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Background: The importance of the role of NF-κB is recognized in situations such as malignant transformation and metastasis of cancer, and it has been suggested that inhibiting this role can be one of the cancer treatment strategies. Gold preparations such as auranofin are known to have an indirect NF-κB inhibitory effect. Objective: We synthesized a novel gold complex [tiopronin monovalent gold-5-mercapto- 1-methyl tetrazole, abbreviated as TPN-Au(I)-MM4], with different physical properties and chemical structure from auranofin, and evaluated its cytotoxic activity and radiation sensitizing effect on human THP1 cells. Methods: The number of viable cells was counted by the trypan blue dye exclusion method. The cell death evaluation was performed by FITC-Annexin V+ and PI staining. In investigating the radiation sensitizing effect of TPN-Au(I)-MM4, this compound [10 or 25 μM] was added into the culture medium 1 h before X-ray irradiation. Results: In the cells treated with 25 μM TPN-Au(I)-MM4 for 72 h, a decrease in the proliferation of THP1 cells was observed [The relative values of viable cells in the control group and the 25 μM treatment group were approximately 6.8 and 4.2, respectively]. In the combination of 25 μM of the compound treatment and X-ray irradiation, an increase of approximately 3.0-fold was observed in 2 Gy irradiation and approximately 1.4-fold in 4 Gy irradiation as in comparison to the case of irradiation alone. Conclusion: These results suggest that TPN-Au(I)-MM4 reduces the proliferation of THP1 cells through the induction of cell death, and the combined use of TPN-Au(I)-MM4 and X-ray irradiation shows effective cytotoxicity against THP1 cells.

Aim Improving cholesterol efflux capacity (CEC) of high-density lipoprotein (HDL) has been regarded as a novel target for preventing cardiovascular disease. HDL reportedly has antioxidant properties which may contribute to its functions. We investigated changes in CEC with intake of the Japan Diet (JD) recommended by the Japan Atherosclerosis Society and the relationship of these changes to serum antioxidant concentrations. Methods A randomized parallel controlled clinical trial on JD intake was performed in Japanese patients with dyslipidemia. Ninety-eight participants were randomly divided into the JD (n=49) or the partial JD (PJD) (n=49) group. Nutrition education, based on each diet at baseline and at 3 months, was provided and the participants were followed up for 6 months. Results Mean CEC was 1.05 in total and correlated positively with HDL-cholesterol (p＜0.001) at baseline. CEC did not change while oxygen radical absorbance capacity (ORAC) was decreased in both groups (p＜0.001). Although serum total carotenoid increased in both groups, serum α-tocopherol decreased in the JD group as compared to the PJD group (p＜0.05). CEC correlated positively with HDL ORAC at baseline (p=0.021) and with serum total carotenoid at 3 and 6 months (p=0.005, 0.035). Changes in CEC correlated positively with changes in HDL ORAC at 3 months and serum total tocopherol at 3 and 6 months (p＜0.001). Conclusion CEC was not changed by JD education in Japanese patients with dyslipidemia who already had normal CEC at baseline. CEC was suggested to be positively associated with serum α- and γ-tocopherol and HDL ORAC.

There is limited information available about the physiological content of glyceraldehyde, a precursor of toxic advanced glycation end products. The conventional derivatization method for aldoses using 1-phenyl-3-methyl-5-pyrazolone did not allow reproducible quantification of glyceraldehyde due to the instability of glyceraldehyde compared to other aldoses. We optimized the derivatization condition to achieve high and reproducible recovery of derivatives for liquid chromatography tandem mass spectrometry quantification. Based on the stability of glyceraldehyde during sample preparation and high recovery of spiked standard, the present method provides reproducible quantification of glyceraldehyde in the body. The glyceraldehyde contents in fasting conditions in the rodent liver (mice: 50.0 ± 3.9 nmol/g; rats: 35.5 ± 4.9 nmol/g) were higher than those in plasma (9.4 ± 1.7 and 7.2 ± 1.2 nmol/mL). The liver glyceraldehyde levels significantly increased after food consumption (p < 0.05) but remained constant in the plasma. High fat diet feeding significantly increased plasma glyceraldehyde levels in mice (p < 0.005). In healthy human volunteers, the plasma glyceraldehyde levels remained unchanged after the consumption of steamed rice. In patients with type 2 diabetes, the plasma glyceraldehyde level was positively correlated with the plasma glucose level (r = 0.84; p < 0.0001).

Staphylococcus epidermidis are gram-positive bacteria that form a biofilm around implanted devices and develop an infection into a chronic state. Recently, it has been revealed that microvesicles have important roles in biofilm formation and intercellular communication among bacteria. However, biofilm formation of Staphylococcus epidermidis, and its relation to microvesicle secretion, is poorly understood because of the difficulty required to preserve the delicate water-rich morphology of biofilm for high-resolution observations. Here, we successfully imaged the microvesicles secreted from Staphylococcus epidermidis and the subsequent process of their integration into biofilm using liquid-phase imaging using atmospheric scanning electron microscopy (ASEM). In the biofilm, cells were connected by nanotube-like structures attached by microvesicles, and surrounded by extracellular polymeric substances. Cells cultured in the ASEM specimen holder were aldehyde-fixed and stained using positively charged nanogold labelling and/or using National Center for Microscopy and Imaging Research method. The samples immersed in aqueous radical scavenger glucose buffer were imaged by the inverted SEM of ASEM. Information regarding the morphologies of microvesicles, nanotube-like fibrils, and biofilm formed by Staphylococcus epidermidis is expected to be useful to elucidate the biological mechanism of biofilm formation and to develop a medicine against biofilms and their associated infections.

Lymphodepleting cytotoxic regimens enhance the antitumor effects of adoptively transferred effector and naive T cells. Although the mechanisms of antitumor immunity augmentation by lymphodepletion have been intensively investigated, the effects of lymphodepletion followed by T cell transfer on immune checkpoints in the tumor microenvironment remain unclear. The current study demonstrated that the expression of immune checkpoint molecules on transferred donor CD4+ and CD8+ T cells was significantly decreased in lymphodepleted tumor-bearing mice. In contrast, lymphodepletion did not reduce immune checkpoint molecule levels on recipient CD4+ and CD8+ T cells. Administration of anti-PD-1 antibodies after lymphodepletion and adoptive transfer of T cells significantly inhibited tumor progression. Further analysis revealed that transfer of both donor CD4+ and CD8+ T cells was responsible for the antitumor effects of a combination therapy consisting of lymphodepletion, T cell transfer and anti-PD-1 treatment. Our findings indicate that a possible mechanism underlying the antitumor effects of lymphodepletion followed by T cell transfer is the prevention of donor T cell exhaustion and dysfunction. PD-1 blockade may reinvigorate exhausted recipient T cells and augment the antitumor effects of lymphodepletion and adoptive T cell transfer.

Impairment of inferior olivary neurons (IONs) affects whole-body movements and results in abnormal gait and posture. Because IONs are activated by unpredicted motion rather than regular body movements, the postural dysfunction caused by ION lesions is expected to involve factors other than simple loss of feedback control. In this study, we measured the postural movements of rats with pharmacological ION lesions (IO rats) trained to stand on their hindlimbs. The coordination of body segments as well as the distribution and frequency characteristics of center of mass (COM) motion were analyzed. We determined that the lesion altered the peak properties of the power spectrum density of the COM, whereas changes in coordination and COM distribution were minor. To investigate how the observed properties reflected changes in the control system, we constructed a mathematical model of the standing rats and quantitatively identified the control system. We found an increase in linear proportional control and a decrease in differential and nonlinear control in IO rats compared with intact rats. The dystonia-like changes in body stiffness explain the nature of the linear proportional and differential control, and a disorder in the internal model is one possible cause of the decrease in nonlinear control.

Electrophoresis is one of the major techniques to analyze macromolecular structure and interaction. Its capability depends on the sensitivity and specificity of the staining methods. We have here examined silver staining of proteins and nucleic acids separated by agarose native gel electrophoresis. By comparing five commercial kits, we identified Silver Stain Plus from Bio-Rad most adequate, as it provided little background staining and reasonable band staining. One of the disadvantages of the Silver Stain Plus kit is its variable staining of glycoproteins as tested with several model samples, including hen egg white proteins, α1-acid glycoprotein and SARS-CoV-2 Spike protein. One of the advantages of silver staining is its ability to stain nucleic acids as demonstrated here for a model nucleic acid with two kits. It was then used to monitor the removal of nucleic acids from the affinity-purified maltose binding protein and monoclonal antibody. It also worked well on staining proteins on agarose gels prepared in the vertical mode, although preparation of the vertical agarose gels required technological modifications described in this report. With the silver staining method optimized here, it should be possible in the future to analyze biological samples that may be available in limited quantity.

In this study, the influence of primer contamination on enamel bonding was analyzed. Adper Scotchbond Multi-Purpose (SMP), CLEARFIL SE Bond 2 (SE2), Scotchbond Universal (SBU) Adhesive, and Scotchbond Etchant (35% phosphoric acid; PA) were used. Ground bovine enamels were divided into eight groups based on the bonding protocols. The bonding interfaces after an acid-base challenge were observed via scanning electron microscopy to determine the acid-base resistant zone (ABRZ). Moreover, the bonding interfaces after the nanoleakage challenge were analyzed via energy-dispersive X-ray spectroscopy. ABRZ was observed in all the samples except PA_ONLY (applied PA etching, No primer and No adhesive resin). The funnel-shaped erosion was detected only in X_SBU (applied SBU without PA etching). The nanoleakage test revealed silver patterns in some groups. The nanoleakage, i.e., the penetration of the silver ions, was detected in the groups wherein primer was applied on PA-pre-etched enamel.

We revealed that hydrogen (H) in pure Fe promotes grain refinement during plastic deformation, which is caused by the increase in dislocation density by the shielding effect and the presence of vacancy-H clusters. The promotion effect of H was dependent on the temperature and the strain rate, which is considered to result from a change in the number density of vacancy-H clusters and the magnitude of shielding effect by H.

To visualize whole cancerous region including hypoxic cancer without radiation exposure, we developed meglumine-gadopentetate-glucose solution for 7.0-T magnetic resonance imaging. The infusion solution consists of meglumine-gadopentetate and glucose solutions, and these solutions are mixed before the vein drip infusion. We used readily available solutions, and the concentrations of the meglumine-gadopentetate and glucose solutions were 37.14 and 5.0%, respectively. In the first and second experiments, vein infusions were conducted from a rabbit ear using meglumine-gadopentetate-saline and meglumine-gadopentetate-glucose solutions, and T1 weighted imaging was performed to visualize cancerous region. Using the meglumine-gadopentetate saline, it was not difficult to image cancer-growth regions with new blood vessels. Using the meglumine-gadopentetate-glucose solution, the signal intensity of whole cancerous region including hypoxic cancer substantially increased. The visualizing duration for the meglumine gadopentetate glucose was beyond 90 min, and the rabbit survived after the infusion. The signal intensity in the hypoxic cancer was increasing until 90 min using the meglumine-gadopentetate-glucose solution, since the meglumine-gadopentetate molecules were absorbed into almost the whole cancerous region along with glucose-molecule flows.

Increased plant phosphorus uptake and growth as a result of inoculation with arbuscular mycorrhizal (AM) fungi is observed less often under field conditions than in pot experiments. Interaction between introduced and indigenous AM fungi is one of the reasons for ineffectiveness of inoculation in the field. We aimed to distinguish the effect of introduced and indigenous AM fungi on phosphorus uptake and growth of Allium fistulosum in a field experiment. Superphosphate was applied in the ratio of 0 or 317 P kg ha−1 to the plots fumigated with or without dazomet that is a common soil fumigant. Seedlings of A. fistulosum that had been inoculated with or without Rhizophagus spp. strain R-10 were transplanted into the plots. AM fungal colonization, OTU read abundance of indigenous and introduced AM fungi, shoot P concentration, and shoot growth were measured at 31, 60, 90, and 131 days after transplanting (DAT). We could partially separate the effects of introduced AM fungi from indigenous AM fungi by fumigation with dazomet. Though neither inoculation nor P level affected shoot fresh weight and shoot P content in the non-fumigated main plot at 131 DAT, significantly higher shoot fresh weight was obtained by the inoculation with no P fertilizer in the fumigated main plot at this final sampling stage. These results indicate that the colonization of roots by introduced AM fungi is affected by the abundance of indigenous AM fungi and this interaction determines growth response of host plants under field conditions.

A knob bow fibula (Bügelknopffibel) of the Leutkirch type, which typologically belongs to the second half of the 4th and early 5th century CE, was excavated in 2018 in the Roman city of Augusta Raurica, present-day Kaiseraugst (AG, Switzerland). This was analyzed for the first time for its elemental composition by using the non-destructive technique of Muon Induced X-ray Emission (MIXE) in the continuous muon beam facility at the Paul Scherrer Institute (PSI). In the present work, the detection limit is 0.4 wt% with ∼ 1.5 hours of measurement time. The fibula was measured at six different positions, at a depth of 0.3–0.4 mm inside the material. The experimental results show that the fibula is made of bronze, containing the main elements copper (Cu), zinc (Zn), tin (Sn) and lead (Pb). The compositional similarities/differences between different parts of the fibula reveal that it was manufactured as two “workpieces”. One workpiece consists of the knob (13.0±0.6 wt% Pb), bow (11.9±0.4 wt% Pb) and foot (12.5 ± 0.9 wt% Pb). These show a higher Pb content, suggesting a cast bronze. The spiral (3.2 ± 0.2 wt% Pb), which is part of the other workpiece, has a comparatively lower Pb content, suggesting a forged bronze., Heritage Science, 11 (1), ISSN:2050-7445

Two adult patients with acute leukemia developed transplantation-associated microangiopathy (TAM) related to graft-versus-host disease (GVHD). Both patients were resistant to standard therapy for TAM and GVHD, which led to markedly elevated serum total bilirubin levels of 47.5 and 10.6 mg/dL, respectively. Transdermal isosorbide tape as a nitric oxide donor was applied to Patients 1 and 2 on post-transplantation days 60 and 66, respectively, which rapidly improved their jaundice after 1 day. This is the first report to describe the efficacy of transdermal isosorbide tape for adult patients with jaundice associated with TAM related to GVHD.

Catalytic hydrotreating of fatty acid is respected to produce bio-based chemicals especially oleochemicals that can be applied as a high valuable raw material or intermediate materials for industries. Low-cost Ni/LY char and limonite catalysts can compensate the expensively commercial catalysts. Palmitic acid (PA) was represented as reactant. Chemical compositions of liquid product were analyzed and presented in compound group, carbon number distribution and product selectivity. Catalyst characteristics and liquid product properties were also investigated. BET surface area, pore volume, and pore size of the prepared Ni/LY char catalyst were 308 m2/g, 0.188 cm3/g and 2.43 nm, respectively, and those of limonite catalyst were 95 m2/g, 0.3 cm3/g and 12.59 nm, respectively. Based on the initial 3 MPa H2 at 300 °C, the obtained oleochemicals depended on catalyst type, reaction time and solvent. In case of Ni/LY char catalyst, ester was found in yield of 58.94% that mainly contained with isopropyl palmitate up to 82% of ester, meanwhile product from limonite was principally distributed in alcohol group with 51.84% in which n-pentadecanol was the major compound with 37.05% yield. The products showed the oxygen removal in range of 19.11–65.15 mol% and HHVs were increased to 32.11–34.13 MJ/kg when compared with PA.

Sleep pressure, the driving force of the homeostatic sleep regulation, is accumulated during wakefulness and dissipated during sleep. Sleep deprivation (SD) has been used as a method to acutely increase animal’s sleep pressure for investigating the molecular changes under high sleep pressure. However, SD induces changes not only reflecting increased sleep pressure but also inevitable stresses and prolonged wake state itself. The Sik3Sleepy mutant mice (Sleepy) exhibit constitutively high sleep pressure despite sleeping longer, and have been useful as a model of increased sleep pressure. Here we conducted a cross-comparison of brain metabolomic profiles between SD versus ad lib slept mice, as well as Sleepy mutant versus littermate wild-type mice. Targeted metabolome analyses of whole brains quantified 203 metabolites in total, of which 43 metabolites showed significant changes in SD, whereas three did in Sleepy mutant mice. The large difference in the number of differential metabolites highlighted limitations of SD as methodology. The cross-comparison revealed that a decrease in betaine and an increase in imidazole dipeptides are associated with high sleep pressure in both models. These metabolites may be novel markers of sleep pressure at the whole-brain level. Furthermore, we found that intracerebroventricular injection of imidazole dipeptides increased subsequent NREM sleep time, suggesting the possibility that imidazole dipeptides may participate in the regulation of sleep in mice.

Cyanamide, is an inhibitor of aldehyde dehydrogenase, is widely used in patients with alcoholism. Although cyanamide is a causative drug for drug eruptions, mucosal adverse events of cyanamide have rarely been reported. Here, we report a case of cyanamide-induced oral lichenoid lesion. A 70-year-old man was admitted to the hospital because of the presence of oral lesions and difficulty in swallowing. He was taking cyanamide for the treatment of chronic alcoholism. The oral lichenoid lesions appeared one month after the initiation of cyanamide. The drug lymphocyte stimulation test for cyanamide was negative, while the patch test for cyanamide was positive. The symptoms improved 18 days after the discontinuation of cyanamide. A review of the literature has only 2 reports of cyanamide-induced lichenoid lesions with and/or without skin manifestations.

In this study, several nanometer-thick transition metal overlayers (M) were formed on an Fe–Cr–Al metal (SUS) foil by pulsed cathodic arc-plasma deposition. The thin-film materials prepared, exhibiting a full-coverage M overlayer (M/SUS), were applied as catalysts for NH3 oxidation in the presence of excess O2 (300 ppm NH3, 8% O2, and He balance). Under dry conditions (0% H2O in the gas feed), the observed NH3 oxidation activity decreased in the order of Ir > Pt > Co > Pd > Cu > Rh when the product selectivity was not taken into consideration. The activities of the materials composed of Co and Cu decreased significantly in the presence of 10% H2O, while those of the catalysts containing Pt and Ir remained nearly unchanged. Based on the kinetic analyses and X-ray photoelectron spectrometry experiments conducted, it was determined that the contrasting effect of H2O on the activity of M/SUS was related to the ease of oxidation of the non-precious metals studied. The resulting hydrophilic oxide surface was more susceptible to the competitive adsorption of H2O and thus inhibited the NH3 reaction than a metallic surface. The negative effect of H2O was evident by the decrease in the NH3 concentration in the gas feed. Notably, the metallic surface of the Pt overlayer was stable even under oxidizing reaction conditions; therefore, the oxidation of NH3 was less susceptible to the effects of high H2O concentrations.

X-ray photoelectron spectroscopy (XPS) is among the most powerful techniques to analyse structures of nitrogen-doped carbon materials. However, reported assignments of (1) graphitic nitrogen (N)/substitutional N, quaternary N (Q–N), or tertiary amine (T–N) and (2) pyrrolic N/secondary amine or T–N are questionable. Most reports assign peaks at ca. 401 eV as Q–N or graphitic N, whereas raw materials in most of those works contain neither counter anion nor halogen. Besides, the peak at ca. 400 eV has been assigned as pyrrolic N, but the presence of N–H is generally not confirmed. In this work, it was clarified that one of the reasons for the prevailing ambiguous assignments is the presence of N in heptagonal and pentagonal rings. The peaks at 400.1–401.2 eV were determined to be T–N, but not Q–N by analyzing graphitized polyimide (with the oxygen content of 0.01 at% or lower and the hydrogen content of 0 at%) using Raman spectroscopy, XPS, X-ray diffraction, total neutron scattering, elemental analysis, and molecular dynamics simulation. Besides, it was revealed that the peak at 400.1 eV originated from T–N on 5-membered rings or 7- and 5-membered rings, but not pyrrolic N because graphite including no hydrogen was used for analysis.

Extracellular vesicles (EVs) are biomarkers and mediators of intercellular communication. In biological samples, EVs are secreted by various types of cells. The proteomic identification of proteins expressed in EVs has potential to contribute to research and clinical applications, particularly for cancer. In this study, the proximity-labeling method-based proteomic approach was used for EV identification, labeling membrane components proximal to a given molecule on the EV membrane surface. Due to the small labeling range, proteins on the surface of the same EVs are likely to be labeled by selecting a given EV surface antigen. The protein group of cancer cell-secreted EV (cEV), which abundantly expresses a close homologue of L1 (CHL1), was examined using a model mouse for lung cancer (LC). cEV-expressed proteins were identified by proteomic analysis of enzyme-mediated activation of radical sources by comparing serum EVs from wild-type and LC mice. SLC4A1 was found to be co-expressed in CHL1-expressing EVs, highlighting EVs expressing both CHL1 and SLC4A1 as candidates for cEVs. Serum EVs expressing both CHL1 and caspase 14 were significantly elevated in LC patients compared with healthy individuals. Thus, the combination of proximity labeling and proteomic analysis allows for effective EV identification.

Although electrolyte abnormalities are related to worse clinical outcomes in patients with acute myocardial infarction (AMI), little is known about the association between admission serum magnesium level and adverse events in AMI patients complicated by out-of-hospital cardiac arrest presenting with malignant ventricular arrhythmias (OHCA-MVA). We investigated the prognostic value of serum magnesium level on admission in these patients.We retrospectively analyzed the data of 165 consecutive reperfused AMI patients complicated with OHCA-MVA between April 2007 and February 2020 in our university hospital. Serum magnesium concentration was measured on admission. The primary outcome was in-hospital death.Fifty-four patients (33%) died during hospitalization. Higher serum magnesium level was significantly related to in-hospital death (FineGray's test; p 0.001). In multivariable logistic regression analyses, serum magnesium level on admission was independently associated with in-hospital death (hazard ratio 2.68, 95% confidence interval 1.24-5.80) even after adjustment for covariates. Furthermore, the incidences of cardiogenic shock necessitating an intra-aortic balloon pump (p = 0.005) or extracorporeal membrane oxygenation (p 0.001), tracheal intubation (p 0.001) and persistent vegetative state (p = 0.002) were significantly higher in patients with higher serum magnesium level than in those with lower serum magnesium level.In reperfused AMI patients complicated by OHCA-MVA, admission serum magnesium level might be a potential surrogate marker for predicting in-hospital death.

We herein report two cases of locally advanced unresectable hepatocellular carcinoma (u-HCC) that were resected after achieving a radiological complete response to initially administered lenvatinib followed by transcatheter arterial chemoembolization (LEN-TACE sequential therapy). A 78-year-old woman and an 80-year-old man with HCC of Barcelona Clinic Liver Cancer classification stage C were treated for 15 and 14 months with lenvatinib, respectively. Both patients were subsequently treated with TACE, resulting in complete remission on imaging. The α-fetoprotein level in the woman and man decreased markedly from 9370 ng/ml to 46 ng/ml and from 6380 ng/ml to 3 ng/ml, respectively, leading to hepatectomy. A histopathological examination showed coagulative necrosis of the entire HCC in one case, while the other showed a small population of viable HCC cells. The results showed that LEN-TACE sequential therapy has a synergic effect and could be a promising option for locally advanced u-HCC.

We previously found that a single dose of B-type procyanidin mixture increase in skeletal muscle blood flow (BF). We compared BF changes following administration of (-)-epicatechin (EC, monomer) and the B-type procyanidins procyanidin B2 (B2, dimer), procyanidin C1 (C1, trimer), and cinnamtannin A2 (A2, tetramer). Each chemical was administered orally to rats, followed by BF measurement in cremaster arteriole for 60 min. About 10 and 100 µg/kg of B2 and C1 elicited BF increase, the effect was potent at 100 µg/kg. BF also increased significantly after administration of 10 µg/kg A2, but not with the administration at 100 µg/kg. EC yielded no BF changes. Co-treatment with the nonselective adrenaline blocker carvedilol attenuated the BF increase seen with 10 µg/kg A2 treatment. This outcome suggested the involvement of sympathetic nerve activation in the BF increase by this dose of A2. Co-treatment of 100 µg/kg A2 with the α2 blocker yohimbine exhibited an increase of BF significantly. The α2 adrenaline receptor in the vasomotor centre is an inhibitory receptor and it regulates hemodynamics. This result suggested that high doses of A2 did not alter BF because of activating the α2 adrenergic receptor. Phosphorylation of aortic endothelial nitric oxide synthase (eNOS) increased with 10 µg/kg A2 alone or co-treatment with 100 µg/kg A2 and yohimbine, but not with co-treatment of 10 µg/kg A2 and carvedilol or 100 µg/kg A2 alone. These results imply that A2 does not directly activate eNOS, but that shear stress from the increased BF might be associated with eNOS phosphorylation.

We herein report a 56-year-old woman who developed allergic bronchopulmonary aspergillosis (ABPA) possibly due to fungal exposure after disastrous heavy rainfall in Western Japan in 2018. She was diagnosed with ABPA complicated with asthma, increased peripheral blood eosinophil count, elevation of specific immunoglobulin E for Aspergillus fumigatus, positive Aspergillus fumigatus precipitation antibody reaction test results, and notable chest computed tomography findings. After treatment with benralizumab, her symptoms, peripheral blood eosinophil count, radiological findings, and respiratory function dramatically improved. The administration of benralizumab appears to be an effective treatment strategy for ABPA.

Direct-acting antiviral (DAA) therapy carries a potential risk of inducing hepatitis B virus (HBV) reactivation. However, the HBV kinetics during and after DAA therapy in patients co-infected with hepatitis C virus (HCV) and HBV remain unknown. We retrospectively evaluated the HBV kinetics during and after sofosbuvir/ribavirin therapy in four HBV inactive carriers co-infected with HCV. HCV was eradicated in all patients. Changes in HBV-DNA levels during treatment differed among patients. The hepatitis B surface antigen (HBsAg) levels uniformly decreased (mean -0.530 logIU/mL) by the end of treatment and returned to near the baseline in all patients. Sofosbuvir/ribavirin therapy thus demonstrated a suppressive effect on HBsAg.

Colloidal metal nanoparticles were examined for reductive amination of phenol by ammonia under mild reaction conditions. The results showed that Rh-PVP was the most active catalyst for reductive am...

The assembly of donor–acceptor molecules via charge transfer (CT) interactions gives rise to highly ordered nanomaterials with appealing electronic properties. Here, we present the synthesis and bulk co-assembly of pyrene (Pyr) and naphthalenediimide (NDI) functionalized oligodimethylsiloxanes (oDMS) of discrete length. We tune the donor–acceptor interactions by connecting the pyrene and NDI to the same oligomer, forming a heterotelechelic block molecule (NDI-oDMSPyr), and to two separate oligomers, giving Pyr and NDI homotelechelic block molecules (Pyr-oDMS and NDI-oDMS). Liquid crystalline materials are obtained for binary mixtures of Pyr-oDMS and NDI-oDMS, while crystallization of the CT dimers occurred for the heterotelechelic NDI-oDMS-Pyr block molecule. The synergy between crystallization and phase-segregation coupled with the discrete length of the oDMS units allows for perfect order and sharp interfaces between the insulating siloxane and CT layers composed of crystalline CT dimers. We were able to tune the lamellar domain spacing and donor–acceptor CT interactions by applying pressures up to 6 GPa on the material, making the system promising for soft-material nanotechnologies. These results demonstrate the importance of the molecular design to tune the CT interactions and stability of a CT material., A robust, soft material held together by charge transfer interactions is developed. The nanostructure dimensions and material properties can be tuned by molecular design or pressure.

Silver nanoparticles (AgNPs) are practically valuable in biological applications. However, no steady PEGylation has been established, which is essential for internal use in humans or animals. In this study, cyclic PEG (c-PEG) without any chemical inhomogeneity is physisorbed onto AgNPs to successfully PEGylate and drastically enhance the dispersion stability against physiological conditions, white light, and high temperature. In contrast, linear HO-PEG-OH and MeO-PEG-OMe do not confer stability to AgNPs, and HS-PEG-OMe, which is often used for gold nanoparticles, sulfidates the surface to considerably degrade the properties. TEM shows an essentially intact nanostructure of c-PEG-physisorbed AgNPs even after heating at 95 degrees C, while complete disturbance is observed for other AgNPs. Molecular weight- and concentration-dependent stabilization by c-PEG is investigated, and DLS and zeta-potential measurements prove the formation of a c-PEG layer on the surface of AgNPs. Furthermore, c-PEG-physisorbed AgNPs exhibit persistent antimicrobial activity and cytotoxicity.

In this work, we propose lateral voltage as a new input for use in artificial lipid bilayer systems in addition to the commonly used transmembrane voltage. To apply a lateral voltage to bilayer lipid membranes, we fabricated electrode-equipped silicon and Teflon chips. The Si chips could be used for photodetector devices based on fullerene-doped lipid bilayers, and the Teflon chips were used in a study of the ion channel functions in the lipid bilayer. The findings indicate that the lateral voltage effectively regulates the transmembrane current, in both ion-channel-incorporated and fullerene-incorporated lipid bilayer systems, suggesting that the lateral voltage is a practicable and useful additional input for use in lipid bilayer systems.

Carrier extraction in mixed tin–lead perovskite solar cells is improved by modifying the top and bottom perovskite surfaces with ethylenediammonium diiodide and glycine hydrochloride, respectively. Trap densities in perovskite layers are reduced as a result of surface passivation effects and an increase in film crystallinity. In addition, the oriented aggregation of the ethylenediammonium and glycinium cations at the charge collection interfaces results in the formation of surface dipoles, which facilitate charge extraction. As a result, the treated mixed tin–lead perovskite solar cells showed improved performance, with a fill factor of 0.82 and a power conversion efficiency of up to 23.6%. The unencapsulated device also shows improved stability under AM1.5 G, retaining over 80% of the initial efficiency after 200 h continuous operation in an inert atmosphere. Our strategy is also successfully applied to centimeter-scale devices, with efficiencies of up to 21.0%., スズを含むペロブスカイト太陽電池：23.6%の世界最高効率を達成 --ペロブスカイト薄膜の上下表面構造修飾法を開発--. 京都大学プレスリリース. 2022-04-13.

Significance: Magnetic resonance imaging (MRI) with hyperpolarized (HP) 13C-labeled redox-sensitive metabolic tracers can provide noninvasive functional imaging biomarkers, reflecting tissue redox state, oxidative stress, and inflammation, among others. The capability to use endogenous metabolites as 13C-enriched imaging tracers without structural modification makes HP 13C MRI a promising tool to evaluate redox state in patients with various diseases. Recent Advances: Recent studies have demonstrated the feasibility of in vivo metabolic imaging of 13C-labeled tracers polarized by parahydrogen-induced polarization techniques, which offer a cost-effective alternative to the more widely used dissolution dynamic nuclear polarization-based hyperpolarizers. Critical Issues: Although the fluxes of many metabolic pathways reflect the change in tissue redox state, they are not functionally specific. In the present review, we summarize recent challenges in the development of specific 13C metabolic tracers for biomarkers of redox state, including that for detecting reactive oxygen species. Future Directions: Applications of HP 13C metabolic MRI to evaluate redox state have only just begun to be investigated. The possibility to gain a comprehensive understanding of the correlations between tissue redox potential and metabolism under different pathological conditions by using HP 13C MRI is promoting its interest in the clinical arena, along with its noninvasive biomarkers to evaluate the extent of disease and treatment response.

Electronic structure of organic semiconductor that is governed by the packing structure in the solid state is critically important for the transport properties of organic-semiconductor solid. Dinaphtho[2,3-b:2′,3′-f]thieno[3,2-b]thiophenes (DNTT), which has been utilized as an active semiconducting material in high-performance organic field-effect transistors (OFETs), crystalized into a herringbone packing structure that affords the two-dimensional (2D) electronic structure. Here we have investigated effects of substituents on the packing structure of a series of DNTT derivatives modified with a (trialkylsilyl)ethynyl substituents. The packing structures of the derivatives with small (trialkylsilyl)ethynyl substituents, such as (trimethylsilyl)ethynyl (TMSE) (1) and (triethylsilyl)ethynyl (TESE) groups (2), were revealed to be the herringbone packing, whereas (triisopropylsilyl)ethynyl (TIPSE)-substituted DNTT (3) crystalized into a sandwich herringbone structure, in which face-to-face dimers of molecules are packed into a herringbone array. In-depth analyses of the packing structures by means of the functional-group symmetry-adapted perturbation theory (F-SAPT) calculations showed that the size of the TESE groups is critical to determine the packing structure; intermolecular interaction between the sterically demanding TIPSE groups does not allow 3 to crystalize into the herringbone structure that is favorable for the most of DNTT derivatives including 1 and 2. Although the sandwich herringbone structure has not been regarded as a potential one for efficient carrier transport in the solid state, the OFETs based on 1−3 showed comparable high mobility of 0.34 to 1.1 cm2 V−1 s−1, indicating that the sandwich herringbone structure is not necessarily quite unsuitable for carrier transport, which was also endorsed by the transfer integrals calculated based on the packing structure elucidated by the single crystal X-ray analysis. These results imply that versatile modifications on the molecular and packing structures can be applied to the DNTT core for the development of superior organic semiconductors.

The authors have proposed a new combustion process called the Plume Ignition Combustion Concept (PCC), in which with an optimal combination of hydrogen injection timing and controlled jet geometry, the plume of the hydrogen jet is spark-ignited to accomplish combustion of a rich mixture. This combustion process markedly improves thermal efficiency by reducing cooling loss, which is essential for increasing thermal efficiency in a hydrogen engine while maintaining high power. In order to improve thermal efficiency and reduce NOx formation further, PCC was applied to a lean-burn regime to burn a leaner mixture globally. In this study, the effect of supercharging which was applied to recover the reduced output power due to the leaner mixture on improving thermal efficiency was confirmed along with clarifying the cause.

Two-dimensional layered materials have been investigated for sensor applications over the last decade due to their very high specific surface area and excellent electrical characteristics. Although grain boundaries are inevitably present in polycrystalline-layered materials used for real applications, few studies have investigated their effects on sensing properties. In this study, we demonstrate the growth of two distinct MoS2 films that differ in grain size by means of chemical vapor deposition (CVD) and thermal vapor sulfurization (TVS) methods. Transistor-based sensors are fabricated using these films, and their NO2 sensing properties are evaluated. The adsorption behavior of NO2 on MoS2 is considered in terms of the Langmuir isotherm, and the experimental results can be well fitted by the equation. The CVD-grown film exhibits electrical properties 1–2 orders of magnitude superior to those of the TVS-grown one, which is attributed to the large grain size of the CVD-grown film. In contrast, the sensitivity to NO2 is unexpectedly found to be higher in the TVS-grown film and is of the same order of a previously reported record value. Transmission electron microscopy observations suggest that the TVS-grown film consists of multiple rotationally oriented grains that are connected by mirror twin grain boundaries. Theoretical calculation results reveal that the adsorption of NO2 on the grain boundary that we modeled is equal to that on the ideal basal plane surface of MoS2. In addition, the porous structure in the TVS-grown film may also contribute to enhancing the sensor response to NO2. This study suggests that a highly sensitive MoS2 sensor can also be fabricated by using a polycrystalline film with small grain size, which can possibly be applied to other two-dimensional materials.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by selective loss of motor neurons. We have previously shown that autophagosome-like vesicular structures are progressively accumulated in the spinal axons of an ALS mouse model, overexpressing human Cu/Zn superoxide dismutase (SOD1) mutant, prior to the onset of motor symptoms. This suggests that axonal transport perturbation can be an early sign of neuronal dysfunction. However, the exact causal relationship between axonal transport deficits and neurodegeneration is not fully understood. To clarify whether axonal transport of organelles even in neurons at early developmental stages was affected by overexpression of mutant SOD1, we conducted a microfluidic device-based high-throughput quantitative analysis of the axonal transport of acidic vesicles and mitochondria in primary cultured cortical neurons established from SOD1H46R transgenic mice. Compared to wild-type (WT), a significantly increased number of motile acidic vesicles, i.e., autophagosomes and/or late-endosomes, was observed in the axons of SOD1H46R neurons. By contrast, mitochondria moving along the axons were significantly decreased in SOD1H46R compared to WT. Since such phenotypes, where the axonal transport of these organelles is differently affected by mutant SOD1 expression, emerge before axonal degeneration, axonal transport deficits could dysregulate axon homeostasis, thereby ultimately accelerating neurodegeneration.

In order to establish carbon capture, utilization, and storage (CCUS) technology, we focused on a system consisting of two different biocatalysts (formate dehydrogenase from Candida boidinii; CbFDH and carbonic anhydrase from bovine erythrocytes; CA). CA catalyses the interconversion between CO2/water and dissociated bicarbonate ions/protons. CbFDH is a NAD+-dependent dehydrogenase that catalyzes CO2 reduction to formate by using the NAD+/NADH redox couple. The construction of a bienzymatic system consisting of CA and CbFDH (CA/CbFDH system) for a CCUS system was attempted. At 150 or 200 μM CA in the sample solution and a controlled pH of 6.3–6.5 by CO2 bubbling, due to the promotion of the conversion of CO2 to bicarbonate, the reaction rate for CbFDH-catalyzed CO2 reduction to formate decreased to about 50% as compared with that in the absence of CA. In the higher pH region (>9.5), despite the low CO2 concentration in this region, in contrast, it was found that the addition of CA promoted the reduction of CO2 catalyzed by CbFDH to formate to about 7 times higher than that under the conditions without CA. This shows that a CCUS system was constructed in which the conversion of bicarbonate to CO2 using CA and the reduction of CO2 to formate using CbFDH were coordinated.

The photoreduction of CO2 catalyzed by [fac-Re(dmbpy)(CO)3Cl] was precisely investigated through operando measurements of X-ray absorption fine structure spectroscopy (XAFS) and laser-flash FT-IR transient spectroscopy. In the early stage of the photoreaction, Re0-species assigned as penta-coordinated complex, [Re0(dmbpy)(CO)3], appeared and a delayed rise of ReII-species, [ReII(dmbpy)(CO)3CO2] (3) / [ReII(dmbpy)(CO)3COOH]+ (3’), were observed in XAFS measurements. The valence state of Re-center in the catalytic cycle changed as ReI → Re0 → ReII to be a clear evidence of an oxidative addition of CO2 to the Re0 center. In the laser-flash induced FT-IR measurements, a rise and decay of 3 followed by a delayed rise and decay of 3’ was observed. The second electron transfer from the carbon radical of TEA to 3’ induced the formation of [ReI(dmbpy)(CO)4]+ through [ReI(dmbpy)COOH]. The rate determining step of the catalytic cycle was revealed to be the protonation process of forming 3’ from 3.

Background Efficient cell-free protein expression from linear DNA templates has remained a challenge primarily due to template degradation. In addition, the yields of transcription in cell-free systems lag behind transcriptional efficiency of live cells. Most commonly used in vitro translation systems utilize T7 RNA polymerase, which is also the enzyme included in many commercial kits. Results Here we present characterization of a variant of T7 RNA polymerase promoter that acts to significantly increase the yields of gene expression within in vitro systems. We have demonstrated that T7Max increases the yield of translation in many types of commonly used in vitro protein expression systems. We also demonstrated increased protein expression yields from linear templates, allowing the use of T7Max driven expression from linear templates. Conclusions The modified promoter, termed T7Max, recruits standard T7 RNA polymerase, so no protein engineering is needed to take advantage of this method. This technique could be used with any T7 RNA polymerase- based in vitro protein expression system.

Background Silver is a transition metal that is known to be less toxic than platinum. However, only few studies have reported the anticancer effects of some silver complexes and their possibility as an alternative to platinum complex. This study investigated the anticancer effects of the silver thiosulfate complex (STS), [Ag(S2O3)2]3−, consisting of silver and sodium thiosulfate. Methods In vitro cytotoxic activity of STS was investigated comparatively in human cancer cell lines (K562 and MCF-7) and normal human cells (mesenchymal stem cells and mammary epithelial cells). For its anticancer effects, cell cycle, mode of cell death, morphological changes, and accumulation of intracellular ROS and GSH were evaluated in MCF-7 to provide mechanistic insights. Results STS showed a concentration-dependent cytotoxicity in MCF-7 cell, which was abolished by pretreatment with N-acetylcysteine, suggesting ROS accumulation by STS. Moreover, STS caused cell cycle arrest at the G1 phase, decrease in the GSH levels, and morphological changes in MCF-7. Direct measurement of ROS demonstrated the elevation of intracellular ROS accumulation in cancer cells treated with STS; however, neither cytotoxicity nor ROS accumulation was observed in normal human cells. Conclusion The results obtained here are the first evidence to show that STS exhibited an anticancer activity through ROS-induced mechanisms, and that its cytotoxicity is highly selective to cancer cells. The results of the present study warrant further investigation on the detailed mechanism of STS actions, as well as its in vivo effectiveness and safety for clinical application.

Objectives Our previous investigations showed that tissue stem cells in the maculae flavae (a stem cell niche) form colonies in vivo like stem cells in vitro. However, the roles of colony‐forming cells in the maculae flavae in vivo have not yet been determined. This study investigated the metabolism of the colony‐forming tissue stem cells in the maculae flavae of the human adult vocal fold. Study design Histologic analysis of the human vocal folds. Methods Three normal human adult vocal folds were investigated under transmission electron microscopy and light microscopy including immunohistochemistry. Results Mitochondrial cristae of the colony‐forming cells in the maculae flavae were sparse. Hence, the microstructural features of the mitochondria suggested that their metabolic activity and oxidative phosphorylation were low. Colony‐forming cells strongly expressed glucose transporter‐1 and glycolytic enzymes (hexokinase II, glyceraldehyde‐3‐phosphate dehydrogenase and lactate dehydrogenase A). The colony‐forming cells did not express phosphofructokinase‐1 but did express glucose‐6‐phosphate dehydrogenase indicating the cells relied more on the pentose phosphate pathway. Since the colony‐forming cells expressed lactate dehydrogenase A, cells seemed to rely more on anaerobic glycolysis in an anaerobic microenvironment. Conclusions The present study is consistent with the hypothesis that the colony‐forming tissue stem cells in the maculae flavae of the human adult vocal fold seemed to rely more on anaerobic glycolysis using the pentose phosphate pathway for energy supply in vivo. Microstructural features of the mitochondria and expressed glycolytic enzymes of the colony‐forming cells in the maculae flavae suggested that the oxidative phosphorylation activity was low. In an anaerobic microenvironment in vivo, there is likely a complex cross‐talk regarding the metabolism between the colony‐forming aggregated cells along the adhesion machinery and chemical signaling pathways, which reduces toxic oxygen species and is favorable to maintaining the stemness and undifferentiated states of the tissue stem cells. Level of Evidence NA.

Periodic fever syndromes are heterogeneous diseases. Familial Mediterranean fever (FMF) is one of the hereditary periodic fever diseases caused by a Mediterranean fever (MEFV) gene abnormality. FMF can be categorized as typical or atypical, based on clinical findings and genetic screening. Atypical FMF has a wide variation of clinical findings and disease-causing mutations of MEFV. Therefore, it is sometimes difficult to diagnose an unknown fever as FMF. To date, a large number of various typical and atypical FMF cases have been reported in Japan. Here, we describe a Japanese boy with heterozygous MEFV p.Ser503Cys exon 5 variant who developed periodic fever. He was treated with colchicine; a complete eradication of his fever and various accompanying symptoms have been subsequently achieved for more than a year. Given that there have been a few reports about patients with this variant, little is known about the genetic and phenotypic role of heterozygous MEFV p.Ser503Cys exon 5 variant. It is therefore imperative to consider atypical FMF as a differential diagnosis when a periodic fever is encountered. Furthermore, we suggest that it is worthwhile to integrate MEFV gene analysis with the potential effects of colchicine treatment in patients with periodic fever.