Structural Cues for Understanding eEF1A2 Moonlighting

Spontaneous mutations in the EEF1A2 gene cause epilepsy and severe neurological disabilities in children. The crystal structure of eEF1A2 protein purified from rabbit skeletal muscle reveals a post-translationally modified dimer that provides information about the sites of interaction with numerous binding partners, including itself, and maps these mutations onto the dimer and tetramer interfaces. The spatial locations of the side chain carboxylates of Glu301 and Glu374, to which phosphatidylethanolamine is uniquely attached via an amide bond, define the anchoring points of eEF1A2 to cellular membranes and interorganellar membrane contact sites. Additional bioinformatic and molecular modeling results provide novel structural insight into the demonstrated binding of eEF1A2 to SH3 domains, the common MAPK docking groove, filamentous actin, and phosphatidylinositol-4 kinase IIIβ. In this new light, the role of eEF1A2 as an ancient, multifaceted, and articulated G protein at the crossroads of autophagy, oncogenesis and viral replication appears very distant from the “canonical” one of delivering aminoacyl-tRNAs to the ribosome that has dominated the scene and much of the thinking for many decades.     

Synthesis of Diamond@SiO2@Ag composite materials for high SERS effect

Among various carbon materials, diamond stands out due to excellent physical and chemical properties. In this work, we designed Dia@SiO₂@Ag composites combining diamond micropowder and Ag nanoparticles by a simple chemical method and obtained stable substrate for surface enhanced Raman scattering (SERS) owing to its high surface-to-volume ratio, low density, as well as close bond between diamond and Ag. As-prepared Dia@SiO₂@Ag presented high activity to detect crystal violet and rhodamine 6G molecules, which was demonstrated by significantly enhanced SERS spectra and high enhancement factor values (10⁸-10⁹). Moreover, Dia@SiO₂@Ag also showed desired sensitivity, which was investigated by detection limit. Therefore, our study provided more theoretical support and broadened the functional applications of diamond, particularly in Raman detection.     

Supramolecular Glyco‐nanoparticles Toward Immunological Applications

Glyco‐mimicking nanoparticles (glyco‐NPs) with Förster resonance energy transfer (FRET) donor and acceptor groups formed via dynamic covalent bond of benzoboroxole and sugar from two complementary polymers are prepared. The glyco‐NPs are proved to be quite stable under physiological conditions but sensitive to pH. So the glyco‐NPs can be internalized by dendritic cells with integrity and nontoxicity and then dissociate within the acidic organelles. This particle dissociation is directly observed and visualized in vitro, for the first time via the FRET measurements and fluorescent microscopy. This feature makes controlled release of drug or protein by glyco‐NPs possible, i.e., when model antigen Ovalbumin is loaded in the glyco‐NPs, the released Ovalbumin in dendritic cells stimulates T cells more efficiently than the free Ovalbumin itself as a result of the enhanced antigen processing and presentation. Thus, the results enlighten a bright future of the glyco‐NPs in immunotherapy.     

网络安全威胁因素及其常见网络安全技术分析

社会经济的快速发展促进了科学技术水平的显著提升，社会生产生活各个领域当中对计算机网络的应用程度不断提升，当前，网络已经成为了人们日常生活与工作的重要组成部分。为此，加强对网络安全等因素影响研究就显得格外重要。网络环境关系着用户的使用质量，更加影响人们的工作效率，加强对网络安全技术的研究时解决相关问题的核心内容。本文针对网络安全威胁因素以及常见的网络安全技术进行了简要分析。     

Preliminary Evidence on the Diagnostic and Molecular Role of Circulating Soluble EGFR in Non-Small Cell Lung Cancer

Assessment of biological diagnostic factors providing clinically-relevant information to guide physician decision-making are still needed for diseases with poor outcomes, such as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) is a promising molecule in the clinical management of NSCLC. While the EGFR transmembrane form has been extensively investigated in large clinical trials, the soluble, circulating EGFR isoform (sEGFR), which may have a potential clinical use, has rarely been considered. This study investigates the use of sEGFR as a potential diagnostic biomarker for NSCLC and also characterizes the biological function of sEGFR to clarify the molecular mechanisms involved in the course of action of this protein. Plasma sEGFR levels from a heterogeneous cohort of 37 non-advanced NSCLC patients and 54 healthy subjects were analyzed by using an enzyme-linked immunosorbent assay. The biological function of sEGFR was analyzed in vitro using NSCLC cell lines, investigating effects on cell proliferation and migration. We found that plasma sEGFR was significantly decreased in the NSCLC patient group as compared to the control group (median value: 48.6 vs. 55.6 ng/mL respectively; p = 0.0002). Moreover, we demonstrated that sEGFR inhibits growth and migration of NSCLC cells in vitro through molecular mechanisms that included perturbation of EGF/EGFR cell signaling and holoreceptor internalization. These data show that sEGFR is a potential circulating biomarker with a physiological protective role, providing a first approach to the functional role of the soluble isoform of EGFR. However, the impact of these data on daily clinical practice needs to be further investigated in larger prospective studies.     

Cell Sheet Comprised of Mesenchymal Stromal Cells Overexpressing Stem Cell Factor Promotes Epicardium Activation and Heart Function Improvement in a Rat Model of Myocardium Infarction

Cell therapy of the post-infarcted myocardium is still far from clinical use. Poor survival of transplanted cells, insufficient regeneration, and replacement of the damaged tissue limit the potential of currently available cell-based techniques. In this study, we generated a multilayered construct from adipose-derived mesenchymal stromal cells (MSCs) modified to secrete stem cell factor, SCF. In a rat model of myocardium infarction, we show that transplantation of SCF producing cell sheet induced activation of the epicardium and promoted the accumulation of c-kit positive cells in ischemic muscle. Morphometry showed the reduction of infarct size (16%) and a left ventricle expansion index (0.12) in the treatment group compared to controls (24–28%; 0.17–0.32). The ratio of viable myocardium was more than 1.5-fold higher, reaching 49% compared to the control (28%) or unmodified cell sheet group (30%). Finally, by day 30 after myocardium infarction, SCF-producing cell sheet transplantation increased left ventricle ejection fraction from 37% in the control sham-operated group to 53%. Our results suggest that, combining the genetic modification of MSCs and their assembly into a multilayered construct, we can provide prolonged pleiotropic effects to the damaged heart, induce endogenous regenerative processes, and improve cardiac function.     

腹腔手术后重症患者心肌损伤的危险因素

目的探讨腹腔手术后重症患者心肌损伤的发生情况及可能的危险因素。方法回顾性分析北京大学人民医院2017年1月至2019年1月腹腔手术后重症患者的一般临床资料及心肌损伤情况,收集并观察基础病史、术中(手术时间、是否急诊手术、术中出血>800 ml和术中低血压等)及术后指标(改良氧合指数、血乳酸、急性肾损伤和术后24 h内使用升压药情况等)。根据术后是否发生心肌损伤,将患者分为心肌损伤组和非心肌损伤组,采用Logistic回归分析腹腔手术后重症患者心肌损伤的危险因素。结果在纳入的803例腹腔手术后重症患者中,心肌损伤发生率为17. 2%(138/803),而急性心肌梗死发生率仅为0. 9%(7/803)。单因素分析显示,慢性肾功能不全病史、手术时间、急诊手术、术中低血压、术后24 h内使用升压药、高APACHEⅡ评分及术后即刻急性肾损伤与术后重症患者心肌损伤相关(P<0. 05)。多因素回归分析显示,急诊手术(OR=3. 14,95%CI:1. 76～5. 60,P<0. 001)、术后24 h内使用升压药(OR=2. 26,95%CI:1. 23～4. 15,P=0. 008)、APACHEⅡ评分(OR=1. 05,95%CI:1. 01～1. 09,P=0. 008)和术后急性肾损伤(OR=3. 18,95%CI:1. 78～5. 69,P <0. 001)与腹腔手术后重症患者发生心肌损伤独立相关。结论重症患者腹腔手术后心肌损伤发生率高,急诊手术、术后24 h内使用升压药、高APACHEⅡ评分和术后急性肾损伤是导致腹腔手术后重症患者发生心肌损伤的独立危险因素。     

因素空间理论下基点分类算法研究

目前，基于因素空间理论的背景基提取算法计算过程复杂，初始化必须依赖各因素极值，基点数量提取冗余等原因，未能在应用中取得很好效果。为此，结合内点判别法和知识可继承、可扩展的思想，提出一种计算简单、初始化独立、基点数量小的改进的背景基提取算法。然后，利用改进的背景基提取算法构造出一种全新的数据分类算法-基点分类算法，基点分类算法以提取每一类样本的背景基为预测模型，再通过新定义的λ-背景基，优化预测模型。数值实验表明:基点分类算法原理简单、构造难度小、分类模型泛化能力强，预测能力准确率高，同时严格的模型限定区域又能为识别新类别提供新方法。     

动态高压微射流处理对方竹笋膳食纤维理化及结构特性的影响

以方竹笋中提取的膳食纤维为研究对象，采用动态高压微射流（dynamic high-pressure micro-fluidization, DHPM）在不同压力条件（0，50，100，150，200 MPa）下进行处理，探究其对竹笋膳食纤维（bamboo shoots dietary fiber, BSDF）理化和结构特性的影响。结果表明，随着处理压力的增大，BSDF粒径先增大后减小，当处理压力为150 MPa时，粒径最小，为（370±11） nm，此条件下BSDF的持水力、持油力和膨胀力达到最大，较对照组分别提高了47.74%，50.54%，61.27%，且差异显著（P<0.05）。红外光谱分析表明DHPM处理不会改变BSDF的官能团，但会使BSDF内部的部分氢键断裂和半纤维素、木质素等发生降解；X射线衍射和热重分析表明DHPM处理不会引起BSDF的晶体结构改变，但晶体有序度会下降，进而导致其热稳定性降低；微观结构分析显示DHPM处理会使BSDF颗粒尺寸减小、表面粗糙、组织松散，且当处理压力为200 MPa时，颗粒发生团聚。综上，DHPM可以有效改善BSDF的理化性质，在膳食纤维改性方面具有一定的应用价值。