Biology and Life Sciences

Abstract: The microbiota-gut-brain axis (MGBA) represents a bidirectional neuroendocrine system essential for maintaining metabolic and neurological homeostasis. While dietary macronutrients are known modulators of this axis, the cumulative impact of modern industrial xenobiotics remains insufficiently characterized. This review synthesizes contemporary, multidisciplinary evidence to elucidate how four ubiquitous environmental stressors Particulate Matter (PM2.5), Microplastics (MPs), Inorganic Nanoparticles (NPs), and Non-Nutritive Sweeteners (NNS) synergistically perturb this delicate enteric ecosystem. We integrate independent lines of research to propose a unifying pathological framework: these agents induce profound dysbiosis, significantly depleting beneficial, short chain fatty acid (SCFA) producing taxa (e.g., Lachnospiraceae, Faecalibacterium) and sharply diminishing the bioavailability of critical neuroactive mediators, including butyrate, GABA, serotonin, and indole derivatives. Concurrently, NNS-driven bacteriostatic shifts, the MP “plastisphere” phenomenon, and NP-induced oxidative mucosal abrasion critically compromise the intestinal barrier. This “leaky gut” facilitates the unrestricted systemic translocation of lipopolysaccharides (LPS) and trimethylamine-N-oxide (TMAO), driving a peripheral Treg/Th17 immune imbalance that propagates via the gut-liver and gut-heart axes directly to the central nervous system (CNS). Crucially, the synthesis of this data points toward a potential “Dual-Hit” mechanism, suggesting that these xenobiotics aggravate neurological pathology through simultaneous mechanisms: acting as direct neurotoxicants via CNS translocation (e.g., NPs crossing the blood-brain barrier to trigger epigenetic reprogramming and amyloid aggregation) while concurrently driving “bottom-up” systemic neuroinflammation. By linking these disruptions to classic neurodegeneration (Alzheimer’s, Parkinson’s) as well as underexplored pathologies (migraine, epilepsy, restless leg syndrome, and substance use disorders), this review underscores the urgent need for a paradigm shift in environmental neurotoxicology and the development of targeted microbiome-based interventions.

Abstract: Lipid nanoparticles (LNPs) are central to modern mRNA therapeutics, including COVID‑19 vaccines. Far from passive carriers, their ionizable lipids actively interact with cellular membranes. Evidence from cellular, transcriptomic, and proteomic studies indicates that LNPs, with or without nucleic acid, alter gene and protein expression, thereby initiating inflammatory, detoxification, and stress responses at the membrane. Key pathways affected include lipid metabolism and detoxification, with roles for Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) and cytochrome P450 enzymes. We hypothesize that the phosphatidylinositol (PI) cycle is the primary site of LNP-induced perturbations, regulating membrane restructuring and organelle trafficking during endocytosis. Disruption of this cycle triggers downstream signaling cascades, including Nuclear Factor kappa B (NF-κB), Mitogen-Activated Protein Kinases (MAPKs), Janus kinase/signal transducers and activators of transcription (JAK/STAT), and Mechanistic Target of Rapamycin (mTOR). We term this systemic effect lipid-nanoparticle-driven membrane dysfunction (L‑DMD), characterized by dysregulated cellular communication, stress responses, and energy balance. This review provides a mechanistic framework for understanding the persistent biological effects of modified modRNA-LNP exposure and emphasizes a systems-level intracellular perspective.

Abstract: The recreational use of fentanyl (FT) combined with xylazine (XZ), known as “tranq-dope,” poses a growing public health threat due to its high toxicity and mortality. This study evaluated the effectiveness of naloxone (NX), its lipophilic prodrug NX90, and their combinations with the κ-agonist/µ-antagonist nalbuphine (NB) in reversing overdose and restoring respiratory function in a rat model. At the low FT dose (0.052 mg/kg), adding XZ (1 mg/kg) shortened time to overdose by ~2,600 seconds compared with FT alone, whereas onset times were similar at medium and high FT doses. Respiratory rate at overdose was also higher with XZ, showing a 2.2-fold increase at high FT doses. Most interventions did not significantly shorten time to reversal. Only NX+NB in females and NX90+NB in both sexes reduced reversal time compared with NX alone. However, respiratory rate at reversal was significantly improved with NX+NB, ½NX90+NB, and NX90+NB (90–92 breaths/min) compared with naloxone alone (80 ± 6 breaths/min). Interventions containing nalbuphine (κagonist/µantagonist) yielded higher RR and HR at reversal than NX alone, suggesting a contribution of κagonism to physiological recovery. In this FT+XZ dose range, coadministration of xylazine (1 mg/kg) was associated with higher respiratory rates at the time of overdose onset across ascending fentanyl doses, blunting the dosedependent RR decline observed with fentanyl alone at that specific endpoint. Comparable or improved reversal outcomes could be achieved using half-doses of NX or NX90 with NB—potentially reducing total dose of naloxone and mitigating the risk of precipitated withdrawal in individuals with opioid use disorder.

Abstract: Background/Objectives: Excessive dietary inorganic phosphate (Pi) as a food additive poses potential health risks. Methods: This study investigates its impact on intestinal and immune homeostasis in mice using gradient Pi exposure combined with an inflammatory model. Results: Pi overload induced atrophy in the thymus, spleen, and kidney, damaged the intestinal barrier, reduced villus height‑to‑crypt depth ratio, and decreased goblet cell numbers. Altered levels of serum sIgA and IgE, as well as intestinal IgA, IgG, IgE, and IgM, together with decreased IFNα, indicated disrupted immune balance caused by Pi treatment. Proteomic analysis revealed differential expression of key proteins, including CNTFR and Bcl2l1 in the JAK‑STAT pathway, and metabolic regulators CPT1α and IDH1, compared Pi treated mice with the control group. Conclusions: These findings suggest Pi may affect immune and neuronal functions through tumor‑related signaling and mitochondrial pathways, providing insight into the health implications of Pi overconsumption.

Abstract:

Benthic foraminifera, worldwide single-cell marine organisms, represent an important component of seabed ecosystems. Due to their sensitivity to environmental changes, they are often used as bioindicators, providing an efficient tool in toxicity studies. Among the pollutants affecting marine coastal and estuarine environments, persistent flame retardants such as polybrominated diphenyl ethers (PBDEs) are frequently found. Low-level exposure to BDE-47, a PBDE congener, is known to affect organisms development. In this framework, this study aims to assess the effects of BDE-47 exposure on benthic foraminifera from coastal marine environments. Foraminifera specimens belonging to the symbiont-bearing Peneroplidae family were sampled and exposed to two different BDE-47 concentrations from T0 up to 48 h (T48). Vitality indicators such as changes in pseudopodial activity, movement, reproduction, loss of symbiont algae, and eventual death were monitored during the experiment. Exposure to BDE-47 induced alterations in pseudopodial activity, movement, reproduction, and symbiont retention, with progressive loss of vitality and eventual mortality at increasing exposure levels, highlighting the sensitivity of this species to BDE-47 exposure. These findings suggest the harmful repercussions of PBDE pollution on marine coastal ecosystems, affecting benthic organisms and potentially contributing to biomagnification processes within the food web, with possible implications for human health.

Abstract: Parkinson’s disease (PD) is a neurodegenerative disorder with limited disease-modifying therapies. Computational models can provide predictive insights into drug properties, although critically limited datasets pose challenges. Fifteen FDA-approved Parkinson’s disease drugs were represented as hydrogen-suppressed molecular graphs. Twelve degree-based topological indices were computed and used as descriptors for predicting seven physicochemical properties (MR, P, MV, MW, nHA, nRotB, Complexity). Multi-layer perceptron artificial neural network (ANN) and Random Forest (RF) models were trained. Model performance was evaluated using Leave-One-Out Cross-Validation (LOOCV). The statistical robustness of the models was verified using a Y-randomization test. Shapley Additive Explanations (SHAP) were applied for interpretability. The ANN demonstrated high predictive correlation on the small dataset for MR (R² = 0.876), P (R² = 0.875), MW (R² = 0.837), and nHA (R² = 0.901). Lower predictive performance was observed for MV (R² = 0.729), molecular Complexity (R² = 0.706), and nRotB (R² = 0.308). RF provided comparable results but was generally outperformed by ANN. The Y-randomization test yielded consistently negative average R²rand values (lowest R²rand = -1.708), confirming the absence of chance correlation. SHAP analysis identified the most influential topological indices for each property in ANN. ANN-based QSPR modeling with degree-based descriptors can accurately predict physicochemical properties of PD drugs for certain endpoints. These models were proven statistically robust through Y-randomization validation. Limitations include the small dataset size and high-dimensional descriptor space, highlighting the need for external validation, larger datasets, and inclusion of additional 3D/quantum descriptors for more complex pharmacokinetic endpoints.

Abstract: Biochar, a carbon-rich material traditionally used to improve soil health and as a feed additive, has recently attracted attention for its potential biological activity. This study investigated the effects of an aqueous biochar extract (BC-AE) on human intestinal epithelial cells (Caco-2), specifically examining its impact on cell viability and apoptosis. The metabolic activity of Caco-2 cells exposed to BC-AE was first evaluated using an MTS assay. A concentration of 3 mg/mL, which promoted Caco-2 metabolic activity, was selected for further testing at 24 and 72 hours. The effect of BC-AE on cell viability was assessed by epifluorescence microscopy (morphology) and flow cytometry (apoptosis profiling). The transcriptional response of cell viability-related genes (BAX, BAD, BCL-2, BCL-xL, MCL-1, P21, and P53) and microRNAs (miR-15b, miR-19, miR-21, miR-33a, miR-155, and miR-486) was analyzed by RT-qPCR. In parallel, selected proteins (BAD, BAX, BCL-2, and MCL-1) were examined by Western blotting. BC-AE decreased cell viability after 24 hours via late apoptosis, while 72-hour exposure increased necrosis without further viability loss. Both BAX and MCL-1 protein levels increased in Caco-2 cells after 72 hours of BC-AE treatment, and miR-15b and miR-21 were upregulated, suggesting the involvement of a regulatory mechanism controlling cell survival. The obtained findings highlight the importance of considering both concentration and exposure duration when assessing biochar bioactivity.

Abstract: Environmental contaminants pose threats to various organisms and negatively impact the nervous, cardiovascular, immune, and reproductive systems. Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that are ubiquitous in the environment. Given that mixtures of environmental contaminants have the potential to exacerbate toxicity, we reviewed current literature on pesticides, microplastics, or metal exposure in combination with PFAS on vertebrates and invertebrates. The objectives were to evaluate the toxicological effects of mixtures of different pollutants (microplastics, pesticides and metal ions) with PFAS on aquatic organisms to better understand biological responses in animals. Based on our review, an increase in toxicity is observed in mixtures of pollutants, including enhanced oxidative stress, developmental abnormalities, impaired reproduction, metabolic disruption, altered gene expression, and changes in enzymatic activity; however, some antagonistic interactions were also reported, underscoring the complexity of mixture effects in real environments. A computational assessment demonstrates that PFOS can engage in intermolecular interactions with pesticides, microplastic monomers, and metals, suggesting chemical-level mechanisms that could modify toxicity or bioavailability. Future studies should focus on elucidating the mechanisms underlying these complex interactions, investigating effects at different trophic levels and in a broader range of species, including mammalian models, and considering chronic exposures and environmentally relevant mixtures.

Abstract: The rapid emergence of New Psychoactive Substances (NPS), particularly pyrrolidinophenone derivatives, poses a significant challenge for public health and forensic toxicology. While their neuropharmacological profiles as dopamine transporter inhibitors are well-documented, their cardiac toxicity remains poorly understood. This study employs a high-resolution New Approach Methodology (NAM) using zebrafish embryos to integrate neurobehavioral and cardiotoxic endpoints for comparative hazard prioritization. We evaluated nine pyrrolidine-containing cathinones, including α-PVP, MDPV, α-PiHP, MDPiHP, α-D2PV, 3-Cl-, 4-Cl-, and 3,4-Cl-α-PVP, as well as 4-F-3-Me-α-PVP, on locomotor activity and cardiac rhythmicity in zebrafish embryos using high-speed video microscopy and dynamic pixel analysis.. Across the series, compounds induced concentration-dependent negative chronotropy and, in most cases, locomotor suppression. Crucially, we identified a functional dissociation between atrial rate control and atrioventricular (AV) conduction. The 3,4-dichloro substitution (3,4-Cl-α-PVP) was the most potent inducer of negative chronotropy (EC₅₀ = 52.6 μM), whereas 4-Cl-α-PVP exhibited a distinct pro-arrhythmic liability, increasing the incidence of 2:1 AV block. Time-course locomotor profiling indicated that α-PVP and chlorinated analogs were among the most potent behavioral modifiers. Using a Functional Safety Index (AV block EC₅₀ / locomotor EC₅₀-like), we show that most compounds exhibit wide separations between neurobehavioral inhibition and severe conduction impairment, while specific substitutions—particularly para-chlorination—are associated with comparatively reduced safety margins. Overall, these data demonstrate that subtle structural changes within the pyrrolidinophenone scaffold can shape distinct arrhythmic phenotypes and functional safety profiles, supporting zebrafish-based integrated screening as a rapid platform for prioritizing emerging synthetic cathinones with disproportionate cardiac risk.

Abstract: The evolution of resistance in mosquitoes to conventional pesticides such as pyrethroids presents a challenge to vector control. Thus, alternative active ingredients for pesticides to manage pyrethroid resistant populations of mosquitoes are needed. The goal of this study was to evaluate the toxic and repellent efficacies of geraniol, a plant secondary metabolite, as a potential alternative for controlling pyrethroid-resistant Aedes aegypti. We found that addition of geraniol to rearing water of 1st instar larvae caused concentration-dependent mortality within 24 h in both strains. The resistance ratio of geraniol (2.8) was modest compared to that of cypermethrin (435.3). Topical application of geraniol to adult female mosquitoes caused dose-dependent mortality in both strains within 24 h. The resistance ratio of geraniol (1.1) was minimal compared to that for cypermethrin (457). In spatial repellency assays, geraniol repelled adult females from both strains in a dose-dependent manner. The repellency resistance ratio of geraniol (2.6) was modest compared to that for pyrethrum extract (>132). Our findings suggest that geraniol has potential use as a versatile chemical tool for controlling pyrethroid-resistant populations of Ae. aegypti.

Abstract: Intravenous lipid therapy (ILE) is used to treat neurotoxicosis in companion animals, but clinical evidence for in vivo xenobiotic partitioning and benefit remains limited. This study evaluated associations between the log n-octanol/water partition coefficient (log P), in vivo plasma partitioning, and early neurological outcome. In a case series from eight veterinary hospitals, dogs and cats with suspected neurotoxicosis received ILE; blood collected before and at the end of infusion was separated into lipid and aqueous fractions and analyzed by gas chromatography-mass spectrometry. Log P values were retrieved from PubChem. Outcome (improved vs not improved) was the change from baseline to 4- 6 h after ILE start. Thirty-four cases were analyzed (27 dogs, 7 cats; 17 xenobiotics). At end of infusion, lipid-phase concentrations exceeded aqueous concentrations in 28/34 cases, and log P did not correlate with the lipid-to-aqueous ratio. Improvement occurred in 14/34 animals and was associated with higher lipid-to-aqueous xenobiotic ratios (geometric mean ratio 5.7; 95% CI 1.73–19.05; P = 0.007). Overall, in vivo lipid sequestration was frequent and related to early improvement, whereas log P alone did not predict partitioning or outcome.

Abstract: Background Lipophilic environmental contaminants—including persistent organic pollutants (POPs), PFAS, PCBs, and PAHs - exert a long-term biological influence that cannot be explained by acute toxicity alone. Their extreme hydrophobicity drives high-affinity sequestration within lipid-rich tissues, such as adipose depots, myelin sheaths, and endocrine glands, creating "internal reservoirs" with biological half-lives measured in decades. These reservoirs fuel continuous, low-grade endogenous exposure and sequential absorption of hydrophilic species, persisting regardless of ongoing environmental contact. Scope of Review This article integrates toxicokinetic modeling with modern multi-omics evidence to update Zeliger’s model of lipophilicity-driven chronic disease. We examine how these diverse compounds activate a conserved set of biological injury pathways, regardless of their specific chemical structure. Specifically, we analyze the convergence of nuclear receptor disruption, mitochondrial dysfunction (amplified ROS production), calcium dysregulation, neuroimmune activation, and persistent epigenetic remodeling. Major Conclusions Lipophilic pollutants function as a unified category of systemic toxicants that reorganize cellular and metabolic systems. The identified mechanistic signatures provide a systems-level explanation for the epidemiological links between pollutant burdens and metabolic syndrome, cardiovascular morbidity, neurodegeneration, and cross-generational epigenetic effects. These findings validate the use of "total oxidative stress" as a predictor for non-communicable disease onset and support a paradigm shift toward mixture-based regulation and exposomic biomarkers for early detection.

Abstract: Background: Medicinal plants used in traditional Mexican medicine represent a valu-able source of bioactive compounds with potential anticancer activity. Beyond cyto-toxic potency, selectivity toward cancer cells over normal cells is a critical toxicologi-cal parameter for identifying safer therapeutic candidates. This study aimed to evalu-ate the selective cytotoxic and antiproliferative effects of extracts from four Mexican medicinal plants across human cancerous and non-cancerous cell lines. Methods: Hexane, acetone, and methanolic extracts from Semialarium mexicanum, Eryngium heterophyllum, Piper auritum, and Cochlospermum vitifolium were evaluated in a panel of human cancer cell lines and non-tumoral models, including primary human uterine fibroblasts (HUF). Cytotoxicity was assessed after 48 h of treatment using in-creasing extract concentrations, and selectivity indices were calculated. Cell cycle dis-tribution and nuclear morphology analyses were performed to explore antiprolifera-tive effects. Additionally, GC–MS-based chemical profiling was conducted on selected extracts to obtain a tentative characterization of major bioactive constituents. Results: The extracts exhibited differential cytotoxic profiles depending on plant spe-cies and solvent polarity. Semialarium mexicanum, particularly its hexane extract, showed the highest cytotoxic potency and selectivity toward HeLa cervical cancer cells, achieving selectivity indices higher than those observed for paclitaxel when compared with HUF cells. Hexane extracts of Semialarium mexicanum and Eryngium heterophyllum, were generally more active than polar extracts, whereas Piper auritum displayed limited cytotoxicity and Cochlospermum vitifolium showed moderate, sol-vent-dependent effects. Cell cycle perturbations and nuclear alterations supported an antiproliferative response. Chemical profiling suggested the presence of lipophilic triterpenoid-related compounds in non-polar extracts and phenolic constituents in polar fractions. Conclusions: These findings provide in vitro evidence of selective anticancer activity of Mexican medicinal plant extracts and establish a basis for future mechanistic stud-ies medicinal plant extracts and lay the groundwork for future mechanistic investigations.

Abstract:

Chronic kidney disease (CKD) is characterized by progressive glomerulosclerosis and interstitial fibrosis, ultimately leading to irreversible renal dysfunction. Tacrolimus, a calcineurin inhibitor widely used after kidney transplantation, is known to accelerate chronic renal injury, whereas everolimus has been introduced as a calcineurin inhibitor–sparing agent. However, their direct effects on renal fibrogenesis remain incompletely defined. In this study, we established a chronic renal failure model using 5/6 nephrectomized rats to evaluate tacrolimus-accelerated renal interstitial fibrosis and the impact of concomitant everolimus treatment. Low-dose tacrolimus (1 mg/kg every other day) administered for two weeks starting four weeks after nephrectomy markedly accelerated interstitial fibrotic progression, accompanied by histological deterioration and increased albuminuria. Co-administration of low-dose everolimus (1 mg/kg every other day) significantly attenuated tacrolimus-accelerated fibrosis and improved functional and structural renal parameters. Histological analyses demonstrated reduced interstitial fibrosis and glomerular alterations in the everolimus-treated group. Although α-smooth muscle actin expression was not significantly suppressed, everolimus restored autophagic activity, as indicated by normalization of the LC3-II/LC3-I ratio in both in vivo and in vitro experiments. These findings indicate that tacrolimus accelerates renal fibrogenesis in a remnant kidney model and that concomitant low-dose everolimus effectively mitigates this progression, providing a time- and cost-efficient experimental platform for evaluating antifibrotic strategies in CKD.

Abstract:

Microplastics (MPs) are synthetic solid polymers (1µm – 5mm) which are non-biodegradable. The toxicological effects of MPs have been well investigated, but research on how these particles affect PBMCs leaves much to be explored. Different concentrations 0.5 µg/ml, 5 µg/ml, 50 µg/ml, 500 µg/ml of PEG and manually grinded natural MPs were exposed to PBMCs in RPMI medium for 24 hours. Cell viability assay, Neutral Red phagocytosis assay, Griess colorimetric assay, Nitroblue Tetrazolium test was done to examine the cytotoxic effect of MPs on PBMCs. The present study results indicated that both natural MPs and Polyethylene Glycol (PEG) significantly reduced cell viability in a concentration-dependent manner. At highest concentrations, Natural MPs induced phagocytic activity of PBMCs. These MPs may act as stimulants to increase phagocytic activity. Regarding oxidative stress, Natural MPs exposure with PBMCs showed a significant increase in ROS production, whereas PEG exposure didn’t induce notable ROS production. NO production levels remained unchanged in PBMCs after exposure to both PEG and Natural MPs, showing that under the tested conditions, neither treatment significantly influenced the NO-mediated inflammatory pathways. In summary, this present study showed that MPs exposure to humans can impair cell viability, induce phagocytosis and induce ROS production without altering the NO mediated inflammatory pathways.

Abstract: External causes of death contribute to over four million annual global fatalities, with drug use representing a significant risk factor. However, the true national impact and regional variations of psychoactive substance use in these deaths remains unde-fined in Brazil. To address this critical knowledge gap, this pioneering four-region study sought to elucidate the influence of alcohol and drug use on external cause mor-tality. We collected post-mortem blood from 3,577 victims of violent death across four distinct Brazilian regions using a standardized protocol to identify alcohol, illicit drugs, and psychoactive medicines. Analysis revealed a predominantly male cohort (89.7%; 56.0% aged 30 years or more), with homicide as the primary manner of death (67.3%). Critically, over half of the victims (53.0%) were positive for at least one psy-choactive substance prior to death, most commonly cocaine (29.6%) and alcohol (27.7%). Substance consumption was highest among homicide victims (55.7%), pre-dominantly cocaine (36.0%), and in self-harm cases (26.4%), which showed high ben-zodiazepine rates (20.0%). Consumption patterns varied regionally: alcohol-related deaths were more common in the Northeast, drug-only deaths concentrated in the Southeast and North, and the South showed a higher prevalence of alcohol use versus drug use. This widespread, regionally heterogeneous prevalence underscores the ur-gent need for targeted, region-specific interventions. By critically linking psychoactive substance use to various modes of violent death, these data provide crucial forensic and public health insights to inform tailored preventive strategies.

Abstract: Small plastics polymers have the potential to bioaccumulate in tissues and initiate toxicity, raising concerns about the long-term impacts towards filter-feeders such as freshwater mussels. The purpose of this study was to examine the toxicity of two common plastic polymers (polyvinyl chloride-PVC; polyethylene terephthalate-PET) and the plasticizer dibutylphthalate (DBP) to quagga mussels Dreissena bugensis. Mussels were exposed to 5, 50 and 100 µg/L of the above compounds for 96h at 15oC. They were then analyzed for total plastic accumulation, esterase, peroxidase, lipids and protein aggregation in the soft tissues. The data revealed that DBP reduced survival at concentrations > 5 µg/L and all died at 100 µg/L. An estimated bioavailability factor of 90, 40 and 1580 for PVC, PET and DBP was determined. These differences could be explained by particle size and form for PVC (0.5 µm fiber) and PET (2 µm diameter). DBP tissue levels were also detected in mussels exposed to PVC and PET suggesting its presence in plastics. Esterase activity was strongly increased in DBP (ester)-treated mussels and was slightly decreased in mussels exposed to ester-containing PET. The biomarker data also revealed an increase in lipids, peroxidase and protein aggregation in a concentration-dependent manner. It is concluded that these compounds are bioavailable to mussels and the changes in esterase activity could be a factor leading to oxidative stress and protein aggregation in mussel tissues.

Abstract:

Persistent environmental pollutants such as per- and poly-fluoroalkyl substances (PFAS) have been associated with a wide range of toxic effects, including cancer. There are over 12,000 PFAS compounds, which may act as carcinogens individually or in combinations. Therefore, efficient in vivo models of carcinogenicity are needed for evaluating environmental contaminant compounds and chemical mixtures. Here, we use the larval zebrafish xenograft assay to identify tumor growth activity of perfluorooctanesulfonic acid (PFOS), a known carcinogenic PFAS. Dose response curves for PFOS exposure were used to identify the Maximum Tolerated Concentration (MTC) and Lethal Concentration causing 50% death (LC50) under xenograft conditions. Zebrafish xenografts were established by injecting fluorescently labeled kidney cancer cells into the embryonic body cavity near the developing kidney, followed by treatment with PFOS at a concentration of 5%, 10% and 20% of the MTC. When treated with PFOS, zebrafish xenografts using renal cell carcinoma (ACHN) cells and clear renal cell carcinoma (Caki-1) cells show dose-dependent changes in tumor area. This study is the first to directly show cancer-promoting activity of a PFAS, using a rapid in vivo zebrafish xenograft assay, and demonstrates the utility of this model for validation of predicted cancer-promoting properties of environmental contaminants.

Abstract: Niclosamide has been the primary molluscicide for schistosomiasis control for over 50 years, but it poses significant threats to non-target large freshwater mollusks. Cipangopaludina cahayensis, a dominant species in East Asian schistosomiasis-endemic regions, was chronically exposed under environmentally relevant concentrations of niclosamide using a mesocosm approach to assess its toxic effects. Digestive glands accumulated more niclosamide than foot tissues. Prolonged exposure disrupted metabolic processes in the digestive glands, leading to tubular atrophy, inflammatory responses, and nutrient depletion. In the foot, niclosamide caused structural damage to both tissue and muscle fibers, resulting in reduced mobility. Furthermore, niclosamide impaired nutritional coupling between the digestive glands and foot, exacerbating motor dysfunction in the foot. Persistent niclosamide exposure destabilized molluscan trophic-level population dynamics, ultimately triggering multi-faceted ecological disturbances, including a decline in ecosystem resilience and disruption of key ecological functions. Our findings underscore the significant toxicological risks that niclosamide poses to freshwater mollusks and highlight the urgent need for the development of ecologically sound usage guidelines to minimize off-target effects.

Abstract: Cystic fibrosis (CF) airway mucus is thick and sticky, which makes it hard for nanoparticles to move and deliver drugs effectively. In this study, degradable PLGA nanoparticles were coated with polyethylene glycol (PEG) of different molecular weights (2, 5, and 10 kDa) to test their movement and depth of penetration in CF-like mucus. The nanoparticles had a uniform size of 150 ± 10 nm and were measured using fluorescence recovery after photobleaching (FRAP) and confocal imaging. The PEG (5 kDa) coating showed the best results, with a diffusion rate of 1.45 ± 0.12 µm²/s, about 3.8 times higher than that of uncoated particles. In a 6-hour test, the particles moved over 70% deeper into the mucus and showed much higher uptake by airway cells (P < 0.01). These results show that medium-length PEG chains reduce mucus adhesion and help nanoparticles move more easily through dense airway mucus. This work provides a practical way to improve drug carriers for CF and other lung diseases with mucus blockage.