个酵母菌株在乙醇发酵不同时段的单细胞光谱,并利用多元曲线分辨-交替最小二乘(MCR-ALS)方法对光谱数据进行挖掘,以提取与特定生物分子相关的光谱曲线,了解不同酵母菌株的乙醇发酵代谢差异与适应机制。结果发现:工... 详细信息

应用拉曼镊子采集了3个酵母菌株在乙醇发酵不同时段的单细胞光谱,并利用多元曲线分辨-交替最小二乘(MCR-ALS)方法对光谱数据进行挖掘,以提取与特定生物分子相关的光谱曲线,了解不同酵母菌株的乙醇发酵代谢差异与适应机制。结果发现:工业菌株Bp1的发酵性能最好,实验室菌株INVSc1次之,而W303a菌株最差;MCR-ALS可从3个菌株中分别解析得到5个、5个和3个代表不同类型的生物大分子光谱曲线;Bp1菌株会增加麦角甾醇的含量和三酰基甘油的积累,以赋予细胞更高的乙醇耐受性;同时,不同生物大分子在Bp1细胞间的含量相对均一,而INVSc1和W303a菌株的胞间异质性比较大,显示出细胞异质性对菌株的发酵性能和发酵效率有重要的影响。拉曼光谱结合MCR-ALS,可以作为一个简单而强大的工具,用于快速分析酵母细胞在发酵过程中的代谢变化,进一步了解酵母细胞的抗逆机制。

关键词：生物光学拉曼光谱多元曲线分辨-交替最小二乘法乙醇发酵异质性单细胞分析

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新型全钢防屈曲支撑的拟静力滞回性能试验

土木工程学报 2011年第4期44卷 60-70页

作者：赵俊贤吴斌欧进萍哈尔滨工业大学黑龙江哈尔滨150090 大连理工大学辽宁大连116024

为减少传统防屈曲支撑(BRB)的十字形支撑内芯在焊接后所产生的残余弯曲变形,提出一种新型全角钢式防屈曲支撑(ABRB)。该支撑的内芯由4个等边角钢通过屈服段无焊接技术组合而成,约束构件则由两个等边角钢沿纵向焊接组合而成。对4个ABRB... 详细信息

为减少传统防屈曲支撑(BRB)的十字形支撑内芯在焊接后所产生的残余弯曲变形,提出一种新型全角钢式防屈曲支撑(ABRB)。该支撑的内芯由4个等边角钢通过屈服段无焊接技术组合而成,约束构件则由两个等边角钢沿纵向焊接组合而成。对4个ABRB试件进行拟静力滞回性能试验,重点考察支撑边界条件,支撑端部转动约束构造、内芯外伸段构造以及加力长度等因素对其滞回性能的影响。试验前首先对试件内芯的初始弯曲进行测量,结果表明,绝大多数试件内芯屈服段的相对初始弯曲均有效控制在1/1000以内。拟静力试验结果表明,当支撑端部边界条件为固接时,ABRB的延性及耗能发展最为充分;当支撑两端为铰接且支撑端部无转动约束时则较容易发生内芯外伸段的局部压弯破坏,且当加力长度增加时,局部压弯破坏则越早发生,但该破坏模式可通过在铰接ABRB两端设置转动约束构件的构造予以避免。对试件的抗震性能分析表明,构造合理的ABRB表现出较好的延性以及十分稳定的累积滞回耗能特性,因此ABRB可作为有效的耗能减震装置应用于工程结构中。最后提出进一步改进的建议以及有待深入研究的问题,为此类支撑性能的进一步完善奠定基础。

关键词：防屈曲支撑角钢滞回性能压弯破坏累积塑性变形

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蓖麻油基聚氨酯树脂的热降解行为研究

华南师范大学学报（自然科学版） 2022年第6期54卷 28-36页

作者：郭建维欧艺威马军现欧华新王悦辉广东工业大学轻工化工学院广州510006 电子科技大学中山学院中山528402 广东新辉化学有限公司中山528414

利用热重分析仪(TGA)、热重分析-傅里叶变换红外光谱仪(TG-FTIR)及热裂解气相色谱/质谱(PY-GC/MS)联用仪等对蓖麻油基聚氨酯树脂的热降解过程进行测试与表征,采用不同的非等温动力学方法计算树脂的热降解动力学参数,推断树脂的热降解机... 详细信息

利用热重分析仪(TGA)、热重分析-傅里叶变换红外光谱仪(TG-FTIR)及热裂解气相色谱/质谱(PY-GC/MS)联用仪等对蓖麻油基聚氨酯树脂的热降解过程进行测试与表征,采用不同的非等温动力学方法计算树脂的热降解动力学参数,推断树脂的热降解机理。结果表明:蓖麻油基聚氨酯树脂在285℃开始降解(质量损失5%),在450℃左右基本降解完全(质量损失95%)。其热降解过程(以升温速率为10℃/min为例)分为3个阶段:第一阶段发生285.23~345.25℃,其质量损失了60%,主要为树脂氨基甲酸酯键的断裂及部分酯基分解为CO_(2);第二阶段为345.25~389.17℃,质量损失了20%;主要为氨基甲酸酯链段降解为胺类、CO_(2)及含有CH_(3)或-CH_(2)-的小分子有机物;第三阶段为389.17~450.00℃,质量损失了20%,主要为小分子有机物进一步降解为CO_(2)和含N易挥发性气体。其降解机理可能有2种途径:第一种是主键氨基甲酸酯结构中酯基-O-左侧碳氧键断裂,形成异氰酸酯和醇,异氰酸酯部分裂解为胺类、二氧化碳等,而醇部分则脱水生成醛或者合成烯烃、烯酸类物质;第二种是氨基甲酸酯结构中-O-右侧碳氧键断裂生成氨基甲酸和醇类,氨基甲酸部分断裂生成伯胺和二氧化碳,醇部分裂解为醛和烯烃等。

关键词：蓖麻油基聚氨酯树脂热降解行为动力学参数降解机理