Journal of Hazardous Materials

Understanding the toxicity of hazardous metals in microalgae is critical for environmental risk assessment and sustainable phycoremediation. Metal-tolerant organisms provide powerful models for dissecting the mechanisms that mitigate metal toxicity. Here, we investigated the cellular and molecular responses to uranium (U) chemotoxicity in the metal-tolerant microalga Coelastrella sp. PCV. We used an integrated multi-omics and high-resolution imaging approach, combined with physiological analyses, to elucidate the mechanisms underlying U tolerance in Coelastrella. Using TEM-EDX, U was localized to the cell wall, polyphosphate bodies within acidocalcisomes, and vacuoles. Three-dimensional cell reconstruction and morphometric analysis using FIB-SEM showed that U-challenged cells displayed increased vacuolization, reflecting sequestration of uranyl ions and autophagy-mediated detoxification. Transcriptome responses were rapid and extensive, characterized by repression of cell division and photosynthesis, and pronounced imbalance in protein turnover and trafficking. Uranium also disrupted the homeostasis of essential elements, with marked rewiring of gene networks governing molybdenum, manganese, phosphate, iron and calcium homeostasis, notably affecting transporters and metal-binding proteins. Coelastrella sp. PCV efficiently sequestered U in acidocalcisomes and vacuoles, while rapidly excluding U from the cell. These coordinated detoxification responses are likely mediated by calcium, iron, ABC, and MATE transporters among the strongly deregulated genes under U stress.

Chlorinated per- and polyfluoroalkyl substances (Cl-PFAS) represent an important subgroup in replacement chemicals for legacy PFAS, and they have been detected in various environments including water bodies, soil, as well as air particles. However, the biodegradability of these chemicals is largely unknown. A recent study reported dechlorination triggered anaerobic biodefluorination of Cl-PFCAs by activated sludge communities. In this study, we further investigated the biodefluorination of Cl-PFCAs by pure cultures. Six of ten selected Cl-PFCAs displayed significant defluorination by Acetobacterium bakii, and corresponding pathways were proposed according to transformation product analysis. Several additional Acetobacterium species were all capable of defluorinating 3,5,7,8-tetrachloro-2,2,3,4,4,5,6,6,7,8,8- undecafluorooctanoic acid (CTFE4) with >50% removal of organic fluorine. On the contrary, Clostridium homopropionicum cannot defluorinate CTFE4. Crude protein extraction experiment showed that the enzymes responsible for CTFE4 dechlorination and defluorination required anaerobic atmosphere to function. Differential gene expression was analyzed according to RNA sequencing analysis, and the results indicated vitamin B12 related enzymes may involve in CTFE4 dechlorination.

Poorly soluble lanthanide minerals pose challenges for both a sustainable extraction of lanthanides as key resources for decarbonization and lanthanide-dependent microbial metabolism. Microbial use of lanthanides is widespread, yet bacterias preference for light lanthanides requires differentiation mechanisms that enable downstream utilization. Whether lanthanide discrimination occurs during access, mobilization, uptake, or intracellular processing is mostly unknown and likely controlled by habitat and bioavailability. We studied microbial lanthanide mobilization and uptake from different lanthanide minerals, an alloy, and pure lanthanide compounds. Beijerinckiaceae bacterium RH AL1 served as a model organism for an integrated approach combining transcriptomics, analytics, and electron microscopy. This facultative methylotroph depends on light lanthanides for methanol oxidation and forms periplasmic lanthanide deposits. AL1 grew with all tested lanthanide sources and selectively enriched light lanthanides independent of source type, overall lanthanide content, and the proportion of light lanthanides. Transcriptomics revealed that the type of lanthanide source significantly influenced gene expression beyond lanthanide utilization. Lanthanide discrimination in Beijerinckiaceae bacterium RH AL1 is a multilayered process rooted in the complementary action of chelation, uptake mechanisms, and periplasmic storage. Adaptations that increase lanthanide bioavailability transform mineral-bound lanthanides into shared resources within microbial communities, with implications for sustainable lanthanide use.

Microbially mediated Mn() oxidation plays a critical role in regulating the global Mn() cycle and represents an environmentally friendly strategy for remediation Mn() contaminated waters. This study presents the first demonstration that Achromobacter pulmonis ss21, a bacterium isolated from Baiyangdian Lake, exhibits the excellent capacity to oxidze Mn(). The Mn() oxidation efficiency of ss21 reached 98.82% and 97.05% for 200 and 400 mg/L Mn(), respectively. Transcriptome analysis revealed that direct Mn() oxidation was catalyzed by genes encoding copper resistance system multicopper oxidase (HV701_RS04390), LLM-type flavin oxidoreductase (HV701_RS19365) and quinone oxidoreductase (HV701_RS24690), which regulate extracellular electron transfer for continuous Mn() oxidation. In addition, thioredoxin (HV701_RS19360) and glutathione peroxidase (HV701_RS19445) genes maintained intracellular redox homeostasis, ensuring stable and efficient direct Mn() oxidation under high Mn() stress. Moreover, genes (iscU, hscA, fliS, HV701_RS03300, and HV701_RS06395) associated with metabolic support, motility, and transcriptional regulation supported indirect Mn() oxidation. Metabolomics analysis revealed the upregulation of L-Tyrosine, L-Isoleucine, glutamic acid, Gln-His-His, Flavin Adenine Dinucleotide (FAD), xanthine related to ss21 Mn() oxidation, which corresponded to the direct Mn() oxidation genes. This study provides a comprehensive understanding of the molecular mechanisms of biological Mn() oxidation by Achromobacter sp. and highlights its potential application in the bioremediation of Mn contaminated aquatic environments under high metal stress conditions. IMPORTANCEMicrobially mediated Mn() oxidation is a fundamental process in global biogeochemical cycles and offers a sustainable pathway for remediating heavy metal-polluted waters. Achromobacter pulmonis ss21 showed excellent performance in Mn() oxidation. The highly efficient removal of Mn() was achieved through oxidoreductase catalysis, regulation of extracellular electron transfer, maintenance of redox homeostasis, and ensurance of stable and efficient Mn() oxidation under high Mn() stress. Moreover, the Mn() oxidation was supported by metabolites, which prevented irreversible protein damage from oxidative stress induced by high Mn() concentration, alleviating oxidative stress, and stimulating the production of ROS. These findings expand the known diversity of Mn() oxidizing bacteria and offer valuable information for the molecular mechanisms of biological Mn() oxidation.

Bisphenol A (BPA) and Bisphenol S (BPS) exposure disrupt ovarian function and granulosa cell (GC) steroidogenesis. Extracellular vesicles (EVs) and their miRNA cargo, as mediators of cellular response to environmental stimuli, might be involved in fertility and folliculogenesis. This study explored modulation of microRNA expression after 48h BPA or BPS exposure (10 {micro}M) in ovine primary GC and EVs from corresponding conditioned medium (CM EVs). Small RNA sequencing of control (0h) and 48h treated GC, CM EVs as well as follicular fluid EVs allowed identification of 533 ovine miRNAs, including 129 new sequences. BPA did not alter miRNA expression in GC, while BPS decreased cellular oar-24b miR. In contrast, BPA modified expression of 4 miRNAs in CM-EVs, including 3 new sequences, and two miRNAs were modified by BPS. Both compounds reduced expression of sequence homologous to miR-1306. Further studies are required to decipher their roles in bisphenol toxicity in GC.

This study presents the first exploratory assessment of antibiotic resistance genes (ARGs) and antibiotic residues in agricultural environments on Reunion Island, a French tropical territory in the south-western Indian Ocean. Sixteen samples from diverse matrices (manure, soil, water, and vegetables) across different agroecosystems were analyzed using high-throughput qPCR targeting 332 ARGs and chemical methods targeting 58 antibiotic compounds and trace elements. ARGs were widely detected across all matrices, with highest abundance observed in amended soils and manure. Surprisingly, ARG profiles, in terms of both abundance and average number, were comparable between unamended soils and natural soils. Antibiotic residues were found in only five manure and soil samples, with no clear correlation between the presence of these residues, trace elements and ARG abundance. Organic amendments significantly increased ARG levels in soils and non-metric multidimensional scaling revealed that ARG profiles clustered primarily by matrix type rather than by location. High-risk ARGs were widely prevalent, with 86% detected and 23% ubiquitous across all samples, and their occurrence in water and raw vegetables suggests potential human exposure through the food chain. This study highlights the influence of agricultural practices on environmental antimicrobial resistance in tropical island contexts and supports the need for expanded One Health surveillance integrating the environmental, animal and human compartments. SynopsisThis study shows that agricultural practices can shape the environmental spread of antibiotic resistance in tropical island ecosystems, highlighting potential risks for ecosystems, food safety, and human health. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=73 SRC="FIGDIR/small/702181v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@1d07b87org.highwire.dtl.DTLVardef@5e1150org.highwire.dtl.DTLVardef@1c2afe4org.highwire.dtl.DTLVardef@a9be55_HPS_FORMAT_FIGEXP M_FIG C_FIG

Microbial methanogenesis is a major contributor to global warming and methane fluxes represent a loss of energy and electrons from industrial ecosystems. The chemical space of methane control strategies is still under-explored. Most known methanogenesis inhibitors target methanogenic archaeal enzymes. However, interference with syntrophic electron exchange in methanogenic systems presents an additional target for methane control. Here we show that hypophosphite (H2PO2-), an inorganic formate analog, is a potent and selective inhibitor of syntrophic methanogenesis versus primary fermentation in rice field sediments and cattle rumens. Hypophosphite is also generally recognized as safe and relatively non-toxic to plants and animals. Genetic screens and physiological assays in the model methanogen Methanococcus maripaludis S2 implicate formate metabolism as the target of hypophosphite inhibition. Currently, there is no known biological pathway for anaerobic hypophosphite oxidation and hypophosphite is stable in anoxic sediments for weeks to months. Given its widespread natural occurrence, we propose that hypophosphite may modulate carbon cycling in natural environments. Taken together, our results suggest that hypophosphite could be used as a safe, inexpensive, strategy for methane control in syntrophic methanogenic ecosystems.

Accounting for 12% of global solid waste, Poly (ethylene terephthalate) (PET) is one of the most abundantly produced synthetic polymers. While PET offers substantial commercial benefits, its widespread use has led to disproportionate environmental hazards due to its resistance to degradation. To address this problem, several solutions have been proposed, including enzymatic degradation via PETase, MHETase, and Cutinase. Among these, PETase exhibited significant PET-degrading activity. However, the application of PETase has been hampered by its lack of robustness to pH, temperature ranges, and slow reaction rates. Hence, it has become novel enzymes that can overcome these limitations and function efficiently. In this study, we utilised an integrated in silico bioinformatics pipeline to identify and characterise novel PETase candidates from the Thermophilic actinobacteria Thermobifida cellulosilytica and Thermobifida halotolerans species. The PlasticDB database contains 228 plastic-degrading enzyme sequences. In which PETase (00188) is significantly homologous with two putative proteins, Hydrolase (ALF00495.1) and hypothetical protein (WOZ56011.1). The discrete optimized protein energy (DOPE) scores, stereochemical assessments, and homology modeling results closely mirrored our findings for both proteins, supporting their structural stability. The molecular dynamics simulations revealed that the putative ALF00495 variant exhibited more extensive and robust hydrogen-bonding networks, enhanced conformational stability, and increased structural compactness compared to the reference enzyme. The present in silico investigation underscores the potential of putative ALF00495 as a highly effective PETase biocatalyst for polyethylene terephthalate (PET) degradation. Collectively, these findings illustrate the utility of computational approaches of novel PET-degrading enzymes, thereby facilitating the development of sustainable biotechnological strategies to mitigate global plastic pollution.

Air pollution has been increasingly linked to adverse neurodevelopmental and neurodegenerative outcomes. While experimental and preclinical studies suggest that exposure to particulate matter (PM), particularly during gestation, may disrupt cognitive development, the impact of short-term PM exposure on cognitive and behavioral functioning in healthy young populations remains insufficiently explored in Spain. Moreover, few studies have incorporated individualized dosimetry models to estimate exposure more accurately. This study included 186 healthy young adults (mean age = 20.4 years) recruited from three Spanish cities (Teruel, Almeria, and Talavera) characterized by different pollution levels. Ambient fine and coarse PM concentrations were recorded 8, 15, and 30 days prior to psychological assessment. Instead of relying solely on raw in situ environmental measurements, individualized PM deposition was estimated using the Multiple-Path Particle Dosimetry Model (MPPD), allowing a more biologically meaningful exposure approximation. Psychological outcomes were assessed using validated questionnaires: DASS-21 (depression, anxiety, stress), BIS-11 (impulsivity), UCLA Loneliness Scale, and SWLS (life satisfaction). Behavioral performance was evaluated using computerized versions of the Attentional Network Task (ANT) and the Stroop Task. Blood NRF2 concentrations were analyzed as a biomarker potentially related to oxidative stress mechanisms. In situ data indicated that Talavera presented the highest pollution levels, followed by Almeria and Teruel. Linear regression analyses showed that coarse PM exposure across 8-, 15-, and 30-day windows significantly predicted poorer Executive Control Index performance in the ANT. Additionally, 15-day coarse PM and 30-day fine PM exposure were associated with greater cognitive interference. Oxidative stress markers were significantly associated with PM exposure levels. These findings support emerging evidence that short-term PM exposure may negatively affect executive and attentional processes even in healthy young adults. Further longitudinal research incorporating individualized exposure modeling is warranted to clarify causal pathways and underlying biological mechanisms. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=97 SRC="FIGDIR/small/713644v1_ufig1.gif" ALT="Figure 1"> View larger version (79K): org.highwire.dtl.DTLVardef@1a0ac13org.highwire.dtl.DTLVardef@1812accorg.highwire.dtl.DTLVardef@120bf07org.highwire.dtl.DTLVardef@dd9a7c_HPS_FORMAT_FIGEXP M_FIG C_FIG

Antimicrobial resistance (AMR) is a pressing global public health crisis, necessitating novel antimicrobial agents and mechanistic insights. Tetrabromobisphenol A (TBBPA), a widely used brominated flame retardant, exhibits potent activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) without inducing resistance, yet its mode of action remains unclear. Using Bacillus subtilis as a model, we investigated TBBPAs antibacterial mechanism via extensive bacterial cytological profiling, fluorescence imaging, and mutant validation. We found that TBBPA causes membrane depolarization and disruption, based on Thioflavin T release, MinD mislocalization, FM5-95 fluorescence aggregation, and propidium iodide penetration. In fact, TBBPA can destabilizes giant unilamellar lipid vesicles in vitro. The induced membrane damage triggers several downstream effects, including MreB immobilization, which impairs cell wall synthesis, inhibition of DNA replication and translation, and increased autolysin activation leading to cell lysis. In conclusion, this study suggests that TBBPA directly targets the cell membrane, causing disruption of multiple essential processes, and leads to activation of autolysins, resulting in lysis. These findings highlight TBBPAs prospective utility as an anti-Gram-positive agent; nevertheless, concerns over its potential side effects necessitate further investigations into its safety profile prior to clinical translation.

Neurodevelopmental disorders, including autism spectrum disorder (ASD), are influenced by both genetic abnormalities and environmental toxicants. Among environmental risk factors, endocrine-disrupting chemicals such as bisphenol A (BPA) and pharmaceutical drugs such as valproic acid (VPA) have been associated with an increased risk of autism. In this study, human induced pluripotent stem cell (iPSC)-derived forebrain organoids were used to model early neurodevelopmental disruptions induced by BPA and VPA exposure. On day 62 of differentiation, forebrain organoids were treated with physiologically relevant concentrations of BPA or VPA for 28 days. Following treatment, morphological, molecular, and electrophysiological changes were assessed across experimental conditions. Both compounds produced distinct alterations in organoid morphology, neurodevelopmental gene expression, and network electrical activity, with VPA inducing markedly stronger effects. Overall, these data suggest forebrain organoids as a robust, physiologically relevant in vitro model system for studying neurodevelopment. This platform enables systematic investigation of environmental and pharmacological risk factors implicated in the pathogenesis of neurodevelopmental disorders.

Copper is widely used as a fast-acting antimicrobial, yet the strategies that allow bacteria to survive copper stress remain incompletely understood. Here, we characterize the transcriptional responses of Escherichia coli MG1655 to excess ionic copper using RNA sequencing and a genome-wide GFP-based promoter library. We applied 2 mM copper, which slows growth, and 8 mM copper, a near-lethal concentration. RNA-seq revealed extensive transcriptome remodeling, with 487 genes upregulated at 2 mM and 364 at 8 mM. Both concentrations strongly induced canonical copper-responsive systems, oxidative stress defenses, histidine biosynthesis, and multiple iron acquisition pathways - including enterobactin biosynthesis and transport - despite external iron failing to reduce copper toxicity. At 2 mM copper, additional pathways were activated, including heat-shock and protein-folding functions as well as lipid A, methionine and arginine biosynthesis. Copper exposure also repressed large gene sets: 486 genes at 2 mM, enriched for biofilm formation and pH elevation, and 217 genes at 8 mM, enriched for anaerobic metabolism. In contrast to the robust RNA seq results, we investigated the Horizon Discovery E. coli genome-wide GFP based promoter library as an alternative screening tool. However, in our experiments it showed low signal to noise ratios, limiting its suitability for large scale gene expression screening.

Microbial halogenated natural products (hNPs) hold ecological, agricultural, and biomedical relevance. The hNP-producing potential of the organism can be assessed by the precise prediction of biosynthetic enzymes, yet the detailed annotations of halogenases are often missing from genomic and metagenomic data. We created a manually curated database (https://halogenases.secondarymetabolites.org/) containing information on the halide-specificity, role, and position of verified catalytic residues and results of the mutagenesis studies of more than 120 experimentally validated or in silico inferred halogenases. The collection of experimental data supports a computational pipeline that allows the family-, substrate-, and halide-scope-level annotation of halogenating enzymes by relying on catalytic residues, conserved motifs, and profile Hidden Markov Models (pHMMs). Our analysis with sequence similarity networks (SSNs) highlighted several underexplored clusters in the UniRef50 database. Such finding was a halogenase from Rhodopirellula baltica (RhobaVHPO) previously labelled as a hypothetical chloroperoxidase, which clustered apart from the known chloroperoxidases and bromoperoxidases, but accepted chloride and preferred bromide. Our database and workflow provide extensive and scalable solutions for the systematic and precise annotation of halogenating enzymes in genomic and metagenomic data. The in-depth categorization of halogenases will improve the chemical structure prediction of microbial hNPs, supporting ecological assessments and natural product discovery. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/700248v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@ebae51org.highwire.dtl.DTLVardef@10188f0org.highwire.dtl.DTLVardef@1c55684org.highwire.dtl.DTLVardef@b311bd_HPS_FORMAT_FIGEXP M_FIG C_FIG

Increasing levels of nanoplastics (NPLs) in the environment raise concerns about their effects on human health. We investigated the impact of the most prevalent NPLs, namely polyethylene terephthalate (PET) and polystyrene (PS), on stem cells (SCs), which persist for decades, support tissue function, and are often implicated in cancer development. Long-term exposure to both NPLs similarly affected mammary SC features with an enhanced self-renewal and altered 3D organization, without impairing differentiation capacity. Moreover, both NPLs significantly increased invasiveness and anchorage-independent growth, albeit molecular profiling revealed distinct signatures and mechanisms, indicating a shift towards a more aggressive phenotype. NPLs also synergized with BMP2 signaling, known to be disrupted by pollutants. These findings highlight how NPLs may contribute to early pre-neoplastic changes through distinct and cooperative mechanisms.

Paralytic Shellfish Toxins (PSTs) are produced by certain species of cyanobacteria and dinoflagellates. Part of the PST biosynthetic pathway has been elucidated in cyanobacteria, and the implication of some sxt genes has been confirmed by experimental studies. Contrary to cyanobacteria, knowledge about PST biosynthesis in dinoflagellates is more limited and generally restricted to comparative studies with the cyanobacterial pathway. To investigate the specificity of the PST pathway in dinoflagellates, 16 toxic and non-toxic A. minutum strains from a recombinant cross were compared, without prior assumption on genes or metabolites involved in PST synthesis, using an integrative approach combining untargeted metabolomic and transcriptomic data. Among the 60 most distinguishing transcripts between toxic and non-toxic strains, only 3 sxt genes were present, sxtA4, sxtG, and sxtI. In contrast, non-sxt homologs were detected as highly discriminant between these two phenotypes. More specifically, a phyH homolog may act as the analog of sxtS found in cyanobacteria. Moreover, we identified four putative synthetic PST intermediates. Among these, Int-C2, correlated with the toxic phenotype, whereas 3 others were detected in both toxic and non-toxic strains, suggesting that these strains may share some parts of the biosynthetic pathway. Finally, our results showed that PST biosynthesis in dinoflagellate results from the activity of sxt genes, acquired by horizontal gene transfer from cyanobacteria, as well as from other genes not acquired from cyanobacteria, such as phyH.

Sustainable aquaculture requires comprehensive chemical oversight, as compounds used in aquaculture can persist in ecosystems, bioaccumulate through food chains, and affect aquatic life and human health. This study presents ReCAnt (Resource on Chemicals used in Aquaculture and their Ecotoxicity), which compiles information on 690 aquaculture chemicals, with data on toxic effects and therapeutic potential curated from published literature. It was observed that only a fraction of the 690 chemicals are currently regulated, revealing gaps in existing regulations. Integration of data from the Comparative Toxicogenomics Database revealed associations with genes, phenotypes, and diseases, while ECOTOX data provided toxicity and bioconcentration information. Predicted biotransformation pathways and partition coefficients indicated microbial degradation potential and fate across environmental media. Further, food web network analysis identified species vulnerable to trophic transfer and common entry points for chemicals into aquatic ecosystems. This resource can aid in developing evidence-based regulatory frameworks and promoting sustainable chemical management.

The global industrialization and rapid urbanization elevated the risk of toxic pollutant exposure, which affects human health specially during pregnancy. Pregnant mothers are daily exposed to bisphenol-A (BPA), which is a common plastic leachate and a prominent toxic pollutant present in our environment. BPA act as an endocrine disrupting chemical (EDCs) by altering feto-placental homeostasis. This persistent and potent exposure of BPA during gestation can trigger placental damage affecting trophoblast cell function and survival. BPA even disrupts specific signalling cascades by altering post translational protein phosphorylation. However, this BPA mediated dysregulation of signalling nodes in early trimester placenta is still unexplored. Therefore, this study investigates the global proteome changes in post-BPA exposed extravillous trophoblast (EVTs) cells, which revealed a BPA mediated dynamic regulation of phosphoproteome-signatures and their associated kinases. Further inspection showed that the altered phosphorylation of c-JUN (S63) and GSK3 (Y279) is associated with BPA toxicity in EVTs and placenta. This altered phosphorylation affects the cellular signalling downstream, imparting damage upon the growing feto-placental unit. This highlights an altered phosphorylation mediated mechanism of BPA toxicity in placenta which can cause an onset of adverse pregnancy outcome. Data are available via ProteomeXchange with the identifiers PXD074780.

There is a growing concern that chronic, low-level exposure to organophosphate insecticides is a threat to human health. These synthetic chemicals are used in crop and livestock production all over the world, and the general population are exposed to them through consuming the residues that remain in food. Evidence is emerging that fermentation with lactic acid bacteria may be an effective way of reducing organophosphate insecticide residues. However, while several studies have investigated this topic, outcome measures have varied, and there has been no research to date which has consolidated this data to better understand the half-lives of organophosphate insecticides in fermented foods and the factors affecting degradation. The aim of this review was to synthesise the evidence on organophosphate insecticide degradation during lactic acid fermentation, and analyse organophosphate insecticide half-lives, in order to determine the effectiveness of lactic acid fermentation in reducing organophosphate insecticide residues in food. Furthermore, the study aimed to explore the factors that impact the rate of degradation. CAB Abstracts, Food Science and Technology Abstracts, Scopus and Web of Science were searched for eligible laboratory-based studies, which were published after 2000. The literature search and screening process resulted in the inclusion of 14 eligible studies. Studies were screened for Risk of Bias (ROB) using the RoBDMAT tool. Collated results showed that organophosphate insecticides degraded over time, and this was irrespective of fermentation. However, out of the 249 experiments that involved a controlled fermentation, 232 demonstrated that fermentation with lactic acid bacteria could speed up the degradation of organophosphate insecticides in food, beyond the rate of inherent degradation in the food matrix, leading to shorter half-lives. The half-lives of organophosphate insecticides in apple juice, milk and wheat ranged from 9.5 hours to 21 days in fermented foods and ranged from 21.4 hours to 36.5 days in non-fermented foods. Single species of lactic acid bacteria that demonstrated strong potential for organophosphate insecticide degradation were Lpb.plantarum subsp.plantarum, Lab.delbrueckii subsp.bulgaricus and Lvb. brevis, where the median percentage change in organophosphate insecticide half-life during fermentation was -42.3%, -25.0% and -22.9%, respectively. Organophosphate insecticide degradation during natural fermentation was less clear because of fewer studies and less consistent results. Whilst the collated data shows that fermentation with lactic acid bacteria is an effective method to reduce organophosphate insecticide residues in food, reflected in shorter half-lives, the small number of studies and variability among studies does limit the conclusions that can be drawn, and further research is needed to strengthen these findings. The results of our analysis may help to inform more reliable organophosphate exposure assessments for the population as well as provide novel insights for both consumers and food manufacturers, expanding the market potential for fermented foods.

Uranium (U) and arsenic (As) are both ubiquitous contaminants in the American southwest, posing risks to humans, animals, and the environment. Depleted uraniums (DU) chronic effects and mechanisms of toxicity are incompletely understood. Differential gene expression of concomitant exposures to identify markers of toxicity have not been undertaken until now. Continuous low-dose, high-dose, and concomitant exposures are investigated using the larval zebrafish (Danio rerio), with exposure paradigms lasting from embryo collection until sampling at 5 days post fertilization (dpf). Herein, we describe overall differential gene expression with counts and pathway enrichment statistics using both gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The raw dataset has been deposited in NCBIs Gene Expression Omnibus (GEO) repository [1] under the accession number GSE319292 [2]. O_TBL View this table: org.highwire.dtl.DTLVardef@9b121aorg.highwire.dtl.DTLVardef@c17073org.highwire.dtl.DTLVardef@1bdc2b9org.highwire.dtl.DTLVardef@13b130aorg.highwire.dtl.DTLVardef@15f1d22_HPS_FORMAT_FIGEXP M_TBL C_TBL VALUE OF THE DATAO_LIUranyl nitrate (UN), a water-soluble depleted uranium species, and sodium arsenite (As) are both ubiquitous contaminants in the American southwest, posing risks to humans, animals, and the environment. The United States Environmental Protection Agency (EPA) has set maximum contaminant limits (MCL) of 30 ppb U atoms and 10 ppb As atoms, respectively. C_LIO_LIThese data show differentially expressed genes (DEGs) from larval zebrafish exposed to 1 or 10 {micro}M As, 30 or 300 {micro}g/L UN, or 1 {micro}M As and 30 {micro}g/L UN in combination. Concentrations were specifically chosen based on environmental relevance. C_LIO_LIGene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of up- and down-regulated DEGs are provided to understand the molecular mechanisms of uranium toxicity and inform future studies. C_LIO_LIThese data should be used for biomarker identification and mechanistic interrogation of single and combinatorial exposures of environmentally relevant compounds at realistic exposure levels. C_LI

Electrolytic hydrogen water (EHW) plays a critical role in modulating cellular metabolism; yet, the underlying molecular mechanisms remain unclear. This study utilized next-generation sequencing (NGS) to assess mRNA and miRNA expression in EHW-treated Caco-2 cells. Bioinformatics analysis identified differentially expressed genes (DEGs) and pathways influenced by EHW and highlighted its involvement in the oxidative stress response and tight junction formation. Protein-protein interaction (PPI) network analysis of the DEGs identified first-neighbor genes, supporting the role of EHW in suppressing oxidative stress-related genes while also enhancing the expression of the TCEB2-CUL5-COMMD8 (ECS complex) genes, both of which converged on the HIF-1 signaling pathway. We also constructed an mRNA-miRNA competing endogenous RNA (ceRNA) network, which revealed four hub genes, two non-coding RNAs (miR-429 and miR-200c-3p) and two protein-coding RNAs (CUL5 and GOLGA7). These genes co-target the transcription factor KLF4 in Caco-2 cells, forming a TF-miRNA-gene network (TMGN). EHW treatment significantly decreased the levels of miR-429 and miR-200c-3p and stabilized CUL5 and GOLGA7 transcripts post-transcriptionally as compared to ACW. Concurrently, reduced miRNA expression weakened their pre-transcriptional competition with mRNAs for KLF4 binding, further enhancing CUL5 and GOLGA7 expression. Phenotypic assays confirmed that continuous EHW treatment promotes Caco-2 cell differentiation. This study underscores the regulatory role of EHW in intestinal cells via feed-forward loops (FFLs), offering novel insights into the molecular mechanisms and functions of EHW. HighlightsO_LIIdentification of Novel Key Regulatory Genes Modulated by Electrolytic Hydrogen Water (EHW) Treatment: PPI network analysis demonstrated that EHW downregulates mitochondrial oxidative metabolism-related genes while upregulating TCEB2-CUL5-COMMD8 (ECS complex) expression within the HIF-1 axis. C_LIO_LIConstruction of a ceRNA Network: By integrating transcriptome and miRNA sequencing data from EHW-treated samples, we assembled an associated network and identified four hub genes in intestinal cells within the mRNA-miRNA ceRNA network: miR-429, miR-200c-3p, CUL5, and GOLGA7. C_LIO_LINovel Mechanistic Insights of Post- and Pre-Transcriptional Regulation by EHW: We identified KLF4 as a key transcription factor regulating EHW hub genes and constructed a TF-miRNA-gene (TMGN) feed-forward loop (FFL) network, offering new insights into EHW biomarkers. Our analysis revealed that EHW reduces miR-429 and miR-200c-3p levels, thereby enhancing CUL5 and GOLGA7 expression through both pre-transcriptional and post-transcriptional regulation. C_LIO_LIPhenotypic Confirmation: Continuous EHW treatment shortened the time required for Caco-2 cell differentiation. C_LI