Superconductivity of barium with highest transition temperatures in metallic materials at ambient pressure.

Pressure-induced superconductivity often occurs following structural transition under hydrostatic pressure (P) but disappears after the pressure is released. In the alkali-earth metal barium, superconductivity appears after structural transformation from body-centered cubic structure to hexagonal-close-packed (hcp) structure at P = 5 GPa, and the superconducting transition temperature (T) reaches a maximum of 5 K at P = 18 GPa. Furthermore, by stabilizing the low-temperature phase at P ~ 30 GPa, Tc reached a higher level of 8 K.

Efficacy of Naldemedine on Intestinal Hypomotility and Adhesions in Rodent Models of Postoperative Ileus.

Postoperative ileus (POI) often decreases patients' QOL because of prolonged hospitalization and readmission. Alvimopan, a peripheral μ-opioid receptor antagonist, is currently the only therapeutic drug for POI. The aim of this study was to examine the efficacy of naldemedine (a peripheral μ-opioid receptor antagonist with a non-competitive pharmacological profile different from that of alvimopan) on postoperative intestinal hypomotility and adhesion in rodent models, and compare it with the effects of alvimopan.

Discovery of NR2B-selective antagonists via scaffold hopping and pharmacokinetic profile optimization.

Selective N-methyl-d-aspartate receptor subunit 2B (NR2B) antagonists show potential as analgesic drugs, and do not cause side effects associated with non-selective N-methyl-d-aspartate (NMDA) antagonists. Using a scaffold-hopping approach, we previously identified isoxazole derivative 4 as a potent selective NR2B antagonist. In this study, further scaffold hopping of isoxazole derivative 4 and optimization of its pharmacokinetic profile led to the discovery of the orally bioavailable compound 6v.

Discovery of orally bioavailable cyclohexanol-based NR2B-selective NMDA receptor antagonists with analgesic activity utilizing a scaffold hopping approach.

NR2B subunit containing N-methyl-d-aspartate (NMDA) receptor is an attractive target for chronic pain due to its involvement in disease states and its limited distribution in the central nervous system. Cyclohexanol-based leads 6a and 6c were identified as potent NR2B-selective NMDA antagonists utilizing a scaffold hopping approach. Further optimization of this series through replacement of the amide in the leads with an isoxazole and efforts to optimize the pharmacokinetic profiles led to the discovery of orally available brain penetrants 7k and 7l, which demonstrated analgesic activity in the mouse formalin test at early and late phases.

Structure and polymorphisms of the major histocompatibility complex in the Oriental stork, Ciconia boyciana.

The major histocompatibility complex (MHC) is highly polymorphic and plays a central role in the vertebrate immune system. Despite its functional consistency, the MHC genomic structure differs substantially among organisms. In birds, the MHCs of Galliformes and the Japanese crested ibis (Pelecaniformes) are well-characterized, but information about other avian MHCs remains scarce.

SUMOylation regulates telomere length by targeting the shelterin subunit Tpz1(Tpp1) to modulate shelterin-Stn1 interaction in fission yeast.

Telomeres protect DNA ends of linear eukaryotic chromosomes from degradation and fusion, and ensure complete replication of the terminal DNA through recruitment of telomerase. The regulation of telomerase is a critical area of telomere research and includes cis regulation by the shelterin complex in mammals and fission yeast. We have identified a key component of this regulatory pathway as the SUMOylation [the covalent attachment of a small ubiquitin-like modifier (SUMO) to target proteins] of a shelterin subunit in fission yeast.

Acute intracerebroventricular administration of either carboxyl-terminal or amino-terminal fragments of agouti-related peptide produces a long-term decrease in energy expenditure in rats.

We investigated if agouti-related peptide (AgRP), an endogenous antagonist of melanocortin receptors (MC3-R and MC4-R), effects energy expenditure in rats. Fragments of the carboxyl-terminal, AgRP (83-132), and the amino-terminals, AgRP (25-51) and AgRP (54-82), were administered intracerebroventricularly (ICV). Food intake, body weight and fat weight changes were measured 5 and/or 24 h after a single ICV injection of the fragments.