3D Bio-Printed Glioblastoma-Vascular Niche Models

Introduction Glioblastoma multiforme(GBM),a malignant brain tumor,is highly invasive and use brain microvessels to migrate and invade.Studying the perivascular invasion/migration of GBM may enable new possibilities in GBM therapy.However,the lack proper 3D study models that recapitulate GBM hallmarks restricts investigating cell-cell/cell-molecular interactions in tumor microenvironments.In this study,we created GBM-vascular niche models through 3D bioprinting [1-2] using patient-derived GBM cells with sternness(GSC:glioblastoma stem cells),vasculature endothelial cells(ECs),mural cells,and various hydrogels.Materials and methods Three GBM-vascular models were designed:Model A with large vessels and GBM spheroid;Model B with large-and micro-vessels,and GBM spheroid;Model C with large-and micro-vessels and scattered GBM cells.Large channels were created by sacrificial bioprinting.Microvessel network was formed through self-assembly of ECs(HUVEC or brain EC)and mural cells(fibroblast,pericytes,and/or astrocytes).Three GBM cell types were used in the study:SD02 and SD03 are GSCs;U87MG is a commercially-available GBM cell line.Collagen type I or fibrin hydrogel have been used as major scaffold materials.For drug treatment,Temozolomide in culture medium was perfused through large vasculatures in Model A.Results and discussion Three different GBM-vascular models were successfully fabricated and culture for 2-10.GSCs cultured in these models maintained sternness and heterogeneity during the long-term cultures.In Model A,GSCs actively invaded into the surrounding tissues(~Day26),initially regressed in response to the drug(~Day50),then developed therapeutic resistance and resumed aggressive invasion(~Day57).In Model B and C,three GBM types presented distinctive invasion patterns and EC-interactions.SD02 cells showed a spiky invasion pattern with elongated morphology.SD03 cells showed a more dispersed invasion pattern with many single cell migrations towards surrounding microvessels.U87MG cells showed a blunt invasion pattern,caused EC death in the spheroid form;however,the EC death was significantly reduced in the scattered single cell form.Conclusions In this study,we have created GBM-vascular niche models that can recapitulate various GBM characteristics such as cancer sternness,tumor type-specific invasion patterns,and drug responses with therapeutic resistance.Our models have a great potential in investigating patient-specific tumor behaviors under chemo-/radio-therapy conditions and consequentially helping to tailor personalized treatment strategy.The model platform is capable of modifying multiples variables including ECMs,cell types,vascular structures,and dynamic culture condition.Thus,it can be adapted to other biological systems and serve as a valuable tool for generating customized microenvironments.

基于CATIA辅助绑扎件生产设计的方法

针对客滚船船上的绑扎件多,安装精度高导致结构开孔型式复杂且数据较多的问题,利用CATIA辅助绑扎件的生产设计,不仅能充分保证绑扎件开孔精度,还能极大的提高设计效率。

Ultrasensitive detection of micro RNA-21 in human serum based on the confinement effect enhanced chemical etching of gold nanorods

Natural enzymes,such as horseradish peroxidase(HRP),are a class of important biocatalysts with the high specificity,but their catalytic efficiency is usually unsatisfactory.Thus,the higher catalytic efficiency induced by the confinement effect is promising in optical sensing systems.In this work,a dark-field light scattering sensing platform was fabricated by the confinement effect of HRP from hybridization chain reaction(HCR)and then released to solution by the toehold-mediated strand displacement reaction(TSDR).Then,HRP catalyzed the 3,3,5,5-tetramethylbenzidine(TMB)to TMB^(2+)with the assistance of hydrogen peroxide,which etched the gold nanorods(Au NRs)with the weakened light scattering.The single-particle assay was established based on the decreased light scattering intensity of AuNRs under dark-field microscope.The proposed assay revealed excellent analytical performance within a linear range from 25 pmol/L to 600 pmol/L,and a low limit of detection of 3.12 pmol/L.Additionally,it also manifested satisfactory recovery of mi RNA-21 in human serum samples.The high sensitivity,excellent specificity,and universal applicability make this sensing platform promising for disease diagnosis.

A Novel Molecular Imprinted Polymers-Based Lateral Flow Strip for Sensitive Detection of Thiodiglycol

Traditional detection of thiodiglycol(TDG),a metabolic marker for sulfur mustard poisoning,requires not only professional operators,but also expensive reagents and large instruments.Herein,we developed a novel molecular imprinted polymers(MIPs)-based lateral flow assay(LFA)strategy for the quick,sensitive,and selective detection of TDG.Gold nanoparticles(Au NPs),MIPs,and metallothioneins(MTs)were respectively loaded on the conjugate pad,test line(T line)and control line(C line).After adding TDG,Au NPs on the conjugate pad reacted with TDG through the Au-S bond first.Then,under the action of capillary force,the conjugates of TDG and Au NPs were trapped by the MIPs as they traveled to the T line,and the residual Au NPs bound with the MTs on the C line,exhibiting two obvious red bands on T line and C line,respectively.In contrast,a single red band could be observed on C line without TDG.This method exhibited a wide linear range from 10.0 pg/m L to 10,000.0 ng/m L and its limit of detection(LOD)was as low as 0.41 pg/m L.This method was successfully utilized to detect TDG in human urine,presenting significant potential in the point-of-care testing of TDG in clinical samples of the sulfur mustard poisoning patients.

Visually monitoring the etching process of gold nanoparticles by KI/12 at single-nanoparticle level using scattered-light dark-field microscopic imaging

Real-time monitoring of reaction processes is helpful for understanding the reaction mechanisms. In this study we investigated the etching mechanism of gold nanopartides （AuNPs） by iodine on a single-nanopartide level because AuNPs have become important nanoprobes with applications in sensing and bioimaging fields owing to their specific localized surface plasmon resonance （LSPR） properties. By using a scattered-light dark-field microscopic imaging （iDFM） technique, the in situ KI/I2-treated etching processes of various shapes of AuNPs, including nanospheres （AuNSs）, nanorods （AuNRs）, and nanotrigonal prisms （AuNTs）, were monitored in real time. It was found that the scattered light of the different shapes of AuNPs exhibited noticeable color changes upon exposure to the etching solution. The scattering spectra during the etching process showed obvious blue-shifts with decreasing scattered intensity owing to the oxidation of Au atoms into [AuI2]-. Both finite-difference time-domain （FDTD） simulations and monitoring of morphological variations proved that the etching was a thermodynamic-dependent process through a chamfering mechanism coupled with layer-by-layer peeling, resulting in isotropic spheres with decreased particle sizes.

Photoluminescence of carbon quantum dots:coarsely adjusted by quantum confinement effects and finely by surface trap states

Photoluminescence(PL) mechanism of carbon quantum dots(CQDs) remains controversial up to now even though a lot of approaches have been made. In order to do that, herein a PL color ladder from blue to near infrared of CQDs with the absolute quantum yields higher than 70% were prepared via a one-pot hydrothermal synthesis route and separated by silica gel column.Time-correlated single photon counting measurements suggest that the electron transition takes in effect in the PL progress of the crystalline core-shell structured CQDs, and the PL properties could be coarsely adjusted by tuning the size of the crystalline carbon core owing to quantum confinement effects, and finely adjusted by changing the surface functional groups consisted shell owing to surface trap states,respectively. Both coarse and fine adjustments of PL, as optical and photoelectrical characterizations and density-functional theory(DFT) calculations have demonstrated, make it possible for top-level design and precise synthesis of new CQDs with specific optical properties.

Reshaping the chromatin landscape after spinal cord injury

The pathophysiology underlying spinal cord injury is complex. Mechanistic understanding of the adaptive responses to injury is critical for targeted therapy aimed at reestablishing lost connections between proximal and distal neurons. After injury, cell-type specific gene transcription programs govern distinct cellular behaviors, and chromatin regulators play a central role in shaping the chromatin landscape to adjust transcriptional profiles in a contextdependent manner. In this review, we summarize recent progress on the pleiotropic roles of chromatin regulators in mediating the diverse adaptive behaviors of neurons and glial cells after spinal cord injury, and wherever possible, discuss the underlying mechanisms and genomic targets. We specifically draw attention to the perspective that takes into consideration the impact of epigenetic modulation on axon growth potential, together with its effect on woundhealing properties of glial cells. Epigenetic modulation of chromatin state represents an emerging therapeutic direction to promote neural repair and axon regeneration after spinal cord injury.

Large-scale preparation of fernwort-like single-crystalline superstructures of CuSe as Fenton-like catalysts for dye decolorization

A simple green hydrothermal template-free method was developed to prepare single-crystalline superstructures of fern- wort-like copper selenide （CuSe） in large-scale by using polyvinylpyrrolidone （PVP） as both reductant and surfactant for the first time. Time-dependent morphologic evolution was made in order to explore the formation mechanism of the as-prepared product. The copper selenides with different morphologies, phases and structural forms could be prepared by varying the synthesis parameters, such as precursor molar ratios, precursor combinations, and the molecular weight of PVP. The fernwort-like superstructures of CuSe show excellent Fenton-like catalytic activities in degrading malachite green （MG） and rhodamine B （RhB）. These catalysts play an important role in the degradation process of MG and RhB solution with the aid of H202 which can yield highly reactive hydroxyl radicals （HO.）. Besides, the as-prepared CuSe catalyst is stable and reusable, thus it could be applied to the treatment of the dye contaminated waste water.

Mechanism of rhodium(Ⅲ)-catalyzed formal C(sp^3)-H activation/spiroannulation of a-arylidene pyrazolones with alkynes:A computational study

The rhodium-catalyzed formal C（sp^3）-H activation/spiroannulation of α-arylidene pyrazolones with alkynes was investigated by means of density functional theory calculations. The calculations indicate that the spiroannulation through the proposed C-C reductive elimination is kinetically unfeasible, Instead, the C-C coupling from the eight-membered rhodacycle was proposed to account for the experimental results. The overall catalytic cycle consists of six steps： （1） the keto-enol isomerization; （2） the O-H deprotonation, （3） the C（sp^2）-H bond cleavage; （4） the migratory insertion of alkyne into the Rh-C bond; （5） the C-C coupling and （6） the regeneration of the active catalyst.

The Strength behind Submission——A Feminist Interpretation about The Taming of the Shrew

莎士比亚的喜剧《驯悍记》记叙了一位桀骜不驯的少女被训练为一位对丈夫千依百顺的妻子的故事。本剧反映了伊丽莎白时代对于男女的社会角色的定位和女性对于这种定位的反叛。本文将从女性主义的角度入手,从妇女的经济地位,社会习俗在男女行为上的双重标准以及男性对妇女的社会地位和自由的压制来分析女主人公的经历和心理状况,从而揭示女主人公对男权社会的反叛和胜利。