Search

Acetaminophen (APAP) overdose is a major cause of drug‐induced liver injury. Sirtuins 5 (SIRT5) has been implicated in the development of various liver diseases. However, its involvement in APAP‐induced acute liver injury (AILI) remains unclear. The present study aimed to explore the role of SIRT5 in AILI. SIRT5 expression is dramatically downregulated by APAP administration in mouse livers and AML12 hepatocytes. SIRT5 deficiency not only exacerbates liver injury and the inflammatory response, but also worsens mitochondrial oxidative stress. Conversely, the opposite pathological and biochemical changes are observed in mice with SIRT5 overexpression. Mechanistically, quantitative succinylome analysis and site mutation experiments revealed that SIRT5 desuccinylated aldehyde dehydrogenase 2 (ALDH2) at lysine 385 and maintained the enzymatic activity of ALDH2, resulting in the suppression of inflammation and mitochondrial oxidative stress. Furthermore, succinylation of ALDH2 at lysine 385 abolished its protective effect against AILI, and the protective effect of SIRT5 against AILI is dependent on the desuccinylation of ALDH2 at K385. Finally, virtual screening of natural compounds revealed that Puerarin promoted SIRT5 desuccinylase activity and further attenuated AILI. Collectively, the present study showed that the SIRT5‐ALDH2 axis plays a critical role in AILI progression and might be a strategy for therapeutic intervention. [ABSTRACT FROM AUTHOR]

The electroreduction of carbon dioxide (CO2) to multi‐carbon (C2+) compounds offers a viable approach for the up‐conversion of greenhouse gases into valuable fuels and feedstocks. Nevertheless, current industrial applications face limitations due to unsatisfactory conversion efficiency and high overpotential. Herein, a facile and scalable plasma fluorination method is reported. Concurrently, self‐evolution during CO2 electroreduction is employed to control the active sites of Cu catalysts. The copper catalyst modified with fluorine exhibits an impressive C2+ Faradaic efficiency (FE) of 81.8% at a low potential of −0.56 V (vs a reversible hydrogen electrode) in an alkaline flow cell. The presence of modified fluorine leads to the exposure and stabilization of high‐activity Cu+ species, enhancing the adsorption of *CO intermediates and the generation of *CHO, facilitating the subsequent dimerization. This results in a notably improved conversion efficiency of 13.1% and a significant reduction in the overpotential (≈100 mV) for the C2+ products. Furthermore, a superior C2+ FE of 81.6% at 250 mA cm−2, coupled with an energy efficiency of 31.0%, can be achieved in a two‐electrode membrane electrode assembly electrolyzer utilizing the fluorine‐modified copper catalyst. The strategy provides novel insights into the controllable electronic modification and surface reconstruction of electrocatalysts with practical potential. [ABSTRACT FROM AUTHOR]