Abstract: Objective To investigate the role of caveolin-1 ( CAV1) in the progression of metabolicassociated fatty liver disease (MAFLD) and its potential mechanisms of action. Methods We identified differential CAV1 expressions in normal, obese, and non-alcoholic fatty liver disease individuals based on the human database GSE126848. A CAV1-knockout (KO) MAFLD mouse model was established by feeding with a high-fat diet for 16 weeks. CAV1 protein expression in the liver was determined by albumin and CAV1 co-localization, and CAV1 mRNA and protein levels were detected in primary hepatocytes. Lipid deposition and inflammation were assessed by hematoxylin-eosin, Oil Red O, and Nile Red staining. Mitochondrial damage was observed by transmission electron microscopy. Cellular senescence and iron metabolism changes were evaluated by immunohistochemistry for cyclindependent kinase inhibitor 1A (P21), dihydroethidium staining, and iron staining. We also constructed hepatocyte senescence models and divided them into blank control( Control), palmitic acid ( PA), palmitic acid with CAV1 silencing control group ( PA+Con-siRNA), palmitic acid with CAV1-small interfering RNA( PA+CAV1-siRNA),palmitic acid with CAV1 overexpression control group( PA+Con-GV107), palmitic acid with CAV1 overexpression groups( PA + CAV1-GV146), palmitic acid with CAV1 silencing and deferoxamine group ( PA + CAV1-siRNA +DFO). Lipid deposition, senescence, and Fe²⁺levels were analyzed, and the effects of CAV1 on hepatocyte senescence and mitochondrial function were validated by Western blot, quantitative reverse transcription-polymerase chain reaction, and mitochondrial membrane potential detection (JC-1) assays. Results In vivo experiments showed that the compared with WT+HFD group, KO+HFD exacerbated lipid deposition, inflammation, and liver senescence,as evidenced by enhanced lipid staining, increased levels of senescence markers, including histone H2A variant X phosphorylation, cyclin-dependent kinase inhibitor 2A ( P16), and P21 ( all P<0. 01), decreased levels of the oxidative stress markers glutathione(P<0. 05)and superoxide dismutase(P<0. 01), increased reactive oxygen species (ROS) and malondialdehyde ( P<0. 001), and mitochondrial shrinkage with increased mitochondrial membrane density. CAV1 KO also decreased Fe³⁺(P<0. 01) and increased Fe²⁺ accumulation(P<0. 001), associated with the nuclear receptor coactivator 4-ferritin heavy chain 1 (NCOA4-FTH1) pathway. Compared with KO+HFD+CSD-CON group, supplementation with the CAV1 scaffolding domain significantly improved the reduction of Fe³⁺and the accumulation of Fe²⁺ (both P<0. 01). Compared with the PA+Con-siRNA group, the PA+CAV1-siRNA group showed accelerated lipid accumulation, mitochondrial damage, and cellular senescence, accompanied by elevated mitochondrial reactive oxygen species(mtROS)levels, Fe²⁺ accumulation, increased NCOA4 expression(P<0. 001),and decreased FTH1 expression(P<0. 05), while CAV1 overexpression attenuated these effects(P<0. 05,P<0. 01).Immunofluorescence revealed that CAV1 silencing enhanced NCOA4 and FTH1 co-localization, and this effect was reversed by CAV1 overexpression. Notably, Compared with the PA+CAV1-siRNA group, treatment with deferoxamine (DFO) reduced mtROS levels and ameliorated the senescence induced by CAV1 silencing ( all P<0. 001 ).Collectively, these result indicate that CAV1 modulates liver senescence, potentially via the NCOA4-FTH1 pathway. Conclusions CAV1 can inhibit MAFLD hepatocyte senescence, possibly by regulating iron homeostasis via the NCOA4-FTH1 pathway.

Abstract: Objective To study the effect of Xiongmatang active ingredients on intestinal microbes in a rat migraine model. Methods One hundred and twenty rats underwent dural cannulation surgery, and general physical signs were observed. Ninety healthy rats were selected and injected with inflammation soup six times within 12 days to stimulate the dura mater to create a migraine model. These rats were randomly divided into nine groups of 10 rats:model, calcitonin gene-related peptide ( CGRP ) inhibitor, flunarizine-positive ( Flunarizine), and Xiongmatang active ingredients (low- and high-dose groups for n-butanol, ethyl acetate, and n-butanol + ethyl acetate extracts).An additional control group of 10 rats was established, injected with 0. 9% sodium chloride solution using the same modeling procedure. After successful modeling, the control and model groups were given pure water by gavage, and the CGRP inhibitor group were given the drug by tail vein five times, once a week; the other groups were given corresponding doses, once a day, for a total of 4 weeks (28 d). Behavioral assessments were then conducted using sucrose preference, tail suspension, novel object recognition, and Morris water-maze tests. Abdominal aortic blood was collected for enzyme-linked immunosorbent assay quantification of circulating CGRP and NO levels. Intestinal contents were taken, and the changes in the gut microbiota were analyzed by 16S rDNA high-throughput sequencing. Results Compared with the control group, model group rats exhibited significant depressive-like behavioral changes and cognitive impairments, meanwhile, the contents of CGRP and NO in serum were significantly increased ( P<0. 05). Gut microbiota analysis revealed alterations in microbial community structure. At the phylum level, the abundance of Firmicutes, Actinobacteriota, Unclassified, and Campylobacterota decreased significantly(P<0. 01, P<0. 05), while that of Bacteroidota, Verrucomicrobiota, Patescibacteria, and Cyanobacteria increased significantly(P<0. 01, P<0. 05). At the genus level, abundances of certain genera, such as Muribaculaceae _ unclassified and Lactobacillus, were significantly decreased ( P<0. 05), while Ruminococcus, Clostridia _ UCG-014 _ unclassified,Akkermansia, Firmicutes_unclassified, and Monoglobus significantly increased(P<0. 01, P<0. 05). Compared with the model group, the CGRP inhibitor, Flunarizine group, and Xiongmatang active ingredients dose-dependently reversed these depressive-like behavioral changes and cognitive impairments, and significantly lowered serum levels of CGRP and NO. The active ingredients of Xiongmatang treatment also modulated intestinal microbial diversity; α-diversity assays showed increased richness and evenness, while β-diversity revealed that the microbial community structure of Xiongmatang-treated rats closely resembled that of the control group. At both phylum and genus levels,the alterations in microbiota composition exhibited trends opposite to those seen in the model group. Conclusions The active ingredients of Xiongmatang may prevent and treat migraines in rats through gut microbiota regulation.

Abstract: Objective To investigate the effects and mechanism of homocysteine (Hcy)-regulated FOXO3amediated mitochondrial damage in metabolic dysfunction-associated fatty liver disease (MAFLD). Methods Sixweek-old Cbs ^{+ / -} mice (n= 12) were divided randomly into two groups and fed a normal diet group (ND group) or a high-methionine diet group (HMD group), respectively, for 12 weeks (n = 6 mice per group). The inhibition rate of hepatocytes after treatment with different concentrations(0、50、100、150 μmol / L) of Hcy was detected by the Cell Counting Kit-8 Kit. NCTC1469 normal mouse hepatocytes were divided into the following groups: Control group, Hcy intervention group (Hcy group, 100 μmol / L Hcy), negative control (NC) small interfering ( si) RNA-transfected group ( si-NC group), FOXO3a siRNA-transfected group ( si-FOXO3a group), NC siRNA-transfected with Hcy intervention group ( Hcy + si-NC group), and FOXO3a siRNA-transfected with Hcy intervention group ( Hcy + siFOXO3a group). Liver tissue injury was observed by HE staining and the distribution and accumulation of lipid droplets in hepatocytes was detected by Oil Red O staining. Total cholesterol ( TC) and triglycerides ( TG) were analyzed to indicate the lipid metabolite contents of the cells. FOXO3a protein expression in liver tissues (ND group and HMD group) and liver cells (Control group and Hcy group) were detected by Western blot. Reactive oxygen species (ROS) were measured to indicate the degree of oxidative stress in cells. Mitochondrial membrane potential was detected using JC-1 and morphological changes in mitochondria were observed using Mito-tracker. Changes in mtDNA expression were detected by quantitative reverse transcription-polymerase chain reaction. Results Liver tissue structure was disordered in the HMD group compared with the ND group, hepatocytes were enlarged, the cytoplasm was loose and lightly stained, and a large number of vacuoles and lipid droplets were observed in the liver cells. The number of Oil Red O-positive lipid droplets was increased in the Hcy group compared with the Control group, and TC and TG levels were increased( P<0. 001). Expression levels of FOXO3a protein were significantly increased in the HMD group and Hcy group compared with the ND group and Control group(P<0. 05). Intracellular ROS levels were decreased in the Hcy+si-FOXO3a group compared with the Hcy+si-NC group, and JC-1 monomer,mitochondrial fragmentation, mtDNA expression level, the number of Oil Red O-positive lipid droplets, and TC level and TG level were also all decreased(P<0. 01, P<0. 001). Conclusions FOXO3a plays an important promoting role in lipid metabolic disorders of MAFLD caused by Hcy by regulating mitochondrial damage.

Abstract: Objective To investigate whether genistein alleviates alcoholic fatty liver disease (AFLD) by regulating sirtuin1 (SIRT1) / sirtuin3 (SIRT3) / forkhead box protein O1 (FOXO1) signaling pathway. Methods A HepG2 AFLD model was induced using 100 μmol / L oleic acid combined with 150 mmol / L 95% ethanol. The experiment was divided into 16 groups, including control, model, genistein, and resveratrol groups, SIRT1 gene silencing control + model, genistein, and resveratrol groups (C-shSIRT1, M-shSIRT1, G-shSIRT1, and R-shSIRT1,respectively), SIRT3 gene silencing control + model, genistein, and resveratrol groups (C-shSIRT3, M-shSIRT3, GshSIRT3, and R-shSIRT3, respectively), and SIRT1 / SIRT3 dual gene silencing control + model, genistein, and resveratrol groups (C-shSIRT1 / 3, M-shSIRT1 / 3, G-shSIRT1 / 3, and R-shSIRT1 / 3, respectively). Cellular steatosis was analyzed through Oil Red O staining and measurements of triglyceride, total cholesterol, and free fatty acid levels.Intracellular levels of tumor necrosis factor-α and interleukins 6 and 1β were determined by enzyme-linked immunosorbent assay. Western blot was used to detect protein expression levels of SIRT1, SIRT3, and FOXO1, and their interactions were analyzed by co-immunoprecipitation. Results Genistein significantly reduced lipid deposition and inflammatory responses in HepG2 AFLD model cells ( P<0. 05). Compared with the control group, protein expression of SIRT1, SIRT3, and FOXO1 was significantly decreased in the model group (P<0. 01). Compared with the model group, the genistein group showed significantly increased protein expression of SIRT1, SIRT3, and FOXO1 (P<0. 05). Co-immunoprecipitation result showed that SIRT1, SIRT3 and FOXO1 interacted. Genistein significantly reduced cellular steatosis after either SIRT1 or SIRT3 gene silencing, but its anti-AFLD effect was attenuated when both genes were simultaneously silenced. Compared with the C-shSIRT1 group, FOXO1 expression was significantly increased in the M-shSIRT1 group ( P<0. 01). Compared with the M-shSIRT1 group, FOXO1 expression was significantly decreased in the G-shSIRT1 group (P<0. 01). Compared with the C-shSIRT3 group, FOXO1 expression was significantly decreased in the M-shSIRT3 group ( P<0. 01). Compared with the M-shSIRT3 group, FOXO1 expression was significantly increased in the G-shSIRT3 group (P<0. 01). Compared with the C-shSIRT1 / 3 group,FOXO1 expression was significantly decreased in the M-shSIRT1 / 3 group (P<0. 01); FOXO1 expression levels were similar between the M-shSIRT1 / 3 and G-shSIRT1 / 3 groups (0. 05). Conclusions Genistein ameliorates lipid metabolism and suppresses inflammatory response in HepG2 AFLD cells by regulating SIRT1 / SIRT3 / FOXO1 signaling pathway, with the SIRT3 / FOXO1 axis playing a particularly crucial role.

Abstract: Objective To investigate the effects of time-restricted feeding (TRF) on improving metabolicassociated steatohepatitis (MASH) and the underlying molecular mechanisms involved. Methods ( 1) A MASH model was established in C57BL / 6J mice using a high-fat, high-cholesterol diet. Twenty-four mice were randomly assigned to normal control ( NC), normal time-restricted feeding ( NT), model ( M), and model time-restricted feeding (MT) groups ( n=6 per group). Mice were anesthetized and weighed after 14 weeks, and serum samples were collected. Serum levels of total cholesterol ( TC), triglycerides ( TG), aspartate aminotransferase ( AST),alanine aminotransferase (ALT), malondialdehyde (MDA), and ferrous ions ( Fe²⁺) were measured. Livers were harvested to calculate the liver index. Oil Red O, hematoxylin-eosin (HE), and Masson’ s trichrome staining were used to evaluate hepatic steatosis degree, inflammatory infiltration, and fibrosis. Protein expression levels of silent information regulator 1 ( Sirt1), nuclear factor E2-related factor 2 ( Nrf2), acyl-coA synthetase long-chain family member 4( ACSL4), transferrin receptor 1 ( TfR1), solute carrier family 7 member 11 ( SLC7A11), glutathione peroxidase 4 (GPX4), and tumor necrosis factor alpha (TNF-α) were detected by Western blot. (2) Additionally,an in vitro MASH model was established in human HepG2 cells using oleic acid and cholesterol stimulation, and a fasting model was established with serum deprivation. Cells were divided into Control, serum-deprived (FBS-), M, and M + FBS- groups. The ferrostatin-1 ( Fer-1) ferroptosis inhibitor was employed to investigate the relationship between ferroptosis and MASH/ TRF. Sirt1 activity was inhibited using EX-527 to investigate the relationship between Sirt1 and Nrf2-mediated ferroptosis. Lipid accumulation in hepatocytes was observed with Oil Red O staining. HepG2 TC, TG, ALT, and AST levels were measured using kits. Western blot analysis was used to assess Sirt1, Nrf2,TfR1, ACSL4, SLC7A11, GPX4, and TNF-α protein expression levels in HepG2 cells. Results (1) Compared with MASH mice, TRF significantly reduced body weight and TC, TG, ALT, AST, MDA, and Fe²⁺ serum levels (P<0. 01). Liver Fe²⁺ levels and TNF-α expression were also decreased (P<0. 01), while hepatic steatosis and fibrosis were improved. Western blot analysis revealed that TRF intervention significantly increased Sirt1, Nrf2, SLC7A11,and GPX4 protein levels (P<0. 01) while decreasing those of TfR1 and ACSL4 in the livers of MASH mice (P<0. 01). (2) Compared with the M group, serum deprivation intervention reduced TC, TG, ALT, AST, MDA, and TNF-α levels in oleic acid-cholesterol-induced HepG2 cells ( P<0. 01), effectively reducing the number of lipid droplets. Western blot analysis indicated that serum deprivation elevated Sirt1, Nrf2, SLC7A11, and GPX4 protein levels ( P<0. 01) while decreasing those of TfR1 and ACSL4 ( P<0. 01). SLC7A11 and GPX4 protein levels increased following Fer-1 intervention (P<0. 01), while those of TfR1 and ACSL4 decreased (P<0. 01). Following EX-527 intervention, Sirt1, Nrf2, SLC7A11, and GPX4 protein levels decreased (P<0. 05 or P<0. 01), while TfR1 and ACSL4 levels significantly increased (P<0. 01), attenuating the ameliorative effects of serum deprivation on fat accumulation and injury in the M group ( P<0. 05 or P<0. 01). Conclusions TRF may improve metabolicassociated fatty liver disease by inhibiting ferroptosis, with its protective mechanism potentially involving Sirt1 / Nrf2 pathway mediation.

Abstract: Objective To investigate the effects and modes of action of combined black carbon (BC) and palmitic acid ( PA) exposure on mouse spermatogonia GC-1, as well as the role of the nuclear factor erythroid 2-related factor (NRF2) pathway in this process. Methods Control, PA, BC, and combined treatment groups were established. Mouse spermatogonia GC-1 cells were treated with PA and BC for 24 h. Cell viability was assessed using Cell Counting Kit-8 ( CCK-8) detection. Reverse-transcription quantitative PCR ( RT-qPCR) was used to detect mRNA expression levels of antioxidant stress-related genes Nfe2l2, Kelch-like erythroid cell-derived protein with CNC homology(ECH)-related protein 1 (Keap1), catalase (Cat), heme oxygenase-1 (Hmox1), quinone oxidoreductase1 (Nqo1), glutamyl cysteine ligase ( Gclc), autophagy-related genes ( Lc3b and Sqstm1), and ferroptosis-related genes glutathione peroxidase 4 (Gpx4). Lipid oxidation (MDA) and reduced glutathione (GSH) were determined using colorimetry. Western blot was used to detect NRF2 protein expression levels. Results With the increase in exposure concentration, the inhibitory effect of PA and BC on GC-1 proliferation was enhanced; half maximal inhibitory concentration(IC₅₀) values of PA and BC on GC-1 cells after 24 h were 320 μmol / L and 560 μg / mL,respectively. When PA was combined with BC, its IC₅₀ for GC-1 cells was lower than that of the single-agent group,indicating synergy. RT-qPCR showed that after 24 h of PA and BC exposure, both alone and in combination, the expression of Nfe2l2, Keap1, Cat, Hmox1, Nqo1, Gclc, Gpx4, Lc3b, and Sqstm1 differed compared with the control group (P<0. 05). MDA content in each experimental group was higher than that in the control group (P<0. 05),while GSH content was lower (P<0. 05). Western blot showed that NRF2 protein expression increased with increasing PA and BC concentrations compared with the control ( P<0. 05). Conclusions PA and BC both inhibited spermatogonia proliferation, and can synergize when present together to enhance cytotoxicity. When low-level PA and BC are combined and applied to spermatogonia, NRF2 signaling is activated, changing expression levels of oxidative stress, ferroptosis, and autophagy-related genes; this causes cells to react to oxidative stress and suggests that the NRF2 pathway may be involved in regulating spermatogonia damage caused by combined exposure to PA and BC.

Abstract: Objective To establish and compare C57BL / 6J mouse models of alopecia areata induced by imiquimod (IMQ) and cyclophosphamide (CTX). Methods A total of 104 C57BL / 6J mice were divided into an IMQ group (5% 0. 05 g IMQ applied to the head / back, 4 times a week, for 4 weeks), a CTX group (intraperitoneal injection of 3 mg / 20 g CTX after hair removal), and a control group treated with Vaseline (0. 05 g) or hair removal alone in the corresponding area. Body weight and hair changes were monitored continuously during the modeling process. Changes in skin hair follicles and epidermal thickness were observed by hematoxylin-eosin staining.Expression levels of interferon-γ (IFN-γ), interleukin-15 (IL-15), and tumor necrosis factor-α (TNF-α) in mouse head and back skin lesions and serum were detected by enzyme-linked immunosorbent assay. Results The IMQ group cycle was 4 weeks, and a patchy bare area about 1 cm × 1 cm developed on the head and back skin in week 4,accompanied by a small amount of scales. The CTX modeling cycle was 14 days, and the hair on the head and back lesions fell off 5 days after intraperitoneal CTX injection, and the skin appeared dark gray. Histopathology showed significant changes in hair follicles between the two model groups compared with the control group, with greater thickening of the epidermis in the IMQ group. Both IMQ and CTX significantly increased IFN-γ, IL-15, and TNF-α levels in skin and serum(P< 0. 0001), with a more pronounced increase in inflammatory factors in the IMQ group (P<0. 0001, P<0. 001, P<0. 01). Conclusions Both IMQ and CTX can successfully induce alopecia areata on the head and back in C57BL / 6J mice. Compared with IMQ, CTX modeling has the advantages of shorter modeling time,higher survival rate, and higher modeling rate, creating a relatively stable animal model of alopecia areata.

Abstract: Objective This study established an indirect enzyme-linked immunosorbent assay-based serological diagnostic method for Lyme disease in mice, using whole-cell antigens of Borrelia garinii strain SZ,providing standardized technical support for the laboratory diagnosis and epidemiological surveillance of Lyme disease. Methods Experimental conditions were systematically optimized to determine the optimal antigen coating concentration, serum dilution ratio, and enzyme-labeled secondary antibody concentration. A mouse infection model was established, and sera were collected at different time points to analyze antibody dynamics. Cross-reactivity with Borrelia burgdorferi strain B31 and Borrelia afzelii strain BO23 was evaluated. Results Through systematic optimization of experimental conditions, the optimal reaction system was determined to be an antigen coating concentration of 0. 2 μg / μL, serum dilution ratio of 1 ∶ 200, and enzyme-labeled secondary antibody concentration of 1 ∶ 2000. This method ensured high sensitivity ( optical density value > 0. 8) while significantly reducing antigen consumption. Antibody dynamic analysis revealed that serum antibody levels in infected mice peaked between 12~25 days post-inoculation, with a specificity antibody ratio threshold of 41. 7% to distinguish positive and negative samples. Cross-reactivity between Borrelia garinii and Borrelia burgdorferi (B31) as well as Borrelia afzelii (BO23) was also evaluated, indicating certain cross-reactivity with BO23 but no significant cross-reactivity with B31. Conclusions The result demonstrated that this method is simple, cost-effective, and suitable for primary laboratories and small-scale screening, providing a reliable standardized method for Lyme disease laboratory diagnosis and epidemiological surveillance.

Abstract:Acid-sensing ion channel 1a (ASIC1a) is a proton-gated cation channel that is widely expressed in the central nervous system, and is involved in various physiological and pathological processes by regulating calcium and sodium influx, synaptic plasticity, and reward effects. Recent studies have demonstrated that ASIC1a plays a pivotal role in drug abuse, by modulating neuronal excitability, synaptic plasticity, and reward circuitry. ASIC1a has thus emerged as a key molecule in the mechanisms of drug addiction and as a potential therapeutic target. This review systematically summarizes the molecular characteristics of ASIC1a, its neuroregulatory mechanisms, and its regulatory role in drug abuse, aiming to provide novel targets for elucidating the mechanisms of drug addiction and for the development of new strategies for addiction withdrawal therapy.

Abstract:Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease, characterized by pathological changes including decreased glomerular filtration rate and proteinuria. As a key component of the glomerular filtration barrier, podocyte injury is closely associated with the progression of DKD. Recent studies revealed that mitochondrial dysfunction plays a central role in podocyte injury in DKD, primarily manifested as enhanced mitochondrial oxidative stress, defective autophagy, and fission / fusion imbalance. These alterations lead to the excessive production of reactive oxygen species and inflammatory factors, thereby accelerating podocyte apoptosis.Multiple signaling pathways, including NADPH oxidase 4 / transient receptor potential cation channel subfamily C member 6, transforming growth factor β1 / SMAD, AMP-activated protein kinase / peroxisome proliferator-activated receptor gamma coactivator 1α, and PTEN induced kinase 1 / Parkin, can intervene in mitochondrial damage-induced podocyte apoptosis, while DKD is exacerbated by the dysregulation of genes related to podocyte mitochondrial function. This review systematically considers the critical roles of relevant signaling pathways and mitochondrial damage in mediating podocyte mitochondrial injury during DKD progression, aiming to provide new theoretical foundations and therapeutic targets for DKD prevention and treatment. We also explore the potential of traditional Chinese medicine targeting podocyte mitochondria as a strategy to delay DKD progression.

Abstract:Traumatic brain injury (TBI) is a leading global cause of mortality and neurological dysfunction.Its pathological process involves both primary and secondary injuries. External forces directly cause vascular rupture and axonal disruption, leading to cerebral hemorrhage and cellular damage; the secondary phase further exacerbates the injury through mechanisms such as neuroinflammation, neuronal degeneration, and mitochondrial dysfunction.Current clinical strategies for TBI management include surgery, pharmacological interventions, hyperbaric oxygen therapy, nutritional support, and hypothermia. While these approaches can alleviate certain symptoms, their efficacy in improving long-term neurological outcomes remains limited. Tissue engineering has provided new strategies for TBI treatment. The application of biomaterials such as hydrogels, electrospun nanofibers, and nanomaterial-based drug delivery systems can create biomimetic microenvironments, overcome the delivery limitations imposed by the bloodbrain barrier, and enable coordinated multilevel neural repair. This review aims to summarize recent advances in tissue engineering strategies for TBI treatment, analyze their therapeutic effects and underlying mechanisms, and propose new directions for future research.

Abstract:Post-stroke cognitive impairment ( PSCI) is a common and debilitating complication following stroke that involves complex mechanisms such as neuroinflammation, neurotransmitter imbalance, and impaired neural plasticity. Recently, the vagus nerve (VN)-mediated gut-brain axis (GBA), a vital bidirectional communication pathway between the central nervous system and the gut, has gained increasing attention for its pivotal role in PSCI onset and recovery. The VN modulates gut microbiota homeostasis, intestinal barrier integrity, and immune responses, indirectly affecting central nervous system inflammation and neural plasticity. Stroke can disrupt VN signaling, resulting in gut microbiota dysbiosis and altered metabolite production, which further trigger central inflammatory responses and worsen cognitive dysfunction. This review synthesizes current evidence on the mechanisms of the VN-GBA in PSCI and their interconnected relationships, and explores targeted intervention strategies that may offer promising therapeutic avenues for managing PSCI to contribute to its clinical prevention and treatment.

Abstract:The global incidence of autism spectrum disorder ( ASD) shows a significant upward trend.Analysis of its pathological mechanism and development of intervention strategies are major challenges in the field of neurodevelopmental disorders. Exercise intervention can significantly alleviate social disorders, cognitive deficits, and stereotyped behaviors in individuals with ASD, but the neurobiological mechanisms of these effects need to be systematically elucidated. The striatum has a pivotal role in the cortical basal ganglia loop and is closely associated with ASD behavior and functional abnormalities and this review focuses on the key role of striatal remodeling in exercise intervention. Integration of evidence from animal experiments and clinical research has shown the striatum to be involved in exercise-mediated improvement in autism behavior. These observations include strengthening the morphological structure of striatal regions, improving the expression of striatal neurotrophic factors, regulating the transmission of dopamine signals in striatal regions, and enhancing the transmission of cortico-striatal glutamatergic signals. By exploring the potential role of the striatum in improving autism behavior through exercise, this multi-scale analysis framework aims to elucidate the potential role of “striatal motor remodeling for ASD behavior improvement”and to provide new ideas for exercise-based improvement of autism behavior.