Results 161 to 170 of about 1,093 (205)

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

LC3B Mediated SETDB1‐Accounted Alcoholic Steatohepatitis via Lipidation‐Dependent LAP and Lipidation‐Independent Nuclear Stabilization

open access: yesAdvanced Science, EarlyView.
SETDB1 is progressively downregulated in ALD, correlating with disease severity. SETDB1 deficiency impairs LAP by disrupting Rubicon membrane localization, leading to defective lipid droplet clearance. Concurrently, loss of SETDB1 reduces nuclear LC3B, causing R‐loop accumulation and cGAS‐STING‐driven inflammation. Lipidated LC3B mediates LAP‐dependent
Yi Zhang   +17 more
wiley   +1 more source

Fibrates Inhibit PLTP‐induced M2 Macrophage Infiltration and Increase the Sensitivity of Hepatocellular Carcinoma to ICIs

open access: yesAdvanced Science, EarlyView.
Phospholipid transfer protein(PLTP) plays a critical role in forming a complex with kinase A (AURKA) and P65. This interaction facilitates phosphorylation of P65 at Ser536, leading to the activation of the NF‐κB signaling pathway. Ultimately, this leads to the upregulation of downstream cytokines, including IL‐6, IL‐8, and CSF‐1, which promotes M2 ...
Xinyue Liang   +14 more
wiley   +1 more source

TRMT6‐Mediated m1A Modification of CDK9 mRNA Is a Dual‐Pronged Pathogenic Driver for HBV‐Related Hepatocellular Carcinoma

open access: yesAdvanced Science, EarlyView.
TRMT6‐mediated m1A modification in CDK9 mRNA enhances its mRNA stability and translation efficiency, thereby increasing the protein levels of CDK9. Upregulated CDK9 promotes the progression of HCC by elevating the levels of oncogenic factors including p‐STAT3, MCL1, and BCL‐2. On the other hand, CDK9 phosphorylates TARDBP at Ser254 to activate HBV core
Rui Zhang   +12 more
wiley   +1 more source

Unraveling the Molecular Mechanisms Underlying Spontaneous Multipolar Mitosis Through CIN‐seq

open access: yesAdvanced Science, EarlyView.
Multipolar mitosis, a hallmark of chromosomal instability (CIN), drives tumor heterogeneity but is challenging to study in live cells. Using CIN‐seq, a single‐cell multiomics method, we profiled rare CIN events and identified mechanisms associated with viable multipolar mitosis, including PTEN attenuation, Rho GTPase‐driven cytokinesis failure, and ...
Pin‐Rui Su   +10 more
wiley   +1 more source

A Central Somatic Transmission Mediates Proprioceptive Facilitation of Muscle Pain

open access: yesAdvanced Science, EarlyView.
Zhang et al. uncover a novel central mechanism for persistent muscle pain, in which TRPA1 sensitization in MeV proprioceptive neurons enhances somatic secretion. This, in turn, disinhibits descending pain control from neighboring noradrenergic locus coeruleus neurons via local GABAergic circuits, thereby promoting inflammatory muscle pain.
Xiaoyu Zhang   +15 more
wiley   +1 more source

Paternal Circadian Disruption Impairs Offspring Cognition via Sperm microRNAs

open access: yesAdvanced Science, EarlyView.
Paternal circadian disruption remodels the sperm small RNA payload, elevating miR‐92a‐3p/miR‐25‐3p levels and perturbing early embryonic gene regulatory programs. Microinjection experiments and single‐embryo transcriptomics reveal sex‐specific developmental vulnerabilities, ultimately impairing offspring hippocampal synaptic plasticity and cognition ...
Kexin Zou   +22 more
wiley   +1 more source

Gut Mycobiota‐Associated Tryptophan Catabolites Protect Against Metabolic Dysfunction‐Associated Steatotic Liver Disease

open access: yesAdvanced Science, EarlyView.
ABSTRACT Accumulating evidence suggests that the intestinal microbiota participates in the progression of metabolic dysfunction‐associated steatotic liver disease (MASLD) through microbiota‐host interaction. However, the beneficial role of commensal mycobiota in MASLD progression remains poorly understood.
Shuping Qiao   +11 more
wiley   +1 more source

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