Cold-Source Composite Welding Repair of 9Cr2Mo Thick-Walled Parts: Microstructure, Mechanical Properties, and Finite Element Simulation.

The restoration of large support rollers poses an industrial challenge due to the high energy consumption of traditional repair methods. Consequently, a novel approach for repairing support rollers has been introduced and tested on thick-walled components. Finite element simulations aided the study of welding repairs for large thick-walled components, examining element distribution, microstructure, mechanical properties, and residual stress distribution across various processes. The results indicate that employing ABAQUS2023 finite element software to analyze stress variations under different working conditions, the Dynamically Controlled Low-Stress No-Distortion method effectively mitigates residual stresses both during and post welding, reducing average transverse residual stresses by 14.5% and average longitudinal residual stresses in the weld zone by 29.1%. The Dynamically Controlled Low-Stress No-Distortion method narrows the high-temperature range of the heat source, consequently decreasing the size of the heat-affected zone by 33.3% compared to conventional welding. The microstructure featured dendrites and equiaxed columnar crystals, with the Dynamically Controlled Low-Stress No-Distortion method capable of grain refinement, transforming some equiaxed columnar crystals into cellular structures. As grains were refined, microhardness improved, with the covering layer's microhardness rising by 14.68%. A comparison between simulated and measured values of lateral and longitudinal residual stresses at corresponding points revealed discrepancies of 14.6% and 20.5% in accuracy, respectively.

Noninvasive skin swab analysis detects environmental drug exposure of pharmacy staff.

The skin is complex with multiple layers serving protective, regulatory, and detective functions. The skin hosts chemicals originating from consumption, synthesis, and the environment. Skin chemicals can provide insight into one's daily routine or their level of safety in a work environment. The goal of this study was to investigate the utility of noninvasive skin swabs to detect drugs in a pharmacy setting and to determine whether drugs are transferred to the skin of pharmacy staff. To answer this question, skin swabs were collected from healthy pharmacy staff workers and healthy non-pharmacy individuals and analyzed via untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS). Drugs were annotated through library matching against the GNPS community spectral library. We then used questionnaire data to exclude medications that participants took orally or applied topically and focused on the drugs participants were exposed to in the work setting. Overall, pharmacy staff had a higher number and variety of medications on their skin as compared with healthy individuals who did not work in a pharmacy. In addition, we identified some chemicals such as N,N-Diethyl-metatoluamide on a large number of subjects in both experimental and control groups, indicating environmental exposure to this compound may be ubiquitous and long-lasting.

IL-22 resolves MASLD via enterocyte STAT3 restoration of diet-perturbed intestinal homeostasis.

The exponential rise in metabolic dysfunction-associated steatotic liver disease (MASLD) parallels the ever-increasing consumption of energy-dense diets, underscoring the need for effective MASLD-resolving drugs. MASLD pathogenesis is linked to obesity, diabetes, "gut-liver axis" alterations, and defective interleukin-22 (IL-22) signaling. Although barrier-protective IL-22 blunts diet-induced metabolic alterations, inhibits lipid intake, and reverses microbial dysbiosis, obesogenic diets rapidly suppress its production by small intestine-localized innate lymphocytes. This results in STAT3 inhibition in intestinal epithelial cells (IECs) and expansion of the absorptive enterocyte compartment. These MASLD-sustaining aberrations were reversed by administration of recombinant IL-22, which resolved hepatosteatosis, inflammation, fibrosis, and insulin resistance. Exogenous IL-22 exerted its therapeutic effects through its IEC receptor, rather than hepatocytes, activating STAT3 and inhibiting WNT-ß-catenin signaling to shrink the absorptive enterocyte compartment. By reversing diet-reinforced macronutrient absorption, the main source of liver lipids, IL-22 signaling restoration represents a potentially effective interception of dietary obesity and MASLD.

Epigenetic Regulation of RNF135 by LSD1 Promotes Stemness Maintenance and Brain Metastasis in Lung Adenocarcinoma.

RING finger protein 135 (RNF135) is identified as a regulator in certain cancer types. However, its role and molecular mechanisms in lung adenocarcinoma (LUAD) are still unclear. Herein, we investigated the level of RNF135 in tumor tissues of LUAD patients using the UALCAN database and confirmed the data by real-time PCR and western blot analysis. The effects of RNF135 on stemness maintenance and migration/invasion capability of LUAD cells were investigated by sphere formation, flow cytometry, wound healing, and transwell assay. Limiting dilution xenograft assay and intracardiac injection of LUAD cells were applied to assess the implications of RNF135 in tumorigenesis and brain metastasis. Our results revealed that RNF135 was upregulated in tumor tissues of LUAD patients and was positively correlated with poor prognosis. Knockdown of RNF135 suppressed cancer stem cells (CSCs)-like properties, and migration/invasion capability of A549 and NCI-H1975 cells. Conversely, overexpression of RNF135 augmented CSCs-like traits and migration/invasion ability of LUAD cells. Limiting dilution xenograft assay demonstrated that RNF135 was required for the self-renewal of CSCs to initiate LUAD development. Overexpression of RNF135 in A549 cells increased their ability to metastasize to the brain in vivo. Mechanistically, the transcriptional activation of RNF135 by LSD1 involved H3K9me2 demethylation at the promoter region of RNF135. Reexpression of RNF135 in LSD1-silenced A549 cells was able to reverse LSD1-mediated stemness maintenance and migration/invasion capability. Overall, our results implied that targeting of LSD1/RNF135 axis might be a feasible method to suppress tumorigenesis and brain metastasis of LUAD patients.

plantMASST - Community-driven chemotaxonomic digitization of plants.

Understanding the distribution of hundreds of thousands of plant metabolites across the plant kingdom presents a challenge. To address this, we curated publicly available LC-MS/MS data from 19,075 plant extracts and developed the plantMASST reference database encompassing 246 botanical families, 1,469 genera, and 2,793 species. This taxonomically focused database facilitates the exploration of plant-derived molecules using tandem mass spectrometry (MS/MS) spectra. This tool will aid in drug discovery, biosynthesis, (chemo)taxonomy, and the evolutionary ecology of herbivore interactions.

Co-occurrence network analysis reveals the alterations of the skin microbiome and metabolome in adults with mild to moderate atopic dermatitis.

Skin microbiome can be altered in patients with atopic dermatitis (AD). An understanding of the changes from healthy to atopic skin can help develop new targets for treatment by identifying microbial and molecular biomarkers. This study investigates the skin microbiome and metabolome of healthy adult subjects and lesion (ADL) and non-lesion (ADNL) of AD patients by 16S rRNA gene sequencing and mass spectrometry, respectively. Samples from AD patients showed alterations in the diversity and composition of the skin microbiome, with ADL skin having the greatest divergence. Staphylococcus species, especially S. aureus, were significantly increased in AD patients. Metabolomic profiles were also different between the groups. Dipeptide derivatives are more abundant in ADL, which may be related to skin inflammation. Co-occurrence network analysis of the microbiome and metabolomics data revealed higher co-occurrence of metabolites and bacteria in healthy ADNL compared to ADL. S. aureus co-occurred with dipeptide derivatives in ADL, while phytosphingosine-derived compounds showed co-occurrences with commensal bacteria, for example, Paracoccus sp., Pseudomonas sp., Prevotella bivia, Lactobacillus iners, Anaerococcus sp., Micrococcus sp., Corynebacterium ureicelerivorans, Corynebacterium massiliense, Streptococcus thermophilus, and Roseomonas mucosa, in healthy and ADNL groups. Therefore, these findings provide valuable insights into how AD affects the human skin metabolome and microbiome.IMPORTANCEThis study provides valuable insight into changes in the skin microbiome and associated metabolomic profiles in an adult population with mild to moderate atopic dermatitis. It also identifies new therapeutic targets that may be useful for developing personalized treatments for individuals with atopic dermatitis based on their unique skin microbiome and metabolic profiles.

A Noise-Induced Hearing Loss Prediction Model Based on Asymmetric Convolution for Workers Exposed to Complex Industrial Noise.

OBJECTIVES: Current approaches for evaluating noise-induced hearing loss (NIHL), such as the International Standards Organization 1999 (ISO) 1999 prediction model, rely mainly on noise energy and exposure time, thus ignoring the intricate time-frequency characteristics of noise, which also play an important role in NIHL evaluation. In this study, an innovative NIHL prediction model based on temporal and spectral feature extraction using an asymmetric convolution algorithm is proposed. DESIGN: Personal data and individual occupational noise records from 2214 workers across 23 factories in Zhejiang Province, China, were used in this study. In addition to traditional metrics like noise energy and exposure duration, the importance of time-frequency features in NIHL assessment was also emphasized. To capture these features, operations such as random sampling, windowing, short-time Fourier transform, and splicing were performed to create time-frequency spectrograms from noise recordings. Two asymmetric convolution kernels then were used to extract these critical features. These features, combined with personal information (e.g., age, length of service) in various configurations, were used as model inputs. The optimal network structure was selected based on the area under the curve (AUC) from 10-fold cross-validation, alongside the Wilcoxon signed ranks test. The proposed model was compared with the support vector machine (SVM) and ISO 1999 models, and the superiority of the new approach was verified by ablation experiments. RESULTS: The proposed model had an AUC of 0.7768 ± 0.0223 (mean ± SD), outperforming both the SVM model (AUC: 0.7504 ± 0.0273) and the ISO 1999 model (AUC: 0.5094 ± 0.0071). Wilcoxon signed ranks tests confirmed the significant improvement of the proposed model ( p = 0.0025 compared with ISO 1999, and p = 0.00142 compared with SVM). CONCLUSIONS: This study introduced a new NIHL prediction method that provides deeper insights into industrial noise exposure data. The results demonstrated the superior performance of the new model over ISO 1999 and SVM models. By combining time-frequency features and personal information, the proposed approach bridged the gap between conventional noise assessment and machine learning-based methods, effectively improving the ability to protect workers' hearing.

High-Purity Generation and Switching of Twisted Single Photons.

Quantum technologies, if scaled into a high-dimensional Hilbert space, can dramatically enhance connection capabilities with supporting higher bit rates and ultrasecure information transfer. Twisted single photons, carrying orbital angular momentum (OAM) as an unbounded dimension, could address the growing demand for high-dimensional quantum information encoding and transmission. By hybrid integration of two-dimensional semiconductor WSe_{2} with a spin-orbit-coupled microring resonator, we demonstrate an integrated tunable twisted single photon source with the ability to precisely define and switch between highly pure spin-OAM states. Our results feature a single photon purity of g^{(2)}(0)∼0.13 with a cavity-enhanced quantum yield of 76% and a high OAM mode purity up to 96.9%. Moreover, the demonstrated quantum-chiral control can also enable new quantum functionality such as single photon routing for efficient quantum information processing on chip.

Ex vivo study of molecular changes of stained teeth following hydrogen peroxide and peroxymonosulfate treatments.

White teeth can give confidence and tend to be associated with a healthier lifestyle in modern society. Therefore, tooth-bleaching strategies have been developed, including the use of hydrogen peroxide. Recently, peroxymonosulfate has been introduced as an alternative bleaching method to hydrogen peroxide. Although both chemicals are oxidizing agents, their effects on the molecular composition of the stained teeth are yet unknown. In this study, the molecular profiles of teeth bleached with hydrogen peroxide and peroxymonosulfate were compared using Liquid Chromatography-Tandem Mass Spectrometry. Statistical analyses were used to assess the samples. In addition, reference spectral libraries and in silico tools were used to perform metabolite annotation. Overall, principal component analysis showed a strong separation between control and hydrogen peroxide and peroxymonosulfate samples (p < 0.001). The analysis of molecular changes revealed amino acids and dipeptides in stained teeth samples after hydrogen peroxide and peroxymonosulfate treatments. Noteworthy, the two bleaching methods led to distinct molecular profiles. For example, diterpenoids were more prevalent after peroxymonosulfate treatment, while a greater abundance of alkaloids was detected after hydrogen peroxide treatment. Whereas non-bleached samples (controls) showed mainly lipids. Therefore, this study shows how two different tooth-whitening peroxides could affect the molecular profiles of human teeth.

Urine Excretion, Organ Distribution, and Placental Transfer of 6PPD and 6PPD-Quinone in Mice and Potential Developmental Toxicity through Nuclear Receptor Pathways.

The rubber antioxidant 6PPD has gained significant attention due to its highly toxic transformation product, 6PPD-quinone (6PPDQ). Despite their detection in urines of pregnant women, the placental transfer and developmental toxicity of 6PPD and 6PPDQ are unknown. Here, we treated C57Bl/6 mice with 4 mg/kg 6PPD or 6PPDQ to investigate their urine excretion and placental transfer. Female and male mice exhibited sex difference in excretion profiles of 6PPD and 6PPDQ. Urine concentrations of 6PPDQ were one order of magnitude lower than those of 6PPD, suggesting lower excretion and higher bioaccumulation of 6PPDQ. In pregnant mice treated with 6PPD or 6PPDQ from embryonic day 11.5 to 15.5, 6PPDQ showed ∼1.5-8 times higher concentrations than 6PPD in placenta, embryo body, and embryo brain, suggesting higher placental transfer of 6PPDQ. Using in vitro dual-luciferase reporter assays, we revealed that 6PPDQ activated the human retinoic acid receptor α (RARα) and retinoid X receptor α (RXRα) at concentrations as low as 0.3 µM, which was ∼10-fold higher than the concentrations detected in human urines. 6PPD activated the RXRα at concentrations as low as 1.2 µM. These results demonstrate the exposure risks of 6PPD and 6PPDQ during pregnancy and emphasize the need for further toxicological and epidemiological investigations.

Topological quadratic-node semimetal in a photonic microring lattice.

Graphene, with its two linearly dispersing Dirac points with opposite windings, is the minimal topological nodal configuration in the hexagonal Brillouin zone. Topological semimetals with higher-order nodes beyond the Dirac points have recently attracted considerable interest due to their rich chiral physics and their potential for the design of next-generation integrated devices. Here we report the experimental realization of the topological semimetal with quadratic nodes in a photonic microring lattice. Our structure hosts a robust second-order node at the center of the Brillouin zone and two Dirac points at the Brillouin zone boundary-the second minimal configuration, next to graphene, that satisfies the Nielsen-Ninomiya theorem. The symmetry-protected quadratic nodal point, together with the Dirac points, leads to the coexistence of massive and massless components in a hybrid chiral particle. This gives rise to unique transport properties, which we demonstrate by directly imaging simultaneous Klein and anti-Klein tunnelling in the microring lattice.

Chemical characteristics, leaching, and stability of the ubiquitous tire rubber-derived toxicant 6PPD-quinone.

We here report chemical characteristics relevant to the fate and transport of the recently discovered environmental toxicant 6PPD-quinone (2-((4-methylpentan-2-yl)amino)-5-(phenylamino)cyclohexa-2,5-diene-1,4-dione or "6PPDQ"). 6PPDQ is a transformation product of the tire rubber antioxidant 6PPD that is ubiquitous in roadway environments, including atmospheric particulate matter, soils, runoff, and receiving waters, after dispersal from tire rubber use and wear on roadways. The aqueous solubility and octanol-water partitioning coefficient (i.e. log KOW) for 6PPDQ were measured to be 38 ± 10 µg L-1 and 4.30 ± 0.02, respectively. Within the context of analytical measurement and laboratory processing, sorption to various laboratory materials was evaluated, indicating that glass was largely inert but loss of 6PPDQ to other materials was common. Aqueous leaching simulations from tire tread wear particles (TWPs) indicated short term release of ∼5.2 µg 6PPDQ per gram TWP over 6 h under flow-through conditions. Aqueous stability tests observed a slight-to-moderate loss of 6PPDQ over 47 days (26 ± 3% loss) for pH 5, 7 and 9. These measured physicochemical properties suggest that 6PPDQ is generally poorly soluble but fairly stable over short time periods in simple aqueous systems. 6PPDQ can also leach readily from TWPs for subsequent environmental transport, posing high potential for adverse effects in local aquatic environments.

Transformation Products of Tire Rubber Antioxidant 6PPD in Heterogeneous Gas-Phase Ozonation: Identification and Environmental Occurrence.

6PPD, a tire rubber antioxidant, poses substantial ecological risks because it can form a highly toxic quinone transformation product (TP), 6PPD-quinone (6PPDQ), during exposure to gas-phase ozone. Important data gaps exist regarding the structures, reaction mechanisms, and environmental occurrence of TPs from 6PPD ozonation. To address these data gaps, gas-phase ozonation of 6PPD was conducted over 24-168 h and ozonation TPs were characterized using high-resolution mass spectrometry. The probable structures were proposed for 23 TPs with 5 subsequently standard-verified. Consistent with prior findings, 6PPDQ (C18H22N2O2) was one of the major TPs in 6PPD ozonation (∼1 to 19% yield). Notably, 6PPDQ was not observed during ozonation of 6QDI (N-(1,3-dimethylbutyl)-N'-phenyl-p-quinonediimine), indicating that 6PPDQ formation does not proceed through 6QDI or associated 6QDI TPs. Other major 6PPD TPs included multiple C18H22N2O and C18H22N2O2 isomers, with presumptive N-oxide, N,N'-dioxide, and orthoquinone structures. Standard-verified TPs were quantified in roadway-impacted environmental samples, with total concentrations of 130 ± 3.2 µg/g in methanol extracts of tire tread wear particles (TWPs), 34 ± 4 µg/g-TWP in aqueous TWP leachates, 2700 ± 1500 ng/L in roadway runoff, and 1900 ± 1200 ng/L in roadway-impacted creeks. These data demonstrate that 6PPD TPs are likely an important and ubiquitous class of contaminants in roadway-impacted environments.

Screening p-Phenylenediamine Antioxidants, Their Transformation Products, and Industrial Chemical Additives in Crumb Rubber and Elastomeric Consumer Products.

Recently, roadway releases of N,N'-substituted p-phenylenediamine (PPD) antioxidants and their transformation products (TPs) received significant attention due to the highly toxic 6PPD-quinone. However, the occurrence of PPDs and TPs in recycled tire rubber products remains uncharacterized. Here, we analyzed tire wear particles (TWPs), recycled rubber doormats, and turf-field crumb rubbers for seven PPD antioxidants, five PPD-quinones (PPDQs), and five other 6PPD TPs using liquid chromatography-tandem mass spectrometry. PPD antioxidants, PPDQs, and other TPs were present in all samples with chemical profiles dominated by 6PPD, DTPD, DPPD, and their corresponding PPDQs. Interestingly, the individual [PPDQ]/[PPD] and [TP]/[PPD] ratios significantly increased as total concentrations of the PPD-derived chemical decreased, indicating that TPs (including PPDQs) dominated the PPD-derived compounds with increased environmental weathering. Furthermore, we quantified 15 other industrial rubber additives (including bonding agents, vulcanization accelerators, benzotriazole and benzothiazole derivatives, and diphenylamine antioxidants), observing that PPD-derived chemical concentrations were 0.5-6 times higher than these often-studied additives. We also screened various other elastomeric consumer products, consistently detecting PPD-derived compounds in lab stoppers, sneaker soles, and rubber garden hose samples. These data emphasize that PPD antioxidants, PPDQs, and related TPs are important, previously overlooked contaminant classes in tire rubbers and elastomeric consumer products.

Spin-orbit microlaser emitting in a four-dimensional Hilbert space.

A step towards the next generation of high-capacity, noise-resilient communication and computing technologies is a substantial increase in the dimensionality of information space and the synthesis of superposition states on an N-dimensional (N > 2) Hilbert space featuring exotic group symmetries. Despite the rapid development of photonic devices and systems, on-chip information technologies are mostly limited to two-level systems owing to the lack of sufficient reconfigurability to satisfy the stringent requirement for 2(N - 1) degrees of freedom, intrinsically associated with the increase of synthetic dimensionalities. Even with extensive efforts dedicated to recently emerged vector lasers and microcavities for the expansion of dimensionalities1-10, it still remains a challenge to actively tune the diversified, high-dimensional superposition states of light on demand. Here we demonstrate a hyperdimensional, spin-orbit microlaser for chip-scale flexible generation and manipulation of arbitrary four-level states. Two microcavities coupled through a non-Hermitian synthetic gauge field are designed to emit spin-orbit-coupled states of light with six degrees of freedom. The vectorial state of the emitted laser beam in free space can be mapped on a Bloch hypersphere defining an SU(4) symmetry, demonstrating dynamical generation and reconfiguration of high-dimensional superposition states with high fidelity.

Biotransformation of Current-Use Progestin Dienogest and Drospirenone in Laboratory-Scale Activated Sludge Systems Forms High-Yield Products with Altered Endocrine Activity.

Dienogest (DIE) and drospirenone (DRO) are two fourth-generation synthetic progestins widely used as oral contraceptives. Despite their increasing detection in wastewaters and surface waters, their fate during biological wastewater treatment is unclear. Here, we investigated DIE and DRO biotransformation with representative activated sludge batch incubations and identified relevant transformation products (TPs) using high-resolution mass spectrometry. DIE exhibited slow biotransformation (16-30 h half-life) and proceeded through a quantitative aromatic dehydrogenation to form TP 309 (molar yields of ∼55%), an aromatic TP ∼30% estrogenic as 17ß-estradiol. DRO experienced more rapid biotransformation (<0.5 h half-life), and 1,2-dehydrogenation formed the major TP 364 (molar yields of ∼40%), an antimineralocorticoid drug candidate named as spirorenone. Lactone ring hydrolysis was another important biotransformation pathway for DRO (molar yields of ∼20%) and generated pharmacologically inactive TP 384. Other minor pathways for DIE and DRO included hydroxylation, methoxylation, and 3-keto and C4(5) double-bond hydrogenation; distinct bioactivities are plausible for such TPs, including antigestagenic activity, antigonadotropic activity, and pregnancy inhibition effects. Thus, biotransformation products of DIE and DRO during wastewater treatment should be considered in environmental assessments of synthetic progestins, especially certain TPs such as the estrogenic TP 309 of DIE and the antimineralocorticoid spirorenone (TP 364) of DRO.

CHN1 promotes epithelial-mesenchymal transition via the Akt/GSK-3ß/Snail pathway in cervical carcinoma.

BACKGROUND: Metastasis and invasion are crucial in determining the mortality of cervical carcinoma (CC) patients. The epithelial-mesenchymal transition (EMT) is now a universal explanation for the mechanisms of tumor metastasis. Α-chimeric protein (α-chimaerin, CHN1) plays an important role in the regulation of signal transduction and development. However, the molecular regulatory relationships between CHN1 and CC progression in relation to EMT have not yet been identified. METHODS: The expression of CHN1 in CC tissues, adjacent tissues, and lymph node metastases from CC patients was detected by immunohistochemistry. Upregulation and knockdown of CHN1 were achieved by transfection of CC cells. The effect of CHN1 on cell proliferation was determined by CCK-8 and plate clone formation assays. Changes in migration and invasion capabilities were evaluated using scratch migration and transwell invasion assays. The effect of CHN1 overexpression and interference on xenograft tumor growth was determined by tumor weight and pathological analyses. The expression of EMT-related mRNAs was measured by qRT-PCR in transfected CC cells. EMT-related proteins and Akt/GSK-3ß/Snail signaling pathway-related proteins were also evaluated by western blotting. RESULTS: CHN1 was overexpressed in CC tissues and was associated with lymph node metastasis and low survival in CC patients. Overexpression of CHN1 promoted cell proliferation, migration, and invasion in CC cells. In contrast, silencing of CHN1 inhibited these phenomena. Overexpression of CHN1 promoted tumor formation in an in vivo xenograft tumor mouse model, with increased tumor volumes and weights. In addition, CHN1 induced the expression of EMT-related transcription factors, accompanied by the decreased expression of epithelial markers and increased expression of mesenchymal markers. The Akt/GSK-3ß/Snail signaling pathway was activated by overexpression of CHN1 in vitro, and activation of this pathway was inhibited by the signaling pathway inhibitor LY294002. CONCLUSION: These results suggest that CHN1 promotes the development and progression of cervical carcinoma via the Akt/GSK-3ß/Snail pathway by inducing EMT.

Higher-dimensional supersymmetric microlaser arrays.

The nonlinear scaling of complexity with the increased number of components in integrated photonics is a major obstacle impeding large-scale, phase-locked laser arrays. Here, we develop a higher-dimensional supersymmetry formalism for precise mode control and nonlinear power scaling. Our supersymmetric microlaser arrays feature phase-locked coherence and synchronization of all of the evanescently coupled microring lasers-collectively oscillating in the fundamental transverse supermode-which enables high-radiance, small-divergence, and single-frequency laser emission with a two-orders-of-magnitude enhancement in energy density. We also demonstrate the feasibility of structuring high-radiance vortex laser beams, which enhance the laser performance by taking full advantage of spatial degrees of freedom of light. Our approach provides a route for designing large-scale integrated photonic systems in both classical and quantum regimes.

Toxicity Testing of Effluent-Dominated Stream Using Predictive Molecular-Level Toxicity Signatures Based on High-Resolution Mass Spectrometry: A Case Study of the Lubbock Canyon Lake System.

Current aquatic toxicity assessments usually focus on targeted analyses coupled with toxicity testing to determine the impacts of complex mixtures on aquatic organisms. However, based on this approach alone, it is sometimes difficult to explain observed toxicity from the selected chemical analytes. Recent analytical advances such as high-resolution mass spectrometry (HRMS) can improve the characterizations of the chemical composition of complex mixtures, but the intensive labor required to produce confident identifications limits its utility in high-throughput screening. In the present study, we evaluated a rapid workflow to predict potential toxicity signatures of complex water samples based on high-throughput, tentative HRMS identifications derived from database matching, followed by identification of chemical-ligand interactions and pathway identification. We tested the workflow with water samples from the effluent-dominated Lubbock Canyon Lake System (LCLS). Results across all sites showed that predicted toxicity signatures had little variation when correcting for HRMS false-positive rates. The most common pathways across sites were gonadotropin-releasing hormone receptor and α-adrenergic receptor signaling. Alterations to the predicted pathways were successfully observed in larval zebrafish exposures to LCLS water samples. These results may allow researchers to better utilize rapid assessments of HRMS data for the assessment of adverse impacts on aquatic organisms.