Identification and Optimization of 4‐Anilinoquinolines as Inhibitors of Cyclin G Associated Kinase

4‐Anilinoquinolines were identified as potent and narrow‐spectrum inhibitors of the cyclin G associated kinase (GAK), an important regulator of viral and bacterial entry into host cells. Optimization of the 4‐anilino group and the 6,7‐quinoline substituents produced GAK inhibitors with nanomolar activity, over 50 000‐fold selectivity relative to other members of the numb‐associated kinase (NAK) subfamily, and a compound (6,7‐dimethoxy‐N‐(3,4,5‐trimethoxyphenyl)quinolin‐4‐amine; 49 ) with a narrow‐spectrum kinome profile. These compounds may be useful tools to explore the therapeutic potential of GAK in prevention of a broad range of infectious and systemic diseases.     

NMR microscopy of single neurons at 500 MHZ

Previous NMR microimaging studies at 360 MHz have demonstrated a clear differentiation between the nucleus and cytoplasm in isolated single neurons. In particular, theT ₂ of the cell nucleus is 2.5 times larger than that of the cytoplasm. In order to determine the magnitude of possibleT ₂ ^* influences on these observations, images of single cells have been obtained at 500 MHz using spin-echo and line-narrowing sequences. Comparison of the images acquired by the two sequences, and of the spin-echo images at 360 and 500 MHz, imply that anyT ₂ ^* contributions are relatively small. Consequently, the measuredT ₂ differences in spin-echo imaging represent a true difference in theT ₂ relaxation in the two cellular compartments.     

Visible emission and energy transfer in Tb3+/Dy3+ co-doped phosphate glasses

In this work, we systematically study the spectroscopic properties of Tb³⁺/Dy³⁺ co-doped phosphate glasses in the visible spectral region and explore the sensitization role of Dy³⁺ in the enhancement of visible fluorescence of Tb³⁺ ions. Judd-Ofelt parameters Ω₂ and Ω₄/Ω₆ of the phosphate glass as host for Tb³⁺ are calculated as 21.60 × 10^-20 cm² and 0.73, respectively, based on the measured spectral absorption. Multiple energy transfer (ET) routes from Dy³⁺ to Tb³⁺ and their efficiencies are characterized, and the enhanced fluorescence properties of Tb³⁺ are investigated, including the emission spectral strength and the spontaneous emission lifetime as functions of Dy³⁺ doping concentration. The efficient nonradiative ET processes between Dy³⁺ and Tb³⁺ allow a moderate concentration level of Tb³⁺ to achieve favorably stronger spectral absorption at blue and ultraviolet wavelengths. Tb³⁺/Dy³⁺ co-doped phosphate glass shows promising potential for phosphors and lasing operation at visible wavelengths.     

3D打印混凝土技术在澳大利亚的最近研究进展

3D打印,又被称为增材制造,是通过逐层累积叠加制造三维物体的一种技术手段。过去几年中,这种技术吸引了越来越多来自建筑业的关注。与传统混凝土浇筑技术相比,3D打印混凝土的应用可以实现更加高效的自由建筑制造,同时减小对人工劳动力的依赖。在全球范围内,由于相关高校和科研单位的积极参与,关于3D打印混凝土的研究工作取得了巨大的进展,其中包括澳大利亚的相关研究。本文主要对澳大利亚在3D打印混凝土研究方面有代表性的两所高校的最新进展进行介绍,两所学校分别是皇家墨尔本理工大学(RMIT大学)和斯威本科技大学。本文首先介绍了两所高校的打印设备及其特点,随后讨论了具体研究领域和近期发表的相关文章。RMIT大学主要侧重于研究纤维增强对3D打印混凝土力学性能方面的影响,而斯威本科技大学则着重研究3D打印地聚物混凝土的性能。本文旨在促进相关领域研究人员对澳大利亚3D打印混凝土研究团队和研究进展的理解。     

Discovery of Quinoline‐Derived Trifluoromethyl Alcohols,Determination of Their in vivo Toxicity and Anticancer Activity in a Zebrafish Embryo Model

In this study the rational design, synthesis, and anticancer activity of quinoline‐derived trifluoromethyl alcohols were evaluated. Members of this novel class of trifluoromethyl alcohols were identified as potent growth inhibitors in a zebrafish embryo model. Synthesis of these compounds was carried out with an sp³‐C?H functionalization strategy of methyl quinolines with trifluoromethyl ketones. A zebrafish embryo model was also used to explore the toxicity of ethyl 4,4,4‐trifluoro‐3‐hydroxy‐3‐(quinolin‐2‐ylmethyl)butanoate ( 1 ), 2‐benzyl‐1,1,1‐trifluoro‐3‐(quinolin‐2‐yl)propan‐2‐ol ( 2 ), and trifluoro‐3‐(isoquinolin‐1‐yl)‐2‐(thiophen‐2‐yl)propan‐2‐ol ( 3 ). Compounds 2 and 3 were found to be more toxic than compound 1 ; apoptotic staining assays indicated that compound 3 causes increased cell death. In vitro cell proliferation assays showed that compound 2 , with an LC₅₀ value of 14.14 μm , has more potent anticancer activity than cisplatin. This novel class of inhibitors provides a new direction in the discovery of effective anticancer agents.     

Human Adipose Tissue Conditioned Media from Lean Subjects Is Protective against H2O2 Induced Neurotoxicity in Human SH-SY5Y Neuronal Cells

Adipose tissue secretes numerous hormone-like factors, which are known as adipokines. Adipokine receptors have been identified in the central nervous system but the potential role of adipokine signaling in neuroprotection is unclear. The aim of this study is to determine (1) Whether adipokines secreted from cultured adipose tissue of lean humans is protective against oxidative stress-induced neurotoxicity in human SH-SY5Y neuronal cells; and (2) To explore potential signaling pathways involved in these processes. Adipose tissue conditioned media (ATCM) from healthy lean subjects completely prevented H₂O₂ induced neurotoxicity, while this effect is lost after heating ATCM. ATCM activated the phosphorylation of ERK1/2, JNK and Akt at serine 308 in SH-SY5Y cells. PD98059 (25 µM), SP600125 (5 µM) and LY29400 (20 µM) partially blocked the protective effects of ATCM against H₂O₂ induced neurotoxicity. Findings demonstrate that heat-sensitive factors secreted from human adipose tissue of lean subjects are protective against H₂O₂ induced neurotoxicity and ERK1/2, JNK, and PI3K signaling pathways are involved in these processes. In conclusion, this study demonstrates preliminary but encouraging data to further support that adipose tissue secreted factors from lean human subjects might possess neuroprotective properties and unravel the specific roles of ERK1/2, JNK and PI3K in these processes.