Results 211 to 220 of about 5,730,646 (258)

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

Targeted Degradation of Picornaviral 3C Protease via PROTACs Confers High Barrier to Viral Resistance and Broad‐Spectrum Antiviral Activity

open access: yesAdvanced Science, EarlyView.
This study reports D34 as the first PROTAC degrader that targets the 3C protease of picornaviruses. D34 effectively degrades EV71 3C protease via the ubiquitin‐proteasome pathway. More importantly, D34 exhibits a high resistance barrier and shows broad‐spectrum antiviral activity against multiple picornaviruses, highlighting its potential as a novel ...
Weilong Deng   +9 more
wiley   +1 more source

Reversing Temozolomide Resistance in Glioblastoma Based on Cuproptosis‐Mediated Positive Feedback Loop

open access: yesAdvanced Science, EarlyView.
To effectively reverse TMZ resistance, this work proposes a cuproptosis‐mediated positive feedback loop that integrates mitochondrial dysfunction, ATP depletion, AMPK‐p53 signaling, and glycolytic inhibition, ultimately amplifying cell death. This cuproptosis‐mediated feedback loop simultaneously disrupts multiple resistance pathways in GBM, including ...
Wenjie Feng   +9 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

A Second Pathogenic Protein, PolyGN2C‐iso2, Reveals a Dual‐Protein Pathology in Neuronal Intranuclear Inclusion Disease

open access: yesAdvanced Science, EarlyView.
This study reveals that NOTCH2NLC transcript variant 2 generates PolyGN2C‐iso2, an aggregating protein present within intranuclear inclusions of NIID patient tissues. A novel mouse model expressing PolyGN2C‐iso2 recapitulates white matter abnormalities and cognitive deficits, mechanistically linked to mitochondrial dysfunction. These findings support a
Kang Zhang   +22 more
wiley   +1 more source

Pyrazole‐Derived Antibacterial Compounds Effectively Treat Methicillin‐Resistant Staphylococcus Aureus Infections by Inhibiting Aspartate Transcarbamoylase

open access: yesAdvanced Science, EarlyView.
This study unveils a novel antibacterial mechanism against MRSA, in which the compound Py‐27 selectively targets and inhibits aspartate transcarbamoylase (ATCase), a key enzyme in pyrimidine synthesis. This inhibition disrupts DNA replication, induces oxidative damage, leading to potent bactericidal activity.
Xiaorong Yang   +11 more
wiley   +1 more source

Transposable Element–Driven PIEZO Mutation Enhances Locust Flight in Plateau Hypoxia

open access: yesAdvanced Science, EarlyView.
Why transposable elements (TEs) persisted or expanded in genomes remains a mystery. Using integrated analysis of TE macro‐ and microevolution in locusts, our results showed that thousands of TE insertions promoted widespread adaptive variation. Subfamilies of candidate adaptive TEs amplified and reshaped species‐level genomic architecture.
Xuanzhao Li   +8 more
wiley   +1 more source

O‐GlcNAcylation Regulation of SNAP29‐Dependent Autophagy Activation Dictates Chemoresistance in Gastric Cancer

open access: yesAdvanced Science, EarlyView.
Model illustrating the proposed mechanism by which chemotherapy‐induced downregulation of OGT disrupts SNAP29 O‐GlcNAcylation, promoting STX17‐SNAP29‐VAMP8 SNARE complex assembly and protective autophagy, leading to chemoresistance, which in turn establishes a feedforward loop to perpetuate drug tolerance.
Liang Tang   +9 more
wiley   +1 more source

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