Effects of the Anti-Tumorigenic Agent AT101 on Human Glioblastoma Cells in the Microenvironmental Glioma Stem Cell Niche

Glioblastoma (GBM) is a barely treatable disease due to its profound chemoresistance. A distinct inter- and intratumoral heterogeneity reflected by specialized microenvironmental niches and different tumor cell subpopulations allows GBMs to evade therapy regimens. Thus, there is an urgent need to develop alternative treatment strategies. A promising candidate for the treatment of GBMs is AT101, the R(-) enantiomer of gossypol. The present study evaluates the effects of AT101, alone or in combination with temozolomide (TMZ), in a microenvironmental glioma stem cell niche model of two GBM cell lines (U251MG and U87MG). AT101 was found to induce strong cytotoxic effects on U251MG and U87MG stem-like cells in comparison to the respective native cells. Moreover, a higher sensitivity against treatment with AT101 was observed upon incubation of native cells with a stem-like cell-conditioned medium. This higher sensitivity was reflected by a specific inhibitory influence on the p-p42/44 signaling pathway. Further, the expression of CXCR7 and the interleukin-6 receptor was significantly regulated upon these stimulatory conditions. Since tumor stem-like cells are known to mediate the development of tumor recurrences and were observed to strongly respond to the AT101 treatment, this might represent a promising approach to prevent the development of GBM recurrences.     

近源成藏——来自鄂尔多斯盆地延长组湖盆东部“边缘”延长组6段原油的地球化学证据

延安以东和以北的鄂尔多斯盆地东北部地区曾被认为位处三叠纪延长组7段（长7段）沉积期古湖盆的"边缘"，一些学者认为该区延长组烃源岩不发育，因而其油藏原油系湖盆中心生成的原油经长距离侧向运移而来；但也有研究认为，包括盆地边缘在内的整个鄂尔多斯盆地致密油藏均为近源成藏。为明确盆地东部地区延长组原油来源，对三叠纪湖盆"东缘"七里村油田的主力油层延长组6段（长6段）原油开展了原油地球化学和油源对比研究。七里村油田长6段原油具有高饱和烃、高饱芳比、低非烃和低沥青质的特征，正构烷烃呈前高单峰型，主峰碳为C₁₉，生物标志化合物分析显示长6段原油为同源成熟原油，生油母质以藻类等低等水生生物为主，混有陆源高等植物，母源沉积环境为偏还原性的淡水湖泊。七里村油田长6段原油与本地区长7段黑色泥页岩和暗色泥岩2种烃源岩均具有明显亲缘关系，而与志丹、富县等湖盆中心地区的长7段烃源岩在族组成、生物标志化合物和稳定碳同位素特征上均存在明显区别。综合分析认为七里村油田长6段原油并非湖盆中心长7段优质烃源岩所生油气经长距离运移而来，而主要为原位长7段烃源岩生成的原油经垂向运移和短距离侧向运移在长6段等储层中聚集成藏，属于近源成藏。     

Role of the HSP70 Co-Chaperone SIL1 in Health and Disease

Cell surface and secreted proteins provide essential functions for multicellular life. They enter the endoplasmic reticulum (ER) lumen co-translationally, where they mature and fold into their complex three-dimensional structures. The ER is populated with a host of molecular chaperones, associated co-factors, and enzymes that assist and stabilize folded states. Together, they ensure that nascent proteins mature properly or, if this process fails, target them for degradation. BiP, the ER HSP70 chaperone, interacts with unfolded client proteins in a nucleotide-dependent manner, which is tightly regulated by eight DnaJ-type proteins and two nucleotide exchange factors (NEFs), SIL1 and GRP170. Loss of SIL1′s function is the leading cause of Marinesco-Sjögren syndrome (MSS), an autosomal recessive, multisystem disorder. The development of animal models has provided insights into SIL1′s functions and MSS-associated pathologies. This review provides an in-depth update on the current understanding of the molecular mechanisms underlying SIL1′s NEF activity and its role in maintaining ER homeostasis and normal physiology. A precise understanding of the underlying molecular mechanisms associated with the loss of SIL1 may allow for the development of new pharmacological approaches to treat MSS.     

Functional Inactivation of Drosophila GCK Orthologs Causes Genomic Instability and Oxidative Stress in a Fly Model of MODY-2

Maturity-onset diabetes of the young (MODY) type 2 is caused by heterozygous inactivating mutations in the gene encoding glucokinase (GCK), a pivotal enzyme for glucose homeostasis. In the pancreas GCK regulates insulin secretion, while in the liver it promotes glucose utilization and storage. We showed that silencing the Drosophila GCK orthologs Hex-A and Hex-C results in a MODY-2-like hyperglycemia. Targeted knock-down revealed that Hex-A is expressed in insulin producing cells (IPCs) whereas Hex-C is specifically expressed in the fat body. We showed that Hex-A is essential for insulin secretion and it is required for Hex-C expression. Reduced levels of either Hex-A or Hex-C resulted in chromosome aberrations (CABs), together with an increased production of advanced glycation end-products (AGEs) and reactive oxygen species (ROS). This result suggests that CABs, in GCK depleted cells, are likely due to hyperglycemia, which produces oxidative stress through AGE metabolism. In agreement with this hypothesis, treating GCK-depleted larvae with the antioxidant vitamin B6 rescued CABs, whereas the treatment with a B6 inhibitor enhanced genomic instability. Although MODY-2 rarely produces complications, our data revealed the possibility that MODY-2 impacts genome integrity.     

NNI-1型C_5/C_6烷烃异构化催化剂长周期运行分析及建议

中国石化海南炼油化工有限公司0.2 Mt/a C5/C6烷烃异构化装置以连续重整装置的拔头油为原料,使用NNI-1催化剂,采用一次通过流程,不设脱异戊烷塔和稳定塔,经设在连续重整装置内的脱丁烷塔稳定处理后作为汽油调合组分。该装置于2006年9月开工投产,截至2015年3月已连续运行3个周期。长周期运行分析结果表明:前两个周期中NNI-1催化剂具有较高的异构化活性及选择性,C5异构化率为60%左右,C6异构化率为80%左右,C6选择性为15%左右,产品辛烷值基本达到技术指标要求(RON≥78);而在第三周期运行中,催化剂积炭增加等原因导致其异构化活性及选择性降低,异构化产品辛烷值提升能力呈现逐步衰减的趋势,提高反应苛刻度已不能弥补催化剂活性下降造成的产品辛烷值降低。为保证装置长周期运行,建议择机停工对催化剂进行再生,或是直接换用与装置原料性质匹配的异构化催化剂。     

Heat propagation in thermally conductive polymers of PA6 and hexagonal boron nitride

Thermally conductive polymers offer new possibilities for the heat dissipation in electric and electronic components, for example, by a three‐dimensional shaping of the heat sinks. To face safety regulations, improved fire performance of those components is required. In contrast to unfilled polymers, those materials exhibit an entirely different thermal behavior. To investigate the flammability, a phosphorus flame retardant was incorporated into thermally conductive composites of polyamide 6 and hexagonal boron nitride. The flame retardant decreased the thermal conductivity only slightly. However, the burning behavior changed significantly, due to a different heat propagation, which was investigated using a thermographic camera. An optimum content of hexagonal boron nitride for a sufficient thermal conductivity and fire performance was found between 20 and 30 vol%. The improvement of the fire performance was due to a faster heat release out of the pyrolysis zone and an earlier decomposition of the flame retardant. For higher contents of hexagonal boron nitride, the heat was spread faster within the part, promoting an earlier ignition and increasing the decomposition rate of the flame retardant.     

The formation of fibrous structure of polyamide 6 induced by the three-step forming process and its prominent reinforcement in nitrile rubber

Nitrile rubber (NBR) blends with excellent performance have always been a hot research topic in petroleum field. Due to the excellent performance and compatibility of polyamide 6 (PA6), it provides an opportunity for the preparation of high-performance NBR/PA6 blends. In this article, NBR/PA6 blends were prepared by the three-step molding process. Experimentally, it was found that PA6 has a prominent reinforcement effect in NBR matrix. The variation of this mechanical property was investigated from different aspects of the crystal structure, crystallinities, phase morphology, and so on. It can be cleared that the formation of fibrous structure of PA6 phase is the main factor for reinforcement of the polymer blends. Meanwhile, the formation mechanism of the special phase structure induced by the three-step process is deeply expounded and its structural evolution schematic is established. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47472.     

基于“IPv6+”的智能IP网络方案

随着第4次工业革命的到来，人类社会正逐步迈向万物互联的智能时代。智能时代需要更加自动化、智能化的IP网络，基于“IPv6+”的SRv6、BIERv6等技术是使能新一代IP网络的关键基础。全面阐述了“IPv6+”的技术内涵，结合华为在智能 IP 网络解决方案上的创新和思考，介绍了“IPv6+”在极简连接、SLA 保障、专网体验、质量感知和云网一体等多个解决方案场景的关键技术与典型应用，助力5G与云业务发展。     

两种3D打印用雾化Ti-6Al-4V粉末的对比研究

本研究分别利用水冷铜坩埚真空感应熔炼气雾化(VIGA-CC)和等离子旋转电极(PREP)两种技术制备出球形Ti-6Al-4V合金粉末,作者利用SEM、同步辐射CT扫描-三维重建和氩气含量测试等分析手段对不同粒径的Ti-6Al-4V合金粉末的孔洞缺陷和氩气含量、硬度值进行了表征。实验结果表明, VIGA-CC粉末粒度分布宽,细粉收得率较多,粉末粒度分布在40~180 μm之间, PREP粉末的粒度分布较窄,主要集中在110~180 μm之间；金属粉末内部的孔隙率、气体含量和孔尺寸随着粉末粒度的增大而增大,且同一粒径范围内VIGA-CC粉末的气孔概率多于PREP粉末；随着粉末粒径减小,粉末截面组织逐渐细化,其硬度值逐渐升高,整体上VIGA-CC粉末硬度值高于PREP粉末。     

Omega-6支撑身体，Omega-3支撑大脑：均衡摄入对儿童大脑发育的影响（网络首发、推荐阅读）

人体大脑和身体的发育，需要从食物中摄取均衡的营养物质。人类大脑是区分人类和其他动物的特征。食物中的必需脂肪酸是机体组织结构和功能的必要组成部分。Omega-6（O6）亚油酸（LA6）是皮肤组织的组成成分，且是炎症、血栓形成、免疫和其他信号分子的前体；Omega-3（O3）α-亚麻酸（ALA3），特别是其长链代谢产物——二十二碳六烯酸（DHA3），是大脑、视网膜和部分神经组织中的关键组分。从富含LA6脂肪酸（缺乏O3脂肪酸）的植物籽中提取出的廉价而优质油脂，是20世纪的西方国家食品工业生产的主要脂肪来源。在代谢通路中，高浓度的LA6脂肪酸可拮抗O3脂肪酸代谢，造成O3脂肪酸不足，因此，在给怀孕动物的饲料中，只提供富含LA6但缺乏O3脂肪酸的油脂作为唯一的脂肪来源，会导致幼崽大脑发育不良。过去20~30年的研究表明，低含量LA6且含DHA3的油脂可改善大脑的功能。近年来的研究较多集中在营养因素对大脑发育的影响，最新研究数据表明，脂肪酸平衡对营养不良儿童的大脑发育尤为重要。世界卫生组织（WHO）越来越重视大脑的营养健康，通过其下属的食品法典委员会，建议用于治疗严重急性营养不良儿童的即食治疗食品中，使用含有均衡脂肪酸组成/构成的脂肪。同样，脂肪酸均衡对老年人可能也很重要。目前，业界已经有了调整油脂成分的方法，以确保脂肪酸均衡，从而维持人体整个生命周期的大脑健康。