Pollution Level and Health Risk Assessment of PM2.5-Bound Metals in Baoding City Before and After the Heating Period.

In order to assess the pollution levels and health risks of PM2.5-bound metals in Baoding City before and after the heating period, samples were collected in 2016 at Hebei University from September 25th to November 14th during the non-heating period, and November 15th to December 26th during the heating period, respectively. ICP-MS was applied to analyze seven heavy metals (Cr, Zn, Cu, Pb, Ni, Cd and Fe). The statistical analysis, enrichment factor (EF), pollution load index method, and Risk Assessment Method proposed by U.S. EPA were used to evaluate the non-carcinogenic risks of six of these heavy metals (Cr, Zn, Cu, Pb, Ni and Cd) and carcinogenic risks of three of these heavy metals (Cr, Ni and Cd). The results showed three main results. First, the average daily PM2.5 concentrations of the national air monitoring stations was 155.66 µg·m-3 which was 2.08 times as high as that of the second level criterion in China (75 µg·m-3) during the observation period. Compared with the non-heating period, all heavy metals concentrations increased during heating period. The growth rates of Pb and Ni were the highest and the lowest, which were 88.03 and 5.11 percent, respectively. Second, the results of enrichment factor indicated that the EF values of all heavy metals were higher during the heating period in comparison with during the non-heating period, but the degree of enrichment of all heavy metals remained unchanged. Not only those, Cr and Ni were minimally enriched and were affected by both human and natural factors, Pb, Cu and Zn were significantly enriched and were mainly affected by human factors, the enrichment of Cd was much higher than that of the other heavy metals, exhibiting extremely high enrichment, mainly due to human factors during the whole sampling period. The results of the pollution load index indicated that the proportions of the number of highly and very highly polluted PM2.5-bound metals were the highest during the heating period, while the proportion of moderately polluted PM2.5-bound metals was the highest during the non-heating period. The combined pollution degree of heavy metals was more serious during the heating period. Third, according to the health risk assessment model, we concluded that the non-carcinogenic and carcinogenic risks caused by inhalation exposure were the highest and by dermal exposure were the lowest for all kinds of people. The overall non-carcinogenic risk of heavy metals via inhalation and subsequent ingestion exposure caused significant harm to children during the non-heating and the heating periods, and the risk values were 2.64, 4.47, 1.20 and 1.47, respectively. Pb and Cr exhibited the biggest contributions to the non-carcinogenic risk. All the above non-carcinogenic risks exceeded the standard limits suggested by EPA (HI or HQ < 1). The carcinogenic risk via inhalation exposure to children, adult men and women were 2.10 × 10-4, 1.80 × 10-4, and 1.03 × 10-4 during the non-heating period, respectively, and 2.52 × 10-4, 2.16 × 10-4 and 1.23 × 10-4 during the heating period, respectively. All the above carcinogenic risks exceeded the threshold ranges (10-6~10-4), and Cr posed a carcinogenic risk to all people.

Analysis of the Characteristics and Sources of Carbonaceous Aerosols in PM2.5 in the Beijing, Tianjin, and Langfang Region, China.

PM2.5 samples from Beijing, Tianjin, and Langfang were simultaneously collected from 20 November 2016 to 25 December 2016, and the organic carbon (OC) and elemental carbon (EC) content in the samples were measured and analyzed. The pollution characteristics and sources of OC and EC in atmospheric PM2.5 for three adjacent cities were discussed. The average mass concentrations of OC in PM2.5 in Beijing, Tianjin, and Langfang were 27.93 ± 23.35 µg/m³, 25.27 ± 12.43 µg/m³, and 52.75 ± 37.97 µg/m³, respectively, and the mean mass concentrations of EC were 6.61 ± 5.13 µg/m³, 6.14 ± 2.84 µg/m³, and 12.06 ± 6.81 µg/m³, respectively. The average mass concentration of total carbon (TC) accounted for 30.5%, 24.8%, and 49% of the average mass concentration of PM2.5 in the atmosphere. The total carbonaceous matter (TCA) in Beijing, Tianjin, and Langfang was 51.29, 46.57, and 96.45 µg/m³, respectively. The TCA was the main component of PM2.5 in the region. The correlation between OC and EC in the three cities showed R² values of 0.882, 0.633, and 0.784 for Beijing, Tianjin, and Langfang, respectively, indicating that the sources of urban carbonaceous aerosols had good consistency and stability. The OC/EC values of the three sampling points were 4.48 ± 1.45, 4.42 ± 1.77, and 4.22 ± 1.29, respectively, considerably greater than 2, indicating that the main sources of pollution were automobile exhaust, and the combustion of coal and biomass. The OC/EC minimum ratio method was used to estimate the secondary organic carbon (SOC) content in Beijing, Tianjin and Langfang. Their values were 10.73, 10.71, and 19.51, respectively, which accounted for 38%, 42%, and 37% of the average OC concentration in each city, respectively. The analysis of the eight carbon components showed that the main sources of pollutants in Beijing, Tianjin, and Langfang were exhaust emissions from gasoline vehicles, but the combustion of coal and biomass was relatively low. The pollution of road dust was more serious in Tianjin than in Beijing and Langfang. The contribution of biomass burning and coal-burning pollution sources to atmospheric carbon aerosols in Langfang was more prominent than that of Beijing and Tianjin.

TRPV4 (Transient Receptor Potential Vanilloid 4) Mediates Endothelium-Dependent Contractions in the Aortas of Hypertensive Mice.

The role of TRPV4 (transient receptor potential vanilloid 4) in regulating vascular contraction in hypertensive mice is poorly established. We tested the hypothesis that TRPV4 regulates endothelium-dependent contractions in aortas from hypertensive mice through the activation of cytosolic cPLA2 (phospholipase A2) and COX2 (cyclooxygenase 2) and identified the possible endothelium-derived contracting factor generated by COX2. Using myography, we demonstrated that GSK1016790A (a TRPV4 agonist) and acetylcholine (ACh) trigger endothelium-dependent contractions in aortas from hypertensive mice, and the contractions were abolished with TRPV4 deletion. PLA2 assay and Western blotting showed that cPLA2 activity was higher in salt-induced hypertension and HC067047 or a Ca2+ chelator inhibited cPLA2 activity. Contractions induced by TRPV4 and ACh were inhibited by the cPLA2 inhibitor or removal of extracellular Ca2+ COX2 expression was enhanced in the endothelium from hypertensive mice and contractions induced by TRPV4 or ACh were inhibited by the COX2 inhibitor. Enzyme immunoassay showed that the release of prostaglandin F2α (PGF2α) was increased in hypertensive mice. GSK1016790A or ACh triggered the release of PGF2α and this was inhibited by HC067047, the cPLA2 inhibitor, and COX2 inhibitor. GSK1016790A, ACh, and PGF2α induced contractions were significantly reduced by S18886 in salt-induced hypertensive mice. The present study demonstrates that PGF2α generated by COX2 in the endothelium is the most likely endothelium-derived contracting factor underlying endothelium-dependent, TRPV4-mediated contraction in hypertensive mice. This contraction involved increased intracellular Ca2+ concentrations and cPLA2 activity. These results suggested an important role of TRPV4 in endothelium-dependent contraction in mice during hypertension.

Treatment of hypertension by increasing impaired endothelial TRPV4-KCa2.3 interaction.

The currently available antihypertensive agents have undesirable adverse effects due to systemically altering target activity including receptors, channels, and enzymes. These effects, such as loss of potassium ions induced by diuretics, bronchospasm by beta-blockers, constipation by Ca2+ channel blockers, and dry cough by ACEI, lead to non-compliance with therapies (Moser, 1990). Here, based on new hypertension mechanisms, we explored a new antihypertensive approach. We report that transient receptor potential vanilloid 4 (TRPV4) interacts with Ca2+-activated potassium channel 3 (KCa2.3) in endothelial cells (ECs) from small resistance arteries of normotensive humans, while ECs from hypertensive patients show a reduced interaction between TRPV4 and KCa2.3. Murine hypertension models, induced by high-salt diet, N(G)-nitro-l-arginine intake, or angiotensin II delivery, showed decreased TRPV4-KCa2.3 interaction in ECs. Perturbation of the TRPV4-KCa2.3 interaction in mouse ECs by overexpressing full-length KCa2.3 or defective KCa2.3 had hypotensive or hypertensive effects, respectively. Next, we developed a small-molecule drug, JNc-440, which showed affinity for both TRPV4 and KCa2.3. JNc-440 significantly strengthened the TRPV4-KCa2.3 interaction in ECs, enhanced vasodilation, and exerted antihypertensive effects in mice. Importantly, JNc-440 specifically targeted the impaired TRPV4-KCa2.3 interaction in ECs but did not systemically activate TRPV4 and KCa2.3. Together, our data highlight the importance of impaired endothelial TRPV4-KCa2.3 coupling in the progression of hypertension and suggest a novel approach for antihypertensive drug development.

Spatial Distribution, Sources Apportionment and Health Risk of Metals in Topsoil in Beijing, China.

In order to acquire the pollution feature and regularities of distribution of metals in the topsoil within the sixth ring road in Beijing, a total of 46 soil samples were collected, and the concentrations of twelve elements (Nickel, Ni, Lithium, Li, Vanadium, V, Cobalt, Co, Barium, Ba, Strontium, Sr, Chrome, Cr, Molybdenum, Mo, Copper, Cu, Cadmium, Cd, Zinc, Zn, Lead, Pb) were analyzed. Geostatistics and multivariate statistics were conducted to identify spatial distribution characteristics and sources. In addition, the health risk of the analyzed heavy metals to humans (adult) was evaluated by an U.S. Environmental Protection Agency health risk assessment model. The results indicate that these metals have notable variation in spatial scale. The concentration of Cr was high in the west and low in the east, while that of Mo was high in the north and low in the south. High concentrations of Cu, Cd, Zn, and Pb were found in the central part of the city. The average enrichment degree of Cd is 5.94, reaching the standard of significant enrichment. The accumulation of Cr, Mo, Cu, Cd, Zn, and Pb is influenced by anthropogenic activity, including vehicle exhaustion, coal burning, and industrial processes. Health risk assessment shows that both non-carcinogenic and carcinogenic risks of selected heavy metals are within the safety standard and the rank of the carcinogenic risk of the four heavy metals is Cr > Co > Ni > Cd.

Translocation of PKG1α acts on TRPV4-C1 heteromeric channels to inhibit endothelial Ca(2+) entry.

AIM: TRPV4-C1 heteromeric channels contribute to store-operated Ca(2+) entry in vascular endothelial cells. However, the negative regulation of these channels is not fully understood. This study was conducted to investigate the inhibitory effect of PKG1α on TRPV4-C1 heteromeric channels. METHODS: Immuno-fluorescence resonance energy transfer (FRET) was used to explore the spatial proximity of PKG1α and TRPC1. Phosphorylation of endogenous TRPC1 was tested by phosphorylation assay. [Ca(2+)]i transients and cation current in MAECs were assessed with Fura-2 fluorescence and whole-cell recording, respectively. In addition, rat mesenteric arteries segments were prepared, and vascular relaxation was examined with wire myography. RESULTS: In immuno-FRET experiments, after exposure of these cells to 8-Br-cGMP, more PKG1α was observed in the plasma membrane, and PKG1α and TRPC1 were observed to be in closer proximity. TAT-TRPC1(S172) and TAT-TRPC1(T313) peptide fragments, which contain the PKG targeted residues Ser172 and Thr313, respectively, were introduced into isolated endothelial cells to abrogate the translocation of PKG1α. Furthermore, a phosphorylation assay demonstrated that PKG directly phosphorylates TRPC1 at Ser172 and Thr313 in endothelial cells. In addition, PKG activator 8-Br-cGMP markedly reduced the magnitude of the 4αPDD-induced and 11,12-EET-induced [Ca(2+)]i transients, the cation current and vascular relaxation. CONCLUSION: This study uncovers a novel mechanism by which PKG negatively regulates endothelial heteromeric TRPV4-C1 channels through increasing the spatial proximity of TRPV4-C1 to PKG1α via translocation and through phosphorylating Ser172 and Thr313 of TRPC1.