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.     

浅谈紫砂“云肩如意壶”的造型美感以及文化意境

紫砂壶是中国传统茶文化的重要组成部分,是中国特有的饮茶器具,自古以来深受很多爱茶人士的喜爱。紫砂壶在宋朝开始出现,更是盛行于明清,到如今五六百年时间里,经历无数兴废衰荣之后发展逐渐成熟,更是掀起了一阵世界性的紫砂文化热潮。紫砂壶集篆刻、绘画、书法等诸多艺术于一体,造型个性美观、风格迥异、与众不同、独树一帜,令很多人为之着迷。更特别的是紫砂壶和一般的陶器不同,由于材质以及制造工艺的特殊性,更加经久耐用,并且烧成后的紫砂壶保温性和透气性都很好,能较长时间保存茶叶的色、香、味,故称其为:“世间茶具称为首”。笔者以紫砂壶“云肩如意壶”为例,浅谈它的造型特征以及文化意境。     

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.     

下扬子地区下志留统风暴沉积特征及风暴作用对泥页岩品质的影响

近年来在下扬子地区页岩气地质调查井所获取的地层岩心资料，揭示该地区下志留统风暴沉积较为发育。基于精细的岩心观察描述，详细分析了下扬子地区下志留统高家边组下段中上部风暴沉积的特征，并阐明了风暴作用对泥页岩的影响。研究表明：研究区风暴岩岩性偏细，以粉砂岩为主，石英含量较高，结构成熟度较低，具2种不同的粒度概率曲线；主要发育底部冲刷面、块状层理、平行层理、丘状交错层理、波纹交错层理、准同生变形构造等沉积构造；垂向上主要识别出4种风暴沉积序列，均具有从底到顶粒度变细的沉积特征，不同的沉积序列与风暴流能量的强弱有关。下扬子地区早志留世频繁的风暴活动与研究区的古地理背景和古气候条件具有内在联系。特大型风暴对浅海陆棚深水区的细粒泥质沉积物特征产生重要影响，包括降低有机质含量、减少单层厚度、破坏垂向连续性、改变原始沉积构造和侧向稳定性等，总体上降低了泥页岩的品质。因此，研究认为在页岩气的勘探和评价过程中应重视风暴因素对陆棚深水区原始泥质沉积物的影响。     

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.