Serine 58 of 14-3-3ζ Is a molecular switch regulating ASK1 and oxidant stress-induced cell death

Oxidant stress is a ubiquitous stressor with negative impacts on multiple cell types. ASK1 is a central mediator of oxidant injury, but while mechanisms of its inhibition, such as sequestration by 14-3-3 proteins and thioredoxin, have been identified, mechanisms of activation have remained obscure and the signaling pathways regulating this are not clear. Here, we report that phosphorylation of 14-3-3ζ at serine 58 (S58) is dynamically regulated in the cell and that the phosphorylation status of S58 is a critical factor regulating oxidant stress-induced cell death. Phosphorylation of S58 releases ASK1 from 14-3-3ζ, and ASK1 then activates stress-activated protein kinases, leading to cell death. While several members of the mammalian sterile 20 (Mst) family of kinases can phosphorylate S58 when overexpressed, we identify Ste20/oxidant stress response kinase 1 (SOK-1), an Mst family member known to be activated by oxidant stress, as a central endogenous regulator of S58 phosphorylation and thereby of ASK1-mediated cell death. Our findings identify a novel pathway that regulates ASK1 activation and oxidant stress-induced cell death

Tool path planning based on conformal parameterization for meshes

AbstractThe similarity property of conformal parameterization makes it able to locally preserve the shapes between a surface and its parameter domain, as opposed to common parameterization methods. A parametric tool path planning method is proposed in this paper through such parameterization of triangular meshes which is furthermore based on the geodesic on meshes. The parameterization has the properties of local similarity and free boundary which are exploited to simplify the formulas for computing path parameters, which play a fundamentally important role in tool path planning, and keep the path boundary-conformed and smooth. Experimental results are given to illustrate the effectiveness of the proposed methods, as well as the error analysis

Different Genetic Resistance Resulted in Distinct Response to Newcastle Disease Virus

As one of the most severe infectious diseases in the poultry industry, Newcastle disease (ND) causesa significant economic loss worldwideeven with the extensive implementation of vaccine. Tofind targets to improvegenetic resistance to NDto enhanceprotection in chickens, gene expression was analyzedin spleen of two chickenlines which differed in their resistanceto ND. The comparison of gene expression between two treatments(challenged or non-challenged)inthe two chicken lines at 2 and 6 days post-inoculation (dpi) suggeststhat thatt he mostdramatic changes ofgene expression occurredin Leghorn chickens at 2dpi.Theidentifieddifferentially expressed genesthat regulatesplenicresponse toNDVprovidepotential avenuestobreedNDV-resistantchickens in the future

Degradation of Toxic Organic Contaminants by Graphene Cathode in an Electro‐Fenton System

A novel composite electrode was constructed by pressing graphene and CuO, using a cathode in an electro‐Fenton (EF) system. Cyclic voltammetry, charge/discharge curve and electrochemical impedance spectroscopy (EIS) were used to characterize the composite electrode. The degradation of a toxic organic contaminant, Terramycin, by EF system was studied in an undivided electrolysis cell. The possible degradation products of Terramycin were studied by a Fourier transform‐infrared spectrum, and the findings showed that the structure of Terramycin was damaged. The variations of hydrogen peroxide and the relative content of hydroxyl radical (.OH) during the degradation process were traced by enzyme catalysis method and fluorescence spectrometry. The results showed that the electro‐catalytic degradation of Terramycin occurred by an ·OH radical mechanism. More importantly, this as‐prepared cathode was very stable and could be reused without any catalytic activity decrease, suggesting its potential application in the wastewater treatment

Transcriptome Analysis in Spleen Reveals Differential Regulation of Response to Newcastle Disease Virus in Two Chicken Lines.

Enhancing genetic resistance of chickens to Newcastle Disease Virus (NDV) provides a promising way to improve poultry health, and to alleviate poverty and food insecurity in developing countries. In this study, two inbred chicken lines with different responses to NDV, Fayoumi and Leghorn, were challenged with LaSota NDV strain at 21 days of age. Through transcriptome analysis, gene expression in spleen at 2 and 6 days post-inoculation was compared between NDV-infected and control groups, as well as between chicken lines. At a false discovery rate <0.05, Fayoumi chickens, which are relatively more resistant to NDV, showed fewer differentially expressed genes (DEGs) than Leghorn chickens. Several interferon-stimulated genes were identified as important DEGs regulating immune response to NDV in chicken. Pathways predicted by IPA analysis, such as "EIF-signaling", "actin cytoskeleton organization nitric oxide production" and "coagulation system" may contribute to resistance to NDV in Fayoumi chickens. The identified DEGs and predicted pathways may contribute to differential responses to NDV between the two chicken lines and provide potential targets for breeding chickens that are more resistant to NDV

The role of mesenchymal stem cells derived exosomes as a novel nanobiotechnology target in the diagnosis and treatment of cancer

Mesenchymal stem cells (MSCs), one of the most common types of stem cells, are involved in the modulation of the tumor microenvironment (TME). With the advancement of nanotechnology, exosomes, especially exosomes secreted by MSCs, have been found to play an important role in the initiation and development of tumors. In recent years, nanobiotechnology and bioengineering technology have been gradually developed to detect and identify exosomes for diagnosis and modify exosomes for tumor treatment. Several novel therapeutic strategies bioengineer exosomes to carry drugs, proteins, and RNAs, and further deliver their encapsulated cargoes to cancer cells through the properties of exosomes. The unique properties of exosomes in cancer treatment include targeting, low immunogenicity, flexibility in modification, and high biological barrier permeability. Nevertheless, the current comprehensive understanding of the roles of MSCs and their secreted exosomes in cancer development remain inadequate. It is necessary to better understand/update the mechanism of action of MSCs-secreted exosomes in cancer development, providing insights for better modification of exosomes through bioengineering technology and nanobiotechnology. Therefore, this review focuses on the role of MSCs-secreted exosomes and bioengineered exosomes in the development, progression, diagnosis, and treatment of cancer

GSK-3alpha directly regulates beta-adrenergic signaling and the response of the heart to hemodynamic stress in mice.

The glycogen synthase kinase-3 (GSK-3) family of serine/threonine kinases consists of 2 highly related isoforms, alpha and beta. Although GSK-3beta has an important role in cardiac development, much remains unknown about the function of either GSK-3 isoform in the postnatal heart. Herein, we present what we believe to be the first studies defining the role of GSK-3alpha in the mouse heart using gene targeting. Gsk3a(-/-) mice over 2 months of age developed progressive cardiomyocyte and cardiac hypertrophy and contractile dysfunction. Following thoracic aortic constriction in young mice, we observed enhanced hypertrophy that rapidly transitioned to ventricular dilatation and contractile dysfunction. Surprisingly, markedly impaired beta-adrenergic responsiveness was found at both the organ and cellular level. This phenotype was reproduced by acute treatment of WT cardiomyocytes with a small molecule GSK-3 inhibitor, confirming that the response was not due to a chronic adaptation to LV dysfunction. Thus, GSK-3alpha appears to be the central regulator of a striking range of essential processes, including acute and direct positive regulation of beta-adrenergic responsiveness. In the absence of GSK-3alpha, the heart cannot respond effectively to hemodynamic stress and rapidly fails. Our findings identify what we believe to be a new paradigm of regulation of beta-adrenergic signaling and raise concerns given the rapid expansion of drug development targeting GSK-3

Transcriptome analysis reveals inhibitory effects of lentogenic Newcastle disease virus on cell survival and immune function in spleen of commercial layer chicks

As a major infectious disease in chickens, Newcastle disease causes considerable economic losses in the poultry industry, especially in developing countries where there is limited access to effective vaccination. Therefore, enhancing resistance to the virus in commercial chickens through breeding is a promising way to promote poultry production. In this study, we investigated gene expression changes at 2 and 6 dpi after infection at day21 with a lentogenic Newcastle disease virus in a commercial egg-laying chicken hybrid using RNA sequencing analysis. By comparing NDV challenged and nonchallenged groups, 526 differentially expressed genes (DEGs) (FDR \u3c 0.05) were identified at 2 dpi, and only 36 at 6 dpi. For the DEGs at 2 dpi, IPA analysis predicted inhibition of multiple signaling pathways in response to NDV that regulate immune cell development and activity, neurogenesis and angiogenesis. Upregulation of Interferon Induced Protein with Tetratricopeptide Repeats 5 (IFIT5) in response to NDV was consistent between the current and most previous studies. Sprouty RTK Signaling Antagonist 1 (SPRY1), a DEG in the current study is located in a significant QTL associated with virus load at 6 dpi in the same population. These identified pathways and DEGs provide potential targets to further study breeding strategy to enhance NDV resistance in chickens

Artificial local magnetic field inhomogeneity enhances T2 relaxivity

磁性探针作为分子影像技术中的磁共振成像（MRI）造影剂在医学诊断中发挥着重要作用。为满足实际诊断中的准确性和精确性要求，科研工作者们长期致力于发展高性能的MRI造影剂以降低高剂量的使用带来的潜在风险。该文章指出了探针聚集体中局域磁场不均匀性是影响T2弛豫效能的关键因素。该文章首次利用磁场不均匀性因素阐明了单个探针和它们聚集体的MRI造影剂之间的相互关系，将可能成为弥补探针聚集体的造影剂理论的空白，并为发展新型高效的MRI造影剂提供重要参考。 该论文共同第一作者为博士后周子健和博士生田蕊，通讯作者为陈小元教授和聂立铭博士，部分工作得到我校物理学系王瑞方教授和化学化工学院高锦豪教授的支持。【Abstract】Clustering of magnetic nanoparticles (MNPs) is perhaps the most effective, yet intriguing strategy to enhance T2 relaxivity in magnetic resonance imaging (MRI). However, the underlying mechanism is still not fully understood and the attempts to generalize the classic outersphere theory from single particles to clusters have been found to be inadequate. Here we show that clustering of MNPs enhances local field inhomogeneity due to reduced field symmetry, which can be further elevated by artificially involving iron oxide NPs with heterogeneous geometries in terms of size and shape. The r2 values of iron oxide clusters and Landau–Lifshitz–Gilbert simulations confirmed our hypothesis, indicating that solving magnetic field inhomogeneity may become a powerful way to build correlation between magnetization and T2 relaxivity of MNPs, especially magnetic clusters. This study provides a simple yet distinct mechanism to interpret T2 relaxivity of MNPs, which is crucial to the design of high-performance MRI contrast agents.This work was supported by the National Science Foundation of China (81571744 and 81601489), the National Basic Research Program of China (863 Program 2015AA020502), the Fundamental Research Funds for the Central Universities (20720170065), the Science Foundation of Fujian Province (No. 2014Y2004), and by the Intramural Research Program (IRP), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). 研究工作得到了国家自然科学基金委、国家高技术研究发展计划863项目、福建省重大研发平台项目和美国NIH Intramural Research Program的资助

Artificial local magnetic field inhomogeneity enhances T2 relaxivity

磁性探针作为分子影像技术中的磁共振成像（MRI）造影剂在医学诊断中发挥着重要作用。为满足实际诊断中的准确性和精确性要求，科研工作者们长期致力于发展高性能的MRI造影剂以降低高剂量的使用带来的潜在风险。该文章指出了探针聚集体中局域磁场不均匀性是影响T2弛豫效能的关键因素。该文章首次利用磁场不均匀性因素阐明了单个探针和它们聚集体的MRI造影剂之间的相互关系，将可能成为弥补探针聚集体的造影剂理论的空白，并为发展新型高效的MRI造影剂提供重要参考。 该论文共同第一作者为博士后周子健和博士生田蕊，通讯作者为陈小元教授和聂立铭博士，部分工作得到我校物理学系王瑞方教授和化学化工学院高锦豪教授的支持。【Abstract】Clustering of magnetic nanoparticles (MNPs) is perhaps the most effective, yet intriguing strategy to enhance T2 relaxivity in magnetic resonance imaging (MRI). However, the underlying mechanism is still not fully understood and the attempts to generalize the classic outersphere theory from single particles to clusters have been found to be inadequate. Here we show that clustering of MNPs enhances local field inhomogeneity due to reduced field symmetry, which can be further elevated by artificially involving iron oxide NPs with heterogeneous geometries in terms of size and shape. The r2 values of iron oxide clusters and Landau–Lifshitz–Gilbert simulations confirmed our hypothesis, indicating that solving magnetic field inhomogeneity may become a powerful way to build correlation between magnetization and T2 relaxivity of MNPs, especially magnetic clusters. This study provides a simple yet distinct mechanism to interpret T2 relaxivity of MNPs, which is crucial to the design of high-performance MRI contrast agents.This work was supported by the National Science Foundation of China (81571744 and 81601489), the National Basic Research Program of China (863 Program 2015AA020502), the Fundamental Research Funds for the Central Universities (20720170065), the Science Foundation of Fujian Province (No. 2014Y2004), and by the Intramural Research Program (IRP), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). 研究工作得到了国家自然科学基金委、国家高技术研究发展计划863项目、福建省重大研发平台项目和美国NIH Intramural Research Program的资助