Bone Morphogenetic Protein-9 Promotes Osteogenic Differentiation and Mineralization in Human Stem-Cell-Derived Spheroids.

Background and Objectives: Alkaline phosphatase activity, mineralized matrix, and osteogenic-related gene expression have been shown to increase in response to bone morphogenetic protein-9 (BMP-9). In this study, spheroids derived from human gingival stem cells were used to determine the effects of BMP-9 on cell survival, osteogenesis, and mineralization. Materials and Methods: Human gingival stem cells were used to produce spheroids and then grown to concentrations of 0, 0.1, 1, 10, and 100 ng/mL with BMP-9. On days 1, 3, 5, and 7, morphological examination was carried out. A live/dead assay and Cell Counting Kit-8 was used to assess the vitality of cells. On days 7 and 14, alkaline phosphatase activity assays were carried out using a commercially available kit to examine the osteogenic differentiation of cell spheroids. Alizarin Red Staining was performed on the 7th and 14th days to evaluate mineralization, and RUNX2 and COL1A1 expression levels were evaluated on the 7th and 14th days using real-time polymerase chain reactions. Results: The BMP-9 added at the measured quantities did not appear to alter the shape of the well-formed spheroids produced by stem cells on day 1. In addition, treatment with BMP-9 at doses of 0, 0.1, 1, 10, or 100 ng/mL did not significantly alter cell diameter. Throughout the whole experimental process, viability was maintained. On day 14, the alkaline phosphatase activity in the groups dosed with 0.1, 1, 10, or 100 ng/mL was statistically higher than that in the unloaded control group (p < 0.05). According to qPCR data, the mRNA expression level of RUNX2 with 1 ng/mL dosing was higher on day 7 compared to that of the unloaded control group (p < 0.05). Conclusions: These findings suggest that BMP-9 can be employed to stimulate early osteogenic differentiation in stem cell spheroids.

Phage Cocktail in Combination with Kasugamycin as a Potential Treatment for Fire Blight Caused by Erwinia amylovora.

Recently, there has been an increasing number of blight disease reports associated with Erwinia amylovora and Erwinia pyrifoliae in South Korea. Current management protocols that have been conducted with antibiotics have faced resistance problems and the outbreak has not decreased. Because of this concern, the present study aimed to provide an alternative method to control the invasive fire blight outbreak in the nation using bacteriophages (phages) in combination with an antibiotic agent (kasugamycin). Among 54 phage isolates, we selected five phages, pEa_SNUABM_27, 31, 32, 47, and 48, based on their bacteriolytic efficacy. Although only phage pEa_SNUABM_27 showed host specificity for E. amylovora, all five phages presented complementary lytic potential that improved the host infectivity coverage of each phage All the phages in the cocktail solution could lyse phage-resistant strains. These strains had a decreased tolerance to the antibiotic kasugamycin, and a synergistic effect of phages and antibiotics was demonstrated both in vitro and on immature wound-infected apples. It is noteworthy that the antibacterial effect of the phage cocktail or phage cocktail-sub-minimal inhibitory concentration (MIC) of kasugamycin was significantly higher than the kasugamycin at the MIC. The selected phages were experimentally stable under environmental factors such as thermal or pH stress. Genomic analysis revealed these are novel Erwinia-infecting phages, and did not encode antibiotic-, virulence-, or lysogenic phage-related genes. In conclusion, we suggest the potential of the phage cocktail and kasugamycin combination as an effective strategy that would minimize the use of antibiotics, which are being excessively used in order to control fire blight pathogens.

Synthesis of N-substituted quaternary carbon centers through KOt-Bu-catalyzed aza-Michael addition of pyrazoles to cyclic enones.

This study reports an efficient and mild method for the synthesis of cyclic ß-amino ketones containing N-substituted quaternary carbon centers via the KOt-Bu-catalyzed aza-Michael addition reaction of pyrazoles to ß-substituted cyclic α,ß-enones. The amination was promoted by KOt-Bu (3 mol%) at ambient temperature and a wide range of new and versatile ß-pyrazolyl ketones were obtained in good yields. Furthermore, the KOt-Bu-catalyzed one-pot diamination of a cyclic dienone with pyrazoles via an aza-1,6-conjugate addition followed by an aza-1,4-conjugate addition was also explored.

Prolongation of Fate of Bacteriophages In Vivo by Polylactic-Co-Glycolic-Acid/Alginate-Composite Encapsulation.

With concern growing over antibiotics resistance, the use of bacteriophages to combat resistant bacteria has been suggested as an alternative strategy with which to enable the selective control of targeted pathogens. One major challenge that restrains the therapeutic application of bacteriophages as antibacterial agents is their short lifespan, which limits their antibacterial effect in vivo. Here, we developed a polylactic-co-glycolic acid (PLGA)/alginate-composite microsphere for increasing the lifespan of bacteriophages in vivo. The alginate matrix in PLGA microspheres encapsulated the bacteriophages and protected them against destabilization by an organic solvent. Encapsulated bacteriophages were detected in the tissue for 28 days post-administration, while the bacteriophages administered without advanced encapsulation survived in vivo for only 3-5 days. The bacteriophages with extended fate showed prophylaxis against the bacterial pathogens for 28 days post-administration. This enhanced prophylaxis is presumed to have originated from the diminished immune response against these encapsulated bacteriophages because of their controlled release. Collectively, composite encapsulation has prophylactic potential against bacterial pathogens that threaten food safety and public health.

Higher-Order Topological Insulator in Twisted Bilayer Graphene.

Higher-order topological insulators are newly proposed topological phases of matter, whose bulk topology manifests as localized modes at two- or higher-dimensional lower boundaries. In this Letter, we propose the twisted bilayer graphenes with large angles as higher-order topological insulators, hosting topological corner charges. At large commensurate angles, the intervalley scattering opens up the bulk gap and the corner states occur at half filling. Based on both first-principles calculations and analytic analysis, we show the striking results that the emergence of the corner states do not depend on the choice of the specific angles as long as the underlying symmetries are intact. Our results show that the twisted bilayer graphene can serve as a robust candidate material of a two-dimensional higher-order topological insulator.

Unveiling hidden multipolar orders with magnetostriction.

Broken symmetries in solids involving higher order multipolar degrees of freedom are historically referred to as "hidden orders" due to the formidable task of detecting them with conventional probes. In this work, we theoretically propose that magnetostriction provides a powerful and novel tool to directly detect higher-order multipolar symmetry breaking-such as the elusive octupolar order-by examining scaling behaviour of length change with respect to an applied magnetic field h. Employing a symmetry-based Landau theory, we focus on the family of Pr-based cage compounds with strongly correlated f-electrons, Pr(Ti,V,Ir)2(Al,Zn)20, whose low energy degrees of freedom are purely higher-order multipoles: quadrupoles [Formula: see text] and octupole [Formula: see text]. We demonstrate that a magnetic field along the [111] direction induces a distinct linear-in-h length change below the octupolar ordering temperature. The resulting "magnetostriction coefficient" is directly proportional to the octupolar order parameter, thus providing clear access to such subtle order parameters.

Magnetic Chern Insulators in a monolayer of Transition Metal Trichalcogenides.

A monolayer of transition metal trichalcogenides has received a lot of attention as potential two dimensional magnetic materials. The system has a honeycomb structure of transition metal ions, where both spin-orbit coupling and electron correlation effect play an important role. Here, motivated by these transition metal series with effective doping or mixed valence case, we propose the possible realization of magnetic Chern insulators at quarter filled honeycomb lattice. We show that the interplay of intrinsic spin-orbit coupling and electron correlation opens a wide region of ferromagnetic Chern insulating phases in between metals and normal insulators. Within the mean field approximation, we present the phase diagram of a quarter filled Kane-Mele Hubbard model and also discuss the effects of Rashba spin-orbit coupling and nearest neighbor interactions on it.

Switching Magnetism and Superconductivity with Spin-Polarized Current in Iron-Based Superconductor.

We explore a new mechanism for switching magnetism and superconductivity in a magnetically frustrated iron-based superconductor using spin-polarized scanning tunneling microscopy (SPSTM). Our SPSTM study on single-crystal Sr_{2}VO_{3}FeAs shows that a spin-polarized tunneling current can switch the Fe-layer magnetism into a nontrivial C_{4} (2×2) order, which cannot be achieved by thermal excitation with an unpolarized current. Our tunneling spectroscopy study shows that the induced C_{4} (2×2) order has characteristics of plaquette antiferromagnetic order in the Fe layer and strongly suppresses superconductivity. Also, thermal agitation beyond the bulk Fe spin ordering temperature erases the C_{4} state. These results suggest a new possibility of switching local superconductivity by changing the symmetry of magnetic order with spin-polarized and unpolarized tunneling currents in iron-based superconductors.

RKKY interactions and the anomalous Hall effect in metallic rare-earth pyrochlores.

Motivated by experiments on Pr2Ir2O7, we consider metallic pyrochlore systems A2B2O7, where the A sites are occupied by rare-earth local moments and the B sites host 5d transition metal ions with itinerant strongly spin-orbit coupled electrons. Assuming non-Kramers doublets on the A site, we derive the RKKY interaction between them mediated by the B-site itinerant electrons and find extended non-Heisenberg interactions. Analyzing a simplified model of the RKKY interaction, we uncover a local moment phase with coexisting spiral Ising-like magnetic dipolar and XY-like quadrupolar ordering. This state breaks time-reversal and lattice symmetries, and reconstructs the B-site electronic band structure, producing a Weyl metallic phase with an intrinsic anomalous Hall effect and an undetectably small magnetization. We discuss implications of our results for Pr2Ir2O7.

Landau theory of charge and spin ordering in the nickelates.

Guided by experiment and band structure, we introduce and study a phenomenological Landau theory for the unusual charge and spin ordering associated with the Mott transition in the perovskite nickelates, with chemical formula RNiO3, where R=Pr, Nd,Sm, Eu, Ho, Y, and Lu. While the Landau theory has general applicability, we show that for the most conducting materials, R=Pr, Nd, both types of order can be understood in terms of a nearly nested spin-density wave. Furthermore, we argue that in this regime, the charge ordering is reliant upon the orthorhombic symmetry of the sample, and therefore proportional to the magnitude of the orthorhombic distortion. The first order nature of the phase transitions is also explained. We briefly show by example how the theory is readily adapted to modified geometries such as nickelate films.