Results 181 to 190 of about 262,733 (310)

Functional Mapping of Neurodevelopmental Disease Pathways to Key Neurodevelopmental Processes Represented in the Developmental Neurotoxicity In Vitro Testing Battery

open access: yesAdvanced Science, EarlyView.
Human‐relevant methods are essential for modern chemical safety assessment. This study helps define the capabilities and boundaries of an in vitro testing battery for developmental neurotoxicity by exploring its biological applicability domain. By linking neurodevelopmental disease‐related pathways to key neurodevelopmental processes, the work enhances
Eliska Kuchovska   +14 more
wiley   +1 more source

T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities

open access: yesAdvanced Science, EarlyView.
T cell exhaustion limits immunotherapy efficacy. This article delineates its progression from stem‐like to terminally exhausted states, governed by persistent antigen, transcription factors, epigenetics, and metabolism. It maps the exhaustion landscape in the TME and proposes integrated reversal strategies, providing a translational roadmap to overcome
Yang Yu   +7 more
wiley   +1 more source

An Activity‐Dependent NEPAS–PTX3 Axis Links Neurovascular and Myelin Deficits to Cognitive Impairment

open access: yesAdvanced Science, EarlyView.
An activity‐dependent pathway links prefrontal circuit hypoactivity to cognitive impairment. Reduced PVA–mPFC activity upregulates NEPAS, which suppresses PTX3 secretion, leading to impaired angiogenesis, myelin deficits, and memory decline. Rescue is achieved by NEPAS knockdown or chemogenetic circuit activation.
Boya Hu   +11 more
wiley   +1 more source

Genotype-phenotype characterization and functional reconstitution of pathogenic β-catenin variants from CTNNB1 syndrome patients.

open access: yesPLoS Genetics
Germline variants in the CTNNB1 gene, encoding β-catenin protein, cause severe neurodevelopmental alterations manifested early in the infancy, and define the CTNNB1 syndrome.
Caroline E Nunes-Xavier   +10 more
doaj   +1 more source

Hepatocyte BDNF Acts as a Novel Immune Checkpoint to Restrain TLR4‐Mediated Acute Hepatitis

open access: yesAdvanced Science, EarlyView.
This study identifies hepatocyte‐derived BDNF as an endogenous TLR4 antagonist that alleviates acute hepatitis. BDNF is downregulated in hepatocytes via REST‐mediated transcriptional repression during ALI/ALF. Mechanistically, BDNF binds to TLR4 on macrophages to suppress inflammation.
Weiwei Zhu   +15 more
wiley   +1 more source

FASLG Derived from Fibroblasts in Hydroxyapatite‐Rich Microenvironment Induces Urothelial Anoikis to Trigger Randall's Plaque Exposure

open access: yesAdvanced Science, EarlyView.
Randall's plaques (RP) serve as the nidus for calcium oxalate (CaOx) kidney stones. The current study reveals that hydroxyapatite (HAP) crystals activate the THY1–GSK3α/β–β‐catenin axis in renal interstitial fibroblasts (hRIFs), inducing FASLG secretion.
Minghui Liu   +14 more
wiley   +1 more source

In Vivo CRISPR Screening Identifies the Glutamate Receptor GRIA2 as Promoting Peritoneal Metastasis of Gastric Cancer via Calcium‐Dependent β‐Catenin Activation

open access: yesAdvanced Science, EarlyView.
We identified GRIA2 as a critical driver of gastric cancer peritoneal metastasis through in vivo CRISPR screening. Mechanistically, GRIA2‐mediated calcium influx inhibits GSK3β and activates Wnt/β‐catenin signaling, driven by glutamate from cancer‐associated fibroblasts.
Jie Sun   +13 more
wiley   +1 more source

ZMAT1 Promotes Osteoclastogenesis Through TRIM46 Mediated YAP1 Degradation and Inhibits Osteoblastogenesis

open access: yesAdvanced Science, EarlyView.
Zmat1 deficiency mitigates pathological bone loss by impairing osteoclastogenesis and promoting osteoblastogenesis. Mechanistically, in osteoclasts, Zmat1 loss relieves transcriptional repression of the E3 ligase TRIM46, promoting YAP1 degradation and inhibiting osteoclastogenic genes.
Xinyu Chang   +13 more
wiley   +1 more source

Promoter Hypermethylation‐Induced Silencing of FXYD1 Drives Breast Cancer Metastasis via DDX5‐Mediated Wnt/β‐Catenin Pathway Activation

open access: yesAdvanced Science, EarlyView.
This study identifies FXYD1 as an epigenetically silenced tumor suppressor in breast cancer. DNA methylation turns off the gene FXYD1 in breast cancer, and low levels predict worse outcomes. Restoring FXYD1 limits breast cancer cells proliferation and metastasis. In the nucleus, FXYD1 recruits the E3 ligase MAEA to K63‐ubiquitinate DDX5 for proteasomal
Ping Wen   +11 more
wiley   +1 more source

Tumor‐Derived Exosomal TAGLN2 Promotes Metastasis by Inducing Vascular Permeability and Angiogenesis via the NRP1/SEMA4D/YAP Axis

open access: yesAdvanced Science, EarlyView.
Gastric cancer‐derived exosomal TAGLN2 is identified as a key mediator of vascular reprogramming, with significantly elevated levels detected in patient serum. Independent of canonical SEMA4D signaling, it nucleates a cytoplasmic TAGLN2/NRP1/SEMA4D ternary complex that dually activates YAP, promoting angiogenesis, vascular dysfunction, and metastasis ...
Shuqi Yu   +7 more
wiley   +1 more source

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