The Notch signaling pathway in retinal dysplasia and retina vascular homeostasis

The retina is one of the most essential elements of vision pathway in vertebrate. The dysplasia of retina cause congenital blindness or vision disability in individuals, and the misbalance in adult retinal vascular homeostasis leads to neovaseularization-associated diseases in adults, such as diabetic retinopathy or age-related macular degeneration. Many developmental signaling pathways are involved in the process of retinal development and vascular homeostasis. Among them, Notch signaling pathway has long been studied, and Notch signaling-interfered mouse models show both neural retina dysplasia and vascular abnormality. In this review, we discuss the roles of Notch signaling in the maintenance of retinal progenitor cells, specification of retinal neurons and glial cells, and the sustaining of retina vascular homeostasis, especially from the aspects of conditional knockout mouse models. The potential of Notch signal mampulation may provide a powerful cell fate- and neovascularization-controlling tool that could have important applications in la'eatment of retinal diseases.     

microRNA-21-5p from M2 macrophage-derived extracellular vesicles promotes the differentiation and activity of pancreatic cancer stem cells by mediating KLF3

Cell Biology and Toxicology - Given the fact that tumor-associated macrophage-derived extracellular vesicles (EVs) are attributable to tumor aggressiveness, this research intends to decode the...     

Mechanical Property Evolution of Silicon Composite Electrodes Studied by Environmental Nanoindentation

Mechanical degradation is largely responsible for the short cycle life of silicon (Si)‐based electrodes for future lithium‐ion batteries. An improved fundamental understanding of the mechanical behavior of Si electrodes, which evolves, as demonstrated in this paper, with the state of charge (SOC) and the cycle number, is a prerequisite for overcoming mechanical degradation and designing high capacity and durable Si‐based electrodes. In this study, Young's modulus (E) and hardness (H) of Si composite electrodes at different SOCs and after different cycle numbers are measured by nanoindentation under both dry and wet (liquid electrolyte) conditions. Unlike electrodes made of Si alone, E and H values of Si composite electrodes increase with increasing Li concentration. The composite electrodes under wet conditions are softer than that under dry conditions. Both E and H decrease with the cycle number. These findings highlight the effects of porosity, liquid environment, and degradation on the mechanical behavior of composite electrodes. The methods and results of this study on the mechanical property evolution of Si/polyvinylidene fluoride electrodes form a basis for exploring more effective binders for Si‐based electrodes. Furthermore, the evolving nature of the mechanical behavior of composite electrodes should be taken into consideration in future modeling efforts of porous composite electrodes.     

Asymmetric Rate Behavior of Si Anodes for Lithium‐Ion Batteries: Ultrafast De‐Lithiation versus Sluggish Lithiation at High Current Densities

The combined effect of lithium‐ion diffusion, potential‐concentration gradient, and stress plays a critical role in the rate capability and cycle life of Si‐based anodes of lithium‐ion batteries. In this work, Si nanofilm anodes are shown to exhibit an asymmetric rate performance: around 72% of the total available capacity can be delivered during de‐lithiation under a high current density of 420 A g^‐1 (100C where C is the charge‐rate) in 22 s; in striking contrast, only 1% capacity can be delivered during lithiation. A mathematical model of single‐ion diffusion is established to elucidate the asymmetric rate performance, which can be mainly attributed to the potential‐concentration profile associated with the active material and the ohmic voltage shift under high currents; the difference in chemical diffusion coefficients during lithiation and de‐lithiation also plays a role. This clarifies that the charge and discharge rates of lithium‐ion‐battery electrodes should be evaluated separately due to the asymmetric effect in the electrochemical system.     

贡嘎山国家级自然保护区兔狲的活动节律与适宜栖息地预测

2016年6月-2017年5月,采用红外相机陷阱法研究了四川贡嘎山国家级自然保护区兔狲Otocolobus manul的活动节律,以样线法和红外相机调查得到的兔狲分布点为数据源,采用最大熵(MaxEnt)模型预测了兔狲的适宜栖息地分布。结果显示:(1)兔狲分布在海拔3 780~4 956 m的灌丛、草甸和流石滩生境,其中87.2%的分布点位于海拔4 500 m以上;(2)日活动差异指数为0.071 2,昼行性指数为0.34,兔狲的活动高峰为05∶00-07∶00和20∶00-22∶00;(3)增强型植被指数2年最大值均值、海拔、平均日较差和气温年较差是影响兔狲栖息地选择的主要环境因子,兔狲偏好在海拔4 000 m以上、温差较大的高山流石滩生境活动,保护区兔狲的适宜栖息地面积为187 km^2,占保护区总面积的4.56%。本研究充实了兔狲的生物学、生态学资料,也为该物种的保护管理提供了参考资料。     

Expression,purification and characterization of the extracellular domain of human Flt3 ligand in <Emphasis Type="Italic">Escherichia coli</Emphasis>

Fms-like tyrosine kinase 3 ligand (Flt3 ligand, FL) is a cytokine that affects the growth, survival and/or differentiation of hematopoietic cells through the activation of specific tyrosine kinase receptors, and is potentially useful for in vitro HSC amplification. To express the extracellular domain of human Flt3 ligand (hFL^ext) in Escherichia coli, we cloned hFL^ext and constructed the recombinant expression vector pET32a-hFL^ext. hFL^ext was successfully expressed in E. coli as a Trx fusion protein (Trx-hFL^ext) under IPTG (isopropyl-β-d-thiogalactopyranoside) induction for 12 h at 30°C. The Trx-hFL^ext protein, expressed in inclusion bodies even at a low induction temperature, was successfully refolded and purified using dialysis and affinity chromatography. The purified hFL^ext was biologically active and could effectively stimulate the proliferation of mouse bone marrow nucleated cells revealed by cell proliferation assay and colony forming assay. In addition, in synergize with G-CSF and TPO, recombinant purified hFL^ext could stimulate ex vivo expansion of murine Lin⁻Sca-1⁺c-Kit⁺ cells. Therefore, using the E. coli expression system and an affinity chromatography system, we successfully expressed, refolded, and purified a biologically active Trx-hFL^ext protein which might be potentially useful for in vitro HSC amplification.     

The Hippo Pathway Effector YAP Regulates Motility,Invasion, and Castration-Resistant Growth of Prostate Cancer Cells

Yes-associated protein (YAP) is an effector of the Hippo tumor suppressor pathway. The functional significance of YAP in prostate cancer has remained elusive. In this study, we first show that enhanced expression of YAP is able to transform immortalized prostate epithelial cells and promote migration and invasion in both immortalized and cancerous prostate cells. We found that YAP mRNA was upregulated in androgen-insensitive prostate cancer cells (LNCaP-C81 and LNCaP-C4-2 cells) compared to the level in androgen-sensitive LNCaP cells. Importantly, ectopic expression of YAP activated androgen receptor signaling and was sufficient to promote LNCaP cells from an androgen-sensitive state to an androgen-insensitive state in vitro, and YAP conferred castration resistance in vivo. Accordingly, YAP knockdown greatly reduced the rates of migration and invasion of LNCaP-C4-2 cells and under androgen deprivation conditions largely blocked cell division in LNCaP-C4-2 cells. Mechanistically, we found that extracellular signal-regulated kinase–ribosomal s6 kinase signaling was downstream of YAP for cell survival, migration, and invasion in androgen-insensitive cells. Finally, immunohistochemistry showed significant upregulation and hyperactivation of YAP in castration-resistant prostate tumors compared to their levels in hormone-responsive prostate tumors. Together, our results identify YAP to be a novel regulator in prostate cancer cell motility, invasion, and castration-resistant growth and as a potential therapeutic target for metastatic castration-resistant prostate cancer (CRPC).