Results 181 to 190 of about 643,488 (262)

cis‐Carboxylate Enhancement of Mn(III)‐OH Hydrogen Atom Abstraction through PCET Thermodynamics

open access: yesAdvanced Science, EarlyView.
ABSTRACT Manganese(III)‐hydroxo intermediates are proposed as key hydrogen atom abstraction (HAA) species in manganese‐dependent enzymes, yet how first‐sphere carboxylate ligands control their proton‐coupled electron transfer (PCET) thermodynamics remains poorly understood.
Yuri Lee   +4 more
wiley   +1 more source

SCTR–Expressing Astrocyte–Serotonergic Neuron Signaling Drives Sexual Dimorphism in Depression Through KAT7/H4ac–Foxc2 Epigenetic Axis in an AMPK‐Dependent Manner

open access: yesAdvanced Science, EarlyView.
Astrocytic SCTR modulates depressive‐related phenotypes via AMPKα1, whereas lowered Mt1 blunts Megalin‐dependent AMPKα2 signaling in serotonergic neurons. Diminished AMPKα2 hinders KAT7 nuclear translocation, curtails KAT7 occupancy and H4K8ac at the Foxc2 promoter, and represses Foxc2 transcription, revealing cell‐type‐specific AMPK‐linked epigenetic ...
Fantao Meng   +15 more
wiley   +1 more source

Neonatal Sevoflurane Exposure Induces Long‐Term Cognitive Impairment via Epigenetically Mediated MMP9 Activation and Perineuronal Net Disruption in the Hippocampal CA2

open access: yesAdvanced Science, EarlyView.
Hippocampal CA2 perineuronal nets ensheathing excitatory pyramidal neurons are selectively vulnerable to repeated neonatal sevoflurane exposure. Epigenetic upregulation of MMP9 via reduced H3K27me3 disrupts PNN integrity, impairs BDNF–TrkB signaling, and causes synaptic protein loss and dendritic spine deficits, leading to persistent social and spatial
Lirong Liang   +11 more
wiley   +1 more source

Developmentally Guided Differentiation of Ventral Midbrain Dopaminergic Cells Validated in Proteopathy‐Based Parkinson's Disease Models

open access: yesAdvanced Science, EarlyView.
A developmentally guided protocol reproducibly specifies EN1‐positive ventral midbrain dopaminergic (vmDA) progenitors from human pluripotent stem cells and yields functional vmDA neurons. Optogenetic induction of α‐synuclein aggregation elicits selective degeneration of TH‐positive neurons in 2D cultures and 3D neurospheroids, while transplanted ...
Heechang Moon   +12 more
wiley   +1 more source

Huntingtin Aggregate‐Responsive Autophagy Gene Circuit Mitigates Disease Pathology in R6/2 Mice

open access: yesAdvanced Science, EarlyView.
CD98‐mediated receptor‐mediated transcytosis enables LIP‐CD98 nanocarriers to cross the blood–brain barrier and deliver ARAA to neurons. mHTT aggregates activate the 11G–NarX sensor, initiating Auto‐P and Trans‐P signaling through the VP48–NarL relay.
Jie Zhu   +8 more
wiley   +1 more source

Sarbecoviruses Suppress Innate Immunity by Recruiting PPM1A to Modulate STAT2 and ORF9b Phosphorylation

open access: yesAdvanced Science, EarlyView.
Sarbecovirus ORF9b recruits host phosphatase PPM1A to suppress innate immunity through dual mechanisms. PPM1A directly dephosphorylates ORF9b to sustain its activity and indirectly downregulates STAT2 phosphorylation to impair interferon signaling. Pharmacological inhibition of PPM1A restores antiviral responses and limits sarbecovirus replication ...
Lixiang Xie   +24 more
wiley   +1 more source

Drug Repurposing for Treating NCOR‐Related Intellectual Disability

open access: yesAdvanced Science, EarlyView.
An autism‐associated NCOR1 heterozygous mutation upregulates NRGs and activates NRG backward signaling in hypothalamic GABAergic neurons in mouse models, leading to Gabra2 downregulation and cognitive deficits, which can be therapeutically targeted by repurposing FDA‐approved drugs.
Yan Kong   +15 more
wiley   +1 more source

In Situ Photo‑Crosslinked Functional Bilayer Hydrogel Modulates Local Microenvironment and Remyelination After Optic Nerve Injury

open access: yesAdvanced Science, EarlyView.
A blue‐light‐crosslinked bilayer hydrogel was developed for local optic nerve repair. The adhesive GM‐Odex outer layer seals and anchors the lesion, while the non‐adhesive GM‐imid inner layer releases MPDA‐Cle without obstructing CSF flow. This system modulates oxidative and inflammatory microenvironments, supports oligodendrocyte differentiation and ...
Tonghe Pan   +13 more
wiley   +1 more source

NCOA4 Accelerates Abdominal Aortic Aneurysm Formation by Regulating Macrophage Activation and Ferroptosis via STAT1–CH25H Axis

open access: yesAdvanced Science, EarlyView.
Under pathological stimulation, NCOA4 in macrophages interacts with STAT1 to promote CH25H transcription. The subsequent increase in 25‐HC production activates macrophages, triggers inflammatory responses and ferroptosis, and accelerates the progression of AAA.
Zhinan Wu   +9 more
wiley   +1 more source

EphB1 Receptor Blockade Augments Morphine Antinociception via Inhibiting GRK2‐Mediated µ‐Opioid Receptor Internalization

open access: yesAdvanced Science, EarlyView.
Administration of opioids activates ephrinB2‐EphB1 receptor signaling. Activated EphB1 receptors induce GRK2‐mediated phosphorylation of MOR at Ser375, which initiates the internalization of MOR and reduces opioid antinociception at the behavioral level. ABSTRACT Opioids are the primary treatment for severe pain in clinical practice.
Bo Peng   +7 more
wiley   +1 more source

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