Results 231 to 240 of about 2,805,831 (274)

Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference. [PDF]

open access: yesNat Genet
Meng X   +82 more
europepmc   +1 more source

KLF5 Downregulation Links Impaired BNIP3‐Mediated Mitophagy to Inflammatory Valve Remodeling in Calcific Aortic Valve Disease

open access: yesAdvanced Science, EarlyView.
In human CAVD, KLF5 is reduced in VIC‐rich regions and remodeling/stress‐associated VIC states. In VICs, KLF5 sustains BNIP3 promoter activity and BNIP3‐mediated mitophagy, thereby limiting cytosolic mtDNA accumulation. KLF5 loss weakens mitochondrial quality control and enhances mtDNA‐sensitive STING/NF‐κB/NLRP3 inflammatory signaling under osteogenic
Jin‐Hui Bian   +13 more
wiley   +1 more source

AS‐TLC‐Based High‐Throughput Screening Integrated with CuAAC Optimization Strategy Facilitates the Rapid Discovery of YTHDC1 Inhibitor

open access: yesAdvanced Science, EarlyView.
We developed Affinity Selection Thin‐Layer Chromatography (AS‐TLC) as a method for high‐throughput screening (HTS) of compound mixtures. Furthermore, we integrated activity assays with AS‐TLC and identified a YTH domain‐containing protein 1 (YTHDC1) inhibitor. Building on this hit, we applied copper(I)‐catalyzed azide–alkyne cycloaddition (CuAAC) click
Mingchen Wang   +19 more
wiley   +1 more source

An RNA‐Binding Protein RBMS1 Promotes Endothelial Cell Autophagy to Maintain Vascular Homeostasis and Suppress Deep Vein Thrombosis

open access: yesAdvanced Science, EarlyView.
RBMS1, an RNA‐binding protein, restores vascular endothelial homeostasis by enhancing ATG3‐mediated autophagy, thereby attenuating thrombus formation and suggesting a potential avenue for further therapeutic exploration in DVT. ABSTRACT Deep vein thrombosis (DVT) is a prevalent vascular disorder characterized by aberrant coagulation within the deep ...
Chu Chu   +13 more
wiley   +1 more source

Structural Basis of Shiga Toxin Neutralization by Human Antibodies Targeting Canonical Receptor‐Binding and Non‐Canonical Assembly Sites

open access: yesAdvanced Science, EarlyView.
Cryo‐electron microscopy structures reveal two distinct neutralization mechanisms of fully human monoclonal antibodies targeting the Shiga toxin 1a B subunit. RDS059 occludes the Gb3 receptor‐binding site, whereas RDS045 engages a lateral quaternary epitope to disrupt holotoxin assembly.
Jianting Ke   +10 more
wiley   +1 more source

Macrophage RSAD2 Couples mtDNA Synthesis With a Self‐Amplifying Inflammatory Circuit to Orchestrate Tissue Repair

open access: yesAdvanced Science, EarlyView.
Macrophage RSAD2 dually regulates CMPK2—the rate‐limiting enzyme for mitochondrial DNA synthesis—by suppressing its ubiquitination and promoting its phosphorylation via Csnk2a2 recruitment. This amplifies mtDNA production, which simultaneously activates a cGAS‐STING‐IRF3‐RSAD2 feedforward loop and the NLRP3 inflammasome, driving a self‐sustaining ...
Haomiao Yuan   +16 more
wiley   +1 more source

Restoration of m6A‐Modified circPSMB1 Suppresses Chordoma Progression and Enables Local Nanotherapeutic Intervention

open access: yesAdvanced Science, EarlyView.
An m6A‐modified circRNA, circPSMB1, is identified as a tumor suppressor in chordoma. METTL3‐dependent m6A promotes circPSMB1 interaction with HNRNPA2B1, limiting c‐MYC expression and malignant progression. An injectable HMnO2‐based nanohydrogel enables local circPSMB1 delivery and tumor microenvironment‐responsive therapy, offering a promising strategy
Yingchuang Tang   +7 more
wiley   +1 more source

Symbiont‐Induced HSP83 Establishes Two‐Tiered Control of Antifungal Immunity in an Invasive Beetle–Fungus Complex

open access: yesAdvanced Science, EarlyView.
In an invasive beetle–fungus complex, the mutualist Leptographium procerum induces host HSP83 and modulates Toll‐dependent antifungal immunity. HSP83 mediates two‐tiered control by associating with selected fungal recognition receptors and restraining Dorsal‐driven antimicrobial peptide transcription.
Qingtai Yang   +8 more
wiley   +1 more source

DIXDC1 Promotes Lymphatic Metastasis and Resistance to Cuproptosis in Bladder Cancer Through Mediating DLAT

open access: yesAdvanced Science, EarlyView.
DIXDC1 drives bladder cancer progression by binding and stabilizing DLAT. This axis enhances NEK7 and CCNE2 mRNA stability to promote proliferation and lymphatic metastasis, while limiting copper‐induced DLAT oligomerization to reduce cuproptosis sensitivity, identifying DIXDC1 as a potential target linking metastasis with cuproptosis resistance ...
Hongqiong Li   +17 more
wiley   +1 more source

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