CircRNA DICAR as a novel endogenous regulator for diabetic cardiomyopathy and diabetic pyroptosis of cardiomyocytes

In this study,we identified that a conserved circular RNA(circRNA)DICAR,which was downregulated in diabetic mouse hearts.DICAR had an inhibitory effect on diabetic cardiomyopathy(DCM),as the spontaneous cardiac dysfunction,cardiac cell hypertrophy,and cardiac fibrosis occurred in DICAR deficiency(DICAR+/−)mice,whereas the DCM was alleviated in DICARoverexpressed DICARTg mice.At the cellular level,we found that overexpression of DICAR inhibited,but knockdown of DICAR enhanced the diabetic cardiomyocyte pyroptosis.At the molecular level,we identified that DICAR-VCP-Med12 degradation could be the underlying molecular mechanism in DICAR-mediated effects.The synthesized DICAR junction part(DICAR-JP)exhibited a similar effect to the entire DICAR.In addition,the expression of DICAR in circulating blood cells and plasma from diabetic patients was lower than that from health controls,which was consistent with the decreased DICAR expression in diabetic hearts.DICAR and the synthesized DICAR-JP may be drug candidates for DCM.

Total Synthesis of C-α-Mannosyl Tryptophan via Palladium-Catalyzed C-H Glycosylation

The C2-α-mannosyl-tryptophan amino acid is produced by a unique posttranslational modification(PTM)of proteins and poses a significant synthetic challenge.A new strategy based on Pd-catalyzed auxiliary-directed remote C-H glycosylation of tryptophan was developed,which generates the C2-α-mannopyranose(Man)-Trp unit in a highly efficient and stereoselective fashion.Density functional theory(DFT)computational studies support a concerted oxidative addition mechanism for the stereospecific functionalization of a Pd(II)palladacycle intermediate with anα-mannosyl chloride donor.The utility of this method was demonstrated in the first total synthesis of insect C-glycopeptide hormone Cam-HrTH-I.