Objective To explore the transcriptional regulatory effect of p53 on tissue inhibitor of metalloproteinases 2(TIMP2)and its role in the biological functions of colorectal cancer cells. Methods Differentially expressed genes were screened using transcriptome data of p53-deficient HCT116 cells.Two colorectal cancer cell lines,HCT116 and HCT8,were selected,and the transcriptional regulatory effect of p53 on TIMP2 was measured by qRT-PCR and Western blotting under p53 knockdown and activation conditions.The direct transcriptional regulation of TIMP2 by p53 was verified via combining the JASPAR database and dual-luciferase reporter assay.The cell scratch and Transwell assays were used to detect the effects of p53 overexpression and TIMP2 depletion on tumor cell migration and invasion.The TCGA database was used to analyze TIMP2 expression and survival in cancer and adjacent normal tissues in colorectal cancer(TCGA-COAD). Results RNA-seq analysis showed TIMP2 was among the significantly differentially expressed genes.In HCT116 and HCT8 cells,TIMP2 mRNA and protein levels were positively correlated with p53.p53 could directly activate TIMP2 transcription,thereby suppressing tumor malignant phenotypes.The TCGA database showed low TIMP2 expression in COAD tumors,which was associated with poor prognosis in colorectal cancer patients. Conclusion TIMP2 is lowly expressed in colorectal cancer cells,and p53 partially inhibits tumor cell metastasis by transcriptionally regulating TIMP2,indicating that TIMP2 is expected to become a potential target for the future treatment of colorectal cancer.

Objective To investigate the protective effect of the G protein-coupled estrogen receptor(GPER)against endotoxin-induced hepatocyte injury and its underlying molecular mechanism,and to evaluate its potential as a sex-specific therapeutic strategy. Methods An AML-12 mouse hepatocyte model induced by lipopolysaccharide(LPS)was used to simulate the early pathological processes of septic liver injury.The cells were divided into four groups:blank control,LPS,LPS+G1(a GPER agonist),and LPS+G15(a GPER antagonist).Techniques including flow cytometry,Western blot,RT-qPCR,ELISA,and transmission electron microscopy were employed to assess apoptosis rate,GPER expression,mtROS,MDA,NLRP3 inflammasome activation,IL-1β levels,ATP/AMP ratio,ΔΨm,and ultrastructural changes. Results Compared with the LPS group,G1 treatment significantly reduced the apoptosis rate,suppressed mtROS and MDA production,downregulated the NLRP3/Caspase-1/IL-1β signaling pathway,increased ATP level,decreased the AMP/ATP ratio,and ameliorated mitochondrial membrane potential and ultrastructure.In contrast,G15 exacerbated these injuries.Correlation analysis showed that GPER expression was negatively correlated with the apoptosis rate(R²=0.8970),while mtROS levels were positively correlated with both apoptosis rate and IL-1β content. Conclusion GPER activation alleviates septic liver injury by inhibiting mtROS production,blocking NLRP3 inflammasome activation and subsequent inflammatory responses,and improving mitochondrial energy metabolism and structural integrity.This mechanism provides a novel target and theoretical basis for sex-specific treatment strategies in clinical practice.

Objective To investigate the expression of agouti signaling protein(ASIP)in the placenta of pregnant women with different glucose tolerance,as well as its effect,under high-glucose conditions,on trophoblast cell proliferation,invasion,and tube formation. Methods Placental tissues were collected from pregnant women with gestational diabetes mellitus(GDM,n=20)and without GDM(non-GDM,n=20).ASIP expression and localization were detected by immunohistochemistry and immunofluorescence.The human trophoblast cell line HTR-8/SVneo was cultured under high-glucose conditions and treated with recombinant ASIP or the peroxisome proliferator-activated receptor γ(PPARγ)antagonist GW9662.Cell proliferation,invasion,and tube formation were assessed using MTT,Transwell,and Matrigel assays,respectively.Western blotting assay and RT-qPCR were performed to analyze protein and mRNA expression. Results Placental weight was significantly higher in the GDM group than in the non-GDM group(570 g vs 490 g,P=0.019).ASIP mRNA and protein levels were significantly upregulated in GDM placental villous trophoblasts,and immunohistochemistry and immunofluorescence further confirmed significantly increased ASIP protein expression in the placental villous trophoblasts.Under high-glucose conditions,the expression levels of ASIP mRNA and protein in HTR-8/SVneo cells were significantly increased.Subsequently,recombinant ASIP(50-200 ng/mL)promoted cell proliferation and induced the phosphorylation of PPARγ,signal transducer and activator of transcription 1(STAT1),and STAT3 in a dose-dependent manner.Furthermore,treatment of HTR-8/SVneo cells with ASIP(200 ng/mL)for 24 h significantly enhanced trophoblast proliferation,invasion,and tube formation.The promoting effects of ASIP were partially reversed by co-treatment with the PPARγ antagonist GW9662(20 μmol/L). Conclusion ASIP expression is elevated in trophoblast cells under both GDM and high-glucose conditions.ASIP promotes excessive proliferation,invasion,and tube formation of trophoblast cells via a PPARγ-dependent mechanism under high-glucose conditions,thereby contributing to the placental remodeling of GDM.

Objective To investigate the effect of platelet activation on the apoptosis of endothelial cells. Methods Platelets were prepared from venous blood,obtained from healthy subjects.Resting platelet suspension,activating platelet suspension,and endothelial cells were cultured in vitro to establish the co-culture model of platelets and endothelial cells.The aggregation,adhesion and release process of platelets after activation and the apoptosis process of endothelial cells were observed by live-cell imaging technique.The endothelial cell survival activity and mitochondrial membrane potential were then detected by kits. Results Activated platelets exhibited significant aggregation,adhesion,and release responses.Compared to resting platelets,activated platelets aggregated,migrated toward endothelial cells,and adhered to them.Live-cell imaging revealed that activated platelets induced nuclear pyknosis,condensation,marginalization,reduced nuclear volume,fragmentation,and the formation of apoptotic bodies in endothelial cells.Compared to the resting platelet group,the activated platelet group showed reduced endothelial cell viability and mitochondrial membrane potential. Conclusion Platelet activation induces apoptotic injury in endothelial cells.

Objective To investigate the multi-target mechanism of quercetin,the main active component of Rosa chinensis(R.chinensis),against Aspergillus fumigatus(A.fumigatus) from the host-pathogen interaction perspective. Methods Firstly,the active components of R.chinensis and host targets related to A.fumigatus infection were screened using TCMSP,GeneCards,and OMIM databases.Virulence and drug resistance-related targets of A.fumigatus were obtained from NCBI and UniProt databases.Cross-species homology mapping was performed using the KEGG Orthology system,and a Host-Pathogen Pathway Interaction Network(HPPIN)was constructed using Cytoscape 3.10.3.Core targets were identified through topological analysis(degree centrality and betweenness centrality).Secondly,molecular docking of quercetin with the core targets was conducted using AutoDock Vina 1.5.7,with a binding energy threshold of ≤ -5.0 kcal/mol.The optimal complex was selected for a 100 ns molecular dynamics simulation using GROMACS 2020.6(AMBER99SB force field)to analyze binding stability via root-mean-square deviation(RMSD),root-mean-square fluctuation(RMSF),and hydrogen bond numbers.Finally,following the CLSI M38-A3 protocol,the minimum inhibitory concentration(MIC)of quercetin against the standard A.fumigatus strain Af293 was determined using the broth microdilution method.Phenotypic rescue experiments using a mixture of N-acetylcysteine and purine were performed to validate the predicted interference with oxidative stress and purine metabolism pathways,and hyphal morphological changes were observed under an inverted microscope. Results The HPPIN identified 12 key targets.Quercetin exhibited binding energies of-7.6 kcal/mol with KRas and-7.8 kcal/mol with SAICAR synthetase,forming stable complexes(RMSD<0.2 nm).The MIC of quercetin against A.fumigatus was 256 μg/mL,resulting in complete inhibition of hyphal growth.This inhibitory effect was reversed by N-acetylcysteine,confirming the role of oxidative stress.Concurrently,combination with high-concentration purine led to complete germination failure,indicating disruption of purine metabolism. Conclusion Quercetin synergistically inhibits A.fumigatus through dual mechanisms of “starvation” and “intoxication.”

Objective To identify key molecular biomarkers of acute coronary syndrome(ACS)through transcriptome sequencing and construction of mRNA-lncRNA co-expression networks. Methods An ACS mouse model was established,and the modeling outcomes and cardiac pathological changes were comprehensively evaluated using physiological and pathological assays.RNA sequencing(RNA-seq)was performed to obtain gene expression profiles across different samples.Bioinformatics analysis was then applied to explore gene expression changes and functional signaling pathways associated with ACS. Results After ACS modeling,experimental results such as HE staining,TTC staining,and Doppler ultrasound all indicated that ACS led to histopathological changes and dysfunction in mouse cardiac tissue.RNA-seq results revealed 2 557 DEGs that were co-upregulated in both ACS-M and ACS-S,and 1 930 DEGs that were co-downregulated,including mRNAs(DEmRNAs)and lncRNAs(DElncRNAs).Further GO functional enrichment analysis showed that these DElncRNAs regulated the differential expression of target genes related to mitochondrial function,fatty acid metabolism,immune/inflammatory response,cell adhesion,apoptosis,fibrosis,and other functions.Additionally,six expression patterns closely associated with ACS were identified.Among them,lncRNAs Dnm3os and Gm13054 were persistently highly expressed in ACS and their high expression characteristics were validated by RT-qPCR.Their downstream targets were closely related to mitochondrial function and tissue fibrosis.Gm13054 also exhibited potential regulatory functions for Nppa expression. Conclusion This study identified a large number of DEmRNAs and DElncRNAs through RNA-seq,which have potential functions tightly associated with ACS.The construction of a co-expression network between mRNAs and lncRNAs provides potential therapeutic targets and a foundational basis for further clinical research on the diagnosis and treatment of ACS.

Objective To investigate the predictive value of serum chemokine(C-C motif)ligand 5(CCL5)and chemokine(C-C motif)ligand 13(CCL13)for early renal injury in children with IgA vasculitis(IgAV). Methods A total of 267 children with IgAV treated at the 940th Hospital of the Joint Logistics Support Force of the Chinese People’s Liberation Army from January 2023 to March 2025 were enrolled.According to the presence or absence of renal injury,they were divided into an IgA vasculitis with nephritis(IgAVN)group(n=94)and an IgAV-without-nephritis group(n=173).Clinical data were collected.Serum CCL5 and CCL13 levels were measured by enzyme-linked immunosorbent assay.Spearman correlation was used to evaluate the relationship between CCL5 and CCL13 in IgAVN patients.Differences in CCL5 and CCL13 among IgAVN clinical subtypes were compared.Multivariate logistic regression was performed to identify independent risk factors for early renal injury in children with IgAV,and a nomogram was constructed.ROC curves,calibration curves,and decision-curve analysis were used to assess the model’s predictive performance.ROC curve analysis was also used to evaluate the diagnostic value of serum CCL5 and CCL13 for early renal injury. Results The IgAVN group showed significantly older age and higher neutrophil-to-lymphocyte ratio(NLR)than the IgAV group(both P<0.05).Serum CCL5 and CCL13 levels were also markedly elevated in the IgAVN group(both P<0.05).Spearman analysis revealed a significant positive correlation between serum CCL5 and CCL13 in IgAVN patients(r=0.339,P<0.001).CCL5 and CCL13 levels differed among IgAVN clinical subtypes and increased with disease severity(P<0.05).Multivariate logistic regression indicated that increased age,elevated NLR,and higher serum CCL5 and CCL13 levels were independent risk factors for early renal injury in children with IgAV.The nomogram based on these factors demonstrated good predictive performance and clinical utility.ROC curve analysis showed that serum CCL5 and CCL13 were effective biomarkers for diagnosing early renal injury in children with IgAV. Conclusion Elevated serum CCL5 and CCL13 levels are closely associated with early renal injury in pediatric IgAV patients.Combined detection of these markers holds significant value for assessing the occurrence of early renal injury.

Objective To explore the efficacy and mechanisms of the receptor for advanced glycation end products inhibitor TTP488 in reducing retinal inflammation. Methods Thirty male C57BL/6J mice were randomly divided into 3 groups(n=10 each):control group,type I diabetes mellitus(T1DM) model group,and T1DM+TTP488 group.A T1DM mice model induced by streptozotocin(STZ)was established.Immunofluorescent staining targeting microglial cell markers(Iba1)was used to determine the activation degree of Iba1-positive cells in the retinal tissues of mice;and ELISA was used to measure the levels of inflammatory factors TNF-α,IL-1β and IL-6 in them.mRPE cells was divided into the following 5 groups for the further in vitro cell experiments:control group,LPS group,LPS+TTP488 group,LPS+shRNA-P65 group,LPS+shRNA-NT group.Lipopolysaccharide(LPS)was used to establish the primary mouse retinal pigment epithelial cells inflammatory model.Adenovirus vector was used to mediate the knockdown of P65.The expression level of VEGF-D mRNA in cells was determined by RT-qPCR.The expression levels of phosphorylated NF-κB P65(p-P65)/P65 and VEGF-D in the retinal tissues of mice as well as in in vitro cells were determined by Western blotting. Results Compared with those in the T1DM model group,the number of Iba1 positive cell branches and the number of Iba1 positive cell branch connection points(per field)in the T1DM+TTP488 group were decreased(P<0.05).The levels of TNF-α,IL-1β,and IL-6 were decreased(P<0.05).The relative expression levels of p-P65/P65 and VEGF-D were decreased(P<0.05).Compared with those in the LPS group,the relative expression level of VEGF-D mRNA in the LPS+TTP488 group and the LPS+shRNA-P65 group was decreased(P<0.05).The relative expression levels of p-P65 and VEGF-D were down-regulated(P<0.05). Conclusion TTP488 reduced the expression of VEGF-D by inhibiting the activation of NF-κB,thereby alleviating retinal inflammation and tissue structural abnormalities in the diabetic retinopathic mice model.

Objective To investigate the effect of 1β-hydroxyalantolactone(1β-HA)on hepatic injury in rats with nonalcoholic steatohepatitis(NASH)through the AMPK/SREBP-1c signaling pathway. Methods A rat model of NASH was established by feeding with high-fat diet.The rats were administered 1β-HA at doses of 12.5,25.0,and 50.0 mg/kg by oral gavage for 4 weeks.Serum levels of HDL,TG,ALT,and AST were measured.Hepatic histopathology was assessed.The protein expression levels of α-SMA,MMP-1,TIMP-1,AMPK,and SREBP-1c were detected.The levels of IL-6,TNF-α,and IL-1β,as well as SOD activity and MDA concentration,were evaluated. Results Compared with the model group,the 1β-HA treatment groups showed significantly increased HDL levels and decreased TG,AST,and ALT levels(P<0.05);hepatic steatosis,inflammatory infiltration,and fibrosis were alleviated;the expression levels of α-SMA,TIMP-1,and SREBP-1c were down-regulated,while those of MMP-1 and AMPK were up-regulated(P<0.05);the levels of IL-6,TNF-α,and IL-1β were reduced;SOD activity was elevated,and MDA concentration was decreased(P<0.05). Conclusion 1β-HA can ameliorate hepatic injury in NASH by activating AMPK and inhibiting the expression of SREBP-1c.

Silent information regulator 1(SIRT1),a core member of the Sirtuin family,is an NAD⁺-dependent class Ⅲ histone deacetylase that plays a crucial role in the epigenetic regulatory network.By mediating the deacetylation of a variety of histone and non-histone substrates,SIRT1 broadly regulates key physiological processes such as lipid metabolism,oxidative stress,inflammatory response,and apoptosis.Current studies indicate that dysregulation or functional impairment of SIRT1 is closely associated with the occurrence and progression of liver diseases.This article summarizes the specific mechanisms of SIRT1 in alcohol-associated liver disease,metabolic dysfunction-associated steatotic liver disease,viral hepatitis,liver fibrosis,and hepatocellular carcinoma.Additionally,the potential applications of SIRT1-targeted interventions in the treatment of chronic liver diseases are briefly discussed,with the aim of providing deeper insights into its unique regulatory mechanisms and offering a theoretical basis for developing more precise therapeutic strategies.

Obesity is a prominent and highly detrimental public health crisis worldwide.Its essence lies in a chronic imbalance between energy intake and expenditure,directly involving complex networks of central appetite regulation,adipose tissue metabolism,and systemic inflammation.Autophagy is a highly conserved and well-defined intracellular degradation pathway that clears damaged organelles,protein aggregates,and lipid droplets,thereby intrinsically participating in energy recycling and metabolic regulation.Specifically,in adipose tissue,autophagy promotes adipogenesis and lipid storage in white adipose tissue,participates in mitochondrial clearance and the whitening process in brown/beige adipose tissue to modulate thermogenesis,and attenuates pro-inflammatory responses in adipose tissue macrophages by reducing mitochondrial reactive oxygen species and inhibiting NLRP3 inflammasome activation,thereby regulating tissue inflammation.More importantly,autophagy in hypothalamic POMC and AgRP neurons directly regulates neuropeptide processing and secretion,thus serving as a critical molecular switch for central control of appetite and energy expenditure.Obesity-related autophagy genes play clear and essential roles in adipogenesis,thermogenic regulation,inflammatory responses,and neuronal function;their dysregulation inevitably leads to lipid accumulation,insulin resistance,and chronic inflammation,forming a central-peripheral,mutually reinforcing network of metabolic dysregulation.Consequently,nutritional interventions,pharmacological activation,and miRNA-mediated precision interventions based on autophagic regulatory mechanisms all show great promise for ameliorating obesity and related metabolic disorders.Therefore,systematically and rigorously elucidating the role of autophagy in adipose tissue,the central nervous system,and systemic metabolic regulation will help clarify the molecular mechanisms underlying obesity and,more importantly,facilitate the design of effective tissue-specific intervention strategies.

Tumor-associated macrophages(TAMs)constitute a critical component of the tumor immune microenvironment and are closely linked to the initiation,progression,and metastasis of tumors.Influenced by the tumor microenvironment,the functional plasticity of TAMs determines their diverse roles in tumor immunity.This review summarizes macrophage iron metabolism and its role in tumor immunity,providing insights into the prospects and specific regulatory mechanisms of macrophage-targeted therapy.

Integrins are a class of heterodimeric transmembrane receptors that play a pivotal role in mediating tumor growth,invasion,and drug resistance by interacting with the tumor microenvironment and regulating signaling pathways such as Wnt/β-catenin,FAK,and MAPK.Numerous studies have demonstrated that the expression levels of certain integrins in head and neck squamous cell carcinoma(HNSCC)are closely associated with malignant progression and prognosis.This article reviews the roles of key integrins in the malignant progression and drug resistance of HNSCC,as well as their multidimensional communication between tumor cells,immune cells,and stromal cells within the tumor microenvironment.

Autophagy plays a dual regulatory role in the development of cervical cancer.Studies indicate a mutually inhibitory relationship between the Wnt/β-catenin signaling pathway and cellular autophagy:activated Wnt pathway suppresses autophagy by downregulating Beclin 1 and inhibiting GSK-3β,while autophagy can degrade Dvl protein to restrict excessive activation of the Wnt pathway.In cervical cells,this pathway can be aberrantly activated through various mechanisms:for example,the E6 protein upregulates the downstream target gene cyclin D1 and E7 protein to release the PP2A inhibition;the non-coding RNA circRNF121 reactivates Wnt signaling;and the non-coding RNA NEAT1 increases the nuclear β-catenin accumulation.These mechanisms subsequently modulate autophagy in cervical cells and promote tumor progression.Targeting key components of this pathway may offer new strategies for cervical cancer treatment.Future exploration of the bidirectional regulatory mechanisms of the Wnt pathway on autophagy will advance the development of precision therapy.

Autologous hematopoietic stem cell transplantation(ASCT)is the standard treatment for multiple myeloma,a malignant hematologic disorder,yet some patients exhibit poor prognosis.Double ASCT achieves deeper remission through two transplants within a short period.Studies indicate that compared to single ASCT,double ASCT offers certain advantages in prolonging progression-free survival and overall survival,particularly in high-risk patients such as those with del(17p)or IGH rearrangements.

Aging is a complex biological process marked by the progressive decline of physiological functions over time,accompanied by lifespan-wide,multilevel,and dynamically evolving changes in cellular and molecular networks.Lipids,as essential molecules for cellular membrane architecture,energy storage,and signal transduction,play critical roles in maintaining cell function and homeostasis.Dysregulation of lipid metabolism may serve as an important driving force in aging and a wide range of human diseases.In recent years,advances in lipidomics technologies have enabled systematic characterization of dynamic lipidome alterations during aging in multiple model organisms as well as in humans.These studies have gradually revealed both conserved age-associated lipidomic patterns and tissue-specific remodeling features.Here,we briefly review recent lipidomics findings from mouse and human aging studies,highlight major advances in the field,and discuss current challenges and future perspectives.

Adipose tissue serves as a critical energy storage depot and endocrine organ,and its aging profoundly impacts systemic metabolic homeostasis and multi-organ functions.This review systematically outlines the core features of adipose tissue aging,including macroscopic redistribution,extracellular matrix fibrosis,cellular dysfunction(encompassing adipocytes,progenitor cells,immune cells,and senescent cells),and endocrine dysregulation.Aging leads to ectopic lipid deposition in white adipose tissue,diminished thermogenic capacity of brown adipose tissue,decreased adiponectin levels,and increased secretion of pro-inflammatory factors,collectively driving chronic low-grade inflammation and insulin resistance.These alterations further exacerbate the development of age-related diseases such as cardiovascular disorders,metabolic dysfunction-associated steatotic liver disease,and tumors.Current intervention strategies targeting adipose tissue aging primarily include caloric restriction,metformin,and PPARγ agonists,yet their clinical application faces limitations.Future research should focus on elucidating the spatiotemporal mechanisms of adipose aging and developing more targeted therapeutic approaches.

Objective To explore the application effect of the “Digital Intelligence+Group Learning” model in molecular biology teaching,in order to address the challenges of traditional teaching in personalized support and the cultivation of high-order abilities. Methods A total of 750 five-year undergraduate students were selected and divided into an experimental group(adopting Digital Intelligence+Group Learning)and a control group(adopting traditional lecture-based teaching).A mixed research method was used for evaluation. Results The experimental group performed significantly better than the control group in formative assessment(92.6±6.2 vs 85.4±8.7)and summative assessment(85.5±8.2 vs 80.3±9.1)(P<0.01),and also demonstrated better performance in knowledge integration,case analysis,and learning interest. Conclusion This model may effectively compensate for the deficiencies of traditional teaching to a certain extent,enhance students’ comprehensive abilities,and provide practical references for medical education reform.

Objective To comb and show the current situation,development trend and theme evolution process of artificial intelligence(AI)in medical education by knowledge map construction,to provide reference for the research on the direction of AI applied to medical education. Methods We searched and read 524 core documents of Web of Science from 2010 to 2024,and applied VOSviewer software,Citespace software and R language biblimetrix package respectively to analyse the evolution process of high-influence authors and research teams of AI in the field of medical education,and the current focus content and research content.evolutionary process. Results The AI-driven development of medical education has shown a marked upward trend since 2018;the field has established several stable core research teams,with strong internal collaboration within each team,though cooperation among large teams remains relatively loose;the Mayo Clinic is currently the research institution with the highest global publication output in this field,and collaboration is particularly close among institutions with high publication volumes;China currently ranks second in the world in terms of publication output on related topics;Furthermore,results from keyword clustering and the analysis of research topic evolution indicate that,over the past two years,research hotspots in the application of artificial intelligence to medical education have primarily shifted toward large language models,machine learning,and virtual surgery. Conclusion The application of AI in medical education is undergoing a transformation from auxiliary tools to intelligent empowerment systems,holding promise for advancing medical education toward greater intelligence,precision,and personalization.