Human immunodeficiency virus(HIV)is the primary infectious agent of acquired immunodeficiency syndrome(AIDS),and non-nucleoside reverse transcriptase inhibitors(NNRTIs)are the cornerstone of HIV treatment.In the last ...Human immunodeficiency virus(HIV)is the primary infectious agent of acquired immunodeficiency syndrome(AIDS),and non-nucleoside reverse transcriptase inhibitors(NNRTIs)are the cornerstone of HIV treatment.In the last 20 years,our medicinal chemistry group has made great strides in developing several distinct novel NNRTIs,including 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine(HEPT),thio-dihydro-alkoxy-benzyl-oxopyrimidine(S-DABO),diaryltriazine(DATA),diarylpyrimidine(DAPY)analogues,and their hybrid derivatives.Application of integrated modern medicinal strategies,including structure-based drug design,fragment-based optimization,scaffold/fragment hopping,molecular/fragment hybridization,and bioisosterism,led to the development of several highly potent analogues for further evaluations.In this paper,we review the development of NNRTIs in the last two decades using the above optimization strategies,including their structure-activity relationships,molecular modeling,and their binding modes with HIV-1 reverse transcriptase(RT).Future directions and perspectives on the design and associated challenges are also discussed.展开更多
The mathematic theory for uncertainty model of line segment are summed up to achieve a general conception, and the line error hand model of εσ is a basic uncertainty model that can depict the line accuracy and quali...The mathematic theory for uncertainty model of line segment are summed up to achieve a general conception, and the line error hand model of εσ is a basic uncertainty model that can depict the line accuracy and quality efficiently while the model of εm and error entropy can be regarded as the supplement of it. The error band model will reflect and describe the influence of line uncertainty on polygon uncertainty. Therefore, the statistical characteristic of the line error is studied deeply by analyzing the probability that the line error falls into a certain range. Moreover, the theory accordance is achieved in the selecting the error buffer for line feature and the error indicator. The relationship of the accuracy of area for a polygon with the error loop for a polygon boundary is deduced and computed.展开更多
Four empirical models are tested for fitting the T-y-x equilibrium data of ethanol-water mixture by minimizing the Root Mean Square （RMS） between equilibrium data and theoretical points. The total pressure of the co...Four empirical models are tested for fitting the T-y-x equilibrium data of ethanol-water mixture by minimizing the Root Mean Square （RMS） between equilibrium data and theoretical points. The total pressure of the correspondent data is 101.3 kPa. All models parameters are also identified. The study suggests that NRTL model fits the equilibrium data best with RMS = 0.4 %.展开更多
In order to make decisions all companies need information. As a rule, all the informatics systems of a company contain a multitude of data and turn these data into information that has to be analyzed in order to make ...In order to make decisions all companies need information. As a rule, all the informatics systems of a company contain a multitude of data and turn these data into information that has to be analyzed in order to make decisions. It is a slow process. The solution of this drawback is given by Business Intelligence （BI） applications that can help companies increase income or diminish costs by offering the executive management appropriate information on the basis of which quick and efficient decisions can be taken.The main purpose of the paper is to prove the necessity that BI tools should be used by the modem manager. Managers are aware of that by putting into practice the BI solutions, opportunities of getting control over the business process and methods are improved and better, timely analysis functions of the performance parameters can be obtained.展开更多
目的研究红枣多糖对体外培养肝癌细胞增殖的抑制作用并初步探究其可能的作用机理。方法采用MTT法测定红枣多糖对体外培养的人肝癌细胞HepG2增殖的抑制作用;流式细胞术检测红枣多糖对人肝癌细胞HepG2周期和凋亡的影响;Real time RT-PCR...目的研究红枣多糖对体外培养肝癌细胞增殖的抑制作用并初步探究其可能的作用机理。方法采用MTT法测定红枣多糖对体外培养的人肝癌细胞HepG2增殖的抑制作用;流式细胞术检测红枣多糖对人肝癌细胞HepG2周期和凋亡的影响;Real time RT-PCR检测红枣多糖对人肝癌细胞HepG2中Bcl-2和caspase3mRNA表达的影响。结果 MTT检测发现随着药物浓度的增高OD值呈现梯度递减,红枣多糖对HepG2的IC50=13mg/mL,最高浓度40mg/mL下所得最大抑制率为68.79%;流式细胞仪检测细胞凋亡结果可见早期凋亡率随药物浓度的增加而变大;流式细胞周期分析结果可见G0-G1期细胞数逐渐增多,S期细胞数有下降趋势,并有剂量依赖性;Real time RT-PCR检测发现Bcl-2凋亡抑制基因mRNA表达随药物浓度增高而降低,而凋亡关键基因caspase-3mRNA的表达随药物浓度增高而升高。结论红枣多糖对体外培养的肝癌细胞增值具有抑制作用,将肝癌细胞HepG2阻滞于G1期,并通过下调Bc 1-2而上调caspase-3mRNA表达诱导HepG2细胞凋亡。展开更多
基金funded by grants from the National Natural Science Foundation of China(81872791 and 21372050)the Young Elite Scientists Sponsorship Program by the China Association forScience and Technology(2017QNRC061)+1 种基金National Key R&D Program of China(2017YFA0506000)the Key Research and Development Program of Ningxia(2019BFG02017 and 2018BFH02001,China)
文摘Human immunodeficiency virus(HIV)is the primary infectious agent of acquired immunodeficiency syndrome(AIDS),and non-nucleoside reverse transcriptase inhibitors(NNRTIs)are the cornerstone of HIV treatment.In the last 20 years,our medicinal chemistry group has made great strides in developing several distinct novel NNRTIs,including 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine(HEPT),thio-dihydro-alkoxy-benzyl-oxopyrimidine(S-DABO),diaryltriazine(DATA),diarylpyrimidine(DAPY)analogues,and their hybrid derivatives.Application of integrated modern medicinal strategies,including structure-based drug design,fragment-based optimization,scaffold/fragment hopping,molecular/fragment hybridization,and bioisosterism,led to the development of several highly potent analogues for further evaluations.In this paper,we review the development of NNRTIs in the last two decades using the above optimization strategies,including their structure-activity relationships,molecular modeling,and their binding modes with HIV-1 reverse transcriptase(RT).Future directions and perspectives on the design and associated challenges are also discussed.
基金Project supported by the National Natural Science Foundation of China (No.40301043) .
文摘The mathematic theory for uncertainty model of line segment are summed up to achieve a general conception, and the line error hand model of εσ is a basic uncertainty model that can depict the line accuracy and quality efficiently while the model of εm and error entropy can be regarded as the supplement of it. The error band model will reflect and describe the influence of line uncertainty on polygon uncertainty. Therefore, the statistical characteristic of the line error is studied deeply by analyzing the probability that the line error falls into a certain range. Moreover, the theory accordance is achieved in the selecting the error buffer for line feature and the error indicator. The relationship of the accuracy of area for a polygon with the error loop for a polygon boundary is deduced and computed.
文摘Four empirical models are tested for fitting the T-y-x equilibrium data of ethanol-water mixture by minimizing the Root Mean Square （RMS） between equilibrium data and theoretical points. The total pressure of the correspondent data is 101.3 kPa. All models parameters are also identified. The study suggests that NRTL model fits the equilibrium data best with RMS = 0.4 %.
文摘In order to make decisions all companies need information. As a rule, all the informatics systems of a company contain a multitude of data and turn these data into information that has to be analyzed in order to make decisions. It is a slow process. The solution of this drawback is given by Business Intelligence （BI） applications that can help companies increase income or diminish costs by offering the executive management appropriate information on the basis of which quick and efficient decisions can be taken.The main purpose of the paper is to prove the necessity that BI tools should be used by the modem manager. Managers are aware of that by putting into practice the BI solutions, opportunities of getting control over the business process and methods are improved and better, timely analysis functions of the performance parameters can be obtained.
文摘目的研究红枣多糖对体外培养肝癌细胞增殖的抑制作用并初步探究其可能的作用机理。方法采用MTT法测定红枣多糖对体外培养的人肝癌细胞HepG2增殖的抑制作用;流式细胞术检测红枣多糖对人肝癌细胞HepG2周期和凋亡的影响;Real time RT-PCR检测红枣多糖对人肝癌细胞HepG2中Bcl-2和caspase3mRNA表达的影响。结果 MTT检测发现随着药物浓度的增高OD值呈现梯度递减,红枣多糖对HepG2的IC50=13mg/mL,最高浓度40mg/mL下所得最大抑制率为68.79%;流式细胞仪检测细胞凋亡结果可见早期凋亡率随药物浓度的增加而变大;流式细胞周期分析结果可见G0-G1期细胞数逐渐增多,S期细胞数有下降趋势,并有剂量依赖性;Real time RT-PCR检测发现Bcl-2凋亡抑制基因mRNA表达随药物浓度增高而降低,而凋亡关键基因caspase-3mRNA的表达随药物浓度增高而升高。结论红枣多糖对体外培养的肝癌细胞增值具有抑制作用,将肝癌细胞HepG2阻滞于G1期,并通过下调Bc 1-2而上调caspase-3mRNA表达诱导HepG2细胞凋亡。
