Results 141 to 150 of about 318,069 (262)

Potent and Selective IGF‐IIR‐Recruiting Bifunctional Molecules for Targeted Lysosomal Degradation of Extracellular and Membrane Proteins

open access: yesAdvanced Science, EarlyView.
Lysosome‐targeting chimeras (LYTACs) enable degradation of extracellular and membrane proteins via lysosomal trafficking. We report a novel IGF‐II mutant (Del1–7, Y27L) that selectively engages IGF‐IIR while avoiding IGF‐IR and IR‐A. mutIGF‐II–based LYTACs enhance target internalization and degradation and support a genetically encodable, all‐protein ...
Yuan Zhao   +16 more
wiley   +1 more source

Circular RNA circNrip1 Interacts with SYNCRIP to Promote Neuropathic Pain by Stabilizing Tlr2 mRNA in Primary Sensory Neurons

open access: yesAdvanced Science, EarlyView.
Model of circNrip1 (cNrip1) upregulation driving neuropathic pain mechanisms. After peripheral nerve injury, increased FUS triggers the formation and upregulation of cNrip1 in injured DRG neurons. Upregulated cNrip1 recruits SYNCRIP to the 3′‐UTR of Tlr2 mRNA by binding to both, thereby promoting SYNCRIP‐triggered Tlr2 mRNA stability and increasing ...
Xiaozhou Feng   +14 more
wiley   +1 more source

SMAD4 Palmitoylation Drives a Metabolic‐Transcriptional Circuit to Promote Tumorigenesis and Confers Radiosensitivity in Pancreatic Cancer

open access: yesAdvanced Science, EarlyView.
This study identifies palmitoylation as a novel regulatory modification of SMAD4, mediated by ZDHHC22/APT2. It activates fatty acid synthesis, creating a self‐reinforcing SMAD4–FASN–palmitate feedback loop that drives pancreatic cancer growth and enhances radiotherapy sensitivity.
Yang Wang   +16 more
wiley   +1 more source

NUP85 Mediates Endoplasmic Reticulum Stress through the USP47/ASK1 Signaling Pathway to Regulate the Progression of Liver Fibrosis

open access: yesAdvanced Science, EarlyView.
In the present study, we have demonstrated that the NUP85‐USP47‐ASK1 signaling pathway may have regulated the progression of liver fibrosis through modulating ERS. Additionally, we have developed a CREKA‐coupled liposome to target delivery of MV, a pharmacological inhibitor of NUP85, to activated HSCs, thereby attenuating liver fibrosis. ABSTRACT Liver
Dashuai Yang   +11 more
wiley   +1 more source

A Microbial Lipid‐ATP Synthase Axis Fuels NK Cell Antitumor Activity

open access: yesAdvanced Science, EarlyView.
This study focuses on the mechanism by which gut microbiota‐derived outer membrane vesicles (OMVs) regulate NK cell antitumor activity. B. intestinalis is identified to decrease extra‐intestinal tumor growth via its OMVs enriched in sphingosine (SP).
Kaiyuan Yu   +16 more
wiley   +1 more source

PSMA8‐Containing 20S Proteasome Regulates Spermiogenesis and Male Fertility

open access: yesAdvanced Science, EarlyView.
PSMA8 assembles s20S proteasome that degrades specific substrates in elongating spermatids. Degradation of s20S‐substrates activates translation of FXR1‐target mRNAs, which are essential for mitochondrial sheath formation and sperm morphogenesis.
Huiwen Cao   +7 more
wiley   +1 more source

RENAL‐CHIP: Rejection Evaluation via Non‐Invasive Analysis of Circulating Podocytes With Herringbone‐Chip Isolation Platform

open access: yesAdvanced Science, EarlyView.
RENAL‐CHIP converts 1 mL of peripheral blood into a biopsy‐equivalent readout of renal‐allograft fate. By magnetic capture and release of donor‐derived circulating podocytes through a herringbone microfluidic chip, 84% capture, 96% release and single‐cell RNA evidence of rejection‐specific immunity are achieved.
Juan Song   +11 more
wiley   +1 more source

Endogenous Ceramide 24:1 Constrains Th17‐Driven Neutrophilic Inflammation by Antagonizing EP2 Signaling

open access: yesAdvanced Science, EarlyView.
Cer24:1 levels are reduced in neutrophilic asthma and inversely correlate with disease severity and airway neutrophilia. Restoring Cer24:1 suppresses pathogenic Th17 differentiation by engaging EP2 on CD4+ T cells, thereby dampening the JAK2–STAT3–RORγt axis and reducing IL‐17 production.
Huan Liu   +11 more
wiley   +1 more source

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