Crucial Role of P2X7 Receptor in Regulating Exocytosis of Single‐Walled Carbon Nanotubes in Macrophages

Exocytosis of single‐walled carbon nanotubes (SWCNTs) determines therapeutic efficiency and toxicity of nanoproducts but its underlying mechanism remains elusive. In this study, it is found that the exocytosis mechanism of SWCNTs is mediated mainly through the activation of P2X₇ receptor (P2X₇R), an ATP‐gated membrane receptor highly expressed in macrophages. Inhibition of P2X₇R signaling by either a specific inhibitor (oxidized ATP) or small interfering RNA targeting P2X₇R largely prevents the exocytosis of SWCNTs from Raw264.7 cells, resulting in significant accumulation of SWCNTs within cells. In contrast, activation of P2X₇R with ATP promotes exocytosis of SWCNTs. Specifically, it is elucidated that internalized SWCNTs are accumulated in lysosomes and induce transitional release of ATP into extracellular space, which further activates P2X₇R, leading to the influx of calcium ions, phosphorylation of protein kinase C, ERK1/2, p38, and JNK, as well as alkalization of lysosomes. SWCNTs exposure also induces microtubules reorganization that facilitates the secretion of SWCNTs‐containing lysosomes. It is also found that P2X₇R simultaneously mediates secretion of IL‐1β from Raw264.7 cells during the process of SWCNTs exocytosis. The combined data reveals that P2X₇R‐mediated pathway is the predominant molecular mechanism for exocytosis of SWCNTs in Raw264.7 cells. Moreover, SWCNT‐induced inflammation is closely coupled with the exocytosis of SWCNTs through P2X₇R.     

Inter‐endothelial Transport of Microvectors using Cellular Shuttles and Tunneling Nanotubes

New insights into the intra‐ and intercellular trafficking of drug delivery particles challenges the dogma of particles as static intracellular depots for sustained drug release. Recent discoveries in the cell‐to‐cell transfer of cellular constituents, including proteins, organelles, and microparticles sheds light on new ways to propagate signals and therapeutics. While beneficial for the dispersion of therapeutics at sites of pathologies, propagation of biological entities advancing disease states is less desirable. Mechanisms are presented for the transfer of porous silicon microparticles between cells. Direct cell‐to‐cell transfer of microparticles by means of membrane adhesion or using membrane extensions known as tunneling nanotubes is presented. Cellular relays, or shuttle cells, are also shown to mediate the transfer of microparticles between cells. These microparticle‐transfer events appear to be stimulated by environmental cues, introducing a new paradigm of environmentally triggered propagation of cellular signals and rapid dispersion of particle‐delivered therapeutics. The opportunity to use microparticles to study cellular transfer events and biological triggers that induce these events may aid in the discovery of therapeutics that limit the spread of disease.     

Engineered Macrophages: A Safe-by-Design Approach for the Tumor Targeting Delivery of Sub-5 nm Gold Nanoparticles

Ultrasmall nanoparticles (NPs) are a promising platform for the diagnosis and therapy of cancer, but the particles in sizes as small as several nanometers have an ability to translocate across biological barriers, which may bring unpredictable health risks. Therefore, it is essential to develop workable cell-based tools that can deliver ultrasmall NPs to the tumor in a safer manner. Here, this work uses macrophages as a shuttle to deliver sub-5 nm PEGylated gold (Au) NPs to tumors actively or passively, while reducing the accumulation of Au NPs in the brain. This work demonstrates that sub-5 nm Au NPs can be rapidly exocytosed from live macrophages, reaching 45.6% within 24 h, resulting in a labile Au NP-macrophage system that may release free Au NPs into the blood circulation in vivo. To overcome this shortcoming, two straightforward methods are used to engineer macrophages to obtain “half-dead” and “dead” macrophages. Although the efficiency of engineered macrophages for delivering sub-5 nm Au NPs to tumors is 2.2–3.8% lower than that of free Au NPs via the passive enhanced permeability and retention effect, this safe-by-design approach can dramatically reduce the accumulation of Au NPs in the brain by more than one order of magnitude. These promising approaches offer an opportunity to expand the immune cell- or stem cell-mediated delivery of ultrasmall NPs for the diagnosis and therapy of diseases in a safer way in the future.     

Cascade Delivery to Golgi Apparatus and On-Site Formation of Subcellular Drug Reservoir for Cancer Metastasis Suppression

As the foremost cause of cancer-related death, metastasis consists of three steps: invasion, circulation, and colonization. Only targeting one single phase of the metastasis cascade may be insufficient since there are many alternative routes for tumor cells to disseminate. Here, to target the whole cascade of metastasis, hybrid erythrocyte and tumor cell membrane-coated nanoparticle (Hyb-NP) is designed with dual functions of increasing circulation time and recognizing primary, circulating, and colonized tumors. After loading with monensin, a recently reported metastasis inhibitor, the delivery system profoundly reduces spontaneous metastasis in an orthotopic breast cancer model. Underlying mechanism studies reveal that Hyb-NP can deliver monensin to its action site in the Golgi apparatus, and in return, monensin can block the exocytosis of Hyb-NP from the Golgi apparatus, forming a reservoir-like subcellular structure. Notably, the Golgi apparatus reservoir displays three vital functions for suppressing metastasis initialization, including enhanced subcellular drug retention, metastasis-related cytokine release inhibition, and directional migration inhibition. Collectively, based on metastasis cascade targeting at the tissue level, further formation of the Golgi apparatus drug reservoir at the subcellular level provides a potential therapeutic strategy for cancer metastasis suppression.     

Physicochemical Properties and Route of Systemic Delivery Control the In Vivo Dynamics and Breakdown of Radiolabeled Gold Nanostars

The in vivo dynamics of nanoparticles requires a mechanistic understanding of multiple factors. Here, for the first time, the surprising breakdown of functionalized gold nanostars (F-AuNSs) conjugated with antibodies and ⁶⁴Cu radiolabels in vivo and in artificial lysosomal fluid ex vivo, is shown. The short-term biodistribution of F-AuNSs is driven by the route of systemic delivery (intravenous vs intraperitoneal) and long-term fate is controlled by the tissue type in vivo. In vitro studies including endocytosis pathways, intracellular trafficking, and opsonization, are combined with in vivo studies integrating a milieu of spectroscopy and microcopy techniques that show F-AuNSs dynamics is driven by their physicochemical properties and route of delivery. F-AuNSs break down into sub-20 nm broken nanoparticles as early as 7 days postinjection. Martini coarse-grained simulations are performed to support the in vivo findings. Simulations suggest that shape, size, and charge of the broken nanoparticles, and composition of the lipid membrane depicting various tissues govern the interaction of the nanoparticles with the membrane, and the rate of translocation across the membrane to ultimately enable tissue clearance. The fundamental study addresses critical gaps in the knowledge regarding the fate of nanoparticles in vivo that remain a bottleneck in their clinical translation.     

Drug delivery: Logic‐Embedded Vectors for Intracellular Partitioning,Endosomal Escape,and Exocytosis of Nanoparticles (Small 23/2010)

A new generation of nanocarriers, logic‐embedded vectors (LEVs), is endowed with the ability to localize components at multiple intracellular sites, thus creating an opportunity for synergistic control of redundant or dual‐hit pathways. LEV encoding elements include size, shape, charge, and surface chemistry. In this study, LEVs consist of porous silicon nanocarriers, programmed for cellular uptake and trafficking along the endosomal pathway, and surface‐tailored iron oxide nanoparticles, programmed for endosomal sorting and partitioning of particles into unique cellular locations. In the presence of persistent endosomal localization of silicon nanocarriers, amine‐functionalized nanoparticles are sorted into multiple vesicular bodies that form novel membrane‐bound compartments compatible with cellular secretion, while chitosan‐coated nanoparticles escape from endosomes and enter the cytosol. Encapsulation within the porous silicon matrix protects these nanoparticle surface‐tailored properties, and enhances endosomal escape of chitosan‐coated nanoparticles. Thus, LEVs provide a mechanism for shielded transport of nanoparticles to the lesion, cellular manipulation at multiple levels, and a means for targeting both within and between cells.     

The influence of the polarization of the radiation on the accuracy of the transmission of the dimensions of the unit of temperature in radiation thermometry

The results of an investigation of different types of tungsten lamps in order to estimate the components of the error budget of spectrum-pyrometer apparatus are presented. Quantitative relations are considered and the results of experimental research, which enable systematic methods to be developed for eliminating the influence of polarization of the radiation of the lamps in standard radiation thermometry, are analyzed.Translated from Izmeritelnaya Tekhnika, No. 9, pp. 42–45, September, 2004.     

贮槽液位测量单片机应用系统

本文研究用８０９８单片机对密闭大贮槽的贮液容量进行自动检测的应用系统，解决了把贮槽液位测量传感器输出的电流信号直接转换成贮液重量进行显示，从而使显示直观、清晰．     

降低反渗透设备出水电导率的方法

反渗透设备是水处理行业常用设备,广泛用于纯水、高纯水等的预处理.通过试验,找到两种降低反渗透设备出水电导率的方法:反渗透设备进水软化后加碱和反渗透设备进水酸化后脱气,这两种方法都有一定的应用范围,应根据工艺要求和运行费用选择使用.     

Increasing the Reliability of the Primary Processing of the Results of Measurements

A new approach is considered to processing the results of measurements. It is utilized as a basis for carrying out primary processing including the detection and elimination of anomalous measurements and also for cleansing results of additive noise components. The results are presented of an analysis of the efficiency of a method for multiplying estimates when cleansing the results of measurements of additive noise components.     

论人工科学、人居环境科学、事理学的同一性

目的 辨析"人工科学""人居环境科学""事理学"的本质属性和共性特征,并探讨新时代背景下设计学科理论体系建设的可能性方向.方法 首先,采取文献法,回溯人工科学、人居环境科学和事理学的提出及其相关成果,并借助VOSviewer工具分析三者在国内的发展状况,重在厘清理论脉络、理论应用及其对学界和业界产生的不同程度的影响;其次,运用比较法,分别从研究内容、研究思维、研究途径三个维度逐一展开,重在总结三者在认识论、方法论等层面的特性与共性.结论 人工科学、人居环境科学、事理学在学理上具有同一性,可将"人工科学"作为世界设计学科共性基础理论之一,将"人居环境科学""事理学"视为世界设计理论中的"中国智慧"和"中国方案".     

表面活性剂在处理太安表面静电中的应用

通过实验检验表面活性剂对太安表面静电积累的降解效果,测定表面活性剂对太安基本性质的影响,分析比较对表面活性剂的优化选择。     

近红外技术应用于成品卷烟的内在质量稳定性控制

以某品牌卷烟为例,采用傅立叶变换近红外光谱技术采集成品卷烟的近红外光谱,结合连续流动法测定样品中还原糖、烟碱、氯、钾含量的数据,采用偏最小二乘法(PLS)分别建立了预测品牌卷烟烟丝中还原糖、烟碱、氯、钾及糖碱比、钾氯比的近红外模型,模型的相关系数(除钾外)都在0.95以上。用建立的模型快速检测红狼卷烟的各化学成分,通过值的波动范围初步监控成品的质量稳定性。并采集它们的近红外光谱,应用连续小波变换(CWT)对原始光谱进行预处理,再对CWT系数进行主成分分析(PCA),在PCA分析的基础上引入马氏距离算法建立成品卷烟质量稳定性评价模型。通过研究光谱预处理对卷烟样品分类鉴别的影响,确定马氏距离阈值Dthro,结合近红外定量测定值与马氏距离阈值Dthro,对卷烟产品质量稳定性进行评价和控制。     

公立高校两权分离的现实基础与动力机制分析

市场经济体制下，利用市场机制配置资源及政事分离是我国公立高校面临的迫切要求。而这一要求得以付诸实践的前提之一就是实行高校所有权和经营权的分离。文章认为，当前我国公立高校两权分离是不彻底的,并指出高校的所有权和经营权存在分离的现实基础以及高校与市场、高校与政府间矛盾生成的动力机制，这些决定了两权分离将成为高校未来发展的合理方向。