Results 121 to 130 of about 12,027,294 (272)

A Novel Pak1 Activator Ameliorates ER Stress for HFpEF Therapy

open access: yesAdvanced Science, EarlyView.
Chronic metabolic stress is a major contributor to HFpEF progression. Under prolonged metabolic stress, Pak1 activity becomes impaired, contributing to disrupted ER proteostasis, cardiomyocyte apoptosis, fibrosis, and diastolic dysfunction. Mechanistically, Pak1 overexpression activates the ERK1/2–MNK1–eIF4E signaling axis, promotes translational ...
Honglin Xu   +17 more
wiley   +1 more source

VlPAG/DRN Microglia Drive Neuropathic Pain‐Induced Depression via a Defined Neuroimmune Axis

open access: yesAdvanced Science, EarlyView.
Peripheral nerve injury (SNI) induces neuropathic pain, activates midbrain microglia, and triggers an NLRP3–IL‐1β–dependent inflammatory cascade. IL‐1β signals through IL‐1R1 on vlPAG/DRN VGLUT2+ neurons (vlPAG/DRNGlu), inducing hyperexcitability and driving the vlPAG/DRNGlu→BNSTGABA circuit to produce the affective component of neuropathic pain ...
Jing Yang   +7 more
wiley   +1 more source

Regulating Cells Fate and Function to Facilitate Bone Regeneration via Designing Programmable Bio‐Interactive Materials

open access: yesAdvanced Science, EarlyView.
This article aims to elucidate the biological mechanisms of bone repair and the evolution of material design, highlighting key cellular and molecular processes. It further proposes strategies and prospects for programmable bio‐interactive materials, which enable precisely guided bone tissue regeneration by dynamically regulating cell behavior and the ...
Qingrui Fan   +6 more
wiley   +1 more source

A Multidimensional Engineering Strategy Reprograms Microglia via Targeted and Sustained‐Release Extracellular Vesicles for Spinal Cord Injury Repair

open access: yesAdvanced Science, EarlyView.
A multifunctional EV‐based nanoplatform (Ang‐TEVs@Gel) was engineered via preconditioning, surface targeting, and ROS‐responsive hydrogel encapsulation to reprogram microglia. This system restored autophagy via miR‐664a‐3p/PIK3CA axis, cleared myelin debris, resolved neuroinflammation, and promoted axon remyelination, ultimately achieving robust motor ...
Wu Xiong   +17 more
wiley   +1 more source

A Decoy‐Receptor‐Armed Biomimetic Nanotherapeutic With Inherent Tropism for Conserved Pathogenic Macrophages for Treating Osteoarthritis and Intervertebral Disc Degeneration

open access: yesAdvanced Science, EarlyView.
A biomimetic doppelgänger nanosystem neutralizes extracellular inflammatory cytokines and silences intracellular pyroptosis, reprogramming pathogenic macrophages to attenuate both joint and spine degeneration. ABSTRACT Osteoarthritis (OA) and intervertebral disc degeneration (IVDD) are debilitating musculoskeletal disorders driven by shared ...
Fudong Li   +9 more
wiley   +1 more source

ZBTB18 Dysfunction Promotes Neuropathic Pain via CHD4‐based Epigenetic Disinhibition of CLIC1 Channels in Sensory Neurons

open access: yesAdvanced Science, EarlyView.
In this study, we identify a novel functional role of ZBTB18 in regulating trigeminal‐mediated neuropathic pain. Nerve injury reduces ZBTB18 in trigeminal ganglion neurons, impairing CHD4/NuRD recruitment and de‐repressing Clic1. Elevated CLIC1 enhances chloride channel activity and neuronal hyperexcitability, thereby driving pain.
Shoupeng Wang   +11 more
wiley   +1 more source

Unravelling the Distinct Phenotype and Mechanosensitive Properties of Different Tendon Cell Populations

open access: yesAdvanced Science, EarlyView.
Tendon interfascicular and fascicular matrix cells are isolated and cultured, revealing distinct phenotypes and mechanosensitive responses. Interfascicular matrix cells exhibit marked stiffness‐dependent phenotypic plasticity, whereas fascicular matrix cells remain comparatively stable.
S. E. Grossemy   +10 more
wiley   +1 more source

ACSL4‐Dependent Lysosomal Lipid Peroxidation Links WTAP‐Mediated m6A Modification to Intervertebral Disc Degeneration

open access: yesAdvanced Science, EarlyView.
IL‐1β upregulates the protein level of WTAP, which promotes the m6A modification of ACSL4 mRNA in an IGF2BP2‐dependent manner, thereby enhancing its stability. The increased ACSL4 drives lipid peroxidation, leading to lysosomal membrane permeabilization (LMP) and impaired mitophagy, which collectively accelerate intervertebral disc degeneration (IVDD).
Shu Jia   +8 more
wiley   +1 more source

Impaired Chaperone‐Mediated Autophagy Accelerates Intervertebral Disc Degeneration by Inducing MIDN Accumulation to Target TSC2 for Proteasomal Degradation

open access: yesAdvanced Science, EarlyView.
This graphical abstract illustrates how chaperone‐mediated autophagy (CMA) regulates intervertebral disc degeneration (IDD). Under normal homeostasis (B), CMA degrades cytoplasmic Midnolin (MIDN) to maintain proteostasis. Under inflammatory stress (A), impaired CMA leads to cytoplasmic MIDN accumulation.
Xianglong Chen   +9 more
wiley   +1 more source

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