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.

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.

ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

Objective: To explore the effects of a classroom based transdiagnostic preventive intervention program for emotional disorders on depressive and anxiety symptoms, and resilience among junior high school students, so as to provide reference for promoting adolescent mental health. Methods: From October to December 2023, 72 students from a junior high school in Beijing were recruited as research subjects and divided into an intervention group ( n =36) and a control group ( n =36). The intervention group participated in 8 sessions (40 mins per session) of transdiagnostic prevention intervention course for emotional disorders; the control group students participated in research based learning lessons or class meetings. Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Resilience Scale-8 (RS-8) were used to evaluate junior high school students. The Wilcoxon signed rank test was used to compare the differences in depressive and anxiety symptoms, and resilience scores between the intervention group and the control group before and after the intervention. PROCESS macro was used to test the mediating effect. Results: There were no statistically significant differences in the scores of depressive and anxiety symptoms, and resilience before and after intervention in the intervention group ( Z =-1.07, 0.07, 1.43, all P >0.05). In the control group, the depressive symptoms score was higher after the intervention than before, and the resilience score was lower than before the intervention ( Z = 2.23 , -2.53, both P <0.05). After intervention, the depressive symptoms score in the intervention group was lower than that in the control group, and the resilience score in the intervention group was higher than that in the control group ( Z =-2.09, 3.33, both P < 0.05). The increase in the scores of resilience played a complete mediating role between the intervention and depressive symptoms, with the mediating effect value being -0.98 (95% CI =-2.47 to -0.11), accounting for 30.98% of the total effect. Conclusion Transdiagnostic preventive intervention program for emotional disorders based on classroom could prevent the deterioration of depressive symptom in junior high school students, and maintaining the level of resilience is an important factor for the intervention effect.

Objective: To investigate the epidemiological characteristics of pertussis in Jiaxing City from 2004 to 2023 and spatio-temporal clustering characteristics from 2022 to 2023, so as to provide insights into formulation of pertussis control measures. Methods: Data of pertussis cases in Jiaxing City from 2004 to 2023 were collected through the Infectious Disease Report Information System of Chinese Disease Prevention and Control Information System. The epidemiological characteristics of pertussis cases in Jiaxing City from 2004 to 2023 were descriptively analyzed, and the spatio-temporal clustering characteristics from 2022 to 2023 were analyzed using spatio-temporal scanning. Results: A total of 478 pertussis cases were reported in Jiaxing City from 2004 to 2023, with an average annual reported incidence of 0.53/105. The reported incidence showed an upward trend from 2004 to 2023 (P<0.05), with the highest in 2022 (3.17/105). Higher incidence of pertussis was reported in June to August (149 cases, 31.17%) and November to December (112 cases, 23.43%). There was no statistically significant difference in the reported incidence between males and females (0.56/105 vs. 0.50/105, P>0.05). The cases aged under one year accounted for the highest proportion, with 199 cases (41.63%). Haining City (0.68/105), Jiashan County (0.64/105) and Tongxiang City (0.60/105) ranked the top three in the reported incidence of pertussis. Spatio-temporal scanning analysis showed that from 2022 to 2023, the primary clustering area of pertussis was centered in Daqiao Town of Nanhu District, covering 27 towns (streets) in Nanhu District, Jiashan County, Xiuzhou District and Pinghu City, and the clustering time was from November to December, 2023. Conclusions The reported incidence of pertussis was at a low level in Jiaxing City, but showed an upward trend from 2004 to 2023. The incidence of pertussis was higher among infants under one year of age, peaked in June to August and November to December, and was concentrated in Nanhu District and its surrounding areas.

Post-stroke depression(PSD),a common stroke complication characterized by depressed mood and diminished interest,severely affects patients'recovery and quality of life.Microglial abnormal activation and polarization play key roles in PSD pathogenesis,closely associated with neuroinflammation and imbalance in neu-rotransmitter metabolism.In contrast,traditional Chinese medicine(TCM)demonstrates unique multi-target and multi-level mechanisms:regulating microglial function,ameliorating post-stroke neuroinflammatory environments,and promoting neuroplasticity,thereby potentially alleviating PSD symptoms.This review summarizes TCM's effects on microglial activation/polarization states and its therapeutic advances in PSD,providing novel perspectives and strategies for clinical management.

Aim To explore the mechanism of luteolin in alleviating hepatic fibrosis.Methods C57BL/6 mice were randomly divided into the control group,CCl4 group,silybin group(100 mg·kg-1)and luteo-lin group(100 mg·kg-1).After 10-week modeling and 2-week treatment,the serum levels of aminotrans-ferase and liver histopathology were examined.Hepatic fibrosis and autophagy-related gene expression were as-sessed using immunohistochemistry and immunofluores-cence.Human hepatic stellate cell line(LX2)was cultured and divided into control,TGF-β1(10 mg·L-1),TGF-β1+silybin(40 μmol·L-1),TGF-β1+luteolin(40 μmol·L-1).Fibrotic and autophagy-re-lated markers were analyzed using quantitative real-time PCR,Western blot,immunofluorescence and MDC staining.Results Compared with the CCl4 group,the treatment groups showed significantly improved liver function and reduced hepatic fibrosis,with markedly downregulated COL1A1 and α-SMA expression,and luteolin demonstrated superior efficacy.Compared with TGF-β1 group,luteolin treatment significantly de-creased mRNA levels of COL1A1,ACTA2 and MAP1LC3B,while increasing the mRNA level of SQSTM1,the protein levels of COL1A1 and α-SMA de-creased,p62 was enhanced,the LC3Ⅱ/Ⅰ ratio was downregulated,and autophagy was reduced.These effects of luteolin were reversed by autophagy inducer rapamycin.Conclusion Luteolin alleviates liver fi-brosis by decreasing the autophagy of hepatic stellate cells.

Since 1973,the World Symposium on Pulmonary Hypertension(WSPH)has served as a pivotal platform for the advancing research in pulmonary hypertension(PH).At the 6th WSPH in 2018,the WSPH expert group refined the definitions related to cardiopulmonary physiology and right ventricular(RV)failure,thereby underscoring the critical role of RV dysfunction in the progression of PH.With ongoing advances in the field,RV failure associated with PH has received increasing attention and is now recognized as an important determinant of the prognosis of PH.The 7th WSPH,held in Barcelona,Spain,in 2024,presented the latest perspectives on the RV pathophysiology and its interaction with the pulmonary vasculature.The symposium emphasized new insights into the pathology of RV failure,RV phenotypes across different PH subgroups,and progress in therapeutic approaches targeting RV dysfunction.Additionally,the WSPH expert group delineated prospective research directions and identified unresolved issues.This article will review the RV function-related updates from the 7th WSPH and summarize recent findings,providing a systematic review of the evolution and breakthroughs in RV function research within the context of PH.

Aim To investigate the effect of Huangqi injection(HI)and Huangqi oral solution(HO)on cisplatin-induced nephrotoxicity(CIN)based on un-targeted metabolomics technology and the underlying mechanisms.Methods Sprague Dawley(SD)rats were randomly divided into the blank group,cisplatin(CDDP)model group,HI treatment group,and HO treatment group,then the CIN model was built with low dose multiple intraperitoneal injections of CDDP.Pre-liminary evaluation of the renal protective efficacy of HI and HO was performed by measuring serum creatinine(Scr),blood urea nitrogen(BUN),and organ indi-ces.Further screening and identification of potential biomarkers(PBs)related to CIN and HI/HO pharma-cological effects were attained through metabolomics studies of renal tissues,and pathway enrichment analy-sis was conducted.Results HI and HO significantly restored the abnormal increase in renal function indica-tors and abnormal decrease in organ indices caused by CDDP,as well as significantly improved the abnormal renal metabolic profile induced by CDDP,indicating that both HI and HO had good alleviating effects on CIN.HI significantly reversed 47 out of 54 CIN related PBs,mainly involving metabolic pathways such as glycerophospholipid metabolism,tryptophan metabo-lism,pantothenate and CoA biosynthesis;HO signifi-cantly reversed 18 out of 54 CIN related PBs,mainly involving metabolic pathways such as taurine and hypo-taurine metabolism,ascorbate and aldarate metabo-lism,pentose and glucuronate interconversions.Con-clusions Both HI and HO have significant alleviating effects on CIN.In the short term,HI salleviating effect is superior to that of HO.Overall,the mechanisms by which both alleviate CIN are mainly related to regula-ting lipid metabolism,amino acid metabolism.

Aging is the result of the accumulation of various molecular and cellular damages over time,encompassing 12 characteristic hallmarks divided into three categories.These include primary hallmarks such as genomic instability,telomere attrition,epigenetic alterations,loss of proteostasis,and disabled macroautophagy;antagonistic hallmarks like deregulated nutrient sensing,mitochondrial dysfunction,and cellular senescence;and integrative hallmarks including stem cell exhaustion,altered intercellular com-munication,chronic inflammation and dysbiosis.Therefore,investigating cellular signaling factors within a single pathway is insufficient to comprehensively understand the complex mechanisms underlying aging.Casein kinase Ⅱ(CK2),one of the earliest identified protein kinases,is capable of phosphorylating ser-ine/threonine/tyrosine residues on hundreds of substrates.It exhibits highly constitutive expression and activity,and is extensively involved in the regulation of cellular processes such as proliferation,differenti-ation,apoptosis,stress response,metabolism,and immune function.CK2 plays a unique role in coordi-nating the cross-talk and integration of various signaling pathways,which is crucial for maintaining cell survival and homeostasis.Recent studies have revealed that CK2 exhibits perturbations in both expression levels and enzymatic activity during aging process,with notable heterogeneity observed across different animals,tissues and cellular models.Overall,the downregulation of CK2 expression not only promotes the development of primary hallmarks but also alleviates antagonistic hallmarks and ameliorates integrative hallmarks of aging,demonstrating dual effect and interconnected mechanisms.Notably,aberrant activa-tion in CK2 expression and activity are associated with various aging-related diseases,including cancer,cardiovascular diseases,chronic metabolic disorders,neurodegenerative diseases and skeletal degenera-tive conditions.Therefore,maintaining CK2 homeostasis may represent an effective strategy for delaying aging.This review summarizes the latest advances in CK2 and aging research,providing not only deeper insights into the common mechanisms underlying aging and aging-related diseases,but also a theoretical foundation for identifying potential targets for the early prevention of aging-related diseases.