Results 161 to 170 of about 530,869 (198)

TECTB Variants Reveal Tectorial Membrane Vulnerability in Dominant Non‐Syndromic Hearing Loss

open access: yesAdvanced Science, EarlyView.
TECTB is a non‐collagenous protein of the tectorial membrane – an extracellular matrix of the cochlea. This study identifies dominant missense variants in TECTB linked to human hereditary deafness in two unrelated families. Genetically engineered mice homozygous for one of the variants are profoundly deaf, whereas heterozygous mice have normal hearing ...
Evan B. Hale   +23 more
wiley   +1 more source

Probing the Energy Landscape of α‐Synuclein Amyloid Fibril Formation by Systematic K‐to‐Q Mutagenesis

open access: yesAdvanced Science, EarlyView.
We use lysine‐to‐glutamine mutations to study the effect of electrostatics on the kinetics and thermodynamics of alpha‐synuclein amyloid fibril formation. We find that mutational effects map on their structural context within fibrils and identify residues that modulate the energy landscape of alpha‐synuclein self‐assembly. Our work outlines a scalable,
Antonin Kunka   +10 more
wiley   +1 more source

Supramolecular Zinc–Polyphenol Coordination Assemblies Mitigate Colonic Inflammation by Regulating Mucosal Barrier and Microbiome

open access: yesAdvanced Science, EarlyView.
A carrier‐free zinc‐coordinated polyphenol nanoplatform (ZnCA NPs) is designed as an “all‐in‐one” therapeutic strategy for intestinal inflammation. The ZnCA NPs exhibit enhanced colonic accumulation and broad‐spectrum reactive oxygen and nitrogen species scavenging.
Qiwen Xie   +7 more
wiley   +1 more source

Reversible, Chemically Gated FRET via Ligand‐Activated Acceptors

open access: yesAdvanced Science, EarlyView.
Fluorogen binding turns the compact FAST tag into a tunable FRET acceptor, with ligand chemistry programming spectral overlap and excited‐state lifetimes. Fluorescence‐lifetime imaging reads out energy transfer through the shortened donor lifetime, while simply adding or washing out the dye switches FRET on and off, reversibly mapping the supramodular ...
Nivedita Singh   +7 more
wiley   +1 more source

Macrophage Dab1 Links Early Hypoxia to Adaptive Angiogenesis to Drive Peripheral Nerve Repair

open access: yesAdvanced Science, EarlyView.
Schematic diagram illustrating the Dab1‐linked hypoxia signaling pathway that accelerates angiogenesis and consequent nerve regeneration. Following PNI, a hypoxic microenvironment develops. Hypoxia induces macrophage Dab1 phosphorylation, resulting in NHE‐1 upregulation, HIF‐1α stabilization, and VEGF‐A expression. This cascade promotes angiogenesis in
Xiongyao Zhou   +14 more
wiley   +1 more source

Matrix Rigidity Mechanoprimes Microglia for Inflammation Through Cytoskeletal‐to‐Nuclear Signaling and 3D Spatio‐Epigenomic Remodeling

open access: yesAdvanced Science, EarlyView.
Pathological tissue rigidity mechanoprimes microglia by enhancing actin cytoskeleton–nucleus coupling and chromatin opening at rigidity‐responsive cis‐regulatory elements (mechanoCREs). Subsequent NF‐κB/p65 signaling converges on this permissive regulatory state to amplify inflammatory gene expression and microglial activation.
Yu Xuan Meng   +15 more
wiley   +1 more source

Multi‐Tissue Crosstalk Regulating Meniscus Healing Under Inflammation and Physiological Loading

open access: yesAdvanced Science, EarlyView.
Using a novel Meniscus‐on‐a‐chip (MoC) model integrated with a meniscus‐specific bioreactor, this study investigated the roles of multi‐tissue crosstalk that regulates injury, healing, and degeneration of the meniscus injury under inflammation and pathophysiological loading.
Hun Jin Jeong   +5 more
wiley   +1 more source

An Extracellular Pore‑Targeting Peptide Defines a Designable Allosteric Site in TRPV2

open access: yesAdvanced Science, EarlyView.
Structure‐guided peptide engineering yields Depiv2, a highly potent and subtype‐selective TRPV2 inhibitor that binds to the extracellular pore and remodels it into a closed, non‐conductive state. Depiv2 suppresses pathological cardiac hypertrophy, establishing the TRPV2 outer pore as a designable interface for selective peptide modulation.
Aiqin Zhu   +7 more
wiley   +1 more source

Acid‐Responsive Nanobot‐Integrated Core‐Shell Microneedles Reprogram the Degenerative Annulus Fibrosus Microenvironment Through Epigenetic Suppression of Ferroptosis

open access: yesAdvanced Science, EarlyView.
An acid‐responsive core‐shell microneedle system normalizes the degenerative annulus fibrosus microenvironment by consuming pathological H+, generating O2, and providing NIR‐amplified redox buffering. Mechanistically, it epigenetically suppresses ferroptosis via DNMT3A‐dependent methylation of the ATF3 promoter, relieving ATF3‐mediated repression of ...
Lu Tan   +7 more
wiley   +1 more source

Persistent Zn2+ Influx‐Mediated Deacetylation of ANXA2 Regulates the “Zn2+‐Autophagic Flux” and Alleviates Intervertebral Disc Degeneration

open access: yesAdvanced Science, EarlyView.
Zinc transporter SLC39A14 sustains intracellular Zn2+ levels to activate SIRT3‑dependent ANXA2 deacetylation at K302. This modification weakens ANXA2‑mTOR binding and releases autophagic‑flux suppression in nucleus pulposus cells. Dysregulated Zn2+ homeostasis disrupts this axis to drive intervertebral disc degeneration.
Yuxin Jin   +23 more
wiley   +1 more source

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