Apoptosis has been considered as the only form of regulated cell death for a long time. However, a novel form of programmed cell death called necroptosis was recently reported. The process of necroptosis is regulated ...Apoptosis has been considered as the only form of regulated cell death for a long time. However, a novel form of programmed cell death called necroptosis was recently reported. The process of necroptosis is regulated and plays a critical role in the occurrence and development of multiple human diseases. Thus,the study on the molecular mechanism of necroptosis and its effective inhibitors has been an attractive field for researchers. Herein, we introduce the molecular mechanism of necroptosis and focus on the literature about necroptosis drug screening in recent years. In addition, the identification of the critical drug targets of the necroptosis is also discussed.展开更多
Detecting target echo in the existence of self-screen jamming is a challenging work for radar system, especially when digital radio frequency memory(DRFM) technique is employed that mixes the jamming and target echo b...Detecting target echo in the existence of self-screen jamming is a challenging work for radar system, especially when digital radio frequency memory(DRFM) technique is employed that mixes the jamming and target echo both in spatial and time-frequency domain. The conventional way to solve this problem would suffer from performance degradation when physical target(PT) and false target(FT) are superposed in time. In this paper, we propose a new spatial filter according to the different correlation characteristic between PT and FT. The filter takes the ratio of expected signal power to expected jamming and noise power as the objective function under the constant filter modulus constraint. The optimal filter coefficients are derived with a generalized rayleigh quotient approach. Moreover, we analytically compute the target detection probability and demonstrate the applicability of the proposed method to the correlation coefficient. Monte Carlo simulations are provided to corroborate the proposed studies. Furthermore, the proposed method has simple architecture and low computation complexity, making it easily applied in modern radar system.展开更多
HIV/AIDS is one of the most serious public health challenges globally. Despite the great efforts that are being devoted to prevent,treat and to better understand the disease,it is one of the main causes of morbidity a...HIV/AIDS is one of the most serious public health challenges globally. Despite the great efforts that are being devoted to prevent,treat and to better understand the disease,it is one of the main causes of morbidity and mortality worldwide. Currently,there are 30 drugs or combinations of drugs approved by FDA. Because of the side-effects,price and drug resistance,it is essential to discover new targets,to develop new technology and to find new anti-HIV drugs. This review summarizes the major targets and assays currently used in anti-HIV drug screening.展开更多
Advanced analytical methodology based on comprehensive two-dimensional gas chromatography-time of flight mass spectrometry(GC×GC-TOFMS) is proposed for investigation of organic chlorides in different oilfield che...Advanced analytical methodology based on comprehensive two-dimensional gas chromatography-time of flight mass spectrometry(GC×GC-TOFMS) is proposed for investigation of organic chlorides in different oilfield chemicals.The target screening was initially carried out on 8 suspected organic chlorides by evaluating the capability of the enhanced separation and reliable identification at a trace concentration. GC×GC-TOFMS allowed for the fast and automated analysis of organic chlorides at a level of 200 μg/L. This method was subsequently applied for non-target screening of organic chlorides in different oilfield chemicals at various locations across China. 22 organic chlorides were identified and verified by comparison with pure standards in the mixed sample. Finally, this method was used to determine the content of the organic chlorides in individual samples. The result showed that the organic chloride levels in 19 of the 39 tested oilfield chemicals were above the threshold limit of 1.0 mg/L.展开更多
基于多靶点虚拟筛选、网络药理学分析和体外实验,探讨强肝胶囊(QGC)治疗非酒精性脂肪性肝病(NAFLD)的潜在作用机制。利用基于PPARα/γ、FXR及sEH的多靶点虚拟筛选选出QGC中具有治疗NAFLD的活性成分,运用网络药理学预测活性成分靶点、...基于多靶点虚拟筛选、网络药理学分析和体外实验,探讨强肝胶囊(QGC)治疗非酒精性脂肪性肝病(NAFLD)的潜在作用机制。利用基于PPARα/γ、FXR及sEH的多靶点虚拟筛选选出QGC中具有治疗NAFLD的活性成分,运用网络药理学预测活性成分靶点、疾病相关靶点,筛选调控疾病的关键靶点,通过Discovery Studio 2020软件和Gromacs软件对关键活性成分和关键靶点进行分子对接和分子动力学模拟分析。最后,通过实验验证QGC中的关键活性成分对肝细胞脂肪变性的改善作用。多靶点虚拟筛选得到235个QGC活性成分,网络药理学分析得到320个成分-疾病共同靶点。分子对接结果表明,芹菜素、异鼠李素、迷迭香酸、大黄素甲醚、木犀草素与关键靶点PTPN1、PPARα、PPARγ、AR具有良好的结合能力。分子动力学模拟进一步验证了迷迭香酸、大黄素甲醚等化合物与关键靶点具有良好的结合稳定性。体外实验结果显示,5个关键活性成分均能改善HepG2细胞的脂肪变性,其中异鼠李素、迷迭香酸、大黄素甲醚改善细胞脂肪变性模型的效果最佳。本研究通过多层面探讨,为QGC在NAFLD治疗中的开发和应用提供理论依据。展开更多
目的:研究抗肿瘤靶点人MutT同源体1蛋白(Human MutT Homolog-1,MTH1)抑制剂的构效关系,构建药效团筛选模型筛选潜在的MTH1抑制剂。方法:采用计算机辅助药物设计方法,通过Discovery Studio 3.0软件包中分子共同特征药效团HipHop算法,使...目的:研究抗肿瘤靶点人MutT同源体1蛋白(Human MutT Homolog-1,MTH1)抑制剂的构效关系,构建药效团筛选模型筛选潜在的MTH1抑制剂。方法:采用计算机辅助药物设计方法,通过Discovery Studio 3.0软件包中分子共同特征药效团HipHop算法,使用14个已知MTH1抑制剂分子作为训练集构建药效团模型,并通过Decoy Set验证准确性。结果:获得富集率为13.1的HipHop药效团模型,通过分子对接验证虚拟筛选出的75个候选化合物,得到先导化合物GK01945和HTS07767,能与受体形成良好的相互作用。结论:构建的药效团模型可以作为筛选模型,筛选出的MTH1潜在抑制剂,为抗肿瘤药物MTH1抑制剂开发提供了新思路。展开更多
基金supported by the National Natural Science Foundation of China (Grant No. 81503039)
文摘Apoptosis has been considered as the only form of regulated cell death for a long time. However, a novel form of programmed cell death called necroptosis was recently reported. The process of necroptosis is regulated and plays a critical role in the occurrence and development of multiple human diseases. Thus,the study on the molecular mechanism of necroptosis and its effective inhibitors has been an attractive field for researchers. Herein, we introduce the molecular mechanism of necroptosis and focus on the literature about necroptosis drug screening in recent years. In addition, the identification of the critical drug targets of the necroptosis is also discussed.
文摘Detecting target echo in the existence of self-screen jamming is a challenging work for radar system, especially when digital radio frequency memory(DRFM) technique is employed that mixes the jamming and target echo both in spatial and time-frequency domain. The conventional way to solve this problem would suffer from performance degradation when physical target(PT) and false target(FT) are superposed in time. In this paper, we propose a new spatial filter according to the different correlation characteristic between PT and FT. The filter takes the ratio of expected signal power to expected jamming and noise power as the objective function under the constant filter modulus constraint. The optimal filter coefficients are derived with a generalized rayleigh quotient approach. Moreover, we analytically compute the target detection probability and demonstrate the applicability of the proposed method to the correlation coefficient. Monte Carlo simulations are provided to corroborate the proposed studies. Furthermore, the proposed method has simple architecture and low computation complexity, making it easily applied in modern radar system.
文摘HIV/AIDS is one of the most serious public health challenges globally. Despite the great efforts that are being devoted to prevent,treat and to better understand the disease,it is one of the main causes of morbidity and mortality worldwide. Currently,there are 30 drugs or combinations of drugs approved by FDA. Because of the side-effects,price and drug resistance,it is essential to discover new targets,to develop new technology and to find new anti-HIV drugs. This review summarizes the major targets and assays currently used in anti-HIV drug screening.
基金supported by grants from the contract of China Petrochemical Corporation (3020001914-ZC0607-0013)the National Natural Science Foundation of China (20107073)+1 种基金the Guangdong Science and Technology Project (2014B030301030)the Innovative Research Team in University (No.IRT13078)
文摘Advanced analytical methodology based on comprehensive two-dimensional gas chromatography-time of flight mass spectrometry(GC×GC-TOFMS) is proposed for investigation of organic chlorides in different oilfield chemicals.The target screening was initially carried out on 8 suspected organic chlorides by evaluating the capability of the enhanced separation and reliable identification at a trace concentration. GC×GC-TOFMS allowed for the fast and automated analysis of organic chlorides at a level of 200 μg/L. This method was subsequently applied for non-target screening of organic chlorides in different oilfield chemicals at various locations across China. 22 organic chlorides were identified and verified by comparison with pure standards in the mixed sample. Finally, this method was used to determine the content of the organic chlorides in individual samples. The result showed that the organic chloride levels in 19 of the 39 tested oilfield chemicals were above the threshold limit of 1.0 mg/L.
文摘基于多靶点虚拟筛选、网络药理学分析和体外实验,探讨强肝胶囊(QGC)治疗非酒精性脂肪性肝病(NAFLD)的潜在作用机制。利用基于PPARα/γ、FXR及sEH的多靶点虚拟筛选选出QGC中具有治疗NAFLD的活性成分,运用网络药理学预测活性成分靶点、疾病相关靶点,筛选调控疾病的关键靶点,通过Discovery Studio 2020软件和Gromacs软件对关键活性成分和关键靶点进行分子对接和分子动力学模拟分析。最后,通过实验验证QGC中的关键活性成分对肝细胞脂肪变性的改善作用。多靶点虚拟筛选得到235个QGC活性成分,网络药理学分析得到320个成分-疾病共同靶点。分子对接结果表明,芹菜素、异鼠李素、迷迭香酸、大黄素甲醚、木犀草素与关键靶点PTPN1、PPARα、PPARγ、AR具有良好的结合能力。分子动力学模拟进一步验证了迷迭香酸、大黄素甲醚等化合物与关键靶点具有良好的结合稳定性。体外实验结果显示,5个关键活性成分均能改善HepG2细胞的脂肪变性,其中异鼠李素、迷迭香酸、大黄素甲醚改善细胞脂肪变性模型的效果最佳。本研究通过多层面探讨,为QGC在NAFLD治疗中的开发和应用提供理论依据。
