STUDY QUESTION:Are reproductive factors associated with biological aging, and does biological aging mediate the associations of reproductive factors with premature mortality? SUMMARY ANSWER:Multiple reproductive factors are related to phenotypic age acceleration (PhenoAge-Accel), while adherence to a healthy lifestyle mitigates these harmful effects; PhenoAge-Accel mediated the associations between reproductive factors and premature mortality. WHAT IS KNOWN ALREADY:Accelerated aging is a key contributor to mortality, but knowledge about the effect of reproductive factors on aging is limited. STUDY DESIGN, SIZE, DURATION:This prospective cohort study included 223 729 women aged 40-69 years from the UK biobank in 2006-2010 and followed up until 12 November 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS:Reproductive factors were collected through a touchscreen questionnaire. Biological aging was assessed through PhenoAge-Accel. Multiple linear regression models were used to examine the relationships of reproductive factors with PhenoAge-Accel and estimate the modified effect of a healthy lifestyle. Furthermore, we applied mediation analysis to explore the mediating role of PhenoAge-Accel in the associations between reproductive factors and premature mortality. MAIN RESULTS AND THE ROLE OF CHANCE:Early menarche (<12 years vs 13 years, β: 0.37, 95% CI: 0.30, 0.44), late menarche (≥15 years vs 13 years, β: 0.18, 95% CI: 0.11, 0.25), early menopause (<45 years vs 50-51 years, β: 0.62, 95% CI: 0.51, 0.72), short reproductive lifespan (<30 years vs 35-39 years, β: 0.81, 95% CI: 0.70, 0.92), nulliparity (vs two live births, β: 0.36, 95% CI: 0.30, 0.43), high parity (≥4 vs 2 live births, β: 0.49, 95% CI: 0.40, 0.59), early age at first live birth (<20 years vs 25-29 years, β: 0.66, 95% CI: 0.56, 0.75), and stillbirth (β: 0.51, 95% CI: 0.36, 0.65) were associated with increased PhenoAge-Accel. Furthermore, PhenoAge-Accel mediated 6.0%-29.7% of the associations between reproductive factors and premature mortality. Women with an unfavorable lifestyle and reproductive risk factors had the highest PhenoAge-Accel compared to those with a favorable lifestyle and without reproductive risk factors. LIMITATIONS, REASONS FOR CAUTION:The participants in the UK Biobank were predominantly of White ethnicity; thus, caution is warranted when generalizing these findings to other ethnic groups. WIDER IMPLICATIONS OF THE FINDINGS:Our findings reveal the harmful effects of multiple reproductive factors on biological aging and the mediating role of biological aging in the associations between reproductive factors and premature mortality. They highlight the significance of adhering to a healthy lifestyle to slow biological aging as a potential way to reduce premature mortality among women with reproductive risk factors. STUDY FUNDING/COMPETING INTEREST(S):This study was funded by the National Natural Science Foundation of China (82003479, 82073660, 72204215), Hubei Provincial Natural Science Foundation of China (2023AFB663), Zhejiang Province Public Welfare Technology Application Research Project (GF22H269155), and China Postdoctoral Science Foundation (2019M662646, 2020T130220). The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER:N/A.

Objective To investigate associations of ideal cardiovascular health behaviors with arterial stiffness and its progression in adults for providing a reference to the prevention and treatment of cardiovascular diseases.Methods A questionnaire survey,physical examination,laboratory tests,and brachial-ankle pulse wave velocity(baPWV)measure-ment were conducted among 5 536 adult physical examinees recruited through convenient sampling in a general hospital located in Wuhan city,Hubei province from August 2018 to May 2019.The evaluation of cardiovascular health behavior was performed using an integrated overall score that encompassed smoking,dietary pattern,exercise routine,body mass index(BMI),blood pressure,fasting plasma glucose,and total cholesterol level.Among the surveyed participants who had complete information and no history of cardiovascular disease at baseline(n=2 683),a follow-up baPWV measurement was conducted approximately two years later from June 2019 to February 2022.From this follow-up group of individuals with valid data for both baPWV measurements and baseline values below or equal to 1400 cm/s(n=372),an analysis was conducted to investigate factors influencing the progression of arterial stiffness.An unconditional multivariate logistic regression model was employed to explore the correlations between ideal cardiovascular health behaviors and arterial hardening as well as its progression.Results Among the 2 683 individuals without a history of cardiovascular disease at baseline survey,34.03％,48.16％,and 17.81％were assessed as having ideal,general,and poor cardiovascular health behaviors or factors respectively,while 31.83％were detected with arterial stiffness indicated by baPWV ≥ 1 400 cm/s.In contrast,among the 372 individuals with the two baPWV measurements and without baseline arterial stiffness(baPWV＜1 400 cm/s),the proportions of having ideal,general,and poor cardiovascular health behaviors were 43.55％,42.74％,and 13.71％respectively;meanwhile,progressive arterial stiffness was observed in approximately one-fifth of them according to elevated baPWV values(≥1 400 cm/s).After adjusting for confounding factors such as gender,age,education level and family history of cardiovascular disease using multivariate logistic regression analysis method,the results showed that compared to those with poor cardiovascular health behavior or factors,individuals who had ideal or general cardiovascular health behavior had significantly decreased risk of developing arterial stiffness with odds ratios(OR)being equal to 0.28(95％confidence interval[95％CI]:0.21-0.37)and 0.64(95％CI:0.51-0.81),respectively.Further adjustment for baseline baPWV values revealed that the risk of progressive arterial stiffness significantly decreased(OR=0.29,95％CI:0.11-0.73)in individuals who had ideal rather than poor cardiovascular health behaviors.Conclusion The ideal cardiovascular health behavior and factor scores exhibit a significant negative correlation with the occurrence and progression of arterial stiffness among Chinese adults.Moreover,early intervention aimed at promoting ideal cardiovascular health behavior and factors has the potential to effectively delay the onset and development of arterial stiffness.

AIM:To comprehensively examine the associations of childhood and adulthood body size, and child-to-adult body size change with adult leucocyte telomere length (LTL). METHODS:We included 453 602 participants from the UK Biobank. Childhood body size at the age of 10 years was collected through a questionnaire. Adulthood body size was assessed using body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), fat mass index (FMI), and fat-free mass index (FFMI). RESULTS:Individuals with plumper body size in childhood exhibited shorter LTL in adulthood (-0.0086 [-0.0017, -0.0004]). Adulthood BMI (-0.0286 [-0.0315, -0.0258]), WC (-0.0271 [-0.0303, -0.0238]), WHR (-0.0269 [-0.0308, -0.0230]) and FMI (-0.0396 [-0.0438, -0.0351]) were negatively associated with LTL, whereas FFMI (0.0095 [0.0039, 0.0152]) was positively associated with LTL. Compared to individuals consistently having an average/normal weight in both childhood and adulthood, those who maintained or developed overweight/obesity from childhood to adulthood had a shorter adult LTL, regardless of childhood body size. Notably, the LTL shortening effect was not observed in individuals with plumper body size in childhood but normal weight in adulthood. CONCLUSIONS:Childhood and adulthood obesity are both associated with LTL shortening in adulthood. Transitioning to or maintaining overweight/obese status from childhood to adulthood is associated with shorter adult LTL, whereas this effect can be reversed if plumper children become normal weight.

Previous studies have shown that higher hemoglobin A1c (HbA1c) levels within the normal range during pregnancy can increase the risk of adverse birth outcomes. However, the effects of the longitudinal HbA1c trajectory during pregnancy on adverse birth outcomes among non-gestational diabetic women are poorly characterized. We aimed to identify HbA1c trajectory during pregnancy among non-gestational diabetic women and to estimate their associations with adverse birth outcomes. Data was extracted from the Information System of Guangdong Women and Children Hospital, China, from January 2017 to July 2022. This study involved 13,979 women who did not have gestational diabetes mellitus and underwent repeated HbA1c measurements during pregnancy. Latent mixture modeling was used to identify HbA1c trajectory groups. Logistic regression was applied to explore the associations between HbA1c trajectory groups and adverse birth outcomes, including preterm delivery, low birth weight, macrosomia, small for gestational age, and large for gestational age (LGA). Three HbA1c trajectory groups were identified: low-stable (range 4.0

Exposure to metals has been related to alterations in leukocyte telomere length (LTL), an aging marker. However, the evidence regarding this relationship in children and adolescents, as well as the underlying mechanisms, remains unclear. Therefore, we aimed to explore the individual and mixture effects of metals on LTL in children and adolescents and to assess the mediating role of thyroid hormones and the modifying effect of a healthy lifestyle. In a cross-sectional study performed in Liuzhou, China, we assessed 5 serum thyroid hormones, 18 urinary metals, and LTL among 1050 children and adolescents aged 6-18 years. We employed multivariate linear regression and weighted quantile sum (WQS) regression to assess the associations of urinary metals with LTL in children and adolescents. Mediation analyses were conducted to explore the effects of thyroid hormones on these relationships. Urinary cobalt (Co), nickel (Ni), strontium (Sr), mercury (Hg), cadmium (Cd), and thallium (Tl) were related to a shorter LTL in children and adolescents. The WQS regression showed a 6.31% (95% CI: -8.76%, -3.79%) decrease in LTL per quartile increase in the WQS index, and identified Ni (23.3%), Sr (21.7%), and Tl (18.0%) as the major contributors. Mediation analyses showed that triiodothyronine (T3) mediated 14.8% and 8.1% of the associations of urinary Sr and Hg with LTL, respectively, and suppressed 9.3% of the association with urinary Co. Furthermore, the inverse associations of Sr, Cd, and Tl with LTL were attenuated among participants who adopted a healthy lifestyle. Our findings suggested that exposure to Co, Ni, Sr, Cd, Hg, Tl, and their mixture were related to a shorter LTL in children and adolescents, potentially mediated by thyroid hormones. Additionally, adopting a healthy lifestyle may alleviate these adverse effects.

BACKGROUND:Previous research has investigated the hepatotoxicity of single metal exposure. However, there is limited evidence about metal mixture and their association with metabolic dysfunction-associated fatty liver disease (MAFLD), particularly in the Chinese population. OBJECTIVE:To investigate the individual and combine effects of 20 metals on MAFLD in a large population in China. METHODS:This study included 3651 participants from the Medical Physical Examination Center of Tongji Hospital, Wuhan, China. MAFLD was identified based on ultrasonic graphic evidence of hepatic steatosis and the presence of overweight/obese, diabetes mellitus, or metabolic dysregulation. Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine urinary concentrations of 20 metals. Logistic regression was used to assess the relationship between individual metal and MAFLD, with results presented as odds ratios (ORs) and 95 % confidence intervals (CIs). Weighted quantile sum (WQS) regression was performed to evaluate the combine effect of metals. RESULTS:The prevalence of MAFLD among the participants was 32.1 % (1173/3651). In singe-metal analysis, high exposure to zinc (OR =1.42; 95 % CI = 1.27, 1.59) and selenium (OR = 1.23; 95 % CI = 1.10, 1.39) were positively associated with MAFLD. No significant association was found for other metals. WQS regression analysis showed that urinary metal mixture was positively associated with MAFLD (OR = 1.32, 95 % CI: 1.15, 1.51), with zinc (50.4 %) being the largest contributor, followed by barium (10.8 %). CONCLUSIONS:In conclusion, our finding suggested that exposure to the mixture of metals was positively correlated with MAFLD, with zinc being the major contributor.

Aim To explore the relationships of multiple reproductive factors with type 2 diabetes mellitus (T2DM) risk and the joint effects of reproductive factors and genetic susceptibility. Methods We included 262,368 women without prevalent T2DM from the UK biobank. Cox proportional hazards regression models were employed to estimate the relationships of reproductive factors with T2DM risk and the joint effects of reproductive factors and genetic susceptibility. Results During a mean follow-up of 12.2 years, 8,996 T2DM cases were identified. Early menarche (<12 years, hazard ratio (HR) 1.08 [95 % confidence interval (CI) 1.02;1.13]), late menarche (≥15 years, HR 1.11 [1.04;1.17]), early menopause (<45 years, HR 1.20 [1.12;1.29]), short reproductive lifespan (<30 years, HR 1.25 [1.16;1.35]), hysterectomy (1.31, HR [1.23;1.40]), oophorectomy (HR 1.28 [1.20;1.36]), high parity (≥4, HR 1.25 [1.17;1.34]), early age at first live birth (<20 years, HR 1.23 [1.16;1.31]), miscarriage (HR 1.13 [1.07;1.19]), stillbirth (HR 1.14 [1.03;1.27]), and ever used hormonal replacement therapy (HR 1.19 [1.14;1.24]) were related to a higher T2DM risk, while ever used oral contraceptives (HR 0.93 [0.89;0.98]) was related to a lower T2DM risk. Furthermore, women with reproductive risk factors and high genetic risk had the highest T2DM risk compared to those with low genetic risk and without reproductive risk factors. Conclusion Our findings show that multiple reproductive factors are related to T2DM risk, particularly in women with high genetic risk.

Previous studies about metal exposures and bone mineral density (BMD) have mainly focused on individual metals. The objective of this study was to explore the association of single and multiple metal exposures with BMD among Chinese adults. We recruited 2922 participants from Tongji Hospital in Wuhan, China. The urinary concentrations of 21 metals were measured by the inductively coupled plasma mass spectrometer. BMD was measured using dual-energy X-ray absorptiometry. We applied linear regression and Bayesian kernel machine regression (BKMR) to examine the association of single and multiple metal exposure with BMD, respectively. The linear regression model showed that cadmium (Cd) and strontium (Sr) were associated with lower BMD (all P-trend < 0.05). Compared with the lowest quantiles, the β (95

Previous studies have suggested an adverse association between exposure to organophosphate esters (OPEs) and metabolic disorders. However, there is still limited evidence regarding the link between OPEs and metabolic dysfunction-associated fatty liver disease (MAFLD). Moreover, it remains uncertain whether the impact of OPEs on MAFLD is consistent across genders. This study aimed to investigate the associations of OPEs with MAFLD and to explore potential gender differences in these associations. We recruited 1863 participants from Wuhan, China, and measured the levels of fifteen urinary OPE metabolites. Logistic regression and weighted quantile sum (WQS) regression were utilized for single-pollutant and multi-pollutant analysis, respectively. Moreover, stratified and interaction analyses were performed to assess potential sex-specific associations. The results of single-pollutant analysis showed that participants in the highest tertile of BCIPHIPP (OR = 1.48, 95% CI = 1.11, 1.99) and BDCIPP (OR = 1.51; 95% CI = 1.12, 2.03) had a higher odds ratio of MAFLD compared to those in the lowest tertile. WQS regression revealed a detrimental effect of OPEs mixture on MAFLD (OR = 1.40, 95% CI = 1.19, 1.61), with BCIPHIPP (49.3%), and BDCIPP (29.5%) being the major contributors. Sex-specific analyses demonstrated that the positive association of OPEs with MAFLD was only observed in male participants. In conclusion, exposure to the mixture of OPEs was positively correlated with MAFLD and this adverse effect was more evident among men.

BACKGROUND:Previous studies have linked single metal to hemoglobin levels in children and adolescents; however, studies with regards to metal mixtures are still limited. OBJECTIVE:We aimed to investigate the associations of single metal and metal mixtures with hemoglobin levels in children and adolescents. METHODS:We conducted a cross-sectional study of 2064 children and adolescents aged 6 to 19 years in Liuzhou, China in 2018. The concentrations of 15 metals in urine were determined by inductively coupled plasma mass spectrometry. Generalized linear regression and weighted quantile sum (WQS) regression were used to estimate the associations of single metal and metal mixtures with hemoglobin levels, respectively. RESULTS:The multivariable-adjusted β-values for the highest versus the first quartiles of urinary metal concentrations were - 1.57 (95 % confidence interval [CI]: -3.01, -0.13) for chromium, -2.47 (95 % CI: -3.90, -1.05) for nickel and 1.88 (95 % CI: 0.49, 3.28) for copper. In addition, we found a significant negative association between the WQS index and hemoglobin levels (adjusted β = -0.93, 95 % CI: -1.69, -0.19), with nickel contributing the most to the WQS index at 59.0 %. Subgroup analyses showed that exposure to urinary nickel or metal mixtures were associated with decreased hemoglobin levels in adolescents, but not in children (all Pinteration < 0.001). CONCLUSION:Among children and adolescents, urinary chromium and nickel concentrations were associated with decreased hemoglobin levels, while copper showed a positive relationship. Moreover, a negative association was observed between exposure to metal mixtures and hemoglobin levels. These findings need to be further validated in prospective studies.

BACKGROUND:Ankle-brachial index (ABI) is a noninvasive diagnostic method for peripheral arterial disease (PAD) and a predictor of cardiovascular events. OBJECTIVE:The present study aimed to evaluate the association between individual or combined essential metals and ABI, as well as assess the collective impact of essential metals when coupled with healthy lifestyle on ABI. METHODS:A total of 2865 participants were recruited in Wuhan Tongji Hospital between August 2018 and March 2019. Concentrations of essential metals in urine were measured by inductively coupled plasma mass spectrometer. RESULTS:The results of general linear regression models demonstrated that after adjusting for confounding factors, there was a positive association between ABI increase and per unit increase of log 10-transformed, creatinine-corrected urinary Cr (β (95 % CI): 0.010 (0.004, 0.016), PFDR = 0.007), Fe (β (95 % CI): 0.010 (0.003, 0.017), PFDR = 0.018), and Co (β (95 % CI): 0.013 (0.005, 0.021), PFDR = 0.007). The WQS regression revealed a positive relationship between the mixture of essential metals and ABI (β (95 % CI): 0.006 (0.003, 0.010), P < 0.001), with Cr and Co contributing most to the relationship (weighted 45.48 % and 40.14 %, respectively). Compared to individuals with unfavorable lifestyle and the lowest quartile of Cr, Fe and Co, those with favorable lifestyle and the highest quartile of Cr, Fe and Co exhibited the most increase in ABI (β (95 % CI): 0.030 (0.017, 0.044) for Cr, β (95 % CI): 0.027 (0.013, 0.040) for Fe, and β (95 % CI): 0.030 (0.016, 0.044) for Co). CONCLUSION:In summary, our study indicates that adequate essential metal intake together with healthy lifestyle behaviors perform crucial roles in PAD protection.

Recent research has reported positive associations of exposure to polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) with hyperuricemia. However, most of these studies have primarily focused on the individual effects of PCB/OCP exposure. We aimed to explore the associations of both individual and combined PCB/OCP exposure with hyperuricemia and examine whether such associations could be modified by lifestyle factors. The cross-sectional study recruited 2032 adults between March and May 2019 in Wuhan, China. Logistic regression and weighted quantile sum (WQS) regression were applied to explore the relationship of individual and combined PCB/OCP exposure with hyperuricemia, while considering the modified effects of lifestyle factors. Of the 2032 participants, 522 (25.7%) had hyperuricemia. Compared with the non-detected group, the detected groups of PCB153 and PCB180 exhibited a positive association with hyperuricemia, with OR (95% CIs) of 1.52 (1.22, 1.91) and 1.51 (1.20, 1.90), respectively. WQS regression showed that PCB/OCP mixture was positively associated with hyperuricemia (OR: 1.31, 95% CI: 1.08, 1.58). PCB153/PCB180 exposure, combined with an unhealthy lifestyle, has a significant additive effect on hyperuricemia. Overall, PCB/OCP mixture and individual PCB153/PCB180 exposure were positively associated with hyperuricemia. Adherence to a healthy lifestyle may modify the potential negative impact of PCBs/OCPs on hyperuricemia.

ObjectiveTo investigate associations of interpregnancy weight change with preterm birth, low birth weight, macrosomia, small for gestational age (SGA), and large for gestational age (LGA). MethodsThe data on 6 589 pregnant women having two or more singleton live births during 2015 – 2020 and their newborns were extracted from the Maternal and Child Health Information System of Guangdong province. The pregnant women were assigned into four groups according to the changes in their interpregnancy body mass index (BMI) of ＜−1, −1 – ＜1 , 1 – ＜3, and ≥ 3 kg/m2. Logistic regression model was used to assess the associations of interpregnancy BMI change with adverse birth outcomes. ResultsIn all the newborns, the proportion was 5.5% for preterm birth, 4.7% for low birth weight, 2.4% for macrosomia, 11.4% for SGA, and 5.4% for LGA, respectively. The results of logistic regression analysis showed that compared to those with the interpregnancy BMI change of −1 – < 1, the pregnant women having the change of 1 – < 3 have an increased risk of giving a birth to a macrosomia (odds ratio [OR] = 1.66, 95% confidence interval [95% CI]: 1.13 – 2.24); the women with the interpregnancy BMI change of 3 and more have an increased risk of giving a birth to a macrosomia (OR = 2.31, 95% CI: 1.42 – 3.70) and to a LGA infant (OR = 1.87, 95% CI: 1.33 – 2.60); while, each increase of 1 kg/m2 in interpregnancy BMI is associated with a 7% decreased risk of SGA (OR = 0.93, 95% CI: 0.89 – 0.97). No significant association of interpregnancy BMI change with preterm birth or low birth weight was observed (P > 0.05). ConclusionPregnant women′s interpregnancy weight gain is associated with increased risks of macrosomia and LGA of their newborns. The results suggest that body weight control during pregnancy and after delivery need to be promoted among pregnant women.

Imbalance or deficiencies of essential metals can lead to oxidative stress, that can damage mitochondrial DNA (mtDNA) molecule. Knowledge on effects of exposure to essential metals and their mixture remains limited. We aimed to evaluate individual and joint associations of prenatal essential metals with neonatal mtDNA copy number. We recruited 746 mother-newborn pairs from a birth cohort study conducted in Wuhan City, China, and collected trimester-specific urine and cord blood samples. We measured the concentrations of seven urinary essential metals, include zinc (Zn), iron (Fe), selenium (Se), cobalt (Co), manganese (Mn), copper (Cu), and chromium (Cr), using inductively coupled plasma mass spectrometry, and measured cord blood mtDNA copy number using real-time quantitative polymerase chain reaction. We estimated the trimester-specific associations of individual essential metal concentrations with mtDNA copy number using a multiple informant model, and assessed their joint association using weighted quantile sum (WQS) regression. For individual essential metal, a doubling of maternal urinary Zn concentrations during the second trimester was associated with a 7.47% (95% CI: 1.17-14.17%) higher level of neonatal mtDNA copy number. For the essential metal mixture, one-unit increased in the WQS index of the essential metals mixture during the second trimester resulted in a 10.41% (95% CI: 3.04-18.30%) increase in neonatal mtDNA copy number. Our findings suggest that exposure to both Zn and essential metal mixture during the second trimester is associated with a higher neonatal mtDNA copy number. Further research should assess whether mtDNA copy number is associated with child health.

This study aimed to assess the relationships between exposure to individual organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and their mixture and arterial stiffness and explore whether adherence to an ideal cardiovascular health (CVH) could mitigate these associations. The cross-sectional study enrolled 1437 Chinese adults between March and May 2019 in Wuhan, China. OCPs and PCBs concentrations were measured using solid phase extraction coupled with gas chromatography–tandem mass spectrometry. Arterial stiffness was evaluated by brachial–ankle pulse wave velocity (baPWV). CVH was determined by three behavioral and four biological metrics and categorized as ideal, intermediate, and poor CVH. We applied generalized linear model and weighted quantile sum (WQS) regression to evaluate the associations of exposure to individual OCPs or PCBs and their mixture with baPWV, respectively. We found that participants with detectable levels of heptachlor epoxide, PCB-153, and PCB-180 had higher baPWV (β: 34.25, 95

Exposure to environmental pollutants and unhealthy lifestyles are key risk factors for metabolic dysfunction-associated fatty liver disease (MAFLD). While previous studies have suggested links between exposure to organochlorine pesticides (PCBs) and organochlorine pesticides (OCPs) and MAFLD, the results have been inconsistent. Furthermore, the combined effects of PCBs and OCPs on MAFLD and whether lifestyle factors can modify the associations remain unknown. Therefore, this study aimed to investigate the individual and joint effects of PCBs and OCPs on MAFLD and explore the potential modifying role of lifestyle. The study included 1923 participants from Wuhan, China. MAFLD was diagnosed based on ultrasonically diagnosed hepatic steatosis and the presence of overweight/obese, diabetes mellitus, or metabolic dysregulation. Healthy lifestyle score was determined by smoking, alcohol consumption, physical activity, and diet. Logistic regression and weighted quantile sum (WQS) were used to assess associations of individual and mixture of PCBs/OCPs with MAFLD. To explore the potential lifestyle modification, joint associations of PCBs/OCPs and lifestyle on MAFLD were conducted. Single-pollutant analysis showed positive associations of p,p'-DDE, β-HCH, PCB-153, and PCB-180 with MAFLD, with ORs (95% CIs) of 1.18 (1.05, 1.33), 1.57 (1.20, 2.05), 1.45 (1.14, 1.83), and 1.42 (1.12, 1.80), respectively. WQS regression demonstrated a harmful effect of PCBs/OCPs mixture on MAFLD (OR = 1.73, 95% CI = 1.24, 2.43), with β-HCH, p,p'-DDE, and PCB-180 being the major contributors. In the joint association analysis, participants with both high PCBs/OCPs exposure and unhealthy lifestyle have the highest odds of MAFLD. In conclusion, exposure to the mixture of PCBs and OCPs was positively correlated with MAFLD, and adopting a healthy lifestyle can mitigate the adverse impact.

Metallic elements are ubiquitous in the natural environment and always collaborate to affect human health. The relationship of handgrip strength, a marker of functional ability or disability, with metal co-exposure remains vague. In this study, we aimed to investigate the effect of metal co-exposure on sex-specific handgrip strength. A total of 3594 participants (2296 men and 1298 women) aged 21 to 79 years recruited from Tongji Hospital were included in the present study. Urinary concentrations of 21 metals were measured by inductively coupled plasma mass spectrometer (ICP-MS). We used linear regression, restricted cubic spline (RCS) model, and weighted quantile sum (WQS) regression to evaluate the association of single metal as well as metal mixture with handgrip strength. After adjusting for important confounding factors, the results of linear regression showed that vanadium (V), zinc (Zn), arsenic (As), rubidium (Rb), cadmium (Cd), thallium (Tl), and uranium (U) were adversely associated with handgrip strength in men. The results of RCS showed a non-linear association between selenium (Se), silver (Ag), and nickel (Ni) with handgrip strength in women. The results of WQS regression revealed that metal co-exposure was inversely related to handgrip strength for men (β = -0.65, 95

STUDY QUESTION:What are the associations between female-specific reproductive factors and leukocyte telomere length (LTL)?SUMMARY ANSWER:Early menarche, early menopause, short reproductive lifespan, early age at first birth, multiparity, and use of oral contraceptives (OCs) and hormone replacement therapy (HRT) were associated with shorter LTL.WHAT IS KNOWN ALREADY:Reproductive factors have been associated with age-related diseases, but their associations with cellular aging, as indicated by LTL, are unclear.STUDY DESIGN, SIZE, DURATION:This population-based study included 224 965 women aged 40-69 years from the UK Biobank between 2006 and 2010.PARTICIPANTS/MATERIALS, SETTING, METHODS:Women aged 40-69 were included. Female-specific reproductive factors, including age at menarche, age at natural menopause, reproductive lifespan, number of live births, age at first live birth, history of stillbirth, history of miscarriage, and use of OCs and HRT were self-reported. LTL was measured using a validated polymerase chain reaction method. Multiple linear regression and restricted cubic spline models were applied to explore the association between each reproductive factor and LTL.MAIN RESULTS AND THE ROLE OF CHANCE:After adjustment for potential confounders, early menarche (<12 years; percent change, per unit change in LTL Z score: -1.29%, 95% CI: -2.32%, -0.26%), early menopause (<45 years; percent change: -7.18%, 95% CI: -8.87%, -5.45%), short reproductive lifespan (<30 years; percent change: -6.10%, 95% CI: -8.14%, -4.01%), multiparity (percent change: -3.38%, 95% CI: -4.38%, -2.37%), early age at first live birth (<20 years; percent change: -4.46%, 95% CI: -6.00%, -2.90%), and use of OCs (percent change: -1.10%, 95% CI: -2.18%, -0.02%) and HRT (percent change: -3.72%, 95% CI: -4.63%, -2.80%) were all significantly associated with shorter LTL. However, no significant association was found for history of miscarriage and stillbirth. We observed nonlinear relationships of age at menarche, age at natural menopause, reproductive lifespan, and age at first live birth with LTL (Pnonlinear < 0.05).LIMITATIONS, REASONS FOR CAUTION:Considering that the participants were predominantly of European ethnicity, the findings may not be generalizable to women of other ethnic backgrounds.WIDER IMPLICATIONS OF THE FINDINGS:Our findings suggest that early menarche, early menopause, short reproductive lifespan, early age at first birth, multiparity, and use of OCs and HRT were associated with shorter LTL, which has been linked to various chronic diseases. The accelerated shortening of telomeres may potentially contribute to the development of chronic diseases related to reproductive factors.STUDY FUNDING/COMPETING INTEREST(S):This study was funded by the National Natural Science Foundation of China (82003479, 82073660), Hubei Provincial Natural Science Foundation of China (2023AFB663), and the China Postdoctoral Science Foundation (2019M662646, 2020T130220). The authors have no competing interests to disclose.TRIAL REGISTRATION NUMBER:N/A.

Background: Telomere length (TL) at birth is considered a potential biomarker for lifelong health. Although maternal sleep disturbance has been linked to a series of adverse pregnancy outcomes, evidence on the effect of maternal sleep on newborn TL remains scarce. Therefore, we aim to investigate the association of maternal sleep duration and sleep quality with newborn TL. Methods: A total of 742 mother-newborn pairs were recruited from Wuhan Children's Hospital between November 2013 and March 2015. Cord blood TL was measured using real-time quantitative polymerase chain reaction. Maternal sleep duration and quality during late pregnancy were obtained via questionnaires. Multivariate linear regression models were used to estimate the effects of maternal sleep duration and sleep quality on newborn TL. Results: A total of 742 maternal-newborn pairs were included in the analyses. Mothers sleeping =10 hours had a 9.30% (95% CI: 2.09%, 15.99%) shorter newborn TL than those sleeping 7- < 9 hours. However, the association in mothers with short sleep duration (< 7 hours) did not reach statistical significance. Compared to mothers with good sleep quality, those with poor sleep quality had a 9.91% (95% CI: 4.06%, 15.40%) shorter newborn TL. We observed a joint effect of sleep duration and sleep quality on newborn telomere shortening. Women with sleep duration =10 hours and poor sleep quality were most likely to have newborns with short TL (percent change:-19.66%, 95% CI: -28.42, -9.84%). Conclusions: Long sleep duration and poor sleep quality during late pregnancy were associated with shorter newborn TL. (c) 2023 National Sleep Foundation. Published by Elsevier Inc. All rights reserved. All rights reserved.

BACKGROUND:Arterial stiffness is an important indicator of cardiovascular aging. However, studies assessing the association between metal exposure and arterial stiffness are limited.OBJECTIVE:The aim of this study was to investigate the independent and joint associations of metal exposure with arterial stiffness.METHODS:This cross-sectional study recruited 2982 Chinese adults from August 2018 to March 2019 in Wuhan, China. The concentrations of 20 urinary metals were determined using inductively coupled plasma mass spectrometer. Arterial stiffness was assessed by brachial-ankle pulse wave velocity (baPWV). We used generalized linear model (GLM) to estimate the association of single metal exposure with baPWV. We used weighted quantile sum (WQS) regression to estimate the association of metal mixture with baPWV.RESULTS:In GLM regression analysis, each doubling of urinary copper (Cu) and chromium (Cr) concentrations were associated with 6.48 (95 % CI: 2.51-10.45) cm/s and 3.78 (95 % CI: 0.42-7.14) cm/s increase in baPWV, respectively. In WQS regression analysis, each unit increase in WQS index of the metal mixture was associated with a 9.10 (95 % CI: 2.39-15.82) cm/s increase in baPWV. Cu, Zn, and Cr were the dominant urinary metals associated with baPWV.CONCLUSION:Metal exposure, both individually and in mixture, was associated with an increased risk of arterial stiffness. Our findings may provide a target for preventative strategies against cardiovascular aging.