Pyrimidine-thioindole inhibits gastric cancer cell proliferation via up-regulation of expression of tumor suppressor miR-145

Purpose: To investigate the effect of pyrimidine-thioindole on gastric cancer proliferation and the underlying mechanism of action. Methods: Cell viability and apoptosis were determined using MTT assay and Annexin V/PI assay, respectively. Reverse transcription-polymerase chain reaction (RT-PCR) was used for the determination of expression levels of miR-145, while protein expression levels were assayed by western blotting. Results: Pyrimidine-thioindole treatment significantly inhibited the proliferation of AGS and SNU-5 cells (p < 0.05), but had no effect on the viability of GES-1 cells. Exposure to pyrimidine-thioindole at doses of 8 and 10 µM significantly enhanced the apoptosis of AGS and SNU-5 cells (p < 0.05). Pyrimidinethioindole exposure markedly increased the proportions of AGS and SNU-5 cells in G1 phase (p < 0.05). In AGS and SNU-5 cell lines, pyrimidine-thioindole exposure at doses of 8 and 10 µM significantly upregulated the expression of miR-145, with higher enhancement of miR-145 expression in AGS cells than in SNU-5 cells. Moreover, pyrimidine-thioindole downregulated the expressions of MMP-2, MMP-9, c-Myc, p-PI3K and p-AKT in AGS and SNU-5 cells. Pyrimidine-thioindole treatment enhanced the expression of p21 in AGS and SNU-5 cells, relative to untreated cells (p < 0.05). Conclusion: These results suggest that pyrimidine-thioindole activates apoptotic signaling pathway, leading to reduction in cell proliferation and arrest of cell cycle. Moreover, it de-activates PI3K/AKT pathway and promotes miR-145 expression in AGS and SNU-5 cells. Thus, pyrimidine-thioindole has therapeutic significance for the management of gastric cancer

A Cognitive Method for Automatically Retrieving Complex Information on a Large Scale

Modern retrieval systems tend to deteriorate because of their large output of useless and even misleading information, especially for complex search requests on a large scale. Complex information retrieval (IR) tasks requiring multi-hop reasoning need to fuse multiple scattered text across two or more documents. However, there are two challenges for multi-hop retrieval. To be specific, the first challenge is that since some important supporting facts have little lexical or semantic relationship with the retrieval query, the retriever often omits them; the second challenge is that once a retriever chooses misinformation related to the query as the entities of cognitive graphs, the retriever will fail. In this study, in order to improve the performance of retrievers in complex tasks, an intelligent sensor technique was proposed based on a sub-scope with cognitive reasoning (2SCR-IR), a novel method of retrieving reasoning paths over the cognitive graph to provide users with verified multi-hop reasoning chains. Inspired by the users’ process of step-by-step searching online, 2SCR-IR includes a dynamic fusion layer that starts from the entities mentioned in the given query, explores the cognitive graph dynamically built from the query and contexts, gradually finds relevant supporting entities mentioned in the given documents, and verifies the rationality of the retrieval facts. Our experimental results show that 2SCR-IR achieves competitive results on the HotpotQA full wiki and distractor settings, and outperforms the previous state-of-the-art methods by a more than two points absolute gain on the full wiki setting

Interaction Potency of Single-Walled Carbon Nanotubes with DNAs: A Novel Assay for Assessment of Hazard Risk.

Increasing use of single-walled carbon nanotubes (SWCNTs) necessitates a novel method for hazard risk assessment. In this work, we investigated the interaction of several types of commercial SWCNTs with single-stranded (ss) and double-stranded (ds) DNA oligonucleotides (20-mer and 20 bp). Based on the results achieved, we proposed a novel assay that employed the DNA interaction potency to assess the hazard risk of SWCNTs. It was found that SWCNTs in different sizes or different batches of the same product number of SWCNTs showed dramatically different potency of interaction with DNAs. In addition, the same SWCNTs also exerted strikingly different interaction potency with ss- versus ds- DNAs. The interaction rates of SWCNTs with DNAs were investigated, which could be utilized as the indicator of potential hazard for acute exposure. Compared to solid SWCNTs, the SWCNTs dispersed in liquid medium (2% sodium cholate solution) exhibited dramatically different interaction potency with DNAs. This indicates that the exposure medium may greatly influence the subsequent toxicity and hazard risk produced by SWCNTs. Based on the findings of dose-dependences and time-dependences from the interactions between SWCNTs and DNAs, a new chemistry based assay for hazard risk assessment of nanomaterials including SWCNTs has been presented

Coordinated Scan Detection Based on Similarities of Scan Behaviors ⋆

Coordinated scan can gather host information for further attack more efficiently and stealthily than single-source port scans by distributing tasks amongst multiple sources. The existing coordinated scan detection methods are mostly based on scan behavior characteristics in temporal or spatial correlation. However, these detection methods can be easily evaded with the increasingly sophisticated coordinated scan methods. In this paper, we propose an approach to detecting coordinated scans based on the similarities between the scan behavior sequences launched by the scanners. Based on the assumption that the scanners controlled by an attacker are similar in the scan behaviors, the coordinated scan detection problem can be reduced to that of recognizing the similar scan sequences. We first present a description model of coordinated scan. Then a detection algorithm is developed based on the Dynamic Time Warping (DTW) distances between the sequences and a hierarchical clustering method was used to recognize coordinated scanners. The experimental results suggest that the proposed method has an acceptable detection rate for horizontal scans, vertical scans and hybrid scans

Typical HPLC chromatogram of the interaction of SWCNTs with the ss-DNA oligonucleotides.

<p>Carbon nanotubes: SWCNT3 (0.7–0.9 nm in diameter, 1500 in length, purity≥95%, DNA: ss-DNA oligonucleotides (RC-5-HTT), 0.015 μmole. Total volume for interaction solution: 1 mL. (A) no SWCNT3, (B) 2 mg SWCNT3, (C) 5 mg SWCNT3. Main insert: the UV spectra of suspected interaction products. Small right insert: the UV spectra of ss-DNA. Small left insert: the UV spectrum of SWCNT3 dispersed in 2% of sodium cholate solution.</p

Interaction potency data of SWCNTs with DNAs.

<p>Interaction potency data of SWCNTs with DNAs.</p

Dose-response curves for interaction of SWCNTs with DNAs.

<p>(A) DNA: ss-DNA (RC-5-HTT), 0.015 μmole. Total volume for interaction solution: 1 mL. (B) DNA: ds-DNA (ds-5-HTT), 0.015 μmole. Total volume for interaction solution: 1 mL.</p