Colossal angular magnetoresistance in ferrimagnetic nodal-line semiconductors.

Efficient magnetic control of electronic conduction is at the heart of spintronic functionality for memory and logic applications1,2. Magnets with topological band crossings serve as a good material platform for such control, because their topological band degeneracy can be readily tuned by spin configurations, dramatically modulating electronic conduction3-10. Here we propose that the topological nodal-line degeneracy of spin-polarized bands in magnetic semiconductors induces an extremely large angular response of magnetotransport. Taking a layered ferrimagnet, Mn3Si2Te6, and its derived compounds as a model system, we show that the topological band degeneracy, driven by chiral molecular orbital states, is lifted depending on spin orientation, which leads to a metal-insulator transition in the same ferrimagnetic phase. The resulting variation of angular magnetoresistance with rotating magnetization exceeds a trillion per cent per radian, which we call colossal angular magnetoresistance. Our findings demonstrate that magnetic nodal-line semiconductors are a promising platform for realizing extremely sensitive spin- and orbital-dependent functionalities.

Characterization of Ginkgo biloba Leaf Flavonoids as Neuroexocytosis Regulators.

Ginkgo biloba leaf (GBL) is known as a potential source of bioactive flavonoids, such as quercetin, arresting the neuronal soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-zippering. Here, the GBL flavonoids were isolated in two different manners and then examined for their bioactivity, physicochemical stability, and biocompatibility. The majority of flavonoids in the non-hydrolyzed and acidolyzed isolates, termed non-hydrolyzed isolate (NI) and acidolyzed isolate (AI) hereafter, were rich in flavonol glycosides and aglycones, respectively. Glycosidic/aglyconic quercetin and kaempferol were abundant in both NI and AI, whereas a little of apigenin, luteolin, and isorhamnetin were found in AI. NI was more thermostable in all pH ranges than quercetin, kaempferol, and AI. NI and AI both inhibited neurotransmitter release from differentiated neuronal PC-12 cells. NI and AI showed 1/2-1/3 lower EC50/CC50 values than quercetin and kaempferol. The NI and AI exhibited no toxicity assessed by the tests on chorioallantoic membranes of hen's eggs, removing toxicological concerns of irritation potential. Moreover, GBL isolates, particularly AI, showed antioxidant and anti-inflammatory activities in the use below the CC50 levels. Taken together, these results suggest that GBL isolates that are rich in antioxidant flavonoids are effective anti-neuroexocytotic agents with high stability and low toxicity.

Green fluorescence protein-based content-mixing assay of SNARE-driven membrane fusion.

Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins mediate intracellular membrane fusion by forming a ternary SNARE complex. A minimalist approach utilizing proteoliposomes with reconstituted SNARE proteins yielded a wealth of information pinpointing the molecular mechanism of SNARE-mediated fusion and its regulation by accessory proteins. Two important attributes of a membrane fusion are lipid-mixing and the formation of an aqueous passage between apposing membranes. These two attributes are typically observed by using various fluorescent dyes. Currently available in vitro assay systems for observing fusion pore opening have several weaknesses such as cargo-bleeding, incomplete removal of unencapsulated dyes, and inadequate information regarding the size of the fusion pore, limiting measurements of the final stage of membrane fusion. In the present study, we used a biotinylated green fluorescence protein and streptavidin conjugated with Dylight 594 (DyStrp) as a Föster resonance energy transfer (FRET) donor and acceptor, respectively. This FRET pair encapsulated in each v-vesicle containing synaptobrevin and t-vesicle containing a binary acceptor complex of syntaxin 1a and synaptosomal-associated protein 25 revealed the opening of a large fusion pore of more than 5 nm, without the unwanted signals from unencapsulated dyes or leakage. This system enabled determination of the stoichiometry of the merging vesicles because the FRET efficiency of the FRET pair depended on the molar ratio between dyes. Here, we report a robust and informative assay for SNARE-mediated fusion pore opening.

Local and nonlocal Fraunhofer-like pattern from an edge-stepped topological surface Josephson current distribution.

We report a surface-dominant Josephson effect in superconductor-topological insulator-superconductor (S-TI-S) devices, where a Bi1.5Sb0.5Te1.7Se1.3 (BSTS) crystal flake was adopted as an intervening TI between Al superconducting electrodes. We observed a Fraunhofer-type critical current modulation in a perpendicular magnetic field in an Al-TI-Al junction for both local and nonlocal current biasing. Fraunhofer-type modulation of the differential resistance was also observed in a neighboring Au-TI-Au normal junction when it was nonlocally biased by the Al-TI-Al junction. In all cases, the Fraunhofer-like signal was highly robust to the magnetic field up to the critical field of the Al electrodes, corresponding to the edge-stepped nonuniform supercurrent density arising from the top and rough side surfaces of the BSTS flake, which strongly suggests that the Josephson coupling in a TI is established through the surface conducting channels that are topologically protected.

Valley-polarized interlayer conduction of anisotropic Dirac fermions in SrMnBi2.

We report the valley-selective interlayer conduction of SrMnBi(2) under in-plane magnetic fields. The c-axis resistivity of SrMnBi(2) shows clear angular magnetoresistance oscillations indicating coherent interlayer conduction. Strong fourfold variation of the coherent peak in the c-axis resistivity reveals that the contribution of each Dirac valley is significantly modulated by the in-plane field orientation. This originates from anisotropic Dirac Fermi surfaces with strong disparity in the momentum-dependent interlayer coupling. Furthermore, we found a signature of broken valley symmetry at high magnetic fields. These findings demonstrate that a quasi-two-dimensional anisotropic Dirac system can host a valley-polarized interlayer current through magnetic valley control.

Analysis of the Prognosis Outcomes and Treatment Delay Among ST-Segment Elevation Myocardial Infarction Patients in Emergency Department Based on the Presence of Symptoms Suggestive of COVID-19.

BACKGROUND: During COVID-19 pandemic, the emergency department (ED) was challenged to treat patients with COVID-19-related symptom. Therefore, the aim of this study was to investigate treatment delay and prognostic outcomes in ST-segment elevation myocardial infarction (STEMI) patients during COVID-19 pandemic due to isolation or precaution and compare it with pre-COVID-19 period. METHODS: This was a retrospective observation study using multicenter data with different case mix. Anonymized data were collected through each center's electronic medical data of common case report form. Primary outcomes were number and rate of in-hospital mortality within 28 days. Secondary outcomes were door-to-balloon time and length of stay in the ED. Kaplan-Meier estimation and Cox proportional hazard regression analysis were performed to determine impact of predictors on 28-day in-hospital mortality. RESULTS: Door-to-balloon time was longer in STEMI patients with COVID-19-related symptom(s) than those without symptom during the COVID-19 period (97.0 [74.8, 139.8] vs. 69.0 [55.0, 102.0] minutes, P<.001). However, there was no significant statistical difference in door-to-balloon time between STEMI patients with and without COVID-19-related symptom(s) during the pre-COVID-19 period (73.0 [61.0, 92.0] vs. 67.0 [54.5, 80.0] minutes, P=.2869). The 28-day mortality rate did not show a statistically significant difference depending on symptoms suggestive of COVID-19 during the pre-COVID-19 period (15.4% vs. 6.8%, P=.1257). However, it was significantly higher during the COVID-19 period (21.1% vs. 6.7%, P=.0102) in patients with COVID-19 suggestive symptoms than in patients without the symptoms. CONCLUSION: In Korea, symptoms suggestive of COVID-19 during the pandemic had a significant effect on the increase of door-to-balloon time and 28-day mortality in STEMI patients. Thus, health authorities need to make careful decision in designating symptoms indicated for isolation in ED based on opinions of various medical field experts.

Anisotropic Dirac fermions in a Bi square net of SrMnBi2.

We report the observation of highly anisotropic Dirac fermions in a Bi square net of SrMnBi(2), based on a first-principles calculation, angle-resolved photoemission spectroscopy, and quantum oscillations for high-quality single crystals. We found that the Dirac dispersion is generally induced in the (SrBi)(+) layer containing a double-sized Bi square net. In contrast to the commonly observed isotropic Dirac cone, the Dirac cone in SrMnBi(2) is highly anisotropic with a large momentum-dependent disparity of Fermi velocities of ~8. These findings demonstrate that a Bi square net, a common building block of various layered pnictides, provides a new platform that hosts highly anisotropic Dirac fermions.

Rigid platform for applying large tunable strains to mechanically delicate samples.

Response to uniaxial stress has become a major probe of electronic materials. Tunable uniaxial stress may be applied using piezoelectric actuators, and so far two methods have been developed to couple samples to actuators. In one, actuators apply force along the length of a free, beam-like sample, allowing very large strains to be achieved. In the other, samples are affixed directly to piezoelectric actuators, allowing the study of mechanically delicate materials. Here, we describe an approach that merges the two: thin samples are affixed to a substrate, which is then pressurized uniaxially using piezoelectric actuators. Using this approach, we demonstrate the application of large elastic strains to mechanically delicate samples: the van der Waals-bonded material FeSe and a sample of CeAuSb2 that was shaped with a focused ion beam.

Reduction of focal sweating by lipid nanoparticle-delivered myricetin.

Myricetin-a flavonoid capable of inhibiting the SNARE complex formation in neurons-reduces focal sweating after skin-application when delivers as encapsulated in lipid nanoparticles (M-LNPs). The stability of M-LNP enables efficient delivery of myricetin to sudomotor nerves located underneath sweat glands through transappendageal pathways while free myricetin just remained on the skin. Furthermore, release of myricetin from M-LNP is accelerated through lipase-/esterase-induced lipolysis in the skin-appendages, enabling uptake of myricetin by the surrounding cells. The amount of sweat is reduced by 55% after application of M-LNP (0.8 mg kg-1) on the mouse footpad. This is comparable to that of subcutaneously injected anticholinergic agents [0.25 mg kg-1 glycopyrrolate; 0.8 U kg-1 botulinum neurotoxin-A-type (BoNT/A)]. M-LNP neither shows a distal effect after skin-application nor induced cellular/ocular toxicity. In conclusion, M-LNP is an efficient skin-applicable antiperspirant. SNARE-inhibitory small molecules with suitable delivery systems have the potential to replace many BoNT/A interventions for which self-applications are preferred.

Magnetic field-tuned Fermi liquid in a Kondo insulator.

Kondo insulators are expected to transform into metals under a sufficiently strong magnetic field. The closure of the insulating gap stems from the coupling of a magnetic field to the electron spin, yet the required strength of the magnetic field-typically of order 100 T-means that very little is known about this insulator-metal transition. Here we show that Ce[Formula: see text]Bi[Formula: see text]Pd[Formula: see text], owing to its fortuitously small gap, provides an ideal Kondo insulator for this investigation. A metallic Fermi liquid state is established above a critical magnetic field of only [Formula: see text] 11 T. A peak in the strength of electronic correlations near [Formula: see text], which is evident in transport and susceptibility measurements, suggests that Ce[Formula: see text]Bi[Formula: see text]Pd[Formula: see text] may exhibit quantum criticality analogous to that reported in Kondo insulators under pressure. Metamagnetism and the breakdown of the Kondo coupling are also discussed.

Soluble N-Ethylmaleimide-Sensitive Factor Attachment Protein Receptor-Derived Peptides for Regulation of Mast Cell Degranulation.

Vesicle-associated V-soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins and target membrane-associated T-SNAREs (syntaxin 4 and SNAP-23) assemble into a core trans-SNARE complex that mediates membrane fusion during mast cell degranulation. This complex plays pivotal roles at various stages of exocytosis from the initial priming step to fusion pore opening and expansion, finally resulting in the release of the vesicle contents. In this study, peptides with the sequences of various SNARE motifs were investigated for their potential inhibitory effects against SNARE complex formation and mast cell degranulation. The peptides with the sequences of the N-terminal regions of vesicle-associated membrane protein 2 (VAMP2) and VAMP8 were found to reduce mast cell degranulation by inhibiting SNARE complex formation. The fusion of protein transduction domains to the N-terminal of each peptide enabled the internalization of the fusion peptides into the cells equally as efficiently as cell permeabilization by streptolysin-O without any loss of their inhibitory activities. Distinct subsets of mast cell granules could be selectively regulated by the N-terminal-mimicking peptides derived from VAMP2 and VAMP8, and they effectively decreased the symptoms of atopic dermatitis in mouse models. These results suggest that the cell membrane fusion machinery may represent a therapeutic target for atopic dermatitis.

Visualization of SNARE-Mediated Hemifusion between Giant Unilamellar Vesicles Arrested by Myricetin.

Neurotransmitters are released within a millisecond after Ca2+ arrives at an active zone. However, the vesicle fusion pathway underlying this synchronous release is yet to be understood. At the center of controversy is whether hemifusion, in which outer leaflets are merged while inner leaflets are still separated, is an on-pathway or off-pathway product of Ca2+-triggered exocytosis. Using the single vesicle fusion assay, we recently demonstrated that hemifusion is an on-pathway intermediate that immediately proceeds to full fusion upon Ca2+ triggering. It has been shown that the flavonoid myricetin arrests soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor (SNARE)-mediated vesicle fusion at hemifusion, but that the hemifused vesicles spontaneously convert to full fusion when the myricetin clamp is removed by the enzyme laccase. In the present study, we visualized SNARE-mediated hemifusion between two SNARE-reconstituted giant unilamellar vesicles (GUVs) arrested by myricetin. The large size of the GUVs enabled us to directly image the hemifusion between them. When two merging GUVs were labeled with different fluorescent dyes, GUV pairs showed asymmetric fluorescence intensities depending on the position on the GUV pair consistent with what is expected for hemifusion. The flow of lipids from one vesicle to the other was revealed with fluorescence recovery after photobleaching (FRAP), indicating that the two membranes had hemifused. These results support the hypothesis that hemifusion may be the molecular status that primes Ca2+-triggered millisecond exocytosis. This study represents the first imaging of SNARE-driven hemifusion between GUVs.

Co-expression of two heterologous lactate dehydrogenases genes in Kluyveromyces marxianus for l-lactic acid production.

Lactic acid (LA) is a versatile compound used in the food, pharmaceutical, textile, leather, and chemical industries. Biological production of LA is possible by yeast strains expressing a bacterial gene encoding l-lactate dehydrogenase (LDH). Kluyveromyces marxianus is an emerging non-conventional yeast with various phenotypes of industrial interest. However, it has not been extensively studied for LA production. In this study, K. marxianus was engineered to express and co-express various heterologous LDH enzymes that were reported to have different pH optimums. Specifically, three LDH enzymes originating from Staphylococcus epidermidis (SeLDH; optimal at pH 5.6), Lactobacillus acidophilus (LaLDH; optimal at pH 5.3), and Bos taurus (BtLDH; optimal at pH 9.8) were functionally expressed individually and in combination in K. marxianus, and the resulting strains were compared in terms of LA production. A strain co-expressing SeLDH and LaLDH (KM5 La+SeLDH) produced 16.0g/L LA, whereas the strains expressing those enzymes individually produced only 8.4 and 6.8g/L, respectively. This co-expressing strain produced 24.0g/L LA with a yield of 0.48g/g glucose in the presence of CaCO3. Our results suggest that co-expression of LDH enzymes with different pH optimums provides sufficient LDH activity under dynamic intracellular pH conditions, leading to enhanced production of LA compared to individual expression of the LDH enzymes.

Topological phase transition and quantum spin Hall edge states of antimony few layers.

While two-dimensional (2D) topological insulators (TI's) initiated the field of topological materials, only very few materials were discovered to date and the direct access to their quantum spin Hall edge states has been challenging due to material issues. Here, we introduce a new 2D TI material, Sb few layer films. Electronic structures of ultrathin Sb islands grown on Bi2Te2Se are investigated by scanning tunneling microscopy. The maps of local density of states clearly identify robust edge electronic states over the thickness of three bilayers in clear contrast to thinner islands. This indicates that topological edge states emerge through a 2D topological phase transition predicted between three and four bilayer films in recent theory. The non-trivial phase transition and edge states are confirmed for epitaxial films by extensive density-functional-theory calculations. This work provides an important material platform to exploit microscopic aspects of the quantum spin Hall phase and its quantum phase transition.

Possible flat band bending of the Bi1.5Sb0.5Te1.7Se1.3 crystal cleaved in an ambient air probed by terahertz emission spectroscopy.

We investigate an evolution of the surface electronic state of the Bi1.5Sb0.5Te1.7Se1.3 single crystal, which is one of the most bulk insulating topological insulators, by examining terahertz light emitted from the sample surface upon the illumination of the near-infrared femtosecond laser pulses. We find that the surface state with a flat band bending can appear in the course of the natural maturation process of the surface state in an ambient air. Furthermore, we demonstrate that the evolution of the surface electronic state can be accelerated, decelerated, or even stopped by controlling environmental conditions to contain different amount of H2O, in particular.

Quantum Oscillation Signatures of Pressure-induced Topological Phase Transition in BiTeI.

We report the pressure-induced topological quantum phase transition of BiTeI single crystals using Shubnikov-de Haas oscillations of bulk Fermi surfaces. The sizes of the inner and the outer FSs of the Rashba-split bands exhibit opposite pressure dependence up to P = 3.35 GPa, indicating pressure-tunable Rashba effect. Above a critical pressure P ~ 2 GPa, the Shubnikov-de Haas frequency for the inner Fermi surface increases unusually with pressure, and the Shubnikov-de Haas oscillations for the outer Fermi surface shows an abrupt phase shift. In comparison with band structure calculations, we find that these unusual behaviors originate from the Fermi surface shape change due to pressure-induced band inversion. These results clearly demonstrate that the topological quantum phase transition is intimately tied to the shape of bulk Fermi surfaces enclosing the time-reversal invariant momenta with band inversion.

Anisotropic Terahertz Emission from Bi2Se3 Thin Films with Inclined Crystal Planes.

We investigate the surface states of topological insulator (TI) Bi2Se3 thin films grown on Si nanocrystals and Al2O3 substrates by using terahertz (THz) emission spectroscopy. Compared to bulk crystalline Bi2Te2Se, film TIs exhibit distinct behaviors in the phase and amplitude of emitted THz radiation. In particular, Bi2Se3 grown on Al2O3 shows an anisotropic response with a strong modulation of the THz signal in its phase. From x-ray diffraction, we find that the crystal plane of the Bi2Se3 films is inclined with respect to the plane of the Al2O3 substrate by about 0.27°. This structural anisotropy affects the dynamics of photocarriers and hence leads to the observed anisotropic response in the THz emission. Such relevance demonstrates that THz emission spectroscopy can be a sensitive tool to investigate the fine details of the surface crystallography and electrostatics of thin film TIs.

Atomic and electronic structure of an alloyed topological insulator, Bi1.5Sb0.5Te1.7Se1.3.

Bi2-xSbxTe3-ySey has been argued to exhibit both topological surface states and insulating bulk states, but has not yet been studied with local probes on the atomic scale. Here we report on the atomic and electronic structures of Bi1.5Sb0.5Te1.7Se1.3 studied using scanning tunnelling microscopy (STM) and spectroscopy (STS). Although there is significant surface disorder due to alloying of constituent atoms, cleaved surfaces of the crystals present a well-ordered hexagonal lattice with 10 Å high quintuple layer steps. STS results reflect the band structure and indicate that the surface state and Fermi energy are both located inside the energy gap. In particular, quasi-particle interference patterns from electron scattering demonstrate that the surface states possess linear dispersion and chirality from spin texture, thus verifying its topological nature. This finding demonstrates that alloying is a promising route to achieve full suppression of bulk conduction in topological insulators whilst keeping the topological surface state intact.