Objective: To explore the developmental trajectories of depression in children and adolescents and their association with family types, and to analyze the role of being an only child in the context, so as to provide a basis for early identification of mental health issues in children and adolescents. Methods: The study was a secondary analysis based on the existing database of the Jiangsu Provincial Student Common Diseases and Health Influencing Factors Monitoring and Intervention Project. A total of 11 502 students who had completed at least two measurements using the Chinese version of the Center for Epidemiologic Studies Depression Scale (CES-D) between 2022 and 2024, and had complete information on family type, gender, and age, were selected as the study subjects. Latent class trajectory modeling was used to identify depression developmental trajectories. Multinomial Logistic regression was applied to analyze the association between family type and depression developmental trajectories, and the interaction effect of family type and being an only child was tested. Results: Three types of depression developmental trajectories were identified among children and adolescents: low stable type (91.3%, 10 504 students), moderate rising type (4.3%, 500 students), and high declining type (4.3%, 498 students). Significant differences were observed among the different trajectory groups in terms of gender, age, parental education level, family type, baseline CES-D score, and baseline school type ( χ 2/H=17.48, 139.97, 19.72 , 30.77, 1 081.35, 220.81, all P <0.05). Multinomial Logistic regression analysis showed that, using the low stable type as the reference trajectory group and the nuclear family as the reference family type, after adjusting for confounding factors such as gender, age, and parental education level, single parent families ( OR=1.87, 95%CI= 1.16-3.03) and grandparent headed families ( OR=1.83, 95%CI =1.04-3.21) were significantly associated with the high declining type trajectory (both P <0.05). No significant association was found between family type and the moderate rising type trajectory (all P >0.05). The interaction effect between family type and being an only child was not statistically significant ( LRT=7.71, df=8, P =0.46). Conclusions Depressive symptoms in children and adolescents show heterogeneous developmental patterns during school age. Children and adolescents from single parent and intergenerational families are more likely to follow the high decreasing trajectory.

Objective: To understand the current status of short video addiction among vocational nursing students in higher vocational colleges (hereinafter referred to as "nursing students") and its related factors, so as to provide a reference for formulating online education programs in colleges. Methods: From March to May 2025, a stratified random sample of 2 223 nursing students from four vocational colleges in Henan Province was selected. Short Video Addiction Scale for College Students, Short form Egna Minnen av Barndoms Uppfostran for Chinese, Peer Rejection Scale, and University of California at Los Angels Loneliness Scale were used for investigation. Chi square test and multivariate Logistic regression analysis were used to explore the related factors of short video addiction among nursing students. Results: The detection rate of short video addiction of higher vocational nursing students was 26.95%, and the scores for avoidance, loss of control, inefficiency and withdrawal were (8.05±2.97) (10.24±3.09) (4.99±1.88) and (11.97±4.10), respectively. Multivariate Logistic regression analysis showed that sophomore year 2 ( OR=1.83, 95%CI =1.39-2.40), higher maternal education level (secondary school/vocational college: OR =1.34, 95% CI =1.06-1.68; college/undergraduate: OR =1.38, 95% CI =1.05-1.82), paternal overprotection ( OR=1.59, 95%CI =1.27-2.00), high peer rejection ( OR=1.40, 95%CI =1.19-1.66), and strong loneliness ( OR=1.57, 95%CI =1.07-2.28) were associated with a higher risk of short video addiction among nursing students (all P <0.05). Paternal affectionate and warm rearing style ( OR=0.82, 95%CI = 0.71- 0.95) was associated with a lower risk of short video addiction ( P <0.05). Conclusions The detection rate of short video addiction among nursing students is relatively high. Short video addiction is related to the nursing students grade, maternal education level, paternal overprotection and affectionate rearing style, peer rejection, and loneliness.

ObjectiveTo evaluate the efficacy and safety of Janus kinase （JAK） inhibitors combined with Chinese herbal medicine （CHM） in treating rheumatoid arthritis （RA）. MethodsClinical data from 169 RA patients were retrospectively collected. Among them， 71 cases received JAK inhibitors as the control group， while 98 cases received JAK inhibitors plus CHM as the observation group， both treated for 24 weeks. The rheumatoid factor （RF）， cyclic citic peptide antibody （anti-CCP）， erythrocyte sedimentation rate （ESR）， C-reactive protein （CRP）， and white blood cell count （WBC） were recorded before and after treatment. Databases including CNKI， Wanfang， VIP， PubMed and Web of Science were searched from inception till August 31st， 2025 for randomized controlled trials （RCTs） on the combined use of JAK inhibitors and CHM for RA. The methodological quality of the included studies was evaluated using the risk of bias assessment tool. Meta-analyses were performed for RF， anti-CCP， ESR， CRP， 28-joint disease activity score （DAS28）， overall clinical effective rate， and incidence of adverse events. Sensitivity analysis were also performed. ResultsThe retrospective study demonstrated that after treatment， ESR， CRP， and anti-CCP levels decreased in the observation group， while ESR and CRP levels decreased in the control group （P＜0.05）. Moreover， ESR and RF levels in the observation group were lower than those in the control group （P＜0.05）. A total of 9 RCTs involving 770 patients were included in the meta-analysis. The results indicated that the JAK inhibitors plus CHM group was superior to the JAK inhibitors group in reducing RF （MD=-8.97， 95%CI -15.01 to -2.94， P=0.004）， CRP （MD=-3.34， 95%CI -3.82 to -2.86， P＜0.001）， ESR （MD=-5.33， 95%CI -7.98 to -2.69， P＜0.001）， and DAS28 score （MD=-0.54， 95%CI -0.74 to -0.34， P＜0.001）， as well as in improving the overall clinical effective rate （OR=4.53， 95%CI 2.55 to 8.03， P＜0.001）. No statistically significant differences were observed between groups in anti-CCP levels （SMD=-2.08， 95%CI -4.41 to 0.24， P=0.080） or incidence of adverse events （OR=0.93， 95%CI 0.55 to 1.57， P=0.790）. ConclusionThe combination of JAK inhibitors and CHM demonstrates remarkable efficacy in treating RA， contributing to improved disease activity and reduced inflammatory markers with a favorable safety profile.

Objective To establish quality evaluation method of Andrographis paniculata standard decoction by UPLC. Methods 21 batches of Andrographis paniculata standard decoctions were prepared according to the standardization method of TCM decoction pieces. The UPLC characteristic chromatograms analysis method was established. With andrographolide as a reference, quantitative analysis of multi-components by single marker （QAMS） was established for new neoandrographolide, 14 deoxyandrographolide and dehydrated andrographolide. The results were compared with the external standard method （ESM） to determine the accuracy of the method. Results Similarity Evaluation System for Chromatographic Fingerprint of TCM （2012 edition） was used to analyze and compare the characteristic chromatograms, and seven common peaks were determined and five were identified including luteolin-7-O-β-D-glucuronide, andrographolide, neoandrographolide, 14-deoxyandrographolide and dehydroandrographolide. The RSDs of content results of each component by QAMS and ESM were all within 3%. Conclusion The determination method was reliable and accurate, which could be used to reflect the intrinsic quality of Andrographis paniculata standard decoction comprehensively and provide the basis for the quality evaluation of Andrographis paniculata formula granules and other preparations.

Intervertebral disc degeneration (IVDD) is the predominant pathological contributor to chronic low back pain, a pervasive musculoskeletal condition affecting over 630 million people globally and imposing tremendous socioeconomic and public health burdens. The etiopathogenesis of IVDD is remarkably complex and multifactorial, involving intricate crosstalk among chronic inflammatory responses, extracellular matrix (ECM) catabolism, cellular senescence, aberrant programmed cell death (including apoptosis, pyroptosis, and ferroptosis), mitochondrial dysfunction, and oxidative damage. Compelling evidence indicates that the inflammatory microenvironment acts as a decisive driving force throughout the entire degenerative course of IVDD. Among the diverse inflammatory mediators, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) serve as core pro-inflammatory cytokines that initiate and perpetuate the degenerative cascade. These two pivotal cytokines collectively activate an array of canonical intracellular signaling pathways, including nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) inflammasome, and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) cascade. Such interconnected signaling networks trigger a self-reinforcing positive feedback loop, which exacerbates inflammatory reactions, disrupts the anabolic-catabolic homeostasis of the ECM, promotes oxidative stress and mitochondrial injury, induces multiple forms of disc cell death, and ultimately leads to progressive structural collapse and functional deterioration of the intervertebral disc. Conventional therapeutic strategies, dominated by nonsteroidal anti-inflammatory drugs and surgical interventions, are limited by systemic adverse reactions, suboptimal long-term efficacy, and the risk of adjacent segment degeneration. In contrast, traditional Chinese medicine (TCM) exhibits prominent advantages in the prevention and treatment of IVDD by virtue of its holistic regulation, syndrome differentiation, and multi-component, multi-target, multi-pathway pharmacological properties. This review systematically elucidates the molecular mechanisms by which inflammation-associated signaling pathways modulate disc cell fate and ECM metabolic homeostasis, and comprehensively summarizes the experimental progress over the past five years on TCM monomers and compound formulas for intervening in IVDD. Accumulating studies have confirmed that numerous natural active ingredients isolated from herbal medicines (ferulic acid, mangiferin, paeonol, astragaloside IV) and representative TCM compound prescriptions (Bushen Huoxue Formula, Shensuitongzhi Formula, Fuzi Decoction) exert synergistic protective effects by coordinately targeting core signaling hubs. These TCM agents demonstrate potent anti-inflammatory, antioxidant, anti-apoptotic, anti-pyroptotic, anti-ferroptotic, ECM-protective, and autophagy-regulating bioactivities, thereby effectively decelerating the pathological progression of IVDD. Despite remarkable progress, current investigations are still confronted by several critical limitations. Most studies are restricted to validating the regulatory effects of single TCM components on individual signaling pathways, leaving the systematic, dynamic, and synergistic mechanisms of TCM compound formulas within multi-pathway regulatory networks largely unexplored. Furthermore, clinical translation of TCM is severely hampered by the lack of efficient targeted drug delivery systems, unclear pharmacokinetic profiles, suboptimal local bioavailability, and incomplete long-term safety assessments. Therefore, future research should adopt an interdisciplinary paradigm integrating multi-omics technologies, artificial intelligence, organoid models, and organ-on-chip systems to systematically decipher the scientific basis of TCM against IVDD. Concurrently, the development of intelligent, site-specific delivery systems (hydrogels, nanoparticles, exosome-based carriers) is urgently needed to enhance the local accumulation and sustained release of TCM ingredients. By deepening mechanistic exploration and accelerating translational research, TCM is expected to evolve into safe, effective, and personalized precision therapeutic regimens for IVDD, offering novel and reliable solutions for the clinical management of chronic low back pain.

ObjectiveObesity, a global chronic metabolic disease, is closely associated with disruptions in lipid metabolism and gut microbiota. Current intervention strategies still have limitations in terms of safety and microecological regulation, necessitating the exploration of novel natural regulatory approaches. Based on the early pathological characteristics of obesity, this study innovatively employs a rectal delivery method alongside a high-fat diet (HFD)-induced obesity model to systematically evaluate the inhibitory effects, safety, and gut microbiota regulation mechanisms of leek-derived and konjac-derived extracellular vesicles on obesity development. By simulating early clinical intervention scenarios, this study aims to explore the preventive potential of plant-derived extracellular vesicles during the initial stages of obesity onset. MethodsExtracellular vesicles from leek and konjac were isolated using ultracentrifugation combined with density gradient centrifugation. Their nanoscale properties were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). Male C57BL/6J mice were randomly divided into four groups: normal control (NC), high-fat diet (HFD), leek-derived extracellular vesicles (LEVs), and konjac-derived extracellular vesicles (KEVs). Beginning simultaneously with HFD feeding, mice in the intervention groups received 20 g/L vesicles rectally every 3 d for 4 weeks. Body mass and body composition were monitored throughout. At endpoint, mouse serum, adipose tissue, and colonic contents were collected. Serum biochemical indices (lipid profile, liver and kidney function, cardiac markers) were assessed to evaluate safety and metabolic efficacy, while 16S rRNA sequencing was employed to analyze gut microbial structure and diversity. ResultsDLS, NTA, and TEM confirmed that both LEVs and KEVs exhibited typical cup-shaped nanostructures with average particle sizes of approximately 284 nm and 223 nm, respectively. LEVs and KEVs treatment significantly suppressed HFD-induced weight gain and elevation of body-fat percentage (P<0.05), and reduced accumulation of abdominal white and epididymal adipose tissue. Serological analyses showed that both vesicles lowered total cholesterol, triglycerides and LDL-cholesterol, and ameliorated liver enzyme profiles (ALT, AST), demonstrating lipid-metabolic regulation and hepatoprotective effects. No hepatic, renal or cardiac dysfunction was observed, indicating favorable safety. Gut microbiota analyses revealed that vesicle intervention partially restored HFD-depleted microbial diversity and reshaped community structure. Notably, LEVs markedly increased the relative abundance of the beneficial taxon Lachnospiraceae at the family level, which is known for producing short-chain fatty acids and enhancing intestinal barrier function. Furthermore, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) functional prediction suggested that LEVs and KEVs modulated gut microbial functions through distinct mechanisms: LEVs downregulated pathways related to ribosomes and DNA replication while enhancing xenobiotic degradation, whereas KEVs tended to upregulate energy metabolism and protein synthesis toward healthy levels. ConclusionRectally administered LEVs and KEVs exhibit excellent safety and pronounced metabolic benefits during the early phase of obesity, suppressing weight gain, correcting lipid dysregulation, and exerting effects via modulation of gut microbial composition and function. This study provides systematic experimental evidence supporting plant-derived exosome-like vesicles as an early intervention strategy against obesity.

ObjectiveTranscranial magneto-acoustic stimulation (TMAS) is an emerging non-invasive neuromodulation technique that may provide a novel non-pharmacological intervention strategy for Parkinson's disease (PD). PD is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc), leading to motor impairments such as bradykinesia, tremor, and rigidity. Increasing evidence indicates that mitochondrial dysfunction and impaired mitochondrial quality control are central mechanisms underlying dopaminergic neuronal loss. In particular, abnormalities in mitophagy and mitochondrial fission-fusion balance contribute substantially to oxidative stress, energy metabolic failure, and neuronal injury. At present, most clinical treatments for PD mainly alleviate symptoms but do not effectively halt disease progression. Therefore, exploring new interventions targeting the core pathological mechanisms is of considerable significance. This study aims to investigate whether TMAS can improve neural damage and motor dysfunction in PD mice by regulating mitophagy and the fission/fusion dynamic balance, thereby providing theoretical and experimental support for its application in PD treatment. MethodsMale C57BL/6 mice were used in this study. A PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days. After model induction, mice in the intervention group received TMAS once daily for 14 consecutive days, whereas the corresponding control group received sham stimulation. The stimulation target was positioned over the primary motor cortex (M1). Motor performance was evaluated using the pole test and the open-field test. To verify the activation effect of TMAS on the target cortical region, c-Fos immunohistochemistry was performed in the M1. To assess nigral dopaminergic neuronal injury, tyrosine hydroxylase (TH) immunohistochemistry was used to quantify TH-positive neurons in the SNc. Mitochondrial function was evaluated by measuring reactive oxygen species (ROS) levels and adenosine triphosphate (ATP) content in the SNc. Western blot was further performed to determine the expression of mitophagy-related proteins, including PINK1, Parkin, LC3-II, and p62, as well as mitochondrial dynamics-related proteins, including Drp1 and Opa1. ResultsTMAS significantly increased the number of c-Fos-positive cells in M1 (P<0.000 1), indicating effective activation of neurons in the targeted cortical region. Compared with the control group, MPTP-treated mice exhibited marked motor dysfunction, including a significant reduction in total distance traveled in the open-field test (P<0.000 1) and mean speed (P=0.000 1), as well as significant prolongation of turn time and total climbing time in the pole test (P<0.000 1). These behavioral impairments were accompanied by a substantial loss of TH-positive dopaminergic neurons in the SNc, whereas TMAS significantly increased TH-positive neuron survival (P<0.000 1). In parallel, MPTP induced a pronounced increase in ROS levels and a significant reduction in ATP content, indicating severe mitochondrial dysfunction and energy metabolism impairment (P<0.01). TMAS treatment significantly improved motor performance, as reflected by the reversal of MPTP-induced impairment in the open-field and pole tests, and significantly reduced ROS accumulation (P<0.01) while restoring ATP production (P<0.001). At the molecular level, MPTP markedly downregulated PINK1 and Parkin, decreased p62 expression, increased LC3-II accumulation, elevated Drp1 expression, and reduced Opa1 expression, whereas TMAS significantly reversed these abnormalities, suggesting restoration of mitophagy-related mitochondrial quality control and re-establishment of mitochondrial fission-fusion balance. Collectively, these findings indicate that TMAS ameliorates MPTP-induced neurotoxicity and restores mitochondrial homeostasis and energy metabolism. ConclusionTMAS effectively attenuates neural damage and improves motor dysfunction in MPTP-induced PD mice. Its neuroprotective effects are closely associated with multidimensional regulation of the mitochondrial quality control system, including restoration of PINK1/Parkin-mediated mitophagy and rebalancing of Drp1/Opa1-related mitochondrial dynamics. Rather than acting only as a symptomatic neuromodulatory intervention, TMAS may influence a key pathological axis of PD by improving mitochondrial homeostasis in SNc and protecting nigral dopaminergic neurons. These findings provide experimental evidence supporting TMAS as a promising non-invasive physical intervention for PD.

Intervertebral disc degeneration (IVDD) is the predominant pathological contributor to chronic low back pain, a pervasive musculoskeletal condition affecting over 630 million people globally and imposing tremendous socioeconomic and public health burdens. The etiopathogenesis of IVDD is remarkably complex and multifactorial, involving intricate crosstalk among chronic inflammatory responses, extracellular matrix (ECM) catabolism, cellular senescence, aberrant programmed cell death (including apoptosis, pyroptosis, and ferroptosis), mitochondrial dysfunction, and oxidative damage. Compelling evidence indicates that the inflammatory microenvironment acts as a decisive driving force throughout the entire degenerative course of IVDD. Among the diverse inflammatory mediators, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) serve as core pro-inflammatory cytokines that initiate and perpetuate the degenerative cascade. These two pivotal cytokines collectively activate an array of canonical intracellular signaling pathways, including nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) inflammasome, and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) cascade. Such interconnected signaling networks trigger a self-reinforcing positive feedback loop, which exacerbates inflammatory reactions, disrupts the anabolic-catabolic homeostasis of the ECM, promotes oxidative stress and mitochondrial injury, induces multiple forms of disc cell death, and ultimately leads to progressive structural collapse and functional deterioration of the intervertebral disc. Conventional therapeutic strategies, dominated by nonsteroidal anti-inflammatory drugs and surgical interventions, are limited by systemic adverse reactions, suboptimal long-term efficacy, and the risk of adjacent segment degeneration. In contrast, traditional Chinese medicine (TCM) exhibits prominent advantages in the prevention and treatment of IVDD by virtue of its holistic regulation, syndrome differentiation, and multi-component, multi-target, multi-pathway pharmacological properties. This review systematically elucidates the molecular mechanisms by which inflammation-associated signaling pathways modulate disc cell fate and ECM metabolic homeostasis, and comprehensively summarizes the experimental progress over the past five years on TCM monomers and compound formulas for intervening in IVDD. Accumulating studies have confirmed that numerous natural active ingredients isolated from herbal medicines (ferulic acid, mangiferin, paeonol, astragaloside IV) and representative TCM compound prescriptions (Bushen Huoxue Formula, Shensuitongzhi Formula, Fuzi Decoction) exert synergistic protective effects by coordinately targeting core signaling hubs. These TCM agents demonstrate potent anti-inflammatory, antioxidant, anti-apoptotic, anti-pyroptotic, anti-ferroptotic, ECM-protective, and autophagy-regulating bioactivities, thereby effectively decelerating the pathological progression of IVDD. Despite remarkable progress, current investigations are still confronted by several critical limitations. Most studies are restricted to validating the regulatory effects of single TCM components on individual signaling pathways, leaving the systematic, dynamic, and synergistic mechanisms of TCM compound formulas within multi-pathway regulatory networks largely unexplored. Furthermore, clinical translation of TCM is severely hampered by the lack of efficient targeted drug delivery systems, unclear pharmacokinetic profiles, suboptimal local bioavailability, and incomplete long-term safety assessments. Therefore, future research should adopt an interdisciplinary paradigm integrating multi-omics technologies, artificial intelligence, organoid models, and organ-on-chip systems to systematically decipher the scientific basis of TCM against IVDD. Concurrently, the development of intelligent, site-specific delivery systems (hydrogels, nanoparticles, exosome-based carriers) is urgently needed to enhance the local accumulation and sustained release of TCM ingredients. By deepening mechanistic exploration and accelerating translational research, TCM is expected to evolve into safe, effective, and personalized precision therapeutic regimens for IVDD, offering novel and reliable solutions for the clinical management of chronic low back pain.

ObjectiveObesity, a global chronic metabolic disease, is closely associated with disruptions in lipid metabolism and gut microbiota. Current intervention strategies still have limitations in terms of safety and microecological regulation, necessitating the exploration of novel natural regulatory approaches. Based on the early pathological characteristics of obesity, this study innovatively employs a rectal delivery method alongside a high-fat diet (HFD)-induced obesity model to systematically evaluate the inhibitory effects, safety, and gut microbiota regulation mechanisms of leek-derived and konjac-derived extracellular vesicles on obesity development. By simulating early clinical intervention scenarios, this study aims to explore the preventive potential of plant-derived extracellular vesicles during the initial stages of obesity onset. MethodsExtracellular vesicles from leek and konjac were isolated using ultracentrifugation combined with density gradient centrifugation. Their nanoscale properties were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). Male C57BL/6J mice were randomly divided into four groups: normal control (NC), high-fat diet (HFD), leek-derived extracellular vesicles (LEVs), and konjac-derived extracellular vesicles (KEVs). Beginning simultaneously with HFD feeding, mice in the intervention groups received 20 g/L vesicles rectally every 3 d for 4 weeks. Body mass and body composition were monitored throughout. At endpoint, mouse serum, adipose tissue, and colonic contents were collected. Serum biochemical indices (lipid profile, liver and kidney function, cardiac markers) were assessed to evaluate safety and metabolic efficacy, while 16S rRNA sequencing was employed to analyze gut microbial structure and diversity. ResultsDLS, NTA, and TEM confirmed that both LEVs and KEVs exhibited typical cup-shaped nanostructures with average particle sizes of approximately 284 nm and 223 nm, respectively. LEVs and KEVs treatment significantly suppressed HFD-induced weight gain and elevation of body-fat percentage (P<0.05), and reduced accumulation of abdominal white and epididymal adipose tissue. Serological analyses showed that both vesicles lowered total cholesterol, triglycerides and LDL-cholesterol, and ameliorated liver enzyme profiles (ALT, AST), demonstrating lipid-metabolic regulation and hepatoprotective effects. No hepatic, renal or cardiac dysfunction was observed, indicating favorable safety. Gut microbiota analyses revealed that vesicle intervention partially restored HFD-depleted microbial diversity and reshaped community structure. Notably, LEVs markedly increased the relative abundance of the beneficial taxon Lachnospiraceae at the family level, which is known for producing short-chain fatty acids and enhancing intestinal barrier function. Furthermore, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) functional prediction suggested that LEVs and KEVs modulated gut microbial functions through distinct mechanisms: LEVs downregulated pathways related to ribosomes and DNA replication while enhancing xenobiotic degradation, whereas KEVs tended to upregulate energy metabolism and protein synthesis toward healthy levels. ConclusionRectally administered LEVs and KEVs exhibit excellent safety and pronounced metabolic benefits during the early phase of obesity, suppressing weight gain, correcting lipid dysregulation, and exerting effects via modulation of gut microbial composition and function. This study provides systematic experimental evidence supporting plant-derived exosome-like vesicles as an early intervention strategy against obesity.

ObjectiveTranscranial magneto-acoustic stimulation (TMAS) is an emerging non-invasive neuromodulation technique that may provide a novel non-pharmacological intervention strategy for Parkinson's disease (PD). PD is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc), leading to motor impairments such as bradykinesia, tremor, and rigidity. Increasing evidence indicates that mitochondrial dysfunction and impaired mitochondrial quality control are central mechanisms underlying dopaminergic neuronal loss. In particular, abnormalities in mitophagy and mitochondrial fission-fusion balance contribute substantially to oxidative stress, energy metabolic failure, and neuronal injury. At present, most clinical treatments for PD mainly alleviate symptoms but do not effectively halt disease progression. Therefore, exploring new interventions targeting the core pathological mechanisms is of considerable significance. This study aims to investigate whether TMAS can improve neural damage and motor dysfunction in PD mice by regulating mitophagy and the fission/fusion dynamic balance, thereby providing theoretical and experimental support for its application in PD treatment. MethodsMale C57BL/6 mice were used in this study. A PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days. After model induction, mice in the intervention group received TMAS once daily for 14 consecutive days, whereas the corresponding control group received sham stimulation. The stimulation target was positioned over the primary motor cortex (M1). Motor performance was evaluated using the pole test and the open-field test. To verify the activation effect of TMAS on the target cortical region, c-Fos immunohistochemistry was performed in the M1. To assess nigral dopaminergic neuronal injury, tyrosine hydroxylase (TH) immunohistochemistry was used to quantify TH-positive neurons in the SNc. Mitochondrial function was evaluated by measuring reactive oxygen species (ROS) levels and adenosine triphosphate (ATP) content in the SNc. Western blot was further performed to determine the expression of mitophagy-related proteins, including PINK1, Parkin, LC3-II, and p62, as well as mitochondrial dynamics-related proteins, including Drp1 and Opa1. ResultsTMAS significantly increased the number of c-Fos-positive cells in M1 (P<0.000 1), indicating effective activation of neurons in the targeted cortical region. Compared with the control group, MPTP-treated mice exhibited marked motor dysfunction, including a significant reduction in total distance traveled in the open-field test (P<0.000 1) and mean speed (P=0.000 1), as well as significant prolongation of turn time and total climbing time in the pole test (P<0.000 1). These behavioral impairments were accompanied by a substantial loss of TH-positive dopaminergic neurons in the SNc, whereas TMAS significantly increased TH-positive neuron survival (P<0.000 1). In parallel, MPTP induced a pronounced increase in ROS levels and a significant reduction in ATP content, indicating severe mitochondrial dysfunction and energy metabolism impairment (P<0.01). TMAS treatment significantly improved motor performance, as reflected by the reversal of MPTP-induced impairment in the open-field and pole tests, and significantly reduced ROS accumulation (P<0.01) while restoring ATP production (P<0.001). At the molecular level, MPTP markedly downregulated PINK1 and Parkin, decreased p62 expression, increased LC3-II accumulation, elevated Drp1 expression, and reduced Opa1 expression, whereas TMAS significantly reversed these abnormalities, suggesting restoration of mitophagy-related mitochondrial quality control and re-establishment of mitochondrial fission-fusion balance. Collectively, these findings indicate that TMAS ameliorates MPTP-induced neurotoxicity and restores mitochondrial homeostasis and energy metabolism. ConclusionTMAS effectively attenuates neural damage and improves motor dysfunction in MPTP-induced PD mice. Its neuroprotective effects are closely associated with multidimensional regulation of the mitochondrial quality control system, including restoration of PINK1/Parkin-mediated mitophagy and rebalancing of Drp1/Opa1-related mitochondrial dynamics. Rather than acting only as a symptomatic neuromodulatory intervention, TMAS may influence a key pathological axis of PD by improving mitochondrial homeostasis in SNc and protecting nigral dopaminergic neurons. These findings provide experimental evidence supporting TMAS as a promising non-invasive physical intervention for PD.