Neuronal reprogramming in treating spinal cord injury

Spinal cord injury represents a devastating central nervous system injury that could impair the mobility and sensory function of afflicted patients.The hallmarks of spinal cord injury include neuroinflammation,axonal degeneration,neuronal loss,and reactive gliosis.Furthermore,the formation of a glial scar at the injury site elicits an inhibitory environment for potential neuroregeneration.Besides axonal regeneration,a significant challenge in treating spinal cord injury is to replenish the neurons lost during the pathological process.However,despite decades of research efforts,current strategies including stem cell transplantation have not resulted in a successful clinical therapy.Furthermore,stem cell transplantation faces serious hurdles such as immunorejection of the transplanted cells and ethical issues.In vivo neuronal reprogramming is a recently developed technology and leading a major breakthrough in regenerative medicine.This innovative technology converts endogenous glial cells into functional neurons for injury repair in the central nervous system.The feasibility of in vivo neuronal reprogramming has been demonstrated successfully in models of different neurological disorders including spinal cord injury by numerous laboratories.Several reprogramming factors,mainly the pro-neural transcription factors,have been utilized to reprogram endogenous glial cells into functional neurons with distinct phenotypes.So far,the literature on in vivo neuronal reprogramming in the model of spinal cord injury is still small.In this review,we summarize a limited number of such reports and discuss several questions that we think are important for applying in vivo neuronal reprogramming in the research field of spinal cord injury as well as other central nervous system disorders.

MicroRNAs as potential therapeutics for treating spinal cord injury

MicroRNAs are a class of recently discovered, small non-coding RNAs that have been shown to play essential roles in a vast majority of biological processes. Very little is known about the role of microRNAs during spinal cord injury. This review summarizes the changes in expression levels of microRNAs after spinal cord injury. These aberrant changes suggest that microRNAs play an important role in inflammation, oxidative stress, apoptosis, glial scar formation and axonal regeneration. Given their small size and specificity of action, microRNAs could be potential therapeutics for treating spinal cord injury in the future. There are rapidly developing techniques for manipulating microRNA levels in animals; we review different chemical modification and delivery strategies. These may provide platforms for designing efficient microRNA delivery protocols for use in the clinic.

Corrosion behavior and protection mechanism of carbon steel coated with ethylene chlorotrifluoroethylene(ECTFE)

Ethylene chlorotrifluoroethylene(ECTFE)coating was applied to the surface of carbon steel through electrostatic spraying and low-temperature heat treatment.The morphology and structure of the coating were analyzed using various characterization techniques.The electrochemical data of the coated steel soaked in 3.5%(mass fraction)NaCl solution for 90 d at different periods were also examined.The findings indicate that the outer surface of the coating remains structurally stable before and after soaking.F can diffuse into the steel substrate,facilitating the bonding between the coating and the steel substrate,but the free F also induces a weakening effect on the crystalline structure.Due to the thickness of the coating edge and the susceptibility to infiltration of the corrosive medium,under-film micro-zone corrosion occurs at a slow rate.After soaking for 90 d,the impedance modulus measures approximately 10^(4)Ω·cm^(2),and the open circuit potential(OCP)is−0.61 V.The self-corrosion current density is 1.13×10^(−6)A/cm^(2),resulting in a calculated coating protection rate of 99.29%.In summary,despite edge corrosion occurring,the ECTFE coating provides excellent corrosion protection.

Numerical study on local failures of reinforced concrete slabs against underwater close-in explosions

Reinforced concrete(RC)slabs are the primary load-carrying member of underwater facilities.They can suffer severe local failures such as cratering,spalling,or breaching as a result of underwater close-in(UWCI)explosions.In this study,we established a fully validated high-fidelity finite element analysis approach to precisely reproduce the local failures of RC slabs after a UWCI explosion.A recently proposed dynamic constitutive model is used to describe wet concrete.The effects of free water content on the material properties,including the tensile/compressive strength,elastic modulus,strain rate effect,failure strength surface,and equation of state,are comprehensively calibrated based on existing test data.The calibrated material parameters are then verified by a single-element test.A high-fidelity finite element analysis(FEA)approach of an RC slab subjected to a UWCI explosion is established using an arbitrary Lagrangian-Eulerian(ALE)algorithm.Simulating previous UWCI explosion tests on RC orifice targets and underwater contact explosion tests on saturated concrete slabs showed that the established FEA approach could accurately reproduce the pressure-time history in water and damage patterns,including the cracking,cratering,and spalling,of the RC orifice target and saturated concrete slab.Furthermore,parametric studies conducted by simulating an RC slab subjected to a UWCI explosion showed that:(i)the local failure of an RC slab enlarges with increased charge weight,reduced standoff distance,and reduced structural thickness;(ii)compared to a water-backed RC slab,an air-backed RC slab exhibits much more obvious local and structural failure.Lastly,to aid the anti-explosion design of relevant underwater facilities,based on over 90 simulation cases empirical formulae are summarized to predict local failure modes,i.e.,no spall,spall,and breach,of water-and air-backed RC slabs subjected to a UWCI explosion.

Simultaneous determination of Repaglinide and Irbesartan in biological plasmas using micellar enhanced excitation-emission matrix fluorescence coupled with ATLD method

A highly sensitive and selective 3D excitation-emission fluorescence method has been proposed to rapidly quantify the combined antidiabetics Repaglinide(Re) and Irbesartan(Ir) in rat and human plasmas with the aid of second-order calibration method based on alternating trilinear decomposition(ATLD) method. Re and Ir with weak fluorescence can be endowed with strong fluorescent property by changing the microenvironment in samples and improving the fluorescence quantum yield by using an appropriate micellar enhanced surfactant. The enhanced excitation-emission matrix fluorescence of Re and Ir can be accurately resolved and can simultaneously attain the optimal concentration even in the presence of a potentially strong intrinsic fluorescence from complex biological matrices, such as rat and human plasmas, by using the ATLD method, which completely exploits the "second-order advantage". The average recoveries of Re and Ir obtained from ATLD with the factor number of 3(N=3) were 101.0%±4.3% and 99.1%±4.1% for rat plasma and 100.5%±5.4% and 97.1%±3.6% for human plasma. Several statistical methods, including Student's t-test, figures of merit, and elliptical joint confidence region, have been utilized to evaluate the accuracy of the proposed method. Results show that the developed method can maintain second-order advantage in simultaneous determinations of the weak fluorescent analytes of interest in different biological plasma matrices.

Compressive properties of a novel slurry-infiltrated fiber concrete reinforced with arc-shaped steel fibers

Slurry-infiltrated fiber concrete(SIFCON)is a sort of strain hardening cement-based composite material,typically made with 5%–20%steel fibers.This study focused on a novel type of SIFCON in which hooked-end steel fibers were replaced by arc-shaped steel fibers.The quasi-static compressive properties of the SIFCON were first measured.Test results suggested that using arc-shaped steel fibers in lieu of hooked-end steel fibers increased the quasi-static compressive strength by 47.1%and the strain at peak stress by 56.3%.We attribute these improvements to new crack-resisting mechanisms,namely“fiber crosslock”,“dual bridging”,and“confinement loops”,when the arc-shaped steel fibers are introduced into SIFCON.As high impact resistance is a special property of SIFCON that is of practical significance,the dynamic compressive properties of arc-shaped steel fiber SIFCON were studied by using an 80-mm-diameter split Hopkinson pressure bar(SHPB).The results showed that the dynamic compressive strength,dynamic increase factor(DIF),and dynamic toughness of SIFCON all increased with the strain rate.The SIFCON incorporating arc-shaped steel fibers proved to have significant advantages in structural applications requiring high impact resistance.

8种名优绿茶香气品质与其成分间协同定量组效关系研究

本文首先利用电子鼻(E-nose)结合偏最小二乘判别分析(PLSDA)成功判别了8种不同种类和等级的名优绿茶的香气品质.为进一步解释香气质量差异,借助局部极小值背景漂移校正、多尺度高斯平滑以及色谱保留时间校正法对名优绿茶的气相色谱-质谱联用(GC-MS)指纹图谱进行预处理,再利用移动窗口偏最小二乘回归(MWPLSR)将预处理后的指纹图谱与香气品质得分构建谱效关系模型,筛选出21种潜在特征香气物质,最后利用变量加权最小二乘支持向量机(PSO-VWLS-SVM)将特征香气物质的含量与不同绿茶香气质量得分相关联,根据各特征香气物质的贡献率,成功揭示了名优绿茶香气物质与香气品质之间的协同量-组效关系.本文提出的方法为绿茶特征香气品质标志物的筛查和其量效-组效关系研究提供了一种新的策略方法.

Neural progenitor diversity and their therapeutic potential for spinal cord repair

Development of the central nervous system(CNS)requires progressive differentiation of neural stem cells,which generate a variety of neural progenitors with distinct properties and differentiation potentials in a spatiotemporally restricted manner.The underlying mechanisms of neural progenitor diversification during development started to be unraveled over the past years.We have addressed these questions by v-myc immortaliza-tion method and generation of neural progenitor clones.These clones are served as in vitro models of neural differentiation and cellular tools for transplantation in animal models of neurological disorders including spinal cord injury.In this review,we will discuss features of two neural progenitor types(radial glia and GABAergic interneuron progenitor)and diversification even within each progenitor type.We will also discuss pathophysiol-ogy of spinal cord injury and our ongoing research to address both motor and sensory malfunctions by trans-plantation of these neural progenitors.