Results 221 to 230 of about 2,979,740 (254)

Temporal Trajectories of the Tau Aggregate Interactome Reveal Stage‐Specific Vulnerabilities in Alzheimer's Disease

open access: yesAdvanced Science, EarlyView.
Tau populations with different aggregation states associate with distinct sets of proteins in the Alzheimer's disease brain. Proteomic discovery combined with single‐molecule analysis in neurons reveals dynamic associations involving proteostasis, metabolism and RNA biology.
Dorothea Böken   +8 more
wiley   +1 more source

A Hepatocyte‐to‐Stellate Cell Axis Couples Alternate‐Day Fasting to Liver Fibrosis Resolution via ATG7 S‐Nitrosylation

open access: yesAdvanced Science, EarlyView.
Alternate‐day fasting suppresses mitochondrial complex II assembly via SDHAF4 to upregulate hepatocyte eNOS. The resulting nitric oxide S‐nitrosylates ATG7 at C184 in hepatic stellate cells, restraining autophagic flux and preventing their profibrotic activation.
Xueqiang Wang   +17 more
wiley   +1 more source

Puerarin‑Loaded pH‑Responsive ZIF‑90 Nanoparticles Ameliorate Osteoporosis via Enhancing H3K18 Lactylation and Suppressing Aberrant Osteoclast Activation

open access: yesAdvanced Science, EarlyView.
Schematic illustration of the mechanism by which ZIF‐90@PU alleviates osteoporosis via H3K18la‐mediated NFATc1 pathway suppression. ABSTRACT Osteoporosis is characterized by dysregulated osteoclast activity, leading to excessive bone resorption and structural damage.
Jiajia Lu   +5 more
wiley   +1 more source

FBP1‐Mediated Compartmentalization of Glycolytic Enzyme Complexes Suppresses PKM2 Function to Ameliorate MASLD Progression

open access: yesAdvanced Science, EarlyView.
In normal hepatocytes, FBP1 forms compartmentalized complexes with PKM2, ENO1, and LDHA independent of its catalytic activity, inhibiting PKM2 activity and restricting excessive glycolysis. During MASLD progression, FBP1 downregulation markedly reduces the abundance of these complexes and releases the “hijacked” glycolytic enzymes, leading to PKM2 ...
Busong Wang   +10 more
wiley   +1 more source

NS1‐Induced PARP1 Phase Transitions Prolongs Host Transcriptional Pausing to Promote Influenza A Virus Replication

open access: yesAdvanced Science, EarlyView.
After IAV infection, NS1 induces PARP1 phase transition, reducing molecular mobility in condensates, prolonging host transcriptional pause, aiding RdRp cap snatching, and promoting viral transcription. ABSTRACT Influenza A virus (IAV) commandeers host transcriptional machinery to replicate, but mechanisms remain elusive.
Shufeng Ma   +12 more
wiley   +1 more source

Retrospective Grid Cells in the Medial Entorhinal Cortex Encode Past Paths During Spatial Navigation

open access: yesAdvanced Science, EarlyView.
Retrospective grid cells are identified in the medial entorhinal cortex, with spatial firing patterns that become most grid‐like when activity is projected onto recently traversed locations. Their coding loses spatial precision in darkness and is disrupted during assisted movement, indicating that entorhinal representations incorporate recent path ...
Ruojin Liu   +10 more
wiley   +1 more source

Tracking CDK1 Dynamics With a Novel Biosensor Mouse and Clinical Cohorts to Predict CDK4/6 Inhibitor Sensitivity in ER+ Breast Cancer

open access: yesAdvanced Science, EarlyView.
Cyclin‐dependent kinase (CDK) 1 activity is a dynamic marker of treatment response in estrogen receptor positive breast cancer. Patient cohorts reveal CDK1 activity increases during progression to invasive disease, where high expression correlates with poor survival. Using a novel Cdk1 biosensor mouse alongside in vitro models, we demonstrate that CDK1
Sarah Alexandrou   +17 more
wiley   +1 more source

Degrading GPX4 via Biomimetic Nanoparticle‐Mediated In Situ Synthesis of Deep‐Learning‐Designed Binder‐Degron Chimeras for Prostate Cancer Therapy

open access: yesAdvanced Science, EarlyView.
A deep‐learning‐designed binder is fused to a combinatorial degron to create a binder‐degron chimera (bdC) that recruits the CUL2‐RING ubiquitin ligase complex. Encapsulation in a prostate‐cancer‐targeted, CD47‐camouflaged nanocarrier enables tumor‐specific in situ bdC expression, triggering GPX4 degradation and ferroptosis, thereby establishing a ...
Si‐Han Zhang   +8 more
wiley   +1 more source

Engineered Peptide Self‐Assembled Nanofibers for Enhanced STING Activation: A Promising Nanodelivery Platform for Immunotherapy of Pediatric Solid Tumors

open access: yesAdvanced Science, EarlyView.
An engineered peptide self‐assembled nanofiber platform, designed to replicate STING–cGAMP binding motifs, facilitates pH‐responsive cytosolic delivery of cGAMP, enhances the endoplasmic reticulum with high efficiency, and robustly activates the STING pathway.
Yubin He   +6 more
wiley   +1 more source

Targeted‐Penetrating Biomimetic Hybrid Transfersomes for Enhanced Transdermal Gene Transfection in Hypertrophic Scar Therapy

open access: yesAdvanced Science, EarlyView.
Hypertrophic scar fibroblasts membrane‐hybridized cationic transfersomes enable efficient loading and transdermal delivery of TGF‐β1 siRNA through multiple skin penetration pathways. The biomimetic platform enhances homotypic targeting, transfection, and immune evasion, suppresses TGF‐β1‐driven fibrotic signaling, and reduces extracellular matrix ...
Hui Xing   +9 more
wiley   +1 more source

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