Ag nanoparticles/PPV composite nanofibers with high and sensitive opto-electronic response

The novel Ag nanoparticles/poly(p-phenylene vinylene) [PPV] composite nanofibers were prepared by electrospinning. The transmission electron microscope image shows that the average diameter of composite fibers is about 500 nm and Ag nanoparticles are uniformly dispersed in the PPV matrix with an average diameter of about 25 nm. The Fourier transform infrared spectra suggest that there could be a coordination effect to a certain extent between the Ag atom and the π system of PPV, which is significantly favorable for the dissociation of photoexcitons and the charge transfer at the interface between the Ag nanoparticle and the PPV. The Au top electrode device of the single Ag/PPV composite nanofiber exhibits high and sensitive opto-electronic responses. Under light illumination of 5.76 mW/cm2 and voltage of 20 V, the photocurrent is over three times larger than the dark current under same voltage, which indicates that this kind of composite fiber is an excellent opto-electronic nanomaterial

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Whitening Degree Evaluation Method to Test Estimate Accuracy of Speckle Covariance Matrix

In the background of sea clutter, the accuracy of adaptive target detection is heavily influenced by the estimated performance of speckle covariance matrix. Generally, Normalized Frobenius Norm (NFN) is used to test the estimated accuracy of different speckle covariance matrix estimators, in which the requirement of a known real covariance matrix is hardly realized in the radar system. Therefore, in this study, a whitening degree evaluation method is proposed wherein the decorrelation of speckle covariance matrix in whitening filter processing of the radar system is fully exploited. It considers the correlation degree among pulses in the whitening clutter vector as the criterion to evaluate the estimate error of the speckle covariance matrix. The proposed method shows consistent conclusions with NFN on simulated data and also avoids limitations of the latter method in real data processing

Protocol for generating mutant zebrafish using CRISPR-Cas9 followed by quantitative evaluation of vascular formation

Summary: The use of vascular-specific transgenic zebrafish provides advantages for identifying new mutations affecting angiogenesis and vascular development. Here, we present a protocol for establishing, screening, and phenotyping CRISPR-Cas9-based mutagenesis in fluorescently labeled transgenic zebrafish. We describe steps for designing single-guide RNA (sgRNA) oligos, synthesizing sgRNA and Cas9 mRNA, and microinjection and generation of mutant lines. We then detail procedures for visualizing dynamic vasculature and quantitatively evaluating vascular formation in transgenic zebrafish.For complete details on the use and execution of this protocol, please refer to Luo et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics

Expression profile analysis of microRNAs in prostate cancer by next-generation sequencing

Purpose: Prostate cancer (PCa) is the second leading cause of tumor mortality among males in western societies. In China, the diagnostic and fatality rate of PCa is increasing yearly. MicroRNAs (miRNAs) are small single stranded non-coding RNA molecules (~22 nucleotides) which impede protein production by directly interacting with 3’-untranslated regions of the target mRNAs. miRNAs are crucial regulators in malignant tumors. Recent profiling research suggests that miRNAs are aberrantly expressed in PCa, and these have been implicated in the regulation of apoptosis, cell cycle, epithelial to mesenchymal transition, PCa stem cells, and androgen receptor pathway.Methods: To find miRNAs differentially expressed in PCa and their relation to prognostic factors and therapeutic potentials, we studied 24 surgical specimens from men who underwent radical prostatectomy, through high-throughput Illumina sequencing and quantitative real-time PCR (qRT-PCR) methods. Moreover, a variety of biological information softwares and databases were applied to predict the target genes of miRNA, molecular functions, and signal pathways. We also discuss the functional significance of the differentially expressed miRNAs and the molecular pathways/targets regulated by these miRNAs.Results: Many miRNAs were differentially expressed (fold change 2, P&lt;0.05) by sequencing. This was confirmed by qRT-PCR in more clinical tissue samples. In the tumors, miRNAs (miR-125b-5p, miR-126-5p, miR-141, miR-151a-5p, miR-221-3p and miR-222-3p) were significantly upregulated with downregulation of miR-486-5p and miR-488. In addition, 13 novel miRNAs were identified from three prostate tissue libraries, with 12 of them assayed in 21 human normal tissues by qRT-PCR. Multiple databases indicated target genes for these differentially expressed miRNAs. Function annotation of target genes indicated that most of them tend to target genes involved in signal transduction and cell communication, especially cancer-related PI3K-Akt and p53 signaling pathway. Moreover, miR-141 and miR-488 post-transcriptionally regulated androgen receptor (AR) expression, and inhibited the growth and metastasis of prostate gland epithelial cells.Conclusion: The small RNA transcriptomes obtained in this study uncovers the differentially expressed miRNAs, and provides a better understanding of the expression and function of miRNAs in the development of PCa and reveals several miRNAs in PCa that may have biomarker and therapeutic potentials.-----------------------------------------Cite this article as:  Song C, Chen H, Ru G, Ding Q, Yang W. Expression profile analysis of microRNAs in prostate cancer by next-generation sequencing. Int J Cancer Ther Oncol 2015; 3(4):3405.[This abstract was presented at the BIT’s 8th Annual World Cancer Congress, which was held from May 15-17, 2015 in Beijing, China.]</p

Expression profile analysis of microRNAs in prostate cancer by next-generation sequencing

Purpose: Prostate cancer (PCa) is the second leading cause of tumor mortality among males in western societies. In China, the diagnostic and fatality rate of PCa is increasing yearly. MicroRNAs (miRNAs) are small single stranded non-coding RNA molecules (~22 nucleotides) which impede protein production by directly interacting with 3’-untranslated regions of the target mRNAs. miRNAs are crucial regulators in malignant tumors. Recent profiling research suggests that miRNAs are aberrantly expressed in PCa, and these have been implicated in the regulation of apoptosis, cell cycle, epithelial to mesenchymal transition, PCa stem cells, and androgen receptor pathway.Methods: To find miRNAs differentially expressed in PCa and their relation to prognostic factors and therapeutic potentials, we studied 24 surgical specimens from men who underwent radical prostatectomy, through high-throughput Illumina sequencing and quantitative real-time PCR (qRT-PCR) methods. Moreover, a variety of biological information softwares and databases were applied to predict the target genes of miRNA, molecular functions, and signal pathways. We also discuss the functional significance of the differentially expressed miRNAs and the molecular pathways/targets regulated by these miRNAs.Results: Many miRNAs were differentially expressed (fold change 2, P&lt;0.05) by sequencing. This was confirmed by qRT-PCR in more clinical tissue samples. In the tumors, miRNAs (miR-125b-5p, miR-126-5p, miR-141, miR-151a-5p, miR-221-3p and miR-222-3p) were significantly upregulated with downregulation of miR-486-5p and miR-488. In addition, 13 novel miRNAs were identified from three prostate tissue libraries, with 12 of them assayed in 21 human normal tissues by qRT-PCR. Multiple databases indicated target genes for these differentially expressed miRNAs. Function annotation of target genes indicated that most of them tend to target genes involved in signal transduction and cell communication, especially cancer-related PI3K-Akt and p53 signaling pathway. Moreover, miR-141 and miR-488 post-transcriptionally regulated androgen receptor (AR) expression, and inhibited the growth and metastasis of prostate gland epithelial cells.Conclusion: The small RNA transcriptomes obtained in this study uncovers the differentially expressed miRNAs, and provides a better understanding of the expression and function of miRNAs in the development of PCa and reveals several miRNAs in PCa that may have biomarker and therapeutic potentials.-----------------------------------------Cite this article as:  Song C, Chen H, Ru G, Ding Q, Yang W. Expression profile analysis of microRNAs in prostate cancer by next-generation sequencing. Int J Cancer Ther Oncol 2015; 3(4):3405.[This abstract was presented at the BIT’s 8th Annual World Cancer Congress, which was held from May 15-17, 2015 in Beijing, China.

Comprehensive analysis for the immune related biomarkers of platinum-based chemotherapy in ovarian cancer

Background: Ovarian cancer (OC) is one of the most lethal gynecological malignancies. This study aimed to identify biomarkers that were sensitive to platinum-based chemotherapeutic agents and can be used in immunotherapy and explore the importance of their mechanisms of action. Methods: RNA-seq profiles and clinicopathological data for OC samples were obtained from The Cancer Genome Atlas (TCGA) and cBioPortal platform, respectively. Platinum-sensitive and platinum-resistant OC samples in the TCGA cohort were selected based on the clinical information. RNA-seq data for 70 OC samples withSingle-sample gene set enrichment analysis (ssGSEA) and unsupervised clustering were used to classify OC patients from the TCGA cohort into clusters with different proportions of infiltrating immune cells. ESTIMATE analysis was used to assess the immune landscape among clusters. Differential expression, univariate Cox regression, and LASSO regression analyses were performed to construct prognostic model. Spearman correlation analysis was conducted to investigate the correlations among immune checkpoint inhibitors (ICIs) and risk score, half-maximal drug inhibitory concentration (IC50) and risk score. Results: Using ssGSEA and unsupervised clustering, OC samples were divided into two clusters with different immune cell infiltration. Then, 1715 differentially expressed immune-related genes (DEIRGs) were identified between two clusters, 984 differentially expressed platinum-sensitive related genes (DEPSRGs) between 149 platinum-sensitive and 63 platinum-resistant OC samples were identified, and 5384 differentially expressed genes (DEGs) between 380 OC and 194 normal samples were detected from the TCGA cohort. Six biomarkers (GMPPB, SRPK1, STC1, PRSS16, HPDL, and SPTSSB) were detected to establish a prognostic model. The OC patients in the TCGA cohort were classified into high- and low-risk groups. The receive operating characteristic (ROC) curve was plotted and demonstrated that the prognostic model performed well with the area under ROC curve (AUC) greater than 0.6. The expressions of 5 ICIs, including CD200, TNFRSF18, CD160, CD200R1, and CD274 (PD-L1), were significantly different between two risk groups, and the risk score was significant negative associated with CTLA4, TNFRSF4, TNFRSF18, and CD274. Moreover, there were significant differences in IC50 of 10 chemo drugs between two risk groups, patients in the high-risk group could be more resistant to po0tinib, dasatinib, and neratinib. Conclusion: In summary, this study constructed a novel prognostic model based on six prognostic biomarkers, including GMPPB, SRPK1, STC1, PRSS16, HPDL, and SPTSSB, which can be utilized for predicting the prognosis of OC patients. These biomarkers were the potential therapeutic targets

Combined DLL3-targeted bispecific antibody with PD-1 inhibition is efficient to suppress small cell lung cancer growth

Background Small cell lung cancer (SCLC) accounts for 15% of lung cancers, and the primary treatment of this malignancy is chemotherapy and radiotherapy. Delta-like 3 (DLL3) is an attractive target for SCLC immunotherapy since its expression is highly restricted to SCLC with a neglectable appearance on normal adult tissues. In the current study, we aimed to explore the efficacy of DLL3-targeted SCLC immunotherapy via the engagement of T cell.Methods As a proof of concept, we constructed DLL3-targeted bispecific antibody and chimeric antigen receptor (CAR)-modified T cells. In vitro and in vivo tumor-suppression activity of these treatments alone or in combination with a Program Death-1 (PD-1) inhibitory antibody was evaluated.Results In vitro studies showed that both DLL3 bispecific antibody and CAR-T efficiently killed DLL3-positive cancer cells, including the native SCLC cell lines H446, H196, H82, and the artificial A431 cells that were forcefully overexpressing DLL3. In vivo studies in xenograft mouse models demonstrated that both bispecific antibody and CAR-T suppressed the tumor growth, and combination therapy with PD-1 inhibitory antibody dramatically improved the efficacy of the DLL3 bispecific antibody, but not the CAR-T cells.Conclusions Our results demonstrated that DLL3-targeted bispecific antibody plus PD-1 inhibition was effective in controlling SCLC growth

L1CAM promotes vasculogenic mimicry formation by miR‐143‐3p‐induced expression of hexokinase 2 in glioma

In recent decades, antiangiogenic therapy, which blocks the supply of oxygen and nutrition to tumor cells, has become a promising clinical strategy for the treatment of patients with tumors. However, recent studies revealed that vasculogenic mimicry (VM), which is the process by which vascular morphological structures are formed by highly invasive tumor cells, has been considered a potential factor for the failure of antiangiogenic therapy in patients with tumors. Thus, inhibition of VM formation might be a potential target for improving the outcome of antiangiogenic strategies. However, the mechanism underlying VM formation is still incompletely elucidated. Herein, we report that L1CAM might be a critical regulator of VM formation in glioma, and might be associated with the resistance of glioma to antiangiogenic therapy. We found that the tumor‐invasion and tube‐formation capabilities of L1CAM‐overexpressing cells were significantly enhanced in vitro and in vivo. In addition, the results indicated that miR‐143‐3p, which might directly target the 3'UTR of the hexokinase 2 (HK2) gene to regulate its protein expression, was subsequently involved in L1CAM‐mediated VM formation by glioma cells. Further study revealed that the regulation of MMP2, MMP9, and VEGFA expression was involved in this process. Moreover, we identified that activation of the downstream PI3K/AKT signaling pathway of the L1CAM/HK2 cascade is critical for VM formation by glioma cells. Furthermore, we found that the combined treatment of anti‐L1CAM neutralizing monoclonal antibody and bevacizumab increases efficacy beyond that of bevacizumab alone, and suppresses glioma growth in vivo, indicating that the inhibition of L1CAM‐mediated VM formation might efficiently improve the effect of antiangiogenic treatment for glioma patients. Together, our findings demonstrated a critical role of L1CAM in regulating VM formation in glioma, and that L1CAM might be a potential target for ameliorating tumor resistance to antiangiogenic therapy in glioma patients

Nuclear translocation of cGAS orchestrates VEGF-A-mediated angiogenesis

Summary: Cyclic GMP-AMP synthase (cGAS) senses cytosolic incoming DNA and consequently activates stimulator of interferon response cGAMP interactor 1 (STING) to mount immune response. Here, we show nuclear cGAS could regulate VEGF-A-mediated angiogenesis in an immune-independent manner. We found VEGF-A stimulation induces cGAS nuclear translocation via importin-β pathway. Moreover, nuclear cGAS subsequently regulates miR-212-5p-ARPC3 cascade to modulate VEGF-A-mediated angiogenesis through affecting cytoskeletal dynamics and VEGFR2 trafficking from trans-Golgi network (TGN) to plasma membrane via a regulatory feedback loop. In contrast, cGAS deficiency remarkably impairs VEGF-A-mediated angiogenesis in vivo and in vitro. Furthermore, we found strong association between the expression of nuclear cGAS and VEGF-A, and the malignancy and prognosis in malignant glioma, suggesting that nuclear cGAS might play important roles in human pathology. Collectively, our findings illustrated the function of cGAS in angiogenesis other than immune surveillance, which might be a potential therapeutic target for pathological angiogenesis-related diseases