Estrogen Oppositely Regulates Pulmonary Hypertension via METTL3/PFKFB3 Under Normoxia and Hypoxia.

Despite extensive investigation into estrogen's role in pulmonary hypertension (PH) development, its effects-whether beneficial or detrimental-remains contentious. This study aimed to elucidate estrogen's potential role in PH under normoxic and hypoxic conditions. Utilizing norfenfluramine- and hypoxia-induced rat models of PH, the study evaluated the impact of 17ß-estradiol (E2) on PH progression. E2 promoted PH development under normoxia while providing protection under hypoxia. Mechanistically, under normoxia, E2 upregulated methyltransferase-like 3 (METTL3) gene transcription and protein via an estrogen response element-dependent pathway, which in turn elevated the m6A methylation and translational efficiency of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 (PFKFB3) mRNA, leading to increased PFKFB3 protein levels and enhanced proliferation and migration of pulmonary artery smooth muscle cells (PASMCs). Conversely, under hypoxia, E2 downregulated METTL3 transcription through a hypoxia response element-dependent mechanism, driven by elevated hypoxia-induced factor 1α (HIF-1α) levels, resulting in reduced PFKFB3 protein expression and diminished PASMCs proliferation and migration. Both METTL3 and PFKFB3 proteins are upregulated in the pulmonary arteries of patients with PAH. Collectively, these findings suggest that E2 exerts differential effects on PH progression via dual regulation of the METTL3/PFKFB3 protein under normoxic and hypoxic conditions, positioning the METTL3/PFKFB3 protein as a potential therapeutic target for PH treatment.

Association between maternal lipid profiles and lipid ratios in early to middle pregnancy as well as their dynamic changes and gestational diabetes mellitus.

BACKGROUND: Unfavourable lipid and glucose levels may play a crucial role in the pathogenesis of gestational diabetes mellitus (GDM). However, there is a lack of prospective studies on the relationship between lipid profiles, lipid ratios and GDM during pregnancy. AIMS: To prospectively investigate the relationship between lipid profile and lipid ratios in early and mid-pregnancy and their pattern of change from early to mid-pregnancy and the risk of GDM. METHODS: This nested case-control study was based on maternal and child healthcare hospitals from Fujian Province, China. We included pregnant women who delivered in the hospital from January 2021 to June 2023. Lipid profiles (TC, TG, ApoA1, ApoB, HDL-c, LDL-c) and fasting glucose were measured before 14 weeks of gestation and between 20 and 28 weeks of gestation, and lipid ratios (triglyceride glucose index, TG/HDL-c and TC/HDL-c) was constructed. Logistic regression was used to assess the relationship between lipid profile, lipid ratios and GDM. RESULTS: Of 1586 pregnant women, 741 were diagnosed with GDM. After adjusting for potential confounders, TG, ApoA1, ApoB, LDL-c, triglyceride glucose index, TG/HDL-c, and TC/HDL-c in early pregnancy were positively associated with the risk of GDM (odds ratios [95% CI] for extreme interquartile comparisons were 2.040 (1.468-2.843), 1.506 (1.091-2.082), 1.529 (1.110-2.107), 1.504 (1.086-2.086), 1.952 (1.398-2.731), 2.127 (1.526-2.971), and 2.370 (1.700-3.312), all trend P < 0.05). HDL-c was negatively associated with the risk of GDM (0.639: 0.459-0.889, trend P all less than 0.05). Similarly, in mid-pregnancy, lower levels of HDL-c, higher levels of triglyceride glucose index, TG/HDL-c ratio, and TC/HDL-c ratio were associated with increased risk of GDM (all trends P < 0.05). Stably high levels (both ≥ median for early and mid-pregnancy) of triglyceride glucose index, TG/HDL-c and TC/HDL-c were associated with increased risk of GDM (OR [95% CI]: 2.369 (1.438-3.940), 1.588 (1.077-2.341), 1.921 (1.309-2.829), respectively). The opposite was true for HDL-c, where stable high levels were negatively associated with GDM risk (OR [95% CI]: 0.599 (0.405-0.883)). CONCLUSION: Increases in triglyceride glucose index, TG/HDL-c ratio, and TC/HDL-c ratio in early and mid-pregnancy, as well as their stable high levels from early to mid-pregnancy, are associated with a higher risk of GDM. In contrast, increased levels of HDL-c, both in early and mid-pregnancy, and their stable high levels from early to mid-pregnancy were associated with a lower risk of GDM. That highlighted their possible clinical relevance in identifying those at high risk of GDM.

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.

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.

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.

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.

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 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.

Assessment of Internet Hospitals in China During the COVID-19 Pandemic: National Cross-Sectional Data Analysis Study.

BACKGROUND: Internet hospitals in China are being rapidly developed as an innovative approach to providing health services. The ongoing COVID-19 pandemic has triggered the development of internet hospitals that promote outpatient service delivery to the public via internet technologies. To date, no studies have assessed China's internet hospitals during the COVID-19 pandemic. OBJECTIVE: This study aimed to elucidate the characteristics of China's internet hospitals and assess the health service capacity of these hospitals. METHODS: Data on 711 internet hospitals were collected from official websites, the WeChat (Tencent Inc) platform, smartphone apps, and the Baidu search engine until July 16, 2020. RESULTS: As of July 16, 2020, 711 internet hospitals were developed in mainland China. More than half of these internet hospitals (421/711, 59.2%) were established during 2019 (206/711, 29%) and 2020 (215/711, 30.2%). Furthermore, about one-third (215/711, 30.2%) of internet hospitals were established at the beginning of 2020 as an emergency response to the COVID-19 epidemic. The 711 internet hospitals consisted of the following 3 types of hospitals: government-oriented (42/711, 5.91%), hospital-oriented (143/711, 20.11%), and enterprise-oriented internet hospitals (526/711, 73.98%). The vast majority of internet hospitals were traditional hospitals (526/711, 74%). Nearly 46.1% (221/711) of internet hospitals requested doctors to provide health services at a specific web clinic. Most patients (224/639, 35.1%) accessed outpatient services via WeChat. Internet hospitals' consulting methods included SMS text messaging consultations involving the use of graphics (552/570, 96.8%), video consultations (248/570, 43.5%), and telephone consultations (238/570, 41.8%). The median number of available web-based doctors was 43, and the median consultation fees of fever clinics and other outpatient clinics were ¥0 (US $0) per consultation and ¥6 (US $0.93) per consultation, respectively. Internet hospitals have provided various services during the COVID-19 pandemic, including medical prescription, drug delivery, and medical insurance services. CONCLUSIONS: The dramatic increase of internet hospitals in China has played an important role in the prevention and control of COVID-19. Internet hospitals provide different and convenient medical services for people in need.

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.

17ß-Estradiol nongenomically induces vascular endothelial H2S release by promoting phosphorylation of cystathionine γ-lyase.

Estrogen exerts its cardiovascular protective role at least in part by regulating endothelial hydrogen sulfide (H2S) release, but the underlying mechanisms remain to be fully elucidated. Estrogen exerts genomic effects, i.e. those involving direct binding of the estrogen receptor (ER) to gene promoters in the nucleus, and nongenomic effects, mediated by interactions of the ER with other proteins. Here, using human umbilical vein endothelial cells (HUVECs), immunological detection, MS-based analyses, and cGMP and H2S assays, we show that 17ß-estradiol (E2) rapidly enhances endothelial H2S release in a nongenomic manner. We found that E2 induces phosphorylation of cystathionine γ-lyase (CSE), the key enzyme in vascular endothelial H2S generation. Mechanistically, E2 enhanced the interaction of membrane ERα with the Gα subunit Gαi-2/3, which then transactivated particulate guanylate cyclase-A (pGC-A) to produce cGMP, thereby activating protein kinase G type I (PKG-I). We also found that PKG-Iß, but not PKG-Iα, interacts with CSE, leading to its phosphorylation, and rapidly induces endothelial H2S release. Furthermore, we report that silencing of either CSE or pGC-A in mice attenuates E2-induced aorta vasodilation. These results provide detailed mechanistic insights into estrogen's nongenomic effects on vascular endothelial H2S release and advance our current understanding of the protective activities of estrogen in the cardiovascular system.

Scalable 2D Mesoporous Silicon Nanosheets for High-Performance Lithium-Ion Battery Anode.

Constructing unique mesoporous 2D Si nanostructures to shorten the lithium-ion diffusion pathway, facilitate interfacial charge transfer, and enlarge the electrode-electrolyte interface offers exciting opportunities in future high-performance lithium-ion batteries. However, simultaneous realization of 2D and mesoporous structures for Si material is quite difficult due to its non-van der Waals structure. Here, the coexistence of both mesoporous and 2D ultrathin nanosheets in the Si anodes and considerably high surface area (381.6 m2 g-1 ) are successfully achieved by a scalable and cost-efficient method. After being encapsulated with the homogeneous carbon layer, the Si/C nanocomposite anodes achieve outstanding reversible capacity, high cycle stability, and excellent rate capability. In particular, the reversible capacity reaches 1072.2 mA h g-1 at 4 A g-1 even after 500 cycles. The obvious enhancements can be attributed to the synergistic effect between the unique 2D mesoporous nanostructure and carbon capsulation. Furthermore, full-cell evaluations indicate that the unique Si/C nanostructures have a great potential in the next-generation lithium-ion battery. These findings not only greatly improve the electrochemical performances of Si anode, but also shine some light on designing the unique nanomaterials for various energy devices.

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.

Associations of air pollutants and related metabolites with preterm birth during pregnancy.

OBJECTIVE: This study aimed to investigate the influence of exposure to ambient fine particulate matter (PM2.5) and its components during pregnancy on the prevalence of preterm birth (PTB). Additionally, we sought to identify the susceptible exposure window. Furthermore, we explored the potential mediating role of blood analysis and a comprehensive metabolic panel in the association between pollutant exposure and PTB incidence. METHODS: This birth cohort study recruited 139 participants with PTB outcomes and 1713 controls from Fujian Maternal and Child Health Hospital between January 2021 and June 2023. Sociodemographic characteristics and clinical treatment data during participants' first pregnancies were collected. The exposure levels to pollutants during pregnancy were estimated via a combined geographic-statistical model utilising satellite remote sensing data. The distributional lag nonlinear modelling was employed to assess associations between pollutant exposure during pregnancy and the prevalence of PTB. Weighted quantile regression was used to identify key components associated with PM2.5 and PTB during pregnancy. Additionally, a mediating effect analysis was conducted to evaluate the role of blood analysis. The metabolic profile was used to screen for differentially abundant metabolites associated with PTB and explore their relative expression in relation to air pollutants and PTB incidence. RESULTS: Following the adjustment for potential confounding variables, the mean weekly susceptibility windows for PM2.5 were identified as 7-10, 16-19, and 22-28 weeks; 8-10, and 15-19 weeks for inorganic sulfate; 6-10, and 15-28 weeks for nitrate; 6-12, and 15-28 weeks for ammonium (NH4+); and 7-9, 18-20, and 22-36 weeks for organic matter. During mixed exposure to PM2.5 components, the key component is NH4+. In the mixed exposure to PM2.5 components, NH4+ emerged as a key contributor. The results of the mediation analysis revealed that haemoglobin played a mediating role, accounting for 21.53 % of the association between exposure to environmental pollutants and the prevalence of PTB. It is noteworthy that, no mediating effects were observed for the other variables. Furthermore, non-targeted metabolomics identified 17 metabolites associated with PTB. Among these factors, hydrogen phosphate may impact metabolic pathways such as oxidative phosphorylation, influencing the risk of PTB. The interplay between environmental pollutants and metabolites, particularly through oxidative phosphorylation pathways, may contribute to PTB incidence. CONCLUSIONS: The evidence indicates that exposure to PM2.5 and its components during pregnancy were a significant risk factor for PTB. Notably, specific weekly exposure windows were identified for pollutants during pregnancy. Among the PM2.5 components, NH4+ exhibited the most substantial weight in the association analysis between exposure to the mixture of components and PTB. Furthermore, our mediation analysis revealed that haemoglobin serves as a partial mediator in the relationship between exposure to pollutants during pregnancy and the prevalence of PTB. Additionally, maternal serum metabolic profiles differed between the preterm and control groups. Notably, a combined effect involving hydrogen phosphate and mixed exposure to PM2.5 fractions further contributed to the development of PTB. Oxidative phosphorylation pathways may play pivotal roles in this intricate association.

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.

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.

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.

Large-scale cubic InN nanocrystals by a combined solution- and vapor-phase method under silica confinement.

Large-scale cubic InN nanocrystals were synthesized by a combined solution- and vapor-phase method under silica confinement. Nearly monodisperse cubic InN nanocrystals with uniform spherical shape were dispersed stably in various organic solvents after removal of the silica shells. The average size of InN nanocrystals is 5.7 ± 0.6 nm. Powder X-ray diffraction results indicate that the InN nanocrystals are of high crystallinity with a cubic phase. X-ray photoelectron spectroscopy and energy-dispersive spectroscopy confirm that the nanocrystals are composed of In and N elements. The InN nanocrystals exhibit infrared photoluminescence at room temperature, with a peak energy of ~0.62 eV, which is smaller than that of high-quality wurtzite InN (~0.65-0.7 eV) and is in agreement with theoretical calculations. The small emission peak energy of InN nanocrystals, as compared to other low-cost solution or vapor methods, reveals the superior crystalline quality of our samples, with low or negligible defect density. This work will significantly promote InN-based applications in IR optoelectronic device and biology.