Search Results (1,617)

Ischemia–reperfusion (I/R) injury is a complex pathological process underlying numerous acute organ failures and is a significant cause of morbidity and mortality in diseases such as myocardial infarction, stroke, thrombosis, and organ transplantation. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have demonstrated considerable therapeutic potential, but their broad tropism and general repair signaling may limit their efficacy. This review addresses the emerging paradigm of using organ-specific EVs for the treatment of I/R injury in the respective organs. We summarize the existing studies performed on experimental animals showing that these native EVs could possess tissue tropism and carry a specialized cargo of proteins, miRNAs, and lipids tailored to the unique regenerative needs of their organ of origin, enabling them to precisely modulate key processes, including inflammation, apoptosis, oxidative stress, and angiogenesis. However, their clinical translation faces challenges related to scalable production, standardization, and the dualistic nature of their effects, which can be either protective or detrimental, depending on the cellular source and pathophysiological context. Future developments need to focus on overcoming these obstacles through rigorous isolation protocols, engineering strategies such as cargo enrichment and hybrid vesicle creation, and validation in large-animal models. Overall, organ-specific EVs offer a novel, cell-free therapeutic strategy with the potential to significantly improve outcomes in I/R injury. Full article

Spinal cord injury (SCI) often results in long-term locomotor impairments, and strategies to enhance functional recovery remain limited. While epidural electrical stimulation (EES) has shown clinical promise, our understanding of the mechanisms by which it improves function remains incomplete. Here, we use genetic tools in an animal model to perform neuromodulation and treadmill rehabilitation in a manner similar to EES, but with the benefit of the genetic tools and animal model allowing for targeted manipulation, precise quantification of the cells and circuits that were manipulated, and the gathering of extensive kinematic data. We used a viral construct that selectively transduces large diameter afferent fibers (LDAFs) with a designer receptor exclusively activated by a designer drug (hM3Dq DREADD; a chemogenetic construct) to increase the excitability of large fibers specifically, in the rat contusion SCI model. As changes in locomotion with afferent stimulation can be subtle, we carried out a detailed characterization of the kinematics of locomotor recovery over time. Adult Long-Evans rats received contusion injuries and direct intraganglionic injections containing AAV2-hSyn-hM3Dq-mCherry, a viral vector that has been shown to preferentially transduce LDAFs, or a control with tracer only (AAV2-hSyn-mCherry). These neurons then had their activity increased by application of the designer drug Clozapine-N-oxide (CNO), inducing tonic excitation during treadmill training in the recovery phase. Kinematic data were collected during treadmill locomotion across a range of speeds over nine weeks post-injury. Data were analyzed using a mixed effects model chosen from amongst several models using information criteria. That model included fixed effects for treatment (DREADDs vs. control injection), time (weeks post injury), and speed, with random intercepts for rat and time point nested within rat. Significant effects of treatment and treatment interactions were found in many parameters, with a sometimes complicated dependence on speed. Generally, DREADDs activation resulted in shorter stance duration, but less reduction in swing duration with speed, yielding lower duty factors. Interestingly, our finding of shorter stance durations with DREADDs activation mimics a past study in the hemi-section injury model, but other changes, including the variability of anterior superior iliac spine (ASIS) height, showed an opposite trend. These may reflect differences in injury severity and laterality (i.e., in the hemi-section injury the contralateral limb is expected to be largely functional). Furthermore, as with that study, withdrawal of DREADDs activation in week seven did not cause significant changes in kinematics, suggesting that activation may have dwindling effects at this later stage. This study highlights the utility of high-resolution kinematics for detecting subtle changes during recovery, and will enable the refinement of neuromechanical models that predict how locomotion changes with afferent neuromodulation, injury, and recovery, suggesting new directions for treatment of SCI. Full article

This narrative review synthesizes PubMed- and Scopus-indexed studies from 2020 to 2025, including preclinical animal models, prospective cohort studies, and level I and II randomized trials, to compare two leading biologic augmentation strategies: platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC). The review examines underlying mechanisms of action, delivery techniques, imaging biomarkers of graft maturation, patient-reported and functional outcomes, safety profiles, cost-effectiveness, and regulatory frameworks. PRP provides early anti-inflammatory and proangiogenic signaling, while BMAC delivers a concentrated population of mesenchymal stem cells and growth factors to the tendon–bone interface. Both modalities consistently enhance MRI-defined graft maturation, yet evidence of long-term functional or biomechanical superiority remains inconclusive. Emerging therapies such as peptide hydrogels, adipose-derived stem cells, and exosome delivery offer promising avenues for future research. Standardized protocols and large multicenter trials are needed to clarify comparative efficacy and inform personalized rehabilitation strategies. Full article

Background: Tumor-associated macrophages (TAMs) are important contributors to tumor progression and metastasis. Therefore, the identification of molecules that mediate these cells’ tumor-promoting functions is highly warranted. VSIG4 has been proposed as a macrophage immune checkpoint. Hence, we aim to investigate this marker in preclinical models. Methods: Publicly available scRNAseq datasets of human colorectal (CRC) and triple-negative breast (TNBC) carcinomas and their murine counterparts were reanalyzed to investigate the expression of VSIG4 in the different TAM populations. Moreover, tumors were grown in Vsig4-deficient mice to evaluate the effect on primary tumor characteristics. Finally, since liver Kupffer cells and large peritoneal macrophages are at least partly VSIG4-high, and are implicated in metastasis to those organs, the dissemination of CRC cancer cells to those sites was assessed in the Vsig4-deficient mice. Results: We demonstrate that VSIG4 expression in human CRC and TNBC is mostly restricted to TAMs, and that its expression correlates with a worse prognosis. However, a striking finding was that no Vsig4 mRNA nor protein could be detected in the microenvironment of primary CRC and TNBC murine tumors, resulting in a similar tumor growth in wild type versus Vsig4-deficient mice. Moreover, no major differences were observed in metastatic tumor load in the liver and peritoneal cavity, apart from a reduced metastasis to the omentum in Vsig4-deficient animals. Conclusions: Murine cancer models are not suitable to investigate the role of VSIG4 in primary tumors and VSIG4 deficiency did not alter liver nor peritoneal cavity metastasis in murine models, with the exception of the omentum. Full article

In this study, we propose an architectural model for path optimization in cluster order picking within warehouse robotics, utilizing a hybrid approach that combines symbolic control and metaheuristic techniques. Among the optimization strategies, we incorporate bio-inspired metaheuristic algorithms such as the Walrus Optimization Algorithm (WOA), Puma Optimization Algorithm (POA), and Flying Foxes Algorithm (FFA), which are grounded in behavioral models observed in nature. We consider large-scale warehouse robotic systems, partitioned into clusters. To manage shared resources between clusters, the set of clusters is first formulated as a symbolic control design task within a discrete synthesis framework. Subsequently, the desired control goals are integrated into the model, encoded using parallel synchronous dataflow languages; the resulting controller, derived using our safety-focused and optimization-based synthesis approach, serves as the manager for the cluster. Safety objectives address the rigid system behaviors, while optimization objectives focus on minimizing the traveled path of the warehouse robots through the constructed cost function. The metaheuristic algorithms contribute at this stage, drawing inspiration from real-world animal behaviors, such as walruses’ cooperative movement and foraging, pumas’ territorial hunting strategies, and flying foxes’ echolocation-based navigation. These nature-inspired processes allow for effective solution space exploration and contribute to improving the quality of cluster-level path optimization. Our hybrid approach, integrating symbolic control and metaheuristic techniques, demonstrates significantly higher performance advantage over existing solutions, with experimental data verifying the practical effectiveness of our approach. Our proposed algorithm achieves up to 3.01% shorter intra-cluster paths compared to the metaheuristic algorithms, with an average improvement of 1.2%. For the entire warehouse, it provides up to 2.05% shorter paths on average, and even in the worst case, outperforms competing metaheuristic methods by 0.28%, demonstrating its consistent effectiveness in path optimization. Full article

Background: Necrotizing enterocolitis (NEC) is a life-threatening condition characterized by necrosis of the gastrointestinal tract caused by hypoperfusion and hypoxia-induced inflammation. Surgical treatment often requires resection, with high morbidity and mortality. Intestinal tissue engineering using absorbable biomaterials represents a potential alternative. Small intestinal submucosa (SIS) is a biodegradable extracellular matrix (ECM) scaffold that may facilitate regeneration of the native tissue. Objectives: The aim of our study is to investigate the regenerative potential of SIS in a rat model with multiple gastrointestinal defects. Methods: In rats, after a midline laparotomy, an approximately 1 cm full-thickness incision was performed on the anterior gastric wall, on the antimesenteric side of the small and large intestine, each covered with an SIS patch. After three weeks, the graft sites and adjacent fragments were harvested and fixed in 10% neutral buffered formalin. Cross-sections of the grafted area were processed and stained with hematoxylin and eosin for histologic analysis. Results: Among the fifteen Wistar rats used in the study, the survival rate was 80% (12/15). Macroscopic examination of the abdominal cavity after the second surgery showed no complications. Adhesions were present in 92% (11/12). Histological examination demonstrated complete mucosal coverage in all stomach samples, nine of the small intestine, and ten of the large intestine. Mild fibrosis with minimal inflammatory infiltrates predominated. Ulceration with granulation tissue replacement was observed in three small intestine samples. Foreign body reactions were restricted to suture sites. Conclusions: In this multifocal injury model, SIS integrated effectively and supported early regenerative healing across gastric, small-intestinal, and colonic sites at 3 weeks. These data support further studies with longer follow-up, quantitative histology and functional assessment, and evaluation in neonatal-relevant large animal models to determine translational potential for NEC surgery. Full article

Large Language Models (LLMs) encounter significant challenges when applied in specialized domains that require precise and localized information. This problem is particularly critical in regulatory sectors, such as the animal health sector in Brazil, where professionals depend on complex and constantly updated legal norms to perform their work. The generic knowledge encapsulated in traditional LLMs is often insufficient to provide reliable support in these contexts, which can lead to inaccurate or outdated responses. To address this gap, this work presents a practical implementation of a Retrieval-Augmented Generation (RAG) system. We detail the integration of this system with the Plataforma de Defesa Sanitária Animal do Rio Grande do Sul (PDSA-RS), a real platform used for animal production certification. Our solution connects an LLM to an external knowledge base containing specific Brazilian legislation, allowing the model to retrieve relevant legal texts in real time to generate its responses. The principal objective is to demonstrate how this approach can produce accurate and contextually grounded answers for professionals in the veterinary field, assisting in decision-making processes for sanitary certification. Full article

The intestinal mucus layer is a dynamic protective barrier that maintains gut homeostasis, supports immune defense, and regulates host–microbiota interactions. Rodent models have yielded valuable insights, but their intestinal structure and physiology differ from those of humans and pigs. By contrast, the omnivorous pig shares closer anatomical and immunological features with humans, making it a relevant large-animal model in translational studies. In this study, we established a histological workflow for porcine intestine by combining Carnoy’s fixation with Alcian Blue–Periodic Acid–Schiff and Mucicarmine staining. This enabled accurate visualization and quantification of goblet-cell density and mucus thickness across intestinal segments, with a particular focus on Peyer’s patches—key sites of immune surveillance. Both stains produced consistent results. We observed a clear proximal-to-distal gradient, from jejunum to colon, in mucus thickness: the colon displayed the thickest layer (~100 μm), whereas the follicle-associated epithelium over Peyer’s patches in the jejunum and ileum showed a markedly thinner layer (<12 μm) and fewer goblet cells. Immunofluorescence further revealed strong cytokeratin-18 expression in goblet cells, delineating their morphology and polarity. These findings demonstrate region-specific differences in mucus architecture and goblet-cell distribution that likely reflect specialized immune functions, advancing our understanding of the intestinal barrier and informing future strategies to support gut health and immunity. Full article

Background/Objectives: Idiopathic intracranial hypertension (IIH) often features dural venous sinus stenosis; venous sinus stenting (VSS) improves venous outflow and intracranial pressure, but most stents are off-label, and few are engineered for intracranial venous anatomy. The aim was to synthesize animal models relevant to IIH/VSS, catalogue stents used clinically for VSS and summarize corresponding animal data, appraise current preclinical VSS research, and propose a pragmatic preclinical evaluation framework. Methods: We performed a targeted search (PubMed, Web of Science, Scopus; through to May 2025), dual-screened the records in Nested Knowledge, and extracted the model/device characteristics and outcomes as per the predefined criteria. Results: We identified 65 clinical VSS studies; most were retrospective and used off-label carotid/peripheral/biliary stents (Precise, Zilver, and Wallstent were the most frequent). Recent dedicated systems (River, BosStent) have limited animal evidence; VIVA has GLP porcine venous peripheral data demonstrating its patency, structural integrity, and benign healing outcomes. Rodent models reproduce obesity/androgen drivers with modest, sustained ICP elevation; large animal models show the technical feasibility of in sinus implantation, but no chronic focal venous stenosis model fully mirrors the IIH condition. Conclusions: Despite broad clinical uptake, the translational underpinnings of VSS in IIH remain incomplete: most devices lack intracranial venous-specific preclinical validation, and there is no existing animal model that recapitulates both IIH biology and focal sinus stenosis. Full article

Long COVID (LC), also known as post-acute sequelae of COVID-19 infection (PASC), is a heterogeneous and debilitating chronic disease that currently affects 10 to 20 million people in the U.S. and over 420 million people globally. With no approved treatments, the long-term global health and economic impact of chronic LC remains high and growing. LC affects children, adolescents, and healthy adults and is characterized by over 200 diverse symptoms that persist for months to years after the acute COVID-19 infection is resolved. These symptoms target twelve major organ systems, causing dyspnea, vascular damage, cognitive impairments (“brain fog”), physical and mental fatigue, anxiety, and depression. This heterogeneity of LC symptoms, along with the lack of specific biomarkers and diagnostic tests, presents a significant challenge to the development of LC treatments. While several biological abnormalities have emerged as potential drivers of LC, a causative factor in a large subset of patients with LC, involves reservoirs of virus and/or viral RNA (vRNA) that persist months to years in multiple organs driving chronic inflammation, respiratory, muscular, cognitive, and cardiovascular damages, and provide continuous viral antigenic stimuli that overstimulate and exhaust CD4⁺ and CD8⁺ T cells. In this review, we (i) shed light on persisting virus and vRNA reservoirs detected, either directly (from biopsy, blood, stool, and autopsy samples) or indirectly through virus-specific B and T cell responses, in patients with LC and their association with the chronic symptomatology of LC; (ii) explore potential mechanisms of inflammation, immune evasion, and immune overstimulation in LC; (iii) review animal models of virus reservoirs in LC; (iv) discuss potential T cell immunotherapeutic strategies to reduce or eliminate persistent virus reservoirs, which would mitigate chronic inflammation and alleviate symptom severity in patients with LC. Full article

The current agent-based evolutionary models for animal communication rely on simplified signal representations that differ significantly from natural vocalizations. We propose a novel agent-based evolutionary model based on text-to-audio (TTA) models to generate realistic animal vocalizations, advancing from VAE-based real-valued genotypes to TTA-based textual genotypes that generate bird songs using a fine-tuned Stable Audio Open 1.0 model. In our sexual selection framework, males vocalize songs encoded by their genotypes while females probabilistically select mates based on the similarity between males’ songs and their preference patterns, with mutations and crossovers applied to textual genotypes using a large language model (Gemma-3). As a proof of concept, we compared TTA-based and VAE-based sexual selection models for the Blue-and-white Flycatcher (Cyanoptila cyanomelana)’s songs and preferences. While the VAE-based model produces population clustering but constrains the evolution to a narrow region near the latent space’s origin where reconstructed songs remain clear, the TTA-based model enhances the genotypic and phenotypic diversity, drives song diversification, and fosters the creation of novel bird songs. Generated songs were validated by a virtual expert using the BirdNET classifier, confirming their acoustic realism through classification into related taxa. These findings highlight the potential of combining large language models and TTA models in agent-based evolutionary models for animal communication. Full article

Artificial Intelligence (AI) is widely recognized as a force that will fundamentally transform traditional chicken farming models. It can reduce labor costs while ensuring welfare and at the same time increase output and quality. However, the breadth of AI’s contribution to chicken farming has not been systematically quantified on a large scale; few people know how far current AI has actually progressed or how it will improve chicken farming to enhance the sector’s sustainability. Therefore, taking “AI + sustainable chicken farming” as the theme, this study retrieved 254 research papers for a comprehensive descriptive analysis from the Web of Science (May 2003 to March 2025) and analyzed AI’s contribution to the sustainable in recent years. Results show that: In the welfare dimension, AI primarily targets disease surveillance, behavior monitoring, stress detection, and health scoring, enabling earlier, less-invasive interventions and more stable, longer productive lifespans. In economic dimension, tools such as automated counting, vision-based weighing, and precision feeding improve labor productivity and feed use while enhancing product quality. In the environmental dimension, AI supports odor prediction, ventilation monitoring, and control strategies that lower emissions and energy use, reducing farms’ environmental footprint. However, large-scale adoption remains constrained by the lack of open and interoperable model and data standards, the compute and reliability burden of continuous multi-sensor monitoring, the gap between AI-based detection and fully automated control, and economic hurdles such as high upfront costs, unclear long-term returns, and limited farmer acceptance, particularly in resource-constrained settings. Environmental applications are also underrepresented because research has been overly vision-centric while audio and IoT sensing receive less attention. Looking ahead, AI development should prioritize solutions that are low cost, robust, animal friendly, and transparent in their benefits so that return on investment is visible in practice, supported by open benchmarks and standards, edge-first deployment, and staged cost–benefit pilots. Technically, integrating video, audio, and environmental sensors into a perception–cognition–action loop and updating policies through online learning can enable full-process adaptive management that improves welfare, enhances resource efficiency, reduces emissions, and increases adoption across diverse production contexts. Full article

Background: Three-dimensional (3-D) printing paired with tissue-engineering strategies promises to overcome the volume, contour, and donor-site limitations of traditional breast reconstruction. Patient-specific, bioabsorbable constructs could enable one-stage procedures that better restore aesthetics and sensation. Methods: A narrative review was conducted following a targeted PubMed search (inception—April 2025) using combinations of “breast reconstruction,” “tissue engineering,” “3-D printing,” and “scaffold.” Pre-clinical and clinical studies describing polymer-based chambers or scaffolds for breast mound or nipple regeneration were eligible. Data was extracted on scaffold composition, animal/human model, follow-up, and volumetric or histological outcomes. Results: Forty-three publications met inclusion criteria: 35 pre-clinical, six early-phase clinical, and two device reports. The predominant strategy (68% of studies) combined a vascularized fat flap with a custom 3-D-printed chamber to guide adipose expansion. Poly-lactic acid, poly-glyceric acid, poly-lactic-co-glycolic acid, poly-4-hydroxybutyrate, polycarbonate, and polycaprolactone were the principal polymers investigated; only poly-4-hydroxybutyrate and poly-lactic acid have been tested for nipple scaffolds. Bioabsorbable devices supported up to 140% volume gain in large-animal models, but even the best human series (≤18 months) achieved sub-mastectomy volumes and reported high seroma rates. Mechanical testing showed elastic moduli (5–80 MPa) compatible with native breast tissue, yet long-term load-bearing data are scarce. Conclusions: Current evidence demonstrates biocompatibility and incremental adipose regeneration, but clinical translation is constrained by small sample sizes, incomplete resorption profiles, and regulatory uncertainty. Standardized large-animal protocols, head-to-head polymer comparisons, and early human feasibility trials with validated outcome measures are essential next steps. Nevertheless, the convergence of 3-D printing and tissue engineering represents a paradigm shift that could ultimately enable bespoke, single-stage breast reconstruction with superior aesthetic and functional outcomes. Full article

Keel bone lesions (KBLs) represent a relevant welfare concern in laying hens, arising from complex interactions among genetics, housing systems, and management practices. This study presents the development of an image analysis system for the automated detection and classification of KBLs in slaughterhouse videos, enabling scalable and retrospective welfare assessment. In addition to lesion classification, the system can track and count individual carcasses, providing estimates of the total number of specimens with and without significant lesions. Videos of brown laying hens from a commercial slaughterhouse in northeastern Italy were recorded on the processing line using a smartphone. Six hundred frames were extracted and annotated by three independent observers using a three-scale scoring system. A dataset was constructed by combining the original frames with crops centered on the keel area. To address class imbalance, samples of class 1 (damaged keel bones) were augmented by a factor of nine, compared to a factor of three for class 0 (no or mild lesion). A YOLO-based model was trained for both detection and classification tasks. The model achieved an F1 score of 0.85 and a mAP@0.5 of 0.892. A BoT-SORT tracker was evaluated against human annotations on a 5 min video, achieving an F1 score of 0.882 for the classification task. Potential improvements include increasing the number and variability of annotated images, refining annotation protocols, and enhancing model performance under varying slaughterhouse lighting and positioning conditions. The model could be applied in routine slaughter inspections to support welfare assessment in large populations of animals. Full article

Background: Engineered nanoparticles (NPs)—titanium dioxide, silver, zinc oxide and silica—are widely used in cosmetics for UV protection, antimicrobial activity and texturising effects. Chronic consumer-level exposure may impair skin-barrier integrity, disturb microbiome composition and dysregulate immune signalling via the gut–skin axis. Current regulatory frameworks typically omit chronic- or microbiome-focused safety assessments, leaving potential gaps. Objectives: This study aimed to evaluate the long-term effects of cosmetic-relevant NPs (titanium dioxide, silver, zinc oxide, silica) on skin and gut microbiota, epithelial-barrier integrity and immune signalling—including telocyte- and exosome-mediated pathways—and to identify regulatory shortcomings, particularly the absence of microbiome endpoints, validated chronic models and consideration of vulnerable populations. Methods: Following PRISMA 2020, PubMed, Scopus and Web of Science were searched for English-language in vivo animal or human studies (December 2014–April 2025) meeting chronic-exposure criteria (≥90 days in rodents or >10% of lifespan in other species; for humans, prolonged, repetitive application over months to years consistent with cosmetic use). Although not registered in PROSPERO, the review adhered to a pre-specified protocol. Two independent reviewers screened studies; risk of bias was assessed using a modified SYRCLE tool (animal) or adapted NIH guidance (zebrafish). Owing to heterogeneity, findings were synthesised narratively. Results: Of 600 records, 450 unique articles were screened, 50 full texts were assessed and 12 studies were included. Oral exposure predominated and was associated with dysbiosis, barrier impairment, immune modulation and metabolic effects. Dermal models showed outcomes from minimal change to pronounced immune activation, contingent on host susceptibility. Comparative human–animal findings are summarised; telocyte and exosome pathways were largely unexplored. Regulatory reviews (EU SCCS, US FDA and selected Asian frameworks) revealed no requirements for chronic microbiome endpoints. Limitations: Evidence is limited by the small number of eligible studies, heterogeneity in NP characteristics and exposure routes, predominance of animal models and a scarcity of longitudinal human data. Conclusions: Cosmetic nanoparticles may disrupt the microbiome, compromise barrier integrity and trigger immune dysregulation—risks amplified in vulnerable users. Existing regulations lack requirements for chronic exposure, microbiome endpoints and testing in vulnerable groups, and neglect mechanistic pathways involving telocytes and exosomes. Long-term, real-world exposure studies integrating gut–skin microbiome and immune outcomes, and harmonised global nanomaterial-safety standards, are needed to ensure safer cosmetic innovation. Full article