Although clinical evidence suggests that nonalcoholic fatty liver disease is an established major risk factor for heart failure, it remains unexplored whether sleep disorder-caused hepatic damage contributes to the development of cardiovascular disease (CVD). Here, our findings revealed that sleep fragmentation (SF) displayed notable hepatic detrimental phenotypes, including steatosis and oxidative damage, along with significant abnormalities in cardiac structure and function. All these pathological changes persisted even after sleep recovery for 2 consecutive weeks or more, displaying memory properties. Mechanistically, persistent higher expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in the liver was the key initiator of SF-accelerated damage phenotypes. SF epigenetically controlled the acetylation of histone H3 lysine 27 (H3K27ac) enrichment at the Nox4 promoter and markedly increased Nox4 expression in liver even after sleep recovery. Moreover, fine coordination of the circadian clock and hepatic damage was strictly controlled by BMAL1-dependent Sirtuin 1 (Sirt1) transcription after circadian misalignment. Accordingly, genetic manipulation of liver-specific Nox4 or Sirt1, along with pharmacological intervention targeting NOX4 (GLX351322) or SIRT1 (Resveratrol), could effectively erase the epigenetic modification of Nox4 by reducing the H3K27ac level and ameliorate the progression of liver pathology, thereby counteracting SF-evoked sustained CVD. Collectively, our findings may pave the way for strategies to mitigate myocardial injury from persistent hepatic detrimental memory in diabetic patients.

Acute lung injury (ALI) has been a kind of acute and severe disease that is mainly characterized by systemic uncontrolled inflammatory response to the production of huge amounts of reactive oxygen species (ROS) in the lung tissue. Given the critical role of ROS in ALI, a Fe₃O₄ loaded bovine serum albumin (BSA) nanocluster (BF) was developed to act as a nanomedicine for the treatment of ALI. Combining with NIR irradiation, it exhibited excellent ROS scavenging capacity. Significantly, it also displayed the excellent antioxidant and anti-inflammatory functions for lipopolysaccharides (LPS) induced macrophages (RAW264.7), and Sprague Dawley rats via lowering intracellular ROS levels, reducing inflammatory factors expression levels, inducing macrophage M2 polarization, inhibiting NF-κB signaling pathway, increasing CD4⁺/CD8⁺ T cell ratios, as well as upregulating HSP70 and CD31 expression levels to reprogram redox homeostasis, reduce systemic inflammation, activate immunoregulation, and accelerate lung tissue repair, finally achieving the synergistic enhancement of ALI immunotherapy. It finally provides an effective therapeutic strategy of BF + NIR for the management of inflammation related diseases.

Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO2-induced cardiac injury using a mouse model. Methods Male C57BL/6 mice were intratracheally instilled with SiO2 to create a silicosis model.Ferrostatin-1(Fer-1)and deferoxamine(DFO)were used to suppress ferroptosis.Serum biomarkers,oxidative stress markers,histopathology,iron content,and the expression of ferroptosis-related proteins were assessed. Results SiO2 altered serum cardiac injury biomarkers,oxidative stress,iron accumulation,and ferroptosis markers in myocardial tissue.Fer-1 and DFO reduced lipid peroxidation and iron overload,and alleviated SiO2-induced mitochondrial damage and myocardial injury.SiO2 inhibited Nuclear factor erythroid 2-related factor 2(Nrf2)and its downstream antioxidant genes,while Fer-1 more potently reactivated Nrf2 compared to DFO. Conclusion Iron overload-induced ferroptosis contributes to SiO2-induced cardiac injury.Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO2 cardiotoxicity,potentially via modulation of the Nrf2 pathway.

Objective To explore the characteristics of vaginal microecology and vaginitis distribution of female patients in Xi'an,so as to provide reliable reference for clinical treatment.Methods A total of 102 124 women in Shaanxi Provincial People's Hospital from January 2018 to August 2023 were selected as the research objects.Vaginal secretions were collected from patients,and the vaginal microecology was detected and analyzed.Results Among 102 124 female patients,99.87%had vaginal microecological imbalance.The main disease types were vulvovaginal candidiasis(VVC),accounting for 16.03%,bacterial vaginitis(BV),accounting for 9.61%and trichomonal vaginitis(TV),accounting for 1.34%.Statistical analysis showed that the age of VVC,BV and TV patients was mainly 21～30 years old.The prevalence of VVC and BV in summer and autumn was higher than that in other seasons,while the prevalence of TV was relatively high in summer.In addition,there were 27 552 cases of simple vaginitis(26.98%)and 1 443 cases of mixed vaginitis(1.41%)in 101 995 female patients with vaginal microecology imbalance.In patients with mixed vaginitis,the BV+VVC combination accounted for the vast majority(79.00%),and the age group was mainly between 21 and 40 years old.Among the 28 995 patients with vaginitis,4 308 patients(14.86%)had recurrence,and the recurrence rate of simple vaginitis(11.44%,3 152/27 552)was much lower than that of mixed vaginitis(80.11%,1 156/1 443).Conclusion The main type of female simple vaginitis in Xi'an is VVC,which has a high prevalence in summer and autumn.The main type of mixed vaginitis is BV+VVC,Compared with simple vaginitis,patients with mixed infection are more likely to relapse.

This article was aimed to study the preparation process of glycyrrhetinic acid (GA)-tanshinone IIA (TSN)-salvianolic acid B (SalB) compound liposomes with 3-succinic-30-stearyl glycyrrhetinic acid (18-GA-Suc) which is one of amphiphilicglycyrrhetinic acid derivatives as targeting molecule. The structure of the targeting molecule was validated by 1H-NMR and 13C-NMR methods. The feed ratio of 18-GA-Suc was optimized through single factor test and the incorporation ratio of 18-GA-Suc was determined by low-speed centrifugation. Meanwhile, physicochemi-cal properties between Suc-GTS-Lip and GTS-Lip were compared. In vitro release studies of three components in Suc-GTS-Lip were conducted by equilibrium dialysis method. The results showed that the optimum conditions were when the feed ratio of 18-GA-Suc was 10%lipid liposomal membrane (mol·mol-1). It revealed that the incorpora-tion ratio of 18-GA-Suc was 96.58%, and the encapsulation efficiencies of GA, TSN, and SalB were about 86.15%, 81.70%, and 91.05%, respectively. In addition, the Suc-GTS-Lip was spherical and uniformly dispersed with parti-cle size of 128.7 nm and zeta potential of-15.5 mV. The release model of GA and TSN was fitted well with Higuchi equation, while SalB was fitted well with Hixon-crowell equation. It was concluded that Glycyrrhetinic acid deriva-tives (18-GA-Suc) can be successfully expressed in the liposome membrane, and the optimal preparation method of Suc-GTS-Lip was stable. All three components encapsulated into liposomes had sustained-release effects, which laid a good foundation for its further study about liver-targeting.