目的探究CDP-二酰基甘油合酶1(CDS1)对小鼠海马神经细胞自噬和淀粉样蛋白沉积的影响及机制。方法使用刚果红和免疫组织化学染色观察淀粉样前体蛋白(APP)/早老蛋白1(PS1)双转基因小鼠海马组织淀粉样物质的沉积情况;慢病毒介导HT22细胞内...目的探究CDP-二酰基甘油合酶1(CDS1)对小鼠海马神经细胞自噬和淀粉样蛋白沉积的影响及机制。方法使用刚果红和免疫组织化学染色观察淀粉样前体蛋白(APP)/早老蛋白1(PS1)双转基因小鼠海马组织淀粉样物质的沉积情况;慢病毒介导HT22细胞内APP过表达,刚果红染色观察细胞内淀粉样物质沉积情况;蛋白质印迹法检测APP/PS1双转基因小鼠海马组织和APP过表达HT22细胞的微管相关蛋白1轻链3(LC3)-Ⅱ、P62蛋白表达情况;通过APP/PS1双转基因小鼠海马蛋白质组学结果,筛选出差异表达蛋白CDS1;蛋白质印迹法检测APP/PS1双转基因小鼠海马组织和APP过表达HT22细胞中的CDS1蛋白表达情况;慢病毒介导HT22细胞APP过表达后,再过表达CDS1,采用蛋白质印迹法检测LC3-Ⅱ、P62蛋白表达情况。结果APP/PS1双转基因小鼠海马组织及APP过表达HT22细胞中均有β-淀粉样蛋白的沉积。在APP/PS1双转基因小鼠海马组织和APP过表达HT22细胞中LC3-Ⅱ、P62蛋白均升高。从APP/PS1双转基因小鼠蛋白质组学结果中的京都基因与基因组百科全书通路分析筛选到其中一条差异代谢通路——甘油磷脂代谢通路,从该通路中获取到差异表达蛋白CDS1。与野生型C57BL/6小鼠相比,APP/PS1双转基因小鼠海马组织中CDS1蛋白表达量下降(0.46±0.07 vs 1.00±0.25,P<0.01);与感染空载病毒载体的HT22细胞相比,慢病毒过表达APP的HT22细胞中CDS1蛋白表达量下降(0.68±0.18 vs 1.00±0.13,P<0.01)。在APP过表达的HT22细胞过表达CDS1后,神经细胞的自噬流明显恢复(LC3-Ⅱ:1.00±0.15 vs 0.21±0.05,P<0.01;P62:1.00±0.16 vs 0.67±0.10,P<0.01),并且Aβ沉积明显减少。结论CDS1表达下调诱导自噬体与溶酶体融合障碍,促进阿尔茨海默病小鼠海马淀粉样物质沉积。展开更多
The α-acetyl ketene dithioacetals 2, which bear various alkylthio groups, are a kind of important intermediates in organic synthesis. In this paper, dithioacetals 2 were prepared in very high yields (90%—100%) via t...The α-acetyl ketene dithioacetals 2, which bear various alkylthio groups, are a kind of important intermediates in organic synthesis. In this paper, dithioacetals 2 were prepared in very high yields (90%—100%) via the deacetylation reaction of the corresponding α,α-diacetyl ketene dithioacetals 1 in the presence of concentrated sulfuric acid. This reaction involves an %in-situ% electrophilic addition-deacetylation mechanism and shows the nucleophilicity of the α-carbon atom in α-oxo ketenedithioacetals. Meanwhile, when the reaction time was prolonged to 22—25 h, the β-keto thiolesters 3a and 3c were produced in good yields.展开更多
As a kind of versatile synthons, α-oxoketene dithioacetals have found their wide utilizations in organic synthesis. Owing to the interaction between two electron donating groups(RS) and an electron withdrawing group ...As a kind of versatile synthons, α-oxoketene dithioacetals have found their wide utilizations in organic synthesis. Owing to the interaction between two electron donating groups(RS) and an electron withdrawing group in the α position, the α-carbon atom of α-EWG ketene S,S-acetals shows a high nucleophilicity. In this paper, the reactions of α-acetyl cyclic ketendithioacetals with a series of acyl chlorides were performed and a new route to the C～C bond formation reaction at the α-carbon atom of α-oxoketene dithioacetals was described. By the above reactions, α-acetyl-α-acyl ketendithioacetals were prepared with good to high yields(55%～82%) via the acylation of α-acetyl cyclic ketendithioacetals at the α-carbon atom of α-acetyl ketendithioacetals mediated by titanium tetrachloride in dry dichloromethane at reflux temperature. The mechanism of the acylation between compound 1 and acyl chloride was proposed, which belongs to nucleophilic addition-elimination reaction.展开更多
The nonlinear optical properties of a series of compounds of 1-benzoyl-3-substituted phenyl thiourea derivatives were theoreticaly studied.On the basis given above,their nonlinear optical properties were investigated....The nonlinear optical properties of a series of compounds of 1-benzoyl-3-substituted phenyl thiourea derivatives were theoreticaly studied.On the basis given above,their nonlinear optical properties were investigated.We speculate that these compounds have applied potentials as nonlinear optical materials.展开更多
文摘目的探究CDP-二酰基甘油合酶1(CDS1)对小鼠海马神经细胞自噬和淀粉样蛋白沉积的影响及机制。方法使用刚果红和免疫组织化学染色观察淀粉样前体蛋白(APP)/早老蛋白1(PS1)双转基因小鼠海马组织淀粉样物质的沉积情况;慢病毒介导HT22细胞内APP过表达,刚果红染色观察细胞内淀粉样物质沉积情况;蛋白质印迹法检测APP/PS1双转基因小鼠海马组织和APP过表达HT22细胞的微管相关蛋白1轻链3(LC3)-Ⅱ、P62蛋白表达情况;通过APP/PS1双转基因小鼠海马蛋白质组学结果,筛选出差异表达蛋白CDS1;蛋白质印迹法检测APP/PS1双转基因小鼠海马组织和APP过表达HT22细胞中的CDS1蛋白表达情况;慢病毒介导HT22细胞APP过表达后,再过表达CDS1,采用蛋白质印迹法检测LC3-Ⅱ、P62蛋白表达情况。结果APP/PS1双转基因小鼠海马组织及APP过表达HT22细胞中均有β-淀粉样蛋白的沉积。在APP/PS1双转基因小鼠海马组织和APP过表达HT22细胞中LC3-Ⅱ、P62蛋白均升高。从APP/PS1双转基因小鼠蛋白质组学结果中的京都基因与基因组百科全书通路分析筛选到其中一条差异代谢通路——甘油磷脂代谢通路,从该通路中获取到差异表达蛋白CDS1。与野生型C57BL/6小鼠相比,APP/PS1双转基因小鼠海马组织中CDS1蛋白表达量下降(0.46±0.07 vs 1.00±0.25,P<0.01);与感染空载病毒载体的HT22细胞相比,慢病毒过表达APP的HT22细胞中CDS1蛋白表达量下降(0.68±0.18 vs 1.00±0.13,P<0.01)。在APP过表达的HT22细胞过表达CDS1后,神经细胞的自噬流明显恢复(LC3-Ⅱ:1.00±0.15 vs 0.21±0.05,P<0.01;P62:1.00±0.16 vs 0.67±0.10,P<0.01),并且Aβ沉积明显减少。结论CDS1表达下调诱导自噬体与溶酶体融合障碍,促进阿尔茨海默病小鼠海马淀粉样物质沉积。
文摘The α-acetyl ketene dithioacetals 2, which bear various alkylthio groups, are a kind of important intermediates in organic synthesis. In this paper, dithioacetals 2 were prepared in very high yields (90%—100%) via the deacetylation reaction of the corresponding α,α-diacetyl ketene dithioacetals 1 in the presence of concentrated sulfuric acid. This reaction involves an %in-situ% electrophilic addition-deacetylation mechanism and shows the nucleophilicity of the α-carbon atom in α-oxo ketenedithioacetals. Meanwhile, when the reaction time was prolonged to 22—25 h, the β-keto thiolesters 3a and 3c were produced in good yields.
文摘As a kind of versatile synthons, α-oxoketene dithioacetals have found their wide utilizations in organic synthesis. Owing to the interaction between two electron donating groups(RS) and an electron withdrawing group in the α position, the α-carbon atom of α-EWG ketene S,S-acetals shows a high nucleophilicity. In this paper, the reactions of α-acetyl cyclic ketendithioacetals with a series of acyl chlorides were performed and a new route to the C～C bond formation reaction at the α-carbon atom of α-oxoketene dithioacetals was described. By the above reactions, α-acetyl-α-acyl ketendithioacetals were prepared with good to high yields(55%～82%) via the acylation of α-acetyl cyclic ketendithioacetals at the α-carbon atom of α-acetyl ketendithioacetals mediated by titanium tetrachloride in dry dichloromethane at reflux temperature. The mechanism of the acylation between compound 1 and acyl chloride was proposed, which belongs to nucleophilic addition-elimination reaction.
文摘The nonlinear optical properties of a series of compounds of 1-benzoyl-3-substituted phenyl thiourea derivatives were theoreticaly studied.On the basis given above,their nonlinear optical properties were investigated.We speculate that these compounds have applied potentials as nonlinear optical materials.
