Emergent Ferromagnetism in CaRuO3/CaMnO3 (111)-Oriented Superlattices.

The boundary between CaRuO3 and CaMnO3 is an ideal test bed for emergent magnetic ground states stabilized through interfacial electron interactions. In this system, nominally antiferromagnetic and paramagnetic materials combine to yield interfacial ferromagnetism in CaMnO3 due to electron leakage across the interface. In this work, we show that the crystal symmetry at the surface is a critical factor determining the nature of the interfacial interactions. Specifically, by growing CaRuO3/CaMnO3 heterostructures along the (111) instead of the (001) crystallographic axis, we achieve a 3-fold enhancement of the magnetization and involve the CaRuO3 layers in the ferromagnetism, which now spans both constituent materials. The stabilization of a net magnetic moment in CaRuO3 through strain effects has been long-sought but never consistently achieved, and our observations demonstrate the importance of interface engineering in the development of new functional heterostructures.

Anisotropic Magnon Spin Transport in Ultrathin Spinel Ferrite Thin Films─Evidence for Anisotropy in Exchange Stiffness.

Magnon-mediated spin flow in magnetically ordered insulators enables long-distance spin-based information transport with low dissipation. In the materials studied to date, no anisotropy has been observed in the magnon propagation length as a function of propagation direction. Here, we report measurements of magnon spin transport in a spinel ferrite, magnesium aluminum ferrite MgAl0.5Fe1.5O4 (MAFO), which has a substantial in-plane 4-fold magnetic anisotropy. We observe spin diffusion lengths > 0.8 µm at room temperature in 6 nm films, with spin diffusion lengths 30% longer along the easy axes compared to the hard axes. The sign of this difference is opposite to the effects just of anisotropy in the magnetic energy for a uniform magnetic state. We suggest instead that accounting for anisotropy in exchange stiffness is necessary to explain these results. These findings provide an approach for controlling magnon transport via strain, which opens new opportunities for designing magnonic devices.

Understanding Signatures of Emergent Magnetism in Topological Insulator/Ferrite Bilayers.

Magnetic insulator-topological insulator heterostructures have been studied in search of chiral edge states via proximity induced magnetism in the topological insulator, but these states have been elusive. We identified MgAl_{0.5}Fe_{1.5}O_{4}/Bi_{2}Se_{3} bilayers for a possible magnetic proximity effect. Electrical transport and polarized neutron reflectometry suggest a proximity effect, but structural data indicate a disordered interface as the origin of the magnetic response. Our results provide a strategy via correlation of microstructure with magnetic data to confirm a magnetic proximity effect.

Infantile Stage M Neuroblastoma With 11q Deletion, Mimicking Stage MS.

A 4-month-old boy with abdominal distension was diagnosed with adrenal neuroblastoma with numerous metastases to the liver and nodules in the skin and muscles. Marked hepatomegaly spontaneously regressed with decreasing tumor marker levels, and the final diagnosis was stage M based on radiologic findings confirming metastasis to the pancreas. The neuroblastoma did not have the MYCN amplification but had an 11q aberration. Chemotherapy was initiated at age 6 months with a successful response. Our case reflects the heterogenous clinical behavior of neuroblastoma and highlights the challenging issue of the difference between stage M and stage MS neuroblastoma in infants.

[Hematological neoplasia associated with primary mediastinal germ-cell tumor treated with hematopoietic stem cell transplantation].

The occurrence of a primary mediastinal germ cell tumor and hematological neoplasia provides a poor prognosis that is known to be fatal at a median of 6 months after onset. We report the case of a 15-year-old male who was treated with chemotherapy and hematopoietic cell transplantation based on a report of a surviving case. At diagnosis, the patient had an unresectable mediastinal tumor with elevated alpha-fetoprotein and human chorionic gonadotropin levels and acute megakaryoblastic leukemia. We prioritized treatment with chemotherapy for the tumor owing to the oncological emergency. We then performed leukemia induction therapy and achieved complete remission. Although we used CDDP in combination with intensive therapy, the mediastinal tumor grew too large for it to be safely resected. We transplanted bone marrow from the patient's human leukocyte antigen-haploidentical sibling upon conditioning with busulfan-melphalan. After 44 days, the leukemia recurred in the patient's central nervous system. This was followed by various post-transplant complications, and the patient died of organ failure that was associated with infectious diseases. At necropsy, a poorly engrafted bone marrow was observed. The mediastinal tumor was primarily necrotic, although some immature teratoma components were observed. No leukemic precursor cells were detected. Residual mediastinal tumors may be associated with the recurrence of leukemias. We seek a treatment strategy that enables early tumor resection and high-dose chemotherapy. Further case studies are warranted along with the development of effective treatment methods.

Ultralow Damping in Nanometer-Thick Epitaxial Spinel Ferrite Thin Films.

Pure spin currents, unaccompanied by dissipative charge flow, are essential for realizing energy-efficient nanomagnetic information and communications devices. Thin-film magnetic insulators have been identified as promising materials for spin-current technology because they are thought to exhibit lower damping compared with their metallic counterparts. However, insulating behavior is not a sufficient requirement for low damping, as evidenced by the very limited options for low-damping insulators. Here, we demonstrate a new class of nanometer-thick ultralow-damping insulating thin films based on design criteria that minimize orbital angular momentum and structural disorder. Specifically, we show ultralow damping in <20 nm thick spinel-structure magnesium aluminum ferrite (MAFO), in which magnetization arises from Fe3+ ions with zero orbital angular momentum. These epitaxial MAFO thin films exhibit a Gilbert damping parameter of ∼0.0015 and negligible inhomogeneous linewidth broadening, resulting in narrow half width at half-maximum linewidths of ∼0.6 mT around 10 GHz. Our findings offer an attractive thin-film platform for enabling integrated insulating spintronics.

Anti-Influenza Virus Activity of Adlay Tea Components.

Our previous study showed anti-influenza virus activity in adlay tea prepared from adlay seeds, naked barley seeds, soybean, and cassia seeds. In this study, we evaluated the anti-influenza virus activity of each component of this tea and analyzed their active ingredients. Each component was roasted and extracted in hot water; the extracts were tested for antiviral activity and their mechanisms of action were studied. All the tea components showed antiviral activity against the H1N1 and H3N2 influenza subtypes and against influenza B. The viral stages inhibited by the components were virus adsorption and replication in proliferative process, suggesting that the action mechanisms of the components might differ from those of oseltamivir acid. Of the tea components, soybean showed the strongest activity. Therefore, we analyzed its active ingredients by liquid chromatography quadruple time-of-flight mass spectrometry (LC/qTOF-MS) and daidzein and glycitein were detected as active ingredients. Here, anti-influenza virus action of glycitein was the first report.

Thermal E/ Z Isomerization in First Generation Molecular Motors.

Determination of a thermal E/ Z isomerization barrier of first generation molecular motors is reported. Stable ( E)-1a directly converts to stable ( Z)-1c without photochemical E/ Z isomerization. The activation Gibbs energy of the isomerization was determined to be 123 kJ mol-1 by circular dichroism spectral changes. Density functional theory calculations show that ( Z)-1c is ∼11.4 kJ mol-1 more stable than ( E)-1a.

Inhibition of influenza virus replication by adlay tea.

BACKGROUND: The present study was conducted aiming to examine the antiviral activity of adlay tea and its components against influenza viruses. We further aimed to clarify the mechanism by which these components regulate virus replication. RESULTS: Adlay tea at a concentration suitable for drinking inhibited the multiplication of influenza viruses. Moreover, our results suggest that individual components of the tea had antiviral activities against the influenza A/PR/8/34 virus. Adlay tea inhibited multiplication of the H1N1, H3N2 and B types of influenza virus, including oseltamivir-resistant viruses. In addition, adlay tea inhibited influenza infection during the periods of virus adsorption to the cell and virus replication. Adlay tea did not suppress hemagglutination inhibition or cell fusion, although it slightly inhibited virus binding to Malin Darby canine kidney cells. Furthermore, our findings suggest that the antiviral compounds included in adlay tea were ingredients other than polyphenols and that there were several types of effective compounds in adlay tea inhibiting several steps of viral replication. CONCLUSION: The results of the present study demonstrate that adlay tea had antiviral effects against influenza viruses. Our findings with respect to adlay tea suggest that the polyphenols might have a small influence on its antiviral activity and that other ingredients might have more influence. © 2017 Society of Chemical Industry.

Tuning Perpendicular Magnetic Anisotropy by Oxygen Octahedral Rotations in (La_{1-x}Sr_{x}MnO_{3})/(SrIrO_{3}) Superlattices.

Perpendicular magnetic anisotropy (PMA) plays a critical role in the development of spintronics, thereby demanding new strategies to control PMA. Here we demonstrate a conceptually new type of interface induced PMA that is controlled by oxygen octahedral rotation. In superlattices comprised of La_{1-x}Sr_{x}MnO_{3} and SrIrO_{3}, we find that all superlattices (0≤x≤1) exhibit ferromagnetism despite the fact that La_{1-x}Sr_{x}MnO_{3} is antiferromagnetic for x>0.5. PMA as high as 4×10^{6} erg/cm^{3} is observed by increasing x and attributed to a decrease of oxygen octahedral rotation at interfaces. We also demonstrate that oxygen octahedral deformation cannot explain the trend in PMA. These results reveal a new degree of freedom to control PMA, enabling discovery of emergent magnetic textures and topological phenomena.

Mangiferin, a novel nuclear factor kappa B-inducing kinase inhibitor, suppresses metastasis and tumor growth in a mouse metastatic melanoma model.

Advanced metastatic melanoma, one of the most aggressive malignancies, is currently without reliable therapy. Therefore, new therapies are urgently needed. Mangiferin is a naturally occurring glucosylxanthone and exerts many beneficial biological activities. However, the effect of mangiferin on metastasis and tumor growth of metastatic melanoma remains unclear. In this study, we evaluated the effect of mangiferin on metastasis and tumor growth in a mouse metastatic melanoma model. We found that mangiferin inhibited spontaneous metastasis and tumor growth. Furthermore, mangiferin suppressed the nuclear translocation of nuclear factor kappa B (NF-κB) and expression of phosphorylated NF-κB-inducing kinase (NIK), inhibitor of kappa B kinase (IKK), and inhibitor of kappa B (IκB) and increases the expression of IκB protein in vivo. In addition, we found that mangiferin inhibited the expression of matrix metalloproteinases (MMPs) and very late antigens (VLAs) in vivo. Mangiferin treatment also increased the expression of cleaved caspase-3, cleaved Poly ADP ribose polymerase-1 (PARP-1), p53 upregulated modulator of apoptosis (PUMA), p53, and phosphorylated p53 proteins, and decreased the expression of Survivin and Bcl-associated X (Bcl-xL) proteins in vivo. These results indicate that mangiferin selectivity suppresses the NF-κB pathway via inhibition of NIK activation, thereby inhibiting metastasis and tumor growth. Importantly, the number of reported NIK selective inhibitors is limited. Taken together, our data suggest that mangiferin may be a potential therapeutic agent with a new mechanism of targeting NIK for the treatment of metastatic melanoma.

Survival impact of pathologic features after salvage lung resection following definitive chemoradiotherapy or systemic therapy for initially unresectable lung cancer.

PURPOSE: Salvage surgery for primary lung cancer is expected to become increasingly common. This study aimed to clarify the survival impact of pathologic characteristics after salvage surgery. METHODS: Consecutive patients who underwent salvage surgery following definitive chemoradiotherapy or systemic therapy for initially unresectable lung cancer from 2010 to 2020 were enrolled in this study. The tumor slides were reviewed to determine the size of the tumor bed and the proportions of viable tumor, necrosis, and stroma. RESULTS: A total of 23 patients were evaluated, and 18 had clinical stage IIIB-IV disease. Six received chemoradiotherapy and 17 received systemic therapy alone. A major pathologic response (MPR, ≤ 10% of viable tumor) was observed in 6 patients, and 4 patients achieved a pathological complete response. The 3-year overall and recurrence-free survival rates (OS and RFS) were 78.6% and 59.2%, respectively. There was no significant difference in OS between patients with and without MPR, and even non-MPR patients achieved a favorable 3-year OS of 70.2%. Meanwhile, patients with high (≥ 30%) stroma showed significantly better OS than those with low (< 30%) stroma (3-year OS: 100% vs. 23.3%, p < 0.001). CONCLUSIONS: This study showed that the proportion of stroma can be useful for predicting long-term survival after salvage surgery. Further large-scale studies are warranted to confirm the current findings.

Familial and early recurrent pheochromocytoma in a child with a novel in-frame duplication variant of VHL.

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors often linked to underlying genetic variants. Genetic analysis can promote gene-adjusted, specific follow-up, and surveillance protocols for both patients and their families at risk. We report the case of a 7-yr-old boy with bilateral pheochromocytoma, which recurred a year after partial adrenalectomy. The patient's father developed bilateral pheochromocytomas at 25 yr of age. Both individuals possessed a novel heterogeneous in-frame duplication germline variant of VHL, yet neither exhibited other clinical manifestations of von Hippel-Lindau disease (VHL). Traditionally, VHL missense mutations have been associated with a higher risk of PPGL development, whereas truncating mutations typically confer a lower risk. In-frame duplication variants are rarely observed in patients with VHL but may lead to changes in the three-dimensional structure of the translated protein, similar to truncating variants. Our analysis suggests that these in-frame duplications of amino acids in specific regions may cause pheochromocytomas in a manner similar to missense variants. Further accumulation of VHL cases with various genotypes and standardized open-access worldwide databases, including longitudinal and specific clinical data linked to genotypes, is required. It is crucial to consider genetic analyses for pediatricians who may diagnose childhood-onset PPGL.

Dynamic chest radiographic evaluation of the effects of tiotropium/olodaterol combination therapy in chronic obstructive pulmonary disease: the EMBODY study protocol for an open-label, prospective, single-centre, non-controlled, comparative study.

INTRODUCTION: To date, there is limited evidence on the effects of bronchodilators on respiratory dynamics in chronic obstructive pulmonary disease (COPD). Dynamic chest radiography (DCR) is a novel radiographic modality that provides real-time, objective and quantifiable kinetic data, including changes in the lung area (Rs), tracheal diameter, diaphragmatic kinetics and pulmonary ventilation during respiration, at a lower radiation dose than that used by fluoroscopic or CT imaging. However, the therapeutic effect of dual bronchodilators on respiratory kinetics, such as chest wall dynamics and respiratory muscle function, has not yet been prospectively evaluated using DCR. AIM: This study aims to evaluate the effects of bronchodilator therapy on respiratory kinetics in patients with COPD using DCR. METHODS AND ANALYSIS: This is an open-label, prospective, single-centre, non-controlled, comparative study. A total of 35 patients with COPD, aged 40-85 years, with a forced expiratory volume in the first second of 30-80%, will be enrolled. After a 2-4 weeks washout period, patients will receive tiotropium/olodaterol therapy for 6 weeks. Treatment effects will be evaluated based on DCR findings, pulmonary function test results and patient-related outcomes obtained before and after treatment. The primary endpoint is the change in Rs after therapy. The secondary endpoints include differences in other DCR parameters (diaphragmatic kinetics, tracheal diameter change and maximum pixel value change rate), pulmonary function test results and patient-related outcomes between pre-therapy and post-therapy values. All adverse events will be reported. ETHICS AND DISSEMINATION: Ethical approval for this study was obtained from the Ethics Committee of Chiba University Hospital. The results of this trial will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: jRCTs032210543.

Synthesis of multifunctional amorphous metallic shell on crystalline metallic nanoparticles.

Colloidal nanoparticles can be coated with a conformal shell to form multifunctional nanoparticles. For instance, plasmonic, magnetic, and catalytic properties, chemical stability and biocompatibility can be mixed and matched. Here, a facile synthesis for depositing metal boride amorphous coatings on colloidal metallic nanocrystals is introduced. The synthesis is independent of core size, shape, and composition. We have found that the shell synthesis is limited to nanoparticles capped with short molecular weight and low binding energy ligands, and does not work with polyvinylpyrrolidone (PVP)-coated Ag nanoparticles or thiol-coated Au nanoparticles. Shell thickness can be as thin as 3 nm with no apparent pinholes. High pressure studies show that the coatings are highly resistant to crystallization and are strongly bonded to the crystalline core. By choosing either CoB or NiB for the coating, the composite nanoparticles can be either ferromagnetic or paramagnetic at room temperature, respectively.

Hybrid spin Hall nano-oscillators based on ferromagnetic metal/ferrimagnetic insulator heterostructures.

Spin-Hall nano-oscillators (SHNOs) are promising spintronic devices to realize current controlled GHz frequency signals in nanoscale devices for neuromorphic computing and creating Ising systems. However, traditional SHNOs devices based on transition metals have high auto-oscillation threshold currents as well as low quality factors and output powers. Here we demonstrate a new type of hybrid SHNO based on a permalloy (Py) ferromagnetic-metal nanowire and low-damping ferrimagnetic insulator, in the form of epitaxial lithium aluminum ferrite (LAFO) thin films. The superior characteristics of such SHNOs are associated with the excitation of larger spin-precession angles and volumes. We further find that the presence of the ferrimagnetic insulator enhances the auto-oscillation amplitude of spin-wave edge modes, consistent with our micromagnetic modeling. This hybrid SHNO expands spintronic applications, including providing new means of coupling multiple SHNOs for neuromorphic computing and advancing magnonics.

A puzzling insensitivity of magnon spin diffusion to the presence of 180-degree domain walls.

We present room-temperature measurements of magnon spin diffusion in epitaxial ferrimagnetic insulator MgAl0.5Fe1.5O4 (MAFO) thin films near zero applied magnetic field where the sample forms a multi-domain state. Due to a weak uniaxial magnetic anisotropy, the domains are separated primarily by 180° domain walls. We find, surprisingly, that the presence of the domain walls has very little effect on the spin diffusion - nonlocal spin transport signals in the multi-domain state retain at least 95% of the maximum signal strength measured for the spatially-uniform magnetic state, over distances at least five times the typical domain size. This result is in conflict with simple models of interactions between magnons and static domain walls, which predict that the spin polarization carried by the magnons reverses upon passage through a 180° domain wall.

Ultra-thin lithium aluminate spinel ferrite films with perpendicular magnetic anisotropy and low damping.

Ultra-thin films of low damping ferromagnetic insulators with perpendicular magnetic anisotropy have been identified as critical to advancing spin-based electronics by significantly reducing the threshold for current-induced magnetization switching while enabling new types of hybrid structures or devices. Here, we have developed a new class of ultra-thin spinel structure Li0.5Al1.0Fe1.5O4 (LAFO) films on MgGa2O4 (MGO) substrates with: 1) perpendicular magnetic anisotropy; 2) low magnetic damping and 3) the absence of degraded or magnetic dead layers. These films have been integrated with epitaxial Pt spin source layers to demonstrate record low magnetization switching currents and high spin-orbit torque efficiencies. These LAFO films on MGO thus combine all of the desirable properties of ferromagnetic insulators with perpendicular magnetic anisotropy, opening new possibilities for spin based electronics.

Design, synthesis, and biological evaluation of 4-arylmethyl-1-phenylpyrazole and 4-aryloxy-1-phenylpyrazole derivatives as novel androgen receptor antagonists.

A series of 4-arylmethyl-1-phenylpyrazole and 4-aryloxy-1-phenylpyrazole compounds B were designed, synthesized, and evaluated for their potential as new-generation androgen receptor (AR) antagonists therapeutically effective against castration-resistant prostate cancer (CRPC). Introduction of a bulky amide substituent (R(2)) to the terminal aryl ring of the 4-arylmethyl group favored the reduction of agonistic activity and improved the pharmacokinetic (PK) properties. Similarly, introduction of a bulky substituent in the 4-aryloxy derivatives also resulted in improved PK properties. Compounds 28 h and 44b exhibited potent antitumor effects against a CRPC model of LNCaP-hr cell line in a mouse xenograft model. On the contrary, bicalutamide showed only partial suppression of tumor growth. These results suggest that the novel pyrazole derivatives are new-generation AR antagonists, different from the 'first-generation' antagonists such as bicalutamide in a CRPC treatment model.