Mitigation of thallium threat in paddy soil and rice plant by application of functional biochar.

Thallium (Tl) is a highly toxic metal, and its contamination in soils entails high risks to human health via food chain. It remains largely unknown of the effects of applying biochar on Tl uptake in paddy systems despite that few studies have shown that biochar exhibits great potential for decreasing Tl bioavailability in soils. Herein, we examined the mitigating effects of the application of biochar (5 and 20 g/kg pristine biochar; 5 and 20 g/kg Fe/Mn-modified biochar) on Tl uptake in paddy soil and rice plant after an entire rice growth period. The results suggested that the application of Fe/Mn-modified biochar (FMBC) considerably mitigated the accumulation of Tl in different tissues of rice plants. Specifically, total Tl content in rice plants treated with FMBC-20 decreased by over 75% compared with control experiment. In addition, the amendment of FMBC in Tl-rich paddy soils can enhance the communities of microorganisms (Actinobacteria and Proteobacteria). Further analysis of the soil microbial symbiosis network revealed that FMBC promotes the living microorganisms to play modular synergistic interactions, which is crucial for FMBC-induced Tl stabilization in soils. All these findings indicated that FMBC is an efficient and environmentally friendly Tl-immobilization alternative material and can be potentially used in the remediation of Tl-contaminated paddy soils and/or cropland.

Assessment of toxic effects of thallium on the earthworm Eisenia fetida using the biomarker response index.

Thallium (Tl), though not essential for biological systems, is widely used in industrial activities, resulting in soil pollution and adverse effects on soil biota. Systematic toxicological studies on Tl, especially concerning soil organisms, are relatively rare. This research evaluates the toxic effects of Tl on earthworms by measuring oxidative stress biomarkers, such as superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG), and by assessing the expression of functional genes, such as heat shock protein 70 (Hsp70), metallothionein (MT), and annetocin (ANN). Additionally, this study employs the Biomarker Response Index (BRI) and two-way ANOVA to comprehensively assess the cumulative toxicity of Tl in earthworms. The findings indicate that Tl exposure significantly exacerbates oxidative stress and cellular damage in earthworms, particularly under conditions of high concentration and prolonged exposure. BRI results demonstrate a continuous decline in the physiological state of earthworms with increasing Tl concentration and exposure duration. Two-way ANOVA reveals significant dose-responsive increases in SOD and CAT activities, as well as in ANN gene expression. Apart from GST activity, other biomarkers significantly increased over time, and the changes in biomarkers such as SOD, CAT, MDA, and 8-OHdG were significantly influenced by dose and time. LSD post hoc tests show significant effects of dose, time, and their interactions on all biomarkers except for GST. These findings are valuable for gaining a deeper understanding of the ecological risks of Tl in soil environments and its potential threats to soil biota, aiding in the management of ecological risks associated with Tl-contaminated soils.

Ecotoxicity of thallium to two soil animal species with different niches and modification by organic materials.

Soil thallium (Tl) contamination is of major public concern but little is known about soil Tl ecological toxicity or potential ecological remediation strategies. Here, two soil animal species with different ecological niches, Folsomia candida and Enchytraeus crypticus, were used to test Tl toxicity and modification by exogenous organic materials (i.e. maize straw and biochar). The endpoints of Tl ecotoxicity to F. candida and E. crypticus were studied at two biological levels, i.e., the individual (body Tl concentrations) and the population (survival, reproduction, and growth). Thallium concentrations in F. candida and E. crypticus increased with increasing soil Tl concentration, and their survival and reproduction rates decreased with increasing soil Tl concentration. The LC50 value of Tl effects on F. candida mortality (28 d) was 24.0 mg kg-1 and the EC50 value of reproduction inhibition was 6.51 mg kg-1. The corresponding values were 4.15 mg kg-1 and 2.31 mg kg-1 respectively for E. crypticus showing higher sensitivity to soil Tl than F. candida. These effective values are comparable to or much lower than the environmental Tl concentrations in field soils, suggesting high potential ecological risk. Both biochar and straw can decrease animal body Tl concentrations in different ways, i.e. reducing Tl availability or offering clean food sources, and addition of exogenous organic materials clearly mitigated Tl ecotoxicity in highly polluted soil. The results highlight the potential Tl ecological risk to soil animals and the potential use of organic materials to control the toxicity.

Thallium spill shifts the structural and functional characteristics of viral communities with different lifestyles in river sediments.

Thallium (Tl), a highly toxic heavy metal, can affect microbial community, while little is known about its effect on viral community. The present study investigated the variation of viral communities, as well as their interactions with microbial hosts under Tl stress. Tl in sediments significantly altered the composition and diversity of the viral communities, but showed no significant links with the prokaryotic communities, which may reveal a potential discrepancy in the sensitivity of the viral and prokaryotic communities to heavy metal stress. Auxiliary metabolic genes (AMGs) involved in denitrification, methane oxidation and organic sulfur transformation were enriched at T1-contaminated sites, while the abundance of AMGs related to methanogenesis and sulfate reduction were higher at pristine sites. Specially, the enrichment of AMGs involved in assimilatory sulfate reduction in Tl-contaminated sites could possibly reduce Tl bioavailability by enhancing the microbially-driven sulfur cycling to generate sulfides that could be complexed with Tl. Moreover, there was a significantly positive correlation between virus-carrying metal resistant genes and the sedimentary Tl concentration, implying that Tl contamination might enhance the metal resistant potential of the viruses. Serving as the functional gene reservoir, the response of viral AMGs to Tl stress could represent a potential pathway for microorganisms to be adapted to the metal-polluted environments. Our study provided novel insights into the impact of Tl spill on viral communities, shedding light on functional characteristics and the links of virus-host interaction with Tl level.

Heavy metal concentrations and clinical symptoms in patients diagnosed with schizophrenia related to cigarette smoking.

In our study, blood concentrations of lead (Pb), arsenic (As), and cadmium (Cd) and urine concentrations of thallium (Tl) were measured together with related symptoms of heavy metal poisoning in cigarette smoking volunteers diagnosed with schizophrenia, in cigarette smokers not diagnosed with schizophrenia, and in the control group of non-smokers and not diagnosed with schizophrenia volunteers. Our study was performed on 171 volunteers divided into the following subgroups: patients diagnosed with schizophrenia with at least 1 year of continuous cigarette smoking experience (56 participants), cigarette smokers not diagnosed with schizophrenia with at least one year of continuous smoking experience (58), and control group (not diagnosed with schizophrenia and non-smoking volunteers) (57). Smoking durations of cigarette smokers diagnosed with schizophrenia and cigarette smokers not diagnosed with schizophrenia are not similar (p = 0.431). Blood Pb, As, and Cd concentrations and urine Tl concentrations were the highest in the subgroup of cigarette smokers not diagnosed with schizophrenia, followed by the subgroup of cigarette smokers diagnosed with schizophrenia, and the control group. Only blood Pb concentrations were significantly higher (probability value p < 0.05) in the group of cigarette smokers not diagnosed with schizophrenia (5.16 µg/dL), comparing to the group of cigarette smokers diagnosed with schizophrenia (3.83 µg/dL) and to the control group (3.43 µg/dL). Blood Cd and As concentrations and urine Tl concentrations were significantly higher (p < 0.05) in cigarette smokers not diagnosed with schizophrenia than in the control group. The results revealed a statistically significant positive correlation (p < 0.001) in the cigarette smokers in the schizophrenia diagnosed group between blood Pb, blood As, and urine Tl concentrations and the duration of cigarette smoking.

Prenatal exposure to metal mixtures, body mass index trajectories in early life and effect modifiers: Insights from a prospective birth cohort study.

Current scientific knowledge is insufficient on the effects of metal mixtures on early life growth trajectories. This study included 7118 mother-infant pairs from a Chinese birth cohort. Concentrations of 18 maternal urinary metals were quantified, and growth trajectories were conducted based on standardized body mass index (BMI) for up to eight times from 0 to 2 years. A three-phase analytical framework was applied to explore the risk ratios (RR) and 95 % confidence intervals (95 % CI) of co-exposure to metals on dynamic growth, along with potential modifiers. Five growth trajectory groups were identified. Exposure to metal mixtures driven by thallium (Tl, 34.8 %) and aluminum (Al, 16.2 %) was associated with an increased risk of low-rising trajectory (RR=1.58, 95 % CI: 1.25, 2.00); however, exposure to mixtures driven by strontium (Sr, 49.5 %) exhibited an inverse correlation (RR = 0.81, 95 % CI: 0.67, 0.97). Furthermore, infants with varying levels of Tl, Al and Sr, as well as modifiers including pre-pregnancy BMI and infant sex faced distinct risks of low-rising trajectory. Our findings highlighted the Tl, Al, and Sr as key metals in relation to the low-rising trajectory in early life characterized as catch-up growth, with pre-pregnancy BMI and infant sex exerting as potential modifiers.

Fabrication of cobalt-iron Prussian blue analogues functionalized hybrid membranes for efficiently capturing Tl from water: Performance and mechanism.

As trace levels of thallium (Tl) in water are lethal to humans and ecosystems, it is essential to exploit advanced technologies for efficient Tl removal. In response to this concern, an innovative composite membrane was developed, incorporating polytetrafluoroethylene (PTFE) and featuring a dual-support system with polydopamine (PDA) and polyethyleneimine (PEI), along with bimetallic Prussian blue analogues (Co@Fe-PBAs) as co-supports. The composite membrane exhibited an exceptional Tl+-adsorption capacity (qm) of 186.1 mg g-1 when utilized for the treatment of water containing low concentration of Tl+ (0.5 mg⋅L-1). Transmission electron microscopy displayed the obvious Tl+ mapping inside the special hollow Co@Fe-PBAs crystals, demonstrating the deep intercalation of Tl+ via ion exchange and diffusion. The Tl+-adsorption capability of the composite membrane was not greatly affected by coexisting Na+, Ca2+ and Mg2+ as well as the tricky K+, indicating the excellent anti-interference. Co-doped PBAs enhanced ion exchange and intercalation of the composite membrane with Tl+ leading to excellent Tl+ removal efficiency. The composite membrane could efficiently remove Tl+ from thallium-contaminated river water to meet the USEPA standard. This study provides a cost-effective membrane-based solution for efficient Tl+ removal from Tl+-containing wastewater.

Potential of Castanea sativa for biomonitoring As, Hg, Pb, and Tl: A focus on their distribution in plant tissues from a former mining district.

Bioavailability of potentially toxic elements (PTEs) from the Earth's crust in the soil, e.g., As, Hg, Tl, and Pb, can pose a potential environmental and health risk because of human activities, especially related to mining extraction. The biomonitoring allows to detect PTE contamination through their measurement in living organisms as trees. However, the choice of which plant species and tissue to analyse is a key point to be evaluated in relation to PTE absorption and translocation. The aim of this work was to assess the As, Hg, Tl, and Pb distribution in Castanea sativa Mill. plant tissues, given its importance for both biomass and food production. The study identified two sites in the Alpi Apuane (Italy), with similar environmental conditions (e.g., elevation, exposure, forest type, and tree species) but different soil PTE levels. The topsoil was characterized, and the PTE fractions with different bioavailability were measured. The PTE concentrations were also analysed in chestnut plant tissues (leaves, bark, wood, nuts, and shells) in parallel with and evaluation of plant health status through the determination of micro and macronutrient concentrations and the leaf C and N isotope composition (δ13C or δ15N). Chestnut trees showed a good health status highlighting its suitability for Tl, As, Hg, and Pb biomonitoring, displaying a tissue-specific PTE allocation. Thallium and Hg were detected in all plant tissues at similar concentrations, As was found in leaves, wood, and nuts while Pb only in the bark. The δ15N negatively correlated with leaf Mn and Tl concentrations, suggesting possible changes in N source and/or plant metabolism due to the high contamination level and acid soil pH. Thallium in La Culla site trees was associated with its presence in the carbonate rocks but not in the topsoil, highlighting the potentiality of chestnut in providing valuable information for geochemical surveying.

Integration of beta counting system with ORION-DSP coupled to NaI(Tl) detector-a comparative study with an HPGe detector.

The integration of the ORION digital signal processing-based MCA system coupled with a 3″ × 3″ NaI(Tl) detector assembly with a GM detector for counting beta (ß) has eliminated the need for a standalone ß-γ method in which U3O8 is determined by gross ß and gross γ counting. Uraniferous and mixed U-Th samples were taken up for study and compared with the results obtained from Canberra p-type coaxial high resolution gamma ray spectrometry detector. In uraniferous samples, U3O8 values obtained are within ±10%, whereas in the case of mixed U-Th samples, U3O8 values are within ±15%. Regression graphs drawn between the outcomes from the two analytical systems indicate R2 > 0.95 for Ra(eU3O8) and ThO2. In uraniferous samples, the R2 value for U3O8 was found to be > 0.99, but in mixed U-Th samples, it is 0.92. The closeness of agreement between the results obtained from two methods at various concentrations over the analytical range shows that the integrated system is suitable for the quantitative determination of eU3O8, U3O8, Ra(eU3O8), ThO2 and K in geological rock samples.

Onset of coupled atmosphere-ocean oxygenation 2.3 billion years ago.

The initial rise of molecular oxygen (O2) shortly after the Archaean-Proterozoic transition 2.5 billion years ago was more complex than the single step-change once envisioned. Sulfur mass-independent fractionation records suggest that the rise of atmospheric O2 was oscillatory, with multiple returns to an anoxic state until perhaps 2.2 billion years ago1-3. Yet few constraints exist for contemporaneous marine oxygenation dynamics, precluding a holistic understanding of planetary oxygenation. Here we report thallium (Tl) isotope ratio and redox-sensitive element data for marine shales from the Transvaal Supergroup, South Africa. Synchronous with sulfur isotope evidence of atmospheric oxygenation in the same shales3, we found lower authigenic 205Tl/203Tl ratios indicative of widespread manganese oxide burial on an oxygenated seafloor and higher redox-sensitive element abundances consistent with expanded oxygenated waters. Both signatures disappear when the sulfur isotope data indicate a brief return to an anoxic atmospheric state. Our data connect recently identified atmospheric O2 dynamics on early Earth with the marine realm, marking an important turning point in Earth's redox history away from heterogeneous and highly localized 'oasis'-style oxygenation.

The potential of Actinoplanes spp. for alleviating the oxidative stress induced by thallium toxicity in wheat plants.

To reduce heavy metal toxicity, like that induced by thallium (TI) in plants, growth-promoting bacteria (GPB) are a widely used to enhance plant tolerance to heavy metals toxicity. In our study, we characterized seven GPB and identified Actinoplanes spp., as the most active strain. This bioactive strain was then applied to alleviate TI phytotoxicity. TI contamination (20 mg/kg soil) induced TI bioaccumulation, reducing wheat growth (biomass accumulation) and photosynthesis rate, by about 55% and 90%, respectively. TI stress also induced oxidative damages as indicated by increased oxidative markers (H2O2 and lipid peroxidation (MDA)). Interestingly, Actinoplanes spp. significantly reduced growth inhibition and oxidative stress by 20% and 70%, respectively. As a defense mechanism to mitigate the TI toxicity, wheat plants showed improved antioxidant and detoxification defense including increased phenolic and tocopherols levels as well as peroxidase (POX), catalase (CAT), superoxide dismutase (SOD), and glutathione reductase (GR) enzymes activities. These defense mechanisms were further induced by Actinoplanes spp. Additionally, Actinoplanes spp. increased the production of heavy metal-binding ligands such as metallothionein, phytochelatins, total glutathione, and glutathione S-transferase activity by 100%, 90%, 120%, and 100%, respectively. This study, therefore, elucidated the physiological and biochemical bases underlying TI-stress mitigation impact of Actinoplanes spp. Overall, Actinoplanes spp. holds promise as a valuable approach for ameliorating TI toxicity in plants. KEYBOARD: Actinobacteria, Bioaccumulation, Detoxification, Membrane damage, Redox regulation.

Amphichdiral enhancement on singlet oxygen generation and stable thallium immobilization using iron-driven copper oxide.

Thallium (Tl) as a prominent priority contaminant in aquatic environment necessitates rigorous regulation. However, limited horizon devotes the impact of selective oxidation on the process of thallium purification. In this study, selective active radical of singlet oxygen (1O2) was continually generated for Tl(Ⅰ) oxidation accomplished with efficient Tl(Ⅲ) immobilization using iron-driven copper oxide (CuFe)/peroxymonosulfate (PMS). Fe-doping changed the active center of electronic structure for enhancing the catalytic and adsorptive reactivities, and installed magnetism for solid-liquid separation. Rapid reaction rate (0.253 min-1) coupled with vigorous elimination efficiency (98.32%) relied on electrostatic attraction, surface complexation, and H-bond interaction. EPR and XPS analyses demonstrated that the synergistic effects of ≡ Cu(Ⅰ)/≡Cu(Ⅱ) and ≡ Fe(Ⅲ)/≡Fe(Ⅱ) redounded to the sustained generation of 1O2 through the pathway of PMS → •O2- → 1O2, and 1O2 exploited an advantage to selectively oxidize Tl(Ⅰ) to Tl(Ⅲ). 3D isosurface cubic charts revealed that the immobilizing ability of Tl(Ⅲ) hydrate for CuFe was notably superior to that of Tl(Ⅲ) hydrate for CuO and Tl(Ⅰ) hydrate for CuO/CuFe, which further attested surface reactivity promoted stable immobilization form. This work develops the continuous generation of 1O2 and stable immobilization with the goal of efficiently cleansing Tl-containing wastewater.

Thallium in Technosols from Allchar (North Macedonia): Isotopic and speciation insights.

Allchar (North Macedonia) mining area is known for anomalous background Tl concentrations. In this study, we combine accurate detection of Tl stable isotope ratios with data on mineralogy/speciation and chemical extraction of Tl in Tl-contaminated Technosol profiles. We demonstrate that Tl in the studied soils varies significantly in both concentration (500 mg/kg-18 g/kg) and isotopic composition (-1.6 and +3.2 of ε205Tl, a ∼0.5‰ spread), which is due to changes in the phase chemistry and/or mineralogy of Tl. Moreover, the observed 205Tl/203Tl ratios do not reflect the extent to which individual soils undergo Tl isotopic fractionation during mineral weathering and soil formation. Clearly, they reflect the initial isotopic signal(s) of the primary ore or ore minerals, and thus, the general history or type of their genesis. As the Tl carriers, various types of Tl-Me-arsenates, mixtures of jarosite and dorallcharite and minor Mn-oxides predominated. We revealed intense adsorption of Tl by the identified Mn-oxides (≤6.7 at.%). It is hypothesized that these phases are of key importance in the fractionation of Tl isotopes, meaning at this type of secondary oxide-soil solution interface. However, model studies involving primary/secondary components (sulfides, sulfates, oxides and arsenates) are required to understand the mechanisms that may lead to post-depositional Tl isotopic redistribution in soils, as well as Tl isotope systematics in mining wastes in general.

Cell-Based Thallium-Influx Fluorescence Assay for Kv10.1 Channels.

The development of cell-based fluorescent assays has resulted in an incredible tool for searching new ion channels' modulators with a biophysical and clinical profile. Among all the ion channels, potassium (K+)-permeable channels represent the most diverse and relevant for cell function, making them attractive targets for drug discovery. Some of the cell-based assays for K+ channels take advantage of a thallium-sensitive dye whose fluorescence increased upon the binding of thallium (Tl+), an ion able to move through K+ channels. We optimize the FLIPR Potassium Assay Kit based on thallium influx to measure the Kv10.1 activity.

The Impact of Thallium Exposure in Public Health and Molecular Toxicology: A Comprehensive Review.

This review offers a synthesis of the current understanding of the impact of low-dose thallium (Tl) on public health, specifically emphasizing its diverse effects on various populations and organs. The article integrates insights into the cytotoxic effects, genotoxic potential, and molecular mechanisms of thallium in mammalian cells. Thallium, a non-essential heavy metal present in up to 89 different minerals, has garnered attention due to its adverse effects on human health. As technology and metallurgical industries advance, various forms of thallium, including dust, vapor, and wastewater, can contaminate the environment, extending to the surrounding air, water sources, and soil. Moreover, the metal has been identified in beverages, tobacco, and vegetables, highlighting its pervasive presence in a wide array of food sources. Epidemiological findings underscore associations between thallium exposure and critical health aspects such as kidney function, pregnancy outcomes, smoking-related implications, and potential links to autism spectrum disorder. Thallium primarily exerts cellular toxicity on various tissues through mitochondria-mediated oxidative stress and endoplasmic reticulum stress. This synthesis aims to shed light on the intricate web of thallium exposure and its potential implications for public health, emphasizing the need for vigilant consideration of its risks.

The determination of thallium in the environment: A review of conventional and advanced techniques and applications.

Thallium (Tl) is a potential toxicity element that poses significant ecological and environmental risks. Recently, a substantial amount of Tl has been released into the environment through natural and human activities, which attracts increasing attention. The determination of this hazardous and trace element is crucial for controlling its pollution. This article summarizes the advancement and progress in optimizing Tl detection techniques, including atomic absorption spectroscopy (AAS), voltammetry, inductively coupled plasma (ICP)-based methods, spectrophotometry, and X-ray-based methods. Additionally, it introduces sampling and pretreatment methods such as diffusive gradients in thin films (DGT), liquid-liquid extraction, solid phase extraction, and cloud point extraction. Among these techniques, ICP-mass spectrometry (MS) is the preferred choice for Tl detection due to its high precision in determining Tl as well as its species and isotopic composition. Meanwhile, some new materials and agents are employed in detection. The application of novel work electrode materials and chromogenic agents is discussed. Emphasis is placed on reducing solvent consumption and utilizing pretreatment techniques such as ultrasound-assisted processes and functionalized magnetic particles. Most detection is performed in aqueous matrices, while X-ray-based methods applied to solid phases are summarized which provide non-destructive analysis. This work improves the understanding of Tl determination technology while serving as a valuable resource for researchers seeking appropriate analytical techniques.

ION Thallos-HTL: a fluorescent thallium indicator that enables cell-selective and localizable thallium flux assays.

Ion channels are essential proteins for all organisms. Electrophysiology is a useful and commonly employed method to study ion channels, however there is a need for operationally simpler, cost-effective and higher throughput techniques to study ion channel functions in their native environments. Fluorescent ion indicators, such as Fluo-4 and Thallos, have been used for decades to study ion channel activity by measuring the flux of ions through channels of interest. In this work, we present ION Thallos-HTL, a thallium indicator that can be localized using HaloTag technology. This novel indicator enables specific labeling of cells and intracellular compartments in live cells and responds to changes in thallium concentration within these environments. We demonstrate the utility of ION Thallos-HTL by conducting a thallium flux assay using high-throughput instrumentation in a mixed cell population where some cells are expressing HaloTag and some are not.

Investigation of thallium as a contaminant in dietary supplements marketed for weight loss and physical fitness.

Dietary supplements are drastically growing as a category of consumer products all over the world. The abuse of supplements marketed for slimming purposes and physical fitness has been observed worldwide in recent years, which raises concerns in terms of public health. In this study, different types of dietary supplements marketed and delivered through the e-commerce were studied for the determination of thallium as a hazardous inorganic contaminant. The total content of thallium was determined by a sensitive voltammetric method after a microwave-assisted oxidative digestion of the sample. In addition, a comparative spectrometric method was applied for validation of the results in the samples. The maximum concentration found for thallium was found to be 2.89 mg kg-1, which well agree with the comparative measurement. Considering the 32 studied formulations, it can be pointed out that ∼24% of the of dietary supplements presented Tl concentrations at concentrations higher than 1 mg kg-1. The results permitted the assessment of the health risk related to thallium from contaminated samples, based on the calculation of the estimated daily intake (EDI) and the risk quotient (HQ). The highest daily intake of thallium was calculated as 82.0 µg day-1 in a protein-based supplement, which is equivalent to an EDI of 1.17 µg kg-1 day-1. This work highlights the need to develop regulations on the limits of toxic elements such as thallium in widely consumed dietary supplements, as well as an in-depth look at the adverse effects caused by this element in the human body.

Association of serum metal levels with type 2 diabetes: A prospective cohort and mediating effects of metabolites analysis in Chinese population.

Several studies have suggested an association between exposure to various metals and the onset of type 2 diabetes (T2D). However, the results vary across different studies. We aimed to investigate the associations between serum metal concentrations and the risk of developing T2D among 8734 participants using a prospective cohort study design. We utilized inductively coupled plasmamass spectrometry (ICP-MS) to assess the serum concentrations of 27 metals. Cox regression was applied to calculate the hazard ratios (HRs) for the associations between serum metal concentrations on the risk of developing T2D. Additionally, 196 incident T2D cases and 208 healthy control participants were randomly selected for serum metabolite measurement using an untargeted metabolomics approach to evaluate the mediating role of serum metabolite in the relationship between serum metal concentrations and the risk of developing T2D with a nested casecontrol study design. In the cohort study, after Bonferroni correction, the serum concentrations of zinc (Zn), mercury (Hg), and thallium (Tl) were positively associated with the risk of developing T2D, whereas the serum concentrations of manganese (Mn), molybdenum (Mo), barium (Ba), lutetium (Lu), and lead (Pb) were negatively associated with the risk of developing T2D. After adding these eight metals, the predictive ability increased significantly compared with that of the traditional clinical model (AUC: 0.791 vs. 0.772, P=8.85×10-5). In the nested casecontrol study, a machine learning analysis revealed that the serum concentrations of 14 out of 1579 detected metabolites were associated with the risk of developing T2D. According to generalized linear regression models, 7 of these metabolites were significantly associated with the serum concentrations of the identified metals. The mediation analysis showed that two metabolites (2-methyl-1,2-dihydrophthalazin-1-one and mestranol) mediated 46.81% and 58.70%, respectively, of the association between the serum Pb concentration and the risk of developing T2D. Our study suggested that serum Mn, Zn, Mo, Ba, Lu, Hg, Tl, and Pb were associated with T2D risk. Two metabolites mediated the associations between the serum Pb concentration and the risk of developing T2D.

Anthropogenic Forcing of the Baltic Sea Thallium Cycle.

Anthropogenic activities have fundamentally changed the chemistry of the Baltic Sea. According to results reported in this study, not even the thallium (Tl) isotope cycle is immune to these activities. In the anoxic and sulfidic ("euxinic") East Gotland Basin today, Tl and its two stable isotopes are cycled between waters and sediments as predicted based on studies of other redox-stratified basins (e.g., the Black Sea and Cariaco Trench). The Baltic seawater Tl isotope composition (ε205Tl) is, however, higher than predicted based on the results of conservative mixing calculations. Data from a short sediment core from East Gotland Basin demonstrates that this high seawater ε205Tl value originated sometime between about 1940 and 1947 CE, around the same time other prominent anthropogenic signatures begin to appear in the same core. This juxtaposition is unlikely to be coincidental and suggests that human activities in the surrounding area have altered the seawater Tl isotope mass-balance of the Baltic Sea.