Results 141 to 150 of about 222,321 (300)

Discovery of H2 Receptor Antagonists as Colistin Enhancers by Targeting Acid Stress Response

open access: yesAdvanced Science, EarlyView.
This study identifies YqgB as a key target for restoring colistin susceptibility in mcr‐positive pathogens under acidic conditions by remodeling phospholipid composition and reducing LPS modification. Deep learning‐based screening reveals H2 receptor antagonists as novel colistin adjuvants. Further investigations indicate that ranitidine and famotidine
Jinju Cai   +7 more
wiley   +1 more source

Paternal Circadian Disruption Impairs Offspring Cognition via Sperm microRNAs

open access: yesAdvanced Science, EarlyView.
Paternal circadian disruption remodels the sperm small RNA payload, elevating miR‐92a‐3p/miR‐25‐3p levels and perturbing early embryonic gene regulatory programs. Microinjection experiments and single‐embryo transcriptomics reveal sex‐specific developmental vulnerabilities, ultimately impairing offspring hippocampal synaptic plasticity and cognition ...
Kexin Zou   +22 more
wiley   +1 more source

Zinc Exposure Causes Disulfidptosis to Induce Miscarriage by Up‐Regulating GATA1/METTL1/SLC7A11 Axis

open access: yesAdvanced Science, EarlyView.
Zn exposure up‐regulates GATA1, promoting GATA1‐mediated METTL1 and SLC7A11 transcription. It also enhances METTL1‐mediated m7G modification on SLC7A11 mRNA, increasing SLC7A11 mRNA stability. Ultimately, Zn exposure up‐regulates SLC7A11 at both transcriptional and post‐transcriptional levels, causing disulfidptosis. Knockdown of murine Slc7a11, Gata1,
Wenxin Huang   +16 more
wiley   +1 more source

Neuid: A Novel Neuron‐Enriched LncRNA that Connects Epigenetic Gene Silencing to Alzheimer's Disease

open access: yesAdvanced Science, EarlyView.
ABSTRACT The increasing evidence that non‐coding RNAs can become deregulated during pathogenesis is dramatically expanding the space for drug discovery beyond the protein‐coding genome. Long noncoding RNAs (lncRNAs) are emerging as key regulators of cellular function, yet most remain uncharacterized.
Ranjit Pradhan   +17 more
wiley   +1 more source

De Novo Design and Directed Evolution Refinement of Mirror‐Image Protein Binders Targeting Interleukin‐4

open access: yesAdvanced Science, EarlyView.
This study presents the de novo design and directed evolution of a mirror‐image D‐protein inhibitor targeting human interleukin‐4 (IL‐4). The engineered molecule exhibits nanomolar binding affinity for IL‐4 and effectively inhibits IL‐4–mediated signaling.
Liqing Xu   +7 more
wiley   +1 more source

Understanding and Overcoming Antibody‐Drug Conjugate Resistance: Biological Mechanisms and Emerging Analytical Frameworks in Breast Cancer

open access: yesAdvanced Science, EarlyView.
Antibody–drug conjugates (ADCs) transform breast cancer therapy, yet resistance limits their durability. Emerging evidence reveals that ADC failure is not solely tumor‐intrinsic but shaped by dynamic tumor–microenvironment interactions that alter drug delivery, processing, and response.
Minji Seo, Jangsoon Lee, Naoto T. Ueno
wiley   +1 more source

Size‐Modulated Mesoderm‐Endoderm Divergence and Myocardial Cavitation in Micropatterned Cardioids

open access: yesAdvanced Science, EarlyView.
Micropatterned cardioids, CRISPR‐engineered reporter hiPSCs, deep‐tissue imaging, and single‐cell RNA sequencing are integrated to model mesoderm‐endoderm co‐development. Heart‐foregut crosstalk promotes single large cavitation inside cardioids, resembling early heart chamber formation. ABSTRACT The human heart, originating from the splanchnic mesoderm,
Plansky Hoang   +12 more
wiley   +1 more source

Halofuginone is a Molecular Glue Degrader of Integrin β4

open access: yesAdvanced Science, EarlyView.
Integrin β4 overexpression is linked to aggressive tumors and poor prognosis, but targeted therapies are lacking. We identified halofuginone (HF) as a molecular glue degrader that promotes integrin β4 degradation via the CRL4BWDR18 E3 ligase. HF suppresses tumor progression in vitro and in vivo, offering a new strategy for targeting oncogenic ...
Wei Gong   +8 more
wiley   +1 more source

GNL3 Orchestrates AR Transcriptional Programs to Drive Castration‐Resistant Prostate Cancer and Immune Evasion

open access: yesAdvanced Science, EarlyView.
GNL3 is a novel AR coregulator with dual coactivator and corepressor functions in prostate cancer (PCa). Our study uncovers a previously unrecognized mechanism by which the AR transcriptional complex integrates oncogenic signaling and immune suppression.
Cuiting Zhang   +12 more
wiley   +1 more source

ETV4 Promotes Colorectal Cancer Progression by Reprogramming Asparagine Metabolism to Remodel the Stromal Microenvironment

open access: yesAdvanced Science, EarlyView.
ETV4 coordinates a dual transcriptional program by upregulating MET and asparagine synthetase (ASNS). The resulting asparagine (Asn) secretion acts as a metabolic signal, reprogramming hepatic stellate cells (HSCs) and primary cancer‐associated fibroblasts (CAFs) toward an inflammatory phenotype. These activated stromal cells release HGF to sustain the
Dujiang Fu   +14 more
wiley   +1 more source

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