TSPYL2 Is Important for G1 Checkpoint Maintenance upon DNA Damage

Nucleosome assembly proteins play important roles in chromatin remodeling, which determines gene expression, cell proliferation and terminal differentiation. Testis specific protein, Y-encoded-like 2 (TSPYL2) is a nucleosome assembly protein expressed in neuronal precursors and mature neurons. Previous studies have shown that TSPYL2 binds cyclin B and inhibits cell proliferation in cultured cells suggesting a role in cell cycle regulation. To investigate the physiological significance of TSPYL2 in the control of cell cycle, we generated mice with targeted disruption of Tspyl2. These mutant mice appear grossly normal, have normal life span and do not exhibit increased tumor incidence. To define the role of TSPYL2 in DNA repair, checkpoint arrest and apoptosis, primary embryonic fibroblasts and thymocytes from Tspyl2 deficient mice were isolated and examined under unperturbed and stressed conditions. We show that mutant fibroblasts are impaired in G1 arrest under the situation of DNA damage induced by gamma irradiation. This is mainly attributed to the defective activation of p21 transcription despite proper p53 protein accumulation, suggesting that TSPYL2 is additionally required for p21 induction. TSPYL2 serves a biological role in maintaining the G1 checkpoint under stress condition

Differential Proteome Analysis of Bone Marrow Mesenchymal Stem Cells from Adolescent Idiopathic Scoliosis Patients

Adolescent idiopathic scoliosis (AIS) is a complex three-dimensional deformity of the spine. The cause and pathogenesis of scoliosis and the accompanying generalized osteopenia remain unclear despite decades of extensive research. In this study, we utilized two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MS) to analyze the differential proteome of bone marrow mesenchymal stem cells (BM-MSCs) from AIS patients. In total, 41 significantly altered protein spots were detected, of which 34 spots were identified by MALDI-TOF/TOF analysis and found to represent 25 distinct gene products. Among these proteins, five related to bone growth and development, including pyruvate kinase M2, annexin A2, heat shock 27 kDa protein, γ-actin, and β-actin, were found to be dysregulated and therefore selected for further validation by Western blot analysis. At the protein level, our results supported the previous hypothesis that decreased osteogenic differentiation ability of MSCs is one of the mechanisms leading to osteopenia in AIS. In summary, we analyzed the differential BM-MSCs proteome of AIS patients for the first time, which may help to elucidate the underlying molecular mechanisms of bone loss in AIS and also increase understanding of the etiology and pathogenesis of AIS

Automatic Concept Extraction Based on Semantic Graphs From Big Data in Smart City

With the rapid development of smart cities, various types of sensors can rapidly collect a large amount of data, and it becomes increasingly important to discover effective knowledge and process information from massive amounts of data. Currently, in the field of knowledge engineering, knowledge graphs, especially domain knowledge graphs, play important roles and become the infrastructure of Internet knowledge-driven intelligent applications. Domain concept extraction is critical to the construction of domain knowledge graphs. Although there have been some works that have extracted concepts, semantic information has not been fully used. However, the excellent concept extraction results can be obtained by making full use of semantic information. In this article, a novel concept extraction method, Semantic Graph-Based Concept Extraction (SGCCE), is proposed. First, the similarities between terms are calculated using the word co-occurrence, the LDA topic model and Word2Vec. Then, a semantic graph of terms is constructed based on the similarities between the terms. Finally, according to the semantic graph of the terms, community detection algorithms are used to divide the terms into different communities where each community acts as a concept. In the experiments, we compare the concept extraction results that are obtained by different community detection algorithms to analyze the different semantic graphs. The experimental results show the effectiveness of our proposed method. This method can effectively use semantic information, and the results of the concept extraction are better from domain big data in smart cities. IEEEThis work was supported in part by the National Key Research and Development Plan under Grant 2018YFB0803504 and Grant 2018YEB1004003, in part by the Guangdong Province Key Research and Development Plan under Grant 2019B010137004, in part by the National Natural Science Foundation of China under Grant 61871140, Grant 61872100, Grant 61572153, and Grant U1636215, and in part by the Peng Cheng Laboratory Project of Guangdong Province under Grant PCL2018KP004.Scopu

Using MTF with fixed-zoning method for automated gated imaging system in turbid medium

236-241For a typical gated system, the gated images are recorded into video format in increasing gate opening time, each frame of the video recorded is basically to “slice” the targets at different distance from camera (based on time of light). In this paper, all enhanced target images within the field of view (FOV) are fused into one 3D image. Works had been done in 1) selecting a quantitative image quality index for automated tuning system so that sectioned images with better quality can be detected accurately in turbid condition and 2) applying a fixed zoning system - sectioning method by splitting input images into 25 equal sub-images to demonstrate the concept of flexible zoning method in future works. Modulation Transfer Function (MTF) can perform better in analyzing images under turbid condition thus is selected for this application. Experiment results show that the mid-band spatial frequencies from 21 to 61 demonstrate the degradation of image quality due to the turbid water backscattering noises. Thus, we propose to use MTF in the auto-tuning system to select best quality target from multiple images. Subsequently, image fusion is performed to fuse all selected sub-images into 3D extended targets in turbid condition

In Vitro Investigation of the Cytotoxic Activity of Emodin 35 Derivative on Multiple Myeloma Cell Lines

Background. Bortezomib is used for treating multiple myeloma (MM); however, it has considerable adverse effects. Emodin has been reported to exhibit inhibitory effects on MM cell lines. We investigated the efficacy of emodin 35 (E35), an emodin derivative, using U266 and MM1s cell lines in treating MM and the efficacy of combining bortezomib and E35. Methods. MTT assays were used to observe the effects of E35 on MM cell growth. The effects on cellular apoptosis were then observed using Annexin V/propidium iodide (PI) staining assay. The expression of apoptosis-related genes, including the caspase family, was examined. The efficacy of combining bortezomib and E35 was investigated by examining the expression of the Akt/mTOR/4EBP1 signaling pathway-related proteins. Results. We report that E35 inhibited the growth of U266 and MM1s cells by inducing cellular apoptosis. Moreover, E35 downregulated the expression of apoptosis-related genes and suppressed the phosphorylation of Akt/mTOR/4EBP1 signaling pathway-related genes, thus exhibiting synergistic effects with bortezomib. All observed effects were dose-dependent. Conclusion. The results showed that E35 exhibited cytotoxic effects in MM cell lines in protein levels. Thus, E35, particularly in combination with bortezomib, may be considered as a promising treatment for MM; however, this requires further investigation in vivo

Facile and Reliable in Situ Polymerization of Poly(Ethyl Cyanoacrylate)-Based Polymer Electrolytes toward Flexible Lithium Batteries

Polycyanoacrylate is a very promising matrix for polymer electrolyte, which possesses advantages of strong binding and high electrochemical stability owing to the functional nitrile groups. Herein, a facile and reliable in situ polymerization strategy of poly­(ethyl cyanoacrylate) (PECA) based gel polymer electrolytes (GPE) via a high efficient anionic polymerization was introduced consisting of PECA and 4 M LiClO₄ in carbonate solvents. The in situ polymerized PECA gel polymer electrolyte achieved an excellent ionic conductivity (2.7 × 10^–3 S cm^–1) at room temperature, and exhibited a considerable electrochemical stability window up to 4.8 V vs Li/Li⁺. The LiFePO₄/PECA-GPE/Li and LiNi_1.5Mn_0.5O₄/PECA-GPE/Li batteries using this in-situ-polymerized GPE delivered stable charge/discharge profiles, considerable rate capability, and excellent cycling performance. These results demonstrated this reliable in situ polymerization process is a very promising strategy to prepare high performance polymer electrolytes for flexible thin-film batteries, micropower lithium batteries, and deformable lithium batteries for special purpose

Dynamic 3D morphology of chick embryos and allantois depicted nondestructively by 3.0T clinical magnetic resonance imaging

ABSTRACT: Driven by a global trend of applying replace-reduce-refine or 3Rs’ guidance for experimental animals in life sciences, chick embryo and particularly allantois with its chorioallantoic membrane have been increasingly utilized to substitute laboratory animals, which call for more extensive and updated knowledge about this novel experimental setup. In this study, being noninvasive, nonionizing, and super-contrasting with high spatiotemporal resolutions, magnetic resonance imaging (MRI) was chosen as an imaging modality for in ovo monitoring morphologic evolution of the chick embryo, allantois, and chorioallantoic membrane longitudinally throughout embryonic day (ED) 1 until ED20. Cooled in 0°C ice bath for 60 min to reduce MRI motion artifacts, 3 chick embryos (n = 60 in total) on each ED were scanned by a clinical 3.0T MRI scanner to demonstrate 3D images of both T2- and T1-weighted imaging (T2WI, T1WI) sequences at axial, sagittal, and coronal slices. The volumes of both the entire chick embryo and allantois were semi-automatically segmented based on intensity-based thresholding and region-growing algorithms. The morphometries or quantified 3D structures were achieved by refined segmentation, and confirmed by histological analyses (one for each ED). After MRI, the rest of chick embryos (n = 40) continued for incubation. The images from ED2 to ED4 could demonstrate the structural changes of latebra, suggesting its transition into a nutrient supplying channel of yolk sac. The allantois could be recognized by MRI, and its relative volumes on each ED revealed an evolving profile peaked on ED12, with a statistically significant difference from those of earlier and later EDs (P < 0.01). The hypointensity of the yolk due to the susceptibility effect of its enriched iron content overshadowed the otherwise hyperintensity of its lipid components. The chick embryos survived prior cooling and MRI till hatching on ED21. The results could be further developed into a 3D MRI atlas of chick embryo. Clinical 3.0T MRI proved effective as a noninvasive approach to study in ovo 3D embryonic development across the full period (ED1–ED20), which can complement the present knowhow for poultry industry and biomedical science

Urinary Trypsin Inhibitor Attenuates Acute Lung Injury by Improving Endothelial Progenitor Cells Functions

Background: Urinary Trypsin Inhibitor (UTI) is involved in various aspects of tissue repair, regeneration and development. However, the potential role of UTI in protection against acute lung injury (ALI) remains largely unknown. In the present study, we demonstrated that UTI treatment could ameliorate ALI induced by oleic acid (OA) treatment in rabbit model. Methods: Intravenous application of UTI (10000 U/kg/d) significantly improved the pathologies associated with OA-induced ALI. The lungs were stained with hematoxylin and eosin to scored the lung injury. Peripheral blood mononuclear cells were isolated by density gradient centrifugation with Ficoll-Plaque Plus. The proliferation and ability of tube structure formation of EPCs were observed and the level of phosphorylated Akt protein expression and eNOS protein expression were assayed. Results: Consistent with pathological scores, UTI treatment significantly reduced wet/dry ratio of OA injured lungs. A quantification of capillary density revealed that UTI treatment led to about 2 fold increase over uninjured control and about 1.5 fold increase over PBS treatment. The capacity for tube formation of EPCs on ECM gel was significantly reduced in the ALI group and recovered with UTI treatment. Quantification of western blot bands was summarized and showed that UTI treatment activates Akt/eNOS signaling. NO production could contribute to the improvement of EPCs function by UTI treatment. Conclusions: UTI-induced phosphorylation/activation of eNOS and Akt, increases the intracellular level of NO, thereby improving tube formation and proliferation function of EPCs. EPCs function is crucial for re-endothelialization after denuding injuries of arteries