FSH induces EMT in ovarian cancer via ALKBH5-regulated Snail m6A demethylation.

Background: The therapeutic benefits of targeting follicle-stimulating hormone (FSH) receptor in treatment of ovarian cancer are significant, whereas the role of FSH in ovarian cancer progresses and the underlying mechanism remains to be developed. Methods: Tissue microarray of human ovarian cancer, tumor xenograft mouse model, and in vitro cell culture were used to investigate the role of FSH in ovarian carcinogenesis. siRNA, lentivirus and inhibitors were used to trigger the inactivation of genes, and plasmids were used to increase transcription of genes. Specifically, pathological characteristic was assessed by histology and immunohistochemistry (IHC), while signaling pathway was studied using western blot, quantitative RT-PCR, and immunofluorescence. Results: Histology and IHC of human normal ovarian and tumor tissue confirmed the association between FSH and Snail in ovarian cancer metastasis. Moreover, in epithelial ovarian cancer cells and xenograft mice, FSH was showed to promote epithelial mesenchymal transition (EMT) progress and metastasis of ovarian cancer via prolonging the half-life of Snail mRNA in a N6-methyladenine methylation (m6A) dependent manner, which was mechanistically through the CREB/ALKBH5 signaling pathway. Conclusions: These findings indicated that FSH induces EMT progression and ovarian cancer metastasis via CREB/ALKBH5/Snail pathway. Thus, this study provided new insight into the therapeutic strategy of ovarian cancer patients with high level of FSH.

Follicle-stimulating hormone accelerates osteoclast migration by enhancing methyltransferase-like 3-mediated m6A methylation of cathepsin K.

Follicle-stimulating hormone (FSH) accelerates osteoporosis in postmenopausal women, while the underlying mechanism remains uncharacterized. N6-methyladenosine (m6A) is one of the most important regulations in the development of osteoporosis. In this study, we aimed to investigate the role of FSH in m6A modification and osteoclast function. Here, we showed that FSH upregulated m6A levels in osteoclasts via stimulating methyltransferase-like 3 (METTL3) protein expression. FSH enhanced osteoclast migration, while the knockdown of METTL3 eliminated this enhancement. Both MeRIP-seq and RNA sequencing identified that cathepsin K (CTSK) is the potential downstream target of METTL3. Knockdown of CTSK reduced FSH-upregulated osteoclast migration. Furthermore, silencing METTL3 decreased CTSK mRNA stability. Finally, FSH induced phosphorylation of cyclic-AMP response element-binding protein (CREB), while silencing of CREB attenuated the effects of FSH on the promoter transcriptional activity of Mettl3 and CTSK/METTL3 protein. Taken together, these findings indicate that FSH promotes osteoclast migration via the CREB/METTL3/CTSK signaling pathway, which may provide a potential target for suppressing osteoclast mobility and postmenopausal osteoporosis therapy.

Association between longitudinal dietary patterns and changes in obesity: a population-based cohort study.

Introduction: Research on the trajectory of dietary patterns and changes in obesity has been inconclusive. Methods: This study described the dietary intake and adiposity trajectories of Chinese adults and assessed the association between dietary trajectories and changes in body mass index (BMI) and waist-to-hip ratio (WHR). We used data from 3, 643 adults who participated in the China Health and Nutrition Survey from 1997 to 2015. Detailed dietary data were collected by conducting three consecutive 24-h recalls. Multitrajectories of diet scores were identified by a group-based multitrajectory method. We described the change in BMI and WHR using group-based trajectory modeling. We assessed the associations between dietary trajectories and changes in people with obesity using a logistic regression model. Results: Our study revealed four trajectories of low-carbohydrate (LCD) and low-fat diet (LFD) scores. Three adiposity trajectories were identified according to the baseline level and developmental trend of BMI and WHR. Compared with the reference group, which was characterized by sustained healthy dietary habits with healthy diet scores at baseline and sustained maintenance of healthy diet scores, the other three diet trajectories had a higher risk of falling into the adverse adiposity trajectory. Discussion: Maintaining a healthy LCD and LFD can markedly decrease the risk of adiposity.

Exploring the association between circRNA expression and pediatric obesity based on a case-control study and related bioinformatics analysis.

OBJECTIVE: Our present study utilized case-control research to explore the relationship between specific circRNAs and pediatric obesity through a literature review and bioinformatics and to predict their possible biological functions, providing ideas for epigenetic mechanism studies of pediatric obesity. METHODS: CircRNAs related to pediatric obesity were preliminarily screened by a literature review and qRT-PCR. CircRNA expression in children with obesity (n = 75) and control individuals (n = 75) was confirmed with qRT-PCR in a case-control study. This was followed by bioinformatics analyses, such as GO analysis, KEGG pathway analysis, and ceRNA network construction. Multivariate logistic regression was utilized to analyze the effects of circRNAs on obesity. A receiver operating characteristic (ROC) curve was also drawn to explore the clinical application value of circRNAs in pediatric obesity. RESULTS: Has_circ_0046367 and hsa_circ_0000284 were separately validated to be statistically downregulated and upregulated, respectively, in the peripheral blood mononuclear cells of children with obesity and revealed as independent indicators of increased CHD risk [hsa_circ_0046367 (OR = 0.681, 95% CI: 0.480 ~ 0.967) and hsa_circ_0000284 (OR = 1.218, 95% CI: 1.041 ~ 1.424)]. The area under the ROC curve in the combined analysis of hsa_circ_0046367 and hsa_circ_0000284 was 0.706 (95% CI: 0.623 ~ 0.789). Enrichment analyses revealed that these circRNAs were actively involved in neural plasticity mechanisms, cell secretion and signal regulation. CONCLUSION: The present research revealed that low expression of hsa_circ_0046367 and high expression of hsa_circ_0000284 are risk factors for pediatric obesity and that neural plasticity mechanisms are closely related to obesity.

Mutation of aspartic acid 262 on estrogen receptor abrogates estradiol signaling pathway.

OBJECTIVE: ERα (estrogen receptor alpha) exerts nuclear genomic actions and membrane-initiated non-genomic effects. The mutation of aspartic acid into alanine in vitro revealed the critical role of aspartic acid 258 (corresponding to mouse amino acid site 262) of ERα for non-nuclear function. Our previous in vitro study revealed that this mutation blocked estrogen's non-genomic effects on vascular endothelial H2S release. Here, we studied the in vivo role of the aspartic acid 262 of ERα in the reproductive system and in the vascular tissue. APPROACH AND RESULTS: We generated a mouse model harboring a point mutation of the murine counterpart of this aspartic acid into alanine (ERαD262A). Our results showed that the ERαD262A females are fertile with standard hormonal serum levels, but the uterine development and responded with estrogen and follicular development are disrupted. In line with our previous study, we found that the rapid dilation of the aorta was abrogated in ERαD262A mice. In contrast to the previously reported R264-ERα mice, the classical estrogen genomic effector SP1/NOS3/AP1 and the nongenomic effectors p-eNOs, p-AKT, and p-ERK were disturbed in the ERαD262A aorta. Besides, the serum H2S concentration was decreased in ERαD262A mice. Together, ERαD262A mice showed compromised both genomic and non-genomic actions in response to E2. CONCLUSIONS: These data showed that aspartic acid 262 of ERα are important for both genomic and non-genomic effects of E2. Our data provide a theoretical basis for further selecting an effective non-genomic mouse model and provide a new direction for developing estrogen non-genomic effect inhibitors.

Hyperuricemia and coronary heart disease: The mediating role of blood pressure and thrombospondin 3.

BACKGROUND & AIMS: Although hyperuricemia is a known risk factor for coronary heart disease (CHD), little is known about the role of blood pressure in mediating this association. The purpose of this study is to investigate the role of blood pressure-related indicators and Thrombospondin 3 (THBS3) in the association between hyperuricemia and CHD. METHODS AND RESULTS: Our observational epidemiology study included 593 CHD cases and 760 controls from a residential stable sample. We also chose 43 new CHD patients and 43 controls to test the expression levels of THBS3 using ELISA kits. We used logistic regression models and mediating effect analysis to investigate the relationships between hyperuricemia and CHD, as well as the mediating role of blood pressure-related indicators and THBS3. In the general population (OR: 2.001 [95% CI: 1.528-2.622]), male population (OR: 1.591 [95% CI: 1.119-2.262]), and female population (OR: 2.813 [95% CI: 1.836-4.310]), hyperuricemia is an independent risk factor for CHD. In general, average systolic blood pressure (SBP) and average pulse pressure difference (PPD) mediated 3.35% and 4.59%, respectively, of the association between hyperuricemia and CHD, and 6.60% and 6.60% in women. However, in the male population, we have not yet found that blood pressure-related indicators had a significant mediating effect. Meanwhile, we found that THBS3 mediated 19.23% of the association between hyperuricemia and CHD. CONCLUSIONS: Average SBP, PPD, and THBS3 all play a role in the association of hyperuricemia and CHD. In the female population, similar mediating results in blood pressure-related indicators were observed.

Association of longitudinal patterns of nighttime sleep duration and daytime napping duration with risk of multimorbidity.

OBJECTIVES: To determine whether longitudinal trajectories of nighttime sleep duration and daytime napping duration are related to subsequent multimorbidity risk. To explore whether daytime napping can compensate for negative effects of short nighttime sleep. METHODS: The current study included 5262 participants from China Health and Retirement Longitudinal Study. Self-reported nighttime sleep duration and daytime napping duration were collected from 2011 to 2015. The 4-year sleep duration trajectories were conducted by group-based trajectory modeling. The 14 medical conditions were defined by self-reported physician diagnoses. Multimorbidity was diagnosed as participants with 2 or more of the 14 chronic diseases after 2015. Associations between sleep trajectories and multimorbidity were assessed by Cox regression models. RESULTS: During 6.69 years of follow-up, we observed multimorbidity in 785 participants. Three nighttime sleep duration trajectories and three daytime napping duration trajectories were identified. Participants with persistent short nighttime sleep duration trajectory had the higher risk of multimorbidity (hazard ratio = 1.37, 95% confidence interval: 1.06-1.77), compared with those with persistent recommended nighttime sleep duration trajectory. Participants with persistent short nighttime sleep duration and persistent seldom daytime napping duration had the highest risk of multimorbidity (hazard ratio = 1.69, 95% confidence interval: 1.16-2.46). CONCLUSIONS: In this study, persistent short nighttime sleep duration trajectory was associated with subsequent multimorbidity risk. Daytime napping could compensate for the risk of insufficient night sleep.

Life-course fertility and multimorbidity among middle-aged and elderly women in China: Evidence from China health and retirement longitudinal study.

Background: Multimorbidity has become an important public health problem in China, especially among middle-aged and elderly women. Few studies have been reported on the association between multimorbidity and female fertility, which is an important stage in the life course. This study aimed to explore the association between multimorbidity and fertility history among middle-aged and elderly women in China. Methods: Data from 10,182 middle-aged and elderly female participants in the China Health and Retirement Longitudinal Study (CHARLS) in 2018 were used in this study. Multimorbidity was defined as the presence of at least two or more chronic conditions. Logistic regression analysis, negative binomial regression analysis, and restrictive cubic splines (RCSs) were used to analyze the relationship between female fertility history and multimorbidity or the number of chronic conditions. Multivariable linear regression was used to analyze the relationship between female fertility history and multimorbidity pattern factor scores. Results: The results of this study showed that high parity and early childbearing were significantly associated with an increased risk of multimorbidity and an increased number of chronic conditions among middle-aged and elderly women in China. Late childbearing was significantly associated with reduced risk of multimorbidity and lessened diseases. Parity and age of first childbirth were significantly correlated with the odds of multimorbidity. The association between fertility history and multimorbidity was found to be influenced by age and urban-rural dual structure. Women with high parity tend to have higher factor scores of cardiac-metabolic, visceral-arthritic, and respiratory-psychiatric patterns. Women with early childbearing tended to have higher factor scores of the visceral-arthritic pattern and those with late childbearing tended to have lower factor scores of the cardiac-metabolic pattern. Conclusion: Fertility history has a significant effect on multimorbidity in the middle and later lives of Chinese women. This study is of great importance for reducing the prevalence of multimorbidity among Chinese women through their life course and promoting health during their middle and later lives.

Association between polyfluoroalkyl substances exposure and sex steroids in adolescents: The mediating role of serum albumin.

BACKGROUND: Polyfluoroalkyl substances (PFASs) are an emerging class of contaminants with endocrine disrupting hazards. The impact of PFASs exposure on sex steroids remain inconclusive. METHODS: This study used data from the 2013-2016 National Health and Nutrition Examination Survey (NHANES), including 525 adolescents aged 12-19. We explored the association between serum PFASs and sex steroids using multiple linear regression, weighted quantified sum (WQS) regression, and Bayesian kernel machine regression (BKMR). Mediation analyses were performed to assess whether serum albumin mediates the effects of PFASs on sex steroids. RESULTS: Single exposure to perfluorohexane sulfonic acid (PFHxS) or n-perfluorooctanoic acid (n-PFOA) was found to be inversely associated with sex hormone binding protein (SHBG) after adjustment for confounders. Results from both the WQS and BKMR models showed that mixed exposure to the five PFASs was negatively associated with SHBG and testosterone (TT) in all adolescents, while only in the WQS model, the mixed exposure to PFASs was negatively correlated with E2 and FAI in boys and negatively correlated with TT and SHBG in girls. Serum albumin was found to possibly mediate 9.7 % of the association between mixed PFAS exposure and TT, and 9.7 % of the association between mixed PFAS exposure and SHBG. CONCLUSION: Our study demonstrates a negative association between mixed exposure to PFASs and adolescent TT and SHBG levels, and suggests that albumin may merit further study as a potential target for PFAS harm reduction.

Circ_0000284: A risk factor and potential biomarker for prehypertension and hypertension.

CircRNAs have been shown to be involved in the development of certain diseases, but their application in prehypertension and hypertension remains unclear. We aimed to explore the potential role of circ_0000284 in revealing the molecular regulatory mechanisms of prehypertension and hypertension. We enrolled a total of 100 patients with normal blood pressure, 100 patients with prehypertension and 100 patients with hypertension. The expression of circ_0000284 among the groups was detected by real-time fluorescence quantitative polymerase chain reaction (qRT‒PCR). Multivariate logistic models were constructed combining conventional risk factors with circ_0000284. A receiver operating characteristic curve (ROC) was used to analyze the diagnostic value of circRNAs in the clinical model. Spearman correlation was used to analyze the correlation of circ_0000284 and the biochemical characteristics of all subjects. The results showed that circ_0000284 was differentially expressed among the normal blood pressure group, prehypertensive group and hypertensive group and showed a significantly upregulated trend in the progression to hypertension (P < 0.05). The ROC curve revealed a high diagnostic ability of circ_0000284 in hypertension in the clinical model (AUC = 0.812). Circ_0000284 also presented a certain ability for early diagnosis of prehypertension (AUC = 0.628). Spearman correlation showed that circ_0000284 was positively correlated with Na and CKMB. Our study suggested that upregulated expression of circ_0000284 was an independent risk factor for prehypertension and hypertension. Circ_0000284 was a potential fingerprint for the early diagnosis of hypertension and distinguished the intermediate stage of hypertension development. Moreover, our study provided new insight into the correlation between circ_0000284 and cardiac injury in the progression to hypertension.

Physical Changes of Preschool Children during COVID-19 School Closures in Fujian, China.

The COVID-19 pandemic may constitute an "obesogenic lifestyle" that results in exacerbating childhood obesity. However, studies investigating regional sociodemographic factors including different age groups or sexes in children with obesity are lacking. We aimed to clarify the high obesity prevalence populations of preschool children to provide a regional basis for children's health policy during the COVID-19 school closures. From May to September 2019, a total of 29,518 preschool children were included in a large sample, multicenter cross-sectional study to explore physical status in Fujian Province by stratified cluster random sampling. In October 2019 and October 2020, we also conducted a cross-sectional study exploring physical development including changes in height, weight, and BMI of 1688 preschool children in Fuzhou before and after the COVID-19 school closures. Student' s t-test, Mann-Whitney U test, or chi-square test was used to assess differences in physical development and overweight and obesity rates among preschool children before and after school closures. For regional factors, the weight of urban preschool children of all ages became higher after the outbreak (p (age 3-4) = 0.009; p (age 4-5) < 0.001; p (age 5-6) = 0.002). For sex factors, overweight and obesity in boys had a greater prevalence than in girls before and after the outbreak. In four age groups, overweight and obesity rates in the 5-year-old group (15.5% and 9.9%) were higher than before (11.4% and 6.0%). The weight and BMI of 4- to 5-year-old children also increased faster than before (p < 0.001). The COVID-19 pandemic has promoted the epidemic of childhood obesity. Living in urban/coastal (economically developed) areas, boys, and aged 4-6 years old may be a susceptible population to obesity development after the outbreak.

Association between fine particulate matter and coronary heart disease: A miRNA microarray analysis.

Several studies have reported an association between residential surrounding particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5) and coronary heart disease (CHD). However, the underlying biological mechanism remains unclear. To fill this research gap, this study enrolled a residentially stable sample of 942 patients with CHD and 1723 controls. PM2.5 concentration was obtained from satellite-based annual global PM2.5 estimates for the period 1998-2019. MicroRNA microarray and pathway analysis of target genes was performed to elucidate the potential biological mechanism by which PM2.5 increases CHD risk. The results showed that individuals exposed to high PM2.5 concentrations had higher risks of CHD than those exposed to low PM2.5 concentrations (odds ratio = 1.22, 95% confidence interval: 1.00, 1.47 per 10 µg/m3 increase in PM2.5). Systolic blood pressure mediated 6.6% of the association between PM2.5 and CHD. PM2.5 and miR-4726-5p had an interaction effect on CHD development. Bioinformatic analysis demonstrated that miR-4726-5p may affect the occurrence of CHD by regulating the function of RhoA. Therefore, individuals in areas with high PM2.5 exposure and relative miR-4726-5p expression have a higher risk of CHD than their counterparts because of the interaction effect of PM2.5 and miR-4726-5p on blood pressure.

Sleep health and its related influencing factors in primary and middle school students in Fuzhou: A large multi-center cross-sectional study.

Background: This current study set out to investigate the status of sleep health in 7-20-year-old students in Fuzhou and explore the related influencing factors of sleep health. Methods: A total of 38,467 children and adolescents in Fuzhou were included in the study through a random stratified cluster sampling. Data were collected from May to June 2019, in 18 primary schools and 18 middle schools from nine districts, Fuzhou. Children's parents and adolescents of sampled classes were invited to fill out a series of questionnaires about the performance of the last 6 months (sociodemographic characteristics, sleep-related lifestyle behaviors, and electronic-products usage). Multiple linear regression was carried out to analyze data. Results: Of the total 40,888 questionnaires we released, 38,467 were valid and effective with the response rate was 94.08%. The age of the surveyed participants was 11.85 ± 3.1, including 20,013 boys and 18,454 girls. The multiple linear regression analysis identified factors associated with sleep health (p < 0.05): Boy (coef = 0.073, 95% CI: 0.030-0.115), age (coef = 1.797, 95% CI: 0.224-0.243), key school (coef = 2.069, 95% CI: 0.105-0.193), urban (coef = 0.096, 95% CI: 0.054-0.139), excessive daytime sleepiness (coef = 0.535, 95% CI: 0.432-0.639), unhealthy sleep habits (coef = 0.363, 95% CI: 0.307-0.419), eating before sleep (coef = 0.578, 95% CI: 0.527-0.630), using electronic products in bedroom (coef = 0.074, 95% CI: 0.028-0.121), screen time per day during school (coef = 0.260, 95% CI: 0.235-0.284), frequency of using electronics 30 min before bedtime (coef = 0.150, 95% CI: 0.134-0.166), strained relationship with parents (coef = 0.361, 95% CI: 0.270-0.452), strained relationship with peers (coef = 0.267, 95% CI: 0.171-0.363), excessive homework or learning (coef = 0.189, 95% CI: 0.141-0.237), time for doing homework (coef = 0.266, 95% CI: 0.245-0.287), and mood swings frequently (coef = 1.174, 95% CI: 1.127-1.221) negatively impact sleep health. Sleep alone (coef = -0.204, 95% CI: -0.262-0.147) were the risk factors for sleep health. Furthermore, frequent mood swings was considered the most influential factor on overall variables. Conclusions: Sleep health is associated with factors covered sociodemographic characteristics, family sleep habits, and routine activities before bedtime. Multiple measures should be taken to improve sleep quality in a targeted manner.

Quality consistency evaluation on three species of North Patrininae herba by high-performance liquid chromatography coupled with electrospray ion trap time-of-flight mass spectrometry and network pharmacology approaches.

North Patrininae herba, a perennial herbaceous plant, has long been used in traditional Chinese medicine to treat appendicitis, enteritis, and dysentery. Sonchus arvensis L., Sonchus oleraceus L., and Ixeris chinensis (Thunb.) Nakai are used as substitutes for North Patrininae in different regions, but the consistency of chemical composition and efficacy of these three species is still unknown. In this study, a detailed chemical analysis was carried out of the extract obtained from Sonchus arvensis L., Ixeris chinensis (Thunb.) Nakai and Sonchus oleraceus L. and a chemical component not previously reported in Ixeris chinensis (Thunb.) Nakai was found-Luteolin-7-O-(6''-malonylglucoside). The mechanism of action of the extract against inflammation and type II diabetes was investigated using network pharmacology and analysis of blood-absorbed components following oral dosing of rats. Finally, a highly accurate and reliable method was established for quality control purposes. The results showed that Sonchus arvensis L. and Sonchus oleraceus L. may be considered potential resources of a medicinal compound, whereas Ixeris chinensis (Thunb.) Nakai requires further evaluation.

Association between sleep and multimorbidity in Chinese elderly: Results from the Chinese Longitudinal Healthy Longevity Survey (CLHLS).

OBJECTIVE: Abnormal sleep duration and poor sleep quality were associated with multiple diseases. However, the association between sleep behavior (including sleep duration and quality) and multimorbidity among the elderly remains unclear. Thus, our study aimed to explore this association in the Chinese elderly. METHODS: We conducted a cross-sectional study using data from the Chinese Longitudinal Healthy Longevity Survey (2014 wave). Nineteen chronic diseases were used to measure multimorbidity. Self-reported nighttime sleep duration and sleep quality were used as exposures. Multivariate logistic regression analysis and stratification were used to explore the association between sleep behavior and multimorbidity in different groups. Restrictive cubic splines were used to examine the exposure-response relationship. RESULTS: Compared with those with nighttime sleep duration between 7 and 9 h, participants with shorter (<7 h) and longer (>9 h) sleep duration had a higher prevalence of multimorbidity (odds ratio [OR], 95% confidence interval [CI] were 1.38, 1.18-1.61 and 1.30, 1.09-1.56 respectively). Besides, poor sleep quality (OR = 2.25, 95% CI:1.82-2.72) and moderate sleep quality (OR = 1.35, 95% CI:1.16-1.58) were positively associated with multimorbidity. CONCLUSIONS: Although the role of sleep behavior in multimorbidity has not been fully understood, this study highlighted the importance of normal nighttime sleep duration and good sleep quality in preventing multimorbidity.

Association between greenness and dyslipidemia in patients with coronary heart disease: A proteomic approach.

BACKGROUND: Residential surrounding greenness may be protective of dyslipidemia are often theorized but remain poorly quantified. In particular, the underlying biological mechanisms of blood lipid changes with green spaces remain unclear. METHODS: Our observational epidemiology study included a residentially stable sample of 1035 coronary heart disease patients, and proteomics study included 16 participants. Normalized Difference Vegetation Index (NDVI) was used to evaluate residential greenness exposures. Proteomics technology was used to identify plasma greenness-related proteome disturbance, and the pathway analysis was employed to evaluate the potential biological mechanisms of greenness decreasing dyslipidemia risk. RESULT: Higher residential surrounding greenness in the 500-m area was associated with lower risks of dyslipidemia (odds ratio (OR) = 0.871, 95% confidence interval (CI): 0.763, 0.994 for per one-quartile NDVI increase). Lymphocytes mediated 18.7% of the association between greenness and dyslipidemia. Greenness related proteins (including PLXDC1, IGFBP2 and LY6D) may regulate the biological functions of lipid metabolism and transport-related proteins (including ADIPOQ and CES1) through a series of biological processes. CONCLUSION: People in greener surroundings have a lower risk of dyslipidemia, which may be due to their lower inflammation, stronger lipid transporter activity, and normal cholesterol metabolism.

17ß-estradiol promotes angiogenesis through non-genomic activation of Smad1 signaling in endometriosis.

17ß-estradiol (E2) plays a key role in endometriosis through regulation of angiogenesis. Smad1 has been reported to be up-regulated in patients with endometriosis. However, the role of Smad1 in E2-mediated angiogenesis during the development of endometriosis remains to be determined. This study aimed to explore the role of Smad1 in E2-mediated angiogenesis during endometriosis and its underlying mechanisms. Immunofluorescence staining and Western blotting were performed to examine the expression of p-Smad1 in ectopic and control endometrium. Western blotting was used to examine activation of Smad1 signaling in NMECs, EMECs and HUVECs. Tube formation assay was performed to examine the effect of E2 on angiogenesis. Cell proliferation and migration was determined using in real-time by xCELLigence RTCA DP instrument. We found that the expression of p-Smad1 was significantly up-regulated in ectopic endometrium and ectopic intima microvascular endothelial cells. E2 non-genomically stimulated phosphorylation of Smad1 in HUVECs. c-Src and p44/42 MAPK(ERK1/2) signaling pathways are required for E2's induction on Smad1 phosphorylation. Moreover, caveolae is involved in E2-induced Smad1 phosphorylation in vascular endothelial cells. E2 promoted tube formation of vascular endothelial cells through c-Src/ERK1/2/Smad1 signaling pathway. Knockdown of Smad1 expression attenuated E2-induced proliferation and migration of HUVECs. In conclusion, E2 promotes proliferation, migration and tube formation of HUVECs through c-Src/ERK1/2/Smad1 signaling pathway. Our data shed new lights on the mechanisms through which E2 contributes to endometriosis, and may provide novel strategies to treat endometriosis.

Associations between meteorological variation and rupture of intracranial aneurysm in Fujian, China: A 5-year multicenter study.

OBJECTIVE: By exploring the exposure-response relationships between meteorological factors and rupture of intracranial aneurysm (IA) to reveal the influence of meteorological variation on IA rupture under the specific climate in Fujian, China. METHOD: 7515 cases of IA rupture from several municipal medical institutions in Fujian Province as well as local meteorological data during the same period were collected from 2013 to 2017. Poisson regression and Spearman correlation analysis were applied to explore the distribution characteristics of IA rupture and how it is associated with meteorological parameters. Poisson generalized additive model was established to further analyze the exposure-response relationships between meteorological factors and IA rupture, and its hysteresis effects. RESULT: The IA rupture exhibited a negative correlation with temperature (rs = -0.323, 95% CI: -0.539 ~ -0.068) and a positive correlation with atmospheric pressure (rs = 0.397, 95% CI: 0.152-0.597) or pressure difference (rs = 0.296, 95% CI: 0.038-0.517), 21.05 â„ƒ and 1000.14 hPa were the risk thresholds for the onset ascribed to variation in temperature and atmospheric pressure, respectively. Temperature and atmospheric pressure also exerted hysteresis effects on IA rupture. Cold will increase the rupture risk in the subsequent 1-3 days, and high pressure will raise the morbidity in the next 1-2 days. Besides, drastic variations in temperature and atmospheric pressure were also associated with the higher risk of IA rupture in the next 2 days and 1 day, respectively. CONCLUSION: Temperature and atmospheric pressure have a negative and positive correlation with IA rupture in Fujian, China, respectively. Variation in temperature and atmospheric pressure exert different degrees of hysteresis effects on IA rupture.

Large-Scale Spraying of Roads with Water Contributes to, Rather Than Prevents, Air Pollution.

Spraying roads with water on a large scale in Chinese cities is one of the supplementary precaution or mitigation actions implemented to control severe air pollution events or heavy haze-fog events in which the mechanisms causing them are not yet fully understood. These air pollution events were usually characterized by higher air humidity. Therefore, there may be a link between this action and air pollution. In the present study, the impact of water spraying on the PM2.5 concentration and humidity in air was assessed by measuring chemical composition of the water, undertaking a simulated water spraying experiment, measuring residues and analyzing relevant data. We discovered that spraying large quantities of tap or river water on the roads leads to increased PM2.5 concentration and humidity, and that daily continuous spraying produces a cumulative effect on air pollution. Spraying the same amount of water produces greater increases in humidity and PM2.5 concentration during cool autumn and winter than during hot summer. Our results demonstrate that spraying roads with water increases, rather than decreases, the concentration of PM2.5 and thus is a new source of anthropogenic aerosol and air pollution. The higher vapor content and resultant humidity most likely create unfavorable meteorological conditions for the dispersion of air pollution in autumn and winter with low temperature.

Association Between Circular RNAs and Intracranial Aneurysm Rupture Under the Synergistic Effect of Individual Environmental Factors.

Introduction: To study the association between specific circular RNAs and rupture of intracranial aneurysm. To explore its clinical diagnostic significance and synergistic effects with individual environmental influencing factors. Methods: Three hundred and forty seven cases and controls were included in this study. Multivariate analysis was used to explore the main individual environmental factors. Intracranial aneurysm rupture related circular RNAs screened based on sequencing was verified in peripheral blood by PCR. ROC curve, logistic regression model and fork analysis were used to study the association, diagnostic values, and synergistic effects of circular RNA with intracranial aneurysms and individual environmental factors. Results: Smoking, hair dyeing, sitting time ≥6 h/day, single animal oil intake and hypertension are the main risk factors for intracranial aneurysm rupture; People with higher education, sleeping time ≥7 h/day, tea drinking, diabetes, higher levels of (hemoglobin, low density lipoprotein, serum calcium, and apolipoprotein-A1) have a low risk of intracranial aneurysm rupture. Hsa_circ_0008433 and hsa_circ_0001946 are closely related to intracranial aneurysm rupture and have certain clinical diagnostic significance (AUC = 0.726; 95% CI: 0.668~0.784). Hsa_circ_0008433 (OR = 0.497, 95% CI: 0.338~0.731), hsa_circ_0001946 (OR = 0.682, 95% CI: 0.509~0.914) were independent epigenetic factors affecting intracranial aneurysm rupture, and have a multiplicative interaction with age (OR = 3.052, 95% CI: 1.006~9.258). Conclusions: Low expressions of hsa_circ_0008433 and hsa_circ_0001946 are risk factors for intracranial aneurysms rupture and have good clinical diagnostic value. There was a multiplicative interaction between epigenetic score and age. The older and the higher the epigenetic score was, the more likely to have intracranial aneurysm rupture.