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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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随着计算机技术以及并行求解技术的发展,区域分解方法越来越多地应用于计算电磁学的各个领域.针对微波管中的永磁聚焦系统仿真,该文提出一种基于有限元的非重叠区域分解方法,其引入一种新型传输条件,并采用内罚的方式推导出有限元弱形式.该区域分解法的最大优势是不需要引入多余的未知量,并且最终集成的有限元矩阵满足对称正定性,适合采用预处理共轭梯度法进行矩阵方程的求解.该文仿真了多个微波管永磁聚焦系统,并与商业软件Maxwell进行了详细的对比,结果表明所提出的区域分解方法和Maxwell精度相当,却拥有着更加优越的计算性能.  相似文献   
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A novel TiO2 thin film was prepared on the ceramic hollow fiber by the sol-gel method using poly(vinylpyrrolidone) (PVP) and polyvinyl alcohol (PVA) as additives. SEM images verified the formation of TiO2 layer with various thickness using different composition of titania sols. The effect of the PVP and PVA contents on the TiO2 sol properties, the separation and the antifouling performance of the ultrafiltration membranes were investigated thoroughly. When the contents of PVP and PVA were 1.0 wt% and 0.8 wt%, respectively, the resultant membrane showed a thickness of 0.55 μm with a pure water flux of 255 L m?2 h?1. In addition, the adherent foulant bovine serum albumin was applied to evaluate the antifouling performance. During the three fouling-recovery cycles, the flux recovery ratio and the flux decay ratio maintained about 99% and 30%. The BSA flux and rejection were still 169 L m?2 h?1 and 96.9% after the cycles, indicating a superior antifouling property.  相似文献   
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The degradation behavior of implants is significantly important for bone repair. However, it is still unprocurable to spatiotemporally regulate the degradation of the implants to match bone ingrowth. In this paper, a magneto-controlled biodegradation model is established to explore the degradation behavior of magnetic scaffolds in a magnetothermal microenvironment generated by an alternating magnetic field (AMF). The results demonstrate that the scaffolds can be heated by magnetic nanoparticles (NPs) under AMF, which dramatically accelerated scaffold degradation. Especially, magnetic NPs modified by oleic acid with a better interface compatibility exhibit a greater heating efficiency to further facilitate the degradation. Furthermore, the molecular dynamics simulations reveal that the enhanced motion correlation between magnetic NPs and polymer matrix can accelerate the energy transfer. As a proof-of-concept, the feasibility of magneto-controlled degradation for implants is demonstrated, and an optimizing strategy for better heating efficiency of nanomaterials is provided, which may have great instructive significance for clinical medicine.  相似文献   
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Zhao  Kui  He  Fangmin  Meng  Jin  Wu  Hao  Zhang  Lei 《Wireless Networks》2021,27(3):1671-1681
Wireless Networks - In such mobile platforms as ships and aircraft, the detection and reconnaissance devices are near to the communication facilities. When working at the same time, they will...  相似文献   
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以驻村扶贫点滇西南L县X村的光棍为研究对象,侧重个体精准性,强调个体因果性的特征,运用小数据分析该村光棍的贫困特征和生成原因,基于马斯洛需求层次理论探索光棍内生动力激发机制.研究表明:农村光棍趋于年轻化,形势严峻;光棍成因受到外部资源匮乏的限制,又受到自身资源缺陷的制约,内外因相互影响,但外因只有通过内因才能发挥作用.探讨通过需求原理激发光棍群体的内生动力,构建长效治理机制,让光棍群体最大限度实现人生价值,提升社会获得感和幸福感.  相似文献   
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