摘要：Rational protein design is a powerful strategy,not only for revealing the structure and function relationship of natural metalloproteins,but also for creating artificial metalloproteins with improved properties and ***(Mb),a small heme protein created by nature with diverse functions,has been shown to be an ideal scaffold for rational protein *** progress reviewed herein includes fine-tuning its native functions of O2binding and transport,peroxidase activity and nitrite reductase(NIR)activity,and rational expanding its functionalities to peroxygenase,heme-copper oxidase(HCO),nitric oxide reductase(NOR),as well as hydroxylamine *** studies have enhanced our understanding of how metalloproteins work in nature,and provided insights for rational design of functional metalloproteins for practical applications in the future.

摘要：The ability to finely control the structure of protein folds is an important prerequisite to functional protein design. The TIM barrelfold is an important target for these efforts as it is highly enriched for diverse functions in nature. Although a TIM barrel proteinhas been designed de novo, the ability to finely alter the curvature of the central beta barrel and the overall architecture of the foldremains elusive, limiting its utility for functional design. Here, we report the de novo design of a TIM barrel with ovoid (twofold)symmetry, drawing inspiration from natural beta and TIM barrels with ovoid curvature. We use an autoregressive backbonesampling strategy to implement our hypothesis for elongated barrel curvature, followed by an iterative enrichment sequencedesign protocol to obtain sequences which yield a high proportion of successfully folding designs. Designed sequences arehighly stable and fold to the designed barrel curvature as determined by a 2.1Å resolution crystal structure. The designs showrobustness to drastic mutations, retaining high melting temperatures even when multiple charged residues are buried in thehydrophobic core or when the hydrophobic core is ablated to alanine. As a scaffold with a greater capacity for hosting diversehydrogen bonding networks and installation of binding pockets or active sites, the ovoid TIM barrel represents a major steptowards the de novo design of functional TIM barrels.

摘要：Since the start of the Precision Medicine Initiative by the United States of America in 2015,interest in personalized medicine has grown *** short,personalized medicine is a term that describes medical treatment that is tuned to the *** possible way to realize personalized medicine is 3D *** using materials that can be tuned upon stimulation,4D printing is *** recent years,many studies have been exploring a new field that combines 3D and 4D printing with *** has resulted in many concepts of pharmaceutical devices and formulations that can be printed and,possibly,tailored to an ***,the first 3D printed drug,Spritam®,has already found its way to the *** review gives an overview of various 3D and 4D printing techniques and their applications in the pharmaceutical field as drug delivery systems and personalized medicine.

摘要：层次自己组装是在自然的一个基本原则，它产生是为在纳米技术的创新材料的开发的灵感的令人震惊的超分子的体系结构。这里，我们在场锥形的 amphiphilic 设计者肽的唯一的结构。当追踪它的集中依赖者形态学时，我们在集会过程的开始观察了伸长的 bilayered 单身者磁带，它进一步在高集中发展成新奇 double-helix-like 上层建筑。这体系结构被二单个 helices 的紧密的 intertwisting 描绘，导致在他们几百纳米的全部的长度上的一种周期的沥青尺寸。解决方案 X 光检查散布数据揭示了显著 2-layered 内部组织。所有这些特征为几乎三个月的调查时期仍然保持未改变。在他们的集体形态学，集会集成于有 hydrogel 特征的一个网络。如此的基于肽的结构为下一代的 nanostructured biomaterials 作为一块积木保持诺言。

摘要：The proposed phantom is designed for the quality control of micro-SPECT/CT and micro-PET/CT systems. However, it is an assembly of six patterns stored in a cylindrical box enabling to control both micro-SPECT unit in terms of uniformity, spatial linearity and spatial resolution and micro-CT unit in terms of uniformity, spatial linearity, spatial resolution, diffusion rate, low contrast detectability, Hounsfield unit linearity and slice thickness. The construction material is Plexiglas. As for the implementation, it was made on a micro-SPECT/CT machine of the type “speCZT eXplore CT 120”. Compared to the NEMA NU 4-2008 image quality phantom, this phantom offers micro-CT quality control and is more efficient in control of spatial resolution for micro-SPECT and micro- PET systems.

摘要：生物再生生命保障系统(BLSS)是建立月球/火星基地,实现中长期载人空间飞行必须解决的关键技术。利用高等植物或微藻来生产食物、处理废物、再生O2和水是BLSS区别于其他类型生保系统的重要标志。BLSS在结构和功能上可以分为自养单元和异养单元两部分。本文简单绘制了三种不同的系统构型。在实际选择时,应根据任务需求选择系统综合质量最小的构型而不是单纯追求高封闭度。系统设计过程应遵循物质平衡的基本原则,尤其是与航天员生命息息相关的O2平衡和水平衡。

摘要：This paper proposes an additive nanomanufacturing approach to fabricate a personalized lab-on-a-chip fluorescent peptide nanoparticles (f-PNPs) array for simultaneous multi-biomarker detection that can be used in Alzheimer’s disease (AD) diagnosis. We will discuss optimization techniques for the additive nanomanufacturing process in terms of reliability, yield and manufacturing efficiency. One contribution of this paper lies in utilization of additive nanomanufacturing techniques to fabricate a patient-specific customize-designed lab-on-a-chip device for personalized AD diagnosis, which remains a major challenge for biomedical engineering. Through the integrated bio-design and bio-manufacturing process, doctor’s check-up and computer-aided customized design are integrated into the lab-on-a-chip array for patient-specific AD diagnosis. In addition, f-PNPs with targeting moieties for personalized AD biomarkers will be self-assembled onto the customized lab-on-a-chip through the additive nanomanufacturing process, which has not been done before. Another contribution of this research is the personalized lab-on-a-chip f-PNPs array for AD diagnosis utilizing limited human blood. Blood-based AD assessment has been described as “the holy grail” of early AD detection. This research created the computer-aided design, fabrication through additive nanomanufacturing, and validation of the f-PNPs array for AD diagnosis. This is a highly interdisciplinary research contributing to nanotechnology, biomaterials, and biomedical engineering for neurodegenerative disease. The conceptual work is preliminary with intent to introduce novel techniques to the application. Large-scale manufacturing based on the proposed framework requires extensive validation and optimization.

摘要：DNA纳米技术是一种自下而上的分子自组装模式,由分子构造为起点基于核酸分子的物理和化学性质自发地形成稳定结构,遵循严格的核酸碱基配对原则,使得DNA被用作构建结构的材料基元而不是在活细胞中那样作为遗传信息的载体.通过合理地设计碱基链来达成精密控制的纳米级复杂结构的目的,研究人员在这个领域已经建立起诸多二维、三维的复杂纳米结构以及各种具有不同功能的分子机器,比如DNA计算机.本文总结了近年来DNA纳米自组装方面取得的最新进展,同时介绍DNA纳米自组装的几种不同组装方法,并对其相关应用进行了展望.

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。