Twenty-four compounds, comprising six triterpenoid saponins, six flavonoids, four coumarins, three lignans, two phenylpropanoids, one N-cyclohexylamide, one macrocyclic and a steroid, were isolated from the aerial parts of Clematis terniflora DC. (Ranunculaceae) and characterized through spectral analysis and comparison with literature data. All compounds were firstly isolated from this plant. Acacetin 7-O-(3-O-acetyl)-/3-D-glucopyranoside (11), cleomiscosin D (15), hemidesmin 1 (16) and N, N' -dicyclohexylurea(22) were isolated from Ranunculaceae plants for the first time. The chemotaxonomic significance of these compounds is also discussed herein.
Hepatic osteodystrophy (HOD) is a debilitating metabolic bone disorder inextricably linked to chronic liver disease, with its prevalence surging alongside the global rise of metabolic dysfunction-associated steatohepatitis (MASH). Current clinical interventions remain fragmented, failing to concurrently address the upstream hepatic lipotoxicity and the downstream skeletal deterioration. Herein, we engineer copper-doped bioactive glasses (CuBGs) as a multifunctional ion-therapy nanoplatform that exploits natural hepatic tropism to synchronously rescue MASH-HOD pathology via targeted reprogramming of the liver-bone axis. By delivering localized therapeutic ions, CuBGs orchestrate robust hepatic metabolic recovery: they enhance glucose tolerance and restore mitochondrial oxidative phosphorylation (OXPHOS), thereby effectively halting intrahepatic triglyceride accumulation and quenching ROS-driven inflammation. Crucially, this hepatic rescue reactivates the liver-bone endocrine crosstalk by robustly upregulating the secretion of the hepatokine lecithin-cholesterol acyltransferase (LCAT). Systemic LCAT restoration directly stimulates profound osteoblastogenesis and new bone formation, decisively reversing MASH-induced trabecular bone loss without acting as a conventional anti-resorptive agent. This dual-organ modulation comprehensively ameliorates the interconnected multi-organ microenvironment in MASH-HOD without inducing systemic toxicity. Ultimately, this bioactive glass-mediated copper delivery system establishes a novel, highly scalable strategy for ion-based nanotherapeutics, offering a promising and integrated strategy for complex liver-bone comorbidities.
The matrix protein 2 (M2) is one of the most representative and widely studied ion channel proteins, which plays broad biological roles in the life cycle of the influenza A virus. The M2 protein affects the function of host cells and the regulation of cellular homeostasis in an ion channel activity-dependent or-independent manner and it is also the target for anti-influenza virus drugs, such as amantadine and rimantadine. The focus of this review is to summarize the research progress on the M2 protein, such as structure and function, vaccine and drug development as well as antagonist of host innate immune responses. A particular emphasis is placed on the multifaceted roles of M2 beyond canonical ion conduction. Specifically, M2 modulates the MAVS pathway through direct interaction with MAVS and by inducing ROS production, which amplifies interferon-mediated inflammation while paradoxically disrupting autophagic degradation of MAVS aggregation. Concurrently, the M2 protein orchestrates autophagy regulation by inhibiting autophagosome-lysosome fusion and initiating AKT-mTOR signaling, thus stabilizing the viral polymerase to enhance viral replication. A comprehensive understanding of these mechanisms is essential for advancing universal M2-based vaccine strategies and novel host-directed antiviral therapies.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading chronic liver condition affecting nearly 40
BACKGROUND:Over 25% of patients with ulcerative colitis (UC) develop extraintestinal manifestations (EIMs), resulting in significant systemic morbidity. We define the shared genetic foundation of these manifestations as the UC-associated Multisystem Inflammatory Genetic Architecture (UC-MIGA). This study aims to identify shared genomic drivers and actionable immunosenescence therapeutic targets across the UC-EIM spectrum. METHODS:We applied genomic structural equation modeling (SEM) to seven European-ancestry GWAS datasets (UC, deep vein thrombosis, ankylosing spondylitis, primary sclerosing cholangitis, pyoderma gangrenosum, interstitial lung disease, and erythema nodosum) to identify a shared latent genetic factor (F1). Post-SEM analyses included FUMA mapping, SuSIE/FINEMAP fine-mapping, FUSION/FOCUS transcriptome-wide studies, MAGMA enrichment, CELLECT deconvolution, LDSC partitioned heritability, and single-cell eQTL Mendelian randomization (MR). UC exhibited the highest standardized factor loading (0.9801) on F1, justifying its use as a representative proxy for UC-MIGA in downstream analyses. UC-telomere relationships were assessed via tissue-specific eQTL/sQTL enrichment across 49 GTEx tissues, spatial transcriptomics (gsMap), single-cell profiling (GSE214695, GSE163974), hdWGCNA, and colocalization analyses (eCAVIAR, fastENLOC). RESULTS:SEM identified substantial genetic overlap (CFI = 1.0, SRMR = 0.17). Within the UC-MIGA framework, we identified 17,005 SNPs (P ≤ 1 × 10⁻2⁰⁰), 2,622 risk loci, and 152 high-confidence effector genes. Pathways implicated Th17/Treg imbalance and inflammasome signaling. Super-enhancer regions showed exceptional heritability enrichment (80.16%, fold = 4.79, p = 0.0007). MR identified 35 causal immune cell-gene associations. UC-telomere analyses revealed convergence in colon-specific DNA repair-mitochondrial energetics-telomere maintenance pathways, with B cells prioritized as the core cell type. Colocalization identified NKX2-3 and LINC01475 as high-confidence shared candidates. Embryonic intestinal enrichment supported the developmental origins of this systemic axis. CONCLUSION:UC-MIGA represents a genetically coherent architecture driven by super-enhancer-mediated epigenetic dysregulation, Th17/Treg imbalance, and immunosenescence features, including telomere dysfunction and B-cell exhaustion. The 'developmental vulnerability-environmental trigger' model explains the gut-origin inflammatory cascade underlying extraintestinal manifestations, with UC-telomere analysis providing a genomic foundation for systemic therapeutic strategies targeting the inflammation-aging nexus.
