Results 31 to 40 of about 167 (163)

Sortilin‐Mediated Rapid, Precise and Sustained Degradation of Membrane Proteins via mRNA‐Encoded Lysosome‐Targeting Chimera

open access: yesAdvanced Science, EarlyView.
The study identified sortilin as a promising LTR, enabling targeted degradation of oncogenic proteins through an mRNA‐encoded MedTAC strategy. In a mouse model, MedTACPTK7 reduced PTK7 by up to 80%, extended survival, and showed excellent pharmacokinetics without toxicity, providing a scalable platform for targeted therapies.
Xin Chang   +8 more
wiley   +1 more source

Functional Ambidexterity of an Ancient Nucleic Acid‐Binding Domain

open access: yesAngewandte Chemie, EarlyView.
The (HhH)2‐Fold is an ancient and ubiquitous nucleic acid‐binding domain. We demonstrate that this domain, which interacts with the minor groove of dsDNA, is functionally ambidextrous – that it can bind to dsDNA of either chirality. Moreover, binding of both chiral forms of dsDNA is mediated by an overlapping binding surface.
Orit Weil‐Ktorza   +8 more
wiley   +2 more sources

A Unique THN Motif Is Critical for Enabling Efficient C‐Terminal Traceless Cleavage

open access: yesAdvanced Science, EarlyView.
THN is identified as the key motif to facilitate the rapid traceless cleavage of gp41‐1. The deflection of THN motif not only avoids the interaction between C‐exteins and active sites, but also separates Asp107 away from Asn125. In addition, a flexible block F contributes to faster C‐cleavage.
Ruocheng Gu   +7 more
wiley   +1 more source

Inhibiting FAT1 Blocks Metabolic Bypass to Enhance Antitumor Efficacy of TCA Cycle Inhibition through Suppressing CPT1A‐Dependent Fatty Acid Oxidation

open access: yesAdvanced Science, EarlyView.
This study demonstrates that mutant FAT1 promotes ASCL2‐driven, CPT1A‐dependent fatty acid oxidation, leading to resistance to CPI‐613‐mediated TCA cycle inhibition in head and neck cancer. In vivo gene depletion of mutant FAT1 with LNP‐sgFAT1 suppresses tumor growth and restores CPI‐613 sensitivity, revealing a targetable metabolic bypass with ...
Fanghui Chen   +11 more
wiley   +1 more source

Structure and Antigenicity of Kaposi's Sarcoma‐Associated Herpesvirus Glycoprotein B

open access: yesAdvanced Science, EarlyView.
Kaposi's sarcoma‐associated herpesvirus (KSHV) causes severe cancers without effective treatments. This study presents an atomic model of KSHV's critical infection protein, gB, revealing a unique structure shared with related herpesviruses like Epstein‐Barr virus (EBV). The structural similarity highlights vulnerable targets for antibodies, guiding the
Xin‐Yan Fang   +8 more
wiley   +1 more source

DNA Origami‐Based CD44‐Targeted Therapy Silences Stat3 Enhances Cartilage Regeneration and Alleviates Osteoarthritis Progression

open access: yesAdvanced Science, EarlyView.
This study develops a cartilage‐targeted DNA origami system (OCS) that protects and delivers si‐Stat3 to chondrocytes. OCS reduces MMP13 expression, enhances extracellular matrix stability, and lowers oxidative stress while improving cell survival. In vivo, OCS decreases cartilage degradation biomarkers and promotes tissue repair factors, demonstrating
Qi Lv   +8 more
wiley   +1 more source

A Dual‐Targeting T6SS DNase Drives Bacterial Antagonism and Eukaryotic Apoptosis via the cGAS‐STING‐TNF Axis

open access: yesAdvanced Science, EarlyView.
The bacterial Type VI secretion system (T6SS) emerges as a sophisticated virulence mechanism, leveraging the dual‐function effector TkeA from Yersinia pseudotuberculosis. TkeA concurrently damages rival bacteria and host cell DNA, triggering the host's cGAS‐STING‐TNF pathway and inducing apoptosis.
Li Song   +13 more
wiley   +1 more source

Neutrophil‐Mimicking Nanomedicine Eliminates Tumor Intracellular Bacteria and Enhances Chemotherapy on Liver Metastasis of Colorectal Cancer

open access: yesAdvanced Science, EarlyView.
Fusobacterium nucleatum (Fn) enrichment has been identified in colorectal cancer and its liver metastases. This study develops neutrophil‐mimicking nanoparticles with multiple targeting capabilities encapsulating metronidazole and oxaliplatin for antibacterial and anticancer purposes. This approach reverses the epithelial mesenchymal transition process
Yanan Niu   +7 more
wiley   +1 more source

Microbial Biosensor for Sensing and Treatment of Intestinal Inflammation

open access: yesAdvanced Science, EarlyView.
The engineered calprotectin biosensor detects gut inflammation, processes the signal through genetic regulation, and responds by expressing the reporter sfGFP and the therapeutic protein secIL10. This dual functionality enables the engineered biosensor not only to sense but also to mitigate gut inflammation, highlighting its potential for disease ...
Duolong Zhu   +8 more
wiley   +1 more source

A Feedback Loop Between Fatty Acid Metabolism and Epigenetics in Clear Cell Renal Carcinoma

open access: yesAdvanced Science, EarlyView.
The current study has profiled the landscape of active enhancers in ccRCC and identified FABP5 as an oncogene. FABP5 is essential for the lipid droplet formation driven by HIFs and critical for H3K27ac and enhancer activity. The study has discovered the function of a feedback loop between epigenetics and lipid metabolism regulated by FABP5 in ccRCC ...
Zhou Ye   +21 more
wiley   +1 more source

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