Growth differentiation factor 11 promotes macrophage polarization towards M2 to attenuate myocardial infarction via inhibiting Notch1 signaling pathway

Background:Myocardial infarctions(MI)is a major threat to human health especially in people exposed to cold environment.The polarization of macrophages towards different functional phenotypes(M1 macrophages and M2 macrophages)is closely related to MI repairment.The growth differentiation factor 11(GDF11)has been reported to play a momentous role in inflammatory associated diseases.In this study,we examined the regulatory role of GDF11 in macrophage polarization and elucidated the underlying mechanisms in MI.Methods:In vivo,the mice model of MI was induced by permanent ligation of the left anterior descending coronary artery(LAD),and mice were randomly divided into the sham group,MI group,and MI+GDF11 group.The protective effect of GDF11 on myocardial infarction and its effect on macrophage polarization were verified by echocardiography,triphenyl tetrazolium chloride staining and immunofluorescence staining of heart tissue.In vitro,based on the RAW264.7 cell line,the effect of GDF11 in promoting macrophage polarization toward the M2 type by inhibiting the Notch1 Signaling pathway was validated by qRT-PCR,Western blot,and flow cytometry.Results:We found that GDF11 was significantly downregulated in the cardiac tissue of MI mice.And GDF11 supplementation can improve the cardiac function.Moreover,GDF11 could reduce the proportion of M1 macrophages and increase the accumulation of M2 macrophages in the heart tissue of MI mice.Furthermore,the cardioprotective effect of GDF11 on MI mice was weakened after macrophage clearance.At the cellular level,application of GDF11 could inhibit the expression of M1 macrophage(classically activated macrophage)markers iNOS,interleukin(IL)-1β,and IL-6 in a dose-dependent manner.In contrast,GDF11 significantly increased the level of M2 macrophage markers including IL-10,CD206,arginase 1(Arg1),and vascular endothelial growth factor(VEGF).Interestingly,GDF11 could promote M1 macrophages polarizing to M2 macrophages.At the molecular level,GDF11 significantly down-regulated the Notch1 signaling pathway,the activation of which has been demonstrated to promote M1 polarization in macrophages.Conclusions:GDF11 promoted macrophage polarization towards M2 to attenuate myocardial infarction via inhibiting Notch1 signaling pathway.

Propagation of Gaussian Schell-Model Array Beams through a Jet Engine Exhaust

Here a Gaussian Shell Model Array (GSMA) beam is used to investigate the propagation characteristics in the jet engine exhaust region. It has great significance to improve various optical systems for wide application in trapping cold atoms, creating gratings, and atmospheric optical communication. We calculate analytical formulas for the spectral density (SD) and the propagation factors Mx2 and My2 of a GSMA beam. The influence of inner scale of turbulence in the jet engine exhaust region on its power spectrum has been also analyzed. According to these results, the influence of turbulence in a jet engine exhaust on a GSMA beam has been reduced by changing the parameters of light source and turbulence. For example, it is an excellent tool for mitigation of the jet engine exhaust-induced anisotropy of turbulence to increase the source coherence length, the root-mean-squared (rms) beam width, the wavelength or reduce the outer scale of turbulence.

M2-factor of high-power laser beams through a multi-apertured ABCD optical system

Based on the generalized truncated second-order moments,an approximate analytical formula of the beam propagation factor M^2 of high-power laser beams passing through the optical system with multiple hard-edged apertures is deduced.Numerical examples of the beams passing through an aperture-spatial filter are enclosed,and the influences of amplitude modulations(AMs)and phase fluctuations(PFs)on the beam propagation quality of high-power laser beams passing through the multi-apertured ABCD optical system are considered and discussed.It is shown that PFs are able to degrade the beam propagation quality of laser beams more than AMs when the high-power laser beams passing through the aperture-spatial filter,furthermore,one or two aperture-lens optical systems configured appropriate aperture parameters are both able to upgrade the beam propagation quality of high-power laser beams.The M2 factor of Gaussian beam passing through the multi-aperture optical system is a special case in this paper.

Insulin-like growth factor 2 mRNA-binding protein 1 promotes cell proliferation via activation of AKT and is directly targeted by microRNA-494 in pancreatic cancer

BACKGROUND Studies have shown that insulin-like growth factor 2 mRNA-binding protein 1(IGF2BP1)plays critical roles in the genesis and development of human cancers.AIM To investigate the clinical significance and role of IGF2BP1 in pancreatic cancer.METHODS Expression levels of IGF2BP1 and microRNA-494(miR-494)were mined based on Gene Expression Omnibus datasets and validated in both clinical samples and cell lines by quantitative real-time polymerase chain reaction and Western blot.The relationship between IGF2BP1 expression and clinicopathological factors of pancreatic cancer patients was analyzed.The effect and mechanism of IGF2BP1 on pancreatic cancer cell proliferation were investigated in vitro and in vivo.Analyses were performed to explore underlying mechanisms of IGF2BP1 upregulation in pancreatic cancer and assays were carried out to verify the posttranscriptional regulation of IGF2BP1 by miR-494.RESULTS We found that IGF2BP1 was upregulated and associated with a poor prognosis in pancreatic cancer patients.We showed that downregulation of IGF2BP1 inhibited pancreatic cancer cell growth in vitro and in vivo via the AKT signaling pathway.Mechanistically,we showed that the frequent upregulation of IGF2BP1 was attributed to the downregulation of miR-494 expression in pancreatic cancer.Furthermore,we discovered that reexpression of miR-494 could partially abrogate the oncogenic role of IGF2BP1.CONCLUSION Our results revealed that upregulated IGF2BP1 promotes the proliferation of pancreatic cancer cells via the AKT signaling pathway and confirmed that the activation of IGF2BP1 is partly due to the silencing of miR-494.

Interaction of Mechanical and Electrochemical Factors duringCorrosion Fatigue of Fe-26Cr-1Mo Stainless Steel in 1M H_2SO_4 Solution

The cyclic plastic straining electrode technique has been used to investigate the transient electrochemical behaviour of Fe-26Cr1Mo stainless steel in 1M H2SO4 solution at a passive potential.The influence of plastic strain amplitude and plastic strain rate on the dissolution current response was analysed. The experimental results showed that the transient current was dependent on the competitive process of the surface film rupture and repassivation of the new surface. The high plastic strain amplitude and the high plastic strain rate caused a change of electrochemical activity of specimen surface. In the condition of low strain amplitude and strain rate, the characteristics of current response was mainly relative tp the process of new surface repassivation.The competition kinetics has been analysed through the comparison of plastic strain rate and repassivating rate

血清PCSK9、vWF和apoM水平在2型糖尿病并发大血管病变中的诊断价值

目的观察血清转化酶枯草溶菌素9(PCSK9)、血管性假血友病因子(vWF)和载脂蛋白M(apoM)水平在2型糖尿病并发大血管病变中的诊断价值。方法选择2018年1月至2021年6月在该院就诊的210例2型糖尿病患者纳入2型糖尿病组。选择同期在该院行健康体检的75例健康者纳入健康对照组。根据大血管病变的诊断标准将2型糖尿病患者分为单纯糖尿病组(118例)和大血管病变组(92例)。观察各组血清PCSK9、vWF和apoM水平变化,对2型糖尿病并发大血管病变进行单因素和多因素分析,比较2型糖尿病患者治疗前后血清PCSK9、vWF和apoM水平变化,并分析3项指标在2型糖尿病并发大血管病变中的诊断效能。结果2型糖尿病组血清PCSK9和vWF水平明显高于健康对照组,而血清apoM水平明显低于健康对照组,差异有统计学意义(P<0.05)。治疗前大血管病变组血清PCSK9和vWF水平明显高于单纯糖尿病组,差异有统计学意义(P<0.05);治疗后两组血清PCSK9和vWF水平均较治疗前明显降低,但大血管病变组仍高于单纯糖尿病组,差异有统计学意义(P<0.05)。治疗前大血管病变组血清apoM水平明显低于单纯糖尿病组,差异有统计学意义(P<0.05);治疗后两组血清apoM水平均较治疗前明显升高,但大血管病变组仍低于单纯糖尿病组,差异有统计学意义(P<0.05)。单因素分析显示,大血管病变组年龄≥60岁及糖尿病病程≥10年比例、甘油三酯和低密度脂蛋白胆固醇水平明显高于单纯糖尿病组,差异有统计学意义(P<0.05)。多因素分析显示PCSK9、vWF水平升高是2型糖尿病并发大血管病变的独立危险因素(P<0.05),血清apoM水平升高是2型糖尿病并发大血管病变的保护因素(P<0.05)。血清PCSK9、vWF和apoM联合检测诊断2型糖尿病并发大血管病变的灵敏度为89.1%,特异度为90.7%,曲线下面积(AUC)为0.956,AUC明显高于PCSK9(Z=4.167,P<0.01)、vWF(Z=4.056,P<0.01)和apoM(Z=5.183,P<0.01)单项指标检测,而3项指标之间的AUC差异无统计学意义(P>0.05)。结论PCSK9、vWF和apoM参与了2型糖尿病并发大血管病变的过程,3项指标联合检测对诊断2型糖尿病并发大血管病变具有较高的效能。

Macrophage colony-stimulating factor expressed in non-cancer tissues provides predictive powers for recurrence in hepatocellular carcinoma

AIM To investigate the role of macrophage colony-stimulating factor(M-CSF) in patients with hepatocellular carcinoma(HCC) after surgery. METHODS Expression of M-CSF, distribution of M2 macrophages(Mφs), and angiogenesis were assessed in the liver, including tumors and peritumoral liver tissues. The prognostic power of these factors was assessed. Mouse isolated hepatic Mφs or monocytes were cultured with media containing M-CSF. The concentration of vascular endothelial growth factor(VEGF) in media was assessed. Furthermore, the role of the M-CSF-matured hepatic Mφs on proliferation of the vascular endothelial cell(VEC) was investigated. RESULTS A strong correlation between the expressions of M-CSF and CD163 was observed in the peritumoral area. Also, groups with high density of M-CSF, CD163 or CD31 showed a significantly shorter time to recurrence(TTR) than low density groups. Multivariate analysis revealedthe expression of M-CSF or hepatic M2Mφs in the peritumoral area as the most crucial factor responsible for shorter TTR. Moreover, the expression of M-CSF and hepatic M2Mφs in the peritumoral area had better predictable power of overall survival. Values of VEGF in culture media were significantly greater in the hepatic Mφs compared with the monocytes. Proliferation of the VEC was greatest in the cells co-cultured with hepatic Mφs when M-CSF was present in media.CONCLUSION M-CSF increases hepatocarcinogenesis, most likely by enhancing an angiogenic factor derived from hepatic Mφ and could be a useful target for therapy against HCC.

Th17/Treg balance and macrophage polarization ratio in lower extremity arteriosclerosis obliterans

Objective:To explore the balance of peripheral blood T helper 17 cells/regulatory T cell(Th17/Treg)ratio and the polarization ratio of M1 and M2 macrophages in lower extremity arteriosclerosis obliterans(ASO).Methods:A rat model of lower extremity ASO was established,and blood samples from patients with lower extremity ASO before and after surgery were obtained.ELISA was used to detect interleukin 6(IL-6),IL-10,and IL-17.Real-time RCR and Western blot analyses were used to detect Foxp3,IL-6,IL-10,and IL-17 expression.Moreover,flow cytometry was applied to detect the Th17/Treg ratio and M1/M2 ratio.Results:Compared with the control group,the iliac artery wall of ASO rats showed significant hyperplasia,and the concentrations of cholesterol and triglyceride were significantly increased(P<0.01),indicating the successful establishment of ASO.Moreover,the levels of IL-6 and IL-17 in ASO rats were pronouncedly increased(P<0.05),while the IL-10 level was significantly decreased(P<0.05).In addition to increased IL-6 and IL-17 levels,the mRNA and protein levels of Foxp3 and IL-10 in ASO rats were significantly decreased compared with the control group.The Th17/Treg and M1/M2 ratios in the ASO group were markedly increased(P<0.05).These alternations were also observed in ASO patients.After endovascular surgery(such as percutaneous transluminal angioplasty and arterial stenting),all these changes were significantly improved(P<0.05).Conclusions:The Th17/Treg and M1/M2 ratios were significantly increased in ASO,and surgery can effectively improve the balance of Th17/Treg,and reduce the ratio of M1/M2,and the expression of inflammatory factors.

Techniques trend analysis of propagating laser beam quality measurement

Different methods of measuring a propagating laser beam quality are summarized.The disadvantages in traditional way in measuring a laser beam quality is analyzed and the insufficiencies of the Shack-Hartmannin method which is commonly using wave front technique at present is pointed out.Finally,the transmission intensity equation based(TIE-based)measuring way in a laser beam quality evaluation and the corresponding advantages are discussed,which is believed to be a deve-l oping trend in laser beam evaluation.

Potential Benefits and Obstacles of the Use of Internet of Things in Saudi Universities: Empirical Study

Internet of Things (IoT) among of all the technology revolutions has been considered the next evolution of the internet. IoT has become a far more popular area in the computing world. IoT combined a huge number of things (devices) that can be connected through the internet. The purpose: this paper aims to explore the concept of the Internet of Things (IoT) generally and outline the main definitions of IoT. The paper also aims to examine and discuss the obstacles and potential benefits of IoT in Saudi universities. Methodology: the researchers reviewed the previous literature and focused on several databases to use the recent studies and research related to the IoT. Then, the researchers also used quantitative methodology to examine the factors affecting the obstacles and potential benefits of IoT. The data were collected by using a questionnaire distributed online among academic staff and a total of 150 participants completed the survey. Finding: the result of this study reveals there are twelve factors that affect the potential benefits of using IoT such as reducing human errors, increasing business income and worker’s productivity. It also shows the eighteen factors which affect obstacles the IoT use, for example sensors’ cost, data privacy, and data security. These factors have the most influence on using IoT in Saudi universities.

IGF_(2)BP_(1)调控lncRNA NEAT1在类风湿关节炎中的作用

目的:类风湿关节炎(rheumatoid arthritis,RA)是一种常见的全身性自身免疫疾病,可能导致关节变形和功能障碍。本研究旨在探索胰岛素样生长因子-2 mRNA结合蛋白1(insulin like growth factor 2 mRNA binding protein 1,IGF_(2)BP_(1))在RA中的表达水平,以及其对长链非编码RNA(long non-coding RNA,lncRNA)核丰富转录本1(nuclear paraspeckle assembly transcript 1,NEAT1)稳定性的影响和在RA发病机制中的作用。方法:通过GEO(Gene Expression Omnibus)数据库获取RA数据集,并将其分为正常对照组和RA组,使用R软件分析获取N^(6)-甲基腺苷(N^(6)-methyladenosine,m^(6)A)相关的甲基化酶的表达量并进行差异分析。分析差异表达的m^(6)A甲基化酶与lncRNA NEAT1的相关性。通过在线网站ENCORI预测与lncRNA NEAT1结合的蛋白质,并与lncRNA NEAT1表达相关的m^(6)A甲基化酶取交集,从而获取关键基因。通过RNA蛋白质相互作用分析实验(RNA pull-down)验证在RA滑膜细胞中NEAT1与关键基因结合的情况。通过蛋白质印迹法验证关键基因在正常滑膜细胞和RA滑膜细胞中的表达水平。在RA滑膜细胞中转染关键基因的小干扰RNA,通过real-time RT-PCR检测NEAT1在滑膜细胞中的表达水平。结果:差异分析结果显示:与正常对照组相比,共有8个m^(6)A甲基化基因在RA组中存在差异表达,其中IGF_(2)BP_(1)、甲基转移酶样蛋白14(methyltransferase 14,N^(6)-adenosine-methyltransferase subunit,MEEEL14)与lncRNA NEAT1存在相关性;ENCORI预测结果显示:共有23个蛋白质能够与lncRNA NEAT1结合,与NEAT1共表达m^(6)A甲基化酶取交集,获得NEAT1相关m^(6)A甲基化蛋白IGF_(2)BP_(1)。蛋白质印迹法显示:与正常对照组相比,RA组中IGF_(2)BP_(1)蛋白在RA滑膜细胞中表达升高(P<0.05);RNA pull-down结果显示IGF_(2)BP_(1)蛋白与NEAT1结合;real-time RT-PCR的结果表明:敲减IGF_(2)BP_(1)可显著降低NEAT1 mRNA表达水平(P<0.01)。结论:IGF_(2)BP_(1)可能通过稳定lncRNA NEAT1表达参与RA发病,调控IGF_(2)BP_(1)水平可能是一种新的治疗RA的方法。

^(60)Coγ射线处理花卉后M_2代生理特性变化对小气候要素的响应

大丽菊和球根海棠花卉的根茎经 1 0Gy60 Coγ射线处理后 ,在M2 代生长盛期分别测定两类处理花卉叶片的生理特性和小气候要素。经岑回归分析 ,结果显示 ,M2 代大丽菊的蒸腾速率、气孔导度、细胞间隙CO2 浓度对小气候要素反应敏感 ,而光合速率反应不敏感 ,球根海棠则反应迟钝。

检测恶性腹水中VEGF、CD44v6和MMP-2、MMP-9的临床意义

背景及目的:恶性腹水中找到癌细胞有确诊意义,但阳性率很低。因此从腹水中寻找理想的癌性标记物已成为当前研究的主要课题。本课题拟通过检测腹水中血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)、细胞粘附分子CD44v6、基质金属蛋白酶-2,-9(matrixmetalloproteinase-2,-9,MMP-2,-9)的水平并进行分析,以期为临床腹水诊治提供科学依据。方法:收集肝硬化腹水36例、结核性腹水8例、恶性腹水23例。采用ELISA法检测VEGF、CD44v6含量,用明胶酶谱法检测MMP-2,-9活性。结果:恶性腹水中VEGF、CD44v6含量分别为(640.74±264.81)ng/L、(89.22±38.20)μg/L,明显高于肝硬化腹水犤(67.05±51.91)ng/L,(44.79±18.02)μg/L犦和结核性腹水犤(88.25±24.12)ng/L,(50.25±12.57)μg/L犦(P<0.01)。肝硬化腹水、结核性腹水不能检出MMP-2,-9,而恶性腹水MMP-2检出率为87.0%,MMP-9检出率为78.3%。结论:恶性腹水中VEGF、CD44v6水平显著升高而MMP-2,-9阳性。联合检测腹水中VEGF、CD44v6、MMP-2,-9的水平可作为临床良、恶性腹水的鉴别诊断依据之一。

由M^2参数定义的光束传输变换理论

本文推导了任意光束与Ｍ２参数有关的光腰和发散角经过薄透镜的变换规律，定义了广义的Ｒ（ｚ），导出了广义的ＡＢＣＤ法则。

阶跃光纤低阶线偏振模的M^2因子分析

针对阶跃光纤输出低阶线偏振模(Linear Polarization,LP),利用二阶距定束宽,多点拟合法计算了几个低阶LPmn模相干和非相干叠加时的M2因子.结果表明,对同一LPmn模式,光纤的归一化频率参量V减小到截止频率时,M2因子出现峰值;当V远离截止频率时M2因子趋于一定值.低阶LPmn模非相干叠加时,叠加后的较高阶模成分越大,合成光束的光束质量越差,光束在一定的条件下可能比基模更接近于理想高斯光束;而相干叠加时,合成后的M2因子可以大于参与叠加的较高阶模的光束质量因子.

正规方程组求解激光束质量M^2因子方法的研究

为提高双曲线拟合精度和速度,克服M2因子测量过程中受到随机误差的影响,采用正规方程组拟合双曲线的方法,给出了三角分解法求解正规方程组的快速数值算法。实验结果表明,采用正规方程组求解光束质量M2因子与奇异值分解法所得结果是一致的,且该方法速度快、精度高,运算速度可提高一个数量级。

截断平顶高斯光束M^2因子的比较研究

使用熵束宽、渐近分析和环围功率法对截断平顶高斯光束的束腰宽度w、远场发散角θ0和M2因子作了比较研究.结果表明:按不同束宽定义得到的截断平顶高斯光束的w、θ0和M2因子不同,且与截断参量a/ w0(a为光阑半宽度,w0为平顶高斯光束初始束腰宽度)有关.随a/ w0的增加,三种方法计算得到的w、θ0和M2都分别趋于某常量.

非傍轴平顶高斯光束M^2因子两种定义的比较研究

基于功率密度的二阶矩方法,推导出了非傍轴平顶高斯(FG)光束束宽和远场发散角的解析表达式·研究表明,当w0/λ→0时,远场发散角趋于渐近值θmax=63.435°,与阶数无关·使用非傍轴高斯光束代替傍轴高斯光束作为理想光束,研究了非傍轴FG光束的M2因子,并与传统定义的M2因子作了比较·在非傍轴范畴,非傍轴FG光束的M2因子不仅与阶数N有关,而且与w0/λ有关·按照定义,当w0/λ→0时,非傍轴FG光束的M2因子不等于0,对阶数N=1,2,3时,M2因子分别趋于0.913,0.882和0.886·当N→∞时,M2因子取最小值M2min=0.816·

圆形平顶高斯光束阵列在湍流大气传输中的M^2因子

应用Wigner分布函数的二阶矩定义和拓展Huygens-Fresnel原理研究了圆形平顶高斯光束阵列在湍流大气传输中的光束性质,得到其传输质量因子(M^2因子)的解析表达式,进行了相应的数值计算和模拟。结果表明:在湍流大气中传输时,圆形平顶高斯光束阵列的传输质量因子随传播距离、湍流大气结构常数的增大和束腰宽度的减小而增大;当光束阵列阶数一定,阵列个数不断增加时,其传输质量因子先保持不变,然后开始减小,最后不再减小而保持这个定值不变;当光束阵列的个数一定,阶数不断增加时,其传输质量因子减小,最后不再减小而保持不变。在自由空间中传输时,圆形平顶高斯光束阵列的传输质量因子保持不变。

非傍轴截断双曲余弦高斯光束的M^2因子

基于功率密度的二阶矩方法,对非傍轴截断双曲余弦高斯(ChG)光束的束宽、远场发散角和M2 因子进行了研究。数值计算结果表明,非傍轴截断ChG光束的M2因子不仅与截断参数δ、偏心参数α有 关,而且与初始束腰宽度和波长之比ω0／λ有关。在δ足够小时,M2因子可小于1。当δ→0时,远场发 散角趋于渐近值63．435°。对于α=0(Ω0=0)和δ→∞的特例,我们的结果分别退化为非傍轴截断高斯 光束和非傍轴无截断ChG光束的M2因子。