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Abstract: The human ether-a-go-go-related gene (hERG) encodes the rapidly activating, delayed rectifier potassium channel (IKr) important for cardiac repolarization. Dysfunction of the hERG channel can cause Long QT Syndrome (LQTS). A wide variety of structurally diverse therapeutic compounds reduce the hERG current by acute direct inhibition of the hERG current or/and selective disruption of hERG protein expression. Arsenic trioxide (As2O3), which is used to treat acute promyelocytic leukemia, can cause LQTS type 2 (LQT2) by reducing the hERG current through the diversion of hERG trafficking to the cytoplasmic membrane. This cardiotoxicity limits its clinical applications. Our aim was to develop cardioprotective agents to decrease As2O3-induced cardiotoxicity. We reported that superfusion of hERG-expressing HEK293 (hERG-HEK) cells with matrine (1, 10μM) increased the hERG current by promoting hERG channel activation. Long-term treatment with 1μM matrine or oxymatrine increased expression of the hERG protein and rescued the hERG surface expression disrupted by As2O3. In addition, Matrine and oxymatrine significantly shortened action potential duration prolonged by As2O3 in guinea pig ventricular myocytes. These results were ascribed to the up-regulation of hERG at both mRNA and protein levels via an increase in the expression of transcription factor Sp1, an established transactivator of the hERG gene. Therefore, matrine and oxymatrine may have the potential to cure LQT2 as a potassium channel activator by promoting hERG channel activation and increasing hERG channel expression. [Copyright &y& Elsevier]

In this paper, we propose a novel method called dynamic transition embedding (DTE) for linear dimensionality reduction. Differing from the recently proposed manifold learning-based methods, DTE introduces the dynamic transition information into the objective function by characterizing the Markov transition processes of the data set in time t( t > 0). In the DTE framework, running the Markov chain forward in time, or equivalently, taking the larger powers of Markov transition matrices integrates the local geometry and, therefore, reveals relevant geometric structures of the data set at different timescales. Since the Markov transition matrices defined by the connectivity on a graph contain the intrinsic geometry information of the data points, the elements of the Markov transition matrices can be viewed as the probabilities or the similarities between two points. Thus, minimizing the errors of the probability reconstruction or similarity reconstruction instead of the least-square reconstruction in the well-known manifold learning algorithms will obtain the optimal linear projections with respect to preserving the intrinsic Markov processes of the data set. Comprehensive comparisons and extensive experiments show that DTE achieves higher recognition rates than some well-known linear dimensionality reduction techniques. [ABSTRACT FROM AUTHOR]

Abstract: Microbe-assisted phytoremediation is emerging as one of the most effective means by which plants and their associated rhizosphere microbes degrade organic contaminants in soils. A pot study was conducted to examine the effects of inoculation with Rhizobium meliloti on phytoremediation by alfalfa grown for 90 days in an agricultural soil contaminated with weathered polycyclic aromatic hydrocarbons (PAHs). Planting with uninoculated alfalfa (P) and alfalfa inoculated with R. meliloti (PR) significantly lowered the initial soil PAH concentrations by 37.2 and 51.4% respectively compared with unplanted control soil. Inoculation with R. meliloti significantly increased the counts of culturable PAH-degrading bacteria, soil microbial activity and the carbon utilization ability of the soil microbial community. The results suggest that the symbiotic association between alfalfa and Rhizobium can stimulate the rhizosphere microflora to degrade PAHs and its application may be a promising bioremediation strategy for aged PAH-contaminated soils. [Copyright &y& Elsevier]

Abstract: Poly(pyrrole-co-aniline) (PPyA) copolymer nanofibers were prepared by chemical oxidation method with cetyltrimethyl ammonium chloride (CTAC) as template, and the nano-sulfur/poly(pyrrole-co-aniline) (S/PPyA) composite material in lithium batteries was achieved via co-heating the mixture of PPyA and sublimed sulfur at 160°C for 24h. The component and structure of the materials were characterized by FTIR, Raman, XRD, and SEM. PPyA with nanofiber network structure was employed as a conductive matrix, adsorbing agent and firm reaction chamber for the sulfur cathode materials. The nano-dispersed composite exhibited a specific capacity up to 1285mAhg−1 in the initial cycle and remained 866mAhg−1 after 40 cycles. [Copyright &y& Elsevier]

Homopolyimides are prepared by 4,4′-(ethyne-1,2-diyl)diphthalic anhydride as dianhydride monomer and several diamine monomers. The copolyimides are prepared with 4,4′-oxydianiline as an amine monomer， 3,3′,4,4′-oxydiphthalic anhydride as an anhydride monomer with the addition of 4,4′-(ethyne-1,2-diyl)diphthalic anhydride as another anhydride monomer. The structure of polyimides is characterized by Fourier transform infrared spectroscopy and X-ray diffraction. Thermogravimetric analysis, thermomechanical analysis and thermo-oxidative degradation kinetics analysis are used to investigate the properties of polyimides. The homopolyimide show the best thermal stability in both nitrogen and air atmosphere by 4,4′-oxydianiline and 4,4′-(ethyne-1,2-diyl)diphthalic anhydride. The results also indicate that the thermally cross-linkable copolyimide films not only enhance the thermal stability behaviors of polyimide by controlling the addition of dianhydride, but also improve substantially the upper limit temperature of thermal aging by undergoing chemical cross-linking reaction of the diphenylethynylene structures and providing multifarious naphthalene ring groups and biphenyl structures. Diphenylacetylene crosslinking merging to the long-chain of polyimide is a useful conversion for enhancing the thermal stability and the thermal degradation stability of aromatic polymers. [Display omitted] • Multi polyimides containing the diphenylethynylene structures were researched. • Studying on thermal aging and thermal properties of diphenylethynylene copolyimide. • Heat treatment can greatly improve the thermal properties of as-prepared polyimide. • Excellent thermal property (The upper limit aging temperature > 360 °C; T g > 300 °C). [ABSTRACT FROM AUTHOR]

Ovarian cancer is one of the leading causes of mortality in women worldwide. Currently, paclitaxel is one of the most effective chemotherapies. However, resistance to paclitaxel is a major cause of therapy failure and the precise mechanism of paclitaxel resistance remains unclear. In this study, we demonstrated that the oxidative pentose phosphate pathway (PPP) enzyme glucose-6-phosphate dehydrogenase (G6PD) promotes paclitaxel resistance. We showed that G6PD expression was higher in paclitaxel-resistant cancer cells than in their paclitaxel-sensitive counterparts. Furthermore, we demonstrated that suppressing G6PD using shRNA, or an inhibitor, either as single agents or in combination, sensitized paclitaxel-resistant cancer cells to paclitaxel treatment and thereby improving the therapeutic efficacy of paclitaxel. Interestingly, we found that the upregulation of G6PD in paclitaxel-resistant cells was due to the decreased expression of protein arginine methyltransferase 6 (PRMT6), which targets the promoter of G6PD. We further identified that G6PD promotes paclitaxel resistance by regulating the expression of glutathione S-transferase P1 (GSTP1), which confers resistance to chemotherapy by detoxifying several anticancer drugs. Taken together, our results suggest that G6PD is a novel potential target to overcome paclitaxel resistance. [ABSTRACT FROM AUTHOR]

The aggregation of two-dimensional (2D) layered nanofillers restricts their use as reinforcements in polymers. Herein, the bisphenol E cyanate ester resin (CE) nanocomposites based on surface functionalization of molybdenum disulfide (MoS 2) nanosheets with polysulfone (PSF) are prepared. In the structures, PSF segment were sandwiched between adjacent MoS 2 nanoplatelets, which restrained the restacking of the MoS 2 nanoplatelets. The compatibility between PSF modified MoS 2 and CE is improved as compared with MoS 2 and CE. The tensile strength and apparent shear strength of the nanocomposite show that modified MoS 2 nanosheets are very effective at increasing the adhesive and mechanical properties of cyanate esters at very low quality fractions. Pulling out effects, crack bridging, crack deflection, and crack pinning are the main strengthening mechanisms of mechanical properties. The glass transition temperature increases from 245 °C for the unfilled cyanate ester to 265 °C at 0.15 % MoS 2 loading. The results are consistent with the nanoconfinement effect including a nanoscale interfacial layer that can support the effective reinforcements of functionalized MoS 2 nanoplatelets over pure MoS 2. The excellent properties of MoS 2 /PSF/CE nanocomposites indicate that the approach in this study is effective to prepare high-performance molybdenum disulfide/cyanate ester polymer composites. [ABSTRACT FROM AUTHOR]

The aim of our study was to elucidate the landscapes of genetic alterations of TSC1 and TSC2 as well as other possible non-TSC1/2 in Lymphangioleiomyomatosis (LAM) patients. Sixty-one Chinese LAM patients' clinical information was collected. Tumor biopsies and matched leukocytes from these patients were retrospectively analyzed by next generation sequencing (NGS), chromosomal microarray analysis (CMA), and multiplex ligation-dependent probe amplification (MLPA). Eighty-six TSC1/2 variants were identified in 46 of the 61 LAM patients (75.4%) in which TSC2 and TSC1 variants were 88.37% and 11.63% respectively. The 86 variants are composed of (i) 52 single nucleotide variants (SNVs) (including 30 novel variants), (ii) 23 indels (including 21deletions, and 2 insertions), (iii) a germline duplication of exon 31–42 of TSC2, (iv) a 2.68 Mb somatic duplication containing TSC2, and (v) 9 regions with copy-neutral loss of heterogeneity (CN-LOHs) present only in the LAM patients with single TSC1/2 mutations. Sixty-one non-TSC1/2 variants in 31 genes were identified in 37 LAM patients. Combined applications of different techniques are necessary to achieve maximal detection rate of TSC1/2 variants in LAM patients. Thirty novel TSC1/2 variants expands the spectrum of TSC1/2 in LAM patients. Identification of 61 non-TSC1/2 variants suggests that alternative genes might have contributed to the initiation and progression of LAM. [ABSTRACT FROM AUTHOR]

Simple Summary: Avian coccidiosis, an infectious disease caused by seven species of Eimeria that can infect a bird's digestive tract and significantly retard its growth, is a serious economic disease for chickens. Many studies have demonstrated that host resistance to coccidiosis related to genetic variations can be improved by selective breeding. The parameters for evaluation of resistance to coccidiosis could be objective indicators, such as body weight gain and cecal lesion score, or biochemical indices, such as immune factors or cytokines in the plasma or serum. The aim of the study is to establish an optimal comprehensive evaluation model including a resistance index that can be detected in live chickens (slaughter traits cannot be selected in breeding) based on principal component analysis. The value of individual chickens calculated with the optimal evaluation model is associated with the cecum lesion score; the larger the value, the stronger the resistance to coccidiosis. This illustrated that the optimal model is effective in coccidiosis resistance selection. To establish a coccidiosis resistance evaluation model for chicken selection, the different parameters were compared between infected and control Jinghai yellow chickens. Validation parameters were selected for principal component analysis (PCA), and an optimal comprehensive evaluation model was selected based on the significance of a correlation coefficient between coccidiosis resistance parameters and principal component functions. The following six different parameters were identified: body weight gain 3–5 days post infection and catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA) and γ-interferon (IFN-γ) concentrations on the eight day post inoculation. Six principal components and one accumulated contribution of up to 80% of the evaluation models were established by PCA. The results showed that the first model was significantly or highly significantly related to nine resistance parameters (p < 0.01 or p < 0.05), especially to cecal lesions (p < 0.01). The remaining models were related to only 2–3 parameters (p < 0.01 or p < 0.05) and not to cecal lesions (p > 0.05). The values calculated by the optimal model (first model) were significantly negatively correlated with cecal lesion performance; the larger the value, the more resistant to coccidiosis. The model fi1 = −0.636 zxi1 + 0.311 zxi2 + 0.801 zxi3 − 0.046 zxi4 − 0.076 zxi5 + 0.588 zxi6 might be the best comprehensive selection index model for chicken coccidiosis resistance selection. [ABSTRACT FROM AUTHOR]

RNA binding motif 20 (RBM20) is a key regulator of pre-mRNA splicing of titin and other genes that are associated with cardiac diseases. Hormones, like insulin, triiodothyronine (T3), and angiotensin II (Ang II), can regulate gene-splicing through RBM20, but the detailed mechanism remains unclear. This study was aimed at investigating the signaling mechanism by which hormones regulate pre-mRNA splicing through RBM20. We first examined the role of RBM20 in Z-, I-, and M-band titin splicing at different ages in wild type (WT) and RBM20 knockout (KO) rats using RT-PCR; we found that RBM20 is the predominant regulator of I-band titin splicing at all ages. Then we treated rats with propylthiouracil (PTU), T3, streptozotocin (STZ), and Ang II and evaluated the impact of these hormones on the splicing of titin, LIM domain binding 3 (Ldb3), calcium/calmodulin-dependent protein kinase II gamma (Camk2g), and triadin (Trdn). We determined the activation of mitogen-activated protein kinase (MAPK) signaling in primary cardiomyocytes treated with insulin, T3, and Ang II using western blotting; MAPK signaling was activated and RBM20 expression increased after treatment. Two downstream transcriptional factors c-jun and ETS Transcription Factor (ELK1) can bind the promoter of RBM20. A dual-luciferase activity assay revealed that Ang II, but not insulin and T3, can trigger ELK1 and thus promote transcription of RBM20. This study revealed that Ang II can trigger ELK1 through activation of MAPK signaling by enhancing RBM20 expression which regulates pre-mRNA splicing. Our study provides a potential therapeutic target for the treatment of cardiac diseases in RBM20-mediated pre-mRNA splicing. [ABSTRACT FROM AUTHOR]

Long intergenic non-coding RNA No.668 (LINC00668) is implicated in the development of various malignancies. However, the role of LINC00668 and underlying mechanism in colorectal cancer (CRC) remains totally unknown. The expression pattern of LINC00668 in CRC cells were determined by qRT-PCR. CCK-8, EdU incorporation, flow cytometry, Transwell, and wound-healing assays were run to evaluate the functions of LINC00668 in CRC cells. Bioinformatics analyses were used to identify the LINC00668-specific binding with miRNAs that were screened by RNA pull-down. RNA immunoprecipitation and luciferase gene report assay were performed to confirm the interaction between miR-188–5p and LINC00668 in CRC cells. LINC00668 was significantly upregulated in CRC tissues and cells. Knockdown of LINC00668 suppressed cell proliferation and migration potential and induced cell apoptosis, but inhibition of miR-188–5p which was predicted to bind with LINC00668 reversed these effects. Furthermore, USP47 was a direct target of miR-188–5p, and overexpression of USP47 attenuated LINC00668 knockdown-induced tumor suppressive effects in CRC cells. Conclusively, our findings demonstrated that lncRNA LINC00668 acted as an oncogenic role in CRC cells by sponging miR-188–5p and upregulating USP47 and may represent a potential marker for CRC patients. [ABSTRACT FROM AUTHOR]

Background: Immunoglobulin A (IgA) and IgG are major components in human intestinal mucosal surface and sera, and IgA- or IgG-coated bacteria play a vital role in the intestinal homeostasis. However, the correlation of IgA, IgG and their coated bacteria with the clinical characteristics of inflammatory bowel disease (IBD) has not been fully clarified.Methods: The levels of soluble IgA and IgG in sera and feces were detected by ELISA, and the percentage of IgA- and IgG-coated bacteria in feces was analyzed by flow cytometry. Crohn's disease activity index (CDAI) and Simple Endoscopic Score for Crohn's disease (SES-CD) for Crohn's disease (CD) or Mayo score and ulcerative colitis endoscopic index of severity (UCEIS) for ulcerative colitis (UC), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were used to evaluate the disease activity.Results: 178 patients with CD, 75 patients with UC and 41 healthy donors were recruited in this study. We found that the concentrations of soluble IgA and IgG in feces of active IBD patients were significantly higher than those in healthy controls and that the levels of soluble IgA and IgG in feces from IBD patients were positively correlated with CRP, ESR, Mayo score, UCEIS, SES-CD, and CDAI, respectively. Moreover, we also observed that the percentage of IgA- and IgG-coated bacteria markedly increased in feces of IBD patients, especially in CD patients at the age of 17 to 40 years old, with terminal ileal lesions and perianal lesions, as well as from E2 UC patients, and was closely associated with disease activities.Conclusions: The levels of soluble IgA and IgG and the percentage of IgA- and IgG-coated bacteria strikingly increase in feces of IBD patients and correlate with disease activity. [ABSTRACT FROM AUTHOR]

Background: The tumour microenvironment conferred by mesenchymal stem cells (MSCs) plays a key role in tumour development and progression. We previously determined that platelet-activating factor receptor (PAFR) was overexpressed in ovarian cancer cells (OCCs) and that PAF can promote ovarian cancer progression via PAF/PAFR-mediated inflammatory signalling pathways. Evidence suggests that MSCs can secrete high concentrations of PAF. Here, we investigated the role of PAF/PAFR signalling in the microenvironment mediated by MSCs and OCCs and its effect on cancer progression.Methods: The PAF concentrations in the culture media of MSCs, OCCs and co-cultured MSCs and OCCs were determined by ELISA. The effects of MSCs on OCCs in vitro were assessed on cells treated with conditioned medium (CM). The expression and phosphorylation of key proteins in the PAF/PAFR signalling pathway were evaluated. In vivo, MSCs/RFP and SKOV3 cells were co-administered at different proportions to nude mice by interscapular injection. Mice in the WEB2086 group were intraperitoneally injected with the PAFR antagonist WEB2086 at a dose of 1 mg/kg.d for the duration of the animal experiments. Tumour progression was observed, and the weight and survival time of mice were measured. The PAF concentration in peripheral and tumour site blood was determined by ELISA.Results: High concentrations of PAF were detected in CM from MSCs and MSCs co-cultured with OCCs. Both types of medium promoted non-mucinous OCC proliferation and migration but had no effect on mucinous-type OCCs. These effects could be blocked by PAFR inhibitors. The expression and phosphorylation of key proteins in the PAF/PAFR pathway significantly increased upon treatment with PAF and MSC-CM. In vivo, the tumour volume was larger following co-injection of SKOV3 cells and MSCs/RFP than following injection of SKOV3 cells alone. The tumour-promoting effect of MSCs/RFP was blocked by the PAFR antagonist WEB2086. Serum PAF concentrations significantly increased in co-injected mice.Conclusion: Our results suggest that the tumour-promoting effect of MSCs on OCCs via their cross-talk in the tumour microenvironment was, at least in part, mediated by the PAF/PAFR pathway, suggesting a new target for the treatment of ovarian cancer. [ABSTRACT FROM AUTHOR]