Co-exposure to fluoride and sulfur dioxide induces abnormal enamel mineralization in rats via the FGF9-mediated MAPK signaling pathway.

Fluoride (F) and sulfur dioxide (SO2) contamination is recognized as a public health concern worldwide. Our previous research has shown that Co-exposure to F and SO2 can cause abnormal enamel mineralization. Ameloblastin (AMBN) plays a crucial role in the process of enamel mineralization. However, the process by which simultaneous exposure to F and SO2 influences enamel formation by regulating AMBN expression still needs to be understood. This study aimed to establish in vivo and in vitro models of F-SO2 Co-exposure and investigate the relationship between AMBN and abnormal enamel mineralization. By overexpressing/knocking out the Fibroblast Growth Factor 9 (FGF9) gene, we investigated the impact of FGF9-mediated Mitogen-Activated Protein Kinase (MAPK) signaling on AMBN synthesis to elucidate the mechanism underlying the induction of abnormal enamel mineralization by F-SO2 Co-exposure in rats. The results showed that F-SO2 exposure damaged the structure of rat enamel and ameloblasts. When exposed to F or SO2, gradual increases in the protein expression of FGF9 and phosphorylated p38 mitogen-activated protein kinase (p-P38) were observed. Conversely, the protein levels of AMBN, phosphorylated extracellular signal-regulated kinase (p-ERK), and phosphorylated c-Jun N-terminal kinase (p-JNK) were decreased. AMBN expression was significantly correlated with FGF9, p-ERK, and p-JNK expression in ameloblasts. Interestingly, FGF9 overexpression reduced the levels of p-ERK and p-JNK, worsening the inhibitory effect of F-SO2 on AMBN. Conversely, FGF9 knockout increased the phosphorylation of ERK and JNK, partially reversing the F-SO2-induced downregulation of AMBN. Taken together, these findings strongly demonstrate that FGF9 plays a critical role in F-SO2-induced abnormal enamel mineralization by regulating AMBN synthesis through the JNK and ERK pathways.

The role of FGF9-mediated TGF-ß1/Smad signaling in enamel hypoplasia induced by exposure to fluoride and SO2 in rats.

Many geographical areas of the world are polluted by both fluoride and sulfur dioxide (SO2). However, the effects of simultaneous exposure to fluoride and SO2 on teeth are unknown. Fibroblast growth factor-9 (FGF9) and transforming growth factor-ß1 (TGF-ß1) are key signaling molecules in enamel development. The purpose of the study was to explore the effects of co-exposure to fluoride and sulfur dioxide on enamel and to investigate the role and mechanism of FGF9 and TGF-ß1. First, sodium fluoride (NaF) and SO2 derivatives were used to construct rat models and evaluate the enamel development of rats. Then, TGF-ß1 (cytokine) treatment, SIS3 (inhibitor) treatment and FGF9 gene knockdown were used to explore the mechanism of enamel damage in vitro. The results showed that enamel column crystals in the exposed group were characterized by enamel hypoplasia, as indicated by alterations such as disarrangement of enamel column crystals, space widening and breakage. Ameloblasts also showed pathological changes such as ribosome loss, mitochondrial swelling, nuclear fragmentation and chromatin aggregation. The protein expression of FGF9 was higher and the protein expression of AMBN, TGF-ß1 and p-Smad2/3 protein was lower in the groups treated with fluoride and SO2 individually or in combination compared with the control group. Further studies showed that TGF-ß1 significantly upregulated p-Smad2/3 and AMBN protein expression and reduced the inhibitory effects of fluoride and SO2; furthermore, SISI blocked the effect of TGF-ß1. In addition, knockdown of FGF9 upregulated TGF-ß1 protein expression, further activated Smad2/3 phosphorylation, eliminated the inhibitory effects of fluoride and SO2, and increased the protein expression of AMBN. In brief, the study confirms that co-exposure to fluoride and SO2 can result in enamel hypoplasia in rats and indicates that the underlying mechanism may be closely related to the effect of FGF9 on enamel matrix protein secretion through inhibition of the TGF-ß1/Smad signaling pathway.

Analysis of multiple pathways and levels of fluoride intake in fluorosis areas of Southwest China.

In the coal-burning fluorosis areas of China, over 10 million people suffer from dental fluorosis caused by multiple pathways of fluoride intake. However, the link between dental fluorosis prevalence, the geochemical distribution of fluoride, and contributions of different exposure pathways remain unclear. Here, we aimed to quantify the various fluoride exposure pathways and establish the association between dental fluorosis and fluoride intake in Southwest China. Epidemiological data on the peak time of fluorosis prevalence were combined with geochemical analyses of the fluoride content in coal and clay over a large scale, the amounts and ratios of fluoride intake through different exposure pathways were calculated, and the association between the total daily fluoride intake (TDFI) and dental fluorosis severity was analyzed. The prevalence of dental fluorosis was not significantly correlated with the fluoride geo-background of coal and clay on a large scale (P > 0.05). The co-combustion of coal and clay contained in hand-made briquettes is the main pathway of fluoride contamination, which occurs through the inhalation of polluted air and consumption of contaminated roasted products. Furthermore, the TDFI per person ranged from 2.78 to 17.32 mg, and it was significantly positively correlated with the prevalence of dental fluorosis (P < 0.05). The TDFI from breathing and eating was 1.1-3.2 mg and 1.1-15.1 mg, which accounted for 9%-54% and 40%-90% of the total TDFI, respectively. The combination of living habits and soil geochemical fluoride anomalies resulted in the higher prevalence of fluorosis in rural areas of Southwest China.

Sulphur dioxide and fluoride co-exposure cause enamel damage by disrupting the Cl-/HCO3- ion transport.

OBJECTIVE: Although there is growing evidence linking the exposure to sulphur dioxide (SO2) and fluoride to human diseases, there is little data on the co-exposure of SO2 and fluoride. Moreover, literature on SO2 and fluoride co-exposure to enamel damage is insufficient. In this work, we concentrate on the concurrent environmental issues of excessive SO2 and fluoride in several coal-consuming regions. METHOD: To identify the toxicity of SO2 and fluoride exposure either separately or together, we used both ICR mice and LS8 cells, and factorial design was employed to assess the type of potential combined action. RESULT: In this study, co-exposure to SO2 and fluoride exacerbated enamel damage, resulting in more severe enamel defects of incisor and the damage occurred earlier. Cl-/HCO3- exchanger expression is increased by SO2 and fluoride in mouse incisor. Consistent with in vivo results, co-exposure of SO2 and fluoride decreased pHi and increased [Cl-]i level by increasing the expression of the Cl-/HCO3- exchanger in LS8 cells. Furthermore, SO2 and F may increase merlin protein expression, and merlin deficiency causes AE2 expression to decrease in vitro. CONCLUSION: Overall, these results indicate that co-exposure to SO2 and fluoride may result in more toxicity both in vitro and in vivo than a single exposure to SO2 and fluoride, suggesting that residents in areas contaminated with SO2 and fluoride may be more likely to suffer enamel damage.

Determination of cadmium in Chinese pepper and its health implications based on bioaccessibility.

The contamination of cadmium (Cd) in agro-products causes major concern because of its potential dietary risks. In this study, a total of 647 pepper samples from 21 provinces in China were randomly collected according to the distribution of pepper production. Cd pollution levels in Chinses pepper and its health risks were evaluated based on bioaccessibility, which was measured by the physiologically based extraction test (PBET). The results showed that Cd concentration in all pepper ranged from 0.002 to 1.470 mg/kg, with an average of 0.222 mg/kg and a median of 0.132 mg/kg. The highest daily intake of Cd was observed in the female child group (4.037 × 10-5 mg/kg bw/day), which accounted for 4% of the maximum daily permissible dose - 0.001 mg/kg bw/day. The target hazard quotients of Cd were all lower than 1, indicating low potential non-carcinogenic health risks to residents via the consumption of pepper. Notably, carcinogenic risk values suggested potential adverse health effects to adults, while after considering the bioaccessibility of Cd in pepper (mean of 43.07%), those values had fallen under the acceptable level (1 × 10-4). This may indicate that dietary risk assessment of heavy metals in crops could not be conducted just based on their content; the bioaccessibility of metals is also an important factor for consideration.

Sodium Fluoride and Sulfur Dioxide Derivatives Induce TGF-ß1-Mediated NBCe1 Downregulation Causing Acid-Base Disorder of LS8 Cells.

The aim of the present work was to assess whether the combination of sodium fluoride (NaF) and sulfur dioxide derivatives (SO2 derivatives) affects the expression of the electrogenic sodium bicarbonate cotransporter NBCe1 (SLC4A4), triggering an acid-base imbalance during enamel development, leading to enamel damage. LS8 cells was taken as the research objects and fluorescent probes, quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and factorial analysis were used to clarify the nature of the fluoro-sulfur interaction and the potential signaling pathway involved in the regulation of NBCe1. The results showed that exposure to fluoride or SO2 derivatives resulted in an acid-base imbalance, and these changes were accompanied by inhibited expression of NBCe1 and TGF-ß1; these effects were more significant after fluoride exposure as compared to exposure to SO2 derivatives. Interestingly, in most cases, the toxic effects during combined exposure were significantly reduced compared to the effects observed with fluoride or sulfur dioxide derivatives alone. The results also indicated that activation of TGF-ß1 signaling significantly upregulated the expression of NBCe1, and this effect was suppressed after the Smad, ERK, and JNK signals were blocked. Furthermore, fluoride and SO2 derivative-dependent NBCe1 regulation was found to require TGF-ß1. In conclusion, this study indicates that the combined effect of fluorine and sulfur on LS8 cells is mainly antagonistic. TGF-ß1 may regulate NBCe1 and may participate in the occurrence of dental fluorosis through the classic TGF-ß1/Smad pathway and the unconventional ERK and JNK pathways.

Sulphur dioxide and fluoride co-exposure induce incisor hypomineralization and amelogenin upregulation via YAP/RUNX2 signaling pathway.

Sulphur dioxide (SO2) and fluoride are among the most common environmental pollutants affecting human health, and both co-exist in areas predominantly consuming coal. It is vital to analyse the combined toxicity of SO2 and fluoride, and their effects on health and the underlying mechanisms of their co-exposure have not yet been adequately assessed. In the present study, we used ICR mice and LS8 cells to investigate the toxicity of SO2 and fluoride exposure to the enamel, alone or in combination. Factorial design analysis was used to reveal the combined toxicity in vitro and in vivo. Co-exposure to SO2 and fluoride exacerbated enamel injury, resulting in more severe hypomineralization of incisor, and enamel structure disorders in mice, and could induce the accumulation of protein residue in the matrix of the enamel. Amelogenin expression was increased upon exposure to SO2 and fluoride, but enamel matrix proteases were not affected. Consistent with our in vivo results, co-exposure of SO2 and fluoride aggravated amelogenin expression in LS8 cells, and increased the YAP and RUNX2 levels. Co-exposure to SO2 and fluoride resulted in greater toxicity than individual exposure, both in vitro and in vivo, indicating that residents of areas exposed to SO2 and fluoride may have an increased risk of developing enamel damage.

[Spatial Variation and Influencing Factors of Soil pH in Anshun City].

Exploring the spatial distribution characteristics and variation law of soil pH and analyzing the impact of environmental factors on the spatial differentiation of soil pH are of great significance to the accurate management of soil pH and the sustainable utilization of soil resources in the complex mountainous environment of Anshun City. Based on 22 851 field sampling points, using the methods of global Moran's I index, cold and hot spot analysis, semi-variance function, and Kriging interpolation, the spatial structure characteristics and distribution law of soil pH in Anshun City were revealed from different angles, and the influence of environmental factors on its spatial differentiation was analyzed with the help of geographic detectors. The results showed that:① the variation range of topsoil pH value in Anshun City was 3.56-8.61, the mean value was 6.28, and the coefficient of variation was 16.33%. ② In the global space, soil pH showed aggregation distribution; in the local space, the west and northwest were hot spots, whereas the east and south were cold spots. The nugget coefficient (40.19%) showed that the spatial variability in soil pH was determined by both structural and random factors, but the role of structural factors was greater. ③ In terms of spatial distribution, soil pH mainly presented a patchy mosaic distribution pattern, in which slightly acidic soil (57.14%) was concentrated in the east, northeast, and south of Anshun City; neutral soil (30.13%) was concentrated in the west, northwest, and southeast; and strongly acidic soil (6.12%) and alkaline soil (6.45%) were embedded in slightly acidic soil and neutral soil, respectively, in a block structure. ④ The geo-detector analysis showed that the explanatory power of various environmental factors to the spatial variation in soil pH was ranked as soil type (9.4%)>soil forming parent rock (7.9%)>altitude (2.1%)>land use (1.8%)>slope (0.1%), in which the q value of the interaction between soil type and parent rock type and other factors was large. Therefore, soil type and parent rock type were the main controlling factors of soil pH spatial variation in Anshun City.

An Improved Bibliometric Analysis on Antibiotics in Soil Research.

Antibiotic compounds can enter the environment and eventually into drinking water, when manure containing non-metabolized antibiotic residues is applied to agricultural land. In this study, the publication data was analyzed from the aspects of countries, subject categories and keywords during the period of 1946-2016 from Web of Science. The results indicated that, during the period of 2004-2016, the United States, followed by China, dominated the publication of antibiotics in soil. Three most representative subject categories were "Microbiology", "Environmental science and ecology" and "Chemistry". The most studied antibiotic was tetracycline. Antibiotic resistance bacteria (ARB) and antibiotic resistance genes (ARGs) with the fate and transport mechanisms such as degradation, adsorption and desorption were the hot research topics in this field. This study suggests that research on ARB, ARGs and antibiotics in soil should be paid more attention in the future research.

Fluorine enrichment of vegetables and soil around an abandoned aluminium plant and its risk to human health.

In the process of electrolytic aluminium production, a large amount of fluoride is deposited into the surrounding environment. The growth of crops within these areas creates a state of high stress in plants that can easily result in excessive fluorine enrichment in agricultural products, which in turn poses a health threat to humans via the food chain. However, it is not clear what the degree of influence is or how long the impacts of fluorides in soil and agricultural products last for. In this study, 122 vegetable species and 36 surface soil samples were collected within 10 km of an aluminium plant that had been abandoned for five years. The single factor index and the geological accumulation index methods were used to evaluate the degree of fluorine pollution in vegetables and soil within the study area. The hazard index and the hazard quotient were used to assess vegetable and soil health risks, respectively. The results showed that the fluorine content of 89.26% of agricultural products exceeded the Chinese Maximum Levels of Contaminants in Foods and was higher than in other regions, indicating that the emissions of fluoride from the aluminium plant still had a significant effect on fluorine accumulation in vegetables. The total fluorine (Ft) content in the surrounding surface soil (average value 1328.32 mg kg-1) was similar to the soil fluorine background in the nearby uncontaminated settlement area, but the soil water-soluble fluorine (Fw) was very high, indicating that the fluorine pollutants emitted from the aluminium plant had gradually been diluted by the high background of the original soil, but the solubility of these pollutants was higher (average 15.00 mg kg-1) and would continue to threaten the safety of agricultural products in this region. Within 1 km of the abandoned aluminium plant, the degree of fluorine enrichment in vegetables, and Ft and Fw in soil were significantly higher than other ranges, indicating that this was the main fluoride deposit area. Based on the HI and HQ evaluation, vegetables and ground dust around the aluminium plant still had high non-carcinogenic risks for children, even though it has been abandoned for more than five years.

Relationships between soil properties and the accumulation of heavy metals in different Brassica campestris L. growth stages in a Karst mountainous area.

The speciation and activity of heavy metals in farmland were changed with the different soil properties and flooded environment, especially in the complex and rainy environment in soil of Guizhou Province. The objective of this study was to explore the concentrations of a variety of heavy metal activity and the speciation of those heavy metals in rhizosphere soil at different growth stages of Brassica campestris L. in a Karst mountainous area. Tessier's five-stage sequential extraction procedure, the potential ecological risk index, a Bayesian network, accumulation factors, translocation factors and a laboratory simulation experiment were applied in this study. The results showed that (1) no heavy metal concentrations (except the Cd concentration) exceeded the limits of the soil environmental quality risk control standards for soil contamination of agricultural land in China (GB15618-2018). (2) The orders of the accumulation factor and translocation factor values were Zn > Cd > Cu > Pb > Cr and Cd > Cu > Zn > Pb > Cr, respectively. The order of the heavy metal contents of different tissues during the whole growth period was roots > leaves > stems. (3) The indoor simulation test exhibited that the dry-wet alternation and flooding can reduce Cd activity in soil. (4) Redox potential (Eh), rather than pH or organic matter, was the main factor impacting the total content and chemical speciation of heavy metals in the soil, based on a dynamic Bayesian network. Based on the results, we suggest that the activity of heavy metals should be improved by using dry-wet alternation, whereas the proportions of ion-exchangeable forms of heavy metals are relatively low in the study area (except for Cd). Several measures may be taken to enhance soil acidity and reduce the Cd activity during Brassica campestris L. cultivation.

Effects of land use and parent materials on trace elements accumulation in topsoil.

To determine the effects of parent material and land use on the concentration of trace elements in the agricultural topsoil of Guizhou Province, China, a total of 584 agricultural topsoil samples were collected in a typical region. The results indicate that the contents of trace elements (As, Cd, Cr, Hg, and Pb) in agricultural soils were greater than in the uncultivated soils, and the paddy fields exhibited higher contents of trace elements than dry lands. The enrichments of most trace elements in agricultural topsoil derived from carbonate rock were more serious. In paddy fields, Cd, Cr, and As showed positive relationships with soil organic matter ( < 0.01) but were not affected by pH, carbon-to-nitrogen (C/N) ratio, and clay ( > 0.05). Lead and Hg formed the second component in principal component analysis (PCA) and were closely related to pH and clay content. In dry lands, the trace elements were well correlated with pH, C/N, and clay ( < 0.05). Analysis of PCA and correlation showed that Cd, Cr, and Hg were mainly derived from inorganic fertilizers, whereas Pb and As were primarily from organic manures. These results suggest that the effect of anthropogenic activities on paddy fields is more serious than on dry lands. Parent materials not only serve as sources of soil trace elements but also control the loss and accumulation of trace elements by affecting soil physicochemical properties, especially in dry lands.

[Soil organic carbon variation of de-farming and wasteland during alteration of ecosystem in Billabong].

Four soil profile samples were collected in the middle of de-farming and wasteland billabong and around slopes, located at typical karst district of Guizhou province. Soil organic matter (SOC) content and delta Corg, were determined. SOC content ranged from 6.0 mg x kg(-1) to 92.3 mg x kg(-1), and decreased with depth at slope soil profiles. The range of value was bigger than that at billabong soil profile (6.3-26.7 mg x kg(-1)). The value of detla13 Corg, at slope profiles was between - 25.103% per hundred and - 23.666% per hundred, but variation direction of three slope soil profiles was different. The value of delta 13Corg, in billabong soil profile was between - 23.495% per hundred and - 20.809% per hundred, and increased with depth. The correlation between delta13 Csoc and C4-C,C3-C was significant (R = 0.884, n=7), influenced by new C3-C.