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Polyculture operations in freshwater aquaculture ponds can disrupt microbial communities. High-throughput sequencing was used to assess the impact of polyculture operations on bacterial and three sub-microeukaryote communities (fungi, zooplankton, and eukaryotic phytoplankton) in Penaeus vannamei aquaculture ponds containing oriental river prawns and giant freshwater prawns, respectively. The results showed that the bacterial community was less sensitive than the microeukaryote communities to both the polyculture activity and environmental variations. The polyculture of giant freshwater prawns rather than oriental river prawns was the primary factor affecting the beta diversity of the three sub-microeukaryote communities. This may be due to the larger biomass of the polyculture varieties of giant freshwater prawns compared with oriental river prawns. The polyculture activity of giant freshwater prawns with a higher density and that of oriental river prawns with a lower density increased the stochasticity of the community assembly of the three sub-microeukaryote communities. It also affected the topological properties of the microbial communities, including greater correlations between ecosystem elements, and reducing the correlations among zooplanktons. The eukaryotic phytoplankton was the only microbial community that could also be explained by nutrient variation (mainly the total nitrogen). This highlights the potential role of the eukaryotic phytoplankton as a suitable indicator of the effects of nutrient input into ecosystems.

Radiation-induced lung injury (RILI) is one of the most common and fatal complications of thoracic radiotherapy, whereas no effective interventions are available. Andrographolide, an active component extracted from Andrographis paniculate, is prescribed as a treatment for upper respiratory tract infection. Here we report the potential radioprotective effect and mechanism of Andrographolide on RILI. C57BL/6 mice were exposed to 18 Gy of whole thorax irradiation, followed by intraperitoneal injection of Andrographolide every other day for 4 weeks. Andrographolide significantly ameliorated radiation-induced lung tissue damage, inflammatory cell infiltration, and pro-inflammatory cytokine release in the early phase and progressive fibrosis in the late phase. Moreover, Andrographolide markedly hampered radiation-induced activation of the AIM2 inflammasome and pyroptosis in vivo. Furthermore, bone marrow-derived macrophages (BMDMs) were exposed to 8 Gy of X-ray radiation in vitro and Andrographolide significantly inhibited AIM2 inflammasome mediated-pyroptosis in BMDMs. Mechanistically, Andrographolide effectively prevented AIM2 from translocating into the nucleus to sense DNA damage induced by radiation or chemotherapeutic agents in BMDMs. Taken together, Andrographolide ameliorates RILI by suppressing AIM2 inflammasome mediated-pyroptosis in macrophage, identifying Andrographolide as a novel potential protective agent for RILI.

We report a successful field trial of real-time optical superchannel transport of 400Gb/s Ethernet client traffic over a 216-km flexible grid G.652 fiber link using 64GBaud flexible rate optical transponders. We demonstrated, for the first time, error free transport of 400 GbE client traffic over an ultra-efficient optical superchannel of $2\times 200 \text{G}$ using modulation formats DP–16QAM, DP–8QAM, and DP–QPSK. Error free performance of 400GbE ultra-efficient optical superchannel was achieved at different channel separations as narrow as 37.5 GHz for DP–16QAM, 39 GHz for DP–8QAM, and 50 GHz for DP–QPSK. We also successfully demonstrated non-contiguous 400GbE optical superchannel, where the optical sub-channels are in non-adjacent spectral slots across the whole ${C}$ -band (3.85 THz apart). Stable long term (overnight) error free optical performance and end-to-end 400 GbE full throughput were measured.

Chronic low-grade inflammation plays an important role in the pathogenesis of type 2 diabetes. Src homology 2 domain-containing tyrosine phosphatase-2 (SHP2) has been reported to play diverse roles in different tissues during the development of metabolic disorders. We previously reported that SHP2 inhibition in macrophages results in increased cytokine production. Here, we investigated the association between SHP2 inhibition in macrophages and the development of metabolic diseases. Unexpectedly, we found that mice with a conditional SHP2 knockout in macrophages (cSHP2-KO) have ameliorated metabolic disorders. cSHP2-KO mice fed a high-fat diet (HFD) gained less body weight and exhibited decreased hepatic steatosis, as well as improved glucose intolerance and insulin sensitivity, compared with HFD-fed WT littermates. Further experiments revealed that SHP2 deficiency leads to hyperactivation of caspase-1 and subsequent elevation of interleukin 18 (IL-18) levels, both in vivo and in vitro. Of note, IL-18 neutralization and caspase-1 knockout reversed the amelioration of hepatic steatosis and insulin resistance observed in the cSHP2-KO mice. Administration of two specific SHP2 inhibitors, SHP099 and Phps1, improved HFD-induced hepatic steatosis and insulin resistance. Our findings provide detailed insights into the role of macrophagic SHP2 in metabolic disorders. We conclude that pharmacological inhibition of SHP2 may represent a therapeutic strategy for the management of type 2 diabetes.

Anti-programmed death-1 (PD-1) antibody changed the treatment of non-small cell lung cancer (NSCLC), however, reliable predictive markers were lacking. We aimed to explore factors associated with response and survival, and develop predictive models. This multicenter retrospective study included a training cohort (n = 92) and validation cohort (n = 111) with NSCLC patients received anti-PD-1 antibody monotherapy in eight Chinese hospitals, and a control cohort (n = 124) with NSCLC patients received chemotherapy. Logistic and Cox models were used to identify factors associated with response and survival respectively. Nomograms were developed based on significant factors, and evaluated by Concordance-index (C-index), area under the curve (AUC) and calibration curve. In training cohort, smoking history (P = 0.027) and higher absolute lymphocyte count (P = 0.038) were associated with response. Female (P

Aberrant activation of NLRP3 inflammasome has an important function in the pathogenesis of various inflammatory diseases. Although many components and mediators of inflammasome activation have been identified, how NLRP3 inflammasome is regulated to prevent excessive inflammation is unclear. Here we show NLRP3 inflammasome stimulators trigger Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) translocation to the mitochondria, to interact with and dephosphorylate adenine nucleotide translocase 1 (ANT1), a central molecule controlling mitochondrial permeability transition. This mechanism prevents collapse of mitochondrial membrane potential and the subsequent release of mitochondrial DNA and reactive oxygen species, thus preventing hyperactivation of NLRP3 inflammasome. Ablation or inhibition of SHP2 in macrophages causes intensified NLRP3 activation, overproduction of proinflammatory cytokines IL-1β and IL-18, and increased sensitivity to peritonitis. Collectively, our data highlight that, by inhibiting ANT1 and mitochondrial dysfunction, SHP2 orchestrates an intrinsic regulatory loop to limit excessive NLRP3 inflammasome activation., The NLRP3 inflammasome is central to a variety of inflammatory diseases, but how it is regulated to prevent excessive inflammation is not clear. Here the authors show that NLRP3 activation causes SHP2 translocation to the mitochondria to interact with and dephosphorylate ANT1, thus stabilizing the mitochondria and preventing release of proinflammatory mitochondrial DNA and ROS.

Nonresolving inflammation is involved in the initiation and progression process of tumorigenesis. Src homology 2 domain-containing tyrosine phosphatase 2 (SHP2) is known to inhibit acute inflammation but its role in chronic inflammation-associated cancer remains unclear. The role of SHP2 in T cells in dextran sulfate sodium (DSS)-induced colitis and azoxymethane-DSS-induced colitis-associated carcinogenesis was examined using SHP2CD4-/- conditional knockout mice. SHP2 deficiency in T cells aggravated colitis with increased level of pro-inflammatory cytokines including IFN-γ and IL-17A. In contrast, the SHP2CD4-/- mice developed much fewer and smaller tumors than wild type mice with higher level of IFN-γ and enhanced cytotoxicity of CD8+ T cells in the tumor and peritumoral areas. At the molecular level, STAT1 was hyper-phosphorylated in T cells lacking SHP2, which may account for the increased Th1 differentiation and IFN-γ secretion. IFN-γ neutralization or IFN-γ receptor knockout but not IL-17A neutralization, abrogated the anti-tumor effect of SHP2 knockout with lowered levels of perforin 1, FasL and granzyme B. Finally, the expression of granzyme B was negatively correlated with the malignancy of colon cancer in human patients. In conclusion, these findings suggest a new strategy to treat colitis-associated cancer via targeting SHP2.

Impairment of glucose (Glu) uptake and storage by skeletal muscle is a prime risk factor for the development of metabolic diseases. Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a highly abundant RNA-binding protein that has been implicated in diverse cellular functions. The aim of this study was to investigate the function of hnRNP A1 on muscle tissue insulin sensitivity and systemic Glu homeostasis. Our results showed that conditional deletion of hnRNP A1 in the muscle gave rise to a severe insulin resistance phenotype in mice fed a high-fat diet (HFD). Conditional knockout mice fed a HFD showed exacerbated obesity, insulin resistance, and hepatic steatosis. In vitro interference of hnRNP A1 in C2C12 myotubes impaired insulin signal transduction and inhibited Glu uptake, whereas hnRNP A1 overexpression in C2C12 myotubes protected against insulin resistance induced by supraphysiological concentrations of insulin. The expression and stability of glycogen synthase (gys1) mRNA were also decreased in the absence of hnRNP A1. Mechanistically, hnRNP A1 interacted with gys1 and stabilized its mRNA, thereby promoting glycogen synthesis and maintaining the insulin sensitivity in muscle tissue. Taken together, our findings are the first to show that reduced expression of hnRNP A1 in skeletal muscle affects the metabolic properties and systemic insulin sensitivity by inhibiting glycogen synthesis.

We report successful field trial demonstration of real-time 400GbE traffic transported over optical superchannels of both conventional and non-contiguous spectral configurations using configurable modulation formats (200G DP-16QAM/DP-QPSK/DP-8QAM). Stable long term error free performance was demonstrated.

Imidazole-based task-specific ionic liquids designed to extract U(VI) from nitric acid medium were synthesized through the introduction of tributyl phosphate functional group in cationic of these ionic liquids. Their structures were confirmed by Fourier transform infrared spectrometer, nuclear magnetic resonance spectrum and element analysis. These task-specific ionic liquids can be used simultaneously as solvents and extractants for extracting U(VI) in nitric acid medium. Preliminary extraction data showed that they could be efficiently used to extract U(VI) in nitric acid medium at room temperature.

Core-shell nanocomposite particles with polystyrene sphere core and polythiophene overlayer shell were synthesized through chemical oxidative polymerization of thiophene templated using uniquely structured polystyrene latex. The morphology of polythiophene shell, which has nanorod shaped or featureless surface morphology, can be simply controlled by varying the dosage and feeding protocol of oxidizers.

To investigate roles of nitric oxide (NO) signal in accumulations of phenolic acids in abscisic.acid (ABA)-induced Salvia miltiorrhiza hairy roots, S. miltiorrhiza hairy roots were treated with different concentrations of sodium nitroprusside (SNP)-an exogenous NO donor, for 6 days, and contents of phenolic acids in the hairy roots are determined. Then with treatment of ABA and NO scavenger (2-(4-carboxy-2-phenyl)-4,4,5,5-tetramethylimidazoline-1- oxyl-3-oxide, c-PTIO) or NO synthase inhibitor (NG-nitro-L-arginine methyl ester, L-NAME), contents of phenolic acids and expression levels of three key genes involved in phenolic acids biosynthesis were detected. Phenolic acids production in S. miltiorrhiza hairy roots was most significantly improved by 100 µmoL/L SNP. Contents of RA and salvianolic acid B increased by 3 and 4 folds. ABA significantly improved transcript levels of PAL (phenylalanine ammonia lyase), TAT (tyrosine aminotransferase) and RAS (rosmarinic acid synthase), and increased phenolic acids accumulations. However, with treatments of ABA+c-PTIO or ABA+L-NAME, accumulations of phenolic acids and expression levels of the three key genes were significantly inhibited. Both NO and ABA can increase accumulations of phenolic acids in S. miltiorrhiza hairy roots. NO signal probably mediates the ABA-induced phenolic acids production.

As a first-line anti-tuberculosis drug, isoniazid has a serious adverse side effect: hepatotoxicity. Therefore, the assessment and monitoring of hepatotoxicity from isoniazid to prevent liver injury are great concerns. In this experiment, we compared the levels of ALT in plasma and DNA methylation. 30 male SD rats were allocated randomly into two groups, a control group and an isoniazid group, and treated, respectively, with pure water and isoniazid at low dosage (10 mg/(kg day)) for 42 days by oral gavage. Five rats per group were sacrificed after 14, 28, and 42 days of isoniazid treatment. The levels of methylation in the genome and LINE-1 were measured, in which hypomethylation in the whole genome and LINE-1 repetitive sequences was observed in the INH group during the later period of the experiment (the 42nd day) accompanied with pathological changes in the liver. Thus, our results suggest that low dose of isoniazid can induce liver injury and that level of DNA methylation may be a more sensitive marker for monitoring drug-induced hepatotoxicity than aminotransferase.

A series of novel furoxan-based nitric oxide (NO)-releasing derivatives of glycyrrhetinic acid (GA) were designed, synthesized, and evaluated for their in vitro cytotoxicity against human hepatocellular carcinoma (HCC) and non-tumor liver cells. Five furoxan/GA hybrids, 7b–d, 7f, and 7g, displayed potent cytotoxicity against HCC cells (IC50: 0.25–1.10 μM against BEL-7402 cells and 1.32–6.78 μM against HepG2 cells), but had a little effect on the growth of LO2 cells, indicating that these compounds had selective cytotoxicity against HCC cells. Furthermore, these compounds produced high concentrations of NO in HCC cells, but low in LO2 cells and treatment with hemoglobin partially reduced the cytotoxicity of the hybrid in HCC cells. Apparently, the high concentrations of NO produced by NO donor moieties and the bioactivity of GA synergistically contribute to the cytotoxicity, but the NO is a major player against HCC cells in vitro. Potentially, our findings may aid in the design of new chemotherapeutic reagents for the intervention of human HCC at clinic.

In a lab-scale continuously running fermentative hydrogen producing membrane bioreactor (HPMBR), the properties of biomass, extracellular polymeric substances (EPS) and colloidal material in the mixed liquor along with their influence on the performance of submerged hollow-fiber membrane modules were investigated. Five experimental runs were conducted at organic loading rates (OLRs) of 4.0, 6.0, 13, 22 and 30 g COD L −1 d −1 . As OLR increased, the biomass content, colloidal hydrophobicity and mean particle diameter increased. Additionally, the membrane fouled more rapidly as OLR increased. The bound and soluble EPS content of biomass in the HPMBR were higher than that found in a hydrogen producing system in CSTR mode and in an aerobic activated sludge system. At a constant permeate flux rate of 11.1 L min −1 m −2 and N2 sparging intensity of 4.26 L min −1 m −2 , membrane fouling was characterized by two distinct stages: an initial stage characterized by a relatively faster fouling rate and a second stage where the fouling rate was slower. Both fouling rates increased with increased biomass concentration and colloidal zeta potential. Increases in pore clogging resistance Rcoll correlated to increased concentrations of colloidal proteins and polysaccharides. The observed relationships between the membrane fouling properties and the properties of biomass and colloids (including soluble EPS), accompanied by scanning electron and confocal microscopy examination of the fouled membrane surfaces suggest that colloid adhesion and biomass deposition were the two dominant membrane fouling mechanisms in the HPMBR system.

Purpose : To compare the outcomes of spinal anesthesia in obese and non-obese patients. Methods : In this study, 199 patients who underwent total knee replacement arthroplasty (TKRA) were categorized into obesity group (n = 61) and non-obesity group (n = 138). Anesthesia was considered successful if a bilateral T12 sensory blockage occurred within the first 15 min of injection of intrathecal drug. Parameters that influence spinal anesthesia were analyzed using logistic regression by means of multiple variables that independently influence the outcome of spinal anesthesia. Results : It was observed that the independent predictors for successful anesthesia in the patients were dose of bupivacaine (odds ratio at 95 % confidence interval = 2.08; range: 1.61 - 2.67) and obesity status (odds ratio at 95 % confidence interval = 2.83; range: 1.21 - 6.49). The outcome of the multivariate analysis also indicated that the dose of bupivacaine, body mass index (BMI) and obesity were predictors of spinal anesthesia. It was also found that the period of the sensory blockage due to bupivacaine was longer in the obesity group than in the non-obesity group. Conclusion : Sensory blockage in bupivacaine anesthesia during TKRA is influenced by dose of bupivacaine, obesity and BMI. Keywords : Spinal anesthesia, Total knee replacement arthroplasty, Bupivacaine, Obesity, Body mass index, Logistic regression

Glial cell line-derived neurotrophic factor (GDNF), a protein of the transforming growth factor-β (TGF-β) superfamily, was initially cloned and purified from the B49 glial cell line 1. As a potent neurotrophic factor, GDNF promotes the survival of central dopaminergic 1–3, noradrenergic 4 as well as motor neurons 5, 6. Moreover, GDNF enhances striatal neurogenesis after stroke 7–9. Efforts have been made to deliver exogenous GDNF directly into the brain 10–12, by adenoviral vector 13, or by gene-modified mesenchymal stem cells 14 in different models of cerebral ischemia, and the efficacy of GDNF treatment of experimental stroke has been well established. Animals receiving GDNF have smaller infarct volume, less severe cerebral edema, and a reduced number of apoptotic cells in the penumbral zone 14–16. GDNF expression is low in normal adult rat brain, but can be up-regulated by a variety of central nervous system (CNS) insults including focal brain ischemia 17–20. Taken together, these data suggest that manipulation of endogenous GDNF levels may facilitate the self-repair efforts of the brain against ischemic attack, and therefore, could be a new target in the treatment of stroke. Intravenous transplantation of bone marrow stromal cells (BMSCs) ameliorates functional deficits in rodent cerebral ischemia models 21–23 as well as in stroke patients 24. BMSCs are a heterogeneous subpopulation of bone marrow cells including mesenchymal stem and progenitor cells. Although these cells can release a variety of neurotrophic factors in response to ischemic environment 25–27, the limited number of BMSCs in the brain raises doubt about the importance and weight of factors secreted by BMSC per se in the process of functional recovery. Being the most abundant cells in the brain, astrocytes provide many supportive activities essential for neuronal function under physiological circumstances 28, 29. After various insults, local astrocytes undergo cellular hypertrophy, hyperplasia and become “reactive”. Reactive astrocytes promote brain plasticity and recovery from stroke, and the beneficial effects of reactive astrocytes are enhanced in the ischemic brain after BMSC transplantation 30–32. In the present study, we hypothesize that BMSCs in the penumbral zone activate local astrocytes, the latter release large amount of GDNF, which contributes to the functional improvement.

The influence of organic loading rates (OLRs) on the performance of fermentative hydrogen-producing bioreactors operating in continuous stirred tank reactor (CSTR) and membrane bioreactor (MBR) modes was examined. Five OLRs were examined, ranging from 4.0 to 30 g COD L −1 d −1 , with influent glucose concentrations ranging from 1.3 to 10 g COD L −1 . At OLRs up to 13 g COD L −1 d −1 , all influent glucose was utilized and the H 2 yield was not significantly influenced by OLR, although the yield in the CSTR mode was significantly higher than that in the MBR mode, 1.25 versus 0.97 mol H 2 (mol Gluc. Conv.) −1 , respectively. At an OLR of 30 g COD L −1 d −1 , both reactor modes were overloaded with respect to glucose utilization and also had significantly higher H 2 yields of 1.77 and 1.49 mol H 2 (mol Gluc. Conv.) −1 for the CSTR and MBR modes, respectively, versus the underloaded operation. At the intermediate OLR of 22 g COD L −1 d −1 , the H 2 yield was maximized at 1.78 mol H 2 (mol Gluc. Conv.) −1 for both the CSTR and MBR operation. Overall H 2 production was 50% higher in the MBR mode, 0.78 versus 0.51 moles d −1 , because the CSTR mode was overloaded with respect to glucose utilization at this OLR. These results suggest that an optimum OLR that maximizes H 2 yield and H 2 production may be near the OLR that causes overload with respect to substrate utilization. Additionally, while the CSTR mode is easier to operate and provides higher H 2 yields at underloaded and overloaded OLRs, the MBR mode may be preferable when operating near the optimum OLR.

Transplantation of bone marrow stromal cells (BMSCs) improves animal neurological functional recovery after stroke. To obtain insight into the mechanisms underlying the therapeutic benefit, we directed our attention to the interaction of BMSCs with astrocytes. Astrocytes become reactive (astrogliosis) after a brain injury, such as stroke. Astrogliosis plays both beneficial and detrimental roles in brain recovery. Previously, we have shown that administration of BMSCs to animals with stroke significantly reduces the thickness of the scar wall formed by reactive astrocytes. We tested the influence of mouse bone marrow stromal cell (mBMSC) on astrogliosis under oxygen-glucose deprivation (OGD)/reoxygenation conditions in vitro, employing an anaerobic chamber. Our data indicate that mBMSCs down-regulate glial fibrillary acidic protein (GFAP) expression in astrocytes after 2 h of OGD and an additional 16 h reoxygenation. mBMSCs protected astrocytes from ischemia, maintaining morphological integrity and proliferation. The IL-6/IL-6R/gp130 pathway is associated with astrogliosis in response to CNS (disorders. Therefore, we examined the effects of mBMSC on the IL-6/IL-6R/gp130 pathway as an underlying mechanism of mBMSC-altered astrogliosis. Furthermore, IL-6 siRNA was used to block IL-6 expression in astrocytes to further investigate IL-6 involvement in mBMSC-altered astrogliosis. Our results indicate that the mBMSC-conferred decline of astrogliosis post-ischemia may derive from the down-regulation of the IL-6/IL-6R/gp130 pathway.

We provide a new central limit theorem (CLT) for spatial processes under weak conditions that are plausible for many economic applications in which location is endogenous. In particular, our CLT is designed for problems that have some, but not necessarily all, of the following features: (i) Agents choose the locations of observations to maximize profits, welfare, or some other objective. (ii) The objects that are chosen (e.g., stores or brands) interact with one another. For example, they can be substitutes or complements. (iii) Interaction can be complex. In particular, interaction between i and j need not depend only on the distance between the locations of i and j, but can also depend on distance to or location of other observations k, or possibly on the number of other such observations.

Treatment of rodents after stroke with bone marrow stromal cells (BMSCs) improves functional outcome. However, the mechanisms underlying this benefit have not been ascertained. This study focused on the contribution of neurotrophic and growth factors produced by BMSCs to therapeutic benefit. Rats were subjected to middle cerebral artery occlusion and the ischemic brain extract supernatant was collected to prepare the conditioned medium. The counterpart normal brain extract from non-ischemic rats was employed as the experimental control. Using microarray assay, we measured the changes of the neurotrophin associated gene expression profile in BMSCs cultured in different media. Furthermore, real-time RT-PCR and fluorescent immunocytochemistry were utilized to validate the gene changes. The morphology of BMSCs, cultured in the ischemic brain-conditioned medium for 12 h, was dramatically altered from a polygonal and flat appearance to a fibroblast-like long and thin cell appearance, compared to those in the normal brain-conditioned medium and the serum replacement medium. Forty-four neurotrophin-associated genes in BMSCs were identified by microarray assay under all three culture media. Twelve out of the 44 genes (7 neurotrophic and growth factor genes, 5 receptor genes) increased in BMSCs cultured in the ischemic brain-conditioned medium compared to the normal brain-conditioned medium. Real time RT-PCR and immunocytochemistry validated that the ischemic brain-conditioned medium significantly increased 6/7 neurotrophic and growth factor genes, compared with the normal brain-conditioned medium. These six genes consisted of fibroblast growth factor 2, insulin-like growth factor 1, vascular endothelial growth factor A, nerve growth factor beta, brain-derived neurotrophic factor and epidermal growth factor. Our results indicate that transplanted BMSCs may work as ‘small molecular factories’ by secreting neurotrophins, growth factors and other supportive substances after stroke, which may produce therapeutic benefits in the ischemic brain.

In many spatial applications, agents make discrete choices (e.g. operating or product-line decisions), and applied researchers need econometric techniques that enable them to model such situations. Unfortunately, however, most discrete-choice estimators are invalid when variables and/or errors are spatially dependent. More generally, discrete-choice estimators have difficulty dealing with many common problems such as heteroskedasticity, endogeneity, and measurement error, which render them inconsistent, as well as the inclusion of fixed effects in short panels, which renders them computationally burdensome if not infeasible. In this paper, we introduce a new estimator that can be used to overcome many of the above-mentioned problems. In particular, we show that the one-step (‘continuous updating’) GMM estimator is consistent and asymptotically normal under weak conditions that allow for generic spatial and time series dependence. We use our estimator to study mine operating decisions in a real-op...

We evaluated the effects of allogeneic bone marrow stromal cell treatment of stroke on functional outcome, glial–axonal architecture, and immune reaction. Female Wistar rats were subjected to 2 h of middle cerebral artery occlusion. Rats were injected intravenously with PBS, male allogeneic ACI – or syngeneic Wistar –bone marrow stromal cells at 24 h after ischemia and sacrificed at 28 days. Significant functional recovery was found in both cell-treated groups compared to stroke rats that did not receive BMSCs, but no difference was detected between allogeneic and syngeneic cell-treated rats. No evidence of T cell priming or humoral antibody production to marrow stromal cells was found in recipient rats after treatment with allogeneic cells. Similar numbers of Y-chromosome+ cells were detected in the female rat brains in both groups. Significantly increased thickness of individual axons and myelin, and areas of the corpus callosum and the numbers of white matter bundles in the striatum were detected in the ischemic boundary zone of cell-treated rats compared to stroked rats. The areas of the contralateral corpus callosum significantly increased after cell treatment compared to normal rats. Processes of astrocytes remodeled from hypertrophic star-like to tadpole-like shape and oriented parallel to the ischemic regions after cell treatment. Axonal projections emanating from individual parenchymal neurons exhibited an overall orientation parallel to elongated radial processes of reactive astrocytes of the cell-treated rats. Allogeneic and syngeneic bone marrow stromal cell treatment after stroke in rats improved neurological recovery and enhanced reactive oligodendrocyte and astrocyte related axonal remodeling with no indication of immunologic sensitization in adult rat brain.

Bolted ring-type splices are very common in guyed communication towers using solid round legs 65 mm in diameter or smaller, but there is no guidance provided in either the Canadian Institute of Steel Construction Handbook of steel construction or the American Institute of Steel Construction Manual of steel construction for the design of such splices. Eighteen ring-type splices (three groups of six specimens each) were tested and experimental failure loads were determined. Based on the test results, it is concluded that it is unsafe to ignore the eccentricity of the splice. It is suggested that the load at first yield be conservatively taken as the strength of the splice. A simplified design method is proposed that takes into account the eccentricity of the splice, and the results from the proposed method agree closely with the experimental values.Key words: eccentricity of splice, guyed towers, ring-type splice, solid round legs, tensile strength.

Background and aims To find new diagnostic markers to monitor isoniazid-induced liver injury. Methods SD rats were treated with low dosage of isoniazid and the light microscopic findings of livers were collected. The methylation status of cytochrome p450 2E1 promoter was determined. Results Cell edema and spotty necrosis on liver cells appeared in the experimental group and promoter methylation of cytochrome p450 2E1 was detected. Conclusions Low-dosage isoniazid can induce liver injury.

The dentate gyrus is one of the few areas of the mammalian brain where new neurons are continuously produced in adulthood. Recent studies demonstrated that dentate neurogenesis increased after transient global ischemia and it is suggested that the increased neurogenesis contributes to the recovery of hippocampal function. In the present study, adult Mongolian gerbils were chronically treated with ginsenoside Rg1 after ischemia, and the proliferation of cells in the dentate gyrus was examined. It was proved that bromodeoxyuridine (BrdU)-labeled cells in the dentate gyrus were significantly enhanced in number following Rg1 treatment after 6 min global ischemia. In addition, the number of surviving BrdU-positive cells 40 days after ischemia also increased markedly in the Rg1 group. This suggests that ginsenoside Rg1 delivered to the brain well after stroke may have therapeutic benefits.

Exploration of the SAR around selective NK 2 antagonists, SR48968 and ZD7944, led to the discovery that naphth-1-amide analogues provide potent dual NK 1 and NK 2 antagonists. ZD6021 inhibited binding of [ 3 H]-NKA or [ 3 H]-SP to human NK 1 and NK 2 receptors, with high-affinity ( K i =0.12 and 0.62 nM, respectively). In functional assays ZD6021 had, at 10 −7 M, in human pulmonary artery p K B =8.9 and in human bronchus p K B =7.3, for NK 1 and NK 2 , respectively. Oral administration of ZD6021 to guinea pigs dose-dependently attenuated ASMSP induced extravasation of plasma proteins, ED 50 =0.5 mg/kg, and NK 2 mediated bronchoconstriction, ED 50 =13 mg/kg.

Relevance and Coherence Abstract: As a tool for communication, language is unique for human beings. In some context, the speakers and listeners construct and comprehend the same text in different ways. In order to have a successful communication, they have to know the appropriate ways to express and the exact information they want to convey. In the process of discourse interpretation, Coherence and relevance are two main factors. This paper aims to investigate discourse coherence in terms of relevance and analyze the relations between the two.

To establish HP14.5 cell line stably expressing hepatitis B virus X (HBx) and detect the effect of HBx on cell proliferation, cell cycle and the wnt/β-catenin signal pathway of hepatic progenitor cells.The plasmid of pSEB-Flag-HBx and the packaging plasmid pAmpho were co-transfected into HEK 293T cells to construct the recombinant retrovirus carrying HBx gene. The recombinant retrovirus wan then transfected into mouse hepatic progenitor cells HP14.5. The blasticidin-resistant clones of HBx cells (HP14.5/HBx) were selected out and cultured as the experimental group, paralleled with the vector control HP14.5/Rv (HP14.5/pSEEB-Flag) and HP14.5 cell as negative control. The cell proliferation was tested by MTS assay, the cell cycle was measured by flow cytometry, the expression levels of cyclin D1 and c-myc mRNA were tested by real time PCR, and the expression leveIs of HBx, cyclin D1, c-myc, GSK3β, p-GSK3β (ser-9), β-catenin proteins were examined by Western blotting.The expression of HBx at both mRNA and protein levels was positive in HP14.5/HBx cell line as confirmed by RT-PCR and Western blotting. Compared with the control groups, the proliferation of HP14.5/HBx cells increased significantly (P0.05), and the expression level of cyclin D1 and c-myc mRNA rose significantly(P0.05). G1-phase cell proportion was reduced while the proportion in S and G2 phases went up significantly (P0.05). The expression levels of cyclin D1, c-myc, β-catenin and p-GSK3β (ser-9) proteins increased significantly (P0.05)except GSK3β (P0.05).The hepatic stem cell line stably expressing HBx has been constructed successfully. HBx can promote the proliferation and malignant transformation of hepatic stem cells via the activation of Wnt/β-catenin signal pathway.

Relevance Theory's unique view about context is cognitive context, which is dramatically different from the traditional view on context. Cognition varies with each individual so different people will produce different texts even though they are in the same social and cultural context. This paper is dedicated to the studies of cognitive context's role in discourse production.

To investigate the epithelial-mesenchymal transition (EMT) function of HBx in hepatic progenitor cells (HPCs).The plasmids of pSEB-Flag-HBX and the packaging plasmids pAmpho were co-transfected in HEK 293T cells, and the recombinant retroviruses carrying HBx gene generated from the cell line were used to infect mouse HPCs HP14.5. We screened HP14.5 cells which stably expressed HBx by blasticidin to observe the morphological changes and investigate the epithelial and mesenchymal markers by real-time PCR and Western blotting. The metastatic capacity of HPCs infected with HBx was evaluated by wound-healing assay.HP14.5 cells with stable expression of HBx protein suffered morphological changes from polygonal to a spindle-like shape. The expressions of neural cadherin (N-cadherin), Snail and vimentin at both protein and mRNA levels significantly increased (P0.05), but epithelial cadherin (E-cadherin) and cytokeratin-18 (CK18) decreased (P0.05). In addition, the migratory potential was enhanced in HP14.5 cells infected with HBx.HBx can induce EMT and enhance the migratory potential of HPCs.

One of the main functions of language is to convey meaning between human beings, so how to use and interpret language appropriately is very important in communication. According to the dynamic study of context, firstly, this thesis discusses how language users actively manipulate aspects of context and produce favourable context to attain their communicative goals. It concentrates on the relations between cognitive context strucrization factors and discourse production. As different individuals in the society, such different factors as different cognitive ability, different educational and cultural backgrounds and different experiences in the social life will affect individual’s cognitive context and discourse interpretation.

Text and context are two essential elements in human communication. Text can not exist in a vacuum. Its production and comprehension are influenced and restricted by context. This paper aims to analyze the relations between context and text with the framework of both traditional context and cognitive context by Sperber & Wilson.

Increasing evidence has shown that normal stem cells may contribute to the development and progression of cancer by acting as cancer-initiating cells. The hepatitis B virus X (HBX) protein has been implicated in the hepatitis B virus (HBV)-associated liver carcinogenesis. However, the role of HBX in hepatic progenitor cells (HPCs) is poorly understood. In this study, we aimed to determine the role of HBX in regulating HPC proliferation and differentiation. Using MTT analysis, we showed that HPCs infected with adenovirus expressing HBX (Ad-HBX) grew more rapidly compared to HPCs infected with adenovirus expressing green fluorescent protein (Ad-GFP). To reveal the mechanism for the increased cell number after HBX treatment, we searched for possible alterations in the cell cycle and apoptosis by flow cytometry. We found that HBX treatment resulted in an increase in the S phase cell cycle fraction and a decrease in apoptosis. In addition, we examined the differentiation of HPCs infected with Ad-HBX and found that the HBX expression in HP14.5 cells led to an increased expression of early progenitor markers and a decreased expression of late hepatocyte markers. Furthermore, HBX inhibited glycogen synthesis in HP14.5 cells, indicating that HBX is capable of inhibiting terminal hepatic differentiation. Therefore, our results strongly suggest that HBX plays an important role in regulating HPC proliferation and differentiation. This is the potential mechanism of HBX-mediated liver carcinogenesis.

The molecular mechanisms underlying cerebral angiogenesis have not been fully investigated. Using primary mouse brain endothelial cells (MBECs) and a capillary-like tube formation assay, we investigated whether the sonic hedgehog (Shh) signaling pathway is coupled with the plasminogen/plasmin system in mediating cerebral angiogenesis. We found that incubation of MBECs with recombinant human Shh (rhShh) substantially increased the tube formation in naïve MBECs. This was associated with increases in tissue plasminogen activator (tPA) activation and reduction of plasminogen activator inhibitor 1 (PAI-1). Blockage of the Shh pathway with cyclopamine abolished the induction of tube formation and the effect of rhShh on tPA and PAI-1. Addition of PAI-1 reduced rhShh-augmented tube formation. Genetic ablation of tPA in MBECs impaired tube formation and downregulated of vascular endothelial growth factor (VEGF) and angiopoietin 1 (Ang1). Addition of rhShh to tPA-/- MBECs only partially restored the tube formation and upregulated Ang1, but not VEGF, although rhShh increased VEGF and Ang1 expression on wild-type MBECs. Complete restoration of tube formation in tPA-/- MBECs was observed only when both exogenous Shh and tPA were added. The present study provides evidence that tPA and PAI-1 contribute to Shh-induced in vitro cerebral angiogenesis.

We investigated whether compensatory reinnervation in the corticospinal tract (CST) and the corticorubral tract (CRT) is enhanced by the administration of bone marrow stromal cells (BMSCs) after experimental stroke. Adult male Wistar rats were subjected to permanent right middle cerebral artery occlusion (MCAo). Phosphate-buffered saline (PBS, control, n=7) or 3x10(6) BMSCs in PBS (n=8) were injected into a tail vein at 1 day postischemia. The CST of the left sensorimotor cortices was labeled with DiI 2 days prior to MCAo. Functional recovery was measured. Rats were sacrificed at 28 days after MCAo. The brain and spinal cord were removed and processed for vibratome sections for laser-scanning confocal analysis and paraffin sections for immunohistochemistry. Normal rats (n=4) exhibited a predominantly unilateral pattern of innervation of CST and CRT axons. After stroke, bilateral innervation occurred through axonal sprouting of the uninjured CRT and CST. Administration of BMSCs significantly increased the axonal restructuring on the de-afferented red nucleus and the denervated spinal motoneurons (p0.05). BMSC treatment also significantly increased synaptic proteins in the denervated motoneurons. These results were highly correlated with improved functional outcome after stroke (r0.81, p0.01). We conclude that the transplantation of BMSCs enhances axonal sprouting and rewiring into the denervated spinal cord which may facilitate functional recovery after focal cerebral ischemia.