Chemoselective Quinoline and Isoquinoline Reduction by Energy Transfer Catalysis Enabled Hydrogen Atom Transfer.

(Hetero)arene reduction is one of the key avenues for synthesizing related cyclic alkenes and alkanes. While catalytic hydrogenation and Birch reduction are the two broadly utilized approaches for (hetero)arene reduction across academia and industry over the last century, both methods have encountered significant chemoselectivity challenges. We hereby introduce a highly chemoselective quinoline and isoquinoline reduction protocol operating through selective energy transfer (EnT) catalysis, which enables subsequent hydrogen atom transfer (HAT). The design of this protocol bypasses the conventional metric of reduction reaction, that is, the reductive potential, and instead relies on the triplet energies of the chemical moieties and the kinetic barriers of energy and hydrogen atom transfer events. Many reducing labile functional groups, which were incompatible with previous (hetero)arene reduction reactions, are retained in this reaction. We anticipate that this protocol will trigger the further advancement of chemoselective arene reduction and enable the current arene-rich drug space to escape from flatland.

Analysis of time-series gene expression data to explore mechanisms of isoniazid-induced liver toxicity.

Isoniazid (INH) is a first-line anti-tuberculosis drug which can cause idiosyncratic liver injury, while the underlying mechanisms need to be further elucidated. In this study, we explored the time series gene expression profiling of a hepatocyte cell line under isoniazid treatment. Through cluster analysis and enrichment analysis of differentially expressed genes, we revealed a total of 6 gene clusters and a series of pathways related to hepatotoxicity, and 13 key candidate genes were identified according to the protein-protein interaction (PPI) network analysis and maSigPro analysis. These findings lay a foundation for understanding the mechanisms of isoniazid -induced liver toxicity and provide new target genes for the monitoring and treatment of INH-induced hepatotoxicity in the future.

Jasmonic acid and hydrogen sulfide modulate transcriptional and enzymatic changes of plasma membrane NADPH oxidases (NOXs) and decrease oxidative damage in Oryza sativa L. during thiocyanate exposure.

It is evident that the plasma membrane NADPH oxidases (NOXs) play an important role in the generation of superoxide radicals (O2-•) in plants during defense responses. This study was to clarify activation of NOXs in oxidative damage in Oryza sativa during SCN- exposure, particularly in the roles of jasmonic acid (JA) and hydrogen sulfide (H2S) on transcriptional and enzymatic changes of NOXs. Results indicated that enzymatic activity of NOXs in both roots and shoots was significantly enhanced during SCN- exposure, whereas the application of JA and H2S donor (NaHS) significantly repressed NOXs activity in SCN-treated rice seedlings. Similarly, ROS analysis showed that SCN- exposure elevated the content of O2-•, hydrogen peroxide (H2O2) and malondialdehyde (MDA) in rice tissues significantly, whereas decreases in O2-• and H2O2 were detected in roots and shoots of SCN-treated rice seedlings due to application of JA and NaHS. PCR analysis revealed different expression patterns of 7 plasma membrane-localized NOX genes in rice roots and shoots against SCN- exposure, suggesting that various isogenes of NOXs might regulate and determine activity of NOXs in rice organs. In conclusion, SCN- exposure was able to trigger activation of NOXs effectively, and led to oxidative damage and lipid peroxidation; the effects of JA and NaHS on inactivation of NOXs was evident and tissue specific, which in turn modulated ROS accumulation in rice plants.