Activation of Stimulation of Interferon Genes (STING) Signal and Cancer Immunotherapy

Stimulator of interferon gene (STING), an intracellular receptor in the endoplasmic reticulum, could induce the production of cytokines such as type I interferon (IFN) by activating the cGAS-STING signal pathway. In recent years, activation of STING has shown great potential to enhance anti-tumor immunity and reshape the tumor microenvironment, which is expected to be used in tumor immunotherapy. A number of STING agonists have demonstrated promising biological activity and showed excellent synergistic anti-tumor effects in combination with other cancer therapies in preclinical studies and some clinical trials. The combination of STING agonists and ICI also showed a potent effect in improving anti-tumor immunity. In this review, we introduce the cGAS-STING signaling pathway and its effect in tumor immunity and discuss the recent strategies of activation of the STING signaling pathway and its research progress in tumor immunotherapy.     

PEG型酸性温控离子液体中芳香酸和醇的酯化反应

报道了该催化体系在芳香酸和醇酯化反应中的应用. 研究发现, 该离子液体具有优良的催化性能, 产品易分离, 催化剂可循环使用且活性不降低, 催化剂不易流失, 实现了均相催化剂的高效回收和再利用.     

表面活性剂对完全液相法制Cu-Zn-Al浆状催化剂结构和性能的影响

采用完全液相法制备了Cu-Zn-Al双功能浆状催化剂, 利用不同类型表面活性剂对其进行了修饰和改性. 通过N2气吸附、XRD和XPS等方法考察了表面活性剂类型对催化剂织构、物相以及表面性质的影响, 采用浆态床反应装置对其合成气一步法制备二甲醚的催化活性进行了评价, 讨论了催化剂结构与性能的关系. 结果表明, 表面活性剂主要是通过与活性金属的作用调节催化剂的表面性质、孔结构、相结构以及晶粒大小, 进而影响催化剂的催化活性; 非离子表面活性剂总体上对催化剂的性能有促进作用, 阳离子表面活性剂和阴离子表面活性剂对催化剂性能存在不利影响; 表面活性剂与活性金属作用的强弱是影响性能的关键.     

单分子流式检测仪的研制

采用激光诱导荧光和流体动力学聚焦技术成功地研制出单分子流式检测仪, 实现了对水溶液中单个藻红蛋白及单个DNA分子片段的检测, 检测速率可达到每秒几十次. 与单分子荧光显微术相比, 流式分析将固定的标本台改为流动的单分子悬液, 大大提高了检测速率和统计精确性, 更加适合生物样品的快速、超高灵敏分析.     

Ti,Na与O2反应机理的理论研究

基于MP2/6-311+G(d)水平, 分别对过渡金属Ti和碱金属Na与O2的反应机理进行了研究. 比较了Ti和Na分别以垂直O—O键和沿着O—O键的方向逼近O2, 以及中性体系Ti/Na+O2和带1个负电荷的体系(Ti/Na+O2)-的情况. 详细分析了不同反应路径的结合能和电荷变化的曲线, 预测了最佳反应方式. 结果表明, 垂直接近方式要比水平接近方式更具有优势; 体系带一个负电荷(Ti/Na+O2)-有利于金属与O2的结合. 同时, 计算结果表明在Ti+O2和(Ti+O2)-体系中Ti容易与单态的O2结合; 在中性体系中Na也容易与单态O2结合, 而在(Na+O2)-体系中Na与三态O2的结合更稳定. 在CCSD(T)/6-311++G(3df)//MP2/6-311+G(d)水平下, 计算了Ti+O2和(Ti+O2)-的反应势能面.     

Establishment of a Tumor-bearing Mouse Model Stably Expressing EGFP Labeled Human MUC1 VNTRs

Two eukaryotic vectors expressing 9 tandem repeats of human MUCI（VNTR）, VR1012-VNTR, and pEGFP-VNTR, were constructed by cloning VNTR gene into VR1012 and pEGFP, respectively. VNTR stably expressing murine Lewis lung carcinoma（LLC） cell line（VNTR^＋ LLC） was established by Lipofectamine-mediated transfection of pEGFP-VNTR into LLC cells. The EGFP expression was observed under a fluorescent microscope and VNTR expression in VNTR^＋ LLC cells was confirmed by means of Western blotting. A syngenic graft tumor model was generated by subcutaneous injection of VNTR^＋ LLC cells into C57/BL6 mice and tumor size increased rapidly with time and in a cell qumber dependent manner. VNTR mRNA expression in the tumor formed was confirmed by RT-PCR. After the third immunization mice were challenged subcutaneously with 5×10^5 VNTR^＋ LLC cells, a significant reduction of subcutaneous tumor growth was observed in the groups immunized with VNTR plasmid DNA compared with that in the groups immunized with the vector DNA alone. Thus, the suppression of subcutaneous tumor was antigen-specific. This model is useful for the development of tumor vaccines targeting MUCI VNTRs.     

Construction and Expression of Human Survivin and Preparation of Its Polyclonal Antibody

Survivin, a novel member of inhibitor of apoptosis（IAP） protein family, is aberrantly expressed in cancer but undetectable in normal, differentiated adult tissues. The cancer-specific expression of survivin, coupled with its importance in inhibiting cell death and in regulating cell division makes it a useful diagnostic marker of cancer and a potential target for cancer treatment. Survivin cDNA amplified from the total RNA of 293 cells through RT-PCR was cloned into prokaryotic expression vector pRSET-B. The recombinant plasmid pRSET-B-Surv was expressed in E.coli BL21, and the relative molecule mass（Mr） of expressed fusion protein was approximately 21000. The recombinant protein was purified through Ni^2＋ affinity chromatography column and characterized by SDS-PAGE and Western blot. The purified recombinant protein was then injected into rabbits, and antisurvivin polyclonal antibody with a high titer was obtained.     

Electrochemical Immunoassay for Tumor Marker CA19-9 Detection Based on Self-Assembled Monolayer

A CA19-9 electrochemical immunosensor was constructed using a hybrid self-assembled membrane modified with a gold electrode and applied to detect real samples. Hybrid self-assembled membranes were selected for electrode modification and used to detect antigens. First, the pretreated working electrodes were placed in a 3-mercaptopropionic acid (MPA)/β-mercaptoethanol (ME) mixture for 24 h for self-assembly. The electrodes were then placed in an EDC/NHS mixture for 1 h. Layer modification was performed by stepwise dropwise addition of CA19-9 antibody, BSA, and antigen. Differential pulse voltammetry was used to characterize this immunosensor preparation process. The assembled electrochemical immunosensor enables linear detection in the concentration range of 0.05–500 U/mL of CA19-9, and the detection limit was calculated as 0.01 U/mL. The results of the specificity measurement test showed that the signal change of the interfering substance was much lower than the response value of the detected antigen, indicating that the sensor has good specificity and strong anti-interference ability. The repeatability test results showed that the relative standard deviations were less than 5%, showing good accuracy and precision. The CA19-9 electrochemical immunosensor was used for the actual sample detection, and the experimental results of the standard serum addition method showed that the RSD values of the test concentrations were all less than 10%. The recoveries were 102.4–115.0%, indicating that the assay has high precision, good accuracy, and high potential application value.     

Deep Multilabel Multilingual Document Learning for Cross-Lingual Document Retrieval

Cross-lingual document retrieval, which aims to take a query in one language to retrieve relevant documents in another, has attracted strong research interest in the last decades. Most studies on this task start with cross-lingual comparisons at the word level and then represent documents via word embeddings, which leads to insufficient structure information. In this work, the cross-lingual comparison at the document level is achieved through the cross-lingual semantic space. Our method, MDL (deep multilabel multilingual document learning), leverages a six-layer fully connected network to project cross-lingual documents into a shared semantic space. The semantic distances can be calculated when the cross-lingual documents are transformed into embeddings in semantic space. The supervision signals are automatically extracted from the data and then used to construct the semantic space via a linear classifier. The ambiguity of manual labels could be avoided and the multilabel supervision signals can be acquired instead of a single label. The representation of the semantic space is enriched by multilabel supervision signals, which improves the discriminative ability of the embeddings. The MDL is easy to extend to other fields since it does not depend on specific data. Furthermore, MDL is more efficient than the models training all languages jointly, since each language is trained individually. Experiments on Wikipedia data showed that the proposed method outperforms the state-of-the-art cross-lingual document retrieval methods.     

聚合物气体辅助注射成型制品的形态结构

作为一种由常规注射成型发展起来的聚合物加工技术,气体辅助注射成型具有节约原材料、缩短成型周期以及提高制品性能等优点,已得到广泛的应用.由于气辅成型过程是一个在刚、柔双重约束界面条件下进行的多相复杂体系的多次流动过程,因而其形态结构的形成、发展和演化要远比常规注塑成型复杂.然而在气辅成型的形态结构方面,国内外的研究一直以来开展得较少.近年来,作者在聚合物及其共混物、复合材料气辅成型制品的形态结构方面已开展了广泛的研究工作,本文对这些工作和一些重要结果作了总结,并简要分析了成型过程中剪切场对形态演化的影响,最后对该研究方向的发展趋势作了展望.