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Keywords = toxicity determinants

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15 pages, 4280 KB  
Review
Mechanisms of Microplastic Effects on Carbon and Nitrogen Cycling in Aquatic and Terrestrial Ecosystems
by Xintong Zhang, Yuxiao Chen, Chia Min Ho, Weiying Feng and Xuezheng Yu
Toxics 2026, 14(7), 551; https://doi.org/10.3390/toxics14070551 (registering DOI) - 24 Jun 2026
Abstract
An emerging environmental pollutant, microplastics have garnered global attention due to their widespread presence in soil and aquatic ecosystems. Early research primarily treated microplastics as single pollutants, focusing on their individual toxic effects. However, microplastics in the environment exist as a complex mixture, [...] Read more.
An emerging environmental pollutant, microplastics have garnered global attention due to their widespread presence in soil and aquatic ecosystems. Early research primarily treated microplastics as single pollutants, focusing on their individual toxic effects. However, microplastics in the environment exist as a complex mixture, comprising various polymer types, sizes, shapes, and aging states. This diversity influences how microplastics regulate ecosystem carbon and nitrogen cycles and intervene through pathways such as direct carbon input, physical disturbance, microbial community restructuring, and coupled effects. This paper systematically reviews the characteristics of microplastic diversity and its mechanisms influencing carbon and nitrogen cycles: the chemical structure of polymers determines bioavailability and degradation rate, with biodegradable plastics altering carbon and nitrogen transformations more significantly than conventional plastics; microplastics of different sizes affect nitrogen transformation dynamics by modulating specific surface area and microbial colonization, with small-sized biodegradable microplastics particularly inhibiting plant nitrogen uptake; aging modifies surface properties and dissolved organic carbon release, thereby enhancing their role in promoting greenhouse gas emissions. Existing studies are largely confined to short-term laboratory simulations, leaving a gap in understanding the comprehensive effects of microplastic diversity under long-term, field conditions. Future research should focus on standardized methods and long-term experiments with multi-factor coupling to provide a scientific basis for ecological risk assessment of microplastic pollution. Full article
(This article belongs to the Section Ecotoxicology)
19 pages, 997 KB  
Article
Spatiotemporal Characteristics and Quantitative Source Apportionment of Potentially Toxic Elements in the Lower Reaches of the Yellow River Based on a PMF Model
by Duohui Zhao, Wei Zhang, Anfu Zhang, Liang Yin, Bin Yang and Lei Song
Water 2026, 18(13), 1545; https://doi.org/10.3390/w18131545 (registering DOI) - 24 Jun 2026
Abstract
The sources of potentially toxic elements (PTEs) in the lower reaches of the Yellow River (LYR) remain poorly understood due to intensive human activities in this region. To elucidate the spatiotemporal distribution characteristics and sources of PTEs, water samples were collected from both [...] Read more.
The sources of potentially toxic elements (PTEs) in the lower reaches of the Yellow River (LYR) remain poorly understood due to intensive human activities in this region. To elucidate the spatiotemporal distribution characteristics and sources of PTEs, water samples were collected from both mainstream and tributary sites during the dry season (DS) and flood season (FS). Concentrations of eight PTEs (Fe, Mn, Cu, Zn, Pb, As, Cr, and Hg) were determined. The single-factor pollution index, Nemerow comprehensive pollution index, statistical techniques, and the positive matrix factorization (PMF) receptor model were jointly employed to evaluate PTEs pollution levels and quantitatively apportion its sources. The results showed that PTEs concentrations in the mainstream were significantly higher than those in the tributaries, with Fe and Mn being the primary contaminants exceeding standards. During the DS, the mean concentrations of Fe and Mn were 1.33 mg/L and 0.34 mg/L, with exceedance rates of 100% and 84.2%, respectively. In contrast, both concentrations declined markedly in the FS (Fe: 0.27 mg/L; Mn: 0.112 mg/L). The PMF model identified three sources in the DS, with contribution rates of 42.1% (geogenic background and domestic sewage), 32.4% (industrial wastewater), and 25.5% (agricultural sources). In the FS, two sources were resolved, namely a mixture of non-point source pollution and domestic sewage (64.3%) and a mixture of geogenic background and industrial wastewater (35.7%). The pronounced increase in non-point source contribution during the FS highlights the role of rainfall runoff in driving pollutant input. This study provides a scientific basis for PTEs pollution control in the LYR. Full article
18 pages, 10002 KB  
Article
A Phase I Trial of Iopofosine I 131 and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma
by Sikander Ailawadhi, Jennifer L. Peterson, Kate Oliver, Jarrod Longcor and Natalie Callander
Cancers 2026, 18(13), 2044; https://doi.org/10.3390/cancers18132044 (registering DOI) - 24 Jun 2026
Abstract
Background/Objectives: Patients with relapsed/refractory multiple myeloma (RRMM) have poor survival outcomes and limited treatment options. The increasing utilization of multiagent therapies for earlier lines of treatment and novel drug classes including BCMA-targeting agents in subsequent lines of therapy has created a need [...] Read more.
Background/Objectives: Patients with relapsed/refractory multiple myeloma (RRMM) have poor survival outcomes and limited treatment options. The increasing utilization of multiagent therapies for earlier lines of treatment and novel drug classes including BCMA-targeting agents in subsequent lines of therapy has created a need for innovative treatment platforms in patients who have relapsed after or are refractory to these current standard-of-care approaches. Iopofosine I 131 is a 131iodide (131I)–phospholipid conjugate that exploits the selective uptake and retention of phospholipid ethers through lipid rafts to facilitate tumor delivery of 131I. Methods: The objective of this phase 1 dose-escalation study was to assess the safety and tolerability of single and fractionated dose schedules of iopofosine I 131 + low-dose dexamethasone in heavily pretreated patients with RRMM. Results: The most common AEs overall were cytopenias, notably thrombocytopenia (93.5%), lymphopenia (74.2%), anemia (71%), leukopenia (61.3%), and neutropenia (58.1%). All patients experiencing hematologic adverse events recovered from those events with median time of recovery 21 days post-nadir. Nonhematologic adverse events were mostly limited to Grade 1 and 2. Dose-limiting toxicities included four Grade 4 thrombocytopenia events lasting longer than 7 days, one Grade 4 neutropenia, and one Grade 3 insomnia. The DMC determined 31.25 mCi/m2 was the maximum tolerated dose in the single-dose group, and 20 mCi/m2 × 2 doses was the maximum tolerated dose in the fractionated-dose group. For patients monitored through 85 days following the first infusion, 22 of 26 (84.6%) achieved stable disease after treatment, and 4 of 26 (15.4%) achieved a partial response. Conclusions: A favorable safety and tolerability profile and preliminary clinical activity support further development of iopofosine I 131 in RRMM. Full article
(This article belongs to the Special Issue Clinical Trials and Translational Research in Multiple Myeloma)
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15 pages, 1297 KB  
Article
Ecological and Health Risk Assessment of Potentially Toxic Elements in the Small Wetlands in the Baghrash Lake Basin, China
by Mamattursun Eziz and Mireguli Ainiwaer
Toxics 2026, 14(7), 547; https://doi.org/10.3390/toxics14070547 (registering DOI) - 24 Jun 2026
Abstract
Despite their size, small wetlands play a vital role in maintaining ecosystem stability. To clarify the pollution levels as well as potential ecological and health risks of potentially toxic elements (PTEs) in small wetlands, 85 water samples were collected from small wetlands in [...] Read more.
Despite their size, small wetlands play a vital role in maintaining ecosystem stability. To clarify the pollution levels as well as potential ecological and health risks of potentially toxic elements (PTEs) in small wetlands, 85 water samples were collected from small wetlands in the Baghrash Lake Basin (BLB) of China, and six PTEs (As, Cd, Cu, Hg, Pb, and Zn) were determined for their contents. The Nemerow integrated pollution index (NPI) was adopted to evaluate PTE pollution levels. The ecological risk index (RI) and USEPA health risk assessment model were further applied to quantify potential ecological and health risks of PTEs, respectively. The results revealed that PTEs in small wetlands showed a slight pollution level, with an average NPI value of 0.73. Meanwhile, the integrated ecological risk index of PTEs showed a low ecological risk level, with an average RI value of 23.041. Health risk assessment results demonstrated that the non-carcinogenic risk of PTEs in small wetlands remained at a negligible level, while the carcinogenic risk stayed within acceptable limits for both local population groups: children and adults. Among all detected PTEs, Hg was identified as the primary pollutant and major ecological risk factor, while As posed the highest relative potential health risk while overall risks remained acceptable. The findings of this study can provide a scientific basis for the environmental protection of small wetlands in the BLB. Full article
(This article belongs to the Special Issue Environmental Contaminants and Human Health—2nd Edition)
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12 pages, 472 KB  
Article
Sensitivity of Urinary Toxicant Co-Exposure Patterns to Demographic Adjustment and Marker Type: A Methodological Analysis
by Basant K. Puri and Jean A. Monro
Toxics 2026, 14(7), 546; https://doi.org/10.3390/toxics14070546 (registering DOI) - 23 Jun 2026
Abstract
Patients presenting with conditions attributed to environmental exposures face complex, multi-toxicant burdens, yet the stability of multivariate toxicant patterns under demographic adjustment remains poorly evaluated. This study assessed the sensitivity of principal component analysis (PCA) structures to demographic confounding and variable composition in [...] Read more.
Patients presenting with conditions attributed to environmental exposures face complex, multi-toxicant burdens, yet the stability of multivariate toxicant patterns under demographic adjustment remains poorly evaluated. This study assessed the sensitivity of principal component analysis (PCA) structures to demographic confounding and variable composition in 551 patients (aged <1–86 years) with environmentally related conditions. Nine urinary biomarkers were analysed using PCA with Varimax and Promax rotation on both raw data and residuals adjusted for age and sex. Among the identified patterns, the solvent/industrial cluster (xylene and styrene metabolites) was the most stable, persisting across both raw and residual analyses regardless of rotation method. However, overall component structures were sensitive to preprocessing: the clustering pattern of the herbicide 2,4-dichlorophenoxyacetic acid shifted markedly after demographic adjustment, illustrating indirect confounding whereby demographic effects on co-variables altered apparent biomarker associations. Notably, inclusion of an endogenous mitochondrial marker (tiglylglycine) alongside exogenous toxicant biomarkers produced Heywood cases (loadings > 1), violating factor analysis assumptions and indicating that mixing exposure and response variables destabilises the model. Cumulative variance explained was modest, consistent with the weak inter-biomarker correlations observed (KMO ≈ 0.52). These findings do not support the identification of robust, demographically stable clustering patterns in this cohort. Instead, they demonstrate that PCA-derived structures in heterogeneous clinical data are vulnerable to demographic confounding, variable selection and marker type, and caution against interpreting transient clustering patterns as definitive exposure signatures without rigorous validation. It should be noted that the absence of a non-clinical matched control group means that whether the identified co-exposure signatures are distinctive to symptomatic patients or reflective of general population exposure patterns cannot be determined; future studies should incorporate matched controls to address this directly. Full article
(This article belongs to the Section Human Toxicology and Epidemiology)
24 pages, 1117 KB  
Review
Environmental Behavior, Toxicological Pathways, and Risk Assessment of Polycyclic Aromatic Hydrocarbons (PAHs): From Molecular Structure to Human Health
by Joanna Harasym and Edyta Nizio
Molecules 2026, 31(13), 2211; https://doi.org/10.3390/molecules31132211 (registering DOI) - 23 Jun 2026
Abstract
Polycyclic aromatic hydrocarbons (PAHs) represent a major class of ubiquitous environmental pollutants, posing significant risks to ecosystems and human health due to their persistence, toxicity, and potential for bioaccumulation. This review provides a comprehensive synthesis of current scientific knowledge on PAHs, integrating insights [...] Read more.
Polycyclic aromatic hydrocarbons (PAHs) represent a major class of ubiquitous environmental pollutants, posing significant risks to ecosystems and human health due to their persistence, toxicity, and potential for bioaccumulation. This review provides a comprehensive synthesis of current scientific knowledge on PAHs, integrating insights from chemical kinetics, environmental fate, and toxicological mechanisms. The fundamental structural chemistry of PAHs and its direct influence on their physicochemical properties and environmental properties are discussed. The major anthropogenic and natural sources of PAHs are detailed, alongside the chemical kinetics behind their formation during incomplete combustion and their transformation in environmental media. Unlike previous reviews that address PAH sources, remediation, or health effects as separate topics, this review uniquely traces the mechanistic continuum from molecular formation kinetics through physicochemical partitioning and environmental transport to toxicological endpoints, providing a causally linked framework for understanding how structural properties ultimately determine biological outcomes. A central focus is placed on the environmental fate and transport of PAHs across atmospheric, aquatic, and terrestrial compartments, highlighting processes such as gas–particle partitioning, sediment accumulation, and long-range transport. The review further elucidates the complex toxicological pathways of PAHs, including metabolic activation to reactive intermediates, DNA adduct formation, oxidative stress, and their roles in carcinogenesis and other systemic health effects. The analysis reveals strong scientific consensus on the carcinogenic mechanism of parent PAHs via CYP450-mediated metabolic activation to diol-epoxide intermediates while identifying critical areas of uncertainty: the current regulatory framework based on 16 priority PAHs underestimates total carcinogenic risk by a factor of 2–5, mixture toxicology remains poorly characterized, and dose–response relationships for non-cancer endpoints (cardiovascular, neurodevelopmental, immunotoxic) lack the quantitative data needed for robust risk assessment. Finally, human exposure pathways and health risk characterization approaches are discussed, highlighting the need for cumulative, mixture-based assessment frameworks. Full article
(This article belongs to the Special Issue Featured Reviews in Organic Chemistry 2025–2026)
2 pages, 129 KB  
Abstract
Multisubstance Screening Supports a High-Throughput Zebrafish Thigmotaxis Assay for One Health-Oriented Neurotoxicity Assessment
by Monica Torres-Ruiz, María Muñoz-Palencia, Laura Sánchez-Ramos, Ana I. Cañas-Portilla and Antonio de la Vieja
Proceedings 2026, 146(1), 107; https://doi.org/10.3390/proceedings2026146107 (registering DOI) - 22 Jun 2026
Viewed by 18
Abstract
Introduction: Aquatic contaminants can alter fish behavior before overt toxicity becomes evident, making neurobehavioral endpoints relevant for ecosystem protection and for hazard prioritization within a One Health framework. We recently developed a high-throughput visual-acoustic zebrafish larval thigmotaxis assay in which edge preference is [...] Read more.
Introduction: Aquatic contaminants can alter fish behavior before overt toxicity becomes evident, making neurobehavioral endpoints relevant for ecosystem protection and for hazard prioritization within a One Health framework. We recently developed a high-throughput visual-acoustic zebrafish larval thigmotaxis assay in which edge preference is interpreted as an anxiety-like behavioral endpoint, thereby adding spatial phenotyping beyond conventional locomotion metrics. Objective: To evaluate assay performance in a multisubstance screening challenge and determine whether it can discriminate distinct behavioral fingerprints without prior knowledge of chemical identity. Methodology: Zebrafish larvae were exposed for 1 h at 120 hpf. For each substance, 24 larvae were tested per condition, with six concentrations per substance, plus positive and negative controls. Larvae were challenged using alternating light/dark and tapping/quiet paradigms. The primary endpoint was the percentage of time spent at the edge as a proxy for anxiety-like behavior, while total distance and mean total velocity when moving were used as contextual locomotor metrics; edge distance and edge velocity were used as supportive spatial metrics. Data from 37 substances were analyzed through a standardized automated workflow. Results: Controls performed as expected and supported assay stability across runs. The chemical screening revealed heterogeneous but reproducible behavioral fingerprints. Seven substances produced weak/minimal acute responses, ten showed predominantly suppressive profiles, three predominantly activating profiles, nine showed prominent thigmotaxis-specific anxiety-like signals not explained by locomotion alone, and eight displayed mixed or stimulus-dependent patterns, including non-monotonic responses. Several substances altered edge preference while distance and velocity changed less, differently, or in the opposite direction, indicating behavioral reorganization rather than simple hypo- or hyperactivity. The multi-stimulus design was critical because some effects were evident only under specific sensory contexts. Conclusions: The multisubstance challenge supports the discriminatory capacity, robustness, and added value of the assay for high-throughput neurobehavioral screening. By capturing anxiety-like behavior through thigmotaxis and complementing it with locomotor context, the method improves phenotypic resolution for aquatic pollution assessment and offers a sensitive fish-based NAM to prioritize chemicals of concern for both environmental and human health-oriented testing strategies. Full article
(This article belongs to the Proceedings of The XI Iberian Congress of Ichthyology)
20 pages, 9222 KB  
Article
Integrated Assessment of Potentially Toxic Elements in Soils and Irrigation Water and Human Health Risk in a Gold Mining-Impacted Area of Southern Ecuador
by Juan González-Menéndez, Carlos Hugo Bustamante-Torres, Bryan Salgado-Almeida, Giannella Muriel-Granda, Samantha Jiménez-Oyola and Kenny Escobar-Segovia
Resources 2026, 15(6), 81; https://doi.org/10.3390/resources15060081 (registering DOI) - 22 Jun 2026
Viewed by 187
Abstract
Areas where mining activities overlap with agricultural production may promote the mobilization of potentially toxic elements (PTEs) into soils and water resources, thereby creating exposure pathways for populations living or working in these environments. This study analyzes the concentration of PTEs in agricultural [...] Read more.
Areas where mining activities overlap with agricultural production may promote the mobilization of potentially toxic elements (PTEs) into soils and water resources, thereby creating exposure pathways for populations living or working in these environments. This study analyzes the concentration of PTEs in agricultural soils and irrigation water from Santa Rosa, southern Ecuador, and assesses the associated health risks for exposed agricultural workers. For this purpose, 35 soil samples were collected from farms and 12 water samples from the irrigation canal during the dry season of 2025. The concentration of PTEs in soil and water was determined using X-ray fluorescence (XRF) and inductively coupled plasma mass spectrometry (ICP-MS), respectively. The PTE concentration in both matrices was compared with the maximum permissible limits (MPL) established by Ecuadorian regulations. Non-carcinogenic hazard indices (HI) and carcinogenic risk (TCR) were estimated following the U.S. EPA methodology. In soil, As and Cr were the PTEs of greatest concern, exceeding the MPL in 93% of the samples and by up to 4.4 and 2.4 times, respectively, while in water, all PTEs were below the MPL. Non-carcinogenic risk was below the recommended limit for soil and water (HIsoil = 3.00 × 10−2 and HIwater = 2.00 × 10−3), with As as the dominant contributor. Cancer risk was tolerable in soil (TCRsoil = 4.34 × 10−5), while in water it remained at a low level (TCRwater = 1.65 × 10−6). These findings identify As and Cr as priority contaminants and support targeted monitoring and source-control measures in mining-influenced agricultural areas. Overall, by integrating agricultural soil and irrigation water quality with an occupational health risk assessment in Santa Rosa, this study contributes evidence to support future research in mining–agriculture coexistence areas. Full article
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20 pages, 4545 KB  
Article
Preventing Pesticide Toxicity Risk Through Self-Reported Practices in Children of Farming Communities: A Social Practice Theory Perspective
by Nuraeni Nuraeni, Herdis Herdiansyah, Fatmah Fatmah, Haruki Agustina and Rully Yusuf
J. Xenobiot. 2026, 16(3), 117; https://doi.org/10.3390/jox16030117 (registering DOI) - 22 Jun 2026
Viewed by 150
Abstract
This study analyzes the determinants of self-reported behaviours and perceptions associated with pesticide toxicity risk in children using the Social Practice Theory framework, linking individual factors and agricultural practices to understand vulnerability and prevention opportunities. This research was conducted in Pattapang Village, Tinggimoncong [...] Read more.
This study analyzes the determinants of self-reported behaviours and perceptions associated with pesticide toxicity risk in children using the Social Practice Theory framework, linking individual factors and agricultural practices to understand vulnerability and prevention opportunities. This research was conducted in Pattapang Village, Tinggimoncong District, Gowa Regency, South Sulawesi Province, Indonesia. To examine the relationship between pesticide use patterns, social norms, competence, material, and individual aspects and the risk of sensitive toxicity in children, data were analyzed using structural equation modeling-partial least squares (SEM-PLS) with bootstrapping resampling. Pesticide use patterns had a significant negative effect on toxicity risk. Competence was the strongest predictor of pesticide use patterns, followed by materials and short-term goals. Personal values dominate personal norms and long-term goals, while social norms only influence personal norms. Self-efficacy, personal norms, and long-term goals showed no significant effects. The novelty of this research lies in the integration of a socio-ecological approach with individual psychological factors in a comprehensive structural model that explains the complex mechanisms of children’s protective behavior formation from pesticide toxicity, identifying that personal values—not personal norms or self-efficacy—are the most effective leverage points for farmer behavior change interventions. Full article
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19 pages, 1099 KB  
Article
Adsorption of Polycyclic Aromatic Hydrocarbons by Synthesized Organo-Mineral and Bio-Organo-Mineral Complexes
by Tamara Dudnikova, Leonid Perelomov, Maria Gertsen, Marina Burachevskaya, Svetlana Kozmenko, Saglara Mandzhieva, Irina Perelomova, Vyacheslav Arlyapov and Tatiana Minkina
Environments 2026, 13(6), 354; https://doi.org/10.3390/environments13060354 (registering DOI) - 20 Jun 2026
Viewed by 353
Abstract
Environmental pollution by polycyclic aromatic hydrocarbons (PAHs) is a serious environmental problem. One of the effective methods of cleaning the environment from these toxicants is the use of sorbents based on clay minerals. Special organo-mineral, bio-mineral and bio-organo-mineral complexes were obtained. Organo-mineral complexes [...] Read more.
Environmental pollution by polycyclic aromatic hydrocarbons (PAHs) is a serious environmental problem. One of the effective methods of cleaning the environment from these toxicants is the use of sorbents based on clay minerals. Special organo-mineral, bio-mineral and bio-organo-mineral complexes were obtained. Organo-mineral complexes (organoclays) were synthesized on the basis of Na-bentonite and anionic, amphoteric and nonionic surfactants. Bio-mineral and bio-organo-mineral complexes were produced by inoculating bentonite and organoclays with a consortium of bacteria. The adsorption characteristics of the complexes to benzopyrene and naphthalene were studied. Modification of bentonite with various types of surfactants leads to a significant increase in the percentage adsorption of both benzopyrene and naphthalene, with benzopyrene being more so. All bio-organo-mineral complexes adsorb more benzopyrene than pure bentonite and the bentonite + bacteria complex. In most cases, this pattern is also characteristic of naphthalene adsorption. Organoclay complexes with bacteria adsorb PAHs in greater quantities than organoclays, typically at the average concentrations of benzopyrene and naphthalene used (30–60 μg mL−1) and when modified with individual surfactants. Based on the determination coefficients, the adsorption of benzopyrene and naphthalene by all studied sorbents is best described by the Langmuir equation. The maximum (limiting) adsorption of benzopyrene by all organo-mineral complexes (organoclays) exceeds the maximum adsorption of benzopyrene by bentonite. Modification of bentonite with surfactants may not change, decrease, or increase the maximum adsorption of naphthalene compared to the original bentonite, depending on the surfactant used. Colonization of the organoclay surface by bacteria, with rare exceptions, results in a decrease in the maximum adsorption values of benzopyrene and naphthalene compared to organoclay, or has no effect at all. Full article
(This article belongs to the Section Environmental Pollution, Toxicology and Restoration)
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21 pages, 8004 KB  
Article
Comparative Transcriptomic Analysis of Detoxification Enzyme Gene Families in Parent and Offspring Riptortus pedestris After Sublethal Thiamethoxam Treatment
by Sizhu Zhao, Zijie Wang, Simeng Chen, Ruirui Li, Zhengxiao Du, Xing Huang, Haibin Yuan, Shusen Shi, Yuxin Zhou and Yu Gao
Insects 2026, 17(6), 648; https://doi.org/10.3390/insects17060648 (registering DOI) - 19 Jun 2026
Viewed by 199
Abstract
Thiamethoxam is the main neonicotinoid insecticide used for controlling Riptortus pedestris (Fabricius) (Hemiptera: Alydidae). However, sublethal concentration stress may induce intergenerational transcriptional memory, leading to transcriptional patterns that may contribute to the intergenerational accumulation of metabolic tolerance, and evaluating only the toxicity of [...] Read more.
Thiamethoxam is the main neonicotinoid insecticide used for controlling Riptortus pedestris (Fabricius) (Hemiptera: Alydidae). However, sublethal concentration stress may induce intergenerational transcriptional memory, leading to transcriptional patterns that may contribute to the intergenerational accumulation of metabolic tolerance, and evaluating only the toxicity of the current generation would underestimate the long-term risk. Therefore, this study investigated the effect of parental exposure on the expression of detoxification enzyme genes in offspring. Using transcriptome sequencing, we systematically identified three detoxification enzyme gene families (cytochrome P450 monooxygenases (CYPs), carboxylesterases (CCEs), and glutathione S-transferases (GSTs)) in R. pedestris and compared their differential expression patterns between the parental and filial generations after thiamethoxam treatment at three sublethal concentrations (LC10, LC30, and LC50). In the parental generation, a Theta family GST was consistently upregulated, while in the filial generation, detoxification genes were predominantly downregulated, and the genes upregulated in the parents were not also upregulated in the offspring. Comparisons of parents and offspring at the same concentration revealed that the medium concentration induced the highest number of intergenerationally upregulated genes, exhibiting a non-linear response pattern. These results indicate that parental exposure to sublethal thiamethoxam leaves an intergenerational transcriptional imprint in the offspring, and the transmission pattern involves transcriptional reprogramming rather than simple replication of the parental response, the mechanism of which remains to be determined. This study provides transcriptomic evidence for understanding the metabolic adaptation and intergenerational resistance evolution of R. pedestris to thiamethoxam, offering important reference value for field resistance monitoring and rational insecticide application. Full article
(This article belongs to the Special Issue Advances in the Effects of Insecticides on Pests)
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15 pages, 16455 KB  
Article
Telomere-Associated Proliferative Capacity in Expandable Porcine Hepatocyte-like Progenitor Cells
by Sun A Ock, Yeongji Kim, Imran Ullah, Young-Im Kim, Ran Lee, Keon Bong Oh, Seongsoo Hwang and Juyoung Lee
Biology 2026, 15(12), 958; https://doi.org/10.3390/biology15120958 (registering DOI) - 18 Jun 2026
Viewed by 140
Abstract
Primary hepatocytes are limited by poor proliferative capacity and a finite replicative lifespan, restricting their utility in long-term in vitro studies. Here, we report the generation of expandable hepatocyte-like progenitor cells from GGTA1 knockout pigs, a large-animal model with reduced immunogenicity. Porcine fibroblasts [...] Read more.
Primary hepatocytes are limited by poor proliferative capacity and a finite replicative lifespan, restricting their utility in long-term in vitro studies. Here, we report the generation of expandable hepatocyte-like progenitor cells from GGTA1 knockout pigs, a large-animal model with reduced immunogenicity. Porcine fibroblasts were directly reprogrammed using a non-integrative episomal system encoding hepatic transcription factors, enabling stable lineage conversion without genomic integration. A simplified two-vector configuration combined with codon optimization enabled evaluation of vector-dependent effects while maintaining genomic safety without viral integration. The resulting cells exhibited hepatocyte-like morphology and gene expression, and transcriptomic analysis revealed a progressive shift toward liver-associated profiles during extended culture. Chromosomal analysis revealed vector-dependent differences in genomic stability, with codon-optimized cells showing increased aneuploidy, indicating a trade-off between proliferative capacity and genomic integrity. The cells also demonstrated sustained proliferative capacity, supported by maintenance of telomere length, increased expression of TERT and MYC, and reduced CDKN1A levels. Importantly, sustained proliferation was supported by complementary evidence from chromosomal and telomeric analyses. Although chromosomal alterations were observed during long-term culture, their biological significance remains to be fully determined. These cells partially recapitulate hepatocyte functions and provide a renewable in vitro system for studies of hepatic biology, proliferation, drug metabolism, toxicity, and repeated in vitro applications. Full article
(This article belongs to the Section Biotechnology)
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22 pages, 14729 KB  
Article
Metabolic Mechanisms of Hexavalent Chromium-Induced Splenic Immune Injury via Oxidative Stress and Ferroptosis Pathways in New Zealand Rabbits
by Junzhao Yuan, Jiaqi Zhang, Jinxing Song, Lingling Liu, Hang Liu, Shuangxing Jin and Xiaoli Ren
Metabolites 2026, 16(6), 430; https://doi.org/10.3390/metabo16060430 (registering DOI) - 18 Jun 2026
Viewed by 212
Abstract
Background: Hexavalent chromium (Cr(VI)) is a widespread environmental toxic heavy metal with strong oxidative properties; however, its immunotoxicity and metabolic mechanisms in rabbit spleen remain largely unclear. Methods: In this study, New Zealand rabbits were exposed to 0, 12.5, 25, and [...] Read more.
Background: Hexavalent chromium (Cr(VI)) is a widespread environmental toxic heavy metal with strong oxidative properties; however, its immunotoxicity and metabolic mechanisms in rabbit spleen remain largely unclear. Methods: In this study, New Zealand rabbits were exposed to 0, 12.5, 25, and 50 mg/L Cr(VI) (as potassium dichromate, K2Cr2O7) via drinking water for four weeks to investigate splenic damage and the underlying molecular pathways. Spleen pathological injury was evaluated by hematoxylin and eosin (H&E) staining, and the distribution of T cells, B cells, and macrophages was assessed by immunohistochemistry. Antioxidant enzyme activities and antioxidant substance levels were determined using ELISA, and the relative mRNA expression of immune factor genes, antioxidant-related genes, and ferroptosis-related genes was quantified by quantitative real-time PCR (qRT-PCR). In addition, the distribution of iron in splenic tissue was detected by enhanced Prussian blue staining. Results: Our results demonstrate that high-dose Cr(VI) significantly inhibited body weight gain, induced lymphocyte atrophy, vacuolization, and widening of intercellular spaces in the splenic white pulp. Furthermore, Cr(VI) reduced T and B lymphocyte populations, promoted macrophage infiltration and inflammatory cytokine gene expression in a concentration-dependent manner, impaired total antioxidant capacity, and led to a decrease in glutathione (GSH) levels in the spleen. Additionally, Cr(VI) exposure increased iron accumulation, activated the ACSL4–NOX lipid peroxidation cascade, and downregulated GPX4 expression, ultimately triggering ferroptosis. Conclusions: These findings reveal that Cr(VI) causes splenic immune injury by disrupting oxidative homeostasis and inducing ferroptosis, providing novel insights for evaluating immunotoxicity and identifying metabolic targets under Cr(VI) pollution. Full article
(This article belongs to the Special Issue Animal Nutritional Metabolism and Toxicosis Disease, 2nd Edition)
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17 pages, 1169 KB  
Review
Bacterial Extracellular Vesicles in the Strategic Interplay Between Pathogens and Hosts
by Jiahui Liang, Mi Li, Jingjing Xu and Shengxia Chen
Microorganisms 2026, 14(6), 1362; https://doi.org/10.3390/microorganisms14061362 - 18 Jun 2026
Viewed by 227
Abstract
Bacterial extracellular vesicles (BEVs) are nanoscale spherical lipid bilayer structures secreted by bacteria, including outer membrane vesicles (OMVs) released by Gram-negative bacteria and membrane vesicles (MVs) produced by Gram-positive bacteria. Although the biogenesis of BEVs requires substantial energy expenditure, these vesicles provide bacteria [...] Read more.
Bacterial extracellular vesicles (BEVs) are nanoscale spherical lipid bilayer structures secreted by bacteria, including outer membrane vesicles (OMVs) released by Gram-negative bacteria and membrane vesicles (MVs) produced by Gram-positive bacteria. Although the biogenesis of BEVs requires substantial energy expenditure, these vesicles provide bacteria with strategic advantages in the evolutionary interplay between pathogens and hosts. BEVs contribute to bacterial adaptation to environmental stress by remodeling membrane components, eliminating toxic substances, promoting biofilm formation, and mediating the interbacterial transfer of antibiotic resistance determinants. They can also function as decoys to protect bacteria from bacteriophage or antibiotic attack, deliver virulence factors, modulate host immune responses to facilitate bacterial colonization, and mediate interspecies competition. This review summarizes the central roles of BEVs as bacterial mediators of environmental responses, with particular emphasis on their involvement in immune regulation, environmental adaptation, and interspecies competition, thereby providing new insights into pathogen evolutionary strategies. Full article
(This article belongs to the Collection Feature Papers in Medical Microbiology)
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10 pages, 2498 KB  
Article
Benincaside A Induces p53-Dependent Transactivation and Fas/CD95-Mediated Apoptosis in HCT 116 Human Colorectal Cancer Cells
by Jai-Sing Yang, Kun-Ching Cheng, Yu-Hsiu Chuang, Ping-Chung Kuo and Tian-Shung Wu
Curr. Issues Mol. Biol. 2026, 48(6), 635; https://doi.org/10.3390/cimb48060635 - 18 Jun 2026
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Abstract
An undescribed seco-kaurane diterpenoid, benincaside A (BA), was isolated from the seeds of Benincasa hispida. The seeds of B. hispida have been traditionally used in folk medicine and previous studies have reported anti-tumor potential in B. hispida seed extracts. Accordingly, we investigated [...] Read more.
An undescribed seco-kaurane diterpenoid, benincaside A (BA), was isolated from the seeds of Benincasa hispida. The seeds of B. hispida have been traditionally used in folk medicine and previous studies have reported anti-tumor potential in B. hispida seed extracts. Accordingly, we investigated the cytotoxicity and underlying mechanisms of BA in colorectal cancer cells. BA inhibited growth in HT29, Colo205, HCT116, and CT26 colorectal cancer cells, as determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, while showing no toxicity toward normal human umbilical vein endothelial cells (HUVEC) and human fibroblast WS-1 cells. In HCT116 cells, BA-induced deoxyribonucleic acid (DNA) damage and apoptosis, as evidenced by morphological changes, 4,6-diamidino-2-phenylindole dihydrochloride (DAPI) staining, and assays of caspase-8 and caspase-3 activities. BA triggered apoptotic cell death via the extrinsic pathway, as indicated by elevated caspase-8 and caspase-3 activities. Intracellular reactive oxygen species (ROS) generation was observed in BA-treated HCT116 cells. The growth-inhibitory effects were significantly attenuated by pretreatment with N-acetylcysteine (NAC, an antioxidant), caffeine (an ATM kinase inhibitor), z-VAD-fmk (pan-caspase inhibitor), or z-IETD-fmk (caspase-8-specific inhibitor). Colorimetric assays confirmed increased caspase-8 and caspase-3 activities in BA-treated cells. This study is the first to report ROS-dependent signaling as a key mechanism underlying BA-induced cell death in HCT116 human colorectal cancer cells. Full article
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