Plasma membranes of animal cells are enriched for cholesterol. Cholesterol-dependent cytolysins (CDCs) are pore forming toxins secreted by bacteria that target membrane cholesterol for their effector function. Phagocytes are essential for clearance of CDC-producing bacteria; however, mechanisms these cells use to evade the deleterious effects of CDCs are largely unknown. Here, we report that interferon (IFN) signals convey resistance to CDC-induced pores on macrophages Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms

Immune cells are vital constituents of the adipose microenvironment that influence both local and systemic lipid metabolism. Mice lacking IL10 have enhanced thermogenesis, but the roles of specific cell types in the metabolic response to IL10 remain to be defined. We demonstrate here that selective loss of IL10 receptor α in adipocytes recapitulates the beneficial effects of global IL10 deletion, and that local crosstalk between IL10-producing immune cells and adipocytes is a determinant of thermogenesis and systemic energy balance. Single Nuclei Adipocyte RNA-sequencing (SNAP-seq) of subcutaneous adipose tissue defined a metabolically-active mature adipocyte subtype characterized by robust expression of genes involved in thermogenesis whose transcriptome was selectively responsive to IL10Rα deletion. Furthermore, single-cell transcriptomic analysis of adipose stromal populations identified lymphocytes as a key source of IL10 production in response to thermogenic stimuli. These findings implicate adaptive immune cell-adipocyte communication in the maintenance of adipose subtype identity and function.

Delivery to the proper tissue compartment is a major obstacle hampering the potential of cellular therapeutics for medical conditions. Delivery of cells within biomaterials may improve localization, but traditional and newer void‐forming hydrogels must be made in advance with cells being added into the scaffold during the manufacturing process. Injectable, in situ cross‐linking microporous scaffolds are recently developed that demonstrate a remarkable ability to provide a matrix for cellular proliferation and growth in vitro in three dimensions. The ability of these scaffolds to deliver cells in vivo is currently unknown. Herein, it is shown that mesenchymal stem cells (MSCs) can be co‐injected locally with microparticle scaffolds assembled in situ immediately following injection. MSC delivery within a microporous scaffold enhances MSC retention subcutaneously when compared to cell delivery alone or delivery within traditional in situ cross‐linked nanoporous hydrogels. After two weeks, endothelial cells forming blood vessels are recruited to the scaffold and cells retaining the MSC marker CD29 remain viable within the scaffold. These findings highlight the utility of this approach in achieving localized delivery of stem cells through an injectable porous matrix while limiting obstacles of introducing cells within the scaffold manufacturing process.

Immune cells are vital constituents of the adipose microenvironment that influence both local and systemic lipid metabolism. Mice lacking IL10 have enhanced thermogenesis, but the roles of specific cell types in the metabolic response to IL10 remain to be defined. We demonstrate here that selective loss of IL10 receptor a in adipocytes recapitulates the beneficial effects of global IL10 deletion, and that local crosstalk between IL10-producing immune cells and adipocytes is a determinant of thermogenesis and systemic energy balance. Single Nuclei Adipocyte RNA-sequencing (SNAP-seq) of subcutaneous adipose tissue defined a metabolically-active mature adipocyte subtype characterized by robust expression of genes involved in thermogenesis whose transcriptome was selectively responsive to IL10Ra deletion.Furthermore, single-cell transcriptomic analysis of adipose stromal populations identified lymphocytes as a key source of IL10 production in response to thermogenic stimuli. These findings implicate adaptive immune cell-adipocyte communication in the maintenance of adipose subtype identity and function.3

Liver transplantation is performed in the recent decades with great improvements not only technically but also conceptually. However, there is still lack of consensus about the optimal hemodynamic characteristics during liver transplantation. The representative hemodynamic parameters include portal vein pressure, portal vein flow, and hepatic venous pressure gradient; however, there are still others potential valuable parameters, such as total liver inflow and hepatic artery flow. All the parameters are correlated closely and some internal modulating mechanisms, like hepatic arterial buffer response, occur to maintain stable hepatic inflow. To distinguish the unique importance of each hepatic and systemic parameter in different states during liver transplantation, we reviewed the published data and also conducted two transplant cases with different surgical strategies applied to achieve ideal portal inflow and pressure.

NCs post- liver transplantation occurs because of factors related to recipient, donor, and surgeon. Our results provide a basis of risk stratification for surgeon to minimize neurotoxic factors during transplantation.

Hepatitis C virus (HCV) infection is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). HCV core protein is considered as a positive regulator of telomerase activity. In this study, we focused on the deregulated microRNA-138 (miR-138) in HCV-associated HCC. Differential expression of miR-138 was determined by TaqMan quantitative real-time PCR. The target gene of miR-138 was verified by luciferase reporter assay, quantitative real-time PCR, and Western blotting. Moreover, three assays based on telomerase activity, cell proliferation, and senescence-associated β-galactosidase activity were performed. The correlation analysis revealed a significantly negative correlation between miR-138 and telomerase reverse transcriptase (TERT) mRNA expression in HCC. Further, we showed that mature HCV core protein of 173 amino acids, but not full-length form of 191 amino acids, suppressed miR-138 expression. TERT was verified as a direct target of miR-138 in HCC cells. Furthermore, TERT-targeting miR-138 supplementation can prevent HCV core protein from repressing HCC cell replicative senescence. Collectively, HCV core protein can enhance TERT protein expression through downregulating TERT-targeting miR-138 expression, which in turn inhibits HCC cell replicative senescence. This study may further help our understanding on the pathogenic mechanisms of HCV core protein in HCV-associated HCC development. KEY MESSAGE: miR-138 is downregulated in HCV-associated HCC. Mature HCV core protein plays a pathogenic role in suppressing miR-138 expression. Telomerase reverse transcriptase represents a direct target of miR-138 in HCC cells. miR-138 promotes HCC cell senescence, suggesting potential for HCC treatment.

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