Gut microbiota-derived lipid metabolites facilitate regulatory T cell differentiation.

Commensal bacteria-derived metabolites are critical in regulating the host immune system. Although the impact of gut microbiota-derived hydrophilic metabolites, such as short-chain fatty acids, on immune cell functions and development has been well documented, the immunomodulatory effects of gut microbiota-derived lipids are still of interest. Here, we report that lipid extracts from the feces of specific-pathogen-free (SPF), but not germ-free (GF), mice showed regulatory T (Treg)-cell-inducing activity. We conducted RP-HPLC-based fractionation and liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based lipidome profiling and identified two bioactive lipids, 9,10-dihydroxy-12Z-octadecenoic acid (9,10-DiHOME) and all-trans retinoic acid (atRA), with Treg-inducing activity in vitro. The luminal abundance of 9,10-DiHOME in the large intestine was significantly decreased by dextran sulfate sodium (DSS)-induced colitis, indicating that 9,10-DiHOME may be a potential biomarker of colitis. These observations implied that commensal bacteria-derived lipophilic metabolites might contribute to Treg development in the large intestine.

A combinatorial characterization scheme for high-throughput investigations of hydrogen storage materials.

In order to increase measurement throughput, a characterization scheme has been developed that accurately measures the hydrogen storage properties of materials in quantities ranging from 10 ng to 1 g. Initial identification of promising materials is realized by rapidly screening thin-film composition spread and thickness wedge samples using normalized IR emissivity imaging. The hydrogen storage properties of promising samples are confirmed through measurements on single-composition films with high-sensitivity (resolution <0.3 µg) Sievert's-type apparatus. For selected samples, larger quantities of up to ∼100 mg may be prepared and their (de)hydrogenation and micro-structural properties probed via parallel in situ Raman spectroscopy. Final confirmation of the hydrogen storage properties is obtained on ∼1 g powder samples using a combined Raman spectroscopy/Sievert's apparatus.

Complex hydrides with (BH(4))(-) and (NH(2))(-) anions as new lithium fast-ion conductors.

Some of the authors have reported that a complex hydride, Li(BH(4)), with the (BH(4))(-) anion exhibits lithium fast-ion conduction (more than 1 x 10(-3) S/cm) accompanied by the structural transition at approximately 390 K for the first time in 30 years since the conduction in Li(2)(NH) was reported in 1979. Here we report another conceptual study and remarkable results of Li(2)(BH(4))(NH(2)) and Li(4)(BH(4))(NH(2))(3) combined with the (BH(4))(-) and (NH(2))(-) anions showing ion conductivities 4 orders of magnitude higher than that for Li(BH(4)) at RT, due to being provided with new occupation sites for Li(+) ions. Both Li(2)(BH(4))(NH(2)) and Li(4)(BH(4))(NH(2))(3) exhibit a lithium fast-ion conductivity of 2 x 10(-4) S/cm at RT, and the activation energy for conduction in Li(4)(BH(4))(NH(2))(3) is evaluated to be 0.26 eV, less than half those in Li(2)(BH(4))(NH(2)) and Li(BH(4)). This study not only demonstrates an important direction in which to search for higher ion conductivity in complex hydrides but also greatly increases the material variations of solid electrolytes.

Regulation of inflammatory response of macrophages and induction of regulatory T cells by using retinoic acid-loaded nanostructured lipid carrier.

Immunomodulatory function of all-trans retinoic acid (ATRA) has been gathering much attention for the therapy of autoimmune diseases. ATRA is a chemically unstable molecule which requires proper formulation for targeted delivery. Here we examined nanostructured lipid carrier (NLC) for the formulation of ATRA. NLC is a representative nanoparticle formulation especially suited for oral delivery. We established the preparation procedures of ATRA-containing NLC (NLC-RA) which minimizes the degradation of ATRA during the preparation process. NLC-RA thus obtained was taken up by macrophages and induced anti-inflammatory response via suppressing NF-κB signaling as well as via enhancing the production of anti-inflammatory cytokines. Moreover, NLC-RA enhanced differentiation of naïve T cells to regulatory T cells in the co-culture system with dendritic cells. These results suggest that NLC-RA is a promising alternative therapy for the autoimmune diseases especially intestinal bowel disease.

A complex hydride lithium superionic conductor for high-energy-density all-solid-state lithium metal batteries.

All-solid-state batteries incorporating lithium metal anode have the potential to address the energy density issues of conventional lithium-ion batteries that use flammable organic liquid electrolytes and low-capacity carbonaceous anodes. However, they suffer from high lithium ion transfer resistance, mainly due to the instability of the solid electrolytes against lithium metal, limiting their use in practical cells. Here, we report a complex hydride lithium superionic conductor, 0.7Li(CB9H10)-0.3Li(CB11H12), with excellent stability against lithium metal and a high conductivity of 6.7 × 10-3 S cm-1 at 25 °C. This complex hydride exhibits stable lithium plating/stripping reaction with negligible interfacial resistance (<1 Ω cm2) at 0.2 mA cm-2, enabling all-solid-state lithium-sulfur batteries with high energy density (>2500 Wh kg-1) at a high current density of 5016 mA g-1. The present study opens up an unexplored research area in the field of solid electrolyte materials, contributing to the development of high-energy-density batteries.

Mucin O-glycans facilitate symbiosynthesis to maintain gut immune homeostasis.

BACKGROUND: The dysbiosis of gut microbiota has been implicated in the pathogenesis of inflammatory bowel diseases; however, the underlying mechanisms have not yet been elucidated. Heavily glycosylated mucin establishes a first-line barrier against pathogens and serves as a niche for microbial growth. METHODS: To elucidate relationships among dysbiosis, abnormal mucin utilisation, and microbial metabolic dysfunction, we analysed short-chain fatty acids (SCFAs) and mucin components in stool samples of 40 healthy subjects, 49 ulcerative colitis (UC) patients, and 44 Crohn's disease (CD) patients from Japan. FINDINGS: Levels of n-butyrate were significantly lower in stools of both CD and UC patients than in stools of healthy subjects. Correlation analysis identified seven bacterial species positively correlated with n-butyrate levels; the major n-butyrate producer, Faecalibacterium prausnitzii, was particularly underrepresented in CD patients, but not in UC patients. In UC patients, there were inverse correlations between mucin O-glycan levels and the production of SCFAs, such as n-butyrate, suggesting that mucin O-glycans serve as an endogenous fermentation substrate for n-butyrate production. Indeed, mucin-fed rodents exhibited enhanced n-butyrate production, leading to the expansion of RORgt+Treg cells and IgA-producing cells in colonic lamina propria. Microbial utilisation of mucin-associated O-glycans was significantly reduced in n-butyrate-deficient UC patients. INTERPRETATION: Mucin O-glycans facilitate symbiosynthesis of n-butyrate by gut microbiota. Abnormal mucin utilisation may lead to reduced n-butyrate production in UC patients. FUND: Japan Society for the Promotion of Science, Health Labour Sciences Research Grant, AMED-Crest, AMED, Yakult Foundation, Keio Gijuku Academic Development Funds, The Aashi Grass Foundation, and The Canon Foundation.

High-Throughput Investigation of a Lead-Free AlN-Based Piezoelectric Material, (Mg,Hf)xAl1-xN.

We conducted a high-throughput investigation of the fundamental properties of (Mg,Hf)xAl1-xN thin films (0 < x < 0.24) aiming for developing high-performance AlN-based piezoelectric materials. For the high-throughput investigation, we prepared composition-gradient (Mg,Hf)xAl1-xN films grown on a Si(100) substrate at 600 °C by cosputtering AlN and MgHf targets. To measure the properties of the various compositions at different positions within a single sample, we used characterization techniques with spatial resolution. X-ray diffraction (XRD) with a beam spot diameter of 1.0 mm verified that Mg and Hf had substituted into the Al sites and caused an elongation of the c-axis of AlN from 5.00 Å for x = 0 to 5.11 Å for x = 0.24. In addition, the uniaxial crystal orientation and high crystallinity required for piezoelectric materials to be used as application devices were confirmed. The piezoelectric response microscope indicated that this c-axis elongation increased the piezoelectric coefficient almost linearly from 1.48 pm/V for x = 0 to 5.19 pm/V for x = 0.24. The dielectric constants of (Mg,Hf)xAl1-xN were investigated using parallel plate capacitor structures with ∼0.07 mm2 electrodes and showed a slight increase by substitution. These results verified that (Mg,Hf)xAl1-xN is a promising material for piezoelectric-based application devices, especially for vibrational energy harvesters.

Self-Assembly Strategy for Fabricating Connected Graphene Nanoribbons.

We use self-assembly to fabricate and to connect precise graphene nanoribbons end to end. Combining scanning tunneling microscopy, Raman spectroscopy, and density functional theory, we characterize the chemical and electronic aspects of the interconnections between ribbons. We demonstrate how the substrate effects of our self-assembly can be exploited to fabricate graphene structures connected to desired electrodes.