Recent Advances in Carbon-Based Single-Atom Catalysts for Electrochemical Oxygen Reduction to Hydrogen Peroxide in Acidic Media.

Electrochemical oxygen reduction reaction (ORR) via the 2e- pathway in an acidic media shows great techno-economic potential for the production of hydrogen peroxide. Currently, carbon-based single-atom catalysts (C-SACs) have attracted extensive attention due to their tunable electronic structures, low cost, and sufficient stability in acidic media. This review summarizes recent advances in metal centers and their coordination environment in C-SACs for 2e--ORR. Firstly, the reaction mechanism of 2e--ORR on the active sites of C-SACs is systematically presented. Secondly, the structural regulation strategies for the active sites of 2e--ORR are further summarized, including the metal active center, its species and configurations of nitrogen coordination or heteroatom coordination, and their near functional groups or substitute groups, which would provide available and proper ideas for developing superior acidic 2e--ORR electrocatalysts of C-SACs. Finally, we propose the current challenges and future opportunities regarding the acidic 2e--ORR pathway on C-SACs, which will eventually accelerate the development of the distributed H2O2 electrosynthesis process.

MiR-3138 deteriorates the insulin resistance of HUVECs via KSR2/AMPK/GLUT4 signaling pathway.

Insulin resistance (IR) is a complex pathological condition resulting from the dysregulation of cellular response to insulin hormone in insulin-dependent cells and is recognized as a pathogenic hallmark and strong risk factor for metabolic syndrome. The present study aims to elucidate the molecular mechanism of the pathogenesis of IR. Here, we used human umbilical vein endothelial cells (HUVECs) to establish the IR cell model induced by 1 × 10-6 mmol/L insulin. After 48 h, reactive oxygen species (ROS) and glucose consumption were measured by DCFH-DA and GOD-POD methods, respectively. The results of Microarray analysis demonstrated that there were 10 differentially expressed miRNAs (DEMs) selected based on Fold change (FC) and P value in the IR cell model compared with HUVECs. The enriched gene ontology (GO) terms analysis showed that the target genes of these 10 DEMs were significantly enriched in biological process, cellular component and molecular function, and the significantly enriched Kyoto Encyclopedia of Genes or Genomes (KEGG) pathways mainly include AMPK signaling pathway and PI3K signaling pathway. Amongst all, the expression level of miR-3138 was highest in the IR cell model evaluated by qRT-PCR. Through Targetscan, KSR2 mRNA was predicted as a target of miR-3138. And mRNA and protein expression levels of miR-3138, KSR2, GLUT4, AMPK, PI3K, Akt were examined using qRT-PCR and Western blotting, respectively. The interaction between miR-3138 and KSR2 was evaluated by dual-luciferase reporter assay. Our results showed that miR-3138 significantly deteriorated the IR of HUVECs via KSR2/AMPK/GLUT4 signaling pathway.

Aldose reductase inhibitor protects mice from alcoholic steatosis by repressing saturated fatty acid biosynthesis.

Alcoholic liver injury results in morbidity and mortality worldwide, but there are currently no effective and safe therapeutics. Previously we demonstrated that aldose reductase (AR) inhibitor ameliorated alcoholic hepatic steatosis. To clarify the mechanism whereby AR inhibitor improves alcoholic hepatic steatosis, herein we investigated the effect of AR inhibitor on hepatic metabolism in mice fed a Lieber-DeCarli liquid diet with 5% ethanol. Nontargeted metabolomics showed carbohydrates and lipids were characteristic categories in ethanol diet-fed mice with or without AR inhibitor treatment, whereas AR inhibitor mainly affected carbohydrates and peptides. Ethanol-induced galactose metabolism and fatty acid biosynthesis are important for the induction of hepatic steatosis, while AR inhibitor impaired galactose metabolism without perturbing fatty acid biosynthesis. In parallel with successful treatment of steatosis, AR inhibitor suppressed ethanol-activated galactose metabolism and saturated fatty acid biosynthesis. Sorbitol in galactose metabolism and stearic acid in saturated fatty acid biosynthesis were potential biomarkers responsible for ethanol or ethanol plus AR inhibitor treatment. In vitro analysis confirmed that exogenous addition of sorbitol augmented ethanol-induced steatosis and stearic acid. These findings not only reveal metabolic patterns associated with disease and treatment, but also shed light on functional biomarkers contribute to AR inhibition therapy.

Inhibition of aldose reductase ameliorates alcoholic liver disease by activating AMPK and modulating oxidative stress and inflammatory cytokines.

Aldose reductase (AR) expression is elevated in the livers of patients with alcoholic liver diseases. However, the role of AR in the development of alcoholic liver diseases remains unclear. The aim of the present study was to determine the effect of AR inhibition on ethanol­induced hepatosteatosis in vivo and in vitro, and to identify possible underlying molecular mechanisms. Alcoholic fatty livers were induced in C57BL/6 mice by feeding the mice with Lieber­DeCarli liquid diets. The expression of AR protein was elevated in the liver tissue of C57BL/6 mice fed with an ethanol diet and in mouse AML12 liver cells exposed to ethanol. In addition to the elevation in AR, hepatic steatosis was observed in ethanol diet­fed mice, and this ethanol­induced steatosis was significantly attenuated by inhibiting AR activity with a specific inhibitor, zopolrestat. The suppressive effect of AR inhibition was associated with decreased levels of hepatic lipoperoxides, decreased protein expression of hepatic cytochrome P450 2E1 (CYP2E1), increased phosphorylation of 5'­AMP­activated protein kinase (AMPK) and decreased mRNA expression of tumor necrosis factor­α (TNF­α). Treatment with the AR inhibitor attenuated the level of lipid accumulation and oxidative stress, activated AMPK, and suppressed the mRNA expression of TNF­α, interleukin­6 and transforming growth factor­ß1 in ethanol­treated AML12 cells. The results of the present study demonstrated that inhibition of AR ameliorated alcoholic liver disease in vivo and in vitro, in part by activating AMPK, decreasing CYP2E1­mediated oxidative stress and ameliorating the expression of pro­inflammatory cytokines.