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Search Results (649)

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20 pages, 3940 KiB  
Article
24 Hours Ahead Forecasting of the Power Consumption in an Industrial Pig Farm Using Deep Learning
by Boris Evstatiev, Nikolay Valov, Katerina Gabrovska-Evstatieva, Irena Valova, Tsvetelina Kaneva and Nicolay Mihailov
Energies 2025, 18(15), 4055; https://doi.org/10.3390/en18154055 (registering DOI) - 31 Jul 2025
Abstract
Forecasting the energy consumption of different consumers became an important procedure with the creation of the European Electricity Market. This study presents a methodology for 24-hour ahead prediction of the energy consumption, which is suitable for application in animal husbandry facilities, such as [...] Read more.
Forecasting the energy consumption of different consumers became an important procedure with the creation of the European Electricity Market. This study presents a methodology for 24-hour ahead prediction of the energy consumption, which is suitable for application in animal husbandry facilities, such as pig farms. To achieve this, 24 individual models are trained using artificial neural networks that forecast the energy production 1 to 24 h ahead. The selected features include power consumption over the last 72 h, time-based data, average, minimum, and maximum daily temperatures, relative humidities, and wind speeds. The models’ Normalized mean absolute error (NMAE), Normalized root mean square error (NRMSE), and Mean absolute percentage error (MAPE) vary between 16.59% and 19.00%, 22.19% and 24.73%, and 9.49% and 11.49%, respectively. Furthermore, the case studies showed that in most situations, the forecasting error does not exceed 10% with several cases up to 25%. The proposed methodology can be useful for energy managers of animal farm facilities, and help them provide a better prognosis of their energy consumption for the Energy Market. The proposed methodology could be improved by selecting additional features, such as the variation of the controlled meteorological parameters over the last couple of days and the schedule of technological processes. Full article
(This article belongs to the Special Issue Application of AI in Energy Savings and CO2 Reduction)
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14 pages, 2806 KiB  
Article
Pilot Study on Resuscitation Volume’s Effect on Perfusion and Inflammatory Cytokine Expression in Peri-Burn Skin: Implications for Burn Conversion
by Tamer R. Hage, Edward J. Kelly, Eriks Ziedins, Babita Parajuli, Cameron S. D’Orio, David M. Burmeister, Lauren Moffatt, Jeffrey W. Shupp and Bonnie C. Carney
Eur. Burn J. 2025, 6(3), 42; https://doi.org/10.3390/ebj6030042 - 28 Jul 2025
Viewed by 141
Abstract
Fluid resuscitation after thermal injury is paramount to avoid burn shock and restore organ perfusion. Both over- and under-resuscitation can lead to unintended consequences affecting patient outcomes. While many studies have examined systemic effects, limited data exist on how fluid resuscitation impacts burn [...] Read more.
Fluid resuscitation after thermal injury is paramount to avoid burn shock and restore organ perfusion. Both over- and under-resuscitation can lead to unintended consequences affecting patient outcomes. While many studies have examined systemic effects, limited data exist on how fluid resuscitation impacts burn wound progression in the acute period. Furthermore, the mechanisms underlying burn wound progression remain not fully understood. This study used a swine model to investigate how varying resuscitation levels affect peri-burn wound dynamics. Twenty-seven female Yorkshire pigs were anesthetized, subjected to 40% total body surface area burn and 15% hemorrhage, then randomized (n = 9) to receive decision-support-driven (adequate, 2–4 mL/kg/%TBSA), fluid-withholding (under, <1 mL/kg/%TBSA), or high-constant-rate (over, >>4 mL/kg/%TBSA) resuscitation. Pigs were monitored for 24 h in an intensive care setting prior to necropsy. Laser Doppler Imaging (LDI) was conducted pre-burn and at 2, 6, 12, and 24 h post burn to assess perfusion. Biopsies were taken from burn, peri-burn (within 2 cm), and normal skin. RNA was isolated at 24 h for the qRT-PCR analysis of IL-6, CXCL8, and IFN-γ. At hour 2, LDI revealed increased peri-burn perfusion in over-resuscitated animals vs. under-resuscitated animals (p = 0.0499). At hour 24, IL-6 (p = 0.0220) and IFN-γ (p = 0.0253) were elevated in over-resuscitated peri-burn skin. CXCL8 showed no significant change. TUNEL staining revealed increased apoptosis in over- and under-resuscitated peri-burn skin. Differences in perfusion and cytokine expression based on resuscitation strategy suggest that fluid levels may influence burn wound progression. Full article
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20 pages, 3154 KiB  
Article
The Effect of Astaxanthin on Ochratoxin A-Induced Intestinal Injury in Chickens Through RIPK1/RIPK3/MLKL Pathway
by Ruiwen Fan, Wenqi Tian, Bo Jin, Yuhang Sun, Miao Long, Shuhua Yang and Peng Li
Antioxidants 2025, 14(8), 915; https://doi.org/10.3390/antiox14080915 - 25 Jul 2025
Viewed by 302
Abstract
Ochratoxin A (OTA), as a mycotoxin, can contaminate a variety of feeds and foods. Existing studies have shown that the main toxicity of OTA to organisms is nephrotoxicity, but the toxic mechanism to other organs is still worthy of further study. Whether OTA [...] Read more.
Ochratoxin A (OTA), as a mycotoxin, can contaminate a variety of feeds and foods. Existing studies have shown that the main toxicity of OTA to organisms is nephrotoxicity, but the toxic mechanism to other organs is still worthy of further study. Whether OTA causes intestinal damage through the necroptosis pathway mediated by RIPK1/RIPK3/MLKL remains to be elucidated. Astaxanthin (AST), a feed additive with strong antioxidant properties, was used as an antidote to evaluate the alleviation effect on OTA-induced intestinal injury and the underlying mechanism in this research. Chickens are the most sensitive animals to OTA except pigs. Therefore, 70 white-feathered chickens (n = 15) and Chicken Small Intestinal Epithelial Cells (CSIECs) were used as experimental subjects. Experimental models were established by single or combined exposure of OTA (1.0 mg/kg on chickens for 21 d; 2 μM on CSIEC for 24 h) and AST (100 mg/kg on chickens for 21 d; 40 μM on CSIEC for 24 h). In this study, AST significantly ameliorated OTA-induced intestinal damage by restoring the expression of tight junction proteins (Occludin-1, Claudin-1, and ZO-1), attenuating severe histopathological alterations, mitigating the inflammatory response (elevated pro-inflammatory cytokines and reduced anti-inflammatory mediators), and suppressing necroptosis through downregulation of RIPK1, RIPK3 and MLKL expression. Combined evidence from animal experiments and cell culture experiments demonstrated that AST alleviated the necroptosis and inflammation caused by OTA in CSIECs and the intestine of chickens through the RIPK1/RIPK3/MLKL signaling pathway, thereby reducing the damage caused by OTA. Full article
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16 pages, 32599 KiB  
Article
The Connection Between Lipid Metabolism in the Heart and Liver of Wuzhishan Pigs
by Yuwei Ren, Feng Wang, Ruiping Sun, Xinli Zheng, Yanning Lin and Zhe Chao
Biomolecules 2025, 15(7), 1024; https://doi.org/10.3390/biom15071024 - 16 Jul 2025
Viewed by 262
Abstract
Lipid metabolism is critical for the physiological activities of signal transduction, metabolic regulation, and energy provision, and Wuzhishan (WZS) pigs are a promising animal model for studying human diseases. However, lipid metabolites in the heart and liver of WZS pigs are indistinct. In [...] Read more.
Lipid metabolism is critical for the physiological activities of signal transduction, metabolic regulation, and energy provision, and Wuzhishan (WZS) pigs are a promising animal model for studying human diseases. However, lipid metabolites in the heart and liver of WZS pigs are indistinct. In this study, we detected gene expression, blood biochemical parameters, and metabolic profiles of hearts and livers of WZS and Large White (LW) pigs, and analyzed correlations between metabolites. The results showed that the fatty acid metabolic process was present in both the heart and liver, and was more dominant in the liver. Although the expression of lipid absorption-related genes of CYP7A1 increased in the liver, CEBPB levels increased in both the liver and heart; the fatty acid beta-oxidation genes RXRA and ACSS2 also showed increased expression. The quantity of metabolites related to lipid synthesis decreased in the liver, heart, and blood for WZS pigs compared to that of LW pigs, indicating a balance of lipid synthesis and breakdown for WZS pigs. Moreover, the lipid metabolites in the liver and heart exhibited strong correlations with each other and showed similar correlations to blood biochemical parameters, respectively. This study declared the balance of lipid metabolism in both the heart and liver, and identified their connections for WZS pigs. Full article
(This article belongs to the Section Molecular Medicine)
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14 pages, 1519 KiB  
Article
Efficacy of EA575 as an Antitussive and Mucoactive Agent in Preclinical In Vivo Models
by Matthias Hufnagel, André Rademaekers, Anika Weisert, Hanns Häberlein and Sebastian Franken
Biomedicines 2025, 13(7), 1673; https://doi.org/10.3390/biomedicines13071673 - 8 Jul 2025
Viewed by 433
Abstract
Background: The efficacy of EA575 in the treatment of respiratory diseases is described in various clinical studies, improving patients’ disease-related symptoms. However, mechanistic in vivo data proving its beneficial effects are limited. Methods: Focusing on the treatment of acute airway inflammation and accompanying [...] Read more.
Background: The efficacy of EA575 in the treatment of respiratory diseases is described in various clinical studies, improving patients’ disease-related symptoms. However, mechanistic in vivo data proving its beneficial effects are limited. Methods: Focusing on the treatment of acute airway inflammation and accompanying cough, this study aimed to elucidate antitussive and mucoactive properties of EA575, applying two animal models. Animals were treated orally twice daily for 7 days, resulting in 43, 215.2, or 430.5 mg/kg bw/d of EA575. Antitussive effects were investigated within an acute lung inflammation model of bleomycin-treated guinea pigs after citric acid exposure. Hereby, the number of coughs, enhanced pause (penH), and bronchoalveolar lavage fluid (BALF) were investigated. Mucoactivity of EA575 was assessed within a murine model, determining phenol red concentration in BALF. Results: EA575 treatment within the acute lung inflammation model reduced cough events up to 56% while reducing inflammatory cell influx in BALF dose-dependently, e.g., reducing neutrophils in BALF up to 70.9%. This suggests a strong connection between anti-inflammatory and antitussive properties of EA575. Furthermore, penH decreased in a dose-dependent manner, suggesting an ease in respiration. Mucoactivity was shown by a dose-dependent increase in phenol red concentration in BALF up to 38.9%. Notably, EA575/salbutamol co-administration resulted in enhanced phenol red secretion compared to respective single administrations. Conclusions: These data highlight the benefits of EA575 in treating cough-related respiratory diseases, particularly when accompanied by sputum, as EA575 has been shown to obtain mucoactivity. Furthermore, the combinatory effect of EA575/salbutamol treatment provides a foundation for future research in the treatment of chronic respiratory diseases. Full article
(This article belongs to the Section Drug Discovery, Development and Delivery)
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9 pages, 1016 KiB  
Article
TinyML-Based Swine Vocalization Pattern Recognition for Enhancing Animal Welfare in Embedded Systems
by Tung Chiun Wen, Caroline Ferreira Freire, Luana Maria Benicio, Giselle Borges de Moura, Magno do Nascimento Amorim and Késia Oliveira da Silva-Miranda
Inventions 2025, 10(4), 52; https://doi.org/10.3390/inventions10040052 - 4 Jul 2025
Cited by 1 | Viewed by 384
Abstract
The automatic recognition of animal vocalizations is a valuable tool for monitoring pigs’ behavior, health, and welfare. This study investigates the feasibility of implementing a convolutional neural network (CNN) model for classifying pig vocalizations using tiny machine learning (TinyML) on a low-cost, resource-constrained [...] Read more.
The automatic recognition of animal vocalizations is a valuable tool for monitoring pigs’ behavior, health, and welfare. This study investigates the feasibility of implementing a convolutional neural network (CNN) model for classifying pig vocalizations using tiny machine learning (TinyML) on a low-cost, resource-constrained embedded system. The dataset was collected in 2011 at the University of Illinois at Urbana-Champaign on an experimental pig farm. In this experiment, 24 piglets were housed in environmentally controlled rooms and exposed to gradual thermal variations. Vocalizations were recorded using directional microphones, processed to reduce background noise, and categorized into “agonistic” and “social” behaviors using a CNN model developed on the Edge Impulse platform. Despite hardware limitations, the proposed approach achieved an accuracy of over 90%, demonstrating the potential of TinyML for real-time behavioral monitoring. These findings underscore the practical benefits of integrating TinyML into swine production systems, enabling early detection of issues that may impact animal welfare, reducing reliance on manual observations, and enhancing overall herd management. Full article
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20 pages, 1211 KiB  
Article
Unsupervised Anomaly Detection with Continuous-Time Model for Pig Farm Environmental Data
by Heng Zhou, Seyeon Chung, Malik Muhammad Waqar, Muhammad Ibrahim Zain Ul Abideen, Arsalan Ahmad, Muhammad Ans Ilyas, Hyongsuk Kim and Sangcheol Kim
Agriculture 2025, 15(13), 1419; https://doi.org/10.3390/agriculture15131419 - 30 Jun 2025
Viewed by 416
Abstract
Environmental air anomaly detection is crucial for ensuring the healthy growth of livestock in smart pig farming systems. This study focuses on four key environmental variables within pig housing: temperature, relative humidity, carbon dioxide concentration, and ammonia concentration. Based on these variables, it [...] Read more.
Environmental air anomaly detection is crucial for ensuring the healthy growth of livestock in smart pig farming systems. This study focuses on four key environmental variables within pig housing: temperature, relative humidity, carbon dioxide concentration, and ammonia concentration. Based on these variables, it proposes a novel encoder–decoder architecture for anomaly detection based on continuous-time models. The proposed framework consists of two embedding layers: an encoder module built around a continuous-time neural network, and a decoder composed of multilayer perceptrons. The model is trained in a self-supervised manner and optimized using a reconstruction-based loss function. Extensive experiments are conducted on a multivariate multi-sequence dataset collected from real-world pig farming environments. Experimental results show that the proposed architecture significantly outperforms existing transformer-based methods, achieving 92.39% accuracy, 92.08% precision, 85.84% recall, and an F1 score of 88.19%. These findings highlight the practical value of accurate anomaly detection in smart farming systems; timely identification of environmental irregularities enables proactive intervention, reduces animal stress, minimizes disease risk, and ultimately improves the sustainability and productivity of livestock operations. Full article
(This article belongs to the Special Issue Modeling of Livestock Breeding Environment and Animal Behavior)
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19 pages, 3308 KiB  
Article
Transcriptomic Changes in the Frontal Cortex of Juvenile Pigs with Diet-Induced Metabolic Dysfunction-Associated Liver Disease
by Kyle Mahon, Mohammed Abo-Ismail, Emily Auten, Rodrigo Manjarin and Magdalena Maj
Biomedicines 2025, 13(7), 1567; https://doi.org/10.3390/biomedicines13071567 - 26 Jun 2025
Viewed by 542
Abstract
Background/Objectives: Neurodegenerative disorders have a complex multifactorial pathogenesis that develop decades before the initial symptoms occur. One of the crucial factors in the development of neurodegenerative disorders is an unbalanced diet. A pediatric animal model of diet-induced metabolic dysfunction-associated steatotic liver disease [...] Read more.
Background/Objectives: Neurodegenerative disorders have a complex multifactorial pathogenesis that develop decades before the initial symptoms occur. One of the crucial factors in the development of neurodegenerative disorders is an unbalanced diet. A pediatric animal model of diet-induced metabolic dysfunction-associated steatotic liver disease (MASLD) was established by feeding juvenile Iberian pigs a diet high in fat and fructose for 10 weeks. The aim of this study was to investigate the initial molecular imbalances in the frontal cortex (FC) of diet-induced juvenile MASLD pig model and determine whether these changes are associated with neuronal loss. Methods: Eighteen 15-day-old Iberian pigs were randomly assigned to either a standard diet (SD) or a Western diet (WD) for 10 weeks. A short-term recognition memory test and animal activity was recorded during the study. Animals were euthanized in week 10, and the FC and hippocampus (HIP) tissue samples were collected for immunohistochemistry and transcriptomics analyses. Results: WD-fed pigs developed MASLD. There were no significant differences in animals’ activity or recognition memory between WD and SD. To identify and quantify mature neurons, NeuN immunostaining intensity was measured, which was significantly lower in the FC of WD than SD (p ≤ 0.05), but it did not change in HIP (p ≥ 0.05). The Wnt/β-catenin pathway, which promotes neuronal survival and neurogenesis, was downregulated in FC of WD-fed pigs (p ≤ 0.05). Similarly, cytoskeleton organization and extracellular matrix biological processes were downregulated in FC of WD-fed pigs (p ≤ 0.05), whereas the mitochondrial respiratory chain complex and mitochondrion increased in FC of WD compared with SD (p ≤ 0.01). There were several other significantly modulated pathways including signal transduction, cell migration, axon guidance, and calcium ion binding. Conclusions: The high-fructose, high-fat diet led to neuronal loss in the frontal cortex of MASLD pigs and dysregulated gene expression of the Wnt/β-catenin signaling pathway, cytoskeleton organization, extracellular matrix, and mitochondrial respiratory chain—all pathways that are found deregulated in neurodegnerative diseases. Full article
(This article belongs to the Special Issue Cellular and Molecular Biology of Neurodegenerative Disorders)
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18 pages, 4066 KiB  
Article
Furosemide Promotes Inflammatory Activation and Myocardial Fibrosis in Swine with Tachycardia-Induced Heart Failure
by Nisha Plavelil, Robert Goldstein, Michael G. Klein, Luke Michaelson, Mark C. Haigney and Maureen N. Hood
Int. J. Mol. Sci. 2025, 26(13), 6088; https://doi.org/10.3390/ijms26136088 - 25 Jun 2025
Viewed by 264
Abstract
Loop diuretics like furosemide are commonly used in heart failure (HF) treatment, but their effects on disease progression are still unclear. Furosemide treatment accelerates HF deterioration in a swine model, but the mechanism of acceleration is poorly understood. We hypothesized that furosemide activates [...] Read more.
Loop diuretics like furosemide are commonly used in heart failure (HF) treatment, but their effects on disease progression are still unclear. Furosemide treatment accelerates HF deterioration in a swine model, but the mechanism of acceleration is poorly understood. We hypothesized that furosemide activates inflammatory signaling in the failing left ventricular (LV) myocardium, leading to adverse remodeling of the extracellular matrix (ECM). A total of 14 Yorkshire pigs underwent permanent transvenous pacemaker implantation and were paced at 200 beats per minute; 9 non-instrumented pigs provided controls. Seven paced animals received normal saline, and seven received furosemide at a dose of 1 mg/kg intramuscularly. Weekly echocardiograms were performed. Furosemide-treated animals reached the HF endpoint a mean of 3.2 days sooner than saline-treated controls (mean 28.9 ± 3.8 SEM for furosemide and 32.1 ± 2.5 SEM for saline). The inflammatory signaling protein transforming growth factor-beta (TGF-β) and its downstream proteins were significantly (p ≤ 0.05) elevated in the LV after furosemide treatment. The regulatory factors in cell proliferation, mitogen-activated protein kinase signaling pathway proteins, and matrix metalloproteinases were elevated in the furosemide-treated animals (p ≤ 0.05). Our data showed that furosemide treatment increased ECM remodeling and myocardial fibrosis, reflecting increased TGF-β signaling factors, supporting prior results showing worsened HF. Full article
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14 pages, 2327 KiB  
Article
Safety and Efficacy Evaluation of Ultrasound Aspirators in Intramedullary Spinal Cord Tumors Surgery: An Experimental Study on a Swine Model
by Mauro Palmieri, Alessandro Pesce, Mattia Capobianco, Massimo Corsini, Giorgia Iovannitti, Fulvio Aloj, Giuseppa Zancana, Vincenzo Esposito, Maurizio Salvati, Antonio Santoro, Gianpaolo Cantore and Alessandro Frati
Brain Sci. 2025, 15(7), 670; https://doi.org/10.3390/brainsci15070670 - 21 Jun 2025
Viewed by 373
Abstract
Introduction: Intradural extramedullary and intramedullary spinal tumors are rare, complex to treat, and require advanced surgical techniques. Ultrasonic aspirators, commonly used for tumor removal, can cause sensory and motor deficits, including loss of motor evoked potentials (MEPs). This study aims to evaluate [...] Read more.
Introduction: Intradural extramedullary and intramedullary spinal tumors are rare, complex to treat, and require advanced surgical techniques. Ultrasonic aspirators, commonly used for tumor removal, can cause sensory and motor deficits, including loss of motor evoked potentials (MEPs). This study aims to evaluate the safety and efficacy of ultrasonic aspirators in intramedullary tumor surgery using a swine model, comparing different systems and techniques. Methods: Ten pigs underwent D1-D3 laminectomy and myelotomy, with adipose tissue simulating a tumor. The ultrasonic aspirators were tested under varying conditions (fragmentation power, suction, application time, and vibration mode). The primary endpoint is to evaluate the impact of the chosen variables on motor function damage. The secondary endpoints are histological evaluation of the type of damage caused by ultrasound aspirators and the effect of steroid drugs on MEPs’ impairment recovery. Results: Ultrasound aspirators can cause a significant MEP signal reduction when used in continuous mode, with fragmentation power >30 for more than 2 min (p < 0.001). Suction does not affect MEPs. When used in alternating/pulsatile mode, fragmentation power and application time do not affect MEPs. The two-way ANOVA analysis on the interaction between fragmentation power and application time in continuous mode did not demonstrate a significant interaction (p = 0.155). Time alone does not affect motor damage (p = 0.873). Betamethasone can restore MEPs’ signal after damage if administered immediately. Conclusions: Using ultrasonic aspirators in an animal model of intramedullary tumor surgery is safe. The main factor that resulted in the responsibility of motor function impairment is the fragmentation power. Full article
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20 pages, 2627 KiB  
Article
The Originally Established PBE Cell Line as a Reliable In Vitro Model for Investigating SIV Infection and Immunity
by Xi-Chen Bai, Kohtaro Fukuyama, Leonardo Albarracin, Yoshiya Imamura, Fu Namai, Weichen Gong, Wakako Ikeda-Ohtsubo, Keita Nishiyama, Julio Villena and Haruki Kitazawa
Int. J. Mol. Sci. 2025, 26(12), 5764; https://doi.org/10.3390/ijms26125764 - 16 Jun 2025
Viewed by 459
Abstract
Previously, we developed a porcine bronchial epithelial cell line designated as PBE cells and demonstrated that this cell line possesses functional Toll-like receptor 3 (TLR3), triggering the expressions of interferons (IFNs), antiviral factors, and inflammatory cytokines after its stimulation with the synthetic double-stranded [...] Read more.
Previously, we developed a porcine bronchial epithelial cell line designated as PBE cells and demonstrated that this cell line possesses functional Toll-like receptor 3 (TLR3), triggering the expressions of interferons (IFNs), antiviral factors, and inflammatory cytokines after its stimulation with the synthetic double-stranded ARN poly(I:C). In this work, we aimed to further characterize the PBE cell line as a reliable in vitro model for investigating swine influenza virus (SIV) infection and immunity. We evaluated the capacity of two SIV subtypes, H1N1 and H3N2, to replicate and induce cytopathic effects in PBE cells and to modulate the expressions of IFNs, antiviral factors, inflammatory cytokines, and negative regulators of the TLR signaling. We demonstrated that PBE cells are susceptible to both H1N1 and H3N2. SIV infected PBE cells inducing notable cytopathic effects as shown by the alteration of transepithelial electrical resistance (TEER) and cilia. Both SIV subtypes replicated in PBE cells in similar proportion and altered TEER values in comparable magnitudes. However, SIV H3N2 induced higher alterations of cilia than H1N1. SIV infection induced changes in all the immune factors evaluated in PBE cells. We detected quantitative differences when the subtypes H1N1 and H3N2 were compared. The fold expression changes of IFN-β, Mx1, Mx2, IFITM1, OAS1, OAS2, and OASL were higher in PBE cells infected with H3N2 than in cells challenged with H1N1. In addition, although both subtypes stimulated IL-8 expression, only the H3N2 induced IL-6 in infected PBE cells. SIV H1N1 and H3N2 also upregulated the expressions of the negative regulators A20, BCL-3, and MKP-1, while only H1N1 increased SIGIRR and Tollip. Immortalized respiratory cell lines from pigs can be useful in vitro systems for the study of viral infections and immune responses. These studies are of importance in the context of influenza infections not only for the agricultural field because pigs are natural hosts of these viruses but also because these animals serve as intermediate reservoirs of viruses that can threaten humans’ health. We demonstrated here that the PBE cell line can be a useful in vitro model to study SIV infection and immunity. Full article
(This article belongs to the Section Molecular Immunology)
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29 pages, 713 KiB  
Review
The Evolving Landscape of Functional Models of Autism Spectrum Disorder
by Jai Ranjan and Aniket Bhattacharya
Cells 2025, 14(12), 908; https://doi.org/10.3390/cells14120908 - 16 Jun 2025
Viewed by 1042
Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1–3% of the population globally. Owing to its multifactorial origin, complex genetics, and heterogeneity in clinical phenotypes, it is difficult to faithfully model ASD. In essence, ASD is an umbrella term for a group [...] Read more.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1–3% of the population globally. Owing to its multifactorial origin, complex genetics, and heterogeneity in clinical phenotypes, it is difficult to faithfully model ASD. In essence, ASD is an umbrella term for a group of individually rare disorders, each risk gene accounting for <1% of cases, threaded by a set of overlapping behavioral or molecular phenotypes. Validated behavioral tests are considered a gold standard for ASD diagnosis, and several animal models (rodents, pigs, and non-human primates) have traditionally been used to study its molecular basis. These models recapitulate the human phenotype to a varying degree and have been indispensable to preclinical research, but they cannot be used to study human-specific features such as protracted neuronal maturation and cell-intrinsic attributes, posing serious limitations to translatability. Human stem cell-based models, both as monolayer 2D cultures and 3D organoids and assembloids, can circumvent these limitations. Generated from a patient’s own reprogrammed cells, these can be used for testing therapeutic interventions that are more condition and patient relevant, targeting developmental windows where the intervention would be most effective. We discuss some of these advancements by comparing traditional and recent models of ASD. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Autism Spectrum Disorder)
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17 pages, 4187 KiB  
Article
Lactobacillus fermentum ZC529 Protects Intestinal Epithelial Barrier Integrity by Activating the Keap1-Nrf2 Signaling Pathway and Inhibiting the NF-κB Signaling Pathway
by Zian Yuan, Lang Huang, Zhenguo Hu, Junhao Deng, Yehui Duan, Qian Jiang, Bi’e Tan, Xiaokang Ma, Chen Zhang and Xiongzhuo Tang
Antioxidants 2025, 14(6), 732; https://doi.org/10.3390/antiox14060732 - 14 Jun 2025
Viewed by 588
Abstract
The probiotic bacteria Lactobacillus fermentum ZC529 (L.f ZC529) has been identified from the colon of the Diannan small-ear (DSE) pig, but its intestinal protective function still lacks investigation. Here, we established a dextran sodium sulfate (DSS)-induced intestinal oxidative stress model in both [...] Read more.
The probiotic bacteria Lactobacillus fermentum ZC529 (L.f ZC529) has been identified from the colon of the Diannan small-ear (DSE) pig, but its intestinal protective function still lacks investigation. Here, we established a dextran sodium sulfate (DSS)-induced intestinal oxidative stress model in both Drosophila and porcine small intestinal epithelial (IPEC-J2) cell lines to explore the anti-oxidative and anti-inflammatory effects of L.f ZC529. The data showed that the intestinal colonization of L.f ZC529 counteracted DSS-induced intestinal oxidative stress and excessive reactive oxygen species (ROS) generation by activation of the CncC pathway, a homology of the nuclear factor erythroid 2-related factor 2 (Nrf2) in mammalian systems. Moreover, L.f ZC529 supplementation prevented flies from DSS-induced intestinal barrier damage, inflammation, abnormal excretory function, and shortened lifespan. Finally, L.f ZC529 also attenuated DSS-induced intestinal injury in the IPEC-J2 cell line by activating the Keap1-Nrf2 signaling and inhibiting the NF-κB signaling pathways. Together, this study unraveled the profound intestinal protective function of L.f ZC529 and provides its potential application as a new antioxidant in improving animal intestinal health as well as in developing a new probiotic in the food industry. Full article
(This article belongs to the Special Issue Natural Antioxidants in Animal Nutrition)
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19 pages, 3876 KiB  
Article
Improving Ex Vivo Nasal Mucosa Experimental Design for Drug Permeability Assessments: Correcting Mucosal Thickness Interference and Reevaluating Fluorescein Sodium as an Integrity Marker for Chemically Induced Mucosal Injury
by Shengnan Zhao, Jieyu Zuo, Marlon C. Mallillin, Ruikun Tang, Michael R. Doschak, Neal M. Davies and Raimar Löbenberg
Pharmaceuticals 2025, 18(6), 889; https://doi.org/10.3390/ph18060889 - 13 Jun 2025
Viewed by 1149
Abstract
Objectives: Ex vivo nasal mucosa models provide physiologically relevant platforms for evaluating nasal drug permeability; however, their application is often limited by high experimental variability and the absence of standardized methodologies. This study aimed to improve experimental design by addressing two major [...] Read more.
Objectives: Ex vivo nasal mucosa models provide physiologically relevant platforms for evaluating nasal drug permeability; however, their application is often limited by high experimental variability and the absence of standardized methodologies. This study aimed to improve experimental design by addressing two major limitations: the confounding effects of mucosal thickness and the questionable reliability of fluorescein sodium (Flu-Na) as an integrity marker for chemically induced mucosal injury. Methods: Permeability experiments were conducted using porcine nasal tissues mounted in Franz diffusion cells, with melatonin and Flu-Na as model compounds. Tissues of varying thickness were collected from both intra- and inter-individual sources, and a numerical simulation-based method was employed to normalize apparent permeability coefficients (Papp) to a standardized mucosal thickness of 0.80 mm. The effects of thickness normalization and chemically induced damage were systematically evaluated. Results: Thickness normalization substantially reduced variability in melatonin Papp, particularly within same-animal comparisons, thereby improving statistical power and data reliability. In contrast, Flu-Na exhibited inconsistent correlations across different pigs and failed to reflect the expected increase in permeability following isopropyl alcohol (IPA)-induced epithelial damage. These results suggest that the relationship between epithelial injury and paracellular transport may be non-linear and not universally applicable under ex vivo conditions, limiting the suitability of Flu-Na as a standalone marker of mucosal integrity. Conclusions: The findings highlight the importance of integrating mucosal thickness correction into standardized experimental protocols and call for a critical reassessment of Flu-Na in nasal drug delivery research. Full article
(This article belongs to the Section Pharmaceutical Technology)
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58 pages, 1833 KiB  
Review
Animal Models of Pathogenic New World Arenaviruses
by Alexander V. Alvarado, Robert W. Cross, Thomas W. Geisbert and Courtney Woolsey
Microorganisms 2025, 13(6), 1358; https://doi.org/10.3390/microorganisms13061358 - 11 Jun 2025
Viewed by 537
Abstract
Since the emergence of Junín virus in 1953, pathogenic New World arenaviruses have remained a public health concern. These viruses, which also include Machupo virus, Guanarito virus, Sabiá virus, and Chapare virus, cause acute viral hemorrhagic fever and neurological complications, resulting in significant [...] Read more.
Since the emergence of Junín virus in 1953, pathogenic New World arenaviruses have remained a public health concern. These viruses, which also include Machupo virus, Guanarito virus, Sabiá virus, and Chapare virus, cause acute viral hemorrhagic fever and neurological complications, resulting in significant morbidity and mortality. Given the dearth of licensed therapeutics or vaccines against these pathogens, animal models of infection that recapitulate human manifestations of disease remain critically important to the development of efficacious medical countermeasures. Rodents and non-human primates have been successfully used to model human New World arenaviral infections, with guinea pigs, rhesus macaques, and cynomolgus macaques being the most successful models of infection for most major pathogenic New World arenaviruses. Here, we provide a highly comprehensive review of publicly reported animal models of pathogenic New World arenavirus infections, with a discussion of advantages and disadvantages for each model. Full article
(This article belongs to the Special Issue Animal Viral Infectious Diseases)
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