Edwardsiella tarda induces airways inflammation and production of autoantibodies against lung tissues through regulation of the IL-33-ST2 axis.

Chronic obstructive pulmonary disease (COPD) is a highly prevalent chronic respiratory disease characterised by irreversible airways obstruction associated with chronic airways inflammation and remodelling, while the pathogenesis and the mechanistic differences between patients remain to be fully elucidated. We previously reported that alarmin cytokine IL-33 may contribute to the production of autoantibodies against respiratory epithelial cells. Here we expand the hypothesis that pulmonary autoimmune responses induced by airway microbiota also contribute to the progression of COPD. We focused on Edwardsiella tarda which we detected uniquely in the induced sputum of patients with acute exacerbations of COPD. Pernasal challenge of the airways of WT mice with supernatants of cultured E. tarda induced marked, elevated expression of IL-33 in the lung tissues. Immunisation of animals with supernatants of cultured E. tarda resulted in significantly elevated airways inflammation, the formation of tertiary lymphatic structures and significantly elevated proportions of T follicular helper T cells in the lung tissue and mediastinal lymph nodes. Interestingly, such challenge also induced production of IgG autoantibodies directed against lung tissue lysate, alveolar epithelial cell proteins and elastin fragment, while putrescine, one of metabolites generated by the bacterium, might play an important role in the autoantibody production. Furthermore, all of these effects were partly but significantly abrogated in mice with deletion of the IL-33 receptor ST2. Collectively, these data support the hypothesis that COPD is progressed at least partly by airways microbiota such as E. tarda initiating autoimmune attack of the airways epithelium mediated at least partly through the IL-33-ST2 axis.

Low-Temperature Thermal Transport Characteristics in Epitaxial Bilayer Graphene Microbridges.

In this paper, we present a study of the thermal transport of epitaxial bilayer graphene microbridges. The thermal conductance of three graphene microbridges with different lengths was measured at different temperatures using Johnson noise thermometry. We find that with the decrease of the temperature, the thermal transport in the graphene microbridges switches from electron-phonon coupling to electron diffusion, and the switching temperature is dependent on the length of the microbridge, which is in good agreement with the simulation based on a distributed hot-spot model. Moreover, the electron-phonon thermal conductance has a temperature power law of T3 as predicted for pristine graphene and the electron-phonon coupling coefficient σep is found to be approximately 0.18 W/(m2 K4), corresponding to a deformation potential D of 55 eV. In addition, the electron diffusion in the graphene microbridges adheres to the Wiedemann-Franz law, requiring no corrections to the Lorentz number.

A method to improve positioning of denture teeth on denture bases for CAD-CAM complete dentures: A dental technique.

In the digital workflow of complete denture fabrication, one solution for producing computer-aided design and computer-aided manufacturing dentures has been to mill the denture teeth and base separately and then bond them together. The correct bonding of the denture teeth and base is important to reproduce the designed occlusion in the definitive prosthesis. A novel technique is described to assist in the accurate positioning of denture teeth on the denture base by constructing auxiliary positioning slots on the denture base and auxiliary positioning posts on the denture teeth. The technique can assist in accurately assembling CAD-CAM milled complete dentures and may shorten chairside time by reducing clinical occlusal adjustment.

Demonstration of a 263-GHz Traveling Wave Tube for Electron Paramagnetic Resonance Spectroscopy.

In this letter, a 263 GHz traveling wave tube for electron paramagnetic resonance spectroscopy is designed, fabricated and tested. A periodic permanent magnet focused pencil beam electron optical system is adopted. A folded waveguide slow-wave structure with modified serpentine bends is optimized to provide high-power wideband performance and stable operation. An experiment has been performed to verify the analysis results and confirm the amplifier stability. The device provides a maximum 11.9 W saturation output power and 25.5 dB saturation gain. Although the available solid-state signal source is unable to drive the amplifier to saturation beyond 260 - 264 GHz, 10 W output power over 5.6 GHz bandwidth has been measured.

Chitosan/Hyaluronic Acid/MicroRNA-21 Nanoparticle-Coated Smooth Titanium Surfaces Promote the Functionality of Human Gingival Fibroblasts.

Purpose: Forming a compact biological seal between the gingiva and the implant interface around the percutaneous parts of an implant is one of the key issues in preventing peri-implantitis. Methods: In this study, since microRNA-21 (miR-21) has been approved to promote fibroblast proliferation and collagen formation in skin fibrosis, we prepared miR-21-loaded chitosan (CS)/tripolyphosphate (TPP)/hyaluronic acid (HA) nanoparticles (CTH NPs) and cross-linked them to smooth Ti surfaces with 0.2% gel solution for reverse transfection, after which isolated human gingival fibroblasts were cultured on the miR-21-functionalized Ti substrates. Results: An optimal CS:TPP:HA ratio (1:0.15:0.1) and N/P ratio (20:1) were chosen to produce appropriate nanoparticles. Finally, the CTH/miR-21 nanoparticle-coated smooth Ti surfaces demonstrated increased fibroblast adhesion, proliferation and expression of extracellular matrix-related genes along with similar cytotoxicity and cell spreading on the miR-21-functionalized Ti surface and the unmodified smooth Ti surface. Conclusion: The chitosan-based nanoparticles might be an efficient nonviral miRNA vector to form a stable biological seal in percutaneous areas of Ti for clinical use.

α1-Antitrypsin Binds to the Glucocorticoid Receptor with Anti-Inflammatory and Antimycobacterial Significance in Macrophages.

α1-Antitrypsin (AAT), a serine protease inhibitor, is the third most abundant protein in plasma. Although the best-known function of AAT is irreversible inhibition of elastase, AAT is an acute-phase reactant and is increasingly recognized to have a panoply of other functions, including as an anti-inflammatory mediator and a host-protective molecule against various pathogens. Although a canonical receptor for AAT has not been identified, AAT can be internalized into the cytoplasm and is known to affect gene regulation. Because AAT has anti-inflammatory properties, we examined whether AAT binds the cytoplasmic glucocorticoid receptor (GR) in human macrophages. We report the finding that AAT binds to GR using several approaches, including coimmunoprecipitation, mass spectrometry, and microscale thermophoresis. We also performed in silico molecular modeling and found that binding between AAT and GR has a plausible stereochemical basis. The significance of this interaction in macrophages is evinced by AAT inhibition of LPS-induced NF-κB activation and IL-8 production as well as AAT induction of angiopoietin-like 4 protein, which are, in part, dependent on GR. Furthermore, this AAT-GR interaction contributes to a host-protective role against mycobacteria in macrophages. In summary, this study identifies a new mechanism for the gene regulation, anti-inflammatory, and host-defense properties of AAT.

Finite Element Study of PEEK Materials Applied in Post-Retained Restorations.

BACKGROUND: This study aimed to investigate the biomechanical behaviors of polyether ether ketone (PEEK) and traditional materials (titanium and fiber) when used to restore tooth defects in the form of prefabricated post or customized post via computational modelling. METHODS: First, the prototype of natural tooth, and the prototypes of prefabricated post and customized post were established, respectively, whilst the residual root was restored with dentin ferrule using reverse engineering methods. Then, the stress and strain of CFR-PEEK (PEEK reinforced by 30% carbon fiber) and pure PEEK (PEEK without any reprocessing) post were compared with those made in traditional materials using the three-dimensional finite element method. RESULTS: From the stress point of view, compared with metal and fiber posts, CFR-PEEK and pure PEEK prefabricated post both demonstrated reduced post-core interface stress, post stress, post-root cement stress and root cement stress; moreover, CFR-PEEK and pure PEEK customized post demonstrated reduced post stress, post-root cement stress and root cement stress, while the strain of CFR-PEEK post was the closest to that of dentin. CONCLUSIONS: Compared with the traditional posts, both the CFR-PEEK and pure PEEK posts could reduce the risk of debonding and vertical root fracture, whether they were used as prefabricated posts or customized posts, but the biomechanical behavior of carbon fiber-reinforced CFR-PEEK restorations was the closest to dentin, no matter if they were used as prefabricated post or customized post. Therefore, the CFR-PEEK post could be more suitable to restore massive tooth defects. Pure PEEK needs filler reinforcement to be used for post-retained restoration.

Comprehensively Improved Performance of ß-Ga2O3 Solar-Blind Photodetector Enabled by a Homojunction with Unique Passivation Mechanisms.

Ga2O3-based solar-blind photodetectors have been extensively investigated for a wide range of applications. However, to date, a lot of research has focused on optimizing the epitaxial technique or constructing a heterojunction, and studies concerning surface passivation, a key technique in electronic and optoelectronic devices, are severely lacking. Here, we report an ultrasensitive metal-semiconductor-metal photodetector employing a ß-Ga2O3 homojunction structure realized by low-energy surface fluorine plasma treatment, in which an ultrathin fluorine-doped layer served for surface passivation. Without inserting/capping a foreign layer, this strategy utilized fluorine dopants to both passivate local oxygen vacancies and suppress surface chemisorption. The dual effects have opposite impacts on device current magnitude (by suppressing metal/semiconductor junction leakage and inhibiting surface-chemisorption-induced carrier consumption) but dominate in dark and under illumination, respectively. By means of such unique mechanisms, the simultaneous improvement on dark and photo current characteristics was achieved, leading to the sensitivity enhanced by nearly 1 order of magnitude. Accordingly, the 15 min treated sample exhibited striking competitiveness in terms of comprehensive properties, including a dark current as low as 6 pA, a responsivity of 18.43 A/W, an external quantum efficiency approaching 1 × 104%, a specific detectivity of 2.48 × 1014 Jones, and a solar-blind/UV rejection ratio close to 1 × 105. Furthermore, the response speed was effectively accelerated because of the reduction on metal/semiconductor interface trap states. Our findings provide a facile, economical, and contamination-free surface passivation technique, which unlocks the potential for comprehensively improving the performance of ß-Ga2O3 solar-blind metal-semiconductor-metal photodetectors.

128-pixel arrays of 4H-SiC UV APD with dual-frequency PECVD SiNx passivation.

In this paper, high-performance 1×128 linear arrays of 4H-SiC ultraviolet (UV) avalanche photodiode (APD) with dual-frequency plasma enhanced chemical vapor deposition (PECVD) passivation are demonstrated for the first time. The results show that SiNx dielectric deposited by dual-frequency PECVD can effectively reduce the leakage current at high bias voltages. Due to the improved 4H-SiC epi-layer material and SiNx passivation, the fabricated 22 mm-long 1×128 4H-SiC APD linear arrays exhibit an excellent performance with a high pixel yield of 100% and a small breakdown voltage variation of 0.2 V, which is the best result ever reported. At room temperature, the pixels have a gain of over 105 and a maximum quantum efficiency of 53.5% @ 285 nm. Besides the high uniformity of breakdown voltage for 128 pixels, the dark currents at 95% of breakdown voltage are all below 1 nA.

Ultra-extraordinary optical transmission induced by cascade coupling of surface plasmon polaritons in composite graphene-dielectric stack.

Surface plasmon polaritons have been extensively studied owing to the promising characteristics of near fields. In this paper, the cascade coupling of graphene surface plasmon polaritons (GSPPs) originating from cascading excitation and multiple coupling within a composite graphene-dielectric stack is presented. GSPPs confined to graphene layers are distributed in the entire stack as waveguide modes. Owing to the near-field enhancement effect and large lifetime of the GSPPs, the terahertz wave-graphene interaction is significantly enhanced, which induces an ultra-extraordinary optical transmission (UEOT) together with the reported negative dynamic conductivity of graphene. Furthermore, owing to cascade coupling, the UEOT exhibits considerable transmission enhancement, up to three orders of magnitude, and frequency and angle selections. Based on the key characteristics of cascade coupling, the mode density and coupling intensity of GSPPs, the dependences of the number of graphene layers in the stack, the thickness of dielectric buffers, and the effective Fermi levels of the graphene on the UEOT are also analyzed. The proposed mechanism can pave the way for using layered plasmonic materials in electric devices, such as amplifiers, sensors, detectors, and modulators.

Differential Responses by Human Macrophages to Infection With Mycobacterium tuberculosis and Non-tuberculous Mycobacteria.

Mycobacterium tuberculosis (MTB) and non-tuberculous mycobacteria (NTM) are formidable causes of lung diseases throughout the world. While MTB is considered to be more virulent than NTM, host factors also play a key role in disease development. To elucidate whether there are differential immune responses to various mycobacteria, THP-1 macrophages were temporally infected with MTB H37Rv or with four different NTM species. We found that cells infected with MTB had greater bacterial burden and p65 nuclear factor-kappa B (NF-κB) activation than cells infected with NTM. There was also differential expression of mRNA for interleukin-1-ß (IL-1ß), IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α) with no distinct pattern of mRNA expression among the different mycobacteria. In contrast, at the protein level, some generalizations can be made of the cytokines and chemokines expressed. Compared to uninfected cells, the rapid-growing Mycobacterium smegmatis but not Mycobacterium abscessus induced significantly greater pro-inflammatory cytokines and IL-10, whereas both NTM individually induced greater levels of chemokines. Compared to uninfected control cells, the two slow-growing NTM and MTB differentially induced cytokine expression with Mycobacterium avium inducing more pro-inflammatory cytokines and IL-10, whereas M. avium, Mycobacterium intracellulare, and MTB inducing greater but similar levels of chemokines. MTB-infected THP-1 cells also demonstrated lower level of phagosome-lysosome fusion and apoptosis than NTM-infected cells while there were differences in these macrophage functions among the NTM species. Interestingly, M. intracellulare, M. avium, and MTB have similar levels of autophagosome formation, but the levels displayed by all three were lower than for M. smegmatis and M. abscessus. This study demonstrates the differences in bacterial burden and macrophage effector functions among several clinically relevant mycobacterial species. Such disparities may, in part, account for differences in clinical outcomes among patients infected with various species of NTM as has been seen for different strains of MTB.

High-Speed Efficient Terahertz Modulation Based on Tunable Collective-Individual State Conversion within an Active 3 nm Two-Dimensional Electron Gas Metasurface.

Terahertz (THz) modulators are always realized by dynamically manipulating the conversion between different resonant modes within a single unit cell of an active metasurface. In this Letter, to achieve real high-speed THz modulation, we present a staggered netlike two-dimensional electron gas (2DEG) nanostructure composite metasurface that has two states: a collective state with massive surface resonant characteristics and an individual state with meta-atom resonant characteristics. By controlling the electron transport of the nanoscale 2DEG with an electrical grid, collective-individual state conversion can be realized in this composite metasurface. Unlike traditional resonant mode conversion confined in meta-units, this state conversion enables the resonant modes to be flexibly distributed throughout the metasurface, leading to a frequency shift of nearly 99% in both the simulated and experimental transmission spectra. Moreover, such a mechanism can effectively suppress parasitic modes and significantly reduce the capacitance of the metasurface. Thereby, this composite metasurface can efficiently control the transmission characteristics of THz waves with high-speed modulations. As a result, 93% modulation depth is observed in the static experiment and modulated sinusoidal signals up to 3 GHz are achieved in the dynamic experiment, while the -3 dB bandwidth can reach up to 1 GHz. This tunable collective-individual state conversion may have great application potential in wireless communication and coded imaging.

Three-Dimensionally-Printed Polyether-Ether-Ketone Implant with a Cross-Linked Structure and Acid-Etched Microporous Surface Promotes Integration with Soft Tissue.

Polyether-ether-ketone (peek) is one of the most common materials used for load-bearing orthopedic devices owing to its radiolucency and favorable mechanical properties. However, current smooth-surfaced peek implants can lead to fibrous capsule formation. To overcome this issue, here, peek specimens with well-defined internal cross-linked structures (macropore diameters of 1.0-2.0 mm) were fabricated using a three-dimensional (3D) printer, and an acid-etched microporous surface was achieved using injection-molding technology. The cell adhesion properties of smooth and microporous peek specimens was compared in vitro through a scanning electron microscope (SEM), and the soft tissue responses to the both microporous and cross-linked structure of different groups were determined in vivo using a New Zealand white rabbit model, and examined through histologic staining and separating test. The results showed that the acid-etched microporous surface promoted human skin fibroblasts (HSF) adherence, while internal cross-linked structure improved the ability of the peek specimen to form a mechanical combination with soft tissue, especially with the 1.5 mm porous specimen. The peek specimens with both the internal cross-linked structure and external acid-etched microporous surface could effectively promote the close integration of soft tissue and prevent formation of fibrous capsules, demonstrating the potential for clinical application in surgical repair.

Alpha-1-Antitrypsin Enhances Primary Human Macrophage Immunity Against Non-tuberculous Mycobacteria.

Rationale: The association between non-tuberculous mycobacterial lung disease and alpha-1-antitrypsin (AAT) deficiency is likely due, in part, to underlying emphysema or bronchiectasis. But there is increasing evidence that AAT itself enhances host immunity against microbial pathogens and thus deficiency could compromise host protection. Objectives: The goal of this project is to determine if AAT could augment macrophage activity against non-tuberculous mycobacteria. Methods: We compared the ability of monocyte-derived macrophages cultured in autologous plasma that were obtained immediately before and soon after AAT infusion-given to individuals with AAT deficiency-to control an ex vivo Mycobacterium intracellulare infection. Measurements and Main Results: We found that compared to pre-AAT infused monocyte-derived macrophages plus plasma, macrophages, and contemporaneous plasma obtained after a session of AAT infusion were significantly better able to control M. intracellulare infection; the reduced bacterial burden was linked with greater phagosome-lysosome fusion and increased autophagosome formation/maturation, the latter due to AAT inhibition of both M. intracellulare-induced nuclear factor-kappa B activation and A20 expression. While there was a modest increase in apoptosis in the M. intracellulare-infected post-AAT infused macrophages and plasma, inhibiting caspase-3 in THP-1 cells, monocyte-derived macrophages, and alveolar macrophages unexpectedly reduced the M. intracellulare burden, indicating that apoptosis impairs macrophage control of M. intracellulare and that the host protective effects of AAT occurred despite inducing apoptosis. Conclusion: AAT augments macrophage control of M. intracellulare infection through enhancing phagosome-lysosome fusion and autophagy.

miR-34a promotes bone regeneration in irradiated bone defects by enhancing osteoblastic differentiation of mesenchymal stromal cells in rats.

BACKGROUND: Radiation exposure negatively affects the regenerative ability and makes reconstruction of bone defects after tumor section difficult. miR-34a is involved in radiation biology and bone metabolism. The aim of this study was to investigate whether miR-34a could contribute to bone regeneration in irradiated bone defects. METHODS: The expression of miR-34a was analyzed during the osteoblastic differentiation of irradiated BMSCs and bone formation in irradiated bone defects. miR-34a mimics and miR-34a inhibitor were used to upregulate or suppress the expression of miR-34a in BMSCs irradiated with 2 or 4 Gy X-ray radiation. In vitro osteogenesis and subcutaneous osteogenesis were used to assess the effects of miR-34a on the osteogenic ability of radiation-impaired BMSCs. Collagen-based hydrogel containing agomiR-34a or antagomiR-34a were placed into the 3-mm defects of irradiated rat tibias to test the effect of miR-34a on bone defect healing after irradiation. RESULTS: miR-34a was upregulated in the process of bone formation after irradiation. Transfecting radiation-impaired BMSCs with miR-34a mimics enhanced their osteoblastic differentiation in vitro by targeting NOTCH1. Overexpression of miR-34a enhanced the ectopic bone formation of irradiated BMSCs. In situ delivery of miR-34a promoted bone regeneration in irradiated bone defects. CONCLUSIONS: miR-34a promoted the osteoblastic differentiation of BMSCs and enhanced the ectopic bone formation after irradiation. miR-34a promoted bone defect healing in irradiated rat tibias. miR-34a-targeted therapy might be a promising strategy for promoting the reconstruction of bone defects after radiotherapy.

Wet Chemical Method for Black Phosphorus Thinning and Passivation.

Layered black phosphorus (BP) has been expected to be a promising material for future electronic and optoelectronic applications since its discovery. However, the difficulty in mass fabricating layered air-stable BP severely obstructs its potential industry applications. Here, we report a new BP chemical modification method to implement all-solution-based mass production of layered air-stable BP. This method uses the combination of two electron-deficient reagents 2,2,6,6-tetramethylpiperidinyl- N-oxyl (TEMPO) and triphenylcarbenium tetrafluorobor ([Ph3C]BF4) to accomplish thinning and/or passivation of BP in organic solvent. The field-effect transistor and photodetection devices constructed from the chemically modified BP flakes exhibit enhanced performances with environmental stability up to 4 months. A proof-of-concept BP thin-film transistor fabricated through the all-solution-based exfoliation and modification displays an air-stable and a typical p-type transistor behavior. This all-solution-based method improves the prospects of BP for industry applications.

Optimization Strategy of 4H-SiC Separated Absorption Charge and Multiplication Avalanche Photodiode Structure for High Ultraviolet Detection Efficiency.

In this work, parametric investigations on structural optimization are systematically made for 4H-SiC-based separated absorption charge and multiplication (SACM) avalanche ultraviolet photodiode (UV APD). According to our results, the breakdown voltage can be strongly affected by the thickness for the multiplication layer and the doping concentration for the charge control layer. The thickness for the n-type ohmic contact layer, the absorption layer, and the charge control layer can remarkably affect the light penetration depth, which correspondingly influences the number of photo-generated electron-hole pairs, and therefore the aforementioned layer thickness has a strong impact on the responsivity for SACM APD. For enhancing the responsivity of the APD, we require a reduced energy band barrier height at the interface of the optical absorption layer and the charge control layer, so that the promoted carrier transport into the multiplication layer can be favored. In addition, we investigate positive beveled mesas with smaller angles so as to reduce the electric field at the mesa edge. Thus, the dark current is correspondingly suppressed.

Growth of graphene with large single-crystal domains by Ni foam-assisted structure and its high-gain field-effect transistors.

High-quality graphene materials and high-performance graphene transistors have attracted much attention in recent years. To obtain high-performance graphene transistors, large single-crystal graphene is needed. The synthesis of large-domain-sized single-crystal graphene requires low nucleation density; this can lead to a lower growth rate. In this study, a Ni-foam assisted structure was developed to control the nucleation density and growth rate of graphene by tuning the flow dynamics. Lower nucleation density and high growth rate (∼50 µm min-1) were achieved with a 4 mm-gap Ni foam. With the graphene transistor fabrication process, a pre-deposited Au film as the protective layer was used during the graphene transfer. Graphene transistors showed good current saturation with drain differential conductance as low as 0.04 S mm-1 in the strong saturation region. For the devices with gate length of 2 µm, the intrinsic cut-off frequency f T and maximum oscillation frequency f max were 8.4 and 16.3 GHz, respectively, with f max/f T = 1.9 and power gain of up to 6.4 dB at 1 GHz. The electron velocity saturation induced by the surface optical phonons of SiO2 substrates was analyzed. Electron velocity saturation and ultra-thin Al2O3 gate dielectrics were thought to be the reasons for the good current saturation and high power gain of the graphene transistors.

Enhancing electronic and optoelectronic performances of tungsten diselenide by plasma treatment.

Transition metal dichalcogenides (TMDCs) have recently become spotlighted as nanomaterials for future electronic and optoelectronic devices. In this work, we develop an effective approach to enhance the electronic and optoelectronic performances of WSe2-based devices by N2O plasma treatment. The hole mobility and sheet density increase by 2 and 5 orders of magnitude, reaching 110 cm2 V-1 s-1 and 2.2 × 1012 cm-2, respectively, after the treatment. At the same time, the contact resistance (Rc) between WSe2 and its metal electrode drop by 5 orders of magnitude from 1.0 GΩ µm to 28.4 kΩ µm. The WSe2 photoconductor exhibits superior performance with high responsivity (1.5 × 105 A W-1), short response time (<2 ms), high detectivity (3.6 × 1013 Jones) and very large photoconductive gain (>106). We have also built a lateral p-n junction on a single piece of WSe2 flake by selective plasma exposure. The junction reaches an exceedingly high rectifying ratio of 106, an excellent photoresponsivity of 2.49 A W-1 and a fast response of 8 ms. The enhanced optoelectronic performance is attributed to band-engineering through the N2O plasma treatment, which can potentially serve as an effective and versatile approach for device engineering and optimization in a wide range of electronic and optoelectronic devices based on 2D materials.