Results 231 to 240 of about 1,288,650 (300)

Uhrf1‐Mediated PKM2 Degradation via Ubiquitination Alleviates Inflammation and Pyroptosis in Inflammatory Bowel Disease

open access: yesAdvanced Science, EarlyView.
Uhrf1‐mediated PKM2 ubiquitination and degradation repressed the nuclear translocation of PKM2, and EPT served as a molecular glue capable of targeting the Uhrf1–PKM2 complex to alleviate the IBD course, suggesting that the Uhrf1–PKM2 axis was a previously unrecognized strategy for treating IBD.
Juan Zhang   +9 more
wiley   +1 more source

Macrophage RSAD2 Couples mtDNA Synthesis With a Self‐Amplifying Inflammatory Circuit to Orchestrate Tissue Repair

open access: yesAdvanced Science, EarlyView.
Macrophage RSAD2 dually regulates CMPK2—the rate‐limiting enzyme for mitochondrial DNA synthesis—by suppressing its ubiquitination and promoting its phosphorylation via Csnk2a2 recruitment. This amplifies mtDNA production, which simultaneously activates a cGAS‐STING‐IRF3‐RSAD2 feedforward loop and the NLRP3 inflammasome, driving a self‐sustaining ...
Haomiao Yuan   +16 more
wiley   +1 more source

The Cancer Cell Metabolic Reprogramming Remodels the Tumor Microenvironment: Molecular Mechanisms and Therapeutic Strategies

open access: yesAdvanced Science, EarlyView.
This review elucidates how cancer cell metabolic reprogramming—across glucose, lipid, amino acid, and nucleotide pathways—remodels the tumor microenvironment to suppress anti‐tumor immunity and promote immune escape. Targeting these metabolic axes offers promising strategies to overcome immunotherapy resistance and enhance cancer treatment.
Guoqing Xiang   +5 more
wiley   +1 more source

OAF Blocks SIAH1‐Mediated Degradation of SCPX, a Therapeutic Strategy for MASLD

open access: yesAdvanced Science, EarlyView.
This study shows OAF directly binds to SCPX and inhibits its interaction with the E3 ligase SIAH1, thereby protecting SCPX from ubiquitin‐dependent degradation and stabilizing its levels. This OAF‐SCPX axis represents a novel pathway in lipid homeostasis, highlighting OAF as a promising therapeutic candidate for MASLD.
Zongxi Li   +11 more
wiley   +1 more source

Tau Aggregate Imaging and Transcriptomics of Alzheimer's Disease Brain at Different Stages of Disease

open access: yesAdvanced Science, EarlyView.
The protein aggregates and gene expression in the middle temporal gyrus (MTG) and somatosensory cortex (SOM) of the postmortem brains of 13 Alzheimer's disease patients were studied in detail, revealing that small hyperphosphorylated tau aggregates increase with Braak stage driven by microglial inflammation.
Elizabeth A. English   +9 more
wiley   +1 more source

Natural Product Toosendanin Suppresses the Malignant Development of Skin Melanoma by Targeting BNC2 for Degradation

open access: yesAdvanced Science, EarlyView.
BNC2 exhibits context‐dependent opposing functions across multiple cancer types. This study reveals BNC2 as an oncogenic driver of melanoma proliferation and metastasis through transcriptional activation of PIK3CA. The natural compound TSN simultaneously degrades BNC2 and its oncogenic partner SMAD3 via CRBN‐dependent ubiquitination.
Hui Dai   +7 more
wiley   +1 more source

Grtp1 Safeguards Against Paternal Reproductive Aging and Intergenerational Behavioral Deficits by Preserving Redox Homeostasis

open access: yesAdvanced Science, EarlyView.
This study identifies that Grtp1 maintains germline redox homeostasis by interacting with PRDX1/4‐TXN to antagonize paternal reproductive aging. Growth hormone restores Grtp1 expression, rectifies aberrant sperm DNA methylation, and ameliorates intergenerational anxiety and social deficits, highlighting the GH‐GRTP1 axis as a promising intervention ...
Yingdong Liu   +23 more
wiley   +1 more source

Carbohydrate‐Mediated Cellular Uptake of Boronic Acid Hybrids In Cellulo and Insulin‐Deficient Zebrafish: Live Imaging and Application of Multiphoton FLIM

open access: yesAdvanced Science, EarlyView.
Boronic acid‐based fluorescent hybrids have been used as part of a versatile platform for real‐time metabolic bioimaging across cellular and organismal scales. Including glucose‐responsive imaging in living cells and in an insulin‐deficient vertebrate model, this work opens new opportunities for the development of precision diagnostics, metabolic ...
Haobo Ge   +13 more
wiley   +1 more source

Discovery and Optimization of AMT‐676, a CDH17‐Targeting ADC for the Treatment of Advanced Gastrointestinal Cancers

open access: yesAdvanced Science, EarlyView.
AMT‐676 is a novel antibody‐drug conjugate targeting CDH17, an adhesion molecule uniquely exposed on gastrointestinal tumor surfaces. Engineered with an optimized exatecan payload, it demonstrates profound tumor regression and a robust bystander effect across diverse preclinical models.
Ying‐nan Wang   +21 more
wiley   +1 more source

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