Manipulation of live mouse embryonic stem cells using holographic optical tweezers

We report the ability to move and arrange patterns of live embryonic stem cells using holographic optical tweezers. Single cell suspensions of mouse embryonic stem cells were manipulated with holographic optical tweezers into a variety of patterns including lines, curves and circles. Individual cells were also lifted out of the sample plane highlighting the potential for 3D positional control. Trypan blue dye exclusion and Live/Dead? staining (CMFDA^?1, EthHD^?1) showed that the cells were still viable after manipulation with the optical tweezers. The ability to move individual stem cells into specific, pre-defined patterns provides a method to study how arrangement and associated small-scale interactions occur between neighbouring cells.     

Particle tracking microrheology of cancer cells in living subjects

Cumulative evidence shows that microenvironmental conditions play a significant role in the regulation of cell functions, and how cells respond to these conditions are of central importance to regenerative medicine and cancer cell response to therapeutics. Here, we develop a new method to examine cell mechanical properties by analyzing the motion of nanoparticles in living in mice, combining particle tracking with intravital microscopy. This method directly examines the mechanical response of breast carcinoma cells and normal breast epithelial cells under intravital microenvironments. Our results show both carcinoma and normal cells display significantly reduced compliance (less deformability) in vivo compared to the same cells cultured in 2D, in both sparse and confluent conditions. While the compliance of the normal cells remains steady over time, the compliance of carcinoma cells decreases further as they form tumor-like architectures. Integrating the cancer cells into spheroids embedded in 3D collagen matrices in part redirected the mechanical response to a state closer to the in vivo setting. Overall, our study demonstrates that the microenvironment is a crucial regulator of cell mechanics and the intravital particle tracking method can provide novel insights into the role of cell mechanics in vivo.     

PDMS在阶跃应变中松弛模量与动态剪切中广义弹性模量的比较

本文采用旋转流变仪对比研究了聚二甲基硅氧烷(PDMS)在两平行板间的动态剪切流动和阶跃应变的关系,应用Cho等人提出的应力分解方法考察了大振幅剪切流中的广义弹性模量,发现在线性区及非线性区的一部分,随着角频率ω的增加,在时间尺度为t=1/ω时,大振幅剪切流中的广义弹性模量逐渐接近阶跃应变中的松弛模量。     

树脂基深水浮力材料压缩性能研究

为探究空心微珠填充量对树脂基深水浮力材料压缩性能的影响以及材料压缩破坏机理,基于Mori-Tanaka及Turesanyi方法对空心微珠填充环氧树脂基深水浮力材料的有效弹性模量及压缩强度进行了理论预测.制备了空心微珠填充环氧树脂基深水浮力材料,对不同空心微珠填充比的材料体系进行了单轴压缩试验,并通过扫描电镜观察了材料断裂面微观形貌.结果表明:随着空心微珠填充量增加,材料体系耐压强度降低,模量上升,且实验结果与理论预测吻合情况较好;空心微珠破损是深水浮力材料破坏的根本因素.     

Sigma-2 receptor ligand anchored telmisartan loaded nanostructured lipid particles augmented drug delivery,cytotoxicity, apoptosis and cellular uptake in prostate cancer cells

Recently, the anticancer activity of telmisartan (TEL) has been discovered against prostate cancer. Nevertheless, despite favorable therapeutic profile, poor aqueous solubility and suboptimal oral bioavailability hamper the anticancer efficacy of TEL. Therefore, in this investigation, sigma-2 receptor ligand, 3-(4-cyclohexylpiperazine-1-yl) propyl amine (CPPA) anchored nanostructured lipid particles of telmisartan (CPPA-TEL-NLPs) were engineered using stearic acid for targeting prostate cancer, PC-3 cells. The mean particle size of TEL-NLPs was measured to be 25.4?±?3.2?nm, significantly (p?p?p?In vitro drug release study was conducted to determine the drug delivery potential of tailored nanoparticles. TEL-NLPs released 93.36% of drug significantly (p?50 of CPPA-TEL-NLPs was measured to be 20.3?µM significantly (p?50 of 41.3?µM, significantly (p?>?0.05) not different from 43.4?µM, exhibited by TEL-NLPs in PNT-2 cells. We elucidated that CPPA-TEL-NLPs entered the PC-3 cells via receptor mediated endocytosis pathway and thus exhibited superior cytotoxicity, apoptosis and greater extent of cellular uptake in PC-3 cells. In conclusion, CPPA-TEL-NLPs may be a promising nanomedicine and warrant further in vivo investigations for gaining clinical success.     

低频低能量超声联合微泡对前列腺细胞的影响

目的:采用原子力声显微镜及透射电镜观察低频低能量超声联合微泡对前列腺癌细胞DU145及正常前列腺上皮细胞RWPE-1的作用。方法:两种细胞均分为对照组、单纯超声组、超声联合微泡组。对照组加入一定比例的生理盐水,不进行超声辐照;单纯超声组加入相同比例的生理盐水,用发射频率为21 k Hz的低频超声辐照,辐照2 min,占空比30%;超声联合微泡组加入同前相同比例的微泡造影剂悬浊液,用与单纯超声组相同的超声辐照。处理过的细胞立即用原子力声显微镜观察其形貌并计算其杨氏模量。同时,对同一处理方式的对照组及超声联合微泡组细胞继续培养24 h后,用透射电镜观察细胞。结果:单纯超声组的DU145细胞及RWPE-1细胞的细胞形态与对照组无明显变化;超声联合微泡组的DU145细胞及RWPE-1细胞形态呈类圆形,细胞表面可见放射状显微丝状结构,细胞膜表面可见多个大孔状结构;超声联合微泡组的DU145细胞的弹性模量较RWPE-1细胞大,且与对照组相比,两种细胞的弹性模量均变大,DU145细胞尤甚。透射电镜观察结果示对照组的两种细胞未见细胞自噬,而超声联合微泡组两种细胞都出现自噬现象,其中DU145细胞中可见凋亡现象。结论:低频低能量超声联合微泡可引起前列腺癌DU145细胞及正常前列腺上皮RWPE-1细胞的细胞膜出现孔状结构,并诱导其自噬,且对DU145细胞的损伤大于RWPE-1细胞。     

Three‐Dimensional Exploration and Mechano‐Biophysical Analysis of the Inner Structure of Living Cells

A novel mechanobiological method is presented to explore qualitatively and quantitatively the inside of living biological cells in three dimensions, paving the way to sense intracellular changes during dynamic cellular processes. For this purpose, holographic optical tweezers, which allow the versatile manipulation of nanoscopic and microscopic particles by means of tailored light fields, are combined with self‐interference digital holographic microscopy. This biophotonic holographic workstation enables non‐contact, minimally invasive, flexible, high‐precision optical manipulation and accurate 3D tracking of probe particles that are incorporated by phagocytosis in cells, while simultaneously quantitatively phase imaging the cell morphology. In a first model experiment, internalized polystyrene microspheres with 1 μm diameter are three‐dimensionally moved and tracked in order to quantify distances within the intracellular volume with submicrometer accuracy. Results from investigations on cell swelling provoked by osmotic stimulation demonstrate the homogeneous stretching of the cytoskeleton network, and thus that the proposed method provides a new way for the quantitative 3D analysis of the dynamic intracellular morphology.     

肿瘤干细胞活体示踪的分子影像学研究进展

肿瘤干细胞(Cancer Stem Cell,CSCs)是肿瘤细胞中具有自我更新和多向分化能力的细胞,与肿瘤的发生、增殖、转移和耐药等生物学行为关系密切,CSCs的活体示踪对于实时监测CSCs在体内的生物学行为具有重要意义。目前常见CSCs活体示踪的分子影像学方法包括:超声成像、核磁共振成像(Magnetic Resonance Imaging,MRI)、光学成像、核医学成像(Positron Emission Tomography-Computed Tomography,PET-CT)、光声成像、多模态成像。这些成像方法的发展对于CSCs的研究具有重大意义,对于CSCs的研究有助于临床诊断及治疗,有利于诊疗一体化进程的发展。文章就CSCs活体示踪的分子影像学研究进展进行了综述。     

Measurement of the average shear rate around a microparticle in the shear thinning medium with laser tweezers

A novel method for the determination of the average shear rate around a microparticle moving in the fluid is presented. Although the shear rate around a particle moving in the fluid is a parameter of paramount importance in sedimentation studies, its determination is time-consuming, thus model-based solutions are preferred. However, the current literature models require still rigorous validation. The presented technique relies on optical tracking of a laser-tweezers trapped particle suspended in the liquid medium. The obtained experimental results for spherical particles of 1 micron diameter show a good agreement with the classical rheology and literature correlation models. The new method is a valuable tool for determination of sedimentation parameters as it reduces the time of experiments and the sample volume by order(s) of magnitude when compared to classical methods.     

Substrate-induced phenotypic switches of human smooth muscle cells: an in vitro study of in-stent restenosis activation pathways

In-stent restenosis is a clinical complication following coronary angioplasty caused by the implantation of the metal device in the atherosclerotic vessel. Histological examination has shown a clear contribution of both inflammatory and smooth muscle cells (SMCs) to the deposition of an excess of neointimal tissue. However, the sequence of events leading to clinically relevant restenosis is unknown. This paper aims to study the phenotype of SMCs when adhering on substrates and exposed to biochemical stimuli typical of the early phases of stent implantation. In particular, human SMC phenotype was studied when adhering on extracellular matrix-like material (collagen-rich gel), thrombus-like material (fibrin gel) and stent material (stainless steel) in the presence or absence of a platelet-derived growth factor (PDGF) stimulus. Cells on the collagen and fibrin-rich substrates maintained their contractile phenotype. By contrast, cells on stainless steel acquired a secretory phenotype with a proliferation rate 50 per cent higher than cells on the natural substrates. Cells on stainless steel also showed an increase in PDGF-BB receptor expression, thus explaining the increase in proliferation observed when cells were subject to PDGF-BB stimuli. The stainless steel substrate also promoted a different pattern of β1-integrin localization and an altered expression of hyaluronan (HA) synthase isoforms where the synthesis of high-molecular-weight HA seemed to be favoured. These findings highlighted the induction of a phenotypic pattern in SMC by the stainless steel substrate whereby the formation of a HA-rich neointimal tissue is enhanced.     

碳纳米管聚合物复合材料弹性模量预测模型研究进展

碳纳米管具有优异的力学、电学、光学和磁学等性能,是聚合物复合材料理想的增强体。弹性模量是材料重要的力学性能参数之一,本文介绍了近年来碳纳米管聚合物复合材料弹性模量的研究状况,综述了混合法则、Hashin-Shtrikman模型、Cox模型、Halpin-Tsai模型和数值模拟法预测碳纳米管聚合物复合材料弹性模量的方法,并提出了研究中面临的一些问题以及发展方向。     

Facile development,characterization, and evaluation of novel bicalutamide loaded pH-sensitive mesoporous silica nanoparticles for enhanced prostate cancer therapy

It is a challenge to deliver therapeutics exclusively to cancer cells, while sparing the normal cells. However, pH-sensitive delivery systems have proved to be highly efficient in fulfilling this task due to their ability to provide on-demand and selective release of drug at acidic tumor sites. As a proof of concept, here pH responsive drug delivery system based on mesoporous core shell nanoparticles (NPs) surrounded with poly acrylic acid (PAA) layers were prepared employing a facile synthesis strategy. Bicalutamide (BIC) was encased into surface functionalized MCM-41 nanoparticles via electrostatic interactions. The synthesized NPs were characterized by nitrogen adsorption and desorption isotherms, SEM-EDS, TEM, LXRD, and WXRD. In vitro release studies demonstrated that BIC-MSN-PAA NPs exhibited a higher release in the acidic media which varied inversely with the increase in pH. Further, the results of cell cytotoxicity assay were evident that BICMSNs exhibited more potent killing of both PC-3 and LNCaP cells than free BIC. PAA-MSNs also exhibited an enhanced cellular uptake and prolonged circulation time in vivo. The results are suggestive of the fact that PAA functionalized MSNs can serve as an effective pH-responsive template and hold a great potential ahead in controlled release and effective cancer treatment.     

Further developments in testing and analysis of the plate twist test for in-plane shear modulus measurements

The plate twist test for testing the in-plane shear modulus of composite materials is analysed. In the proposed test set-up the loads are not applied to the corners of the plate. This makes the test easier to perform than the original plate twist test. Based on a strength of materials approach, an analytical expression is found for the correction factor that accounts for the shifted position of the loading points. The analysis is made without making the assumption of equal bending stiffness in the diagonal directions of the plate, and can thus be applied for off-axis tests on orthotropic or lower symmetry composite materials.     

10CrNiMo结构钢弹性模量在低周疲劳过程中的变化规律

采用横截面为圆形的光滑试样,在六级轴向系列不同恒应变幅(0.3%~1.0%)控制下,研究10CrNiMo结构钢弹性模量在低周疲劳过程中的变化规律.结果显示:在不同级别应变幅控制下,随着应变幅值的增加,稳定循环下的弹性模量并不是恒量,而是以负幂指数函数规律减小,且最小与最大应变幅下的弹性模量相差超过15%;而在某一恒应变幅控制下的稳定循环区间内,弹性模量随着循环次数的增加而缓慢下降,但在疲劳失稳时,弹性模量迅速大幅降低.分析认为,出现上述现象的原因,与不同应变幅对材料造成不同程度的疲劳损伤及恒定应变幅控制下材料固有的持续疲劳抗力有关.     

再生混凝土力学性能的研究进展

再生混凝土的应用,不仅能够解决废弃混凝土处理问题;又能降低因资源过度开采所引起的生态环境破坏,因而具有广阔的发展前景。相比于普通混凝土,再生混凝土的抗压强度、弹性模量以及抗疲劳性能较低,主要与再生骨料多方面因素的影响有关。对近年来再生混凝土力学性能相关研究进展进行了综述,再生骨料总吸水率是降低抗压强度的主要原因,疲劳性能则主要与再生骨料取代率和附着砂浆含量有关。在再生混凝土中掺加矿物掺合料能够改善新、旧双界面从而提高抗压强度和劈裂抗拉强度,掌握多个因素的影响和作用对再生骨料和再生混凝土进一步研究和应用具有重要意义。     

Biogenic silver embedded magnesium oxide nanoparticles induce the cytotoxicity in human prostate cancer cells

This work reports the synthesis, characterization, and cytotoxicity of biogenic magnesium oxide nanoparticles (MgONPs) and nanosilver embedded magnesium oxide nanoparticles (Ag-MgONPs). The formation of nanoparticles (NPs) was confirmed by the indications of color changes and precipitations. Field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD) pattern studies showed the agglomeration colloids, porous, spherical, needle-shaped and crystal nature of MgONPs, whereas, the Ag-MgONPs was hexagonal, and spherical structured nanocrystals. Energy-dispersive X-ray fluorescence spectrometry (EDS) study indicated the existence of Ag, Mg, and O in NPs complex. The particle size analysis (PSA) revealed the mean size of 15.09?nm for Ag-MgONPs and 13.68?nm for MgONPs. Fourier transform infrared spectroscopy (FTIR) showed the peaks corresponding to amide, carboxylic acids, aromatics, alkene and esters from mycelial cell-free extract (MCFE). The absorbed and lattices oxygen of MgO was probably assigned in the formation of Ag-MgONPs as indicated by X-ray photoelectron spectroscopy (XPS). Cytotoxicity assay showed the Ag-MgONPs was stronger in inducing the prostate cancer (PC-3) cell death than the MgONPs. This work concluded that Ag-MgONPs could be potential therapeutics for cancer therapy.     

压铸态SiCw/6061Al复合材料中弹性模量的不均匀性

借助图象仪与扫描电镜联机系统，测量压铸态SiCw/6061Al复合材料中的晶须取向分布。基于剪滞后模型及晶须的实际分布情况，分析复合材料弹性模量的不均匀性，采用超声声速法，测量复合材料的弹性模量。结果表明，压铸态复合材料中晶须在垂直压铸方向具有一定择优取向性，晶须体积分数越高其择优取向程度越明显，从而造成复合材料各向弹性模量的不均匀性，试验结果与理论计算基本吻合。     

Development of drug-loaded chitosan hollow nanoparticles for delivery of paclitaxel to human lung cancer A549 cells

In this study, biodegradable chitosan hollow nanospheres (CHN) were fabricated using polystyrene nanospheres (PS) as templates. CHN were applied to increase the solubility of poorly water-soluble drugs. The lung cancer drug paclitaxel (PTX), which is used as a model drug, was loaded into CHN by the adsorption equilibrium method. The drug-loaded sample (PTX-CHN) offered sustained PTX release and good bioavailability. The state characterization of PTX by differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) showed that the PTX absorbed into CHN existed in an amorphous state. An in vitro toxicity experiment indicated that CHN were nontoxic as carriers of poorly water-soluble drugs. The PTX-CHN produced a marked inhibition of lung cancer A549 cells proliferation and encouraged apoptosis. A cell uptake experiment indicated that PTX-CHN was successfully taken up by lung cancer A549 cells. Furthermore, a degradation experiment revealed that CHN were readily biodegradable. These findings state clearly that CHN can be regarded as promising biomaterials for lung cancer treatment.     

同一硫酸盐环境下地聚物混凝土与普通混凝土的耐蚀性能及机理分析

实验采用国家标准GB/T 50082-2009中推荐的混凝土抗硫酸盐侵蚀试验方法,将粉煤灰基地聚物混凝土(FGC)和普通混凝土(PCC)试样置于质量分数为5%的硫酸钠溶液中进行干湿循环侵蚀实验。以试样侵蚀后的结构形态变化、抗压强度损失、质量体积变化、动弹性模量变化为评价指标,并借助扫描电子显微镜(SEM)、X射线能谱(EDS)、电感耦合等离子体发射光谱(ICP-OES)等分析手段对FGC与PCC在同一硫酸盐侵蚀环境中的耐蚀性能、损伤机理以及两者间的相互影响进行了研究与分析。结果显示,随着侵蚀周期的增长两种混凝土的抗压强度和体积均表现出先降低后上升的趋势;二者的最大质量变化率均较小,FGC为0.3%,PCC为0.6%;二者的动弹性模量变化均较为复杂。微观观测发现影响FGC和PCC结构形态的关键物质分别是粉煤灰颗粒与膨胀性产物。化学分析表明FGC与PCC间产生相互影响的原因是材料各组分在侵蚀液中的溶解与渗透。     

Investigation of the Young''s modulus of TiB needles in situ produced in titanium matrix composite

In situ Ti/TiB composites with different volume fractions of discontinuous TiB reinforcements were produced by powder metallurgy. After compacting Ti+TiB₂ powders by hot unidirectional pressure, heat treatments led to the in situ formation of distinctive needles of TiB, randomly distributed in the titanium matrix. The Young's modulus of TiB was evaluated using the ASW computation method and experimental Vickers micro-indentation. Three point bend tests were performed on Ti/TiB composites as a function of the TiB volume fraction in order to extract the Young's modulus of TiB from the elastic properties of the composite. The different values obtained according to these three methods were discussed and compared with the literature.