Results 121 to 130 of about 3,586 (258)

Interpretable Machine Learning Framework for Nb─Si Based Alloy Design with Enhanced Fracture Toughness

open access: yesAdvanced Science, EarlyView.
An interpretable machine learning framework integrating SHAP and PDP analysis identifies critical design descriptors from 139 physicochemical features for Nb─Si alloys. The framework achieves <7% prediction error and guides the discovery of Nb38.5Ti38.5Si3Zr18V2 alloy with 22.791 MPa·m1/2 fracture toughness, breaking the 20 MPa·m1/2 barrier.
Dezhi Chen   +7 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

mTORC2 Phosphorylation of GSDME‐N Drives Cullin4B‐Mediated Proteasomal Degradation to Suppress Pyroptosis and Confer Radioresistance in Small Cell Lung Cancer

open access: yesAdvanced Science, EarlyView.
Radioresistance severely limits the efficacy of therapies for small cell lung cancer (SCLC). This study reveals a novel mechanism of resistance driven by the active suppression of pyroptosis. Specifically, the mTORC2 complex directly phosphorylates GSDME‐N and promotes its CUL4B‐mediated ubiquitination and proteasomal degradation.
Qing‐qing Xu   +11 more
wiley   +1 more source

Targeting KDM3B Elicits Anti‐tumor Immunity by Alleviating SHP1–mediated STING Suppression in Triple–Negative Breast Cancer

open access: yesAdvanced Science, EarlyView.
P3FI–90 treatment targets KDM3B, reshapes the epigenetic landscape, and suppresses SHP1 expression, thereby activating STING–TBK1–IRF3–type I IFN signaling pathway. Consequently, CD8+ T cells are recruited to the tumor site and activated to produce IFN–γ and GZMB, leading to the killing of TNBC cells.
Xiaolong Wang   +8 more
wiley   +1 more source

Protein Structuromics Reveals a Loop‐Controlled Half‐Open Active Pocket Conformation Throughout Fe(II)/α‐ketoglutarate‐Dependent Dioxygenase Catalytic Cycle

open access: yesAdvanced Science, EarlyView.
This study reveals a conserved half‐open active pocket in Fe(II)/α‐ketoglutarate‐dependent dioxygenases through protein structuromics, distinguished by structural features comprising highly flexible loop elements. Enhanced sampling simulations‐guided mutagenesis experiments elucidated how this flexible loop regulates pocket open/closed conformations ...
Lunjie Wu   +10 more
wiley   +1 more source

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