Background and aims: Macrophages play a critical role in the development of liver diseases. As an NAD⁺-dependent histone deacetylase, SIRT1 inhibits liver inflammation and fibrosis, but the mechanisms are not fully understood. Our aim was to investigate the molecular mechanism of SIRT1 in macrophages in liver inflammation and fibrosis.

Progerin, a permanently farnesylated prelamin A protein in cell nuclei, is potentially implicated in the defenestration of liver sinusoidal endothelial cells (LSECs) and liver fibrogenesis. Autophagy regulates the degradation of nuclear components, called nucleophagy, in response to damage. However, little is known about the role of nucleophagy in LSEC defenestration. Herein, we aim to dissect the underlying mechanism of progerin and nucleophagy in LSEC phenotype. We found an abnormal accumulation of progerin and a loss of SIRT1 in the nucleus of intrahepatic cells in human fibrotic liver tissue. In vivo, nuclear progerin abnormally accumulated in defenestrated LSECs, along with a depletion of SIRT1 and Cav-1 during liver fibrogenesis, whereas these effects were reversed by the overexpression of SIRT1 with the adenovirus vector. In vitro, H₂O₂ induced the excessive accumulation of progeirn, with the depletion of Lamin B1 and Cav-1 to aggravate LSEC defenestration. NAC and mito-TEMPO, classical antioxidants, inhibited NOX2- and NOX4-dependent oxidative stress to improve the depletion of Lamin B1 and Cav-1 and promoted progerin-related nucleophagy, leading to a reverse in H₂O₂-induced LSEC defenestration. However, rapamycin aggravated the H₂O₂-induced depletion of Lamin B1 and Cav-1 due to excessive autophagy, despite promoting progerin nucleophagic degradation. In addition, overexpressing SIRT1 with the adenovirus vector inhibited oxidative stress to rescue the production of Lamin B1 and Cav-1. Moreover, the SIRT1-mediated deacetylation of nuclear LC3 promoted progerin nucleophagic degradation and subsequently inhibited the degradation of Lamin B1 and Cav-1, as well as improved F-actin remodeling, contributing to maintaining LSEC fenestrae. Hence, our findings indicate a new strategy for reversing LSEC defenestration by promoting progerin clearance via the SIRT1-mediated deacetylation of nuclear LC3.

Background: Reducing the length of stay (LOS) for patients hospitalized with inflammatory bowel disease is crucial for lowering healthcare costs and improving patients’ quality of life. However, the determinant factors of LOS in ulcerative colitis (UC) patients are incompletely understood. Methods: Participants were obtained from the Henan Provincial People’s Hospital during the period from January 2018 to April 2025. Information on multidimensional determinants of LOS was collected using a questionnaire. Spearman correlation analysis and negative binomial regression models were performed to identify factors associated with LOS. A subgroup analysis was performed to examine the disease stage and severity in relation to LOS. The interaction of identifying factors was analyzed. Results: A total of 400 active UC-related hospitalizations were identified. Correlation analysis showed that LOS was positively correlated with mMayo score, improved Mayo endoscopic score, white blood cell count, platelet, C-reactive protein, and gamma-glutamyl transferase levels. However, LOS was negatively correlated with red blood cell count, hemoglobin, albumin, and total cholesterol levels. A negative binomial regression model showed that albumin reduction was associated with prolonged LOS in active UC patients, regardless of disease severity. Decreases in albumin level and Connor–Davidson Resilience Scale score were associated with increased LOS, and their corresponding estimated incidence rate ratios and 95% confidence intervals were 0.967 (0.937, 0.997) and 0.434 (0.188, 1.003), respectively. An interaction of these variables on LOS was observed in the remission stage of patients. Conclusion: This study found that lower serum albumin levels were significantly associated with a longer LOS in patients with active UC. Furthermore, both lower albumin levels and poorer psychological resilience were associated with prolonged LOS. This study’s findings suggest that albumin optimization may be an effective strategy for reducing LOS in active UC, and further integrating psychological resilience–building interventions into standard care could help shorten hospitalization and improve outcomes for patients in remission.