Adaptation to Endoplasmic Reticulum Stress Enhances Resistance of Oral Cancer Cells to Cisplatin by Up-Regulating Polymerase η and Increasing DNA Repair Efficiency

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.     

基于声发射原理的矿井掘进机故障诊断技术研究

针对在我国各大矿区广泛应用的EBZ160悬臂式掘进机,基于声发射原理及技术,设计一套掘进机故障诊断声发射检测系统,获得各种故障的声发射数据样本,同时借助小波神经网络的迭代收敛性质,对故障数据样本的精确度进行验证,正确率较高,能够较好地应用于井下掘进机的故障诊断.     

Fire safe,sustainable loose furnishing

The aim of this exploratory study has been to investigate the fire properties and environmental aspects of different upholstery material combinations, mainly for domestic applications. An analysis of the sustainability and circularity of selected textiles, along with lifecycle assessment, is used to qualitatively evaluate materials from an environmental perspective. The cone calorimeter was the primary tool used to screen 20 different material combinations from a fire performance perspective. It was found that textile covers of conventional fibres such as wool, cotton and polyester, can be improved by blending them with fire resistant speciality fibres. A new three‐dimensional web structure has been examined as an alternative padding material, showing preliminary promising fire properties with regard to ignition time, heat release rates and smoke production.     

Nanocrystallization and optical properties of CsPbBr3−xIx perovskites in chalcogenide glasses

The confinement of CsPbX₃ (X = Cl, Br, and I) perovskite nanocrystals (NCs) in a stabilized inorganic glass matrix is a new strategy for improving their long-term stability and promoting their applications in the optoelectronic field. Here, in situ nanocrystallization strategy is developed to precipitate CsPbBr_3?xI_x NCs with arbitrary I/Br ratio among an elaborately designed GeS₂–Sb₂S₃-based chalcogenide glass matrix. Spherical CsPbBr_3?xI_x NCs are homogeneously distributed in the glass matrix after thermal treatment. The photoluminescence (PL) spectra show that the emission peaks of CsPbBr_3?xI_x NCs can be tuned from 570 nm to 722 nm with the replacement of Br by I. The fs transient absorption (TA) spectra reveal that there exists some structural defects in the NCs, leading to short PL decay life. This work would shed light on confining CsPbX₃ NCs into glassy matrices, facilitating their future applications in photoelectronic fields.     

4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene,a Major Active Metabolite of Bisphenol A,Triggers Pancreatic β-Cell Death via a JNK/AMPKα Activation-Regulated Endoplasmic Reticulum Stress-Mediated Apoptotic Pathway

4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), a major active metabolite of bisphenol A (BPA), is generated in the mammalian liver. Some studies have suggested that MBP exerts greater toxicity than BPA. However, the mechanism underlying MBP-induced pancreatic β-cell cytotoxicity remains largely unclear. This study demonstrated the cytotoxicity of MBP in pancreatic β-cells and elucidated the cellular mechanism involved in MBP-induced β-cell death. Our results showed that MBP exposure significantly reduced cell viability, caused insulin secretion dysfunction, and induced apoptotic events including increased caspase-3 activity and the expression of active forms of caspase-3/-7/-9 and PARP protein. In addition, MBP triggered endoplasmic reticulum (ER) stress, as indicated by the upregulation of GRP 78, CHOP, and cleaved caspase-12 proteins. Pretreatment with 4-phenylbutyric acid (4-PBA; a pharmacological inhibitor of ER stress) markedly reversed MBP-induced ER stress and apoptosis-related signals. Furthermore, exposure to MBP significantly induced the protein phosphorylation of JNK and AMP-activated protein kinase (AMPK)α. Pretreatment of β-cells with pharmacological inhibitors for JNK (SP600125) and AMPK (compound C), respectively, effectively abrogated the MBP-induced apoptosis-related signals. Both JNK and AMPK inhibitors also suppressed the MBP-induced activation of JNK and AMPKα and of each other. In conclusion, these findings suggest that MBP exposure exerts cytotoxicity on β-cells via the interdependent activation of JNK and AMPKα, which regulates the downstream apoptotic signaling pathway.     

Enhanced electromagnetic microwave absorption of Fe/C/SiCN composite ceramics targeting in integrated structure and function

The Fe/C/SiCN composite ceramics were synthesized by polymer-derived method to obtain the integration of structure and functions. The electromagnetic waves (EMW) absorption properties at X and Ku bands were investigated. The addition of nano-sized Fe particles improved the magnetic loss and impedance matching, and the carbon nanotubes generated by the iron in-situ catalysis increased the internal relaxation polarization and interfacial polarization, which together improved the EMW absorption properties significantly. In particular, the Fe/C/SiCN-9 showed the optimum reflection loss (RL) of ?31.06 dB at 10.03 GHz with an effective absorption bandwidth (EAB, RL < ?10 dB) of 3.03 GHz at 2.51 mm, indicating the excellent EMW absorption properties of Fe/C/SiCN composite ceramics.