Objective. Acute kidney injury (AKI) is a common and severe complication in critically ill patients, often caused by renal ischemia-reperfusion (RIR). Previous studies have confirmed that lung injury, rather than renal injury, is one of the leading causes of AKI-induced death. The pathophysiological mechanisms of acute lung injury (ALI) resulting from AKI are very complex and remain unclear. In the present study, we aimed to explore the protective effects and potential mechanism of sodium hydrosulfide (NaHS) on lung injury in RIR mice. Methods. The RIR model was established in wild-type and Nrf2-/- mice. Different groups of mice were treated with NaHS and MCC950. Lung tissues were harvested to detect lung injury, mitochondrial function, cell apoptosis, the NLRP3 inflammasome, and Nrf2 pathway-related molecules. Results. RIR led to a deterioration in lung histology, the wet/dry weight ratio, PaO2/FiO2, and mitochondrial function, in addition to stimulating the activation of the NLRP3 and Nrf2 pathways. MCC950 alleviated mitochondrial dysfunction, lung apoptosis, and histology injury in the lungs after RIR. NaHS treatment markedly improved the lung histological scores, the wet/dry weight ratio, bronchoalveolar lavage fluid (BALF) cell counts, BALF neutrophil counts, BALF neutrophil elastase activity, BALF protein concentration, PaO2/FiO2, mitochondrial morphology, the red/green fluorescence intensity that indicates changes in mitochondrial membrane potential, respiratory control rate (RCR), ATP, reactive oxygen species (ROS) release, and cell apoptosis via Nrf2-mediated NLRP3 pathway inhibition. Conclusion. NaHS protected against RIR-induced lung injury, mitochondrial dysfunction, and inflammation, which is associated with Nrf2 activation-mediated NLRP3 pathway inhibition.

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Background: Aberrant alternative splicing (AS) is involved in many oncogenic processes and systematic analysis of survival-associated aberrant AS events has been reported in many cancers. This study aims to systematic profiling the AS signature in Adrenocortical carcinoma (ACC).Methods: Data of ACC were downloaded from TCGA and TCGA SpliceSeq. Clinical information and AS events data were integrated with the same TCGA ID. Then, we performed univariate Cox analysis to identify survival-related AS events. Lasso regression and multivariate Cox analysis were used to establish prognostic model. In addition, several bioinformatics analyses were conducted to identify pathways enriched by genes of survival-associated AS events and construct splicing-factor-regulated network.Results: A total of 77 patients with complete clinical information and PSI values of AS events were included in the present study. We detected 3781 AS events in 2366 genes were associated with overall survival of ACC patients. All the predictive models showed efficiency in distinguishing good and poor outcomes of ACC patients. All the AUCs of predictive models were greater than 0.7. Functional analysis genes with survival-associated AS events suggested that the POLR2H, TCEB2, PSMA1, PSMD11 and SKP2 ranked at the core. The splicing-factor-regulated network revealed the potential regulatory mechanisms of AS events in ACC.Conclusions: Our systematic profiling of survival-associated AS events in ACC patients provides novel molecular alternations and contributes to decipher the underlying mechanisms of AS in oncogenesis of ACC.