Results 181 to 190 of about 3,948,731 (294)

Single‐Cell Transcriptomic Profiling Identifies B Cell‐Intrinsic Dysregulation of Sphingolipid Biosynthesis and Could Be Improved by Inhibiting UGCG in Primary Immune Thrombocytopenia

open access: yesAdvanced Science, EarlyView.
This study generates the single‐cell atlas of pathogenic B‐cell subset Bc‐5 in ITP. It identifies RUNX3 as a key survival regulator and uncovers sphingolipid‐driven metabolic reprogramming, validating UGCG inhibition as a therapeutic candidate and building a valuable resource for ITP mechanistic and therapeutic exploration.
Dongmei Luo   +10 more
wiley   +1 more source

Galactokinase 1 Positively Regulates Mitochondrial Respiration by Phosphorylating TIMM13 as a Protein Kinase

open access: yesAdvanced Science, EarlyView.
GALK1 acts as a protein kinase beyond the phosphorylation of galactose. GALK1 phosphorylates TIMM13 at Y73 in the cytoplasm. This phosphorylation prevents premature oxidative folding of TIMM13 and ensures its entrance into the intermembrane space of mitochondrion, positively regulating mitochondrial respiration.
Chang Woo Ko   +5 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

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

Long‐Term Human Skin Platform for Modeling Chronic Inflammation, Environmental Stress, and Therapeutic Intervention

open access: yesAdvanced Science, EarlyView.
An advanced, long‐term human skin platform maintains native skin structure and key tissue functions for up to four weeks. The platform models chronic inflammation, aging‐related skin changes, and UVB damage, enabling drug and topical interventions—including anti‐inflammatory therapy, senolytic treatment, and sunscreen—to be evaluated in intact human ...
Purnendu Kumar Sharma   +14 more
wiley   +1 more source

Metabolic Signatures for Liver Cancer Diagnosis and Mechanistic Insights: A Large‐Scale, Multicenter Study

open access: yesAdvanced Science, EarlyView.
A large‐scale multicenter serum metabolomics study (13 centers, n = 2,149) identified a 9‐metabolite + AFP diagnostic signature for liver cancer (AUC = 0.93). Among the signature, nicotinamide (NAM) was validated as an oncometabolite: NAM enhances NAD+ synthesis, activating SIRT1 to deacetylate and stabilize HIF1α, thereby driving glycolysis, MAPK ...
Yongjie Xu   +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

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