New Insights into MeHg Accumulation in Rice (Oryza sativa L.): Evidence from Cysteine.

The intake of methylmercury (MeHg)-contaminated rice poses immense health risks to rice consumers. However, the mechanisms of MeHg accumulation in rice plants are not entirely understood. The knowledge that the MeHg-Cysteine complex was dominant in polished rice proposed a hypothesis of co-transportation of MeHg and cysteine inside rice plants. This study was therefore designed to explore the MeHg accumulation processes in rice plants by investigating biogeochemical associations between MeHg and amino acids. Rice plants and underlying soils were collected from different Hg-contaminated sites in the Wanshan Hg mining area. The concentrations of both MeHg and cysteine in polished rice were higher than those in other rice tissues. A significant positive correlation between MeHg and cysteine in rice plants was found, especially in polished rice, indicating a close geochemical association between cysteine and MeHg. The translocation factor (TF) of cysteine showed behavior similar to that of the TF of MeHg, demonstrating that these two chemical species might share a similar transportation mechanism in rice plants. The accumulation of MeHg in rice plants may vary due to differences in the molar ratios of MeHg to cysteine and the presence of specific amino acid transporters. Our results suggest that cysteine plays a vital role in MeHg accumulation and transportation inside rice plants.

Using Mercury Stable Isotopes to Quantify Directional Soil-Atmosphere Hg(0) Exchanges in Rice Paddy Ecosystems: Implications for Hg(0) Emissions to the Atmosphere from Land Surfaces.

Gaseous elemental mercury [Hg(0)] emissions from soils constitute a large fraction of global total Hg(0) emissions. Existing studies do not distinguish biotic- and abiotic-mediated emissions and focus only on photoreduction mediated emissions, resulting in an underestimation of soil Hg(0) emissions into the atmosphere. In this study, directional mercury (Hg) reduction pathways in paddy soils were identified using Hg isotopes. Results showed significantly different isotopic compositions of Hg(0) between those produced from photoreduction (δ202Hg = -0.80 ± 0.67‰, Δ199Hg = -0.38 ± 0.18‰), microbial reduction (δ202Hg = -2.18 ± 0.25‰, Δ199Hg = 0.29 ± 0.38‰), and abiotic dark reduction (δ202Hg = -2.31 ± 0.25‰, Δ199Hg = 0.50 ± 0.22‰). Hg(0) exchange fluxes between the atmosphere and the paddy soils were dominated by emissions, with the average flux ranging from 2.2 ± 5.7 to 16.8 ± 21.7 ng m-2 h-1 during different sampling periods. Using an isotopic signature-based ternary mixing model, we revealed that photoreduction is the most important contributor to Hg(0) emissions from paddy soils. Albeit lower, microbial and abiotic dark reduction contributed up to 36 ± 22 and 25 ± 15%, respectively, to Hg(0) emissions on the 110th day. These novel findings can help improve future estimation of soil Hg(0) emissions from rice paddy ecosystems, which involve complex biotic-, abiotic-, and photoreduction processes.

Emission of Intermediate Volatile Organic Compounds from Animal Dung and Coal Combustion and Its Contribution to Secondary Organic Aerosol Formation in Qinghai-Tibet Plateau, China.

Intermediate volatility organic compounds (IVOCs) are important precursors to secondary organic aerosols (SOAs), but they are often neglected in studies concerning SOA formation. This study addresses the significant issue of IVOCs emissions in the Qinghai-Tibetan plateau (QTP), where solid fuels are extensively used under incomplete combustion conditions for residential heating and cooking. Our field measurement data revealed an emission factor of the total IVOCs (EFIVOCs) ranging from 1.56 ± 0.03 to 9.97 ± 3.22 g/kg from various combustion scenarios in QTP. The markedly higher EFIVOCs in QTP than in plain regions can be attributed to oxygen-deficient conditions. IVOCs were dominated by gaseous phase emissions, and the primary contributors of gaseous and particulate phase IVOCs are the unresolved complex mixture and alkanes, respectively. Total IVOCs emissions during the heating and nonheating seasons in QTP were estimated to be 31.7 ± 13.8 and 6.87 ± 0.45 Gg, respectively. The estimated SOA production resulting from combined emissions of IVOCs and VOCs is nearly five times higher than that derived from VOCs alone. Results from this study emphasized the pivotal role of IVOCs emissions in air pollution and provided a foundation for compiling emission inventories related to solid fuel combustion and developing pollution prevention strategies.

Lixisenatide ameliorated lipopolysaccharide (LPS)-induced expression of mucin and inflammation in bronchial epithelial cells.

Chronic obstructive pulmonary disease (COPD) induces serious social and economic burdens due to its high disability and mortality, the pathogenesis of which is highly involved with inflammation, oxidative stress (OS), and mechanism of mucin 5AC (MUC5AC) secretion. Lixisenatide is a selective glucagon-like peptide 1 receptor agonist recently reported to have anti-inflammatory properties. Our study will focus on the potential impact of lixisenatide on lipopolysaccharide (LPS)-induced mucin secretion and inflammation in 16 human bronchial epithelial (16HBE) cells to check its potential function in COPD. 16HBE cells were treated with LPS, with or without lixisenatide (10 and 20 nM) for 1 day. Remarkably declined cell viability, enhanced lactate dehydrogenase release, activated OS, and elevated release of inflammatory cytokines were observed in LPS-treated 16HBE cells, accompanied by the activation of nuclear factor-κB signaling, all of which were signally reversed by lixisenatide. Moreover, elevated expression and release of MUC5AC were observed in LPS-treated 16HBE cells but were markedly repressed by lixisenatide. Furthermore, the repressed nuclear factor erythroid 2-related factor 2 (Nrf2) level in LPS-treated 16HBE cells was notably rescued by lixisenatide. Lastly, following the knockdown of Nrf2, the protective function of lixisenatide on LPS-triggered MUC5AC release in 16HBE cells was significantly abrogated. Collectively, lixisenatide ameliorated LPS-induced expression of mucin and inflammation in bronchial epithelial cells by regulating Nrf2.

Association between left bundle branch block and ventricular septal mid-wall fibrosis in patients with preserved left ventricular ejection fraction.

BACKGROUND: The left bundle branch block (LBBB) is associated with ventricular septal mid-wall fibrosis (SMF) in patients with dilated cardiomyopathy (DCM). However, whether LBBB is also associated with SMF in patients with preserved left ventricular ejection fraction (LVEF) remains unclear. METHODS: We performed a retrospective study of 210 patients with preserved LVEF (male, n = 116; female, n = 94; mean age, 44 ± 17 years). LBBB was defined as QRS duration ≥140 ms for men or ≥ 130 ms for women, QS or rS in V1-V2, mid-QRS notching or slurring in at least two leads (V1, V2, V5, V6, I, and aVL). SMF determined by late gadolinium-enhancement cardiovascular magnetic resonance was defined as stripe-like or patchy mid-myocardial hyper-enhancement in the interventricular septal segments. RESULTS: SMF was detected in 24.8% (52/210) of these patients. The proportion of patients with SMF with LBBB was higher than the proportion of patients with SMF without LBBB (58.3% vs. 20.4%; P < 0.001). In the forward multivariate logistic analysis, LBBB (OR, 4.399; 95% CI, 1.774-10.904; P = 0.001) and age (OR, 1.028; 95% CI, 1.006-1.051; P = 0.011) were independently associated with SMF. The presence of LBBB showed a sensitivity of 27%%, specificity of 94%, positive predictive value of 58%%, and negative predictive value of 80% for the detection of SMF. CONCLUSION: LBBB was significantly associated with SMF in hospitalized patients with preserved LVEF. Screening with a resting 12­lead ECG may help to identify patients who are at a high risk of the presence of SMF.

Using Mercury Stable Isotopes to Quantify Bidirectional Water-Atmosphere Hg(0) Exchange Fluxes and Explore Controlling Factors.

In this study, exchange fluxes and Hg isotope fractionation during water-atmosphere Hg(0) exchange were investigated at three lakes in China. Water-atmosphere exchange was overall characterized by net Hg(0) emissions, with lake-specific mean exchange fluxes ranging from 0.9 to 1.8 ng m-2 h-1, which produced negative δ202Hg (mean: -1.61 to -0.03‰) and Δ199Hg (-0.34 to -0.16‰) values. Emission-controlled experiments conducted using Hg-free air over the water surface at Hongfeng lake (HFL) showed negative δ202Hg and Δ199Hg in Hg(0) emitted from water, and similar values were observed between daytime (mean δ202Hg: -0.95‰, Δ199Hg: -0.25‰) and nighttime (δ202Hg: -1.00‰, Δ199Hg: -0.26‰). Results of the Hg isotope suggest that Hg(0) emission from water is mainly controlled by photochemical Hg(0) production in water. Deposition-controlled experiments at HFL showed that heavier Hg(0) isotopes (mean ε202Hg: -0.38‰) preferentially deposited to water, likely indicating an important role of aqueous Hg(0) oxidation played during the deposition process. A Δ200Hg mixing model showed that lake-specific mean emission fluxes from water surfaces were 2.1-4.1 ng m-2 h-1 and deposition fluxes to water surfaces were 1.2-2.3 ng m-2 h-1 at the three lakes. Results from the this study indicate that atmospheric Hg(0) deposition to water surfaces indeed plays an important role in Hg cycling between atmosphere and water bodies.

Emissions database development and dispersion model predictions of airborne particulate elements in the Canadian Athabasca oil sands region.

This study developed an emission inventory for 29 elements in PM2.5 and PM2.5-10 covering an area of approximately 300 by 420 km2 in the Athabasca Oil Sands Region in northern Alberta, Canada. Emission sources were aggregated into nine categories, of which the Oil Sands (OS) Sources emitted the most, followed by the Non-OS Dust sources for both fine and coarse elements over the study area. The top six fine particulate elements include Si, Ca, Al, Fe, S, and K (933, 442, 323, 269, 116, and 103 tonnes/year, respectively), the sum of which accounted for 20.5% of the total PM2.5 emissions. The top five coarse elements include Si, Ca, Al, Fe, and K (3713, 1815, 1198, 1073, and 404 tonnes/year), and their sum accounted for 29% of the total PM2.5-10 emissions. Using this emission inventory as input, the CALPUFF dispersion model simulated reasonable element concentrations in both PM2.5 and PM2.5-10 when compared to measurements collected at three sites during 2016-2017. Modeled PM10 concentrations of all elements were very close to the measurements at an industrial site with the highest ambient concentration, overestimated by 65% at another industrial site with moderate ambient concentration, and underestimated by 27% at a remote site with very low ambient concentration. Model-measurement differences of annual average concentrations were within 20% for Si, Ca, Al, Fe, Ti, Mn, and Cu in PM2.5, and were 20-50% for K, S, and Zn in PM2.5 at two sites located within the OS surface mineable area. Model-measurement differences were larger, but still within a factor of two for elements in PM2.5-10 at these two sites and for elements in both PM2.5 and PM2.5-10 at a background site.

Percutaneous endoscopic decompression for calcified thoracic disc herniation using a novel T rigid bendable burr.

BACKGROUND: The basic endoscopic instruments are not suitable for removing calcified or hard discs in patients with thoracic disc herniations (TDH). We describe a percutaneous endoscopic technique for the treatment of calcified TDH using an endoscopic drill system with a T rigid bendable burr. METHODS: Eleven patients (8 males, mean age 42.1 years) with single-segmental calcified TDH were treated with percutaneous endoscopic surgeries. RESULTS: Our technique using this endoscopic drill system with a T rigid bendable burr is safe and effective for the treatment of calcified TDH. CONCLUSIONS: Percutaneous endoscopic decompression using the T rigid bendable burr is a safe and reproducible surgical procedure for the treatment of calcified TDH.

Fine particulate pollution driven by nitrate in the moisture urban atmospheric environment in the Pearl River Delta region of south China.

To identify potential sources of fine particles (PM2.5, with aerodynamic diameter (Da) ≤ 2.5 µm) in urban Dongguan of south China, a comprehensive campaign was carried out in the whole 2019. Hourly PM2.5 and its dominant chemical components including organic carbon (OC), elemental carbon (EC), water-soluble inorganic ions (WSIIs) and thirteen elements were measured using online instruments. Gaseous pollutants including NH3, HNO3, NO2, NO and O3 and meteorological parameters were also synchronously measured. PM2.5 was dominated by carbonaceous aerosols in summer and by WSIIs in the other seasons. PM2.5 and its dominant chemical components mostly peaked around noon (10:00-14:00 LST). Furthermore, high PM2.5 levels during the daytime were closely related with the increased NO3- levels. The high mass concentrations of NO3- in urban Dongguan during the daytime were likely related with regional transport of NO3- from suburban Dongguan, which was originated from the reaction between NO2 and O3 under the moisture condition during the nighttime. Seven major source factors for PM2.5 including secondary sulfate, ship emission, traffic emission, secondary nitrate, industrial processes, soil dust and coal combustion were identified by positive matrix factorization (PMF) analysis, which contributed 26 ± 14%, 16 ± 16%, 16 ± 10%, 14 ± 11%, 12 ± 11%, 8 ± 6% and 8 ± 6%, respectively, to annual PM2.5 mass concentration. Although secondary sulfate contributed much more than secondary nitrate to PM2.5 on annual basis, the latter exceeded the former source factor when daily PM2.5 mass concentration was higher than 60 µg m-3, indicating the critical role nitrate played in PM2.5 episode events.

Transport of neonicotinoid insecticides in a wetland ecosystem: Has the cultivation of different crops become the major sources?

Extensive application of neonicotinoid insecticides (NNIs) in agricultural production has resulted in widespread contamination of multiple environmental media. To investigate the occurrence and fate of NNIs in the largest marsh distribution area in Northeast China, an integrated ecosystem covering farmlands, rivers, and marshes, referred to as the farmland-river-marsh continuum in this study, was chosen for soil, water, and sediment sampling. Five NNIs were detected, with imidacloprid (IMI), thiamethoxam (THM), and clothianidin (CLO) being the most frequently detected ones in different samples. Concentrations of target NNIs in soil, surface water, and sediment samples were 2.23-136 ng/g dry weight (dw), 3.20-51.7 ng/L, and 1.53-8.40 ng/g dw, respectively. In soils, NNIs were detected more often and at higher concentrations in upland fields, while the concentration of NNIs in the soybean-growing soils (71.5 ng/g dw) was significantly higher than in the rice-growing soils (18.5 ng/g dw) (p < 0.05). Total concentration of NNIs in surface water was lower in the Qixing River channel than inside the marsh, while that in sediments showed an opposite trend. Total migration mass of IMI from approximately 157,000 ha of farmland soil by surface runoff was estimated to be 2636-3402 kg from the application time to the sampling period. The storage of NNIs in sediments was estimated to range from 45.9 to 252 ng/cm2. The estimated environmental risks, calculated as the risk quotients (RQs), revealed low risks to aquatic organisms (RQs <0.1) from the residual concentrations of NNIs in water.

Seasonal variations of mass absorption efficiency of elemental carbon in PM2.5 in urban Guangzhou of South China.

This study investigates seasonal variations of mass absorption efficiency of elemental carbon (MAEEC) and possible influencing factors in urban Guangzhou of South China. Mass concentrations of elemental carbon (EC) and organic carbon (OC) in PM2.5 and aerosol absorption coefficient (bap) at multi-wavelengths were simultaneously measured in four seasons of 2018-2019 at hourly resolution by a semi-continuous carbon analyzer and an aethalometer. Seasonal average mass concentrations of EC were in the range of 1.36-1.70 µgC/m3 with a lower value in summer than in the other seasons, while those of OC were in the range of 4.70-6.49 µgC/m3 with the lowest value in summer and the highest in autumn. Vehicle exhaust from local traffic was identified to be the predominant source of carbonaceous aerosols. The average aerosol absorption Ångström exponents (AAE) were lower than 1.2 in four seasons, indicating EC and bap were closely related with vehicle exhaust. Seasonal MAEEC at 550 nm was 11.0, 8.5, 10.4 and 11.3 m2/g in spring, summer, autumn, and winter, respectively. High MAEEC was related with the high mass ratio of non-carbonaceous aerosols to EC and high ambient relative humidity.

A database of modeled gridded dry deposition velocities for 45 gaseous species and three particle size ranges across North America.

The dry deposition process refers to the flux loss of an atmospheric pollutant due to uptake of the pollutant by the earth's surfaces. Dry deposition flux of a chemical species is typically calculated as the product of its surface-layer concentration and its dry deposition velocity (Vd). Field measurement based Vd data are very scarce or do not exist for many chemical species considered in chemistry transport models. In the present study, gaseous and particulate dry deposition schemes were applied to generate a database of hourly Vd for 45 gaseous species and three particle size ranges for two years (2016-2017) at a 15 km by 15 km horizontal resolution across North America. Hourly Vd of the 45 gaseous species ranged from < 0.001 to 4.6 cm/sec across the whole domain, with chemical species-dependent median (mean) values being in the range of 0.018-1.37 cm/sec (0.05-1.43 cm/sec). The spatial distributions of the two-year average Vd showed values higher than 1-3 cm/sec for those soluble and reactive species over certain land types. Soluble species have the highest Vd over water surfaces, while insoluble but reactive species have the highest Vd over forests. Hourly Vd of PM2.5 across the whole domain ranged from 0.039 to 0.75 cm/sec with median (mean) value of 0.18 (0.20) cm s-1, while the mean Vd for PM2.5-10 is twice that of PM2.5. Uncertainties in the modeled Vd are typically on the order of a factor of 2.0 or larger, which needs to be considered when applying the dataset in other studies.

pH-Dependent Chemical Transformations of Humic-Like Substances and Further Cognitions Revealed by Optical Methods.

Humic-like substances (HULIS) are macromolecular complex groups in water-soluble organic compounds (WSOC). pH is a crucial factor that influences the chemical transformations of HULIS in atmospheric particles, but this has been rarely investigated, especially under varying pH conditions. This study attempted to unveil the chemical transformation mechanisms of HULIS under a range of pH conditions using optical methods. The pH-dependent light absorption and fluorescence properties of HULIS were comprehensively analyzed; the acidity coefficient (pKa) of HULIS in relation to chemical structures was determined, and the hypothetical chemical transformation mechanisms of HULIS with increasing pH were analyzed by optical characterizations. The results suggested that pH greatly impacted the light absorption and fluorescence efficiencies of HULIS in both winter and summer seasons, and pKa was an important inflection point. The pKa of HULIS ranged from 3.5 to 8.0 in winter and 6.4 to 10.0 in summer. The acidic/basic groups were identified as -OH or -NH2 substituted quinolines, carboxylic aromatics, and pyridines. The pH-sensitive species accounted for about 6% and 21% of HULIS-C (carbon concentrations of HULIS) in winter and summer, respectively. The varying optical spectra with increasing pH might result from charge transfer or complex reactions with HULIS deprotonation.

Sources and Transformation Mechanisms of Atmospheric Particulate Bound Mercury Revealed by Mercury Stable Isotopes.

This study examined the isotopic composition of particulate bound mercury (PBM) in 10 Chinese megacities and explored the associated sources and transformation mechanisms. PBM in these cities was characterized by negative δ202Hg (mean: -2.00 to -0.78‰), slightly negative to highly positive Δ199Hg (mean: -0.04 to 0.47‰), and slightly positive Δ200Hg (mean: 0.02 to 0.06‰) values. The positive PBM Δ199Hg signatures were likely caused by physiochemical reactions in aerosols. The Δ199Hg/Δ201Hg ratio varied from 0.94 to 1.39 in the cities and increased with the increase in the corresponding mean Δ199HgPBM value. We speculate that, in addition to the photoreduction of oxidized Hg, other transformation mechanisms in aerosols (e.g., isotope exchange, complexation, and oxidation, which express nuclear volume effects) also shape the Δ199HgPBM signatures in the present study. These processes are likely enhanced in the presence of strong gas-particle partitioning of gaseous oxidized Hg (GOM) and elevated levels of redox active metals (e.g., Fe), halides, and elemental carbon. Based on Δ200HgPBM data presented in this and previous studies, we estimate that large proportions (∼47 ± 22%) of PBM were sourced from the oxidation of gaseous elemental Hg followed by the partitioning of GOM onto aerosols globally, indicating the transformation of Hg(0) to PBM as an important sink of atmospheric Hg(0).

Source apportionment of carbonaceous aerosols using hourly data and implications for reducing PM2.5 in the Pearl River Delta region of South China.

Ambient fine particulate matter (PM2.5) levels in South China have been decreasing in the past decade, but the decreasing rates differed between its major chemical components, e.g., with much small rates for carbonaceous aerosols than for secondary inorganic aerosols. To investigate the sources of carbonaceous aerosols in this region, a comprehensive campaign was carried out in urban Guangzhou in the winter of 2019-2020 using a combination of various instruments. Data generated from this campaign include hourly total carbon (TC), black carbon (BC), criteria air pollutants and meteorological parameters, 4-hourly particle-bound elements, and chemically-resolved daily PM2.5. Similar diurnal patterns were observed for TC, CO and NO2, suggesting TC was very likely related to vehicle exhaust emission. Secondary organic carbon (SOC) estimated using the Minimum R squared (MRS) method accounted for 35 ± 17% of OC, indicating strong atmospheric oxidation capacity. Four major source factors for carbonaceous aerosols were identified by positive matrix factorization (PMF) model, including coal combustion, traffic emissions, soil dust and ship emissions, which accounted for 37 ± 23%, 39 ± 23%, 14 ± 10% and 10 ± 13%, respectively, of TC mass concentration, 38 ± 24%, 38 ± 23%, 14 ± 10% and 10 ± 12%, respectively, of OC mass concentration, and 29 ± 21%, 43 ± 22%, 14 ± 11% and 14 ± 15%, respectively, of EC mass concentration. Among these sources, traffic emission was the most important one, suggesting the necessity for promoting clean energy vehicles and relieving urban traffic congestion.

Association between complete right bundle branch block and atrial fibrillation development.

BACKGROUND: Complete right bundle branch block (CRBBB) is an important predictor of atrial fibrillation (AF) recurrence after pulmonary vein isolation. However, the association between CRBBB and AF development remains unclear. METHODS: We performed a retrospective study of 2639 patients (male, n = 1549; female, n = 1090; mean age, 58 ± 13 years). CRBBB was defined as a late R (R') wave in lead V1 or V2 with a slurred S wave in lead I and/or lead V6 with a prolonged QRS duration (≥120 ms). RESULTS: Among the 2639 patients, CRBBB was detected in 40 patients (1.5%), and the prevalence of AF was 7.4% (196/2639). The proportion of patients with AF and CRBBB was higher than the proportion of patients with AF without CRBBB (22.5% vs. 7.2%; p = 0.001). In the forward multivariate logistic analysis, CRBBB (odds ratio [OR], 3.329; 95% confidence interval [CI], 1.350-8.211; p = 0.009), complete left bundle branch block (OR, 2.209; 95% CI, 1.238-3.940; p = 0.007), age (OR, 1.020; 95% CI, 1.005-1.035; p = 0.009), valvular heart disease (OR, 2.332; 95% CI, 1.531-3.552; p < 0.001), left atrial diameter (OR, 1.133; 95% CI, 1.104-1.163; p < 0.001), left ventricular ejection fraction (OR, 1.023; 95% CI, 1.006-1.041; p = 0.007), and class I or III anti-arrhythmic drug use (OR, 10.534; 95% CI, 7.090-15.651; p < 0.001) were associated with AF. CONCLUSION: Complete right bundle branch block was significantly associated with AF development in hospitalized patients with cardiovascular diseases.

Clarifying winter clean heating importance: Insight chemical compositions and cytotoxicity exposure to primary and aged pollution emissions in China rural areas.

Residential solid fuel combustion (RSFC) is an important source of PM2.5. Here we investigate the cytotoxicity of primarily emitted and photochemically aged PM2.5 to A549 cells. Owing to the formation of water-soluble ions and organics (e.g., oPAHs and nPAHs), emission factors of PM2.5 were increased by 44.4% on average after 7-day equivalent photochemical aging, which greatly altered chemical profiles of freshly emitted PM2.5. Consequently, the cytotoxicity varied with aging duration that 2-day and 7-day aged PM2.5 induced 22.5% and 35.1%, respectively, higher levels of reactive oxygen species than primary emissions. Similar increases were also observed for multi-cytotoxicity. Correlation analysis and western blot results collectively confirmed HO-1/Nrf-2 signaling pathway dominated the cytotoxicity of aged PM2.5 from RSFC, which was regulated by the enhanced o-PAHs and n-PAHs during photochemical aging. Thus, aged and secondary aerosol exposure needs to be paid more attention due to the enhanced cytotoxicity and the vast crowd involved.

PU.1 inhibition attenuates atrial fibrosis and atrial fibrillation vulnerability induced by angiotensin-II by reducing TGF-ß1/Smads pathway activation.

Fibrosis serves a critical role in driving atrial remodelling-mediated atrial fibrillation (AF). Abnormal levels of the transcription factor PU.1, a key regulator of fibrosis, are associated with cardiac injury and dysfunction following acute viral myocarditis. However, the role of PU.1 in atrial fibrosis and vulnerability to AF remain unclear. Here, an in vivo atrial fibrosis model was developed by the continuous infusion of C57 mice with subcutaneous Ang-II, while the in vitro model comprised atrial fibroblasts that were isolated and cultured. The expression of PU.1 was significantly up-regulated in the Ang-II-induced group compared with the sham/control group in vivo and in vitro. Moreover, protein expression along the TGF-ß1/Smads pathway and the proliferation and differentiation of atrial fibroblasts induced by Ang-II were significantly higher in the Ang-II-induced group than in the sham/control group. These effects were attenuated by exposure to DB1976, a PU.1 inhibitor, both in vivo and in vitro. Importantly, in vitro treatment with small interfering RNA against Smad3 (key protein of TGF-ß1/Smads signalling pathway) diminished these Ang-II-mediated effects, and the si-Smad3-mediated effects were, in turn, antagonized by the addition of a PU.1-overexpression adenoviral vector. Finally, PU.1 inhibition reduced the atrial fibrosis induced by Ang-II and attenuated vulnerability to AF, at least in part through the TGF-ß1/Smads pathway. Overall, the study implicates PU.1 as a potential therapeutic target to inhibit Ang-II-induced atrial fibrosis and vulnerability to AF.

Compound-Specific Stable Isotope Analysis Provides New Insights for Tracking Human Monomethylmercury Exposure Sources.

Monomethylmercury (MMHg) exposure can induce adverse neurodevelopmental effects in humans and is a global environmental health concern. Human exposure to MMHg occurs predominately through the consumption of fishery foods and rice in Asia, but it is challenging to quantify these two exposure sources. Here, we innovatively utilized MMHg compound-specific stable isotope analyses (MMHg-CSIA) of the hair to quantify the human MMHg sources in coastal and inland areas, where fishery foods and rice are routinely consumed. Our data showed that the fishery foods and rice end members had distinct Δ199HgMMHg values in both coastal and inland areas. The Δ199HgMMHg values of the human hair were comparable to those of fishery foods but not those of rice. Positive shifts in the δ202HgMMHg values of the hair from diet were observed in the study areas. Additionally, significant differences in δ202Hg versus Δ199Hg were detected between MMHg and inorganic Hg (IHg) in the human hair but not in fishery foods and rice. A binary mixing model was developed to estimate the human MMHg exposures from fishery foods and rice using Δ199HgMMHg data. The model results suggested that human MMHg exposures were dominated (>80%) by fishery food consumption and were less affected by rice consumption in both the coastal and inland areas. This study demonstrated that the MMHg-CSIA method can provide unique information for tracking human MMHg exposure sources by excluding the deviations from dietary surveys, individual MMHg absorption/demethylation efficiencies, and the confounding effects of IHg.

Effect of catheter ablation on clinical outcomes in patients with atrial fibrillation and significant functional mitral regurgitation.

BACKGROUND: In patients with atrial fibrillation (AF) and functional mitral regurgitation (MR), catheter ablation reduces the severity of MR and improves cardiac remodeling. However, its effects on prognosis are uncertain. METHODS: This retrospective study included 151 consecutive patients with AF and functional MR, 82 (54.3%) of whom were treated by catheter ablation (Ablation group) and 69 (45.7%) with drug therapy without ablation (Non-ablation group). Forty-three pairs of these patients were propensity matched on the basis of age, CHA2DS2-VASc scores, and left ventricular ejection fraction. The primary outcome evaluated was severity of MR, cardiac remodeling and the combined incidence of subsequent heart failure-related hospitalization and strokes/transient ischemic attacks. RESULTS: Patients in the Ablation group showed a significant decrease in the severity of MR (p < 0.001), a significant decrease in the left atrial diameter (p = 0.010), and significant improvement in the left ventricular ejection fraction (p = 0.015). However, patients in the Non-ablation group showed only a significant decrease in the severity of MR (p = 0.004). The annual incidence of the studied events was 4.9% in the Ablation group and 16.7% in the Non-ablation group, the incidence being significantly lower in the ablation than Non-ablation group (p = 0.026) according to Kaplan-Meier curve analyses. According to multivariate Cox regression analysis, catheter ablation therapy (hazard ratio [HR] 0.27, 95% confidence interval [CI] 0.09-0.84; p = 0.024) and heart failure at baseline (HR 3.84, 95% CI 1.07-13.74; p = 0.038) were independent predictors of the incidence of the studied events. CONCLUSIONS: Among patients with AF and functional MR, catheter ablation was associated with a significantly lower combined risk of heart failure-related hospitalization and stroke than in a matched cohort of patients receiving drug therapy alone.