Constructing highly efficient bifunctional catalysts for oxygen reduction and oxygen evolution by modifying MXene with transition metal.

Exploring highly active electrocatalysts for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) has become a growing interest in recent years. Herein, an efficient pathway for designing MXene-based ORR/OER catalysts is proposed. It involves introducing non-noble metals into Vo (vacancy site), H1 and H2 (the hollow sites on top of C and the metal atom, respectively) sites on M2CO2 surfaces, named TM-VO/H1/H2-M2CO2 (TM = Fe, Co, Ni, M = V, Nb, Ta). Among these recombination catalysts, Co-H1-V2CO2 and Ni-H1-V2CO2 exhibit the most promising ORR catalytic activities, with low overpotential values of 0.35 and 0.37 V, respectively. Similarly, Fe-H1-V2CO2, Co-VO-Nb2CO2, and Ni-H2-Nb2CO2 possess low OER overpotential values of 0.29, 0.39, and 0.44 V, respectively, suggesting they have enormous potential as effective catalysts for OER. Notably, Co-H2-Ta2CO2 possesses the lowest potential gap value of 0.53 V, demonstrating it has an extraordinary bifunctional catalytic activity. The excellent catalytic performance of these recombination catalysts can be elucidated through an electronic structure analysis, which primarily relies on the electron-donating capacity and synergistic effects between transition metals and sub-metals. These results provide theoretical guidance for designing new ORR and OER catalysts using 2D MXene materials.

Overexpression of miR-297b-5p in Mouse Insulin-Secreting Cells Promotes Metformin-Mediated Protection Against Stearic Acid-Induced Senescence by Targeting Igf1r.

BACKGROUND: A long-term consumption of saturated fat significantly increases the concentration of saturated fatty acids in serum, which accelerates the appearance of senescence markers in ß-cells and leads to their dysfunction. An understanding of the mechanisms underlying ß-cell senescence induced by stearic acid and the exploration of effective agents preventing it remains largely unclear. Here, we aimed to investigate the protective effect of metformin against stearic acid-treated ß-cell senescence and to assess the involvement of miR-297b-5p in this process. METHODS: To identify senescence, we measured senescence-associated ß-galactosidase activity and the expression of senescence-related genes. Gain and loss of function approaches were applied to explore the role of miR-297b-5p in stearic acid-induced ß-cell senescence. Bioinformatics analysis and a luciferase activity assay were used to predict the downstream targets of miR-297b-5p. RESULTS: Stearic acid markedly induced senescence and suppressed miR-297b-5p expression in mouse ß-TC6 cells, which were significantly alleviated by metformin. After transfection of miR-297b-5p mimics, stearic acid-evoked ß-cell senescence was remarkably prevented. Insulin-like growth factor-1 receptor was identified as a direct target of miR-297b-5p. Inhibition of the insulin-like growth factor-1 receptor prevented stearic acid-induced ß-cell senescence and dysfunction. Moreover, metformin alleviates the impairment of the miR-297b-5p inhibitor in ß-TC6 cells. Additionally, long-term consumption of a high-stearic-acid diet significantly increased senescence and reduced miR-297b-5p expression in mouse islets. CONCLUSIONS: These findings imply that metformin alleviates ß-cell senescence by stearic acid through upregulating miR-297b-5p to suppress insulin-like growth factor-1 receptor expression, thereby providing a potential target to not only prevent high fat-diet-induced ß-cell dysfunction but also for metformin therapy in type 2 diabetes.

Inhibition of miR-146a-5p and miR-8114 in Insulin-Secreting Cells Contributes to the Protection of Melatonin against Stearic Acid-Induced Cellular Senescence by Targeting Mafa.

BACKGRUOUND: Chronic exposure to elevated levels of saturated fatty acids results in pancreatic ß-cell senescence. However, targets and effective agents for preventing stearic acid-induced ß-cell senescence are still lacking. Although melatonin administration can protect ß-cells against lipotoxicity through anti-senescence processes, the precise underlying mechanisms still need to be explored. Therefore, we investigated the anti-senescence effect of melatonin on stearic acid-treated mouse ß-cells and elucidated the possible role of microRNAs in this process. METHODS: ß-Cell senescence was identified by measuring the expression of senescence-related genes and senescence-associated ß-galactosidase staining. Gain- and loss-of-function approaches were used to investigate the involvement of microRNAs in stearic acid-evoked ß-cell senescence and dysfunction. Bioinformatics analyses and luciferase reporter activity assays were applied to predict the direct targets of microRNAs. RESULTS: Long-term exposure to a high concentration of stearic acid-induced senescence and upregulated miR-146a-5p and miR- 8114 expression in both mouse islets and ß-TC6 cell lines. Melatonin effectively suppressed this process and reduced the levels of these two miRNAs. A remarkable reversibility of stearic acid-induced ß-cell senescence and dysfunction was observed after silencing miR-146a-5p and miR-8114. Moreover, V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (Mafa) was verified as a direct target of miR-146a-5p and miR-8114. Melatonin also significantly ameliorated senescence and dysfunction in miR-146a-5pand miR-8114-transfected ß-cells. CONCLUSION: These data demonstrate that melatonin protects against stearic acid-induced ß-cell senescence by inhibiting miR-146a- 5p and miR-8114 and upregulating Mafa expression. This not only provides novel targets for preventing stearic acid-induced ß-cell dysfunction, but also points to melatonin as a promising drug to combat type 2 diabetes progression.

Comparative analysis of circRNA expression profile and circRNA-miRNA-mRNA regulatory network between palmitic and stearic acid-induced lipotoxicity to pancreatic ß cells.

Chronic exposure to high concentrations of circulating palmitic acid and stearic acid leads to impaired ß cell function, which accelerates the development of type 2 diabetes. However, differences in the mechanisms underlying this process between these two saturated fatty acids remain largely unknown. In this study, we screened for potential circular RNAs (circRNAs) and their associated regulatory pathways in palmitic acid- and stearic acid-induced mouse ß-TC6 cell dysfunction. CircRNA high-throughput sequencing, gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes analysis were performed and co-expression and competing endogenous RNAs (ceRNA) networks were constructed. We identified that four circRNAs that were differentially expressed specifically in ß cells exposed to palmitic acid, whereas four circRNAs were differentially expressed specifically in ß cells exposed to stearic acid. Seven circRNAs were differentially co-expressed in palmitic acid- and stearic acid-treated ß cells. In pathway exploration, we identified the core protein Solute carrier family 2 member 2 (SLc2a2), which is mainly involved in insulin resistance, maturity onset diabetes of the young and type 2 diabetes. The expressions of key circRNAs in ß-TC6 cells were validated by Real time quantitative PCR, with a consistent result in high-throughput sequencing. The findings aid our understanding of the mechanisms governing the difference between palmitic acid- and stearic acid-induced ß cell dysfunction and provide potential therapeutic targets for developing treatments against long-term high fat diet-induced ß cell injury.Abbreviations: Acvr1c: Activin A receptor, type 1C; CeRNA, Competing endogenous RNAs; circRNA, circular RNA; DEcircRNA: Differentially Expressed circular RNA; DEmiRNA: Differentially Expressed microRNA; DEmRNA: Differentially Expressed mRNA; GO: Gene Ontology; HPDHigh Palmitic acid Diet; HSD: High Stearic acid Diet; KEGG: Kyoto Encyclopedia of Genes and Genomes; miRNA: microRNA; ncRNAs: non-coding RNAs; qPCR: Real time quantitative PCRS; FAs: Saturated Fatty Acids; SLc2a2: Solute carrier family 2 member 2; T2D: Type 2 Diabetes.

Inhibition of lncRNA TCONS_00077866 Ameliorates the High Stearic Acid Diet-Induced Mouse Pancreatic ß-Cell Inflammatory Response by Increasing miR-297b-5p to Downregulate SAA3 Expression.

Long-term consumption of a high-fat diet increases the circulating concentration of stearic acid (SA), which has a potent toxic effect on ß-cells, but the underlying molecular mechanisms of this action have not been fully elucidated. Here, we evaluated the role of long noncoding (lnc)RNA TCONS_00077866 (lnc866) in SA-induced ß-cell inflammation. lnc866 was selected for study because lncRNA high-throughput sequencing analysis demonstrated it to have the largest fold-difference in expression of five lncRNAs that were affected by SA treatment. Knockdown of lnc866 by virus-mediated shRNA expression in mice or by Smart Silencer in mouse pancreatic ß-TC6 cells significantly inhibited the SA-induced reduction in insulin secretion and ß-cell inflammation. According to lncRNA-miRNAs-mRNA coexpression network analysis and luciferase reporter assays, lnc866 directly bound to miR-297b-5p, thereby preventing it from reducing the expression of its target serum amyloid A3 (SAA3). Furthermore, overexpression of miR-297b-5p or inhibition of SAA3 also had marked protective effects against the deleterious effects of SA in ß-TC6 cells and mouse islets. In conclusion, lnc866 silencing ameliorates SA-induced ß-cell inflammation by targeting the miR-297b-5p/SAA3 axis. lnc866 inhibition may represent a new strategy to protect ß-cells against the effects of SA during the development of type 2 diabetes.

TCONS_00230836 silencing restores stearic acid-induced ß cell dysfunction through alleviating endoplasmic reticulum stress rather than apoptosis.

BACKGROUND: Chronic exposure of pancreatic ß cells to high levels of stearic acid (C18:0) leads to impaired insulin secretion, which accelerates the progression of type 2 diabetes mellitus (T2DM). Recently, long noncoding RNAs (lncRNAs) were found to participate in saturated fatty acid-induced metabolism dysfunction. However, their contribution to stearic acid-induced ß-cell dysfunction remains largely unknown. This study evaluated the possible role of the lncRNA TCONS_00230836 in stearic acid-stimulated lipotoxicity to ß cells. METHOD: Using high-throughput RNA-sequencing, TCONS_00230836 was screened out as being exclusively differentially expressed in stearic acid-treated mouse ß-TC6 cells. Co-expression network was constructed to reveal the potential mRNAs targeted for lncRNA TCONS_00230836. Changes in this lncRNA's and candidate mRNAs' levels were further assessed by real-time PCR in stearic acid-treated ß-TC6 cells and islets of mice fed a high-stearic-acid diet (HSD). The localization of TCONS_00230836 was detected by fluorescent in situ hybridization. The endogenous lncRNA TCONS_00230836 in ß-TC6 cells was abrogated by its Smart Silencer. RESULTS: TCONS_00230836 was enriched in mouse islets and mainly localized in the cytoplasm. Its expression was significantly increased in stearic acid-treated ß-TC6 cells and HSD-fed mouse islets. Knockdown of TCONS_00230836 significantly restored stearic acid-impaired glucose-stimulated insulin secretion through alleviating endoplasmic reticulum stress. However, stearic acid-induced ß cell apoptosis was not obviously recovered. CONCLUSION: Our findings suggest the involvement of TCONS_00230836 in stearic acid-induced ß-cell dysfunction, which provides novel insight into stearic acid-induced lipotoxicity to ß cells. Anti-lncRNA TCONS_00230836 might be a new therapeutic strategy for alleviating stearic acid-induced ß-cell dysfunction in the progression of T2DM.

Facile synthesis and catalytic property of porous tin dioxide nanostructures.

Porous tin dioxide (SnO(2)) nanostructures consisting of nanoplates are prepared through thermal decomposition of the mixed solution composed of dibutyltin dilaurate and acetic acid. The aggregations of the nanoplates give rise to large macropores with the size of about 100-300 nm. These nanoplates have a wormhole-like porous structure with the size of about 4 nm and possess high surface area. X-ray powder diffraction, transmission electron microscopy, scanning electron microscopy, infrared spectroscopy, and nitrogen sorption have been employed to characterize the obtained porous structures. It is found that the obtained nanostructures exhibit excellent catalytic activity toward methanol decomposition. Such porous structures with high surface area have promising industrial applications as catalysts.

Heterostructures with ZnSe sheaths coating on carbon submicrotubes: preparation, characterization, and formation mechanism.

We designed a feasible one-step process to synthesize heterostructures with inorganic functional materials coating on carbon submicrotubes under a mild condition. The heterostructures of carbon submicrotubes with ZnSe sheaths were successfully synthesized through the polymerization-carbonization-coating process with glucose as both the carbon source and the reductive reagent and ammonia providing an alkaline environment and acting as a soft template. The compositions of the as-obtained product were confirmed by Raman spectroscopy and XRD measurement; the morphology and microstructure were studied by SEM, TEM, and HRTEM. Room-temperature photoluminescence (PL) measurement indicates the as-prepared tubular heterostructures have a sharp and well-resolved NBE emission centered at 436 nm besides the DL emission at 589 nm, which is possibly caused by the interface associated with the combination of carbon submicrotube and ZnSe nanocrystal. One of the advantages in this process is that glucose and ammonia play manifold roles in the formation of the submicroscaled tubular heterostructures. This suggests a new path for convenient synthesis of novel tubular heterostructures with inorganic functional materials attached on carbon tubes. Furthermore, this kind of tubular heterostructure may be an ideal system applied in the fabrication of submicroscaled optoelectronics devices, and investigations on its physical properties could extend the understanding of the structure-property relationships in solids, which are in progress.

Formation of a novel 1D supramolecule [HgCl2(ptz)]2.HgCl2 (ptz = phenothiazine): a new precursor to submicrometer Hg2Cl2 rods.

A novel supramolecule [HgCl(2)(ptz)](2).HgCl(2) (ptz = phenothiazine) with uncoordinated inorganic salt HgCl(2) presented in a 1D chain was first prepared and then successfully applied as a new precursor in the preparation of submicrometer Hg(2)Cl(2) rods. Single crystal X-ray analysis showed that the 1D chain structure is stabilized by hydrogen bonds between adjacent chains and the coordination mode of the ligand phenothiazine is unusual with large steric inhibition other than the chain directions. The results revealed that the particular chain structure plays a significant role in the formation of the Hg(2)Cl(2) rods.