Portrait of Cancer Stem Cells on Colorectal Cancer: Molecular Biomarkers,Signaling Pathways and miRNAome

Colorectal cancer (CRC) is a leading cause of cancer death worldwide, and about 20% is metastatic at diagnosis and untreatable. Increasing evidence suggests that the heterogeneous nature of CRC is related to colorectal cancer stem cells (CCSCs), a small cells population with stemness behaviors and responsible for tumor progression, recurrence, and therapy resistance. Growing knowledge of stem cells (SCs) biology has rapidly improved uncovering the molecular mechanisms and possible crosstalk/feedback loops between signaling pathways that directly influence intestinal homeostasis and tumorigenesis. The generation of CCSCs is probably connected to genetic changes in members of signaling pathways, which control self-renewal and pluripotency in SCs and then establish function and phenotype of CCSCs. Particularly, various deregulated CCSC-related miRNAs have been reported to modulate stemness features, controlling CCSCs functions such as regulation of cell cycle genes expression, epithelial-mesenchymal transition, metastasization, and drug-resistance mechanisms. Primarily, CCSC-related miRNAs work by regulating mainly signal pathways known to be involved in CCSCs biology. This review intends to summarize the epigenetic findings linked to miRNAome in the maintenance and regulation of CCSCs, including their relationships with different signaling pathways, which should help to identify specific diagnostic, prognostic, and predictive biomarkers for CRC, but also develop innovative CCSCs-targeted therapies.     

A Bio-Conjugated Fullerene as a Subcellular-Targeted and Multifaceted Phototheranostic Agent

Fullerenes are candidates for theranostic applications because of their high photodynamic activity and intrinsic multimodal imaging contrast. However, fullerenes suffer from low solubility in aqueous media, poor biocompatibility, cell toxicity, and a tendency to aggregate. C₇₀@lysozyme is introduced herein as a novel bioconjugate that is harmless to a cellular environment, yet is also photoactive and has excellent optical and optoacoustic contrast for tracking cellular uptake and intracellular localization. The formation, water-solubility, photoactivity, and unperturbed structure of C₇₀@lysozyme are confirmed using UV-visible and 2D ¹H, ¹⁵N NMR spectroscopy. The excellent imaging contrast of C₇₀@lysozyme in optoacoustic and third harmonic generation microscopy is exploited to monitor its uptake in HeLa cells and lysosomal trafficking. Last, the photoactivity of C₇₀@lysozyme and its ability to initiate cell death by means of singlet oxygen (¹O₂) production upon exposure to low levels of white light irradiation is demonstrated. This study introduces C₇₀@lysozyme and other fullerene-protein conjugates as potential candidates for theranostic applications.     

冰下单载波水声通信试验研究

北极地区战略地位的提高促进了极区各种应用的快速发展，冰下水声通信成为其中一个热点问题。为了研究冰下单载波水声通信性能，在黄海冰区开展冰下试验。重点分析了内嵌锁相环的多通道判决反馈均衡(Multi-channelDecision Feedback Equalization, M-DFE)技术在冰下水声通信中抗多途时延的能力，研究比较了改进比例归一化最小均方(Improved Proportional normalized Least Mean Square, IPNLMS)算法和递归最小二乘(Recursive Least Squares,RLS)算法的均衡性能。试验结果表明IPNLMS和RLS都能克服信道多途效应带来的影响。在牺牲计算复杂度的前提下，RLS具有更好的均衡效果，M-DFE在冰下环境中能够有效消除码间干扰。     

Pleiotropic Effects of Sodium-Glucose Cotransporter-2 Inhibitors: Renoprotective Mechanisms beyond Glycemic Control

Diabetes mellitus is a major cause of chronic kidney disease and end-stage renal disease. However, the management of chronic kidney disease, particularly diabetes, requires vast improvements. Recently, sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally developed for the treatment of diabetes, have been shown to protect against kidney injury via glycemic control, as well as various other mechanisms, including blood pressure and hemodynamic regulation, protection from lipotoxicity, and uric acid control. As such, regulation of these mechanisms is recommended as an effective multidisciplinary approach for the treatment of diabetic patients with kidney disease. Thus, SGLT2 inhibitors are expected to become key drugs for treating diabetic kidney disease. This review summarizes the recent clinical evidence pertaining to SGLT2 inhibitors as well as the mechanisms underlying their renoprotective effects. Hence, the information contained herein will advance the current understanding regarding the pleiotropic effects of SGLT2 inhibitors, while promoting future research in the field.     

基于平均功率平衡控制的磁悬浮分子泵电力失效补偿方法

高速磁悬浮涡轮分子泵（Turbo Molecular Pump, TMP）因其高能量密度、微振动、无需润滑等优点被广泛应用于工业领域，但外部电源失效时，高速转子跌落后与保护轴承产生剧烈撞击和摩擦，将给系统带来致命损害。针对以上问题，提出一种基于平均功率平衡法的电力失效补偿控制（Power Failure Compensation Control, PFCC）方法。首先，设计电机能量回馈电路；其次，对Buck-Boost变换器进行数学建模，设计一种双环非线性控制器，其中电流内环使用滑模控制，电压外环使用平均功率平衡控制（Average Power Balance Control, APBC），并利用Lyapunov函数推导出系统的稳定性条件；最后，通过搭建磁悬浮分子泵PFCC实验平台，对所提出的方法进行实验验证。结果表明：本文所提出的方法具有快速响应和输出鲁棒性，磁悬浮转子由额定转速21000 r/min降至3900 r/min时跌落，电机能量转化效率为96.6%，提高了磁轴承系统的安全性。     

高压气动系统负载容腔压力伺服控制仿真研究

为满足某气体发生系统安装空间小、重量轻、动态响应快、控制精度高等要求，设计了高压气动压力伺服控制系统，并采用高压电-气伺服阀实现了负载压力的高响应高精度控制。建立了系统数学模型，包括高压气瓶热力学方程、高压电-气伺服阀传递函数与流量方程、负载容腔压力变化与排气流量方程等子模型，并设计了反馈线性化PID控制器。基于MATLAB/Simulink平台建立了高压气动系统仿真模型，仿真研究了高压气瓶容积与初始气源压力、负载容腔排气孔通径等参数对系统负载压力控制性能的影响规律。研究结果为该系统的优化设计与实验研究提供重要理论依据。     

A high-throughput chaotic advection microreactor for preparation of uniform and aggregated barium sulfate nanoparticles

A high-throughput (105.5 g/h) passive four-stage asymmetric oscillating feedback microreactor using chaotic mixing mechanism was developed to prepare aggregated Barium sulfate (BaSO₄) particles of high primary nanoparticle size uniformity. Three-dimensional unsteady simulations showed that chaotic mixing could be induced by three unique secondary flows (i.e., vortex, recirculation, and oscillation), and the fluid oscillation mechanism was examined in detail. Simulations and Villermaux–Dushman experiments indicate that almost complete mixing down to molecular level can be achieved and the prepared BaSO₄ nanoparticles were with narrow primary particle size distribution (PSD) having geometric standard deviation, σ_g, less than 1.43 when the total volumetric flow rate Q_total was larger than 10 ml/min. By selecting Q_total and reactant concentrations, average primary particle size can be controlled from 23 to 109 nm as determined by microscopy. An average size of 26 nm with narrow primary PSD (σ_g = 1.22) could be achieved at Q_total of 160 ml/min.     

面向二进制程序的导向性模糊测试方法

为了解决当前模糊测试技术中变异存在一定的盲目性以及变异生成的样本大多经过相同的高频路径的问题，提出并实现了一种基于轻量级程序分析技术的二进制程序模糊测试方法。首先对目标二进制程序进行静态分析来筛选在模糊测试过程中阻碍样本文件深入程序内部的比较指令；随后对目标文件进行插桩来获取比较指令中操作数的具体值，并根据该具体值为比较指令建立实时的比较进度信息，通过比较进度衡量样本的重要程度；然后基于模糊测试过程中实时的路径覆盖信息为经过稀有路径的样本增加其被挑选进行变异的概率；最后根据比较进度信息并结合启发式策略有针对性地对样本文件进行变异，通过变异引导提高模糊测试中生成能够绕过程序规约检查的有效样本的效率。实验结果表明，所提方法发现crash及发现新路径的能力均优于模糊测试工具AFL-Dyninst。     

Boccia game simulator: Serious game adapted for people with disabilities

Integration in the world of sport is one way for individuals with disabilities or motor disorders to feel more socially integrated, independent, and confident. Boccia is a Paralympic sport, which is increasingly getting more attention around the world. These facts have contributed to the objectives of this work. Including it in the serious games category enables to develop and rehabilitate the cognitive capabilities. The main focus was BC3 classification athletes (users with limited motor characteristics that require the use of an assistive device—a ramp, in this case). This paper describes a realistic Boccia game simulator adapted for people with disabilities that integrates a set of features that includes real physics and social features. These features can be used to enhance the interest of nonpractitioners of the sport and to improve the training conditions. The official Boccia regulation was added to the design of the simulator. The usability and approximation to the reality of the simulator were tested and validated based on the tests performed and data collected via a survey of users with no motor or psychological disorders. Realism and usability rating was almost excellent, and good results were achieved at the assessment of the game experience.     

A Versatile Theranostic Nanoemulsion for Architecture‐Dependent Multimodal Imaging and Dually Augmented Photodynamic Therapy

To design a clinically translatable nanomedicine for photodynamic theranostics, the ingredients should be carefully considered. A high content of nanocarriers may cause extra toxicity in metabolism, and multiple theranostic agents would complicate the preparation process. These issues would be of less concern if the nanocarrier itself has most of the theranostic functions. In this work, a poly(ethylene glycol)‐boron dipyrromethene amphiphile (PEG‐F₅₄‐BODIPY) with 54 fluorine‐19 (¹⁹F) is synthesized and employed to emulsify perfluorohexane (PFH) into a theranostic nanoemulsion (PFH@PEG‐F₅₄‐BODIPY). The as‐prepared PFH@PEG‐F₅₄‐BODIPY can perform architecture‐dependent fluorescence/photoacoustic/¹⁹F magnetic resonance multimodal imaging, providing more information about the in vivo structure evolution of nanomedicine. Importantly, this nanoemulsion significantly enhances the therapeutic effect of BODIPY through both the high oxygen dissolving capability and less self‐quenching of BODIPY molecules. More interestingly, PFH@PEG‐F₅₄‐BODIPY shows high level of tumor accumulation and long tumor retention time, allowing a repeated light irradiation after a single‐dose intravenous injection. The “all‐in‐one” photodynamic theranostic nanoemulsion has simple composition, remarkable theranostic efficacy, and novel treatment pattern, and thus presents an intriguing avenue to developing clinically translatable theranostic agents.