MiR-1224-5p modulates osteogenesis by coordinating osteoblast/osteoclast differentiation via the Rap1 signaling target ADCY2

MicroRNAs (miRNAs) broadly regulate normal biological functions of bone and the progression of fracture healing and osteoporosis. Recently, it has been reported that miR-1224-5p in fracture plasma is a potential therapy for osteogenesis. To investigate the roles of miR-1224-5p and the Rap1 signaling pathway in fracture healing and osteoporosis development and progression, we used BMMs, BMSCs, and skull osteoblast precursor cells for in vitro osteogenesis and osteoclastogenesis studies. Osteoblastogenesis and osteoclastogenesis were detected by ALP, ARS, and TRAP staining and bone slice resorption pit assays. The miR-1224-5p target gene was assessed by siRNA-mediated target gene knockdown and luciferase reporter assays. To explore the Rap1 pathway, we performed high-throughput sequencing, western blotting, RT-PCR, chromatin immunoprecipitation assays and immunohistochemical staining. In vivo, bone healing was judged by the cortical femoral defect, cranial bone defect and femoral fracture models. Progression of osteoporosis was evaluated by an ovariectomy model and an aged osteoporosis model. We discovered that the expression of miR-1224-5p was positively correlated with fracture healing progression. Moreover, in vitro, overexpression of miR-1224-5p slowed Rankl-induced osteoclast differentiation and promoted osteoblast differentiation via the Rap1-signaling pathway by targeting ADCY2. In addition, in vivo overexpression of miR-1224-5p significantly promoted fracture healing and ameliorated the progression of osteoporosis caused by estrogen deficiency or aging. Furthermore, knockdown of miRNA-1224-5p inhibited bone regeneration in mice and accelerated the progression of osteoporosis in elderly mice. Taken together, these results identify miR-1224-5p as a key bone osteogenic regulator, which may be a potential therapeutic target for osteoporosis and fracture nonunion.Subject terms: Translational research, Cell signalling     

葡聚糖的基体辅助激光解吸/电离飞行时间质谱测定

采用自行设计合成的新基体α-腈基阿魏酸（α-cyano-ferulic acid,简称CFA）并应用激光飞行时间质谱仪的离子偏转功能,对葡聚糖的分子量进行了测定研究。结果表明：与测定糖类物质的常用基体2,5-二羟基苯甲酸（DHB）相比,CFA测定葡聚糖,具有更佳的解吸电离效果,样品易出峰、重现性好、信噪比高;使用仪器的离子偏转器,阻止葡聚糖样品中聚合度较小的离子进入检测器,能显著提高仪器对聚合度较大离子的检测能力,得到质荷比（m/z)更高的质谱峰。     

A Comparative Study of Electron Heat Transport in a Stochastic and a Non‐Stochastic Magnetic Field

We studied the electron heat transport across a non‐local stochastic magnetic field and a non‐local non‐stochastic magnetic field in tokamak plasmas. Analytical results and numerical simulation results were compared with conditions of a stochastic and a non‐stochastic magnetic field respectively in this article. Parameter of stochasticity in perturbed magnetic field was found not tobe a key factor in influencing effective radial heat conductivity in radial direction of tokomak when Chirikov parameter is close to one (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Numerical simulation of transonic limit cycle oscillations using high-order low-diffusion schemes

This paper simulates the NLR7301 airfoil limit cycle oscillation (LCO) caused by fluid–structure interaction (FSI) using Reynolds averaged Navier–Stokes equations (RANS) coupled with Spalart–Allmaras (S–A) one-equation turbulence model. A low diffusion E-CUSP (LDE) scheme with 5th order weighted essentially nonoscillatory scheme (WENO) is employed to calculate the inviscid fluxes. A fully conservative 4th order central differencing is used for the viscous terms. A fully coupled fluid–structural interaction model is employed. For the case computed in this paper, the predicted LCO frequency, amplitudes, averaged lift and moment, all agree excellently with the experiment performed by Schewe et al. The solutions appear to have bifurcation and are dependent on the initial fields or initial perturbation. The developed computational fluid dynamics (CFD)/computational structure dynamics (CSD) simulation is able to capture the LCO with very small amplitudes measured in the experiment. This is attributed to the high order low diffusion schemes, fully coupled FSI model, and the turbulence model used. This research appears to be the first time that a numerical simulation of LCO matches the experiment. The simulation confirms several observations of the experiment.     

三维介观超导环涡旋态的研究

通过数值求解非线性金兹堡-朗道(G-L)方程组,研究了三维介观超导环中的涡旋态。发现了在细环中只能存在巨涡旋态,以及存在顺磁、抗磁迈斯纳效应和间隙性超导现象。在粗环中,发现了多涡旋态和巨涡旋态共存的混合态。相应讨论有助于理解介观超导环中涡旋态相变。     

碳酸盐岩储层流体包裹体差分拉曼光谱的研究

拉曼微探针分析法对单个气液包裹体的化学成分和相态的无破坏性测量来说,目前几乎是唯一最好的方法.但是由于众多因素的影响,特别是主矿物具有较强荧光时,提高信噪比的问题急待解决.本工作对碳酸盐岩储层包裹体样品制成的薄片进行了显微观察、荧光测试及拉曼分析,并进行了空间上横向XY扫描、纵向上深度剖析(Z扫描)和冷热台上变温的流体包裹体筹分拉曼光谱测量方法的研究.结果表明,所得到的差谱揭示了包裹体更真实的光谱曲线,消除了主矿物对包裹体的干扰,以较高的信噪比显现出包裹体中流体(-170℃温度下的冰)位于位移波数3 098 cm-1附近的宽拉曼散射峰,明显的改善了信噪比.     

Isolation of highly pure erlotinib hydrochloride by recrystallization after nucleophilic substitution of an impurity with piperazine

Optimized synthesis and purification of erlotinib hydrochloride (N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazoline-4-amine hydrochloride) were studied. Highly polar piperazine was used in a nucleophilic substitution reaction with the chlorinated intermediate byproduct N-(3-ethynylphenyl)-6(2-chloroethoxy)-7-(2-methoxyethoxy)quinazolin-4-amine hydrochloride. As a result, N-(3-ethynylphenyl)-6(2-chloroethoxy)-7-(2-methoxyethoxy)quinazolin-4-amine hydrochloride was completely transformed to N-(3-ethynylphenyl)-6(2-piperzinoethoxy)-7-(2-methoxyethoxy)quinazolin-4-amine hydrochloride. The polarity of N-(3-ethynylphenyl)-6(2-piperzinoethoxy)-7-(2-methoxyethoxy)quinazolin-4-amine hydrochloride was changed, and its molecule was enlarged. It was easy to remove this larger, more polar, compound by recrystallization. Highly pure erlotinib hydrochloride was obtained with low impurity content (<1 %). The purity of erlotinib hydrochloride was >99.9 %.     

Toxicokinetics and the related metabolites in rainbow trout (Oncorhynchus mykiss) after exposure to decabromodiphenyl ether

Decabromodiphenyl ether (BDE209) is poorly absorbed by mammals, and little information is available on the toxicokinetics of BDE209 and its metabolites in fish. In the present study, rainbow trout (Oncorhynchus mykiss) were administered to 100 ng/g and 500 ng/g body wet weight of BDE209 via a single intraperitoneal injection and parent BDE209 and its metabolites were sequentially monitored for 28 days. The results showed that toxicokinetic profiles of BDE209 could be described by the one-compartment model. In the higher dose group (500 ng/g wet weight), the calculated half-life (t _1/2) and elimination rate (k _e) were 17.7 d and 0.039/d in the liver, and 100.3 d and 0.007/d in the muscle, respectively. Three major methoxylated brominated diphenyl ethers (MeO-BDEs) were detected with 2,2′,4,4′-tetrabromo-5-methoxydiphenyl ether (5-MeO-BDE47) being detected in all tissue samples. There was no significant temporal change of 5-MeO-BDE47 concentration in the muscle, whereas an exponential increase was observed in the liver. Therefore, the metabolism rate of BDE209 depended on the administered dose. BDE209 was hardly accumulated in the muscle of rainbow trout, while the liver was a primary metabolic organ. MeO-BDEs were formed via metabolism of BDE209, which probably played a significant role in fish toxicology as a potential indicator.