Cytosolic escape of mitochondrial DNA triggers cGAS-STING-NLRP3 axis-dependent nucleus pulposus cell pyroptosis

Low back pain (LBP) is a major musculoskeletal disorder and the socioeconomic problem with a high prevalence that mainly involves intervertebral disc (IVD) degeneration, characterized by progressive nucleus pulposus (NP) cell death and the development of an inflammatory microenvironment in NP tissue. Excessively accumulated cytosolic DNA acts as a damage-associated molecular pattern (DAMP) that is monitored by the cGAS-STING axis to trigger the immune response in many degenerative diseases. NLRP3 inflammasome-dependent pyroptosis is a type of inflammatory programmed death that promotes a chronic inflammatory response and tissue degeneration. However, the relationship between the cGAS-STING axis and NLRP3 inflammasome-induced pyroptosis in the pathogenesis of IVD degeneration remains unclear. Here, we used magnetic resonance imaging (MRI) and histopathology to demonstrate that cGAS, STING, and NLRP3 are associated with the degree of IVD degeneration. Oxidative stress induced cGAS-STING axis activation and NLRP3 inflammasome-mediated pyroptosis in a STING-dependent manner in human NP cells. Interestingly, the canonical morphological and functional characteristics of mitochondrial permeability transition pore (mPTP) opening with the cytosolic escape of mitochondrial DNA (mtDNA) were observed in human NP cells under oxidative stress. Furthermore, the administration of a specific pharmacological inhibitor of mPTP and self-mtDNA cytosolic leakage effectively reduced NLRP3 inflammasome-mediated pyroptotic NP cell death and microenvironmental inflammation in vitro and degenerative progression in a rat disc needle puncture model. Collectively, these data highlight the critical roles of the cGAS-STING-NLRP3 axis and pyroptosis in the progression of IVD degeneration and provide promising therapeutic approaches for discogenic LBP.Subject terms: Cell death, Diseases     

一类随机环境中的随机游动

研究了在环境平稳遍历时,右半直线上可逗留的随机环境中的随机游动的常返性和非常返性,给出非常返、正常返、零常返的充要条件,并讨论了极限性质.作为推论,给出P独立同分布时的相应结论.     

基于表面增强拉曼光谱技术的心肌生物标志物检测

心血管疾病(CVD)是全球最主要的死亡原因,急性心肌梗死(AMI)是心血管疾病致死的主要病因,安全快速地诊断AMI对于降低患者的死亡率至关重要。因常用的检测方法如心电图(ECG)缺乏足够的敏感性,寻找并针对AMI生物标志物开展高灵敏检测已成为早期检测AMI重要手段。心肌肌钙蛋白I(cTnI)、肌酸激酶同工酶(CK-MB)和肌红蛋白(Myo)是目前公认的检测AMI的重要心肌生物标志物。在过去的几十年里,许多生物传感器被开发出来用于检测心肌生物标志物,其中基于表面增强拉曼光谱(SERS)的心肌生物标志物检测技术迅速发展,并表现出独特的技术优势和广阔的应用前景。本文首先介绍了多种心肌生物标志物及其与AMI的关联,在此基础上概述主要的心肌生物标志物检测方法的原理、优势及局限性,重点介绍近年来新兴的SERS技术及其在心肌生物标志物传感方面的最新研究进展,并对该技术在AMI诊断方面的应用前景以及有待突破的瓶颈进行了讨论和展望。     

石墨基液流电池复合双极板

液流电池是一种安全性高、使用寿命长、可扩展的大规模储能系统,可以协助电网调峰储能,提高能源利用率,发展前景广阔。双极板是液流电池的重要组成部分。功能上起到了分隔、串联电池、传导电流、为电堆提供结构支撑等作用。从成本构成角度看,双极板的价格占电堆成本的比重也较大。开发高性能、低成本的双极板对加快液流电池的商业化应用具有重要意义,也是目前业界的迫切需求。虽然文献上报道了许多针对液流电池双极板开发的工作,但是目前高性能、低成本的液流电池双极板产品仍无法充分满足市场需求。本文着重介绍了石墨基复合双极板的研究现状,介绍了材料选择、工艺流程对关键性能的影响,对相关工作进行了评述,并为液流电池双极板的开发提出了建议。     

噻唑类杀菌剂的合成及生物活性研究进展

噻唑类化合物具有较好的抗真菌,抗细菌及抗微生物活性,在新农药和医药中得到广泛地应用。简要介绍了国内外近年来噻唑类杀菌剂的合成及生物活性研究进展。参考文献38篇。     

The role of cooling rate in crystallization-driven block copolymer self-assembly

Self-assembly of crystalline-coil block copolymers (BCPs) in selective solvents is often carried out by heating the mixture until the sample appears to dissolve and then allowing the solution to cool back to room temperature. In self-seeding experiments, some crystallites persist during sample annealing and nucleate the growth of core-crystalline micelles upon cooling. There is evidence in the literature that the nature of the self-assembled structures formed is independent of the annealing time at a particular temperature. There are, however, no systematic studies of how the rate of cooling affects self-assembly. We examine three systems based upon poly(ferrocenyldimethylsilane) BCPs that generated uniform micelles under typical conditions where cooling took pace on the 1–2 h time scale. For example, several of the systems generated elongated 1D micelles of uniform length under these slow cooling conditions. When subjected to rapid cooling (on the time scale of a few minutes or faster), branched structures were obtained. Variation of the cooling rate led to a variation in the size and degree of branching of some of the structures examined. These changes can be explained in terms of the high degree of supersaturation that occurs when unimer solutions at high temperature are suddenly cooled. Enhanced nucleation, seed aggregation, and selective growth of the species of lowest solubility contribute to branching. Cooling rate becomes another tool for manipulating crystallization-driven self-assembly and controlling micelle morphologies.

In the self-assembly of crystalline-coil block copolymers in solution, heating followed by different cooling rates can lead to different structures.     

低偏振相关损耗全息光栅波分复用器的设计

对基于掺杂铌酸锂材料的体光栅波分复用器主要结构和光栅记录参量提出了一种优化设计方法.采用严格耦合波理论,对两种偏振不同入射角和不同记录晶体厚度下的器件关键性能参量,如插入损耗和偏振相关损耗等进行了优化.数值结果证明采用优化设计的晶体厚度和光栅记录时的入射角,在获得相当低的偏振相关损耗的同时,也能够获得较低的插入损耗,实现了综合性能优化的波分复用器设计.实验结果证明用优化设计的参量能有效降低波分复用器件的插入损耗和偏振相关损耗.     

提升小波变换与分形相结合的图像压缩

提出了一种提升小波变换与分形相结合的图像压缩方案.充分利用小波变换后系数能量的分布特性,对提升小波变换后的低频部分采用改进的分形图像压缩编码,其余部分采用集合分裂嵌入块(SPECK)编码算法.试验结果表明,该方法在提高了压缩效率的同时,获得了较高的恢复图像质量.     

光纤环形镜线形腔掺Er3+光纤激光器输出特性的数值分析

在分析光纤环形镜工作原理的基础上,给出了基于光纤环形镜的线形腔掺Er3+光纤激光器相位和幅度的振荡条件.通过求解速率方程,理论分析了其输出特性,获得了稳态条件下激光器输出功率、阈值泵浦功率和斜率效率的解析表达式.推导出激光器工作所需掺Er3+光纤最短长度,并在给定泵浦光功率时,在特定输出波长上获得最大输出功率所需最佳掺Er3+光纤长度的表达式,且通过实验进行了验证.     

多光束在分形粗糙表面散射的仿真

采用矩量法(MOM),分析了多光束在分形粗糙导体表面的散射分布.对在不同入射角、光束宽度控制因子、光束照射区宽度、表面均方根高度和表面分维数情况下的散射进行了数值仿真.仿真结果表明了各参量的变化对散射分布的影响.根据仿真计算结果给出了最佳的散射测量区域,为减少多光束测量的误差提供了一定的参考.