Results 91 to 100 of about 53,996 (252)

Enhanced Glycolysis‐Driven Histone H3K18 Lactylation Regulates Epileptogenesis by Modulating the E3 Ubiquitin Ligase COP1

open access: yesAdvanced Science, EarlyView.
Neuronal PKM2‐driven glycolysis generates excess lactate that triggers histone H3K18 lactylation (H3K18la), establishing a pathogenic metabolic‐epigenetic axis in epilepsy. Elevated H3K18la enriches the Cop1 promoter, transcriptionally upregulating the E3 ubiquitin ligase COP1, which subsequently drives proteasomal degradation of GABAARβ2 and impairs ...
Yuan Meng   +8 more
wiley   +1 more source

Nigra‐Subthalamic Dopaminergic Circuitry Modulates and Represents Distinct Pain Modality in Physiological and Pain States in Mice

open access: yesAdvanced Science, EarlyView.
Nigral dopaminergic (DA) neurons modulate and represent pain with a preference to a particular modality (mechanical) and laterality (contralateral), which are controlled by nigral GABAergic neurons. The pain modulation is mimicked by the nigro‐subthalamic projection and its downstream neurons, involving D2‐like receptors.
Ying Ji   +13 more
wiley   +1 more source

FGF13 Deficiency Ameliorates Paclitaxel‐Induced Neuropathic Pain by Inhibiting VASH1‐Mediated Microtubule Detyrosination to Promote Mitophagy

open access: yesAdvanced Science, EarlyView.
FGF13 is upregulated in DRG neurons of PIPNP model mice. DRG neuron‐specific knockout of FGF13 ameliorates PIPNP symptoms. Mechanistically, FGF13 potentiates microtubule detyrosination by promoting VASH1 binding to microtubules. FGF13 knockout suppresses VASH1‐mediated microtubule detyrosination and promotes α‐tubulin tyrosination.
Yiming Dong   +10 more
wiley   +1 more source

Endoplasmic Reticulum Geometry Dictates Neuronal Bursting via Calcium Store Refill Rates and Exposes Selective Neuronal Vulnerability

open access: yesAdvanced Science, EarlyView.
The ER's continuous tubular network is maintained by ER‐shaping proteins whose mutation or dysregulation contributes to neurodegenerative diseases. Here, we show that ER morphology sets the speed of Ca2+ store replenishment between firing events. Disrupting ER continuity slows intra‐ER Ca2+ redistribution from extracellular refill (SOCE) sites, driving
Valentina Davi   +13 more
wiley   +1 more source

Targeting Supramolecular Active Complexes of Nav1.7/Nav1.8 to Relieve Chronic Neuropathic Pain

open access: yesAdvanced Science, EarlyView.
In mice and patients with severe chronic neuropathic pain (NP), Nav1.7, Nav1.8, TrkB, and five cytoskeletal proteins form supramolecular active complexes (SMACs) with polygonal lattice structures as noxious signal amplifiers in dorsal root ganglion (DRG) neurons.
Liting Sun   +27 more
wiley   +1 more source

Engineering Approaches to Modify Immunomodulatory Functions of Mesenchymal Stromal Cells (MSCs): Tissue Regeneration and Clinical Application

open access: yesAdvanced Science, EarlyView.
Mesenchymal stromal cells (MSCs) show promise for treating immune‐related disorders through immunomodulation and tissue regeneration. This review gives a brief overview of current clinical approval of MSC therapies. It also discussed how bioengineering, including genetic modification, biomaterial delivery, extracellular vesicles, and iPSC‐derived MSCs,
Sichen Yang   +6 more
wiley   +1 more source

ANKS1B in the Nucleus Accumbens Controls Escalated Cocaine Self‐Administration via Regulating CBP‐FoxO3 Complex

open access: yesAdvanced Science, EarlyView.
ANKS1B in the nucleus accumbens plays a critical role in the transition from controlled to escalated cocaine intake. Mechanistically, ANKS1B interacts with CBP to epigenetically suppress FoxO3 through H3K27 acetylation. The ANKS1B‐CBP‐FoxO3 signaling cascade presents a novel theraputic target for the treatment of cocaine addiction.
Liping Yang   +15 more
wiley   +1 more source

Astrocytic Phenotypic Switching in Posterior Piriform Cortex Orchestrates Bone Cancer Pain–Depression Comorbidity via Purinergic–Noradrenergic Signaling

open access: yesAdvanced Science, EarlyView.
Bone cancer pain and depression share a common origin: astrocytic A2‐to‐A1 transition in the posterior piriform cortex. This phenotypic shift disrupts the ATP–adenosine–A2AR–norepinephrine axis, simultaneously driving nociceptive and affective dysfunction.
Jiang‐Ping Liu   +14 more
wiley   +1 more source

Cross‐Modal Denoising and Integration of Spatial Multi‐Omics Data with CANDIES

open access: yesAdvanced Science, EarlyView.
In this paper, we introduce CANDIES, which leverages a conditional diffusion model and contrastive learning to effectively denoise and integrate spatial multi‐omics data. We conduct extensive evaluations on diverse synthetic and real datasets, CANDIES shows superior performance on various downstream tasks, including denoising, spatial domain ...
Ye Liu   +5 more
wiley   +1 more source

Endogenous Engineering Reprograms Extracellular Vesicles for Enhanced Therapeutic Function

open access: yesAdvanced Science, EarlyView.
This review explains how Extracellular vesicles‐producing cells can be endogenously engineered to load therapeutic proteins and nucleic acids. We summarize physiological and genetic strategies that harness native sorting pathways for selective cargo loading.
Jinghui Wang   +10 more
wiley   +1 more source

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