Circular RNA (circRNA) is a group of RNA family generated by RNA circularization, which was discovered ubiquitously across different species and tissues. However, there is no global view of tissue specificity for circRNAs to date. Here we performed the comprehensive analysis to characterize the features of human and mouse tissue-specific (TS) circRNAs. We identified in total 302 853 TS circRNAs in the human and mouse genome, and showed that the brain has the highest abundance of TS circRNAs. We further confirmed the existence of circRNAs by reverse transcription polymerase chain reaction (RT-PCR). We also characterized the genomic location and conservation of these TS circRNAs and showed that the majority of TS circRNAs are generated from exonic regions. To further understand the potential functions of TS circRNAs, we identified microRNAs and RNA binding protein, which might bind to TS circRNAs. This process suggested their involvement in development and organ differentiation. Finally, we constructed an integrated database TSCD (Tissue-Specific CircRNA Database: http://gb.whu.edu.cn/TSCD) to deposit the features of TS circRNAs. This study is the first comprehensive view of TS circRNAs in human and mouse, which shed light on circRNA functions in organ development and disorders.

Long Stokes shift dyes that minimize cross-talk between the excitation source and fluorescent emission to improve the signal-to-background ratio are highly desired for fluorescence imaging. However, simple small molecular dyes with large Stokes shift (more than 120 nanometers) and near-infrared (NIR) emissions have been rarely reported so far. Here, inspired by the chromophore chemical structure of fluorescent proteins, we designed and synthesized a series of styrene oxazolone dyes (SODs) with simple synthetic methods, which show NIR emissions (>650 nanometers) with long Stokes shift (ranged from 136 to 198 nanometers) and small molecular weight (<450 daltons). The most promising SOD9 shows rapid renal excretion and blood-brain barrier passing properties. After functioning with the mitochondrial-targeted triphenylphosphonium (TPP) group, the resulting SOD9-TPP can be engineered for head-neck tumor imaging, fluorescence image–guided surgery, brain neuroimaging, and on-site pathologic analysis. In summary, our findings add an essential small molecular dye category to the classical dyes.

The reaction mechanisms for the MTO-catalyzed deoxygenation of epoxides and diols were investigated with the aid of density functional theory (DFT) calculations. The DFT results indicate that the reaction starts with a [2σ+2π] addition of epoxide to MTO to give a five-membered-ring rhena-2,5-dioxolane intermediate, followed by H2 addition, proton transfer, and extrusion of olefin to regenerate the catalyst. The experimental observation for formation and subsequent disappearance of diol appearing in the catalytic reaction is explained as follows. Diol was produced by the hydrolysis of epoxide with the coproduct water through the five-membered-ring rhena-2,5-dioxolane intermediate. Then the diol produced undergoes catalytic conversion to olefin by reacting with H2 under the catalytic conditions.

In this study, Cp*Co(iii)-catalyzed site-selective amidation of pyridones and isoquinolones using oxazolones as the amidation reagent is reported.

Tumor-targeted and stimuli-activatable nanosensitizers are highly desirable for cancer theranostics. However, designing smart nanosensitizers with multiple imaging signals and synergistic therapeutic activities switched on is challenging. Herein, we report tumortargeted and redox-activatable nanosensitizers (1-NPs) for sono-photodynamic immunotherapy of tumors by molecular co-assembly and redox-controlled disassembly. 1-NPs show a high longitudinal relaxivity (r 1 = 18.7 � 0.3 mM À 1 s À 1 ), but "off" dual fluorescence (FL) emission (at 547 and 672 nm), "off" sono-photodynamic therapy and indoleamine 2,3-dioxygenase 1 (IDO1) inhibition activities. Upon reduction by glutathione (GSH), 1-NPs rapidly disassemble and remotely release small molecules 2-Gd, Zn-PPA-SH and NLG919, concurrently switching on (1) dual FL emission, (2) sonophotodynamic therapy and (3) IDO1 inhibition activities. After systemic injection, 1-NPs are effective for bimodal FL and magnetic resonance (MR) imagingguided sono-photodynamic immunotherapy of orthotropic breast and brain tumors in mice under combined ultrasound (US) and 671-nm laser irradiation.

Abstract. The antitumor effects of ginsenoside Rg3 have been reported in several kinds of human malignant tumors. The purpose of this study was to investigate whether ginsenoside Rg3 can inhibit the growth of human hepatocellular carcinoma cell lines and to discuss the possible molecular mechanism(s). We cultured the human hepatocellular carcinoma cell lines, SMMC-7721 and HepG2. The cells were treated with different concentrations of ginsenoside Rg3 (0, 25, 50, 75 and 100 µg/ ml), and the cell proliferation was detected by MTT assay at the 12, 24, 36 and 48 h time-points. Flow cytometry experiments were carried out to investigate the effect of Rg3 on cell apoptosis after the cells had been treated with Rg3 (50 and 100 µg/ml) for 24 and 48 h. The expression levels of caspase-3, bax and bcl-2 in Rg3-treated cells (100 µg/ml, 48 h), as well as normal cells were detected through real-time PCR experiments. MTT assay showed that the inhibition rate of cell proliferation in the Rg3 groups was significantly higher compared to the control groups in both the SMMC-7721 and HepG2 cell lines, and the inhibition rate increased with increasing Rg3 concentrations and duration of treatment. Flow cytometry analysis demonstrated that the Rg3 groups had a significantly higher cell apoptotic rate compared to the control groups in both the SMMC-7721 and HepG2 cell lines, and that the effect of Rg3 on cell apoptosis occurred in a concentration-and time-dependent manner, as was also shown by the MTT assay. Real-time PCR analysis showed that the gene expression levels of caspase-3 and bax were significantly enhanced in the Rg3 groups compared to the control groups in both the SMMC-7721 and HepG2 cell lines, but the gene expression level of bcl-2 was significantly inhibited. These results indicate that ginsenoside Rg3 can effectively inhibit the growth of human hepatocellular carcinoma cell lines by inhibiting cancer cell proliferation and promoting cancer cell apoptosis, and it may promote cancer cell apoptosis via the endogenous mitochondrial-mediated caspase-dependent apoptotic pathway.

A simple and sensitive method for evaluating the chemical compositions of protein amino acids, including cystine (Cys)(2) and tryptophane (Try) has been developed, based on the use of a sensitive labeling reagent 2-(11H-benzo[alpha]-carbazol-11-yl) ethyl chloroformate (BCEC-Cl) along with fluorescence detection. The chromophore of the 1,2-benzo-3,4-dihydrocarbazole-ethyl chloroformate (BCEOC-Cl) molecule was replaced with the 2-(11H-benzo[alpha]-carbazol-11-yl) ethyl functional group, yielding the sensitive fluorescence molecule BCEC-Cl. The new reagent BCEC-Cl could then be substituted for labeling reagents commonly used in amino acid derivatization. The BCEC-amino acid derivatives exhibited very high detection sensitivities, particularly in the cases of (Cys)(2) and Try, which cannot be determined using traditional labeling reagents such as 9-fluorenyl methylchloroformate (FMOC-Cl) and ortho-phthaldialdehyde (OPA). The fluorescence detection intensities for the BCEC derivatives were compared to those obtained when using FMOC-Cl and BCEOC-Cl as labeling reagents. The ratios I (BCEC)/I (BCEOC) = 1.17-3.57, I (BCEC)/I (FMOC) = 1.13-8.21, and UV(BCEC)/UV(BCEOC) = 1.67-4.90 (where I is the fluorescence intensity and UV is the ultraviolet absorbance). Derivative separation was optimized on a Hypersil BDS C(18) column. The detection limits calculated from 1.0 pmol injections, at a signal-to-noise ratio of 3, ranged from 7.2 fmol for Try to 8.4 fmol for (Cys)(2). Excellent linear responses were observed, with coefficients of >0.9994. When coupled with high-performance liquid chromatography, the method established here allowed the development of a highly sensitive and specific method for the quantitative analysis of trace levels of amino acids including (Cys)(2) and Try from bee-collected pollen (bee pollen) samples.

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