BackgroundGreenness exposure is beneficial to human health, but its potential mechanisms through which the risk for metabolic syndrome (MetS) could be reduced have been poorly studied. We aimed to estimate the greenness-MetS association in southeast China and investigate the independent and joint mediation effects of physical activity (PA), body mass index (BMI), and air pollutants on the association.MethodsA cross-sectional study was conducted among the 38,288 adults based on the Fujian Behavior and Disease Surveillance (FBDS), established in 2018. MetS was defined as the presence of three or more of the five components: abdominal obesity, elevated triglyceride, reduced high-density lipoprotein cholesterol (HDL-C), high blood pressure, and elevated fasting glucose. The residential greenness exposure was measured as the 3-year mean values of the normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI) within the 250, 500, and 1,000 meters (m) buffer zones around the residential address of each participant. Logistic regression models were used to estimate the greenness-MetS association. The causal mediation analysis was used to estimate the independent and joint mediation effects of PA, BMI, particulate matter with an aerodynamic diameter of 2.5 μm (PM2.5), particulate matter with an aerodynamic diameter ≤ 10 μm (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2).ResultsEach interquartile range (IQR) increase in greenness was associated with a decrease of 13% (OR = 0.87 [95%CI: 0.83, 0.92] for NDVI500m and OR = 0.87 [95%CI: 0.82, 0.91] for EVI500m) in MetS risk after adjusting for covariates. This association was stronger in those aged < 60 years (e.g., OR = 0.86 [95%CI: 0.81, 0.92] for NDVI500m), males (e.g., OR = 0.73 [95%CI: 0.67, 0.80] for NDVI500m), having an educational level of primary school or above (OR = 0.81 [95%CI: 0.74, 0.89] for NDVI500m), married/cohabitation (OR = 0.86 [95%CI: 0.81, 0.91] for NDVI500m), businessman (OR = 0.82 [95%CI: 0.68, 0.99] for NDVI500m), other laborers (OR = 0.77 [95%CI: 0.68, 0.88] for NDVI500m), and non-smokers (OR = 0.77 [95%CI: 0.70, 0.85] for NDVI500m). The joint effect of all six mediators mediated about 48.1% and 44.6% of the total effect of NDVI500m and EVI500m on the MetS risk, respectively. Among them, BMI showed the strongest independent mediation effect (25.0% for NDVI500m), followed by NO2 and PM10.ConclusionExposure to residential greenness was associated with a decreased risk for MetS. PA, BMI, and the four air pollutants jointly interpreted nearly half of the mediation effects on the greenness-MetS association.
Objectives: Circadian system is an essential physiological regulator of mammals, and circadian dissonance may be associated with the risk of metabolic disorders. However, evidence regarding its role in the development of metabolic-associated fatty liver disease (MAFLD) is scarce, particularly in employed adults. Methods: We conducted a longitudinal study of 1,309 employed adults in Southwestern China with a five-year follow-up from 2017 to 2021. MAFLD was assessed by the presence of hepatic steatosis using abdominal ultrasonography,overweight/obese status, diabetes mellitus, metabolic dysregulation, or elevation of high-sensitivity C-reactive protein. Circadian dissonance was assessed by the sleep chronotype questionnaire. The logistic random effects model was applied to analyze the 5-year panel data to estimate the association between circadian dissonance and MAFLD, and the potential effect modification of demographics on such association. Results: The MAFLD prevalence of participants was 38.7% at baseline and showed an increasing trend during follow-up (p for trends <0.001). We observed that severe circadian dissonance was positively associated with MAFLD (OR: 1.75, 95% CI: 1.09, 2.81). Participants who were minority had a higher risk of developing MAFLD (OR: 2.83, 95% CI: 1.09, 7.33), and those who had an undergraduate education or above had a lower risk (OR: 0.60, 95% CI: 0.40, 0.90). Participants’ follow-up year (OR: 1.81, 95% CI: 1.70, 1.94), higher level of AST (OR: 1.01, 95% CI: 1.01, 1.02),and higher level of ALT (OR: 1.03, 95% CI: 1.02, 1.03) were positively associated with the risk of MAFLD. Conclusions: Severe circadian dissonance may increase the odds of MAFLD in employed adults. Improving circadian rhythms could reduce the risk of MAFLD and increase life expectancy among employed adults.
Background: Non-mutational mechanisms were recently discovered leading to reversible drug tolerance. Despite the rapid elimination of majority tumor cells, a small sub-population of ‘‘drug-tolerant’’ cells remain viable with lethal drug exposure, which may further lead to resistance or tumor relapse. Several signaling pathways are involved in the local or systemic inflammatory responses contributing to drug-induced phenotypic switch.Results: In this study, we report Toll like receptor 4 (TLR4)-interacting lipid docosahexaenoic acid (DHA) restores the cytotoxic effect of doxorubicin (DOX) in the lipopolysaccharide-treated breast tumor cell line 4T1, preventing the phenotypic switch to drug-tolerant cells, which significantly reduces primary tumor growth and lung metastasis in both 4T1 orthotopic and experimental metastasis models. Importantly, DHA in combination with DOX delays and inhibits tumor recurrence following surgical removal of the primary tumor. Furthermore, coencapsulation of DHA and DOX in a nanoemulsion significantly prolongs the survival of mice in the postsurgical 4T1 tumor relapse model with significantly reduced systemic toxicity. Conclusions: The synergistic antitumor, anti-metastasis and anti-recurrence effects of DHA plus DOX combination is likely mediated by attenuating TLR4 activation thus sensitizing tumor cells to standard chemotherapy.
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