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Increasing industrial activity causes the release of chemical compounds into aquatic habitats, including toxic heavy metals like cadmium and medications like ketoprofen, posing considerable ecological concerns. Although previous studies have shown that cadmium and ketoprofen individually cause cognitive impairment, there is a lack of information on the combined neurological effects of the two substances. We investigated the neurological consequences of persistent cadmium exposure in the presence of ketoprofen on adult zebrafish, providing an essential model for understanding cumulative impacts on vertebrate organisms. Behavioral assessments, bioaccumulation rates, biochemical studies, and histopathological exams were conducted over 42 days in authentic environmental settings. The results of our study show that cadmium (10 µg/L) and ketoprofen (10 and 100 µg/L) at environmentally relevant concentrations had a significant impact on locomotor activity, social interactions, and cognitive responses, indicating cumulative neurotoxicity in co-exposure groups compared to single pollutant groups. Biochemical tests show disturbances in antioxidant defense systems, while histological examinations reveal structural changes in zebrafish brain regions. Ketoprofen influences cadmium accumulation in the brain, underscoring the importance of conducting complete evaluations to understand the intricate interactions between environmental pollutants. This study improves our understanding of the complex interactions between heavy metals and medications, stressing the need to consider combined exposure when assessing the neurological effects on vertebrate models., (© 2024 Wiley Periodicals LLC.)

Cadmium (Cd) poses a significant threat to human health. However, chronic toxicity parameters for inhalation exposure are lacking, especially for noncritical systemic toxic effects. A physiologically based toxicokinetic (PBTK) model can be used to extrapolate toxicity parameters across various exposure routes. We combined a PBTK model with a human respiratory tract (HRT) model, which is applicable to the general population and capable of simulating the deposition and clearance processes of various airborne Cd compounds in the respiratory tract. Monte Carlo analysis was used to simulate the distribution of sensitive parameters to reflect individual variability. Validation based on datasets from general and occupational populations showed that the improved model had acceptable or better predictive performance, outperforming the original model with a 14.45 % decrease in the root mean square error (RMSE). Using this PBTK-HRT model, we extrapolated toxicity parameters from oral exposure to inhalation exposure for four systemic toxic effects with doseresponse relationships but no known inhalation toxicity parameters, and ultimately recommended reference concentrations (RfCs) for four diseases (chronic kidney disease: 0.01 μg/m 3 , osteoporosis: 0.01 μg/m 3 , stroke: 0.04 μg/m 3 , diabetes mellitus: 0.13 μg/m 3 ), contributing to a comprehensive assessment of the health risks of Cd inhalation exposure. ENVIRONMENTAL IMPLICATION: Cadmium (Cd), a heavy metal, can cause lung cancer, chronic kidney disease, and osteoporosis and pose a significant threat to human health. We combined a physiologically based toxicokinetic (PBTK) model with a human respiratory tract (HRT) model to achieve better predictive performance and wider applicability; this model was subsequently employed for route-to-route extrapolation of toxicity parameters. Additionally, for the first time, we focused on multiple subchronic and chronic systemic toxic effects in addition to critical effects and derived their reference concentrations (RfCs), which can be used to assess the health risk of Cd inhalation exposure more comprehensively and accurately., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Bivalves are often employed for biomonitoring contaminants in marine environments; however, in these large-scale programs, unavoidably, using multiple species presents a significant challenge. Interspecies differences in contaminant bioaccumulation can complicate data interpretation, and direct comparisons among species may result in misleading conclusions. Here, we propose a robust framework based on toxicokinetic measurements that accounts for interspecies differences in bioaccumulation. Specifically, via a recently developed double stable isotope tracer technique, we determined the toxicokinetics of cadmium (Cd)─a metal known for its high concentrations in bivalves and significant interspecies bioaccumulation variability─in six widespread bivalve species including mussels ( Perna viridis , Mytilus unguiculatus , Mytilus galloprovincialis ) and oysters ( Magallana gigas , Magallana hongkongensis , Magallana angulata ). Results show that oysters generally have higher Cd uptake rate constants ( k u : 1.18-3.09 L g -1 d -1 ) and lower elimination rate constants ( k e : 0.008-0.017 d -1 ) than mussels ( k u : 0.21-0.64 L g -1 d -1 ; k e : 0.018-0.037 d -1 ). The interspecies differences in tissue Cd concentrations are predominantly due to Cd uptake rather than elimination. Utilizing toxicokinetic parameters to back-calculate Cd concentrations in seawater, we found that the ranking of Cd contamination levels at the six sites markedly differs from those based on tissue Cd concentrations. We propose that this approach will be useful for interpreting data from past and future biomonitoring programs.

Despite the great interest in the consequences of global change stressors on marine organisms, their interactive effects on cadmium (Cd) bioaccumulation/biotoxicity are very poorly explored, particularly in combination with the toxicokinetic model and molecular mechanism. According to the projections for 2100, this study investigated the impact of elevated pCO 2 and increased temperature (isolated or joint) on Cd uptake dynamics and transcriptomic response in the marine copepod Tigriopus japonicus. Toxicokinetic results showed significantly higher Cd uptake in copepods under increased temperature and its combination with elevated pCO 2 relative to the ambient condition, linking to enhanced Cd bioaccumulation. Transcriptome analysis revealed that, under increased temperature and its combination with elevated pCO 2 , up-regulated expression of Cd uptake-related genes but down-regulation of Cd exclusion-related genes might cause increased cellular Cd level, which not only activated detoxification and stress response but also induced oxidative stress and concomitant apoptosis, demonstrating aggravated Cd biotoxicity. However, these were less pronouncedly affected by elevated pCO 2 exposure. Therefore, temperature seems to be a primary factor in increasing Cd accumulation and its toxicity in the future ocean. Our findings suggest that we should refocus the interactive effects between climate change stressors and Cd pollution, especially considering temperature as a dominant driver., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Toxic heavy metals pollution in urban soil has become a major global issue due to its adverse effects on the environment and human health. In this paper, 26 soil samples were analyzed to assess the speciation, bioavailability and human health risk of Arsenic (As), Mercury (Hg), Lead (Pb) and Cadmium (Cd) in urban soils of a heavy industrial city in NE China by using a Monte Carlo simulation approach. The results showed that As, Hg, Pb and Cd concentrations in the soil all exceed the corresponding background value of study area. Mercury displays the highest value of geo-accumulation index (Igeo), followed by Cd, Pb and As. The pollution load index (PLI) value (>2) indicates a moderate pollution level in the study area. The chemical speciation of HMs mainly exists in residual fraction except Cd. The probabilistic health risk assessment demonstrated that the mean values of Total Carcinogenic Risk (TCR) and Hazard Index (HI) calculated with total concentration are at the unacceptable level, with a higher risk to children than adults. However, the mean values calculated with bioavailable fraction are all within the acceptable level. The mean value of TCR and HI obtained by bioavailable fraction is about 96% and 95% lower than that obtained by total concentration, respectively. Thus, this study suggested that the bioavailable fraction of HMs is a more reliable parameter for health risk assessment, while the total concentration of HMs can overestimate the true risk. The results of this study provide some insight into the speciation, bioavailability and health risks of toxic heavy metals in urban soils in those heavy industrial cities., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In this study, we investigated the influence of temperature on the bioaccumulation and depuration of Crassostrea gigas exposed to Cd associated with its molecular responses. Oysters were acclimatized to different temperatures (10 °C, 15 °C, 20 °C, 25 °C, and 30 °C) for 14 d and then exposed to 10 μg/L Cd for 28 d, followed by a depuration period of 35 d. Oysters were sampled for chemical analysis by inductively coupled plasma mass spectrometry (ICP-MS) and for mRNA quantification by qPCR. In the digestive gland, gill, and mantle, the cadmium concentration at 10 °C was significantly lower than that at 25 °C and 30 °C in both the whole experiments. The use of a two-compartment model showed that the uptake rate k 1 in the above three tissues increased with increasing temperatures ranging from 15 to 25 °C. The fastest elimination rates and shortest half-lives were observed at 15-25 °C. The induction of metallothionein (MT) only occurred in the digestive gland at 15 °C and 20 °C at the end of the accumulation phase. In the mantle and gills, the expression of P-glycoprotein (P-gp) was significantly induced at the end of the accumulation phase and significantly inhibited at the end of the depuration phase. In the digestive gland, the expression of P-gp was induced at the end of both the accumulation and depuration phases. Heat shock protein (hsp70) expression exhibited an overall increasing trend throughout the experiment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In natural environment, the existence of interactions of toxic mixtures could induce diverse biochemical pathways and consequently exert different toxicological responses in aquatic organisms. However, little information is available on the effects of combined xenobiotics on lower aquatic invertebrates. Here, we assessed the effects of cadmium (Cd, 0.31 mg/L) as well as the mixture of Cd (0.31 mg/L) and benzo(a)pyrene (Bap, 5 or 50 μg/L) on bioaccumulation, antioxidant, lipid peroxidation (LPO) and metallothionein (MT) responses in gills of thick shell mussel Mytilus coruscus. Upon exposed to single Cd, the metal bioaccumulation, antioxidant enzymes activities, LPO and MT level significantly increased in the gills, suggesting an apparent toxicity to mussels. The interaction of Cd + 5 μg/L Bap did not significantly alter these endpoints compared to single Cd. However, once the dose of Bap elevated to 50 μg/L, the induction of bioaccumulation, antioxidant system and LPO was even more pronounced while the induction of MT was remarkably inhibited, implying an accentuated toxicity. Collectively, the current results demonstrated that 0.31 mg/L Cd exposure resulted in severe toxicity to mussels despite of the induction of MT system to alleviate the metal toxicity. Once the Cd exposure combined with Bap, the lower dose of Bap could not change the Cd toxicity while the higher dose of Bap accentuated the toxicity by inhibiting metallothionein synthesis. These findings might provide some useful clues for elucidation the mechanism of the interaction of combined xenobiotics in molluscs., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The present study investigated the protective effect of methanolic leaf extract of Morinda tinctoria. Roxb (MEMT) (200 mg/kg) via feed in supplementation with standard compound silymarin (400 mg/kg). M. tinctoria (Roxb.) belonging to Rubiaceae, is an evergreen shrub indigenous to unfarmed lands of tropical countries. It is considered as an essential traditional medicine attributing for the potential antioxidant and anti-inflammatory properties. The enhancements of antioxidant and antigenotoxic status in different tissues of cadmium (Cd) intoxicated Pangasius sutchi were evaluated by using various antioxidant assays (superoxide dismutase (SOD) and catalase (CAT) and lipid peroxidation) in addition to micronuclei (MN), binuclei (BN) and comet assay. The cadmium toxicated fish showed a significant (p < 0.001) increase in lipid peroxidation (LPO) activities in liver, gills, muscle and kidney whereas significant (p < 0.001) decline were observed in superoxide dismutase (SOD) and catalase (CAT) contents in all fish tissues. The results also revealed that, Cd exposure induced the formation of genotoxic endpoints like MN, BN, notched nuclei, kidney shaped nuclei and DNA damage in the fish erythrocytes. Maximum of 26.8% MN frequencies and maximum of 66.74% tail DNA damage were observed on the 7th day of Cd exposure. A time-dependent significant increase (p < 0.001) in the frequencies of MN, BN and tail DNA damage were observed in all treated groups against the control which started to decline from 14th day onwards. There was a decline in the LPO content, frequencies of MN, BN and percentage of tail DNA in contrast to significant elevation in SOD and CAT content in all tissues due to the combined treatment of M. tinctoria feed and water borne Cd exposure. It can be concluded from our observations that, supplementation of M. tinctoria leaf extract through feed alone produced enhanced antioxidant and antigenotoxic status in cadmium treated fish by diminishing oxidative stress and genotoxicity effects in a time dependent manner., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Metallothionein (MT) plays an important role in protecting organisms from the adverse effects of Cd, Hg, Zn and Cu. Investigations on mammals show variations in metallothionein concentrations and inducibility with age. This has never been investigated in invertebrates, and we determined the concentrations and inducibility of metallothionein in gills and midgut gland of different size classes of shore crabs from uncontaminated areas. Metallothionein concentrations in gills and midgut gland ranged between 30 and 40 μg g -1 dry weight with no differences among the different size classes. Concentrations of cadmium, copper and zinc in the midgut gland increased with increasing size of the crabs when the concentrations were expressed on a dry weight basis; water content in the midgut gland increased with the size and only the cadmium concentration increased with size when concentrations were expressed on wet weight basis. There was an inverse relationship between metallothionein and both copper and cadmium concentrations. Smaller crabs exposed to 1 mg Cd L -1 accumulated higher concentrations of cadmium in midgut gland and gills than larger ones and metallothionein concentrations in the midgut gland were higher in the smaller crabs. However, the increase in metallothionein concentration per accumulated unit of cadmium showed a linear increase with the size of the crabs. The ratio [Cd] midgut /[Cd] gills decreased with the size of the crabs. The overall conclusion is that baseline metallothionein concentrations do not change with age in shore crabs, but that the inducibility of metallothionein upon cadmium challenge does., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

To improve our understanding of underlying toxic mechanisms, it is important to evaluate differences in effects that a variety of metals exert at concentrations representing the same toxic level to the organism. Therefore, the main goal of the present study was to compare the effects of waterborne copper (Cu(II)), zinc (Zn(II)) and cadmium (Cd (II)) on a freshwater fish, the common carp (Cyprinus carpio), at concentrations being 0%, 25%, 50% and 100% of the 96 h LC50 (the concentration which is lethal to 50% of the population in 96 h). All the exposures were performed for a period of 1 week at 20°C. Our results show a rapid increase in the amount of copper and cadmium accumulated in the gills, while zinc only started to increase by the end of the experiment. All three metal ions increased metallothionein gene expression in both gills and liver. However, clear adverse effects were mainly observed for the Cu exposed group. Cu caused a decrease in Na level in gill tissue; it altered the expression of genes involved in ionoregulation such as Na + /K + -ATPase and H + -ATPase as well as the expression of oxidative stress-related genes, such as catalase, glutathione reductase and glutathione S-transferase. Zinc and cadmium exposure did not alter the ion levels in the gills. In addition, no obvious effect of oxidative stress was observed, except for a transient increase in glutathione reductase at the highest cadmium concentration., (© 2020 John Wiley & Sons, Ltd.)

Exposure to the environmental pollutant cadmium is ubiquitous, as it is present in cigarette smoke and the food supply. Over time, cadmium enters and accumulates in the kidneys, where it causes tubular injury. The breast cancer resistance protein (BCRP, ATP-Binding Cassette G2 ABCG2 ) is an efflux transporter that mediates the urinary secretion of pharmaceuticals and toxins. The ABCG2 genetic variant Q141K exhibits altered membrane trafficking that results in reduced efflux of BCRP substrates. Here, we sought to 1) evaluate the in vitro and in vivo ability of BCRP to transport cadmium and protect kidney cells from toxicity and 2) determine whether this protection is impaired by the Q141K variant. Cadmium concentrations, cellular stress, and toxicity were quantified in human embryonic kidney 293 cells expressing an empty vector (EV), BCRP wild-type (WT), or variant (Q141K) gene. Treatment with CdCl 2 resulted in greater accumulation of cadmium and apoptosis in EV cells relative to WT cells. Exposure to CdCl 2 induced expression of stress-related genes and proteins including MT-1A/MT-2A, NAD(P)H quinone dehydrogenase 1, and heme oxygenase-1 to a higher extent in EV cells compared with WT cells. Notably, the Q141K variant protected against CdCl 2 -induced activation of stress genes and cytotoxicity, but this protection was to a lesser magnitude than observed with WT BCRP. Lastly, concentrations of cadmium in the kidneys of Bcrp knockout mice were 40% higher than in WT mice, confirming that cadmium is an in vivo substrate of BCRP. In conclusion, BCRP prevents the accumulation of cadmium and protects against toxicity, a response that is impaired by the Q141K variant. SIGNIFICANCE STATEMENT: The breast cancer resistance protein transporter lowers cellular accumulation of the toxic heavy metal cadmium. This protective function is partially attenuated by the Q141K genetic variant in the ABCG2 gene., (Copyright © 2021 by The American Society for Pharmacology and Experimental Therapeutics.)

In this study, the intestinal permeability of metal(loid)s (MLs) such as arsenic (As), cadmium (Cd), lead (Pb) and mercury (Hg) was examined, as influenced by gut microbes and chelating agents using an in vitro gastrointestinal/Caco-2 cell intestinal epithelium model. The results showed that in the presence of gut microbes or chelating agents, there was a significant decrease in the permeability of MLs (As-7.5%, Cd-6.3%, Pb-7.9% and Hg-8.2%) as measured by apparent permeability coefficient value (P app ), with differences in ML retention and complexation amongst the chelants and the gut microbes. The decrease in ML permeability varied amongst the MLs. Chelating agents reduce intestinal absorption of MLs by forming complexes thereby making them less permeable. In the case of gut bacteria, the decrease in the intestinal permeability of MLs may be associated to a direct protection of the intestinal barrier against the MLs or indirect intestinal ML sequestration by the gut bacteria through adsorption on bacterial surface. Thus, both gut microbes and chelating agents can be used to decrease the intestinal permeability of MLs, thereby mitigating their toxicity., (© 2021. The Author(s).)

Cadmium (Cd) is a potential pathogenic factor in the nervous system associated with various neurodegenerative disorders. Puerarin (Pur) is an isoflavone purified from the Chinese medical herb, kudzu root, and exhibits antioxidant and antiapoptotic properties in the brain. In this study, the detailed mechanisms underlying the neuroprotective potential of Pur against Cd-induced neuronal injury was evaluated for the first time in vivo in a rat model and in vitro using primary rat cerebral cortical neurons. The results of the in vivo experiments showed that Pur ameliorated Cd-induced neuronal injury, reduced Cd levels in the cerebral cortices, and stimulated Cd excretion in Cd-treated rats. We also observed that the administration of Pur rescued Cd-induced oxidative stress, and attenuated Cd-induced apoptosis by concomitantly suppressing both the Fas/FasL and mitochondrial pathways in the cerebral cortical neurons of rats both in vivo and in vitro. Our results demonstrate that Pur exerted its neuroprotective effects by stimulating Cd excretion, ameliorating Cd-induced oxidative stress and apoptosis in rat cerebral cortical neurons.

Cadmium (Cd) is highly toxic to living organisms and the contamination of Cd in paddy soil in China has received much attention. In the present study, by conducting pot experiment, the influence of S fertilizer (S 0 ) on rice growth, iron plaque formation, Cd accumulation in rice plants and bacterial community in rice rhizosphere soil was investigated. The biomass of rice plants was significantly increased by S 0 addition (19.5-73.6%). The addition of S 0 increased the formation of iron plaque by 24.3-45.8%, meanwhile the amount of Cd sequestered on iron plaque increased. In soil treated with 5 mg/kg Cd, addition of 0.2 g/kg S 0 decreased the diffusive gradients in thin films (DGT) extractable Cd by 60.0%. The application of S 0 significantly decreased the concentration of Cd in rice grain by 12.1% (0.1 g/kg) and 36.6% (0.2 g/kg) respectively. The addition of S 0 significantly increased the ratio of Acidobacteria, Bacteroidetes in rice rhizosphere soil. Meanwhile, the ratio of Planctomycetes and Chloroflexi decreased. The results indicated that promoting Fe- and S-reducing and residue decomposition bacterial in the rhizosphere by S 0 may be one biological reason for reducing Cd risk in the soil-rice system.

Cadmium is a toxic environmental pollutant that is readily absorbed by rice grains and poses serious threats to human health. The selection and breeding of rice varieties with low cadmium accumulation is one of the most economical and ecological methods to reduce cadmium exposure. In this study, two different indica rice grains under cadmium stress were subjected to mass spectrometry-based metabolomics analysis for the first time. When the cadmium concentration increased in rice grains, most carbohydrates and amino acids were down-regulated, except myoinositol that can prevent cadmium toxicity, which was up-regulated. d-Mannitol and l-cysteine were up-regulated with the increase of cadmium concentration in low-cadmium-accumulating rice. Also, organic acids were activated especially 13-(S)-hydroperoxy-9(Z),11(E),15(Z)-octadecatrienoicacid that is related to the alpha-linolenic acid metabolism and jasmonic acid production. The determination of biomarkers and characterization of metabolic pathways might be helpful for the selection of rice varieties with low cadmium accumulation., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

As an important class of flavonoids, anthocyanin has been used to enhance plant-defensive mechanisms against heavy metal stress. However, there are few available reports regarding surface spraying of anthocyanin for reduction of Cd poisoning in rice and its practical applications in paddy fields. After rice growing, measurements were taken of rice growth, pigments, the antioxidant system, thiol compounds, and distribution of Cd in rice tissues. The results showed that surface spraying anthocyanin could promote rice growth, and relative to the control, total chlorophyll significantly increased by 22.62% after surface spraying of 7.5 g L -1 anthocyanin. Simultaneously, Cd accumulation in rice grains was 0.17 ± 0.02 mg kg -1 , which was significantly decreased by 46.88% relative to the control. In the pot experiment (40-day-old rice), treatment with 7.5 g L -1 anthocyanin resulted in decreases of ·O 2 - , H 2 O 2 , and malondialdehyde contents in rice leaves, while the activities of superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase were increased by 59.10, 23.81, 41.75, and 9.39%, respectively. Meanwhile, contents of glutathione, ascorbic acid, non-protein thiols, and phytochelatins showed respective increases of 7.24, 14.49, 42.81, and 41.13% compared with the control value. Subcellular analysis revealed that surface spraying of anthocyanin increased organelle and soluble fractions of Cd in leaf cells. In conclusion, surface spraying of 7.5 g L -1 anthocyanin was mainly attributed to increased antioxidant activities and subcellular sequestration of Cd in organelles and soluble fractions in rice leaves to reduce Cd accumulation in rice grains in the field.

Background: Seafood present important advantages for human nutrition, but it can also accumulate high levels of toxic and potentially toxic elements. Culinary treatments could influence seafood chemical element content and element bioavailability. In this study, the influence of culinary treatments on the total concentration and on the bioavailability of Cd, Cr, Cu and Pb in shark, shrimp, squid, oyster, and scallop was assessed., Methods: Boiling, frying, and sautéing with or without seasonings (salt, lemon juice and garlic) were evaluated. Total concentration and bioavailability of Cd, Cr, Cu and Pb in seafood after all these culinary treatments were compared with those in uncooked samples. Analytes were determined by triple-quadrupole inductively coupled plasma mass spectrometry (ICP-MS/MS). An alternative to express the results avoiding underestimated or overestimated values was proposed., Results: The analytes concentration in seafood without culinary treatment varied from 0.0030 μg g -1 (shrimp) to 0.338 μg g -1 (oyster) for Cd; 0.010 μg g -1 (squid) to 0.036 μg g -1 (oyster) for Cr; 0.088 μg g -1 (scallop) to 8.63 μg g -1 (oyster) for Cu, and < 0.005 μg g -1 (shrimp, squid and oyster) to 0.020 μg g -1 (shark) for Pb. Only Cd (in scallop) was influenced by culinary treatments (reduction from 37 to 53 % after boiling, frying, and sautéing). Bioavailability percentage varied from 11% (oyster) for Cd; 18% (oyster) to 41% (shark) for Cr; 6% (shark) for Cu, and 8% (oyster) for Pb. Bioavailability percentage was not influenced by culinary treatments., Conclusion: Cadmium concentration was reduced in scallop after some culinary treatments (reduction o 37-53% after boiling, frying, and sautéing), but bioavailability percentage was not influenced. The employed analytical method was adequate for the purpose, presenting import results for food safety assessment about the influence of culinary treatments on metals concentration and bioavailability in seafood., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

The chronic exposure of human populations to toxic metals remains a global public health concern. Although chronic Cd exposure is linked to kidney damage, osteoporosis and cancer, the underlying biomolecular mechanisms remain incompletely understood. Since other diseases could also be causally linked to chronic Cd exposure, a systems toxicology-based approach is needed to gain new insight into the underlying exposure-disease relationship. This approach requires one to integrate the cascade of dynamic bioinorganic chemistry events that unfold in the bloodstream after Cd enters with toxicological events that unfold in target organs over time. To this end, we have conducted a systematic literature search to identify all molecular targets of Cd in plasma and in red blood cells (RBCs). Based on this information it is impossible to describe the metabolism of Cd and the toxicological relevance of it binding to molecular targets in/on RBCs is elusive. Perhaps most importantly, the role that peptides, amino acids and inorganic ions, including HCO 3 - , Cl - and HSeO 3 - play in terms of mediating the translocation of Cd to target organs and its detoxification is poorly understood. Causally linking human exposure to this metal with diseases requires a much better integration of the bioinorganic chemistry of Cd that unfolds in the bloodstream with target organs. This from a public health point of view important goal will require collaborations between scientists from different disciplines to untangle the complex mechanisms which causally link Cd exposure to disease., (Copyright © 2020 Elsevier Inc. All rights reserved.)

It is well-known that Cd concentration in the soil, Cd bioavailability, and Cd bioaccumulation in rice (Oryza sativa L.) grains vary greatly in different soil parent materials. Therefore, the classification of agricultural land environmental quality and agricultural land safe usage based on the Cd content in the soil has a wide deviation. By the application of systematic sampling and analysis of soil and rice samples, and in comparison with the different soil parent materials in Heng County, it was found that soil derived from carbonate rocks has higher total Cd and lower mobile Cd proportion than soil from the non-karst areas. This result indicated that soil carbonates raised soil pH and the adsorption of Fe/Mn oxide/hydroxide on Cd significantly reduced the bioavailability of Cd in karst areas. In contrast, acidic soils with relatively lower CaO, TFe 2 O 3 , Mn and total Cd contents, the grown rice plants accumulated higher Cd in their grains. Further research confirmed significant differences in Cd bioaccumulation abilities in the soil between karst and non-karst areas. On this basis, the bioaccumulation factor prediction models of Cd in rice grains were developed in karst and non-karst areas. According to the total concentration of Cd in topsoil samples obtained from the area survey and the predicted Cd content in rice grains, an agricultural land safe usage scheme was put forward. The results showed that the agricultural land classification method based on Cd concentration in the soil and rice grains was more accurate and scientific than that based on the Cd contents in the soil alone., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

A soil microcosm experiment was carried out to quantify the transfer of cadmium (Cd) and lead (Pb) in a multi-species soil system (MS·3). Red earth from Jiangxi (S1), fluvo-aquic soil from Henan (S2), fluvo-aquic soil from Beijing (S3), and black soil from Heilongjiang (S4) were used for soil column packing with S1, S3, or S4 as the 20-50 cm layer and S2, which was Cd- and Pb-contaminated, as the top 0-20 cm layer. For each soil combination, four treatments were set up: CK (no wheat and no earthworm), W (only wheat), E (only earthworm), and E + W (earthworm and wheat). The results showed that the coexistence of earthworm with wheat reduced Cd and Pb contents in wheat plants and earthworms, and increased plant biomass, but had no significant effect on the survival rate and mean weight change rate of earthworms. Total Cd and Pb decreased remarkably in the 0-20 cm layer while increased in the 20-50 cm layer, and approximately 32.8%-51.1% of Cd and 0.35%-7.0% of Pb migrated down into the 20-50 cm soil layers from the 0-20 cm soil layers. The migration varied between the treatments from S2 to S1, S2, and S3. In S2-S1 and S2-S4 columns, the amount of Cd migration decreased when the earthworms coexisted with wheat, while in S2-S3 column, there was no significant difference on such amount regardless of the coexistence of earthworms with wheat. Taken together, the results indicated that the migration of Cd and Pb was not only associated with wheat and earthworm, but also depended on soil types., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The objective of this study was to explore potential microbial mechanisms associated with how water management may alter soil Cd availability under changing pe + pH environments. Four water regimes, aerobic [70% MWHC] + dissolved oxygen, aerobic, continuous flooding, and continuous flooding + N 2 , were applied to Cd-contaminated soil. The results show that the anoxic treatments were effective in decreasing soil pe + pH and in turn decreased Cd availability and increased soil S and Fe availability relative to those of the aerobic treatments. The decreased pe + pH enriched some anaerobic microorganisms such as those in the families Anaerolineaceae and Geobacteraceae. Conversely, other families, such as Gemmatimonadaceae and Sphingomonadaceae, appeared to be sensitive biomarkers that responded to aerobic treatments. Bacterial community structure and network interactions were altered to strengthen bacterial responses to different pe + pH environments as indicated by phylogenetic molecular ecological network (pMEN) analysis. The majority of predicted functional categories, such as metabolism, cell motility, and membrane transport, were affected by different irrigation regimes as indicated by a functional gene profile analysis. The categories were related to important traits that facilitated acclimation of bacteria to their local environment with altered soil pe + pH. Structural equation models revealed that soil pe + pH contributed significantly to soil enzyme activities and differences in bacterial community and function, and consequently, was responsible for the variation of soil Cd availability and iron or sulfur reduction., (Copyright © 2020 Elsevier Inc. All rights reserved.)

This experiment is to explore whether one hyperaccumulator shows the strongly accumulative capacities for low or insoluble Cd compounds in soil. Soil potting experiment was conducted to analyze the accumulation capacity of Solanum nigrum L. for 10 different Cd compounds under two levels. The results clearly indicated: The Cd concentrations of shoots and roots were very high for different Cd compounds in soils even with low or insoluble Cd compounds compared with easily soluble Cd in the treatments of soil contaminated with Cd at different concentrations. Furthermore, the EFs and TFs were all larger than 1 either. Based on the results, although the bioavailabilities of some Cd compounds in soil were lower, S. nigrum's ability to accumulate them was still very strong. Phytoremediation may be widely used to treat with soil contaminated by different cadmium compounds. In addition, the total Cd content is also very important in evaluating the risk of Cd contamination in soil. Thus, phytoextraction is promising., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Consistent use of large amounts of fertilizers, pesticides, and mulch can cause the accumulation of harmful substances in cotton plants. Among these harmful substances, cadmium (Cd), an undegradable element, stands out as being particularly highly toxic to plants. The objective of this study was to evaluate the ability of biochar (3%) and biofertilizer (1.5%) to decrease Cd uptake, increase cotton dry weight, and modulate the activities of photosynthetic and peroxidase (POD), superoxide dismutase (SOD), catalase enzyme (CAT) in cotton (Gossypium hirsutum L.) grown in Cd-contaminated soil (0, 1, 2, or 4 mg Cd kg -1 soil) in pots. These studies showed that, as expected, exogenous Cd adversely affects cotton chlorophyll and photosynthesis. However, biochar and biofertilizer increased cotton dry weight by an average of 16.82% and 32.62%, respectively. Meanwhile, biochar and biofertilizer decreased the accumulation of Cd in cotton organs, and there was a significant reduction in the amount of Cd in bolls (P < 0.05). Biochar and biofertilizer have a positive impact on cotton chlorophyll content, net photosynthesis, stomatal conductance, transpiration rate, and intercellular CO 2 concentration. Thus, the addition of biochar and biofertilizer promote cotton growth. However, biochar and biofertilizer increased the SOD activity of leaves (47.70% and 77.21%), CAT activity of leaves (35.40% and 72.82%), SOD activity of roots (33.62% and 39.37%), and CAT activity of roots (36.91% and 60.29%), respectively, and the addition of biochar and biofertilizer decreased the content of MDA and electrolyte leakage rate. Redundancy analyses showed that biochar and biofertilizer also improved SOD and POD activities by reducing the heavy metal-induced oxidative stress in cotton and reducing Cd uptake in cotton organs. Therefore, biochar and biofertilizer have a positive effect on the growth of cotton.

The exposition of mate (Ilex Paraguariensis A. St.-Hil.) to As and Cd was investigated in plants derived from young mini-cuttings. Mate plants were cultivated in a closed soilless system, composed of coarse sand as substrate and flood fertirrigation. Plantlets were fertirrigated with nutritive solution and As and Cd solutions were added to the nutritive solution in the final concentration of 8 and 17 mg L -1 (As) and of 17 and 33 mg L -1 (Cd) during 14 days. Results show that stem diameter and Dickson quality index (DQI) variables could not be used as a potential indicator of accumulation of As and Cd. The shoot height, number of leaves and chlorophyll index are variables easy and quick to measure and they can be used as parameters to evaluate the stress caused in mate plants cultivation in a closed soilless system. The highest concentration of As and Cd was in roots of plants. Beyond the roots, As and Cd also can be translocated to the leaves achieving high concentrations. In addition, leaves from the treated mate plants were submitted to a hot infusion extraction in order to simulate the traditional beverage and As and Cd were determined in the infusion. Regarding to the infusion procedure, considerable As and Cd amounts were extracted from the leaves leading to conclude that this way of consumption can be an important source of toxic elements for the human diet., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Excessive cadmium (Cd) in rice grain has become a major global public health problem. Here, the effect of foliar glycerol application on Cd accumulation in brown rice was examined. Various spraying concentrations of glycerol between 0.4mM and 50mM were investigated and the results showed that 0.8 mM was the best application concentration for decreasing Cd content in brown rice. After different application period experiment, filling stage was considered as the optimal spraying time. 0.4mM-5mM glycerol application one time at the filling stage could significantly reduce Cd concentration in brown rice by 28.5%-60.4%. Cd transport factors (the ratio of brown rice and flag leaf/node) were decreased by 48.5% and 27.3%, respectively, with glycerol application. Glycerol application also significantly increased Cd concentration in soluble fraction in flag leaf while reduced inorganic Cd and water-soluble Cd in both flag leaf and stem. Our results showed foliar spraying glycerol inhibited Cd transport to brown rice through Cd compartmentalisation in the vacuole and transformation of cadmium chemical form. This study may provide a new method to effectively alleviate the problem of excessive Cd in rice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Pollution of Cd has seriously threatened environmental safety and human health. The field experiment was conducted to investigate the effects of calcium-magnesium phosphate fertilizer and water management on bioavailability of Cd in soils and its accumulation in rice. The results revealed that continuous flooding has enhanced soil pH from 5.10 to 5.72 and reduced soil redox potential (Eh) from 164 to - 60 mV. Application of calcium-magnesium phosphate fertilizer has significantly raised soil pH from 5.10 to 6.45 (P < 0.05). The treatment of calcium-magnesium phosphate fertilizer and continuous flooding has reduced available content of Cd in soils by 28.57%. The content of Cd in brown rice was significantly diminished by 51.36% (P < 0.05). The continuous flooding has promoted formation of residual Cd in soil with application of calcium-magnesium phosphate fertilizer. The biomass and grain production of rice was not significantly decreased compared with control.

Rice production in floodplain deltas is currently vulnerable to climate change and contamination from anthropogenic activities. The relocation of rice production to upland regions could be an option for increasing the sustainability of rice production. Our study evaluated the spatial patterning of heavy metals, i.e., copper (Cu) and cadmium (Cd), in rice along a topogradient from terrace to lowland areas in the Red River basin. The dataset obtained from the analysis of 61 farm sites throughout the whole basin indicated a large discrepancy in the Cu and Cd contents in rice grains from terrace and lowland paddies. While Cu and Cd were not found in most of the rice grain samples from the terrace paddies, the median Cu and Cd contents of the lowland paddy rice were 1.895 and 0.033 mg kg -1 , respectively. Assessing the relationship of Cu and Cd in the soil-rice system to soil properties revealed possible correlations between soil available silicon (Si) and the Cu and Cd contents in rice grain. The enrichment of Si in rice plants likely reduces the translocation of Cu and Cd from soil to grain. Therefore, management of the Si supply, particularly in lowland paddies, should be highlighted as a way to reduce dietary intake of Cu and Cd.

The aim of this study was to summarise the available information regarding the partition of toxic metal (Cd, Hg, Mn, Pb) levels in the maternal/foetal unit from large epidemiological studies. We performed a systematic search of PubMed/MedLine, EMBASE, and ISI Web of Science for papers on Cd, total Hg, Mn or Pb levels in the maternal/cord blood that were published in English (n > = 200; 2010-2017). Data on year of publication, sample size, location, year of survey, and main results were extracted. We found a total of 35 papers. Most studies included large convenience samples of healthy pregnant women. The maternal/cord blood was properly used as a biomarker of prenatal exposure to toxic metals. The partition of these toxic metal levels in the maternal/foetal unit was metal-specific. Cd median levels (IQR) in cord blood reported worldwide were much lower [∼ 70 % < LOD = ± 0.11 μg/L] than those found in maternal blood [0.23 μg/L (0.15-0.35), ∼ 65 % > LOD]. Considering that Cd was under LOD in 70 % of the cord blood, Cd cord:maternal ratio as well as Cd cord proportion were not provided. Total Hg median levels (IQR) in cord blood [0.75 μg/L (0.40-1.19), ∼30 % < LOD = ±0.35 μg/L] were usually higher than in maternal blood [0.55 μg/L (0.40-0.85), ∼ 10 % < LOD = ±0.15 μg/L]. Hg cord:maternal ratio was 1.34 (1.00-1.91), and infants born would have Hg cord:(cord + maternal) proportion ranged from 0.50 to 0.63. Mn was the only metal that was detected in 100 % in both maternal (LOD : ±0.50 μg/L) and cord (LOD = ±0.2 μg/L) blood. Mn median levels (IQR) in cord blood [32.96 μg/L (26.90-40.10)] were 2 times higher than in maternal blood [14.01 μg/L (11.50-17.58)]. Mn cord:maternal ratio was 2.35 (1.09-3.80), and infants born would have Mn proportion ranged from 0.52 to 0.79. Pb median levels (IQR) in cord blood [5.79 μg/L (4.34-8.38), ∼ 5% < LOD : ±2.07 μg/L] were usually equal to or lower than those reported in maternal blood [8.07 μg/L (5.79-10.76), ∼ 1% < LOD = ±1.03 μg/L]. Pb cord:maternal ratio was 0.71 (0.59-0.96), and infants born would have Pb proportion ranged from 0.37 to 0.49. Globally, the results indicate that total Hg and Mn levels were lower in maternal blood but higher in cord blood. However, much greater variability was seen with Cd and Pb. At delivery, total Hg and Pb levels in maternal blood were strong predictors of cord blood levels. Our findings empty that understanding the partition, levels and correlations of toxic metals in the maternal/cord blood may help to elucidate the adverse effects of these metals on foetuses and neonates., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Cadmium (Cd) is an environmental contaminant that triggers toxic effects in various tissues such as the kidney, liver, and lung. Cd can also cause abnormal iron metabolism, leading to anemia. Iron homeostasis is regulated by intestinal absorption. However, whether Cd affects the iron absorption pathway is unclear. We aimed to elucidate the relationship between the intestinal iron transporter system and Cd-induced iron deficiency anemia. C57BL/6J female and male mice, 129/Sv female mice, and DBA/2 female mice were given a single oral dose of CdCl 2 by gavage. After 3 or 24 h, Cd decreased serum iron concentrations and inhibited the expression of iron transport-related genes in the duodenum. In particular, Cd decreased the levels of divalent metal transporter 1 and ferroportin 1 in the duodenum. In addition, human colon carcinoma Caco-2 cells were treated with CdCl 2 . After 72 h, Cd decreased the expression of iron transport-related factors in Caco-2 cells with a pattern similar to that seen in the murine duodenum. These findings suggest that Cd inhibits iron absorption through direct suppression of iron transport in duodenal enterocytes and contributes to abnormal iron metabolism., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The role of metal speciation on metal bioavailability, bio-reactivity and toxicity at the fish intestine is poorly understood. To investigate these processes, we used an in vitro model of the rainbow trout (Oncorhynchus mykiss) intestine, the RTgutGC cell line. Cells were exposed to two essential metals (copper and zinc) and two non-essential metals (cadmium and silver) in a medium of well-defined composition, which allowed the determination of metal speciation in solution. Concentrations resulting in a 50% cell viability reduction (EC 50 ) were measured using a viability assay based on two endpoints: metabolic activity and membrane integrity. Metal bioavailability and bio-reactivity was studied at non-toxic (300 nM all metals) and toxic (EC 10 ; Ag-0.6, Cu-0.9, Cd-3, and Zn-9 μM) concentrations. Bioavailability (i.e. intracellular metal accumulation) was determined by ICP-MS, while bio-reactivity (i.e. induction of a metal specific transcriptional response) was determined by measuring the mRNA levels of a known biomarker of metal exposure (i.e. metallothionein) and of copper and zinc transporters (i.e. ATP7A and ZnT1). Dominant metal species in the exposure medium were Zn 2+ , CuHPO 4 , CdCl + , and AgCl 2 - respectively for Zn, Cu, Cd, and Ag. The EC 50s showed the metal toxicity hierarchy: Ag > Cu > Cd > Zn. In RTgutGC cells, essential metal homeostasis was tightly regulated while non-essential metals accumulated more readily. Non-essential metals were also more bio-reactive inducing higher MT and ZnT1 mRNA levels. Taken together these findings indicate that metal toxicity in RTgutGC cannot solely be explained by extracellular metal speciation but requires the evaluation of metal bioavailability and bio-reactivity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Cadmium (Cd) is an inauspicious abiotic traction that not only influences crop productivity and its growth parameters, but also has adverse effects on human health if these crops are consumed. Among crops, leafy vegetables which are the good source of mineral and vitamins accumulate more Cd than other vegetables. It is thus important to study photosynthetic variables, amino acid composition, and ultrastructural localization of Cd differences in response to Cd accumulation between two low and high Cd accumulating Brassica rapa ssp. chinensis L. (pak choi) cultivars, differing in Cd accumulation ability. Elevated Cd concentrations significantly lowered plant growth rate, biomass, leaf gas exchange and concentrations of amino acids collated to respective controls of both cultivars. Electron microscopy indicated that the impact of high Cd level on ultrastructure of leaf cells was associated to affecting cell functionalities, i.e. irregular cell wall, withdrawal of cell membrane, and chloroplast structure which has negative impact on photosynthetic activities, thus causing considerable plant growth suppression. Damage in root cells were observed in the form of enlargement of vacuole. The energy dispersive micro X-ray spectroscopy of both cultivars leaves indicated that cellular structure exhibited exudates of Cd-dense material. Ultrastructural damages and phytotoxicity were more pronounced in high accumulator cultivar as compared to the low accumulator cultivar. These findings are useful in determining the mechanisms of differential Cd-tolerance among cultivars with different Cd tolerance abilities at cellular level., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Selenium (Se) is an essential trace element. However, Se in soil is often accompanied by heavy metals, such as cadmium (Cd), because of geological background. The safe utilization of such Se-rich land resources remains a challenge. A typical Se-rich area located in Enshi County, China, was systematically investigated with geochemical and epidemiological methods. The results show that Se in the topsoil is 0.84 ± 1.39 μg/g, whereas that of Cd is 0.93 ± 1.63 μg/g. And the concentration of Se and Cd in corn is 0.22 ± 0.96 μg/g and 0.15 ± 0.32 μg/g, respectively, which is mainly related to the high concentrations in soil. The benchmark dose limit of urinary Cd for β2-microglobulin in subjects (n = 160) was calculated as 3.27 µg/g Cr. In view of crop-human dose effect and combining the relationship among the concentrations of crops and human biomarkers and the concentrations of crops and topsoil, this study established the models of land resource safety zoning. With that, the risk screening value of Cd in the soil could be obtained as 0.98 μg/g in this typical area. The proportions of priority utilization, safe utilization, and strict management of agricultural land area were 58.85%, 22.90%, and 18.25%, respectively, in Enshi, China. These results could provide scientific support for local agricultural development and ecological sustainability.

Tomato is the most widespread vegetable crop in the world. In Italy, tomatoes are mainly cultivated in the South and in the Campania region, precisely in the area called Agro Nocerino-Sarnese. This flatland is affected by an extreme level of environmental degradation, especially related to the Sarno River, where concentrations of Potential Toxic Elements (PTEs) have been found to be higher than the maximum permitted level. The aim of this study was to determine the PTEs uptake by roots and their translocation to the aerial parts of the plants of two cultivars of tomatoes (Pomodoro Giallo and San Marzano Cirio 3). To the purpose, samples of the two cultivars were grown both in pots with experimentally contaminated soil containing: Cr or Cd or Pb at extremely high concentrations and in pots with uncontaminated soils (control). Additionally, the antioxidant properties of the cultivars selected grown on uncontaminated/contaminated soils were assessed. The results showed that Cd was the contaminant that most significantly interfered with the growth of both cultivars of tomato plants, whereas Pb caused lower phenotypical damage. Cd translocation from root to the organs of tomato plants was observed in both cultivars. Specifically, the total amount of Cd found in stems and leaves was higher in the Pomodoro Giallo (254.4 mg/kg dry weight) than in the San Marzano Cirio 3 (165.8 mg/kg dry weight). Cd was the only PTE found in the fruits of both cultivars, with values of 6.1 and 3.9 mg/kg dry weight of Pomodoro Giallo and San Marzano Cirio 3, respectively. The fruits of tomato plants grown in PTEs-contaminated soil showed inhibition or stimulations of the radical scavenging activity compared to the fruits grown in uncontaminated soil. This study highlighted that, despite the relatively high experimental concentrations of PTEs, their translocation to the edible part was comparatively low or absent., Competing Interests: The authors have declared that no competing interests exist.

Trace metals are found naturally in soil. However, the increase in industrial and agricultural polluting activities has increased trace metal contamination and raised high concerns in the public health sector. The study was conducted on Origanum syriacum, one of the most consumed herbs in the Middle East, and was divided into three parts. (1) Pot experiment: to study the effect of Cd, Pb, or Ni levels in soil on their uptake by O. syriacum. (2) Field samples: collected from major agricultural regions in Lebanon to analyze Cd, Pb, and Ni concentrations in soil and leaves. (3) Sale outlets samples: to measure the levels of Cd, Pb, and Ni in O. syriacum tissues in the market. Results showed that there was a positive correlation between levels of Cd, Pb, and Ni in soil and those in O. syriacum tissues. None of the field samples contained Pb or Ni that exceeded the maximum allowable limits (MAL). Three samples collected from heavily poultry-manured soil contained Cd higher than the MAL. Samples collected from sale outlets did not exceed the MAL for Ni but two exceeded the MAL for Cd and one for Pb. Trace metal contamination is not a major concern in O. syriacum produced in Lebanon. Only one mixture sample from a sale outlet was higher in Pb than the MAL and three samples from heavily manured fields exceeded the MAL for Cd.

Trace elements such as selenium (Se) and zinc (Zn) are essential elements in the human body, while cadmium (Cd) has no physiological function. A high proportion of people consume dietary supplements to enhance the performance of the body or alter the nutrient contents within the body. Therefore, this study was conducted to evaluate the interaction effects of several popular dietary supplements on the bioaccessibility of Se, Zn and Cd in rice with the hope of identifying dietary supplements that can increase rice Se and Zn bioaccessibility but decrease rice Cd bioaccessibility. The results from in vitro gastrointestinal simulation tests showed that the bioaccessibility of these elements in rice was in the order of Cd (52.07%) > Zn (36.63%) > Se (10.19%) during the gastric phase and Zn (26.82%) > Cd (18.72%) > Se (14.70%) during the intestinal phase. The bioaccessibility of Se during the intestinal phase was greater than that during the gastric phase, and the bioaccessibility of Zn and Cd were the opposite. The bioaccessibility of Se significantly increased in response to vitamin C (VC), vitamin E (VE), vitamin B6 (VB6) and vitamin B9 (VB9), especially VC, which also increased the bioaccessibility of Zn and decreased that of Cd. Procyanidins (OPC), methionine (Met) and coenzyme Q10 (Q10) significantly reduced the bioaccessibility of Se. These results suggest that the reasonable use of dietary supplements can effectively regulate the in vivo contents of trace elements, which provide valuable information for developing health interventions to address problems for specific people, especially selenium-deficient people.

Cadmium (Cd) contaminated soil has threatened plant growth and human health. Rapeseed (Brassica napus L.), an ideal plant for phytoremediation, is an important source of edible vegetable oil, vegetable, animal fodder, green manure and biodiesel. For safe utilization of Cd polluted soil, physiological, biochemical, and molecular techniques have been used to understand mechanisms of Cd tolerance in B. napus. However, most of these researches have concentrated on vegetative and adult stages, just a few reports focus on the initial growth stage. Here, the partitioning of cadmium, gene expression level and activity of enzymatic antioxidants of H18 (tolerant genotype) and P9 (sensitive genotype) were investigated under 0 and 30 mg/L Cd stress at seedling establishment stage. Results shown that the radicle length of H18 and P9 under Cd stress were decreased by 30.33 (0.01 < P < 0.05) and 88.89% (P < 0.01) respectively. Cd concentration at cotyledon not radicle and hypocotyl in P9 was significantly higher than that in H18. The expression level of BnaHMA4c, which plays a key role in root-to-shoot translocation of Cd, was extremely higher in P9 than in H18 under both normal and Cd stress conditions. We also found that SOD, CAT and POD were more active in responding to Cd stress after 48 h, and the activity of SOD and CAT in H18 were higher than that in P9 at all observed time points. In conclusion, high activity of enzymatic antioxidants at initial Cd stress stage is the main detoxification mechanism in Cd-tolerant rapeseed, while the higher Cd transfer coefficient, driven by higher expression level of BnaHMA4c is the main mechanism for surviving radicle from initial Cd toxicity in Cd-sensitive rapeseed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Hydroponic experiment was conducted to investigate the biochemical responses and accumulation behaviour of cadmium (Cd) in aquatic fern, Ceratopteris pteridoides, under four different levels of exposure. Plants were grown in 10 μM (CdT1), 20 μM (CdT2), 40 μM (CdT3) and 60 μM (CdT4) concentrations of Cd for 12 consecutive days and Cd accumulation in different plant parts, cell levels and growth medium was estimated. In C. pteridoides, Cd removal kinetics was best described by pseudo-second-order kinetic model. Increased accumulation of Cd in the plants was detected in a concentration dependent manner with maximum under 60 μM of Cd (CdT4) exposure (191.38 mg kg -1 , 186.19 mg kg -1 and 1316.34 mg kg -1 in leaves, stems and roots, respectively). Cell wall of C. pteridoides is identified as crucial Cd storage site with the highest (28-69%) accumulation followed by organelles (14-44%) and soluble fraction (6-46%). Increased leaf proline, malondialdehyde (MDA) and protein content with significant reduction (P < 0.05) in chlorophyll concentration and upregulation of antioxidant enzymes catalase (CAT), guaiacol peroxidase (POD) and superoxide dismutase (SOD) reveals the presence of Cd resistance mechanism in C. pteridoides. Calculated higher (>1) bioconcentration factor (BCF) and lower (<1) translocation factor (TF) values evinced the suitability of C. pteridoides in Cd phytostabilization rather than phytoextraction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Cadmium (Cd) contamination in agricultural soil is a worldwide environmental problem. In situ stabilization has been considered an effective approach for the remediation of Cd-contaminated agricultural soil. However, information about the long-term effects of amendment on soil properties and stabilization efficiency remains limited. In the present study, mercapto-functionalized nano-silica (MPTS/nano-silica) was used to stabilize Cd in contaminated agricultural soil under field conditions for three years (with application rates of 0%, 0.2%, 0.4%, 0.6%, 0.8% and 1.0%). The application of MPTS/nano-silica reduced the soil aggregate stability (PDA 0.25 ) (14.8%) and available K (24.9%) and significantly increased the soil dehydrogenase (DHA) (43.4%), yield of wheat grains (33.5%) and Si content in wheat tissues (55.2% in leaf, 50.4% in stem, and 37.7% in husk) (p < 0.05). More importantly, MPTS/nano-silica decreased the leachability (36.0%) and bioavailability (54.3%) of Cd in the soil and transformed Cd into a more stable fraction. The content of Cd in wheat grains decreased by 53.9%, 61.9% and 54.1% in 2017, 2018 and 2019, respectively, in comparison with the control. These results indicated that MPTS/nano-silica has long-term stabilization effects on Cd in agricultural soil and is a potential amendment for the remediation of Cd-contaminated agricultural soils., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Contamination of arable land with trace metals is a global environmental issue which has serious consequences on human health and food security. Present study evaluates the adsorption of cadmium (Cd) and lead (Pb) by using different quantities of composite of sepiolite, organic manure and lime (SOL) at field and laboratory scale (batch experiments). Characterization of SOL by SEM, EDS and FTIR spectroscopy revealed the presence of elemental and functional groups (hydroxyl, C⋯H and -COOH groups) on its surface. The field experiment was performed in a paddy field of gleysol having moderate contamination of Cd and Pb (0.64 mg kg -1 and 53.44 mg kg -1 ). Here, different rates of SOL (0.25, 0.5, 1, 1.5 and 2% w/w) were applied by growing low and high Cd accumulator rice cultivars. Application of SOL at 2% w/w showed considerable efficiency to increase soil pH (up to 19%) and to reduce available Cd (42-66%) and Pb (22-55%) as compared to the control. Moreover, its application reduced metal contents in roots, shoots and grains of rice by 31%, 36% and 72% (for Cd) and 41%, 81% and 84% (for Pb), respectively in low accumulator cultivar. Further, the batch sorption experiment was performed to evaluate the adsorption capacity of SOL in a wide range of contamination. Obtained sorption data was better fitted to the Langmuir equation. Our results highlight the strong efficiency of composite treatment for an enhanced in-situ metal immobilization under field and lab conditions. Further, applied treatments greatly reduced the metal contents in rice grains. In a nut shell, application of SOL in a contaminated gleysol should be considered for soil remediation and safe food production., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The relationship between the chemical forms of Cu 2+ and Cd 2+ adsorbed on the roots of different wheat cultivars and their phytotoxic effects on the plants were investigated. The wheat varieties Dunmaiwang (DMW), Tekang 6 (TK6), Zhongmai895 (ZM895), and Chaojixiaomai (AK68) were used. The zeta potentials of wheat roots, measured by the streaming potential method, were used to characterize root charge properties. Results indicated that the changes in zeta potential at pH 4.01-6.61 were 14.7, 15.53, 13.01, and 12.06 mV for ZM895, AK68, DMW, and TK6, respectively. The negative charge and functional groups on ZM895 and AK68 roots were greater than on DMW and TK6 roots, which led to more exchangeable and complexed Cu 2+ and Cd 2+ on ZM895 and AK68 roots and increased Cu 2+ and Cd 2+ toxicity compared to DMW and TK6. Coexisting cations, such as Ca 2+ , Mg 2+ , K + , and NH 4 + , alleviated Cu 2+ and Cd 2+ toxicity to wheat roots through competition for adsorption sites on the roots, which decreased exchangeable and complexed Cu 2+ and Cd 2+ on wheat roots. The Ca 2+ and Mg 2+ were most effective in alleviating heavy metal toxicity and they decreased exchangeable Cu 2+ on AK68 roots by 39.14% and 47.82%, and exchangeable Cd 2+ by 8.51% and 28.23%, respectively., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Whether cadmium ingestion affects the susceptibility to infection and the detailed mechanism have not been investigated. We aimed to evaluate the effects of cadmium on the intestinal mucosal barrier and Salmonella infection. We found that oral administration of cadmium caused damage to the intestinal mucosal barrier, with body weight loss, an increase in inflammation, significantly reduced Muc2 expression and goblet cell loss in the intestine. The effect of cadmium on secretory cell differentiation was further demonstrated to be regulated by the overactivation of the Notch signaling pathway by increased production of ROS both in mice and in intestinal organoids. The damage of cadmium to the intestinal barrier, and goblet cell and Paneth cells loss, dramatically increased susceptibility to enteropathogensinfection at a low dose (10 2 CFU), with a high death ratio, body weight loss and severe intestinal inflammation. However, enteropathogens susceptibility and intestinal barrier damage enhanced by cadmium was alleviated by inhibiting ROS production and Notch pathway activation, with reversion of goblet cell loss. This study indicated cadmium didn't only affect the integrity of intestinal barrier and epithelial differentiation, but also increased the risk of enteropathogenic infection from food contamination or environmental pollution, which signals an alarm for public health., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Soil co-contaminated with cadmium (Cd) and decabromodiphenyl ether (BDE-209) is a widespread environmental problem, especially in electronic waste contaminated surroundings. Accumulation of Cd and BDE-209 in crops has possibly harmful effects on local human health. In order to assess the potential of arbuscular mycorrhizal (AM) fungi and amaranth (Amaranthus hypochondriacus L.) in remediation of soil co-contaminated with Cd and BDE-209, pot trials were performed to investigate interactive effects of AM fungi, Cd and BDE-209 on growth of amaranth, uptake of Cd and BDE-209, distribution of chemical forms of Cd and activities of antioxidant enzymes in shoots and dissipation of BDE-209 in soil. The present results showed that shoot biomass of non-mycorrhizal plants was significantly inhibited by increasing of Cd addition (5-15 mg kg -1 ), but were only slightly declined with BDE-209 addition (5 mg kg -1 ). The interaction of Cd and BDE-209 reduced the proportions of ethanol- and d-H 2 O-extractable Cd in shoots, consequently alleviated Cd toxicity to plants and enhanced root uptake of Cd and BDE-209. Inoculation of AM fungi resulted in significantly greater shoot biomass as well as higher concentrations of Cd and BDE-209 compared with non-mycorrhizal treatment. Moreover, AM fungi played a beneficial role in relieving oxidative stress on amaranth by increasing the activities of dismutase (SOD) and catalase (CAT) in shoots and significantly improved the dissipation of BDE-209 in soil. The present study suggested that combination of AM fungi and amaranth may be a potential option for remediation of Cd and BDE-209 co-contaminated soils., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Agricultural production of Ligusticum chuanxiong Hort. is often affected by heavy metal pollution in soil, especially mixtures of cadmium (Cd) and lead (Pb). We assessed metal-induced phytotoxicity in L. chuanxiong by exposing the plants to soil treated with Cd, Pb, or Cd/Pb mixtures. A combined Cd/Pb treatment alleviated the inhibition in plant growth, photosynthesis, and secondary metabolite generation seen in single-metal exposures in three of the four combinations. Most combined Cd/Pb treatments resulted in preferential uptake of magnesium, copper, and nitrogen in underground plant parts and accumulation of phosphorus and calcium in aboveground plant parts, thereby leading to improvements in photosynthetic potential. Compared with single-metal exposures, combined Cd/Pb treatment significantly decreased the contents of Cd by 16.67%-40.12% and Pb by 10.68%-21.70% in the plant, respectively. At the subcellular level, the Pb presence increased the Cd percentage associated with cell wall from 64.79% to 67.93% in rhizomes and from 32.76% to 45.32% in leaves, while Cd reduced Pb contents by 9.36%-46.39% in the subcellular fractions. A combined Cd/Pb treatment decreased the contents of water- and ethanol-extractable metal forms and increased the contents of acetic acid- and hydrochloric acid-extractable forms. The lower toxic effects of the Cd/Pb mixture in L. chuanxiong were associated with photosynthetic potential, subcellular distribution, the chemical forms of Cd and Pb, and synthesis of secondary metabolites. These findings are useful for plant production strategies in soils contaminated by heavy metals., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Trace metal elements are significant stressors in urban areas. Their harmful effects on physiological parameters are demonstrated, but current laboratory studies are not representative of wild chronic exposure to a trace metal cocktail. Calcium can reduce the accumulation and toxicity of several metals, but soil acidification in cities leads to a decrease in bioavailability of this element. The objective of this study was to investigate the accumulation and toxicity of a trace metal cocktail representative of urban exposure on passerine birds, and test the importance of calcium availability on these toxic effects. We exposed zebra finches (Taeniopygia guttata) to a cocktail of seven metals and one metalloid in drinking water, with or without calcium supplementation. We monitored the concentration of metals in the blood and feathers, and their effects on oxidative status and telomere length. The metal cocktail led to higher concentration of all elements in the feathers, and of arsenic and lead in the blood. Birds with a higher concentration of cadmium, arsenic and lead in the feathers had shorter telomeres, but no impact of the cocktail was detected on oxidative status. Birds of the 'calcium' group and the 'calcium and metal' group accumulated higher concentrations of zinc, chromium and nickel in feathers. The 'calcium and metal' group also accumulated lower concentrations of arsenic and lead in feathers compared to the 'metal' group. Our results suggest that chronic exposure to a cocktail of metals at low concentrations has deleterious effects on birds, which can be limited through calcium intake., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Cadmium (Cd) exposure has been implicated in the perturbation of energy metabolism and the development of cardiometabolic disease, but disease predisposition from chronic low-dose Cd exposure remains unclear. This study employed a mouse model to investigate the toxic effects of chronic Cd exposure at food limitation-relevant levels on energy metabolism and the associated liver and gut microbiome functions. Results showed that the Cd exposure induced the perturbation of energy metabolism in mice, evidenced by the alteration of various metabolites associated with the phosphorogen (adenosine triphosphate-creatine phosphate) system, tricarboxylic acid cycle, and lipid metabolism, as well as the increase of the cardiometabolic risk factor, triglyceride. Moreover, both liver and gut microbiome underwent marked structural/histological and functional alterations, prone to the onset of cardiometabolic disease following the Cd exposure. Certain hepatic transcription factors and gut microbes, specifically PPARα, SREBP1c, HNF4A and the Clostridiales&#95;vadinBB60&#95;group, were identified to be highly correlated with altered urinary metabolites, revealing potential toxicological interactions between the liver and gut microbiome, and energy metabolism. Our findings provide new insights into the progression of metabolic diseases induced by Cd exposure. We also propose a stricter Cd limitation in future food safety standards., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The biochemical responses of Bellamya aeruginosa as a dominant and widespread freshwater gastropod throughout China to waterborne cadmium (Cd) were investigated to explore the impacts of exposure concentration and duration in this potential sentinel species. After the 7 days' test of dosage-mortality relationship, gastropods were exposed for either 7 days at the LC 50 (1.7 mg/L), the LC 10 (0.7 mg/L) and 0.02 mg/L Cd, or 28 days at 0.02 mg/L Cd. A suite of biochemical indicators including metallothionein-like protein (MTLP), reduced glutathione (GSH), catalase (CAT), contents of tissue metal (Cd, Fe, Mn, Cu, Zn), and the compartments of these metals bound to MTLP were examined. The treatment of 0.02 mg/L Cd led to the increase of Cd bound to MTLP (Cd-MTLP) levels, the decrease of GSH content, and the upregulation of CAT activity, but no induction of MTLP, indicating that the intrinsic MTLP and GSH worked together for the detoxification of Cd at the low exposure. When the exposure concentration increased, GSH was depleted severely and synthesis of MTLP was triggered, leading to a strong and significant relationship between MTLP level and Cd accumulation. At the lethal concentrations (1.7 mg/L), both MTLP induction and CAT activity were inhibited while the proportion of Cd-MTLP to total Cd were increased, suggesting more intrinsic MTLP were utilized to sequester free Cd ions. Therefore, the content of Cd-MTLP in digestive glands of B. aeruginosa was recommended as a reliable biomarker for Cd contamination., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: This study aims to observe the effect on urine and sweat excretion levels of cadmium (Cd) and lead (Pb) in healthy men in a maximum incremental test until exhaustion and repeated exposure to heat., Methods: twenty-nine adult men divided into control group (CG; n = 14) and experimental group (EG; n = 15) performing two maximum tests until exhaustion in normothermia (22 °C) and hyperthermia (42 °C). EG experienced 9 sessions of heat exposure at high temperatures (100 °C) (HEHT). After the nine sessions, the initial tests were repeated in both groups. Urine samples were collected before and after each test. After the hyperthermia tests, sweat samples were gathered., Results: Urinary Cd increased after initial tests in GC and in hyperthermia in EG (p < 0.05). Urinary excretion of Pb rose after HEHT (p < 0.05). Pb in sweat was higher in EG than in CG after HEHT (p < 0.05)., Conclusion: Heat exercise and constant exposure to heat can be a valid method to increase the excretion of toxic metals., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The uptake and accumulation of cadmium (Cd) in Salvia miltiorrhiza (Bge.) negatively affects the quality of its harvested roots, and seriously threatens human health. This study investigates the effect of a microbial inoculant (MI) and garbage enzyme (GE) on Cd uptake, the accumulation of bioactive compounds, and the community composition of microbes in the rhizosphere soil of S. miltiorrhiza under Cd stress. S. miltiorrhiza seedlings were transplanted to Cd-contaminated pots and irrigated with an MI, GE, a combination of an MI and GE (MIGE) or water (control). The results indicated that treatments with an MI, GE or MIGE can reduce Cd uptake in S. miltiorrhiza. The MIGE treatment had greater efficiency in reducing Cd uptake than the control (reduction by 37.90%), followed by the GE (25.31%) and MI (5.84%) treatments. Treatments with an MI, GE and MIGE had no significant impact on fresh and dry root biomass. Relative to the control, the MI treatment had the highest efficiency in increasing the accumulation of total tanshinones (an increase of 40.45%), followed by the GE treatment (40.08%), with the MIGE treatment (9.90%) treatment not having a more favorable effect than the separate application of an MI or GE. The salvianolic acid content for all groups was higher than the standard prescribed by Chinese pharmacopoeia, notwithstanding a slightly lower level in the treated groups relative to the control. In addition, metagenomic analysis indicated changes in the relative abundance of soil microbes associated with the bioremediation of heavy metals. The relative abundances of Brevundimonas, Microbacterium, Cupriavidus and Aspergillus were significantly greater in the treated groups than in the Control. These results suggest that using MI and GE, either separately or together, may not only improve the quality of S. miltiorrhiza but may also facilitate the microbial remediation of soil contaminated with Cd., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Radiolabeled tracers allow visualization of not only perfusion, but receptors, function, and metabolism as well. Although spatial resolution is lower than that of computed tomography and magnetic resonance imaging, positron emission tomography (PET) and single photon emission computed tomography (SPECT) have great potential for target-specific imaging. In this review, we discuss several SPECT and PET tracers used in brain imaging, specifically focusing on tracers currently available, or developed, in Japan. Several important and sophisticated methods exist for analysis of brain PET and SPECT images. Two of them, quantitative cerebral blood flow measurement and voxel-based statistical analysis are discussed in this review. The former method, which employs acetazolamide loading, is useful for evaluation of the brain perfusion reserve for ischemic brain diseases. The latter is useful in diagnosing dementing diseases. Additionally, great strides have been made in the development of the technology used in the scanners. New SPECT systems based on cadmium-zinc-telluride, PET/MRI, and semiconductor PET/CT may provide higher spatial resolution with an acquisition time shorter than ever before. Such developments of both tracers and scanners can be integrated for unprecedented imagery of the brain, providing valuable insight into underlying causes of some fatal brain disorders.

The black soldier fly larvae (BSFL) have become a promising candidate for waste disposal and are an ideal feed source for animal nutrition. The uptake of heavy metals could influence the growth of BSFL, but the effects of heavy metal pressures on the gut microbiota of BSFL are largely uncharacterized. Here, we examine the influences of Cu and Cd on the growth and gut microbiota of BSFL as well as the distribution of accumulated heavy metals in the larvae and their feces. Exposure to Cu (from 100 to 800 mg/kg) and Cd (from 10 to 80 mg/kg) did not significantly inhibit the weight gain of BSFL. With elevated exposure doses, the contents of both Cu and Cd accumulated in the bodies and feces of BSFL were remarkably increased. In the BSFL feces, Cu mainly existed as residues, while Cd mainly existed as either water-soluble states (in the low-exposure groups) or residues (in the high-exposure groups). Cd was more readily enriched (47.1%-91.3%) than Cu (<30%) in vivo. More importantly, exposure to Cu and Cd remarkably altered the gut microbiota of BSFL, particularly in the phyla Proteobacteria, Firmicutes and Bacteroidetes. High exposure to the metals (i.e., Cu-800 and Cd-80 groups) substantially decreased the abundances of most of the dominant families, but significantly stimulated the enrichment of Brucellaceae, Enterobacteriaceae, Alcaligenaceae, Campylobacteraceae, and Enterococcaceae. Moreover, the bacterial diversity in the BSFL gut was significantly reduced following high exposure to the metals. These results may fill a gap in our knowledge of the effects of heavy metals on the intestinal microbiome of BSFL., (Copyright © 2020 Elsevier Inc. All rights reserved.)