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Hexavalent chromium [Cr(VI)] is an established human lung carcinogen, but the carcinogenesis mechanism is poorly understood. Chromosome instability, a hallmark of lung cancer, is considered a major driver of Cr(VI)-induced lung cancer. Unrepaired DNA double-strand breaks are the underlying cause, and homologous recombination repair is the primary mechanism preventing Cr(VI)-induced DNA breaks from causing chromosome instability. Cell culture studies show acute Cr(VI) exposure causes DNA double-strand breaks and increases homologous recombination repair activity. However, the ability of Cr(VI)-induced DNA breaks and repair impact has only been reported in cell culture studies. Therefore, we investigated whether acute Cr(VI) exposure could induce breaks and homologous recombination repair in rat lungs. Male and female Wistar rats were acutely exposed to either zinc chromate particles in a saline solution or saline alone by oropharyngeal aspiration. This exposure route resulted in increased Cr levels in each lobe of the lung. We found Cr(VI) induced DNA double-strand breaks in a concentration-dependent manner, with females being more susceptible than males, and induced homologous recombination repair at similar levels in both sexes. Thus, these data show this driving mechanism discovered in cell culture indeed translates to lung tissue in vivo., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Honey bees are important plant pollinators and honey producers. Contamination of the environment with metals can lead to a decline in honey bee populations. Copper (Cu) and zinc (Zn) salts are commonly used as fungicides and foliar fertilizers. In this study, we investigated the effects of 10-day chronic oral exposure to different concentrations of Cu (CuSO4) and Zn (ZnCl2) on survival and feeding rates of Carniolan honey bees in laboratory conditions. We found that mortality in honey bee workers increased in a concentration-dependent manner and that Cu (lethal concentration [LC50] = 66 mg/l) was more toxic than Zn (LC50 = 144 mg/l). There was no difference in the feeding rate of Cu-treated bees for the different concentrations tested, but the feeding rate decreased with the increase in Zn concentration. To determine feeding preference or avoidance for Cu and Zn, we conducted 2-choice 24-h feeding experiments. We demonstrated that honey bees preferred Zn-containing solutions compared to the control diet. A two-choice experiment with Cu showed a tendency for honey bees to be deterred by Cu at high concentrations; however, it was not statistically significant. In summary, our results suggest that honey bee workers may suffer adverse effects when exposed to ecologically relevant concentrations of Cu and Zn., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America.)

Despite the promising applications of the use of quantum dots (QDs) in the biomedical field, the long-lasting effects of QDs on the cell remain poorly understood. To comprehend the mechanisms underlying the toxic effects of QDs in yeast, we characterized defects associated with receptor-mediated endocytosis (RME) as well as pinocytosis using Saccharomyces cerevisiae as a model in the presence of cadmium selenide/zinc sulfide (CdSe/ZnS) QDs. Our findings revealed that QDs led to an inefficient RME at the early, intermediate, and late stages of endocytic patch maturation at the endocytic site, with the prolonged lifespan of GFP fused yeast fimbrin (Sac6-GFP), a late marker of endocytosis. The transit of FM1-43, a lipophilic dye from the plasma membrane to the vacuole, was severely retarded in the presence of QDs. Finally, QDs caused an accumulation of monomeric red fluorescent protein fused carbamoyl phosphate synthetase 1 (mRFP-Cps1), a vacuolar lumen marker in the vacuole. In summary, the present study provides novel insights into the possible impact of CdSe/ZnS QDs on the endocytic machinery, enabling a deeper comprehension of QD toxicity.

Hexavalent chromium [Cr(VI)] is considered a major environmental health concern and lung carcinogen. However, the exact mechanism by which Cr(VI) causes lung cancer in humans remains unclear. Since several reports have demonstrated a role for inflammation in Cr(VI) toxicity, the present study aimed to apply transcriptomics to examine the global mRNA expression in human lung fibroblasts after acute (24 h) or prolonged (72 and 120 h) exposure to 0.1, 0.2 and 0.3 μg/cm 2 zinc chromate, with a particular emphasis on inflammatory pathways. The results showed Cr(VI) affected the expression of multiple genes and these effects varied according to Cr(VI) concentration and exposure time. Bioinformatic analysis of RNA-Seq data based on the Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and MetaCore databases revealed multiple inflammatory pathways were affected by Cr(VI) treatment. qRT-PCR data corroborated RNA-Seq findings. This study showed for the first time that Cr(VI) regulates key inflammatory pathways in human lung fibroblasts, providing novel insights into the mechanisms by which Cr(VI) causes lung cancer., 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 Inc. All rights reserved.)

Quantum dots (QDs) receive widespread attention in industrial and biomedical fields, but the risks posed by the use of nanoparticles to aquatic organisms and the associated toxicological effects are still not well understood. In this study, effects of the 7-day dietary exposure of Salmo trutta fario L. juveniles to CdSe/ZnS-COOH QDs were evaluated at molecular, cellular, physiological and whole-organism levels. Fish feeding with QDs-contaminated feed resulted in an increased somatic index of the liver, a genotoxic effect on peripheral blood erythrocytes, altered enzyme activity and decreased MDA level. Furthermore, Cd levels in the gills and liver tissues of the exposed fish were found to be significantly higher than in those of the control fish. Alpha diversity indexes of the gut microbiota of the QDs-exposed S. trutta fario L. individuals exhibited a decreasing trend. The principal coordinate analysis (PCoA) showed that the gut microbiota of the control fish was significantly different from that of the fish exposed to QDs (p < 0.05). Additionally, the linear discriminant analysis (LDA) performed using an effect size (LEfSe) algorithm unveiled 19 significant taxonomic differences at different taxonomic levels between the control group and the QDs-exposed group. In the QDs-exposed group, the relative abundance of the genus Citrobacter (Proteobacteria phylum) in the gut microbiota was found to be significantly increased whereas that of the genus Mycoplasma (Tenericutes phylum) significantly decreased compared to the control group. In summary, QDs-contaminated diet affects the gut microbiota of fish by significantly changing the relative abundance of some taxa, potentially leading to dysbiosis. This, together with morphophysiological, cytogenetic and biochemical changes, poses a risk to fish 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 © 2023 Elsevier B.V. All rights reserved.)

Quantum dots (QDs) have been highly sought after in the past few decades for their potential to be used in many biomedical applications. However, QDs' cytotoxicity is still a major concern that limits the incorporation of QDs into cutting-edge technologies. Thus, it is important to study and understand the mechanism by which QDs exert their toxicity. Although many studies have explored the cytotoxicity of quantum dots through the transcriptomic level and reactive species generation, the impact of quantum dots on the expression of cellular protein remains unclear. Using Saccharomyces cerevisiae as a model organism, we studied the effect of cadmium selenide zinc sulfide quantum dots (CdSe/ZnS QDs) on the proteomic profile of budding yeast cells. We found a total of 280 differentially expressed proteins after 6 h of CdSe/ZnS QDs treatment. Among these, 187 proteins were upregulated, and 93 proteins were downregulated. The majority of upregulated proteins were found to be associated with transcription/RNA processing, intracellular trafficking, and ribosome biogenesis. On the other hand, many of the downregulated proteins are associated with cellular metabolic pathways and mitochondrial components. Through this study, the cytotoxicity of CdSe/ZnS QDs on the proteomic level was revealed, providing a more well-rounded knowledge of QDs' toxicity.

Quantum dots (QDs) inhibit fish hatching, but the mechanism is still unclear. In this study, the effect of Indium phosphide/zinc sulfide quantum dots (InP/ZnS QDs) on the embryo incubation of rare minnow was investigated. Five experimental concentration groups were set up according to the preliminary experimental results, which were 0, 50, 100, 200 and 400 nM. A direct exposure method was adopted to expose embryos to InP/ZnS QDs solution. The results showed that InP/ZnS QDs significantly inhibited the embryo hatching rate, delayed embryo emergence, affected the expression of genes associated with hatching gland cells and hatching enzymes. InP/ZnS QDs also destroy the structure of the embryo chorion. In addition, QDs can cause oxidative stress in embryos. Transcriptional sequencing analysis showed that InP/ZnS QDs InP/ZnS QDs may have induced the production of a hypoxic environment and triggered induce abnormal cardiac muscle contraction, inflammatory response and apoptosis process in embryos. In conclusion, QDs influences embryo hatchability largely through egg chorion mediation., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest. They 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 © 2023. Published by Elsevier B.V.)

Irregular plagues of house mice, Mus musculus, incur major economic impacts on agricultural production in Australia. The efficacy of zinc phosphide (ZnP), the only registered broadacre control agent for mice, is reported as increasingly variable. Have mice become less sensitive over time or are they taking a sub-lethal dose and developing aversion? In this laboratory study, the sensitivity of mice (wild caught; outbred laboratory strain) was assessed using oral gavage of a range of ZnP concentrations. The estimated LD 50 values (72-79 mg ZnP/kg body weight) were similar for each mouse group but are significantly higher than previously reported. The willingness of mice to consume ZnP-coated grains was determined. ZnP-coated grains (50 g ZnP/kg grain) presented in the absence of alternative food were consumed and 94% of wild mice died. Mice provided with alternative food and ZnP-coated wheat grains (either 25 or 50 g ZnP/kg grain) consumed toxic and non-toxic grains, and mortality was lower (33-55%). If a sublethal amount of ZnP-coated grain was consumed, aversion occurred, mostly when alternative food was present. The sensitivity of wild house mice to ZnP in Australia is significantly lower than previously assumed. Under laboratory conditions, ZnP-coated grains coated with a new higher dose (50 g ZnP/kg grain) were readily consumed. Consumption of toxic grain occurred when alternative food was available but was decreased. Our unambiguous findings for house mice indicate a re-assessment of the ZnP loading for baits used for control of many rodents around the world may be warranted., (© 2022 CSIRO Health and Biosecurity. Integrative Zoology published by International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)

CuInS 2 /ZnS-PEG quantum dots (QDs) are among the most widely used near infrared non-cadmium QDs and are favored because of their non-cadmium content and strong tissue penetration. However, with their increasing use, there is great concern about whether exposure to QDs is potentially risky to the environment and humans. Furthermore, toxicological data related to CuInS 2 /ZnS-PEG QDs are scarce. In the study, we found that CuInS 2 /ZnS-PEG QDs (0-100 μg/mL) could internalize into human LAD2 mast cells without affecting their survival rate, nor did it cause degranulation or release of IL-8 and TNF-α. However, CuInS 2 /ZnS-PEG QDs significantly inhibited Substance P (SP) and LL-37-induced degranulation and chemotaxis of LAD2 cells by inhibiting calcium mobilization. Lower concentrations of CuInS 2 /ZnS-PEG QDs promoted the release of TNF-α and IL-8 stimulated by SP, but higher concentrations of CuInS 2 /ZnS-PEG QDs significantly inhibited the release of TNF-α and IL-8. On the other hand, CuInS 2 /ZnS-PEG QDs promoted LL-37-mediated TNF-α release from LAD2 cells in a dose-dependent manner from 6.25 to 100 μg/mL, while release of IL-8 triggered by LL-37 was dose-dependently inhibited within a dose concentration of 12.5-100 μg/mL. Collectively, our data demonstrated that CuInS 2 /ZnS-PEG QDs differentially mediated human mast cell activation induced by SP and LL-37., 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 © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Commercially used quantum dots (QDs) exemplify complex nanomaterials with multiple components, though little is known about the type of interactions between these components in determining the overall toxicity of this material. We synthesized and characterized a functional QD (CdSe/ZnS&#95;P&E) that was identical in structure and composition to a patented and commercially applied QD and the combinations of its components (CdSe, CdSe/ZnS, ZnS, CdSe&#95;P&E, ZnS&#95;P&E, and P&E). Cells exposed to incremental concentrations of these materials were investigated for cell viability and cellular perturbations, contributing to a final common pathway of cell death using high-content screening assays in model human intestinal epithelial cells (HIEC-6). The concentrations that resulted in a loss of 20% cell viability (EC 20 values) for each tested component were used for estimating the combination index (CI) to evaluate synergistic or antagonistic effects between the components. Complete QD (core/shell-polymer) showed the highest toxic potential due to synergistic interactions between core and surface functional groups. The cationic polymer coating enhanced cellular uptake of the QD, ensuing lysosome acidification and release of heavy metal ions to the intracellular milieu, and caused oxidative stress and cytotoxicity. Overall, this study advances our understanding of the collective contribution of individual components of a functional QD toward its toxic potential and emphasizes the need to study multilayered nanomaterials in their entirety for hazard characterization.

Cartilage development is a sensitive process that is easily disturbed by environmental toxins. In this study, the toxicity of CdSe/ZnS quantum dots on the skeleton of the next generation (F1) was evaluated using rare minnows (Gobiocypris rarus) as model animals. Four-month-old sexually mature parental rare minnows (F0) were selected and treated with 0, 100, 200, 400 and 800 nmol/L CdSe/ZnS quantum dots for 4 days. Embryos of F1 generation rare minnows were obtained by artificial insemination. The results showed that with increasing maternal quantum dots exposure, the body length of F1 embryos decreased, the overall calcium content decreased, and the deformity and mortality rates increased. Alcian blue staining results showed that the lengths of the craniofacial mandible, mandibular arch length, mandibular width, and CH-CH and CH-PQ angles of larvae of rare minnows increased; histological hematoxylin-eosin staining further indicated that quantum dots affected the development of chondrocytes. Furthermore, high concentrations of CdSe/ZnS quantum dots inhibited the transcript expression of the bmp2b, bmp4, bmp6, runx2b, sox9a, lox1 and col2α1 genes. In conclusion, CdSe/ZnS quantum dots can affect the skeletal development of F1 generation embryos of rare minnows at both the individual and molecular levels, the damage to the craniofacial bone is more obvious, and the toxic effect of high concentrations of quantum dots (400 nmol/L and 800 nmol/L) is more significant., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Hexavalent chromium [Cr(VI)] is a global environmental pollutant and human lung carcinogen. However, the mechanisms of Cr(VI) carcinogenesis are not well defined. Cr(VI)-altered gene expression has been reported in the literature and is implicated in numerous mechanisms of Cr(VI) carcinogenesis. MicroRNAs (miRNAs) play a key role in controlling gene expression and are associated with carcinogenic mechanisms. To date no studies have evaluated global changes in miRNA expression in human cells after Cr(VI) exposure. We used RNA sequencing to evaluate how a particulate Cr(VI) compound (zinc chromate), the most potent form of Cr(VI), alters global miRNA expression after acute (24 h) or prolonged (72 and 120 h) exposure to 0.1, 0.2 and 0.3 μg/cm 2 zinc chromate in an immortalized, non-cancerous human lung cell line (WTHBF-6). Particulate Cr(VI) significantly affected expression of miRNAs at all time points and concentrations tested. We also found the number of significantly downregulated miRNAs increased in a time- and concentration-dependent manner and many miRNAs were upregulated after 24 h exposure at the intermediate concentration tested. Pathway analyses of the differentially expressed miRNAs predicted miRNAs target pathways of Cr(VI) carcinogenesis in a time- and concentration-dependent manner. These data are the first to evaluate global changes in miRNA expression in human lung cells after Cr(VI) exposure and indicate miRNAs may play a key role in pathways of Cr(VI) carcinogenesis., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The investigation of the combined toxic action of different types of nanoparticles (NPs) and their interaction between each other and with aquatic organisms is an important problem of modern ecotoxicology. In this study, we assessed the individual and mixture toxicities of cadmium and zinc sulfides (CdS and ZnS), titanium dioxide (TiO 2 ), and two types of mesoporous silicon dioxide (with no inclusions (SMB3) and with metal inclusions (SMB24)) by a microalga growth inhibition bioassay. The counting and size measurement of microalga cells and NPs were performed by flow cytometry. The biochemical endpoints were measured by a UV-VIS microplate spectrophotometer. The highest toxicity was observed for SMB24 (EC50, 3.6 mg/L) and CdS (EC50, 21.3 mg/L). A combined toxicity bioassay demonstrated that TiO 2 and the SMB3 NPs had a synergistic toxic effect in combinations with all the tested samples except SMB24, probably caused by a "Trojan horse effect". Sample SMB24 had antagonistic toxic action with CdS and ZnS, which was probably caused by metal ion scavenging.

The development of QDs-based fluorescent bionanoprobe for cellular imaging fundamentally relies upon the precise knowledge of particle-cell interaction, optical properties of QDs inside and outside of the cell, movement of a particle in and out of the cell, and the fate of particle. We reported engineering and physicochemical characterization of water-dispersible Eu 3+ /Mn 2+ co-doped ZnSe@ZnS core/shell QDs and studied their potential as a bionanoprobe for biomedical applications, evaluating their biocompatibility, fluorescence behaviour by CytoViva dual mode fluorescence imaging, time-dependent uptake, endocytosis and exocytosis in RAW 264.7 macrophages. The oxidation state and local atomic structure of the Eu dopant studied by X-ray absorption fine structure (XAFS) analysis manifested that the Eu 3+ ions occupied sites in both ZnSe and ZnS lattices for the core/shell QDs. A novel approach was developed to relieve the excitation constraint of wide bandgap ZnSe by co-incorporation of Eu 3+ /Mn 2+ codopants, enabling the QDs to be excited at a wide UV-visible range. The QDs displayed tunable emission colors by a gradual increase in Eu 3+ concentration at a fixed amount of Mn 2+ , systematically enhancing the Mn 2+ emission intensity via energy transfer from the Eu 3+ to Mn 2+ ion. The ZnSe:Eu 3+ /Mn 2+ @ZnS QDs presented high cell viability above 85% and induced no cell activation. The detailed analyses of QDs-treated cells by dual mode fluorescence CytoViva microscopy confirmed the systematic color-tunable fluorescence and its intensity enhances as a function of incubation time. The QDs were internalized by the cells predominantly via macropinocytosis and other lipid raft-mediated endocytic pathways, retaining an efficient amount for 24 h. The unique color tunability and consistent high intensity emission make these QDs useful for developing a multiplex fluorescent bionanoprobe, activatable in wide-visible region.

ZnSe/ZnS quantum dots (QDs) have excellent optical properties, but researchers have not clearly determined whether they cause harm to organisms. In the present study, the effect of ZnSe/ZnS QDs on the parents and offspring of rare minnow were evaluated for the first time. Exposure to ZnSe/ZnS QDs altered the testicular structure, caused sperm DNA damage and decreased sperm motility in males. They also suppressed the expression of reproduction-related genes, such as androgen receptor (Ar), DM-related transcription factor 1 (Dmrt1), estrogen receptor (Er), and X-ray repair cross complementing gene 1 (Xrcc1). Continued monitoring of the F1 generation revealed that the embryonic development of the F1 generation was abnormal and the growth index of the F1 generation of adult fish showed hormesis. A comet assay showed that the F1 generation still had DNA damage in the 400 and 800 nmol/L groups at 96 h post-fertilization (hpf). Thus, ZnSe/ZnS QDs damaged the reproductive system of the rare minnow, and this effect continued to the F1 generation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The primary focus of our research was to obtain global gene expression data in baker's yeast exposed to sub-lethal doses of quantum dots (QDs), such as green-emitting CdSe/ZnS and InP/ZnS, to reveal novel insights on their unique mechanisms of toxicity. Despite their promising applications, their toxicity and long-lasting effects on the environment are not well understood. To assess toxicity, we conducted cell viability assays, ROS detection assays, and assessed their effects on the trafficking of Vps10-GFP toward the trans -Golgi network with confocal microscopy. Most notably, we used RNA-sequencing (RNA-seq) to obtain gene expression profiles and gene identities of differentially expressed genes (DEGs) in QD-treated yeast. We found CdSe/ZnS QDs significantly altered genes implicated in carboxylic acid, amino acid, nitrogen compounds, protein metabolic processes, transmembrane transport, cellular homeostasis, cell wall organization, translation, and ribosomal biogenesis. Additionally, we found InP/ZnS QDs to alter genes associated with oxidation-reduction, transmembrane transport, metal ion homeostasis, cellular component organization, translation, and protein and nitrogen compound metabolic processes. Interestingly, we observed an increase in reactive oxygen species (ROS) in CdSe/ZnS-treated cells and a decrease in ROS levels in InP/ZnS-treated cells. Nevertheless, we concluded that both QDs modestly contributed cytotoxic effects on the budding yeast.

Increased applications of quantum dots (QDs) in the biomedical field have aroused attention for their potential toxicological effects. Although numerous studies have been carried out on the toxicity of QDs, their effects on reproductive and development are still unclear. In this study, we systematically evaluated the male reproductive toxicity and developmental toxicity of CdSe/ZnS QDs in BALB/c mice. The male mice were injected intravenously with CdSe/ZnS QDs at the dosage of 2.5 mg/kg BW or 25 mg/kg BW, respectively, and the survival status, biodistribution of QDs in testes, serum sex hormone levels, histopathology, sperm motility and acrosome integrity was measured on Day 1, 7, 14, 28 and 42 after injection. On Day 35 after treatment, male mice were housed with non-exposed female mice, and then offspring number, body weight, organ index and histopathology of major organs, blood routine and biochemical tests of offspring were measured to evaluate the fertility and offspring health. The results showed that CdSe/ZnS QDs could rapidly distribute in the testis, and the fluorescence of QDs could still be detected on Day 42 post-injection. QDs had no adverse effect on the structure of testis and epididymis, but high-dose QDs could induce apoptosis of Leydig cells in testis at an early stage. No significant differences in survival of state, body weight organ index of testis and epididymis, sex hormones levels, sperm quality, sperm acrosome integrity and fertility of male mice were observed in QDs exposed groups. However, the development of offspring was obviously influenced, which was mainly manifested in the slow growth of offspring, changes in organ index of main organs, and the abnormality of liver and kidney function parameters. Our findings revealed that CdSe/ZnS QDs were able to cross the blood-testis barrier (BTB), produce no discernible toxic effects on the male reproductive system, but could affect the healthy growth of future generations to some extent. In view of the broad application prospect of QDs in biomedical fields, our findings might provide insight into the biological safety evaluation of the reproductive health of QDs., (Copyright © 2021. Published by Elsevier Inc.)

The extensive use of semiconducting nanoparticles such as quantum dots in biomedical and industrial products can lead to their inadvertent release into the freshwater system. Natural exudates in the aquatic system comprising extracellular polymeric substance (EPS) and protein-rich metabolites can eventually adsorb onto the quantum dots (QDs) surface and form an eco-corona. The alterations in the physio-chemical and toxicological behavior of CdSe/ZnS QDs under the influence of eco-corona in the freshwater system have not been explored yet. In the present study, lake water medium conditioned with exudate secreted by Scenedesmus obliquus was utilized as an eco-corona forming matrix. The time-based evolution of the eco-corona on the differently charged CdSe/ZnS QDs was analyzed using transmission electron microscopy and dynamic light scattering. Aging of amine-QDs in algal exudate for 72 h showed enhanced aggregation (Mean Hydrodynamic Diameter- 1969 nm) as compared to carboxyl-QDs (1543 nm). Further, eco-coronation tends to impart an overall negative charge to the QDs. The fluorescence intensity of amine-QDs was quenched by 84% due to the accumulation of higher eco-corona. An integrative effect of surface charge and accumulated eco-corona layer influenced the Cd 2+ ion leaching from the QDs. An enhancement in the algal cell viability treated with carboxyl - CdSe/ZnS (90%) and amine- CdSe/ZnS QDs (94%) aged for 72 h suggested that eco-corona can effectively mitigate the inherent toxicity of the QDs. The oxidative stress markers in the algal cells (LPO, SOD, and CAT) were in correlation with the cytotoxicity results. The algal photosynthetic efficiency depended on the deposition of eco-coronated QDs on the cell surface. Cellular uptake results indicated low Cd 2+ concentration of nearly 13.9 and 11.5% for carboxyl- and amine- CdSe/ZnS QDs respectively. This suggests that eco-coronation directly influences the bioavailability of engineered nanoparticles., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Quantum dots (QDs) are new types of nanomaterials. Few studies have focused on the effect of different surface modified QDs on embryonic development. Herein, we compared the in vivo toxicity of CdSe/ZnS QDs with carboxyl (-COOH) and amino (-NH 2 ) modification using zebrafish embryos. After exposure, the two CdSe/ZnS QDs decreased the survival rate, hatching rate, and embryo movement of zebrafish. Moreover, we found QDs attached to the embryo membrane before hatching and the eyes, yolk and heart after hatching. The attached amount of carboxyl QDs was more. Consistently, the Cd content in embryos and larvae was higher in carboxyl QD-treatment. We further observed that the two QDs caused zebrafish pericardial edema and cardiac dysfunction. In line with it, both carboxyl and amino QDs up-regulated the transcription levels of cardiac development-related genes, and the levels were higher in carboxyl QD-treated groups. Furthermore, the chelator of Cd 2+ diethylene triamine pentacetate acid could partially rescued the developmental toxicity caused by the two types of QDs suggesting that both the nature of QDs and the release of Cd 2+ contribute to the developmental toxicity. In conclusion, the two CdSe/ZnS QDs have developmental toxicity and affect the cardiac development, and the carboxyl QDs is more toxic possibly due to the higher affinity and more release to embryos and larvae. Our study provides new knowledge that the surface functional modification of QDs is critical on the development on aquatic species, which is beneficial to develop and applicate QDs more safely and environment-friendly., (Copyright © 2020. Published by Elsevier B.V.)

The assessment of cytotoxicity of quantum dots is very essential for environmental and health risk analysis. In the present work we have modelled HeLa cell cytotoxicity of sixty one CdSe quantum dots with ZnS shell as a function of its experimental conditions and molecular construction using quasiSMILES representations. The index of ideality of correlation helps in the building of ten statistically significant models having good fitting ability with value of R 2 ranging from 0.8414 to 0.9609 for the training set. The split 5 model is rated as the best model with values of R 2 , Q 2 F1 , Q 2 F2 and Q 2 F3 as 0.8964, 0.8267, 0.8264 and 0.8777 respectively for the calibration set. The extraction of features causing increase and decrease of cytotoxicity of quantum dots indicates importance of neutral surface charge, surface modified with protein, 72 h exposure time, combination of MTT assay with surface protein in decreasing the cytotoxicity. Amphiphilic polymer, polyol ligand with neutral charge, 0.5 - 0.6 nm quantum dot diameter with lipid ligand and unmodified positively charged surface are grouped in toxicity enhancer features. Further, consensus modelling using split 5 and 8 patterns enhances the prediction quality by increasing the R 2 val to 0.9361 and 0.9656 respectively., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Hepatocellular carcinoma (HCC) is highly resistant to anticancer therapy and novel therapeutic strategies are needed. Chronotherapy may become a promising approach because it may improve the efficacy of antimitotic radiation and chemotherapy by considering timing of treatment. To date little is known about time-of-day dependent changes of proliferation and DNA damage in HCC. Using transgenic c-myc/transforming growth factor (TGFα) mice as HCC animal model, we immunohistochemically demonstrated Ki67 as marker for proliferation and γ-H2AX as marker for DNA damage in HCC and surrounding healthy liver (HL). Core clock genes (Per1, Per2, Cry1, Cry2, Bmal 1, Rev-erbα and Clock) were examined by qPCR. Data were obtained from samples collected ex vivo at four different time points and from organotypic slice cultures (OSC). Significant differences were found between HCC and HL. In HCC, the number of Ki67 immunoreactive cells showed two peaks (ex vivo: ZT06 middle of day and ZT18 middle of night; OSC: CT04 and CT16). In ex vivo samples, the number of γ-H2AX positive cells in HCC peaked at ZT18 (middle of the night), while in OSC their number remained high during subjective day and night. In both HCC and HL, clock gene expression showed a time-of-day dependent expression ex vivo but no changes in OSC. The expression of Per2 and Cry1 was significantly lower in HCC than in HL. Our data support the concept of chronotherapy of HCC. OSC may become useful to test novel cancer therapies., (© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.)

The use of different types of quantum dots is growing in recent times in both the technology and biomedical industries. Such is the extension of the use of these quantum dots that they have become potential emerging contaminants, which makes it necessary to evaluate their potential toxicity and the impact they may have on both health and the environment. Although studies already exist in this regard, the molecular mechanisms by which CdSe/ZnS quantum dots exert their toxic effects are still unknown. For this reason, in this study, a comprehensive proteomic approach has been designed, applying the SILAC strategy to an in-vitro model (hepatic cells) and the super-SILAC alternative to an in-vivo model, specifically zebrafish larvae. This integral approach, together with additional bioanalytical assays, has made it possible for the identification of proteins, molecular mechanisms and, therefore, biological processes that are altered as a consequence of exposure to CdSe/ZnS quantum dots. It has been demonstrated, on the one hand, that these quantum dots induce hypoxia and ROS generation in hepatic cells, which leads to apoptosis, specifically through the TDP-43 pathway. On the other hand, it has been shown that exposure to CdSe/ZnS quantum dots has a high impact on developing organisms, inducing serious neural and developmental problems in the locomotor system., 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.)

Background: Hexavalent chromium [Cr(VI)] is a human lung carcinogen and global marine pollutant. High Cr concentrations, resembling the ones observed in occupationally exposed workers, have been observed in fin whales (Balaenoptera physalus) in the Gulf of Maine. This outcome suggests Cr might be disrupting the health of fin whale populations. Indeed, Cr in acute (24 h) exposure does cause toxicity in fin whale cells. However, human cell culture data indicate prolonged exposures (120 h) induce a higher amount of toxicity compared to 24 h exposure due to an inhibition of homologous recombination repair. However, whether prolonged exposure causes similar outcomes in fin whale cells is unknown., Objective: Due to the importance of assessing prolonged exposure toxicity, this study focuses on characterizing acute and prolonged exposure of Cr(VI) in male and female fin whale cells., Methods: Cytotoxicity was measured by the clonogenic assay, also known as colony forming assay, which measures the ability of cells to proliferate and form colonies after the treatment. DNA double strand breaks were analyzed by neutral comet assay. Clastogenicity was measured using the chromosome aberration assay. Intracellular Cr levels were measured with Graphite Furnace Atomic Absorption Spectrometry (GFAAS) with Syngistix Software., Results: In this study, we demonstrate that particulate Cr(VI) induces cytotoxicity and genotoxicity in a treatment-dependent manner after 24 h and 120 h exposures. Cytotoxicity levels were generally low with relative survival above 64 %. DNA double strand break data and chromosome aberration data were elevated after a 24 h exposure, but decreased after a 120 h exposure. While cytotoxicity was similar after 24 h and 120 h exposures, less DNA double strand breaks and chromosomal instability occurred with prolonged exposure., Conclusion: Particulate Cr(VI) is cytotoxic and genotoxic to fin whale cells after acute and prolonged exposures. The reduction of genotoxicity we have observed after 120 h exposure may be partly explained by lower intracellular Cr levels after 120 h. However, the decrease in intracellular levels is not reflected by a similar decrease in chromosome aberrations suggesting other mechanisms may be at play. Male fin whale cells appear to be more susceptible to the genotoxic effects of particulate Cr(VI) while female cells are less susceptible possibly due to increased cell death of damaged cells, but more work is needed to clarify if this outcome reflects a sex difference or interindividual variability. Overall, the study shows particulate Cr(VI) does induce toxicity at both acute and prolonged exposures in fin whales cells indicating Cr(VI) exposure is a health risk for this species., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Objective: This study aimed to the evaluate the nephrotoxicity of CdSe/ZnS QDs in vitro and vivo , as well as investigate the underlying toxicity mechanisms., Results: In vitro experiments showed that compared with control cells, CdSe/ZnS QDs treatment significantly inhibited cell viability and promoted cell apoptosis in dose-dependent manner in NRK cells. Notably, CdSe/ZnS QDs treatment increased the contents of MDA and ROS, and decreased the activities of SOD, CAT and GSH-Px; however, the co-treatment of NAC and QDs relieved the oxidative damage of NRK cells. Moreover, in vivo experiments also revealed that CdSe/ZnS QDs treatment obviously increased kidney weight coefficient, damaged the kidney function, as well as induced inflammatory response and inhibited the activation of NRF2/Keap1 pathway in kidney tissues of mice., Conclusions: CdSe/ZnS QDs exhibited obvious nephrotoxicity by mediating oxidative damage and inflammatory response in vitro and in vivo via NRF2/Keap1 pathway., Methods: The characterization of CdSe/ZnS QDs was analyzed by transmission electron microscope, emission spectrum scanning, and dynamic light scattering. Rat kidney cells (NRK) were exposed to different doses of CdSe/ZnS QDs with or without N-acetylcysteine (NAC, antioxidant). Then, cellular uptake of CdSe/ZnS QDs was detected, and in vitro cytotoxicity was evaluated by MTT assay and TUNEL assay.

Recent researches have demonstrated that many nanoparticles are harmful to spermatogenesis. However, the reported nanoparticles -elicited testicular pathologies have been mostly confined to hormone levels and sperm quality and quantity, the detail mechanism is still largely unknown and the strategies to reduce the toxicity of nanoparticles on testis are lacking. Here, we found that CdSe/ZnS quantum dots (QDs) exposure impair double-strand break (DSB) repair in spermatocyte, leading to the disruption of meiotic progression and thus cell apoptosis and decreased sperm production. Furthermore, we found that QDs exposure elevates the autophagy. Crucially, both in vitro and in vivo studies indicated that elevated autophagy could down-regulate the expression of the genes responsible for homologous recombination, which is the main pathway for DSB repair during meiosis, indicating that spermatogenesis impairment by CdSe/ZnS QDs is mediated by autophagy. Consequently, injection of autophagy inhibitor (3-MA) restore DSB repair in spermatocytes, resulting in prevention of spermatocyte apoptosis and recovery of spermatogenesis. Our studies strongly indicate that autophagy is key for eliciting the spermatogenesis dysfunction after nanoparticle exposure, and autophagy inhibition can be used as a potential clinical remedy for alleviating the male reproductive toxicity of nanoparticles., Competing Interests: Declaration of Competing Interest There are no conflicts to declare., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Despite the versatility of quantum dots (QDs) in optoelectronics and biomedical field, their toxicity risks remain a considerable hindrance for clinical applications. Cytotoxicity of Cadmium containing QDs is well documented and reveals that they are toxic to cells. Reports suggest that the presence of toxic elements at the QD core (e.g., cadmium, selenium) is responsible for its toxicity in in vivo and in vitro levels. Hence, here the toxicity of heavy metal free ZnSe/ZnS QDs on two scenarios were assessed, (i) HEK cells as in vitro system and (ii) Swiss Albino mice as in vivo model. Before toxicity analysis, QDs subjected to various optical and physico-chemical characterization methods such as absorption and emission spectra analysis, observation under U.V light, TEM, DLS, Zeta potential, FTIR, Raman and XPS spectra, ICP-OES, TGA and DTG curve. It is very necessary to characterize the synthesized QDs because their toxicity greatly influenced by the physico-chemical properties. On checking the vulnerability of HEK cells on exposure to ZnSe/ZnS QDs, the obtained results disclose that ZnSe/ZnS QDs showed merest impact on cellular viability at a concentration less than 100 μg/ml. Acute toxicity of 10 mg/kg ZnSe/ZnS QDs was studied in mice and no clinical or behavioural changes were observed. It did not induce any changes in haematological parameters and any loss of body or organ weight. Moderate pathological changes were evident only in the liver, all others organs like kidney, spleen and brain did not show any manifestations of toxicity. Current work lays substantial bedrock for safe biomedical and environmental application of ZnSe/ZnS QDs in near future., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Quantum dots (QDs) comprise an emerging group of materials with innumerable number of possibilities in biological research including cellular labelling. Among the leading members in this category, ZnSe/ZnS quantum dots (QDs) hold greater attractive possibilities in imaging primarily due to their higher biocompatibility and dispersibility. Nevertheless, the inherent toxicity of ZnSe/ZnS QDs is not yet completely explored which largely compromise most of their biomedical application potential. Strong blue emitting water soluble QDs effectively synthesized by aqueous phase route. Synthesized QDs further subjected to various optical and physicochemical characterization. Approximately 5-6 nm sized ZnSe/ZnS QDs illuminated bluish green fluorescence under UV lamp. Present study addresses possible adverse effects of ZnSe/ZnS QDs in hepatic system using HepG2 cells; which is the routinely employed in vitroliver cell model. A bundle of assays wasperformed out to reveal the cytotoxic nature of ZnSe/ZnS QDs and the mechanism behind it. Herein, absorption, distribution, metabolism, excretion and toxicity (ADME and T) of ZnSe/ZnS in mice were profiled in detail followed by intravenous (i.v.) and intraperitoneal (i.p.) administration at a dose of 10 mg/kg body weight. In a short review, it could be state that ZnSe/ZnS QDs did not exhibit any significant in vivo toxicity outcome in mice., (Copyright © 2020 Elsevier B.V. All rights reserved.)

InP QDs have shown a great potential as cadmium-free QDs alternatives in biomedical applications. It is essential to understand the biological fate and toxicity of InP QDs. In this study, we investigated the in vivo renal toxicity of InP/ZnS QDs terminated with different functional groups-hydroxyl (hQDs), amino (aQDs) and carboxyl (cQDs). After a single intravenous injection into BALB/c mice, blood biochemistry, QDs distribution, histopathology, inflammatory response, oxidative stress and apoptosis genes were evaluated at different predetermined times. The results showed fluorescent signals from QDs could be detected in kidneys during the observation period. No obvious changes were observed in histopathological detection or biochemistry parameters. Inflammatory response and oxidative stress were found in the renal tissues of mice exposed to the three kinds of QDs. A significant increase of KIM-1 expression was observed in hQDs and aQDs groups, suggesting hQDs and aQDs could cause renal involvement. Apoptosis-related genes (Bax, Caspase 3, 7 and 9) were up-regulated in hQDs and aQDs groups. The above results suggested InP/ZnS QDs with different surface chemical properties would cause different biological behaviors and molecular actions in vivo. The surface chemical properties of QDs should be fully considered in the design of InP/ZnS QDs for biomedical applications.

Several studies have reported the presence of smithsonite (ZnCO 3 ) in soils polluted by zinc mining. The present study aimed to determine upper critical threshold values of Zn phytotoxicity in a substrate spiked with ZnCO 3 and to compare them with those obtained in field-collected soils. We studied Zn toxicity to perennial ryegrass (Lolium perenne L.) grown in pots with unpolluted peat treated with increasing concentrations of ZnCO 3 that produced nominal total Zn concentrations of 0, 0.7, 1.3, 2.0, 2.6, and 3.3%. To keep constant near-neutral pH value in all the treatments, we used decreasing concentrations of dolomitic lime. In the treatment with total soil Zn of 3.3% (pH 6.8), the foliar Zn concentration of L. perenne was 1914 ± 211 mg kg -1 , falling into the range of 2400 ± 300 mg kg -1 reported for Lolium species grown under similar laboratory conditions in a polluted soil (total soil Zn 5.4%, pH 7.3) collected near a Zn smelter. The value of 92 ± 98 mg kg -1 was obtained for the median effective concentration (EC50) values of 0.01 M KNO 3 -extractable Zn using the responses of shoot dry biomass, shoot length, and total pigments. This value falls within the range of 95 ± 46 mg kg -1 reported in other studies for the EC50 values of salt-extractable Zn using field-collected soils. The application of ZnCO 3 for spiking was able to mimic foliar Zn concentrations of Lolium species observed in field-collected soils. The effective concentrations of soil Zn obtained in the present study are comparable to those obtained in field-collected soils. Future research should determine effective concentrations of metals using soils spiked with metal-containing compounds that mimic a real source of contamination. Environ Toxicol Chem 2020;39:1790-1796. © 2020 SETAC., (© 2020 SETAC.)

The increasing heavy metal contamination in agricultural soils has become a serious concern across the globe. The present study envisages developing microbial inoculant approach for agriculture in Zn contaminated soils. Potential zinc tolerant bacteria (ZTB) were isolated from zinc (Zn) contaminated soils of southern Rajasthan, India. Isolates were further screened based on their efficiency towards Zn tolerance and plant growth promoting activities. Four strains viz. ZTB15, ZTB24, ZTB28 and ZTB29 exhibited high degree of tolerance to Zn up to 62.5 mM. The Zn accumulation by these bacterial strains was also evidenced by AAS and SEM-EDS studies. Assessment of various plant growth promotion traits viz., IAA, GA 3 , NH 3 , HCN, siderophores, ACC deaminase, phytase production and P, K, Si solubilization studies revealed that these ZTB strains may serve as an efficient plant growth promoter under in vitro conditions. Gluconic acid secreted by ZTB strains owing to mineral solubilization was therefore confirmed using high performance liquid chromatography. A pot experiment under Zn stress conditions was performed using maize (Zea mays) variety (FEM-2) as a test crop. Zn toxicity reduced various plant growth parameters; however, inoculation of ZTB strains alleviated the Zn toxicity and enhanced the plant growth parameters. The effects of Zn stress on antioxidant enzyme activities in maize under in vitro conditions were also investigated. An increase in superoxide dismutase, peroxidase, phenylalanine ammonia lyase, catalase and polyphenol oxidase activity was observed on inoculation of ZTB strains. Further, ZIP gene expression studies revealed high expression in the ZIP metal transporter genes which were declined in the ZTB treated maize plantlets. The findings from the present study revealed that ZTB could play an important role in bioremediation in Zn contaminated soils.

This study provides a preliminary characterization of a metallothionein (MT) gene in Septifer virgatus and highlights its potential use in biomonitoring. The full-length SvMT cDNA and the complete sequence of the SvMT gene were identified using reverse transcriptase PCR coupled with the rapid amplification of cDNA ends and the primer walking method. The SvMT cDNA encodes a protein of 72 amino acids having nine classical Cys-X-Cys motifs. Moreover, the deduced amino acids contained the conserved motif (Cys-x-Cys-x(3)-Cys-Thr-Gly-x(3)-Cys-x-Cys-x(3)-Cys-x-Cys-Lys) of MT family 2. Its molecular mass and isoelectric point were estimated to be 7.01 kDa and 7.00, respectively. BLAST-based searching indicated that SvMT shared 81.0% amino acid sequence identity with Mytilus edulis MT-20-II. The SvMT gene has three coding exons and two introns. After exposure to 1 mg/L cadmium chloride, the expression of SvMT increased 15-fold by 3 days (d), with a maximum expression of 27-fold by 5 d compared with the pre-exposure level. After exposure to 2 mg/L zinc chloride, the expression of SvMT increased 2.5-fold by 3 d and 4.7-fold by 5 d compared with the pre-exposure level. A significant increase in the expression level of SvMT mRNA was observed after the exposure of S. virgatus to the combination of 0.003 mg/L cadmium chloride and 0.2 mg/L zinc chloride compared with the pre-exposure level. Our work indicates that the SvMT gene is associated with stress responses and could be a potential biomarker for marine pollution.

Autophagy molecules such as microtubule-associated protein light chain 3 (LC3) and p62/SQSTM1 have been used as biomarkers of protective or conversely adverse effects of exposure to toxicants. In the present study we show changes in LC3-II (a lipidated form of LC3-I) and p62 levels in response to zinc compounds and some other toxicants in J774.1 murine macrophages. The cytotoxicity of either ZnO or ZnSO 4 largely depended on the concentration of FBS or albumin in the culture medium. Accordingly, these authophagy markers were more remarkably increased when the cells were exposed to ZnO or ZnSO 4 in the absence of FBS. We next addressed lysosomal function impairment and changes in LC3-II and p62 levels following exposure to TiO 2 , ZnO, and ZnSO 4 . Lysosomal pH was quickly decreased by autolysosome inhibitors such as bafilomycin A1 and chloroquine, while TiO 2 , ZnO and ZnSO 4 did not decrease lysosomal pH. However, the amounts of LC3-II and p62 and the LC3-II/LC3-I ratio were increased either by the lysosomal inhibitors and the Zn compounds. LC3-II and p62 levels were increased after exposure to arsenite and lipopolysaccharide (LPS). The p62 and phospho-p62 levels were also increased by either ZnSO 4 and bafilomycin A1 in HEK293 cells stably expressing RFP-LC3. The current observations suggest that LC3-II and p62 levels were increased as consequences of early effects of toxicants without changing lysosomal pH., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

CdTe quantum dots (QDs) are still widely considered as excellent fluorescent probes because of their far more superior optical performance and fluorescence efficiency than non‑cadmium QDs. Thus, it is important to find ways to control their toxicity. In this study, CdTe QDs and CdTe@ZnS QDs both could cause IL-1ß-mediated inflammation following with pyroptosis in BV2 cells, but the toxic effects caused by CdTe@ZnS QDs was weaker than CdTe QDs, which demonstrated the partial protection of ZnS shell. When investigating the molecular mechanisms of QDs causing the inflammatory injury, the findings suggested that cadmium-containing QDs exposure activated NF-κB that participated in the NLRP3 inflammasome priming and pro-IL-1ß expression. After that, QDs-induced excessive ROS generation triggered the NLRP3 inflammasome activation and resulted in active caspase-1 to process pro-IL-1ß into mature IL-1ß release and inflammatory cell death, i.e. pyroptosis. Fortunately, the inhibitions of caspase-1, NF-κB and ROS or knocking down of NLRP3 all effectively attenuated the increases in the IL-1ß secretion and cell death caused by QDs in BV2 cells. This study provided two methods to alleviate the toxicity of cadmium-containing QDs, in which one is to encapsulate bare-core QDs with a shell and the other is to inhibit their toxic pathways. Since the latter way is more effective than the former one, it is significant to evaluate QDs through a mechanism-based risk assessment to identify controllable toxic targets., Competing Interests: Declaration of Competing Interest Authors of this article declare that there are no conflicts of competing financial interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

We studied changes in the transcription of genes encoding cytokines (TNF, IL-6, IL-10, and IL-32), cell activation markers (ICAM1, CD38, Fas, and FCGRIII), ROS production catalyst (NOX2), autophagy (Beclin 1, LC3B, and p62) and apoptosis (BAX, BCL2) regulators in peripheral blood mononuclear cells upon contact with quantum dots CdSe/ZnS-MPA and CdSe/CdSeZnS/ZnS-PTVP. Up-regulation of TNF, ICAM1, Fas, p62 mRNA and down-regulation of the FCGRIII and NOX2 mRNA in response to the presence of quantum dots were revealed. The formation of serum protein corona on the surface of quantum dots abolished this effect.

For the first time, we report the design and fabrication of a ZnS nanoparticle-decorated silica fibre mesh (ZnS@SiO 2 ) for localized H 2 S-amplified chemotherapy. With incorporation of DOX, implanted ZnS@SiO 2 fibres enable sufficient on-site drug dosage and intracellular H 2 S content, inducing significant in vitro and in vivo tumour inhibition.

The annual increase in the production and the use of engineering quantum dots (QDs) have led to concern about exposure and safety of QDs. To resolve the risk of Cd release from QDs, a series of Cd-free QDs, represented by CuInS 2 /ZnS QDs, has been developed in recent years. However, the toxicological profile of CuInS 2 /ZnS QDs has not been fully elucidated, especially, their immunotoxicity. Here, we performed a detailed in vitro cytotoxicity study on PEGylated CuInS 2 /ZnS QDs using the DC2.4 cell line and investigated their in vivo immunotoxicity using BALB/c mice. In vitro experiments showed that CuInS 2 /ZnS QDs were taken up by cells, promoted cell viability, enhanced release of tumor necrosis factor-α, and decreased the level of interleukin (IL)-6 in response to lipopolysaccharide stimulation. More than 5000 genes at the transcriptome level were observed by high-throughput RNA sequencing after CuInS 2 /ZnS QD exposure. In vivo study showed that CuInS 2 /ZnS QDs increased the levels of IL-4 on day 1 and enhanced the levels of IL-10 and IL-13 on day 28 in mice. There was no obvious difference in the number of spleen-derived lymphocytes, organic index, hematology and immune organ histology on days 1 and 28 after treatment. These findings demonstrated that PEGylated CuInS 2 /ZnS QDs disturbed the function of DC2.4 immune cells in vitro , but caused no obvious toxicity to immune system in vivo , suggesting that PEGylated CuInS 2 /ZnS QDs are biocompatible and have potential for bioapplication in the future.

Present study was conducted to report the effect of variable doses of neodymium zirconate zinc sulfide nanocomposite on behavior of albino mice of both sexes. Five-week-old albino mice (C57BL/6 strain) of both sexes were orally treated either with 10 mg (low dose) or 20 mg/ml saline/kg body weight (high dose) of neodymium zirconate zinc sulfide nanocomposite for 11 days. An untreated control group was maintained in parallel for same duration that received saline solution orally. A series of neurological (rotarod, light and dark box, open field, and novel object recognition) tests were conducted in all treatments. Oral supplementation of both low and high dose of nanocomposite significantly reduced the rotarod test performance as well as stretch attend reflex in male mice during light dark box test. Male mice treated with high dose of neodymium zirconate zinc sulfide nanocomposite had significantly increased time mobile and decreased time immobile than control group during open field test. Female mice treated with 10 mg/ml saline/kg body weight of neodymium zirconate zinc sulfide nanocomposite had significantly more line crossing during trial 1, and they spend more time with object A during trial 2 of novel object recognition test than their saline-treated control group. Change in body weight remained unaffected when compared between nanocomposite treated and untreated albino mice. In conclusion, we are reporting that both the applied doses of neodymium zirconate zinc sulfide nanocomposite are drastically affecting the muscular activity and exploratory behavior in male albino mice, while the studied behavioral tests, in general, remained unaffected in female albino mice.

The interactions between adenosine triphosphate-binding cassette (ABC) transporters and nano-sized materials are attracting increasing attention, due to their great potential in overcoming the multidrug resistance (MDR) phenomena in cancer treatment. However, the inner mechanisms involved in the interactions are largely unknown. In this study, two commercial quantum dots (QDs), CdSe/ZnS-MPA and CdSe/ZnS-GSH, were tested for their interactions with P-glycoprotein (P-gp), as well as the relating mechanisms in lung cancer (A549) cells. Both QDs significantly suppressed the gene and protein expressions of P-gp in A549 cells. To explain this, the gene expressions of nine relating microRNAs (miRNAs) were evaluated. The results indicated a shared up-regulation of miR-34b and miR-185 by both QDs. Furthermore, mimics and inhibitors of miR-34b and miR-185 significantly enhanced and suppressed the gene and protein expressions of P-gp, respectively, confirming the modulatory function of these two miRNAs on P-gp. Interestingly, expressions of both miRNAs were suppressed during treatment with Cd 2+ and doxorubicin, which induced the expression of P-gp, indicating the universality of these miRNAs-related mechanisms. Thus, as miR-34b and miR-185 participated in the suppression of P-gp functions in A549 cells they could be interesting targets for the treatment of lung cancer., (© 2019 John Wiley & Sons, Ltd.)

Although zinc is an essential element for organisms, excess zinc exposure is harmful. We assessed the possible negative influence of zinc (Zn) on the freshwater fish Danio rerio during its early life stage by using Organization for Economic Cooperation and Development test guideline no. 210. Lethality of Zn after hatching occurred in a concentration dependent manner. The LC 50 and lowest observed effect concentration of mortality values in the present toxicity assay were 2.31 mg/L (95% confidence limit: 1.81-3.05) and 1.5 mg/L, respectively. These values were close to the reported concentration recorded in aquatic environments. Growth inhibition was observed at 15 and 30 days post-hatching with Zn exposure of 1.5 mg/L. In general, the growth hormone (Gh)/insulin-like growth factor-I (Igf-1) axis is important for growth in fishes, and Zn exposure induced a significant reduction of igf-1 expression at the concentration that caused growth inhibition. These findings suggest that the observed growth inhibition was induced by the suppression of igf-1 expression. In addition, these results suggest that by examining gene expression on the Gh/Igf-1 axis, it may be possible to predict growth suppression by chemical exposure., Competing Interests: Declaration of competing interest The authors have no conflicts of interest related to this research., (Copyright © 2019. Published by Elsevier Inc.)

The excellent optical property and relatively low toxicity of CdTe/ZnS core/shell quantum dots (QDs) make them an advanced fluorescent probe in the application of biomedicines, particularly in neuroscience. Thus, it is important to evaluate the biosafety of CdTe/ZnS QDs on the central nervous system (CNS). Our previous studies have suggested that the high possibility of CdTe/ZnS QDs being transported into the brain across the blood-brain barrier resulted in microglial activation and a shift of glycometabolism, but their underlying mechanism remains unclear. In this study, when mice were injected intravenously with CdTe/ZnS QDs through tail veins, the microglial activation, polarized into both M1 phenotype and M2 phenotype, and the neuronal impairment were observed in the hippocampus. Meanwhile, the increased pro- and anti-inflammatory cytokines released from BV2 microglial cells treated with CdTe/ZnS QDs also indicated that QD exposure was capable of inducing microglial activation in vitro. We further demonstrated that the glycolytic shift from oxidative phosphorylation switching into aerobic glycolysis was required in the microglial activation into M1 phenotype induced by CdTe/ZnS QD treatment, which was mediated through the mTOR signaling pathway. The findings, taken together, provide a mechanistic insight regarding the CdTe/ZnS QDs inducing microglial activation and the role of the glycolytic shift in it., (© 2019 John Wiley & Sons, Ltd.)

Zinc is essential for almost all living organisms, since it serves as a crucial cofactor for transcription factors and enzymes. However, it is toxic to cell growth when present in excess. The present work aims to investigate the toxicity mechanisms induced by zinc stress in yeast cells. To this end, 108 yeast single-gene deletion mutants were identified sensitive to 6 mM ZnCl 2 through a genome-wide screen. These genes were predominantly related to the biological processes of vacuolar acidification and transport, polyphosphate metabolic process, cytosolic transport, the process utilizing autophagic mechanism. A result from the measurement of intracellular zinc content showed that 64 mutants accumulated higher intracellular zinc under zinc stress than the wild-type cells. We further measured the intracellular ROS (reactive oxygen species) levels of 108 zinc-sensitive mutants treated with 3 mM ZnCl 2 We showed that the intracellular ROS levels in 51 mutants were increased by high zinc stress, suggesting their possible involvement in regulating ROS homeostasis in response to high zinc. The results also revealed that excess zinc could generate oxidative damage and then activate the expression of several antioxidant defenses genes. Taken together, the data obtained indicated that excess zinc toxicity might be mainly due to the high intracellular zinc levels and ROS levels induced by zinc stress in yeast cells. Our current findings would provide a basis to understand the molecular mechanisms of zinc toxicity in yeast cells., (Copyright © 2020 Zhao et al.)

Peptide mimetic of nerve growth factor GK-2 in a dose of 1-2 mg/liter improves survival of cultured rat cerebellar granule neurons exposed to the cytotoxic effect of zinc ions, but has no protective effect against copper ion cytotoxicity. Experiments on cultured rat hippocampal slices demonstrated that GK-2 did not affect reactivity of pyramidal neurons and long-term potentiation in the hippocampal field CA1 and the probability of glutamate release from presynaptic terminals in the synapses of the CA3-CA1 fields. The results suggest that GK-2 does not affect the functional properties of synaptic transmission under normal conditions, but protects neurons from the toxic effects of zinc, which creates prerequisites for GK-12 use in the treatment of neurodegenerative diseases.

The exponential growth of nanotechnology has led to the production of large quantities of nanomaterials for numerous industrial, technological, agricultural, environmental, food and many other applications. However, this huge production has raised growing concerns about the adverse effects that the release of these nanomaterials may have on the environment and on living organisms. Regarding the effects of QDs on aquatic organisms, existing data is scarce and often contradictory. Thus, more information is needed to understand the mechanisms associated with the potential toxicity of these nanomaterials in the aquatic environment. The toxicity of QDs (ZnS and CdS) was evaluated in the freshwater fish Danio rerio . The fishes were exposed for seven days to different concentrations of QDs (10, 100 and 1000 µg/L) individually and combined. Oxidative stress enzymes (catalase, superoxide dismutase and glutathione S -transferase), lipid peroxidation, HSP70 and total ubiquitin were assessed. In general, results suggest low to moderate toxicity as shown by the increase in catalase activity and lipid peroxidation levels. The QDs (ZnS and CdS) appear to cause more adverse effects singly than when tested combined. However, LPO results suggest that exposure to CdS singly caused more oxidative stress in zebrafish than ZnS or when the two QDs were tested combined. Levels of Zn and Cd measured in fish tissues indicate that both elements were bioaccumulated by fish and the concentrations increased in tissues according to the concentrations tested. The increase in HSP70 measured in fish exposed to 100 µg ZnS-QDs/L may be associated with high levels of Zn determined in fish tissues. No significant changes were detected for total ubiquitin. More experiments should be performed to fully understand the effects of QDs exposure to aquatic biota.

The selective measurement of cellular pH at specific regions is significant for the in-depth study of cell functions and pathological processes. Herein, we combined our previously developed rhodamine B-labeled cell-penetrating peptide spirolactam derivative with quantum dots to create a ratiometric nanobiosensor for the simultaneous sensing and imaging of lysosomes and extracellular pH.

Quantum Dots (QDs) are becoming more prevalent in products used in our daily lives, such as TVs and laptops, due to their unique and tunable optical properties. The possibility of using QDs as fluorescent probes in applications, such as medical imaging, has been a topic of interest for some time, but their potential toxicity and long-term effects on the environment are not well understood. In the present study, we investigated the effects of yellow CdSe/ZnS-QDs on Saccharomyces cerevisiae . We utilized growth assays, RNA-seq, reactive oxygen species (ROS) detection assays, and cell wall stability experiments to investigate the potential toxic effects of CdSe/ZnS-QDs. We found CdSe/ZnS-QDs had no negative effects on cell viability; however, cell wall-compromised cells showed more sensitivity in the presence of 10 µg/mL CdSe/ZnS-QDs compared to non-treated cells. In CdSe/ZnS-treated and non-treated cells, no significant change in superoxide was detected, but according to our transcriptomic analysis, thousands of genes in CdSe/ZnS-treated cells became differentially expressed. Four significantly differentiated genes found, including FAF1 , SDA1 , DAN1 , and TIR1 , were validated by consistent results with RT-qPCR assays. Our transcriptome analysis led us to conclude that exposure of CdSe/ZnS-QDs on yeast significantly affected genes implicated in multiple cellular processes.

The present study focused on the bioaccumulation and cytotoxicities of Cd 2+ , CdSe quantum dots (QDs) and CdSe/ZnS QDs in Escherichia coli (E. coli, represents prokaryotic system) and Phanerochaete chrysosporium (P. chrysosporium, represents eukaryotic system), respectively. Two types of QDs were characterized by transmission electron microscopy (TEM) and dynamic light scattering. The inductively coupled plasma optical emission spectrometer results showed that the bioaccumulation amounts of CdSe QDs by E. coli and P. chrysosporium were larger than those of CdSe/ZnS QDs due to the smaller particle size and less negative surface charges of CdSe QDs. Confocal microscopy and TEM results showed that there was an interaction between QDs and cells, and QDs have entered into the cells eventually, leading to the change of cell morphology. Plasma membrane fluidities and membrane H + -ATPase activities of E. coli and P. chrysosporium decreased gradually with the increasing concentrations of Cd 2+ , CdSe and CdSe/ZnS QDs. Results of the cell viabilities and intracellular reactive oxygen species levels indicated that the induced cytotoxicities were decreased as follows: CdSe QDs > CdSe/ZnS QDs > Cd 2+ . These findings suggested that the cytotoxicity of QDs was not only attributed to their heavy metal components, but also related to their nanosize effects which could induce particle-specific toxicity. The above results offer valuable information for exploring the cytotoxicity mechanism of QDs in prokaryote and eukaryote., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Here we report a green synthesis of ZnSe quantum dots (QDs) in aqueous solution of polyampholyte chitosan derivative - N-(2-carboxyethyl)chitosan (CEC) with substitution degrees (DS) from 0.7 to 1.3 and molecular weight (MW) of 40 kDa and 150 kDa. We have shown that the maximum intensity of photoluminescence (PL) is exhibited by ZnSe QDs synthesized in solutions of CEC with DS 1 at Se:Zn molar ratio 1:2.5. The defect-related band was predominant in the PL spectra of ZnSe QDs obtained at room temperature; however, hydrothermal treatment at 80-150 °C during 1-2 h significantly increased contribution of exciton emission to the spectra. Cytotoxicity of ZnSe QDs was investigated by MTT assay using cancer cell lines SKOV-3; SkBr-3; PANC-1; Colon-26 and human embryonic kidney cell line HEK293. Cytotoxicity of ZnSe QDs did not depend on MW or DS of CEC but significantly depended on the cell line, being the lowest for normal human cells HEK293 and breast cancer cell line SKOV-3. The hydrothermally treated ZnSe QDs showed higher toxicity toward both normal and cancer cell lines. Since ZnSe QDs were toxic for most of the investigated cancer cell lines, they cannot be used as inert tracers for bioimaging, but can be promising for further investigation for anticancer therapy., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Size dependent cytotoxicity of ZnS nanoparticles (NPs) was investigated in Human embryonic kidney (HEK-293) cell lines by MTT assay. The cells were incubated with varying concentration of ZnS NPs of sizes 4 nm, 10 nm and 25 nm for 48 h under different (cell culture) media viscosity conditions. The results showed that the toxicity is decreased with the particle size while it is negatively correlated with the viscosity of the media. Theoretical calculations were performed, by assuming equivolume stress model and the same is explained with schematics. Similarly, the effect of particle size and shape on toxicity is explained based on the theoretical calculation of the stress. The calculations showed that out of the possible cellular entry mechanisms for the cubic or cage shaped NPs, the highest toxicity is predicted for the entry through the corners while the lowest toxicity is predicted for the entry through the faces. The experimental observations depicting the cytotoxicity as a function of the viscosity of cell culture media was also validated by stress calculations and are found to be consistent. Studies on size and shape dependence of semiconductor NPs like ZnS is rather scarce, while the role of viscosity of cell culture media on the cytotoxicity is being reported for the first time. In summary, the study indicates that the cytotoxicity is an integral function of size and shape of NPs, physical parameters of the cell culture media in addition to the post entry biochemical interactions with the host cell.

Purpose: Mn-doped ZnS quantum dots (QDs) with special luminescent properties have been widely researched and applied in various fields. Thus, their release toxicity and security cannot be ignored., Methods: In the present study, the toxicity and non-targeted metabolomics of Mn-doped ZnS QDs were investigated after single intravenous injection. Serum metabolites were evaluated based on gas chromatography-mass spectrometry together with multivariate statistical analyses [principal component analysis, partial least squares discriminant analysis, and orthogonal PLS-DA]., Results: The modified metabolites (variable importance in the projection (VIP) >1 and p <0.05) revealed that Mn-doped ZnS QDs exposure disturbed glycolysis, tricarboxylic acid cycle, ketoplasia, glutaminolysis, and amino acid and lipid metabolism. The behavior, coefficients of organs, and histological changes were the same as in the control group, and the disturbance of hematology and serum biochemistry was not dose- or time-dependent., Conclusion: Our study provides a general observation regarding the toxicity and potential metabolic responses of mice exposed to Mn-doped ZnS QDs., Competing Interests: The authors report no conflicts of interest in this work.

Zinc hydroxyfluoride (Zn(OH)F) sonocatalyst was prepared by using solvothermal method and was characterized by using various techniques. The sonocatalytic degradation of ampicillin (AMP) in water by sonolysis, bare ZnO and Zn(OH)F was investigated in terms of AMP removal, mineralization, detoxification of solution, and remaining by-products at the end of process. Results revealed that the sonocatalytic performance of Zn(OH)F was significantly greater than that of bare ZnO. Under the optimum conditions, the removal percentage of AMP by Zn(OH)F was ∼97% after 90 min reaction, while 51% and 36% COD and TOC removal were achieved after 120 min reaction, respectively. The study of Zn(OH)F stability revealed that the degradation efficiency of AMP was reduced by only 5% even after being reused for four experiments. The toxicity of initial and treated solutions was assessed by using agar-well diffusion method and ToxTrak ™ toxicity assay, and the results indicated a substantial reduction in the toxicity of solution after the treatment. The formation of some by-products during the sonolysis and sonocatalysis was evaluated by LC-HR-MS/MS method. LC-HR-MS/MS results showed that the concentration of most by-products, which were produced after 90 min treatment by US/Zn(OH)F process, was considerably lower than those obtained during sonolysis and US/ZnO processes., (Copyright © 2019. Published by Elsevier B.V.)