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ADSL promotes autophagy and tumor growth through fumarate-mediated Beclin1 dimethylation.
Nat Chem Biol
January 2025
Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
As an enzyme with a critical role in de novo purine synthesis, adenylosuccinate lyase (ADSL) expression is upregulated in various malignancies. However, whether ADSL possesses noncanonical functions that contribute to cancer progression remains poorly understood. Here, we demonstrate that protein kinase R-like endoplasmic reticulum kinase (PERK) activated by lipid deprivation or ER stress phosphorylates ADSL at S140, leading to an enhanced association between ADSL and Beclin1.
View Article and Find Full Text PDFMethanol transfer supports metabolic syntrophy between bacteria and archaea.
Nature
January 2025
Institute for Extra-Cutting-Edge Science and Technology Avant-Garde Research (X-star), Japan Agency for Marine-Earth Science and Technology (JAMSTEC), Yokosuka, Japan.
In subsurface methanogenic ecosystems, the ubiquity of methylated-compound-using archaea-methylotrophic methanogens-implies that methylated compounds have an important role in the ecology and carbon cycling of such habitats. However, the origin of these chemicals remains unclear as there are no known energy metabolisms that generate methylated compounds de novo as a major product. Here we identified an energy metabolism in the subsurface-derived thermophilic anaerobe Zhaonella formicivorans that catalyses the conversion of formate to methanol, thereby producing methanol without requiring methylated compounds as an input.
View Article and Find Full Text PDFAmyloid capture and aggregation inhibition by human serum albumin.
Int J Biol Macromol
January 2025
Departamento de Química Física, Facultade de Ciencias, Campus Terra, Universidade de Santiago de Compostela, 27002 Lugo, Spain. Electronic address:
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by amyloid-beta (Aβ) aggregation, primarily involving the peptides Aβ40 and Aβ42. Human serum albumin (HSA) has emerged as a potential therapeutic agent due to its ability to bind Aβ, inhibit aggregation, and promote disaggregation. This study quantitatively examined the interactions of HSA with both monomeric and aggregated forms of Aβ40 and Aβ42 using fluorescence techniques, including bulk steady-state fluorescence, fluorescence anisotropy, time-resolved fluorescence, and Fluorescence Correlation Spectroscopy (FCS).
View Article and Find Full Text PDFLerodalcibep and evolocumab for the treatment of homozygous familial hypercholesterolaemia with PCSK9 inhibition (LIBerate-HoFH): a phase 3, randomised, open-label, crossover, non-inferiority trial.
Lancet Diabetes Endocrinol
January 2025
LIB Therapeutics, Cincinnati, OH, USA. Electronic address:
Background: Lerodalcibep, a small binding anti-PCSK9 protein (adnectin), showed effective LDL cholesterol reduction in heterozygous familial hypercholesterolaemia. We aimed to assess the safety and efficacy of lerodalcibep and evolocumab in a globally diverse homozygous familial hypercholesterolaemia population.
Methods: This phase 3, randomised, open-label, crossover, non-inferiority study consisted of two 24-week treatment periods separated by an 8-week washout.
Invasive Lobular Carcinoma (ILC), a distinct subtype of breast cancer is hallmarked by E-Cadherin loss, slow proliferation, and strong hormone receptor positivity. ILC faces significant challenges in clinical management due to advanced stage at diagnosis, late recurrence, and development of resistance to endocrine therapy - a cornerstone of ILC treatment. To elucidate the mechanisms underlying endocrine resistance in ILC, ILC cell lines (MDA-MB-134-VI, SUM44PE) were generated to be resistant to tamoxifen, a selective estrogen receptor modulator.
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