Search Results (242)

Specific venom immunotherapy (VIT) in patients with hymenoptera venom allergy (HVA) represents a well-studied approach to reduce the severity of a possible anaphylactic reaction. Currently, data on mechanisms of tolerance induction at the cellular level within the first hours of therapy are lacking. To address this, total and unoccupied high-affinity IgE receptor (FcεRI) numbers per basophil, soluble FcεRI (sFcεRI) and serum tryptase levels were measured before and after the first day of VIT induction in HVA patients. Additionally, basophil activation tests (BATs) were performed at those time points. In the early phase of VIT induction, no significant change in total FcεRI receptor density on basophils was observed, but a significant increase in unoccupied FcεRI was noticeable, predominantly in patients with high total IgE and low baseline unoccupied FcεRI density. No meaningful difference in serum tryptase levels or sFcεRI levels was observed after VIT induction. BATs showed heterogeneous results, often unchanged before and after VIT (in 47% of the cases), sometimes increased (in 40%) and only rarely decreased EC₅₀ sensitivity (in 13%). Changes in the BAT EC₅₀ correlated with FcεRI receptor density changes in basophils. In summary, VIT induction led to an increased ratio of unoccupied-to-total FcεRI without notable tryptase or sFcεRI serum elevation, pointing towards subthreshold cell activation with receptor internalization and recycling. However, the mostly unchanged or even increased basophil sensitivity in EC₅₀ calls for further research to clarify the clinical relevance of these rapid receptor modulations. Full article

Skeletal muscle regeneration depends on muscle stem cells, which give rise to myoblasts that drive muscle growth, repair, and maintenance. In bats—the only mammals capable of powered flight—these processes must also sustain contractile performance under extreme mechanical and metabolic stress. However, the cellular and molecular mechanisms underlying bat muscle physiology remain largely unknown. To enable mechanistic investigation of these traits, we established the first myoblast cell lines from the pectoralis muscle of Pteronotus mesoamericanus, a highly maneuverable aerial insectivore. Using both spontaneous immortalization and exogenous hTERT/CDK4 gene overexpression, we generated two stable cell lines that retain proliferative capacity and differentiate into contractile myotubes. These cells exhibit frequent spontaneous contractions, suggesting robust functional integrity at the neuromuscular junction. In parallel, we performed transcriptomic and metabolic profiling of native pectoralis tissue in the closely related Pteronotus parnellii to define molecular programs supporting muscle specialization. Gene expression analyses revealed enriched pathways for muscle metabolism, development, and regeneration, highlighting supporting roles in tissue maintenance and repair. Consistent with this profile, the flight muscle is triglyceride-rich, which serves as an important fuel source for energetically demanding processes, including muscle contraction and cellular recovery. Integration of transcriptomic and metabolic data identified three key metabolic modules—glucose utilization, lipid handling, and nutrient signaling—that likely coordinate ATP production and support metabolic flexibility. Together, these complementary tools and datasets provide the first in vitro platform for investigating bat muscle research, enabling direct exploration of muscle regeneration, metabolic resilience, and evolutionary physiology. Full article

Nipah virus (NiV) is a highly pathogenic bat-borne zoonotic pathogen that poses a significant threat to human and animal health, with fatality rates exceeding 70% in some outbreaks. Despite its significant public health impact, there are currently no licensed vaccines or specific therapeutics available. Various virological tools—such as reverse genetics systems, replicon particles, VSV-based pseudoviruses, and recombinant Cedar virus chimeras—have been widely used to study the molecular mechanisms of NiV and to support vaccine development. Building upon these platforms, we developed a replication-competent recombinant vesicular stomatitis virus (rVSVΔG-eGFP-NiV_BD F/G) expressing NiV attachment (G) and fusion (F) glycoproteins. This recombinant virus serves as a valuable tool for investigating NiV entry mechanisms, cellular tropism, and immunogenicity. The virus was generated by replacing the VSV G protein with NiV F/G through reverse genetics, and protein incorporation was confirmed via immunofluorescence and electron microscopy. In vitro, the virus exhibited robust replication, characteristic cell tropism, and high viral titers in multiple cell lines. Neutralization assays showed that monoclonal antibodies HENV-26 and HENV-32 effectively neutralized the recombinant virus. Furthermore, immunization of golden hamsters with inactivated rVSVΔG-eGFP-NiV_BD F/G induced potent neutralizing antibody responses, demonstrating its robust immunogenicity. These findings highlight rVSVΔG-eGFP-NiV_BD F/G as an effective platform for NiV research and vaccine development. Full article

The transforming growth factor beta (TGF-$\mathsf{\beta }$) gene family is widely distributed across the animal kingdom, playing a crucial role in various cellular processes and maintaining overall health and homeostasis. The present study identified 34 TGF-$\mathsf{\beta }$ family genes based on the genome sequence in Tupaia belangeri, which were classified into the TGF-$\mathsf{\beta }$, bone morphogenetic protein (BMP), growth differentiation factor (GDF), glial cell-derived neurotrophic factor (GDNF), and Activin/Inhibin subfamilies. A phylogenetic analysis revealed the evolutionary relationships among members of the TGF-$\mathsf{\beta }$ family in T. belangeri and their homologous genes in Homo sapiens, Mus musculus, and Pan troglodytes, indicating a high degree of conservation throughout evolution. A chromosomal distribution and collinearity analysis demonstrated the localization of these genes within the genome of T. belangeri and their collinearity with genes from other species. A gene structure and motif analysis further illustrated the conservation and diversity among TGF-$\mathsf{\beta }$ family members. A protein interaction network analysis highlighted the central roles of TGFB1, TGFB3, BMP7, and BMP2 in signal transduction. A functional enrichment analysis underscored the significance of the TGF-$\mathsf{\beta }$ signaling pathway in the biological processes of T. belangeri, particularly in cell proliferation, differentiation, and apoptosis. We assessed the impact of cold acclimation treatment on the expression of TGF-$\mathsf{\beta }$ family proteins in the adipose tissue (white adipose tissue [WAT] and brown adipose tissue [BAT]) of T. belangeri using ELISA technology, finding that protein expression levels in the experimental group were significantly higher than those of in the control group. These results suggested that cold acclimation may enhance the adaptability of T. belangeri to cold environments by modulating the expression of TGF-$\mathsf{\beta }$ family genes. This study offers new insights into the role of the TGF-$\mathsf{\beta }$ family in the cold acclimation adaptation of T. belangeri, providing a scientific foundation for future genetic improvements and strategies for cold acclimation. Full article

Next to adrenergic signalling, purinergic pathways mediated by extracellular adenine nucleotides have been described to shape thermogenic and metabolic functions in brown adipose tissue (BAT). Here we describe high expression of P2X5 that is activated by ATP in mature adipocytes of BAT and differentiated brown adipocytes in vitro. The levels of other P2X family members were much lower, or expression was restricted to tissue-resident macrophages or endothelial cells. Global and brown adipocyte-specific P2rx5 deficiency resulted in lower expression of the uncoupling protein 1 (UCP1). However, indirect calorimetry studies showed that P2X5 did not affect systemic energy expenditure. Of note, glucose tolerance was impaired under chow and obesogenic high-fat diet conditions, which can be explained by lower glucose disposal into BAT but not into other organs. In summary, these data indicate a modulatory role of P2X5 in systemic and BAT-specific glucose metabolism. Full article

Glucagon-like peptide-1 (GLP-1) has emerged as a pivotal regulator in the management of glucose homeostasis, glycogen metabolism, and energy balance, positioning it as a critical therapeutic target for addressing obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). GLP-1 receptor agonists (GLP-1RAs) have shown promise for improving glycemic control and reducing weight through appetite regulation, delayed gastric emptying, and energy expenditure modulation. This narrative review explores the mechanisms of GLP-1-mediated glycogen metabolism and energy expenditure, particularly in key tissues—pancreas, liver, skeletal muscle, and adipose tissue. In the pancreas, GLP-1 enhances insulin secretion and beta-cell function. In the liver, it promotes glycogen synthesis via insulin-dependent and potential insulin-independent pathways, involving protein kinase B (AKT) and AMP-activated protein kinase (AMPK) signaling. Skeletal muscle benefits from GLP-1 through increased glucose uptake, AMPK activation, and mitochondrial function, facilitating glycogen storage. In adipose tissue, GLP-1 stimulates brown adipose tissue (BAT) thermogenesis and energy expenditure, contributing to weight loss. This increase in energy expenditure, along with enhanced glycogen metabolism, is a plausible mechanism for the weight loss observed with GLP-1RAs. Despite these advances, significant knowledge gaps remain, particularly regarding the direct hepatic effects of GLP-1, the extent to which it modulates glycogen metabolism in vivo, and its impact on thermogenesis in humans. Future research focusing on both the tissue-specific actions of GLP-1 and its systemic role in energy homeostasis and metabolic regulation will be essential for optimizing its therapeutic potential. Full article

Background/Objectives: Prostate cancer (PCa) is one of the most common cancers in men worldwide. While standard treatments often provide good initial results, many patients eventually develop resistance and experience a more aggressive relapse. Microsatellite instability (MSI) involves variations in the lengths of microsatellite base repeats in cells. Assessing the frequency of MSI is essential, as it may identify candidates for immune checkpoint inhibitors, which have shown promising outcomes. This study focuses on evaluating the MSI frequency in Mexican PCa patients and exploring its potential relationship with tumor aggressiveness. Methods: In this study, 116 formalin-fixed paraffin-embedded tumoral tissue biopsies from Mexican patients with PCa were collected from Hospital Civil de Culiacán and Pathology and Nephropathology, Diagnosis and Research Center, in the period from 2021 to 2024. The Gleason score was assessed, and the MSI was performed by multiplex PCR with a panel of five markers (NR-27, NR-21, NR-24, BAT-25, and BAT-26). High microsatellite instability (MSI-H) was defined as two or more unstable markers, low microsatellite instability (MSI-L) as an unstable marker, and microsatellite stability (MSS) as no unstable marker. Results: We found 19.83% (23/116) MSI PCa patients, of which 21.74% (5/23) were MSI-H, and 78.26% (18/23) were MSI-L. We found a major distribution of MSI-positive cases (50% (11/22)) in Gleason score 9 patients, corresponding to prognostic group 5. In addition, we found most of the instability in the BAT-26 marker in MSI PCa patients (60.87% (14/23)). Conclusions: This study is the first to evaluate the frequency of MSI in PCa within the Mexican population. Among the Mexican patients with MSI-positive PCa, there was a predominant Gleason score 9 and a majority instability of the BAT-26 marker. Full article

Bats serve as key ecological reservoirs of diverse microbial communities, including emerging viruses and antibiotic resistance genes. This study investigates the intestinal microbiota of two insectivorous bat species, Nyctalus noctula and Vespertilio murinus, at the Rostov Bat Rehabilitation Center in Southern Russia using whole metagenome shotgun sequencing. We analyzed taxonomic composition, functional pathways, antibiotic resistance genes, and virulence factors. Densoviruses, especially those closely related to Parus major densovirus, were the most dominant viral sequences identified. Metagenome-assembled densovirus genomes showed high sequence similarity with structural variations and clustered phylogenomically with viruses from mealworms and birds, reflecting both dietary origins and the potential for vertebrate infection. Functional profiling revealed microbial pathways associated with cell wall biosynthesis, energy metabolism, and biofilm formation. A total of 510 antibiotic resistance genes, representing 142 unique types, mainly efflux pumps and β-lactamases, were identified. Additionally, 870 virulence factor genes were detected, with a conserved set of iron acquisition systems and stress response regulators across all samples. These findings highlight the ecological complexity of bat-associated microbiota and viromes and suggest that synanthropic bats may contribute to the circulation of insect-associated viruses and antimicrobial resistance in urban settings. Full article

Henipaviruses are emerging zoonotic viruses that have caused deadly outbreaks in humans and livestock across several regions of the world. The fusion (F) protein of henipaviruses plays a critical role in viral entry into host cells and represents a key determinant of viral pathogenicity. This review provides a comprehensive analysis of current knowledge regarding trafficking, activation, as well as the role in particle assembly, of henipavirus F proteins. We discuss the unique characteristics of henipavirus F proteins compared to other paramyxovirus fusion proteins, with particular emphasis on their distinctive trafficking and activation mechanisms. Attention is also given to novel henipaviruses that have been detected in hosts other than bats, namely rodents and shrews. These viruses are sufficiently different that the International Committee on Taxonomy of Viruses has proposed a new genus for them, the Parahenipaviruses. We discuss how variations in F protein characteristics between Henipaviruses, Parahenipaviruses, and yet-unclassified henipa-like viruses might influence their trafficking and activation. Understanding these molecular mechanisms is crucial for developing effective therapeutic strategies against henipavirus infections and for predicting the emergence of novel henipavirus strains with pandemic potential. Full article

Purpose: This bi-centric pilot study investigates the predictive value of pre-treatment [¹⁸F]FDG PET/CT radiomics for assessing therapy response in primary mediastinal B-cell lymphoma (PMBCL). Methods: All PMBCL patients underwent PET/CT with [¹⁸F]FDG between January 2011 and January 2022 at Policlinico Tor Vergata University Hospital of Rome (70% training and 30% internal validation cohort) and Sant’Anna University Hospital of Ferrara (external validation cohort). The Deauville score (DS) was used as a predictor of therapy response (DS1-DS3 vs. DS4/DS5). A total of 121 quantitative radiomics features (RFts) were extracted from manually segmented volumes of interest (VOIs) in PET and CT images, according to IBSI. ComBat harmonization was applied to correct the center variability of features, followed by class balancing with SMOTE. Two machine learning (ML) prediction models, the PET model and the CT model, were independently developed using robust RFts. For each ML model, two different algorithms were trained (i.e., Random Forest, RF, and Support Vector Machine, SVM) using 10-fold cross validation, tested on the internal/external validation set. Receiver operating characteristic (ROC) curves, area under the curve (AUC), classification accuracy (CA), precision (Prec), sensitivity (Sen), specificity (Spec), true positive (TP) scores, and true negative (TN) scores were computed. Results: The entire dataset was composed of 29 samples for the Rome cohort (23 from D1–D3 and 6 from D4/D5) and 9 samples for the Ferrara cohort (4 from D1–D3 and 5 from D4/D5). A total of 27 RFts were identified as robust for each imaging modality. Both the CT and PET models effectively predicted the Deauville score. The performance metrics of the best classifier (SVM) for the CT and PET models in external validation were AUC = 0.75/0.80, CA = 0.85/0.77, Prec = 0.97/0.67, Sen = 0.60/0.80, Spec = 0.98/0.75, TP = 75.0%/66.7%, and TN = 77.8%/85.7%, respectively. Conclusions: ML models trained on [¹⁸F]FDG PET/CT radiomic features in PMBLC patients could predict the Deauville score. Full article

The increasing integration of renewable energy into modern power systems has prompted the need for efficient hybrid energy solutions to ensure reliability, sustainability, and economic viability. However, optimizing the design of hybrid renewable energy systems, particularly those incorporating both hydrogen and battery storage, remains challenging due to system complexity and fluctuating energy trading conditions. This study addresses these gaps by proposing a novel framework that combines the Chimp Optimization Algorithm (ChOA) with a rule-based energy management strategy (REMS) to optimize component sizing and operational efficiency in a grid-connected microgrid. The proposed system integrates photovoltaic (PV) panels, wind turbines (WT), electrolyzers (ELZ), hydrogen storage, fuel cells (FC), and battery storage (BAT), while accounting for seasonal variations and dynamic energy trading. Each contribution in the Research Contributions section directly addresses critical limitations in previous studies, including the lack of advanced metaheuristic optimization, underutilization of hydrogen-battery synergy, and the absence of practical control strategies for energy management. Simulation results show that the proposed ChOA-based model achieves the most cost-effective and efficient configuration, with a PV capacity of 1360 kW, WT capacity of 462 kW, 164 kWh of BAT storage, 138 $H_2$ tanks, a 571 kW ELZ, and a 381 kW FC. This configuration yields the lowest cost of energy (COE) at $0.272/kWh and an annualized system cost (ASC) of $544,422. Comparatively, the Genetic Algorithm (GA), Salp Swarm Algorithm (SSA), and Grey Wolf Optimizer (GWO) produce slightly higher COE values of $0.274, $0.275, and $0.276 per kWh, respectively. These findings highlight the superior performance of ChOA in optimizing hybrid energy systems and offer a scalable, adaptable framework to support future renewable energy deployment and smart grid development. Full article

Background: Whether intestinal epithelial cells can regulate distant adipose tissue remains a mystery. Methods: Cold-stimulated intestinal epithelial cell-derived exosomes (Cold IEC-Exo) play a pivotal role in enhancing adipose thermogenesis and metabolic homeostasis, as demonstrated in this study. Results: IEC-Exo can accumulate in adipose tissue. Compared with IEC-Exo derived from room temperature mice (RT IEC-Exo), Cold IEC-Exo significantly enhanced the thermogenesis of adipose. In vitro, Cold IEC-Exo directly stimulated thermogenesis in primary adipocytes by elevating oxygen consumption rate, proton leak, and fatty acid uptake, with no effect on glucose uptake. Small RNA sequencing identified miR-674-3p as a key mediator enriched in Cold IEC-Exo. miR-674-3p mimicry replicated Cold IEC-Exo effects, augmenting Ucp1 expression, mitochondrial uncoupling, and fatty acid utilization in adipocytes. Local overexpression of miR-674-3p in BAT and sWAT via AAV in vivo enhanced thermogenesis and attenuated diet-induced glucose intolerance. Conclusions: These findings establish that Cold IEC-Exo, via miR-674-3p transfer, drive adipose thermogenic activation and mitigate metabolic dysfunction, highlighting their therapeutic potential in obesity-related disorders. Full article

Adipose tissue exhibits remarkable plasticity in adapting to thermal stress, yet the epigenetic mechanisms coordinating metabolic reprogramming in large mammals—particularly in livestock species lacking classical brown adipose tissue (BAT) such as swine—remain elusive. Using a porcine cold exposure model, we investigated adipose adaptation mechanisms through integrated single-cell RNA sequencing and bulk transcriptomic analyses of subcutaneous adipose tissue (subWAT). We identified a cold-induced thermogenic adipocyte subpopulation, characterized by upregulated DHRS4 expression. Mechanistically, cold exposure induced hypomethylation at the DHRS4 promoter locus, enhancing its expression to potentiate fatty acid β-oxidation, accompanied by thermogenic capacity upregulation. Our findings establish DHRS4 as an epigenetic–metabolic switch governing cold adaptation and a potential target for improving cold resistance in swine production systems. Full article

Cedar virus (CedV), closely related to the Hendra and Nipah viruses, is a novel Henipavirus that was originally isolated from flying foxes in Australia in 2012. Although its glycoprotein G exhibits relatively low sequence similarity with its counterparts of the Hendra and Nipah viruses, CedV also uses ephrin receptors, i.e., ephrins B1, B2, A2 and A5, to enters human cells. Nevertheless, the entry mechanism of CedV into bat cells remains unexplored. Considering that Rousettus aegyptiacus (Egyptian Rousette bat, ERB) is postulated to be a reservoir host for henipaviruses, we aim to reveal the receptors utilized by CedV to enable its entry into ERB cells. To this end, we cloned the class A and B ephrins of ERB and generated CHO-K1 cells stably expressing individual ephrins. We also developed a lentivirus-based pseudovirus system containing the firefly luciferase reporter. Assessment of the luciferase activity in cells expressing single ephrins demonstrated that the ERB ephrin B1 and B2 mediated CedV pseudovirus entry. Further, we generated a recombinant CedV expressing the fluorescent protein TurboFP635 (rCedV-nTurbo635). By performing high-content microscopy and flow cytometry, we unveiled that, in addition to ephrin B1 and B2, ephrin A5 was also able to mediate rCedV-nTurbo635 entry, although to a much lesser extent. In contrast to human ephrin A2, ERB ephrin A2 failed to mediate rCedV-nTurbo635 entry. Finally, we generated ERB epithelial cells with ephrin B1 and/or ephrin B2 knockdown (KD). The entry of rCedV-nTurbo635 into ERB epithelial cells was drastically impaired by ephrin B1/B2 KD, validating the importance of ephrin B1 and B2 in its entry. Altogether, we conclude that CedV primarily employs ERB ephrin B1, B2 and, possibly, A5 for its entry into ERB cells. Full article

As a significant zoonotic disease, rabies poses substantial economic challenges for the livestock sector, highlighting the need for effective wildlife monitoring as part of a One Health approach. This study documents the first case of paralytic rabies in a lowland tapir (Tapirus terrestris) at the Guaycolec Wildlife Station in Formosa, Argentina. The 12-year-old male tapir exhibited neurological symptoms, including limb paralysis and dysphagia, leading to its death. The rabies virus was confirmed through direct immunofluorescence, virus isolation in BHK-21 cells, and molecular diagnostics via real-time RT-PCR and conventional PCR. Antigenic variant 3, associated with Desmodus rotundus, was identified. Histopathological examination revealed non-suppurative encephalitis with lymphocytic perivascular cuffs, neuronal vacuolization, and acidophilic intracytoplasmic inclusion bodies in the grey matter. This case underscores the importance of expanded surveillance for non-traditional hosts, as it demonstrates the potential for rabies transmission in changing environments. The findings highlight the need to maintain epidemiological surveillance systems at the wildlife–livestock–human interface and to develop targeted control strategies to mitigate the spread of rabies, particularly in areas where vampire bat populations are subject to anthropogenic pressures. Comprehensive monitoring and early detection are essential for effective rabies management in both wildlife and urban contexts. Full article