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Abstract [Introduction] Seven smoke constituents, including hydrogen cyanide (HCN), ammonia (NH 3), phenol, benzo[α]pyrene (B[a]P), carbon monoxide (CO)¸ crotonaldehyde, and 4-(methylnitrosamino)-1- (3-pyridyl)-1-butanone (NNK), are proposed be the most relevant constituents for smoking-related diseases. [Methods] Different combinations of leaf stalk positions, varieties and locations were used to create variable chemistry of cigarette filler and smoke. Experimental cigarettes were measured for emission level of seven smoke toxicants and content of seventy-three filler components. [Results] The ranges of coefficient of variation (CV) for seven smoke toxicants were 15.43%–43.15%. The emission pattern of NNK and crotonaldehyde were different from that of other five smoke toxicants. Most of the seven smoke toxicants were influenced in following order: stalk position > location > variety. The leaf constitutes closely correlated with seven smoke toxicants were analyzed. [Conclusions] The results showed that seven toxicants were significantly influenced by leaf position and location, and closely correlated with leaf components, such as potassium, malate and alkaloid contents. The results provide useful and comprehensive information on the affecting factors and correlating leaf constituents for the variations of seven smoke toxicants. Graphical abstract Image 1 Highlights • HCN, NH 3 , phenol, B[a]P, CO¸ crotonaldehyde, and NNK, are relevant constituents for smoking-related diseases. • Tobacco from different leaf stalk positions, varieties and locations were used for cigarette fillers. • Experimental cigarettes were measured for emission level of seven toxicants and content of seventy-three filler components. • Seven toxicants were influenced by stalk position and location, and correlated with potassium, malate and alkaloid in leaf. [ABSTRACT FROM AUTHOR]

The ultrasonic guided wave has emerged as a promising tool for structural health monitoring (SHM) and nondestructive testing (NDT) due to their capability to propagate over long distances with minimal loss and sensitivity to both surface and subsurface defects. The dispersion effect degrades the temporal and spatial resolution of guided waves. A novel ultrasonic guided wave processing method for both single mode and multi-mode guided waves dispersion compensation is proposed in this work based on compressed sensing, in which a dispersion signal dictionary is built by utilizing the dispersion curves of the guided wave modes in order to sparsely decompose the recorded dispersive guided waves. Dispersion-compensated guided waves are obtained by utilizing a non-dispersion signal dictionary and the results of sparse decomposition. Numerical simulations and experiments are implemented to verify the effectiveness of the developed method for both single mode and multi-mode guided waves. [ABSTRACT FROM AUTHOR]

Immature dendritic cells (iDCs) have been shown to be able to induce peripheral T-cell tolerance through distinct pathways. Here, we investigated the tolerogenic property of recipient iDCs whose maturation was arrested by a dominant negative mutant of inhibitor of nuclear factor kappa-B kinase 2 (dnIKK2) gene. We found that dnIKK2-iDCs presented a typical semi-mature morphology and expressed lower levels of CD80 and CD86, slightly higher MHC-II than untransfected iDCs. The expression of these molecules had no significant change even dnIKK2-iDCs were pulsed by donor antigen. In primary mixed leukocyte reaction (MLR), dnIKK2-iDCs exhibited impaired ability to stimulate allogeneic T-cells, but induced CD4 + CD25 − T-cell formation. In co-culture MLR, these CD4 + CD25 − T-cells suppressed T-cell alloreaction in an antigen-specific manner. Besides, CD4 + CD25 − T-cells inhibited IL-2 and IFN-γ release, whereas promoted IL-10 and TGF-β secretion. These data suggested recipient dnIKK2-iDCs could maintain peripheral tolerance through down-regulating costimulatory molecule expressions and inducing CD4 + CD25 − T-cell formation. [ABSTRACT FROM AUTHOR]

Abstract: The glycocalyx on the surface of endothelium lining blood vessel walls modulates vascular barrier function, cell adhesion and also serves as a mechano-sensor for blood flow. Reduction of glycocalyx has been reported in many diseases including atherosclerosis, inflammation, myocardial edema, and diabetes. The surface glycocalyx layer (SGL) is composed of proteoglycans and glycosaminoglycans, of which heparan sulfate is one of the most abundant. To quantify the SGL thickness on the microvessels of rat mesentery and mouse cremaster muscle in situ, we applied a single vessel cannulation and perfusion technique to directly inject FITC-anti-heparan sulfate into a group of microvessels for immuno-labeling the SGL. We also used anti-heparan sulfate for immuno-labeling the SGL on rat and mouse aortas ex vivo. High resolution confocal microscopy revealed that the thickness of the SGL on rat mesenteric capillaries and post-capillary venules is 0.9±0.1μm and 1.2±0.3μm, respectively; while the thickness of the SGL on mouse cremaster muscle capillaries and post-capillary venules is 1.5±0.1μm and 1.5±0.2μm, respectively. Surprisingly, there was no detectable SGL in either rat mesenteric or mouse cremaster muscle arterioles. The SGL thickness is 2.5±0.1μm and 2.1±0.2μm respectively, on rat and mouse aorta. In addition, we observed that the SGL is continuously and evenly distributed on the aorta wall but not on the microvessel wall. [Copyright &y& Elsevier]

Abstract: Neuroglobin (Ngb), a newly identified globin in vertebrate brain, has been suggested to be able to protect against brain hypoxic–ischemic injury. However, owing to its large size, the impermeability of the blood–brain barrier (BBB) to Ngb limits its application in brain injury. Recently, the 11-amino-acid human immunodeficiency virus trans-activator of transcription (TAT) protein transduction domain was shown to successfully deliver macromolecules into the brain. This study explored whether the TAT–Ngb fusion protein can cross the BBB and protect the brain from cerebral ischemia. The TAT–Ngb fusion protein generated from Escherichia coli BL21 (DE3) was efficiently delivered into mice brain tissues by intravenous injection as demonstrated by immunohistochemistry and Western blotting. Two groups of mice were treated with filamentous middle cerebral artery occlusion (MCAO) for 30min or 2h followed by reperfusion. Each group was then divided into sub-groups and was injected intravenously with TAT–Ngb, Ngb, or saline respectively before MCAO or immediately after reperfusion. Compared with the Ngb- and saline-treated group, the group with TAT–Ngb treated 2h before MCAO showed significantly less brain infarct volume and had better neurologic outcomes (p <0.05). Furthermore, a TAT–Ngb injection following a 30-min MCAO treatment significantly increased neuronal survival in the striatum (p <0.05). Our results demonstrated that the exogenous Ngb fusion protein containing the TAT protein transduction domain could be efficiently transduced into neurons in the mouse and protect the brain from mild or moderate ischemic injury. [ABSTRACT FROM AUTHOR]

Phytoremediation is an essential technique for mines' ecological restoration. Modifiers addition can alleviate the stress of heavy metals to plants and enhanced remediation efficiency. Herein, spent mushroom compost (SMC) and calcium carbonate (CaCO 3) were added to lead-zinc mine tailings to reveal the mechanism of Macleaya cordata adaptive to heavy metals stress. Pot experiments were conducted in 100% tailing (T), 90% tailing + 5% SMC + 5% CaCO 3 (T+), and 100% natural soil (NS). The results indicate that SMC and CaCO 3 amendments could improve the structure and fertility of tailings, and promote the growth of M. cordata , increase the content of heavy metals accumulated in plants, enhance the synthesis of chlorophyll and increas the content of soluble protein in leaves; enhance the activities of antioxidase, that can protectcelluar components from oxidative damage. Moreover, most of Pb, Zn, and Cd existed in the cell wall and soluble components, adding SMC and CaCO 3 could promote the conversion of Pb, Zn, and Cd to chemical forms with less toxicity and migratory capability. The results of transmission electron microscopy (TEM) and Fourier transform infrared spectrometer (FTIR) showed that SMC and CaCO 3 could protect the structural integrity of cells and increase the contents of –OH, –COOH functional groups that can bind to heavy metals in cells. The addition of SMC and CaCO 3 can alleviate the stress of heavy metals on M. cordata , enhancing its adaptability to heavy metals and phytoremediation capacity. • The SMC and CaCO 3 amendments could strengthen the phytoremediation potential. • Fixation of cell wall play an important role in reducing the stress of Pb, Zn and Cd. • Antioxidant enzyme system effectively reduce the stress of Pb, Zn and Cd to plant. • The SMC and CaCO 3 amendments could alleviate the damage of cell structure. [ABSTRACT FROM AUTHOR]

Abstract: Populus is a model system for investigating the wood development, crown formation, and disease resistance in perennial plants. AR2/ERF is a large family of transcription factors in plant, encoding transcriptional regulators with a variety of functions involved in the developmental and physiological processes. Here, starting from database of Populus genome, we identified 200 AP2/ERF genes by in silico cloning method using the AP2/ERF conserved domain amino acid sequence of Arabidopsis thaliana as probe. Based on the number of AP2/ERF domains and the function of the genes, those AP2/ERF genes from Populus were classified into four subfamilies named the AP2, DREB, ERF, RAV, and a soloist. Among these genes, the number genes of total AP2/ERF family genes, DREB subfamily, and ERF subfamily from Populus trichocarpa were about 1.4–1.6-fold than those from A. thaliana. The rates were very similar for the putative homologs between Populus and Arabidopsis. [Copyright &y& Elsevier]

Abstract: The alternatively spliced type III extradomain B (EIIIB) of fibronectin (FN) is expressed only during embryogenesis, wound healing and tumorigenesis. The biological function of this domain is unclear. We describe here the first crystal structure of the interface between alternatively spliced EIIIB and its adjacent FN type III domain 8 (FN B-8). The opened CC′ loop of EIIIB, and the rotation and tilt of EIIIB allow good access to the FG loop of FN-8, which is normally hindered by the CC′ loop of FN-7. In addition, the AGEGIP sequence of the CC′′ loop of EIIIB replaces the NGQQGN sequence of the CC′ loop of FN-7. Finally, the CC′′ loop of EIIIB forms an acidic groove with FN-8. These structural findings warrant future studies directed at identifying potential binding partners for FN B-8 interface, linking EIIIB to skeletal and cartilaginous development, wound healing, and tumorigenesis, respectively. [Copyright &y& Elsevier]

[Display omitted] In the biological environment, mineral crystals exquisitely controlled by biomacromolecules often show intricate hierarchical structures and superior mechanical properties. Among these biominerals, spicules, hybrid silica/protein superstructures serving as skeletal elements in demosponges, represent an excellent example for motivating the synthesis of silica materials. Herein, by designing sequence-defined peptoids containing side chains with a strong binding to silica, we demonstrated that self-assembly of these peptoids into fiber structures enables the mimicking of both biocatalytic and templating functions of silicatein filaments for the formation of silica fibers at near-neutral pH and ambient temperature. We further showed that the presence of amino groups is significant for the nucleation of silica on self-assembled peptoid nanofibers. Molecular dynamics simulation further confirmed that having silica-binding of amino side chains is critical for self-assembled peptoid fibers in triggering silica formation. We demonstrated that tuning inter-peptoid interactions by varying carboxyl and amino side chains significantly influences the assembly kinetics and final morphologies of peptoid assemblies as scaffolds for directing silica mineralization to form silica spheres, fibers, and sheets. The formation of silica shell on peptoid fibers increased the mechanical property of peptoid hydrogel materials by nearly 1000-fold, highlighting the great potential of using silicification to enhance the mechanical property of hydrogel materials for applications including tissue engineering. Since peptoids are highly robust and programmable, we expect that self-assembly of peptoids containing solid-binding side chains into hierarchical materials opens new opportunities in the design and synthesis of highly tunable scaffolds that direct the formation of composite nanomaterials. [ABSTRACT FROM AUTHOR]

Background Increasing evidence has suggested that miR-330-5p can function as a tumor suppressor in different types of cancers. However, the effects and underlying mechanisms of miR-330-5p in the development of cutaneous malignant melanoma (CMM) remain largely unknown. The aim of the present study was to investigate the role of miR-330-5p in CMM and to determine the molecular mechanisms underlying its action. Materials and methods The expression level of miR-330-5p was detected in 26 cases of primary CMM tissues and cell lines by real-time quantitative polymerase chain reaction. We also assessed whether overexpression of miR-330-5p influences in vitro cell proliferation, invasion, and migration. Western blotting analysis was used to detect the influence of miR-330-5p on the targets, and Pearson analysis was used to calculate the correlation between the expression of targets gene and miR-330-5p in CMM tissues. Results Our study showed that miR-330-5p was downregulated in CMM tissues ( P = 0.010) and cell lines ( P < 0.05), and patients with high mitotic activity showed lower miR-330-5p expression levels ( P = 0.002). Enforced expression of miR-330-5p inhibits malignant CMM cells proliferation and migration and led to downregulation of the TYR and PDIA3 protein. Moreover, the expression level of miR-330-5p in CMM tissues showed inverse relationship with the expression level of TYR and PDIA3 protein. Conclusions In conclusion, our findings suggested that miR-330-5p represents a potential tumor-suppressive miRNA and plays an important role in CMM progression by suppressing TYR and PDIA3 expression. [ABSTRACT FROM AUTHOR]

Abstract: Hepatic progenitor cells (HPCs) persist in adulthood and have the potential to play a major role in regenerating diseased liver. However, the signaling pathways that both directly and indirectly regulate HPCs’ self-renewal and differentiation remain elusive. Previously, we identified a bipotent, stem cell antigen-1 (Sca-1) positive HPC population from naïve adult liver tissue. In the present study, we aimed to investigate the involvement of various signaling pathways in Sca-1+ HPC proliferation. Epidermal growth factor (EGF) supplementation shows a significant increase in Sca-1+ HPC proliferation and colony formation while stimulating phosphorylation of ERK1/2 and activating the induction of Cyclin D1. There were no demonstrable effects of EGF on Akt. The MEK inhibitor, PD0325901, inhibits proliferation and ERK1/2 phosphorylation while also suppressing the expression of Cyclin D1. In addition, activation of either IL-6/STAT3 or Wnt/β-Catenin pathway did not independently support cell proliferation and colony formation of HPCs. The Wnt/β-Catenin pathway can cooperate with EGF to significantly promote HPC colony formation ratio and maintain long-term HPC in vitro. The data indicates that the MAPK/ERK pathway is both essential and critical for HPC proliferation, and the Wnt signaling pathway is not sufficient, while it works synergistically with the MAPK/ERK signaling pathway to promote HPC proliferation. [Copyright &y& Elsevier]

Abstract: Human metallothionein-3 (hMT3), first isolated and identified as a neuronal growth inhibitory factor (GIF), is a metalloprotein expressed predominantly in brain. However, untill now, the exact mechanism of the bioactivity of hMT3 is still unknown. In order to study the influence of acid–base catalysis on S-nitrosylation of hMT3, we constructed the E23K mutant of hMT3. During the course of bioassay, we found out unexpectedly that mutation at E23 of hMT3 eliminates the neuronal growth inhibitory activity completely. To the best of our knowledge, it is the first report that other residues, besides the TCPCP motif, in the β-domain can alter the bioactivity of hMT3. In order to figure out the causes for the loss of bioactivity of the E23K mutant, the biochemical properties were characterized by UV–vis spectroscopy, CD spectroscopy, pH titration, DTNB reaction, EDTA reaction, and SNOC reaction. All data demonstrated that stability of the metal–thiolate cluster and overall structure of the E23K mutant were not altered too much. However, the reaction of the E23K mutant with SNOC exhibited biphasic kinetics and the mutant protein released zinc ions much faster than hMT3 in the initial step, while hMT3 exhibited single kinetic process. The 2D [1H–15N] HSQC was also employed to characterize structural changes during the reaction of hMT3 with varying mounts of nitric oxide. It was shown that the resonance of Glu23 disappeared at a molar ratio of NO to protein of 4. Based on these results, we suggest that mutation at Glu23 may alter the NO metabolism and/or affect zinc homeostasis in brain, thus altering the neuronal growth inhibitory activity. [Copyright &y& Elsevier]

• An algorithm is designed to reduce the network blocking rate. • Markov Decision Process based state transfer is provided for online RMSA in real-time. • Offline Deep Q-Network based algorithm is provided to get a well-trained Q-network helping the RMSA state transfer. • The experience priority replay mechanism and Sumtree are introduced to speed up Deep Q-Network training. The continuous growth of the network communication demand puts higher requirements on the network infrastructures. The elastic optical network (EON) has great potential to support the continued demands for communication bandwidth. Efficient use of bandwidth resources of EON has been particularly important to alleviate network blocking, which depends on routing, modulation, and spectrum allocation processes (RMSA). However, the time-varying states of EON caused by the uncertainty of future demands make it a lot tougher to realize the online RMSA in real time. To solve the above problem, this paper proposes a kind of Deep Q Network (DQN) algorithm with prioritized experience replay mechanism to perform the RMSA process in real-time. The proposed algorithm includes two parts. One is the Markov Decision Process (MDP) based state transfer for online RMSA by a trained Q-network. The other is an offline DQN-based algorithm for getting a trained Q-network to help the decision-making of RMSA state transfer, where the experience priority replay mechanism and Sumtree are introduced to speed up DQN training. Simulation results show that compared with the traditional Deep Q Network algorithm, the proposed algorithm nearly doubles the Q-network training speed. And compared with the traditional sp + ff algorithm, the trained Q-network reduces the blocking rate by nearly 35 %. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the role for Foxq1 in proliferation activity regulation of dental pulp stem cells (DPSCs). Proliferation of DPSC was induced by calcium hydroxide, then expression alteration of Foxq1 was evaluated. Lentivirus was employed to manipulate Foxq1 level in DPSC, and proliferation activities were evaluated. To look into mechanism regulating Foxq1 level after calcium hydroxide stimulation, expressions of various microRNAs were evaluated, then bioinformatics study and dual-luciferase study were carried out to confirm targeting relationship between microRNA and Foxq1. The result of our study indicated that proliferation activities of DPSCs were enhanced after calcium hydroxide stimulation, during which expression of Foxq1 was also up-regulated. Cell viability and progression from G1 to S phase were both improved with overexpression of Foxq1, and microRNAs profiling study and dual-luciferase result suggested miR-320b contributed to the up-regulation of Foxq1 after calcium hydroxide stimulation. These results suggested that miR-320b mediated Foxq1 up-regulation promote proliferation of dental pulp stem cells. [ABSTRACT FROM AUTHOR]

In vitro predatory activity of 157 native isolates of Arthrobotrys oligospora from China on larvae of trichostrongylides ( Trichostrongylus colubriformis and Haemonchus contortus ) in feces of sheep were assessed. The results showed that 135 of tested isolates of A. oligospora reduced the development of trichostrongylide larvae in feces by 90–99.99%, 11 isolates by 80–89.46% and 11 isolates by 14.58–78.82%. To understand their capacity of passing through gastrointestinal tract of sheep, 50 native isolates of A. oligospora were selected and assessed in sheep. Among these isolates, 16 isolates significantly reduced the number of larvae developing in the feces (P < 0.05); their percentage reduction of L3 ranged from 42.87% to 99.51% and the isolates tested were harvested in 5 g sub-samples of from sheep in each treatment group, indicating that these isolates had the capacity of preying larvae of trichostrongylides after the passage through gastrointestinal tract of sheep. The remaining isolates of A. oligospora were not able to survive after passage through gastrointestinal tract of sheep. In the following, the 16 isolates that presented more or less viability after sheep gastrointestinal passage were selected and assessed in goats. The results showed that the 11 isolates out of them could be able to pass through the digestive tract of goats without loss of ability of preying larvae of trichostrongylides in feces and their efficacies ranged from 53.88% to 94.28%, and that the isolates tested were harvested in 5 g sub-samples of feces from goats in each treatment group. In the current study, these isolates which demonstrated outstanding properties in vitro and could survive in the passage through the alimentary tract of sheep and goat should be potential candidates as a possible feed additive. [ABSTRACT FROM AUTHOR]

Abstract: Osteogenesis associated with persistent inflammation or infection exists in a broad range of conditions including rheumatoid arthritis and traumatic bone fracture. The poor outcomes of these conditions will benefit from more effective treatments. Here we investigated the molecular mechanisms and tested NEMO-binding domain peptide as a new approach of circumventing TNF-α inhibition of osteoblast differentiation. Our results showed: TNF-α markedly decreased BMP-2-induced alkaline phosphatase activity in the multipotent myoblast C2C12 cells in a dose dependent manner; stepwise experiments demonstrated that BMP-2-induced Smad1 activity was abrogated by addition of exogenous TNF-α or overexpression of NF-κB, and it was significantly elevated by overexpression of IκBα, an inhibitor of NF-κB; Western blotting showed that TNF-α markedly decreased the amount of phospho-Smad1 in BMP-2-activated C2C12 cells, but it did not alter Smad1 mRNA abundance as measured by real-time PCR; addition of a functional cell-permeable NEMO-binding domain (NBD) peptide antagonized NF-κB activity and ameliorated TNF-α inhibition of osteoblast differentiation. Taken together, our study reveals for the first time that NF-κB activation inhibits osteoblast differentiation by attenuating Smad1 activity and application of NBD peptide ameliorates this inhibitory effect. This could lead to new therapeutic drugs that circumvent the inflammatory inhibition of osteogenesis for treatment of traumatic open fractures with infection, rheumatoid arthritis and other bone loss disorders. [Copyright &y& Elsevier]

Abstract: It has been reported that the 6CPCP9 motif near the N-terminus is pivotal to the inhibitory activity of human neuronal growth inhibitory factor (hGIF). In order to better understand the biological significance of this region on the structure, property and function of hGIF, we introduced a highly flexible residue, Gly, either in front of the 6CPCP9 motif (the IG6 mutant, TGCPCP) or in the middle of it (the IG8 mutant, TCPGCP) and investigated their structural and metal binding properties in detail. The results showed that the overall structure and the stability of the metal-thiolate clusters of the two mutants were comparable to that of hGIF. However, the bioassay results showed that the bioactivity of the IG6 mutant decreased significantly, while the bioactivity of the IG8 mutant was almost abolished. Molecular dynamics simulation results showed that the backbone of the IG6 mutant exhibited high similarity to that of hGIF, and the two prolines could still induce structural constraints on the 6CPCP9 tetrapeptide and form a similar conformation with that of hGIF, however, the conformation of the first five amino acid residues in the N-terminus was quite different. In hGIF, the five residues are twisted and form a restricted conformation, while in the IG6 mutant this peptide extends more naturally and smoothly, which is similar to that of MT2. As to the IG8 mutant, the Gly insertion broke the 6CPCP9 motif, thus probably abolishing the interactions with other molecules and eliminating its inhibitory activity. Based on these results, we suggested that although the structure adopted by the 6CPCP9 motif is the determinant factor of the inhibitory bioactivity of hGIF, other residues within the N-terminal fragment (residue 1–13) may also influence the peptide conformation and contribute to the protein’s bioactivity. [Copyright &y& Elsevier]

Abstract: The subtraction method is a quick and economical technique to scan differential gene expression. However, most subtraction methods are limited by the complexity and length of cDNA samples. To overcome this problem, we developed a novel method to identify the unique full-length cDNAs in two complicated tissue or cell types. This method, duplex-specific nuclease (DSN)-mediated transcriptome subtraction (DTS), is based on the normalization strategy of the crab duplex-specific nuclease and the subtraction method of suppression subtractive hybridization. DSN eliminates nearly all of the common sequences in the tester and driver cDNA samples after the first hybridization step, ensures accurate discrimination between the tester and the driver cDNA samples, and enriches the full-length differential cDNAs from the tester. Using the DTS method, we have successfully identified an 1812-bp additional GUS gene from the complicated Arabidopsis seedling cDNA library. We also employed DTS to detect the differences in mRNA expression of salt-treated Arabidopsis seedlings to illustrate further the efficiency of the subtraction method. [Copyright &y& Elsevier]

Abstract: It was reported that expression of the estrogen-regulated zinc transporter LIV-1 was particularly high in human cervical cancer cell line HeLa. This result prompted us to study the role that LIV-1 played in human cervical cancer. The results of real-time PCR showed that LIV-1 mRNA was significantly higher in cervical cancer in situ than in normal tissues. RNAi mediated suppression of LIV-1 in HeLa cells significantly inhibited cell proliferation, colony formation, migration, and invasive ability, but had no effect on cell apoptosis. Furthermore, LIV-1 suppression is accompanied by down-regulation of p44/42 MAPK, phospho-p44/42 MAPK, Snail and Slug expression levels. Hence, our data provide the first evidence that LIV-1 mRNA is overexpressed in cervical cancer in situ and is involved in invasion of cervical cancer cells through targeting MAPK-mediated Snail and Slug expression. [Copyright &y& Elsevier]