Results 271 to 280 of about 131,627 (329)

Single‐Cell Atlas of Subchondral Bone Marrow Lesions Reveals Proteostasis Dysfunction as a Druggable Mechanism for Early Osteoarthritis

open access: yesAdvanced Science, EarlyView.
This study reveals that abnormal mechanical stress downregulates the expression of HSP70 and impairs proteasome function in osteoarthritic bone cells, leading to misfolded collagen I accumulation and ER stress. When intracellular proteostasis capacity is exceeded, USP19 mediates the secretion of misfolded proteins into the extracellular space ...
Hailun Xu   +20 more
wiley   +1 more source

Respiratory‐Limbic Coupling via a Thalamic Circuit Alleviates Anxiety

open access: yesAdvanced Science, EarlyView.
This study delineates a conserved preBötCGlu→PVT→CeA circuit that gates anxiety and respiration. Activation of this circuit is anxiolytic and respiratory‐stabilizing, while its inhibition has the opposite effect. Mechanistically, PVT exerts its anxiolytic action via a disinhibitory microcircuit: its inputs preferentially target CeL GABAergic neurons ...
Shangyu Bi   +15 more
wiley   +1 more source

Intracellular Aβ42 Sequestration by a Serine Protease Mitigates Neurotoxicity in a Drosophila Alzheimer's Disease Model

open access: yesAdvanced Science, EarlyView.
Emerging evidence suggests that intraneuronal Aβ accumulation represents an early pathogenic event in Alzheimer's disease (AD). Using Drosophila AD model, this study shows that a nonsecreted serine protease Yip7 physically interacts with Aβ. This causes intraneuronal Aβ accumulation but surprisingly reduces the associated neurotoxicity, arguing that ...
Jingyun Su   +4 more
wiley   +1 more source

Targeted H2S Delivery System Attenuates Blood‐Spinal Cord Barrier Disruption after Spinal Cord Injury by Reshaping the Ferritinophagy Pathway

open access: yesAdvanced Science, EarlyView.
The αvβ3‐mediated SPRC@MPDA‐RGD targets broken endothelial cells and controllably releases SPRC. CSE is then activated to produce endogenous H2S, which inhibits ferritinophagy. In brief, H2S inhibits autophagy by activating the PI3K/Akt/mTOR pathway, thereby suppressing the ferroptosis process mediated by NCOA4, and ultimately promoting the ...
Zhiheng Chen   +11 more
wiley   +1 more source

Adipocyte‐Derived Exosomal miR‐5099 Mitigates M1 Macrophage Polarization and Adipose Inflammation via c‐Met/NF‐κB Axis to Improve Metabolic Health

open access: yesAdvanced Science, EarlyView.
Celastrol upregulates adipocyte‐derived exosomal miR‐5099, suppressing the macrophage c‐Met/NF‐κB axis to mitigate pro‐inflammatory M1 polarization and adipose inflammation. These miR‐5099‐enriched exosomes also act as endocrine signals targeting the liver, muscle, and adipocytes to significantly enhance systemic insulin sensitivity.
Ping Tang   +9 more
wiley   +1 more source

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