47 research outputs found

    Macrophage deletion of Noc4l triggers endosomal TLR4/TRIF signal and leads to insulin resistance

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    In obesity, macrophages drive a low-grade systemic inflammation (LSI) and insulin resistance (IR). The ribosome biosynthesis protein NOC4 (NOC4) mediates 40 S ribosomal subunits synthesis in yeast. Hereby, we reported an unexpected location and function of NOC4L, which was preferentially expressed in human and mouse macrophages. NOC4L was decreased in both obese human and mice. The macrophage-specific deletion of Noc4l in mice displayed IR and LSI. Conversely, Noc4l overexpression by lentivirus treatment and transgenic mouse model improved glucose metabolism in mice. Importantly, we found that Noc4l can interact with TLR4 to inhibit its endocytosis and block the TRIF pathway, thereafter ameliorated LSI and IR in mice.Macrophage inflammation promotes insulin resistance during diet-induced obesity. Here the authors show that macrophage NOC4L is decreased in humans and mice with obesity, that macrophage NOC4L deficiency aggravated high-fat diet induced inflammation and insulin resistance, and that NOC4L interacts with toll-like receptor 4, to inhibit endocytosis, and thus blocks TLF4/TRIF inflammatory signaling

    Cyanidin-3-o-Glucoside Pharmacologically Inhibits Tumorigenesis via Estrogen Receptor β in Melanoma Mice

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    Expression patterns of estrogen receptors [ERα, ERβ, and G-protein associated ER (GPER)] in melanoma and skin may suggest their differential roles in carcinogenesis. Phytoestrogenic compound cyanidin-3-o-glucoside (C3G) has been shown to inhibit the growth and metastatic potential of melanoma, although the underlying molecular mechanism remains unclear. The aim of this study was to clarify the mechanism of action of C3G in melanoma in vitro and in vivo, as well as to characterize the functional expressions of ERs in melanoma. In normal skin or melanoma (n = 20/each), no ERα protein was detectable, whereas expression of ERβ was high in skin but weak focal or negative in melanoma; and finally high expression of GPER in all skin vs. 50% melanoma tissues (10/20) was found. These results correspond with our analysis of the melanoma survival rates (SRs) from Human Protein Atlas and The Cancer Genome Atlas GDC (362 patients), where low ERβ expression in melanoma correlate with a poor relapse-free survival, and no correlations were observed between SRs and ERα or GPER expression in melanoma. Furthermore, we demonstrated that C3G treatment arrested the cell cycle at the G2/M phase by targeting cyclin B1 (CCNB1) and promoted apoptosis via ERβ in both mouse and human melanoma cell lines, and inhibited melanoma cell growth in vivo. Our study suggested that C3G elicits an agonistic effect toward ERβ signaling enhancement, which may serve as a potential novel therapeutic and preventive approach for melanoma

    Transcriptional Activation of OsDERF1 in OsERF3 and OsAP2-39 Negatively Modulates Ethylene Synthesis and Drought Tolerance in Rice

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    The phytohormone ethylene is a key signaling molecule that regulates a variety of developmental processes and stress responses in plants. Transcriptional modulation is a pivotal process controlling ethylene synthesis, which further triggers the expression of stress-related genes and plant adaptation to stresses; however, it is unclear how this process is transcriptionally modulated in rice. In the present research, we report the transcriptional regulation of a novel rice ethylene response factor (ERF) in ethylene synthesis and drought tolerance. Through analysis of transcriptional data, one of the drought-responsive ERF genes, OsDERF1, was identified for its activation in response to drought, ethylene and abscisic acid. Transgenic plants overexpressing OsDERF1 (OE) led to reduced tolerance to drought stress in rice at seedling stage, while knockdown of OsDERF1 (RI) expression conferred enhanced tolerance at seedling and tillering stages. This regulation was supported by negative modulation in osmotic adjustment response. To elucidate the molecular basis of drought tolerance, we identified the target genes of OsDERF1 using the Affymetrix GeneChip, including the activation of cluster stress-related negative regulators such as ERF repressors. Biochemical and molecular approaches showed that OsDERF1 at least directly interacted with the GCC box in the promoters of ERF repressors OsERF3 and OsAP2-39. Further investigations showed that OE seedlings had reduced expression (while RI lines showed enhanced expression) of ethylene synthesis genes, thereby resulting in changes in ethylene production. Moreover, overexpression of OsERF3/OsAP2-39 suppressed ethylene synthesis. In addition, application of ACC recovered the drought-sensitive phenotype in the lines overexpressing OsERF3, showing that ethylene production contributed to drought response in rice. Thus our data reveal that a novel ERF transcriptional cascade modulates drought response through controlling the ethylene synthesis, deepening our understanding of the regulation of ERF proteins in ethylene related drought response

    The Research of the Tang Princesses' Family Life

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    郭海文,陕西师范大学历史文化学院副教授,主要致力于中国古代史、性别史研究。【中文摘要】过去的历史研究,太过忽略女性,以至建构出来的历史图像有很大的缺陷。在传统中国,家庭是绝大多数妇女唯一可能有深度参与的生活领域,对了解过往的女性而言,家庭史的研究具有重要性。本文对大唐公主的家庭生活从公主与娘家血肉相连的关系、公主在夫家的人际网络——以与舅姑关系为中心、公主驸马的相处之道、为人母之道——生育与母子亲情等方面加以系统阐释,以期勾勒出公主的家庭生活场景及生存空间。 【Abstract】During the past time, we have always ignored women in historical research, which has resulted in there were a lot of deficiencies in the construction of historical images. In traditional China, family might be the only place where the great majority of women have taken part in deeply. Studying family history makes a big influence on learning about women. This paper hackles Tang princesses' family life, which is divided into four parts. First, introduce the relationship between a princess and her family. Second, the relationship between the princess and her parents-in-law locates in the center of the princess's interpersonal network in her husband's family. Third, how the princess went along with her husband. Fourth, giving birth to her children and the affection between the princess and their children is the princess's maternity. By analyzing the four aspects of Tang princesses’ family life,we can outline the princess’s family life scenes and living space.本文为2015年国家社科基金后期资助项目“大唐公主命运图谱”(15FZS037)阶段性成果

    DYNAMICS SIMULATION OF WDP LOADING DEVICE ON THE REDUCER TEST BED OF SCRAPER CONVEYOR

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    The purpose is to design suitable loading test devices for small and medium-sized reducer manufacturing enterprises with the characteristics of low cost,energy saving and torque exerting dynamically. It designed the loading devices of"worm control and double planetary transmission"on the basis of the design and rationality analysis of the test bed of mechanical sealing scraper conveyor retarders. It set the parameters of the actual overload test for the simulation and carried out the dynamic simulation on the loading device and determined the performance relationship. It provides a new loading method of reducer test bed for the small and medium-sized manufacturing enterprises

    Influence of softening annealing on microstructural heredity and mechanical properties of medium-Mn steel

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    Softening annealing (SA) is often required for producing medium-Mn steels (MMS) as it lowers hardness so that they can be cold rolled to reduce thickness. The influences of different SA processes on the microstructural heredity during the processing route and the final tensile properties were studied. It was found that the SA process could either intensify or weaken the influence of the Mn segregation resulting from solidification on the subsequent microstructural evolution during the process, i.e., microstructural heredity. In the case when no SA was employed, both recrystallization and rapid growth of ferrite grains preceded the reverse austenitic transformation during the intercritical annealing (IA) in the Mn-lean regions, where very coarse ferrite grains were formed. This deteriorated ductility due to the propagation of cracking along the boundary of the coarse-grained and fine-grained regions. In contrast, SA at a sufficiently high temperature could dissolve cementite, producing uniformly distributed austenite grains. They transformed to martensite during cold rolling but were reborn during IA. As a result, ultrafine austenite and ferrite grains were uniformly distributed, which improved ductility significantly. This study hints at a new approach to altering the microstructural heredity resulting from the heterogeneous Mn distribution in MMS

    Strong Plasmon-Mie Resonance in Si@Pd Core-Ω Shell Nanocavity

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    The surface plasmon resonance (SPR) and localized surface plasmon resonance (LSPR) can be used to enhance the generation of the hot electrons in plasmon metal nanocavity. In this paper, Pd nanomembrane (NMB) is sputtered on the surface of Si nanosphere (NS) on glass substrate to form the Si@Pd core-Ω shell nanocavity. A plasmon-Mie resonance is induced in the nanocavity by coupling the plasmon resonance with the Mie resonance to control the optical property of Si NS. When this nanocavity is excited by near-infrared-1 (NIR-1, 650 nm–900 nm) femtosecond (fs) laser, the luminescence intensity of Si NS is dramatically enhanced due to the synergistic interaction of plasmon and Mie resonance. The generation of resonance coupling regulates resonant mode of the nanocavity to realize multi-dimensional nonlinear optical response, which can be utilized in the fields of biological imaging and nanoscale light source

    Strong Plasmon-Mie Resonance in Si@Pd Core-Ω Shell Nanocavity

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    The surface plasmon resonance (SPR) and localized surface plasmon resonance (LSPR) can be used to enhance the generation of the hot electrons in plasmon metal nanocavity. In this paper, Pd nanomembrane (NMB) is sputtered on the surface of Si nanosphere (NS) on glass substrate to form the Si@Pd core-Ω shell nanocavity. A plasmon-Mie resonance is induced in the nanocavity by coupling the plasmon resonance with the Mie resonance to control the optical property of Si NS. When this nanocavity is excited by near-infrared-1 (NIR-1, 650 nm–900 nm) femtosecond (fs) laser, the luminescence intensity of Si NS is dramatically enhanced due to the synergistic interaction of plasmon and Mie resonance. The generation of resonance coupling regulates resonant mode of the nanocavity to realize multi-dimensional nonlinear optical response, which can be utilized in the fields of biological imaging and nanoscale light source
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