Construction of Potential Glioblastoma Multiforme-Related miRNA-mRNA Regulatory Network

Background: Glioblastoma multiforme (GBM), the most common and aggressive human malignant brain tumor, is notorious for its limited treatment options and poor prognosis. MicroRNAs (miRNAs) are found to be involved in tumorigenesis of GBM. However, a comprehensive miRNA-mRNA regulatory network has still not been established.Methods: A miRNA microarray dataset (GSE90603) was obtained from GEO database. Then, we employed GEO2R tool to perform differential expression analysis. Potential transcription factors and target genes of screened differentially expressed miRNAs (DE-miRNAs) were predicted. The GBM mRNA dataset were downloaded from TCGA database for identifying differentially expressed genes (DEGs). Next, GO annotation and KEGG pathway enrichment analysis was conducted. PPI network was then established, and hub genes were identified via Cytoscape software. The expression and prognostic roles of hub genes was further evaluated.Results: Total 33 DE-miRNAs, consisting of 10 upregulated DE-miRNAs and 23 downregulated DE-miRNAs, were screened. SP1 was predicted to potentially regulate most of screened DE-miRNAs. Three thousand and twenty seven and 3,879 predicted target genes were obtained for upregulated and downregulated DE-miRNAs, respectively. Subsequently, 1,715 upregulated DEGs and 1,259 downregulated DEGs were identified. Then, 149 and 295 potential downregulated and upregulated genes commonly appeared in target genes of DE-miRNAs and DEGs were selected for GO annotation and KEGG pathway enrichment analysis. The downregulated genes were significantly enriched in cGMP-PKG signaling pathway and calcium signaling pathway whereas the upregulated genes were enriched in pathways in cancer and PI3K-Akt signaling pathway. Construction and analysis of PPI network showed that STXBP1 and TP53 were recognized as hub genes with the highest connectivity degrees. Expression analytic result of the top 20 hub genes in GBM using GEPIA database was generally identical with previous differential expression analysis for TCGA data. EGFR, PPP3CB, and MYO5A expression was significantly associated with patients' OS.Conclusions: In this study, we established a potential GBM-related miRNA-mRNA regulatory network, which explores a comprehensive understanding of the molecular mechanisms and provides key clues in seeking novel therapeutic targets for GBM. In the future, more experiments need to be performed to validate our current findings

Phenomenological modeling of Geometric Metasurfaces

Metasurfaces, with their superior capability in manipulating the optical wavefront at the subwavelength scale and low manufacturing complexity, have shown great potential for planar photonics and novel optical devices. However, vector field simulation of metasurfaces is so far limited to periodic-structured metasurfaces containing a small number of meta-atoms in the unit cell by using full-wave numerical methods. Here, we propose a general phenomenological method to analytically model metasurfaces made up of arbitrarily distributed meta-atoms based on the assumption that the meta-atoms possess localized resonances with Lorentz-Drude forms, whose exact form can be retrieved from the full wave simulation of a single element. Applied to phase modulated geometric metasurfaces, our analytical results show good agreement with full-wave numerical simulations. The proposed theory provides an efficient method to model and design optical devices based on metasurfaces.Comment: 16 pages, 8 figure

Spectroscopy of broad absorption line quasars at 3≲z≲53\lesssim z \lesssim 5 -- I: evidence for quasar winds shaping broad/narrow emission line regions

We present an observational study of 22 broad absorption line quasars (BAL QSOs) at $3\lesssim z \lesssim5$ based on optical/near-IR spectroscopy, aiming to investigate quasar winds and their effects. The near-IR spectroscopy covers the \hb\ and/or \mgii\ broad emission lines (BELs) for these quasars, allowing us to estimate their central black hole (BH) masses in a robust way. We found that our BAL QSOs on average do not have a higher Eddington ratio than that from non-BAL QSOs matched in redshift and/or luminosity. In a subset consisting of seven strong BAL QSOs possessing sub-relativistic BAL outflows, we see the prevalence of large \civ-BEL blueshift ($\sim$3100 km s$^{-1}$) and weak \oiii\ emission (particularly the narrow \oiii$\lambda$5007 component), indicative of nuclear outflows affecting the narrow emission-line (NEL) regions. In another subset consisting of thirteen BAL QSOs having simultaneous observations of \mgii\ and \hb, we found a strong correlation between 3000~\AA\ and 5000~\AA\ monochromatic luminosity, consistent with that from non-BAL QSOs matched in redshift and luminosity; however, there is no correlation between \mgii\ and \hb\ in FWHM, likely due to nuclear outflows influencing the BEL regions. Our spectroscopic investigations offer strong evidence that the presence of nuclear outflows plays an important role in shaping the BEL/NEL regions of these quasars and possibly, regulating the growth of central supermassive black holes (SMBHs). We propose that BEL blueshift and BAL could be different manifestations of the same outflow system viewed at different sightlines and/or phases.Comment: 13 pages, 10 figures. Accepted for publication in Ap

NDH-1 Is Important for Photosystem I Function of Synechocystis sp. Strain PCC 6803 under Environmental Stress Conditions

Cyanobacterial NDH-1 interacts with photosystem I (PSI) to form an NDH-1-PSI supercomplex. Here, we observed that absence of NDH-1 had little, if any, effect on the functional fractions of PSI under growth conditions, but significantly reduced the functional fractions of PSI when cells of Synechocystis sp. strain PCC 6803 were moved to conditions of multiple stresses. The significant reduction in NDH-1-dependent functional fraction of PSI was initiated after PSII activity was impaired. This finding is consistent with our observation that the functional fraction of PSI under growth conditions was rapidly and significantly decreased with increasing concentrations of DCMU, which rapidly and significantly suppressed PSII activity by blocking the transfer of electrons from QA to QB in the PSII reaction center. Furthermore, absence of NDH-1 resulted in the PSI limitation at the functionality of PSI itself but not its donor-side and acceptor-side under conditions of multiple stresses. This was supported by the result of a significant destabilization of the PSI complex in the absence of NDH-1 but the presence of multiple stresses. Based on the above results, we propose that NDH-1 is important for PSI function of Synechocystis sp. strain PCC 6803 mainly via maintaining stabilization of PSI under conditions of environmental stresses.This work was supported by the National Natural Science Foundation of China (grant nos. 31370270, 31570235, 31770259, and 31700205), China Postdoctoral Science Foundation (grant nos. 2015M581643 and 2017T100304), Shanghai Science and Technology Committee (grant no. 17070502900) and Project of Shanghai Normal University (grant no. SK201705)

QR-CLIP: Introducing Explicit Open-World Knowledge for Location and Time Reasoning

Daily images may convey abstract meanings that require us to memorize and infer profound information from them. To encourage such human-like reasoning, in this work, we teach machines to predict where and when it was taken rather than performing basic tasks like traditional segmentation or classification. Inspired by Horn's QR theory, we designed a novel QR-CLIP model consisting of two components: 1) the Quantity module first retrospects more open-world knowledge as the candidate language inputs; 2) the Relevance module carefully estimates vision and language cues and infers the location and time. Experiments show our QR-CLIP's effectiveness, and it outperforms the previous SOTA on each task by an average of about 10% and 130% relative lift in terms of location and time reasoning. This study lays a technical foundation for location and time reasoning and suggests that effectively introducing open-world knowledge is one of the panaceas for the tasks.Comment: Technical Report. Github: https://github.com/Shi-Wm/QR-CLI

An ultra-luminous quasar with a twelve-billion-solar-mass black hole at redshift 6.30

So far, roughly 40 quasars with redshifts greater than z=6 have been discovered. Each quasar contains a black hole with a mass of about one billion solar masses ($10^9 M_\odot$). The existence of such black holes when the Universe was less than 1 billion years old presents substantial challenges to theories of the formation and growth of black holes and the coevolution of black holes and galaxies. Here we report the discovery of an ultra-luminous quasar, SDSS J010013.02+280225.8, at redshift z=6.30. It has an optical and near-infrared luminosity a few times greater than those of previously known z>6 quasars. On the basis of the deep absorption trough on the blue side of the Ly $\alpha$ emission line in the spectrum, we estimate the proper size of the ionized proximity zone associated with the quasar to be 26 million light years, larger than found with other z>6.1 quasars with lower luminosities. We estimate (on the basis of a near-infrared spectrum) that the black hole has a mass of $\sim 1.2 \times 10^{10} M_\odot$, which is consistent with the $1.3 \times 10^{10} M_\odot$ derived by assuming an Eddington-limited accretion rate.Comment: 24 pages, 4 figures plus 4 extended data figures, published in Nature on 26 February 201