Objective To elucidate the molecular mechanism of sirtuin-3 (SIRT3) in regulating mitochondrial biogenesis in human renal tubular epithelial cells. Methods Cells were stimulated with different concentrations of H₂O₂ and divided into four groups: control (NC), 50 μmol/L H₂O₂, 110 μmol/L H₂O₂ and 150 μmol/L H₂O₂. SIRT3 protein expression was then measured. SIRT3 was knocked down with siRNA, and cells were further assigned to five groups: control (NC), negative-control siRNA (NCsi), SIRT3-siRNA (siSIRT3), NCsi+H₂O₂, and siSIRT3+H₂O₂. After 24 h, cellular adenosine triphosphate (ATP) and mitochondrial superoxide anion (O₂•⁻) levels were determined, together with mitochondrial expression of SIRT3, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), superoxide dismutase 2 (SOD2), acetylated-SOD2 and adenosine monophosphate activated protein kinase α1 (AMPKα1). Results The 110 and 150 μmol/L H₂O₂ decreased SIRT3 protein (both P<0.05). ATP and mitochondrial O₂•⁻ did not differ between NC and NCsi groups (both P>0.05). Compared to the NCsi group, the siSIRT3 group exhibited elevated O₂•⁻ level, decreased SIRT3 protein and increased expression levels of SOD2 and acetylated SOD2 protein (all P<0.05). Compared to the NCsi group, the NCsi+H₂O₂ group exhibited decreased cellular ATP levels, elevated mitochondrial O₂•⁻ levels, and reduced protein expression levels of SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 (all P<0.05). Compared with the siSIRT3 group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 protein expression levels and a decrease in acetylated SOD2 protein expression levels (all P<0.05). Compared with the NCsi+H₂O₂ group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, AMPKα1, PGC-1α and NRF1, TFAM protein expression levels, and an increase in SOD2 and acetylated SOD2 protein expression levels (all P<0.05). Conclusions SIRT3 promotes mitochondrial biogenesis in tubular epithelial cells via the AMPK/PGC-1α/NRF1/TFAM axis, representing a key mechanism through which SIRT3 ameliorates oxidative stress-induced mitochondrial dysfunction.

Background As one of the key populations in the prevention and treatment of iodine deficiency disorders, it is important to continuously monitor the iodine nutritional level of school-age children. The current reference interval for thyroid volume in China is based on age only, without taking into account differences in individual developmental levels, and the distribution of thyroid volume may vary regionally due to economic, demographic, and environmental factors. The current reference cut-off points for thyroid volume proposed by the World Health Organization are not based on the Chinese population. Objective To understand the iodine nutritional status and distribution of thyroid volume (Tvol) among children aged 8-10 years in Huangpu District, Shanghai, China, to identify impact factors of Tvol, and to propose a reference range upper limit for local thyroid health surveillance, so as to provide a basis for goiter control and prevention. Methods Six hundred children aged 8-10 years in Huangpu District were recruited in 2017, 2020, and 2023, and body height, weight, thyroid volume, urinary iodine, and iodine content of household edible salt were determined. A multilevel model was constructed using population density and area as regional variables, and age, body surface area (BSA), and body mass index (BMI) as potential impact factors for at the individual level, to assess their effects on thyroid volume. Quantile regression of thyroid volume was performed, and the 98th percentile (P₉₈) of thyroid volume was predicted based on age and BSA. Results The iodized salt coverage in the households of surveyed children in 2017, 2020, and 2023 was 72.0%, 57.0%, and 48.0%, respectively, and the iodized salt coverage decreased by year (χ²=24.31, P<0.001). The urinary iodine level of children in 2017 was higher than that in 2020 and 2023 (χ²=18.77, P<0.001). The Tvol medians of children in 2017, 2020, and 2023 were 2.29, 2.49, and 2.97 mL, respectively, and the Tvol increased by year (χ²=60.04, P<0.001). The proportion of goiter was higher in children in 2023 than in 2017 and 2020 (χ²=6.57, P<0.05). Sex differences were not statistically significant for urinary iodine levels, thyroid volume, and goiter. The median Tvol was 2.26, 2.58, and 2.76 mL in children of 8, 9, and 10 years old respectively, and the Tvol increased with age (χ²=49.02, P <0.001). Tvol was positively correlated with age, BSA, and BMI with correlation coefficients of 0.2846, 0.3723, and 0.2950, respectively. The final quantile regression model showed that the strongest effect of BSA was associated with the 98th percentile of Tvol. Multilevel models considering population density or area as regional variables failed to achieve convergence. Conclusion To establish the upper limit of the reference interval for thyroid volume of healthy children in Huangpu District, the effects of age and BSA should be considered at the individual level, and the upper limit of the normal interval for goiter screening is suggested to be the 98th percentile value of BSA at the same age. In addition, the adaptability of population density and regional area as indicators of regional aggregation of thyroid volume distribution still needs to be further explored.

Digital polymerase chain reaction(dPCR)enables absolute quantitative detection of nucleic acid samples.Since the quantitative upper and lower limits of detectable samples mainly depend on the volume and number of single droplets,the abundance of the sample to be tested,the volume of single droplets,and the number of droplets need to be adapted.For samples with unknown abundance,repeated adjustment of droplet size is not allowed.In this study,a one-step double-volume droplet generation method was proposed,and a double-volume droplet microfluidic chip was developed to verify the quantitative detection capability of the chip using a duck-derived kit.The results showed that the droplets with different volumes had different quantitative capabilities.Large-volume droplets had higher reliability for low-abundance sample concentrations,while small-volume droplets had advantages in detecting high-abundance sample concentrations.The double-volume droplets produced by the double-volume droplet microfluidic chip proposed in this study greatly improved the reliability of quantitative capabilities,and had broad application prospects in detection of precious nucleic acid samples with unknown abundance in the field of microfluidic PCR.

Decabromodiphenyl ether(BDE-209)and decabromodiphenyl ethane(DBDPE)are widely used brominated flame retardants,which have been detected in the atmosphere,water,soil,and various organisms.In this study,a method based on high-performance liquid chromatography-inductively coupled plasma-mass spectrometry(HPLC-ICP-MS)was developed for determination of BDE-209 and DBDPE in sediment.Firstly,the target compounds in the sediments were extracted by accelerated solvent extraction(ASE),and the extraction solvent was hexane/dichloromethane(1∶1,V/V).The extract was concentrated by rotary evaporation and purified by a composite silica gel column(6 g neutral silica gel,8 g acidic silica gel,and 4 g anhydrous sodium sulfate),concentrated by nitrogen blowing,and then re-dissolved with 1 mL of toluene for instrumental determination.The chromatographic separation was carried out on a TC-C18(2)column(250 mm×4.6 mm)with isocratic elution using methanol-isopropanol-water(89∶6∶5,V/V)as the mobile phase,and the samples were separated within 20 min.Further,the Br element was quantified by ICP-MS to realize the detection of the target.The results showed that the method established in this study exhibited good linearity(R2>0.999)in the range of 100-10000 ng/mL,and the limits of quantification(LOQs)of the method were 2.0 ng/g for BDE-209 and 10.0 ng/g for DBDPE,with the relative standard deviations(RSDs,n=3)lower than 10%,and the recoveries were in the acceptable range(80.9%-120.7%).The matrix effect was effectively controlled within 10%.In addition,by analyzing the actual sediment samples from Guangxi,a background point,and Taizhou,Zhejiang,a typical contaminated area,it was found that neither BDE-209 nor DBDPE was detected in the sediment from Guangxi,while the concentrations of BDE-209 and DBDPE in the sediment from Zhejiang ranged from 1591.8 to 3362.9 ng/g,which further demonstrated the applicability and reliability of the method for analyzing actual environmental samples.This study provided a strong technical support for the accurate detection of POPs in the environment.

Objective:To investigate the role and possible mechanism of tripartite motif-containing protein 72 (Trim72) in acute viral myocarditis (AVMC) in mice.Methods:A mouse model of AVMC was established by intraperitoneal injection of Coxsackievirus B3 (CVB3, 2.0 × 10 5 PFU/mouse). Forty mice were randomly divided into the negative control (NC) + phosphate-buffered saline (PBS) group (NC+PBS group), Trim72 overexpression + PBS group (Trim72 + PBS group), NC + CVB3 group, and Trim72 + CVB3 group ( n = 10). Fourteen days before modeling, mice in each group were injected with adeno-associated virus type 9 vector (AAV9) encoding either negative control or Trim72 overexpression (5.0 × 10 11 VG/mouse) via tail vein. Subsequently, PBS or CVB3 was injected intraperitoneally in the PBS and CVB3 groups, respectively. After seven days, the surviving mice were euthanized, and the heart and serum samples were collected. HE and TUNEL staining were used to observe the cardiac pathological changes and cardiomyocyte apoptosis, respectively. The mRNA expression levels of Trim72 and pro-inflammatory cytokines TNF-α, IL-6, and IL-1β in myocardial tissues of each group were detected by RT-qPCR. The protein levels of cTnI, TNF-α, IL-6, and IL-1β in serum were detected by ELISA. The expression levels of Trim72, apoptosis-related proteins (Bax, Bcl-2, Cleaved caspase-3, Caspase-3), TLR4, p-p65, and p65 were detected by Western blot. Results:The protein and mRNA expression levels of Trim72 in myocardial tissues of mice in the NC+CVB3 group were significantly downregulated compared with those in the NC + PBS group ( P<0.05). Compared with the NC + CVB3 group, Trim72 overexpression significantly increased the protein and mRNA expression of Trim72 in myocardial tissues ( P<0.05), ameliorated myocardial inflammatory injury, decreased the apoptotic index of cardiomyocytes ( P<0.05), and reduced the levels of pro-inflammation cytokines TNF-α, IL-6, and IL-1β in the myocardium and serum ( P<0.05). Additionally, Trim72 overexpression also downregulated the protein expression of Bax, Cleaved caspase-3/Caspase-3, TLR4, and p-p65, and upregulated the protein expression of Bcl-2 in myocardial tissues ( P<0.05). There was no significant difference in the indexes of mice between the NC + PBS and Trim72 + PBS groups ( P>0.05). Conclusions:Trim72 overexpression attenuates AVMC in mice by inhibiting myocardial inflammatory injury and apoptotic imbalance, and the mechanism may be related to the negative regulation of the TLR4/NF-κB signaling pathway.

Background: Aerobic exercise training and drug therapy are well-established interventions for the prevention and treatment of hypertension and dyslipidemia. We investigated the synergistic effects of aerobic exercise and olmesartan/rosuvastatin on epicardial fat thickness (EFT) and endothelial function in patients with hypertension and dyslipidemia. Methods: A sample of 75 participants with hypertension and dyslipidemia was evaluated for multifactorial cardiovascular risk at baseline and at 6 months of intervention according to anthropometric and hemodynamic components, lipid profile, glycemia, brachial artery flow-mediated dilation (FMD), and EFT. After 3 months of drug therapy only, participants were allocated to one of three conditions: treadmill (n=22), exergame (n=29), or control (n=24). Results: After 12 weeks of drug therapy only, systolic and diastolic blood pressure (3% and 2%, both p<0.05), total cholesterol (6.3%, p<0.01), low-density lipoprotein cholesterol (4.9%, p<0.05), triglycerides (11.1%, p<0.05), fasting blood glucose (10.2%, p<0.01), and glycosylated hemoglobin (3%, p<0.01) were significantly reduced. After 12 weeks of combined aerobic exercise and drug therapy, both the treadmill and exergame groups showed a significant improvement in FMD (both p<0.001) and reduction in EFT (both p<0.001). Systolic and diastolic blood pressures decreased in the treadmill group only (1.9% and 2.7%, respectively, p<0.05). Conclusions Incorporating aerobic exercise into drug therapy regimens can yield synergistic effects, particularly in improving endothelial function and reducing EFT, providing a comprehensive approach to managing cardiovascular risk in patients with hypertension and dyslipidemia.

Alzheimer’s disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory loss. As the incidence of AD continues to rise annually, researchers have shown keen interest in the active components found in natural plants and their neuroprotective effects against AD. Quercetin, a flavonol widely present in fruits and vegetables, has multiple biological effects including anticancer, anti-inflammatory, and antioxidant. Oxidative stress plays a central role in the pathogenesis of AD, and the antioxidant properties of quercetin are essential for its neuroprotective function. Quercetin can modulate multiple signaling pathways related to AD, such as Nrf2-ARE, JNK, p38 MAPK, PON2, PI3K/Akt, and PKC, all of which are closely related to oxidative stress. Furthermore, quercetin is capable of inhibiting the aggregation of β‑amyloid protein (Aβ) and the phosphorylation of tau protein, as well as the activity of β‑secretase 1 and acetylcholinesterase, thus slowing down the progression of the disease.The review also provides insights into the pharmacokinetic properties of quercetin, including its absorption, metabolism, and excretion, as well as its bioavailability challenges and clinical applications. To improve the bioavailability and enhance the targeting of quercetin, the potential of quercetin nanomedicine delivery systems in the treatment of AD is also discussed. In summary, the multifaceted mechanisms of quercetin against AD provide a new perspective for drug development. However, translating these findings into clinical practice requires overcoming current limitations and ongoing research. In this way, its therapeutic potential in the treatment of AD can be fully utilized.

Background: Aerobic exercise training and drug therapy are well-established interventions for the prevention and treatment of hypertension and dyslipidemia. We investigated the synergistic effects of aerobic exercise and olmesartan/rosuvastatin on epicardial fat thickness (EFT) and endothelial function in patients with hypertension and dyslipidemia. Methods: A sample of 75 participants with hypertension and dyslipidemia was evaluated for multifactorial cardiovascular risk at baseline and at 6 months of intervention according to anthropometric and hemodynamic components, lipid profile, glycemia, brachial artery flow-mediated dilation (FMD), and EFT. After 3 months of drug therapy only, participants were allocated to one of three conditions: treadmill (n=22), exergame (n=29), or control (n=24). Results: After 12 weeks of drug therapy only, systolic and diastolic blood pressure (3% and 2%, both p<0.05), total cholesterol (6.3%, p<0.01), low-density lipoprotein cholesterol (4.9%, p<0.05), triglycerides (11.1%, p<0.05), fasting blood glucose (10.2%, p<0.01), and glycosylated hemoglobin (3%, p<0.01) were significantly reduced. After 12 weeks of combined aerobic exercise and drug therapy, both the treadmill and exergame groups showed a significant improvement in FMD (both p<0.001) and reduction in EFT (both p<0.001). Systolic and diastolic blood pressures decreased in the treadmill group only (1.9% and 2.7%, respectively, p<0.05). Conclusions Incorporating aerobic exercise into drug therapy regimens can yield synergistic effects, particularly in improving endothelial function and reducing EFT, providing a comprehensive approach to managing cardiovascular risk in patients with hypertension and dyslipidemia.

Background: Aerobic exercise training and drug therapy are well-established interventions for the prevention and treatment of hypertension and dyslipidemia. We investigated the synergistic effects of aerobic exercise and olmesartan/rosuvastatin on epicardial fat thickness (EFT) and endothelial function in patients with hypertension and dyslipidemia. Methods: A sample of 75 participants with hypertension and dyslipidemia was evaluated for multifactorial cardiovascular risk at baseline and at 6 months of intervention according to anthropometric and hemodynamic components, lipid profile, glycemia, brachial artery flow-mediated dilation (FMD), and EFT. After 3 months of drug therapy only, participants were allocated to one of three conditions: treadmill (n=22), exergame (n=29), or control (n=24). Results: After 12 weeks of drug therapy only, systolic and diastolic blood pressure (3% and 2%, both p<0.05), total cholesterol (6.3%, p<0.01), low-density lipoprotein cholesterol (4.9%, p<0.05), triglycerides (11.1%, p<0.05), fasting blood glucose (10.2%, p<0.01), and glycosylated hemoglobin (3%, p<0.01) were significantly reduced. After 12 weeks of combined aerobic exercise and drug therapy, both the treadmill and exergame groups showed a significant improvement in FMD (both p<0.001) and reduction in EFT (both p<0.001). Systolic and diastolic blood pressures decreased in the treadmill group only (1.9% and 2.7%, respectively, p<0.05). Conclusions Incorporating aerobic exercise into drug therapy regimens can yield synergistic effects, particularly in improving endothelial function and reducing EFT, providing a comprehensive approach to managing cardiovascular risk in patients with hypertension and dyslipidemia.