Results 111 to 120 of about 95,130 (254)

Pathogen‐Centric Activation of an Azoreductase‐Responsive Antibody‐Antibiotic Conjugate for the Targeted Eradication of MRSA

open access: yesAdvanced Science, EarlyView.
A pathogen‐centric antibody‐antibiotic conjugate (AZO‐AAC) releases antibiotics via bacterial azoreductase, independent of host‐lysosomal function. This mechanism achieves nanomolar eradication of both planktonic and intracellular methicillin‐resistant Staphylococcus aureus (MRSA).
Qi Cheng   +13 more
wiley   +1 more source

CK2α Deficiency Drives Myocardial Fibrosis via Desmin‐Induced Mitochondrial Dysfunction

open access: yesAdvanced Science, EarlyView.
CK2α preserves mitochondrial homeostasis by phosphorylating Desmin to recruit Cryab, ensuring proper filament assembly. CK2α deficiency disrupts this interaction, causing mitochondrial dysfunction, metabolic shifts, bioenergetic failure, and oxidative stress—ultimately establishing a pro‐fibrotic environment that drives cardiac fibrosis.
Canjie Ma   +12 more
wiley   +1 more source

ZDHHC18‐Mediated Palmitoylation of ORF3a Promotes SARS‐CoV‐2 Pathogenesis by Antagonizing TRIM16‐Mediated Ubiquitination and Proteasomal Degradation

open access: yesAdvanced Science, EarlyView.
Palmitoylation by ZDHHC18 blocks ORF3a K27‐linked ubiquitination mediated by TRIM16, thereby preventing its proteasomal degradation and strengthening viral pathogenesis. Targeting palmitoylation through a pharmacological inhibitor (2‐BP), a competitive inhibitory peptide (OPIP), or adenovirus‐mediated knockdown of ZDHHC18 expression presents a ...
Sidi Yang   +17 more
wiley   +1 more source

Stage‐Specific H3K14 and H3K23 Succinylation Orchestrates Insect Metamorphosis and Oogenesis

open access: yesAdvanced Science, EarlyView.
Stage‐specific succinylation of histone H3 at lysine 14 and 23 differentially controls insect metamorphosis and oogenesis through distinct GPCR‐PKC signaling cascades, revealing an evolutionarily conserved epigenetic mechanism that coordinates key life‐history traits.
Yu‐Pu Jing   +9 more
wiley   +1 more source

ZDHHC17‐Mediated CDK4 Palmitoylation Drives Cell Cycle Progression and Orchestrates Cancer Immune Surveillance

open access: yesAdvanced Science, EarlyView.
ZDHHC17 palmitoylates CDK4, which together with TRAF6‐mediated ubiquitination, drives cell cycle progression and immune surveillance, revealing a rational combination of CDK4 inhibitors with immune checkpoint blockers for ZDHHC17‐driven cancers. ABSTRACT Uncontrolled cell cycle progression is a hallmark of cancer, tightly regulated by both intrinsic ...
Zekang Wang   +7 more
wiley   +1 more source

ABHD17C‐Mediated S‐Depalmitoylation of BCL6B Enhances CD24 Transcription to Resist Macrophage Phagocytosis in Pancreatic Cancer

open access: yesAdvanced Science, EarlyView.
ABHD17C‐mediated depalmitoylation of BCL6B at Cys442 blocks its nuclear import and triggers ubiquitin‐dependent degradation, attenuating transcriptional repression of the anti‐phagocytic signal CD24. This mechanism enables pancreatic cancer cells to evade macrophage phagocytosis and fosters an immunosuppressive microenvironment.
Yalu Zhang   +9 more
wiley   +1 more source

IKKβ and USP28 Regulate HEY1 Stability to Promote Cancer Stemness and Immune Evasion in Hepatocellular Carcinoma

open access: yesAdvanced Science, EarlyView.
The uncovered IKKβ‐USP28‐HEY1 axis fuels cancer stemness and immune evasion in hepatocellular carcinoma. USP28 deubiquitinates HEY1 upon IKKβ‐mediated phosphorylation, conferring PD‐1/PD‐L1 blockade resistance. Pharmacological inhibition of USP28 sensitizes resistant tumors to anti‐PD‐1 immunotherapy, revealing a promising therapeutic strategy ...
Na Shao   +8 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

PhosSight: A Unified Deep Learning Framework Boosting and Accelerating Phosphoproteome Identification to Enable Biological Discoveries

open access: yesAdvanced Science, EarlyView.
PhosSight is a unified deep‐learning framework for phosphoproteome identification, featured by a phosphorylation‐aware detectability predictor. It improves identification sensitivity in DDA through deep re‐localization and rescoring, accelerates DIA searches by detectability‐guided spectral library pruning, and expands phosphoproteome coverage to ...
Ben Wang   +10 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

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