Results 241 to 250 of about 431,758 (295)

Bilirubin Targeting WNK1 to Alleviate NLRP3‐Mediated Neuroinflammation

open access: yesAdvanced Science, EarlyView.
At physiological concentrations, bilirubin binds to the kinase domain of WNK1, thereby augmenting its activity and facilitating the phosphorylation of downstream SPAK/OSR1. This phosphorylation inhibits KCC2 activity, leading to elevate intracellular chloride levels in neurons.
Linfei Mao   +14 more
wiley   +1 more source

Elevated Histone Lactylation Mediates Ferroptosis Resistance in Endometriosis Through the METTL3‐Regulated HIF1A/HMOX1 Signaling Pathway

open access: yesAdvanced Science, EarlyView.
This study reveals that histone lactylation, a modification derived from lactate, plays a crucial role in ferroptosis resistance in ectopic endometrial stromal cells. This resistance is mediated via the HIF1A/HMOX1 pathway regulated by METTL3. In vivo, a combination of 2‐DG and erastin shows promise as an effective treatment for endometriosis ...
Zongwen Liang   +8 more
wiley   +1 more source

Topoisomerase I Inhibition in ETV4‐overexpressed Non‐Small Cell Lung Cancer Promotes Replication and Transcription Mediated R‐Loop Accumulation and DNA Damage

open access: yesAdvanced Science, EarlyView.
The oncogenic ETS factor ETV4 exerts a pleiotropic control over DNA replication both in a transcription‐dependent and ‐independent fashion in NSCLC cells. High‐ETV4 expression leads to R‐loop formation and DNA damage in response to TOP1 inhibition.
Jiaxi Zhang   +14 more
wiley   +1 more source

Muscle‐Derived Small Extracellular Vesicles Mediate Exercise‐Induced Cognitive Protection in Chronic Cerebral Hypoperfusion

open access: yesAdvanced Science, EarlyView.
sEVs have a critical role in orchestrating interorgan crosstalk and mediating exercise‐induced therapeutic effects. Lin et al. demonstrates that sEVs miR‐17/20a‐5p mediates the muscle‐brain crosstalk and emphasizes the central role of mTOR signaling in executing molecular programs that can protect brain health in response to exercise. Abstract Physical
Huawei Lin   +21 more
wiley   +1 more source

EGR1 Promotes Craniofacial Bone Regeneration via Activation of ALPL⁺PDGFD⁺ Periosteal Stem Cells

open access: yesAdvanced Science, EarlyView.
ALPL+PDGFD+ (AP+) cells are distinct calvarial periosteal stem cells (PeSCs) with diminished postnatal activity. EGR1 drives PeSCs development via BMP signaling through its Znf2 domain and activates them via CTNNB1/WNT10B signaling through its Znf2/3 domains.
Yang Li   +15 more
wiley   +1 more source

METTL14‐Mediated M6A Modification of LINC01094 Induces Glucose Metabolic Reprogramming in Breast Cancer by Recruiting the PKM2/JMJD5 Complex

open access: yesAdvanced Science, EarlyView.
METTL14/IGF2BP2‐mediated m6A modification drives LINC01094 upregulation in BC. Then, LINC01094 interacts with PKM2 monomers to promote their dimerization, while serving as a flexible scaffold to facilitate the assembly of the PKM2/JMJD5 complex, synergistically stabilizing PKM2 dimers and enhancing their nuclear translocation.
Mengqi Wang   +8 more
wiley   +1 more source

Acod1 Promotes PAD4 Ubiquitination via UBR5 Alkylation to Modulate NETosis and Exert Protective Effects in Sepsis

open access: yesAdvanced Science, EarlyView.
In this study, Acod1 knockout in CLP mice significantly increases peripheral blood NET levels, exacerbating inflammation, organ damage, and reducing survival. Further research shows that UBR5 interacts with PAD4, a key NET formation protein. Acod1/itaconate (ITA) enhances the enzymatic activity of UBR5 by alkylating the Cys2768 site, promoting the K48 ...
Huifan Liu   +10 more
wiley   +1 more source

Cryptic Splicing of GAP43 mRNA is a Novel Hallmark of TDP‐43‐Associated ALS and AD

open access: yesAdvanced Science, EarlyView.
TDP‐43 dysfunction disrupts RNA processing, inducing cryptic exon 4a1 inclusion in GAP43 and reducing its protein levels. This aberrant splicing impairs axonal regeneration and contributes to neurodegeneration in ALS and AD. RNA‐seq of patient brains reveals GAP43 downregulation and 4a1 upregulation, identifying cryptic exon 4a1 as a potential ...
Mingming Yang   +9 more
wiley   +1 more source

USP10 Inhibits Ferroptosis via Deubiquinating POLR2A in Head and Neck Squamous Cell Carcinoma

open access: yesAdvanced Science, EarlyView.
This study identifies USP10 as a novel deubiquitinase that antagonizes ferroptosis in head and neck squamous cell carcinoma (HNSCC). Mechanistically, USP10 directly stabilizes POLR2A protein through post‐translational deubiquitination, enabling POLR2A‐mediated transcriptional activation of SLC7A11, a key ferroptosis inhibitor.
Diekuo Zhang   +13 more
wiley   +1 more source

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