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.     

As the number falls,alternatives to the Hagberg–Perten falling number method: A review

This review examines the application, limitations, and potential alternatives to the Hagberg–Perten falling number (FN) method used in the global wheat industry for detecting the risk of poor end-product quality mainly due to starch degradation by the enzyme α-amylase. By viscometry, the FN test indirectly detects the presence of α-amylase, the primary enzyme that digests starch. Elevated α-amylase results in low FN and damages wheat product quality resulting in cakes that fall, and sticky bread and noodles. Low FN can occur from preharvest sprouting (PHS) and late maturity α-amylase (LMA). Moist or rainy conditions before harvest cause PHS on the mother plant. Continuously cool or fluctuating temperatures during the grain filling stage cause LMA. Due to the expression of additional hydrolytic enzymes, PHS has a stronger negative impact than LMA. Wheat grain with low FN/high α-amylase results in serious losses for farmers, traders, millers, and bakers worldwide. Although blending of low FN grain with sound wheat may be used as a means of moving affected grain through the marketplace, care must be taken to avoid grain lots from falling below contract-specified FN. A large amount of sound wheat can be ruined if mixed with a small amount of sprouted wheat. The FN method is widely employed to detect α-amylase after harvest. However, it has several limitations, including sampling variability, high cost, labor intensiveness, the destructive nature of the test, and an inability to differentiate between LMA and PHS. Faster, cheaper, and more accurate alternatives could improve breeding for resistance to PHS and LMA and could preserve the value of wheat grain by avoiding inadvertent mixing of high- and low-FN grain by enabling testing at more stages of the value stream including at harvest, delivery, transport, storage, and milling. Alternatives to the FN method explored here include the Rapid Visco Analyzer, enzyme assays, immunoassays, near-infrared spectroscopy, and hyperspectral imaging.     

提升我国电磁安全能力的战略思考

阐述电磁安全的战略背景,分析电磁兼容到电磁安全的演化过程,剖析"自扰、互扰、敌扰"等现实迫切问题,阐明电磁干扰、电磁兼容等基本概念和相互关系,提出新需求、新技术、新趋势引发电磁兼容与电磁安全的"六大技术挑战",指出只有在认识和思维上系统性地实现"三个转变",才能实现电磁安全整体能力的提升,最后提出"电磁强国"的"五维布局"建议.     

一种新型的室温快速固化胶黏剂的研制

本文开发了一种新型的方舱夹芯板用室温固化高强度环氧结构胶黏剂,验证了其物化特性、相关力学性能和环境适应性。结果表明此胶黏剂具有优良性能,可以满足方舱用大板胶黏剂的使用需求。     

CaDHN3, a Pepper (Capsicum annuum L.) Dehydrin Gene Enhances the Tolerance against Salt and Drought Stresses by Reducing ROS Accumulation

Dehydrins (DHNs) play an important role in abiotic stress tolerance in a large number of plants, but very little is known about the function of DHNs in pepper plants. Here, we isolated a Y₁SK₂-type DHN gene “CaDHN3” from pepper. To authenticate the function of CaDHN3 in salt and drought stresses, it was overexpressed in Arabidopsis and silenced in pepper through virus-induced gene silencing (VIGS). Sub-cellular localization showed that CaDHN3 was located in the nucleus and cell membrane. It was found that CaDHN3-overexpressed (OE) in Arabidopsis plants showed salt and drought tolerance phenotypic characteristics, i.e., increased the initial rooting length and germination rate, enhanced chlorophyll content, lowered the relative electrolyte leakage (REL) and malondialdehyde (MDA) content than the wild-type (WT) plants. Moreover, a substantial increase in the activities of antioxidant enzymes; including the superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX), and lower hydrogen peroxide (H₂O₂) contents and higher O₂^•− contents in the transgenic Arabidopsis plants. Silencing of CaDHN3 in pepper decreased the salt- and drought-stress tolerance, through a higher REL and MDA content, and there was more accumulation of reactive oxygen species (ROS) in the CaDHN3-silenced pepper plants than the control plants. Based on the yeast two-hybrid (Y2H) screening and Bimolecular Fluorescence Complementation (BiFC) results, we found that CaDHN3 interacts with CaHIRD11 protein in the plasma membrane. Correspondingly, the expressions of four osmotic-related genes were significantly up-regulated in the CaDHN3-overexpressed lines. In brief, our results manifested that CaDHN3 may play an important role in regulating the relative osmotic stress responses in plants through the ROS signaling pathway. The results of this study will provide a basis for further analyses of the function of DHN genes in pepper.     

Blends of Bio-Based Poly(Limonene Carbonate) with Commodity Polymers

In this study, blends of the bio-based poly(limonene carbonate) (PLimC) with different commodity polymers are investigated in order to explore the potential of PLimC toward generating more sustainable polymer materials by reducing the amount of petro- or food-based polymers. PLimC is employed as minority component in the blends. Next to the morphology and thermal properties of the blends the impact of PLimC on the mechanical properties of the matrix polymers is studied. The interplay of incompatibility and zero-shear melt viscosity contrast determines the blend morphology, leading for all blends to a dispersed droplet morphology for PLimC. Blends with polymers of similar structure to PLimC (i.e., aliphatic/aromatic polyester) show the best performance with respect to mechanical properties, whereas blends with polystyrene or poly(methyl methacrylate) are too brittle and polyamide 12 blends show very low elongations at break. In blends with Ecoflex (poly(butylene adipate-co-terephthalate)) and Arnitel EM400 (copoly(ether ester)) with poly(butylene terephthalate) hard and polytetrahydrofuran soft segments) a threefold increase in E-modulus can be achieved, while keeping the elongation at break at reasonable high values of ≈200%, making these blends highly interesting for applications.     

Understanding grain refining and anti Si-poisoning effect in Al-10Si/Al-5Nb-B system

Grain refinement is critical for fabricating high-quality Al-Si casting components in the application of automobile and aerospace industries,while the well-known Si-poisoning effect makes it difficult.Nbbased refiners offer an effective method to refine Al-Si casting alloys,but their anti Si-poisoning capability is far from being understood.In this work,the grain refining mechanism and the anti Si-poisoning effect in the Al-10 Si/Al-5 Nb-B system were systematically investigated by combining transmission electron microscope,first-principles calculations,and thermodynamic calculations.It is revealed that NbB₂provides the main nucleation site in the Al-10 Si ingot inoculated by 0.1 wt.%Nb Al-5 Nb-B refiner.The exposed Nb atoms on the(0001)NbB₂and(1-100)NbB₂surface can be substituted by Al to form(Al,Nb)B₂intermedia layers.In addition,a layer of NbAl₃-like compound(NbAl₃')can cover the surface of NbB₂with the orientation relation of(1-100)[11-20]NbB_2//(110)[110]NbAl₃'.Both of the(Al,Nb)B₂and NbAl₃'intermedia layers contribute to enhancing the nucleation potency of NbB₂particles.These discoveries provide fundamental insight to the grain refining mechanism of the Nb-B based refiners for Al-Si casting alloys and are expected to guide the future development of stronger refiners for Al-Si casting alloys.     

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.     

Theoretical study on a kind of cyclization mechanism of boron trichloride and hexamethyldisilazane to form the borazine ring for SiBCN ceramics precursor

Borazine rings act as a pivotal part in siliconboroncarbonitride ceramics (SiBCN) for high-temperature stability and great resistance to crystallization. A detailed investigation of the ring formation mechanism will guide the design and synthesis of SiBCN to meet application requirements under extreme conditions. Boron trichloride (BCl₃) and hexamethyldisilazane (HN(SiMe₃)₂) are common raw materials for the synthesis of precursors for SiBCN. In this paper, quantum chemical calculation was used to study the cyclization reaction mechanism between BCl₃ and HN(SiMe₃)₂ to form trichloroborazine (TCBZ) at the MP2/6-31G (d,p) level of theory. We discussed the structure properties, reaction pathways, energy barriers, reaction rates, and other aspects in detail. The results show that BCl₃ and HN(SiMe₃)₂ alternately participate in the reaction process, accompanied by the release of trimethylchlorosilane (TMCS), and that the entire reaction shows an absolute advantage in terms of energy. In the Step by step reaction, lower reaction barriers are formed due to the introduction of BCl₃ with more heat released compared to that for the introduction of HN(SiMe₃)₂. The final single-molecule cyclization and TMCS elimination steps are found to be faster compared to all previous bimolecular reactions.     

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.