Results 181 to 190 of about 470,712 (310)

Molecular Glue Degraders Enhance CAPRIN1‐Dependent Lysosomal Degradation of APP and Reduce Amyloid β in Alzheimer's Disease

open access: yesAdvanced Science, EarlyView.
A new class of lysosome‐directed molecular glue degraders selectively enhance CAPRIN1–APP interactions, driving APP degradation and reducing amyloid‐β production in human neurons and Alzheimer's disease mouse models. This CAPRIN1‐dependent targeted protein degradation strategy reveals a previously unrecognized therapeutic approach for disrupting the ...
Sunghan Jung   +15 more
wiley   +1 more source

TGFBI Maintains Fibrocartilage Homeostasis by Restraining O‐GlcNAcylation to Inactivate and Destabilize ADAMTS16 in Temporomandibular Joint Osteoarthritis

open access: yesAdvanced Science, EarlyView.
TGFBI deficiency elevates O‐GlcNAcylation, promoting the transcriptional activation of ADAMTS16 and OGT‐mediated post‐translational modification of ADAMTS16 at Ser1170. This leads to its stabilization and accumulation, driving chondrocyte metabolic disorders and senescent phenotypes, ultimately resulting in fibrocartilage dysfunction and TMJOA ...
Xin Liu   +12 more
wiley   +1 more source

TH/TRs–COL11A2 Axis Mediates Loss of a Differentiated Astrocyte State in Hypogyrified Brains

open access: yesAdvanced Science, EarlyView.
Using a gyrencephalic congenital hypothyroidism pig model, this study reveals cerebral atrophy and cortical hypogyrification. Single‐cell sequencing identifies astrocytes as major TH‐responsive cells, with the COL11A2‐enriched Astro‐2 state nearly absent.
Ying Zhang   +14 more
wiley   +1 more source

Ribonucleotides Amplify Mitochondrial DNA‐Driven cGAS–STING Activation via FdUMP‐ribonucleotide Hybrid Particles to Potentiate Chemoimmunotherapy

open access: yesAdvanced Science, EarlyView.
This work develops a metabolic sharing strategy that employs cytidine monophosphate (CMP) to competitively reprogram floxuridine (FUDR) pyrimidine metabolism in colorectal tumor cells. Elevated intracellular FdUMP induces nucleotide imbalance, drives mitochondrial DNA release and cGAS‐STING innate immune cascade activation, and potentiates robust ...
Chao Wang   +10 more
wiley   +1 more source

Distinct Cleavage Trajectories Mediated by DNA and RNA Substrate in Argonaute From Methanocaldococcus Fervens

open access: yesAdvanced Science, EarlyView.
This study characterizes MfAgo, an enzyme exhibiting highly efficient DNA‐guided DNA and RNA cleavage capability. Precise RNA cleavage strictly requires dimerization to stabilize the PIWI‐loop region, while its robust DNA cleavage functions in a dimerization‐independent manner.
Fuyong Huang   +9 more
wiley   +1 more source

Hierarchical Flux‐Protection Engineering Stabilizes Oxidation‐Prone Metabolic Nodes for High‐Level Curcumin Biosynthesis

open access: yesAdvanced Science, EarlyView.
Flux‐protection engineering stabilizes an oxidation‐prone L‐DOPA node in engineered E. coli by combining acid‐adapted chassis evolution, respiratory‐chain modulation, enzyme‐level flux matching, and pH–DO control. Carbon is redirected from oxidative browning to productive biosynthesis, enabling 1075.2 mg/L curcumin and demonstrating transferability to ...
Jianbin Chen   +10 more
wiley   +1 more source

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