摘要：With numerous advancements in novel biochemical techniques, our knowledge of the role of RNAs in the regulation of cellular physiology and pathology has grown significantly over the past several decades. Nevertheless, detailed information regarding RNA processing, trafficking, and localization in living cells has been lacking due to technical limitations in imaging single RNA transcripts in living cells with high spatial and temporal resolution. In this review, we discuss tech- niques that have shown great promise for single RNA imaging, followed by highlights in our recent work in the development of molecular beacons （MBs）, a class of nanoscale oligonucleotide-probes, for detecting individual RNA transcripts in living cells. With further refinement of MB design and development of more sophisticated fluorescence microscopy techniques, we envision that MB-based approaches could promote new discoveries of RNA functions and activities.

摘要：We report a rationally designed one-pot method for the facile synthesis of Pd concave nanocubes in an aqueous solution at room temperature by manipulating the reduction kinetics through the selection of a proper combination of a salt precursor （PdBr4^2-） and reductant （sodium ascorbate）. Our kinetic analysis demonstrates that, through this selection, the nucleation and growth of Pd nanocrystals could be effectively separated into two kinetic regimes involving distinctive reduction pathways： i） solution reduction for the initial formation of single-crystal seeds and ii） surface reduction for the formation of concave nanocrystals via autocatalytic growth from the single-crystal seeds. The suppressed surface diffusion at room temperature, when coupled with the capping effect of bromide ions, ultimately leads to the formation of concave nanocubes with an asymmetric shape and high-index facets, whose synthesis would otherwise require multiple steps and the use of elevated temperatures.

摘要：CD8+T细胞主要通过T细胞表面受体(T cell recep tor,TCR)识别并与Ⅰ型主要组织性复合物提呈的抗原(pMHC-Ⅰ)相互作用[1]。TCR对刺激型抗原的识别在CD8+T细胞毒性和适应性免疫中发挥着关键作用。许多证据表明机械力可以延长TCR与刺激性pMHC作用的键合时间(bond lifetime)形成抗原特异性逆锁键(catch bond)[2],并且这种逆锁键对抗原识别非常重要。然而,机械力调控TCR抗原识别的具体结构机制仍不清楚。通过分子动力学模拟、单分子生物膜力学探针、磁镊、T细胞活化实验和动物模型对此问题展开了系统的研究[4]。发现作用在TCR-pMHC-Ⅰ复合体上的拉力可以作用在TCR-pMHC-Ⅰ复合体上的拉力可以打破MHC-I分子内部α1-α2和β2结构域间的相互作用,导致α1-α2结构域旋转并发生构象变化。力诱导的MHC-I构象变化可以进一步别构地调节TCR与刺激性抗原肽及α1-α2结构域的构象及相互作用,诱导产生新的氢键,增强TCR-pMHC-Ⅰ之间的键合时间,但并不能增强TCR与抑制性pMHC-Ⅰ之间的作用。当用点突变阻断这些新形成的氢键,或者α1-α2和β2结构域被二硫键锁住时,最佳力诱导的TCR-pMHC-Ⅰ作用的键合时间明显缩短并且T细胞的活化受到抑制。另外,在人TCR和HLA-A2相互作用中发现了类似机制,并且与肿瘤相关的HLA-A2点突变[3]可以通过限制HLA-A2α1--α2和β2结构域之间的构象打开减弱TCR对肿瘤抗原的识别及T细胞的功能。研究结果表明,机械力诱导的MHC-I构象变化对TCR抗原识别和T细胞活化非常重要,进一步地阐明了机械力调控TCR抗原识别机制,为临床肿瘤的免疫治疗和药物设计提供了新思路和新靶点。