Aqueous dispersions of lyotropic liquid crystalline phases (cubosomes and hexosomes) were prepared using lipid mixtures, monoolein (MO) and oleic acid (OA), and emulsifier Pluronic F127 by changing their composition. The size and internal structure of the prepared particles were characterized by dynamic light scattering and small-angle X-ray scattering, respectively. At the weight ratio of MO:OA ) 5:5 and 8 wt % F127 to the total lipid mixtures, particles with a diameter of ca. 140 nm and including an inverted hexagonal (HII) phase were formed. With an increase in the F127 concentration, the particle size decreased, but the internal structure (lattice constant) did not change, suggesting that F127 absorbs at the particle surface with little incorporation in the HII phase. The lipid ratios and solvent pH strongly affected the morphology of the internal structure of the particles. By increasing the weight fraction of OA in the lipid mixtures, the internal structure transformed in the order of bicontinuous cubic-inverted hexagonal-inverted cubic. In addition, transformation from the cubosome to the hexosome was observed by decreasing the pH, suggesting that the interior of the nanoparticles is responsive to the outer environment.

Samples of the carbonaceous asteroid Ryugu were brought to Earth by the Hayabusa2 spacecraft. We analyzed seventeen Ryugu samples measuring 1-8 mm. CO 2 -bearing water inclusions are present within a pyrrhotite crystal, indicating that Ryugu’s parent asteroid formed in the outer Solar System. The samples contain low abundances of materials that formed at high temperatures, such as chondrules and Ca, Al-rich inclusions. The samples are rich in phyllosilicates and carbonates, which formed by aqueous alteration reactions at low temperature, high pH, and water/rock ratios < 1 (by mass). Less altered fragments contain olivine, pyroxene, amorphous silicates, calcite, and phosphide. Numerical simulations, based on the mineralogical and physical properties of the samples, indicate Ryugu’s parent body formed ~ 2 million years after the beginning of Solar System formation.

Background-Aldosterone (ALD) has been shown to stimulate cardiac collagen synthesis and fibroblast proliferation via activation of local mineralocorticoid receptors. In patients with acute myocardial infarction, we demonstrated that ALD was extracted through the infarct heart and extracting ALD-stimulated post-infarct left ventricular (LV) remodeling. Methods and Results-To evaluate the effect of mineralocorticoid receptor antagonist (MRA) spironolactone on post-infarct LV remodeling, 134 patients with first anterior acute myocardial infarction were randomly divided into the MRA (nϭ65) or non-MRA (nϭ69) groups after revascularization. All patients were administered angiotensinconverting enzyme (ACE) inhibitor and study drug just after revascularization. Left ventriculography with contrast medium was performed at the acute stage and after 1 month to evaluate LV remodeling. ALD was measured at aortic root and coronary sinus. There was no difference in the baseline characteristics including infarct size and LV performance between the two groups. However, LV ejection fraction was significantly improved in the MRA group compared with that in the non-MRA group (46.0Ϯ0.6% to 53.2Ϯ0.8% versus 46.5Ϯ0.8% to 51.0Ϯ0.8%, P interaction ϭ0.012). LV end-diastolic volume index was significantly suppressed in the MRA group compared with that in non-MRA group (86.5Ϯ1.0 to 90.6Ϯ2.4 versus 87.5Ϯ1.3 to 106.8Ϯ3.5 mL/m 2 , P interaction ϭ0.002). Transcardiac extraction of ALD through the heart was significantly suppressed in the MRA group (P interaction ϭ0.001), and plasma procollagen type III aminoterminal peptide level, a biochemical marker of fibrosis, was significant lower in the MRA group compared with the non-MRA group (P interaction ϭ0.002). Conclusions-These findings indicate that MRA combined with ACE inhibitor can prevent post-infarct LV remodeling better than ACE inhibitor alone in association with the suppression of a marker of collagen synthesis. (Circulation.

The novel coronavirus, SARS-CoV-2, has been identified as the causative agent for the current coronavirus disease (COVID-19) pandemic. 3CL protease (3CL pro ) plays a pivotal role in the processing of viral polyproteins. We report peptidomimetic compounds with a unique benzothiazolyl ketone as a warhead group, which display potent activity against SARS-CoV-2 3CL pro . The most potent inhibitor YH-53 can strongly block the SARS-CoV-2 replication. X-ray structural analysis revealed that YH-53 establishes multiple hydrogen bond interactions with backbone amino acids and a covalent bond with the active site of 3CL pro . Further results from computational and experimental studies, including an in vitro absorption, distribution, metabolism, and excretion profile, in vivo pharmacokinetics, and metabolic analysis of YH-53 suggest that it has a high potential as a lead candidate to compete with COVID-19.