目的利用计算机模拟技术探索具有增敏紫杉醇、阿霉素等药物抗肿瘤作用的天然C21甾体酯类化合物11α-O-苯甲酰-12β-O-乙酰-通光散苷元乙(BAT)的抗肿瘤增效作用的分子靶点。方法基于计算机虚拟技术,以BAT作为配体,选取14个具有晶体结构...目的利用计算机模拟技术探索具有增敏紫杉醇、阿霉素等药物抗肿瘤作用的天然C21甾体酯类化合物11α-O-苯甲酰-12β-O-乙酰-通光散苷元乙(BAT)的抗肿瘤增效作用的分子靶点。方法基于计算机虚拟技术,以BAT作为配体,选取14个具有晶体结构的细胞色素P450(CYP)代谢酶作为受体蛋白;采用SYBYL分子对接方法,以Total-Score和C-Score打分为标准,筛选出打分最高的蛋白;观察其MOLCAD展示的蛋白的表面疏水区域和氢键供体与受体区域,借助Discovery Studio 2016版软件分析其相互作用力,预测两者间的结合模式。将BAT/阳性对照(酮康唑)与肝微粒体CYP3A4及探针底物共孵育,采用LC/MS技术分析BAT对酶活性的影响。结果分子对接分析可见BAT与5个靶蛋白CYP3A4、CYP1B1、CYP2C8、CYP2D6和CYP2E1结合,具有较高的Total-Score和C-Score打分值;BAT可以通过多种分子间作用力稳定地结合在受体蛋白的活性位点。体外生物活性试验表明,BAT对肝微粒体CYP3A4呈较强抑制作用,以睾酮为底物的半数抑制浓度IC_(50)为0.61μmol·L^(-1)(加NADPH)或1.66μmol·L^(-1)(不加NADPH)。结论基于分子对接技术分析,C_(21)甾体酯类化合物BAT能够与5种CYP结合,调节其酶活性,影响作为代谢酶底物的紫杉醇、阿霉素等抗肿瘤药物的代谢,对肿瘤化疗药物的药效产生影响。生物活性实验证实了BAT对CYP3A4的显著抑制作用。展开更多
This work was attempted to modify the current technology for thermal barrier coatings（TBCs） by adding an additional step of surface modification,namely,supersonic fine particles bombarding（SFPB） process,on bond co...This work was attempted to modify the current technology for thermal barrier coatings（TBCs） by adding an additional step of surface modification,namely,supersonic fine particles bombarding（SFPB） process,on bond coat before applying the topcoat.After isothermal oxidation at 1000 °C for different time,the surface state of the bond coat and its phase transformation were investigated using X-ray diffraction（XRD）,scanning electron microscopy（SEM） equipped with energy-dispersive X-ray spectrometry（EDS）,transmission electron microscopy（TEM） and Cr3＋ luminescence spectroscopy.The dislocation density significantly increases after SFPB process,which can generate a large number of diffusion channels in the area of the surface of the bond coat.At the initial stage of isothermal oxidation,the diffusion velocity of Al in the bond coat significantly increases,leading to the formation of a layer of stable α-Al2O3 phase.A great number of Cr3＋ positive ions can diffuse via diffusion channels during the transient state of isothermal oxidation,which can lead to the presence of（Al0.9Cr0.1）2O3 phase and accelerate the γ→θ→α phase transformation.Cr3＋ luminescence spectroscopy measurement shows that the residual stress increases at the initial stage of isothermal oxidation and then decreases.The residual stress after isothermal oxidation for 310 h reduces to 0.63 GPa compared with 0.93 GPa after isothermal oxidation for 26 h.In order to prolong the lifespan of TBCs,a layer of continuous,dense and pure α-Al2O3 with high oxidation resistance at the interface between topcoat and bond coat can be obtained due to additional SFPB process.展开更多
This paper presents an approach to calculate dispersion penalty for VSR-1 optical links.Based on parameters of a specific VSR-1 link,dispersion penalties are computed for various modal dispersion bandwidths respective...This paper presents an approach to calculate dispersion penalty for VSR-1 optical links.Based on parameters of a specific VSR-1 link,dispersion penalties are computed for various modal dispersion bandwidths respectively.The worst-case eye closure is expressed numerically by using the signal waveform at time 0,and the signal waveform is obtained in frequency domain through FFT algorithm.By this approach,the dispersion penalty is determined by the shape of transfer functions of the various components in the links.To simplify the derivation of multimode fiber link transfer function,a Gaussian form of normalized impulse response is used.This calculation approach can be used to estimate the worst-case dispersion penalty of VSR-1 links in the link budget analysis.展开更多
文摘目的利用计算机模拟技术探索具有增敏紫杉醇、阿霉素等药物抗肿瘤作用的天然C21甾体酯类化合物11α-O-苯甲酰-12β-O-乙酰-通光散苷元乙(BAT)的抗肿瘤增效作用的分子靶点。方法基于计算机虚拟技术,以BAT作为配体,选取14个具有晶体结构的细胞色素P450(CYP)代谢酶作为受体蛋白;采用SYBYL分子对接方法,以Total-Score和C-Score打分为标准,筛选出打分最高的蛋白;观察其MOLCAD展示的蛋白的表面疏水区域和氢键供体与受体区域,借助Discovery Studio 2016版软件分析其相互作用力,预测两者间的结合模式。将BAT/阳性对照(酮康唑)与肝微粒体CYP3A4及探针底物共孵育,采用LC/MS技术分析BAT对酶活性的影响。结果分子对接分析可见BAT与5个靶蛋白CYP3A4、CYP1B1、CYP2C8、CYP2D6和CYP2E1结合,具有较高的Total-Score和C-Score打分值;BAT可以通过多种分子间作用力稳定地结合在受体蛋白的活性位点。体外生物活性试验表明,BAT对肝微粒体CYP3A4呈较强抑制作用,以睾酮为底物的半数抑制浓度IC_(50)为0.61μmol·L^(-1)(加NADPH)或1.66μmol·L^(-1)(不加NADPH)。结论基于分子对接技术分析,C_(21)甾体酯类化合物BAT能够与5种CYP结合,调节其酶活性,影响作为代谢酶底物的紫杉醇、阿霉素等抗肿瘤药物的代谢,对肿瘤化疗药物的药效产生影响。生物活性实验证实了BAT对CYP3A4的显著抑制作用。
基金Foundation item: Project (50575220) supported by the National Natural Science Foundation of ChinaProject supported by State Key Laboratory of Engines,China
文摘This work was attempted to modify the current technology for thermal barrier coatings（TBCs） by adding an additional step of surface modification,namely,supersonic fine particles bombarding（SFPB） process,on bond coat before applying the topcoat.After isothermal oxidation at 1000 °C for different time,the surface state of the bond coat and its phase transformation were investigated using X-ray diffraction（XRD）,scanning electron microscopy（SEM） equipped with energy-dispersive X-ray spectrometry（EDS）,transmission electron microscopy（TEM） and Cr3＋ luminescence spectroscopy.The dislocation density significantly increases after SFPB process,which can generate a large number of diffusion channels in the area of the surface of the bond coat.At the initial stage of isothermal oxidation,the diffusion velocity of Al in the bond coat significantly increases,leading to the formation of a layer of stable α-Al2O3 phase.A great number of Cr3＋ positive ions can diffuse via diffusion channels during the transient state of isothermal oxidation,which can lead to the presence of（Al0.9Cr0.1）2O3 phase and accelerate the γ→θ→α phase transformation.Cr3＋ luminescence spectroscopy measurement shows that the residual stress increases at the initial stage of isothermal oxidation and then decreases.The residual stress after isothermal oxidation for 310 h reduces to 0.63 GPa compared with 0.93 GPa after isothermal oxidation for 26 h.In order to prolong the lifespan of TBCs,a layer of continuous,dense and pure α-Al2O3 with high oxidation resistance at the interface between topcoat and bond coat can be obtained due to additional SFPB process.
基金Supported by"863"Hi-Tech Research and Development Program(2005AA311030) and the National Natural Science Foundationof China(Grant No.60502005)
文摘This paper presents an approach to calculate dispersion penalty for VSR-1 optical links.Based on parameters of a specific VSR-1 link,dispersion penalties are computed for various modal dispersion bandwidths respectively.The worst-case eye closure is expressed numerically by using the signal waveform at time 0,and the signal waveform is obtained in frequency domain through FFT algorithm.By this approach,the dispersion penalty is determined by the shape of transfer functions of the various components in the links.To simplify the derivation of multimode fiber link transfer function,a Gaussian form of normalized impulse response is used.This calculation approach can be used to estimate the worst-case dispersion penalty of VSR-1 links in the link budget analysis.
