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Among all the heavy metals, Pb, Cd, and As are the most harmful pollutants in the environment. They reach into the organisms via various levels of food chains i.e. air and water. Glutathione-s-transferase (GST, E.C. 2.5.1.18), a key enzyme of xenobiotics metabolism, plays an important role in the removal of several toxicants. The present study aimed to evaluate any inhibitory action of these heavy metals on the GST enzyme isolated from the hepatic tissues of rats. A 10 % (w/v) homogenate of rat liver was prepared in cold and centrifuged at 4 °C at 9000xg for 30 min. The supernatant was collected and kept frozen at -20 °C or used fresh for carrying out different experiments. The activity of GST was monitored spectrophotometrically at 340 nm using 220 µg of soluble protein with varying equal substrate concentrations (0.125-2 mM) in phosphate buffer (50 mM, pH 6.5). To assess the impact of heavy metals on the enzyme activity, different concentrations of Cd (0-0.6 mM) and Pb (0-2 mM) were added to the reaction mixture followed by monitoring the residual activity. The optimum temperature and pH of rat liver GST were found to be 37 °C and 6.5, respectively. The Km value for GST was 0.69 mM and the Vmax was found to be 78.67 U/mg. The Cd and Pb significantly altered the kinetic behaviour of the enzyme. The Vmax and Kcat/Km parameters of GST were recorded to be decreased after interaction with Cd and Pb individually and showed a mixed type of inhibition pattern suggesting that these inhibitors may have a greater binding affinity either for the free enzyme or the substrate-enzyme complex. These metals showed a time-dependent enzyme inhibition profile. Cd was found to be the most potent inhibitor when compared to other treated metals; the order of inhibitory effect of metal ions was Cd>Pb>As. The in silico ion docking analysis for determining the probable interactions of Cd and Pb with fragmented GST validated that Cd exhibited higher inhibition potential for the enzyme as compared to Pb. The results of the present study indicated that exposure of both the Cd and Pb may cause significant inhibition of hepatic GST; the former with higher inhibitory potential than the later. However, As proved to be least effective against the enzyme under the aforesaid experimental conditions.

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In aquaponic farming, there is a potential risk that heavy metals will contaminate the water, which can lead to heavy metal accumulation in the plants. Our research investigated the accumulation of mercury (Hg) and lead (Pb) under aquaponic conditions and the effect of their increased presence on the uptake of other macro- and micronutrients using watercress (Nasturtium officinale) as a model plant. The potential modifying effect of humic acid on heavy metal accumulation was also investigated. Adding Hg and Pb increased the mercury and lead levels of the watercress plants to over 300 µg kg-1, while the addition of humic acid significantly reduced the concentration of both mercury and lead in the plants compared to plants treated with heavy metals alone, from 310.647 µg kg-1 to 196.320 µg kg-1 for Hg and from 313.962 µg kg-1 to 203.508 µg kg-1 for Pb. For Fe and Mn, higher values were obtained for the Hg + humic acid treatments (188.13 mg kg-1 and 6423.92 µg kg-1, respectively) and for the Pb + humic acid treatments (198.26 mg kg-1 and 6454.31 µg kg-1, respectively). Conversely, the Na, K, Cu levels were lower compared to those in plants treated with heavy metals alone. Our results demonstrated that watercress can accumulate mercury, leading to high levels, even above food safety standards, highlighting the importance of water quality control in aquaponic systems. Furthermore, these results suggest that watercress could be used as a natural filter in recirculation systems. The addition of humic acid significantly reduced the accumulation of heavy metals and altered the element content in the plant.

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In this study, xCaO‧5Fe2O3‧(95-x)Pb glasses and vitroceramics containing various concentrations of calcium ions (from 0 to 50 mol% CaO) were prepared using the spent anodic plate of a car battery. X-ray diffraction analysis revealed changes in the network structure as a function of CaO content. The intensities of the IR bands due to the sulfate and sulfite units were lowered, indicating a decrease in the sulfurization degree within the lead network. In the UV-vis spectra, the presence of electronic transitions of the Fe3+, Pb2+, and Fe2+ ions were identified. The EPR spectra were characterized by resonance signals centered at about g ~ 2 and 4.3, corresponding to the trivalent iron ions. For the samples with 5 ≤ x ≤ 12, the signals decreased abruptly, suggesting a Fe3+→Fe2+ interconversion and the formation of the Fe3O4 crystalline phase. A considerable increase in the intensity of the signal centered around g ~ 2 was observed as the CaO concentration increased to 30% in the host matrix. Our results confirm that the higher CaO levels of 3 mol% are responsible for the increase in the radius of curvature of the semicircle arcs in the EIS plots and the decrease in their conductivity.

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Lead isotope analysis is the main method to trace the sources and cycling of Pb in the biosphere system. The linchpin of such application hinges on the assumption that there is no negligible or biologically mediated isotopic fractionation of Pb occurs in the environment. However, recent measurements by high-precision multi-collector mass spectrometry revealed that biological isotope fractionation of heavy mass elements is a prevalent phenomenon. This study shows that compared with the Pb sources, the maize plant (Zea mays L.) organs exhibit a wider range of Pb isotope compositions and a depletion of radioactive Pb isotopes (206Pb, 207Pb, and 208Pb). Moreover, three independent studies consistently indicate that the 206Pb/207Pb ratio of maize organs varies as root/leaf > stem/grain, reflecting a continuous loss of light Pb isotopes during transportation. The conventional wisdom fails to account for these phenomena, suggesting that maize may undergo Pb isotope fractionation during the absorption and transportation of Pb. However, compared with other non-traditional isotopes, Pb isotope exhibits a more significant fractionation magnitude. We tentatively attribute this fractionation to the Pb tolerance mechanism of maize and its selective absorption of various forms of Pb, which requires further research to validate. Findings from this study mandate caution in future Pb source trace in plants using Pb isotope methods and open up applications in using Pb isotopic fractionation to track Pb uptake and transfer pathways and decipher the associated detoxification mechanisms in plants.

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Environmental magnetism plays an important role in monitoring heavy metal pollution, but most studies are confined to indicating only the levels of heavy metals using magnetic parameters. This study established new magnetic proxies for accurately depicting the sources and bioavailability of heavy metals in contaminated soils. We observed different relationships between χ and SIRM in the soils contaminated by non-ferrous metal smelting compared to those polluted by coal combustion and steel smelting. Furthermore, we found that the soft magnetic components (IRMsoft) in the soils were mainly controlled by the non-ferrous metal smelting activities, while the hard magnetic components (HIRM) might be affected by the iron erosion. These new magnetic proxies enriched the source composition spectrum and improved the accuracy of the source apportionment analyses (principal component analysis and positive matrix factorization), yielding a result that was comparable to that by Pb isotope fingerprinting. We also found strong relationships between magnetic parameters (especially IRMsoft) and bioavailable fractions of heavy metals, indicating that magnetic measurement may be a powerful tool for monitoring the bioavailability of heavy metals. This study expands the application fields of magnetism in environmental science research.

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Soil heavy metal removal strategies are increasingly valued for effectively reducing contamination and preventing secondary pollution. In this work, a double network hydrogel (Fe2O3@LH), consisting of lignosulfonate (LS) and polyacrylamide with embedded Fe2O3 nanoparticles, was synthesized successfully via a one-pot method and subsequently applied to adsorb lead (Pb) from contaminated soil. Incorporating Fe2O3 into the hydrogel enhances the adsorption capacity of Fe2O3@LH for Pb(II). The Fe2O3@LH hydrogel demonstrates a maximum Pb(II) adsorption capacity of 143.11 mg g-1, with Pb(II) removal mechanisms involving electrostatic adsorption, cation exchange, precipitation reactions, and the formation of coordination complexes, achieving a 22.3 % maximum removal efficiency in soil cultivation experiments. Additionally, the application of Fe2O3@LH markedly reduces the concentrations of cadmium (Cd) and arsenic (As) in the soil, meanwhile enhances the levels of total nitrogen (TN), soil organic matter (SOM), and cation exchange capacity (CEC) by 23.1 %, 10.6 %, and 16.9 %, respectively. Following 90 days of continuous application in the soil, the recovery rate of Fe2O3@LH remains above 75 %. The toxicity assay using zebrafish larvae indicates that Fe2O3@LH demonstrates good biosafety. This study demonstrates the considerable potential of Fe2O3@LH hydrogel for practical application in reducing Pb(II) levels in contaminated soil.

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Influenza A virus, particularly the H5N1 strain, poses a significant threat to public health due to its ability to cause severe respiratory illness and its high mortality rate. Traditional antiviral drugs targeting influenza A virus have faced challenges such as drug resistance and limited efficacy. Therefore, new antiviral compounds are needed to be discovered and developed. This study concentrated on examining the stability and behavior of the H5N1 polymerase PB2 CAP-binding domain when interacting with natural compounds, aiming to identify potential candidates for antiviral drug discovery. Through the virtual screening process, four lead compounds, ZINC000096095464, ZINC000044404209, ZINC000001562130, and ZINC000059779788, were selected, and these compounds showed binding energies -9.6, -9.4, -9.3, and -9.2 kcal/mol, respectively. When complexed with PB2, the ligand showed acceptable binding stability due to significant bond formation. However, during the 200ns MD simulation analysis, three (ZINC000096095464, ZINC000044404209, and ZINC000059779788) showed significant stability, which was proven by the trajectory analysis. The Rg-RMSD-based FEL plot showed significant structural stability due to stable conformers. The free-binding energy calculation also validates the stability of these complexes. This study offers valuable insights into the stability and dynamics of the H5N1 polymerase PB2 CAP-binding domain in complexes with natural compounds. These findings highlight the potential of these natural compounds as antiviral agents against the H5N1 influenza virus. Furthermore, this research contributes to the broader field of influenza virus treatment by demonstrating the effectiveness of computational methods in predicting and evaluating the stability and dynamics of potential drug candidates.

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The study investigates the sources of metals in urban road dusts using elemental concentration and Pb isotopic ratios. The elemental concentrations are also utilized to determine the present heavy metal emissions as well as projected emissions till 2045. Bayesian mixing model for source apportionment highlights the significant contributions of both exhaust and non-exhaust sources to the metal-enriched urban road dusts, with each contributing approximately 40 %. Emission analysis reveals that India's projected electric vehicle (EV) penetration may not be sufficient to suppress the metal emissions from vehicular exhausts. Further challenge is posed by high metal concentrations in the non-exhaust sources, that dominates the emission of some metals compared to exhaust sources. If the metal concentrations remain unchanged, the emission analysis predicts alarming increases in total emissions from all the exhaust and non-exhaust sources by 174 %, 176 %, 163 % and 184 % for Ni, Cu, Zn and Pb, respectively, from 2022 to 2045. Thus, it is crucial to reduce the metal concentrations in traffic emission sources and also impose better regulatory measures to improve the urban metal pollution scenario.

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This study presents a computational investigation into the mechanistic pathway and the linker units involved in forming the zwitterionic 1,2-anti-addition product of non-conjugated diacetylenes, di(propargyl)ether (DPE), di(prop-2yn-1yl)sulfane (DPS) and 1,6-Heptadiyne (HD) catalyzed by the inter-molecular phosphine/borane frustrated Lewis pairs (FLPs), i.e., PPh2[C6H3(CF3)2](P-CF)/[B(C6F5)3]([B]) and P(o-tolyl)3(P-tol)/[B(C6F5)3]([B]). The potential energy surface (PES) calculations reveal that the anti-addition of P-CF to the internal C-atoms of acetylene units is energetically more favored than that of the addition of P-tol in DPE, DPS, and HD by ∼10.0, ∼9.2, and ∼6.0 kcal/mol, respectively. The calculations performed with DPE contain "-O-," linker unit exhibits superior reactivity than DPS and HD, which suggests the electronegativity of linkers plays a significant role and facilitates the addition of Lewis bases. The higher electronegativity of linker units enables the 1,2-addition reaction by lowering the free energy activation barriers, as observed in the DFT calculations. The Molecular Electrostatic Potential (MESP) study shows that the electrostatic interactions favor the addition of P-CF to the active acetylene positions (C5/C4/C4) of [B]-DPE/DPS/HD-π complexes than the P-tol. The Distortion/Interaction (D/I) analysis reveals that transition states involving P-CF (TS1, TS3, and TS5) exhibit more interaction energy (ΔEInt) and less distortion energies (ΔEd) than that of the P-tol (TS2, TS4, and TS6). Further, the Energy Decomposition Analysis (EDA) also rationalizes the preferential approach of the electron-deficient Lewis base over the electron-rich one on the basis of the significant contribution of orbital interaction energies (ΔEorbital) in the cases of P-CF; TS1, TS3, and TS5. This study suggests that the electronic effects of substrates and the FLPs are crucial to facilitate the desired products formed with non-conjugated terminal alkynes.

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Most Pb/Zn smelter contaminated sites in China are often encountered natural phenomenon known as freeze-thaw (F-T) cycles and acid rain. However, the coupled effects of F-T cycles and acidification on the release behavior of potentially toxic elements (PTEs) from soils remains unclear. A mechanistic study on PTEs release from soils was conducted by revealing the physicochemical weathering characteristics of minerals under F-T cycles combined with acidification. The results from F-T test indicated that among F-T parameters, F-T frequency were the more important factors influencing PTEs release, with the corresponding contribution ranges of 21.20-94.40 %. As pH decreased, the leaching concentrations of As, Cd, Cu, Mn, Pb and Zn did not increase under the same F-T frequency. As F-T frequency increased, the leaching concentrations of these studied PTEs also did not increase under the same pH condition. Microstructure characteristics revealed that the soils were a complex system with multi-mineral aggregates, which had experienced complex physicochemical weathering after F-T combined with acidification treatment. Combined with geochemical modeling results, PTEs release was found to be mainly influenced by the microstructure damage and proton corrosion of minerals, while little affected by their precipitation and dissolution. The mutual coupling relationships of mineral weathering and PTEs release were conducive to the better understanding of the migration behavior of PTEs in contaminated sites under complex environment scenarios. The present study results would provide theoretical instruction and technical support for the longevity evaluation of multi-metal stabilization remediation.

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Due to the exceedingly poisonous properties of Pb2+, it is imperative to conduct a thorough assessment of its quantity in both biological and environmental samples, as this is crucial for safeguarding public health. This study describes an economic turn-off fluorescent aptasensor for the quantitative analysis of Pb2+ employing 3,4,9,10-perylenetetracarboxylic acid diimide (PTCDI) as a cost-effective fluorophore, gold nanoparticles (AuNPs) as separating agent and an elongated aptamer as both targeting agent and PTCDI loading site. The fundamental principle of the suggested fluorescent aptasensor, which is based on PTCDI, relies on detecting variations in the fluorescence intensity of PTCDI when an elongated aptamer (as single-stranded DNA) is present or absent. The advanced aptasensor is advantageous due to the elongation of the lead aptamer sequence length induced by terminal deoxynucleotidyl transferase (TdT), resulting in enhanced sensitivity. The presence of Pb2+ and the centrifugation process causes the separation of the poly A-modified aptamer/Pb2+ conjugate from the poly T sequence. Hence, the interaction of PTCDI with the poly A moiety in the modified aptamer leads to a decrease in its fluorescence emission. The findings showcased that the fluorescent aptasensor exhibited exceptional specificity towards Pb2+ ions, while the biosensing platform accomplished an impressive detection limit of 3.7 pM. Moreover, the suggested aptasensor utilizing PTCDI exhibits a commendable capability in quantitatively analyzing Pb2+ within human serum samples and mineral water.

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Soil Pb contamination is inevitable, as a result of phosphate mining. It is essential to explore more effective Pb remediation approaches in phosphate mining wasteland soil to ensure their viability for a gradual return of soil quality for cultivation. In this study, a Pb-resistant urease-producing bacterium, Serratia marcescens W1Z1, was screened for remediation using microbially induced carbonate precipitation (MICP). Magnesium polypeptide (MP) was prepared from soybean meal residue, and the combined remediation of Pb contamination with MP and MICP in phosphate mining wasteland soil was studied. Remediation of Pb using a combination of MP with MICP strain W1Z1 (WM treatment) was the most effective, with the least exchangeable Pb at 30.37% and the most carbonate-bound Pb at 40.82%, compared to the other treatments, with a pH increase of 8.38. According to the community analysis, MP moderated the damage to microbial abundance and diversity caused by MICP. Total nitrogen (TN) was positively correlated with Firmicutes, pH, and carbonate-bound Pb. Serratia inoculated with strain W1Z1 were positively correlated with bacteria belonging to the Firmicutes phylum and negatively correlated with bacteria belonging to Proteobacteria. The available phosphate (AP) in the phosphate mining wasteland soil could encapsulate the precipitated Pb by ion exchange with carbonate, making it more stable. Combined MP-MICP remediation of Pb contamination in phosphate mining wasteland soil was effective and improved the soil microenvironment.

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The escalating contamination caused by lead ions (Pb2⁺) and its harmful effects on all life forms has raised global concerns. Certain microalgae thrive in metal mining sites characterized by low pH and high concentrations of Pb2⁺, which are usually prohibitive for many microorganisms. Little is known about the mechanisms underlying the adaptation of such microalgae to these hostile conditions. In this study, we elucidated the adaptive strategies of the green microalga Micractinium belenophorum strain AUMW, isolated from a lead mining site, and its application for the removal of Pb+2. Results revealed that strain AUMW can efficiently tolerate up to 200 ppm of Pb+2 in an F/2 medium. Further experimental variables were optimized through response surface methodology (RSM), and 99.6 % removal of Pb2⁺ was achieved. Novel adaptive responses of strain AUMW to high levels of Pb2⁺ include: (i) activation of metal-protective response by modulation of quantum yield (F v /F m ) and non-photochemical quenching (NPQ) of photosystem II; (ii) extracellular silicification encapsulated cells of strain AUMW and altered cell morphology from oval to hexagonal; (iii) silicification prevented intracellular translocation of Pb+2; (iv) silicification boosted adsorption of Pb+2, thus enhanced its removal. This study offers new insights into the protective role of silicification in green microalgae and its potential for the removal of metals from metal-polluted sites, waste from energy storage battery industries, and spent batteries. It also provides a solid base to explore the genetic and metabolic pathways involved in the adaptation of strain AUMW to elevated levels of Pb+2.

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Titanite-bearing calc-silicates and mafic gneisses, metamorphosed under amphibolite- to granulite-facies conditions, crop out in Val d'Ossola area (Ivrea-Verbano Zone, Italy). The Ivrea-Verbano Zone represents an exhumed section of the pre-Alpine middle to lower continental crust which escaped the Alpine subduction, thus provides a unique opportunity to study continental crustal processes and evolution. Among several samples, three, collected from different locations, were chosen for detailed analyses of titanite. Petrochronology of titanite was performed with Laser ablation split-stream (LASS) technique on petrographic thin sections. Petrochronological results on titanite do not define clear correlations with chemistry except for one sample. Rare earth elements (REE) patterns of titanite from the three samples are apparently different in terms of average concentration (i.e., lower or upper 1000 times CI), shapes and occurrence or absence of Eu negative anomaly. Al/Fe vs ΣLREE and Fe content vs Zr/Y plots show that the studied samples coincide with metamorphic rock field deriving from calc-silicates and mafic protoliths, as previously demonstrated in literature. Any compilations of petrochronological data on titanite from the metamorphic volcano-sedimentary sequence of Val d'Ossola can be found in literature. Therefore, these data represent a new insight on an accessory mineral phase whose significance and scientific interest are rising in the last years. Future studies of the evolution of these kinds of rock, widespread in the high-grade metamorphic basements, will benefit from these data as a term of comparison.

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KEY MESSAGE: Cd induces photosynthetic inhibition and oxidative stress damage in H. citrina, which mobilizes the antioxidant system and regulates the expression of corresponding genes to adapt to Cd and Pb stress. Cd and Pb are heavy metals that cause severe pollution and are highly hazardous to organisms. Physiological measurements and transcriptomic analysis were combined to investigate the effect of 5 mM Cd or Pb on Hemerocallis citrina Baroni. Cd significantly inhibited H. citrina growth, while Pb had a minimal impact. Both Cd and Pb suppressed the expression levels of key chlorophyll synthesis genes, resulting in decreased chlorophyll content. At the same time, Cd accelerated chlorophyll degradation. It reduced the maximum photochemical efficiency of photosystem (PS) II, damaging the oxygen-evolving complex and leading to thylakoid dissociation. In contrast, no such phenomena were observed under Pb stress. Cd also inhibited the Calvin cycle by down-regulating the expression of Rubisco and SBPase genes, ultimately disrupting the photosynthetic process. Cd impacted the light reaction processes by damaging the antenna proteins, PS II and PS I activities, and electron transfer rate, while the impact of Pb was weaker. Cd significantly increased reactive oxygen species and malondialdehyde accumulation, and inhibited the activities of antioxidant enzymes and the expression levels of the corresponding genes. However, H. citrina adapted to Pb stress by the recruitment of antioxidant enzymes and the up-regulation of their corresponding genes. In summary, Cd and Pb inhibited chlorophyll synthesis and hindered the light capture and electron transfer processes, with Cd exerting great toxicity than Pb. These results elucidate the physiological and molecular mechanisms by which H. citrina responds to Cd and Pb stress and provide a solid basis for the potential utilization of H. citrina in the greening of heavy metal-polluted lands.

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Anthropogenic activity has disturbed the natural distribution and circulation of trace elements in the environment. This has led to increased background levels of numerous elements, causing global pollution. In this context, seabirds are relevant bioindicators of environmental contamination. This study focuses on the ecological factors that influence the concentrations of 14 trace elements in the blood of the chicks of three sympatric gull species from the French coast of the English Channel. Between 2015 and 2017, 174 birds were sampled in the industrialised Seine Estuary (in the city of Le Havre and on Ratier Island) and in the remote Chausey Islands, 200 km to the west. We also considered the Se:Hg molar ratio using Hg concentrations in those birds. Ag and V concentrations were below the quantification limit in all cases, while the fraction of non-quantified samples was higher than 30 % for Cd, Cr and Ni. Among the elements quantified in the samples, the lowest concentrations were noted for Co and the highest for Fe, building the following order: Co < Cd < Ni < Mn ≤ Pb < Cr < Hg < Cu < Se < As < Zn < Fe. No unanimous scheme of concentrations among elements, species and sites existed. Similarly, different models were fitted and different factors were significant for different species and elements. We observed the biomagnification of As and the biodilution of Pb. Pb concentrations were also highest in the industrial site in the city of Le Havre. Despite the high proportion of non-quantified samples for Cd, Cr and Ni, we continued to notice higher concentrations in the marine environment of the Chausey Islands. Concentrations of some elements clearly revealed habitat dependence. In some cases the Se:Hg molar ratio was lower than 4, a threshold for diminishing Hg toxicity by Se.

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Soil salinization and heavy metal pollution in the Yellow River Delta region have elicited increasing concern. Therefore, revealing the underlying mechanism of the impact of soil salinity on potential toxic elements (PTEs) is crucial for environmental protection and the rational utilization of resources in this area. In this study, we employed CatBoost-SHAP and multiscale geographically weighted regression (MGWR) models to comprehensively investigate the spatial effects of soil electrical conductivity (EC1:5) on PTEs. Additionally, we employed a space-for-time substitution strategy with the aim of investigating how increasing soil salinity, represented by EC1:5, K+, Na+, Ca2+, and Mg2+, affects the bioavailability of PTEs over time. The primary findings are as follows: (1) for most PTEs, the influence of soil EC1:5 on the bioavailable forms of these elements surpassed its impact on their total concentrations. (2) The results of the MGWR model indicated that exchangeable Ca (aCa) in the soils of the eastern coastal areas markedly increased the bioavailable Cd (aCd), bioavailable Cu (aCu), and bioavailable Zn (aZn). (3) When the soil EC1:5 ranges between 2 and 6 dS/m, exchangeable Na (aNa) primarily competed for the adsorption sites of bioavailable Pb (aPb). However, as the soil EC1:5 increases to 6-10 dS/m, exchangeable Mg (aMg) and aCa became the primary competing ions, with aMg playing a more significant role than aCa. These findings provide valuable theoretical insights and practical guidance for saline-alkali soil improvement and PTEs pollution control in the Yellow River Delta region, thereby providing a foundation for sustainable environmental management and resource utilization.

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The association between metal mixtures and kidney function has been reported. However, reports on the mechanism of metal toxicity were limited. Oxidative stress was reported as a possible cause. This study aimed to determine the association between of kidney function and metals, such as arsenic (As), cadmium (Cd), cobalt (Co), copper (Cu), lead (Pb), selenium (Se), and zinc (Zn), and to explore the possible mediating role of tumor necrosis factor alpha (TNF-α) between metal toxicity and kidney function. In this study, we recruited 421 adults from a health examination. The concentration of blood metals was analyzed using inductively coupled plasma mass spectrometry. We used linear regression models to assess the association between metals and TNF-α. Then, mediation analysis was applied to investigate the relationship between metal exposure, TNF-α, and kidney function. In univariate linear regression, blood As, Cd, Co, Cu, Pb, and Zn levels significantly increased TNF-α and decreased kidney function. Higher blood As and Pb levels significantly increased TNF-α in multivariable linear regressions after adjusting for covariates. We found that blood levels of As (coefficients = -0.021, p = 0.011), Pb (coefficients = -0.060, p < 0.001), and Zn (coefficients = -0.230, p < 0.001) showed a significant negative association with eGFR in the multiple-metal model. Furthermore, mediation analysis showed that TNF-α mediated 41.7 %, 38.8 %, and 20.8 % of blood Cd, As and Pb, respectively. Among the essential elements, TNF-α mediated 24.5 %, 21.5 % and 19.9 % in the effects of blood Co, Cu, and Zn on kidney function, respectively. TNF-α, acting as a mediator, accounted for 20.1 % of the contribution between the WQS score of metal mixtures and the eGFR (p < 0.001). This study suggested that TNF-α may be a persuasive pathway mediating the association between metals and kidney function. Inflammation and kidney injury could be the underlying mechanisms of metal exposure. However, there is still a need to clarify the biochemical mechanism in follow-up studies.

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Lake Naivasha, Kenya's second-largest freshwater body is a wetland of international ecological importance and currently subjected to unprecedented anthropogenic influence. The study aims to chronologically reconstruct the main human activities and background weathering reactions that govern metal mobilizations into the lake and their potentially adverse effects on its ecological status. We combine extensive geochemical analyses (major, trace elements, Zn-Pb isotope ratios) in a dated lake sediment record and catchment rocks with remote sensing techniques. Downcore geochemical variations reflect natural ecosystem destabilizations occurring as early as the first half of the 20th century. These coincide with changes towards less radiogenic Pb-isotope values which persist towards the top of the core (206Pb/207Pb = 1.243 at core base ∼1843, to 206Pb/207Pb = 1.225 at ∼1978). We interpret the land-clearance for agricultural purposes on the Aberdare Range and documented early aviation activities as possible vectors of this early Pb-isotope excursion. The overlapping Pb-isotope signatures between sediment sources and anthropogenic contributions challenges a straightforward deconvolution of the two. Our conservative model calculations suggest, nevertheless, that an addition of up to ∼1.8 % Pb-gasoline influx to the total Pb flux, peaking in the 1980s is able to explain the Pb distribution trend. Homogeneous Zn-isotope compositions in sediments deposited until ∼1970s (δ66/64Zn = 0.216-0.225 ‰) do not follow major hydro-climatic events or anthropogenic forcing but likely reflect lake-specific natural cycling. Subsequent higher variations to both heavier (up to δ66/64Zn = 0.242 ± 0.005 ‰) and lighter (down to δ66/64Zn = 0.184 ± 0.003 ‰) Zn-isotope values are contemporaneous with intensification of large-scale horticultural industry in the catchment. Together with supporting indicators, the lighter Zn-isotope compositions in youngest analysed sediments (21st century) are attributable to increased biological productivity (algal blooms) and ongoing lake eutrophication. Our study demonstrates the applicability of the heavy metal isotope tool to reconstruct human influences on lake environments with complex geological settings such as the East African Rift System.

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Background: The non-viral production of CAR-T cells through electroporation of transposon DNA plasmids is an alternative approach to lentiviral/retroviral methods. This method is particularly suitable for early-phase clinical trials involving novel types of CAR-T cells. The primary disadvantage of non-viral methods is the lower production efficiency compared to viral-based methods, which becomes a limiting factor for CAR-T production, especially in chemotherapy-pretreated lymphopenic patients. Methods: We describe a good manufacturing practice (GMP)-compliant protocol for producing CD19 and CD123-specific CAR-T cells based on the electroporation of transposon vectors. The lymphocytes were purified from the blood of patients undergoing chemotherapy for B-NHL or AML and were electroporated with piggyBac transposon encoding CAR19 or CAR123, respectively. Electroporated cells were then polyclonally activated by anti-CD3/CD28 antibodies and a combination of cytokines (IL-4, IL-7, IL-21). The expansion was carried out in the presence of irradiated allogeneic blood-derived mononuclear cells (i.e., the feeder) for up to 21 days. Results: Expansion in the presence of the feeder enhanced CAR-T production yield (4.5-fold in CAR19 and 9.3-fold in CAR123). Detailed flow-cytometric analysis revealed the persistence of early-memory CAR-T cells and a low vector-copy number after production in the presence of the feeder, with no negative impact on the cytotoxicity of feeder-produced CAR19 and CAR123 T cells. Furthermore, large-scale manufacturing of CAR19 carried out under GMP conditions using PBMCs obtained from B-NHL patients (starting number=200x10e6 cells) enabled the production of >50x10e6 CAR19 in 7 out of 8 cases in the presence of the feeder while only in 2 out of 8 cases without the feeder. Conclusions: The described approach enables GMP-compatible production of sufficient numbers of CAR19 and CAR123 T cells for clinical application and provides the basis for non-viral manufacturing of novel experimental CAR-T cells that can be tested in early-phase clinical trials. This manufacturing approach can complement and advance novel experimental immunotherapeutic strategies against human hematologic malignancies.

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