Results 231 to 240 of about 28,338 (304)

NPM1 Mediates mRNA Sorting into Extracellular Vesicles via Specific RNA Motif Binding and Phase Separation

open access: yesAdvanced Science, EarlyView.
NPM1 selectively sorts specific mRNAs into extracellular vesicles (EVs) by recognizing RNA motifs and forming phase‐separated condensates. These mRNA cargos—including EGFR—are then loaded via multivesicular bodies. This active sorting pathway, validated in EVs derived from both lung cancer cells and patient serum, reveals a specific mechanism for ...
Kaixiang Zhang   +8 more
wiley   +1 more source

Endogenous “Time Bomb” – Mislocalized Phospholipase A2 as a Critical Mediator of Ultra‐Rapid Mortality in Sepsis and Acute Lung Injury

open access: yesAdvanced Science, EarlyView.
Phospholipase A2 (PLA2), a dormant enzyme, becomes lethal when activated—collapsing lungs in minutes. Our dual therapy (DOPS + varespladib) boosts survival from 0% to >90% in sepsis/ALI. A breakthrough for acute lung injury treatment. ABSTRACT This study reveals that phospholipase A2 (PLA2), normally stable and nontoxic, can be activated specifically ...
Jianyu Wang   +7 more
wiley   +1 more source

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

De Novo Design and Directed Evolution Refinement of Mirror‐Image Protein Binders Targeting Interleukin‐4

open access: yesAdvanced Science, EarlyView.
This study presents the de novo design and directed evolution of a mirror‐image D‐protein inhibitor targeting human interleukin‐4 (IL‐4). The engineered molecule exhibits nanomolar binding affinity for IL‐4 and effectively inhibits IL‐4–mediated signaling.
Liqing Xu   +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

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