ADAP2在胶质瘤患者中的预后价值及功能研究

目的分析ADAP2在脑胶质瘤中的预后价值和对胶质瘤迁移和侵袭的影响,并探索其可能机制。方法应用生物信息学分析ADAP2在胶质瘤中的差异性表达及其预后价值,并探索ADAP2对胶质瘤患者的潜在致癌机制。使用胶质瘤U87细胞系评估ADAP2敲除后对细胞迁移和侵袭的影响。结果ADAP2在恶性程度更高的胶质瘤亚型中富集,与免疫和炎症过程正相关,是胶质瘤患者的独立预后因素。敲低ADAP2后胶质瘤细胞的迁移和侵袭能力下降。结论ADAP2与胶质瘤的临床病理特征密切相关,通过与免疫细胞相互作用促进胶质瘤的进展,高表达ADAP2能促进胶质瘤细胞迁移和侵袭,是胶质瘤免疫治疗和精准诊断的潜在靶点。

ADAP2基因与肺鳞癌患者预后及肿瘤微环境免疫细胞浸润的关联研究

目的分析ADAP2基因与肺鳞癌患者预后及其与肿瘤微环境免疫细胞浸润的关联。方法下载TCGA(The Cancer Genome Atlas)数据库肺鳞癌患者临床信息和癌组织ADAP2基因转录水平,运用KM生存曲线和Cox比例风险模型分析ADAP2基因和患者预后的关联;采用xCell数据库分析ADAP2基因表达和肿瘤微环境免疫浸润的关系;利用免疫荧光双染实验观察ADAP2蛋白与M2型巨噬细胞标志物CD163的空间共定位。结果多因素Cox分析结果显示,ADAP2表达是肺鳞癌患者独立的预后因素,其高表达与肺鳞癌患者不良预后密切相关(HR=1.533,95%CI:1.139~2.064,P=0.005)。ADAP2基因与肿瘤微环境评分呈正相关(r=0.609,95%CI:0.550~0.661,P<0.001),与免疫评分也同样呈正相关(r=0.596,95%CI:0.536~0.650,P<0.001)。ADAP2基因与肺鳞癌单核吞噬细胞系统(巨噬细胞、巨噬细胞M1、巨噬细胞M2、单核细胞)的浸润呈高度正相关(r=0.737、0.718、0.603、0.631,P<0.001)。ADAP2与CD163存在共定位,主要表达于细胞膜。结论ADAP2有望成为预测肺鳞癌患者预后和免疫治疗效果的潜在生物标志物。

Crosstalk between innate and adaptive immunity in hepatitis B virus infection

Hepatitis B virus(HBV) infection is a major public healthproblem worldwide. HBV is not directly cytotoxic to infected hepatocytes; the clinical outcome of infection results from complicated interactions between the virus and the host immune system. In acute HBV infection, initiation of a broad, vigorous immune response is res-ponsible for viral clearance and self-limited inflammatory liver disease. Effective and coordinated innate and adaptive immune responses are critical for viral clearance and the development of long-lasting immunity. Chronic hepatitis B patients fail to mount efficient innate and adaptive immune responses to the virus. In particular, HBV-specific cytotoxic T cells, which are crucial for HBV clearance, are hyporesponsiveness to HBV infection. Accumulating experimental evidence obtained from the development of animal and cell line models has highlighted the importance of innate immunity in the early control of HBV spread. The virus has evolved immune escape strategies, with higher HBV loads and HBV protein concentrations associated with increasing impairment of immune function. Therefore, treatment of HBV infection requires inhibition of HBV replication and protein expression to restore the suppressed host immunity. Complicated interactions exist not only between innate and adaptive responses, but also among innate immune cells and different components of adaptive responses. Improved insight into these complex interactions are important in designing new therapeutic strategies for the treatment HBV infection. In this review, we summarize the current knowledge regarding the cross-talk between the innate and adaptive immune responses and among different immunocytes in HBV infection.

An adaptive method for high-resolution topology design

For the purpose of achieving high-resolution optimal solutions this paper proposes a nodal design variablebased adaptive method for topology optimization of continuum structures. The analysis mesh-independent density field, interpolated by the nodal design variables at a given set of density points, is adaptively refined/coarsened accord- ing to a criterion regarding the gray-scale measure of local regions. New density points are added into the gray regions and redundant ones are removed from the regions occupied by purely solid/void phases for decreasing the number of de- sign variables. A penalization factor adaptivity technique is employed-to prevent premature convergence of the optimiza- tion iterations. Such an adaptive scheme not only improves the structural boundary description quality, but also allows for sufficient further topological evolution of the structural layout in higher adaptivity levels and thus essentially enables high-resolution solutions. Moreover, compared with the case with uniformly and finely distributed density points, the proposed adaptive method can achieve a higher numerical efficiency of the optimization process.

The Process of Cross-cultural Adaptation:An Analysis of Outsourced

This paper employs Kim's(2001)‘Process of Cross-cultural Adaptation theory'to analyze the film—Outsourced,which talking about cross-cultural boundaries and how the protagonist Todd adapting to the Indian culture. Stress, adaptation and growth are three crucial phrases in the process of cross-cultural adaptation, which are correlated to each other and perform in a cyclic and continual way of‘draw-back-to-leap'. In this paper, each phrase is analyzed via employing theories and illustrating examples that Todd has experienced and encountered in India to highlight Todd's process of cross-cultural adaptation. Moreover, implications will be explored by the paper and suggestions will be offered to the sojourners for their better adaptation in the host country. In addition, the paper presents the differences between American culture and Indian culture, which are to some extent, the obstacles affecting successful cross-cultural adaptation.

TCR介导“inside-out”信号通路调控整合素的活化

整合素(integrin)是一类重要的跨膜黏附分子,在T细胞定向迁移到淋巴器官、感染或炎症部位以及T细胞与抗原呈递细胞(antigen presenting cell,APC)之间相互作用等过程中起重要作用。T细胞受到抗原或趋化因子等的刺激后,启动细胞内大量的信号传导分子,并形成"inside-out"信号通路,导致整合素构像的改变(conformation change)或促进整合素在细胞表面的聚集(integrinclustering),最终增强整合素的affinity或avidity,促进其与配体结合的能力,提高淋巴细胞间的黏附。近年来的研究已经鉴定出调控整合素活化的多个关键的信号分子及其形成的信号转导复合体。该文主要阐述T细胞受到抗原刺激后,由T细胞受体(T cell receptor,TCR)介导的"inside-out"信号通路中关键的信号分子如ADAP、SKAP-55、RapL、Rap1、Talin和Kindlins等如何与上下游信号分子协同作用,调控整合素LFA-1活化的分子机制。

ADAP restraint of STAT1 signaling regulates macrophage phagocytosis in immune thrombocytopenia

Heightened platelet phagocytosis by macrophages accompanied by an increase in IFN-γplay key roles in the etiology of immune thrombocytopenia(ITP);however,it remains elusive how macrophage-mediated platelet clearance is regulated in ITP.Here,we report that adhesion and degranulation-protein adaptor protein(ADAP)restrains platelet phagocytosis by macrophages in ITP via modulation of signal transducer and activator of transcription 1(STAT1)-FcγR signaling.We show that ITP was associated with the underexpression of ADAP in splenic macrophages.Furthermore,macrophages from Adap^(−/−)mice exhibited elevated platelet phagocytosis and upregulated proinflammatory signaling,and thrombocytopenia in Adap^(−/−)mice was mitigated by the depletion of macrophages.Mechanistically,ADAP interacted and competed with STAT1 binding to importinα5.ADAP deficiency potentiated STAT1 nuclear entry,leading to a selective enhancement of FcγRI/IV transcription in macrophages.Moreover,pharmacological inhibition of STAT1 or disruption of the STAT1-importinα5 interaction relieved thrombocytopenia in Adap^(−/−)mice.Thus,our findings not only reveal a critical role for ADAP as an intracellular immune checkpoint for shaping macrophage phagocytosis in ITP but also identify the ADAP-STAT1-importinα5 module as a promising therapeutic target in the treatment of ITP.

同时测定ADAP和 Lp/Ls 比值对胸腔积液的诊断价值

胸腔积液时通过胸膜活检,胸水细胞学、细菌学和活体组织检查,80%病人可确立病因诊断,但其余的20%仍需寻找鉴别恶性和良性胸腔积液的标记物以便了解预后。