Search

2D cell cultures are suitable for rapid exploration of the factors in the extracellular matrix affecting the development of cells. The technology of the micrometre-sized hydrogel array provides a feasible, miniaturized, and high-throughput strategy for the process. However, current microarray devices lack a handy and parallelized methodology in sample treatment, which makes the process of high-throughput cell screening (HTCS) expensive and inefficient. Here, based on the functionalization of micro-nano structures and the fluid control capability of microfluidic chips, we build a microfluidic spotting-screening platform (MSSP). The MSSP can print 20000 microdroplet spots within 5 min, coupled with a simple strategy for parallel addition of compound libraries. Compared with open microdroplet arrays, the MSSP can control the evaporation rate of nanoliter droplets, providing a stable fabrication platform for hydrogel-microarray-based materials. As a proof-of-concept demonstration, the MSSP successfully controlled the adhesion, adipogenic, and osteogenic differentiation behavior of mesenchymal stem cells by rationally designing the substrate stiffness, adhesion area, and cell density. We anticipate that the MSSP may provide an accessible and promising tool for hydrogel-based HTCS. High-throughput screening of cells is a common approach to improve the efficiency of biological experiments, and one challenge of the existing technologies is to achieve rapid and precise cell screening with a low-cost and simple strategy. Through the integration of the microfluidic and micro-nanostructure technologies, we fabricated a microfluidic spotting-screening platforms. Benefiting from the flexible control of the fluids, the device can print 20000 microdroplet spots within 5 min, coupled with a simple procedure for parallel addition of compound libraries. High-throughput screening of stem cell lineage specification has also been achieved by the platform, which provides a high-throughput, high-content information extraction strategy for cell-biomaterial interaction research. [Display omitted] [ABSTRACT FROM AUTHOR]

Transcriptional silencing of the FMR1 gene in fragile X syndrome (FXS) leads to the loss of the RNA-binding protein FMRP. In addition to regulating mRNA translation and protein synthesis, emerging evidence suggests that FMRP acts to coordinate proliferation and differentiation during early neural development. However, whether loss of FMRP-mediated translational control is related to impaired cell fate specification in the developing human brain remains unknown. Here, we use human patient induced pluripotent stem cell (iPSC)-derived neural progenitor cells and organoids to model neurogenesis in FXS. We developed a high-throughput, in vitro assay that allows for the simultaneous quantification of protein synthesis and proliferation within defined neural subpopulations. We demonstrate that abnormal protein synthesis in FXS is coupled to altered cellular decisions to favor proliferative over neurogenic cell fates during early development. Furthermore, pharmacologic inhibition of elevated phosphoinositide 3-kinase (PI3K) signaling corrects both excess protein synthesis and cell proliferation in a subset of patient neural cells. [Display omitted] • Global protein synthesis and PI3K signaling are elevated in FXS patient NPCs • neurOMIP provides cell-type-specific readouts of translation and proliferation • Translational defect in FXS is more profound during early neurogenesis • PI3K inhibition selectively corrects cell fate and protein synthesis defects Raj et al. developed a multiparametric assay to measure cellular and molecular phenotypes during neurogenesis in fragile X syndrome iPSC-derived neural cells. Relative to controls, FXS patient cultures have more proliferative cells with increased protein synthesis. Defects in cell fate acquisition can be normalized by inhibiting overactive PI3K signaling. [ABSTRACT FROM AUTHOR]

Abstract: The synthesis and structure–activity relationships of zygosporamide, a known potent and selective cytotoxic natural product against SF-268 and RXF 393 cell lines, are described. The potencies of the synthetic zygosporamide are similar to those reported for the natural product toward all cancer cell lines examined with the exception of SF-268, the underlying cause of which remains to be elucidated. [Copyright &y& Elsevier]

[Display omitted] • Explore the surface configuration in the reaction environment. • State effect of doped iron atom on surface configuration and activity. • Discuss the influence of Ni vacancy. β -NiOOH shows excellent oxygen evolution reaction (OER) catalytic activity under alkaline conditions, but the surface structure under the working environment is not yet fully established. Through ab initio thermodynamic approach, the relationship between catalyst surface structure and pH, electrode potential was studied. For the most stable state of the catalyst surfaces, three adsorbing oxygen atoms and one Ni vacancy form. Doped iron decreases the formation energy of Ni vacancy thus increasing the stable range of surface states. OER mechanism was explored based on the obtained most stable structures. The first step of the reaction is the desorption of oxygen rather than the formation of *OH due to large Steric effects. Ni vacancy reduces the dehydrogenation energy of the adsorbate *OOH and the formation energy of oxygen radical. The interaction between iron and oxygen atom is large than the Ni and oxygen. Therefore, Fe-doped system reduces the formation energy of *O and changes the potential-limited step from the formation of adsorbate *O to the desorption of O 2. [ABSTRACT FROM AUTHOR]

Lignocellulose (LNC) multi-walled carbon nanotubes (MWCNTs) composites were synthesized by covalently grafting a natural polymer, lignocellulose, onto MWCNTs in an ionic liquid, 1-allyl-3-methylimidazolium chloride (AmimCl). Furthermore, the grafting of LNC facilitated the dispersion of the MWCNTs in AmimCl and MWCNTs/LNC films. The elongation at break and tensile strength of grafted-MWCNTs/LNC films with 3 wt% of MWCNTs content were 12.2% and 106.7 MPa respectively, which was almost 93.7% and 10.7% higher than those of the pristine MWCNTs/LNC films. This finding clearly revealed that the mechanical properties of grafted-MWCNTs/LNC films were dramatically superior to those of the MWCNTs/LNC films. [ABSTRACT FROM AUTHOR]

• A novel class of continuum robots named chain telescopic robot is proposed. • The design methodology of this robot is proposed systematically. • Comparative analysis of telescopic arm using two dynamic models has been achieved. • The mass-spring-damping model is more suitable for this kind of telescopic arm. The demands of continuum robots, which can achieve remote operations or pushing objects, are immense in armoured vehicles, submarines and space stations. A novel class of continuum robots named chain telescopic robots (CT-Robots), which consist of many rigid links, can be stored in a constrained space or form a telescopic arm with higher stiffness and arbitrary length. The design methodology of a CT-Robot is systematically presented concerning link connection, drive unit and chain box. However, current studies on CT-Robots lacks evidence on the comparative performance of different dynamic models for the vibration responses of telescopic arms. The mass-spring-damping model (MSD-model) of the telescopic arm is derived and compared with the cantilever beam model (CB-model). We test the models on the CT-Robot with friction wheels by extending the telescopic arm under two conditions. Our results suggest that the MSD-model more accurately describes the real dynamic responses (lateral displacement, velocity, acceleration) of the telescopic arm. In particular, the Euclidean distance d y ,m between the results of the MSD-model and vibration experiments declines by 57.93% and 41.54% compared with that of the CB-model. [ABSTRACT FROM AUTHOR]

Abstract: Cellular protein synthesis is initiated with methionine in eukaryotes with few exceptions. Methionine aminopeptidases (MetAPs) which catalyze the process of N-terminal methionine excision are essential for all organisms. In mammals, type 2 MetAP (MetAP2) is known to be important for angiogenesis, while type 1 MetAP (MetAP1) has been shown to play a pivotal role in cell proliferation. Our previous high-throughput screening of a commercial compound library uncovered a novel class of inhibitors for both human MetAP1 (HsMetAP1) and human MetAP2 (HsMetAP2). This class of inhibitors contains a pyridinylpyrimidine core. To understand the structure–activity relationship (SAR) and to search for analogues of 2 with greater potency and higher HsMetAP1-selectivity, a total of 58 analogues were acquired through either commercial source or by in-house synthesis and their inhibitory activities against HsMetAP1 and HsMetAP2 were determined. Through this systematic medicinal chemistry analysis, we have identified (1) 5-chloro-6-methyl-2-pyridin-2-ylpyrimidine as the minimum element for the inhibition of HsMetAP1; (2) 5′-chloro as the favored substituent on the pyridine ring for the enhanced potency against HsMetAP1; and (3) long C4 side chains as the essentials for higher HsMetAP1-selectivity. At the end of our SAR campaign, 25b, 25c, 26d and 30a–30c are among the most selective and potent inhibitors of purified HsMetAP1 reported to date. In addition, we also performed crystallographic analysis of one representative inhibitor (26d) in complex with N-terminally truncated HsMetAP1. [Copyright &y& Elsevier]