Results 91 to 100 of about 45,956 (217)

mTORC2 Phosphorylation of GSDME‐N Drives Cullin4B‐Mediated Proteasomal Degradation to Suppress Pyroptosis and Confer Radioresistance in Small Cell Lung Cancer

open access: yesAdvanced Science, EarlyView.
Radioresistance severely limits the efficacy of therapies for small cell lung cancer (SCLC). This study reveals a novel mechanism of resistance driven by the active suppression of pyroptosis. Specifically, the mTORC2 complex directly phosphorylates GSDME‐N and promotes its CUL4B‐mediated ubiquitination and proteasomal degradation.
Qing‐qing Xu   +11 more
wiley   +1 more source

Discovery and Engineering of a Rat Endogenous Retrovirus Reverse Transcriptase for Efficient Prime Editing

open access: yesAdvanced Science, EarlyView.
We screened 558 reverse transcriptases and engineered an optimized rat endogenous retrovirus‐derived variant, enRERV‐RT, via structure‐guided engineering and deep mutational scanning. This enhanced prime editor, based on the engineered RT, outperforms conventional M‐MLV‐RT systems across plant and animal cells, particularly at hard‐to‐edit loci ...
Linsha Ma   +22 more
wiley   +1 more source

A General Enzymatic Strategy for Site‐Specific Incorporation of Modified Genetic Building Blocks Into DNA

open access: yesAdvanced Science, EarlyView.
Eco‐friendly enzymatic synthesis of high‐fidelity, site‐specifically modified DNA using 3′‐blocked nucleotides for full synthetic control and next‐generation sequencing compatibility. ABSTRACT Methods for site‐specific incorporation of modified DNA building blocks remain limited.
Raveena Raveena   +2 more
wiley   +1 more source

Advances in CRISPR-Cas technology and its applications: revolutionising precision medicine

open access: yesFrontiers in Genome Editing
CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-associated proteins) has undergone marked advancements since its discovery as an adaptive immune system in bacteria and archaea, emerged as a potent gene-editing tool after the ...
Sarkar Sardar Azeez   +5 more
doaj   +1 more source

Cholesterol‐Mediated Metabolic‐mechanotransductive Crosstalk Orchestrates Castration Resistance in Prostate Cancer

open access: yesAdvanced Science, EarlyView.
Full androgen deprivation (FAD) induces paracrine cholesterol in prostate cancer that drives the polarization of cancer‐associated fibroblasts (CAFs) and subsequent elevated matrix stiffness. Matrix stiffness in turn potentiates tumor cell survival under FAD pressure via dual mechanotransductive activation of the IRE1α‐XBP1s stress‐response axis ...
Shaojie Liu   +20 more
wiley   +1 more source

Machine Learning‐Enhanced Ultrasensitive Immuno‐CRISPR Array Facilitates Early Diagnosis of Alzheimer's Disease by Detecting Multiple Plasma Biomarkers

open access: yesAdvanced Science, EarlyView.
This work presents a CRISPR‐based, ultrasensitive multiplex protein detection array capable of simultaneously analyzing six plasma biomarkers associated with Alzheimer's disease (AD). By integrating antibody‐mediated signal transduction, recombinase polymerase amplification, and spatially encoded CRISPR‐Cas12a, the system achieves detection sensitivity
Liding Zhang   +9 more
wiley   +1 more source

Targeting Lactate‐Driven Stromal Autophagy via MCT1 Disrupts the Immunosuppressive Niche and Sensitizes Pancreatic Cancer to PD‐1 Blockade

open access: yesAdvanced Science, EarlyView.
Tumor‐derived lactate activates PSCs through MCT1‐mediated Vps34 lactylation and autophagy. These activated PSCs secrete CXCL9/10, upregulating PD‐1 on CD8+ T cells via the CXCR3/STAT3 axis to foster immunosuppression. Disrupting this metabolic crosstalk by targeting MCT1 effectively sensitizes pancreatic cancer to PD‐1 blockade, presenting a promising
Wenfeng Zhuo   +14 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

Synergistic HMGN1 and VP64 Fusions Potentiate High‐Precision and PAM‐Flexible Base Editing

open access: yesAdvanced Science, EarlyView.
A novel CDA1Δ‐SpRY architecture fused with HMGN1 and VP64 yields a nearly PAM‐less base editing platform. By focusing cytosine conversion predominantly at position −18, this synergistic complex ensures highly precise targeting. Demonstrating enhanced efficiency across diverse models, including yeast and rice, the platform offers a robust solution for ...
Xi Luo   +11 more
wiley   +1 more source

The Spatiotemporal Genetic Architecture of Seed Vigor in Upland Cotton

open access: yesAdvanced Science, EarlyView.
Leveraging the semi‐automated SeedRanger platform, we profiled the germination kinetics of 356 cotton accessions at a 30‐min interval. This high‐throughput phenomic approach delineated a temporal genetic network comprising 541 stage‐specific loci. Crucially, functional validation identified FLA2 as a pivotal, auxin‐modulated regulator that orchestrates
Luyao Wang   +32 more
wiley   +1 more source

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