During cancer metastasis, circulating tumor cells constantly experience hemodynamic shear stress in the circulation. Cellular responses to shear stress including cell viability and proliferation thus play critical roles in cancer metastasis. Here, we developed a microfluidic approach to establish a circulatory microenvironment and studied circulating human colon cancer HCT116 cells in response to a variety of magnitude of shear stress and circulating time. Our results showed that cell viability decreased with the increase of circulating time, but increased with the magnitude of wall shear stress. Proliferation of cells survived from circulation could be maintained when physiologically relevant wall shear stresses were applied. High wall shear stress (60.5 dyne/cm 2 ), however, led to decreased cell proliferation at long circulating time (1 h). We further showed that the expression levels of β-catenin and c-myc, proliferation regulators, were significantly enhanced by increasing wall shear stress. The presented study provides a new insight to the roles of circulatory shear stress in cellular responses of circulating tumor cells in a physiologically relevant model, and thus will be of interest for the study of cancer cell mechanosensing and cancer metastasis.Cancer metastasis, a multistep process in which cancer cells migrate or flow from the primary tumor site to a distal location, causes over 90% of cancer-related deaths 1,2 . Over 50% patients with colorectal cancer, for example, develop distant metastasis, making the colorectal cancer the second leading cause of cancer deaths in the United States 2 . During metastasis, circulating tumor cells (CTCs) are transported through the blood circulatory system and are subjected to hemodynamic forces 3 . Although it is known that fluid shear-forces resulted from the bloodstream cause destructions of CTCs and only a small fraction of CTCs can survive and generate metastasis 1,4,5 , the effect of circulatory shear flow on the viability and proliferation of CTCs remains elusive.Progress has been made to understand the mechanism of shear stress in the regulation of cancer cells. However, the majority of studies investigate the effects of shear on cells that are immobilized in micro-wells or adhered to microchannels [6][7][8] . The effect of shear on circulating cancer cells in suspension, however, remains less understood. Approaches, such as cone-and-plate viscometer and stirring bath, have been developed to study the effect of shear on cell suspensions [9][10][11] . However, the shear conditions are less physiologically relevant, and thus are marginally effective to evaluate the effect of circulatory shear stress on CTCs. Most importantly, previous studies have mainly focused on cell viability after shear stimulation 6,9,12 , the proliferation of cells that are survived from shear, which plays an important role in the development of secondary tumors, remains unknown.Here, we developed a microfluidic circulatory system to study the effect of shear stress on the viability an...
Acid and metalliferous release occurring when sulfide (principally pyrite)-containing rock from mining activities and from natural environments is exposed to the elements is acknowledged as a major environmental problem. Acid rock drainage (ARD) management is both challenging and costly for operating and legacy mine sites. Current technological solutions are expensive and focused on treating ARD on release rather than preventing it at source. We describe here a viable, practical mechanism for reduced ARD through the formation of silicate-stabilized iron oxyhydroxide surface layers. Without silicate, oxidized pyrite particles form an overlayer of crystalline goethite or lepidocrocite with porous structure. With silicate addition, a smooth, continuous, coherent and apparently amorphous iron oxyhydroxide surface layer is observed, with consequent pyrite dissolution rates reduced by more than 90% at neutral pH. Silicate is structurally incorporated within this layer and inhibits the phase transformation from amorphous iron (oxy)hydroxide to goethite, resulting in pyrite surface passivation. This is confirmed by computational simulation, suggesting that silicate-doping of a pseudoamorphous iron oxyhydroxide (ferrihydrite structure) is thermodynamically more stable than the equivalent undoped structure. This mechanism and its controlling factors are described. As a consequence of the greatly reduced acid generation rate, neutralization from on-site available reactive silicate minerals may be used to maintain neutral pH, after initial limestone addition to achieve neutral pH, thus maintaining the integrity of these layers for effective ARD management.
3D printing of biological architectures that mimic the structural and functional features of in vivo tissues is of great interest in tissue engineering and the development of transplantable organ constructs. Printable bio-inks that are compatible with cellular activities play critical roles in the process of 3D bio-printing. Although a variety of hydrogels have been used as bio-inks for 3D bio-printing, they inherit poor mechanical properties and/or the lack of essential protein components that compromise their performance. Here, a hybrid Matrigel–agarose hydrogel system has been demonstrated that possesses both desired rheological properties for bio-printing and biocompatibility for long-term (11 days) cell culture. The agarose component in the hybrid hydrogel system enables the maintenance of 3D-printed structures, whereas Matrigel provides essential microenvironments for cell growth. When human intestinal epithelial HCT116 cells are encapsulated in the printed Matrigel–agarose constructs, high cell viability and proper cell spreading morphology are observed. Given that Matrigel is used extensively for 3D cell culturing, the developed 3D-printable Matrigel–agarose system will open a new way to construct Matrigel-based 3D constructs for cell culture and tissue engineering.
Raman spectroscopy is a powerful technique for the study of materials chemistry and nanostructure. This nondestructive technique is highly sensitive to molecular and crystal lattice vibrations, which allow for a comprehensive study of the vibrational modes of molecules incorporated in photovoltaic perovskite materials. In this study, we apply Raman spectroscopy to study FAPbX 3 (X = Cl, Br, I) and FA x MA 1−x PbI 3 (FA stands for formamidinium; MA for methylammonium) metal halide perovskite single crystals and discuss the necessary conditions to obtain reliable data. We establish a correlation between perovskite composition and their unique Raman intensities/spectral shapes. In particular, we show that tuning of the halide content results in a spectral shift of the organic features of the Raman spectrum due to changes in the strength of hydrogen bonding, while tuning of the organic cation is related more to changes in peak intensity. Moreover, the effect of temperature on the vibrational modes corresponding to NCN bending, NH 2 torsion, and NH 2 wagging were studied. This enables the impact of the organic composition in FA x MA 1−x PbI 3 on the phase transition temperature of the material to be determined. Furthermore, we establish links between Raman spectroscopy and other conventional measurement techniques such as X-ray diffraction (XRD) and differential scanning calorimetry (DSC). This study provides insight into the interpretation of the Raman spectra of FA-based perovskites, which furthers understanding of the properties of these materials in relation to their full exploitation in solar cells.
All-solid-state lithium metal batteries are highly attractive because of their high energy density and inherent safety. However, it is still a great challenge to design the solid electrolytes with high ionic conductivity at room temperature and good electrode/electrolyte interfacial compatibility simultaneously in a facile and scalable way. In this work, for the first time, the combination of salt affluent Poly(ethylene oxide) with Li6.75La3Zr1.75Ta0.25O12 nanofibers was designed and intensively evaluated. The synergistic effect of each component in the electrolyte enhances the ionic conductivity to 2.13 × 10–4 S cm–1 at 25 °C and exhibits a high transference number of 0.57. The composite electrolyte possesses superior interfacial stability against Li metal for over 680 h in Li symmetric cells even at a relatively high current density of 2 mA cm–2. The all-solid-state batteries employing the solid electrolytes exhibit excellent cycling stability at room temperature and superior safety performance. This work proposes a brand-new strategy to design and fabricate solid electrolytes in a versatile way for room-temperature all-solid-state batteries.
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