RESUMEN
A key characteristic to be elucidated, to address the harmful health risks of environmental perfluorinated alkyl substances (PFAS), is their binding modes to serum albumin, the most abundant protein in blood. Hexafluoropropylene oxide-dimer acid (GenX or HFPO-DA) is a new industrial replacement for the widespread linear long-chain PFAS. However, the detailed interaction of new-generation short-chain PFAS with albumin is still lacking. Herein, the binding characteristics of bovine serum albumin (BSA) to GenX were explored at the molecular and cellular levels. It was found that this branched short-chain GenX could bind to BSA with affinity lower than that of legacy linear long-chain perfluorooctanoic acid (PFOA). Site marker competitive study and molecular docking simulation revealed that GenX interacted with subdomain IIIA to form BSA-GenX complex. Consistent with its weaker affinity to albumin protein, the cytotoxicity of branched short-chain GenX was less susceptible to BSA binding compared with that of the linear long-chain PFOA. In contrast to the significant effects of strong BSA-PFOA interaction, the weak affinity of BSA-GenX binding did not influence the structure of protein and the cytotoxicity of GenX. The detailed characterization and direct comparisons of serum albumin interaction with new generation short-chain GenX will provide a better understanding for the toxicological properties of this new alternative.
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Fluorocarburos , Albúmina Sérica Bovina , Animales , Humanos , Caprilatos/química , Contaminantes Ambientales/química , Contaminantes Ambientales/toxicidad , Fluorocarburos/química , Simulación del Acoplamiento Molecular , Albúmina Sérica Bovina/químicaRESUMEN
The notorious tumor microenvironment (TME) usually becomes more deteriorative during phototherapeutic progress that hampers the antitumor efficacy. To overcome this issue, we herein report the ameliorative and adaptive nanoparticles (TPASIC-PFH@PLGA NPs) that simultaneously reverse hypoxia TME and switch photoactivities from photothermal-dominated state to photodynamic-dominated state to maximize phototherapeutic effect. TPASIC-PFH@PLGA NPs are designed by incorporating oxygen-rich liquid perfluorohexane (PFH) into the intraparticle microenvironment to regulate the intramolecular motions of AIE photosensitizer TPASIC. TPASIC exhibits a unique aggregation-enhanced reactive oxygen species (ROS) generation feature. PFH incorporation affords TPASIC the initially dispersed state, thus promoting active intramolecular motions and photothermal conversion efficiency. While PFH volatilization leads to nanoparticle collapse and the formation of tight TPASIC aggregates with largely enhanced ROS generation efficiency. As a consequence, PFH incorporation not only currently promotes both photothermal and photodynamic efficacies of TPASIC and increases the intratumoral oxygen level, but also enables the smart photothermal-to-photodynamic switch to maximize the phototherapeutic performance. The integration of PFH and AIE photosensitizer eventually delivers more excellent antitumor effect over conventional phototherapeutic agents with fixed photothermal and photodynamic efficacies. This study proposes a new nanoengineering strategy to ameliorate TME and adapt the treatment modality to fit the changed TME for advanced antitumor applications.
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Fluorocarburos , Nanopartículas , Fotoquimioterapia , Fármacos Fotosensibilizantes , Especies Reactivas de Oxígeno , Microambiente Tumoral , Nanopartículas/química , Microambiente Tumoral/efectos de los fármacos , Animales , Fotoquimioterapia/métodos , Especies Reactivas de Oxígeno/metabolismo , Fluorocarburos/química , Fluorocarburos/farmacología , Línea Celular Tumoral , Fármacos Fotosensibilizantes/uso terapéutico , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Humanos , Ratones , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Ratones Endogámicos BALB C , Terapia Fototérmica/métodos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Fototerapia/métodos , FemeninoRESUMEN
Perfluoroalkyl substances (PFASs) are typical persistent organic pollutants, and their removal is urgently required but challenging. Photocatalysis has shown potential in PFASs degradation due to the redox capabilities of photoinduced charge carriers in photocatalysts. Herein, hexagonal ZnIn2S4 (ZIS) nanosheets were synthesized by a one-pot oil bath method and were well characterized by a series of techniques. In the degradation of sodium p-perfluorous nonenoxybenzenesulfonate (OBS), one kind of representative PFASs, the as-synthesized ZIS showed activity superior to P25 TiO2 under both simulated sunlight and visible-light irradiation. The good photocatalytic performance was attributed to the enhanced light absorption and facilitated charge separation. The pH conditions were found crucial in the photocatalytic process by influencing the OBS adsorption on the ZIS surface. Photogenerated e- and h+ were the main active species involved in OBS degradation in the ZIS system. This work confirmed the feasibility and could provide mechanistic insights into the degradation and defluorination of PFASs by visible-light photocatalysis.
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Fluorocarburos , Luz , Fotólisis , Fluorocarburos/química , Nanoestructuras/química , Catálisis , Contaminantes Químicos del Agua/química , Zinc/química , Indio/química , Modelos QuímicosRESUMEN
Although there is an association between income status and concentration of perfluoroalkyl and polyfluoroalkyl substance (PFAS), the association remains uncertain in patients with hypertension, hyperlipidemia, and comorbidities. Data from the 2013-2016 National Health and Nutrition Examination Survey were analyzed. A total of 2665 adults were included, and the data included participants' serum PFAS (perfluorooctanoic acid [PFOA], perfluorononaic acid, perfluorodecanoic acid, perfluoroundecanoic acid, perfluorohexane sulfonic acid, and perfluorooctane sulfonic acid) levels and selected covariates. Multivariate linear regression models were used to examine the association between the ratio of family income to poverty (PIR) and individual serum PFAS concentrations in the hypertensive and/or hyperlipidemia groups after adjusting for covariates. The potential effects of sex and age on the results were explored using stratified analysis. A mediating effect model was used to explore the mediating effects of body mass index (BMI) and waist circumference on the association results. After adjusting for potential confounders, for hyperlipidemia and comorbidities (hypertension and hyperlipidemia), serum levels of multiple common PFAS increased by 0.09% (95%Confidence interval [CI] 0.02-0.15%) to 0.13% (95%CI 0.08-0.19%) and 0.10% (95%CI 0.02-0.17%) to 0.12% (95%CI 0.06-0.18%), respectively, with each 1% increase in PIR. The covariate model and stratified analyses results suggested the potential effects of different covariates such as age and sex, leading to changes in the statistical significance of the association results. BMI significantly mediated the effect of PIR on PFOA in hyperlipidemia (13%, P < 0.001). Household income in adults with hyperlipidemia and comorbidities positively correlated with serum PFAS concentration in the United States. Obesity played an indispensable mediating role in the association between economic income and PFAS concentration.
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Fluorocarburos , Hiperlipidemias , Hipertensión , Humanos , Femenino , Masculino , Fluorocarburos/sangre , Hipertensión/sangre , Hipertensión/epidemiología , Persona de Mediana Edad , Adulto , Hiperlipidemias/sangre , Hiperlipidemias/epidemiología , Estados Unidos/epidemiología , Encuestas Nutricionales , Anciano , Ácidos Alcanesulfónicos/sangre , Índice de Masa Corporal , Caprilatos/sangreRESUMEN
Per- and poly-fluoroalkyl substances (PFAS) are emerging contaminants of concern because of their wide use, persistence, and potential to be hazardous to both humans and the environment. Several PFAS have been designated as substances of concern; however, most PFAS in commerce lack toxicology and exposure data to evaluate their potential hazards and risks. Cardiotoxicity has been identified as a likely human health concern, and cell-based assays are the most sensible approach for screening and prioritization of PFAS. Human-induced pluripotent stem cell (iPSC)-derived cardiomyocytes are a widely used method to test for cardiotoxicity, and recent studies showed that many PFAS affect these cells. Because iPSC-derived cardiomyocytes are available from different donors, they also can be used to quantify human variability in responses to PFAS. The primary objective of this study was to characterize potential human cardiotoxic hazard, risk, and inter-individual variability in responses to PFAS. A total of 56 PFAS from different subclasses were tested in concentration-response using human iPSC-derived cardiomyocytes from 16 donors without known heart disease. Kinetic calcium flux and high-content imaging were used to evaluate biologically-relevant phenotypes such as beat frequency, repolarization, and cytotoxicity. Of the tested PFAS, 46 showed concentration-response effects in at least one phenotype and donor; however, a wide range of sensitivities were observed across donors. Inter-individual variability in the effects could be quantified for 19 PFAS, and risk characterization could be performed for 20 PFAS based on available exposure information. For most tested PFAS, toxicodynamic variability was within a factor of 10 and the margins of exposure were above 100. This study identified PFAS that may pose cardiotoxicity risk and have high inter-individual variability. It also demonstrated the feasibility of using a population-based human in vitro method to quantify population variability and identify cardiotoxicity risks of emerging contaminants.
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Cardiotoxicidad , Fluorocarburos , Células Madre Pluripotentes Inducidas , Miocitos Cardíacos , Humanos , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Cardiotoxicidad/etiología , Fluorocarburos/toxicidad , Contaminantes Ambientales/toxicidad , Medición de Riesgo , Adulto , Femenino , Masculino , Exposición a Riesgos Ambientales/efectos adversosRESUMEN
Objective: To explore the feasibility of using cRGD-GNR-PFP-NPs to assess plaque vulnerability in an atherosclerotic plaque mouse model by dual-modal photoacoustic/ultrasonic imaging. Methods: A nanomolecular probe containing gold nanorods (GNRs) and perfluoropentane (PFP) coated with the cyclic Arg-Gly-Asp (cRGD) peptide were prepared by double emulsion solvent evaporation and carbodiimide methods. The morphology, particle size, potential, cRGD conjugation and absorption features of the nanomolecular probe were characterized, along with its in vitro phase transformation and photoacoustic/ultrasonic dual-modal imaging properties. In vivo fluorescence imaging was used to determine the distribution of cRGD-GNR-PFP-NPs in vivo in apolipoprotein E-deficient (ApoE-/-) atherosclerotic plaque model mice, the optimal imaging time was determined, and photoacoustic/ultrasonic dual-modal molecular imaging of integrin αvß3 expressed in atherosclerotic plaques was performed. Pathological assessments verified the imaging results in terms of integrin αvß3 expression and plaque vulnerability. Results: cRGD-GNR-PFP-NPs were spherical with an appropriate particle size (average of approximately 258.03±6.75 nm), a uniform dispersion, and a potential of approximately -9.36±0.53 mV. The probe had a characteristic absorption peak at 780~790 nm, and the surface conjugation of the cRGD peptide reached 92.79%. cRGD-GNR-PFP-NPs were very stable in the non-excited state but very easily underwent phase transformation under low-intensity focused ultrasound (LIFU) and had excellent photoacoustic/ultrasonic dual-modal imaging capability. Mice fed a high-fat diet for 20 weeks had obvious hyperlipidemia with larger, more vulnerable plaques. These plaques could be specifically targeted by cRGD-GNR-PFP-NPs as determined by in vivo fluorescence imaging, and the enrichment of nanomolecular probe increased with the increasing of plaque vulnerability; the photoacoustic/ultrasound signals of the plaques in the high-fat group were stronger. The pathological assessments were in good agreement with the cRGD-GNR-PFP-NPs plaque accumulation, integrin αvß3 expression and plaque vulnerability results. Conclusion: A phase variant photoacoustic/ultrasonic dual-modal cRGD nanomolecular probe was successfully prepared and can be used to identify plaque vulnerability safely and effectively.
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Fluorocarburos , Oro , Nanotubos , Péptidos Cíclicos , Técnicas Fotoacústicas , Placa Aterosclerótica , Animales , Placa Aterosclerótica/diagnóstico por imagen , Técnicas Fotoacústicas/métodos , Oro/química , Péptidos Cíclicos/química , Péptidos Cíclicos/farmacocinética , Ratones , Nanotubos/química , Fluorocarburos/química , Integrina alfaVbeta3/metabolismo , Sondas Moleculares/química , Sondas Moleculares/farmacocinética , Ultrasonografía/métodos , Tamaño de la Partícula , Masculino , Ratones Noqueados para ApoE , Modelos Animales de Enfermedad , PentanosRESUMEN
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Asunto(s)
Carcinoma Hepatocelular , Medios de Contraste , Neoplasias Hepáticas , Ultrasonografía , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Carcinoma Hepatocelular/diagnóstico por imagen , Ultrasonografía/métodos , Óxidos , Compuestos Férricos , Hierro , Fluorocarburos , Sensibilidad y Especificidad , Reproducibilidad de los ResultadosRESUMEN
Background: Per- and polyfluoroalkyl substance (PFAS) exposure and cardiovascular disease are controversial. We aimed to assess the association between serum PFAS exposure and cardiovascular health (CVH) in U.S. adults. Methods: We analyzed serum PFAS concentration data of U.S. adults reported in the National Health and Nutrition Examination Survey (NHANES) study (2005-2018). We employed two weighted logistic regression models and a restricted cubic spline (RCS) to examine the association between each PFAS and impaired CVH (defined as moderate and low CVH). Quantile g-computation (Qgcomp) and weighted quantile sum (WQS) analysis were used to estimate the effects of mixed exposures to PFASs on impaired CVH. Results: PFAS were associated with an increased risk of impaired CVH (ORPFNA: 1.40, 95% CI: 1.09, 1.80; ORPFOA: 1.44, 95% CI: 1.10, 1.88; ORPFOS: 1.62, 95% CI: 1.25, 2.11). PFOA and PFOS exhibited nonlinear relationships with impaired CVH. Significant interactions were observed for impaired CVH between race/ethnicity and PFHxS (p = 0.02), marital status and PFOA (p = 0.03), and both marital status and race/ethnicity with PFOS (p = 0.01 and p = 0.02, respectively). Analysis via WQS and Qgcomp revealed that the mixture of PFAS was positively associated with an increased risk of impaired CVH. Conclusion: PFNA, PFOA, and PFOS exposure are associated with an increased risk of impaired CVH in U.S. adults. Race/ethnicity and marital status may influence CVH. Reducing PFAS exposure could alleviate the burden of disease associated with impaired CVH.
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Enfermedades Cardiovasculares , Exposición a Riesgos Ambientales , Fluorocarburos , Encuestas Nutricionales , Humanos , Estudios Transversales , Fluorocarburos/sangre , Masculino , Femenino , Persona de Mediana Edad , Enfermedades Cardiovasculares/epidemiología , Estados Unidos , Adulto , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Contaminantes Ambientales/sangre , Ácidos Alcanesulfónicos/sangre , Anciano , Factores de RiesgoRESUMEN
BACKGROUND: Although recent in vitro experimental results have raised the question of whether maternal exposure to per- and polyfluoroalkyl substances (PFAS) may be a potential environmental risk factor for chromosomal abnormalities, epidemiological studies investigating these associations are lacking. OBJECTIVES: This study examined whether prenatal PFAS exposure is associated with a higher prevalence of chromosomal abnormalities among offspring. METHODS: We used data from the Japan Environment and Children's Study, a nationwide birth cohort study, and employed logistic regression models to examine the associations between maternal plasma PFAS concentrations in the first trimester and the diagnosis of chromosomal abnormalities in all births (artificial abortions, miscarriages, stillbirths, and live births) up to 2 years of age. In addition, we examined associations with mixtures of PFAS using multipollutant models. RESULTS: The final sample consisted of 24,724 births with singleton pregnancies, of which 44 confirmed cases of chromosomal abnormalities were identified (prevalence: 17.8/10,000 births). When examined individually, exposure to perfluorononanoic acid (PFNA) and perfluorooctane sulfonic acid (PFOS) showed positive associations with any chromosomal abnormalities with age-adjusted odds ratios of 1.81 (95% CI: 1.26, 2.61) and 2.08 (95% CI: 1.41, 3.07) per doubling in concentration, respectively. These associations remained significant after Bonferroni correction, although they did not reach the adjusted significance threshold in certain sensitivity analyses. Furthermore, the doubling in all PFAS included as a mixture was associated with chromosomal abnormalities, indicating an age-adjusted odds ratio of 2.25 (95% CI: 1.34, 3.80), with PFOS as the predominant contributor, followed by PFNA, perfluoroundecanoic acid (PFUnA), and perfluorooctanoic acid (PFOA). DISCUSSION: The study findings suggested a potential association between maternal exposure to PFAS, particularly PFOS, and chromosomal abnormalities in offspring. However, the results should be interpreted cautiously, because selection bias arising from the recruitment of women in early pregnancy may explain the associations. https://doi.org/10.1289/EHP13617.
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Ácidos Alcanesulfónicos , Aberraciones Cromosómicas , Fluorocarburos , Exposición Materna , Humanos , Femenino , Japón/epidemiología , Fluorocarburos/sangre , Fluorocarburos/toxicidad , Embarazo , Exposición Materna/estadística & datos numéricos , Exposición Materna/efectos adversos , Aberraciones Cromosómicas/inducido químicamente , Aberraciones Cromosómicas/estadística & datos numéricos , Ácidos Alcanesulfónicos/sangre , Ácidos Alcanesulfónicos/toxicidad , Adulto , Contaminantes Ambientales/toxicidad , Contaminantes Ambientales/sangre , Masculino , Lactante , Recién Nacido , Efectos Tardíos de la Exposición Prenatal/epidemiología , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Estudios de Cohortes , Preescolar , Cohorte de Nacimiento , Caprilatos/toxicidad , Caprilatos/sangreRESUMEN
Exposure to per- and polyfluoroalkyl substances (PFASs) primarily occurs via consumption of contaminated drinking water and food; however, individuals can also be exposed dermally and via inhalation indoors. This study developed an analytical method for measuring volatile PFASs in silicone wristbands and used them to assess personal exposure in a Midwestern community (n = 87). Paired samples of blood and wristbands were analyzed for PFASs using LC-MS/MS and GC-HRMS to monitor both non-volatile and volatile PFASs. The most frequently detected PFASs in wristbands were: 6:2 diPAP, 6:2 FTOH, MeFOSE and EtFOSE. Females had a 4-fold higher exposure to 6:2 diPAP compared to males and age-dependent differences in exposure to 6:2 FTOH, MeFOSE and EtFOSE were observed. Exposure to MeFOSE and EtFOSE differed based on the average time spent in the home. Frequently detected PFASs in blood were: PFOA, PFOS, PFHxS, PFHpS, and N-MeFOSAA. A strong correlation was found between MeFOSE in the wristbands and N-MeFOSAA in serum (rs = 0.90, p-value <0.001), suggesting exposure to this PFAS was primarily via inhalation and dermal exposure. These results demonstrate that wristbands can provide individual level data on exposure to some polyfluoroalkyl precursors present indoors that reflect serum levels of their suspected biotransformation products.
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Siliconas , Humanos , Femenino , Masculino , Fluorocarburos , Monitoreo del Ambiente/métodos , Contaminación del Aire Interior/análisis , Exposición a Riesgos Ambientales , AdultoRESUMEN
Previous studies regarding the associations between perfluoroalkyl and polyfluoroalkyl substances (PFAS) and autism spectrum disorder (ASD) have yielded inconsistent results, with the underlying mechanisms remaining unknown. In this study, we quantified 13 PFAS in cord serum samples from 396 neonates and followed the children at age 4 to assess ASD-related symptoms. Our findings revealed associations between certain PFAS and ASD-related symptoms, with a doubling of perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) concentrations associated with respective increases of 1.79, 1.62, and 1.45 units in language-related symptoms and PFDA exhibiting an association with higher score of sensory stimuli. Nonlinear associations were observed in the associations of 6:2 chlorinated polyfluorinated ether sulfonate (Cl-PFAES) and 8:2 Cl-PFAES with ASD-related symptoms. Employing weighted quantile sum (WQS) regression, we observed significant mixture effects of multiple PFAS on all domains of ASD-related symptoms, with PFNA emerging as the most substantial contributor. Assuming causality, we found that 39-40% of the estimated effect of long-chain PFAS (PFUnDA and PFDoDA) exposure on sensory stimuli was mediated by androstenedione. This study provides novel epidemiological data about prenatal PFAS mixture exposure and ASD-related symptoms.
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Trastorno del Espectro Autista , Fluorocarburos , Efectos Tardíos de la Exposición Prenatal , Humanos , Femenino , Trastorno del Espectro Autista/epidemiología , Embarazo , Preescolar , Masculino , Recién Nacido , Ácidos DecanoicosRESUMEN
Per- and polyfluoroalkyl substances (PFAS) are widespread environmental contaminants with endocrine-disruptive properties. Their impact on puberty in boys is unclear. In this cross-sectional study, we investigated the association between PFAS exposure and pubertal timing in 300 Norwegian boys (9-16 years), enrolled in the Bergen Growth Study 2 during 2016. We measured 19 PFAS in serum samples and used objective pubertal markers, including ultrasound-measured testicular volume (USTV), Tanner staging of pubic hair development, and serum levels of testosterone, luteinizing hormone, and follicle-stimulating hormone. In addition to logistic regression of single pollutants and the sum of PFAS, Bayesian and elastic net regression were used to estimate the contribution of the individual PFAS. Higher levels of the sum of perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexanesulfonic acid (PFHxS) were associated with later pubertal onset according to USTV (age-adjusted odds ratio (AOR): 2.20, 95% confidence interval (CI): 1.29, 3.93) and testosterone level (AOR: 2.35, 95% CI: 1.34, 4.36). Bayesian modeling showed that higher levels of PFNA and PFHxS were associated with later pubertal onset by USTV, while higher levels of PFNA and perfluoroundecanoic acid (PFUnDA) were associated with later pubertal onset by testosterone level. Our findings indicate that certain PFAS were associated with delay in male pubertal onset.
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Pubertad , Humanos , Masculino , Noruega , Adolescente , Niño , Fluorocarburos/sangre , Contaminantes Ambientales/sangre , Estudios Transversales , Exposición a Riesgos Ambientales , Ácidos Alcanesulfónicos/sangreRESUMEN
Perfluorooctanoic acid (PFOA) as emerging pollutants was largely produced and stable in nature environment. Its fate and effect to the wasted sludge digestion process and corresponding microbial mechanism was rarely reported. This study investigated the different dose of PFOA to the wasted sludge digestion process, where the methane yield and microbial mechanism was illustrated. The PFOA added before digestion were 0-10000 µg/L, no significant variation in daily and accumulated methane production between each group. The 9th day methane yield was significantly higher than other days (p < 0.05). The soluble protein was significantly decreased after 76 days digestion (p < 0.001). The total PFOA in sludge (R2 = 0.8817) and liquid (R2 = 0.9083) phase after digestion was exponentially correlated with PFOA dosed. The PFOA in liquid phase was occupied 54.10 ± 18.38% of the total PFOA in all reactors. The dewatering rate was keep decreasing with the increase of PFOA added (R2 = 0.7748, p < 0.001). The mcrA abundance was significantly correlated with the pH value and organic matter concentration in the reactors. Chloroflexi was the predominant phyla, Aminicenantales, Bellilinea and Candidatus_Cloacimonas were predominant genera in all reactors. Candidatus_Methanofastidiosum and Methanolinea were predominant archaea in all reactors. The function prediction by FAPROTAX and Tax4fun implied that various PFOA dosage resulted in significant function variation. The fermentation and anaerobic chemoheterotrophy function were improved with the PFOA dose. Co-occurrence network implied the potent cooperation among the organic matter degradation and methanogenic microbe in the digestion system. PFOA has little impact to the methane generation while affect the microbe function significantly, its remaining in the digested sludge should be concerned to reduce its potential environmental risks.
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Caprilatos , Fluorocarburos , Metano , Aguas del Alcantarillado , Metano/metabolismo , Fluorocarburos/metabolismo , Anaerobiosis , Aguas del Alcantarillado/microbiología , Caprilatos/metabolismo , Reactores BiológicosRESUMEN
Hexafluoropropylene oxide trimer acid (HFPO-TA), an alternative to perfluorooctanoic acid, has been shown to have estrogenic effects. However, its potential to disrupt fish sex differentiation during gonadal development remains unknown. Therefore, this study exposed zebrafish to HFPO-TA from approximately 2 hours post fertilization (hpf) to 60 days post fertilization (dpf) to investigate its effects on sex differentiation. Results indicated that HFPO-TA disrupted steroid hormone homeostasis, delayed gonadal development in both sexes, and resulted in a female-skewed sex ratio in zebrafish. HFPO-TA exposure up-regulated gene expressions of cyp19a1a, esr1, vtg1 and foxl2, while down-regulated those of amh, sox9a and dmrt1. These suggested that HFPO-TA dysregulated the expressions of key genes related to sex differentiation of zebrafish, promoted the production and activation of estrogen, and further induced the feminization. Interestingly, we observed promoter hypomethylation of cyp19a1a and promoter hypermethylation of amh in male zebrafish, which were negatively associated with their gene expressions. These suggested that HFPO-TA dysregulated these key genes through DNA methylation in their promoters. Therefore, the HFPO-TA disrupted the sex differentiation of zebrafish through an epigenetic mechanism involving DNA methylation, ultimately skewing the sex ratio towards females. Overall, this study demonstrated adverse effects of HFPO-TA on fish sex differentiation and provided novel insights into the underlying epigenetic mechanism.
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Metilación de ADN , Epigénesis Genética , Diferenciación Sexual , Contaminantes Químicos del Agua , Pez Cebra , Animales , Pez Cebra/genética , Diferenciación Sexual/efectos de los fármacos , Femenino , Masculino , Metilación de ADN/efectos de los fármacos , Epigénesis Genética/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Razón de Masculinidad , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Fluorocarburos/toxicidadRESUMEN
Background: Triple negative breast cancer (TNBC) is one of the worst prognosis types of breast cancer that urgently needs effective therapy methods. However, cancer is a complicated disease that usually requires multiple treatment modalities. Methods: A tumor microenvironment (TME)-responsive PFC/TRIM37@Fe-TA@HA (abbreviated as PTFTH) nanoplatform was constructed by coating Fe3+ and tannic acid (TA) on the surface of TRIM37-siRNA loaded phase-transition perfluorocarbon (PFC) nanodroplets and further modifying them with hyaluronic acid (HA) to achieve tumor-specific mild photothermal/gene/ferroptosis synergistic therapy (MPTT/GT/ Ferroptosis) in vitro. Once internalized into tumor cells through CD44 receptor-mediated active targeting, the HA shell of PTFTH would be preliminarily disassembled by hyaluronidase (HAase) to expose the Fe-TA metal-phenolic networks (MPNs), which would further degrade in response to an acidic lysosomal environment, leading to HAase/pH dual-responsive release of Fe3+ and PFC/TRIM37. Results: PTFTH showed good biocompatibility in vitro. On the one hand, the released Fe3+ could deplete the overexpressed glutathione (GSH) through redox reactions and produce Fe2+, which in turn converts endogenous H2O2 into highly cytotoxic hydroxyl radicals (â¢OH) for chemodynamic therapy (CDT). On the other hand, the local hyperthermia generated by PTFTH under 808 nm laser irradiation could not only improve CDT efficacy through accelerating the Fe2+-mediated Fenton reaction, but also enhance TRIM37-siRNA delivery for gene therapy (GT). The consumption of GSH and accumulation of â¢OH synergistically augmented intracellular oxidative stress, resulting in substantial tumor cell ferroptosis. Moreover, PTFTH possessed outstanding contrast enhanced ultrasound (CEUS), photoacoustic imaging (PAI) and magnetic resonance imaging (MRI) ability. Conclusion: This PTFTH based multiple-mode therapeutic strategy has successfully achieved a synergistic anticancer effect in vitro and has the potential to be translated into clinical application for tumor therapy in future.
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Ferroptosis , Glutatión , Ácido Hialurónico , Nanopartículas , Terapia Fototérmica , ARN Interferente Pequeño , Taninos , Neoplasias de la Mama Triple Negativas , Microambiente Tumoral , Humanos , Ferroptosis/efectos de los fármacos , Glutatión/metabolismo , Glutatión/química , Microambiente Tumoral/efectos de los fármacos , Línea Celular Tumoral , Taninos/química , Taninos/farmacología , Nanopartículas/química , Ácido Hialurónico/química , Femenino , Neoplasias de la Mama Triple Negativas/terapia , Neoplasias de la Mama Triple Negativas/genética , ARN Interferente Pequeño/química , ARN Interferente Pequeño/farmacología , ARN Interferente Pequeño/genética , Terapia Fototérmica/métodos , Fluorocarburos/química , Fluorocarburos/farmacología , Proteínas de Motivos Tripartitos/genética , Proteínas de Motivos Tripartitos/metabolismo , Terapia Genética/métodos , Terapia Combinada/métodos , Animales , Hierro/química , Hialuronoglucosaminidasa/genética , Hialuronoglucosaminidasa/metabolismoRESUMEN
Per- and Polyfluoroalkyl Substances (PFAS) are a group of persistent organic pollutants that have received considerable attention from public and regulatory groups. Due to regulations of long-chain PFAS, the use of short-chain and ultrashort-chain PFAS is rapidly growing. Thus, there is an urgent need to develop quantitative methods for determining PFAS with different chain lengths in various environmental matrices. This study introduces an innovative liquid chromatography-mass spectrometry (LC-MS) system combining large volume injection (LVI) and online solid phase extraction (SPE). This system incorporates three columns: a reverse-phase (RP) column, a weak anion exchange (WAX) trap column, and a hybrid HILIC/ion-exchange (HILIC/IE) column, controlled by two valves. With valve switching, ultrashort-chain PFAS that are not retained by the RP column are enriched by the trap column, while other PFAS are separated by the RP column. The trapped ultrashort PFAS are then transferred to the HILIC/IE column for further separation. The LVI significantly enhances the method's sensitivity, allowing for rapid and simultaneous determination of ultrashort-, short- and long- chain PFAS in aqueous samples. The matrix effects from various environmental samples were evaluated, and the results indicate that this unique LC-MS method is suitable for analyzing all chain-length PFAS in various matrices, including surface water, sewage effluent, and seawater. Finally, this novel LC-MS method was applied to quantify PFAS in various water samples.
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Fluorocarburos , Espectrometría de Masas , Extracción en Fase Sólida , Contaminantes Químicos del Agua , Fluorocarburos/análisis , Fluorocarburos/química , Contaminantes Químicos del Agua/análisis , Extracción en Fase Sólida/métodos , Cromatografía Liquida/métodos , Espectrometría de Masas/métodos , Límite de Detección , Reproducibilidad de los Resultados , Cromatografía Líquida con Espectrometría de MasasRESUMEN
This study aimed to explore the isomer-specific, sex-specific, and joint associations of PFAS and red blood cell indices. We used data of 1,238 adults from the Isomers of C8 Health Project in China. Associations of PFAS isomers and red blood cell indices were explored using multiple linear regression models, Bayesian Kernel Machine Regression models and subgroup analysis across sex. We found that serum concentration of linear (n-) and branched (Br-) isomers of perfluorooctane sulfonate (PFOS) and perfluorohexanesulfonic acid (PFHxS) were significantly associated with red blood cell indices in single-pollutant models, with stronger associations observed for n-PFHxS than Br-PFHxS, in women than in men. For instance, the estimated percentage change in hemoglobin concentration for n-PFHxS (3.65%; 95% CI: 2.95%, 4.34%) was larger than that for Br-PFHxS (0.96%; 95% CI: 0.52%, 1.40%). The estimated percentage change in red blood cell count for n-PFHxS in women (2.55%; 95% CI: 1.81%, 3.28%) was significantly higher than that in men (0.12%; 95% CI: -1.04%, 1.29%) (Pinter < 0.001). Similarly, sex-specific positive association of PFAS mixture and outcomes was observed. Therefore, the structure, susceptive population, and joint effect of PFAS isomers should be taken into consideration when evaluating the health risk of chemicals.
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Ácidos Alcanesulfónicos , Contaminantes Ambientales , Índices de Eritrocitos , Fluorocarburos , Humanos , Femenino , Masculino , China , Fluorocarburos/sangre , Ácidos Alcanesulfónicos/sangre , Adulto , Persona de Mediana Edad , Contaminantes Ambientales/sangre , Isomerismo , Ácidos Sulfónicos/sangre , Exposición a Riesgos Ambientales/análisis , Factores SexualesRESUMEN
Per- and polyfluoroalkyl (PFAS) substances are a type of chemical compound unique for their multiple carbon-fluorine bonds, imbuing them with strength and environmental permanence. While legacy substances have been phased out due to human health risks, short-chain and alternative PFAS remain omnipresent. However, a detailed explanation for the pathways through which PFAS interact on a cellular and molecular level is still largely unknown, and the human health effects remain mechanistically unexplained. Of particular interest when focusing on this topic are the interactions between these exogenous chemicals and plasma and membrane proteins. Such proteins include serum albumin which can transport PFAS throughout the body, solute carrier proteins (SLC) and ATP binding cassette (ABC) transporters which are able to move PFAS into and out of cells, and proteins and nuclear receptors which interact with PFAS intracellularly. ABC transporters as a family have little available human data despite being responsible for the export of endogenous substances and drugs throughout the body. The multifactorial regulation of these crucial transporters is affected directly and indirectly by PFAS. Changes, which can include alterations to membrane transport activity and differences in protein expression, vary greatly depending on the specific PFAS and protein of interest. Together, the myriad of changes caused by understudied PFAS exposure to a class of understudied proteins crucial to cellular function and drug treatments has not been fully explored regarding human health and presents room for further exploration. This critical work aims to provide a novel framework of existing human data on PFAS and ABC transporters, allowing for future advancement and investigation into human transporter activity, mechanisms of regulation, and interactions with emerging contaminants.
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Transportadoras de Casetes de Unión a ATP , Contaminantes Ambientales , Fluorocarburos , Humanos , Animales , Fluorocarburos/toxicidad , Transportadoras de Casetes de Unión a ATP/metabolismo , Contaminantes Ambientales/toxicidad , Transporte BiológicoRESUMEN
Human hair is increasingly employed as a non-invasive biomonitoring matrix for exposure to organic contaminants (OCs). Decontamination procedures are generally needed to remove external contamination from hair prior to analysis of OCs. Despite various existing decontamination protocols, their impacts on internally incorporated (endogenous) OCs in hair remain poorly understood. This study aims to quantitatively assess the impact of decontamination procedures on endogenous OCs in hair, and investigate optimal decontamination processes and factors influencing the removal of endogenous OCs. In this study, guinea pig was exposed to 6 OCs (triphenyl phosphate (TPHP), tris(1,3-dichloro-2-propyl) phosphate (TDCPP), and tri-n-butyl phosphate (TNBP), bisphenol A (BPA), perfluorooctanoic acid (PFOA), and phenanthrene (PHE)), and 6 decontamination procedures with different solvents (methanol, n-hexane, acetone, ultrapure water, Triton X-100, and sodium dodecyl sulfate) were used to rinse exposed guinea pig hair. All OCs and three metabolites (diphenyl phosphate (DPHP), dibutyl phosphate (DBP), and bis(1,3-dichloro-2-propyl) phosphate (BDCPP)) were detected in the majority of washing solutions. The decontamination procedures apparently resulted in the release of endogenous OCs from hair. The percentages of residual OCs in hair exhibited a linear or exponential decrease with more washing cycles. Furthermore, the residuals of OCs in hair washed with organic and aqueous solvents showed negative correlations with molecular weight, polarizability, and their initial concentrations. Although these findings need to be validated with a broader range of OCs, the results obtained in this study provide compelling evidence that current hair decontamination procedures have significant impacts on the analysis of endogenous OCs in hair. Therefore, it is important to interpret quantitative data on hair OC concentrations with caution and to thoroughly consider each decontamination procedure during analysis.
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Monitoreo Biológico , Descontaminación , Cabello , Descontaminación/métodos , Cabello/química , Cobayas , Animales , Fluorocarburos/metabolismo , Fluorocarburos/análisis , Contaminantes Orgánicos Persistentes/metabolismo , Compuestos de Bencidrilo , Fenoles/análisis , Caprilatos , Organofosfatos/metabolismo , Fenantrenos/metabolismo , Monitoreo del Ambiente/métodosRESUMEN
SHORT: and ultra-short chain perfluoroalkyl substances (S- and US-PFAS) are alternatives for the long-chain PFAS which have been more regulated over time. They are highly mobile in the environment and can easily reach drinking water sources which can become an important human exposure route. Furthermore, there have been growing concerns about the presence of PFAS in Flanders. Because of this, human exposure to S- and US-PFAS through Flemish drinking water was evaluated in this study. For this purpose, the presence of 2 S-PFAS (PFBS and PFBA) and 5 US-PFAS (PFPrS, PFEtS, TFMS, PFPrA and TFA) was investigated in 47 tap water samples, collected from different Flemish provinces, and 16 bottled waters purchased in Flanders. Out of the 7 target PFAS, 4 (PFBA, PFBS, PFPrS and PFEtS) were detected at concentrations above LOQ in tap water. In bottled water, only TFMS was present above its LOQ. PFAS concentrations in all analyzed water samples ranged from <0.7 to 7.3 ng/L for PFBS, <0.03-15.0 ng/L for TFMS and <0.9-12.0 ng/L for PFBA. PFPrS was only detected once above its LOQ, at 0.6 ng/L. No value could be reported for PFPrA due to high procedural blanks resulting in a high LOQ, nor for TFA due to high matrix effect. No significant differences in PFAS concentrations were seen in tap water among different drinking water companies, provinces, nor between the two types of analyzed bottled water (natural mineral water vs spring water). The use of a commercial carbon filter significantly reduced the median concentrations of the studied compounds in tap water. Finally, it was estimated that the presence of S- and US-PFAS in Flemish drinking water does not pose an immediate threat to human health, as concentrations were at least two orders of magnitude below the available guidance values.