GB7 acetate is a galbulimima alkaloid obtained from Galbulimima belgraveana.However,information regarding its structure,biological activities,and related mechanisms is not entirely available.A series of spectroscopic ...GB7 acetate is a galbulimima alkaloid obtained from Galbulimima belgraveana.However,information regarding its structure,biological activities,and related mechanisms is not entirely available.A series of spectroscopic analyses,structural degradation,interconversion,and crystallography were performed to identify the structure of GB7 acetate.The MTT assay was applied to measure cell proliferation on human colorectal cancer HCT 116 cells.The expressions of the related proteins were measured by Western blotting.Transmission electron microscopy(TEM),acridine orange(AO)and monodansylcadaverine(MDC)staining were used to detect the presence of autophagic vesicles and autolysosomes.A transwell assay was performed to demonstrate metastatic capabilities.Oxygen consumption rate(OCR)and extracellular acidification rate(ECAR)assays were performed to determine the mitochondrial oxidative phosphorylation(OXPHOS)and glycolysis activity of HCT 116 cells.The data showed that GB7 acetate suppressed the proliferation and colony-forming ability of HCT 116 cells.Pretreatment with GB7 acetate significantly induced the formation of autophagic vesicles and autolysosomes.GB7 acetate upregulated the expressions of LC3 and Thr172 phosphorylated adenosine 5'-monophosphate(AMP)-activated protein kinase a(p-AMPKa),which are key elements of autophagy.In addition,GB7 acetate suppressed the metastatic capabilities of HCT 116 cells.Additionally,the production of matrix metallo-proteinase-2(MMP-2)and MMP-9 was reduced,whereas the expression of E-cadherin(E-cad)was upregulated.Furthermore,GB7 acetate significantly reduced mitochondrial OXPHOS and glycolysis.In conclusion,the structure of the novel Galbulimima alkaloid GB7 acetate was identified.GB7 acetate was shown to have anti-proliferative,pro-autophagic,anti-metastatic,and anti-metabolite capabilities in HCT 116 cells.This study might provide new insights into cancer treatment efficacy and cancer chemoprevention.展开更多
国际电工委员会于2008年颁布IEC 60335-2-7:2008(Ed7.0),Household and similar electrical appliances Safety Part 2-7:Particular requirements for washing machine,我国将该标准修改采用为国标GB 4706.24-2008《家用和类似用途的...国际电工委员会于2008年颁布IEC 60335-2-7:2008(Ed7.0),Household and similar electrical appliances Safety Part 2-7:Particular requirements for washing machine,我国将该标准修改采用为国标GB 4706.24-2008《家用和类似用途的安全洗衣机的特殊要求》。后续,国际电工委在2011年和2016年分别颁布了该版本的A1和A2增补件。本文探讨和比较了最新版IEC 60335-2-7:2016和GB 4706.24-2008的主要差异。展开更多
目的 观察针刺百会、曲鬓穴对急性期脑出血(ICH)大鼠白细胞分化抗原36(CD36)、Toll样受体4(TLR4)表达的影响,探讨针刺治疗脑出血的作用机制。方法 选择144只Wistar雄性大鼠,采用随机数字表法分为假手术组、模型组、针刺组、抑制剂组4组...目的 观察针刺百会、曲鬓穴对急性期脑出血(ICH)大鼠白细胞分化抗原36(CD36)、Toll样受体4(TLR4)表达的影响,探讨针刺治疗脑出血的作用机制。方法 选择144只Wistar雄性大鼠,采用随机数字表法分为假手术组、模型组、针刺组、抑制剂组4组,每组36只,每组按1、3、7 d时间点再分为3个亚组,每组12只。采用立体定位自体血注入法建立ICH大鼠模型。模型组仅接受ICH模型制备,不进行任何治疗;假手术组接受类似模型组各项手术操作,但不进行注血制作;抑制剂组造模后6 h,腹腔注射TLR4抑制剂TAK242,3 mg/kg,1次/d,连续5 d;造模12 h后,针刺组各亚组开始接受针刺治疗,穴位选择百会穴(顶骨正中)、右侧曲鬓穴,采用透刺方法,进针深度20 mm,以100 r/min小幅度捻转,持续捻转2 min,每间隔5 min捻针1次,共留针30 min,期间捻转3次,1次/d,针刺组各亚组分别治疗1、3、7 d。分别于治疗后第1、3、7天,采用改良神经功能缺损评分(mNSS)评估大鼠神经功能;检测脑组织血肿体积;采用Western blot法检测脑组织CD36、TLR4蛋白表达水平;采用免疫荧光法观察CD36、TLR4在星形胶质细胞中的表达。结果 (1) mNSS评分:与假手术组同一时间点比较,模型组、针刺组、抑制剂组治疗后1、3、7 d mNSS评分均明显升高(P<0.05);与模型组同一时间点比较,针刺组、抑制剂组治疗后1、3、7 d mNSS评分均明显降低(P<0.05);与针刺组同一时间点比较,抑制剂组治疗后1 d mNSS评分明显降低(P<0.05)。(2)血肿体积:与模型组同一时间点比较,针刺组、抑制剂组治疗后3、7 d脑血肿体积均明显降低,抑制剂组治疗后1、3、7 d脑血肿体积明显降低(P<0.05);与针刺组同一时间点比较,抑制剂组治疗后1、3、7 d脑血肿体积明显降低(P<0.05)。(3) CD36、TLR4蛋白表达水平:与假手术组同一时间点比较,模型组、针刺组、抑制剂组治疗后1、3、7 d CD36、TLR4蛋白表达水平均明显升高(P<0.05);与模型组同一时间点比较,针刺组、抑制剂组治疗后1、3、7 d CD36蛋白表达水平均明显升高(P<0.05),针刺组、抑制剂组治疗后3、7 d TLR4蛋白表达水平均明显降低(P<0.05);与针刺组比较,抑制剂组治疗后1、3、7 d CD36蛋白表达水平均明显升高,TLR4蛋白表达水平均明显降低(P<0.05)。(4) CD36、TLR4在GFAP中的表达水平:假手术组大鼠脑组织内可见少量CD36、TLR4表达。与假手术组同一时间点比较,模型组治疗后1、3、7 d CD36、TLR4在GFAP表达均明显增加(P<0.05);与模型组同一时间点比较,抑制剂组、针刺组治疗后1、3、7 d CD36在GFAP表达明显增加,TLR4在GFAP表达明显降低(P<0.05)。结论 针刺百会、曲鬓穴可以改善急性期ICH大鼠神经功能,减轻脑出血血肿体积,可能与促进CD36蛋白表达、抑制TLR4蛋白表达有关。展开更多
本文探讨了IEC 60335-2-7:2008《Household and similar electrical appliances Safety Part 2-7:Particular requirements for Washing machines》和GB 4706.24-2008《家用和类似用途电器的安全洗衣机的特殊要求》中条款20.101和20.10...本文探讨了IEC 60335-2-7:2008《Household and similar electrical appliances Safety Part 2-7:Particular requirements for Washing machines》和GB 4706.24-2008《家用和类似用途电器的安全洗衣机的特殊要求》中条款20.101和20.103对全自动波轮式洗衣机的适用性问题,并通过分析实际案例中存在的安全隐患,进一步说明条款20.101和20.103适用于全自动波轮式洗衣机的重要性。同时本文还介绍了IEC/TC61国际电工委员会家用电器技术委员会在标准IEC 60335-2-7机械危险方面制修订的最新动态。展开更多
The conformational scan of anti-HIV peptide T22 ([Tyr5,12, Lys7]-polyphemusin II) backbone on a deformed potential energy surface (PES) was performed using the potential smoothing searching (PSS) protocol. All located...The conformational scan of anti-HIV peptide T22 ([Tyr5,12, Lys7]-polyphemusin II) backbone on a deformed potential energy surface (PES) was performed using the potential smoothing searching (PSS) protocol. All located minima were then transferred to the original PES using undeformed optimized potentials for liquid simulations (OPLS) potential function, and minimized by multi-con-former minimization (MCM). For solution-phase calculations, the GB/SA continuum model for water was used. This application of PSS integrated with MCM is proved a feasible method for solving the multiple-minimum problem in the conformational analysis of flexible molecules with cyclic structure.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.:81773429)2017 High Level University Program Research Foundation for Advanced Talents(Grant No.:C1034220)Guangdong Natural Science Foundation(Grant No.:2020A1515010594)。
文摘GB7 acetate is a galbulimima alkaloid obtained from Galbulimima belgraveana.However,information regarding its structure,biological activities,and related mechanisms is not entirely available.A series of spectroscopic analyses,structural degradation,interconversion,and crystallography were performed to identify the structure of GB7 acetate.The MTT assay was applied to measure cell proliferation on human colorectal cancer HCT 116 cells.The expressions of the related proteins were measured by Western blotting.Transmission electron microscopy(TEM),acridine orange(AO)and monodansylcadaverine(MDC)staining were used to detect the presence of autophagic vesicles and autolysosomes.A transwell assay was performed to demonstrate metastatic capabilities.Oxygen consumption rate(OCR)and extracellular acidification rate(ECAR)assays were performed to determine the mitochondrial oxidative phosphorylation(OXPHOS)and glycolysis activity of HCT 116 cells.The data showed that GB7 acetate suppressed the proliferation and colony-forming ability of HCT 116 cells.Pretreatment with GB7 acetate significantly induced the formation of autophagic vesicles and autolysosomes.GB7 acetate upregulated the expressions of LC3 and Thr172 phosphorylated adenosine 5'-monophosphate(AMP)-activated protein kinase a(p-AMPKa),which are key elements of autophagy.In addition,GB7 acetate suppressed the metastatic capabilities of HCT 116 cells.Additionally,the production of matrix metallo-proteinase-2(MMP-2)and MMP-9 was reduced,whereas the expression of E-cadherin(E-cad)was upregulated.Furthermore,GB7 acetate significantly reduced mitochondrial OXPHOS and glycolysis.In conclusion,the structure of the novel Galbulimima alkaloid GB7 acetate was identified.GB7 acetate was shown to have anti-proliferative,pro-autophagic,anti-metastatic,and anti-metabolite capabilities in HCT 116 cells.This study might provide new insights into cancer treatment efficacy and cancer chemoprevention.
文摘国际电工委员会于2008年颁布IEC 60335-2-7:2008(Ed7.0),Household and similar electrical appliances Safety Part 2-7:Particular requirements for washing machine,我国将该标准修改采用为国标GB 4706.24-2008《家用和类似用途的安全洗衣机的特殊要求》。后续,国际电工委在2011年和2016年分别颁布了该版本的A1和A2增补件。本文探讨和比较了最新版IEC 60335-2-7:2016和GB 4706.24-2008的主要差异。
文摘目的 观察针刺百会、曲鬓穴对急性期脑出血(ICH)大鼠白细胞分化抗原36(CD36)、Toll样受体4(TLR4)表达的影响,探讨针刺治疗脑出血的作用机制。方法 选择144只Wistar雄性大鼠,采用随机数字表法分为假手术组、模型组、针刺组、抑制剂组4组,每组36只,每组按1、3、7 d时间点再分为3个亚组,每组12只。采用立体定位自体血注入法建立ICH大鼠模型。模型组仅接受ICH模型制备,不进行任何治疗;假手术组接受类似模型组各项手术操作,但不进行注血制作;抑制剂组造模后6 h,腹腔注射TLR4抑制剂TAK242,3 mg/kg,1次/d,连续5 d;造模12 h后,针刺组各亚组开始接受针刺治疗,穴位选择百会穴(顶骨正中)、右侧曲鬓穴,采用透刺方法,进针深度20 mm,以100 r/min小幅度捻转,持续捻转2 min,每间隔5 min捻针1次,共留针30 min,期间捻转3次,1次/d,针刺组各亚组分别治疗1、3、7 d。分别于治疗后第1、3、7天,采用改良神经功能缺损评分(mNSS)评估大鼠神经功能;检测脑组织血肿体积;采用Western blot法检测脑组织CD36、TLR4蛋白表达水平;采用免疫荧光法观察CD36、TLR4在星形胶质细胞中的表达。结果 (1) mNSS评分:与假手术组同一时间点比较,模型组、针刺组、抑制剂组治疗后1、3、7 d mNSS评分均明显升高(P<0.05);与模型组同一时间点比较,针刺组、抑制剂组治疗后1、3、7 d mNSS评分均明显降低(P<0.05);与针刺组同一时间点比较,抑制剂组治疗后1 d mNSS评分明显降低(P<0.05)。(2)血肿体积:与模型组同一时间点比较,针刺组、抑制剂组治疗后3、7 d脑血肿体积均明显降低,抑制剂组治疗后1、3、7 d脑血肿体积明显降低(P<0.05);与针刺组同一时间点比较,抑制剂组治疗后1、3、7 d脑血肿体积明显降低(P<0.05)。(3) CD36、TLR4蛋白表达水平:与假手术组同一时间点比较,模型组、针刺组、抑制剂组治疗后1、3、7 d CD36、TLR4蛋白表达水平均明显升高(P<0.05);与模型组同一时间点比较,针刺组、抑制剂组治疗后1、3、7 d CD36蛋白表达水平均明显升高(P<0.05),针刺组、抑制剂组治疗后3、7 d TLR4蛋白表达水平均明显降低(P<0.05);与针刺组比较,抑制剂组治疗后1、3、7 d CD36蛋白表达水平均明显升高,TLR4蛋白表达水平均明显降低(P<0.05)。(4) CD36、TLR4在GFAP中的表达水平:假手术组大鼠脑组织内可见少量CD36、TLR4表达。与假手术组同一时间点比较,模型组治疗后1、3、7 d CD36、TLR4在GFAP表达均明显增加(P<0.05);与模型组同一时间点比较,抑制剂组、针刺组治疗后1、3、7 d CD36在GFAP表达明显增加,TLR4在GFAP表达明显降低(P<0.05)。结论 针刺百会、曲鬓穴可以改善急性期ICH大鼠神经功能,减轻脑出血血肿体积,可能与促进CD36蛋白表达、抑制TLR4蛋白表达有关。
文摘本文探讨了IEC 60335-2-7:2008《Household and similar electrical appliances Safety Part 2-7:Particular requirements for Washing machines》和GB 4706.24-2008《家用和类似用途电器的安全洗衣机的特殊要求》中条款20.101和20.103对全自动波轮式洗衣机的适用性问题,并通过分析实际案例中存在的安全隐患,进一步说明条款20.101和20.103适用于全自动波轮式洗衣机的重要性。同时本文还介绍了IEC/TC61国际电工委员会家用电器技术委员会在标准IEC 60335-2-7机械危险方面制修订的最新动态。
基金Sun Ming thanks Prof. Ponder, J. W. and Prof. Nikiforovich, G. V. in Washington University for helpful discussions, and Prof. Garland Marshall and the Chinese State Scholarship Council for support.
文摘The conformational scan of anti-HIV peptide T22 ([Tyr5,12, Lys7]-polyphemusin II) backbone on a deformed potential energy surface (PES) was performed using the potential smoothing searching (PSS) protocol. All located minima were then transferred to the original PES using undeformed optimized potentials for liquid simulations (OPLS) potential function, and minimized by multi-con-former minimization (MCM). For solution-phase calculations, the GB/SA continuum model for water was used. This application of PSS integrated with MCM is proved a feasible method for solving the multiple-minimum problem in the conformational analysis of flexible molecules with cyclic structure.
