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author:("Zhang, wensu")
1.  Branched Peptide Boronic Acids (BPBAs): A Novel Mode of Binding Towards RNA 
We report branched peptide boronic acids (BPBAs) that bind to RRE IIB from an on-bead high-throughput screening of a 3.3.4-library (46,656 compounds). We demonstrate that boronic acids are tunable moieties that afford a novel binding mode towards RNA.
PMCID: PMC3601739  PMID: 23412370
2.  Evaluation about the Performance of E-Government Based on Interval-Valued Intuitionistic Fuzzy Set 
The Scientific World Journal  2014;2014:234241.
The evaluation is an important approach to promote the development of the E-Government. Since the rapid development of E-Government in the world, the E-Government performance evaluation has become a hot issue in the academia. In this paper, we develop a new evaluation method for the development of the E-Government based on the interval-valued intuitionistic fuzzy set which is a powerful technique in expressing the uncertainty of the real situation. First, we extend the geometric Heronian mean (GHM) operator to interval-valued intuitionistic fuzzy environment and proposed the interval-valued intuitionistic fuzzy GHM (IIFGHM) operator. Then, we investigate the relationships between the IIFGHM operator and some existing ones, such as generalized interval-valued intuitionistic fuzzy HM (GIIFHM) and interval-valued intuitionistic fuzzy weighted Bonferoni mean operator. Furthermore, we validate the effectiveness of the proposed method using a real case about the E-Government evaluation in Hangzhou City, China.
PMCID: PMC3953636
3.  A New Method for E-Government Procurement Using Collaborative Filtering and Bayesian Approach 
The Scientific World Journal  2013;2013:129123.
Nowadays, as the Internet services increase faster than ever before, government systems are reinvented as E-government services. Therefore, government procurement sectors have to face challenges brought by the explosion of service information. This paper presents a novel method for E-government procurement (eGP) to search for the optimal procurement scheme (OPS). Item-based collaborative filtering and Bayesian approach are used to evaluate and select the candidate services to get the top-M recommendations such that the involved computation load can be alleviated. A trapezoidal fuzzy number similarity algorithm is applied to support the item-based collaborative filtering and Bayesian approach, since some of the services' attributes can be hardly expressed as certain and static values but only be easily represented as fuzzy values. A prototype system is built and validated with an illustrative example from eGP to confirm the feasibility of our approach.
PMCID: PMC3872429  PMID: 24385869
4.  An Intronic miRNA Regulates Expression of the Human Endothelial Nitric Oxide Synthase Gene and Proliferation of Endothelial Cells by a Mechanism Related to the Transcription Factor SP-1 
PLoS ONE  2013;8(8):e70658.
This study was to investigate the molecular mechanisms underlying the 27nt-miRNA-mediated regulation of expression of the endothelial nitric oxide synthase (eNOS) gene.
Cell lines overexpressing 27nt-miRNA or its mutant were established by transfecting the miRNA expression vector into the endothelial cells. eNOS mRNA and protein expression were examined by RT-PCR and Western Blotting, respectively. Luciferase activity reporter system was used to study the target of 27nt-miRNA.
The results showed that overexpression of 27nt-miRNA significantly inhibited eNOS mRNA level and protein expression, and reduced the eNOS transcriptional efficiency. Such inhibitory effects of 27nt-miRNA were attenuated by the sequence mutations in 27nt-miRNA. Interestingly, the transcription factor SP-1 expression was reduced by 27nt-miRNA. Meanwhile, overxpression of SP-1 protein partially restored eNOS expression, and rescued the 27nt-miRNA-mediated reduction of endothelial cell proliferation. Moreover, certain sites in the SP-1 mRNA were found to be the direct target of 27nt-miRNA by a luciferase reporter system.
These results demonstrate that the 27nt-miRNA suppresses eNOS gene expression and SP-1 expression in vascular endothelial cells. The 27nt-miRNA directly target to SP-1 mRNA, thereby contributing to proliferation of endothelial cells.
PMCID: PMC3734264  PMID: 23940615
5.  Subcongenic analyses reveal complex interactions between distal Chromosome 4 genes controlling diabetogenic B cells and CD4 T cells in NOD mice.1 
Autoimmune Type 1 Diabetes (T1D) in humans and NOD mice results from interactions between multiple susceptibility genes (termed Idd) located within and outside the MHC. Despite sharing ~88% of their genome with NOD, including the H2g7 MHC haplotype and other important Idd genes, the closely related NOR strain fails to develop T1D due to resistance alleles in residual genomic regions derived from C57BLKS mice mapping to Chromosomes (Chr.) 1, 2 and 4. We previously produced an NOD background strain developing a greatly decreased T1D incidence due to a NOR-derived 44.31 Mb congenic region on distal Chr. 4 containing disease resistance alleles decreasing the pathogenic activity of autoreactive B and CD4 T cells. In this study a series of subcongenic strains for the NOR-derived Chr. 4 region were utilized to significantly refine genetic loci regulating diabetogenic B and CD4 T cell activity. Analyses of these subcongenic strains revealed the presence of at least two NOR origin T1D resistance genes within this region. A 6.22Mb region between rs13477999 and D4Mit32, not previously known to contain a locus affecting T1D susceptibility and now designated Idd25, was found to contain the main NOR gene(s) dampening diabetogenic B cell activity, with Ephb2 and/or Padi2 being strong candidates as the causal variants. Penetrance of this Idd25 effect was influenced by genes in surrounding regions controlling B cell responsiveness and anergy induction. Conversely, the gene(s) controlling pathogenic CD4 T cell activity was mapped to a more proximal 24.26Mb region between the rs3674285 and D4Mit203 markers.
PMCID: PMC3401322  PMID: 22732593
Rodent; B cells; T cells; Diabetes; Gene Regulation
6.  Clear cell renal cell carcinoma associated microRNA expression signatures identified by an integrated bioinformatics analysis 
Clear cell renal cell carcinoma (ccRCC) represents the most invasive and common adult kidney neoplasm. Mounting evidence suggests that microRNAs (miRNAs) are important regulators of gene expression. But their function in tumourigenesis in this tumour type remains elusive. With the development of high throughput technologies such as microarrays and NGS, aberrant miRNA expression has been widely observed in ccRCC. Systematic and integrative analysis of multiple microRNA expression datasets may reveal potential mechanisms by which microRNAs contribute to ccRCC pathogenesis.
We collected 5 public microRNA expression datasets in ccRCC versus non-matching normal renal tissues from GEO database and published literatures. We analyzed these data sets with an integrated bioinformatics framework to identify expression signatures. The framework incorporates a novel statistic method for abnormal gene expression detection and an in-house developed predictor to assess the regulatory activity of microRNAs. We then mapped target genes of DE-miRNAs to different databases, such as GO, KEGG, GeneGo etc, for functional enrichment analysis.
Using this framework we identified a consistent panel of eleven deregulated miRNAs shared by five independent datasets that can distinguish normal kidney tissues from ccRCC. After comparison with 3 RNA-seq based microRNA profiling studies, we found that our data correlated well with the results of next generation sequencing. We also discovered 14 novel molecular pathways that are likely to play a role in the tumourigenesis of ccRCC.
The integrative framework described in this paper greatly improves the inter-dataset consistency of microRNA expression signatures. Consensus expression profile should be identified at pathway or network level to address the heterogeneity of cancer. The DE-miRNA signature and novel pathways identified herein could provide potential biomarkers for ccRCC that await further validation.
PMCID: PMC3740788  PMID: 23841900
Meta-analysis; Network biomarker; MicroRNA; Clear cell renal cell carcinoma; Pathway analysis; Heterogeneity
7.  Towards Targeting RNA Structure: Branched Peptides as Cell Permeable Ligands to TAR RNA 
ACS Chemical Biology  2011;7(1):210-217.
Rational design of RNA ligands continues to be a formidable challenge, but the potential powerful applications in biology and medicine catapults it to the forefront of chemical research. Indeed, small molecule and macromolecular intervention are attractive approaches but selectivity and cell permeability can be a hurdle. An alternative strategy is to use molecules of intermediate molecular weight that possess large enough surface area to maximize interaction with the RNA structure but are small enough to be cell permeable. Herein, we report the discovery of non-toxic and cell permeable branched peptide (BP) ligands that bind to TAR RNA in the low micromolar range from on-bead high throughput screening of 4,096 compounds. TAR is a short RNA motif in the 5′-UTR of HIV-1 that is responsible for efficient generation of full RNA transcripts. We demonstrate that BPs are selective for the native TAR RNA structure and that "branching" in peptides provides multivalent interaction, which increases binding affinity to RNA.
PMCID: PMC3262918  PMID: 22003984
8.  Identification of an AAA ATPase VPS4B-Dependent Pathway That Modulates Epidermal Growth Factor Receptor Abundance and Signaling during Hypoxia 
Molecular and Cellular Biology  2012;32(6):1124-1138.
VPS4B, an AAA ATPase (ATPase associated with various cellular activities), participates in vesicular trafficking and autophagosome maturation in mammalian cells. In solid tumors, hypoxia is a common feature and an indicator of poor treatment outcome. Our studies demonstrate that exogenous or endogenous (assessed with anchorage-independent three-dimensional multicellular spheroid culture) hypoxia induces VPS4B downregulation by the ubiquitin-proteasome system. Inhibition of VPS4B function by short hairpin VPS4B (sh-VPS4B) or expression of dominant negative VPS4B(E235Q) promotes anchorage-independent breast cancer cell growth and resistance to gefitinib, U0126, and genotoxicity. Biochemically, hyperactivation of epidermal growth factor receptor (EGFR), a receptor tyrosine kinase essential for cell proliferation and survival, accompanied by increased EGFR accumulation and altered intracellular compartmentalization, is observed in cells with compromised VPS4B. Furthermore, enhanced FOS/JUN induction and AP-1 promoter activation are noted in EGF-treated cells with VPS4B knockdown. However, VPS4B depletion does not affect EGFRvIII stability or its associated signaling. An inverse correlation between VPS4B expression and EGFR abundance is observed in breast tumors, and high-grade or recurrent breast carcinomas exhibit lower VPS4B expression. Together, our findings highlight a potentially critical role of VPS4B downregulation or chronic-hypoxia-induced VPS4B degradation in promoting tumor progression, unveiling a nongenomic mechanism for EGFR overproduction in human breast cancer.
PMCID: PMC3295017  PMID: 22252323
9.  A facile approach to nanoarchitectured three-dimensional graphene-based Li–Mn–O composite as high-power cathodes for Li-ion batteries 
We report a facile method to prepare a nanoarchitectured lithium manganate/graphene (LMO/G) hybrid as a positive electrode for Li-ion batteries. The Mn2O3/graphene hybrid is synthesized by exfoliation of graphene sheets and deposition of Mn2O3 in a one-step electrochemical process, which is followed by lithiation in a molten salt reaction. There are several advantages of using the LMO/G as cathodes in Li-ion batteries: (1) the LMO/G electrode shows high specific capacities at high gravimetric current densities with excellent cycling stability, e.g., 84 mAh·g−1 during the 500th cycle at a discharge current density of 5625 mA·g−1 (~38.01 C capacity rating) in the voltage window of 3–4.5 V; (2) the LMO/G hybrid can buffer the Jahn–Teller effect, which depicts excellent Li storage properties at high current densities within a wider voltage window of 2–4.5 V, e.g., 93 mAh·g−1 during the 300th cycle at a discharge current density of 5625 mA·g−1 (~38.01 C). The wider operation voltage window can lead to increased theoretical capacity, e.g., 148 mAh·g−1 between 3 and 4.5 V and 296 mAh·g−1 between 2 and 4.5 V; (3) more importantly, it is found that the attachment of LMO onto graphene can help to reduce the dissolution of Mn2+ into the electrolyte, as indicated by the inductively coupled plasma (ICP) measurements, and which is mainly attributed to the large specific surface area of the graphene sheets.
PMCID: PMC3458596  PMID: 23019546
cathode; graphene; Li-ion battery; lithium manganate
10.  Facile Analysis and Sequencing of Linear and Branched Peptide Boronic Acids by MALDI Mass Spectrometry 
Analytical chemistry  2011;83(9):3548-3554.
Interest in peptides incorporating boronic acid moieties is increasing due to their potential as therapeutics/diagnostics for a variety of diseases such as cancer. The utility of peptide boronic acids may be expanded with access to vast libraries that can be deconvoluted rapidly and economically. Unfortunately, current detection protocols using mass spectrometry are laborious and confounded by boronic acid trimerization, which requires time consuming analysis of dehydration products. These issues are exacerbated when the peptide sequence is unknown, as with de novo sequencing, and especially when multiple boronic acid moieties are present. Thus, a rapid, reliable and simple method for peptide identification is of utmost importance. Herein, we report the identification and sequencing of linear and branched peptide boronic acids containing up to five boronic acid groups by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Protocols for preparation of pinacol boronic esters were adapted for efficient MALDI analysis of peptides. Additionally, a novel peptide boronic acid detection strategy was developed in which 2,5-dihydroxybenzoic acid (DHB) served as both matrix and derivatizing agent in a convenient, in situ, on-plate esterification. Finally, we demonstrate that DHB-modified peptide boronic acids from a single bead can be analyzed by MALDI-MSMS analysis, validating our approach for the identification and sequencing of branched peptide boronic acid libraries.
PMCID: PMC3090651  PMID: 21449540
MALDI-MS; peptide sequencing; matrix; deconvolution; high throughput screen
11.  A Practical Comparison of De Novo Genome Assembly Software Tools for Next-Generation Sequencing Technologies 
PLoS ONE  2011;6(3):e17915.
The advent of next-generation sequencing technologies is accompanied with the development of many whole-genome sequence assembly methods and software, especially for de novo fragment assembly. Due to the poor knowledge about the applicability and performance of these software tools, choosing a befitting assembler becomes a tough task. Here, we provide the information of adaptivity for each program, then above all, compare the performance of eight distinct tools against eight groups of simulated datasets from Solexa sequencing platform. Considering the computational time, maximum random access memory (RAM) occupancy, assembly accuracy and integrity, our study indicate that string-based assemblers, overlap-layout-consensus (OLC) assemblers are well-suited for very short reads and longer reads of small genomes respectively. For large datasets of more than hundred millions of short reads, De Bruijn graph-based assemblers would be more appropriate. In terms of software implementation, string-based assemblers are superior to graph-based ones, of which SOAPdenovo is complex for the creation of configuration file. Our comparison study will assist researchers in selecting a well-suited assembler and offer essential information for the improvement of existing assemblers or the developing of novel assemblers.
PMCID: PMC3056720  PMID: 21423806

Results 1-11 (11)