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Gut microbial lipopolysaccharide (LPS) induces endotoxemia, an independent risk factor for cardiovascular disease (CVD). However, no studies have demonstrated how structural differences in each bacterial LPS contribute to endotoxemia. Here, we investigated the effects of different acyl chains in the lipid A moiety of LPS on endotoxemia and the subsequent immune response and atherosclerotic plaque formation.ApoeE. LPS administration induced endotoxemia, but B. LPS and saline did not. In E. LPS-treated mice, total plaque areas in the aortic root were significantly increased, and neutrophil accumulation and increased formation of neutrophil extracellular traps (NETs) were observed at the plaque lesions, but not in B. LPS-treated mice. A single dose of E. LPS significantly increased the accumulation of neutrophils in plaque lesions on day 3, and NET formation on day 7. E. LPS also increased interleukin-1 beta (IL-1β) production in plaque lesions on day 7. Furthermore, NET formation and IL-1β production were also observed in human coronary plaques.We identified a previously unknown link between structural differences in LPS and atherosclerosis. Lowering microbial LPS activity may reduce NET formation in plaques and prevent CVD progression.

We conducted a series of numerical simulations to understand the effect of the initiation process of cylindrical high explosives on the blast-wave behavior and peak overpressure distribution. The first case involved the explosion of a cylindrical high explosive whose length-to-diameter ratio was equal to 2 and that was vertically placed above the ground surface. The initiation point was at the top of the high explosive. The initiation process induced the detonation momentum directed from top to bottom, and the detonation products forcefully hit the ground surface, resulting in a higher peak overpressure on the ground surface in comparison with the case using an isothermal constant-pressure volume. After the blast wave expanded far from the initiation point, the computed peak overpressures of the two approaches showed good agreement with those from experiments. The second case involved the explosion of a cylindrical high explosive whose length-to-diameter ratio was unity and that was placed in air. The initiation point was the one end side of the high explosive. The blast wave was divided into three regions that originated from the detonation in the high explosive, an oblique shock wave in air, and a bridge wave connected with them, thus causing an azimuthal distribution of peak overpressure. The highest peak overpressure values were computed in the bridge wave region. To understand the propagation behavior of the blast wave, we should thoroughly observe how and when all the waves affecting the blast-wave behavior are generated and how they propagate and interact with each other.

An experimental investigation was conducted to compare the blast mitigation performances of water layers, whose mass ratios to an explosive were $$ m_{{\text{W}}} /m_{{\text{E}}} = 12.2,44.5,\;{\text{and}}\;107.2 $$ , with water droplets surrounding the explosive. The blast waveforms were measured using pressure transducers, and the motion of the water layer was recorded using a high-speed camera. When mW/mE was equivalent between the water layer and water droplets, the water layer exhibited less mitigation of the peak overpressure and positive impulse than the water droplets. The results demonstrated high efficiency of the water droplets in blast mitigation and the existence of an optimal apparent density of the water barrier. The velocities of the water layers determined using high-speed photography agreed with the prediction model of the barrier material accelerated by explosion. It suggested that the primary cause of the blast overpressure mitigation by the water layer was the allocation of the explosion energy into the kinetic energy of the water.

This study validated a two-phase compressible flow model considering elasto-plastic porous foams. The numerical data were compared with the previous experimental results in terms of the interaction between the planar shock wave and the porous foams and the mitigation effect of a porous foam filling a straight tube on a blast wave. The porous foams in the shock tube interacted with a planar shock wave. The drag between the shocked air and the foams reduced the shock wave strength. Moreover, the flexible foam was significantly deformed by the shock wave. The validation results confirmed good agreement and consistency between the numerical and experimental data. The mitigation effect on the blast wave caused by a high explosive, where the main parameter for comparison was the location of a rigid porous foam layer inside the straight tube, was investigated. In the first case, the porous foam plate was placed on the floor, whereas in the second case, the porous foam plates were placed on the floor, sidewalls and ceiling. The total energy transferred between the porous foam and the shocked air was computed to quantitatively understand the mitigation mechanism of the porous foam on the blast wave. The heat transfer was a dominant factor for the energy transfer from the shocked air to the porous foams. The second case further mitigated the blast wave outside, and the increment of the interface area of the air/porous foam greatly affected the blast wave mitigation.

Polyamines are aliphatic hydrocarbons with terminal amino groups and are essential for biological activities. It has been reported that polyamines have health-promoting effects in animals, such as the extension of lifespan by polyamine intake. The identification of a high polyamine-producing bacterium from foods could lead to the development of a novel probiotic candidate. We aimed to identify high polyamine-producing bacteria from food, and isolated and collected bacteria from vegetables and fermented foods produced in Japan. We successfully acquired

In this work, we studied detonation in condensed-phase explosives of PETN and the oblique shock waves in the surrounding fluid. The surrounding fluid was modeled as an ideal gas equation of state using the specific heat ratio as a parameter. Depending on the specific heat ratio, four types of flow structures were observed behind the oblique shock wave in the ideal gas. We measured the detonation/shock angles and the contact angle between the detonation products and the ideal gas. When the specific heat ratio was greater than the critical value, the oblique shock wave was detached from the detonation front at the PETN/ideal gas interface. When attached, three types of waves are observed, depending on the specific heat ratio: a strong oblique shock wave, strong and weak oblique shock waves which meet at the triple point as well as a weak oblique shock wave. To understand the properties of the flow near the detonation and the oblique shock waves, they were modeled as planar Chapman–Jouguet (CJ) detonation in PETN and as oblique shock waves in ideal gas. They were theoretically estimated as (1) Prandtl–Meyer expansion of the detonation products from the CJ state, and (2) oblique shock waves around a wedge using oblique shock theory or around a cone using the Taylor–Maccoll equation. From the flow models, we obtained a solution for the pressure equilibrium and parallel flows between the detonation products and ideal gas under the assumption that the wedge and cone angles correspond to the contact angle between them. For the attached cases, the solution was consistent with the simulated observations at the PETN/ideal gas interface. From the flow models, the maximum deflection angles for the detonation products and the ideal gas were obtained, and their magnitude correlations used to classify the four types of flow.

We report numerical simulations undertaken to understand the effects of a protective dike near an underground high-explosive storage facility. Our numerical model allowed us to estimate the peak overpressure of a blast wave around an underground magazine with or without a dike. We varied the internal length-to-diameter ratio of the underground magazine to compare the effects of magazine length. We found that the dike prevented the blast wave and detonation products from expanding along the exit direction and mitigated the peak overpressure near the dike. Our simulated results for peak overpressures outside the magazine on the ground agreed well with experimental results. The azimuthal characteristics, how the peak overpressure was reduced by the increment of the azimuth angle, were independent of the internal length-to-diameter ratio of the magazine. The presence of a dike, however, does change the shape of the iso-peak overpressure zone around the magazine exit which would determine the explosive safety quantity–distance. With a dike, the iso-peak overpressure zone is a circle, and it is an ellipse without the dike on the ground. The parameters to describe these shapes can be expressed as a linear function of the radius of the iso-peak overpressure zone of a surface explosion without any models on the ground.

Clostridioides difficile causes nosocomial antibiotic-associated diarrhea on a global scale. Susceptibility to C. difficile infection (CDI) is influenced by the composition and metabolism of gut microbiota, which in turn are affected by diet. However, the mechanism underlying the interplay between diet and gut microbiota that modulates susceptibility to CDI remains unclear. Here, we show that a soy protein diet increases the mortality of antibiotic-treated, C. difficile-infected mice while also enhancing the intestinal levels of amino acids (aas) and relative abundance of Lactobacillus genus. Indeed, Ligilactobacillus murinus-mediated fermentation of soy protein results in the generation of aas, thereby promoting C. difficile growth, and the process involves the anchored cell wall proteinase PrtP. Thus, mutual interaction between dietary protein and the gut microbiota is a critical factor affecting host susceptibility to CDI, suggesting that dietary protein sources can be an important determinant in controlling the disease.

We conducted a series of numerical simulations to understand the effect of the shape of a partially confined geometry on blast wave strength, including its scaling method. We referred to an...

This study explored the practicality of a two-phase flow model for water droplets in elucidating the blast mitigation mechanism of water droplets. To validate the model, the numerical data were compared with previous experimental results in terms of the evaporation of a single water droplet, and the interaction between the shock/blast waves and water droplets. Results of the validation confirmed good agreement and consistency between both data by combining the existing models for droplet breakup. Next, the blast-mitigation effect of water droplets sprayed around a high explosive was investigated, where the main parameter was the layer radius. A thicker layer further mitigated the blast wave, but there was a limit to the blast-mitigation effect when the layer radius was greater than a critical value. The high-temperature and high-pressure detonation products should interact with the water droplets, which absorb their momentum and energy. The critical layer radius was equivalent to the dispersion distance of the detonation products. To quantitatively understand the blast-mitigation mechanism of water droplets, the transferred energies by drag force, convective heat transfer, radiative heat transfer, and evaporation were computed. A strong correlation between the blast wave strength and the sum of transferred energies by the drag force and convective heat transfer was obtained in the case that the initial diameter of the water droplets was of the order of millimeters.

A two-dimensional numerical simulation of the interaction between a shock wave and a particle cloud curtain (PCC) in a shock tube was conducted to develop the numerical method and to understand how the particle layer mitigates the shock wave. In the present study, computational fluid dynamics/the discrete element method in conjunction with drag force and convective heat transfer models were used to separately solve the continuum fluid and particle dynamics. The applicability of the method to the gas flow and particles was validated through comparison with gas–particle shock-tube experiments, in which the PCC was generated by free fall, and particles initially had a gradient of its volume fraction and falling velocity in height. When the incident shock wave interacted with the PCC, it was reflected from and transmitted through the PCC. The transmitted shock wave had a curved front because the initial gradient in the volume fraction of particles locally changed the interaction between the shock wave and the particles. We calculated the effects of the drag force and heat transfer in mitigating the strength of the transmitted shock wave. The propagation of the transmitted and reflected shock waves and the motion of the PCC induced by the gas flow behind the shock wave agreed well with previous experimental data. After the interaction between the gas flow and the PCC, drag force and heat transfer were activated by the gradients in pressure, velocity, and temperature between them, and the gas flow lost momentum and energy, which weakened the transmitted shock wave. At the same time, the PCC gained momentum and energy and was dispersed. The contact forces between two particles affected the local dispersion of the PCC.

Faecal lipopolysaccharides (LPS) have attracted attention as potent elements to explain a correlation between the gut microbiota and cardiovascular disease (CVD) progression. However, the underlying mechanism of how specific gut bacteria contribute to faecal LPS levels remains unclear. We retrospectively analysed the data of 92 patients and found that the abundance of the genus Bacteroides was significantly and negatively correlated with faecal LPS levels. The controls showed a higher abundance of Bacteroides than that in the patients with CVD. The endotoxin units of the Bacteroides LPS, as determined by the limulus amoebocyte lysate (LAL) tests, were drastically lower than those of the Escherichia coli LPS; similarly, the Bacteroides LPS induced relatively low levels of pro-inflammatory cytokine production and did not induce sepsis in mice. Fermenting patient faecal samples in a single-batch fermentation system with Bacteroides probiotics led to a significant increase in the Bacteroides abundance, suggesting that the human gut microbiota could be manipulated toward decreasing the faecal LPS levels. In the clinical perspective, Bacteroides decrease faecal LPS levels because of their reduced LAL activity; therefore, increasing Bacteroides abundance might serve as a novel therapeutic approach to prevent CVD via reducing faecal LPS levels and suppressing immune responses.

Bifidobacteria are members of the human intestinal microbiota, being numerically dominant in the colon of infants, and also being prevalent in the large intestine of adults. In this study, we measured the concentrations of major polyamines (putrescine, spermidine, and spermine) in cells and culture supernatant of 13 species of human indigenous Bifidobacterium at growing and stationary phase. Except for Bifidobacterium bifidum and Bifidobacterium gallicum, 11 species contained spermidine and/or spermine when grown in Gifu-anaerobic medium (GAM). However, Bifidobacterium scardovii and Bifidobacterium longum subsp. infantis, which contain spermidine when grown in GAM, did not contain spermidine when grown in polyamine-free 199 medium. Of the tested 13 Bifidobacterium species, 10 species showed polyamine transport ability. Combining polyamine concentration analysis in culture supernatant and in cells, with basic local alignment search tool analysis suggested that novel polyamine transporters are present in human indigenous Bifidobacterium. Abbreviations: Put: putrescine; Spd: spermidine; Spm: spermine; GAM: Gifu anaerobic medium; BHI: brain-heart infusion Of the tested 13 Bifidobacterium species in this study, 10 species showed polyamine transport ability.

Lauric acid (LA) has a broad spectrum of anti-microbiological activities against enveloped viruses and various bacteria, and might be useful to protect against microbial infection and control the balance and distribution of bacteria in human gut microbiota. It is not necessarily more difficult to measure antimicrobial activity the traditional way, but it is, however, more laborious. In the present study, we developed a new method to measure the antimicrobial activity of LA in multiple samples with a microplate reader. A “test complex” (TC) was produced consisting of 100 μL of agar medium with LA in the bottom layer and 300 μL of broth in the top layer in 96-well deep-well microplates. Afterward, analysis of the broth in the top layer showed that the antimicrobial activity was the same as that of the “control complex,” (CC) which consisted of 100 μL of agar medium in the bottom layer and 300 μL of broth with LA in the top layer. Furthermore, evaluation of the antimicrobial effect of the TC when using a microplate reader was the same as that with the use of the colony counting method. The colony counting method has confirmed that the antimicrobial activity of LA when bacteria are inoculated into the broth was equivalent between CC and TC, and we validated this by correlating the number of bacteria with absorbance. In addition, the broth itself in TC was transparent enough that the turbidity of broth can be used as an index of the number of bacteria, which enabled the use of a microplate reader for multiple samples. For human gut microbes, LA was shown to have low antimicrobial activity against commensal lactic acid bacteria, but high antimicrobial activity against pathogenic Bacteroides and Clostridium, suggesting that LA might modulate intestinal health, as confirmed by the proposed method.

Two-dimensional explosion experiments were conducted to discuss the interaction between a blast wave and sand and show the mitigation effect of the sand on the blast wave. The explosive used was a detonating cord 1.0 m in length, which was initiated in a sand hill shaped like a triangular prism and whose cross section was an isosceles triangle with base angles of 30 $$^\circ $$ . Sand-hill heights of 30 and 60 mm were used as parameters to discuss the effect of sand mass upon blast-wave strength. The interaction of the blast wave with the sand/air interface causes multiple peaks in the blast wave, which are induced by successive transmissions at the interface. The increase in the sand mass further mitigates the blast parameters of peak overpressure and positive impulse. The results of this experiment can be utilized to validate the numerical method of solving the problem of interaction between a compressible fluid and a particle layer.

This paper investigates explosions in a straight square tube in order to understand the mitigation effect of water on blast waves that emerge outside. Numerical simulations are used to assess the effect of water that is filled inside the tube. The water reduces the peak overpressure at the tube exit and outside, which agrees well with the experimental data. The increases in the kinetic and internal energies of the water are estimated, and the internal energy transfer at the air/water interface is shown to be an important factor in mitigating the blast wave on the ground in the present numerical method. Two mechanisms of the energy transfer are proposed in the present study. Initially, the strong shock wave reflects off and transmits water. A high-energy transfer into the water from air is promoted by the shock compression of water. Subsequently, as the shock wave propagates along the water surface, the air is adiabatically compressed continuously, and the pressure and temperature differences between the shocked-air and water induce a more gradual transfer of internal energy into the water.

This paper investigates explosions in a straight square tube in order to understand the mitigation effect of water on blast waves that emerge outside. Numerical simulations are used to assess the effect of water that is put inside the tube. The water reduces the peak overpressure outside, which agrees well with the experimental data. The increases in the kinetic and internal energies of the water are estimated, and the internal energy transfer at the air/water interface is shown to be an important factor in mitigating the blast wave in the present numerical method.

A subsurface magazine has an explosive storage chamber, a horizontal passageway, and a vertical shaft for vent. It was proposed and legislated in Japan. The authors found that small amount of water on the floor of its storage chamber mitigated the blast pressure remarkably. The mechanism of the mitigation has been studied, however, it is not still well understood. In this study, the explosion in a transparent, square cross section, and straight tube was carried out to examine the mechanism of blast-wave mitigation by water. The arrangement and amount of water in the tube were varied for five ways. The dependence of mitigation effect on the arrangement and amount of water was evaluated by measuring the blast pressures in the tube and outside the tube. The results of this study concluded that the mitigation of blast wave by water is mainly due to the interaction between the explosion and the water very near the explosion point. On the contrary, the water at other part of the tube was found to strengthen the blast pressure.

Recent studies have reported that polyamines in the colonic lumen might affect animal health and these polyamines are thought to be produced by gut bacteria. In the present study, we measured the concentrations of three polyamines (putrescine, spermidine, and spermine) in cells and culture supernatants of 32 dominant human gut bacterial species in their growing and stationary phases. Combining polyamine concentration analysis in culture supernatant and cells with available genomic information showed that novel polyamine biosynthetic proteins and transporters were present in dominant human gut bacteria. Based on these findings, we suggested strategies for optimizing polyamine concentrations in the human colonic lumen via regulation of genes responsible for polyamine biosynthesis and transport in the dominant human gut bacteria.

We have recently generated a highly efficient 1,2-α-l-fucosynthase (BbAfcA N423H mutant) by protein engineering of 1,2-α-l-fucosidase from Bifidobacterium bifidum JCM 1254. This synthase could specifically introduce H-antigens (Fucα1-2Gal) into the non-reducing ends of oligosaccharides and in O-linked glycans in mucin glycoprotein. In the present study, we show an extended application of the engineered 1,2-α-l-fucosynthase by demonstrating its ability to insert Fuc residues into N- and O-glycans in fetuin glycoproteins, GM1 ganglioside, and a plant-derived xyloglucan nonasaccharide. This application study broadens the feasibility of this novel H-antigen synthesis technique in functional glycomics.

This paper numerically visualizes explosion phenomena in order to discuss blast wave characteristics with a two-dimensional axisymmetric room model. After the shock wave exits via an opening, the blast wave propagates into open space. In the present study, a parametric study was conducted to determine the blast wave characteristics from the room exit by changing the room shape and the mass of the high explosive. Our results show that the blast wave characteristics can be correctly estimated using a scaling factor proposed in the present paper that includes the above parameters. We conducted normalization of the peak overpressure curve using the shock overpressure at the exit and the length scale of the room volume. In the case where the scaling factor has the same value, the normalized peak overpressure curve does not depend on the calculation conditions, and the scaling factor describes the blast wave characteristics emerging from the current room model.

sCancer cells show a bias toward the glycolytic system over the conventional mitochondrial electron transfer system for obtaining energy. This biased metabolic adaptation is called the Warburg effect. Cancer cells also exhibit a characteristic metabolism, a decreased heme synthesizing ability. Here we show that heme synthesis and the Warburg effect are inversely correlated. We used human gastric cancer cell lines to investigate glycolytic metabolism and electron transfer system toward promotion/inhibition of heme synthesis. Under hypoxic conditions, heme synthesis was suppressed and the glycolytic system was enhanced. Addition of a heme precursor for the promotion of heme synthesis led to an enhanced electron transfer system and inhibited the glycolytic system and vice versa. Enhanced heme synthesis leads to suppression of cancer cell proliferation by increasing intracellular reactive oxygen species levels. Collectively, the promotion of heme synthesis in cancer cells eliminated the Warburg effect by shifting energy metabolism from glycolysis to oxidative phosphorylation.

The human gut microbiota established during infancy has persistent effects on health. In vitro studies have suggested that human milk oligosaccharides (HMOs) in breast milk promote the formation of a bifidobacteria-rich microbiota in infant guts; however, the underlying molecular mechanism remains elusive. Here, we characterized two functionally distinct but overlapping fucosyllactose transporters (FL transporter-1 and -2) from Bifidobacterium longum subspecies infantis. Fecal DNA and HMO consumption analyses, combined with deposited metagenome data mining, revealed that FL transporter-2 is primarily associated with the bifidobacteria-rich microbiota formation in breast-fed infant guts. Structural analyses of the solute-binding protein (SBP) of FL transporter-2 complexed with 2′-fucosyllactose and 3-fucosyllactose, together with phylogenetic analysis of SBP homologs of both FL transporters, highlight a unique adaptation strategy of Bifidobacterium to HMOs, in which the gain-of-function mutations enable FL transporter-2 to efficiently capture major fucosylated HMOs. Our results provide a molecular insight into HMO-mediated symbiosis and coevolution between bifidobacteria and humans., ビフィズス菌におけるヒトへの適応進化を発見 --母乳オリゴ糖トランスポーターの獲得形質がビフィズスフローラ形成を促す--. 京都大学プレスリリース. 2019-09-05.

The interaction of a shock wave and particles filling the inside of a straight tube was numerically investigated to understand the mitigation mechanism on a blast wave outside the tube. A shock wave propagating along the particle layer inside the straight tube induced differences in the velocity and temperature between the particle layer and shocked air, inducing energy transfer through a drag effect, heat transfer, and nozzling term. Because the particle layer hardly moved inside the straight tube, the drag effect and nozzling term were too small to mitigate the blast wave. On the other hand, the heat transfer from the air to the particle layer absorbed several tens of percent of the energy released by the high explosive and was the dominant factor in mitigating the blast wave. To estimate the effect of the heat transfer between the particle layer and shocked air, we proposed a novel index estimated by the shocked-air properties, using the Rankine–Hugoniot relation. The numerical data for the heat transfer rate were simply and adequately estimated by the novel index, which indicated that the shocked-air properties were responsible for the heat transfer rate used to determine the mitigation of the blast wave.

This paper visualizes explosions in a subsurface magazine model constructed underground to mitigate the effects of blast waves. Numerical simulations discuss the effect of water that is put inside the magazine model. In the case of the explosion inside the magazine with water, the peak overpressure on the ground becomes smaller than that in the case of the explosion on the ground. The peak overpressures on the ground agree with those in the previous experiment. The increases of kinetic and internal energies of water are then estimated, and that the internal energy transfer at the interface of water and air is one of important factors to mitigate the blast wave on the ground in the present numerical method. As high-pressure gas at the exit of the magazine model drives the blast wave, the exit impulse and pressure are calculated and well reduced in the case with water inside the magazine model. Our study confirms that the exit pressure can scale the peak overpressure on the ground.

Fucα1-2 Gal linkages, or H-antigens, constitute histo-blood group antigens and are involved in various physiological processes. In addition, recent studies have shown that the H-antigen-containing glycans play an important role, not only in establishing harmonious relationship between gut microbes and the host, but also in preventing gut dysbiosis-related diseases. Therefore, development of an efficient method for introducing Fuc residue at Gal residue at the nonreducing end of glycans via α-(1→2) linkage is desired for research as well as medicinal purposes. In this study, we succeeded in derivatizing inverting 1,2-α-l-fucosidase (AfcA) into a highly efficient 1,2-α-l-fucosynthase. The synthase specifically synthesized H type 1-, type 2-, type 3- and type 4-chain-containing oligosaccharides with yields of 57-75% based on acceptor depletion. The synthase was also able to specifically introduce Fuc residues into Lewis a/x antigens to produce Lewis b/y antigens, with yields of 43% and 62%, respectively. In addition, the enzyme efficiently introduced H-antigens into sugar chains of porcine gastric mucins, as revealed by lectin blotting and mass spectroscopy analysis of the sugars. Detailed acceptor specificity analysis using various monosaccharides and oligosaccharides unraveled unique substrate recognition feature of this synthase at the subsite (+1), which can be explained by our previous X-ray crystallographic study of AfcA. These results show that the synthase developed in this study could serve as an alternative to other H-antigen synthesis methods involving α-1,2-fucosyltransferases and retaining α-fucosidase.

Recent studies have indicated that polyamines produced by gut microbes significantly influence host health; however, little is known about the microbial polyamine biosynthetic pathway except for that in Escherichia coli, a minor component of the gastrointestinal microbiota. Here, we investigated the polyamine biosynthetic ability of Bacteroides thetaiotaomicron, a predominant gastrointestinal bacterial species in humans. High-performance liquid chromatography analysis revealed that B. thetaiotaomicron cultured in polyamine-free minimal medium accumulated spermidine intracellularly at least during the mid-log and stationary phases. Deletion of the gene encoding a putative carboxyspermidine decarboxylase (casdc), which converts carboxyspermidine to spermidine, resulted in the depletion of spermidine and loss of decarboxylase activity in B. thetaiotaomicron. The Δcasdc strain also showed growth defects in polyamine-free growth medium. The complemented Δcasdc strain restored the spermidine biosynthetic ability, decarboxylase activity, and growth. These results indicate that carboxyspermidine decarboxylase is essential for synthesizing spermidine in B. thetaiotaomicron and contributes to the growth of this species.