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Small-colony variants (SCVs) of bacteria are subpopulations with a small colony size, low growth rate, and atypical colony morphology. The purpose of this study was to comprehensively elucidate the characteristics and underlying mechanism of the development of a glutamine-dependent SCV of E. coli, GU-92The GU-92The colony of the GU-92To the best of our knowledge, this is the first clinical isolation of a glutamine-dependent E. coli SCV from a patient blood culture. Our data showed that glnA was important for the growth of E. coli in Mueller-Hinton II medium, which also required the presence of glutamine when performing antimicrobial susceptibility testing for glutamine-dependent SCV strains.

Objective The blowing time ratio, which is the ratio of the blowing time when the nostrils are open and closed, is significantly correlated with velopharyngeal pressure, not only during speech but also during swallowing. This study aimed to further evaluate the usefulness of the blowing time ratio as a screening tool to evaluate the swallowing pressure of patients treated for oral and oropharyngeal cancers using high-resolution manometery (HRM). Methods Ten patients treated for oral or oropharyngeal cancer were recruited for this study. Swallowing pressures at the velopharynx, oropharynx , and upper esophageal sphincter (UES) were measured using HRM. Their correlations with the blowing time ratio were analyzed. Results The blowing time ratio was significantly correlated with the swallowing pressures of the oropharynx (CC = 0.815, p = 0.004) and the velopharynx (CC = 0.657, p = 0.039), but not of the UES. Conclusions The present results further support our previous finding that the blowing time ratio is a useful screening tool to evaluate velopharyngeal and oropharyngeal swallowing pressures in patients treated for oral and oropharyngeal cancer.

The transition from smectite to illite at around the depth with temperature of ~150 °C has long been hypothesized as one of controlling factors of the updip limit depth of the seismogenic zone of subduction zones. Although illite has a higher friction coefficient than smectite, previous friction experiments have little reported that the smectite-illite transition accompanies the transition from velocity strengthening (not seismogenic) to velocity weakening (potentially seismogenic). In this study, we simulated in-situ temperature-pressure-mineral conditions along the shallow plate boundary in the Nankai Trough, and conducted friction experiments to further constrain the role of smectite-illite transition in seismogenesis in subduction zones. We found that friction coefficient of the simulated sediment increased with the progress of illitization and followed the Reuss average of friction coefficients of the mineral phases. The obtained friction coefficients and the Coulomb wedge model inferred that the pore pressure conditions around the plate boundary may be over-pressured but not as high as lithostatic pressure. Higher friction coefficients of sediment due to diagenetic processes will be required to sustain the nearly lithostatic pore pressure along the plate boundary. The velocity dependence of friction coefficient (a−b) was always positive except under the velocity conditions lower than ~10 μm/s at 171 °C. Therefore, the shallow slow earthquakes beneath the outer prism cannot be explained only by the frictional instability of unconsolidated sediment. Since the smectite-illite transition mostly completes at ~30 km landward from the trough axis, the transition from velocity strengthening to velocity weakening observed at 171 °C is caused by temperature-dependent frictional behavior of illite-rich material. Hence the updip limit depth of the seismogenic zone of subduction zones would be mainly controlled by frictional properties of illite-rich material.

In the present study, we evaluated the effects of kaempferol on bone marrow-derived mast cells (BMMCs). Kaempferol treatment significantly and dose-dependently inhibited IgE-induced degranulation, and cytokine production of BMMCs under the condition that cell viability was maintained. Kaempferol downregulated the surface expression levels of FcεRI on BMMCs, but the mRNA levels of FcεRIα, β, and γ-chains were not changed by kaempferol treatment. Furthermore, the kaempferol-mediated downregulation of surface FcεRI on BMMCs was still observed when protein synthesis or protein transporter was inhibited. We also found that kaempferol inhibited both LPS- and IL-33-induced IL-6 production from BMMCs, without affecting the expression levels of their receptors, TLR4 and ST2. Although kaempferol treatment increased the protein amount of NF-E2-related factor 2 (NRF2)—a master transcription factor of antioxidant stress—in BMMCs, the inhibition of NRF2 did not alter the suppressive effect of kaempferol on degranulation. Finally, we found that kaempferol treatment increased the levels of mRNA and protein of a phosphatase SHIP1 in BMMCs. The kaempferol-induced upregulation of SHIP1 was also observed in peritoneal MCs. The knockdown of SHIP1 by siRNA significantly enhanced IgE-induced degranulation of BMMCs. A Western blotting analysis showed that IgE-induced phosphorylation of PLCγ was suppressed in kaempferol-treated BMMCs. These results indicate that kaempferol inhibited the IgE-induced activation of BMMCs by downregulating FcεRI and upregulating SHIP1, and the SHIP1 increase is involved in the suppression of various signaling-mediated stimulations of BMMCs, such as those associated with TLR4 and ST2.

Vertical partial laryngectomy is a well-established surgical procedure for early glottic cancers with acceptable functional and oncological outcomes. However, on a long-term basis, aspiration might be a serious problem with aging. Here we presented two cases of refractory aspiration pneumonia after vertical laryngectomy. Case 1: A 76-year old gentleman with a past history of malignant lymphoma treated by chemotherapy and radiotherapy had glottic cancer, which was treated by repeated vertical partial laryngectomies. Although glottic caner had been well controlled, he started to suffer from refractory aspiration pneumonia. Since his cervical skin was very thin and hard and his general condition was poor, we employed modified Kano's method for glottic closure. Case 2: A 87-year old Japanese male had a past history of glottic cancer treated by radiotherapy and vertical partial laryngectomy. He was repeatedly hospitalized for severe aspiration pneumonia. At the age of 87, he had second primary oropharyngeal cancer. Kano's method was simultaneously performed at the time of resection of oropharyngeal cancer. Postoperative courses were uneventful without sign of leakage in both cases. The patients started oral intake 2 weeks after the surgery. They have been alive without aspiration pneumonia and takes normal diet.

Nucleation of earthquake slip at the plate boundary fault (décollement) in subduction zones has been widely linked to the frictional properties of subducting sedimentary facies. However, recent seismological and geological observations suggest that the décollement develops in the subducting oceanic crust in the depth range of the seismogenic zone, at least in some cases. To understand the frictional properties of oceanic crustal material and their influence on seismogenesis, we performed hydrothermal friction experiments on simulated fault gouges of altered basalt, at temperatures of 100–550°C. The friction coefficient (μ) lies around 0.6 at most temperature conditions but a low μ down to 0.3 was observed at the highest temperature and lowest velocity condition. The velocity dependence of μ, (a−b), changes with increasing temperature from positive to negative at ∼100°C and from negative to positive at ∼450°C. Compared to gouges derived from sedimentary facies, the altered basalt gouge showed potentially unstable velocity weakening over a wider temperature range. Microstructural observations and microphysical interpretation infer that competition between dilatant granular flow and viscous compaction through pressure-solution creep of albite contributed to the observed transition in (a−b). Alteration of oceanic crust during subduction produces fine grains of albite and chlorite through interactions with interstitial water, leading to reduction in its frictional strength and an increase in its seismogenic potential. Therefore, shear deformation possibly localizes within the altered oceanic crust leading to a larger potential for the nucleation of a megathrust earthquake in the depth range of the seismogenic zone.

Welcome progress has been made towards realising commitments made by international donors and host country governments to expand economic opportunities for Syrian refugees and host communities in neighbouring countries. However targets and commitments also bring new challenges, and evidence must underpin new policies.

In this study, a calcium/carbon composite (Ca/C) was prepared from porous Ca0 by the water vapor swelling method; its pores were filled with tar-derived carbonaceous material to produce high-strength and highly reactive coke. The properties of coke prepared by blending the Ca/C composite and caking-coal were then investigated. The mesopores in the swelling Ca disappeared and the crushing strength was developed by filling tar-derived carbonaceous material into the porous Ca. Thus, a Ca/C composite could be produced by the abovementioned method, wherein the tar-derived carbonaceous material and Ca species were in close proximity. When the Ca/C composite was blended into the caking-coal, the strength of the coke obtained increased by up to 50% of Ca/C blending, which made it possible to produce high-strength coke. On examining the C structure of the prepared coke by X-ray diffraction, that of the original coke was found to be almost unchanged by adding the Ca/C composite. Conversely, the Ca/C blended-coke showed higher CO2 gasification reactivity than the original coke prepared from caking-coal. Based on the CO2 gasification reactivity test of the demineralized coke, it was clear that an increase in the gasification reactivity of the Ca/C blended-coke depended upon the catalytic effect of Ca. Thus, this method helped produce high-strength and highly reactive coke.

The purpose of this study is to investigate the extent to which college students have global awareness and competence and to examine the effects of global education on their attitudes toward global citizenship. The subjects were 26 students who wanted to transfer to a four-year college. They took a questionnaire that was used in PISA （Programme for International Student Assessment） 2018 Global Competence Survey before and after the class practice. Moreover, the same survey was conducted again almost six months later to see the relationship between the number of lessons and the growth of awareness and competence. All data were examined statistically. In conclusion, students before taking global education lessons thought they did not possess enough knowledge, self-efficacy, and a feeling of belonging towards a global community, while they had strong interests in knowing global and cultural issues and positive attitudes toward respecting multiculturalism. Moreover, global education increased not only their sense of being in a global community significantly but also identifying with their nation and region, regardless of the number of lessons. The results showed that global education was effective for improving a sense of global citizenship and had a positive ripple effect, especially on student attitudes, which accordingly may enhance learning outcomes compared with another method.

Idiopathic pulmonary hemosiderosis is characterized by repeated alveolar hemorrhaging. We herein report a 52-year-old Japanese woman who had shortness of breath, diffuse small nodules, thin-walled cysts, and bronchiolectasis. A surgical lung biopsy revealed peribronchial hemosiderosis, centrilobular emphysema, and fragile elastic fibers of the alveolar septa and small vessels. She ultimately underwent living-donor lung transplantation five years after the first visit.

A sensitive, useful and preliminary screening method was proposed to quantitate the containable cannabinoids most commonly included in mineral water and gummi candy products, specifically cannabidiol (CBD), cannabinol (CBN), 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCA), cannabigerol (CBG), and cannabidiolic acid (CBDA), using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) for quality evaluations. Based on the electrospray positive ion mode, the limit of detection and the limit of quantification values were 0.2 to 0.5 ng/mL and 0.8 and 2.0 ng/mL. Samples (0.5 g) were diluted by water/methanol (50/50), to which stable isotope internal standards were added; the recovery results appeared in range from 91.3 to 101.2%. This method was applied to evaluate CBD products (6 kinds) from the Japanese market. Our survey found obvious discrepancies between the labeling and the results were overserved in products. In addition, CBN, THCA, CBG, and CBDA were not detected in full-spectrum products that contained various cannabinoids that naturally occur in the cannabis plant. Thus, it is necessary to be able to verify the accurate concentration and impurity in various CBD products from the Japanese market as quickly as possible.

This report involved women’s junior college students who were interested in hospitality industry and tourism, and examined what they had learned from a one-day training program which enabled them to develop essential skills and mindsets for hospitality. The subjects were 27 students who were members of the Department of Liberal Arts for Career Development at Sakura no Seibo Junior College. They participated in a traditional Japanese way of hospitality program which aimed to provide them with the necessary soft skills and knowledge as potential young talent, and they were asked to describe two main subjects after the program; (i) What remained in the impression about the lecture? (ii) How do you want to apply what you have learnt about the program in your life? Quantitative text analysis was carried out by using KH Coder in order not to analyze with arbitrariness. Analysis was performed while confirming the original data using hierarchical clustering analysis. As a result, it was possible to confirm that subjects felt 5 main impressions which were related to interaction with others and nonverbal language. In addition, the program evoked a wide range of familiar situations that allowed them to practice what they have learnt from it.

In a clinical study of autologous cell–based therapy using dermal sheath cup (DSC) cells, the treatment of hair loss showed improvements. However, the outcomes were variable. Here, correlations between marker gene expression in DSC cells and treatment outcomes were assessed to predict therapeutic efficacy. Overall, 32 DSC cell lines were used to evaluate correlations between marker gene expression and treatment outcomes. Correlations between vascular pericyte and preadipocyte marker expression and treatment outcomes were inconsistent. As smooth muscle cell markers, MYOCD correlated negatively with treatment outcomes and SRF consistently demonstrated an inverse correlation. Additionally, CALD1 correlated negatively and ACTA2 correlated inversely with treatment outcomes. DSC cell lines were divided into good and moderate/poor responders to further investigate the correlations. SRF and CALD1 were lower in a good responder compared with a moderate responder. Next, DSC cells were differentiated toward dermal papilla cells. Dermal papilla markers SOX2 and LEF1 before differentiation had moderate positive and inverse correlations with the treatment outcome, respectively. SOX2 after differentiation more consistently demonstrated a positive correlation. Significant downregulation of smooth muscle–related genes was also observed after differentiation. These findings revealed putative markers for preclinical evaluation of DSC cells to improve hair loss.

Continental earthquakes often nucleate at the brittle-plastic transition zone in the upper crust. Since the strength of the crust reaches the maximum here, it is inferred that strain is localized, leading to seismic rupture. Fault rock deformation experiments under pressure-temperature conditions simulating the brittle-plastic transition are key to unravel the processes triggering continental earthquakes. We investigated the mechanical behavior and post-mortem microstructure of simulated quartz-feldspar gouges using a Griggs-type solid medium apparatus. The samples consist of mixtures of powdered quartz: albite = 50 : 50 (wt%), which were sheared under pressure-temperature conditions simulating depths of 7 to 30 km, realizing a geothermal gradient of 30 °C/km and a lithostatic pressure corresponding to a granitoid rock density of 2700 kg/m3. Specifically, experiments were carried out at temperatures ranging from 210 °C to 900 °C and confining pressures ranging from 185 MPa to 870 MPa. The bulk shear strain rate was sequentially stepped between ~10-3 and ~10-4 /s. After the experiments, each sample was analyzed using optical and scanning electron microscopy.Experimental results show a clear positive dependence of the shear strength on temperature and pressure up to 720 °C and 750 MPa, suggesting the dominance of brittle deformation. On the contrary, when the condition rises to 900 °C and 870 MPa, the strength dropped by about 550 MPa compared with that of at 720 °C and 750 MPa. This may imply that the plastic deformation gradually has taken over the deformation. Microstructural observation revealed elongated grains with their long axes intersecting with the direction of a Riedel-1(R1) shear plane (i.e., similar to a S-C fabric). Some grains were reduced in size to the nanometer range. Our observations suggest that shear strain was highly concentrated within fine-grained zones, which, we speculate, may lead to catastrophic rupture. Crack distributions illuminated by image analysis indicate that the formation mechanism of crack changes with temperature and pressure. At the lower temperature (~ 240 °C) and pressure (~ 212 MPa), cracks are short and oriented to various directions. However, as the temperature and pressure increase to 300 °C and 265 MPa, they become longer and the ratios of R1- and Y- shears increase. This implies that cracks coalesce in the kinematically favored orientations for slip, making it easy to cause a rapid seismic rupture. Since such microstructural changes occur at relatively low temperatures (below 720 °C), it is expected that the structures at higher temperatures (720 °C or higher) show predominance of the plastic deformation. Our results imply that the brittle-plastic transition gradually takes place at the microscopic scale, even within the range where the bulk mechanical behavior indicates brittle deformation.

Cannabidiol (CBD), a major non-psychoactive cannabinoid, has a lot of attention due to its potential relaxing properties and led the trend in commercial CBD aroma/oral hemp seed oil from the Japanese market. In this study, a routine assay for evaluating CBD oil samples was performed using LC coupled with tandem mass spectrometry (LC-MS/MS) and was used to apply the convertible tetrahydrocannabinol (THC) in acetic acid conditions. Based on the electrospray positive ion mode, the detection of cannabidiolic acid (CBDA; m/z 359 219), cannabigerolic acid (CBGA; m/z 361 343), cannabigerol (CBG; m/z 317 193), CBD (m/z 315 193), THC (m/z 315 193) and cannabinol (CBN; m/z 311 223) was performed by satisfying separation with high density of C

We report on the recommendation of the simple and versatility of methylated reference (MR) to improve applications in the single reference (SR)-LC based on relative molar sensitivity (RMS). Three curcuminoids (Curs) such as curcumin, demethoxycurcumin and bisdemethoxycurcumin in turmeric products were determined using authentic standards and methylated curcumin. In addition, high-speed countercurrent chromatography (HSCCC) purification is necessary to separate Curs for indicating the RMS. For HSCCC separation, a biphasic solvent system was used to obtain these fractions, which were then subjected to

trans-Fatty acids (TFAs) are unsaturated fatty acids that contain one or more carbon-carbon double bonds in trans configuration. Epidemiological evidence has linked TFA consumption with various disorders, including cardiovascular diseases. However, the underlying pathological mechanisms are largely unknown. Here, we show a novel toxic mechanism of TFAs triggered by DNA damage. We found that elaidic acid (EA) and linoelaidic acid, major TFAs produced during industrial food manufacturing (so-called as industrial TFAs), but not their corresponding cis isomers, facilitated apoptosis induced by doxorubicin. Consistently, EA enhanced UV-induced embryonic lethality in C. elegans worms. The pro-apoptotic action of EA was blocked by knocking down Sab, a c-Jun N-terminal kinase (JNK)-interacting protein localizing at mitochondrial outer membrane, which mediates mutual amplification of mitochondrial reactive oxygen species (ROS) generation and JNK activation. EA enhanced doxorubicin-induced mitochondrial ROS generation and JNK activation, both of which were suppressed by Sab knockdown and pharmacological inhibition of either mitochondrial ROS generation, JNK, or Src-homology 2 domain-containing protein tyrosine phosphatase 1 (SHP1) as a Sab-associated protein. These results demonstrate that in response to DNA damage, TFAs drive the mitochondrial JNK-Sab-ROS positive feedback loop and ultimately apoptosis, which may provide insight into the common pathogenetic mechanisms of diverse TFA-related disorders.

Silkworms are useful for evaluating substances that suppress postprandial hyperglycemia by oral administration. In this study, orally administered whey protein hydrolysate (WPH), obtained by enzymatic treatment of whey protein, suppressed sucrose-induced hyperglycemia in silkworms in a dose-dependent manner. WPH also inhibited glucose-induced hyperglycemia in silkworms. These findings suggest that WPH contains a bioactive peptide that inhibits glucose uptake from the intestinal tract and thereby suppresses sucrose-induced hyperglycemia.

Chlorite is abundant at hypocentral depths in subduction zones and is likely to play a key role in controlling megathrust slow slip and catastrophic rupture. However, no data exist on the frictional properties of chlorite(-rich) fault rocks under the hydrothermal conditions relevant for the subduction seismogenic zone. We report results from experiments conducted under such conditions, using chlorite powders prepared from single crystal clinochlore (Mg-chlorite), as well as limited experiments using a stack of single crystal sheets. Shear experiments were carried out at effective normal stresses (σn) of 100 to 400 MPa, pore fluid pressures (Pf) of 50 to 220 MPa, and at temperatures (T) of 22 to 600 °C, using stepped displacement rates (v) from 0.3 to 100 μm/s. The gouges are characterized by a coefficient of friction (μ) of 0.2–0.3 at T ≤ 400 °C and 0.3–0.4 at 500–600 °C, while (a-b) values showed positive values for nearly all conditions tested, except at 300 °C. Microstructures of gouges sheared at T ≤ 300 °C show evidence for widespread comminution, compared with a lower porosity at 600 °C. Experiments using a stack of single crystal sheets showed μ ≤ 0.008 at low displacements (

Purpose: We compare the cytotoxicity of anti-glaucoma prostaglandin ophthalmic solutions on human corneal epithelial cells and elucidate mechanisms of toxicity. Methods: Cell viability was examined using MTS assay, and morphological changes of the cells were observed. Induction of necrosis/apoptosis was measured by colorimetric caspase assay. The production of Reactive oxygen species (ROS) and release of cytokines were analyzed using 2', 7'-dichlorodihydrofluorescein diacetate and bead-based indirect immunofluorescent assay, respectively. Results: Xalatan, Lumigan 0.01%, and Lumigan 0.03% decreased cell viability and induced morphological changes. Xalatan and Lumigan 0.01% induced necrosis. Xalatan, Lumigan 0.01%, Lumigan 0.03%, and Taflotan stimulated ROS production. Travatan and Lumigan 0.03% increased concentrations of Interleukin (IL)-6 and IL-8 in culture media. Conclusions: Xalatan and Lumigan 0.01% ophthalmic solutions demonstrated potent cytotoxicity compared with Lumigan 0.03%, Travatan, Taflotan, and Taflotan UD. Taflotan UD, compared to Taflotan 0.0015%, induced less oxidative stress and apoptotic signalling. The cytotoxicity might be partly associated with benzalkonium chloride.

Receptor-interacting protein kinase 1 (RIPK1) is a key component of the tumor necrosis factor (TNF) receptor signaling complex that regulates both pro- and anti-apoptotic signaling. The reciprocal functions of RIPK1 in TNF signaling are determined by the state of the posttranslational modifications (PTMs) of RIPK1. However, the underlying mechanisms associated with the PTMs of RIPK1 are unclear. In this study, we found that RING finger protein 4 (RNF4), a RING finger E3 ubiquitin ligase, is required for the RIPK1 autophosphorylation and subsequent cell death. It has been reported that RNF4 negatively regulates TNF-α-induced activation of the nuclear factor-κB (NF-κB) through downregulation of transforming growth factor β-activated kinase 1 (TAK1) activity, indicating the possibility that RNF4-mediated TAK1 suppression results in enhanced sensitivity to cell death. However, interestingly, RNF4 was needed to induce RIPK1-mediated cell death even in the absence of TAK1, suggesting that RNF4 can promote RIPK1-mediated cell death without suppressing the TAK1 activity. Thus, these observations reveal the existence of a novel mechanism whereby RNF4 promotes the autophosphorylation of RIPK1, which provides a novel insight into the molecular basis for the PTMs of RIPK1.

This study describes the development of a new stable isotope labeling method by carbon-13 in bacteria culture (SILCB) for the analysis of residual antibiotics via liquid chromatography with tandem mass spectrometry (LC-MS/MS). Stable isotope dilution (SID) LC-MS/MS with QuEChERS was employed to determine avermectin, particularly avermectin B1a (AV-a) and B1b (AV-b), based on completely 13C-labeled internal standards (13C-ISs) obtained from the SILCB. Our SILCB was developed from an optimal inorganic medium using 13C6-glucose for Streptomyces avermitilis (14893 strain). A rough extract containing 13C-ISs was purified via high-speed countercurrent chromatography with a volatile two-phase solvent system composed of n-hexane/ethyl acetate/methanol/0.5% formic acid in water (7/3/5/5/, V/V). The purified 13C-ISs were evaluated to confirm the presence of completely 13C-labeled ions with m/z 938 > 326 and m/z 923 > 309 for AV-a and AV-b, respectively. The QuEChERS approach with the 13C-ISs procedure achieved acceptable recovery rates in beef meat samples of 99.5 - 100.0% (RSD < 2.0%, n = 6). For the analysis of residual antibiotics in foodstuffs by SID-LC-MS/MS and QuEChERS, the SILCB represents a significant improvement over previous methods suffering from cumbersome sample preparation and matrix effects.

Monitoring analysis of 14 per- and polyfluoroalkyl substances (PFAS), 9-chlorohexadecafluoro-3-oxanonane-1-sulfonate (F-53B) and dodecafluoro-3H-4,8-dioxanonanoate (ADONA) in bottled drinking water, tea and juice samples was performed using LC coupled with tandem mass spectrometry (LC-MS/MS) and solid-phase extraction (SPE). In the electrospray negative ion mode, the limit of detection and limit of quantification (LOQ) values were 0.1 to 0.8 ng/mL and 0.2 to 1.6 ng/mL, respectively. The calibration curves were linear from LOQ to 50 ng/mL (r2 > 0.999). The SPE procedure (Presep PFC-II) was utilized for sample preparation and recovery rates for three standards (35, 70 and 140 ng/L) were 80.4-118.8% with relative standard deviation (RSD) ≤ 0.6%. Using the developed method, various samples (n = 54) from Japanese markets were investigated for PFAS and F-53B contamination, and values below the LOQ were observed. It is concluded that for monitoring products in the Japanese market, our method represents a significant improvement over complex techniques for the quantification of PFAS and related compounds from various foods.

trans-Fatty acids (TFAs) are food-derived fatty acids associated with various diseases including cardiovascular diseases. However, the underlying etiology is poorly understood. Here, we show a pro-apoptotic mechanism of TFAs such as elaidic acid (EA), in response to DNA interstrand crosslinks (ICLs) induced by cisplatin (CDDP). We previously reported that TFAs promote apoptosis induced by doxorubicin (Dox), a double strand break (DSB)-inducing agent, via a non-canonical apoptotic pathway independent of tumor suppressor p53 and apoptosis signal-regulating kinase (ASK1), a reactive oxygen species (ROS)-responsive kinase. However, here we found that in the case of CDDP-induced apoptosis, EA-mediated pro-apoptotic action was reversed by knockout of either p53 or ASK1, despite no increase in p53 apoptotic activity. Upon CDDP treatment, EA predominantly enhanced ROS generation, ASK1-p38/c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathway activation, and ultimately cell death, all of which were suppressed either by co-treatment of the NADPH oxidase (Nox) inhibitor Apocynin, or by knocking out its regulatory protein, receptor-interacting protein 1 (RIP1). These results demonstrate that in response to CDDP ICLs, TFAs promote p53-dependent apoptosis through the enhancement of the Nox-RIP1-ASK1-MAPK pathway activation, providing insight into the diverse pathogenetic mechanisms of TFAs according to the types of DNA damage.

BACKGROUND Many studies report the monitoring of catechins in tea samples by chromatographic techniques. Unfortunately, only a small number of screening assays for catechins exist as a result of the complexity of authentic standards for the respective calibration curves. In the present study, a single reference (SR) exhaustive assay for the simultaneous quantification of tea-derived catechins by liquid chromatography (LC) with photodiode array and fluorescence detectors based on relative molar sensitivity (RMS) was developed as a screening assay of common tea samples without respective calibration curves using authentic standards. RESULTS Three original SR standards were proposed based on flavonoid structures, evaluated by quantitative 1 H-NMR based on an indirect standard (1,4-bis(trimethylsilyl) benzene-d4 ) and successfully separated in a LC chromatogram. In tea samples with these added SR calculated based on RMS, the concentrations of eight tea-derived catechins could be measured with a relative SD of

1. Introduction The Hayabusa2/JAXA spacecraft has orbited and studied near-Earth object Ryugu [1]. Two sample collections have been performed and the spacecraft is currently on its way back to the Earth for an expected return in late 2020. A preliminary examination phase will follow [2], expected to elucidate the formation and evolution of Ryugu. Considering the limited amount of material that will be retrieved, a multi-analytical sequence is needed to maximize the scientific outcome and minimize sample loss. Among the possible laboratory techniques, IR spectroscopy is important in being totally non-destructive and comparable to remote sensing observations of small bodies [3]. Thanks to IR imaging micro-spectroscopy, it is possible to detect and study the spatial distribution of molecular bonds associated to minerals, water and organic compounds, and their co-localization [4]. We consider IR three dimensional (3D) micro-tomography (IR-CT) an excellent starting point in a multi-analytical sequence to be applied on returned samples [5]. Here we report IR hyperspectral measurements of carbonaceous chondrites as a rehearsal of IR-CT and IR hyperspectral imaging that will be part of the multi-analytical sequence of the “MIN-PET CG” Hayabusa2 team (mineralogy and petrology of coarse grains) led by T. Nakamura. 2. Methods We performed IR measurements in reflectance on bulk fragments of selected meteorites, and both in reflectance and transmittance on several isolated grains (sizing 20-50 µm) extracted from carbonaceous chondrites. We also analyzed individual grains of the Murchison CM meteorite prepared at Tohoku University (Japan) from three bulk samples: (1) unheated, (2) heated at 400°C, and (3) heated at 600°C [6]. The laboratory-controlled heating was applied to simulate potential heating undergone by Ryugu surface materials, as suggested by some Hayabusa2 observations [7]. Some of these Murchison grains were mounted on tungsten needles by means of a platinum welding performed in IEMN-Lille (France) with a focused ion beam microscope. Other grains were prepared at Tohoku University, mounted on carbon fibers using epoxy (Fig. 1). We analyzed the samples using an IR hyperspectral imaging and micro-tomography setup installed at the SMIS beamline of the SOLEIL synchrotron (France). This setup has already been used for analyzing Hayabusa samples from asteroid Itokawa [8]. FTIR data were collected using an Agilent Cary 670/620 microspectrometer. In transmission mode we used a X25 objective coupled with high magnification optics (providing an additional X2.5 magnification) placed in front of a 128x128 pixels FPA detector, to obtain a projected pixel size of ~0.66 µm on the focal plane, and a field of view of ~84 µm. IR-CT is performed in transmission mode using the method described by Dionnet et al. [8]. In reflection mode we used a X15 objective, with a projected pixel size of ~5.5 µm on the focal plane, and a field of view of ~700 µm (Fig. 1). In both cases we collected hyperspectral data: for each pixel we obtained an IR spectrum in the 850-3950 cm-1 spectral range. The spatial resolution was diffractionlimited for the whole investigated spectral range. 3. Results Infrared spectra show the presence of bending and stretching absorption bands of chemical bonds (C-H, OH, Si-O, C=O, etc.) of different functional groups, as expected from literature IR spectra of Murchison and other chondrites [9,10]. The relative intensities of these bands are found to vary among different grains, and their 3D spatial distribution is heterogeneous within individual grains (see Fig. 1). Noticeable differences are found between the IR spectra of unheated and heated Murchison samples, with a general trend of increasing the anhydrous to hydrated silicate content with increasing temperature, and reducing the organic content. Fig. 1. A typical IR reflectance hyperspectral map of an unheated Murchison sample mounted on a carbon needle (top left, microscope images in bright and dark field), with the detection of hydrated (bottom left) and anhydrous (bottom right) areas. The epoxy contribution can be clearly separated (top right). 4. Summary and Conclusions IR data provide a first quick look at the composition, abundance and 3D distribution of mineral phases and carbonaceous materials at the scale of a few micrometers. Once regions of interest are identified by IR measurements, thin sliced sections of the samples can be analyzed by more destructive techniques to retrieve the structure and the elemental and isotopic composition of the carbonaceous component and its mineral host, down to the nanometer scale [11]. In addition, the IR data are useful in the comparison with remote sensing observations of asteroid surfaces [7,12]. This top-down sequence will help us building a bridge between the remote sensing and in situ observations of Ryugu at macroscopic scale and the chemical and physical processes operating at the nanoscale. Acknowledgments The micro-spectroscopy measurements were supported by grants from Region Ile-de-France (DIM-ACAV) and SOLEIL. This work has been funded by the CNES (France) and by the ANR project CLASSY (Grant ANR-17-CE31-0004-02) of the French Agence Nationale de la Recherche. This work was partly supported by the French RENATECH network. References [1] Watanabe S. et al. (2019) Science 364, 268-272. [2] Tachibana S. et al. (2018) AGU Fall Meeting, abstract #P33C-3846. [3] Brunetto R. et al. (2011) Icarus 212, 896–910. [4] Dionnet Z. et al. (2018) Meteoritics & Planet. Sci. 53, 2608-2623. [5] Dionnet Z. et al. (2018) Microscopy and Microanalysis 24, 2100-2101. [6] Mogi K. et al. (2017) 80th Annual Meeting of the Meteoritical Society, Abstract #6225. [7] Kitazato K. et al. (2019) Science 364, 272-275. [8] Dionnet Z. et al. (2020) Meteoritics & Planet. Sci., in press. [9] Lantz C. et al. (2015) A&A 577, A41. [10] Beck P. et al. (2014) Icarus 229, 263-277. [11] Aléon-Toppani A. et al. (2020) Lunar and Planetary Science Conference 2682. [12] Hamilton V. et al. (2019) Nat. Astron. 3, 332–340.

Specularly light reflective fault plane interfaces known as Mirror-Slip Surfaces (MSS’s) are common in seismically active fault zones around the world and thus their role in controlling fault strength and stability is of great interest. MSS’s have been experimentally produced in simulated carbonate faults at relatively high (10-1-100 m/s) and low (10-7-10-5 m/s) sliding velocities (resp. HV and LV). However, their role in controlling fault mechanical properties at sub-seismic vs seismic fault-slip velocities remains enigmatic. With the aim to unravel the structural development of MSS’s with increasing shear displacement (rate) and effective normal stress, we conducted HV and LV shear deformation experiments on simulated faults composed of granular calcite. We employed a ring shear set-up in a HV rotary shear apparatus as well as a saw-cut assembly mounted in a triaxial cell, which enabled fault-slip tests under a wide range of slip velocities (v = 10-7 - 10-1 m/s) and effective normal stresses (σn ≈ 10 – 170 MPa). All experiments were carried out under room-dry conditions, at room temperature. Post-mortem microstructure analysis of recovered fragments was carried out through visual inspection, incident light and scanning electron microscopy, as well as using Raman spectroscopy.MSSs develop at sub-seismic slip velocities (v = 10-7 m/s) initially as visibly striated patches after 0.0062 m (σn ≈ 10 MPa), 0.004 m (σn ≈ 50 MPa) and 0.0026 m (σn ≈ 170 MPa) of shear displacement. The area covered by MSSs systematically increases with displacement to form continuous coatings after 0.042 (σn ≈ 10 MPa), 0.0062 m (σn ≈ 50 MPa) and 0.0036 m (σn ≈ 10 MPa). As displacement rate is increased (10-5 – 10-4 m/s) MSSs are no longer observed however continuous MSSs are visible again at seismic slip velocities (>10-1 m/s). Our microstructural analysis revealed that MSSs are layers of (nano)crystalline calcite some of which contain elongated nanofibrous structures. In addition, discrete, 3 - 20 micron-sized patches of amorphous carbon are produced at seismic slip velocities, and at sub-seismic velocities under high normal stresses (σn > 160 MPa). We could not however identify any microstructural characteristics that are diagnostics of MSSs produced at certain slip rates or normal stress.Our interpretation is that MSSs form by sintering of nm-sized particles within ultrafine-grained shear bands. With increasing shear displacement, MSS patches connect into continuous veneers. The formation of (continuous) MSSs at low as well as high sliding velocities in our experiments implies that natural MSSs are unreliable indicators for palaeoseismicity.

Natto is a well-known traditional Japanese food produced by fermenting soybeans with Bacillus subtilis var natto. Here we found that the water-soluble viscous fraction of natto inhibits sucrose- or glucose-induced hyperglycemia in silkworms. The water-soluble viscous fraction treated with DNase I, RNase A, and proteinase K, followed by phenol extraction also suppressed sucrose-induced hyperglycemia in silkworms. The enzyme-treated polysaccharide fraction of natto inhibits glucose uptake by Caco-2 cells, human intestinal epithelial cells. These findings suggest that the polysaccharide components of natto selected on the basis of their suppressive effects on sucrose-induced hyperglycemia in silkworms inhibit glucose uptake by human intestinal cells.

BACKGROUND Escherichia coli causes neonatal early-onset sepsis (EOS) that is associated with high mortality and increasing antibiotic resistance. Thus, we estimated the prevalence, antibiotic susceptibility and risk factors for colonization of E. coli in premature infants at birth and characterized the pathogenicity of the isolates. METHODS A prospective surveillance study was conducted at three Japanese perinatal centers between August 2014 and February 2017. Infants weighing

Background Concomitant chemoradiotherapy (CCRT) produces severe mucositis and swallowing dysfunction, often resulting in malnutrition. Intensive nutrition support (INS) in addition to percutaneous endoscopic gastrostomy (PEG) is reported to decrease adverse effects during CCRT. Patients and Methods Fifty-eight patients with oropharyngeal cancer treated by CDDP-based CCRT were retrospectively analyzed. Twenty-nine patients treated with INS in addition to PEG were classified as INS group, and other 29 patients treated with PEG but without INS were classified as control group. Results INS in addition to PEG significantly increased calorie intake in the second half of CCRT and reduced adverse events including mucositis (p=0.0019), leukopenia (p=0.04), and renal function (p=0.006). Moreover, 21 out of 29 patients had successfully administration of 200mg/m2 or more of CDDP, while only 10 out of 29 patients had enough amount of CDDP in control group. Conclusions These results suggest that INS in addition to prophylactic PEG not only decreases adverse effects but also may potentially improve oncological outcome of the patients with oropharyngeal cancer treated by CCRT.

Food-borne trans-fatty acids (TFAs) are mainly produced as byproducts during food manufacture. Recent epidemiological studies have revealed that TFA consumption is a major risk factor for various disorders, including atherosclerosis. However, the underlying mechanisms in this disease etiology are largely unknown. Here we have shown that TFAs potentiate activation of apoptosis signal-regulating kinase 1 (ASK1) induced by extracellular ATP, a damage-associated molecular pattern leaked from injured cells. Major food-associated TFAs such as elaidic acid (EA), linoelaidic acid, and trans-vaccenic acid, but not their corresponding cis isomers, dramatically enhanced extracellular ATP-induced apoptosis, accompanied by elevated activation of the ASK1-p38 pathway in a macrophage-like cell line, RAW264.7. Moreover, knocking out the ASK1-encoding gene abolished EA-mediated enhancement of apoptosis. We have reported previously that extracellular ATP induces apoptosis through the ASK1-p38 pathway activated by reactive oxygen species generated downstream of the P2X purinoceptor 7 (P2X7). However, here we show that EA did not increase ATP-induced reactive oxygen species generation but, rather, augmented the effects of calcium/calmodulin-dependent kinase II-dependent ASK1 activation. These results demonstrate that TFAs promote extracellular ATP-induced apoptosis by targeting ASK1 and indicate novel TFA-associated pathways leading to inflammatory signal transduction and cell death that underlie the pathogenesis and progression of TFA-induced atherosclerosis. Our study thus provides insight into the pathogenic mechanisms of and proposes potential therapeutic targets for these TFA-related disorders.

Illudin S from mushroom, such as Omphalotus japonicus and illudens, is a natural sesquiterpene analog with strong anti-tumor and antiviral activities. These illudins compounds are highly effective against various drug-resistant cancers that show extreme cytotoxicity an in vitro assay. However, it is difficult to obtain a sufficient amount of highly pure illudin S from a natural product by simple, efficient and low-cost purification techniques. Here, we offer to apply the high-speed countercurrent chromatography for the preparative purification of illudin S from mushroom extract. For a two-solvent system, the optimal condition of hexane/ethyl acetate/methanol/water (1/5/1/5, v/v/v/v) was optimized to obtain pure illudin S from a crude extract. This purified component was evaluated by liquid chromatography (high-purity >99%) and tandem mass spectrometry. The yield amounts of illudin S (1.3 mg/about 10 g Omphalotus japonicus) at one running are determined by liquid chromatographic calibration. It is concluded that by requiring a natural material and cost-effectiveness, our method represents a significant improvement over complicated techniques for the purification of illudin S from natural materials.

The objective of this study was to elucidate in detail the Hg adsorption performance of Cl-loaded carbons obtained after chlorination of rice husk char (RC). Firstly, chlorine content/morphology/porosity of Cl-loaded carbons prepared were investigated. Subsequently, Hg adsorption performance of Cl-loaded carbon was tested. The effect of Cl on Hg adsorption was then investigated by comparing the adsorption performance of Cl-loaded carbons prepared from RC and demineralized RC (DRC). Cl content of RC and DRC reached a maximum value at 600 °C, and then decreased by 1000 °C. The pore properties of RC chlorinated residue increased with increasing chlorination temperature. The Hg adsorption performance of the RC chlorinated residues increased with increasing chlorination temperature. The maximum Hg adsorption capacity of RC chlorinated residue obtained at 1000 °C, 10min reached 620 mg/g; the capacity of chlorinated residue treated with DRC at 1000 °C, 10min was larger than that of DRC chlorinated at 600 °C, which is largest Cl content. The adsorption kinetics and isotherm could be expressed by pseudo-first-order and Langmuir equations, respectively. The comparison of the porosity and Hg adsorption of DRC and RC chlorinated residue obtained at 1000 °C, 10min indicated that Cl-adsorbed on the carbon in RC during chlorination may also be involved in Hg adsorption.

Highly localized slip zones developed within ductile shear zones, such as pseudotachylite bands occurring within mylonitic fabric rocks, are frequently interpreted as evidence for earthquake nucleation and/or propagation within the ductile regime. To understand brittle/frictional shear localization processes in ductile shear zones and to relate these to earthquake nucleation and propagation, we performed tests with large change in velocity on a brine-saturated, 80:20 (wt.%) mixture of halite and muscovite gouge after forming a mature mylonitic structure through frictional-viscous flow. The direct effect a on shear strength that occurs in response to an instantaneous upward velocity-step is an important parameter in determining the nature of seismic rupture nucleation and propagation. We obtained reproducible results regarding low velocity mechanical behavior compared with previous work, but also obtained new insights into effects of sudden increases in slip velocity on localization and strength evolution, at velocities above a critical velocity Vc (∼20 μm/s). We found that once a ductile, mylonitic structure has developed in a shear zone, subsequent cataclastic deformation is consistently localized in a narrow zone. This switch to localized deformation is controlled by the imposed velocity, and becomes most apparent at velocities above Vc. In addition, the direct effect drops rapidly when the velocity exceeds Vc. This implies that slip can accelerate towards seismic velocities almost instantly and without much loss of fracture energy, once Vc is exceeded. Obtaining a measure for Vc in natural faults is therefore of key importance for understanding earthquake nucleation and propagation in the brittle-ductile transitional regime.

A lysozyme-chitosan conjugate preparation (LYZOX), produced from egg white lysozyme and chitosan by Maillard reaction, is a commercial product developed as a cosmetic ingredient or food additive. Effects of LYZOX on in vitro growth of Candida albicans were examined. C. albicans cells were treated with LYZOX for 3 hrs, and then washed and cultured for an additional 16 hrs in modified RPMI1640 medium. Mycelial growth of C. albicans was clearly inhibited by more than 100 μg/ml of LYZOX in a concentration-dependent manner. On the other hand, corresponding concentration of chitosan or lysozyme or their mixture only scarcely showed clear inhibitory effect. Similarly, anti-Candida activity of the combination of LYZOX and decanoic acid, a middle-chain fatty acid, was also examined. Inhibitory activity of this combination against mycelial growth of C. albicans was very potent and appeared synergistic, since fractionated inhibitory concentration (FIC) index for 70% growth inhibition was calculated to be 0.20. Oral application of this combination improved the symptoms of Candida-infected-tongue in an experimental murine candidiasis model. On the basis of these results, the possible application of LYZOX as a new functional product with anti-candida activity was discussed.