Post-stroke cognitive impairment(PSCI)is a prevalent and debilitating complication of stroke that significantly hinders recovery and diminishes patients'quality of life.Repetitive transcranial magnetic stimulation(rTMS),a non-invasive neuromodulation technique,has garnered growing interest for its potential to enhance cognitive function in individuals with PSCI.Concurrently,resting-state functional magnetic resonance imaging(rs-fMRI),as a non-invasive neuroimaging technique,has emerged as a valuable tool for assessing spontaneous neural activity and functional connectivity in the brain.By offering in-sights into the neurobiological mechanisms underlying PSCI and the modulatory effects of rTMS,rs-fMRI provides a foundation for advancing precision-targeted interventions.This review aims to highlight recent progress in applying rs-fMRI to evaluate the efficacy and underlying mechanisms of rTMS in the treatment of PSCI.

Objective To investigate the protective effect and mechanism of paeoniflorigenone(PFG),a natural active com-ponent in Xiongshao Capsule,against oxidized low-density lipoprotein(ox-LDL)induced vascular endothelial cell injury.Methods Network pharmacology and molecular docking were employed to identify hub targets and key active components of Xiongshao Capsulefor treating atherosclerosis.Human umbilicalvein endothelial cells(HUVECs)were divided into control,ox-LDL(100 μg/mL),PFG low-dose(20 μmol/L),and PFG high-dose(80 μmol/L)groups.Thecytotoxicity of PFG(10-160 μmol/L)and ox-LDL(5-200 μg/mL)was evaluated using the cell counting kit-8(CCK-8)assay.The effects of PFG(10,20,40,80 μmol/L)on ox-LDL-induced HUVEC viability after 24 hours of intervention were detected.Apoptosis was measured by flow cytome-try.The release of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β)were quantified by enzyme-linked immunosorbent assay(ELISA).The mRNA expression levels of hub genes(EGFR,PIK3CA,SRC)were assessed by re-verse transcription quantitative PCR(qRT-PCR).Results Network pharmacology and molecular docking analysis demonstrated that PFG was a key active component of Xiongshao Capsule for treating atherosclerosis,stably binding to hub targets(EGFR,PIK3CA,and SRC)with binding affinities＜-7.0 kcal/mol.In vitro experiments revealed that compared to the control group,PFG-treated HUVECs showed no significant change in viability,while the ox-LDL group exhibited significantly reduced cell vi-ability,increased apoptosis levels,elevated concentrations of pro-inflammatory cytokines(TNF-α,IL-6,IL-1β),and upregulated mRNA expression of hub targets(EGFR,PIK3CA,SRC)(all P＜0.05).Compared to the ox-LDL group,PFG intervention sig-nificantly increased cell viability and decreased apoptosis levels,pro-inflammatory cytokine concentrations,and mRNA expres-sion of hub targets(all P＜0.05)in a dose-dependent manner.Conclusion This study demonstrates that PFG,the pivotal active ingredient of Xiongshao Capsule,may attenuate ox-LDL-induced vascular endothelial cell injury through the EGFR/PIK3CA/SRC regulatory axis.

Objective To verify the mechanism of bromodomain PHD finger transcription factor(BPTF)affecting develop-ment of glioma and ferroptosis by regulating the expression of solute carrier family 40 member 1(SLC40A1)in glioma cells by in v itro and invivo experiments.Methods U87MG cells were divided into sh-NC group,sh-BPTF group,sh-BPTF+ov-NC group and sh-BPTF+ov-SLC40A1 group.Cell lines were stably transfected by lentivirus,and the transfection efficiency was verified by qRT-PCR and Western blotting.Cell proliferation ability was detected by CCK-8 and plate clone formation test.Cell migra-tion and invasion ability were detected by Transwell.Cells were injected subcutaneously into nude mice to detect the tumor growth.To evaluate theferroptosis of cells,the reactive oxygen species(ROS)level,iron content,malondialdehyde(MDA)con-tent and reduced glutathione/oxidized glutathione(GSH/GSSG)ratio in cells were detected by corresponding kits.Co-immuno-precipitation(Co-IP)experiment was used to verify the interaction between BPTF and c-Myc protein.Chromatin immunoprecipi-tation(ChIP)experiment was used to verify that BPTF and c-Myc combined with SLC40A1 promoter.Double luciferase reporter gene experiment was used to verify theeffect of BPTF on SLC40A1 transcription.Results After BPTF knockdown,theexpres-sion of SLC40A1 in glioma cell was decreased,cell proliferation,migration,invasion in vitro,and tumor growth in vivo were in-hibited,iron content,ROS level and MDA content in cells were increased,and GSH/GSSG ratio in cell was de-creased.Overexpression of SLC40A1 reversed the inhibitory effect of BPTF on the proliferation,migration,invasion and tumor grow th in vivo,decreased the iron content,ROS level and MDA content in cells,and increased the GSH/GSSG ratio in cells.There was an interaction between BPTF and c-Myc proteins in gliomacells.A potential binding site of c-Mycin SLC40A1 promoter was verified,BPTF and c-Myc protein bound to SLC40A1 promoter.BPTF knockdown reduced the transcriptional ac-tivity of SLC40A1 promoter,and BPTF knockdown after binding site mutation did not affect the transcriptional activity of SLC40A1 promoter.Conclusion BPTF may upregulate the expression of its downstream target gene SLC40A1 by interacting with c-Myc,thereby inhibiting ferroptosis in glioma cells and promoting glioma progression.

Objective To optimized the ultrasonic-assisted extraction process of methyl geniposide from Mussaenda pu-bescens and investigated its antioxidant activity in vitro.Methods The yield of shanzhiside methyl ester from Mussaenda pu-bescens was used as an indicator.The optimal extraction process of shanzhiside methyl ester from Mussaenda pubescens w as ex-plored using single factor experiments and response surface methodology.The factors included methanol concentration,extrac-tion time,extraction temperature,and liquid-solid ratio.The in vitro antioxidant activity of Shanzhiside methyl ester from Mus-saenda pubescens was evaluated by the scavenging rate of DPPH free radical,hydroxyl radical,and superoxide anion free radi-cal.Results The optimal process for extracting glycosides from Mussaenda pubescens using ultrasound assisted method is meth-anol with a mass concentration of 55%,53℃extraction temperature,32∶1 liquid to material ratio,and extraction time of 98 mi-nutes.The yield of methyl ester of shanzhiside was(9.516±1.66)mL/g,and the yield of mountain hawthorn glycoside by re-gression model was 9.532 mg/g,with a relative error of less than 0.2%.After 5.5 hours of antioxidant testing reaction,4 μmol/L of geniposide methyl ester showed significant effects on DPPH·and the clearance rates of ABTS·were 95.18%and 98.75%,respectively,and the total antioxidant capacity of FRAP was 1.054 mmol/L Vc equivalent.Conclusion Response sur-face methodology can optimize the extraction process of shanzhiside methyl ester from Mussaenda pubescens,and the obtained Shanzhiside methyl ester exhibits excellent antioxidant activity in vitro.

The hypoxic microenvironment is one of the most distinctive features in solid tumors,shaping the microenviron-ment of cancer evolution and correlating with poor prognosis of patients.Transcriptional regulation mediated by hypoxia-induc-ible factors is an important modality in the mechanism of cellular sensing and adaptation to hypoxia.Recent studies have demon-strated that hypoxia plays a pivotal role in various biological processes,including tumor progression,autophagy,angiogenesis,the immune microenvironment,and metabolic reprogramming.This review comprehensively discusses the advances in under-standing hypoxia-driven biological processes within glioblastoma,laying a foundation for future targeted therapy aimed at tumor hypoxia.

Objective To investigate the function of Ring finger protein 13(RNF13)in cerebral ischemia reperfusion injury(CIRI),and its mechanism.Methods The mouse middle cerebral artery embolization and primary neuron oxygen-glucose depri-vation and reoxygenation were used as disease models.The CRISPR/Cas9 gene knockout technique,immunohistochemical stai-ning,immunofluorescence staining,Western blot and lipid peroxidation detection were used to evaluate the regulatory effect and molecular mechanism of RNF13 on ferroptosis in CIRI.Student's t test was used for the comparison of two samples,and one-way analysis of variance was used for the comparison of multiple samples.Results The expression levels of RNF13 protein in mice and primary neurons were upregulated during CIRI.After knockout of RNF13,ferritin heavy chain 1(Fth1)and ferritin light chain(Ftl)were downregulated,and the content of free ferrous ions and the accumulation of lipid peroxides in mice brain tissues were promoted,leading to ferroptosis aggravation and neurological impairments.Overexpression of RNF13 protected a-gainst ferroptosis by reducing the production of free ferrous and lipid peroxides in neurons.Conclusion RNF13 alleviates fer-roptosis in neurons after CIRI,and the effect is induced by Fth1.

Objective To investigate whether Porphyromonas gingivalis(Pg)in the oral cavity can influence the occurrence of perioperative neurocognitive disorder(PND)by modulating the TLR4/NF-κB signaling pathway.Methods In cell experi-ment,BV-2 cells in the logarithmic growth phase were randomly divided into two groups:the control group(Group C)and the LPS-Pg-treatedgroup(Group P).Western blot was used to detect the expression levels of signaling proteins(TLR4,NF-κB p65,NLRP3,TNF-α)in cellular proteins.Immunofluorescence assay was employed to observe thechanges in NF-κB p65 expres-sions inside and outside the nucleus.In animal experiments,C57BL/6 mice were randomly divided into six groups:the control group(Group C),the surgery group(Group S),the Pg infection group(Group P),the Pg infection+surgery group(Group PS),the TLR4inhibitor group(Group T),and the Pg infection+surgery+TLR4 inhibitor group(Group PST).After corresponding treatments,the Morris water maze(MWM)test was applied to observe theeffects of Pg infection on postoperativecognitive be-havior in mice.Immunohistochemical analysis was used to assess the impact of Pg infection on the activation of microglia in the hippocampal tissue of mice.Results In cell experiment,compared with Group C,expression levels of TLR4,NLRP3,and TNF-α increased significantly in Group P(all P＜0.05).The expression of NF-κB p65 in the nucleus increased(P＜0.05),while its expression outside the nucleus decreased(P＜0.05).Immunofluorescence results showed increased NF-κB expression and its translocation into the nucleus in Group P.As for animal experiment,no significant difference was observed in the preoperative training phase among the groups in Morris water maze experiment,with similar escape latencies and average swimming speeds(all P＞0.05).Therefore,therewas no notabledifferences in navigationand swimming abilities among thegroups before theex-periment.In the postoperative testing phase,compared with Group C,the target quadrant time and platform-crossing times were less in mice of Group S and Group PS(all P＜0.05).Compared with Group PS,the target quadrant time and platform-crossing times were elevated in mice of Group PST(both P＜0.05).Compared to Group C and Group PST,number of positive cells in hippocampal tissue was higher in Group PS.These positivecells exhibited enlarged somas,shortened processes,and an activated state of microglia.Conclusion Pg infection induces enhanced central nervous system inflammation during the perioperative peri-od in mice,leading to the occurrence of PND,possibly through the activation of the TLR4/NF-κB signaling pathway.

Tertiary lymphoid structure(TLS)is ectopic lymphoid-like organs induced under pathological conditions such as chronic inflammation and tumor microenvironment,which exhibits functional characteristics similar to secondary lymphoid or-gans and is commonly observed in various cancers.This review focuses on the biological characteristics of TLS in oral squamous cell carcinoma(OSCC),summarizing their components,formation mechanisms,and maturation stages within the tumor microen-vironment.It systematically analyzes the interrelationships between TLS features,including maturation levels,spatial distribu-tion,and cellular composition,and the progression and prognosis of OSCC.The review highlights the bidirectional interactions between TLS and microbial colonization in OSCC,as well as the impact of TLS on the efficacy of radiotherapy and chemotherapy and their potential predictive value for treatment responses.

Objective To examine the mechanism by which the HDAC3-Akt signaling pathway regulates the proliferation of aortic smooth muscle cells.Methods Rabbit vascular smooth muscle cells(rVSMCs)were subjected to various treatments,in-cluding DMSO(control),RGFP966(HDAC3 inhibitor),Flag(control for gene intervention),HDAC3 overexpression,and HDAC3 overexpression combined with Akt inhibitor MK2206.The5-Ethynyl-2'-deoxyuridine(EdU)assay and thecell counting assay were used to detect the proliferative capacity of cells in each group.The expression level of PCNA,p-H3,Akt and p-Akt in each group were examined by Western blotting.Results Compared with the control group(DMSO),the expression levels of p-Akt,PCNA,and p-H3 in the RGFP966 inhibitor group were significantly decreased(all P＜0.05).Concurrently,both the cell counting and EdU assays demonstrated a reduction in proliferation in the RGFP966-treated group compared to the DMSO group(both P＜0.05).In contrast,the HDAC3 overexpression group exhibited a significant increase in the expression levels of p-Akt,PCNA,and p-H3 compared to the Flag group(all P＜0.05).Cell counting assay and EdU assay showed that the prolifera-tion level in the HDAC3 overexpression group was elevated compared with the Flag group(both P＜0.05).Akt inhibitor MK2206 could reversed this effect induced by HDAC3 overexpression.Conclusion HDAC3 can effectively promote the prolif-eration of aortic smooth muscle cells,which might be mediated through Akt signaling pathway.

Objective To investigate shared mechanisms and therapeutic targets between heart failure(HF)and vascular de-mentia(VaD),and identify natural compounds for dual-organ protection.Methods Single-cell data(8 samples)from GEO were processed via Seurat for clustering.Through CellChat,inter-organ communication was constructed,and top 95%ligand-receptor pairs were analyzed by KEGG enrichment.Bulk RNA-seq(70 samples)underwent differential gene(limma)and immune infiltra-tion(CIBERSORT)analyses.31186 compounds from TCMbank werescreened by AutoDock Vina,followed by molecular dynam-ics validation.Results HF fibroblasts(43.75%,7 subclusters)and VaD oligodendrocytes(76.57%,6 subclusters)dominated re-spective tissues.Cross-disease integration revealed HF-driven fibrosis(COLLAGEN)and VaD-associated neuroinflammation(SPP1),converging on PI3K-Akt and ECM pathways.HF-specific markers(TNXB/THBS4/COL1 A2)and VaD signatures(SPP1/PDGFC/TGFA)were identified,with FOXC1 identified as a shared transcriptional regulator.B cell activation character-ized immune dysregulation.Among 8 FOXC1 inhibitors,Qingdainone showed optimal binding[affinity:-9.0 kcal/mol;RMSD:(0.2±0.06)nm].Conclusion This study uncovers fibrosis-neuroinflammation crosstalk in HF-VaD comorbidity and proposes Qingdainone as a FOXC1-targeting therapeutic candidate.