Effect of arsenic on the risk of gestational diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: Gestational diabetes mellitus (GDM) is a complication of pregnancy associated with numerous adverse outcomes. There may be a potential link between GDM and arsenic (As) exposure, but this hypothesis remains controversial. This meta-analysis summarizes the latest studies evaluating the association between As and GDM. METHODS: A comprehensive search of the PubMed, Embase, and Scopus databases up to September 2023 was performed. The pooled estimates with 95% CIs were presented using forest plots. Estimates were calculated with random effects models, and subgroup and sensitivity analyses were conducted to address heterogeneity. RESULTS: A total of 13 eligible studies involving 2575 patients with GDM were included in this meta-analysis. The results showed that women exposed to As had a significantly increased risk of GDM (OR 1.47, 95% CI: 1.11 to 1.95, P = 0.007). Subgroup analyses suggested that the heterogeneity might be attributed to the years of publication. In addition, sensitivity analysis confirmed the robust and reliable results. CONCLUSIONS: This analysis suggested that women exposed to As have a greater risk of GDM. However, the significant heterogeneity across studies requires careful interpretation. REGISTRATION: The PROSPERO registration ID is CRD42023461820.

Transgenerational Effects of Arsenic Exposure on Learning and Memory in Rats: Crosstalk between Arsenic Methylation, Hippocampal Metabolism, and Histone Modifications.

Arsenic (As) is widely present in the natural environment, and exposure to it can lead to learning and memory impairment. However, the underlying epigenetic mechanisms are still largely unclear. This study aimed to reveal the role of histone modifications in environmental levels of arsenic (sodium arsenite) exposure-induced learning and memory dysfunction in male rats, and the inter/transgenerational effects of paternal arsenic exposure were also investigated. It was found that arsenic exposure impaired the learning and memory ability of F0 rats and down-regulated the expression of cognition-related genes Bdnf, c-Fos, mGlur1, Nmdar1, and Gria2 in the hippocampus. We also observed that inorganic arsenite was methylated to DMA and histone modification-related metabolites were altered, contributing to the dysregulation of H3K4me1/2/3, H3K9me1/2/3, and H3K4ac in rat hippocampus after exposure. Therefore, it is suggested that arsenic methylation and hippocampal metabolism changes attenuated H3K4me1/2/3 and H3K4ac while enhancing H3K9me1/2/3, which repressed the key gene expressions, leading to cognitive impairment in rats exposed to arsenic. In addition, paternal arsenic exposure induced transgenerational effects of learning and memory disorder in F2 male rats through the regulation of H3K4me2 and H3K9me1/2/3, which inhibited c-Fos, mGlur1, and Nmdar1 expression. These results provide novel insights into the molecular mechanism of arsenic-induced neurotoxicity and highlight the risk of neurological deficits in offspring with paternal exposure to arsenic.

Arsenic aggravates the progression of diabetic nephropathy through miRNA-mRNA-autophagy axis.

Environmental factors play an important role in the progression of diabetic nephropathy (DN), and previous study has shown that arsenic exposure can promote kidney damage in DN rats, however there is no relevant mechanism study so far. In this study, an arsenic-exposed (10 mg/L and 25 mg/L) DN mouse model was established through drinking water for 14 weeks. The results showed that 25 mg/L arsenic exposure increased the renal fibrosis in DN mice significantly, and urinary mAlb level increased with the increasing of arsenic exposure level. Transcriptome sequencing showed that autophagy-related pathways were significantly activated under the exposure dose of 25 mg/L, and levels of Beclin1 and p-ATG16L1/ATG16L1 were significantly higher in the 25 mg/L arsenic group compared to the control group. Silico analysis predicted the microRNAs those could regulate the hub genes of Mapk1, Rhoa and Cdc42, and dual-luciferase gene reporter assay was used to verify the targeted binding between these mRNAs and microRNAs. Our results suggested that high arsenic exposure could aggravate the progression of DN by altering autophagy, the miRNA-mRNA axles of let-7a-1-3p, let-7b-3p, let-7f-1-3p, miR-98-3p/Cdc42, Mapk1, Rhoa, could be considered promising targets to explore the mechanisms and therapeutic measures of DN after exposure to high levels of arsenic.

Significance of dietary quinoa husk (Chenopodium quinoa) in gene regulation for stress mitigation in fish.

The persistent challenges posed by pollution and climate change are significant factors disrupting ecosystems, particularly aquatic environments. Numerous contaminants found in aquatic systems, such as ammonia and metal toxicity, play a crucial role in adversely affecting aquaculture production. Against this backdrop, fish feed was developed using quinoa husk (the byproduct of quinoa) as a substitute for fish meal. Six isonitrogenous diets (30%) and isocaloric diets were formulated by replacing fish meal with quinoa husk at varying percentages: 0% quinoa (control), 15, 20, 25, 30 and 35%. An experiment was conducted to explore the potential of quinoa husk in replacing fish meal and assess its ability to mitigate ammonia and arsenic toxicity as well as high-temperature stress in Pangasianodon hypophthalmus. The formulated feed was also examined for gene regulation related to antioxidative status, immunity, stress proteins, growth regulation, and stress markers. The gene regulation of sod, cat, and gpx in the liver was notably upregulated under concurrent exposure to ammonia, arsenic, and high-temperature (NH3 + As + T) stress. However, quinoa husk at 25% downregulated sod, cat, and gpx expression compared to the control group. Furthermore, genes associated with stress proteins HSP70 and DNA damage-inducible protein (DDIP) were significantly upregulated in response to stressors (NH3 + As + T), but quinoa husk at 25% considerably downregulated HSP70 and DDIP to mitigate the impact of stressors. Growth-responsive genes such as myostatin (MYST) and somatostatin (SMT) were remarkably downregulated, whereas growth hormone receptor (GHR1 and GHRß), insulin-like growth factors (IGF1X, IGF2X), and growth hormone gene were significantly upregulated with quinoa husk at 25%. The gene expression of apoptosis (Caspase 3a and Caspase 3b) and nitric oxide synthase (iNOS) were also noticeably downregulated with quinoa husk (25%) reared under stressful conditions. Immune-related gene expression, including immunoglobulin (Ig), toll-like receptor (TLR), tumor necrosis factor (TNFα), and interleukin (IL), strengthened fish immunity with quinoa husk feed. The results revealed that replacing 25% of fish meal with quinoa husk could improve the gene regulation of P. hypophthalmus involved in mitigating ammonia, arsenic, and high-temperature stress in fish.

Arsenic Exposure-Related Hypertension in Bangladesh and Reduced Circulating Nitric Oxide Bioavailability.

BACKGROUND: Hypertension is a major cause of death worldwide. Although arsenic exposure has been associated with the risk of hypertension, this association appears nonuniform due to inconsistent results from studies conducted in different populations. Moreover, hypertension is a complex condition with multiple underlying mechanisms and factors. One factor is impaired production and bioavailability of vascular nitric oxide (NO). However, the implications of the effects of arsenic exposure on circulating NO and its association with hypertension in humans are largely unknown. OBJECTIVE: We investigated the dose-response relationship between arsenic exposure and hypertension with vascular NO levels as a potential mediator of arsenic-related hypertension in individuals exposed to a broad range of arsenic. METHODS: A total of 828 participants were recruited from low- and high-arsenic exposure areas in Bangladesh. Participants' drinking water, hair, and nail arsenic concentrations were measured by inductively coupled plasma mass spectroscopy. Hypertension was defined as a systolic blood pressure (SBP) value of ≥140 and a diastolic (DBP) value of ≥90 mmHg. Serum NO levels reflected by total serum nitrite concentrations were measured by immunoassay. A formal causal mediation analysis was used to assess NO as a mediator of the association between arsenic level and hypertension. RESULTS: Increasing concentrations of arsenic measured in drinking water, hair, and nails were associated with the increasing levels of SBP and DBP. The odds of hypertension were dose-dependently increased by arsenic even in participants exposed to relatively low to moderate levels (10-50µg/L) of water arsenic [odds ratios (ORs) and 95% confidence intervals (CIs): 2.87 (95% CI: 1.28, 6.44), 2.67 (95% CI: 1.27, 5.60), and 5.04 (95% CI: 2.71, 9.35) for the 10-50µg/L, 50.01-150µg/L, and >150µg/L groups, respectively]. Causal mediation analysis showed a significant mediating effect of NO on arsenic-related SBP, DBP, and hypertension. CONCLUSION: Increasing exposure to arsenic was associated with increasing odds of hypertension. The association was mediated through the reduction of vascular NO bioavailability, suggesting that impaired NO bioavailability was a plausible underlying mechanism of arsenic-induced hypertension in this Bangladeshi population. https://doi.org/10.1289/EHP13018.

Transporters and phytohormones analysis reveals differential regulation of ryegrass (Lolium perenne L.) in response to cadmium and arsenic stresses.

Cadmium (Cd) and arsenic (As) are two highly toxic heavy metals and metalloids that coexist in many situations posing severe threats to plants. Our investigation was conducted to explore the different regulatory mechanisms of ryegrass (Lolium perenne L.) responding to individual and combined Cd and As stresses in hydroponics. Results showed that the ryegrass well-growth phenotype was not affected by Cd stress of 10 mg·L-1. However, As of 10 mg·L-1 caused rapid water loss, proline surge, and chlorosis in shoots, suggesting that ryegrass was highly sensitive to As. Transcriptomic analysis revealed that the transcription factor LpIRO2 mediated the upregulation of ZIP1 and YSL6 that played an important role in Cd tolerance. We found that the presence of As caused the overexpression of LpSWT12, a process potentially regulated by bHLH14, to mitigate hyperosmolarity. Indoleacetic acid (IAA) and abscisic acid (ABA) contents and expression of their signaling-related genes were significantly affected by As stress rather than Cd. We predict a regulatory network to illustrate the interaction between transporters, transcription factors, and signaling transduction, and explain the antagonism of Cd and As toxicity. This present work provides a research basis for plant protection from Cd and As pollution.

Arsenic stress on soil microbial nutrient metabolism interpreted by microbial utilization of dissolved organic carbon.

In a 120-day microcosm incubation experiment, we investigated the impact of arsenic contamination on soil microbial nutrient metabolism, focusing on carbon cycling processes. Our study encompassed soil basal respiration, key enzyme activities (particularly, ß-1,4-N-acetylglucosaminidase and phosphatases), microbial biomass, and community structure. Results revealed a substantial increase (1.21-2.81 times) in ß-1,4-N-acetylglucosaminidase activities under arsenic stress, accompanied by a significant decrease (9.86%-45.20%) in phosphatase activities (sum of acid and alkaline phosphatases). Enzymatic stoichiometry analysis demonstrated the mitigation of microbial C and P requirements in response to arsenic stress. The addition of C-sources alleviated microbial C requirements but exacerbated P requirements, with the interference amplitude increasing with the complexity of the C-source. Network analysis unveiled altered microbial nutrient requirements and an increased resistance process of microbes under arsenic stress. Microbial carbon use efficiency (CUE) and basal respiration significantly increased (1.17-1.59 and 1.18-3.56 times, respectively) under heavy arsenic stress (500 mg kg-1). Arsenic stress influenced the relative abundances of microbial taxa, with Gemmatimonadota increasing (5.5-50.5%) and Bacteroidota/ Nitrospirota decreasing (31.4-47.9% and 31.2-63.7%). Application of C-sources enhanced microbial resistance to arsenic, promoting cohesion among microorganisms. These findings deepen our understanding of microbial nutrient dynamics in arsenic-contaminated areas, which is crucial for developing enzyme-based toxicity assessment systems for soil arsenic contamination.

Toxic metals and pediatric clinical immune dysfunction: A systematic review of the epidemiological evidence.

BACKGROUND: Children are at high risk for exposure to toxic metals and are vulnerable to their effects. Significant research has been conducted evaluating the role of these metals on immune dysfunction, characterized by biologic and clinical outcomes. However, there are inconsistencies in these studies. The objective of the present review is to critically evaluate the existing literature on the association between toxic metals (lead, mercury, arsenic, and cadmium) and pediatric immune dysfunction. METHODS: Seven databases (PubMed (NLM), Embase (Elsevier), CINAHL (Ebsco), Web of Science (Clarivate Analytics), ProQuest Public Health Database, and ProQuest Environmental Science Collection) were searched following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in February 2024. Rayaan software identified duplicates and screened by title and abstract in a blinded and independent review process. The remaining full texts were reviewed for content and summarized. Exclusions during the title, abstract, and full-text reviews included: 1) not original research, 2) not epidemiology, 3) did not include toxic metals, 4) did not examine an immune health outcome, or 5) not pediatric (>18 years). This systematic review protocol followed the PRISMA guidelines. Rayaan was used to screen records using title and abstract by two blinded and independent reviewers. This process was repeated for full-text article screening selection. RESULTS: The search criteria produced 7906 search results; 2456 duplicate articles were removed across search engines. In the final review, 79 studies were included which evaluated the association between toxic metals and outcomes indicative of pediatric immune dysregulation. CONCLUSIONS: The existing literature suggests an association between toxic metals and pediatric immune dysregulation. Given the imminent threat of infectious diseases demonstrated by the recent COVID-19 epidemic in addition to increases in allergic disease, understanding how ubiquitous exposure to these metals in early life can impact immune response, infection risk, and vaccine response is imperative.

Toxicological profile and potential health concerns through metals and trace elements exposure in brick kiln workers from Lahore, Pakistan.

This study examined levels of lead (Pb), cadmium (Cd), chromium (Cr), copper (Cu), mercury (Hg), and arsenic (As) in blood, hair, and nails of 18 brick kiln workers from three brick kiln units located around a metropolitan city, Lahore, Pakistan. All the trace elements except Hg and As were detected in the studied matrices of Brick kiln workers. In general, brick kiln workers reflect the highest concentration of Pb, followed by Cd, Cr, and Cu. Of the pollutants analyzed, Pb has the highest mean (min-max) concentrations at 0.35 (0.09-0.65) in blood (µg/mL), 0.34 (0.14-0.71) in hairs (µg/g), and 0.44 (0.32-0.59) in nails (µg/g) of brick kiln workers. Following Pb, the trend was Cd 0.17 (0.10-0.24), Cu 0.11(0.03-0.27), and Cr 0.07 (0.04-0.08) in blood (µg/mL), followed by Cr 0.11(0.05-0.20), Cd 0.09 (0.03-0.13), and Cu 0.08 (0.04-0.16) in hairs (µg/g) and Cu 0.16 (0.05-0.36), Cd 0.13 (0.11-0.17), and Cr 0.10 (0.05-0.14) in nails (µg/g) respectively. Relatively higher concentrations of metals and other trace elements in blood depicts recent dietary exposure. The difference of trace elements except Pb was non-significant (P > 0.05) among studied matrices of workers as well as between Zigzag and traditional exhaust-based brick kilns. The concentrations of Pb, Cd and Cr in blood of brick kilns workers are higher than the values reported to cause health problems in human populations. It is concluded that chronic exposure to metals and other trace elements may pose some serious health risks to brick kiln workers which needs to be addressed immediately to avoid future worst-case scenarios.

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.

The probable reasons of arsenic susceptibility in a chronically exposed population of West Bengal.

Arsenic is potent human carcinogen which affects millions of people across the globe. Arsenic induced pre-cancerous and cancerous skin lesions are hall marks of chronic arsenic toxicity. Even then, only 15%-20% of the population manifest arsenic-induced skin lesions but the rest do not, the reason for which in not very clear. Not only that, conjunctival irritations of the eyes, peripheral neuropathy and respiratory distress are the non-dermatological health effects which are often manifested in them in addition to the cancers of skin and other internal organs. In this work we have considered 233 arsenic exposed individuals with skin lesions and 205 arsenic exposed individuals without skin lesions from the highly arsenic affected Murshidabad district of West Bengal. We have compared arsenic exposure in the two groups through drinking water. Both the study groups have similar levels of arsenic exposure, drinking same arsenic laden water. Results show that higher amounts of arsenic were retained in the nails and hair of the skin lesion group compared to the no skin lesion group. Significant higher amounts of chromosomal aberration and micronucleus formation were found in the skin lesion group, than the no skin lesion group. Incidences of conjunctival irritations of the eyes, peripheral neuropathy and respiratory distress were much higher in the former group compared to the later. We, thus found that one group was more susceptible than the other, even with similar levels of arsenic exposure. We have tried to identify and discuss the probable reasons for this observation with reference to our previous works in the exposed population from West Bengal, India.

Sustained effects of developmental exposure to inorganic arsenic on hepatic gsto2 expression and mating success in zebrafish.

The impacts of exposure to the pervasive environmental toxicant, inorganic arsenic (iAs), on human and fish health are well characterized and several lines of evidence suggest that some impacts can manifest years after exposure cessation. Using a developmental exposure protocol whereby zebrafish embryos were exposed to 0.5 and 1.5 mM iAs from 4-120 hours post fertilization (hpf) and then removed, we investigated the sustained effects of iAs on gene expression in the liver, survival, reproductive success, and susceptibility to iAs toxicity in the subsequent generation. Persistent exposure to iAs during development had substantial effects on the hepatic transcriptome, with 23% of all expressed genes significantly changed following developmental exposure. The gsto2 gene is involved in iAs metabolism and this gene was significantly downregulated in female livers 9 months after iAs was removed. Developmental exposure to 1.5 mM iAs, but not 0.5 mM, decreased survival by over 50% at 3 months of age. Adults that were developmentally exposed to 0.5 mM iAs had reduced mating success, but their offspring had no differences in observable aspects of development or their susceptibility to iAs toxicity. This demonstrates that developmental exposure of zebrafish to iAs reduces long-term survival, reproductive success and causes sustained changes to gsto2 expression in the liver.

Atherogenic Index as a Cardiovascular Biomarker in Mexican Workers from Marginalized Urban Areas Occupationally Exposed to Metals.

BACKGROUND: Cardiovascular disease (CVD) is one of the main causes of death and disability worldwide. The etiology of CVD is often associated with multiple risk factors, with environmental factors receiving considerable attention. Individuals with precarious jobs are among the groups most affected by chronic exposure to environmental pollutants. AIM: This study aimed to evaluate occupational exposure to heavy metals among individuals in precarious job settings and investigate atherogenic indices as biomarkers of cardiovascular risk. METHODS: A total of 137 workers participated in this cross-sectional study conducted in three work environments in San Luis Potosi, Mexico. Urine and blood samples were collected to assess metal exposure and biochemical profiles, including atherogenic indices. RESULTS: The results showed that workers in the brick sector exhibited the highest levels of metal exposure, particularly arsenic (44.06 µg/L), followed by stonecutters and garbage collectors (24.7 and 16.9 µg/L, respectively). Similarly, Castelli risk index (CRI) and the atherogenic index of plasma (AIP) were higher in brickmakers (3.883 and 0.499) compared to stonecutters (3.285 and 0.386) and garbage collectors (3.329 and 0.367). CONCLUSIONS: Evidence of exposure to heavy metals was observed in the three populations, in addition to the fact that individuals with greater exposure to arsenic also exhibited higher CRI and AIP.

Pollutants to pathogens: The role of heavy metals in modulating TGF-ß signaling and lung cancer risk.

Lung cancer is a malignant tumor that develops in the lungs due to the uncontrolled growth of aberrant cells. Heavy metals, such as arsenic, cadmium, mercury, and lead, are metallic elements characterized by their high atomic weights and densities. Anthropogenic activities, such as industrial operations and pollution, have the potential to discharge heavy metals into the environment, hence presenting hazards to ecosystems and human well-being. The TGF-ß signalling pathways have a crucial function in controlling several cellular processes, with the ability to both prevent and promote tumor growth. TGF-ß regulates cellular responses by interacting in both canonical and non-canonical signalling pathways. Research employing both in vitro and in vivo models has shown that heavy metals may trigger TGF-ß signalling via complex molecular pathways. Experiments conducted in a controlled laboratory environment show that heavy metals like cadmium and arsenic may directly bind to TGF-ß receptors, leading to alterations in their structure that enable the receptor to be phosphorylated. Activation of this route sets in motion subsequent signalling cascades, most notably the canonical Smad pathway. The development of lung cancer has been linked to heavy metals, which are ubiquitous environmental pollutants. To grasp the underlying processes, it is necessary to comprehend their molecular effect on TGF-ß pathways. With a particular emphasis on its consequences for lung cancer, this abstract delves into the complex connection between exposure to heavy metals and the stimulation of TGF-ß signalling.

Systematic review of studies on exposure to arsenic in drinking water and cognitive and neurobehavioral effects.

An association between exposure to arsenic (As) and neurologic and behavioral effects has been reported in some studies, but no systematic review is available of the evidence linking As in drinking water and neurobehavioral effects after consideration of study quality and potential confounding, with focus on low-level circumstances of exposure. We conducted a systematic review and reported it in compliance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, through a search of the databases PubMed, Web of Science, Scopus, and Embase. We included in the review the studies reporting results based on exposure from drinking water in humans. Endpoints were heterogeneous across studies, so we classified them into eight broad domains and developed an ad-hoc system to evaluate their methodological quality, based on three tiers. It was not possible to conduct meta-analysis because of the heterogeneity in exposure assessment and in the definition and assessment of outcomes. The search identified 18,518 articles. After elimination of duplicates and irrelevant articles, we retained 106 articles which reported results on As exposure and neurobehavioral effects, of which 22 reported risk estimates from exposure in drinking water (six among adults and 16 among children). None of the studies was conducted blindly. Among the studies in adults, two, which were conducted in highly exposed populations, were classified as high quality. These two studies were broadly consistent in reporting an association between exposure to As and decline in cognitive function; however, they provide no evidence of an association for exposure below 75 µg/L. The four lower-quality studies were based on populations with low exposure; these studies reported associations with inconsistent outcomes, few of which remained statistically significant after adjustment for multiple comparisons. Among the five high-quality studies of children, one reported an association between As in drinking water and intellectual function, whereas none of the other studies reported an association with different neurobehavioral indicators, after adjusting for potential confounders and multiple comparisons. Out of seven intermediate-quality studies, three reported an association with cognitive function or other outcomes; but sources of bias were not adequately controlled. The remaining studies were negative. The four low-quality studies did not contribute to the overall evidence because of methodological limitations. Our assessment of the available literature showed a lack of evidence for a causal association between exposure to As in drinking water and neurobehavioral effects. To clarify whether such an association exists, further studies prospectively evaluating changes in both the concentration of As in drinking water during the life course, and neurobehavioral outcomes, as well as appropriately controlling for potential confounders, are needed.

Effects of biodegradable microplastics on arsenic migration and transformation in paddy soils: a comparative analysis with conventional microplastics.

The combined pollution of microplastics (MPs) and arsenic (As) in paddy soils has attracted more attention worldwide. However, there are few comparative studies on the effects of biodegradable and conventional MPs on As migration and transformation. Therefore, conventional (polystyrene, polyethylene, polyvinyl chloride) and biodegradable (polybutadiene styrene, polylactic acid, polybutylene adipate terephthalate) MPs were selected to explore and demonstrate their influences and mechanism on As migration from paddy soils to overlying water and As speciation transformation through microcosmic experiment with measuring the changes of As chemical distribution, physicochemical indexes and microbial community in paddy soils. The results showed that biodegradable MPs enhanced As migration and transformation more effective than conventional MPs during 60 d. Biodegradable MPs indirectly increased the content of As(Ⅲ) and bioavailable As by changing the microbial community structure and affecting the biogeochemical cycles of carbon, nitrogen, sulfur and iron in soils, and promoted the As migration and transformation. PBS showed the strongest promoting effect, transforming to more As(Ⅲ) (11.43%) and bioavailable As (4.28%) than control. This helps to a better understanding of the effects of MPs on As biogeochemical cycle and to clarify the ecological and food safety risks of their combined pollution in soils.

Mechanistic insight into the intensification of arsenic toxicity to rice (Oryza sativa L.) by nanoplastic: Phytohormone and glutathione metabolism modulation.

In this study, nanoplastic (NPs) at environmentally relevant concentration (0.001% w/w) had no effect on the growth of rice, while significantly elevated the phytotoxicity of As (III) by 9.4-22.8% based on the endpoints of biomass and photosynthesis. Mechanistically, NPs at 0.001% w/w enhanced As accumulation in the rice shoots and roots by 70.9% and 24.5%, respectively. Reasons of this finding can was that (1) the co-exposure with As and NPs significantly decreased abscisic acid content by 16.0% in rice, with subsequent increasing the expression of aquaporin related genes by 2.1- to 2.7-folds as compared with As alone treatment; (2) the presence of NPs significantly inhibited iron plaque formation on rice root surface by 22.5%. We firstly demonstrated that "Trojan horse effect" had no contribution to the enhancement of As accumulation by NPs exposure. Additionally, NPs disrupted the salicylic acid, jasmonic acid, and glutathione metabolism, which subsequently enhancing the oxidation (7.0%) and translocation (37.0%) of in planta As, and reducing arsenic detoxification pathways (e.g., antioxidative system (28.6-37.1%), As vacuolar sequestration (36.1%), and As efflux (18.7%)). Our findings reveal that the combined toxicity of NPs and traditional contaminations should be considered for realistic evaluations of NPs.

'Environmental standard limit concentration' arsenic exposure is associated with anxiety, depression, and autism-like changes in early-life stage zebrafish.

Arsenic is a worldwide environmental pollutant that can impair human health. Previous studies have identified mental disorders induced by arsenic, but the environmental exposure concentrations in the early life stages associated with these disorders are poorly understood. In the present study, early-life stage zebrafish were used to explore the effects on mental disorders under 'environmental standard limit concentrations' arsenic exposures of 5, 10, 50, 150, and 500 µg/L. The results showed that arsenic exposure at these concentrations changed the locomotor behavior in larval zebrafish and was further associated with anxiety, depression, and autism-like behavior in both larval and juvenile zebrafish. Changes were noted at benchmark dose limit (BMDL) concentrations as low as 0.81 µg/L. Transcriptomics showed that immediate early genes (IEGs) fosab, egr1, egr2a, ier2b, egr3, and jund were decreased after arsenic exposure in larval and juvenile zebrafish. Nervous system impairment and anxiety, depression, and autism-like behaviors in early-life stage zebrafish at 'environmental standard limit concentrations' may be attributed to the downregulation of IEGs. These findings in zebrafish provided new experimental support for an arsenic toxicity threshold for mental disorders, and they suggest that low levels of environmental chemicals may be causative developmental factors for mental disorders.

Toxicogenomics of the Freshwater Oligochaete, Tubifex tubifex (Annelida, Clitellata), in Acute Water-Only Exposure to Arsenic.

A toxicogenomic approach was used for toxicity evaluation of arsenic in the aquatic environment, and differential gene expression was investigated from 24 h and 96 h water-only acute toxicity tests with the aquatic oligochaete, Tubifex tubifex (Annelida, Clitellata). Several toxicological endpoints (survival and autotomy) of the oligochaete and tissue residues were measured, and dose-response modelling of gene expression data was studied. A reference transcriptome of the aquatic oligochaete, T. tubifex, was reconstructed for the first time, and genes related to cell stress response (Hsc70, Hsp10, Hsp60, and Hsp83), energy metabolism (COX1), oxidative stress (Cat, GSR, and MnSOD), and the genes involved in the homeostasis of organisms (CaM, RpS13, and UBE2) were identified and characterised. The potential use of the genes identified for risk assessment in freshwater ecosystems as early biomarkers of arsenic toxicity is discussed.

Neurogenic Effects of Inorganic Arsenic and Cdk5 Knockdown in Zebrafish Embryos: A Perspective on Modeling Autism.

The exact mechanisms of the development of autism, a multifactorial neurological disorder, are not clear. The pathophysiology of autism is complex, and investigations at the cellular and molecular levels are ongoing to provide clarity. Mutations in specific genes have been identified as risk factors for autism. The role of heavy metals in the pathogenesis of autism is subject to many studies and remains debatable. Although no exact neuronal phenotypes have been identified linked to autistic symptoms, overproduction and reduction of specific neurons have been implicated. A growing literature on generating genetic and non-genetic models of autism aims to help with understanding mechanistic studies that can explain the complexity of the disorder. Both genetic and non-genetic methods of zebrafish have been used to model autism. For several human autism risk genes, validated zebrafish mutant models have been generated. There is growing evidence indicating a potential link between autism and inorganic arsenic exposure. We have previously shown that inorganic arsenic induces supernumerary spinal motor neurons via Sonic hedgehog (Shh) signaling pathway, and Cdk5 knockdown causes an overproduction of cranial and spinal motor neurons in zebrafish. Here, in this review, we provide a perspective on what these findings of neurogenic phenotypes mean in terms of dysregulated pathways of motor neuron development and their applicability to understanding cellular and molecular underpinnings of autism.