Introduction: Flavonoid metabolism innovation is critical for seed plants’ terrestrial adaptation. Three key 2-oxoglutarate-dependent dioxygenase (2ODD) families—F3H, ANS, FLS—underpin flavonoid biosynthesis, but their evolutionary diversification mechanisms remain unclear. Methods: Comprehensive analyses were performed across 238 seed plant genomes, including phylogenetic/collinearity analyses, conserved motif detection, duplication-type classification, selection pressure assessment, and Brassica napus promoter/expression profiling. Results: These families originated from a common ancestral gene (ancestor X) and diversified via multiple duplications (TRD/WGD as primary drivers). Their evolution aligns with the EAC model, with subfunctionalization resolving ancestral multifunctionality. Structural conservation and lineage-specific motif variations support functional differentiation, and purifying selection predominates. Discussion: Our findings clarify the molecular evolutionary mechanisms of flavonoid pathway diversification, providing novel insights into the origin of flavonol and anthocyanin biosynthesis in seed plants.

An important area of interest for therapeutic development is the IL-1 superfamily, a critical group of immune regulators with profound implications in a variety of disorders. This study clarifies the evolutionary patterns of IL-1 family members by thoroughly analyzing more than 400 animal species, demonstrating their ancient roots that extend back to the earliest vertebrates. Important results show that, although IL-1 ligands expanded significantly over the evolution of mammals, their corresponding receptors remained remarkably structurally conserved. Identifying both lineage-specific adaptations and evolutionarily conserved residues provides vital information for treatment design. These findings point to the possibility of two different therapeutic strategies: addressing species-specific variants may allow for more targeted interventions, whereas focusing on conserved motifs may result in broad-acting treatments. The study also identified less well-known species as useful models for comprehending early immune systems. In addition to advancing our knowledge of the function of the IL-1 family in autoimmune, inflammatory, and carcinogenic illnesses, this research lays the groundwork for the development of more potent targeted therapeutics by creating an evolutionary framework for the IL-1 family.

Human umbilical cord mesenchymal stem cells (UC-MSCs) are one of the most extensively researched stem cell types due to their potential for multi-lineage differentiation, secretion of regenerative factors, modulations of immunological activities, and the release of regenerative substances and influence immunological processes. Since UC-MSCs must be cultivated on a large scale for clinical use, selecting the appropriate storing passage, such as the usage-based passage of UC-MSCs, is critical for long-term autologous or allogeneic usage. Long-term cultivation of stem cells, on the other hand, causes them to lose their pluripotent differentiation capacity. As a result, distinguishing between high and low passages of UC-MSCs and identifying the particular variations associated with stem cells and their modes of action is essential for regenerative medicine. Therefore, we investigated the biological features and transcriptional changes of UC-MSCs over passages. UC-MSCs were isolated from the tissues of the human umbilical cord, and UC-MSCs from five passages (P1, P3, P5, P10 and P15) with three repetitions were compared and identified based on morphology, cell markers, differentiation capacity, and aging-related characteristics. It was previously assumed that the phenotype of cells before the P10 passage was stable, defined as early passage, and that culture could be continued until the 15th passage, defined as late passage. Next, the five passages of UC-MSCs were sequenced using high-throughput complete transcriptome sequencing. Fuzzy C-Means Clustering (FCM) and Weighted Gene Co-expression Network Analysis (WGCNA) were used to find hub genes, and gene silencing was performed to investigate the impact of missing genes on the stemness of UC-MSC cells. UC-MSCs of different passages displayed similar surface markers, including CD73, CD105, CD90, CD34, CD45 and HLA-DR. However, the proliferation time of late-phase UC-MSCs was longer than that of early-phase UC-MSCs, and the expression of the senescence-associated (SA)-β-gal staining marker was higher. At the same time, pluripotency markers (NANOG, OCT4, SOX2 and KIF4A) were down-regulated, and the multi-differentiation potential was reduced. Meanwhile, KIFC1 and UBE2C were down-regulated in late-phase UC-MSCs, which were involved in the maintenance of stemness. KIFC1 and UBE2C were highly expressed in early-UC-MSCs and showed a downward gradient trend with cell expansion in vitro. They regulated UC-MSC proliferation, colony sphere formation, multiple differentiation, stemness maintenance, and other biological manifestations. Therefore, they are anticipated to be new biomarkers for UC-MSCs quality identification in regenerative medicine applications.

Background: The interleukin-10 (IL-10) signaling system, comprising ligands (IL-10s) and receptors (IL-10Rs), plays critical roles in immune regulation, inflammation resolution, and disease pathogenesis. “IL-10 signaling system” here refers to the immunomodulatory signaling system composed of ligands (IL-10s) and receptors (IL-10Rs), which belong to different Protein families in evolution, but achieve functional synergy through the conserved JAK-STAT pathway. Understanding their evolutionary and functional dynamics is essential for elucidating immune mechanisms and therapeutic targeting. Methods: Through phylogenetic reconstruction, homology analysis, and sequence alignment across >400 animal species, we traced the evolutionary trajectory and structural–functional diversification of IL-10s and IL-10Rs. Results and Conclusions: IL-10 signaling components emerged in early vertebrates, with IL-10Rs originating in cartilaginous fishes (~450 Mya) and IL-10s diversifying in bony fishes (~400 Mya). Functional divergence yielded immunosuppressive (IL-10), barrier-protective (IL-20 subfamily), and antiviral (type III IFN) subgroups. Structurally, conserved motifs (e.g., IL-10R1 GYXXQ, IL-22 N54-glycosylation) underpin receptor–ligand binding and JAK/STAT signaling. Evolutionarily invariant residues suggest candidate therapeutic epitopes. This study provides an evolutionary framework highlighting functional conservation and species-specific adaptation within IL-10 signaling, with implications for immunotherapy and animal breeding.