Impact of cardiac support device combined with slow-release prostacyclin agonist in a canine ischemic cardiomyopathy model

BackgroundThe cardiac support device supports the heart and mechanically reduces left ventricular (LV) diastolic wall stress. Although it has been shown to halt LV remodeling in dilated cardiomyopathy, its therapeutic efficacy is limited by its lack of biological effects. In contrast, the slow-release synthetic prostacyclin agonist ONO-1301 enhances reversal of LV remodeling through biological mechanisms such as angiogenesis and attenuation of fibrosis. We therefore hypothesized that ONO-1301 plus a cardiac support device might be beneficial for the treatment of ischemic cardiomyopathy.MethodsTwenty-four dogs with induced anterior wall infarction were assigned randomly to 1 of 4 groups at 1 week postinfarction as follows: cardiac support device alone, cardiac support device plus ONO-1301 (hybrid therapy), ONO-1301 alone, or sham control.ResultsAt 8 weeks post-infarction, LV wall stress was reduced significantly in the hybrid therapy group compared with the other groups. Myocardial blood flow, measured by positron emission tomography, and vascular density were significantly higher in the hybrid therapy group compared with the cardiac support device alone and sham groups. The hybrid therapy group also showed the least interstitial fibrosis, the greatest recovery of LV systolic and diastolic functions, assessed by multidetector computed tomography and cardiac catheterization, and the lowest plasma N-terminal pro-B-type natriuretic peptide levels (P < .05).ConclusionsThe combination of a cardiac support device and the prostacyclin agonist ONO-1301 elicited a greater reversal of LV remodeling than either treatment alone, suggesting the potential of this hybrid therapy for the clinical treatment of ischemia-induced heart failure

Solution structure and dynamics of mouse ARMET

AbstractARMET is an endoplasmic reticulum (ER) stress-inducible protein that is required for maintaining cell viability under ER stress conditions. However, the exact molecular mechanisms by which ARMET protects cells are unknown. Here, we have analyzed the solution structure of ARMET. ARMET has an entirely α-helical structure, which is composed of two distinct domains. Positive charges are dispersed on the surfaces of both domains and across a linker structure. Trypsin digestion and 15N relaxation experiments indicate that the tumbling of the N-terminal and C-terminal domains is effectively independent. These results suggest that ARMET may hold a negatively charged molecule using the two positively charged domains

Ni@onion-like carbon and Co@amorphous carbon: control of carbon structures by metal ion species in MOFs

We first report the facile synthesis of metal-carbon composites consisting of metal nanoparticles (NPs) and different types of carbon species: onion-like and amorphous carbon, Ni@onion-like carbon and Co@amorphous carbon. By simply changing the metal species in an isostructural metal-organic framework, thermal decompositions of MOF-74 directly afforded different types of metal NPs and carbon composites, which exhibited good electrical conductivity. In particular, the Ni@onion-like carbon, having a well-ordered carbon structure, had high electrical conductivity (sigma = 5.3 omega(-1) cm(-1) at 295 K), explained by a modified model of the Efros-Shklovskii variable range hopping

Crystal Structure Control of Binary and Ternary Solid-Solution Alloy Nanoparticles with a Face-Centered Cubic or Hexagonal Close-Packed Phase

The crystal structure significantly affects the physical and chemical properties of solids. However, the crystal structure-dependent properties of alloys are rarely studied because controlling the crystal structure of an alloy at the same composition is extremely difficult. Here, for the first time, we successfully demonstrate the synthesis of binary Ru–Pt (Ru/Pt = 7:3) and Ru–Ir (Ru/Ir = 7:3) and ternary Ru–Ir–Pt (Ru/Ir/Pt = 7:1.5:1.5) solid-solution alloy nanoparticles (NPs) with well-controlled hexagonal close-packed (hcp) and face-centered cubic (fcc) phases, through the chemical reduction method. The crystal structure control is realized by precisely tunning the reduction speeds of the metal precursors. The effect of the crystal structure on the catalytic performance of solid-solution alloy NPs is systematically investigated. Impressively, all the hcp alloy NPs show superior electrocatalytic activities for the hydrogen evolution reaction in alkaline solution compared with the fcc alloy NPs. In particular, hcp-RuIrPt exhibits extremely high intrinsic (mass) activity, which is 3.1 (3.2) and 6.7 (6.9) times enhanced compared to that of fcc-RuIrPt and commercial Pt/C

Soft corrugated channel with synergistic exclusive discrimination gating for CO₂ recognition in gas mixture

二酸化炭素に対してのみゲートを開いて吸着する フレキシブル多孔性材料を開発. 京都大学プレスリリース. 2023-08-02.Interactive networks for capturing gas with high selectivity. 京都大学プレスリリース. 2023-08-02.Developing artificial porous systems with high molecular recognition performance is critical but very challenging to achieve selective uptake of a particular component from a mixture of many similar species, regardless of the size and affinity of these competing species. A porous platform that integrates multiple recognition mechanisms working cooperatively for highly efficient guest identification is desired. Here, we designed a flexible porous coordination polymer (PCP) and realised a corrugated channel system that cooperatively responds to only target gas molecules by taking advantage of its stereochemical shape, location of binding sites, and structural softness. The binding sites and structural deformation act synergistically, exhibiting exclusive discrimination gating (EDG) effect for selective gate-opening adsorption of CO₂ over nine similar gas molecules, including N₂, CH₄, CO, O₂, H₂, Ar, C₂H₆, and even higher-affinity gases such as C₂H₂ and C₂H4. Combining in-situ crystallographic experiments with theoretical studies, it is clear that this unparalleled ability to decipher the CO₂ molecule is achieved through the coordination of framework dynamics, guest diffusion, and interaction energetics. Furthermore, the gas co-adsorption and breakthrough separation performance render the obtained PCP an efficient adsorbent for CO₂ capture from various gas mixtures

Selective sorption of oxygen and nitrous oxide by an electron donor-incorporated flexible coordination network

Incorporating strong electron donor functionality into flexible coordination networks is intriguing for sorption applications due to a built-in mechanism for electron-withdrawing guests. Here we report a 2D flexible porous coordination network, [Ni₂(4, 4′-bipyridine)(VTTF)₂]n(1) (where H₂VTTF = 2, 2′-[1, 2-bis(4-benzoic acid)-1, 2ethanediylidene]bis-1, 3-benzodithiole), which exhibits large structural deformation from the as-synthesized or open phase (1α) into the closed phase (1β) after guest removal, as demonstrated by X-ray and electron diffraction. Interestingly, upon exposure to electron-withdrawing species, 1β reversibly undergoes guest accommodation transitions; 1α⊃O₂ (90 K) and 1α⊃N₂O (185 K). Moreover, the 1β phase showed exclusive O₂ sorption over other gases (N₂, Ar, and CO) at 120 K. The phase transformations between the 1α and 1β phases under these gases were carefully investigated by in-situ X-ray diffraction, in-situ spectroscopic studies, and DFT calculations, validating that the unusual sorption was attributed to the combination of flexible frameworks and VTTF (electron-donor) that induces strong interactions with electron-withdrawing species

A Novel CLEIA for FGF23

Introduction: Measurement of fibroblast growth factor 23 (FGF23) has been reported to be clinically useful for the differential diagnosis of chronic hypophosphatemia. However, assays for research use only are available in Japan. Thus, the objective of this study was to examine the clinical utility of a novel and automated chemiluminescent enzyme immunoassay for the measurement of FGF23. Materials and Methods: Participants were recruited from July 2015 to January 2017 at six facilities in Japan. Thirty-eight patients with X-linked hypophosphatemic rickets (XLH; 15 males, 23 females, age 0–66 years), five patients with tumour-induced osteomalacia (TIO; 3 males, 2 females, age 60–73 years), and twenty-two patients with hypophosphatemia (11 males, 11 females, age 1–75 years) caused due to other factors participated in this study. Results: With the clinical cut-off value of FGF23 at 30.0 pg/mL indicated in the Diagnostic Guideline of Rickets/Osteomalacia in Japan, the sensitivity and specificity of FGF23-related hypophosphatemic rickets/osteomalacia without vitamin D deficiency (disease group-1) were 100% and 81.8%, respectively, which distinguished it from non-FGF23-related hypophosphatemia (disease group-2). Furthermore, the diagnostic sensitivity of FGF23-related hypophosphatemia with vitamin D deficiency remained at 100%. Among the four patients with FGF23 levels ≥ 30.0 pg/mL in disease group-2, two patients with relatively higher FGF23 values were suspected to have genuine FGF23-related hypophosphatemia, due to the ectopic production of FGF23 in pulmonary and prostate small cell carcinomas. Conclusion: The novel FGF23 assay tested in this study is useful for the differential diagnosis of hypophosphatemic rickets/osteomalacia in a clinical setting

Motion of methanol adsorbed in porous coordination polymer with paramagnetic metal ions

Molecular motions of methanol adsorbed in 1D nano-channels of pillared-layer coordination polymer with paramagnetic metal ions have been studied by 2H NMR together with X-ray crystallography

The Nature of Ultra-Luminous Compact X-Ray Sources in Nearby Spiral Galaxies

Studies were made of ASCA spectra of seven ultra-luminous compact X-ray sources (ULXs) in nearby spiral galaxies; M33 X-8 (Takano et al. 1994), M81 X-6 (Fabbiano 1988b; Kohmura et al. 1994; Uno 1997), IC 342 Source 1 (Okada et al. 1998), Dwingeloo 1 X-1 (Reynolds et al. 1997), NGC 1313 Source B (Fabbiano & Trinchieri 1987; Petre et al. 1994), and two sources in NGC 4565 (Mizuno et al. 1999). With the 0.5--10 keV luminosities in the range 10^{39-40} ergs/s, they are thought to represent a class of enigmatic X-ray sources often found in spiral galaxies. For some of them, the ASCA data are newly processed, or the published spectra are reanalyzed. For others, the published results are quoted. The ASCA spectra of all these seven sources have been described successfully with so called multi-color disk blackbody (MCD) emission arising from optically-thick standard accretion disks around black holes. Except the case of M33 X-8, the spectra do not exhibit hard tails. For the source luminosities not to exceed the Eddington limits, the black holes are inferred to have rather high masses, up to ~100 solar masses. However, the observed innermost disk temperatures of these objects, Tin = 1.1--1.8 keV, are too high to be compatible with the required high black-hole masses, as long as the standard accretion disks around Schwarzschild black holes are assumed. Similarly high disk temperatures are also observed from two Galactic transients with superluminal motions, GRO 1655-40 and GRS 1915+105. The issue of unusually high disk temperature may be explained by the black hole rotation, which makes the disk get closer to the black hole, and hence hotter.Comment: submitted to ApJ, December 199

Duodenal mucosal hemodynamics in patients with liver cirrhosis.

Clinical studies show that patients with liver cirrhosis associated with portal hypertension have a high incidence of duodenal ulcer and duodenitis. However, little information is available concerning pathophysiological process of such duodenal diseases in liver cirrhosis. Hemodynamics of the duodenal mucosa was studied in cirrhotics with esophageal varices (68 cases) and in noncirrhotics with non-ulcer dyspepsia (37 cases) as well. In each group, hemoglobin concentration in the peripheral venous blood was measured, and mucosal hemodynamics was examined in 4 regions of the duodenum by endoscopic reflectance spectrophotometer. No significant intergroup difference was noted in the mean age or sex ratio. Hemoglobin concentration in the peripheral venous blood was significantly lower (p less than 0.01) in the cirrhotics. There were no significant intergroup differences in duodenal mucosal blood volume. However, the cirrhotics showed significantly lower oxygen saturation of hemoglobin in all regions of the duodenum (p less than 0.01). These results show that the cirrhotics with esophageal varices had relative increase in blood volume and decrease in oxygen saturation of hemoglobin in the duodenal mucosa. Such microcirculatory disturbances seem to predispose liver cirrhosis patients to duodenal injury.</p