Biomolecules

Cerebral amyloid-β (Aβ) burden in Alzheimer’s disease (AD) reflects the balance among peptide production, degradation, movement between compartments and retention within cerebral vessel walls. Across the reviewed evidence, cerebrovascular adaptation was the most consistently observed exercise response, although its direction and measurement varied across studies and it did not by itself establish Aβ removal. Direct evidence for exercise-related Aβ movement was narrower and predominantly preclinical. Animal studies report improved vascular responsiveness, blood–brain barrier-related phenotypes and aquaporin-4-sensitive fluid exchange; selected tracer experiments further show greater short-term recovery of brain-administered Aβ in blood, lymphatic or peripheral compartments. Cellular and peripheral studies identify candidate routes for the degradation and downstream handling of redistributed peptide. Human trials generally show improved fitness or cerebrovascular function without clear between-group changes in Aβ-PET or plasma Aβ over the measured periods. The pattern is compartment- and timescale-specific: functional adaptation and measured amyloid burden capture different components of the exercise response. Source-matched recovery in a downstream compartment, when coupled with a time-resolved decline in the same brain-derived signal, can establish net removal from the brain but not whole-body terminal disposal; the latter requires verified irreversible degradation or excretion of the tracked peptide. The sustained net removal of endogenous brain Aβ also requires a concurrent assessment of production and vessel-wall retention. Overall, cerebrovascular and fluid-transport adaptation is the best-supported exercise-responsive context for Aβ disposition, whereas neither sustained net removal of brain Aβ nor whole-body terminal disposal has been established in human exercise studies.

Background: Cirrhosis is characterized by persistent systemic inflammation and immune dysregulation, both contributing to disease progression and poor clinical outcomes. Readily available inflammatory biomarkers have been proposed as complementary tools for disease severity assessment; however, data in alcohol-related cirrhosis remain limited. This study aimed to evaluate the association between inflammatory markers and established severity scores in patients with alcohol-related cirrhosis. Methods: This prospective cross-sectional observational single-center study included 114 consecutively enrolled patients with alcohol-related cirrhosis (mean age 58.48 ± 9.09 years; 77.19% male) at the Gastroenterology/Internal Medicine I Department of the Emergency Clinical Hospital of Craiova between September 2024 and February 2025. Inflammatory biomarkers, including C-reactive protein, ferritin, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII), were analyzed in relation to Child–Pugh and MELD scores. Correlation and regression analyses were performed to assess their associations with disease severity. Results: CRP, ferritin, NLR, and LMR showed significant correlations with both Child–Pugh and MELD scores, whereas PLR and SII were not significantly associated with disease severity. In multivariable analyses, ferritin remained significantly associated with both Child–Pugh and MELD severity, whereas LMR remained significantly associated only with Child–Pugh severity. Overall, correlations were numerically stronger for Child–Pugh with CRP and LMR, whereas ferritin and NLR showed a slightly stronger correlation with MELD. Conclusions: Several inflammatory biomarkers were associated with established severity scores in alcohol-related cirrhosis, with ferritin showing the most consistent association across both scoring systems. These findings support the relationship between systemic inflammation and disease severity in alcohol-related cirrhosis.

Wool fibre diameter is a key economic trait in wool-producing animals, and its formation is regulated by the synergistic interaction between the proliferation and differentiation of hair follicle stem cells (HFSCs) and signals from the microenvironment. Dermal papilla cells (DPCs), as a key signal source, regulate the fate of HFSCs via paracrine pathways; however, the key molecular mechanisms remain unclear. Single-cell RNA sequencing (scRNA-seq) and genome-wide association studies (GWAS) revealed that ZNF280B is specifically expressed in both DPCs and HFSCs, and its g.677G>A variant is significantly associated with wool fibre diameter. Functional studies indicate that overexpression of ZNF280B promotes the proliferation of DPCs and HFSCs and inhibits apoptosis, whilst knockdown has the opposite effect; mechanistically, ZNF280B alters mRNA levels of key marker genes of the Wnt/β-catenin signalling pathway while selectively changing transcripts of the TGF-β pathway components in DPCs, and differentially modulates key marker transcripts in both the Wnt/β-catenin and Notch pathways in HFSCs. In summary, ZNF280B mediates the paracrine signalling of DPCs to influence HFSC proliferation and differentiation. It achieves this by integrating the Wnt/β-catenin/TGF-β/Notch signalling axes. This reveals that ZNF280B acts as an important regulatory node mediating DPC-HFSC paracrine communication, and provides new insights into the developmental mechanisms of fine-wool hair follicles and molecular breeding for fibre diameter.