Associations of Heavy Metals with Cognitive Function: An Epigenome-Wide View of DNA Methylation and Mediation Analysis.

OBJECTIVE: Exposure to heavy metals has been reported to be associated with impaired cognitive function, but the underlying mechanisms remain unclear. This pilot study aimed to identify key heavy metal elements associated with cognitive function and further explore the potential mediating role of metal-related DNA methylation. METHODS: Blood levels of arsenic, cadmium, lead, copper, manganese, and zinc and genome-wide DNA methylations were separately detected in peripheral blood in 155 older adults. Cognitive function was evaluated using the Mini-Mental State Examination (MMSE). Least absolute shrinkage and selection operator penalized regression and Bayesian kernel machine regression were used to identify metals associated with cognitive function. An epigenome-wide association study examined the DNA methylation profile of the identified metal, and mediation analysis investigated its mediating role. RESULTS: The MMSE scores showed a significant decrease of 1.61 (95% confidence interval [CI]: -2.64, -0.59) with each 1 standard deviation increase in ln-transformed arsenic level; this association was significant in multiple-metal models and dominated the overall negative effect of 6 heavy metal mixture on cognitive function. Seventy-three differentially methylated positions were associated with blood arsenic (p < 1.0 × 10-5). The methylation levels at cg05226051 (annotated to TDRD3) and cg18886932 (annotated to GAL3ST3) mediated 24.8% and 25.5% of the association between blood arsenic and cognitive function, respectively (all p < 0.05). INTERPRETATION: Blood arsenic levels displayed a negative association with the cognitive function of older adults. This finding shows that arsenic-related DNA methylation alterations are critical partial mediators that may serve as potential biomarkers for further mechanism-related studies. ANN NEUROL 2024;96:87-98.

The impact of the world's first regulatory, multi-setting intervention on sedentary behaviour among children and adolescents (ENERGISE): a natural experiment evaluation.

BACKGROUND: Regulatory actions are increasingly used to tackle issues such as excessive alcohol or sugar intake, but such actions to reduce sedentary behaviour remain scarce. World Health Organization (WHO) guidelines on sedentary behaviour call for system-wide policies. The Chinese government introduced the world's first nation-wide multi-setting regulation on multiple types of sedentary behaviour in children and adolescents in July 2021. This regulation restricts when (and for how long) online gaming businesses can provide access to pupils; the amount of homework teachers can assign to pupils according to their year groups; and when tutoring businesses can provide lessons to pupils. We evaluated the effect of this regulation on sedentary behaviour safeguarding pupils. METHODS: With a natural experiment evaluation design, we used representative surveillance data from 9- to 18-year-old pupils before and after the introduction of the regulation, for longitudinal (n = 7,054, matched individuals, primary analysis) and repeated cross-sectional (n = 99,947, exploratory analysis) analyses. We analysed pre-post differences for self-reported sedentary behaviour outcomes (total sedentary behaviour time, screen viewing time, electronic device use time, homework time, and out-of-campus learning time) using multilevel models, and explored differences by sex, education stage, residency, and baseline weight status. RESULTS: Longitudinal analyses indicated that pupils had reduced their mean total daily sedentary behaviour time by 13.8% (95% confidence interval [CI]: -15.9 to -11.7%, approximately 46 min) and were 1.20 times as likely to meet international daily screen time recommendations (95% CI: 1.01 to 1.32) one month after the introduction of the regulation compared to the reference group (before its introduction). They were on average 2.79 times as likely to meet the regulatory requirement on homework time (95% CI: 2.47 to 3.14) than the reference group and reduced their daily total screen-viewing time by 6.4% (95% CI: -9.6 to -3.3%, approximately 10 min). The positive effects were more pronounced among high-risk groups (secondary school and urban pupils who generally spend more time in sedentary behaviour) than in low-risk groups (primary school and rural pupils who generally spend less time in sedentary behaviour). The exploratory analyses showed comparable findings. CONCLUSIONS: This regulatory intervention has been effective in reducing total and specific types of sedentary behaviour among Chinese children and adolescents, with the potential to reduce health inequalities. International researchers and policy makers may explore the feasibility and acceptability of implementing regulatory interventions on sedentary behaviour elsewhere.

Synergistic suppression of BDNF via epigenetic mechanism deteriorating learning and memory impairment caused by Mn and Pb co-exposure.

Microglia, the resident immune cells of the central nervous system (CNS), play a dual role in neurotoxicity by releasing the NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome and brain-derived neurotrophic factor (BDNF) in response to environmental stress. Suppression of BDNF is implicated in learning and memory impairment induced by exposure to manganese (Mn) or lead (Pb) individually. Methyl CpG Binding Protein 2 (MeCp2) and its phosphorylation status are related to BDNF suppression. Protein phosphatase2A (PP2A), a member of the serine/threonine phosphatases family, dephosphorylates substrates based on the methylation state of its catalytic C subunit (PP2Ac). However, the specific impairment patterns and molecular mechanisms resulting from co-exposure to Mn and Pb remain unclear. Therefore, the purpose of this study was to explore the effects of Mn and Pb exposure, alone and in combination, on inducing neurotoxicity in the hippocampus of mice and BV2 cells, and to determine whether simultaneous exposure to both metals exacerbate their toxicity. Our findings reveal that co-exposure to Mn and Pb leads to severe learning and memory impairment in mice, which correlates with the accumulation of metals in the hippocampus and synergistic suppression of BDNF. This suppression is accompanied by up-regulation of the epigenetic repressor MeCp2 and its phosphorylation status, as well as demethylation of PP2Ac. Furthermore, inhibition of PP2Ac demethylation using ABL127, an inhibitor for its protein phosphatase methylesterase1 (PME1), or knockdown of MeCp2 via siRNA transfection in vitro effectively increases BDNF expression and mitigates BV2 cell damage induced by Mn and Pb co-exposure. We also observe abnormal activation of microglia characterized by enhanced release of the NLRP3 inflammasome, Casepase-1 and pro-inflammatory cytokines IL-1ß, in the hippocampus of mice and BV2 cells. In summary, our experiments demonstrate that simultaneous exposure to Mn and Pb results in more severe hippocampus-dependent learning and memory impairment, which is attributed to epigenetic suppression of BDNF mediated by PP2A regulation.

Air pollution associated with incidence and progression trajectory of chronic lung diseases: a population-based cohort study.

BACKGROUND: No prior study has examined the effects of air pollution on the progression from healthy to chronic lung disease, subsequent chronic lung multimorbidity and further to death. METHODS: We used data from the UK Biobank of 265 506 adults free of chronic lung disease at recruitment. Chronic lung multimorbidity was defined as the coexistence of at least two chronic lung diseases, including asthma, chronic obstructive pulmonary disease and lung cancer. The concentrations of air pollutants were estimated using land-use regression models. Multistate models were applied to assess the effect of air pollution on the progression of chronic lung multimorbidity. RESULTS: During a median follow-up of 11.9 years, 13 863 participants developed at least one chronic lung disease, 1055 developed chronic lung multimorbidity and 12 772 died. We observed differential associations of air pollution with different trajectories of chronic lung multimorbidity. Fine particulate matter showed the strongest association with all five transitions, with HRs (95% CI) per 5 µg/m3 increase of 1.31 (1.22 to 1.42) and 1.27 (1.01 to 1.57) for transitions from healthy to incident chronic lung disease and from incident chronic lung disease to chronic lung multimorbidity, and 1.32 (1.21 to 1.45), 1.24 (1.01 to 1.53) and 1.91 (1.14 to 3.20) for mortality risk from healthy, incident chronic lung disease and chronic lung multimorbidity, respectively. CONCLUSION: Our study provides the first evidence that ambient air pollution could affect the progression from free of chronic lung disease to incident chronic lung disease, chronic lung multimorbidity and death.

Cultural adaptations and methodological innovations to group model building for the systems actions to reduce malnutrition in all its forms in Southeast Asian countries and China (SYSTAM CHINA-SEACS International Consortium) project.

BACKGROUND: Group Model Building (GMB) is a participatory system dynamics method increasingly used to address complex public health issues like obesity. GMB represents a set of well-defined steps to engage key stakeholders to identify shared drivers and solutions of a given problem. However, GMB has not yet been applied specifically to develop multi-duty interventions that address multiple inter-related issues such as malnutrition in all its forms (MIAIF). Moreover, a recent systematic review of empirical applications of a systems approach to developing obesity interventions found no published work from non-western, low- and middle-income countries (LMICs). In this paper we describe adaptations and innovations to a common GMB process to co-develop systemic MIAIF interventions with Chinese decision-makers. METHODS: We developed, piloted and implemented multiple cultural adaptations and two methodological innovations to the commonly used GMB process in Fang Cheng Gang city, China. We included formal, ceremonial and policy maker engagement events before and between GMB workshops, and incorporated culturally tailored arrangements during participant recruitment (officials of the same seniority level joined the same workshop) and workshop activities (e.g., use of individual scoring activities and hand boards). We made changes to the commonly used GMB activities which enabled mapping of shared drivers of multiple health issues (in our case MIAIF) in a single causal loop diagram. We developed and used a 'hybrid' GMB format combining online and in person facilitation to reduce travel and associated climate impact. RESULTS: Our innovative GMB process led to high engagement and support from decision-makers representing diverse governmental departments across the whole food systems. We co-identified and prioritised systemic drivers and intervention themes of MIAIF. The city government established an official Local Action Group for long-term, inter-departmental implementation, monitoring and evaluation of the co-developed interventions. The 'hybrid' GMB format enabled great interactions while reducing international travel and mitigating limitations of fully online GMB process. CONCLUSIONS: Cultural and methodological adaptations to the common GMB process for an Asian LMIC setting were successful. The 'hybrid' GMB format is feasible, cost-effective, and more environmentally friendly. These cultural adaptations could be considered for other Asian settings and beyond to address inter-related, complex issues such as MIAIF.

Associations of blood lead, cadmium, and mercury with resistant hypertension among adults in NHANES, 1999-2018.

BACKGROUND: Resistant hypertension (RHTN), a clinically complex condition with profound health implications, necessitates considerable time and allocation of medical resources for effective management. Unraveling the environmental risk factors associated with RHTN may shed light on future interventional targets aimed at reducing its incidence. Exposure to heavy metal has been linked to an increased risk of hypertension, while the relationship with RHTN remains poorly understood. METHODS: Using the 1999-2018 National Health and Nutrition Examination Survey (NHANES) data, we examined the association of blood lead (Pb), cadmium (Cd), and mercury (Hg) with RHTN using a multinomial logistic regression model. The combined effects of the metals and the contribution of each metal were assessed using a weighted quantile sum (WQS) analysis. RESULTS: A total of 38281 participants were included in the analysis. Compared with no resistant hypertension (NRHTN), per 1 µg/dL increase in blood Pb concentration, the proportion of RHTN increased by 16% [adjusted odds ratio (aOR), 1.16; 95% confidence interval (CI) 1.01-1.32]. When analyzed by quartiles (Q), the aOR [95% CI] for Pd was 1.30[1.01,1.67] (Q4 vs. Q1); there was a significant dose-response relationship (p < 0.05). Likewise, as a continuous variable, each 1 µg/dL increase in blood Cd level was associated with a 13% increase in the proportion of RHTN (aOR: 1.13; 95%CI: [1.00,1.27]); when analyzed as quartile, aOR [95% CI] for Cd were 1.30[1.01,1.69] (Q3 vs. Q1), and 1.35[1.03,1.75] (Q4 vs. Q1); the dose-response relationship was significant (p < 0.05). WQS analysis showed a significant combined effects of Pb, Cd, and Hg on RHTN, with Pb as the highest weight (0.64), followed by Cd (0.25) and Hg (0.11). Stratified analysis indicated that the associations for the two heavy metals were significant for participants who were male, ≼ 60 years old, and with kidney dysfunction. CONCLUSION: Findings of this study with national data provide new evidence regarding the role of environmental heavy metal exposure in RHTN. The prevention strategies aimed at reducing heavy metal exposure should particularly focus on Americans who are middle-aged, male, and afflicted with kidney dysfunction.

Circular RNA circGLIS3 promotes bladder cancer proliferation via the miR-1273f/SKP1/Cyclin D1 axis.

Extensive research confirmed that circRNA can play a regulatory role in various stages of tumors by interacting with various molecules. Identifying the differentially expressed circRNA in bladder cancer and exploring its regulatory mechanism on bladder cancer progression are urgent. In this study, we screened out a circRNA-circGLIS3 with a significant upregulation trend in both bladder cancer tissues and cells. Bioinformatics prediction results showed that circGLIS3 may be involved in multiple tumor-related pathways. Function gain and loss experiments verified circGLIS3 can affect the proliferation, migration, and invasion of bladder cancer cells in vitro. Moreover, silencing circGLIS3 inhibited bladder cancer cell growth in vivo. Subsequent research results indicated circGLIS3 regulated the expression of cyclin D1, a cell cycle-related protein, and cell cycle progression. Mechanically, circGLIS3 upregulates the expression of SKP1 by adsorbing miR-1273f and then promotes cyclin D1 expression, ultimately promoting the proliferation of bladder cancer cells. In summary, our study indicates that circGLIS3 plays an oncogene role in the development of bladder cancer and has potential to be a candidate for bladder cancer.

High-Temperature Soup Foods in Plastic Packaging Are Associated with Phthalate Body Burden and Expression of Inflammatory mRNAs: A Dietary Intervention Study.

Plastic packaging material is widely used to package high-temperature soup food in China, but this combination might lead to increased exposure to phthalates. The health effects and potential biological mechanisms have not been well studied. This study aimed to examine urinary phthalate metabolites and the expression of inflammatory cytokines in the blood before, during, and after a "plastic-packaged high-temperature soup food" dietary intervention in healthy adults. The results showed that compared with those in the preintervention period, urinary creatinine-adjusted levels of monomethyl phthalate (MMP), mono-n-butyl phthalate (MBP), mono-isobutyl phthalate (MIBP), and total phthalate metabolites in the intervention period were significantly higher, with increases of 71.6, 41.8, 38.8, and 29.8% for MMP, MBP, MIBP, and the total phthalate metabolites, respectively. After intervention, the mean levels of IL-1ß, IL-4, and TNF-α mRNA increased by 19.0, 21.5, and 25.0%, respectively, while IL-6 and IFN-γ mRNA decreased by 24.2 and 32.9%, respectively, when compared with the preintervention period. We also observed that several phthalates were associated with the mRNA or protein expression of IL-8, TNF-α, and IL-10. Therefore, consumption of plastic-packaged high-temperature soup food was linked to increased phthalate exposure and might result in significant changes in mRNA expression of several inflammatory cytokines.

Investigation of Temperature Variations and Extreme Temperature Differences for the Corrugated Web Steel Beams under Solar Radiation.

Due to the coupling impacts of solar radiation, wind, air temperature and other environmental parameters, the temperature field of steel structures is significantly non-uniform during their construction and service stages. Corrugated web steel beams have gained popularity in structural engineering during the last few decades, while their thermal actions are barely investigated. In this paper, both experimental and numerical investigations were conducted to reveal the non-uniform features and time variation of the corrugated web steel beams under various environmental conditions. The heat-transfer simulation model was established and verified using the experimental temperature data. Both the experiment and simulation results demonstrate that the steel beam has a complicated and non-uniform temperature field. Moreover, 2-year continuous numerical simulations of steel beams' thermal actions regarding eight different cities were carried out to investigate the long-term temperature variations. Finally, based on the long-term simulation results and extreme value analysis (EVA), the representative values of steel beams' daily temperature difference with a 50-year return period were determined. The extreme temperature difference of the steel beam in Harbin reached up to 46.9 °C, while the extreme temperature difference in Haikou was 28.8 °C. The extreme temperature difference is highly associated with the steel beam's location and surrounding climate. Ideally, the outcomes will provide some contributions for the structural design regarding the corrugated web steel beam.

Structural Damage Identification Based on Transmissibility in Time Domain.

Structural damage identification technology is of great significance to improve the reliability and safety of civil structures and has attracted much attention in the study of structural health monitoring. In this paper, a novel structural damage identification method based on transmissibility in the time domain is proposed. The method takes the discrepancy of transmissibility of structure response in the time domain before and after damage as the basis of finite element model updating. The damage is located and quantified through iteration by minimizing the difference between the measurements at gauge locations and the reconstruction response extrapolated by the finite element model. Taking advantage of the response reconstruction method based on empirical mode decomposition, damage information can be obtained in the absence of prior knowledge on excitation. Moreover, this method directly collects time-domain data for identification without modal identification and frequent time-frequency conversion, which can greatly improve efficiency on the premise of ensuring accuracy. A numerical example is used to demonstrate the overall damage identification method, and the study of measurement noise shows that the method has strong robustness. Finally, the present work investigates the method through a simply supported overhanging beam. The experiments collect the vibration strain signals of the beam via resistance strain gauges. The comparison between identification results and theoretical values shows the effectiveness and accuracy of the method.

Dysregulated APP expression and α-secretase processing of APP is involved in manganese-induced cognitive impairment.

Excessive exposure to manganese (Mn) can cause cognitive impairment, a common feature of Alzheimer's disease (AD), but the mechanisms remain unclear. Amyloid precursor protein (APP) is key to AD pathogenesis, and whether APP and its secretase processing are involved in Mn-induced cognitive impairment remains unknown. In the present study, we established a model of Mn-induced neurotoxicity in vivo (male C57BL/6, 0-100 mg/kg Mn, 90 days, gastric gavage) and in vitro (Neuro-2a (N2a) cells, 0-800 µM Mn for 24 h; APP overexpression and APP shRNA N2a cells, 0 and 800 µM Mn for 24 h). We found impaired cognition of Mn-treated mice. Both in vivo and in vitro results consistently showed that Mn exposure inhibited the expression of APP, α-secretase, soluble APP alpha protein (sAPPα), and synapse proteins as well as the activity of α-secretase. However, Mn exposure showed no effect on the protein levels of ß-secretase, Aß40, and Aß42 or the activity of ß-secretase. Collectively, these findings demonstrate key roles of APP and its α-secretase processing in the regulation of Mn-induced cognitive impairment, which may act as a target for ameliorating Mn-induced neurotoxicity.

Combined exposure to multiple metals and cognitive function in older adults.

Single toxic metal exposure has been reported to be associated with impaired cognitive function, but less is known about the effects of combined exposure to multiple metals. The aim of the study was to investigate the potential associations and interactions of multiple metals with cognitive function in older adults using multi-pollutants approach. A cross-sectional study was conducted in a total of 2879 participants aged ≥ 60 years old. We systematically measured levels of 22 blood metals and used the Mini-Mental State Examination (MMSE) to assess the cognitive function. The least absolute shrinkage and selection operator (LASSO) penalized regression was applied to identify independently main metals. Adjusted estimates of cognitive function with selected metals were investigated by generalized linear regression in the multi-metal model. We found that calcium, titanium, vanadium, copper, zinc, arsenic, selenium, rubidium, molybdenum, cadmium, barium, and lead were independently identified based on LASSO penalized regression. The multi-metal model showed a higher MMSE of 0.384 (95% CI: 0.122-0.646) for a 1-SD increment in log-transformed rubidium and a lower MMSE of 0.460 (95% CI: - 0.706 to - 0.214) for a 1-SD increment in log-transformed cadmium (P < 0.05). The significantly negative associations between cadmium and cognitive function were attenuated to null accompanying with increasing concentrations of rubidium (P interaction = 0.256). Our findings suggested that blood rubidium and cadmium were mainly associated with cognitive function when accounting for co-exposure to other metals and higher level of rubidium appeared to attenuate the toxic effects of cadmium on cognitive function in older adults.

Experimental Study of Aerodynamic Interference Effects for a Suspended Monorail Vehicle-Bridge System Using a Wireless Acquisition System.

The suspended monorail (SM) vehicle-bridge system has been considered a promising modern transit mode due to its clear advantages: low pollution, high safety, convenient construction, and low cost. The wind-induced response can significantly affect the running safety and comfort of this type of vehicle due to its special suspended position from a fixed track. This study is the first to systematically investigate its aerodynamic characteristics and interference effects under various spacing ratios using wind tunnel tests and numerical simulations. A high level of agreement between the wind tunnel test and CFD (computational fluid dynamics) results was obtained, and the aerodynamic interference mechanism can be well explained using the CFD technique from a flow field perspective. A wireless wind pressure acquisition system is proposed to achieve synchronization acquisition for multi wind pressure test taps. The paper confirms that (1) the proposed wireless wind pressure acquisition system performed well; (2) the aerodynamic coefficients of the upstream vehicle and bridge were nearly unchanged for vehicle-bridge combinations with varying spacing ratios; (3) the aerodynamic interference effects were amplified when two vehicles meet, but the effects decrease as the spacing ratio increases; (4) the aerodynamic force coefficients, mean, and root mean square (RMS) wind pressure coefficients for the downstream vehicle and bridge are readily affected by the upstream vehicle; (5) the vortex shedding frequencies of vehicles and bridges can be readily obtained from the lift force spectra, and they decrease as the spacing ratio increases; and (6) a spacing ratio of 3.5 is suggested in the field applications to ensure the running safety and stability of the SM vehicle-bridge system under exposure to crosswinds.

Comparations of major and trace elements in soil, water and residents' hair between longevity and non-longevity areas in Bama, China.

Natural environment is an important factor affecting longevity. Soil, water and hair samples from Bama were assayed to investigate the effects of elements on the regional longevity. The concentrations of Cd, Co and Mg in soil and Co in drinking water were significantly higher in longevity area than those in non-longevity area (p < 0.05). The concentrations of K, Mo, Na, Pb and V in soil, Mg, Na, Fe, Li and Mn in drinking water and I, K, Mg, Mn, Na and Sr in hair were significantly lower in longevity area than those in non-longevity area (p < 0.05). Mg, Mn, Na and Sr in hair were affected by soil and drinking water. Our results indicate that adequate concentration of Mg in soil might benefit longevity, excessive concentrations of Na in soil, Mg, Mn and Na in drinking water and Mg, Mn, Na and Sr in hair might reduce lifespan of local residents.

High manganese exposure decreased the risk of high triglycerides in workers: a cross-sectional study.

BACKGROUND: Manganese (Mn) participates in lipid metabolism. However, the associations between Mn exposure and dyslipidaemia is unclear. METHODS: This was a cross-sectional study. Data were collected from the 2017 the Mn-exposed workers healthy cohort (MEWHC). Finally, 803 occupationally Mn-exposed workers included in the study. The workers were divided into two groups. The grouping of this study was based on Mn-Time Weighted Averages (Mn-TWA). The high-exposure group included participants with Mn-TWA greater than 0.15 mg/m3. The low-exposure group included participants with Mn-TWA less than or equal to 0.15 mg/m3. Mn-TWA levels and dyslipidaemia were assessed. RESULTS: After adjustment for seniority, sex, cigarette consumption, alcohol consumption, high-fat diet frequency, medicine intake in the past two weeks, egg intake frequency, drinking tea, WHR, and hypertension, Mn-TWA levels was negatively correlated with high triglycerides (TG) risk in workers overall (OR = 0.51; 95% CI: 0.36, 0.73; p <  0.01). The results of males and females were consistent (OR = 0.53; 95% CI: 0.34, 0.81; p <  0.01) and (OR = 0.47; 95% CI: 0.24, 0.94; p <  0.01), respectively. By performing interactions analyses of workers overall, we observed no significant interactions among confounders. Mn-TWA levels and pack-years on high TG risk (relative excess risk for the interactions (RERI = 2.29, 95% CI: - 2.07, 6.66), (RERI) = 2.98, 95% CI: - 2.30, 8.26). Similarly, smoking status, drinking status, high-fat diet frequency, and Waist-to-Hip Ratio (WHR) showed non-significant interactions with Mn-TWA levels on high TG risk. CONCLUSIONS: This research indicates that high Mn exposure was negatively related to high TG risk in workers.

Occupational exposure to manganese and risk of creatine kinase and creatine kinase-MB elevation among ferromanganese refinery workers.

BACKGROUND: Elevated exposure to manganese (Mn) could induce cardiovascular dysfunction. However, limited research is available on the effects of occupational Mn exposure on myocardial enzymes. We aimed to evaluate the relationships between Mn exposure and myocardial enzyme elevation among Mn-exposed workers. METHODS: Data were from a follow-up investigation of a Mn-exposed workers healthy cohort in 2017. A total of 744 workers were divided into low-exposure and high-exposure groups according to Mn time-weighted average (Mn-TWA) of less than or equal to 0.15 mg/m3 or greater than 0.15 mg/m3 , respectively. Serum levels of myocardial enzymes, including creatine kinase (CK) and creatine kinase-MB (CK-MB), lactic dehydrogenase, α-hydroxybutyrate dehydrogenase, and aspartate transaminase, were assessed, as well as airborne Mn exposure levels. RESULTS: After adjustment for sex, body mass index, seniority, education, current smoking status, current drinking status, and hypertension, Mn-TWA levels were positively associated with the risk of CK elevation (odds ratio [OR] = 1.47 (95% confidence interval [CI]: 1.18-1.83) per interquartile range [IQR] increase), and risk of CK-MB elevation [OR = 1.57 (95% CI: 1.03-2.38) per IQR increase]. In a stratified analysis, Mn-TWA levels were positively correlated with CK elevation in workers of seniority greater than 19 years, male workers, current smokers, and drinkers. CONCLUSION: Our results suggest that occupational exposure to Mn is associated with increased risk of CK and CK-MB elevation. The potential mechanisms of the associations between airborne exposure to Mn and increased risk of these myocardial enzyme elevations warrant further investigation.

PM2.5-inducible long non-coding RNA (NONHSAT247851.1) is a positive regulator of inflammation through its interaction with raf-1 in HUVECs.

Several studies have demonstrated that PM2.5 inhalation is associated with an increased risk of cerebrovascular disease (CVD), in which inflammation plays an important role. The mechanisms of this disease are not fully understood to date. Long non-coding RNAs (lncRNAs) are involved in many pathophysiological processes, such as immune responses; however, their functions associated with inflammation are largely unexplored. High-throughput sequencing assay and obtained numerous lncRNAs that altered the expression in response to PM2.5 treatment in HUVECs. NONHSAT247851.1 was also identified, which was significantly up-regulated to control the expression of immune response genes. Mechanistically, the results indicated that NONHSAT247851.1 knockdown reduced the expression of IL1ß. In study, we investigated NONHSAT247851.1 as a promoter in regulating immune response genes via binding with raf-1 to regulate the phosphorylation level of p65 protein in HUVECs. The data collected suggests that NONHSAT247851.1 regulates inflammation via interaction with raf-1 to control the inflammatory expression in PM2.5 exposure.

Dynamic Responses of a Metro Train-Bridge System under Train-Braking: Field Measurements and Data Analysis.

This paper focuses on the dynamic responses of a metro train-bridge system under train-braking. Experiments were performed on the elevated Metro Line 21 of Guangzhou (China). A continuous, three-span, rigid-frame bridge (42 m + 65 m + 42 m) and a standard B-type metro train were selected. The acceleration signals were measured at the center-points of the main span and one side-span, and the acceleration signals of the car body and the bogie frame were measured simultaneously. The train-bridge system's vibration characteristics and any correlations with time and frequency were investigated. The Choi-Williams distribution method and wavelet coherence were introduced to analyze the obtained acceleration signals of the metro train-bridge system. The results showed that the Choi-Williams distribution provided a more explicit understanding of the time-frequency domain. The correlations between different parts of the bridge and the train-bridge system under braking conditions were revealed. The present study provides a series of measured dynamic responses of the metro train-bridge system under train-braking, which could be used as a reference in further investigations.

Association of liver and kidney functions with Klotho gene methylation in a population environment exposed to cadmium in China.

Exposure to the heavy metal cadmium has adverse effects on human health, including DNA methylation. This study aimed to investigate the effects of cadmium on liver and kidney functions and Klotho gene methylation and to explore the relationship of methylation level with indicators of liver and kidney functions. Graphite furnace atomic absorption spectrometry was conducted to determine urinary cadmium, and an automatic biochemical analyzer was used to detect indices of liver and kidney functions. PCR pyrosequencing was performed to detect the methylation rate of Klotho. One-way ANOVA was adopted to compare the differences between groups, and the linear correlation to variables was analyzed. Cadmium exposure was negatively correlated with albumin level (r=-0.143, p=0.021) and positively correlated with urinary ß2-microglobulin level (r=0.229, p<0.001). However, the methylation levels of Klotho gene was decreased and increased by low and high doses of cadmium exposure, respectively. And Klothomethylation levels were negatively correlated with albumin levels and positively correlated with ß2-microglobulin levels.In this study, cadmium exposure affects liver and kidney functions as well as Klotho methylation levels, but the effect on Klotho methylation levels is not linear. Klotho methylation levels also influence liver and kidney functions.

Pivotal role of cAMP-PKA-CREB signaling pathway in manganese-induced neurotoxicity in PC12 cells.

Manganese (Mn) plays a critical role in individual growth and development, yet excessive exposure can result in neurotoxicity, especially cognitive impairment. Neuronal apoptosis is considered as one of the mechanisms of Mn-induced neurotoxicity. Recent evidence suggests that cAMP-PKA-CREB signaling regulates apoptosis and is associated with cognitive function. However, whether this pathway participates in Mn-induced neurotoxicity is not completely understood. To fill this gap, in vitro cultures of PC12 cells were exposed to 0, 400, 500, and 600 µmol/L Mn for 24 hours, respectively. Another group of cells were pretreated with 10.0 µmol/L rolipram (a phosphodiesterase-4 [PDE4] inhibitor) for 1 hour followed by 500 µmol/L Mn exposure for 24 hours. Flow cytometry, immunofluorescence staining, enzyme-linked immunosorbent assay, and Western blot analysis were used to detect the apoptosis rate, protein levels of PDE4, cAMP signaling, and apoptosis-associated proteins, respectively. We found that Mn exposure significantly inhibited cAMP signaling and protein expression of Bcl-2, while increasing apoptosis rate, protein levels of PDE4, Bax, activated caspase-3, and activated caspase-8 in PC12 cells. Pretreatment of rolipram ameliorated Mn-induced deficits in cAMP signaling and apoptosis. These findings demonstrate that cAMP-PKA-CREB signaling pathway-induced apoptosis is involved in Mn-induced neurotoxicity.