A Novel LRRK2 Variant p.G2294R in the WD40 Domain Identified in Familial Parkinson’s Disease Affects LRRK2 Protein Levels

Leucine-rich repeat kinase 2 (LRRK2) is a major causative gene of late-onset familial Parkinson’s disease (PD). The suppression of kinase activity is believed to confer neuroprotection, as most pathogenic variants of LRRK2 associated with PD exhibit increased kinase activity. We herein report a novel LRRK2 variant—p.G2294R—located in the WD40 domain, detected through targeted gene-panel screening in a patient with familial PD. The proband showed late-onset Parkinsonism with dysautonomia and a good response to levodopa, without cognitive decline or psychosis. Cultured cell experiments revealed that p.G2294R is highly destabilized at the protein level. The LRRK2 p.G2294R protein expression was upregulated in the patient’s peripheral blood lymphocytes. However, macrophages differentiated from the same peripheral blood showed decreased LRRK2 protein levels. Moreover, our experiment indicated reduced phagocytic activity in the pathogenic yeasts and α-synuclein fibrils. This PD case presents an example wherein the decrease in LRRK2 activity did not act in a neuroprotective manner. Further investigations are needed in order to elucidate the relationship between LRRK2 expression in the central nervous system and the pathogenesis caused by altered LRRK2 activity.     

OBE-CDIO理念下“集成电路版图分析与设计”课程教学改革与探索

针对目前集成电路版图分析与设计课程存在教学方法老化、教学模式形式化等问题,本文以OBE-CDIO教育理念为指导,对”集成电路版图分析与设计”课程的课程教学模式、课程设计、项目式教学方式和课程考核方式等方面的改革进行有益的探索与实践。将工程教学认证中对学生的专业毕业要求作为制定教学目标的依据,将BB网络平台、ISO9001等现代化教学资源和质量标准融入课堂教学,采用OBE-CDIO能力教学理念指导课程设计,实现教学环节与考核环节的科学化与多元化,通过引入课程思政激发学生学习热情,树立社会主义核心价值观,全面地培养学生的综合版图分析与设计能力和素养。     

Marine Phospholipids from Fishery By-Products Attenuate Atherosclerosis

In this study, the anti-atherosclerotic properties of three marine phospholipids (MPLs) extracts from fishery by-products including codfish roe, squid gonad, and shrimp head are verified. Their effects on key factors involved in atherosclerosis are examined and compared to explore whether the differences in their constitutions lead to the differences in the function. All three MPLs dampen oxidation of low- density lipoproteins (LDL) in vitro. Treating RAW264.7 macrophages and HUVECs endothelial cells with each MPLs ranging 10–100 µg mL⁻¹ does not decrease cell viability, yet ox-LDL caused cytotoxicity of both cells are alleviated by 50 or 100 µg mL⁻¹ MPLs treatment. In addition, the three MPLs reduce ox-LDL induced macrophage foam-like transition, mainly through inhibition of lipid uptake. Of the three MPLs, the one from squid gonad exhibits the best effect. On the other hand, all three MPLs modulate inflammatory responses, equally, by inhibiting the adhesion of monocytes to endothelial cells, and decreasing secretion of pro-inflammatory cytokines IL-6 and MCP-1. Using a high-cholesterol diet induced zebrafish model, it is found that all three MPLs, especially the one from squid gonad, alleviates cholesterol accumulation in early plaques, and decreases total cholesterol as well as lipid peroxide in vivo. Practical Applications: As a way of making the best of the increasingly scarce marine resources, valuable lipid components can be recovered from by-products and wastes from the fishery industry. Here, we tested the anti-atherosclerotic effects and the mechanisms of three MPLs extracted from codfish roe, squid gonad, and shrimp head. Our study provides further evidence that marine phospholipids extracted from fishery by-products could protect against atherosclerosis, and helps to elucidate the structure-function relationship of MPLs.     

下扬子地区下志留统风暴沉积特征及风暴作用对泥页岩品质的影响

近年来在下扬子地区页岩气地质调查井所获取的地层岩心资料，揭示该地区下志留统风暴沉积较为发育。基于精细的岩心观察描述，详细分析了下扬子地区下志留统高家边组下段中上部风暴沉积的特征，并阐明了风暴作用对泥页岩的影响。研究表明：研究区风暴岩岩性偏细，以粉砂岩为主，石英含量较高，结构成熟度较低，具2种不同的粒度概率曲线；主要发育底部冲刷面、块状层理、平行层理、丘状交错层理、波纹交错层理、准同生变形构造等沉积构造；垂向上主要识别出4种风暴沉积序列，均具有从底到顶粒度变细的沉积特征，不同的沉积序列与风暴流能量的强弱有关。下扬子地区早志留世频繁的风暴活动与研究区的古地理背景和古气候条件具有内在联系。特大型风暴对浅海陆棚深水区的细粒泥质沉积物特征产生重要影响，包括降低有机质含量、减少单层厚度、破坏垂向连续性、改变原始沉积构造和侧向稳定性等，总体上降低了泥页岩的品质。因此，研究认为在页岩气的勘探和评价过程中应重视风暴因素对陆棚深水区原始泥质沉积物的影响。     

Tactile colour pictogram to improve artwork appreciation of people with visual impairments

A recent development in tactile technology enables an improvement in the appreciation of the visual arts for people with visual impairment (PVI). The tactile sense, in conjunction with, or a possibly as an alternative to, the auditory sense, would allow PVIs to approach artwork in a more self‐driven and engaging way that would be difficult to achieve with just an auditory stimulus. Tactile colour pictograms (TCPs), which are raised geometric patterns, are ideographic characters that are designed to enable PVIs to identify colours and interpret information by touch. In this article, three TCPs are introduced to code colours in the Munsell colour system. Each colour pattern consists of a basic cell size of 10 mm × 10 mm to represent the patterns consistently in terms of regular shape. Each TCP consists of basic geometric patterns that are combined to create primary, secondary, and tertiary colour pictograms of shapes indicating colour hue, intensity and lightness. Each TCP represents 29 colours including six hues; they were then further expanded to represent 53 colours. Two of them did not increase the cell size, the other increased the cell size 1.5 times for some colours, such as yellow‐orange, yellow, blue, and blue‐purple. Our proposed TCPs use a slightly larger cell size compared to most tactile patterns currently used to indicate colour, but code for more colours. With user experience and identification tests, conducted with 23 visually impaired adults, the effectiveness of the TCPs suggests that they were helpful for the participants.     

基于乙酰胆碱酯酶和氧化应激研究海胆酮对阿尔茨海默症的作用机制

海胆酮是一种酮式类胡萝卜素，主要从海胆及藻类等海洋生物中提取。本文研究海胆酮对乙酰胆碱酯酶（acetylcholinesterase，AChE）的抑制作用，应用酶动力学、荧光光谱、圆二色光谱和分子对接技术研究海胆酮对AChE的抑制机理，并用淀粉样β蛋白片段25～35（amyloid beta-peptide 25-35，Aβ25-35）诱导大鼠肾上腺嗜铬细胞瘤细胞（PC12细胞）建立阿尔茨海默症（Alzheimer’s disease，AD）模型，研究海胆酮对AD细胞模型氧化应激损伤的作用。结果表明，海胆酮有很强的AChE抑制活性，其半抑制质量浓度为（16.29±0.97）μg/mL，抑制常数Ki为3.82 μg/mL，表现为竞争性抑制；海胆酮可诱导AChE二级结构改变，更容易与AChE活性中心氨基酸Ser200、His440、Trp84和Tyr121结合，阻碍底物碘代硫代乙酰胆碱（acetylthiocholine iodide，ATCI）与酶结合，从而引起酶活力降低。海胆酮能有效抑制Aβ25-35诱导PC12细胞的AChE活力，降低丙二醛含量，增加超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶活力，减轻Aβ25-35诱导的PC12细胞氧化应激损伤。本研究基于AChE和氧化应激阐明了海胆酮对AD的潜在作用机制，为海胆酮在功能食品、生物医药等领域的应用提供了数据支持和理论根据。