Search

The search continues for nickel oxide-based materials with electronic properties similar to cuprate high-temperature superconductors 1-10 . The recent discovery of superconductivity in the doped infinite-layer nickelate NdNiO 2 (refs. 11,12 ) has strengthened these efforts. Here, we use X-ray spectroscopy and density functional theory to show that the electronic structure of LaNiO 2 and NdNiO 2 , while similar to the cuprates, includes significant distinctions. Unlike cuprates, the rare-earth spacer layer in the infinite-layer nickelate supports a weakly interacting three-dimensional 5d metallic state, which hybridizes with a quasi-two-dimensional, strongly correlated state with [Formula: see text] symmetry in the NiO 2 layers. Thus, the infinite-layer nickelate can be regarded as a sibling of the rare-earth intermetallics 13-15 , which are well known for heavy fermion behaviour, where the NiO 2 correlated layers play an analogous role to the 4f states in rare-earth heavy fermion compounds. This Kondo- or Anderson-lattice-like 'oxide-intermetallic' replaces the Mott insulator as the reference state from which superconductivity emerges upon doping.

Orally active hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors that stabilize HIF protein and stimulate the production of erythropoietin have been approved to treat renal anemia. Our previous report suggested that HIF-1α dependent fibrogenic mechanisms are operating at the early onset of renal fibrosis and its contribution declines with the progression in mouse unilateral ureteral obstruction (UUO) model. The aim of the study is to evaluate the renal fibrogenic potential of FG4592, a recently approved orally active HIF prolyl hydroxylase inhibitor in mouse UUO model. Male C57BL/6J mice orally given FG-4592 (12.5 mg/kg/day and 50 mg/kg/day) were subjected to UUO. Neither dose of FG-4592 affected renal fibrosis or macrophage infiltration. FG-4592 had no effects on increased mRNA of collagen I, collagen III or transforming growth factor-β1. At 3 days after UUO, higher dose of FG-4592 potentiated the increased mRNA expression of profibrogenic molecules, plasminogen activator inhibitor 1 (Pai-1) and connective tissue growth factor (Ctgf) but such potentiation disappeared at 7 days after UUO. It is suggested that FG-4592 used in the present study had little effects on renal fibrosis even though high dose of FG-4592 used in the present study transiently potentiated gene expression of Pai-1 and Ctgf in the UUO kidney., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2019 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

In inorganic-organic perovskites, the three-dimensional arrangement of the organic group results in more subtle balance of charge, spin and space, thereby providing an attractive route toward new multiferroics. Here we report the existing of multiple ferroic orderings in inorganic-organic layered perovskites with relative strong hydrogen bond ordering of the organic chains intra plane. In addition, the inter plane in perovskite is stacking via van der Waals force. However, such magnetoelectric coupling properties for this compound have not been reported since it is difficult to characterize the properties in single crystals since most of the hybrid perovskites are usually deliquescent and unstable when exposed to air. To deal with these problems, we synthesized a (CH 3 NH 3 ) 2 CuCl 4 single crystal by using a simple evaporation technique, and demonstrated ferroelectric, magnetic and magneto-electric properties of (CH 3 NH 3 ) 2 CuCl 4 . The internal hydrogen bonding of easily tunable organic unit combined with 3d transition-metal layers in such hybrid perovskites make (CH 3 NH 3 ) 2 CuCl 4 a multiferroic crystal with magnetoelectrical coupling and offer an new way to engineer multifunctional multiferroic.

Sapphirinid copepods, which are marine zooplankton, exhibit tunable structural colors originating from a layered structure of guanine crystal plates. In the present study, the coloring portion of adult male of a sapphirinid copepod, Sapphirina nigromaculata, under the dorsal body surface was characterized to clarify the regulation and actuation mechanism of the layered guanine crystals for spectral control. The coloring portions are separated into small domains 70-100 µm wide consisting of an ordered array of stacked hexagonal plates ~1.5 µm wide and ~80 nm thick. We found the presence of chitin-based honeycomb frameworks that are composed of flat compartments regulating the guanine crystal plates. The structural color is deduced to be tuned from blue to achromatic via yellow and purple by changing the interplate distance according to vital observation and optical simulation using a photonic array model. The framework structures are essential for the organization and actuation of the particular photonic arrays for the exhibition of the tunable structural color.

The interaction of plasmonic nanoparticles with a dielectric platform gives rise to unique optical behaviors and this can be maneuvered to improve the plasmonic/SERS performances of a substrate. Herein, dielectric modified plasmonic-paper SERS substrate is developed by assembling Ag@SiO 2 nanocubes on Fe-TiO 2 nanosheets (NS) modified paper. The Fe-TiO 2 NS being visible light responsive significantly alters the optical property of the paper and serves as a dielectric underlay for the Ag nanocubes. Hence, the incident light reflected back from the dielectric nanosheets couples with the scattered light from the Ag nanocubes leading to spatially enhanced electromagnetic field improving the SERS enhancement. The prepared dielectric modified plasmonic-paper has an average enhancement factor (EF) of 1.49 × 10 7 using R6G as a probe molecule. This value is superior to unmodified plasmonic-paper highlighting the coupling effect of the dielectric nanosheets. The substrate shows robust detection performance for thiabendazole and achieves a limit of detection (LOD) of 19 μg/L, which is 4-fold more sensitive than unmodified plasmonic paper. Direct swabbing test of thiabendazole sprayed apple fruit shows a discernible Raman signal down to 15 ppb indicating the utility of the substrate for point-of-need applications in food safety., (Copyright © 2019. Published by Elsevier B.V.)

Bordetella pertussis, B. parapertussis, and B. bronchiseptica cause respiratory infections in mammals, including humans, and are generally cultivated on Bordet-Gengou (BG) agar plates in laboratories. The medium requires animal blood as a supplement for better bacterial growth. However, using blood is problematic, as its constant supply is occasionally difficult because of the limited shelf-life. This study proposes modified BG agar plates supplemented with bovine serum albumin and fetal bovine serum as a simple and convenient medium that confers sufficient growth of bordetellae., (© 2019 The Societies and John Wiley & Sons Australia, Ltd.)

Mycobacterium tuberculosis ( M. tuberculosis ) produces a diverse range of antigenic proteins in its dormant phase. The cytokine profiles of CD4 + T cell responses, especially subsets other than Th1 type (non-Th1 type), against these latency-associated M. tuberculosis antigens such as α-crystallin (Acr), heparin-binding hemagglutinin (HBHA), and mycobacterial DNA-binding protein 1 (MDP-1) remain elusive in relation to the clinical stage of M. tuberculosis infection. In the present study, peripheral blood mononuclear cells (PBMCs) collected from different stages of M. tuberculosis -infected cases and control PBMCs were stimulated with these antigens and ESAT-6/CFP-10. Cytokine profiles of CD4 + T cells were evaluated by intracellular cytokine staining using multicolor flow cytometry. Our results demonstrate that Th1 cytokine responses were predominant after TB onset independent of the type of antigen stimulation. On the contrary, non-Th1 cytokine responses were preferentially induced by latency-associated M. tuberculosis antigens, specifically IL-10 response against Acr in latent M. tuberculosis infection. From these results, we surmise a shift in the CD4 + T cell response from mixed non-Th1 to Th1 dominant type during TB progression., (Copyright © 2019 Yamashita, Oe, Kawakami, Osada-Oka, Ozeki, Terahara, Yasuda, Edwards, Tanaka, Tsunetsugu-Yokota, Matsumoto and Ariyoshi.)

Macrophages are major components of tuberculosis (TB) granulomas and are responsible for host defenses against the intracellular pathogen, Mycobacterium tuberculosis. We herein showed the strong expression of hypoxia-inducible factor-1α (HIF-1α) in TB granulomas and more rapid death of HIF-1α-conditional knockout mice than wild-type (WT) mice after M. tuberculosis infection. Although interferon-γ (IFN-γ) is a critical host-protective cytokine against intracellular pathogens, HIF-1-deficient macrophages permitted M. tuberculosis growth even after activation with IFN-γ. These results prompted us to investigate the role of HIF-1α in host defenses against infection. We found that the expression of lactate dehydrogenase-A (LDH-A) was controlled by HIF-1α in M. tuberculosis-infected macrophages IFN-γ independently. LDH-A is an enzyme that converts pyruvate to lactate and we found that the intracellular level of pyruvate in HIF-1α-deficient bone marrow-derived macrophages (BMDMs) was significantly higher than in WT BMDMs. Intracellular bacillus replication was enhanced by an increase in intracellular pyruvate concentrations, which were decreased by LDH-A. Mycobacteria in phagosomes took up exogenous pyruvate more efficiently than glucose, and used it as the feasible carbon source for intracellular growth. These results demonstrate that HIF-1α prevents the hijacking of pyruvate in macrophages, making it a fundamental host-protective mechanism against M. tuberculosis., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Japanese Society for Immunology.)

Heterostructures of two-dimensional (2D) atomic crystals provide fascinating molecular-scale design elements for emergent physical phenomena and functional materials, as integrating distinct monolayers into vertical heterostructures can afford coupling between disparate properties. However, the available examples have been limited to either van der Waals (vdW) or electrostatic (ES) heterostructures that are solely composed of noncharged and charged monolayers, respectively. Here, we propose a "vdW-ES heterostructure" chemical design in which charge-neutral and charged monolayer-building blocks with highly disparate chemical and physical properties are conjugated vertically through asymmetrically charged interfaces. We demonstrate vdW-ES heteroassembly of semiconducting MoS 2 and dielectric Ca 2 Nb 3 O 10 - (CNO) monolayers using an amphipathic molecular starch, resulting in the emergence of trion luminescence observed at the lowest energy among MoS 2 -related materials, probably due to interfacial confinement effects given by vdW-ES dual interactions. In addition, interface engineering leads to tailored exciton of the vdW/ES heterostructures owing to the pronounced dielectric proximity effects, bringing an intriguing interlayer chemistry to modify 2D materials. Furthermore, the current approach was successfully extended to create a graphene/CNO heterostructure, which verifies the versatility of the preparative method.

The neuropeptide control of bivalve reproduction with particular reference to gonadotropin-releasing hormone (invGnRH) is a frontier yet to be investigated. Bivalves are unique because they have two forms of the invGnRH peptide; however, there has been no functional characterization of the peptide-receptor pair. Therefore, the identification of a cognate receptor is a preliminary step toward exploring the biological roles of invGnRHs in bivalves. In this study, we functionally characterize an invGnRH receptor (invGnRHR) of a bivalve, the Yesso scallop Mizuhopecten yessoensis. In the receptor assay, HEK293 cells were transfected to transiently express the M. yessoensis invGnRHR (my-invGnRHR), which was found to be localized on the plasma membrane, confirming that my-invGnRHR, similar to other G-protein-coupled receptors, functions as a membrane receptor. Using both forms of invGnRH as ligands in a function-receptor assay, my-invGnRH11aa-NH 2 stimulated intracellular Ca 2+ mobilization but not cyclic AMP production, whereas my-invGnRH12aa-OH did not induce increase in Ca 2+ levels. Therefore, we concluded that my-invGnRHR is an endogenous receptor specific to my-invGnRH11aa-NH 2 which is hypothesized to be the mature peptide. To the best of our knowledge, this is the first study reporting the functional characterization of a bivalve invGnRHR., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Fibroblast growth factor receptor (FGFR) 2 is overexpressed in several tumor types, including triple-negative breast cancer and gastric cancer, both of which have a high unmet medical need. Aprutumab ixadotin (BAY 1187982) is the first antibody-drug conjugate (ADC) to target FGFR2 and the first to use a novel auristatin-based payload., Objective: This first-in-human trial was conducted to determine the safety, tolerability, and maximum tolerated dose (MTD) of aprutumab ixadotin in patients with advanced solid tumors from cancer indications known to be FGFR2-positive., Patients and Methods: In this open-label, multicenter, phase I dose-escalation trial (NCT02368951), patients with advanced solid tumors received escalating doses of aprutumab ixadotin (starting at 0.1 mg/kg body weight), administered intravenously on day 1 of every 21-day cycle. Primary endpoints included safety, tolerability, and the MTD of aprutumab ixadotin; secondary endpoints were pharmacokinetic evaluation and tumor response to aprutumab ixadotin., Results: Twenty patients received aprutumab ixadotin across five cohorts, at doses of 0.1-1.3 mg/kg. The most common grade ≥ 3 drug-related adverse events were anemia, aspartate aminotransferase increase, proteinuria, and thrombocytopenia. Dose-limiting toxicities were thrombocytopenia, proteinuria, and corneal epithelial microcysts, and were only seen in the two highest dosing cohorts. The MTD was determined to be 0.2 mg/kg due to lack of quantitative data following discontinuations at 0.4 and 0.8 mg/kg doses. One patient had stable disease; no responses were reported., Conclusions: Aprutumab ixadotin was poorly tolerated, with an MTD found to be below the therapeutic threshold estimated preclinically; therefore, the trial was terminated early. CLINICALTRIALS., Gov Identifier: NCT02368951.

We determined the primary structures of jacalin-related lectins termed PPL3s (PPL3A, 3B, and 3C, which are dimers consisting of sequence variants α + α, α + β, β + β, respectively) and PPL4, which is heterodimer consisting of α + β subunits, isolated from mantle secretory fluid of Pteria penguin (Mabe) pearl shell. Their carbohydrate-binding properties were analyzed, in addition to that of PPL2A, which was previously reported as a matrix protein. PPL3s and PPL4 shared only 35-50% homology to PPL2A, respectively; they exhibited significantly different carbohydrate-binding specificities based on the multiple glycan binding profiling data sets from frontal affinity chromatography analysis. The carbohydrate-binding specificity of PPL3s was similar to that of PPL2A, except only for Man 3 Fuc 1 Xyl 1 GlcNAc 2 oligosaccharide, while PPL4 showed different carbohydrate-binding specificity compared with PPL2A and PPL3s. PPL2A and PPL3s mainly recognize agalactosylated- and galactosylated-type glycans. On the other hand, PPL4 binds to high-mannose-and hybrid-type N-linked glycans but not agalactosylated- and galactosylated-type glycans.

Soluble forms of platelet membrane proteins are released upon platelet activation. We previously reported that soluble C-type lectin-like receptor 2 (sCLEC-2) is released as a shed fragment (Shed CLEC-2) or as a whole molecule associated with platelet microparticles (MP-CLEC-2). In contrast, soluble glycoprotein VI (sGPVI) is released as a shed fragment (Shed GPVI), but not as a microparticle-associated form (MP-GPVI). However, mechanism of sCLEC-2 generation or plasma sCLEC-2 has not been fully elucidated. Experiments using metalloproteinase inhibitors/stimulators revealed that ADAM10/17 induce GPVI shedding, but not CLEC-2 shedding, and that shed CLEC-2 was partially generated by MMP-2. Although MP-GPVI was not generated, it was generated in the presence of the ADAM10 inhibitor. Moreover, antibodies against the cytoplasmic or extracellular domain of GPVI revealed the presence of the GPVI cytoplasmic domain, but not the extracellular domain, in the microparticles. These findings suggest that most of the GPVI on microparticles are induced to shed by ADAM10; MP-GPVI is thus undetected. Plasma sCLEC-2 level was 1/32 of plasma sGPVI level in normal subjects, but both soluble proteins significantly increased in plasma of patients with acute coronary syndrome. Thus, sCLEC-2 and sGPVI are released by different mechanisms and released in vivo upon platelet activation.

The non-catalytic conversion of chitin into N-acetyl-ᴅ-glucosamine (GlcNAc) derivatives such as 2-acetamido-2,3-dideoxy-ᴅ-erythro-hex-2-enofuranose (Chromogen I) was investigated in high-temperature water at 290-390 °C and 25 MPa with a reaction time of 0-180 min. High-temperature water treatment is a promising method for chitin conversion as it does not require the use of any additional organic solvents or ionic liquids. A semi-batch reactor was developed to control the reaction temperature and time. It was found that the chitin powder could be converted into a water-soluble fraction in ~90% yield, with Chromogen I being obtained in a maximum yield of 2.6%. Furthermore, a kinetic model was developed to estimate the reaction rate for the conversion of the chitin powder to the water-soluble fraction., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Vapor transportation is the core process in growing transition-metal dichalcogenides (TMDCs) by chemical vapor deposition (CVD). One inevitable problem is the spatial inhomogeneity of vapors. The non-stoichiometric supply of transition-metal precursors and chalcogens leads to poor control in the products' location, morphology, crystallinity, uniformity and batch to batch reproducibility. The vapor-liquid-solid (VLS) growth method often involves molten precursors (e.g., non-volatile Na2MoO4) at growth temperatures higher than their melting points. The liquid Na2MoO4 can precipitate out solid MoS2 monolayers when saturated with sulfur vapor. Taking advantage of the VLS growth, we attained three kinds of important achievements: (i) a 4-inch-wafer-scale uniform growth of MoS2 flakes on SiO2/Si substrates, (ii) a 2-inch-wafer-scale growth of continuous MoS2 film with the grain size exceeding 100 μm on sapphire substrates, and (iii) a patterned (site-controlled) growth of MoS2 flakes and films. We clarified that the VLS growth thus paves a new way for the high-efficient and scalable synthesis of two-dimensional TMDC monolayers.

This study was conducted to evaluate and compare the economic benefits of different embryo sexing methods, based on the cost per female dairy calf produced. Female calves were produced from four kinds of female embryos: (1) those collected from superstimulated donors at 7-8 days after artificial insemination (AI) with X-sorted semen; (2) those sex-determined by loop-mediated isothermal amplification assay of a biopsy sample of embryos collected from superstimulated donors after AI with conventional unsorted semen; (3) those obtained by invitro embryo production (IVEP), using X-sorted semen and in vitro-matured oocytes collected from donors by ovum pick-up (OPU); and (4) those obtained by IVEP, using X-sorted semen and oocytes collected by OPU after dominant follicle ablation and follicle growth stimulation of the donors. The respective productivities of female calves per technical service and the total production cost per female calf of each sexing method were compared. The production cost per female calf (66,537 JPY), as calculated from the number of female calves per service (1.30), pregnancy rate of transfer (42.9%), rate of female calves obtained (92.9%), and total cost of the method (56,643 JPY plus embryo transfer fee), was less for IVEP with X-sorted semen and follicular growth-stimulated (FGS) oocytes than for the other groups (P < 0.05). The results demonstrate that embryo production with X-sorted semen and FGS oocytes provides a more efficient method for producing female calves than the other embryo sexing methods.

The discovery of unconventional superconductivity in (La,Ba) 2 CuO 4 (ref. 1 ) has motivated the study of compounds with similar crystal and electronic structure, with the aim of finding additional superconductors and understanding the origins of copper oxide superconductivity. Isostructural examples include bulk superconducting Sr 2 RuO 4 (ref. 2 ) and surface-electron-doped Sr 2 IrO 4 , which exhibits spectroscopic signatures consistent with a superconducting gap 3,4 , although a zero-resistance state has not yet been observed. This approach has also led to the theoretical investigation of nickelates 5,6 , as well as thin-film heterostructures designed to host superconductivity. One such structure is the LaAlO 3 /LaNiO 3 superlattice 7-9 , which has been recently proposed for the creation of an artificially layered nickelate heterostructure with a singly occupied [Formula: see text] band. The absence of superconductivity observed in previous related experiments has been attributed, at least in part, to incomplete polarization of the e g orbitals 10 . Here we report the observation of superconductivity in an infinite-layer nickelate that is isostructural to infinite-layer copper oxides 11-13 . Using soft-chemistry topotactic reduction 14-20 , NdNiO 2 and Nd 0.8 Sr 0.2 NiO 2 single-crystal thin films are synthesized by reducing the perovskite precursor phase. Whereas NdNiO 2 exhibits a resistive upturn at low temperature, measurements of the resistivity, critical current density and magnetic-field response of Nd 0.8 Sr 0.2 NiO 2 indicate a superconducting transition temperature of about 9 to 15 kelvin. Because this compound is a member of a series of reduced layered nickelate crystal structures 21-23 , these results suggest the possibility of a family of nickelate superconductors analogous to copper oxides 24 and pnictides 25 .

The inherent instability of UV-induced degradation in TiO 2 -based perovskite solar cells was largely improved by replacing the anatase-phase compact TiO 2 layer with an atomic sheet transport layer (ASTL) of two-dimensional (2D) Ti 1-δ O 2 . The vital role of microscopic carrier dynamics that govern the UV stability of perovskite solar cells was comprehensively examined in this work by performing time-resolved pump-probe spectroscopy. In conventional perovskite solar cells, the presence of a UV-active oxygen vacancy in compact TiO 2 prohibits current generation by heavily trapping electrons after UV degradation. Conversely, the dominant vacancy type in the 2D Ti 1-δ O 2 ASTL is a titanium vacancy, which is a shallow acceptor and is not UV-sensitive. Therefore, it significantly suppresses carrier recombination and extends UV stability in perovskite solar cells with a 2D Ti 1-δ O 2 ASTL. Other carrier dynamics, such as electron diffusion, electron injection, and hot hole transfer processes, were found to be less affected by UV irradiation. Quantitative pump-probe data clearly show a correlation between the carrier dynamics and UV aging of perovskite solar cells, thus providing a profound insight into the factors driving UV-induced degradation in perovskite solar cells and the origin of its performance.

The objective of the present study was to analyze the phenotypic stability of sex after sex differentiation in the Yesso scallop, which is a gonochoristic species that has been described as protandrous. So far, no study has investigated in detail the sexual fate of the scallop after completion of sex differentiation, although bivalve species often show annual sex change. In the present study, we performed a tracking experiment to analyze the phenotypic stability of sex in scallops between one and two years of age. We also conducted molecular marker analyses to describe sex differentiation and gonad development. The results of the tracking experiment revealed that all scallops maintained their initial sex phenotype, as identified in the last reproductive period. Using molecular analyses, we characterized my-dmrt2 and my-foxl2 as sex identification markers for the testis and ovary, respectively. We conclude by proposing that the Yesso scallop is a sex-stable bivalve after its initial sex differentiation and that it maintains a sex-stable maturation system throughout its life. The sex-specific molecular markers identified in this study are useful tools to assess the reproductive status of the Yesso scallop., Competing Interests: The authors declare no conflict of interest.

The purpose of this study was to evaluate the solubilities and physicochemical properties of solid dispersions of daidzein (DDZ) and genistein (GST) (the major isoflavones in soybeans) in γ-cyclodextrin (γCD). Dispersions were prepared in distilled water using a three-dimensional ball mill (3DGMw). Phase solubility diagrams confirmed that DDZ/γCD and GST/γCD formed A L type inclusion complexes with a molar ratio of 1:1. A new peak due to inclusion complexes was observed in the results of powder X-ray diffraction (3DGMw(DDZ/γCD = 1:1) and 3DGMw(GST/γCD = 1:1)). Dissolution tests using distilled water found that solubilities of 3DGMw(DDZ/γCD = 1:1) and 3DGMw(GST/γCD = 1:1) were approximately 37- and 51-fold higher, respectively, than the solubilities of pure DDZ and GST. These observations are expected to expand the usefulness of cogrinding of DDZ or GST with γCD using a three-dimensional ball mill., Competing Interests: The authors declare no competing financial interest.

Intestinal wound healing depends on the precise balance of restitution, proliferation, and differentiation of intestinal epithelial cells (IECs). In a previous study, we revealed that IEC proliferation was suppressed under histidine deficiency. However, the role of histidine in cell restitution is poorly understood. Meanwhile, addition of arginine to basal medium enhanced IEC restitution after wounding. However, there are no reports on whether histidine or arginine deficiency influences IEC restitution. We examined the roles of histidine and arginine in IEC restitution using the rat intestinal epithelial cell-6 (IEC-6) cell line. In the present study, the cell restitution in medium lacking histidine (ΔHis) or arginine (ΔArg) was most greatly decreased among media lacking each of the 20 intravital amino acids, compared with that in medium containing all 20 intravital amino acids (Full). TGF-β 1 is a known repair factor for cell restitution. The TGF-β 1 extracellular concentration and Tgf-β 1 mRNA level were decreased in ΔHis or ΔArg. Supplementation of 10 µM histidine to ΔHis or 50 µM arginine to ΔArg recovered the decreases in both cell restitution and TGF-β 1 extracellular concentration. Phosphorylation of Smad2, a signaling molecule for the TGF-β pathway, was decreased in ΔHis or ΔArg. Additionally, the phosphorylation of mammalian target of rapamycin, p70 ribosomal protein S6 kinase and extracellular signal-regulated kinase were decreased in ΔHis or ΔArg. The present findings suggested that deletion of histidine or arginine led to a decrease in IEC restitution through a decrease in TGF-β 1 . We revealed that histidine and arginine play important roles in IEC restitution., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Understanding how structural properties affect the oxygen evolution reaction (OER) of a catalyst can reveal important information not only on the catalytic mechanism but also on the general design strategy of OER catalysts. We report a variation of ∼0.15 V in the overpotential of the recently discovered IrO x /SrIrO 3 OER catalysts, which directly correlates with the structural parameters of the as-synthesized SrIrO 3 epitaxial films. This variation is caused by both extrinsic area enhancement and intrinsic electronic structure modification driven by defect formation. These correlations not only indicate that microscopic film defects play an important role in the activity of the IrO x /SrIrO 3 catalyst but also provide readily accessible parameters predictive of the activity post-transformation to IrO x /SrIrO 3 . Establishing strong associations between the catalytic activity and key structural and electronic parameters, rather than synthetic variables, provides important guidance to control and study these complex catalysts independent of the synthetic technique.

Artificial insemination using sex-sorted semen is employed to efficiently increase the number of female dairy calves born. Previous studies have determined that using sex-sorted semen is beneficial to improve the management, but the mechanism by which it increases cattle numbers through objective indices of breeding remains unclear. This study focused on a Brown Swiss cattle herd in which frozen female sex-sorted semen was systematically employed to increase the number of cattle. We analyzed the correlation between the increase in the number of cattle and the screening accuracy of sex-sorted semen, measuring indices such as pregnancy rate and birth rate of female calves. Study revealed that: (1) production cost for female calves is influenced by the pregnancy rate, rate of female calves, and using sex-sorted semen is less expensive than using nonsorted semen; (2) improvements in screening accuracy nearly doubled the number of cows and tripled the number of heifers in 5 years; and (3) use of sex-sorted semen improved milk quality. The pregnancy rate was lower when sex-sorted semen was used, but the birth rate of heifers was improved. Results suggest that artificial insemination using sex-sorted semen is beneficial because it economically produces offspring to increase the herd., (© 2019 The Authors. Animal Science Journal published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Animal Science.)

In this study, chitin nanofiber dispersions prepared in neutral and acidic pH conditions were lyophilized to produce aerogels. The effects of the freezing speed of the nanofiber dispersions and the dispersibility of the chitin nanofiber were studied. The characteristics of the aerogels were studied using scanning electron microscopy, relative surface area measurements, and compression tests. The repulsion forces of the chitin nanofiber in acidic conditions were effective in the formation of a more uniform microstructure during water solidification, resulting in aerogels with a high mechanical strength. The aerogel made from the chitin nanofiber dispersion prepared in neutral conditions was influenced by ice crystal growth during freezing, resulting in a nonuniform structure. In contrast, the surface area of the aerogel in neutral conditions interestingly remained unchanged compared to that of the original powder, which was due to the morphological transformation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Oxide ion-conducting porous films were produced on a substrate by evaporation-induced self-assembly of rare earth-doped CeO2 (REDC) nanocubes 4-5 nm in size and subsequent mild calcination at 400 °C. Mesocrystalline structures comprising iso-oriented REDC nanocubes were formed by ordered assembly based on strict attachment of their {100} faces. Enhanced oxide-ion conductivities in a temperature range of 250-350 °C were observed on the mesocrystalline films consisting of Sm-doped CeO2 (SDC) nanocubes. The specific electrical properties of the mesocrystalline films are ascribed to improved surface-ion conduction due to a large specific surface area and a high crystallographic connectivity of SDC nanocubes.

One-third of the world's humans has latent tuberculosis infection (LTBI), representing a large pool of potentially active TB. Recent LTBI carries a higher risk of disease progression than remote LTBI. Recent studies suggest important roles of antibodies in TB pathology, prompting us to investigate serum antibody profiles in a cohort with LTBI. In this single-center prospective observational study, we analyzed IgG-antibody concentrations against five major Mycobacterium tuberculosis (Mtb) antigens (including 6 kDa early secretory antigenic target (ESAT6), CFP10, and antigen 85A, which are expressed mainly in the growth phase; and mycobacterial DNA-binding protein 1 (MDP1) and alpha-crystallin like protein (Acr), which are expressed in the dormant phases) in individuals with recent (n=13) or remote (n=12) LTBI, no Mtb infection (n=19), or active TB (n=15). Antibody titers against ESAT6 and MDP1 were significantly higher in individuals with recent LTBI than in those with no Mtb infection or remote LTBI. All pairwise antibody titers against these five major antigens were significantly correlated throughout the stages of Mtb infection. Five individuals with recent LTBI had significantly higher antibody titers against ESAT6 (P = 0.03), Ag85A (P = 0.048), Acr (P = 0.057), and MDP1 (P = 0.0001) than in individuals with remote LTBI; they were also outside the normal range (+2 SDs). One of these individuals was diagnosed with active pulmonary TB at 18-month follow-up examination. These findings indicated that concentrations of antibodies against both multiplying and dormant Mtb are higher in recent LTBI and that individuals with markedly higher antibody titers may be appropriate candidates for prophylactic therapy., (© 2019 The Societies and John Wiley & Sons Australia, Ltd.)

Background: Post-extubation dysphagia reportedly occurs in 3%-60% of patients and is independently associated with poor patient outcomes., Aim: The aim of this study was to investigate the frequency of post-extubation dysphagia, as diagnosed using our novel nurse-performed swallowing screening protocol, and to evaluate patient outcomes, including the frequency of discharge home, the length of the intensive care unit and hospital stays, the frequency of hospital-acquired pneumonia and death in the intensive care unit and hospital., Design: This was a prospective cohort study., Methods: This study was conducted in a mixed intensive care unit in a critical care hospital in Japan. Between October 2016 and September 2017, the swallowing functions of 216 patients were assessed using our novel screening protocol. To investigate the correlation between dysphagia and patient outcomes, we compared a dysphagia group with a no dysphagia group., Results: Twenty-five patients (11·6%) were diagnosed with dysphagia. The frequency of discharge home, which was the primary outcome, was significantly lower in the patients with dysphagia (60% versus 87·4%, P = 0·002). Dysphagia was also correlated with longer hospital stay and higher mortality. A binomial logistic regression analysis, including the variables of dysphagia, Acute Physiology and Chronic Health Evaluation II score and duration of ventilator use, showed that dysphagia was an independent risk factor for a lower incidence of discharge home., Conclusion: Among patients admitted to a mixed intensive care unit, post-extubation dysphagia was correlated with a poor prognosis., Relevance to Clinical Practice: The current study emphasizes the poor prognosis of patients with dysphagia after extubation. Dysphagia developed in more than 1 in 10 patients post-extubation; therefore, monitoring for a swallowing disorder is crucial in daily nursing in the intensive care unit., (© 2018 British Association of Critical Care Nurses.)

Dipeptidyl peptidase-4 (DPP-4) inhibitors not only improve impaired glucose tolerance in diabetes, but also have pleiotropic extra-pancreatic effects such as preconditioning effect for myocardial ischemia-reperfusion injury. Here, we investigated the anti-remodeling effects of linagliptin, a DPP-4 inhibitor, by use of DPP-4-deficient rats. After the induction of myocardial infarction (MI), Fischer 344 rats with inactivating mutation of DPP-4 were orally administrated with a DPP-4 inhibitor, linagliptin (5 mg kg -1 ·day -1 ), or vehicle in drinking water for 4 weeks. Linagliptin did not affect hemodynamic status, body weight, and infarct size. In echocardiography, linagliptin tended to improve left ventricular (LV) systolic function, and significantly improved LV diastolic function, surprisingly. Interstitial fibrosis in marginal region and macrophage infiltration were significantly lower in the linagliptin group than those in the vehicle group. Fibrosis-related gene expressions, such as collagen I and transforming growth factor-β1 (TGF-β1), and inflammation-related expressions, such as macrophage chemotactic protein 1 and matrix metalloproteinase-2 (MMP-2), were significantly suppressed in marginal area of the linagliptin-treated rats compared with the vehicle rats. The TGF-β1 and MMP-2 protein levels were attenuated by linagliptin in DPP-4-deficient cardiac fibroblasts. Linagliptin can attenuate MI-induced cardiac remodeling via a DPP-4-independent pathway., (Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Sex steroids are crucial for controlling gametogenesis and germ cell maturation in vertebrates. It has been proposed that Yesso scallop (Mizuhopecten yessoensis) has the same sex steroids as those animals, but the scallop biosynthetic pathway is unclear. In this study, we characterized several steroidogenesis-related genes in M. yessoensis and proposed a putative biosynthetic pathway for sex steroids that is similar to that of vertebrates. Specifically, we identified several steroidogenesis-related gene sequences that encode steroid metabolizing enzymes: StAR-related lipid transfer (START) protein, 17α-hydroxylase, 17,20-lyase (cyp17a), 17β-hydroxysteroid dehydrogenase (hsd17b), and 3β-hydroxysteroid dehydrogenase (hsd3b). We sampled adult scallops throughout their reproductive phase to compare their degree of maturation with their intensity of mRNA expression. Semi-quantitative RT-PCR analysis revealed a ubiquitous expression of transcripts for steroid metabolizing enzymes (i.e., star, cyp17a, hsd17b, and hsd3b) in peripheral and gonadal tissues. Real-time PCR analysis revealed a high level of expression of star3 and cyp17a genes in gonadal tissues at the early stage of cell differentiation in scallops. Interestingly, mRNA expression of hsd3b and hsd17b genes showed a synchronous pattern related to degree of gonad maturity. These results indicate that both hsd3b and hsd17b genes are likely involved in steroidogenesis in scallops. We therefore believe that these steroid-metabolizing enzymes allow scallops to endogenously produce sex steroids to regulate reproductive events., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

New drugs have significantly improved the survival of patients with multiple myeloma (MM), but the prognosis of MM patients with high-risk cytogenetic changes such as t(4; 14), t(14; 16) or del17p remains very poor. A natural product, komaroviquinone (KQN), was originally isolated from the perennial semi-shrub Dracocephalum komarovi and has anti-protozoal activity against Trypanosoma cruzi, the organism causing Chagas' disease. Here we demonstrate that a novel KQN-derivative, GTN024, has an anti-MM effect both in vitro and in vivo. GTN024 induced the apoptosis of MM cell lines including those with high-risk cytogenetic changes. GTN024 produced reactive oxygen species (ROS) and increased phosphorylated eIF2α. The ROS production and subsequent endoplasmic reticulum (ER) stress are thought to play a key role in GTN024-induced apoptosis, as the apoptosis was completely abrogated by anti-oxidant treatment. In a mouse xenograft model, an intraperitoneal injection of 20 mg/kg of GTN024 significantly delayed tumor growth. Hematological toxicity and systemic toxicity as indicated by weight loss were not observed. These results suggest that the novel KQN-derivative GTN024 could become a candidate drug for treating high-risk MM., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In our previous work, we have shown that "electrostatic forces", when generated anisotropically in aqueous media by 2D electrolytes upon cofacial orientation, enable the formation of a hydrogel with an anisotropic parameter, as defined by the ratio of elastic moduli E ⊥ /E ∥ , of 3.0. Herein, we successfully developed the design strategy for a hydrogel with an anisotropic parameter of no less than 85. This value is not only 28 times greater than that of our previous anisotropic hydrogel but also 6 times larger than the current champion record in synthetic hydrogels (E ⊥ /E ∥ ∼15). Firstly, we simply lowered ionic contaminants in the hydrogel and were able to enhance the anisotropic parameter from 3.0 to 18. Then, we chose a supporting polymer network allowing the hydrogel to carry a higher interior permittivity. Consequently, the anisotropic parameter was further enhanced from 18 to 85. Owing to the enhanced mechanical anisotropy, our new hydrogel displayed a superb ability of seismic isolation., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The platelet activation receptor C-type lectin-like receptor 2 (CLEC-2) interacts with podoplanin on the surface of certain types of tumor cells, and this interaction facilitates tumor metastasis. CLEC-2 is also involved in thrombus formation and its stabilization. Because CLEC-2-depleted mice are protected from experimental lung metastasis and thrombus formation and do not show increased bleeding time, CLEC-2 may serve as a good target for antimetastatic or antithrombotic drugs. We screened 6770 compounds for their capability to inhibit CLEC-2-podoplanin binding using an enzyme-linked immunosorbent assay. In the first screening round, 63 compounds were identified and further evaluated by flow cytometry using CLEC-2-expressing cells. We identified protoporphyrin IX (H2-PP) as the most potent inhibitor and modified its hematoporphyrin moiety to be complexed with cobalt (cobalt hematoporphyrin [Co-HP]), which resulted in an inhibitory potency much stronger than that of H2-PP. Surface plasmon resonance analysis and molecular docking study showed that Co-HP binds directly to CLEC-2 at N120, N210, and K211, previously unknown podoplanin-binding sites; this binding was confirmed by analysis of CLEC-2 mutants with alterations in N120 and/or K211. Co-HP at a concentration of 1.53 μM inhibited platelet aggregation mediated through CLEC-2, but not that mediated through other receptors. IV administration of Co-HP to mice significantly inhibited hematogenous metastasis of podoplanin-expressing B16F10 cells to the lung as well as in vivo arterial and venous thrombosis, without a significant increase in tail-bleeding time. Thus, Co-HP may be a promising molecule for antimetastatic and antiplatelet treatment that does not cause bleeding tendency., (© 2018 by The American Society of Hematology.)

Dynamic viscoelasticities were measured for chitin nanofiber (ChNF) dispersions prepared with various concentrations, disintegration times, acidities, and crystalline structures. The 0.05w/v% dispersions of pH neutral ChNFs continuously exhibited elastic behavior. The 0.05w/v% dispersions of acidified ChNFs, on the other hand, transitioned from a colloidal dispersion to a critical gel and then exhibited elastic behavior with increasing ChNF concentration. A double-logarithmic chart of the concentration vs. the storage modulus was prepared and indicated the fractal dimension and the nanostructure in the dispersion. The results determined that the neutral α- and β-ChNFs were dispersed but showed some remaining aggregations and that the acidified β-ChNFs were completely individualized. In addition, the α-chitin steadily disintegrated with increasing disintegration time, and the aspect ratio of the β-chitin decreased as a result of the exscessive disintegration. The storage moduli of the ChNFs were greater than those of chitin solutions, nanorods, and nanowhiskers with the same solids concentrations., (Copyright © 2017. Published by Elsevier B.V.)

Single-phase materials that combine electric polarization and magnetization are promising for applications in multifunctional sensors, information storage, spintronic devices, etc. Following the idea of a percolating network of magnetic ions (e.g., Fe) with strong superexchange interactions within a structural scaffold with a polar lattice, a solid solution thin film with perovskite structure at a morphotropic phase boundary with a high level of Fe atoms on the B site of perovskite structure is deposited to combine both ferroelectric and ferromagnetic ordering at room temperature with magnetoelectric coupling. In this work, a 0.85BiTi 0.1 Fe 0.8 Mg 0.1 O 3 -0.15CaTiO 3 thin film has been deposited by pulsed laser deposition (PLD). Both the ferroelectricity and the magnetism were characterized at room temperature. Large polarization and a large piezoelectric effective coefficient d 33 were obtained. Multifield coupling of the thin film has been characterized by scanning force microscopy. Ferroelectric domains and magnetic domains could be switched by magnetic field ( H), electric field ( E), mechanical force ( F), and, indicating that complex cross-coupling exists among the electric polarization, magnetic ordering and elastic deformation in 0.85BiTi 0.1 F e0.8 Mg 0.1 O 3 -0.15CaTiO 3 thin film at room temperature. This work also shows the possibility of writing information with electric field, magnetic field, and mechanical force and then reading data by magnetic field. We expect that this work will benefit information applications.

Chemical vapour deposition of two-dimensional materials typically involves the conversion of vapour precursors to solid products in a vapour-solid-solid mode. Here, we report the vapour-liquid-solid growth of monolayer MoS 2 , yielding highly crystalline ribbons with a width of few tens to thousands of nanometres. This vapour-liquid-solid growth is triggered by the reaction between MoO 3 and NaCl, which results in the formation of molten Na-Mo-O droplets. These droplets mediate the growth of MoS 2 ribbons in the 'crawling mode' when saturated with sulfur. The locally well-defined orientations of the ribbons reveal the regular horizontal motion of the droplets during growth. Using atomic-resolution scanning transmission electron microscopy and second harmonic generation microscopy, we show that the ribbons are grown homoepitaxially on monolayer MoS 2 with predominantly 2H- or 3R-type stacking. Our findings highlight the prospects for the controlled growth of atomically thin nanostructure arrays for nanoelectronic devices and the development of unique mixed-dimensional structures.

We prepared a self-sustaining hydrogel from 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-oxidized cellulose nanofibers (TOCNs) via hydrothermal treatment at 160 °C. The self-sustaining hydrogels could be obtained at less than 1 wt % TOCNs without any additives. Brownish hydrogels obtained after the hydrothermal treatment could be rendered transparent by immersing them in distilled water at 5 °C. The compressive modulus of the hydrogel increased with increasing heating time. X-ray diffraction studies reveal that the crystal structure of the internal layers of the TOCNs remained intact after the hydrothermal treatment and depigmentation. The hydrothermal treatment caused the hydrolysis of molecules, especially the glucuronate units, from the external layer of TOCN. The elimination of the glucuronate units decreased the net negative surface charge of the TOCNs, resulting in their aggregation into a three-dimensional network structure owing to the predominance of attractive forces. Such additive-free hydrogels that can be shaped into diverse forms are promising for medical applications.

Essentials We generated recombinant rhodocytin that could aggregate platelets via CLEC-2. Recombinant wild-type rhodocytin formed heterooctamer with four α- and β-subunits. Asp 4 in α-subunit of rhodocytin was required for binding to CLEC-2. Inhibitory mutant of rhodocytin blocked podoplanin-dependent hematogenous metastasis., Summary: Background Rhodocytin, a disulfide-linked heterodimeric C-type lectin from Calloselasma rhodostoma consisting of α-subunits and β-subunits, induces platelet aggregation through C-type lectin-like receptor 2 (CLEC-2). CLEC-2 is a physiological binding partner of podoplanin (PDPN), which is expressed on some tumor cell types, and is involved in tumor cell-induced platelet aggregation and tumor metastasis. Thus, modified rhodocytin may be a possible source of anti-CLEC-2 drugs for both antiplatelet and antimetastasis therapy. However, its molecular function has not been well characterized, because of the lack of recombinant rhodocytin that induces platelet aggregation. Objective To produce recombinant rhodocytin, in order to verify its function with mutagenesis, and to develop an anti-CLEC-2 drug based on the findings. Methods We used Chinese hamster ovary cells to express recombinant rhodocytin (wild-type [WT] and mutant), which was analyzed for induction/inhibition of platelet aggregation with light transmission aggregometry, the formation of multimers with blue native PAGE, and binding to CLEC-2 with flow cytometry. Finally, we investigated whether mutant rhodocytin could suppress PDPN-induced metastasis in an experimental lung metastasis mouse model. Results Functional WT] rhodocytin (αWTβWT) was obtained by coexpression of both subunits. Asp4 in α-subunits of rhodocytin was required for CLEC-2 binding. αWTβWT formed a heterooctamer similarly to native rhodocytin. Moreover, an inhibitory mutant of rhodocytin (αWTβK53A/R56A), forming a heterotetramer, bound to CLEC-2 without inducing platelet aggregation, and blocked CLEC-2-PDPN interaction-dependent platelet aggregation and experimental lung metastasis. Conclusion These findings provide molecular characterization information on rhodocytin, and suggest that mutant rhodocytin could be used as a therapeutic agent to target CLEC-2., (© 2018 International Society on Thrombosis and Haemostasis.)

Immune responses to parasitic pathogens are affected by the host physiological condition. High-density lipoprotein (HDL) and low-density lipoprotein (LDL) are transporters of lipids between the liver and peripheral tissues, and modulate pro-inflammatory immune responses. Pathogenic mycobacteria are parasitic intracellular bacteria that can survive within macrophages for a long period. Macrophage function is thus key for host defense against mycobacteria. These basic facts suggest possible effects of HDL and LDL on mycobacterial diseases, which have not been elucidated so far. In this study, we found that HDL and not LDL enhanced mycobacterial infections in human macrophages. Nevertheless, we observed that HDL remarkably suppressed production of tumor necrosis factor alpha (TNF-α) upon mycobacterial infections. TNF-α is a critical host-protective cytokine against mycobacterial diseases. We proved that toll-like receptor (TLR)-2 is responsible for TNF-α production by human macrophages infected with mycobacteria. Subsequent analysis showed that HDL downregulates TLR2 expression and suppresses its intracellular signaling pathways. This report demonstrates for the first time the substantial action of HDL in mycobacterial infections to human macrophages.

Barium titanate (BaTiO3, hereafter BT) is an established ferroelectric material first discovered in the 1940s and still widely used because of its well-balanced ferroelectricity, piezoelectricity, and dielectric constant. In addition, BT does not contain any toxic elements. Therefore, it is considered to be an eco-friendly material, which has attracted considerable interest as a replacement for lead zirconate titanate (PZT). However, bulk BT loses its ferroelectricity at approximately 130 °C, thus, it cannot be used at high temperatures. Because of the growing demand for high-temperature ferroelectric materials, it is important to enhance the thermal stability of ferroelectricity in BT. In previous studies, strain originating from the lattice mismatch at hetero-interfaces has been used. However, the sample preparation in this approach requires complicated and expensive physical processes, which are undesirable for practical applications. In this study, we propose a chemical synthesis of a porous material as an alternative means of introducing strain. We synthesized a porous BT thin film using a surfactant-assisted sol-gel method, in which self-assembled amphipathic surfactant micelles were used as an organic template. Through a series of studies, we clarified that the introduction of pores had a similar effect on distorting the BT crystal lattice, to that of a hetero-interface, leading to the enhancement and stabilization of ferroelectricity. Owing to its simplicity and cost effectiveness, this fabrication process has considerable advantages over conventional methods.

C-type lectin-like receptor 2 (CLEC-2) has been identified on the surface of platelets as a receptor for a platelet activating snake venom, rhodocytin/aggretin. CLEC-2 belongs to a C-type lectin superfamily and binds to a sialoglycoprotein, podoplanin, in vivo. Platelets play a crucial role in hemostasis and thrombosis, but recent studies have uncovered multiple roles of platelets beyond hemostasis in physiology and pathology. The interaction between platelet CLEC-2 and podoplanin is the key to several roles of platelets beyond hemostasis. The spatial and temporal expression patterns of podoplanin regulate vascular/lymphatic development, maintenance of vascular integrity, tissue regeneration, and some pathological processes including tumor metastasis and thromboinflammation. CLEC-2 facilitates blood/lymphatic vessel separation during embryonic development by binding to podoplanin on lymphatic endothelial cells. The leakage of platelets from hyperpermeable vessels for maintaining vascular integrity during inflammation depends on CLEC-2. During wound healing, the expression of podoplanin in keratinocytes is upregulated, which helps in the process. Podoplanin is expressed on the surface of tumor cells and facilitates hematogenous metastasis by inducing platelet aggregation through CLEC-2. During thrombotic processes, such as development of deep vein thrombosis, podoplanin is upregulated on unknown cells in the vessel wall in the area of inflammation, facilitates thrombus formation, and promotes further inflammation by binding to CLEC-2. In this article, the roles of platelets beyond hemostasis are comprehensively reviewed., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

We present an overview of recent investigations on the dielectric/ferroelectric properties of Dion-Jacobson-type perovskites, including bulk 3D layered systems and their exfoliated 2D nanosheets. In contrast to the Ruddlesden-Popper and Aurivillius phases, the Dion-Jacobson phases in bulk 3D systems have not been important targets for constructing dielectric/ferroelectric materials. However, recent investigations on Dion-Jacobson phases have provided new impetus to dielectric/ferroelectric materials. Dion-Jacobson perovskites can also facilitate delamination into 2D nanosheets. Layer-by-layer engineering of 2D perovskite nanosheets has a great potential for the rational design of new high-k dielectric/ferroelectric materials and nanodevices.

Long poly-diacetylene chains are excellent candidates for planar, on-surface synthesized molecular electronic wires. Since hexagonal-Boron Nitride (h-BN) was identified as the best available atomically flat insulator for the deposition of poly-diacetylene precursors, we demonstrate the polymerization patterns and rate on it under UV-light irradiation, with subsequent polymer identification by atomic force microscopy. The results on h-BN indicate self-sensitization which yields blocks comprised of several polymers, unlike on the well-studied graphite/diacetylene system, where the polymers are always isolated. In addition, the photo-polymerization proceeds at least 170 times faster on h-BN, where it also results in longer polymers. Both effects are explained by the h-BN bandgap, which is larger than the diacetylene electronic excitation energy, thus allowing the transfer of excess energy absorbed by polymerized wires to adjacent monomers, triggering their polymerization. This work sets the stage for conductance measurements of single molecular poly-diacetylene wires on h-BN.

S-allyl-glutathione (SAG) is one of the metabolites of diallyl sulfide (DAS), a component of garlic. DAS has shown preventative effects on carcinogenesis in animal models. However, whether synthetic SAG can improve liver fibrosis has not been investigated. We examined the potential preventive effects of SAG on acute and chronic models of liver fibrosis by chronic carbon tetrachloride (CCl 4 ) administration. SAG inhibited liver fibrogenesis induced by CCl 4 in a dose-dependent manner and reduced heat shock protein-47 (HSP47), a collagen-specific chaperone, and other fibrosis markers. In fibrosis regression models, after administration of either CCl 4 for 9 wk or dimethyl nitrosamine (DMN) for 6 wk, SAG markedly accelerated fibrolysis in both models. In the regression stage of DMN-treated liver, SAG normalized the ratio of M2 phenotype (expression of mannose receptor) in Kupffer cells (KCs). Consistent with these results, the culture supernatants of SAG-treated M2-phenotype KCs inhibited collagen- α1 (I) chain (COL1A1) mRNA expression in primary culture-activated rat hepatic stellate cells (HSCs). However, SAG did not directly inhibit HSC activation. In an acute model of CCl 4 single injection, SAG inhibited hepatic injury dose dependently consistent with the inhibited the elevation of the bilirubin and ALT levels. These findings suggest that SAG could improve the fibrogenic and fibrolysis cascade via the regulation of excess activated and polarized KCs. SAG may also serve as a preventive and therapeutic agent in fibrosis of other organs for which current clinical therapy is unavailable. NEW & NOTEWORTHY S-allyl-glutathione (SAG) is a metabolite of diallyl sulfide, a component of garlic. SAG increased hepatic glutathione levels and GSH-to-GSSG ratio in normal rats. SAG treatment before or after liver fibrosis from chronic CCl 4 administration improved liver fibrosis and regression. SAG decreased heat shock protein-47 (HSP47), a collagen-specific chaperone, and other fibrosis markers in CCl 4 -treated livers. SAG-treated Kupffer cell conditioned medium also inhibited collagen- α1 (I) chain (COL1A1) mRNA expression and other markers in primary culture hepatic stellate cells.

The aim of the study is to clarify the role of hypoxia-inducible factor-1 (HIF-1) in the development of renal fibrosis in mouse obstructive nephropathy. We used mice with floxed HIF-1α alleles and tamoxifen-inducible Cre/ERT2 recombinase under ubiquitin C promoter to induce global HIF-1α deletion. Following tamoxifen administration, mice were subjected to unilateral ureteral obstruction (UUO). At 3, 7 and 14 days after UUO, renal gene expression profiles and interstitial fibrosis were assessed. HIF-1 dependent up-regulation of prolyl hydroxylase 3 and glucose transporter-1 was observed in the obstructed kidney at 3 and 7 days but not at 14 days after UUO. Various factors promoting fibrosis were up-regulated during the development of fibrosis. HIF-1 dependent gene expression of profibrotic molecules, plasminogen activator inhibitor 1, connective tissue growth factor, lysyl oxidase like 2 and transglutaminase 2 was observed in the obstructed kidney but such HIF-1 dependency was limited to the early onset of renal fibrosis. Global HIF-1 deletion tended to attenuate interstitial collagen I deposition at 3 days but had no effects thereafter. It is suggested that HIF-1 dependent profibrogenic mechanisms are operating at the early onset of renal fibrosis but its contribution declines with the progression in mouse UUO model., (Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease with increased immunoglobulin E (IgE) levels. Activation of the mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (p70S6K) signaling is known to occur in the inflammatory regions of AD skin. We previously demonstrated that red ginseng extract (RGE), as an anti-inflammatory agent, had potential for treating AD. However, it is still unclear whether RGE inhibits mTOR/p70S6K signaling. Thus, we examined the anti-inflammatory effects of RGE on IgE or interferon-γ (IFN-γ) induced signaling pathways. In KU812 human basophils, activation of Fcε receptor type Iα (FCεRI), also known as the high affinity IgE receptor, induced phosphorylation of both mTOR and p70S6K. Moreover, levels of phosphorylated p70S6K (p-p70S6K), but not p-mTOR, were decreased by RGE. RGE also decreased p-p70S6K levels in IFN-γ-stimulated human keratinocytes, suppressing the IFN-γ induced increase in levels of C-C chemokine ligand 2 mRNA. Interestingly, the increased p70S6K phosphorylation in skin lesions of AD model mice was attenuated by RGE treatment. In conclusion, RGE is a potential therapy against inflammatory responses involving the p70S6K signaling pathway., (Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

An unambiguous structural characterization of the water-soluble Aureobasidium pullulans β-(1→3, 1→6)-glucan is yet to be achieved, although this β-(1→3, 1→6)-glucan is expected to exhibit excellent biofunctional properties. Thus, we herein report the elucidation of the primary structure of the A. pullulans β-(1→3, 1→6)-glucan using nuclear magnetic resonance spectroscopy, followed by comparison of the obtained structure with that of schizophyllan (SPG). Structural characterization of the A. pullulans β-(1→3, 1→6)-glucan revealed that the structural units are a β-(1→3)-d-glucan backbone with four β-(1→6)-d-glucosyl side branching units every six residues. In addition, circular dichroism spectroscopic analysis revealed that the β-(1→3, 1→6)-glucan interacted with polyadenylic acid (poly(A)) chains in DMSO solution to form a complex similar to that obtained in the complexation of SPG/poly(A). This finding indicates that β-(1→3, 1→6)-glucan forms a triple-helical conformation in aqueous solution but exhibits a random coil structure in DMSO solution, which is similar to the behavior of SPG., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

This article contains two-dimensional (2D) NMR experimental data, obtained by the Bruker BioSpin 500 MHz NMR spectrometer (Germany) which can used for the determination of primary structures of schizophyllan from Schizophyllum commune (SPG) and a water-soluble β-(1→3, 1→6)-glucan from Aureobasidium pullulans . Data include analyzed the 2D NMR spectra of these β-glucans, which are related to the subject of an article in Carbohydrate Polymers , entitled "NMR spectroscopic structural characterization of a water-soluble β-(1→3, 1→6)-glucan from A. pullulans " (Kono et al., 2017) [1]. Data can help to assign the 1 H and 13 C chemical shifts of the structurally complex polysaccharides.

Background: Large-scale schistosomiasis control programs are implemented in regions with diverse social and economic environments. A key epidemiological feature of schistosomiasis is its small-scale heterogeneity. Locally profiling disease dynamics including risk factors associated with its transmission is essential for designing appropriate control programs. To determine spatial distribution of schistosomiasis and its drivers, we examined schoolchildren in Kwale, Kenya., Methodology/principal Findings: We conducted a cross-sectional study of 368 schoolchildren from six primary schools. Soil-transmitted helminths and Schistosoma mansoni eggs in stool were evaluated by the Kato-Katz method. We measured the intensity of Schistosoma haematobium infection by urine filtration. The geometrical mean intensity of S. haematobium was 3.1 eggs/10 ml urine (school range, 1.4-9.2). The hookworm geometric mean intensity was 3.2 eggs/g feces (school range, 0-17.4). Heterogeneity in the intensity of S. haematobium and hookworm infections was evident in the study area. To identify factors associated with the intensity of helminth infections, we utilized negative binomial generalized linear mixed models. The intensity of S. haematobium infection was associated with religion and socioeconomic status (SES), while that of hookworm infection was related to SES, sex, distance to river and history of anthelmintic treatment., Conclusions/significance: Both S. haematobium and hookworm infections showed micro-geographical heterogeneities in this Kwale community. To confirm and explain our observation of high S. haematobium risk among Muslims, further extensive investigations are necessary. The observed small scale clustering of the S. haematobium and hookworm infections might imply less uniform strategies even at finer scale for efficient utilization of limited resources.

We have investigated whether acidity can be used to control the physicochemical properties of chitin nanofibers (ChNFs). In this study, we define acidity as the molar ratio of dissociated protons from the acid to the amino groups in the raw chitin powder. The effect of acidity on the physicochemical properties of α- and β-ChNFs was compared. The transmittance and viscosity of the β-ChNFs drastically and continuously increased with increasing acidity, while those of the α-ChNFs were not affected by acidity. These differences are because of the higher ability for cationization based on the more flexible crystal structure of β-chitin than α-chitin. In addition, the effect of the acid species on the transmittance of β-ChNFs was investigated. The transmittance of β-ChNFs can be expressed by the acidity regardless of the acid species, such as hydrochloric acid, phosphoric acid, and acetic acid. These results indicate that the acidity defined in this work is an effective parameter to define and control the physicochemical properties of ChNFs., (Copyright © 2017 Elsevier B.V. All rights reserved.)