Genome-Wide Association and Functional Studies Identify SCML4 and THSD7A as Novel Susceptibility Genes for Coronary Artery Disease.

OBJECTIVE: The genetic contribution to coronary artery disease (CAD) remains largely unclear. We combined genetic screening with functional characterizations to identify novel loci and candidate genes for CAD. APPROACH AND RESULTS: We performed genome-wide screening followed by multicenter validation in 8 cohorts consisting of 21 828 participants of Han ethnicity and identified 3 novel intragenic SNPs (single nucleotide polymorphisms), rs9486729 (SCML4 [Scm polycomb group protein-like 4]; odds ratio, 1.25; 95% CI, 1.17-1.34; P=3.51×10-11), rs17165136 (THSD7A [thrombospondin type 1 domain-containing 7A]; odds ratio 1.28; 95% CI, 1.21-1.35; P<1.00×10-25), and rs852787 (DAB1 [disabled-1]; odds ratio, 1.29; 95% CI, 1.21-1.38; P=2.02×10-14), associated with CAD with genome-wide significance. The risk allele of rs9486729 and protective allele of rs17165136 were associated with the decreased expression of their host genes, SCML4 and THSD7A, respectively, whereas rs852787 did not have transcriptional effects on any gene. Knockdown of SCML4 activated endothelial cells by increasing the expression of IL-6, E-selectin, and ICAM and weakened their antiapoptotic activity, whereas the knockdown of THSD7A had little effect on these endothelial cell functions but attenuated monocyte adhesion via decreasing the expression of ICAM, L-selectin, and ITGB2. We further showed that inhibiting the expression of SCML4 exacerbated endothelial dysfunction and vascular remodeling in a rat model with partial carotid ligation. CONCLUSIONS: We identify 3 novel loci associated with CAD and show that 2 genes, SCML4 and THSD7A, make functional contributions to atherosclerosis. How rs852787 and its host gene DAB1 are linked to CAD needs further studies.

Inhalation exposure and potential health risk estimation of lanthanides elements in PM2.5 associated with rare earth mining areas: a case of Baotou city, northern China.

Particulate pollution, especially PM2.5 (particles with an aerodynamic equivalent diameter of 2.5 µm or less), has received increased attention in China recently. In this study, PM2.5 samples were collected in August 2013 and April 2014 from different regions of Baotou, the largest rare earth elements (REEs) processing city in northern China. The concentrations and distribution patterns of REEs in PM2.5 were analyzed, and the inhalation exposure to REEs associated with PM2.5 was assessed. The results showed that the REEs levels were 56.9 and 15.3 ng m-3 in August 2013 and April 2014, respectively. These values are much higher than those in non-REEs mining areas. The distribution patterns of REEs exhibited LREE enrichment. The Eu and Ce anomalies displayed slightly positive and negative values, respectively, which were in accordance with the background soil and ore. The average daily intake amounts of REEs for population through inhalation exposure of PM2.5 in Baotou were in the range of 5.09 × 10-7 to 2.25 × 10-5 mg kg-1 day-1.

Diesel exhaust exposure induced squamous metaplasia of corneal epithelium via yes-associated protein activation.

Atmospheric pollution has been demonstrated to be associated with ocular surface diseases characterized by corneal epithelial damage, including impaired barrier function and squamous metaplasia. However, the specific mechanisms underlying the impact of atmospheric pollution on corneal damage are still unknow. To address this gap in knowledge, we conducted a study using a whole-body exposure system to investigate the detrimental effects of traffic-related air pollution, specifically diesel exhaust (DE), on corneal epithelium in C57BL/6 mice over a 28-day period. Following DE exposure, the pathological alterations in corneal epithelium, including significant increase in corneal thickness and epithelial stratification, were observed in mice. Additionally, exposure to DE was also shown to disrupt the barrier functions of corneal epithelium, leading to excessive proliferation of basal cells and even causing squamous metaplasia in corneal epithelium. Further studies have found that the activation of yes-associated protein (YAP), characterized by nuclear translocation, may play a significant role in DE-induced corneal squamous metaplasia. In vitro assays confirmed that DE exposure triggered the YAP/ß-catenin pathway, resulting in squamous metaplasia and destruction of barrier functions. These findings provide the preliminary evidence that YAP activation is one of the mechanisms of the damage to corneal epithelium caused by traffic-related air pollution. These findings contribute to the knowledge base for promoting eye health in the context of atmospheric pollution.

Catchment land use effect on mercury concentrations in lake sediments: A high-resolution study of Qinghai Lake.

Mercury (Hg) contamination in aquatic environments presents a significant ecological and human health concern. This study explored the relationship between catchment land use and Hg concentrations within Qinghai Lake sediment, the largest lake in China, situated on the Qinghai-Tibet plateau. The study entailed detailed mapping of Hg sediment concentrations and a subsequent environmental risk assessment. Considering the complex nature of the plateau landform and surface vegetation, the study area was delineated at a 100 km radius centered on Qinghai Lake, which was divided into 30 sectors to quantify relationships between land use and the sediment Hg concentration. The results revealed a mean sediment Hg concentration of 29.91 µg/kg, which was elevated above the background level. Kendall's correlation analysis revealed significant but weak associations between sediment Hg concentrations and three land use types: grassland (rangeland and trees) (rs = 0.27, p < 0.05), crops (rs = -0.37, p < 0.05), and bare ground (rs = -0.25, p < 0.1), suggesting that growing areas of grassland correlated with higher Hg levels in the lake sediment, in contrast to bare ground or crops area, which correlated with lower Hg concentrations. Multiple linear regression models also observed weak negative relationships between bare ground and crops with sediment Hg concentration. This research methodology enhances our understanding of the impact of land use on Hg accumulation in lake sediments and underscores the need for integrated watershed management strategies to mitigate Hg pollution in Qinghai Lake.

Cosorption of Zn(II) and chlortetracycline onto montmorillonite: pH effects and molecular investigations.

Ionic antibiotics and metals generally coexist, and their interaction can affect their sorption behaviors onto soil minerals, therefore determining their environmental hazards. This study investigated the sorption and cosorption of Zn(II) and chlortetracycline (CTC) onto montmorillonite at different solution pH (3-10) using batch experiments and extended X-ray absorption fine structure (EXAFS) analysis. The Langmuir model could reproduce well the sorption isotherms of Zn(II) and CTC. The presence of CTC/Zn(II) could promote the maximum sorption capacity (Qm) of Zn(II)/CTC, based on site energy distribution (SED) theory. Generally, Zn(II) sorption increased with pH increasing. Comparatively, CTC sorption decreased as pH increased till approximately pH 5.0, then increased continuously with pH increasing. Both CTC and Zn(II) co-existence enhanced their individual sorption in both acidic and neutral environments. The processes behind CTC and Zn(II) sorption mainly included cation exchange and surface complexation. The EXAFS data evidenced that the presence of CTC could alter the species of Zn(II) on montmorillonite via surface complexation at pH 4.5 and 7.5, with Zn-CTC complexes being the predominant species on montmorillonite at pH 7.5. At pH 9.5, Zn(II) may exist onto montmorillonite in precipitated form similar to Zn-Al hydrotalcite-like compound (HTlc) regardless of CTC presence.

Identification of areas vulnerable to soil erosion and risk assessment of phosphorus transport in a typical watershed in the Loess Plateau.

Soil erosion is an increasingly serious eco-environmental problem and an important driver of phosphorus loss, which not only reduces soil productivity but also decreases water availability. The integration of the universal soil loss equation (USLE) and the geographic information system (GIS) technique is globally popular for erosion prediction and assessment. The Fen River basin is located in the east of the Loess Plateau and has eco-environmental problems of soil erosion and eutrophication because of excess phosphorus content. This study attempted to use the USLE model to evaluate soil erosion and the transport of the resulting particulate phosphorus in the Fen River basin under a GIS framework. The results showed that soil erosion in 15.8% of the study area exceeded 8000 t/(km2·a) and was mainly distributed in the upper Fen River basin. Soil erosion was greatest in the bareland area, with an average of approximately 1.22 × 104 t/(km2·a), followed by that in grassland. Soil erosion in the study area is most sensitive to the rainfall erodibility (R), followed by the soil erodibility (K), topographic factors including slope steepness (S) and slope length (L), the soil and water conservation factor (P), and the vegetation cover and management factor (C). Similar to soil erosion, the high-risk areas of particulate phosphorus transport were mainly concentrated in the upper reaches of the basin. The study also pointed out that the combined use of available data sources with the USLE model and GIS technique is a viable option to calculate soil erosion and assess the risk of particulate phosphorus transport, which could provide a scientific basis for reducing soil erosion and controlling phosphorus migration.

Assessment of reactive oxygen species production and genotoxicity of rare earth mining dust: Implications for public health and mining management.

Mining rare earth elements (REEs) can release large amounts of metal(loid)-rich dust, which can pose significant health risks to local residents. However, compared to other types of particulates, toxicity of mining dust has been largely overlooked. To provide experimental evidence on toxicity of REE mine dust, the study assessed the oxidative stress potential and genotoxicity of inhalable particles collected in a REE mining area, and associated toxicological response with source compositions. Both source types (i.e., mine and tailing area) and distances from source (i.e., industrial and residential areas) were considered when selecting the 44 sampling sites. The particle samples contained 2.3-3.5 folds higher concentrations of tested metal(loid)s than background concentrations in soil. Specially, elevated Fe, REEs, Cd, Pb were found. In spite of low cytotoxicity in lung epithelial A549 cells, there was increased cellular ROS production by of particle exposure. Samples with higher mining-originated source contributions (Provenance Index <0.3) had higher cellular ROS production (1.72 fold, 95%CI: 1.66-1.79 fold) than samples with lower mining contributions (1.58 fold, 95%CI: 1.52-1.65 fold). The factors soil (~46%), mine (~22%), and heavy metal (~20%) sources were recognized by source apportionment analysis as the main contributors to cellular ROS production; importantly, mine and heavy metal sources counted more in industrial samples. While samples generated genotoxicity, there were no differences in DNA damage between the location groups of sampling. Collectively, the results indicate that particles in mining areas may cause ROS production and DNA damage in lung cells depending on mine dust. Coupled with the long-range transportation potential of mine dust, safety measures on open pit and dust disposal sites should be adopted.

Fine road dust contamination in a mining area presents a likely air pollution hotspot and threat to human health.

The road dust found in mining areas is composed of dust from multiple sources, including wind transported mineral dust from mines and tailings as well as uncovered trucks leakage. Collectively, these are then distributed via wind and traffic activity, becoming an important source of particulate matter (PM) and subsequently inhaled by pedestrians. A common practice in previous road dust risk assessments has regarded them as soil, which likely led to a significant underestimation of the actual inhaled amount. To more accurately understand the inhalation risk presented by road dust in mining areas, the study applied a detailed pollution analysis and dust dispersion model to assess the inhaled amount of road dust. Road dust samples located at different distances to the mine and tailings were collected and sieved to 10 µm (RD10). Enrichment factors (EFs) of Ce, As, Cd, and Mo exceeded 20 across most sampled sites, suggesting extreme pollution. Source analysis indicated that most of the collected RD10 had greater than half of its mass originating from the mine. To assess the risk presented by inhalation exposure to local populations, we built a method using Gaussian diffusion model and two exposure scenarios for both adults and children were considered. The level of simulated particle concentrations was comparable to that described in the literature; the inhalation of potential toxic elements (PTEs) in RD10 led to health risks for both adults and children (adult and child HI > 1, with adults CR in industrial areas >10-4). Results also indicated that a ten-fold reduction of silt load resulted in a >4-fold decrease in risk. Collectively, the results suggest that fine road dust is a potential hotspot for mineral exposure in populations living around a mine and its tailings; moreover, that effective prevention measures like road cleaning and truck regulation are urgently needed.

Source and path identification of metals pollution in a mining area by PMF and rare earth element patterns in road dust.

To better assess pollution and offer efficient protection for local residents, it is necessary to both conduct an exhaustive investigation into pollution levels and quantify its contributing sources and paths. As it is the biggest light rare earth element (REE) reserve in the world, Bayan Obo deposit releases large amounts of heavy metals into the surrounding environment. In this study, road dust from zones located at different distances to the mining area was collected and sieved using seven sizes. This allowed for subsequent analysis of size-dependent influences of mining activities. A receptor model was used to quantitatively assess mine contributions. REE distribution patterns and other REE parameters were compared with those in airborne particulates and the surrounding soil to analyze pollution paths. Results showed that 27 metals were rated as moderately to extremely polluted (2

Heavy metal bioaccessibility and health risks in the contaminated soil of an abandoned, small-scale lead and zinc mine.

The lack of management in small-scale mining operations has the potential for negative repercussions, e.g., mine collapses, compared with well-regulated large-scale mines. Here, we used an in vitro model to investigate heavy metal soil pollution characteristics and their attendant health risks in an abandoned, small-scale lead (Pb) and zinc (Zn) mine located in southwestern China that had suffered from collapse. Our results showed the following: (1) Even the mine had been closed for many years, the soil was still heavily polluted by Pb, cadmium (Cd), and Zn, and there is a risk of secondary pollution. Pb, Zn, and Cd concentrations in the mining areas were all approximately 22-42 times higher than the background soil levels of Guangxi Province. (2) Cd had the largest bioaccessibility, and mining areas tend to have soils containing more bioaccessible metals (78 ± 14%, 27 ± 4%, and 38 ± 12% for Cd, Pb, and Zn in gastric phase and 40 ± 12%, 10 ± 5%, and 19 ± 8% in intestinal phase correspondingly). (3) Results of a stepwise, multiple regression analysis revealed that the total soil content of the three metals (Pb, Zn, and Cd), TOC (total organic carbon), soil composition, and Mn content were the main impact factors for the Pb, Cd, and Zn soil bioaccessibility in study area (R2 = 0.37~0.93). (4) A health risk assessment based on Pb, Cd, and Zn bioaccessibility indicated that the health risk for people in mine area is not high (HI is 1.07 at most and CR 2.40E-6 at most for children).

High-resolution imaging of labile phosphorus and its relationship with iron redox state in lake sediments.

A thorough understanding of the labile status and dynamics of phosphorus (P) and iron (Fe) across the sediment-water interface (SWI) is essential for managing internal P release in eutrophic lakes. Fe-coupled inactivation of P in sediments is an important factor which affects internal P release in freshwater lakes. In this study, two in-situ high-resolution diffusive gradients in thin films (DGT) techniques, Zr-Oxide DGT and ZrO-Chelex DGT, were used to investigate the release characteristics of P from sediments in a large freshwater lake (Dongting Lake, China; area of 2691 km2) experiencing a regional summer algal bloom. Two-dimensional distributions of labile P in sediments were imaged with the Zr-Oxide DGT without destruction of the original structure of the sediment layer at four sites of the lake. The concentration of DGT-labile P in the sediments, ranging from 0.007 to 0.206 mg L-1, was highly heterogeneous across the profiles. The values of apparent diffusion flux (Fd) and release flux (Fr) of P varied between -0.027-0.197 mg m-2 d-1 and 0.037-0.332 mg m-2 d-1, respectively. Labile P showed a high and positive correlation (p < 0.01) with labile Fe(II) in the profiles, providing high-resolution evidence for the key role of Fe-redox cycling in labile P variation in sediments.