Ecotoxicology and Environmental Safety

Background: Men with prostate cancer (PCa) may be especially vulnerable to per- and polyfluoroalkyl substances (PFAS) exposure due to their endocrine-disrupting and cardiometabolic impacts and cardiotoxicity and immune suppression of treatments. Objective: A pilot study was launched to measure serum and tap water PFAS concentrations in PCa survivors. Methods: Men with PCa were recruited from Rutgers Cancer Institute between February 2025 and March 2026, with ongoing enrollment and follow-up. Eligible men were aged [≥]40 years and either on active surveillance or within 3-12 months of initial definitive treatment. Participants provided blood and residential tap water samples, which were analyzed using mass spectrometry (serum) and modified EPA method 537 (water). Geometric means were used to summarize PFAS concentrations by race and assess serum-tap water correlations. Results: Of 235 eligible patients, 124 (60%) enrolled. Median age was 64 years; 63% were non-Hispanic White, 43% had a Gleason score [≤]6. Roughly half of participants provided serum and/or tap water samples. In serum, six PFAS analytes had >80% detection; of these analytes, median concentrations ranged from 0.13 ng/mL (IQR: 0.07-0.20) for PFHpS to 2.55 ng/mL (IQR:1.54-3.82) for nPFOS. Among 74 tap water samples, 9 PFAS analytes had >60% detection; of these, median concentrations of PFNA (0.56 ng/L; IQR: 0.33-0.75), PFOA (3.75 ng/L; IQR: 1.21-5.27), and PFOS (2.29 ng/L; IQR: 0.46-2.89), were below New Jersey Maximum Contaminant Levels. Non-White participants had significantly higher levels of multiple PFAS analytes in both serum and tap water. Serum-tap water correlations were modest (r=0.22-0.41). Significance: The pilot study has demonstrated both the feasibility and importance of studying PFAS exposure pathways as well as potential impacts of PFAS exposure in diverse populations. Keywords: Prostatic Neoplasms, Per- and Polyfluoroalkyl Substances (PFAS), Biomonitoring, Environmental Exposure, Cohort Studies, Pilot study Impact Statement: This study provides some of the first estimates of PFAS exposure among prostate cancer patients in serum and tap water, showing moderate correlations between tap water and serum concentrations of specific PFAS analytes. These findings can support larger studies to identify environmental exposure sources and evaluate the role of PFAS in prostate cancer progression and outcomes.

Fine particulate air pollution (PM2.5) in the United States has fallen by roughly half since 2000, yet linked health outcomes such as diabetes and childhood ADHD have not improved in parallel. One reconciling possibility is that pollution exposure in early life produces health effects that emerge only years or decades later, after pollution itself has declined. Using two decades of U.S. county-level data, we relate annual PM2.5 estimates to birth outcomes, diabetes prevalence, and small-area estimates of childhood attention-deficit/hyperactivity disorder (ADHD) across short and long time scales. Within counties, changes in low birth weight rates are associated with changes in PM2.5 during the same year and the year prior to birth. At longer time scales, cross-county comparisons show that PM2.5 exposure is associated with higher prevalence of adult diabetes and ADHD after approximately a decade. Together, these patterns suggest that population-level health risks from air pollution may persist over decades, even as pollution itself declines.

Abstract Background. Chronic low-level exposure to lead, cadmium, mercury, and arsenic remains a determinant of premature mortality in the U.S. general population, but previous hazard-ratio analyses do not characterize how exposure shifts the lower tail of the survival distribution, where premature mortality is concentrated. Objectives. We estimated the association of whole-blood lead, whole-blood total mercury, urinary cadmium, and the sum of urinary inorganic and methylated arsenic species with the 10th, 25th, and 50th conditional quantiles of follow-up time to all-cause mortality among U.S. adults aged 40 years and older. Methods. NHANES Continuous 1999 to 2018 was linked to the National Death Index through December 31, 2019 (n = 29,652). Censored quantile regression was fit per metal on the log2 scale at quantiles {tau}{0.10, 0.25, 0.50}. A restricted-cubic-spline (RCS) censored-quantile-regression was fit for blood lead and urinary cadmium to investigate the threshold effect. Results. Over a median follow-up of 9.1 years, 7,215 deaths were ascertained. A doubling of urinary cadmium was associated with -1.57 years of follow-up (95% CI: -2.08, -1.07) at the 10th conditional quantile, -1.50 (-2.04, -0.96) at the 25th, and -1.49 (-1.93, -1.04) at the median (Benjamini Hochberg q < 0.001 throughout). A doubling of whole-blood lead was associated with -0.70 years (95% CI: -0.99, -0.40) at the 10th conditional quantile, -0.62 (-0.92,-0.31) at the 25th, and -0.61 years (-0.89, -0.34) at the median; the absolute loss was largest at {tau} = 0.10 for both metals. Urinary arsenic-metabolite sum was not associated with conditional follow-up at the estimable quantiles. Despite adjustment for dark and fatty-fish intake or DHA/EPA, whole-blood total mercury was associated with longer follow-up (i.e., negatively associated with mortality risk), possibly due to residual confounding by broader dietary or socioeconomic factors, rather than a true protective effect. The cadmium association was additionally robust to the mutual adjustment of lead. Discussion. Low-to-moderate urinary cadmium and whole-blood lead were associated with fewer years of follow-up survival at the lower-tail and median conditional quantiles of survival, with the largest absolute losses at the lower tail of the conditional survival distribution, where premature mortality is concentrated. These findings support continued reductions in U.S. cadmium exposure and lead with particular benefit for adults most vulnerable to premature death.

Tenuazonic acid (TeA) is an emerging Alternaria mycotoxin frequently detected in food and feed commodities, raising concerns about its toxicological relevance. Chronic oral exposure to TeA has been reported to induce dysplastic alterations in the esophageal mucosa of mice, while human biomonitoring data indicate an association between TeA exposure and esophageal cancer, although a causal relationship has not yet been established. At a mechanistic level, the effects of TeA in esophageal cells remain poorly characterized. Therefore, this study investigated the impact of TeA on cytotoxicity, oxidative stress, DNA damage, mitochondrial homeostasis, cell-cycle distribution and transcriptomic stress responses in human esophageal KYSE-510 cells. TeA induced a concentration-dependent reduction in metabolic activity and total protein content after 24 h exposure to 0.1-100 M. Significant cytotoxicity was measured starting from 20 M. At sub-cytotoxic concentrations, TeA triggered rapid ROS formation within 5-30 min exposure and induced formamidopyrimidine-DNA glycosylase (FPG) sensitive DNA damage after 1 h exposure (5-7.5 M), indicating oxidative DNA lesions. In addition, TeA altered mitochondrial morphology after 4 h exposure at 7.5 M, manifested by shrinkage of the mitochondrial network area and perinuclear redistribution, while mitochondrial respiration showed only a non-significant tendency towards reduced respiratory capacity. RNA sequencing after 6 h exposure to 10 M TeA revealed oxidative stress-associated transcriptional changes, impaired antioxidant and stress-adaptive responses, and p53-associated stress signaling. Furthermore, TeA induced significant G2/M phase accumulation after 24 h exposure to 1-10 M.

Depleted uranium (DU) is an environmental contaminant with a 30 g/L (ppb; parts per billion) EPA maximum contaminant level (MCL) for drinking water. The mining of uranium and use of DU in modern weapons underly human exposure that disproportionally impacts military and tribal communities in the United States. Uranium's radiotoxic characteristics are understood, but its chemical hazards much less so. In zebrafish (Danio rerio) and human cell cultures we test the hypothesis that exposure to DU negatively impacts cellular function and development through disruption of mitochondrial metabolism. Using a novel shrapnel model with TEM/SEM+EDS, we showed uranium microparticles caused proximity-dependent mitochondrial disruption. In waterborne exposure paradigms, larval movement was reduced and hatching delayed as a result of reduced movement and not enzyme deficiencies in response to 18 ppb DU, below the MCL. Increased DNA damage accumulation was detected in exposed larva and cells. DNA-damage quantitative PCR of DU-exposed larvae showed increased damage in the ahr1 locus (nuclear gene) and decreased mitochondrial DNA (mtDNA) copy number, but mtDNA damage levels varied across experiments. Mitochondrial function was assessed using a resazurin-based assay in the presence and absence of antioxidants and showed diminished cytoplasmic reductive capacity. DU exposure alone did not enrich antioxidant gene expression, contrasting with arsenic exposure, a known ROS-inducer and Nrf2-activator. Sulforaphane (SFN), a potent Nrf2-activator, did not blunt the effects of DU exposure, despite activation of antioxidant response element (ARE) genes (gstp and gss), but did blunt the effects of arsenic exposure. The most enriched transcript in DU-exposed larvae coded for slingshot protein phosphatase (ssh), further exploration revealed ssh1b as the zebrafish-specific ortholog activated in response to DU, and inhibition using an identified SSH1 inhibitor, Sennoside A, partially rescued the metabolic and hatching defects observed. Our data points to a cytotoxic mechanism in which DU disrupts mitochondrial function through ssh1b enrichment that impairs normal mitophagy, leading to decreased cellular reductive potential independent of either ROS production or ARE-activation. Our results suggest that health impacts from DU exposure may be directly linked to impaired mitochondrial functions.

Wood is commonly used in the building sector, emitting volatile organic compounds (VOCs) contributing to indoor air quality. These VOC profiles can have a pleasant smell and positive effects e.g., induce relaxation. Contrarily, VOCs can have adverse health effects in higher concentrations. Therefore, some VOCs are regulated by guide values (GV). Potentially positive and negative effects of pinewood emissions, ranging from 0.2 mg/m3 (German GV I for bicyclic terpenes) to 2.0 mg/m3 (GV II) were investigated in an experimental 2 h exposure study using a within-subject design. Thirty-two healthy participants rated the perception, pleasantness, symptoms of irritation, and indicators of well-being. During a demanding working memory task (n-back) and a resting period, heart rate (HR) and HR variability (HRV) changes were measured. Before and after each session physiological markers of sensory irritation were assessed. Ratings indicated that the exposure to GV I and GV II were not perceived as more intense or pleasant. Mostly concentration-independent effects were revealed, indicating that inter-individual factors influenced the ratings rather than the VOCs. The pinewood odors during the n-back task did not cause distraction nor did it facilitate performance as previously suggested. HR/V changes indicated that pinewood odors during and after the n-back tasks did not induce relaxation. Only symptoms of nasal irritation showed some weak concentration-dependency, not supported by physiological markers or comparable ratings of sensory irritation. In conclusion, the fact that no distinct odor is detected suggests that interfering factors potentially prevent the regulation of odors at relevant indoor air concentrations.

Background: Human activities such as mining generally lead to increased heavy metal concentrations in the environment. While traditional remediation techniques are often costly, the use of fungi as bioremediators, known as mycoremediation, is increasingly gaining attention as a sustainable approach for removal of heavy metals. Here, we evaluated heavy metal levels inside the Kiirunavaara iron ore mine in Northern Sweden and analysed fungal responses to various metal concentrations by comparing growth and metal uptake in mine-derived isolates and closely related control isolates. Results: Sediments inside the mine were enriched in heavy metals compared to those from the outlet of the mine to natural lakes. Six Fusarium isolates were recovered from contaminated mining environments: five isolates from inside the mine were identified as Fusarium oxysporum, and one isolate from the outlet was identified as Fusarium tricinctum. Isolates from the mine and outlet showed overall higher survival and biomass production in presence of copper, iron, and zinc across a range of concentrations (up to 1000 mg/L) compared to control isolates. At the same time, these isolates often exhibited reduced relative metal uptake. As a result, mycoremediation potential, assessed as total uptake in the grown mycelium, was isolate-dependent. Conclusions: Based on these results, we conclude that Fusarium isolates from the Kiirunavaara mine show increased growth in media enriched with heavy metals compared to closely related control isolates. We additionally show that mycoremediation potential is not necessarily associated with environmental origin. Instead, mycoremediation potential should be evaluated on a case-by-case basis for each isolate and based on specific needs for mycoremediation.

While exposure to volatile organic compounds such as ethylene dichloride and vinyl chloride monomer is a well-established cause of liver disease, particularly hepatic hemangiosarcoma, characterizing real-world exposure profiles in communities surrounding industrial centers remains challenging. Calvert City, Kentucky (population ~2,500), provides a unique setting characterized by both active industrial emissions and legacy sources of air toxics. To address these complexities, this method paper describes the framework for the Biomonitoring and Environmental Assessment for Community Outreach and Neighborhood Safety (BEACON) study. By utilizing a novel, multi-dimensional exposure assessment strategy, BEACON aims to characterize air toxic exposures and provide actionable data for community health and safety. For the BEACON study, we will leverage Kentucky Department of Air Quality measures of air toxics, analyze urine samples in a small cohort of community volunteers, analyze community urine via wastewater in an adjacent community, geocode citizen odor reporting, assess blood markers in wildlife, survey small and large animal veterinarians in the area for anomalies in morbidity and mortality, and work with the regional health system to enhance vigilance for health issues associated with toxicants present in the area. In addition, blood samples will be collected at three time points and biobanked for future analyses. Efforts will be made to link this study to additional large-scale long-term cohorts where possible. Throughout the project, community engagement will play a critical role by raising awareness, fostering collaboration, and ensuring that the voices of affected residents are heard.

Humans and other vertebrates contain two estrogen receptors (ERs), ER-alpha and ER-beta, which mediate the physiological actions of three estrogens: estrone (E1), estradiol (E2) and estriol (E3). Of these three estrogens, in vivo, E2 is the strongest transcriptional activator of ER-alpha and ER-beta, E1 is next most active, followed by E3. We studied transcriptional activation of human ER-alpha and ER-beta by E2, E1 and E3 in African green monkey kidney (COS-7) cells, which we compared with studies of estrogen stimulation of ER transcription in human em-bryonic kidney (HEK-293) cells. To our surprise, in COS-7 cells, E3 had the lowest half-maximal response (EC50) for human ER-alpha and ER-beta than either E2, which was second most active estrogen, or E1. In contrast, for human ER-alpha and ER-beta transfected into HEK-293 cells, E2 was the most active estrogen, followed by E1 and E3. Similar results were found in COS-7 cells and HEK-293 cells transfected with elephant shark ER-alpha and ER-beta. Thus, under some conditions, E3 is a more active estrogen than either E2 or E1. This suggests that E3 may be a novel physiological ligand for the ER in some mammalian cells.

Microplastics are pervasive environmental pollutants increasingly implicated in adverse human health effects, with emerging evidence linking MPLs exposure to elevated cardiovascular risk, including atherosclerosis. However, their specific mechanisms of action remain unknown. Human aortic endothelial cells (HAECs), located in the innermost layer of blood vessels, play a crucial role in maintaining vascular homeostasis and the development of atherosclerosis. This study demonstrates that polystyrene microplastics (80 nm MPLs) can enter HAECs through multiple pathways, including macropinocytosis, clathrin-mediated endocytosis, and caveolin-mediated endocytosis, and co-localize with mitochondria and lysosomes. MPLs exposure resulted in coordinated transcriptional, epitranscriptomic, and metabolomic reprogramming in HAECs, characterized by disruption of mitochondrial genes and an inflammatory response with activation of TNF-a; and NF-kB signaling. Integrative analysis revealed remodeling of the epitranscriptomic profile, demonstrated by an increase in 1-methyladenosine (m1A) modification along with reciprocal regulation (TRMT61A upregulation and ALKBH3 suppression) of its transcriptomic machinery, alongside other enzymes associated with 3-methylcytidine (m3C), pseudouridine (Y), 5-methylcytidine (m5C), and 7-methylguanosine (m7G) pathways. By comparing transcriptomic data from MPLs-treated HAECs with those of human atherosclerotic plaques, several common dysregulated pathways were identified, particularly those related to vascular physiological regulation and cell signaling. Metabolomic profiling further revealed significant remodeling of lipid metabolic networks associated with oxidative stress and inflammatory signaling. In summary, this study reveals that HAECs can internalize MPLs, leading to multiple disturbances in the transcriptome, epigenome, and metabolic networks, suggesting that MPLs exposure may pose a potential hazard to human cardiovascular health.

Introduction The Tobacco and Vapes Act 2026 provides the UK government powers to ban vaping in public places. Proposals include extending existing indoor smoke-free legislation to also being vape-free and making public children's playgrounds and outdoor areas of education settings vape-free. We examined adults' and adolescents' views on vape-free places. Methods Two UK-wide cross-sectional online surveys were conducted in 2026, one with adult (18+) current and former nicotine users (n=2,851), and one with adolescents aged 11-17 years (n=2,123). We measured (1) perceived acceptability of vaping in public places, (2) views on whether vapes should/should not be allowed in public places, and (3) perceived likelihood of public compliance with vaping bans. Results Adults considered it unacceptable to vape on public transport (85.9%), on school grounds (outdoors) (83.6%), outside hospital entrances (59.2%), and inside pubs (57.8%) and nightclubs (52.5%). A minority considered it unacceptable to vape at open air playparks (40.6%). Most adolescents viewed vaping as unacceptable in all locations. Perceived acceptability of vaping in each place was associated with current vaping and/or smoking. Adults and adolescents believed vaping should not be allowed on public transport (88.9%; 93.8%) or outdoors on school grounds (85.8%; 93.5%). Adults and adolescents perceived likely compliance on public transport, school grounds and in pubs, but not in nightclubs, outside hospital entrances and at open air playparks. Conclusion The findings indicate public support for some vape-free places among adults and adolescents, particularly on public transport and school grounds, and less so for a ban at open air playparks.

Introduction: Pediatric nicotine exposures remain an important and preventable public health issue, particularly with the rapid expansion of electronic nicotine delivery systems. This study compared demographic characteristics, exposure circumstances, and clinical outcomes between pediatric cases involving nicotine devices and bottled liquids reported to U.S. poison centers. Method: This retrospective cohort study analyzed National Poison Data System cases from 2011-2022 involving children aged less than 6 years exposed to nicotine devices or bottled liquids. Analyses were limited to cases with definitive medical outcomes. The primary outcome was defined as a moderate or major clinical effect or death. Odds ratios with 95% confidence intervals were calculated, with a secondary analysis restricted to route-concordant exposures. Results: The final cohort included 15,497 cases: 10,168 device exposures and 5,329 liquid exposures. Demographic characteristics were similar between groups. Device exposures more frequently involved inhalation, while ingestion predominated overall. Clinical effects were typically mild and transient, with vomiting and coughing most commonly reported. The primary outcome occurred in 1.9% of device cases and 2.0% of liquid cases (OR = 1.05; 95% CI 0.82-1.34). A secondary analysis restricted to inhalation-only device exposures and ingestion-only liquid exposures similarly found no significant difference in clinically important outcomes (OR = 1.38; 95% CI 0.92-2.12). Two deaths occurred, one in each group. Conclusion: These findings suggest that, despite differences in formulation and route of exposure, nicotine devices and bottled liquids produce broadly similar clinical toxicity profiles in young children. Prevention strategies should address all household nicotine products rather than focusing on specific delivery systems.

Lipid peroxidation (LPO) is widely used as a biomarker of oxidative stress in coral bleaching research, yet its measurement remains poorly standardized across the field. A systematic review of the coral LPO literature reveals substantial variation in methodological approaches, including tissue fraction analysis, lysis protocols, assay choice, and normalization metrics, confounding cross-study comparison and obscuring the biological interpretation of results. We experimentally investigate two key sources of variation: the use of bulk holobiont vs separated host and algal symbiont fractions, and the choice of normalization metric. To do so, we used Montastraea cavernosa (n = 6 colonies) exposed to ambient (28C), heat stress (30.5C), and heat stress + artificial upwelling (AU; heat stress intermitted by daily pulses of cooler water, 30.5/27.5C) conditions in a controlled mesocosm experiment. Using a TBARS-based MDA assay with a lysis buffer optimized for coral tissue, we measured LPO separately in coral host and algal symbiont fractions across four time points throughout the day. Host MDA remained stable across all treatments and time points, consistent with either sufficient antioxidant buffering capacity or thermal acclimation over the experimental period. Algal symbiont MDA, in contrast, exhibited pronounced diel and treatment-specific dynamics, and the two fractions responses were decoupled from one another. Normalizing MDA to coral surface area instead of total protein content produced largely consistent diel and treatment patterns, but the two metrics diverged at specific time points, indicating that normalization choice is not interchangeable and can itself affect interpretation. Together, our literature review and empirical results demonstrate that host and algal symbiont LPO dynamics are not comparable when aggregated and argue for host-symbiont fraction separation and consistent, explicitly reported normalization as minimum standards for interpretable and cross-comparable coral LPO measurement.

Melanins are biological macromolecule with immense functionality synthesised by a wide spectrum of living organism. It is mainly synthesised by the oxidative polymerization of indolic and phenolic compounds through several enzymatic process. It has wide spread application in agriculture, cosmetic and therapeutic industry due to its various properties including antioxidation ability, UV protection efficiency and anticancer activity. Because of this wide range of application in different sectors, large scale production and commercialization attains enormous consideration. The present study deals with the effect of 12 different process parameters on melanin production viz., production media, incubation time, inoculum concentration, pH, temperature, agitation, carbon source, phosphate and magnesium source, CuSO4.5H2O, sodium chloride and L-tyrosine on melanin production by Pseudomonas stutzeri strain BTCZ 109 obtained from Arabian sea sediments was evaluated. After optimizing the important process parameters, the bacteria showed about ~4.65 fold increase in melanin production compared to unoptimized cultural conditions. The melanin optimized through this method was found to be nano sized. The Nano sized DOPA melanin in treating Skin cancer cell line SK ML28 which showed a dose-dependent activity with an IC50 value of 164 g/mL. All these results highlight the therapeutic efficiency of DOPA melanin Nano particle as promising bioactive molecule.

Metabolites from Plantago lanceolata (plantain) biomass have been linked with biological nitrification inhibition (BNI) in soil. After grazing, leaf metabolite chemistry is altered via digestion, and a suite of secondary metabolites are then delivered onto soil via dung and urine. The purpose of this study was to establish if urine from sheep grazed on plantain had BNI activity when added to pasture soil, and to identify the metabolite profile(s) that most likely contribute to the BNI effects observed. Groups of sheep (n=5) were grazed on one of nine different plantain cultivars in autumn and spring with analysis of leaf material, urine, soil incubation and BNI bioassay data used to identify potential metabolite candidates implicated with BNI. The urinary nitrogen and metabolite composition of sheep fed plantain varied significantly between cultivars and season. After 28 days of incubation, all soil microcosms treated with plantain-derived urine had up to 35% less nitrate than comparative ryegrass urine controls in both seasons, except one in autumn. The key phytochemistry associated with lower soil nitrate concentrations was phenylethanoid and iridoid glycosides resulting in a higher output of glucuronidated, methylated and sulfated secondary metabolites in the urine. Among 19 secondary metabolites identified in the urine, hydroxytyrosol-related metabolites as well as catechol glucuronide, 2-methoxyphenyl sulfate and guaiacol-{beta}-D-glucuronide appear to be the most likely target compounds with respect to the BNI effects observed. Variation in metabolites from different plantain cultivars affected the ratio of metabolite derivatives in urine, which ultimately affected soil nitrification rates. Cultivar phytochemistry is therefore an important consideration with respect to BNI under urine patches. HighlightsO_LISheep grazing different plantain cultivars had different urine compositions C_LIO_LIUrines elicited biological nitrification inhibition (BNI) in soil and in vitro C_LIO_LIDifferent BNI response was related to differential expression of urine metabolites C_LIO_LIKey urine metabolites associated with BNI are derived from glycosidic compounds C_LI

The development of cost-effective, serum-free media is critical for scalable cultivated meat production. This study used high-throughput screening through a Design of Experiments (DoE) approach to develop an animal-free, serum-free medium (MMM1) specifically for the C2C12 murine myoblasts model cell line with applicability in cultivated meat research including for pet food. Low cost, food-grade inputs such as methylcellulose and spirulina extract resulted in significant cell growth improvements. The optimised MMM1 formulation containing low cost, food-grade inputs, achieved cumulative population doublings comparable to 10% (v/v) fetal bovine serum over four consecutive passages. Furthermore, MMM1 supported scalable cell expansion on commercially available dextran-based microcarriers (Cytodex-3) in both static and agitated conditions in spinner flasks, matching growth rates of serum-based controls. Finally, transitioning to a food-grade DMEM/F12 basal medium maintained cell proliferation equivalent to the pharmaceutical-grade DMEM/F12, but at a significantly lower cost, thus offering a viable strategy to substantially reduce biomanufacturing costs which is a critical challenge in cultivated meat production.

Class imbalance remains a challenge in metabolomics research, where biological and technical variability can affect statistical inference and machine learning (ML) performance. Class-balancing algorithms address this issue by either increasing minority-class observations or reducing the number of majority-class samples. This study evaluated the impact of oversampling and undersampling algorithms on targeted and untargeted metabolomics datasets derived from LC-MS and GC-MS analyses of plasma samples from patients with glioblastoma, meningioma, and controls. Synthetic Minority Oversampling Technique (SMOTE) and Random Undersampling (RUS) were applied to balance the datasets, and their effects on data distribution, inter-feature correlations, and machine learning model performance were compared. RUS preserved the original feature distributions but reduced representativeness by removing the majority-class samples. In contrast, SMOTE introduced synthetic samples that altered covariance structures, increasing the risk of overfitting, particularly in small datasets (n=10). These effects diminished with larger groups (n=30), partially restoring correlations between metabolites. Model performance varied across the class-balancing algorithms. Random Forest classifiers benefited from both balancing methods, with undersampling often yielding higher F1 scores, whereas Support Vector Machine models showed reduced classification performance. These findings highlight the importance of selecting class-balancing strategies based on dataset size, analytical platform, and ML algorithm in metabolomics studies.

Alternaria fungi produce various structurally diverse mycotoxins, several of which exhibit immunomodulatory properties. Among these, alternariol monomethyl ether (AME), alternariol (AOH), alterperylenol (ALTP), altertoxin I (ATX-I), and altersetin (AST) have been reported to suppress lipopolysaccharide (LPS)-induced inflammatory responses. However, the precise molecular mechanisms underlying these effects remain unclear. The present study aimed to elucidate how these selected Alternaria mycotoxins (0.1-50 M) target the NF-{kappa}B signaling pathway in THP-1 monocytes. Key components of the NF-{kappa}B cascade were analyzed by immunofluorescence microscopy, Western blotting and qRT-PCR. Nuclear translocation of NF-{kappa}B p65 and its phosphorylated form (p- NF-{kappa}B p65) was assessed by Western blot, while cytokine responses were determined at transcript (qRT-PCR) and protein (ELISA) levels. Moreover, in silico docking analyses were performed to investigate potential interactions of the toxins with IKK{beta}, and receptor-mediated crosstalk was studied using the glucocorticoid receptor (GR) antagonist RU486. Co-treatment with RU486 attenuated the immunosuppressive effects of 1 and 5 M AOH, indicating partial involvement of GR-dependent mechanisms. AME, AOH, ALTP, ATX-I, and AST increased total I{kappa}B levels while reducing its phosphorylated form. Additionally, AST and ALTP decreased the protein levels of Toll-like receptor 4 (TLR4), the I{kappa}B kinase (IKK) complex, NF-{kappa}B p65, and p- NF-{kappa}B p65. While AOH (5 M) and AST (25 M) reduced nuclear translocation of p65 and p-p65, ALTP (2 M) enhanced nuclear localization despite decreasing cytokine expression. Together, these findings suggest toxin-specific interference at multiple regulatory levels of NF-{kappa}B signaling and provide novel mechanistic insight into the immunomodulatory effects of Alternaria mycotoxins.

Greenspace has been associated with a wide range of health outcomes and conditions related to functional limitation and disability. Yet less is known about how the spatial morphology of greenspace relates to disability prevalence across different stages of the life course. This study examines associations between greenspace morphology and disability prevalence among children, working-age adults, and older adults in urban census tracts across the contiguous United States. Using national land-cover data, we quantified morphological metrics at the census-tract level, including greenspace percentage, density, mean size, connectedness, shape complexity, inter-greenspace distance, and diversity. These indicators were linked with age-specific disability prevalence obtained from the American Community Survey. Spatial lag regression models were used to account for spatial dependence while adjusting for socio-demographic and contextual characteristics. Across age groups, higher greenspace percentage was consistently associated with lower disability prevalence (children: {beta} = -0.081, 95% CI: -0.096 to -0.066; adults: {beta} = -0.804, -0.858 to -0.750; older adults: {beta} = -1.132, -1.250 to -1.013). Among children, patch density ({beta} = -0.045, -0.061 to -0.029), mean patch area ({beta} = -0.029, -0.040 to -0.018), connectedness ({beta} = -0.051, -0.069 to -0.032), diversity ({beta} = -0.036, -0.051 to -0.020), and inter-greenspace distance ({beta} = 0.056, 0.039 to 0.073) were all associated with disability prevalence, whereas shape complexity was not ({beta} = 0.004, -0.010 to 0.018). Among working-age adults, associations were observed for mean area ({beta} = -0.023, -0.090 to -0.002), connectedness ({beta} = -0.127, -0.243 to -0.011), shape complexity ({beta} = -0.123, -0.174 to -0.072), diversity ({beta} = -0.146, -0.201 to -0.091), and inter-greenspace distance ({beta} = 0.151, 0.059 to 0.242), whereas patch density was not significantly associated with disability prevalence ({beta} = -0.013, -0.048 to 0.022). In older adults, all examined greenspace morphology metrics showed significant associations with disability prevalence, including patch density ({beta} = -0.445, -0.842 to -0.049), diversity ({beta} = -0.126, -0.188 to -0.065), and inter-greenspace distance ({beta} = 0.455, 0.409 to 0.501). Overall, the findings suggest that higher greenspace percentage, larger patch size, greater connectedness, greater diversity, and more spatially clustered greenspace distributions are associated with lower disability prevalence across the life course, although the strength and consistency of these associations varied across age groups. The study provides national-scale evidence for incorporating greenspace morphology into urban planning and public health strategies to support more inclusive and health-supportive urban environments.

Extrahepatic delivery of lipid nanoparticles (LNPs) to non-phagocytic cells is a major challenge, with the leading strategy involving surface functionalization with target-specific monoclonal antibody (mAb) ligands. We investigate the stability of mAb-conjugated LNPs using two anchoring systems: the commonly used DSPE-PEG2kDa-maleimide and a block copolymer, PCL5kDa-b-PEG2kDa -maleimide, with the hypothesis that conjugation to a 150,000 Da antibody could overwhelm the relatively small ~600 Da aliphatic anchor on the PEG-lipid in vivo. Shedding of the mAB would compromise targeting. Conjugation integrity following IV injection was assessed by tagging LNPs and mAbs with metal ion tracers that could be quantified by ICP-MS. Results show that DSPE-PEG-mAb rapidly (within 1h) dissociates from LNPs in blood, leading to accelerated LNP clearance. In contrast, mAbs conjugated using PCL-b-PEG remained stably associated with the LNP over the 24h circulation and clearance of the construct. Results are connected to a thermodynamic model that reproduces experimental findings for PEG-anchor(-mAb) shedding in vitro and in vivo. This study identifies anchoring strength as a critical, unconsidered parameter for in vivo performance when conjugating mAbs to LNPs for extrahepatic delivery.