Moderate- and Low-Dose of Atorvastatin Alleviate Cognition Impairment Induced by High-Fat Diet via Sirt1 Activation

Neurochemical Research - Mounting evidences have demonstrated that diet-induced obesity is associated with cognition impairment via increasing oxidative stress and inflammation in the brain....     

Molecular Modelling reveals the inhibition mechanism and structure–activity relationship of curcumin and its analogues to Staphylococcal aureus Sortase A

Previous studies found that the activity of Sortase A, a bacterial surface protein from Staphylococcus aureus, was inhibited by curcumin and its analogues. To explore this inhibitory mechanism, Sortase A and its inhibitors in complex systems were studied by molecular docking, molecular modelling, binding energy decomposition calculation and steered molecular dynamics simulations. Energy decomposition analysis indicated that PRO-163, LEU-169, GLN-172, ILE-182 and ILE-199 are key residues in Sortase A-inhibitor complexes. Furthermore, interactions between the methoxyl group on the benzene ring in the conjugated molecule (curcumin, demethoxycurcumin, bisdemethoxycurcumin) and VAL-168, LEU-169 and GLN-172 induce the inhibitory activity based on the energy decomposition and distance analyses between the whole residues and inhibitors. However, because of its coiled structure, the non-conjugated molecule, tetrahydrocurcumin, with key residues in the binding sites of Sortase A, interacted weakly with SrtA, leading to the loss of inhibitory activity. Based on these results, the methoxyl group on the benzene ring in the conjugated molecule largely influenced the inhibitory activity of the Sortase A inhibitors.     

灰茶尺蠖成虫触角及幼虫头部感器超微结构

【目的】明确灰茶尺蠖Ectropis grisescens成虫触角及幼虫头部感器的种类、形态、数量和分布,以探讨灰茶尺蠖的行为机制。【方法】利用扫描电镜技术观察灰茶尺蠖雌、雄成虫触角和5龄幼虫头部感器的超微结构。【结果】灰茶尺蠖成虫触角上分布有8种感器,分别是栓锥形感器、耳形感器、毛形感器(Ⅰ-Ⅳ)、B?hm氏鬃毛、腔锥形感器(Ⅰ和Ⅱ)、鳞形感器、锥形感器(Ⅰ和Ⅱ)和刺形感器。其中,栓锥形感器仅分布在雌蛾触角上,耳形感器、毛形感器(STⅠ-Ⅲ)仅分布在雄虫触角上。5龄幼虫触角上着生1个栓锥形感器、1个锥形感器和2个刺形感器;上唇着生有6对刺形感器,内唇着生有3对刺形感器和1对指形感器;上颚基部外侧着生有2个刺形感器;下颚及下颚须着生有5个刺形感器、9个锥形感器和2个栓锥形感器;下唇须着生有1个锥形感器和1个刺形感器;吐丝器前端着生有1对刺形感器。【结论】灰茶尺蠖雌、雄成虫触角感器存在性二型性,且雄虫上感器种类和数量较多,据此推测雄虫感受寄主植物或性信息素的能力较强;幼虫头部感器具有嗅觉和味觉功能,在其判断食物的种类和适应性等生态行为中发挥重要作用。     

Asymmetric dimethylarginine targets MAPK pathway to regulate insulin resistance in liver by activating inflammation factors

Insulin resistance is associated with impaired glucose uptake and altered protein kinase B (Akt) signaling. Previous studies have suggested asymmetric dimethylarginine (ADMA) and inflammation are two distinguish factors that correlate with insulin resistance (IR). How ADMA and inflammation factors interact and synchronize in the regulation of IR in liver remain to be elucidated. In this study, we systematically investigated whether ADMA is involved in IR using primary hepatocytes, if yes, by via which molecular mechanism. Our results demonstrated that ADMA inhibits insulin sensitivity in a concentration-dependent manner by activating inflammation factors tumor necrosis factor (TNF)-α, interleukin (IL)-1, and IL-6 in primary hepatocytes. Further analysis revealed that mitogen-activated protein kinase (MAPK) signaling pathway act downstream of ADMA and inflammation factors, and inhibition of MAPK pathway rescued the IR. Furthermore, metformin effects has been found which could reverse ADMA-induced IR by suppressing MAPK signaling pathway. To our knowledge, we, for the first time, unveiled the complicated regulatory network and interactions among ADMA, inflammation, and MAPK signaling pathway, which advanced current research on the development and regulation of IR in liver. This study also certainly provided novel insights on comprehensive diagonistics roles of ADMA as a potential biomarker.     

Molecular determinants for the chemical activation of the warmth-sensitive TRPV3 channel by the natural monoterpenoid carvacrol

Transient receptor potential vanilloid 3 (TRPV3), robustly expressed in the skin, is a nonselective calcium-permeable cation channel activated by warm temperature, voltage, and certain chemicals. Natural monoterpenoid carvacrol from plant oregano is a known skin sensitizer or allergen that specifically activates TRPV3 channel. However, how carvacrol activates TRPV3 mechanistically remains to be understood. Here, we describe the molecular determinants for chemical activation of TRPV3 by the agonist carvacrol. Patch clamp recordings reveal that carvacrol activates TRPV3 in a concentration-dependent manner, with an EC₅₀ of 0.2 mM, by increasing the probability of single-channel open conformation. Molecular docking of carvacrol into cryo-EM structure of TRPV3 combined with site-directed mutagenesis further identified a unique binding pocket formed by the channel S2-S3 linker important for mediating this interaction. Within the binding pocket consisting of four residues (Ile505, Leu508, Arg509, and Asp512), we report that Leu508 is the most critical residue for the activation of TRPV3 by carvacrol, but not 2-APB, a widely used nonspecific agonist and TRP channel modulator. Our findings demonstrate a direct binding of carvacrol to TRPV3 by targeting the channel S2-S3 linker that serves as a critical domain for chemical-mediated activation of TRPV3. We also propose that carvacrol can function as a molecular tool in the design of novel specific TRPV3 modulators for the further understanding of TRPV3 channel pharmacology.     

Characterizing mobile element insertions in 5675 genomes

Mobile element insertions (MEIs) are a major class of structural variants (SVs) and have been linked to many human genetic disorders, including hemophilia, neurofibromatosis, and various cancers. However, human MEI resources from large-scale genome sequencing are still lacking compared to those for SNPs and SVs. Here, we report a comprehensive map of 36 699 non-reference MEIs constructed from 5675 genomes, comprising 2998 Chinese samples (∼26.2×, NyuWa) and 2677 samples from the 1000 Genomes Project (∼7.4×, 1KGP). We discovered that LINE-1 insertions were highly enriched in centromere regions, implying the role of chromosome context in retroelement insertion. After functional annotation, we estimated that MEIs are responsible for about 9.3% of all protein-truncating events per genome. Finally, we built a companion database named HMEID for public use. This resource represents the latest and largest genomewide study on MEIs and will have broad utility for exploration of human MEI findings.     

扁玉螺中枢神经系统解剖及显微结构观察

对扁玉螺(Neverita didyma)中枢神经系统的大体解剖和显微结构进行了初步研究。结果表明,扁玉螺中枢神经系统包括一对口球神经节、一对脑神经节、一对侧神经节、一对足神经节及一个脏神经节。各神经节均由神经节被膜、胞体区及中央纤维网三部分组成。左右脑神经节之间和左右足神经节之间的联合以及脑-侧、脑-足和侧-足神经节之间的连索均较短。足神经节有明显的分区现象。     

闽江和漓江暗鳜mtDNA控制区序列差异分析

为解决暗鳜(Siniperca obscura)在分类上的争议,利用PCR和直接测序法分析了闽江和漓江13尾暗鳜mtDNA控制区的序列差异。在长度813bp的同源序列中,共发现71个变异位点,占分析位点总数的8.73%;定义了11个单倍型,其中闽江群体7个,漓江群体4个,两群体之间没有共享单倍型,且有37个鉴别位点。两群体间的核苷酸歧义度(Dxy)为5.421%±1.129%。分子方差分析(AMOVA)得出两群体间的固定指数(Fst)为0.852(P<0.001)。构建的NJ亲缘关系树中,闽江暗鳜和漓江暗鳜各自组群,明显分为两支。这些表明闽江和漓江暗鳜群体之间出现了显著的遗传分化,其分化可能与南岭山脉的隆起形成有关。