@article {285, title = {Ligand interaction landscape of transcription factors and essential enzymes in E.~coli.}, journal = {Cell}, year = {2025}, month = {2025 Jan 22}, abstract = {

Knowledge of protein-metabolite interactions can enhance mechanistic understanding and chemical probing of biochemical processes, but the discovery of endogenous ligands remains challenging. Here, we combined rapid affinity purification with precision mass spectrometry and high-resolution molecular docking to precisely map the physical associations of 296 chemically diverse small-molecule metabolite ligands with 69 distinct essential enzymes and 45 transcription factors in the gram-negative bacterium Escherichia coli. We then conducted systematic metabolic pathway integration, pan-microbial evolutionary projections, and independent in-depth biophysical characterization experiments to define the functional significance of ligand interfaces. This effort revealed principles governing functional crosstalk on a network level, divergent patterns of binding pocket conservation, and scaffolds for designing selective chemical probes. This structurally resolved ligand interactome mapping pipeline can be scaled to illuminate the native small-molecule networks of complete cells and potentially entire multi-cellular communities.

}, issn = {1097-4172}, doi = {10.1016/j.cell.2025.01.003}, author = {Peng, Hui and Kotelnikov, Sergei and Egbert, Megan E and Ofaim, Shany and Stevens, Grant C and Phanse, Sadhna and Saccon, Tatiana and Ignatov, Mikhail and Dutta, Shubham and Istace, Zoe and Moutaoufik, Mohamed Taha and Aoki, Hiroyuki and Kewalramani, Neal and Sun, Jianxian and Gong, Yufeng and Padhorny, Dzmitry and Poda, Gennady and Alekseenko, Andrey and Porter, Kathryn A and Jones, George and Rodionova, Irina and Guo, Hongbo and Pogoutse, Oxana and Datta, Suprama and Saier, Milton and Crovella, Mark and Vajda, Sandor and Moreno-Hagelsieb, Gabriel and Parkinson, John and Segre, Daniel and Babu, Mohan and Kozakov, Dima and Emili, Andrew} } @article {289, title = {Structure and Toxicity Characterization of Alkyl Hydroxylated Metabolites of 6PPD-Q.}, journal = {Environ Sci Technol}, year = {2025}, month = {2025 Apr 08}, abstract = {

Distinct from other nontoxic phenyl--phenylenediamine (PPD) quinones, -(1,3-dimethylbutyl)-{\textquoteright}-phenyl--phenylenediamine-quinone (6PPD-Q) was recently discovered to be regioselectively metabolized to alkyl hydroxylated metabolites (alkyl-OH-6PPD-Q) in rainbow trout. It remains unknown whether the unique alkyl-OH-6PPD-Q contributes to the toxicity of 6PPD-Q. To test this, we herein synthesized chemical standards of alkyl-OH-6PPD-Q isomers and investigated their metabolic formation mechanism and toxicity. The predominant alkyl-OH-6PPD-Q was confirmed to be hydroxylated on the C tertiary carbon (C-OH-6PPD-Q). The formation of C-OH-6PPD-Q was only observed in microsomal but not in cytosolic fractions of rainbow trout () liver S9. A general cytochrome P450 (CYP450) inhibitor fluoxetine inhibited the formation of hydroxylated metabolites of 6PPD-Q, supporting that CYP450 catalyzed the hydroxylation. This well-explained the compound- and regio-selective formation of C-OH-6PPD-Q, due to the weak C-H bond on the C tertiary carbon. Surprisingly, while cytotoxicity was observed for 6PPD-Q and C-OH-6PPD-Q in a coho salmon () embryo (CSE-119) cell line, no toxicity was observed for C-OH-6PPD-Q. To further confirm this under physiologically relevant conditions, we fractionated 6PPD-Q metabolites formed in the liver microsome of rainbow trout. Cytotoxicity was observed for the fraction of 6PPD-Q, but not the fraction of C-OH-6PPD-Q. In summary, this study highlighted the C tertiary carbon as the key moiety for both metabolism and toxicity of 6PPD-Q and confirmed that alkyl hydroxylation is a detoxification pathway for 6PPD-Q.

}, issn = {1520-5851}, doi = {10.1021/acs.est.4c11823}, author = {Nair, Pranav and Barrett, Holly and Tanoto, Kaylin and Xie, Linna and Sun, Jianxian and Yang, Diwen and Yao, Han and Song, Datong and Peng, Hui} } @article {290, title = {Synthesis and Toxicity Evaluation of -Phenylenediamine-Quinones.}, journal = {Environ Sci Technol}, year = {2025}, month = {2025 Apr 08}, abstract = {

-(1,3-Dimethylbutyl)--phenyl--phenylenediamine-quinone (6PPD-Q), the tire rubber-derived transformation product of 6PPD, was recently discovered to cause the acute mortality of coho salmon (). Aiming to identify potential replacement antiozonants for 6PPD that do not produce toxic quinones, seven PPD-quinones with distinct side chains were synthesized to investigate their structure-related toxicities using rainbow trout (). While 6PPD-Q exerted high toxicity (96 h LC = 0.35 μg/L), toxicity was not observed for six other PPD-quinones despite their similar structures. The fish tissue concentrations of 6PPD-Q after sublethal exposure (0.29 μg/L) were comparable to the other PPD-quinones, which indicated that bioaccumulation levels were not the reason for the selective toxicity of 6PPD-Q. Hydroxylated PPD-quinones were detected as the predominant metabolites in fish tissue. Interestingly, a single major aromatic hydroxylation metabolite was detected for the alternate PPD-quinones, but two abundant OH-6PPD-Q isomers were detected for 6PPD-Q. MS spectra confirmed that hydroxylation occurred on the alkyl side chain for one isomer. The structurally selective toxicity of 6PPD-Q was also observed in a coho salmon (CSE-119) cell line, which further supports its intrinsic toxicity. This study reported the selective toxicity of 6PPD-Q and pinpointed the possibility for other PPDs to be applied as potential substitutes of 6PPD.

}, issn = {1520-5851}, doi = {10.1021/acs.est.4c12220}, author = {Nair, Pranav and Sun, Jianxian and Xie, Linna and Kennedy, Lisa and Kozakiewicz, Derek and Kleywegt, Sonya M and Hao, Chunyan and Byun, Hannah and Barrett, Holly and Baker, Joshua and Monaghan, Joseph and Krogh, Erik T and Song, Datong and Peng, Hui} } @article {277, title = {Compound Class-Specific Temporal Trends (2021{\textendash}2023) of Tire Wear Compounds in Suspended Solids from Toronto Wastewater Treatment Plants}, journal = {ACS ES\&T Water}, year = {2024}, month = {11/2024}, author = {Xie, Linna and Yuan, Lai and Sun, Jianxian and Yang, Miqing and Khan, Ismail and Lopez, Joselyn and Gong, Yufeng and Nair, Pranav and Hao, Chunyan and Helm, Paul and Barrett, Holly and Edwards, Elizabeth and Peng, Hui} } @article {263, title = {Diindoles produced from commensal microbiota metabolites function as endogenous CAR/Nr1i3 ligands}, journal = {Nature Communications}, year = {2024}, author = {Liu, Jiabao and Malekoltojari, Aniaz and Asokakumar, Anjana and Chow, Vimanda and Li, Linhao and Li, Hao and Grimaldi, Marina and Dang, Nathanlown and Campbell, Jhenielle and Barrett, Holly and Sun, Jianxian and Navarre, William and Wilson, Derek and Wang, Hongbing and Mani, Sridhar and Balaguer, Patrick and Anakk, Sayeepriyadarshini and Peng, Hui* and Krause, Henry*} } @article {275, title = {Emerging investigator series: nontargeted screening of aryl hydrocarbon receptor agonists in endangered beluga whales from the St. Lawrence Estuary: beyond legacy contaminants.}, journal = {Environ Sci Process Impacts}, volume = {26}, year = {2024}, month = {2024 Sep 18}, pages = {1451-1464}, abstract = {

The elevated concentrations of organohalogen contaminants in the endangered St. Lawrence Estuary (SLE) belugas have prompted the hypothesis that aryl hydrocarbon receptor (AhR) activity may be a contributor towards their potential adverse effects. While indirect associations between AhR and contaminant levels have been reported in SLE beluga tissues, AhR activity was never directly measured. Using bioassays and nontargeted analysis, this study contrasted AhR activity and agonist profiles between pooled tissue extracts of endangered SLE and non-threatened Arctic belugas. Tissue extracts of SLE belugas exhibited significantly higher overall AhR activity than that of Arctic belugas, with a 2000s SLE beluga liver extract exerting significantly higher activity than blubber extracts of SLE and Arctic belugas from the same time period. Contrary to our expectations, well-known AhR agonists detected by nontargeted analysis, including polychlorinated biphenyls (PCBs), were only minor contributors to the observed AhR activity. Instead, Tox21 suspect screening identified more polar chemicals, such as dyes and natural indoles, as potential contributors. Notably, the natural product bromoindole was selectively detected in SLE beluga liver at high abundance and was further confirmed as an AhR agonist. These findings highlighted the significance of the AhR-mediated toxicity pathway in belugas and underscored the importance of novel AhR agonists, particularly polar compounds, in its induction.

}, keywords = {Animals, Beluga Whale, Endangered Species, Environmental Monitoring, Estuaries, Liver, Polychlorinated Biphenyls, Receptors, Aryl Hydrocarbon, Water Pollutants, Chemical}, issn = {2050-7895}, doi = {10.1039/d4em00243a}, author = {Barrett, Holly and Sun, Jianxian and Chen, Yuhao and Yang, Diwen and Verreault, Jonathan and Houde, Magali and Wania, Frank and Peng, Hui} } @article {269, title = {Identification of environmental and methodological factors driving variability of Pepper Mild Mottle Virus (PMMoV) across three wastewater treatment plants in the City of Toronto.}, journal = {Sci Total Environ}, volume = {932}, year = {2024}, month = {2024 Jul 01}, pages = {172917}, abstract = {

PMMoV has been widely used to normalize the concentration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, influenza, and respiratory syncytial virus (RSV) to account for variations in the fecal content of wastewater. PMMoV is also used as an internal RNA recovery control for wastewater-based epidemiology (WBE) tests. While potentially useful for the interpretation of WBE data, previous studies have suggested that PMMoV concentration can be affected by various physico-chemical characteristics of wastewater. There is also the possibility that laboratory methods, particularly the variability in centrifugation steps to remove supernatant from pellets can cause PMMoV variability. The goal of this study is to improve our understanding of the main drivers of PMMoV variability by assessing the relationship between PMMoV concentration, the physico-chemical characteristics of wastewater, and the methodological approach for concentrating wastewater samples. We analyzed 24-hour composite wastewater samples collected from the influent stream of three wastewater treatment plants (WWTPs) located in the City of Toronto, Ontario, Canada. Samples were collected 3 to 5 times per week starting from the beginning of March 2021 to mid-July 2023. The influent flow rate was used to partition the data into wet and dry weather conditions. Physico-chemical characteristics (e.g., total suspended solids (TSS), biological oxygen demand (BOD), alkalinity, electrical conductivity (EC), and ammonia (NH)) of the raw wastewater were measured, and PMMoV was quantified. Spatial and temporal variability of PMMoV was observed throughout the study period. PMMoV concentration was significantly higher during dry weather conditions. Multiple linear regression analysis demonstrates that the number and type of physico-chemical parameters that drive PMMoV variability are site-specific, but overall BOD and alkalinity were the most important predictors. Differences in PMMoV concentration for a single WWTP between two different laboratory methods, along with a weak correlation between pellet mass and TSS using one method may indicate that differences in sample concentration and subjective subsampling bias could alter viral recovery and introduce variability to the data.

}, keywords = {Environmental Monitoring, Ontario, Tobamovirus, Waste Disposal, Fluid, Wastewater}, issn = {1879-1026}, doi = {10.1016/j.scitotenv.2024.172917}, author = {Goitom, Eyerusalem and Ariano, Sarah and Gilbride, Kim and Yang, Minqing Ivy and Edwards, Elizabeth A and Peng, Hui and Dannah, Nora and Farahbakhsh, Farnaz and Hataley, Eden and Sarvi, Hooman and Sun, Jianxian and Waseem, Hassan and Oswald, Claire} } @article {271, title = {Identification of Hydrocarbon Sulfonates as Previously Overlooked Transthyretin Ligands in the Environment.}, journal = {Environ Sci Technol}, year = {2024}, month = {2024 May 30}, abstract = {

Incidences of thyroid disease, which has long been hypothesized to be partially caused by exposure to thyroid hormone disrupting chemicals (TDCs), have rapidly increased in recent years. However, known TDCs can only explain a small portion (\~{}1\%) of human transthyretin (hTTR) binding activities in environmental samples, indicating the existence of unknown hTTR ligands. In this study, we aimed to identify the major environmental hTTR ligands by employing protein ffinity urification with ontargeted nalysis (APNA). hTTR binding activities were detected in all 11 indoor dust and 9 out of 10 sewage sludge samples by the FITC-T displacement assay. By using APNA, 31 putative hTTR ligands were detected including perfluorooctanesulfonate (PFOS). Two of the most abundant ligands were identified as hydrocarbon surfactants ( dodecyl benzenesulfonate). Moreover, another abundant ligand was surprisingly identified as a disulfonate fluorescent brightener, 4,4{\textquoteright}-bis(2-sulfostyryl)biphenyl sodium (CBS). CBS was validated as a nM-affinity hTTR ligand with an IC of 345 nM. In total, hydrocarbon surfactants and fluorescent brighteners explain 1.92-17.0 and 5.74-54.3\% of hTTR binding activities in dust and sludge samples, respectively, whereas PFOS only contributed \<0.0001\%. Our study revealed for the first time that hydrocarbon sulfonates are previously overlooked hTTR ligands in the environment.

}, issn = {1520-5851}, doi = {10.1021/acs.est.3c10973}, author = {Gong, Yufeng and Sun, Jianxian and Wang, Xiaoyun and Barrett, Holly and Peng, Hui} } @article {276, title = {Structurally Selective Ozonolysis of -Phenylenediamines and Toxicity in Coho Salmon and Rainbow Trout.}, journal = {Environ Sci Technol}, year = {2024}, month = {2024 Nov 23}, abstract = {

The tire-rubber-derived ozonation product of -(1,3-dimethylbutyl)-{\textquoteright}-phenyl--phenylenediamine (6PPD), -(1,3-dimethylbutyl)-{\textquoteright}-phenyl--phenylenediamine-quinone (6PPD-Q), was recently discovered to cause acute mortality in coho salmon (). -Phenylenediamines (PPDs) with variable side chains distinct from 6PPD have been identified as potential replacement antioxidants, but their toxicities remain unclear under environmentally relevant ozone conditions. We herein tested the multiphase gas-surface ozone reactivity of four select PPDs [6PPD, -isopropyl-{\textquoteright}-phenyl--phenylenediamine (IPPD), ,{\textquoteright}-diphenyl--phenylenediamine (DPPD), and -phenyl-{\textquoteright}-cyclohexyl--phenylenediamine (CPPD)] and evaluated the toxicity of their reaction mixtures in coho salmon, rainbow trout (), and fathead minnow (). 6PPD and IPPD were found to rapidly react with ozone, while no significant multiphase ozone reactivity was observed for DPPD or CPPD. The viability of coho salmon CSE-119 cells was strongly affected by the ozonolysis products of 6PPD but not by those of the other three PPDs. Acute mortality was only observed in juvenile rainbow trout that were exposed to oxidized 6PPD, suggesting a common mechanism of toxic action in the two salmonid fish species. This study reports the structurally selective ozone reactivity of PPDs and the unique toxicity of 6PPD ozonolysis mixtures, which demonstrates that other PPDs are potential alternative antioxidants.

}, issn = {1520-5851}, doi = {10.1021/acs.est.4c04817}, author = {Xie, Linna and Yu, Jie and Nair, Pranav and Sun, Jianxian and Barrett, Holly and Meek, Oliver and Qian, Xing and Yang, Diwen and Kennedy, Lisa and Kozakiewicz, Derek and Hao, Chunyan and Hansen, John D and Greer, Justin B and Abbatt, Jonathan P D and Peng, Hui} } @article {270, title = {Underestimation of SARS-CoV-2 in wastewater due to single or double mutations in the N1 qPCR probe binding region.}, journal = {Water Res X}, volume = {22}, year = {2024}, month = {2024 Jan 01}, pages = {100221}, abstract = {

Wastewater surveillance using RT-qPCR has now been widely adopted to track circulating levels of SARS-CoV-2 virus in many sewersheds. The CDC qPCR assays targeting two regions (N1 and N2) within the N gene are commonly used, but a discrepancy between the two biomarkers has been noticed by independent studies using these methods since late 2021. The reason is presumed to be due to mutations in regions targeted by the N1 qPCR probe. In this study, we systematically investigated and unequivocally confirmed that the underlying reason for this discrepancy was mutations in the N1 probe target, and that a single mutation could cause a significant drop in signal. We first confirmed the proportion of related mutations in wastewater samples (Jan 2021-Dec 2022) using nested PCR and LC-MS. Based on relative proportions of N1 alleles, we separated the wastewater data into four time periods corresponding to different variant waves: Period I (Alpha and Delta waves with 0 mutation), Period II (BA.1/BA.2 waves with a single mutation found in all Omicron strains), Period III (BA.5.2* wave with two mutations), and Period IV (BQ.1* wave with two mutations). Significantly lower N1 copies relative to N2 copies in samples from Periods II-IV compared to those from Period I was observed in wastewater. To further pinpoint the extent to which each mutation impacted N1 quantification, we compared the qPCR response among different synthetic oligomers with corresponding mutations. This study highlighted the impact of even just one or two mutations on qPCR-based wastewater surveillance of SARS-CoV-2.

}, issn = {2589-9147}, doi = {10.1016/j.wroa.2024.100221}, author = {Sun, Jianxian and Yang, Minqing Ivy and Peng, Jiaxi and Khan, Ismail and Lopez, Jhoselyn Jaramillo and Chan, Ronny and Edwards, Elizabeth A and Peng, Hui} } @article {237, title = {Disclosing Environmental Ligands of L-FABP and PPARγ: Should We Re-evaluate the Chemical Safety of Hydrocarbon Surfactants?}, journal = {Environ Sci Technol}, year = {2023}, month = {2023 Aug 01}, abstract = {

Chemical contaminants can cause adverse effects by binding to the liver-fatty acid binding protein (L-FABP) and peroxisome proliferator-activated nuclear receptor γ (PPARγ), which are vital in lipid metabolism. However, the presence of numerous compounds in the environment has hindered the identification of their ligands, and thus only a small portion have been discovered to date. In this study, protein ffinity urification with ontargeted nalysis (APNA) was employed to identify the ligands of L-FABP and PPARγ in indoor dust and sewage sludge. A total of 83 nonredundant features were pulled-out by His-tagged L-FABP as putative ligands, among which 13 were assigned as fatty acids and hydrocarbon surfactants. In contrast, only six features were isolated when His-tagged PPARγ LBD was used as the protein bait. The binding of hydrocarbon surfactants to L-FABP and PPARγ was confirmed using both recombinant proteins and reporter cells. These hydrocarbon surfactants, along with \>50 homologues and isomers, were detected in dust and sludge at high concentrations. Fatty acids and hydrocarbon surfactants explained the majority of L-FABP (57.7 {\textpm} 32.9\%) and PPARγ (66.0 {\textpm} 27.1\%) activities in the sludge. This study revealed hydrocarbon surfactants as the predominant synthetic ligands of L-FABP and PPARγ, highlighting the importance of re-evaluating their chemical safety.

}, issn = {1520-5851}, doi = {10.1021/acs.est.3c02898}, author = {Gong, Yufeng and Yang, Diwen and Liu, Jiabao and Barrett, Holly and Sun, Jianxian and Peng, Hui} } @article {186, title = {Behaviors and trophodynamics of o,p{\textquoteright}-dichlorodiphenyltrichloroethane (o,p{\textquoteright}-DDT) in the aquatic food web: Comparison with p,p{\textquoteright}-DDT.}, journal = {Sci Total Environ}, year = {2022}, month = {2022 Jan 26}, pages = {153447}, abstract = {

The broad-spectrum insecticide p,p{\textquoteright}-dichlorodiphenyltrichloroethane (p,p{\textquoteright}-DDT) has been banned in most countries since the 1970s on account of its environmental persistence as well as the high biomagnification of its major metabolite 1,1-dichloro-2,2-bis(4-chorophenyl)ethylene (p,p{\textquoteright}-DDE). However, the information on the bioaccumulation and behavior of p,p{\textquoteright}-DDTs in aquatic organisms is lacking. In this study, all 6 DDT isomers were detected in biota from the food web of the Liaodong Bay, China, and the total concentrations of DDT isomers in Chinese anchovy (Thrissa kammalensis) and Japanese Spanish mackerel (Scomberomrus niphonius) were 223 {\textpm} 42 ng/g ww and 242 {\textpm} 70 ng/g ww, respectively. In biota, o,p{\textquoteright}-DDD dominated among the o,p{\textquoteright}-isomers (80.5 {\textpm} 17.3\%), while p,p{\textquoteright}-DDE dominated among the p,p{\textquoteright}-isomers (61.8 {\textpm} 15.2\%). Contrastingly, sediment from the Liaodong Bay contained similar proportions of o,p{\textquoteright}-DDT and p,p{\textquoteright}-DDTs, suggesting an isomer-specific metabolism of the compounds in biota. A well-controlled laboratory exposure experiment with Japanese medaka (Oryzias latipes) demonstrated that o,p{\textquoteright}-DDT was more difficult to metabolize to o,p{\textquoteright}-DDE compared with that of p,p{\textquoteright}-DDT. Significantly positive regressions were found between trophic levels and lipid equivalent concentrations for both o,p{\textquoteright}-DDT and o,p{\textquoteright}-DDD, and the trophic magnification factors (TMFs) were estimated as 12.3 and 9.12 (p \< 0.05), respectively. The TMFs of o,p{\textquoteright}-DDT and o,p{\textquoteright}-DDD in the aquatic food web were higher than p,p{\textquoteright}-DDT (7.76), p,p{\textquoteright}-DDD (4.17), and p,p{\textquoteright}-DDE (3.39), which may be explained by the isomer-specific metabolism differences in biota.

}, issn = {1879-1026}, doi = {10.1016/j.scitotenv.2022.153447}, author = {Sun, Jianxian and Xu, Chenke and Peng, Hui and Wan, Yi and Luo, Kai and Barrett, Holly and Hu, Jianying} } @article {217, title = {Defining the Chemical Additives Driving In Vitro Toxicities of Plastics}, journal = {Environ. Sci. Technol.}, year = {2022}, author = {Chen, Wanzhen and Gong, Yufeng and Michael, McKie and Husein, Almuhtaram and Sun, Jianxian and Barrett, Holly and Yang, Diwen and Wu, Menghong and Andrews, Robert and Peng, Hui} } @article {196, title = {Triclosan is the Predominant Antibacterial Compound in Ontario Sewage Sludge}, journal = {Environmental Science and Technology}, volume = {56}, year = {2022}, author = {Barrett, Holly and Sun, Jianxian and Gong, Yufeng and Yang, Paul and Hao, Chunyan and Verreault, Jonathan and Zhang, Yu and Peng, Hui} } @article {212, title = {Wastewater to clinical case (WC) ratio of COVID-19 identifies insufficient clinical testing, onset of new variants of concern and population immunity in urban communities.}, journal = {Sci Total Environ}, year = {2022}, month = {2022 Sep 03}, pages = {158547}, abstract = {

Clinical testing has been the cornerstone of public health monitoring and infection control efforts in communities throughout the COVID-19 pandemic. With the anticipated reduction of clinical testing as the disease moves into an endemic state, SARS-CoV-2 wastewater surveillance (WWS) will have greater value as an important diagnostic tool. An in-depth analysis and understanding of the metrics derived from WWS is required to interpret and utilize WWS-acquired data effectively (McClary-Gutierrez et al., 2021; O{\textquoteright}Keeffe, 2021). In this study, the SARS-CoV-2 wastewater signal to clinical cases (WC) ratio was investigated across seven cities in Canada over periods ranging from 8 to 21 months. This work demonstrates that significant increases in the WC ratio occurred when clinical testing eligibility was modified to appointment-only testing, identifying a period of insufficient clinical testing (resulting in a reduction to testing access and a reduction in the number of daily tests) in these communities, despite increases in the wastewater signal. Furthermore, the WC ratio decreased significantly in 6 of the 7 studied locations, serving as a potential signal of the emergence of the Alpha variant of concern (VOC) in a relatively non-immunized community (40-60 \% allelic proportion), while a more muted decrease in the WC ratio signaled the emergence of the Delta VOC in a relatively well-immunized community (40-60 \% allelic proportion). Finally, a significant decrease in the WC ratio signaled the emergence of the Omicron VOC, likely because of the variant{\textquoteright}s greater effectiveness at evading immunity, leading to a significant number of new reported clinical cases, even when community immunity was high. The WC ratio, used as an additional monitoring metric, could complement clinical case counts and wastewater signals as individual metrics in its potential ability to identify important epidemiological occurrences, adding value to WWS as a diagnostic technology during the COVID-19 pandemic and likely for future pandemics.

}, issn = {1879-1026}, doi = {10.1016/j.scitotenv.2022.158547}, author = {D{\textquoteright}Aoust, Patrick M and Tian, Xin and Towhid, Syeda Tasneem and Xiao, Amy and Mercier, Elisabeth and Hegazy, Nada and Jia, Jian-Jun and Wan, Shen and Kabir, Md Pervez and Fang, Wanting and Fuzzen, Meghan and Hasing, Maria and Yang, Minqing Ivy and Sun, Jianxian and Plaza-Diaz, Julio and Zhang, Zhihao and Cowan, Aaron and Eid, Walaa and Stephenson, Sean and Servos, Mark R and Wade, Matthew J and MacKenzie, Alex E and Peng, Hui and Edwards, Elizabeth A and Pang, Xiao-Li and Alm, Eric J and Graber, Tyson E and Delatolla, Robert} } @article {183, title = {Ecological Role of 6OH-BDE47: Is It a Chemical Offence Molecule Mediated by Enoyl-ACP Reductases?}, journal = {Environ. Sci. Technol.}, year = {2021}, author = {Sun, Jianxian and Barrett, Holly and Hall, David and Kutarna, Steven and Wu, Xiaoqin and Wang, Yan and Peng, Hui} } @article {140, title = {Proteome-wide effects of naphthalene-derived secondary organic aerosol in BEAS-2B cells are caused by short-lived unsaturated carbonyls.}, journal = {Proc Natl Acad Sci U S A}, year = {2020}, month = {2020 Sep 28}, abstract = {

Exposure to air pollution causes adverse health outcomes, but the toxicity mechanisms remain unclear. Here, we investigated the dynamic toxicities of naphthalene-derived secondary organic aerosol (NSOA) in a human bronchial epithelial cell line (BEAS-2B) and identified the chemical components responsible for toxicities. The chemical composition of NSOA was found to vary with six simulated atmospheric aging conditions (C-C), as characterized by high-resolution mass spectrometry and ion mobility mass spectrometry. Global proteome profiling reveals dynamic evolution in toxicity: Stronger proteome-wide impacts were detected in fresh NSOA, but the effects declined along with atmospheric aging. While Nrf2-regulated proteins (e.g., ) were significantly up-regulated, the majority (78 to 97\%) of proteins from inflammation and other pathways were down-regulated by NSOA exposure (e.g., ). This pattern is distinct from the reactive oxygen species (ROS)-mediated toxicity pathway, and an alternative cysteine reaction pathway was revealed by the decreased abundance of proteins (e.g., ) prone to posttranslational thiol modification. This pathway was further validated by observing decreased Nrf2 response in reporter cells, after preincubating NSOA with cysteine. Ethynyl-naphthalene probe was employed to confirm the alkylation of cellular proteome thiols on the proteome-wide level by fresh NSOA via in-gel fluorescence imaging. Nontarget analysis identified several unsaturated carbonyls, including naphthoquinones and hydroxylated naphthoquinones, as the toxic components responsible for cysteine reactivity. Our study provides insights into the dynamic toxicities of NSOA during atmospheric aging and identifies short-lived unsaturated carbonyls as the predominant toxic components at the posttranslational level.

}, issn = {1091-6490}, doi = {10.1073/pnas.2001378117}, author = {Han, Jiajun and Wang, Shunyao and Yeung, Kirsten and Yang, Diwen and Gu, Wen and Ma, Zhiyuan and Sun, Jianxian and Wang, Xiaomin and Chow, Chung-Wai and Chan, Arthur W H and Peng, Hui} } @article {130, title = {Toxicokinetics of Brominated Azo Dyes in the Early Life Stages of Zebrafish () Is Prone to Aromatic Substituent Changes.}, journal = {Environ Sci Technol}, volume = {54}, year = {2020}, month = {2020 04 07}, pages = {4421-4431}, abstract = {

Brominated azo dyes (BADs) have been identified as predominant indoor brominated pollutants in daycare dust; thus, their potential health risk to children is of concern. However, the toxicities of BADs remain elusive. In this study, the toxicokinetics of two predominant BADs, Disperse Blue 373 (DB373) and Disperse Violet 93 (DV93), and their suspect metabolite 2-bromo-4,6-dinitroaniline (BDNA) was investigated in embryos of zebrafish (). The bioconcentration factor of DV93 at 120 hpf is 6.2-fold lower than that of DB373. The nontarget analysis revealed distinct metabolism routes between DB373 and DV93 by reducing nitro groups to nitroso (DB373) or amine (DV93), despite their similar structures. NAD(P)H quinone oxidoreductase 1 (NQO1) and pyruvate dehydrogenase were predicted as the enzymes responsible for the reduction of DB373 and DV93 by correlating time courses of the metabolites and enzyme development. Further in vitro recombinant enzyme and in vivo inhibition results validated NQO1 as the enzyme specifically reducing DB373, but not DV93. Global proteome profiling revealed that the expression levels of proteins from the "apoptosis-induced DNA fragmentation" pathway were significantly upregulated by all three BADs, supporting the bioactivation of BADs to mutagenic aromatic amines. This study discovered the bioactivation of BADs via distinct eukaryotic enzymes, implying their potential health risks.

}, keywords = {Animals, Azo Compounds, Child, Dust, Embryo, Nonmammalian, Humans, Mutagens, Toxicokinetics, Zebrafish}, issn = {1520-5851}, doi = {10.1021/acs.est.9b07178}, author = {Han, Jiajun and Yang, Diwen and Hall, David Ross and Liu, Jiabao and Sun, Jianxian and Gu, Wen and Tang, Song and Alharbi, Hattan A and Jones, Paul D and Krause, Henry M and Peng, Hui} } @article {92, title = {Hydroxylated 2-Ethylhexyl tetrabromobenzoate isomers in house dust and their agonistic potencies with several nuclear receptors.}, journal = {Environ Pollut}, volume = {227}, year = {2017}, month = {2017 Aug}, pages = {578-586}, abstract = {

In the current study, by combining ultra-high resolution (UHR) MS spectra, MS spectra, and derivatization, three hydroxylated isomers of 2-ethylhexyl tetrabromobenzoate (OH-TBB) were identified in Firemaster 550 and BZ-54 technical products. Also, a new LC-UHRMS method, using atmospheric pressure chemical ionization (APCI), was developed for simultaneous analysis of OH-TBB, TBB, hydroxylated bis(2-ethylhexyl)-tetrabromophthalate (OH-TBPH) and TBPH in 23 samples of dust collected from houses in Saskatoon, SK, Canada. OH-TBBs were detected in 91\% of samples, with a geometric mean concentration of 0.21\ ng/g, which was slightly less than those of OH-TBPH (0.35\ ng/g). TBB was detected in 100\% of samples of dust with a geometric mean concentration of 992\ ng/g. Significant (p\ \<\ 0.001) log-linear relationships between concentrations of OH-TBBs, TBB, or OH-TBPHs and TBPH in dust support the hypothesis of a common source of these compounds. OH-TBBs were found to be strong agonists of peroxisome proliferator-activated receptor gamma (PPARγ) and weaker agonists of the estrogen receptor (ER), but no agonistic potencies was observed with the androgen receptor (AR). Occurrence of OH-TBBs in technical products and house dust, together with their relatively strong PPARγ potencies, indicated their potential risk to health of humans.

}, keywords = {Air Pollution, Indoor, Bromobenzoates, Canada, Dust, Environmental Monitoring, Flame Retardants, Halogenated Diphenyl Ethers, Humans}, issn = {1873-6424}, doi = {10.1016/j.envpol.2017.04.094}, author = {Peng, Hui and Sun, Jianxian and Saunders, David M V and Codling, Garry and Wiseman, Steve and Jones, Paul D and Giesy, John P} } @article {93, title = {Identification of Chemicals that Cause Oxidative Stress in Oil Sands Process-Affected Water.}, journal = {Environ Sci Technol}, volume = {51}, year = {2017}, month = {2017 Aug 01}, pages = {8773-8781}, abstract = {

Oil sands process-affected water (OSPW) has been reported to cause oxidative stress in organisms, yet the causative agents remain unknown. In this study, a high-throughput in vitro Nrf2 reporter system was used, to determine chemicals in OSPW that cause oxidative stress. Five fractions, with increasing polarity, of the dissolved organic phase of OSPW were generated by use of solid phase extraction cartridges. The greatest response of Nrf2 was elicited by F2 (2.7 {\textpm} 0.1-fold), consistent with greater hydroperoxidation of lipids in embryos of Japanese medaka (Oryzias latipes) exposed to F2. Classic naphthenic acids were mainly eluted in F1, and should not be causative chemicals. When F2 was fractionated into 60 subfractions by use of HPLC, significant activation of Nrf2 was observed in three grouped fractions: F2.8 (1.30 {\textpm} 0.01-fold), F2.16 (1.34 {\textpm} 0.05-fold), and F2.25 (1.28 {\textpm} 0.15-fold). 54 compounds were predicted to be potential chemicals causing Nrf2 response, predominated by SO and O species. By use of high-resolution MS spectra, these SO and O species were identified as hydroxylated aldehydes. This study demonstrated that polyoxygenated chemicals, rather than classic NAs, were the major chemicals responsible for oxidative stress in the aqueous phase of OSPW.

}, keywords = {Animals, Carboxylic Acids, Oil and Gas Fields, Oryzias, Oxidative Stress, Water, Water Pollutants, Chemical}, issn = {1520-5851}, doi = {10.1021/acs.est.7b01987}, author = {Sun, Jianxian and Peng, Hui* and Alharbi, Hattan A and Jones, Paul D and Giesy, John P and Wiseman, Steve B} } @article {100, title = {Combined Transcriptomic and Proteomic Approach to Identify Toxicity Pathways in Early Life Stages of Japanese Medaka (Oryzias latipes) Exposed to 1,2,5,6-Tetrabromocyclooctane (TBCO).}, journal = {Environ Sci Technol}, volume = {50}, year = {2016}, month = {2016 07 19}, pages = {7781-90}, abstract = {

Currently, the novel brominated flame retardant 1,2,5,6-tetrabromocyclooctane (TBCO) is considered a potential replacement for hexabromocyclododecane (HBCD). Therefore, use of TBCO could increase in the near future. To assess potential toxicological risks to aquatic organisms, embryos of Japanese medaka (Oryzias latipes) were exposed to 10, 100, or 1000 μg/L TBCO from 2 h postfertilization until 1 day post-hatch. TBCO accumulated in embryos in the order of 0.43-1.3 {\texttimes} 10(4)-fold, and the rate constant of accumulation was 1.7-1.8 per day. The number of days to hatch and the hatching success of embryos exposed to the medium and the greatest concentrations of TBCO were impaired. Responses of the transcriptome (RNA-seq) and proteome were characterized in embryos exposed to 100 μg/L TBCO because this was the least concentration of TBCO that caused an effect on hatching. Consistent with effects on hatching, proteins whose abundances were reduced by exposure to TBCO were enriched in embryo development and hatching pathways. Also, on the basis of the responses of transcriptome and proteome, it was predicted that TBCO might impair vision and contraction of cardiac muscle, respectively, and these effects were confirmed by targeted bioassays. This study provided a comprehensive understanding of effects of TBCO on medaka at early life stages and illustrated the power of "omics" to explain and predict phenotypic responses to chemicals.

}, keywords = {Animals, Oryzias, Proteomics, Water Pollutants, Chemical}, issn = {1520-5851}, doi = {10.1021/acs.est.6b01249}, author = {Sun, Jianxian and Tang, Song and Peng, Hui* and Saunders, David M V and Doering, Jon A and Hecker, Markus and Jones, Paul D and Giesy, John P and Wiseman, Steve} } @article {101, title = {High Conservation in Transcriptomic and Proteomic Response of White Sturgeon to Equipotent Concentrations of 2,3,7,8-TCDD, PCB 77, and Benzo[a]pyrene.}, journal = {Environ Sci Technol}, volume = {50}, year = {2016}, month = {2016 05 03}, pages = {4826-35}, abstract = {

Adverse effects associated with exposure to dioxin-like compounds (DLCs) are mediated primarily through activation of the aryl hydrocarbon receptor (AHR). However, little is known about the cascades of events that link activation of the AHR to apical adverse effects. Therefore, this study used high-throughput, next-generation molecular tools to investigate similarities and differences in whole transcriptome and whole proteome responses to equipotent concentrations of three agonists of the AHR, 2,3,7,8-TCDD, PCB 77, and benzo[a]pyrene, in livers of a nonmodel fish, the white sturgeon (Acipenser transmontanus). A total of 926 and 658 unique transcripts were up- and down-regulated, respectively, by one or more of the three chemicals. Of the transcripts shared by responses to all three chemicals, 85\% of up-regulated transcripts and 75\% of down-regulated transcripts had the same magnitude of response. A total of 290 and 110 unique proteins were up- and down-regulated, respectively, by one or more of the three chemicals. Of the proteins shared by responses to all three chemicals, 70\% of up-regulated proteins and 48\% of down-regulated proteins had the same magnitude of response. Among treatments there was 68\% similarity between the global transcriptome and global proteome. Pathway analysis revealed that perturbed physiological processes were indistinguishable between equipotent concentrations of the three chemicals. The results of this study contribute toward more completely describing adverse outcome pathways associated with activation of the AHR.

}, keywords = {Animals, Benzo(a)pyrene, Dioxins, Fishes, Polychlorinated Dibenzodioxins, Proteomics}, issn = {1520-5851}, doi = {10.1021/acs.est.6b00490}, author = {Doering, Jon A and Tang, Song and Peng, Hui and Eisner, Bryanna K and Sun, Jianxian and Giesy, John P and Wiseman, Steve and Hecker, Markus} } @article {95, title = {Mutagenic Azo Dyes, Rather Than Flame Retardants, Are the Predominant Brominated Compounds in House Dust.}, journal = {Environ Sci Technol}, volume = {50}, year = {2016}, month = {2016 12 06}, pages = {12669-12677}, abstract = {

Characterization of toxicological profiles by use of traditional targeted strategies might underestimate the risk of environmental mixtures. Unbiased identification of prioritized compounds provides a promising strategy for meeting regulatory needs. In this study, untargeted screening of brominated compounds in house dust was conducted using a data-independent precursor isolation and characteristic fragment (DIPIC-Frag) approach, which used data-independent acquisition (DIA) and a chemometric strategy to detect peaks and align precursor ions. A total of 1008 brominated compound peaks were identified in 23 house dust samples. Precursor ions and formulas were identified for 738 (73\%) of the brominated compounds. A correlation matrix was used to cluster brominated compounds; three large groups were found for the 140 high-abundance brominated compounds, and only 24 (17\%) of these compounds were previously known flame retardants. The predominant class of unknown brominated compounds was predicted to consist of nitrogen-containing compounds. Following further validation by authentic standards, these compounds (56\%) were determined to be novel brominated azo dyes. The mutagenicity of one major component was investigated, and mutagenicity was observed at environmentally relevant concentrations. Results of this study demonstrated the existence of numerous unknown brominated compounds in house dust, with mutagenic azo dyes unexpectedly being identified as the predominant compounds.

}, keywords = {Azo Compounds, Dust, Flame Retardants, Halogenated Diphenyl Ethers, Hydrocarbons, Brominated, Mutagens}, issn = {1520-5851}, doi = {10.1021/acs.est.6b03954}, author = {Peng, Hui and Saunders, David M V and Sun, Jianxian and Jones, Paul D and Wong, Chris K C and Liu, Hongling and Giesy, John P} } @article {99, title = {Peroxisome Proliferator-Activated Receptor γ is a Sensitive Target for Oil Sands Process-Affected Water: Effects on Adipogenesis and Identification of Ligands.}, journal = {Environ Sci Technol}, volume = {50}, year = {2016}, month = {2016 07 19}, pages = {7816-24}, abstract = {

Identification of toxic components of complex mixtures is a challenge. Here, oil sands process-affected water (OSPW) was used as a case study to identify those toxic components with a known protein target. Organic chemicals in OSPW exhibited dose-dependent activation of peroxisome proliferator-activated receptor γ (PPARγ) at concentrations less than those currently in the environment (0.025{\texttimes} equivalent of full-strength OSPW), by use of a luciferase reporter gene assay. Activation of PPARγ-mediated adipogenesis by OSPW was confirmed in 3T3L1 preadipocytes, as evidenced by accumulation of lipids and up-regulation of AP2, LPL, and PPARγ gene expression after exposure to polar fractions of OSPW. Unexpectedly, the nonpolar fractions of OSPW inhibited differentiation of preadipocytes via activation of the Wnt signaling pathway. Organic chemicals in OSPW that were ligands of PPARγ were identified by use of a pull-down system combined with untargeted chemical analysis (PUCA), with a recombinant PPARγ protein. Thirty ligands of PPARγ were identified by use of the PUCA assay. High resolution MS(1) and MS(2) spectra were combined to predict the formulas or structures of a subset of ligands, and polyoxygenated or heteroatomic chemicals, especially hydroxylated carboxylic/sulfonic acids, were the major ligands of PPARγ.

}, keywords = {Adipogenesis, Ligands, Oil and Gas Fields, PPAR gamma, Water}, issn = {1520-5851}, doi = {10.1021/acs.est.6b01890}, author = {Peng, Hui and Sun, Jianxian and Alharbi, Hattan A and Jones, Paul D and Giesy, John P and Wiseman, Steve} } @article {104, title = {p,p{\textquoteright}-DDE Induces Gonadal Intersex in Japanese Medaka (Oryzias latipes) at Environmentally Relevant Concentrations: Comparison with o,p{\textquoteright}-DDT.}, journal = {Environ Sci Technol}, volume = {50}, year = {2016}, month = {2016 Jan 05}, pages = {462-9}, abstract = {

Previous studies have reported high body burdens of dichlorodiphenyltrichloroethane (DDT) and its metabolites in wild fishes worldwide. This study evaluated the adverse effects of 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p{\textquoteright}-DDE) and o,p{\textquoteright}-DDT on gonadal development and reproduction by exposing transgenic Japanese medaka (Oryzias latipes) from hatch for 100 days. While both p,p{\textquoteright}-DDE and o,p{\textquoteright}-DDT induced intersex in male medaka, the lowest observable effective concentration (LOEC) of o,p{\textquoteright}-DDT was 57.7 ng/g ww, about 5-fold lower than that (272 ng/g ww) of p,p{\textquoteright}-DDE. Since LOECs of both chemicals were comparable to the body concentrations in wild fish, DDT contamination would likely contribute to the occurrence of intersex observed in wild fish. Exposure to o,p{\textquoteright}-DDT resulted in much higher expression of vitellogenin in liver of males than p,p{\textquoteright}-DDE, accordant with the higher potency of o,p{\textquoteright}-DDT than p,p{\textquoteright}-DDE to induce intersex. This phenomenon could be partly explained by the significantly elevated levels of 17β-estradiol in plasma of males exposed to o,p{\textquoteright}-DDT, in addition to its estrogenic activity via the estrogen receptor. Significantly lower fertilization (p = 0.006) and hatchability (p = 0.019) were observed in the 13 intersex males. This study for the first time demonstrated the induction of intersex and reproductive effects of p,p{\textquoteright}-DDE and o,p{\textquoteright}-DDT at environmentally relevant concentrations.

}, keywords = {Animals, DDT, Dichlorodiphenyl Dichloroethylene, Disorders of Sex Development, Estradiol, Gonads, Male, Oryzias, Vitellogenins, Water Pollutants, Chemical}, issn = {1520-5851}, doi = {10.1021/acs.est.5b05042}, author = {Sun, Jianxian and Wang, Chen and Peng, Hui and Zheng, Guomao and Zhang, Shiyi and Hu, Jianying} } @article {103, title = {Untargeted Screening and Distribution of Organo-Bromine Compounds in Sediments of Lake Michigan.}, journal = {Environ Sci Technol}, volume = {50}, year = {2016}, month = {2016 Jan 05}, pages = {321-30}, abstract = {

Previously unreported natural and synthetic organo-bromine compounds (NSOBCs) have been found to contribute more than 99\% of total organic bromine (TOB) in environmental matrices. We recently developed a novel untargeted method (data-independent precursor isolation and characteristic fragment, DIPIC-Frag) and identified \~{}2000 NSOBCs in two sediments from Lake Michigan. In this study, this method was used to investigate the distributions of these NSOBCs in 23 surficial samples and 24 segments of a sediment core from Lake Michigan. NSOBCs were detected in all 23 surficial samples and exhibited 10- to 100-fold variations in peak abundance among locations. The pattern of distributions of NSOBCs was correlated with depth of the water column (r(2) = 0.61, p \< 0.001). Hierarchical cluster analysis showed that sediments in close proximity exhibited similar profiles of NSOBCs. Distributions of NSOBCs in 24 segments of a sediment core dated from 1766 to 2008 were investigated, and samples from similar depths exhibited similar profiles of NSOBCs. NSOBCs were grouped into four clusters (soft-cluster analysis) with different temporal trends of abundances. 515 and 768 of the NSOBCs were grouped into cluster 1 and cluster 3 with increasing temporal trends, especially since 1950, indicating that abundances of these compounds might have been affected by human activities.

}, keywords = {Bromine Compounds, Environmental Monitoring, Geologic Sediments, Halogenated Diphenyl Ethers, Hydrocarbons, Brominated, Lakes, Michigan, Water Pollutants, Chemical}, issn = {1520-5851}, doi = {10.1021/acs.est.5b04709}, author = {Peng, Hui and Chen, Chunli and Cantin, Jenna and Saunders, David M V and Sun, Jianxian and Tang, Song and Codling, Garry and Hecker, Markus and Wiseman, Steve and Jones, Paul D and Li, An and Rockne, Karl J and Sturchio, Neil C and Giesy, John P} } @article {98, title = {Untargeted Screening and Distribution of Organo-Iodine Compounds in Sediments from Lake Michigan and the Arctic Ocean.}, journal = {Environ Sci Technol}, volume = {50}, year = {2016}, month = {2016 09 20}, pages = {10097-105}, abstract = {

The majority of halogenated organic compounds present in the environment remain unidentified. To address this data gap, we recently developed an untargeted method (data-independent precursor isolation and characteristic fragment; DIPIC-Frag) for identification of unknown organo-bromine compounds. In this study, the method was adapted to enable untargeted screening of natural and synthetic organo-iodine compounds (NSOICs) in sediments. A total of 4,238 NSOIC peaks were detected in sediments from Lake Michigan. Precursor ions and formulas were determined for 2,991 (71\%) of the NSOIC peaks. These compounds exhibited variations in abundances (\<10(3) to \~{}10(7)), m/z values (206.9304-996.9474), retention times (1.0-29.7 min), and number of iodine atoms (1-4). Hierarchical cluster analysis showed that sediments in closer proximity exhibited similar profiles of NSOICs. NSOICs were screened in 10 samples of sediment from the Arctic Ocean to compare the profiles of NSOICs between freshwater and marine sediments. A total of 3,168 NSOIC peaks were detected, and profiles of NSOICs in marine sediments were clearly distinct from Lake Michigan. The coexistence of brominated and iodinated analogues indicated that some NSOICs are of natural origin. Different ratios of abundances of iodinated compounds to brominated analogues were observed and proposed as a marker to distinguish sources of NSOICs.

}, keywords = {Geologic Sediments, Iodine Compounds, Lakes, Michigan, Oceans and Seas, Water Pollutants, Chemical}, issn = {1520-5851}, doi = {10.1021/acs.est.6b03221}, author = {Peng, Hui and Chen, Chunli and Cantin, Jenna and Saunders, David M V and Sun, Jianxian and Tang, Song and Codling, Garry and Hecker, Markus and Wiseman, Steve and Jones, Paul D and Li, An and Rockne, Karl J and Sturchio, Neil C and Cai, Minghong and Giesy, John P} } @article {107, title = {Detection, identification, and quantification of hydroxylated bis(2-ethylhexyl)-tetrabromophthalate isomers in house dust.}, journal = {Environ Sci Technol}, volume = {49}, year = {2015}, month = {2015 Mar 03}, pages = {2999-3006}, abstract = {

Ultra-High Resolution LC/mass spectrometry (LC-UHRMS; Thermo Fisher Q-Exactive) was used to identify two novel isomers of hydroxylated bis(2-ethylhexyl)-tetrabromophthalate (OH-TBPH) which were unexpectedly observed in a commercial standard of TBPH. By combining ultra-high resolution (UHR) mass spectra (MS(1)), mass errors to theoretical [TBPH-Br+O](-) were 2.1 and 1.0 ppm for the two isomers, UHR-MS(2) spectra and NMR analysis; the structures of the two compounds were identified as hydroxylated TBPH with a hydroxyl group on the aromatic ring. Relatively great proportions of the two isomers of OH-TBPH were detected in two technical products, Firemaster 550 (FM-550; 0.1\% and 6.2\%, respectively) and Firemaster BZ 54 (BZ-54; 0.1\% and 7.9\%), compared to a commercial standard (0.4\% and 0.9\%). To simultaneously analyze OH-TBPH isomers and TBPH in samples of dust, a method based on LC-UHRMS was developed to quantify the two compounds, using negative and positive ion modes, respectively. The instrumental limit of detection for TBPH was 0.01 μg/L, which was 200-300 times better than traditional methods (2.5 μg/L) based on gas chromatography-mass spectrometry. The analytical method combined with a Florisil cleanup was successfully applied to analyze TBPH and OH-TBPH in 23 indoor dust samples from Saskatoon, Saskatchewan, Canada. Two OH-TBPH isomers, OH-TBPH1 and OH-TBPH2, were detected in 52\% and 91\% of dust samples, respectively. Concentrations of OH-TBPH2 (0.35 {\textpm} 1.0 ng/g) were 10-fold greater than those of OH-TBPH1 (0.04 {\textpm} 0.88 ng/g) in dust, which was similar to profiles in FM-550 and BZ-54. TBPH was also detected in 100\% of dust samples with a mean concentration of 733 {\textpm} 0.87 ng/g. A significant (p \< 0.001) log-linear relationship was observed between TBPH and OH-TBPH isomers, further supporting the hypothesis of a common source of emission. Relatively small proportions of OH-TBPH isomers were detected in dust (0.01\% {\textpm} 0.67 OH-TBPH1 and 0.1\% {\textpm} 0.60 OH-TBPH2), which were significantly less than those in technical products (p \< 0.001). This result indicated different environmental behaviors of OH-TBPH and TBPH. Detection of isomers of OH-TBPH is important, since compounds with phenolic groups have often shown relatively greater toxicities than nonhydroxylated analogues. Further study is warranted to clarify the environmental behaviors and potential toxicities of OH-TBPH isomers.

}, keywords = {Chromatography, Liquid, Dust, Flame Retardants, Limit of Detection, Mass Spectrometry, Phthalic Acids}, issn = {1520-5851}, doi = {10.1021/es505743d}, author = {Peng, Hui and Saunders, David M V and Sun, Jianxian and Codling, Garry and Wiseman, Steve and Jones, Paul D and Giesy, John P} } @article {105, title = {Untargeted Identification of Organo-Bromine Compounds in Lake Sediments by Ultrahigh-Resolution Mass Spectrometry with the Data-Independent Precursor Isolation and Characteristic Fragment Method.}, journal = {Anal Chem}, volume = {87}, year = {2015}, month = {2015 Oct 20}, pages = {10237-46}, abstract = {

While previous studies have found that unknown natural and synthetic organo-bromine compounds (NSOBCs) contributed more than 99\% of the total organic bromine (Br) in the environment, there was no efficient method for untargeted screening to identify NSOBCs in environmental matrixes. A novel untargeted method for identifying NSOBCs, based on ultrahigh-resolution mass spectrometry (UHRMS) with the Q Exactive instrument was developed. This method included a data-independent precursor isolation and characteristic fragment (DIPIC-Frag) procedure to identify NSOBCs. A total of 180 successive 5-m/z-wide windows were used to isolate precursor ions. This resulted in a sufficient dynamic range and specificity to identify peaks of Br fragment ions for analysis. A total of 2520 peaks of NSOBC compounds containing Br were observed in sediments from Lake Michigan, United States. A new chemometric strategy which combined chromatographic profiles, isotopic peaks, precursor isolation window information, and intensities was used to identify precursor ions and chemical formulas for detecting NSOBCs. Precursor ions for 2163 of the 2520 NSOBCs peaks (86\%) were identified, and chemical formulas for 2071 NSOBCs peaks (82\%) were determined. After exclusion of isotopic peaks, 1593 unique NSOBCs were identified and chemical formulas derived for each. Most of the compounds identified had not been reported previously and had intensities which were 100- to 1000-fold greater than the congeners of polybrominated diphenyl ethers (PBDEs). In extracts of sediments, these compounds exhibited variations in intensities (\<10(3) to \~{}10(8)), m/z values (170.9438-997.5217), retention times on a C18 column (1.0-29.3 min), and the number of Br atoms (1-8). Generally, compounds with greater m/z values had longer retention times and greater numbers of Br atoms. Three compounds were used in a proof-of-concept experiment to demonstrate that structures of some of the screened NSOBCs could be further predicted by combining searching of database libraries and high-resolution MS(2) spectra.

}, keywords = {Databases, Chemical, Geologic Sediments, Hydrocarbons, Brominated, Lakes, Mass Spectrometry}, issn = {1520-6882}, doi = {10.1021/acs.analchem.5b01435}, author = {Peng, Hui and Chen, Chunli and Saunders, David M V and Sun, Jianxian and Tang, Song and Codling, Garry and Hecker, Markus and Wiseman, Steve and Jones, Paul D and Li, An and Rockne, Karl J and Giesy, John P} } @article {112, title = {Isomer-specific accumulation of perfluorooctanesulfonate from (N-ethyl perfluorooctanesulfonamido)ethanol-based phosphate diester in Japanese Medaka (Oryzias latipes).}, journal = {Environ Sci Technol}, volume = {48}, year = {2014}, month = {2014 Jan 21}, pages = {1058-66}, abstract = {

While (N-ethyl perfluorooctanesulfonamido)ethanol (FOSE) -based phosphate diester (diSPAP) has been proposed as a candidate precursor of perfluorooctanesulfonate (PFOS), its potential biotransformation to PFOS has not been verified. Metabolism of diSPAP was investigated in Japanese medaka ( Oryzias latipes ) after exposure in water for 10 days, followed by 10 days of depuration. Branched isomers of diSPAP (B-diSPAP) were preferentially enriched in medaka exposed to diSPAP, with the proportion of branched isomers (BF) ranging from 0.56 to 0.80, which was significantly greater than that in the water to which the medaka were exposed (0.36) (p \< 0.001). This enrichment was due primarily to preferential uptake of B-diSPAP. PFOS together with perfluorooctanesulfonamide (PFOSA), N-ethyl perfluorooctanesulfonamide (NEtFOSA), 2-(perfluorooctanesulfonamido)acetic acid (FOSAA), NEtFOSAA, FOSE, and NEtFOSE were detected in medaka exposed to diSPAP, which indicated the potential for biotransformation of diSPAP to PFOS via multiple intermediates. Due to preferential metabolism of branched isomers, FOSAA and PFOSA exhibited greater BF values (\>0.5) than those of NEtFOSA, NEtFOSAA, and NEtFOSE (\<0.2). Such preferential metabolism of branched isomers along the primary pathway of metabolism and preferential accumulation of B-diSPAP led to enrichment of branched PFOS (B-PFOS) in medaka. Enrichment of B-PFOS was greater for 3-, 4-, and 5-perfluoromethyl PFOS (P3MPFOS, P4MPFOS, and P5MPFOS), for which values of BF were 0.58 {\textpm} 0.07, 0.62 {\textpm} 0.06, and 0.61 {\textpm} 0.05 (day 6), respectively; these values are 5.8-, 7.8-, and 6.4-fold greater than those of technical PFOS. This work provides evidence on the isomer-specific accumulation of PFOS from diSPAP and will be helpful to track indirect sources of PFOS in the future.

}, keywords = {Alkanesulfonic Acids, Animals, Biotransformation, Chromatography, High Pressure Liquid, Environmental Monitoring, Esters, Fluorocarbons, Gas Chromatography-Mass Spectrometry, Half-Life, Hydrocarbons, Fluorinated, Isomerism, Kinetics, Metabolic Networks and Pathways, Organophosphorus Compounds, Oryzias, Phosphates, Reference Standards, Sulfonamides}, issn = {1520-5851}, doi = {10.1021/es404867w}, author = {Peng, Hui and Zhang, Shiyi and Sun, Jianxian and Zhang, Zhong and Giesy, John P and Hu, Jianying} } @article {111, title = {Trophic transfer of dechloranes in the marine food web of Liaodong Bay, north China.}, journal = {Environ Sci Technol}, volume = {48}, year = {2014}, month = {2014 May 20}, pages = {5458-66}, abstract = {

Dechloranes are of particular concern because of their ubiquity in environmental matrices, but little is known about their trophic transfer in aquatic food web. This study investigated the trophic transfer of seven dechloranes in a marine food web from Liaodong Bay, China. Dechloranes were determined in sediments and 15 marine species including benthic invertebrates, fish and gulls collected from Liaodong Bay. Biomagnification factors (BMFTL) of dechloranes in black-headed gulls were calculated to be 6.4, 1.7, 0.45, 0.36, 0.14, and 0.11 for mirex, Dechlorane 602 (Dec 602), Dechlorane 603 (Dec 603), antiundecachloropentacyclooctadecadiene (anti-Cl11DP), syn-dechlorane plus (syn-DP), and anti-DP. Significantly positive relationships were found between lipid equivalent concentrations of mirex, Dec 602, and anti-Cl11DP and trophic levels, and the trophic magnification factors (TMFs) were 13, 3.7, and 5.6, respectively, indicating that these compounds undergo trophic magnification in the aquatic food web. Lipid equivalent concentrations of Dec 603 and DP isomers did not exhibit a statistically significant correlation with trophic levels. The relatively low trophic magnification potentials of Dec 603 and DP isomers were possibly due to their extreme hydrophobicity (logKOW: 11.2-11.3) and subsequent low bioavailabilities compared with mirex (7.0), Dec 602 (8.1) and anti-Cl11DP. The results provided important information for understanding the ecological risk of dechloranes.

}, keywords = {Animals, Aquatic Organisms, Bays, Charadriiformes, China, Environmental Monitoring, Fishes, Food Chain, Geologic Sediments, Hydrocarbons, Chlorinated, Invertebrates, Ontario, Regression Analysis, Water Pollutants, Chemical}, issn = {1520-5851}, doi = {10.1021/es500229y}, author = {Peng, Hui and Wan, Yi and Zhang, Kun and Sun, Jianxian and Hu, Jianying} } @article {121, title = {Molecular and physiological characterization of fluoroquinolone resistance in relation to uropathogenicity among Escherichia coli isolates isolated from Wenyu River, China.}, journal = {Chemosphere}, volume = {87}, year = {2012}, month = {2012 Mar}, pages = {37-42}, abstract = {

Increasing antibacterial resistance and pathogenicity in the environment is of growing concern due to its potential human risk. In the present study, 236 Escherichia coli isolates were collected from Wenyu River in China on drugless (48 isolates) and quinolone-containing plates (189 isolates). Their minimum inhibitory concentrations (MICs) were determined ranging from 0.125 μg mL(-1) to 128 μg mL(-1). Mutation points related to fluoroquinolone resistance were observed at S83 to L and D87 to N or Y in the GyrA subunit and S80 to R or I and E84 to G in the ParC subunit. Generally, MICs of LEV and GAT are dependent on the patterns of these mutation points. The profile with three mutation points was related to LEV-resistant E. coli isolates, and the (S83L, D87N+S80I) mutation profile was most prevalent (65.7\%) in LEV-resistant isolates, while a large proportion of isolates, even those with three mutation points, were susceptive to GAT. The incidence of virulence factors in LEV-resistant isolates (44.7\%, 59/132) was much higher than in nonresistant isolates (23.1\%, 24/104) (χ(2)=11.925, 1{\textdegree} of freedom, p\<0.001) indicating that fluoroquinolone-resistant E. coli would pose a potential risk. A similar distribution was also found in isolates resistant to GAT (χ(2)=7.843, 1{\textdegree} of freedom, p=0.0079).

}, keywords = {Anti-Bacterial Agents, China, Drug Resistance, Bacterial, Escherichia coli, Fluoroquinolones, Rivers, Water Pollutants, Chemical}, issn = {1879-1298}, doi = {10.1016/j.chemosphere.2011.11.050}, author = {Sun, Jianxian and Hu, Jianying and Peng, Hui and Shi, Jiachen and Dong, Zhaomin} }