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.     

基于有限元的区域分解方法在永磁聚焦系统仿真中的应用

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.     

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.     

基于蜻蜓翅脉结构的连续碳纤维增强树脂基复合材料仿生设计与增材制造

以具有轻质高强优异性能的蜻蜓翅脉结构为设计灵感，在分析翅脉网格结构抗冲击原理的基础上，设计了传统和仿生两类对比结构。采用熔融挤出3D打印机成功制备了具有不同结构的连续碳纤维增强聚乳酸复合材料试样，并对不同结构复合材料试样的拉伸性能和抗冲击性能进行了测试和对比分析。研究分析结果表明：由于拉伸力方向上的连续碳纤维含量相对较少，限制了仿生结构复合材料抗拉强度的提高，但仿生结构的平均抗拉强度为传统结构的1.18倍；当仿生结构复合材料试样受到冲击力时，其内部六边形结构的连接角度会发生变化，从而极大消耗冲击能量，同时具有六边形网格结构的连续碳纤维可以有效阻碍裂纹的扩展，因此仿生结构的平均冲击韧性可以达到传统结构的2.46倍；仿生蜻蜓翅脉结构可以显著提高增材制造复合材料的综合力学性能，且对于抗冲击性能的提高具体突出效果。连续碳纤维增强树脂基复合材料的有效可行的仿生蜻蜓翅脉结构设计和增材制造，可极大扩展其在高冲击载荷领域中的相应应用。     

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.     

基于PBFT区块链技术的电网企业仓储系统

提出了一种基于实用拜占庭容错(PBFT)算法的区块链技术,首先对传统的实用拜占庭容错算法原理进行了阐述,该传统算法包含前期、需求、预准备、准备、确认、答复6个阶段,但传统算法具有实时性差、缺乏惩罚机制、带宽高的缺点。针对出现的这些问题,又对传统算法进行了改进,具体涉及记账节点、共识过程以及视图切换过程。通过测试进一步证明了该改进算法的实用性,并将该算法应用于电网企业中,构建的虚拟仓库实现了联储联备,降低了库存资金的耗费,并且提高了电网企业库存管理的效率。