Results 221 to 230 of about 11,506,565 (250)

RNase H As Gene Modifier, Driver of Evolution and Antiviral Defense. [PDF]

open access: yesFront Microbiol, 2017
Moelling K   +3 more
europepmc   +1 more source

Matrix Stiffness Orchestrates Mesenchymal Stem Cell Lineage Commitment Toward Osteogenesis and Adipogenesis Through the PIEZO1/SP1/STC2 Axis

open access: yesAdvanced Science, EarlyView.
Matrix stiffness directs mesenchymal stem cell lineage commitment through PIEZO1‐dependent activation of the SP1/STC2 pathway. Stiff matrices favor osteogenesis and suppress adipogenesis, whereas the loss of PIEZO1 function impairs early bone formation. STC2 retains lineage‐regulatory activity even when PIEZO1 is inactive.
Shuo Zhang   +12 more
wiley   +1 more source

AS‐TLC‐Based High‐Throughput Screening Integrated with CuAAC Optimization Strategy Facilitates the Rapid Discovery of YTHDC1 Inhibitor

open access: yesAdvanced Science, EarlyView.
We developed Affinity Selection Thin‐Layer Chromatography (AS‐TLC) as a method for high‐throughput screening (HTS) of compound mixtures. Furthermore, we integrated activity assays with AS‐TLC and identified a YTH domain‐containing protein 1 (YTHDC1) inhibitor. Building on this hit, we applied copper(I)‐catalyzed azide–alkyne cycloaddition (CuAAC) click
Mingchen Wang   +19 more
wiley   +1 more source

Restoration of m6A‐Modified circPSMB1 Suppresses Chordoma Progression and Enables Local Nanotherapeutic Intervention

open access: yesAdvanced Science, EarlyView.
An m6A‐modified circRNA, circPSMB1, is identified as a tumor suppressor in chordoma. METTL3‐dependent m6A promotes circPSMB1 interaction with HNRNPA2B1, limiting c‐MYC expression and malignant progression. An injectable HMnO2‐based nanohydrogel enables local circPSMB1 delivery and tumor microenvironment‐responsive therapy, offering a promising strategy
Yingchuang Tang   +7 more
wiley   +1 more source

Impaired Chaperone‐Mediated Autophagy Accelerates Intervertebral Disc Degeneration by Inducing MIDN Accumulation to Target TSC2 for Proteasomal Degradation

open access: yesAdvanced Science, EarlyView.
This graphical abstract illustrates how chaperone‐mediated autophagy (CMA) regulates intervertebral disc degeneration (IDD). Under normal homeostasis (B), CMA degrades cytoplasmic Midnolin (MIDN) to maintain proteostasis. Under inflammatory stress (A), impaired CMA leads to cytoplasmic MIDN accumulation.
Xianglong Chen   +9 more
wiley   +1 more source

DIXDC1 Promotes Lymphatic Metastasis and Resistance to Cuproptosis in Bladder Cancer Through Mediating DLAT

open access: yesAdvanced Science, EarlyView.
DIXDC1 drives bladder cancer progression by binding and stabilizing DLAT. This axis enhances NEK7 and CCNE2 mRNA stability to promote proliferation and lymphatic metastasis, while limiting copper‐induced DLAT oligomerization to reduce cuproptosis sensitivity, identifying DIXDC1 as a potential target linking metastasis with cuproptosis resistance ...
Hongqiong Li   +17 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

AARS1‐Mediated H3K27 Lactylation Rewires Glycolysis to Sustain Aggressive and Recurrent Bladder Cancer

open access: yesAdvanced Science, EarlyView.
AARS1 drives PI3K–AKT–mTOR‐dependent glycolysis in bladder cancer, promoting lactate accumulation, increased lactylation, H3K27la enrichment at the HK2 promoter, and HK2 transcription. HK2 reinforces glycolysis, sustaining a metabolic–epigenetic program associated with tumor progression, recurrence, and metastasis.
Qin Yuan   +13 more
wiley   +1 more source

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