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21 pages, 3334 KiB  
Article
Protective Efficacy of Lactobacillus plantarum Postbiotic beLP-K in a Dexamethasone-Induced Sarcopenia Model
by Juyeong Moon, Jin-Ho Lee, Eunwoo Jeong, Harang Park, Hye-Yeong Song, Jinsu Choi, Min-ah Kim, Kwon-Il Han, Doyong Kim, Han Sung Kim and Tack-Joong Kim
Int. J. Mol. Sci. 2025, 26(15), 7504; https://doi.org/10.3390/ijms26157504 (registering DOI) - 3 Aug 2025
Abstract
Sarcopenia is characterized by a reduction in muscle function and skeletal muscle mass relative to that of healthy individuals. In older adults and those who are less resistant to sarcopenia, glucocorticoid secretion or accumulation during treatment exacerbates muscle protein degradation, potentially causing sarcopenia. [...] Read more.
Sarcopenia is characterized by a reduction in muscle function and skeletal muscle mass relative to that of healthy individuals. In older adults and those who are less resistant to sarcopenia, glucocorticoid secretion or accumulation during treatment exacerbates muscle protein degradation, potentially causing sarcopenia. This study assessed the preventive effects and mechanisms of heat-killed Lactobacillus plantarum postbiotic beLP-K (beLP-K) against dexamethasone (DEX)-induced sarcopenia in C2C12 myotubes and Sprague-Dawley rats. The administration of beLP-K did not induce cytotoxicity and mitigated cell damage caused by DEX. Furthermore, beLP-K significantly reduced the expression of forkhead box O3 α (FoxO3α), muscle atrophy f-box (MAFbx)/atrogin-1, and muscle RING-finger protein-1 (MuRF1), which are associated with muscle protein degradation. DEX induced weight loss in rats; however, in the beLP-K group, weight gain was observed. Micro-computed tomography analysis revealed that beLP-K increased muscle mass, correlating with weight and grip strength. beLP-K alleviated the DEX-induced reduction in grip strength and increased the mass of hind leg muscles. The correlation between beLP-K administration and increased muscle mass was associated with decreased expression levels of muscle degradation-related proteins such as MAFbx/atrogin-1 and MuRF1. Therefore, beLP-K may serve as a treatment for sarcopenia or as functional food material. Full article
(This article belongs to the Section Molecular Biology)
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18 pages, 1647 KiB  
Article
BRAF Mutation Analysis: A Retrospective Evaluation of 8365 Diagnostic Samples with a Special View on Canine Breeds (2018–2024)
by Marielle Appenzeller, Alexandra Kehl, Katrin Törner, Katharina Charlotte Jensen, Robert Klopfleisch and Heike Aupperle-Lellbach
Vet. Sci. 2025, 12(8), 729; https://doi.org/10.3390/vetsci12080729 (registering DOI) - 2 Aug 2025
Viewed by 126
Abstract
The BRAF V595E mutation analysis in canine urothelial carcinomas (UCs) has found its way into routine diagnostics, but no data analysis has been published until now. The present study aimed to estimate the distribution of age, sex, and breed in 8365 canine diagnostic [...] Read more.
The BRAF V595E mutation analysis in canine urothelial carcinomas (UCs) has found its way into routine diagnostics, but no data analysis has been published until now. The present study aimed to estimate the distribution of age, sex, and breed in 8365 canine diagnostic samples submitted for BRAF mutation analysis during 2018–2024. The specimens included 8215 urine samples, 17 cytological, and 133 histopathological specimens, and were submitted in cases of suspected UC, to rule out UC, or for screening purposes. All samples were tested for the BRAF V595E mutation using droplet digital PCR (ddPCR). The data were statistically analysed and logistic regression models (Odds Ratio (OR)) were calculated. Compared to samples from mixed-breed dogs, the specimens from Scottish Terriers (OR: 4.21), Shetland Sheepdogs (OR: 2.65), Beagles (OR: 2.33), Fox Terriers (OR: 1.92), Staffordshire Bull Terriers (OR: 1.86), Magyar Vizslas (OR: 1.77), Chihuahuas (OR: 1.70), and West Highland White Terriers (OR: 1.43) had a significantly increased probability of the presence of BRAF mutation indicating UC. The youngest BRAF-positive dogs of these predisposed breeds (n = 4) were 5 years old. In conclusion, screening tests in predisposed breeds may be recommended from the age of 5 years. Full article
(This article belongs to the Special Issue Focus on Tumours in Pet Animals: 2nd Edition)
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18 pages, 823 KiB  
Article
Influence of a Th17-Inducing Cytokine Milieu on Phenotypical and Functional Properties of Regulatory T Cells in Chronic Inflammatory Arthritis
by Tobias Schwarz, Giovanni Almanzar, Marie Wulfheide, Robert Woidich, Marie-Therese Holzer, Timotheos Christoforou, Leonie Karle, David Radtke, Franziska Brauneiser, Thomas Haaf, Ramya Potabattula, Gabriela Ortega, Klaus-Peter Lesch, Arne Schäfer, Sandrine Benoit, Astrid Schmieder, Matthias Goebeler, Marc Schmalzing, Martin Feuchtenberger and Martina Prelog
Int. J. Mol. Sci. 2025, 26(15), 7339; https://doi.org/10.3390/ijms26157339 - 29 Jul 2025
Viewed by 250
Abstract
Considering the high plasticity of FoxP3+ regulatory T (Treg) cells and Interleukin (IL)-17-producing Th17 cells, we hypothesized that a Th17 inflammatory milieu may impair the functional properties of Treg cells in chronic inflammatory arthritides. Therefore, a cross-sectional explorative analysis was set up [...] Read more.
Considering the high plasticity of FoxP3+ regulatory T (Treg) cells and Interleukin (IL)-17-producing Th17 cells, we hypothesized that a Th17 inflammatory milieu may impair the functional properties of Treg cells in chronic inflammatory arthritides. Therefore, a cross-sectional explorative analysis was set up in patients with psoriatic arthritis (PsoA), rheumatoid arthritis, or spondyloarthritis to investigate the features of Th17 and Treg cells. T cell subpopulation counts, FOXP3 mRNA expression, CpG methylation of the FOXP3 gene, and the suppressive capacity of isolated Treg cells were determined. Ex vivo analysis of PsoA-derived peripheral blood lymphocytes showed a Th17-mediated inflammation. It was accompanied by demethylation of the FOXP3 promotor and Treg-specific demethylated region (TSDR) in Treg cells which, however, resulted neither in elevated FOXP3 mRNA expression nor in increased suppressive Treg cell capacity. To clarify this conundrum, in vitro stimulation of isolated Treg cells with Th17-inducing cytokines (IL-1β, IL-6, IL-23, TGFβ), recombinant IL-17, or the anti-IL-17A antibody secukinumab was performed, demonstrating that cell culture conditions polarizing towards Th17, but not IL-17 itself, impair the suppressive function of Treg cells, accompanied by diminished FOXP3 mRNA expression due to hypermethylation of the FOXP3 promotor and TSDR. This potential causal relationship between Th17 inflammation and impaired Treg cell function requires attention regarding the development of immunomodulatory therapies. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapy in Autoimmune Disease)
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21 pages, 7017 KiB  
Article
Chronic Heat Stress Caused Lipid Metabolism Disorder and Tissue Injury in the Liver of Huso dauricus via Oxidative-Stress-Mediated Ferroptosis
by Yining Zhang, Yutao Li, Ruoyu Wang, Sihan Wang, Bo Sun, Dingchen Cao, Zhipeng Sun, Weihua Lv, Bo Ma and Ying Zhang
Antioxidants 2025, 14(8), 926; https://doi.org/10.3390/antiox14080926 - 29 Jul 2025
Viewed by 159
Abstract
High-temperature stress has become an important factor that has restricted the aquaculture industry. Huso dauricus is a high-economic-value fish that has faced the threat of thermal stress. Based on this point, our investigation aimed to explore the detailed mechanism of the negative impacts [...] Read more.
High-temperature stress has become an important factor that has restricted the aquaculture industry. Huso dauricus is a high-economic-value fish that has faced the threat of thermal stress. Based on this point, our investigation aimed to explore the detailed mechanism of the negative impacts of heat stress on the liver metabolism functions in Huso dauricus. In this study, we set one control group (19 °C) and four high-temperature treatment groups (22 °C, 25 °C, 28 °C, 31 °C) with 40 fish in each group for continuous 53-day heat exposure. Histological analysis, biochemical detection, and transcriptome technology were used to explore the effects of heat stress on the liver structure and functions of juvenile Huso dauricus. It suggested heat-stress-induced obvious liver injury and reactive oxygen species accumulation in Huso dauricus with a time/temperature-dependent manner. Serum total protein, transaminase, and alkaline phosphatase activities showed significant changes under heat stress (p < 0.05). In addition, 6433 differentially expressed genes (DEGs) were identified based on the RNA-seq project. Gene Ontology enrichment analysis showed that various DEGs could be mapped to the lipid-metabolism-related terms. KEGG enrichment and immunohistochemistry analysis showed that ferroptosis and FoxO signaling pathways were significantly enriched (p < 0.05). These results demonstrated that thermal stress induced oxidative stress damage in the liver of juvenile Huso dauricus, which triggered lipid metabolism disorder and hepatocyte ferroptosis to disrupt normal liver functions. In conclusion, chronic thermal stress can cause antioxidant capacity imbalance in the liver of Huso dauricus to mediate the ferroptosis process, which would finally disturb the lipid metabolism homeostasis. In further research, it will be necessary to verify the detailed cellular signaling pathways that are involved in the heat-stress-induced liver function disorder response based on the in vitro experiment, while the multi-organ crosswalk mode under the thermal stress status is also essential for understanding the comprehensive mechanism of heat-stress-mediated negative effects on fish species. Full article
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27 pages, 1332 KiB  
Article
Generalizing Coherent States with the Fox H Function
by Filippo Giraldi
Quantum Rep. 2025, 7(3), 33; https://doi.org/10.3390/quantum7030033 - 28 Jul 2025
Viewed by 353
Abstract
In the present scenario, coherent states of a quantum harmonic oscillator are generalized with positive Fox H auxiliary functions. The novel generalized coherent states provide canonical coherent states and Mittag-Leffler or Wright generalized coherent states, as particular cases, and resolve the identity operator, [...] Read more.
In the present scenario, coherent states of a quantum harmonic oscillator are generalized with positive Fox H auxiliary functions. The novel generalized coherent states provide canonical coherent states and Mittag-Leffler or Wright generalized coherent states, as particular cases, and resolve the identity operator, over the Fock space, with a weight function that is the product of a Fox H function and a Wright generalized hypergeometric function. The novel generalized coherent states, or the corresponding truncated generalized coherent states, are characterized by anomalous statistics for large values of the number of excitations: the corresponding decay laws exhibit, for determined values of the involved parameters, various behaviors that depart from exponential and inverse-power-law decays, or their product. The analysis of the Mandel Q factor shows that, for small values of the label, the statistics of the number of excitations becomes super-Poissonian, or sub-Poissonian, by simply choosing sufficiently large values of one of the involved parameters. The time evolution of a generalized coherent state interacting with a thermal reservoir and the purity are analyzed. Full article
(This article belongs to the Special Issue Exclusive Feature Papers of Quantum Reports in 2024–2025)
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11 pages, 719 KiB  
Review
Killing Neck Snares Are Inhumane and Non-Selective, and Should Be Banned
by Gilbert Proulx
Animals 2025, 15(15), 2220; https://doi.org/10.3390/ani15152220 - 28 Jul 2025
Viewed by 238
Abstract
In North America, where fur trapping remains an active practice, killing neck snares continue to be used for capturing canids, particularly red fox (Vulpes vulpes), coyote (Canis latrans), and gray wolf (Canis lupus). However, over the last [...] Read more.
In North America, where fur trapping remains an active practice, killing neck snares continue to be used for capturing canids, particularly red fox (Vulpes vulpes), coyote (Canis latrans), and gray wolf (Canis lupus). However, over the last 50 years, scientific studies have consistently demonstrated that killing neck snares are inhumane—meaning that snared animals do not lose consciousness within five minutes and may remain alive for hours—and non-selective, often capturing a wide range of non-target wild and domestic animals. This non-selectivity can contribute to the local extirpation of certain species. The continued use of killing neck snares reflects a disregard for the welfare of wild mammals and poses risks to the sustainability of their populations. This persistence appears to be driven by misinformation, widespread myths, and inadequately implemented international trapping standards. These issues lead to critical questions about what must be performed to prohibit the use of these devices. Full article
(This article belongs to the Special Issue Wild Animal Welfare: Science, Ethics and Law)
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14 pages, 1343 KiB  
Article
Role of Plasma-Derived Exosomal MicroRNAs in Mediating Type 2 Diabetes Remission
by Sujing Wang, Shuxiao Shi, Xuanwei Jiang, Guangrui Yang, Deshan Wu, Kexin Li, Victor W. Zhong and Xihao Du
Nutrients 2025, 17(15), 2450; https://doi.org/10.3390/nu17152450 - 27 Jul 2025
Viewed by 405
Abstract
Objective: This study aimed to identify plasma exosomal microRNAs (miRNAs) associated with weight loss and type 2 diabetes (T2D) remission following low-calorie diet (LCD) intervention. Methods: A 6-month dietary intervention targeting T2D remission was conducted among individuals with T2D. Participants underwent a 3-month [...] Read more.
Objective: This study aimed to identify plasma exosomal microRNAs (miRNAs) associated with weight loss and type 2 diabetes (T2D) remission following low-calorie diet (LCD) intervention. Methods: A 6-month dietary intervention targeting T2D remission was conducted among individuals with T2D. Participants underwent a 3-month intensive weight loss phase consuming LCD (815–835 kcal/day) and a 3-month weight maintenance phase (N = 32). Sixteen participants were randomly selected for characterization of plasma-derived exosomal miRNA profiles at baseline, 3 months, and 6 months using small RNA sequencing. Linear mixed-effects models were used to identify differentially expressed exosomal miRNAs between responders and non-responders. Pathway enrichment analyses were conducted using target mRNAs of differentially expressed miRNAs. Logistic regression models assessed the predictive value of differentially expressed miRNAs for T2D remission. Results: Among the 16 participants, 6 achieved weight loss ≥10% and 12 achieved T2D remission. Eighteen exosomal miRNAs, including miR-92b-3p, miR-495-3p, and miR-452b-5p, were significantly associated with T2D remission and weight loss. Pathway analyses revealed enrichment in PI3K-Akt pathway, FoxO signaling pathway, and insulin receptor binding. The addition of individual miRNAs including miR-15b-3p, miR-26a-5p, and miR-3913-5p to base model improved the area under the curve values by 0.02–0.08 at 3 months and by 0.02–0.06 at 6 months for T2D remission. Conclusions: This study identified exosomal miRNAs associated with T2D remission and weight loss following LCD intervention. Several exosomal miRNAs might serve as valuable predictors of T2D remission in response to LCD intervention. Full article
(This article belongs to the Special Issue Nutrition for Patients with Diabetes and Clinical Obesity)
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34 pages, 1593 KiB  
Article
Enhancing Radial Distribution System Performance Through Optimal Allocation and Sizing of Photovoltaic and Wind Turbine Distribution Generation Units with Rüppell’s Fox Optimizer
by Yacine Bouali and Basem Alamri
Mathematics 2025, 13(15), 2399; https://doi.org/10.3390/math13152399 - 25 Jul 2025
Viewed by 210
Abstract
Renewable energy sources are being progressively incorporated into modern power grids to increase sustainability, stability, and resilience. To ensure that residential, commercial, and industrial customers have a dependable and efficient power supply, the transmission system must deliver electricity to end-users via the distribution [...] Read more.
Renewable energy sources are being progressively incorporated into modern power grids to increase sustainability, stability, and resilience. To ensure that residential, commercial, and industrial customers have a dependable and efficient power supply, the transmission system must deliver electricity to end-users via the distribution network. To improve the performance of the distribution system, this study employs distributed generator (DG) units and focuses on determining their optimal placement, sizing, and power factor. A novel metaheuristic algorithm, referred to as Rüppell’s fox optimizer (RFO), is proposed to address this optimization problem under various scenarios. In the first scenario, where the DG operates at unity power factor, it is modeled as a photovoltaic system. In the second and third scenarios, the DG is modeled as a wind turbine system with fixed and optimal power factors, respectively. The performance of the proposed RFO algorithm is benchmarked against five well-known metaheuristic techniques to validate its effectiveness and competitiveness. Simulations are conducted on the IEEE 33-bus and IEEE 69-bus radial distribution test systems to demonstrate the applicability and robustness of the proposed approach. Full article
(This article belongs to the Special Issue Mathematical Methods Applied in Power Systems, 2nd Edition)
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15 pages, 2817 KiB  
Article
Dysfunction of Autophagy in Adipose Tissue Macrophages Regulated via FoxO1 in Obesity-Related Severe Acute Pancreatitis
by Xin Ling, Zewen Zhang, Lihui Lin, Xianwen Guo and Zhen Ding
Int. J. Mol. Sci. 2025, 26(15), 7206; https://doi.org/10.3390/ijms26157206 - 25 Jul 2025
Viewed by 197
Abstract
Adipose tissue macrophages (ATMs) play important roles in the progression of obesity-related severe acute pancreatitis (SAP). This study aimed to investigate the alterations of autophagic flux within ATMs, as well as the possible regulatory mechanisms. Obese mice were induced via high-fat diets. SAP [...] Read more.
Adipose tissue macrophages (ATMs) play important roles in the progression of obesity-related severe acute pancreatitis (SAP). This study aimed to investigate the alterations of autophagic flux within ATMs, as well as the possible regulatory mechanisms. Obese mice were induced via high-fat diets. SAP was triggered using caerulein and lipopolysaccharide. Inflammatory injuries within pancreatic and adipose tissue were assessed. Autophagic flux, along with the expression of autophagosome-located soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, were examined in ATMs. RNA-sequencing was performed to identify the possible regulatory factor, which was further validated. The results showed that obesity exacerbated inflammatory injuries. ATMs in obesity-related SAP exhibited impaired autophagic flux characterized by reduced autophagosome–lysosome fusion. Expression of autophagosome-located SNARE proteins decreased in ATMs. RNA-sequencing identified Forkhead box as the differentially expressed transcription factor associated with autophagy. The expression and transcriptional activity of Forkhead box O1 (FoxO1) decreased. The inhibition of FoxO1 exacerbated SNARE proteins’ suppression and autophagic flux impairment, while the activation of FoxO1 showed the opposite effect. In conclusion, obesity-induced impaired autophagic flux and autophagosome–lysosome fusion in ATMs are potentially regulated via autophagosome-located SNARE proteins and the transcription factor FoxO1. The impaired autophagic flux in ATMs aggravated inflammatory injuries of obesity-related SAP. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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17 pages, 1873 KiB  
Article
A Novel Amdoparvovirus of Badgers and Foxes and the Perpetuation of Aleutian Mink Disease Virus 3 in the Wildlife of Denmark
by Frederikke Juncher Høeg, Anne Sofie Vedsted Hammer, Anna Cecilie Boldt Eiersted, Joost Theo Petra Verhoeven, Lars Erik Larsen, Tim Kåre Jensen and Marta Canuti
Pathogens 2025, 14(8), 734; https://doi.org/10.3390/pathogens14080734 - 25 Jul 2025
Viewed by 372
Abstract
Amdoparvoviruses, encompassing the well-characterized Aleutian mink disease viruses (AMDV) as well as less investigated viruses infecting both captive and wild animals, are important carnivoran viruses that are significant pathogens in the mink farming industry. We investigated the molecular epidemiology of amdoparvoviruses among Danish [...] Read more.
Amdoparvoviruses, encompassing the well-characterized Aleutian mink disease viruses (AMDV) as well as less investigated viruses infecting both captive and wild animals, are important carnivoran viruses that are significant pathogens in the mink farming industry. We investigated the molecular epidemiology of amdoparvoviruses among Danish wildlife. Spleen samples from 118 animals of seven carnivoran species were screened with a pan-amdoparvovirus PCR, and the identified viruses were molecularly characterized. In one of five European badgers (Meles meles), we identified an AMDV-3 strain whose ancestors were likely of farmed mink origin. This virus was last reported on a mink farm in 2002, demonstrating how farm-derived viruses have established themselves among wildlife. We also discovered and fully characterized a novel virus found in five of 81 (6.2%) foxes (Vulpes vulpes) and one of five badgers (20.0%), which we named fox and badger amdoparvovirus 1 (FBAV-1). FBAV-1 fulfills the criteria for classification as a novel species and phylogenetically is positioned as an intermediate between the North American and Eurasian amdoparvoviral clades. This study provides baseline data and expands our understanding of amdoparvoviral ecology. Further studies including more animals across diverse geographic areas are warranted to clarify amdoparvovirus epidemiology, spread, cross-species transmission, epidemic potential, and evolutionary paths. Full article
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9 pages, 1309 KiB  
Case Report
Imaging Diagnosis of Hydrocephalus in a Fox Cub-Case Study
by Alexandru Gabriel Neagu, Ruxandra Pavel, Ioana Ene, Raluca Mihaela Turbatu, Cristina Fernoaga, Niculae Tudor and Mihai Musteata
Life 2025, 15(8), 1159; https://doi.org/10.3390/life15081159 - 22 Jul 2025
Viewed by 221
Abstract
Hydrocephalus is a frequently observed congenital malformation of the central nervous system in domestic animals; however, its occurrence in wild species remains underreported. This study documents a clinical case of congenital hydrocephalus in a red fox cub (Vulpes vulpes) admitted to [...] Read more.
Hydrocephalus is a frequently observed congenital malformation of the central nervous system in domestic animals; however, its occurrence in wild species remains underreported. This study documents a clinical case of congenital hydrocephalus in a red fox cub (Vulpes vulpes) admitted to the “Visul Luanei” Wildlife Rehabilitation Center. The individual exhibited neurological deficits characterized by depressed mental status, incoordination, dromomania, behavior changes, and blindness. Diagnostic imaging, including radiography and magnetic resonance imaging (MRI), revealed a domed cranial morphology and severe dilation of the ventricular system. Notably, the lateral ventricles were markedly enlarged, with the absence of the septum pellucidum, resulting in a unified ventricular cavity. During electroencephalography (EEG) performed under general anesthesia, a high voltage and low frequency, predominantly featuring delta waves background activity was observed on all traces. Due to the poor prognosis and lack of clinical improvement, euthanasia was performed. This case contributes to the limited knowledge regarding central nervous system malformations in wild canids and underscores the need for further research on congenital neurological disorders in wildlife species. Full article
(This article belongs to the Special Issue Veterinary Pathology and Veterinary Anatomy: 3rd Edition)
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19 pages, 3009 KiB  
Article
PD-1-Positive CD8+ T Cells and PD-1-Positive FoxP3+ Cells in Tumor Microenvironment Predict Response to Neoadjuvant Chemoimmunotherapy in Gastric Cancer Patients
by Liubov A. Tashireva, Anna Yu. Kalinchuk, Elena O. Shmakova, Elisaveta A. Tsarenkova, Dmitriy M. Loos, Pavel Iamschikov, Ivan A. Patskan, Alexandra V. Avgustinovich, Sergey V. Vtorushin, Irina V. Larionova and Evgeniya S. Grigorieva
Cancers 2025, 17(14), 2407; https://doi.org/10.3390/cancers17142407 - 21 Jul 2025
Viewed by 339
Abstract
Background/Objectives: In gastric cancer, only a subset of patients benefit clinically from neoadjuvant chemoimmunotherapy, underscoring the need for robust biomarkers that can predict treatment responses and guide personalized immunotherapy. This study aimed to characterize the immune microenvironment of gastric tumors and identify predictive [...] Read more.
Background/Objectives: In gastric cancer, only a subset of patients benefit clinically from neoadjuvant chemoimmunotherapy, underscoring the need for robust biomarkers that can predict treatment responses and guide personalized immunotherapy. This study aimed to characterize the immune microenvironment of gastric tumors and identify predictive markers associated with therapeutic efficacy. Methods: We prospectively enrolled 16 patients with histologically confirmed, PD-L1–positive (CPS ≥ 1) gastric adenocarcinoma (T2–4N0–1M0). All patients received eight cycles of FLOT chemotherapy combined with pembrolizumab. Treatment response was assessed by Mandard tumor regression grading. Spatial transcriptomic profiling (10x Genomics Visium) and multiplex immunofluorescence were used to evaluate tumor-infiltrating immune cell subsets and PD-1 expression at baseline and after treatment. Results: Transcriptomic analysis differentiated the immune landscapes of responders from non-responders. Responders exhibited elevated expression of IL1B, CXCL5, HMGB1, and IFNGR2, indicative of an inflamed tumor microenvironment and type I/II interferon signaling. In contrast, non-responders demonstrated upregulation of immunosuppressive genes such as LGALS3, IDO1, and CD55, along with enrichment in oxidative phosphorylation and antigen presentation pathways. Multiplex immunofluorescence confirmed a higher density of FoxP3+ regulatory T cells in non-responders (median 5.36% vs. 2.41%; p = 0.0032). Notably, PD-1+ CD8+ T cell and PD-1+ FoxP3+ Treg frequencies were significantly elevated in non-responders, suggesting that PD-1 expression within cytotoxic and regulatory compartments may contribute to immune evasion. No substantial differences were observed in PD-L1 CPS or PD-1+ B cells and PD-1+ macrophages. Conclusions: Our findings identify PD-1+ CD8+ T cells and PD-1+ FoxP3+ Tregs as potential biomarkers of resistance to neoadjuvant chemoimmunotherapy in gastric cancer. Transcriptional programs centered on IL1B/CXCL5 and LGALS3/IDO1 define distinct immune phenotypes that may guide future combination strategies targeting both effector and suppressive arms of the tumor immune response. Full article
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14 pages, 895 KiB  
Article
Biomechanical Trade-Offs Between Speed and Agility in the Northern Brown Bandicoot
by Kaylah Del Simone, Skye F. Cameron, Christofer J. Clemente, Taylor J. M. Dick and Robbie S. Wilson
Biomechanics 2025, 5(3), 52; https://doi.org/10.3390/biomechanics5030052 - 17 Jul 2025
Viewed by 246
Abstract
Background/Objectives: Australian terrestrial mammals that fall within the critical weight range (35 g–5.5 kg) have experienced large population declines due to a combination of habitat loss and modification, and the introduction of non-native cats, dogs, and foxes. Because running speed typically increases with [...] Read more.
Background/Objectives: Australian terrestrial mammals that fall within the critical weight range (35 g–5.5 kg) have experienced large population declines due to a combination of habitat loss and modification, and the introduction of non-native cats, dogs, and foxes. Because running speed typically increases with body size, predators are usually faster but less agile than their prey due to the biomechanical trade-offs between speed and agility. Quantifying the maximum locomotor capacities of Australian mammals in the critical weight range, and the magnitude of the trade-off between speed and agility, can aid in estimating species’ vulnerability to predation. Methods: To do this, we quantified the trade-off between speed and agility in both males and females (n = 36) of a critical weight range species, the northern brown bandicoot (Isoodon macrourus), and determined if there was an influence of morphology on locomotor performance. Results: When turning, individuals who had higher turn approach speeds, and higher within-turn speeds, had greater turning radii and lower angular velocities, meaning a decrease in overall maneuverability. Females were more agile and exhibited greater turning speeds at similar turning radii than males. For both sexes, individuals with longer relative hind digits had relatively faster sprint speeds, while those with longer forearms had relatively smaller turning radii and higher agility. Conclusions: Due to the constrained limb morphology of the bandicoot species, these findings could translate across this group to provide a better understanding of their escape performance and risk of predation. Full article
(This article belongs to the Section Sports Biomechanics)
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15 pages, 4143 KiB  
Article
MET Exon 14 Skipping Mutations in Lung Cancer: Clinical–Pathological Characteristics and Immune Microenvironment
by Qianqian Xue, Yue Wang, Qiang Zheng, Ziling Huang, Yicong Lin, Yan Jin and Yuan Li
Curr. Oncol. 2025, 32(7), 403; https://doi.org/10.3390/curroncol32070403 - 14 Jul 2025
Viewed by 468
Abstract
MET exon 14 skipping mutations have emerged as significant driver alterations in non-small-cell lung cancer (NSCLC), contributing to tumor progression. This study examines the immune microenvironment in NSCLC patients with these mutations and its prognostic implications. We performed multiplex immunofluorescence (mIF) staining on [...] Read more.
MET exon 14 skipping mutations have emerged as significant driver alterations in non-small-cell lung cancer (NSCLC), contributing to tumor progression. This study examines the immune microenvironment in NSCLC patients with these mutations and its prognostic implications. We performed multiplex immunofluorescence (mIF) staining on formalin-fixed paraffin-embedded (FFPE) tissue samples from nine NSCLC patients, including four recurrent/metastatic and five non-recurrent/non-metastatic patients. Two panels assessed immune cell markers (CD8, CD4, CD20, CD68, and FoxP3) and immune checkpoints (PD-L1, LAG3, and TIM3). Immune cell infiltration and checkpoint expression were analyzed using HALOTM software (version 3.6.4134.464). Nearest neighbor analysis was conducted to assess the proximity of immune cells to tumor cells. Univariate Cox regression analysis assessed factors associated with disease-free survival (DFS). CD8+TIM3+ and CD8+LAG3+ cells were predominantly located in the tumor parenchyma of recurrent/metastatic patients but localized to the stroma in non-recurrent/non-metastatic patients. Non-recurrent/non-metastatic patients exhibited a higher density of tertiary lymphoid structures and closer proximity of CD20+ B cells, CD8+TIM3+, and CD8+LAG3+ cells to tumor cells compared to recurrent/metastatic patients, though the differences were not statistically significant. Cox regression analysis suggested a potential association between higher densities of CD8+TIM3+ cells and improved DFS (HR = 0.89), though these findings did not reach statistical significance. Our findings suggest that differences in immune microenvironmental factors, particularly those related to immune checkpoint expression (TIM3 and LAG3), may influence clinical outcomes in NSCLC patients with MET exon 14 skipping mutations. Further studies are needed to validate these observations and explore potential therapeutic implications. Full article
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17 pages, 2771 KiB  
Article
Impact of Heat Stress on Ovarian Function and circRNA Expression in Hu Sheep
by Jianwei Zou, Lili Wei, Zhihua Mo, Yishan Liang, Jun Lu, Juhong Zou, Fan Wang, Shaoqiang Wu, Hai’en He, Wenman Li, Yanna Huang and Qinyang Jiang
Animals 2025, 15(14), 2063; https://doi.org/10.3390/ani15142063 - 12 Jul 2025
Viewed by 335
Abstract
Climate change poses an increasing threat to livestock reproduction, with heat stress (HS) known to significantly impair ovarian function. This study aimed to elucidate the impact of HS on ovarian function and circRNA expression profiles in Hu sheep. Twelve ewes were randomly assigned [...] Read more.
Climate change poses an increasing threat to livestock reproduction, with heat stress (HS) known to significantly impair ovarian function. This study aimed to elucidate the impact of HS on ovarian function and circRNA expression profiles in Hu sheep. Twelve ewes were randomly assigned to a control (Con, n = 6) or HS group (n = 6) and exposed to different temperatures for 68 days. Compared with the Con group, HS significantly increased the respiratory rate (108.33 ± 3.72 vs. 63.58 ± 2.42 breaths/min), pulse rate (121.17 ± 3.98 vs. 78.08 ± 3.31 beats/min), and rectal temperature (40.17 ± 0.14 °C vs. 39.02 ± 0.21 °C; p < 0.05). Concurrently, serum antioxidant levels were markedly decreased, including total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-Px) (p < 0.05). Histological analysis revealed a significant reduction in the numbers of primordial, primary, secondary, and mature follicles, alongside an increase in antral follicles (p < 0.05). TUNEL staining demonstrated enhanced granulosa cell apoptosis (p < 0.05), accompanied by the upregulation of pro-apoptotic genes Bax and Caspase-3 and downregulation of the anti-apoptotic gene Bcl-2, as confirmed by qPCR (p < 0.05). CircRNA sequencing identified 152 differentially expressed circRNAs (120 upregulated, 32 downregulated), and enrichment analyses indicated their involvement in apoptosis, mitophagy, and the FoxO signaling pathway. Collectively, these findings demonstrate that HS impairs ovarian physiology and antioxidant defense, induces follicular damage and cell apoptosis, and alters circRNA expression profiles, providing new insights into the molecular mechanisms underlying HS-induced reproductive dysfunction in Hu sheep. Full article
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