An explorative study for leveraging transcriptomic data of embryonic stem cells in mining cancer stemness genes, regulators, and networks.

Due to the exquisite ability of cancer stemness to facilitate tumor initiation, metastasis, and cancer therapy resistance, targeting cancer stemness is expected to have clinical implications for cancer treatment. Genes are fundamental for forming and maintaining stemness. Considering shared genetic programs and pathways between embryonic stem cells and cancer stem cells, we conducted a study analyzing transcriptomic data of embryonic stem cells for mining potential cancer stemness genes. Firstly, we integrated co-expression and regression models and predicted 820 stemness genes. Results of gene enrichment analysis confirmed the good prediction performance for enriched signatures in cancer stem cells. Secondly, we provided an application case using the predicted stemness genes to construct a breast cancer stemness network. Mining on the network identified CD44, SOX2, TWIST1, and DLG4 as potential regulators of breast cancer stemness. Thirdly, using the signature of 31,028 chemical perturbations and their correlation with stemness marker genes, we predicted 67 stemness inhibitors with reasonable accuracy of 78%. Two drugs, namely Rigosertib and Proscillaridin A, were first identified as potential stemness inhibitors for melanoma and colon cancer, respectively. Overall, mining embryonic stem cell data provides a valuable way to identify cancer stemness regulators.

Novel Nanocrystal Injection of Insoluble Drug Anlotinib and Its Antitumor Effects on Hepatocellular Carcinoma.

The molecularly targeted agent anlotinib offers a novel therapeutic strategy against advanced hepatocellular carcinoma (HCC). With this study, we aimed to solve the technical problem of anlotinib being insoluble in injectable solutions; we also aimed to assess the antitumor activity of anlotinib on hepatocellular carcinoma cells. We prepared an anlotinib nanocrystal injection by wet grinding, and we optimized the prescription process using a transmission electron microscope (TEM) and a laser particle size analyzer (LPSA). The release of anlotinib from the injected nanocrystals was evaluated using LC-MS/MS in vitro, and the drug's anti-tumor effects were assessed in a nude mice tumor model. The anlotinib nanocrystals had a uniform particle size distribution (the average nanoparticle size was ~200 nm). The preparation of anlotinib into nanocrystals did not change the original crystal structure. The intravenous injection of anlotinib nanocrystals achieved anti-tumor activity at very low doses compared to those required for oral administration of an anlotinib suspension: anlotinib nanocrystals at a dose of 50 µg/kg inhibited the subcutaneous growth of the HCC cell line MHCC97-H; whereas the dose of anlotinib suspension required for an equivalent effect was 1 mg/kg. Therefore, our novel anlotinib nanocrystal injection preparation provides an option for achieving a safe and effective molecularly targeted therapy against advanced HCC.

A highly sensitive and selective on-off fluorescent sensor based on a complex of polySchiff-Fe2+ for Cr(vi) detection in an aqueous medium.

Designing exceptional probes to detect minute quantities of chromium(vi) is of huge importance for the safety and health of the human race. In this study, a green fluorescence emission probe (polyethylene Schiff base-chelated Fe2+ complex) was synthesized by a one-pot synthesis method for the highly selective and sensitive detection of Cr(vi) in an aqueous solution. The complex of polyethylene Schiff-Fe2+ was fully characterized, and it displayed satisfactory stability in the aqueous solution. The fluorescence emission could be quenched specifically by the introduction of Cr(vi) via the oxidation of the Fe2+-centered polyethylene Schiff base complex. The fluorescence intensity decreases linearly with the concentration of Cr(vi), and the corresponding detection limit was calculated to be 0.18 µM. Thus, the obtained fluorescence detection system could be used for Cr(vi) detection in tap water. These features provide potential uses of the as-prepared polyethylene Schiff-Fe2+ complex as a sensor for environmental applications.

Potential chiral fluorescent molecular probes based on an α,ß-unsaturated ketone for anion detection.

A series of potential chiral compounds containing an α,ß-unsaturated ketone was developed for anion detection. The interplay of compounds and biological momentous anions (Cl-, H2PO4-, I-, AcO-, HS-, F-, and Br-) was evaluated by UV-vis experiments, fluorescence experiments, and electrochemical tests. By comparison, compound 1 had the best selectivity and compound 5 had the strongest binding ability among the five compounds. And compound 5 had the highest sensitivity to H2PO4- among the measured anions, and it also can be applied to actual samples, the content of H2PO4- tested in the potassium dihydrogen phosphate fertilizer solution reached above 97.5% of the marked content, and the recovery rates were within the range of 98.5-99.1%, attesting that this method was reliable for the test of H2PO4- in fertilizer. Through HRMS titration, circular dichroism and optical rotation experiments, the probable interacted mechanism was proved that the interaction site was the C=C of the α,ß-unsaturated ketone structure. In addition, the interacted mechanism was researched from the perspective of chirality. Furthermore, theoretical investigation analysis was introduced to reveal that the roles of molecular frontier orbitals in molecular interplay were determined. Therefore, this series of potential chiral compounds has potential application prospects in anion recognition.

The synthesis, crystal, hydrogen sulfide detection and cell assement of novel chemsensors based on coumarin derivatives.

A series of chemsensors (1-4) containing fluorobenzene group based on coumarin derivatives have been developed for the selective and sensitive detection of H2S. The advantages of the synthesized fluorescent probe (compound 1) were the low detection limit (4 × 10-6 mol·L-1), good selectivity and high sensitivity which had been demonstrated through UV-vis, fluorescent titration experiments. Besides cytotoxicity test of compounds (1 and 2) was studied and the results indicated that compounds (1 and 2) showed almost no cytotoxicityat at a concentration of 150 µg·mL-1. The interacted mechanism was the thiolysis reaction of dinitrophenyl ether which had been confirmed by fluorescence and HRMS titration experiment. In addition, probe 1 can also detect HS- selectively by naked eye in pure DMSO solvent.