Results 181 to 190 of about 4,392 (256)

Allosteric Inhibition of Polycomb Repressive Complex 2 by an EZH2‐Selective Small Molecule Inhibitor

open access: yesAdvanced Science, EarlyView.
The study characterizes C36, a highly selective EZH2/PRC2 inhibitor that acts via a novel allosteric mechanism. Unlike previous inhibitors, C36 inhibits EZH2/PRC2 by disrupting the allosteric communication between EZH2 and EED in a SAM‐noncompetitive manner.
Ting Cao   +11 more
wiley   +1 more source

Pemt Inhibition‐Mediated Vdac1 Oligomerization Regulates Mitochondrial Dysfunction, Apoptosis, and Inflammation in High‐Fat Diet‐Derived Liver Injury

open access: yesAdvanced Science, EarlyView.
ABSTRACT High‐fat diet (HFD)‐induced hepatic injury represents a pathology observed across vertebrates, yet the underlying mechanisms remain incompletely understood. Herein, the present study identifies phosphatidylethanolamine methyltransferase (Pemt), a key enzyme in phosphatidylcholine synthesis, as a critical regulator of mitochondrial homeostasis ...
Xianyong Bu   +11 more
wiley   +1 more source

The E3 Ligase RNF115 Aggravates Pathological Cardiac Hypertrophy via Ubiquitin‐Mediated Degradation of SPTBN1

open access: yesAdvanced Science, EarlyView.
In response to hypertrophic stimuli, increased c‑JUN phosphorylation upregulates RNF115, leading to SPTBN1 ubiquitination and degradation. which promotes F‑actin depolymerization and YAP activation, driving cardiac hypertrophy. The RNF115 inhibitor DTD effectively suppresses SPTBN1 ubiquitination and cardiac hypertrophy.
Yan Zu   +12 more
wiley   +1 more source

Single‐Cell Reveal GALNT7‐Dependent Ferroptosis Suppression as a Mechanism of Immunotherapy Resistance in Non‐Small Cell Lung Cancer

open access: yesAdvanced Science, EarlyView.
Integrated clinical and mechanistic analyses identify GALNT7 as a ferroptosis‐suppressive regulator associated with immunotherapy resistance in non‐small cell lung cancer. GALNT7 depletion promotes lipid peroxidation, mitochondrial dysfunction, and ferroptosis, enhances CD8+ T‐cell activation and IFN‐γ production, and sensitizes tumors to PD‐1 blockade,
Jiadi Gan   +11 more
wiley   +1 more source

Astrocytic FDX1 Contributes to Copper Dyshomeostasis‐associated Synaptic Dysfunction in Depression and Is Modulated by Exercise

open access: yesAdvanced Science, EarlyView.
Chronic stress disrupts copper homeostasis and promotes copper accumulation in the prelimbic cortex, leading to astrocytic FDX1 upregulation. Elevated astrocytic FDX1 impairs calcium signaling, induces structural atrophy, and disrupts synaptic function, contributing to depressive‐like behaviors. Physical exercise reverses these alterations by restoring
Lina Gao   +11 more
wiley   +1 more source

Mechanical Activation of Piezo1 Drives Osteoarthritis Through Kdm5c‐Mediated Epigenetic Silencing

open access: yesAdvanced Science, EarlyView.
Excessive mechanical stress activates Piezo1, triggering Ca2+‐dependent cytoskeletal forces that deform the nucleus and reduce H3K4me3. Kdm5c demethylates H3K4me3 at Col2a1 and Runx3 promoters. Kdm5c knockout rescues degradation. Repurposed telmisartan directly inhibits Kdm5c, blocking this axis and showing disease‐modifying efficacy in mouse OA models
Tianyou Kan   +13 more
wiley   +1 more source

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