Results 141 to 150 of about 173,415,106 (290)

A Hepatocyte‐to‐Stellate Cell Axis Couples Alternate‐Day Fasting to Liver Fibrosis Resolution via ATG7 S‐Nitrosylation

open access: yesAdvanced Science, EarlyView.
Alternate‐day fasting suppresses mitochondrial complex II assembly via SDHAF4 to upregulate hepatocyte eNOS. The resulting nitric oxide S‐nitrosylates ATG7 at C184 in hepatic stellate cells, restraining autophagic flux and preventing their profibrotic activation.
Xueqiang Wang   +17 more
wiley   +1 more source

Autism and mild epilepsy associated with a de novo missense pathogenic variant in the GTPase effector domain of DNM1

open access: yesAmerican Journal of Medical Genetics Part C: Seminars in Medical Genetics, EarlyView., 2023
Abstract Dynamin 1 is a GTPase protein involved in synaptic vesicle fission, which facilitates the exocytosis of neurotransmitters necessary for normal signaling. Pathogenic variants in the DNM1 gene are associated with intractable epilepsy, often manifested as infantile spasms at onset, developmental delay, and a movement disorder, and are located in ...
Davide Mei   +4 more
wiley   +1 more source

STING/Type I Interferon Pathway Activation Confers Multimodal Therapeutic Benefits in Osteomyelitis

open access: yesAdvanced Science, EarlyView.
STING/type I interferon signaling counteracts osteomyelitis through coordinated control of pain, bone destruction, and abscess formation. It inhibits pathogen‐induced nociceptor activation, restrains osteoclast‐mediated bone resorption, and suppresses IL‐1β‐driven neutrophil recruitment.
Yang Chen   +19 more
wiley   +1 more source

SPRED2 Negatively Regulates CD8+ T Cell‐Mediated Antitumor Immunity in Breast Cancer

open access: yesAdvanced Science, EarlyView.
Sprouty‑related EVH1 domain containing 2 (SPRED2) restrains Ras/Raf/ERK signaling in CD8+ T cells. Host SPRED2 deficiency enhances T‐cell survival, cytotoxicity, and memory‐like phenotypes, reducing primary tumor growth and endpoint lung metastatic burden in breast cancer models.
Miao Tian   +8 more
wiley   +1 more source

Drug Repurposing for Treating NCOR‐Related Intellectual Disability

open access: yesAdvanced Science, EarlyView.
An autism‐associated NCOR1 heterozygous mutation upregulates NRGs and activates NRG backward signaling in hypothalamic GABAergic neurons in mouse models, leading to Gabra2 downregulation and cognitive deficits, which can be therapeutically targeted by repurposing FDA‐approved drugs.
Yan Kong   +15 more
wiley   +1 more source

WFS1 Deficiency Impairs PIAS4‐Associated SUMOylation and Increases Ubiquitin‐Mediated Spermatogenesis‐Related Protein Degradation Leading to Testicular Male Infertility

open access: yesAdvanced Science, EarlyView.
The findings establish a critical role for WFS1 in human male fertility. Mechanistically, WFS1 interacts with PIAS4 to promote the SUMOylation of key spermatogenesis‐associated proteins, which in turn competitively inhibits their K48‐linked ubiquitin‐mediated degradation during spermatogenesis.
Yunchuan Tian   +14 more
wiley   +1 more source

NCOA4 Accelerates Abdominal Aortic Aneurysm Formation by Regulating Macrophage Activation and Ferroptosis via STAT1–CH25H Axis

open access: yesAdvanced Science, EarlyView.
Under pathological stimulation, NCOA4 in macrophages interacts with STAT1 to promote CH25H transcription. The subsequent increase in 25‐HC production activates macrophages, triggers inflammatory responses and ferroptosis, and accelerates the progression of AAA.
Zhinan Wu   +9 more
wiley   +1 more source

Structural Control of Stromal‐Immune Coupling by COL24A1 Underlies Pregnancy Maintenance

open access: yesAdvanced Science, EarlyView.
COL24A1 emerges as a collagen‐associated regulator of maternal‐fetal interface homeostasis. Its deficiency promotes a maladaptive TIMP1‐high stromal state, impaired ECM turnover, collagen accumulation, and stromal–immune dysregulation, contributing to pregnancy loss.
Teng Wu   +12 more
wiley   +1 more source

Inhibition of MEKK3 Prevents Cerebral Cavernous Malformation Progression Via Restoring Endothelial Integrity and Restricting Microglial Activation

open access: yesAdvanced Science, EarlyView.
In this study, we demonstrate that aberrant MEKK3 signaling in endothelial cells and microglia drives the progression of cerebral cavernous malformations (CCMs). Furthermore, we identify DPDH as a potent small‐molecule MEKK3 inhibitor with substantial therapeutic potential for CCM treatment.
Weiwei Zheng   +17 more
wiley   +1 more source

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