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Cho-Yi Chen Masaoki Kawasumi Tien-Yun Lan Chi-Lam Poon Yi-Sian Lin Pin-Jou Wu Yao-Chung Chen Bing-Hong Chen Cheng-Hsien Wu Jeng-Fan Lo Rueyhung Roc Weng Yi-Chen Sun Kai-Feng Hung 《International journal of molecular sciences》2021,22(1)
Endoplasmic reticulum (ER) stress response is an adaptive program to cope with cellular stress that disturbs the function and homeostasis of ER, which commonly occurs during cancer progression to late stage. Late-stage cancers, mostly requiring chemotherapy, often develop treatment resistance. Chemoresistance has been linked to ER stress response; however, most of the evidence has come from studies that correlate the expression of stress markers with poor prognosis or demonstrate proapoptosis by the knockdown of stress-responsive genes. Since ER stress in cancers usually persists and is essentially not induced by genetic manipulations, we used low doses of ER stress inducers at levels that allowed cell adaptation to occur in order to investigate the effect of stress response on chemoresistance. We found that prolonged tolerable ER stress promotes mesenchymal–epithelial transition, slows cell-cycle progression, and delays the S-phase exit. Consequently, cisplatin-induced apoptosis was significantly decreased in stress-adapted cells, implying their acquisition of cisplatin resistance. Molecularly, we found that proliferating cell nuclear antigen (PCNA) ubiquitination and the expression of polymerase η, the main polymerase responsible for translesion synthesis across cisplatin-DNA damage, were up-regulated in ER stress-adaptive cells, and their enhanced cisplatin resistance was abrogated by the knockout of polymerase η. We also found that a fraction of p53 in stress-adapted cells was translocated to the nucleus, and that these cells exhibited a significant decline in the level of cisplatin-DNA damage. Consistently, we showed that the nuclear p53 coincided with strong positivity of glucose-related protein 78 (GRP78) on immunostaining of clinical biopsies, and the cisplatin-based chemotherapy was less effective for patients with high levels of ER stress. Taken together, this study uncovers that adaptation to ER stress enhances DNA repair and damage tolerance, with which stressed cells gain resistance to chemotherapeutics. 相似文献
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Chuntao Lan Haiyang Zou Longfei Wang Meng Zhang Shuang Pan Ying Ma Yiping Qiu Zhong Lin Wang Zhiqun Lin 《Advanced materials (Deerfield Beach, Fla.)》2020,32(47):2005481
Despite recent rapid advances in metal halide perovskites for use in optoelectronics, the fundamental understanding of the electrical-poling-induced ion migration, accounting for many unusual attributes and thus performance in perovskite-based devices, remain comparatively elusive. Herein, the electrical-poling-promoted polarization potential is reported for rendering hybrid organic–inorganic perovskite photodetectors with high photocurrent and fast response time, displaying a tenfold enhancement in the photocurrent and a twofold decrease in the response time after an external electric field poling. First, a robust meniscus-assisted solution-printing strategy is employed to facilitate the oriented perovskite crystals over a large area. Subsequently, the electrical poling invokes the ion migration within perovskite crystals, thus inducing a polarization potential, as substantiated by the surface potential change assessed by Kelvin probe force microscopy. Such electrical-poling-induced polarization potential is responsible for the markedly enhanced photocurrent and largely shortened response time. This work presents new insights into the electrical-poling-triggered ion migration and, in turn, polarization potential as well as into the implication of the latter for optoelectronic devices with greater performance. As such, the utilization of ion-migration-produced polarization potential may represent an important endeavor toward a wide range of high-performance perovskite-based photodetectors, solar cells, transistors, scintillators, etc. 相似文献
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目的:探索炎性疾病患者的乳酸林格氏液(Ringer's lactate,RL)液体动力学特征以及炎性生物标记物是否可以作为协变量影响RL分布和排泄。方法:本研究为前瞻性队列研究。选择40例美国麻醉医师分级(ASA)I-II级,腹腔镜下择期胆囊切除术(胆囊炎组,n=20)或者腹腔镜下急诊阑尾切除术(阑尾炎组,n=20)。所有患者麻醉诱导前开始输注RL,按15 mL/kg,35 min内输毕。采用酶联免疫(enzyme-linked immunosorbent assay,ELISA)方法测定血浆炎症(TNF-α,IL-10和CRP)或者内皮损伤生物标记物(syndecan-1,SDC-1);利用血红蛋白(Hb)稀释-时间曲线和尿量,使用Phoenix软件,采用非线性混合效应模型分析计算RL液体动力学参数和协变量的影响。结果:与胆囊炎组相比,阑尾炎组RL从组织间隙到血浆的转运速率常数(k21)显著降低(14×10-3min-1 versus 35×10-3min-1;P=0.012)。阑尾炎组C反应蛋白(CRP)升高[中位数38.1(1.8-143.6) μg/mL versus 1.3(0.1-159.0) μg/mL;P<0.001];与清醒状态相比,麻醉期间(输液开始后30~45 min),液体从中央室中到外周室的转运速率常数(k12)显著增加(57×10-3min-1 versus 32×10-3min-1;P<0.01)。清除速率常数(k10)降低90%(0.6×10-3min-1 versus 5.3×10-3min-1;P<0.001)。无论在清醒状态还是麻醉状态下低血压均能降低液体清除;炎症或者内膜损伤的生物标记物不能作为显著影响RL液体动力学参数的协变量。结论:阑尾炎或者胆囊炎患者术前输入液体后“炎症反应的生物标记物”不是RL的液体动力学的协变量,但是两组患者中,全身麻醉期间输入液体的清除率下降。 相似文献
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A first‐principles‐based effective Hamiltonian is developed and employed to investigate finite‐temperature structural properties of a prototype of perovskite halides, that is CsPbI3. Such simulations, when using first‐principles‐extracted coefficients, successfully reproduce the existence of an orthorhombic Pnma state and its iodine octahedral tilting angles around room temperature. However, they also yield a direct transformation from Pnma to cubic upon heating, unlike measurements that reported the occurrence of an intermediate long‐range‐tilted tetragonal P4/mbm phase in‐between the orthorhombic and cubic phases. Such disagreement, which may cast some doubts about the extent to which first‐principle methods can be trusted to mimic hybrid perovskites, can be resolved by “only” changing one short‐range tilting parameter in the whole set of effective Hamiltonian coefficients. In such a case, some reasonable values of this specific parameter result in the predictions that i) the intermediate P4/mbm state originates from fluctuations over many different tilted states; and ii) the cubic phase is highly locally distorted and develops strong transverse antiphase correlation between first‐nearest neighbor iodine octahedral tiltings, before undergoing a phase transition to P4/mbm under cooling. 相似文献
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