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.

Aim To explore the therapeutic effects of resveratrol(Res)on hepatic inflammation and oxida-tive stress in rheumatoid arthritis(RA),and to eluci-date the relationship of the regulatory mechanism of the Nrf2/Keap1 signaling pathway in it.Methods A mouse model of arthritis was induced using chicken type Ⅱ collagen in combination with complete Freund's adjuvant,and Res was administered by tube feeding for treatment.Serum liver function indices and levels of hepatic inflammation and oxidative stress were detected in mice.An in vitro cellular model of hepatic inflam-mation and oxidative stress was established by treating mouse primary hepatocytes(MPHs)with TNF-α(5μg·L-1),cell proliferation inhibition was detected by CCK-8,and inflammation and oxidative stress-relat-ed indices were detected by protein blotting.The in-trinsic mechanisms by which Res attenuated hepatic in-flammation and oxidative stress in rheumatoid arthritis were explored by treating MPHs with Nrf2 inhibitor and Keap1 overexpression plasmid.Results Res signifi-cantly reduced the levels of inflammation and oxidative stress in hepatic tissues of collagen-induced arthritis mice as well as TNF-α-treated MPHs,and activated the Nrf2/Keap1 signaling pathway.Inflammation and oxidative stress levels in MPHs were exacerbated by the use of Nrf2 inhibitors and Keap1 overexpression,which promoted apoptosis.Conclusion Res attenuates he-patic inflammation and oxidative stress in rheumatoid arthritis via the Nrf2/Keap1 pathway.

Objective:To analyze the dynamic changes of serum exosome miR-552 and miR-653 levels in pa-tients with gastric cancer before and after chemotherapy and their relationship with clinical benefit.Methods:IA total of 128 patients with gastric cancer received chemotherapy from January 2022 to January 2024.According to the chemo-therapy effect,the two groups were divided into disease progression group and disease remission group.The levels of serum exosome miR-552 and miR-653 before and after chemotherapy were detected in the two groups,the risk fac-tors affecting the chemotherapy effect of gastric cancer patients were screened,the risk nomogram model was con-structed,and the efficacy was evaluated.Results:The proportion of TNM stage(Ⅲ+Ⅳ),lymph node metastasis,dis-tant metastasis,tumor size(>5 cm),invasion depth(T3/T4)and tumor growth pattern(invasive type)in disease progres-sion group was higher than that in disease remission group(P<0.05).The levels of serum exosomes miR-552 and miR-653 in disease progression group were higher than those in remission group before and after chemotherapy(P<0.05).Compared with before chemotherapy,miR-552 and miR-653 levels in both groups decreased(P<0.05).Logistic regres-sion analysis showed that TNM stage,lymph node metastasis,distant metastasis,tumor size,invasion depth,miR-552 and miR-653 were all risk factors affecting the chemotherapy efficacy of gastric cancer(P<0.05).ROC curve results showed that the AUC,95%CI,sensitivity and specificity of risk nomogram model to predict chemotherapy efficacy of gastric cancer were 0.867,0.672～0.991,92.80%and 80.40%,respectively(P<0.001).Calibration curve results showed that both predicted and actual predicted values were near the ideal curve,and the Hosmer-Lemeshow goodness of fit curve test χ2=1.869,P=0.782.Conclusion:The levels of serum exosomes miR-552 and miR-653 are closely related to the chemotherapy efficacy of gastric cancer,and dynamic monitoring of the above indexes is helpful for the evaluation of the disease and prognosis of gastric cancer.In this study,the risk nomogram model constructed based on the above indexes and other risk factors has high predictive value and clinical practicability for chemotherapy efficacy in patients with gastric cancer.

Aim To investigate the protective effects of Tilianin on lipopolysaccharide(LPS)-induced septice-mia-induced myocardial injury in rats and to explore the related mechanisms.Methods Animals were ran-domly grouped and a rat septicemia-induced myocardial injury model was constructed.Echocardiography was used to assess the cardiac function of rats,left ventricu-lar internal diameter at end-diastole(LVIDd)and left ventricular internal diameter at end-systole(LVIDs)were measured,and left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)were calculated;the kits were used to detect the serum activity of the relevant cardiac enzymes and the level of inflammatory factors;HE staining was used to observe the morphological changes of myocardium;immunofluorescence staining of cardiac tissues was used to detect the nuclear translocation of NF-κB p65;Western blot was used to detect the expression of TLR4,MyD88,p-NF-κB p65,and NLRP3 proteins in cardiac tissues.Results Compared with the model group,each administration group differently upregulated LVEF,LVFS,and LVIDs,and improved the coordina-tion of LV wall fluctuations in the model group of rats;cardiac enzymes LDH and CK-MB levels increased,and levels of inflammatory factors TNF-α,IL-6,and IL-1 β were reduced,exerting cardioprotective effects;HE staining showed that myocardial tissue cell gap was re-duced,myocardial fiber breakage was reduced,cardio-myocyte arrangement tended to be normal,and inflam-matory cell infiltration was reduced;NF-κB p65 entry into the nucleus was reduced,and phosphorylated NF-κB p65(p-NF-κB p65)expression was reduced;and Western blot results showed that the expression of TLR4,MyD88,and NLRP3 proteins was reduced.Conclusions Tilianin pretreatment reduces serum my-ocardial enzymes and inflammatory factors and im-proves myocardial injury in rats with septicemia-in-duced myocardial injury,which may be related to the Tilianin anti-TLR4/NF-κB/NLRP3 inflammatory signa-ling pathway.

40 patients with choronic periodontitis underwent periodontal basic treatment were randomly divided into 2 groups(n=20).The patients in control group used special toothpaste and toothbrush to brush their teeth after meals,those in the experimental group brushed their teeth with special toothpaste and toothbrush in the morning,evening and after meals,and wore personalized film pressing trays containing cymene care solution while sleeping at night.Gingival bleeding,periodontal pocket depth and attachment loss were ob-served after 4,6 and 10 weeks respectively.The personalized tray combined with cymbidium reduced the depth of periodontal pocket(P＜0.05)and the rate of probing bleeding sites(P＜0.05)more effectively,and showed no statistical significance in the change of attachment loss(P＜0.05).Cymene care solution is effective in the improvement of periodontal health.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Objective To analyze the effects of tyrosinase on choroidal and retinal thickness and blood flow changes in guinea pigs,and to explore the role of tyrosinase in the development and progression of myopia.Methods A total of 30 three-week-old male tri-colored guinea pigs and 10 albino guinea pigs were selected and divided into four groups:control group(tri-colored hyperopic guinea pigs,with no intervention),albino group(albino myopic guinea pigs,with no inter-vention),myopia group(tri-colored myopic guinea pigs,with no intervention),and injection group[tri-colored hyperopic guinea pigs,injected with tyrosinase inhibitor(6 250 μg·L-1),100 μL per day].The experiment lasted for 4 weeks.The refractive status and axial length(AL)of the guinea pigs in each group were measured,along with ocular biometric param-eters related to axial length[anterior chamber depth,aqueous humor depth(AQD),central corneal thickness,lens diame-ter,vitreous chamber depth(VCD)].Optical coherence tomography was used to measure the retinal thickness,choroidal thickness(ChT),and choroidal blood perfusion(ChBP)in different regions of the guinea pigs.The tyrosinase activity in the vitreous and retina of guinea pigs in each group was measured.The expression levels of neurotransmitters in the vitre-ous and retina of guinea pigs in each group were detected.Results The differences in refractive status between the albi-no group and the control group at 0,2,and 4 weeks of the experiment were statistically significant(F=8.972,P＜0.05).At the 4th week of the experiment,the refractive status of the injection group was lower than that of the control group,and the AL was greater than that of the control group,with statistically significant differences(both P＜0.05).Further analysis of AL-related biometric parameters revealed that only AQD and VCD were associated with the changes in AL of guinea pigs in each group.At the 0th week of the experiment,the average retinal thickness of the control group was greater than that of the albino group,with a statistically significant difference(t=-9.007,P＜0.000 1).Moreover,the differences in reti-nal thickness in the outer retina across different directions and time points were statistically significant(all P＜0.05).The differences in retinal thickness between the control and albino groups were mainly concentrated in the outer retina.The ChT of the albino group was less than that of the control group,with a significant difference between groups(F=4.809,P=0.030).The ChBP of the control group was significantly higher than that of the albino group at 0,2,and 4 weeks of the experiment(all P＜0.05).At the 4th week of the experiment,the tyrosinase activity in the vitreous of the injection,albi-no,and myopia groups was lower than that of the control group,with statistically significant differences(all P＜0.05).The differences in neurotransmitters between the albino and control groups were mainly concentrated in the vitreous.In the retina,the ornithine level in the myopia group was higher than that in the albino and control groups,and the tryptophan levels in the myopia and control groups were higher than that in the albino group,with statistically significant differences(all P＜0.05).Conclusion Tyrosinase plays a crucial role in the development of myopia,regulating the development of refractive status by influencing the physiological properties of the retina and choroid.

Aim To investigate the effects of hydroxyl-safflor yellow A(HSYA)on the regenerative and re-pair functions of human umbilical cord mesenchymal stem cells(hUC-MSCs).Methods hUC-MSCs were mechanically isolated,and their morphology was ob-served.Cell surface marker expression was analyzed u-sing flow cytometry.Osteogenic differentiation was used to confirm the multipotency of the cells.The cells were treated with various concentrations of HSYA(0,100,200,400,600 μmol·L-1),and the optimal con-centration and duration of treatment were determined u-sing the CCK-8 assay.Cells were divided into four groups:control,100,200,and 400 μmol·L-1.The proliferative capacity of hUC-MSCs was assessed by EdU incorporation.Vascular endothelial growth factor(VEGF)and brain-derived neurotrophic factor(BD-NF)levels in the culture supernatant were measured u-sing enzyme-linked immunosorbent assays.Cell migra-tion ability was evaluated by Scratch assays.The ex-pression levels of VEGF,BDNF,and fibroblast growth factor 2(FGF2)were detected by Western blotting.Results The isolated cells exhibited characteristics consistent with stem cell surface markers and demon-strated osteogenic and adipogenic differentiation poten-tial.After 48 hours of treatment,no cytotoxicity was observed at concentrations of 100,200,and 400 μmol·L-1compared to the control group.HSYA signifi-cantly increased the number of EdU-positive cells and cell migration rate,with the most pronounced effect was achieved at 200 μmol·L-1(P＜0.01).VEGF and BDNF levels in the supernatant were elevated,with the highest expression observed at 200 μmol·L-1(P＜0.01).Similarly,the expression levels of BDNF,VEGF,and FGF2 were significantly upregulated in the HSYA groups,with the highest levels at 200 μmol·L-1(P＜0.01).Conclusion HSYA promotes the proliferation,migration and angiogenesis of hUC-MSCs,with an optimal concentration of 200 μmol·L-1.