Metal Mixtures Research Articles

Association between essential metals, adherence to healthy lifestyle behavior, and ankle-brachial index

BackgroundAnkle-brachial index (ABI) is a noninvasive diagnostic method for peripheral arterial disease (PAD) and a predictor of cardiovascular events. ObjectiveThe present study aimed to evaluate the association between individual or combined essential metals and ABI, as well as assess the collective impact of essential metals when coupled with healthy lifestyle on ABI. MethodsA total of 2865 participants were recruited in Wuhan Tongji Hospital between August 2018 and March 2019. Concentrations of essential metals in urine were measured by inductively coupled plasma mass spectrometer. ResultsThe results of general linear regression models demonstrated that after adjusting for confounding factors, there was a positive association between ABI increase and per unit increase of log 10-transformed, creatinine-corrected urinary Cr (β (95 % CI): 0.010 (0.004, 0.016), PFDR = 0.007), Fe (β (95 % CI): 0.010 (0.003, 0.017), PFDR = 0.018), and Co (β (95 % CI): 0.013 (0.005, 0.021), PFDR = 0.007). The WQS regression revealed a positive relationship between the mixture of essential metals and ABI (β (95 % CI): 0.006 (0.003, 0.010), P < 0.001), with Cr and Co contributing most to the relationship (weighted 45.48 % and 40.14 %, respectively). Compared to individuals with unfavorable lifestyle and the lowest quartile of Cr, Fe and Co, those with favorable lifestyle and the highest quartile of Cr, Fe and Co exhibited the most increase in ABI (β (95 % CI): 0.030 (0.017, 0.044) for Cr, β (95 % CI): 0.027 (0.013, 0.040) for Fe, and β (95 % CI): 0.030 (0.016, 0.044) for Co). ConclusionIn summary, our study indicates that adequate essential metal intake together with healthy lifestyle behaviors perform crucial roles in PAD protection.

Association Between Exposure to Multiple Toxic Metals in Follicular Fluid and the Risk of PCOS Among Infertile Women: The Mediating Effect of Metabolic Markers.

Polycystic ovary syndrome (PCOS) severely affects women's fertility and accompanies serious metabolic disturbances, affecting 5%-20% of women of reproductive age globally. We previously found that exposure to toxic metals in the blood raised the risk of PCOS, but the association between exposure to toxic metals and the risk of PCOS in the follicular fluid, the microenvironment for oocyte growth and development in females, and its effect on metabolism has not been reported. This study aimed to evaluate the associations between the concentrations of cadmium (Cd), mercury (Hg), barium (Ba) and arsenic (As) in FF and the risk of PCOS, and to explore the mediating effect of metabolic markers in FF on the above relationship. We conducteda case-control study, including 557 women with PCOS and 651 controls. Ba, Cd, Hg and As levels in FF were measured by ICP-MS, metabolites levels in FF was measured by LC-MS/MS among 168 participants randomly selected from all the participants. Logistic regression models were used to assess the association of a single metal level with the PCOS risk, and linear regression models were used to assess the relationships of a single metal level with clinical phenotype parameters and metabolites levels. Combined effect of metals mixture levels on the risk of PCOS were assessed via weighted quantile sum (WQS) regression and bayesian kernel machine regression (BKMR). Medication analysis was performed to explore the role of metabolic markers on the relationship of toxic metals levels with the risk of PCOS. The exposure levels of Cd, Hg, Ba and As in FF were all positively and significantly associated with the PCOS risk (with respect to the highest vs. lowest tertile group: OR = 1.57, 95% CI = 1.17 ~ 2.12 for Cd, OR = 1.69, 95% CI = 1.22 ~ 2.34 for Hg, OR = 1.76, 95% CI = 1.32 ~ 2.34 for Ba, OR = 1.42, 95% CI = 1.05 ~ 1.91 for As). In addition, levels of metal mixture also significantly correlated with the risk of PCOS, Cd level contributed most to it. Moreover, we observed significant positive relationships between Cd level and LH (β = 0.048, 95% CI = 0.002 ~ 0.094), T (β = 0.077, 95% CI = 0.029 ~ 0.125) and HOMA-IR value (β = 0.060, 95% CI = 0.012 ~ 0.107), as well as Hg level with LH, FSH/LH ratio and TC. Furthermore, we revealed that estrone sulfate, LysoPE 22:6 and N-Undecanoylglycine were significantly and positively mediating the association between Cd level and the risk of PCOS (with mediated proportion of 0.39, 0.24 and 0.35, respectively), and between Hg level and the risk of PCOS (with mediated proportion of 0.29, 0.20 and 0.46, respectively). These highly expressed metabolites significantly enriched in the fatty acid oxidation, steroid hormone biosynthesis and glycerophospholipids metabolism, which may explain the reason why the levels of Cd and Hg in FF associated with the phenotype of PCOS. Ba and As in FF was not found the above phenomenon. Our results suggested that exposure to multiple toxic metals (Cd, Hg, Ba and As) in FF associated with the increased risk of PCOS, Cd was a major contributor. Levels of Cd and Hg in FF significantly associated with the phenotype of PCOS. The above association may result from that Cd and Hg in FF related with the disturbance of fatty acid oxidation, steroid hormone biosynthesis and the glycerophospholipids metabolism.

Machine learning approaches for simultaneous spectrophotometric determination of heavy metal ions in water samples

In this study, the simultaneous determination of Co, Cd, Ni, Cu, and Pb was carried out as a color complex with 4-(2-pyridylazo) resorcinol in an aqueous solution under the assesting of machine learning. A partial least-squares multivariate linear regression and artificial neuron network for the analysis of mixtures of metals were developed. MATLAB is a powerful software machine learning program that was used to support matrix calculations and displays. The benefit of MATLAB in the construction of the machine learning model allows the development of a rapid and highly effective analysis of multiple components in the mixtures without separation and enrichment. For individual determinations, the working ranges were discovered as the important information for choosing the initial concentration of each heavy metal in a mixture, r. The results of analysis of Ni2+, Pb2+, and Cd2+ by two methods Partial Least Squares - PLS and Artificial Neural Networks - ANN are sensitive and accurate for simultaneous determination of the concentration of these ions in the synthesis mixture with a high regression coefficient of 0.993, respectively, 0.997, 0.997 for Ni2+, Pb2+ and Cd2+. As for Cu2+ and Co2+, the accuracy is higher when using the ANN method.

Unraveling the link between heavy metals, perfluoroalkyl substances and depression: Insights from epidemiological and bioinformatics strategies

Heavy metals and per- and polyfluoroalkyl substances (PFASs) have become particularly important when studying the development of depression, a common illness that severely restricts psychosocial functioning and diminishes quality of life. Therefore, the potential joint effects of heavy metal and PFAS exposure on depression, as well as the underlying mechanisms involved, were investigated by using integrated epidemiological and bioinformatic approaches in the present study. A thorough analysis of 7301 samples from the National Health and Nutrition Examination Survey (NHANES) cycles that occurred between 2005 and 2018 was performed. Single-exposure studies have shown that cadmium exposure is positively associated with depression, whereas perfluorooctanesulfonic acid (PFOS) exposure and perfluorodecanoic acid (PFDE) exposure are negatively associated with depression. Furthermore, the Bayesian kernel machine regression (BKMR) and quantile g-computation (QGcomp) models were employed to investigate the collective impact of exposure to mixed metals on depression. Cadmium emerged as the principal contributor to depression. Moreover, the addition of PFAS to the metal mixture had an antagonistic effect on depression, with PFOS having the most prominent influence. Analysis of the effects of co-exposure to cadmium and PFOS confirmed the presence of an antagonistic effect. The inflection points of cadmium and PFOS were determined to be −1.11 and 2.27, respectively. Additionally, exposure to cadmium and PFOS had the opposite effects on two crucial pathways, namely, the rap1 and calcium signaling pathways, which involve core genes related to depression such as ADORA2A, FGF2, and FGFR1. These findings have significant implications for future studies and provide new strategies for exploring the mechanisms underlying co-exposure effects.

Fragmentation of polypropylene into microplastics promoted by photo-aging; release of metals, toxicity and inhibition of biodegradability

The widespread presence of microplastics (MP) in water represents an environmental problem, not only because of the harmful effects of their size and potential to vector other pollutants, but also because of the release of additives, degradation products and residues contained in the polymer matrix. The latter includes metallic catalysts, which are often overlooked. This study focuses on the photo-aging of polypropylene (PP) and the resulting structural changes that promote its fragmentation microplastics (PP-MPs) and release of metals, as well as the resulting toxicity of leachates and their potential to inhibit biodegradation of organics in water. The pristine, photo-aged and waste PP are ground under the same regime to assess susceptibility to fragmentation. Obtained PP-MPs are submitted to leaching tests; the release of organics and metals is monitored by Total Organic Carbon (TOC) and Inductively Coupled Plasma Mass Spectrometry (ICP-MS) analysis, respectively. The leachates are assessed for their toxicity against Vibrio fischeri, Daphnia magna and Pseudokirchneriella subcapitata and their influence on the biodegradability of the glucose solution. Photo-aging induced changes in the crystallinity and morphology of the PP and manifested in the abundance of smaller MPs, as revealed by the particle size distribution. In the case of pristine PP, all particles were > 100 μm in size, while aged PP yielded significant mass fraction of MPs <100 μm. The toxicity of leachates from aged PP-MPs is higher than that of pristine and exhibits a positive correlation with portion of metals released. The biodegradability of glucose is strongly inhibited by PP-MPs leachates containing a mixture of metals in trace concentrations.

The Synthesis and Analysis of the Cytotoxicity of Al2O3-Supported Silver Nanoparticles Prepared by the Plasma Chemical Process Initiated by Pulsed MW Radiation in the Al2O3-Ag Powder Mixtures.

An original plasma chemical process initiated by microwave discharge in a mixture of metal and dielectric powders was applied to prepare specific materials, which consisted of microsized spherical particles of aluminum oxide covered with silver nanoparticles. The prepared materials are highly uniform in shape, size distribution, and composition. Their cytotoxicity was investigated using the human cell lines MCF7, HEK293T, A549, and VA-13 and the bacterial strains E. coli JW5503 (ΔtolC) and E. coli K12. Their cytotoxicity was found not to exceed the cytotoxicity of the starting materials. Thus, the prepared materials can be considered highly promising for catalysis and biotechnology applications.

APOE ε4 allele modifies the associations of toxic metals and their mixture with cognitive impairment among older adults

BackgroundThe evidence of interactive effect of the toxic metal (TM) mixture and apolipoprotein E (APOE) ε4 gene on cognitive impairment in older adults is scarce. We aimed to explore whether the associations of single TMs and their mixture with cognitive impairment depend on APOE ε4 in Chinese community-dwelling older people. MethodsA total of 1148 older adults from a subset of the baseline survey of a cohort study were included. Blood arsenic (As), cadmium (Cd), lead (Pb), strontium (Sr), and vanadium (V) were detected by inductively coupled plasma mass spectrometry. APOE gene (rs429358, rs7412) polymorphisms were analyzed by the Polymerase Chain Reaction instrument. Mixed effects logistic regression was applied to estimate the relationships of single TMs and APOE genotype with cognitive impairment. Weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models were performed to examine joint impacts of the TM mixture, as well as the interaction of the TM mixture with APOE ε4 genotype on cognitive impairment. ResultsPb displayed a significant linear association with an increased odds of cognitive impairment after adjustment for covariates (Ptrend = 0.045). While APOE genotype did not show a significant correlation with cognitive impairment. WQS showed that the TM mixture was associated with an increased risk of cognitive impairment by 31.0% (OR=1.31, 95% CI: 0.92, 1.87) while no significance was found. BKMR exhibited a significant linear association between the TM mixture and cognitive impairment. Moreover, both WQS and BKMR indicated that Pb contributed the most to cognitive impairment within the mixture. Significant interactions of Pb or the TM mixture and APOE genotype on cognitive impairment were observed, contributing to 38.1% and 38.2% of total effects, respectively. ConclusionsAPOE ε4 allele amplifies the associations of single Pb or the TM mixture with cognitive impairment. These findings may help to develop precision prevention.

Electro-Coloring Mechanism of Aluminum Anodic Oxides in Tin-Based Electrolytes

A method for accurately determining the chemical composition of deposits at the bottom of pores during the electrocoloring (e-coloring) of aluminum anodic oxide (AAO) layers in tin-based solutions is developed. The aluminum samples were AC e-colored after DC sulfuric anodization. Free-standing, tin e-colored aluminum oxide film was obtained by selective dissolution of the metallic aluminum from the AAO in copper chloride solution to access the deposit directly at the bottom of the pore. This allowed us to conduct XPS analysis directly on the deposits at pore bottoms without any interference from the base material or insulating barrier layer. The results revealed the presence of a mixture of tin oxide and metal in the deposits, which were richer in oxide content. Furthermore, a cyclic voltammetry experiment mimicking real polarization conditions during AC conditions was optimized and used to gain a deeper understanding of the electrochemical reactions that occur during AC electrocoloring. The comparison of CV results in tin-free and tin-containing electrolytes indicated that the tin deposited during a cathodic cycle is oxidized in the anodic cycle. The formation of tin-based deposits radically changed the CV behavior. The XPS and cyclic voltammetry results consistently show that the deposits formed during e-coloring comprised a mixture of metallic and oxidic tin species richer in oxide content.

Metal-silicate mixing in planetesimal collisions

Impacts between differentiated planetesimals are ubiquitous in protoplanetary discs and may mix materials from the core, mantle, and crust of planetesimals, thus forming stony-iron meteorites. The surface composition of the asteroid (16) Psyche represents a mixture of metal and non-metal components. However, the velocities, angles, and outcome regimes of impacts that mixed metal and silicate from different layers of planetesimals are debated. Our aim is to investigate the impacts between planetesimals that can mix large amounts of metal and silicate, and the mechanism of stony-iron meteorite formation. We used smooth particle hydrodynamics to simulate the impacts between differentiated planetesimals with various initial conditions that span different outcome regimes. In our simulations, the material strength was included and the effects of the states of planetesimal cores were studied. Using a statistical approach, we quantitatively analysed the distributions of metal and silicate after impacts. Our simulations modelled the mass, depth, and sources of the metal-silicate mixture in different impact conditions. Our results suggest that the molten cores in planetesimals could facilitate mixing of metal and silicate. Large amounts of the metal-silicate mixture could be produced by low-energy accretional impacts and high-energy erosive impacts in the largest impact remnant, and by hit-and-run and erosive impacts in the second-largest impact remnant. After impact, most of the metal-silicate mixture was buried at depth, consistent with the low cooling rates of stony-iron meteorites. Our results indicate that mesosiderites potentially formed in an erosive impact, while pallasites potentially formed in an accretional or hit-and-run impact. The mixing of metal and non-metal components on Psyche may also be the result of impacts.

Manganese and Vanadium Co-Exposure Induces Severe Neurotoxicity in the Olfactory System: Relevance to Metal-Induced Parkinsonism.

Chronic environmental exposure to toxic heavy metals, which often occurs as a mixture through occupational and industrial sources, has been implicated in various neurological disorders, including Parkinsonism. Vanadium pentoxide (V2O5) typically presents along with manganese (Mn), especially in welding rods and high-capacity batteries, including electric vehicle batteries; however, the neurotoxic effects of vanadium (V) and Mn co-exposure are largely unknown. In this study, we investigated the neurotoxic impact of MnCl2, V2O5, and MnCl2-V2O5 co-exposure in an animal model. C57BL/6 mice were intranasally administered either de-ionized water (vehicle), MnCl2 (252 µg) alone, V2O5 (182 µg) alone, or a mixture of MnCl2 (252 µg) and V2O5 (182 µg) three times a week for up to one month. Following exposure, we performed behavioral, neurochemical, and histological studies. Our results revealed dramatic decreases in olfactory bulb (OB) weight and levels of tyrosine hydroxylase, dopamine, and 3,4-dihydroxyphenylacetic acid in the treatment groups compared to the control group, with the Mn/V co-treatment group producing the most significant changes. Interestingly, increased levels of α-synuclein expression were observed in the substantia nigra (SN) of treated animals. Additionally, treatment groups exhibited locomotor deficits and olfactory dysfunction, with the co-treatment group producing the most severe deficits. The treatment groups exhibited increased levels of the oxidative stress marker 4-hydroxynonenal in the striatum and SN, as well as the upregulation of the pro-apoptotic protein PKCδ and accumulation of glomerular astroglia in the OB. The co-exposure of animals to Mn/V resulted in higher levels of these metals compared to other treatment groups. Taken together, our results suggest that co-exposure to Mn/V can adversely affect the olfactory and nigral systems. These results highlight the possible role of environmental metal mixtures in the etiology of Parkinsonism.

Implantable Wet‐Adhesive Flexible Electronics with Ultrathin Gelatin Film

AbstractImplantable flexible electronic has attracted significant research interest in various fields. However, it still faces the challenge of simultaneously achieving tight adhesion to tissues in a mildly wet environment and possessing excellent biocompatibility to reduce immune rejection reactions after implantation. Here, a degradable wet‐adhesive flexible electronic device based on liquid metal and ultrathin gelatin film is developed. The ultrathin gelatin film forms numerous hydrogen bonds with tissue in a slightly humid environment, rapidly constructing a wet‐adhesive interface without damaging tissue structure. Inkjet printing is utilized to pattern the mixture of liquid metal and PVP on the surface of the ultrathin gelatin to create flexible patch. With the excellent conductivity of liquid metal, low toxicity, and similarity to natural tissue components of gelatin, flexible patch exhibits outstanding biocompatibility and fatigue resistance. It can be implanted in the body for up to 6 weeks, retaining monitoring capabilities and resisting 1 000 000 cycles of bending fatigue. This study provides a novel strategy for the future development of implantable flexible electronics.

Complex interplay of heavy metals and renal injury: New perspectives from longitudinal epidemiological evidence

BackgroundEpidemiological studies have reported associations between heavy metals and renal function. However, longitudinal studies are required to further validate these associations and explore the interactive effects of heavy metals on renal function and their directional influence. MethodThis study, conducted in Northeast China from 2016 to 2021, included a four-time repeated measures design involving 384 participants (1536 observations). Urinary concentrations of chromium (Cr), cadmium (Cd), manganese (Mn), and lead (Pb) were measured, along with renal biomarkers including urinary microalbumin (umAlb), urinary albumin-to-creatinine ratio (UACR), N-acetyl-β-D-glucosaminidase (NAG), and β2-microglobulin (β2-MG) levels. Estimated glomerular filtration rate (eGFR) was calculated. A Linear Mixed Effects Model (LME) examined the association between individual metal exposure and renal biomarkers. Subsequently, Quantile g-computation and Bayesian Kernel Machine Regression (BKMR) models assessed the overall effects of heavy metal mixtures. Marginal Effect models examined the directional impact of metal interactions in the BKMR on renal function. ResultResults indicate significant impacts of individual and combined exposures of Cr, Cd, Pb, and Mn on renal biomarkers. Metal interactions in the BKMR model were observed, with synergistic effects of Cd-Cr on NAG, umAlb, UACR; Cd-Pb on NAG, UACR; Pb-Cr on umAlb, UACR, eGFR-MDRD, eGFR-EPI; and an antagonistic effect of Mn-Pb-Cr on UACR. ConclusionBoth individual and combined exposures to heavy metals are associated with renal biomarkers, with significant synergistic interactions leading to renal damage. Our findings elucidate potential interactions among these metals, offering valuable insights into the mechanisms linking multiple metal exposures to renal injury.

Advancing Simultaneous Extraction and Sequential Single-Particle ICP-MS Analysis for Metallic Nanoparticle Mixtures in Plant Tissues.

Engineered nanoparticles (ENPs) have been increasingly used in agricultural operations, leading to an urgent need for robust methods to analyze co-occurring ENPs in plant tissues. In response, this study advanced the simultaneous extraction of coexisting silver, cerium oxide, and copper oxide ENPs in lettuce shoots and roots using macerozyme R-10 and analyzed them by single-particle inductively coupled plasma-mass spectrometry (ICP-MS). Additionally, the standard stock suspensions of the ENPs were stabilized with citrate, and the long-term stability (up to 5 months) was examined for the first time. The method performance results displayed satisfactory accuracies and precisions and achieved low particle concentration and particle size detection limits. Significantly, the oven drying process was proved not to impact the properties of the ENPs; therefore, oven-dried lettuce tissues were used in this study, which markedly expanded the applicability of this method. This robust methodology provides a timely approach to characterize and quantify multiple coexisting ENPs in plants.

Metal Toxicity: Effects on Energy Metabolism in Fish.

Metals are dispersed in natural environments, particularly in the aquatic environment, and accumulate, causing adverse effects on aquatic life. Moreover, chronic polymetallic water pollution is a common problem, and the biological effects of exposure to complex mixtures of metals are the most difficult to interpret. In this review, metal toxicity is examined with a focus on its impact on energy metabolism. Mechanisms regulating adenosine triphosphate (ATP) production and reactive oxygen species (ROS) emission are considered in their dual roles in the development of cytotoxicity and cytoprotection, and mitochondria may become target organelles of metal toxicity when the transmembrane potential is reduced below its phosphorylation level. One of the main consequences of metal toxicity is additional energy costs, and the metabolic load can lead to the disruption of oxidative metabolism and enhanced anaerobiosis.

Association of Blood Copper With the Subclinical Carotid Atherosclerosis: An Observational Study.

Copper exposure is reported to be associated with increased risk of stroke. However, the association of copper exposure with subclinical carotid atherosclerosis remains unclear. This observational study included consecutive participants from Xinqiao Hospital between May 2020 and August 2021. Blood metals were measured using inductively coupled plasma mass spectrometry and carotid atherosclerosis was assessed using ultrasound. Modified Poisson regression was performed to evaluate the associations of copper and other metals with subclinical carotid plaque presence. Blood metals were analyzed as categorical according to the quartiles. Multivariable models were adjusted for age, sex, body mass index, education, smoking, drinking, hypertension, diabetes, dyslipidemia, estimated glomerular filtration rate, and coronary artery disease history. Bayesian Kernel Machine Regression was conducted to evaluate the overall association of metal mixture with subclinical carotid plaque presence. One thousand five hundred eighty-five participants were finally enrolled in our study, and carotid plaque was found in 1091 subjects. After adjusting for potential confounders, metal-progressively-adjusted models showed that blood copper was positively associated with subclinical carotid plaque (relative risk according to comparing quartile 4 to quartile 1 was 1.124 [1.021-1.238], relative risk according to per interquartile increment was 1.039 [1.008-1.071]). Blood cadmium and lead were also significantly associated with subclinical carotid plaque. Bayesian Kernel Machine Regression analyses suggested a synergistic effect of copper-cadmium-lead mixture on subclinical carotid plaque presence. Our findings identify copper as a novel risk factor of subclinical carotid atherosclerosis and show the potential synergistic proatherogenic effect of copper, cadmium, and lead mixture.

Metal mixture exposures and serum lipid levels in childhood: the Rhea mother-child cohort in Greece.

Growing evidence suggests that cardiovascular disease develops over the lifetime, often beginning in childhood. Metal exposures have been associated with cardiovascular disease and important risk factors, including dyslipidemia, but prior studies have largely focused on adult populations and single metal exposures. To investigate the individual and joint impacts of multiple metal exposures on lipid levels during childhood. This cross-sectional study included 291 4-year-old children from the Rhea Cohort Study in Heraklion, Greece. Seven metals (manganese, cobalt, selenium, molybdenum, cadmium, mercury, and lead) were measured in whole blood using inductively coupled plasma mass spectrometry. Serum lipid levels included total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol. To determine the joint and individual impacts of child metal exposures (log2-transformed) on lipid levels, Bayesian kernel machine regression (BKMR) was employed as the primary multi-pollutant approach. Potential effect modification by child sex and childhood environmental tobacco smoke exposure was also evaluated. BKMR identified a positive association between the metal mixture and both total and LDL cholesterol. Of the seven metals examined, selenium (median 90.6 [IQR = 83.6, 96.5] µg/L) was assigned the highest posterior inclusion probability for both total and LDL cholesterol. A difference in LDL cholesterol of 8.22 mg/dL (95% CI = 1.85, 14.59) was observed when blood selenium was set to its 75th versus 25th percentile, holding all other metals at their median values. In stratified analyses, the positive association between selenium and LDL cholesterol was only observed among boys or among children exposed to environmental tobacco smoke during childhood. Growing evidence indicates that cardiovascular events in adulthood are the consequence of the lifelong atherosclerotic process that begins in childhood. Therefore, public health interventions targeting childhood cardiovascular risk factors may have a particularly profound impact on reducing the burden of cardiovascular disease. Although growing evidence supports that both essential and nonessential metals contribute to cardiovascular disease and risk factors, such as dyslipidemia, prior studies have mainly focused on single metal exposures in adult populations. To address this research gap, the current study investigated the joint impacts of multiple metal exposures on lipid concentrations in early childhood.

Ciprofloxacin Metal Complexes–Silica Nanoparticles: Characterization, Spectroscopic Study, DNA Interaction and Biological Activity

Ciprofloxacin (CIPH) was classified as one of the most effective quinolone antibiotics, which is commonly used to cure a wide range of infections resulting from Gram-negative and Gram-positive microorganisms. The complexes which formed due to the interaction of Ni(II), Zn(II), Cu(II), Gd(III) and Sm(III) with ciprofloxacin were characterized by CHN% analysis, conductivity, FTIR, electronic spectra, fluorescence measurements, and magnetic susceptibility, besides studying the complex–DNA interaction. Meanwhile, the molar conductance values (0.001 mol·L−1 in DMSO) revealed the electrolytic behavior of the complexes and could be designated with the A−B+ formula. In addition, the geometry of the compounds was confirmed from the electronic transitions as well as the μeff values as octahedral for all complexes. The postulated formula could be generally assigned as [M(CIP)a(CIPH)b(H2O)c](NO3)(H2O)n(C2H5OH)m. Moreover, the interaction between metal complexes and DNA revealed that the Cu complex had the highest binding constant. Nanotechnology was applied to synthesized compounds using silica nanoparticles (SiNPs), which were prepared using a sol–gel process. The silica nanoparticles were chemically functionalized for binding the ligand and its metal complexes; this enables the as-prepared compounds to enhance their features as a drug delivery platform. Meanwhile, the antimicrobial activity was tested for the free complexes and SiNPs composites. Collectively, Sm complex gave the largest zone of inhibition, while the Cu(II)–SiNPs composite showed the strongest potential to reduce the bacterial activity. Furthermore, the fluorescence data of CIPH, ligand–metal mixture and the effect of silica nanoparticles on them were studied.

Thyroid under siege: Unravelling the toxic impact of real-life metal mixture exposures in Wistar rats

This study explored the effect of a toxic metal(oid) mixture (cadmium, lead, arsenic, mercury, chromium, and nickel) on thyroid function in Wistar rats exposed for 28 or 90 days. Dose levels were determined based on prior human-biomonitoring investigation. The experiment included control (male/female rats, 28 and 90 days) and treated groups, reflecting the lower confidence limit of the Benchmark Dose (BMDL) for hormone levels (M1/F1, 28 and 90 days), median concentrations (M2/F2, 28 and 90 days), 95th percentile concentrations (M3/F3, 28 and 90 days) measured in a human study, and reference values for individual metals extracted from the literature (M4/F4, 28 days only). Blood and thyroid gland samples were collected at the experimental termination. Serum TSH, fT3, fT4, T3, and T4 levels were measured, and SPINA-GT and SPINA-GD parameters were calculated. In silico analysis, employing the Comparative Toxicogenomic Database and ToppGene Suite portal, aimed to reveal molecular mechanisms underlying the observed effects. Results showed greater sensitivity in the female rats, with significant effects observed at lower doses. Subacute exposure increased TSH, fT3, and T3 levels in females, while subchronic exposure in males decreased TSH and fT3 levels and increased fT4. Subacute exposure induced changes even at allegedly safe doses, emphasizing potential health risks. Histological abnormalities were observed in all the treated groups. In silico findings suggested that toxic metal exposure contributes to thyroid disorders via oxidative stress, disruption of micronutrients, interference with hormone synthesis, and gene expression dysregulation. These results indicate that seemingly safe doses in single-substance research can adversely affect thyroid structure and function when administered as a mixture. These findings highlight the complex impact of toxic metal exposure on thyroid health, emphasizing that adhering to accepted safety limits for single-substance research fails to account for adverse effects on thyroid structure and function upon exposures to metal mixtures.

Associations between prenatal metal and metalloid mixtures in teeth and reductions in childhood lung function

BackgroundMetal(oid)s have been cross-sectionally associated with lung function outcomes in childhood but there is limited data on their combined effects starting in utero. Child sex may further modify these effects. ObjectiveExamine associations between in utero and early life exposure to metals assessed via novel dentine biomarkers and childhood lung function and explore effect modification by child sex. MethodsAnalyses included 291 children enrolled in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study, a longitudinal birth cohort study in Mexico City. Weekly dentine levels of arsenic (As), cadmium (Cd), cobalt (Co), copper (Cu), manganese (Mn), nickel (Ni), and lead (Pb) were measured from 15 weeks pre-birth to 15 weeks post birth in deciduous children's teeth. Lung function was tested at ages 8–14 years and then modeled as age, height and sex adjusted z-scores. Associations were modeled using lagged weighted quantile sum (LWQS) regression to evaluate the potential for a time-varying mixture effect adjusting for maternal age and education at enrollment and exposure to environmental tobacco smoke in pregnancy. Models were also stratified by sex. ResultsWe identified a window of susceptibility at 12–15 weeks pre-birth in which the metal mixture was associated with lower FVC z-scores in children aged 8–14 years. Cd and Mn were the largest contributors to the mixture effect (70 %). There was also some evidence of effect modification by sex, in which the mean weights and weighted correlations over the identified window was more evident in males when compared to females. In the male stratum, Cd, Mn and additionally Pb also dominated the mixture association. ConclusionsPrenatal metal(oid) exposure was associated with lower lung function in childhood. These findings underscore the need to consider both mixtures and windows of susceptibility to fully elucidate effects of prenatal metal(oid) exposure on childhood lung function.

Comparative mathematical modeling of causal association between metal exposure and development of chronic kidney disease.

Previous studies have identified several genetic and environmental risk factors for chronic kidney disease (CKD). However, little is known about the relationship between serum metals and CKD risk. We investigated associations between serum metals levels and CKD risk among 100 medical examiners and 443 CKD patients in the medical center of the First Hospital Affiliated to China Medical University. Serum metal concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS). We analyzed factors influencing CKD, including abnormalities in Creatine and Cystatin C, using univariate and multiple analysis such as Lasso and Logistic regression. Metal levels among CKD patients at different stages were also explored. The study utilized machine learning and Bayesian Kernel Machine Regression (BKMR) to assess associations and predict CKD risk based on serum metals. A chained mediation model was applied to investigate how interventions with different heavy metals influence renal function indicators (creatinine and cystatin C) and their impact on diagnosing and treating renal impairment. Serum potassium (K), sodium (Na), and calcium (Ca) showed positive trends with CKD, while selenium (Se) and molybdenum (Mo) showed negative trends. Metal mixtures had a significant negative effect on CKD when concentrations were all from 30th to 45th percentiles compared to the median, but the opposite was observed for the 55th to 60th percentiles. For example, a change in serum K concentration from the 25th to the 75th percentile was associated with a significant increase in CKD risk of 5.15(1.77,8.53), 13.62(8.91,18.33) and 31.81(14.03,49.58) when other metals were fixed at the 25th, 50th and 75th percentiles, respectively. Cumulative metal exposures, especially double-exposure to serum K and Se may impact CKD risk. Machine learning methods validated the external relevance of the metal factors. Our study highlights the importance of employing diverse methodologies to evaluate health effects of metal mixtures.