Objective
We conducted a Mendelian randomization (MR) study to disentangle causal associations between women's reproductive behaviors and ischemic stroke (IS) and investigate the roles of two ...modifiable risk factors (body mass index (BMI) and educational attainment (EA)) in these associations.
Methods
Using summary‐level data from large‐scale genome‐wide association studies, we performed univariable MR to examine whether there is genetic evidence that women's reproductive traits are causally associated with IS and its subtypes. Multivariable MR and MR mediation analysis were used to investigate whether BMI and EA are common mechanisms or mediators for these associations. A set of sensitivity analyses were conducted to test valid MR assumptions.
Results
We observed consistent and statistically significant associations across female and sex‐combined analyses for earlier age at first birth (AFB) and age at first sexual intercourse (AFS) with a higher risk of IS and large‐artery atherosclerotic stroke (LAS) risk in the primary analysis. The odds ratios of IS per 1 SD increase in genetically predicted early AFB and AFS were 0.93 (95% CI, 0.86–0.99; p = 0.046) and 0.83 (95% CI, 0.70–0.97, p = 0.020), respectively. Further analyses indicated that BMI played a shared role in AFS and IS/LAS while EA played a shared role in AFS/AFB and IS/LAS as well as a mediator in the path from AFS to IS/LAS.
Interpretation
These findings may inform prevention strategies and interventions directed toward relative women's reproductive behaviors and IS. Future studies are warranted to explore other factors related to EA which are responsible for these causalities.
Abstract
Observational studies suggest certain sleep traits are associated with telomere length, but the causal nature of these associations is unclear. The study aimed to determine the causal ...associations between 11 sleep-related traits and leukocyte telomere length (LTL) through two-sample Mendelian randomization and colocalization analyses using the summary statistics from large-scale genome-wide association studies. Univariable Mendelian randomization indicates that genetically determined short sleep is associated with decreased LTL, while morning chronotype is associated with increased LTL. Multivariable Mendelian randomization further supports the findings and colocalization analysis identifies shared common genetic variants for these two associations. No genetic evidence is observed for associations between other sleep-related traits and LTL. Sensitivity MR methods, reverse MR and re-running MR after removing potential pleiotropic genetic variants enhance the robustness of the results. These findings indicate that prioritizing morning chronotype and avoiding short sleep is beneficial for attenuating telomere attrition. Consequently, addressing sleep duration and chronotype could serve as practical intervention strategies.
With the development of integrated energy system, energy flow analysis of coupling energy network has attracted much attention. In this study, based on the unified energy path theory, energy flow ...analysis of electricity-heating coupled energy system is implemented considering different time characteristic of each system. Considering the instantaneous change process of heat transfer in the heating system, the dynamic model of heat network is constructed based on unified energy path theory. On this basis, the dynamic models of electric and heating systems are coupled, and the dynamic energy flow calculation method of the coupling system is proposed. Through a case study, the feasibility of the proposed model and calculation method are verified. In addition, the effect of heat source on the dynamic process of heat transfer in the heating system is analyzed.
Considering the volatility and randomness of renewable energy, the integrated demand response (IDR) has proved to be an efficient way to solve the imbalance problem between the supply and demand ...sides. To manage the flexible loads of customers, as an intermediate participant, the residential load aggregator (RLA) is introduced, which can provide a motivational measure to attract customers to participate in electric and heating IDR. In this study, an incentive-based reward mechanism (RM) is proposed for a RLA based on classified residential customers, to obtain the best bidding contracts in the load market. A novel multi-objective optimization model is developed and calculated by an NSGA-II artificial algorithm maximizing profits of the RLA and customers simultaneously. The customers’ profit is described as the monetization of dissatisfaction degree considering both psychology and comfort aspects. Furthermore, to demonstrate the practicality and advantage of the RM, the price-based IDR mechanism is also included in the numerical study for comparison. According to the simulation results, although both RM-based and price-based responses have their own advantages and disadvantages on various performances, the RM performs better since it can reduce more energy demand and save more costs for end-users.
A co-benefits assessment index system is developed for the introduction of a regional integrated energy system (RIES). Following which, by analyzing the interest demands of each stakeholder and ...determining the beneficiaries of each unit benefit, the initial benefit distribution model based on attribution relationship is established. According to the networked relationship of stakeholders, a fair and reasonable cost sharing mechanism for RIES is established. On this basis, the benefit–cost (B/C) analysis is carried out from various stakeholders to evaluate the commercial feasibility. According to the simulation results of a numerical study, the project as a whole and all stakeholders have B/C values greater than 1 to coordinate and balance related issues such as system income distribution according to the designed benefit distribution mechanism. In this way, the win-win situation of overall interests and individual interests can be realized.
Acrylamide (AA) and ochratoxin A (OTA) are contaminants that co-exist in the same foods, and may create a serious threat to human health. However, the combined effects of AA and OTA on intestinal ...epithelial cells remain unclear. The purpose of this research was to investigate the effects of AA and OTA individually and collectively on Caco-2 cells. The results showed that AA and OTA significantly inhibited Caco-2 cell viability in a concentration- and time-dependent manner, decreased transepithelial electrical resistance (TEER) values, and increased the lucifer yellow (LY) permeabilization, lactate dehydrogenase (LDH) release and reactive oxygen species (ROS) levels. In addition, the levels of IL-1β, IL-6, and TNF-α increased, while the levels of IL-10 decreased after AA and OTA treatment. Western blot analysis revealed that AA and OTA damaged the intestinal barrier by reducing the expression of the tight junction (TJ) protein. The collective effects of AA and OTA exhibited enhanced toxicity compared to either single compound and, for most of the intestinal barrier function indicators, AA and OTA combined exposure tended to produce synergistic toxicity to Caco-2 cells. Overall, this research suggests the possibility of toxic reactions arising from the interaction of toxic substances present in foodstuffs with those produced during processing.
•Visit-to-visit blood pressure variability in the second/third trimester or during the whole pregnancy were independently associated with gestational hypertension (GH) and pre-eclampsia ...(PE).•Visit-to-visit blood pressure variability increased from the second to the third trimester, and the increasement in hypertensive participants was enlarged.•Adding coefficient variance of systolic blood pressure to conventional risk model could facilitate identification for pregnant woman at high risk of GH or PE.
Visit-to-visit blood pressure variability (VVV) was an independent risk factor for cardiovascular events. In pregnant women whose hemodynamic changes are unique, the role of VVV in hypertensive disorders is still obscure. Therefore, we aimed to investigate the association of VVV with gestational hypertension (GH) and pre-eclampsia (PE).
14,702 pregnant women were recruited at around 13 weeks of their gestation. VVV during the second, third trimester and the whole pregnancy, were estimated as standard deviation (SD) or coefficient of variation (CV) of systolic blood pressure (SBP) or diastolic blood pressure (DBP). The associations between VVV, GH and PE were assessed by multivariate logistic regression models.
878 and 131 women developed GH and PE, respectively. VVV was significantly higher in GH and PE subjects than normotensive controls, regardless of whichever metric was calculated. In maximally adjusted models, odds ratio (95% confidence interval) of SBP-CV during the whole pregnancy was 1.62 (1.56–1.68) for GH, 1.14 (1.06–1.21) for PE, and 1.51 (1.47–1.56) for either GH or PE. The cooperation of SBP-CV to other risk factors could help in discriminating pregnant women at high risk of GH and PE.
VVV during pregnancy, especially SBP-CV, was independently associated with GH and PE. These results suggested that VVV could provide additional information to identify pregnant women at high risk of GH or PE. Further studies exploring prospective association between VVV, GH and PE are warranted.
Among the vertebrate lineages with different hearing frequency ranges, humans lie between the low-frequency hearing (1 kHz) of fish and amphibians and the high-frequency hearing (100 kHz) of bats and ...dolphins. Little is known about the mechanism underlying such a striking difference in the limits of hearing frequency. Prestin, responsible for cochlear amplification and frequency selectivity in mammals, seems to be the only candidate to date. Mammalian prestin is densely expressed in the lateral plasma membrane of the outer hair cells (OHCs) and functions as a voltage-dependent motor protein. To explore the molecular basis for the contribution of prestin in hearing frequency detection, we collected audiogram data from humans, dogs, gerbils, bats, and dolphins because their average hearing frequency rises in steps. We generated stable cell lines transfected with human, dog, gerbil, bat, and dolphin prestins (hPres, dPres, gPres, bPres, and nPres, respectively). The non-linear capacitance (NLC) of different prestins was measured using a whole-cell patch clamp. We found that the
Q
max
/
C
lin
of bPres and nPres was significantly higher than that of humans. The
V
1
/
2
of hPres was more hyperpolarized than that of nPres. The
z
values of hPres and bPres were higher than that of nPres. We further analyzed the relationship between the high-frequency hearing limit (
F
max
) and the functional parameters (
V
1
/
2
,
z
, and
Q
max
/
C
lin
) of NLC among five prestins. Interestingly, no significant correlation was found between the functional parameters and
F
max
. Additionally, a comparative study showed that the amino acid sequences and tertiary structures of five prestins were quite similar. There might be a common fundamental mechanism driving the function of prestins. These findings call for a reconsideration of the leading role of prestin in hearing frequency perception. Other intriguing kinetics underlying the hearing frequency response of auditory organs might exist.
Observational studies have suggested a potential non-linear association between sleep duration and hyperuricemia. However, the causal nature and sex-specific differences are poorly understood. We ...aimed to determine the shape of sex-specific causal associations between sleep duration and hyperuricemia in the UK Biobank.
Logistic regression was used to investigate the observational association between self-reported sleep duration and hyperuricemia among 387,980 white British participants (mean age: 56.9 years and 46.0% males). Linear and non-linear Mendelian Randomization (MR) analyses were performed to assess the causal association between continuous sleep duration and hyperuricemia. The causal effects of genetically predicted short (<7 h) and long (>8 h) sleep durations on hyperuricemia were further estimated, respectively.
Traditional observational analysis suggested U- and J-shaped associations between sleep duration and hyperuricemia in females and males, respectively. Linear MR did not support the causal effect of sleep duration on hyperuricemia. Non-linear MR demonstrated an approximately U-shaped causal association between continuous sleep duration and hyperuricemia in overall participants and females, but not in males. Genetically predicted short sleep duration was significantly associated with hyperuricemia in females (OR 95% CI: 1.21 1.08-1.36;
= 0.001), but not in males (1.08 0.98-1.18;
= 0.137). By contrast, genetically predicted long sleep duration was not significantly associated with the risk of hyperuricemia in either females or males.
Genetically predicted short sleep duration is a potential causal risk factor for hyperuricemia for females but has little effect on males. Long sleep duration does not appear to be causally associated with hyperuricemia.
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