阿帕替尼联合CCI-779体外抑制小细胞肺癌细胞株NCI-H446的增殖和迁移

背景与目的肺癌是世界上最常见的恶性肿瘤,其中小细胞肺癌是恶性程度最高的亚型,具有生长迅速、早期转移和高度血管化等特点。阿帕替尼(Apatinib)是我国自主研发的血管内皮生长因子受体2抑制剂,在多种实体瘤中疗效显著。本研究旨在探讨Apatinib对小细胞肺癌细胞株NCI-H446的体外作用以及联合哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)抑制剂CCI-779对小细胞肺癌的体外作用。方法体外培养小细胞肺癌细胞株NCI-H446,CCK8法、细胞凋亡实验、细胞周期实验及Transwell实验检测Apatinib及联合mTOR抑制剂CCI-779对NCI-H446细胞增殖、凋亡、周期及迁移的影响;Western blot实验检测血管内皮生长因子受体和细胞周期相关蛋白的表达。结果CCK8实验结果显示高浓度Apatinib能抑制NCI-H446细胞增殖;细胞凋亡实验结果显示高浓度Apatinib诱导NCI-H446细胞凋亡;Transwell实验结果显示高浓度Apatinib抑制NCI-H446细胞迁移;联合mTOR抑制剂CCI-779后,低浓度Apatinib便能抑制NCI-H446细胞增殖和迁移,诱导细胞凋亡。结论Apatinib对小细胞肺癌细胞株NCI-H446的作用具有浓度依赖性特征,高浓度Apatinib能够抑制NCI-H446细胞增殖和迁移,诱导细胞凋亡,与mTOR抑制剂CCI-779联用能增加NCI-H446细胞对Apatinib的敏感性。

基于TCGA数据库的EGFR突变型与野生型肺腺癌患者免疫微环境的差异性分析

背景与目的肺癌是一种具有高发病率与高死亡率的恶性肿瘤,腺癌是其中一个重要的组织亚型。表皮生长因子受体(epidermal growth factor receptor,EGFR)突变是肺腺癌患者重要的驱动基因。EGFR-酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)对EGFR敏感突变的患者疗效显著。而免疫治疗作为新兴的治疗却不能使EGFR突变患者获益,其中的机制研究尚不明确,并集中于EGFR与程序性死亡受体-配体1(programmed cell death-ligand 1,PD-L1)表达之上,而我们推测与两类患者不同的免疫微环境有关。方法从癌症基因组图谱(TheCancerGenome Atlas,TCGA)数据库收集肺腺癌数据集,下载临床信息资料及基因表达谱资料。通过TIMER2.0计算TCGA数据库中免疫相关淋巴细胞浸润情况。并对EGFR突变型与野生型患者进行基因集富集分析。结果临床特征分析显示EGFR突变更频繁发生于女性以及未吸烟患者中。免疫浸润分析显示EGFR突变患者通常具有更高的肿瘤相关成纤维细胞、普通髓系祖细胞、造血干细胞、效应CD4^(+)T细胞、自然杀伤T细胞浸润;具有更低的记忆B细胞、初始B细胞、浆细胞、浆细胞样树突状细胞、记忆CD4^(+)T细胞、CD4^(+)辅助性T细胞2、CD8^(+)T细胞、中心记忆CD8^(+)T细胞、初始CD8^(+)T细胞浸润。我们发现CD8^(^(+))T细胞、自然杀伤T细胞、记忆B细胞和造血干细胞在肿瘤中浸润的程度越高则患者预后越好(Log-rank检验,P=0.017、0.009,3、0.018和0.016)。同时CD4^(+)辅助性T细胞2在肿瘤中浸润的程度越高则患者预后越差(Log-rank检验,P=0.016)。基因集富集分析的结果显示,相比较EGFR野生型肺腺癌患者而言,EGFR突变患者的自然杀伤细胞介导的对肿瘤细胞的免疫应答的正调控、自然杀伤细胞激活参与免疫反应、在自然杀伤细胞介导的对肿瘤细胞的免疫应答这三条与自然杀伤细胞有关的通路上均处于下调状态,而参与免疫应答的细胞因子分泌的正调节这条通路为上调。结论EGFR突变患者肿瘤微环境缺乏有效的杀伤肿瘤的效应细胞并出现了效应细胞功能失调。这可能是EGFR突变患者免疫治疗疗效差的潜在原因。

MXene-based materials for electrochemical energy storage

Rechargeable batteries and supercapacitors are widely investigated as the most important electrochemical energy storage devices nowadays due to the booming energy demand for electric vehicles and hand-held electronics. The large surface-area-to-volume ratio and internal surface areas endow two-dimensional（2D） materials with high mobility and high energy density; therefore, 2D materials are very promising candidates for Li ion batteries and supercapacitors with comprehensive investigations. In 2011, a new kind of 2D transition metal carbides, nitrides and carbonitrides, MXene, were successfully obtained from MAX phases. Since then about 20 different kinds of MXene have been prepared. Other precursors besides MAX phases and even other methods such as chemical vapor deposition（CVD） were also applied to prepare MXene, opening new doors for the preparation of new MXene. Their 2D nature and good electronic properties ensure the inherent advantages as electrode materials for electrochemical energy storage. In this review, we summarize the recent progress in the development of MXene with emphasis on the applications to electrochemical energy storage. Also, future perspective and challenges of MXene-based materials are briefly discussed regrading electrochemical energy storage.

An effective method to screen sodium-based layered materials for sodium ion batteries

Due to the high cost and insufficient resource of lithium,sodium-ion batteries are widely investigated for large-scale applications.Typically,insertion-type materials possess better cyclic stability than alloy-type and conversion-type ones.Therefore,in this work,we proposed a facile and effective method to screen sodium-based layered materials based on Materials Project database as potential candidate insertion-type materials for sodium ion batteries.The obtained Na-based layered materials contains 38 kinds of space group,which reveals that the credibility of our screening approach would not be affected by the space group.Then,some important indexes of the representative materials,including the average voltage,volume change and sodium ion mobility,were further studied by means of density functional theory computations.Some materials with extremely low volume changes and Na diffusion barriers are promising candidates for sodium ion batteries.We believe that our classification algorithm could also be used to search for other alkali and multivalent ion-based layered materials,to accelerate the development of battery materials.

First‑principles computational insights into lithium battery cathode materials

Lithium-ion batteries(LIBs)are considered to be indispensable in modern society.Major advances in LIBs depend on the development of new high-performance electrode materials,which requires a fundamental understanding of their properties.First-principles calculations have become a powerful technique in developing new electrode materials for high-energy–den-sity LIBs in terms of predicting and interpreting the characteristics and behaviors of electrode materials,understanding the charge/discharge mechanisms at the atomic scale,delivering rational design strategies for electrode materials,etc.In this review,we present an overview of first-principles calculation methods and highlight their valuable role in contemporary research on LIB cathode materials.This overview focuses on three LIB cathode scenarios,which are divided by their cati-onic/anionic redox mechanisms.Then,representative examples of rational cathode design based on theoretical predictions are presented.Finally,we present a personal perspective on the current challenges and future directions of first-principles calculations in LIBs.

Dual-function redox mediator enhanced lithium-oxygen battery based on polymer electrolyte

The polymer electrolyte based lithium-oxygen battery has showed higher safety than that of organic liquid electrolyte.However,the energy efficiency and cycling stability are still the challenges for the practical application of lithium-oxygen battery.Herein,the 1,4 para benzoquinone has been demonstrated as dual-function redox mediator for promoting both oxygen reduction and oxygen evolution reactions of lithium-oxygen battery with polymer electrolyte,which have been confirmed by the Cyclic Voltammetry and discharge/charge test of battery under O_(2) gas,as well as the theoretical calculations.Furthermore,the composite cathode that in-situ constructed by polymerizing electrolyte precursors with redox me-diator can be beneficial for the electrochemical reactions.Combing composite cathode and lithium ions source,the polymer electrolyte based lithium-oxygen batteries can operate for long lifetime with low charge potentials and good rate performances.Thus,this work has highlighted the promising implementation of lithium-oxygen battery based on polymer electrolyte,in which the dual-function redox mediator are employed for both discharge and recharge processes.