Simultaneous Genetic Ablation of PD-1, LAG-3, and TIM-3 in CD8 T Cells Delays Tumor Growth and Improves Survival Outcome

Immune checkpoint inhibitors (ICI) represented a step forward in improving the outcome of patients with various refractory solid tumors and several therapeutic regimens incorporating ICI have already been approved for a variety of tumor entities. However, besides remarkable long-term responses, checkpoint inhibition can trigger severe immune-related adverse events in some patients. In order to improve safety of ICI as well as T cell therapy, we tested the feasibility of combining T cell-based immunotherapy with genetic disruption of checkpoint molecule expression. Therefore, we generated H-Y and ovalbumin antigen-specific CD8⁺ T cells with abolished PD-1, LAG-3, and TIM-3 expression through CRISPR/Cas9 technology. CD8⁺ T cells, subjected to PD-1, LAG-3, and TIM-3 genetic editing, showed a strong reduction in immune checkpoint molecule expression after in vitro activation, while no relevant reduction in responsiveness to in vitro stimulation was observed. At the same time, in B16-OVA tumor model, transferred genetically edited OT-1 CD8⁺ T cells promoted longer survival compared to control T cells and showed enhanced expansion without associated toxicity. Our study supports the notion that antigen-specific adoptive T cell therapy with concomitant genetic disruption of multiple checkpoint inhibitory receptors could represent an effective antitumor immunotherapy approach with improved tolerability profile.     

湿热处理技术对淀粉理化特性影响的研究进展

随着人们对变性淀粉需求量的增加,湿热处理技术成为了变性淀粉研究的热点之一。湿热处理是用于生产变性淀粉的一种物理手段,不带来任何化学试剂残留,属于环境友好型新技术。湿热处理可以改变淀粉的形态、结晶性、热学性质、淀粉胶性质,增加缓慢消化淀粉和抗性淀粉含量。为了促进湿热处理技术的研究、应用以及使人们对该技术有一个全面而清晰的认识,综述了湿热处理对淀粉理化性质和功能特性的影响,以及湿热处理淀粉在工业中的应用与发展前景。     

群体感应调控下的乳酸菌细菌素合成

细菌素是一种在新陈代谢过程中由核糖体合成的具有抑菌作用的抗菌肽,因此被作为天然、无毒抗菌剂并广泛应用到食品行业中。群体感应是细菌细胞间通过对自诱导物浓度的感知,从而对基因表达进行调控的行为,现已证明乳酸菌的群体感应是细菌素合成的关键调控机制。作者主要综述了目前乳酸菌细菌素的研究现状、细菌素的系统分类、群体感应信号的转导机制及其对乳酸菌细菌素合成的调节,以促进对细菌素的研究及应用。     

Force spectroscopy of polymers: Studying on intramolecular and intermolecular interactions in single molecular level

Single molecule force spectroscopy (SMFS) is a powerful means in studying the intramolecular and intermolecular interactions in polymer and supramolecular systems, thus opening new horizons for nanomechanic chemistry. This feature article concerns mainly how to employ AFM-based SMFS to obtain some of the important information which is not available by conventional characterizing methods, including single chain mechanics, the interfacial conformation and adhesive energy of polymers, interaction between macromolecules and small molecules, and the direct measurement of intermolecular forces. In addition, some of the recent advances in using the SMFS to bottom-up assembly of functional nanostructure are also discussed.     

分子设计在聚硅烷合成中的应用

采用分子设计的方法、通过理论计算,从分子结构学的角度解释了聚二甲基硅烷和聚甲基氢硅烷分子结构相似、但特性各异的原因。即聚甲基氢硅烷分子两个相邻扭曲角在势能最低点时的扭曲范围较大,其势能较大的区间较小,在大部分区域内聚甲基氢硅烷分子从一个构象转到另一个构象所需克服的势能很小;因此,聚甲基氢硅烷分子在有机溶剂中的伸展性好,溶解性好。相反,聚二甲基硅烷分子的势能在较大范围内都较高,聚二甲基硅烷分子的构象要到达这样的位置很困难;因此,聚二甲基硅烷的溶解特性较差。通过计算不同聚硅烷的势能面,可初步判断其溶熔特性的好坏。     

非肥胖型糖尿病小鼠胸腺异位基因及MHC-Ⅱ类分子的表达

目的研究非肥胖型糖尿病(NOD)小鼠胸腺异位基因及MHC-Ⅱ类分子表达水平,探讨胸腺异位基因及MHC-Ⅱ类分子在中枢免疫耐受中的作用。方法对NOD小鼠用GA-PAP试剂盒检测血糖;尿糖试纸检测尿糖;ELISA间接法检测IAA的含量;光镜观察胰岛的组织学改变情况;MTT法检测胸腺T淋巴细胞功能;ELISA夹心法检测胸腺细胞IL-4、IFN-γ分泌水平;流式细胞术检测胸腺细胞MHC-Ⅱ类分子表达水平;RT-PCR法检测胸腺异位基因的表达水平。结果NOD小鼠血糖水平与正常BALB/c小鼠差异无显著意义,尿糖水平均为阴性;NOD小鼠自身抗体水平与正常BALB/c小鼠差异无显著意义;与对照组相比,NOD小鼠胰岛数量减少,分布稀疏,胰岛细胞数亦减少,同时有大量炎细胞浸润;NOD小鼠胸腺细胞对ConA刺激的应答水平与正常BALB/c小鼠差异无显著意义;NOD小鼠胸腺细胞IFN-γ的分泌与正常BALB/c小鼠差异无显著意义,而IL-4的分泌能力明显低于正常BALB/c小鼠;NOD小鼠胸腺内Insulin水平显著减少,而GAD67和PLP水平无显著变化;NOD小鼠MHC-Ⅱ类分子的表达水平明显下降。结论NOD小鼠在糖尿病发病前期存在着胸腺异位基因及MHC-Ⅱ类分子表达缺陷,表明胸腺异位基因及MHC-Ⅱ类分子在中枢免疫耐受中起着重要作用。     

Therapeutic Targeting of the Gas6/Axl Signaling Pathway in Cancer

Many signaling pathways are dysregulated in cancer cells and the host tumor microenvironment. Aberrant receptor tyrosine kinase (RTK) pathways promote cancer development, progression, and metastasis. Hence, numerous therapeutic interventions targeting RTKs have been actively pursued. Axl is an RTK that belongs to the Tyro3, Axl, MerTK (TAM) subfamily. Axl binds to a high affinity ligand growth arrest specific 6 (Gas6) that belongs to the vitamin K-dependent family of proteins. The Gas6/Axl signaling pathway has been implicated to promote progression, metastasis, immune evasion, and therapeutic resistance in many cancer types. Therapeutic agents targeting Gas6 and Axl have been developed, and promising results have been observed in both preclinical and clinical settings when such agents are used alone or in combination therapy. This review examines the current state of therapeutics targeting the Gas6/Axl pathway in cancer and discusses Gas6- and Axl-targeting agents that have been evaluated preclinically and clinically.     

C与Si重构表面碰撞过程的分子动力学模拟

利用 Tersoff半经验多体相互作用势和分子动力学模拟方法研究了荷能 C原子与 Si(0 0 1) - (2× 1)重构表面碰撞动力学过程中入射 C原子能量随时间的变化情况 ,观察到了 C原子和表面 Si原子成键过程中 C原子的吸附、Si原子二聚键的打开、C原子的徙动以及 C、Si原子成键等物理过程 ,并对不同入射位置处入射 C原子和表面 Si原子碰撞过程中能量转移机理进行了分析。模拟结果表明 ,C原子相对于表面不同的局部构型发生不同的碰撞过程 ,而 C原子能量的提高有利于成键过程的发生 ,结果为 Si C在Si表面生长初期物理过程的认识提供了参考数据     

碘分子BⅡ0_u~+态荧光激发谱研究

本文以染料激光器的输出激发碘分子 ,采用荧光激发谱技术对碘分子 BΠ0 + u 态进行了实验研究 ,对所得荧光激发谱进行了标识 ,在此基础上计算了碘分子该态的分子常数 ,与理论值符合较好     

CaO水化法从钠硅渣中回收氧化钠的研究

采用二次回归正交设计回归出烧结法生产氧化铝中压脱硅钠硅渣常压氧化钙水化法脱钠的数学模型根据数学模型,按照单因子变动的原则,分别讨论了反应温度、石灰添加量、浆液液固比对钠硅渣脱钠率的影响并提出了在试验条件范围内,常压氧化钙水化法钠硅渣脱钠的最佳工艺条件是：温度95℃,CaO/Na2O分子比为5,浆液液固比取4。在此工艺条件下,钠硅渣脱钠率可达到95．2％。