Long-term nanoplastics exposure contributes to impaired steroidogenesis by disrupting the hypothalamic-testis axis: Evidence from integrated transcriptome and metabolome analysis.

Cumulative evidence suggested that nanoplastics (NPs) cause male toxicity, but the mechanisms of which are still misty. Steroidogenesis is a key biological event that responsible for maintaining reproductive health. However, whether dysregulated steroidogenesis is involved in NPs-induced impaired male reproductive function and the underlying mechanism remains unclear. In our study, Balb/c mice were continuously exposed to pristine-NPs or NH2-NPs for 12 weeks, spanning the puberty and adult stage. Upon the long-term NPs treatment, the hypothalamus and testis were subjected to transcriptome and metabolome analysis. And the results demonstrated that both primitive-NPs and NH2-NPs resulted in impaired spermatogenesis and steroidogenesis, as evidenced by a significant reduction in sperm quality, testosterone, FSH, and LH. The expression of genes involved in hypothalamic-pituitary-testis (HPT) axis, such as Kiss-1 and Cyp17a1 that encoded the key steroid hormone synthetase, was also diminished. Furthermore, the phosphatidylcholine and pantothenic acid that mainly enriched in glycerophospholipid metabolism were significantly reduced in the testis. Comprehensive analysis of the transcriptome and metabolome indicated that down-regulated Cyp17a1 was associated with decreased metabolites phosphatidylcholine and pantothenic acid. Overall, we speculate that the disturbed HPT axis induced by long-term NPs contributes to disordered glycerophospholipid metabolism and subsequently impaired steroidogenesis. Our findings deepen the understanding of the action of the mechanism responsible for NPs-induced male reproductive toxicology.

The multimorbidity association of metabolic syndrome and depression on type 2 diabetes: a general population cohort study in Southwest China.

Background: Metabolic syndrome(MetS) and depression are independently associated with type 2 diabetes (T2DM) risk. However, little is known about the combined effect of MetS and depression on the risk of T2DM. The present study aims to prospectively explore the impact of MetS and depression on T2DM susceptibility among the Chinese general population. Methods: 6489 general population without T2DM adults in Southwest China were recruited from 2010 to 2012. Depression and MetS were prospectively assessed using a 9-item Patient Health Questionnaire(PHQ-9) and Guideline for the prevention and treatment of type 2 diabetes mellitus in China (2020 edition) (CDS2020) during 2016-2020, respectively. Modified Poisson regression models were conducted to estimate relative risk(RR) and 95% confidence intervals (95%CI) for independent and combined associations of MetS and depression with an incidence of T2DM. Results: During a median follow-up of 6.6 years, 678 cases of T2DM were documented. Individuals with MetS were 1.33 times more likely to develop T2DM than those without MetS. The corresponding RR(95%CI) for depression with no depression was 1.45(1.22-1.72). Notably, compared with no MetS or depression, the multivariate-adjusted RR for a combined effect of MetS and depression on the risk of T2DM was 2.11(1.39-3.22). Moreover, an increased risk of T2DM was more apparent in those ≥ 60 years, males, and overweight. Conclusions: Individuals with multimorbidity of MetS and depression are at a higher risk of T2DM compared with those with no MetS or depression.

Autophagy aggravates multi-walled carbon nanotube-induced ferroptosis by suppressing PGC-1 dependent-mitochondrial biogenesis in lung epithelial cells.

Multi-walled carbon nanotube (MWCNT) induced respiratory toxicity has become a growing concern, with ferroptosis emerging as a novel mechanism implicated in various respiratory diseases. However, whether ferroptosis is involved in MWCNT-elicited lung injury and the underlying molecular mechanisms warrant further exploration. In this study, we found that MWCNT-induced ferroptosis is autophagy-dependent, contributing to its cellular toxicity. Inhibiting of autophagy by pharmacological inhibitors 3-MA or ATG5 gene knockdown significantly attenuated MWCNT-induced ferroptosis, concomitant with rescued mitochondrial biogenesis. Rapamycin, the autophagy agonist, exacerbated the mitochondrial damage and MWCNT-induced ferroptosis. Moreover, lentivirus-mediated overexpression of PGC-1α inhibited ferroptosis, while inhibition of PGC-1α aggravated ferroptosis. In summary, our study unveils ferroptosis as a novel mechanism underlying MWCNT-induced respiratory toxicity, with autophagy promoting MWCNT-induced ferroptosis by hindering PGC-1α-dependent mitochondrial biogenesis.

Association of remnant cholesterol with CVD incidence: a general population cohort study in Southwest China.

Background: Emerging evidence has indicated that remnant cholesterol (RC) could predict cardiovascular disease (CVD) incidence. Nevertheless, the relationship between RC and CVD risk, especially within the general Chinese population, remains scarce. Objective: The present research aimed to assess whether RC concentrations and CVD outcomes in general Chinese adults are related. Methods: The Cox proportional hazard model was established to explore the relationship between RC and the outcomes of CVD and CVD subgroups. A restricted cubic spline (RCS) was utilized to investigate the dose-response connection between RC and the risk of CVD outcomes, and the ROC curve was used to calculate the corresponding cutoff values. Moreover, stratified analysis was conducted to investigate the potential effect modification in the association between RC and CVD outcomes. Results: Significant positive associations were found between elevated categorical RC and increased risk of CVD (HR Q4, 1.80; 95% CI 1.15-2.79; P-value = 0.008), atherosclerotic cardiovascular disease (HR Q4, 2.00; 95% CI 1.22-3.27; P-value = 0.007), stroke (HR Q4, 1.66; 95% CI 1.02-2.69; P-value = 0.040), and ischemic stroke (HR Q4, 1.87, 95% CI 1.08-3.25; P-value = 0.034), respectively. Our study suggested that the incidence of CVD outcomes increased when RC levels were above 0.75 mmol/L. Importantly, the CVD risks related to RC were more likely to be those found in subjects aged above 60 years, women, subjects with BMI <24 kg/m2, and subjects with hypertension and unhealthy diet patterns. Conclusions: Aberrant high level of RC is associated with elevated CVD risk, independent of low-density lipoprotein cholesterol (LDL-C). Our data reveal urgent primary prevention for subjects with high RC levels to a low incidence of CVD, especially for the elderly, women, and those with hypertension and unhealthy diet patterns.

Co-Exposure of Polycyclic Aromatic Hydrocarbons and Phthalates with Blood Cell-Based Inflammation in Early Pregnant Women.

Cumulative evidence has demonstrated that exposure to polycyclic aromatic hydrocarbons (PAHs) or phthalates (PAEs) contributes to a variety of adverse health effects. However, the association of PAHs and PAEs co-exposure with blood cell-based inflammatory indicators during early pregnancy is still unclear. We aimed to investigate the single and mixed associations of exposure to PAHs and PAEs with blood cell-based inflammatory indicators among early pregnant women. A total of 318 early pregnant women were included in this study. General linear regressions were used to estimate the relationships of individual OH-PAHs and mPAEs with blood cell-based inflammatory indicators. The key pollutants were selected by an adapted least absolute shrinkage and selection operator (LASSO) penalized regression model and wasemployed to build the Bayesian kernel machine regression (BKMR) and quantile g-computation (Q-g) models, which can assess the joint association of OH-PAHs and mPAEs with blood cell-based inflammatory indicators. General linear regression indicated that each 1% increase in MOP was associated with a 4.92% (95% CI: 2.12%, 7.68%), 3.25% (95% CI: 0.50%, 6.18%), 5.87% (95% CI: 2.22%, 9.64%), and 6.50% (95% CI: 3.46%, 9.64%) increase in WBC, lymphocytes, neutrophils, and monocytes, respectively. BKMR and Q-g analysis showed that the mixture of OH-PAHs and mPAEs was linked with increased levels of white blood cells (WBC), neutrophils, monocytes, and lymphocytes, and MOP was identified as the dominant contributor. OH-PAHs and mPAEs co-exposure in early pregnancy was associated with elevated blood cell-based inflammatory indicators reactions. More attention should be paid to the inflammation induced by environmental pollution for perinatal women, especially early pregnant women.

Single and Joint Associations of Polycyclic Aromatic Hydrocarbon Exposure with Liver Function during Early Pregnancy.

The individual and combined associations of polycyclic aromatic hydrocarbons (PAHs) metabolites on liver function during pregnancy are still lacking. We aimed to explore the connection between urinary PAH metabolites and liver function in early pregnant women in southwest China based on the Zunyi birth cohort. Ten urinary PAH metabolites and five liver function parameters during early pregnancy were measured. The associations of single PAHs with parameters of liver function were assessed using multiple linear regression. A Bayesian kernel machine regression (BKMR) model was used to evaluate the joint associations of the PAH mixture with outcomes. We found that each 1% increment of urinary 2-hydroxyphenanthrene (2-OH-PHE) was associated with 3.36% (95% CI: 0.40%, 6.40%) higher alanine aminotransferase (ALT) and 2.22% (95% CI: 0.80%, 3.67%) higher aspartate aminotransferase (AST). Each 1% increment in 1-hydroxy-phenanthrene (1-OH-PHE) was significantly associated with 7.04% (95% CI: 1.61%, 12.75%) increased total bile acid (TBA). Additionally, there was a significant positive linear trend between 2-OH-PHE and AST and 1-OH-PHE and TBA. BKMR also showed a significant positive association of PAH mixture with AST. Our results indicate that PAH metabolites were associated with increased parameters of liver function among early pregnant women. Early pregnant women should pay more attention to the adverse relationships between PAHs and liver function parameters to prevent environment-related adverse perinatal outcomes.

Gut microbiota combined with metabolome dissects long-term nanoplastics exposure-induced disturbed spermatogenesis.

As the concerned emerging pollutants, several lines of evidence have indicated that nanoplastics (NPs) lead to reproductive toxicity. However, the biological mechanism underlying NPs disturbed spermatogenesis remains largely unknown. Therefore, we aimed to reveal the potential mechanism of impaired spermatogenesis caused by long-term NPs exposure from the perspective of integrated metabolome and microbiome analysis. After 12 weeks of gavage of polystyrene nanoplastics (PS-NPs) and animo-modified polystyrene nanoplastics (Amino-NPs), a well-designed two-exposure stages experimental condition. We found that NPs exposure induced apparent abnormal spermatogenesis, which appeared more severe in the Amino-NPs group. Mechanistically, 14 floras associated with glucose and lipid metabolism were significantly altered, as evidenced by 16 S rRNA sequencing. Testicular metabolome revealed that the Top 50 changed metabolites were also enriched in lipid metabolism. Subsequently, the combined gut microbiome and metabolome analysis uncovered the strong correlations between Klebsiella, Blautia, Parabacteroides, and lipid metabolites (e.g., PC, LysoPC and GPCho). We speculate that the dysbiosis of gut microbiota-related disturbed lipid metabolism may be responsible for long-term NPs-induced damaged spermatogenesis, which provides new insights into NPs-induced dysregulated spermatogenesis.

Association between depression and risk of type 2 diabetes and its sociodemographic factors modifications: A prospective cohort study in southwest China.

BACKGROUND: Depression may be associated with the risk of developing type 2 diabetes. The goal of this study was to explore the association of severe of depression with the risk of type 2 diabetes in adults in Guizhou, China. METHODS: A 10-year prospective cohort study of 7158 nondiabetes adults aged 18 years or older was conducted in Guizhou, southwest China from 2010 to 2020. The Patient Health Questionnaire-9 (PHQ-9) was used to measure the prevalence of depression. Cox proportional hazard models were used to estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) of depression and incident type 2 diabetes. A quantile regression (QR) analytical approach were applied to evaluate the associations of PHQ-9 score with plasma glucose values. RESULTS: A total of 739 type 2 diabetes cases were identified during a median follow-up of 6.59 years. The HR (95% CI) per 1-SD increase for baseline PHQ-9 score was 1.051 (1.021, 1.082) after multivariable adjustment. Compared with participants without depression, those with mild or more advanced depression had a higher risk of incident type 2 diabetes (HR:1.440 [95% CI, 1.095, 1.894]). Associations between depression with type 2 diabetes were suggested to be even stronger among women or participants aged ≥45 years (p < .05). There are significant positive associations of PHQ-9 score with 2-h oral glucose tolerance test blood glucose levels. CONCLUSION: Depression significantly increased the risk of incident type 2 diabetes, especially in women, participants aged ≥45 years, Han ethnicity, and urban residents. These findings highlighted the importance and urgency of depression health care.

Regular consumption of pickled vegetables and fermented bean curd reduces the risk of diabetes: a prospective cohort study.

Objective: The global incidence of diabetes is rising, in part due to the widespread adoption of poor dietary habits. Fermented vegetables have numerous health benefits and are generally affordable. Here, we examined whether regular consumption of pickled vegetables or fermented bean curd reduces the risk of diabetes. Methods: A total of 9,280 adults (≥18 years of age) were recruited via multi-stage sampling from 48 townships in China between 2010 and 2012 for this 10-year prospective study. In addition to demographic information, monthly consumption levels of pickled vegetables and fermented bean curd were recorded. Participants were then monitored for diabetes onset. After the final follow-up, logistic regression analyses with multiple covariant corrections were conducted to estimate the changes in diabetes risk associated with consumption of pickled vegetables and fermented bean curd compared to non-consumption. Results: A total of 6,640 subjects without diabetes at the start of the study were followed up for a median period of 6.49 years, among whom 714 were diagnosed with diabetes during the study. According to a regression model with multivariable adjustment, diabetes risk was significantly reduced by consumption of 0-0.5 kg/month of pickled vegetables (OR = 0.77, 95% CI: 0.63, 0.94) and further reduced by consumption of >0.5 kg/month of pickled vegetables (OR = 0.37, 95% CI: 0.23, 0.60) compared to no consumption (both P-trend < 0.001). Consumption of fermented bean curd also reduced diabetes risk (OR = 0.68, 95% CI: 0.55, 0.84). Conclusion: Regular consumption of pickled vegetables and/or fermented bean curd can reduce the long-term risk of diabetes.

Single and joint associations of exposure to polycyclic aromatic hydrocarbons with blood coagulation function during pregnancy: A cross-sectional study.

Association linking polycyclic aromatic hydrocarbons (PAHs) to blood coagulation function during pregnancy remains absent. Hence, we conducted a cross-sectional study including 679 late pregnant women (27.2 ± 5.1 years old) drawn from Zunyi birth cohort, Southwest China. During late pregnancy, ten urinary PAHs metabolites and four clinical blood coagulation parameters were measured, including activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), and fibrinogen (FIB). Multiple linear regression, Restricted cubic spline (RCS) regression, Bayesian kernel machine regression (BKMR), and quantile g-computation (Q-g) regression were used to investigate their single, nonlinear, and mixed associations. Each 2.7-fold increment in 2-hydroxyfluorene (2-OHFlu), 9-hydroxyfluorene (9-OHFlu), 1-hydroxyphenanthrene (1-OHPhe), 2-hydroxyphenanthrene (2-OHPhe), and 3-hydroxyphenanthrene (3-OHPhe) were associated with 0.287 s, 0.190 s, 0.487 s, and 0.396 s shorter APTT, respectively; each 2.7-fold increment in 2-OHPhe was associated with a 0.047 s longer PT; each 2.7-fold increment in 9-hydroxyphenanthrene (9-OHPhe) and 1-hydroxypyrene (1-OHPyr) were associated with 0.087 s and 0.031 s shorter TT, respectively; and each 2.7-fold increment in 1-hydroxynaphthalene (1-OHNap) was associated with 0.032 g/L higher FIB level. The nonlinear association of 2-OHPhe with APTT and 1-OHNap with FIB were also observed. Furthermore, the shortened APTT and TT associated with PAHs mixture were indicated by BKMR and Q-g model. BKMR also revealed a nonlinear association of 2-OHPhe with PT and an interaction effect of 2-OHPhe and 3-OHPhe on APTT. Our results indicate that urinary PAHs was associated with shortened coagulation time and increased FIB. Therefore, more attention should be paid for late pregnant women to prevent PAHs-associated risk of thrombosis. Future perspective studies to confirm our findings and explore the underlying biological mechanism are warranted.

Transport of microplastics in the body and interaction with biological barriers, and controlling of microplastics pollution.

Microplastics (MPs) are one novel environmental pollutant sized < 5 mm that is ubiquitously present in numerous environmental media and particularly susceptible to interact with various toxic chemicals. Importantly, MPs can enter the food chain, and are bio-enriched and bio-accumulated with trophic levels, eventually endangering ecosystems and human health. However, there need to be more understanding regarding the bio-interaction of MPs with the host, particularly for biological barriers. This review aimed to summarize the latest findings regarding the main exposure routes of MPs that generated health burdens on humans. Furthermore, their interactions with biological barriers that generate adverse health effects and the underlying mechanisms were also reviewed. Additionally, we provided a comprehensive overview of recent advances regarding the removing and controlling of MPs. Finally, we discussed the future directions for MPs hazard prevention to provide helpful information for regulating decision-making and guiding safer plastics applications.

Long-term release kinetic characteristics of microplastic from commonly used masks into water under simulated natural environments.

Masks-related microplastic pollution poses a new threat to the environment and human health that has gained increasing concern. However, the long-term release kinetics of microplastic from masks in aquatic environments have yet to studied, which hampers its risk assessment. Four types of masks, namely cotton mask, fashion mask, N95 mask, and disposable surgical mask were exposed to systematically simulated natural water environments to determine the time-dependent microplastic release characteristics at 3, 6, 9, and 12 months, respectively. In addition, the structure changes of employed masks were examined by scanning electron microscopy. Moreover, Fourier transform infrared spectroscopy was applied to analyze the chemical composition and groups of released microplastic fibers. Our results showed that the simulated natural water environment could degrade four types of masks and continuously produce microplastic fibers/fragments in a time-dependent manner. The dominant size of released particles/fibers was below 20 µm across four types of face masks. The physical structure of all four masks was damaged to varying degrees concomitant with photo-oxidation reaction. Collectively, we characterized the long-term release kinetics of microplastic from four types of commonly used masks under a well-mimic real word water environment. Our findings suggest that urgent action must be taken to properly manage disposable masks and ultimately limit the health threats associated with discarded masks.

Alternative splicing of PSMD13 mediated by genetic variants is significantly associated with endometrial cancer risk.

OBJECTIVE: Accumulating evidence has shown that aberrant alternative splicing events are closely associated with the onset and development of cancer. However, whether genetic variants-associated alternative splicing is linked to risk of endometrial cancer remains largely uncertain. METHODS: We identified single nucleotide polymorphisms (SNPs) locates in the splicing number trait locus (sQTL) of endometrial cancer using the CancerSplicing QTL database. In parallel with bioinformatics analysis, we conducted a case-control study comprising 2,000 cases and 2,013 controls to assess the association between identified SNP which possesses mRNA splicing function and endometrial cancer susceptibility. Furthermore, we used the Kaplan-Meier Plotter, The Human Protein Atlas, SPNR, and Spliceman2 databases for sQTL and differential gene expression analyses to identify the genetic variant which most potentially influence the risk of endometrial cancer through alternative splicing to reveal the potential mechanism by which candidate SNPs regulate the risk of endometrial cancer. RESULTS: The results indicated that SNP rs7128029 A

Risk assessment and environmental determinants of urinary phthalate metabolites in pregnant women in Southwest China.

Pregnant women are widely exposed to phthalic acid esters (PAEs) that are commonly used in most aspects of modern life. However, few studies have examined the cumulative exposure of pregnant women to a variety of PAEs derived from the living environmental conditions in China. Therefore, this study aimed to determine the urinary concentrations of nine PAE metabolites in pregnant women, examine the relationship between urinary concentrations and residential characteristics, and conduct a risk assessment analysis. We included 1,888 women who were in their third trimester of pregnancy, and we determined their urinary concentrations of nine PAE metabolites using high-performance gas chromatography-mass spectrometry. The risk assessment of exposure to PAEs was calculated based on the estimated daily intake. A linear regression model was used to analyze the relationship between creatinine-adjusted PAE metabolite concentrations and residential characteristics. The detection rate of five PAE metabolites in the study population was > 90%. Among the PAE metabolites adjusted by creatinine, the urinary metabolite concentration of monobutyl phthalate was found to be the highest. Residential factors, such as housing type, proximity to streets, recent decorations, lack of ventilation in the kitchen, less than equal to three rooms, and the use of coal/kerosene/wood/wheat straw fuels, were all significantly associated with high PAE metabolite concentrations. Due to PAE exposure, ~ 42% (n = 793) of the participants faced potential health risks, particularly attributed to dibutyl phthalate, diisobutyl phthalate, and di(2-ethyl)hexyl phthalate exposure. Living in buildings and using coal/kerosene/wood/wheat straw as domestic fuel can further increase the risks.

Effects of exposure to phthalate during early pregnancy on gestational diabetes mellitus: a nested case-control study with propensity score matching.

Owing to the complexity of phthalates (PAEs) components and the diversity of their sources, the health hazards of their metabolites to pregnant women remain unclear. This study aimed to explore the relationship between exposure to PAEs during early pregnancy and gestational diabetes mellitus (GDM) in rural pregnant women. We assessed pregnant women with (n = 338) or without (n = 3082) GDM from the ongoing Zunyi Birth Cohort. Participants' urine samples were collected to measure the levels of 10 metabolites of PAEs. GDM was diagnosed using the 75-g oral glucose tolerance test at 24-28 weeks of gestation. We adopted propensity score matching based on GDM-related factors and pregnant women's backgrounds to establish two groups of 338 patients: those with or without GDM. In the cohort, we included 5734 pregnant women; 519 of them developed GDM, yielding a GDM incidence rate of 9.05%. Urinary concentrations of monooctyl phthalate (MOP), mono-benzyl phthalate (MBzP), mono(2-ethyl-5-oxyhexyl) phthalate (MEOHP), and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) during early pregnancy were significantly associated with GDM (P < 0.05). Logistic regression models revealed that MEOHP in the urine was positively associated with GDM (odds ratio [OR] = 1.55; 95% confidence interval [CI]: 1.00-2.39). Furthermore, restricted cubic spline models revealed that urine MEOHP concentrations greater than 15.6 µg/L were positively associated with GDM, and approximately 23.5% pregnant women had urine MEOHP concentrations greater than 15.6 µg/L. Thus, approximately 23.5% of pregnant women were at the risk of developing GDM due to MEOHP, which suggested that pregnant women should reduce the use of packaged food and cosmetics to reduce the risk of GDM. However, further molecular biology experiments are required to confirm these findings and to elucidate the underlying mechanisms.

Maternal urine phthalate metabolite exposure and miscarriage risk: a nested case-control study of the Zunyi Birth Cohort.

Phthalates (PAEs) are widespread persistent organic pollutants and endocrine disruptors. However, the associations between PAE exposure and the risk of miscarriage in humans are unclear, and an insufficient number of studies have evaluated the possible threshold or dose-dependent effects of first trimester PAE exposure on miscarriage risk. Our research measured the levels of mono-methyl phthalate (MMP), mono-ethyl phthalate, mono-isobutyl phthalate, MiBP mono-butyl phthalate (MBP), mono-octyl phthalate, mono-benzyl phthalate, mono(2-ethylhexyl) phthalate, mono(2-ethyl-5-oxohexyl) phthalate, and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) in maternal urine collected in early gestation between 150 pregnancies ending in miscarriage and 150 pregnancies with live birth. We also estimated the odds ratios (ORs) and 95% confidence intervals (CIs) for miscarriage and each PAE as a continuous variable or quartile. A restrictive cubic splines was used to assess dose-dependent effects after controlling for maternal characteristics (e.g., age, educational level). we identified monotonically increasing dose-dependent effects of MEHHP and MMP on the risk of miscarriage. The largest effect estimates were approximately threefold higher for the highest MBP (OR = 2.57; 95% CI = 1.32-5.01) or MMP quartile (OR = 3.57; 95% CI = 1.82-7.00) and two-fold higher for the highest MEHHP quartile (OR = 2.12; 95% CI = 1.10-4.11). Our research preliminarily obtained possible thresholds of MBP, MEHHP, and MMP which were 18.07, 2.38, and 0.80 µg/g Cr for the risk of miscarriage, respectively. First-trimester exposure to MBP, MEHHP, and MMP exceeding certain thresholds increases the risk of miscarriage.

Organochlorine pesticide exposures, metabolic enzyme genetic polymorphisms and semen quality parameters among men attending an infertility clinic.

The associations of organochlorine pesticides (OCPs) with semen quality from human studies are conflicting, and also it is largely unknown whether the associations are modified by genetic polymorphisms. We aimed to evaluate the associations between serum concentrations of 18 OCPs and semen quality among 387 Chinese men, and further to examine the modifying effects by genetic polymorphisms in cytochrome P450 (CYP2E1) and glutathione S-transferase (GSTT1). Multivariable linear regressions were used to evaluate the relationships between serum OCP concentrations and semen quality, and the role of CYP2E1 and GSTT1 polymorphisms in modifying the associations were assessed. Multiple testing was adjusted using the false discovery rate (FDR). We observed that men with detectable concentrations of serum ɤ-HCH had a decrease in sperm motility of 7.07% (95% CI: -10.9%, -3.24%) compared to those with undetectable concentrations (FDR-P value = 0.02). Men with TT of CYP2E1 rs 915906 genotypes had higher median concentrations of serum dieldrin compared with those with CT/CC of CYP2E1 rs 915906 genotypes. There were interactions between CYP2E1 and GSTT1 polymorphisms and certain OCPs namely ɤ-HCH, δ-HCH, dieldrin, endosulfan I, and endrin aldehyde on semen quality. For example, elevated dieldrin levels in relation to decreased sperm concentration, sperm count, and sperm motility were only observed among men with CC of CYP2E1 rs2031920 genotypes (all Pinteraction < 0.05). However, these interactions were not statistically significant after the FDR adjustment. Our results suggested that CYP2E1 and GSTT1 polymorphisms may modify the effects of OCP exposures on semen quality. Due to the relatively small size samples, further investigation is warranted to confirm the findings.

Exposure characteristics of phthalate metabolites among the Zunyi cohort of pregnant women in Southwest China.

Reported evidence has increasingly indicated that exposure to phthalates can cause adverse pregnancy outcomes. However, phthalate exposure levels among pregnant women remains unclear. We aimed to evaluate the concentrations and predictors of phthalate metabolites in urine samples of the ongoing Zunyi cohort of pregnant women from Southwest China. The urine samples were collected from 1003 pregnant women during their third trimester of pregnancy. The concentrations of nine phthalate metabolites in urine samples were then determined. Data on socio-demographic profiles of the participants, lifestyle during pregnancy, parity, and sampling season were collected using questionnaires. The detectable rate of phthalate metabolites ranged from 76 to 100%. On average, mono-butyl phthalate exhibited the highest median concentration (62.45 µg/L), while mono-benzyl phthalate exhibited the lowest median concentration (0.04 µg/L). Urine concentrations of phthalate metabolites were significantly higher in older, multiparous, higher body mass index, higher income, and passive smoking during pregnancy participants. The levels of low-molecular-weight phthalate metabolites were highest during the summer. The findings indicate the health of pregnant women and fetuses in Zunyi may be generally harmed by the high exposure of phthalate metabolites, especially by mono-n-butyl phthalate. In addition, phthalate metabolites present a demographic and seasonal differential distribution among the study population. Targeted measures to reduce phthalate exposure for high-risk pregnant women and during high-exposure seasons may have potential benefits for maternal and fetal health protection.

Salidroside Ameliorates Cardiomyocyte Hypertrophy by Upregulating Peroxisome Proliferator-Activated Receptor-α.

Cardiac hypertrophy is an adaptive change in response to pressure overload, however the hypertrophy may evolve toward heart failure if cannot be corrected as soon as possible. The dysfunction of peroxisome proliferator-activated receptor-α (PPARα) plays a key role in cardiac hypertrophy. In the present study, salidroside inhibited the mRNA expressions of hypertrophic markers including atrial natriuretic factor and brain natriuretic peptide in a dosage-dependent manner. Furthermore, the protein expression and transcriptional activity of PPARα were increased by salidroside in H9C2 cells treated with angiotensin II, as well as the target genes of PPARα, while the situations were nearly reversed when PPARα was knocked down. Next, salidroside could elevate the expression of ATGL, a key upstream regulator of PPARα; the effects of salidroside including increasing PPARα function and inhibiting cardiomyocyte hypertrophy were impaired by ATGL knockdown. Our present studies suggested that salidroside elevated PPARα function to alleviate cardiomyocyte hypertrophy, which was involved in the increase of ATGL expression.

Prevalence of workplace violence against general practitioners: A systematic review and meta-analysis.

Global Conference on Primary Health Care identified that promoting the primary healthcare system has become an important work. Workplace violence (WPV) against GPs is an important global problem. This study aimed to summarise the evidence on the prevalence of WPV against GPs. We systematically searched the PubMed, Embase, and Web of Science databases, and the references of retrieved articles to identify studies on reporting the prevalence of WPV against GPs. We included 15 eligible studies in this meta-analysis. 63.1% (95% confidence interval (CI): 55.6%-70.6%) experienced any form of WPV, 33.8% (95% CI: 25.3%-42.3%) encountered non-physical violence, and 8.5% (95% CI: 5.7%-11.4%) reported experiencing physical violence. The proportion of physical violence differed across study location, sex, and practice setting, and the prevalence of physical violence increased with study period. No significant differences in the prevalence of non-physical violence in sex and study location were found. The prevalence of WPV against GPs is high. A higher prevalence of physical violence was found in some Asian countries (such as China), male GPs, and primary care.