Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink

The ability to print and pattern all the components that make up a tissue (cells and matrix materials) in three dimensions to generate structures similar to tissues is an exciting prospect of bioprinting. However, the majority of the matrix materials used so far for bioprinting cannot represent the complexity of natural extracellular matrix (ECM) and thus are unable to reconstitute the intrinsic cellular morphologies and functions. Here, we develop a method for the bioprinting of cell-laden constructs with novel decellularized extracellular matrix (dECM) bioink capable of providing an optimized microenvironment conducive to the growth of three-dimensional structured tissue. We show the versatility and flexibility of the developed bioprinting process using tissue-specific dECM bioinks, including adipose, cartilage and heart tissues, capable of providing crucial cues for cells engraftment, survival and long-term function. We achieve high cell viability and functionality of the printed dECM structures using our bioprinting method.open11349353sciescopu

Enhancing 2D Growth of Organic Semiconductor Thin Films with Macroporous Structures via a Small-Molecule Heterointerface

The physical structure of an organic solid is strongly affected by the surface of the underlying substrate. Controlling this interface is an important issue to improve device performance in the organic electronics community. Here we report an approach that utilizes an organic heterointerface to improve the crystallinity and control the morphology of an organic thin film. Pentacene is used as an active layer above, and m-bis(triphenylsilyl) benzene is used as the bottom layer. Sequential evaporations of these materials result in extraordinary morphology with far fewer grain boundaries and myriad nanometre-sized pores. These peculiar structures are formed by difference in molecular interactions between the organic layers and the substrate surface. The pentacene film exhibits high mobility up to 6.3 cm(2)V(-1)s(-1), and the pore-rich structure improves the sensitivity of organic-transistor-based chemical sensors. Our approach opens a new way for the fabrication of nanostructured semiconducting layers towards high-performance organic electronics.X116049Nsciescopu

Therapeutic foam scaffolds incorporating biopolymer-shelled mesoporous nanospheres with growth factors

Here we report a novel therapeutic scaffolding system of engineered nanocarriers within a foam matrix for the long-term and sequential delivery of growth factors. For this, mesoporous silica nanospheres were first functionalized to have enlarged mesopore size (eMSNs, 12.2 nm) and aminated surface, which was then shelled by a biopolymer, poly(lactic acid) (PLA) or poly(ethylene glycol) (PEG) via an electrospraying. The hybrid nanocarrier was subsequently combined with collagen to produce foam scaffolds. Bovine serum albumin (BSA), used as a model protein, was effectively loaded within the enlarged nanospheres. The biopolymer shell substantially prolonged the release period of BSA (over 2-3 weeks from shelled nanospheres vs. within 1 week from bare nanospheres), and the release rate was highly dependent on the shell composition (PEG > PLA). Collagen foam scaffolding of the shelled nanocarrier further slowed down the protein release while enabling the incorporation of a rapidly releasing protein, which is effective for the sequential protein delivery. Acidic fibroblast growth factor (aFGF), loaded onto the shelled-nanocarrier scaffolds, was released over a month at a highly sustainable rate, profiling a similar release pattern to BSA. Biological activity of the aFGF released from the system, as examined by the proliferative potential of osteoblastic precursor cells, showed a significant improvement in the case with aFGF. Furthermore, in vivo implantation of the aFGF-delivering system in a rat subcutaneous tissue for 2 weeks showed a substantially enhanced invasion of fibroblasts with a homogeneous population. Taken together, it is concluded that the biopolymer encapsulation of mesoporous nanospheres effectively prolongs the release of growth factors over weeks to a month, providing a nanocarrier platform for a long-term growth factor delivery, moreover, the foam scaffolding of the nanocarrier system will be a potential therapeutic 3D matrix for cell culture and tissue engineering

Inhibitory Activity of Bevacizumab to Differentiation of Retinoblastoma Cells

Vascular endothelial growth factor (VEGF) is a major regulator in retinal and choroidal angiogenesis, which are common causes of blindness in all age groups. Recently anti-VEGF treatment using anti-VEGF antibody has revolutionarily improved the visual outcome in patients with vaso-proliferative retinopathies. Herein, we demonstrated that bevacizumab as an anti-VEGF antibody could inhibit differentiation of retinoblastoma cells without affection to cellular viability, which would be mediated via blockade of extracellular signal-regulated kinase (ERK) 1/2 activation. The retinoblastoma cells expressed VEGFR-2 as well as TrkA which is a neurotrophin receptor associated with differentiation of retinoblastoma cells. TrkA in retinoblastoma cells was activated with VEGF treatment. Interestingly even in the concentration of no cellular death, bevascizumab significantly attenuated the neurite formation of differentiated retinoblastoma cells, which was accompanied by inhibition of neurofilament and shank2 expression. Furthermore, bevacizumab inhibited differentiation of retinoblastoma cells by blockade of ERK 1/2 activation. Therefore, based on that the differentiated retinoblastoma cells are mostly photoreceptors, our results suggest that anti-VEGF therapies would affect to the maintenance or function of photoreceptors in mature retina

Highly photoresponsive and wavelength-selective circularly-polarized-light detector based on metal-oxides hetero-chiral thin film

A highly efficient circularly-polarized-light detector with excellent wavelength selectivity is demonstrated with an elegant and simple microelectronics-compatible way. The circularly-polarized-light detector based on a proper combination of the geometry-controlled TiO2-SnO2 hetero-chiral thin film as an effective chiroptical filter and the Si active layer shows excellent chiroptical response with external quantum efficiency as high as 30% and high helicity selectivity of similar to 15.8% in an intended wavelength range. Furthermore, we demonstrated the ability of manipulating both bandwidth and responsivity of the detector simultaneously in whole visible wavelength range by a precise control over the geometry and materials constituting hetero-chiral thin film. The high efficiency, wavelength selectivity and compatibility with conventional microelectronics processes enabled by the proposed device can result in remarkable developments in highly integrated photonic platforms utilizing chiroptical responses.1166Ysciescopu

Spin-orbit coupled molecular quantum magnetism realized in inorganic solid

Molecular quantum magnetism involving an isolated spin state is of particular interest due to the characteristic quantum phenomena underlying spin qubits or molecular spintronics for quantum information devices, as demonstrated in magnetic metal-organic molecular systems, the so-called molecular magnets. Here we report the molecular quantum magnetism realized in an inorganic solid Ba3Yb2Zn5O11 with spin-orbit coupled pseudospin-1/2 Yb3+ ions. The magnetization represents the magnetic quantum values of an isolated Yb-4 tetrahedron with a total (pseudo) spin 0, 1 and 2. Inelastic neutron scattering results reveal that a large Dzyaloshinsky-Moriya interaction originating from strong spin-orbit coupling of Yb 4f is a key ingredient to explain magnetic excitations of the molecular magnet states. The Dzyaloshinsky-Moriya interaction allows a non-adiabatic quantum transition between avoided crossing energy levels, and also results in unexpected magnetic behaviours in conventional molecular magnets.1141Ysciescopu

Signal transducer and activator of transcription 3-mediated CD133 up-regulation contributes to promotion of hepatocellular carcinoma

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Moxifloxacin: Clinically compatible contrast agent for multiphoton imaging

Multiphoton microscopy (MPM) is a nonlinear fluorescence microscopic technique widely used for cellular imaging of thick tissues and live animals in biological studies. However, MPM application to human tissues is limited by weak endogenous fluorescence in tissue and cytotoxicity of exogenous probes. Herein, we describe the applications of moxifloxacin, an FDA-approved antibiotic, as a cell-labeling agent for MPM. Moxifloxacin has bright intrinsic multiphoton fluorescence, good tissue penetration and high intracellular concentration. MPM with moxifloxacin was demonstrated in various cell lines, and animal tissues of cornea, skin, small intestine and bladder. Clinical application is promising since imaging based on moxifloxacin labeling could be 10 times faster than imaging based on endogenous fluorescence.1152sciescopu

Agonistic aptamer to the insulin receptor leads to biased signaling and functional selectivity through allosteric modulation

Due to their high affinity and specificity, aptamers have been widely used as effective inhibitors in clinical applications. However, the ability to activate protein function through aptamer-protein interaction has not been well-elucidated. To investigate their potential as target-specific agonists, we used SELEX to generate aptamers to the insulin receptor (IR) and identified an agonistic aptamer named IR-A48 that specifically binds to IR, but not to IGF-1 receptor. Despite its capacity to stimulate IR autophosphorylation, similar to insulin, we found that IR-A48 not only binds to an allosteric site distinct from the insulin binding site, but also preferentially induces Y1150 phosphorylation in the IR kinase domain. Moreover, Y1150-biased phosphorylation induced by IR-A48 selectively activates specific signaling pathways downstream of IR. In contrast to insulin-mediated activation of IR, IR-A48 binding has little effect on the MAPK pathway and proliferation of cancer cells. Instead, AKT S473 phosphorylation is highly stimulated by IR-A48, resulting in increased glucose uptake both in vitro and in vivo. Here, we present IR-A48 as a biased agonist able to selectively induce the metabolic activity of IR through allosteric binding. Furthermore, our study also suggests that aptamers can be a promising tool for developing artificial biased agonists to targeted receptors.111615Ysciescopu

Small intestinal eosinophils regulate Th17 cells by producing IL-1 receptor antagonist

Eosinophils play proinflammatory roles in helminth infections and allergic diseases. Under steady-state conditions, eosinophils are abundantly found in the small intestinal lamina propria, but their physiological function is largely unexplored. In this study, we found that small intestinal eosinophils down-regulate Th17 cells. Th17 cells in the small intestine were markedly increased in the Delta dblGATA-1 mice lacking eosinophils, and an inverse correlation was observed between the number of eosinophils and that of Th17 cells in the small intestine of wild-type mice. In addition, small intestinal eosinophils suppressed the in vitro differentiation of Th17 cells, as well as IL-17 production by small intestinal CD4(+) T cells. Unlike other small intestinal immune cells or circulating eosinophils, we found that small intestinal eosinophils have a unique ability to constitutively secrete high levels of IL-1 receptor antagonist (IL-1Ra), a natural inhibitor of IL-1 beta. Moreover, small intestinal eosinophils isolated from IL-1Ra-deficient mice failed to suppress Th17 cells. Collectively, our results demonstrate that small intestinal eosinophils play a pivotal role in the maintenance of intestinal homeostasis by regulating Th17 cells via production of IL-1Ra.open111815sciescopu