Rhodium-catalyzed annulation of hydrazines with vinylene carbonate to synthesize unsubstituted 1-aminoindole derivatives.

Herein, we describe rhodium-catalysed C-H bond activation for [3 + 2] annulation using hydrazide and vinylene carbonate, providing an efficient method for synthesising unsubstituted 1-aminoindole compounds. Characterised by high yields, mild reaction conditions, and no need for external oxidants, this transformation demonstrates excellent regioselectivity and a wide tolerance for various functional groups.

Effects of the Lipid Metabolites and the Gut Microbiota in ApoE-/- Mice on Atherosclerosis Co-Depression From the Microbiota-Gut-Brain Axis.

Background: The diagnosis, treatment, and prevention of atherosclerosis co-depression are poor, so it is urgent to explore new targets. Based on the "microbiota-gut-brain axis," this study aimed to investigate the changes of lipid metabolites in the prefrontal cortex and hippocampus regions and the characteristics of the gut microbiota in ApoE-/- mice with atherosclerosis co-depression. Methods: ApoE-/- mice (hyperlipid feeding combined with binding, HFB group, n = 14, male) fed a high-fat diet for 16 weeks with binding stimulation were used as an animal model for atherosclerosis co-depression. The depression degree of mice was evaluated by body weight, sucrose preference test, open field test, and tail suspension test. Oil-red O staining, HE staining, and biochemical parameters were used to evaluate the damage degree of atherosclerosis in mice. LC-MS/MS technique for non-targeted lipidomics analysis was used to analyze the differential lipid metabolites in the prefrontal cortex and hippocampus regions of mice. 16S rDNA amplification sequencing was used to screen the differential gut microbial, and association analysis was performed with the differential lipid metabolites. Results: Compared with the normal control group (NC group), the HFB group showed depression-like behaviors and atherosclerosis-related pathological indicators. The differential lipid metabolites in the prefrontal cortex and hippocampus regions were mainly LPC, LPE, LPS, PC, PE, PS, PI, and GD1a, and were mainly enriched in the glycerophospholipid metabolism pathway and the retrograde endocannabinoid signaling pathway. At the same time, there were significant differences in the structure of the gut microbial community between the two groups. The abundance of Deferribacteres and Proteobacteria in the HFB group increased, while the abundance of Verrucomicrobia and Actinobacteria decreased at the phylum level; the abundance of Desulfovibrio, Clostridium_IV, Helicobacter and Pseudoflavonifractor increased, while the abundance of Akkermansia decreased at the genus level. Conclusion: Atherosclerosis co-depression of ApoE-/- mice of the prefrontal cortex and hippocampus lipid metabolism pathways of disorder and the changes of to the gut microbiota, which leads to abnormal white matter and synaptic dysfunction, increased gut inflammation, and decreased gut permeability, leading to the release of inflammatory cytokines, there is a strong correlation between both, it further confirmed the existence of the "microbiota-gut-brain axis."

Morroniside alleviates coxsackievirus B3-induced myocardial damage apoptosis via restraining NLRP3 inflammasome activation.

Coxsackievirus B3 (CVB3)-induced myocardial damage always leads to serious heart failure by inducing cardiac injury. NLRP3 inflammasome activation has been identified as a central player in the pathogenesis of CVB3-induced viral myocarditis. Therefore, restraining NLRP3 inflammasome activation has been supposed to significantly alleviate the severity of myocardial damage and improve cardiac function. Morroniside (MR), one of the main iridoid glycosides, has the ability to depress the production of reactive oxygen species (ROS) and restrain the expression of caspase-3 and -9. Of importance, ROS and caspase are essential for NLRP3 inflammasome activation in response to CVB3 infection. Therefore, in the present study, MR was selected as a model drug to alleviate CVB3-induced myocardial damage. The results of cardiac function index determination showed that abnormal indexes including mean arterial pressure, heart rate, and left ventricular systolic pressure of myocardial damage rats could be recovered by treating with MR. Such results can be further verified by histopathological evaluation, with the heart tissues of CVB3-infected rats displaying the most amount of H&E and TUNEL positive cells. The underlying mechanism by which MR improves the cardiac function was subsequently investigated. The detection of various gene levels indicated that NLRP3 inflammasome activation was inhibited by MR through down-regulating the expression of pro-inflammatory cytokines: interleukin (IL)-ß and IL-18, the pivotal factors that lead to inflammatory responses. More importantly, the related genes, cardiac function indexes, and various myocardial damage markers of normal rats treated with MR did not exhibit any obvious changes compared with the control group, indicating a satisfactory biocompatibility of MR. In summary, MR holds a great potential in the alleviation of CVB3-induced myocardial damage with a negligible cytotoxicity to normal heart tissues.