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1.
Environ Int ; 190: 108820, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38906088

RESUMO

PFAS are ubiquitous industrial chemicals with known adverse health effects, particularly on the liver. The liver, being a vital metabolic organ, is susceptible to PFAS-induced metabolic dysregulation, leading to conditions such as hepatotoxicity and metabolic disturbances. In this study, we investigated the phenotypic and metabolic responses of PFAS exposure using two hepatocyte models, HepG2 (male cell line) and HepaRG (female cell line), aiming to define phenotypic alterations, and metabolic disturbances at the metabolite and pathway levels. The PFAS mixture composition was selected based on epidemiological data, covering a broad concentration spectrum observed in diverse human populations. Phenotypic profiling by Cell Painting assay disclosed predominant effects of PFAS exposure on mitochondrial structure and function in both cell models as well as effects on F-actin, Golgi apparatus, and plasma membrane-associated measures. We employed comprehensive metabolic characterization using liquid chromatography combined with high-resolution mass spectrometry (LC-HRMS). We observed dose-dependent changes in the metabolic profiles, particularly in lipid, steroid, amino acid and sugar and carbohydrate metabolism in both cells as well as in cell media, with HepaRG cell line showing a stronger metabolic response. In cells, most of the bile acids, acylcarnitines and free fatty acids showed downregulation, while medium-chain fatty acids and carnosine were upregulated, while the cell media showed different response especially in relation to the bile acids in HepaRG cell media. Importantly, we observed also nonmonotonic response for several phenotypic features and metabolites. On the pathway level, PFAS exposure was also associated with pathways indicating oxidative stress and inflammatory responses. Taken together, our findings on PFAS-induced phenotypic and metabolic disruptions in hepatocytes shed light on potential mechanisms contributing to the broader comprehension of PFAS-related health risks.

2.
J Hazard Mater ; 471: 134401, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38678714

RESUMO

Tire wear particles (TWP) stand out as a major contributor to microplastic pollution, yet their environmental impact remains inadequately understood. This study delves into the cocktail effects of TWP leachates, employing molecular, cellular, and organismal assessments on diverse biological models. Extracted in artificial seawater and analyzed for metals and organic compounds, TWP leachates revealed the presence of polyaromatic hydrocarbons and 4-tert-octylphenol. Exposure to TWP leachates (1.5 to 1000 mg peq L-1) inhibited algae growth and induced zebrafish embryotoxicity, pigment alterations, and behavioral changes. Cell painting uncovered pro-apoptotic changes, while mechanism-specific gene-reporter assays highlighted endocrine-disrupting potential, particularly antiandrogenic effects. Although heavy metals like zinc have been suggested as major players in TWP leachate toxicity, this study emphasizes water-leachable organic compounds as the primary causative agents of observed acute toxicity. The findings underscore the need to reduce TWP pollution in aquatic systems and enhance regulations governing highly toxic tire additives.


Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Animais , Poluentes Químicos da Água/toxicidade , Microplásticos/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Modelos Biológicos
3.
Environ Int ; 183: 108412, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38183898

RESUMO

Due to their exceptional properties and cost effectiveness, polyamides or nylons have emerged as widely used materials, revolutionizing diverse industries, including industrial 3D printing or additive manufacturing (AM). Powder-based AM technologies employ tonnes of polyamide microplastics to produce complex components every year. However, the lack of comprehensive toxicity assessment of particulate polyamides and polyamide-associated chemicals, especially in the light of the global microplastics crisis, calls for urgent action. This study investigated the physicochemical properties of polyamide-12 microplastics used in AM, and assessed a number of toxicity endpoints focusing on inflammation, immunometabolism, genotoxicity, aryl hydrocarbon receptor (AhR) activation, endocrine disruption, and cell morphology. Specifically, microplastics examination by means of field emission scanning electron microscopy revealed that work flow reuse of material created a fraction of smaller particles with an average size of 1-5 µm, a size range readily available for uptake by human cells. Moreover, chemical analysis by means of gas chromatography high-resolution mass spectrometry detected several polyamide-associated chemicals including starting material, plasticizer, thermal stabilizer/antioxidant, and migrating slip additive. Even if polyamide particles and chemicals did not induce an acute inflammatory response, repeated and prolonged exposure of human primary macrophages disclosed a steady increase in the levels of proinflammatory chemokine Interleukin-8 (IL-8/CXCL-8). Moreover, targeted metabolomics disclosed that polyamide particles modulated the kynurenine pathway and some of its key metabolites. The p53-responsive luciferase reporter gene assay showed that particles per se were able to activate p53, being indicative of a genotoxic stress. Polyamide-associated chemicals triggered moderate activation of AhR and elicited anti-androgenic activity. Finally, a high-throughput and non-targeted morphological profiling by Cell Painting assay outlined major sites of bioactivity of polyamide-associated chemicals and indicated putative mechanisms of toxicity in the cells. These findings reveal that the increasing use of polyamide microplastics may pose a potential health risk for the exposed individuals, and it merits more attention.


Assuntos
Nylons , Poluentes Químicos da Água , Humanos , Microplásticos/toxicidade , Plásticos/toxicidade , Proteína Supressora de Tumor p53 , Plastificantes , Poluentes Químicos da Água/análise
4.
Cells ; 12(2)2023 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-36672217

RESUMO

Additive manufacturing (AM) or industrial 3D printing uses cutting-edge technologies and materials to produce a variety of complex products. However, the effects of the unintentionally emitted AM (nano)particles (AMPs) on human cells following inhalation, require further investigations. The physicochemical characterization of the AMPs, extracted from the filter of a Laser Powder Bed Fusion (L-PBF) 3D printer of iron-based materials, disclosed their complexity, in terms of size, shape, and chemistry. Cell Painting, a high-content screening (HCS) assay, was used to detect the subtle morphological changes elicited by the AMPs at the single cell resolution. The profiling of the cell morphological phenotypes, disclosed prominent concentration-dependent effects on the cytoskeleton, mitochondria, and the membranous structures of the cell. Furthermore, lipidomics confirmed that the AMPs induced the extensive membrane remodeling in the lung epithelial and macrophage co-culture cell model. To further elucidate the biological mechanisms of action, the targeted metabolomics unveiled several inflammation-related metabolites regulating the cell response to the AMP exposure. Overall, the AMP exposure led to the internalization, oxidative stress, cytoskeleton disruption, mitochondrial activation, membrane remodeling, and metabolic reprogramming of the lung epithelial cells and macrophages. We propose the approach of integrating Cell Painting with metabolomics and lipidomics, as an advanced nanosafety methodology, increasing the ability to capture the cellular and molecular phenotypes and the relevant biological mechanisms to the (nano)particle exposure.


Assuntos
Lipidômica , Metabolômica , Humanos , Pulmão/metabolismo , Células Epiteliais , Fenótipo
5.
Opt Express ; 29(7): 11254-11267, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33820241

RESUMO

We evaluate improvement in the performance of the optical transmission systems operating with the continuous nonlinear Fourier spectrum by the artificial neural network equalisers installed at the receiver end. We propose here a novel equaliser designs based on bidirectional long short-term memory (BLSTM) gated recurrent neural network and compare their performance with the equaliser based on several fully connected layers. The proposed approach accounts for the correlations between different nonlinear spectral components. The application of BLSTM equaliser leads to a 16x improvement in terms of bit-error rate (BER) compared to the non-equalised case. The proposed equaliser makes it possible to reach the data rate of 170 Gbit/s for one polarisation conventional nonlinear Fourier transform (NFT) based system at 1000 km distance. We show that our new BLSTM equalisers significantly outperform the previously proposed scheme based on a feed-forward fully connected neural network. Moreover, we demonstrate that by adding a 1D convolutional layer for the data pre-processing before BLSTM recurrent layers, we can further enhance the performance of the BLSTM equaliser, reaching 23x BER improvement for the 170 Gbit/s system over 1000 km, staying below the 7% forward error correction hard decision threshold (HD-FEC).

6.
Opt Lett ; 45(13): 3462-3465, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32630872

RESUMO

We propose a method to improve the performance of the nonlinear Fourier transform (NFT)-based optical transmission system by applying the neural network post-processing of the nonlinear spectrum at the receiver. We demonstrate through numerical modeling about one order of magnitude bit error rate improvement and compare this method with machine learning processing based on the classification of the received symbols. The proposed approach also offers a way to improve numerical accuracy of the inverse NFT; therefore, it can find a range of applications beyond optical communications.

7.
Chem Commun (Camb) ; 55(32): 4683-4686, 2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30938726

RESUMO

A post-synthesis thermal treatment of metastable phases in the high-pressure stabilised perovskite BiFe1-yScyO3 system results in the irreversible formation of polymorphs which represent novel polar and antipolar structures with interesting magnetic properties. Such annealing-stimulated polymorphism is believed to be a general phenomenon which can be found in other systems.


Assuntos
Bismuto/química , Compostos de Ferro/química , Óxidos/química , Escândio/química , Fenômenos Magnéticos , Transição de Fase , Pressão
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