Co-exposure of zinc oxide nanoparticles and multi-layer graphenes in blackfish (Capoeta fusca): evaluation of lethal, behavioural, and histopathological effects.

Zinc oxide nanoparticles (ZnO NPs) and multi-layer graphenes (MLGs) are widely used, and due to the lack of appropriate wastewater treatment may end up in the aquatic environment, with unknown consequences to biota. The main purpose of this study was to assess the acute toxicity, histopathological and behavioural changes caused by the exposure of ZnO NPs and MLGs, alone and combined, to the blackfish Capoeta fusca. The estimated mean 96 h-LC50 for ZnO NPs was 4.9 mg L-1 and 68.4 mg L-1 for MLGs. In combination, MLGs increased the acute toxicity of the ZnO NPs. The effects of the different NPs on the gills included hyperplasia, aneurisms, and fusion of the lamellae. In the intestine, exposure to the NPs resulted in an increase in the number and swelling of goblet cells and tissue degeneration. Loss of balance, restlessness, erratic and abnormal swimming patterns were the most common behavioural changes seen in the ZnO NPs' exposed blackfish. In contrast with the acute toxicity findings, MLGs decreased the histopathological and behavioural effects of the ZnO NPs on both gills and intestinal tissues as well as fish behaviour. Our experimental results illustrated insights into the simultaneous exposure assessment of metal-based NPs and carbon nanomaterials, although further research is needed on the interactions exposure of these substances to interpreting the toxicological effects of metal-based nanomaterials seen in exposed organisms.

Waterborne outbreak in a rural area in Greece during the COVID-19 pandemic: contribution of community pharmacies.

INTRODUCTION: On 15 June 2020, the National Public Health Organization was informed about the identification of two cases of Escherichia coli Ο157 infection in a small town in the Peloponnese Region in Greece and we suspected an outbreak. METHODS: We asked the local pharmacist to assist us to verify the outbreak by providing the daily number of over-the-counter anti-diarrheal drugs sold from 20 May 2020 onwards. The pharmacist asked customers with gastroenteritis to submit stool samples at the local hospital. Samples were tested for 22 pathogens. We conducted a 1 : 1 case-control study. Cases and controls were retrieved from the pharmacy client list. Chlorination records of the water supply system were retrieved, and water samples were tested for microbiological indicators and viruses. RESULTS: The increased number of sales of anti-diarrheal drugs verified the outbreak. Overall, 58 cases and 57 controls were recruited for the study. Tap water consumption (odds ratio (OR)=10.9, 95% confidence interval (CI)=3.1-38.0, p<0.001) and consumption of ice cubes made from tap water (OR=39.3, 95%CI=10.3-150.9, p<0.001) were independently associated with gastroenteritis occurrence. Eleven stool samples were tested; one was positive for shigatoxin-producing E. coli, one for enteropathogenic E. coli, four for E. coli Ο157 and one for Salmonella spp. Four samples tested negative. Five water samples collected on 18 June tested negative. The residual chlorine on 5 and 14 June ranged from 0.12 mg/L to 0.14 mg/L. CONCLUSION: This was the first investigation of a waterborne outbreak in Greece performed with the collaboration of a local pharmacy. The COVID-19 pandemic favored the use of alternative resources and channels of communication with the local population, which can also be used in the future, especially in remote areas of the country.

Lysed Erythrocyte Membranes Promote Vascular Calcification.

BACKGROUND: Intraplaque hemorrhage promotes atherosclerosis progression, and erythrocytes may contribute to this process. In this study we examined the effects of red blood cells on smooth muscle cell mineralization and vascular calcification and the possible mechanisms involved. METHODS: Erythrocytes were isolated from human and murine whole blood. Intact and lysed erythrocytes and their membrane fraction or specific erythrocyte components were examined in vitro using diverse calcification assays, ex vivo by using the murine aortic ring calcification model, and in vivo after murine erythrocyte membrane injection into neointimal lesions of hypercholesterolemic apolipoprotein E-deficient mice. Vascular tissues (aortic valves, atherosclerotic carotid artery specimens, abdominal aortic aneurysms) were obtained from patients undergoing surgery. RESULTS: The membrane fraction of lysed, but not intact human erythrocytes promoted mineralization of human arterial smooth muscle cells in culture, as shown by Alizarin red and van Kossa stain and increased alkaline phosphatase activity, and by increased expression of osteoblast-specific transcription factors (eg, runt-related transcription factor 2, osterix) and differentiation markers (eg, osteopontin, osteocalcin, and osterix). Erythrocyte membranes dose-dependently enhanced calcification in murine aortic rings, and extravasated CD235a-positive erythrocytes or Perl iron-positive signals colocalized with calcified areas or osteoblast-like cells in human vascular lesions. Mechanistically, the osteoinductive activity of lysed erythrocytes was localized to their membrane fraction, did not involve membrane lipids, heme, or iron, and was enhanced after removal of the nitric oxide (NO) scavenger hemoglobin. Lysed erythrocyte membranes enhanced calcification to a similar extent as the NO donor diethylenetriamine-NO, and their osteoinductive effects could be further augmented by arginase-1 inhibition (indirectly increasing NO bioavailability). However, the osteoinductive effects of erythrocyte membranes were reduced in human arterial smooth muscle cells treated with the NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide or following inhibition of NO synthase or the NO receptor soluble guanylate cyclase. Erythrocytes isolated from endothelial NO synthase-deficient mice exhibited a reduced potency to promote calcification in the aortic ring assay and after injection into murine vascular lesions. CONCLUSIONS: Our findings in cells, genetically modified mice, and human vascular specimens suggest that intraplaque hemorrhage with erythrocyte extravasation and lysis promotes osteoblastic differentiation of smooth muscle cells and vascular lesion calcification, and also support a role for erythrocyte-derived NO.

Age-Dependent and -Independent Effects of Perivascular Adipose Tissue and Its Paracrine Activities during Neointima Formation.

Cardiovascular risk factors may act by modulating the composition and function of the adventitia. Here we examine how age affects perivascular adipose tissue (PVAT) and its paracrine activities during neointima formation. Aortic tissue and PVAT or primary aortic smooth muscle cells from male C57BL/6JRj mice aged 52 weeks ("middle-aged") were compared to tissue or cells from mice aged 16 weeks ("adult"). Vascular injury was induced at the carotid artery using 10% ferric chloride. Carotid arteries from the middle-aged mice exhibited smooth muscle de-differentiation and elevated senescence marker expression, and vascular injury further aggravated media and adventitia thickening. Perivascular transplantation of PVAT had no effect on these parameters, but age-independently reduced neointima formation and lumen stenosis. Quantitative PCR analysis revealed a blunted increase in senescence-associated proinflammatory changes in perivascular tissue compared to visceral adipose tissue and higher expression of mediators attenuating neointima formation. Elevated levels of protein inhibitor of activated STAT1 (PIAS1) and lower expression of STAT1- or NFκB-regulated genes involved in adipocyte differentiation, inflammation, and apoptosis/senescence were present in mouse PVAT, whereas PIAS1 was reduced in the PVAT of patients with atherosclerotic vessel disease. Our findings suggest that age affects adipose tissue and its paracrine vascular activities in a depot-specific manner. PIAS1 may mediate the age-independent vasculoprotective effects of perivascular fat.

Influence of environmental conditions on the toxicokinetics of cadmium in the marine copepod Acartia tonsa.

mMarine and estuarine ecosystems are highly productive areas that often act as a final sink for several pollutants, such as cadmium. Environmental conditions in these habitats can affect metal speciation, as well as its uptake and depuration by living organisms. The aim of this study was to assess cadmium uptake and depuration rates in the euryhaline calanoid copepod Acartia tonsa under different pH, salinity and temperature conditions. Cadmium speciation did not vary with changing pH or temperature, but varied with salinity. Free Cd2+ ion activity increased with decreasing salinities resulting in increased cadmium concentrations in A. tonsa. However, uptake rate, derived using free Cd2+ ion activity, showed no significant differences at different salinities indicating a simultaneous combined effect of Cd2+ speciation and metabolic rates for osmoregulation. Cadmium concentration in A. tonsa and uptake rate increased with increasing pH, showing a peak at the intermediate pH of 7.5, while depuration rate fluctuated, thus suggesting that both parameters are mediated by metabolic processes (to maintain homeostasis at pH levels lower than normal) and ion competition at membrane binding sites. Cadmium concentration in A. tonsa, uptake and depuration rates increased with increasing temperature, a trend that can be attributed to an increase in metabolic energy demand at higher temperatures. The present study shows that cadmium uptake and depuration rates in the marine copepod A. tonsa is mostly affected by biological processes, mainly driven by metabolic mechanisms, and to a lesser extent by metal speciation in the exposure medium.

Investigating the structure and dynamics of the PIK3CA wild-type and H1047R oncogenic mutant.

The PIK3CA gene is one of the most frequently mutated oncogenes in human cancers. It encodes p110α, the catalytic subunit of phosphatidylinositol 3-kinase alpha (PI3Kα), which activates signaling cascades leading to cell proliferation, survival, and cell growth. The most frequent mutation in PIK3CA is H1047R, which results in enzymatic overactivation. Understanding how the H1047R mutation causes the enhanced activity of the protein in atomic detail is central to developing mutant-specific therapeutics for cancer. To this end, Surface Plasmon Resonance (SPR) experiments and Molecular Dynamics (MD) simulations were carried out for both wild-type (WT) and H1047R mutant proteins. An expanded positive charge distribution on the membrane binding regions of the mutant with respect to the WT protein is observed through MD simulations, which justifies the increased ability of the mutated protein variant to bind to membranes rich in anionic lipids in our SPR experiments. Our results further support an auto-inhibitory role of the C-terminal tail in the WT protein, which is abolished in the mutant protein due to loss of crucial intermolecular interactions. Moreover, Functional Mode Analysis reveals that the H1047R mutation alters the twisting motion of the N-lobe of the kinase domain with respect to the C-lobe and shifts the position of the conserved P-loop residues in the vicinity of the active site. These findings demonstrate the dynamical and structural differences of the two proteins in atomic detail and propose a mechanism of overactivation for the mutant protein. The results may be further utilized for the design of mutant-specific PI3Kα inhibitors that exploit the altered mutant conformation.

Endocrine disruption effects of p,p'-DDE on juvenile zebrafish.

The persistent organic pollutant p,p'-DDE, the major metabolite of the insecticide DDT, has displayed evidence of endocrine disruption through the inhibition of androgen binding to androgen receptors in different species. Although p,p'-DDE was continuously detected in wild fish with abnormal gonad development such as intersex, little is known about its mode of action during gonad development in fish. To elucidate the potential endocrine effects of this pollutant in zebrafish (Danio rerio), juveniles (30 days post hatch) were exposed to p,p'-DDE during the critical window of sexual differentiation. Fish were exposed to sublethal concentrations ranging from 0.01 to 20 µg l(-1) over 14 days and were maintained in control water for an additional 4 months. As core endpoints, the vitellogenin (vtg) concentration was measured at the end of exposure, and sex ratio and the gonadosomatic index were assessed 4 months after the end of exposure. An increase in vtg production in whole body homogenate was observed in fish exposed to 0.2 and 2.0 µg l(-1) p,p'-DDE. No significant differences were displayed in morphological parameters such as the gonadosomatic index of males and females or sex ratio. However, exposed females presented histopathological changes that include the reduction of the number of mature oocytes, which might impair their successful reproduction. These results demonstrate the ability of p,p'-DDE to cause endocrine disruption in zebrafish exposed during gonad differentiation of juvenile specimens. Furthermore, vtg induction by p,p'-DDE in juvenile zebrafish arises as a predictive marker for adverse effects of this DDT metabolite on the ovarian function of female zebrafish.

Early changes of the kinetics of monocyte trem-1 reflect final outcome in human sepsis.

BACKGROUND: TREM-1 (triggering receptor expressed on myeloid cells), a receptor expressed on neutrophils and monocytes, is upregulated in sepsis and seems to tune the inflammatory response. We explored the expression of TREM-1 at the gene level and on cell membranes of monocytes and association with clinical outcome. METHODS: Peripheral venous blood was sampled from 75 septic patients (39 patients with sepsis, 25 with severe sepsis and 11 with septic shock) on sepsis days 1, 3 and 7. TREM-1 on monocytes was measured by flow cytometry; gene expression of TREM-1 in circulating mononuclear cells was assessed by real-time PCR. sTREM-1 was measured in serum by an enzyme immunoassay. RESULTS: Although surface TREM-1, sTREM-1 and TREM-1 gene expression did not differ between sepsis, severe sepsis and septic shock on day 1, survivors had greater expression of surface TREM-1 on days 3 and 7 compared to non-survivors. sTREM-1 on non-survivors decreased on day 3 compared to baseline. Patients with increase of monocyte gene expression of TREM-1 from day 1 to day 3 had prolonged survival compared to patients with decrease of gene expression of TREM-1 from day 1 to day 3 (p: 0.031). CONCLUSIONS: Early decrease of gene expression of TREM-1 in monocytes is associated with poor outcome. A reciprocal decrease of the pro-inflammatory surface receptor TREM-1 linked with sepsis-induced immunosuppression may be part of the explanation.

Changes of chemical chronic toxicity to Daphnia magna under different food regimes.

In aquatic ecosystems several stressors may act together and affect the life traits of organisms. Pesticide runoffs are usually associated with high inputs of organic matter and depletion of oxygen in aquatic systems. This study aimed at combining anthropogenic stress (chemicals) and natural stress (food availability) and evaluates their joint effect to the life traits of Daphnia magna. The neonicotinoid insecticide imidacloprid and the heavy metal nickel chloride were used and a 21 d chronic test was carried out to obtain reproduction and growth data. The conceptual model Independent action, usually used for assessing response patterns in chemical mixtures, was used for data interpretation. Results showed an increase in the reproduction and growth pattern of D. magna as food levels increased. Both chemicals significantly impaired the reproduction as well as the somatic growth of the organism while the same happened with food concentrations lower than 3×10(5) cells/mL. It was also observed that food availability did not change the toxicity of imidacloprid and nickel chloride when food levels were higher than 3×10(5) cells/mL. When combined with low food levels, imidacloprid showed a slight increase in toxicity, showing that daphnids become more sensitive with reduced food availability, however in a non-significant way. However, toxicity of nickel appeared to be independent of the food level. Both chemicals induced mortality to the organisms exposed in the absence of food only at the end of the test.

Evidence That a Peptide-Drug/p53 Gene Complex Promotes Cognate Gene Expression and Inhibits the Viability of Glioblastoma Cells.

Glioblastoma multiform (GBM) is considered the deadliest brain cancer. Conventional therapies are followed by poor patient survival outcomes, so novel and more efficacious therapeutic strategies are imperative to tackle this scourge. Gene therapy has emerged as an exciting and innovative tool in cancer therapy. Its combination with chemotherapy has significantly improved therapeutic outcomes. In line with this, our team has developed temozolomide-transferrin (Tf) peptide (WRAP5)/p53 gene nanometric complexes that were revealed to be biocompatible with non-cancerous cells and in a zebrafish model and were able to efficiently target and internalize into SNB19 and U373 glioma cell lines. The transfection of these cells, mediated by the formulated peptide-drug/gene complexes, resulted in p53 expression. The combined action of the anticancer drug with p53 supplementation in cancer cells enhances cytotoxicity, which was correlated to apoptosis activation through quantification of caspase-3 activity. In addition, increased caspase-9 levels revealed that the intrinsic or mitochondrial pathway of apoptosis was implicated. This assumption was further evidenced by the presence, in glioma cells, of Bax protein overexpression-a core regulator of this apoptotic pathway. Our findings demonstrated the great potential of peptide TMZ/p53 co-delivery complexes for cellular transfection, p53 expression, and apoptosis induction, holding promising therapeutic value toward glioblastoma.

Responses of soil microbiome to copper-based materials (nano and bulk) for agricultural applications: An indoor-mesocosm experiment.

The foreseen increasing application of copper-based nanomaterials (Cu-NMs), replacing or complementing existing Cu-agrochemicals, may negatively impact the soil microbiome. Thus, we studied the effects on soil microbiome function and composition of nano copper oxide (nCuO) or copper hydroxide NMs in a commercial (Kocide®3000) or a lab-synthetized formulation (nCu(OH)2) or bulk copper hydroxide (Cu(OH)2-B), at the commonly recommended Cu dose of 50 mg(Cu)kg-1 soil. Microbial responses were studied over 28 days in a designed indoor mesocosm. On day-28, in comparison to non-treated soil (CT), all Cu-treatments led to a reduction in dehydrogenase (95% to 68%), arylsulfatase (41% to 27%), and urease (40% to 20%) activity. There was a 32% increase in the utilization of carbon substrates in the nCuO-treatment and an increased abundance of viable bacteria in the nCu(OH)2-treatment (75% of heterotrophic and 69% of P-solubilizing bacteria). The relative abundance of Acidobacteria [Kocide®3000, nCuO, and Cu(OH)2-B treatments] and Flavobacteriia [nCu(OH)2-treatment] was negatively affected by Cu exposure. The abundance of Cu-tolerant bacteria increased in soils treated with Kocide®3000 (Clostridia) and nCu(OH)2 (Gemmatimonadetes). All Cu-treated soils exhibited a reduced abundance of denitrification-related genes (0.05% of nosZ gene). The DTPA-extractable pool of ionic Cu(II) varied among treatments: Cu(OH)2-B > Kocide®3000 âˆ¼ nCuO>nCu(OH)2, which may explain changes on the soil microbiome composition, at the genera and OTU levels. Thus, our study revealed that Cu-materials (nano and bulk) influence the soil microbiome with implications on its ecological role. It highlights the importance of assessing the impact of Cu-materials under dynamic and complex exposure scenarios and emphasizes the need for specific regulatory frameworks for NMs.

Radiotherapy in Uveal Melanoma: A Review of Ocular Complications.

Uveal melanoma represents the most prevalent form of primary malignant intraocular tumor in adults. Historically, enucleation was considered the gold-standard approach in the treatment of uveal melanoma. Currently, radiotherapy is the most commonly used therapy, aiming at a better quality of life. However, radiotherapy can result in several ocular complications, some of which may be vision-threatening. Radiation-induced dry eye, scleral necrosis, cataract, rubeosis iridis, neovascular glaucoma, radiation retinopathy, maculopathy, and optic neuropathy are the most common complications. This article aims to summarize the current literature regarding the ocular complications after radiotherapy, as well as their clinical features, risk factors, and management strategies. A thorough understanding of these issues is crucial for ophthalmologists and oncologists to provide optimal patient care, improve visual outcomes, and minimize long-term complications.

A Systematic Review of Nano- and Microplastic (NMP) Influence on the Bioaccumulation of Environmental Contaminants: Part I-Soil Organisms.

Nano- and microplastics (NMPs) are a group of contaminants that cause concern due to their abundance in the environment, high persistence, and interaction with other contaminants. This review aims to understand the role of NMP in the bioaccumulation of environmental contaminants. For that, a comprehensive literature search was conducted to identify publications that compared the uptake of contaminants in the presence and absence of NMP. In this part I, twenty-eight publications of the terrestrial compartment were analyzed. Two main taxonomic groups were studied, namely, earthworms and terrestrial plants. In earthworms, most studies observed an increase in the bioaccumulation of the contaminants, while in plants, most studies observed a decrease in the bioaccumulation. Changes in bioavailable fractions of contaminants due to NMP presence was the main reason pointed out by the authors for their outcomes. Moreover, biological aspects were also found to be important in defining how NMPs affect bioaccumulation. Dermal damage and changes in contaminant-degrading bacteria in the gut of earthworms caused an increase in bioaccumulation, and root pore blockage was a common reason for the decrease in the bioaccumulation of contaminants in plants. Nevertheless, such effects were mainly observed at high, unrealistic NMP concentrations. Finally, knowledge gaps were identified, and the limitations of this systematic review were presented.

Zn-Al layered double hydroxides induce embryo malformations and impair locomotion behavior in Danio rerio.

Layered double hydroxides (LDHs) are stimuli-responsive anionic nanoclays. The vast possibilities of using LDHs can lead to their existence in the ecosystem, raising a question of potential ecological concern. However, little is known about the effect of these nanomaterials on freshwater organisms. The present study aimed to assess the ecotoxicological effects of Zinc-Aluminium LDH-nitrate (ZnAl LDH-NO3) in zebrafish (Danio rerio) early life stages. The endpoints measured were mortality, malformations and hatching rate after exposure of D. rerio embryos and larvae to ZnAl LDH-NO3 following the OECD 236 guideline. The behavioral, biochemical (markers of oxidative stress and neurotoxicity), and molecular (at DNA level) alterations were also assessed using sub-lethal concentrations. No observable acute effects were detected up to 415.2 mg LDH/L while the 96 h-LC50 was estimated as 559.9 mg/L. Tested LDH caused malformations in D. rerio embryos, such as pericardial edema, incomplete yolk sac absorption and tail deformities (96 h-EC50 = 172.4 mg/L). During the dark periods, the locomotor behavior in zebrafish larvae was affected upon ZnAl LDH-NO3 exposure. However, no significant biochemical and molecular changes were recorded. The present findings suggest that ZnAl LDH-NO3 can be regarded as a non-toxic nanomaterial towards D. rerio (E/LC50 > > 100 mg/L) although impairment of the locomotion behavior on zebrafish embryos can be expected at concentrations below 100 mg/L.

Systematic Review of Nano- and Microplastics' (NMP) Influence on the Bioaccumulation of Environmental Contaminants: Part II-Freshwater Organisms.

Nano- and microplastic fragments (NMPs) exist ubiquitously in all environmental compartments. The literature-based evidence suggests that NMPs interact with other environmental contaminants in freshwater ecosystems through sorption mechanisms, thereby playing a vector role. Chemically bound NMPs can translocate throughout the environment, reaching long distances from the contaminant discharge site. In addition, they can be ab/adsorbed by freshwater organisms. Although many studies show that NMPs can increase toxicity towards freshwater biota through the carrier role, little is known regarding their potential to influence the bioaccumulation of environmental contaminants (EC) in freshwater species. This review is part II of a systematic literature review regarding the influence of NMPs on bioaccumulation. Part I deals with terrestrial organisms and part II is devoted to freshwater organisms. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA ScR) was used for the literature search and selection. Only studies that assessed the bioaccumulation of EC in the presence of NMPs and compared this with the bioaccumulation of the isolated EC were considered. Here, we discuss the outcome of 46 papers, considering NMPs that induced an increase, induced a decrease, or caused no effect on bioaccumulation. Lastly, knowledge gaps are identified, and future directives for this area of research are discussed.

Assessing the impact of antineoplastic drugs in the aquatic environment: State of the art and future perspective for freshwater organisms.

Since the late 70s, the continuous pharmaceuticals` input into the environment has raised concerns regarding the eventual risk posed by such compounds to human and environmental health. A major group of pharmaceuticals in terms of environmental impact are the antineoplastic agents (AAs). Herein, we followed a systematic review method to retrieve antineoplastic agents (AAs') ecotoxicological information regarding freshwater species. In this analysis, data from diverse taxonomic groups, from microorganisms to vertebrate species, looked at different levels of biological organization, including cell lines. Furthermore, this review gathers ecotoxicological parameters (EC50 and LC50) for imatinib (IM), cisplatin (CisPt), and 5-fluorouracil (5-FU) in species sensitivity distribution (SSD) curves and estimates the hazard concentration (HC5) considering the protection of 95% of the ecological community. Lastly, we suggest how we can improve AAs' Environmental Risk Assessment (ERA), considering potential adoptable toxicity endpoints, test duration, AAs metabolites testing, and AAs mixture exposure.

Unveiling the molecular mechanisms and developmental consequences of mercury (Hg) toxicity in zebrafish embryo-larvae: A comprehensive approach.

Mercury (Hg) is a global contaminant affecting aquatic ecosystems' health. Chronic exposure to Hg has shown that the normal development of zebrafish embryo-larvae is affected. However, the molecular mechanisms behind the toxicity of Hg on fish embryonic development are still poorly understood. This work aimed to investigate the effects of Hg exposure on zebrafish embryo-larvae using a combined approach at individual (mortality, embryo development and locomotor behavior) and biochemical (neurotoxicity and oxidative stress enzymatic activities and protein phosphatase expression) levels. The Fish Embryo Toxicity assay followed the Organization for Economic Cooperation and Development Guideline 236 and used a concentration range between 13 and 401 µg Hg/L. Lethal and developmental endpoints were examined at 24, 48, 72 and 96 hpf. Biochemical markers, including Acetylcholinesterase (AChE), Catalase (CAT), Glutathione Reductase (GR), and Glutathione-S-Transferase (GST) activities and, for the first time, the expression of the protein phosphatase 1 gamma (PP1γ) was assessed after 24, 48, 72 and 96 h of exposure to 10 and 100 µg Hg/L. The behavioral effects of a sublethal range of Hg (from 0.8 to 13 µg Hg/L) were assessed using an automated video tracking system at 120 hpf. Several developmental abnormalities on zebrafish embryos and larvae, including pericardial edema, spin and tail deformities and reduced rate of consumption of the yolk sac, were found after exposure to Hg (LC50 at 96 hpf of 139 µg Hg/L) with EC50 values for total malformations ranging from 22 to 264 µg Hg/L. After 96 hpf, no significant effects were observed in the CAT and GR activities. However, an increase in the GST activity in a concentration and time-dependent manner was found, denoting possible stress-related adaptation of zebrafish embryos to deleterious effects of Hg exposure. The AchE activity showed a response pattern in line with the behavioral responses. At the lowest concentration tested, no significant effects were found for the AChE activity, whereas a decrease in AChE activity was observed at 100 µg Hg/L, suggesting that exposure to Hg induced neurotoxic effects in zebrafish embryos which in turn may explain the lack of equilibrium found in this study (EC50 at 96 hpf of 83 µg Hg/L). Moreover, a decrease in the PP1γ expression was found after 96 h of exposure to 10 and 100 µg Hg/L. Thus, we suggest that Hg may be an inhibitor of PP1γ in zebrafish embryos-larvae and thus, along with the alterations in the enzymatic activity of GST, explain some of the developmental malformations observed, as well as the lack of equilibrium. Hence, in this study, we propose the use of PP1 expression, in combination with apical and biochemical endpoints, as a precursor for assessing Hg's toxic mechanism on embryonic development.

Environmental Hazard of Anticancer Drugs: State of the Art and Future Perspective for Marine Organisms.

Pharmaceutical compounds represent a class of emerging contaminants present in the environment. Their intense (and increasing) use in human and veterinary medicine leads to their discharge, mainly via human excretion, into wastewater treatment plants where their removal is inefficient. A specific class of pharmaceuticals used to fight cancer, known as antineoplastic or anticancer drugs, has gained increased attention regarding their possible environmental hazard due to their pharmacological properties, which include the nonselective targeting of DNA replication mechanisms and cell division processes, potentially inducing cell apoptosis. To date, there is limited information concerning the effects of anticancer drugs and/or their metabolites in species inhabiting freshwater environments, let alone marine and estuarine compartments. In the present review, we aimed to assemble information regarding the impact that anticancer drugs have on biological traits of marine species, to identify gaps in the current environmental hazard assessment, and to make recommendations to promote an efficient environmental hazard assessment of anticancer drugs in the marine environment. Environ Toxicol Chem 2022;41:1793-1807. © 2022 SETAC.

Terrestrial organisms react differently to nano and non-nano Cu(OH)2 forms.

The application of nanomaterials in agriculture is deemed as a promising strategy to increase the sector's sustainability. Nanopesticides are expected to improve solutions for pest/disease management, while reducing adverse effects to ecosystems, in accordance with the European Green Deal strategy. Hitherto, nanopesticide research has mostly focused on assessing effects to target species or crops, and less attention has been devoted to non-target soil species. In this study, we explored whether three copper hydroxide-based forms (nano and non-nano) show different toxicity and accumulation patterns in two terrestrial invertebrates, the isopod Porcellionides pruinosus and the mealworm larvae Tenebrio molitor. Toxicity and bioaccumulation experiments were performed and time-course toxicity and toxicokinetics analyzed and modelled. We found important differences in copper sensitivity and accumulation: T. molitor was more resistant and able to eliminate copper compared to P. pruinosus. The nanopesticide mostly elicited lower effects for both species. Slower toxicokinetics by the nanopesticide and lower bioaccumulative potential to P. pruinosus must be partially responsible for the differences in toxicity. Although no toxicokinetics differences were found in T. molitor between Cu forms, distinct negative effects on growth must reflect different energetic costs for copper regulation. Even though effects on toxicity and bioaccumulation are species-specific, copper hydroxide-based nanopesticides may cause less adverse effects to soil organisms than conventional products, being a good solution for reducing the environmental impact. CAPSULE: Copper hydroxide-based nanopesticide was less toxic and bioaccumulative to soil organisms than conventional copper hydroxide products, being a good solution for reducing the environmental impact.