Increased circulating circular RNA103516 is a novel biomarker for inflammatory bowel disease in adult patients

BACKGROUND Increasing evidence demonstrates that by acting as microRNA sponges modulating gene expression at the transcriptional or post-transcriptional level,circular RNAs(circRNAs)participate in the pathogenesis of a variety of diseases and are considered ideal biomarkers of human disease.AIM To examine the expression of circRNA_103516 in inflammatory bowel disease(IBD)and its associations with clinical phenotypes and inflammatory cytokines.METHODS Peripheral blood mononuclear cells(PBMCs)were obtained from patients with IBD,healthy controls(HCs),and patient controls(PCs).Expression of circRNA_103516 and hsa-miR-19b-1-5p was assessed by quantitative reverse transcription-polymerase chain reaction.Crohn's disease activity index(CDAI),Mayo score,C-reactive protein(CRP)level,and erythrocyte sedimentation rate(ESR)were measured.To assess the inflammatory cytokines tumour necrosis factorα(TNF-α),interferon-γ(IFN-γ),and interleukin-10(IL-10),blood samples were analysed by flow cytometry.RESULTS Ninety Crohn’s disease(CD)and 90 ulcerative colitis(UC)patients,80 HCs,and 35 PCs were included in the study.CircRNA_103516 was upregulated in CD and UC patients compared with HCs and PCs(P<0.05).The area under the curve of circRNA_103516 for diagnosing CD and UC was 0.790 and 0.687,respectively.In addition,circRNA_103516 levels were increased in active CD and UC compared with remittent groups(P=0.027,P=0.045).Furthermore,in CD,circRNA_103516 correlated positively with CDAI(P<0.001),CRP(P<0.001),ESR(P<0.001),TNFα(P<0.001),and IFN-γ(P<0.001)and negatively correlated with IL-10(P=0.006).In UC patients,circRNA_103516 correlated with Mayo score(P<0.001),CRP(P<0.001),ESR(P<0.001),TNFα(P<0.001),IFN-γ(P=0.011),and IL-10(P=0.002).Additionally,circRNA_103516 correlated positively with stricturing(P=0.018)and penetrating(P=0.031)behaviour.Moreover,hsamiR-19b-1-5p correlated negatively with circRNA_103516 in CD.CONCLUSION CircRNA_103516 levels in PBMCs can be considered an ideal candidate biomarker for diagnosing IBD.Dysregulation of circRNA_103516 may participate in the molecular mechanism of IBD through hsa-miR-19b-1-5p sponging.

Hsa_circRNA_102610 upregulation in Crohn’s disease promotes transforming growth factor-β1-induced epithelial-mesenchymal transition via sponging of hsa-miR-130a-3p

BACKGROUND The incidence of inflammatory bowel disease,a chronic intestinal inflammatory disorder that includes Crohn’s disease(CD)and ulcerative colitis,is rising.Circular RNAs are considered valuable diagnostic biomarkers for CD.Current evidence supports the views that epithelial-mesenchymal transition(EMT)plays an important role in CD pathogenesis,and that hsa-miR-130a-3p can inhibit transforming growth factor-β1(TGF-β1)-induced EMT.Our previous study revealed that hsa_circRNA_102610 was upregulated in CD patients.Moreover,we predicted an interaction between hsa_circRNA_102610 and hsa-miR-130a-3p.Thus,we hypothesized that hsa_circRNA_102610 may play roles in the proliferation and EMT of intestinal epithelial cells by sponging hsa-miR-130a-3p to participate in the pathogenesis of CD.AIM To explore the mechanism of hsa_circRNA_102610 in the pathogenesis of CD.METHODS The relative expression levels of hsa_circRNA_102610 and hsa-miR-130a-3p in patients were detected by quantitative reverse transcription-polymerase chain reaction.The proliferation of human intestinal epithelial cells(HIECs)and normal-derived colon mucosa cell line 460(NCM460)cells was detected by cell counting kit-8,5-ethynyl-2’-deoxyuridine staining and cell cycle assays following overexpression or downregulation of hsa_circRNA_102610.Cell proliferation assays were performed as described above in a rescue experiment with hsa-miR-130a-3p mimics.The interaction of hsa_circRNA_102610 and hsa-miR-130a-3p was verified by fluorescence in situ hybridization and dual luciferase reporter assays.The relative expression levels of CyclinD1,mothers against decapentaplegic homolog 4(SMAD4),E-cadherin,N-cadherin and Vimentin were detected by western blotting following hsa_circRNA_102610 overexpression,TGF-β1-induced EMT or hsa-miR-130a-3p mimic transfection(in rescue experiments).RESULTS Upregulation of hsa_circRNA_102610 was determined to be positively correlated with elevated fecal calprotectin levels in CD(r=0.359,P=0.007)by Pearson correlation analysis.Hsa_circRNA_102610 promoted the proliferation of HIECs and NCM460 cells,while hsa-miR-130a-3p reversed the cell proliferationpromoting effects of hsa_circRNA_102610.Fluorescence in situ hybridization and dual luciferase reporter assays showed that hsa_circRNA_102610 directly bound hsa-miR-130a-3p in NCM460 and 293T cells.An inverse correlation between downregulation of hsa-miR-130a-3p and upregulation of hsa_circRNA_102610 in CD patients was observed(r=-0.290,P=0.024)by Pearson correlation analysis.Moreover,overexpression of hsa_circRNA_102610 promoted SMAD4 and CyclinD1 protein expression validated by western-blotting.Furthermore,overexpression of hsa_circRNA_102610 promoted TGF-β1 induced EMT in HIECs and NCM460 cells via targeting of hsa-miR-130a-3p,with increased expression of Vimentin and N-cadherin and decreased expression of E-cadherin.CONCLUSION Hsa_circRNA_102610 upregulation in CD patients could promote the proliferation and EMT of intestinal epithelial cells via sponging of hsa-miR-130a-3p.

Measurement of atmospheric non-reciprocity effects for satellite-based two-way time-frequency transfer

Future optical clock networks will require high-precision optical time-frequency transfer between satellites and ground stations.However,due to atmospheric turbulence,satellite motion and time delay between the satellite–ground transmission links will cause spatial and temporal variations,respectively,resulting in the breakdown of the time-of-flight reciprocity on which optical two-way time-frequency transfer is based.Here,we experimentally simulate the atmospheric effects by two-way spatio-temporally separated links between two stationary terminals located 113 km apart and measure the effects for optical two-way time-frequency transfer.Our experiment shows that the effect on the link instability is less than 2.3×10^(−19) at 10,000 s.This indicates that when the link instability of satellite-ground optical time-frequency transfer is on the order of 10^(−19),it is not necessary to consider the atmospheric non-reciprocity effects.

低强度脉冲式超声波在脂多糖诱导的RAW264.7巨噬细胞分化中的抗炎和抗氧化作用

目的研究低强度脉冲式超声波(LIPUS)对RAW264.7巨噬细胞极化的影响及相关分子机制。方法100 ng/mL脂多糖(LPS)和10 ng/mL白细胞介素(IL)-4诱导巨噬细胞RAW264.7分别向M1和M2型极化,45 mW/cm2强度LIPUS对巨噬细胞处理25 min。采用流式细胞术检测巨噬细胞氧化应激活性氧(ROS)水平、M1分化标志物CD80和CD11b,以及M2分化标志物CD163的表达水平。采用反转录聚合酶链反应(RT-PCR)技术检测CD80、CD11b、核转录因子κB(NF-κB)p65、肿瘤坏死因子α(TNF-α)、白细胞介素(IL)-1β和IL-6的mRNA水平。采用Western blot技术检测细胞p65、p-p65、TNF-α、IL-1β和IL-6表达水平。采用流式细胞术检测细胞培养上清TNF和IL-6表达水平。结果LIPUS可明显减少LPS诱导的RAW264.7细胞ROS水平。LPS诱导后,RAW264.7细胞M1分化标志物CD80和CD11b表达和转录水平均上调;LIPUS可抑制LPS对RAW264.7细胞向M1的诱导,差异具有统计学意义。并且,LIPUS可促进IL-4诱导的巨噬细胞M2分化标志物CD163表达。LPS诱导的RAW264.7细胞炎症因子NF-κB p65、TNF-α、IL-1β和IL-6 mRNA水平上调,LIPUS可下调这些炎症因子的mRNA水平,差异均具有统计学意义。LIPUS抑制了LPS对RAW264.7细胞因子蛋白p65和p-p65、IL-1β、TNF-α和IL-6蛋白表达上调的作用。胰酶可以通过激活ROS-NF-κB通路,回复LIPUS促进巨噬细胞M1分化的作用。结论LIPUS可通过ROS-NF-κB抑制RAW264.7向巨噬细胞M1型分化,促进RAW264.7向巨噬细胞M2型分化。氧化应激和炎症因子表达水平被抑制。LIPUS可能在牙周疾病中起到抑制氧化和炎症的作用,从而发挥对牙周疾病的治疗功能。

中国乳腺癌自然史参数选择的优化方法

乳腺癌是女性最常见的恶性肿瘤之一。为了提出有效的筛查策略并评估其效果,一个基本且重要的步骤是在中国乳腺癌自然史模型中选择合适的参数,即转移概率.选择合理的转移概率有两个挑战.首先,由于乳腺癌的流行病学特性,其他国家使用的转移概率不一定适用于中国.其次,可用的筛查样本数据很少,这使得传统的基于统计的方法(如极大似然估计法)失效.本文从优化角度提出一种乳腺癌自然史参数选择的方法,基于公布的统计数据建立数学优化模型.该模型的挑战在于目标函数高度非线性且无显式表达式,本文提出一种坐标下降算法来处理这个挑战.最后,本文提出一种最佳匹配方法来估计每个转移概率的分布.本文所提出的方法为进一步提出合理的中国乳腺癌筛查策略和分析乳腺癌的经济负担提供了坚实的基础.

Numerical and Experimental Investigation on the Performance of Lean Burn Catalytic Combustion for Gas Turbine Application

This manuscript presents our numerical and experimental results regarding the performance characteristics of lean burn catalytic combustion for gas turbine application. The reactant transport was assumed to be controlled by both bulk diffusion as well as surface kinetics, implemented by means of an approximate reaction rate equation and empirical coefficients to incorporate reaction mechanism. Experimental and numerical results were compared to examine the effects of methane mole fraction, inlet temperature, operating pressure, velocity and hydrogen species on combustion intensity. The results indicate that inlet temperature is the most significant parameter that impacts operation of the catalytic combustor and the most effective methods for improving the methane conversion are increasing the inlet temperature and increasing the methane mole fraction. Simulations from 1D heterogeneous plug flow model can capture the trend of catalytic combustion and describe the behavior of the catalytic monolith in detail. The addition of hydrogen will provide heat release by the exothermic combustion reaction so that the reactants reach a temperature at which methane oxidation can light-off.

Quantum interference with independent single-photon sources over 300 km fiber

In the quest to realize a scalable quantum network,semiconductor quantum dots(QDs)offer distinct advantages,including high single-photon efficiency and indistinguishability,high repetition rate(tens of gigahertz with Purcell enhancement),interconnectivity with spin qubits,and a scalable on-chip platform.However,in the past two decades,the visibility of quantum interference between independent QDs rarely went beyond the classical limit of 50%,and the distances were limited from a few meters to kilometers.Here,we report quantum interference between two single photons from independent QDs separated by a 302 km optical fiber.The single photons are generated from resonantly driven single QDs deterministically coupled to microcavities.Quantum frequency conversions are used to eliminate the QD inhomogeneity and shift the emission wavelength to the telecommunication band.The observed interference visibility is 0.670.02(0.930.04)without(with)temporal filtering.Feasible improvements can further extend the distance to∼600 km.Our work represents a key step to long-distance solid-state quantum networks.

Chaetocin reactivates the lytic replication of Epstein-Barr virus from latency via reactive oxygen species

Oxidative stress,regarded as a negative effect of free radicals in vivo,takes place when organisms suffer from harmful stimuli.Some viruses can induce the release of reactive oxygen species(ROS) in infected cells,which may be closely related with their pathogenicity.In this report,chaetocin,a fungal metabolite reported to have antimicrobial and cytostatic activity,was studied for its effect on the activation of latent Epstein-Barr virus(EBV) in B95-8 cells.We found that chaetocin remarkably up-regulated EB V lytic transcription and DNA replication at a low concentration(50 nmol L^(-1).The activation of latent EBV was accompanied by an increased cellular ROS level.N-acetyl-L-cy steine(NAC),an ROS inhibitor,suppressed chaetocin-induced EBV activation.Chaetocin had little effect on histone H3K9 methylation,while NAC also significantly reduced H3K9 methylation.These results suggested that chaetocin reactivates latent EBV primarily via ROS pathways.

Part-load Performance Characteristics of a Lean Burn Catalytic Combustion Gas Turbine System

The purpose of this study is to compare the part-load performance of a lean burn catalytic combustion gas turbine (LBCCGT) system in three different control modes: varying fuel, bleeding off the fuel mixture flow after the compressor and varying rotational speed. The conversions of methane species for chemical process are considered. A 1D heterogeneous plug flow model was utilized to analyze the system performance. The actual turbomachinery components were designed and predicted performance maps were applied to system performance research. The part-load characteristics under three control strategies were numerically investigated. The main results show that: the combustor inlet temperature is a significant factor that can significantly affect the part-load characteristics of the LBCCGT system; the rotational speed control mode can provide the best performance characteristics for part-load operations; the operation range of the bleed off mode is narrower than that of the speed control mode and wider than that of the fuel only mode; with reduced power, methane does not achieve full conversion over the reactor at the fuel only control mode, which will not warrant stable operation of the turbine system; the thermal efficiency of the LBCCGT system at fuel only control strategy is higher than that at bleed off control strategy within the operation range.