Hepatic ischemia-reperfusion (I/R) injury is a common complication in liver transplantation. The connection between I/R-induced injury response and liver heterogeneity has yet to be fully understood. In this study, we converge histopathological examination with spatial transcriptomics to dissect I/R injury patterns and their associated molecular changes, which reveal that the pericentral zones are most sensitive to I/R injury in terms of histology, transcriptomic changes, and cell type dynamics. Bioinformatic analysis of I/R injury-related pathways predicts that celastrol can protect against liver I/R injury by inducing ischemic pre-conditioning, which is experimentally validated. Mechanistically, celastrol likely implements its protective effect against I/R injury by activating HIF1α signaling and represents a potential strategy for resolving liver I/R.
Efficient
regioselective synthesis of novel fully substituted pyrazoles
has been achieved through Huisgen cycloaddition reaction of δ-acetoxy
allenoates with hydrazonoyl chlorides by the addition of Ag2O. The present approach offers the advantages of simpleness, high
efficiency, mild conditions, wide substrate scope, and good-to-excellent
regioselectivities. The strategy could be performed on a large-scale
pattern to allow access to structurally versatile pyrazoles, of which
a key intermediate of lonazolac (303), a nonsteroidal anti-inflammatory
drug, could be synthesized efficiently. Moreover, several pyrazoles
show obvious growth-inhibitory activity of Huh-7 cells, expected as
potential anticancer agents.
Copper mediated coupling of fluoro‐alkylamines/trifluoroacetamide and aryl‐boronic acids have been developed. N‐arylation of di/trifluoroethylamine was achieved by a Cu(OAc)2/Py system with AgNO3 as an additive, while the N‐arylation of trifluoroacetamide was described with Cu(OAc)2/TEA system. These protocols could tolerate a variety of functional groups of hetero/aryl‐boronic acids, furnishing the corresponding products with moderate to good yields under mild and simple conditions.
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