0 mAh cm-2 . This work offers an important pathway toward solid-state polymer electrolytes for high-voltage solid-state batteries. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Alcoholic liver disease is the most prevalent chronic liver disease. Melatonin is known to control many vital processes. Here, we explored a novel molecular mechanism by which melatonin-induced SIRT1 signaling protects against alcohol-mediated oxidative stress and liver injury. STA-9090 clinical trial Gene expression profiles and metabolic changes were measured in liver specimens of mice and human subjects. Expression levels of Cb1r, Crbn, Btg2, Yy1, pro-inflammatory cytokines, and Cyp2e1 were significantly enhanced in chronic alcohol-challenged mice and human subjects. Levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic CYP2E1 protein, and reactive oxygen species (ROS) were elevated in alcohol-fed WT mice but not in Cb1r antagonist-treated, Crbn null, or Yy1-silenced mice. Importantly, alcohol-induced Yy1 and Cyp2e1 expression, ROS amount, and liver injury were markedly diminished by melatonin treatment and the transduction of Sirt1 in mice, whereas this phenomenon was prominently ablated by silencing of Sirt1. Notably, SIRT1 physically interacted with YY1 and attenuated YY1 occupancy on the Cyp2e1 gene promoter. Melatonin-SIRT1 signaling ameliorates alcohol-induced oxidative liver injury by disrupting the CRBN-YY1-CYP2E1 signaling pathway. The manipulation of CRBN-YY1-CYP2E1 signaling network by the melatonin-SIRT1 pathway highlights a novel entry point for treating alcoholic liver disease. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.Computational models of plants have identified gaps in our understanding of biological systems, and have revealed ways to optimize cellular processes or organ-level architecture to increase productivity. Thus, computational models are learning tools that help direct experimentation and measurements. Models are simplifications of complex systems, and often simulate specific processes at single scales (e.g., temporal, spatial, organizational, etc.). Consequently, single-scale models are unable to capture the critical cross-scale interactions that result in emergent properties of the system. In this perspective article, we contend that to accurately predict how a plant will respond in an untested environment, it is necessary to integrate mathematical models across biological scales. Computationally mimicking the flow of biological information from the genome to the phenome is an important step in discovering new experimental strategies to improve crops. A key challenge is to connect models across biological, temporal, and computational (e.g. CPU vs GPU) scales, and then to visualize and interpret integrated model outputs. We address this challenge by describing the efforts of the international Crops in silico consortium. This article is protected by copyright. All rights reserved.Monocytic-lineage cells in the central nervous system (CNS), including microglia and brain resident macrophages, are the key players in the CNS innate immunity against viral infections, including human immunodeficiency virus (HIV). However, these cells also serve as the major targets and reservoirs for HIV in the CNS. To address the question of how HIV can establish persistent infection in the target cells in the CNS, we examined whether HIV has the ability to counteract Toll-like receptor 3 (TLR3) activation-mediated antiviral immunity in microglia and macrophages. We observed that HIV latently infected microglial cells (HC69.5) expressed reduced levels of TLR3 and TLR3 activation-mediated interferons (IFN-α/β and IFN-λ) as compared with the uninfected control cells (C20). In addition, HIV infection of primary human macrophages suppressed the expression of TLR3 and the IFNs. HIV infection also inhibited the expression of the antiviral ISGs and the HIV-restriction miRNAs. Mechanistically, HIV infection inhibited the phosphorylation of IFN regulatory factors (IRF3 and IRF7) and signal transducer and activator of transcription proteins (STAT1 and STAT3) in both HIV latently infected microglia and acutely infected macrophages. These findings provide previously unrecognized and sound mechanisms for HIV infection and persistence in the primary target and reservoir cells in the brain. This article is protected by copyright. All rights reserved.Both subsets of MCs including MCTC (tryptase-positive, chymase-positive) and MCT (tryptase-positive, chymase-negative) are present in the testis and epididymis. Increased number of MCs, higher levels of MC-released tryptase in testis and seminal plasma of males with fertility problems, and promoting sperm motility in individuals with oligozoospermia after using MC blockers provide evidence that MCs may play a role in male infertility/subfertility disturbances. MC-released tryptase and histamine contribute to the fibrosis and may disrupt spermatogenesis. MCs not only influence the process of spermatogenesis but also have effects on the function of other testis-residing cells. MC-derived histamine may influence the steroidogenesis of Leydig cells by acting through H1R and H2R receptors. Additionally, the interaction between MC-released ATP and P2X receptors expressed on the peritubular cells may induce the production of the pro-inflammatory mediators by peritubular cells. Further investigations showed that MCs ve a role in abortion by releasing TNF-α. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.Transposable elements (TEs) are sequences currently or historically mobile, and are present across all eukaryotic genomes. A growing interest in understanding the regulation and function of TEs has revealed seemingly dichotomous roles for these elements in evolution, development, and disease. On the one hand, many gene regulatory networks owe their organization to the spread of cis-elements and DNA binding sites through TE mobilization during evolution. On the other hand, the uncontrolled activity of transposons can generate mutations and contribute to disease, including cancer, while their increased expression may also trigger immune pathways that result in inflammation or senescence. Interestingly, TEs have recently been found to have novel essential functions during mammalian development. Here, the function and regulation of TEs are discussed, with a focus on LINE1 in mammals. It is proposed that LINE1 is a beneficial endogenous dual regulator of gene expression and genomic diversity during mammalian development, and that both of these functions may be detrimental if deregulated in disease contexts.