Results 141 to 150 of about 979,308 (296)

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

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

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

ECM‐Stiffness Mediated Persistent Fibroblast Activation Requires Integrin and Formin Dependent Chromatin Remodeling

open access: yesAdvanced Science, EarlyView.
Prolonged exposure to stiff extracellular matrix drives cancer‐associated fibroblasts into a persistently activated myofibroblast state. Two parallel pathways are identified: β1 integrin activation smoothens the nuclear lamina to reduce lamin–chromatin contacts, while the formin mDia2 regulates nuclear actin to alter chromatin organization.
Swathi Packirisamy   +4 more
wiley   +1 more source

DMAP1 Deficiency Suppresses Lung Cancer Progression by Destabilizing Replication Fork and Activating IFN Signaling‐Mediated Anti‐tumor Immunity

open access: yesAdvanced Science, EarlyView.
Lung cancer remains the leading cause of cancer‐related death. We investigated the role of the epigenetic regulator DMAP1 in NSCLC and found that its loss induces replication stress and DNA damage. This in turn activates type I IFN signaling via the cGAS–STING pathway and transcriptional ISG de‐repression, enhancing anti‐tumor immune responses ...
Kan Huang   +10 more
wiley   +1 more source

A Functionally Conserved Enhancer is Critical for PGC1A Expression and Thermogenesis in Brown Fat

open access: yesAdvanced Science, EarlyView.
An evolutionarily conserved enhancer controls PGC1A expression and thermogenic activation in brown adipose tissue. Integrative multi‐omics analyses identify two BAT‐specific enhancers, with PGC1A‐En1 functioning as the dominant regulatory element that maintains thermogenic capacity across species.
Duo Su   +10 more
wiley   +1 more source

CD4+ Tregs Drive Post‐Ischemic Sprouting Angiogenesis via Endothelial YY1/MAML1 Reactivation

open access: yesAdvanced Science, EarlyView.
ABSTRACT Microvascular complications of diabetes are chronic diseases of small vessels. We previously found that CD4+ regulatory T‐cells (Tregs) are markedly reduced in type 2 diabetes (T2D) after ischemic injury in both mice and humans, and that Treg deficiency in immunodeficient mice impairs vascular regeneration.
Hang Qu   +10 more
wiley   +1 more source

Hijacking the Host Clock: A Nematode Effector Antagonizes Soybean Circadian Defense and Translation Control

open access: yesAdvanced Science, EarlyView.
Soybean employs its circadian clock, governed by GmCCA1, to rhythmically defend against soybean cyst nematodes. The pathogen retaliates by secreting the effector Hg4E02, which hijacks the clock to suppress defense and co‐opt the host's translation machinery for nutrient acquisition.
Xingwei Wang   +21 more
wiley   +1 more source

Decoding IGLL5 Mutation‐Mediated BCR Signaling: A Novel Mechanism of CD8+ T Cell Exhaustion and Ocular MALT Lymphoma Progression

open access: yesAdvanced Science, EarlyView.
OAML harbors recurrent IGLL5 mutations that reinforce CD79A/CD79B‐associated BCR signaling. Mechanistic analysis of the S47G and A54G variants reveals induction of CXCL10/CXCL11, enhanced CD8+ T‐cell recruitment, and exhaustion‐associated dysfunction, supporting an immune‐tolerant niche.
Andi Zhao   +12 more
wiley   +1 more source

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