Exchanged: The organic radical 2‐azaadamantan‐N‐oxyl (AZA; see picture) is found to be a stable and highly reactive redox mediator in dye‐sensitized solar cell (DSSC) electrolytes. This radical has ...an appropriate redox potential and significantly high values for the diffusivity, heterogeneous electron‐transfer rate, and electron self‐exchange reaction rate. In a DSSC the AZA‐based electrolyte achieves an excellent photovoltaic performance.
Autoionization and subsequent proton transfer processes determine the proton activity inherent to water molecular systems. In this study, we provide direct experimental evidence that the proton ...activity is markedly enhanced at the surface of crystalline ice, on the basis of the simultaneous observation of H/D exchange of water molecules at the surface and in the interior of well-defined double-layer ice films composed of H2O and D2O. Thermal desorption mass spectrometry showed clear signatures derived from the surface H/D exchange equilibrium, whereas infrared absorption spectroscopy indicated no appreciable H/D exchange progress in the interior. Detailed kinetic analyses revealed that the rate of H/D exchange at the surface is at least 3 orders of magnitude higher than in the interior. This drastic enhancement of the proton activity suggests an extremely high concentration of surface-hydrated protons in comparison with those in the bulk. Our results also highlight the impact of the local hydrogen-bond structure on the autoionization of water molecules.
The crystallization mechanism and kinetics of amorphous materials are of paramount importance not only in basic science but also in the application field because they are closely related to their ...thermal stability. In the case of amorphous nanomaterials, thermal stability distinctively different from that of bulk materials often emerges. Despite intensive studies in the past, a thorough understanding of the stability at the molecular level has not been reached particularly on how crystallization processes depend on size and are influenced by their surface and interface. In this article, we report the film-size-dependent crystallization of thermally relaxed nonporous ASW ultrathin films on a Pt(111) surface as a benchmark system of amorphous molecular films. The crystallization processes at the surface and interior of the ASW ultrathin films are monitored simultaneously with thermal desorption and infrared reflection absorption, respectively, as a function of the film thickness. Here, we demonstrate that the crystallization is initiated solely by "homogeneous nucleation" irrespective of the film thickness while the crystallization rate remarkably depends on the thickness; the rate of 5-layer (∼1.5 nm) ASW films is one order of magnitude higher than that of 20-layer (∼6 nm) films. Moreover, we found a clear correlation between the film-thickness-dependent crystallization kinetics and microscopic structural disorder associated with the broad distribution of hydrogen-bond lengths between water molecules.
Film-size-dependent homogeneous crystallization of nanoscopic amorphous ice is demonstrated with a clear correlation between the crystallization kinetics and microscopic structure.
Background:Several new treatments for chronic thromboembolic pulmonary hypertension (CTEPH) have appeared in recent years, which have led to changes in the treatment algorithm. Changes in survival ...rates and prognostic factors, however, have not been estimated so far.Methods and Results:Two hundred and eighty patients were diagnosed with CTEPH at Chiba University Hospital between June 1986 and June 2016. Survival rate was investigated by date of treatment initiation (group 1, 1986–1998; group 2, 1999–2008; group 3, 2009–2016). Survival rates were also evaluated by treatment strategy: balloon pulmonary angioplasty (BPA), pulmonary endarterectomy (PEA), and medical treatment. Group 3 had significantly better disease-specific survival than groups 1 and 2 (5-year survival: 91.9% vs. 67.1%, 77.0%, respectively). For the non-PEA (BPA+medication) strategy, group 3 had better disease-specific survival than groups 1 and 2 (5-year survival: 94.9% vs. 54.6%, 74.2%, respectively). The PEA strategy had significantly better survival than the medication strategy in groups 1 and 2, whereas no difference was observed between the BPA, PEA, and medication strategies in group 3.Conclusions:Survival in CTEPH in the recent era has significantly improved, especially in non-PEA patients. BPA and selective pulmonary vasodilators could improve survival in the non-PEA group. In the present study, no difference in survival was found between PEA and non-PEA.
•Investigation of MTAP IHC as a good alternative assay to 9p21 FISH for diagnostics.•MTAP IHC discriminates sarcomatoid mesothelioma from fibrous pleuritis.•A combination of MTAP IHC and BAP1 IHC ...increases the sensitivity for MPM diagnosis.
Histologic diagnosis of malignant pleural mesothelioma (MPM) is not always straightforward. Loss of BRCA1-associated protein 1 (BAP1) expression as detected by immunohistochemistry (IHC) (BAP1 IHC) and homozygous deletion (HD) of 9p21 as detected by fluorescencein situ hybridization (FISH) (9p21 FISH) are effective for distinguishing malignant mesothelial proliferation from benign proliferation. We have previously reported that immunohistochemical expression of the protein product of the methylthioadenosine phosphorylase (MTAP) gene, which is localized in the 9p21 chromosomal region, is correlated with the deletion status of 9p21 FISH in MPM tissues. In this study, we investigated whether a combination of MTAP and BAP1 IHC could distinguish sarcomatoid MPM from fibrous pleuritis.
We examined IHC expressions of MTAP and BAP1 and 9p21 FISH in sarcomatoid/desmoplastic (n = 18) and biphasic MPM (n = 12) and in fibrous pleuritis (n = 17). In biphasic MPM, only sarcomatoid components were evaluated for IHC and FISH. The sensitivity and specificity of each detection assay for discriminating MPM cases from fibrous pleuritis was determined. In addition, we compared the IHC expression of MTAP with the deletion status of 9p21 FISH.
MTAP IHC and BAP1 IHC showed 80% and 36.7% sensitivity, respectively, and both showed 100% specificity in differentiating MPM from fibrous pleuritis. A combination of MTAP and BAP1 IHC yielded greater sensitivity (90%) than that detected for MTAP IHC alone or BAP1 IHC alone. Moreover, a high degree of concordance was observed between the results of MTAP IHC and HD of 9p21 FISH (κ = 0.63).
With an accurate interpretation of results, combined MTAP and BAP1 IHC is a reliable and effective method for distinguishing sarcomatoid MPM from fibrous pleuritis.
Pulmonary arterial hypertension (PAH) is characterized by progressive obstructive remodeling of pulmonary arteries. However, no reports have described the causative role of the autophagic pathway in ...pulmonary vascular endothelial cell (EC) alterations associated with PAH. This study investigated the time-dependent role of the autophagic pathway in pulmonary vascular ECs and pulmonary vascular EC kinesis in a severe PAH rat model (Sugen/hypoxia rat) and evaluated whether timely induction of the autophagic pathway by rapamycin improves PAH. Hemodynamic and histological examinations as well as flow cytometry of pulmonary vascular EC-related autophagic pathways and pulmonary vascular EC kinetics in lung cell suspensions were performed. The time-dependent and therapeutic effects of rapamycin on the autophagic pathway were also assessed. Sugen/hypoxia rats treated with the vascular endothelial growth factor receptor blocker SU5416 showed increased right ventricular systolic pressure (RVSP) and numbers of obstructive vessels due to increased pulmonary vascular remodeling. The expression of the autophagic marker LC3 in ECs also changed in a time-dependent manner, in parallel with proliferation and apoptotic markers as assessed by flow cytometry. These results suggest the presence of cross talk between pulmonary vascular remodeling and the autophagic pathway, especially in small vascular lesions. Moreover, treatment of Sugen/hypoxia rats with rapamycin after SU5416 injection activated the autophagic pathway and improved the balance between cell proliferation and apoptosis in pulmonary vascular ECs to reduce RVSP and pulmonary vascular remodeling. These results suggested that the autophagic pathway can suppress PAH progression and that rapamycin-dependent activation of the autophagic pathway could ameliorate PAH.
Pulmonary endothelial damage has a negative impact on the maintenance of normal pulmonary vascular function. Such damage results in delayed thrombus dissolution and vascular remodeling in chronic ...thromboembolic pulmonary hypertension (CTEPH). Although endothelial progenitor cells (EPCs) may be incorporated into neovasculature during vascular repair, their function in CTEPH remains unclarified, especially under the augmentation of soluble guanylate cyclase (sGC) activity.
We evaluated the effect of EPCs on endothelial function and compared the effect of riociguat, a sGC stimulator, on the number and function of circulating EPCs in two groups of CTEPH patients. The two groups consisted 16 CTEPH patients who were treatment naïve (Naïve group), and 14 CTEPH patients who were being treated with riociguat, a sGC stimulator (Riociguat group). The number of circulating EPCs in the Riociguat group was significantly higher than that in the Naïve group. Gene expression levels associated with angiogenesis were significantly higher in EPCs of the Riociguat group. EPC-stimulated tube formation and migration of human pulmonary microvascular endothelial cell (hPMVEC) in the Riociguat group exceeded that in the Naïve group. The angiogenic ability of hPMVECs stimulated by EPCs in the Riociguat group was enhanced compared to that of the sGC stimulator, BAY 41–2272.
These findings indicate that riociguat may induce EPCs to play a protective role via modulation of endothelial functions associated with CTEPH.
Endothelial dysfunction exacerbates CTEPH. Riociguat enhanced the protective role of EPCs via neovascularization, which prevented vascular remodeling and alleviated CTEPH.
•The number of circulating EPCs increased in CTEPH patients treated with riociguat.•Riociguat increased tube formation and hPMVEC migration more than BAY 41–2272.•Findings suggest that EPCs of CTEPH patients taking riociguat play a protective role.
Electrochemical reversibility and fast bimolecular exchange reaction found for VO(salen) gave rise to a highly efficient redox mediation to enhance the photocurrent of a dye-sensitized solar cell, ...leading to an excellent photovoltaic performance with a conversion efficiency of 5.4%. A heterogeneous electron-transfer rate constant at an electrode (k0) and a second-order rate constant for an electron self-exchange reaction (k(ex)) were proposed as key parameters that dominate the charge transport property, which afforded a novel design concept for the mediators based on their kinetic aspects.
Pulmonary vascular endothelial function may be impaired by oxidative stress in endotoxemia-derived acute lung injury. Growing evidence suggests that endothelial-to-mesenchymal transition (EndMT) ...could play a pivotal role in various respiratory diseases; however, it remains unclear whether EndMT participates in the injury/repair process of septic acute lung injury. Here, we analyzed lipopolysaccharide (LPS)-treated mice whose total number of pulmonary vascular endothelial cells (PVECs) transiently decreased after production of reactive oxygen species (ROS), while the population of EndMT-PVECs significantly increased. NAD(P)H oxidase inhibition suppressed EndMT of PVECs. Most EndMT-PVECs derived from tissue-resident cells, not from bone marrow, as assessed by mice with chimeric bone marrow. Bromodeoxyuridine-incorporation assays revealed higher proliferation of capillary EndMT-PVECs. In addition, EndMT-PVECs strongly expressed c-kit and CD133. LPS loading to human lung microvascular endothelial cells (HMVEC-Ls) induced reversible EndMT, as evidenced by phenotypic recovery observed after removal of LPS. LPS-induced EndMT-HMVEC-Ls had increased vasculogenic ability, aldehyde dehydrogenase activity, and expression of drug resistance genes, which are also fundamental properties of progenitor cells. Taken together, our results demonstrate that LPS induces EndMT of tissue-resident PVECs during the early phase of acute lung injury, partly mediated by ROS, contributing to increased proliferation of PVECs.
Background:This study aimed to investigate the predictors of quality of life (QOL) in patients with chronic thromboembolic pulmonary hypertension (CTEPH), changes in QOL after surgical and medical ...treatments, and the relationship between baseline QOL and survival.Methods and Results:QOL was measured in 128 patients with CTEPH (male/female: 42/86, age: 56±12 years, surgical/medical: 65/63) using the Short-Form 36 (SF-36) questionnaire. Multiple regression analysis showed pulmonary vascular resistance (PVR) and 6-min walking distance (6MWD) were associated with physical functioning (PF) (P<0.01) and physical component summary (PCS) (P<0.01). In the surgical group, 7 subscales and 2 summary scores improved significantly, and in the medical group 6 subscales and the mental component summary, although the change in QOL was greater in the surgical group. The patients in the conventional therapy group with higher PF had significantly better survival than those with lower PF (5-years survival: 89.5% vs. 50.8%, P=0.002). This difference in survival was not observed in the group receiving pulmonary arterial hypertension (PAH)-specific therapy (100% vs. 100%, P=0.746).Conclusions:PVR and 6MWD were associated with PF or PCS in CTEPH patients. QOL improved after surgical or medical therapy, with a greater change in the surgical group. PAH-specific therapy improved survival in patients with lower PF at diagnosis. (Circ J 2015; 79: 2696–2702)
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