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基于代谢组学的多西他赛调控肺癌细胞代谢重编程研究 被引量:5
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作者 孙海超 朴海龙 +2 位作者 齐欢 颜敏 刘宏旭 《中国肺癌杂志》 CAS CSCD 北大核心 2019年第4期208-215,共8页
背景与目的多西他赛是一种临床常用的抗肿瘤药物,是晚期非小细胞肺癌(non-small cell lung cancer, NSCLC)的一线用药。然而,多西他赛抗NSCLC作用的分子机制尚不明确。研究表明肿瘤细胞的代谢重编程在肿瘤发生发展过程中发挥重要作用。... 背景与目的多西他赛是一种临床常用的抗肿瘤药物,是晚期非小细胞肺癌(non-small cell lung cancer, NSCLC)的一线用药。然而,多西他赛抗NSCLC作用的分子机制尚不明确。研究表明肿瘤细胞的代谢重编程在肿瘤发生发展过程中发挥重要作用。本研究旨在通过结合代谢组学分析及生物学手段来探讨多西他赛所影响的NSCLC细胞代谢通路。方法首先,通过CCK-8实验分析多西他赛对NSCLC细胞活力的影响,筛选合适药物浓度。接下来,通过基于气相色谱质谱联用(gas chromatography-mass spectrometry, GC-MS)的代谢组学技术分析多西他赛处理和未处理的A549和H1299细胞。并通过统计学计算得到处理组和未处理组间的差异代谢物。最后,通过蛋白质免疫印迹分析(Western blot)多西他赛对其所调控的相关代谢途径中关键酶蛋白质表达水平的影响。结果多西他赛可时间依赖和浓度依赖地抑制A549和H1299细胞活力。随着多西他赛处理时间延长,凋亡敏感蛋白质多聚二磷酸腺苷核糖聚合酶[Poly(ADP-)Polymerase, PARP]逐渐被激活裂解形成P89片段。代谢组学分析发现,药物处理后的A549和H1299细胞内,8种代谢物均发生显著变化,主要集中于三羧酸(tricarboxylic acid, TCA)循环代谢通路。同时,药物处理后,TCA循环关键调控酶异柠檬酸脱氢酶蛋白质表达水平显著下降。结论多西他赛诱导NSCLC增殖抑制及凋亡的效应可能与下调异柠檬酸脱氢酶,进而抑制三羧酸循环代谢途径有关。 展开更多
关键词 多西他赛 肺肿瘤 气相色谱质谱联用 代谢组学 三羧酸循环
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Serration and shear avalanches in a ZrCu based bulk metallic glass composite in different loading methods
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作者 haichao sun Zhiliang Ning +5 位作者 Jingli Ren Weizhong Liang Yongjiang Huang Jianfei sun Xiang Xue Gang Wang 《Journal of Materials Science & Technology》 SCIE EI CAS CSCD 2019年第9期2079-2085,共7页
In the current research, serrated flow is investigated under tensile and compressive loading in a ZrCubased bulk metallic glass composite (BMGC) that is well known for its plastic deformability, which is higher than t... In the current research, serrated flow is investigated under tensile and compressive loading in a ZrCubased bulk metallic glass composite (BMGC) that is well known for its plastic deformability, which is higher than that of metallic glasses. Statistical analysis on serrations shows a complex, scale free process, in which shear bands are highly correlated. The distribution of the elastic-energy density stored in each serration event follows a power-law relationship, showing a randomly generated serrated event under both tension and compression tests. The plastic deformation in the temporal space is explored by a timeseries analysis, which is consistent with the trajectory convergent evolution in critical dynamic behavior even in the low strain rate regime in both tests. The results demonstrate that the secondary phase in the BMGC can stabilize the shear band extension and facilitate the critical behavior in the low strain rate regime. This study provides a strong evidence of serrated flow phenomenon in BMGC under tension test, and offers a deep understanding of the correlation between serrations and shear banding in temporal space. 展开更多
关键词 METALLIC GLASS Bulk METALLIC GLASS composites Serrated flow SHEAR AVALANCHES Statistical analysis Critical behavior
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