摘要：T lymphocytes are crucial for antiviral responses and provide a promising repertoire for potential therapies of viral diseases such as cytomegalovirus(CMV)infection1 and the ongoing COVID-19 pandemic caused by SARS-CoV-2.^(2) CMV-related diseases occur once the host immune system is impaired or lacks a protective repertoire of virus-specific T lymphocytes.3 Adoptive transfer of T-cell receptor(TCR)-engineered T cells(TCR-Ts)provides an encouraging alternative treatment option for patients with CMV reactivation.^(4) However,generating TCR-Ts requires the identification of epitope-specific and functional TCR *** single-cell sequencing techniques open up the ability to unravel TCR repertoires,^(5 )which offers a potential opportunity to screen functional TCR pairs for TCR-T ***,we report an efficient approach that combines ex vivo CD8+T-cell stimulation with single-cell RNA and TCR V(D)J sequencing to identify CMV-specific TCRs for generating TCR-Ts.

摘要：复合材料挖补修复强度优化研究中，广泛使用有限元方法寻优导致优化效率低下，对多参数协同优化也探究不足。为解决上述问题，本文针对复合材料阶梯修复提出了一款多参数联合优化程序（cooperative repair parameter optimization program, CRPOP）。程序将解析与数值方法结合，代替有限元计算，得到胶层应力的半解析理论解，并利用遗传算法对补片铺层与挖补阶梯长度进行多参数优化。结果表明：CRPOP程序可以实现阶梯修复结构的单参与多参优化，分别将胶层最大剪应力降低了28.3%和30.8%，将结构承载力提升了20.4%和25.2%。程序能够有效缓解胶层应力集中现象，并使结构获得更好的修复效果。

摘要：基于供体-受体(D-A)结构的共轭聚合物在有机光伏/光催化领域引起了广泛关注.筛选优异D、A单元进行搭配对开发性能优异的D-A结构共轭聚合物尤为重要.苯并二噻吩(BDT)稠环供体单元是目前设计最为成功的D单元之一,设计开发新型功能化的BDT单元对推进高效率D-A结构共轭聚合物的开发具有重要意义.本文以苯并[1,2-b:4,5-b′]二噻吩-4,8-二酮为原料,先后经过羰基还原、质子转换和Bouveault醛化三步合成反应,制备得到了2、5位醛基功能化的稠环D单元材料Methoxy-BDT-CHO,通过1H NMR表明了反应中间体及目标产物的正确合成.该工作为高效率D-A结构共轭聚合物的构筑提供了良好D单元.

摘要：Antibody-directed enzyme prodrug therapy（ADEPT） is a new strategy for the treatment of cancer that has arisen in recent twenty years, the main merits of which are that it can improve the selectivity of anticancer drugs and reduce the side effects in remote tissue. In the present study, two prodrugs-glycosylated aromatic nitrogen mustard derivatives were synthesized. Glucose and lactose were converted into glycosyl donors-trichloroacetimidate; the obtained glycosyl donors were glycosylated with p-nitrophenol （ glycosyl donors） to form β-glucosyl p-nitrobenzene and β-lactosyl p-nitrobenzene that were protected by acetyl in a stereoselective manner; the two products were reduced by zinc dust and then treated with ethylene oxide, afforded two glycosylated nitrogen mustard derivatives that were protected by acetyl; the last step was to deacetylate and then afforded the two target compounds that could be used as prodrugs of ADEPT for further Anti-tumor research.

摘要：Based on the antiplatelet aggregation mechanism and the bioisosterism principle of the reference drug picotamide, thirteen novel derivatives of arylamide and arylsulfonamide were designed and prepared. The biological activities of these derivatives were investigated. The chemical structures of the target compounds were confirmed by ^1H NMR and IR. The in vitro activities of antiplatelet aggregation of the thirteen target compounds were assessed by Bore＇s method. Compounds 2b and 8h have significant antiplatelet aggregation activities, which are superior to the corresponding activity of Picotamide.

摘要：A wearable and high-precision sensor for sound signal acquisition and recognition was fabricated from thin films of specially designed graphene woven fabrics （GWFs）. Upon being stretched, a high density of random cracks appears in the network, which decreases the current pathways, thereby increasing the resistance. Therefore, the film could act as a strain sensor on the human throat in order to measure one＇s speech through muscle movement, regardless of whether or not a sound is produced. The ultra-high sensitivity allows for the realization of rapid and low-frequency speech sampling by extracting the signature characteristics of sound waves. In this study, representative signals of 26 English letters, typical Chinese characters and tones, and even phrases and sentences were tested, revealing obvious and characteristic changes in resistance. Furthermore, resistance changes of the graphene sensor responded perfectly with pre-recorded sounds. By combining artificial intelligence with digital signal processing, we expect that, in the future, this graphene sensor will be able to successfully negotiate complex acoustic systems and large quantities of audio data.

摘要：研究毛蕊花糖苷(verbascoside,OC1)促进阿尔茨海默病(Alzheimer's disease,AD)发病过程中乙酰胆碱(acetylcholine,ACh)释放的分子机制。使用β-淀粉样蛋白(1~42)(Aβ_(1-42))诱导的大鼠肾上腺嗜铬细胞瘤细胞(PC12)作为AD体外模型,分为对照组(control),模型组(model,Aβ_(1-42)10μmol·L^(-1)),OC1处理组(2、10μg·mL^(-1))。通过全蛋白磷酸化修饰定量组学分析OC1对AD细胞模型磷酸化蛋白的影响,结合计算机辅助药物设计虚拟筛选OC1对于钙通道亚型的选择性,荧光探针Fluo-3/AM检测细胞中Ca^(2+)浓度,Western blot检测OC1对磷酸化钙调素依赖性蛋白激酶Ⅱ(p-CaMKⅡ,Thr286)及突触囊泡相关蛋白表达的影响,UPLC/Q Exactive MS检测OC1对AD细胞模型ACh释放的影响,试剂盒检测OC1对AD细胞模型中乙酰胆碱酯酶(acetylcholine esterase,AChE)活力的影响。结果显示,模型组与OC1处理组的差异修饰蛋白在GO分类、KEGG通路和蛋白结构域3个层面均与钙通道激活相关。分子对接结果揭示了L-型钙通道的主导作用。在Ca^(2+)螯合剂EGTA(乙二醇四乙酸)、L-型钙通道阻断剂维拉帕米(verapamil)和N-型钙通道阻断剂芋螺毒素(conotoxin)存在的条件下,OC1对Fluo-3/AM荧光强度的增强作用被削弱,且verapamil的作用强于conotoxin。这证实OC1主要通过与L-型钙通道蛋白相互作用促进细胞外Ca^(2+)内流。蛋白质组学分析和Western blot结果表明,OC1处理后p-CaMKⅡ及下游囊泡相关蛋白表达上调,说明OC1通过激活CaMKⅡ作用于囊泡相关蛋白,参与神经突触的重塑和递质释放,从而影响学习记忆。此外,OC1还降低了AChE活力,延长ACh在突触间隙的作用时间。

摘要：Changes in requirements may result in the increasing of product development project cost and lead time, therefore, it is important to understand how require- ment changes propagate in the design of complex product systems and be able to select best options to guide design. Currently, a most approach for design change is lack of take the multi-disciplinary coupling relationships and the number of parameters into account integrally. A new design change model is presented to systematically analyze and search change propagation paths. Firstly, a PDS-Be- havior-Structure-based design change model is established to describe requirement changes causing the design change propagation in behavior and structure domains. Secondly, a multi-disciplinary oriented behavior matrix is utilized to support change propagation analysis of complex product systems, and the interaction relationships of the matrix elements are used to obtain an initial set of change paths. Finally, a rough set-based propagation space reducing tool is developed to assist in narrowing change propagation paths by computing the importance of the design change parameters. The proposed new design change model and its associated tools have been demonstrated by the scheduling change propagation paths of high speed train＇s bogie to show its feasibility and effectiveness. This model is not only supportive to response quickly to diversified market requirements, but also helpful to satisfy customer require- ments and reduce product development lead time. The proposed new design change model can be applied in a wide range of engineering systems design with improved efficiency.

摘要：Herein,we report a geometrically well-defined prism assembled by two floxuridine(F)integrated RNA strands as a precise nanomedicine for chemodrug *** to the similarity between chemotherapeutic F and uridine(U),all uridines in the component RNA strands are replaced by F during their in vitro transcription *** specifically designing their sequences,F-containing S-shape tiles with the single-stranded loops are constructed and then further assemble into the RNA prism through T-junction interactions and sticky-end *** present study demonstrates that the F-integrated RNA prism can serve as an efficient platform for chemodrug delivery and anticancer *** believe that the study would help the future development of RNA-based nanomedicine in various applications.

摘要：A systemic investigation was done on the chemistry and crystal structure of boundary phases in sintered Ce9Nd21FebalB1 （wt%） magnets. Ce2Fe14B is believed to be more soluble in the rare-earth （RE）-rich liquid phase during the sintering process. Thus, the grain size and oxygen content were controlled via low-temperature sintering, resulting in high coercivity and maximum energy products. In addition, Ce formed massive agglomerations at the triple-point junctions, as confirmed by elemental mapping results. Transmission electron micros- copy （TEM） images indicated the presence of （Ce,Nd）Ox phases at grain boundaries. By controlling the composition and optimizing the preparation process, we successfully obtained Ce9Nd21FebalBx sintered magnets; the prepared magnets exhibited a residual induction, coerciv- ity, and energy product of 1.353 T, 759 kA/m, and 342 kJ/m3, respectively.