Association of health insurance coverage disruptions and breast and colorectal cancer screening.

BACKGROUND: Health insurance coverage is critical for ensuring access to recommended health care in the United States. This study investigated the associations of health insurance coverage disruptions, also known as coverage churn, and receipt of breast and colorectal cancer screening. METHODS: Adults who were age-eligible and younger than 65 years (range, 50-64 years) for breast (n = 17,128 women) and colorectal (n = 32,562 individuals) cancer screening were identified from 5 years of the National Health Interview Survey. Adults were categorized into five groups based on insurance type at survey (private, public, none) and prior coverage disruptions within the past year. Screening outcomes included: (1) ever-screened, (2) past-year screening, and (3) guideline-concordant screening. Separate multivariate logistic regression models were used to evaluate the associations between insurance coverage disruptions and cancer screening. RESULTS: Among adults who had coverage at the time of the survey, 3.1% with private insurance and 6.5% with public insurance reported prior coverage disruptions. Individuals without health insurance coverage had the lowest level of screening. Among individuals who had private coverage, prior disruptions were associated with lower guideline-concordant screening in adjusted analyses (breast cancer screening: adjusted prevalence ratio [aPR], 0.82; 95% confidence interval [CI], 0.75-0.89; colorectal cancer screening: aPR, 0.78; 95% CI, 0.72-0.86); among those who had public coverage, prior disruptions were also associated with lower guideline-concordant breast cancer screening (aPR, 0.73; 95% CI, 0.60-0.89) and colorectal cancer screening (aPR, 0.84; 95% CI, 0.72-0.99). CONCLUSIONS: Health insurance coverage disruptions were associated with lower past-year and guideline-concordant breast and colorectal cancer screening. The current findings underscore the importance of stable health insurance coverage to improve cancer screening and early detection when treatment is most effective.

Optimal testing time for cerebral heterotopia formation in the rat comparative thyroid assay, a downstream indicator for perinatal thyroid hormone insufficiency.

In a past study, we proposed a modified Comparative Thyroid Assay (CTA) with additional examinations of brain thyroid hormone (TH) concentrations and brain histopathology but with smaller group sizes. The results showed that the modified CTA in Sprague Dawley rats detected 10 ppm 6-propylthiouracil (6-PTU)-induced significant suppressions of serum/brain TH concentrations in offspring. To confirm the reliability of qualitative brain histopathology and identify the optimal testing time for heterotopia (a cluster of ectopic neurons) in the modified CTA, brain histopathology together with serum/brain TH concentrations were assessed in GD20 fetuses and PND2, 4, 21, and 28 pups using a similar study protocol but with a smaller number of animals (N=3-6/group/time). Significant hypothyroidism was observed and brain histopathology revealed cerebral heterotopia formation in PND21 and PND28 pups, with likely precursor findings in PND2 and PND4 pups but not in GD20 fetuses. This study confirmed that the optimal testing time for cerebral heterotopia in rat CTA was PND21 and thereafter. These findings suggest that cerebral heterotopia assessment at appropriate times may be a useful alternative to the original CTA design.

Shared Experiences of Nurse Anesthesiology Faculty During the COVID-19 Pandemic.

The COVID-19 pandemic impacted all aspects of healthcare, including the education of certified registered nurse anesthesiologists. While the literature contains reports of the impact of COVID-19 on physician anesthesiologist faculty, there was no research identified describing the impact on nurse anesthesiologist faculty. The purpose of this study was therefore to describe and explore the impact of the COVID-19 pandemic on nurse anesthesiology faculty. This qualitative ethnographic study used small focus groups and semistructured and probing questions to examine the phenomenon of interest. Through thematic analysis of the narrative, five overarching themes were identified: 1) ability to adapt to adversity, 2) disruption leads to change, 3) perceived positive outcomes, 4) previously untapped resources, and 5) curricular innovation and integrity.

Investigating Longitudinal Trajectories of COVID-19 Disruption: Methodological Challenges and Recommendations.

Relatively few studies have longitudinally investigated how COVID-19 has disrupted the lives and health of youth beyond the first year of the pandemic. This may be because longitudinal researchers face complex challenges in figuring out how to code time, account for changes in COVID-19 spread, and model longitudinal COVID-19-related trajectories across environmental contexts. This manuscript considers each of these three methodological issues by modeling trajectories of COVID-19 disruption in 1080 youth from 12 cultural groups in nine nations between March 2020-July 2022 using multilevel modeling. Our findings suggest that for studies that attempt to examine cross-cultural longitudinal trajectories during COVID-19, starting such trajectories on March 11, 2020, measuring disruption along 6-month time intervals, capturing COVID-19 spread using death rates and the COVID-19 Health and Containment Index scores, and using modeling methods that combine etic and emic approaches are each especially useful. In offering these suggestions, we hope to start methodological dialogues among longitudinal researchers that ultimately result in the proliferation of research on the longitudinal impacts of COVID-19 that the world so badly needs.

The devastating dance between opioid and housing crises: Evidence from OxyContin reformulation.

Housing instability and drug misuse are two of the United States' most pressing challenges, each bearing profound health and societal consequences. A crucial yet largely underexplored question is the extent to which the opioid crisis has intensified housing instability. Our study ventures into this relatively uncharted nexus, investigating how the OxyContin reformulation, a pivotal moment in the U.S. opioid epidemic, impacted eviction rates. Employing a dose-response Difference-in-Differences model and analyzing eviction data from 2004 to 2016, we demonstrate that the OxyContin reformulation precipitated a significant increase in evictions, especially in areas with weak eviction protections or limited access to psychiatric treatment resources. Channel analyses reveal increased marijuana initiation and heightened mental and physical health issues following the reformulation. Moreover, the OxyContin reformulation leads to greater reliance on the Supplemental Nutrition Assistance Program, signaling an escalated financial strain on governmental resources. Finally, we find evidence of increased marital disruption post-reformulation. Our findings underscore the urgent need for collaborative efforts between public health and housing authorities to address both the opioid and housing crises.

Association Between Blood-Brain Barrier Disruption and Stroke-Associated Pneumonia in Acute Ischemic Stroke Patients After Endovascular Therapy: A Retrospective Cohort Study.

Background: Stroke, particularly due to large vessel occlusion (LVO), is a major cause of mortality and disability globally. Endovascular therapy (ET) significantly improves outcomes for acute ischemic stroke (AIS) patients, but complications such as stroke-associated pneumonia (SAP) increase mortality and healthcare costs. This study investigates the association between blood-brain barrier (BBB) disruption and the increased risk of SAP and explores the relationship between BBB disruption and medium-term functional outcomes. Methods: The retrospective cohort study was performed on AIS patients enrolled between January 2019 to February 2023 who underwent ET. Patients were divided into two groups: BBB disruption and without BBB disruption. Multiple logistic regression model was conducted to measure the association between BBB disruption and SAP. Mediation analysis was used to estimate the potential mediation effects on the associations of BBB disruption with SAP. A restricted cubic spline (RCS) regression model was used to further outline the connection between the highest CT value of hyperattenuated lesions areas and the risk of SAP. Results: The study included 254 patients who underwent endovascular therapy, with 155 patients in the BBB disruption group (exposure) and 99 patients in the without BBB disruption group (control). Multiple logistic regression analysis revealed a significantly increased risk of SAP in patients with BBB disruption (OR = 2.337, 95% CI: 1.118-4.990, p = 0.025). Furthermore, mediation analysis suggested that this association may be partly due to malignant cerebral oedema and haemorrhagic transformation. The study found an inverse L-shaped dose-response relationship between the maximum CT values of BBB disruption areas and the incidence of SAP. SAP partially mediated the association between BBB disruption and 3-month poor functional outcome. Conclusion: BBB disruption are a potential risk factor for SAP. BBB disruption may affect short- and medium-term prognosis of patients after ET in part through SAP.

A Dual Action Platinum(IV) Complex with Self-assembly Property Inhibits Prostate Cancer through Mitochondrial Stress Pathway.

Platinum(IV) prodrugs are highly promising anticancer agents because they can selectively target tumors and minimize the adverse effects associated with their PtII congeners. In this study, we synthesized dual action PtIV complexes by linking oxoplatin with lithocholic acid. The synthesized compounds, designated as PL-I, PL-II, and PL-III, can spontaneously self-assemble in water, resulting in the formation of spherical shape nanoparticles. Among the developed complexes, PL-III appeared to be the most potent compound against all the tested cancer cell lines, with 10 fold higher cytotoxicity compared to cisplatin in PC3 cells. The complex arrests the cell cycle in the S and G2 phases and induces DNA damage. Additional mechanistic investigations demonstrate that PL-III predominantly localizes within the mitochondria and cytoplasm. Consequently, PL-III disrupts mitochondrial membrane potential, increases ROS production, and perturbs mitochondrial bioenergetics in PC3 cells. The complex induces apoptosis through the mitochondrial pathway by upregulating pro-apoptotic protein expression and downregulating anti-apoptotic protein expression from the BCl-2 protein family. These results demonstrate that higher cellular uptake and reduction of PL-III by biological reductants in PC3 cells resulted in a synergistic effect of lithocholic acid and cisplatin, which can be easily observed due to its unique cytotoxic mechanism. This further underscores the significance of dual-action PtIV complexes in enhancing the efficacy of cancer therapy.

Profiling the endocrine disrupting properties of triazines, triazoles and short-chain PFAS.

Persistent, mobile and toxic (PMT) compounds released to the environment are likely to pollute drinking water sources due to their slow environmental degradation (persistency) and high water solubility (mobility). The aim of the present study was to create in vitro hazard profiles for sixteen triazoles, nine triazines and eleven PFAS based on their agonistic and antagonistic effects in estrogen receptor (ER), androgen receptor (AR) and thyroid hormone receptor (TR) reporter gene assays, their ability to bind human transthyretin (TTR), and their effects on steroidogenesis. The triazole fungicides tetraconazole, bitertanol, fenbuconazole, tebuconazole, cyproconazole, difenoconazole, propiconazole, paclobutrazol and triadimenol had agonistic or antagonistic effects on the ER and AR. Difenoconazole, propiconazole and triadimenol were also found to be TR antagonists. The triazine herbicide ametryn was an ER, AR and TR antagonist. The same nine triazole fungicides and the triazines atrazine, deethyl-atrazine and ametryn affected the secretion of steroid hormones. Furthermore, PFAS compounds PFBS, PFHxS, PFHxA, PFOS, PFOA and GenX and the triazoles bitertanol, difenoconazole and 4-methyl benzotriazole were found to displace T4 from TTR. These results are in line with earlier in vitro and in vivo studies on the endocrine disrupting properties of triazines, triazoles and PFAS. The present study demonstrates that this battery of in vitro bioassays can be used to profile compounds from different classes based on their endocrine disrupting properties as a first step to prioritize them for further research, emission reduction, environmental remediation and regulatory purposes.

Dose and timing effects of caffeine on subsequent sleep: A randomised clinical crossover trial.

STUDY OBJECTIVES: To investigate the effect of a typical dose of caffeine and a high dose of caffeine consumed in the morning, afternoon, and evening on subsequent sleep. METHODS: Using a placebo-controlled, double-blind, randomised crossover design, 23 males (25.3±5.0 years) with a moderate habitual caffeine intake (<300mg∙day-1) completed seven conditions: placebo, and 100 and 400mg of caffeine consumed 12, eight, and four hours prior to bedtime, with a 48-hour washout. In-home partial polysomnography and sleep diaries were used to assess sleep. Linear mixed models estimated the effect of each condition. RESULTS: No significant effect on objective or subjective sleep occurred with the 100mg dose of caffeine compared to the placebo (p>0.05) but significant effects occurred with the 400mg dose (p<0.05). Significant delays in sleep initiation and alterations to sleep architecture were observed when 400mg was consumed within 12 hours of bedtime (p<0.05), and significantly greater sleep fragmentation occurred when 400mg was consumed within eight hours of bedtime (p<0.05). Additionally, perceived sleep quality was significantly reduced when 400mg was consumed four hours prior to bedtime (-34.02%, p=.006) but not at eight or 12 hours. CONCLUSIONS: A 100mg dose of caffeine can be consumed up to four hours prior to bedtime, but 400mg may negatively impact sleep when consumed as one dose within 12 hours of bedtime, with the adverse influence on sleep increasing the closer consumption occurs to bedtime. The discrepancy between objective and subjective sleep quality suggests individuals may have difficulty accurately perceiving the influence of caffeine on sleep quality.

New antibiofilm strategies for the management of nontuberculous mycobacteria diseases.

INTRODUCTION: Nontuberculous mycobacteria (NTM) represent a group of microorganisms comprising more than 190 species. NTM infections have increased recently, and their treatment is a major challenge because to their resistance to conventional treatments. This review focuses on innovative strategies aimed at eradicating NTM biofilms, a critical factor in their resistance. Important areas addressed include biofilm formation mechanisms, current therapeutic challenges, and novel treatment approaches. The main objective is to compile and analyze information on these emerging strategies, identifying pivotal research directions and recent advancements. AREAS COVERED: A review of the scientific literature was conducted to identify emerging novel therapies for the treatment of NTM infections and to explore potential synergies with existing treatments. EXPERT OPINION: Experts highlights a limited understanding of optimal treatment regimens, often supported by insufficient scientific evidence. Current therapies are typically prolonged, involve multiple antibiotics with adverse effects, and frequently do not achieve patient cure. Certain species are even considered virtually impossible to eradicate. A thorough understanding of these new approaches is imperative for improving patients outcomes. This review provides a robust foundation for developing of more effective antibacterial strategies, which are essential because of the increasing incidence of NTM infections and the limitations of existing therapies.

Sociodemographic and dietary predictors of maternal and placental mycoestrogen concentrations in a US pregnancy cohort.

BACKGROUND: Zearalenone (ZEN) is a mycotoxin contaminating grains and processed foods. ZEN alters nuclear estrogen receptor α/ß signaling earning its designation as a mycoestrogen. Experimental evidence demonstrates that mycoestrogen exposure during pregnancy is associated with altered maternal sex steroid hormones, changes in placental size, and decreases in fetal weight and length. While mycoestrogens have been detected in human biospecimens worldwide, exposure assessment of ZEN in US populations, particularly during pregnancy, is lacking. OBJECTIVE: To characterize urinary and placental concentrations of ZEN and its metabolites in healthy US pregnant people and examine demographic, perinatal, and dietary predictors of exposure. METHODS: Urine samples were collected in each trimester from pregnant participants in the UPSIDE study and placenta samples were collected at delivery (Rochester, NY, n = 317). We used high performance liquid chromatography and high-resolution tandem mass spectrometry to measure total urinary (ng/ml) and placental mycoestrogens (ng/g). Using linear regression and linear mixed effect models, we examined associations between mycoestrogen concentrations and demographic, perinatal, and dietary factors (Healthy Eating Index [HEI], ultra-processed food [UPF] consumption). RESULTS: Mycoestrogens were detected in 97% of urines (median 0.323 ng/ml) and 84% of placentas (median 0.012 ng/g). Stability of urinary mycoestrogens across pregnancy was low (ICC: 0.16-0.22) and did not correlate with placental levels. In adjusted models, parity (multiparous) and pre-pregnancy BMI (higher) predicted higher urinary concentrations. Birth season (fall) corresponded with higher placental mycoestrogens. Dietary analyses indicated that higher HEI (healthier diets) predicted lower exposure (e.g., Σmycoestrogens %∆ -2.03; 95%CI -3.23, -0.81) and higher percent calories from UPF predicted higher exposure (e.g., Σmycoestrogens %∆ 1.26; 95%CI 0.29, 2.24). IMPACT: The mycotoxin, zearalenone (ZEN), has been linked to adverse health and reproductive impacts in animal models and livestock. Despite evidence of widespread human exposure, relatively little is known about predictors of exposure. In a pregnant population, we observed that maternal ZEN concentrations varied by maternal pre-pregnancy BMI and parity. Consumption of ultra-processed foods, added sugars, and refined grains were linked to higher ZEN concentrations while healthier diets were associated with lower levels. Our research suggests disparities in exposure that are likely due to diet. Further research is needed to understand the impacts of ZEN on maternal and offspring health.

Occupational Participation Among Older Adults During the COVID-19 Pandemic.

Background. The COVID-19 pandemic led to abrupt occupational disruption for all people. However, some populations, like older adults, were disproportionately impacted particularly in the earlier waves. Purpose. The purpose of this study was to explore and understand how the occupational participation of community-dwelling older adults was experienced during the COVID-19 pandemic, using the Canadian Model of Occupational Participation (CanMOP) to contextualize findings. Method. Sixty-seven older adults participated in semi-structured interviews from September 2020 to May 2021, 37 of which also participated in a follow-up interview one-year later. Findings. Using reflexive thematic analysis, four themes were generated: (1) experiences of loss are complex and layered for older adults, (2) technology as a medium for occupational participation, (3) risk perception influences return to occupation, and (4) age-related challenges for older adults resuming volunteer work. Conclusion. Increasing frequency and severity of influenza pandemics and other disasters are a global concern, and OTs can use their skillsets to foster participation and expand occupational possibilities for older adults. The CanMOP was a helpful tool to understand the nuances underlying the participation of older adults in this context.

The Role of Human Adiponectin Receptor 1 in 2-Ethylhexyl Diphenyl Phosphate Induced Lipid Metabolic Disruption.

Epidemiological evidence links exposure to 2-ethylhexyl diphenyl phosphate (EHDPP) with lipid metabolic disruption, typically attributed to nuclear receptors, while the role of membrane receptors remains underexplored. This study explored the role of adiponectin receptor 1 (AdipoR1) in EHDPP-induced lipid metabolic disturbances. We examined EHDPP's binding affinity and transcriptional impact on AdipoR1. AdipoR1 knockdown (AdipoR1kd) human liver cells and coculture experiments with AdipoR1 activator (AdipoRon) were used to investigate the effect and the mechanism. EHDPP disrupted triglyceride and phospholipid synthesis and altered corresponding gene expression, mirroring effects in AdipoR1kd cells but diminishing in EHDPP-treated AdipoR1kd cells. RNA sequencing revealed that EHDPP primarily disrupted oxidative phosphorylation and insulin signaling dependent on AdipoR1. Mechanistically, EHDPP interacted with AdipoR1 and reduced AdipoR1 protein levels at 10-7 mol/L or higher, weakening the activation of the calmodulin dependent protein kinase ß (CaMKKß)/AMPK/acetyl CoA carboxylase pathway. Furthermore, EHDPP pretreatment blocked the increase in Ca2+ flux and the corresponding kinase CaMKKß, as well as liver kinase B1 (LKB1) activation induced by AdipoRon, which is necessary for AMPK activation. Collectively, these findings demonstrate that EHDPP-induced lipid imbalance is partially dependent on AdipoR1, expanding the understanding of environmental metabolic disruptors beyond nuclear receptors.

Sensing Sociality: Disruptions of Social Life When Living With Chemosensory Dysfunctions After COVID-19.

Taste and smell are of direct importance in most social interactions. Radical disruptions in these senses can, therefore, substantially disrupt sociality. This paper focuses on the experiences of a particular type of disruption: persistent chemosensory dysfunctions after COVID-19. We conducted semi-structured interviews with 30 patients undergoing treatment for chemosensory dysfunctions and analyzed the ways in which their experiences have influenced social relations and activities, particularly regarding food and eating. The findings reveal that these dysfunctions have made the participants markedly aware that food and eating are pivotal to full participation in social life. As is smell, both surrounding smells and the perception of one's own smell, with dysfunctions leading to several social consequences. Such problems are handled through both avoidance behavior and adaptations. While adaptations facilitate interactions, they come at the cost of feeling a burden to others or not fully appreciating an event (e.g., a shared meal). Social support is of great importance, ranging from minor practical assistance, such as a friend checking if the milk is sour, to the profound emotional relief felt from empathic treatment and recognition that the problems are real. Here, healthcare professionals can play a vital role, even in the (perceived) absence of clinical effectiveness of the treatment. The experiences expressed are partially in line with other manifestations of Long COVID and with chemosensory dysfunctions due to other illnesses, but only partially, since this is a patient group with needs and experiences that are unique, in that sociality is so strongly affected solely by disruptions in sensory abilities.

Oleanolic acid derivatives against drug-resistant bacteria and fungi by multi-targets to avoid drug resistance.

Mixed infections caused by drug-resistant bacteria and fungi pose a severe threat to human health, and multi-target drugs may provide an effective approach to combat drug-resistant pathogens. Therefore, this study aimed to investigate the efficacies of some oleanolic acid (OA) derivatives against multidrug-resistant (MDR) bacteria and fungi using in vitro and in vivo experiments. Novel amphiphilic OA derivatives were designed and optimised, in which compounds G1 and J1 exhibited effective antimicrobial activity (MICs = 1-2 µg/mL), high selectivity against MDR strains, rapid bactericidal activity, and good predictive pharmacokinetics. Mechanistically, both compounds prevented drug resistance by disrupting the bacterial cell membrane, inserting into the DNA, and binding to DNA gyrase. Additionally, J1 reduced microbial count in a mouse MRSA skin infection model and accelerated wound healing much better than vancomycin. Conclusively, this study presents a new class of potential drugs for resistant bacteria and fungi.

Antibacterial Activity of Recombinant Liver-Expressed Antimicrobial Peptide-2 Derived from Olive Flounder, Paralichthys olivaceus.

Liver-expressed antimicrobial peptide-2 (LEAP-2) is a cysteine-rich peptide that plays a crucial role in the innate immune system of fish. To investigate the molecular function of LEAP-2 from olive flounder, Paralichthys olivaceus, we cloned the gene encoding LEAP-2 using PCR and expressed it in Escherichia coli. Analysis of LEAP-2 expression revealed predominant transcripts in the liver and lower levels in the intestine of olive flounder, whereas their expression levels in the liver and head kidney increased, during the initial stage of infection with the aquapathogenic bacterium Edwadrsiella piscicida. Recombinant LEAP-2 (rOfLEAP-2) purified from E. coli exhibited antimicrobial activity, as demonstrated by the ultrasensitive radial diffusion assay, against both Gram-positive (Bacillus subtilis, Streptococcus parauberis, and Lactococcus garvieae) and Gram-negative (Vibrio harveyi and E. coli) bacteria, with minimum inhibitory concentrations ranging from 25 to 100 µg/mL depending on the species tested. The antibacterial activity of rOfLEAP-2 was attributed to its ability to disrupt bacterial membranes, validated by the N-phenylnaphthalen-1-amine uptake assays and scanning electron microscope analysis against E. coli, V. harveyi, B. subtilis, and L. garvieae treated with rOfLEAP-2. Furthermore, a synergistic enhancement of antibacterial activity was observed when rOfLEAP-2 was combined with ampicillin or synthetic LEAP-1 peptide, suggesting a distinct mechanism of action from those of other antimicrobial agents. These findings provide evidence for the antibacterial efficacy of LEAP-2 from olive flounder, highlighting its potential therapeutic application against pathogenic bacteria.

Associations between Variability in Between- and Within-day Dietary Intake with Adiposity and Glucose Homeostasis in Adults: A Systematic Review.

This systematic review aims to comprehensively evaluate the literature regarding the impact of variations in dietary intake, both between- and within-days, on adiposity and glucose metabolism. We included observational and experimental articles obtained from PubMed, Scopus, Cochrane Library, and gray literature until October 9, 2023, evaluating the impact of between- or within-day variations in meal, energy, or macronutrient intake on these outcomes. Our focus was on adults aged ≥18y, spanning both healthy individuals and those with type 2 diabetes mellitus (T2DM). Given the diverse range of exposures, treatments, and outcomes among the selected articles, we chose a qualitative synthesis approach to effectively analyze the data. Eighty articles from 43 observational and 37 experimental studies were included, involving 89,178 participants. Patterns of dietary intake variation were identified and systematically organized into distinct categories based on similarities. Between-day variations in dietary intake consisted of between-day variations in both the quantity consumed and meal timing. Meanwhile, within-day variations encompassed factors such as eating window, meal omission, within-day meal timing, within-day variation in dietary intake quantity, and temporal distribution. Despite mixed results, time-restricted eating was generally associated with lower adiposity. However, limited control for total daily energy intake (TDEI) suggests that the contribution of lower energy intake cannot be conclusively excluded. Conversely, the adverse effect of meal omission on glucose parameters was consistently supported by randomized trials. Interestingly, the results showed that consuming a substantial portion of TDEI in the morning may increase the likelihood of observing improvements in adiposity. Furthermore, inconsistencies in outcomes across articles examining the effects in healthy versus T2DM populations, or in energy-sufficient vs deficient individuals, indicate potential condition-specific effects. These findings support the need for further investigation into the effects of between- and within-day variations in dietary intake to better understand their impact on adiposity and glucose homeostasis.

Impact of polyethylene microplastics exposure on kallikrein-3 levels, steroidal-thyroidal hormones, and antioxidant status in murine model: protective potentials of naringin.

The widespread presence of microplastics in the environment has raised significant concerns regarding their potential impact on human and animal health. Among various microplastic types, polyethylene microplastics (PE-MPs) are particularly prevalent due to the extensive use in packaging and consumer products. Exploring the uncharted therapeutic potentials of naringin, this study delves into its mitigating effects on disruptions in kallikrein-3 levels, steroidal-thyroidal hormone balance, and antioxidant defense triggered by PE-MPs exposure, paving the way for novel interventions in environmental toxin-induced endocrine and oxidative stress disorders. Male Wistar rats (n = 24) were randomly grouped into four: Control, PE-MPs (1.5 mg/kg), PE-MPs + NAR (1.5 mg/kg PE-MPs + 100 mg/kg NAR), and NAR (100 mg/kg). Hormonal and antioxidant parameters were assessed after 28 days of exposure. PE-MPs exposure caused a significant increase(p < 0.005) in the level of kallikrein-3 (KLK-3) while it significantly reduces the levels of testosterone (TST), luteinizing hormone, thyroid stimulating hormone (TSH) and Free-triiodothyronine (fT3) and Total cholesterol (TChol) concentration. PE-MPs exposure also disrupted significantly (p < 0.005) antioxidant profile by down-regulating the activities of glutathione-S-transferase, catalase (CAT), superoxide dismutase (SOD) and reducing levels of glutathione (GSH) and ascorbic acid (AA) while concentration of malondialdehyde (MDA) levels were increased relative to control. However, the mitigating potentials of naringin on disruptions in hormonal and antioxidant profiles caused by PE-MPs exposure were demonstrated, as NAR normalized KLK-3, steroid, and thyroid hormone levels, cholesterol concentration, and enhanced antioxidant defense. This suggests that NAR is a promising protective agent against endocrine and oxidative damage induced by environmental contaminants such as microplastics.

Biodistribution of synthesized polyethylene terephthalate fibers in adult zebrafish, their sex hormone disruption effect, and mitigation using natural organic matter.

Although polyethylene terephthalate (PET) fibers are a representative form of plastic pollutants, studies on their toxicity are currently limited compared to other plastic types. Moreover, the effect of natural organic matter (NOM) on their toxicity has not been investigated. In this study, female and male adult zebrafish were exposed to synthesized PET fibers at concentrations of 0.1, 1, 10, and 100 mg/L in the presence and absence of 10 mg/L of NOM for 10 d. Bioaccumulation of PET fibers in zebrafish intestine, liver, and gills was identified and expression levels of reactive oxygen species (ROS) generation, sex hormones, and oxidative stress and sex hormone-related genes were measured. In addition, the developmental stages of gonadal cells were examined through histological analysis. We found that PET fibers bioaccumulated in the intestine and liver of zebrafish. ROS generation significantly increased at 100 mg/L of PET fibers, the expression of oxidative stress-related genes decreased in female and increased in male zebrafish. Exposure to 100 mg/L of PET fibers did not affect 17-beta estradiol, but significantly decreased the testosterone levels in male zebrafish. Sex hormone-related genes significantly decreased in both female and male zebrafish, except for androgen receptor in female zebrafish. However, these changes were exacerbated by the removal of NOM, suggesting a protective effect of NOM against PET fibers toxicity. We demonstrated that the accumulated PET fibers may lead to oxidative stress and sex hormone alteration, and disrupt the development of gonadal cells. Additionally, the NOM coating did not alter bioaccumulation considerably, but mitigated the adverse effects at the hormone level in PET fiber-exposed zebrafish. Thus, this study provides a basis for further research on the toxicity assessment of PET fibers and interactions between NOM and PET fiber-related toxicity.

Thyroid Endocrine Disruption and Mechanism of the Marine Antifouling Pollutant 4,5-Dichloro-2-n-octyl-4-isothiazolin-3-one.

The antifoulant 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) is an emerging pollutant in the marine environment, which may disrupt the thyroid endocrine system. However, DCOIT toxicity in relation to thyroid endocrine disruption and the underlying mechanisms remains largely unclear. In this study, in vivo, in silico, in vitro, and ex vivo assays were performed to clarify DCOIT's thyroid toxicity. First, marine medaka (Oryzias melastigma) were exposed to environmentally realistic concentrations of DCOIT for an entire life cycle. The results demonstrated that DCOIT exposure potently stimulated the hypothalamic-pituitary-thyroid axis, characterized by hyperthyroidism symptom induction and prevalent key gene and protein upregulation in the brain. Moreover, the in silico and in vitro results evidenced that DCOIT could bind to thyroid hormone receptor ß (TRß) and interact synergistically with triiodothyronine, thus promoting GH3 cell proliferation. The CUT&Tag experiment found that DCOIT interfered with the affinity fingerprint of TRß to target genes implicated in thyroid hormone signaling cascade regulation. Furthermore, ex vivo, Chem-seq revealed that DCOIT directly bound to the genomic sequences of thyrotropin-releasing hormone receptor b and thyroid-stimulating hormone receptor in marine medaka brain tissues. In conclusion, the current multifaceted evidence confirmed that DCOIT has a strong potency for thyroid endocrine system disruption and provided comprehensive insights into its toxicity mechanisms.