Results 101 to 110 of about 9,150 (262)

Discovery of SKP2‐Recruiting PROTACs for Target Protein Degradation

open access: yesAdvanced Science, EarlyView.
Based on the SKP2‐targeting ligand SL1, we designed non‐covalent PROTACs by linking it with the BRD4 inhibitor JQ1 and the AR antagonist AL through a linker. These PROTACs successfully induced the ubiquitination of BRD4 and AR, followed by proteasome‐mediated degradation.
Guanjun Dong   +13 more
wiley   +1 more source

Decoding Triphenotypic Neutrophils in Cervical Cancer Evolution and Targeting SPP1+/GBP1+/ELOVL5+ Tumor‐Associated Neutrophils to Sensitize Immunotherapy

open access: yesAdvanced Science, EarlyView.
The functional schematic diagram of tumor associated neutrophils. Abstract Enhancing cervical cancer (CC) immunotherapy requires deciphering the heterogeneous tumor immune microenvironment (TIME), particularly neutrophil phenotypic dynamics. Here, 1) we collected 543 CC cases to find that patients with elevated neutrophil levels have a higher incidence
Xingyu Chang   +7 more
wiley   +1 more source

Deciphering and Targeting the Schwannoma‐Neuron‐Macrophage Crosstalk for the Treatment of Schwannomatosis and Associated Pain

open access: yesAdvanced Science, EarlyView.
We established patient‐derived SWN cell lines and orthotopic PDX models that recapitulate patient pain phenotypes, alongside a novel intravital DRG imaging platform to track macrophage infiltration and neuronal pain responses. Using these models, we define HMGB1–CCL2–IL‐6 signaling crosstalk driving pain and identify EGF signaling as a key regulator of
Zhenzhen Yin   +17 more
wiley   +1 more source

An Insulin‐Exosome‐TNFAIP8 Axis Drives Stromal Fibrosis and Therapeutic Resistance in Pancreatic Cancer

open access: yesAdvanced Science, EarlyView.
In pancreatic ductal adenocarcinoma (PDAC), insulin is associated with activation of PI3K/AKT–RAB3A signaling and enhanced secretion of TNFAIP8‐enriched exosomes from tumor cells. Uptake of these exosomes by fibroblasts is linked to TRIM21‐dependent STAT1 degradation and the emergence of myofibroblastic CAF–associated features, accompanied by increased
Zhenyu Li   +15 more
wiley   +1 more source

HSP90AB1‐Mediated Ubiquitin‐Proteasome Degradation of ITGBL1 Promotes Osteosarcoma Progression by Inhibiting Endoplasmic Reticulum Stress‐Induced Autophagy

open access: yesAdvanced Science, EarlyView.
This study delineates a novel HSP90AB1‐ITGBL1 signaling axis governing osteosarcoma. HSP90AB1 promotes K63‐linked ubiquitination and proteasomal degradation of ITGBL1. Restoring ITGBL1 induces reactive oxygen species‐dependent endoplasmic reticulum stress and pro‐death autophagy, suppressing tumor growth and metastasis.
Zhen Wang   +17 more
wiley   +1 more source

Real‐Time Visualization of Isoform‐Specific RAF‐KRAS Interactions in Living Cells Using FRET‐BRET Hybrid Biosensors

open access: yesAdvanced Science, EarlyView.
Hybrid FRET–BRET biosensors were developed to monitor RAF–KRAS interactions in living cells. These sensors enable real‐time visualization of interaction dynamics, quantitative spectral analysis, and validation of mutation‐selective inhibitors, providing a versatile platform for probing KRAS regulation and therapeutic responses. ABSTRACT The RAS–RAF–MEK–
Jeong‐Min Go   +12 more
wiley   +1 more source

Lipid‐Facilitated Opening of the ADAM10 Sheddase Revealed by Enhanced Sampling Simulations

open access: yesAdvanced Science, EarlyView.
Phosphatidylserine acts as a lipid trigger to enhance activation of the sheddase ADAM10. By integrating fluorescence spectroscopy assays with enhanced sampling molecular dynamics simulations, this study shows that phosphatidylserine promotes ADAM10 catalytic activity along with expansion of its extracellular domains, enhancing accessibility to scaffold
Adrien Schahl   +7 more
wiley   +1 more source

De Novo Multi‐Mechanism Antimicrobial Peptide Design via Multimodal Deep Learning

open access: yesAdvanced Science, EarlyView.
Current AI‐driven peptide discovery often overlooks complex structural data. This study presents M3‐CAD, a generative pipeline that leverages 3D voxel coloring and a massive database of over 12 000 peptides to capture nuanced physicochemical contexts.
Xiaojuan Li   +23 more
wiley   +1 more source

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