G-quadruplex(G4)is one of the higher-order DNA structures in guanine-rich sequences which are widely distributed across the genome.Due to their presence in oncogenic promoters and telomeres,G4 DNA structures become th...G-quadruplex(G4)is one of the higher-order DNA structures in guanine-rich sequences which are widely distributed across the genome.Due to their presence in oncogenic promoters and telomeres,G4 DNA structures become the novel targets in anticancer drug designs.Curaxin CBL0137,as an important candidate anticancer drug,can effectively inhibit the growth of multiple cancers.Although there is evidence that anticancer activity of curaxin is associated with its ability to bind DNA and to change the DNA topology,its therapeutic target and the underlying anti-cancer mechanism are still unclear.Here we show,for the first time,that curaxin CBL0137 induces G4 folding from anti-parallel to parallel structures,by single-molecule fluorescence resonance energy transfer technique.More importantly,we find that curaxin CBL0137 promotes G4 folding as well as stabilizes the folded G4 structures with long loops,giving a novel insight into effects of curaxin CBL0137 on DNA structures.Our work provides new ideas for the therapeutic mechanism of curaxin CBL0137 and for designs of new G4-targeting anticancer drugs.展开更多
针对膨胀土堑坡防护工程中不同的施工工序和降水入渗诱发灾害频发现象,基于原位孔内剪切试验,通过施加不同法向应力水平,以及成孔后注水浸泡等工况下的现场剪切试验,获得南阳某堑坡膨胀土强度特性随荷载施加方式与浸水条件的变化规律。...针对膨胀土堑坡防护工程中不同的施工工序和降水入渗诱发灾害频发现象,基于原位孔内剪切试验,通过施加不同法向应力水平,以及成孔后注水浸泡等工况下的现场剪切试验,获得南阳某堑坡膨胀土强度特性随荷载施加方式与浸水条件的变化规律。结果表明:膨胀土孔内剪切试验所得的剪应力-剪切位移曲线总体上呈现弱硬化变形特征;浸水对抗剪强度影响很大,最大降幅达56.9%,主要表现为黏聚力的降低,最大值达18.1 k Pa。预加载荷对浸水软化效应具有一定抑制作用,但当预加载荷超过某一应力水平时,难以发挥更大的抑制效果。黏聚力与预加载荷呈线性正相关;内摩擦角与预加载荷呈线性负相关,但降幅甚微。在实际工程中,膨胀土边坡稳定性分析应考虑降雨入渗对强度参数的影响,同时充分利用抗剪强度参数和预加载荷的线性关系,可根据工程要求达到的安全系数反推出所需的预加载荷大小,从而指导实际工程施工。该研究可为膨胀土工程场地评价、参数选取与灾害评价提供技术依据和参考。展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.10225417,21991133,12122402,and 12074043)the National Basic Research Program of China(Grant No.2006CB601003)。
文摘G-quadruplex(G4)is one of the higher-order DNA structures in guanine-rich sequences which are widely distributed across the genome.Due to their presence in oncogenic promoters and telomeres,G4 DNA structures become the novel targets in anticancer drug designs.Curaxin CBL0137,as an important candidate anticancer drug,can effectively inhibit the growth of multiple cancers.Although there is evidence that anticancer activity of curaxin is associated with its ability to bind DNA and to change the DNA topology,its therapeutic target and the underlying anti-cancer mechanism are still unclear.Here we show,for the first time,that curaxin CBL0137 induces G4 folding from anti-parallel to parallel structures,by single-molecule fluorescence resonance energy transfer technique.More importantly,we find that curaxin CBL0137 promotes G4 folding as well as stabilizes the folded G4 structures with long loops,giving a novel insight into effects of curaxin CBL0137 on DNA structures.Our work provides new ideas for the therapeutic mechanism of curaxin CBL0137 and for designs of new G4-targeting anticancer drugs.
基金国家自然科学基金重点项目(No.41430634)supported by the Key Program of National Nature Science Foundation of China(41430634)
文摘针对膨胀土堑坡防护工程中不同的施工工序和降水入渗诱发灾害频发现象,基于原位孔内剪切试验,通过施加不同法向应力水平,以及成孔后注水浸泡等工况下的现场剪切试验,获得南阳某堑坡膨胀土强度特性随荷载施加方式与浸水条件的变化规律。结果表明:膨胀土孔内剪切试验所得的剪应力-剪切位移曲线总体上呈现弱硬化变形特征;浸水对抗剪强度影响很大,最大降幅达56.9%,主要表现为黏聚力的降低,最大值达18.1 k Pa。预加载荷对浸水软化效应具有一定抑制作用,但当预加载荷超过某一应力水平时,难以发挥更大的抑制效果。黏聚力与预加载荷呈线性正相关;内摩擦角与预加载荷呈线性负相关,但降幅甚微。在实际工程中,膨胀土边坡稳定性分析应考虑降雨入渗对强度参数的影响,同时充分利用抗剪强度参数和预加载荷的线性关系,可根据工程要求达到的安全系数反推出所需的预加载荷大小,从而指导实际工程施工。该研究可为膨胀土工程场地评价、参数选取与灾害评价提供技术依据和参考。
