Application of Animal Models: From Physiology to Pathology

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Animals animals	2.7	4.9	2011	16.1 Days	CHF 2400	Submit
Cells cells	5.1	9.9	2012	17 Days	CHF 2700	Submit
Life life	3.2	4.3	2011	17.8 Days	CHF 2600	Submit
Veterinary Sciences vetsci	2.0	2.9	2014	21.2 Days	CHF 2100	Submit

18 pages, 8191 KiB

Open AccessArticle

IL-1β Induced Intestinal Inflammation Pathogenesis in East Friesian Sheep: Insights from Organoid Modeling

by Yue Xue, Yulong Zhao, Shuo Yan, Ruilin Du, Huiming Zhang, Wenna Yao, Teligun Bao, Fei Pan, Siqin Bao, Xihe Li and Yongli Song

Animals 2025, 15(8), 1097; https://doi.org/10.3390/ani15081097 - 10 Apr 2025

Viewed by 388

Abstract

Establishing an appropriate model of intestinal inflammation in vitro is crucial for studying the pathogenesis of inflammatory bowel disease (IBD). While immortalized cell lines have long been employed to investigate intestinal cell functions and host-pathogen interactions in sheep, they inadequately mimic the physiological [...] Read more.

Establishing an appropriate model of intestinal inflammation in vitro is crucial for studying the pathogenesis of inflammatory bowel disease (IBD). While immortalized cell lines have long been employed to investigate intestinal cell functions and host-pathogen interactions in sheep, they inadequately mimic the physiological characteristics of ovine intestinal inflammation and may lose critical genetic features. The emergence of organoids has revolutionized in vitro intestinal inflammation modeling by offering superior structural and functional fidelity to native tissues. In this study, we developed an IL-1β-induced intestinal inflammation organoid model derived from East Friesian sheep ileal crypts. Our data demonstrate that treatment with 30 ng/mL IL-1β significantly increased inflammatory factor secretion, the apoptosis of intermediate cells, and disrupted barrier integrity while simultaneously reducing bud formation capacity, organoid area, and stem cell proliferation. RNA-seq analysis revealed that IL-1β activated the NF-κB/TNF/IL-17 signaling pathway in intestinal organoids, thereby orchestrating the inflammatory response. This study establishes a novel sheep-derived intestinal inflammation organoid model, providing a physiologically relevant platform to investigate intestinal inflammation pathogenesis. These findings offer a translational tool for advancing drug development and pharmacological mechanism exploration in ovine intestinal inflammation research. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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19 pages, 5879 KiB

Open AccessArticle

Therapeutic Assessment of Diverse Doxycycline-Based Formulations in Promoting Deep Corneal Wound Healing: Evidence from a Rat Model

by Sze-Min Chan, Ching-Li Tseng, Wei-Hsiang Huang and Chung-Tien Lin

Vet. Sci. 2025, 12(2), 143; https://doi.org/10.3390/vetsci12020143 - 8 Feb 2025

Viewed by 642

Abstract

Doxycycline (Dxy), a broad-spectrum antibiotic with anti-inflammatory effects, is commonly used in ophthalmology but is unstable as a topical eyedrop, degrading quickly into inactive forms and requiring frequent application. To address this, gelatin nanoparticles (GNPs) loaded with Dxy (DNPs) were developed as a [...] Read more.

Doxycycline (Dxy), a broad-spectrum antibiotic with anti-inflammatory effects, is commonly used in ophthalmology but is unstable as a topical eyedrop, degrading quickly into inactive forms and requiring frequent application. To address this, gelatin nanoparticles (GNPs) loaded with Dxy (DNPs) were developed as a stable ophthalmic nanomedicine for enhancing corneal wound healing by inhibiting matrix metalloproteinases (MMPs). In this study, female Sprague–Dawley rats underwent lamellar keratectomy, and various Dxy formulations—oral, conventional eyedrops, and DNP-containing eyedrops—were evaluated for corneal wound repair. Clinical assessments included fluorescein staining, slit-lamp biomicroscopy, spectral-domain optical coherence tomography (SD-OCT) imaging, histopathology, and immunohistochemistry for MMP-2, MMP-9, and α-SMA. The DNP group (0.01% Dxy in DNPs, applied twice daily) demonstrated faster corneal thickness recovery and epithelial healing on days 7 and 14 compared to 0.1% Dxy eyedrop treatments applied twice or four times daily. DNP-treated eyes also showed reduced angiogenesis intensity and lower MMP-2 and MMP-9 immunoreactive scores, with enhanced stromal recovery and reduced neovascularization. These results highlight DNPs’ potential as a superior treatment for corneal wounds, providing effective healing with less frequent dosing and lower drug concentrations. This study supports DNPs’ potential for clinical application as a stable and efficient therapeutic agent in ophthalmology. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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17 pages, 7456 KiB

Open AccessArticle

Assessing Heat Resistance and Selecting Heat-Resistant Individuals of Largemouth Bass (Micropterus salmoides) with Tiered Thermal Exposure

by Haijie Chen, Hui Qiao, Zhicheng Xv, Guili Song, Shuning Liu, Cheng Luo, Yong Long and Shimei Lin

Animals 2025, 15(2), 128; https://doi.org/10.3390/ani15020128 - 8 Jan 2025

Viewed by 708

Abstract

Largemouth bass (LMB, Micropterus salmoides), a commercially important farmed fish, is vulnerable to heat stress. Breeding heat-resistant LMB is highly desirable in the face of global warming. However, we still lack an efficient method to assess the heat resistance of LMB. In [...] Read more.

Largemouth bass (LMB, Micropterus salmoides), a commercially important farmed fish, is vulnerable to heat stress. Breeding heat-resistant LMB is highly desirable in the face of global warming. However, we still lack an efficient method to assess the heat resistance of LMB. In this study, the critical thermal maximum (CTmax) and static exposure methods were first performed to assess the heat resistance of LMB juveniles. The CTmax values of the experimental fish (average body weight 9.87 ± 3.14 g) ranged from 39 to 40 °C but were too close together to differentiate the individual heat resistance. Static exposure experiments with varying temperatures and fish groups also did not provide a clear method for determining the heat resistance. To address these limitations, we developed a tiered exposure method, where the temperature was increased step-wise, starting from 28 to 34 °C at 2 °C increments and then at 0.5 °C increments above 34 °C, with each step lasting one day. The heat resistance of the fish was quantified as the lethal cumulative temperature (LCT), allowing for the classification of fish as sensitive or resistant to heat stress based on their LCT values. To correlate the changes in tissue structure and gene expression with the heat resistance, a new batch of LMB juveniles (average body weight 23.66 ± 6.98 g) were subjected to tiered heat exposure. Brain and liver tissues were collected from the control (without heat exposure), resistant and sensitive (still alive but demonstrated abnormal symptoms) individuals when the temperature was maintained at 35.5 °C for 24 h. The liver tissues of the heat-sensitive individuals showed significant damage and increased cell apoptosis (p < 0.05) relative to those of the resistant ones. The ddit3/chop, bax and casp3 genes demonstrated differential expressions in the liver of the sensitive and resistant fish. Additionally, the LMB juveniles (average body weight 84.06 ± 20.95 g) were found to be more heat resistant than the adults from different sources (average body weight 364.29 ± 84.43 g and 545.71 ± 184.56 g). Through the tiered exposure method, extremely heat-resistant individuals were successfully selected from the population (average body weight 22.69 ± 6.89 g). These findings provide valuable insights into the thermal biology of LMB and the potential for breeding heat-resistant LMB varieties. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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14 pages, 2172 KiB

Open AccessArticle

Cytotoxicity and Immunomodulatory Effects of Cannabidiol on Canine PBMCs: A Study in LPS-Stimulated and Epileptic Dogs

by Phannicha Kosukwatthana, Oumaporn Rungsuriyawiboon, Jatuporn Rattanasrisomporn, Kanogwan Kimram and Natthasit Tansakul

Animals 2024, 14(24), 3683; https://doi.org/10.3390/ani14243683 - 20 Dec 2024

Viewed by 1414

Abstract

Cannabidiol, the primary non-psychoactive phytocannabinoid found in cannabis, has generated significant research interest due to its potential for biological effects, such as anti-inflammatory, analgesic, immunomodulatory, and anticonvulsant properties. Several studies have demonstrated the potential of CBD to alter inflammatory cytokines; however, data on [...] Read more.

Cannabidiol, the primary non-psychoactive phytocannabinoid found in cannabis, has generated significant research interest due to its potential for biological effects, such as anti-inflammatory, analgesic, immunomodulatory, and anticonvulsant properties. Several studies have demonstrated the potential of CBD to alter inflammatory cytokines; however, data on CBD’s effects on cell viability and pro-inflammatory cytokines in target animals, such as dogs, are limited. Therefore, in this study, we investigated the effects of CBD on the cell viability and modulation of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α), in canine PBMCs stimulated with LPS. To evaluate the effect of CBD on neuroinflammation in epilepsy pathology, an independent study of five refractory epileptic dogs co-treated with CBD for 30 days was conducted. The current findings revealed that CBD concentrations of 16 µg/mL had a statistically significant effect on the viability of canine PBMCs with a calculated IC₅₀ of 15.54 µg/mL. The effect of CBD on inflammatory cytokines in LPS-stimulated PBMCs tended to be dose-dependent, with CBD concentrations of 5–30 μg/mL resulting in decreased production of the tested pro-inflammatory cytokines. Considering the effect of CBD on cytokine production by PBMCs from epileptic dogs, CBD has the potential to modulate immune responses and provide benefits when used in combination with antiepileptic drugs. The findings provided evidence of CBD cytotoxicity and its effect on the alteration of pro-inflammatory cytokines in canine PBMCs. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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14 pages, 1342 KiB

Open AccessArticle

Common Bed Bugs: Non-Viable Hosts for Trypanosoma rangeli Parasites

by Sanam Meraj, Phillip Phung, Kelvin Lau, Carl Lowenberger and Gerhard Gries

Cells 2024, 13(24), 2042; https://doi.org/10.3390/cells13242042 - 11 Dec 2024

Viewed by 958

Abstract

The hemoflagellate parasite Trypanosoma rangeli is transmitted by triatomine kissing bugs and may co-infect humans together with its Chagas disease-causing congener T. cruzi. Using real-time quantitative polymerase chain reaction (RT-qPCR) and antimicrobial assays, we studied (i) the temporal and spatial [...] Read more.

The hemoflagellate parasite Trypanosoma rangeli is transmitted by triatomine kissing bugs and may co-infect humans together with its Chagas disease-causing congener T. cruzi. Using real-time quantitative polymerase chain reaction (RT-qPCR) and antimicrobial assays, we studied (i) the temporal and spatial distribution of T. rangeli in common bed bugs, Cimex lectularius, following oral ingestion and hemocoelic injection of T. rangeli, and (ii) the immune responses of bed bugs induced by T. rangeli infections. Irrespective of infection mode, no live T. rangeli were present in the bed bugs’ hemolymph, salivary glands, or feces. On day 1 following infection, the bed bugs strongly upregulated the antimicrobial peptide CL-defensin. Following hemocoelic injection of T. rangeli, live parasites were absent in any bed bug tissues examined throughout the 10-day study period. The ingestion of T. rangeli-infected blood had no significant effect on bed bug survival. Our findings indicate that bed bugs disable the development of T. rangeli within their body, in stark contrast to triatomine kissing bugs, which allow the development and transmission of T. rangeli. Our findings help unravel the intricate relationships between bed bugs and trypanosomes, and they contribute to our understanding of vector biology. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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30 pages, 2451 KiB

Open AccessReview

Animal Models of Febrile Seizures: Limitations and Recent Advances in the Field

by Alexandra V. Griflyuk, Tatyana Y. Postnikova and Aleksey V. Zaitsev

Cells 2024, 13(22), 1895; https://doi.org/10.3390/cells13221895 - 16 Nov 2024

Cited by 3 | Viewed by 1248

Abstract

Febrile seizures (FSs) are defined as seizures occurring in children aged 6 months to 5 years with a background of elevated body temperature. It is one of the most common neurological disorders of childhood, emphasizing the importance of understanding the causes of FSs [...] Read more.

Febrile seizures (FSs) are defined as seizures occurring in children aged 6 months to 5 years with a background of elevated body temperature. It is one of the most common neurological disorders of childhood, emphasizing the importance of understanding the causes of FSs and their impact on the developing nervous system. However, there are significant limitations to the technologies currently available for studying the etiology and pathophysiology of seizures in humans. It is currently not possible to adequately capture the subtle molecular and structural rearrangements of the nervous system that can occur after seizures in humans. The use of animal models can be invaluable for these purposes. The most commonly used models in modern research are hyperthermic models in rats and mice aged 10–12 days. While these models can reproduce many of the characteristics of FSs, they have certain limitations. This review outlines the key considerations when working with models of FSs, provides an overview of current approaches to producing seizures in different model subjects, and presents a summary of key findings regarding morphological and functional changes in the brain and behavioral alterations that have been identified in studies using animal models of FSs. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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17 pages, 5353 KiB

Open AccessArticle

Biomechanical Evaluation of a Novel Ceramic Implant for Canine Cranial Cruciate Ligament Rupture Treatment: A Finite Element Analysis Approach

by Mark Leon Lang, Matthias Lüpke, Maximilian Götz, Holger A. Volk, Jan Klasen and Oliver Harms

Animals 2024, 14(22), 3296; https://doi.org/10.3390/ani14223296 - 15 Nov 2024

Viewed by 832

Abstract

This research investigates the biomechanical effects of a novel ceramic implant for the treatment of canine cranial cruciate ligament rupture (CCLR) based on the tibial tuberosity advancement (TTA) method using finite element analysis (FEA). A 3D FEA of the tibiofemoral joint simulating the [...] Read more.

This research investigates the biomechanical effects of a novel ceramic implant for the treatment of canine cranial cruciate ligament rupture (CCLR) based on the tibial tuberosity advancement (TTA) method using finite element analysis (FEA). A 3D FEA of the tibiofemoral joint simulating the applied forces (44.5% of body weight) during the mid-stance phase (joint angle 135°) of the dog’s stride was performed. Three conditions were considered for each joint: the physiological condition, the pathological condition with CCLR and the restored condition after TTA. Eight cadavers were used to create fifteen paired knee joints. The results showed significant differences in the forces that could be measured in the patellar tendon (PT) and in the cranial displacement of the tibial tuberosity between the conditions. The PT forces increased in the pathological state and continued to increase in the restored state, while the cranial displacement of the tibial tuberosity increased in the pathological state and decreased again in the restored state. Correlation analyses revealed significant correlations between PT forces, body weight and cranial displacement. The FEA provides initial insights into the force distribution and functionality of the ceramic implant. However, further testing is required to validate reliability and evaluate the efficacy of the implant. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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21 pages, 5888 KiB

Open AccessArticle

A Novel Non-Invasive Murine Model of Neonatal Hypoxic-Ischemic Encephalopathy Demonstrates Developmental Delay and Motor Deficits with Activation of Inflammatory Pathways in Monocytes

by Elise A. Lemanski, Bailey A. Collins, Andrew T. Ebenezer, Sudha Anilkumar, Victoria A. Langdon, Qi Zheng, Shanshan Ding, Karl Royden Franke, Jaclyn M. Schwarz and Elizabeth C. Wright-Jin

Cells 2024, 13(18), 1551; https://doi.org/10.3390/cells13181551 - 14 Sep 2024

Cited by 1 | Viewed by 2433

Abstract

Neonatal hypoxic-ischemic encephalopathy (HIE) occurs in 1.5 per 1000 live births, leaving affected children with long-term motor and cognitive deficits. Few animal models of HIE incorporate maternal immune activation (MIA) despite the significant risk MIA poses to HIE incidence and diagnosis. Our non-invasive [...] Read more.

Neonatal hypoxic-ischemic encephalopathy (HIE) occurs in 1.5 per 1000 live births, leaving affected children with long-term motor and cognitive deficits. Few animal models of HIE incorporate maternal immune activation (MIA) despite the significant risk MIA poses to HIE incidence and diagnosis. Our non-invasive model of HIE pairs late gestation MIA with postnatal hypoxia. HIE pups exhibited a trend toward smaller overall brain size and delays in the ontogeny of several developmental milestones. In adulthood, HIE animals had reduced strength and gait deficits, but no difference in speed. Surprisingly, HIE animals performed better on the rotarod, an assessment of motor coordination. There was significant upregulation of inflammatory genes in microglia 24 h after hypoxia. Single-cell RNA sequencing (scRNAseq) revealed two microglia subclusters of interest following HIE. Pseudobulk analysis revealed increased microglia motility gene expression and upregulation of epigenetic machinery and neurodevelopmental genes in macrophages following HIE. No sex differences were found in any measures. These results support a two-hit noninvasive model pairing MIA and hypoxia as a model for HIE in humans. This model results in a milder phenotype compared to established HIE models; however, HIE is a clinically heterogeneous injury resulting in a variety of outcomes in humans. The pathways identified in our model of HIE may reveal novel targets for therapy for neonates with HIE. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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5 pages, 337 KiB

Open AccessCommunication

The Influence of Specific Pathogen-Free and Conventional Environments on the Hematological Parameters of Pigs Bred for Xenotransplantation

by Won Kil Lee, Hwi-Cheul Lee, Seunghoon Lee, Haesun Lee, Sang Eun Kim, Minguk Lee, Jin-Gu No, Keon Bong Oh and Poongyeon Lee

Life 2024, 14(9), 1132; https://doi.org/10.3390/life14091132 - 8 Sep 2024

Viewed by 1013

Abstract

Blood analysis plays a pivotal role in assessing the health of laboratory animals, including pigs. This study investigated the hematological profiles of transgenic pigs of the MGH breed for xenotransplantation, focusing on the effect of housing conditions on blood parameters. A cohort of [...] Read more.

Blood analysis plays a pivotal role in assessing the health of laboratory animals, including pigs. This study investigated the hematological profiles of transgenic pigs of the MGH breed for xenotransplantation, focusing on the effect of housing conditions on blood parameters. A cohort of pigs was longitudinally monitored from 6 to 18 months of age in both conventional and specific pathogen-free (SPF) environments. Red blood cells (RBCs), hemoglobin (HGB), and white blood cells (WBCs) were analyzed using standardized hematology analyzers. The results revealed that RBC and HGB levels were consistently higher in SPF-housed pigs. Notably, WBC counts were significantly lower in SPF-housed pigs, suggesting that reduced pathogen exposure under SPF conditions effectively diminished immune system activation. These findings raise a novel question as to whether distinct hematological parameters of specific and/or designated PF pigs would be advantages for the success of clinical xenotransplantation trials. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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12 pages, 936 KiB

Open AccessReview

A Comparative Review of Cytokines and Cytokine Targeting in Sepsis: From Humans to Horses

by Kallie J. Hobbs, Rosemary Bayless and M. Katie Sheats

Cells 2024, 13(17), 1489; https://doi.org/10.3390/cells13171489 - 5 Sep 2024

Cited by 2 | Viewed by 2135

Abstract

With the emergence of COVID-19, there is an increased focus in human literature on cytokine production, the implications of cytokine overproduction, and the development of novel cytokine-targeting therapies for use during sepsis. In addition to viral infections such as COVID-19, bacterial infections resulting [...] Read more.

With the emergence of COVID-19, there is an increased focus in human literature on cytokine production, the implications of cytokine overproduction, and the development of novel cytokine-targeting therapies for use during sepsis. In addition to viral infections such as COVID-19, bacterial infections resulting in exposure to endotoxins and exotoxins in humans can also lead to sepsis, resulting in organ failure and death. Like humans, horses are exquisitely sensitive to endotoxin and are among the veterinary species that develop clinical sepsis similar to humans. These similarities suggest that horses may serve as a naturally occurring model of human sepsis. Indeed, evidence shows that both species experience cytokine dysregulation, severe neutropenia, the formation of neutrophil extracellular traps, and decreased perfusion parameters during sepsis. Sepsis treatments that target cytokines in both species include hemoperfusion therapy, steroids, antioxidants, and immunomodulation therapy. This review will present the shared cytokine physiology across humans and horses as well as historical and updated perspectives on cytokine-targeting therapy. Finally, this review will discuss the potential benefits of increased knowledge of equine cytokine mechanisms and their potential positive impact on human medicine. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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11 pages, 4276 KiB

Open AccessArticle

Inhibitor of FTO, Rhein, Restrains the Differentiation of Myoblasts and Delays Skeletal Muscle Regeneration

by Rongyang Li, Yan Cao, Wangjun Wu, Honglin Liu and Shiyong Xu

Animals 2024, 14(16), 2434; https://doi.org/10.3390/ani14162434 - 22 Aug 2024

Viewed by 1037

Abstract

N6-methyladenosine (m6A) is a crucial RNA modification affecting skeletal muscle development. Rhein, an anti-inflammatory extract, inhibits FTO, a key demethylase in m6A metabolism. Our study showed that during muscle fiber formation, FTO and ALKBH5 expression increased while m6A levels decreased. After muscle [...] Read more.

N6-methyladenosine (m6A) is a crucial RNA modification affecting skeletal muscle development. Rhein, an anti-inflammatory extract, inhibits FTO, a key demethylase in m6A metabolism. Our study showed that during muscle fiber formation, FTO and ALKBH5 expression increased while m6A levels decreased. After muscle injury, FTO and ALKBH5 expression initially rose but later fell, while m6A levels initially dropped and then recovered. Inhibition of FTO by Rhein reduced MyHC and MyoG expression, indicating myoblast differentiation suppression. In a mouse model, Rhein decreased MyHC expression and muscle fiber cross-sectional area, delaying muscle regeneration. Rhein’s ability to increase RNA m6A modification delays skeletal muscle remodeling post-injury, suggesting a new medicinal application for this plant extract. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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17 pages, 1780 KiB

Open AccessArticle

A Dynamic Tool to Describe Lamb Growth and Its Use as a Decision Support System

by Rafael Marzall Amaral, Marcelo Teixeira Rodrigues, Erica Beatriz Schultz and Cristiano Eduardo Rodrigues Reis

Animals 2024, 14(15), 2246; https://doi.org/10.3390/ani14152246 - 2 Aug 2024

Viewed by 1219

Abstract

A dynamic model has been developed to simulate aspects of feedlot lamb growth and body composition, including energy and protein requirements, growth rate, composition of gain, and body mass. Model inputs include initial body mass (kg), standard final mass (kg), age (days), and [...] Read more.

A dynamic model has been developed to simulate aspects of feedlot lamb growth and body composition, including energy and protein requirements, growth rate, composition of gain, and body mass. Model inputs include initial body mass (kg), standard final mass (kg), age (days), and dietary energy concentration (Mcal·kg⁻¹). The model was assessed as a decision support tool using a dataset of 564 individual measures of final body mass and diet energy. The simulations provide graphical and numerical descriptions of nutrient requirements, composition of gain, and estimates of animal performance over time. The model is accurate and precise, with a root mean squared error of 7.79% of the observed final body mass and a coefficient of determination of 0.89 when simulating the same variable. The model can be used as a reliable decision support tool to estimate final body mass and the days on feed required to reach a certain final mass with precision and accuracy. Moreover, the dynamic model can also serve as a learning tool to illustrate practical principles of animal nutrition, nutrient requirement relationships, and body composition changes. This model holds the potential to enhance livestock management practices and assist producers in making informed decisions about feedlot lamb production. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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14 pages, 1178 KiB

Open AccessArticle

Pig Weight Estimation Method Based on a Framework Combining Mask R-CNN and Ensemble Regression Model

by Sheng Jiang, Guoxu Zhang, Zhencai Shen, Ping Zhong, Junyan Tan and Jianfeng Liu

Animals 2024, 14(14), 2122; https://doi.org/10.3390/ani14142122 - 20 Jul 2024

Cited by 3 | Viewed by 2072

Abstract

Using computer vision technology to estimate pig live weight is an important method to realize pig welfare. But there are two key issues that affect pigs’ weight estimation: one is the uneven illumination, which leads to unclear contour extraction of pigs, and the [...] Read more.

Using computer vision technology to estimate pig live weight is an important method to realize pig welfare. But there are two key issues that affect pigs’ weight estimation: one is the uneven illumination, which leads to unclear contour extraction of pigs, and the other is the bending of the pig body, which leads to incorrect pig body information. For the first one, Mask R-CNN was used to extract the contour of the pig, and the obtained mask image was converted into a binary image from which we were able to obtain a more accurate contour image. For the second one, the body length, hip width and the distance from the camera to the pig back were corrected by XGBoost and actual measured information. Then we analyzed the rationality of the extracted features. Three feature combination strategies were used to predict pig weight. In total, 1505 back images of 39 pigs obtained using Azure kinect DK were used in the numerical experiments. The highest prediction accuracy is XGBoost, with an MAE of 0.389, RMSE of 0.576, MAPE of 0.318% and

R^{2}

of 0.995. We also recommend using the Mask R-CNN + RFR method because it has fairly high precision in each strategy. The experimental results show that our proposed method has excellent performance in live weight estimation of pigs. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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15 pages, 2276 KiB

Open AccessArticle

Analysis of a Chronic Lateral Ankle Instability Model in the Rat: Conclusions and Suggestions for Future Research

by Ibrahim Saliba, Manon Bachy-Razzouk, Morad Bensidhoum, Thierry Hoc, Esther Potier, Raphaël Vialle and Alexandre Hardy

Life 2024, 14(7), 829; https://doi.org/10.3390/life14070829 - 28 Jun 2024

Viewed by 1281

Abstract

The purpose of this study was to evaluate potential osteoarthritic alterations within the ankle using a surgically-induced chronic lateral ankle instability (CLAI) model. Twelve rats were assigned randomly to either the control (n = 4) or CLAI group (n = 8). [...] Read more.

The purpose of this study was to evaluate potential osteoarthritic alterations within the ankle using a surgically-induced chronic lateral ankle instability (CLAI) model. Twelve rats were assigned randomly to either the control (n = 4) or CLAI group (n = 8). Surgery was performed on the right ankle. Osteoarthritis was assessed through in-vivo micro-CT at 8 weeks and a clinical analysis. Macroscopic analysis, high-resolution ex-vivo micro-CT and histological examination were conducted after euthanasia at 12 weeks. Three subgroups (SG) were analyzed. SG1 comprised the operated ankles of the CLAI group (n = 8). SG2 consisted of the non-operated ankles of the CLAI group (n = 8). SG3 included both sides of the control group (n = 8). In-vivo micro-CT revealed no significant differences among the three subgroups when analyzed together (p = 0.42), and when comparing SG1 with SG2 (p = 0.23) and SG3 (p = 0.43) individually. No noticeable clinical differences were observed. After euthanasia, macroscopic analysis employing OARSI score, did not demonstrate significant differences, except between the medial tibia of SG1 and SG3 (p = 0.03), and in the total score comparison between these two subgroups (p = 0.015). Ex-vivo micro-CT did not reveal any differences between the three subgroups regarding bony irregularities and BV/TV measurements (SG1 vs. SG2 vs. SG3: p = 0.72; SG1 vs. SG2: p = 0.80; SG1 vs. SG3: p = 0.72). Finally, there was no difference between the three subgroups regarding OARSI histologic score (p = 0.27). These findings indicate that the current model failed to induce significant osteoarthritis. However, they lay the groundwork for improving the model’s effectiveness and expanding its use in CLAI research, aiming to enhance understanding of this pathology and reduce unnecessary animal sacrifice. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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23 pages, 877 KiB

Open AccessReview

Electrophysiology Methods for Assessing of Neurodegenerative and Post-Traumatic Processes as Applied to Translational Research

by Rezeda Ramilovna Shigapova and Yana Olegovna Mukhamedshina

Life 2024, 14(6), 737; https://doi.org/10.3390/life14060737 - 7 Jun 2024

Cited by 1 | Viewed by 1834

Abstract

Electrophysiological studies have long established themselves as reliable methods for assessing the functional state of the brain and spinal cord, the degree of neurodegeneration, and evaluating the effectiveness of therapy. In addition, they can be used to diagnose, predict functional outcomes, and test [...] Read more.

Electrophysiological studies have long established themselves as reliable methods for assessing the functional state of the brain and spinal cord, the degree of neurodegeneration, and evaluating the effectiveness of therapy. In addition, they can be used to diagnose, predict functional outcomes, and test the effectiveness of therapeutic and rehabilitation programs not only in clinical settings, but also at the preclinical level. Considering the urgent need to develop potential stimulators of neuroregeneration, it seems relevant to obtain objective data when modeling neurological diseases in animals. Thus, in the context of the application of electrophysiological methods, not only the comparison of the basic characteristics of bioelectrical activity of the brain and spinal cord in humans and animals, but also their changes against the background of neurodegenerative and post-traumatic processes are of particular importance. In light of the above, this review will contribute to a better understanding of the results of electrophysiological assessment in neurodegenerative and post-traumatic processes as well as the possibility of translating these methods from model animals to humans. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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18 pages, 8381 KiB

Open AccessArticle

Inhibition of PIKfyve Leads to Lysosomal Disorders via Dysregulation of mTOR Signaling

by Jianhong Xia, Haiyun Wang, Zhihang Zhong and Jun Jiang

Cells 2024, 13(11), 953; https://doi.org/10.3390/cells13110953 - 30 May 2024

Cited by 1 | Viewed by 1825

Abstract

PIKfyve is an endosomal lipid kinase that synthesizes phosphatidylinositol 3,5-biphosphate from phosphatidylinositol 3-phsphate. Inhibition of PIKfyve activity leads to lysosomal enlargement and cytoplasmic vacuolation, attributed to impaired lysosomal fission processes and homeostasis. However, the precise molecular mechanisms underlying these effects remain a topic [...] Read more.

PIKfyve is an endosomal lipid kinase that synthesizes phosphatidylinositol 3,5-biphosphate from phosphatidylinositol 3-phsphate. Inhibition of PIKfyve activity leads to lysosomal enlargement and cytoplasmic vacuolation, attributed to impaired lysosomal fission processes and homeostasis. However, the precise molecular mechanisms underlying these effects remain a topic of debate. In this study, we present findings from PIKfyve-deficient zebrafish embryos, revealing enlarged macrophages with giant vacuoles reminiscent of lysosomal storage disorders. Treatment with mTOR inhibitors or effective knockout of mTOR partially reverses these abnormalities and extend the lifespan of mutant larvae. Further in vivo and in vitro mechanistic investigations provide evidence that PIKfyve activity is essential for mTOR shutdown during early zebrafish development and in cells cultured under serum-deprived conditions. These findings underscore the critical role of PIKfyve activity in regulating mTOR signaling and suggest potential therapeutic applications of PIKfyve inhibitors for the treatment of lysosomal storage disorders. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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14 pages, 2220 KiB

Open AccessArticle

A Comparative Analysis of the Cytotoxic and Vascular Activity Effects of Western Diamondback Rattlesnake (Crotalus atrox) and Eastern Diamondback Rattlesnake (Crotalus adamanteus) Venoms Using a Chick Embryo Model

by Barbora Bekešová, Vladimír Petrilla, Magdaléna Polláková, Zuzana Andrejčáková, Radoslava Vlčková, Barbara Dyba, Drahomíra Sopková, Monika Petrillová, Eva Petrovová and Jaroslav Legáth

Animals 2024, 14(11), 1634; https://doi.org/10.3390/ani14111634 - 30 May 2024

Viewed by 1247

Abstract

Crotalus snakebites induce various toxicological effects, encompassing neurological, myotoxic, and cytotoxic symptoms, with potentially fatal outcomes. Investigating venom toxicity is essential for public health, and developing new tools allows for these effects to be studied more comprehensively. The research goals include the elucidation [...] Read more.

Crotalus snakebites induce various toxicological effects, encompassing neurological, myotoxic, and cytotoxic symptoms, with potentially fatal outcomes. Investigating venom toxicity is essential for public health, and developing new tools allows for these effects to be studied more comprehensively. The research goals include the elucidation of the physiological consequences of venom exposure and the assessment of toxicity using animal models. Chicken embryos serve as valuable models for assessing venom toxicity through the chick embryotoxicity screening test (CHEST) and the chick chorioallantoic membrane (CAM) assay, particularly useful for evaluating vascular impacts. C. adamanteus venom application resulted in higher embryotoxicity and morphological abnormalities, such as Siamese twins. The CAM assay demonstrated the hemorrhagic effects of venom, varying with venom type and concentration. The irritant potential of both venom types was classified as slight or moderate depending on their concentration. Additionally, acetylcholinesterase (AChE) activity was performed to receive information about organ toxicity. The results show that both venoms induced changes in the whole embryo, heart, and liver weights, but the C. adamanteus venom was identified as more toxic. Specific venom concentrations affected AChE activity in embryonic tissues. These findings underscore the embryotoxic and vasoactive properties of Crotalus venoms, providing valuable insights into their mechanisms of toxicity and potential applications in biomedicine. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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11 pages, 2552 KiB

Open AccessArticle

Transcutaneous Auricular Vagal Nerve Stimulation in Healthy Non-Sedated Horses: A Feasibility Study

by Valentina Vitale, Francesca Bindi, Ana Velloso Alvarez, María de la Cuesta-Torrado, Giulia Sala and Micaela Sgorbini

Vet. Sci. 2024, 11(6), 241; https://doi.org/10.3390/vetsci11060241 - 28 May 2024

Viewed by 2314

Abstract

This study aimed to evaluate the feasibility of transcutaneous auricular vagal nerve stimulation (tAVNS) in healthy horses and its effect on heart rate variability (HRV). The study comprised three phases: the selection of mares, their acclimatization to the tAVNS, and the stimulation phase. [...] Read more.

This study aimed to evaluate the feasibility of transcutaneous auricular vagal nerve stimulation (tAVNS) in healthy horses and its effect on heart rate variability (HRV). The study comprised three phases: the selection of mares, their acclimatization to the tAVNS, and the stimulation phase. Stimulation was performed with two electrodes positioned on the right pinna. The settings were 0.5 mA, 250 μs, and 25 Hz for pulse amplitude, pulse width, and pulse frequency, respectively. HRV was analysed before (B1), during (T), and after (B2) the tAVNS. From the 44 mares initially included, only 7 completed the three phases. In these mares, the heart rate (HR) was significantly lower, and frequency domain parameters showed an increased parasympathetic tone in B2 compared with B1. However, in 3/7 mares, the HR was significantly higher during T compared with B1 and B2, compatible with a decreased parasympathetic tone, while in 4/7 mares, the HR was significantly lower and the parasympathetic nervous system index was significantly higher during T and B2 compared with B1. The tAVNS is an economical and easy procedure to perform and has the potential to stimulate vagal activity; however, it was poorly tolerated in the mares included in this study. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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15 pages, 4790 KiB

Open AccessArticle

Interaction between Chromodomain Y-like Protein and Androgen Receptor Signaling in Sertoli Cells Accounts for Spermatogenesis

by Kuo-Chung Lan, Yin-Hua Cheng, Yun-Chiao Chang, Kuo-Ting Wei, Pei-Ling Weng and Hong-Yo Kang

Cells 2024, 13(10), 851; https://doi.org/10.3390/cells13100851 - 16 May 2024

Viewed by 1341

Abstract

Spermatogenesis is a highly regulated process dependent on androgen receptor (AR) signaling in Sertoli cells. However, the pathogenic mechanisms of spermatogenic failure, by which loss of AR impairs downstream target genes to affect Sertoli cell function, remain incompletely understood. By using microarray analysis, [...] Read more.

Spermatogenesis is a highly regulated process dependent on androgen receptor (AR) signaling in Sertoli cells. However, the pathogenic mechanisms of spermatogenic failure, by which loss of AR impairs downstream target genes to affect Sertoli cell function, remain incompletely understood. By using microarray analysis, we identified several AR-regulated genes involved in the maturation of spermatogenesis, including chromodomain Y-like protein (CDYL) and transition proteins 1 (TNP-1), that were significantly decreased in ARKO mouse testes. AR and CDYL were found to co-localize and interact in Sertoli cells. The AR–CDYL complex bound to the promoter regions of TNP1 and modulated their transcriptional activity. CDYL acts as a co-regulator of AR transactivation, and its expression is decreased in the Sertoli cells of human testes from patients with azoospermia. The androgen receptor–chromodomain Y-like protein axis plays a crucial role in regulating a network of genes essential for spermatogenesis in Sertoli cells. Disruption of this AR–CDYL regulatory axis may contribute to spermatogenic failure. These findings provide insights into novel molecular mechanisms targeting the AR–CDYL signaling pathway, which may have implications for developing new therapeutic strategies for male infertility. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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8 pages, 801 KiB

Open AccessBrief Report

Fetal Alcohol Spectrum Disorder: The Honey Bee as a Social Animal Model

by Marcelo P. Camilli, Olena M. Simko, Breanne Bevelander, Jenna M. Thebeau, Fatima Masood, Marina C. Bezerra da Silva, Muhammad Fahim Raza, Sofiia Markova, Oleksii Obshta, Midhun S. Jose, Sarah Biganski, Ivanna V. Kozii, Michael W. Zabrodski, Igor Moshynskyy, Elemir Simko and Sarah C. Wood

Life 2024, 14(4), 434; https://doi.org/10.3390/life14040434 - 25 Mar 2024

Viewed by 2420

Abstract

Animal models have been essential for advancing research of fetal alcohol spectrum disorder (FASD) in humans, but few animal species effectively replicate the behavioural and clinical signs of FASD. The honey bee (Apis mellifera) is a previously unexplored research model for [...] Read more.

Animal models have been essential for advancing research of fetal alcohol spectrum disorder (FASD) in humans, but few animal species effectively replicate the behavioural and clinical signs of FASD. The honey bee (Apis mellifera) is a previously unexplored research model for FASD that offers the distinct benefit of highly social behaviour. In this study, we chronically exposed honey bee larvae to incremental concentrations of 0, 3, 6, and 10% ethanol in the larval diet using an in vitro rearing protocol and measured developmental time and survival to adult eclosion, as well as body weight and motor activity of newly emerged adult bees. Larvae reared on 6 and 10% dietary ethanol demonstrated significant, dose-responsive delays to pupation and decreased survival and adult body weight. All ethanol-reared adults showed significantly decreased motor activity. These results suggest that honey bees may be a suitable social animal model for future FASD research. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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17 pages, 5197 KiB

Open AccessArticle

Aerobic Exercise Modulates Proteomic Profiles in Gastrocnemius Muscle of db/db Mice, Ameliorating Sarcopenia

by Yen-Chun Huang, Monika Renuka Sanotra, Chi-Chang Huang, Yi-Ju Hsu and Chen-Chung Liao

Life 2024, 14(3), 412; https://doi.org/10.3390/life14030412 - 20 Mar 2024

Cited by 3 | Viewed by 2808

Abstract

Type-2 diabetes mellitus (T2DM)-induced sarcopenia is intertwined with diminished insulin sensitivity and extracellular matrix (ECM) remodeling in skeletal muscle and other organs. Physical activities such as aerobic exercise play a crucial role in regulating blood glucose levels, insulin sensitivity, metabolic pathways, oxidative stress, [...] Read more.

Type-2 diabetes mellitus (T2DM)-induced sarcopenia is intertwined with diminished insulin sensitivity and extracellular matrix (ECM) remodeling in skeletal muscle and other organs. Physical activities such as aerobic exercise play a crucial role in regulating blood glucose levels, insulin sensitivity, metabolic pathways, oxidative stress, fibrosis, ECM remodeling, and muscle regeneration by modulating differentially expressed protein (DEP) levels. The objectives of our research were to investigate the effect of six weeks of aerobic exercise on the gastrocnemius and soleus muscle of db/db mice’s DEP levels compared to those of sedentary db/db mice. A total of eight db/db mice were divided into two groups (n = 4 per group), namely sedentary mice (SED) and exercise-trained mice (ET), of which the latter were subjected to six weeks of a moderate-intensity aerobic exercise intervention for five days per week. After the exercise intervention, biochemical tests, including analyses of blood glucose and HbA1c levels, were performed. Histological analysis using H & E staining on tissue was performed to compare morphological characters. Gastrocnemius and soleus muscles were dissected and processed for proteomic analysis. Data were provided and analyzed based on the DEPs using the label-free quantification (LFQ) algorithm. Functional enrichment analysis and Ingenuity Pathway Analysis (IPA) were employed as bioinformatics tools to elucidate the molecular mechanisms involved in the DEPs and disease progression. Significantly reduced blood glucose and HbA1c levels and an increased cross-sectional area (CSA) of gastrocnemius muscle fibers were seen in the ET group after the exercise interventions due to upregulations of metabolic pathways. Using proteomics data analysis, we found a significant decrease in COL1A1, COL4A2, ENG, and LAMA4 protein levels in the ET gastrocnemius, showing a significant improvement in fibrosis recovery, ECM remodeling, and muscle regeneration via the downregulation of the TGF-β signaling pathway. Upregulated metabolic pathways due to ET-regulated DEPs in the gastrocnemius indicated increased glucose metabolism, lipid metabolism, muscle regeneration, and insulin sensitivity, which play a crucial role in muscle regeneration and maintaining blood glucose and lipid levels. No significant changes were observed in the soleus muscle due to the type of exercise and muscle fiber composition. Our research suggests that engaging in six weeks of aerobic exercise may have a positive impact on the recovery of T2DM-induced sarcopenia, which might be a potential candidate for mitigation, prevention, and therapeutic treatment in the future. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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14 pages, 1420 KiB

Open AccessArticle

Preliminary Proteomic Study of the Porcine Pituitary Gland under Heat Stress

by Qiu Zhou, Yuan Gao, Yin Li, Huili Xie, Xiaoxi Liu, Yanhong Yong, Youquan Li, Zhichao Yu, Xingbin Ma and Xianghong Ju

Life 2024, 14(3), 366; https://doi.org/10.3390/life14030366 - 11 Mar 2024

Viewed by 1531

Abstract

Although numerous studies have shown that the hypothalamic–pituitary–adrenal axis plays a vital role in the response to environmental stress by mediating the production of a series of hormones, the mechanism underlying these effects has not been elucidated. This study used proteomics techniques to [...] Read more.

Although numerous studies have shown that the hypothalamic–pituitary–adrenal axis plays a vital role in the response to environmental stress by mediating the production of a series of hormones, the mechanism underlying these effects has not been elucidated. This study used proteomics techniques to investigate the differentially expressed proteins (DEPs) in the pituitary glands of pigs and to elucidate the potential changes in the immune–neuroendocrine system under heat stress (HS). In total, 2517 peptides corresponding to 205 proteins were detected. A comparison of the expression patterns between HSs and healthy controls revealed 56 DEPs, of which 31 were upregulated and 25 were downregulated. Ingenuity pathway analysis (IPA) was used to reveal the subcellular characteristics, functional pathways, regulatory networks, and upstream regulators of the identified proteins. The results showed that these differentially expressed proteins were involved in intercellular communication, interactions, apoptosis, nervous system development, functions, abnormalities and other functions, and in the regulatory network. Moreover, the upstream regulators of the differentially expressed proteins were mainly transcriptional regulators, hormones, and cytokines. Thus, the functional network and pathway analyses could provide insights into the complexity and dynamics of HS–host interactions and may accelerate our understanding of the mechanisms underlying HS. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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17 pages, 6779 KiB

Open AccessArticle

Production of Proliferation- and Differentiation-Competent Porcine Myoblasts for Preclinical Studies in a Porcine Large Animal Model of Muscular Insufficiency

by Jasmin Knoll, Bastian Amend, Tanja Abruzzese, Niklas Harland, Arnulf Stenzl and Wilhelm K. Aicher

Life 2024, 14(2), 212; https://doi.org/10.3390/life14020212 - 31 Jan 2024

Cited by 1 | Viewed by 1492

Abstract

Muscular insufficiency is observed in many conditions after injury, chronic inflammation, and especially in elderly populations. Causative cell therapies for muscle deficiencies are not state of the art. Animal models to study the therapy efficacy are, therefore, needed. We developed an improved protocol [...] Read more.

Muscular insufficiency is observed in many conditions after injury, chronic inflammation, and especially in elderly populations. Causative cell therapies for muscle deficiencies are not state of the art. Animal models to study the therapy efficacy are, therefore, needed. We developed an improved protocol to produce myoblasts suitable for pre-clinical muscle therapy studies in a large animal model. Myoblasts were isolated from the striated muscle, expanded by employing five different protocols, and characterized on transcript and protein expression levels to determine procedures that yielded optimized regeneration-competent myoblasts and multi-nucleated myotubes. We report that swine skeletal myoblasts proliferated well under improved conditions without signs of cellular senescence, and expressed significant levels of myogenic markers including Pax7, MyoD1, Myf5, MyoG, Des, Myf6, CD56 (p ≤ 0.05 each). Upon terminal differentiation, myoblasts ceased proliferation and generated multi-nucleated myotubes. Injection of such myoblasts into the urethral sphincter complex of pigs with sphincter muscle insufficiency yielded an enhanced functional regeneration of this muscle (81.54% of initial level) when compared to the spontaneous regeneration in the sham controls without myoblast injection (67.03% of initial level). We conclude that the optimized production of porcine myoblasts yields cells that seem suitable for preclinical studies of cell therapy in a porcine large animal model of muscle insufficiency. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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13 pages, 1821 KiB

Open AccessArticle

Development of an Alternative In Vitro Rumen Fermentation Prediction Model

by Xinjie Wang, Jianzhao Zhou, Runjie Jiang, Yuxuan Wang, Yonggen Zhang, Renbiao Wu, Xiaohui A, Haitao Du, Jiaxu Tian, Xiaoli Wei and Weizheng Shen

Animals 2024, 14(2), 289; https://doi.org/10.3390/ani14020289 - 17 Jan 2024

Viewed by 2301

Abstract

The aim of this study is to identify an alternative approach for simulating the in vitro fermentation and quantifying the production of rumen methane and rumen acetic acid during the rumen fermentation process with different total mixed rations. In this experiment, dietary nutrient [...] Read more.

The aim of this study is to identify an alternative approach for simulating the in vitro fermentation and quantifying the production of rumen methane and rumen acetic acid during the rumen fermentation process with different total mixed rations. In this experiment, dietary nutrient compositions (neutral detergent fiber (NDF), acid detergent fiber (ADF), crude protein (CP), and dry matter (DM)) were selected as input parameters to establish three prediction models for rumen fermentation parameters (methane and acetic acid): an artificial neural network model, a genetic algorithm-bp model, and a support vector machine model. The research findings show that the three models had similar simulation results that aligned with the measured data trends (R² ≥ 0.83). Additionally, the root mean square errors (RMSEs) were ≤1.85 mL/g in the rumen methane model and ≤2.248 mmol/L in the rumen acetic acid model. Finally, this study also demonstrates the models’ capacity for generalization through an independent verification experiment, as they effectively predicted outcomes even when significant trial factors were manipulated. These results suggest that machine learning-based in vitro rumen models can serve as a valuable tool for quantifying rumen fermentation parameters, guiding the optimization of dietary structures for dairy cows, rapidly screening methane-reducing feed options, and enhancing feeding efficiency. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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