生存轨道与集值映象的不动点

基于无穷维空间中的生存定理，我们研究了集值映象的不动点，得到了一个新的不动点定理，推广和改进了[1]和[5]中的相应结果。     

Changes in the Laser-Induced Fluorescence Spectrum of Myocardium Tissue with Decrease in Its Viability

We investigated the laser-induced fluorescence spectra (LIF) of porcine cardiac tissues with different degrees of viability. The data obtained are compared with the results of routine histological investigations and also with the experiments performed with the use of fluorescent probes. It has been found with a high degree of reliability that the loss of the viability of the myocardium tissue leads to the alteration of its LIF spectra. This can be used for low-invasive rapid control of transplant viability in the process of its preparation and during surgery.     

Impact of proliferation strategies on food web viability in a model with closed nutrient cycle

A food web model with a closed nutrient cycle is presented and analyzed via Monte Carlo simulations. The model consists of three trophic levels, each of which is populated by animals of one distinct species. While the species at the intermediate level feeds on the basal species, and is eaten by the predators living at the highest level, the basal species itself uses the detritus of animals from higher levels as the food resource. The individual organisms remain localized, but the species can invade new lattice areas via proliferation. The impact of different proliferation strategies on the viability of the system is investigated. From the phase diagrams generated in the simulations it follows that in general a strategy with the intermediate level species searching for food is the best for the survival of the system. The results indicate that both the intermediate and top level species play a critical role in maintaining the structure of the system.     

Assessment of the in vitro toxicity of calixarenes and a metal-seamed calixarene: a chemical pathway for clinical application

Calixarenes are known to form host–guest complexes and supramolecular nanoassemblies with well-defined architectures. However, the use of these materials in conjunction with drug moieties is still under explored. One reason is the insufficient biocompatibility studies. Our present study represents a systematic in vitro investigation of the cytotoxicity associated with C-methylresorcin[4]arene, C-methylpyrogallol[4]arene, p-phosphonated calix[8]arene and a metal-seamed calixarene–copper(II) complex, using human HEK293 and rat C6G cell lines and two different cell viability assays (MTT and CellTiter-Glo) to avoid species-biased results. All compounds showed low to moderate toxicity. The trend in the CC₅₀ values indicated that the suppression of the coordination ability and the presence of phosphonate groups decrease the overall cytotoxicity of the compounds. The results of this study not only establish calixarenes and their immediate families as potential drug carriers and drug modifiers, but also reveal a pathway for fine-tuning their toxicological behaviour by appropriate chemical modification.     

Blood Proteins Strongly Reduce the Mobility of Artificial Self‐Propelled Micromotors

Autonomous self‐propelled catalytic microjets are envisaged as an important technology in biomedical applications, including drug delivery, micro/nanosurgery, and active dynamic bioassays. The direct in vivo application of these microjets, specifically in blood, is however impeded by insufficient knowledge on the in vivo viability of the technique. This study highlights the effect of blood proteins on the viability of the microjets. The presence of blood proteins, including serum albumin and γ‐globulins at physiological concentrations, has been found to dramatically reduce the viability of the microjets. The reduction of viability has been measured in terms of a lower number of active microjets and a decrease in the velocity of propulsion. It is clear from this study that in order for microjets to function in biomedical applications, different modes of propulsion besides platinum‐catalyzed oxygen bubble ejection must be employed. These findings have serious implications for the biomedical applications of catalytic microjets.     

A flow-through microfluidic chip for continuous dielectrophoretic separation of viable and non-viable human T-cells

Effective methods for rapid sorting of cells according to their viability are critical in T cells based therapies to prevent any risk to patients. In this context, we present a novel microfluidic device that continuously separates viable and non-viable T-cells according to their dielectric properties. A dielectrophoresis (DEP) force is generated by an array of castellated microelectrodes embedded into a microfluidic channel with a single inlet and two outlets; cells subjected to positive DEP forces are drawn toward the electrodes array and leave from the top outlet, those subjected to negative DEP forces are repelled away from the electrodes and leave from the bottom outlet. Computational fluid dynamics is used to predict the device separation efficacy, according to the applied alternative current (AC) frequency, at which the cells move from/to a negative/positive DEP region and the ionic strength of the suspension medium. The model is used to support the design of the operational conditions, confirming a separation efficiency, in terms of purity, of 96% under an applied AC frequency of 1.5 × 10⁶ Hz and a flow rate of 20 μl/h. This work represents the first example of effective continuous sorting of viable and non-viable human T-cells in a single-inlet microfluidic chip, paving the way for lab-on-a-chip applications at the point of need.     

基于实时无标记技术研究流式分选后细胞活性的检测方法

利用流式细胞法、细胞计数试剂盒（CCK-8）法、实时细胞功能分析（RTCA）法分别检测分选前后细胞的活性,综合比较了3种方法的检测原理、操作特点等。结果显示,流式细胞法测得的分选后细胞凋亡率为（3.85 ± 0.008）%,分选前细胞凋亡率为（14.09 ± 0.021）%,分选后细胞凋亡率低于分选前,具有统计学差异（P < 0.05）;分选前后的活细胞比例显示,分选后活细胞比例高于分选前,具有显著性统计学差异（P < 0.001）。CCK-8法测得的分选后细胞活性高于分选前,具有显著性统计学差异（P < 0.001）;RTCA法测得的分选后细胞连续增殖活性明显高于分选前,具有极显著性统计学差异（P < 0.000 1）。结果显示,相较于CCK-8法和流式细胞法,RTCA法的细胞用量少、可回收,操作简便,无需标记,检测灵敏度高,可获得实时动态的细胞生长曲线,适合研究分选后细胞长效动态的活性变化,可为基础和临床分选后活细胞的功能研究提供检测手段。     

Designing quantitative structure activity relationships to predict specific toxic endpoints for polybrominated diphenyl ethers in mammalian cells

Polybrominated diphenyl ethers (PBDEs) are known as effective flame retardants and have vast industrial application in products like plastics, building materials and textiles. They are found to be structurally similar to thyroid hormones that are responsible for regulating metabolism in the body. Structural similarity with the hormones poses a threat to human health because, once in the system, PBDEs have the potential to affect thyroid hormone transport and metabolism. This study was aimed at designing quantitative structure–activity relationship (QSAR) models for predicting toxic endpoints, namely cell viability and apoptosis, elicited by PBDEs in mammalian cells. Cell viability was evaluated quantitatively using a general cytotoxicity bioassay using Janus Green dye and apoptosis was evaluated using a caspase assay. This study has thus modelled the overall cytotoxic influence of PBDEs at an early and a late endpoint by the Genetic Function Approximation method. This research was a twofold process including running in vitro bioassays to collect data on the toxic endpoints and modeling the evaluated endpoints using QSARs. Cell viability and apoptosis responses for Hep G2 cells exposed to PBDEs were successfully modelled with an r² of 0.97 and 0.94, respectively.     

Optimization of Biocompatibility for a Hydrophilic Biological Molecule Encapsulation System

Despite considerable advances in recent years, challenges in delivery and storage of biological drugs persist and may delay or prohibit their clinical application. Though nanoparticle-based approaches for small molecule drug encapsulation are mature, encapsulation of proteins remains problematic due to destabilization of the protein. Reverse micelles composed of decylmonoacyl glycerol (10MAG) and lauryldimethylamino-N-oxide (LDAO) in low-viscosity alkanes have been shown to preserve the structure and stability of a wide range of biological macromolecules. Here, we present a first step on developing this system as a future platform for storage and delivery of biological drugs by replacing the non-biocompatible alkane solvent with solvents currently used in small molecule delivery systems. Using a novel screening approach, we performed a comprehensive evaluation of the 10MAG/LDAO system using two preparation methods across seven biocompatible solvents with analysis of toxicity and encapsulation efficiency for each solvent. By using an inexpensive hydrophilic small molecule to test a wide range of conditions, we identify optimal solvent properties for further development. We validate the predictions from this screen with preliminary protein encapsulation tests. The insight provided lays the foundation for further development of this system toward long-term room-temperature storage of biologics or toward water-in-oil-in-water biologic delivery systems.