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1.
Patricio Atanes Inmaculada Ruz-Maldonado Ross Hawkes Bo Liu Min Zhao Guo Cai Huang Israa Mohammed Al-Amily Albert Salehi Stefan Amisten Shanta J. Persaud 《Cellular and molecular life sciences : CMLS》2018,75(16):3039-3050
Introduction
Islets synthesise and secrete numerous peptides, some of which are known to be important regulators of islet function and glucose homeostasis. In this study, we quantified mRNAs encoding all peptide ligands of islet G protein-coupled receptors (GPCRs) in isolated human and mouse islets and carried out in vitro islet hormone secretion studies to provide functional confirmation for the species-specific role of peptide YY (PYY) in mouse islets.Materials and methods
GPCR peptide ligand mRNAs in human and mouse islets were quantified by quantitative real-time PCR relative to the reference genes ACTB, GAPDH, PPIA, TBP and TFRC. The pathways connecting GPCR peptide ligands with their receptors were identified by manual searches in the PubMed, IUPHAR and Ingenuity databases. Distribution of PYY protein in mouse and human islets was determined by immunohistochemistry. Insulin, glucagon and somatostatin secretion from islets was measured by radioimmunoassay.Results
We have quantified GPCR peptide ligand mRNA expression in human and mouse islets and created specific signalomes mapping the pathways by which islet peptide ligands regulate human and mouse GPCR signalling. We also identified species-specific islet expression of several GPCR ligands. In particular, PYY mRNA levels were ~ 40,000-fold higher in mouse than human islets, suggesting a more important role of locally secreted Pyy in mouse islets. This was confirmed by IHC and functional experiments measuring insulin, glucagon and somatostatin secretion.Discussion
The detailed human and mouse islet GPCR peptide ligand atlases will allow accurate translation of mouse islet functional studies for the identification of GPCR/peptide signalling pathways relevant for human physiology, which may lead to novel treatment modalities of diabetes and metabolic disease.2.
Lei Chen Cong-Fa Huang Yi-Cun Li Wei-Wei Deng Liang Mao Lei Wu Wen-Feng Zhang Lu Zhang Zhi-Jun Sun 《Cellular and molecular life sciences : CMLS》2018,75(11):2045-2058
The NLRP3 inflammasome is a critical innate immune pathway responsible for producing active interleukin (IL)-1β, which is associated with tumor development and immunity. However, the mechanisms regulating the inflammatory microenvironment, tumorigenesis and tumor immunity are unclear. Herein, we show that the NLRP3 inflammasome was over-expressed in human HNSCC tissues and that the IL-1β concentration was increased in the peripheral blood of HNSCC patients. Additionally, elevated NLRP3 inflammasome levels were detected in tumor tissues of Tgfbr1/Pten 2cKO HNSCC mice, and elevated IL-1β levels were detected in the peripheral blood serum, spleen, draining lymph nodes and tumor tissues. Blocking NLRP3 inflammasome activation using MCC950 remarkably reduced IL-1β production in an HNSCC mouse model and reduced the numbers of myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs) and tumor-associated macrophages (TAMs). Moreover, inhibiting NLRP3 inflammasome activation increased the numbers of CD4+ and CD8+ T cells in HNSCC mice. Notably, the numbers of exhausted PD-1+ and Tim3+ T cells were significantly reduced. A human HNSCC tissue microarray showed that NLRP3 inflammasome expression was correlated with the expression of CD8 and CD4, the Treg marker Foxp3, the MDSC markers CD11b and CD33, and the TAM markers CD68 and CD163, PD-1 and Tim3. Overall, our results demonstrate that the NLRP3 inflammasome/IL-1β pathway promotes tumorigenesis in HNSCC and inactivation of this pathway delays tumor growth, accompanied by decreased immunosuppressive cell accumulation and an increased number of effector T cells. Thus, inhibition of the tumor microenvironment through the NLRP3 inflammasome/IL-1β pathway may provide a novel approach for HNSCC therapy. 相似文献
3.
This paper presents and discusses a simulation method for analyzing and evaluating system performance on a rail line from the perspective of speed profile. Dynamic analysis for train motions is introduced, and a discrete time-operation graph is proposed to represent the relation between speed profile and energy consumption. Based on them, an analytical model is formulated to provide a quick insight into the system performance. The discrete-time simulation (DTS) method is then implemented to study the system in detail. Compared to the existing simulations, two innovations are included in the DTS: (1) the analytical lookup tables that can simplify the dynamic computation and, (2) the speed profile adjustment process that forecasts and avoids future conflicts based on practical constraints. The numerical results show that the DTS speed profile has advantages over existing methods. Finally, the DTS method is used to analyze and evaluate the system performance of the current timetable on Beijing Yizhuang Metro Line. The results suggest that the current timetable is not robust enough, and thus possible improvements are discussed at both scheduling and operating stages. The proposed method is verified to be effective and reliable for practical uses. 相似文献
4.
Quantitative analysis has always been a difficult problem in security analysis of intrusion tolerance systems. An intrusion tolerance model based on multiple recovery mechanisms is introduced in this paper and how to quantify the security attributes of the model is proposed. A state transition model with recovery states more accurately describes the dynamic behavior of the system. Considering that recovery mechanisms have a great impact on the security performance of the system, we set up the cost models corresponding to different recovery mechanisms. We propose a feasible security measure based on mean cost to security failure in order to evaluate the system cost during the recovery phase. The experimental results confirmed the feasibility of the proposed methods. 相似文献
5.
Li-ying Huang Kuai-she Wang Wen Wang Kai Zhao Jie Yuan Ke Qiao Bing Zhang Jun Cai 《北京科技大学学报》2019,(2)
Low-carbon steel plates were successfully subjected to normal friction stir processing(NFSP) in air and submerged friction stir processing(SFSP) under water, and the microstructure, mechanical properties, and corrosion behavior of the NFSP and SFSP samples were investigated. Phase transformation and dynamic recrystallization resulted in fine-grained ferrite and martensite in the processed zone. The SFSP samples had smaller ferrites(5.1 μm), finer martensite laths(557 nm), and more uniform distribution of martensite compared to the NFSP samples. Compared to the base material(BM), the microhardness of the NFSP and SFSP samples increased by 19.8% and 27.1%, respectively because of the combined strengthening effects of grain refinement, phase transformation, and dislocation. The ultimate tensile strengths(UTSs) of the NFSP and SFSP samples increased by 27.1% and 38.7%, respectively. Grain refinement and martensite transformation also improved the electrochemical corrosion properties of the low-carbon steel. Overall, the SFSP samples had better mechanical properties and electrochemical corrosion resistance than the NFSP samples. 相似文献
6.
采用密度泛函理论中的CAM-B3LYP方法, 在6-31G(d)基组水平上优化气相条件下R型半胱氨酸(R-Cys)分子的几何构型, 理论研究电子激发过程中R-Cys体系片段间的电荷转移特征, 并基于弛豫与非弛豫激发态密度计算片段间的电荷转移百分数. 结果表明: 对于SH片段, S0到S3的电荷转移百分数为57.96%; 对于COOH片段, S0到S1~S5各激发态的电荷转移百分数均为负值, 二者电荷转移的定性结果一致; 对于NH2片段, S0到S1和S4的电荷转移百分数分别为6.98%和31.45%. 相似文献
7.
This paper studies the problem of primality testing for numbers of the form h · 2~n± 1,where h 2~n is odd, and n is a positive integer. The authors describe a Lucasian primality test for these numbers in certain cases, which runs in deterministic quasi-quadratic time. In particular, the authors construct a Lucasian primality test for numbers of the form 3 · 5 · 17 · 2~n± 1, where n is a positive integer, in half of the cases among the congruences of n modulo 12, by means of a Lucasian sequence with a suitable seed not depending on n. The methods of Bosma(1993), Berrizbeitia and Berry(2004), Deng and Huang(2016) can not test the primality of these numbers. 相似文献
8.
Monodispersed dihydrated zinc oxalate(ZnC_2O_4·2H_2O) particles with characteristic morphology were synthesized by aging a mixed solution of zinc nitrate(Zn(NO_3)_2) and sodium oxalate(Na_2C_2O_4) in the presence of a citrate ligand, with an average flat size of approximately 10–15 μm. The important parameters, including the solution pH values and the concentration of the zinc ions and citrate ligand, were investigated using a series of experiments. It is verified that the citrate ligand significantly affects the morphology of zinc oxalate particles, probably via its multiple roles of chelating, dispersing, and selective absorption. Thermodynamic equilibrium of the distribution of zinc species in an aqueous solution of Zn(Ⅱ)-citrate-oxalate-H_2O was estimated to explain the experimental results and to clarify the size and morphological evolution mechanism of the precipitated particles. 相似文献
9.
Journal of Systems Science and Complexity - This paper studies the estimation of the partially linear panel data models, allowing for cross-sectional dependence through a common factors structure.... 相似文献
10.
Journal of Systems Science and Complexity - The GVW algorithm is an efficient signature-based algorithm for computing Gröbner bases. In this paper, the authors consider the implementation of... 相似文献