Results 171 to 180 of about 3,401 (261)

Pharmacological Inhibition of FKBP51 Mitigates Early Life Adversity‐Induced Social Deficits in Male Mice

open access: yesAdvanced Science, EarlyView.
Early life adversity triggers persistent social subordination and brain‐wide molecular dysregulation. Pharmacological inhibition of the stress‐mediator FKBP51 during the adversity period prevents these long‐term deficits and restores normative social hierarchy.
Joeri Bordes   +15 more
wiley   +1 more source

CREAT: A CRISPR‐Based Genome Trimming Strategy for Systematic Identification of Dispensable Regions and Rapid Genome Reduction

open access: yesAdvanced Science, EarlyView.
Current genome‐reduction methods work in a trial‐and‐error fashion, constituting a long‐standing bottleneck in the research. We developed CREAT (CRISPR‐based genome trimming with a multi‐homology‐arm template), a CRISPR‐based genetic approach that enables systematically classifying essential versus non‐essential genomic regions and subsequently ...
Guanhua Yuan   +7 more
wiley   +1 more source

Pemt Inhibition‐Mediated Vdac1 Oligomerization Regulates Mitochondrial Dysfunction, Apoptosis, and Inflammation in High‐Fat Diet‐Derived Liver Injury

open access: yesAdvanced Science, EarlyView.
ABSTRACT High‐fat diet (HFD)‐induced hepatic injury represents a pathology observed across vertebrates, yet the underlying mechanisms remain incompletely understood. Herein, the present study identifies phosphatidylethanolamine methyltransferase (Pemt), a key enzyme in phosphatidylcholine synthesis, as a critical regulator of mitochondrial homeostasis ...
Xianyong Bu   +11 more
wiley   +1 more source

Single‐Cell Reveal GALNT7‐Dependent Ferroptosis Suppression as a Mechanism of Immunotherapy Resistance in Non‐Small Cell Lung Cancer

open access: yesAdvanced Science, EarlyView.
Integrated clinical and mechanistic analyses identify GALNT7 as a ferroptosis‐suppressive regulator associated with immunotherapy resistance in non‐small cell lung cancer. GALNT7 depletion promotes lipid peroxidation, mitochondrial dysfunction, and ferroptosis, enhances CD8+ T‐cell activation and IFN‐γ production, and sensitizes tumors to PD‐1 blockade,
Jiadi Gan   +11 more
wiley   +1 more source

Mechanical Activation of Piezo1 Drives Osteoarthritis Through Kdm5c‐Mediated Epigenetic Silencing

open access: yesAdvanced Science, EarlyView.
Excessive mechanical stress activates Piezo1, triggering Ca2+‐dependent cytoskeletal forces that deform the nucleus and reduce H3K4me3. Kdm5c demethylates H3K4me3 at Col2a1 and Runx3 promoters. Kdm5c knockout rescues degradation. Repurposed telmisartan directly inhibits Kdm5c, blocking this axis and showing disease‐modifying efficacy in mouse OA models
Tianyou Kan   +13 more
wiley   +1 more source

Membrane Fusion‐Mediated Cytosolic Delivery of Threose Nucleic Acids via Homotypic Nanoparticles Overcomes Drug Resistance in Triple‐Negative Breast Cancer

open access: yesAdvanced Science, EarlyView.
This study introduces a biomimetic “nanofusion” platform that integrates the biostability of threose nucleic acids (TNA) with homotypic cell‐membrane cloaking to combat drug‐resistant TNBC. By leveraging a non‐canonical membrane‐fusion pathway for direct cytosolic delivery, the platform bypasses endosomal sequestration. To achieve potent AKT2 silencing
Wei Zheng   +7 more
wiley   +1 more source

Identification of a Nonribosomal Peptide Analog With Activity Against Multiple Gram‐Positive Bacteria via a Synthetic Bioinformatic Natural Product Discovery Approach

open access: yesAdvanced Science, EarlyView.
The genome of Rhodococcus erythropolis D‐1 was analyzed by bioinformatic tools to mine a novel nonribosomal peptide synthetase (NRPS) gene cluster. A nonribosomal peptide analog ZURJC5 associated with the NRPS was chemically synthesized. Through structure‐activity relationship studies, ZURJC28 was ultimately obtained and showed antibacterial activity ...
Keyi Chen   +9 more
wiley   +1 more source

Spatiotemporal Targeting Randle Cycle and Immune Checkpoint for Potent Antitumor Therapy

open access: yesAdvanced Science, EarlyView.
A glucose oxidase‐based nanogel (GOX‐NG) system using catechol‐functionalized alginate, exhibits enhanced tumor penetration, prolonged retention, and sustained glucose depletion in the tumor microenvironment. When combined with a fatty acid oxidation inhibitor, it implements dual metabolic suppression, thereby enhancing ROS‐induced immunogenic cell ...
Yuan Gao   +11 more
wiley   +1 more source

Ultrasound‐Activatable Piezoelectric Hydrogel Reprograms Mitochondrial Epigenetics for Osteoarthritis Therapy via the mTOR/GATD3A Axis

open access: yesAdvanced Science, EarlyView.
An ultrasound‐activatable piezoelectric hydrogel reprograms chondrocyte mitochondrial epigenetics via the mTOR/GATD3A axis, clearing damaged mitochondria and alleviating osteoarthritis progression in both mouse models and human cartilage explants. ABSTRACT The avascular nature of cartilage hinders drug delivery for osteoarthritis (OA) therapy.
Hui Zheng   +9 more
wiley   +1 more source

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