Results 151 to 160 of about 438,461 (269)

Targeting the PDK1/c‐Myc/SOX10 Signaling in Oligodendrocytes Alleviates Neuropathic Pain

open access: yesAdvanced Science, EarlyView.
This work reveals that oligodendrocyte homeostasis, mediated by PDK1, is a critical determinant of neuropathic pain (NPP) pathogenesis. Disruption of PDK1 in oligodendrocytes impairs SOX10‐dependent myelination programs through c‐Myc accumulation, leading to disrupted myelination and the pathophysiology of NPP.
Pingping Qiao   +7 more
wiley   +1 more source

PRMT1‐Mediated LDHA Methylation Drives STAT3 Lactylation to Orchestrate Intestinal Inflammation and Tumorigenesis

open access: yesAdvanced Science, EarlyView.
This study identifies an immunometabolic axis wherein SAM‐driven PRMT1 methylates LDHA, enhancing its activity. The resultant lactate induces STAT3 K709 lactylation, which stabilizes an active conformation to promote STAT3 phosphorylation and IL‐10 expression.
Hui Wang   +12 more
wiley   +1 more source

Protein Disulfide Isomerase Disassembles TDP‐43/G3BP1 Condensates and Antagonizes TDP‐43 Pathological Aggregates

open access: yesAdvanced Science, EarlyView.
Cytoplasmic aggregation of TDP‐43 is a common pathological feature in amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and Alzheimer's disease with TDP‐43 pathology. This study reports that wild‐type PDI slows down phase separation of TDP‐43 through direct interaction with TDP‐43.
Jia‐Qi Liu   +14 more
wiley   +1 more source

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

A Radioresistant‐Tumor‐Targeted Nanoparticle for X‐Ray‐Controlled Nitric Oxide Release to Potentiate Radiotherapy

open access: yesAdvanced Science, EarlyView.
The PBTN targets GRP78 and, upon X‐ray irradiation, generates ONOO− to induce immunogenic cell death, thereby activating CD8+ T cells and establishing a systemic antitumor immune response. ABSTRACT Nitric oxide (NO) treated radioresistant tumors by relieving hypoxia and blocking DNA repair, but its nonselective toxicity has precluded therapeutic use ...
Wanze Zhang   +10 more
wiley   +1 more source

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