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
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
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
Coal mining can dramatically change hydrogeological conditions and induce serious environmental problems. Fifty groundwater samples were collected from the main aquifers in the Yuaner coal mine (Anhui Province, China). The results show that the main hydrogeochemical processes in the mine include dissolution, precipitation, pyrite oxidation, desulfurization, and cation exchange. The Neogene porous aquifer is affected by groundwater flow conditions; its main hydrogeochemical processes are dissolution of carbonate minerals and gypsum, and cation exchange. The Permian coal measure’s fractured sandstone aquifer was confirmed to be controlled by the region’s geological structure; its main hydrogeochemical processes are desulfurization and cation exchange. The Carboniferous Taiyuan limestone aquifer was determined by both groundwater flow conditions and regional geological structure; its main hydrogeochemical processes are dissolution of carbonate minerals and gypsum, pyrite oxidation, and cation exchange. Additionally, hydrogeochemical inverse modeling of the groundwater flow path confirm the hydrochemistry results and principal component analysis.
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
Porous g-C3N4 nanosheets (PCN) were prepared by the nickel-assisted one-step thermal polymerization method.Hydrogen (H2) which was produced by the reaction between nickel (Ni) foam and ammonia (NH3) defined the structure and properties of PCN.During the formation of PCN,the participation of H2 not only enhanced the spacing between layers but also boosted the specific surface area that more active sites were exposed.Additionally,H2 promoted pores formation in the nanosheets,which was beneficial to the transfer of photons through lamellar structure and improved the absorption efficiency of visible light.Remarkably,the obtained PCN possessed better Cr(Ⅵ) photocatalytic reduction efficiency than pure g-C3N4.The reaction rate constant (k) of PCN (0.013 min-1) was approximately twice that of bare g-C3N4 (0.007 min-1).Furthermore,the effects of original pH and concentration of Cr(Ⅵ)-containing solution on removal efficiency of Cr(Ⅵ) were explored.A possible photocatalytic mechanism was proposed based on the experiments of radical scavengers and photoelectrochemical characterizations. 相似文献