Search

The total oxidizable precursor (TOP) assay has been extensively used for detecting PFAS pollutants that do not have analytical standards. It uses hydroxyl radicals (HO•) from the heat activation of persulfate under alkaline pH to convert H-containing precursors to perfluoroalkyl carboxylates (PFCAs) for target analysis. However, the current TOP assay oxidation method does not apply to emerging PFAS because (i) many structures do not contain C-H bonds for HO• attack and (ii) the transformation products are not necessarily PFCAs. In this study, we explored the use of classic acidic persulfate digestion, which generates sulfate radicals (SO4-•), to extend the capability of the TOP assay. We examined the oxidation of Nafion-related ether sulfonates that contain C-H or -COO-, characterized the oxidation products, and quantified the F atom balance. The SO4-• oxidation greatly expanded the scope of oxidizable precursors. The transformation was initiated by decarboxylation, followed by various spontaneous steps, such as HF elimination and ester hydrolysis. We further compared the oxidation of legacy fluorotelomers using SO4-• versus HO•. The results suggest novel product distribution patterns, depending on the functional group and oxidant dose. The general trends and strategies were also validated by analyzing a mixture of 100000- or 10000-fold diluted aqueous film-forming foam (containing various fluorotelomer surfactants and organics) and a spiked Nafion precursor. Therefore, (1) the combined use of SO4-• and HO• oxidation, (2) the expanded list of standard chemicals, and (3) further elucidation of SO4-• oxidation mechanisms will provide more critical information to probe emerging PFAS pollutants.

BackgroundNontargeted analysis (NTA) methods identify novel exposures; however, few chemicals have been quantified and interrogated with pregnancy complications.ObjectivesWe characterized levels of nine exogenous and endogenous chemicals in maternal and cord blood identified, selected, and confirmed in prior NTA steps, including linear and branched isomers perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), monoethylhexyl phthalate, 4-nitrophenol, tetraethylene glycol, tridecanedioic acid, octadecanedioic acid, and deoxycholic acid. We evaluated relationships between maternal and cord levels and between gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy in a diverse pregnancy cohort in San Francisco.MethodsWe collected matched maternal and cord serum samples at delivery from 302 pregnant study participants from the Chemicals in Our Bodies cohort in San Francisco. Chemicals were identified via NTA and quantified using targeted approaches. We calculated distributions and Spearman correlation coefficients testing the relationship of chemicals within and between the maternal and cord blood matrices. We used adjusted logistic regression to calculate the odds of GDM and hypertensive disorders of pregnancy associated with an interquartile range increase in maternal chemical exposures.ResultsWe detected linear PFOS, PFHxS, octadecanedioic acid, and deoxycholic acid in at least 97% of maternal samples. Correlations ranged between -0.1 and 0.9. We observed strong correlations between cord and maternal levels of PFHxS, linear PFOS, and branched PFOS (coefficient=0.9, 0.8, and 0.8, respectively). An interquartile range increase in linear and branched PFOS, tridecanedioic acid, octadecanedioic acid, and deoxycholic acid was associated with increased odds ratio (OR) of GDM [OR=1.33 (95% CI: 0.89, 2.01), 1.24 (95% CI: 0.86, 1.80), 1.26 (95% CI: 0.93, 1.73), 1.24 (95% CI: 0.86, 1.80), and 1.23 (95% CI: 0.87, 1.75), respectively]. Tridecanedioic acid was positively associated with hypertensive disorders of pregnancy [OR=1.28 (95% CI: 0.90, 1.86)].DiscussionWe identified both exogenous and endogenous chemicals seldom quantified in pregnant study participants that were also related to pregnancy complications and demonstrated the utility of NTA to identify chemical exposures of concern. https://doi.org/10.1289/EHP11546.

A new series of hydrazone derivatives incorporating spirocyclic aminopyrimidine with aryl alkanesulfonates were synthesized. The targeted products were obtained in excellent yields via an acid catalyzed reaction of spirocyclic hydrazinopyrimidine with aryl aldehyde sulfonates. The structures of the synthesized hydrazones were studied by the different spectroscopic tools, in addition to the high resolution mass analysis. The antiproliferative activities of the compounds were tested in vitro against the National Cancer Institute (NCI) 60 cell panel by the Developmental Therapeutics Program. Amongst the tested hydrazone compounds, the methansulfonate derivatives showed the highest activities against lung, brain, kidney, and breast cancers. [ABSTRACT FROM AUTHOR]

Cation exchange resins are commonly used as treatment for hyperkalaemia in patients with chronic renal disease. There is a relation between cation exchange resins and the development of gastrointestinal adverse effects. A case of an intestinal obstruction at the terminal ileum is presented that underwent an ileocolic resection because of a critical stenosis of the intestine. The pathologist revealed abundant inflammatory cells together with deposits of calcium polystyrene crystals responsible of the intestinal obstruction. A rare cause of intestinal obstruction to bear in mind in chronically medicated patients with cation exchange resins. [ABSTRACT FROM AUTHOR]

The UV-sulfite reductive treatment using hydrated electrons (eaq-) is a promising technology for destroying perfluorocarboxylates (PFCAs, CnF2n+1COO-) in any chain length. However, the C-H bonds formed in the transformation products strengthen the residual C-F bonds and thus prevent complete defluorination. Reductive treatments of fluorotelomer carboxylates (FTCAs, CnF2n+1-CH2CH2-COO-) and sulfonates (FTSAs, CnF2n+1-CH2CH2-SO3-) are also sluggish because the ethylene linker separates the fluoroalkyl chain from the end functional group. In this work, we used oxidation (Ox) with hydroxyl radicals (HO•) to convert FTCAs and FTSAs to a mixture of PFCAs. This process also cleaved 35-95% of C-F bonds depending on the fluoroalkyl chain length. We probed the stoichiometry and mechanism for the oxidative defluorination of fluorotelomers. The subsequent reduction (Red) with UV-sulfite achieved deep defluorination of the PFCA mixture for up to 90%. The following use of HO• to oxidize the H-rich residues led to the cleavage of the remaining C-F bonds. We examined the efficacy of integrated oxidative and reductive treatment of n = 1-8 PFCAs, n = 4,6,8 perfluorosulfonates (PFSAs, CnF2n+1-SO3-), n = 1-8 FTCAs, and n = 4,6,8 FTSAs. A majority of structures yielded near-quantitative overall defluorination (97-103%), except for n = 7,8 fluorotelomers (85-89%), n = 4 PFSA (94%), and n = 4 FTSA (93%). The results show the feasibility of complete defluorination of legacy PFAS pollutants and will advance both remediation technology design and water sample analysis.

BackgroundA highly regulated trafficking of cargo vesicles in eukaryotes performs protein delivery to a variety of cellular compartments of endomembrane system. The two main routes, the secretory and the endocytic pathways have pivotal functions in uni- and multi-cellular organisms. Protein delivery and targeting includes cargo recognition, vesicle formation and fusion. Developing new tools to modulate protein trafficking allows better understanding the endomembrane system mechanisms and their regulation. The compound Sortin2 has been described as a protein trafficking modulator affecting targeting of the vacuolar protein carboxypeptidase Y (CPY), triggering its secretion in Saccharomyces cerevisiae.ResultsA reverse chemical-genetics approach was used to identify key proteins for Sortin2 bioactivity. A genome-wide Sortin2 resistance screen revealed six yeast deletion mutants that do not secrete CPY when grown at Sortin2 condition where the parental strain does: met18, sla1, clc1, dfg10, dpl1 and yjl175w. Integrating mutant phenotype and gene ontology annotation of the corresponding genes and their interactome pointed towards a high representation of genes involved in the endocytic process. In wild type yeast endocytosis towards the vacuole was faster in presence of Sortin2, which further validates the data of the genome-wide screen. This effect of Sortin2 depends on structural features of the molecule, suggesting compound specificity. Sortin2 did not affect endocytic trafficking in Sortin2-resistant mutants, strongly suggesting that the Sortin2 effects on the secretory and endocytic pathways are linked.ConclusionsOverall, the results reveal that Sortin2 enhances the endocytic transport pathway in Saccharomyces cerevisiae. This cellular effect is most likely at the level where secretory and endocytic pathways are merged. Them Sortin2 specificity over the endomembrane system places it as a powerful biological modulator for cell biology.

Pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) are mediators in the development of many inflammatory diseases. To demonstrate that macrophages take up and respond to thermosensitive nanoparticle drug carriers, we synthesized PEGylated poly(N-isopropylacrylamide-2-acrylamido-2-methyl-1-propanesulfonate) particles cross-linked with degradable disulfide (N,N'-bis(acryloyl)cystamine) (NGPEGSS). An anti-inflammatory peptide (KAFAK) was loaded and released from the thermosensitive nanoparticles and shown to suppress levels of TNF-α and IL-6 production in macrophages. Cellular uptake of fluorescent, thermosensitive, and degradable nanoparticles and therapeutic efficacy of free KAFAK peptide compared to that of KAFAK loaded in PEGylated degradable thermosensitive nanoparticles were examined. The data suggests that the degradable, thermosensitive nanoparticles loaded with KAFAK may be an effective tool to treat inflammatory diseases.

Background: No study has examined the association between per- and polyfluoroalkyl substances (PFAS) exposure and chronic obstructive pulmonary disease (COPD) risk. This study aims to explore this relationship., Methods: This study enrolled 4541 individuals who had available data on PFAS, COPD, and covariates from NHANES 2007-2018. Serum PFAS including perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS) were analyzed, because of high detective rates. Considering the skew distribution of PFAS levels, the natural logarithm-transformed PFAS (Ln-PFAS) was used. Logistic regression analysis, restricted cubic spline (RCS), and weighted quantile sum (WQS) regression were performed to explore the single, nonlinear, and mixed effects. A mediating analysis was used to evaluate the mediated effects of albumin., Results: Individuals with COPD had higher levels of PFHxS, PFNA, PFOA, and PFOS compared to those without COPD. Ln-PFNA (OR males : 1.92, 95 % CI:1.31 to 2.80, P: <0.001; OR females : 1.07, 95 % CI: 0.81 to 1.40, P: 0.636) and ln-PFOA (OR males : 2.17, 95 % CI:1.38 to 3.41, P: <0.001; OR females : 1.49, 95 % CI: 1.08 to 2.05, P: 0.016) were associated with COPD risk especially in males. The interaction between PFNA exposure and sex on COPD risk was significant (P interaction : <0.001). The RCS curve demonstrated the nonlinear relationship between the ln-PFOA (P nonlinear :0.001), ln-PFNA (P nonlinear :0.045), and COPD risk in males. WQS analysis showed mixed PFAS exposure was correlated with COPD risk in males (OR: 1.44, 95 % CI:1.18 to 1.75, P: <0.001). Albumin mediated the relationship between PFOA and COPD (mediated proportion: -17.94 %)., Conclusion: This study concludes PFOA and PFNA are linked to a higher COPD risk in males, and serum albumin plays a mediating role in the relationship between PFOA and COPD. Thess findings are beneficial for the prevention of COPD. Further studies are required to explore potential mechanisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Prior studies suggest that prenatal per- and polyfluoroalkyl substances (PFAS) exposures are associated with shorter breastfeeding duration. Studies assessing PFAS mixtures and populations in North America are sparse., Methods: We quantified PFAS concentrations in maternal plasma collected during pregnancy in the New Hampshire Birth Cohort Study (2010-2017). Participants completed standardized breastfeeding surveys at regular intervals until weaning (n = 813). We estimated associations between mixtures of 5 PFAS and risk of stopping exclusive breastfeeding before 6 months or any breastfeeding before 12 months using probit Bayesian kernel machine regression. For individual PFAS, we calculated the relative risk and hazard ratio (HR) of stopping breastfeeding using modified Poisson regression and accelerated failure time models respectively., Results: PFAS mixtures were associated with stopping exclusive breastfeeding before 6 months, primarily driven by perfluorooctanoate (PFOA). We observed statistically significant trends in the association of perfluorohexane sulfonate (PFHxS), PFOA, and perfluorononanoate (PFNA) (p-trends≤0.02) with stopping exclusive breastfeeding. Participants in the highest PFOA quartile had a 28% higher risk of stopping exclusive breastfeeding before 6 months compared to those in the lowest quartile (95% Confidence Interval: 1.04, 1.56). Similar trends were observed for PFHxS and PFNA with exclusive breastfeeding (p-trends≤0.05). PFAS were not associated with stopping any breastfeeding before 12 months., Conclusions: In this cohort, we observed that participants with greater overall plasma PFAS concentrations had greater risk of stopping exclusive breastfeeding before 6 months and associations were driven largely by PFOA. These findings further support the growing literature indicating that PFAS may be associated with shorter duration of breastfeeding., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Per- and polyfluoroalkyl substances (PFAS) are synthetic organofluorine compounds known for their chemical and physical stability as well as their wide range of uses. Some PFAS are widely distributed in the environment, leading to concerns related to both environmental and human health. High temperature thermal treatment (i.e., incineration) has been utilized for PFAS treatment, but this requires significant infrastructure and energy, prompting interest in lower temperature approaches that may still lead to efficient destruction. Lower treatment temperatures, however, increase the potential for incomplete PFAS mineralization and formation of volatile organofluorine (VOF) products. Herein, we report the formation of novel VOF products that include chlorinated and brominated compounds during the thermal treatment of potassium perfluorohexane sulfonate (PFHxS), a representative perfluoroalkyl acid (PFAA). By comparing the gas chromatography-mass spectrometry (GC-MS) results of known VOF stocks to evolved VOF during thermal treatment of PFAS, the formation of perfluorohexyl chloride and perfluorohexyl bromide was observed when PFHxS was heated at temperatures between 275 and 475 °C in the presence of NaCl and NaBr, respectively. To our knowledge, this is the first report of chlorinated or brominated VOF products during thermal treatment of a PFAA. These findings suggest that a range of mixed halogenated VOF may form during thermal treatment of PFAS at relatively low temperature (e.g., 500 °C) and that these can be a function of salts present in the matrix., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The widespread detection of per- and polyfluoroalkyl substances (PFAS) in environmental compartments across the globe has raised several health concerns. Destructive technologies that aim to transform these recalcitrant PFAS into less toxic, more manageable products, are gaining impetus to address this problem. In this study, a 9 MeV electron beam accelerator was utilized to treat a suite of PFAS (perfluoroalkyl carboxylates: PFCAs, perfluoroalkyl sulfonates, and 6:2 fluorotelomer sulfonate: FTS) at environmentally relevant levels in water under different operating and water quality conditions. Although perfluorooctanoic acid and perfluorooctane sulfonic acid showed >90% degradation at <500 kGy dose at optimized conditions, a fluoride mass balance revealed that complete defluorination occurred only at/or near 1000 kGy. Non-target and suspect screening revealed additional degradation pathways differing from previously reported mechanisms. Treatment of PFAS mixtures in deionized water and groundwater matrices showed that FTS was preferentially degraded (∼90%), followed by partial degradation of long-chain PFAS (∼15-60%) and a simultaneous increase of short-chain PFAS (up to 20%) with increasing doses. The increase was much higher (up to 3.5X) in groundwaters compared to deionized water due to the presence of PFAS precursors as confirmed by total oxidizable precursor (TOP) assay. TOP assay of e-beam treated samples did not show any increase in PFCAs, confirming that e-beam was effective in also degrading precursors. This study provides an improved understanding of the mechanism of PFAS degradation and revealed that short-chain PFAS are more resistant to defluorination and their levels and regulation in the environment will determine the operating conditions of e-beam and other PFAS treatment technologies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Eumelanin is a natural pigment that can be particularly valuable for sustainable bioelectronic devices due to its inherent biocompatibility and hydration-dependent conductivity. However, the low conductivity of eumelanin limits its technological development. In this research, electrochemical doping was proposed as an alternative route to increase the electronic conductivity of synthetic eumelanin derivatives. Thin films of sulfonated eumelanin were deposited on platinum interdigitated electrodes and electrochemically treated by using cyclic voltammetry and chronoamperometry treatments. X-ray photoelectron spectroscopy analysis confirmed ion doping in sulfonated melanin. Current-voltage, current-time, and electrochemical impedance measurements were used to investigate the effect of different aqueous electrolytes (including KCl and LiClO 4 ) treatments on the charge transport of sulfonated eumelanin. We show that the conductivity depends on the type and size of the anion used and can reach 10 -3 S·cm -1 . Additionally, depending on the electrolyte, there is a change in charge transport from mixed ionic/electronic to a predominantly electronic-only conduction. Our results show that the chemical nature of the ion plays an important role in the electrochemical doping and, consequently, in the charge transport of eumelanin. These insights serve as inspiration to explore the use of alternative electrolytes with different compositions further and develop eumelanin-based devices with tunable conductivities.

Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) is inevitable among pregnant women. Nevertheless, there is a scarcity of research investigating the connections between prenatal PFAS exposure and the placental structure and efficiency. Based on 712 maternal-fetal dyads in the Ma'anshan Birth Cohort, we analyzed associations between individual and mixed PFAS exposure and placental measures. We repeatedly measured 12 PFAS in the maternal serum during pregnancy. Placental weight, scaling exponent, chorionic disc area, and disc eccentricity were used as the outcome variables. Upon adjusting for confounders and implementing corrections for multiple comparisons, we identified positive associations between branched perfluorohexane sulfonate (br-PFHxS) and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) with placental weight. Additionally, a positive association was observed between br-PFHxS and the scaling exponent, where a higher scaling exponent signified reduced placental efficiency. Based on neonatal sex stratification, female infants were found to be more susceptible to the adverse effects of PFAS exposure. Mixed exposure modeling revealed that mixed PFAS exposure was positively associated with placental weight and scaling exponent, particularly during the second and third trimesters. Furthermore, br-PFHxS and 6:2 Cl-PFESA played major roles in the placental measures. This study provides the first epidemiological evidence of the relationship between prenatal PFAS exposure and placental measures.

Objective: To investigate the relationships between perfluoroalkyl and polyfluoroalkyl substances (PFASs) exposure and glucose metabolism indices., Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 waves were used. A total of 611 participants with information on serum PFASs (perfluorononanoic acid (PFNA); perfluorooctanoic acid (PFOA); perfluoroundecanoic acid (PFUA); perfluorohexane sulfonic acid (PFHxS); perfluorooctane sulfonates acid (PFOS); perfluorodecanoic acid (PFDeA)), glucose metabolism indices (fasting plasma glucose (FPG), homeostasis model assessment for insulin resistance (HOMA-IR) and insulin) as well as selected covariates were included. We used cluster analysis to categorize the participants into three exposure subgroups and compared glucose metabolism index levels between the subgroups. Least absolute shrinkage and selection operator (LASSO), multiple linear regression analysis and Bayesian kernel machine regression (BKMR) were used to assess the effects of single and mixed PFASs exposures and glucose metabolism., Results: The cluster analysis results revealed overlapping exposure types among people with higher PFASs exposure. As the level of PFAS exposure increased, FPG level showed an upward linear trend ( p  < 0.001), whereas insulin levels demonstrated a downward linear trend ( p  = 0.012). LASSO and multiple linear regression analysis showed that PFNA and FPG had a positive relationship (>50 years-old group: β  = 0.059, p  < 0.001). PFOA, PFUA, and PFHxS (≤50 years-old group: insulin β  = -0.194, p  < 0.001, HOMA-IR β  = -0.132, p  = 0.020) showed negative correlation with HOMA-IR/insulin. PFNA (>50 years-old group: insulin β  = 0.191, p  = 0.018, HOMA-IR β  = 0.220, p  = 0.013) showed positive correlation with HOMA-IR/insulin, which was essentially the same as results that obtained for the univariate exposure-response map in the BKMR model. Association of exposure to PFASs on glucose metabolism indices showed positive interactions between PFOS and PFHxS and negative interactions between PFOA and PFNA/PFOS/PFHxS., Conclusion: Our study provides evidence that positive and negative correlations between PFASs and FPG and HOMA-IR/insulin levels are observed, respectively. Combined effects and interactions between PFASs. Given the higher risk of glucose metabolism associated with elevated levels of PFAS, future studies are needed to explore the potential underlying mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tian, Yang, An, Li, Wang, Zhang, Zhang, Zhang, Mu and Lei.)

The perfluoalkyl substance (PFASs) perfluorooctane sulfonate (PFOS) has been widely used in industry. However, PFOS is a persistent organic pollutant and has been gradually replaced by its short-chain analogs, perfluorohexane sulfonate (PFHxS) and perfluorobutane sulfonate (PFBS). PFASs are extremely persistent and are very frequently detected among the general population. The aim of the study was to determine the effect of selected PFASs on peripheral blood mononuclear cells (PBMCs) and the mechanisms of their action. PBMCs were exposed to PFOS, PFBS and PFHxS at concentrations ranging from 0.02 to 400 μM for 24 h, they were then tested for viability, apoptosis (changes in cytosolic calcium ions level and caspase-3, -8 and -9 activation), ferroptosis (changes in chelatable iron ions level and lipid peroxidation), and autophagy (LC3-II and Raptor level assay). PFOS exposure decreased cell viability, increased calcium ion level and caspase-8 activation; it also enhanced lipid peroxidation and increased the intracellular pool of chelatable iron ions as well as LC3-II protein content. In contrast, short-chain PFBS and PFHxS induced significant changes in the markers of apoptosis but had no substantial impact on ferroptosis or autophagy markers over a wide range of concentrations. Our results indicate that only PFOS demonstrated pro-ferroptotic and pro-autophagic potential but observed changes occurred at relatively high exposure. A short-chain substitute (PFBS) exhibited strong pro-apoptotic potential at concentrations related to occupational exposure. While the short-chain PFASs strongly affected the mitochondrial pathway of apoptosis, apoptosis itself was only induced by PFBS via the intrinsic and extrinsic pathways. It seems that the length of the carbon chain in PFASs appears to determine the cell death mechanisms activated in human PBMCs following exposure. Our findings provide a new insight into the immune toxicity mechanism induced by these compounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)