Results 91 to 100 of about 146,333 (267)

Astrocytic Phenotypic Switching in Posterior Piriform Cortex Orchestrates Bone Cancer Pain–Depression Comorbidity via Purinergic–Noradrenergic Signaling

open access: yesAdvanced Science, EarlyView.
Bone cancer pain and depression share a common origin: astrocytic A2‐to‐A1 transition in the posterior piriform cortex. This phenotypic shift disrupts the ATP–adenosine–A2AR–norepinephrine axis, simultaneously driving nociceptive and affective dysfunction.
Jiang‐Ping Liu   +14 more
wiley   +1 more source

TOLLIP Inhibits Psoriasis Progression via Suppressing PKM2‐Mediated Glycolysis in Keratinocytes

open access: yesAdvanced Science, EarlyView.
In this study, we identify TOLLIP as a critical regulator of psoriasis pathogenesis through its modulation of glycolytic metabolism. Our findings establish the TOLLIP‐PKM2‐glycolysis axis as a key mechanism linking metabolic reprogramming to psoriasis pathogenesis, and propose TOLLIP as a promising therapeutic target.
Xiuhuan Jiang   +11 more
wiley   +1 more source

Cysteine Redox State Governs the Condensation Pathway of Hendra Virus W Protein and Differentially Impacts Type I IFN and NF‐κB Signaling

open access: yesAdvanced Science, EarlyView.
The cysteine redox state of the Hendra virus W (WHeV) protein controls assembly into fibrils or amorphous aggregates, with residues 2–29 required for fibrillation. In cells, WHeV forms different types of nuclear condensates. Impaired ability to form redox‐sensitive, non‐filamentous condensates reduces WHeV inhibition of the NF‐κB pathway, while it ...
Frank Gondelaud   +12 more
wiley   +1 more source

BIN1 and ALDH1B1 Deficiency in Colonic Smooth Muscle Drives Mitochondrial Dysfunction and Fibrosis in Slow‐Transit Constipation

open access: yesAdvanced Science, EarlyView.
Slow‐transit constipation (STC) is a disabling motility disorder with unclear smooth‐muscle mechanisms. Spatial proteomic analysis of STC patient colon reveals both the central pathogenic role of smooth muscle cells (SMCs) in STC and novel regulators of intestinal motility, BIN1 and ALDH1B1.
Jianbo Liu   +10 more
wiley   +1 more source

Astrocytic LMP2 Coordinates NF‐κB and TGF‐β1/Smad3 Signaling to Drive Neuroinflammation after Cerebral Ischemia/Reperfusion

open access: yesAdvanced Science, EarlyView.
ABSTRACT Astrocyte reactivity critically shapes neuroinflammatory outcomes after ischemic stroke, yet the upstream regulators governing astrocyte state transitions remain incompletely defined. Here, we identify the immunoproteasome subunit low molecular weight protein 2 (LMP2) as an important modulator of astrocyte functional remodeling following ...
Yanguang Mao   +7 more
wiley   +1 more source

Mitochondrial SLC25A46 Rewires Fatty Acid Oxidation to Promote Cell Proliferation and Ferroptosis Evasion in Ovarian Cancer by Stabilizing CACT

open access: yesAdvanced Science, EarlyView.
Mitochondrial SLC25A46 is upregulated in ovarian cancer (OC) and correlates with poor prognosis. SLC25A46 stabilizes CACT to activate fatty acid oxidation, increasing ATP and NADPH production to drive cell proliferation and ferroptosis evasion. SLC25A46 silencing sensitizes OC cells to ferroptosis and carboplatin, offering a promising therapeutic ...
Yunge Gao   +9 more
wiley   +1 more source

Lilrb4a Suppression Reprograms Microglia to Mitigate APOE4‐Associated Amyloid Plaques and Cerebral Amyloid Angiopathy in Association With a PPAR‐Linked Pro‐Clearance State

open access: yesAdvanced Science, EarlyView.
Targeting Lilrb4a in Apolipoprotein E4 (APOE4)‐associated Alzheimer's disease (AD) reprograms microglia toward a beneficial, phagocytic state. Genetic deletion or antisense inhibition of Lilrb4a suppresses p‐SHP2/NF‐κB/STAT1 signaling, restores PPAR‐linked lipid and energy metabolism, and reduces amyloid plaque burden and cerebral amyloid angiopathy ...
Changxu Nie   +12 more
wiley   +1 more source

Dynamic Regulation of Endogenous Transcription Factor Hubs at Single‐Molecule Resolution

open access: yesAdvanced Science, EarlyView.
This study combines single‐molecule microscopy and genome editing to characterize the dynamic behaviors of endogenous oncofusion transcription factor EWS::FLI1 in Ewing sarcoma cells. EWS::FLI1 forms neomorphic hubs that dynamically assemble and dissolve. The hubs are regulated during mitosis, by RNA, and by specific chemicals.
Shawn Yoshida   +4 more
wiley   +1 more source

A Non‐Canonical Role of SMAD4 in Regulating 3D Genome Architecture to Inhibit Lung Squamous Cell Carcinoma Development

open access: yesAdvanced Science, EarlyView.
SMAD4 is identified as a guardian of 3D genome architecture in lung squamous cell carcinoma. Loss of SMAD4 unleashes EP300 at chromatin loop anchors, strengthening enhancer–promoter looping and H3K27ac at the SOX2 locus to drive aberrant SOX2 activation and tumor cell proliferation.
Qian Tang   +33 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

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