Objective:To explore the impact of the stimulator of interferon genes(STING)-interferon regulatory factor 3(IRF3)pathway on the senescence of rapid pacing HL-1 myocytes.Methods:HL-1 cells were divided into five groups: the control group(HL-1 cells without any treatment), pacing group(HL-1 cells paced for 48 hours), STING siRNA group(HL-1 cells paced for 48 hours and transfected with STING siRNA), NC siRNA group(HL-1 cells paced for 48 hours and transfected with NC siRNA), and H151 inhibitor group(HL-1 cells paced for 48 hours with the addition of 1 μmol/L STING inhibitor H151). Mitochondrial membrane potential was assessed in control and pacing group cells, and mitochondrial MitoTracker and TFAM co-localization staining was performed on these cells.Cellular senescence was evaluated using β-galactosidase staining in each group, and the positive rate of cellular senescence was observed and calculated.Western blotting was employed to detect the expression levels of STING, IRF3, P-IRF3, P16, P21, and P53 proteins in all groups.Immunofluorescence was utilized to examine the expression distribution of STING and P21 across the various groups.ELISA was performed to measure the concentrations of interleukin(IL)-1β, IL-6, and IL-8 in the cell supernatants from each group as part of the senescence-associated secretory phenotype(SASP).Results:Compared with the control group, the ratio of mitochondrial JC-1 multimer to monomer was significantly decreased in the pacing group( t=16.42, P<0.05), the co-localization of mitochondrial MitoTracker and TFAM in the cells was significantly weakened, the proportion of cells with positive cellular senescence-associated β-galactosidase staining significantly increased in the pacing group, the expression levels of STING, P-IRF3/IRF3, P16, P21, and P53 proteins were significantly elevated in the pacing group, and the concentrations of IL-1β, IL-6, and IL-8 in the cell supernatants were markedly increased.Compared with the pacing group, the proportion of cells with positive cellular senescence-associated β-galactosidase staining decreased in the STING siRNA group and H151 inhibitor group ( F= 18.13, P<0.05), the expression levels of STING, P-IRF3/IRF3, P16, P21, and P53 were reduced in the STING siRNA group and H151 inhibitor group ( F=16.84, 26.56, 74.70, 31.80, 31.23, all P<0.05), and the concentrations of IL-1β, IL-6, and IL-8 in the cell supernatants decreased( F=197.80、1 339.00、1 308.00, all P<0.001). Conclusions:Rapid pacing of HL-1 cells can promote mtDNA release into the cytoplasm, activate the STING-IRF3 pathway, accelerate cellular senescence, and enhance the secretion of SASP.Inhibiting the expression of STING can delay the senescence induced by the rapid pacing of HL-1 cells and reduce SASP secretion.

Objective:To explore the impact of the stimulator of interferon genes(STING)-interferon regulatory factor 3(IRF3)pathway on the senescence of rapid pacing HL-1 myocytes.Methods:HL-1 cells were divided into five groups: the control group(HL-1 cells without any treatment), pacing group(HL-1 cells paced for 48 hours), STING siRNA group(HL-1 cells paced for 48 hours and transfected with STING siRNA), NC siRNA group(HL-1 cells paced for 48 hours and transfected with NC siRNA), and H151 inhibitor group(HL-1 cells paced for 48 hours with the addition of 1 μmol/L STING inhibitor H151). Mitochondrial membrane potential was assessed in control and pacing group cells, and mitochondrial MitoTracker and TFAM co-localization staining was performed on these cells.Cellular senescence was evaluated using β-galactosidase staining in each group, and the positive rate of cellular senescence was observed and calculated.Western blotting was employed to detect the expression levels of STING, IRF3, P-IRF3, P16, P21, and P53 proteins in all groups.Immunofluorescence was utilized to examine the expression distribution of STING and P21 across the various groups.ELISA was performed to measure the concentrations of interleukin(IL)-1β, IL-6, and IL-8 in the cell supernatants from each group as part of the senescence-associated secretory phenotype(SASP).Results:Compared with the control group, the ratio of mitochondrial JC-1 multimer to monomer was significantly decreased in the pacing group( t=16.42, P<0.05), the co-localization of mitochondrial MitoTracker and TFAM in the cells was significantly weakened, the proportion of cells with positive cellular senescence-associated β-galactosidase staining significantly increased in the pacing group, the expression levels of STING, P-IRF3/IRF3, P16, P21, and P53 proteins were significantly elevated in the pacing group, and the concentrations of IL-1β, IL-6, and IL-8 in the cell supernatants were markedly increased.Compared with the pacing group, the proportion of cells with positive cellular senescence-associated β-galactosidase staining decreased in the STING siRNA group and H151 inhibitor group ( F= 18.13, P<0.05), the expression levels of STING, P-IRF3/IRF3, P16, P21, and P53 were reduced in the STING siRNA group and H151 inhibitor group ( F=16.84, 26.56, 74.70, 31.80, 31.23, all P<0.05), and the concentrations of IL-1β, IL-6, and IL-8 in the cell supernatants decreased( F=197.80、1 339.00、1 308.00, all P<0.001). Conclusions:Rapid pacing of HL-1 cells can promote mtDNA release into the cytoplasm, activate the STING-IRF3 pathway, accelerate cellular senescence, and enhance the secretion of SASP.Inhibiting the expression of STING can delay the senescence induced by the rapid pacing of HL-1 cells and reduce SASP secretion.

Objective:To investigate the effects of tetrabromobisphenol A (TBBPA) on ionizing radiation (IR)-induced liver toxicity based on a zebrafish model and provide a scientific basis for assessing microplastic-radiation exposure hazards to the survival and health of aquatic organisms and humans.Methods:Healthy adult zebrafish aged 4-6 months were grouped (20 fish each group, sex in half) by random number table method in three different ways. The TBBPA exposure concentration screening experiment was divided into 4 groups: control group and TBBPA (3, 30 and 300 μg/L) treatment groups. The experiment of effects of double exposure on liver function was divided into 5 groups: control group, IR (10, 20 or 30 Gy) groups and IR+ TBBPA (60, 300 and 1 500 μg/L) treatment groups. The experiment of effects of TBBPA on hepatic radiation toxicity was divided into 3 groups: control group, IR (20 Gy) group, and IR+ TBBPA (300 μg/L) group. The changes in liver function indexes, oxidative stress markers, pro-inflammatory cytokines, and liver cell apoptosis were monitored, differential metabolic pathways and metabolites were identified upon untargeted metabolomics assays, and inter-group data were compared by One-way ANOVA test.Results:The activities of ALT and AST in zebrafish liver increased in a dose-dependent manner after exposure to TBBPA, and the differences between 300 μg/L TBBPA group and control group were statistically significant ( t=-2.22, -3.20, P<0.05). IR at a dose of 20 Gy or above induced a significant decline of liver function, and at this radiation dose, combined exposure to 300 μg/L or above TBBPA intensified the liver toxicity (compared with the control group, t=-8.18 to -4.63, P<0.05, compared with IR group, t=-5.22 to -0.30, P < 0.05). Compared with the control group, the activities of ALT and AST, levels of ROS, MDA and SOD, mRNA and protein expression levels of TNF-α, IL-1β, Cox-2, Caspase-8 and Caspase-9, and cell apoptosis in zebrafish livers of IR and IR+ TBBPA groups increased gradually (compared with the control group, t=-12.29 to -2.88, P<0.05, compared with IR group, t=-4.40 to -2.31, P<0.05). The differences in the content of D-gluconic acid, p-cresol and other metabolites in liver tissues were more and more significant among the three groups, involving multiple KEGG pathways such as biosynthesis, degradation and metabolism. Conclusions:Exposure to 300 μg/L TBBPA can aggravate IR-induced liver toxicity of zebrafish, which involves the mechanism that further elevates the levels of oxidative stress, inflammation, and apoptosis, as well as radiation-induced liver metabolic disorders.

Objective: To analyze the hearing self-protection behavior patterns and internal factors of workers exposured to occupational noise in an aircraft manufacturing industry based on health belief model, so as to provide reference for further health promotion programs and intervention measures. Methods: A total of 1600 front-line workers were selected from 10 units of an aircraft manufacturing enterprise by cluster sampling method. The basic and occupational information of employees were collected, and a self-reported questionnaire was designed according to the health belief model to acquire the hearing self-protection behaviors of workers. Results: There were significant differences in the perceived severity, perceived benefit, perceived impairment, self-efficacy and behavioral incentive scores of different hearing self-protection behaviors among the noise-causing workers (P<0.05). There were significant differences in the distribution of hearing self-protection behaviors among different genders, ages, education levels, length of service, initial noise exposure time and cumulative noise reception time (P<0.05). The perceived benefits, perceived barriers, behavioral incentives, self-efficacy scores, and educational attainment of the noise-causing workers were all related to the type of hearing self-protection behavior (P<0.05) . Conclusion The educational level and health belief model can predict the hearing self-protection behavior patterns of front-line workers to some extent, more attention should be paid to the monitoring of the well-educated employees.

Background and purpose: Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) can be used for magnetic resonance imaging systemic examination, especially in examing the metastatic lesions, lymph node and bone diseases, and the imaging result is similar with PET. This study aimed to evaluate the application value of magnetic resonance DWIBS and positron emission tomography with computed tomography (PET/CT) on malignant metastatic diseases. Methods: Thirty-six patients confirmed with malignant tumors accompanying metastasis by the pathology of operation or biopsy underwent both DWIBS imaging and PET/CT, chi-square test and Kappa test were used for comparing the detection results of metastasis by these 2 imaging methods. Results:Among the 36 malignant tumor patients with 238 metastatic lesions, 218 (91.6%, 218/238) lesions in DWIBS and 209 (87.8%, 209/238) lesions in PET/CT were detected, with 200 lesions detected by the two methods simultaneously, and the concordance rate was 88.7%(211/238);but there was no statistical signiifcance between this two methods (χ2=1.843, P=0.157). Kappa test showed a fair concordance rate between DWIBS and PET/CT (P=0.000).There were different significance between DWIBS and PET/CT in detecting metastatic lesions of brain and bone (P=0.005 and 0.031);But there was no signiifcant differences (P=0.309 and 1.000) in detecting metastatic lesions of lymph nodes and liver. Conclusion:DWIBS could detect metastatic lesions effectively, and there is ifne consistency with PET/CT. DWIBS is more sensitive than PET/CT in detecting metastatic lesions of brain and bone, so DWIBS could be chosed for screening metastatic lesions according to the characteristics of different primary tumors.