TRX2/Rab35 Interaction Impairs Exosome Secretion by Inducing Rab35 Degradation

Given that exosomes mediate intercellular communication by delivering cellular components to recipient cells or tissue, they have the potential to be engineered to deliver therapeutic payloads. However, the regulatory mechanism of exosome secretion is poorly understood. In addition, mitochondrial components have been found in exosomes, suggesting communication between mitochondria and exosomes. However, the molecular mechanism of the mitochondria and vesicle interaction remains unclear. Here, we showed that mitochondrial thioredoxin 2 (TRX2) decreased exosome concentrations and inhibited HCT116 cell migration. Coimmunoprecipitation/mass spectrometry (Co-IP/MS) showed that TRX2 interacted with Rab35. TRX2 and Rab35 bound to each other at their N-terminal motifs and colocalized on mitochondria. Furthermore, TRX2 induced Rab35 degradation, resulting in impaired exosome secretion. Additionally, Rab35 mediated the suppressive effects of TRX2 on cell migration, and TRX2 suppressed cell migration through exosomes. Taken together, this study first found an interaction between TRX2 and Rab35. These results revealed a new role for TRX2 in the regulation of exosome secretion and cell migration and explained the upstream regulatory mechanism of Rab35. Furthermore, these findings also provide new molecular evidence for communication between mitochondria and vesicles.     

Biomimetic Nanosponges Enable the Detoxification of Vibrio vulnificus Hemolysin

Vibrio vulnificus (V. vulnificus) infection-associated multiple antibiotic resistance has raised serious public health concerns. Recently, nanosponges (NSs) have been expected to provide innovative platforms for addressing antibacterial and drug-resistant challenges by targeting various pore-forming toxins (PFTs). In the present study, we constructed NSs to explore the effects and possible mechanism of recombinant V. vulnificus hemolysin (rVvhA)-induced injuries. In vitro, NSs significantly reversed rVvhA-induced apoptosis and necrosis, and improved toxin-induced intracellular reactive oxygen species (ROS) production, adenosine triphosphate (ATP) depletion, and apoptosis signaling pathway disruption. To explore the clinical translation potential of NSs, we established VvhA-induced septicemia and wound infection mouse models, respectively, and further found NSs could notably attenuate rVvhA-induced acute toxicity and septicemia-associated inflammation, as well as local tissue damage. In a conclusion, NSs showed excellent protective effects against rVvhA-induced toxicity, thus providing useful insights into addressing the rising threats of severe V. vulnificus infections.     

基于耦合分析的热流系统协同设计

作为综合能源系统的一部分, 热流系统通常在稳态假设下设计其物理系统, 在此基础上设计控制器. 这种 方法忽略了系统与控制器设计间的耦合关系, 导致系统暂态性能不佳. 为此, 本文提出一种协同设计方法, 以系统总 质量、熵产率以及控制效果为设计度量, 基于热流系统数学模型及其熵产率模型, 结合嵌套设计方法和同步设计方 法完成系统设计. 考虑到设计过程中设计参数多、变量范围大的问题, 引入时间序列模式距离, 构造相关度度量函 数来分析物理系统与控制器之间的耦合关系, 从而减少非耦合参数. 同时, 利用数据分析方法进一步缩小了待设计 参数范围. 为验证方法的有效性, 以一个理想热流系统为设计实例, 仿真结果表明, 通过相关度度量函数及其数据分 析, 可以将设计参数个数减少66%, 选取范围缩小26%. 相比于传统顺序设计方法, 经过协同设计方法设计的系统控 制误差可减少29%, 且设计控制器抗扰能力也优于频域方法和SIMC方法.     

Differential MicroRNA Expression in Porcine Endometrium Related to Spontaneous Embryo Loss during Early Pregnancy

Litter size is an important indicator to measure the production capacity of commercial pigs. Spontaneous embryo loss is an essential factor in determining sow litter size. In early pregnancy, spontaneous embryo loss in porcine is as high as 20–30% during embryo implantation. However, the specific molecular mechanism underlying spontaneous embryo loss at the end of embryo implantation remains unknown. Therefore, we comprehensively used small RNA sequencing technology, bioinformatics analysis, and molecular experiments to determine the microRNA (miRNA) expression profile in the healthy and arresting embryo implantation site of porcine endometrium on day of gestation (DG) 28. A total of 464 miRNAs were identified in arresting endometrium (AE) and healthy endometrium (HE), and 139 differentially expressed miRNAs (DEMs) were screened. We combined the mRNA sequencing dataset from the SRA database to predict the target genes of these miRNAs. A quantitative real-time PCR assay identified the expression levels of miRNAs and mRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on differentially expressed target genes of DEMs, mainly enriched in epithelial development and amino acids metabolism-related pathways. We performed fluorescence in situ hybridization (FISH) and the dual-luciferase report gene assay to confirm miRNA and predicted target gene binding. miR-205 may inhibit its expression by combining 3′-untranslated regions (3′ UTR) of tubulointerstitial nephritis antigen-like 1 (TINAGL1). The resulting inhibition of angiogenesis in the maternal endometrium ultimately leads to the formation of arresting embryos during the implantation period. This study provides a reference for the effect of miRNA on the successful implantation of pig embryos in early gestation.     

负载氯喹的骨靶向纳米颗粒打破肿瘤细胞增殖与骨吸收之间的恶性循环

肿瘤细胞增殖与骨吸收之间的恶性循环加剧了骨肿瘤的进展和转移风险.为此,我们设计并制备了聚乙二醇-阿仑膦酸钠修饰的聚多巴胺(PPA)纳米粒子,并在其表面负载自噬抑制剂氯喹(CQ),期望利用该治疗载体(PPA/CQ)打破肿瘤细胞增殖与骨吸收之间的恶性循环,从而有效地治疗骨肿瘤.实验证明,PPA/CQ可以有效地富集到骨组织,...     

HA177-2A海水淡化蒸发塔结垢堵塞及清洗

某石化公司海水淡化装置的核心设备海水蒸发器,由于堵塞严重影响了装置的正常运行,分析了结垢的组成后提出了具体解决措施,在确保不损害设备的情况下进行了化学清洗.清洗效果理想,没有发生铝黄铜选择性腐蚀及点蚀,除垢率达到98%以上,达到了预期的目的.     

酚醛树脂弱凝胶驱注入速度的研究

注入速度是弱凝胶驱开发过程中重要的设计参数,选取成胶时间3d的酚醛树脂弱凝胶体系,考察了注入速度对弱凝胶驱油效果的影响.结果表明,随着注入速度增加,对低渗层易造成伤害,注入速度由1 mL/min提高至12 mL/min时,高渗层的分流率由33.7％增加至54.9％,高渗层封堵效果变差,提高采收率下降了7.74％.提出弱凝胶体系注入速度不宜过大.