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The occurrence and risk of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q), derived from the oxidation of the tire antidegradant 6PPD, has raised significant concern since it was found to cause acute mortality in coho salmon when exposed to urban runoff. Given the short half-life period and low solubility of 6PPD-Q, reliable in situ measurement techniques are required to accurately understand its occurrence and behaviour in aquatic environments. Here, using the diffusive gradients in thin-films (DGT) method with HLB as a binding agent, we developed a new methodology to measure 6PPD-Q in urban waters. 6PPD-Q was rapidly and strongly adsorbed on the HLB-binding gel and was efficiently extracted using organic solvents. The HLB-DGT accumulated 6PPD-Q linearly for >7 d and its performance was not significantly affected by pH (6.5-8.5), ionic strength (0.0001-0.5 M) or dissolved organic matter (0-20 mg L-1). Field evaluation of the DGT method demonstrated its effectiveness in urban runoff, detecting 6PPD-Q levels of 15.8-39.5 ng L-1 in rivers. In snowmelt, DGT detected 6PPD-Q levels of 210 ng L-1 which is two times higher than the value obtained by grab sampling. 6PPD-Q levels were much higher in snowmelt than those in rivers. This indicates that snowfall constitutes an important transport pathway for 6PPD-Q and that DGT effectively captured the fraction continuously released from dust particles in the snow samples. 6PPD-Q posed a substantial risk to migratory fish in urban waters, and its release from tire wear particles requires further investigation. This study is the first to develop a DGT-based method for 6PPD-Q determination in urban waters, and the method can ensure an accurate measurement of the release of 6PPD-Q to the environment, particularly in rainfall or snowmelt, important pathways for its entry into the aquatic environment.
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Microplastics (MPs) and antibiotics, as two major types of emerging pollutants, inevitably coexist in the soil environment due to agricultural film residue, sewage irrigation and sludge application. However, the impact of MPs on antibiotic availability in soils with varying characteristics has not been extensively studied. Therefore, in this study, an interference experiment was conducted using three types of MPs (polyethylene (PE), polyvinyl chloride (PVC) and polypropylene (PP)) in red soil, paddy soil and cinnamon soil. The available antibiotics in soils were evaluated using diffusive gradients in thin-films (DGT). Results showed that MPs had a significant impact on the amount of antibiotics adsorbed on soil solid (Cs) by providing additional binding sites or altering soil characteristics (e.g., pH and dissolved organic carbon). The most significant effects on Cs were observed in cinnamon soil, and the Cs values were dependent on concentration of MPs. The available antibiotics, as measured by DGT significantly decreased after the addition of MPs. This decrease was influenced by the soil characteristics. However, the concentration of antibiotics in soil solutions (Cd) was only slightly impacted by MPs. Therefore, the influence of MPs on the migration of antibiotics was reflected by their impact on the soil/water partition coefficient (Kd), while the resupply ability (R) from the soil solid phase was less influential. Moreover, the dosage of MPs had a significant effect on the availability of antibiotics in CS by promoting the adsorption of antibiotics on the solid phase, while in RS and PS, the soil properties played a dominate role in the changes in antibiotic availability after MP addition. These results indicate that the impact of MPs on available antibiotics mainly depends on soil properties. In addition, DGT measurement is more sensitive than soil solution to investigate the effects of coexisting pollutants on the behavior of antibiotics in soil.
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Poluentes Ambientais , Poluentes do Solo , Solo/química , Microplásticos , Plásticos , Antibacterianos , Poluentes do Solo/análise , EsgotosRESUMO
AIMS: Norcantharidin (NCTD) exhibits antitumor, anti-inflammatory, and anti-fibrosis properties, which makes NCTD an attractive candidate for the treatment of pathological scars. This study was designed to investigate the potential effects of NCTD on fibroblast proliferation and explore the underlying mechanisms. MATERIALS AND METHODS: First, cell viability and cell apoptosis were evaluated to determine the effects of NCTD on human skin fibroblasts, at 10, 50, and 100 µM. To explore the mechanism, bioinformatics analyses, chromatin immunoprecipitation, RNA immunoprecipitation, and RNA pulldown assays, and luciferase reporter assays were performed to verify the relationships among NCTD, signal transducer and activator of transcription 3 (STAT3), annexin A2 pseudogene 2 (ANXA2P2), and ubiquitin-associated protein 2-like (UBAP2L) mRNA in fibroblasts. Loss-of-function experiments were performed to investigate the roles played by STAT3, ANXA2P2, and UBAP2L in the proliferation and apoptosis of fibroblasts. KEY FINDINGS: We found that NCTD administration induced fibroblast apoptosis and inhibited fibroblast proliferation in a dose-dependent manner. Mechanistically, NCTD inhibited ANXA2P2 transcription through the inhibition of STAT3 phosphorylation. Subsequently, ANXA2P2 was found to enhance the physical interaction between UBAP2L mRNA and lin-28 homolog B (LIN28B), which increased the stability and levels of UBAP2L mRNA. Loss-of-function assays demonstrated that ANXA2P2 and UBAP2L knockdown induced fibroblast apoptosis and suppressed fibroblast proliferation. SIGNIFICANCE: In conclusion, we confirmed that NCTD inhibits fibroblast proliferation by inhibiting the STAT3/ANXA2P2/UBAP2L axis, which suggested that NCTD could represent a new candidate for the treatment of pathological scars.
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Anexina A2/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Proteínas de Transporte/metabolismo , Proliferação de Células , Fibroblastos/citologia , Regulação da Expressão Gênica/efeitos dos fármacos , Estabilidade de RNA/efeitos dos fármacos , Proteínas de Ligação a RNA/metabolismo , Anexina A2/genética , Antineoplásicos/farmacologia , Apoptose , Proteínas de Transporte/genética , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Pseudogenes , Proteínas de Ligação a RNA/genéticaRESUMO
Oxygen-glucose deprivation and reoxygenation (OGD/R)-induced impairment of astrocytes may lead to neuronal dysfunction in the central nervous system (CNS). Apremilast is a phosphodiesterase 4 (PDE4) inhibitor primarily used for the treatment of psoriasis and psoriatic arthritis that has demonstrated certain neuroprotective properties. PDE4 is an isoenzyme that degrades 3'-5'-cyclic adenosine monophosphate (cAMP), which serves as a neuroprotective agent by promoting neuronal recovery through protein kinase (PKA)-mediated phosphorylation of cAMP response element-binding protein (CREB) and subsequent expression of the neurotrophic factor brain-derived neurotrophic factor (BDNF) and anti-apoptotic B cell lymphoma (Bcl-2). However, the effects of apremilast in astrocytes have not been elucidated. In the present study, we employed an in vitro model of ischemic stroke using oxygen-glucose deprivation and reoxygenation (OGD/R)-challenged astrocytes to investigate the effects of apremilast against apoptosis (the flow cytometry assay), cell death (the lactate dehydrogenase release assay), oxidative stress (2', 7' dichlorofluorescin diacetate staining), and the expression of the key neuroprotective factors CREB and BDNF (Western blot analysis). Our findings show that treatment with apremilast could significantly reduce astrocyte apoptosis and cell death induced by OGD/R as evidenced by reduced release of glial fibrillary acidic protein (GFAP) and improvement of the Bax/Bcl-2 ratio. The results of MTT assay, measurement of lactate dehydrogenase (LDH) release, and flow cytometry confirmed the improvement in cell viability mediated by apremilast. Importantly, we found that CREB phosphorylation was required for the increases in BDNF and Bcl-2 induced by apremilast as well as the decrease in astrocyte apoptosis. These preliminary findings indicate that apremilast may have the potential to prevent astrocyte cell death and promote neuronal healing in cerebral ischemic injury. Further in vivo research will expand our understanding of these promising results.
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Apoptose/efeitos dos fármacos , Astrócitos/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Glucose/deficiência , Talidomida/análogos & derivados , Animais , Apoptose/fisiologia , Astrócitos/efeitos dos fármacos , Hipóxia Celular/efeitos dos fármacos , Hipóxia Celular/fisiologia , Relação Dose-Resposta a Droga , Fármacos Neuroprotetores/farmacologia , Inibidores da Fosfodiesterase 4/farmacologia , Ratos , Talidomida/farmacologiaRESUMO
The basic function of the blood-brain barrier (BBB) is to selectively regulate the infiltration of solutes from the circulating blood into the central nervous system (CNS). Impaired BBB activity is related to brain damage caused by stroke, traumatic injury, neurodegenerative diseases, etc. Comprised of a monolayer of endothelial cells, the integrity of the BBB is determined by the expression of tight junction proteins and the contractile activity of the perijunctional apical actomyosin ring. Irbesartan, an AT1R antagonist, has been widely used for the treatment of hypertension. However, the pharmacological function of Irbesartan in the balance of the BBB is still unknown. In the present study, we performed both in-vivo and in-vitro experiments using lipopolysaccharide (LPS) to explore the mechanism behind the protective effects of Irbesartan against the BBB impairment. The results of our mouse model study revealed that Irbesartan could reduce BBB permeability, restore the expression of Occludin, and suppress the expression of inflammatory mediators, including interleukin-6, monocyte chemoattractant protein-1, and intercellular adhesion molecule-1. Additionally, Irbesartan improved LPS-induced depressive-like behavior. In our in vitro experiments, human brain microvascular endothelial cells (HBMVECs) stimulated with LPS demonstrated decreased endothelial permeability and increased occludin expression in response to Irbesartan treatment. Importantly, we found that the protective effects of Irbesartan were mediated through the NF-κB/MLC/MLCK signaling pathway, as blockage of NF-κB abolished the effects of Irbesartan. Our findings provide a basis for further research into the neuroprotective mechanism of Irbesartan.
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Depressão/tratamento farmacológico , Células Endoteliais/fisiologia , Hipertensão/tratamento farmacológico , Inflamação/tratamento farmacológico , Irbesartana/uso terapêutico , Microvasos/patologia , Fármacos Neuroprotetores/uso terapêutico , Actomiosina/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Barreira Hematoencefálica , Permeabilidade Capilar , Linhagem Celular , Células Endoteliais/efeitos dos fármacos , Humanos , Interleucina-6/metabolismo , Irbesartana/farmacologia , Lipopolissacarídeos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Fármacos Neuroprotetores/farmacologia , Ocludina/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Receptores CCR2/metabolismo , Transdução de Sinais , Junções Íntimas/metabolismoRESUMO
Cuticular wax covering the surface of fleshy fruit is closely related to fruit glossiness, development, and post-harvest storage quality. However, the information about formation characteristics and molecular mechanisms of cuticular wax in grape berry is limited. In this study, crystal morphology, chemical composition, and gene expression of cuticular wax in grape berry were comprehensively investigated. Morphological analysis revealed high density of irregular lamellar crystal structures, which were correlated with the glaucous appearances of grape berry. Compositional analysis showed that the dominant wax compounds were triterpenoids, while the most diverse were alkanes. The amounts of triterpenoids declined sharply after véraison, while those of other compounds maintained nearly constant throughout the berry development. The amounts of each wax compounds varied among different cultivars and showed no correlation with berry skin colors. Moreover, the expression profiles of related genes were in accordance with the accumulation of wax compounds. Further investigation revealed the contribution of cuticular wax to the water preservation capacity during storage. These findings not only facilitate a better understanding of the characteristics of cuticular wax, but also shed light on the molecular basis of wax biosynthesis in grape.
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Using biological treatment to deal with harmful algal blooms is highly potential over the physical and chemical methods due to its species specificity and eco-friendly characteristics. In this study, algicidal broth were produced from a Vibrio sp. co-culture composed mainly of V. brasilliensis and V. tubiashii. The productivity of the algicidal compounds was optimized under a dilution rate of 0.1â¯h-1 with a minimum algicidal broth dosage of 0.3% for 100% algal lysis. The algicidal threshold and EC50 of the spray-dried algicidal broth were 0.17 and 0.68â¯g/L, respectively. Treatment with the algicidal agents led to an increase in cellular reactive oxygen species (ROS) level that causes membrane damage as supported by the increase in Malondialdehyde (MDA) levels. and a further inhibition to the antioxidant system as indicated by a sharp decrease in the catalase (CAT) activity. The algicidal compound was identified as hexahydro pyrrolo[1,2-a] pyr azine-1,4-dione.
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Dinoflagellida , Vibrio , Técnicas de Cocultura , Proliferação Nociva de Algas , MalondialdeídoRESUMO
Enteromorpha prolifera (EP) biomass collected from a lake in China was employed for biochar production. The EP biochar was magnetically modified by loading γ-Fe2O3 particles on the surface, and Cr(VI) adsorption behavior and mechanism were evaluated. The magnetic biochar had higher surface polarity, specific surface area and exhibited a higher Cr(VI) adsorption capacity of 95.23â¯mg/g biochar compared with pristine EP biochar. The pronounced electron spin resonance (ESR) signals showed that the environmental persistent free radicals (EPFRs) preferred to form at lower pyrolysis temperature and lower transition metal concentration. The g factors of BC400, BC800 and BCF400 were 1.8959, 1.7955 and 1.7954, respectively, indicating that the EPFRs mainly used carbon atom as center. In addition, biological toxicity of magnetic EP biochar was tested using the microalga Scenedesmus obliquus. Exposure of S. obliquus cells to magnetic biochar led to the accumulation of reactive oxygen species (ROS) and oxidative stress. The leaching solution toxicity of BCF400 was stronger than BCF800. Thus, the magnetic EP biochar prepared at higher temperature (such as BCF800) provide better Cr (VI) performance with low biologic toxicity. And the EP biomass could be a promising low-cost feedstock for biochar production.
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Poluentes Químicos da Água , Adsorção , Carvão Vegetal , China , Cromo/análise , Cromo/toxicidade , Poluentes Químicos da Água/análiseRESUMO
In the present paper, uniform design U10* (10(8)) was used to optimize the condition of arsenic determination in vegetable samples by hydride generation-atomic fluorescence spectrometry. Mathematical model was established and regression analysis was done, and the optimized solutions to those equations were obtained by making use of the UD3.0 software. Combining the life-span of hollow cathode filament, noise of negative voltage and other factors, the optimal condition was obtained as follows: negative voltage was 280-360 V; lamp current was 50-70 mA; carrier gas flow rate was 500-700 mL x min(-1); KBH4 concentration was 15.0-20.0 g x L(-1); HCL concentration was 0.6-1.2 mol x L(-1); sample size was 0.5-1.0 mL. Two samples of vegetable were analyzed under the optimized condition. The results showed that the relative standard deviation was less than 3.6%, and the recovery was within 94.1%-101.3%, with their detection limits of 0.42 microg x L(-1). In this paper, as an effective method of experiment design, uniform design was introduced to hydride generation-atomic fluorescence spectrometry analysis with multifactors, which offered a good idea for the optimization of experiment conditions.
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OBJECTIVE: To investigate the morphological and hemodynamic parameters associated with middle cerebral artery (MCA)bifurcation aneurysm rupture. METHODS: A retrospective study of 67 consecutive patients was carried out based on 3D digital subtraction angiography data. Morphological and hemodynamic parameters including aneurysm size parameters (dome width, height, and perpendicular height), longest dimension from the aneurysm neck to the dome tip, neck width, aneurysm area, aspect ratio, Longest dimension from the aneurysm neck to the dome tip (Dmax) to dome width, and height-width, Bottleneck factor, as well as wall shear stress (WSS), low WSS area (LSA), percentage of LSA (LSA%) and energy loss (EL) were estimated. Parameters between ruptured and un-ruptured groups were analyzed. Receiver operating characteristics were generated to check prediction performance of all significant variables. RESULTS: Sixty-seven patients with MCA bifurcation aneurysm were included (31 unruptured, 36 ruptured). Dmax (p=0.008) was greater in ruptured group than that in un-ruptured group. D/W (p<0.001) and the percentage of the low WSS area (0.09±0.13 vs. 0.01±0.03, p<0.001) were also greater in the ruptured group. Moreover, the EL in ruptured group was higher than that in un-ruptured group (6.39±5.04 vs. 1.53±0.86, p<0.001). Multivariate regression analysis suggested D/W and EL were significant predictors of rupture of MCA bifurcation aneurysms. Correlation analyses revealed the D/W value was positively associated with the EL (R=0.442, p<0.01). CONCLUSION: D/W and EL might be the most two favorable factors to predict rupture risk of MCA bifurcation aneurysms.