A solid-state synthetic strategy toward nickel-based bimetallic interstitial compounds (MNi3Cx, M = Zn, In, Ga).

Bimetallic interstitial compounds with unique geometric properties have attracted increasing attention in energy-related fields and diverse chemical transformations. Current synthesis of these compounds generally involves at least one wet-chemistry step with the use of various solvents to prepare the bimetallic precursors, and no universal protocols for different compositions are yet available. Herein, a novel synthetic strategy toward a platform of nickel-based bimetallic interstitial compounds with the formula MNi3Cx, M = Zn, In, and Ga, was developed based on a straightforward solid-state transformation, i.e., simply annealing the hydroxides of the respective metals in the presence of different carbon precursors (cyanamide, dicyandiamide, melamine, and urea) in a hydrogen stream. The key process parameters influencing the compositions of the final products are studied and the formation mechanism is discussed based on advanced characterization techniques. Powder X-ray diffraction reveals MNi3Cx as a single phase and electron microscopy shows that the MNi3Cx particles are covered with N-doped carbon shells. Extrapolation to other bimetallic interstitial compounds failed when following the above protocol, and the successful examples are linked to the formation of the corresponding bimetallic alloys in the absence of carbon precursors. When evaluated for the selective hydrogenation of dimethyl oxalate, both InNi3C0.5 and ZnNi3C0.7 show comparable high activity. While ZnNi3C0.7 delivers the highest selectivity for methyl glycolate, tunable methyl glycolate and ethylene glycol are formed on InNi3C0.5. In general, this facile solvent-free strategy affords an interesting scaffold to fabricate more advanced multi-metallic interstitial compounds with broad applications.

UBIAD1 effectively alleviated myocardial ischemia reperfusion injury by activating SIRT1/PGC1α.

BACKGROUND AND OBJECTIVES: Myocardial ischemia-reperfusion injury (MIRI) threatens global health and lowers people's sense of happiness. Till now, the mechanism of MIRI has not been well-understood. Therefore, this study was designed to explore the role of UBIAD1 in MIRI as well as its detailed reaction mechanism. METHODS: The mRNA and protein expressions of UBIAD1 before or after transfection were measured using RT-qPCR and western blot. Western blot was also adopted to measure the expressions of signaling pathway-, mitochondrial damage- and apoptosis-related proteins. Moreover, mitochondrial membrane potential and ATP level were verified by JC-1 immunofluorescence and ATP kits, respectively. With the application of CCK-8, LDH and CK-MB assays, the cell viability, LDH and CK-MB levels were evaluated, respectively. In addition, the cell apoptosis was detected using TUNEL. Finally, the expressions of ROS, SOD, MDA and CAT were measured using DCFH-DA, SOD, MDA and CAT assays, respectively. RESULTS: In the present study, we found that UBIAD1 was downregulated in hypoxia-reoxygenation (H/R) -induced H9C2 cells and its upregulation could activate SIRT1/PGC1α signaling pathway. It was also found that UBIAD1 regulated mitochondrial membrane potential and ATP level via activating SIRT1/PGC1α signaling pathway. In addition, the injury of H/R-induced H9C2 cells could be relieved by UBIAD1 through the activation of SIRT1/PGC1α signaling pathway. Moreover, UBIAD1 exhibited inhibitory effects on apoptosis and oxidative stress of H/R-induced H9C2 cells through activating SIRT1/PGC1α signaling pathway. CONCLUSION: To sum up, UBIAD1 could alleviate apoptosis, oxidative stress and H9C2 cell injury by activating SIRT1/PGC1α, which laid experimental foundation for the clinical treatment of MIRI.

Dapagliflozin Improves Diabetic Cardiomyopathy by Modulating the Akt/mTOR Signaling Pathway.

Background: Dapagliflozin can significantly improve heart failure, and Cx43 is one of the molecular mechanisms of heart failure. This study investigated the effect of dapagliflozin on Cx43 and Akt/mTOR signaling pathway in ventricular myocytes. Methods: A rat model of type 2 diabetes mellitus was established by high-fat diet combined with streptozotocin, and the animals were treated randomly with dapagliflozin. The morphological changes of the myocardium were observed by hematoxylin eosin staining, and the expression and distribution of Cx43 in ventricular myocytes were detected by immunohistochemistry. And Western blot determined the expressions of Cx43, Akt, mTOR, p62, and LC3 proteins in rat myocardium. Results: Compared with the normal control group, the heart rate of diabetic rats decreased significantly (p < 0.05), QRS wave of ECG widened, and QT interval prolonged (p < 0.05). Dapagliflozin treatment in diabetic rats resulted in improvements in these ECG indexes (p < 0.05) with early administration group obtaining greater efficacy than the late administration group (p < 0.05). In the normal control group, the cardiomyocytes were arranged orderly, and the expression of Cx43 was dense, uniform, and regular, which was higher than that in the intercalated disc. In the diabetic control model group, the cardiomyocytes were enlarged and presented disorderly with detection of Cx43 in the cytoplasm. Early use of dapagliflozin better improved these myocardial tissue lesions. Of note, as diabetic rats exhibited decreased expression of Cx43, Akt, and mTOR (p < 0.05), increased p62 expression (p < 0.05), and decreased LC3-II/I ratio (p < 0.05), administration of dapagliflozin partially reversed the expression of the above proteins (p < 0.05) with greater improvement in the early administration group compared with the late administration group (p < 0.05). Conclusions: Dapagliflozin increases the expression of Cx43 in cardiomyocytes of diabetic rats and thereby alleviates heart failure partly through regulating the Akt/mTOR signaling pathway.