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Controlled synthesis of Au(I)–3-mercaptopropionic acid (MPA) nanostructures with diverse morphologies, such as quasi-rectangular nanosheets, quasi-square nanosheets, nanobelts, nanostrings and nanochips, were successfully achieved. Regulating the morphology of Au(I)–MPA nanostructures was realized by reverse microemulsion, which not only has a confinement effect on the size but also directs their assembly into different morphologies. In addition, adjustment of the electrostatic interaction between ligands induces consecutive responses in Au(I)–Au(I) interaction and Au–S coordination, and also results in distinct morphology transformation. Taking advantage of the structural characteristics of the obtained Au(I)–MPA nanostructures, they are used as ideal precursors for the preparation of Au particles and photoluminescent Au clusters. This work not only provides effective strategies for the morphology regulation of coordination polymer nanostructures but also extends their application.

Sirtuin 2 (SIRT2) is a member of the sirtuin family. Previous studies have suggested that SIRT2 mediates the cell death in models of Parkinson's disease and Huntington's disease. However, the role of SIRT2 in oxidative stress-induced cell death has remained unclear. In this study, we investigated the roles of SIRT2 in oxidative stress-induced cell death using differentiated PC12 cells as a cell model. We found that H2O2 induced a significant increase in the SIRT2 level in the cells. Both SIRT2 silencing and the SIRT2 inhibitor AGK2 significantly decreased H2O2-induced apoptosis, partially by inhibiting caspase-3 activation. We further found that silencing of SIRT2 led to decreased reactive oxygen species levels in the H2O2-treated cells. Collectively, our observations have suggested that SIRT2 plays a significant role in oxidative stress-induced cell death.

Ethnopharmacological relevance Extracts from Ginkgo biloba L. leaves confer their therapeutic effects through the synergistic actions of flavonoid and terpenoid components, but some non-flavonoid and non-terpenoid components also exist in this extract. In the study of this paper, an investigation was carried out to compare the pharmacokinetic parameters of fourteen compounds to clarify the influences of non-flavonoid and non-terpenoid fraction (WEF) on the pharmacokinetics profile of the flavonoid fraction (FF) and the terpene lactone fraction (TLF) from Ginkgo biloba extracts. Materials and methods A selective and sensitive UPLC–MS/MS method was established to determine the plasma concentrations of the fourteen compounds to compare the pharmacokinetic parameters after orally administration of FF, TLF, FF–WEF, FF–TLF, TLF–WEF and FF–TLF–WEF with approximately the same dose. At different time points, the concentration of rutin (1), isoquercitrin (2), quercetin 3-O-[4-O-(-β-D-glucosyl)-α-L-rhamnoside] (3), ginkgolide C (4), bilobalide (5), quercitrin (6), ginkgolide B (7), ginkgolide A (8), luteolin (9), quercetin (10), apigenin (11), kaempferol (12), isorhamnetin (13), genkwanin (14) in rat plasma were determined and main pharmacokinetic parameters including T1/2, Tmax, Cmax and AUC were calculated using the DAS 3.2 software package. The statistical analysis was performed using the Student׳s t-test with P Results FF and WEF had no effect on the pharmacokinetic behaviors and parameters of the four terpene lactones, but the pharmacokinetic profiles and parameters of flavonoids changed while co-administered with non-flavonoid components. It was found that Cmax and AUC of six flavonoid aglycones in group FF–WEF, FF–TLF and FF–TLF–WEF had varying degrees of reduction in comparison with group FF, especially in group FF–TLF–WEF. On the contrary, the values of Cmax, Tmax and AUC of four flavonoid glycosides in group FF–TLF–WEF were significantly increased compared with those in group FF. Conclusions These results indicate that non-flavonoid components in Ginkgo biloba extracts could increase the absorption and improve the bioavailability of flavonoid glycosides but decrease the absorption and reduce the bioavailability of flavonoid aglycones.

Two types of carbon dots (C dots) exhibiting respective excitation-independent blue emission and excitation-dependent full-color emissions have been synthesized via a mild one-pot process from chlo...

It is necessary to investigate the mechanisms underlying ATP release from neural cells, because extracellular ATP plays multiple important biological roles in the brain. CD38 is an ectoenzyme that consumes NAD(+) to produce cyclic ADP-ribose (cADPR), a potent agonist of ryanodine receptors. Our previous study showed that CD38 reductions led to microglial apoptosis. In this study, we used both murine microglial BV2 cells and primary microglial cultures as cellular models to test our hypothesis that basal CD38/cyclic ADP-ribose (CD38/cADPR)-dependent signaling plays a key role in ATP release, which mediates basal survival of microglia. We found that inhibition of CD38/cADPR-dependent signaling by CD38 silencing or 8-Bromo-cADPR, a ryanodine receptor antagonist, produced significant ATP release from BV2 microglia. Cx43 small interfering RNA and Cx43 hemichannel blocker 18-α-glycyrrhetinic acid completely prevented the CD38 silencing or 8-Bromo-cADPR-induced ATP release. Prevention of the ATP release could also be due to P2X7 receptor antagonists. Our study has further suggested a key role of ATP release in the microglial apoptosis induced by decreased CD38/cADPR-dependent signaling. In addition, by using primary microglial cultures, we found that 8-Bromo-cADPR also induced significant ATP release, which could be attenuated by 18-α-glycyrrhetinic acid. 8-Bromo-cADPR was also found to induce death of primary microglial cultures. In conclusion, our results have suggested novel roles of basal activation of CD38/cADPR-dependent signaling in mediating microglial functions and survival: It mediates ATP release from microglia by modulating Cx43 hemichannels, which can significantly affect microglial survival.

Nicotinamide adenine dinucleotide (NAD(+)) plays critical roles in not only energy metabolism and mitochondrial functions, but also calcium homeostasis and immunological functions. It has been reported that NAD(+) administration can reduce ischemic brain damage. However, the mechanisms underlying the protective effects remain unclear. Because mitochondrial impairments play a key role in the cell death in cerebral ischemia, in this study we tested our hypothesis that NAD(+) can decrease mitochondrial damage-induced cell death using differentiated PC12 cells as a cellular model. We found that NAD(+) can decrease both early-stage and late-stage apoptosis, as well as necrosis of rotenone-treated PC12 cells, as assessed by FACS-based Annexin V/AAD assay. We also found that NAD(+) treatment can restore the intracellular NAD(+) levels of the rotenone-treated cells. Moreover, NAD(+) treatment can prevent rotenone-induced mitochondria depolarization. In summary, our study has provided first direct evidence that NAD(+) treatment can prevent rotenone-induced apoptosis and necrosis. Our study has also indicated that NAD(+) treatment can prevent mitochondrial damage-induced cell death, which may at least partially result from its protective effects on rotenone-induced mitochondrial depolarization. Because both mitochondrial damage and apoptosis play key roles in multiple neurological disorders, our study has highlighted the therapeutic potential of NAD(+) for brain ischemia and other neurological diseases.

Two new coumarins 7-O-(6-O-(5-O-3,4,5-tri-methoxycinnamate-β-d-apiofuranosyl-β-d-glucopyranosyl)-6-methoxy coumarin (1) and 7-O-(6-O-(4-(2-hydroxy-1-hydroxymethyl-ethoxy)-3-methoxy-cinnamyl)-β-d-glucopyranosyl)-6-methoxy coumarin (2), along with 10 known metabolites, were isolated from the bark of Streblus indicus, their structures were identified by comparison of experimental and published spectroscopic data. (S)-marmesinin (6) and scoparone (7) exhibited moderate antimicrobial activity in vitro against Staphylococcus aureus strain with the MIC values of 62.5 and 125.0 μg/mL, respectively. Betulinic acid showed inhibitory activity in vitro against MCF-7 cell with IC50 value of 9.5 ± 0.1 μM.

Hepatitis B virus (HBV) replicates its DNA genome through reverse transcription of a viral RNA pregenome. We report herein that the interferon (IFN) stimulated exoribonuclease gene of 20 KD (ISG20) inhibits HBV replication through degradation of HBV RNA. ISG20 expression was observed at basal level and was highly upregulated upon IFN treatment in hepatocytes, and knock down of ISG20 resulted in elevation of HBV replication and attenuation of IFN-mediated antiviral effect. The sequence element conferring the susceptibility of HBV RNA to ISG20-mediated RNA degradation was mapped at the HBV RNA terminal redundant region containing epsilon (ε) stem-loop. Furthermore, ISG20-induced HBV RNA degradation relies on its ribonuclease activity, as the enzymatic inactive form ISG20D94G was unable to promote HBV RNA decay. Interestingly, ISG20D94G retained antiviral activity against HBV DNA replication by preventing pgRNA encapsidation, resulting from a consequence of ISG20-ε interaction. This interaction was further characterized by in vitro electrophoretic mobility shift assay (EMSA) and ISG20 was able to bind HBV ε directly in absence of any other cellular proteins, indicating a direct ε RNA binding capability of ISG20; however, cofactor(s) may be required for ISG20 to efficiently degrade ε. In addition, the lower stem portion of ε is the major ISG20 binding site, and the removal of 4 base pairs from the bottom portion of ε abrogated the sensitivity of HBV RNA to ISG20, suggesting that the specificity of ISG20-ε interaction relies on both RNA structure and sequence. Furthermore, the C-terminal Exonuclease III (ExoIII) domain of ISG20 was determined to be responsible for interacting with ε, as the deletion of ExoIII abolished in vitro ISG20-ε binding and intracellular HBV RNA degradation. Taken together, our study sheds light on the underlying mechanisms of IFN-mediated HBV inhibition and the antiviral mechanism of ISG20 in general., Author summary HBV is a DNA virus but replicates its DNA via retrotranscription of a viral RNA pregenome. ISG20, an antiviral RNase induced by interferons, inhibits the replication of many RNA viruses but the underlying molecular antiviral mechanism remains elusive. Since all the known viruses, except for prions, have RNA products in their life cycles, ISG20 can be a broad spectrum antiviral protein; but in order to distinguish viral RNA from host RNA, ISG20 may have evolved to recognize virus-specific signals as its antiviral target. We demonstrated herein that ISG20 selectively binds to a unique stem-loop structure called epsilon (ε) in all HBV RNA species and degrades viral RNA to inhibit HBV replication. Because ε is the HBV pregenomic RNA packaging signal and reverse transcription priming site, the binding of ISG20 to ε, even in the absence of ribonuclease activity, results in antiviral effect to prevent DNA replication due to preventing viral polymerase binding to pgRNA. We also determined the structure and sequence requirements of ε RNA and ISG20 protein for ISG20-ε binding and antiviral activity. Such information will aid the function study of ISG20 against viral pathogens in host innate defense, and ISG20 has potentials to be developed into a therapeutic agent for viral diseases including hepatitis B.

To observe the effect of rhynchophylline on methamphetamine-dependent zebrafish and explore the possible mechanism.Zebrafish were divided into control group, amphetamine group, low- (50 mg/kg) and high (100 mg/kg)-dose rhynchophylline groups, and ketamine (150 mg/kg) group. Conditioned place preference (CPP) was induced in zebrafish with methamphetamine, and the staying time in the drug box and the tracking map of the zebrafish were observed with Noldus Ethovision XT system. The protein expressions of TH, NR2B and GLUR2 in the brain of zebrafish with CPP were detected with Western blotting.Compared with the control group, zebrafish in methamphetamine group showed significant variations in the staying time and swimming distance in the drug box after conditioning (P0.05) with obvious alterations of NR2B, TH and GLUR2 expressions in the brain (P0.05). Treatment of methamphetamine-dependent zebrafish with high-dose rhynchophylline significantly reduced the variations in the staying time and swimming distance in the drug box (P0.05) and in the expressions of NR2B, TH and GLUR2 in the brain (P0.05).Rhynchophylline can inhibit methamphetamine dependence in zebrafish, the mechanism of which may involve the expressions of TH, NR2B and GLUR2 proteins in the brain.

Deep learning methods have been successfully used in many areas of computer vision, including super resolution. However, all of the previous deep learning methods have been proposed for generic image super resolution. In this paper, we proposed to use convolutional neural network for face hallucination (FH) by combining the domain specific prior knowledge of face images and properties of deep learning. In the proposed method, an end to end mapping is learned as a deep convolutional network between the low resolution (LR) images and their corresponding high resolution (HR) images to upscale the input face image directly. In order to achieve larger magnification factor, we consider to cascade several convolution neural networks each of which is with a fixed up-scaling factor and upscales the LR image step by step. Experimental result shows that our proposed method can achieve better performance comparing to the traditional face hallucination methods.

A pair of enantiomers and a pair of 2,3-dihydro-1H-indene epimers, rac-indidene A (rac-1), indidenes B and C (2, 3); four new coumarin glucosides (4–7); and four known coumarin glucosides (8–11) were isolated from the bark of Streblus indicus (Bur.) Corner. The structures of 1–11 were defined by physical data analyses, including MS, NMR, and single-crystal X-ray diffraction. The absolute configurations of the 2,3-dihydro-1H-indene derivatives were defined via experimental and calculated ECD data. rac-Indidene A and indidenes B and C showed inhibitory activity against A549 and MCF-7 tumor cells with IC50 values in the range of 2.2 ± 0.1 to 7.2 ± 0.9 μM.

Fast tool servo is increasing applied to manufacture optical freeform surfaces, which are adopted in aerospace, imaging, bioengineering, energy fields to improve the performance of the system, simplify the structure of the system and lower cost. The existing FTS have limited stroke and bandwidth. FTS driven by electromagnetic force is discussed. The analysis of the magnetic circuit, the requirements of the system and the corresponding design parameters are studied. The designed FTS can realize the bandwidth of 0-100kHz with a special designed driver.

Neuronal fractalkine acts via its receptor, CX3CR1, on microglia to regulate neuroinflammation. Conflicting results have been reported in studies employing CX3CR1 deficient ( Cx3cr1 −/− ) mice. Here, compared to wild-type, endotoxin-treated neuron-glial Cx3cr1 −/− cultures produced less TNF-α, nitric oxide and superoxide; however, fractalkine treatment inhibited the release of pro-inflammatory factors in wild-type and BV-2 cell cultures. Furthermore, endotoxin-treated BV-2 cells expressing siRNA against CX3CR1 increased nitric oxide and TNF-α production. We hypothesize that CX3CL1-CX3CR1 signaling is neuroprotective and propose that the reduced production of pro-inflammatory signals in Cx3cr1 −/− microglia may result from compensatory mechanisms and not be the direct result of CX3CR1 deficiency.

A series of Fe3O4-PES ultrafiltration membranes with different mass ratios of Fe3O4 and PAA were prepared from suspensions, using the phase inversion process. The suspensions consisted of polyether sulfone (PES), dimethyl formamide, polyacrylic acid (PAA), and ferrosoferric oxide (Fe3O4). The separation properties of ultrafiltration membranes with different Fe3O4/PAA mass ratio were investigated by a cross-flow experimental system. The Fe3O4/PAA mass ratio had little effect on the rejection of membranes to BSA. However, the pure water flux had a slight decline and then rised rapidly with the increase of Fe3O4/PAA mass ratio. An interesting phenomenon observed was that the Fe3O4 particles could diffuse into the nonsolvent bath during the formation of membrane, and the amount of Fe3O4 extracted into the nonsolvent bath nearly kept a constant mass ratio to PAA, even if the Fe3O4/PAA proportion was changed. The reasons of this interesting phenomenon were investigated. This result indicates that modified inorganic fillers may be used as the pore-forming agent to prepare the porous membranes like the template leaching method. At the same time, this method does not use any strong acid or base. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013

According to the physical principles of hydrostatics, we measure the gravitational acceleration by using the air specific heat ratio comprehensive instrument and an inverted test tube with a pressure sensor at the bottom of it. The experiment is simple and does not involve the measurement of time. The result is good.

During viral infection, extracellular dsRNA is a potent signaling molecule that activates many innate immune cells, including macrophages. TLR3 is a well-known receptor for extracellular dsRNA, and internalization of extracellular dsRNA is required for endosomal TLR3 activation. Preserved inflammatory responses of TLR3-deficient macrophages to extracellular dsRNA strongly support a TLR3-independent mechanism in dsRNA-mediated immune responses. The present study demonstrated that CD11b/CD18 (Mac-1 [macrophage-1 Ag]), a surface integrin receptor, recognized extracellular dsRNA and induced macrophage immune responses. CD11b deficiency reduced inflammatory cytokine induction elicited by polyinosinic:polycytidylic acid (poly I:C; a synthetic dsRNA) in mouse sera and livers, as well as in cultured peritoneal macrophages. dsRNA-binding assay and confocal immunofluorescence showed that Mac-1, especially the CD11b subunit, interacted and colocalized with poly I:C on the surface of macrophages. Further mechanistic studies revealed two distinct signaling events following dsRNA recognition by Mac-1. First, Mac-1 facilitated poly I:C internalization through the activation of PI3K signaling and enhanced TLR3-dependent activation of IRF3 in macrophages. Second, poly I:C induced activation of phagocyte NADPH oxidase in a TLR3-independent, but Mac-1–dependent, manner. Subsequently, phagocyte NADPH oxidase–derived intracellular reactive oxygen species activated MAPK and NF-κB pathways. Our results indicate that extracellular dsRNA activates Mac-1 to enhance TLR3-dependent signaling and to trigger TLR3-independent, but Mac-1–dependent, inflammatory oxidative signaling, identifying a novel mechanistic basis for macrophages to recognize extracellular dsRNA to regulate innate immune responses. This study identifies Mac-1 as a novel surface receptor for extracellular dsRNA and implicates it as a potential therapeutic target for virus-related inflammatory diseases.

// Jun-Hui Sun 1 , Guan-Hui Zhou 1 , Yue-Lin Zhang 1 , Chun-Hui Nie 1 , Tan-Yang Zhou 1 , Jing Ai 2 , Tong-Yin Zhu 1 , Wei-Lin Wang 1 , Shu-Sen Zheng 1 1 Division of Hepatobiliary and Pancreatic Interventional Center, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, P.R. China 2 Department of Ophthalmology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, P.R. China Correspondence to: Shu-Sen Zheng, email: shusenzheng@zju.edu.cn Keywords: chemoembolization, TACE, liver cancer, hepasphere microsphere, drug eluting microsphere Received: August 08, 2016 Accepted: December 07, 2016 Published: December 27, 2016 ABSTRACT Transcatheter arterial chemoembolization (TACE) is the mainstay of treatment for unresectable hepatocellular carcinoma (HCC). The efficacy of conventional TACE (cTACE) in liver metastases is not satisfactory, which might be due to the fact of embolic material used. Recently, as a new type of drug-loading microsphere, HepaSphere has been introduced in China. In this study, there were total 30 patients (18 males and 12 females) with liver cancer underwent embolization with Hepasphere microsphere. And a total of 44 TACE procedures were performed using 50-100μm HepaSphere. There were 16 patients diagnosed as HCC and 14 patients as liver metastases. The follow up period ranged from 3 to 15 months (median 10 months). Response rates were calculated on intention-to-treat basis. One month after TACE, total objective response was 63.3% and disease control rate was 86.7%. No severe complication (such as infection, liver abscess, abdominal bleeding, tumor rupture) was observed. In conclusion, chemoembolization with Hepasphere microsphere may be a safe and possibly effective palliative treatment for patients with liver cancer.

Misfolded α-synuclein (α-Syn) aggregates participate in the pathogenesis of synucleinopathies, such as Parkinson’s disease. Whereas much is known about how the various domains within full-length α-Syn (FL-α-Syn) contribute to the formation of α-Syn aggregates and therefore to their neurotoxicity, little is known about whether the individual peptides that can be generated from α-syn, possibly as intermediate metabolites during degradation of misfolded α-Syn aggregates, are neurotoxic themselves. A series of synthesized α-Syn peptides, corresponding to the locus in FL-α-Syn containing alanine 30, substitution of which with a proline causes a familial form of Parkinson’s disease, were examined for their capacity of inducing release of microglial superoxide. The neurotoxicity of these peptides was measured according to their influence on the ability of neuroglial cultures deficient in gp91 phox , the catalytic unit of NADPH oxidase (Nox2), or wild-type cultures to take up 3H-labeled dopamine and on the number of tyrosine hydroxylase-staining-positive neurons. Western blots and confocal images were utilized to analyze membrane translocation of p47 phox and p67 phox , phosphorylation of p47 phox and Erk1/2 kinase, and binding of α-Syn peptides to gp91 phox . Activation of brain microglia in mice injected with α-Syn peptides was demonstrated by immunostaining for major histocompatibility complex (MHC)-II along with qPCR for Iba-1 and MHC-II. We report α-Syn (29-40) as a specific peptide capable of activating microglial Nox2 to produce superoxide and cause dopaminergic neuronal damage. Administered to mice, this peptide also activated brain microglia to increase expression of MHC-II and Iba-1 and stimulated oxidation reaction. Exploring the underlying mechanisms showed that α-Syn (29-40) peptide triggered Nox2 to generate extracellular superoxide and its metabolite H2O2 by binding to the catalytic unit gp91 phox of Nox2; diffusing into cytosol, H2O2 activated Erk1/2 kinase to phosphorylate p47 phox and p67 phox and further activated Nox2, establishing a positive feedback loop to amplify the Nox2-mediated response. Collectively, our study suggests novel information regarding how α-Syn causes neuronal injury, possibly including mechanisms involving abnormal metabolites of α-Syn aggregates.

This paper presents an improvement cuckoo search (ICS) algorithm for minimizing the project duration of the resource-constrained project scheduling problem with generalized precedence relations (RCPSP/max). The ICS algorithm is designed as follows, each individual is coded based on the priority of activity for scheduling as to be in a form which is suitable for matching the characteristics of Levy flight, and the individual should be resolved by serial schedule generation scheme with the improved double justification. To avoid low efficiency and local minimum, an elite individual local search method is adopted in CS. Finally, computational results in the RCPSP/max benchmarks show the efficiency of the proposed algorithm.

SIRT2, a member of the sirtuin (SIRT1-7) family, is a tubulin deacetylase. It has been reported that SIRT2 mediates cellular stress responses and is highly expressed in vascular endothelial cells, while its roles in cell survival and energy metabolism of endothelial cells remain unknown. In the current study, we tested our hypothesis that SIRT2 plays an important role in the cell survival and energy metabolism of endothelial cells, using a porcine vascular endothelial cell line (PIEC) as a cellular model. Our study showed that both SIRT2 inhibitor AGK2 and SIRT2 siRNA led to a significant reduction of the cell survival of PIEC cells. Our FACS-based Annexin V/7-AAD assay and Hoechst staining showed that both SIRT2 inhibitor and SIRT2 siRNA led to a significant increase in apoptosis and necrosis of the cells. Moreover, the SIRT2 inhibition led to both mitochondrial depolarization and decreases in the intracellular ATP level of the cells. Collectively, our study has provided the first evidence suggesting that SIRT2 plays a significant role in maintaining both the survival and the mitochondrial membrane potential of PIEC cells, which may account for the major effects of SIRT2 on the intracellular ATP level of the cells.

Aim was to assess the therapeutic value of portal vein stenting (PVS) combined with iodine-125 seed (125I seed) strand endovascular implantation followed by transcatheter arterial chemoembolization (TACE) for treating patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). This was a retrospective study of 34 patients aged 29–81 years, diagnosed HCC with PVTT, and treated with PVS combined with125I seed strand endovascular implantation followed by TACE between January 2012 and August 2014. Survival, stent patency, technical success rate, complications related to the procedure, and adverse events were recorded. The technical success rate was 100%. No serious procedure-related adverse event was recorded. The median survival was 147 days. The cumulative survival rates and stent patency rates at 90, 180, and 360 days were 94.1%, 61.8%, and 32.4% and 97.1% (33/34), 76.9% (24/34), and 29.4% (10/34), respectively. PVS combined with125I seed strand endovascular implantation followed by TACE is feasible for patients with HCC and PVTT. It resulted in appropriate survival and stent patency, with no procedure-related adverse effects.

In this paper, the C-doped TiO2was prepared by hydrothermal method with butyl titanate and glucose as the precursors. Then, C-doped TiO2was further modified by CTAB during the above hydrothermal method. The synthesized samples were characterized by BET before and after the modification. The results show that the surface area of C-doped TiO2became smaller after the modification (from 236 m2/g to 99.7 m2/g), but the adsorption amount for methyl orange was enhanced greatly after the modification. The biggest adsorption amount for methyl orange was up to188.7 mg/g for modified TiO2-XCXin the methyl orange solution of 200 mg/L.

Emerging evidence has indicated microRNAs are involved in tumor development and progression, acting as tumor suppressors or oncogenes. Here we report that miR-409-3p was significantly downregulated in gastric cancer (GC) cell lines and tissues. Overexpression of miR-409-3p in SGC-7901 gastric cancer cells dramatically suppressed cell proliferation and induced cell apoptosis both in vitro and in vivo. Furthermore, we demonstrate that the transcriptional regulator PHF10 was a target of miR-409-3p. Taken together, these findings suggest that miR-409-3p may function as a novel tumor suppressor in GC and its anti-oncogenic activity may involve the direct targeting and inhibition of PHF10.

Accumulating evidence has shown that microRNAs are involved in multiple processes in cancer development and progression. Here, we report that expression of miR-625 is significantly down-regulated and negatively correlated with lymph node metastasis in gastric cancer. miR-625 significantly inhibits invasion and metastasis of gastric cancer cells both in vitro and in vivo. Moreover, we identify that ILK is a direct target gene for miR-625 and knockdown of ILK has a phenocopy of overexpression of miR-625. Taken together, our findings suggest that miR-625 plays an important role in the mechanism of tumor metastasis.

The transplantation of endothelial progenitor cells (EPCs) provides a novel method for the treatment of human tumors or vascular diseases. Magnetic resonance imaging (MRI) has proven to be effective in tracking transplanted stem cells by labeling the cells with superparamagnetic iron oxide (SPIO) nanoparticles. The SPIO has been used to label and track the EPCs; however, the effect of SPIO upon EPCs remains unclear on a cellular level. In the present study, EPCs were labeled with home-synthesized SPIO nanoparticles in vitro and the biological characteristics of the labeled EPCs were evaluated. The EPCs were isolated from the peripheral blood of New Zealand rabbits and cultured in fibronectin-coated culture flasks. The EPCs were labeled with home-synthesized SPIO nanoparticles at a final iron concentration of 20 μg/ml. Labeled EPCs were confirmed with transmission electron microscopy and Prussian blue staining. The quantity of iron/cell was detected by atomic absorption spectrometry. The membranous antigens of EPCs were detected by cytofluorimetric analysis. Cell viability and proliferative capability between the labeled and unlabeled EPCs were compared. The rabbit EPCs were effectively labeled and the labeling efficiency was approximately 95%. The SPIO nanoparticles were localized in the endosomal vesicles of the EPCs, which were confirmed by transmission electron microscopy. No significant differences were found in cell viability and proliferative capability between labeled and unlabeled EPCs (P>0.05). In conclusion, rabbit peripheral blood EPCs were effectively labeled by home-synthesized SPIO nanoparticles, without influencing their main biological characteristics.

CD38 is a multifunctional enzyme that can not only generate cyclic adenosine diphosphate-ribose (cADPR) - a key Ca(2+) -mobilizing second messenger - by consuming NAD(+), but also hydrolyze extracellular NAD(+). There have been only a small number of studies on the functions of CD38 in the CNS. Brain inflammation plays critical roles in ischemic brain injury and multiple other neurological diseases, in which microglia activation is a key event. In this study we determined the roles of CD38 in the basal survival of mouse BV2 microglia cells by applying CD38 siRNA. Our study found that silencing of CD38 led to significantly decreased survival of the cells. We also found that decreased CD38 levels can lead to apoptosis of the microglial cells, as assessed by flow cytometry-based Annexin V/7-AAD assay, caspase-3 immunostaining and Hoechst staining assays. Our study has further indicated that the CD38 silencing-induced apoptosis is mainly caspase 3-dependent. Collectively, our study has provided the first evidence suggesting that CD38 plays a critical role in the basal survival of microglia, and decreased CD38 can lead to caspase 3-dependent apoptosis of the cells. These results suggest that CD38 may become a therapeutic target for modulating microglial survival in neurological diseases.

Numerous studies have indicated that four interacting factors, including oxidative stress, mitochondrial alterations, calcium dyshomeostasis and inflammation, play crucial pathological roles in multiple major neurological diseases, including stroke, Alzheimer's disease (AD) and Parkinson's disease (PD). Increasing evidence has also indicated that NAD(+) plays important roles in not only mitochondrial functions and energy metabolism, but also calcium homeostasis and inflammation. The key NAD(+)-consuming enzyme--poly(ADP-ribose) polymerase-1 (PARP-1) and sirtuins--have also been shown to play important roles in cell death and aging, which are two key factors in the pathology of multiple major age-dependent neurological diseases: PARP-1 plays critical roles in both inflammation and oxidative stress-induced cell death; and sirtuins also mediate the process of aging, cell death and inflammation. Thus, it is conceivable that increasing evidence has suggested that NAD(+) metabolism and NAD(+)-dependent enzymes are promising targets for treating a number of neurological illnesses. For examples, the key NAD(+)-dependent enzymes SIRT1 and SIRT2 have been indicated to strongly affect the pathological changes of PD and AD; PARP-1 inhibition can profoundly reduce the brain injury in the animal models of multiple neurological diseases; and administration of either NAD(+) or nicotinamide can also decrease ischemic brain damage. Future studies are necessary to further investigate the roles of NAD+ metabolism and NAD⁺-dependent enzymes in neurological diseases, which may expose novel targets for treating the debilitating illnesses.

SIRT2 is a tubulin deacetylase, which can play either detrimental or beneficial roles in cell survival under different conditions. While it has been suggested that reduced SIRT2 expression in human gliomas may contribute to development of gliomas, there has been no study that directly determines the effects of decreased SIRT2 activity on the survival of glioma cells. In this study we applied both pharmacological and molecular approaches to determine the roles of SIRT2 in the survival of glioma cells. Our studies, by conducting such assays as flow cytometry-based Annexin V assay and caspase-3 immunostaining, have indicated that decreased SIRT2 activity leads to apoptosis of C6 glioma cells by caspase-3-dependent pathway. Our experiments have further shown that reduced SIRT2 activity produces necrosis of C6 glioma cells. Moreover, our study applying SIRT2 siRNA has also shown that decreased SIRT2 leads to both necrosis and apoptotic changes of C6 glioma cells. Collectively, our study has provided novel evidence indicating that SIRT2 activity plays a key role in maintaining the survival of glioma cells, and that reduced SIRT2 activity can induce both necrosis and caspase-3-dependent apoptosis of C6 glioma cells. These results have also suggested that inhibition of SIRT2 might become a novel therapeutic strategy for gliomas.

A nested Ecomsed model with high resolution grid has been developed and used to simulate typical typhoon storm surge (0608 typhoon) which landed on the coast of Zhejiang. Two main pressure modes have been considered in this model: Jelesnianski65 (J65) and Fujita &Takahashi (FJ) model. This study found that FJ model is agree better with the measured values than J65 model. The model has been used to simulate the water level which has been compared with the available field observations (Kanmen; Wenzhou; and Dachen stations). The results show that the error of the peak water level is about 50-70 cm in the first domain and the nested model improves the accuracy which is around 30–50cm(under 30 cm during ebb). The relative error is lower and the time effect is more accurate in the nested small domain. Thus, it is suggested that to simulate and predict typhoon storm surge a nested Ecomsed be adopted.

A simple and efficient detection algorithm is proposed for the problem of image jitter detection in video quality diagnosis system. In the algorithm the gray projection feature is selected to calculate the correlation of motion vector, which effectively solve the threshold selection problem. PCA is used to calculate the main direction of displacement vector. And the projection relationship of motion vectors in the main direction of displacement vector is used to judge the jitter. This way effectively utilizes the statistical characteristics, enhances the ability of anti-noise and reduces the rate of false positives. Experimental results show that the proposed algorithm can effectively detect the jitter of video images, and can meet the needs of the actual work.

The rabbit VX2 hepatic tumor model has been widely used for the investigation of liver cancer. The present study was designed to compare two inoculation methods in order to identify an improved modality for establishing rabbit hepatic tumors. A total of 44 rabbits were randomly divided into 2 groups. All inoculations were performed by open laparotomy. In group 1, 22 rabbits received a VX2 tumor cell suspension in a volume of 0.2 ml, which was slowly injected into the rabbit liver parenchyma using an 18-gauge needle. In group 2, a 0.2-ml suspension of small, minced tumor fragments of a VX2 carcinoma, inserted into an 18-gauge needle, was implanted into the liver parenchyma. The tumor survival ratio, size and extrahepatic metastases were evaluated and compared using computed tomography (CT)-scan, angiography and pathological specimens. At 2 weeks following implantation, successful liver tumor growth was achieved in 14 out of the 22 rabbits in group 1 (63.6%) and 21 out of the 22 rabbits in group 2 (95.5%) (P

A visible-light-driven photocatalyst Ag3PO4 was prepared by a novel precipitation- replacement process. The synthesized sample was cubic crystals with the bandgap of 2.16 eV. And most of the particles size was among 0.5~2 mm. The Ag3PO4 shows high photocatalytic activity for the degradation of methyl orange (MO) solution under the visible light (l>420 nm). The apparent ratio constant (kapp) value of Ag3PO4 was about 239 and 50 times that of P25 and C-TiO2, respectively.

A novel visible-light-active C-N-Cl-codoped TiO2 photocatalyst was prepared by a simple process. The as-prepared sample was characterized by XRD, XPS, and UV-Vis. The analysis results showed that the as-synthesized sample was anatase and possessed a narrow bad gap of 2.4 eV after the doping of carbon, nitrogen and chlorine. An obvious absorption for visible light was observed in the range of 400~700 nm for C-N-Cl-codoped TiO2. By degrading of methyl orange (MO) solution under the visible light (l>420 nm) irradiation, the synthesized photocatalyst showed 5 times photocatalytic activity than that of P25.

A new visible-light-driven plasmonic photocatalyst Ag/AgCl/TiO2-XCX was prepared by a two-step synthesis process. The bandgap of the synthesized sample was 2.87 eV. In the degradation of methyl orange (MO) solution under the visible light (l>420 nm), the Ag/AgCl/TiO2-X CX shows higher photocatalytic activity than TiO2-X C X . The apparent ratio constant (kapp) value of Ag/AgCl/TiO2-XCX was about 9.7 times that TiO2-XCX.

A magnetically separable photocatalyst silver vanadates@SiO2/Fe3O4 was prepared by hydrothermal process. The prepared sample was composed of mixed phases of a–Ag3VO4 and Ag4V2O4, and the main phase was a–Ag3VO4. The bandgap of the synthesized sample was 2.2 eV. In the degradation of methyl orange (MO) solution under the visible light (l>420 nm), the silver vanadates@SiO2/Fe3O4 showed high photocatalytic activity in two-cycle photocatalytic test.

Hepatitis B virus (HBV) precore G1896A mutation is associated with Hepatitis B e antigen (HBeAg) seroconversion. This mutation and the adjacent G1899A mutation also appear to associate with increased risk of hepatocellular carcinoma. Quantitative mutant dynamics may help determine the potential of these mutants as clinical biomarkers. However, a reliable method to quantify either mutant is not available, partly because the viral genome has polymorphisms in general and the precore mutations are complex.(1) To develop a reliable and ultrasensitive assay for the quantification of HBV G1896A and/or G1899A mutants. (2) To obtain preliminary data on the quantities of the precore mutants in patients.A SimpleProbe real time PCR assay was developed to quantify the HBV precore mutants. Dual melting analysis and a primer-probe partial overlap approach were used to increase detection accuracy. A wild-type selective PCR blocker was also developed to increase mutant detection sensitivity.The assay correctly identified the precore sequence from all 62 patient samples analyzed. More than 97% of precore sequences in the GenBank can be recognized. Mutant detection sensitivity reached 0.001% using a wild type-selective PCR blocker. At least one precore mutant can be detected from all 20 HBeAg-positive individuals who were negative for precore mutations by DNA sequencing.The reliability of this ultrasensitive mutation quantification assay was demonstrated. The same approaches may be useful for the detection of other clinically significant mutations. Evolution of the precore mutants warrants further studies.

Hepatitis B virus (HBV) carrying the A1762T/G1764A double mutation in the basal core promoter (BCP) region is associated with HBe antigen seroconversion and increased risk of liver cirrhosis and hepatocellular carcinoma (HCC). Quantification of the mutant viruses may help in predicting the risk of HCC. However, the viral genome tends to have nucleotide polymorphism, which makes it difficult to design hybridization-based assays including real-time PCR. Ultrasensitive quantification of the mutant viruses at the early developmental stage is even more challenging, as the mutant is masked by excessive amounts of the wild-type (WT) viruses. In this study, we developed a selective inhibitory PCR (siPCR) using a locked nucleic acid-based PCR blocker to selectively inhibit the amplification of the WT viral DNA but not the mutant DNA. At the end of siPCR, the proportion of the mutant could be increased by about 10,000-fold, making the mutant more readily detectable by downstream applications such as real-time PCR and DNA sequencing. We also describe a primer-probe partial overlap approach which significantly simplified the melting curve patterns and minimized the influence of viral genome polymorphism on assay accuracy. Analysis of 62 patient samples showed a complete match of the melting curve patterns with the sequencing results. More than 97% of HBV BCP sequences in the GenBank database can be correctly identified by the melting curve analysis. The combination of siPCR and the SimpleProbe real-time PCR enabled mutant quantification in the presence of a 100,000-fold excess of the WT DNA.

This paper briefly introduces the composition of central heating data transmission system which bases on 3G wireless networks and the realization of communication. The dates of temperature, flow and pressure, etc, are collected in remote heat-exchange station and are transmitted to dispatch center through 3G wireless network. Due to this, the remote monitoring for the whole heating system is implemented in the dispatch center, which solves the problems of being difficult to collect thermal parameters for the whole system and the unevenness of heat distribution. The result of operation indicates that the system is stable, and offers high regulation accuracy and is easily operated, which meets the requirements of long-term stable operation of remote monitoring.

A visible-light-active C-doped TiO2 photocatalyst was prepared by a simple wet process. The XPS analysis results showed that carbon was doped into TiO2 particles and one kind of carbonate species with Ti-O-C structure was formed. The obtained sample showed obvious absorption in the 400-800 nm range in UV-vis spectra. By degrading of methyl orange (MO) solution under visible light irradiation (l>420 nm), the apparent rate constant (kapp) of S170 was about 10 times larger than that of P25. The preparation procedure of such C-doped catalyst can be easily scaled up for industrial production due to its simplicity.

The heteropoly acid catalyst of H5PMo10V2O40 supported on SBA-15 mesoporous mole-cular sieve was prepared by an impregnation method and characterized by nitrogen physisorption, FT-IR,SEM, and used in catalytic synthesis of tributyl citrate. The results show that the heteropoly acid catalyst has fine dispersion characteristics, structural stability, high catalytic activity and better reusability.

Summary In many clinical studies with a survival outcome, administrative censoring occurs when follow-up ends at a prespecified date and many subjects are still alive. An additional complication in some trials is that there is noncompliance with the assigned treatment. For this setting, we study the estimation of the causal effect of treatment on survival probability up to a given time point among those subjects who would comply with the assignment to both treatment and control. We first discuss the standard instrumental variable (IV) method for survival outcomes and parametric maximum likelihood methods, and then develop an efficient plug-in nonparametric empirical maximum likelihood estimation (PNEMLE) approach. The PNEMLE method does not make any assumptions on outcome distributions, and makes use of the mixture structure in the data to gain efficiency over the standard IV method. Theoretical results of the PNEMLE are derived and the method is illustrated by an analysis of data from a breast cancer screening trial. From our limited mortality analysis with administrative censoring times 10 years into the follow-up, we find a significant benefit of screening is present after 4 years (at the 5% level) and this persists at 10 years follow-up.

In this letter, vertical GaN transistors fabricated on bulk GaN substrates are discussed. A threshold voltage of 0.5 V and saturation current >2.3 A are demonstrated. The measured devices show breakdown voltages of 1.5 kV and specific ON-resistance of 2.2 mΩ-cm 2 , which translates to a figure-of-merit of V BR 2 /R ON ~1 × 10 9 V 2 Ω -1 · cm -2 .

There is a great interest in monolithic GaN semiconductor devices with high current capability for power electronics. In this letter, large area vertical GaN p-n diodes fabricated on bulk GaN substrates are discussed. Diodes with areas as large as 16 ${\rm mm}^{2}$ with breakdown voltages exceeding 700 V and pulsed (100 $\mu{\rm s}$ ) currents approaching 400 A are reported. This is made possible for the first time in part due to the recent availability of improved quality bulk GaN substrates.

There is a great interest in wide band-gap semiconductor devices for power electronics application. In this letter, vertical GaN p-n diodes fabricated on bulk GaN substrates are discussed. The device layers are grown by MOCVD on low defect density (104 cm-2) bulk GaN substrates. The measured devices show breakdown voltages of 3.7 kV with an area differential specific on-resistance (Rsp) of 2.95 mΩ-cm2.

Previous transgenic-reporter and targeted-deletion studies indicate that the subset-specific expression of CD8αβ heterodimers is controlled by multiple enhancer activities, since no silencer elements had been found within the locus. We have identified such a silencer as L2a, a previously characterized ∼220 bp nuclear matrix associating region (MAR) located ∼4.5 kb upstream of CD8α. L2a transgenes driven by the E8 I enhancer showed no reporter expression in thymic subsets or T cells in splenic, inguinal and mesenteric lymph node peripheral T cells. Deletion of L2a resulted in significant reporter de-repression, even in the CD4 + CD8 + double positive (DP) thymocyte population. L2a contains binding sites for two MAR-interacting proteins, SATB1 and CDP. We found that that binding of these factors was markedly influenced by the content and spacing of L2a sub-motifs (L and S) and that SATB1 binds preferentially to the L motif both in vitro and in vivo. A small fraction of the transgenic CD8 single positive (SP) thymocytes and peripheral CD8 + T cells bypassed L2a-silencing to give rise to variegated expression of the transgenic reporter. Crossing the L2a-containing transgene onto a SATB1 knockdown background enhanced variegated expression, suggesting that SATB1 is critical in overcoming L2a-silenced transcription.

Chronic infection by hepatitis B virus (HBV) can result in cirrhosis, hepatic failure, and hepatocellular carcinoma (HCC) if left untreated. The extent of liver injury and the risk of HCC closely correlate with active viral replication, as indicated by high levels of circulating HBV DNA. Five oral antiviral agents, each targeting the viral DNA polymerase, are currently available in the United States to inhibit viral replication. Their effective use requires proper monitoring of drug resistance development. The current clinical guidelines recommend measuring “total” circulating HBV DNA to evaluate the efficacy of treatment and to serve as an indirect measure of drug-resistant mutant viruses. This may result in delayed identification of drug-resistant mutants that can cause hepatic injuries and decompensation. This review discusses the virologic mechanisms of drug resistance, the need and strategies for early detection of mutant viruses, and the recent studies on the prevention of drug resistance.

Bidirectional interactions between neurons and glial cells are crucial to the genesis of pathological pain. The mechanisms regulating these interactions and the role of this process in relaying synaptic input in the spinal dorsal horn remain to be established. We studied the role of glutamate transporters in the regulation of such interactions. On pharmacological blockade of glutamate transporters, slow inward currents (SICs) appeared spontaneously and/or were evoked by peripheral synaptic input in the spinal superficial dorsal horn neurons, including the spinothalamic tract neurons. We showed that the SICs were induced by the release of glutamate from glial cells. On inhibition of glutamate uptake, the stimulation-induced, synaptically released glutamate activated glial cells and caused glial cells to release glutamate. Glial-derived glutamate acted on extrasynaptic N-methyl-d-aspartate (NMDA) receptors mainly composed of NR2B receptors and generated SICs, which led to depolarization and action potential generation in superficial spinal dorsal horn neurons. Thus glutamate transporters regulate glutamatergic neuron–glia interactions at spinal sensory synapses. When glutamate uptake is impaired, glial cells function like excitatory interneurons—they are activated by peripheral synaptic input and release glutamate to activate postsynaptic neurons in spinal pain pathways.