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Adipocytokine leptin promotes hepatic stellate cell (HSC) activation (a key step in liver fibrogenesis) and liver fibrosis. microRNA-122 (miR-122) is the most abundant liver-specific miRNA and was demonstrated to inhibit liver fibrosis and reduced HSC proliferation. Our previous study revealed that leptin reduced miR-122 level in HSCs. This study was aimed to investigate whether leptin affected miR-122 promoter and the underlying mechanisms in HSCs. Results showed that leptin inhibited miR-122 promoter activity. Forkhead box protein O1(FoxO1) bound to miR-122 promoter at a site around – 56 and thus promoted miR-122 promoter activity, which could be suppressed by leptin-induced phosphorylation of FoxO1 at serine 256. The PI3K/Akt signaling pathway was involved in leptin-induced phosphorylation of FoxO1 and the effect of leptin on miR-122 expression. Furthermore, FoxO1 increased miR-122 and pri-miR-122 (primary miR-122) levels in HSCs in vivo, and reduced leptin-induced HSC activation and liver fibrosis in ob/ob mouse (leptin deficient) model. In conclusion, leptin suppressed microRNA-122 expression by PI3K/Akt/foxO1 axis in HSCs. These results have potential implications for clarifying the mechanisms for liver fibrogenesis in obese patients with hyperleptinaemia. [ABSTRACT FROM AUTHOR]

The over proliferation of harmful cyanobacteria and their cyanotoxins resulted in damaged aquatic ecosystem, polluted drinking water and threatened human health. Cyanophages are a kind of viruses that exclusively infect cyanobacteria, which is considered as a potential strategy to deal with cyanobacterial blooms. Nevertheless, the infecting host range and/or lysis efficiency of natural cyanophages is limited, rising the necessity of constructing non-natural cyanophages via artificial modification, design and synthesis to expand their host range and/or efficiency. The paper firstly reviewed representative cyanophages such as P60 with a short latent period of 1.5 h and S-CBS1 having a burst size up to 200 PFU/cell. To explore the in-silico design principles, we critically summarized the interactions between cyanophages and the hosts, indicating modifying the recognized receptors, enhancing the adsorption ability, changing the lysogeny and excluding the defense of hosts are important for artificial cyanophages. The research progress of synthesizing artificial cyanophages were summarized subsequently, raising the importance of developing genetic manipulation technologies and their rescue strategies in the future. Meanwhile, Large-scale preparation of cyanophages for bloom control is a big challenge. The application prospects of artificial cyanophages besides cyanobacteria bloom control like adaptive evolution and phage therapy were discussed at last. The review will promote the design, synthesis and application of cyanophages for cyanobacteria blooms, which may provide new insights for the related water pollution control and ensuring hydrosphere security. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: The Wood-Ljungdahl pathway is responsible for acetyl-CoA biosynthesis and used as a major mean of generating energy for growth in some anaerobic microbes. Series of genes, from the anaerobic human pathogen Clostridium difficile, have been identified that show striking similarity to the genes involved in this pathway including methyltetrahydrofolate- and corrinoid-dependent methyltransferase. This methyltransferase plays a central role in this pathway that transfers the methyl group from methyltetrahydrofolate to a cob(I)amide center in the corrinoid iron–sulfur protein. In this study, we developed two efficient expression and purification methods for methyltransferase from C. difficile for the first time with two expression vectors MBPHT-mCherry2 and pETDuet-1, respectively. Using the latter vector, more than 50mg MeTr was produced per liter Luria–Bertani broth media. The recombinant methyltransferase was well characterized by SDS–PAGE, gel filtration chromatography, enzyme assay and far-UV circular dichroism (CD). Furthermore, a highly effective approach was established for determining the methyl transfer activity of the methyltetrahydrofolate- and cobalamin-dependent methyltransferase using exogenous cobalamin as a substrate by stopped-flow method. These results will provide a solid basis for further study of the methyltransferase and the Wood-Ljungdahl pathway. [Copyright &y& Elsevier]

Obese patients, often accompanied by hyperleptinemia, are prone to liver fibrogenesis. Leptin is an adipocyte-derived hormone and plays a promotion role in liver fibrosis. Sterol regulatory element binding protein-1c (SREBP1c) exerts a crucial role in inhibiting hepatic stellate cell (HSC) activation, a key step in liver fibrogenesis. Our previous studies indicated that leptin inhibited SREBP1c expression, contributing to leptin-induced HSC activation and liver fibrosis. microRNAs (miR) have emerged as important layers of regulatory control and regulate gene expression, and are implicated in numerous diseases. The present study revealed leptin up-regulation of miR-27a/b-3p levels in HSCs in vitro and in vivo. Three signaling pathways were required for leptin regulation of miR-27a/b-3p levels. miR-27a/b-3p could reduce SREBP1c and liver x receptor α (LXRα) levels, increased α-smooth muscle actin (α-SMA, a marker for HSC activation) and α1(I)collagen levels in cultured HSCs. miR-27a/b-3p regulation of SREBP1c and LXRα were independent of 3′-untranslated region of SREBP1c and LXRα mRNA. In vivo experiments further demonstrated the miR-27a/b-3p involved in leptin-associated decrease in SREBP1 level in HSCs, HSC activation, and liver fibrosis. These data might have potential implications for our understanding of molecular mechanisms underlying leptin roles in liver fibrogenesis of obese patients with hyperleptinaemia. [ABSTRACT FROM AUTHOR]

Autoimmunity refers to the phenomenon that the body's immune system produces antibodies or sensitized lymphocytes to its own tissues to cause an immune response. Immune disorders caused by autoimmunity can mediate autoimmune diseases. Autoimmune diseases have complicated pathogenesis due to the many types of cells involved, and the mechanism is still unclear. The emergence of single-cell research technology can solve the problem that ordinary transcriptome technology cannot be accurate to cell type. It provides unbiased results through independent analysis of cells in tissues and provides more mRNA information for identifying cell subpopulations, which provides a novel approach to study disruption of immune tolerance and disturbance of pro-inflammatory pathways on a cellular basis. It may fundamentally change the understanding of molecular pathways in the pathogenesis of autoimmune diseases and develop targeted drugs. Single-cell transcriptome sequencing (scRNA-seq) has been widely applied in autoimmune diseases, which provides a powerful tool for demonstrating the cellular heterogeneity of tissues involved in various immune inflammations, identifying pathogenic cell populations, and revealing the mechanism of disease occurrence and development. This review describes the principles of scRNA-seq, introduces common sequencing platforms and practical procedures, and focuses on the progress of scRNA-seq in 41 autoimmune diseases, which include 9 systemic autoimmune diseases and autoinflammatory diseases (rheumatoid arthritis, systemic lupus erythematosus, etc.) and 32 organ-specific autoimmune diseases (5 Skin diseases, 3 Nervous system diseases, 4 Eye diseases, 2 Respiratory system diseases, 2 Circulatory system diseases, 6 Liver, Gallbladder and Pancreas diseases, 2 Gastrointestinal system diseases, 3 Muscle, Bones and joint diseases, 3 Urinary system diseases, 2 Reproductive system diseases). This review also prospects the molecular mechanism targets of autoimmune diseases from the multi-molecular level and multi-dimensional analysis combined with single-cell multi-omics sequencing technology (such as scRNA-seq, Single cell ATAC-seq and single cell immune group library sequencing), which provides a reference for further exploring the pathogenesis and marker screening of autoimmune diseases and autoimmune inflammatory diseases in the future. • This review focuses on explaining the principles of scRNA-seq, common sequencing platforms and practical operation procedures, and also focuses on the progress of scRNA-seq in 41 autoimmune diseases. • This review prospect the molecular mechanism targets of autoimmune diseases from the multi-molecular level and multi-dimensional analysis combined with single cell multi-group technology. • This review provides a reference for further exploring the pathogenesis and marker screening of autoimmune diseases and autoimmune inflammatory diseases in the future. [ABSTRACT FROM AUTHOR]

Two calixarene-based coordination chains were obtained solvothermally with a bridging ligand, 5-(4-Pyridyl)-1 H -1,2,4-triazole-3-thiol (L) upon the adding of triethylamine or concentrated HCl, namely, [(C 2 H 5) 3 NH] 2 [Co 4 (TC4A)(L) 2 (SO 4) 2 ]·5(CH 3 OH) (CIAC-256) and [Co 8 (TC4A) 2 (L) 2 (SO 4) 3 (CH 3 OH) 6 ]·2(C 3 H 7 NO)·3(CH 3 OH) (CIAC-257 ; H 4 TC4A ​= ​ p -tert-butylthiacalix [4]arene). Both compounds are featured with some 1D wavy (or zigzag) chains. In CIAC-256 , the shuttlecock-like Co 4 -TC4A secondary building units (SBUs) are interconnected by the L ligands into the chains while in CIAC-257 , the SBUs are bridged by both the L ligands and the sulfonate anions. Both compounds are effective adsorbents for the selective removal of Hg(II) from the aqueous solution and the maximum adsorption capacities for Hg(II) are 411 ​mg/g for CIAC-256 and 307 ​mg/g for CIAC-257 , respectively. Magnetic measurements suggest that all the cobalt (II) centers exhibit antiferromagnetic interactions. [Display omitted] • Two 1D calixarene-based coordination chains were synthesized at different pH values. • All the cobalt (II) centers exhibit antiferromagnetic interactions. • Both compounds are effective adsorbents for selective Hg(II) removal. [ABSTRACT FROM AUTHOR]