Therapeutic delivery of CCL2 modulates immune response and restores host-microbe homeostasis.

Many chronic inflammatory diseases are attributed to disturbances in host-microbe interactions, which drive immune-mediated tissue damage. Depending on the anatomic setting, a chronic inflammatory disease can exert unique local and systemic influences, which provide an exceptional opportunity for understanding disease mechanism and testing therapeutic interventions. The oral cavity is an easily accessible environment that allows for protective interventions aiming at modulating the immune response to control disease processes driven by a breakdown of host-microbe homeostasis. Periodontal disease (PD) is a prevalent condition in which quantitative and qualitative changes of the oral microbiota (dysbiosis) trigger nonresolving chronic inflammation, progressive bone loss, and ultimately tooth loss. Here, we demonstrate the therapeutic benefit of local sustained delivery of the myeloid-recruiting chemokine (C-C motif) ligand 2 (CCL2) in murine ligature-induced PD using clinically relevant models as a preventive, interventional, or reparative therapy. Local delivery of CCL2 into the periodontium inhibited bone loss and accelerated bone gain that could be ascribed to reduced osteoclasts numbers. CCL2 treatment up-regulated M2-macrophage and downregulated proinflammatory and pro-osteoclastic markers. Furthermore, single-cell ribonucleic acid (RNA) sequencing indicated that CCL2 therapy reversed disease-associated transcriptomic profiles of murine gingival macrophages via inhibiting the triggering receptor expressed on myeloid cells-1 (TREM-1) signaling in classically activated macrophages and inducing protein kinase A (PKA) signaling in infiltrating macrophages. Finally, 16S ribosomal ribonucleic acid (rRNA) sequencing showed mitigation of microbial dysbiosis in the periodontium that correlated with a reduction in microbial load in CCL2-treated mice. This study reveals a novel protective effect of CCL2 local delivery in PD as a model for chronic inflammatory diseases caused by a disturbance in host-microbe homeostasis.

Interaction of magnolia bark extracts with Staphylococcus aureus DNA and evaluation of the stability of their antibacterial activities.

Magnolia bark is an edible traditional Chinese medicine that has antibacterial activity against Staphylococcus aureus. In the present study, interactions between S. aureus DNA and raw magnolia bark (RMB) and ginger mix-fried magnolia bark (GMB) aqueous extracts were determined via spectroscopic methods. Fluorescence spectroscopy and Stern-Volmer constants showed that S. aureus DNA quenched the fluorescence of the extracts by static quenching. UV-Vis spectroscopy and iodide quenching experiments indicated that the interactions between S. aureus DNA and the fluorescent substances might involve groove binding or electrostatic interactions. In 4', 6-diamidino-2-phenylindole competitive assays, the fluorescence intensity at decreased as the extract amount was increased. This indicates that groove binding is responsible for the fluorescence quenching. The antibacterial activity of GMB aqueous extract treated under light, cold, heat and cycling hot-cold conditions decreased by 13.99, 9.31, 10.89 and 14.40%, respectively, whereas that of RMB aqueous extract treated under the same conditions decreased by 8.91, 14.99, 14.99 and 13.70%, respectively. The results indicate that S. aureus DNA quenches the fluorescence of GMB and RMB aqueous extracts by grooving interactions. Additionally, the antibacterial activities of GMB and RMB extracts are sensitive to light and temperature, respectively.

Establishment of 2D Crystal Heterostructures by Sulfurization of Sequential Transition Metal Depositions: Preparation, Characterization, and Selective Growth.

A nine-layer WS2/MoS2 heterostructure is established on a sapphire substrate after sequential growth of large-area and uniform five- and four-layer MoS2 and WS2 films by using sulfurization of predeposited 1.0 nm molybdenum (Mo) and tungsten (W), respectively. By using the results obtained from the ultraviolet photoelectron spectroscopy and the absorption spectrum measurements of the standalone MoS2 and WS2 samples, a type-II band alignment is predicated for the WS2/MoS2 heterostructure. Increasing drain currents and enhanced field-effect mobility value of the transistor fabricated on the heterostructure suggested that a channel with higher electron concentration compared with the standalone MoS2 transistor channel is obtained with electron injection from WS2 to MoS2 under thermal equilibrium. Selective 2D crystal growth with (I) blank sapphire substrate, (II) standalone MoS2, (III) WS2/MoS2 heterostructure, and (IV) standalone WS2 was demonstrated on a single sapphire substrate. The results have revealed the potential of this growth technique for practical applications.

Cystic Fibrosis: Understanding Cystic Fibrosis Transmembrane Regulator Mutation Classification and Modulator Therapies.

A common life-threatening hereditary disease, Cystic Fibrosis (CF), affects primarily Caucasian infants. High sweat-salt levels are observed as a result of a single autosomal mutation in chromosome 7 that affects the critical function of the cystic fibrosis transmembrane regulator (CFTR). For establishing tailored treatment strategies, it is important to understand the broad range of CFTR mutations and their impacts on disease pathophysiology. This study thoroughly investigates the six main classes of classification of CFTR mutations based on their functional effects. Each class is distinguished by distinct molecular flaws, such as poor protein synthesis, misfolding, gating defects, conduction defects, and decreased CFTR expression at the apical membrane. Furthermore, this paper focuses on the emerging field of CFTR modulators, which intend to restore CFTR function or mitigate its consequences. These modulators, which are characterized by the mode of action and targeted mutation class, have the potential to provide personalized therapy regimens in CF patients. This review provides valuable insights into the genetic basis of CF pathology, and highlights the potential for precision medicine methods in CF therapy by thoroughly investigating CFTR mutation classification and related modulators.

Hole Injection Effect and Dynamic Characteristic Analysis of Normally Off p-GaN HEMT with AlGaN Cap Layer on Low-Resistivity SiC Substrate.

A p-GaN HEMT with an AlGaN cap layer was grown on a low resistance SiC substrate. The AlGaN cap layer had a wide band gap which can effectively suppress hole injection and improve gate reliability. In addition, we selected a 0° angle and low resistance SiC substrate which not only substantially reduced the number of lattice dislocation defects caused by the heterogeneous junction but also greatly reduced the overall cost. The device exhibited a favorable gate voltage swing of 18.5 V (@IGS = 1 mA/mm) and an off-state breakdown voltage of 763 V. The device dynamic characteristics and hole injection behavior were analyzed using a pulse measurement system, and Ron was found to increase and VTH to shift under the gate lag effect.

Improved Ion/Ioff Current Ratio and Dynamic Resistance of a p-GaN High-Electron-Mobility Transistor Using an Al0.5GaN Etch-Stop Layer.

In this study, we investigated enhance mode (E-mode) p-GaN/AlGaN/GaN high-electron-mobility transistors (HEMTs) with an Al0.5GaN etch-stop layer. Compared with an AlN etch-stop layer, the Al0.5GaN etch-stop layer not only reduced lattice defects but engendered improved DC performance in the device; this can be attributed to the lattice match between the layer and substrate. The results revealed that the Al0.5GaN etch-stop layer could reduce dislocation by 37.5% and improve device characteristics. Compared with the device with the AlN etch-stop layer, the p-GaN HEMT with the Al0.5GaN etch-stop layer achieved a higher drain current on/off ratio (2.47 × 107), a lower gate leakage current (1.55 × 10-5 A/mm), and a lower on-state resistance (21.65 Ω·mm); moreover, its dynamic RON value was reduced to 1.69 (from 2.26).

Optimization of the Field Plate Design of a 1200 V p-GaN Power High-Electron-Mobility Transistor.

This study optimized the field plate (FP) design (i.e., the number and positions of FP layers) of p-GaN power high-electron-mobility transistors (HEMTs) on the basic of simulations conducted using the technology computer-aided design software of Silvaco. Devices with zero, two, and three FP layers were designed. The FP layers of the HEMTs dispersed the electric field between the gate and drain regions. The device with two FP layers exhibited a high off-state breakdown voltage of 1549 V because of the long distance between its first FP layer and the channel. The devices were subjected to high-temperature reverse bias and high-temperature gate bias measurements to examine their characteristics, which satisfied the reliability specifications of JEDEC.

Characteristic Analysis of AlGaN/GaN HEMT with Composited Buffer Layer on High-Heat Dissipation Poly-AlN Substrates.

In this study, an AlGaN/GaN high-electron-mobility transistor (HEMT) was grown through metal organic chemical vapor deposition on a Qromis Substrate Technology (QST). The GaN on the QST device exhibited a superior heat dissipation performance to the GaN on a Si device because of the higher thermal conductivity of the QST substrate. Thermal imaging analysis indicated that the temperature variation of the GaN on the QST device was 4.5 °C and that of the GaN on the Si device was 9.2 °C at a drain-to-source current (IDS) of 300 mA/mm following 50 s of operation. Compared with the GaN HEMT on the Si device, the GaN on the QST device exhibited a lower IDS degradation at high temperatures (17.5% at 400 K). The QST substrate is suitable for employment in different temperature environments because of its high thermal stability.

High Thermal Dissipation of Normally off p-GaN Gate AlGaN/GaN HEMTs on 6-Inch N-Doped Low-Resistivity SiC Substrate.

Efficient heat removal through the substrate is required in high-power operation of AlGaN/GaN high-electron-mobility transistors (HEMTs). Thus, a SiC substrate was used due to its popularity. This article reports the electrical characteristics of normally off p-GaN gate AlGaN/GaN high-electron-mobility transistors (HEMTs) on a low-resistivity SiC substrate compared with the traditional Si substrate. The p-GaN HEMTs on the SiC substrate possess several advantages, including electrical characteristics and good qualities of epitaxial crystals, especially on temperature performance. Additionally, the price of the low-resistivity SiC substrate is three times lower than the ordinary SiC substrate.

Normally-Off p-GaN Gated AlGaN/GaN MIS-HEMTs with ALD-Grown Al2O3/AlN Composite Gate Insulator.

A metal-insulator-semiconductor p-type GaN gate high-electron-mobility transistor (MIS-HEMT) with an Al2O3/AlN gate insulator layer deposited through atomic layer deposition was investigated. A favorable interface was observed between the selected insulator, atomic layer deposition-grown AlN, and GaN. A conventional p-type enhancement-mode GaN device without an Al2O3/AlN layer, known as a Schottky gate (SG) p-GaN HEMT, was also fabricated for comparison. Because of the presence of the Al2O3/AlN layer, the gate leakage and threshold voltage of the MIS-HEMT improved more than those of the SG-HEMT did. Additionally, a high turn-on voltage was obtained. The MIS-HEMT was shown to be reliable with a long lifetime. Hence, growing a high-quality Al2O3/AlN layer in an HEMT can help realize a high-performance enhancement-mode transistor with high stability, a large gate swing region, and high reliability.

[Measurement of exhaled volatile organic compounds in lung cancer patients].

OBJECTIVE: to study the characteristics of volatile organic compounds (VOCs) in exhaled breath of lung cancer patients, and therefore to explore its use in the diagnosis of the disease. METHODS: from February 2007 to September 2009, 55 patients with lung cancer, 21 patients with benign lung diseases and 30 healthy controls were enrolled in our study. The VOCs in exhaled breath were detected by the SPME (solid phase microextraction)-GC (gas chromatography) system. RESULTS: heptanal was detected in 45 patients of the lung cancer group, 1 of the benign lung disease group, and 1 of the healthy control group. The positive rate was higher in the lung cancer group as compared to the benign lung disease group and the healthy group combined (P < 0.05). The detection of heptanal was not related to age, smoking, histological type and staging (P > 0.05). CONCLUSION: heptanal maybe a useful marker in VOCs from patients with lung cancer.

Effect of expertise on TF adaptive system instrumentation quality in simulated mandibular molar canals.

The aim of the study was to examine the effect of operator experience on the quality of instrumentation of molar canals using the TF Adaptive file system (SybronEndo, Orange, CA) on a 3D-printed molar replica model. Three novice and two expert operators instrumented the root canals of three replicas each and resulting pre- and postinstrumentation 12 micron voxel size-microCT volumes of each replica were digitally registered. Relative modified canal wall surface fraction and canal transportation (1-9 mm from the apex) were calculated and analysed by anova. Instrumentation by expert operators resulted in overall higher (P = 0.002) modified wall surface fraction in the distal but not the mesial and higher (P = 0.002) combined from all canal level transportation in the mesiobuccal canals but not the mesiolingual and distal canals. Instrumentation efficiency but also transportation using the TF Adaptive file system can be higher among expert, compared to novice, operators, depending on the canal type.

In vivo study of self-assembled alkylsilane coated degradable magnesium devices.

Magnesium (Mg) and its alloys are candidate materials for resorbable implantable devices, such as orthopedic devices or cardiovascular stents. Mg has a number advantages, including mechanical properties, light weight, its osteogenic effects and the fact that its degradation products are nontoxic and naturally present in the body. However, production of H2 gas during the corrosion reaction can cause formation of gas pockets at the implantation site, posing a barrier to clinical applications of Mg. It is therefore desirable to develop methods to control corrosion rate and gas pocket formation around the implants. Here we evaluate the potential of self-assembled multilayer alkylsilane (AS) coatings to control Mg device corrosion and formation of gas pockets in vivo and to assess effects of the AS coatings on the surrounding tissues in a subcutaneous mouse model over a 6 weeks' period. The coating significantly slowed down corrosion and gas pocket formation as evidenced by smaller gas pockets around the AS coated implants (ANOVA; p = 0.013) and decrease in the weight loss values (t test; p = 0.07). Importantly, the microCT and profilometry analyses demonstrated that the coating inhibited the pitting corrosion. Specifically, the roughness of the coated samples was ∼30% lower than uncoated specimen (p = 0.02). Histological assessment of the tissues under the implant revealed no inflammation or foreign body reaction. Overall, our results demonstrate the feasibility of use of the seld assembled AS coatings for reduction of gas pocket formation around the resorbable Mg devices. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 342-351, 2019.

Controlling magnesium corrosion and degradation-regulating mineralization using matrix GLA protein.

Magnesium (Mg) alloys are embraced for their biodegradability and biocompatibility. However, Mg degrades spontaneously in the biological environment in vivo and in vitro, triggering deposition of calcium phosphate on the metal. Upon complete metal absorption, minerals remain in the tissue, which could lead to pathogenic calcification. Hence, our aims are to test the feasibility of matrix GLA protein (MGP) to locally inhibit Mg mineralization that is induced by metal alloy degradation. MGP is a small secretory protein that has been shown to inhibit soft tissue calcification. We exposed Mg to MGP, stably transfected into mammalian cells. Results showed that less calcium and phosphorous deposition on the Mg surface when MGP was present relative to when it was not. In the in vivo mouse intramuscular model conducted for 4 and 6 weeks, Mg rods were embedded in collagen scaffolds, seeded with cells overexpressing MGP. Microtomography, electron dispersive x-ray spectroscopy, and histology assessments revealed lower deposited mineral volume around Mg rods from the MGP group. Compared to other groups, higher volume loss after implantation was observed from the MGP group at both time points, indicating a higher corrosion rate without the protective mineral layer. This study is the first to our knowledge to demonstrate that local exposure to a biomolecule, such as MGP, can modulate the corrosion of Mg-based implants. These findings may have important implications for the future design of endovascular stents and orthopedic devices.

Large-Area and Strain-Reduced Two-Dimensional Molybdenum Disulfide Monolayer Emitters on a Three-Dimensional Substrate.

Atomically thin membranes of two-dimensional (2-D) transition-metal dichalcogenides (TMDCs) have distinct emission properties, which can be utilized for realizing ultrathin optoelectronic integrated systems in the future. Growing a large-area and strain-reduced monolayer 2-D material on a three-dimensional (3-D) substrate with microstructures or nanostructures is a crucial technique because the electronic band structure of TMDC atomic layers is strongly affected by the number of stacked layers and strain. In this study, a large-area and strain-reduced MoS2 monolayer was fabricated on a 3-D substrate through a two-step growth procedure. The material characteristics and optical properties of monolayer TMDCs fabricated on the nonplanar substrate were examined. The growth of monolayer MoS2 on a cone-shaped sapphire substrate effectively reduced the tensile strain induced by the substrate by decreasing the thermal expansion mismatch between the 2-D material and the substrate. Monolayer MoS2 grown on the nonplanar substrate exhibited uniform strain reduction and luminescence intensity. The fabrication of monolayer MoS2 on a nonplanar substrate increased the light extraction efficiency. In the future, large-area and strain-reduced 2-D TMDC materials grown on a nonplanar substrate can be employed as novel light-emitting devices for applications in lighting, communication, and displays for the development of ultrathin optoelectronic integrated systems.

Single-Crystal Antimonene Films Prepared by Molecular Beam Epitaxy: Selective Growth and Contact Resistance Reduction of the 2D Material Heterostructure.

Single-crystal antimonene flakes are observed on sapphire substrates after the postgrowth annealing procedure of amorphous antimony (Sb) droplets prepared by using molecular beam epitaxy at room temperature. The large wetting angles of the antimonene flakes to the sapphire substrate suggest that an alternate substrate should be adopted to obtain a continuous antimonene film. By using a bilayer MoS2/sapphire sample as the new substrate, a continuous and single-crystal antimonene film is obtained at a low growth temperature of 200 °C. The results are consistent with the theoretical prediction of the lower interface energy between antimonene and MoS2. The different interface energies of antimonene between sapphire and MoS2 surfaces lead to the selective growth of antimonene only atop MoS2 surfaces on a prepatterned MoS2/sapphire substrate. With similar sheet resistance to graphene, it is possible to use antimonene as the contact metal of 2D material devices. Compared with Au/Ti electrodes, a specific contact resistance reduction up to 3 orders of magnitude is observed by using the multilayer antimonene as the contact metal to MoS2. The lower contact resistance, the lower growth temperature, and the preferential growth to other 2D materials have made antimonene a promising candidate as the contact metal for 2D material devices.

MicroCT analysis of vascular morphometry: a comparison of right lung lobes in the SUGEN/hypoxic rat model of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a rare disease characterized by significant vascular remodeling within the lung. Clinical computed tomography (CT) scans are routinely used to aid in PAH diagnosis. Animal models, including the Sugen-hypoxic rat model (SU/hyp), of PAH closely mimic human PAH development. We have previously used micro-computed tomography (microCT) to find extensive right lung vascular remodeling in the SU/hyp. We hypothesized that the individual right lung lobes may not contribute equally to overall lung vascular remodeling. Sprague-Dawley rats were subjected to a subcutaneous injection of vascular endothelial growth factor receptor blocker (Sugen 5416) and subsequently exposed to chronic hypoxic conditions (10% O2) for three weeks. Following perfusion of the lung vasculature with an opaque resin (Microfil), the right lung lobes were microCT-imaged with a 10-µm voxel resolution and 3D morphometry analysis was performed separately on each lobe. As expected, we found a significantly lower ratio of vascular volume to total lobe volume in the SU/hyp compared with the control, but only in the distal lobes (inferior: 0.23 [0.21-0.30] versus 0.35 [0.27-0.43], P = 0.02; accessory: 0.27 [0.25-0.33] versus 0.37 [0.29-0.43], P = 0.06). Overall, we observed significantly fewer continuous blood vessels and reduced vascular density while having greater vascular lumen diameters in the distal lobes of both groups ( P < 0.05). In addition, the vascular separation within the SU/hyp lobes and the vascular surface area to volume ratio were significantly greater in the SU/hyp lobes compared with controls ( P < 0.03). Results for the examined parameters support the overall extensive vascular remodeling in the SU/hyp model and suggest this may be lobe-dependent.

The Growth Mechanism of Transition Metal Dichalcogenides by using Sulfurization of Pre-deposited Transition Metals and the 2D Crystal Hetero-structure Establishment.

A growth model is proposed for the large-area and uniform MoS2 film grown by using sulfurization of pre-deposited Mo films on sapphire substrates. During the sulfurization procedure, the competition between the two mechanisms of the Mo oxide segregation to form small clusters and the sulfurization reaction to form planar MoS2 film is determined by the amount of background sulfur. Small Mo oxide clusters are observed under the sulfur deficient condition, while large-area and complete MoS2 films are obtained under the sulfur sufficient condition. Precise layer number controllability is also achieved by controlling the pre-deposited Mo film thicknesses. The drain currents in positive dependence on the layer numbers of the MoS2 transistors with 1-, 3- and 5- layer MoS2 have demonstrated small variation in material characteristics between each MoS2 layer prepared by using this growth technique. By sequential transition metal deposition and sulfurization procedures, a WS2/MoS2/WS2 double hetero-structure is demonstrated. Large-area growth, layer number controllability and the possibility of hetero-structure establishment by using sequential metal deposition and following sulfurization procedures have revealed the potential of this growth technique for practical applications.

Preparation of Large-area Vertical 2D Crystal Hetero-structures Through the Sulfurization of Transition Metal Films for Device Fabrication.

We have demonstrated that through the sulfurization of transition metal films such as molybdenum (Mo) and tungsten (W), large-area and uniform transition metal dichalcogenides (TMDs) MoS2 and WS2 can be prepared on sapphire substrates. By controlling the metal film thicknesses, good layer number controllability, down to a single layer of TMDs, can be obtained using this growth technique. Based on the results obtained from the Mo film sulfurized under the sulfur deficient condition, there are two mechanisms of (a) planar MoS2 growth and (b) Mo oxide segregation observed during the sulfurization procedure. When the background sulfur is sufficient, planar TMD growth is the dominant growth mechanism, which will result in a uniform MoS2 film after the sulfurization procedure. If the background sulfur is deficient, Mo oxide segregation will be the dominant growth mechanism at the initial stage of the sulfurization procedure. In this case, the sample with Mo oxide clusters covered with few-layer MoS2 will be obtained. After sequential Mo deposition/sulfurization and W deposition/sulfurization procedures, vertical WS2/MoS2 hetero-structures are established using this growth technique. Raman peaks corresponding to WS2 and MoS2, respectively, and the identical layer number of the hetero-structure with the summation of individual 2D materials have confirmed the successful establishment of the vertical 2D crystal hetero-structure. After transferring the WS2/MoS2 film onto a SiO2/Si substrate with pre-patterned source/drain electrodes, a bottom-gate transistor is fabricated. Compared with the transistor with only MoS2 channels, the higher drain currents of the device with the WS2/MoS2 hetero-structure have exhibited that with the introduction of 2D crystal hetero-structures, superior device performance can be obtained. The results have revealed the potential of this growth technique for the practical application of 2D crystals.

Serum Endothelial Cell-Specific Molecule 1 (Endocan) Levels in Patients With Acute Myocardial Infarction and Its Clinical Significance.

Endothelial dysfunction is involved in the process of acute myocardial infarction (AMI), that is, the endothelial cell-specific molecule 1 (ESM-1; endocan) is a novel endothelial dysfunction marker. However, the relationship between patients with AMI and serum ESM-1 levels is not very clear. Patients with AMI (n = 216) and a control group (n = 60) without AMI were included in the study. High-sensitivity C-reactive protein (hsCRP) was measured, and the severity of AMI was assessed by a modified Gensini stenosis scoring system. Serum ESM-1 levels were significantly higher in the AMI group ( P < .05). High-sensitivity C-reactive protein levels were also significantly higher in the AMI group ( P < .05). In patients with AMI, serum ESM-1 levels were not significantly correlated with hsCRP levels. There was no significant correlation between serum ESM-1 level and Gensini score. Our findings suggest that serum ESM-1 levels may be a novel biomarker of endothelial dysfunction in patients with AMI.