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BACKGROUND: Perchlorate, nitrate, and thiocyanate are widely recognized as endocrine disrupting chemicals, which are closely related to thyroid function. Animal and human studies show a correlation between thyroid hormone and bone mineral density (BMD). However, it remains unknown whether perchlorate, nitrate, and thiocyanate were associated with BMD. This study aimed to explore the association between perchlorate, nitrate, and thiocyanate exposure with BMD. METHOD: A cross-sectional analysis among 5607 participants from the 2011-2018 National Health and Nutrition Examination Survey (NHANES) was conducted in the present study. Perchlorate, nitrate, and thiocyanate were detected in urine by ion chromatography. Survey-weighted generalized linear regression, restricted cubic splines, and qgcomp models were used to assess the association of BMDs with single and mixed perchlorate, nitrate, and thiocyanate exposures. In addition, age, gender, and BMI stratified these associations. RESULTS: Negative associations were found between perchlorate and nitrate with BMDs. Furthermore, based on the qgcomp model results, the combined association of perchlorate, nitrate, and thiocyanate exposure was negatively associated with BMDs (ß = -0.017, 95% CI: -0.041, -0.024 for total BMD; ß = -0.017, 95% CI: -0.029, -0.005 for lumbar BMD). Additionally, there was a significant effect after gender, age, and BMI stratification between perchlorate, nitrate, and thiocyanate with BMDs in the normal weight group (ß = -0.015, 95% CI: -0.020, -0.011 for total BMD; ß = -0.022, 95% CI: -0.028, -0.016 for lumbar BMD) and children and adolescents group (ß = -0.025, 95% CI: -0.031, -0.019 for total BMD; ß -0.017, 95% CI: -0.029, -0.005 for lumbar BMD). CONCLUSIONS: The present study indicated a negative correlation between BMDs and urinary perchlorate, nitrate, and thiocyanate levels, with nitrate being the main contributor to the mixture effect. People with normal weight and children and adolescents were more likely to be affected.

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Oral exposure to nanoparticles (NPs) may affect intestinal microbiota, and this effect may be further changed by co-contaminates. In the present study, we investigated the combined effects of TiO2 NPs and fipronil (FPN) on microbiota in mouse intestines. Mice were intragastric exposed to 5.74 mg/kg TiO2 NPs, 2.5 mg/kg FPN, or both of them, once a day, for 30 days. The results showed that individual exposure to TiO2 NPs or FPN decreased body weight and induced pathological changes in intestines. The exposure was also associated with increased cleaved caspase-3 protein, oxidative stress and decreased tight junction protein expression. Furthermore, the levels of diamine oxidase (DAO), lipopolysaccharide (LPS) and inflammatory cytokines in serum were also elevated, indicating increased intestinal barrier permeability. As expected, both TiO2 NPs and FPN decreased the diversity and altered the composition of microbiota. However, the observed effects were not further enhanced after the co-exposure to TiO2 NPs and FPN, except that Romboutsia was only significantly increased after the co-exposure to TiO2 NPs + FPN. We concluded that oral exposure to TiO2 NPs and FPN showed minimal synergistic effects on microbiota in mouse intestine.

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Food contaminates, such as insecticide, may influence the toxicity of nanoparticles (NPs) to intestine. The present study investigated the combined toxicity of TiO2 NPs and fipronil to male mouse intestine. Juvenile mice (8 weeks) were orally exposed to 5.74 mg/kg TiO2 NPs, 2.5 mg/kg fipronil, or both, once a day, for 5 days. We found that both TiO2 NPs and fipronil induced some pathological changes in intestines, accompanying with defective autophagy, but these effects were not obviously enhanced after TiO2 NP and fipronil co-exposure. Fipronil promoted Ti accumulation but induced minimal impact on other trace elements in TiO2 NP-exposed intestines. Metabolomics data revealed that the exposure altered metabolite profiles in mouse intestines, and two KEGG pathways, namely, ascorbate and aldarate metabolism (mmu00053) and glutathione metabolism (mmu00480), were only statistically significantly changed after TiO2 NP and fipronil co-exposure. Five metabolites, including 2-deoxy-D-erythro-pentofuranose 5-phosphate, 5alpha-cholestanol, beta-D-glucopyranuronic acid, elaidic acid, and isopentadecanoic acid, and maltotriose, were more significantly up-regulated after the co-exposure, whereas trisaccharide and xylonolactone were only significantly down-regulated by the co-exposure. We concluded that fipronil had minimal impact to enhance the toxicity of TiO2 NPs to mouse intestines but altered metabolite profiles.

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OBJECTIVES: The purpose of this study is to summarize the evidence for the association between snoring and hypertension and the effect of snoring on hypertension in men and/or women. METHODS: We searched the articles in the Cochrane Library, PubMed, Scopus, Web of Science and Embase published up to 12 November 2020 to evaluate the association between snoring and hypertension. Studies were selected according to the predefined screening criteria and their qualities were assessed by Newcastle-Ottawa Quality Evaluation Scale. The odds ratio and 95% confidence interval were used as effective indicators. It was registered in PROSPERO with the number: CRD42021224912. RESULTS: According to the inclusion/exclusion criteria, 11 studies including eight prospective cohort studies and three cross-sectional studies were included. The results showed that compared with non-snoring participants, snoring significantly increased the risk of hypertension in both men and women [odds ratio (OR) = 1.32, 95% confidence interval (CI), 1.23-1.42; men: odds ratio (OR) = 1.32; 95% confidence interval (CI), 1.18-1.49; women: odds ratio (OR) = 1.26; 95% confidence interval (CI), 1.14-1.40]. Besides, the risk of hypertension was significantly increased when the snoring frequency was ≥4 nights/week [frequency≥4 nights/week: odds ratio (OR) = 1.42; 95% confidence interval (CI), 1.21-1.66; 4 nights/week >frequency>0: odds ratio (OR) = 1.23; 95% confidence interval (CI),1.13-1.34]. CONCLUSIONS: Snoring is considered as an independent predictor of hypertension in both men and women, which may play a role in the prevention and control of hypertension. People who snore frequently should pay close attention to their blood pressure levels to prevent hypertension.

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OBJECTIVE: The purpose of this study is to evaluate the effects of combined aerobic and resistance exercise on blood pressure (BP) in postmenopausal women. The results of this study will provide an effective means for postmenopausal women to control BP and reduce the morbidity and mortality of cardiovascular disease (CVD). METHODS: Eligible studies were searched in five electronic databases until November 2020, and 11 randomized controlled trials that met the inclusion criteria were included in this systematic review and meta-analysis. The random-effects model was used to calculate overall effect sizes of weighted mean differences (WMD) and 95% confidence interval (CI). This study was registered in PROSPERO with the registration number: CRD42021225546. RESULTS: Compared with the control group, the aerobic combined resistance exercise significantly decreased the systolic blood pressure (SBP) and diastolic blood pressure (DBP) by 0.81 mmHg (95% CI, -1.34 to -0.28) and 0.62 mmHg (95% CI, -1.11 to -0.14), respectively. The results of the meta-analysis also indicated that a significant reduction in brachial-to-ankle pulse wave velocity (baPWV) of - 1.18 m/s (95% CI, -1.81 to -0.56) and heart rate (HR) of -0.22 beats/min (95% CI: -0.42 to -0.02) after combined aerobic and resistance exercise intervention. Subgroup analysis showed that postmenopausal women ≥60 years of age who were overweight or had a normal baseline BP were more sensitive to the combined aerobic and resistance exercise. When combined aerobic and resistance exercise frequency < 3 times/week, weekly exercise time ≥ 150 min, or the duration of exercise lasted for 12 weeks, the SBP and DBP of postmenopausal women could be reduced more effectively. CONCLUSIONS: The present study indicates that combined aerobic and resistance exercise can significantly reduce BP in postmenopausal women. Accordingly, combined aerobic and resistance exercise may be an effective way to prevent and manage hypertension in postmenopausal women.

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BACKGROUND: Previous clinical studies have shown controversial results regarding the effect of inorganic nitrate supplementation on blood pressure (BP) in older individuals. We performed this systematic review and meta-analysis to assess the effect of inorganic nitrate on BP in older adults. METHODS: Eligible studies were searched in Cochrane Library, PubMed, Scopus, Web of Science, and Embase. Randomized controlled trials which evaluated the effect of inorganic nitrate consumption on BP in older adults were recruited. The random-effect model was used to calculate the pooled effect sizes. RESULTS: 22 studies were included in this meta-analysis. Overall, inorganic nitrate consumption significantly reduced systolic blood pressure (SBP) by -3.90 mmHg (95% confidence interval: -5.23 to -2.57; P < 0.001) and diastolic blood pressure (DBP) by -2.62 mmHg (95% confidence interval: -3.86 to -1.37; P < 0.005) comparing with the control group. Subgroup analysis showed that the BP was significantly reduced when participants' age≥65, BMI>30, or baseline BP in prehypertension stage. And both SBP and DBP decreased significantly after acute nitrate supplementation of a single dose (<1 day) or more than 1-week. However, participants with hypertension at baseline were not associated with significant changes in both SBP and DBP. Subgroup analysis of measurement methods showed that only the resting BP group showed a significant reduction in SBP and DBP, compared with the 24-h ambulatory BP monitoring (ABPM) group and daily home BP measurement group. CONCLUSION: These results demonstrate that consuming inorganic nitrate can significantly reduce SBP and DBP in older adults, especially in whose age ≥ 65, BMI＞30, or baseline BP in prehypertension stage.

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OBJECTIVES: Previous clinical studies have shown controversial results regarding the effect of Lactobacillus supplementation on blood pressure (BP). The purpose of this systematic review and meta-analysis is to examine the effect of Lactobacillus consumption on BP. METHODS: Eligible randomized controlled trials (RCTs) were searched from five electronic databases until May 2020. In total, 18 studies were included in our meta-analysis. Quality of the selected studies was assessed, and a random-effects model was used to calculate the overall effect sizes of weighted mean differences (WMD). This systematic review was registered in PROSPERO with the number: CRD42019139294. RESULTS: Lactobacillus consumption significantly reduced systolic blood pressure (SBP) by -2.74 mmHg (95% confidence interval, -4.96 to -0.51) and diastolic blood pressure (DBP) by -1.50 mmHg (95% confidence interval, -2.44 to -0.56) when comparing with the control group. Subgroup analysis showed that type 2 diabetes mellitus (T2DM) patients, Asian individuals, or borderline hypertension participants were more sensitive to daily consumption of Lactobacillus. And the effect of Lactobacillus on BP-reduction was more significant in capsule form, with the dose was above 5 × 109 colony-forming unit (CFU)/day or lasted for more than 8 weeks. CONCLUSIONS: Our present study suggests that Lactobacillus consumption in capsule form when the daily dose is above 5 × 109 CFU for more than 8 weeks can decrease SBP or DBP in T2DM patients, borderline hypertension participants or Asian individuals.

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AIMS: Urea transporter B (UTB) is encoded by the SLC14α1 gene, and exerts its activity in the choroid plexus (CP) by regulating [Na+] in the cerebrospinal fluid (CSF) and maintaining normal blood pressure in mice fed on high salt diet. The aim of this study is to investigate the effect of high salt diet on the mean arterial pressure (MAP) in SLC14α1 depletion mice and its possible molecular mechanism. MAIN METHODS: Adult male mice were divided into four groups: 1) UTB+/+(wild type) mice + normal salt diet (0.3% NaCl, NS); 2) UTB+/+ mice + high salt diet (8% NaCl, HS); 3) UTB-/- (SLC14α1 knockout) mice + NS; 4) UTB-/- mice + HS, each group consisted of 6 mice. The MAP of mice was measured by non-invasive detection method after HS diet for 4 weeks, followed by euthanization for brain and blood collection. KEY FINDINGS: HS significantly elevated the MAP and CSF [Na+] in UTB-/- mice in comparison with wild type mice; however, NS didn't alter the MAP and CSF [Na+] in either wild type mice or UTB-/- mice. HS also induced the expression of ENaC-α and α1-Na+-K+-ATPase in UTB-/- mice as confirmed by RT-PCR and Western blot. SIGNIFICANCE: These results suggest that the depletion of SLC14α1 gene in mice may contribute to the HS-induced abnormality of sodium transportation in the CSF, and lead to the elevation of MAP, which eventually promote the development of salt-sensitive hypertension.

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