Results 151 to 160 of about 104,409 (252)

Melatonin Alleviates Graft Biliary Fibrosis by Inhibiting VIM+ Cholangiocyte Subcluster via Hypoxia/TGF‐β‐CREM‐VIM Axis

open access: yesAdvanced Science, EarlyView.
Single‐cell RNA sequencing verified the presence of the VIM+ biliary epithelial cell (BEC) in the bile ducts of NAS patients. The hypoxia/TGF‐β‐CREM‐VIM axis mediated phenotypic switch toward VIM+ BEC is validated using a hypoxia/TGF‐β‐stimulated cellular model, a rat liver transplantation model, BEC‐specific Crem conditional knockout rats, and BEC ...
Zhaoyi Wu   +14 more
wiley   +1 more source

PDIA6–SCD1 Axis Rewires Lipid Metabolism to Drive Gastric Cancer Progression

open access: yesAdvanced Science, EarlyView.
Protein disulfide isomerase A6 (PDIA6) is identified as an oncogenic driver in gastric cancer. PDIA6 directly binds and stabilizes SCD1 by limiting its ubiquitin–proteasome‐mediated degradation, thereby sustaining monounsaturated fatty acid (MUFA)‐enriched lipid homeostasis and lipid metabolic reprogramming.
Zhen Tian   +13 more
wiley   +1 more source

Cholesterol‐Mediated Metabolic‐mechanotransductive Crosstalk Orchestrates Castration Resistance in Prostate Cancer

open access: yesAdvanced Science, EarlyView.
Full androgen deprivation (FAD) induces paracrine cholesterol in prostate cancer that drives the polarization of cancer‐associated fibroblasts (CAFs) and subsequent elevated matrix stiffness. Matrix stiffness in turn potentiates tumor cell survival under FAD pressure via dual mechanotransductive activation of the IRE1α‐XBP1s stress‐response axis ...
Shaojie Liu   +20 more
wiley   +1 more source

Targeting Lactate‐Driven Stromal Autophagy via MCT1 Disrupts the Immunosuppressive Niche and Sensitizes Pancreatic Cancer to PD‐1 Blockade

open access: yesAdvanced Science, EarlyView.
Tumor‐derived lactate activates PSCs through MCT1‐mediated Vps34 lactylation and autophagy. These activated PSCs secrete CXCL9/10, upregulating PD‐1 on CD8+ T cells via the CXCR3/STAT3 axis to foster immunosuppression. Disrupting this metabolic crosstalk by targeting MCT1 effectively sensitizes pancreatic cancer to PD‐1 blockade, presenting a promising
Wenfeng Zhuo   +14 more
wiley   +1 more source

A Conserved DT2‐bZIP66‐NF‐YC4 Regulatory Module Confers Drought Tolerance in Rice and Arabidopsis

open access: yesAdvanced Science, EarlyView.
This study identifies a conserved tripartiteDT2–bZIP66–NF‐YC4 transcriptional module that enhances rice drought tolerance by activating stress‐responsive genes. This regulatory complex is functionally conserved across cereals and Arabidopsis, providing promising targets for engineering drought‐resilient crops. ABSTRACT Drought stress severely restricts
Jun Shen   +18 more
wiley   +1 more source

Mechanical Activation of Piezo1 Drives Osteoarthritis Through Kdm5c‐Mediated Epigenetic Silencing

open access: yesAdvanced Science, EarlyView.
Excessive mechanical stress activates Piezo1, triggering Ca2+‐dependent cytoskeletal forces that deform the nucleus and reduce H3K4me3. Kdm5c demethylates H3K4me3 at Col2a1 and Runx3 promoters. Kdm5c knockout rescues degradation. Repurposed telmisartan directly inhibits Kdm5c, blocking this axis and showing disease‐modifying efficacy in mouse OA models
Tianyou Kan   +13 more
wiley   +1 more source

NAD+ Metabolism Licenses Zygotic Genome Activation via PARP7‐Mediated ADP‐Ribosylation of UHRF1 in Mouse Early Embryos

open access: yesAdvanced Science, EarlyView.
This study uncovers a metabolic‐epigenetic axis licensing zygotic genome activation (ZGA) in mouse embryos. A developmental decline in NAD+ levels activates PARP7, which mono‐ADP‐ribosylates and stabilizes UHRF1. This modification promotes the establishment of permissive histone acetylation marks, thereby facilitating timely ZGA.
Guangyi Cao   +13 more
wiley   +1 more source

Radiation‐Induced Tumor‐Intrinsic LTβR N‐Glycosylation Suppresses Pyroptosis Through TRIM28‐Mediated PCBP2 SUMOylation to Promote Gastric Cancer Radioresistance

open access: yesAdvanced Science, EarlyView.
Radiotherapy triggers LTβR N‐glycosylation, enhancing its overall protein stability and nuclear retention. This accumulation drives TRIM28‐mediated PCBP2 SUMOylation, suppressing pyroptosis and conferring gastric cancer radioresistance. Therapeutically, a targeted nanoplatform (cRGD‐Lipo@EMD) effectively disrupts this regulatory axis, offering a highly
Weijie Zang   +8 more
wiley   +1 more source

UBE2O Drives Immune Evasion and Radioimmunotherapy Resistance in Lung Cancer by Degrading CDKL1 to Induce PD‐L1 Transcription

open access: yesAdvanced Science, EarlyView.
UBE2O targets CDKL1 for the degradation to upregulate PD‐L1 expression and promotes resistance to radioimmunotherapy in lung cancer, supporting the potential of targeting UBE2O as a promising therapeutic strategy. ABSTRACT Resistance to radioimmunotherapy is one of the primary causes of treatment failure in lung cancer patients; however, the underlying
Huichan Xue   +6 more
wiley   +1 more source

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