Metabolic associated fatty liver disease (MAFLD) is fundamentally driven by an imbalance in hepatic fatty-acid flux: the influx of fatty acids exceeds the liver’s capacity for disposal, resulting in excessive hepatic lipid accumulation, predominantly in the form of triglycerides (TGs). The occurrence and progression of MAFLD depend on disordered regulation across multiple metabolic steps, including fatty-acid uptake, de novo lipogenesis (DNL), fatty-acid oxidation (FAO), and very low-density lipoprotein (VLDL) export. Forkhead box protein O1 (FOXO1) is a key transcriptional regulator within the hepatic network coordinating glucose and lipid metabolism. Under metabolic stress and insulin resistance (IR), FOXO1 expression is frequently increased, whereas its inhibitory phosphorylation is reduced. These changes enhance FOXO1 nuclear localization and transcriptional activity, thereby reprogramming the expression of genes related to metabolism in the liver. Because hepatic lipid deposition is the central pathological feature of MAFLD, the functional status of FOXO1 directly influences hepatic lipid homeostasis. Growing evidence suggests that FOXO1 can exert bidirectional, environment-dependent effects on hepatic lipid accumulation; however, the molecular basis for this functional switch remains incompletely understood. This review systematically summarizes the biological functions and regulatory mechanisms of FOXO1 and its roles in hepatic lipid metabolism, with a particular focus on its crosstalk with insulin signaling. FOXO1 expression is shaped by RNA modifications and epigenetic regulation mediated by non-coding RNAs. Its transcriptional output is precisely governed by post-translational modifications—such as phosphorylation and acetylation—as well as by coordinated nucleocytoplasmic shuttling. Notably, these regulatory patterns vary markedly across nutritional states, degrees of insulin resistance, and stages of disease. In the fed state, insulin/IGF-1 signaling activates the PI3K-AKT pathway, promoting the inhibitory phosphorylation of FOXO1 and facilitating additional modifications, including acetylation, methylation, and ubiquitination. Together, these events drive FOXO1 export from the nucleus and dampen its transcriptional activity, suppressing gluconeogenesis and constraining lipogenic programs. Conversely, during fasting or when insulin signaling is weakened, FOXO1 inhibition is relieved. FOXO1 accumulates in the nucleus, binds to DNA, and regulates the transcription of downstream target genes. Mechanistically, FOXO1 can aggravate hepatic lipid accumulation by activating genes involved in TG synthesis while repressing FAO-related pathways, thereby favoring storage over oxidation. However, under specific conditions, FOXO1 may also alleviate the hepatic lipid burden by promoting TG hydrolysis and enhancing VLDL secretion, thereby reducing the net hepatic lipid load. In addition, lipotoxic signals mediated by ceramides and diacylglycerols (Cer/DAG) activate atypical protein kinase C (aPKC), further exacerbating the disruption of the AKT-FOXO1 axis. This vicious cycle ultimately produces a metabolic paradox in which increased hepatic glucose output coexists with persistent, insulin-independent lipogenesis, accelerating MAFLD progression. Importantly, FOXO1 regulation is not uniform: during early metabolic overload, insulin-mediated suppression may remain effective, whereas in advanced insulin resistance, the loss of AKT control permits sustained FOXO1 activity. Such stage-dependent dynamics may help explain why FOXO1 can either promote steatosis or, in certain contexts, support programs that facilitate lipid turnover. Accordingly, interventions should be liver-specific and tuned to the disease stage, aiming to curb maladaptive FOXO1 signaling while preserving its capacity to promote triglyceride hydrolysis and VLDL secretion when advantageous. Overall, this review offers an important perspective on MAFLD pathogenesis, emphasizing FOXO1 as a potential therapeutic target and providing a theoretical basis for developing liver-specific, disease-course-dependent precision interventions.

Objective To explore the effectiveness of the generative large language model MedGo in nursing decision-making for elderly patients with multimorbidity. Methods A quasi-randomized controlled trial study was conducted involving 6 junior nurses, 6 senior nurses and the MedGo model from January 1, 2025 to March 31, 2025 at the Emergency Internal Medicine Ward of Shanghai East Hospital Affiliated to Tongji University. Clinical data of 120 elderly patients with multimorbidity were analyzed to compare the performance of the three groups in four tasks (nursing diagnosis assessment, nursing intervention formulation, complication identification, and complication prevention) from three evaluation dimensions: decision-making time consumption, decision accuracy, and decision-making quality. Results In terms of decision-making time, the senior nurse group completed all four tasks faster than the junior nurse group (P＜0.01), and the MedGo group completed all four tasks faster than the junior nurse group (P＜0.001) and the senior nurse group (P＜0.001). In terms of decision-making accuracy, senior nurse group scored higher than junior nurse group in all four tasks (P＜0.001), while the MedGo group outperformed the senior nurse group only in complication identification (P＜0.001). In terms of decision-making quality, the MedGo group scored higher than junior nurse group (P＜0.001) and senior nurse group (P＜0.001) in all four tasks. Conclusions The MedGo model demonstrates advantages of high efficiency, accuracy, and quality in nursing decision-making for elderly patients with multimorbidity; senior nurses outperform junior nurses in decision-making, providing diverse references for clinical nursing decision-making.

BACKGROUND:Bone tissue loss caused by tumors and trauma can have an adverse effect on postoperative rehabilitation.Therefore,scaffold materials are usually implanted during treatment.However,the existing implant materials are relatively simple and lack antibacterial properties.Early implantation may lead to iatrogenic autoinfection and have an adverse effect on osteogenesis.OBJECTIVE:To construct a KR-12-a5 polypeptide-nanohydroxyapatite-small intestinal submucosa composite scaffold and evaluate its feasibility as a material for promoting bone defect repair.METHODS:The small intestinal submucosa scaffold and the small intestinal submucosa scaffold containing 25,50,and 100 mg/mL nanohydroxyapatite(referred to as nHA-SIS scaffold)were prepared by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride/N-hydroxysuccinimide cross-linking method.The appropriate scaffold was screened for subsequent experiments by mechanical property testing.The antibacterial properties of KR-12-a5 polypeptide solution against Staphylococcus aureus,Streptococcus gordonii,and Fusobacterium nucleatum were detected.The nHA-SIS scaffolds were immersed in 250,500,and 1 000 μg/mL KR-12-a5 peptide solutions for 24 hours,and then freeze-dried to obtain peptide-loaded nanohydroxyapatite-porcine small intestinal submucosa composite scaffolds(denoted as P-nHA-SIS scaffolds).The sustained-release properties of the three groups of scaffolds were characterized.The nHA-SIS scaffolds and the three groups of P-nHA-SIS scaffolds were co-cultured with Staphylococcus aureus,Streptococcus gordonii,and Fusobacterium nucleatum for 24 hours or 48 hours.The scaffolds with strong antibacterial ability were screened by live and dead bacteria staining and scanning electron microscopy for subsequent experiments.The degradation properties and water absorption rates of the uncross-linked small intestinal submucosa scaffolds,cross-linked small intestinal submucosa scaffolds,nHA-SIS scaffolds,and P-nHA-SIS scaffolds were characterized.The extracts of cross-linked small intestinal submucosal scaffolds,nHA-SIS scaffolds,and P-nHA-SIS scaffolds were co-cultured with MC3T3-E1 cells.CCK-8 assay and live-dead cell staining were performed.The effects of the extracts of the three scaffolds on the migration of MC3T3-E1 cells were detected by Transwell chamber assay.RESULTS AND CONCLUSION:(1)The elastic modulus and compressive strength of 25,50,and 100 mg/mL nHA-SIS scaffolds were higher than those of small intestinal submucosal scaffolds(P＜0.05),among which the elastic modulus and compressive strength of 25 mg/mL nHA-SIS scaffolds were the highest,and this group of scaffolds were selected for subsequent experiments to load peptides.(2)KR-12-a5 peptide had strong antibacterial activity against common bacteria in bone defects(Staphylococcus aureus,Streptococcus gordonii,and Fusobacterium nucleatum).The three groups of P-nHA-SIS scaffolds all had sustained release properties.With the increase of peptide mass concentration,the antibacterial property of P-nHA-SIS scaffold was enhanced.Among them,the P-nHA-SIS scaffold loaded with 500 μg/mL peptide had achieved a satisfactory antibacterial effect,and this group of scaffolds would be selected in the future.(3)The degradation rate of the three groups of cross-linked scaffolds was lower than that of the uncross-linked scaffolds,and the water absorption rate was greater than that of the uncross-linked scaffolds.P-nHA-SIS scaffolds could promote the proliferation and migration of MC3T3-E1 cells without affecting the activity of MC3T3-E1 cells.(4)The results show that P-nHA-SIS scaffolds have strong antibacterial properties and the ability to promote the proliferation and migration of MC3T3-E1 cells,and are expected to be used in bone defect repair.

BACKGROUND:Bone tissue loss caused by tumors and trauma can have an adverse effect on postoperative rehabilitation.Therefore,scaffold materials are usually implanted during treatment.However,the existing implant materials are relatively simple and lack antibacterial properties.Early implantation may lead to iatrogenic autoinfection and have an adverse effect on osteogenesis.OBJECTIVE:To construct a KR-12-a5 polypeptide-nanohydroxyapatite-small intestinal submucosa composite scaffold and evaluate its feasibility as a material for promoting bone defect repair.METHODS:The small intestinal submucosa scaffold and the small intestinal submucosa scaffold containing 25,50,and 100 mg/mL nanohydroxyapatite(referred to as nHA-SIS scaffold)were prepared by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride/N-hydroxysuccinimide cross-linking method.The appropriate scaffold was screened for subsequent experiments by mechanical property testing.The antibacterial properties of KR-12-a5 polypeptide solution against Staphylococcus aureus,Streptococcus gordonii,and Fusobacterium nucleatum were detected.The nHA-SIS scaffolds were immersed in 250,500,and 1 000 μg/mL KR-12-a5 peptide solutions for 24 hours,and then freeze-dried to obtain peptide-loaded nanohydroxyapatite-porcine small intestinal submucosa composite scaffolds(denoted as P-nHA-SIS scaffolds).The sustained-release properties of the three groups of scaffolds were characterized.The nHA-SIS scaffolds and the three groups of P-nHA-SIS scaffolds were co-cultured with Staphylococcus aureus,Streptococcus gordonii,and Fusobacterium nucleatum for 24 hours or 48 hours.The scaffolds with strong antibacterial ability were screened by live and dead bacteria staining and scanning electron microscopy for subsequent experiments.The degradation properties and water absorption rates of the uncross-linked small intestinal submucosa scaffolds,cross-linked small intestinal submucosa scaffolds,nHA-SIS scaffolds,and P-nHA-SIS scaffolds were characterized.The extracts of cross-linked small intestinal submucosal scaffolds,nHA-SIS scaffolds,and P-nHA-SIS scaffolds were co-cultured with MC3T3-E1 cells.CCK-8 assay and live-dead cell staining were performed.The effects of the extracts of the three scaffolds on the migration of MC3T3-E1 cells were detected by Transwell chamber assay.RESULTS AND CONCLUSION:(1)The elastic modulus and compressive strength of 25,50,and 100 mg/mL nHA-SIS scaffolds were higher than those of small intestinal submucosal scaffolds(P＜0.05),among which the elastic modulus and compressive strength of 25 mg/mL nHA-SIS scaffolds were the highest,and this group of scaffolds were selected for subsequent experiments to load peptides.(2)KR-12-a5 peptide had strong antibacterial activity against common bacteria in bone defects(Staphylococcus aureus,Streptococcus gordonii,and Fusobacterium nucleatum).The three groups of P-nHA-SIS scaffolds all had sustained release properties.With the increase of peptide mass concentration,the antibacterial property of P-nHA-SIS scaffold was enhanced.Among them,the P-nHA-SIS scaffold loaded with 500 μg/mL peptide had achieved a satisfactory antibacterial effect,and this group of scaffolds would be selected in the future.(3)The degradation rate of the three groups of cross-linked scaffolds was lower than that of the uncross-linked scaffolds,and the water absorption rate was greater than that of the uncross-linked scaffolds.P-nHA-SIS scaffolds could promote the proliferation and migration of MC3T3-E1 cells without affecting the activity of MC3T3-E1 cells.(4)The results show that P-nHA-SIS scaffolds have strong antibacterial properties and the ability to promote the proliferation and migration of MC3T3-E1 cells,and are expected to be used in bone defect repair.

Background/Aims: Acetyl coenzyme A (acetyl-CoA) is one of the most essential metabolites in cell metabolism but its function and concentration in hepatocellular carcinoma (HCC) remain elusive and controversial. Methods: A comprehensive analysis of acetyl-CoA levels and acetyl-CoA synthetase 2 (ACSS2) expression across a range of samples, including patient specimens from both hepatitis B virus (HBV) positive and HBV negative HCC individuals, HBV-transgenic mouse HCC models, and multiple cell lines. Furthermore, to evaluate the functional significance of ACSS2 in HBV-related HCC, we implemented both genetic and pharmacological inhibition strategies targeting ACSS2. Molecular mechanism and mitophagy assessment were revealed by cleavage under target and tagmentation sequencing, RNA sequencing, bioinformatic analyses, transmission electron microscopy and JC-1 staining. Results: Our study revealed a distinct metabolic signature of HBV-related HCC, marked by elevated acetyl-CoA, which was driven by ACSS2. ACSS2 was upregulated by the carbohydrate response element-binding protein in HBV-related HCC. Furthermore, ACSS2 improved tumor cell proliferation, an effect that was dependent on its enzymatic activity. Mechanistically, ACSS2-induced acetyl-CoA accumulation activated voltage-dependent anion channels 1 transcription through increased H3K27ac occupancy, which subsequently promoted mitophagy and HBV-related HCC tumorigenesis. Notably, targeting ACSS2 by depletion or inhibition with a catalytic inhibitor significantly suppressed tumor growth. Conclusions These findings not only illustrate the interplay between metabolic reprogramming, epigenetic modification, and tumorigenesis in the context of HBV infection, but also highlight ACSS2 as a novel metabolic vulnerability in HBV-related HCC. Therefore, targeting ACSS2 could be a novel strategy against HBV-related HCC.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

This study explored the drying kinetics of Salviae Miltiorrhizae Radix et Rhizoma(SM), established the suitable models simulating the drying kinetics, and then analyzed the dynamic changes of active components during the drying processes with different methods, aiming to provide a basis for the establishment of suitable drying methods and the quality control of SM. The drying kinetics were studied based on the drying curve, drying rate, moisture effective diffusion coefficient, and drying activation energy, and the appropriate drying kinetics model of SM was established. The drying performance of different methods, such as hot air drying, infrared drying, and microwave drying of SM was evaluated, and the changes in the content of 10 salvianolic acids and 6 tanshinones during drying were analyzed by UPLC-TQ-MS. The Technique for Order Preference by Similarity to an Ideal Solution(TOPSIS) was employed to evaluate the quality of SM dried with different methods. The results showed that the drying rate and moisture effective diffusion coefficient of SM increased with the rise in drying temperature, and the maximum drying rates of different methods were in the order of microwave drying > infrared drying > hot air drying, slice > whole root. The drying rate decreased with the rise in temperature and the extension of drying time. The activation energy of hot air drying was higher than that of infrared drying in SM. The most suitable model for simulating the drying process of SM was the Page model. The TOPSIS results suggested infrared drying at 50 ℃ was the optimal drying method for SM. During the drying process, the content of salvianolic acids increased in different degrees with the loss of moisture, among which salvianolic acid B showed the largest increase of 44 times compared with that in the fresh medicinal material. Tanshinones also existed in the fresh herb of SM, and the content of tanshinone Ⅱ_A increased by 3 times after drying. The results provided a basis for the establishment of suitable drying methods and the quality control of SM.
Salvia miltiorrhiza/chemistry* ; Desiccation/methods* ; Drugs, Chinese Herbal/chemistry* ; Rhizome/chemistry* ; Kinetics ; Quality Control ; Abietanes

Asthma is a chronic inflammatory disease involving multiple inflammatory cells and cytokines. Its pathogenesis is complex, involving various cells and cytokines. Traditional Chinese medicine(TCM) theory suggests that the pathogenesis of asthma is closely related to the dysfunction of internal organs such as the lungs, spleen, and kidneys. In contrast, modern immunological studies have revealed the central role of T helper 1(Th1)/T helper 2(Th2) and T helper 17(Th17)/regulatory T(Treg) cellular immune imbalance in the pathogenesis of asthma. Th1/Th2 imbalance is manifested as hyperfunction of Th2 cells, which promotes the synthesis of immunoglobulin E(IgE) and the activation of eosinophil granulocytes, leading to airway hyperresponsiveness and inflammation.Meanwhile, Th17/Treg imbalance exacerbates the inflammatory response in the airways, further contributing to asthma pathology.Currently, therapeutic strategies for asthma are actively exploring potential targets for regulating the balance of Th1/Th2 and Th17/Treg immune responses. These targets include cytokines, transcription factors, key proteins, and non-coding RNAs. Precisely regulating the expression and function of these targets can effectively modulate the activation and differentiation of immune cells. In recent years,traditional Chinese medicine active ingredients have shown unique potential and prospects in the field of asthma treatment. Based on this, the present study systematically summarizes the efficacy and specific mechanisms of TCM active ingredients in treating asthma by regulating Th1/Th2 and Th17/Treg immune balance through literature review and analysis. These active ingredients, including flavonoids, terpenoids, polysaccharides, alkaloids, and phenolic acids, exert their effects through various mechanisms, such as inhibiting the activation of inflammatory cells, reducing the release of cytokines, and promoting the normal differentiation of immune cells. This study aims to provide a solid foundation for the widespread application and in-depth development of TCM in asthma treatment and to offer new ideas for clinical research and drug development of asthma.
Asthma/genetics* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Th2 Cells/drug effects* ; Th17 Cells/drug effects* ; T-Lymphocytes, Regulatory/drug effects* ; Th1 Cells/drug effects* ; Animals ; Cytokines/immunology* ; Medicine, Chinese Traditional

The chemical constituents were systematically separated from the roots of Berberis polyantha by various chromatographic methods, including silica gel column chromatography, HP20 column chromatography, polyamide column chromatography, reversed-phase C_(18) column chromatography, and preparative high-performance liquid chromatography. The structures of the compounds were identified by physicochemical properties and spectroscopic techniques(1D NMR, 2D NMR, UV, MS, and CD). Four phenylpropanoids were isolated from the methanol extract of the roots of B. polyantha, and they were identified as(2R)-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone-O-β-D-glucopyranoside(1), methyl 4-hydroxy-3,5-dimethoxybenzoate(2),(+)-syringaresinol(3), and syringaresinol-4-O-β-D-glucopyranoside(4). Compound 1 was a new compound, and other compounds were isolated from this plant for the first time. The anti-inflammatory activity of these compounds was evaluated based on the release of nitric oxide(NO) in the culture of lipopolysaccharide(LPS)-induced RAW264.7 macrophages. At a concentration of 10 μmol·L~(-1), all the four compounds inhibited the LPS-induced release of NO in RAW264.7 cells, demonstrating potential anti-inflammatory properties.
Plant Roots/chemistry* ; Animals ; Mice ; Berberis/chemistry* ; RAW 264.7 Cells ; Macrophages/immunology* ; Drugs, Chinese Herbal/isolation & purification* ; Nitric Oxide/metabolism* ; Molecular Structure ; Anti-Inflammatory Agents/isolation & purification*