Search Results (5,145)

Polyomaviruses establish long-term infection in the kidney and are intermittently shed in urine. However, the relationship between kidney-resident viral genomes and urinary shedding during persistent infection remains poorly defined. Using a genetically barcoded murine polyomavirus library, we tracked thousands of viral lineages in vivo by pairing longitudinal urine sampling with endpoint barcode sequencing of kidney tissue in four mice. Across all animals, kidney infection consistently resolved into two stable viral populations, with near-silent persistence as the dominant fate. Most kidney-resident barcodes were never detected in late urine at late stages of infection, even though many reached substantial abundance within the kidney, demonstrating that kidney viral genome levels alone do not predict urinary shedding. In contrast, only a small minority of kidney barcodes contributed disproportionately to urine virus output at late timepoints, and these barcodes exhibited stable longitudinal behavior, with repeated detection in urine over time and markedly higher peak urine abundance than late non-shed or random barcode controls. Shedding behavior was not explained by input virus stock abundance, barcode sequence features, predicted miRNA targeting, or ongoing reseeding from blood or other tissues. Instead, barcodes that ultimately dominated late urine already showed elevated urine detection early after infection, indicating that shedding fate is established early and maintained throughout persistent infection. Together, these findings reveal that persistent kidney infection is a structured reservoir composed of a large population of deeply restricted viral genomes and a smaller, stable subset that repeatedly produces urine-detectable viruses, with concurrent smoldering infections and latency-like restriction representing one possible model to explain the sharply different probabilities of shedding among kidney-resident genomes. Full article

Rural communities in many low- and middle-income countries (LMICs) remain isolated from reliable access to critical sites and social services due to inadequate transport connectivity. Formal planning approaches to improve rural networked transport infrastructure (RNTI) remain limited, underfunded and deprioritized relative to urban systems. Where resources do exist, they largely emphasize roads, despite the fact that nearly one-third of the global rural population lives more than two kilometers from an all-weather road and relies primarily on walking and intermediate modes of transport (IMTs), such as bicycles, motorcycles, and animal-powered vehicles. This review examines planning approaches for RNTI with a focus on non-car-centric, multimodal mobility. It assesses prioritization frameworks, including multi-criteria analysis, that incorporate social, environmental, accessibility, and economic considerations. Long-term outcomes are strengthened by participatory methods, multimodal planning and cross-sectoral integration that align transport investments with health, education, agriculture, and renewable resource goals. Addressing persistent barriers such as funding constraints, data gaps, and maintenance challenges requires improved spatial mapping and travel-time analysis to better identify mobility needs and guide investment decisions. The limited body of formal literature on the topic of RNTI necessitates the inclusion of grey literature and practitioner sources and underscores the call for additional research. Full article

Errors are an unavoidable part of veterinary practice; however, little is known about how veterinary support staff perceive and deal with errors in their veterinary teams. This study examined perception of errors, contributing factors, and approaches to error management among veterinary support staff in German-speaking countries. A cross-sectional online survey was conducted, including 205 fully completed questionnaires. Reported errors were most often linked to tasks such as billing, team interaction, and handling and restraining animals. The most frequently reported contributing factors were time pressure, high workload, and communication problems. Most respondents reported that errors are openly spoken up about in everyday work (68%) and discussed within the team (76%). At the same time, perceptions of feeling safe to report an error varied: while 69% reported always or mostly feeling safe to speak up, 31% felt safe only sometimes, rarely or never. In addition, 16% of participants reported having deliberately not disclosed an error. According to 81% of respondents, no structured error reporting or management system was in place in their workplace. Overall, the findings show that error handling among veterinary support staff remains largely informal and individual, highlighting an important area for further research, improved reporting structures and training. Full article

Ammonia is one of the most important and widely produced basic chemicals worldwide. However, this highly toxic gas is also produced in livestock farming and a variety of industrial processes, posing a potential threat to humans, animals and the environment and also significantly contributing to the formation of persistent particulate matter. The aim of this project was to develop a textile-based adsorber material and to demonstrate a suitable test system for purifying ammonia-contaminated air from production-related sources using the example of pig fattening and PCB production. This aim was achieved through the wash-resistant immobilization of polyacrylic acid on a polyester needle felt at laboratory, pilot plant and industrial scales. In addition, various system concepts have been developed in which air or phosphoric acid can flow through the adsorber textile, whereby in the latter case, the phosphoric acid is both actively involved in ammonia adsorption and also serves to elute the bound ammonia, enabling continuous and low-maintenance operation. Concurrently, the high-quality inorganic fertilizer ammonium phosphate is produced. In summary, an efficient alternative to existing solutions for ammonia minimization has been developed, which is fundamentally characterized by its universal applicability in different load scenarios, including small mobile systems in production facilities with local ammonia pollution, in addition to scenarios for large-scale agricultural operations. Full article

Dog bite incidents constitute significant public health, animal welfare, and economic concerns with substantial physical and psychological consequences for victims. Despite legislative responses, research indicates that breed-focused interventions are ineffective in reducing dog bite risk. Human behaviour, caregiving practices, and environmental context all play central roles in the expression of human-directed canine aggression. Current methods of assessing dog bite risk remain largely unstructured, dog-centred, and reliant on subjective judgement and provocative behavioural testing. These approaches exhibit limited predictive validity and poor reliability, and are vulnerable to bias, raising serious concerns for public safety, judicial fairness, and animal welfare. Comparable challenges in human violence risk assessment led to the development of an evidence-based structured professional judgement (SPJ) assessment framework, which combines empirical risk factors with individualised case formulation and dynamic risk management. An SPJ framework for dog bite risk would ensure the systematic consideration of empirically supported static and dynamic risk factors relating to the dog, caregivers, and related environmental conditions, while supporting the development of targeted risk reduction strategies. Conclusion: Developing an SPJ approach offers a more scientifically grounded, ethically defensible, and prevention-focused method for managing dog bite risk, with potential benefits for public safety, animal welfare, and professional practice. Full article

Background: Cartilage defects remain a clinical challenge due to the limited intrinsic repair capacity of hyaline cartilage, driving increasing interest in blood-derived products, including platelet-rich plasma (PRP). Variability in PRP preparation and activation protocols limits reproducibility and clinical translation, particularly in large animal models where species-specific differences are an additional cue. This study aimed to standardize and optimize in pigs a protocol for plasma rich in growth factors (PRGF), a leukocyte-poor PRP, aligned with current human clinical practice. Methods: Whole blood from six female pigs was processed via three centrifugation protocols and activated with varying CaCl₂ concentrations to evaluate gelation and morphology. PRGF was characterized through hematological analysis, ELISA-based quantification of soluble factors, and structural imaging of fibrin gel via histology and scanning electron microscopy. Data were further analyzed using protein–protein interaction networks, hierarchical clustering, and comparative human PRGF proteomic profiles. Results: Protocol with 400× g centrifugation followed by 13.3 mM CaCl₂ activation achieved the most favorable performance, yielding the highest platelet recovery, effective leukocyte clearance, and consistent formation of a well-organized fibrin network. Porcine activated PRGF showed substantial overlap in detected factors and concentration ranges with human activated PRGF prepared with the same protocol. Conclusions: These findings establish a robust, clinically aligned porcine PRGF protocol and support the pig as a relevant translational model for PRP-based regenerative strategies, providing a reliable platform for preclinical evaluation of cartilage therapies. Full article

Carotenoids are increasingly studied for their robust antioxidant capacity, anti-inflammatory potential, protective vision and validated contribution to human health. Carotenoids are mainly obtained through chemical synthesis and plant extraction, which results in relatively high costs for producing carotenoids. However, microalgae represent a sustainable and high-yield platform for natural carotenoid production, with advantages including rapid growth, high pigment accumulation, and broad environmental adaptability. This review summarizes recent biotechnological advances in enhancing carotenoid production, with a focus on metabolic engineering, environmental regulation, and cultivation strategies. CRISPR/Cas9 enables precision metabolic pathway engineering, while environmental factors like light, nutrients, and stress significantly influence yield. Different cultivation strategies allow carotenoids to fulfill commercial or research needs. The two-stage strategy achieves rapid biomass increase during the growth stage, then shifts to accumulate carotenoids. This regulatory mode significantly reduces cell death by continuous stress, providing high productivity and stability in large-scale production. Carotenoids participate in many innovative applications across various fields, including treatments in medicine, skin protection in cosmetics, protein stabilization in foods, enhancing animals’ survival and so on. Future research will integrate bioprocess optimization, precision strain engineering, and adaptive environmental strategies to scale high-value microalgal carotenoid production as a commercially and environmentally viable solution. Full article

Three-dimensional (3D) bioprinting provides new options for airway reconstruction by enabling the fabrication of customizable, biodegradable scaffolds designed to support in situ tissue regeneration. Building on our established large-animal platform, in which two cm bioprinted tracheal grafts combined with refined surgical techniques and adjunctive laser intervention have achieved long-term survival exceeding three months, the present study aims to explore long-segment (≥four cm) tracheal transplantation. We evaluated the fabrication feasibility and regeneration patterns of extrusion-based 3D bioprinted polycaprolactone (PCL) tracheal grafts in a porcine model. The grafts were implanted via end-to-end anastomosis with adjunctive mechanical stabilization and followed by serial bronchoscopic surveillance, gross examination, and histological analysis. The two cm PCL tracheal grafts achieved reproducible survival exceeding three months when combined with refined surgical techniques, structured postoperative airway management, and optimized wound coverage. Histological analysis revealed multi-lineage tissue formation—including cartilage, muscle, glands, and epithelium—was observed. Cartilage regeneration followed a staged maturation process, compared to epithelial regeneration, although continuous by 12 weeks, remained developmentally immature. A single long-segment transplantation was explored in a single preliminary case, providing an initial technical observation of feasibility; however, definitive conclusions regarding long-term survival or regeneration cannot be drawn. These findings further characterize regenerative responses in a large-animal model and highlight critical translational barriers—fabrication constraints, airway biomechanics, and delayed epithelial maturation—that require systematic investigation before long-segment tracheal reconstruction can advance toward clinical application. Full article

The French Society for Toxinology (SFET) held its 31st annual meeting (RT31) on 1–2 December 2025 at Hôtel Le Saint Paul in Nice, France, on the famous French Riviera. The meeting, which gathered 75 participants from around the world, was organised there for the second consecutive year, while previous editions were all held in Paris. The RT31 main theme, “Toxins: Playing with and fighting them”, explored recent, cutting-edge research in the field of animal venoms and of toxins from algal, animal, bacterial, fungal, plant and microbial origins, in emphasizing the evolution of the toxins, their modes of action and roles, and ways of counteracting intoxinations. These key topics were largely covered through 26 oral and 18 poster communications, organized into three main thematic areas covering three specific aspects of toxinology, along with a traditional fourth, more general session enabling participants to present recent data outside of these themes but nevertheless providing valuable information to the field. This report presents the abstracts of nine of the invited lectures, 14 of the selected lectures, and 16 of the posters, in accordance with the authors’ agreement to publish them. Also, we announce the winners of the “Best Oral Communication” and “Best Poster Communication” awards, which recognize the outstanding contributions of young researchers and their inventive work in toxinology. Full article

Background: Local delivery after resection of high-grade glioma, particularly glioblastoma (GBM), aims to increase intratumoral drug exposure while limiting systemic toxicity. The only U.S. Food and Drug Administration (FDA)-approved implantable intracranial chemotherapy is the carmustine (1,3-bis[2-chloroethyl]-1-nitrosourea; BCNU)-impregnated polyanhydride wafer (Gliadel wafer), indicated for newly diagnosed high-grade glioma and recurrent GBM. More than two decades of clinical use and randomized data show that intracavitary chemotherapy is feasible and confers a modest survival benefit in carefully selected patients. Nevertheless, Gliadel wafer has not altered the overall poor prognosis of GBM because of biological resistance to nitrosoureas, constrained brain-parenchymal pharmacokinetics, and device-related adverse effects. Objective: The aim is to synthesize clinical and preclinical evidence defining the current limitations of Gliadel wafer and to outline strategies for next-generation local delivery systems, with emphasis on GBM within the broader high-grade glioma setting. Methods: A narrative review of randomized and observational clinical studies, pharmacokinetic studies, and preclinical investigations evaluating Gliadel wafer and potential next-generation local delivery systems in GBM and other high-grade gliomas was performed. Results: The literature delineates key limitations of Gliadel wafer: short diffusion distances and burst-weighted carmustine release, high tumor cell resistance to carmustine due to heterogeneity, and device-related side effects. Emerging approaches to address these limitations include (i) multidrug systems with synergistic effects against GBM cells; (ii) advanced biomaterials that enable controlled and sustained release; and (iii) targeted agents with minimal off-target effects. Testing newer generations of local drug-delivery systems in more predictive translational models, such as patient-derived organoids and spontaneous large-animal glioma models, is essential to maximize the translatability of preclinical studies to human studies. However, broader adoption of spontaneous large-animal glioma models is constrained by ethical oversight, animal-welfare considerations, cost, and limited availability compared with rodent platforms. Conclusions: Next-generation local drug-delivery systems should include multiple synergistic tumor-selective drugs that can be released in a controlled, sustained manner deep into the residual tumor. Preclinical testing of these systems should be conducted in clinically relevant animal models that are more translatable than those used in early Gliadel wafer studies. Full article

Background: Myocardial ischemic injury, encompassing acute myocardial infarction (MI) and ischemia/reperfusion (I/R) injury, remains a major cause of cardiac morbidity and mortality worldwide, and is driven by interconnected molecular and cellular processes, including cardiomyocyte apoptosis, inflammatory activation, mitochondrial dysfunction, oxidative stress, and impaired angiogenesis. Mesenchymal stem cell (MSC)-derived exosomes have emerged as a promising cell-free nanotherapeutic strategy for cardiac repair due to their ability to transfer bioactive molecules that modulate multiple signaling networks involved in myocardial survival and regeneration. This systematic review aimed to synthesize evidence on the mechanistic basis of MSC-derived exosome mediated cardioprotection in myocardial ischemic injury. Methods: A systematic search of Ovid MEDLINE, Scopus, and Web of Science was conducted to identify studies investigating the effects of MSC-derived exosomes on myocardial ischemic injury. Eligible studies included clinical and preclinical models of MI or I/R injury assessing functional, biochemical, and molecular outcomes. Results: Seven preclinical studies published between 2015 and 2025 met the inclusion criteria. Exosome administration consistently improved cardiac function, reduced infarct size, and preserved myocardial architecture. Biochemical analyses revealed decreased cardiac injury markers, alongside suppressed apoptosis, inflammation, and oxidative stress. Mechanistically, MSC-derived exosomes delivered regulatory miRNAs (e.g., miR-19a, miR-125b, miR-205, miR-294) and lncRNAs (HAND2-AS1) that modulated key signaling pathways including PI3K/Akt, JAK2/STAT3, HAND2-AS1/miR-17-5p/Mfn2, and HIF-1α/VEGF. These molecular effects collectively inhibited apoptotic and inflammatory responses, enhanced mitochondrial integrity, and promoted angiogenesis and myocardial repair. Conclusions: MSC-derived exosomes confer robust cardioprotection against myocardial ischemic injury through integrated anti-apoptotic, anti-inflammatory, antioxidant, and pro-angiogenic mechanisms. Their multifaceted bioactivity, low immunogenicity, and potential for targeted delivery highlight their potential as a next-generation nanomedicine for ischemic heart disease. Future studies should emphasize standardized exosome production, mechanistic profiling, and translational validation in large-animal and clinical models. Full article

Dietary fiber (DF) has a profound influence on human health mainly by modulating the gut microbiota. This review provides an overview of DF derived from cereals, legumes, fruits, vegetables, fungi, and seaweeds, specifically addressing the relationship between microbial utilization and source-specific structural characteristics (such as linking patterns, conformation, solubility, and fermentability). Due to these structural properties, different DFs display selective microbial responses that favor fermentation and the production of short-chain fatty acids (SCFAs). These microbial responses and fermentation-derived metabolites associated with DF intake may contribute to reduced risk of obesity, diabetes, inflammatory bowel disease, and other chronic disorders. This review does not address the trial heterogeneity, dose response, safety, and conflicting evidence, and much of the available evidence is largely observational and heterogeneous. Future studies should focus on dose–response trials of defined DF structures with standardized microbiome and metabolomic endpoints, including validation in human interventions. This review summarizes the DF source and structure, selective changes in the microbiota across various study types, including in vitro, animal models, and human studies, and how these relate to overall health. Full article

Coumarin-based compounds are recognized for their chemical versatility and diverse biological activities, yet clinical applications remain largely confined to 4-hydroxycoumarin anticoagulants. To bridge this translational gap, coumarin scaffolds have been increasingly employed in prodrug design to enable controlled activation, targeted delivery, and theranostic functionality. This review critically evaluates whether coumarin-based prodrugs fulfill their therapeutic promise or remain primarily preclinical tools across oncology, inflammation, infectious diseases, and cardiovascular disorders. Strategies including enzymatic-, pH-, redox-, and light-triggered activation, as well as subcellular targeting and multifunctional hybrids, are discussed. Preclinical studies demonstrate improved bioavailability, reduced off-target toxicity, and real-time fluorescence monitoring, yet most compounds remain at the in vitro or small-animal model stage. Despite their mechanistic and conceptual potential, clinical translation is constrained by molecular complexity, pharmacokinetics, safety, and regulatory challenges. Overall, coumarins constitute a versatile multifunctional platform whose therapeutic impact relies on rigorous in vivo validation and strategic optimization. Full article

Three-dimensional (3D) ex vivo imaging of cleared tissue from intact brains from animal models, human brain surgical specimens, and large postmortem human and non-human primate brain specimens is essential for understanding physiological neural connectivity and pathological alterations underlying neurological and neuropsychiatric disorders. Contemporary light-sheet microscopy enables rapid, high-resolution imaging of large, cleared samples but is limited by the orthogonal arrangement of illumination and detection optics, which constrains specimen size. Light-sheet theta microscopy (LSTM) overcomes this limitation by employing two oblique illumination paths while maintaining a perpendicular detection geometry. Here, we report the development of a next-generation, fully integrated and user-friendly LSTM system that enables uniform subcellular-resolution imaging (with subcellular resolution determined by the lateral performance of the system) throughout large specimens without constraining lateral (XY) dimensions. The system provides a seamless workflow encompassing image acquisition, data storage, pre- and post-processing, enhancement and quantitative analysis. Performance is demonstrated by high-resolution 3D imaging of intact mouse brains and human brain samples, including complete downstream analyses such as digital neuron tracing, vascular reconstruction and design-based stereological analysis. This enhanced and accessible LSTM implementation enables rapid quantitative mapping of molecular and cellular features in very large biological specimens. Full article

Despite comprehensive and multi-modal therapy, outcomes for children and adolescents with rhabdomyosarcoma (RMS) have plateaued over the past four decades. This is not for a lack of progress in the basic and translational studies of RMS. Indeed, advances in animal models and/or patient tissue sample acquisition and analysis have improved our understanding of RMS biology. Large-scale sequencing efforts have generated transcriptomic, genomic, and epigenomic datasets that highlight the heterogeneity of RMS and have the potential to improve prognostication and the application of precision medicine in patients with RMS. However, few of these discoveries have been clinically translated, and limitations to the accessibility, uniformity, and application of these new models and datasets hinder their utility. Here, we discuss how advances in understanding RMS biology, optimization of preclinical models, and strategies for translating basic science discoveries to the clinic can potentially improve outcomes for patients with RMS. Full article