Xian-Qiang Mi

3 ' UTR shortening identifies high-risk cancers with targeted dysregulation of the ceRNA network

Competing endogenous RNA (ceRNA) interactions form a multilayered network that regulates gene expression in various biological pathways. Recent studies have demonstrated novel roles of ceRNA interactions in tumorigenesis, but the dynamics of the ceRNA network in cancer remain unexplored. Here, we examine ceRNA network dynamics in prostate cancer from the perspective of alternative cleavage and polyadenylation (APA) and reveal the principles of such changes. Analysis of exon array data revealed that both shortened and lengthened 3′UTRs are abundant. Consensus clustering with APA data stratified cancers into groups with differing risks of biochemical relapse and revealed that a ceRNA subnetwork enriched with cancer genes was specifically dysregulated in high-risk cancers. The novel connection between 3′UTR shortening and ceRNA network dysregulation was supported by the unusually high number of microRNA response elements (MREs) shared by the dysregulated ceRNA interactions and the significantly altered 3′UTRs. The dysregulation followed a fundamental principle in that ceRNA interactions connecting genes that show opposite trends in expression change are preferentially dysregulated. This targeted dysregulation is responsible for the majority of the observed expression changes in genes with significant ceRNA dysregulation and represents a novel mechanism underlying aberrant oncogenic expression.

Synthesis, structure, and conformation of terphenylene-derived azacalix[4]aromatics

Abstract Several novel azacalix[4]aromatics constituting terphenylene units have been synthesized via sequential nucleophilic aromatic substitution reactions of 5′-t-butyl-(1,1′:3′,1″-terphenyl)-3,3″-diamine 9 and 5′-t-butyl-(1,1′:3′,1″-terphenyl)– 4,4″-diamine 11 with 1,5-difluoro-2,4-dinitrobenzene and cyanuric chloride, respectively. The bridging –NH– functions of the tetra-nitro substituted azacalix[2]arene[2]terphenylenes 1 and 2 have been transformed to the corresponding –N(CH3)– bridged azacalix[2]arene[2]terphenylenes 3 and 4 via N-alkylation. Single crystal X-ray analysis revealed that the terphenyl-3,3″-diamine derived azacalix[2]terphenylene[2]triazine 5 adopts a distorted chair conformation in the solid state, and the terphenyl-4,4″-diamine derived azacalix[2]terphenylene[2]triazine 6 was found to adopt a 1,3-alternate conformation.

Efficient one-pot synthesis of peapod-like hollow carbon nanomaterials for utrahigh drug loading capacity

In this paper, peapod-like hollow carbon nanomaterial was fabricated via an efficient one-pot hydrothermal route. The carbon-silica composite was employed as the precursor and cetyltrimethylammonium bromide (CTAB) as the morphology-controlled agent. SEM and TEM results indicated that the carbon shell and the silica core in the precursor were not closely linked but rattle-type structure. After removing the silica template, the obtained carbon product had uniform peapod-like morphology, interconnected pores and high specific surface areas (above 800.0 m(2)/g). We found that CTAB played an important role in the formation of the products with peapod-like morphology. The particle sizes of the hollow carbon nanospheres were readily adjusted by varying the dosage of tetraethoxysilane (TEOS) and the volume ratio of ethanol and water. Based on the experimental results, the formation mechanism of the hollow carbon nanomaterial was also discussed. By virtue of their unique nanostructure and porous properties, the peapod-like hollow carbon nanomaterial exhibited ultrahigh drug loading capacity above 98.4% for doxorubicin hydrochloride (DOX).

Carboxylic Acid-Derived Oxacalix[2]arene[2]pyrazine Self-Assembles into Unprecedented Diamondoid Networks

A 1,3-alternate conformational oxacalix[2]arene[2]pyrazine, 1, made up of two tetrahedrally oriented –COOH functions and two upper rim pyrazinyl nitrogen atoms, self-assembles into an unprecedented six-fold interpenetrated diamondoid network via intermolecular hydrogen bond interactions. Disordered guest molecules could be included in the hydrophobic channels presented in the supramolecular aggregates.

Trigonal prismatic bicyclocalixaromatics, synthesis and structures

Two trigonal prismatic bicyclooxacalixarenes 1 and 2 were obtained by condensation reaction of 1,3,5-tri(p-hydroxyphenyl)benzene and 2,4,6-tri(p-hydroxyphenyl)triazine, respectively, with 1,5-difluoro-2,4-dinitrobenzene. Single crystal structural analysis revealed that the bicyclooxacalixarene 1 adopts a distorted triangular prismatic structure. Bicyclooxacalixarene 2, however, possesses an almost D 3 h symmetric triangular prismatic structure. The colorimetric changes in the acetone solutions of 1 or 2 upon addition of certain anions have been found highly relevant to the nitro-substituents in the phenyl pillars, not to their macrocyclic structures.

An electrochemical immunosensor for quantitative detection of ficolin-3.

Diabetes mellitus (DM) is one of the most common metabolic disorders in the world, of which more than 90% is type-2 diabetes mellitus (T2DM). There is a rather urgent need for reliable, sensitive and quick detection techniques in clinical application of T2DM. Ficolin-3 is a potential biomarker of T2DM, because serum ficolin-3 levels are associated with insulin resistance and predict the incidence of T2DM. Herein, a sandwich-type electrochemical immunosensor was developed for the detection of ficolin-3 in human serum. Cyclic voltammetry and the amperometric current versus time were used to characterize the performance of the immunosensor. Under optimal conditions, the detection limitation of ficolin-3 was 100 ng ml(-1) and the linear dynamic range was between 2 and 50 μg ml(-1). The method has ideal accuracy, excellent stability and selectivity and has wide application prospects in clinical research.

Photobiomodulation on KATP Channels of Kir6.2-Transfected HEK-293 Cells

Background and Objective. ATP-sensitive potassium (KATP) channel couples cell metabolism to excitability. To explore role of KATP channels in cellular photobiomodulation, we designed experiment to study effect of low intensity 808 nm laser irradiation on the activity of membrane KATP channel. Study Design/Materials and Methods. Plasmids encoding Kir6.2 was constructed and heterologously expressed in cultured mammalian HEK-293 cells. The patch-clamp and data acquisition systems were used to record KATP channel current before and after irradiation. A laser beam of Ga-As 808 nm at 5 mW/cm2 was used in experiments. A one-way ANOVA test followed by a post hoc Student-Newman-Keuls test was used to assess the statistical differences between data groups. Results. Obvious openings of KATP channels of Kir6.2-transfected HEK-293 cells and excised patches were recorded during and after low intensity 808 nm laser irradiation. Compared with the channels that did not undergo irradiation, open probability, current amplitude, and dwell time of KATP channels after irradiation improved. Conclusions. Low intensity 808 nm laser irradiation may activate membrane KATP channels of Kir6.2-transfected HEK-293 cells and in excised patches.