Results 161 to 170 of about 1,239,617 (330)

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

WDR72 Promotes Neuroblastoma Stemness and Progression by Sequestering TRIM31‐Mediated Degradation of CBX8

open access: yesAdvanced Science, EarlyView.
This study unveiled that METTL14 mediates m6A modification of WDR72 mRNA to stabilize and enhance WDR72 expression, which disrupts TRIM31‐mediated ubiquitination of CBX8 protein and retards its degradation, finally the elevated CBX8 contributes to tumor stemness.
Huijuan Zeng   +13 more
wiley   +1 more source

QRICH1 Disrupts Endoplasmic Reticulum Homeostasis and Amplifies NF‐κB Signaling in Periodontal Ligament Stem Cells to Exacerbate Diabetic Periodontitis

open access: yesAdvanced Science, EarlyView.
QRICH1 has been established as a key factor contributing to impaired osteogenic potential and accelerated apoptosis of PDLSCs in diabetic periodontitis. QRICH1 not only significantly enhances UPR‐associated apoptotic signaling but also amplifies NF‐κB‐mediated inflammatory responses. Its inhibition restores osteogenic capacity and reduces alveolar bone
Han Li   +9 more
wiley   +1 more source

Rewiring Pyroptosis to Potentiate Cancer Immunotherapy via a Gasdermin D Agonist Bypassing Caspase‐3

open access: yesAdvanced Science, EarlyView.
This work introduces a small‐molecule agonist, DIBDO, that bypasses Casp‐3 to directly trigger GSDMD‐mediated pyroptosis in tumors. Activated by glutathione, DIBDO generates singlet oxygen and molecular iodine, blocking Casp‐3 pathways and inducing immunogenic cell death.
Dan Zhao   +6 more
wiley   +1 more source

Spontaneous mutation rate [PDF]

open access: yesNature, 1991
DOUGLAS J. WINTON   +2 more
openaire   +3 more sources

Therapeutic Gene Editing of APOE4 in Sporadic Alzheimer's Disease via Prime Editor 7

open access: yesAdvanced Science, EarlyView.
Prime Editor 7‐mediated conversion of APOE4 to APOE3 alleviates Alzheimer's disease‐associated pathology in AD mouse models and patient‐derived neurons and improves cognitive performance in vivo, supporting therapeutic genome editing as a promising strategy for APOE4‐associated neurodegeneration.
Yunkyung Kim   +16 more
wiley   +1 more source

Identifying a Csmd3+ Microglial Subpopulation that Drives Cold‐to‐Hot Transition and Immune‐Cure in Glioblastoma

open access: yesAdvanced Science, EarlyView.
The study establishes an immune‐cure (ICu) mouse model based on a TMEMed G422TN‐GBM system that faithfully recapitulates human TMEMed GBM. scRNA‐seq analysis reveals a Csmd3+ microglial subset with innate immune memory (IIM) potential that potently suppresses GBM growth, drives a TME cold‐to‐hot transition, and induces 100% ICu in long‐term survival ...
Hai‐Feng Jiang   +12 more
wiley   +1 more source

A Unifying Thermodynamic Model for Phase Separation and Aging of Biopolymers

open access: yesAdvanced Science, EarlyView.
Phase separation and aging of intrinsically disordered proteins are placed in a unifying framework. A thermodynamically consistent time‐dependent version of associating‐polymer theory shows how the processes are intricately coupled. Assuming aging to occur through interacting sites resulting from reversible conformational transitions, the model ...
Jasper J. Michels   +2 more
wiley   +1 more source

Cancer‐Associated BCL‐2 Mutants Reveal Mechanisms Towards Venetoclax Resistance

open access: yesAdvanced Science, EarlyView.
Venetoclax (VEN) resistance in chronic lymphocytic leukemia arises from diverse BCL2 mutations. We map mechanisms contributing to VEN resistance across common BCL‐2 variants. G101V and D103Y reduce drug binding and increase sequestration of pro‐apoptotic proteins. V156D blocks VEN allosterically.
Jonas Aufdermauer   +9 more
wiley   +1 more source

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