Results 201 to 210 of about 265,912 (308)

A Plug‐and‐Play Platform for Customizing Multivalent Degraders and Degrader‐Drug Conjugates

open access: yesAdvanced Science, EarlyView.
Membrane proteins remain challenging targets for conventional TPD approaches. Here, the authors develop UPTAB, a modular platform leveraging ultrahigh‐affinity orthogonal Im/CL protein pairs for lysosomal degradation of membrane proteins. Mono‐targeted (Type‐I), dual‐targeted (Type‐II), and tri‐targeted (Type‐III) UPTABs enable simultaneous degradation
Mengqing Zhao   +7 more
wiley   +1 more source

Lactoferrin Deficiency During Lactation Causes Adult Obesity‐Related Metabolic Disease Through Persistent Adipose Dysfunction Driven by Impaired Adipocyte Development

open access: yesAdvanced Science, EarlyView.
Lactational lactoferrin deficiency exerts lasting effects on epididymal adipose tissue development from lactation into adulthood: it impairs adipocyte hyperplasia and induces pathological hypertrophy, resulting in lower body weight yet exacerbated metabolic dysfunction under a high‐fat diet in adulthood.
Qin An   +11 more
wiley   +1 more source

Ciclopirox Olamine Inhibits the NLRP3 Inflammasome to Alleviate Inflammatory Diseases

open access: yesAdvanced Science, EarlyView.
There is no drug targeting the NLRP3 inflammasome that has been approved for use in clinical settings. Ciclopirox olamine (CPX), an antifungal agent approved by the US Food and Drug Administration (FDA), is identified as a specific and potent NLRP3 inflammasome inhibitor. CPX targets the NACHT domain of NLRP3 at Y381 to impair NLRP3 oligomerization and
Xinyu Xia   +7 more
wiley   +1 more source

Aptamer‐Targeted PrPC Drives Colorectal Cancer Metastasis via a LYN‐STAT3 Complex and Enables Liquid Biopsy Detection

open access: yesAdvanced Science, EarlyView.
The aptamer WHY‐3E identifies PrPC as a CRC driver. Stabilized by USP18, endocytosed PrPC forms a LYN/STAT3 complex, upregulating MSN transcription to promote metastasis. Crucially, WHY‐3E sensitively detects PrPC‐positive circulating exosomes, establishing a robust theoretical foundation for non‐invasive clinical diagnostics.
Chunlin Wang   +23 more
wiley   +1 more source

A Non‐Canonical Core Transcriptional Regulatory Circuit Orchestrates Chromatin Reprogramming to Drive Osimertinib Resistance in Non‐Small Cell Lung Cancer

open access: yesAdvanced Science, EarlyView.
A non‐canonical core transcriptional regulatory circuit, composed of ID3, SMAD3, and NR2F2, drives Osimertinib resistance in non‐small cell lung cancer through super‐enhancer‐mediated activation of EPAS1, which couples neuroendocrine differentiation with ferroptosis evasion.
Aochu Liu   +15 more
wiley   +1 more source

PGK1 Suppresses CD8+ T Cell‐Mediated Antitumor Immunity Through CCL2/CCR2/Tumor‐Associated Macrophages Axis in Hepatocellular Carcinoma

open access: yesAdvanced Science, EarlyView.
PGK1 in tumor cells upregulates CCL2 expression through activation of the AKT/GSK‐3β/β‐catenin signaling axis, thereby promoting the recruitment and M2 polarization of TAMs and ultimately impairing the infiltration and activation of CD8+ T cells within the HCC tumor microenvironment. ABSTRACT Patients with advanced hepatocellular carcinoma (HCC) have a
Xi Liu   +17 more
wiley   +1 more source

Non-receptor tyrosine kinase signaling pathways and therapeutic implications. [PDF]

open access: yesSignal Transduct Target Ther
Hossain MDA   +4 more
europepmc   +1 more source

SuFEx‐Enabled Reprogramming of Flavonoids for Selective α‐Glucosidase Covalent Inhibition

open access: yesAdvanced Science, EarlyView.
Selective inhibition of intestinal α‐glucosidase remains limited by poor enzyme specificity and off‐target metabolic effects. Here, SuFEx click chemistry is used to reprogram natural flavonoids into covalent inhibitors with enhanced α‐glucosidase selectivity and controlled reactivity. This strategy enables effective regulation of carbohydrate digestion
Fengyu Guo   +14 more
wiley   +1 more source

The multifaceted roles of receptor tyrosine pseudokinases in cellular signalling. [PDF]

open access: yesBiochem Soc Trans
Park EC   +4 more
europepmc   +1 more source

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