Exploring the reactivity of bicyclic α-iminophosphonates to access new imidazoline I receptor ligands.

Recent studies pointed out the modulation of imidazoline I receptors (I-IR) by selective ligands as a putative strategy to face neurodegenerative diseases. Foregoing the classical 2-imidazoline/imidazole-containing I-IR ligands, we report a family of bicyclic α-iminophosphonates endowed with high affinity and selectivity upon I-IR and we advanced a representative compound B06 in preclinical phases. In this paper, we describe the synthetic possibilities of bicyclic α-iminophosphonates by exploring its ambivalent reactivity, leading to unprecedented molecules that showed promising activities as I-IR ligands in human brain tissues and good BBB permeation capabilities.

Iodine-substituted hydroxyapatite nanoparticles and activation of derived ceramics for range verification in proton therapy.

Osteosarcoma is a radioresistant cancer, and proton therapy is a promising radiation alternative for treating cancer with the advantage of a high dose concentration in the tumor area. In this work, we propose the use of iodine-substituted hydroxyapatite (IHAP) nanomaterials to use iodine (I) as a proton radiation tracer, providing access to range verification studies in mineralized tissues. For this purpose, the nanomaterials were synthesized at four iodine concentrations hydrothermal synthesis.

First Exploration of Monopole-Driven Shell Evolution above the N=126 Shell Closure: New Millisecond Isomers in ^{213}Tl and ^{215}Tl.

Isomer spectroscopy of heavy neutron-rich nuclei beyond the N=126 closed shell has been performed for the first time at the Radioactive Isotope Beam Factory of the RIKEN Nishina Center. New millisecond isomers have been identified at low excitation energies, 985.3(19) keV in ^{213}Tl and 874(5) keV in ^{215}Tl.

BETA-HYDROXYBUTYRATE COUNTERACTS THE DELETERIOUS EFFECTS OF A SATURATED HIGH-FAT DIET ON SYNAPTIC AMPA RECEPTORS AND COGNITIVE PERFORMANCE.

The ketogenic diet, characterized by high fat and low carbohydrates, has gained popularity not only as a strategy for managing body weight but also for its efficacy in delaying cognitive decline associated with neurodegenerative diseases and the aging process. Since this dietary approach stimulates the liver's production of ketone bodies, primarily β-hydroxybutyrate (BHB), which serves as an alternative energy source for neurons, we investigated whether BHB could mitigate impaired AMPA receptor trafficking, synaptic dysfunction, and cognitive decline induced by metabolic challenges such as saturated fatty acids. Here, we observe that, in cultured primary cortical neurons, exposure to palmitic acid (200μM) decreased surface levels of glutamate GluA1-containing AMPA receptors, whereas unsaturated fatty acids, such as oleic acid and ω-3 docosahexaenoic acid (200μM), and BHB (5mM) increased them.