Lysine-specific demethylase 1 inhibitor rescues the osteogenic ability of mesenchymal stem cells under osteoporotic conditions by modulating H3K4 methylation

Bone tissue engineering may be hindered by underlying osteoporosis because of a decreased osteogenic ability of autologous seed cells and an unfavorably changed microenvironment in these patients. Epigenetic regulation plays an important role in the developmental origins of osteoporosis; however, few studies have investigated the potential of epigenetic therapy to improve or rescue the osteogenic ability of bone marrow mesenchymal stem cells(BMMSCs) under osteoporotic conditions. Here, we investigated pargyline, an inhibitor of lysine-specific demethylase 1(LSD1), which mainly catalyzes the demethylation of the di- and mono-methylation of H3K4. We demonstrated that 1.5 mmol·Lpargyline was the optimal concentration for the osteogenic differentiation of human BMMSCs. Pargyline rescued the osteogenic differentiation ability of mouse BMMSCs under osteoporotic conditions by enhancing the dimethylation level of H3K4 at the promoter regions of osteogenesis-related genes. Moreover, pargyline partially rescued or prevented the osteoporotic conditions in aged or ovariectomized mouse models, respectively. By introducing the concept of epigenetic therapy into the field of osteoporosis, this study demonstrated that LSD1 inhibitors could improve the clinical practice of MSC-based bone tissue engineering and proposes their novel use to treat osteoporosis.

Truss-type maintenance devices and corresponding pipeline lifting control strategies

For new submarine pipeline maintenance lifting equipment,a specialized analysis model is constructed in this study.A pipeline can be divided into the lifted portion and the touch-down portion that lies on the seabed,and each of these portions can be analyzed separately by converting the continuity conditions at the touch-down points to boundary conditions.The typical two-point sequence secant iterative technique is used to obtain the unknown lifted length and determine pipeline lifting confgurations.The BVP4C module in MATLAB software is used to solve this multiple-point boundary value problem issued from frst-order diferential equations.Also,the triple-point lifting mode of truncated maintenance and the two-point lifting mode of online maintenance are discussed.When the lifted heights at truss positions are shown,the lifting deformation,lifting forces,bending moment distribution,and axial force distribution can be analyzed using a dedicated analysis program.Numerical results can then be used to design a lifting strategy to protect the pipeline.

Hybrid Simulation of Duty Cycle Influences on Pulse Modulated RF SiH_4/Ar Discharge

A one-dimensional fluid/Monte-Carlo（MC）hybrid model is developed to describe capacitively coupled SiH_4/Ar discharge,in which the lower electrode is applied by a RF source and pulse modulated by a square-wave,to investigate the modulation effects of the pulse duty cycle on the discharge mechanism.An electron Monte Carlo simulation is used to calculate the electron energy distribution as a function of position and time phase.Rate coefficients in chemical reactions can then be obtained and transferred to the fluid model for the calculation of electron temperature and densities of different species,such as electrons,ions,and radicals.The simulation results show that,the electron energy distribution f（ε）is modulated evidently within a pulse cycle,with its tail extending to higher energies during the power-on period,while shrinking back promptly in the afterglow period.Thus,the rate coefficients could be controlled during the discharge,resulting in modulation of the species composition on the substrate compared with continuous excitation.Meanwhile,more negative ions,like Si H_3^-and Si H_2^-,may escape to the electrodes owing to the collapse of ambipolar electric fields,which is beneficial to films deposition.Pulse modulation is thus expected to provide additional methods to customize the plasma densities and components.

Pharmacological kinetics of BmK AS, a sodium channel site 4-specific modulator on Na_v1.3

Objective In this study, the pharmacological kinetics of Buthus martensi Karsch （BmK） AS, a specific modulator of voltage-gated sodium channel site 4, was investigated on Nav1.3 expressed in Xenopus oocytes. Methods Two-electrode voltage clamp was used to record the whole-cell sodium current. Results The peak currents of Nav1.3 were depressed by BmK AS over a wide range of concentrations （10, 100, and 500 nmol/L）. Most remarkably, BmK AS at 100 nmol/L hyperpolarized the voltage-dependence and increased the voltage-sensitivity of steady-state activation/inactivation. In addition, BmK AS was capable of hyperpolarizing not only the fast inactivation but also the slow inactivation, with a greater preference for the latter. Moreover, BmK AS accelerated the time constant and increased the ratio of recovery in Nav1.3 at all concentrations. Conclusion This study provides direct evidence that BmK AS facilitates steady-state activation and inhibits slow inactivation by stabilizing both the closed and open states of the Nav1.3 channel, which might result from an integrative binding to two receptor sites on the voltage-gated sodium channels. These results may shed light on therapeutics against Nav1.3-targeted pathology.

《快乐阅读》七年级2012年上半年第2期 总第1456期 Module 4 Passage one My vacation教学案例

教学目标知识目标:(1)通过对本文的阅读,了解文中的假期活动,从而学习英语阅读中的概要策略。(2)通过对本文的阅读,获取本课文章的主旨大意和找出相应的细节信息。能力目标:(1)能初步掌握将阅读材料浓缩,进行概要的阅读方法。(2)通过对课文的信息检索,使学生能够用过去式来表达课文中自己的假期旅行经历。情感目标:(1)培养学生自主学习发现探究、积极与他人合作。