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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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Tae-min Yeo Jung-Wook Cho Ivan Hung Zhehong Gan Sabyasachi Sen 《Journal of the American Ceramic Society》2022,105(10):6140-6148
The structure of mold flux glasses in the system CaO-(Na,Li)2O-SiO2-CaF2 with unusually high modifier contents, stabilized by the addition of ∼4 mol% B2O3, is studied using 7Li, 23Na, 19F, 11B, and 29Si magic-angle-spinning (MAS), and 7Li{19F} and 23Na{19F} rotational echo double-resonance (REDOR) nuclear magnetic resonance (NMR) spectroscopy. When taken together, the spectroscopic results indicate that the structure of these glasses consists primarily of dimeric [Si2O7]−6 units that are linked to the (Ca,Na,Li)-O coordination polyhedra, and are interspersed with chains of corner-shared BO3 units. The F atoms in the structure are exclusively bonded to Ca atoms, forming Ca(O,F)n coordination polyhedra. This structural scenario is shown to be consistent with the crystallization of cuspidine (3CaO·2SiO2·CaF2) from the parent melts on slow supercooling. The progressive addition of Li to a Na-containing base composition results in a corresponding increase in the undercooling required for the nucleation of cuspidine in the melt, which is attributed to the frustrated local structure caused by the mixing of alkali ions. 相似文献
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Wireless Personal Communications - In this paper, we investigate the effect of multipath fading on the combined signal-to-noise ratio (SNR) in conjunction with multiband orthogonal frequency... 相似文献
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为了检验选择性非催化还原(SNCR)脱硝技术在高效低NOx液态排渣煤粉工业锅炉中的应用效果,本文在一台8.4MW有机热载体锅炉炉膛内开展了SNCR脱硝技术工业化试验研究。选用尿素作为还原剂,搭建了工业化SNCR脱硝试验平台。在10%、15%、20%三种浓度尿素溶液下进行了不同尿素溶液喷射量、不同氧含量、不同锅炉负荷下的SNCR脱硝试验研究。试验结果表明,提出的“低NOx燃烧+SNCR脱硝”耦合技术方案是可行的,SNCR脱硝效率在80%以上,完全能够达到烟气中NOx低于50mg/m3的超低排放要求。 相似文献
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以超临界二氧化碳(S-CO_2)干气密封为研究对象,建立变黏度变密度雷诺方程,通过构建物性数据库的方式对黏度及密度进行处理,并采用有限差分法对控制方程进行求解,得到端面压力分布,并计算开启力、泄漏量、摩擦扭矩和气膜刚度等稳态性能参数。结果表明:随着压力、转速的增大,开启力、泄漏量、摩擦扭矩、气膜刚度等参数均增大;随着槽坝比和槽深的增加,开启力、泄漏量和气膜刚度均增大,摩擦扭矩减小;随着槽数的增加,各稳态性能参数均减小;将槽坝比控制在0.5~1的范围内,有助于提高密封稳定性。 相似文献