A large Stokes shift NIR fluorescent probe for visual monitoring of mitochondrial peroxynitrite during inflammation and ferroptosis and in an Alzheimer's disease model.

The excessive formation of peroxynitrite (ONOO-) in mitochondria has been implicated in various pathophysiological processes and diseases. However, owing to short emission wavelengths and small Stokes shifts, previously reported fluorescent probes pose significant challenges for mitochondrial ONOO- imaging in biological systems. In this study, a near-infrared (NIR) fluorescent probe, denoted as DCO-POT, is designed for the visual monitoring of mitochondrial ONOO-, displaying a remarkable Stokes shift of 170 nm. The NIR fluorophore of DCO-CHO is released by DCO-POT upon the addition of ONOO-, resulting in off-on NIR fluorescence at 670 nm. This phenomenon facilitates the high-resolution confocal laser scanning imaging of ONOO- generated in biological systems. The practical applications of DCO-POT as an efficient fluorescence imaging tool are verified in this study. DCO-POT enables the fluorometric visualization of ONOO- in organelles, cells, and organisms. In particular, ONOO- generation is analyzed during cellular and organism-level (zebrafish) inflammation during ferroptosis and in an Alzheimer's disease mouse model. The excellent visual monitoring performance of DCO-POT in vivo makes it a promising tool for exploring the pathophysiological effects of ONOO-.

Nonphthalate Plasticizers in House Dust from Multiple Countries: An Increasing Threat to Humans.

Along with the restrictions of phthalate esters (PAEs), a variety of nonphthalate plasticizers (NPPs) have been increasingly used for industrial needs. Knowledge remains limited on the environmental occurrences, fate, and human exposure risks of many emerging NPPs. In this study, we investigated a suite of 45 NPPs along with the major PAEs in house dust from five regions in the Asia-Pacific region and the United States. The findings clearly demonstrated ubiquitous occurrences of many NPPs in the home environment, particularly acetyl tributyl citrate (ATBC), tricapryl trimellitate (TCTM), trioctyl trimellitate (TOTM), glycerol monooleate (GMO), methyl oleate (MO), and diisobutyl adipate (DiBA). The median total concentrations of NPPs ranged from 17.8 to 252 µg/g in the study regions, while the mean ratios of ΣNPPs to ΣPAEs ranged from 0.19 (Hanoi) to 0.72 (Adelaide). Spatial differences were observed not only for the chemical abundances but also for the composition profiles and the hazard quotient (HQ) prioritization of individual chemicals. Although the current exposure may unlikely cause significant health risks according to the HQ estimation, potential exposure risks cannot be overlooked, due to the lack of appropriate toxic threshold data, the existence of additional exposure pathways, and possible cocktail effects from coexisting NPPs and PAEs.

Sorption of representative organic contaminants on microplastics: Effects of chemical physicochemical properties, particle size, and biofilm presence.

Microplastic pollution has attracted mounting concerns worldwide. Microplastics may concentrate organic and metallic contaminants; thus, affecting their transport, fate and organismal exposure. To better understand organic contaminant-microplastic interactions, our study explored the sorption of selected polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), α-hexabromocyclododecane (α-HBCDD), and organophosphate flame retardants (OPFRs) on high-density polyethylene (HDPE) and polyvinylchloride (PVC) microplastics under saline conditions. Sorption isotherms determined varied between chemicals and between HDPE and PVC microplastics. Log Freundlich sorption coefficients (Log KF) for the targeted chemicals ranged from 2.01 to 5.27 L kg-1 for HDPE, but were significantly lower for PVC, i.e., ranging from Log KF data (2.84 - 8.58 L kg-1). Significant correlations between chemicals' Log KF and Log Kow (octanol-water partition coefficient) indicate that chemical-dependent sorption was largely influenced by their hydrophobicity. Sorption was evaluated using three size classes (< 53, 53 - 300, and 300 - 1000 µm) of lab-fragmented microplastics. Particle size did not significantly affect sorption isotherms, but influenced the time to reach equilibrium and the predicted maximum sorption, likely related to microplastic surface areas. The presence of biofilms on HDPE particles significantly enhanced contaminant sorption capacity, indicating more complex sorption dynamics in the chemical-biofilm-microplastic system. Our findings offer new insights into the chemical-microplastic interactions in marine environment.

Emerging Plasticizers in South China House Dust and Hand Wipes: Calling for Potential Concern?

Following regulations on legacy plasticizers, a large variety of industrial chemicals have been employed as substitutes to manufacture consumer products. However, knowledge remains limited on their environmental distributions, fate, and human exposure risks. In the present work, we screened for a total of 34 emerging plasticizers in house dust from South China and matched hand wipes collected from volunteers (n = 49 pairs). The results revealed a frequent detection of 27 emerging plasticizers in house dust, with the total concentrations reaching a median level of 106 700 ng/g. Thirteen of them had never been investigated by any environmental studies prior to our work, which included glycerol monooleate (median: 61 600 ng/g), methyl oleate (16 400 ng/g), butyl oleate (411 ng/g), 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate (341 ng/g), 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (105 ng/g), isopropyl myristate (154 ng/g), di(2-ethylhexyl) sebacate (69.1 ng/g), triisononyl trimellitate (64.4 ng/g), as well as a few others. Emerging plasticizers were also frequently detected in hand wipes, with a median total level of 4680 ng, indicating potential exposure via hand-to-mouth contact. Several chemicals, including acetyl tributyl citrate, tributyl citrate, di-n-butyl maleate, isopropyl myristate, and isopropyl palmitate, exhibited significant correlations between dust and hand wipe. However, other plasticizers did not follow this pattern, and the chemical compositional profiles differed between dust and hand wipe, suggesting chemical-specific sources and exposure pathways. Although the estimation of daily intake (EDI) indicated no substantial risks through dust ingestion or hand-to-mouth transfer of emerging plasticizers, continuous monitoring is needed to explore whether some of the important plasticizers are safe replacements or regrettable substitutions of the legacy ones.

"Novel" Synthetic Antioxidants in House Dust from Multiple Locations in the Asia-Pacific Region and the United States.

Synthetic antioxidants represent a complex group of additive chemicals broadly used in consumer products. While traditional antioxidants such as 2,6-di-tert-butyl-4-methylphenol (BHT) have been well studied, a variety of "novel" antioxidants have emerged with extensive applications but received much less attention. Our study aimed to explore a suite of 34 emerging antioxidants in house dust from four different regions, including Guangzhou (China), Adelaide (Australia), Carbondale (Illinois), and Hanoi (Vietnam). The results revealed broad occurrence of several rarely investigated chemicals in house dust across regions, including triethylene glycol bis(3-tert-butyl-4-hydroxy-5-methylphenyl)propionate (AO245), 2,6-di-tert-butyl-4-(dimethylamino)methylphenol (AO4703), 2,2'-thiene-2,5-diylbis(5-tert-butyl-1,3-benzoxazole) (BBOT), 1,3-diphenylguanidine (DPG), 2,4-bis(1,1-dimethylethyl)phenol (2,4DtBP), and 2,6-bis(1,1-dimethylethyl)phenol (2,6DtBP). In particular, DPG exhibited a median concentration of 5030-11 400 ng/g in house dust from the studied regions except for Hanoi (305 ng/g), generally 1 order of magnitude greater than that of BHT (890-1060 ng/g) and dominating the compositional profiles of antioxidants. Estimated intake of target antioxidants by toddlers via dust ingestion, even under the high exposure scenario, was determined to be 2-4 orders of magnitude lower than the reference doses of selected antioxidants. However, potential risks from long-term exposure to a cocktail of antioxidants under environmentally relevant concentrations merit further investigations due to insufficient knowledge on the sources, fate, and toxicokinetics of these chemicals to date.

Transplacental Transfer of Environmental Chemicals: Roles of Molecular Descriptors and Placental Transporters.

Transplacental transfer of environmental chemicals results in direct risks to fetal development. Although numerous studies have investigated transplacental transfer efficiencies (TTEs) of environmental chemicals, the underlying mechanisms and influencing factors remain poorly understood. The present study aims to synthesize a current state of knowledge on the TTEs of major environmental chemicals and explore the roles of chemicals' molecular descriptors and placental transporters in the transplacental transfer. The results indicate great variations in TTEs (median: 0.29-2.86) across 51 chemicals. Chemical-dependent TTEs may partially be attributed to the influences of chemicals' molecular descriptors. Predictive models based on experimental TTEs and 1790 computed molecular descriptors indicate that a very limited number of molecular descriptors, such as the topological polar surface area, may substantially influence and efficiently predict chemicals' TTEs. In addition, molecular docking analyses were conducted to determine the binding affinities between 51 chemicals and six selected transporters, including BCRP, MDR1, hENT1, FRα, SERT, and MRP1. The results reveal transporter- and chemical-dependent binding affinities. Therefore, our study demonstrates that molecular descriptors and placental transporters, among a variety of other factors, can play important roles in the transplacental transfer of environmental chemicals. However, the underlying mechanisms and several important knowledge gaps identified herein require further investigations.

Emerging and legacy per- and polyfluoroalkyl substances in house dust from South China: Contamination status and human exposure assessment.

Our study investigated a large variety of per- and polyfluoroalkyl substances (PFASs) in house dust collected from Guangzhou, South China during 2015-2018. The perfluorobutane sulfonic acid (PFBS) exhibited the highest median concentration (17.6 ng/g), followed by linear perfluorooctanoic acid (L-PFOA; 4.8 ng/g), linear perfluorooctane sulfonic acid (L-PFOS; 4.2 ng/g), 6:2 fluorotelomer phosphate diester (6:2 diPAP; 3.4 ng/g), perfluorodecanoic acid (PFDA; 1.2 ng/g) and perfluoroundecanoic acid (PFUdA; 1.2 ng/g), and 6:2 chlorinated perfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA; 1.1 ng/g). Total concentrations of PFASs (median: 53 ng/g) were generally within the 25-50 percentile of the concentration range reported in global studies. However, our samples exhibited composition profiles different from those reported in many other regions. Analysis based on this and previous studies revealed that the compositions in house dust from East Asia, North America, and Europe exhibit a region-specific pattern. This may indicate region-specific market demands, application patterns, as well as associated human exposure risks. Exploration of dwelling characterizations suggested that renovation history appeared to be a significant factor influencing PFAS concentrations in house dust, although other factors may exist and play a role. Estimation of daily intakes via dust ingestion and dermal contact indicates low exposure risks from these two pathways. However, the PFAS chemical-specific biological effects, possible mixture effects, as well as additional exposure pathways, imply that the risk from indoor PFAS exposure should not be overlooked.

Co-Existence of Organophosphate Di- and Tri-Esters in House Dust from South China and Midwestern United States: Implications for Human Exposure.

Despite numerous studies on the contamination of organophosphate triesters (tri-OPEs) in indoor environments, organophosphate diesters (di-OPEs) have rarely been investigated. The present study aimed to investigate whether di-OPEs coexist with tri-OPEs in house dust collected from Guangzhou ( n = 30), South China and the city of Carbondale ( n = 17) located in the Midwestern United States (U.S.). Median concentrations of bis(2-butoxyethyl) phosphate (BBOEP), bis(1-chloro-2-propyl) phosphate (BCIPP), bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), bis(2-ethylhexyl) phosphate (BEHP), bis(2-methylphenyl phosphate) (BMPP), and diphenyl phosphate (DPHP) were determined to be 15.9, < LOQ, 33.6, 654, 9.5, and 605 ng/g in South China house dust, and 1580, 90.6, 234, 867, 4.0, and 6500 ng/g in Midwestern U.S. dust, respectively. The total concentrations of di-OPEs (referred to ΣdiOPEs) constituted an average of 22.9% and 21.3% of the total concentrations of tri-OPEs in dust from these two locations, respectively. Median concentration ratios of DPHP and BEHP to their respective tri-OPEs (i.e., TPHP and TEHP) were determined to be 1.1 and 1.0 in South China dust and 3.7 and 1.4 in Midwestern U.S. dust, respectively, indicating possible commercial applications for these two di-OPEs. Correlative analyses reveal chemical- and region-specific relationships between di-OPEs and their respective tri-OPEs, suggesting that the relative importance of different sources (e.g., direct commercial use, impurity in tri-OPE formulas, and tri-OPE degradation) could vary for different di-OPEs. Our findings demonstrate wide occurrences of di-OPEs in an indoor environment from the studied locations and raise concerns on human exposure to dust associated di-OPEs. Future studies are needed to explore more possible di-OPEs in indoor environments and elucidate their sources, human exposure pathways, and toxicokinetics.

Beyond Phthalate Diesters: Existence of Phthalate Monoesters in South China House Dust and Implications for Human Exposure.

Despite phthalate monoesters (mono-PAEs) being commonly recognized as metabolic products of phthalate diesters (di-PAEs), investigations on their environmental occurrences, particularly in indoor environments, remain limited. The present study demonstrated the presence mono-PAEs, along with a variety of di-PAEs, in house dust collected from 83 South China families. Among 15 target mono-PAEs, monobutyl phthalate (median concentration, 21.54 µg/g) dominated over other mono-PAEs in indoor dust, followed by monoethylhexyl phthalate (9.44 µg/g), monoisobutyl phthalate (5.14 µg/g), monomethyl phthalate (MMP; 2.05 µg/g), and several others. The total concentrations of detectable mono-PAEs (median, 45.40 µg/g) constituted an average of 6.7 ± 3.7% of the total concentrations of their parent diesters in the same dust. Molar concentration ratios of mono-PAEs to their respective di-PAEs varied greatly among chemicals (median, 0.001-3.1), with the highest ratios determined for the MMP/dimethyl phthalate and mono-/diisopropyl phthalate pairs (i.e., 3.1 and 1.5, respectively). In addition, no significant associations were observed between dust-associated mono- or di-PAEs and urinary mono-PAEs detected in both children (n = 48) and adult participants (n = 41). We hypothesized that mono-PAEs in dust could originate from different sources (e.g., impurities in di-PAE formulas, degradation from di-PAEs, and direct application as commercial additives), while the relative importance of various origins could differ between chemicals. Our findings demonstrate broad occurrences of mono-PAEs in indoor environments, but future studies are needed to better elucidate their sources, fate in indoor and outdoor environments, and potential human health risks.

DEHP and DINP Induce Tissue- and Gender-Specific Disturbances in Fatty Acid and Lipidomic Profiles in Neonatal Mice: A Comparative Study.

Di-isononyl phthalate (DINP) is considered one of the main industrial alternatives to di(2-ethylhexyl)phthalate (DEHP), a well-known chemical with various toxic effects including the disruption with lipid metabolism. However, the potential effects of DINP on lipid metabolism have rarely been investigated in mammals. Our study demonstrated that exposure of neonatal mice to DEHP and DINP at a daily dose of 0.048 or 4.8 mg/kg from postnatal day 0 (PND0) to PND21 caused nonmonotonic as well as tissue- and gender-specific alterations of total fatty acid (FA) compositions in plasma, heart, and adipose tissues. However, the patterns of disruption differed between DEHP- and DINP-treated groups. On the basis of targeted lipidomic analyses, we further identified gender-specific alterations of eight lipid classes in plasma following DEHP or DINP exposure. At the higher dose, DEHP induced decreases in total phosphatidylcholines and phosphatidylinositol (PI) in females and increases in phosphatidylethanolamines (PEs) and triglycerides in males. By contrast, DINP at the higher dose caused alterations of PEs, PIs, phosphatidylserines, and cholesterols exclusively in male mice, but no changes were observed in female pups. Although the most significant dysregulation of lipid metabolism was often observed for the higher dose, the lower one could also disrupt lipid profiles and sometimes its effects may even be more significant than those induced by the higher dose. Our study for the first time identified tissue- and gender-specific disruptions of FA compositions and lipidomic profiles in mice neonatally exposed to DINP. These findings question the suitability of DINP as a safe DEHP substitute and lay a solid foundation for further elucidation of its effects on lipid metabolism and underlying mechanisms.