Selective hydrogenation of acetophenone with supported Pd and Rh catalysts in water, organic solvents, and CO2-dissolved expanded liquids

Solvent effects were investigated for selective hydrogenation of acetophenone (AP) with commercial 5% Pd/Al2O3 and 5% Pd/C catalysts using polar and nonpolar solvents. The rate of AP hydrogenation varied with the solvents used in different ways depending on the catalysts used. The highest AP conversion was achieved with water for the two catalysts and the AP conversion was correlated with hydrogen-bond-acceptance (HBA) capability (beta) for Pd/Al2O3 and hydrogen-bond-donation (HBD) capability (alpha) for Pd/C. These trends were the same as the corresponding solvent effects obtained previously with Rh/ Al2O3 and Rh/C catalysts, respectively (Green Chem., 2015, 17, 1877-1883). The influence of solvents on the rate of AP hydrogenation depends on the support materials and not on the metal species. Furthermore, AP hydrogenation was conducted with the four supported noble metal catalysts in different solvents pressurized by CO2 (CO2-dissolved expanded solvents). The influence of CO2 pressurization on the rate of reaction, the product selectivity, and the catalyst life was investigated to know whether or not CO2 molecules could function as a reaction promoter in heterogeneous AP hydrogenation reactions with supported Pd and Rh catalysts in different solvents

Establishment of anti-DKK3 peptide for the cancer control in head and neck squamous cell carcinoma (HNSCC)

Background: Head and neck squamous cell carcinoma (HNSCC) is the most common malignant tumor of the head and neck. We identified cancer‑specific genes in HNSCC and focused on DKK3 expression. DKK3 gene codes two iso‑forms of proteins (secreted and non‑secreted) with two distinct cysteine rich domains (CRDs). It is reported that DKK3 functions as a negative regulator of oncogenic Wnt signaling and, is therefore, considered to be a tumor suppressor gene. However, our series of studies have demonstrated that DKK3 expression is specifically high in HNSCC tissues and cells, and that DKK3 might determine the malignant potentials of HNSCC cells via the activation of Akt. Further analyses strongly suggested that both secreted DKK3 and non‑secreted DKK3 could activate Akt signaling in discrete ways, and consequently exert tumor promoting effects. We hypothesized that DKK3 might be a specific druggable target, and it is necessary to establish a DKK3 inhibitor that can inhibit both secreted and non‑secreted isoforms of DKK3.Methods: Using inverse polymerase chain reaction, we generated mutant expression plasmids that express DKK3 without CRD1, CRD2, or both CRD1 and CRD2 (DKK3ΔC1, DKK3ΔC2, and DKK3ΔC1ΔC2, respectively). These plasmids were then transfected into HNSCC‑derived cells to determine the domain responsible for DKK3‑mediated Akt activation. We designed antisense peptides using the MIMETEC program, targeting DKK3‑specific amino acid sequences within CRD1 and CRD2. The structural models for peptides and DKK3 were generated using Raptor X, and then a docking simulation was performed using CluPro2. Afterward, the best set of the peptides was applied into HNSCC‑derived cells, and the effects on Akt phosphorylation, cellular proliferation, invasion, and migration were assessed. We also investigated the therapeutic effects of the peptides in the xenograft models.Results: Transfection of mutant expression plasmids and subsequent functional analyses revealed that it is necessary to delete both CRD1 and CRD2 to inhibit Akt activation and inhibition of proliferation, migration, and invasion. The inhibitory peptides for CRD1 and CRD2 of DKK3 significantly reduced the phosphorylation of Akt, and consequently suppressed cellular proliferation, migration, invasion and in vivo tumor growth at very low doses.Conclusions: This inhibitory peptide represents a promising new therapeutic strategy for HNSCC treatment

Efficacy and safety of micafungin in empiric and D-index-guided early antifungal therapy for febrile neutropenia ; A subgroup analysis of the CEDMIC trial

Objectives: The D-index is defined as the area over the neutrophil curve during neutropenia. The CEDMIC trial confirmed the noninferiority of D-index-guided early antifungal therapy (DET) using micafungin to empirical antifungal therapy (EAT). In this study, we evaluated the efficacy and safety of micafungin in these settings. Methods: From the CEDMIC trial, we extracted 67 and 113 patients who received micafungin in the DET and EAT groups, respectively. Treatment success was defined as the fulfilment of all components of a five-part composite end point. Fever resolution was evaluated at seven days after the completion of therapy. Results: The proportion of high-risk treatments including induction chemotherapy for acute leukemia and allogeneic hematopoietic stem cell transplantation was significantly higher in the DET group than in the EAT group (82.1% vs. 52.2%). The efficacy of micafungin was 68.7% (95%CI: 56.2–79.4) and 79.6% (71.0–86.6) in the DET and EAT groups, respectively. When we focused on high-risk treatments, the efficacy was 69.1% (55.2–80.9%) and 78.0% (65.3–87.7%), respectively (P = 0.30). There was no significant difference in any of the 5 components between the two groups. Conclusions: The efficacy of micafungin in patients undergoing high-risk treatment was not strongly impaired in DET compared to that in EAT

Down-regulation of GATA1-dependent erythrocyte-related genes in the spleens of mice exposed to a space travel

Secondary lymphoid organs are critical for regulating acquired immune responses. The aim of this study was to characterize the impact of spaceflight on secondary lymphoid organs at the molecular level. We analysed the spleens and lymph nodes from mice flown aboard the International Space Station (ISS) in orbit for 35 days, as part of a Japan Aerospace Exploration Agency mission. During flight, half of the mice were exposed to 1 g by centrifuging in the ISS, to provide information regarding the effect of microgravity and 1 g exposure during spaceflight. Whole-transcript cDNA sequencing (RNA-Seq) analysis of the spleen suggested that erythrocyte-related genes regulated by the transcription factor GATA1 were significantly down-regulated in ISS-flown vs. ground control mice. GATA1 and Tal1 (regulators of erythropoiesis) mRNA expression was consistently reduced by approximately half. These reductions were not completely alleviated by 1 g exposure in the ISS, suggesting that the combined effect of space environments aside from microgravity could down-regulate gene expression in the spleen. Additionally, plasma immunoglobulin concentrations were slightly altered in ISS-flown mice. Overall, our data suggest that spaceflight might disturb the homeostatic gene expression of the spleen through a combination of microgravity and other environmental changes

The Japanese space gravitational wave antenna; DECIGO

DECi-hertz Interferometer Gravitational wave Observatory (DECIGO) is the future Japanese space gravitational wave antenna. DECIGO is expected to open a new window of observation for gravitational wave astronomy especially between 0.1 Hz and 10 Hz, revealing various mysteries of the universe such as dark energy, formation mechanism of supermassive black holes, and inflation of the universe. The pre-conceptual design of DECIGO consists of three drag-free spacecraft, whose relative displacements are measured by a differential Fabry– Perot Michelson interferometer. We plan to launch two missions, DECIGO pathfinder and pre- DECIGO first and finally DECIGO in 2024

DECIGO pathfinder

DECIGO pathfinder (DPF) is a milestone satellite mission for DECIGO (DECi-hertz Interferometer Gravitational wave Observatory) which is a future space gravitational wave antenna. DECIGO is expected to provide us fruitful insights into the universe, in particular about dark energy, a formation mechanism of supermassive black holes, and the inflation of the universe. Since DECIGO will be an extremely large mission which will formed by three drag-free spacecraft with 1000m separation, it is significant to gain the technical feasibility of DECIGO before its planned launch in 2024. Thus, we are planning to launch two milestone missions: DPF and pre-DECIGO. The conceptual design and current status of the first milestone mission, DPF, are reviewed in this article