Staphylococcus aureus is a Gram-positive bacterium with strong pathogenicity. With the widespread use of antibiotics， its multi-drug resistance has gradually increased. Among them， methicillin-resistant S. aureus （MRSA） is one of the main pathogens of hospital and community infections. Antimicrobial peptides are short-chain peptides with good antibacterial effects and low drug resistance， which have been widely studied in recent years. This study summarizes the mechanism of action of antimicrobial peptides and related study on antimicrobial peptides against MRSA from different sources. It is found that the mechanisms of action of antimicrobial peptides include targeting bacterial cell membranes， bacterial cells， and bacterial cell walls， etc. Besides isolating antimicrobial peptides with anti-MRSA activity from animals， plants， and microorganisms， antimicrobial peptides can also be obtained through synthetic methods. Among them， GHa-derived peptides from animal sources， Ib-AMP4 from plant sources， Ph-SA from microbial sources， the synthetic peptide LLKLLLKLL-NH2， and so on， due to their effective antibacterial activity， rapid bactericidal speed， and low toxicity， are promising candidates for anti-MRSA drugs.

Ferroptosis of chondrocytes is a significant contributor to osteoarthritis (OA), for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis. Here, we screen for anti-ferroptotic drugs in Food and Drug Administration (FDA)-approved drug library via a high-throughput manner in chondrocytes. We identified a group of FDA-approved anti-ferroptotic drugs, among which vitamin K showed the most powerful protective effect. Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix (ECM) degradation in chondrocytes. Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus (DMM) mouse model. Mechanistically, transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6 (Gas6). Furthermore, exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase (AXL)/phosphatidylinositol 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) axis. Together, we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis, indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.

Liraglutide (Lira), a glucagon-like peptide-1 (GLP-1) receptor agonist approved for diabetes and obesity, has shown significant potential in treating metabolic dysfunction-associated steatotic liver disease (MASLD). However, its systematic molecular regulation and mechanisms remain underexplored. In this study, a mouse model of MASLD was developed using a high-fat diet (HFD), followed by Lira administration. Proteomics and glycoproteomics were analyzed using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS), while potential molecular target analysis was conducted via quantitative real-time polymerase chain reaction (qPCR) and Western blotting. Our results revealed that Lira treatment significantly reduced liver weight and serum markers, including alanine aminotransferase (ALT) and others, with glycosylation changes playing a more significant role than overall protein expression. The glycoproteome identified 255 independent glycosylation sites, emphasizing the impact of Lira on amino acid, carbohydrate metabolism, and ferroptosis. Simultaneously, proteomic analysis highlighted its effects on lipid metabolism and fibrosis pathways. 21 signature molecules, including 7 proteins and 14 N-glycosylation sites (N-glycosites), were identified as potential targets. A Lira hydrogel formulation (Lira@fibrin (Fib) Gel) was developed to extend drug dosing intervals, offering enhanced therapeutic efficacy in managing chronic metabolic diseases. Our study demonstrated the importance of glycosylation regulation in the therapeutic effects of Lira on MASLD, identifying potential molecular targets and advancing its clinical application for MASLD treatment.

BACKGROUND:Traditional methods of urinary tract reconstruction are limited by donor scarcity,high complication rates,and suboptimal functional recovery.Tissue engineering strategies offer new directions in this field.Since the urinary tract is mainly composed of muscle tissue,the key is to find suitable seed cells and efficiently induce them to differentiate into smooth muscle cells.Comparative studies on the efficacy of different smooth muscle cell induction regimens are still lacking. OBJECTIVE:To isolate,culture,and identify human urine-derived stem cells,and to compare the effects of two different induction protocols. METHODS:Human urine-derived stem cells were isolated from urine samples of 11 healthy adult volunteers by multiple centrifugations.Surface markers were identified by flow cytometry.The multi-directional differentiation potential of human urine-derived stem cells was verified through osteogenic and adipogenic differentiation.Differentiation was induced by transforming growth factor-β1 or transforming growth factor-β1 combined with platelet derived growth factor for 14 days.Immunofluorescence staining and western blot assay were employed to compare the expression differences of smooth muscle-specific proteins(α-SMA and SM22). RESULTS AND CONCLUSION:(1)Urine-derived stem cells were successfully isolated from the eight urine samples of healthy people.These cells exhibit a"rice grain"-like morphology and possess a robust proliferative capacity.(2)Urine-derived stem cells exhibited high expression of mesenchymal stem cell surface markers(CD73,CD90,and CD44)and extremely low expression of hematopoietic stem cell surface markers(CD34 and CD45).These cells did not express CD19,CD105,and HLA-DR.(3)After osteogenic and adipogenic differentiation,the formation of calcium nodules and lipid droplets was observed,with positive staining results from Alizarin Red S and Oil Red O staining.(4)After 14 days of smooth muscle induction culture,immunofluorescence staining revealed that the smooth muscle differentiation rate of urine-derived stem cells treated with a combination of transforming growth factor-β1 and platelet derived growth factor was significantly higher compared to those treated with transforming growth factor-β1 alone(P<0.005).(5)After 14 days of smooth muscle induction culture,western blot assay further demonstrated that the expression levels of α-SMA and SM22 in the transforming growth factor-β1/platelet derived growth factor group were significantly elevated compared to those in the transforming growth factor-β1 only group(P<0.005).These findings confirm that urine-derived stem cells can be non-invasively isolated using multiple rounds of centrifugation.Compared with transforming growth factor-β1 alone,the combination of transforming growth factor-β1 and platelet derived growth factor can improve the efficiency of inducing urine-derived stem cells to differentiate into smooth muscle cells.

The theory of " heart governing the exterior" derives from Prohibition of Pricking in Suwen, which has an important position in the clinical practice of traditional Chinese medicine. This article sorts out the interpretation of " heart governing the exterior" of physicians in the past dynasties, and summarizes the clinical application of " heart governing the exterior" in chest painful impediment, warm disease, dermatosis, allergic rhinitis, tic disorder, and diabetic neuropathy. It is found that the theory of " heart governing the exterior" is widely used in clinical practice and has good effects. This paper further expands and enhances its theoretical connotation, that is, the physiological and pathological connection and clinical application of the three dimensions of heart yang, heart blood, and heart spirit with the life and mental activities dominated by it, as well as the overall external performance. In addition, by exploring the relationship between " heart governing the exterior" and " brain-heart axis" , " brain-skin axis" in Western medicine, it indirectly confirms the rationality of " heart governing the exterior" in Western medicine, and lays the foundation for the further development and application of the theory of " heart governing the exterior" .

BackgroundNon-suicidal self-injury （NSSI） behavior among adolescents has become a global public health concern. Anxiety and depression are considered key factors influencing NSSI behavior， while social support may play a protective role in alleviating emotional and behavioral issues. However， existing research has primarily focused on the direct impact of individual factors on NSSI behavior， with insufficient exploration of the combined effects of anxiety， depression and social support. ObjectiveTo investigate the direct effect of anxiety on NSSI， the mediating role of depression and the moderating role of social support in relationship between anxiety and NSSI behavior， thus to provide references for the prevention and intervention of NSSI behavior among adolescents. MethodsIn February 2022， a total of 40 820 students in grades 7 to 12 across 10 middle schools in a district of Chengdu were selected as participants， and they were assessed using Generalized Anxiety Disorder Scale-7 item （GAD-7）， Patient's Health Questionnaire Depression Scale-9 item （PHQ-9）， Social Support Scale for Urban Students （SSSUS） and Adolescent Self-Harm Scale （ASHS）. Pearson correlation analysis was conducted to examine the correlations between scale scores among adolescents with NSSI behaviors. Mediation and moderation analyses were performed using Process 3.5 in SPSS， and the significance was tested with bootstrapping. The interaction was visualized by using simple slope analysis. ResultsAmong 34 534 （84.60%） valid respondents， 542 adolescents （1.57%） reported engaging in NSSI behavior. Significant differences in gender， GAD-7 scores， PHQ-9 scores， and SSSUS scores were observed between NSSI behavior group and non-NSSI group （χ²/t=62.889， 71.120， 94.365， -41.464， P<0.01）.Adolesents with NSSI showed positive correlations between GAD-7 scores and both ASHS and PHQ-9 scores （r=0.158， 0.166， P<0.01）. PHQ-9 scores were positively correlated with ASHS scores （r=0.364， P<0.01）， but negatively correlated with SSSUS scores （r=-0.290， P<0.01）. SSSUS scores were negatively correlated with ASHS scores （r=-0.247， P<0.01）. Depression partially mediated the relationship between anxiety and NSSI behavior， with an effect size of 0.544 （95% CI： 0.162~0.944）， accounting for 35.79% of the total effect. Social support moderated the relationship between depression and NSSI bahavior， with an effect value of -0.082 （95% CI： -0.135~-0.029）. ConclusionAnxiety not only directly influences NSSI bahavior among adolescents， also indirectly exacerbates it through depression， while social support mitigates the impact of depression on NSSI behavior. ［Funded by Youth Project of National Natural Science Foundation of China （number， 82401812）； Project of Health Commission of Sichuan Province （number， 24LCYJPT18）］

BackgroundThe distressingly high prevalence of depressive symptoms among adolescents exerts profound impacts on their physical and psychological development， urgently necessitating effective preventive interventions. Existing studies， however， have predominantly focused on isolated risk factors， neglecting to construct an integrated model that systematically disentangles the intricate relationships linking parenting styles， learning burnout， and childhood trauma to adolescent depressive symptoms. Moreover， the potential protective roles of social support and psychological resilience in this context remain insufficiently elucidated. ObjectiveTo construct a structural equation model encompassing multiple pathways to unravel the comprehensive mechanisms through which negative parenting styles， childhood trauma， learning burnout， psychological resilience， and social support collectively influence adolescent depressive symptoms， thereby providing evidence-based intervention strategies. MethodsA stratified sampling technique was utilized to recruit 5 865 students from 12 middle schools in Chengdu City， Sichuan Province from March to May 2022. Participants were assessed using the following validated instruments： the Short-form Egna Minnen av Barndoms Uppfostran （s-EMBU）， the Childhood Trauma Questionnaire-Short Form （CTQ-SF）， the Adolescent Student Burnout Inventory， the Patients' Health Questionnaire Depression Scale-9 item （PHQ-9）， the Social Support Rating Scale （SSRS），and the Connor-Davidson Resilience Scale （CD-RISC）. A partial least squares structural equation modeling （PLS-SEM） approach was employed to construct a predictive framework examining the complex network of pathways through which negative parenting styles， childhood trauma， learning burnout， psychological resilience，and social support collectively influence depressive symptoms in adolescents. ResultsThe PHQ-9 scores demonstrated significant positive correlations with the scores on s-EMBU overprotection subscale （r=0.272， P<0.01）， s-EMBU rejection subscale （r=0.368， P<0.01）， CTQ-SF （r=0.288， P<0.01） and Adolescent Student Burnout Inventory （r=0.587， P<0.01）. Conversely， significant negative correlations were observed between PHQ-9 scores and both SSRS （r=-0.532， P<0.01） and CD-RISC scores （r=-0.418， P<0.01）. Negative parenting styles （β=0.113， 95% CI： 0.087-0.138） and learning burnout （β=0.339， 95% CI： 0.315-0.364） emerged as significant positive predictors of depressive symptoms， with childhood trauma mediating the relationship between negative parenting styles and depressive symptoms （effect size=0.018， 95% CI： 0.013-0.024）. Social support servesed as a mediating pathway between negative parenting styles and depressive symptoms （β=0.080， 95% CI： 0.069-0.092）， as well as between negative parenting styles and childhood trauma （β=0.041， 95% CI： 0.032-0.050）. It also functioned as an intermediary pathway linking learning burnout to depressive symptoms （β=0.092， 95% CI： 0.081-0.104） and connecting learning burnout with childhood trauma （β=0.048， 95% CI： 0.037-0.058）. Additionally， psychological resilience serveed as a mediating pathway between negative parenting styles and depressive symptoms （β=0.004， 95% CI： 0.002-0.007）， between learning burnout and depressive symptoms （β=0.037， 95% CI： 0.023-0.052）， and between childhood trauma and depressive symptoms （β=0.003， 95% CI： 0.001-0.006）. ConclusionLearning burnout exerts a direct effect on adolescent depressive symptoms. Negative parenting styles influence depressive symptoms both directly and indirectly through childhood trauma. Furthermore， social support and psychological resilience serve as mediator linking negative parenting styles and learning burnout to depressive symptoms in adolescents. ［Funded by Science and Technology Project of the Health Commission of Sichuan Province （number， 24LCYJPT18）］

Mid-to-late stage ankle arthritis is a chronic degenerative disease that is extremely common in clinical practice.It is characterized by significant cartilage degeneration and subchondral bone sclerosis,accompanied by the formation of osteophytes around the joint,often leading to joint deformity.This condition causes severe pain in the patients during walking,severely restricts their activities,and affects their qualities of life.In recent years,with the continuous improvement of medical standards,the treatment methods for mid-to-late stage ankle arthritis have shown a diversified development trend.Non-surgical treatments primarily include activity restriction,orthotic devices,oral non-steroidal anti-inflammatory drugs(NSAIDs),and intra-articular injections of the talocrural joint.The surgical treatments primarily include joint distraction arthroplasty,periacetabular osteotomy,total ankle arthroplasty,and ankle arthrodesis.Tissue engineering therapy,as an emerging method,has also received considerable attention.This article systematically reviewed the selection principles and research progress of various treatment options for mid-to-late stage ankle arthritis,including traditional treatments,non-surgical treatments,surgical treatments,and tissue engineering treatments.By deeply analyzing the basic principles and advantages and disadvantages of each treatment method,and combining the latest research findings on clinical outcomes,a scientific and comprehensive clinical decision-making reference system was constructed to provide clearer and more comprehensive treatment choices for both doctors and patients,thereby effectively improving treatment outcomes and enhancing the quality of life for the patients.

Objective To investigate the protective effects of mitochondrial preconditioning in pericytes(PC)against pulmonary vascular leakage in septic rats.Methods ① 128 specific-pathogen-free SD rats(equal gender,200±20 g)were randomized into:Sham group(postoperative tail vein injection of 0.5 mL saline),Sepsis(Sep)group(CLP+saline),PC group(CLP+untreated PC:106 cells/rat),and Mito-PC group(CLP+PC preconditioned with 2 μg mitochondria/104 cells for 12 h).Assessments included:PC lung colonization(flow cytometry),pulmonary barrier function(Evans blue assay),lung histopathology(HE staining),serum organ injury markers[cTnT(cardiac),urea/creatinine(renal)],and inflammatory cytokines(TNF-α,IL-6).② MSC-derived mitochondria were validated by electron microscopy/flow cytometry;primary retinal PCs from weaned SD rats were purity-verified(confocal microscopy).In vitro groups:Control(PC),Mito-PC,PC+H2O2(0.5 μmol/L,4 h),and Mito-PC+H2O2.Antioxidant capacity was assessed via pentose phosphate pathway(PPP)activity,NADPH levels,G6PD activity,and NADP+/NADPH ratio.Results① Compared with Sham,Sep group showed significant increase in pulmonary leakage(Evans blue P<0.05),severe lung injury,elevated serum markers(TNF-α,IL-6,cTnT,urea,creatinine all P<0.05),0％72 h survival.PC group showed partial improvement(P<0.05).Mito-PC group demonstrated significant reduction in vascular leakage(P<0.05 vs PC group),improved histopathology and organ function(P<0.05),attenuated inflammation(P<0.05),higher 72 h survival rate(P<0.05).② Mitochondrial preconditioning significantly enhanced PPP activation and NADPH-mediated antioxidative capacity,Mito-PC+H2O2 vs PC+H2O2 showed improved cell viability(P<0.05),Mito-PC vs PC showed increased G6PD activity(P<0.05),decreased NADP+/NADPH ratio(P<0.05).Conclusion Mitochondrial preconditioning potentiates pericyte-mediated protection against sepsis-induced pulmonary vascular leakage through enhanced pentose phosphate pathway activity.Mitochondrial preconditioning potentiates pericyte-mediated protection against sepsis-induced pulmonary vascular leakage through enhanced pentose phosphate pathway activity.

Cysteine protease inhibitor SN(Cystatin SN , CST1), a member of the type 2 cystatins superfamily, regulates tumor biological activities by modulating cysteine protease activity. CST1 is abnormally expressed in digestive system neoplasms, such as esophageal cancer, gastric cancer, hepatocellular carcinoma, colorectal cancer, and pancreatic cancer. CST1 influences tumor cell proliferation, migration, and epithelial-mesenchymal transition (EMT) through signaling pathways including Wnt, STAT3, and PI3K-AKT. Its expression levels significantly correlated with tumor stage, metastasis, and patient prognosis, suggesting its potiential as a novel biomarker for early diagnosis, therapeutic evaluation, and prognosis in digestive system neoplasms. This article systematically reviews the molecular characteristics of CST1, its mechanisms of action in digestive system neoplasms, clinical significance, and explores its potential as a therapeutic target.