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Articles published on Metal Depletion

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  • Research Article
  • 10.47772/ijriss.2025.91100388
Cradle-To-Gate Environmental Impact Assessment of EDM Wire-Cut and Laser Cutting Processes
  • Dec 11, 2025
  • International Journal of Research and Innovation in Social Science
  • Umi Hayati Ahmad + 3 more

Non-traditional machining (NTM) processes, such as EDM wire-cut and laser cutting, are widely used in manufacturing for their ability to machine complex geometries and hard-to-cut materials. Despite their operational advantages, the environmental implications of these processes remain insufficiently understood. This study develops a structured cradle-to-gate environmental assessment framework to enable a systematic and reproducible comparison between EDM wire-cut and laser cutting for the production of an identical wrench component from mild steel. The framework is organised into sequential stages, including process selection, functional unit and system boundary definition, inventory data collection, and impact modelling using GaBi software. Key impact categories considered include Climate Change, Metal Depletion, Human Toxicity (Cancer), Ionising Radiation, and Freshwater Eutrophication. Results indicate that EDM wire-cut environmental impacts are primarily driven by electricity consumption and wire usage, whereas laser cutting impacts are dominated by high power demand and assist-gas consumption. The study highlights critical process parameters affecting environmental performance and identifies opportunities for impact reduction through optimized machine settings and resource usage. The novelty of this work lies in the introduction of a structured LCA framework tailored specifically for non-traditional machining, providing clear comparative evidence to support more informed and sustainable process selection. These findings offer practical guidance for manufacturers aiming to reduce environmental footprints while maintaining production efficiency.

  • Research Article
  • 10.1093/inteam/vjaf161
Environmental assessment of municipal solid waste composting: Comparing landfilling and incineration scenarios towards a sustainable approach.
  • Dec 8, 2025
  • Integrated environmental assessment and management
  • Hajar Abyar + 4 more

Driven by the high contents of organic materials in municipal solid waste (MSW) by 70% in Iran and the growing demand for mineral fertilizer, refinement of the composting technology is imperative. In the pursuit of environmental sustainability, further investigation into the life cycle assessment of the composting process and end-of-life waste management must be conducted. Hence, this study scrutinized the environmental burdens of the composting plant operation from cradle to gate. Since 50% of the raw MSW was not converted to compost, its final disposal was evaluated based on incineration, landfill, and integrated approaches. The results indicated marine and freshwater ecotoxicity of the composting process (> 50.4 kg 1,4-DB eq). Heavy metal and gas emissions during the MSW decomposition were the pivotal parameters for most impact categories. CO2 emission intensified climate change by 3523 kg CO2 eq; however, waste incineration led to emission savings of 98.75%. The environmental benefits of incineration were observed in 13 impact categories alongside a net-negative value for natural land transformation. Landfilling also induced savings in freshwater eutrophication and metal depletion by 98.67% and 99.08%, respectively. Unlike previous studies relying on generalized data, this study uses detailed, plant-level operational data and scenario-based modeling from Sistan and Baluchestan province. This approach provides realistic impact estimates and decision-relevant insights.

  • Research Article
  • 10.3847/1538-4357/ae10a6
Ionization Sources of the Local Interstellar Clouds: Two B Stars, Three White Dwarfs, and the Local Hot Bubble
  • Nov 24, 2025
  • The Astrophysical Journal
  • J Michael Shull + 3 more

Abstract The dominant sources of photoionizing radiation in the extreme-ultraviolet (EUV) incident on the exterior of the local interstellar clouds include two nearby early B-type stars, ϵ CMa (124 ± 2 pc) and β CMa (151 ± 5 pc), three hot dwarfs, and the Local Hot Bubble (LHB). Line emission (170–912 Å) from highly ionized metals (Fe, Ne, Mg) in million-degree LHB plasma may be responsible for the elevated ionization fractions of helium ( n He II / n He ≈ 0.4) compared to hydrogen ( n H II / n H ≈ 0.2) in the local clouds. We update the stellar parameters and ionizing flux for β CMa, after correcting the EUV spectra for intervening H i column density, N H I = (1.9 ± 0.1) × 10 18 cm −2 , and its hotter effective temperature, T eff ≈ 25,000 K versus 21,000 K for ϵ CMa. These two stars produce a combined H-ionizing photon flux Φ H ≈ 6800 ± 1400 cm −2 s −1 at the external surface of the local clouds. The hot bubble could produce comparable fluxes, Φ H = 2000–9000 cm −2 s −1 , depending on the amount of metal depletion into dust grains that survive sputtering. The radial velocities and proper motions of β CMa and ϵ CMa indicate that both stars passed within 10 ± 1 pc of the Sun 4.4 ± 0.1 Myr ago, with 100–200 times higher local ionizing fluxes. At that time, the local clouds were likely farther from the Sun, owing to their transverse motion. Over the past few Myr, EUV radiation from these two stars left a wake of highly ionized gas in a hot, low-density cavity produced by past supernova explosions in the Sco-Cen OB association and connected with the LHB.

  • Research Article
  • 10.1038/s41598-025-25013-4
Uncovering the molecular details of the 14-3-3 recruitment by mutant Sod1 species
  • Nov 20, 2025
  • Scientific Reports
  • Lorenzo Di Rienzo + 4 more

Mutations in superoxide dismutase 1 (SOD1) are a major cause of familial Amyotrophic Lateral Sclerosis (ALS), promoting disease progression through metal depletion, aggregation, and abnormal protein interactions. Among proteins interacting with pathological SOD1 aggregates, 14-3-3 proteins are involved in key cellular pathways often disrupted in ALS, such as cell survival, axonal growth, and DNA repair. Their sequestration by mutant SOD1 may impair their neuroprotective functions, exacerbating disease pathology. Despite this, 14-3-3 proteins remain understudied in ALS research, presenting an opportunity for novel insights. This study employs molecular dynamics simulations to investigate structural changes in two ALS-linked SOD1 mutations, A4V and L144F, compared to wild-type SOD1. A4V is associated with a severe disease form, while L144F leads to a slower progression, allowing an analysis of different ALS severities. Using Zernike polynomials and hydropathy assessments, we identified key structural alterations that promote aggregation and aberrant interactions. Large-scale docking simulations further suggest a stable complex between mutant SOD1 and 14-3-3 proteins, confirmed through molecular dynamics analyses. By elucidating structural features driving SOD1 aggregation and pathological interactions, our findings support targeting protein-protein interactions as a potential therapeutic strategy in ALS, offering an alternative to direct aggregate inhibition.

  • Research Article
  • 10.1016/j.scitotenv.2025.180690
Environmental and economic assessment of the implementation of an automated nuclear interim waste store using novel monitoring platforms.
  • Nov 15, 2025
  • The Science of the total environment
  • Rachael Clayton + 5 more

Environmental and economic assessment of the implementation of an automated nuclear interim waste store using novel monitoring platforms.

  • Research Article
  • 10.1088/1742-6596/3140/13/132002
Comparative environmental assessment of heat pumps and gas boilers under evolving electricity mixes and climate change: A Case Study of a Residential Building in London
  • Nov 1, 2025
  • Journal of Physics: Conference Series
  • Kordilas Marios + 4 more

Abstract This study compares the environmental performance of 18 impacts of a timber structured residential building in London, when heating and DHW are either provided by a heat pump or a condensing gas boiler by considering the dynamic effects of climate change and electricity mix evolution. A Life Cycle Assessment (LCA) approach was followed. To accurately describe future electricity mixes relevant for embodied and operational modules, the Life Cycle Inventory (LCI) was modified reflecting future projections for the UK, EU and China. The influence of climate change was considered through dynamic thermal simulations using London’s future climatic projections. Results show a general reducing trend in the building’s heating demand driving the overall energy needs of module B6 of EN15978 down. Switching to a heat pump makes the building perform significantly better in terms of lifecycle carbon, land transformation and fossil depletion benefiting from grid decarbonisation. However, the pressure on several beyond carbon impacts such as ozone depletion, ecotoxicity, eutrophication and metal depletion intensifies. This highlights the need for a holistic approach when switching technologies towards Net Zero to avoid trade-offs. As most beyond carbon impacts that expect intensified pressure are geographically specific, future research is needed to examine whether more granular data will corroborate this study’s trends. This is to help assess whether the pressure on beyond carbon impacts is of concerning magnitude. Finally, although the installation of active cooling devices was not considered for comparability consistency, results show cooling demand might become important in future.

  • Research Article
  • 10.1093/jambio/lxaf258
Antibacterial chelating agents with applications in industry and medicine: cellular metal restriction, membrane disruption, and synergism with antibiotics in Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens, Bacillus subtilis, and Staphylococcus aureus.
  • Oct 16, 2025
  • Journal of applied microbiology
  • Joy R Paterson + 11 more

Chelating agents are metal-sequestering compounds with antibacterial properties suitable for commercial and therapeutic applications. This study investigated the involvement of metal restriction and membrane disruption in the antibacterial mode of action of three chelators. The antibacterial, metal sequestration, and membrane disruptive effects of ethylenediaminetetraacetic acid, diethylenetriamine pentamethylene phosphonic acid, and fusaric acid were examined across five bacterial species. ICP-MS was used to determine the impact on bacterial metal composition, while RT-qPCR of selected genes allowed evaluation of changes in cellular responses to intracellular metal depletion. Mutants defective in metal import and export machinery were also examined to validate processes critical for resistance. Chelator-mediated disruption of membranes was investigated using 1-N-phenylnapthylamine and propidium iodide. Finally, the capacity of two of the chelators to potentiate the activity of ampicillin, chloramphenicol, tetracycline, and three aminoglycosides was assessed in chequerboards. The results show that these chelators restrict access to iron, zinc, manganese, and calcium to varying degrees in these bacterial species, reflecting important differences in envelope architectures and metal handling capabilities. This study shows that all three chelators behave differently in restricting metal access and possess antibacterial properties that often act synergistically in combination, notably with other antimicrobials.

  • Research Article
  • 10.1053/j.ajkd.2025.08.010
Environmental Impacts of Kidney Replacement Therapies: A Comparative Lifecycle Assessment.
  • Oct 1, 2025
  • American journal of kidney diseases : the official journal of the National Kidney Foundation
  • Saba Saleem + 6 more

Environmental Impacts of Kidney Replacement Therapies: A Comparative Lifecycle Assessment.

  • Research Article
  • 10.1088/1742-6596/3131/1/012043
A prospective life cycle assessment of drivetrain technologies in offshore wind
  • Oct 1, 2025
  • Journal of Physics: Conference Series
  • Vinit V Dighe + 4 more

Abstract This study employs a prospective life cycle assessment (pLCA) to evaluate the environmental impacts of two drivetrain configurations, direct drive (DD) and medium-speed (MS), at the wind farm level across the entire life cycle. The assessment considers how environmental impacts evolve in the future, reflecting projected changes in macroeconomic indicators and climate targets. The DD configuration shows higher impacts in the material extraction and production phase due to its reliance on critical metals and rare earth elements, which is also offset in the long term through recycling benefits at the end-of-life (EOL) stage. In contrast, the MS configuration has greater emissions during operations, requiring more drivetrain-related maintenance and component replacements, while the DD configuration benefits from lower maintenance demands. The total climate change impact for DD is 6.8 g CO 2 -eq/kWh, while for MS, it is slightly higher at 7.1 g CO 2 -eq/kWh. A comparison of static LCA and pLCA highlights key differences, particularly in the operational phase, where pLCA indicates lower emissions due to anticipated improvements in supply chains, such as greater use of renewable-powered refineries for vessel fuel. However, pLCA accounts for recycling benefits over time rather than immediately, leading to lower avoided burdens at EOL compared to static LCA. Beyond climate change, metal depletion is a key impact category, with DD showing a 12% higher impact due to its reliance on copper and rare earth elements, while MS exhibits higher emissions from fuel-intensive operations. This study demonstrates the prospective approach for conducting LCA, emphasizing the importance of integrating future technologies and processes in environmental impact assessments for offshore wind.

  • Research Article
  • 10.1016/j.scitotenv.2025.180393
Life cycle assessment of large-scale integrated organic crop-egg production in Brazil.
  • Oct 1, 2025
  • The Science of the total environment
  • Michelle Savian + 1 more

Life cycle assessment of large-scale integrated organic crop-egg production in Brazil.

  • Research Article
  • Cite Count Icon 1
  • 10.1038/s41598-025-16300-1
Life cycle assessment of high value activated carbon production based on mass and functional performance metrics
  • Sep 25, 2025
  • Scientific Reports
  • Junaid Saleem + 5 more

The production of activated carbon (AC) from biomass holds substantial environmental potential, but its impact varies widely depending on the synthesis methods employed. However, unreliable experimental data results in inconsistent life cycle assessments (LCA), often dependent on generic or highly localized information. Most available data focuses solely on production metrics, neglecting crucial performance-based indicators. This study conducts LCA for a conceptual AC production facility designed to produce 1 kg of AC per batch of coconut shell (CS), particularly examining potassium hydroxide (KOH) and sodium hydroxide (NaOH) activation routes. Environmental impacts (EIs) are evaluated using two functional units—mass-based and adsorption-based—and span eighteen metrics, including six key ones: net energy, climate change (CC), ozone depletion, fine particulate matter formation, marine eutrophication, and metal depletion. CC (kg CO₂ eq.) for 1 kg of AC production is 1.255 for KOH and 1.209 for NaOH, while energy requirements (in MJ) are 28.314 for KOH and 27.063 for NaOH. Notably, the pyrolysis step emerges as the most energy-intensive and significant contributor to carbon emissions. Per the adsorption-based unit, the KOH-led pathway shows a higher adsorption capacity of 729 g/kg versus 662 g/kg for NaOH, requiring less AC per kg of dye adsorbed. Consequently, the KOH pathway achieves 5% greater energy efficiency and 6% lower carbon emissions than the NaOH pathway. Synthesized ACs outperform commercial AC in all metrics, especially in energy use and carbon emissions. The study proposes improvements, such as alternative drying methods, to mitigate EIs and emphasizes the need to consider both production efficiency and functional performance to guide sustainable AC production and application.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-16300-1.

  • Research Article
  • 10.33927/hjic-2025-13
Life Cycle Assessment of Technological Shifts in Municipal Wastewater Treatment Plants
  • Sep 10, 2025
  • Hungarian Journal of Industry and Chemistry
  • Réka Harasztiné Hargitai + 3 more

The challenges faced by municipal wastewater treatment plants (WWTPs) to improve effluent quality while reducing environmental impacts are increasing. This study employs a Life Cycle Assessment to evaluate the development of effluent water quality and overall environmental impacts through seven years of technological advancements at a WWTP using real world data. Scenarios include biogas optimization, transitioning to biological phosphorus removal, solar energy integration, optimized effluent control and hypothetical quaternary wastewater treatments (ozonation and sequential H2O2 treatment). Transitioning to biological phosphorus removal reduced chemical use by 26.2% and achieved the highest nutrient removal efficiency but increased energy consumption, slightly raising fossil depletion (FD). Solar energy reduced FD by 18.4% and contributed 7.75% of energy needs, albeit with seasonal limitations. Optimized effluent control achieved the highest level of nutrient removal, improving freshwater eutrophication by 41.4% but increased sludge production by 10.4%, leading to a 23.9% rise in metal depletion. Ozonation significantly increased environmental burdens, while sequential H2O2 treatment had less of an impact, offering future potential for wastewater reuse. The findings underscore the importance of balancing energy, chemical use and effluent quality with biogas optimization playing a key role in reducing flaring. This study highlights the trade-offs inherent in WWTP upgrades and provides actionable insights into optimizing environmental performance.

  • Research Article
  • 10.1128/msystems.00576-25
Calprotectin protects Staphylococcus aureus in coculture with Pseudomonas aeruginosa by attenuating quorum sensing and decreasing the production of pseudomonal antimicrobials
  • Sep 4, 2025
  • mSystems
  • Wei H Lee + 2 more

Pseudomonas aeruginosa and Staphylococcus aureus cause debilitating polymicrobial infections in diverse patient populations. Studies of these bacterial pathogens in coculture have shown that environmental variables, including Fe availability and the host-defense protein calprotectin (CP), impact coculture dynamics. To decipher how CP modulates interactions between P. aeruginosa and S. aureus, we employed dual-species RNA-seq to examine the transcriptional responses of both pathogens in coculture to CP treatment and metal depletion. Analysis of these responses revealed that, for both P. aeruginosa and S. aureus, CP treatment not only induced gene expression changes consistent with single- and multi-metal starvation responses but also induced gene expression changes that were not observed under metal limitation. For P. aeruginosa, CP treatment induced gene expression changes pointing to a shift in chorismate flux away from alkylquinolone and phenazine biosynthesis and toward folate biosynthesis. These observations were consistent with decreased production of alkylquinolones by P. aeruginosa, including the potent anti-staphylococcal alkylquinolone N-oxides. CP treatment altered the levels of two quorum-sensing molecules, 3-oxo-C12-homoserine lactone and C4-homoserine lactone, produced by P. aeruginosa. In addition, CP treatment enhanced the ability of S. aureus to mount Fe-starvation responses and caused S. aureus to express host virulence genes. This analysis illuminated the physiological consequences of CP treatment that extend beyond metal starvation and impact interspecies interactions. Our findings provide a working model in which CP effectively disarms P. aeruginosa by inhibiting the production of anti-staphylococcal factors and boosts the ability of S. aureus to protect itself from attack.IMPORTANCEThe innate immune protein calprotectin (CP) defends the host against bacterial pathogens by sequestering multiple essential nutrient metal ions at infection sites. In addition to this role in nutritional immunity, CP promotes the survival of Staphylococcus aureus in coculture with Pseudomonas aeruginosa, an effect that is independent of its metal-sequestering function. In this work, we sought to understand how CP modulates this interspecies interaction by evaluating the transcriptional responses of P. aeruginosa and S. aureus to CP and metal limitation in cocultures. Our study revealed that CP attenuates the ability of P. aeruginosa to attack S. aureus with anti-staphylococcal factors and enhances the capacity of S. aureus to withstand this assault, effects that are not recapitulated by metal limitation. This work provides a new understanding of how CP modulates microbial interactions that are relevant to human health.

  • Research Article
  • 10.1016/j.taap.2025.117439
DNA damage response inhibition is an early event in cadmium-induced breast carcinogenesis.
  • Sep 1, 2025
  • Toxicology and applied pharmacology
  • Alexandra N Nail + 6 more

DNA damage response inhibition is an early event in cadmium-induced breast carcinogenesis.

  • Research Article
  • 10.3847/1538-4357/add2ee
Dust in the Smith Cloud? A UV Investigation into the Smith Cloud’s Gas-phase Abundance Patterns
  • Jul 29, 2025
  • The Astrophysical Journal
  • Johanna T Vázquez + 13 more

Abstract The Smith Cloud is a high-velocity cloud (HVC) on its final approach to the Milky Way that shows evidence of interaction with the Galaxy’s disk. We investigate the metallicity and gas-phase chemical depletion patterns in this HVC using UV absorption-line observations toward two background QSOs taken with the Hubble Space Telescope/Cosmic Origin Spectrograph and H i 21 cm emission-line observations taken with Green Bank Telescope. We find evidence of silicon gas-phase depletion with [Si/S] = − 0.7 2 − 0.26 + 0.24 and [Si/O]3σ ≲ −0.05, implying the presence of dust within the Smith Cloud. Because dust is galactic in origin, this HVC could trace the return leg of a Galactic fountain or a dwarf galaxy that passed through the Galactic plane.

  • Research Article
  • Cite Count Icon 1
  • 10.1128/jb.00181-25
Reductive activation of the disulfide-containing antibiotic thiolutin is mediated by both bacillithiol and FAD-dependent disulfide reductases
  • Jul 24, 2025
  • Journal of Bacteriology
  • Ahmed Gaballa + 2 more

Metal ions are universally essential for life and are required for critical enzymes throughout metabolism. Metalloenzymes rely on metal import and trafficking pathways for loading of the desired metal. Many microbes produce natural products that serve as metal chelators, both for their own nutrition and to serve as antimicrobials. In response to infection, our immune cells restrict bacterial growth by deploying proteins that chelate metal ions as part of nutritional immunity. Cells respond to metal depletion by the activation of pathways that prioritize metal delivery to the most essential enzymes. Dithiolopyrrolone (DTP) class natural products are prodrugs that are reduced in cells to generate a potent, dithiol-containing zinc chelator. Here, we identify the cellular reductants, bacillithiol and the FAD-dependent oxidoreductases TrxB and AhpF, that activate the DTP antibiotic thiolutin in Bacillus subtilis. Genetic studies reveal that loss of the Spx transcription factor also increases thiolutin resistance, consistent with the known role of Spx in transcriptional activation of thioredoxin reductase (trxB) and genes required for bacillithiol synthesis. Collectively, our results support a model in which several parallel pathways all contribute to the reductive activation of DTP class prodrugs in vivo.IMPORTANCEMetal ion chelators (metallophores) are deployed by microbes to obtain nutrient metals, sequester excess metals, and act as antimicrobials to inhibit the growth of other organisms. Dithiolopyrrolones (DTPs) are a class of natural products that inhibit bacterial growth by the intracellular chelation of zinc and iron, two metal ions essential for growth. Thiolutin, a model DTP antibiotic, is activated by reduction inside cells and selectively chelates intracellular metals. Here, we demonstrate that the activation of the thiolutin prodrug is mediated by several parallel pathways, which greatly reduces the ability of cells to evolve antibiotic resistance. Since DTP antibiotics appear to primarily target zinc enzymes, they provide a powerful tool for exploring how cells adapt to zinc deficiency.

  • Research Article
  • Cite Count Icon 1
  • 10.3847/2041-8213/ade2e5
Origins of Carbon Dust in a JWST-observed Primeval Galaxy at z ∼ 6.7
  • Jul 14, 2025
  • The Astrophysical Journal Letters
  • Ambra Nanni + 6 more

Abstract JADES-GS-z6-0, a high-redshift galaxy (z ∼ 6.7) recently observed as part of the James Webb Space Telescope Advanced Deep Extragalactic Survey (JADES), exhibits a distinct bump in its rest-frame ultraviolet (UV) spectrum indicative of a large quantity of hydrocarbon grains, a sign of rapid metal and dust enrichment in its interstellar medium (ISM). This galaxy serves as an ideal case for examining rapid dust formation processes in the early Universe. We investigated diverse dust production channels from a possible maximal formation redshift of z form ≈ 17, enabling dust contributions from asymptotic giant branch (AGB) stars over the longest possible timescale. Our model simultaneously reproduces key spectral features of JADES-GS-z6-0 such as its Balmer decrement, UV slope, and UV bump. The match is obtained by adopting a star formation history in which a burst at ∼600 Myr accounts for approximately 30% of the galaxy’s final stellar mass. Our findings indicate two pathways for the formation of hydrocarbon grains, such as polycyclic aromatic hydrocarbons (PAHs): (1) efficient dust accretion within the ISM, necessitating a low depletion of metals into dust grains from Type II supernovae (≈10%), or (2) dust production predominantly by Type II supernovae, requiring a high depletion fraction (≈73%) without dust accretion. We further demonstrate that PAHs are unlikely to originate solely from AGB stars or from shattering of large grains in the ISM. The evolution of the UV slope with redshift points to a complex and bursty star formation history for galaxies observed by JADES.

  • Research Article
  • Cite Count Icon 2
  • 10.1016/j.dib.2025.111666
Life cycle inventory dataset for energy production and storage technologies: Standardized metrics for environmental modeling
  • May 14, 2025
  • Data in Brief
  • Elena Rozzi + 2 more

Life cycle inventory dataset for energy production and storage technologies: Standardized metrics for environmental modeling

  • Research Article
  • Cite Count Icon 4
  • 10.1093/mtomcs/mfaf010
Pharmacokinetics of metal excretion following different doses of sodium EDTA infusion
  • Apr 21, 2025
  • Metallomics: Integrated Biometal Science
  • Kathrin Schilling + 7 more

Chelation therapy is a promising approach to mitigating health risks associated with toxic metal exposure, which contributes to cardiovascular disease, neurotoxicity, and other chronic conditions. disodium ethylene diamine tetraacetic acid (EDTA) is widely used, but its optimal dosing strategy remains unclear. This study evaluates the dose-dependent efficacy of EDTA in mobilizing toxic metals, including lead (Pb), cadmium (Cd), and gadolinium (Gd), while minimizing the loss of essential metals like copper (Cu) and manganese (Mn) to optimize therapeutic safety and efficacy. Ten volunteers (≥50 years) received 3 infusions at doses of 0.5, 1, and 3 g of EDTA over 30 min, 1 h, and 3 h, respectively. Urine and blood samples were analyzed pre- and post-infusion to assess pharmacokinetics of metal chelation. Urinary Pb excretion increased by 2200% at 0.5 g, with only a marginal gain at higher doses (3300%), supporting low-dose EDTA efficacy. Urinary Cd clearance required 3 g EDTA due to its strong tissue binding. Notably, Gd excretion increased by up to 78 000% even at 0.5 g EDTA, highlighting EDTA's potential to reduce long-term Gd burden post-MRI. Urinary excretion of essential metals varied, with Mn and Zn loss increasing at higher EDTA doses, underscoring the need for dose optimization while Cu and Ca only showed a clear increase urinary excretion at 3 g EDTA. Overall, a 0.5 g EDTA dose effectively mobilized Pb and Gd while minimizing essential metal depletion, reducing infusion time to 30 min, and improving patient compliance. These findings align with TACT and TACT 2 studies, reinforcing EDTA's long-term benefits in Pb reduction and supporting low-dose EDTA as a safe, efficient, and well-tolerated detoxification strategy.

  • Open Access Icon
  • Research Article
  • 10.1101/2025.04.14.648724
Calprotectin protects Staphylococcus aureus in coculture with Pseudomonas aeruginosa by attenuating quorum sensing and decreasing the production of pseudomonal antimicrobials
  • Apr 14, 2025
  • bioRxiv
  • Wei H Lee + 2 more

Pseudomonas aeruginosa and Staphylococcus aureus cause debilitating polymicrobial infections in diverse patient populations. Studies of these bacterial pathogens in coculture have shown that environmental variables including Fe availability and the host-defense protein calprotectin (CP) impact coculture dynamics. To decipher how CP modulates interactions between P. aeruginosa and S. aureus, we employed dual-species RNA-seq to examine the transcriptional responses of both pathogens in coculture to CP treatment and metal depletion. Analysis of these responses revealed that, for both P. aeruginosa and S. aureus, CP treatment not only induced gene expression changes consistent with single- and multi-metal starvation responses, but also induced gene expression changes that were not observed under metal limitation. For P. aeruginosa, CP treatment induced gene expression changes pointing to a shift in chorismate flux away from alkylquinolone and phenazine biosynthesis towards folate biosynthesis. These observations were consistent with decreased production of alkylquinolones by P. aeruginosa, including the potent anti-staphylococcal alkylquinolone N-oxides. CP treatment afforded perturbed levels of two quorum sensing molecules, 3-oxo-C12-homoserine lactone and C4-homoserine lactone, produced by P. aeruginosa. In addition, CP treatment enhanced the ability of S. aureus to mount Fe starvation responses and caused S. aureus to express host virulence genes. This analysis illuminated physiological consequences of CP treatment that extend beyond metal starvation and that these consequences impact interspecies interactions. Our findings provide a working model in which CP effectively disarms P. aeruginosa by inhibiting the production of anti-staphylococcal factors and boosts the ability of S. aureus to protect itself from attack.

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