Evaluation of Plant Ceramide Species-Induced Exosome Release from Neuronal Cells and Exosome Loading Using Deuterium Chemistry.

The extracellular accumulation of aggregated amyloid-ß (Aß) in the brain leads to the early pathology of Alzheimer's disease (AD). The administration of exogenous plant-type ceramides into AD model mice can promote the release of neuronal exosomes, a subtype of extracellular vesicles, that can mediate Aß clearance. In vitro studies showed that the length of fatty acids in mammalian-type ceramides is crucial for promoting neuronal exosome release. Therefore, investigating the structures of plant ceramides is important for evaluating the potential in releasing exosomes to remove Aß. In this study, we assessed plant ceramide species with D-erythro-(4E,8Z)-sphingadienine and D-erythro-(8Z)-phytosphingenine as sphingoid bases that differ from mammalian-type species. Some plant ceramides were more effective than mammalian ceramides at stimulating exosome release. In addition, using deuterium chemistry-based lipidomics, most exogenous plant ceramides were confirmed to be derived from exosomes. These results suggest that the ceramide-dependent upregulation of exosome release may promote the release of exogenous ceramides from cells, and plant ceramides with long-chain fatty acids can effectively release neuronal exosomes and prevent AD pathology.

CO2 methanation mechanism over Ni/Y2O3: an in situ diffuse reflectance infrared Fourier transform spectroscopic study.

Supported Ni catalysts are active in CO2 methanation. It is important to understand the reaction mechanism for the development of highly-active catalysts. In this study, we investigated the reaction pathways of CO2 methanation over Ni/Y2O3 and Ni/Al2O3 based on the adsorbates observed by diffuse reflectance infrared Fourier transform spectroscopy. For Ni/Al2O3, linear and bridged CO adsorbates were converted to nickel carbonyl hydride and/or formyl species, which would be further hydrogenated to methane. In contrast, the formation of formate adsorbates was specifically confirmed over Ni/Y2O3 under the CO2 methanation condition. The hydrogen molecule was activated by dissociatively-adsorbing on Ni particles. Then, the hydrogenation of formate adsorbates by the activated hydrogen species proceeded sequentially to form methane. The observed bridged CO species would not be a major intermediate for Ni/Y2O3.

S-allyl Cysteine Enhances Testosterone Production in Mice and Mouse Testis-Derived I-10 Cells.

Hypogonadism, associated with low levels of testosterone synthesis, has been implicated in several diseases. Recently, the quest for natural alternatives to prevent and treat hypogonadism has gained increasing research interest. To this end, the present study explored the effect of S-allyl cysteine (SAC), a characteristic organosulfur compound in aged-garlic extract, on testosterone production. SAC was administered at 50 mg/kg body weight intraperitoneally into 7-week-old BALB/c male mice in a single-dose experiment. Plasma levels of testosterone and luteinizing hormone (LH) and testis levels of proteins involved in steroidogenesis were measured by enzymatic immunoassay and Western blot, respectively. In addition, mouse testis-derived I-10 cells were also used to investigate the effect of SAC on steroidogenesis. In the animal experiment, SAC significantly elevated testosterone levels in both the plasma and the testis without changing the LH level in plasma and increased phosphorylated protein kinase A (p-PKA) levels. Similar results were also observed in I-10 cells. The findings demonstrating the increasing effect of SAC on p-PKA and mRNA levels of Cyp11a suggest that SAC increases the testosterone level by activating the PKA pathway and could be a potential target for hypogonadism therapeutics.

Electrochemical oxidation of 2-propanol over platinum and palladium electrodes in alkaline media studied by in situ attenuated total reflection infrared spectroscopy.

The electrochemical oxidation of 2-propanol over Pt and Pd electrodes was evaluated in alkaline media. Linear sweep voltammograms (LSVs), chronoamperograms (CAs), and simultaneous time-resolved attenuated total reflection infrared (ATR-IR) spectra of both electrodes were obtained in a 0.25 M KOH solution containing 1 M 2-propanol. The onset potential of 2-propanol oxidation for Pt was lower than that for Pd in LSVs while the degree of performance degradation observed for Pd was significantly smaller than that observed for Pt in CAs. The main product of 2-propanol oxidation was acetone over both electrodes and, over Pt only, acetone produced was catalytically oxidized to the enolate ion, which was accumulated on the Pt surface, leading to significant performance degradation. Carbon dioxide and carbonate species (CO3(2-), HCO3(-)) were not observed during 2-propanol oxidation over both electrodes, indicating that the complete oxidation of 2-propanol to CO2 will be a minor reaction.

In Situ Attenuated Total Reflection Infrared Spectroscopy on Electrochemical Ammonia Oxidation over Pt Electrode in Alkaline Aqueous Solutions.

The electrochemical oxidation of ammonia over Pt electrode in alkaline aqueous solutions was studied by in situ attenuated total reflection infrared (ATR-IR) spectroscopy. In 0.1 M NH3-1 M KOH, the band ascribable to the HNH bending mode of adsorbed NH3 was confirmed at 1662-1674 cm(-1) in the potential range of 0.1-1.1 V. The intensity of this band decreased continuously with a rise in potential, indicating the oxidative consumption of adsorbed ammonia. In response to this behavior, the band at 1269 cm(-1) appeared alternatively above 0.2 V, and its intensity reached the local maximal value at ca. 0.4 V. Note that this potential of ca. 0.4 V agreed well with the onset potential of ammonia oxidation, ca. 0.45 V, in the linear sweep voltammogram. This 1269 cm(-1) band was assigned to the NH2 wagging mode of N2H4, which was one of the active intermediates, N2H(x+y,ad) (x = 1 or 2, y = 1 or 2), according to the mechanism proposed by Gerischer and Mauere. To the best of our knowledge, this is the first report for the detection of N2H4 as a reaction intermediate over Pt electrode. Furthermore, the formation of bridged NO was also observed above the onset potential of ammonia oxidation, ca. 0.5 V. Such adsorbed NO species probably inhibit the electrochemical reaction due to the occupation of reaction sites at higher potential.

Drosophila DOCK family protein sponge regulates the JNK pathway during thorax development.

The dedicator of cytokinesis (DOCK) family proteins that are conserved in a wide variety of species are known as DOCK1-DOCK11 in mammals. The Sponge (Spg) is a Drosophila counterpart to the mammalian DOCK3. Specific knockdown of spg by pannir-GAL4 or apterous-GAL4 driver in wing discs induced split thorax phenotype in adults. Reduction of the Drosophila c-Jun N-terminal kinase (JNK), basket (bsk) gene dose enhanced the spg knockdown-induced phenotype. Conversely, overexpression of bsk suppressed the split thorax phenotype. Monitoring JNK activity in the wing imaginal discs by immunostaining with anti-phosphorylated JNK (anti-pJNK) antibody together with examination of lacZ expression in a puckered-lacZ enhancer trap line revealed the strong reduction of the JNK activity in the spg knockdown clones. This was further confirmed by Western immunoblot analysis of extracts from wing discs of spg knockdown fly with anti-pJNK antibody. Furthermore, the Duolink in situ Proximity Ligation Assay method detected interaction signals between Spg and Rac1 in the wing discs. Taken together, these results indicate Spg positively regulates JNK pathway that is required for thorax development and the regulation is mediated by interaction with Rac1.

The Drosophila DOCK family protein sponge is involved in differentiation of R7 photoreceptor cells.

The Drosophila sponge (spg)/CG31048 gene belongs to the dedicator of cytokinesis (DOCK) family genes that are conserved in a wide variety of species. DOCK family members are known as DOCK1-DOCK11 in mammals. Although DOCK1 and DOCK2 involve neurite elongation and immunocyte differentiation, respectively, the functions of other DOCK family members are not fully understood. Spg is a Drosophila homolog of mammalian DOCK3 and DOCK4. Specific knockdown of spg by the GMR-GAL4 driver in eye imaginal discs induced abnormal eye morphology in adults. To mark the photoreceptor cells in eye imaginal discs, we used a set of enhancer trap strains that express lacZ in various sets of photoreceptor cells. Immunostaining with anti-Spg antibodies and anti-lacZ antibodies revealed that Spg is localized mainly in R7 photoreceptor cells. Knockdown of spg by the GMR-GAL4 driver reduced signals of R7 photoreceptor cells, suggesting involvement of Spg in R7 cell differentiation. Furthermore, immunostaining with anti-dpERK antibodies showed the level of activated ERK signal was reduced extensively by knockdown of spg in eye discs, and both the defects in eye morphology and dpERK signals were rescued by over-expression of the Drosophila raf gene, a component of the ERK signaling pathway. Furthermore, the Duolink in situ Proximity Ligation Assay method detected interaction signals between Spg and Rap1 in and around the plasma membrane of the eye disc cells. Together, these results indicate Spg positively regulates the ERK pathway that is required for R7 photoreceptor cell differentiation and the regulation is mediated by interaction with Rap1 during development of the compound eye.

Adaptability of Heteropolytungstate Anions as Efficient Anode Redox Mediators in Redox Flow Polymer Electrolyte Fuel Cells.

Heteropolyanions (HPAs) are known as the candidate for an anode redox mediator for redox flow polymer electrolyte fuel cells (PEFCs). The electrochemical properties of HPAs differ depending on the transition elements and heteroatoms in HPAs. For example, heteropolytungstate anions (W-HPAs), in which the transition element is tungsten, have a lower one-electron reduction potential than other HPAs. Therefore, it has been reported that redox flow PEFCs adapted with W-HPAs exhibit high power generation performance. On the other hand, studies on the heteroatoms of HPAs are limited only to electrochemical properties, and statistical and comprehensive studies on the power generation performance of redox flow PEFCs are lacking. Thus, it is beneficial to clarify the optimal heteroatom in order to design anolytes suitable for redox flow PEFCs. In this study, heteropolytungstate anions with different heteroatoms were adapted as anodic redox mediators in a redox flow PEFC. In power generation tests, the redox flow PEFC with an anolyte of zinctungstate anion showed the highest performance. Zinctungstate anion exhibited the fastest reduction and oxidation rates among the W-HPAs investigated in this study.

Evaluation of the postoperative course of East Asian eyelid reconstruction with free tarsoconjunctival graft transplantation: A Japanese single-centre retrospective study.

Although eyelid reconstruction by transplanting an autologous free tarsoconjunctival graft (FTG) is a well-established technique, few studies have examined the postoperative course of FTG transplantation for East Asian eyelids, including those of Japanese patients. Therefore, this study investigated complication and reoperation rates after FTG transplantation in the reconstruction of East Asian (Japanese) eyelids. This study included 42 eyelids wherein posterior lobe reconstruction after resection of a malignant tumour of the eyelid was performed by FTG transplantation between 2007 and 2019 at Niigata University Medical and Dental Hospital. We investigated complications and need for revision surgery during the patients' postoperative courses. The relationship between postoperative complications, tumour diameter, and eyelid defect width was statistically examined. Of 42 cases reconstructed with FTG, the upper eyelid was reconstructed in 23. Postoperative complications were observed in 12 cases (52%): entropion in eight and corneal epithelial disorder in four. Revision surgery was required in three of those cases (13%). There were 19 cases of lower eyelid reconstruction. Postoperative complications were observed in seven cases (32%): ectropion in three and corneal epithelial disorder in two and one lower eyelid ptosis. Two of these cases (11%) required revision surgery. There was no statistically significant difference in tumour diameter between cases with and without postoperative complications. There was also no significant association between the width of the eyelid defect and the presence/absence of complications. Entropion and ectropion were more likely to occur in the upper and lower eyelids, respectively. For Japanese eyelids, complication rates after FTG transplantation were approximately 50% and 30% for the upper and lower eyelids, respectively. The revision surgery rate was approximately 10% for both upper and lower eyelids. As these revision surgery rates are low, FTG transplantation may be an option for the reconstruction of Japanese eyelids.

Diagnostic value of endoscopic and endoscopic ultrasound characteristics of duodenal submucosal tumour-like heterotopic gastric mucosa.

OBJECTIVE: Recent studies have reported that duodenal heterotopic gastric mucosa (HGM) has been observed in 8.9% of patients who undergo esophagogastroduodenoscopy. However, there are few reports concerning the endoscopic and endoscopic ultrasound characteristics of submucosal tumour-like HGM in the duodenum. METHODS: Endoscopic, endoscopic ultrasound (EUS) and histological findings were analyzed in six patients with submucosal tumour-like HGM, which were confirmed by pathological examination of biopsy or endoscopic polypectomy specimens. RESULTS: Endoscopically, the lesions appeared as a solitary, sessile submucosal tumour-like mass with a depression at the top. In four of six patients, small granular structures were found in the depressed area of the mass. On EUS, all masses demonstrated a heterogeneous pattern, among which four patients presented anechoic areas while two patients showed no anechoic areas. All lesions were localized within the mucosa and submucosa on EUS. Histologically, they consisted of gastric glands and some dilated glands, and were covered with normal duodenal epithelium. In four of six lesions, the tumours were composed of gastric-type foveolar epithelium showing papillary growth, fundic glands and pyloric glands, while the others consisted of gastric-type foveolar epithelium and pyloric glands. CONCLUSION: A heterogeneous pattern on EUS and small granular structures on esophagogastroduodenoscopy represent valuable diagnostic features of submucosal tumour-like HGM.

[A case of ulcerative colitis following smoking cessation].

A 59-year-old man was admitted to our hospital because of watery diarrhea and bloody stool lasting for a month. The patient had been a habitual smoker, smoking 25 cigarettes/day for 35 years. However, he had recently stopped smoking since a giant bulla in the left lung had been found. One month after discontinuing smoking, the patient's symptoms appeared. Colonoscopic examination demonstrated granulated mucosa, edema, and diminished vascular pattern were over the entire colon. Endoscopic and histological findings were compatible with the diagnosis of ulcerative colitis. We reported a case of ulcerative colitis that developed after smoking cessation and discussed the relationship between smoking and ulcerative colitis. Smoking may be associated with ulcerative colitis developed in middle aged person.

Blood-brain barrier permeability analysis of plant ceramides.

Ceramides, a type of sphingolipid, are cell membrane components and lipid mediators that modulate a variety of cell functions. In plants, ceramides are mostly present in a glucosylated glucosylceramide (GlcCer) form. We previously showed that oral administration of konjac-derived GlcCer to a mouse model of Alzheimer's disease reduced brain amyloid-ß and amyloid plaques. Dietary plant GlcCer compounds are absorbed as ceramides, but it is unclear whether they can cross the blood-brain barrier (BBB). Herein, we evaluated the BBB permeability of synthetic plant-type ceramides (4, 8-sphingadienine, d18:2) using mouse and BBB cell culture models, and found that they could permeate the BBB both in vivo and in vitro. In addition, administrated ceramides were partially metabolized to other sphingolipid species, namely sphingomyelin (SM) and GlcCer, while crossing the BBB. Thus, plant ceramides can cross the BBB, suggesting that ceramides and their metabolites might affect brain functions.

[A variety of orbital lymphangioma treatments: one case treated with orbital decompression therapy and the other case with intralesional injection of OK-432 therapy].

BACKGROUND: Orbital lymphangioma can result in ocular emergencies due to acute enlargement, leading to painful proptosis, compressive optic neuropathy, exposure keratopathy, restrictive ocular motility and increased intraocular pressure. Treatment methods and clinical courses of two cases with orbital lymphangioma are reported, one with orbital decompression therapy and the other with intralesional injection of OK-432 therapy. CASE 1: An 8-year-old girl had multilocular cystic orbital intracornal lymphangioma. Emergency operation was deemed necessary because the patient presented with the painful proptosis, the compressive optic neuropathy, and increased intraocular pressure due to acute enlargement, we put the orbital inferior wall was decompressed by inserting an intact inframedial orbital strut. The proptosis vanished completely and visual acuity loss improved. CASE 2: A 2-year-old girl had multilocular cystic orbital intra and extracornal lymphangioma. She had severe proptosis and exposure keratopathy. The extracornal cystic lesion was treated with an intralesional injection of OK-432. On the 7th day after injection, the patient presented with painful severe proptosis. Aspiration of the fluid in the cystic lesion was performed, and the drain was preserved. After the treatment, both the severe proptosis and the exposure keratopathy improved. CONCLUSIONS: Inferior wall decompression was performed on case 1 while keeping the inframedial orbital strut. Although the eye movement disorder was low at the time, the medial and lateral wall decompression improved. In case 2, the extracornal cystic lesion was treated with an intralesional injection of OK-432 Judging from the results of that clinical course, the injection of OK-432 to the intracornal lesion could prove dangerous to the visual performance. Although OK-432 is predictably-effective against lymphangioma, it should not perform be applied without careful consideration.

Ammonia decomposition over Ni catalysts supported on perovskite-type oxides for the on-site generation of hydrogen.

Ammonia decomposition has attracted increasing attention as a promising process for the on-site generation of hydrogen. In this study, Ni catalysts supported on perovskite-type oxides (ABO3) were prepared and the activity for ammonia decomposition was examined. The Ni/ANbO3 (A = Na and K) and Ni/AEMnO3 (AE = Ca, Sr, and Ba) catalysts were less effective for this reaction. Meanwhile, the Ni/REAlO3 (RE = La, Sm, and Gd) catalysts exhibited relatively high activity. For Ni/AETiO3 and Ni/AEZrO3, the performance strongly depended on the A-site element of the perovskite-type oxides, and the Sr and Ba elements were more effective than the Ca one in the respective series. The catalytic activity for Ni/AEZrO3 was higher than Ni/AETiO3 in the case of the same alkaline earth element, and Ni/BaZrO3 was the most active among the samples investigated in this work. For these series, the order in the performance corresponded well with that in the basic property. The nitrogen desorption profiles revealed that the evolution of nitrogen atoms, which is one of the kinetically slow steps, effectively proceeded for Ni/SrZrO3 and Ni/BaZrO3 compared with the conventional Ni catalysts. This promotion effect would be ascribed to the strong basic properties of the SrZrO3 and BaZrO3 supports, resulting in the high activity of Ni/SrZrO3 and Ni/BaZrO3 for ammonia decomposition.

Anion-Exchange Membrane Fuel Cells with Improved CO2 Tolerance: Impact of Chemically Induced Bicarbonate Ion Consumption.

Over the last few decades, because of the significant development of anion exchange membranes, increasing efforts have been devoted the realization of anion exchange membrane fuel cells (AEMFCs) that operate with the supply of hydrogen generated on-site. In this paper, ammonia was selected as a hydrogen source, following which the effect of conceivable impurities, unreacted NH3 and atmospheric CO2, on the performance of AEMFCs was established. As expected, we show that these impurities worsen the performance of AEMFCs significantly. Furthermore, with the help of in situ attenuated total reflection infrared (ATR-IR) spectroscopy, it was revealed that the degradation of the cell performance was primarily due to the inhibition of the hydrogen oxidation reaction (HOR). This is attributed to the active site occupation by CO-related adspecies derived from (bi)carbonate adspecies. Interestingly, this degradation in the HOR activity is suppressed in the presence of both NH3 and HCO3- because of the bicarbonate ion consumption reaction induced by the existence of NH3. Further analysis using in situ ATR-IR and electrochemical methods revealed that the poisonous CO-related adspecies were completely removed under NH3-HCO3- conditions, accompanied by the improvement in HOR activity. Finally, a fuel cell test was conducted by using the practical AEMFC with the supply of NH3-contained H2 gas to the anode and ambient air to the cathode. The result confirmed the validity of this positive effect of NH3-HCO3- coexistence on CO2-tolerence of AEMFCs. The cell performance achieved nearly 95% of that without any impurity in the fuels. These results clearly show the impact of the chemically induced bicarbonate ion consumption reaction on the realization of highly CO2-tolerent AEMFCs.

Polymer Electrolyte Fuel Cells Employing Heteropolyacids as Redox Mediators for Oxygen Reduction Reactions: Pt-Free Cathode Systems.

In this study, the heteropolyacids of H3+xPVxMO12-xO40 (x = 0, 2, and 3) were applied as redox mediators for the oxygen reduction reaction in polymer electrolyte fuel cells, of which the cathode is free from the usage of noble metals such as Pt/C. In this system, the electrochemical reduction of heteropolyacid over the carbon cathode and the subsequent reoxidation of the partially reduced heteropolyacid by exposure to the dissolved oxygen in the regenerator are important processes for continuous power generation. Thus, the redox properties of catholytes containing these heteropolyacids were investigated in detail. The substitution quantity of V in the heteropolyacid affected the onset reduction potential as well as the reduction current density, resulting in a difference in cell performance. The chemical composition of heteropolyacid also had a significant impact on the reoxidation property. Among the three compounds, H6PV3Mo9O40 was the most suitable redox mediator. Furthermore, the pH of the catholyte was found to be the crucial factor in determining the reoxidation rate of partially reduced heteropolyacid as well as cell performance.

Alpha-fetoprotein (AFP)- and des-gamma-carboxy prothrombin (DCP)-producing adenocarcinoma of the stomach with liver metastasis in a patient with chronic hepatitis C.

A 45-year-old man was admitted to our hospital because of chronic hepatitis C and a large liver tumor accompanied by increased serum levels of alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP), the tumor markers for hepatocellular carcinoma. Endoscopic examination revealed advanced gastric cancer. Biopsy specimens of the stomach and liver showed gastric adenocarcinoma and its metastasis to the liver. Immunohistochemical studies demonstrated that adenocarcinoma cells both of the stomach and liver, were positive for the antibodies against AFP as well as DCP. Expression of AFP mRNA was shown in the cancer cells of the stomach. Accordingly, we diagnosed this patient with AFP- and DCP-producing adenocarcinoma of the stomach together with liver metastasis.

A Stability Study of Ni/Yttria-Stabilized Zirconia Anode for Direct Ammonia Solid Oxide Fuel Cells.

In recent years, solid oxide fuel cells fueled with ammonia have been attracting intensive attention. In this work, ammonia fuel was supplied to the Ni/yttria-stabilized zirconia (YSZ) cermet anode at 600 and 700 °C, and the change of electrochemical performance and microstructure under the open-circuit state was studied in detail. The influence of ammonia exposure on the microstructure of Ni was also investigated by using Ni/YSZ powder and Ni film deposited on a YSZ disk. The obtained results demonstrated that Ni in the cermet anode was partially nitrided under an ammonia atmosphere, which considerably roughened the Ni surface. Moreover, the destruction of the anode support layer was confirmed for the anode-supported cell upon the temperature cycling test between 600 and 700 °C because of the nitriding phenomenon of Ni, resulting in severe performance degradation.

Electrochemical and catalytic properties of Ni/BaCe0.75Y0.25O3-δ anode for direct ammonia-fueled solid oxide fuel cells.

In this study, Ni/BaCe0.75Y0.25O3-δ (Ni/BCY25) was investigated as an anode for direct ammonia-fueled solid oxide fuel cells. The catalytic activity of Ni/BCY25 for ammonia decomposition was found to be remarkably higher than Ni/8 mol % Y2O3-ZrO2 and Ni/Ce0.90Gd0.10O1.95. The poisoning effect of water and hydrogen on ammonia decomposition reaction over Ni/BCY25 was evaluated. In addition, an electrolyte-supported SOFC employing BaCe0.90Y0.10O3-δ (BCY10) electrolyte and Ni/BCY25 anode was fabricated, and its electrochemical performance was investigated at 550-650 °C with supply of ammonia and hydrogen fuel gases. The effect of water content in anode gas on the cell performance was also studied. Based on these results, it was concluded that Ni/BCY25 was a promising anode for direct ammonia-fueled SOFCs. An anode-supported single cell denoted as Ni/BCY25|BCY10|Sm0.5Sr0.5CoO3-δ was also fabricated, and maximum powder density of 216 and 165 mW cm(-2) was achieved at 650 and 600 °C, for ammonia fuel, respectively.