Multidisciplinary Digital Publishing Institute (Switzerland)
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Constitutively Active Stat5b Expression in Dendritic Cells Enhances Treg-Mediated Elimination of Autoreactive CD8+ T Cells in Autoimmune Diabetes
No full textIn type 1 diabetes (T1D) in non-obese diabetic (NOD) mice, dendritic cells (DCs) exhibit a Stat5b mutation that impairs regulatory T cell (Tregs) numbers and suppressive function. To correct this defect, we generated transgenic NOD mice expressing constitutively active Stat5b (NOD.Stat5b-CA) in DCs, which conferred protection from diabetes that was associated with an expanded Treg population and a marked reduction in CD8+ T cell frequencies in secondary lymphoid organs. However, the phenotypic characteristics and underlying mechanisms to eliminate CD8+ T cells in NOD.Stat5b-CA mice are unknown. In this study, we found that the frequency of Tregs was significantly higher in the thymus and peripheral lymphoid organs of NOD.Stat5b-CA mice compared with NOD mice. Tregs in the peripheral lymphoid organs exhibited increased expression of activation markers CD69 and OX40, alongside reduced CD62L. We also found that CD8+ T cell frequencies were reduced in the peripheral organs but not in the thymus of NOD.Stat5b-CA mice, while CD4+ T cell frequencies remained unchanged across all organs. Furthermore, NOD.Stat5b-CA mice exhibited a reduced frequency of central Tregs (CD62Lhigh CD44low) and increased frequency of effector Tregs (CD62Llow CD44high) under steady-state conditions compared to NOD mice. Notably, Tregs from NOD.Stat5b-CA mice displayed enhanced cytotoxic activity, evidenced by increased expression of perforin, granzyme B, and Fas ligand, potentially mediating CD8+ T cell frequency reduction. Collectively, these findings highlight a novel role for Stat5b-CA.DC-educated Tregs in modulating immune responses by eliminating peripheral pathogenic CD8+ T cells via cytotoxic pathways, thereby contributing to immune regulation in NOD.Stat5b-CA mice
A Stepwise Integrative Approach to Managing a Refractory Recurrent Cervical Sialocele in a Dog
No full textRecurrent canine cervical sialocele is most often caused by incomplete excision of the mandibular–sublingual gland complex, leading to anatomical distortion and concealment of residual tissue. This case describes the multimodal management of a repeatedly recurrent cervical sialocele in a young, small-breed dog following multiple previous revision surgeries. A stepwise bridging strategy was adopted before definitive salvage surgery. Oral phenobarbital was instituted, resulting in partial reduction in fluid accumulation and improved comfort. Ultrasound-guided intracavitary sclerotherapy with OK-432 was then performed, inducing a localized fibrotic response but without durable cure. Final resolution was achieved only after salvage ventral paramedian (VPM) sialoadenectomy, which provided wide exposure for complete excision of deeply concealed sublingual remnant tissue within a fibrotic pseudocapsule. Histology confirmed a cervical sialocele. Transient neuropraxia resolved within 3 weeks, and no recurrence was observed at 6 months postoperatively. To the authors’ knowledge, this is the first report describing intracavitary OK-432 sclerotherapy as part of a staged multimodal strategy for canine cervical sialocele. This case illustrates the feasibility of integrating medical salivary suppression and minimally invasive sclerotherapy as bridging measures before salvage VPM surgery for refractory cervical sialocele
SARS-CoV-2 Helicase (NSP13) Interacts with Mammalian Polyamine and HSP Partners in Promoting Viral Replication
No full textWe present a computational study that precedes the potential interactions between SARS-CoV-2 helicase (NSP13) and selected host proteins implicated in chaperone-assisted folding and polyamine metabolism. Using structure-based modelling and protein–protein docking (BioLuminate v4.6), followed by all-atom molecular dynamics (MD) simulations (GROMACS v2018.6), and comparative MM-GBSA scoring (HawkDock v2), we evaluated the stability and interface properties of NSP13 complexes with cytosolic heat shock proteins; heat shock protein 40 (HSP40), heat shock protein 70 (HSP70), heat shock protein 90 (HSP90) and the polyamine biosynthesis enzyme ornithine decarboxylase (ODC). Docking, MD, and interface analyses indicate distinct complex behaviours: HSP70-NSP13 complexes sampled compact conformations, HSP90-NSP13 ensembles displayed greater conformational heterogeneity but more favourable comparative MM-GBSA estimates, and ODC-NSP13 interfaces were comparatively well packed. Per-residue contact mapping identified a small set of recurrent NSP13 residues, Lys22 and Asn51, as putative interaction hotspots. The reported findings herein generate testable hypotheses about NSP13 recruitment of host chaperones and modulation of polyamine metabolism that may inform downstream experimental studies
Real-Time Monitoring of Microbial Contamination and Stress Biomarkers with Liquid Crystal-Based Immunosensors for Food Safety Assessment
No full textAquaculture is a crucial global food production sector that faces challenges in water quality management, food safety, and stress-related health concerns in aquatic species. Cortisol, a key stress biomarker in fish, and Escherichia coli (E. coli) contamination in bivalve mollusks are critical indicators that require sensitive and real-time detection methods. Liquid crystal (LC)-based immunosensors have emerged as a promising solution for detecting biological analytes due to their high sensitivity, rapid response, and label-free optical detection capabilities. Therefore, this study explores the development and application of LC-based immunosensors for the detection of cortisol in artificial and real recirculating aquaculture system (RAS) samples, as well as E. coli in real contaminated water and clam samples during the depuration processes of bivalve mollusks. The biosensors exhibited the capacity to detect cortisol with a response time in seconds and a limit of detection (LOD) of 0.1 ng/mL. Furthermore, they demonstrated specificity to cortisol when tested against different interfering substances, including testosterone, glucose, and cholesterol. Furthermore, it was possible to correlate cortisol concentrations in different filtration stages and track E. coli contamination during depuration. The results confirm the feasibility of LC-based immunosensors as a user-friendly, portable, and efficient diagnostic tool for aquaculture applications
Assessment of Solid Biomass Combustion in Natural Fiber Packages
No full textUrban tree-management operations generate substantial amounts of woody biomass that often remain underutilized despite their potential value as a local renewable fuel. This study investigates the possibility of using woodchips and sawdust delivered from municipal tree-cutting activities as boiler fuel, with a specific focus on how fuel moisture, particle size, and natural-fiber packaging influence combustion performance and emission characteristics. In collaboration with a municipal greenery-cutting company, representative batches of biomass were collected, characterized through proximate and ultimate analyses, and combusted in a small-scale boiler. Unlike conventional densification routes (pelletization/briquetting), the proposed approach uses combustible natural-fiber packaging to create modular ‘macro-pellets’ from minimally processed urban residues. The study quantifies how this low-energy packaging concept affects emissions and boiler efficiency relative to loose chips/sawdust at two moisture levels. The results demonstrate that packaging the fuel in jute bags markedly improved performance for both woodchips and sawdust by stabilizing the fuel bed, enhancing air distribution, and reducing emissions of incomplete combustion products. Boiler efficiency increased from approximately 60% for raw unpackaged fuels to 71–75% for the dried and jute-packaged variants. The findings highlight that simple preprocessing steps—drying and packaging in natural-fiber bags—can substantially enhance the energy recovery potential of urban green waste, offering a practical pathway for integrating municipal biomass residues into a sustainable fuel
Small-Sample Thermal Fault Diagnosis Using Knowledge Graph and Generative Adversarial Networks
No full textThe scarcity of fault samples significantly impedes the generalization of data-driven diagnosis models for local thermal imbalances in integrated energy systems. To overcome this limitation, this paper proposes a novel knowledge graph-guided conditional generative adversarial network (KG-GAN) framework. The approach begins by constructing a dynamically updatable fault knowledge graph for district heating systems, which explicitly encapsulates pipeline topology, thermodynamic principles, and fault propagation mechanisms. The derived knowledge embeddings are then fused with physics-based constraints into the adversarial learning process, effectively alleviating the issue of physically implausible sample generation that plagues conventional data-centric models. Experimental validation on a district heating platform, involving four common fault types, demonstrates the superiority of our method. With only 100 samples per fault category, a diagnostic model trained on KG-GAN-generated data achieves a classification accuracy of 91.7%, outperforming a GAN-based baseline by 8.3%. Furthermore, t-Distributed Stochastic Neighbor Embedding (t-SNE) visualization reveals a 92.3% feature distribution consistency between generated and real samples, confirming the method’s capability to enhance diagnostic robustness and physical interpretability under small-sample conditions
Is Obesity a Modifiable Risk Factor in Multiple Sclerosis? Mechanistic Insights into Neuroinflammation and Oxidative Damage
No full textIntroduction: Multiple sclerosis (MS) is a chronic autoimmune inflammatory disorder of the central nervous system (CNS) that leads to demyelination of CNS neurons and is influenced by genetic, environmental, and lifestyle factors, including diet and obesity. Methods: This review aims to analyze at the molecular level the relationship between obesity, as a chronic inflammatory condition, and the pathophysiology of MS, as a chronic autoimmune inflammatory disease, in order to understand the complex links between obesity and MS through a search of the PubMed and Google Scholar databases. Discussion: Chronic inflammation and OS are interconnected processes, causing a toxic state, which contributes to the development of CNS neuroinflammation and neuronal damage, resulting in neuronal demyelination and the onset of MS. Adipose tissue is a complex endocrine organ; in addition to being a lipid storage organ, it secretes cytokines and adipokines, which are involved in the regulation of hormones, metabolism, inflammation, and whole-body homeostasis. Obesity triggers chronic low-grade inflammation, disruption of the blood–brain barrier (BBB) and brain metabolism, infiltration of the CNS by immune cells, production of ROS, and generation of oxidative stress (OS). Anti-inflammatory and pro-inflammatory adipokines are also implicated in MS and obesity. Conclusions: Obesity affects MS through common underlying mechanisms and seems to be a modifiable risk factor. Antioxidant and anti-inflammatory compounds with multi-functional characteristics could be additional tools to slow the progression of MS and its promotion through obesity while also offering potential treatment options for both conditions via their multi-targeting characteristics
Geometric Morphometric Analysis of Hard and Soft Tissue in Class III Malocclusion Before and Near-End Orthodontic Treatment
No full textBackground/Objectives: Geometric morphometric analysis (GMA) is a statistical method that captures and quantifies shape variation. This study aimed to assess hard and soft tissue shape variations and changes following orthodontic treatment in Class III skeletal malocclusion using GMA. Methods: A retrospective study was conducted on 84 lateral cephalometric radiographs (pre-treatment and near-end treatment) of Class III patients aged 16–40 years (ANB < 2°). Thirty-five landmarks were digitized in Cartesian coordinates using MorphoJ software for shape analysis. Results: The sample included 62% females and 38% males, with a mean age of 24.7 ± 5.2 years. Vertical dimension variations (hypodivergent to hyperdivergent) contributed most to shape changes PC1 (23.35%), followed by anteroposterior variations PC2 (13.51%). Gender significantly influenced hard and soft tissue variation with 30.91%SS (F = 56.99, p < 0.0001). Males had significantly larger and longer ramus, body of the mandible, alveolar height, LAFH, TAFH and upper lip length. (PD: 0.026, p < 0.05). Significant shape changes were seen in the mandible (PD = 0.018, p < 0.05). SNB increased by 0.41° (from 81.73° ± 3.67°), and ANB improved by 0.46° but remained Class III (−0.33° ± 1.82°). Lower anterior facial height increased by 1.78 mm (p < 0.05). The lower incisors retroclined significantly (from 92° ± 8.56° to 87° ± 6.96°, p < 0.05), while the interincisal angle increased by 5.9°. Upper incisors remained procline (118° ± 11°, p > 0.05). Upper lip length increased by 0.4 mm (p < 0.05). Conclusions: Vertical and anteroposterior shape variations are notable within Class III malocclusion. Post-treatment changes in both hard and soft tissues indicate that orthodontic camouflage can enhance facial esthetics and skeletal balance. GMA provides objective quantification and visualization of these treatment-related craniofacial changes
Serotonergic Signaling Rewired: A Lipid Raft-Controlled Model of Synaptic Transmission Grounded in the Fundamental Parameters of Biological Systems
No full textSerotonergic signaling is traditionally conceived as a transient, vesicle-mediated process restricted to the synaptic cleft. Here, we propose an expanded model in which serotonin can also be inserted into the plasma membrane of neurons and glial cells, forming a stable, membrane-associated reservoir that prolongs its availability beyond classical synaptic timescales. In this framework, the synapse emerges not as a simple neurotransmitter–receptor interface but as a dynamic, multiscale medium where membrane order, hydration, and quantum-level processes jointly govern information flow. Two temporal “tunnels” appear to regulate serotonin bioavailability: its aggregation in synaptic vesicles during exocytosis, and its cholesterol-dependent insertion into neuronal and glial membranes at the tripartite synapse. Lipid raft microdomains enriched in cholesterol and gangliosides thus act as active regulators of a continuum between transient and constitutive serotonin signaling. This extended serotonergic persistence prompts a reconsideration of current pharmacological models and the action of antidepressants such as fluoxetine, which not only inhibits the serotonin transporter (SERT) but also accumulates in lipid rafts, perturbs raft organization, and alters serotonin–cholesterol equilibria, contributing to SERT-independent effects. Grounded in the recently established fundamental parameters of biological systems, this model invites a broader, quantum-informed rethinking of synaptic transmission
