关键词： attention-deficit hyperactivity disorder   brain   organophosphate   endocannabinoid   spontaneously hypertensive rat  

摘要： Anticholinergic organophosphate (OP) agents act on the diverse serine hydrolases, thereby revealing unexpected biological effects. Epidemiological studies indicate a relationship between the OP exposure and development of attention -deficit/hyperactivity disorder (ADHD)-like symptoms, whereas no plausible mechanism for the OP-induced ADHD has been established. The present investigation employs ethyl octylphosphonofluoridate (EOPF) as an OP-probe, which is an extremely potent inhibitor of endocannabinoid (EC, anandamide and 2-arachidonoylglycerol)-hydrolyzing enzymes: that is, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). An ex vivo experiment shows that EOPF treatment decreases FAAH and MAGL activities and conversely increases EC levels in the rat brain. Subsequently, EOPF (treated intraperitoneally once at 0, 1, 2, or 3 mg/kg) clearly induces ADHD-like behaviors (in elevated plus-maze test) in both Wistar and spontaneously hypertensive rats. The EOPF-induced behaviors are reduced by a concomitant administration of cannabinoid receptor inverse agonist SLV-319. Accordingly, the EC system is a feasible target for OP-caused ADHD-like behaviors in adolescent rats.

关键词： Artificial sex change   Protogynous grouper   Seasonal sex change   Steroids   Social control   Social unit size  

摘要： In this study, a highly efficient method of inducing sex change using social control in the protogynous orange-spotted grouper (Epinephelus coioides) was developed. A series of experiments were carried out to investigate the influence of social unit size and seasonality on the rate of sex change rate in the orange-spotted grouper. The results revealed that the removal of male fish in social units with three females during the pre-breeding and breeding seasons was the fastest method ever recorded for inducing an artificial sex change in orange-spotted grouper. The data indicated that a sex change generally occurred in the largest female in the social unit. A sharp increase in levels of androgen and cortisol in serum are proposed as a marker of the onset of a female-to-male sex change. Using the method described in this study, a sex change from female to male occurred within two to four weeks of removing males from the social unit. To examine sperm fertility, the fertilization rate of males obtained by induced sex change was analyzed. The results revealed that males obtained by this method can successfully fertilize mature eggs. This method could address the scarcity of male groupers required for spawning in captivity, and would promote the development of grouper aquaculture.

关键词： GPR173   Phoenixin-20   Lipopolysaccharide (LPS)   Inflammation   Human dental pulp cells (hDPCs)  

摘要： Pulpal infection is one of the most common causes of dental emergency admission. Tooth pain due to infection caused by gram-negative bacteria is the main manifestation of this sort of dental problem. The GPR173 signaling pathway is a highly conserved G-protein-coupled receptor that mediates neurological and reproductive function. In this study, we found that GPR173 was fairly expressed in isolated human dental pulp cells, and its expression was reduced in response to pro-inflammatory lipopolysaccharide (LPS) treatment. The activation of GPR173 by its ligand Phoenixin-20 reduced LPS-induced cytotoxicity, as revealed by a reduction in the release of LDH. Additionally, Phoenixin-20 suppressed LPS-induced release of pro-inflammatory cytokines and inflammatory mediators, including IL-6, MCP-1, VCAM-1, and ICAM-1, as well as MMP-2 and MMP-9. Mechanistically, we showed the suppressive action of Phoenixin-20 on LPS-induced activation of TLR-4 and Myd88 as well as the activation of the NF-kappa B pathway. Collectively, our study demonstrates that the GPR173 signaling pathway is an important mediator of LPS-induced inflammation, and the activation of GPR173 by its natural ligand Phoenixin-20 exhibits robust anti-inflammatory effects in dental pulp cells, suggesting that GPR173 is an interesting target molecule in the development of pulp cell-based therapies.

摘要： Reactive oxygen species (ROS) inflict multiple types of lesions in DNA, threatening genomic integrity. How cells respond to ROS-induced DNA damage at telomeres is still largely unknown. Here, we show that ROS-induced DNA damage at telomeres triggers R-loop accumulation in a TERRA- and TRF2-dependent manner. Both ROS-induced single- and double-strand DNA breaks (SSBs and DSBs) contribute to R-loop induction, promoting the localization of CSB and RAD52 to damaged telomeres. RAD52 is recruited to telomeric R-loops through its interactions with both CSB and DNA:RNA hybrids. Both CSB and RAD52 are required for the efficient repair of ROS-induced telomeric DSBs. The function of RAD52 in telomere repair is dependent on its ability to bind and recruit POLD3, a protein critical for break-induced DNA replication (BIR). Thus, ROS-induced telomeric R-loops promote repair of telomeric DSBs through CSB-RAD52-POLD3-mediated BIR, a previously unknown pathway protecting telomeres from ROS. ROS-induced telomeric SSBs may not only give rise to DSBs indirectly, but also promote DSB repair by inducing R-loops, revealing an unexpected interplay between distinct ROS-induced DNA lesions.

关键词： Interleukin 6   Histone acetylation   Epigenetics   HDAC1/2  

摘要： Interleukin 6 (IL-6) is a major proinflammatory cytokine involved in several aspects of the immune response. Excessive IL-6 production and dysregulated IL-6 receptor signaling lead to multiple inflammatory and autoimmune diseases, such as asthma, even cancer. Thus, its precise regulatory mechanisms need to be fully addressed. Here we found that knockdown of protein C-ets-2 (Ets2) resulted in higher IL-6 production after TLRs activation in macrophages. Mechanistically, Ets2 associated with an epigenetic modifier histone deacetylase 1 (HDAC1) and promoted its recruitment to the Il6 promoter after TLRs activation. Subsequentially, it enhanced histone deacetylation and inhibited Il6 mRNA transcription. Thus, Ets2 epigenetically suppresses TLRs-induced IL-6 production in both human and murine macrophages via promoting histone deacetylation of the Il6 promoter, serving as a new potential therapeutic target in inflammatory diseases therapy. (C) 2019 Elsevier Inc. All rights reserved.

关键词： Breast cancer   Apoptosis   Microtubule destabilization   Topoisomerase   Molecular docking studies   Acute oral toxicity  

摘要： Breast cancer is the second leading cause of deaths in women globally. Present communication deals with design and synthesis of a few diarylnaphthyls as possible anti-breast cancer agents. Among the thirty three representatives with significant antiproliferative activity compounds 23 and 50 were quite efficacious against human breast cancer cells. Compound 50 induced apoptosis in both MCF-7 and MDA-MB-231 cells and exerted S phase and G2/M phase arrest respectively via distinct mechanistic pathways. It showed moderate microtubule destabilization. Further, it exhibited DNA topoisomerase-II inhibition effect in MCF-7 cells. It was well tolerable and found safe up to 300 mg/kg dose in Swiss albino mice. The dual action antiproliferative effect of compound 50 is quite interesting and warrants for future development. (C) 2019 Elsevier Masson SAS. All rights reserved.

关键词： Circular RNA   Adipogenic differentiation   Metabolic syndrome   Human adipose-derived stem cells   Polypyrimidine tract-binding protein 1   Sterol-regulatory element binding proteins  

摘要： Purpose: The metabolic syndrome (MetS) is characterized of a cluster of medical disorders. Altered function of adipose tissue has a significant impact on whole-body metabolism and represents a key driver for MetS. In this study, we aim to explore the function of human circular RNA H19 (hsa_circH19) in human adipose-derived stem cells (hADSCs). Methods: The blood samples from MetS patients and normal subjects were used to determine the expression level of the hsa_circH19. After knock-down of hsa_circH19 in hADSCs, we measured the expression of adipogenic genes. Oil red 0, Nile red staining assay and triglyceride assessment were performed to examine the role of hsa_circH19 in hADSCs differentiation. Then, RNA Pull-down and RIP assays were conducted to explore the related RNA binding protein of hsa_circH19. IF was performed to determine the potential molecular regulatory mechanism. Results: After accounting for confounding factors, high levels of hsa_circH19 remained an independent risk factor for MetS. Furthermore, the knockdown of hsa_circH19 significantly increased the expression of adipogenic genes and the formation of lipid droplets. Bioinformatics analyses revealed that has_circH19 shared multiple binding sites with polypyrimidine tract-binding protein 1 (PTBP1) and their interaction was validated by circRNA pull-down and RIP assays. Mechanistically, depletion of hsa_circH19 triggered translocation of sterol-regulatory element binding proteins (SREBP1) from cytoplasm to nucleus in the presence of PTBP1. Conclusion: Our experiments suggest that knockdown of hsa_circH19 promotes hADCSs adipogenic differentiation via targeting of PTBP1. Inconsequence, the expression of hsa_circH19 might correlated to lipid metabolism in adipose tissue from MetS.

关键词： Ti-6Al-4V   Grain size   Crystallographic texture   Sliding mechanism   Slip traces   Critical resolved shear stress (CRSS)  

摘要： The aim of this paper is to investigate the coupled effects of grain size and crystallographic texture on the mechanical behavior induced by gliding mechanism in Ti-6Al-4V alloy. Thus, four microstructures of Ti-6Al-4V alloy whose grain size and crystallographic texture are different were examined by tensile tests along the rolling direction at room temperature. In this study, the contribution of gliding on basal < a >, prismatic < a > and pyramidal < c + a > plans in the accommodation of plastic strain was estimated by means of a slip trace analysis. The role of the individual grain size and the crystallographic texture was then statistically evaluated. Based on the results of slip trace analysis, numerical optimizations of the Critical Resolved Shear Stress < CRSS > of basal < a >, prismatic < a > and pyramidal < c + a > in the four microstructures were then carried out, using transition scale rules and a local behavior model. The results suggest that the mechanical behavior of Ti-6Al-4V is controlled by the activation of slip systems that depend not only on their CRSS but also the initial orientation and size of each individual grain. The low CRSS of prismatic < a > slip systems can lead to early activation of these systems in favorably oriented coarse grains. Therefore, a local plastic deformation can be shown. At high levels of loading, increasing the grain size can minimize the crystallographic texture effects by deforming the unfavorably oriented coarse grains. Moreover, based on the results of the numerical optimization, it can be also suggested that the CRSS can decrease with the increase in grain size according to the local Hall Petch relationship.

关键词： Radiation   Sarcoma   Endoplasmic reticulum stress   Autophagy   Apoptosis  

摘要： Endoplasmic reticulum (ER) stress is a conserved cellular process for cells to clear unfolded or misfolded proteins and maintain cell homeostasis under stress conditions. Autophagy may act as a pro-survival strategy to cope with multiple stress conditions in tumor progression and distant metastasis. Although many studies have demonstrated that there is a close correlation between radiation-induced ER stress and autophagy, the molecular mechanisms currently remain unclear. In the present study, we performed an in vivo study concerning the effect of autophagy induced by ER stress on the radio-sensitivity of mouse sarcoma using X-rays. Our results documented that X-rays could induce ER stress in sarcoma and then autophagy was activated by unfolded protein response (UPR) through the IRE1-JNK-pBcl2-Beclin1 signaling axis. The induction of autophagy caused a decline in cell apoptosis while inhibiting the autophagy resulted in increased apoptosis and inhibition of tumor progression. Combined treatment of X-ray exposure and chloroquine increased ER stress-related apoptosis and enhanced the radiosensitivity of mouse sarcoma that was not sensitive to X-ray irradiation alone. Thus, our study indicates that inhibition of ER stress-induced autophagy might be a novel strategy to improve the efficacy of radiotherapy against radioresistant sarcoma. (C) 2019 Elsevier Inc. All rights reserved.

关键词： 北斗导航系统   无人机   应用  

摘要： 作为一种更加科学的运营模式,无人机在我国战斗机、工业方面的发展过程中发挥着极其重要的作用。随着中国北斗导航系统的不断改进和完善,在北斗导航系统基础上的无人机导航系统为我国战斗机、工业、农业方面的信息安全提供了一定的技术支持。通过对这项系统以及其在战斗机、工业、农业方面中的应用分析,希望可以发现在现阶段应用中所存在的问题,并提出科学有效的解决方案以及措施,以提高无人机应用中的发展水平。