Polypseudorotaxane structure and polydopamine bond-based crosslinked hyaluronic acid (HA) hydrogels including donepezil-loaded microspheres were developed for subcutaneous injection. Both dopamine ...and polyethylene glycol (PEG) were covalently bonded to the HA polymer for catechol polymerization and inclusion complexation with alpha-cyclodextrin (α-CD), respectively. A PEG chain of HA-dopamine-PEG (HD-PEG) conjugate was threaded with α-CD to make a polypseudorotaxane structure and its pH was adjusted to 8.5 for dopamine polymerization. Poly(lactic-co-glycolic acid) (PLGA)/donepezil microsphere (PDM) was embedded into the HD-PEG network for its sustained release. The HD-PEG/α-CD/PDM 8.5 hydrogel system exhibited an immediate gelation pattern, injectability through single syringe, self-healing ability, and shear-thinning behavior. Donepezil was released from the HD-PEG/α-CD/PDM 8.5 hydrogel in a sustained pattern. Following subcutaneous injection, the weight of excised HD-PEG/α-CD/PDM 8.5 hydrogel was higher than the other groups on day 14. These findings support the clinical feasibility of the HD-PEG/α-CD/PDM 8.5 hydrogel for subcutaneous injection.
•Hyaluronic acid-dopamine-polyethylene glycol (HD-PEG) was synthesized and identified.•HD-PEG was threaded with alpha-cyclodextrin (α-CD) and pH was adjusted to 8.5.•Polypseudorotaxane structure and polydopamine bond-based hydrogel was fabricated.•Donepezil-loaded microspheres were embedded in hydrogel system for sustained release.•Rheological features of injectable hydrogel were tuned for slow biodegradation.
The toxicity of perfluorinated surfactants perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorobutane sulfonate (PFBS) and PF-656 as well as the sulfosuccinate surfactant ...docusate sodium has been examined using two bioluminescence inhibition assays based on the marine bacterium
Vibrio fischeri and the self-luminescent cyanobacterial recombinant strain
Anabaena CPB4337. We also determined multigenerational toxicity towards the growth of the algae
Pseudokirchneriella subcapitata. With
EC
50 values in the 43–75
mg/L range, docusate sodium exhibited a higher toxicity towards the three organisms than PFOS, PFOA, PF-656 and PFBS. We investigated the toxicological interactions of the most toxic surfactant, docusate sodium, with two chlorinated compounds, triclosan and 2,4,6-trichlorophenol (TCP), in their binary and ternary mixtures using the method of the combination index based on the median-effect equation. In general, the binary mixture of the chlorinated compounds triclosan and TCP exhibited antagonism, which was stronger for the growth test using
P. subcapitata. Except for the green alga, the binary mixtures of docusate sodium with TCP or triclosan showed synergism at medium to high effect levels; the synergistic behaviour predominating in the ternary mixture and in the three tested species. This result highlights the potential toxicological risk associated with the co-occurrence of this surfactant with other pollutants.
The individual and combined toxicities of amoxicillin, erythromycin, levofloxacin, norfloxacin and tetracycline have been examined in two organisms representative of the aquatic environment, the ...cyanobacterium Anabaena CPB4337 as a target organism and the green alga Pseudokirchneriella subcapitata as a non-target organism. The cyanobacterium was more sensitive than the green alga to the toxic effect of antibiotics. Erythromycin was highly toxic for both organisms; tetracycline was more toxic to the green algae whereas the quinolones levofloxacin and norfloxacin were more toxic to the cyanobacterium than to the green alga. Amoxicillin also displayed toxicity to the cyanobacterium but showed no toxicity to the green alga. The toxicological interactions of antibiotics in the whole range of effect levels either in binary or multicomponent mixtures were analyzed using the Combination Index (CI) method. In most cases, synergism clearly predominated both for the green alga and the cyanobacterium. The CI method was compared with the classical models of additivity Concentration Addition (CA) and Independent Action (IA) finding that CI could accurately predict deviations from additivity. Risk assessment was performed by calculating the ratio between Measured Environmental Concentration (MEC) and the Predicted No Effect Concentration (PNEC). A MEC/PNEC ratio higher than 1 was found for the binary erythromycin and tetracycline mixture in wastewater effluents, a combination which showed a strong synergism at low effect levels in both organisms. From the tested antibiotic mixtures, it can be concluded that certain specific combinations may pose a potential ecological risk for aquatic ecosystems with the present environmentally measured concentrations.
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► The cyanobacterium was more sensitive than the green alga to antibiotic toxicity. ► Erythromycin was highly toxic for both aquatic organisms. ► Synergism was the predominant antibiotic interaction in both organisms. ► The erythromycin–tetracycline combination poses an ecological risk.
•Acute, semi-field and field toxicity of pesticides to Apis cerana &A. mellifera studied.•Chlorpyripos, dichlorvos, malathion, profenofos, monocrotophos & deltamethrin caused 100% ...mortality.•Acetamiprid and endosulfan were safer to both the bees in filter paper and topical bioassays.•In second tier, monocrotophos, thiamethoxam, dichlorvos, profenofos and chlorpyriphos are highly toxic.•Acetamiprid and endosulfan did not cause any repellent effect on honey bees in the field trials.
A series of experiments were carried out to determine the acute toxicity of pesticides in the laboratory, toxicity through spray on flowering plants of mustard (Tier II evaluation) and field on both Apis cerana and A. mellifera bees. The overall mortality of honey bees through topical (direct contact) were found significantly higher than that of indirect filter paper contamination assays. Insecticides viz., chlorpyriphos, dichlorvos, malathion, profenofos, monocrotophos and deltamethrin when exposed directly or indirectly at their field recommended doses caused very high mortality up to 100% to both the bees at 48 HAT. The insecticides that caused less mortality through filter paper contamination viz., flubendiamide, methyl demeton, imidacloprid and thiamethoxam caused very high morality through direct exposure. Apart from all the fungicides tested, carbendazim, mancozeb, chlorothalonil and propiconazole, insecticides acetamiprid and endosulfan were found safer to both the bees either by direct or indirect exposures. Tier II evaluation by spray of pesticides at their field recommended doses on potted mustard plants showed monocrotophos as the highly toxic insecticide with 100% mortality even with 1h of exposure followed by thiamethoxam, dichlorvos, profenofos and chlorpyriphos which are not to be recommended for use in pollinator attractive flowering plants. Acetamiprid and endosulfan did not cause any repellent effect on honey bees in the field trials endorse the usage of acetamiprid against sucking pest in flowering plants.
In this study, the microbial toxicities of metal oxide nanoparticles were evaluated for Escherichia coli, Bacillus subtilis, and Streptococcus aureus in laboratory experiments. The nanoparticles ...tested were CuO, NiO, ZnO, and Sb2O3. The metal oxide nanoparticles were dispersed thoroughly in a culture medium, and the microorganisms were cultivated on Luria–Bertani agar plates containing different concentrations of metal oxide nanoparticles. The bacteria were counted in terms of colony forming units (CFU). The CFU was reduced in a culture medium containing metal oxide NP, and the dose–response relationship was characterized. CuO nanoparticles were found to be the most toxic among the tested nanoparticles, followed by ZnO (except S. aureus), NiO, and Sb2O3 nanoparticles. We determined that the intrinsic toxic properties of heavy metals are also associated with the toxicity of metal oxide nanoparticles. Ion toxicity was also evaluated to determine the effects of metal ions dissolved from metal oxide NPs, and the toxicity induced from the dissolved ions was determined to be negligible herein. To the best of our knowledge, this is the first study of the toxicity of NiO and Sb2O3 NPs on microorganisms. We also discuss the implications of our findings regarding the effects of the intrinsic toxic properties of heavy metals, and concluded that the apparent toxicities of metal oxide NPs can largely be understood as a matter of particle toxicity.
►We evaluated the microbial toxicities of metal oxide nanoparticles for Escherichia coli, Bacillus subtilis, and Streptococcus aureus. ►Test nanoparticles were CuO, NiO, Z nO, and Sb2O3. ►CuO nanoparticles were the most toxic among the tested nanoparticles. ►The toxicity ranking of metal oxide nanoparticles was associated with the intrinsic toxic properties of heavy metals.
Multiple pesticides originating from plant protection treatments and the treatment of pests infecting honey bees are frequently detected in beehive matrices. Therefore, winter honey bees, which have ...a long life span, could be exposed to these pesticides for longer periods than summer honey bees. In this study, winter honey bees were exposed through food to the insecticide imidacloprid, the fungicide difenoconazole and the herbicide glyphosate, alone or in binary and ternary mixtures, at environmental concentrations (0 (controls), 0.1, 1 and 10 μg/L) for 20 days. The survival of the honey bees was significantly reduced after exposure to these 3 pesticides individually and in combination. Overall, the combinations had a higher impact than the pesticides alone with a maximum mortality of 52.9% after 20 days of exposure to the insecticide-fungicide binary mixture at 1 μg/L. The analyses of the surviving bees showed that these different pesticide combinations had a systemic global impact on the physiological state of the honey bees, as revealed by the modulation of head, midgut and abdomen glutathione-S-transferase, head acetylcholinesterase, abdomen glucose-6-phosphate dehydrogenase and midgut alkaline phosphatase, which are involved in the detoxification of xenobiotics, the nervous system, defenses against oxidative stress, metabolism and immunity, respectively. These results demonstrate the importance of studying the effects of chemical cocktails based on low realistic exposure levels and developing long-term tests to reveal possible lethal and adverse sublethal interactions in honey bees and other insect pollinators.
•Pesticide combinations are more toxic to honeybees than individual pesticides.•Increased concentrations of pesticides are not always linked to increased toxicity.•Pesticides modulate feeding behavior through an increase in food consumption.•Pesticides individually or in combination induce strong physiological perturbations.•The response to exposure to pesticides is systemic and tissue-specific.
Succinate dehydrogenase inhibitor (SDHI) fungicides are increasingly used in agriculture to combat molds and fungi, two major threats to both food supply and public health. However, the essential ...requirement for the succinate dehydrogenase (SDH) complex-the molecular target of SDHIs-in energy metabolism for almost all extant eukaryotes and the lack of species specificity of these fungicides raise concerns about their toxicity toward off-target organisms and, more generally, toward the environment. Herein we review the current knowledge on the toxicity toward zebrafish (
) of nine commonly used SDHI fungicides: bixafen, boscalid, fluxapyroxad, flutolanil, isoflucypram, isopyrazam, penthiopyrad, sedaxane, and thifluzamide. The results indicate that these SDHIs cause multiple adverse effects in embryos, larvae/juveniles, and/or adults, sometimes at developmentally relevant concentrations. Adverse effects include developmental toxicity, cardiovascular abnormalities, liver and kidney damage, oxidative stress, energy deficits, changes in metabolism, microcephaly, axon growth defects, apoptosis, and transcriptome changes, suggesting that glycometabolism deficit, oxidative stress, and apoptosis are critical in the toxicity of most of these SDHIs. However, other adverse outcome pathways, possibly involving unsuspected molecular targets, are also suggested. Lastly, we note that because of their recent arrival on the market, the number of studies addressing the toxicity of these compounds is still scant, emphasizing the need to further investigate the toxicity of all SDHIs currently used and to identify their adverse effects and associated modes of action, both alone and in combination with other pesticides.
Biochar and organic compost are widely used in agricultural soil remediation as soil immobilization agents. However, the effects of biochar and compost on microbial community assembly processes in ...polluted soil under freezingthawing need to be further clarified. Therefore, a freezethaw cycle experiment was conducted with glyphosate (herbicide), imidacloprid (insecticide) and pyraclostrobin (fungicide) polluted to understand the effect of biochar and compost on microbial community assembly and metabolic behavior. We found that biochar and compost could significantly promote the degradation of glyphosate, imidacloprid and pyraclostrobin in freezethaw soil decrease the half-life of the three pesticides. The addition of immobilization agents improved soil bacterial and fungal communities and promoted the transformation from homogeneous dispersal to homogeneous selection. For soil metabolism, the combined addition of biochar and compost alleviated the pollution of glyphosate, imidacloprid and imidacloprid to soil through up-regulation of metabolites (DEMs) in amino acid metabolism pathway and down-regulation of DEMs in fatty acid metabolism pathway. The structural equation modeling (SEM) results showed that soil pH and DOC were the main driving factors affecting microbial community assembly and metabolites. In summary, the combined addition of biochar and compost reduced the adverse effects of pesticides residues.
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•Biochar and compost promoted degradation of three pesticides in freezethaw soil.•Biochar and compost changed the microbial community assembly processes of soil.•Biochar and compost changed microbial metabolism in soil under freeze-thaw cycles.•Soil pH and DOC were the main driving factors of microbial assembly processes.
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