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Background Inflammasomes have been found to interact with the gut microbiota, and this effect is associated with depression, but the mechanisms underlying this interaction have not been elucidated in detail. Results The locomotor activity of NLRP3 KO mice was significantly greater than that of their WT littermates, while cohousing and transplantation of the NLRP3 KO gut microbiota avoid the effects of NLRP3 KO on the general locomotor activity at baseline. Meanwhile, transplantation of the NLRP3 KO microbiota alleviated the CUS-induced depressive-like behaviors. The compositions of the gut microbiota in NLRP3 KO mice and WT mice were significantly different in terms of the relative abundance of Firmicutes , Proteobacteria , and Bacteroidetes . Fecal microbiota transplantation (FMT) from NLRP3 KO mice significantly ameliorated the depressive-like behavior induced by chronic unpredictable stress (CUS) in recipient mice. Given the correlation between circular RNA HIPK2 (circHIPK2) and depression and the observation that the level of circHIPK2 expression was significantly increased in CUS-treated mice compared with that in the control group, further experiments were performed. FMT significantly ameliorated astrocyte dysfunction in recipient mice treated with CUS via inhibition of circHIPK2 expression. Conclusions Our study illustrates the involvement of the gut microbiota-circHIPK2-astrocyte axis in depression, providing translational evidence that transplantation of the gut microbiota from NLRP3 KO mice may serve as a novel therapeutic strategy for depression.

Background Iron metabolism may be involved in the pathogenesis of the non-alcoholic fatty liver disease (NAFLD). The relationship between iron metabolism and NAFLD has not been clearly established. This study aimed to clarify the relationship between biomarkers of iron metabolism and NAFLD. Methods Based on the National Health and Nutrition Examination Survey (NHANES), restricted cubic spline models and multivariable logistic regression were used to examine the association between iron metabolism [serum iron (SI), serum ferritin (SF), transferrin saturation (TSAT), and soluble transferrin receptor (sTfR)] and the risk for NAFLD. In addition, stratified subgroup analysis was performed for the association between TSAT and NAFLD. Moreover, serum TSAT levels were determined in male mice with NAFLD. The expression of hepcidin and ferroportin, vital regulators of iron metabolism, were analyzed in the livers of mice by quantitative real-time PCR (qRT-PCR) and patients with NAFLD by microarray collected from the GEO data repository. Results Patients with NAFLD showed decreased SI, SF, and TSAT levels and increased STfR levels based on the NHANES. After adjusting for confounding factors, TSAT was significantly negatively correlated with NAFLD. Of note, the relationship between TSAT and NAFLD differed in the four subgroups of age, sex, race, and BMI ( P for interaction < 0.05). Consistently, mice with NAFLD exhibited decreased serum TSAT levels. Decreased hepcidin and increased ferroportin gene expression were observed in the livers of patients and mice with NAFLD. Conclusion Serum TSAT levels and hepatic hepcidin expression were decreased in both patients and mice with NAFLD. Among multiple biomarkers of iron metabolism, lower TSAT levels were significantly associated with a higher risk of NAFLD in the U.S. general population. These findings might provide new ideas for the prediction, diagnosis, and mechanistic exploration of NAFLD.

While acute ischemic stroke (AIS) and rhabdomyolysis (RML) have been reported to co-occur, their clinical relationship and associated outcomes remain poorly understood. This study aimed to investigate the clinical characteristics and outcomes of patients with concurrent AIS and RML. A retrospective analysis was conducted on patients admitted to the Department of Neurology from January 2014 to December 2023. The clinical and laboratory indicators, as well as the prognosis at discharge, were assessed. Among 9,360 AIS patients, 146 with RML (CK > 1,000 U/L) were assigned to the RML group, while 146 without RML formed the control group. Patients with RML had a higher incidence of comorbidities and acute complications, including diabetes (43.15% 26.03%, = 0.002), coronary heart disease (22.60% 10.96%, = 0.008), and acute kidney injury (35.36% 5.48%, < 0.001). Poor outcome (death or discharge against medical advice, DAMA) was significantly higher in the RML group than in controls (28.77% 3.42%, < 0.001). Multivariable logistic regression identified NIHSS score > 15 (OR = 4.932, 95% CI [1.902-12.794], = 0.001), infection (OR = 5.897, 95% CI [1.550-30.112], = 0.033), and elevated troponin I (>0.03 ng/ml; OR = 3.384, 95% CI [1.185-9.664], = 0.023) as independent predictors of poor outcomes. However, RML itself was not an independent predictor. AIS patients with RML exhibited an increased poor outcome rate. While multivariable analysis identified NIHSS score >15, infection, and elevated troponin I as independent predictors, RML was not an independent risk factor. Given the observational design and the co-occurrence with severity markers, these associations should not be interpreted as independent effects of RML. These findings pertain to in-hospital outcomes only. Post-discharge functional endpoints ( , 90-day modified Rankin Scale) were not available.

For hemodialysis patients at high risk of bleeding, a regional anticoagulant can be used, such as citrate or nafamostat mesylate (NM). The objective of this study was to evaluate NM as an alternative to citrate for anticoagulation in hemodialysis patients at high risk of bleeding. This retrospective single-center study included consecutive patients in our dialysis center treated with either citrate or NM anticoagulation for hemodialysis from January 2022 to December 2023.The primary outcome was major clotting, defined as premature dialysis due to extracorporeal circuit clotting. The secondary outcome was the incidence of a major bleeding episode during or after hemodialysis. In total, 651hemodialysis sessions were performed in 196 patients and were compared (289 citrate and 362 NM anticoagulation). A lower number of premature dialysis due to clotting occurred in the NM sessions compared to citrate sessions (0.84% vs.5.19%,  = 0.001). NM was associated with a lower risk of major clotting compared with citrate during treatment (OR:0.063; CI: 0.008-0.475;  = 0.007). Regarding second outcome, no more major bleeding events related to NM occurred compared to citrate. Among hemodialysis patients with high risk of bleeding, anticoagulation with NM, compared with citrate anticoagulation, provided relatively better efficacy, with no bleeding increment. NM is a valid alternative to citrate for hemodialysis patients at high risk of bleeding.

Chronic liver disease is rising in western countries and liver cirrhosis is the 12th leading cause of death worldwide. Simultaneously, use of gastric acid suppressive medications is increasing. Here, we show that proton pump inhibitors promote progression of alcoholic liver disease, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis in mice by increasing numbers of intestinal Enterococcus spp. Translocating enterococci lead to hepatic inflammation and hepatocyte death. Expansion of intestinal Enterococcus faecalis is sufficient to exacerbate ethanol-induced liver disease in mice. Proton pump inhibitor use increases the risk of developing alcoholic liver disease among alcohol-dependent patients. Reduction of gastric acid secretion therefore appears to promote overgrowth of intestinal Enterococcus , which promotes liver disease, based on data from mouse models and humans. Recent increases in the use of gastric acid-suppressive medications might contribute to the increasing incidence of chronic liver disease. Proton pump inhibitors (PPIs) reduce gastric acid secretion and modulate gut microbiota composition. Here Llorente et al . show that PPIs induce bacterial overgrowth of enterococci, which, in turn, exacerbate ethanol-induced liver disease both in mice and humans.

Background Atherosclerosis, a chronic multi-factorial vascular disease, has become a predominant cause of a variety of cardiovascular disorders. miR-26a was previously reported to be involved in atherosclerosis progression. However, the underlying mechanism of miR-26a in atherosclerosis remains to be further explained. Methods High-fat diet (HFD)-fed apolipoprotein E (apoE) −/− mice and oxidized low-density lipoprotein (ox-LDL)-stimulated human aortic endothelial cells (HAECs) were established as in vivo and in vitro models of atherosclerosis. RT-qPCR and western blot analysis were performed to measure the expression of miR-26a and transient receptor potential canonical 3 (TRPC3), respectively. Binding between miR-26a and TRPC3 was predicted with bioinformatics software and verified using a dual luciferase reporter assay. The effects of miR-26a on the lipid accumulation, atherosclerotic lesion, and inflammatory response in HFD-fed apoE −/− mice were investigated by a colorimetric enzymatic assay system, hematoxylin–eosin and oil-Red-O staining, and ELISA, respectively. Additionally, the effects of miR-26a or combined with TRPC3 on cell viability, apoptosis and the nuclear factor-kappa B (NF-κB) pathway in ox-LDL-stimulated HAECs were evaluated by MTT assay, TUNEL assay, and western blot, respectively. Results miR-26a was downregulated in HFD-fed apoE −/− mice and ox-LDL-stimulated HAECs. miR-26a overexpression inhibited the pathogenesis of atherosclerosis by attenuating hyperlipidemia, atherosclerotic lesion and suppressing inflammatory response in HFD-fed apoE −/− mice. Moreover, miR-26a overexpression suppressed inflammatory response and the NF-κB pathway, promoted cell viability and inhibited apoptosis in ox-LDL-stimulated HAECs. Additionally, TRPC3 was demonstrated to be a direct target of miR-26a. Enforced expression of TRPC3 reversed the effects of miR-26a on cell viability, apoptosis, and the NF-κB pathway in ox-LDL-treated HAECs. Conclusions miR-26a alleviated the development of atherosclerosis by regulating TRPC3, providing a potential target for atherosclerosis treatment.

Septic associated acute kidney injury (SA-AKI) is common in the critically ill. Inadequate renal medullary tissue oxygenation has been linked to its pathogenesis. The aim of this preliminary study was to assess the feasibility of intermittent PuO monitoring using a blood gas analyzer in sepsis patients; to explore the effectiveness of time-weighted average PuO (PuO ) for predicting SA-AKI. A total of 76 consecutive adult patients who were admitted to our intensive care unit (ICU) from September 2023 to March 2024 were prospectively recruited. PuO was measured with a blood gas analyzer at 0h, 3h, and 6h after ICU admission. PuO was determined by the sum of the mean PuO values among consecutive time points multiplied by the period of time between consecutive time points and then dividing by the total time. All patients were followed throughout the ICU stay, and the development of SA-AKI during 48 h was evaluated. Approximately 23.68% developed AKI during the ICU stay. PuO was lower in patients who developed AKI. The ROC curve analysis revealed that lower PuO was associated with AKI development at the cutoff of <68 mmHg (area under the curve [AUC] 0.687;  = .008). In the logistic regression models, PuO lower than 68 mmHg was associated with the development of AKI, when adjusted by confounding factors (OR 8.20;  = .002). Measurement of PuO is feasible by collecting urine from a Foley catheter for analysis in a blood gas machine. 6h PuO had a significant independent predictive value for AKI.

Nonalcoholic fatty liver disease (NAFLD) is a global epidemic, and there is no standard and efficient therapy for it. Chitosan oligosaccharide (COS) is widely known to have various biological effects, and in this study we aimed to evaluate the liver-protective effect in diet-induced obese mice for an enzymatically digested product of COS called COS23 which is mainly composed of dimers and trimers. An integrated analysis of the lipidome and gut microbiome were performed to assess the effects of COS23 on lipids in plasma and the liver as well as on intestinal microbiota. Our results revealed that COS23 obviously attenuated hepatic steatosis and ameliorated liver injury in diet-induced obese mice. The hepatic toxic lipids—especially triglycerides (TGs) and free fatty acids (FFAs)—were decreased dramatically after COS23 treatment. COS23 regulated lipid-related pathways, especially inhibiting the expressions of FFA-synthesis-related genes and inflammation-related genes. Furthermore, COS23 could alter lipid profiles in plasma. More importantly, COS23 also decreased the abundance of Mucispirillum and increased the abundance of Coprococcus in gut microbiota and protected the intestinal barrier by up-regulating the expression of tight-junction-related genes. In conclusion, COS23, an enzymatically digested product of COS, might serve as a promising candidate in the clinical treatment of NAFLD.

Yunnanopilia longistaminata is a rare forest vegetable, distributed in Yunnan and Guangxi Provinces of southeastern China. It is characterized by a unique flavor and rich nutritional value, making it a potential resource for dietary and medicinal applications. However, the absence of a high quality reference genome has limited the comprehensive development and utilization of this valuable plant resource. In this study, we present the chromosome-level genome assembly of Y. longistaminata using Nanopore sequencing and Hi-C technology. Its genome size was approximately 871.46 Mb, with a contig N50 of 8.47 Mb. A total of 870.61 Mb (99.97%) of the assembled sequences were anchored to ten chromosomes with a complete BUSCO score of 95.66%. Genome annotation revealed 22,050 protein-coding genes and 677.72 Mb of repetitive sequences. Phylogenomic analysis revealed Y. longistaminata forms a distinct clade with Santalum , exhibiting 1,525 expanded and 4,962 contracted gene families, and underwent two paleopolyploidization events. This frst high-quality Y. longistaminata genome will serve as a fundamental basis for future studies on functional genomics and genome evolution.

Introduction Preservation of porcine semen is essential for artificial insemination and genetic improvement in pig breeding programs. However, the overproduction of reactive oxygen species (ROS) and lower levels of protein phosphorylation emerge as two challenges during semen preservation. Inspired by the innate ligand-receptor binding biofunction of dopamine, herein, a dual-task nano-protectant that combines ROS-scavenging and protein phosphorylation-regulating properties via incorporating the natural antioxidant epigallocatechin gallate (EGCG) into polydopamine nanoparticles (EGCG@PDA NPs) was proposed to enhance the quality of pig semen during storage at 4 ℃. The results suggested that EGCG@PDA NPs significantly maintained sperm motility, acrosome integrity and mitochondrial membrane potential, extending semen storage time from 3 days to 10 days. Furthermore, EGCG@PDA NPs effectively scavenged excess ROS and inhibited ROS-mediated sperm apoptosis through the extracellular regulated protein kinases (ERK) signaling pathway. Intriguingly, EGCG@PDA NPs could degrade into ultrasmall particles (< 10 nm) in the semen or H 2 O 2 systems. These particles could target and activate the dopamine D2 receptor (D2DR) on membrane surface of sperm midpiece, thereby enhancing protein phosphorylation via the downstream cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) signaling pathway, ultimately improving sperm motility parameters. This study presents a novel nano-strategy to boost the quality of pig semen, offering significant implications for the pig industry. Graphical Abstract