Experimental Observation and Spin Texture of Dirac Node Arcs in Tetradymite Topological Metals.

We report the observation of a nontrivial spin texture in Dirac node arcs, i.e., novel topological objects formed when Dirac cones of massless particles extend along an open one-dimensional line in momentum space. We find that such states are present in all the compounds of the tetradymite M_{2}Te_{2}X family (M=Ti, Zr, or Hf and X=P or As) regardless of the weak or strong character of the topological invariant. The Dirac node arcs in tetradymites are thus the simplest possible textbook example of a type-I Dirac system with a single spin-polarized node arc.

NF-kB decoy oligodeoxynucleotide preserves disc height in a rabbit anular-puncture model and reduces pain induction in a rat xenograft-radiculopathy model.

While it is known that the degenerated intervertebral disc (IVD) is one of the primary reasons for low-back pain and subsequent need for medical care, there are currently no established effective methods for direct treatment. Nuclear factor-κB (NF-κB) is a transcription factor that regulates various genes' expression, among which are inflammatory cytokines, in many tissues including the IVD. NF-κB decoy is an oligodeoxynucleotide containing the NF-κB binding site that entraps NF-κB subunits, resulting in suppression of NF-κB activity. In the present preclinical study, NF-κB decoy was injected into degenerated IVDs using the rabbit anular-puncture model. In terms of distribution, NF-κB decoy persisted in the IVDs up to at least 4 weeks after injection. The remaining amount of NF-κB decoy indicated that it fit a double-exponential-decay equation. Investigation of puncture-caused degeneration of IVDs showed that NF-κB decoy injection recovered, dose-dependently, the reduced disc height that was associated with reparative cell cloning and morphological changes, as assessed through histology. Gene expression, by quantitative real-time polymerase chain reaction (qRT-PCR), showed that NF-κB decoy attenuated inflammatory gene expression, such as that of interleukin-1 and tumor necrosis factor-α, in rabbit degenerated IVDs. NF-κB decoy also reduced the pain response as seen using the "pain sensor" nude rat xenograft-radiculopathy model. This is the first report demonstrating that NF-κB decoy suppresses the inflammatory response in degenerated IVDs and restores IVD disc height loss. Therefore, the intradiscal injection of NF-κB decoy may have the potential as an effective therapeutic strategy for discogenic pain associated with degenerated IVDs.

Radial Spin Texture in Elemental Tellurium with Chiral Crystal Structure.

The chiral crystal is characterized by a lack of mirror symmetry and inversion center, resulting in the inequivalent right- and left-handed structures. In the noncentrosymmetric crystal structure, the spin and momentum of electrons are expected to be locked in the reciprocal space with the help of the spin-orbit interaction. To reveal the spin textures of chiral crystals, we investigate the spin and electronic structure in a p-type semiconductor, elemental tellurium, with the simplest chiral structure by using spin- and angle-resolved photoemission spectroscopy. Our data demonstrate that the highest valence band crossing the Fermi level has a spin component parallel to the electron momentum around the Brillouin zone corners. Significantly, we have also confirmed that the spin polarization is reversed in the crystal with the opposite chirality. The results indicate that the spin textures of the right- and left-handed chiral crystals are hedgehoglike, leading to unconventional magnetoelectric effects and nonreciprocal phenomena.

Cubic Rashba Effect in the Surface Spin Structure of Rare-Earth Ternary Materials.

Spin-orbit interaction and structure inversion asymmetry in combination with magnetic ordering is a promising route to novel materials with highly mobile spin-polarized carriers at the surface. Spin-resolved measurements of the photoemission current from the Si-terminated surface of the antiferromagnet TbRh_{2}Si_{2} and their analysis within an ab initio one-step theory unveil an unusual triple winding of the electron spin along the fourfold-symmetric constant energy contours of the surface states. A two-band k·p model is presented that yields the triple winding as a cubic Rashba effect. The curious in-plane spin-momentum locking is remarkably robust and remains intact across a paramagnetic-antiferromagnetic transition in spite of spin-orbit interaction on Rh atoms being considerably weaker than the out-of-plane exchange field due to the Tb 4f moments.

Tumour-suppressive miRNA-26a-5p and miR-26b-5p inhibit cell aggressiveness by regulating PLOD2 in bladder cancer.

BACKGROUND: Previous studies have revealed that miR-26a-5p and miR-26b-5p act as tumour suppressors in various types of cancer tissues. Here, we aimed to investigate the functional roles of these miRNAs and to identify their regulatory targets in bladder cancer (BC). METHODS: We performed functional assays in BC cells using transfection of mature microRNAs (miRNAs). In silico and luciferase reporter analyses were applied to identify target genes of these miRNAs. The overall survival (OS) of patients with BC was evaluated by the Kaplan-Meier method. RESULTS: miR-26a-5p and miR-26b-5p were significantly downregulated in BC tissues. Restoration of these miRNAs inhibited cell migration and invasion in BC. The gene encoding procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), a collagen crosslinking enzyme, was directly regulated by miR-26a-5p and miR-26b-5p. Kaplan-Meier analysis revealed that patients with high PLOD2 expression had significantly shorter OS compared with those with low PLOD2 expression (P=0.0153). CONCLUSIONS: PLOD2, which is associated with the stiffness of the extracellular matrix, was directly regulated by miR-26a-5p and miR-26b-5p and may be a good prognostic marker in patients with BC.

Pharmacological effects of novel cross-linked hyaluronate, Gel-200, in experimental animal models of osteoarthritis and human cell lines.

OBJECTIVE: To study the pharmacological effects of Gel-200, cross-linked hyaluronate. EXPERIMENTAL DESIGN: We examined the chondroprotective, anti-inflammatory and analgesic effects of Gel-200 in experimental animal models for osteoarthritis (OA) and in a human synovial sarcoma cell line and normal human articular chondrocytes. RESULTS: In the OA model, a single-dose intra-articular (IA) injection of Gel-200 significantly suppressed cartilage degeneration and reduced synovitis of the knee joint. In the joint pain model, Gel-200 significantly suppressed pain responses for 4 weeks after injection. The residual property of Gel-200 in the knee joint tissue was investigated in rabbits. The mean residual ratio of injected Gel-200 in the synovium was 3.3% (95% confidence interval [CI], 2.4-4.2) at 28 days after the injection. The long-lasting analgesic effect of Gel-200 might be explained by its high residual ratio in the joint. In addition, we investigated the mechanism of action of Gel-200 in a human synovial sarcoma cell line and normal human articular chondrocytes. Gel-200 inhibited IL-1ß-induced production of MMP-1, 3 and 13 in human chondrocytes and production of prostaglandin E2 in human synoviocytes in a concentration-dependent manner, respectively. CONCLUSION: A single-dose IA injection of Gel-200 exerts chondroprotective and anti-inflammatory effects in the experimental OA model, and long-lasting analgesia in the joint pain model, suggesting the beneficial multimodal function of Gel-200 against symptomatic OA patients.

Photoelectron spin-polarization control in the topological insulator Bi2Se3.

We study the manipulation of the spin polarization of photoemitted electrons in Bi2Se3 by spin- and angle-resolved photoemission spectroscopy. General rules are established that enable controlling the photoelectron spin-polarization. We demonstrate the ± 100% reversal of a single component of the measured spin-polarization vector upon the rotation of light polarization, as well as full three-dimensional manipulation by varying experimental configuration and photon energy. While a material-specific density-functional theory analysis is needed for the quantitative description, a minimal yet fully generalized two-atomic-layer model qualitatively accounts for the spin response based on the interplay of optical selection rules, photoelectron interference, and topological surface-state complex structure. It follows that photoelectron spin-polarization control is generically achievable in systems with a layer-dependent, entangled spin-orbital texture.

Seasonal changes in gene expression of corticoid receptors in anadromous and non-anadromous strains of rainbow trout Oncorhynchus mykiss.

To clarify the regulation of expression of corticoid receptor (CR) genes during period of parr-smolt transformation of salmonids, seasonal changes in mRNA levels of glucocorticoid receptor (GR)-1, GR-2 and mineralocorticoid receptor (MR) were examined in gill, leucocytes, spleen and brain of anadromous and non-anadromous forms of Oncorhynchus mykiss. Increases in gill Na(+) , K(+) ATPase activity, plasma thyroxine levels and hypo-osmoregulatory ability assessed by 24 h seawater challenge test represented characteristics of smoltification in anadromous O. mykiss from May to June, whereas there was no apparent increase in the values of non-anadromous O. mykiss. Plasma cortisol levels of anadromous O. mykiss were higher than levels of non-anadromous O. mykiss from April to June. In gill of non-anadromous O. mykiss, there were significant increases in mRNA levels of three types of CR in spring. Although there were significant seasonal variations of CR mRNA levels in gill of anadromous O. mykiss, they appear to be less clear than those variations in non-anadromous O. mykiss. In anadromous O. mykiss, significant elevations in mRNA levels of the three types of CR were observed especially in the spleen. In both preoptic area and basal hypothalamus of the brain, there were tendencies to increase in CR mRNA levels from spring to summer in both anadromous and non-anadromous O. mykiss. These results showed difference in regulation of CR gene expression between the two forms of O. mykiss for osmoregulatory, immune and central nervous systems.

Laser-based angle-resolved photoemission spectroscopy with micrometer spatial resolution and detection of three-dimensional spin vector.

We have developed a state-of-the-art apparatus for laser-based spin- and angle-resolved photoemission spectroscopy with micrometer spatial resolution (µ-SARPES). This equipment is realized by the combination of a high-resolution photoelectron spectrometer, a 6 eV laser with high photon flux that is focused down to a few micrometers, a high-precision sample stage control system, and a double very-low-energy-electron-diffraction spin detector. The setup achieves an energy resolution of 1.5 (5.5) meV without (with) the spin detection mode, compatible with a spatial resolution better than 10 µm. This enables us to probe both spatially-resolved electronic structures and vector information of spin polarization in three dimensions. The performance of µ-SARPES apparatus is demonstrated by presenting ARPES and SARPES results from topological insulators and Au photolithography patterns on a Si (001) substrate.

Integrin α3 is overexpressed in glioma stem-like cells and promotes invasion.

BACKGROUND: Glioma stem-like cell (GSC) properties are responsible for gliomagenesis and recurrence. GSCs are invasive but its mechanism remains to be elucidated. Here, we attempted to identify the molecules that promote invasion in GSCs. METHODS: Neurospheres and CD133⁺ cells were collected from glioblastoma (GBM) specimens and glioma cell lines by sphere-formation method and magnetic affinity cell sorting, respectively. Differential expression of gene candidates, its role in invasion and its signaling pathway were evaluated in glioma cell lines. RESULTS: Neurospheres from surgical specimens attached to fibronectin and laminin, the receptors of which belong to the integrin family. Integrin α3 was overexpressed in CD133⁺ cells compared with CD133⁻ cells in all the glioma cell lines (4 out of 4). Immunohistochemistry demonstrated the localisation of integrin α3 in GBM cells, including invading cells, and in the tumour cells around the vessels, which is believed to be a stem cell niche. The expression of integrin α3 was correlated with migration and invasion. The invasion activity of glioma cells was linked to the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. CONCLUSION: Our results suggest that integrin α3 contributes to the invasive nature of GSCs via ERK1/2, which renders integrin α3 a prime candidate for anti-invasion therapy for GBM.

Quantification and visualization of cellular NAD(P)H in young and aged female facial skin with in vivo two-photon tomography.

BACKGROUND: In vivo two-photon tomography is a novel noninvasive three-dimensional optical skin imaging technology with subcellular resolution which enables the sensitive detection of endogenous fluorophores. One of these fluorophores, NAD(P)H (a coenzyme which plays an important role in the release of free energy during glycolysis, and influences filaggrin and lipid synthesis), can be selectively detected in keratinocytes (granular cells) with two-photon tomography. OBJECTIVES: To quantify NAD(P)H levels in subsurface human facial skin in vivo as a measure to determine if there are changes with age. METHODS: A total of 80 healthy Asian females were enrolled in this study, aged 21-68 years. Measurements were performed on facial skin using in vivo two-photon tomography (DermaInspect/MPTflex™, JenLab GmbH, Jena, Germany). The laser beam scans a skin field of interest in pulses, focused at a depth to reach the granular layer. The near-infrared laser pulses excite the endogenous fluorophores NAD(P)H. Image processing was performed to obtain high-resolution autofluorescence images (optical biopsies) and to quantify the fluorescent grey scale to determine NAD(P)H levels. Additional skin surface measures taken were hydration (corneometer), elasticity (cutometer) and wrinkles (image capture and analysis). RESULTS: Statistically significant changes in all measured parameters as a function of age were observed. Most importantly, the mean fluorescent grey scale values for NAD(P)H in the youngest group studied (women in their 20s) was 38.8 (SD ± 12.39), while that of the oldest group studied (women in their 60s) was 32.7 (SD ± 12.47). These NAD(P)H levels are statistically significantly different (P = 0.0078). CONCLUSIONS: The level of NAD(P)H in the epidermis is significantly greater in younger vs. older skin in vivo. This likely reflects decreased production and/or increased degradation of NAD(P)H in older skin, possibly as a result of chronological ageing and environmental damage (e.g. photodamage). NAD(P)H levels in epidermal skin may be a useful biomarker of skin ageing in vivo. It is also likely that maintaining NAD(P)H production is a useful approach to maintaining good skin condition and caring for ageing skin.

Relationship between seasonal variation in isoprene emission and plant hormone profiles in the tropical plant Ficus septica.

In Ficus septica, the short-term control of isoprene production and, therefore, isoprene emission has been linked to the hormone balance between auxin (IAA) and jasmonic acid (JA). However, the relationship between long-term changes in isoprene emission and that of plant hormones remains unknown. This study tracked isoprene emissions from F. septica leaves, plant hormone concentrations and signalling gene expression, MEP pathway metabolite concentrations, and related enzyme gene expression for 1 year in the field to better understand the role of plant hormones and their long-term control. Seasonality of isoprenes was mainly driven by temperature- and light-dependent variations in substrate availability through the MEP route, as well as transcriptional and post-transcriptional control of isoprene synthase (IspS). Isoprene emissions are seasonally correlated with plant hormone levels. This was especially evident in the cytokinin profiles, which decreased in summer and increased in winter. Only 4-hydroxy-3-methylbut-2-butenyl-4-diphosphate (HMBDP) exhibited a positive connection with cytokinins among the MEP metabolites examined, suggesting that HMBDP and its biosynthetic enzyme, HMBDP synthase (HDS), play a role in channelling of MEP pathway metabolites to cytokinin production. Thus, it is probable that cytokinins have potential feed-forward regulation of isoprene production. Under long-term natural conditions, the hormonal balance of IAA/JA-Ile was not associated with IspS transcripts or isoprene emissions. This study builds on prior work by revealing differences between short- and long-term hormonal modulation of isoprene emissions in the tropical tree F. septica.

Giant Rashba-type spin splitting in bulk BiTeI.

There has been increasing interest in phenomena emerging from relativistic electrons in a solid, which have a potential impact on spintronics and magnetoelectrics. One example is the Rashba effect, which lifts the electron-spin degeneracy as a consequence of spin-orbit interaction under broken inversion symmetry. A high-energy-scale Rashba spin splitting is highly desirable for enhancing the coupling between electron spins and electricity relevant for spintronic functions. Here we describe the finding of a huge spin-orbit interaction effect in a polar semiconductor composed of heavy elements, BiTeI, where the bulk carriers are ruled by large Rashba-like spin splitting. The band splitting and its spin polarization obtained by spin- and angle-resolved photoemission spectroscopy are well in accord with relativistic first-principles calculations, confirming that the spin splitting is indeed derived from bulk atomic configurations. Together with the feasibility of carrier-doping control, the giant-Rashba semiconductor BiTeI possesses excellent potential for application to various spin-dependent electronic functions.

Spin-polarized Dirac-cone-like surface state with d character at W(110).

The surface of W(110) exhibits a Dirac-cone-like state with d character within a spin-orbit-induced symmetry gap. As a function of the wave vector parallel to the surface, it shows a nearly massless energy dispersion and a pronounced spin polarization, which is antisymmetric with respect to the Brillouin zone center. In addition, the observed constant energy contours are strongly anisotropic for all energies. This discovery opens new pathways to the study of surface spin-density waves arising from a strong Fermi surface nesting as well as d-electron-based topological properties.

Topological surface states with persistent high spin polarization across the Dirac point in Bi2Te2Se and Bi2Se2Te.

Helical spin textures with marked spin polarizations of topological surface states have been unveiled for the first time by state-of-the-art spin- and angle-resolved photoemission spectroscopy for two promising topological insulators, Bi(2)Te(2)Se and Bi(2)Se(2)Te. Their highly spin-polarized natures are found to be persistent across the Dirac point in both compounds. This novel finding paves a pathway to extending the utilization of topological surface states of these compounds for future spintronic applications.

Experimental verification of PbBi2Te4 as a 3D topological insulator.

The experimental evidence is presented of the topological insulator state in PbBi2Te4. A single surface Dirac cone is observed by angle-resolved photoemission spectroscopy with synchrotron radiation. Topological invariants Z2 are calculated from the ab initio band structure to be 1;(111). The observed two-dimensional isoenergy contours in the bulk energy gap are found to be the largest among the known three-dimensional topological insulators. This opens a pathway to achieving a sufficiently large spin current density in future spintronic devices.

Plant hormone profile and control over isoprene biosynthesis in a tropical tree Ficus septica.

Plant hormone signalling and the circadian clock have been implicated in the transcriptional control of isoprene biosynthesis. To gain more insight into the hormonal control of isoprene biosynthesis, the present study measured plant hormone concentrations in jasmonic acid (JA)-treated leaves of our previous model study, examined their relationship with gene expression of isoprene synthase (IspS) and hormone signalling transcription factors. Of the plant hormones, IAA and JA-Ile and their related transcription factors (MYC2 and SAUR21) were significantly correlated with IspS gene expression. Concentrations of cytokinins, isopentenyladenine (iP), trans-zeatin riboside (tZR) and cis-zeatin riboside (cZR), were similarly significantly correlated with IspS expression. However, there was no significant correlation between their related transcription factor (ARR-B) and IspS expression. The circadian clock-related gene PRR7, but not the transcription factor LHY, was highly correlated with IspS expression. These results suggest that the hormonal balance between JA-Ile and IAA plays a central role in transcriptional regulation of IspS through the transcription factors MYC2 and SAUR21, the early auxin responsive genes. The putative cis-acting elements for SAUR on the IspS promoter (TGTCNN and CATATG), in addition to the G-box for MYC2, support the above proposal. These results provide insightful information on the core components of plant hormone-related regulation of IspS under coordination with the circadian clock genes.

Association between the Mediterranean Diet Score and Healthy Life Expectancy: A Global Comparative Study.

OBJECTIVES: Extending healthy life expectancy (HALE), defined as the average number of years that a person can expect to live in "full health" by taking into account years lived in less than full health due to disease and/or injury, is a common topic worldwide. This study aims to clarify the relationships between the Mediterranean diet score (MDS) and life expectancy (LE) and HALE globally using publicly available international data. SETTING: Analyses were conducted on 130 countries with populations of 1 million or more for which all data were available. Individual countries were scored from 0 to 9 to indicate adherence to the Mediterranean diet according to the MDS scoring method. The supply of vegetables, legumes, fruits and nuts, cereals, fish, and olive oil per 1,000 kcal per country was calculated based on the Food and Agriculture Organization Corporate Statistical Database, with a score of 1 for above the median and 0 for below. The same method was used to calculate scores of presumed detrimental components (meat and dairy), with consumption below the median given a value of 1, and consumption above the median given a value of 0. For ethanol, a score of 1 was given for 10g to 50 g of consumption. We investigated the cross-sectional associations between the MDS and LE and HALE at birth in 2009, and the longitudinal associations between the MDS in 2009 and LE and HALE between 2009 and 2019, controlling for covariates at baseline using linear mixed models. RESULTS: In the cross-sectional analysis, the MDS was significantly positively associated with LE (ß=0.906 [95% confidence interval, 0.065-1.747], p=0.037) and HALE (ß=0.875 [0.207-1.544], p=0.011) after controlling for all covariates. The longitudinal analysis also revealed significantly positive associations between the MDS and LE (0.621 [0.063-1.178], p=0.030) and HALE (0.694 [0.227-1.161], p=0.004) after controlling for all covariates. CONCLUSION: The present study, based on an analysis using 10 years of international data, showed that countries with a higher MDS showed a positive association with HALE.

Engineered extracellular vesicles antagonize SARS-CoV-2 infection by inhibiting mTOR signaling.

Effective treatment approaches for patients with COVID-19 remain limited and are neither curative nor widely applicable. Activated specialized tissue effector extracellular vesicles (ASTEX) derived from genetically-enhanced skin fibroblasts, exert disease-modifying bioactivity in vivo in models of heart and lung injury. Here we report that ASTEX antagonizes SARS-CoV-2 infection and its pathogenic sequelae. In human lung epithelial cells exposed to SARS-CoV-2, ASTEX is cytoprotective and antiviral. Transcriptomic analysis implicated the mammalian target of rapamycin (mTOR) pathway, as infected cells upregulated mTOR signaling and pre-exposure to ASTEX attenuated it. The implication of mTOR signaling was further confirmed using mTOR inhibition and activation, which increased and decreased viral load, respectively. Dissection of ASTEX cargo identifies miRs including miR-16 as potential inhibitors of mTOR signaling. The findings reveal a novel, dual mechanism of action for ASTEX as a therapeutic candidate for COVID-19, with synergistic antiviral and cytoprotective benefits.

SNP-based analysis of the HLA locus in Japanese multiple sclerosis patients.

Although several major histocompatibility complex (MHC)-wide single-nucleotide polymorphism (SNP) studies have been performed in populations of European descent, none have been performed in Asian populations. The objective of this study was to identify human leukocyte antigen (HLA) loci associated with multiple sclerosis (MS) in a Japanese population genotyped for 3534 MHC region SNPs. Using a logistic regression model, two SNPs (MHC Class III SNP rs422951 in the NOTCH4 gene and MHC Class II SNP rs3997849, susceptible alleles A and G, respectively) were independently associated with MS susceptibility (204 patients; 280 controls), two (MHC Class II SNP rs660895 and MHC Class I SNP rs2269704 in the NRM gene, susceptible alleles G and G, respectively) with aquaporin-4- (AQP4-) MS susceptibility (149 patients; 280 controls) and a single SNP (MHC Class II SNP rs1694112, susceptible allele G) was significant when contrasting AQP4+ against AQP4- patients. Haplotype analysis revealed a large susceptible association, likely DRB1*04 or a locus included in the DRB1*04 haplotype, with AQP4- MS, which excluded DRB1*15:01. This study is the largest study of the HLA's contribution to MS in Japanese individuals.