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Design, synthesis and HIV-RT inhibitory activity of novel thiazolidin-4-one derivatives

Hua CHEN, Zaihong GUO, Qingmei YIN, Xiaoxu DUAN, Yunjing GU, Xiaoliu LI

《化学科学与工程前沿（英文）》 2011年 第5卷 第2期   页码 231-237 doi: 10.1007/s11705-010-1022-7

摘要： A series of 2-aryl-3-(4,5,6-trimethylpyrimidin-2-yl) thiazolidin-4-ones ( – ) and their derivatives bearing a lipophilic substituent, like acetoxy group ( – ), propionyloxy group ( – ), methyl ( and ) at C-5 on thiazolidin-4-one ring were designed, synthesized and evaluated for their HIV-RT inhibitory activity. Using self-catalyzed Pummerer reaction, compounds – and – were obtained in good yield (63.1% 75.2%). Preliminary anti-HIV-RT test of these derivatives indicated that compounds – , (propionyloxy group at C-5) showed moderate HIV-RT inhibitory activity and compounds and with methyl at C-5 showed a weak HIV-RT inhibitory activity. Structure activity relationship analysis suggested that the substituted groups on C-5 would be unfavorable to anti-HIV-RT activity and that the steric effect might play a critical role in the anti-HIV RT activity.

关键词： 5-subsituted thiazolidin-4-ones     Pummerer reaction     anti-HIV-RT activity     SARs    

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QUANTITATIVE STUDY ON ANTI-PEST ACTIVITY OF NATURAL PRODUCTS BASED ON VISUALIZATION FRAMEWORK OF KNOWLEDGE

《农业科学与工程前沿（英文）》 2023年 第10卷 第2期   页码 306-332 doi: 10.15302/J-FASE-2023488

摘要：

● Using visual analysis to predict the trend of natural product pest resistance.

关键词： anti-pest activity     crop protection     insect pest     natural product     visual analysis    

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智能手机成像的晶片上基于逆转录环介导等温扩增(RT-LAMP)技术的全血中HIV-1检测 Article

Gregory L. Damhorst,Carlos Duarte-Guevara,Weili Chen,Tanmay Ghonge,Brian T. Cunningham,Rashid Bashir

《工程（英文）》 2015年 第1卷 第3期   页码 324-335 doi: 10.15302/J-ENG-2015072

摘要：

病毒载量测量对于人类免疫缺陷病毒 (HIV) 阳性患者长期临床护理来说是一个必不可少的工具。本文通过运用微流体和微型硅晶片平台，对经过最低程度处理的含有HIV的全血样本进行了逆转录环介导等温扩增 (RT-LAMP)，并利用智能手机进行了荧光检测。集成实验检测结果表明，一滴约60 nL的反应液滴中仅有的3个病毒依然可以通过RT-LAMP技术被检测到，这相当于每微升全血样品中只有670个病毒。该技术在数字化RT-LAMP方法上具有重要意义，扩展该技术能够实现对HIV阳性患者在临床护理中采集指血进行病毒载量检测。研究结果显示，病毒载量检测过程所需的各个步骤，从血滴的准备到RT-LAMP反应的成像，都可以集成为晶片实验并且可以和移动设备兼容。

关键词： 人类免疫缺陷病毒(HIV)     病毒载量     环介导等温扩增     智能手机     即时检测    

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Rapamycin enhances the anti-tumor activity of cabozantinib in cMet inhibitor-resistant hepatocellular

《医学前沿（英文）》 2022年 第16卷 第3期   页码 467-482 doi: 10.1007/s11684-021-0869-y

摘要： Cabozantinib, mainly targeting cMet and vascular endothelial growth factor receptor 2, is the second-line treatment for patients with advanced hepatocellular carcinoma (HCC). However, the lower response rate and resistance limit its enduring clinical benefit. In this study, we found that cMet-low HCC cells showed primary resistance to cMet inhibitors, and the combination of cabozantinib and mammalian target of rapamycin (mTOR) inhibitor, rapamycin, exhibited a synergistic inhibitory effect on the in vitro cell proliferation and in vivo tumor growth of these cells. Mechanically, the combination of rapamycin with cabozantinib resulted in the remarkable inhibition of AKT, extracellular signal-regulated protein kinases, mTOR, and common downstream signal molecules of receptor tyrosine kinases; decreased cyclin D1 expression; and induced cell cycle arrest. Meanwhile, rapamycin enhanced the inhibitory effects of cabozantinib on the migration and tubule formation of human umbilical vascular endothelial cells and human growth factor-induced invasion of cMet inhibitor-resistant HCC cells under hypoxia condition. These effects were further validated in xenograft models. In conclusion, our findings uncover a potential combination therapy of cabozantinib and rapamycin to combat cabozantinib-resistant HCC.

关键词： hepatocellular carcinoma     cabozantinib     primary resistance     rapamycin    

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2010—2013年新疆HIV感染孕产妇妊娠结局分析

沙吾力·艾力卡,艾比拜·买买提明,王晓军

《中国工程科学》 2015年 第17卷 第6期   页码 50-52

摘要：

旨在了解新疆HIV感染孕产妇妊娠结局 。利用2010—2013年间在预防艾滋病母婴传播管理信息网络直报系统中报告的HIV感染孕产妇个案卡资料进行分析。2 256例HIV感染孕产妇平均年龄29.1岁，以维吾尔族为主，占90.65 %，初中及以下文化程度者占72.07 %，无业和农民占82.36 %（其中无业者占47.30 %），初婚占56.12 %，再婚占2次及以上妊娠者占69.68 %，有316例HIV感染孕产妇在知道自己的感染状况后仍然选择妊娠，占总数的14.01 %；再次妊娠的HIV感染孕产妇中人工终止妊娠的比例明显高于第一次接受服务的HIV感染孕产妇新疆HIV感染孕产妇知道自身感染情况后仍有选择再次妊娠者，再次妊娠者中选择人工终止妊娠的比例明显高于第一次妊娠者，提示意外妊娠的存在，建议加强HIV感染妇女预防艾滋病母婴传播咨询服务和避孕指导，减少意外妊娠的发生，使HIV感染女性能够了解相关知识从而能够做出正确的生育或妊娠选择。

关键词： HIV感染孕产妇     非意愿性妊娠     生殖健康    

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Broadly neutralizing antibodies and vaccine design against HIV-1 infection

Qian Wang, Linqi Zhang

《医学前沿（英文）》 2020年 第14卷 第1期   页码 30-42 doi: 10.1007/s11684-019-0721-9

摘要： Remarkable progress has been achieved for prophylactic and therapeutic interventions against human immunodeficiency virus type I (HIV-1) through antiretroviral therapy. However, vaccine development has remained challenging. Recent discoveries in broadly neutralizing monoclonal antibodies (bNAbs) has led to the development of multiple novel vaccine approaches for inducing bNAbs-like antibody response. Structural and dynamic studies revealed several vulnerable sites and states of the HIV-1 envelop glycoprotein (Env) during infection. Our review aims to highlight these discoveries and rejuvenate our endeavor in HIV-1 vaccine design and development.

关键词： HIV-1     broadly neutralizing antibodies     Env conformational states     vaccine design     SOSIP    

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quantification of 3′-terminal 2′-O-methylated small RNAs by utilizing oxidative deep sequencing and stem-loop RT-qPCR

《医学前沿（英文）》 2022年 第16卷 第2期   页码 240-250 doi: 10.1007/s11684-021-0909-7

摘要： The continuing discoveries of novel classes of RNA modifications in various organisms have raised the need for improving sensitive, convenient, and reliable methods for quantifying RNA modifications. In particular, a subset of small RNAs, including microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs), are modified at their 3′-terminal nucleotides via 2′-O-methylation. However, quantifying the levels of these small RNAs is difficult because 2′-O-methylation at the RNA 3′-terminus inhibits the activity of polyadenylate polymerase and T4 RNA ligase. These two enzymes are indispensable for RNA labeling or ligation in conventional miRNA quantification assays. In this study, we profiled 3′-terminal 2′-O-methyl plant miRNAs in the livers of rice-fed mice by oxidative deep sequencing and detected increasing amounts of plant miRNAs with prolonged oxidation treatment. We further compared the efficiency of stem-loop and poly(A)-tailed RT-qPCR in quantifying plant miRNAs in animal tissues and identified stem-loop RT-qPCR as the only suitable approach. Likewise, stem-loop RT-qPCR was superior to poly(A)-tailed RT-qPCR in quantifying 3′-terminal 2′-O-methyl piRNAs in human seminal plasma. In summary, this study established a standard procedure for quantifying the levels of 3′-terminal 2′-O-methyl miRNAs in plants and piRNAs. Accurate measurement of the 3′-terminal 2′-O-methylation of small RNAs has profound implications for understanding their pathophysiologic roles in biological systems.

关键词： small RNAs     2′-O-methylation     sequencing     RT-qPCR    

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检测GI和GII族人源诺如病毒双重RT-qPCR的优化设计 Article

刘丹蕾, 张子蕾, 吴清平, 田鹏, 耿浩然, 徐婷, 王大鹏

《工程（英文）》 2020年 第6卷 第4期   页码 442-448 doi: 10.1016/j.eng.2019.08.018

摘要： 为了提高HuNoV检出效率，本研究基于2010年后GenBank公布的病毒序列，分析设计了一套HuNoV检测引物和探针，并优化了一种新的双重RT-qPCR(new duplex RT-qPCR, ND-RT-qPCR以23份HuNoV临床样本为对象，评估了ND-RT-qPCR和常用RT-qPCR(Kageyama RT-qPCR)的检测性能。结果显示：ND-RT-qPCR检出所有GI族样本（5/5），而Kageyama RT-qPCR只检出两个样本（2/5）。ND-RT-qPCR检出18个GII族样本（18/18），而Kageyama RT-qPCR漏检1个样本。另外，ND-RTqPCR的灵敏度显著高于Kageyama RT-qPCR（前者Cq值低于后者Cq值）。因此，ND-RT-qPCR有助于提高HuNoV检出率，是目前该病毒检测良好的选择。

关键词： 人源诺如病毒     RT-qPCR     优化设计     引物     探针     检测    

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Practices, challenges, and opportunities: HIV/AIDS treatment with traditional Chinese medicine in China

Jian Wang, Wen Zou

《医学前沿（英文）》 2011年 第5卷 第2期   页码 123-126 doi: 10.1007/s11684-011-0124-z

摘要： Traditional Chinese medicine (TCM) has become widely used in the treatment of acquired immune deficiency syndrome (AIDS) in China in recent years. In this article, we summarize the recent major developments in human immunodeficiency virus/AIDS (HIV/AIDS) treatment with TCM. The use of TCM is associated with preventing or alleviating HIV-related symptoms, reducing treatment side effects, and improving the quality of life. The potential beneficial effects of TCM should be confirmed through extensive and rigorous trials.

关键词： HIV/AIDS     traditional Chinese medicine    

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Irreversible phenotypic perturbation and functional impairment of B cells during HIV-1 infection

Jingjing Yan, Shuye Zhang, Jun Sun, Jianqing Xu, Xiaoyan Zhang

《医学前沿（英文）》 2019年 第13卷 第3期   页码 409-409 doi: 10.1007/s11684-018-0618-z

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HIV感染孕产妇婚育状况分析

沙吾力·艾力卡,王晓军,艾比拜·买买提明

《中国工程科学》 2014年 第16卷 第5期   页码 60-62

摘要：

本文旨在了解新疆人体免疫缺陷病毒（HIV）感染孕产妇的婚育状况，从而为在感染孕产妇中开展生殖健康教育提供依据，笔者利用2010—2012 年间在预防艾滋病母婴传播管理信息网络直报系统中报告的HIV感染孕产妇个案卡资料进行分析。由此可以看出，新疆HIV感染孕产妇中再婚比例明显高于全国其他省（自治区），终止妊娠者占一定比例，因此在女性感染者中有针对性地开展生殖健康教育活动势在必行。

关键词： HIV感染孕产妇     女性感染者     婚内传播     生殖健康    

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An 84-month observational study of the changes in CD4 T-lymphocyte cell count of 110 HIV/AIDS patients

null

《医学前沿（英文）》 2014年 第8卷 第3期   页码 362-367 doi: 10.1007/s11684-014-0363-x

摘要：

This study aimed to evaluate the therapeutic effect of traditional Chinese medicine (TCM) by observing the changes in CD4 T-lymphocyte cell count of 110 cases with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) treated continuously with TCM for 84 months. Information of 110 HIV/AIDS patients from 19 provinces and cities treated with TCM from 2004 to 2013 was collected. Changes in the indexes of CD4 counts (≤200, 201–350, 351–500 and>500 cells/mm3) at five time points (0, 12, 36, 60 and 84 months) and different treatments [TCM and TCM plus antiretroviral therapy (ART)] were compared. Repeated measures test indicated no interaction between group and time (P>0.05). Degrees of increasing and decreasing CD4 count of the two groups at four different frames were statistically significant compared with the baseline. The CD4 count between the two groups was not statistically significant. For CD4 count of≤200 cells/mm3, the mean CD4 count changes were 21 and 28 cells/mm3 per year for the TCM group and TCM plus ART group, respectively. For CD4 count of 201–350 cells/mm3, the mean CD4 count changes were 6 and 25 cells/mm3 per year for the TCM group and TCM plus ART group, respectively. For CD4 count of 351–500 cells/mm3, the mean CD4 count changes were -13 and -7 cells/mm3 per year for the TCM group and TCM plus ART group, respectively. For CD4 count of>500 cells/mm3, the mean CD4 count changes were -34 and -17 cells/mm3 per year for the TCM group and TCM plus ART group, respectively. Long-term use of TCM could maintain or slow the pace of declining CD4 counts in patients with HIV/AIDS, and may achieve lasting effectiveness.

关键词： AIDS     HIV     CD4     traditional Chinese medicine     linear models    

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Natural history of HIV infection in former plasma donors in rural China

Min ZHANG, Hong SHANG, Zhe WANG, Wei-Guo CUI, Qing-Hai HU

《医学前沿（英文）》 2010年 第4卷 第3期   页码 346-350 doi: 10.1007/s11684-010-0102-x

摘要： Patients infected through commercial blood-selling practices (former plasma donors, FPDs) in China represent a unique patient population compared to individuals infected through sexual contact or intravenous drug use. FPDs all have an approximate time of human immunodeficiency virus (HIV) infection during the mid-1990s. Few studies about the natural history of HIV infection in these patients were performed. The current study focuses on characterizing the duration of asymptomatic infection as well as the time to disease and mortality of infected FPDs in China. A retrospective cohort study was conducted based on data collected from 5484 HIV-1 infected FPDs in Shangcai county, Henan province. Kaplan-Meier analysis was applied to estimate the asymptomatic duration from the time of infection to the onset of AIDS as well as the survival period from the onset of AIDS to the time of death. The estimated median asymptomatic phase was about 9.21 years, which is similar to that reported in other developing countries in Africa. The estimated median life span after the onset of symptoms was about 9.91 months, which is notably shorter than life spans reported elsewhere. This is the first large-scale retrospective study on the natural history of HIV infection in FPDs in rural China. The findings not only provide valuable insight into an understudied population, but should also serve as an important reference for patient management and care.

关键词： human immunodeficiency virus (HIV)     former plasma donor     natural history     China    

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Molecular epidemiology of Cryptococcus neoformans species complex isolates from HIV-positive and HIV-negative

Min CHEN MM, Wei-Hua PAN MD, Wan-Qing LIAO MM, Xiao-Ran LI BS, Bi-Wei FENG BS, Zhe-Xue QUAN PhD, Shao-Xi WU MD, Xiao-Ping TANG MD, Zhi-Rong YAO MD,

《医学前沿（英文）》 2010年 第4卷 第1期   页码 117-126 doi: 10.1007/s11684-010-0011-z

摘要： This study investigated the molecular types of the species complex isolates and their clinical manifestations among human immunodeficiency virus (HIV)-positive and HIV-negative patients in southeast China in the past 15 years. The molecular types of 109 isolates from 108 patients were analyzed by the PCR fingerprinting method, sequences of internal transcribed spacers of rDNA (ITS region), and sequences of the capsule-associated gene (). In HIV-positive patients, clinical isolates were grouped into molecular types VNI (75%, 15/20), VNII (15%, 3/20), and VNIII (10%, 2/20). In HIV-negative patients, the majority of the clinical isolates were grouped into molecular types VNI (72%, 64/89), VNII (13%, 12/89), VGI (12%, 11/89), VNIII (1%, 1/89), and VGII (1%, 1/89). In reference to the mating type of the isolates, 97% (106/109) were of the α, 2% (2/109) were of the α/- and 1% (1/109) were of theα/. As for the clinical manifestations of the molecular types among the patients, the average cerebrospinal fluid (CSF) pressure of the patients infected by the was higher than that of the patients infected by the . These results suggest that both HIV-positive and HIV-negative cryptococcal patients in the southeast of China are mostly infected by the strains. No strains were found in HIV-positive patients.

关键词： Cryptococcus neoformans     Cryptococcus gattii     cryptococcosis     molecular epidemiology     molecular type     mating type    

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Dihydroartemisinin increased the abundance of by YAP1 depression that sensitizes hepatocellular carcinoma to anti-PD

《医学前沿（英文）》 2023年 第17卷 第4期   页码 729-746 doi: 10.1007/s11684-022-0978-2

摘要： The effect of anti-programmed cell death 1 (anti-PD-1) immunotherapy is limited in patients with hepatocellular carcinoma (HCC). Yes-associated protein 1 (YAP1) expression increased in liver tumor cells in early HCC, and Akkermansia muciniphila abundance decreased in the colon. The response to anti-PD-1 treatment is associated with A. muciniphila abundance in many tumors. However, the interaction between A. muciniphila abundance and YAP1 expression remains unclear in HCC. Here, anti-PD-1 treatment decreased A. muciniphila abundance in the colon, but increased YAP1 expression in the tumor cells by mice with liver tumors in situ. Mechanistically, hepatocyte-specific Yap1 knockout (Yap1LKO) maintained bile acid homeostasis in the liver, resulting in an increased abundance of A. muciniphila in the colon. Yap1 knockout enhanced anti-PD-1 efficacy. Therefore, YAP1 inhibition is a potential target for increasing A. muciniphila abundance to promote anti-PD-1 efficacy in liver tumors. Dihydroartemisinin (DHA), acting as YAP1 inhibitor, increased A. muciniphila abundance to sensitize anti-PD-1 therapy. A. muciniphila by gavage increased the number and activation of CD8+ T cells in liver tumor niches during DHA treatment or combination with anti-PD-1. Our findings suggested that the combination anti-PD-1 with DHA is an effective strategy for liver tumor treatment.

关键词： hepatocellular carcinoma     YAP1     Akkermansia muciniphila     anti-PD-1     dihydroartemisinin     bile acid    

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标题 作者 时间 类型 操作

Design, synthesis and HIV-RT inhibitory activity of novel thiazolidin-4-one derivatives

Hua CHEN, Zaihong GUO, Qingmei YIN, Xiaoxu DUAN, Yunjing GU, Xiaoliu LI

期刊论文

QUANTITATIVE STUDY ON ANTI-PEST ACTIVITY OF NATURAL PRODUCTS BASED ON VISUALIZATION FRAMEWORK OF KNOWLEDGE

期刊论文

智能手机成像的晶片上基于逆转录环介导等温扩增(RT-LAMP)技术的全血中HIV-1检测

Gregory L. Damhorst,Carlos Duarte-Guevara,Weili Chen,Tanmay Ghonge,Brian T. Cunningham,Rashid Bashir

期刊论文

Rapamycin enhances the anti-tumor activity of cabozantinib in cMet inhibitor-resistant hepatocellular

期刊论文

2010—2013年新疆HIV感染孕产妇妊娠结局分析

沙吾力·艾力卡,艾比拜·买买提明,王晓军

期刊论文

Broadly neutralizing antibodies and vaccine design against HIV-1 infection

Qian Wang, Linqi Zhang

期刊论文

quantification of 3′-terminal 2′-O-methylated small RNAs by utilizing oxidative deep sequencing and stem-loop RT-qPCR

期刊论文

检测GI和GII族人源诺如病毒双重RT-qPCR的优化设计

刘丹蕾, 张子蕾, 吴清平, 田鹏, 耿浩然, 徐婷, 王大鹏

期刊论文

Practices, challenges, and opportunities: HIV/AIDS treatment with traditional Chinese medicine in China

Jian Wang, Wen Zou

期刊论文

Irreversible phenotypic perturbation and functional impairment of B cells during HIV-1 infection

Jingjing Yan, Shuye Zhang, Jun Sun, Jianqing Xu, Xiaoyan Zhang

期刊论文

HIV感染孕产妇婚育状况分析

沙吾力·艾力卡,王晓军,艾比拜·买买提明

期刊论文

An 84-month observational study of the changes in CD4 T-lymphocyte cell count of 110 HIV/AIDS patients

null

期刊论文

Natural history of HIV infection in former plasma donors in rural China

Min ZHANG, Hong SHANG, Zhe WANG, Wei-Guo CUI, Qing-Hai HU

期刊论文

Molecular epidemiology of Cryptococcus neoformans species complex isolates from HIV-positive and HIV-negative

Min CHEN MM, Wei-Hua PAN MD, Wan-Qing LIAO MM, Xiao-Ran LI BS, Bi-Wei FENG BS, Zhe-Xue QUAN PhD, Shao-Xi WU MD, Xiao-Ping TANG MD, Zhi-Rong YAO MD,

期刊论文

Dihydroartemisinin increased the abundance of by YAP1 depression that sensitizes hepatocellular carcinoma to anti-PD

期刊论文