Background: Brucellosis is a chronic zoonotic disease, and Ningxia is one of the high prevalence regions in China. To mitigate the spread of brucellosis, the government of Ningxia has implemented a comprehensive prevention and control plan (2022-2024). It is meaningful to quantitatively evaluate the accessibility of this strategy.Methods: Based on the transmission characteristics of brucellosis in Ningxia, we propose a dynamical model of sheep-human-environment, which coupling with the stage structure of sheep and indirect environmental transmission. We first calculate the basic reproduction number $$R_0$$R0 and use the model to fit the data of human brucellosis. Then, three widely applied control strategies of brucellosis in Ningxia, that is, slaughtering of sicked sheep, health education to high risk practitioners, and immunization of adult sheep, are evaluated.Results: The basic reproduction number is calculated as $$R_{0}=1.47$$R0=1.47 , indicating that human brucellosis will persist. The model has a good alignment with the human brucellosis data. The quantitative accessibility evaluation results show that current brucellosis control strategy may not reach the goal on time. “Ningxia Brucellosis Prevention and Control Special Three-Year Action Implementation Plan (2022-2024)” will be achieved in 2024 when increasing slaughtering rate $$\gamma$$γ by 30 $$\%$$% , increasing health education to reduce $$\beta _{h}$$βh to 50 $$\%$$% , and an increase of immunization rate of adult sheep $$\theta$$θ by 40 $$\%$$% .Conclusion: The results demonstrate that the comprehensive control measures are the most effective for brucellosis control, and it is necessary to further strengthen the multi-sectoral joint mechanism and adopt integrated measures to prevention and control brucellosis. These results can provide a reliable quantitative basis for further optimizing the prevention and control strategy of brucellosis in Ningxia.

Background: Resveratrol is a potent phytochemical known for its potential in treating cardiometabolic multimorbidity. However, its underlying mechanisms remain unclear. Our study systematically investigates the effects of resveratrol on cardiometabolic multimorbidity and elucidates its mechanisms using network pharmacology and molecular docking techniques. Methods: We screened cardiometabolic multimorbidity-related targets using the OMIM, GeneCards, and DisGeNET databases, and utilized the DSigDB drug characterization database to predict resveratrol’s effects on cardiometabolic multimorbidity. Target identification for resveratrol was conducted using the TCMSP, SymMap, DrugBank, Swiss Target Prediction, CTD, and UniProt databases. SwissADME and ADMETlab 2.0 simulations were used to predict drug similarity and toxicity profiles of resveratrol. Protein–protein interaction (PPI) networks were constructed using Cytoscape 3.9.1 software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were performed via the DAVID online platform, and target-pathway networks were established. Molecular docking validated interactions between core targets and resveratrol, followed by molecular dynamics simulations on the optimal core proteins identified through docking. Differential analysis using the GEO dataset validated resveratrol as a core target in cardiometabolic multimorbidity. Results: A total of 585 cardiometabolic multimorbidity target genes were identified, and the predicted results indicated that the phytochemical resveratrol could be a major therapeutic agent for cardiometabolic multimorbidity. SwissADME simulations showed that resveratrol has potential drug-like activity with minimal toxicity. Additionally, 6703 targets of resveratrol were screened. GO and KEGG analyses revealed that the main biological processes involved included positive regulation of cell proliferation, positive regulation of gene expression, and response to estradiol. Significant pathways related to MAPK and PI3K-Akt signaling pathways were also identified. Molecular docking and molecular dynamics simulations demonstrated strong interactions between resveratrol and core targets such as MAPK and EGFR. Conclusions: This study predicts potential targets and pathways of resveratrol in treating cardiometabolic multimorbidity, offering a new research direction for understanding its molecular mechanisms. Additionally, it establishes a theoretical foundation for the clinical application of resveratrol.

Non‐alcoholic fatty liver disease (NAFLD) and diabetes mellitus (DM) are prevalent metabolic disorders that frequently coexist, yet their shared molecular mechanisms remain poorly understood, and current therapies often yield suboptimal outcomes. Lycium barbarum L. ( Lycii fructus , LF), a traditional medicinal herb, has demonstrated clinical efficacy in treating both conditions, but its mechanism of action in comorbidity management remains unclear. Active LF compounds were identified via the TCMSP database, with potential targets predicted using Swiss Target Prediction and PharmMapper. Disease‐associated proteins for NAFLD and DM were curated from OMIM, GeneCards, DisGeNET, UniProt, DrugBank, and TTD. A protein–protein interaction (PPI) network was constructed from these targets, and GO and KEGG pathway analyses were performed using the DAVID platform. Key targets were further refined through network module analysis via Metascape. Drug‐likeness of bioactive compounds was assessed using SwissADME and ADMETlab 2.0. Molecular docking and dynamics simulations validated interactions between core targets and LF compounds. Mendelian randomization (MR) analysis tested causal relationships between core genes and disease phenotypes. We identified 58 shared therapeutic targets for NAFLD‐DM comorbidity, including HSP90AA1, ESR1, MMP9, EGFR, AKT1, and CASP3. GO analysis implicated LF in blood pressure regulation and glucose‐stimulated insulin secretion. KEGG pathways highlighted modulation of MAPK, PI3K‐Akt, FoxO, and mTOR signaling. 24‐methylenelanost‐8‐enol and cryptoxanthin monoepoxide emerged as core bioactive compounds with favorable drug‐likeness. Molecular docking confirmed strong binding of 24‐methylenelanost‐8‐enol to HSP90AA1 and cryptoxanthin monoepoxide to MMP9, further supported by dynamics simulations. MR analysis revealed a significant causal role for CASP3 in both NAFLD and DM, aligning with network pharmacology predictions. LF's therapeutic effects on NAFLD‐DM comorbidity likely arise from terpenoid and cryptoxanthin mediated modulation of apoptosis and inflammation pathway. This study identifies shared molecular networks, proposes candidate mechanisms for LF's efficacy, and provides a framework for targeting multifactorial metabolic diseases.

Ethnopharmacological Relevance: Coptis chinensis Franch. (Huanglian), a traditional Chinese medicinal herb used for “heat” and “dampness” syndromes, is clinically associated with metabolic disorders such as NAFLD. Berberine (BBR), its major bioactive alkaloid, has shown metabolic benefits, though its mechanistic basis in NAFLD remains unclear. Aim of the Study: To identify candidate pathways underlying the effects of BBR in NAFLD, a computational target prediction approach was employed, followed by in vivo experimental validation in a zebrafish model. Materials and Methods: A thioacetamide (TAA)-induced liver injury zebrafish model was established. Hepatic lipid accumulation and histopathology were assessed by Oil Red O staining, H&E staining, and qPCR. A computational target prediction approach was employed to identify potential BBR-NAFLD overlapping targets, followed by pathway enrichment analysis and molecular docking simulations to prioritize candidate pathways. Bile acid profiles were analyzed using UHPLC-MS/MS metabolomics. The predicted PPARγ pathway was experimentally validated using the specific antagonist GW9662 and the agonist rosiglitazone. Results: BBR significantly reduced hepatic steatosis and restored liver morphology. A total of 104 overlapping targets were identified, with PPAR signaling emerging as a key pathway. BBR showed stable binding to PPARγ (−7.92 kcal/mol). In vivo, BBR restored the expression of pparg, rxra, cyp7a1, cyp27a1, and cyp8b1, all of which were suppressed by TAA; these effects were reversed by GW9662, confirming PPARγ dependence. Metabolomics revealed reduced levels of 6-ketoLCA and UDCA-3S, which were partially reversed by PPARγ inhibition. Conclusion: BBR alleviates TAA-induced liver injury by regulating PPARγ and bile acid homeostasis, integrating systems pharmacology and experimental validation to support the ethnopharmacological use of C. chinensis in metabolic liver disease.

Background: Non-invasive therapies for heart failure represent one of the current major focuses in clinical research. Plant-derived extracellular vesicles (PEVs) have recently emerged as a promising therapeutic modality. Objectives: In this study, we investigated the therapeutic potential of PEVs in heart failure with preserved ejection fraction (HFpEF), focusing on extracellular vesicles derived from Lycium barbarum (Gq-EVs). Methods: We first obtained Gq-EVs with high biological activity and high concentration from Lycium barbarum juice and characterized them by using transmission electron microscopy, nanoparticle tracking analysis, and metabolite composition analysis. Results: Our in vivo findings indicate that nebulized inhalation of Gq-EVs for 7, 14, and 21 days improved abnormal cardiac diastolic function, reduced excessive myocardial hypertrophy, and attenuated inflammatory cell infiltration and collagen deposition in HFpEF mice. Further in vivo and in vitro experiments showed that Gq-EVs can reach injured cardiac tissue, improve mitochondrial function, and are associated with reduced cardiomyocyte apoptosis and amelioration of myocardial hypertrophy, potentially involving TP53-related apoptotic signaling. Conclusions: Overall, nebulized delivery of Gq-EVs may be a relatively non-invasive, well-tolerated, and cost-effective therapeutic strategy for HFpEF, highlighting the potential of PEV-based nanotherapies and offering a sustainable approach for the medical utilization of Lycium barbarum resources.

Non‐alcoholic fatty liver disease (NAFLD) is a common metabolic liver disorder with limited effective pharmacological treatments. Tetrandrine (Tet), a major bioactive alkaloid derived from Stephaniae Tetrandrae Radix , has shown anti‐inflammatory and metabolic regulatory potential. In this study, we systematically investigated the therapeutic effects and underlying mechanisms of STR alkaloids, with a focus on Tet in NAFLD. Network pharmacology identified active alkaloids and 194 overlapping targets associated with NAFLD, and protein–protein interaction analysis highlighted TP53, EGFR, STAT3, AKT1, and TNF as key hub genes. Functional enrichment analyses indicated that the PI3K/AKT, MAPK, and FoxO signaling pathways were significantly involved, with PI3K/AKT emerging as the central signaling pathway. Molecular docking and molecular dynamics simulations demonstrated stable binding interactions between Tet and STAT3 as well as TNF. Mendelian randomization analysis further suggested a causal relationship between elevated STAT3 expression and increased NAFLD risk. Experimental validation in a thioacetamide‐induced zebrafish NAFLD model showed that Tet significantly reduced hepatic lipid accumulation and decreased serum TG, TC, ALT, and AST levels. Mechanistically, Tet activated PI3K/AKT/STAT3 signaling while inhibiting TP53 and Bax. External validation using GEO datasets supported AKT1 and EGFR as important regulatory genes. Overall, these findings demonstrated that Tet ameliorates NAFLD by modulating lipid metabolism and apoptosis through activation of the PI3K/AKT/STAT3 signaling pathway, providing integrated computational, genetic, and experimental evidence for its potential as a therapeutic agent.