Results 121 to 130 of about 33,034 (254)

Identification of an Osteochondral Erosion Process in Gout Driven by Fibrinogen‐Integrin Activation and Local MSU Crystallization

open access: yesAdvanced Science, EarlyView.
Cartilage injury promotes local fibrinogen deposition, which accelerates monosodium urate crystallization and activates integrin‐mediated matrix‐degradation. This self‐amplifying cycle drives gout‐related cartilage erosion. Disrupting fibrinogen deposition or restoring the cartilage barrier could interrupt this vicious cycle.
Hanlin Xu   +7 more
wiley   +1 more source

Introducing Borsantrazole: A Trifunctional Boron‐Based Pyrazole That Extends the Lifespan of Amyotrophic Lateral Sclerosis Mice

open access: yesAdvanced Science, EarlyView.
Herein we report a boron‐based pyrazole, (Borsantrazole ‐ a small molecule that selectively targets oxidative stress) that significantly increases survival, reduces weight loss, delays disease onset, and affects global protein changes in the SOD1‐G37R mouse model of ALS.
Nitesh Sanghai   +9 more
wiley   +1 more source

PFKFB4 Deubiquitination by USP10 Enhances Fumarate Metabolism to Orchestrate the KDM1A/Rad51 Axis and Confer Radioresistance in Lung Cancer

open access: yesAdvanced Science, EarlyView.
USP10 binds to and stabilizes PFKFB4, enhancing glycolytic ATP production, which activates the urea cycle and elevates fumarate. This inhibits histone demethylase KDM1A, leading to increased H3K4me1 enrichment at the Rad51 promoter and direct activation of Rad51 transcription, which confers lung cancer radioresistance. The PFKFB4 inhibitor 5MPN targets
Yunshang Chen   +7 more
wiley   +1 more source

LRRC4 Orchestrates AP2A1‐Containing Clathrin‐Coated Vesicles to Disrupt Mitochondrial Cristae and Restrict Glioblastoma Progression

open access: yesAdvanced Science, EarlyView.
LRRC4 suppresses GBM by regulating AP2A1‐containing Golgi‐derived clathrin‐coated vesicles. Low LRRC4 allows cytoplasmic AP2A1 to maintain mitochondrial fission‐fusion, MICOS integrity, and OXPHOS, promoting proliferation and invasion. High LRRC4 redirects AP2A1‐containing Golgi‐derived clathrin‐coated vesicles to mitochondria, disrupts MICOS, enhances
Yang Li   +5 more
wiley   +1 more source

Kaempferol Attenuates Spaceflight‐Associated Knee Cartilage Degradation by Targeting NOX4‐Mediated Mitochondrial Dysfunction

open access: yesAdvanced Science, EarlyView.
We have shown that both simulated and actual spaceflight contribute to cartilage degradation in the knees of mice. Using RNA sequencing and bioenergetic profiling, we identified NADPH oxidase 4 (NOX4) as a key factor driving these changes. Additionally, we found that kaempferol, a naturally occurring flavonoid that binds directly to NOX4, reduces ...
Yuesong Yin   +23 more
wiley   +1 more source

Real‐Time Ferroelectric Domain Wall Dynamics During Electric Poling and Depoling

open access: yesAdvanced Science, EarlyView.
Real‐time visualization of domain wall dynamics during alternating‐current poling, direct‐current poling, and electrical depoling in relaxor‐PT ferroelectric single crystals reveals distinct field‐dependent pathways and strong path dependence. Instant polarized light microscopy uncovers reversible domain wall nucleation, motion, and reconfiguration ...
Ziqi Wang   +12 more
wiley   +1 more source

Cell‐Selective Delivery of RIBOTACs via an Anti‐EGFR Nanobody for Pancreatic Cancer Treatment

open access: yesAdvanced Science, EarlyView.
This study introduces an innovative strategy for the tumor‐selective catalytic degradation of oncogenic non‐coding RNA by interfacing a ribonuclease‐recruiting small molecule (RIBOTAC) with an EGFR‐targeting nanobody via a CTSB (Cathepsin B)‐responsive linker.
Tianli Luo   +15 more
wiley   +1 more source

A Supramolecular Thermal Switch for Precision Pyroptosis via Host−Guest Recognition and Electrostatic Interactions

open access: yesAdvanced Science, EarlyView.
A supramolecular pyroptotic thermal switch encapsulates I3− within β‐cyclodextrin (β‐CD) and undergoes CaCO3 mineralization. Upon lysosomal acidification, CaCO3 is degraded, releasing Ca2+ and I3−. Concurrently, BODIPY activation converts I3− into I2, inducing oxidative stress and Ca2+ overload, which together trigger caspase‐3/GSDME‐mediated ...
Dan Wu   +8 more
wiley   +1 more source

Aberrant GRP78 Phase Transition Sustains Endothelial IRE1α Signaling and Drives Blood–Brain Barrier Failure in Cerebral Amyloid Angiopathy

open access: yesAdvanced Science, EarlyView.
Vascular Aβ40 corrupts GRP78 phase behavior in brain endothelial cells, sustaining IRE1α–TRAF2–JNK signaling and driving apoptosis, tight junction loss, and blood–brain barrier failure in cerebral amyloid angiopathy. Pharmacological IRE1α inhibition restores vascular integrity, reduces leakage, and improves functional outcomes, revealing a targetable ...
Honglin Zheng   +19 more
wiley   +1 more source

Computation and Structure‐Guided Arginine Scanning Engineers a Hyperactive AP Endonuclease for Multiplex Viral RNA Sensing

open access: yesAdvanced Science, EarlyView.
Computational and structure‐guided arginine scanning rewires the DNA‐binding interface of APE1 to create APE1‐Evo, a hyperactive yet specific AP endonuclease. Integrated into the NAPTUNE‐V2.0 cascade, APE1‐Evo enables amplification‐free, multiplex viral RNA sensing for dengue virus and influenza A/B, highlighting a general strategy for engineering ...
Junlan Wang   +20 more
wiley   +1 more source

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