Decoration of Gold and Platinum Nanoparticle Catalysts by 1 nm Thick Metal Oxide Overlayer and Its Effect on the CO Oxidation Activity.

Exfoliated M-Al layered double hydroxide (M-Al LDH; M = Mg, Co, Ni, and Zn) nanosheets were adsorbed on Au/SiO2 and calcined to transform LDH into mixed metal oxides (MMOs) and yield Au/SiO2 coated with a thin MMO overlayer. These catalysts showed a higher catalytic activity than pristine Au/SiO2. In particular, the 50% CO conversion temperature decreased by more than 250 °C for Co-Al MMO-coated Au/SiO2. In contrast, the deposition of CoAlOx on Au/SiO2 by impregnation or the deposition of Au on Co-Al MMO-coated SiO2 resulted in a worse catalytic activity. Moreover, the presence of a thick MMO overlayer decreased the catalytic activity, suggesting that the control of the overlayer thickness to less than 1 nm is a requisite for obtaining a high catalytic activity. Moreover, the thin Co-Al MMO overlayer on Au/SiO2 possessed abundant oxygen vacancies, which would play an important role in O2 activation, resulting in a highly active interface between Au and the defect-rich MMO on the Au NP surface. Finally, this can be applied to Pt/SiO2, and the obtained Co-Al MMO-coated Pt/SiO2 also exhibited a much improved catalytic activity for CO oxidation.

Gold/Substituted Hydroxyapatites for Oxidative Esterification: Control of Thin Apatite Layer on Gold Based on Strong Metal-Support Interaction (SMSI) Results in High Activity.

Gold nanoparticles (Au NPs) deposited on various cation- and anion-substituted hydroxyapatites (Au/sHAPs) show oxidative strong metal-support interaction (SMSI), wherein a thin layer of the sHAP covered the surface of the Au NPs by heat treatment in an oxidative atmosphere. Calcination of Au/sHAPs at 300 °C caused a partial SMSI and that at 500 °C gave fully encapsulated Au NPs. We investigated the influence of the substituted ions in sHAP and the degree of the oxidative SMSI on the catalytic performance of Au/sHAPs for oxidative esterification of octanal or 1-octanol with ethanol to obtain ethyl octanoate. The catalytic activity depends on the size of the Au NPs but not on the support used, owing to the similarity of the acid and base properties of sHAPs except for Au/CaFAP. The presence of a large number of acidic sites on CaFAP lowered the product selectivity, but all other sHAPs exhibited similar activity when the Au particle size was almost the same, owing to the similarity of the acid and base properties. Au/sHAPs_O2 with SMSI exhibited higher catalytic activity than Au/sHAPs_H2 without SMSI despite the fact that the number of exposed surface Au atoms was decreased by the SMSI. In addition, the oxidative esterification reaction proceeded even though the Au NPs were fully covered by the sHAP layer when the thickness of the layer was controlled to be less than 1 nm. The substrate can access the surfaces of the Au NPs covered by the thin sHAP layer (<1 nm), and the presence of the sHAP structure in close contact with the Au NPs resulted in significantly higher catalytic activity compared with that for fully exposed Au NPs deposited on the sHAPs. This result suggests that maximizing the contact area between the Au NPs and the sHAP support based on the SMSI enhances the catalytic activity of Au.

Hemostasis using a covered self-expandable metal stent for pseudoaneurysm bleeding from the perihilar bile duct.

Although there are many reports of hemostasis with covered self-expandable metal stent (CSEMS) for bleeding from the papilla of Vater and the intrapapillary and distal bile duct, there are rare reports of its use for hemostasis in the perihilar bile duct. We report the case of a patient undergoing supportive care for perihilar cholangiocarcinoma with acute cholecystitis after side-by-side placement of uncovered SEMS for perihilar bile duct obstruction. Percutaneous transhepatic gallbladder aspiration was performed upon admission, and hematemesis occurred the next day. Since computed tomography scanning showed a pseudoaneurysm in the right uncovered SEMS, hemostasis by interventional radiology (IVR) was performed thrice for massive bleeding; however, hemostasis could not be achieved. When endoscopic retrograde cholangiopancreatography was performed for scrutiny and treatment of melena and increased hepatobiliary enzyme, the endoscopic visual field could not be secured by bleeding, and changes in hemodynamics were observed; thus, IVR was required, but it was difficult to perform. Since bleeding from the right bile duct was expected, hemostasis was performed using CSEMS. This is the first report of hemostasis performed by placing a covered SEMS for bleeding from a pseudoaneurysm of the intrahepatic bile duct.

Muscular Metastasis of Hepatocellular Carcinoma: Case Report and Literature Review.

There are few case reports of hepatocellular carcinoma (HCC) metastasis to the skeletal muscle. A 78-year-old man developed a mass in the right shoulder. Washout of contrast medium during contrast-enhanced ultrasonography (CEUS) in both the primary HCC and the metastatic site was detected. Several nodules were scattered throughout the liver on an autopsy. In addition, the moderately differentiated HCC had metastasized to the right teres major muscle. Rare muscular metastasis should be considered if a hepatic tumor is moderately or poorly differentiated HCC. Early washout during CEUS is consistent with a pathological diagnosis of moderately or poorly differentiated HCC.

Primary endoscopic bile duct stone removal for severe acute cholangitis: a retrospective study.

INTRODUCTION: While the Tokyo Guidelines 2018 suggest primary stone removal for mild to moderate cholangitis, a guideline for severe acute cholangitis is not mentioned. We, therefore, investigated the clinical outcomes of patients with severe acute cholangitis to confirm the usefulness and safety of primary stone removal. METHOD: This study included 104 severe acute cholangitis patients without gallstone pancreatitis diagnosed at our institution between January 2014 and December 2020. Patients with percutaneous transhepatic biliary drainage as the primary drainage, bile duct stenosis, and endoscopically unidentified bile duct stones were excluded from this study. The clinical results of 14 patients with primary stone removal (primary group) and 23 patients with elective stone removal (elective group) were then retrospectively examined (excluding abnormal values due to underlying diseases). RESULTS: Upon comparing the patient characteristics between groups, the elective group had significantly higher cardiovascular dysfunction (57% vs 7%; p = 0.004), septic shock (39% vs 0%; p = 0.006), disseminated intravascular coagulation treatment (57% vs 14%; p = 0.016), and positive blood cultures (91% vs 43%; p = 0.006) than those in the primary group. Endoscopic sphincterotomy for naïve papilla (90% vs 21%; p = 0.01) and endoscopic nasobiliary drainage (50% vs 9%; p = 0.014) were higher in the primary group, while endoscopic biliary stenting (7% vs 87%; p < 0.001) was lower than that in the elective group. DISCUSSION: There were no significant differences in adverse events or complete stone removal rates between the two groups. In the primary group, the period from the first endoscopic retrograde cholangiopancreatography to stone removal (0 days vs 12 days; p < 0.001) and hospitalization period (12 days vs 26 days; p = 0.012) were significantly shorter and the hospitalization cost ($7731 vs $18758; p < 0.001) was significantly lower than those in the elective group. CONCLUSION: If patients are appropriately selected, bile duct stones may be safely removed for the treatment of severe acute cholangitis.

Selenium deficiency activates mouse liver Nrf2-ARE but vitamin E deficiency does not.

Selenium (Se) and vitamin E are antioxidant micronutrients. Se functions through selenoproteins and vitamin E reacts with oxidizing molecules in membranes. The relationship of these micronutrients with the Nrf2-antioxidant response element (ARE) pathway was investigated using ARE-reporter mice and Nrf2-/- mice. Weanling males were fed Se-deficient (0 Se), vitamin E-deficient (0 E), or control diet for 16 or 22 weeks. The ARE reporter was elevated 450-fold in 0 Se liver but was not elevated in 0 E liver. Antioxidant enzymes induced by Nrf2-ARE (glutathione S-transferase (GST), NAD(P)H quinone oxidoreductase (NQOR), and heme oxygenase-1 (HO-1)) were elevated in 0 Se livers but not in 0 E livers. Deletion of Nrf2 had varying effects on the inductions, with GST induction being abolished by it but induction of NQOR and HO-1 still occurring. Thus, Se deficiency, but not vitamin E deficiency, induces a number of enzymes that protect against oxidative stress and modify xenobiotic metabolism through Nrf2-ARE and other stress-response pathways. We conclude that Se deficiency causes cytosolic oxidative stress but that vitamin E deficiency does not. This suggests that the oxidant defense mechanisms in which these antioxidant nutrients function are independent of one another.

Effect of attractive interaction on instability of pedestrian flow in a two-dimensional optimal velocity model.

We incorporate an attractive interaction in a two-dimensional optimal velocity model and investigate the stability of homogeneous flow in the linear approximation. There exists a different type of instability in this model. We show the phase diagram and the behavior of the flow in each phase by numerical simulations. A new phase due to the new instability appears at low density, and the instability can be a candidate of the group formation mechanism of organisms.

Instability of pedestrian flow and phase structure in a two-dimensional optimal velocity model.

A two-dimensional optimal velocity model was proposed for the study of pedestrian and granular flow. We investigate the stability of homogeneous flow in the linear approximation and show the phase diagram of the model. We also investigate the property of the model by numerical simulation in the cases of unidirectional and counter flow. From these results, we present a unified understanding of the behavior of pedestrians and other related systems.

Equivalence of linear response among extended optimal velocity models.

We investigate the property of extended optimal velocity (OV) models of traffic flow, in which a driver looks at arbitrary number of vehicles that precede. We prove an equivalence of linear response among extended models. This equivalence provides a natural understanding of the improvement of the stability of traffic flow.

Dynamical model of a cooperative driving system for freeway traffic.

We propose an extended optimal velocity model applicable to cooperative driving control system, which will be realized in the near future. In the model, a vehicle is controlled by the system using the information of arbitrary number of vehicles that precede or follow. We investigate the stability of uniform flow and the response to a disturbance in the linear approximation.

Effect of looking at the car that follows in an optimal velocity model of traffic flow.

An extension of an optimal velocity model is proposed. In the new model, a driver looks at the following car as well as the preceding car. We introduce an additional optimal velocity function that depends on the headway of the following car. We investigate the effect of looking back at the car that follows and show that this extension effectively stabilizes the traffic flow.

Meandering instability in two-dimensional optimal velocity model for collective motion of self-propelled particles.

We investigate the stability of a uniform flow of self-propelled particles in a two-dimensional optimal velocity model. As an initial condition, the particles are distributed uniformly in a narrow region of the space. This condition corresponds to a migration of organisms. It is found that the uniform flow is unstable and a meandering motion appears by numerical simulations. We also show the instability exists for any values of parameters by the linear analysis. It means that there is no stable uniform flow in this model.

Molecular mechanism of antidiabetic zinc-allixin complexes: regulations of glucose utilization and lipid metabolism.

We previously reported new zinc complexes of allixin [bis(allixinato)zinc] and its derivative bis(thioallixin-N-methyl)zinc that demonstrated excellent antidiabetic activity in type 2 diabetic mellitus KKA(y) mice. However, the molecular mechanism of these complexes is not fully understood. Thus, we attempted to reveal the intracellular mechanism of these complexes in 3T3-L1 adipocytes. Both zinc complexes induced Akt/protein kinase B (Akt/PKB) phosphorylation. The phosphorylation of Akt/PKB enhanced glucose transporter 4 translocation to the plasma membrane; this in turn enhanced the glucose utilization in a dose- and time-dependent manner. Glucose utilization by the complexes depended on the intracellular zinc concentration. Moreover, zinc complexes suppressed the cyclic AMP dependent protein kinase mediated phosphorylation of hormone-sensitive lipase (HSL), leading to the inhibition of free fatty acid release from the 3T3-L1 adipocytes. Such responses were inhibited by wortmannin, suggesting that the suppression of HSL by zinc complexes was dependent in the phosphoinositide 3-kinase-Akt/PKB signaling cascade. On the basis of these results, we proposed that both zinc complexes activated the Akt/PKB-mediated insulin-signaling pathway and improved both glucose utilization and lipid metabolism.

Action mechanism of bis(allixinato)oxovanadium(IV) as a novel potent insulin-mimetic complex: regulation of GLUT4 translocation and FoxO1 transcription factor.

Bis(allixinato)oxovanadium(IV), VO(alx)(2) (alx is 3-hydroxy-5-methoxy-6-methyl-2-pentyl-4-pyrone), has been reported to act as an antidiabetic agent in streptozotocin-induced type-1-like and obesity-linked KKA(y) type 2 diabetic model mice. VO(alx)(2) is also proposed as a candidate agent for treating metabolic syndromes in animals. However, its functional mechanism is yet to be clarified. In this study, we examined whether VO(alx)(2) contributes to both the activation of the insulin signaling cascade that activates glucose transporter 4 (GLUT4) translocation and the regulation of the forkhead box O1 (FoxO1) transcription factor that controls the gene transcription of gluconeogenesis genes. The following three important results were obtained: (1) intracellular vanadium concentration in 3T3-L1 adipocytes is higher after treatment with VO(alx)(2) than with VOSO(4); (2) VO(alx)(2) stimulates the translocation of GLUT4 to the plasma membrane following activation of the tyrosine phosphorylation of the insulin receptor beta-subunit (IRbeta) and insulin receptor substrate (IRS) as well as Akt kinase in 3T3-L1 adipocytes; and (3) the mechanism of inhibition of glucose-6-phosphatase (G6Pase) catalytic subunit gene expression by vanadium is due to disruption of FoxO1 binding with the G6Pase promoter, which indicates that FoxO1 is phosphorylated by VO(alx)(2)-stimulated Akt in HepG2 cells. On the basis of these results, we propose that the critical functions of VO(alx)(2) involve the activation of phosphatidylinositol 3-kinase-Akt signaling through the enhancement of tyrosine phosphorylation of IRbeta and IRS, which in turn transmits the signal to activate GLUT4 translocation, and the regulation of the DNA binding activity of the FoxO1 transcription factor.

All regions of mouse brain are dependent on selenoprotein P for maintenance of selenium.

The brain and testis retain selenium better than other tissues during selenium deficiency. Studies of mice with selenoprotein P (Sepp1) deleted (Sepp1(-/-) mice) showed that brain and testis selenium levels are largely dependent on Sepp1. Therefore, we examined tissue selenium in mice fed varying amounts of selenium and in Sepp1(-/-) mice to characterize better the role(s) of Sepp1. Mice were fed a selenium-deficient diet for 8 wk supplemented with selenium as selenite from none to 0.25 mg/kg diet and tissue selenium was measured. Brain and testis maintained their selenium better than did liver, kidney, and muscle when dietary selenium was limiting but testis selenium fell sharply in the group fed the deficient diet. Brain retained its selenium well, even in the group fed the deficient diet. After intravenous injection of (75)Se-Sepp1 into Sepp1(-/-) and Sepp1(+/+) mice, qualitative differences between brain and testis (75)Se uptake were noted, further suggesting differences in their uptake of selenium from Sepp1. Finally, selenium was measured in brain regions of Sepp1(-/-) and Sepp1(+/+) mice fed the diet supplemented with 1 mg selenium/kg and Sepp1(+/+) mice fed the deficient diet. Deletion of Sepp1 and selenium deficiency each lowered selenium a similar amount in cortex, midbrain, brainstem, and cerebellum. Selenium in the hippocampus was lowered by deletion of Sepp1 but not by selenium deficiency. These results suggest that Sepp1 is more important for maintaining selenium in the hippocampus than in other brain regions. They also confirm the position of the brain at the apex of the organ selenium hierarchy.

Serum iron increases with acute induction of hepatic heme oxygenase-1 in mice.

Heme oxygenase (HO)-1 is induced by oxidative stress and protects against oxidant injury. We examined the effect of rapid induction of hepatic HO-1 on serum iron level. Serum iron was approximately doubled within 6 h when HO-1 was induced by phenobarbital treatment of selenium-deficient mice. Blocking heme synthesis with diethyl 1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate (DDC) prevented the induction of HO-1 and the rise in serum iron. DDC did not block HO-1 induction by hemin. Inhibition of HO activity by tin protoporphyrin prevented a rise in serum iron that occurred following phorone treatment. These results indicate that heme synthesis or an exogenous source of heme is needed to allow induction of HO-1. Further, they link HO-1 induction with a rise in serum iron, suggesting that the iron resulting from catabolism of heme by HO-1 is released by the liver.

An improved diagnostic method for chronic hepatic disorder: analyses of metallothionein isoforms and trace metals in the liver of patients with hepatocellular carcinoma as determined by capillary zone electrophoresis and inductively coupled plasma-mass spectrometry.

It is desirable to diagnose hepatocellular carcinoma (HCC) in the early stages during its development since its treatment is usually difficult. We previously proposed a new diagnostic method that made use of the total metallothionein (MT), zinc (Zn), and copper (Cu) concentrations in the liver of the HCC patients. We recently found that MT-1 is involved in the metabolism or detoxification of toxic metals, such as cadmium; on the other hand, MT-2 is responsible for the homeostasis of essential metals such as copper, in experimental models such as Long Evans Cinnamon (LEC) rats. In order to device a better diagnostic method than the one we proposed previously, in this study, we newly propose an improved method that includes the discriminative determination data regarding the MT isomers, namely, MT-1 and MT-2, in the liver of patients with or without HCC as compared with the total MT level. The total MT and Zn concentrations in the HCC patients were confirmed to be significantly lower than those in patients without hepatic disorders (Ctrl). In contrast, Cu concentrations of the HCC patients were higher than those of the Ctrl patients. In addition, in the juxta-tumor portion with HCC, MT-1 concentrations were significantly higher than those of MT-2. In contrast, the MT-1 concentrations in the tumor portion were significantly lower than that in the juxta-tumor portion. In addition, MT-1/MT-2 ratio in the tumor portion was significantly lower than that of the juxta-tumor portion. By using parameters such as concentrations of Cu, Zn, total MT, and MT isomers, we performed the multivariate discriminative analysis (MDA). The results suggest that the concentrations of MT isomers change depending on the progress of the tumor, and information on MT isomers and trace elements is very useful in determining the stage of the chronic hepatic disorder.

A new diagnostic method for chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma based on serum metallothionein, copper, and zinc levels.

Serum metal levels and their ratios are frequently reported to be good signals for diagnosing various diseases. These parameters are not always specific to the disease, however, it is necessary to use other serum parameters for an exact diagnosis. We examined whether the monitoring of these serum parameters such as metallothionein, copper, and zinc levels are useful in diagnosing hepatic disorders. Metallothionein levels of patients with liver cirrhosis and hepatocellular carcinoma were found to be significantly lower than those of patients with chronic hepatitis and those of controls. In contrast, copper levels of the patients with liver cirrhosis and hepatocellular carcinoma were significantly higher than those with chronic hepatitis and controls. Zinc levels of the patients with chronic hepatitis and hepatocellular carcinoma were lower than those of controls. Using these three parameters, we are introducing a new parameter, (Cu/Zn)/MT, by which we can discriminate between patients in the [control+miscellaneous diseases+chronic hepatitis] group and those in the [liver cirrhosis+hepatocellular carcinomal group. The new parameter does not, however, allow us to clearly distinguish between the liver cirrhosis and hepatocellular carcinoma groups. Multivariate discriminant analysis was found to be very useful, with combinations of two discriminant functions having been designed to discriminate both between chronic hepatitis and liver cirrhosis and between liver cirrhosis and hepatocellular carcinoma. This method recognizes the differences between hepatic disorder, including chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma groups. On the basis of these results, we propose here that the diagnosis of hepatic disorders should be made based on a combination of three serum levels such as those of metallothionein, copper, and zinc.

Implication of the differential roles of metallothionein 1 and 2 isoforms in the liver of rats as determined by polyacrylamide-coated capillary zone electrophoresis.

Metallothioneins (MTs), determined by polyacrylamide-coated capillary zone electrophoresis (CZE), coincided well with those described by enzyme-linked immunosorbent assay. By using CZE, MT isoforms 1 (MT-1) and 2 (MT-2) were well separated and determined in the liver cytosol of LEC rats and Wistar rats administered CdCl(2). The total concentrations of MTs in the liver cytosol of LEC rats increased age-dependently as 1.0, 2.1, and 7.2mg/g wet weight of the liver at the age of 5, 10, and 15 weeks, respectively, and those of Wistar rats that had received daily CdCl(2) also increased with time of CdCl(2) as 0.5 and 1.2mg/g wet weight of the liver for 3 and 6 consecutive administration days, respectively. The MT-1/MT-2 ratio in the liver cytosol of LEC rats decreased age-dependently as 1.75, 1.49, and 0.76 at the age of 5, 10, and 15 weeks, respectively. In contrast, that of Wistar rats increased with time of exposure to the metal ion CdCl(2) as 1.1 and 1.6 for 3 and 6 administration days, respectively. Copper accumulation in the liver of LEC rats has already been reported. The present results indicated that the mechanism of the induction of MT synthesis differs between LEC rats, who lack ATP7B, and Wistar rats, who were given a toxic metal ion. On the basis of these results, we propose that MT-1 is related to the metabolism or detoxification of toxic metals such as Cd, and in contrast, MT-2 is responsible for the homeostasis of essential metals such as Cu.