Pectic Galactan Polysaccharide-Based Gene Delivery System for Targeting Neuroinflammation

Treating neuroinflammation-related injuries and disorders through manipulation of neuroinflammation functions is being heralded as a new therapeutic strategy. In this study, a novel pectic galactan (PG) polysaccharide based gene therapy approach is developed for targeting reactive gliosis in neuroinflammation. Galectin-3 (Gal-3) is a cell protein with a high affinity to β-galactoside sugars and is highly expressed in reactive gliosis. Since PG carries galactans, it can target reactive gliosis via specific carbohydrate interaction between galactan and Gal-3 on the cell membrane, and therefore can be utilized as a carrier for delivering genes to these cells. The carrier is synthesized by modifying quaternary ammonium groups on the PG. The resulting quaternized PG (QPG) is found to form complexes with plasmid DNA with a mean diameter of 100 nm and have the characteristics required for targeted gene therapy. The complexes efficiently condense large amounts of plasmid per particle and successfully bind to Gal-3. The in vivo study shows that the complexes are biocompatible and safe for administration and can selectively transfect reactive glial cells of an induced cortical lesion. The results confirm that this PG-based delivery system is a promising platform for targeting Gal-3 overexpressing neuroinflammation cells for treating neuroinflammation-related injuries and neurodegenerative diseases.     

Steerable Microinvasive Probes for Localized Drug Delivery to Deep Tissue

Enhanced understanding of neuropathologies has created a need for more advanced tools. Current neural implants result in extensive glial scarring and are not able to highly localize drug delivery due to their size. Smaller implants reduce surgical trauma and improve spatial resolution, but such a reduction requires improvements in device design to enable accurate and chronic implantation in subcortical structures. Flexible needle steering techniques offer improved control over implant placement, but often require complex closed‐loop control for accurate implantation. This study reports the development of steerable microinvasive neural implants (S‐MINIs) constructed from borosilicate capillaries (OD = 60 µm, ID = 20 µm) that do not require closed‐loop guidance or guide tubes. S‐MINIs reduce glial scarring 3.5‐fold compared to prior implants. Bevel steered needles are utilized for open‐loop targeting of deep‐brain structures. This study demonstrates a sinusoidal relationship between implant bevel angle and the trajectory radius of curvature both in vitro and ex vivo. This relationship allows for bevel‐tipped capillaries to be steered to a target with an average error of 0.23 mm ± 0.19 without closed‐loop control. Polished microcapillaries present a new microinvasive tool for chronic, predictable targeting of pathophysiological structures without the need for closed‐loop feedback and complex imaging.     

纳米银-聚合物薄膜的制备及力电性能测试

聚合物基底上纳米银颗粒薄膜的制备工艺相对简单,成本较低,且该薄膜具有成为高敏感性压阻应力/应变传感材料的潜力。本文采用银镜制备法在聚酰亚胺(PI)和聚乙烯(PE)上合成了纳米银颗粒薄膜,系统研究了该薄膜制备工艺、结构特性、材料性能之间的关系。实验考察了材料“浸泡”时间及聚合物材料前处理等因素对材料表面吸附纳米颗粒含量的影响,研究了 “浸泡”时间对纳米银颗粒粒径大小、颗粒含量及分布的影响,并探讨了不同聚合物基体的颗粒特性对薄膜二维导电渗滤,压阻特性及拉伸性能的影响。研究表明,增加“浸泡”时间能够增加纳米银颗粒粒径大小,提高银颗粒的含量及分布均匀性；在相同的制备条件下,PI基底较PE基底对纳米银颗粒具有更加优异的吸附效果；在PI 和PE基底上的纳米银颗粒薄膜均表现出显著的压阻性能,且电阻对应变的敏感性随应变的增大及银颗粒含量的减少而显著提高。     

Quantifying the limits of CAR T-cell delivery in mice and men

CAR (Chimeric Antigen Receptor) T cells have demonstrated clinical success for the treatment of multiple lymphomas and leukaemias, but not for various solid tumours, despite promising data from murine models. Lower effective CAR T-cell delivery rates to human solid tumours compared to haematological malignancies in humans and solid tumours in mice might partially explain these divergent outcomes. We used anatomical and physiological data for human and rodent circulatory systems to calculate the typical perfusion of healthy and tumour tissues, and estimated the upper limits of immune cell delivery rates across different organs, tumour types and species. Estimated maximum delivery rates were up to 10 000-fold greater in mice than humans yet reported CAR T-cell doses are typically only 10–100-fold lower in mice, suggesting that the effective delivery rates of CAR T cells into tumours in clinical trials are far lower than in corresponding mouse models. Estimated delivery rates were found to be consistent with published positron emission tomography data. Results suggest that higher effective human doses may be needed to drive efficacy comparable to mouse solid tumour models, and that lower doses should be tested in mice. We posit that quantitation of species and organ-specific delivery and homing of engineered T cells will be key to unlocking their potential for solid tumours.     

Review on Zinc Oxide Nanoparticles: Antibacterial Activity and Toxicity Mechanism

Nano-Micro Letters - Antibacterial activity of zinc oxide nanoparticles (ZnO-NPs) has received significant interest worldwide particularly by the implementation of nanotechnology to synthesize...     

High-Resolution Chromosome Ideogram Representation of Currently Recognized Genes for Autism Spectrum Disorders

Recently, autism-related research has focused on the identification of various genes and disturbed pathways causing the genetically heterogeneous group of autism spectrum disorders (ASD). The list of autism-related genes has significantly increased due to better awareness with advances in genetic technology and expanding searchable genomic databases. We compiled a master list of known and clinically relevant autism spectrum disorder genes identified with supporting evidence from peer-reviewed medical literature sources by searching key words related to autism and genetics and from authoritative autism-related public access websites, such as the Simons Foundation Autism Research Institute autism genomic database dedicated to gene discovery and characterization. Our list consists of 792 genes arranged in alphabetical order in tabular form with gene symbols placed on high-resolution human chromosome ideograms, thereby enabling clinical and laboratory geneticists and genetic counsellors to access convenient visual images of the location and distribution of ASD genes. Meaningful correlations of the observed phenotype in patients with suspected/confirmed ASD gene(s) at the chromosome region or breakpoint band site can be made to inform diagnosis and gene-based personalized care and provide genetic counselling for families.     

数字化羊绒测色法及其在长度测量中的应用

针对光电法测试纤维长度等性质时,存在纤维的透光及反光信号与颜色高度相关的问题,采用数字化方法表征羊绒的颜色类别并精准地测量羊绒的长度。将彩色光电耦合器作为测色传感器,搭建了更适合纤维材料的测色装置;通过颜色模型在3种色空间的转换,得到3类颜色的羊绒在三维色空间的分布;基于系列实验,创建了有色羊绒的光学参数即无穷厚时的表观反射率表观反射率与测色装置计算的亮度指标之间的换算模型,并用实验证明采用测得的表观反射率可计算得到准确的须丛线密度曲线,从而可用光电法精准测量有色羊绒的长度。结果表明,该测色方法的测样面积大,代表性好,成本低,同时可用于其他纤维和纺织品的颜色测量。     

Electrical,thermal and microwave shielding properties of printable silver nanowires

Silver nanowires find use in a myriad of applications, including communication systems, sensors, medical devices and electrical equipment. Temperature-dependent electrical and thermal properties of chemically derived silver nanowires are rarely explored. In the present work, seed-mediated synthesis of silver nanowires has been carried out, and their electrical and thermal conductivity at 300 K is found to be 1.848?×?10⁷ S/m and 64.8 W/mK, respectively. A screen-printable ink of silver nanowires is formulated and printed on low-cost and widely used substrates like paper and cotton fabrics. Flexible printed electrodes could be made possible with uniform printed structures obtained in cotton fabric and paper substrate. The printed pattern exhibited sheet resistance of 0.7 Ω/sq. Screen-printed silver nanowires on paper show shielding efficiency of 99.9% in X band, which promotes them as excellent candidates in fabricating lightweight electronic devices by a one-step printing process.

Graphical abstract

     

A decentralized approach for convention emergence in multi-agent systems

The field of convention emergence studies how agents involved in repeated coordination games can reach consensus through only local interactions. The literature on this topic is vast and is motivated by human societies, mainly addressing coordination problems between human agents, such as who gets to redial after a dropped telephone call. In contrast, real-world engineering problems, such as coordination in wireless sensor networks, involve agents with limited resources and knowledge and thus pose certain restrictions on the complexity of the coordination mechanisms. Due to these restrictions, strategies proposed for human coordination may not be suitable for engineering applications and need to be further explored in the context of real-world application domains. In this article we take the role of designers of large decentralized multi-agent systems. We investigate the factors that speed up the convergence process of agents arranged in different static and dynamic topologies and under different interaction models, typical for engineering applications. We also study coordination problems both under partial observability and in the presence of faults (or noise). The main contributions of this article are that we propose an approach for emergent coordination, motivated by highly constrained devices, such as wireless nodes and swarm bots, in the absence of a central entity and perform extensive theoretical and empirical studies. Our approach is called Win-Stay Lose-probabilistic-Shift, generalizing two well-known strategies in game theory that have been applied in other domains. We demonstrate that our approach performs well in different settings under limited information and imposes minimal system requirements, due to its simplicity. Moreover, our technique outperforms state-of-the-art coordination mechanisms, guarantees full convergence in any topology and has the property that all convention states are absorbing.