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15 pages, 1073 KB  
Review
The L-A dsRNA Virus and Its Satellites: Totiviruses and Killers in Saccharomyces cerevisiae
by Reed B. Wickner and Herman K. Edskes
Viruses 2026, 18(8), 920; https://doi.org/10.3390/v18080920 - 21 Aug 2026
Viewed by 182
Abstract
A secreted protein toxin encoded by a satellite dsRNA-enabled dissection of the genetic control of replication and expression of a single-segment dsRNA virus, the first Totivirus, L-A. Among the then-novel findings were i. “head-full replication”, ii. a supposedly forbidden “T = 2” capsid [...] Read more.
A secreted protein toxin encoded by a satellite dsRNA-enabled dissection of the genetic control of replication and expression of a single-segment dsRNA virus, the first Totivirus, L-A. Among the then-novel findings were i. “head-full replication”, ii. a supposedly forbidden “T = 2” capsid symmetry based on an asymmetric dimer, iii. a host N-acetyltransferase whose modification of the coat protein is necessary for packaging, iv. Kex1 and Kex2 pro-toxin peptidases leading to discovery of the pre-pro-insulin processing enzymes, and v. specific viral (+) strand sites/structures needed for RNA packaging and (-) strand synthesis. L-A viral (+) strands made in the particle are extruded to the cytoplasm. Those destined for translation are 5′ 7meGMP-capped by a coat protein activity that steals the cap from cellular mRNAs. (+) strands destined for encapsidation in new coats are not capped. Three host-encoded anti-viral systems were found, one based on blocking translation of the viral non-polyA mRNAs (Ski2,3,8 complex), another a 5′->3′ exoribonuclease specific for uncapped molecules (such as the viral (+) strands)(Ski1/Xrn1), and the third a mitochondrial nuclease released in cells undergoing meiosis/sporulation (Nuc1). All of these systems protect cells from virus-induced pathology and have clear animal homologs. The 3′ polyA of yeast mRNAs is dispensable for translation in ski2Δ slh1Δ cells, and such cells are healthy unless the L-A and M dsRNAs are present, suggesting that this polyA is primarily a device allowing cells to distinguish viral and cellular mRNAs. We suggest that the ribosome-associated Ski2,3,8 proteins block 60S subunit joining on polyA mRNAs. Recent evidence of roles for other cellular components controlling viral expression and replication suggests that yeast viruses will continue to be a fertile area for study of viral pathogenesis and host anti-viral systems. Full article
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22 pages, 3791 KB  
Article
Efficacy of Toxfin in Mitigating Mycotoxin Effects in Laying Hens
by Adiel Vieira de Lima, José de Arimatéia de Freitas Pinto, Carlos Henrique do Nascimento, Aline Beatriz Rodrigues, Paloma Eduarda Lopes de Souza, Humberto de Araújo Brito Filho, Raiane dos Santos Silva, Luayne Morais Correa, Ricardo Romão Guerra, Edijanio Galdino da Silva, Apolônio Gomes Ribeiro, Juliana Cristina Ramos Rezende Arrais, Matheus Carlos Romeiro Miranda, Julia Pinto Piccoli and Fernando Guilherme Perazzo Costa
Animals 2026, 16(16), 2613; https://doi.org/10.3390/ani16162613 - 20 Aug 2026
Viewed by 119
Abstract
This study evaluated the effects of supplementation with Toxfin™ Dry, a mineral adsorbent composed of bentonite and sepiolite, on productive performance, egg quality, intestinal morphometry, serum biochemical parameters, antioxidant status, and sphingolipid metabolism of laying hens challenged with T-2 toxin and fumonisin. A [...] Read more.
This study evaluated the effects of supplementation with Toxfin™ Dry, a mineral adsorbent composed of bentonite and sepiolite, on productive performance, egg quality, intestinal morphometry, serum biochemical parameters, antioxidant status, and sphingolipid metabolism of laying hens challenged with T-2 toxin and fumonisin. A total of 480 Hy-Line W-36 laying hens at 25 weeks of age were distributed in a completely randomized design with six treatments and eight replicates of 10 birds each, over 112 days divided into four 28-day cycles. Treatments consisted of a control diet, either uncontaminated or contaminated with 2 mg/kg T-2 toxin and 60 mg/kg fumonisin B1, with or without 1 kg/ton Toxfin™ Dry. Mycotoxin challenge reduced egg production (p < 0.0001), egg weight (p < 0.0001), egg mass (p < 0.0001), feed intake (p < 0.0001), eggshell strength (p < 0.0001) and thickness (p < 0.0001), Haugh unit (p < 0.0001), and villus ratio (p < 0.0001), while increasing inflammatory and hepatic biomarkers, malondialdehyde levels, and the sphinganine ratio, with more pronounced effects under combined contamination. Supplementation with Toxfin™ Dry mitigated most adverse effects, with responses approaching those of the control group. The adsorbent reduces intestinal mycotoxin bioavailability and helps maintain performance and physiological homeostasis in laying hens. Full article
(This article belongs to the Section Animal Nutrition)
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21 pages, 12263 KB  
Article
Can Bacillus thuringiensis Toxin and Sticky Traps Be Used in Integrated Control of Trialeurodes vaporariorum in Greenhouses?
by Guan-Bing Liu, Bo-Wen Liang and Tao Wang
Plants 2026, 15(16), 2511; https://doi.org/10.3390/plants15162511 - 20 Aug 2026
Viewed by 174
Abstract
The greenhouse whitefly (Trialeurodes vaporariorum) causes substantial yield losses and reduced market value of produce in protected agricultural systems worldwide. This study examined the biocontrol potential of recombinant Bacillus thuringiensis (Bt) toxin proteins harboring the LBW08 gene. Within a decision-support system [...] Read more.
The greenhouse whitefly (Trialeurodes vaporariorum) causes substantial yield losses and reduced market value of produce in protected agricultural systems worldwide. This study examined the biocontrol potential of recombinant Bacillus thuringiensis (Bt) toxin proteins harboring the LBW08 gene. Within a decision-support system (DSS) framework, we evaluated the effects of different competent cell lines on toxin expression profiles and assessed the insecticidal performance of two Bt toxin variants (08 and 08bt), both individually and in combination with yellow sticky traps. Our goal was to generate quantitative parameters on population suppression dynamics and cost-effectiveness, providing a basis for DSS-driven pest management recommendations. The 08Bt toxin expressed in JM110 competent cells exhibited superior purity and consistent insecticidal activity against T. vaporariorum nymphs. Notably, the integrated application of 08Bt and yellow sticky traps achieved the highest level of population suppression among all treatments, highest numerical level of population suppression among all treatments, although pairwise differences were not statistically significant, suggesting strong potential for synergistic control. In contrast, no synergistic interaction was observed with the 08 variant. However, the 08 variant combined with traps did not show a comparable numerical improvement. These findings support the development of cost-effective, environmentally sound tactics that can be incorporated into broader IPM strategies for protected agriculture. Full article
(This article belongs to the Special Issue Bio-Control of Plant Pathogens and Pests)
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26 pages, 12863 KB  
Article
Exploring the Molecular Mechanism of Cinnamaldehyde Intervening in Ochratoxin A-Induced Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease Comorbidity: An Integrated Approach Based on Network Pharmacology, Network Toxicology and Molecular Docking
by Mingli Shen, Qingping Shi, Shuang Gao, Beiyan Chen and Jieru Han
Pharmaceuticals 2026, 19(8), 1283; https://doi.org/10.3390/ph19081283 - 13 Aug 2026
Viewed by 231
Abstract
Background/Objective: Cinnamaldehyde (CA) is a naturally occurring bioactive compound derived from the leaves, bark, roots, and flowers of the Chinese medicinal plant Cinnamomum cassia. It exhibits a broad spectrum of pharmacological properties, encompassing antioxidant, antibacterial, anti-diabetic, antifungal, and anticancer activities. Notably, it [...] Read more.
Background/Objective: Cinnamaldehyde (CA) is a naturally occurring bioactive compound derived from the leaves, bark, roots, and flowers of the Chinese medicinal plant Cinnamomum cassia. It exhibits a broad spectrum of pharmacological properties, encompassing antioxidant, antibacterial, anti-diabetic, antifungal, and anticancer activities. Notably, it has shown potential therapeutic benefits in the management of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). Ochratoxin A (OTA), a common contaminant found in foods such as cereals, coffee, and raisins, is also present in traditional Chinese medicinal materials, including Astragalus and liquorice. T2DM and NAFLD share intertwined pathophysiological pathways, including insulin resistance, dyslipidaemia, chronic low-grade inflammation and oxidative stress, with insulin resistance serving as the common pathological hub for both conditions. Consequently, they frequently co-occur and exacerbate each other. OTA exerts dual-targeted toxicity to the pancreas and liver, which may synergistically drive the development of the comorbidity of T2DM and NAFLD. These two processes are mutually causal and together constitute the pathological basis of metabolic comorbidity. Methods: Network toxicology employs toxicological data, gene expression, and protein–protein interaction (PPI) networks to predict the targets of toxins, while network pharmacology, based on systems biology principles, reveals how drugs exert regulatory effects through multiple targets and pathways. In this study, we employed an integrated network toxicology and network pharmacology approach to jointly decipher the potential mechanisms by which CA intervenes in OTA-induced comorbid T2DM-NAFLD. First, a network toxicology approach was employed to preliminarily screen for core toxicological targets responsible for OTA’s pathogenicity. Subsequently, network pharmacology was used to identify potential targets of CA-mediated intervention in the disease. Finally, the common overlap among the CA intervention targets, OTA toxicity targets, and disease targets was defined as the final set of potential targets for CA-mediated intervention in OTA-induced T2DM-NAFLD comorbidity. A PPI network was constructed using the STRING database, and topological analysis was performed with Cytoscape. Core targets were selected using the median values of six parameters—betweenness centrality, closeness centrality, degree centrality, eigenvector centrality, LAC (local average connectivity) score, and network centrality—as cut-off thresholds, and the top 10 key genes were further identified using the cytoHubba plugin. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted via the DAVID database, and the results were visualized on the CNSknowall platform. Lastly, molecular docking of the core targets was performed using the CB-DOCK2 platform to validate binding affinity. Results: Based on an integrated analysis of network toxicology, network pharmacology, and molecular docking, 10 key targets were systematically identified. These may serve as potential mediators of cinnamaldehyde in the treatment of OTA-induced T2DM-NAFLD comorbidity. Among these, six targets—albumin (ALB), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), interleukin-6 (IL-6), tumor necrosis factor (TNF), actin beta (ACTB), and estrogen receptor 1 (ESR1)—possess crystal structures amenable to molecular docking. KEGG enrichment analysis revealed that CA and OTA jointly participate in key pathological processes such as the cancer pathway, the lipid and atherosclerosis pathway, the advanced glycation end-products–receptor for advanced glycation end-products (AGE-RAGE) signaling pathway, the phosphatidylinositol 3-kinase–protein kinase B (PI3K-Akt) signaling pathway, the TNF signaling pathway, and the interleukin-17 (IL-17) signaling pathway. OTA exacerbates inflammatory responses, impairs insulin signaling, promotes hepatic steatosis, and disrupts systemic metabolic homeostasis, ultimately contributing to T2DM-NAFLD comorbidity. Conversely, cinnamaldehyde counteracts these pathological processes through multiple mechanisms, including antioxidant and anti-inflammatory effects as well as regulation of glucose and lipid metabolism, thereby restoring metabolic homeostasis. Conclusions: This study has preliminarily identified the toxicological targets of OTA and the potential intervention targets of CA, offering new avenues for preventing and intervening in OTA-induced metabolic toxicity. Furthermore, it provides a theoretical basis for CA as a potential multi-target therapeutic agent and presents novel insights worthy of further investigation into the prevention of T2DM-NAFLD comorbidity. Full article
(This article belongs to the Special Issue Network Pharmacology of Natural Products, 3rd Edition)
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27 pages, 12811 KB  
Article
Immunoinformatics-Guided Computational Design and In Silico Validation of Multi-Epitope Vaccine Candidates Targeting Canine and Feline Parvoviruses
by Nithyadevi Duraisamy, Abid Ullah Shah, Mohd Yasir Khan, Mohammed Cherkaoui and Maged Gomaa Hemida
Microorganisms 2026, 14(8), 1721; https://doi.org/10.3390/microorganisms14081721 - 5 Aug 2026
Viewed by 325
Abstract
Parvovirus infection causes severe diseases in both feline and canine species. It primarily affects adult cats and dogs but poses a higher risk to kittens and puppies. This virus is highly contagious and is easily transmitted through contaminated food, shared shelter environments, as [...] Read more.
Parvovirus infection causes severe diseases in both feline and canine species. It primarily affects adult cats and dogs but poses a higher risk to kittens and puppies. This virus is highly contagious and is easily transmitted through contaminated food, shared shelter environments, as well as the hands and clothing of people. The recovered species may continue to shed parvovirus in their feces for an extended period, leading to severe environmental contamination. There is no universal vaccine available that protects dogs and cats against parvovirus infections. The main goal of this study is to design a pan-parvovirus multiepitope-based vaccine that could be administered to dogs and cats. We utilized AI-machine learning-incorporated server tools such as IEDB and NetMHCpan to predict B-cell and T-cell epitopes. VaxiJen and ToxinPred were used to analyze immune characteristic features and docking with feline alleles using the HADDOCK server. Following this, the immune response and stability of the vaccine construct were confirmed with disulfide engineering, normal mode analysis, and molecular docking performed with toll-like receptors of both feline and canine (TLR4 and TLR5), and molecular dynamics simulation was performed for 10 ns. The triggered immune response was determined with immuno-simulation (ImmSim), and their activity in a biological environment was reinforced with in silico cloning. The B-cell epitopes (NS1-9, NS2-4, VP1-12 and VP2-9) predicted with the IEDB database were subjected to antigenicity prediction. MHC class I and IFN prediction and MHC class II and IL-4 prediction were performed with IEDB and NetMHCpan. The T-cell epitopes showed high binding affinities with the feline alleles. The final vaccine was designed by combining the top-ranked B-cell epitopes and T-cell epitopes, filtered for high antigenicity, non-allergic, non-toxic, and good solubility, and with the better binding affinity score of the structural and non-structural proteins (NS1, NS2, VP1, and VP2) of feline and canine parvoviruses through linkers and adjuvants. The disulfide bond prediction and normal mode analysis showed that our vaccine construct is stable and flexible. The molecular docking analysis was performed between the designed vaccine epitopes and the TLRs (TLR4–feline and TLR5–canine) with Biovia Discovery Studio using Zdock; it showed better binding interactions with a value of 22.26 (Zdock score), −47.409 (Zrank score) for feline and 16.54 (Zdock score), −134.295 (Zrank score) for canine. A pan-multi-epitope-based vaccine based on the two structural and non-structural proteins (NS1, NS2, VP1, and VP2) was designed and constructed to provide dual protection against parvovirus in both feline and canine species. The molecular docking and molecular dynamics simulation analysis showed higher binding affinities and stable conformations with canine (TLR5) and feline (TLR4) toll-like receptors. Although computational analysis supports the prediction of top-ranked epitopes and their immunogenic properties with greater precision, further experimental validation is required before they can be used against these viruses. Full article
(This article belongs to the Special Issue Viral Infection and Antiviral Drug Development)
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16 pages, 1228 KB  
Article
Mycotoxin Occurrence and Microbiological Quality of Maize Silage Supplemented with Insect Meals for Potential Use in Waterfowl Nutrition
by Matúš Džima, Miroslava Kačániová, Daniel Bíro, Milan Šimko, Branislav Gálik, Michal Rolinec, Ondrej Hanušovský and Miroslav Juráček
Animals 2026, 16(15), 2386; https://doi.org/10.3390/ani16152386 - 3 Aug 2026
Viewed by 284
Abstract
Whole crop maize silage may represent a complementary feed material in waterfowl nutrition, but its hygienic quality and mycotoxin profile remain important safety considerations. This study evaluated the microbiological quality, occurrence, and concentrations of selected mycotoxins in non-inoculated whole crop maize silage under [...] Read more.
Whole crop maize silage may represent a complementary feed material in waterfowl nutrition, but its hygienic quality and mycotoxin profile remain important safety considerations. This study evaluated the microbiological quality, occurrence, and concentrations of selected mycotoxins in non-inoculated whole crop maize silage under five treatments: untreated control (CON), urea-supplemented silage (UR), silage supplemented with full fat Hermetia illucens meal (HI), silage supplemented with full fat Tenebrio molitor meal (TM), and lauric acid-supplemented silage (LA). All the variants were prepared from freshly harvested chopped maize forage and ensiled for 8 weeks in three independent replicates per treatment. The silages were analyzed for microbiological indicators and for the occurrence of fumonisin B1 (FB1), fumonisin B2 (FB2), total aflatoxins (ΣAFs), ochratoxin A (OTA), zearalenone (ZEA), T2 toxin (T2), HT2 toxin (HT2) and deoxynivalenol (DON). The initial occurrence of the selected mycotoxins in the raw materials was also assessed. In the silages, FB1 and FB2 were detected only in CON and UR, whereas both the fumonisins remained below the limit of detection in HI, TM and LA. DON was detected in all the treatments; HI, TM and CON did not differ significantly and showed the highest concentrations, whereas LA and UR were significantly lower and also differed from each other, with the lowest concentration observed in UR. HT2 was detected in CON and in one TM sample, while T2, ΣAFs, OTA and ZEA remained below the limit of detection in all the silage treatments. No significant differences were observed among the treatments in total viable count, lactic acid bacteria, coliform bacteria or microscopic filamentous fungi, and all the monitored microbiological indicators remained at low levels. Overall, the tested additives did not produce a uniform reduction across the monitored mycotoxin profile. A lower fumonisin occurrence was observed in HI, TM and LA, which should be interpreted with caution given the limited replication, whereas DON remained present in all the treatments. Full article
(This article belongs to the Special Issue Optimizing Alternative Protein Sources for Sustainable Poultry Diet)
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22 pages, 23882 KB  
Article
Recombinant BaMtx Preserves the Biological Properties of a Lys49 Phospholipase A2 from Bothrops atrox and Reveals Differential Responses in Tumor and Non-Tumor Cell Models
by Daniel Torrejón, Angie Regalado, Alex Proleón, Víctor Otárola, Fanny Lazo, Edith Rodríguez, Erasmo Colona-Vallejos, Libertad Alzamora-Gonzales, Jherson Cisneros-Gutierrez, Jacquelyne Zarria-Romero, Miryam Paola Alvarez Flores, Renata Nascimento Gomes, Thatiana Corrêa de Melo, Ronnie G. Gavilan, Javier Cárdenas Tenorio, Félix A. Urra, Dan E. Vivas-Ruiz and Armando Yarlequé
Toxins 2026, 18(8), 338; https://doi.org/10.3390/toxins18080338 - 2 Aug 2026
Viewed by 1060
Abstract
Lys49 phospholipase A2 (Lys49-PLA2) homologues are catalytically inactive snake venom toxins with diverse biological activities, but their functional characterization requires recombinant production strategies to overcome the limitations inherent to native venom-derived proteins. Here, we produced recombinant BaMtx (rBaMtx), a Lys49-PLA2 [...] Read more.
Lys49 phospholipase A2 (Lys49-PLA2) homologues are catalytically inactive snake venom toxins with diverse biological activities, but their functional characterization requires recombinant production strategies to overcome the limitations inherent to native venom-derived proteins. Here, we produced recombinant BaMtx (rBaMtx), a Lys49-PLA2 homologue from Bothrops atrox, in the Pichia pastoris KM71 expression system and evaluated whether its biochemical and biological properties were preserved. rBaMtx was secreted into the culture medium, purified by cation-exchange chromatography, and characterized by SDS-PAGE, Western blotting, RP-HPLC (85.9% purity), and MALDI-TOF mass spectrometry, confirming a molecular mass of 13,821 Da. Despite lacking PLA2 activity, rBaMtx retained pronounced myotoxicity in vivo, inducing dose-dependent plasma creatine kinase release and skeletal muscle damage comparable to or greater than native BaMtx. In vitro, rBaMtx reduced viability of murine 4T1 breast carcinoma cells (IC50 = 60.94 µg/mL), altered cell morphology, modestly increased IL-1β release, and produced context-dependent effects in paired human tumor and non-tumor cell models, differing from native BaMtx and crude venom. These findings establish rBaMtx as a reproducible model for investigating the mechanisms and biomedical potential of catalytically inactive Lys49-PLA2 homologues. Full article
(This article belongs to the Special Issue Biochemistry, Pathology and Applications of Venoms)
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22 pages, 12850 KB  
Article
Lineage-Associated Genomic and Phenotypic Features of Bovine Mastitis-Associated Staphylococcus aureus from Northwestern China
by Ting Zhou, Xinying Tao, Zhiying Xue, Yongwang Huang, Yueqi Dong, Mohan Liu, Yilun Hu, Xin Wang and Yan Cui
Microorganisms 2026, 14(8), 1698; https://doi.org/10.3390/microorganisms14081698 - 2 Aug 2026
Viewed by 334
Abstract
Staphylococcus aureus is a major contagious pathogen causing bovine mastitis, with persistence and antimicrobial resistance posing ongoing challenges in dairy herds. From July 2022 to July 2023, 942 mastitis milk samples (267 clinical, 675 subclinical) from 10 farms in northwestern China yielded 98 [...] Read more.
Staphylococcus aureus is a major contagious pathogen causing bovine mastitis, with persistence and antimicrobial resistance posing ongoing challenges in dairy herds. From July 2022 to July 2023, 942 mastitis milk samples (267 clinical, 675 subclinical) from 10 farms in northwestern China yielded 98 S. aureus isolates (10.4%), which were characterized by whole-genome sequencing, antimicrobial susceptibility testing, biofilm assays, and virulence profiling. Ten sequence types, seven clonal complexes, and 16 spa types were identified, dominated by ST1 (42.9%) and ST97 (24.5%). ST1 was mainly associated with subclinical mastitis, whereas ST97 was enriched in clinical cases; a novel ST9955 (13.3%) was exclusively detected in subclinical isolates. No methicillin-resistant S. aureus was detected. Resistance was most frequently observed to penicillin (42.9%), erythromycin (28.6%), clindamycin (22.4%), and tetracycline (10.2%), with higher rates in clinical isolates. 65.3% of isolates exhibited strong biofilm-forming ability, which was significantly more frequent in subclinical cases (70.3% vs. 55.9%, p < 0.05). Virulence genes showed conserved adhesion/biofilm determinants but lineage-dependent distribution of immune evasion and toxin genes, with stable co-occurrence among capsule, biofilm, T7SS, iron acquisition, and immune evasion loci. Overall, the population was diverse but strongly lineage-structured, dominated by a few successful clones, highlighting the value of lineage-resolved surveillance for understanding and controlling bovine mastitis. Full article
(This article belongs to the Section Veterinary Microbiology)
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21 pages, 16090 KB  
Article
Comparative Mitogenomics of Meiacanthus Blennies Reveals Venom System Evolution and Adaptive Traits
by Tengda Luo, Haiyan Yu, Weilin Xiao, Boqiong Wu, Zixuan Liu, Yuqing Tang, Qiang Lin and Yanhong Zhang
Animals 2026, 16(15), 2315; https://doi.org/10.3390/ani16152315 - 27 Jul 2026
Viewed by 391
Abstract
Meiacanthus is a genus of nemophine blennies with an oral venom system, which includes buccal venom glands and canine fangs, and its evolutionary origin remains poorly understood. Here, we sequenced complete mitochondrial genomes of Meiacanthus species and their closely related non-venomous species, and [...] Read more.
Meiacanthus is a genus of nemophine blennies with an oral venom system, which includes buccal venom glands and canine fangs, and its evolutionary origin remains poorly understood. Here, we sequenced complete mitochondrial genomes of Meiacanthus species and their closely related non-venomous species, and performed comparative genomic and phylogenetic analyses to explore Meiacanthus’ evolution. Phylogenetic reconstruction identified Meiacanthus as sister to the (Aspidontus + Petroscirtes) clade, and suggested a probable three-step evolutionary sequence for its oral venom system. Codon usage bias analysis revealed that both natural selection and nucleotide mutations influence nemophine codon usage, shaping a bias that likely plays a crucial role in translational efficiency and regulating mitochondrial gene function. We also identified a unique nemophine tRNA-Cys (GCA) with a degraded DHU loop, which is prompted to be associated with a corresponding shift in codon usage preference. Additionally, all mitochondrial protein-coding genes of Meiacanthus except Cytb exhibited positive selection, with ND4 and ND5 having positively selected sites, likely linked to elevated energy demands for toxin synthesis. Our findings provide the first mitogenomic evidence illuminating the evolutionary pathway of the oral venom system in Meiacanthus, offering crucial insights into the evolution of oral venom systems in non-tetrapod vertebrates. Full article
(This article belongs to the Special Issue Population Genetics of Aquatic Animals)
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11 pages, 2156 KB  
Article
Novel Integrative Mobilizable Elements (IMEs) in Vibrio Chromosomes Linked to Translucent Post-Larvae Disease (TPD)
by Ruyi Hao, Yan Fang, Yang Yang and Mingshu Yang
Fishes 2026, 11(8), 441; https://doi.org/10.3390/fishes11080441 - 27 Jul 2026
Viewed by 296
Abstract
Translucent post-larvae disease (TPD), caused by specific Vibrio parahaemolyticus strains, poses a global threat to shrimp aquaculture. A key virulence factor in these strains is the vhv gene cluster, which encodes toxins central to TPD pathogenesis. While plasmid-borne vhv genes have been extensively [...] Read more.
Translucent post-larvae disease (TPD), caused by specific Vibrio parahaemolyticus strains, poses a global threat to shrimp aquaculture. A key virulence factor in these strains is the vhv gene cluster, which encodes toxins central to TPD pathogenesis. While plasmid-borne vhv genes have been extensively studied, the chromosome-borne vhv genes in TPD-associated strains remain poorly characterized. In this study, we systematically analyzed integrative mobilizable elements (IMEs) on the small secondary chromosomes of TPD-associated V. parahaemolyticus. Seven nearly identical novel IMEs harboring full-length vhv clusters were identified from seven independent strains. These IMEs encode a tyrosine recombinase for site-specific chromosomal integration, yet lack core conjugative transfer machineries including origin-of-transfer (oriT), relaxase, type IV coupling protein (T4CP), and IV secretion system (T4SS), consistent with the definition of non-autonomous IMEs. Each IME carries diverse functional cargo genes, covering five virulence factors (including previously unreported colonization and chemotaxis genes specific to TPD mobile elements), one pollutant-degrading enzyme, and two distinct anti-phage defense systems (PsyrTA and Lamassu-Fam), thereby potentially boosting the host’s fitness and pathogenicity in aquaculture environments. This study provides evidence for the critical role of IMEs in mediating the horizontal transfer of chromosomal vhv, offering new insights into TPD epidemiology and a foundation for developing targeted strategies to mitigate the disease’s impact on shrimp aquaculture. Full article
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17 pages, 4493 KB  
Review
Staphylococcus Aureus Toxins and Asthma: Pathophysiological Mechanisms, Clinical Relevance, and Therapeutic Implications in the Biologics Era
by Diego Bagnasco, Benedetta Bondi, Greta Losacco, Carola Montagnino, Francesca Froio, Elena Tedesco, Gloria D’Alessandro, Ilaria Baglivo, Laura Bruno, Sara Chiappori, Maria José Murillo Jaramillo, Marcello Mincarini, Fulvio Braido and Cristiano Caruso
Toxins 2026, 18(8), 319; https://doi.org/10.3390/toxins18080319 - 23 Jul 2026
Viewed by 677
Abstract
Staphylococcus aureus frequently colonizes the skin and upper airways and produces a broad repertoire of immunomodulatory molecules. In asthma, the most consistent evidence concerns staphylococcal enterotoxins (SEs), which can act both as superantigens and as allergens, and IgE sensitization to SEs (SE-sIgE). SE-sIgE [...] Read more.
Staphylococcus aureus frequently colonizes the skin and upper airways and produces a broad repertoire of immunomodulatory molecules. In asthma, the most consistent evidence concerns staphylococcal enterotoxins (SEs), which can act both as superantigens and as allergens, and IgE sensitization to SEs (SE-sIgE). SE-sIgE is associated with severe asthma, type 2 inflammation, chronic rhinosinusitis with nasal polyps (CRSwNP), exacerbations, and, in some longitudinal studies, persistent airflow obstruction. However, this relationship is not necessarily causal: SE-sIgE may reflect exposure, an immune response, or a biologically active endotype, whereas colonization, local toxin production, and systemic sensitization are not equivalent. SEs simultaneously bind class II MHC molecules and Vbeta regions of the T-cell receptor, activating large fractions of T lymphocytes; they also promote IL-4, IL-5, and IL-13 production, polyclonal B-cell activation, local IgE synthesis, mast-cell degranulation, eosinophilia, and IL-8/neutrophil circuits. Alpha-toxin (Hla) and SEB can damage the epithelial barrier, facilitating allergen penetration and alarmin signalling. These observations support an interaction model in which dysbiosis, barrier dysfunction, and type 2 immunity mutually reinforce one another along the nasobronchial axis. Corticosteroids and antibiotics may modify selected nodes in this circuit, but current evidence is insufficient to recommend decolonization or antitoxin therapy in stable asthma. Biologics interrupt downstream pathways potentially fuelled by toxins: omalizumab neutralizes free IgE; mepolizumab and benralizumab reduce the eosinophilic axis; dupilumab blocks IL-4/IL-13 signalling; and tezepelumab acts upstream on TSLP. Nevertheless, randomized trials stratified by SE-sIgE are lacking, and no evidence demonstrates that these treatments eliminate colonization or toxin production. SE-sIgE therefore appears to be a promising biomarker, particularly in severe asthma with CRSwNP, but it is not yet an autonomous criterion for biologic selection. A broader barrier-organ analysis also identifies nasal, cutaneous, and intestinal colonization as distinct ecological states; atopic dermatitis as a complementary model of toxin-amplified type 2 inflammation; and biofilms and extracellular vesicles as candidate mechanisms of persistent toxin delivery. These data increase biological plausibility but remain indirect for asthma. Full article
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20 pages, 710 KB  
Systematic Review
Hemoadsorptionin Critically Ill Pediatric Oncology and Hemato-Oncology Patients: A Systematic Review with Structured Narrative Synthesis
by Diana Akhmetsharip and Vitaliy Sazonov
Children 2026, 13(7), 961; https://doi.org/10.3390/children13070961 - 21 Jul 2026
Viewed by 502
Abstract
Background: Critically ill children with cancer are vulnerable to sepsis and septic shock, secondary hemophagocytic lymphohistiocytosis (HLH), cytokine release syndrome, delayed chemotherapy clearance, and multiorgan dysfunction. Although hemoadsorption can remove inflammatory mediators and selected toxins, evidence in pediatric oncology remains limited and [...] Read more.
Background: Critically ill children with cancer are vulnerable to sepsis and septic shock, secondary hemophagocytic lymphohistiocytosis (HLH), cytokine release syndrome, delayed chemotherapy clearance, and multiorgan dysfunction. Although hemoadsorption can remove inflammatory mediators and selected toxins, evidence in pediatric oncology remains limited and heterogeneous. Objective: To systematically review the indications, technical application, biomarker and physiologic findings, safety reporting, and clinical outcomes of hemoadsorption in critically ill pediatric oncology and hemato-oncology patients. Methods: We conducted a PRISMA-guided systematic review of PubMed, Scopus, and Web of Science from January 2017 to 1 June 2026, supplemented by reference screening. The search strategy was expanded to capture cartridge-based hemoadsorption and related extracorporeal blood purification modalities, including albumin dialysis systems, but direct synthesis was restricted to cartridge-based hemoadsorption. Evidence was stratified as direct pediatric oncology evidence, supportive hemato-oncology/transplant evidence, or contextual mixed pediatric critical-care evidence. Because included reports were small, uncontrolled, and clinically heterogeneous, synthesis followed a structured narrative approach without meta-analysis. Results: Twelve reports met the inclusion criteria; most were case reports, case series or retrospective observational studies. Hemoadsorption was most often described for septic shock, sepsis-like hyperinflammation, or secondary HLH, with smaller experience in delayed methotrexate clearance, CAR-T-cell-associated cytokine release syndrome, and post-transplant hyperbilirubinemia. Reported devices included CytoSorb, Jafron HA330, and HA230. Direct pediatric oncology reports described before–after reductions in IL-6, IL-10, C-reactive protein, procalcitonin, or ferritin, together with changes in oxygenation, vasoactive support, or organ dysfunction scores. However, all findings were vulnerable to confounding by concurrent antimicrobials, immunomodulation, kidney replacement therapy, source control, and natural recovery. Mortality outcomes were reported using non-equivalent horizons and were summarized narratively. Conclusions: Hemoadsorption has been attempted as adjunctive rescue support in selected critically ill pediatric oncology and hemato-oncology patients. Current evidence is insufficient to determine treatment effect, survival benefit, optimal timing, device selection, anticoagulation strategy, or pharmacokinetic safety. Full article
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14 pages, 4376 KB  
Review
The Potential Target Value of ADP-Ribosylation Factor 6 in Insulin Secretion Regulation and the Treatment of Metabolic Disorders
by Yangyang Wang
Metabolites 2026, 16(7), 508; https://doi.org/10.3390/metabo16070508 - 21 Jul 2026
Viewed by 434
Abstract
Obesity and type 2 diabetes mellitus (T2DM) represent pandemic metabolic illnesses hallmarked by defective pancreatic β-cell function and blunted insulin release. As a conserved small GTPase (guanosine triphosphatase), ADP-ribosylation factor 6 (ARF6) governs fundamental cellular events encompassing vesicle trafficking, cytoskeleton remodeling and lipid [...] Read more.
Obesity and type 2 diabetes mellitus (T2DM) represent pandemic metabolic illnesses hallmarked by defective pancreatic β-cell function and blunted insulin release. As a conserved small GTPase (guanosine triphosphatase), ADP-ribosylation factor 6 (ARF6) governs fundamental cellular events encompassing vesicle trafficking, cytoskeleton remodeling and lipid metabolic turnover. Emerging data confirm that ARF6 acts as a master rheostat of glucose-stimulated insulin secretion (GSIS) in β-cells through downstream cell division control protein 42/Ras-related C3 botulinum toxin substrate 1 (Cdc42/Rac1) cascades. Pathogenic ARF6 hyperactivation triggers a cascade of β-cell lesions: mitochondrial impairment, autophagic suppression and exacerbated inflammatory signaling, accelerating the progression of obesity and T2DM. First-line therapeutics ranging from GLP-1 (Glucagon-like peptide-1) receptor agonists and metformin to SGLT2 (Sodium-Glucose Cotransporter 2) inhibitors partially restore metabolic homeostasis by rectifying aberrant ARF6-dependent signaling axes. This review comprehensively delineates ARF6’s canonical cellular roles, mechanistic bridges connecting ARF6 to β-cell failure and metabolic deterioration, and functional crosstalk between ARF6 and established anti-metabolic pharmacotherapies. We further address unresolved research gaps and prospective translational avenues, offering actionable perspectives to advance ARF6 as a tractable therapeutic target for obesity and T2DM management. Full article
(This article belongs to the Special Issue Management of Diabetes and Its Metabolic Complications)
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22 pages, 2334 KB  
Article
Weather-Related Variations of Mycotoxins in Maize: A 2024 Study from AP Vojvodina (Serbia) and the Republic of Srpska (Bosnia and Herzegovina)
by Elizabet Janić Hajnal, Milan Vukić, Ivana Bogić, Lato Pezo, Milorad Miljić and Ivica Đalović
Foods 2026, 15(14), 2508; https://doi.org/10.3390/foods15142508 - 15 Jul 2026
Viewed by 371
Abstract
Climate variability strongly affects fungal ecology and mycotoxin contamination patterns in maize. This study evaluated the influence of weather conditions during the 2024 growing season on the occurrence and co-occurrence of regulated and emerging mycotoxins in maize from two Southeast European regions: the [...] Read more.
Climate variability strongly affects fungal ecology and mycotoxin contamination patterns in maize. This study evaluated the influence of weather conditions during the 2024 growing season on the occurrence and co-occurrence of regulated and emerging mycotoxins in maize from two Southeast European regions: the Autonomous Province of Vojvodina (APV), Serbia, and the Republic of Srpska (RoS), Bosnia and Herzegovina (BIH). A total of 266 maize samples were analysed using an LC-MS/MS method targeting 21 fungal metabolites. The exceptionally hot and dry summer conditions, particularly the severe drought recorded in APV during August, were associated with regional differences in mycotoxin profiles. APV maize showed higher contamination with drought-related mycotoxins, especially aflatoxins, while fumonisins were highly prevalent in both regions. Overall, fumonisins were the dominant regulated mycotoxins (88.0%), followed by aflatoxins (41.4%) and T-2/HT-2 toxins (31.6%), whereas deoxynivalenol and zearalenone occurred less frequently. Emerging metabolites showed high prevalence, particularly alternariol monomethyl ether (86.5%), moniliformin (74.4%), and ergot alkaloids (53.4%). Co-occurrence analysis revealed 189 different combinations, with up to ten mycotoxins detected simultaneously. These findings demonstrate region-specific weather-driven shifts in maize contamination and emphasize the need for multi-mycotoxin monitoring strategies including both regulated and emerging contaminants. Full article
(This article belongs to the Special Issue Advances in Food Toxin Analysis and Risk Assessment)
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14 pages, 741 KB  
Article
Masseter Muscle Morphometric Changes After Botulinum Toxin Type A Injection: A Prospective 3-Month Study
by Matteo Val, Ludovica Zucchini, Matteo Pollis, Luca Guarda-Nardini, Luca Lombardo, Daniele Manfredini and Anna Colonna
Toxins 2026, 18(7), 306; https://doi.org/10.3390/toxins18070306 - 15 Jul 2026
Viewed by 841
Abstract
Myofascial pain of the masticatory muscles, frequently associated with bruxism, is a prevalent condition with substantial impact on quality of life. Botulinum toxin type A (BoNT-A) is used as an adjunctive treatment for refractory cases, but the temporal pattern of masseter morphometric change [...] Read more.
Myofascial pain of the masticatory muscles, frequently associated with bruxism, is a prevalent condition with substantial impact on quality of life. Botulinum toxin type A (BoNT-A) is used as an adjunctive treatment for refractory cases, but the temporal pattern of masseter morphometric change after injection remained incompletely characterised. This prospective observational pilot study was designed and reported strictly as a 3D imaging and morphometric methodology study; clinical pain and patient-reported outcomes were outside its scope and were not assessed. Eleven adults with myofascial pain and bruxism received BoNT-A (100 U total: 30 U per masseter side, 20 U per anterior temporalis side). Structured-light 3D facial scans (EinScan H, Shining 3D) were acquired at baseline (T0), one month (T1), and three months (T2). A standardised masseter region of interest (“TGL area”) was defined using cutaneous landmarks (tragus, gonion, labial commissure). Measurement precision was confirmed by intra-session repeatability (0.083 ± 0.020 mm), registration accuracy (RMS error 0.189–0.200 mm), and excellent landmark reliability (mean ICC [3, 1] = 0.955, 95% CI: 0.843–0.991). Repeated-measures ANOVA showed a significant effect of time on bilateral surface displacement (F(1.85,18.52) = 14.39, p < 0.001, η2G = 0.44), with significant reductions at T1 (–0.716 ± 0.480 mm; p = 0.002, Hedges’ g = 2.03) and T2 (–0.847 ± 0.588 mm; p = 0.002, g = 1.96) relative to baseline, and no significant change between T1 and T2 (p = 1.000). Changes were bilaterally symmetric (symmetry index at T1: 0.231 ± 0.154 mm). These findings indicate that 3D structured-light scanning reliably detects subtle facial contour changes after BoNT-A injection and may complement clinical and patient-reported assessments; the pilot design and small sample preclude definitive conclusions. Full article
(This article belongs to the Special Issue Efficacy of Botulinum Toxin in Orofacial Pain)
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