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.     

A Biologically Muscle-Inspired Polyurethane with Super-Tough,Thermal Reparable and Self-Healing Capabilities for Stretchable Electronics

Polymeric elastomers play an increasingly important role in the development of stretchable electronics. A highly demanded elastic matrix is preferred to own not only excellent mechanical properties, but also additional features like high toughness and fast self-healing. Here, a polyurethane (DA-PU) is synthesized with donor and acceptor groups alternately distributed along the main chain to achieve both intra-chain and inter-chain donor-acceptor self-assembly, which endow the polyurethane with toughness, self-healing, and, more interestingly, thermal repair, like human muscle. In detail, DA-PU exhibits an amazing mechanical performance with elongation at break of 1900% and toughness of 175.9 MJ m⁻³. Moreover, it shows remarkable anti-fatigue and anti-stress relaxation properties as manifested by cyclic tensile and stress relaxation tests, respectively. Even in case of large strain deformation or long-time stretch, it can almost completely restore to original length by thermal repair at 60 °C in 60 s. The self-healing speed of DA-PU is gradually enhanced with the increasing temperature, and can be 1.0–6.15 µm min⁻¹ from 60 to 80 °C. At last, a stretchable and self-healable capacitive sensor is constructed and evaluated to prove that DA-PU matrix can ensure the stability of electronics even after critical deformation and cut off.     

Interleukin-1β Modulation of the Mechanobiology of Primary Human Pulmonary Fibroblasts: Potential Implications in Lung Repair

Pro-inflammatory cytokines like interleukin-1β (IL-1β) are upregulated during early responses to tissue damage and are expected to transiently compromise the mechanical microenvironment. Fibroblasts are key regulators of tissue mechanics in the lungs and other organs. However, the effects of IL-1β on fibroblast mechanics and functions remain unclear. Here we treated human pulmonary fibroblasts from control donors with IL-1β and used Atomic Force Microscopy to unveil that IL-1β significantly reduces the stiffness of fibroblasts concomitantly with a downregulation of filamentous actin (F-actin) and alpha-smooth muscle (α-SMA). Likewise, COL1A1 mRNA was reduced, whereas that of collagenases MMP1 and MMP2 were upregulated, favoring a reduction of type-I collagen. These mechanobiology changes were functionally associated with reduced proliferation and enhanced migration upon IL-1β stimulation, which could facilitate lung repair by drawing fibroblasts to sites of tissue damage. Our observations reveal that IL-1β may reduce local tissue rigidity by acting both intracellularly and extracellularly through the downregulation of fibroblast contractility and type I collagen deposition, respectively. These IL-1β-dependent mechanical effects may enhance lung repair further by locally increasing pulmonary tissue compliance to preserve normal lung distension and function. Moreover, our results support that IL-1β provides innate anti-fibrotic protection that may be relevant during the early stages of lung repair.     

基于.NET技术的高校后勤报修系统设计与实现

随着高校办学规模的不断扩大,原基于师生服务中心的现场人工报修方式,已无法满足日益增长的后勤报修维修的需求。根据学校的实际情况,对学校后勤管理系统进行分析,得出高职院后勤管理系统应满足在线报修、在线查看、维修反馈、在线评价等功能的需求;同时对高校后勤报修系统进行系统架构设计、网络架构设计、UML类图设计、数据库设计等。通过C#完成系统的编写,最终实现后勤报修系统的开发。     

丙烯酸装置循环气压缩机叶片损伤分析与修复

某石化公司丙烯酸装置循环气压缩机在运行过程中,一级叶片突然发生断裂,导致机组停机。采用宏观检查、扫描电子显微镜、能谱分析等方法对断裂叶片进行检验和检测,将断裂叶片的材质、裂纹及断口特征检测结果与疲劳断裂特征和机组运行状况进行对比,确定压缩机叶片的断裂系其达到疲劳寿命所致,提出采用激光熔覆方法对压缩机叶片进行修复,介绍了修复工艺操作程序要点,可为同类故事的处理提供参考。     

埋地金属管道高压连续复合软管内衬修复技术研究与现场应用

针对服役时间长、长距离穿越季节性水域的埋地金属管道修复施工难题,开展了高压连续复合软管内衬修复技术研究与试验应用。高压连续复合软管由内衬层、增强层、保护层三部分组成,管道中间断管处接头连接方式为包裹连接,端部的连接方式为法兰碰头连接。结果表明:DN100/PN6.0管材平均爆破强度11.8 MPa,轴向拉伸强度192 kN,维卡软化温度77.3℃;建立的工艺计算方法可用于配套设备选型和施工长度设计,理论计算轴向拉伸强度192 kN,理论最大直线施工长度5.0 km,现场应用最大施工长度1.9 km;施工流程中管道清洗、焊瘤检测、扭矩释放是施工作业流程的关键控制点。该技术可提高施工时效50%,节省工程费用20%~30%。     

Investigation on the effectiveness of the repair method 8.3 “Corrosion protection by increasing the electrical resistivity” in chloride-containing concrete Part 2: Chloride redistribution in concrete after application of a system sealing surface protective coating

This DFG-funded research project aimed to gain a better understanding of the mechanisms of the W-Cl repair principle within the framework of fundamental investigations, to contribute to the creation of the necessary basis for a broader application of the repair principle in practice. The focus was on the development of a model to describe the chloride redistribution after the application of a system sealing surface protective coating. On the basis of Fick's second law of diffusion, a mathematical model with a self-contained analytical solution was developed, with the help of which the chloride redistribution after application of a system sealing surface protective coating can be calculated under the idealized assumption of complete water saturation of the concrete. Furthermore, the influence of the dehydration of the concrete, expected as a result of the application of the repair principle W-Cl, on the chloride redistribution was investigated. On the basis of laboratory tests and numerical simulations, material-specific reduction functions were developed to quantify the relationship between the chloride diffusion coefficient and the ambient humidity.     

基于趋势分析的舰载机预防性维修工作优化技术研究

针对缩减舰上保障规模和提高舰载机的完好率的需求，提出舰载机预防性维修工作优化方法。分析了如何选取优化项目和参数，对比分析了各种趋势分析方法的适用性，采用基于飞参数据的趋势分析方法，刻画系统或部件的性能变化趋势，提供适合单机的舰载机预防性维修工作优化决策支撑，并以典型系统进行了案例应用，形成了一种新的舰载机提高保障效能、提升系统安全性水平的技术途径。