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.     

Metformin Preserves β-Cell Compensation in Insulin Secretion and Mass Expansion in Prediabetic Nile Rats

Prediabetes is a high-risk condition for type 2 diabetes (T2D). Pancreatic β-cells adapt to impaired glucose regulation in prediabetes by increasing insulin secretion and β-cell mass expansion. In people with prediabetes, metformin has been shown to prevent prediabetes conversion to diabetes. However, emerging evidence indicates that metformin has negative effects on β-cell function and survival. Our previous study established the Nile rat (NR) as a model for prediabetes, recapitulating characteristics of human β-cell compensation in function and mass expansion. In this study, we investigated the action of metformin on β-cells in vivo and in vitro. A 7-week metformin treatment improved glucose tolerance by reducing hepatic glucose output and enhancing insulin secretion. Although high-dose metformin inhibited β-cell glucose-stimulated insulin secretion in vitro, stimulation of β-cell insulin secretion was preserved in metformin-treated NRs via an indirect mechanism. Moreover, β-cells in NRs receiving metformin exhibited increased endoplasmic reticulum (ER) chaperones and alleviated apoptotic unfold protein response (UPR) without changes in the expression of cell identity genes. Additionally, metformin did not suppress β-cell mass compensation or proliferation. Taken together, despite the conflicting role indicated by in vitro studies, administration of metformin does not exert a negative effect on β-cell function or cell mass and, instead, early metformin treatment may help protect β-cells from exhaustion and decompensation.     

感官代偿在药品盲用无障碍包装设计中的应用研究

目的 针对盲人难以精准、便捷、安全服药的问题，基于感官代偿原理，研究如何利用触觉、听觉等感官代偿的潜在优势设计“适盲性”药品无障碍包装，辅助盲人实现科学、合理、精准用药。方法 基于盲人的生理和心理特点，分析药品包装在适应盲人使用时的“痛点”，在把握盲人感官代偿机理的基础上，结合具体案例，研究药品包装适盲性无障碍设计的途径和方法。结论 在基于盲人特殊的感官代偿机制设计盲用无障碍药品包装时，要理性、深度地思考如何最大限度地激发触觉和听觉的代偿潜能来解决盲人的服药障碍问题。通过简洁规范的盲文标注设计、科学合理的适盲性结构设计、智能交互的语音指令设计等方式，改善药品包装的核心信息呈现方式，提升药品信息传递的便捷性和准确性，使盲人能够独立自主地识药、取药和服药。     

Photophysical investigation of the formation of defect levels in P doped ZnO thin films

Zinc oxide (ZnO) offers a major disadvantage of asymmetry doping in terms of reliability, stability, and reproducibility of p-type doping, which is the main hindrance in realization of optoelectronic devices. The problem is even more complicated due to formation of various native defects in unintentionally doped n-type ZnO. The realization of p-type conductivity in doped ZnO requires an in-depth understanding of the formation of an effective shallow acceptor, as well as donor-acceptor compensation. Photophysical properties such as photoconductivity along with photoluminescence (PL) studies have unprecedentedly and effectively been utilized in this work to monitor the evolution of various in-gap defects. Phosphorus (P) doped ZnO thin films have been grown by RF magnetron sputtering under various Ar to O₂ gas ratios to investigate the effect of O₂ on the donor-acceptor compensation by comprehensive photoconductivity measurements supported by the PL studies. Initial elemental analyses indicate presence of abundant zinc vacancies (V_Zn) in O-rich ambience. The results predict that P sits in the zinc (Zn) site rather than the oxygen (O) site causing the formation of P_Zn–2V_Zn acceptor-like defects, which compensates the donor defects in P doped ZnO films. Photocurrent spectra uniquely reveal presence of more oxygen vacancies (V_O) defects states in lower O₂ flow, which gets compensated with an increase in the O₂ flow. Successive photocurrent transients indicate probable presence of more V_O in the films grown with lower O₂ flow and more V_Zn in higher O₂ flow. Overall the photosensitivity measurements clearly present that O-rich ambience expedites the formation of acceptor defects which are compensated, thereby lowering the dark current and enhancing the ultraviolet photosensitivity.     

Analysis and proposition of limiting current density measurement protocol

Limiting current density at different temperatures, backpressures, and balance gases can be used to separate molecular diffusion resistance, Knudsen diffusion resistance and local transport resistance of membrane electrode assembly (MEA). However, the measurement of limiting current density has no unified protocol. The diverse choices in the literature, either in the control of current or voltage or in the atmosphere like relative humidity and O₂ concentrations, make it difficult to compare the results and identify the true bottleneck hindering the mass transport. In this work, the current-voltage curves obtained by current scanning/stepping and voltage scanning/stepping methods under dilute O₂ of different concentrations and a wide range of relative humidity were measured and analyzed systematically. It is found that the voltage stepping method is superior to the other three ways of control for the reliable determination of the limiting current density. Aided with simultaneous electrochemical impedance spectroscopy measurement, the limiting current density can be determined with pinpoint accuracy. When the limiting current density is just used to qualitatively evaluate different MEA, the voltage scanning method can be used instead for its high time efficiency. The selection of the atmosphere also plays an important role in suppressing the distortion from excessive water and reducing the spurious contribution from proton conduction resistance. It is found that O₂ concentrations at 0.5 vol% and relative humidity at 90% can give the best estimation of O₂ transport resistance in membrane electrode assembly.     

Electrochemical Quantification of Neurotransmitters in Single Live Cell Vesicles Shows Exocytosis is Predominantly Partial

Exocytosis plays an essential role in the communication between cells in the nervous system. Understanding the regulation of neurotransmitter release during exocytosis and the amount of neurotransmitter content that is stored in vesicles is of importance, as it provides fundamental insights to understand how the brain works and how neurons elicit a certain behavior. In this minireview, we summarize recent progress in amperometric measurements for monitoring exocytosis in single cells and electrochemical cytometry measurements of vesicular neurotransmitter content in individual vesicles. Important steps have increased our understanding of the different mechanisms of exocytosis. Increasing evidence is firmly establishing that partial release is the primary mechanism of release in multiple cell types.     

Steering feel improvement by mathematical modeling of the Electric Power Steering system

Currently, the Electric Power Steering (EPS) system is an essential component of the vehicle because it provides assistive steering torque to the driver. To ensure a faster steering response, the position of the EPS in some vehicles is moved closer to the tire rather than the steering wheel. The steering torque, which is provided by the EPS in the steering system, mainly affects the driver’s feel while steering. Therefore, the driver often feels uncomfortable owing to such positioning of the EPS in the steering system. In particular, the nonlinearity of the Universal Joint (UJ), which is one of parts of the steering system, can be felt at the steering wheel side.In this paper, we proposed an algorithm based on the mathematical model of the steering torque in the steering system to improve the steering feel. The mathematical model is structured using parameters that can be obtained from the information of the steering system. Moreover, the formulation of the steering torque consists of the two parts, namely the deformation part, which describes the propagation inside the steering system, and the friction part that describes the inherent friction in the UJ.Simulation and experiments were conducted to verify the proposed mathematical model with similar conditions to the real tire load during the steering motion. Furthermore, to improve the driver’s feel during steering, a torque compensation algorithm is proposed and verified through experiments.     

Microcrack healing in zirconia ceramics under a DC electric field/current

Flash event caused by a DC electric field/current was applied to the crack healing in 8 mol % Y₂O₃ stabilized cubic ZrO₂ polycrystals (8Y-CSZ). The flash event, which occurred by applying the DC power higher than a critical value of 100 mW/mm³, successfully healed the microcrack within several minutes without any healing agents at a furnace temperature of 800 °C. As compared to the healing treatment under static annealing, the healing phenomena were accelerated about 2 times under the flash treatment even at the same temperatures, suggesting that the enhanced healing phenomena cannot be explained only by the temperature effect. Since the rate of grain growth was accelerated under the flash treatment, the flash healing would be accelerated through the current-enhanced diffusional processes. This study shows for the first time that the flash event has a potential to apply to the crack healing process in the ceramic materials and composites.