Abstract: Gibson’s concept of optic flow established that perception is grounded in lawful, action-generated structure rather than in discrete sensory signals. While optic flow specifies self-motion visually, no corresponding framework has been formally established for the mechanical and kinesthetic information generated during skilled action. This study introduces haptic flow as a screw-structured, symmetry-bearing invariant that specifies kinesthetic information in human movement. Using screw theory, we model haptic flow as the continuous evolution of instantaneous screw axes and pitch, capturing the coupled rotational–translational dynamics of the body–object system. This framework is applied to the golf swing as a paradigmatic case of skilled manipulation. Motion data from proficient and novice performers reveal clear geometric differences: proficient performance is characterized by coherent alignment between instantaneous screw axes and the club’s principal inertia axis, stabilization of pitch through impact, and the emergence of harmonic screws lying on a common cylindroid. In contrast, novice performance exhibits fragmented screw organization, elevated pitch variability, and pronounced geometric asymmetry. These results demonstrate that skilled manipulation is structured by a continuous, internally generated flow of mechanical information that is invariant across critical phases of action. Interpreted in Gibsonian terms, harmonic screws function as perceivable affordances—symmetry-stabilized modes that couple inertia and potential and guide action without reliance on explicit feedback or internal models. The proposed concept of haptic flow thus extends ecological perception–action theory into the mechanical domain and provides a quantitative symmetry-based framework for analyzing skilled human movement.

Abstract: Background: Healthcare professionals experience continuous biological and psychosocial stressors that may disturb oral and systemic homeostasis. Alterations in salivary secre-tion, mucosal immunity, and microbiome composition reflect adaptive cellular responses to chronic occupational stress. Understanding these mechanisms may provide a biologi-cal framework for resilience and wellbeing in clinical everyday practice. Objective: To narratively review the evidence linking oral cellular and molecular mechanisms, -salivary biomarkers, epithelial and immune cell activity, and microbiome dynamics- with stress, fatigue, burnout, and wellbeing outcomes among healthcare professionals. Methods: A PRISMA-guided search of PubMed, Scopus, Web of Science, and Cochrane Oral Health identified studies investigating oral cellular or molecular parameters in relation to occu-pational stress or wellbeing indicators in healthcare settings. Eligible designs included observational, experimental, and interventional studies. Data were extracted using stand-ardized forms, quality was appraised via ROBINS-I and the Newcastle-Ottawa scale, and results were synthesized thematically. Results: Evidence from 99 studies suggests that chronic occupational stress elevates salivary cortisol, oxidative stress markers, and pro-inflammatory cytokines (IL-6, TNF-α), while reducing protective salivary immuno-globulin A and microbiome diversity. Balanced oral immune and microbial profiles were associated with better psychological adaptation and lower fatigue indices. Conclusions: Oral cellular homeostasis offers a promising window into the biological underpinnings of occupational stress and resilience in healthcare professionals. Systematic integration of salivary and mucosal biomarkers into workplace wellbeing programs could enhance ear-ly detection of dysregulated stress physiology. Future interdisciplinary research should bridge oral biology, occupational medicine, and mental health to strengthen sustainable wellbeing strategies across the health workforce.

Abstract: The global health crisis driven by Antimicrobial Resistance (AMR) necessitates an urgent pivot toward novel therapeutic agents, with traditional medicinal plants serving as a critical resource. The Asteraceae genus Verbesina, particularly utilized in Mexican ethnobotany, has garnered scientific attention due to its potent bioactive profile against infection and inflammation. This review provides a comprehensive and critical synthesis of the pharmacological landscape of Verbesina species, focusing specifically on the dual role of its major secondary metabolites, the Sesquiterpene Lactones (SLs), as both cytotoxic and antimicrobial agents. We systematically compile and analyze reported in vitro data, including IC50 values from cancer and non-cancerous cell lines, and MIC values against clinically relevant drug-resistant strains like S. aureus and E. coli. A core focus is placed on establishing the therapeutic index (SI = IC50/MIC) for lead compounds, providing a crucial indicator of drug feasibility. Furthermore, we review the proposed molecular mechanisms of SL action, such as the crucial role of the α-methylene-γ-lactone moiety in alkylating cellular targets, which underpins both their antiproliferative and bactericidal effects. By critically bridging ethnopharmacology with modern mechanistic data, this review validates the translational potential of Verbesina metabolites and highlights clear directions for bioassay-guided isolation and optimization as next-generation anti-resistance scaffolds.

Abstract: The process of developing a drug is complex and involves many steps, from basic research (bench) to patient applications (bedside), which are conducted to ensure the drug is both safe and effective. In cancer research, the failure rate is high when translating basic findings to clinical trials. One of the main factors probably contributing to high failure rates is the basic quality of in vitro and in vivo study designs. Advanced basic cancer research techniques, including various types of 3D cell culture, the use of valuable organoids, organs, or tumors on chips, traditional or automated Western blots, omics research, advanced imaging techniques, usage of cutting-edge preclinical models and others, may produce inaccurate results for translational research if the basic study design is not carefully planned, especially when drugs or compounds are involved. In this manuscript, the author discussed (i) the importance of understanding and applying pharmacokinetic data in basic research, (ii) a proper comparison of the efficacy and safety of investigational drugs with the standard of care, (iii) the importance of following the actual route of drug administration as experienced by patients, the cruciality of human-to-animal dose conversion, and dose frequencies in animal models, (iv) significance of the age, gender, and strain of mice, along with adherence to the ARRIVE guidelines for ensuring transparency in conducting and reporting preclinical research, (v) benefits of having both subcutaneous and metastasis models in preclinical studies, (vi) the impact of comorbidities and related cancer drug studies in animal models and (vii) the importance of testing drug candidate/s in model mimicking acidic tumor microenvironment.

Abstract: Background/Objectives: Upper respiratory tract infections (URTIs) and exercise-induced immune perturbations are common in adults and may adversely affect quality of life, productivity, and physical performance. Immunoglobulin Y (IgY), a food-derived antibody with broad antimicrobial activity, has demonstrated immunomodulatory potential in preclinical and limited clinical studies. This study evaluated the effects of a multi-pathogen-specific IgY supplement (Muno-IgY) on respiratory health, immune and inflammatory markers, exercise-induced physiological stress, and gut microbiome composition in healthy adults. Methods: in this 12-week, double-blind, placebo-controlled trial, 28 healthy adults with a history of URTI were randomly allocated to receive Muno-IgY or placebo. URTI incidence, duration, and severity were recorded daily. Serum immune and inflammatory biomarkers were assessed longitudinally and in response to a standardized exercise challenge. Gut microbiome composition was analyzed using shotgun metagenomic sequencing at baseline and week 12. Safety and tolerability were assessed throughout the study. Results: URTI incidence was numerically lower in the Muno-IgY group compared with placebo (14.3% vs. 35.7%), with shorter average duration and fewer missed workdays (p > 0.05). Following an acute exercise challenge, Muno-IgY supplementation resulted in a significant increase in serum IgA at 24 h post-exercise (p = 0.022) and a significantly greater reduction in lactate dehydrogenase at 1 h post-exercise compared with placebo (p < 0.0001). Exploratory gut microbiome analyses revealed favorable directional shifts in microbial composition. Conclusions: In this exploratory pilot study, Muno-IgY supplementation was safe and associated with significant improvements in selected markers of exercise-induced immune response and muscle damage, alongside favourable trends in respiratory health and gut microbiome composition. These findings support further evaluation of Muno-IgY in larger, adequately powered clinical trials.

Abstract: Background/Objectives: Neurodegenerative diseases (NDs) have a severe impact on patients’ quality of life, and effective treatments remain limited. As the focus is treating the symptoms, the root cause of the problem e commonly not addressed. Stem cells show an emerging potential due to the ability for self-renew combined with their ca-pability for differentiation into various cell lines, which makes them a strong candidate to regenerative therapies in general, and for application in neurological issues in par-ticular. This article provides an overview on the safety, efficacy and challenges associ-ated with the use of mesenchymal stem cells (MSCs), their derived secre-tome/exosomes and their combination with biomaterials in clinical and preclinical models of Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). Methods: A systematic search was conducted on PubMed, Web of Science and Scopus to identify published studies providing clinical and preclinical evidence on the use of MSCs in neurodegenerative disorders. Results: Overall, the literature consistently indicates that MSCs and their derivatives exert disease-modifying effects across multiple NDs. Across AD, PD, HD and ALS, preclinical studies uniformly report improvements in behavioural outcomes, attenuation of neuroinflammation, and neuroprotective effects, largely mediated by MSC paracrine signalling rather than direct cell replacement. Clinical studies to date consistently support the safety and feasibility of MSC-based therapies, while efficacy signals remain modest, heterogeneous and predominantly short-term, highlighting the need for larger, well-controlled trials. Conclusions: Inte-gration of genetic engineering, preconditioning, and EV technology may represent a paradigm shift in neuroregeneration, offering a scalable and minimally invasive fron-tier to improve long-term clinical outcomes in patients with AD, PD, HD, and ALS.

Abstract: Armed conflicts disrupt healthcare systems, creating profound challenges for children with congenital heart disease (CHD). Time is a critical determinant of cardiac physiology, disease progression, and surgical feasibility. This editorial highlights how delays in diagnosis and treatment transform otherwise reversible conditions into advanced, irreversible, and life-limiting disease. Focusing on pulmonary vascular disease in neglected shunt lesions, truncus arteriosus, and left ventricular (LV) deconditioning in D-transposition of the great arteries (D-TGA), we outline the pathophysiological pathways through which delayed intervention limits therapeutic options. We also emphasize the ethical responsibility of the global pediatric cardiology community to develop wartime-resilient care models.

Abstract: Diabetes Mellitus (DM) favors kidney remodeling, leading to diabetic kidney disease (DKD). Kidney histological alterations are identified after DKD installation, but have not been studied in the early stage of DM. We studied renal remodeling in Wistar rats at the early stage of DM, before DKD development, investigating alterations indicating a poor prognosis and whether age is an impact factor. Diabetes was induced with Alloxan. Groups: adult diabetic (DMA), elderly diabetic (DMI), adult sham control (CSA), and elderly sham control (CSI). After 30 days of confirmed diabetes, blood, urine, and kidney were collected. Both diabetic groups presented normal renal function. DMA and DMI showed tubular infiltration and hypertrophy, decreased Bowman's space, and reduced glomerular area. A decrease in the glomeruli number was observed in the DMI. An inverse correlation between the glomeruli number and the ApoB/ApoA ratio was observed on DMA. We conclude that histological changes characteristic of DKD can be observed in the early stages of DM, and age can have a role in the injury intensity. Tubular and glomerular alterations occur during DM installation and continue to evolve as DKD develops. Therefore, targeting the prevention of kidney remodeling could be a good therapeutic approach to prevent DKD.

Abstract: Ocular diseases – including glaucoma, diabetic retinopathy, and age-related macular degeneration – remain major global causes of irreversible vision loss. Despite therapeutic advances, current interventions that address the convergent metabolic, inflammatory, vascular and neurodegenerative components of these diseases are limited. Glucagon‑like peptide‑1 receptor agonists (GLP‑1RAs), widely used for type 2 diabetes and obesity, have emerged as multi-target candidates for ocular therapeutics due to their pleiotropic anti‑inflammatory, antioxidant, vasculoprotective, and neuroprotective properties. Increasing preclinical and clinical evidence indicates that GLP‑1RAs preserve blood–retina barrier integrity, inhibit pathological angiogenesis, reduce inflammation, promote antioxidant responses and protect retinal neurons from degeneration. However, rare ocular adverse events – including nonarteritic anterior ischemic optic neuropathy and “early worsening” of diabetic retinopathy – highlight the need for a balanced and comprehensive consideration of evidence. This review synthesizes mechanistic in-sights, experimental findings, clinical data, and safety considerations to critically assess the potential of GLP‑1RAs as disease‑modifying therapeutics for ocular disorders and outlines translational challenges and research priorities to guide future ophthalmology‑focused investigations.

Abstract: The presence of heavy metal in the sediments of tropical rivers is a significant hazard to the ecological quality and human health; however, the relationships of the biomagnification of metals have not been sufficiently investigated in urban West African environments. The current study determined the bioavailability and ecological risk of eight heavy metals (As, Cd, Cr, Fe, Mn, Ni, Pb, Se) in Nworie and Otamiri Rivers sediments, Nigeria. The BCR sequential extraction procedure was used to determine concentrations and distribution among four fractions (F1 -F4 ). The Risk Characterization used the Risk Ranking Index (RAC), the Geo-accumulation Index (Igeo), and the Potential Ecological Risk Index (PERI) and principal component analysis (PCA) supported the process of source apportionment. Findings showed that there was a strong spatial and temporal heterogeneity. The potentially bioavailable factions (F1 + F2 + F3) had maximums downstream at sites affected by urban activity cadmium at 1.95 mg/kg (81 %, SS5), lead at 5.81 mg/kg (72% SS7), and nickel at 5.37 mg/kg (100% SS7). The RAC more than 30% on cadmium showed increased mobility, and enhanced PERI (maximum of 285) on SS5 induced mainly by cadmium (E:241). The PCA revealed that 78% of the variance was explained, PC1 (54 %) linked cadmium and lead and nickel with anthropogenic urban runoff, and PC2 (24%) related geogenic iron and manganese with the remaining fraction F4. The Nworie and Otamiri river systems has a significantly high ecological risk. More studies focusing on the organization of fraction F3 and the following bioaccumulation mechanisms should be suggested to optimize the risk management approaches in this urban-tropical nexus.

Abstract: Forensic human identification relies on length-based differences in short tandem repeats (STRs) across autosomal and Y chromosomes, which require separate reactions and provide limited resolution. While next-generation sequencing offers greater discriminatory power, most platforms are expensive and restricted to traditional lab settings. Nanopore sequencing has the potential to change this with the real-time, portable MinION sequencer. However, forensic-specific tools that generate STR profiles compatible with established length-based databases are lacking. To address this, we developed STRspy2.0, which simultaneously profiles autosomal and Y-STRs using nanopore reads. STRspy2.0 produced accurate profiles for 54 multiplexed control libraries and 41 mock casework samples (blood, swab, bone), achieving overall F1-scores of 100% and 99.75%, respectively. It maintains compatibility with existing forensic databases while providing higher resolution than traditional profiles. Our updated method and comprehensive database, along with the MinION's small size and price, make sequence-based STR profiling more accessible to forensic laboratories and resource-limited settings.

Abstract: For decades, biologists have been struggling to determine the structure of proteins efficiently. They were experimenting to find a method to accurately predict protein structures from their amino acid sequence. As a result of this research, Google DeepMind was able to introduce a Deep Learning approach to predict protein structures. It is AlphaFold2. AlphaFold2 could grab the attention of biologists because of its high impact on human beings. Also, the Nobel Prize for chemistry in 2024 was offered for this breakthrough invention. However, even though AlphaFold2’s exceptional accuracy, it has some limitations. This comprehensive review provides a systematic analysis of the main limitations of the AlphaFold 2 framework. The AlphaFold2 struggles to predict multiple conformations for the same sequence, the effects of point mutations, and antigen-antibody interactions. And AlphaFold2 fails to predict protein-DNA and protein-RNA complexes, nucleic acid structure, ligand and ion binding, post-translational modifications, and membrane plane for transmembrane domains. By systematically reviewing these limitations, we can use this review as a roadmap for future research to improve the legendary AlphaFold2 framework for the well-being of human beings.

Abstract: Background/Objectives: Inherited retinal diseases (IRDs) represent a genetically heterogeneous group of disorders caused by mutations in over 280 genes with more than 3,100 identified variants. While gene-specific replacement therapies have achieved landmark success with voretigene neparvovec (Luxturna) for RPE65-associated retinal dystrophy, developing individual therapies for each genetic subtype remains impractical. This review examines gene-agnostic gene therapy approaches with neuroprotection and immunomodulation that target common pathophysiological mechanisms shared across multiple IRD genotypes. Methods: We reviewed the literature on neuroprotective and immunomodulatory gene therapy strategies for IRDs, focusing on neurotrophic factors and complement system modulation. Results: Neuroprotective approaches delivering neurotrophic factors—including pigment epithelium-derived factor (PEDF), ciliary neurotrophic factor (CNTF), rod-derived cone viability factor (RdCVF), brain-derived neurotrophic factor (BDNF), fibroblast growth factors, glial cell line-derived neurotrophic factor (GDNF), and proinsulin—have demonstrated photoreceptor preservation across multiple preclinical IRD models regardless of the underlying genetic mutation. The recent FDA approval of CNTF cell-based gene therapy (Encelto) for macular telangiectasia type 2 validates this therapeutic paradigm. Complement system inhibition represents another gene-agnostic strategy, with intravitreal complement inhibitors approved for geographic atrophy secondary to age-related macular degeneration and gene therapy approaches targeting C3, C5, or delivering soluble complement regulators under investigation for IRDs. Combination strategies simultaneously addressing multiple pathogenic pathways may offer synergistic benefits. Conclusions: Gene-agnostic approaches targeting neuroprotection and immunomodulation offer a scalable therapeutic paradigm capable of benefiting patients across the spectrum of IRD genotypes, potentially transforming treatment for conditions where mutation-specific therapies remain unavailable.

Abstract: Oxidative and nitrosative stress are central mechanisms in the pathogenesis of neurodegenerative diseases, where excessive production of reactive oxygen and nitrogen species (ROS/RNS) leads to mitochondrial dysfunction, membrane damage, and neuronal death. In this study, we established and compared short-term (2 h) and long-term (20 h) exposure paradigms to sodium nitroprusside (SNP), used as a xenobiotic nitric oxide donor, in two neuronal cell lines (mHippoE-18 and PC12) and zebrafish larvae, aiming to provide a preclinical framework for neurodegenerative drug discovery. In vitro, SNP exposure caused concentration-dependent reductions in viability and alterations in oxidative balance, with mHippoE-18 cells exhibiting higher susceptibility than PC12 cells. In the short-term exposure, cytotoxicity was primarily associated with membrane disruption at higher concentrations, while oxidative stress contributed more strongly at intermediate doses. In the long-term exposure, mHippoE-18 cells showed strong integrated correlations between ROS, LDH release, and viability loss, highlighting their vulnerability to nitrosative stress. In zebrafish, SNP exposure impaired metabolic activity and swimming behavior in both paradigms. Long-term exposure led to consistent dose-dependent increases in ROS, accompanied by locomotor deficits tightly linked to energy metabolism. Overall, the higher sensitivity of mHippoE-18 cells compared with PC12, and the dose-dependent metabolic and behavioral impairments observed in zebrafish, indicate that cellular responses partially mirror the in vivo outcomes. This integrative approach underscores the value of combining neuronal cell lines with zebrafish larvae to capture complementary aspects of SNP-induced neurotoxicity and to strengthen preclinical evaluation of candidate compounds with protective or therapeutic potential. These findings support the use of SNP as a xenobiotic model to probe nitrosative stress–driven neurotoxicity across cellular and organismal systems.

Abstract: Mangrove restoration is widely promoted as a nature-based solution to reverse coastal wetland degradation while sustaining fisheries productivity and other ecosystem services. This study evaluated whether a mangrove restoration program in Lubuk Kertang (North Sumatra, Indonesia) is associated with enhanced aquatic biodiversity and supporting water-quality conditions. Mangrove vegetation structure was assessed across restoration ages (2009–2013 plantings; 7–11 years old at the time of survey), and fish assemblages and water quality were sampled in June, August, and December 2021. We recorded 828 individual fishes representing 44 species, 27 families, and 17 orders. Fish diversity was moderate (mean Shannon–Wiener H′ = 2.15; evenness = 0.83; dominance = 0.17), with Engraulidae contributing the highest abundance. Water quality conditions were within ranges typical for estuarine mangrove habitats (DO 3.5–5.15 mg L⁻¹; pH 6.6–7.85; salinity 17.5–28.5; temperature 28.3–31.55 °C). Mangrove vegetation diversity indices were low to moderate (0.05–1.12) across restoration ages. These findings indicate that restored mangrove stands can function as aquatic habitat supporting diverse fish assemblages while maintaining basic water-quality conditions, reinforcing the role of mangrove restoration in sustainable coastal development and the Sustainable Development Goals (SDGs).

Abstract: Human papillomavirus (HPV) infection remains a major global health concern due to its strong association with cervical and other anogenital and oropharyngeal cancers. The outcome of HPV infection is largely determined by complex interactions between the virus and host immune responses. This review summarizes current knowledge on the immune landscape of HPV infection, focusing on innate immune recognition, adaptive immune responses, and viral immune evasion strategies. HPV is sensed by host pattern recognition receptors, yet it efficiently suppresses interferon signaling and cytokine responses to establish persistent infection. Adaptive immunity, including HPV-specific CD4⁺ and CD8⁺ T-cell responses and neutralizing antibodies, plays a critical role in viral clearance, while defects in these responses contribute to persistence and disease progression. The virus employs multiple immune evasion mechanisms, such as downregulation of antigen presentation and modulation of cytokine signaling, facilitating immune escape and oncogenesis. The review also highlights immune correlates of protection, vaccine-induced immunity, and emerging immunotherapeutic strategies targeting HPV-associated diseases. A comprehensive understanding of HPV–host immune interactions is essential for optimizing vaccine design, improving therapeutic interventions, and reducing the global burden of HPV-related malignancies.

Abstract: Milk is a primary source of vital nutrients and bioactive components fundamental for the growth and development of both newborn animals and humans. Produced by economi-cally significant livestock species (including cattle, buffaloes, goats, sheep and camels) milk is a complex matrix rich in caseins, vitamins, fats and proteins. In addition to its nu-tritional profile, milk serves as a vehicle for milk-derived extracellular vesicles (mEVs), a specialized class of food-derived EVs (fEVs) that exert pleiotropic effects aligned with the One Health concept, relating animal health, human nutrition, and ecosystem stability. mEVs offer unique advantages, such as high biocompatibility and gastrointestinal stabil-ity, rendering them also potential therapeutic tools, as drug delivery systems. However, challenges remain regarding the standardization of mEVs and the variability of their mo-lecular cargo. This review provides a comparative analysis of mEVs across diverse spe-cies, including bovines, water buffaloes, yaks, camels, goats, pigs, horses, donkeys, and humans, with a focus on their unique functional profiles. Indeed, a critical issue in mEVs research is the isolation process: recommendations to minimize contamination from milk fat globules and casein micelles (which can cover EV signals) are given. Finally, current detection methods and instrumentation, with a specific focus on advancing Flow Cytom-etry (FC) approaches are discussed. Key insights include the use of Conventional FC (with fluorescence triggering, the necessity of rigorous controls and calibration, and the utility of Bead-Based Assays to overcome resolution limits) and of Imaging Flow Cytometry (IFC). In both technical approaches, the application of different EVs generic fluorescent markers and the strategic selection of tetraspanins (i.e. CD9, CD63, CD81), is mandatory, empha-sizing the importance of selecting appropriate antibody clones or considering cross-reactivity when targeting these antigens across different mammalian species.

Abstract: Melanoma, a highly aggressive and metastatic cancer, poses significant challenges due to its propensity to spread to distant organs, with brain metastasis representing a particularly devastating complication. This review synthesizes recent advances in understanding the molecular, cellular, and microenvironmental mechanisms driving melanoma metastasis, with a specific emphasis on brain metastasis. We explore the unique challenges of brain metastasis, including blood-brain barrier penetration, brain-specific microenvironment interactions, and genomic distinctions. Advances in diagnostic tools, such as imaging and liquid biopsies, are discussed alongside current and emerging therapeutic strategies, including novel small molecules, immunotherapies, and combination approaches tailored for brain metastases. The review also highlights the immunological landscape of the brain, translational models, and multidisciplinary clinical management strategies. Finally, we identify critical research gaps, including the need for brain metastasis-specific clinical trials, AI-driven predictive models, and preventive strategies, to guide future efforts in improving outcomes for patients with melanoma brain metastasis.

Abstract:

Fermented foods are increasingly recognized for their potential to support gut and brain health via microbiome modulation. However, most research focuses on isolated probiotics or lab-prepared products, leaving limited evidence for real-world fermented foods with live bacteria. This study evaluated the effects of three commercially available fermented foods—dairy kefir, coconut kefir, and fermented red cabbage and beetroot—on gastrointestinal, cognitive, and emotional outcomes in healthy adults. Over a 4-week randomized controlled intervention, cognitive function was assessed using the CANTAB, emotional health via validated self-report measures, and stool samples analysed using the Genova Diagnostics GI Effects test. Dairy kefir improved decision-making, sustained attention, working memory, reduced depression, anxiety and stress. The coconut kefir reduced waiting impulsivity, enhanced short-term memory, improved total mood, and increased butyrate-associated commensals, Faecalibacterium prausnitzii, Bifidobacterium spp., Lactobacillus spp., and Anaerotruncus colihominis, alongside elevated butyrate levels. The fermented red cabbage and beetroot improved sustained attention, working memory, reduced stress, improved total mood, and increased both butyrate and propionate. In contrast, the control group showed a rise in Fusobacterium spp. These findings support fermented foods as functional dietary interventions for gut–brain health.

Abstract: Splicing defects represent a significant class of human genetic disorders, yet strategies to directly correct aberrant splice-site recognition remain limited. The small nuclear RNA U1 plays a critical role in pre-messenger RNA splicing by base-pairing with the conserved 5′ splice-site ‘GU’ dinucleotide. Disruption of this interaction can lead to abnormal splicing or frameshift mutations, contributing to disease pathology. Extracellular vesicles (EVs) can transport small, essential molecules to a cell for therapeutic applications. Thus, EVs were transfected with a U1 small nuclear RNA expression construct, resulting in approximately 120 nm diameter vesicles whose identity and purity were confirmed by the expression of several exosomal markers. When applied to HeLa cells expressing a β-globin minigene bearing a β-thalassaemia-like 5′ splice-site mutation, U1-enriched EVs corrected up to sixty percent of normal exon–intron junction recognition in a dose-dependent manner. Recovery was abolished by heat or RNase treatment, confirming that intact vesicular RNA cargo was essential for activity. These findings provide the first demonstration that EVs can transport spliceosomal small nuclear RNAs capable of reconstituting splice-site recognition in recipient cells and introduce a new class of RNA-based therapeutics that exploit the natural cargo-shuttling capacity of EVs to correct splicing defects associated with genetic disease.