Electrochemical Quantification of Neurotransmitters in Single Live Cell Vesicles Shows Exocytosis is Predominantly Partial

Exocytosis plays an essential role in the communication between cells in the nervous system. Understanding the regulation of neurotransmitter release during exocytosis and the amount of neurotransmitter content that is stored in vesicles is of importance, as it provides fundamental insights to understand how the brain works and how neurons elicit a certain behavior. In this minireview, we summarize recent progress in amperometric measurements for monitoring exocytosis in single cells and electrochemical cytometry measurements of vesicular neurotransmitter content in individual vesicles. Important steps have increased our understanding of the different mechanisms of exocytosis. Increasing evidence is firmly establishing that partial release is the primary mechanism of release in multiple cell types.     

Aminoacyl-tRNA Synthetases as Valuable Targets for Antimicrobial Drug Discovery

Aminoacyl-tRNA synthetases (aaRSs) catalyze the esterification of tRNA with a cognate amino acid and are essential enzymes in all three kingdoms of life. Due to their important role in the translation of the genetic code, aaRSs have been recognized as suitable targets for the development of small molecule anti-infectives. In this review, following a concise discussion of aaRS catalytic and proof-reading activities, the various inhibitory mechanisms of reported natural and synthetic aaRS inhibitors are discussed. Using the expanding repository of ligand-bound X-ray crystal structures, we classified these compounds based on their binding sites, focusing on their ability to compete with the association of one, or more of the canonical aaRS substrates. In parallel, we examined the determinants of species-selectivity and discuss potential resistance mechanisms of some of the inhibitor classes. Combined, this structural perspective highlights the opportunities for further exploration of the aaRS enzyme family as antimicrobial targets.     

纳米药物非临床药代动力学的研究策略及关注要点

随着纳米技术的迅速发展，纳米药物的研发已成为目前药物创新的发展方向之一。纳米药物具有基于纳米结构的尺度效应，其药代动力学特征与普通药物相比存在明显差异，其药代动力学研究与普通药物相比也有其特殊性。本文着重探讨纳米药物的非临床药代动力学的研究策略及关注要点，包括受试物、体内/外试验、生物样本分析、数据评价分析等，期望为研发者提供参考。     

Phenotypic Discovery of SB1501, an Anti-obesity Agent,through Modulating Mitochondrial Activity

Obesity has become a pandemic that threatens the quality of life and discovering novel therapeutic agents that can reverse obesity and obesity-related metabolic disorders are necessary. Here, we aimed to identify new anti-obesity agents using a phenotype-based approach. We performed image-based high-content screening with a fluorogenic bioprobe (SF44), which visualizes cellular lipid droplets (LDs), to identify initial hit compounds. A structure-activity relationship study led us to yield a bioactive compound SB1501, which reduces cellular LDs in 3T3-L1 adipocytes without cytotoxicity. SB1501 induced the expression of gene products that regulate mitochondrial biogenesis and fatty acid oxidation in 3T3-L1 adipocytes. Daily treatment with SB1501 improved the metabolic states of db/db mice by reducing body fat mass, adipose tissue mass, food intake, and increasing glucose tolerance. The anti-obesity effect of SB1501 may result from perturbation of the PGC-1α–UCP1 regulatory axis in inguinal white adipose tissue and brown adipose tissue. These data suggest the therapeutic potential of SB1501 as an anti-obesity agent via modulating mitochondrial activities.     

Life time prediction of self-supporting flame-sprayed alumina-rich coatings

Main objective of the presented research is the life time prediction of self-supporting flame-sprayed Al₂O₃- and Al₂O₃ -ZrO₂ -TiO₂-materials under constant load. The characteristic life time and its scatter were derived from stable crack growth tests and Weibull-statistics including the four-point-bending and ball-on-three-balls method. The potential life time was estimated in order to assess room-temperature handling and long term storage of self-supporting flame-sprayed alumina components. In terms of flexural strength, energy release, and subcritical crack growth parameters, distinct differences between both materials were shown. In turn, the characteristic life times only barely deviated from each other. From that the conclusion was drawn that life time performance under constant load application is governed by the characteristic flame-spray microstructure. However, advantages in the flame-spray processing of Al₂O₃ - ZrO₂ -TiO₂ are still given, attributed to its lower melting temperature.     

公众食品药品网络谣言和虚假宣传辨识能力调查——以贵州省某少数民族自治地区为例

目的 了解公众对网络食品药品谣言信息及虚假宣传甄别能力和行为态度，探索防范谣言传播、维护社会稳定的有效措施和途径。方法 采用随机抽样研究方法，对贵州省某少数民族自治州公众开展食品药品网络谣言及虚假宣传辨识能力、行为态度问卷调查。结果 当地公众食品药品网络谣言及虚假宣传辨识能力总体较低，经济发展落后地区的青少年人群对网络谣言及虚假宣传的辨识能力较弱。大部分公众处理网络食品药品安全信息较为理性，更愿意通过国家监管部门权威网站了解信息，基本具备了确认信息真实性的主观意识，但辟除谣言的行动能力不高。结论 地方党委政府及有关部门应加强食品药品网络谣言和虚假宣传治理，加大当地谣言及虚假宣传的监测和系统性分析研究，有针对性、预判性地进行治理和科普宣传。     

Dual pH‐ and thermal‐responsive nanocomposite hydrogels for controllable delivery of hydrophobic drug baicalein

Hydrogels have been widely used as mild biomaterials due to their bio‐affinity, high drug loading capability and controllable release profiles. However, hydrogel‐based carriers are greatly limited for the delivery of hydrophobic payloads due to the lack of hydrophobic binding sites. Herein, nano‐liposome micelles were embedded in semi‐interpenetrating poly[(N‐isopropylacrylamide)‐co‐chitosan] (PNIPAAm‐co‐CS) and poly[(N‐isopropylacrylamide)‐co‐(sodium alginate)] (PNIPAAm‐co‐SA) hydrogels which were responsive to both temperature and pH, thereby establishing tunable nanocomposite hydrogel delivery systems. Nano‐micelles formed via the self‐assembly of phospholipid could serve as the link between hydrophobic drug and hydrophilic hydrogel due to their special amphiphilic structure. The results of transmission and scanning electron microscopies and infrared spectroscopy showed that the porous hydrogels were successfully fabricated and the liposomes encapsulated with baicalein could be well contained in the network. In addition, the experimental results of response release in vitro revealed that the smart hydrogels showed different degree of sensitiveness under different pH and temperature stimuli. The results of the study demonstrate that combining PNIPAAm‐co‐SA and PNIPAAm‐co‐CS hydrogels with liposomes encapsulated with hydrophobic drugs is a feasible method for hydrophobic drug delivery and have potential application prospects in the medical field. © 2018 Society of Chemical Industry     

贵州北盘江增殖放流效果评价

为了评估北盘江鱼类增殖放流效果,2017~2018年期间采用体外荧光、剪鳍、"T"型标三种标志方法对目标鱼类进行标志放流,通过集中捕捞方式进行回捕调查,集中捕捞时间为2017年7月、2018年8月,捕捞水域为董菁-马马崖-光照-善泥坡库区。结果表明,白甲鱼回捕率较高,为0.82%,其他鱼类均在0.5%左右,其中主要为低龄鱼类,高龄鱼类较少;董菁打邦河及各库尾水域物种丰富度较高,善泥坡高家渡码头和马马崖库区试验库尾物种多样性指数相对较低。建议在以后的增殖放流活动中,加大每年的监测频次。