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Background/objectives: Nasal vaccines are a promising strategy for enhancing mucosal immune responses and preventing diseases at mucosal sites by stimulating the secretion of secretory IgA, which is crucial for early pathogen neutralization. However, designing effective nasal vaccines is challenging due to the complex immunological mechanisms in the nasal mucosa, which must balance protection and tolerance against constant exposure to inhaled pathogens. The nasal route also presents unique formulation and delivery hurdles, such as the mucous layer hindering antigen penetration and immune cell access., Methods: This review focuses on cutting-edge approaches to enhance nasal vaccine delivery, particularly those targeting C-type lectin receptors (CLRs) like the mannose receptor and macrophage galactose-type lectin (MGL) receptor. It elucidates the roles of these receptors in antigen recognition and uptake by antigen-presenting cells (APCs), providing insights into optimizing vaccine delivery., Results: While a comprehensive examination of targeted glycoconjugate vaccine development is outside the scope of this study, we provide key examples of glycan-based ligands, such as lactobionic acid and mannose, which can selectively target CLRs in the nasal mucosa., Conclusions: With the rise of new viral infections, this review aims to facilitate the design of innovative vaccines and equip researchers, clinicians, and vaccine developers with the knowledge to enhance immune defenses against respiratory pathogens, ultimately protecting public health.

Phosphorylation plays a key role in Alzheimer's disease (AD) pathogenesis, impacting distinct processes such as amyloid-beta (Aβ) peptide production and tau phosphorylation. Impaired phosphorylation events contribute to senile plaques and neurofibrillary tangles' formation, two major histopathological hallmarks of AD. Blood-derived extracellular particles (bdEP) can represent a disease-related source of phosphobiomarker candidates, and hence, in this pilot study, bdEP of Control and AD cases were analyzed by a targeted phosphoproteomics approach using a high-density microarray that featured at least 1145 pan-specific and 913 phosphosite-specific antibodies. This approach, innovatively applied to bdEP, allowed the identification of 150 proteins whose expression levels and/or phosphorylation patterns were significantly altered across AD cases. Gene Ontology enrichment and Reactome pathway analysis unraveled potentially relevant molecular targets and disease-associated pathways, and protein-protein interaction networks were constructed to highlight key targets. The discriminatory value of both the total proteome and the phosphoproteome was evaluated by univariate and multivariate approaches. This pilot experiment supports that bdEP are enriched in phosphotargets relevant in an AD context, holding value as peripheral biomarker candidates for disease diagnosis.

New technologies based on virtual reality and augmented reality offer promising perspectives in an attempt to increase the assessment of human kinematics. The aim of this work was to develop a markerless 3D motion analysis capture system (MOVA3D) and to test it versus Qualisys Track Manager (QTM). A digital camera was used to capture the data, and proprietary software capable of automatically inferring the joint centers in 3D and performing the angular kinematic calculations of interest was developed for such analysis. In the experiment, 10 subjects (22 to 50 years old), 5 men and 5 women, with a body mass index between 18.5 and 29.9 kg/m 2 , performed squatting, hip flexion, and abduction movements, and both systems measured the hip abduction/adduction angle and hip flexion/extension, simultaneously. The mean value of the difference between the QTM system and the MOVA3D system for all frames for each joint angle was analyzed with Pearson's correlation coefficient (r). The MOVA3D system reached good (above 0.75) or excellent (above 0.90) correlations in 6 out of 8 variables. The average error remained below 12° in only 20 out of 24 variables analyzed. The MOVA3D system is therefore promising for use in telerehabilitation or other applications where this level of error is acceptable. Future studies should continue to validate the MOVA3D as updated versions of their software are developed.

Disruptions in the MBD5 gene have been linked with an array of clinical features such as global developmental delay, intellectual disability, autistic-like symptoms, and seizures, through unclear mechanisms. MBD5 haploinsufficiency has been associated with the disruption of primary cilium-related processes during early cortical development, and this has been reported in many neurodevelopmental disorders. In this study, we describe the clinical history of a 12-year-old child harboring a novel MBD5 rare variant and presenting psychomotor delay and seizures. To investigate the impact of MBD5 haploinsufficiency on neural primary cilia, we established a novel patient-derived cell line and used CRISPR-Cas9 technology to create an isogenic control. The patient-derived neural progenitor cells revealed a decrease in the length of primary cilia and in the total number of ciliated cells. This study paves the way to understanding the impact of MBD5 haploinsufficiency in brain development through its potential impact on neural primary cilia.

Follicular fluid (FF) is the microenvironment where a growing oocyte develops. Intrafollicular communication ensures oocyte competence and is carried out through paracrine signaling, the exchange of molecules via gap junctions, and the trafficking of extracellular vesicles (EVs). The study of FF-derived EVs is important for both translational and fundamental research in the female reproductive field. This study aimed to compare the efficacy and purity of two EV isolation methods: size-exclusion chromatography (SEC) and ultracentrifugation (UC). EVs isolated using SEC and UC were compared regarding their size and concentration using dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA); protein contamination was assessed with microBCA; specific EV markers were detected with Western blot, and EV morphology was studied with transmission electron microscopy (TEM). Our results show that although both techniques isolated small EVs, a significantly increased yield in particle number was clear with UC compared with SEC. On the other hand, SEC generated purer EVs with fewer protein contaminants and aggregates. In conclusion, the selection of the most suited approach to isolate EVs must be conducted considering the degree of recovery, purity, and downstream application of the isolated EVs.

The present study deals with the development of multifunctional biphasic calcium phosphate (BCP) scaffolds coated with biopolymers-poly(ε-caprolactone) (PCL) or poly(ester urea) (PEU)-loaded with an antibiotic drug, Rifampicin (RFP). The amounts of RFP incorporated into the PCL and PEU-coated scaffolds were 0.55 ± 0.04 and 0.45 ± 0.02 wt%, respectively. The in vitro drug release profiles in phosphate buffered saline over 6 days were characterized by a burst release within the first 8h, followed by a sustained release. The Korsmeyer-Peppas model showed that RFP release was controlled by polymer-specific non-Fickian diffusion. A faster burst release (67.33 ± 1.48%) was observed for the PCL-coated samples, in comparison to that measured (47.23 ± 0.31%) for the PEU-coated samples. The growth inhibitory activity against Escherichia coli and Staphylococcus aureus was evaluated. Although the RFP-loaded scaffolds were effective in reducing bacterial growth for both strains, their effectiveness depends on the particular bacterial strain, as well as on the type of polymer coating, since it rules the drug release behavior. The low antibacterial activity demonstrated by the BCP-PEU-RFP scaffold against E. coli could be a consequence of the lower amount of RFP that is released from this scaffold, when compared with BCP-PCL-RFP. In vitro studies showed excellent cytocompatibility, adherence, and proliferation of human mesenchymal stem cells on the BCP-PEU-RFP scaffold surface. The fabricated highly porous scaffolds that could act as an antibiotic delivery system have great potential for applications in bone regeneration and tissue engineering, while preventing bacterial infections.