A new strategy to exploit maximum rate performance for aqueous batteries through a judicious selection of MOF-type electrodes.

A metal-organic framework (MOF) having a redox active 1,4,5,8-naphthalenetetracarboxdiimide (NDI) derivative in its organic linker shows excellent rate performance as an electrode material for aqueous batteries thanks to its large pores. Among aqueous electrolytes examined, K+-based ones exhibit the highest rate performance, which is caused by the highest mobility of the smallest hydrated K+ ion not only in the aqueous electrolyte but also in the electrode. Since the use of a counter electrode with insufficiently small pores for the full-cell configuration offsets this merit, our study may lead to a conclusion that the maximum rate performance for aqueous batteries will be accomplished only through further elaboration of both electrode materials with sufficiently large pores, in which hydrated ions can travel equally fast as those in the electrolyte.

Supported Noble Metal Catalysts and Adsorbents with Soft Lewis Acid Functions.

Heterogeneous noble metal catalysts exhibit various functions. Although their redox functions have been extensively studied, we focused on their soft Lewis acid functions. Supported Au, Pt, and Pd catalysts electrophilically attack the π-electrons of soft bases such as alkynes, alkenes, and aromatic compounds to perform addition and substitution reactions. Hydroamination, intramolecular cyclization of alkynyl carboxylic acids, isomerization of allylic esters, vinyl exchange reactions, Wacker oxidation, and oxidative homocoupling of aromatics are introduced based on a discussion of the active species and reaction mechanisms. Furthermore, the adsorption of sulfur compounds, which are soft bases, onto the supported AuNPs is discussed. The adsorption and removal of 1,3-dimethyltrisulfane (DMTS), which is the compound responsible for the stale odor of "hine-ka" in alcoholic beverages, particularly Japanese sake, is described.

Theoretical Mechanistic Investigation of the Dynamic Kinetic Resolution of N-Protected Amino Acid Esters using Phase-Transfer Catalysts.

A detailed theoretical mechanistic investigation on the dynamic kinetic resolution of N-protected amino acid esters using phase-transfer catalysts is described. Semiautomatic exhaustive conformation search of transition state (TS)-like structures were carried out using the ConFinder program and the pseudo-TS conformational search (PTSCS) method. This conformational search method successfully provided reasonable TS structures for determining the stereoselectivity in the asymmetric base hydrolysis of hexafluoroisopropyl (HFIP) esters as well as the racemization mechanism. Furthermore, the independent gradient model (IGM) analysis of the TS structures suggested that the H-bonding interactions with the oxyanion hole and π-stacking interactions are the common important features of the proposed TS structures that determine the stereoselectivity.

Validation of laser doppler flowmetry to measure dermal blood flow of the pinnae in dogs with pinnal alopecia.

BACKGROUND: Laser Doppler flowmetry (LDF) is a noninvasive method of measuring regional blood flow in humans. However, this method has not been widely applied to measure blood flow in dogs. HYPOTHESIS/OBJECTIVES: We hypothesised that LDF can measure changes in blood flow in canine pinnae accurately. The objectives were to determine whether LDF could accurately detect dermal blood flow changes in canine pinnae caused by haemodynamic drugs and characterize the dermal blood flow in dogs with pinnal alopecia. ANIMALS: Sixteen laboratory-owned healthy dogs, 25 client-owned healthy control dogs and six dogs with pinnal alopecia suspected to be secondary to ischaemic dermatoses. MATERIALS AND METHODS: Clinical doses of the haemodynamic drugs atropine, medetomidine and dibutyryl cyclic adenosine monophosphate (dBcAMP), as well as topical dBcAMP, were administered to healthy beagles. Subsequently, an LDF apparatus was attached to the pinnae to analyse changes in dermal blood flow. Finally, LDF was used to measure auricular dermal blood flow in dogs with pinnal alopecia compared to healthy dogs. RESULTS: Dermal blood flow increased after atropine injection, during dBcAMP infusion and after topical dBcAMP ointment application, and decreased after medetomidine injection. Auricular dermal blood flow (in mL/min/100 g tissue) was significantly (p < 0.05) lower in dogs with pinnal alopecia than in healthy dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Laser Doppler flowmetry is useful for measuring dermal blood flow in canine pinnae; it can be a noninvasive method to monitor ischaemic conditions of dog skin.

Effects of the Pt Shell Thickness on the Oxygen Reduction Reaction on a Well-Defined Pd@Pt Core-Shell Model Surface.

The effect of the Pt shell thickness on the oxygen reduction reaction (ORR) of a Pd@Pt core-shell catalyst was studied using surface science technics and computational approaches. We found Pt shells on Pd rods to be negatively charged because of charge transfer from the Pd substrate when the shell thicknesses were 0.5 or 1 monolayer (ML). The activities of the ORR of the model surface with a Pt shell of 0.5 or 1 ML were similar and more than twice the activities of a Pt/C or Pt rod. The relationship between the ORR activity and the thickness of the Pt shell was the exact opposite of the relationship between the Pt binding energy and the Pt shell thickness. The indication was that more negatively charged Pt had higher ORR activity. Density functional theory calculations confirmed that a single layer of Pt atoms located on Pd was negatively charged compared to pure Pt and resulted in a lower barrier to the rate-limiting step of the ORR.

Anchored Palladium Complex-Generated Clusters on Zirconia: Efficiency in Reductive N-Alkylation of Amines with Carbonyl Compounds under Hydrogen Atmosphere.

Carbon-nitrogen bond formation is an important method on both laboratory and industrial scales because it realizes the production of valuable pharmaceuticals, agrochemicals, and fine chemicals. Direct reductive N-alkylation of amines with carbonyl compounds via intermediary imine compounds, especially under catalytic hydrogenation conditions, is one of the most convenient, economical, and environmentally friendly methods for this process. Here we report a novel palladium species on zirconia having specific activity towards hydrogenation of imines but other carbonyl groups remaining intact. The present catalytic property offers a practical synthetic method of functionalized secondary amines by reductive N-alkylation under mild conditions with high atom-efficiency. Mechanistic studies revealed that the catalytically active species is the palladium cluster, which is generated in situ from molecular palladium complexes on the support by exposure to atmospheric hydrogen. These fundamental findings are expected to progress in developing novel cluster catalysts for chemical processes directed towards a sustainable society.

Rapid Destructive Arthropathy of the Knee in Parkinson's Disease with Pisa Syndrome: A Case of Knee-Spine Syndrome.

The changes occurring in knee osteoarthritis often cause alterations in the spinal loading condition, which further lead to degenerative changes. This close relationship of the knee and spine has been reported as knee-spine syndrome. A 60-year-old woman with Parkinson's disease (PD; Hoehn-Yahr stage IV) had severe knee pain with moderate lateral osteoarthritis of the knee (Kellgren-Lawrence classification grade II). Conservative therapy had no effect at all, and the knee developed destructive osteoarthritis rapidly without any traumatic episodes. The radiographic findings progressed to Kellgren-Lawrence grade IV within a month. Magnetic resonance imaging revealed partial depression of the joint surface, including shredded ossicles and substantial amounts of synovial fluid. The imaging findings were considered to be caused by a subchondral insufficiency fracture (SIF). Total knee arthroplasty was performed using a semiconstrained prosthesis. The alignment of her lower extremity improved, and the patient could walk without knee pain. The patient had Pisa syndrome, a lateral flexion of the trunk, which is a postural deformity of the trunk secondary to long-standing PD. The postural deformity in PD is not based on spinal deformity itself but on the loss of postural reflexes and the imbalance of muscle tonus. Her left knee pain appeared 1 month after L1-L4 posterior lumbar interbody fusion (PLIF) as the Pisa syndrome to her left side worsened. The more the trunk tilts to the lateral side, the center of the gravity axis will shift and pass through more lateral points of the knee and result in higher knee load. The stress concentration from the spine to the lateral joint of the knee caused lateral knee osteoarthritis, namely, knee-spine syndrome. When patients undergo correction surgery for adult spinal disorder with impairment of postural reflexes, they need to be followed up carefully regarding not only the spinal alignment but also the lower extremities.

Ubiquitin specific peptidase 32 acts as an oncogene in epithelial ovarian cancer by deubiquitylating farnesyl-diphosphate farnesyltransferase 1.

Epithelial ovarian cancer (EOC) is the seventh most common cancer worldwide and the deadliest gynecological malignancy because of its aggressiveness and high recurrence rate. To discover new therapeutic targets for EOC, we combined public EOC microarray datasets with our previous in vivo shRNA screening dataset. The top-ranked gene ubiquitin specific peptidase 32 (USP32), coding a deubiquitinating enzyme, is a component of the ubiquitin proteasome system. Clinically, USP32 is expressed in primary ovarian cancer, especially in metastatic peritoneal tumors, and negatively impacts the survival outcome. USP32 regulates proliferative and epithelial mesenchymal transition capacities that are associated with EOC progression. Proteomic analysis identified farnesyl-diphosphate farnesyltransferase 1 (FDFT1) as a novel substrate of USP32 that is an enzyme in the mevalonate pathway, essentially associated with cell proliferation and stemness. USP32 and FDFT1 expression was higher in tumor spheres than in adherent cells. Inhibition of USP32, FDFT1, or mevalonate pathway considerably suppressed tumor sphere formation, which was restored by adding squalene, a downstream product of FDFT1. These findings suggested that USP32-FDFT1 axis contributes to EOC progression, and could be novel therapeutic targets for EOC treatment.

Novel anti-flavivirus drugs targeting the nucleolar distribution of core protein.

The risk of infectious diseases caused by Flavivirus is increasing globally. Here, we developed a novel high-throughput screening (HTS) system to evaluate the inhibitory effects of compounds targeting the nuclear localization of the flavivirus core protein. We screened 4000 compounds based on their ability to inhibit the nuclear localization of the core protein, and identified over 20 compounds including inhibitors for cyclin dependent kinase and glycogen synthase kinase. The efficacy of the identified compounds to suppress viral growth was validated in a cell-based infection system. Remarkably, the nucleolus morphology was affected by the treatment with the compounds, suggesting that the nucleolus function is critical for viral propagation. The present HTS system provides a useful strategy for the identification of antivirals against flavivirus by targeting the nucleolar localization of the core protein.

Surface Modification of a Supported Pt Catalyst Using Ionic Liquids for Selective Hydrodeoxygenation of Phenols into Arenes under Mild Conditions.

The selective and efficient removal of oxygenated groups from lignin-derived phenols is a critical challenge to utilize lignin as a source for renewable aromatic chemicals. This report describes how surface modification of a zeolite-supported Pt catalyst using ionic liquids (ILs) remarkably increases selectivity for the hydrodeoxygenation (HDO) of phenols into arenes under mild reaction conditions using atmospheric pressure H2 . Unmodified Pt/H-ZSM-5 converts phenols into aliphatic species as the major products along with a slight amount of arenes (10 % selectivity). In contrast, the catalyst modified with an IL, 1-butyl-3-methylimidazolium triflate, keeps up to 76 % selectivity for arenes even at a nearly complete conversion of phenols. The IL on the surface of Pt catalyst may offer the adsorption of phenols in an edge-to-face manner onto the surface, thus accelerating the HDO without the ring hydrogenation.

Enantioselective Protonation of Enol Esters with Bifunctional Phosphonium/Thiourea Catalysts.

Bifunctional phosphonium/thioureas derived from tert-leucine behaved as highly selective catalysts for enantioselective protonation of enol esters, providing α-chiral ketones in yields of up to 99% with high enantioselectivities (up to 98.5:1.5 er). Control experiments clarified that a bulky tert-butyl group and phosphonium and thiourea moieties were necessary to achieve such high stereoselectivity. In addition, mechanistic investigations indicated the catalyst was converted to the corresponding betaine species, which served as a monomolecular catalyst.

USP15 Participates in Hepatitis C Virus Propagation through Regulation of Viral RNA Translation and Lipid Droplet Formation.

Hepatitis C virus (HCV) utilizes cellular factors for efficient propagation. Ubiquitin is covalently conjugated to the substrate to alter its stability or to modulate signal transduction. In this study, we examined the importance of ubiquitination for HCV propagation. We found that inhibition of deubiquitinating enzymes (DUBs) or overexpression of nonspecific DUBs impaired HCV replication, suggesting that ubiquitination regulates HCV replication. To identify specific DUBs involved in HCV propagation, we set up RNA interference (RNAi) screening against DUBs and successfully identified ubiquitin-specific protease 15 (USP15) as a novel host factor for HCV propagation. Our studies showed that USP15 is involved in translation of HCV RNA and production of infectious HCV particles. In addition, deficiency of USP15 in human hepatic cell lines (Huh7 and Hep3B/miR-122 cells) but not in a nonhepatic cell line (293T cells) impaired HCV propagation, suggesting that USP15 participates in HCV propagation through the regulation of hepatocyte-specific functions. Moreover, we showed that loss of USP15 had no effect on innate immune responses in vitro and in vivo We also found that USP15-deficient Huh7 cells showed reductions in the amounts of lipid droplets (LDs), and the addition of palmitic acids restored the production of infectious HCV particles. Taken together, these data suggest that USP15 participates in HCV propagation by regulating the translation of HCV RNA and the formation of LDs.IMPORTANCE Although ubiquitination has been shown to play important roles in the HCV life cycle, the roles of deubiquitinating enzymes (DUBs), which cleave ubiquitin chains from their substrates, in HCV propagation have not been investigated. Here, we identified USP15 as a DUB regulating HCV propagation. USP15 showed no interaction with viral proteins and no participation in innate immune responses. Deficiency of USP15 in Huh7 cells resulted in suppression of the translation of HCV RNA and reduction in the amounts of lipid droplets, and the addition of fatty acids partially restored the production of infectious HCV particles. These data suggest that USP15 participates in HCV propagation in hepatic cells through the regulation of viral RNA translation and lipid metabolism.

Selective adsorption of 1,3-dimethyltrisulfane (DMTS) responsible for aged odour in Japanese sake using supported gold nanoparticles.

Gold (Au) nanoparticles (NPs) supported on SiO2 (Au/SiO2) were prepared by a practical impregnation method and applied as an adsorbent for 1,3-dimethyltrisulfane (DMTS), which is responsible for an unpleasant odour in drinks, especially Japanese sake. Compared with a conventional adsorbent, activated carbon, Au/SiO2 selectively reduced the DMTS concentration in Japanese sake without decreasing the concentrations of other aromatic components. DFT calculations revealed that the selective adsorption of DMTS occurred through the formation of a stable intermediate. The size of the supported Au NPs was controlled by the preparation conditions and determined from TEM observations and XRD measurements, and the size was ranged from 2.4 nm to 30 nm. Au/SiO2 having Au NPs with a diameter of 2.4 nm adsorbed DMTS the most efficiently. Smaller Au NPs showed better DMTS adsorption capabilities because larger amounts of Au atoms were exposed on their surfaces in the size range of this study. Langmuir-type monolayer adsorption and one-to-one binding of Au-S are proposed to occur based on an adsorption isotherm experiment. Even though significant differences of the fruity aroma score were not observed in the sensory evaluation between Au/SiO2 and activated carbon for this less aromatic Japanese sake, Au/SiO2 selectively decreased the DMTS concentration in the instrumental analysis.

Infection with flaviviruses requires BCLXL for cell survival.

BCL2 family proteins including pro-survival proteins, BH3-only proteins and BAX/BAK proteins control mitochondria-mediated apoptosis to maintain cell homeostasis via the removal of damaged cells and pathogen-infected cells. In this study, we examined the roles of BCL2 proteins in the induction of apoptosis in cells upon infection with flaviviruses, such as Japanese encephalitis virus, Dengue virus and Zika virus. We showed that survival of the infected cells depends on BCLXL, a pro-survival BCL2 protein due to suppression of the expression of another pro-survival protein, MCL1. Treatment with BCLXL inhibitors, as well as deficient BCLXL gene expression, induced BAX/BAK-dependent apoptosis upon infection with flaviviruses. Flavivirus infection attenuates cellular protein synthesis, which confers reduction of short-half-life proteins like MCL1. Inhibition of BCLXL increased phagocytosis of virus-infected cells by macrophages, thereby suppressing viral dissemination and chemokine production. Furthermore, we examined the roles of BCLXL in the death of JEV-infected cells during in vivo infection. Haploinsufficiency of the BCLXL gene, as well as administration of BH3 mimetic compounds, increased survival rate after challenge of JEV infection and suppressed inflammation. These results suggest that BCLXL plays a crucial role in the survival of cells infected with flaviviruses, and that BCLXL may provide a novel antiviral target to suppress propagation of the family of Flaviviridae viruses.

Synchrony of the first division as an index of the blastocyst formation rate during embryonic development.

Purpose: To devise an uninvasive selection system for human embryos with high developmental potential after a single oocyte retrieval cycle by comparing the in vitro and in vivo effectiveness of first division synchrony against subsequent embryonic developmental stages. Methods: The effects of using assisted reproductive technology on 948 embryos that were produced in 137 cycles were examined by dividing the embryos into "early cleavage" (first division within 25.90 hours) and "late cleavage" (first division at or after 25.90 hours) groups and comparing the blastocysts and good-quality blastocyst formation rates between the two groups. These two groups were each divided further into "high synchrony" (first division synchrony within 3.96 hours) and "low synchrony" (first division synchrony at or after 3.96 hours) groups. The blastocysts, good-quality blastocyst formation rates, and pregnancy rates were compared among these four groups. Results: Both the blastocysts and good-quality blastocyst formation rates were significantly higher in the early-cleavage groups than in the late-cleavage groups. The blastocyst formation rate of the latter was also significantly increased in the high-synchrony, compared with the low-synchrony, group. Conclusion: First division synchrony in a single oocyte retrieval cycle could be a useful assessment of the blastocyst formation rate that enables the selection of viable embryos at an early stage of culture.

Backscattered electron imaging and elemental analysis of rapidly frozen plant cells using variable accelerating voltage.

Rapidly frozen rosemary leaves were observed at variable accelerating voltages in a low-vacuum scanning electron microscope equipped with a cryo transfer system. After water was sublimated from the fractured face of the leaf, distinct backscattered electron (BSE) images were obtained depending on the accelerating voltages applied. At 5 kV, surface cell wall structure was observed, whereas at 10 and 15 kV chloroplasts lining the inside of the cell wall and membrane were visualized. With energy dispersive X-ray microanalysis, elemental information corresponding to the BSE images was obtained. Besides visualization of the structures and elemental composition close to the living state, information on layers at different depths from the surface could be detected by varying the accelerating voltage in this system.

Characterization of SPP inhibitors suppressing propagation of HCV and protozoa.

Signal peptide peptidase (SPP) is an intramembrane aspartic protease involved in the maturation of the core protein of hepatitis C virus (HCV). The processing of HCV core protein by SPP has been reported to be critical for the propagation and pathogenesis of HCV. Here we examined the inhibitory activity of inhibitors for γ-secretase, another intramembrane cleaving protease, against SPP, and our findings revealed that the dibenzoazepine-type structure in the γ-secretase inhibitors is critical for the inhibition of SPP. The spatial distribution showed that the γ-secretase inhibitor compound YO-01027 with the dibenzoazepine structure exhibits potent inhibiting activity against SPP in vitro and in vivo through the interaction of Val223 in SPP. Treatment with this SPP inhibitor suppressed the maturation of core proteins of all HCV genotypes without the emergence of drug-resistant viruses, in contrast to the treatment with direct-acting antivirals. YO-01027 also efficiently inhibited the propagation of protozoa such as Plasmodium falciparum and Toxoplasma gondii These data suggest that SPP is an ideal target for the development of therapeutics not only against chronic hepatitis C but also against protozoiasis.

Regulation of Apoptosis during Flavivirus Infection.

Apoptosis is a type of programmed cell death that regulates cellular homeostasis by removing damaged or unnecessary cells. Its importance in host defenses is highlighted by the observation that many viruses evade, obstruct, or subvert apoptosis, thereby blunting the host immune response. Infection with Flaviviruses such as Japanese encephalitis virus (JEV), Dengue virus (DENV) and West Nile virus (WNV) has been shown to activate several signaling pathways such as endoplasmic reticulum (ER)-stress and AKT/PI3K pathway, resulting in activation or suppression of apoptosis in virus-infected cells. On the other hands, expression of some viral proteins induces or protects apoptosis. There is a discrepancy between induction and suppression of apoptosis during flavivirus infection because the experimental situation may be different, and strong links between apoptosis and other types of cell death such as necrosis may make it more difficult. In this paper, we review the effects of apoptosis on viral propagation and pathogenesis during infection with flaviviruses.

Wacker Oxidation of Terminal Alkenes Over ZrO2 -Supported Pd Nanoparticles Under Acid- and Cocatalyst-Free Conditions.

Highly efficient Wacker oxidation of aromatic or aliphatic terminal alkenes into methyl ketones and benzofurans is developed by using reusable Pd0 nanoparticles (NPs) supported on ZrO2 under acid- and cocatalyst-free conditions. Molecular oxygen or air can be utilized as the terminal oxidant, which results in the formation of H2 O as the only theoretical byproduct. The activation of the Pd NPs by O2 plays an important role in promoting this reaction. Interestingly, PdO supported on ZrO2 showed no activity. Additionally, the Pd particle size significantly affects the catalytic activity, with an apparent optimal diameter of 4-12 nm. In addition to the heterogeneous catalyst forms, the Pd NPs can be generated from a Pd0 complex during the reaction, and these particles are even recyclable.

A Method of Calculating Functional Independence Measure at Discharge from Functional Independence Measure Effectiveness Predicted by Multiple Regression Analysis Has a High Degree of Predictive Accuracy.

BACKGROUND: Multiple linear regression analysis is often used to predict the outcome of stroke rehabilitation. However, the predictive accuracy may not be satisfactory. The objective of this study was to elucidate the predictive accuracy of a method of calculating motor Functional Independence Measure (mFIM) at discharge from mFIM effectiveness predicted by multiple regression analysis. METHODS: The subjects were 505 patients with stroke who were hospitalized in a convalescent rehabilitation hospital. The formula "mFIM at discharge = mFIM effectiveness × (91 points - mFIM at admission) + mFIM at admission" was used. By including the predicted mFIM effectiveness obtained through multiple regression analysis in this formula, we obtained the predicted mFIM at discharge (A). We also used multiple regression analysis to directly predict mFIM at discharge (B). The correlation between the predicted and the measured values of mFIM at discharge was compared between A and B. RESULT: The correlation coefficients were .916 for A and .878 for B. CONCLUSION: Calculating mFIM at discharge from mFIM effectiveness predicted by multiple regression analysis had a higher degree of predictive accuracy of mFIM at discharge than that directly predicted.