Results 201 to 210 of about 260,789 (262)

Natural Products Inspired Scaffold Diversification Leads to Unnatural Molecular Warhead and Covalent Strategy to Modulating Protein Function through Electrophilic Bromine Transfer

open access: yesAdvanced Science, EarlyView.
We report a new thiolate‐reactive α,α‐gem‐dibromo lactam warhead that activates transcription factor Nrf2 and demonstrates anti‐inflammatory activities, which have implications in cancer, neurodegeneration, and cardiovascular diseases. RNA‐seq illuminated detailed transcriptional profiles, and chemical reactions with cysteine‐containing compounds ...
Beau R. Brummel   +16 more
wiley   +1 more source

Genome‐Wide CRISPR Screen Identifies a microRNA Orchestrating Pleiotropic Resistance to Targeted Therapy and T Cell Immunity in Melanoma

open access: yesAdvanced Science, EarlyView.
A genome‐wide microRNA CRISPR screen identifies miR‐18a as a master regulator of cross‐resistance in melanoma. Loss of miR‐18a activates the AJUBA–YAP/Hippo axis to confer BRAFi resistance and enhances THBS1–CD47 interaction to impair CD8+ T cell immunity. hnRNP A1 is identified as an upstream regulator of miR‐18a processing.
Zhao Wang   +19 more
wiley   +1 more source

Adipocyte‐Derived Leptolin Enhances Energy Expenditure and Prevents Obesity

open access: yesAdvanced Science, EarlyView.
We identified a novel adipokine, which we named leptolin. In humans, leptolin levels in white adipose tissue were positively correlated with exercise and negatively associated with body mass index. We observed elevated leptolin in serum from athletes and lower leptolin in serum from obese individuals.
Jiarui Liu   +17 more
wiley   +1 more source

Agnuside Stabilizes the Complex I Assembly Factor NDUFAF6 to Reinforce Mitochondrial Efficiency and Thermogenic Responsiveness

open access: yesAdvanced Science, EarlyView.
ABSTRACT Brown and beige adipocytes dissipate energy as heat, yet effective strategies to enhance their mitochondrial efficiency remain limited. Here, we identify Agnuside (AGN) as a selective stabilizer of the complex I assembly factor NDUFAF6. AGN directly binds cytosolic NDUFAF6, suppresses its ubiquitination, prolongs its half‐life, and facilitates
Qingwen Zhao   +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

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

Heme‐NO Dilates Arteries via Mobilization of NO Moieties From an Intracellular NO Store Within Vascular Smooth Muscle Cells

open access: yesAdvanced Science, EarlyView.
Nitrosyl heme emerges as an extracellular nitrodilator that dilates arteries without crossing the cell membrane. Instead, heme‐NO mobilizes NO moieties from a preformed intracellular NO store within vascular smooth muscle, providing both functional and chemical evidence for the NANOS model, revealing a previously unrecognized mechanism of arterial ...
Taiming Liu   +9 more
wiley   +1 more source

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