Results 31 to 40 of about 1,029 (179)

PRMT5‐Dependent Stabilization of VPS34 Orchestrates Copper Trafficking to Shield Cancer Cells from Cuproptosis and Radiotherapy

open access: yesAdvanced Science, EarlyView.
Radioresistance arises partly from tumor cells evading cuproptosis via unknown defenses. This study reveals that the PRMT5‐VPS34 axis acts as a radiation‐activated anticuproptotic mechanism: PRMT5 methylates VPS34 at Arg174, recruiting USP10 to remove K48‐linked ubiquitination and prevent degradation.
Wei Chen   +17 more
wiley   +1 more source

Targeting the ATX‐LPA Axis Overcomes TKI Resistance and Immunosuppression in Renal Cell Carcinoma via Dual Inhibition of AKT/mTOR and TBK1/IRF3 Pathways

open access: yesAdvanced Science, EarlyView.
ABSTRACT Background Therapeutic resistance limits durable survival in advanced/metastatic renal cell carcinoma (RCC) treated with first‐line tyrosine kinase inhibitor (TKI) plus immune checkpoint inhibitor (ICI). We sought to define key resistance drivers and actionable targets.
Jinchen Luo   +16 more
wiley   +1 more source

Multi‐tissue Metabolic GWAS and Drought‐Responsive Multi‐omics Reveal the Genetic Basis of the Quinoa Metabolome

open access: yesAdvanced Science, EarlyView.
A multi‐omics framework combining multitissue genome‐wide association studies, metabolomics, transcriptomics, proteomics, and functional validation uncovers the genetic basis of specialized metabolism in quinoa. The study identifies hundreds of metabolite‐associated loci, prioritizes candidate genes for saponin, betalain, and flavonoid biosynthesis ...
Julia von Steimker   +11 more
wiley   +1 more source

Introducing Borsantrazole: A Trifunctional Boron‐Based Pyrazole That Extends the Lifespan of Amyotrophic Lateral Sclerosis Mice

open access: yesAdvanced Science, EarlyView.
Herein we report a boron‐based pyrazole, (Borsantrazole ‐ a small molecule that selectively targets oxidative stress) that significantly increases survival, reduces weight loss, delays disease onset, and affects global protein changes in the SOD1‐G37R mouse model of ALS.
Nitesh Sanghai   +9 more
wiley   +1 more source

HMGCR‐Driven Cholesterol Metabolism Promotes Osteoarthritis Progression by Accelerating Synovial Fibroblast Senescence

open access: yesAdvanced Science, EarlyView.
In the pathological context of osteoarthritis (OA), the phosphorylation of AKT1 at Ser473 enhances its binding to Lys140 of Insig1, which facilitates the formation of AKT1–Insig1 complex. Subsequently, the activation of AKT1 promotes the phosphorylation of Insig1 at Ser189, potentially enhancing the dissociation of Insig1 from sterol regulatory element‑
Xiaoqi Zhang   +19 more
wiley   +1 more source

Single‐cell Transcriptome Profiling Reveals Gene Regulatory Networks and Key Genes in the Root Epidermis and Cortical Cells Associated with Early Nodulation in Glycine Max

open access: yesAdvanced Science, EarlyView.
Single‐cell transcriptomics of soybean roots soon after rhizobial inoculation reveals epidermal and cortical cell‐specific programs and gene‐regulatory networks acting in symbiosis establishment. We identify an ethylene‐driven regulatory circuit involving WRKY6.3/6.4 transcription factors targeting select Nod19 genes that promotes infection‐thread ...
Yongbin Zhuang   +17 more
wiley   +1 more source

Large‐scale Whole‐Exome Sequencing Defines the Protein‐Coding Architecture of Retinal Structure, Visual Function, and Major Blinding Diseases

open access: yesAdvanced Science, EarlyView.
Large‐scale whole‐exome sequencing in 356,982 UK Biobank participants defines the protein‐coding architecture of retinal structure, visual function, and major blinding diseases. Pleiotropic genes, including CFI, C3, and RIOX1, bridge multiple retinal phenotypes, while experimental validation of FYB2 implicates RPE barrier dysfunction, providing ...
Jianqing Li   +23 more
wiley   +1 more source

Ubiquitination of ACSL4 by Parkin Suppresses Ferroptosis and Rescues Glucocorticoid‐Induced Bone Loss

open access: yesAdvanced Science, EarlyView.
GCs reduce Parkin, leading to ACSL4 accumulation and PUFA‐phospholipid‐driven ferroptosis in BMSCs, which impairs osteogenesis and promotes adipogenesis, causing GIOP. Parkin restoration (via OE‐Parkin or Parkin‐LNP@DSS6) ubiquitinates and degrades ACSL4, inhibiting ferroptosis, rescuing bone formation, and rescues GIOP bone loss.
Li‐jiang Han   +16 more
wiley   +1 more source

PEAR1 Promotes Glucose Metabolism Reprogramming in Sepsis‐Associated Acute Lung Injury via AARS1‐Mediated HIF‐1α Lactylation

open access: yesAdvanced Science, EarlyView.
This study revealed that a PEAR1/HIF‐1α/ glycolysis/lactate/H3K18la positive feedback loop in PMVECs that drives the development of S‐ALI. Mechanistically, PEAR1 mediates the binding of HIF‐1α to AARS1, leading to the lactylation of HIF‐1α, the primary lactylation site of which is K172.
Shuai Li   +15 more
wiley   +1 more source

An Artificially Selected Cytokinin‐Pathway Transcription Factor Balances Soybean Yield and Pathogen Resistance

open access: yesAdvanced Science, EarlyView.
A cytokinin pathway transcription factor, RR2b, was artificially selected during soybean domestication and improvement based on its differential transcriptional activity, which correlates with ATT repeat polymorphisms in its promoter. RR2b balances yield and defense by fine‐tuning its expression level and offers a promising target for decoupling trade ...
Qun Ma   +11 more
wiley   +1 more source

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