Long-term Exposure Research Articles

Long-Term Particulate Matter Exposure May Increase Risk of Chronic Rhinosinusitis WIth Nasal Polyposis: Results from an Exposure-Matched Study.

Particulate matter ⩽2.5µm in diameter (PM2.5) and its role in chronic rhinosinusitis (CRS) pathogenesis have gained heightened attention. We previously demonstrated that PM2.5 exposure may bias the nasal mucosa in CRS toward a Type 2 inflammatory pathway. However, there are limited data comparing cytokine changes in CRS sinonasal tissue to non-CRS patients as it relates to PM2.5 exposure. We hypothesized that long-term exposure preferentially increases the risk of manifesting CRS with nasal polyposis (CRSwNP). We performed a retrospective analysis of 376 patients (308 CRS, 68 controls) who underwent endoscopic sinus or skull base surgery. A spatiotemporal machine-learning model estimated daily PM2.5 levels for 1 year prior to each patient's surgery date. Cytokines were quantified using a multiplex flow cytometric bead assay and compared to estimated PM2.5 exposure using Spearman correlation and multivariate regression. Patients with high and low 12-month PM2.5 exposures were matched across age, sex, income, and rurality using a nearest neighbor algorithm. Multivariate adjusted logistic regression was used to estimate the odds of CRS based on PM2.5 exposure. Reduced IL-10 levels were associated with higher PM2.5 exposures in control patients (β=-0.735, p=0.0196). In exposure-matched logistic regression analysis, high 12-month PM2.5 exposure was an independent predictor of CRSwNP (β=1.97, OR: 7.22, p=0.0001) after adjustment for age, income, rurality, and comorbid asthma/allergic rhinitis. A similar relationship was not identified for CRSsNP. PM2.5 exposure is associated with reduced IL-10 in control patients compared to CRS and may increase odds of CRSwNP development.

Abstract 599: Oligomeric proanthocyanidins overcome Lenvatinib resistance by targeting ITGA3 and EGFR-AKT pathways in hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) is the third most common cancer worldwide and is often diagnosed at an advanced stage, with chemotherapy often being the treatment of choice. Lenvatinib, a multi-targeted tyrosine kinase inhibitor, is widely used as a first-line therapy for advanced HCC following the REFLECT trial, demonstrating its non-inferiority to Sorafenib in overall survival. Additionally, combination therapies with immune checkpoint inhibitors or transarterial chemoembolization have shown promising results, with clinical studies indicating improved overall survival compared to monotherapies. However, frequent resistance to Lenvatinib significantly limits its clinical efficacy, necessitating novel strategies to address this challenge. Various pathways have been reported for the mechanisms of Lenvatinib resistance, including activation of EGFR, changes in the immune microenvironment, and activation of tumor stem cells. Oligomeric proanthocyanidins (OPCs), natural polyphenols with broad-spectrum anticancer properties, may enhance Lenvatinib’s efficacy by targeting these resistance pathways. This study aims to elucidate the mechanisms of Lenvatinib resistance and evaluate the potential of OPCs to overcome resistance in HCC. Methods: Lenvatinib-resistant Huh-7 and PLC-PRF-5 cell lines were generated through long-term exposure to increasing concentrations of Lenvatinib. We performed a series of cell culture experiments to evaluate the synergistic anticancer effect of the combination of Lenvatinib and OPCs in Lenvatinib-resistant cell lines. By performing genome-wide transcriptomic profiling, we identified specific growth-signaling pathways targeted by the combined treatment and validated these findings in cell lines. Results: The combination therapy of Lenvatinib and OPCs yielded promising results, significantly suppressing cell proliferation, invasion, and spheroid formation in Lenvatinib-resistant HCC cells. Transcriptomic analysis revealed that ITGA3 is a critical factor in Lenvatinib resistance, and its upregulation is associated with poor prognosis in HCC patients. Furthermore, high ITGA3 expression in resistant cells was found to promote activation of the EGFR-AKT pathway and enhance resistance to anoikis, contributing to Lenvatinib resistance. Molecular analyses demonstrated that this combination therapy effectively suppresses the ITGA3, EGFR-AKT pathway, thereby overcoming Lenvatinib resistance and supporting the promising results of this treatment. Conclusion: This study identifies OPCs as a promising therapeutic agent for overcoming Lenvatinib resistance by targeting ITGA3 and the EGFR-AKT pathways. The results emphasize the potential benefits of combining OPCs with Lenvatinib to enhance therapeutic efficacy and improve outcomes in Lenvatinib-resistant HCC. Citation Format: Takayuki Noma, Yuan Li, Yuma Wada, Katsuki Miyazaki, Yuji Morine, Mitsuo Shimada, Ajay Goel. Oligomeric proanthocyanidins overcome Lenvatinib resistance by targeting ITGA3 and EGFR-AKT pathways in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 599.

Abstract 5643: Aryl hydrocarbon receptor agonist ZSTK3744 overcomes chemotherapy resistance in TNBC

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis compared with other subtypes. Due to the lack of therapeutic targets, such as hormone receptors and human epidermal growth factor receptor 2, systemic chemotherapy remains the primary treatment option for TNBC. However, chemotherapy has limited benefits and some patients acquire resistance, further complicating treatment. New therapeutic approaches are urgently needed to overcome chemotherapy resistance in TNBC. ZSTK3744 is an aryl hydrocarbon receptor agonist developed as a novel therapeutic candidate for TNBC. ZSTK3744 has shown inhibitory effects on the proliferation of various cancer cell lines, including TNBC cell lines, in vitro. Moreover, it suppressed tumor growth in TNBC xenograft models. In this study, we evaluated the effects of ZSTK3744 on chemotherapy-resistant TNBC cells. Chemotherapy-resistant MDA-MB-468 cells, derived from TNBC, were developed through long-term exposure to adriamycin or paclitaxel. Compared to wild-type cells, the anti-tumor effects of adriamycin, paclitaxel, and eribulin were weakened in these resistant cells; however, ZSTK3744 maintained its efficacy. Transcriptome analysis was conducted to elucidate the mechanism of chemotherapy resistance, revealing alterations in several resistance-associated genes. In particular, upregulation of the ATP-binding cassette transporter 1 gene (ABCB1) was commonly observed in these cells. The anti-tumor effects of adriamycin, paclitaxel, and eribulin were reduced in cells with high ABCB1 expression, whereas those of ZSTK3744 were unaffected. Moreover, ZSTK3744 significantly inhibited tumor growth in xenograft models implanted with adriamycin-resistant MDA-MB-468 cells, showing a higher potency than eribulin. ZSTK3744 is a promising agent for overcoming chemotherapy-resistance in TNBC. Citation Format: Takahiro Ohashi, Kayoko Kawai-Asami, Sayuri Terada, Kotomi Akatsuka, Yuko Nagata, Shinsuke Hiramoto, Tsubasa Nagasaki, Eika Higashi, Ryuichiro Ohshita, Keiko Fukushima. Aryl hydrocarbon receptor agonist ZSTK3744 overcomes chemotherapy resistance in TNBC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5643.

Abstract 1392: Mechanism of chemoresistance in esophageal squamous cell carcinoma based on mitochondrial DNA copy number

Abstract Epithelial-to-mesenchymal transition (EMT) has been reported to be associated with metastasis and resistance to therapy in various carcinomas. However, the mechanism of EMT induction and its regulation remain unresolved. Esophageal cancer is one of the most difficult-to-treat cancers that metastasize and are refractory to therapy. In this study, we focused on mitochondrial DNA to elucidate the mechanism of EMT induction in esophageal cancer and to search for therapeutic targets. We established a resistant strain (TE11-R) by long-term exposure of an esophageal cancer cell line (TE11) to chemotherapy (CDDP), and found that TE11-R acquired mesenchymal characteristics. We also observed that the mtDNA copy number was decreased in TE11-R. Next, we established ESCC with reduced mtDNA copy number (TE11-shT) by knockdown of mitochondrial transcription factor A (sh-TFAM). First, mtDNA copy number was reduced to 60% in TE11-shT. Complex IV activity and membrane potential (MMP) were reduced in TE11-shT compared to control TE11. Next, exposure of TE11 to depolarizing agents (CCCP) decreased expression of epithelial markers (CDH1) and increased expression of mesenchymal markers (CDH2, Vimentin, ZEB1) by qPCR and WB. Exposure of TE11-shT and CCCP to DNMT inhibitors increased expression of E-cadherin, decreased expression of N-cadherin and Vimentin, and improved CDDP sensitivity. and CDDP sensitivity were observed. Decreased mtDNA copy number in esophageal squamous cell carcinoma induced EMT via increased DNMT expression, suggesting that DNMT inhibitors may be therapeutic targets for treatment-resistant esophageal cancer cells. Citation Format: Koji Tanaka, Yuto Kubo, Kotaro Yamashita, Tomoki Makino, Tsuyoshi Takahashi, Yukinori Kurokawa, Kiyokazu Nakajima, Hidetoshi Eguchi, Yuichiro Doki. Mechanism of chemoresistance in esophageal squamous cell carcinoma based on mitochondrial DNA copy number [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1392.

Abstract 1727: Sequencing MEK inhibitor therapy after tovorafenib in BRAF fusion-driven cancers: Preclinical evidence of sustained tumor regression

Abstract BRAF fusions and BRAF V600 point mutations are oncogenic drivers found in many pediatric and adult cancers, and constitutively activate the downstream MAPK pathway (Jones et al 2009, Yaeger and Corcoran 2019). Tovorafenib is the first and only type II RAF inhibitor approved for the treatment of BRAF-altered relapsed/refractory pediatric low-grade glioma (pLGG) in patients ≥ 6 months of age. In the ongoing ph 2 study, FIREFLY-1, tovorafenib demonstrated robust clinical activity in patients with BRAF-altered pLGG who progressed on systemic therapy, which may have included MEK inhibitors (Kilburn et al 2024). This preclinical study evaluated if tovorafenib-sensitive BRAF fusion tumors that have regrown during a drug holiday would also respond to a MEK inhibitor. The potential emergence of resistance with long-term exposure to tovorafenib was also explored. Due to the lack of availability of pLGG KIAA1549::BRAF fusion (the most commonly occurring BRAF fusion in pLGG) PDX models, in vivo experiments were conducted using a AGK::BRAF fusion melanoma PDX model. Mice bearing AGK::BRAF fusion melanoma tumors were treated with a clinically relevant dose (25 mg/kg oral, once daily) of tovorafenib for 14 days or until complete regression of tumors was observed. An off-treatment period was then initiated, during which tumors regrew. Once individual tumors regrew to 100-200 mm3 size (within approximately 2 weeks), mice were treated for 14 days with a MEK inhibitor (trametinib; 0.3 mg/kg oral, once daily), or tovorafenib was resumed. Complete tumor regression was observed in all tumors in response to either trametinib or tovorafenib retreatment. Further evaluation of other MEK inhibitors and different dosing sequences of MAPK inhibitors is ongoing. In addition, the efficacy of tovorafenib in a CDC42SE2::BRAF anaplastic pleomorphic xanthoastrocytoma (APXA) PDX model is also being investigated. To explore potential mechanisms of acquired resistance, we also evaluated whether resistant tumors would emerge with continuous dosing of tovorafenib. Tovorafenib was administered (25 mg/kg oral, once daily) to mice bearing AGK::BRAF fusion tumors for 90 days. Over the entire course of treatment, significant tumor regression was maintained with no emergent tumors. In conclusion, our study provides evidence for the efficacy of sequencing MEK inhibitor treatment after tovorafenib in a PDX model of AGK::BRAF fusion melanoma. Furthermore, long-term efficacy was maintained with continuous dosing of tovorafenib in vivo, with no signs of emerging resistance preclinically, supporting the hypothesis that acquired resistance may be less common in BRAF fusion driven tumors treated with tovorafenib. Citation Format: Samantha Perino, Yujin Wang, Shubhra Rastogi, Nur P. Damayanti, Karen E. Pollok, Sandya Govinda Raju, Mark W. Kieran, Samuel C. Blackman, Eleni Venetsanakos. Sequencing MEK inhibitor therapy after tovorafenib in BRAF fusion-driven cancers: Preclinical evidence of sustained tumor regression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1727.

Abstract 4003: Improved drug screening and resistance monitoring using cancer organoids derived from dissociated tumor cells and circulating tumor cells

Abstract Cancer is a complicated disease, and despite recent breakthroughs in cancer treatment, cancer remains the second leading cause of death globally, with metastatic cancers responsible for the large majority. To develop effective cancer drugs, we need reliable in vitro models that represent cancers accurately, particularly for metastatic cancers. However, current experimental models of human cancers in vitro face several limitations. Well-established cell lines typically emerged from long-term exposure to simple tissue culture conditions, while genomic and epigenetic instability contribute to their drift away from the characteristics of the original tumors. Because of the significant heterogeneity both within each tumor and within each type of cancer, cell lines fail to represent the diversity of the disease. Even using a very large number of cell lines still restricts the results to cancers whose cells grow on plastic in relatively uncomplex media formulations. Aiming to overcome these limitations, we are leveraging a novel system for culturing tumor organoids. We culture tumor organoids from dissociated tumor cells (DTCs) from primary tumors, or circulating tumor cells (CTCs) from the blood of patients with solid tumors, in our proprietary culture platform. We have successfully cultured a wide range of DTC and CTC samples into tumor organoids, including samples from breast, colon, renal, lung, pancreatic, and prostate cancers, and we continue to add to the list. The successful expansion of these samples enables us to overcome the limited availability of such material and to apply methods typically reserved for cell line-based drug screening. We tested the drug sensitivity of these organoids to standard-of-care chemotherapeutics and other approved anticancer drugs, by cell viability assay. We also monitored organoid morphology longitudinally by brightfield microscopy during the treatment period. To evaluate drug resistance, we plated tumor organoids into Corning Elplasia plates, separating organoids into individual microcavities and enabling longitudinal tracking of each organoid throughout treatment. We continued culturing the surviving drug-resistant organoids after the treatment period and evaluated their changes in phenotype, morphology, mutation status, and gene expression. To characterize the resistance of individual organoids, we tested whether single-organoid RNA-Seq could provide more useful insights than bulk RNA-Seq. DTC- and CTC-derived organoids typically exhibit differing sensitivities in our drug sensitivity screening. Since CTC-derived organoids resemble metastatic cancers, this platform enables the evaluation of anti-metastatic cancer drug efficacy, representing a major improvement over the current system. Citation Format: Yi-chun Han, David Hsieh, Shian-Jiun (SJ) Shih. Improved drug screening and resistance monitoring using cancer organoids derived from dissociated tumor cells and circulating tumor cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4003.

Characterization of Biobased Polymers at the Gas-Solid Interface─Analysis of Surface and Bulk Properties during Artificial Degradation.

Accurately assessing the interfacial composition and reactivity of (bio)polymers under controlled but environmentally relevant conditions remains challenging. This study explores the evolution of surface functionalities of novel polyesters Poly(Butylene Xylose) (PBX) and Poly(Alkyl Xylose Amide) (PAXA) under artificial degradation conditions. Employing a Knudsen Flow Reactor (KFR) and a gas-titration approach, we systematically analyze the chemical transformations occurring at the polymer's solid-gas interface. Both polymers are derived from the same functionalized lignocellulosic sugar building block, Diglyoxylic Acid Xylose (DGAX). Virgin (V), long-term UV (UV), and short-term Ozone (O3) exposures induce specific but differing alterations in molecular integrity and surface reactivity, resulting in notable shifts in material properties and polymer structure. Contrary to the assumption that degradation increases specific surface area (SSA) and reactivity, our results reveal cases where the SSA decreases, with reactivity either increasing or decreasing based on the reactive groups available at the interface. Both polymers exhibited increased water affinity, acidification, and ozone reactivity following UV exposure. Interfacial reactivity, assessed with trifluoroacetic acid, hydroxylamine, and nitrogen dioxide, increased for PBXUV but decreased for PAXAUV. Surface hydroxyl groups in PAXA reduced 5-fold under short-term ozone and long-term UV exposure, while bulk transport kinetics of hydroxylamine altered with long-term degradation, though ozone exposure left transport mechanisms unaffected. This combined interfacial and bulk analysis approach advances our understanding of (bio)plastic degradation. It examines the role of degraded polymers as potentially more or less reactive vectors for chemicals and organisms upon environmental release while also demonstrating that polymer degradation initiates significantly earlier than previously assumed.

Assessment of disease burden and mortality attributable to air pollutants in northwestern Iran using the AirQ+ software

It is well known that one of the main causes of mortality and reduced life expectancy is air pollution, which carries the highest burden of diseases attributed to environmental factors. The poor air quality in Iranian cities leads to a wide range of acute and chronic health effects. This study estimates the natural deaths, ALRI, COPD, lung cancer, IHD, and strokes caused by air pollutants in Bukan, a southern city in West Azerbaijan Province, from 2011 to 2019. Population data was obtained from government organizations, and pollutant data for 2011–2019 was collected from the Bukan Environmental Protection Organization. Analyses were performed using Excel, and the data was subsequently entered into the WHO’s AirQ+ model to extract the results. The study found that long-term exposure to PM10, PM2.5, NO2, and O3 resulted in an estimated 316, 241, 14, and 52 deaths, respectively. By comparing the air quality over the 8-year period, it was determined that the air quality in Bukan city is not in good condition, with particulate matter levels exceeding relevant standards. Given the increasing trend of air pollution and associated health impacts, it is essential to implement effective control policies to improve the city’s air quality. This information provides a crucial step for city managers, policymakers, and health officials to mitigate the health effects caused by air pollution.

Variability in microplastic abundance, bisphenol A contamination, antioxidant properties, and health risks associated with vegetable consumption

BackgroundPlastic pollution, particularly microplastics (MPs) and toxic additives such as bisphenol A (BPA), endangers human health. Therefore, their routes in the environment need to be investigated. This study investigated microplastic (MPs) abundance, bisphenol A (BPA) levels, and antioxidant activity (AA) in three commonly consumed vegetables—green amaranth, jute mallow, and spinach sourced from two markets in Osogbo, southwestern Nigeria. Microscopic technique was used to determine MP abundance, shapes, and colours. High-performance Liquid Chromatography (HPLC) was used to analyse BPA contents while 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was used to measure AA. A hazard index (HI) and estimated dietary intakes (EDIs) were used to estimate the associated risks and food safety concerns with MP and BPA in vegetables.ResultsIn this study, MP abundance in shoots ranged from 4.00 ± 0.50 to 7.67 ± 1.04 particles/g and in roots from 5.33 ± 1.53 to 18.00 ± 6.93 particles/g in spinach and green amaranth, respectively, indicating subsoil contamination. Three shapes (fragment, fibre, and irregular) and five colours (transparent, white, yellow, black, and brown) were detected, with fragment shape and transparent colour dominating. Fourier Transform Infrared spectroscopic (FTIR) analysis revealed a predominance of polyethylene, polypropylene, polyethylene terephthalate, polyvinyl chloride, and polyamide microplastics. The BPA ranged from 5.55 ± 0.56 to 6.65 ± 0.00 μg/g while AA ranged from 40.67 ± 6.79 to 72.55 ± 4.03%. A regression analysis and principal component analysis (PCA) were used to identify the relationship among the factors (MPs, BPA, and AA). It is suggested that high levels of MPs and BPA negatively impacted vegetable quality as they are associated with environmental contamination. Contrastingly, AA had a significant positive correlation with vegetable quality. Both EDIs and HI of MPs and BPA were < 1, indicating no significant risk associated with BPA exposure from their consumption.ConclusionThis study highlights the potential health risks of MPs and associated BPA contamination in vegetables. The estimated dietary intake and hazard index suggest no immediate health risks, but long-term exposure remains a concern. MPs and BPA in commonly consumed vegetables warrant stricter monitoring of agricultural soil and irrigation water sources. Microplastic exposure in food crops can be reduced with policies that regulate plastic waste disposal and promote sustainable farming practices.

Repeated treatment with JWH-018 progressively increases motor activity and aggressiveness in male mice: involvement of CB1 cannabinoid and D1/D2 dopaminergic receptors.

Repeated treatment with JWH-018 progressively increases motor activity and aggressiveness in male mice: involvement of CB1 cannabinoid and D1/D2 dopaminergic receptors.

Mechanisms by which sevoflurane affects cognitive function in aged marmosets and mice: up-regulation of FKBP5 expression in brain microglia.

JOURNAL/mgres/04.03/01612956-990000000-00062/figure1/v/2025-04-17T161621Z/r/image-tiff Inhalation anesthetics may trigger the hypothalamic-pituitary-adrenal axis. FK-506 binding protein (FKBP5) is a critical regulator of the hypothalamic- pituitary-adrenal axis and has been implicated in postoperative cognitive dysfunction. However, how inhalation anesthetics affect the expression and function of FKBP5 in the brain is unclear. We employed single-nucleus RNA sequencing to delineate the hippocampal transcriptomic profiles of the brains of aged marmosets and mice after sevoflurane anesthesia. The results of single-nucleus RNA sequencing revealed that long-term exposure (6 hours) to sevoflurane significantly increased FKBP5 expression in the hippocampus of aged marmosets and mice, especially in microglia. Western blot assay also verified the above results. The Barnes maze test showed that, compared with heterozygous control mice, microglia-specific FKBP5 conditional knockout mice exhibited improved neurocognitive function after sevoflurane/surgery. Transcriptome sequencing analysis was performed on the brains of microglia-specific FKBP5 conditional knockout mice and heterozygous mice after sevoflurane/surgery and further revealed that FKBP5 was related mainly to inflammatory signaling pathways. Therefore, these findings indicate that long-term exposure to sevoflurane increases FKBP5 expression in the hippocampus of aged marmosets and mice, which thereby affects inflammatory signaling pathways and leads to postoperative cognitive dysfunction.

Enhancing the Adhesion of Polyaniline on Steel Substrates Without a Binding Agent: Evaluated by ASTM D 3359 Tape Test and Sodium Chloride (NaCl) Exposure

This study presents a method for enhancing the adhesion of chemically synthesized polyaniline on steel substrates without the need for a binding agent. Hydrochloric acid (HCl) was used in the synthesis of polyaniline. The experiment details the in situ chemical synthesis of polyaniline and its application as a coating on steel surfaces using an air spray technique. Pre-surface treatment, including cleaning and sanding, was performed on the steel substrates prior to coating. Following the application of the polyaniline coating, heat treatment was applied, where the coating was heated to 350 °F for 3 h after it was fully dried. The adhesion properties of the coating were evaluated using the ASTM D 3359 adhesive tape test, along with short- and long-term exposure to 3.5% sodium chloride (NaCl) solution. Additional analysis, including SEM, XPS, XRD, and coating thickness measurements, demonstrates the effectiveness of polyaniline in enhancing adhesion on steel substrates.

Deriving exposure route-specific cancer slope factors of carcinogenic chemicals via PBK modeling.

Carcinogenic chemicals entering the body via different exposure routes result in varying internal doses and thus influence the tumors development. The internal doses can be quantified using biotransfer factors (BTF) simulated by the physiologically based kinetic (PBK) model. This study proposed a modeling method to analyze the quantitative relationships between BTF and cancer slope factors (CSFs). When the CSF for one exposure route is known, the CSF values for the other two routes can be derived using the relationships. A total of 45 carcinogenic chemicals were selected, and their oral CSF (CSForal) and BTF values were collected for analysis. The results demonstrated that route-specific CSFs of chemicals can be different due to their physicochemical properties. In addition, the derived route-specific CSFs are further utilized to conduct a comprehensive cancer risk assessment. The results revealed that cancer risk caused by most environmental chemical exposure exceeded 1×10-6, suggesting that long-term exposure to chemicals would pose certain human cancer risks. These findings highlight the importance of exposure route-specific CSFs for accurate cancer risk assessment and provide a scientific reference for environmental agencies to refine the risk assessment system.

Durable One-Dimensional Liquid-Infused Surface for Practical Dropwise Condensation Enhancement.

Suitable contact angle (CA) and contact angle hysteresis (CAH) of liquid-infused surfaces (LISs) make them promising candidates for condensation enhancement. However, their practical application encounters restrictions arising from issues such as low durability, unscalability, and high cost. In this study, aluminum covered with silicone oils of various viscosities and decamethylcyclopentasiloxane (D5) is exposed to ultraviolet (UV) light for two different periods to produce a durable, yet low-cost, 1-D LIS without the use of hazardous materials. For short-term exposure, 10 h of radiation is utilized, whereas long-term exposure depends on the gelation time of the lubricants. Tests reveal that all lubricants are chemically attached to the substrate, possessing a CA of >100° and CAH of lower than 10°. Furthermore, the fabricated samples can reduce the corrosion current density by up to 2 orders of magnitude with respect to bare aluminum. The condensation test reveals that the surface, covered with 5 cSt silicone oil that is exposed to UV light for 10 h, enhances the condensed water by 29%, 38%, and 39% at subcooling temperatures of 14.5, 10, and 5.5 K compared to bare aluminum, respectively. Additionally, compared with the literature, the durability of the fabricated LIS is improved by 350%.

Perfluorooctane sulfonic acid: a possible risk factor of endothelial dysfunction based on in silico and in vitro studies.

Perfluorooctane sulfonic acid (PFOS) is a fluorinated chemical utilized in a variety of industrial and household products. PFOS has been detected in human serum and is associated with multiple human adverse health effects. Epidemiological evidence has linked PFOS exposure to endothelial dysfunction, which is a key contributor to atherosclerosis. However, the underlying mechanisms of PFOS-induced endothelial dysfunction associated atherosclerosis has not been investigated. In the present study, human microvascular endothelial cells (HMEC-1) exposed to PFOS (15μM) for 72h, mimicking long-term exposure. We further employed integrated RNA-sequencing (RNA-seq) and transcriptomic analysis to identify differentially expressed genes (DEGs) for biological alterations: gene ontology (GO), pathway enrichment analysis (KEGG), protein-protein interaction network and modular clustering analysis. Furthermore, the Metascape database was used for disease association, tissue specificity, and transcription factor analysis. Hub genes were verified using atherosclerosis patient data sets from the GEO dataset. Alteration of hub genes in patients was then validated using immunoblotting and ELISA. Our results revealed that PFOS altered amino acid biosynthesis, lipid metabolism and induced the ER-stress response through the HRI/eIF2α/ATF4 pathway, leading to endothelial dysfunction. Interestingly, we found that PFOS induced inflammation by increasing COX-2, ICAM-1 and IL-6 expression through NF-κB and JAK2/STAT3 pathway in endothelial cells. Moreover, up-regulated C/EBPβ and ATF4 were observed in both patients and PFOS-exposed endothelium, which may use as an early biomarker and may have a potential role in PFOS-induced endothelial dysfunction. These findings provide novel insight into the underlying molecular mechanisms of PFOS-induced endothelial dysfunction associated with atherosclerosis.

DETERMINATION OF HEAVY METALS CONCENTRATION IN FISH SPECIES FROM DADIN KOWA DAM CONSUMED IN SOME PARTS OF GOMBE STATE, NORTHEASTERN NIGERIA AND ITS HEALTH EFFECTS

Despite increasing in industrial and agricultural activities near Dadin Kowa Dam, limited data exist on heavy metal contamination in its aquatic ecosystem. This study investigates metal concentration in commonly consumed fish species in northern parts of Nigeria and many parts of Africa to assess potential health risks. Heavy metals in fish originate from industrial discharge, agricultural runoff, and natural geological processes, necessitating continuous monitoring. Chronic exposure to Pb, Cd, As, Fe, Cu, and Ni is linked to neurological damage, renal failure, and carcinogenic effects, making their presence in food sources a serious concern. AAS analysis was performed using certified reference materials, and calibration was validated with standard solutions to ensure accuracy. The planet catfish was found to have high levels of lead (0.0237 mg/100g), while Cadmium contents in Red-tailed Synodontis were alarming (0.0560 mg/100g), beyond safety limits and potentially harmful to health. The greatest arsenic level was found in African Cat Fish (0.0655 mg/100g), which suggests that long-term exposure should be avoided. ANOVA results (p &lt; 0.05) indicate significant variation in heavy metal accumulation between species, identifying Planet Catfish and Red-tailed Synodontis as the most contaminated. To minimize exposure risks, regular monitoring programs, public health advisories, and dietary guidelines on fish consumption should be implemented. Findings are compared against WHO/FAO (2021) guidelines for permissible heavy metal concentrations in fish.

Association between air quality and neurodegenerative diseases in River Sacco Valley: A retrospective cohort study in Latium, central Italy.

Association between air quality and neurodegenerative diseases in River Sacco Valley: A retrospective cohort study in Latium, central Italy.

The association between multiple environmental exposures and symptoms of generalized anxiety disorder in a prospective, U.S.-based cohort study.

Emerging evidence has implicated built and natural environmental exposures in the etiology and exacerbation of anxiety symptoms. Our objective was to assess individual and joint associations between neighborhood socioeconomic status (nSES), walkability, greenness, fine particulate matter (PM2.5), nitrogen dioxide (NO2), and temperature and generalized anxiety disorder (GAD) symptoms. We included 81,897 participants of the Nurses' Health Study II. GAD symptoms were measured in 2013 and 2017 using the 7-item Generalized Anxiety Disorder scale (GAD-7). Walkability and nSES z-scores were calculated at the Census tract level. Normalized Difference Vegetation Index (NDVI) summer and annual average greenness at 270m and 1230m buffer sizes, and spatiotemporal models predicted one-, three-, and twelve-month averages of PM2.5, NO2, and temperature were calculated at the residence. Longitudinal logistic and generalized estimating equations (GEE) models estimated odds ratios and 95% confidence intervals for clinically relevant GAD symptoms (GAD-7 ≥ 5 points). We assessed effect modification by nSES, summer NDVI (1230m), and select covariates. We employed quantile g-computation to more directly assess the association between environmental exposure mixtures and GAD symptoms. In single exposure models, summer NDVI (e.g., for 1230m, OR: 0.96, 95% CI: 0.94, 0.98), NO2 (e.g., for twelve-month average NO2, OR: 1.03, 95% CI: 1.01, 1.04), twelve-month average temperature (OR: 1.05, 95% CI: 1.03, 1.07, and walkability (OR: 1.02, 95% CI: 1.01, 1.03) were associated with GAD symptoms. In the joint exposure model, nSES (OR: 0.96, 95% CI: 0.95, 0.98) and summer NDVI were associated (OR: 0.92, 95% CI: 0.88, 0.96); all other associations were attenuated. Associations with summer NDVI (1230m), temperature, and NO2 were modified by nSES, with stronger associations in socioeconomically deprived areas. In this population, higher levels of summer greenness and nSES may be protectively associated with GAD symptoms, while medium- and long-term NO2 exposure, long-term temperature, and walkability are adversely associated with GAD symptoms. Socioeconomically deprived areas may bear additional risks. The results of the quantile g-computation analysis suggest that environmental exposures may act antagonistically with one another in relation to GAD symptoms. https://doi.org/10.1289/EHP14458.

Long-term exposure to nitrate and trihalomethanes in drinking-water and gastric cancer: A Multicase-Control Study in Spain (MCC-Spain).

Disinfection byproducts and N-nitroso compounds (NOC) formed endogenously after nitrate ingestion have been shown to be carcinogenic in animal studies, but epidemiological evidence is limited, especially in relation to gastric cancer. We evaluated the association between drinking-water exposure to nitrate and trihalomethanes (THMs) and gastric cancer in the Multicase-Control Study conducted in Spain (MCC-Spain). In 2008-2013, 254 hospital-based incident gastric cancer cases and 2,365 population-based controls were recruited, providing information on residential histories and type of water consumed. Adult lifetime average nitrate and THM levels in residences from age 18 until 2 years before the interview were estimated and linked with water consumption information to calculate waterborne ingested nitrate, brominated (Br)-THMs and chloroform. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression, with adjustment for potential confounders. We assessed the effect modification by factors influencing endogenous NOC formation. Median (P25-P75) lifetime waterborne ingested nitrate (mg/day), Br-THMs (μg/day) and chloroform (μg/day) were 2.7 (1.4-5.6), 3.8 (1.5-8.1), and 12.2 (4.0-23.7), respectively, in cases; and 3.8 (1.8-8.5), 5.7 (2.6-19.2) and 12.9 (4.6-24.5) in controls. Adjusted OR (95%CI) for gastric cancer comparing nitrate intake > vs. ≤ 9.7 mg/day (80th percentile) was 1.42 (0.88-2.29). This association was more pronounced among participants with low consumption of vegetables (2.24 (1.02-4.91)), vitamin C (2.10 (0.94-4.71)), and vitamin E (2.81 (1.16-6.78)), and among those with high consumption of alcohol (2.78 (0.98-7.93) or processed meat (1.91 (0.97-3.75). When stratified by age, the association only remained in the >65 years group (median 73 years). OR for gastric cancer comparing Br-THM ingestion ≥ vs. < 80th percentile was 0.65 (0.33-1.28) and for chloroform was 1.36 (0.87-2.14). Comparable ORs were found for residential concentrations. Long-term waterborne nitrate exposure below regulatory limits may increase gastric cancer risk among older adults and in those with poor dietary patterns. These findings need to be confirmed by cohort studies with larger sample sizes.. https://doi.org/10.1289/EHP15039.

Ultralight and Flame-Retardant Nanofiber/Aerogel Microfiber Sponges with Dual-Network Structures for Warmth Retention.

Long-term exposure to cold conditions can cause damage to the body, which makes cold prevention equipment urgently needed. However, the most commonly used fibrous warmth retention materials have drawbacks of heavy weight, poor mechanical properties, flammability, and inefficient thermal insulating performance. Herein, we propose a simple and feasible strategy to prepare nanofiber/aerogel microfiber sponges (NAMS) with dual-network structures for warmth retention by direct electrospinning. The aerogel fibers are prepared by regulating the phase separation behavior of the jet, while flexible nanofibers are introduced between the aerogel fibers to construct dual-network structures in the sponge. The obtained NAMS is lightweight (3.44 mg cm-3) and exhibits robust mechanical properties (almost no plastic deformation after enduring 500 stretching cycles and 1000 compression cycles), and efficient warmth retention properties (thermal conductivity of 23.92 mW m-1 K-1). Furthermore, the introduction of a flame retardant enables the NAMS to possess remarkable flame resistance, with a limiting oxygen index of 28.7%. The development of NAMS offers a promising avenue for future advancements in ultralight, flame-retardant, and high-efficiency warmth retention materials.