Thrombospondin-1 CD47 Signalling: From Mechanisms to Medicine

Recent advances provide evidence that the cellular signalling pathway comprising the ligand-receptor duo of thrombospondin-1 (TSP1) and CD47 is involved in mediating a range of diseases affecting renal, vascular, and metabolic function, as well as cancer. In several instances, research has barely progressed past pre-clinical animal models of disease and early phase 1 clinical trials, while for cancers, anti-CD47 therapy has emerged from phase 2 clinical trials in humans as a crucial adjuvant therapeutic agent. This has important implications for interventions that seek to capitalize on targeting this pathway in diseases where TSP1 and/or CD47 play a role. Despite substantial progress made in our understanding of this pathway in malignant and cardiovascular disease, knowledge and translational gaps remain regarding the role of this pathway in kidney and metabolic diseases, limiting identification of putative drug targets and development of effective treatments. This review considers recent advances reported in the field of TSP1-CD47 signalling, focusing on several aspects including enzymatic production, receptor function, interacting partners, localization of signalling, matrix-cellular and cell-to-cell cross talk. The potential impact that these newly described mechanisms have on health, with a particular focus on renal and metabolic disease, is also discussed.     

Mutant p53 Mediates Sensitivity to Cancer Treatment Agents in Oesophageal Adenocarcinoma Associated with MicroRNA and SLC7A11 Expression

TP53 gene mutations occur in 70% of oesophageal adenocarcinomas (OACs). Given the central role of p53 in controlling cellular response to therapy we investigated the role of mutant (mut-) p53 and SLC7A11 in a CRISPR-mediated JH-EsoAd1 TP53 knockout model. Response to 2 Gy irradiation, cisplatin, 5-FU, 4-hydroxytamoxifen, and endoxifen was assessed, followed by a TaqMan OpenArray qPCR screening for differences in miRNA expression. Knockout of mut-p53 resulted in increased chemo- and radioresistance (2 Gy survival fraction: 38% vs. 56%, p < 0.0001) and in altered miRNA expression levels. Target mRNA pathways analyses indicated several potential mechanisms of treatment resistance. SLC7A11 knockdown restored radiosensitivity (2 Gy SF: 46% vs. 73%; p = 0.0239), possibly via enhanced sensitivity to oxidative stress. Pathway analysis of the mRNA targets of differentially expressed miRNAs indicated potential involvement in several pathways associated with apoptosis, ribosomes, and p53 signaling pathways. The data suggest that mut-p53 in JH-EsoAd1, despite being classified as non-functional, has some function related to radio- and chemoresistance. The results also highlight the important role of SLC7A11 in cancer metabolism and redox balance and the influence of p53 on these processes. Inhibition of the SLC7A11-glutathione axis may represent a promising approach to overcome resistance associated with mut-p53.     

基于多变量解耦控制的配电网单相接地故障集成化柔性消弧方法

随着静止无功补偿装置、柔性消弧装置、大功率逆变器等电力电子装备应用逐渐增多,配电网柔性化加快发展,但已有电力电子装备存在功能单一、成本高等问题.基于直流侧并接储能元件的直挂式级联H桥变流器,将多变量解耦控制方法与电流消弧方法相结合,实现柔性电力电子装备输出电流在dq0坐标系下的独立调节,使单套柔性电力电子装备同时集成配电网有功功率、无功功率双向流动控制,以及单相接地故障柔性消弧功能,有效提高电力电子装备的利用效率.理论分析以及功率控制和单相接地故障消弧建模仿真结果验证了所提方法的可行性.     

高温熔融-电感耦合等离子体原子发射光谱法测定含铁尘泥中5种有害元素

准确、快速地测定含铁尘泥中有害元素,对含铁尘泥节能降废项目研究及综合利用有着重要的指导意义。实验针对含铁尘泥试样因含碳量高,导致常规酸溶解方法如果不增加除碳步骤则很难完全分解试样的问题,采用高温熔融法将试样制成熔融液后倾倒于稀酸中溶解的方法,解决了碳含量高难溶解的问题。采用四硼酸锂-碳酸锂混合熔剂在高温下将试样熔融,熔融液高温倾倒于稀酸中制成澄清溶液,由于骤冷,试样炸裂成微小玻璃珠,无迸溅,操作简单,使得后续溶解过程快速完成,从而建立了电感耦合等离子体原子发射光谱(ICP-AES)测定P、Pb、K、Na、Zn共5种有害元素的方法。按照实验方法测定含铁尘泥中P、Pb、K、Na、Zn,测定值的相对标准偏差(RSD,n=9)在1.4%～5.7%之间,加标回收率在96%～110%之间。研究结果表明方法能够满足含铁尘泥样品中5种元素的定量分析要求。     

原位反应自发渗透法TiC／AZ91D镁基复合材料及AZ91D镁合金的拉伸变形与断裂行为

利用原位反应自发渗透技术合成了47．5％碳化钛TiC（体积分数，下同）增强AZ91D镁基复合材料，对比研究了该复合材料与铸态镁合金AZ91D基体的室温与高温拉伸变形行为，观察了拉伸断口微观组织形貌，并分析了这两种材料的断裂特征。结果表明，TiC／Mg复合材料具有良好的高温力学性能，在拉伸变形速率为0．001s^-1以及温度为723K，时其拉伸强度可达91．1MPa，而此时相同变形条件下的铸态AZ91D镁合金拉伸断裂强度只有41．1MPa，增幅达120％。而在室温下，镁基复合材料的拉伸断裂强度仅高出基体铸态镁合金23．4％。镁基复合材料的断裂应变较低，高低温时均表现为脆性断裂；而镁合金则由室温下的脆性断裂向高温下的韧性断裂过渡。     

磷对Ni3Al凝固组织的影响

磷(P)在Ni3Al中的溶解度很低，凝固过程中向剩余液体中偏聚，最终在晶界上析出富P相，凝固后期。P在剩余液体中的偏聚程度升高，降低形核率，抑制试样心部等轴晶的形成，促使试样外缘晶粒向心部延伸生长，增加柱状晶长度。P降低合金终凝温度，增如糊状区长度，阻碍液相补缩，增加形成疏松的倾向。P产生上述作用的根本原因是其降低固、液两相体积自由能差和原子跃迁穿过液／固界面的激活能。     

STUDY ON Ni-Cr SYSTEM SOLAR SELECTIVE THIN FILMS PREPARED BY MAGNETRON REACTIVE SPUTTERING PROCESS

1. IntroductionSolar selective thiIl solid fil1us are the key part for solar heat collect'ors. But ll1ostfactories still produced solar absorptive filn1s by traditional tecIl11ology sucl1 as pai1ltillga1ld electrocl1eluical process that nlust result in po…     

低碳钢中磷的偏聚与再结晶织构

本文用正、倒极图和ODF法研究了低碳钢板在不同冷轧和再结晶退火条件下,磷对再结晶织构的影响。用金相术、扫描电镜和电子探针研究了磷在钢中的分布和显微组织。结果发现,磷促进了与轧向平行的一组〈001〉和与轧面法向平行的一组〈111〉纤维织构的生成;这种作用与预退火温度密切相关,在390和590℃进行预退火就呈现,在490℃就抑制。在促进织构生成的预退火温度时产生晶内磷偏聚的异常显微组织。并认为这种纤维织构的形成与晶内磷偏聚有关。     

ZrB2-SiC基超高温陶瓷（UHTCs）的反应烧结及SHS粉体制备

用普通反应热压方法（RHP）和反应放电等离子体方法（R-SPS）原位反应制备了ZrB2-SiC，ZrB2-SiC—ZrC，ZrB2-SiC-ZrN，以及ZrB2-SiC-AIN4种复合材料。从密度，物相以及显微结构等方面比较了两种烧结方式之间的差别，对于升温速度较慢的普通热压方法，反应分步进行，显微结构不均匀；对于升温速度快的放电等离子体烧结，原料间的自蔓延反应被点着，反应速度快，显微结构均匀。同时以红外灯的热量为点火源，引发了Zr，Si及B4C间在空气气氛下的自蔓延反应，制备了较纯及粒径约为1μm的活性粉体。     

高温W/Re流口复合界面上的扩散层

W/Re流口在高温下使用时,复合界面处会发生反应扩散而形成一个由固溶体(W),双相σ,双相x,固溶体(Re)4个相组成的过渡层。并作出了不同反应扩散时间的浓度分布曲线,及浓度突变形成的双相区,从而确定了各相成份组成。对经反应扩散后的复合界面进行微观观察发现x相、σ相内有许多间隔式微裂纹,据此认为高温下W/Re流口失效原因是使用过程中上述两x,σ相内裂纹扩散,熔体渗入所致。