Sepsis-associated acute kidney injury (SAKI), a common complication in intensive care units (ICUs), is linked to high morbidity and mortality. Sirtuin 2 (SIRT2), an NAD⁺-dependent deacetylase, has been shown to have distinct effects on autophagy regulation compared to other sirtuins, but its role in SAKI remains unclear. This study explored the potential of SIRT2 as a therapeutic target for SAKI. We found that inhibition of SIRT2 with the antagonist AGK2 improved the survival of septic mice. SIRT2 inhibition reduced kidney injury, as indicated by lower levels of KIM-1, NGAL, serum creatinine, blood urea nitrogen, and proinflammatory cytokines following cecal ligation and puncture. Pretreatment with AGK2 in septic mice increased autophagosome and autolysosome formation in renal tubular epithelial cells and upregulated LC3 II expression in the renal cortex. Consistent with in vivo findings, SIRT2 gene silencing promoted autophagy in LPS-treated HK-2 cells, whereas SIRT2 overexpression inhibited it. Mechanistically, SIRT2 inhibition increased FOXO1 acetylation, inducing its nuclear-to-cytoplasmic translocation, which promoted kidney autophagy and alleviated SAKI. Our study suggests SIRT2 as a potential target for SAKI therapy.

Background: Endothelial cells are the first and most damaged target cells during acute lung injury (ALI). Endothelial dysfunction increases pulmonary microvascular permeability, subsequently leading to pulmonary oedema and organ dysfunction; however, clinical treatments against microvascular permeability show poor efficacy. Herein, we aimed to explore the role of the Sigma-1 receptor (Sig-1R) in pulmonary microvascular permeability by constructing ALI animal and cell models, and further investigated the specific mechanisms. Methods: The effects of Sig-1R on lung injury and endothelial barrier disruption were examined in lipopolysaccharide (LPS)-induced mice and human umbilical vein endothelial cells (HUVECs), respectively. Transcriptome sequencing was carried out to identify possible targets of Sig-1R, and the specific mechanisms of Sig1R action were investigated using RNA interference and plasmid transfection. Results: Analysis of a Gene expression omnibus dataset suggested that Sig-1R plays a protective role against vascular hyperpermeability in ALI. Downregulation of Sig-1R expression and endothelial barrier disruption were both observed in mice and HUVECs upon LPS stimulation. Sig-1R agonists attenuated vascular hyperpermeability in vivo and in vitro, further improving ALI. Sig-1R activation downregulated Leucine-rich repeat kinase 2 (LRRK2) expression in mice and HUVECs. LRRK2 knockdown ameliorated endothelial barrier disruption in mice and HUVECs. Overexpression of LRRK2 reversed the protective effect of Sig-1R activation on LPS-induced endothelial hyperpermeability. Furthermore, Sig1r knockdown exacerbated LPS-induced microvascular hyperpermeability, which was rescued by inhibition of LRRK2. Conclusions: Sig-1R activation exerts a protective effect against LPS-induced microvascular hyperpermeability by downregulating LRRK2 expression, which could lead to the development of novel therapeutic strategies for treating ALI.

Objective: To assess the efficacy and safety of visual rigid laryngoscopy and video laryngoscopy and to provide clinical information for developing a more suitable intubation tool for elderly patients. Methods: In 75 consecutive elderly patients undergoing elective surgery in a single institution, tracheal intubation was randomly performed by 2 experienced anaesthesiologists using visual rigid laryngoscopy (Group I, n = 38) or video laryngoscopy (Group II, n = 37). The primary outcome was intubation time. Secondary outcomes were the first-attempt success rate of tracheal intubation, haemodynamic responses at 1, 3, and 5 min after intubation and the incidence of postoperative airway complications, including immediate complications and postoperative complaints. Results: The intubation times were 35.0 (30.0–41.5) s and 42.5 (38.0–51.3) s in Groups I and II, respectively (P < 0.001). The difference in direct complications between the two groups was statistically significant (P < 0.05). In contrast, there was no significant difference between the two groups regarding the follow-up of the main complaint 30 min and 24 h after tracheal extubation (P > 0.05). There was no difference in the intubation success rate between the 2 groups (P > 0.05). The haemodynamic responses at 1, 3, and 5 min after intubation were not significantly different (P > 0.05). Conclusion: Compared with that of video laryngoscopy, the intubation time of visual rigid laryngoscopy in elderly patients was shorter. At the same time, visual rigid laryngoscopy reduced the incidence of immediate complications. However, during endotracheal intubation, there was no significant difference in haemodynamics between the two groups. Clinical trial registration number: ChiCTR2100054174.

Perfluoroundecanoic acid (PFUnA) is a long-chain perfluoroalkyl substance. However, whether PFUnA affects liver development during puberty is still unclear. Male 35-day-old Sprague-Dawley rats were gavaged with 0 (corn oil), 1, 5, and 10 mg/kg/day of PFUnA for 21 days. Liver weight was remarkably increased by PFUnA at ≥1 mg/kg, while serum alanine aminotransferase levels were higher at 5 and 10 mg/kg. PFUnA upregulated the expression of Lxrα, Hmgcr, Srebp2, and Cyp7a1 and downregulated the expression of Abcg8, Ldlr, Sod1, and Cat. These changes were also confirmed at the protein level. It increased the release of inflammatory factors (IL-1β, IL-6, and TNF-α). It also downregulated the fibrosis-related gene expression of Adamts6 and Col4a1. Similar results were obtained in HepG2 cells treated with 50 μM PFUnA in vitro. PFUnA induced oxidative stress and perturbed lipid metabolism. Overall, PFUnA may induce oxidative stress and disrupt lipid metabolism to have an inhibitory influence on pubertal liver development.