@article {287, title = {An abundant ginger compound furanodienone alleviates gut inflammation via the xenobiotic nuclear receptor PXR in mice.}, journal = {Nat Commun}, volume = {16}, year = {2025}, month = {2025 Feb 03}, pages = {1280}, abstract = {

The literature documenting the value of drug-like molecules found in natural products is vast. Although many dietary and herbal remedies have been found to be effective for treating intestinal inflammation, the identification of their active components has lagged behind. In this study, we find that a major ginger component, furanodienone (FDN), is a selective pregnane X receptor (PXR) ligand with agonistic transcriptional outcomes. We show that FDN binds within a sub-pocket of the PXR ligand binding domain (LBD), with subsequent alterations in LBD structure. Using male mice, we show that orally provided FDN has potent PXR-dependant anti-inflammatory outcomes that are colon-specific. Increased affinity and target gene activation in the presence of synergistically acting agonists indicates further opportunities for augmenting FDN activity, efficacy and safety. Collectively, these results support the translational potential of FDN as a therapeutic agent for the treatment and prevention of colonic diseases.

}, keywords = {Animals, Anti-Inflammatory Agents, Colitis, Colon, Furans, Humans, Inflammation, Ligands, Male, Mice, Mice, Inbred C57BL, Pregnane X Receptor, Zingiber officinale}, issn = {2041-1723}, doi = {10.1038/s41467-025-56624-0}, author = {Wang, Xiaojuan and Zhang, Guohui and Bian, Zhiwei and Chow, Vimanda and Grimaldi, Marina and Carivenc, Coralie and Sirounian, Savannah and Li, Hao and Sladekova, Lucia and Mott, Stefano and Luperi, Yulia and Gong, Yufeng and Costello, Cait and Li, Linhao and Jachimowicz, Matthew and Guo, Miao and Hu, Shian and Wilson, Derek and Balaguer, Patrick and Bourguet, William and Mani, Sridhar and Bonati, Laura and Peng, Hui and March, John and Wang, Hongbing and Wang, Shengpeng and Krause, Henry M and Liu, Jiabao} } @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 {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 {273, title = {Hydroxyl radical oxidation of chemical contaminants on indoor surfaces and dust.}, journal = {Proc Natl Acad Sci U S A}, volume = {121}, year = {2024}, month = {2024 Nov 05}, pages = {e2414762121}, abstract = {

Humans are widely exposed to semivolatile organic contaminants in indoor environments. Many contaminants have long lifetimes following partitioning to the large surface reservoirs present indoors, which leads to long exposure times to gas-phase oxidants and multiphase chemistry. Studies have shown selective multiphase oxidation of organics on indoor surfaces, but the presence of hydroxyl radicals with nonselective reactivity and evidence of multiphase OH radical reactivity toward common indoor contaminants indicates that there may be additional unknown transformation chemistry indoors. We screened genuine indoor samples for 60 OH radical oxidation products of the common plasticizer and endocrine-disrupting contaminant bis(2-ethylhexyl) phthalate (DEHP) identified in laboratory experiments using nontargeted high-resolution mass spectrometry. At least 30 and 10 of these products are observed in indoor dust and DEHP films exposed to ambient indoor conditions, respectively, indicating that multiphase OH reactions occur indoors. Using the PROTEX model and a multimedia indoor chemical fate model, we demonstrate that these products have long indoor lifetimes and cause a higher potential for human exposure than DEHP. Some of these products are more active endocrine disruptors than DEHP itself, but most have unknown toxicities. Coexposure to all oxidation products will likely have an additive effect, leading to higher human health risks from indoor organic contaminants than previously thought. Due to the nonselective reactivity of OH radicals, it is likely that most indoor contaminants follow similar chemistry, and further study is needed to understand the prevalence and human health implications of such multiphase chemistry.

}, issn = {1091-6490}, doi = {10.1073/pnas.2414762121}, author = {Fahy, William D and Gong, Yufeng and Wang, Shenghong and Zhang, Zhizhen and Li, Li and Peng, Hui and Abbatt, Jonathan P D} } @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 {260, title = {Light Exposure of Wood Smoke Aerosol: Connecting Optical Properties, Oxidation, Radical Formation, and Chemical Composition}, journal = {ACS ES\&T Air}, volume = {1}, year = {2024}, author = {Liu-Kang, Carolyn and Sokolova, Anna and Gong, Yufeng and Fahy, William D and Peng, Hui and Abbatt, Jonathan PD} } @article {254, title = {Multiphase Ozonolysis of Bisphenol A: Chemical Transformations on Surfaces in the Environment.}, journal = {Environ Sci Technol}, year = {2024}, month = {2024 Feb 13}, abstract = {

High global plastic production volumes have led to the widespread presence of bisphenol compounds in human living and working environments. The most common bisphenol, bisphenol A (BPA), despite being endocrine disruptive and estrogenic, is still not fully banned worldwide, leading to continued human exposure via particles in air, dust, and surfaces in both outdoor and indoor environments. While its abundance is well documented, few studies have addressed the chemical transformations of BPA, the properties of its reactive products, and their toxicity. Here, the first gas-surface multiphase ozonolysis experiment of BPA thin films, at a constant ozone mixing ratio of 100 ppb, was performed in a flow tube for periods up to 24 h. Three transformation products involving the addition of 1, 2, and 3 oxygen atoms to the molecule were identified by LC-ESI-HRMS analyses. Exposure of indoor air to thin BPA surface films and BPA-containing thermal paper over periods of days validated the flow tube experiments, demonstrating the rapid nature of this multiphase ozonolysis reaction at atmospherically relevant ozone levels. Multiple transformation pathways are proposed that are likely applicable to not only BPA but also emerging commercial bisphenol products.

}, issn = {1520-5851}, doi = {10.1021/acs.est.3c08932}, author = {Yu, Jie and Gong, Yufeng and Nair, Pranav and Liggio, John and Peng, Hui* and Abbatt, Jonathan P D*} } @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 {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} }