Publications by authors named "Xiao-Chen Bo"

25 Publications

  • Page 1 of 1

Genomic elucidation of a COVID-19 resurgence and local transmission of SARS-CoV-2 in Guangzhou, China.

J Clin Microbiol 2021 May 5. Epub 2021 May 5.

Beijing Institute of Radiation Medicine, Beijing, China

While China experienced a peak and decline in coronavirus disease 2019 (COVID-19) cases at the start of 2020, in subsequent months, regional outbreaks have continuously emerged. Resurgences of COVID-19 have also been observed in many other countries. In Guangzhou, China, a small outbreak, involving less than 100 residents, emerged in March and April 2020, and comprehensive and near-real-time genomic surveillance of SARS-CoV-2 was conducted. When the numbers of confirmed cases among overseas travelers increased, public health measures were enhanced by shifting from self-quarantine to central quarantine and SARS-CoV-2 testing for all overseas travelers. In an analysis of 109 imported cases, we found diverse viral variants distributed in the global viral phylogeny, which were frequently shared within households but not among passengers on the same flight. In contrast to the viral diversity of imported cases, local transmission was predominately attributed to two specific variants imported from Africa, including local cases that reported no direct or indirect contact with imported cases. The introduction events of the virus were identified or deduced before the enhanced measures were taken. These results show that the interventions were effective in containing the spread of SARS-CoV-2, and they ruled out the possibility of cryptic transmission of viral variants from the first wave in January and February 2020. Our study provides evidence and emphasizes the importance of controls for overseas travelers in the context of the pandemic and exemplifies how viral genomic data can facilitate COVID-19 surveillance and inform public health mitigation strategies.
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http://dx.doi.org/10.1128/JCM.00079-21DOI Listing
May 2021

Forensic nanopore sequencing of STRs and SNPs using Verogen's ForenSeq DNA Signature Prep Kit and MinION.

Int J Legal Med 2021 May 5. Epub 2021 May 5.

School of Forensic Medicine, Shanxi Medical University, Taiyuan, 030001, People's Republic of China.

The MinION nanopore sequencing device (Oxford Nanopore Technologies, Oxford, UK) is the smallest commercially available sequencer and can be used outside of conventional laboratories. The use of the MinION for forensic applications, however, is hindered by the high error rate of nanopore sequencing. One approach to solving this problem is to identify forensic genetic markers that can consistently be typed correctly based on nanopore sequencing. In this pilot study, we explored the use of nanopore sequencing for single nucleotide polymorphism (SNP) and short tandem repeat (STR) profiling using Verogen's (San Diego, CA, USA) ForenSeq DNA Signature Prep Kit. Thirty single-contributor samples and DNA standard material 2800 M were genotyped using the Illumina (San Diego, CA, USA) MiSeq FGx and MinION (with R9.4.1 flow cells) devices. With an optimized cutoff for allelic imbalance, all 94 identity-informative SNP loci could be genotyped reliably using the MinION device, with an overall accuracy of 99.958% (1 error among 2926 genotypes). STR typing was notably error prone, and its accuracy was locus dependent. We developed a custom-made bioinformatics workflow, and finally selected 13 autosomal STRs, 14 Y-STRs, and 4 X-STRs showing high consistency between nanopore and Illumina sequencing among the tested samples. These SNP and STR loci could be candidates for panel design for forensic analysis based on nanopore sequencing.
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http://dx.doi.org/10.1007/s00414-021-02604-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098014PMC
May 2021

N-Methyladenine DNA Modification in the Human Genome.

Mol Cell 2018 07 12;71(2):306-318.e7. Epub 2018 Jul 12.

Biomedicine Research Center, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China; Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China. Electronic address:

DNA N-methyladenine (6mA) modification is the most prevalent DNA modification in prokaryotes, but whether it exists in human cells and whether it plays a role in human diseases remain enigmatic. Here, we showed that 6mA is extensively present in the human genome, and we cataloged 881,240 6mA sites accounting for ∼0.051% of the total adenines. [G/C]AGG[C/T] was the most significantly associated motif with 6mA modification. 6mA sites were enriched in the coding regions and mark actively transcribed genes in human cells. DNA 6mA and N-demethyladenine modification in the human genome were mediated by methyltransferase N6AMT1 and demethylase ALKBH1, respectively. The abundance of 6mA was significantly lower in cancers, accompanied by decreased N6AMT1 and increased ALKBH1 levels, and downregulation of 6mA modification levels promoted tumorigenesis. Collectively, our results demonstrate that DNA 6mA modification is extensively present in human cells and the decrease of genomic DNA 6mA promotes human tumorigenesis.
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http://dx.doi.org/10.1016/j.molcel.2018.06.015DOI Listing
July 2018

Biological data processing based on bio-processor unit (BPU), a new concept for next generation computational biology.

Sci China Life Sci 2018 05 12;61(5):597-598. Epub 2018 Mar 12.

State Key Laboratory of Mathematical Engineering and Advanced Computation, Wuxi, 214122, China.

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http://dx.doi.org/10.1007/s11427-018-9278-3DOI Listing
May 2018

A 472-SNP panel for pairwise kinship testing of second-degree relatives.

Forensic Sci Int Genet 2018 05 2;34:178-185. Epub 2018 Mar 2.

Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, China. Electronic address:

Kinship testing based on genetic markers, as forensic short tandem repeats (STRs) and single nucleotide polymorphisms (SNPs), has valuable practical applications. Paternity and first-degree relationship can be accurately identified by current commonly-used forensic STRs and reported SNP markers. However, second-degree and more distant relationships remain challenging. Although ∼10-10 SNPs can be used to estimate relatedness of higher degrees, genome-wide genotyping and analysis may be impractical for forensic use. With rapid growth of human genome data sets, it is worthwhile to explore additional markers, especially SNPs, for kinship analysis. Here, we reported an autosomal SNP panel consisted of 342 SNP selected from >84 million SNPs and 131 SNPs from previous systems. We genotyped these SNPs in 136 Chinese individuals by multiplex amplicon Massively Parallel Sequencing, and performed pairwise gender-independent kinship testing. The specificity and sensitivity of these SNPs to distinguish second-degree relatives and the unrelated was 99.9% and 100%, respectively, compared with 53.7% and 99.9% of 19 commonly-used forensic STRs. Moreover, the specificity increased to 100% by the combined use of these STRs and SNPs. The 472-SNP panel could also greatly facilitate the discrimination among different relationships. We estimated that the power of ∼6.45 SNPs were equivalent to one forensic STR in the scenario of 2nd-degree relative pedigree. Altogether, we proposed a panel of 472 SNP markers for kinship analysis, which could be important supplementary of current forensic STRs to solve the problem of second-degree relative testing.
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http://dx.doi.org/10.1016/j.fsigen.2018.02.019DOI Listing
May 2018

Partners of patients with ulcerative colitis exhibit a biologically relevant dysbiosis in fecal microbial metacommunities.

World J Gastroenterol 2017 Jul;23(25):4624-4631

Guang-Lan Chen, Ye Zhang, Wang-Yue Wang, Xue-Liang Ji, Department of Gastroenterology, Lishui People's Hospital, Lishui 323000, Zhejiang Province, China.

Aim: To investigate alterations in the fecal microbiome using 16S rRNA amplicon sequencing in couples in the same cohabitation environment.

Methods: Fecal samples were collected from eight ulcerative colitis (UC) patients and their healthy partners at Lishui People's Hospital, Zhejiang Province, China. DNA was extracted and the variable regions V3 and V4 of the 16S rRNA genes were PCR amplified using a two-step protocol. Clear reads were clustered into operational taxonomic units (OTUs) at the 97% sequence similarity level using UCLUST v1.2.22. The Wilcoxon rank-sum test (R v3.1.2) was used to compare inter-individual differences. Differences with a value < 0.05 were considered statistically significant.

Results: Fecal microbial communities were more similar among UC patients than their healthy partners ( = 0.024). UC individuals had a lower relative abundance of bacteria belonging to the , especially , , and ( < 0.05). Microbiota dysbiosis was detected in UC patients and their healthy partners. Relevant genera included , , , , and . The enriched pathways in fecal samples of UC patients were related to lipid and nucleotide metabolism. Additionally, the pathways involved in membrane transport and metabolism of cofactors and vitamins were more abundant in the healthy partners.

Conclusion: Our results suggested that the microbial composition might be affected in healthy partners cohabiting with UC patients, especially in terms of microbiota dysbiosis.
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http://dx.doi.org/10.3748/wjg.v23.i25.4624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5504378PMC
July 2017

Intra-host dynamics of Ebola virus during 2014.

Nat Microbiol 2016 Sep 5;1(11):16151. Epub 2016 Sep 5.

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.

Since 2013, West Africa has encountered the largest Ebola virus (EBOV) disease outbreak on record, and Sierra Leone is the worst-affected country, with nearly half of the infections. By means of next-generation sequencing and phylogeographic analysis, the epidemiology and transmission of EBOV have been well elucidated. However, the intra-host dynamics that mainly reflect viral-host interactions still need to be studied. Here, we show a total of 710 intra-host single nucleotide variations (iSNVs) from deep-sequenced samples from EBOV-infected patients, through a well-tailored bioinformatics pipeline. We present a comprehensive distribution of iSNVs during this outbreak and along the EBOV genome. Analyses of iSNV and its allele frequency reveal that VP40 is the most conserved gene during this outbreak, and thus it would be an ideal therapeutic target. In the co-occurring iSNV network, varied iSNV sites present different selection features. Intriguingly, the T-to-C substitutions at the 3'-UTR of the nucleoprotein (NP; positions 3008 and 3011), observed in many patients, result in the upregulation of the transcription of NP through an Ebola mini-genome reporting system. Additionally, no iSNV enrichment within B-cell epitopes of GP has been observed.
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http://dx.doi.org/10.1038/nmicrobiol.2016.151DOI Listing
September 2016

Neuroendocrine immunomodulation network dysfunction in SAMP8 mice and PrP-hAβPPswe/PS1ΔE9 mice: potential mechanism underlying cognitive impairment.

Oncotarget 2016 Apr;7(17):22988-3005

Department of Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing, China.

Senescence-accelerated mouse prone 8 strain (SAMP8) and PrP-hAβPPswe/PS1ΔE9 (APP/PS1) mice are classic animal models of sporadic Alzheimer's disease and familial AD respectively. Our study showed that object recognition memory, spatial learning and memory, active and passive avoidance were deteriorated and neuroendocrine immunomodulation (NIM) network was imbalance in SAMP8 and APP/PS1 mice. SAMP8 and APP/PS1 mice had their own specific phenotype of cognition, neuroendocrine, immune and NIM molecular network. The endocrine hormone corticosterone, luteinizing hormone and follicle-stimulating hormone, chemotactic factor monocyte chemotactic protein-1, macrophage inflammatory protein-1β, regulated upon activation normal T cell expressed and secreted factor and eotaxin, pro-inflammatory factor interleukin-23, and the Th1 cell acting as cell immunity accounted for cognitive deficiencies in SAMP8 mice, while adrenocorticotropic hormone and gonadotropin-releasing hormone, colony stimulating factor granulocyte colony stimulating factor, and Th2 cell acting as humoral immunity in APP/PS1 mice. On the pathway level, chemokine signaling and T cell receptor signaling pathway played the key role in cognition impairments of two models, while cytokine-cytokine receptor interaction and natural killer cell mediated cytotoxicity were more important in cognitive deterioration of SAMP8 mice than APP/PS1 mice. This mechanisms of NIM network underlying cognitive impairment is significant for further understanding the pathogenesis of AD and can provide useful information for development of AD therapeutic drug.
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http://dx.doi.org/10.18632/oncotarget.8453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029605PMC
April 2016

Exploring the efficacy of paternity and kinship testing based on single nucleotide polymorphisms.

Forensic Sci Int Genet 2016 May 27;22:161-168. Epub 2016 Feb 27.

Department of Biotechnology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, People's Republic of China. Electronic address:

Short tandem repeats (STRs) are conventional genetic markers typically used for paternity and kinship testing. As supplementary markers of STRs, single nucleotide polymorphisms (SNPs) have less discrimination power but broader applicability to degraded samples. The rapid improvement of next-generation sequencing (NGS) and multiplex amplification technologies also make it possible now to simultaneously identify dozens or even hundreds of SNP loci in a single pool. However, few studies have been endeavored to kinship testing based on SNP loci. In this study, we genotyped 90 autosomal human identity SNP loci with NGS, and investigated their testing efficacies based on the likelihood ratio model in eight pedigree scenarios involving paternity, half/full-sibling, uncle/nephew, and first-cousin relationships. We found that these SNPs might be sufficient to discriminate paternity and full-sibling, but impractical for more distant relatives such as uncle and cousin. Furthermore, we conducted an in silico study to obtain the theoretical tendency of how testing efficacy varied with increasing number of SNP loci. For each testing battery in a given pedigree scenario, we obtained distributions of logarithmic likelihood ratio for both simulated relatives and unrelated controls. The proportion of the overlapping area between the two distributions was defined as a false testing level (FTL) to evaluate the testing efficacy. We estimated that 85, 127, 491, and 1,858 putative SNP loci were required to discriminate paternity, full-sibling, half-sibling/uncle-nephew, and first-cousin (FTL, 0.1%), respectively. To test a half-sibling or nephew, an additional uncle relative could be included to decrease the required number of putative SNP loci to ∼320 (FTL, 0.1%). As a systematic computation of paternity and kinship testing based only on SNPs, our results could be informative for further studies and applications on paternity and kinship testing using SNP loci.
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http://dx.doi.org/10.1016/j.fsigen.2016.02.012DOI Listing
May 2016

A Co-Module Regulated by Therapeutic Drugs in a Molecular Subnetwork of Alzheimer's Disease Identified on the Basis of Traditional Chinese Medicine and SAMP8 Mice.

Curr Alzheimer Res 2015 ;12(9):870-85

Department of TCM and Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.

There are currently no approved effective therapies for Alzheimer's disease (AD). AD is a classic, multifactorial, complex syndrome. Thus, a polypharmacological or multitargeted approach to AD might provide better therapeutic benefits than monotherapies. However, it remains elusive which biological processes and biomolecules involved in the pathophysiologic processes of AD would constitute good targets for multitargeted therapy. This study proposes that a co-module, consisting of biological processes, cellular pathways and nodes, in a molecular subnetwork perturbed by different therapeutic drugs may be the optimal therapeutic target for an AD multitarget-based intervention. Based on this hypothesis, genes regulated in the hippocampus and cortex of senescence-accelerated mouse prone-8 (SAMP8) mice by traditional Chinese medicine (TCM) prescriptions with different constituents and the same beneficial effects on AD, including the decoctions Liu-Wei-Di-Huang (LW), Ba-Wei-Di-Huang (BW), Danggui-Shaoyao-San (DSS), Huang-Lian-Jie-Du (HL) and Tiao-Xin-Fang (TXF), were investigated via cDNA microarray, and the perturbed subnetworks were constructed and interpreted. After comparing 15 perturbed subnetworks based on genes affected by LW, BW, HL, DSS and TXF, the results showed that the most important common nodes perturbed by these interventions in the brains of SAMP8 mice were RPS6KA1 and FHIT, and that other important common nodes included UBE2D2, STUB1 and AMFR. These five drugs simultaneously and significantly disturbed the regulation of apoptosis and protein ubiquitination among biological processes. These nodes and processes were key components of the co-module regulated by therapeutic drugs in a molecular subnetwork of AD. These results suggest that targeting candidate regulator of apoptosis and protein ubiquitination might be effective for AD treatment, and that RPS6KA1, FHIT, UBE2D2, STUB1 and AMFR might be optimal combinational targets of an AD multitarget-based therapy.
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http://dx.doi.org/10.2174/1567205012666150710111858DOI Listing
August 2016

Genetic diversity and evolutionary dynamics of Ebola virus in Sierra Leone.

Nature 2015 Aug 13;524(7563):93-6. Epub 2015 May 13.

Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130122, China.

A novel Ebola virus (EBOV) first identified in March 2014 has infected more than 25,000 people in West Africa, resulting in more than 10,000 deaths. Preliminary analyses of genome sequences of 81 EBOV collected from March to June 2014 from Guinea and Sierra Leone suggest that the 2014 EBOV originated from an independent transmission event from its natural reservoir followed by sustained human-to-human infections. It has been reported that the EBOV genome variation might have an effect on the efficacy of sequence-based virus detection and candidate therapeutics. However, only limited viral information has been available since July 2014, when the outbreak entered a rapid growth phase. Here we describe 175 full-length EBOV genome sequences from five severely stricken districts in Sierra Leone from 28 September to 11 November 2014. We found that the 2014 EBOV has become more phylogenetically and genetically diverse from July to November 2014, characterized by the emergence of multiple novel lineages. The substitution rate for the 2014 EBOV was estimated to be 1.23 × 10(-3) substitutions per site per year (95% highest posterior density interval, 1.04 × 10(-3) to 1.41 × 10(-3) substitutions per site per year), approximating to that observed between previous EBOV outbreaks. The sharp increase in genetic diversity of the 2014 EBOV warrants extensive EBOV surveillance in Sierra Leone, Guinea and Liberia to better understand the viral evolution and transmission dynamics of the ongoing outbreak. These data will facilitate the international efforts to develop vaccines and therapeutics.
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http://dx.doi.org/10.1038/nature14490DOI Listing
August 2015

Nodes and biological processes identified on the basis of network analysis in the brain of the senescence accelerated mice as an Alzheimer's disease animal model.

Front Aging Neurosci 2013 29;5:65. Epub 2013 Oct 29.

Department of Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology Beijing, China.

Harboring the behavioral and histopathological signatures of Alzheimer's disease (AD), senescence accelerated mouse-prone 8 (SAMP8) mice are currently considered a robust model for studying AD. However, the underlying mechanisms, prioritized pathways and genes in SAMP8 mice linked to AD remain unclear. In this study, we provide a biological interpretation of the molecular underpinnings of SAMP8 mice. Our results were derived from differentially expressed genes in the hippocampus and cerebral cortex of SAMP8 mice compared to age-matched SAMR1 mice at 2, 6, and 12 months of age using cDNA microarray analysis. On the basis of PPI, MetaCore and the co-expression network, we constructed a distinct genetic sub-network in the brains of SAMP8 mice. Next, we determined that the regulation of synaptic transmission and apoptosis were disrupted in the brains of SAMP8 mice. We found abnormal gene expression of RAF1, MAPT, PTGS2, CDKN2A, CAMK2A, NTRK2, AGER, ADRBK1, MCM3AP, and STUB1, which may have initiated the dysfunction of biological processes in the brains of SAMP8 mice. Specifically, we found microRNAs, including miR-20a, miR-17, miR-34a, miR-155, miR-18a, miR-22, miR-26a, miR-101, miR-106b, and miR-125b, that might regulate the expression of nodes in the sub-network. Taken together, these results provide new insights into the biological and genetic mechanisms of SAMP8 mice and add an important dimension to our understanding of the neuro-pathogenesis in SAMP8 mice from a systems perspective.
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http://dx.doi.org/10.3389/fnagi.2013.00065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3810591PMC
November 2013

[Screening for genes associated with cardiac fibrosis induced by aldosterone].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2012 Apr;28(4):350-3

Department of Cardiology, PLA General Hospital, Beijing 100853, China.

Aim: To investigate differently expressed genes associated with cardiac fibrosis induced independently by aldosterone.

Methods: Fetal cardiac fibroblasts (FCFs)were isolated and cultured. Total RNA was extracted 8 hours after aldosterone administration. Then gene chips were used to screen these RNA samples. Some of candidate genes were confirmed by RT-PCR and Western blot.

Results: Differently expressed 1519 genes were screened. Up-regulated genes were 714 while down-regulated genes were 805. The expression of CCL7, MMP-26 and IL31RA was tested by RT-PCR and western blot, the results is identical with those by gene chips.

Conclusion: Gene chip can efficiently single out differently expressed genes induced dependently by aldosterone in FCFs. CCL7, MMP-26 and IL31RA may be associated with cardiac fibrosis induced by aldosterone.
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April 2012

Cellular microRNA let-7c inhibits M1 protein expression of the H1N1 influenza A virus in infected human lung epithelial cells.

J Cell Mol Med 2012 Oct;16(10):2539-46

Lab of Biotechnology, Beijing Institute of Radiation Medicine, Beijing, China.

The influenza virus (IV) triggers a series of signalling events inside host cells and induces complex cellular responses. Studies have suggested that host factors play an essential role in IV replication. MicroRNAs (miRNAs) represent a class of small non-coding RNAs that target mRNAs, triggering either translation repression or RNA degradation. Emerging research suggests that host-derived cellular miRNAs are involved in mediating the host-IV interaction. Using miRNA microarrays, we identified several miRNAs aberrantly expressed in IV-infected human lung epithelial cells (A549). Specifically, miR-let-7c was highly up-regulated in IV-infected A549 cells. PITA and miRanda database screening indicated that the let-7c seed sequence is a perfect complementary sequence match to the 3' untranslated region (UTR) of viral gene M1 (+) cRNA, but not to PB2 and PA. As detected by a luciferase reporter system, let-7c directly targeted the 3'-UTR of M1 (+) cRNA, but not PB2 and PA. To experimentally identify the function of cellular let-7c, precursor let-7c was transfected into A549 cells. Let-7c down-regulated IV M1 expression at both the (+) cRNA and protein levels. Furthermore, transfection with a let-7c inhibitor enhanced the expression of M1. Therefore, let-7c may reduce IV replication by degrading M1 (+) cRNA. This is the first report indicating that cellular miRNA regulates IV replication through the degradation of viral gene (+) cRNA by matching the 3'-UTR of the viral cRNA. These findings suggest that let-7c plays a role in protecting host cells from the virus in addition to its known cellular functions.
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http://dx.doi.org/10.1111/j.1582-4934.2012.01572.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823446PMC
October 2012

[The effect of Aldosterone on the proliferation and collagen production of cardiac fibroblasts].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2011 Apr;27(4):386-8

Department of Cardiology, Chinese PLA General Hospital, Beijing 100853, China.

Aim: To investigate the effect of aldosterone (ALD) on the proliferation of fetal cardiac fibroblasts (FCFS) and the production of collagen I and collagen III in FCFS.

Methods: FCFS were isolated by collagenase II and purified with differential attachment and detachment method. The proliferation of FCFS after ALD administration was assessed by CCK-8. The mRNA expression of COL1A1 and COL3A1 were assessed by reverse transcription polymerase chain reaction (RT-PCR) and the protein production of COL1A1 and COL3A1 were assessed by Western blot.

Results: ALD facilitated the proliferation of FCFS concentration-dependently. ALD with lower concentration (10(-9);, 10(-8);, 10(-7); mol/L) significantly improved the expression of COL1A1 and COL3A1, while ALD with higher concentration of had no obvious effect.

Conclusion: ALD improved the proliferation of FCFS concentration-dependently. And in a certain concentration range, ALD improved the expression of COL1A1 and COL3A1 while higher concentration had opposite effect. There is no linear relationship among the effects of ALD on the proliferation of FCFS, expression and protein production of COL1A1 and COL3A1.
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April 2011

Analysis of synonymous codon usage bias in 09H1N1.

Virol Sin 2010 Oct 8;25(5):329-40. Epub 2010 Oct 8.

Beijing Institute of Radiation Medicine, Beijing, 100850, China.

A novel subtype of influenza A virus 09H1N1 has rapidly spread across the world. Evolutionary analyses of this virus have revealed that 09H1N1 is a triple reassortant of segments from swine, avian and human influenza viruses. In this study, we investigated factors shaping the codon usage bias of 09H1N1 and carried out cluster analysis of 60 strains of influenza A virus from different subtypes based on their codon usage bias. We discovered that more preferentially used codons of 09H1N1 are A-ended or U-ended, and the intra-genomic codon usage bias of 09H1N1 is quite low. Base composition constraint, dinucleotide biases and translational selection are the main factors influencing the codon usage bias of 09H1N1. At the genome level, we find that the codon usage bias of 09H1N1 is similar to H1N1 (A/swine/Kansas/77778/2007H1N1), H9N2 from Asia, H1N2 from Asia and North America and H3N2 from North America. Our results provide insight for understanding the processes governing evolution, regulation of gene expression, and revealing the evolution of 09H1N1.
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http://dx.doi.org/10.1007/s12250-010-3123-3DOI Listing
October 2010

[A genetic optimization designing method for microorganism detection genechip probe based on genetic algorithm].

Zhongguo Yi Liao Qi Xie Za Zhi 2008 Mar;32(2):89-92

Beijing Institute of Radiation Medicine, Military Medical Science College, Beijing.

A new automatic selection approach of microorganism specific fragment combination is presented in this paper. Genetic algorithm is used to search optimal solution on the basis of classification ability of SNP combination, which is evaluated by the rough set theory. Other related experimental parameters are also been incorporated. Experimental results show that the method can find the best SNP combination pattern efficiently and accurately, which implies that it is a reliable approach to the genechip probe design.
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March 2008

[Sequence analysis of the complete genome of bocavirus WLL-1].

Bing Du Xue Bao 2007 Jan;23(1):57-9

The First People's Hospital of Wenlin, Wenling 317500, China.

Human bocavirus, which was firstly discovered in 2005, is a new human parvovirus associated with lower respiratory tract infection in children. In this study, a human bocavirus, named WLL-1 isolate, was identified in Wenlin County, Zhejiang Province. The genome of bocavirus WLL-1 has been sequenced and analyzed. Phylogenetic analyses showed that WLL-1 shares 99% homology with other bocaviruses recently reported, but also has some special variations.
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January 2007

[Progress in a research on biochip image analysis].

Zhongguo Yi Liao Qi Xie Za Zhi 2007 Mar;31(2):108-11

Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing.

Microarray imaging is considered as an important tool for large scale analysis of gene expression. The accuracy of the gene expression depends on the experiment itself and further image processing. It's well known that the image analysis introduced during the experiment will greatly affect the accuracy of the gene expression. Microarray image analysis plays a potentially-arge impact on the gene detecting subsequent analysis (image segmentation, spot intensity and spot intensity extraction). In this paper, based on the characters of microarray images, the methods of microarray images' denoising and automatic-identification of the spot are reviewed.
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March 2007

Protocatechuic aldehyde inhibits hepatitis B virus replication both in vitro and in vivo.

Antiviral Res 2007 Apr 16;74(1):59-64. Epub 2007 Jan 16.

Beijing Institute of Radiation Medicine, Beijing 100850, PR China.

Natural compounds provide a large reservoir of potentially active anti-hepatitis B virus (HBV) agents. We examined the direct effects of protocatechuic aldehyde (PA; derived from the Chinese herb, Salvia miltiorrhiza) on HBV replication in HepG2 2.2.15 cell line and duck hepatitis B virus (DHBV) replication in ducklings in vivo. The extracellular HBV DNA, hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) concentrations in cell culture medium were determined by quantitative real-time PCR and ELISA, respectively. DHBV in duck serum was analyzed by dot blot. PA appeared to downregulate the secretion of HBsAg and HBeAg as well as the release of HBV DNA from HepG2 2.2.15 in a dose- and time-dependent manner at concentrations between 24 and 48 microg/mL. PA (25, 50, or 100 mg/kg, intraperitoneally, twice daily) also reduced viremia in DHBV-infected ducks. We provide the first evidence that PA, a novel anti-HBV substance derived from traditional Chinese herb S. miltiorrhiza, can efficiently inhibits HBV replication in HepG2 2.2.15 cell line in vitro and inhibit DHBV replication in ducks in vivo. PA therefore warrants further investigation as a potential therapeutic agent for HBV infections.
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http://dx.doi.org/10.1016/j.antiviral.2006.12.005DOI Listing
April 2007

[Screening and their anti-tumor activity of antisense oligodeoxynucleotides targeting KDR mRNA in breast cancer MCF-7 cells].

Zhonghua Zhong Liu Za Zhi 2006 Apr;28(4):248-52

Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China.

Objective: To screen the antisense oligodeoxynucleotides (asONs) which could hybridize with KDR (kinase insert domain-containing receptor) mRNA in an effective and specific way and to explore their anti-tumor effects on breast cancer MCF-7 cell line in vitro.

Methods: The asONs were firstly selected using oligodeoxynucleotides library hybridization or computer prediction, then their hybridization ability with KDR mRNA was further tested with oligonucleotide microarray. The asONs with strong hybridization intensity were selected. Their inhibitory effects on MCF-7 cells proliferation and KDR expression were assayed by MTT, RT-PCR and Western blotting assay, respectively.

Results: In 13 asONs selected with oligodeoxynucleotides library hybridization, 8 (8/13, 61.5%) showed strong hybridization signals, while such was only 1 in 17 asONs designed by computer prediction. 9 asONs with strong hybridization intensity were selected and synthesized with phosphorothioated modification. All these asONs inhibited the MCF-7 cells proliferation in a dose-dependent manner, in which asON4 and asON7 screened by oligodeoxynucleotides library in combination with oligonucleotide microarray were the most effective, with inhibitory rates of 51.6% and 62.2% at 0.8 micromol/L, respectively. The KDR expression at mRNA and protein levels was reduced by both the two asONs, in a dose-dependent manner.

Conclusion: asONs screened by oligodeoxynucleotides library hybridization are well consistent with that chosen with oligonucleotide microarray. The combination of oligodeoxynucleotides library with oligonucleotide microarray is an effective approach of asONs screening. The asONs targeting KDR mRNA showed prominent anti-tumor activity on breast cancer MCF-7 cells.
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April 2006

Effective siRNA targets screening for human telomerase reverse transcriptase.

World J Gastroenterol 2005 Apr;11(16):2497-501

Beijing Institute of Radiation Medicine, No. 27 Taiping Road, Beijing 100850, China.

Aim: To study the inhibitory effects of siRNAs targeting different hTERT sequences and to screen the effective siRNA sequence.

Methods: Five double-stranded siRNAs targeting coding and non-coding regions of hTERT gene were designed and synthesized by T7 transcription system in vitro. siRNA4 sequence was screened by full length gene targeting technique and the rest of the siRNA sequences were selected randomly. After being purified by ethanol precipitation, the siRNAs were transfected to the human hepatocellular carcinoma cell (HepG2) by Lipofectamine 2000. At 48-72 h after siRNAs transfection, MTT assay, RT-PCR and Western-blot were applied to evaluate the effects of siRNAs on cell growth, mRNA and protein expression level of hTERT gene, respectively.

Results: Compared to the control cells, the cells treated with the five double-stranded siRNAs exhibited different degrees of inhibition of cell proliferation in a dose-dependent manner. siRNA2 and siRNA4, exhibited obvious effects of inhibiting hTERT mRNA and protein expression in HepG2 cells.

Conclusion: siRNAs targeting different hTERT sequences have significantly various inhibitory effects on hTERT gene expression. The siRNA sequence screened by full length gene targeting technique has comparable inhibitory effect with the rest siRNA sequences screened by random selection, suggesting that siRNAs and antisense oligonucleic acids may have the same effective target sites. Compared with chemical synthesis method, synthesizing double-stranded siRNA by T7 transcription system in vitro is a rapid, simple, and inexpensive method suitable for screening high-effect siRNA targeting site for specific gene.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4305642PMC
http://dx.doi.org/10.3748/wjg.v11.i16.2497DOI Listing
April 2005

HBVPathDB: a database of HBV infection-related molecular interaction network.

World J Gastroenterol 2005 Mar;11(11):1690-2

Beijing Institute of Radiation Medicine, 27 Taiping Street, Haidian District, Beijing 100850, China.

Aim: To describe molecules or genes interaction between hepatitis B viruses (HBV) and host, for understanding how virus' and host's genes and molecules are networked to form a biological system and for perceiving mechanism of HBV infection.

Methods: The knowledge of HBV infection-related reactions was organized into various kinds of pathways with carefully drawn graphs in HBVPathDB. Pathway information is stored with relational database management system (DBMS), which is currently the most efficient way to manage large amounts of data and query is implemented with powerful Structured Query Language (SQL). The search engine is written using Personal Home Page (PHP) with SQL embedded and web retrieval interface is developed for searching with Hypertext Markup Language (HTML).

Results: We present the first version of HBVPathDB, which is a HBV infection-related molecular interaction network database composed of 306 pathways with 1 050 molecules involved. With carefully drawn graphs, pathway information stored in HBVPathDB can be browsed in an intuitive way. We develop an easy-to-use interface for flexible accesses to the details of database. Convenient software is implemented to query and browse the pathway information of HBVPathDB. Four search page layout options-category search, gene search, description search, unitized search-are supported by the search engine of the database. The database is freely available at http://www.bio-inf.net/HBVPathDB/HBV/.

Conclusion: The conventional perspective HBVPathDB have already contained a considerable amount of pathway information with HBV infection related, which is suitable for in-depth analysis of molecular interaction network of virus and host. HBVPathDB integrates pathway data-sets with convenient software for query, browsing, visualization, that provides users more opportunity to identify regulatory key molecules as potential drug targets and to explore the possible mechanism of HBV infection based on gene expression datasets.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4305955PMC
http://dx.doi.org/10.3748/wjg.v11.i11.1690DOI Listing
March 2005

Screening of specific antigens for SARS clinical diagnosis using a protein microarray.

Analyst 2005 Apr 14;130(4):474-82. Epub 2005 Feb 14.

Beijing Institute of Radiation Medicine, Beijing, 100850, People's Republic of China.

In this study several SARS-CoV structural proteins and fragments were expressed in E. coli as GST or TRX fusion proteins. They were fabricated on a microarray and tested with sera from SARS patients. Antigenic screening indicated that recombinant GST-N2 fusion protein, the carboxy-terminus 213aa-423aa of N protein, was strongest positive and weakest non-specific compared with others. An indirect antibody ELISA method was developed and clinical positive and negative sera for their antibodies against GST-N2 fusion protein were assayed. 311 out of the 442 sera from clinical SARS inpatients, as well as 229 out of 302 sera from convalescent patients gave positive reactivities; positive rates were 70.4% and 75.8% respectively. Sera from a total of 2726 non-SARS patients and healthy individuals were tested and the false positive rate was only 0.07%. When the sensitivity control sample was diluted 1 : 64, it yielded OD values above the cutoff value. Reported data showed that this was a relatively high degree of sensitivity and specificity for SARS-CoV antibody testing. The data indicate that GST-N2 fusion protein, which was screened by protein microarray, may be a valuable diagnostic antigen for the development of serological assays for SARS. In addition, protein microarray assay presents a higher positive rate and sensitivity (86.1% and 1 : 200) compared with the traditional ELISA screening method, and could provide a rapid, parallel and high-throughput antigen screening platform.
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http://dx.doi.org/10.1039/b415888aDOI Listing
April 2005