Search

Tumor-targeted core-shell nanoparticles were developed for a multifunctional drug delivery system (DDS) for cancer therapy. Fe3O4 nanoparticles with mesoporous silica (Fe3O4NPs@mSiO2), in which Fe3O4 and mSiO2 form the core and shell, respectively, were functionalized to deliver a hydrophobic anti-tumor drug and to heat targeted tumor cells with the energy of an alternating magnetic field. For targeting tumor cells, tLyP-1, a tumor cell homing and penetrating peptide, was engrafted on to the Fe3O4NPs@mSiO2 (Fe3O4NPs@mSiO2-tLyP-1). The fabricated Fe3O4NPs@mSiO2-tLyP-1 were loaded with camptothecin (CPT); they showed robust, selective targeting and penetrating efficacy for Hela cells, and induced cell death. The CPT-loaded Fe3O4NPs@mSiO2-tLyP-1 (Fe3O4NPs@mSiO2-tLyP-1(CPT)) reduced the cell viability of Hela cells to 28.8%. Furthermore, in combination with application of an alternating magnetic field to cause hyperthermia, the nanoparticles made it possible to decrease viability to 18.3%. The systemic toxicity of Fe3O4NPs@mSiO2-tLyP-1(CPT) to human mesenchymal stem cells (hMSCs) was minimal, because the nanoparticles selectively targeted and penetrated the tumor cells. This study indicates that the developed Fe3O4NPs@mSiO2-tLyP-1 have potential as a DDS in the chemo-hyperthermic treatment of cancer.

Accidental chemotherapy extravasation exacerbates the side effects of anticancer drugs. Therefore, drug-delivery nanocarriers should be designed to avoid persistent drug release at off-target sites and promote burst drug release at on-target. Considering these requirements, poly(allylamine)-co-poly(allylurea) (PAU), a ureido-derivatized temperature responsive polymer with upper critical solution temperature (UCSTs), is an ideal material. This report describes the fabrication, characterization, and in vitro cellular toxicity of PAU polymer-grafted magnetic mesoporous silica nanoparticles as drug-delivery nanocarriers. A UCST of 43 °C and an ultranarrow transition temperature range of 39-43 °C was realized, ensuring that the nanocarriers suppressed undesirable leakage to below 10 % of the drug loading for 8 h in the absence of a thermal stimulus. A drug release burst of up to 75 % of the drug loading was achieved within 30 min after the stimulus, reducing the viability of the in vitro cancer cells to 12 %. Therefore, the ureido-derivatized polymer is one of the most suitable gatekeepers for drug-delivery nanocarriers.

Under the upgrade program of an azimuthally varying field (AVF) cyclotron in progress at the Research Center for Nuclear Physics (RCNP), an emittance monitor is being developed to improve the beam injection efficiency from ion sources to the AVF cyclotron. In order to evaluate the quality of the beams extracted from ion sources quickly, we developed the Pepper-Pot type Emittance Monitor at the RCNP. After improving an analysis method for emittance estimation using LabVIEW, we achieved a measurement frequency of 4 Hz.

To investigate the impact of secreted factors of rat bone marrow mesenchymal stem cells (MSCs) on the proliferation and migration of tenocytes and provide evidence for the development of MSC-based therapeutic methods of tendon injury. Rat bone marrow mesenchymal stem cell-derived conditioned medium (MSC-CM) promoted the proliferation of tenocytes within 24 h and decreased the percentage of tenocytes in G1 phase. MSC-CM activated the extracellular signal-regulated kinase1/2 (ERK1/2) signal molecules, while the ERK1/2 inhibitor PD98059 abrogated the MSC-CM-induced proliferation of tenocytes, decreased the fraction of tenocytes in the G1 phase and elevated p-ERK1/2 expression. Furthermore, MSC-CM promoted the migration of tenocytes within 6 h, enhanced the formation of filamentous actin (F-actin) and increased the cellular and nuclear stiffness of tenocytes. MSC-CM promotes tenocyte proliferation by changing cell cycle distribution via the ERK1/2 signaling pathway. MSC-CM-induced tenocyte migration was accompanied by cytoskeletal polymerization and increases in cellular and nuclear stiffness.

We investigate the effect of pulsed electric current on fatigue-crack growth and the fatigue properties of aluminum alloy (A6061-T6) at current densities of 0–150 A/mm2. The fatigue life of most of the treated specimens increases substantially when compared with that of untreated specimens. SEM imaging of the treated specimens shows local melting on the fracture surfaces. To clarify the effect of local melting on fatigue-crack propagation, we examine crack propagation utilizing the plastic replication method. We find that the delay of crack propagation is attributable to the crack-shielding effect arising from current-induced local melting.

Migration of bone marrow-derived mesenchymal stem cells (BMSCs) plays an important role in many physiological and pathological settings, including wound healing. During the migration of BMSCs through interstitial tissues, the movement of the nucleus must be coordinated with the cytoskeletal dynamics, which in turn affects the cell migration efficiency. Our previous study indicated that osteopontin (OPN) significantly promotes the migration of rat BMSCs. However, the nuclear behaviors and involved molecular mechanisms in OPN-mediated BMSC migration are largely unclear. In the present study, using an atomic force microscope (AFM), we found that OPN could decrease the nuclear stiffness of BMSCs and reduce the expression of lamin A/C, which is the main determinant of nuclear stiffness. Increased lamin A/C expression attenuates BMSC migration by increasing nuclear stiffness. Decreased lamin A/C expression promotes BMSC migration by decreasing nuclear stiffness. Furthermore, OPN promotes BMSC migration by diminishing lamin A/C expression and decreasing nuclear stiffness via the FAK-ERK1/2 signaling pathway. This study provides strong evidence for the role of nuclear mechanics in BMSC migration as well as new insight into the molecular mechanisms of OPN-promoted BMSC migration.

In this research, we propose a new simple method to fabricate high-density Fe2O3 nanowire arrays for solar water splitting, based on oxidation-assisted stress-induced atomic-diffusion. In the presence of water vapor, surface oxidation was promoted during the heating process. The driving force induced by the stress gradient was enhanced due to the expansion of the oxidation layer. Therefore, Fe2O3 nanowire arrays were fabricated at a relative low temperature (350 °C) with a high density (8.66 wire per μm2). Using the nanowire array as the photoanode, a photocurrent density of 0.65 mA cm−2 at 1.23 V vs. RHE was achieved in a three-electrode system.

Purpose The purpose of this study was to compare the usefulness of measuring acetabular anterior coverage by tomosynthesis and false profile (FP) radiography. Methods 70 hips in 35 patients who were diagnosed with early stage osteoarthritis of the hip, and 60 hips from 30 healthy volunteers were analysed. Plain FP radiographs were taken, and vertical-centre-anterior margin (FP-VCA) angles were measured. Acetabular anterior coverage was measured in the natural standing position using a tomosynthesis imaging system in the sagittal plane. As with FP radiography, we measured vertical-centre-anterior margin (TS-VCA) angles. Results The median values of the FP-VCA angle, and TS-VCA angle were 43.8°, 54.4°, respectively. The TS-VCA angle was significantly larger than the FP-VCA angle. For FP radiographs, the intraobserver intraclass correlation coefficient (ICC) was 0.68, and the interobserver ICC was 0.79. For tomosynthesis sagittal images, the intraobserver ICC was 0.85, and the interobserver ICC was 0.92. There was a strong positive correlation between the TS-VCA angle and the FP-VCA angle. When the FP-VCA angle was 25°, the TS-VCA angle was 35° in regression analysis. Conclusions Measuring acetabular anterior coverage using sagittal plane tomosynthesis correlates well with FP radiography. Regardless of the presence of acetabular deformities, tomosynthesis demonstrated high reproducibility, simple posture setting, low effective doses, and high versatility. A cut-off value of 35° was useful for the detection of developmental dysplasia of the hip joint using the TS-VCA angle.

We report a non-contact and quantitative method to measure the local permittivity of dielectric materials with a nanometer-scale spatial resolution. A theoretical model based on near-field approximation was developed to describe the effect of a microwave on the interaction between a probe and a sample. Under the non-contact mode, we successfully measured the force curves of Si, Al2O3, Ge, and ZrO2 using microwave atomic force microscopy and observed the variation in the force caused by the microwave. According to the established theoretical model, a quantitative non-contact evaluation of the local permittivity of dielectric materials was performed.We report a non-contact and quantitative method to measure the local permittivity of dielectric materials with a nanometer-scale spatial resolution. A theoretical model based on near-field approximation was developed to describe the effect of a microwave on the interaction between a probe and a sample. Under the non-contact mode, we successfully measured the force curves of Si, Al2O3, Ge, and ZrO2 using microwave atomic force microscopy and observed the variation in the force caused by the microwave. According to the established theoretical model, a quantitative non-contact evaluation of the local permittivity of dielectric materials was performed.

Surface-mount techniques primarily depend on soldering. However, soldering techniques have encountered some challenges in recent years. These challenges include rare metal recycling, thermal problems, and Pb toxicity. We recently developed a metallic nanowire surface fastener (NSF) to resolve the abovementioned problems. This fastener can be used to connect electronic components on a substrate at room temperature using the van der Waals force between each nanowire. This study demonstrates a 64-pin NSF that behaves like a ball grid array (BGA) for application to actual electronic devices. The adhesion strength and electrical properties of the NSF were investigated by adjusting the nanowire parameters, such as diameter, length, density (number per area), preload, and shape. The shape control of the nanowires greatly contributed to the improvement of the properties. A maximum adhesion strength of 16.4 N/cm2 was achieved using a bent, hook-like NSF. This strength was 4–5 times the value of the straight NSF. The contact resistivity was 2.98 × 10−2 Ω∙cm2. The NSF fabricated through the simple template method showed the room temperature bonding ability and adaptability to a highly ordered electrode like the BGA.

In recent years, different types of techniques have been developed to observe the cells and extract a wealth of information about their physiological properties. The analysis of the electrical properties requires modeling the cells. However, the cells have complex structures and most of the analytical equations are limited. Therefore, in this laboratory, the microwave detection system is combined with the atomic force microscopy (AFM) to evaluate the local electrical properties of the materials. In this research, a new method to measure the dielectric constant of biomaterials based on microwave was developed on microwave atomic force microscopy (M-AFM). The theoretical model was established to analyze the mechanism of the force caused by microwave and was developed a method to quantitatively measure the dielectric constant. By using this measurement method, the dielectric constant of mesenchymal stem cells (MSCs) was measured.

In this study, a non-contact and quantitative evaluation method was developed to measure the conductivity of metallic nanowires with a nanometer-scale spatial resolution. A coaxial probe was experimentally fabricated; using this probe, microwave images of the Al, Ag, and Cu nanowires and their topography images were simultaneously obtained via microwave atomic force microscopy (M-AFM) in the non-contact mode. A semi-near-field reflection model was established to describe the spatial distribution of a microwave between the tip of the probe and the sample. The local conductivities of metallic nanowires on the nanometer-scale can be quantitatively evaluated in a single scan, using a metal strip substrate to calibrate the reflection signal.

In this paper, we report a non-contact and quantitative method to evaluate the permittivity of semiconductor nanomaterials. A microwave atomic force microscopy (M-AFM) was used to obtain the topography and microwave images of nanomaterials in one scanning process. Morphology and microwave images of ZnO and CuO nanowires, and SnO2 nanobelts with high spatial resolution were obtained in the non-contact mode of M-AFM. The local relative permittivity of these one-dimensional metal oxide nanomaterials was quantitatively evaluated.

In this paper, we have proposed a new crystal plane control technique of single crystal SnO2 nanobelts by thermal sublimation. The synthesis pressure was found to drastically influence the dimension of the cross-sectional aspect ratio (width–thickness) of the nanobelts. The pressure changed the surface free energy that contributes to the preferential growth of crystal planes of the nanobelt. The aspect ratio range of 1.2 to 7.39 for the nanobelts was achieved solely owing to the pressure variation. Also, as a catalyst style on the synthesis by thermal sublimation, the dispersed Au nanoparticles assisted the formation of uniform SnO2 nanobelts.

Cells maintain homeostasis and perform various functions by interacting mechanically with a cell-adhesive matrix. Regarding cellular differentiation, it has been found that matrix elasticity can determine the differentiation lineage of mesenchymal stem cells (MSCs). Direct quantitative measurements of the mechanical interaction between MSCs and matrix for differentiation, however, have yet to be reported. Herein, the displacement field of the cell-adhesive matrix was observed quantitatively using a digital volume correlation (DVC) method. Maximum displacement and cellular traction stress were analyzed when the MSC differentiated into a neuron-like cell or an osteoblast-like cell on a soft or hard elastic matrix, respectively. The function of non-muscle myosin II (NMM II), which plays an important role in intracellular cytoskeletal dynamics, was investigated during cellular differentiation. The mechanical interaction (maximum displacement and subjected area of the matrix) between the cell and matrix was dependent on matrix elasticity. It has also been shown that the mechanical interaction between the intracellular cytoskeleton and cell-adhesion matrix is indispensable for cellular differentiation. This work provides the first quantitative visualization of the mechanical interaction between MSCs and the cell-adhesion matrix for differentiation.

The growth of fatigue crack in aluminum alloy, 6061-T6, under the application of pulsed electric current was studied. To examine the effect of pulsed electric current, different electric current densities were used at different fatigue cycles, where the electric current densities were subjected as 90 A/mm2 and 150 A/mm2. With the electric current density of 90 A/mm2, the fatigue life was increased. However, when the current density levels became higher, that is, 150 A/mm2, the fatigue life was decreased. From the fracture surface observations, the local melting was found on crack surface. It is concluded that the increase of fatigue life is attributed to the crack shielding effect resulted from the local melting induced by the pulsed electric current. In addition, the effect of pulsed electric current was more remarkable in small crack region.

We previously reported that reducing-environment-responsive prodrug-type small interfering RNA (siRNA) bearing 2′-O-methyldithiomethyl (2′-O-MDTM) uridine exhibits efficient knockdown activity and nuclease resistance. In this report, we describe the preparation of 2′-O-MDTM oligonucleotides modified not only at uridine but also at adenosine, guanosine and cytidine residues by post-synthetic modification. Precursor oligonucleotides bearing 2′-O-(2,4,6-trimethoxybenzylthiomethyl) (2′-O-TMBTM) adenosine, guanosine, and cytidine were reacted with dimethyl(methylthio)sulfonium tetrafluoroborate to form 2′-O-MDTM oligonucleotides in the same manner as the oligonucleotide bearing 2′-O-TMBTM uridine. Furthermore, the oligonucleotides bearing 2′-O-MDTM adenosine, guanosine, and cytidine were efficiently converted into corresponding natural 2′-hydroxy oligonucleotides under the cytosol-mimetic reducing condition.

The market for wearable devices has increased considerably in recent years. In response to this demand, flexible electronic circuit technology has become more important. The conventional bonding technology in electronic assembly depends on high-temperature processes such as reflow soldering, which result in undesired thermal damages and residual stress at a bonding interface. In addition, it exhibits poor compatibility with bendable or stretchable device applications. Therefore, there is an urgent requirement to attach electronic parts on printed circuit boards with good mechanical and electrical properties at room temperature. Nanowire surface fasteners (NSFs) are candidates for resolving these problems. This paper describes the fabrication of an NSF on a flexible substrate, which can be used for room temperature conductive bonding. The template method is used for preparing high-density nanowire arrays. A Cu thin film is layered on the template as the flexible substrate. After etching the template, a Cu NSF is obtained on the Cu film substrate. In addition, the electrical and mechanical properties of the Cu NSF are studied under various fabrication conditions. The Cu NSF exhibits high shear adhesion strength (~234 N cm^−2) and low contact resistivity (2.2 × 10^−4 Ω cm2)., ファイル公開：2019-07-27

There is a need for efficient stem cell-to-tenocyte differentiation techniques for tendon tissue engineering. More than 1 week is required for tenogenic differentiation with chemical stimuli, including co-culturing. Research has begun to examine the utility of mechanical stimuli, which reduces the differentiation time to several days. However, the precise length of time required to differentiate human bone marrow-derived mesenchymal stem cells (hBMSCs) into tenocytes has not been clarified. Understanding the precise time required is important for future tissue engineering projects. Therefore, in this study, a method was developed to more precisely determine the length of time required to differentiate hBMSCs into tenocytes with cyclic stretching stimulus.First, it had to be determined how stretching stimulation affected the cells. Microgrooved culture membranes were used to suppress cell orientation behavior. Then, only cells oriented parallel to the microgrooves were selected and evaluated for protein synthesis levels for differentiation.The results revealed that growing cells on the microgrooved membrane and selecting optimally-oriented cells for measurement improved the accuracy of the differentiation evaluation, and that hBMSCs differentiated into tenocytes in approximately 10 h.The differentiation time corresponded to the time required for cellular cytoskeleton reorganization and cellular morphology alterations. This suggests that cells, when subjected to mechanical stimulus, secrete mRNAs and proteins for both cytoskeleton reorganization and differentiation.

At the new DC muon beamline MuSIC at Research Center for Nuclear Physics (RCNP), Osaka University, the beamline construction from the solenoid system of the muon production to the experimental port was completed. A beamline commissioning and a feasibility study for μSR are now in progress. With newly refurbished spectrometer installed at the experimental port, we succeeded in observing μSR spectra and μ-e decay asymmetry in a simple setup down to 4 K. We are still under development of other μSR appratuses.

In this study, we successfully fabricated a single-crystal Fe 2 O 3 nanowire array based on stress-induced atomic diffusion and used this array as the photoelectrode for solar water splitting. With the surface polishing treatment on the sample surface, the density of the Fe 2 O 3 nanowire array reached up to 28.75 wire µm −2 when heated for 90 min at 600°C. The photocurrent density of the optimized sample was 0.9 mA cm −2 at 1.23 V versus a reversible hydrogen electrode in a three-electrode system under AM 1.5 G illumination. The incident photon-to-electron conversion efficiency was 6.8% at 400 nm.

To develop a new co-culture system, the separable-close co-culture system, to replace the indirect co-culture system which analyzes cellular interactions between two groups of cells with each type being cultured separately and also the direct co-culture system where the two cell types are cultured together. The new system not only achieved effective cellular interactions but also allowed the effect that one group of cells has on another group of cells to be evaluated. We performed co-culturing of human bone marrow mesenchymal stem cells and human articular chondrocytes using the new system. The new system made it possible to assess separately the effects of one group of cells on the other cell type, as in the indirect co-culture system. Furthermore, the new system rivaled or surpassed other co-culture systems in terms of the chondrogenic gene expression. The new co-culture system is effective in terms of assessing gene expression in two cell types.

Cells maintain homeostasis and express various functions by interacting mechanically with cell-adhesive matrix. As regarding cellular differentiation, it has been found that elasticity of the matrix determines differentiation lineage of mesenchymal stem cells (MSCs). The direct quantitative measurement of the mechanical interaction between MSC and matrix for differentiation, however, has not been performed. In the present work, the displacement field of the cell-adhesive matrix was observed quantitatively using digital volume correlation (DVC) method. In practice, the cellular traction stress was analyzed when the MSC differentiated into neuron or osteoblast on the soft or hard elastic matrix, respectively. Then, function of non-muscle myosin II (NMM II), which plays an important role in intracellular cytoskeletal dynamics, was investigated in cellular differentiation. As a result, the mechanical interaction between the cell and the matrix was dependent upon the elasticity of the matrix. Additionally, it has been shown that mechanical interaction between intracellular cytoskeleton and cell-adhesion matrix is indispensable for cellular differentiation.

Tissue engineering is an ideal therapeutic strategy for the development of functional tendon replacement tissue for tendon repair in the clinic. Currently, the synergistic roles of mechano-chemical factors and the mechanisms involved in tendon repair and regeneration are not fully understood. In this study, we developed a three-dimensional (3D) culture system based on a silicone chamber and collagen sponge scaffold that can deliver cyclic mechanical stretch and biochemical stimulation to bone marrow-derived mesenchymal stem cells (BMSCs) seeded on the scaffold. We found that the combined stimulation of cyclic stretch and transforming growth factor beta 1 (TGF-β1) treatment not only increased cell viability but also synergistically promoted the differentiation of BMSCs into tenocytes in a 3D culture environment. Meanwhile, the combined stimulation increased the Young’s modulus of the BMSC-collagen sponge constructs by reducing the porosity of the scaffold compared to the non-treated constructs. Furthermore, a rat Achilles tendon in situ repair experiment showed that enhanced tendon regeneration was achieved using the BMSC-collagen sponge construct combined with cyclic stretch and TGF-β1, as confirmed by Achilles functional index (AFI) measurement, morphological observation, histological analysis, and mechanical testing. These results suggest that this approach could offer a practical benefit in tendon healing and future tendon tissue engineering. Statement of Significance This study aims to disclose the crucial roles of the coupled induction by mechano-chemical stimulation in tendon tissue engineering and clarifies their collaborative control mechanisms. We developed a three-dimensional (3D) culture system based on a silicone chamber and collagen sponge scaffold that could deliver cyclic mechanical stretch and biochemical stimulation to bone marrow-derived mesenchymal stem cells (BMSCs). We found that the combined stimulation of cyclic stretch and transforming growth factor beta 1 (TGF-β1) could result in an improvement of tissue-engineered construct for enhancing tendon healing. These results suggest that this approach could offer a practical benefit in tendon healing and future tendon tissue engineering.