The Contribution of Small Vessel Disease to Neurodegeneration: Focus on Alzheimer’s Disease,Parkinson’s Disease and Multiple Sclerosis

Brain small vessel disease (SVD) refers to a variety of structural and functional changes affecting small arteries and micro vessels, and manifesting as white matter changes, microbleeds and lacunar infarcts. Growing evidence indicates that SVD might play a significant role in the neurobiology of central nervous system (CNS) neurodegenerative disorders, namely Alzheimer’s disease (AD) and Parkinson’s disease (PD), and neuroinflammatory diseases, such as multiple sclerosis (MS). These disorders share different pathophysiological pathways and molecular mechanisms (i.e., protein misfolding, derangement of cellular clearance systems, mitochondrial impairment and immune system activation) having neurodegeneration as biological outcome. In these diseases, the actual contribution of SVD to the clinical picture, and its impact on response to pharmacological treatments, is not known yet. Due to the high frequency of SVD in adult-aged patients, it is important to address this issue. In this review, we report preclinical and clinical data on the impact of SVD in AD, PD and MS, with the main aim of clarifying the predictability of SVD on clinical manifestations and treatment response.     

Small Noncoding RNAs in Knee Osteoarthritis: The Role of MicroRNAs and tRNA-Derived Fragments

Knee osteoarthritis (OA) is a degenerative knee joint disease that results from the breakdown of joint cartilage and underlying bone, affecting about 3.3% of the world’s population. As OA is a multifactorial disease, the underlying pathological process is closely associated with genetic changes in articular cartilage and bone. Many studies have focused on the role of small noncoding RNAs in OA and identified numbers of microRNAs that play important roles in regulating bone and cartilage homeostasis. The connection between other types of small noncoding RNAs, especially tRNA-derived fragments and knee osteoarthritis is still elusive. The observation that there is limited information about small RNAs different than miRNAs in knee OA was very surprising to us, especially given the fact that tRNA fragments are known to participate in a plethora of human diseases and a portion of them are even more abundant than miRNAs. Inspired by these findings, in this review we have summarized the possible involvement of microRNAs and tRNA-derived fragments in the pathology of knee osteoarthritis.     

Supramolecular Nanofibers from Collagen-Mimetic Peptides Bearing Various Aromatic Groups at N-Termini via Hierarchical Self-Assembly

Self-assembly of artificial peptides has been widely studied for constructing nanostructured materials, with numerous potential applications in the nanobiotechnology field. Herein, we report the synthesis and hierarchical self-assembly of collagen-mimetic peptides (CMPs) bearing various aromatic groups at the N-termini, including 2-naphthyl, 1-naphtyl, anthracenyl, and pyrenyl groups, into nanofibers. The CMPs (R-(GPO)_n: n > 4) formed a triple helix structure in water at 4 °C, as confirmed via CD analyses, and their conformations were more stable with increasing hydrophobicity of the terminal aromatic group and peptide chain length. The resulting pre-organized triple helical CMPs showed diverse self-assembly into highly ordered nanofibers, reflecting their slight differences in hydrophobic/hydrophilic balance and configuration of aromatic templates. TEM analysis demonstrated that 2Np-CMP_n (n = 6 and 7) and Py-CMP₆ provided well-developed natural collagen-like nanofibers and An-CMP_n (n = 5–7) self-assembled into rod-like micelle fibers. On the other hand, 2Np-CMP₅ and 1Np-CMP₆ were unable to form nanofibers under the same conditions. Furthermore, the Py-CMP₆ nanofiber was found to encapsulate a guest hydrophobic molecule, Nile red, and exhibited unique emission behavior based on the specific nanostructure. In addition to the ability of CMPs to bind small molecules, their controlled self-assembly enables their versatile utilization in drug delivery and wavelength-conversion nanomaterials.     

An Autophagy-Disrupting Small Molecule Promotes Cancer Cell Death via Caspase Activation

A novel autophagy inhibitor, autophazole (Atz), which promoted cancer cell death via caspase activation, is described. This compound was identified from cell-based high-content screening of an imidazole library. The results showed that Atz was internalized into lysosomes of cells where it induced lysosomal membrane permeabilization (LMP). This process generated nonfunctional autolysosomes, thereby inhibiting autophagy. In addition, Atz was found to promote LMP-mediated apoptosis. Specifically, LMP induced by Atz caused release of cathepsins from lysosomes into the cytosol. Cathepsins in the cytosol cleaved Bid to generate tBid, which subsequently activated Bax to induce mitochondrial outer membrane permeabilization (MOMP). This event led to cancer cell death via caspase activation. Overall, the findings suggest that Atz will serve as a new chemical probe in efforts aimed at gaining a better understanding of the autophagic process.     

一种消除小直径管道焊接应力技术的数值分析

小直径管道的应力腐蚀问题一直是工程界较难解决的问题，作者针对这一难题，提出了一种新型的消除应力方法——温差形变处理技术。利用MSC．Marc大型通用非线性有限元分析软件，对小直径管道环缝焊接接头的原始残余应力及温差形变法消除残余应力进行了有限元模拟，得到了一系列关于加热位置、加热宽度和加热持续时间的数据和规律。结果表明，采用温差形变处理技术，在内外表面的焊缝处都可以得到零值左右的残余应力，从而为进一步的试验分析工作和工程应用奠定了基础。     

饰品金合金微量添加元素研究现状

从提高强度、防止氧化、提高铸造性能以及细化晶粒几个方面综述了饰品金合金中微量添加元素的一些研究现状。对不同微量添加元素对饰品金合金性能的影响、相应的副作用,作用机理以及加入量的确定等方面进行了综合评述。并对饰品金合金微量添加元素的发展进行了展望。     

小冲孔蠕变试验技术

小冲孔蠕变试验技术是获取在役构件蠕变性能的一种新方法，由于它具有接近无损取样的特点，因此受到学术界和工业界的广泛重视。本文简要回顾了小冲孔蠕变试验技术的发展及应用，重点介绍了典型小冲孔蠕变试验装置的组成及结构，指出了小冲孔蠕变试验技术目前存在的问题和广阔的应用前景。     

含Li的Al-Zn-Mg-Cu合金沉淀析出过程的定量分析

应用小角度X射线散射技术结合TEM分析定量的描述Al-Zn-Mg-Cu-Li合金时效过程中析出相尺寸分布和形貌等信息。通过分析确定合金在几种时效状态下析出相为轴比在0．2～0．4之间的扁回转椭球形。确定了析出相特征尺寸的对数正态分布和质量依回转半径的Maxwell分布。并分析分布曲线随动力强度Ks的变化特征，可以看出，析出相尺寸和质量分布曲线基本满足随动力强度增加，几何平均值增加，分布范围变宽。     

中国铝型材企业如何适应未来的市场需求

介绍了目前我国铝型材的市场状况，指出中国铝型材企业未来的市场状况将与日本15年前的市场状况相似，也指出了我国型材企业目前与先进国家的差距及如何赶上的措施。     

细丝窄间隙埋弧焊工艺参数寻优

主要研究A105钢小直径焊丝埋弧焊时,电弧电压、焊接电流和焊接热输入对焊缝成形的影响.在反复调节不同焊接工艺参数进行平板表面堆焊试验的基础上,得出保证最佳焊缝成形时,电弧电压与焊接电流的关系,以及它们的最佳匹配值,并量化了焊接热输入与焊缝宽度之间的关系.为窄间隙埋弧焊提供了有益的经验,同时也为小直径焊丝焊接工艺的全面优化奠定基础.