Results 141 to 150 of about 21,644 (169)

A 3D In Vitro Model of the Human Hepatobiliary Junction

open access: yesAdvanced Science, EarlyView.
A 3D human organoid platform reconstructs the hepatobiliary junction between primary adult hepatocytes and intrahepatic cholangiocytes. These adult hepatobiliary organoids (aHBOs) support directional bile transport from canaliculi to ductule‐like structures, enable quantitative imaging of junction dynamics, and reveal cell‐type‐specific vulnerabilities
Ashley D. Westerfield   +13 more
wiley   +1 more source

Genome‐Wide CRISPR Screen Identifies a microRNA Orchestrating Pleiotropic Resistance to Targeted Therapy and T Cell Immunity in Melanoma

open access: yesAdvanced Science, EarlyView.
A genome‐wide microRNA CRISPR screen identifies miR‐18a as a master regulator of cross‐resistance in melanoma. Loss of miR‐18a activates the AJUBA–YAP/Hippo axis to confer BRAFi resistance and enhances THBS1–CD47 interaction to impair CD8+ T cell immunity. hnRNP A1 is identified as an upstream regulator of miR‐18a processing.
Zhao Wang   +19 more
wiley   +1 more source

Targeting Lactate and Lactylation in Cancer Metabolism and Immunotherapy

open access: yesAdvanced Science, EarlyView.
Lactate, once deemed a metabolic waste, emerges as a central regulator of cancer progression. This review elucidates how lactate and its epigenetic derivative, protein lactylation, orchestrate tumor metabolism, immune suppression, and therapeutic resistance.
Jiajing Gong   +5 more
wiley   +1 more source

Adipocyte‐Derived Leptolin Enhances Energy Expenditure and Prevents Obesity

open access: yesAdvanced Science, EarlyView.
We identified a novel adipokine, which we named leptolin. In humans, leptolin levels in white adipose tissue were positively correlated with exercise and negatively associated with body mass index. We observed elevated leptolin in serum from athletes and lower leptolin in serum from obese individuals.
Jiarui Liu   +17 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

Agnuside Stabilizes the Complex I Assembly Factor NDUFAF6 to Reinforce Mitochondrial Efficiency and Thermogenic Responsiveness

open access: yesAdvanced Science, EarlyView.
ABSTRACT Brown and beige adipocytes dissipate energy as heat, yet effective strategies to enhance their mitochondrial efficiency remain limited. Here, we identify Agnuside (AGN) as a selective stabilizer of the complex I assembly factor NDUFAF6. AGN directly binds cytosolic NDUFAF6, suppresses its ubiquitination, prolongs its half‐life, and facilitates
Qingwen Zhao   +7 more
wiley   +1 more source

PET Imaging of Cardiac Inflammation in Viral Myocarditis Using a DPP4‐Targeted Probe

open access: yesAdvanced Science, EarlyView.
This study describes a DPP4‐targeted PET probe for imaging myocardial inflammation by selectively targeting activated immune cells. Derived from the clinically approved small‐molecule inhibitor linagliptin, the probe demonstrates favorable biodistribution with specific cardiac uptake in myocarditis.
Wanhao Gao   +14 more
wiley   +1 more source

Enhanced Glycolysis‐Driven Histone H3K18 Lactylation Regulates Epileptogenesis by Modulating the E3 Ubiquitin Ligase COP1

open access: yesAdvanced Science, EarlyView.
Neuronal PKM2‐driven glycolysis generates excess lactate that triggers histone H3K18 lactylation (H3K18la), establishing a pathogenic metabolic‐epigenetic axis in epilepsy. Elevated H3K18la enriches the Cop1 promoter, transcriptionally upregulating the E3 ubiquitin ligase COP1, which subsequently drives proteasomal degradation of GABAARβ2 and impairs ...
Yuan Meng   +8 more
wiley   +1 more source

ZDHHC9‐Mediated Palmitoylation of ACSL4 Drives Ferroptosis in Diabetes Mellitus–Induced Erectile Dysfunction

open access: yesAdvanced Science, EarlyView.
ABSTRACT Diabetes mellitus‐induced erectile dysfunction (DMED) is a highly prevalent complication among diabetic patients; however, its underlying pathogenic mechanisms remain incompletely understood. Metabolic disorder is a hallmark of diabetes, yet its precise contribution to DMED progression is not well defined.
Wanyang Guo   +14 more
wiley   +1 more source
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