Early-life tobacco smoke elevating later-life osteoporosis risk: Mediated by telomere length and interplayed with genetic predisposition.

INTRODUCTION: The growing prevalence of osteoporosis (OP) in an aging global population presents a significant public health concern. Tobacco smoke negatively affects bone turnover, leading to reduced bone mass and heightened OP and fracture risk. However, the impact of early-life tobacco smoke exposure on later-life OP risk remains unclear. OBJECTIVES: This study was to explore the effects of early-life tobacco smoke exposure on incident OP risk in later life. The mediating role of telomere length (TL) and the interaction with genetic predisposition were also studied. METHODS: Data on in utero tobacco smoke exposure (IUTSE) status and age of tobacco use initiation from the UK Biobank were used to estimate early-life tobacco smoke exposure. Incident OP cases were identified according to health-related records. Linear, Cox, and Laplace regression models were mainly used for data analysis. RESULTS: Individuals with IUTSE showed a higher OP risk [hazard ratio (HR): 1.06, 95 % confidence interval (CI): 1.01, 1.11] and experienced earlier OP onset by 0.30 years [50th percentile difference = -0.30, 95 % CI: -0.51, -0.09] compared to those without. Participants initiating tobacco smoke in childhood, adolescence, and adulthood had 1.41 times (95 % CI: 1.23, 1.61), 1.17 times (95 % CI:1.10, 1.24), and 1.14 times (95 % CI: 1.07, 1.20) the risk of OP, respectively, compared to never smokers. They also experienced earlier OP onset by 2.16, 0.95, and 0.71 years, sequentially. The TL significantly mediated the early-life tobacco exposure and OP association. Significant joint and interactive effects were detected between early-life tobacco smoke exposure and genetic elements. CONCLUSIONS: Our findings implicate that early-life tobacco smoke exposure elevates the later-life OP risk, mediated by telomere length and interplayed with genetic predisposition. These findings highlight the importance of early-life intervention against tobacco smoke exposure and ageing status for precise OP prevention, especially in individuals with a high genetic risk.

Frailty phenotype as mediator between systemic inflammation and osteoporosis and fracture risks: A prospective study.

BACKGROUND: Systemic inflammation and frailty have been implicated in osteoporosis (OP) and fracture risks; however, existing evidence remains limited and inconclusive. This study aimed to assess the associations of systemic inflammation and frailty phenotype with incident OP and fracture and to evaluate the mediating role of frailty phenotype. METHODS: The present study analysed data from the UK Biobank, a comprehensive and representative dataset encompassing over 500 000 individuals from the general population. Baseline peripheral blood cell counts were employed to calculate the systemic inflammation markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII). Frailty phenotype was assessed using five criteria, defined as frail (≥3 items met), pre-frail (1-2 items met) and non-frail (0 items met). OP and fracture events were confirmed through participants' health-related records. Multivariable linear and Cox regression models were utilized, along with mediation analysis. RESULTS: Increased systemic inflammation was associated with increased risks of OP and fracture. The corresponding hazard ratios and 95% confidence intervals (CIs) for OP risk per standard deviation increase in the log-transformed NLR, PLR and SII were 1.113 (1.093-1.132), 1.098 (1.079-1.118) and 1.092 (1.073-1.111), and for fracture risk, they were 1.066 (1.051-1.082), 1.059 (1.044-1.075) and 1.073 (1.058-1.089), respectively. Compared with the non-frail individuals, the pre-frail and frail ones showed an elevated OP risk by 21.2% (95% CI: 16.5-26.2%) and 111.0% (95% CI: 98.1-124.8%), respectively, and an elevated fracture risk by 6.1% (95% CI: 2.8-9.5%) and 38.2% (95% CI: 30.7-46.2%), respectively. The systemic inflammation level demonstrated a positive association with frailty, with ß (95% CI) of 0.034 (0.031-0.037), 0.026 (0.023-0.029) and 0.008 (0.005-0.011) in response to per standard deviation increment in log-transformed SII, NLR and PLR, respectively. The frailty phenotype mediated the association between systemic inflammation and OP/fracture risk. Subgroup and sensitivity analyses confirmed the robustness of these findings. CONCLUSIONS: Systemic inflammation and frailty phenotype are independently linked to increased risks of OP and fracture. The frailty phenotype partially mediates the association between systemic inflammation and osteoporotic traits. These results highlight the significance of interventions targeting systemic inflammation and frailty in OP and fracture prevention and management.

Real-time detection of acetone gas molecules at ppt levels in an air atmosphere using a partially suspended graphene surface acoustic wave skin gas sensor.

To improve the quality of modern life in the current society, low-power, highly sensitive, and reliable healthcare technology is necessary to monitor human health in real-time. In this study, we fabricated partially suspended monolayer graphene surface acoustic wave gas sensors (G-SAWs) with a love-mode wave to effectively detect ppt-level acetone gas molecules at room temperature. The sputtered SiO2 thin film on the surface of a black 36°YX-LiTaO3 (B-LT) substrate acted as a guiding layer, effectively reducing the noise and insertion loss. The G-SAWs exhibited enhanced gas response towards acetone gas molecules (800 ppt) in a real-time atmosphere. The high sensitivity of the G-SAW sensor can be attributed to the elasticity and surface roughness of the SiO2 film. In addition, the G-SAW sensor exhibited rapid response and recovery at room temperature. This study provides a potential strategy for diagnosing different stages of diabetes in the human body.

Isolation and Characterization of Bacteriophage VA5 against Vibrio alginolyticus.

Bacteriophages, or phages, can be used as natural biological control agents to eliminate pathogenic bacteria during aquatic product cultivation. Samples were collected from seafood aquaculture water and aquaculture environmental sewage, and phage VA5 was isolated using the double-layer agar plate method, with Vibrio alginolyticus as the host bacteria. The purified phage strain was subjected to genome sequencing analysis and morphological observation. The optimal multiplicity of infection (MOI), the one-step growth curve, temperature stability, and pH stability were analyzed. Phage VA5 was observed to have a long tail. Whole-genome sequencing revealed that the genome was circular dsDNA, with 35,866 bp length and 46% G+C content. The optimal MOI was 1, the incubation period was 20 min, the outbreak period was 30 min, and the cleavage amount was 92.26 PFU/cell. The phage showed good activity at -20 °C, 70 °C, and pH 2-10. Moreover, the phage VA5 exhibited significant inhibitory effects on V. alginolyticus-infected shrimp culture. The isolated phage VA5 has a wide range of host bacteria and is a good candidate for biological control of pathogenic bacteria.

Molecular Sieving of Propyne/Propylene by a Scalable Nanoporous Crystal with Confined Rotational Shutters.

Soft porous coordination polymers (PCPs) have the remarkable ability to recognize similar molecules as a result of their structural dynamics. However, their guest-induced gate-opening behaviors often lead to issues with selectivity and separation efficiency, as co-adsorption is nearly unavoidable. Herein, we report a strategy of a confined-rotational shutter, in which the rotation of pyridyl rings within the confined nanospace of a halogen-bonded coordination framework (NTU-88) creates a maximum aperture of 4.4 Å, which is very close to the molecular size of propyne (C3 H4 : 4.4 Å), but smaller than that of propylene (C3 H6 : 5.4 Å). This has been evidenced by crystallographic analyses and modelling calculations. The NTU-88o (open phase of activated NTU-88) demonstrates dedicated C3 H4 adsorption, and thereby leads to a sieving separation of C3 H4 /C3 H6 under ambient conditions. The integrated nature of high uptake ratio, considerable capacity, scalable synthesis, and good stability make NTU-88 a promising candidate for the feasible removal of C3 H4 from C3 H4 /C3 H6 mixtures. In principle, this strategy holds high potential for extension to soft families, making it a powerful tool for optimizing materials that can tackle challenging separations with no co-adsorption, while retaining the crucial aspect of high capacity.

Potential roles of gut microbiota in metal mixture and bone mineral density and osteoporosis risk association: an epidemiologic study in Wuhan.

Few studies have focused on the effects of multiple metal mixtures on bone health and the underlying mechanisms related to alterations in the gut microbiota. This study aimed to examine the potential roles of gut microbiota alterations in metal mixtures and their association with osteoporosis traits. Adults aged ≥ 55 years were recruited from two community healthcare centers in Wuhan City during 2016-2019. The plasma concentrations of six metals (zinc, iron, selenium, lead, cadmium, and arsenic) were measured using an inductively coupled plasma mass spectrometer. The k-means clustering method was employed to explore the exposure profiles of metal mixtures for all participants. 16S rRNA gene sequencing was used to profile the gut microbiota of participants. Combining these results with those of our previous study, we identified overlapping taxa and evaluated their potential roles. A total of 806 participants (516 females), with an average age of 67.36 years were included. The participants were grouped into three clusters using k-means clustering: Cluster 1 (n = 458), Cluster 2 (n = 199), and Cluster 3 (n = 149). The high-exposure group for iron, zinc, lead, and cadmium (Cluster 3) showed a negative association with lumbar spine 1-4 bone mineral density (BMD). A total of 201 individuals (121 females) underwent sequencing of the gut microbiota. Both alpha and beta diversities were statistically different among the three groups. Bacteroidaceae, Lachnospiraceae, Bifidobacteriaceae, Bacteroides, and Lachnospiraceae_incertae_sedis were identified as overlapping taxa associated with the metal mixtures and BMD. Interaction analysis revealed that Cluster 3 interacted with Bacteroidaceae/Bacteroides, resulting in a positive effect on LS1-4 BMD (ß = 0.358 g/cm2, 95% CI: 0.047 to 0.669, P = 0.025). Our findings indicate associations between multiple metal mixtures and BMD as well as gut microbiota alterations. Exploring the interaction between metal mixtures and the gut microbiota provides new perspectives for the precise prevention and treatment of osteoporosis.

Role of lifestyle factors in mediating the effect of educational attainment on bone mineral density: a Mendelian randomization study.

We performed two-step multivariable Mendelian randomization analysis to explore the mediating role of lifestyle factors in educational attainment (EA) and bone mineral density (BMD). Summary statistics from genome-wide association studies of European lineages were used. Coffee intake and processed-meat intake mediated the association between EA and BMD. PURPOSE: This study aimed to explore the causal relationship between educational attainment (EA) and bone mineral density (BMD), as well as the potential mediating roles of lifestyle factors in the expected EA-BMD relationship. By identifying modifiable lifestyle factors, we hope to provide relevant information to prevent osteoporosis or low BMD in the less educated population. METHODS: Using summary statistics from genome-wide association studies (GWAS) of major European lineages, one- and two-sample Mendelian randomization (MR) analyses were performed to estimate the association between EA (in the social sciences genetic association consortium (SSGAC) involving 766,345 individuals and in the UK Biobank (UKB) involving 293,723 individuals) and BMD (in the Genetic Factors for Osteoporosis Consortium involving 426,824 individuals selected from the UKB). The EA variable in both consortia were expressed by years of schooling completed. Two-step multivariable MR was used to assess the mediating roles of eight lifestyle-related factors (moderate-to-vigorous physical activity, watching television, computer using, smoking initiation, coffee intake, alcohol intake frequency, tea intake, and processed-meat intake) in the EA and BMD association, and the corresponding mediating proportion was calculated. Meta-analysis was used to present a pooled estimate. RESULTS: A total of 317 and 73 independent single-nucleotide polymorphisms (SNPs) of GWAS significance (P < 5.0 × 10-8) were selected as instrumental variables (IVs) for EA in the SSGAC and UKB, respectively. A total of 513 SNPs were selected as IVs for the BMD. The results of one- and two-sample MR revealed that the genetically predicted BMD increased by 0.094 and 0.047 g/cm2, respectively, in response to each SD increment of genetically predicted schooling years. Among the eight candidate mediators, coffee intake and processed-meat intake were potential mediators revealed by the two-step multivariable MR analysis, mediating 26.87% and 23.92% of EA's effect on BMD, respectively. Meta-analysis showed consistent findings. Results of sensitivity analysis indicated the robustness of our findings. CONCLUSION: We elucidated the causal protective effect of EA on BMD and the mediating roles of coffee intake and processed-meat intake. Intervening with these factors can potentially reduce the burden of bone density loss or osteoporotic fractures among the less educated population.

Mediating role of host metabolites in strontium's effect on osteoporosis among older individuals: Findings from Wuhan, China.

Strontium is receiving widespread attention due to its remarkable biological qualities in preventing bone resorption and fostering osteogenesis. However, the chemical processes behind strontium's dual activities on bone cells are not yet fully understood. This study used the metabolomic technique to identify and examine potential biomarkers between strontium exposure and osteoporosis (OP) risk. A total of 806 participants were recruited for the detection of plasma strontium content via inductively coupled plasma-mass spectrometry. Plasma metabolites were profiled in 254 participants through an untargeted metabolomics technique. Generalized linear models were primarily used to analyze associations among plasma strontium, metabolites, and OP. The mediating effects of metabolites on the strontium-OP association were further investigated. A total of 31 differential metabolites were observed, 10 of which were upregulated and 21 were downregulated in the OP group compared with the non-OP group. Five metabolites (3-phenoxybenzoic acid, Cer (t18:0/16:1), HexCer(t16:1/12:1(2OH)), HexCer(t14:2/18:1(2OH)), and TG(16:0-18:1-24:4)) were selected as potential mediators based on their significant association with OP risk and with femoral neck and lumbar spine bone mineral density (BMD). Moreover, all except TG(16:0-18:1-24:4) were involved in the OP discrimination model with excellent power combined with several traditional variables. 3-Phenoxybenzoic acid and Cer(t18:0/16:1) had significant indirect effects on the strontium-OP association. The five candidate metabolites mediated 83.79 % of the strontium-OP association. Plasma strontium level was associated with reduced OP risk in the Han population in Wuhan. Thus, plasma metabolite profiling revealed five BMD/OP-associated metabolites that acted as mediators in the strontium-OP association. Our findings provided evidence of the mediating role of host plasma metabolites in strontium's effect on OP pathology.

Metal mixture and osteoporosis risk: Insights from plasma metabolite profiling.

The pathophysiology of osteoporosis (OP) is influenced by exposure to nonessential harmful metals and insufficient or excessive intake of necessary metals. Investigating multiple plasma metals, metabolites, and OP risk among older adults may reveal novel clues of underlying mechanisms for metal toxicity on bone mass. A total of 294 adults ≥ 55 years from Wuhan communities were included. Plasma concentrations of 23 metals and metabolites were measured via inductively coupled plasma-mass spectrometry and global metabolite detection. To investigate the relationships between plasma metals, OP risk, and OP-related metabolites, three different statistical techniques were used: generalized linear regression model, two-way orthogonal partial least-squares analysis (O2PLS), and weighted quantile sum (WQS). The mean ages were 66.82 and 66.21 years in OP (n = 115) and non-OP (n = 179) groups, respectively. Of all 2999 metabolites detected, 111 differential between-group members were observed. The OP risk decreased by 58.5% (OR=0.415, 95% CI: 0.237, 0.727) per quartile increment in the WQS index indicative of metal mixture exposure. Consistency remained for bone mineral density (BMD) measurements. The O2PLS model identified the top five OP-related metabolites, namely, DG(18:2_22:6), 3-phenoxybenzoic acid, TG(16:1_16:1_22:6), TG(16:0_16:0_20:4), and TG(14:1_18:2_18:3), contributing most to the joint covariation between the metal mixture and metabolites. Significant correlations between each of them and the metal mixture were found using WQS regression. Furthermore, the five metabolites mediated the associations of the metal mixtures, BMD, and OP risk. Our findings shed additional light on the mediation functions of plasma metabolites in the connection between multiple metal co-exposure and OP pathogenesis and offer new insights into the probable mechanisms underpinning the bone effects of the metal mixture.

Joint effects of phenol, chlorophenol pesticide, phthalate, and polycyclic aromatic hydrocarbon on bone mineral density: comparison of four statistical models.

Exposure to phenols, phthalates, pesticides, and polycyclic aromatic hydrocarbons (PAHs) can harm the skeleton. However, data about the joint effects of these chemicals' mixture on bone health are limited. The final analysis involved 6766 participants aged over 20 years recruited from the National Health and Nutrition Examination Survey. Generalized linear regression, weighted quantile sum (WQS) regression, Bayesian kernel machine regression (BKMR), and quantile g-computation (qgcomp) were performed to investigate the association of the urinary levels of chemicals (three phenols, two chlorophenol pesticides, nine phthalates, and six polycyclic aromatic hydrocarbon [PAH] metabolites) with bone mineral density (BMD) measurements and osteoporosis (OP) risk. Generalized linear regression identified that benzophenone-3, 2,4-dichlorophenol, mono-n-butyl phthalate, 1-napthol, 3-fluorene, 2-fluorene, and 1-phenanthrene were significantly associated with lower BMD and increased OP risk. The WQS index was negatively associated with total femur, femoral neck, and lumbar spine vertebra 1 (L1) BMD among all the participants, with corresponding ß (95% confidence interval) values of -0.028 g/cm2 (-0.040, -0.017), -0.015 g/cm2 (-0.025, -0.004), and -0.018 g/cm2 (-0.033, -0.003). In the BKMR analysis, the overall effect of the mixture was significantly associated with femoral neck BMD among males and OP risk among females. The qgcomp model found a significant association between co-exposure and L1 BMD among all the participants and among males. Our study presents compelling epidemiological evidence that co-exposure to phenols, chlorophenol pesticides, phthalates, and PAHs is associated with reduced BMD and elevated OP risk. It provides epidemiologic evidence for the detrimental effects of these chemicals on bone health.

Exposure to phenols, chlorophenol pesticides, phthalate and PAHs and mortality risk: A prospective study based on 6 rounds of NHANES.

OBJECTIVES: Human exposure to various endocrine disrupting chemicals (EDCs) is widespread and long-lasting. The primary objective of this study was to prospectively evaluate the association of combined exposure of phenols, chlorophenol pesticides, phthalate and polycyclic aromatic hydrocarbons (PAHs) and mortality risk in a representative US population. METHODS: The data on urinary levels of phenols, chlorophenol pesticides, phthalates, and PAH metabolites, were collected from participants aged ≥20 years in six rounds of the National Health and Nutrition Examination Survey (NHANES) (2003-2014). NHANES-linked death records up to December 31, 2015 were used to ascertain mortality status and cause of death. Cox proportional hazards and competing risk models were mainly used for chemical and mortality risk association analysis. The weighted quantile sum (WQS) regression and the least absolute shrinkage and selection operator regression were employed to estimate the association between EDC co-exposure and mortality risk. RESULTS: High levels of mono-n-butyl phthalate, monobenzyl phthalate, and 1-napthol were significantly associated with increased risk of all cause, cardiovascular disease (CVD) and cancer mortality among all participants. WQS index was associated with the risks of all-cause (hazard ratio [HR] = 1.389, 95%CI: 1.155-1.669) and CVD mortality (HR = 1.925, 95%CI: 1.152-3.216). High co-exposure scores were associated with elevated all-cause (HR = 2.842, 95% CI: 1.2.094-3.858), CVD (HR = 1.855, 95% CI: 1.525-2.255), and cancer mortality risks (HR = 2.961, 95% CI: 1.468-5.972). The results of subgroup analysis, competing risk model, and sensitivity analysis were generally consistent with the findings from the main analyses, indicating the robustness of our findings. CONCLUSIONS: This study provided the first epidemiological evidence that co-exposure to EDC at fairly low levels contributed to elevated mortality risk among US adults. The underlying mechanisms for the effects of EDC co-exposure on human health are worthy of future exploration.

Composite dietary antioxidant intake and osteoporosis likelihood in premenopausal and postmenopausal women: a population-based study in the United States.

OBJECTIVE: Osteoporosis is a skeletal disease characterized by low bone mass, reduced bone strength, and increased fracture risk. We aimed to investigate the association between combined dietary antioxidant intake and the likelihood of osteoporosis in premenopausal and postmenopausal women, based on data from the National Health and Nutrition Examination Survey. METHODS: Nutrient intake data were obtained using two 24-hour recalls. Composite dietary antioxidant index (CDAI), which refers to the intake amounts of ß-carotene, vitamin A, vitamin C, vitamin E, selenium, zinc, copper, and iron, was then constructed. Prevalent osteoporosis was defined according to bone mineral density T scores of ≤ -2.5 and self-reports. Multiple logistic and Poisson regression models were used for association analyses. RESULTS: A total of 3,418 participants (1,157 premenopausal and 2,261 postmenopausal women) 40 years or older were included, 776 (22.70%) of whom had prevalent osteoporosis. In terms of individual nutrients, postmenopausal women in the highest CDAI quartiles for dietary ß-carotene, vitamin A, vitamin C, and iron intakes had a low likelihood of osteoporosis. Regarding the CDAI-osteoporosis association, postmenopausal women in the highest quartile were less likely to have osteoporosis (OR Q3 vs Q1 , 0.64; 95% CI, 0.43-0.96; OR Q4 vs Q1 , 0.56; 95% CI, 0.35-0.89; P for trend = 0.013), after controlling for covariates. CONCLUSIONS: CDAI was negatively associated with the likelihood of osteoporosis in postmenopausal women. Our findings suggest that the combined intake of antioxidant nutrients can help reduce the likelihood of osteoporosis in women.

Association between multiple vitamins and bone mineral density: a cross-sectional and population-based study in the NHANES from 2005 to 2006.

BACKGROUND: Bone mineral density (BMD) alterations in response to multivitamin exposure were rarely studied. Our study assessed the association of coexposure to six types of vitamins (i.e., vitamins B12, B9, C, D, A and E) with BMD measurements in adults in the US. METHODS: Data were collected from participants aged ≥ 20 years (n = 2757) in the U.S. National Health and Nutrition Examination Surveys (NHANES) from 2005 to 2006. Multiple linear regression, restricted cubic splines, principal component analysis (PCA) and weighted quantile sum (WQS) regression were performed for statistical analysis. RESULTS: The circulating levels of vitamins B12 and C were positively associated with BMDs, and an inverted L-shaped exposure relationship was observed between serum vitamin C and BMDs. PCA identified two principal components: one for 'water-soluble vitamins', including vitamins B12, B9 and C, and one for 'fat-soluble vitamins', including vitamins A, D and E. The former was positively associated with total femur (ß = 0.009, 95%CI: 0.004, 0.015) and femoral neck (ß = 0.007, 95%CI: 0.002, 0.013) BMDs, and the latter was negatively associated with BMDs with non-statistical significance. The WQS index constructed for the six vitamins was significantly related to total femur (ß = 0.010, 95%CI: 0.001, 0.018) and femoral neck (ß = 0.008, 95%CI: 0.001, 0.015) BMDs, and vitamins B12 and C weighted the most. The WQS index was inversely related to BMDs with non-statistical significance, and vitamins E and A weighted the most. CONCLUSION: Our findings suggested a positive association between water-soluble vitamin coexposure and BMD, and the association was mainly driven by vitamins B12 and C. Negative association between fat-soluble vitamin coexposure and BMD was indicated, mainly driven by vitamins E and A. An inverted L-shaped exposure relationship was found between vitamin C and BMD.

Facile Solution-Refluxing Synthesis and Photocatalytic Dye Degradation of a Dynamic Covalent Organic Framework.

Covalent organic frameworks (COFs), as a novel crystalline porous adsorbent, have been attracting significant attention for their synthesis and application exploration due to the advantages of designability, stability, and functionalization. Herein, through increasing the concentration of the acid catalyst, a facile solution-refluxing synthesis method was developed for the preparation of a three-dimensional dynamic COF material, COF-300, with high yields (>90%) and high space−time yields (>28 kg m−3 day−1). This synthesis method not only permits gram-scale synthesis, but also yields products that well maintain porosity and unique guest-dependent dynamic behavior. Moreover, the catalytic activity of COF-300 as a metal-free photocatalyst was explored for the first time. Under 365 nm ultra-violet light irradiation, COF-300 can effectively catalyze the dye degradation (>99%) in wastewater with good recyclability. By adding magnetic Fe3O4 nanoparticles into the solution-refluxing synthesis of COF-300, Fe3O4/COF-300 nanocomposites can be obtained and used as magnetically recyclable photocatalysts, demonstrating the superiority of this facile synthesis procedure. Our study provides new insights for the preparation of COF materials and a constructive exploration for their water treatment application.

Association between SEMA3A signaling pathway genes and BMD/OP risk: An epidemiological and experimental study.

Objective: This study aimed to explore the associations of genetic variants in the semaphorin 3A (SEMA3A) signaling pathway genes, including SEMA3A, NRP1, PLXNA1, PLXNA2 and PLXNA3 with osteoporosis (OP) risk and bone mineral density (BMD) in a Chinese Han older adult population. Study design and method: A two-stage design was adopted. Total of 47.8kb regions in the 5 genes were sequenced using targeted next-generation sequencing (NGS) technology in the discovery stage, and the discovered OP-related single nucleotide polymorphisms (SNPs) were further genotyped using improved multiple linkage detection reaction technique in the validation stage. Methods of ALP/TRAP staining, real-time fluorescent quantitative PCR, and cell proliferation and apoptosis assays were performed with MC3T3-E1 and RAW 264.7 cell lines to clarify biological effects of observed functional variants in cell lines responsible for bone mass remodeling. Results: Total of 400 postmenopausal women (211 OP cases) were involved in the discovery stage, where 6 common and 4 rare genetic variants were found to be associated with OP risk. In the validation stage among another 859 participants (417 women, 270 OP cases), the PLXNA2 rs2274446 T allele was associated with reduced OP risk and increased femoral neck (FN) BMD compared to the C allele. Moreover, significant associations of NRP1 rs2070296 with FN BMD/OP risk and of NRP1 rs180868035 with lumbar spine and FN BMDs were also observed in the combination dataset analysis. Compared to the osteoblasts/osteoclasts transfected with the wild-type NRP1 rs180868035, those transfected with the mutant-type had reduced mRNA expression of osteoblastic genes (i.e., ALP, RUNX2, SP7 and OCN), while elevated mRNA expression of osteoclastic genes (i.e., TRAP, NFATc1 and CTSK). Furthermore, mutant NRP1 rs180868035 transfection inhibited osteoblast proliferation and osteoclast apoptosis, while promoted osteoclast proliferation and osteoblast apoptosis in corresponding cell lines. Conclusion: Genetic variants located in NRP1 and PLXNA2 genes were associated with OP risk and BMD. The NRP1 rs180868035 affects bone metabolism by influencing osteoblasts and osteoclasts differentiation, proliferation and apoptosis.

Association of volatile organic compounds co-exposure with bone health indicators and potential mediators.

Limited evidence was found in the associations of volatile organic compound (VOC) exposure with bone health indicators. This study aimed to explore the associations of individual and combined metabolites of VOCs (mVOCs) in urine, a representative of the internal exposure level of VOCs, with bone mineral density (BMD), osteoporosis (OP) and fracture, and potential mediators. Data of the National Health Examination and Nutrition Survey 2005-2006 and 2013-2014 was used. Multiple linear and logistic regression modeling were performed to analyze the associations of individual mVOC with bone health indicators. The least absolute shrinkage and selection operator (LASSO) regression was adopted to select mVOCs that were more relevant to bone health indicators for further weight quantile sum (WQS) analysis used for analyzing the associations between multiple VOC co-exposure and bone health indicators. Mediation analysis was used to identify potential mediators. Seventeen mVOC members with detection rate of >50% in urine of all 3478 participants aged ≥20 years (1829 females) were involved. Levels of most mVOCs were higher in women than men. Eight mVOCs were negatively associated with BMDs, and two and four mVOCs were positively associated with OP and fracture risks, respectively. WQS regression revealed decreased femoral neck BMD (ß = -0.010 g/cm2, 95% CI: -0.020, -0.0001) and total spine BMD (ß = -0.015 g/cm2, 95% CI: -0.028, -0.002) in response to increasing mVOC mixture levels. And alkaline phosphatase (ALP), body mass index (BMI), fasting insulin (FI) and high-density lipoprotein (HDL), were mediators in the associations with proportions of mediating effect ranging from 4.6% to 10.2%. Individual and combined VOC (co-)exposure were associated with reduced BMDs in American adults. ALP, BMI, FI and HDL were demonstrated to be mediators in the association of multiple VOC co-exposure with BMD.

An evaluation index system for regional mobile SARS-CoV-2 virus nucleic acid testing capacity in China: a modified Delphi consensus study.

BACKGROUND: Large-scale detection has great potential to bring benefits for containing the COVID-19 epidemic and supporting the government in reopening economic activities. Evaluating the true regional mobile severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus nucleic acid testing capacity is essential to improve the overall fighting performance against this epidemic and maintain economic development. However, such a tool is not available in this issue. We aimed to establish an evaluation index system for assessing the regional mobile SARS-CoV-2 virus nucleic acid testing capacity and provide suggestions for improving the capacity level. METHODS: The initial version of the evaluation index system was identified based on massive literature and expert interviews. The Delphi method questionnaire was designed and 30 experts were consulted in two rounds of questionnaire to select and revise indexes at all three levels. The Analytic Hierarchy Process method was used to calculate the weight of indexes at all three levels. RESULTS: The evaluation index system for assessing the regional mobile SARS-CoV-2 virus nucleic acid testing capacity, including 5 first-level indexes, 17 second-level indexes, and 90 third-level indexes. The response rates of questionnaires delivered in the two rounds of consultation were 100 and 96.7%. Furthermore, the authority coefficient of 30 experts was 0.71. Kendall's coordination coefficient differences were statistically significant (P < 0.001). The weighted values of capacity indexes were established at all levels according to the consistency test, demonstrating that 'Personnel team construction' (0.2046) came first amongst the five first-level indexes, followed by 'Laboratory performance building and maintenance' (0.2023), 'Emergency response guarantee' (0.1989), 'Information management system for nucleic acid testing resources' (0.1982) and 'Regional mobile nucleic acid testing emergency response system construction' (0.1959). CONCLUSION: The evaluation system for assessing the regional mobile SARS-CoV-2 virus nucleic acid testing capacity puts forward a specific, objective, and quantifiable evaluation criterion. The evaluation system can act as a tool for diversified subjects to find the weak links and loopholes. It also provides a measurable basis for authorities to improve nucleic acid testing capabilities.

Ligand Tailoring Strategy of a Metal-Organic Framework for Optimizing Methane Storage Working Capacities.

Methane, as the main component of natural gas, shale gas, and marsh gas, is regarded as an ideal clean energy to replace traditional fossil fuels and reduce carbon emissions. Porous materials with superior methane storage capacities are the key to the wide application of adsorbed natural gas technology in vehicle transportation. In this work, we applied a ligand tailoring strategy to a metal-organic framework (NOTT-101) to fine-tune its pore geometry, which was well characterized by gas and dye sorption measurements. High-pressure methane sorption isotherms revealed that the methane storage performance of the modified NOTT-101 can be effectively improved by decreasing the unusable uptake at 5 bar and increasing the total uptake under high pressures, achieving a substantially high volumetric methane storage working capacity of 190 cm3 (STP) cm-3 at 298 K and 5-80 bar.

Manganese, iron, copper, and selenium co-exposure and osteoporosis risk in Chinese adults.

BACKGROUND & AIMS: Previous experimental studies demonstrated that either deficient or excessive trace elements, such as manganese (Mn), iron (Fe), copper (Cu) and selenium (Se), are detrimental to bone health. Epidemiologic evidence for the effect of the four trace elements on osteoporosis (OP) risk remains inadequate. This cross-sectional study aimed to examine their associations with the OP risk among Chinese adults. METHODS: Concentrations of Mn, Fe, Cu, and Se were measured in plasma using an inductively coupled plasma mass spectrometer among 627 Chinese adults aged ≥ 50 years. Individual effect of the four elements on OP risk was analyzed by logistic regression and Bayesian Kernel Machine Regression (BKMR) models. The latter model was also adopted to examine the exposure-response relationships and joint effects of the four elements on OP risk. RESULTS: The median Mn, Fe, Cu, and Se levels were 4.78, 1026.63, 904.55, and 105.39 µg/L, respectively, in all participants. Inverse associations of Fe and Se levels with OP risk were observed in the logistic regression model. BKMR analysis revealed a U-shape pattern for the Fe-OP association, and a reduced OP risk in response to co-exposure of the four elements above the 50th percentiles but an elevated one in response to that below the 50th percentiles. Sex discrepancy existed in the findings. No interactions were found for the four elements affecting OP risk. CONCLUSIONS: Co-exposure to Mn, Fe, Cu, and Se was associated with improved bone density, where Fe contributed most to the beneficial effect. Further studies are needed to verify these findings and explore the underlying biological mechanism.

Association Between Water Intake and Mortality Risk-Evidence From a National Prospective Study.

Background: Few studies have explored the association between water intake and mortality risk, and the findings were inconsistent. Objective: This study aimed to explore the water intake-mortality association, utilizing the data from the National Health and Nutrition Examination Survey (NHANES) and the 2015 public-linked mortality files released by the National Center for Health Statistics. Methods: We used the diet- and mortality-linked data of a total of 35,463 adults (17,234 men) aged ≥20 years in the NHANESs 1999-2014 to perform a prospective study. The multivariate-adjusted Cox proportional hazards model was used to explore the associations of the amount of water intake (expressed by total water, plain water, beverage, and food water) and water intake proportion (expressed by the percentage of each kind of water) with mortality risks due to all causes, malignant neoplasms/cancer, and heart disease. The restricted cubic spline plots were adopted to clarify the dose-response relationships among them. Results: With a median of 88 months (interquartile range: 49-136 months) follow-up, a total of 4,915 all-cause deaths occurred, including 1,073 and 861 deaths from malignant neoplasms/cancer and heart disease, respectively. The amount of water intake in either type was negatively associated with all-cause mortality risk. Additionally, the negative linear dose-response relationships of water intake and all-cause mortality risk were found for all types of water except for food water, which followed a non-linear pattern. Similarly, compared to the lowest quartile (beverage water intake: <676 g/day; food water intake: <532 g/day), beverage and food water intakes in the range of 1,033-1,524 and 1,612-3,802 g/day were associated with decreased malignant neoplasms/cancer mortality risk. A U-shaped dose-response relationship was found for beverage water intake and malignant neoplasms/cancer mortality risk and a negative linear dose-response relationship was found for food water intake and malignant neoplasms/cancer mortality risk. Coffee and/or tea consumption was/were negatively associated with mortality risks due to all causes and malignant neoplasms/cancer. No significant associations of water intake proportion and mortality risks were found. Conclusion: Our findings demonstrated that higher water intake is associated with lower mortality risks among the United States population.