Screening hub genes in coronary artery disease based on integrated analysis

Background: Coronary artery disease (CAD) is the leading cause of mortality worldwide. Identifying key pathogenic genes benefits the understanding molecular mechanism of CAD. Methods: In this study, 5 microarray data sets from the blood sample of 312 CADs and 277 healthy controls were downloaded. Limma and metaMA packages were used to identify differentially expressed genes. The functional enrichment analysis of differentially expressed genes was further performed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Additionally, protein–protein interac­tion and transcript factors-target networks were performed based on top 10 up- and down-regulated differentially expressed genes to further study the biological function. Last, real-time quantitative poly­merase chain reaction (RT-qPCR) was used to validate the integrated analysis result. Results: A total of 528 differentially expressed genes were obtained. All differentially expressed genes were significantly involved in signal transduction and the MAPK signaling pathway. Among MAPK signaling pathway, IL1R2, ARRB2 and PRKX were associated with CAD. Furthermore, there were 4 common differentially expressed genes including PLAUR, HSPH1, ZMYND11 and S100A8 in the protein–protein interaction and transcript factors-target networks, which played crucial roles in the development of CAD. In quantitative RT-qPCR, the expression of PRKX, HSPH1 and ZMYND11 was down-regulated and consistent with the integrated analysis. Conclusions: Identified 7 differentially expressed genes (IL1R2, ARRB2, PRKX, PLAUR, HSPH1, ZMYND11 and S100A8) may play crucial roles in the development of CAD

Amphiregulin-EGFR Signaling Mediates the Migration of Bone Marrow Mesenchymal Progenitors toward PTH-Stimulated Osteoblasts and Osteocytes

Intermittent administration of parathyroid hormone (PTH) dramatically increases bone mass and currently is one of the most effective treatments for osteoporosis. However, the detailed mechanisms are still largely unknown. Here we demonstrate that conditioned media from PTH-treated osteoblastic and osteocytic cells contain soluble chemotactic factors for bone marrow mesenchymal progenitors, which express a low amount of PTH receptor (PTH1R) and do not respond to PTH stimulation by increasing cAMP production or migrating toward PTH alone. Conditioned media from PTH-treated osteoblasts elevated phosphorylated Akt and p38MAPK amounts in mesenchymal progenitors and inhibition of these pathways blocked the migration of these progenitors toward conditioned media. Our previous and current studies revealed that PTH stimulates the expression of amphiregulin, an epidermal growth factor (EGF)-like ligand that signals through the EGF receptor (EGFR), in both osteoblasts and osteocytes. Interestingly, conditioned media from PTH-treated osteoblasts increased EGFR phosphorylation in mesenchymal progenitors. Using several different approaches, including inhibitor, neutralizing antibody, and siRNA, we demonstrate that PTH increases the release of amphiregulin from osteoblastic cells, which acts on the EGFRs expressed on mesenchymal progenitors to stimulate the Akt and p38MAPK pathways and subsequently promote their migration in vitro. Furthermore, inactivation of EGFR signaling specifically in osteoprogenitors/osteoblasts attenuated the anabolic actions of PTH on bone formation. Taken together, these results suggest a novel mechanism for the therapeutic effect of PTH on osteoporosis and an important role of EGFR signaling in mediating PTH's anabolic actions on bone

SiMaN: Sign-to-Magnitude Network Binarization

Binary neural networks (BNNs) have attracted broad research interest due to their efficient storage and computational ability. Nevertheless, a significant challenge of BNNs lies in handling discrete constraints while ensuring bit entropy maximization, which typically makes their weight optimization very difficult. Existing methods relax the learning using the sign function, which simply encodes positive weights into +1s, and -1s otherwise. Alternatively, we formulate an angle alignment objective to constrain the weight binarization to {0,+1} to solve the challenge. In this paper, we show that our weight binarization provides an analytical solution by encoding high-magnitude weights into +1s, and 0s otherwise. Therefore, a high-quality discrete solution is established in a computationally efficient manner without the sign function. We prove that the learned weights of binarized networks roughly follow a Laplacian distribution that does not allow entropy maximization, and further demonstrate that it can be effectively solved by simply removing the $\ell_2$ regularization during network training. Our method, dubbed sign-to-magnitude network binarization (SiMaN), is evaluated on CIFAR-10 and ImageNet, demonstrating its superiority over the sign-based state-of-the-arts. Our source code, experimental settings, training logs and binary models are available at https://github.com/lmbxmu/SiMaN

Synergy between CSST galaxy survey and gravitational-wave observation: Inferring the Hubble constant from dark standard sirens

Gravitational waves (GWs) from compact binary coalescences encode the absolute luminosity distances of GW sources. Once the redshifts of GW sources are known, one can use the distance-redshift relation to constrain cosmological parameters. One way to obtain the redshifts is to localize GW sources by GW observations and then use galaxy catalogs to determine redshifts from a statistical analysis of redshift information of the potential host galaxies, commonly referred to as the dark siren method. The third-generation (3G) GW detectors are planned to work in the 2030s and will observe numerous compact binary coalescences. Using these GW events as dark sirens requires high-quality galaxy catalogs from future sky survey projects. The China Space Station Telescope (CSST) will be launched in 2024 and will observe billions of galaxies within a 17500 deg$^2$ survey area with redshift up to $z\sim 4$, providing photometric and spectroscopic galaxy catalogs. In this work, we simulate the CSST galaxy catalogs and the 5-year GW data from the 3G GW detectors and combine them to infer the Hubble constant ($H_0$). Our results show that the measurement precision of $H_0$ could reach the sub-percent level, meeting the standard of precision cosmology. We conclude that the synergy between CSST and the 3G GW detectors is of great significance in measuring the Hubble constant.Comment: 13 pages, 5 figure

Robust Preamble-Based Timing Synchronization for OFDM Systems

This study presents a novel preamble-based timing offset estimation method for orthogonal frequency division multiplexing (OFDM) systems. The proposed method is robust, immune to the carrier frequency offset (CFO), and independent of the structure of the preamble. The performance of the new method is demonstrated in terms of mean square error (MSE) obtained by simulation in multipath fading channels. The results indicate that the new method significantly improves timing performance in comparison with existing methods

Reduced EGFR signaling enhances cartilage destruction in a mouse osteoarthritis model

Osteoarthritis (OA) is a degenerative joint disease and a major cause of pain and disability in older adults. We have previously identified epidermal growth factor receptor (EGFR) signaling as an important regulator of cartilage matrix degradation during epiphyseal cartilage development. To study its function in OA progression, we performed surgical destabilization of the medial meniscus (DMM) to induce OA in two mouse models with reduced EGFR activity, one with genetic modification (Egfr Wa5/+ mice) and the other one with pharmacological inhibition (gefitinib treatment). Histological analyses and scoring at 3 months post-surgery revealed increased cartilage destruction and accelerated OA progression in both mouse models. TUNEL staining demonstrated that EGFR signaling protects chondrocytes from OA-induced apoptosis, which was further confirmed in primary chondrocyte culture. Immunohistochemistry showed increased aggrecan degradation in these mouse models, which coincides with elevated amounts of ADAMTS5 and matrix metalloproteinase 13 (MMP13), the principle proteinases responsible for aggrecan degradation, in the articular cartilage after DMM surgery. Furthermore, hypoxia-inducible factor 2α (HIF2α), a critical catabolic transcription factor stimulating MMP13 expression during OA, was also upregulated in mice with reduced EGFR signaling. Taken together, our findings demonstrate a primarily protective role of EGFR during OA progression by regulating chondrocyte survival and cartilage degradation