Florofangchinoline inhibits proliferation of osteosarcoma cells via targeting of histone H3 lysine 27 trimethylation and AMPK activation

Purpose: To investigate the effect of florofangchinoline on osteosarcoma cell growth in vitro, and the underlying mechanism of action.Methods: Changes in the viability of KHOS and Saos-2 cells were measured using water soluble tetrazolium salt (WST) assay, while apoptosis was determined using Annexin V/PI staining and flow cytometry. Increases in mtDNA, and expressions of PGC-1α and TFAM were assayed with immunoblot analysis and quantitative real-time polymerase chain reaction (qPCR), respectively.Results: Microscopic examination of florofangchinoline-treated cells showed significant decrease in cell density, relative to control cells (p < 0.05). Treatment with 10 μM florofangchinoline increased apoptosis in KHOS and Saos-2 cells to 56.32 and 63.75 %, respectively (p < 0.05). Florofangchinoline treatment markedly enhanced cleavage of caspase-3, caspase-8, caspase-9 and PARP. It elevated Bax level and reduced Bcl-2 in KHOS and Saos-2 cells. Moreover, florofangchinoline increased p21 and p-AMPKα levels, and mtDNA counts in KHOS and Saos-2 cells (p < 0.05). Moreover, in florofangchinoline-treated KHOS cells, the expressions of EED, EZH2 and SUZ12 were significantly suppressed (p < 0.05).Conclusion: Florofangchinoline inhibits osteosarcoma cell viability by activation of apoptosis. Moreover, it activates AMPK and down-regulates  histone H3 lysine 27 trimethylation in osteosarcoma cells. Therefore, florofangchinoline has potentials for development as a therapeutic drug forosteosarcoma. Keywords: Osteosarcoma, Histone H3, Florofangchinoline, Apoptosis, Chemotherapeuti

TRIP13 Enhances Radioresistance of Lung Adenocarcinoma Cells through the Homologous Recombination Pathway

Background and objective Radiation therapy is one of the most common treatments for non-small cell lung cancer (NSCLC). However, the insensitivity of some tumor cells to radiation is one of the major reasons for the poor efficacy of radiotherapy and the poor prognosis of patients, and exploring the underlying mechanisms behind radioresistance is the key to solving this clinical challenge. This study aimed to identify the molecules associated with radioresistance in lung adenocarcinoma (LUAD), identified thyroid hormone receptor interactor 13 (TRIP13) as the main target initially, and explored whether TRIP13 is related to radioresistance in LUAD and the specific mechanism, with the aim of providing theoretical basis and potential targets for the combination therapy of LUAD patients receiving radiotherapy in the clinic. Methods Three datasets, GSE18842, GSE19188 and GSE33532, were selected from the Gene Expression Omnibus (GEO) database and screened for differentially expressed genes (|log FC|>1.5, P<0.05) in each of the three datasets using the R 4.1.3 software, and then Venn diagram was used to find out the differentially expressed genes common to the three datasets. The screened differential genes were then subjected to protein-protein interaction (PPI) analysis and module analysis with the help of STRING online tool and Cytoscape software, and survival prognosis analysis was performed for each gene with the help of Kaplan-Meier Plotter database, and the TRIP13 gene was identified as the main molecule for subsequent studies. Subsequently, the human LUAD cell line H292 was irradiated with multiple X-rays using a sub-lethal dose irradiation method to construct a radioresistant cell line, H292DR. The radioresistance of H292DR cells was verified using cell counting kit-8 (CCK-8) assay and clone formation assay. The expression levels of TRIP13 in H292 and H292DR cells were measured by Western blot. Small interfering RNA (siRNA) was used to silence the expression of TRIP13 in H292DR cells and Western blot assay was performed. The clone formation ability and migration ability of H292DR cells were observed after TRIP13 silencing, followed by the detection of changes in the expression levels of proteins closely related to homologous recombination, such as ataxia telangiectasia mutated (ATM) protein. Results Screening of multiple GEO datasets, validation of external datasets and survival analysis revealed that TRIP13 was highly expressed in LUAD and was associated with poor prognosis in LUAD patients who had received radiation therapy. And the results of gene set enrichment analysis (GSEA) of TRIP13 suggested that TRIP13 might be closely associated with LUAD radioresistance by promoting homologous recombination repair after radiation therapy. Experimentally, TRIP13 expression was found to be upregulated in H292DR, and silencing of TRIP13 was able to increase the sensitivity of H292DR cells to radiation. Conclusion TRIP13 is associated with poor prognosis in LUAD patients treated with radiation, possibly by promoting a homologous recombination repair pathway to mediate resistance of LUAD cells to radiation

Dual-Color Lasing Lines from EMPs in Diluted Magnetic Semiconductor CdS:NiI Structure

Have one ever seen a semiconductor that can issue two-color lasing lines? The diluted magnetic semiconductor (DMS) can do this. Here, we have observed dual lasing lines of 530 nm and 789 nm from a DMS structure of CdS:NiI, in which the excitonic magnetic polaron (EMP) and localized excitonic magnetic polaron (LEMP) are excitations out of ferromagnetic (NiS)x nanocluster and NiI2 nanoclusters within CdS lattice; both of them could lead to the collective EMP state at high excitation and therein produce coherent emission lines simultaneously. This occurrence is due to the superposition of EMP near CdS bandedge and the combination of the charge-transfer band of (NiI)n cluster with the LEMP within CdS lattice by overcoming the strong electron correlation of NiI cluster in a DMS structure, evidenced also by ab initio calculation. This finding opens a way to understand the collective behaviour of spin-coupled excitons in DMS and to find novel applications in the spin-related quantum technology

The enhanced x-ray timing and polarimetry mission – eXTP: an update on its scientific cases, mission profile and development status

The enhanced x-ray timing and polarimetry mission (eXTP) is a flagship observatory for x-ray timing, spectroscopy and polarimetry developed by an international consortium. Thanks to its very large collecting area, good spectral resolution and unprecedented polarimetry capabilities, eXTP will explore the properties of matter and the propagation of light in the most extreme conditions found in the universe. eXTP will, in addition, be a powerful x-ray observatory. The mission will continuously monitor the x-ray sky, and will enable multi-wavelength and multi-messenger studies. The mission is currently in phase B, which will be completed in the middle of 2022