ACVR1, a Therapeutic Target of Fibrodysplasia Ossificans Progressiva, Is Negatively Regulated by miR-148a

Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disorder of skeletal malformations and progressive extraskeletal ossification. There is still no effective treatment for FOP. All FOP individuals harbor conserved point mutations in ACVR1 gene that are thought to cause ACVR1 constitutive activation and activate BMP signal pathway. The constitutively active ACVR1 is also found to be able to cause endothelial-to-mesenchymal transition (EndMT) in endothelial cells, which may cause the formation of FOP lesions. MicroRNAs (miRNAs) play an essential role in regulating cell differentiation. Here, we verified that miR-148a directly targeted the 3' UTR of ACVR1 mRNA by reporter gene assays and mutational analysis at the miRNA binding sites, and inhibited ACVR1 both at the protein level and mRNA level. Further, we verified that miR-148a could inhibit the mRNA expression of the Inhibitor of DNA binding (Id) gene family thereby suppressing the BMP signaling pathway. This study suggests miR-148a is an important mediator of ACVR1, thus offering a new potential target for the development of therapeutic agents against FOP.     

Efficient production of L-(+)-lactic acid from raw starch by Streptococcus bovis 148

Streptococcus bovis 148 was found to produce L-(+)-lactic acid directly from soluble and raw starch substrates at pH 6.0. Productivity was highest at 37 degrees C, with 14.7 g/l lactic acid produced from 20 g/l raw starch. The yield and optical purity of L-lactic acid were 0.88 and 95.6%, respectively.     

液动冲击器功率传递理论分析及应用研究

运用波动理论分析了液动冲击器结构对能量传递的影响，室内模拟试验结果与波动理论分析计算结果有很高的吻合度。推导出了功率传递效率模型。以花岗岩和大理石为对象，分别求出了不同钻头的钻入系数和回弹系数。分析认为原设计液动冲击器功率传递机构不够合理，指导改进后的液动冲击器简化了结构、提高了强度，能量传递效率提高近30％，现场应用表明，改进后的液动冲击器在硬地层中可提高机械钻速30％以上。     

80C51单片机扩展外部中断源的几种方法

80C51单片机只有2个外部中断源:和,而在实际应用系统中可能有两个以上的外部中断源.这时必须对外部中断源进行扩展.扩展外部中断源的常用方法有:定时/计数器扩展法,中断、查询相结合扩展法和74LS148硬件电路扩展法,本文分别介绍了这三种方法的软、硬件设计,并作出了比较.     

基于MSP430F148单片机的正弦脉宽调制波的产生

介绍了一种基于面积等效原理,采用查表法产生正弦脉宽调制（SPWM）波的方法。分析了查表法的原理,并结合1Hz的SPWM波产生实例,给出了部分程序清单和相关硬件电路图。该实现方法具有电路简单、成本较低、抗干扰性好、误差较小、实现较容易的优点。     

一种基于优先级控制的多路办公电话防盗计费系统

针对在PC机和单片机频繁通信的情况下,传统的主机轮询从机的方式占用大量的CPU时间,效率低,实时性和可靠性很差的缺陷,介绍一种串行通信的新方法——基于编码器74LS148的优先级判定法,实现了PC与单片机一对多通信,有效的解决了办公电话多路控制的问题。实际应用证明,该设计可靠,稳定性好。     

制动鼓铸造工艺性分析

分析了制动鼓产品的材料成分、性能等技术要求及失效机理,比较分析了顶注式、底注式、中间注入式等铸造工艺方法的优缺点及在实际生产中的应用,同时提出利用球墨铸铁材料取代灰铸铁材料生产制动鼓可提高产品的综合性能并大幅度节约能源。     

一种低温用铸钢材料的化学成分与热处理工艺设计

为满足海工装备用铸钢件材料的高强度和低温冲击性能要求,对ASTM A148 105-85铸钢材料的化学成分和热处理工艺进行调整、优化.最终确定该材质的化学成分为:0.25％C、0.5％Si、0.9％Mn、P≤0.02％、S≤0.01％、0.7％Cr、0.50％Mo、0.70％Ni.热处理工艺采用淬火+亚温淬火+高温回火.经过调整和优化,铸钢材料的抗拉强度达到810 MPa、屈服强度达到621MPa、伸长率达到20％、断面收缩率达到47％,-20℃冲击功达到73 J,-40℃冲击功达到42J.     

miR-148a / b 真核表达质粒的构建及其在胰腺癌细胞系中的表达简

目的构建miR-148a／b真核表达质粒,转染胰腺癌AsPC-1细胞,并观察其miR-148a／b的表达水平。方法根据miRBase提供的序列合成miR-148a／b前体,PCR扩增后形成双链,插入线性化真核表达质粒pcDNA3．1,构建pcDNA3．1／miR-148a／b,进行酶切和测序鉴定。将胰腺癌AsPC-1细胞分4组进行质粒转染：转染pcDNA3．1／miR-148a（miR-148a组）、转染pcDNA3．1／miR-148b（miR-148b组）、转染pcDNA3．1（空质粒对照组）和仅加脂质体（空白对照组）。转染48h后,采用定量PCR法检测各组细胞中miR-148a／b的表达量。结果pcDNA3．1／miR-148a／b的酶切和测序与miRBase提供的序列完全一致。转染48h后,miR-148a组AsPC-1细胞中的miR-148a表达量明显高于空质粒对照组和空白对照组（6．76±0．35比1．00±0．54、1．02±0．40,均P〈0．05）,miR-148b组AsPCq细胞中的miR-148b表达量明显高于空质粒对照组和空白对照组（3．28±0．08比1．02±0．35、1．01±0．28,均P〈0．05）。结论成功构建了miR-148a／b真核表达质粒pcDNA3．1／miR-148a／b,该质粒能显著上调胰腺癌AsPC-1细胞的miR-148a／b表达水平。     

miRNA-148b-3p targeting SOCS3 inhibits macrophage M2 polarization by JAK2/STAT3 pathway in immune thrombocytopenia

Aberrant expression of miRNAs is significantly correlated with the occurrence of immune thrombocytopenic purpura (ITP). The immune imbalance of M1/M2 macrophage contributes to the development of ITP. However, the role of miR-148b-3p in macrophage phenotype imbalance remains unknown in ITP. In this study, we aimed to explore whether miR-148b-3p inhibits M2 macrophage polarization in ITP and to investigate the underlying mechanism. Peripheral blood from 22 ITP patients were collected, and real-time PCR confirmed that miR-148b-3p was up-regulated and Western blot analyses detected the expression of SOCS3 was down-regulated. Subsequent dual-luciferase reporter gene assay indicated that miR-148b-3p could bind to SOCS3. Furthermore, we found significant correlation between miR-148b-3p expression and platelet count. Applying gain and lose the function experiments of miR-148b-3p and SOCS3, we demonstrated that suppression of miR-148b-3p or up-regulation of SOCS3 promoted macrophage M2 polarization by inhibiting JAK2/STAT3 pathway. Together, our findings demonstrate that that miR-148b-3p targeting SOCS3 inhibits M2 macrophage polarization via JAK2/STAT3 signaling in ITP.