Anisotropic Electron Mobility and Contact Resistance of ß-Ga2O3 Obtained via Radio Frequency Transmission Line Methods on Schottky Devices.

Monoclinic semiconducting ß-Ga2O3 has drawn attention, particularly because its thin film could be achieved via mechanical exfoliation from bulk crystals, which is analogous to van der Waals materials' behavior. For the transistor devices with exfoliated ß-Ga2O3, the channel direction becomes [010] for in-plane electron transport, which changes to vertical [100] near the source/drain (S/D) contact. Hence, anisotropic transport behavior is certainly worth to study but rarely reported. Here we achieve the vertical [100] direction electron mobility of 4.18 cm2/(V s) from Pt/ß-Ga2O3 Schottky diodes with various thickness via radio frequency-transmission line method (RF-TLM), which is recently developed. The specific contact resistivity (ρc) could also be estimated from RF-TLM, to be 4.72 × 10-5 Ω cm2, which is quite similar to the value (5.25 × 10-5 Ω cm2) from conventional TLM proving the validity of RF-TLM. We also fabricate metal-semiconductor field-effect transistors (MESFETs) to study anisotropic transport behavior and contact resistance (RC). RC-free [010] in-plane mobility appears as high as maximum ∼67 cm2/(V s), extracted from total resistance in MESFETs.

5 nm Ultrathin Crystalline Ferroelectric P(VDF-TrFE)-Brush Tuned for Hysteresis-Free Sub 60 mV dec-1 Negative-Capacitance Transistors.

Negative-capacitance field-effect transistors (NC-FETs) have gathered enormous interest as a way to reduce subthreshold swing (SS) and overcome the issue of power dissipation in modern integrated circuits. For stable NC behavior at low operating voltages, the development of ultrathin ferroelectrics (FE), which are compatible with the industrial process, is of great interest. Here, a new scalable ultrathin ferroelectric polymer layer is developed based on trichloromethyl (CCl3 )-terminated poly(vinylidene difluoride-co-trifloroethylene) (P(VDF-TrFE)) to achieve the state-of-the-art performance of NC-FETs. The crystalline phase of 5-10 nm ultrathin P(VDF-TrFE) is prepared on AlOX by a newly developed brush method, which enables an FE/dielectric (DE) bilayer. FE/DE thickness ratios are then systematically tuned at ease to achieve ideal capacitance matching. NC-FETs with optimized FE/DE thickness at a thickness limit demonstrate hysteresis-free operation with an SS of 28 mV dec-1 at ≈1.5 V, which competes with the best reports. This P(VDF-TrFE)-brush layer can be broadly adapted to NC-FETs, opening an exciting avenue for low-power devices.

PTX-3 Secreted by Intra-Articular-Injected SMUP-Cells Reduces Pain in an Osteoarthritis Rat Model.

Mesenchymal stem cells (MSCs) are accessible, abundantly available, and capable of regenerating; they have the potential to be developed as therapeutic agents for diseases. However, concerns remain in their further application. In this study, we developed a SMall cell+Ultra Potent+Scale UP cell (SMUP-Cell) platform to improve whole-cell processing, including manufacturing bioreactors and xeno-free solutions for commercialization. To confirm the superiority of SMUP-Cell improvements, we demonstrated that a molecule secreted by SMUP-Cells is capable of polarizing inflammatory macrophages (M1) into their anti-inflammatory phenotype (M2) at the site of injury in a pain-associated osteoarthritis (OA) model. Lipopolysaccharide-stimulated macrophages co-cultured with SMUP-Cells expressed low levels of M1-phenotype markers (CD11b, tumor necrosis factor-α, interleukin-1α, and interleukin-6), but high levels of M2 markers (CD163 and arginase-1). To identify the paracrine action underlying the anti-inflammatory effect of SMUP-Cells, we employed a cytokine array and detected increased levels of pentraxin-related protein-3 (PTX-3). Additionally, PTX-3 mRNA silencing was applied to confirm PTX-3 function. PTX-3 silencing in SMUP-Cells significantly decreased their therapeutic effects against monosodium iodoacetate (MIA)-induced OA. Thus, PTX-3 expression in injected SMUP-Cells, applied as a therapeutic strategy, reduced pain in an OA model.

Ambipolar Channel p-TMD/n-Ga2 O3 Junction Field Effect Transistors and High Speed Photo-sensing in TMD Channel.

Highly crystalline 2D/3D-mixed p-transition metal dichalcogenide (TMD)/n-Ga2 O3 heterojunction devices are fabricated by mechanical exfoliation of each p- and n-type material. N-type ß-Ga2 O3 and p-type TMD separately play as a channel for junction field effect transistors (JFETs) with each type of carriers as well as materials for a heterojunction PN diode. The work thus mainly focuses on such ambipolar channel transistors with two different types of channel in a single device architecture. For more extended applications, the transparency of high energy band gap ß-Ga2 O3 (Eg  ≈ 4.8 eV) is taken advantage of, firstly to measure the electrical energy gap of p-TMDs receiving visible or near infrared (NIR) photons through the ß-Ga2 O3 . Next, the p-TMD/n-Ga2 O3 JFETs are put to high speed photo-sensing which is achieved from the p-TMD channel under reverse bias voltages on n-Ga2 O3 . The photo-switching cutoff frequency appears to be ≈16 and 29 kHz for visible red and NIR illuminations, respectively, on the basis of -3 dB photoelectric power loss. Such a high switching speed of the JFET is attributed to the fast transport of photo-carriers in TMD channels. The 2D/3D-mixed ambipolar channel JFETs and their photo-sensing applications are regarded novel, promising, and practically easy to achieve.

A neurovascular-unit-on-a-chip for the evaluation of the restorative potential of stem cell therapies for ischaemic stroke.

The therapeutic efficacy of stem cells transplanted into an ischaemic brain depends primarily on the responses of the neurovascular unit. Here, we report the development and applicability of a functional neurovascular unit on a microfluidic chip as a microphysiological model of ischaemic stroke that recapitulates the function of the blood-brain barrier as well as interactions between therapeutic stem cells and host cells (human brain microvascular endothelial cells, pericytes, astrocytes, microglia and neurons). We used the model to track the infiltration of a number of candidate stem cells and to characterize the expression levels of genes associated with post-stroke pathologies. We observed that each type of stem cell showed unique neurorestorative effects, primarily by supporting endogenous recovery rather than through direct cell replacement, and that the recovery of synaptic activities is correlated with the recovery of the structural and functional integrity of the neurovascular unit rather than with the regeneration of neurons.

Positively Correlated CD47 Activation and Autophagy in Umbilical Cord Blood-Derived Mesenchymal Stem Cells during Senescence.

Autophagy plays a critical role in stem cell maintenance and is related to cell growth and cellular senescence. It is important to find a quality-control marker for predicting senescent cells. This study verified that CD47 could be a candidate to select efficient mesenchymal stem cells (MSCs) to enhance the therapeutic effects of stem cell therapy by analyzing the antibody surface array. CD47 expression was significantly decreased during the expansion of MSCs in vitro (p < 0.01), with decreased CD47 expression correlated with accelerated senescence phenotype, which affected cell growth. UCB-MSCs transfected with CD47 siRNA significantly triggered the downregulation of pRB and upregulation of pp38, which are senescence-related markers. Additionally, autophagy-related markers, ATG5, ATG12, Beclin1, and LC3B, revealed significant downregulation with CD47 siRNA transfection. Furthermore, autophagy flux following treatment with an autophagy inducer, rapamycin, has shown that CD47 is a key player in autophagy and senescence to maintain and regulate the growth of MSCs, suggesting that CD47 may be a critical key marker for the selection of effective stem cells in cell therapy.

Reduced extrinsic recombination process in anatase and rutile TiO2 epitaxial thin films for efficient electron transport layers.

TiO2 is the most widely used material for the electron transport layers (ETLs) because it is characterized by proper band alignment with light absorbers, adequate optical transmittance, and high electron mobility. There are two thermodynamically stable crystal phases of TiO2: anatase and rutile. However, understanding which phase is more effective as the ETL is still required. In this paper, we demonstrate the different effects of using epitaxial anatase TiO2 and epitaxial rutile TiO2 (both grown using pulsed laser deposition) as the ETL material on the electrical and optical properties. Epitaxial Nb-doped TiO2 layers were used as the common electrode material for the both epitaxial ETLs for which the crystalline structural analysis revealed high crystalline qualities and good coherency for both phases. By analyzing the recombination kinetics, the anatase phase shows a preferable performance in comparison with the rutile phase, although both epitaxial phases show remarkably reduced extrinsic recombination properties, such as trap-assisted recombination. This study demonstrates not only a better electron transporting performance of anatase phase but also reduced extrinsic recombination through epitaxy growth.

Senescence-Associated Secretory Phenotype Suppression Mediated by Small-Sized Mesenchymal Stem Cells Delays Cellular Senescence through TLR2 and TLR5 Signaling.

In order to provide a sufficient number of cells for clinical use, mesenchymal stem cells (MSCs) must be cultured for long-term expansion, which inevitably triggers cellular senescence. Although the small size of MSCs is known as a critical determinant of their fate, the main regulators of stem cell senescence and the underlying signaling have not been addressed. Umbilical cord blood-derived MSCs (UCB-MSCs) were obtained using size-isolation methods and then cultured with control or small cells to investigate the major factors that modulate MSC senescence. Cytokine array data suggested that the secretion of interukin-8 (IL-8) or growth-regulated oncogene-alpha (GROa) by senescent cells was markedly inhibited during incubation of small cells along with suppression of cognate receptor (C-X-C motif chemokine receptor2, CXCR2) via blockade of the autocrine/paracrine positive loop. Moreover, signaling via toll-like receptor 2 (TLR2) and TLR5, both pattern recognition receptors, drove cellular senescence of MSCs, but was inhibited in small cells. The activation of TLRs (2 and 5) through ligand treatment induced a senescent phenotype in small cells. Collectively, our data suggest that small cell from UCB-MSCs exhibit delayed cellular senescence by inhibiting the process of TLR signaling-mediated senescence-associated secretory phenotype (SASP) activation.

High Integrity and Fidelity of Long-Term Cryopreserved Umbilical Cord Blood for Transplantation.

Umbilical cord blood (UCB) is used as a source of donor cells for hematopoietic stem cell (HSC) transplantation. The success of transplantation is dependent on the quality of cord blood (CB) units for maximizing the chance of engraftment. Improved outcomes following transplantation are associated with certain factors of cryopreserved CB units: total volume and total nucleated cell (TNC) count, mononuclear cell (MNC) count, and CD34+ cell count. The role of the storage period of CB units in determining the viability and counts of cells is less clear and is related to the quality of cryopreserved CB units. Herein, we demonstrate the recovery of viable TNCs and CD34+ cells, as well as the MNC viability in 20-year-old cryopreserved CB units in a CB bank (MEDIPOST Co., Ltd., Seongnam-si, Gyeonggi-do, Korea). In addition, cell populations in CB units were evaluated for future clinical applications. The stable recovery rate of the viability of cryopreserved CB that had been stored for up to 20 years suggested the possibility of uses of the long-term cryopreservation of CB units. Similar relationships were observed in the recovery of TNCs and CD34+ cells in units of cryopreserved and fresh CB. The high-viability recovery of long-term cryopreserved CB suggests that successful hematopoietic stem cell (HSC) transplantation and other clinical applications, which are suitable for treating incurable diseases, may be performed regardless of long-term storage.

CD26 Inhibition Potentiates the Therapeutic Effects of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells by Delaying Cellular Senescence.

Mesenchymal stem cells (MSCs) are recognized as potential treatments for multiple degenerative and inflammatory disorders as a number of animal and human studies have indicated their therapeutic effects. There are also several clinically approved medicinal products that are manufactured using these cells. For such large-scale manufacturing requirements, the in vitro expansion of harvested MSCs is essential. Multiple subculturing of MSCs, however, provokes cellular senescence processes which is known to deteriorate the therapeutic efficacy of the cells. Strategies to rejuvenate or selectively remove senescent MSCs are therefore highly desirable for fostering future clinical applications of these cells. In this present study, we investigated gene expression changes related to cellular senescence of MSCs derived from umbilical cord blood and found that CD26, also known as DPP4, is significantly upregulated upon cellular aging. We further observed that the inhibition of CD26 by genetic or pharmacologic means delayed the cellular aging of MSCs with their multiple passaging in culture. Moreover, the sorting and exclusion of CD26-positive MSCs from heterogenous cell population enhanced in vitro cell attachment and reduced senescence-associated cytokine secretion. CD26-negative MSCs also showed superior therapeutic efficacy in mouse lung emphysema model. Our present results collectively suggest CD26 is a potential novel target for the rejuvenation of senescent MSCs for their use in manufacturing MSC-based applications.