Results 181 to 190 of about 293,211 (259)

Degrading GPX4 via Biomimetic Nanoparticle‐Mediated In Situ Synthesis of Deep‐Learning‐Designed Binder‐Degron Chimeras for Prostate Cancer Therapy

open access: yesAdvanced Science, EarlyView.
A deep‐learning‐designed binder is fused to a combinatorial degron to create a binder‐degron chimera (bdC) that recruits the CUL2‐RING ubiquitin ligase complex. Encapsulation in a prostate‐cancer‐targeted, CD47‐camouflaged nanocarrier enables tumor‐specific in situ bdC expression, triggering GPX4 degradation and ferroptosis, thereby establishing a ...
Si‐Han Zhang   +8 more
wiley   +1 more source

Lactylation‐Mediated HER2 Stabilization Promotes Trastuzumab Resistance in Gastric Cancer

open access: yesAdvanced Science, EarlyView.
Warburg effect‐derived lactate drives HER2 lactylation and trastuzumab resistance. Mechanistically, AARS1‐mediated lactylation stabilizes HER2 by inhibiting USP11‐dependent degradation and concurrently promotes HER2‐EGFR interaction. Importantly, inhibiting HER2 lactylation resensitizes gastric cancer cells to trastuzumab.
Meng Qian   +11 more
wiley   +1 more source

Engineered Peptide Self‐Assembled Nanofibers for Enhanced STING Activation: A Promising Nanodelivery Platform for Immunotherapy of Pediatric Solid Tumors

open access: yesAdvanced Science, EarlyView.
An engineered peptide self‐assembled nanofiber platform, designed to replicate STING–cGAMP binding motifs, facilitates pH‐responsive cytosolic delivery of cGAMP, enhances the endoplasmic reticulum with high efficiency, and robustly activates the STING pathway.
Yubin He   +6 more
wiley   +1 more source

AI‐Designed TREM1‐Targeted LYTAC Nanoparticles Reprogram the Neuroimmune Microenvironment in Traumatic Brain Injury

open access: yesAdvanced Science, EarlyView.
AI‐enabled de novo design of a TREM1 binder, integrated into a BBB‐crossing and macrophage‐targeted nanoplatform, enables TREM1 degradation and attenuates neuroinflammation, thereby promoting neuroprotection and tissue repair after traumatic brain injury. ABSTRACT Secondary neuroinflammation drives progressive damage after traumatic brain injury (TBI),
Yimin Huang   +19 more
wiley   +1 more source

An ATP7A‐Mediated Endogenous Regulation Bio‐Clay Enzyme Enables Self‐Amplified Copper Accumulation for Immunogenic Pyrop

open access: yesAdvanced Science, EarlyView.
A self‐amplifying bio‐clay nanozyme (Bio‐Clayzyme) disrupts tumor metabolic homeostasis through endogenous copper transporter ATPase (ATP7A) downregulation, enhancing cascade catalysis and triggering immunogenic pyroptosis for effective tumor immunotherapy.
Weimin Xie   +4 more
wiley   +1 more source

CXCL3 Antagonism Reverses Systemic Antitumor Immune Memory Impairment Associated With High Tumor Burden and Sensitizes Anti‐PD‐1 Therapy

open access: yesAdvanced Science, EarlyView.
This study reveals that large tumors secrete more chemokine CXCL3, which recruits immunosuppressive neutrophils to the periphery, thereby impairing the activation and memory of systemic tumor‑reactive CD8+ T cells. CXCL3 antagonism restores systemic immune memory and enhances the antitumor efficacy of anti‑PD‑1 therapy, offering a potential strategy to
Ji Wang   +15 more
wiley   +1 more source

Single‐Cell Transcriptomic Profiling Identifies B Cell‐Intrinsic Dysregulation of Sphingolipid Biosynthesis and Could Be Improved by Inhibiting UGCG in Primary Immune Thrombocytopenia

open access: yesAdvanced Science, EarlyView.
This study generates the single‐cell atlas of pathogenic B‐cell subset Bc‐5 in ITP. It identifies RUNX3 as a key survival regulator and uncovers sphingolipid‐driven metabolic reprogramming, validating UGCG inhibition as a therapeutic candidate and building a valuable resource for ITP mechanistic and therapeutic exploration.
Dongmei Luo   +10 more
wiley   +1 more source

Ilexoside K Ameliorates Atherosclerosis by Suppressing CD72hi Macrophages and Blocking CXCL12–CXCR4 Axis to Inhibit Endothelial Pyroptosis

open access: yesAdvanced Science, EarlyView.
CD72hi macrophages drive endothelial pyroptosis and accelerate atherosclerosis through CXCL12–CXCR4‐mediated immune–vascular crosstalk. Ilexoside K suppresses this pathogenic communication by modulating CXCR4‐dependent endothelial responses, reducing inflammation and plaque progression. These findings reveal a macrophage–endothelial regulatory axis and
Xingling He   +11 more
wiley   +1 more source

SCTR–Expressing Astrocyte–Serotonergic Neuron Signaling Drives Sexual Dimorphism in Depression Through KAT7/H4ac–Foxc2 Epigenetic Axis in an AMPK‐Dependent Manner

open access: yesAdvanced Science, EarlyView.
Astrocytic SCTR modulates depressive‐related phenotypes via AMPKα1, whereas lowered Mt1 blunts Megalin‐dependent AMPKα2 signaling in serotonergic neurons. Diminished AMPKα2 hinders KAT7 nuclear translocation, curtails KAT7 occupancy and H4K8ac at the Foxc2 promoter, and represses Foxc2 transcription, revealing cell‐type‐specific AMPK‐linked epigenetic ...
Fantao Meng   +15 more
wiley   +1 more source

Neonatal Sevoflurane Exposure Induces Long‐Term Cognitive Impairment via Epigenetically Mediated MMP9 Activation and Perineuronal Net Disruption in the Hippocampal CA2

open access: yesAdvanced Science, EarlyView.
Hippocampal CA2 perineuronal nets ensheathing excitatory pyramidal neurons are selectively vulnerable to repeated neonatal sevoflurane exposure. Epigenetic upregulation of MMP9 via reduced H3K27me3 disrupts PNN integrity, impairs BDNF–TrkB signaling, and causes synaptic protein loss and dendritic spine deficits, leading to persistent social and spatial
Lirong Liang   +11 more
wiley   +1 more source

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