Intracellular Fate of Sub-Toxic Concentration of Functionalized Selenium Nanoparticles in Aggressive Prostate Cancer Cells.

Selenium 0 (Se0) is a powerful anti-proliferative agent in cancer research. We investigated the impact of sub-toxic concentrations of Se0 functionalized nanoparticles (SeNPs) on prostate cancer PC-3 cells and determined their intracellular localization and fate. An in-depth characterization of functionalized selenium nanoparticles composition is proposed to certify that no chemical bias relative to synthesis issues might have impacted the study. Selenium is an extremely diluted element in the biological environment and therefore requires high-performance techniques with a very low detection limit and high spatial resolution for intracellular imaging. This was explored with state-of-the-art techniques, but also with cryopreparation to preserve the chemical and structural integrity of the cells for spatially resolved and speciation techniques. Monodisperse solutions of SeNPs capped with bovine serum albumin (BSA) were shown to slow down the migration capacity of aggressive prostate cancer cells compared to polydisperse solutions of SeNPs capped with chitosan. BSA coating could prevent interactions between the reactive surface of the nanoparticles and the plasma membrane, mitigating the generation of reactive oxygen species. The intracellular localization showed interaction with mitochondria and also a localization in the lysosome-related organelle. The SeNPs-BSA localization in mitochondria constitute a possible explanation for our result showing a very significant dampening of the PC-3 cell proliferation capabilities. The purpose of the use of sublethal compound concentrations was to limit adverse effects resulting from high cell death to best evaluate some cellular changes and the fate of these SeNPs on PC-3. Our findings provide new insight to further study the various mechanisms of cytotoxicity of SeNPs.

Immobilisation of contaminants by 'green'-synthesized magnetite as a remediation approach to the phosphogypsum waste leachates model solution.

Contaminant removal from (waste)waters by magnetite is a promising technology. In the present experimental study, a magnetite recycled from the steel industry waste (zero-valent iron powder) was used to investigate the sorption of As, Sb and U in phosphate-free and -rich suspensions, i.e. as a remediation for the acidic phosphogypsum leachates derived from the phosphate fertilizer industry. The results showed up to 98% U removal under controlled pH conditions, while phosphate did not hinder this immobilisation. In contrast, the results confirmed the limited uptake of As and Sb oxyanions by magnetite in presence of phosphate as the competing anion, displaying only 7-11% removal, compared to 83-87% in the phosphate-free sorption experiments. To limit this wastewater problem, raw ZVI anaerobic oxidation was examined as mechanism to increase the pH and as a source of Fe2+ in a first step, and in a second step to remove phosphate via vivianite precipitation, therefore prior to the reaction with magnetite. UV-Vis, XRD and SEM-EDS showed that vivianite precipitation is feasible at pH > 4.5, mainly depending on the phosphate concentration. The higher the [PO43-], the lower is the pH at which vivianite precipitates and the higher the % removal of phosphate from solution. It is anticipated that an optimum 3-steps design with separate reactors controlling the conditions of ZVI oxidation, followed by vivianite precipitation and finally, reaction with magnetite, can achieve high contaminant uptake in field applications.

Exploring carbonate rock wettability across scales: Role of (bio)minerals.

HYPOTHESIS: The wettability of carbonate rocks is expected to be affected by the organic components of biominerals which are complex, nanostructured organo-mineral assemblages. Elucidating the nanoscale mechanisms driving the wettability of solid surfaces will enable a better understanding of the role of biominerals in the wetting properties of carbonate rocks to control various geological, environmental and industrial processes. EXPERIMENTS: Using Atomic Force Microscopy and Spectroscopy (AFM/AFS) we probed the wettability properties of carbonate rocks with different amounts of organic material. The adhesion properties of two types of limestones were determined in liquid environments at different length scales (nm to mm) using functionalized tips with different chemical groups to determine the extent of surface hydrophobic and hydrophilic organo-mineral interactions. FINDINGS: We observed homogeneous hydrophobic areas at length scales below < 5 µm. The origin of this hydrophobicity is linked to the presence of organics, whose amount and spatial distribution depend on the rock composition. Specifically, our results reveal that the biogenic vs non-biogenic origin of the mineral grains is the main rock property controlling the wettability of the solid surface. Overall, our methodology offers a multi-scale approach to unravel the role that organic moieties and biominerals play in controlling the wettability of rock-water interfaces.

Selenium nanoparticles modulate histone methylation via lysine methyltransferase activity and S-adenosylhomocysteine depletion.

At physiological levels, the trace element selenium plays a key role in redox reactions through the incorporation of selenocysteine in antioxidant enzymes. Selenium has also been evaluated as a potential anti-cancer agent, where selenium nanoparticles have proven effective, and are well tolerated in vivo at doses that are toxic as soluble Se. The use of such nanoparticles, coated with either serum albumin or the naturally occurring alkaline polysaccharide chitosan, also serves to enhance biocompatibility and bioavailability. Here we demonstrate a novel role for selenium in regulating histone methylation in ovarian cancer cell models treated with inorganic selenium nanoparticles coated with serum albumin or chitosan. As well as inducing thioredoxin reductase expression, ROS activity and cancer cell cytotoxicity, coated nanoparticles caused significant increases in histone methylation. Specifically, selenium nanoparticles triggered an increase in the methylation of histone 3 at lysines K9 and K27, histone marks involved in both the activation and repression of gene expression, thus suggesting a fundamental role for selenium in these epigenetic processes. This direct function was confirmed using chemical inhibitors of the histone lysine methyltransferases EZH2 (H3K27) and G9a/EHMT2 (H3K9), both of which blocked the effect of selenium on histone methylation. This novel role for selenium supports a distinct function in histone methylation that occurs due to a decrease in S-adenosylhomocysteine, an endogenous inhibitor of lysine methyltransferases, the metabolic product of methyl-group transfer from S-adenosylmethionine in the one-carbon metabolism pathway. These observations provide important new insights into the action of selenium nanoparticles. It is now important to consider both the classic antioxidant and novel histone methylation effects of this key redox element in its development in cancer therapy and other applications.

Selenium Nanowire Formation by Reacting Selenate with Magnetite.

The mobility of 79Se, a fission product of 235U and long-lived radioisotope, is an important parameter in the safety assessment of radioactive nuclear waste disposal systems. Nonradioactive selenium is also an important contaminant of drainage waters from black shale mountains and coal mines. Highly mobile and soluble in its high oxidation states, selenate (Se(VI)O42-) and selenite (Se(IV)O32-) oxyanions can interact with magnetite, a mineral present in anoxic natural environments and in steel corrosion products, thereby being reduced and consequently immobilized by forming low-solubility solids. Here, we investigated the sorption and reduction capacity of synthetic nanomagnetite toward Se(VI) at neutral and acidic pH, under reducing, oxygen-free conditions. The additional presence of Fe(II)aq, released during magnetite dissolution at pH 5, has an effect on the reduction kinetics. X-ray absorption spectroscopy analyses revealed that, at pH 5, trigonal gray Se(0) formed and that sorbed Se(IV) complexes remained on the nanoparticle surface during longer reaction times. The Se(0) nanowires grew during the reaction, which points to a complex transport mechanism of reduced species or to active reduction sites at the tip of the Se(0) nanowires. The concomitant uptake of aqueous Fe(II) and Se(VI) ions is interpreted as a consequence of small pH oscillations that result from the Se(VI) reduction, leading to a re-adsorption of aqueous Fe(II) onto the magnetite, renewing its reducing capacity. This effect is not observed at pH 7, where we observed only the formation of Se(0) with slow kinetics due to the formation of an oxidized maghemite layer. This indicates that the presence of aqueous Fe(II) may be an important factor to be considered when examining the environmental reactivity of magnetite.

Ab initio modeling of H2S dissociative chemisorption on Ag(100).

Natural sulfidation of silver nanomaterials can passivate the surface, while preserving desirable optical and electrical properties, which is beneficial for limiting Ag+ release and cytotoxicity. But little is known at the atomic scale about silver sulfidation mechanisms, particularly on different crystallographic terminations. Using density functional theory (DFT) calculations, we examined the process of H2S sorption and reaction on Ag(100) surfaces relevant to Ag nanowires (AgNWs). DFT energy minimizations predict a strong dissociative chemisorption of H2S on the surface yielding co-adsorbed sulfide and hydrogen atoms in specific surface sites. However, nudged elastic band (NEB) calculations suggest relatively large activation energies for both the first and second dissociation steps, due in part to overcoming the energy to cleave the S-H bond and attendant site migration from an on-top Ag site position to a hollow site position of the bound S atom. The large barriers associated with the dissociative chemisorption reaction for gas-phase H2S points to the importance of including thermochemical contributions and the influence of other components in more complex environmental media such as air or water to help complete the mechanistic picture of silver sulfidation and passivation for realistic systems.

Redox Interaction between Selenite and Mackinawite in Cement Pore Water.

In cement-rich radioactive waste repositories, mackinawite (FeS) forms at the steel corrosion interface within reinforced concrete and potentially retards the transport of redox-sensitive radionuclides (e.g., 79Se) in porous cement media. Redox interactions between selenite and mackinawite under hyperalkaline conditions remain unclear and require further investigations. Here, using comprehensive characterization on both aqueous and solid speciation, we successfully monitored the whole interaction process between selenite and mackinawite under hyperalkaline conditions. The results show similar chemical environments for SeO32- and S2-/Sn2- at the mackinawite-water interface, verifying an immediate reduction. After 192 h of reaction, SeO32- was reduced to solid Se0 and SeS2 species, accompanied by the oxidation of S2-/Sn2- to S2O32- and Fe(II) to Fe(III) in mackinawite. Aqueous speciation results showed that ∼99% of aqueous selenium was present as Se4S nanoparticles due to the dissolution of Se from the solid. In parallel, ∼62% of S2-/Sn2- was released into the solution, with mackinawite transforming into magnetite, Fe(OH)3 and FeS2O3+ complexed to Cl- or OH- species, and magnetite subsequently dispersed in the solution. This study provides valuable data about the retardation mechanisms of redox-sensitive radionuclides by soluble iron sulfides, which is critical to advance our understanding of reactive concrete barriers used in nuclear waste disposal systems.

In Vitro Preparation of Actively Maturing Bovine Articular Cartilage Explants for X-Ray Phase Contrast Imaging.

Understanding the mechanisms that underpin post-natal maturation of articular cartilage is of crucial importance for designing the next generation of tissue engineering strategies and potentially repairing diseased or damaged cartilage. In general, postnatal maturation of the articular cartilage, which is a wholesale change in collagen structure and function of the tissue to accommodate growth of the organism, occurs over a timescale ranging from months to years. Conversely dissolution of the structural organization of the cartilage that also occurs over long timescales is the hallmark of tissue degeneration. Our ability to study these biological processes in detail have been enhanced by the findings that growth factors can induce precocious in vitro maturation of immature articular cartilage. The developmental and disease related changes that occur in the joint involve bone and cartilage and an ability to co-image these tissues would significantly increase our understanding of their intertwined roles. The simultaneous visualization of soft tissue, cartilage and bone changes is nowadays a challenge to overcome for conventional preclinical imaging modalities used for the joint disease follow-up. Three-dimensional X-ray Phase-Contrast Imaging methods (PCI) have been under perpetual developments for 20 years due to high performance for imaging low density objects and their ability to provide additional information compared to conventional X-ray imaging. In this protocol we detail the procedure used in our experiments from biopsy of the cartilage, generation of in vitro matured cartilage to data analysis of image collected using X-ray phase contrast imaging.

DNA Double-Strand Breaks Induced in Human Cells by 6 Current Pesticides: Intercomparisons and Influence of the ATM Protein.

A mechanistic model from radiobiology has emerged by pointing out that the radiation-induced nucleo-shuttling of the ATM protein (RIANS) initiates the recognition, the repair of DNA double-strand breaks (DSB), and the final response to genotoxic stress. More recently, we provided evidence in this journal that the RIANS model is also relevant for exposure to metal ions. To document the role of the ATM-dependent DSB repair and signaling after pesticide exposure, we applied six current pesticides of domestic and environmental interest (lindane, atrazine, glyphosate, permethrin, pentachlorophenol and thiabendazole) to human skin fibroblast and brain cells. Our findings suggest that each pesticide tested may induce DSB at a rate that depends on the pesticide concentration and the RIANS status of cells. At specific concentration ranges, the nucleo-shuttling of ATM can be delayed, which impairs DSB recognition and repair, and contributes to toxicity. Interestingly, the combination of copper sulfate and thiabendazole or glyphosate was found to have additive or supra-additive effects on DSB recognition and/or repair. A general mechanistic model of the biological response to metal and/or pesticide is proposed to define quantitative endpoints for toxicity.

DNA Double-Strand Breaks Induced in Human Cells by Twelve Metallic Species: Quantitative Inter-Comparisons and Influence of the ATM Protein.

Despite a considerable amount of data, the molecular and cellular bases of the toxicity due to metal exposure remain unknown. Recent mechanistic models from radiobiology have emerged, pointing out that the radiation-induced nucleo-shuttling of the ATM protein (RIANS) initiates the recognition and the repair of DNA double-strand breaks (DSB) and the final response to genotoxic stress. In order to document the role of ATM-dependent DSB repair and signalling after metal exposure, we applied twelve different metal species representing nine elements (Al, Cu, Zn Ni, Pd, Cd, Pb, Cr, and Fe) to human skin, mammary, and brain cells. Our findings suggest that metals may directly or indirectly induce DSB at a rate that depends on the metal properties and concentration, and tissue type. At specific metal concentration ranges, the nucleo-shuttling of ATM can be delayed which impairs DSB recognition and repair and contributes to toxicity and carcinogenicity. Interestingly, as observed after low doses of ionizing radiation, some phenomena equivalent to the biological response observed at high metal concentrations may occur at lower concentrations. A general mechanistic model of the biological response to metal exposure based on the nucleo-shuttling of ATM is proposed to describe the metal-induced stress response and to define quantitative endpoints for toxicity and carcinogenicity.

Copper Isotopes and Copper to Zinc Ratio as Possible Biomarkers for Thyroid Cancer.

Thyroid cancer is the most common endocrine cancer. There is no systematic screening for such cancer, and the current challenge is to find potential biomarkers to facilitate an early diagnosis. Copper (Cu) and zinc (Zn) are essential micronutrients involved in the proper functioning of the thyroid gland, and changes in their concentrations have been observed in the development of cancer. Previous studies have highlighted the potential 65Cu/63Cu ratio (δ65Cu) to be a cancer biomarker. This study tests its sensitivity on plasma samples (n = 46) of Algerian patients with papillary thyroid carcinoma and a set of corresponding biopsies (n = 11). The δ65Cu ratio in blood and tumor samples was determined using multi collector inductively coupled plasma-mass spectrometry (MC-ICP-MS), and their corresponding Cu and Zn plasma total concentrations using total reflection X-ray fluorescence (TXRF). Plasma concentrations of Cu were significantly higher (1346.1 ± 328.3 vs. 1060.5 ± 216.1 µg/L, p < 0.0001), and Zn significantly lower (942.1 ± 205.2 vs. 1027.9 ± 151.4 µg/L, p < 0.05) in thyroid cancer patients as compared to healthy controls (n = 50). Accordingly, the Cu/Zn ratio was significantly different between patients and controls (1.5 ± 0.4 vs. 1.0 ± 0.3, p < 0.0001). Furthermore, the δ65Cu plasma levels of patients were significantly lower than healthy controls (p < 0.0001), whereas thyroid tumor tissues presented high δ65Cu values. These results support the hypothesis that Cu isotopes and plasma trace elements may serve as suitable biomarkers of thyroid cancer diagnosis.

Acid volatile sulfides and simultaneously extracted metals: A new miniaturized 'purge and trap' system for laboratory and field measurements.

In natural environments, Acid Volatile Sulfides (AVS) contained in anoxic waters or sediments, are composed of dissolved sulfides and neo-formed sulfides colloids or particles. Under acidic addition, AVS emit hydrogen sulfide gas and release the so-called simultaneously extracted metals (SEM). The measurement of AVS coupled with that of the SEM enables to evaluate the metal trapping capacity of sulfides in the environment. Because AVS are extremely reactive to oxidation, the most accurate methodology to quantify AVS and SEM requires to be able to process the samples extraction on-site, directly after sampling and avoiding oxygen exposure. However, most of available systems are based on glassware 'purge and trap' techniques developed for the laboratory and are not often adapted to field studies. In these systems, AVS extraction time can range from 30 min to 3 h with relative standard deviation from 7 to 44%. In this study, we developed a new 'purge and trap' system designed for both laboratory use and field AVS/SEM extractions. The system is optimized with a shortened extraction time, miniaturized, unbreakable, easy and reproducible to develop parallel extraction benches. Analytical yields, precision and stability have been improved, allowing to reduce the extraction time to 1 h with an absolute quantification limit of 0.12 µmol S(-II) with a relative standard deviation between 7 and 11% and under a complete extraction efficiency.

Influence of Silica Coatings on Magnetite-Catalyzed Selenium Reduction.

The reactivity of iron(II/III) oxide surfaces may be influenced by their interaction with silica, which is ubiquitous in aquatic systems. Understanding the structure-reactivity relationships of Si-coated mineral surfaces is necessary to describe the complex surface behavior of nanoscale iron oxides. Here, we use Si-adsorption isotherms and Fourier transform infrared spectroscopy to analyze the sorption and polymerization of silica on slightly oxidized magnetite nanoparticles (15% maghemite and 85% magnetite, i.e., ∼2 maghemite surface layers), showing that Si adsorption follows a Langmuir isotherm up to 2 mM dissolved Si, where surface polymerization occurs. Furthermore, the effects of silica surface coatings on the redox-catalytic ability of magnetite are analyzed using selenium as a molecular probe. The results show that for partially oxidized nanoparticles and even under different Si surface coverages, electron transfer is still occurring. The results indicate anion exchange between silicate and the sorbed SeIV and SeVI. X-ray absorption near-edge structure analyses of the reacted Se indicate the formation of a mixed selenite/Se0 surface phase. We conclude that neither partial oxidation nor silica surface coatings block the sorption and redox-catalytic properties of magnetite nanoparticles, a result with important implications to assess the reactivity of mixed-valence phases in environmental settings.

Se Status Prediction by Food Intake as Compared to Circulating Biomarkers in a West Algerian Population.

Algeria is the largest country in Africa, located close to the Mediterranean coastal area, where nutrients consumption varies widely. Local data on selenium composition of foods are not available. We postulated a close correlation between selenium status predictions from food consumption analysis with a quantitative analysis of circulating biomarkers of selenium status. Population characteristics were recorded from 158 participants and dietary selenium intake was calculated by 24-h recall. The average total plasma selenium was 92.4 ± 18.5 µg/L and the mean of selenium intake was 62.7 µg/day. The selenoprotein P concentration was 5.5 ± 2.0 mg/L and glutathione peroxidase 3 activity was 247.3 ± 41.5 U/L. A direct comparison of the dietary-derived selenium status to the circulating selenium biomarkers showed no significant interrelation. Based on absolute intakes of meat, potato and eggs, a model was deduced that outperforms the intake composition-based prediction from all food components significantly (DeLong's test, p = 0.029), yielding an area under the curve of 82%. Selenium status prediction from food intake remains a challenge. Imprecision of survey method or information on nutrient composition makes extrapolating selenium intake from food data providing incorrect insights into the nutritional status of a given population, and laboratory analyses are needed for reliable information.

Selenium nanoparticles trigger alterations in ovarian cancer cell biomechanics.

High dose selenium acts as a cytotoxic agent, with potential applications in cancer treatment. However, clinical trials have failed to show any chemotherapeutic value of selenium at safe and tolerated doses (<90 µg/day). To enable the successful exploitation of selenium for cancer treatment, we evaluated inorganic selenium nanoparticles (SeNP), and found them effective in inhibiting ovarian cancer cell growth. In both SKOV-3 and OVCAR-3 ovarian cancer cell types SeNP treatment resulted in significant cytotoxicity. The two cell types displayed contrasting nanomechanical responses to SeNPs, with decreased surface roughness and membrane stiffness, characteristics of OVCAR-3 cell death. In SKOV-3, cell membrane surface roughness and stiffness increased, both properties associated with decreased metastatic potential. The beneficial effects of SeNPs on ovarian cancer cell death appear cell type dependent, and due to their low in vivo toxicity offer an exciting opportunity for future cancer treatment.

Influence of Surface Compositions on the Reactivity of Pyrite toward Aqueous U(VI).

Pyrite plays a significant role in governing the mobility of toxic uranium in an anaerobic environment via an oxidation-reduction process occurring at the mineral-water interface, but the factors influencing the reaction kinetics remain poorly understood. In this study, natural pyrites with different impurities (Pb, As, and Si) and different surface pretreatments were used to react with aqueous U(VI) from pH ∼3.0 to ∼9.5. Both aqueous and solid results indicated that freshly crushed pyrites, which do have more surface Fe2+/Fe3+ and S2- sites that were generated from breakage of Fe(S)-S bonds during ball milling, exhibited a much stronger reactivity than those treated with acid washing. Besides, U(VI) reduction which involves the possible intermediate U(V) and the formation of hyperstoichiometric UO2+x(s) was found to preferentially occur at Pb- and As-rich spots on the pyrite surface, suggesting that the incorporated impurities could act as reactive sites because of the generation of lattice defects and galena- and arsenopyrite-like local configurations. These reactive surface sites can be removed by acid washing, leaving a pyrite surface nearly inert toward aqueous U(VI). Thus, reactivity of pyrite toward U(VI) is largely governed by its surface compositions, which provides an insight into the chemical behavior of both pyrite and uranium in various environments.

Selenite Sorption on Hydrated CEM-V/A Cement in the Presence of Steel Corrosion Products: Redox vs Nonredox Sorption.

Reinforced cementitious structures in nuclear waste repositories will act as barriers that limit the mobility of radionuclides (RNs) in case of eventual leakage. CEM-V/A cement, a ternary blended cement with blast furnace slag (BFS) and fly ash (FA), could be qualified and used in nuclear waste disposal. Chemical interactions between the cement and RNs are critical but not completely understood. Here, we combined wet chemistry methods, synchrotron-based X-ray techniques, and thermodynamic modeling to explore redox interactions and nonredox sorption processes in simulated steel-reinforced CEM-V/A hydration systems using selenite as a molecular probe. Among all of the steel corrosion products analyzed, only the addition of Fe0 can obviously enhance the reducing ability of cement toward selenite. In comparison, steel corrosion products showed stronger reducing power in the absence of cement hydrates. Selenium K-edge X-ray absorption spectroscopy (XAS) revealed that selenite immobilization mechanisms included nonredox inner-/outer-sphere complexations and reductive precipitations of FeSe and/or Se(0). Importantly, the hydrated pristine cement showed a good reducing ability, driven by ferrous phases and (bi)sulfides (as shown by sulfur K-edge XAS) originated from BFS and FA. The overall redox potential imposed by hydrated CEM-V/A was determined, hinting to a redox shift in underground cementitious structures.

Effects of redox oscillations on the phosphogypsum waste in an estuarine salt-marsh system.

Salt marshes are natural deposits of heavy metals in estuarine systems, where sulphide precipitation associated with redox changes often results in a natural attenuation of contamination. In the present study, we focus on the effects of variable redox conditions imposed to a highly-polluted phosphogypsum stack that is directly piled over the salt marsh soil in the Tinto River estuary (Huelva, Spain). The behaviour of contaminants is evaluated in the phosphogypsum waste and in the marsh basement, separately, in controlled, experimentally-induced oscillating redox conditions. The results revealed that Fe, and to a lesser extent S, control most precipitation/dissolution processes. Ferric iron precipitates in the form of phosphates and oxyhydroxides, while metal sulphide precipitation is insignificant and appears to be prevented by the abundant formation of Fe phosphates. An antagonistic evolution with changing redox conditions was observed for the remaining contaminants such as Zn, As, Cd and U, which remained mobile in solution during most of experimental run. Therefore, these findings revealed that high concentrations of phosphates inhibit the typical processes of immobilisation of pollutants in salt-marshes which highlights the elevated contaminant potential of phosphogypsum wastes on coastal environments.

Crumpling of silver nanowires by endolysosomes strongly reduces toxicity.

Fibrous particles interact with cells and organisms in complex ways that can lead to cellular dysfunction, cell death, inflammation, and disease. The development of conductive transparent networks (CTNs) composed of metallic silver nanowires (AgNWs) for flexible touchscreen displays raises new possibilities for the intimate contact between novel fibers and human skin. Here, we report that a material property, nanowire-bending stiffness that is a function of diameter, controls the cytotoxicity of AgNWs to nonimmune cells from humans, mice, and fish without deterioration of critical CTN performance parameters: electrical conductivity and optical transparency. Both 30- and 90-nm-diameter AgNWs are readily internalized by cells, but thinner NWs are mechanically crumpled by the forces imposed during or after endocytosis, while thicker nanowires puncture the enclosing membrane and release silver ions and lysosomal contents to the cytoplasm, thereby initiating oxidative stress. This finding extends the fiber pathology paradigm and will enable the manufacture of safer products incorporating AgNWs.

Plate tectonics influence on geogenic arsenic cycling: From primary sources to global groundwater enrichment.

More than 100 million people around the world are endangered by geogenic arsenic (As) in groundwater, residing in sedimentary aquifers. However, not all sedimentary aquifers are groundwater As enriched, and the ultimate source of As in enriched aquifer sediments is yet-unknown, globally. A reconnaissance of the major aquifers suggests that major As enriched aquifers are predictably systematic on a global scale, existing in sedimentary foreland basins in the vicinity of modern or ancient orogenic systems. In conformity with the Principle of Uniformitarianism, we demonstrate that the groundwater As comes from magmatic arcs (primary source) in present (e.g. Andes) or ancient (e.g. Himalaya) continental convergent margins of some of the most prominent orogenic systems across the globe, and ends up in sediments (secondary source) in adjoining foreland or related basins that eventually act as aquifers. These arc magmas scavenge As while rising through the deep continental crust. Erosion of such orogens ultimately increases the bulk As content in sediments of adjoining basins, leading to groundwater As enrichment in downstream aquifers. Such As-polluted aquifers are eventually extensively used for groundwater exploitation, for drinking and other human purposes. Surface geological and biogeochemical processes, like redox reactions, are conducive to such groundwater As enrichment. We suggest this model by integrating our study of long-time observations in Himalayan and Andean basin aquifers, and generalizing 63 major aquifers across the globe, to demonstrate the source-to-sink transport of As, thereby delineating it's geogenic cycling in the subsurface. This work outlines the specifics of the mechanisms that would drive the processes of groundwater As enrichment across spatio-temporal scales, i.e. tectonic-scale taking place over millions of years on continental-scale and groundwater pollution taking place at human time-scales on village to household scale. Thus, in this work, we demonstrate a direct evidence of connectivity between global geological processes and individual human health.