Results 151 to 160 of about 694,984 (308)

Timing Mechanotransduction: Mechanically Dynamic Biomaterials Reveal the Temporal Hierarchy of YAP/TAZ Control Nodes

open access: yesAdvanced Science, EarlyView.
This work develops dynamically softening polyacrylamide hydrogels for time‐resolved imaging during continuous mechanical transitions. The study revealed that mechanotransduction is biphasic; YAP/TAZ inactivation is driven by early loss of the nucleocytoskeletal continuum connecting subnuclear adhesions, F‐actin, and the nuclear envelope, coupled with ...
Alessandro Gandin   +12 more
wiley   +1 more source

Hepatocyte PIEZO1 Negatively Regulates Lipogenesis and Ameliorates MASLD by Sensing Membrane Tension and Activating AMPK

open access: yesAdvanced Science, EarlyView.
Hepatocytes are subjected to increased membrane tension along with lipid accumulation. Loss of PIEZO1 exacerbates high‐fat diet‐induced MASLD in mice. Activation of PIEZO1 alleviates high‐fat diet‐induced MASLD in mice. PIEZO1 negatively regulates de novo lipogenesis through activation of CaMKK2‐AMPK pathway. ABSTRACT Liver is a central organ for lipid
Hui Chen   +14 more
wiley   +1 more source

A Tac1‐Expressing Brainstem Pathway Underlies the Pathogenesis of Trigeminal Neuralgia

open access: yesAdvanced Science, EarlyView.
A critical TG‐Sp5CTac1‐PBNTac1 pathway drives trigeminal neuropathic pain (TNP). Tac1‐expressing parabrachial nucleus (PBNTac1) neurons exhibit heightened responses to innocuous stimuli in TNP, and chemogenetic inhibition of these neurons effectively prevents TNP development.
Liting Sun   +11 more
wiley   +1 more source

Sphingomonas paucimobilis‐Driven Epithelial–Endothelial Transition in Adenomyosis Pathogenesis

open access: yesAdvanced Science, EarlyView.
This study identifies epithelial–endothelial transition (EET) as a novel adenomyosis pathogenic mechanism driven by Sphingomonas paucimobilis colonization. Systematic inhibitor experiments validate a TNFα→NF‐κB→MMP signaling cascade essential for EET. Critically, bacterial culture supernatant fails to induce pathological changes, demonstrating viable ...
Peigen Chen   +7 more
wiley   +1 more source

Cryo‐EM Structure Guided Engineering of Botulinum Neurotoxin A With Advanced Receptor Binding Affinity and Therapeutical Benefits

open access: yesAdvanced Science, EarlyView.
The butterfly unfolded wing in an open form structure of botulinum neurotoxin type A (BoNT/A) at physiological‐state was confirmed at 2.85 Å resolution by cryo‐electron microscopy (cryo‐EM). Structure‐guided protein engineering significantly enhanced the receptor‐binding affinity, therapeutic efficacy, and safety of the engineered toxin variants ...
Wenrui Wang   +16 more
wiley   +1 more source

ZDHHC9‐Mediated Palmitoylation of ACSL4 Drives Ferroptosis in Diabetes Mellitus–Induced Erectile Dysfunction

open access: yesAdvanced Science, EarlyView.
ABSTRACT Diabetes mellitus‐induced erectile dysfunction (DMED) is a highly prevalent complication among diabetic patients; however, its underlying pathogenic mechanisms remain incompletely understood. Metabolic disorder is a hallmark of diabetes, yet its precise contribution to DMED progression is not well defined.
Wanyang Guo   +14 more
wiley   +1 more source

ECM‐Stiffness Mediated Persistent Fibroblast Activation Requires Integrin and Formin Dependent Chromatin Remodeling

open access: yesAdvanced Science, EarlyView.
Prolonged exposure to stiff extracellular matrix drives cancer‐associated fibroblasts into a persistently activated myofibroblast state. Two parallel pathways are identified: β1 integrin activation smoothens the nuclear lamina to reduce lamin–chromatin contacts, while the formin mDia2 regulates nuclear actin to alter chromatin organization.
Swathi Packirisamy   +4 more
wiley   +1 more source

4‐Hydroxybenzyl Alcohol Mitigates Hyperlipidemia‐Associated Depression by Inhibiting Neuroinflammation via the NKIRAS2/NF‐κB Pathway

open access: yesAdvanced Science, EarlyView.
4‐HBA upregulates NKIRAS2 levels, inhibiting the activation of the NF‐κB pathway and subsequently reducing the levels of neuroinflammatory markers. This modulation helps restore normal mood and behavior in hyperlipidemic conditions, providing a potential therapeutic strategy for managing hyperlipidemia‐associated depression.
Ying Zhang   +7 more
wiley   +1 more source

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