Results 211 to 220 of about 23,156,384 (284)

Dual Role of Tamoxifen in Enhancing STING and CEACAM1 Expression to Prime a Favorable Tumor Microenvironment for Anti‐TIM3 Immunotherapy

open access: yesAdvanced Science, EarlyView.
Anti‐PD‐1/PD‐L1 blockade has revolutionized cancer immunotherapy, but is ineffective against endocrine‐treated (i.e., Tamoxifen), relapsed ER+ breast cancer (BC) patients. This study provides insight into the sub‐optimal response of ER+BCs to anti‐PD‐1/PD‐L1 blockade – highlighting the induction of STING and the CEACAM1/TIM3 axis after chronic ...
Marvin Angelo E Aberin   +20 more
wiley   +1 more source

Rab1A Promotes Hepatic Steatosis by Suppressing Mitophagy via the Raf‐1/ERK1/2/PINK1 Signaling Axis

open access: yesAdvanced Science, EarlyView.
Why does fat accumulate in the liver? Our study reveals Rab1A as the molecular switch that silences the cell's mitochondrial cleanup crew. Turning Rab1A off reactivates mitophagy, clears excess fat, and reverses fatty liver disease in mice—offering a promising new therapeutic target for MASLD, a growing global health challenge.
Li Zhang   +9 more
wiley   +1 more source

Gonadotropin‐Inhibitory Hormone (GnIH) and Its Receptor GPR147 Mediates Acute Stress‐Induced Activation of the Locus Coeruleus‐SAM Axis

open access: yesAdvanced Science, EarlyView.
ABSTRACT Gonadotropin‐inhibitory hormone (GnIH, also known as RFamide‐related peptide‐3, RFRP‐3) is a hypothalamic neuropeptide that regulates vertebrate reproduction via its receptor GPR147. Although GnIH is known to mediate stress‐induced reproductive suppression, its role in broader stress responses remains unclear.
Jiani Zhang   +18 more
wiley   +1 more source

Copper‐Driven Epithelial Barrier Disruption: A Novel Mechanism of COPD Acute Exacerbations Mediated by the TNF‐α/ATP7A Axis

open access: yesAdvanced Science, EarlyView.
This study reveals a copper‐driven mechanism of COPD acute exacerbations mediated by the TNF‐α/ATP7A axis. TNF‐α suppresses the copper transporter ATP7A via competitive NF‐κB/CREB1/CBP signaling, resulting in intracellular copper accumulation, mitochondrial oxidative stress, and epithelial barrier disruption.
Xinru Xiao   +7 more
wiley   +1 more source

An Adipocyte MKK3–p38β Axis Preserves Insulin Responsiveness in Mice and Is Reciprocally Altered in Human Obesity

open access: yesAdvanced Science, EarlyView.
The adipocyte MKK3–p38β axis emerges as an adaptive stress‐response pathway during obesity. Human visceral adipose tissue analyses, adipocyte‐specific mouse models, and primary adipocytes show that the MKK3–p38β axis supports insulin responsiveness by restraining p70S6K‐dependent inhibitory IRS1 feedback and preserving AKT–GLUT4 signaling. This pathway
Edgar Bernardo   +20 more
wiley   +1 more source

Transcription Factor Promiscuity Drives Regulatory Rewiring and Evolvability in Gene Networks in Bacteria

open access: yesAdvanced Science, EarlyView.
When a master transcription factor (TF) is lost, bacteria can rapidly rewire gene regulatory networks by co‐opting related regulators. Using experimental evolution in Pseudomonas fluorescens, we show that TF promiscuity (low‐level, non‐cognate binding) provides the raw material for rewiring. Successful co‐option follows a predictable hierarchy governed
Tiffany B. Taylor, Alan M. Rice
wiley   +1 more source

Phosphorylated STYK1 Promotes Gemcitabine Resistance via Autophagy‐Mediated Cancer Stemness in Pancreatic Cancer

open access: yesAdvanced Science, EarlyView.
Gemcitabine resistance remains a major challenge in pancreatic ductal adenocarcinoma. This study identifies STYK1 as a key mediator of chemoresistance through autophagy‐dependent maintenance of cancer stemness. Gemcitabine‐activated AMPK phosphorylates STYK1 at Ser91 and Ser304, enhancing autophagy and stemness.
Xueying Dong   +20 more
wiley   +1 more source

Disrupted TFEB/GDNF–cAMP/ATP Coupling Underlies Astrocytic Dysfunction and Depression in LRRK2 G2019S Parkinson's Mice

open access: yesAdvanced Science, EarlyView.
ABSTRACT The LRRK2 G2019S mutation, a Parkinson's disease–linked variant, has been associated with depression‐like phenotypes, but mechanisms remain unclear. We chart age‐dependent behavioral changes and astrocyte reactivity in G2019S mice and define a pathway connecting LRRK2 to TFEB/GDNF signaling, cellular energetics, and inflammation.
Longping Yao   +5 more
wiley   +1 more source

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