A Certain Concentration of Serum Promotes Human OA Chondrocyte Survival by Increasing the Level of Autophagy

目的：欧凯疗法（Orthokine）是一种通过自体条件血清关节腔内注射治疗骨性关节炎（OA）的新型治疗方法。本文旨在明确不同浓度血清对人OA软骨细胞自噬作用的影响以及其对人OA软骨细胞的保护作用，并探讨一定浓度血清促进人OA软骨细胞存活的相关机制，为欧凯疗法提供一定的理论依据。 方法：1、在OA患者全膝关节置换术的术中取关节软骨，分离培养人OA软骨细胞，并以甲苯胺蓝及免疫组化法进行细胞鉴定。2、WesternBlotting法检测0%、1%、5%、10%、20%五种浓度血清培养的人OA软骨细胞细胞外基质相关蛋白（Aggrecan、II型胶原、TIMP、MMP13）的表达。3、WesternB...Introduction: Intraarticular injection of autologous conditioned serum, which called Orthokine is a new treatment of osteoarthritis (OA). We aimed to investigate the effect of different concentration of serum on the autophagy of human OA chondrocytes and wheather it can protect human OA chondrocytes from matrix degradation in order to provide the theoretical foundation for Orthokine. Methods: Hu...学位：医学硕士院系专业：医学院_外科学学号：2452011115340

Assembling Hollow Carbon Sphere-Graphene Polylithic Aerogels for Thermoelectric Cells

Aerogels are highly porous bulk materials assembled chemically or physically with various nanoscale building blocks and thus hold promise for numerous applications including energy storage and conversion. Assembling of hollow or porous particles with the diameter larger than 100 nm into hierarchically porous aerogels is efficient but challenging for achieving a high specific surface of aerogel. In this regard, submicron-sized carbon spheres with hollow cores and microporous shells are assembled into bulk aerogels, for the first time, in the presence of two-dimensional graphene sheets as special cross-linkers. The resulting bead-to-sheet polylithic aerogels show ultra-low density (51–67 mg cm−3), high conductivity (263–695 S m−1) and high specific surface area (569–609 m2 g−1). An application of thermocells is demonstrated with maximum output power of 1.05 W m−2 and maximum energy conversion efficiency of 1.4% relative to Carnot engine, outperforming the current simple U-shaped thermocells reported elsewhere

杂交元零能模式抑制的正交基本变形模式方法

通过杂交元位移场直接推导了单元基本变形模式,并且采用联合正交条件提出一种新的正交化方法,所得到的正交基本变形模式不仅具有简单的变形特征而且和材料参数无关,可以方便有效地考察单元性能,为评价不同杂交元提供了一个统一的参考标准.在此基础上利用柔度矩阵正定性给出一种简单有效的零能模式识别方法,并进一步利用基本变形模式和初始应力模式之间耦合关系,提出一种抑制杂交元零能模式的假设应力场方法,同时指出基本变形模式正交性是抑制单元零能模式的充分必要条件.2D-4节点和3D-8节点单元的数值算例说明了该文基本变形模式方法的有效性

热处理对C/SiC复合材料纤维束中微裂纹扩展行为的影响

利用透射电镜(TEM)观察了湿氧气氛热处理对3D C/SiC复合材料纤维束中微裂纹扩展的影响规律。研究表明,在未经热处理的3D C/SiC纤维束中,微裂纹传播主要为沿纤维/界面相脱粘的单一模式;热处理后纤维束中的微裂纹形成了多种扩展模式。在经历了长达100h的保温之后,热解碳的部分有序化及其层状结构的形成是导致裂纹能量耗散模式增加的主要因素,有序结构的形成也增加了裂纹的联通和长裂纹形成的几率

Determination of Phenolic Endocrine Disrupting Chemicals in Human Urine by High Performance Liquid Chromatography Tandem Electrospray Ionization Mass Spectrometry

采用通用电喷雾离子源的高效液相色谱-串联质谱(HPlC-ESI MS/MS)分析技术,通过丹磺酰氯衍生化处理,建立了同时测定人尿液中双酚A(bPA)、三氯生(TCS)、炔雌酮(EE2)、雌酮(E1)、雌二醇(E2)5种酚类内分泌干扰物的高灵敏方法。5种酚类化合物在0.2~100μg/l质量浓度范围内线性关系良好,相关系数(r2)均在0.99以上,检出限(lOd)在0.02~0.27μg/l之间。在5、10、50μg/l加标水平下,平均回收率为85%~125%,相对标准偏差(rSd,n=3)为0.53%~14.4%。该方法灵敏度高、重现性好、回收率高、操作简单,可作为人尿液中酚类内分泌干扰物暴露分析的备选方法之一。A high performance liquid chromatography tandem electrospray ionization mass spectrometry(HPLC-ESI MS/MS) method was developed and validated for the determination of phenolic endocrine disrupting chemicals(EDCs),including bisphenol A(BPA),triclosan(TCS),17α-ethynylestradiol(EE2),estrone(E1) and 17 β-estradiol(E2)in human urine.The samples were purified by liquid-liquid extraction,derivertized with dansyl chloride,and detected by HPLC-ESI MS/MS.The target compounds were quantified by the stable isotope dilution technique.The calibration curve were linear in the range of 0.2-100 μg/L for the 5 EDCs with correlation coefficients more than 0.99.The limits of detection of 5 EDCs were in the range of 0.02-0.27 μg/L.The matrix recoveries of the method for 5 EDCs at three spiked levels of 5,10 and 50 μg/L ranged from 85% to 125%.The relative standard deviations(RSDs,n=3) were between 0.53% and 14.4%.The method was successfully applied in the analysis of 5 EDCs in human urine with its sensitivity and accurancy.中科院“百人计划”项目; 厦门市科技计划项目(3502Z20122003

连续含铝SiC自由膜的制备与发光特性研究

通过自制喷膜装置对聚铝碳硅烷(PACS)进行脱泡处理、熔融纺膜,并对其进行氧化交联、高温预烧及高温裂解终烧可制得连续含铝SiC自由薄膜。用扫描电镜(SEM)分析薄膜的形貌,通过红外光谱(FT-IR)分析氧化交联后薄膜的结构变化,通过电子探针(EPMA)、拉曼光谱(Raman)、X射线衍射(XRD)与场发射高分辨透射电子显微镜(HRTEM)对薄膜进行成分及微观结构分析,采用光致发光谱(PL)对薄膜的光学带隙和发光特性进行了研究。结果表明,熔融纺膜法与PACS先驱体法相结合可制得均匀、致密的耐高温连续含铝SiC自由薄膜,室温下表现出了320~440nm宽谱带发光,其发光峰可分别归因于-αSiC和C簇,且随着烧结温度的提高,发光强度增大

CVI B-C基体改性2D C/SiC在低温湿氧中的自愈合行为

针对C/SiC低温氧化易失效的不足,研究了CVI B-C基体改性2D C/SiC在700℃湿氧中100MPa下加载至60h的氧化行为,利用SEM和TEM观察了改性材料不同服役时间的微结构特征,揭示了演变规律.研究表明,CVI B-C基体改性使C/SiC低温抗氧化能力显著提升.基体裂纹及其在应力加载下的开裂均为氧化气体提供进入通道,而后可被B-C氧化产物B2O3封填,抑制内部C消耗.CVI B-C与其氧化产物一同参与缺陷愈合.在60h内,B-C改性层愈合能力尚未完全发挥,可服役更长时间

ATR/Chk1 signaling induces autophagy through sumoylated RhoB-mediated lysosomal translocation of TSC2 after DNA damage

RhoB作为抑癌蛋白通过诱导肿瘤细胞的凋亡在抑制肿瘤的发生发展中发挥着重要作用，并且与肿瘤耐药性密切相关，但关于RhoB如何促进细胞死亡的分子机理的研究仍不清楚。在本研究中，该团队发现在DNA单链损伤情况下，ATR-Chk1信号通路的激活，会使RhoB被Chk1磷酸化，该磷酸化修饰会使RhoB从细胞质膜解离下来进入细胞质中，进而被SUMO化修饰。SUMO化修饰后的RhoB会与TSC2形成复合物，并将TSC2复合物带到溶酶体上，引起细胞自噬的发生。 该文共同第一作者为刘明冬、曾涛玲和张新，通讯作者为王洪睿教授和赵同金教授。【Abstract】DNA damage can induce autophagy; however, the underlying mechanism remains largely unknown. Here we report that DNA damage leads to autophagy through ATR/Chk1/RhoB-mediated lysosomal recruitment of TSC complex and subsequent mTORC1 inhibition. DNA damage caused by ultraviolet light (UV) or alkylating agent methyl methanesulphonate (MMS) results in phosphorylation of small GTPase RhoB by Chk1. Phosphorylation of RhoB enhances its interaction with the TSC2, and promotes its sumoylation by PIAS1, which is required for RhoB/TSC complex to translocate to lysosomes. As a result, mTORC1 is inhibited, and autophagy is activated. Knockout of RhoB severely attenuates lysosomal translocation of TSC complex and the DNA damage-induced autophagy. Reintroducing wild-type but not sumoylation-resistant RhoB into RhoB−/− cells restores the onset of autophagy. Hence, our study identifies a molecular mechanism for translocation of TSC complex to lysosomes in response to DNA damage, which depends on ATR/Chk1-mediated RhoB phosphorylation and sumoylation.This work was supported by the National Natural Science Foundation of China (U1605222, 81472459, 31671223), the National Key Research and Development Project of China (2016YFC1302400, 2016YFA0502003), the Fundamental Research Funds for the Central Universities (20720140550, 20720160070), the National Science Foundation for Fostering Talents in Basic Research of the National Natural Science Foundation of China (J1310027), the Project 111 sponsored by the State Bureau of Foreign Experts and Ministry of Education (B12001), the National Natural Science Foundation of China (31601132) to T.Z., the National Natural Science Foundation of China (81402290) to Q.L., and the National Natural Science Foundation of China (U1405223) to X.D

舒林酸衍生物K-80003与MEK抑制剂考比替尼联合用药对乳腺癌的效果研究

目的舒林酸衍生物K-80003是全球首个以类维甲酸受体的截断形式(该文简称tRXRα)为靶点的原创候选新药。本课题组前期研究发现,K-80003在抑制乳腺癌的同时,在乳腺癌细胞中可以激活p-ERK,因此该文试图将K-80003与已上市的MEK抑制剂考比替尼(cobimetinib,GDC-0973)联合使用,探究其对乳腺癌的抑制效果是否增强。方法采用Western blot法、MMTV-PyMT乳腺癌转基因小鼠模型、免疫组化染色等方法,检测K-80003与GDC-0973联合用药对乳腺癌细胞内ERK信号通路及肿瘤细胞凋亡水平的影响。结果 K-80003与GDC-0973联合使用可以更好地抑制p-ERK,并促进PARP切割,导致乳腺癌细胞凋亡,K-80003与GDC-0973联合使用相比于K-80003单药使用,对肿瘤细胞增殖的抑制作用有明显统计学意义。结论舒林酸衍生物K-80003与MEK抑制剂GDC-0973联合使用呈现一定的协同促进乳腺癌细胞凋亡作用。国家自然科学基金资助项目(No 91429306