Imaging the Breakdown and Restoration of Topological Protection in Magnetic Topological Insulator MnBi2Te4.

Quantum anomalous Hall (QAH) insulators transport charge without resistance along topologically protected chiral 1D edge states. Yet, in magnetic topological insulators to date, topological protection is far from robust, with zero-magnetic field QAH effect only realized at temperatures an order of magnitude below the Néel temperature TN, though small magnetic fields can stabilize QAH effect. Understanding why topological protection breaks down is therefore essential to realizing QAH effect at higher temperatures. Here a scanning tunneling microscope is used to directly map the size of exchange gap (Eg,ex) and its spatial fluctuation in the QAH insulator 5-layer MnBi2Te4. Long-range fluctuations of Eg,ex are observed, with values ranging between 0 (gapless) and 70 meV, appearing to be uncorrelated to individual surface point defects. The breakdown of topological protection is directly imaged, showing that the gapless edge state, the hallmark signature of a QAH insulator, hybridizes with extended gapless regions in the bulk. Finally, it is unambiguously demonstrated that the gapless regions originate from magnetic disorder, by demonstrating that a small magnetic field restores Eg,ex in these regions, explaining the recovery of topological protection in magnetic fields. The results indicate that overcoming magnetic disorder is the key to exploiting the unique properties of QAH insulators.

A visual and reversible nanoprobe for rapid and on-site determination of hexavalent chromium and lysine based on dual-emission carbon quantum dots coupled with smartphone.

A straightforward, largely instrument-free, smartphone-based analytical strategy for hexavalent chromium and lysine (Lys) on-site detection via exploitation of dual-emission carbon quantum dots (DECQDs) has been demonstrated. DECQDs show dual-emission peaks at 439 and 630 nm with the excitation at 375 nm. As a dual-mode detection probe, the fluorescence and ultraviolet adsorption spectra of DECQDs vary with hexavalent chromium concentrations. Most importantly, Lys can restore the fluorescence of the hexavalent chromium added DECQD nanoprobe and change the color of the probe under natural light. At the same time, based on the participation of smartphones, the prepared DECQD probes favor the establishment of visual smart sensors that can also be used for the in-situ detection of targets. The on-site quantitative analysis exhibited a linear range of 5.3-320 µM with a detection limit of 1.6 µM towards Cr(VI) and the differentiation of Lys variation from 1 to 75 mM with a detection limit of 0.3 mM. The probe has been applied for the first time to enable vision-based colorimetric in complex samples such as water, milk and egg. The recoveries of Cr(VI) and Lys in real samples were between 90 and 104%, and the relative standard deviation (RSD) was as low as 0.4%. This work offers new perspectives for fundamental understanding and new design of functional luminescent materials that are applicable for food-safety and rapid and intelligent inspection. A straightforward, large instrument-free, smartphone-based analytical strategy with dual-emission carbon quantum dots was developed for hexavalent chromium and Lys on-site detection via fluorescent and colorimetric twofold readout measure.

Integration of Metal-Organic Frameworks with Bi-Nanoprobes as Dual-Emissive Ratiometric Sensors for Fast and Highly Sensitive Determination of Food Hazards.

Functional nanoprobes which detect specific food hazards quickly and simply are still in high demand in the field of food-safety inspection research. In the present work, a dual-emission metal-organic framework-based ratiometric fluorescence probe was integrated to detect Cu2+ and Pb2+ with rapidness and ease. Specifically, quantum dots (QDs) and carbon quantum dots (CQDs) were successfully embedded into zeolitic imidazolate framework-67 (ZIF-67) to function as a novel ratiometric fluorescent sensing composite. The ratiometric fluorescence signal of CQDs/QDs@ZIF-67 was significantly aligned with the concentration of metal ions to give an extremely low detection limit of 0.3324 nM. The highly sensitive and selective CQDs/QDs@ZIF-67 composite showed potential for the rapid and cost-effective detection of two metal ions.

Large Magnetic Gap in a Designer Ferromagnet-Topological Insulator-Ferromagnet Heterostructure.

Combining magnetism and nontrivial band topology gives rise to quantum anomalous Hall (QAH) insulators and exotic quantum phases such as the QAH effect where current flows without dissipation along quantized edge states. Inducing magnetic order in topological insulators via proximity to a magnetic material offers a promising pathway toward achieving the QAH effect at a high temperature for lossless transport applications. One promising architecture involves a sandwich structure comprising two single-septuple layers (1SL) of MnBi2 Te4 (a 2D ferromagnetic insulator) with ultrathin few quintuple layer (QL) Bi2 Te3 in the middle, and it is predicted to yield a robust QAH insulator phase with a large bandgap greater than 50 meV. Here, the growth of a 1SL MnBi2 Te4 /4QL Bi2 Te3 /1SL MnBi2 Te4 heterostructure via molecular beam epitaxy is demonstrated and the electronic structure probed using angle-resolved photoelectron spectroscopy. Strong hexagonally warped massive Dirac fermions and a bandgap of 75 ± 15 meV are observed. The magnetic origin of the gap is confirmed by the observation of the exchange-Rashba effect, as well as the vanishing bandgap above the Curie temperature, in agreement with density functional theory calculations. These findings provide insights into magnetic proximity effects in topological insulators and reveal a promising platform for realizing the QAH effect at elevated temperatures.

Formation of a Stable Surface Oxide in MnBi2Te4 Thin Films.

Understanding the air stability of MnBi2Te4 thin films is crucial for the development and long-term operation of electronic devices based on magnetic topological insulators. In the present work, we study MnBi2Te4 thin films upon exposure to the atmosphere using a combination of synchrotron-based photoelectron spectroscopy, room-temperature electrical transport, and atomic force microscopy to determine the oxidation process. After 2 days of air exposure, a 2 nm thick oxide passivates the surface, corresponding to the oxidation of only the top two surface layers, with the underlying layers preserved. This protective oxide layer results in samples that still exhibit metallic conduction even after several days of air exposure. Furthermore, the work function decreases from 4.4 eV for pristine MnBi2Te4 to 4.0 eV after the formation of the oxide, along with only a small shift in the core levels, indicating minimal doping as a result of air exposure. With the oxide confined to the top surface layers, and the underlying layers preserved, it may be possible to explore new avenues in how to handle, prepare, and passivate future MnBi2Te4 devices.

Crossover from 2D Ferromagnetic Insulator to Wide Band Gap Quantum Anomalous Hall Insulator in Ultrathin MnBi2Te4.

Intrinsic magnetic topological insulators offer low disorder and large magnetic band gaps for robust magnetic topological phases operating at higher temperatures. By controlling the layer thickness, emergent phenomena such as the quantum anomalous Hall (QAH) effect and axion insulator phases have been realized. These observations occur at temperatures significantly lower than the Néel temperature of bulk MnBi2Te4, and measurement of the magnetic energy gap at the Dirac point in ultrathin MnBi2Te4 has yet to be achieved. Critical to achieving the promise of this system is a direct measurement of the layer-dependent energy gap and verification of a temperature-dependent topological phase transition from a large band gap QAH insulator to a gapless TI paramagnetic phase. Here we utilize temperature-dependent angle-resolved photoemission spectroscopy to study epitaxial ultrathin MnBi2Te4. We directly observe a layer-dependent crossover from a 2D ferromagnetic insulator with a band gap greater than 780 meV in one septuple layer (1 SL) to a QAH insulator with a large energy gap (>70 meV) at 8 K in 3 and 5 SL MnBi2Te4. The QAH gap is confirmed to be magnetic in origin, as it becomes gapless with increasing temperature above 8 K.

Recent Progress on Luminescent Metal-Organic Framework-Involved Hybrid Materials for Rapid Determination of Contaminants in Environment and Food.

The high speed of contaminants growth needs the burgeoning of new analytical techniques to keep up with the continuous demand for monitoring and legislation on food safety and environmental pollution control. Metal-organic frameworks (MOFs) are a kind of advanced crystal porous materials with controllable apertures, which are self-assembled by organic ligands and inorganic metal nodes. They have the merits of large specific surface areas, high porosity and the diversity of structures and functions. Latterly, the utilization of metal-organic frameworks has attracted much attention in environmental protection and the food industry. MOFs have exhibited great value as sensing materials for many targets. Among many sensing methods, fluorometric sensing is one of the widely studied methods in the detection of harmful substances in food and environmental samples. Fluorometric detection based on MOFs and its functional materials is currently one of the most key research subjects in the food and environmental fields. It has gradually become a hot research direction to construct the highly sensitive rapid sensors to detect harmful substances in the food matrix based on metal-organic frameworks. In this paper, we introduced the synthesis and detection application characteristics (absorption, fluorescence, etc.) of metal-organic frameworks. We summarized their applications in the MOFs-based fluorometric detection of harmful substances in food and water over the past few years. The harmful substances mainly include heavy metals, organic pollutants and other small molecules, etc. On this basis, the future development and possible application of the MOFs have prospected in this review paper.

Echocardiography in nonclinical studies: Where are we?

Echocardiography is a powerful, noninvasive tool used both in clinical and nonclinical settings, including in drug development. When used appropriately, it can provide valuable translational information about pharmacodynamics, safety pharmacology, or toxicology, helping to define no-observed-adverse-effect levels and providing guidance for clinical monitoring and dose selection. Echocardiography is advantageous in conducting longitudinal studies and reducing the number of animals used in safety assessments. To this end, there has been no clear enunciation of what constitutes appropriate use of this imaging technology in a nonclinical drug development setting. In this review, we describe the use of echocardiography in nonclinical studies in regulatory submissions to the US Food and Drug Administration Center for Drug Evaluation and Research. In addition, we discuss three main areas: the operator, image acquisition, and image analysis, where variability may affect the reliability of information generated in an echocardiography study. As a path forward, our recommendation is for a multi-disciplinary expert working group to establish guidelines for education and credentialing of nonclinical echocardiographers as well as quality assurance standards for nonclinical echocardiography labs.

Ultra-Stable UiO-66 Involved Molecularly Imprinted Polymers for Specific and Sensitive Determination of Tyramine Based on Quartz Crystal Microbalance Technology.

A rapid method was developed to determine the content of tyramine in food on the basis of the combination of molecular imprinting technique and the metal-organic frameworks. We developed the new molecular imprinted polymers based on metal-organic frameworks UiO-66 (named UiO-66@MIPs) as the sensing recognition element, the non-molecular imprinted polymers based on UiO-66 (named UiO-66@NIPs) was synthesized according the same steps without tyramine for comparison. The characterization of obtained UiO-66@MIPs was investigated through a series of characterization experiments. The results indicated that the octahedral shaped UiO-66 was encapsulated in the sol-gel polymer film, with a desirable thermal stability and possessed a specific surface area (SSA) of 994.3 m2·g-1. The imprinting factor of the UiO-66@MIPs for tyramine was 1.956 in static experiment. This indicates the synthesized UiO-66@MIPs have outstanding performance compered to UiO-66@NIPs on the static adsorption quantity and selective adsorption affinity. It's to make use of advantages of the synthetic materials to develop a quartz crystal microbalance (QCM) sensor for the sensitive detection of tyramine. The detection limit of the system was 61.65 µg·L-1 within measurable concentration range from 80 to 500 µg·L-1. The prepared QCM sensor was verified in selectivity and application. The UiO-66@MIPs possess good behavior on selectivity, absorptivity, and chemical stability, so the UiO-66@MIPs achieve accurate and rapid trace detection of biogenic amines in food combining with the quartz crystal microbalance.

Nanomosaic of Topological Dirac States on the Surface of Pb5Bi24Se41 Observed by Nano-ARPES.

We have performed scanning angle-resolved photoemission spectroscopy with a nanometer-sized beam spot (nano-ARPES) on the cleaved surface of Pb5Bi24Se41, which is a member of the (PbSe)5(Bi2Se3)3 m homologous series (PSBS) with m = 4 consisting of alternate stacking of the topologically trivial insulator PbSe bilayer and four quintuple layers (QLs) of the topological insulator Bi2Se3. This allows us to visualize a mosaic of topological Dirac states at a nanometer scale coming from the variable thickness of the Bi2Se3 nanoislands (1-3 QLs) that remain on top of the PbSe layer after cleaving the PSBS crystal, because the local band structure of topological origin changes drastically with the thickness of the Bi2Se3 nanoislands. A comparison of the local band structure with that in ultrathin Bi2Se3 films on Si(111) gives us further insights into the nature of the observed topological states. This result demonstrates that nano-ARPES is a very useful tool for characterizing topological heterostructures.

Ultrathin Bismuth Film on High-Temperature Cuprate Superconductor Bi2Sr2CaCu2O8+δ as a Candidate of a Topological Superconductor.

One of the key challenges in condensed-matter physics is to establish a topological superconductor that hosts exotic Majorana fermions. Although various heterostructures consisting of conventional BCS (Bardeen-Cooper-Schrieffer) superconductors as well as doped topological insulators were intensively investigated, no conclusive evidence for Majorana fermions has been provided. This is mainly because of their very low superconducting transition temperatures ( Tc) and small superconducting-gap magnitude. Here, we report a possible realization of topological superconductivity at very high temperatures in a hybrid of Bi(110) ultrathin film and copper oxide superconductor Bi2Sr2CaCu2O8+δ (Bi2212). Using angle-resolved photoemission spectroscopy and scanning tunneling microscopy, we found that three-bilayer-thick Bi(110) on Bi2212 exhibits a proximity-effect-induced s-wave energy gap as large as 7.5 meV which persists up to Tc of Bi2212 (85 K). The small Fermi energy and strong spin-orbit coupling of Bi(110), together with the large pairing gap and high Tc, make this system a prime candidate for exploring stable Majorana fermions at very high temperatures.

Ultrathin Bismuth Film on 1T-TaS2: Structural Transition and Charge-Density-Wave Proximity Effect.

We have fabricated bismuth (Bi) ultrathin films on a charge-density-wave (CDW) compound 1T-TaS2 and elucidated electronic states by angle-resolved photoemission spectroscopy and first-principles band-structure calculations. We found that the Bi film on 1T-TaS2 undergoes a structural transition from (111) to (110) upon reducing the film thickness, accompanied by a drastic change in the energy band structure. We also revealed that while two-bilayer-thick Bi(110) film on Si(111) is characterized by a dispersive band touching the Fermi level ( EF), the energy band of the same film on 1T-TaS2 exhibits holelike dispersion with a finite energy gap at EF. We discuss the origin of such intriguing differences in terms of the CDW proximity effect.

Safety of antisense oligonucleotide and siRNA-based therapeutics.

Oligonucleotide-based therapy is an active area of drug development designed to treat a variety of gene-specific diseases. Two of the more promising platforms are the antisense oligonucleotides (ASOs) and short interfering RNAs (siRNAs), both of which are often directed against similar targets. In light of recent reports on clinical trials of severe thrombocytopenia with two different ASO drugs and increased peripheral neuropathy with an siRNA drug, we compared and contrasted the specific safety characteristics of these two classes of oligonucleotide therapeutic. The objectives were to assess factors that could contribute to the specific toxicities observed with these two classes of promising drugs, and get a better understanding of the potential mechanism(s) responsible for these rare, but serious, adverse events.

Human platelets pathogen reduced with riboflavin and ultraviolet light do not cause acute lung injury in a two-event SCID mouse model.

BACKGROUND: Pathogen reduction technologies (PRTs) can induce platelet (PLT) lesions that reduce PLT survival and recovery from circulation and may be associated with acute lung injury (ALI). STUDY DESIGN AND METHODS: Human PLTs (hPLTs) in plasma with or without single or multiple Mirasol PRT treatments were assessed in vitro by aggregation and percentage of P-selectin expression. In vivo studies included PLT recovery in SCID mice and assessment of ALI in a two-event mouse model in which the sensitizing event was lipopolysaccharide injection and the second event was infusion of Mirasol-treated hPLTs. RESULTS: A single-dose Mirasol treatment (5 J/cm(2) ) did not induce any change in aggregation in response to adenosine 5'-diphosphate (ADP) while a five-times-repeat Mirasol treatment (5×) increased aggregation response to low concentration of ADP. Mirasol PLTs (1×-5×) had increased percentage of P-selectin-positive PLTs after treatment and decreased aggregation with TRAP as the agonist. In vivo recovery in SCID mice was reduced extensively with Mirasol treatments (1× and 5×). In the two-event model of ALI, only the 5× Mirasol PLTs accumulated in the lung and this was not accompanied by changes in lung histology or increases in MIP-2 levels in bronchoalveolar lavage fluid. CONCLUSIONS: Mirasol PRT treatment induced PLT activation and reduced in vivo recovery in a SCID mouse model of transfusion. In our two-event mouse model of ALI, the 5× Mirasol hPLTs accumulated in the lung, but did not cause signs of ALI. The 1× Mirasol treatment did not lead to PLT lung accumulation or ALI in this model.

In vitro and in vivo characterization of ultraviolet light C-irradiated human platelets in a 2 event mouse model of transfusion.

UV-based pathogen reduction technologies have been developed in recent years to inactivate pathogens and contaminating leukocytes in platelet transfusion products in order to prevent transfusion-transmitted infections and alloimmunization. UVC-based technology differs from UVA or UVB-based technologies in that it uses a specific wavelength at 254 nm without the addition of any photosensitizers. Previously, it was reported that UVC irradiation induces platelet aggregation and activation. To understand if UVC-induced changes of platelet quality correlate with potential adverse events when these platelets are transfused into animals, we used a 2-event SCID mouse model in which the predisposing event was LPS treatment and the second event was infusion of UVC-irradiated platelets. We analyzed lung platelet accumulation, protein content in bronchoalveolar lavage fluid as an indication of lung injury, and macrophage inflammatory protein-2 (MIP-2) release in mice received UVC-irradiated or untreated control platelets. Our results showed UVC-irradiated platelets accumulated in lungs of the mice in a dose-dependent manner. High-doses of UVC-irradiated platelets were sequestered in the lungs to a similar level as we previously reported for UVB-irradiated platelets. Unlike UVB-platelets, UVC-platelets did not lead to lung injury or induce MIP-2 release. This could potentially be explained by our observation that although UVC treatment activated platelet surface αIIbß3, it failed to activate platelet cells. It also suggests lung platelet accumulation and subsequent lung damage are due to different and separate mechanisms which require further investigation.

Activation of platelet protein kinase C by ultraviolet light B mediates platelet transfusion-related acute lung injury in a two-event animal model.

BACKGROUND: We recently reported that infusion of ultraviolet light B (UVB)-exposed human platelets (HPs) can be the second event that mediates acute lung injury (ALI) in a two-event mouse model of transfusion-related acute lung injury (mTRALI). We have now identified changes in HPs induced by UVB light and responses of the recipient animal that mediate the mTRALI. STUDY DESIGN AND METHODS: Effects of UVB on HPs were monitored by flow cytometry and aggregation. HPs exposed to UVB, with or without inhibitors to specific biochemical pathways, were infused into lipopolysaccharide (LPS)-primed severe combined immunodeficient (SCID) mice. ALI was monitored by protein elevations in bronchoalveolar lavage fluid (BALF). RESULTS: UVB increased fibrinogen binding and potentiated HP aggregation. Infusion of UVB HPs into LPS-primed SCID mice led to macrophage inflammatory protein 2 (MIP-2) elevations in plasma and BALF and resulted in ALI. Protein kinase C (PKC) inhibitors prevented UVB-induced HP changes in vitro and reduced MIP-2 elevation and mTRALI in vivo. Blocking of fibrinogen binding to HP αIIbß3 with c7E3 monoclonal antibody prevented mTRALI. MIP-2 elevation in vivo in response to UVB HPs was essential for ALI since blocking of MIP-2 receptor in vivo prevented mTRALI. CONCLUSION: PKC signaling mediates UVB-induced HP fibrinogen binding and aggregation in vitro. The host animal responds to an infusion of UVB HPs by MIP-2 elevation that mediates downstream mTRALI. Elucidation of molecular mechanisms in UVB HP-mediated mTRALI may provide insight into pulmonary adverse events reported with UV-irradiated pathogen-reduced platelets.

Host platelets and, in part, neutrophils mediate lung accumulation of transfused UVB-irradiated human platelets in a mouse model of acute lung injury.

We previously reported that ultraviolet light B (UVB)-treated human platelets (hPLTs) can cause acute lung injury (ALI) in a two-event SCID mouse model in which the predisposing event was Lipopolysaccharide (LPS) injection and the second event was infusion of UVB-treated hPLTs. To delineate contributions of host mouse platelets (mPLTs) and neutrophils in the pathogenesis of ALI in this mouse model, we depleted mPLTs or neutrophils and measured hPLT accumulation in the lung. We also assessed lung injury by protein content in bronchoalveolar lavage fluid (BALF). LPS injection followed by infusion of UVB-treated hPLTs resulted in sequestration of both mPLTs and hPLTs in the lungs of SCID mice, although the numbers of neutrophils in the lung were not significantly different from the control group. Depletion of mouse neutrophils caused only a mild reduction in UVB-hPLTs accumulation in the lungs and a mild reduction in protein content in BALF. In comparison, depletion of mPLTs almost completely abolished hPLTs accumulation in the lung and significantly reduced protein content in BALF. UVB-treated hPLTs bound to host mPLTs, but did not bind to neutrophils in the lung. Aspirin treatment of hPLTs in vitro abolished hPLT accumulation in the lung and protected mice from lung injury. Our data indicate that host mPLTs accumulated in the lungs in response to an inflammatory challenge and subsequently mediated the attachment of transfused UVB-hPLTs. Neutrophils also recruited a small percentage of platelets to the lung. These findings may help develop therapeutic strategies for ALI which could potentially result from transfusion of UV illuminated platelets.

Immunohistochemical staining of dpERK staining during early kidney development.

Signaling through the ERK/MAPK pathway within the Wolffian duct and ureteric bud epithelium is critical for kidney induction and branching morphogenesis. ERK signaling is activated by receptor tyrosine kinase such as RET and FGFR2. This protocol describes a method to detect the diphosphorylated form of ERK (dpERK) on paraffin embedded tissue of early mouse embryo.

FGF8 is essential for formation of the ductal system in the male reproductive tract.

During development of the urogenital tract, fibroblast growth factor 8 (Fgf8) is expressed in mesonephric tubules, but its role in this tissue remains undefined. An evaluation of previously generated T-Cre-mediated Fgf8-deficient mice (T-Cre; Fgf8(flox/Δ2,3) mice), which lack Fgf8 expression in the mesoderm, revealed that the cranial region of the Wolffian duct degenerated prematurely and the cranial mesonephric tubules were missing. As a result, the epididymis, vas deferens and efferent ductules were largely absent in mutant mice. Rarb2-Cre was used to eliminate FGF8 from the mesonephric tubules but to allow expression in the adjacent somites. These mutants retained the cranial end of the Wolffian duct and formed the epididymis and vas deferens, but failed to elaborate the efferent ductules, indicating that Fgf8 expression by the mesonephric tubules is required specifically for the formation of the ductules. Ret knockout mice do not form the ureteric bud, a caudal outgrowth of the Wolffian duct and progenitor for the collecting duct network in the kidney, but they do develop the cranial end normally. This indicates that Fgf8, but not Ret, expression is essential to the outgrowth of the cranial mesonephric tubules from the Wolffian duct and to the development of major portions of the sex accessory tissues in the male reproductive tract. Mechanistically, FGF8 functions upstream of Lhx1 expression in forming the nephron, and analysis of Fgf8 mutants similarly shows deficient Lhx1 expression in the mesonephric tubules. These results demonstrate a multifocal requirement for FGF8 in establishing the male reproductive tract ducts and implicate Lhx1 signaling in tubule elongation.

Dissection of embryonic mouse kidney, culture in vitro, and imaging of the developing organ.

INTRODUCTION: In this article, we outline procedures for the dissection of intact kidneys and the isolation of the ureteric bud (UB) and the metanephric mesenchyme (MM) from mouse embryos. The apparatus required for the culture of these tissues in vitro is described in detail as well as the equipment necessary for performing time-lapse imaging studies of the developing kidney.