Results 81 to 90 of about 996,236 (307)

Phosphorylation‐Facilitated CKB Lactylation At K11 By GCN5 Enhances Creatine Kinase Activity and Mitigates Neuronal Damage After Cerebral Ischemia‐Reperfusion

open access: yesAdvanced Science, EarlyView.
This study uncovers hierarchical coordination between K11 lactylation and S199 phosphorylation of CKB in cerebral ischemia‐reperfusion injury. Such dual modifications potentiate CKB enzymatic function, remodel energy metabolism, alleviate oxidative stress and neuronal damage, and represent a viable therapeutic target for stroke treatment.
Chao Duan   +17 more
wiley   +1 more source

β‐Elemene Rescues Radiation‐Induced Enteritis by Orchestrating a Host‐Microbiome Circuit That Fuels Epigenetic DNA Repair

open access: yesAdvanced Science, EarlyView.
This study elucidates that β‐elemene promotes cellular uptake of L. gasseri‐derived lactate by enhancing the membrane translocation of MCT1 in a CD147‐dependent manner. Intracellular lactate, through the lactylation of RBBP4 at the K26 site, recruits EP300 to the promoter regions of downstream genes (POLD1/POLD3), catalyzing H3K27ac modification.
Jiancheng He   +10 more
wiley   +1 more source

A Non‐Canonical Role of SMAD4 in Regulating 3D Genome Architecture to Inhibit Lung Squamous Cell Carcinoma Development

open access: yesAdvanced Science, EarlyView.
SMAD4 is identified as a guardian of 3D genome architecture in lung squamous cell carcinoma. Loss of SMAD4 unleashes EP300 at chromatin loop anchors, strengthening enhancer–promoter looping and H3K27ac at the SOX2 locus to drive aberrant SOX2 activation and tumor cell proliferation.
Qian Tang   +33 more
wiley   +1 more source

mTORC2 Phosphorylation of GSDME‐N Drives Cullin4B‐Mediated Proteasomal Degradation to Suppress Pyroptosis and Confer Radioresistance in Small Cell Lung Cancer

open access: yesAdvanced Science, EarlyView.
Radioresistance severely limits the efficacy of therapies for small cell lung cancer (SCLC). This study reveals a novel mechanism of resistance driven by the active suppression of pyroptosis. Specifically, the mTORC2 complex directly phosphorylates GSDME‐N and promotes its CUL4B‐mediated ubiquitination and proteasomal degradation.
Qing‐qing Xu   +11 more
wiley   +1 more source

Single‐Cell Annotation and Localization via Integrating Spatial Transcriptomics Maps the Mouse Ocular Atlas and RAO Dynamics

open access: yesAdvanced Science, EarlyView.
We developed the ASCAL pipeline, integrating complementary spatial transcriptomics, to construct a high‐fidelity mouse whole‐eye single‐cell atlas. Applying ASCAL to a retinal artery occlusion (RAO) model revealed spatially restricted immune activation localized to the ganglion cell layer and the selective depletion of a translationally active, outer ...
Chen Du   +11 more
wiley   +1 more source

SuFEx‐Enabled Reprogramming of Flavonoids for Selective α‐Glucosidase Covalent Inhibition

open access: yesAdvanced Science, EarlyView.
Selective inhibition of intestinal α‐glucosidase remains limited by poor enzyme specificity and off‐target metabolic effects. Here, SuFEx click chemistry is used to reprogram natural flavonoids into covalent inhibitors with enhanced α‐glucosidase selectivity and controlled reactivity. This strategy enables effective regulation of carbohydrate digestion
Fengyu Guo   +14 more
wiley   +1 more source

CEBPG‐Mediated Palmitic Acid Adaptation of Cancer‐Associated Fibroblasts Drives Metastasis of Oral Squamous Cell Carcinoma

open access: yesAdvanced Science, EarlyView.
This study reveals a metabolic signaling axis in the OSCC microenvironment where palmitic acid (PA) drives the activation of CAFs. PA uptake triggers CEBPG‐dependent epigenetic remodeling to upregulate ERN1 and TMBIM6, thereby mitigating ER stress. This adaptive program sustains CAF survival and the pro‐metastatic phenotype, establishing this pathway ...
Yiling Duan   +6 more
wiley   +1 more source

Engineered Exosomal miR‐146a‐5p Reprograms BMSC Fate and Restores Mitochondrial Homeostasis in Glucocorticoid‐Induced Osteonecrosis of Femoral Head

open access: yesAdvanced Science, EarlyView.
Exosomal miR‐146a‐5p is identified as a pivotal regulator in steroid‐induced osteonecrosis. Its reduction activates NF‐κB signaling, compromises mitophagy, and disrupts mitochondrial bioenergetics, resulting in autophagic disequilibrium. Engineered exosomes delivering miR‐146a‐5p reinstate mitochondrial function, augment oxidative phosphorylation and ...
Zehui Lv   +13 more
wiley   +1 more source

Epidermal METTL1‐Mediated m7G Modification Drives Psoriatic Inflammation by Stabilizing Bdkrb1 and Orchestrating Neutrophil Recruitment

open access: yesAdvanced Science, EarlyView.
This study unveils an unrecognized pro‐inflammatory epitranscriptomic checkpoint in psoriasis. By installing m7G modifications on the 5′ UTR of Bdkrb1 mRNA, METTL1 enhances receptor stability to orchestrate keratinocyte‐driven neutrophil recruitment via p38 MAPK signaling.
Chang Zhang   +10 more
wiley   +1 more source

Lesion Site‐Targeted Microspheres Modulate Nav1.7‐Related Signaling for Osteoarthritis Treatment

open access: yesAdvanced Science, EarlyView.
Cartilage‐targeted carbamazepine‐loaded WYRGRL‐modified composite microspheres (CBZ/WCOM) anchor to exposed type II collagen in osteoarthritic lesions and release carbamazepine under acidic conditions. This bind‐then‐release platform modulates Nav1.7‐related sodium signaling, Na⁺/Ca²⁺ exchanger‐associated Ca2+ dynamics, and heat shock protein 70 ...
Cheng Chen   +15 more
wiley   +1 more source

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