CIC bioGUNE

Diagnostic delay is common in pediatric inflammatory bowel disease (PIBD), and fecal calprotectin (FCP) is often limited by challenges with sample collection. Therefore, we aimed to identify and validate a blood-based diagnostic protein signature of PIBD. Proteins were analyzed using proximity extension assay in plasma samples from treatment-naïve pediatric patients in a Swedish inception cohort referred for suspected inflammatory bowel disease (IBD) and validated in an independent Norwegian population-based pediatric inception cohort. Diagnostic performance was estimated by the area under the curve (AUC) with 95% confidence intervals (CIs). The discovery cohort included 58 patients with PIBD and 36 symptomatic controls without evidence of IBD, while the validation cohort consisted of 79 patients with PIBD and 37 symptomatic controls. In total, 154 proteins were examined. Univariable analyses identified 26 differentially regulated proteins for PIBD versus symptomatic controls in the discovery cohort (q < 0.05), whereas 29 proteins were differentially regulated in the validation cohort. Using regularized logistic regression, we identified a diagnostic model of 31 proteins that differentiated PIBD from symptomatic controls in the discovery cohort (AUC = 0.83; 95% CI: 0.74-0.90). The protein signature was further reduced to a clinically relevant biomarker consisting of high-sensitivity C-reactive protein (hsCRP) and seven other proteins with diagnostic capacity (AUC = 0.85, 95% CI: 0.78-0.92) outperforming hsCRP in the validation cohort (p = 0.006). We identified and validated a blood-based protein signature for PIBD with superior diagnostic performance compared to hsCRP. Given the challenges of fecal sample collection, further assay development may enable integration of these biomarkers into diagnostic pathways for PIBD. ClinicalTrials.gov identifier: NCT02727959.

Alcohol-associated hepatitis (AH) is the most severe clinical manifestation of alcohol-associated liver disease. Corticosteroids are the only disease-specific therapy shown to improve short-term survival. Currently, no non-invasive markers are available to predict patient response to corticosteroids or long-term survival in AH. This study investigates whether surface antigens on plasma extracellular vesicles (EVs), key mediators of intercellular communication, can reflect the underlying immune dysregulation in AH and serve as prognostic markers. Patients with AH were prospectively enrolled between 2020 and 2024. Blood samples were collected before corticosteroid initiation during the first 24 h of hospitalization. EVs were characterized using nanoparticle tracking analysis, cryo-electron microscopy, and flow cytometry. Interleukin-6 (IL-6), soluble (s)CD62p, Circulating Vascular Cell Adhesion Molecule-1 (sVCAM), tumor necrosis factor receptor superfamily member 1 (TNRFS1a), and Intercellular Adhesion Molecule 1 (ICAM-1) were quantified by ELISA. Key outcome variables included response to corticosteroids and mortality. A total of 46 patients with AH and 28 healthy donors (HD) were included. EV concentration was significantly higher in AH patients than in HD (9.3 × 1011 [IQR 4-24] versus 2.4 × 1011 [IQR 2-4], p = 0.03). Specific EV antigens were associated with key clinical outcomes: CD20 and CD2 levels differed between patients with or without infections (bacterial, viral, and fungal) developed during hospitalization; CD40 and CD146 were elevated in patients who developed acute kidney injury. EVs enriched in monocyte (CD14) and T-reg (CD25) markers were associated with plasma IL-6 levels, while endothelial markers CD105 and CD146 correlated with sVCAM and sCD62p. EVs enriched in platelet (CD49e) and endothelial (CD31) markers were associated with corticosteroid response, whereas EVs enriched with endothelial (CD105 and CD146) and B lymphocyte (CD19) markers were associated with mortality. Overall, EVs enriched in endothelial and monocyte markers may represent a candidate non-invasive tool for predicting corticosteroid response and mortality in AH, aiding risk stratification and early identification of non-responders for timely transplant evaluation.

ABSTRACTExtracellular vesicles (EVs) have emerged as powerful mediators of intercellular communication with significant potential across biomedical, veterinary, cosmetic, agricultural and environmental applications. However, the translation of EV‐based discoveries into practical and commercially viable products remains constrained by scientific complexity, regulatory uncertainty and manufacturing challenges. To address these barriers, the International Society for Extracellular Vesicles (ISEV) established the Translation, Regulation and Advocacy Committee (ISEV‐TRA). ISEV‐TRA aims to catalyse the responsible advancement of EV technologies by fostering cross‐sector collaboration, harmonising quality and regulatory frameworks and providing strategic advocacy to enhance market readiness. Through targeted initiatives—such as workshops and the development of translational resources and guidance—ISEV‐TRA seeks to bridge the gap between research and real‐world implementation. By promoting dialogue amongst academia, industry, investors and policymakers, ISEV‐TRA positions itself as a central driver in shaping the global roadmap for EV translation and commercialisation.

Conductive peptide nanowires are emerging as sustainable and biocompatible platforms for electronic devices, yet controlling their supramolecular organization remains challenging. Here we report the computational design, synthesis, and characterization of a pentameric tryptophan zipper peptide, (WQAWKAD)₅, which self-assembles into nanofibers featuring a core of π-stacked indole residues enabling electron delocalization to achieve efficient electron conduction. Structural analysis via molecular dynamics simulations, spectroscopy, and microscopy confirm the structural integrity and self-assembly of the tryptophan zippers into elongated fibers. Electrical measurements reveal temperature-activated electron transport consistent with hopping along the π-stacked aromatic core. Vacuum testing confirms intrinsic electronic conductivity by minimizing ionic and capacitive contributions, and the analysis of resistance as a function of channel length suggests that conduction is influenced by both, electron hopping along the fibers, and inter-fiber percolation effects. This study demonstrates that rationally designed self-assembled peptide nanowires can achieve controlled structural and electronic properties, highlighting their potential for bioelectronic applications and the development of modular, sustainable conductive biomaterials.

ABSTRACTExtracellular vesicles (EVs) are increasingly recognized as universal mediators of communication in nature across all domains of life and as versatile tools with roles spanning a wide range of industries. Although EVs have been extensively studied in biomedicine, mainly in diagnostic and nanotherapy of cancer and neurodegenerative diseases, their potential applications in other impactful society areas are only beginning to be explored. Microbial EVs contribute significantly to biofilm formation, virulence and the transmission of antibiotic resistance, highlighting their importance in pathogenicity and infection control. In the aesthetic and dermatological sectors, EVs are gaining traction as innovative agents for skin regeneration, anti‐ageing and inflammation modulation, with applications extending to cosmetic dermatology and non‐invasive treatments. Veterinary medicine is also exploring EVs for diagnostics and therapeutic delivery, while in agriculture, they show promise in improving crop resilience, acting as natural biopesticides and supporting plant–microbe interactions. Inter‐species and interkingdom EV communication understanding, potentially help pest control and disease prevention. Moreover, EVs are being investigated as biosensors for environmental pollution and as agents in soil and water remediation. In the food industry, EVs are explored for their functional benefits in promoting gut and systemic health. However, to fully realize their potential, challenges in large‐scale production, quality control and regulatory approval must be addressed. In this article, innovative solutions and potential of EVs across other health issues, environment, agriculture and biotechnology have been revised and discussed.

Chiral 1,2-aminoalcohols are privileged motifs in bioactive molecules, yet their stereocontrolled synthesis remains a challenge. Here, we report a general, metal-free photoredox Minisci strategy that converts bicyclic N,O-acetals derived from β-hydroxy-α-amino acids into enantiopure 2-hetaryl-1,2-aminoalcohols with complete stereoretention. This diastereoselective radical α-hetarylation proceeds under visible light and mild conditions, tolerating diverse substitution patterns on both the heteroarene and the bicyclic scaffold. Combined experimental and quantum mechanical studies reveal that dispersion (CH/π) interactions between the incoming heteroarene and the bridgehead methyl group govern the unexpected facial selectivity in the C-C bond-forming step. The products serve as versatile precursors to medicinally relevant scaffolds, and the scalability of the process highlights its synthetic utility. This work establishes a broadly applicable platform for the stereocontrolled radical functionalization of amino acid derivatives.

Prostate cancer is a prevalent tumor type that, despite being highly curable, progresses to metastatic disease in a fraction of patients, thus accounting for more than 350 000 annual deaths worldwide. In turn, uncovering the molecular insights of metastatic disease is instrumental in improving the survival rate of prostate cancer patients. By means of gene expression meta‐analysis in multiple prostate cancer patient cohorts, we identified a set of genes that are differentially expressed in aggressive prostate cancer. Transcription factor 19 (TCF19) stood out as an unprecedented epithelial gene upregulated in metastatic disease, with prognostic potential and negatively associated with the activity of the androgen receptor. By combining computational and empirical approaches, our data revealed that TCF19 is required for full metastatic capacity, and its depletion influences core cancer‐related processes, such as tumor growth and vascular permeability, supporting the role of this gene in the dissemination of prostate tumor cells.