BackgroundMultiple myeloma (MM) accounts for 10% of all hematological malignancies. Dysregulation of microRNAs (miRNAs) or long non-coding RNAs (lncRNAs) has important impacts on progression of MM. Circular RNAs (circRNAs) are correlated with malignancy in the modulation of tumor progression. This study aims to investigate the effect of circ_0000190 on regulating the progression of MM.MethodMicroscopic examination via single molecule fluorescent in situ hybridization indicates the location of circ_0000190. qRT-PCR and Western blot were used to evaluate the expression of RNAs and proteins. Potential target of circ_0000190 was searched as miRNA, and examined by luciferase reporter assay. A computational screen was also conducted to search the potential target of miRNA. In vitro cell viability, proliferation, apoptosis assays and flow cytometric were performed to assess the effects of circ_0000190 and its target on MM. Mice model of human MM was established with subcutaneous xenograft tumor, qRT-PCR and western blot were performed to detect the underlying mechanisms of circ_0000190 on MM.ResultsCirc_0000190 was located in the cytoplasm, and down-regulated in both bone marrow tissue and peripheral blood, while the target of circ_0000190, miR-767-5p, was up-regulated, suggesting a negative correlation between them. The binding ability between circ_0000190 and miR-767-5p was confirmed by luciferase reporter assay. Moreover, circ_0000190 inhibited cell viability, proliferation and induced apoptosis of MM thus inhibiting cell progression, which is partially through the negative regulation of miR-767-5p. Mitogen-activated protein kinase 4 (MAPK4) is a direct target of miR-767-5p. In addition, over-expression of miR-767-5p promoted cell progression by directly targeting and regulating MAPK4. The MM model mice with administration of circ_0000190 suppressed tumor growth and progression.ConclusionOur results revealed that the ability of circ_0000190 to protect against MM was inherited through repression of miR-767-5p, and miR-767-5p might be a tumor drive through targeting MAPK4. Therefore, a novel role of circ_0000190 on regulating the progression of MM was found, and the clinical application of circRNAs might represent a strategy in MM.Electronic supplementary materialThe online version of this article (10.1186/s13046-019-1071-9) contains supplementary material, which is available to authorized users.

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Human pluripotent stem cells (hPSCs) exhibit very limited contribution to interspecies chimeras. One explanation is that the conventional hPSCs are in a primed state and so unable  to form chimeras in pre-implantation embryos. Here, we show that the conventional hPSCs undergo rapid apoptosis when injected into mouse pre-implantation embryos. While, forced-expression of BMI1, a polycomb factor in hPSCs overcomes the apoptosis and enables hPSCs to integrate into mouse pre-implantation embryos and subsequently contribute to chimeras with both embryonic and extra-embryonic tissues. In addition, BMI1 also enables hPSCs to integrate into pre-implantation embryos of other species, such as rabbit and pig. Notably, BMI1 high expression and anti-apoptosis are also indicators for naïve hPSCs to form chimera in mouse embryos. Together, our findings reveal that the apoptosis is an initial barrier in interspecies chimerism using hPSCs and provide a rational to improve it.

The authors declare that they have no conflicts of interest with the contents of this article. This article contains Figs. S1-S6 and Tables S1 and S2. The RNA-seq, ATAC-seq, and ChIP-seq data reported in this paper can be assessed under GEO GSE132970.

Jiaming Gu,a Xiaodong Sun,b Xinyao Liu,a Yang Yuan,a Hongyan Shan,a and Yunling Liu*a To systematically study the effect of Lewis acid sites (LASs) and Lewis basic sites (LBSs) in MOFs...

With the help of modulator synthesis method, a mesoporous Zr-based metal–organic framework, [Zr6O4(OH)8(H2O)4­(TADIBA)4]·24DMF·45H2O (DMF = N,N-dimethylformamide, H2TADIBA = 4,4′-(2H-1,2,4-triazole-3,5-diyl) dibenzoic acid), namely, JLU-MOF58, was successfully constructed. JLU-MOF58 having reo topology is constructed by the bent ligands with Lewis basic sites and 8-connected Zr6 clusters with Lewis and Brønsted acid sites. It not only possesses two types of mesoporous cages: octahedral and cuboctahedral (2.76 and 4.10 nm), with a pore volume of 1.76 cm3 g–1, but also displays excellent chemical stability in acid and base aqueous phase. Benefiting from the Brønsted and Lewis acid sites, Lewis basic sites, excellent chemical stability, and the mesoporous cages incorporated in the framework, JLU-MOF58 can be regarded as a remarkably efficient heterogeneous catalyst that exhibits excellent catalytic efficiency for CO2 conversion.

On the basis of different V-shaped ligands, three zirconium−organic frameworks (JLU-Liu45, Zr-SDBA, and Zr-OBBA) have been successfully constructed. By regulating spatial configuration and functional groups of organic ligands, these assynthesized Zr-MOFs (MOF = metal−organic framework) display distinct structures and different light hydrocarbon adsorption/ separation capabilities. JLU-Liu45, with a double-walled interpenetrated 3D primitive cubic (pcu) framework, exhibits good gasadsorption capacity but not prominent selective separation ability. Through regulating sizes and torsion angles of the organic ligands, Zr-SDBA possesses a 2D square lattice (sql) network, while Zr-OBBA displays a non-interpenetrated 3D pcu framework. Furthermore, by regulating functional groups on the ligands, Zr-SDBA shows prominent C 2 H 2 uptake (101.2 cm 3 •g −1 ) and the best C 2 H 2 /CH 4 selectivity (230.5, 1:1) among the three Zr-MOFs, and Zr-OBBA shows a significant C 3 H 8 /CH 4 selectivity (105.6, 1:1). This work demonstrates the feasibility of structural regulation for MOF materials in the light hydrocarbon adsorption/separation field.

Definitive hematopoiesis generates hematopoietic stem/progenitor cells (HSPCs) that give rise to all mature blood and immune cells, but remains poorly defined in human. Here, we resolve human hematopoietic populations at the earliest hematopoiesis stage by single-cell RNA-seq. We characterize the distinct molecular profiling between early primitive and definitive hematopoiesis in both human embryonic stem cell (hESC) differentiation and early embryonic development. We identify CD44 to specifically discriminate definitive hematopoiesis and generate definitive HSPCs from hESCs. The multipotency of hESCs-derived HSPCs for various blood and immune cells is validated by single-cell clonal assay. Strikingly, these hESCs-derived HSPCs give rise to blood and lymphoid lineages in vivo. Lastly, we characterize gene-expression dynamics in definitive and primitive hematopoiesis and reveal an unreported role of ROCK-inhibition in enhancing human definitive hematopoiesis. Our study provides a prospect for understanding human early hematopoiesis and a firm basis for generating blood and immune cells for clinical purposes.