Risk factors for bleeding after endoscopic submucosal dissection of colorectal neoplasms

AIM:To investigate the risk factors for delayed bleeding following endoscopic submucosal dissection(ESD)treatment for colorectal neoplasms.METHODS:We retrospectively reviewed the medical records of 317 consecutive patients with 325 lesions who underwent ESD for superficial colorectal neoplasms at our hospital from January 2009 to June2013.Delayed post-ESD bleeding was defined as bleeding that resulted in overt hematochezia 6 h to 30d after ESD and the observation of bleeding spots as confirmed by repeat colonoscopy or a required blood transfusion.We analyzed the relationship between risk factors for delayed bleeding following ESD and the following factors using univariate and multivariate analyses:age,gender,presence of comorbidities,use of antithrombotic drugs,use of intravenous heparin,resected specimen size,lesion size,lesion location,lesion morphology,lesion histology,the device used,procedure time,and the presence of significant bleeding during ESD.RESULTS:Delayed post-ESD bleeding was found in14 lesions from 14 patients(4.3%of all specimens,4.4%patients).Patients with episodes of delayed postESD bleeding had a mean hemoglobin decrease of2.35 g/dL.All episodes were treated successfully using endoscopic hemostatic clips.Emergency surgery was not required in any of the cases.Blood transfusion was needed in 1 patient(0.3%).Univariate analysis revealed that lesions located in the cecum(P=0.012)and the presence of significant bleeding during ESD(P=0.024)were significantly associated with delayed post-ESD bleeding.The risk of delayed bleeding was higher for larger lesion sizes,but this trend was not statistically significant.Multivariate analysis revealed that lesions located in the cecum(OR=7.26,95%CI:1.99-26.55,P=0.003)and the presence of significant bleeding during ESD(OR=16.41,95%CI:2.60-103.68,P=0.003)were independent risk factors for delayed post-ESD bleeding.CONCLUSION:Location in the cecum and significant bleeding during ESD predispose patients to delayed post-procedural bleeding.Therefore,careful and additional management is recommended for these patients.

Inhibition of DNA-Topoisomerase I by Acylated Triterpene Saponins from Pittosporum angustifolium Lodd.

Previous phytochemical investigation of the leaves and seeds of Pittosporum angustifolium Lodd.led to the isolation and structural elucidation of polyphenols and triterpene saponins.Evaluation for cytotoxicity of isolated saponins revealed that the predominant structural feature for a cytotoxic activity are acyl substituents at the oleanane aglycon backbone.The present work reports the results of a screening of 10 selected acylated saponins for their potential to inhibit the human DNA-topoisomerase I,giving rise to IC50 values in a range of 2.8-46.5 lM.To clarify the mode of observed cytotoxic action and,moreover,to distinguish from a pure surfactant effect which is commonly accompanied with saponins,these results indicate an involvement of the topoisomerase I and its role as a possible target structure for a cytotoxic activity.In addition,computational predictions of the fitting of saponins to the topoisomerase I-DNA complex,indicate a similar binding mode to that of clinically used topoisomerase I inhibitors.Graphical Abstract Ten acylated triterpene saponins from Pittosporum angustifolium were investigated for their potential to inhibit the human DNA-topoisomerase I and computational predictions of the fitting of saponins to the topoisomerase I-DNA complex were carried out.

Epidemiology and Mutational Analysis of Global Strains of Crimean-Congo Haemorrhagic Fever Virus

Crimean-Congo hemorrhagic fever (CCHF) is a severe illness with high fatality.Cases are reported in several countries in Africa,Europe,the Middle East,and Asia.Phylogenetic analyses based on the virus S (nucleocapsid),M (glycoprotein),and L (polymerase) genome segments sequences indicate distinct geographic lineages exist but their specific genetic characteristics require elucidation.In this work we collected all full length S segment sequences and generated a phylogenetic tree based on the alignment of these 62 samples.We then analyzed the alignment using entries from AAIndex,the Amino Acid Index database,to identify amino acid mutations that performed significant changes in charge,pka,hydropathy and side chain volume.Finally,we mapped these changes back to the tree and alignment to identify correlated mutations or sites that characterized a specific lineage.Based on this analysis we are able to propose a number of sites that appear to be important for virus function and which would be good candidates for experimental mutational analysis studies.

Impact of weather variables on mosquitoes infected with Japanese encephalitis virus in Kurnool district,Andhra Pradesh

Objective:To assess the virus infection in mosquitoes during different seasons and correlated with various climatic factors.Methods:The field collected vectors were screened for Japanese encephalitis(JE) virus after dessication using ELISA method.Most of the positive pools were recorded from Culex tritaeniorhynchus(Cx.tritaeniorhynchus) and Culex.gelidus(Cx.gelidus) during JE transmission season(winter) and some positive pools were also reported during non JE transmission periods(i.e.summer and rainy seasons).Results:The minimum infection rates(MIR) of 1.75 from Cx.tritaeniorhynchus and 0.17 from Cx.gelidus has been reported in the year 2002 at the beginning of the study and the values were found nil at the end of the study(2006) from the study areas of Kurnool district.Conclusions:From this study it is noted that MTR of Cx.gelidus and Cx.tritaeniorhynchus were modulated by various meteorological parameters.The mosquito vector abundance increases after the monsoon period(winter) and lowest in dry season(summer). Similarly,MIR fluctuated between seasons with higher MIR recorded after monsoon period and lower in the rest of season.Impact of these metrological parameters in JE virus infected mosquitoes is discussed in this paper.

In silico modification of oseltamivir as neuraminidase inhibitor of influenza A virus subtype H1N1

This research focused on the modification of the functional groups of oseltamivir as neuraminidase inhibitor against influenza A virus subtype H1N1.Interactions of three of the best ligands were evaluated in the hydrated state using molecular dynamics simulation at two different temperatures.The docking result showed that AD3BF2 D ligand（N-[（1S,6R）-5-amino-5-{[（2R,3S,4S）-3,4-dihydroxy-4-（hydroxymethyl） tetrahydrofuran-2-yl]oxy}-4-formylcyclohex-3-en-1-yl]acetamide-3-（1-ethylpropoxy）-1-cyclohexene-1-carboxylate） had better binding energy values than standard oseltamivir.AD3BF2 D had several interactions,including hydrogen bonds,with the residues in the catalytic site of neuraminidase as identified by molecular dynamics simulation.The results showed that AD3BF2 D ligand can be used as a good candidate for neuraminidase inhibitor to cope with influenza A virus subtype H1N1.

microRNA的功能(英文)

MicroRNAs(miRNAs)are a class of small non-coding RNAs that play important roles in post-transcriptional regulation of gene expression[1].A large number of miRNAs have been found to be involved in a broad spectrum of biological functions such as regulation of innate and adaptive immunity,cell differentiation and development as well as

MicroPath-A pathway-based pipeline for the comparison of multiple gene expression profiles to identify common biological signatures

High throughput gene expression analysis is swiftly becoming the focal point for deciphering molecular mechanisms underlying various dif-ferent biological questions. Testament to this is the fact that vast volumes of expression profiles are being generated rapidly by scientists worldwide and subsequently stored in publicly available data repositories such as ArrayEx-press and the Gene Expression Omnibus (GEO). Such wealth of biological data has motivated biologists to compare expression profiles gen-erated from biologically-related microarray ex-periments in order to unravel biological mecha-nisms underlying various states of diseases. However, without the availability of appropriate software and tools, they are compelled to use manual or labour-intensive methods of com-parisons. A scrutiny of current literature makes it apparent that there is a soaring need for such bioinformatics tools that cater for the multiple analyses of expression profiles. In order to contribute towards this need, we have developed an efficient software pipeline for the analysis of multiple gene expression data-sets, called Micropath, which implements three principal functions;1) it searches for common genes amongst n number of datasets using a number crunching method of comparison as well as applying the principle of permutations and combinations in the form of a search strat-egy, 2) it extracts gene expression patterns both graphically and statistically, and 3) it streams co-expressed genes to all molecular pathways belonging to KEGG in a live fashion. We sub-jected MicroPath to several expression datasets generated from our tolerance-related in-house microarray experiments as well as published data and identified a set of 31 candidate genes that were found to be co-expressed across all interesting datasets. Pathway analysis revealed their putative roles in regulating immune toler-ance. MicroPath is freely available to download from: www.1066technologies.co.uk/micropath.

Corrigendum to“Antibiotic Treatment Drives the Diversification of the Human Gut Resistome”[Genomics Proteomics Bioinformatics 17(1)(2019)39-51]

The editors regret there was an error in“Shotgun metagenome library construction and sequencing”section.“The raw sequences can be found in BGID(CRA000815)”should be corrected to“The raw metagenome sequencing data have been deposited in the Genome Sequence Archive at Beijing Institute of Genomics,Chinese Academy of Sciences(GSA:CRA000815),and are publicly accessible at https://bigd.big.ac.cn/gsa/”.The correct section is shown below.The editors would like to apologize for any inconvenience caused.

Induction of desiccation tolerance in desiccation sensitive Citrus limon seeds

Many economically important perennial species bear recalcitrant seeds, including tea, coffee, cocoa, mango,citrus, rubber, oil palm and coconut. Orthodox seeds can be dried almost completely without losing viability, but so-called recalcitrant seeds have a very limited storage life and die upon drying below a higher critical moisture content than orthodox seeds. As a result, the development of longterm storage methods for recalcitrant seeds is compromised.Lowering this critical moisture content would be very valuable since dry seed storage is the safest, most convenient and cheapest method for conserving plant genetic resources.Therefore, we have attempted to induce desiccation tolerance(DT) in the desiccation sensitive seeds of Citrus limon. We show that DT can be induced by paclobutrazol(an inhibitor of gibberellin biosynthesis) and we studied its associated transcriptome to delineate the molecular mechanisms underlying this induction of DT. Paclobutrazol not only interfered with gibberellin related gene expression but also caused extensive changes in expression of genes involved in the biosynthesis and signaling of other hormones. Paclobutrazol induced a transcriptomic switch encompassing suppression of biotic-and induction of abiotic responses.We hypothesize that this is the main driver of the induction of DT by paclobutrazol in C. limon seeds.

DNA Extraction Protocol for Biological Ingredient Analysis of Liuwei Dihuang Wan

Traditional Chinese medicine （TCM） clinical practice. So far, the methods commonly preparations are widely used for healthcare and used for quality evaluation of TCM preparations mainly focused on chemical ingredients. The biological ingredient analysis of TCM preparations is also important because TCM preparations usually contain both plant and animal ingredients, which often include some mis-identified herbal materials, adulterants or even some biological contaminants. For biological ingredient analysis, the efficiency of DNA extraction is an important factor which might affect the accuracy and reliability of identification. The component complexity in TCM preparations is high, and DNA might be destroyed or degraded in different degrees after a series of processing procedures. Therefore, it is necessary to establish an effective protocol for DNA extraction from TCM preparations. In this study, we chose a classical TCM preparation, Liuwei Dihuang Wan （LDW）, as an example to develop a TCM-specific DNA extraction method. An optimized cetyl trimethyl ammonium bromide （CTAB） method （TCM-CTAB） and three commonly-used extraction kits were tested for extraction of DNA from LDW samples. Experimental results indicated that DNA with the highest purity and concentration was obtained by using TCM-CTAB. To further evaluate the different extraction methods, amplification of the second internal transcribed spacer （ITS2） and the chloroplast genome trnL intron was carried out.

Systematic study of human long intergenic non-coding RNAs and their impact on cancer

The functional impact of several long intergenic non-coding RNAs (lincRNAs) has been characterized in previous studies. However, it is difficult to identify lincRNAs on a large-scale and to ascertain their functions or predict their structures in laboratory experiments because of the diversity, lack of knowledge and specificity of expression of lincRNAs. Furthermore, although there are a few well-characterized examples of lincRNAs associated with cancers, these are just the tip of the iceberg owing to the complexity of cancer. Here, by combining RNA-Seq data from several kinds of human cell lines with chromatin-state maps and human expressed sequence tags, we successfully identified more than 3000 human lincRNAs, most of which were new ones. Subsequently, we predicted the functions of 105 lincRNAs based on a coding-non-coding gene co-expression network. Finally, we propose a genetic mediator and key regulator model to unveil the subtle relationships between lincRNAs and lung cancer. Twelve lincRNAs may be principal players in lung tumorigenesis. The present study combines large-scale identification and functional prediction of human lincRNAs, and is a pioneering work in characterizing cancer-associated lincRNAs by bioinformatics.

Antibiotic Treatment Drives the Diversification of the Human Gut Resistome

Despite the documented antibiotic-induced disruption of the gut microbiota, the impact of antibiotic intake on strain-level dynamics, evolution of resistance genes, and factors influencing resistance dissemination potential remains poorly understood. To address this gap we analyzed public metagenomic datasets from 24 antibiotic treated subjects and controls, combined with an in-depth prospective functional study with two subjects investigating the bacterial community dynamics based on cultivation-dependent and independent methods. We observed that shortterm antibiotic treatment shifted and diversified the resistome composition, increased the average copy number of antibiotic resistance genes, and altered the dominant strain genotypes in an individual-specific manner. More than 30% of the resistance genes underwent strong differentiation at the single nucleotide level during antibiotic treatment. We found that the increased potential for horizontal gene transfer, due to antibiotic administration, was ～3-fold stronger in the differentiated resistance genes than the non-differentiated ones. This study highlights how antibiotic treatment has individualized impacts on the resistome and strain level composition, and drives the adaptive evolution of the gut microbiota.

Dev Cell:科学家阐明人类胚胎原生殖细胞发育的分子机制

近日,刊登于国际杂志Developmental Cell上的一项研究报道中，来自巴布拉汉研究所（Babraham Insdtute）的研究人员通过研究调查了原生殖细胞发育的早期阶段，同时他们在实验室开发了一种产生类似细胞的策略，这种酷似人类原始生殖细胞的产生对于未来生殖领域的研究，以及分析人类潜在的继代基因调控的遗传机制非常重要。

Large-scale study of long non-coding RNA functions based on structure and expression features

Mammals and other complex organisms can transcribe an abundance of long non-coding RNAs(lncRNAs)that fulfill a wide variety of regulatory roles in many biological processes.These roles,including as scaffolds and as guides for protein-coding genes,mainly depend on the structure and expression level of lncRNAs.In this review,we focus on the current methods for analyzing lncRNA structure and expression,which is basic but necessary information for in-depth,large-scale analysis of lncRNA functions.

Galaxy:A Decade of Realising CWFR Concepts

Despite recent encouragement to follow the FAIR principles,the day-to-day research practices have not changed substantially.Due to new developments and the increasing pressure to apply best practices,initiatives to improve the efficiency and reproducibility of scientific workflows are becoming more prevalent.In this article,we discuss the importance of well-annotated tools and the specific requirements to ensure reproducible research with FAIR outputs.We detail how Galaxy,an open-source workflow management system with a web-based interface,has implemented the concepts that are put forward by the Canonical Workflow Framework for Research(CWFR),whilst minimising changes to the practices of scientific communities.Although we showcase concrete applications from two different domains,this approach is generalisable to any domain and particularly useful in interdisciplinary research and science-based applications.

Application of Meta-Mesh on the analysis of microbial communities from human associated-habitats

With the current fast accumulation of microbial community samples and related metagenomic sequencing data, data integration and analysis system is urgently needed for in-depth analysis of large number of metagenomic samples （also referred to as ＂microbial communities＂） of interest. Although several existing databases have collected a large number of metagenomie samples, they mostly serve as data repositories with crude annotations, and offer limited functionality for analysis. Moreover, the few available tools for comparative analysis in the literature could only support the comparison of a few pre-defined set of metagenomic samples. To facilitate comprehensive comparative analysis on large amount of diverse microbial community samples, we have designed a Meta-Mesh system for a variety of analyses including quantitative analysis of similarities among microbial communities and computation of the correlation between the meta-information of these samples. We have used Meta-Mesh for systematically and efficiently analyses on diverse sets of human associate-habitat microbial community samples. Results have shown that Meta-Mesh could serve well as an efficient data analysis platform for discovery of clusters, biomarker and other valuable biological information from a large pool of human microbial samples.

Progression and prospects of translational medicine in China

Translational medicine is a new discipline aiming to eliminate the barrier between preclinical and clinical medicine [1]. It converts promising laboratory discoveries into clinical applications and elucidates clinical questions

CloudLCA: finding the lowest common ancestor in metagenome analysis using cloud computing

Estimating taxonomic content constitutes a key problem in metagenomic sequencing data analysis.However,extracting such content from high-throughput data of next-generation sequencing is very time-consuming with the currently available software.Here,we present CloudLCA,a parallel LCA algorithm that significantly improves the efficiency of determining taxonomic composition in metagenomic data analysis.Results show that CloudLCA(1)has a running time nearly linear with the increase of dataset magnitude,(2)displays linear speedup as the number of processors grows,especially for large datasets,and(3)reaches a speed of nearly 215 million reads each minute on a cluster with ten thin nodes.In comparison with MEGAN,a well-known metagenome analyzer,the speed of CloudLCA is up to 5 more times faster,and its peak memory usage is approximately 18.5%that of MEGAN,running on a fat node.CloudLCA can be run on one multiprocessor node or a cluster.It is expected to be part of MEGAN to accelerate analyzing reads,with the same output generated as MEGAN,which can be import into MEGAN in a direct way to finish the following analysis.Moreover,CloudLCA is a universal solution for finding the lowest common ancestor,and it can be applied in other fields requiring an LCA algorithm.

SYSTEMS BIOLOGY BRINGS LIFE SCIENCES CLOSER—REPORT ON THE CHINA-UK SYSTEMS BIOLOGY WORKSHOP 2005

The China-UK Systems held during June 20-21 Biology Workshop 2005 was in the National Science Park of Zhejiang University, Hangzhou, China. It was organized by the Institute of Bioinformatics, Zhejiang University, and was initiated by Prof. Dr. Jun Zhu （Zhejiang University） and Prof. Dr. John Findlay （University of Leeds, UK）. The workshop was part of the program called UK-China Partners in Science, a one-year campaign that was initiated by the British government to explore more collaborations between UK and China on science and technology. It was attended also by a representative of this program, Mr. Frank Yuan, senior science ＆ innovation officer. The idea of the workshop was to bring together experts with specialists in systems biology in order to promote the ＂natural partnership＂ between scientists from the two countries. The most important items of systcms biology considered at the workshop were： （1） New technologies and advances in systems biology; （2） Research developments in genomics and proteomics; （3） New methodologies and software in computational biology; （4） Research collaboration on systems biology between China and UK.

U7 snRNAs:A Computational Survey

U7 small nuclear RNA （snRNA） sequences have been described only for a handful of animal species in the past. Here we describe a computational search for functional U7 snRNA genes throughout vertebrates including the upstream sequence elements characteristic for snRNAs transcribed by polymerase Ⅱ. Based on the results of this search, we discuss the high variability of U7 snRNAs in both sequence and structure, and report on an attempt to find U7 snRNA sequences in basal deuterostomes and non-drosophilids insect genomes based on a combination of sequence, structure, and promoter features. Due to the extremely short sequence and the high variability in both sequence and structure, no unambiguous candidates were found. These results cast doubt on putative U7 homologs in even more distant organisms that are reported in the most recent release of the Rfam database.