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Silver-Catalyzed Cascade Radical Isonitrile Insertion/Defluorinative Cyclization: Direct Synthesis of 4-CFH-2-Phosphinoyl-quinolines.
J Org Chem
January 2025
Faculty of Science, Kunming University of Science and Technology, Jingming South Road 727, Chenggong District, Kunming 650500, P. R. China.
A novel silver-catalyzed cascade radical isonitrile insertion and defluorinative cyclization have been developed to synthesize CFH- and phosphinoyl-containing quinolines from -isocyanyl α-trifluoromethylstyrenes. The reaction proceeded under redox-neutral conditions and allowed the construction of a highly attractive quinoline ring system, with the simultaneous formation of the CFH group and introduction of various phosphinoyl groups in a single transformation, showing operational simplicity, a wide substrate scope, good tolerance for functional groups, and remarkable atom-/stepeconomy. Mechanistic studies indicated that the reaction is likely to involve the participation of P-centered radicals and key carbanion intermediates.
View Article and Find Full Text PDFSex Affects Cognitive Outcomes in HIV-1 Tat Transgenic Mice: Role of CCR5.
ASN Neuro
January 2025
Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, Virginia, USA.
People living with HIV (PLWH) experience HIV-associated neurocognitive disorders (HAND), even though combination antiretroviral therapy (cART) suppresses HIV replication. HIV-1 transactivator of transcription (HIV-1 Tat) contributes to the development of HAND through neuroinflammatory and neurotoxic mechanisms. C-C chemokine 5 receptor (CCR5) is important in immune cell targeting and is a co-receptor for HIV viral entry into CD4+ cells.
View Article and Find Full Text PDFODSEI Chip: An Open 3D Microfluidic Platform for Studying Tumor Spheroid-Endothelial Interactions.
Adv Sci (Weinh)
January 2025
Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, South Korea.
Current in vitro models of 3D tumor spheroids within the microenvironment have emerged as promising tools for understanding tumor progression and potential drug responses. However, creating spheroids with functional vasculature remains challenging in a controlled and high-throughput manner. Herein, a novel open 3D-microarray platform is presented for a spheroid-endothelium interaction (ODSEI) chip, capable of arraying more than 1000 spheroids on top of the vasculature, compartmentalized for single spheroid-level analysis of drug resistance, and allows for the extraction of specific spheroids for further analysis.
View Article and Find Full Text PDFMA Demethyltransferase FTO Attenuates Meniscus Degeneration and Osteoarthritis via Orchestrating Autophagy and Energetic Metabolism.
Adv Sci (Weinh)
January 2025
Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.
Impaired autophagy is reported to promote osteoarthritis (OA). However, the mechanism by which autophagy in regulating meniscus degeneration and OA remains unclear. Here, unconvered aberrant energetic metabolism pattern in meniscus cells with OA is uncovered first, which results in lower adenosine triphosphate (ATP) production.
View Article and Find Full Text PDFImpact of sex hormones on pheochromocytomas, paragangliomas, and gastroenteropancreatic neuroendocrine tumors.
Eur J Endocrinol
January 2025
Department of Internal Medicine IV, LMU University Hospital, LMU Munich, 80336 Munich, Germany.
Objective: The effects of sex hormones remain largely unexplored in pheochromocytomas and paragangliomas (PPGLs) and gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
Methods: We evaluated the effects of estradiol, progesterone, Dehydroepiandrosterone sulfate (DHEAS), and testosterone on human patient-derived PPGL/GEP-NET primary culture cell viability (n = 38/n = 12), performed next-generation sequencing and immunohistochemical hormone receptor analysis in patient-derived PPGL tumor tissues (n = 36).
Results: In PPGLs, estradiol and progesterone (1 µm) demonstrated overall significant antitumor effects with the strongest efficacy in PPGLs with NF1 (cluster 2) pathogenic variants.
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