A robust nickel-catalyzed oxidative isocyanide insertion/C-H amination by reaction of readily available -uracil-amidines with isocyanides affording polysubstituted pyrimidouracils has been reported. The reaction proceeds in moderate to quantitative yield, under mild conditions (i.e., solvent, air atmosphere, moderate temperature). The broad range of structurally diverse isocyanides and -uracil-amidines that are tolerated make this method an interesting alternative to the currently available procedures toward pyrimidouracils.
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http://dx.doi.org/10.1021/acs.orglett.9b04387 | DOI Listing |
Neurosci Bull
January 2025
Center for Translational Neuromedicine and Neurology, School of Life Sciences, Institute for Brain Sciences Research, Henan University, Huaihe Hospital of Henan University, Kaifeng, 475004, China.
Parkinson's disease (PD), a chronic and common neurodegenerative disease, is characterized by the progressive loss of dopaminergic neurons in the dense part of the substantia nigra and abnormal aggregation of alpha-synuclein. Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by chronic insulin resistance and deficiency in insulin secretion. Extensive evidence has confirmed shared pathogenic mechanisms underlying PD and T2DM, such as oxidative stress caused by insulin resistance, mitochondrial dysfunction, inflammation, and disorders of energy metabolism.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Background: Microglia undergo varying regional dependent functional changes, which can exacerbate cognitive decline in Alzheimer's disease, but the full clinical relevance remains unclear. Ramified microglia survey the micro-environment and inert/amoeboid microglia engulf debris. A third morphological type; rod microglia, have been observed in a number of pathological conditions, but are relatively understudied.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of California, Irvine, Irvine, CA, USA.
Alzheimers Dement
December 2024
University of South Carolina School of Medicine, Columbia, SC, USA.
Background: The orexin/hypocretin neuropeptide system, primarily found in the lateral hypothalamus and perifornical region, modulates sleep, wakefulness, appetite, and cognitive function. One region with dense orexinergic projections is the basal forebrain (BF), which is the major source of acetylcholine in the neocortex and limbic structures such as the hippocampus. The basal forebrain cholinergic system mediates cognition and dysfunction is one of the key hallmarks of Alzheimer's disease.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Washington, School of Medicine, Seattle, WA, USA.
Background: Previously, we developed a co-calibrated and harmonized brain pathology score (BPS) across prospective cohort studies with research brain donation that incorporates multiple forms of postmortem neuropathology, using confirmatory factor analysis. We sought to identify genetic loci associated with BPS using a systems-biology approach, combining data from participants in the Adult Changes in Thought (ACT), the Religious Orders Study, and Rush Memory and Aging Project (ROSMAP) autopsy cohorts.
Method: We used PLINK in each cohort separately for genome-wide association studies (GWAS) of BPS using HRC imputed data from European ancestry participants, adjusting for age at death, sex, and population substructure.
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