Neurotropin suppresses inflammatory cytokine expression and cell death through suppression of NF-κB and JNK in hepatocytes.

Inflammatory response and cell death in hepatocytes are hallmarks of chronic liver disease, and, therefore, can be effective therapeutic targets. Neurotropin® (NTP) is a drug widely used in Japan and China to treat chronic pain. Although NTP has been demonstrated to suppress chronic pain through the descending pain inhibitory system, the action mechanism of NTP remains elusive. We hypothesize that NTP functions to suppress inflammatory pathways, thereby attenuating disease progression. In the present study, we investigated whether NTP suppresses inflammatory signaling and cell death pathways induced by interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα) in hepatocytes. NTP suppressed nuclear factor-κB (NF-κB) activation induced by IL-1β and TNFα assessed by using hepatocytes isolated from NF-κB-green fluorescent protein (GFP) reporter mice and an NF-κB-luciferase reporter system. The expression of NF-κB target genes, Il6, Nos2, Cxcl1, ccl5 and Cxcl2 induced by IL-1β and TNFα was suppressed after NTP treatment. We also found that NTP suppressed the JNK phosphorylation induced by IL-1β and TNFα. Because JNK activation contributes to hepatocyte death, we determined that NTP treatment suppressed hepatocyte death induced by IL-1β and TNFα in combination with actinomycin D. Taken together, our data demonstrate that NTP attenuates IL-1β and TNFα-mediated inflammatory cytokine expression and cell death in hepatocytes through the suppression of NF-κB and JNK. The results from the present study suggest that NTP may become a preventive or therapeutic strategy for alcoholic and non-alcoholic fatty liver disease in which NF-κB and JNK are thought to take part

The Cell Shape-determining Csd6 Protein from Helicobacter pylori Constitutes a New Family of L,D-Carboxypeptidase

Helicobacter pylori causes gastrointestinal diseases, including gastric cancer. Its high motility in the viscous gastric mucosa facilitates colonization of the human stomach and depends on the helical cell shape and the flagella. In H. pylori, Csd6 is one of the cell shape-determining proteins that play key roles in alteration of cross-linking or by trimming of peptidoglycan muropeptides. Csd6 is also involved in deglycosylation of the flagellar protein FlaA. To better understand its function, biochemical, biophysical, and structural characterizations were carried out. We show that Csd6 has a three-domain architecture and exists as a dimer in solution. The N-terminal domain plays a key role in dimerization. The middle catalytic domain resembles those of L,D-transpeptidases, but its pocket-shaped active site is uniquely defined by the four loops I to IV, among which loops I and III show the most distinct variations from the known L,D-transpeptidases. Mass analyses confirm that Csd6 functions only as an L,D-carboxypeptidase and not as an L,D-transpeptidase. The D-Ala-complexed structure suggests possible binding modes of both the substrate and product to the catalytic domain. The C-terminal nuclear transport factor 2-like domain possesses a deep pocket for possible binding of pseudaminic acid, and in silico docking supports its role in deglycosylation of flagellin. On the basis of these findings, it is proposed that H. pylori Csd6 and its homologs constitute a new family of L,D-carboxypeptidase. This work provides insights into the function of Csd6 in regulating the helical cell shape and motility of H. pylori.1165Ysciescopu

A study on the sharp knee and fine structures of cosmic ray spectra

The paper investigates the overall and detailed features of cosmic ray (CR) spectra in the knee region using the scenario of nuclei-photon interactions around the acceleration sources. Young supernova remnants can be the physical realities of such kind of CR acceleration sites. The results show that the model can well explain the following problems simultaneously with one set of source parameters: the knee of CR spectra and the sharpness of the knee, the detailed irregular structures of CR spectra, the so-called "component B" of Galactic CRs, and the electron/positron excesses reported by recent observations. The coherent explanation serves as evidence that at least a portion of CRs might be accelerated at the sources similar to young supernova remnants, and one set of source parameters indicates that this portion mainly comes from standard sources or from a single source.Comment: 13 pages, 4 figures, accepted for publication in SCIENCE CHINA Physics, Mechanics & Astronomy

A self-rectifying TaOy/nanoporous TaOx memristor synaptic array for learning and energy-efficient neuromorphic systems

The human brain intrinsically operates with a large number of synapses, more than 10(15). Therefore, one of the most critical requirements for constructing artificial neural networks (ANNs) is to achieve extremely dense synaptic array devices, for which the crossbar architecture containing an artificial synaptic node at each cross is indispensable. However, crossbar arrays suffer from the undesired leakage of signals through neighboring cells, which is a major challenge for implementing ANNs. In this work, we show that this challenge can be overcome by using Pt/TaOy/nanoporous (NP) TaOx/Ta memristor synapses because of their self-rectifying behavior, which is capable of suppressing unwanted leakage pathways. Moreover, our synaptic device exhibits high non-linearity (up to 10(4)), low synapse coupling (S.C, up to 4.00 x 10(-5)), acceptable endurance (5000 cycles at 85 degrees C), sweeping (1000 sweeps), retention stability and acceptable cell uniformity. We also demonstrated essential synaptic functions, such as long-term potentiation (LTP), long-term depression (LTD), and spiking-timing-dependent plasticity (STDP), and simulated the recognition accuracy depending on the S.C for MNIST handwritten digit images. Based on the average S.C (1.60 x 10(-4)) in the fabricated crossbar array, we confirmed that our memristive synapse was able to achieve an 89.08% recognition accuracy after only 15 training epochs

ICEberg: a web-based resource for integrative and conjugative elements found in Bacteria

ICEberg (http://db-mml.sjtu.edu.cn/ICEberg/) is an integrated database that provides comprehensive information about integrative and conjugative elements (ICEs) found in bacteria. ICEs are conjugative self-transmissible elements that can integrate into and excise from a host chromosome. An ICE contains three typical modules, integration and excision, conjugation, and regulation modules, that collectively promote vertical inheritance and periodic lateral gene flow. Many ICEs carry likely virulence determinants, antibiotic-resistant factors and/or genes coding for other beneficial traits. ICEberg offers a unique, highly organized, readily explorable archive of both predicted and experimentally supported ICE-relevant data. It currently contains details of 428 ICEs found in representatives of 124 bacterial species, and a collection of >400 directly related references. A broad range of similarity search, sequence alignment, genome context browser, phylogenetic and other functional analysis tools are readily accessible via ICEberg. We propose that ICEberg will facilitate efficient, multi-disciplinary and innovative exploration of bacterial ICEs and be of particular interest to researchers in the broad fields of prokaryotic evolution, pathogenesis, biotechnology and metabolism. The ICEberg database will be maintained, updated and improved regularly to ensure its ongoing maximum utility to the research community

Enhancement of monoclonal antibody productivity by promoting active hypothermic growth in hybridoma cells

BACKGROUND: Many reports have suggested that mild hypothermic culture conditions improve the specific monoclonal antibody (mAb) productivity of mammalian cells. The effect of active hypothermic growth on the mAb productivity of the hybridoma C2E7 was investigated. Hybridoma growth under hypothermic conditions (32 °C) was stimulated by supplementation of the culture medium with high serum concentrations (up to 30%). RESULTS: Specific and volumetric mAb productivity of a stimulated, active growth, mildly hypothermic hybridoma culture (30% FBS supplemented, 32 °C) were 1.38‐ and 1.34‐fold greater than the control culture (10% FBS supplemented, 37 °C). The enhanced specific mAb productivity under hypothermic conditions was associated with an increase in IgM mRNA levels during both the lag and early exponential phases of hypothermic growth. CONCLUSION: Stimulation of hybridoma growth under mildly hypothermic conditions increased both the specific and volumetric mAb productivity of hybridoma cells

Vibrational spectroscopy and microwave dielectric properties of AY2Si3O10 (A=Sr, Ba) ceramics for 5G applications

AY2Si3O10 (A = Sr, Ba) trisilicate ceramics were synthesized by traditional high temperature solid state reaction method. X-ray diffraction patterns and Rietveld refinement revealed that AY2Si3O10 (A = Sr, Ba) ceramics belonged to triclinic and monoclinic crystal systems with Pī and P21/m space groups, respectively. The vibrational modes of [SiO4] tetrahedra, [YO6] octahedra and [(Sr/Ba)O8] polyhedra were analyzed by Raman spectroscopy. The infrared spectroscopy fitting analysis was used to determine intrinsic dielectric properties. Excellent microwave dielectric properties were measured for SrY2Si3O10 and BaY2Si3O10 with ɛr = 9.3, Qf = 64100 GHz, τf = −31 ppm/°C and ɛr = 9.5, Qf = 65600 GHz, τf = −28 ppm/°C, respectively. Both trisilicate ceramics are considered potential candidates for 5G and mm wave technology, provided τf can be further tuned

Highly efficient perovskite solar cells with crosslinked PCBM interlayers

This research has received (partial) funding from the Flemish Government – Department of Economics, Science and Innovation. This work has been partially supported by Solliance, a partnership of R&D organizations from Belgium, the Netherlands, and Germany working in thin film photovoltaic solar energy