Single-cell investigation of lead toxicity from neurodevelopment to neurodegeneration: Current review and future opportunities.

Human exposure to the metal lead (Pb) is prevalent and associated with adverse neurodevelopmental and neurodegenerative outcomes. Pb disrupts normal brain function by inducing oxidative stress and neuroinflammation, altering cellular metabolism, and displacing essential metals. Prior studies on the molecular impacts of Pb have examined bulk tissues, which collapse information across all cell types, or in targeted cells, which are limited to cell autonomous effects. These approaches are unable to represent the complete biological implications of Pb exposure because the brain is a cooperative network of highly heterogeneous cells, with cellular diversity and proportions shifting throughout development, by brain region, and with disease. New technologies are necessary to investigate whether Pb and other environmental exposures alter cell composition in the brain and whether they cause molecular changes in a cell-type-specific manner. Cutting-edge, single-cell approaches now enable research resolving cell-type-specific effects from bulk tissues. This article reviews existing Pb neurotoxicology studies with genome-wide molecular signatures and provides a path forward for the field to implement single-cell approaches with practical recommendations.

Demyelination and Impaired Oligodendrogenesis in the Corpus Callosum Following Lead Exposure.

The corpus callosum is an oligodendrocyte-enriched brain region, replenished by newborn oligodendrocytes from oligodendrocyte progenitor cells (OPCs) in subventricular zone (SVZ). Lead (Pb) exposure has been associated with multiple sclerosis, a disease characterized by the loss of oligodendrocytes. This study aimed to investigate effects of Pb exposure on oligodendrogenesis in SVZ and myelination in corpus callosum. Adult female mice were used for a disproportionately higher prevalence of multiple sclerosis in females. Acute Pb exposure (one ip-injection of 27 mg Pb/kg as PbAc2 24 hrs before sampling) caused mild Pb accumulation in corpus callosum. Ex vivo assay using isolated SVZ tissues collected from acute Pb-exposed brains showed a diminished oligodendrogenesis in SVZ-derived neurospheres compared to controls. In vivo subchronic Pb exposure (13.5 mg Pb/kg by daily oral gavage 4 wks) revealed significantly decreased newborn BrdU+/MBP+ oligodendrocytes in corpus callosum, suggesting demyelination. Mechanistic investigations indicated decreased Rictor in SVZ OPCs, defective self-defense pathways, and reactive gliosis in corpus callosum. Given the interwined pathologies between multiple sclerosis and Alzheimers's disease, effect of Pb on myelination was evalued in AD-modeled APP/PS1 mice. Myelin MRI on mice following chronic exposure (1000 ppm Pb in drinking water as PbAc2 for 20 wks) revealed a profound demyelination in corpus callosum compared to controls. Immunostaining of choroid plexus showed diminished signalling molecule (Klotho, OTX2) expressions in Pb-treated animals. These observations suggest that Pb caused demyelination in corpus callosum, likely by disrupting oligodendrogenesis from SVZ OPCs. Pb-induced demyelination represents a crucial pathogenic pathway in Pb neurotoxicity, including multiple sclerosis.

Gut dysbiosis of Rana zhenhaiensis tadpoles after lead (Pb) exposure based on integrated analysis of microbiota and gut transcriptome.

Lead (Pb) is a ubiquitously detected heavy metal pollutant in aquatic ecosystems. Previous studies focused mainly on the response of gut microbiota to Pb stress, with less emphasis on gene expression in intestine, thereby limiting the information about impacts of Pb on intestinal homeostasis in amphibians. Here, microbial community and transcriptional response of intestines in Rana zhenhaiensis tadpoles to Pb exposure were evaluated. Our results showed that 10 µg/L Pb significantly decreased bacterial diversity compared to the controls by the Simpson index. Additionally, 1000 µg/L Pb exposure resulted in a significant reduction in the abundance of Fusobacteriota phylum and Cetobacterium genus but a significant expansion in Hafnia-Obesumbacterium genus. Moreover, transcriptome analysis revealed that about 90 % of the DEGs (8458 out of 9450 DEGs) were down-regulated in 1000 µg/L Pb group, mainly including genes annotated with biological functions in fatty acid degradation, and oxidative phosphorylation, while up-regulated DEGs involved in metabolism of xenobiotics by cytochrome P450. The expression of Gsto1, Gsta5, Gstt4, and Nadph showed strong correlation with the abundance of genera Serratia, Lactococcus, and Hafnia-Obesumbacterium. The findings of this study provide important insights into understanding the influence of Pb on intestinal homeostasis in amphibians.

Potentials of dietary fiber and polyphenols in whole grain wheat flour to release the liver function and intestinal tract injury in lead-induced mice.

The presence of lead as an environmental pollutant is widespread. However, safe and effective treatments for the resulting intestinal and liver damage from high levels of lead exposure remain limited. The study aimed to investigate the protective effects of dietary fiber and polyphenols in whole grain wheat flour on lead-induced mice. The results indicated that the daily intake of 12 mg of polyphenols, 0.5 g of dietary fiber, and their combination effectively reduced blood and liver lead accumulation by approximately 50 % in mice exposed to lead, while also mitigating lead-induced oxidative stress though a reduction in malondialdehyde levels and an enhancement in antioxidant enzyme activities including superoxide dismutase, catalase, and glutathione peroxidase. Furthermore, all three treatments enhanced cytokine secretion with the combined treatment exhibiting the highest efficacy. Specifically, the combination treatment decreased tumor necrosis factor-α and interleukin 1ß by 56.78 %, 47.86 % in intestinal tissue while increasing increased interleukin 4 and interleukin 10 by 81.84 %, 145.14 %. Additionally, it promoted the expression of tight junction proteins like Zonula occludens-1, Occludin and Claudin-1. The study presented a potential strategy for alleviating liver and intestinal tract damage from high-dose lead exposure.

Lead stabilization and remediation strategy with soil amendment in situ immobilization in contaminated range lands.

In situ immobilization is a potential approach that can be used to remediate low-to-medium levels of heavy-metal in contaminated-soil. There is little known about how modifications to soil characteristics may affect Pb's release from soil. The four different amendments, triple-superphosphate and attapulgite were combined in Ad-1; zeolite and triple-superphosphate were in Ad-2; hydroxyapatite and humus were in Ad-3; and nano-carbon. These amendments are mostly made of phyllosilicate minerals, humus, base minerals, and nano-carbon, respectively. Results revealed that the test amendments' maximal Pb-adsorption capacity varied from 7.47 to 17.67 mg g-1. Surface precipitation and ion-exchange were found to be the main mechanisms for Pb-adsorption by Ad-1 and Ad-2, while Ad-3 and Ad-4 were promising among the all, according to analysis of the modifications both before and after Pb loading. When the pH dropped (7-1) or the ion-strength rose (0-0.2 M), there was a discernible rise in the Pb-desorption percentages from the amendments. It was determined that Ad-3 and Ad-4 were more effective in situ immobilizing lead in contaminated-soils because of their high adsorption capacities (12.82 and 17.67 mg g-1) and low-desorption percentages (4.46-6.23%) at ion-strengths of 0.01-0.1 mol L-1 and pH levels ranging from 5 to 7.

This study pioneers a comprehensive exploration into the efficacy of novel soil amendments, Ad-3 and Ad-4 crafted from phyllosilicate minerals, humus, base minerals, and nano-carbon, showcasing their unprecedented potential in mitigating lead pollution. By delving into the intricate mechanisms of lead adsorption and desorption within treated soils, this research fills a critical gap in understanding how modifications to soil characteristics can influence the secondary release of lead, thus providing essential insights for tailored in situ remediation strategies to safeguard both plant and human health in lead-endangered environments.

Enhanced adsorption of Pb2+ by the oxygen-containing functional groups enriched activated carbon.

Lead is one of the primary pollutants found in water and poses significant toxicity risks to humans; thus, it is necessary to investigate techniques for removing it economically and efficiently. In order to enhance the removal capacity of Pb2+, coconut shell-based activated carbon (AC) was modified with introducing oxygen-containing functional groups (OFGs) via nitric acid (HNO3) or hydrogen peroxide (H2O2) modification in this study. The characterization results show that after oxidation treatment, the content of OFGs increased, and the textural properties of the samples do not change significantly. This indicates that the modification conditions used in this study effectively introduced OFGs while avoiding the adverse effects on physical adsorption ability of AC caused by oxidation treatment. The Pb2+ adsorption capacities of the AC modified with 10 M HNO3 and 30 wt.% H2O2 were 4.26 and 3.64 times that of the pristine AC, respectively. The experimental data can be well fitted using the Langmuir isotherm model and the Elovich kinetic model, suggesting that the adsorption of Pb2+ on AC belongs to single-layer adsorption, and chemical adsorption dominates the adsorption process. In summary, the hydrothermal-assisted HNO3/H2O2-modified coconut shell-based AC shows great potential in efficiently removing Pb2+ from solutions, offering a solution for utilizing coconut shell waste.

DNA damage and ALAD polymorphism in high blood lead (Pb) levels of pregnant women attending a tertiary care teaching hospital.

Background: Pregnant women are particularly vulnerable to lead toxicity due to increased absorption and decreased elimination of lead from their bodies. The δ-aminolevulinic acid dehydratase (ALAD) gene plays a crucial role in lead metabolism, and its polymorphisms have been implicated in modifying the susceptibility to lead toxicity. Methods: A cross-sectional study was conducted involving 90 pregnant women and blood samples were collected to measure blood lead levels (BLL) and assessed DNA damage using the comet assay. ALAD polymorphisms were genotyped using PCR-RFLP analysis with MspI restriction enzyme. Statistical analysis, including chi-square tests, logistic regression, and correlation analysis, was performed to determine associations between ALAD polymorphisms, BLL, and DNA damage. Results: From 90 pregnant women the participants, 16 had high BLL (≥5 µg/dL), while the remaining 74 had normal levels (<5 µg/dL). The ALAD 1-2 genotype was found to be significantly associated with high BLL (p < 0.001). Pregnant women with the ALAD 1-2 genotype exhibited higher levels of DNA damage compared to those with other genotypes (p < 0.001). Furthermore, a positive correlation was observed between the transfer of lead concentration from mother to infant and DNA damage severity (r = 0.511, p < 0.001). Conclusions: The combination of comet assay and polymorphism analysis offers a comprehensive approach to understanding the impact of lead exposure during pregnancy. These findings underscore the urgent need for effective regulatory measures to reduce lead exposure in the environment and mitigate its adverse effects of lead on maternal and child health.

Translational toxicoepigenetic Meta-Analyses identify homologous gene DNA methylation reprogramming following developmental phthalate and lead exposure in mouse and human offspring.

Although toxicology uses animal models to represent real-world human health scenarios, a critical translational gap between laboratory-based studies and epidemiology remains. In this study, we aimed to understand the toxicoepigenetic effects on DNA methylation after developmental exposure to two common toxicants, the phthalate di(2-ethylhexyl) phthalate (DEHP) and the metal lead (Pb), using a translational paradigm that selected candidate genes from a mouse study and assessed them in four human birth cohorts. Data from mouse offspring developmentally exposed to DEHP, Pb, or control were used to identify genes with sex-specific sites with differential DNA methylation at postnatal day 21. Associations of human infant DNA methylation in homologous mouse genes with prenatal DEHP or Pb were examined with a meta-analysis. Differential methylation was observed on 6 cytosines (adjusted-p < 0.05) and 90 regions (adjusted-p < 0.001). This translational approach offers a unique method that can detect conserved epigenetic differences that are developmentally susceptible to environmental toxicants.

Pb uptake, accumulation, and translocation in plants: Plant physiological, biochemical, and molecular response: A review.

Lead (Pb) is a highly toxic contaminant that is ubiquitously present in the ecosystem and poses severe environmental issues, including hazards to soil-plant systems. This review focuses on the uptake, accumulation, and translocation of Pb metallic ions and their toxicological effects on plant morpho-physiological and biochemical attributes. We highlight that the uptake of Pb metal is controlled by cation exchange capacity, pH, size of soil particles, root nature, and other physio-chemical limitations. Pb toxicity obstructs seed germination, root/shoot length, plant growth, and final crop-yield. Pb disrupts the nutrient uptake through roots, alters plasma membrane permeability, and disturbs chloroplast ultrastructure that triggers changes in respiration as well as transpiration activities, creates the reactive oxygen species (ROS), and activates some enzymatic and non-enzymatic antioxidants. Pb also impairs photosynthesis, disrupts water balance and mineral nutrients, changes hormonal status, and alters membrane structure and permeability. This review provides consolidated information concentrating on the current studies associated with Pb-induced oxidative stress and toxic conditions in various plants, highlighting the roles of different antioxidants in plants mitigating Pb-stress. Additionally, we discussed detoxification and tolerance responses in plants by regulating different gene expressions, protein, and glutathione metabolisms to resist Pb-induced phytotoxicity. Overall, various approaches to tackle Pb toxicity have been addressed; the phytoremediation techniques and biochar amendments are economical and eco-friendly remedies for improving Pb-contaminated soils.

[Blocking Effects of Foliar Conditioners on Cadmium, Arsenic, and Lead Accumulation in Wheat Grain in Compound-contaminated Farmland].

Heavy metal contamination of soil has become a hot issue of social concern due to its impact on the safety of agricultural products in recent years. Wheat is one of the most dominant staple food crops worldwide and has become a major source of toxic metals in human diets. Foliar application was considered to be a more efficient and economical method of heavy metal remediation. Field experiments were carried out in Cd-, As-, and Pb-contaminated farmland soils. The effects of foliar conditioners on the accumulation of Cd, As, and Pb in wheat grains were investigated after being sprayed with Zn (0.2% ZnSO4), Mg (0.4% MgSO4), and Mn (0.2% MnSO4) separately and in combination. Thus, the effective foliar conditioners were selected to block the accumulation of Cd, As, and Pb in wheat grains grown in combined heavy metal-contaminated farmland in north China. The results showed that, compared with that in the control, the Cd, As, and Pb contents in wheat grains of the Zn+Mg+Mn foliar treatment were significantly decreased by 18.96%, 23.87%, and 51.31%, respectively, and TFgrain/straw decreased by 14.62%, 27.73%, and 47.70%, respectively. Thus, spraying the compound foliar conditioner of Zn+Mg+Mn could effectively reduce heavy metal accumulation in wheat grains through inhibition translocation of those metals from stem leaves to grain. In addition, the results indicated that Cd and As were mainly distributed at the central endosperm (34.08%-37.08%), whereas Pb was primarily distributed at the pericarp and seed coat (27.78%) of the wheat grain. Compared with that in the control, spraying the compound foliar conditioner of Zn+Mg+Mn extremely decreased Cd and As accumulation in the aleurone layer of the wheat grain by 81.10% and 82.24%, respectively. Except for the pericarp, seed coat, and central endosperm layers, the Pb content in each grain layer was dramatically decreased by 42.85% to 91.15%. There was only a significant negative correlation between heavy metal content and Zn content in the aleurone layer (P2) of wheat flour. In summary, the accumulation of Cd, As, and Pb in wheat grains, especially in the aleurone layer, could be effectively reduced by foliar conditioner application at the jointing, booting, and early filling stages of wheat, separately. Furthermore, besides the foliar treatment, removing wheat bran to reduce Cd contamination in wheat grains is highly recommended to ensure the safe production of wheat.

Lead induced genotoxicity and hepatotoxicity in zebrafish (Danio rerio) at environmentally relevant concentration: Nrf2-Keap1 regulated stress response and expression of biomarker genes.

Genotoxic and hepatotoxic potentials of Pb at an environmentally relevant concentration (5 ppm) in zebrafish were investigated in the present study. Erythrocytic nuclear abnormality tests revealed the increased frequencies of abnormal erythrocytes after Pb exposure, indicating a strong genotoxic potential of Pb. Multiple stress-related parameters were further evaluated in liver, the major detoxifying organ. Pb caused increased production of ROS, which in turn caused severe oxidative stress. As a result, lipid peroxidation was increased, whereas reduced glutathione level and catalase activity was decreased. Alterations in liver histoarchitecture also served as evidence of Pb-induced hepatotoxicity. Pb-induced ROS stress triggered upregulation of Nrf2, Nqo1, Ho1; downregulation of Keap1, and altered mRNA expressions of Mn-sod, Cu/Zn-sod, gpx1, cyp1a, ucp2 suggesting involvement of Nrf2-Keap1-ARE signaling in cellular defence. Nrf2-keap1 is a sensitive biomarker of Pb-induced ROS stress. Overexpression of Hsp70 and other genes in hepatocytes might help cell survival under oxidative stress generation.

Environmentally relevant lead alters nuclear integrity in erythrocytes and generates oxidative stress in liver of Anabas testudineus: Involvement of Nrf2-Keap1 regulation and expression of biomarker genes.

Genotoxic and hepatotoxic effects of lead (Pb) on a freshwater fish, climbing perch (Anabas testudineus) were studied at an environmentally relevant concentration (43.3 ppm). The genotoxic potential of Pb was confirmed by micronucleus study, with increased frequencies of erythrocytic nuclear alterations like lobed, blebbed, notched, fragmented, and micronuclei were observed in erythrocytes in treated groups as compared to control. Inorganic Pb induces oxidative stress which is a consequence of elevated level of Reactive Oxygen Species. Hepatotoxicity was assessed both by the oxidative stress and cellular responses that emerged due to the toxic assault of Pb in the liver, the most important detoxifying organ. Upregulation of xenobiotic metabolizing enzyme like catalase was evident after 15, 30, and 90 days of exposure, and a profound effect was observed on 30th days. The level of lipid peroxidation and reduced glutathione was increased after Pb exposure. Histoarchitectural damages of liver were distinctly evident in treated fish. Western blot analysis confirmed the expressional alterations of stress-responsive marker proteins like Nrf2, Keap1, Hsp70, and Nqo1. Pb exposure resulted in increased expression of Hsp70, Nrf2, and Nqo1, whereas Keap1 was downregulated, suggesting the involvement of Nrf2-Keap1 regulation as a cytoprotective mechanism against Pb toxicity.

Chronic Pb exposure impairs learning and memory abilities by inhibiting excitatory projection neuro-circuit of the hippocampus in mice.

Lead (Pb) is an environmental neurotoxic metal. Chronic Pb exposure causes behavioral changes in humans and rodents, such as dysfunctional learning and memory. Nevertheless, it is not clear whether Pb exposure disrupts the neural circuit. Thus, here we aim at investigating the effects the chronic Pb exposure on neural-behavioral and neural circuits in mice from prenatal to postnatal day (PND) 63. Pregnant mice and their male offspring were treated with Pb (150 ppm) until postnatal day 63. In this study, several behavior tests and Golgi-Cox staining methods were used to assess spatial memory ability and synaptogenesis. Virus-based tracing systems and immunohistochemistry assays were used to test the relevance of chronic Pb exposure with disrupted neural circuits. The behavioral experiments and Golgi-Cox staining results showed that Pb exposure impaired spatial memory and spine density in mice. The virus tracing results revealed that the Entorhinal cortex (EC) neurons could be directly projected to Cornuammonis 1 (CA1) and Dentate gyrus (DG), forming a critical circuit inhibited, in either a direct or indirect way, by Pb invasion. In addition, excitatory neural input from EC（labeled with CaMKII）to CA1 and DG was significantly attenuated by Pb exposure. In conclusion, our data indicated that Pb significantly impaired the excitatory connections from EC to the hippocampus (CA1 and DG), providing a novel neuro-circuitry basis for Pb neurotoxicity.

Far-Infrared Ameliorates Pb-Induced Renal Toxicity via Voltage-Gated Calcium Channel-Mediated Calcium Influx.

Far-infrared (FIR), characterized by its specific electromagnetic wavelengths, has emerged as an adjunctive therapeutic strategy for various diseases, particularly in ameliorating manifestations associated with renal disorders. Although FIR was confirmed to possess antioxidative and anti-inflammatory attributes, the intricate cellular mechanisms through which FIR mitigates lead (Pb)-induced nephrotoxicity remain enigmatic. In this study, we investigated the effects of FIR on Pb-induced renal damage using in vitro and in vivo approaches. NRK52E rat renal cells exposed to Pb were subsequently treated with ceramic-generated FIR within the 9~14 µm range. Inductively coupled plasma mass spectrometry (ICP-MS) enabled quantitative Pb concentration assessment, while proteomic profiling unraveled intricate cellular responses. In vivo investigations used Wistar rats chronically exposed to lead acetate (PbAc) at 6 g/L in their drinking water for 15 weeks, with or without a concurrent FIR intervention. Our findings showed that FIR upregulated the voltage-gated calcium channel, voltage-dependent L type, alpha 1D subunit (CaV1.3), and myristoylated alanine-rich C kinase substrate (MARCKS) (p < 0.05), resulting in increased calcium influx (p < 0.01), the promotion of mitochondrial activity, and heightened ATP production. Furthermore, the FIR intervention effectively suppressed ROS production, concurrently mitigating Pb-induced cellular death. Notably, rats subjected to FIR exhibited significantly reduced blood Pb levels (30 vs. 71 µg/mL; p < 0.01), attenuated Pb-induced glomerulosclerosis, and enhanced Pb excretion compared to the controls. Our findings suggest that FIR has the capacity to counteract Pb-induced nephrotoxicity by modulating calcium influx and optimizing mitochondrial function. Overall, our data support FIR as a novel therapeutic avenue for Pb toxicity in the kidneys.

The Association among Urinary Lead and Cadmium, Serum Adiponectin, and Serum Apoptotic Microparticles in a Young Taiwanese Population.

Previous studies reported that lead (Pb) and cadmium (Cd) exposure are linked to changes in serum adiponectin; an adipokine that promotes glycolysis and inhibits gluconeogenesis to regulate glucose metabolism. However, no study has ever explored the relationship between exposure to these two heavy metals and adiponectin in adolescents and young adults. Additionally, the role of adiponectin in the relationship between Pb and Cd exposure and vascular endothelial cell apoptosis has never been investigated. In this study, 724 Taiwanese participants, aged 12 to 30 years, were enrolled to investigate the association among urinary lead and cadmium, serum adiponectin, and apoptotic microparticles (CD31+/CD42a-, CD31+/CD42a+, and CD14). The results of the current study revealed a statistically significant inverse association between urine Pb and Cd levels and adiponectin levels, as well as a positive association with apoptotic microparticles (CD31+/CD42a-, CD31+/CD42a+, and CD14). Adiponectin was also inversely correlated with CD31+/CD42a- and CD31+/CD42a+. Moreover, when subjects with both Pb and Cd levels above the 50th percentile were compared to those below it, the former group exhibited the lowest average adiponectin value. Additionally, a more pronounced positive association between heavy metals and apoptotic microparticles (CD31+/CD42a- and CD31+/CD42a+) was observed when adiponectin levels were lower. Furthermore, an interaction between adiponectin and heavy metals was identified in the relationship between these metals and CD31+/CD42a-. In conclusion, these findings suggest that Pb and Cd exposure may have an adverse effect on adiponectin, and it may play a role in the link between heavy metal exposure and the dysfunction of vascular endothelial cells. Future studies are needed to establish whether a causal relationship exists.

Unveiling Potential Neurotoxic Mechansisms: Pb-Induced Activation of CDK5-p25 Signaling Axis in Alzheimer's Disease Development, Emphasizing CDK5 Inhibition and Formation of Toxic p25 Species.

Alzheimer's disease (AD) is a complex neurodegenerative disorder with an etiology influenced by various genetic and environmental factors. Heavy metals, such as lead (Pb), have been implicated in AD pathogenesis, but the underlying mechanisms remain poorly understood. This study investigates the potential neurodegenerative role of Pb and amyloid ß peptides (1-40 and 25-35) via their interaction with cyclin-dependent kinase 5 (CDK5) and its activator, p25, in an attempt to unravel the molecular basis of Pb-induced neurotoxicity in neuronal cells. To this end, a CDK5 inhibitor was utilized to selectively inhibit CDK5 activity and investigate its impact on neurodegeneration. The results revealed that Pb exposure led to elevated Pb uptake (56.7% at 15 µM Pb) and disturbances in intracellular calcium (19.6% increase upon Pb treatment). The results revealed a significant decrease in total antioxidant capacity (by 88.6% upon Pb treatment) and also elevation in protein carbonylation (by 26.2% upon Pb and Aßp's combination treatment), indicative of oxidative damage, suggesting an impaired cellular defence against oxidative stress and elevated DNA oxidative damage (178 pg/ml and 182 pg/ml of 8-OH-dG upon Pb and All treatment). Additionally, dysregulations in levels of calpain, p25-35 and CDK5 are observed and markers associated with antioxidant metabolism (phospho-Peroxiredoxin 1), DNA damage responses (phospho-ATM and phospho-p53), and nuclear membrane disruption (phospho-lamin A/C) were observed, supporting the role of Pb-induced CDK5-p25 signaling in AD pathogenesis. These findings shed light on the intricate molecular events underlying Pb-induced neurotoxicity and provide valuable insights into the mechanisms that contribute to AD development.

[Accumulation Characteristics, Sources, and Health Risks of Soil Lead of Urban Parks in Beijing].

Urban parks have multiple functions such as social culture, economy, and environmental services during urban development. The rapid development of cities and economy may lead to the accumulation of heavy metals in the soil of urban parks, which may threaten human health. A total of 140 soil samples were collected in 32 typical parks in Beijing. The accumulation characteristics of Pb in the soil of urban parks were analyzed using the single-factor pollution and geo-accumulation indices. The sources of Pb pollution in soils were quantitatively analyzed using the stable isotope of Pb, and the health risk was assessed using the probabilistic risk assessment method based on Monte Carlo simulation. The results showed that the geometric mean of Pb in soils of urban parks in Beijing was 38.63 mg·kg-1, which was 1.48 times the background value. However, it did not exceed the risk screening value(GB 36600-2018). The accumulation of soil Pb in urban parks increased with the increase in the proximity between the park and the central urban area and the increase in the establishment time. The soil Pb pollution index of 2 ring, 2-4 ring, and 4-6 ring parks were 0.16, 0.10, and 0.09, which did not reach the pollution level, and the geo-accumulation indices were 0.80, 0.07, and -0.31, respectively. Except for the no-moderate pollution level in ring 2 and ring 2 to ring 4, the other rings did not reach the pollution level. The sources of Pb pollution in urban parks were coal combustion, road dust, and paint, with the contributions of 45.4%, 19.6%, and 13.9%, respectively. The 95% quantiles of hazard index(HI) of soil Pb in the park for different age groups were 1.11E-01, 8.57E-02, 6.39E-02, 1.64E-02, 1.36E-02, 1.26E-02, 1.64E-02, and 1.78E-02, respectively, which indicated that there was no potential non-carcinogenic risk(HI<1). Exposure duration was the most sensitive to non-carcinogenic risks in people aged 0-18 years, and soil Pb concentration was the most sensitive to non-carcinogenic risks in people aged 18-80 years. The increase in body weight often reduced the non-carcinogenic risks. These results can provide theoretical basis for soil environmental risk control in urban parks.

The Exposure to Lead (Pb) Exacerbates Immunological Abnormalities in BTBR T+ Itpr3tf/J Mice through the Regulation of Signaling Pathways Relevant to T Cells.

Autism spectrum disorder (ASD) is a common neurodevelopmental illness characterized by abnormal social interactions, communication difficulties, and repetitive and limited behaviors or interests. The BTBR T+ Itpr3tf/J (BTBR) mice have been used extensively to research the ASD-like phenotype. Lead (Pb) is a hazardous chemical linked to organ damage in the human body. It is regarded as one of the most common metal exposure sources and has been connected to the development of neurological abnormalities. We used flow cytometry to investigate the molecular mechanism behind the effect of Pb exposure on subsets of CD4+ T cells in the spleen expressing IFN-γ, T-bet, STAT1, STAT4, IL-9, IRF4, IL-22, AhR, IL-10, and Foxp3. Furthermore, using RT-PCR, we studied the effect of Pb on the expression of numerous genes in brain tissue, including IFN-γ, T-bet, STAT1, STAT4, IL-9, IRF4, IL-22, AhR, IL-10, and Foxp3. Pb exposure increased the population of CD4+IFN-γ+, CD4+T-bet+, CD4+STAT1+, CD4+STAT4+, CD4+IL-9+, CD4+IRF4+, CD4+IL-22+, and CD4+AhR+ cells in BTBR mice. In contrast, CD4+IL-10+ and CD4+Foxp3+ cells were downregulated in the spleen cells of Pb-exposed BTBR mice compared to those treated with vehicle. Furthermore, Pb exposure led to a significant increase in IFN-γ, T-bet, STAT1, STAT4, IL-9, IRF4, IL-22, and AhR mRNA expression in BTBR mice. In contrast, IL-10 and Foxp3 mRNA expression was significantly lower in those treated with the vehicle. Our data suggest that Pb exposure exacerbates immunological dysfunctions associated with ASD. These data imply that Pb exposure may increase the risk of ASD.

Enhanced lead phytoextraction and soil health restoration through exogenous supply of organic ligands: Geochemical modeling".

Phytoremediation of lead (Pb) contaminated soil is a green technology to reduce Pb exposure and root exudates-derived organic acids play a vital role in this treatment process. In this study, Pb hyperaccumulator Pelargonium hortorum was chosen to investigate root-induced organic acid secretions and their subsequent role in Pb phytoextraction. In the first step, root exudation of P. hortorum was investigated in hydroponic experiments (0.2X Hoagland solution) under control and Pb stress conditions. Possible chemical interactions between Pb and the observed root exudates were then analyzed using Visual MINTEQ modeling. In the next step, the effects of the exogenous application of organic acids on Pb phytoextraction and soil enzymatic activities were studied in a pot experimental setup. Results indicated significant exudation of malic acid > citric acid > oxalic acid > tartaric acid in root exudates of P. hortorum under 50 mg L-1 Pb. Visual MINTEQ modeling results revealed that organic acids directly affect Pb dissolution in the nutrient solution by modulation of solution pH. Experimental results revealed that malic acid and citric acid significantly increased available Pb contents (7.2- and 6.7-folds) in the soil with 1500 mg kg-1 Pb contamination. Whereas, in shoot and root, the highest increase in Pb concentration was observed with citric acid (2.01-fold) and malic (3.75-fold) supplements, respectively. Overall, Pb uptake was notably higher when malic acid was applied (2.8-fold) compared to other organic acids, followed by citric acid (2.7-fold). In the case of soil enzymatic activities, oxalic acid significantly improved dehydrogenase, alkaline phosphatase, and microbial biomass by 1.6-, 1.4- and 1.3-folds, respectively. The organic acids were successful in reviving enzyme activity in Pb-contaminated soil, and might thus be used for long-term soil regeneration.

Toxicity and sublethal effects of lead (Pb) intake on honey bees (Apis mellifera).

Heavy metal pollution is becoming a worldwide problem affecting pollinators. The massive use of lead (Pb), the most harmful metal for the biosphere, in industries has increased the risk for honey bees. Pb exerts toxicity on living organisms inducing mainly oxidative stress. We assessed the toxicity and sublethal effects of Pb ingestion on protein content, catalase (CAT) activity, fat content and fatty acid (FA) profile of honey bee workers (Apis mellifera L.) under different nutritional conditions during chronic exposure tests. The LD50 was 15.13 ± 6.11 µg Pb2+/bee, similar to other reports. A single oral sublethal dose of 15 µg of Pb2+ affected the survival of bees fed with sugary food for ten days after Pb ingestion while supplementing the diet with bee bread improved Pb tolerance. The highest protein content was found in bees fed with the sugar paste and bee bread diet without Pb. CAT activity tended to decrease in bees of Pb groups independently of diet. Fat content was not affected by the diet type received by bees or Pb ingestion, but the FAs profile varied according to the nutritional quality of the diet. The results highlight that a single sublethal dose of Pb negatively affected the body proteins of bees despite the nutritional condition but did not disturb the FAs profile of workers. Nutrition plays an important role in preventing Pb-induced toxicity in honey bees.