ObjectiveThis study aimed to investigate the anti-Mycoplasma pneumoniae (MP) activity of luteolin and elucidate its underlying mechanisms. MethodsLuteolin was identified as the primary active compound from the polyphenol extract ofF. diotrys using network pharmacology. Its efficacy was evaluated against two MP strains: the standard strain M129 and the multidrug-resistant strain M19. A modified culture medium with visual characteristics was employed to determine the minimum inhibitory concentration (MIC) of luteolin. The expression of key proteins involved in MP growth and pathogenicity was assessed by qRT-PCR following luteolin treatment. Additionally, the viability of A549 cells infected with MP was compared between luteolin-treated and untreated groups. In vivo anti-MP activity was evaluated using a mouse model, and the expression of inflammatory cytokines in lung tissues was analyzed. ResultsLuteolin effectively inhibited both MP strains, with MIC₉₀ values of 100 mg/L for M19 and M129. Treatment with luteolin significantly downregulated the expression of adhesion proteins P1 and P30 in both strains. However, the expression of P65, HMW3, TrmB, and CARDS TX was reduced only in the M19 strain following luteolin intervention. Luteolin also enhanced the growth and viability of A549 cells infected with MP. In the mouse model, luteolin treatment resulted in steady weight gain and was well tolerated. The bacteriostatic rate of luteolin in lung tissues was 50.7%, significantly higher than the 25.2% observed in the roxithromycin group. Furthermore, luteolin reduced the expression of inflammatory factors, including IL-6, TNF-α, and HMGB1, in MP-infected mice. ConclusionLuteolin effectively and safely inhibits the proliferation and pathogenicity of MP, particularly the drug-resistant M19 strain, by downregulating the expression of toxicity-associated proteins (P1, P30, P65, HMW3, TrmB, CARDS TX) and modulating host inflammatory responses. These findings suggest that luteolin may offer a novel therapeutic strategy for treating MP infections, especially those caused by drug-resistant strains.

ObjectiveThis study aimed to investigate the anti-Mycoplasma pneumoniae (MP) activity of luteolin and elucidate its underlying mechanisms. MethodsLuteolin was identified as the primary active compound from the polyphenol extract ofF. diotrys using network pharmacology. Its efficacy was evaluated against two MP strains: the standard strain M129 and the multidrug-resistant strain M19. A modified culture medium with visual characteristics was employed to determine the minimum inhibitory concentration (MIC) of luteolin. The expression of key proteins involved in MP growth and pathogenicity was assessed by qRT-PCR following luteolin treatment. Additionally, the viability of A549 cells infected with MP was compared between luteolin-treated and untreated groups. In vivo anti-MP activity was evaluated using a mouse model, and the expression of inflammatory cytokines in lung tissues was analyzed. ResultsLuteolin effectively inhibited both MP strains, with MIC₉₀ values of 100 mg/L for M19 and M129. Treatment with luteolin significantly downregulated the expression of adhesion proteins P1 and P30 in both strains. However, the expression of P65, HMW3, TrmB, and CARDS TX was reduced only in the M19 strain following luteolin intervention. Luteolin also enhanced the growth and viability of A549 cells infected with MP. In the mouse model, luteolin treatment resulted in steady weight gain and was well tolerated. The bacteriostatic rate of luteolin in lung tissues was 50.7%, significantly higher than the 25.2% observed in the roxithromycin group. Furthermore, luteolin reduced the expression of inflammatory factors, including IL-6, TNF-α, and HMGB1, in MP-infected mice. ConclusionLuteolin effectively and safely inhibits the proliferation and pathogenicity of MP, particularly the drug-resistant M19 strain, by downregulating the expression of toxicity-associated proteins (P1, P30, P65, HMW3, TrmB, CARDS TX) and modulating host inflammatory responses. These findings suggest that luteolin may offer a novel therapeutic strategy for treating MP infections, especially those caused by drug-resistant strains.

BACKGROUND: Chronic kidney disease (CKD) is a progressive disorder that leads to significant structural and functional changes in the kidneys, posing a major global health concern and contributing to high mortality rates. METHODS: The urgent need for innovative treatments is evident. Mesenchymal stem cells (MSCs) are well-regarded in regenerative medicine for their ability to repair tissue and modulate immune responses. Emerging research indicates that the therapeutic benefits of MSCs are largely mediated by the secretion of extracellular vesicles (EVs), particularly exosomes (MSC-Exos), which replicate the effects of MSCs by delivering genetic materials and proteins to target cells. RESULTS: MSC-Exos are novel natural carriers for targeted gene or drug delivery, offering biocompatibility, intrinsic targeting capabilities, and bioactive cargo to modulate recipient cells. They represent a groundbreaking platform for precision medicine, enhancing therapeutic efficacy with minimal immunogenicity and off-target effects. Moreover, embedding exosomes within hydrogels has emerged as a promising strategy to maintain their biological activity and enable a controlled release. CONCLUSION This review explores the roles of MSC-Exos in CKD pathophysiology, highlights the renoprotective effects of MSC-Exos for various sources, and provides a comprehensive overview of how hydrogel biomaterials present a promising approach for integrating exosomes to enhance therapeutic outcomes. The use of hydrogels to encapsulate exosomes improves their sustained release and stability in diseased kidney tissues, providing an innovative strategy to enhance precision therapies.

Purpose: Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles. Materials and Methods: Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion. Results: The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88–0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column. Conclusions Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.

Knee osteoarthritis(OA)is a primary cause of joint dysfunction.Knee osteotomy has garnered significant attention due to its potential to delay the progression of knee OA and enhance joint function.As a pivotal biomechanical factor in the onset and progression of OA,the accurate correction of abnormal knee alignment is the central objective of knee osteotomy.This article systematically reviews the biomechanical research progress related to knee osteotomy,with a focus on the precision and personalized correction of force line.The development of new classification system and measurement technology of force line is summarized,the biomechanical mechanism of knee OA induced by abnormal mechanical load is analyzed,and the goal of force line and clinical application progress of knee osteotomy is discusses,so as to provide a new perspective and idea for the clinical treatment of knee OA with knee osteotomy.

Knee osteoarthritis(OA)is a primary cause of joint dysfunction.Knee osteotomy has garnered significant attention due to its potential to delay the progression of knee OA and enhance joint function.As a pivotal biomechanical factor in the onset and progression of OA,the accurate correction of abnormal knee alignment is the central objective of knee osteotomy.This article systematically reviews the biomechanical research progress related to knee osteotomy,with a focus on the precision and personalized correction of force line.The development of new classification system and measurement technology of force line is summarized,the biomechanical mechanism of knee OA induced by abnormal mechanical load is analyzed,and the goal of force line and clinical application progress of knee osteotomy is discusses,so as to provide a new perspective and idea for the clinical treatment of knee OA with knee osteotomy.

Brain age prediction is of great significance to the in-depth understanding of individual neurodevelopment,early diagnosis of neuropsychiatric disorders,and formulation of personalized treatment plans. With the continuous advancement of deep learning,more and more researches focus on using such algorithms to predict brain age. Compared with traditional regression algorithms,deep learning which has the advantages of complex pattern learning,end-to-end learning and high adaptability can more accurately reveal the neuropathological mechanisms of neuropsychiatric disorders,and provide more precise tools for clinical assessment,assisted diagnosis and prognosis prediction. Herein the study reviews the recent advances in the application of deep learning algorithms in brain age prediction,introduces the achievements in deep learning model optimization,multimodal data inputs and interpretability studies for brain age prediction,discusses the methods for the establishment of integrated deep learning architectures and the future challenges of developing unified benchmarking,and provides an outlook on the application of deep learning in brain age prediction.

Objective:To investigate the mechanism of Circ_0085315 on Treg mediated immune escape of colon cancer(CC)through miR-149-5p/immunity-related GTPase Q(IRGQ)pathway.Methods:Cancer and normal tissues of 50 CC patients were col-lected,CC cell lines(SW480,HCT116,HT29,SW620,Lovo)and human normal colon epithelial cells HCoEpiC were cultured in vitro,and the expression level of Circ_0085315 in tissues and cells was detected by qRT-PCR.CC cell line SW480 was used as the re-search object,bioinformatics analysis,double luciferase reporter gene experiment and RNA binding protein immunoprecipitation(RIP)experiment were applied to confirm the relationship between Circ_0085315,miR-149-5p and IRGQ,qRT-PCR was used to de-tect the expression levels of Circ_0085315,miR-149-5p and IRGQ mRNA in cells,CCK-8 was used to detect cell proliferation activity,flow cytometry was used to detect the apoptosis rate,Western blot was used to detect the expression of IRGQ,Ki-67,PCNA,Bcl-2,Bax,and Cleared caspase-3 proteins in cells,ELISA was used to detect the level of immune related cytokines in the co-culture system of CC cells and Treg,flow cytometry was used to detect the proportion of FOXP3+CD25+,FOXP3+CD4+,FOXP3+CD8+in the co cul-ture system of CC cells and Treg.The mouse tumorigenesis experiment was used to verify the influences of Circ_0085315 on CC tumor growth,miR-149-5p/IRGQ pathway and immune related cytokines.Results:Circ_0085315 was overexpressed in CC tissues and cell lines.According to bioinformatics analysis,double luciferase reporter gene experiment and RIP experiment,miR-149-5p might be the downstream target of Circ_0085315,and IRGQ might be a target gene of miR-149-5p.Silencing Circ_0085315 decreased the expres-sion levels of IRGQ mRNA and protein,and increased the expression level of miR-149-5p in CC cells(P<0.05);it decreased the survival rate of CC cells and increased the apoptosis rate,decreased the expression levels of Ki-67,PCNA,Bcl-2 proteins,while in-creased the expression levels of Bax and Cleaved caspase-3 proteins(P<0.05);it could also reduce the contents of IL-10 and TGF-β,and the proportions of FOXP3+CD25+and FOXP3+CD4+in the co-culture system of CC cells,and increase the contents of IL-2 and IFN-γ,and the proportion of FOXP3+CD8+(P<0.05).Further research results showed that inhibition of miR-149-5p expression could increase the expression level of IRGQ mRNA and weaken the influences of silencing Circ_0085315 on CC cell proliferation,apoptosis and immune escape.In vivo mouse tumorigenesis experiment showed that after silencing Circ_0085315,the expression level of IRGQ mRNA,tumor volume and weight were decreased,while the expression level of miR-149-5p was increased(P<0.05);in addition,the contents of IL-10 and TGF-β in peripheral blood serum were decreased,while the contents of IL-2 and IFN-γ were increased(P<0.05).Conclusion:Silence Circ_0085315 can not only inhibit CC cell proliferation and induce apoptosis,but also inhibit Treg mediated CC immune escape by regulating miR-149-5p/IRGQ pathway.

AIM:This study aims to investigate the changes in the lactylation levels of mitsugumin 53(MG53)protein during myocardial ischemia/reperfusion(I/R)and to further explore the potential molecular mechanisms by which MG53 lactylation impacts myocardial cell injury resulting from I/R.METHODS:A myocardial I/R model was established in mice through ligation of the left anterior descending coronary artery followed by reperfusion.Simultaneous-ly,a hypoxia/reoxygenation(H/R)model of rat myocardial H9C2 cells was created in vitro.In the mouse model,TTC and HE staining were employed to assess myocardial ischemia and injury.The levels of creatine kinase and cardiac troponin I were quantified using ELISA,while MG53 expression was evaluated through immunofluorescence.In the in vitro cell model,CCK-8 assay and flow cytometry were utilized to measure cell viability and apoptosis level,respectively.The levels of MG53 protein,its lactylation,and ferroptosis-related proteins in both mouse myocardial tissue and in vitro rat cardiomyo-cytes were analyzed using immunoprecipitation and Western blot.Additionally,the levels of reactive oxygen species,fer-rous ion,lactate dehydrogenase and malondialdehyde in tissues and cells were measured using appropriate assay kits.RE-SULTS:In the I/R group,mouse myocardial tissue exhibited significant injury following cardiac I/R.The expression of MG53 protein was reduced,while the lactylation level of MG53 protein and the ferroptosis of myocardial cells were in-creased.In the in vitro cardiomyocyte experiments,H/R exposure resulted in decreased cell viability,increased apoptosis and ferroptosis levels,reduced MG53 protein expression,and increased MG53 lactylation level.Treatment with 2-deoxy-D-glucose(2-DG)improved cardiomyocyte viability,decreased apoptosis and ferroptosis levels,increased MG53 expres-sion,and lowered MG53 lactylation level.Furthermore,the addition of exogenous lactate significantly countered the ef-fects of 2-DG on cell viability and MG53 expression,and increased the cell apoptosis,ferroptosis and MG53 lactylation levels.CONCLUSION:During myocardial I/R,there is a down-regulation of MG53 protein expression accompanied by an increase in the lactylation level of MG53 protein.The elevation of MG53 lactylation may exacerbate myocardial I/R inju-ry by facilitating the ferroptosis of cardiomyocytes.

This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.