Results 101 to 110 of about 252,850 (254)

DOT1L Drives Endothelial‐to‐Mesenchymal Transition and Fibrotic Vascular Remodeling via H3K79 Methylation

open access: yesAdvanced Science, EarlyView.
DOT1L as a central epigenetic regulator of EndoMT and pulmonary fibrosis. Acting as an early epigenetic switch, it translates TGFβ–SMAD signaling into H3K79me2‐mediated chromatin remodeling, selectively activates fibrosis‐related genes, and primes ECs for rapid mesenchymal transition.
Yaofeng Wang   +11 more
wiley   +1 more source

Deciphering and Targeting the Schwannoma‐Neuron‐Macrophage Crosstalk for the Treatment of Schwannomatosis and Associated Pain

open access: yesAdvanced Science, EarlyView.
We established patient‐derived SWN cell lines and orthotopic PDX models that recapitulate patient pain phenotypes, alongside a novel intravital DRG imaging platform to track macrophage infiltration and neuronal pain responses. Using these models, we define HMGB1–CCL2–IL‐6 signaling crosstalk driving pain and identify EGF signaling as a key regulator of
Zhenzhen Yin   +17 more
wiley   +1 more source

A Testis‐Specific Aralkylamine N‐Acetyltransferase Regulates Dimorphic Sperm Function and Male Fertility in Moths

open access: yesAdvanced Science, EarlyView.
We identify a Lepidoptera‐conserved testis‐specific arylalkylamine N‐acetyltransferase (LTNAT) that governs male moth fertility via a novel mechanism. LTNAT loss disrupts eupyrene sperm mitochondrial derivatives and impairs apyrene sperm motility, offering a safe molecular target for innovative pesticides and genetic pest control.
Hao Sun   +5 more
wiley   +1 more source

Targeting the PDK1/c‐Myc/SOX10 Signaling in Oligodendrocytes Alleviates Neuropathic Pain

open access: yesAdvanced Science, EarlyView.
This work reveals that oligodendrocyte homeostasis, mediated by PDK1, is a critical determinant of neuropathic pain (NPP) pathogenesis. Disruption of PDK1 in oligodendrocytes impairs SOX10‐dependent myelination programs through c‐Myc accumulation, leading to disrupted myelination and the pathophysiology of NPP.
Pingping Qiao   +7 more
wiley   +1 more source

Upregulated SK2 Expression and Impaired CaMKII Phosphorylation Are Shared Synaptic Defects Between 16p11.2del and 129S: Mutant Mice

open access: yesASN Neuro, 2018
Ion channel gating and kinase regulation of N-methyl-D-aspartate receptor 1 activity are fundamental mechanisms that govern synaptic plasticity. In this study, we showed that two mutant models (16p11.2del and Δdisc1 ) that recapitulate aspects of human ...
Razia Sultana   +4 more
doaj   +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

Transgenic fatal familial insomnia mice indicate prion infectivity-independent mechanisms of pathogenesis and phenotypic expression of disease.

open access: yesPLoS Pathogens, 2015
Fatal familial insomnia (FFI) and a genetic form of Creutzfeldt-Jakob disease (CJD178) are clinically different prion disorders linked to the D178N prion protein (PrP) mutation.
Ihssane Bouybayoune   +20 more
doaj   +1 more source

Cryo‐EM Structure Guided Engineering of Botulinum Neurotoxin A With Advanced Receptor Binding Affinity and Therapeutical Benefits

open access: yesAdvanced Science, EarlyView.
The butterfly unfolded wing in an open form structure of botulinum neurotoxin type A (BoNT/A) at physiological‐state was confirmed at 2.85 Å resolution by cryo‐electron microscopy (cryo‐EM). Structure‐guided protein engineering significantly enhanced the receptor‐binding affinity, therapeutic efficacy, and safety of the engineered toxin variants ...
Wenrui Wang   +16 more
wiley   +1 more source

GPCRs in CAR‐T Cell Immunotherapy: Expanding the Target Landscape and Enhancing Therapeutic Efficacy

open access: yesAdvanced Science, EarlyView.
Chimeric antigen receptor T cell therapy faces dual challenges of target scarcity and an immunosuppressive microenvironment in solid tumors. This review highlights how G protein‐coupled receptors can serve as both novel targets to expand the therapeutic scope and functional modules to enhance CAR‐T cell efficacy.
Zhuoqun Liu   +11 more
wiley   +1 more source

Gemella morbillorum Promotes Colorectal Carcinogenesis: LPBDCP‐Mediated Invasion Activates Ras Signaling and Destabilizes p53

open access: yesAdvanced Science, EarlyView.
ABSTRACT Gut microbiota dysbiosis promotes colorectal cancer (CRC) tumorigenesis. A global fecal metagenomic analysis identified Gemella morbillorum as a key contributor to the CRC‐associated microbiota. Fluorescence in situ hybridization revealed that Gemella morbillorum is enriched in CRC tumor tissues compared to adjacent normal tissues.
Zhen Wang   +8 more
wiley   +1 more source

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