Eco-friendly synthesis of silver nanoparticles against mosquitoes: Pesticidal impact and indispensable biosafety assessment.

The emergence of nanotechnology has opened new avenues for enhancing pest control strategies through the development of nanopesticides. Green-fabricated nanoparticles, while promising due to their eco-friendly synthesis methods, may still pose risks to biodiversity and ecosystem stability. The potential toxic effects of nanomaterials on ecosystems and human health raise important questions about their real-world application. Understanding the dose-response relationships of nanopesticides, both in terms of pest control efficacy and non-target organism safety, is crucial for ensuring their sustainable use in agricultural settings. This review delves into the complexities of silver nanopesticides, exploring their interactions with arthropod species, modes of action, and underlying mechanisms of toxicity. It discusses critical issues concerning the emergence of silver nanopesticides, spanning their mosquitocidal efficacy to environmental impact and safety considerations. While nano­silver has shown promise in targeting insect pests, there is a lack of systematic research comparing its effects on different arthropod subclasses. Moreover, factors influencing nanotoxicity, such as nanoparticle size, charge, and surface chemistry, require further investigation to optimize the design of eco-safe nanoparticles for pest control. By elucidating the mechanisms by which nanoparticles interact with pests and non-target organisms, we can enhance the specificity and effectiveness of nanopesticides while minimizing unintended ecological consequences.

Joint Modifiable Risk Factor Control and Incident Stroke in Hypertensive Patients.

Recent guidelines have recognized several factors, including blood pressure (BP), body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), hemoglobin A1c (HbA1c), smoking, and physical activity, as key contributors to stroke risk. However, the impact of simultaneous management of these risk factors on stroke susceptibility in individuals with hypertension remains ambiguous. This study involved 238 388 participants from the UK Biobank, followed up from their recruitment date until April 1, 2023. Cox proportional hazard models with hazard ratios (HRs) and 95% confidence intervals (CIs) were used to illustrate the correlation between the joint modifiable risk factor control and the stroke risk. As the degree of risk factor control increased, a gradual reduction in stroke risk was observed. Hypertensive patients who had the optimal risk factor control (≥5 risk factor controls) had a 14.6% lower stroke risk than those who controlled 2 or fewer (HR: 0.854; 95% CI: 804-0.908; p < 0.001). The excess risk of stroke linked to hypertension slowly diminished as the number of controlled risk factors increased. However, the risk was still 25.1% higher for hypertensive patients with optimal risk factor control as compared to the non-hypertensive population (HR: 1.251; 95% CI: 1.100-1.422; p < 0.001). The protective effect of joint risk factor control against the stroke risk due to hypertension was stronger in medicated hypertensive patients than in those not medicated. This finding leads to the conclusion that joint risk factor control combined with pharmacological treatment could potentially eliminate the excess risk of stroke associated with hypertension.

Extreme temperature events, functional dependency, and cardiometabolic multimorbidity: Insights from a national cohort study in China.

BACKGROUND: Extreme temperature events (ETEs), including heatwaves and cold spells, are attracting increasing attention because of their impacts on human health. However, the association between ETEs and cardiometabolic multimorbidity (CMM) and the role of functional dependency in this relationship remain unclear. METHODS: A prospective cohort study was conducted using data from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2020, considering 12 definitions each for heatwaves and cold spells, and three levels of functional dependency. Mixed Cox models with time-varying variables were used to comprehensively assess the independent and combined effects of ETEs and functional dependency on CMM. Additionally, subgroup analyses were conducted to investigate whether the relationship between ETEs and CMM was modified by the baseline characteristics. RESULTS: Heatwave and cold spell exposures were associated with an increased risk of CMM (HR range: 1.028-1.102 and 1.046-1.187, respectively). Compared to participants with normal functional abilities, the risk of CMM increased with higher levels of functional dependency (HR range: 1.938-2.185). ETEs exposure and functional dependency are jointly associated with CMM risk. Participants with high-intensity ETEs exposure and high functional dependency had the greatest risk of developing CMM. Participants aged 60 and above were more susceptible to the effects of ETEs on CMM. Additionally, urban residents and those in northern regions were more vulnerable to heatwaves. CONCLUSION: Both ETEs exposure and functional dependency increase the risk of developing CMM. Participants with functional dependency exposed to high-intensity ETEs faced the highest risk of developing CMM. These findings highlight the significant impact of ETEs on CMM and the importance of protecting vulnerable populations during periods of extreme temperature.

Association of free fatty acid in first trimester with the risk of gestational diabetes mellitus: a nested case-control study.

BACKGROUND: Accumulating evidence shows that free fatty acids (FFA) are associated with gestational diabetes mellitus (GDM). However, most of the studies focus on a few specific types of FFA, such as α-linolenic acid (C18:3n3) and Arachidonic acid (C20:4n6) or a total level of FFA. OBJECTIVE: This study aimed to test the association between a variety of FFAs during the first trimester and the risk of GDM. METHODS: The participants came from the Zhoushan Pregnant Women Cohort (ZWPC). A 1:2 nested case-control study was conducted: fifty mothers with GDM were matched with 100 mothers without GDM by age, pre-pregnancy body mass index (BMI), month of oral glucose tolerance test (OGTT) and parity. Thirty-seven FFAs (including 17 saturated fatty acids (SFA), 8 monounsaturated fatty acids (MUFA), 10 polyunsaturated fatty acids (PUFA) and 2 trans fatty acids (TFA)) in maternal plasma during the first trimester were tested by Gas Chromatography-Mass Spectrometry (GC-MS). Conditional logistic regression models were performed to assess the associations of FFA with the risk of GDM. RESULTS: Nine FFAs were respectively associated with an increased risk of GDM (P < 0.05), and four FFAs were respectively associated with a decreased risk of GDM (P < 0.05). SFA risk score was associated with a greater risk of GDM (OR = 1.34, 95% CI: 1.12-1.60), as well as UFA risk score (OR = 1.26, 95% CI: 1.11-1.44), MUFA risk score (OR = 1.70, 95%CI: 1.27-2.26), PUFA risk score (OR = 1.32, 95%CI: 1.09-1.59) and TFA risk score (OR = 2.51, 95%CI: 1.23-5.13). Moreover, joint effects between different types of FFA risk scores on GDM were detected. For instance, compared with those with low risk scores of SFA and UFA, women with high risk scores of SFA and UFA had the highest risk of GDM (OR = 8.53, 95%CI: 2.41-30.24), while the Odds ratio in those with a low risk score of SFA and high risk score of UFA and those with a high risk score of SFA and low risk score of UFA was 6.37 (95%CI:1.33- 30.53) and 4.25 (95%CI: 0.97-18.70), respectively. CONCLUSION: Maternal FFAs during the first trimester were positively associated with the risk of GDM. Additionally, there were joint effects between FFAs on GDM risk. CONDENSATION: Elevated FFA levels in the first trimester increased the risk of GDM.

Do interaction and joint effects between physical activity and dietary inflammatory index modify stroke risk?

OBJECTIVE: Stroke is a major public health threat, and both physical activity (PA) and diet are modifiable risk factors for stroke. This study assessed the interaction and joint effects of PA and the dietary inflammatory index (DII) on stroke. METHODS: We included 18,676 participants from the 2007-2020 National Health and Nutrition Examination Survey. The independent associations, interactions, and joint effects of PA and the DII on stroke were assessed by weighted multivariable logistic regression. RESULTS: The weighted mean age of the participants was 48.24 years, and comprised 703 individuals who had experienced a stroke. After adjusting for confounders, increased stroke risk was independently associated with a higher DII (Q4, odds ratio [OR]: 1.72, 95 % confidence interval [CI]: 1.27-2.34) and insufficient PA (inactive, OR: 1.37, 95 % CI: 1.05-1.78). No significant multiplicative (OR: 1.11, 95 % CI: 0.34-1.93) or additive (relative excess risk due to interaction: 0.45, 95 % CI: 0.35-1.25) interactions were found between DII and PA. The results of joint associations indicated that individuals who consumed the most pro-inflammatory diet (DII, Q4) and were physically inactive (OR: 2.39, 95 % CI: 1.61-3.56) had the highest stroke risk than those who consumed the most anti-inflammatory diet (DII, Q1) and were physically active. CONCLUSION: Active PA and low DII scores are independent protective factors against stroke. Although the multiplicative and additive effects of the DII and PA on stroke risk are not statistically significant, the analysis of their joint effects suggest that individuals who consume anti-inflammatory diets and exhibit active PA consistently have the lowest risk of stroke.

Estimating the impact of metabolic syndrome on low back pain and the joint effects of metabolic syndrome and depressive symptoms on low back pain: insights from the China Health and Retirement Longitudinal Study.

BACKGROUND: Although metabolic syndrome (MetS) and depressive symptoms (DS) are predictors of low back pain (LBP), their combined effects and relative contributions to LBP have not been well studied. Using the nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS), this study conducted cross-sectional and longitudinal analyses to investigate the impact of MetS on LBP, and the joint effects of MetS and DS on LBP. METHODS: This study included a cross-sectional analysis of 8957 participants aged at least 45 years from the CHARLS 2011 dataset and a longitudinal follow-up of 3468 participants without LBP from the CHARLS 2011, tracked over 9.25 years (from June 2011 to September 2020) with 4 times LBP assessment in CHARLS 2013, 2015, 2018, and 2020. To explore the association between MetS on LBP and the joint effects of MetS and DS on LBP, multivariable-adjusted multinomial logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Multivariable-adjusted COX proportional hazards regression models were applied to estimate hazard ratios (HRs) and 95% CIs. All statistical analyses were conducted using STATA (version SE16). RESULTS: In the cross-sectional analysis, MetS was associated with a lower risk of LBP (adjusted OR = 0.85, 95% CI = 0.74-0.97), while there was no significance for this association in the longitudinal analysis. In the joint association of MetS and DS with LBP, participants with NoMetS + DS (adjusted OR = 2.31, 95% CI = 1.94-2.75), and MetS + DS (adjusted OR = 2.16, 95% CI = 1.81-2.59) were risk factors for LBP events, while those with MetS + NoDS (adjusted OR = 0.75, 95% CI = 0.62-0.90) was a protective factor for LBP events than those with NoMetS + NoDS. During the 9.25 years of follow-up, 1708 cases (49.25%) experienced incident LBP events. In the longitudinal analysis, a significantly negative association was not found in MetS + NoDS for LBP events. Three sensitivity analyses identified the robustness of the associations. Moreover, the nature of cross-sectional associations differed by age (45-64 and 65 + years). CONCLUSIONS: Our study found that MetS was linked to a lower incidence of LBP, but this effect does not persist over time. Importantly, the combination of MetS and DS significantly increased LBP risk, a joint effect not extensively studied before. These findings underscore the novel contribution of our research, advocating for the joint assessment of MetS and DS to enhance LBP risk stratification and inform prevention strategies.

Associations between accelerometer-measured physical activity and sedentary behaviour with physical function among older women: a cross-sectional study.

BACKGROUND: This study aimed to investigate the relationships between accelerometer-measured physical activity (PA) and sedentary behaviour (SB) with physical function (PF) among older Chinese women in the community. METHODS: The present study comprised 1,113 community-dwelling older females, with an average age of 65 ± 2 years. We employed a linear regression analysis to investigate the relationship between patterns of PA and SB with PF. PA variables consisted of total PA time, bouted PA time (a continuous PA that lasts equal to or more than 10 min), and sporadic PA time (a continuous PA that lasts less than 10 min). SB variables included total SB time, 30-min bout of SB (a continuous SB that lasts equal to or more than 30 min), and 60-min bout of SB (a continuous SB that lasts equal to or more than 60 min). PF variables comprised handgrip strength (HGS), one-legged stance test with eyes closed (OLSTEC), usual walking speed (UWS), maximum walking speed (MWS) and chair-stand time (CT). To explore the joint effects of moderate-to-vigorous-intensity PA (MVPA) and SB on PF, we divided the duration of SB and MVPA participation in older women into different combinations: low MVPA & high SB, low MVPA & low SB, high MVPA & high SB, high MVPA & low SB. RESULTS: The study revealed a significant association between 30-min bout of SB and CT, which remained after adjusting for total MVPA time (P = 0.021). Both total MVPA and bouted MVPA were found to be positively associated with better UWS, MWS, CT, and PF Z-score. When the combination of low MVPA & high SB was used as a reference, the regression coefficients for PF ascended by 1.32 (P < 0.001) in the high MVPA & high SB group and by 1.13 (P < 0.001) in the high MVPA & low SB group. CONCLUSIONS: A significant association was observed between poorer lower limb function and prolonged, uninterrupted SB in older women, rather than with the total SB time. Concurrently, the insufficient engagement in MVPA may also be a crucial factor contributing to poorer PF in older women. Engaging in longer durations and higher intensity of PA, such as bouts of MVPA lasting a minimum of 10 min or longer, may contribute to better PF.

Assessing long-term effects of gaseous air pollution exposure on mortality in the United States using a variant of difference-in-differences analysis.

Long-term mortality effects of particulate air pollution have been investigated in a causal analytic frame, while causal evidence for associations with gaseous air pollutants remains extensively lacking, especially for carbon monoxide (CO) and sulfur dioxide (SO2). In this study, we estimated the causal relationship of long-term exposure to nitrogen dioxide (NO2), CO, SO2, and ozone (O3) with mortality. Utilizing the data from National Morbidity, Mortality, and Air Pollution Study, we applied a variant of difference-in-differences (DID) method with conditional Poisson regression and generalized weighted quantile sum regression (gWQS) to investigate the independent and joint effects. Independent exposures to NO2, CO, and SO2 were causally associated with increased risks of total, nonaccidental, and cardiovascular mortality, while no evident associations with O3 were identified in the entire population. In gWQS analyses, an interquartile range-equivalent increase in mixture exposure was associated with a relative risk of 1.067 (95% confidence interval: 1.010-1.126) for total mortality, 1.067 (1.009-1.128) for nonaccidental mortality, and 1.125 (1.060-1.193) for cardiovascular mortality, where NO2 was identified as the most significant contributor to the overall effect. This nationwide DID analysis provided causal evidence for independent and combined effects of NO2, CO, SO2, and O3 on increased mortality risks among the US general population.

Serum albumin and liver dysfunction mediate the associations between organophosphorus pesticide exposure and hypertension among US adults.

BACKGROUND: Human health is commonly threatened by organophosphorus pesticides (OPPs) due to their widespread use and biological characteristics. However, the combined effect of mixtures of OPPs metabolites on the risk of hypertension and potential mechanism remain limited. OBJECTIVES: To comprehensively investigate the effects between OPPs exposure on hypertension risk and explore and underlying mechanism among US general population. METHODS: This cross-sectional study collected US adults who had available data on urine OPPs metabolites (dialkyl phosphate compounds, DAPs) from the National Health and Nutrition Examination Survey (NHANES) to assess the relationships of DAPs with hypertension risk. Survey-weighted logistic regression, restricted cubic spline (RCS), and mixed exposure analysis models [weighted quantile sum regression (WQS) and Bayesian kernel machine regression (BKMR)] were used to analyze individual, dose-response and combined associations between urinary DAPs metabolites and hypertension risk, respectively. Mediation analysis determined the potential intermediary role of serum albumin and liver function in the above associations. RESULTS: Compared with the reference group, participants with the highest tertile levels of DEP, DMTP, DETP, and DMDTP experienced increased risk of hypertension by 1.21-fold (95%CI: 1.02-1.36), 1.20-fold (95%CI: 1.02-1.42), 1.19-fold (95%CI: 1.01-1.40), and 1.17-fold (95%CI: 1.03-1.43), respectively. RCS curve also showed positive exposure-response associations of individual DAPs with hypertension risk. WQS and BKMR analysis further confirmed DAP mixtures were significantly associated with increased risk of hypertension, with DEP identified as a major contributor to the combined effect. Mediation analysis indicated that serum albumin and AST/ALT ratios played crucial mediating roles in the relationships between individual and mixed urinary DAPs and the prevalence of hypertension. CONCLUSION: Our findings provided more comprehensive and novel perspectives into the individual and combined effects of urinary OPPs matabolites on the increased risk of hypertension and the possible driving mechanism, which would be of great significance for environmental control and early prevention of hypertension.

Association of heavy metals exposure with lower blood pressure in the population aged 8-17 years: a cross-sectional study based on NHANES.

Background: The existing evidence regarding the joint effect of heavy metals on blood pressure (BP) in children and adolescents is insufficient. Furthermore, the impact of factors such as body weight, fish consumption, and age on their association remains unclear. Methods: The study utilized original data from the National Health and Nutrition Examination Survey, encompassing 2,224 children and adolescents with complete information on 12 urinary metals (barium, cadmium, cobalt, cesium, molybdenum, lead, antimony, thallium, tungsten, uranium, mercury and arsenic), BP, and core covariates. Various statistical methods, including weighted multiple logistic regression, linear regression, and Weighted Quantile Sum regression (WQS), were employed to evaluate the impact of mixed metal exposure on BP. Sensitivity analysis was conducted to confirm the primary analytical findings. Results: The findings revealed that children and adolescents with low-level exposure to lead (0.40 µg/L, 95%CI: 0.37, 0.42), mercury (0.38 µg/L, 95%CI: 0.35, 0.42) and molybdenum (73.66 µg/L, 95%CI: 70.65, 76.66) exhibited reduced systolic blood pressure (SBP) and diastolic blood pressure (DBP). Conversely, barium (2.39 µg/L, 95%CI: 2.25, 2.54) showed a positive association with increased SBP. A 25th percentile increase in the WQS index is significantly associated with a decrease in SBP of 0.67 mmHg (95%CI, -1.24, -0.10) and a decrease in DBP of 0.59 mmHg (95% CI, -1.06, -0.12), which remains statistically significant even after adjusting for weight. Furthermore, among individuals who consume fish, heavy metals have a more significant influence on SBP. A 25 percentile increase in the WQS index is significantly associated with a decrease of 3.30 mmHg (95% CI, -4.73, -1.87) in SBP, primarily attributed to mercury (27.61%), cadmium (27.49%), cesium (17.98%), thallium (8.49%). The study also identified a declining trend in SBP among children aged 10-17, whereas children aged 11-18 exhibited lower levels of systolic and diastolic blood pressure, along with a reduced risk of hypertension. Conclusion: Some heavy metals demonstrate an inverse association with the BP of children and adolescents, particularly notable in groups with fish consumption and older children and adolescents. Future studies are warranted to validate these findings and delve deeper into the interplay of heavy metals.

Association of prenatal multiple metal exposures with child neurodevelopment at 3 years of age: A prospective birth cohort study.

Prenatal exposures to toxic metals and trace elements have been linked to childhood neurodevelopment. However, existing evidence remains inconclusive, and further research is needed to investigate the mixture effects of multiple metal exposures on childhood neurodevelopment. We aimed to examine the associations between prenatal exposure to specific metals and metal mixtures and neurodevelopment in children. In this prospective cohort study, we used the multivariable linear regressions and the robust modified Poisson regressions to explore the associations of prenatal exposure to 25 specific metals with neurodevelopment among children at 3 years of age in 854 mother-child pairs from the Jiangsu Birth Cohort (JBC) Study. The Bayesian kernel machine regression (BKMR) was employed to assess the joint effects of multiple metals on neurodevelopment. Prenatal manganese (Mn) exposure was negatively associated with the risk of non-optimal cognition development of children, while vanadium (V), copper (Cu), zinc (Zn), antimony (Sb), cerium (Ce) and uranium (U) exposures were positively associated with the risk of non-optimal gross motor development. BKMR identified an interaction effect between Sb and Ce on non-optimal gross motor development. Additionally, an element risk score (ERS), representing the mixture effect of multiple metal exposures including V, Cu, Zn, Sb, Ce and U was constructed based on weights from a Poisson regression model. Children with ERS in the highest tertile had higher probability of non-optimal gross motor development (RR = 2.37, 95 % CI: 1.15, 4.86) versus those at the lowest tertile. Notably, Sb [conditional-posterior inclusion probabilities (cPIP) = 0.511] and U (cPIP = 0.386) mainly contributed to the increased risk of non-optimal gross motor development. The findings highlight the importance of paying attention to the joint effects of multiple metals on children's neurodevelopment. The ERS score may serve as an indicator of comprehensive metal exposure risk for children's neurodevelopment.

Association Between Exposure to Multiple Toxic Metals in Follicular Fluid and the Risk of PCOS Among Infertile Women: The Mediating Effect of Metabolic Markers.

Polycystic ovary syndrome (PCOS) severely affects women's fertility and accompanies serious metabolic disturbances, affecting 5%-20% of women of reproductive age globally. We previously found that exposure to toxic metals in the blood raised the risk of PCOS, but the association between exposure to toxic metals and the risk of PCOS in the follicular fluid, the microenvironment for oocyte growth and development in females, and its effect on metabolism has not been reported. This study aimed to evaluate the associations between the concentrations of cadmium (Cd), mercury (Hg), barium (Ba) and arsenic (As) in FF and the risk of PCOS, and to explore the mediating effect of metabolic markers in FF on the above relationship. We conducted a case-control study, including 557 women with PCOS and 651 controls. Ba, Cd, Hg and As levels in FF were measured by ICP-MS, metabolites levels in FF was measured by LC-MS/MS among 168 participants randomly selected from all the participants. Logistic regression models were used to assess the association of a single metal level with the PCOS risk, and linear regression models were used to assess the relationships of a single metal level with clinical phenotype parameters and metabolites levels. Combined effect of metals mixture levels on the risk of PCOS were assessed via weighted quantile sum (WQS) regression and bayesian kernel machine regression (BKMR). Medication analysis was performed to explore the role of metabolic markers on the relationship of toxic metals levels with the risk of PCOS. The exposure levels of Cd, Hg, Ba and As in FF were all positively and significantly associated with the PCOS risk (with respect to the highest vs. lowest tertile group: OR = 1.57, 95% CI = 1.17 ~ 2.12 for Cd, OR = 1.69, 95% CI = 1.22 ~ 2.34 for Hg, OR = 1.76, 95% CI = 1.32 ~ 2.34 for Ba, OR = 1.42, 95% CI = 1.05 ~ 1.91 for As). In addition, levels of metal mixture also significantly correlated with the risk of PCOS, Cd level contributed most to it. Moreover, we observed significant positive relationships between Cd level and LH (ß = 0.048, 95% CI = 0.002 ~ 0.094), T (ß = 0.077, 95% CI = 0.029 ~ 0.125) and HOMA-IR value (ß = 0.060, 95% CI = 0.012 ~ 0.107), as well as Hg level with LH, FSH/LH ratio and TC. Furthermore, we revealed that estrone sulfate, LysoPE 22:6 and N-Undecanoylglycine were significantly and positively mediating the association between Cd level and the risk of PCOS (with mediated proportion of 0.39, 0.24 and 0.35, respectively), and between Hg level and the risk of PCOS (with mediated proportion of 0.29, 0.20 and 0.46, respectively). These highly expressed metabolites significantly enriched in the fatty acid oxidation, steroid hormone biosynthesis and glycerophospholipids metabolism, which may explain the reason why the levels of Cd and Hg in FF associated with the phenotype of PCOS. Ba and As in FF was not found the above phenomenon. Our results suggested that exposure to multiple toxic metals (Cd, Hg, Ba and As) in FF associated with the increased risk of PCOS, Cd was a major contributor. Levels of Cd and Hg in FF significantly associated with the phenotype of PCOS. The above association may result from that Cd and Hg in FF related with the disturbance of fatty acid oxidation, steroid hormone biosynthesis and the glycerophospholipids metabolism.

Complex interplay of heavy metals and renal injury: New perspectives from longitudinal epidemiological evidence.

BACKGROUND: Epidemiological studies have reported associations between heavy metals and renal function. However, longitudinal studies are required to further validate these associations and explore the interactive effects of heavy metals on renal function and their directional influence. METHOD: This study, conducted in Northeast China from 2016 to 2021, included a four-time repeated measures design involving 384 participants (1536 observations). Urinary concentrations of chromium (Cr), cadmium (Cd), manganese (Mn), and lead (Pb) were measured, along with renal biomarkers including urinary microalbumin (umAlb), urinary albumin-to-creatinine ratio (UACR), N-acetyl-ß-D-glucosaminidase (NAG), and ß2-microglobulin (ß2-MG) levels. Estimated glomerular filtration rate (eGFR) was calculated. A Linear Mixed Effects Model (LME) examined the association between individual metal exposure and renal biomarkers. Subsequently, Quantile g-computation and Bayesian Kernel Machine Regression (BKMR) models assessed the overall effects of heavy metal mixtures. Marginal Effect models examined the directional impact of metal interactions in the BKMR on renal function. RESULT: Results indicate significant impacts of individual and combined exposures of Cr, Cd, Pb, and Mn on renal biomarkers. Metal interactions in the BKMR model were observed, with synergistic effects of Cd-Cr on NAG, umAlb, UACR; Cd-Pb on NAG, UACR; Pb-Cr on umAlb, UACR, eGFR-MDRD, eGFR-EPI; and an antagonistic effect of Mn-Pb-Cr on UACR. CONCLUSION: Both individual and combined exposures to heavy metals are associated with renal biomarkers, with significant synergistic interactions leading to renal damage. Our findings elucidate potential interactions among these metals, offering valuable insights into the mechanisms linking multiple metal exposures to renal injury.

Independent and Joint Effects of Prenatal Incense-Burning Smoke Exposure and Children's Early Outdoor Activity on Preschoolers' Obesity.

Incense burning is a significant source of indoor air pollution in many Asian regions. There is emerging evidence that maternal prenatal exposure to incense-burning smoke may be a risk factor for childhood obesity. We aimed to extend this new line of research by investigating the independent and joint effect of incense-burning smoke exposure, and children's outdoor activity in early life, on preschoolers' obesity. A total of 69,637 mother-child dyads were recruited from all kindergartens in the Longhua District of Shenzhen, China. Information on sociodemographic characteristics, maternal exposure to incense-burning smoke (IBS) during pregnancy, and frequency and duration of outdoor activity at the age of 1-3 years was collected by a self-administered questionnaire. In addition, the heights and weights of the children were measured by the research team. Logistic regression models and cross-over analyses were conducted to investigate the independent and combined effects of maternal exposure to incense-burning smoke during pregnancy and children's early outdoor activity on obesity in preschoolers. We found that prenatal exposure to incense-burning smoke increased the risk of the presence of obesity in preschoolers' (AOR = 1.13, 95% CI = 1.03-1.23). Additionally, lower frequencies (<3 times/week) or shorter durations (<60 min/time) of outdoor activity from the age of 1-3 years were significantly associated with the presence of obesity, with AORs of 1.24 (95% CI =1.18-1.32) and 1.11 (95% CI = 1.05-1.17), respectively. Furthermore, the cross-over analysis showed that prenatal exposure to IBS combined with a lower frequency of early outdoor activity (AOR = 1.47, 95% CI = 1.31-1.66) or a shorter duration of outdoor activity during ages of 1-3 years (AOR = 1.22, 95% CI = 1.07-1.39) increased the risk of obesity in preschoolers. Finally, additive interactions between prenatal exposure to IBS and postnatal outdoor activity on obesity were identified. Our study indicates that maternal exposure to incense-burning smoke during pregnancy and early lower postanal outdoor activity may independently and jointly increase the risk of obesity among preschoolers.

Joint effect of long-term exposure to ambient air pollution on the prevalence of chronic obstructive pulmonary disease using the Korea National Health and Nutrition Examination Survey 2010-2019.

BACKGROUND: Little is known about the relationship between long-term joint exposure to mixtures of air pollutants and the prevalence of chronic obstructive pulmonary disease (COPD). We aimed to assess the joint impact of long-term exposure to ambient air pollution on the prevalence of COPD in Korea, especially in areas with high levels of air pollution. METHODS: We included 22,387 participants who underwent spirometry tests in 2010-2019. The community multiscale air quality model was used to estimate the levels of ambient air pollution at residential addresses. The average exposure over the 5 years before the examination date was used to calculate the concentrations of air pollution. Forced expiratory volume in 1 s and forced vital capacity were used to define restrictive lung disease, COPD, and moderate-to-severe COPD. Quantile-based g-computation models were used to assess the joint impact of air pollution on COPD prevalence. RESULTS: A total of 2535 cases of restrictive lung disease, 2787 cases of COPD, and 1399 cases of moderate-to-severe COPD were identified. In the individual pollutant model, long-term exposure was significantly associated with both restrictive lung disease and COPD. In the mixture pollutant model, the odds ratios (ORs, 95% confidence intervals) for restrictive lung disease increased with each quartile increment in the 1- to 5-year average mixtures: 1.14 (1.02-1.28, 1 year), 1.25 (1.11-1.41, 2 years), 1.26 (1.11-1.42, 3 years), 1.32 (1.16-1.51, 4 years), and 1.37 (1.19-1.58, 5 years), respectively. The increase in ORs of restrictive lung disease accelerated over time. By contrast, the ORs of COPD showed a decreasing trend over time. CONCLUSIONS: Long-term exposure to air pollutants, both individually and jointly, was associated with an increased risk of developing COPD, particularly restrictive lung disease. Our findings highlight the importance of comprehensively assessing exposure to various air pollutants in relation to COPD.

Association of multiple serum minerals and vitamins with metabolic dysfunction-associated fatty liver disease in US adults: National Health and Nutrition Examination Survey 2017-2018.

Background: Despite the rapid increase in the global prevalence of Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD), there are no approved therapeutic drugs for MAFLD yet. Nutrient supplementation might mitigate the risk of MAFLD. It is more typical for individuals to consume multiple nutrients simultaneously. However, the studies exploring the combined effects of multiple nutrients on MAFLD are limited. This study aimed to investigate the relationship between both individual nutrients and their combined influence on the risk of MAFLD. Methods: Data were obtained from National Health and Nutrition Examination Survey (NHANES), and 18 types of nutrients were considered in this study. Logistic regression analysis was performed to evaluate the correlation between single nutrients and the risk of MAFLD. The Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was performed to pinpoint the most relevant nutrient associated with the risk of MAFLD. Subsequently, both Weighted Quantile Sum (WQS) regression and Quantile g-computation (Qgcomp) were used to assess the combined effects of multiple nutrients on the risk of MAFLD. Results: A total of 3,069 participants were included in this study. LASSO regression analysis showed that Se, α-tocopherol, and γ-tocopherol exhibited a positive association with the risk of MAFLD. In contrast, the serum levels of Co, P, α-cryptoxanthin, LZ, and trans-ß-carotene were inversely associated with the prevalence of MAFLD. When Se and two types of vitamin E were excluded, the WQS index showed a significant inverse relationship between the remaining 15 nutrients and the risk of MAFLD; α-cryptoxanthin showed the most substantial contribution. Similarly, Qgcomp suggested that the combined effects of these 15 nutrients were associated with a lower risk of MAFLD, with α-cryptoxanthin possessing the most significant negative weights. Conclusion: This study suggested that the complex nutrients with either a low proportion of Se, α-tocopherol, and γ-tocopherol or without them should be recommended for patients with MAFLD to reduce its risk.

Joint and interactive effects of metal mixtures on liver damage: Epidemiological evidence from repeated-measures study.

BACKGROUND: The impact of heavy metals on liver function has been examined in numerous epidemiological studies. However, these findings lack consistency and longitudinal validation. METHODS: In this study, we conducted three follow-up surveys with 426 participants from Northeast China. Blood and urine samples were collected, along with questionnaire information. Urine samples were analyzed for concentrations of four metals (chromium [Cr], cadmium [Cd], lead [Pb], and manganese [Mn]), while blood samples were used to measure five liver function indicators (alanine aminotransferase [ALT], aspartate aminotransferase [AST], albumin [ALB], globulin [GLB], and total protein [TP]). We utilized a linear mixed-effects model (LME) to explore the association between individual heavy metal exposure and liver function. Joint effects of metal mixtures were investigated using quantile g-computation and Bayesian kernel machine regression (BKMR). Furthermore, we employed BKMR and Marginal Effect models to examine the interaction effects between metals on liver function. RESULTS: The LME results demonstrated a significant association between urinary heavy metals (Cr, Cd, Pb, and Mn) and liver function markers. BKMR results indicated positive associations between heavy metal mixtures and ALT, AST, and GLB, and negative associations with ALB and TP, which were consistent with the g-comp results. Synergistic effects were observed between Cd-Cr on ALT, Mn-Cr and Cr-Pb on ALB, while an antagonistic effect was found between Mn-Pb and Mn-Cd on ALB. Additionally, synergistic effects were observed between Mn-Cr on GLB and Cd-Cr on TP. Furthermore, a three-way antagonistic effect of Mn-Pb-Cr on ALB was identified. CONCLUSION: Exposure to heavy metals (Cr, Cd, Mn, Pb) is associated with liver function markers, potentially leading to liver damage. Moreover, there are joint and interaction effects among these metals, which warrant further investigation at both the population and mechanistic levels.

Incorporating genetic similarity of auxiliary samples into eGene identification under the transfer learning framework.

BACKGROUND: The term eGene has been applied to define a gene whose expression level is affected by at least one independent expression quantitative trait locus (eQTL). It is both theoretically and empirically important to identify eQTLs and eGenes in genomic studies. However, standard eGene detection methods generally focus on individual cis-variants and cannot efficiently leverage useful knowledge acquired from auxiliary samples into target studies. METHODS: We propose a multilocus-based eGene identification method called TLegene by integrating shared genetic similarity information available from auxiliary studies under the statistical framework of transfer learning. We apply TLegene to eGene identification in ten TCGA cancers which have an explicit relevant tissue in the GTEx project, and learn genetic effect of variant in TCGA from GTEx. We also adopt TLegene to the Geuvadis project to evaluate its usefulness in non-cancer studies. RESULTS: We observed substantial genetic effect correlation of cis-variants between TCGA and GTEx for a larger number of genes. Furthermore, consistent with the results of our simulations, we found that TLegene was more powerful than existing methods and thus identified 169 distinct candidate eGenes, which was much larger than the approach that did not consider knowledge transfer across target and auxiliary studies. Previous studies and functional enrichment analyses provided empirical evidence supporting the associations of discovered eGenes, and it also showed evidence of allelic heterogeneity of gene expression. Furthermore, TLegene identified more eGenes in Geuvadis and revealed that these eGenes were mainly enriched in cells EBV transformed lymphocytes tissue. CONCLUSION: Overall, TLegene represents a flexible and powerful statistical method for eGene identification through transfer learning of genetic similarity shared across auxiliary and target studies.

Joint Effect of Physical Activity and Sedentary Behavior with the Female Urinary Incontinence: An Analysis of NHANES 2011-2016.

INTRODUCTION: Our study aimed to assess the independent and joint effects of leisure-time physical activity and sedentary behavior with urinary incontinence (UI). METHODS: Data were obtained from the National Health and Nutrition Examination Survey 2011-2016. The primary endpoint was the risk of different subtypes of UI, including stress UI, urgency UI, and mixed UI. The primary exposures were leisure-time physical activity and sedentary behavior. Sedentary behavior was assessed by screen time. Weighted univariate and multivariate logistic regression models were used to observe the independent and joint relationship of leisure-time physical activity and sedentary behavior with UI risk (including stress UI, urgency UI, and mixed UI). RESULTS: In total, 6,927 female participants were included in this analysis. 3,377 females did not have UI, 1,534 had stress UI, 836 had urgency UI, and 1,180 had mixed UI. Screen time with ≥5 h/day was associated with increased odds of urgency UI (odds ratio [OR] = 1.31, 95% confidence intervals (CI): 1.06-1.61), which indicated the relationship of sedentary behavior and urgency UI. Engaging in leisure-time physical activity with of ≥750 metabolic equivalent (MET)·min/week was found to be significantly associated with reduced likelihood of mixed UI (OR = 0.68, 95% CI: 0.55-0.85). Additionally, the interaction term of leisure-time physical activity<750 MET·min/week and screen time ≥5 h/day was observed to be linked with increased odds of urgency and mixed UI. CONCLUSION: Participants experiencing a lower level of leisure-time physical activity and a higher level of sedentary behavior together might enhance the urgency and mixed UI risk.

The joint effects of mixture exposure to multiple meteorological factors on step count: A panel study in China.

The public health burden of increasing extreme weather events has been well documented. However, the influence of meteorological factors on physical activity remains limited. Existing mixture effect methods cannot handle cumulative lag effects. Therefore, we developed quantile g-computation Distributed lag non-linear model (QG-DLNM) by embedding a DLNM into quantile g-computation to allow for the concurrent consideration of both cumulated lag effects and mixture effects. We gathered repeated measurement data from Henan Province in China to investigate both the individual impact of meteorological factor on step counts using a DLNM, and the joint effect using the QG-DLNM. We projected future step counts linked to changes in temperature and relative humidity driven by climate change under three scenarios from the sixth phase of the Coupled Model Intercomparison Project. Our findings indicate there are inversed U-shaped associations for temperature, wind speed, and mixture exposure with step counts, peaking at 11.6 °C in temperature, 2.7 m/s in wind speed, and 30th percentile in mixture exposure. However, there are negative associations between relative humidity and rainfall with step counts. Additionally, relative humidity possesses the highest weights in the joint effect (49% contribution). Compared to 2022s, future step counts are projected to decrease due to temperature changes, while increase due to relative humidity changes. However, when considering both future temperature and humidity changes driven by climate change, the projections indicate a decrease in step counts. Our findings may suggest Chinese physical activity will be negatively influenced by global warming.