Results 131 to 140 of about 1,399 (214)

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

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

The Multidisciplinary Ice Core

open access: yesThe Multidisciplinary Ice Core
Ice-core physics and climate research undoubtedly form a very successful partnership. Nevertheless, even the best union may sometimes suffer under the wearing of time. Multidisciplinarity may support the stability of this partnership, by helping ice-core physics to become more independent and dynamic, as well as a better partner to other disciplines ...
openaire  

NIBV Induces Incomplete Autophagy via AMPK‐TFEB, Causing Kidney Injury in Chicks

open access: yesAdvanced Science, EarlyView.
This study reveals that NIBV can inhibit the nuclear translocation of TFEB by suppressing the expression of AMPK, leading to the blockade of autophagolysosomal functions, in turn increasing NIBV replication and triggering severe kidney injury in chicks.
Cheng Huang   +10 more
wiley   +1 more source

Functional Analysis of Ligand‐Gated Chloride Channels in a Cnidarian Sheds Light on the Evolution of Inhibitory Signaling

open access: yesAdvanced Science, EarlyView.
We uncover a large variety of putative inhibitory ligand‐gated ion channels (LGICs) in the phylum Cnidaria, the sister group to all bilaterian animals. Phylogenetic analysis suggests a complex evolutionary history of inhibitory LGICs with diverse neurotransmitter ligands.
Abhilasha Ojha   +13 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

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