Association and mediation analyses among multiple metal exposure, mineralocorticoid levels, and serum ion balance in residents of northwest China.

Toxic metals are vital risk factors affecting serum ion balance; however, the effect of their co-exposure on serum ions and the underlying mechanism remain unclear. We assessed the correlations of single metal and mixed metals with serum ion levels, and the mediating effects of mineralocorticoids by investigating toxic metal concentrations in the blood, as well as the levels of representative mineralocorticoids, such as deoxycorticosterone (DOC), and serum ions in 471 participants from the Dongdagou-Xinglong cohort. In the single-exposure model, sodium and chloride levels were positively correlated with arsenic, selenium, cadmium, and lead levels and negatively correlated with zinc levels, whereas potassium and iron levels and the anion gap were positively correlated with zinc levels and negatively correlated with selenium, cadmium and lead levels (all P < 0.05). Similar results were obtained in the mixed exposure models considering all metals, and the major contributions of cadmium, lead, arsenic, and selenium were highlighted. Significant dose-response relationships were detected between levels of serum DOC and toxic metals and serum ions. Mediation analysis showed that serum DOC partially mediated the relationship of metals (especially mixed metals) with serum iron and anion gap by 8.3% and 8.6%, respectively. These findings suggest that single and mixed metal exposure interferes with the homeostasis of serum mineralocorticoids, which is also related to altered serum ion levels. Furthermore, serum DOC may remarkably affect toxic metal-related serum ion disturbances, providing clues for further study of health risks associated with these toxic metals.

Integrated Transcriptomics and Metabolomics Analysis Reveals the Effects of Cutting on the Synthesis of Flavonoids and Saponins in Chinese Herbal Medicine Astragalus mongholious.

Astragali Radix, derived from the roots of Astragalus mongholicus, is a traditional Chinese medicine containing flavonoids and saponins as its key ingredients. With a shortage in the wild sources of the herbal plant, it is especially important to explore a cultivation mode for A. mongholicus for medicinal purposes. Cutting, a physical environmental stress method, was used in this study with the objective of improving the quality of this herbal legume. We found that cutting of the top 1/3 of the aboveground part of A. mongholicus during the fruiting period resulted in a significant increase in the content of flavonoids and saponins, as well as in root growth, including length, diameter, and dry weight. Furthermore, the leaves were sampled and analyzed using a combined transcriptome and metabolome analysis approach at five different time points after the treatment. Sixteen differentially expressed unigenes (DEGs) involved in the biosynthesis of flavonoids were identified; these were found to stimulate the synthesis of flavonoids such as formononetin and calycosin-7-O-ß-D-glucoside. Moreover, we identified 10 DEGs that were associated with the biosynthesis of saponins, including astragaloside IV and soyasaponin I, and found that they only regulated the mevalonic acid (MVA) pathway. These findings provide new insights into cultivating high-quality A. mongholicus, which could potentially alleviate the scarcity of this valuable medicinal plant.

Heavy metal contamination impacts the structure and co-occurrence patterns of bacterial communities in agricultural soils.

Heavy metal (HM) contamination caused by mining and smelting activities can be harmful to soil microbiota, which are highly sensitive to HM stress. Here, we explore the effects of HM contamination on the taxonomic composition, predicted function, and co-occurrence patterns of soil bacterial communities in two agricultural fields with contrasting levels of soil HMs (i.e., contaminated and uncontaminated natural areas). Our results indicate that HM contamination does not significantly influence soil bacterial α diversity but changes the bacterial community composition by enriching the phyla Gemmatimonadetes, Planctomycetes, and Parcubacteria and reducing the relative abundance of Actinobacteria. Our results further demonstrate that HM contamination can strengthen the complexity and modularity of the bacterial co-occurrence network but weaken positive interactions between keystone taxa, leading to the gradual disappearance of some taxa that originally played an important role in healthy soil, thereby possibly reducing the resistance of bacterial communities to HM toxicity. The predicted functions of bacterial communities are related to membrane transport, amino acid metabolism, energy metabolism, and carbohydrate metabolism. Among these, functions related to HM detoxification and antioxidation are enriched in uncontaminated soils, while HM contamination enriches functions related to metal resistance. This study demonstrated that microorganisms adapt to the stress of HM pollution by adjusting their composition and enhancing their network complexity and potential ecological functions.

Ecological and health risk assessment of heavy metals in agricultural soils from northern China.

Soil pollution by heavy metals can cause continuing damage to ecosystems and the human body. In this study, we collected nine fresh topsoil samples and 18 maize samples (including nine leaf samples and nine corn samples) from agricultural soils in the Baiyin mining areas. The results showed that the order of heavy metal concentrations (mg/kg) in agricultural soils was as follows: Zn (377.40) > Pb (125.06) > Cu (75.06) > Ni (28.29) > Cd (5.46) > Hg (0.37). Cd, Cu, Zn, and Pb exceeded the Chinese risk limit for agricultural soil pollution. The average the pollution load index (4.39) was greater than 3, indicating a heavy contamination level. The element that contributed the most to contamination and high ecological risk in soil was Cd. Principal component analysis (PCA) and Pearson's correlation analysis indicated that the sources of Ni, Cd, Cu, and Zn in the soil were primarily mixed, involving both industrial and agricultural activities, whereas the sources of Hg and Pb included both industrial and transportation activities. Adults and children are not likely to experience non-carcinogenic impacts from the soil in this region. Nonetheless, it was important to be aware of the elevated cancer risk presented by Cd, Pb, and especially Ni. The exceedance rates of Cd and Pb in corn were 66.67% and 33.3%, respectively. The results of this research provide data to improve soil protection, human health monitoring, and crop management in the Baiyin district.

Effects of long-term metal exposure on the structure and co-occurrence patterns of the oral microbiota of residents around a mining area.

Objectives: The aim of our study was to investigate the impact of long-term exposure to heavy metals on the microbiome of the buccal mucosa, to unveil the link between environmental contamination and the oral microbial ecosystem, and to comprehend its potential health implications. Methods: Subjects were divided into two groups: the exposure group and the control group. We collected samples of buccal mucosa, soil, and blood, and conducted microbial diversity analysis on both groups of oral samples using 16S rRNA gene sequencing. The concentrations of heavy metals in blood and soil samples were also determined. Additionally, microbial networks were constructed for the purpose of topological analysis. Results: Due to long-term exposure to heavy metals, the relative abundance of Rhodococcus, Delftia, Fusobacterium, and Peptostreptococcus increased, while the abundance of Streptococcus, Gemella, Prevotella, Granulicatella, and Porphyromonas decreased. The concentrations of heavy metals in the blood (Pb, Cd, Hg, and Mo) were associated with the growth of Rhodococcus, Delftia, Porphyromonas, and Gemella. In addition, the relative abundances of some pathogenic bacteria, such as Streptococcus anginosus, S. gordonii, and S. mutans, were found to be enriched in the exposure group. Compared to the exposure group network, the control group network had a greater number of nodes, modules, interactive species, and keystone taxa. Module hubs and connectors in the control group converted into peripherals in the exposure group, indicating that keystone taxa changed. Metals in the blood (Pb, Cd, Hg, and Mo) were drivers of the microbial network of the buccal mucosa, which can have adverse effects on the network, thus providing conditions for the occurrence of certain diseases. Conclusion: Long-term exposure to multiple metals perturbs normal bacterial communities in the buccal mucosa of residents in contaminated areas. This exposure reduces the complexity and stability of the microbial network and increases the risk of developing various diseases.

Screening of high-efficiency nitrogen-fixing bacteria from the traditional Chinese medicine plant Astragalus mongolicus and its effect on plant growth promotion and bacterial communities in the rhizosphere.

BACKGROUND: Astragalus mongolicus Bunge is used in traditional Chinese medicine and is thus cultivated in bulk. The cultivation of A. mongolicus requires a large amount of nitrogen fertilizer, increasing the planting cost of medicinal materials and polluting the environment. Isolation and screening of plant growth-promoting rhizobacteria (PGPR) and exploring the nitrogen fixation potential of A. mongolicus rhizosphere microorganisms would effectively reduce the production cost of A. mongolicus. RESULTS: This study used A. mongolicus roots and rhizosphere soil samples from Longxi County of Gansu Province, Jingle County, and Hunyuan County of Shanxi Province, China, to isolate and identify nitrogen-fixing bacteria. Through nitrogen fixation efficiency test, single strain inoculation test, and plant growth-promoting characteristics, three strains, Bacillus sp. J1, Arthrobacter sp. J2, and Bacillus sp. G4 were selected from 86 strains of potential nitrogen-fixing bacteria, which were the most effective in promoting the A. mongolicus growth and increasing the nitrogen, phosphorus, and potassium content in plants. The antagonistic test showed that these bacteria could grow smoothly under the co-culture conditions. The J1, J2, and G4 strains were used in a mixed inoculum and found to enhance the biomass of A. mongolicus plants and the accumulation of the main medicinal components in the field experiment. Mixed bacterial agent inoculation also increased bacterial diversity and changed the structure of the bacterial community in rhizosphere soil. Meanwhile, the relative abundance of Proteobacteria increased significantly after inoculation, suggesting that Proteobacteria play an important role in plant growth promotion. CONCLUSIONS: These findings indicate that specific and efficient PGPRs have a significant promoting effect on the growth of A. mongolicus, while also having a positive impact on the structure of the host rhizosphere bacteria community. This study provides a basis for developing a nitrogen-fixing bacterial fertilizer and improving the ecological planting efficiency of A. mongolicus.

The association between multi-heavy metals exposure and lung function in a typical rural population of Northwest China.

BACKGROUND: Heavy metal exposure is acknowledged to be associated with decrease of lung function, but the relationship between metals co-exposure and lung function in rural areas of Northwest China remains unclear, particularly in an area famous for heavy metal pollution and solid fuel use. Therefore, the purpose of this study is to explore the effects of heavy metal exposure on lung function and the potential impacts of living habit in a rural cohort of Northwest China. METHODS: The study area included five villages of two regions in Northwestern China-Gansu province. All participants were recruited from the Dongdagou-Xinglong (DDG-XL) rural cohort in the study area. Urine levels of 10 common and representative heavy metals were detected by ICP-MS, including Cobalt (Co), Nickel (Ni), Molybdenum (Mo), Cadmium (Cd), Stibium (Sb), Copper (Cu), Zinc (Zn), Mercury (Hg), Lead (Pb), and Manganese (Mn). The lung function was detected by measuring percentages of predicted forced vital capacity (FVC%) and predicted forced expiratory volume in one second (FEV1%) as well as the ratio of FEV1/FVC. We also analyzed the association between heavy metals and pulmonary ventilation dysfunction (PVD). Restricted cubic spline, logistic regression, linear regression, and bayesian kernel machine regression (BKMR) model were used to analyze the relationship between heavy metal exposure and lung function. RESULTS: Finally, a total of 382 participants were included in this study with an average age of 56.69 ± 7.32 years, and 82.46% of them used solid fuels for heating and cooking. Single metal exposure analysis showed that the higher concentration of Hg, Mn, Sb, and lower Mo may be risk factors for PVD. We also found that FEV1% and FVC% were negatively correlated with Sb, Hg, and Mn, but positively correlated with Mo. The effect of mixed heavy metals exposure could be observed through BKMR model, through which we found the lung function decreased with the increase of heavy metal concentration. Furthermore, the males, BMI ≥ 24 kg/m2 and who used solid fuels showed a higher risk of PVD when exposed to Co, Zn, and Hg. CONCLUSIONS: Our results suggested that heavy metal exposure was associated with decrease of lung function regardless of single exposure or mixed exposure, particularly for Sb, Hg, Mn and those who use solid fuels.

3-Hydroxy-3-methylglutaryl coenzyme A reductase genes from Glycine max regulate plant growth and isoprenoid biosynthesis.

Isoprenoids, a large kind of plant natural products, are synthesized by the mevalonate (MVA) pathway in the cytoplasm and the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway in plastids. As one of the rate-limiting enzymes in the MVA pathway of soybean (Glycine max), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) is encoded by eight isogenes (GmHMGR1-GmHMGR8). To begin, we used lovastatin (LOV), a specific inhibitor of GmHMGR, to investigate their role in soybean development. To further investigate, we overexpressed the GmHMGR4 and GmHMGR6 genes in Arabidopsis thaliana. The growth of soybean seedlings, especially the development of lateral roots, was inhibited after LOV treatment, accompanied by a decrease in sterols content and GmHMGR gene expression. After the overexpression of GmHMGR4 and GmHMGR6 in A. thaliana, the primary root length was higher than the wild type, and total sterol and squalene contents were significantly increased. In addition, we detected a significant increase in the product tocopherol from the MEP pathway. These results further support the fact that GmHMGR1-GmHMGR8 play a key role in soybean development and isoprenoid biosynthesis.

Effects of cadmium and lead co-exposure on glucocorticoid levels in rural residents of northwest China.

Cadmium (Cd) and lead (Pb) are important environmental endocrine disruptors that are associated with adverse health problems. However, the effects of co-exposure to Cd and Pb on glucocorticoids (GCs) in the body at environmental levels are limited. A total of 468 subjects from the Dongdagou-Xinglong cohort (DDG-XL) were included in this study. We measured the serum levels of two representative endogenous GCs [cortisol (CRL) and cortisone (CRN)], and whole blood levels of Cd and Pb. Multiple linear regression models were constructed to explore the associations of single or combined Cd and Pb exposure with serum CRL and CRN levels. The interactive effects of Cd and Pb on GCs were further assessed using mediation analysis and moderation analysis. Single-heavy metal exposure analysis with adjustment for potential confounders showed that the serum CRL level decreased when the blood Cd or Pb concentration gradually increased (P trend <0.01). Additionally, subjects with high Cd or Pb exposure (Q4) had significantly reduced serum CRN levels compared to those with low Cd or Pb exposure (Q1) (P < 0.05). In Cd and Pb co-exposure analysis, significant negative dose-response relationships were observed between co-exposure to Cd and Pb and serum CRL and CRN levels. Furthermore, mediation analysis showed that Cd completely mediated the relationship between Pb and GCs, and moderation analysis suggested that Pb might weaken the negative relationship between Cd and GCs. These findings suggest that single or combined exposure to Cd and Pb interferes with the homeostasis of serum CRL and CRN levels. Furthermore, we innovatively propose that Cd and Pb may have interactive effects on GCs levels, and Pb can antagonize the negative relationship between Cd and GCs, which may provide clues for further studies on endocrine and metabolic disorders related to these heavy metals.

Mixed heavy metals exposure affects the renal function mediated by 8-OHG: A cross-sectional study in rural residents of China.

Heavy metals are important risk factors for kidney, but their co-exposure effect on kidney and related mechanism remain unclear. This study evaluated the relationship between heavy metals and renal function, and the feasible mediation effect of oxidative stress. Based on the Dongdagou-Xinglong cohort, participants were recruited and their information were collected through questionnaires and physical examinations. The urine concentration of heavy metals like Cobalt, Nickel, Molybdenum, Cadmium, Antimony, Copper, Zinc, Mercury, Lead, Manganese, and renal injury biomarkers like ß2-microglobulin, ß-N-Acetylglucosaminidase, retinol-binding protein, 8-hydroxyguanine (8-OHG) were measured and corrected by creatinine. Linear regression was conducted to analyze the relationship between metals and renal biomarkers. Bayesian kernel machine regression, weighted quantile sum and quantile-based g-computation were applied to analyze the association between metal mixtures and renal biomarkers. Finally, the mediating effect of 8-OHG was analyzed through the mediation model. We found that these metals were positively related with renal biomarkers, where copper showed the strongest relationship. The co-exposure models showed that renal biomarkers increased with the concentration of mixtures, particularly for cadmium, copper, mercury, manganese. In addition, the proportion of 8-OHG in mediating effect of metals on renal function ranged from 2.6% to 86.9%. Accordingly, the renal function damage is positively associated with metals, and 8-OHG may play an important mediating role.

The Effect of Smoking Habits on Blood Cadmium and Lead Levels in Residents Living Near a Mining and Smelting Area in Northwest China: a Cross-Sectional Study.

Few studies have focused on environmental cadmium (Cd) and lead (Pb) exposure while exploring the effect of smoking on blood Cd (BCd) and blood Pb (BPb) levels. Moreover, essential trace elements affect the absorption, accumulation, and toxicity of Cd and Pb. To investigate the effect of smoking on BCd and BPb levels under high Cd and Pb exposure and the influence of essential trace elements on the effect, 301 residents living near a mining and smelting area in Northwest China were included in our study. After collecting health information and measuring BCd, BPb, serum iron, magnesium, and total calcium levels, we analyzed the association between smoking and BCd and BPb levels and the influence of the essential trace elements on the association. The results showed that BCd and BPb levels in smokers were significantly higher than those in non-smokers. There was a dose-response association between pack-years and the odds ratios (ORs) of high BCd and BPb levels in all participants compared with non-smokers. Serum iron, magnesium, and calcium had a negative effect on the elevations of the ORs of high BCd and BPb levels. In addition, smoking-related elevations of BCd and BPb levels vary by sex, age, BMI, and age of smoking initiation. Our findings present evidence for the effect of smoking on BCd and BPb levels under high Cd and Pb exposure and may provide guidance for the prevention and control of BCd and BPb elevations in residents living in Cd- and Pb-polluted areas.

Association among Helicobacter pylori Infection, Tooth Loss, and Heavy Medal Exposure in a Chinese Rural Population.

Previous research suggests that heavy metals may be associated with increased susceptibility to Helicobacter pylori infection. This study investigated the effect of heavy metal exposure (Pb and Cd) on tooth loss and H. pylori infection in a Chinese rural population, who live near a mining and smelting area. Blood samples were collected from the study participants to estimate the lead (Pb) and cadmium (Cd) exposure levels. H. pylori infection was analyzed using the 14C-urea breath test, and the number of missing teeth (MT), filled teeth (FT), and missing or filled teeth (MFT) were counted by conducting a physical examination. Regression analysis was used to assess the difference between H. pylori-positive and -negative individuals in the MT, FT, and MFT groups, adjusting for confounders. The H. pylori infection prevalence was higher in individuals in the high Cd or high Pb groups than that in the low Cd or low Pb groups (p < 0.05). In addition, greater numbers of FT and MFT were observed in individuals in the high Pb group than those in the low Pb group (p < 0.05). We further found 8.7% (95% CI, 2.8−23.8%, p = 0.017) of the effect of the high BPb level on H. pylori infection risk could be statistically explained by FT using amediation analyses in adjusted models, and 6.8% (95% CI, 1.6−24.8%, p = 0.066) by MFT. Furthermore, FT and MFT were significantly associated with increased risk for H. pylori infection (odds ratio (OR) = 4.938, 95% confidence interval (CI): 1.125−21.671; OR = 3.602, 95% CI: 1.218−10.648, respectively). Pb and Cd exposure may be associated with tooth loss and increased susceptibility to H. pylori infection, and tooth loss may be an independent risk factor for H. pylori infection.

Physical activity reduces the role of blood cadmium on depression: A cross-sectional analysis with NHANES data.

Cadmium (Cd) exposure is recognized as an important risk factor for psychological health, but suitable physical activity may relieve depression. However, it remains unknown whether physical activity (PA) can reduce the effect of cadmium exposure on depression. Therefore, a cross-sectional data from National Health and Nutrition Examination Survey (NHANES) 2015-2018 was used. The Nine-item Patient Health Questionnaire (PHQ-9) was used to assess depression among the participants. PA was calculated according to the metabolic equivalent (MET), weekly frequency, and duration of each activity. Logistic regression and restricted cubic spline models were used to examine the associations of Cd and depression. A total of 5560 adults aged 20 years and above were finally included in this study. The results indicated a positive correlation between blood Cd and depression. The multivariate-adjusted ORs (95% CI) of the highest quartile were 2.290 (1.754-2.990) for depression, which was still significant after controlling other heavy metals (P < 0.05). Under Cd exposure, the high intensity of physical activity group had the lowest risk of depression (OR = 2.226, 95%CI: 1.447-3.425), while the group with no physical activity had the highest risk (OR = 2.443, 95%CI: 1.382-4.318). Our results indicate that inner Cd exposure may be a risk factor for depression, and physical activity can moderate this relationship to some degree.

Ambient temperature, humidity, and urinary system diseases: a population-based study in Western China.

Climate has received an increasing attention due to its adverse effects on human health, but the effects on the urinary system are still short of enough evidence. Therefore, we carry out this study to analyze the relationship between meteorological factors and urinary system health in arid areas of western China. In this study, the daily numbers of outpatients with the urinary system diseases from multiple hospitals in three cities in Gansu province (Lanzhou, Zhangye, and Tianshui city) were collected and used for analysis. The distributed lag non-linear models (DLNM) with a quasi-Poisson distribution were used to estimate the associations between meteorological factors and daily outpatients for urinary system diseases in these three cities, and then a multivariate meta-analysis was applied to pool the estimates of city-specific effects. We found that the ambient temperature (AT) and relative humidity (RH) were significantly associated with the outpatient visits of urinary system diseases. The effects of meteorological factors on outpatients with urinary system diseases for both males and females were statistically significant at different lag days. The higher AT and lower RH were associated with the higher risk of urinary system diseases. We also observed substantial lag effects of meteorological factors on outpatients for both males and females. Among all disease types, renal tubule-interstitial diseases had the strongest relationships with meteorological factors. Our results indicate that the higher AT and lower RH may increase the outpatient visits for urinary system diseases, with significant lag effects in semi-arid areas.

Effects of lead and cadmium co-exposure on liver function in residents near a mining and smelting area in northwestern China.

Chronic exposure to environmental cadmium (Cd) and lead (Pb) may have adverse effects on the human health. In this study, we aimed to determine the primary and interactive effects of Cd and Pb exposure on liver function in residents near a mining and smelting area in northwestern China. A total of 451 subjects were recruited, from which blood samples were collected to determine the levels of Cd, Pb, and liver function indices. Additionally, the association between the levels of exposure markers and liver function indices was analysed. Cd and Pb levels were significantly higher in subjects living in the polluted area than in those living in the non-polluted reference area. The liver function levels of subjects in the polluted area were poor compared with those in the reference area. In addition, Cd and Pb levels in the blood were positively associated with gamma glutamyl transpeptidase (GGT) levels and negatively associated with direct bilirubin (DBil) levels. Cd and Pb may be risk factors for abnormal liver function. The risk of abnormal liver function was higher in subjects with moderate Cd and Pb levels, high Cd levels, high Pb levels, and high Cd and Pb levels than in those with low Cd and Pb levels. Our data show that exposure to Cd and/or Pb can cause abnormal liver function. Cd and Pb may have an antagonistic effect on liver function, and high Cd exposure alone has a more profound effect on abnormal liver function compared with co-exposure to Pb and Cd.

The Effects of Lead and Cadmium Co-exposure on Serum Ions in Residents Living Near a Mining and Smelting Area in Northwest China.

In this study, we investigated the associations between cadmium (Cd) and lead (Pb) co-exposure, and serum ion levels in two populations living near a mining/smelting area and a nature reserve (control area), respectively. A total of 445 participants were included in this study. Their blood cadmium (BCd), blood lead (BPb), and serum ion levels were determined, and the association between exposure levels and serum ion levels was analyzed. The exposure levels of subjects living in the polluted area were significantly higher (p < 0.001). Lower levels of potassium, inorganic phosphorus, and iron were observed in subjects from the polluted area, whereas their sodium and chloride levels were higher (p < 0.01). The anion gap in their serum was also significantly lower. We observed positive dose-effect relationships between Cd and/or Pb exposure and serum sodium and chloride, and negative dose-effect relationships between Cd and/or Pb exposure and serum inorganic phosphorus, iron, as well as the anion gap. High Cd-Pb, high Cd, and high Pb exposure led to modification effects in potassium, calcium, inorganic phosphorus, and iron levels, and the anion gap. No synergistic effects were observed in our results. In conclusion, our data demonstrate that Cd and Pb exposure, alone or in combination, can lead to serum ion imbalances.

Association between lead and cadmium co-exposure and systemic immune inflammation in residents living near a mining and smelting area in NW China.

Exposure to both cadmium (Cd) and lead (Pb) can promote systemic inflammation. However, the effects of combined exposure to environmental levels of Cd and Pb on systemic immune inflammation have not been fully clarified. A total of 486 subjects (313 women and 173 men) living in either a control area or heavy metal-polluted area were included. Blood Cd and Pb and immune inflammation biomarkers were determined, including the eosinophil-lymphocyte ratio (ELR), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and systemic immune-inflammation index (SII); moreover, the associations between exposure markers and systemic inflammation markers were analysed. The exposure levels in the polluted area were significantly higher than those in the control area. The NLR, PLR, and SII of subjects in the polluted area were higher and the LMR was lower than in the control area. Blood Pb and Cd levels are associated with elevated or decreased immune inflammation biomarkers in subjects from the exposed and control areas. Furthermore, co-exposure to both Cd and Pb was divided into high, middle, and low exposure groups. The subjects in the high co-exposure group displayed higher levels of ELR, NLR, and SII compared with the middle and low co-exposure group, and LMR levels displayed the opposite trend. Our data demonstrate that Cd and Pb co-exposure is associated with systemic immune inflammation, and the immune inflammatory response is aggravated with an increased co-exposure to Cd and Pb.

Airborne particulate matter (PM2.5) triggers ocular hypertension and glaucoma through pyroptosis.

BACKGROUND: Particulate matter (PM) is strongly linked to human health and has detrimental effects on the eye. Studies have, however, focused on the ocular surface, with limited research on the impact of PM2.5 on intraocular pressure (IOP). METHODS: To investigate the impact of PM2.5 on IOP and the associated mechanism, C57BL/6 mouse eyes were topically exposed to a PM2.5 suspension for 3 months, and human trabecular meshwork (HTM) cells were subjected to various PM2.5 concentrations in vitro. Cell viability, NLRP3/caspase-1, IL-1ß, and GSDMD expression, reactive oxygen species (ROS) production and cell contractility were measured by western blot, ELISA, cell counting kit-8, ROS assay kit or a cell contractility assay. ROS scavenger N-acetyl-L-cysteine (NAC) and caspase-1 inhibitor VX-765 were used to intervene in PM2.5-induced damages. RESULTS: The results revealed that the IOP increased gradually after PM2.5 exposure, and upregulations of the NLRP3 inflammasome, caspase-1, IL-1ß, and GSDMD protein levels were observed in outflow tissues. PM2.5 exposure decreased HTM cell viability and affected contraction. Furthermore, elevated ROS levels were observed as well as an activation of the NLRP3 inflammasome and downstream inflammatory factors caspase-1 and IL-1ß. NAC improved HTM cell viability, inhibited the activation of the NLRP3 inflammasome axis, and HTM cell contraction by scavenging ROS. VX-765 showed similar protection against the PM2.5 induced adverse effects. CONCLUSION: This study provides novel evidence that PM2.5 has a direct toxic effect on intraocular tissues and may contribute to the initiation and development of ocular hypertension and glaucoma. This occurs as a result of increased oxidative stress and the subsequent induction of NLRP3 inflammasome mediated pyroptosis in trabecular meshwork cells.

Airborne particulate matter (PM2.5) triggers cornea inflammation and pyroptosis via NLRP3 activation.

Although studies have demonstrated that fine particulate matter (PM2.5) induces ocular surface damage, PM2.5 exposure causes cornea toxicity is not entirely clear. The aim of this study is to investigate the role of the nod-like receptor family pyrin domain containing three (NLRP3) inflammasome-mediated pyroptosis in PM2.5-related corneal toxicity. Human corneal epithelial cells (HCECs) were exposed to different concentrations of PM2.5, and the cell viability, expressions of NLRP3 inflammasome mediated pyroptosis axis molecules and intracellular reactive oxygen species (ROS) formation were measured in HCECs. Animal experiments were undertaken to topically apply PM2.5 suspension to mouse eyes for three months and the pyroptosis related molecules in the mouse corneas were measured. RESULTS: Our results showed a dose-dependent decrease of HCEC viability in the PM2.5-treated cells. NLRP3 inflammasome-mediated pyroptosis axis (NLRP3, ASC, GSDMD, caspase-1, IL-1ß, and IL-18) were activated in the PM2.5-treated HCECs, accompanied by increased ROS formation. Further in vivo study confirmed the activation of this pathway in the mouse corneas exposed to PM2.5. In conclusion, this study provids novel evidence that PM2.5 induces corneal toxicity by triggering cell pyroptosis.

Meteorological factors, governmental responses and COVID-19: Evidence from four European countries.

With the global lockdown, meteorological factors are highly discussed for COVID-19 transmission. In this study, national-specific and region-specific data sets from Germany, Italy, Spain and the United Kingdom were used to explore the effect of temperature, absolute humidity and diurnal temperature range (DTR) on COVID-19 transmission. From February 1st to November 1st, a 7-day COVID-19 case doubling time (Td), meteorological factors with cumulative 14-day-lagged, government response index and other factors were fitted in the distributed lag nonlinear models. The overall relative risk (RR) of the 10th and the 25th percentiles temperature compared to the median were 0.0074 (95% CI: 0.0023, 0.0237) and 0.1220 (95% CI: 0.0667, 0.2232), respectively. The pooled RR of lower (10th, 25th) and extremely high (90th) absolute humidity were 0.3266 (95% CI: 0.1379, 0.7734), 0.6018 (95% CI: 0.4693, 0.7718) and 0.3438 (95% CI: 0.2254, 0.5242), respectively. While the DTR did not have a significant effect on Td. The total cumulative effect of temperature (10th) and absolute humidity (10th, 90th) on Td increased with the change of lag days. Similarly, a decline in temperature and absolute humidity at cumulative 14-day-lagged corresponded to the lower RR on Td in pooled region-specific effects. In summary, the government responses are important factors in alleviating the spread of COVID-19. After controlling that, our results indicate that both the cold and the dry environment also likely facilitate the COVID-19 transmission.