Reactive Molecular Dynamics Simulation on Degradation of Tetracycline Antibiotics Treated by Cold Atmospheric Plasmas.

The abuse of tetracycline antibiotics (TCs) has caused serious environmental pollution and risks to public health. Degradation of TCs by cold atmospheric plasmas (CAPs) is a high efficiency, low energy consumption and environmentally friendly method. In this study, a reactive molecular dynamics (MD) simulation is applied to study the interactions of reactive oxygen species (ROS) produced in CAPs and TCs (including tetracycline (TC), oxytetracycline (OTC), chlortetracycline (CTC) and demeclocycline (DMC)). As revealed by the simulation data at the atomic level, the main reaction sites on TCs are the C2 acylamino, the C4 dimethylamine, the C6 methyl group, the C8 site on the benzene ring and the C12a tertiary alcohol. The interaction between ROS and TCs is usually initiated by H-abstraction, followed by the breaking and formation of the crucial chemical bonds, such as the breaking of C-C bonds, C-N bonds and C-O bonds and the formation of C=C bonds and C=O bonds. Due to the different structures of TCs, when the ROS impact OTC, CTC and DMC, some specific reactions are observed, including carbonylation at the C5 site, dechlorination at the C7 site and carbonylation at the C6 site, respectively. Some degradation products obtained from the simulation data have been observed in the experimental measurements. In addition, the dose effects of CAP on TCs by adjusting the number of ROS in the simulation box are also investigated and are consistent with experimental observation. This study explains in detail the interaction mechanisms of degradation of TCs treated by CAPs with the final products after degradation, provides theoretical support for the experimental observation, then suggests optimization to further improve the efficiency of degradation of TCs by CAPs in applications.

Performance enhancement of an N-polar nitride deep-ultraviolet light-emitting diode with compositionally graded p-AlGaN.

Highly efficient hole injection into a AlGaN quantum well is desirable in nitride deep-ultraviolet light-emitting diodes (DUV LEDs) for high optical performance. In this work, we report the observation of enhanced hole injection in the N-polar AlGaN-based DUV LEDs with compositionally graded p-AlxGa1-xN (x = 0.65-0.75) by simulation and show that the enhanced hole injection leads to the increase of the peak internal quantum efficiency (IQE) and the significant reduction of efficiency droop at high current density. This work might activate researchers to realize the efficient polarization p-type doping of N-polar AlGaN with high Al content and thus to achieve high performance DUV LEDs experimentally.

Performance enhancement of nitrogen-polar GaN-based light-emitting diodes prepared by metalorganic chemical vapor deposition.

Nitrogen-polar (N-polar) III-nitride materials have great potential for application in long-wavelength light-emitting diodes (LEDs). However, the poor quality of N-polar nitride materials hinders the development of N-polar devices. In this work, we report the enhanced performance of N-polar GaN-based LEDs with an optimized InGaN/GaN double quantum well (DQW) structure grown by metalorganic chemical vapor deposition. We improved the quality of the N-polar InGaN/GaN DQWs by elevating the growth temperature and introducing hydrogen as the carrier gas during the growth of the quantum barrier layers. N-polar LEDs prepared based on the optimized InGaN/GaN DQWs show significantly enhanced (by over 90%) external quantum efficiency and a weakened droop effect compared with a reference LED. More importantly, the optimized N-polar DQWs show a significantly longer emission wavelength than Ga-polar DQWs grown at the same QW growth temperature. This work provides a feasible approach to improving the quality of the N-polar InGaN/GaN QW structure, and it will promote the development of N-polar GaN-based long-wavelength light-emitting devices for micro-LED displays.

The miRNA-15b/USP7/KDM6B axis engages in the initiation of osteoporosis by modulating osteoblast differentiation and autophagy.

Osteoporosis is a metabolic disease that results from oxidative stress or inflammation in renal disorders. microRNAs (miRNAs) are recently implicated to participate in osteoporosis, but the mechanism remains largely unexplored. Herein, we aimed to explore the potential role of miR-15b in osteoblast differentiation and autophagy in osteoporosis. We established osteoporosis models through ovariectomy and determined that miR-15b was highly expressed whereas USP7 and KDM6B were poorly expressed in tissue of osteoporosis mice. Treatment of silenced miR-15b resulted in the elevation of decreased bone mineral density (BMD), the maximum elastic stress and the maximum load of osteoporosis mice. In osteoblasts, miR-15 overexpression decreased proliferation but suppressed the cell differentiation and autophagy, accompanied with decreased expression of USP7. Mechanistically, miR-15 bound and inhibited USP7 expression, while overexpression of USP7 promoted autophagy of osteoblasts. USP7, importantly, strengthened the stability of KDM6B and promoted KDM6B expression. MG132 protease inhibitor increased KDM6B and USP7 expression in osteoblasts. Silencing of KDM6B reversed the promoting effect on autophagy and proliferation induced by overexpression of USP7. Taken altogether, miR-15b inhibits osteoblast differentiation and autophagy to aggravate osteoporosis by targeting USP7 to regulate KDM6B expression.

Plasma-induced destruction of Candida albicans cell wall components: A reactive molecular dynamics simulation.

Cold atmospheric plasma (CAP) has attracted significant attention and has been widely used to inactivate pathogens based on its excellent effect; however, the mechanisms underlying the interactions between plasma-generated species and organisms have not yet been fully elucidated. In this paper, the interactions of reactive oxygen plasma species (O, OH and H2O2) with chitin polymer (the skeletal component of the Candida albicans cell wall) were investigated by means of reactive molecular dynamics simulations from a microscopic point of view. Our simulations show that O and OH species can break important structural bonds (e.g., N-H bonds, O-H bonds and C-H bonds) of chitin. This is followed by a cascade of bond cleavage and double bond formation events. This simulation study aimed to improve the understanding of the micromechanism of plasma-inactivated Candida albicans at the atomic level.

Accurate Monitoring Platform for the Surface Catalysis of Nanozyme Validated by Surface-Enhanced Raman-Kinetics Model.

Surface-enhanced Raman scattering (SERS) is a supersensitive technique for monitoring catalytic reactions. However, building a SERS-kinetics model to investigate catalytic efficiency on the surface or interface of the catalyst remains a great challenge. In the present study, we successfully obtained an excellent semiconducting SERS substrate, reduced MnCo2O4 (R-MnCo2O4) nanotubes, whose favorable SERS sensitivity is mainly related to the promoted interfacial charge transfer caused by the introduction of oxygen vacancies as well as the electromagnetic enhancement effect. Furthermore, the R-MnCo2O4 nanotubes showed a favorable oxidase-like activity toward oxidation with the aid of molecular oxygen. It was also showed the oxidase-like catalytic process could be monitored using the SERS technique. A new SERS-kinetics model to monitor the catalytic efficiency of the oxidase-like reaction was developed, and the results demonstrate that the Vm values measured by the SERS-kinetics method are close to that obtained by the UV-vis approach, while the Km values measured by the SERS-kinetics method are much lower, demonstrating the better affinity between the enzyme and the substrate from SERS results and further confirming the high sensitivity of the SERS-kinetics approach and the actual enzyme-like reaction on the surface of nanozymes, which provides guidance in understanding the kinetics process and catalytic mechanism of natural enzymatic and other artificial enzymatic reactions. This work demonstrated the improved SERS sensitivity of defective semiconductors for the application of enzyme mimicking, providing a new frontier to construct highly sensitive biosensors.

Anomalous electroluminescent blue-shift behavior induced by well widths variance and localization effect in InGaN/GaN multi-quantum wells.

Twelve InGaN MQW LED samples with varying well thickness grown via metal-organic chemical vaper deposition (MOCVD) are investigated. It is observed from electroluminescence (EL) measurement that at low current densities, the peak energy shifts to blue with increasing current, and when the current change by fixed increment, the peak energy shifts to blue end to different extent among samples. This blue shift was expected to be stronger when the well thickness increases, however, for well widths above 5 nm we observe a decrease in emission energy. Since no relaxation was detected from reciprocal space mapping (RSM), the deteriorated homogeneity is found to be responsible for this phenomenon. Temperature dependent photoluminescence (TDPL) results analyzed by band-tail model fitting show that the localization effect gets more prominent with increasing well thickness. It is found that elevating the growth temperature of active region from 710°C to 750°C significantly improves the homogeneity of InGaN layer.

Effect of carrier transfer process between two kinds of localized potential traps on the spectral properties of InGaN/GaN multiple quantum wells.

Two InGaN/GaN multiple-quantum-well (MQW) samples with identical epitaxial structures are grown at different growth rates via metal-organic chemical vapor deposition system. The room temperature photoluminescence intensity of the fast-grown sample is much stronger than that of the slow-grown one. In addition, the fast-grown sample has two luminescence peaks at low temperatures, and the height of main peak anomalously increases with increasing temperature below 100 K. Such improved emission efficiency and the untypical temperature-induced increase of peak height can be attributed to the carrier's transferring between two kinds of localized traps with different potential depth in the fast-grown sample, where the distribution of indium is seriously inhomogeneous. The enhanced fluctuation of indium is caused by the reduced migration time of adsorbed atoms due to the increased growth rate during the epitaxial growth of MQW region.

Investigation of growth parameters influence on self-catalyzed ITO nanowires by high RF-power sputtering.

ITO nanowires have been successfully fabricated using a radio-frequency sputtering technique with a high RF-power of 250W. The fabrication of the ITO nanowires has been optimized through the study of oxygen flow rates, temperatures and RF-power. The difference in the morphology of the ITO nanowires prepared by using a new target and a used target has been first observed and the mechanism for the difference has been discussed in detail. A hollow structure and air voids within the nanowires are formed during the process of the nanowire growth. The ITO nanowires fabricated by this method has demonstrated good conductivity (15Ω/sq) and a transmittance of more than 64% at a wavelength longer than 550nm after annealing. Furthermore, detailed microstructure studies show that the ITO nanowires exhibit a large number of oxygen vacancies. As a result, it is expected that they can be useful for the fabrication of gas sensor devices.

High-Efficiency and Air-Stable Perovskite Quantum Dots Light-Emitting Diodes with an All-Inorganic Heterostructure.

Perovskite light-emitting diodes (PeLEDs), because of its fundamental scientific importance and practical applications in the fields of low-cost light source or display applications, have drawn worldwide attention in recent years. However, PeLEDs available today suffer from a compromise in their emission efficiency and operation stability. In this study, we designed and fabricated a stacking all-inorganic multilayer structure by using inorganic perovskite CsPbBr3 quantum dots (QDs) as the emissive layer and inorganic n-type MgZnO and p-type MgNiO as the carrier injectors, respectively. Through energy band engineering of carrier injectors by Mg incorporation and their thickness optimization, PeLEDs with maximum luminance of 3809 cd/m2, luminous efficiency of 2.25 cd/A, and external quantum efficiency of 2.39% have been realized, which are much better than most PeLEDs from CH3NH3PbBr3 films, and comparable with the highest results reported on CsPbBr3 QDs LEDs. More importantly, the unencapsulated PeLEDs in a continuous current mode demonstrate a remarkable operation stability against water and oxygen degradation. After a continuous operation for 10 h under a dc bias (10.0 V), nearly 80% of the original efficiency of the PeLEDs has been retained, greatly superior to reference and other previously reported devices constructed with conventional organic carrier injectors. Our results obtained open possibilities for the design and development of high-efficiency and air-stable PeLEDs that are not dependent on expensive and less-stable organic carrier injectors.

Exciton localization and ultralow onset ultraviolet emission in ZnO nanopencils-based heterojunction diodes.

n-GaN/i-ZnO/p-GaN double heterojunction diodes were constructed by vertically binding p-GaN wafer on the tip of ZnO nanopencil arrays grown on n-GaN/sapphire substrates. An increased quantum confinement in the tip of ZnO nanopencils has been verified by photoluminescence measurements combined with quantitative analyses. Under forward bias, a sharp ultraviolet emission at ~375 nm due to localized excitons recombination can be observed in ZnO. The electroluminescence mechanism of the studied diode is tentatively elucidated using a simplified quantum confinement model. Additionally, the improved performance of the studied diode featuring an ultralow emission onset, a good operation stability and an enhanced ultraviolet emission shows the potential of our approach. This work provides a new route for the design and development of ZnO-based excitonic optoelectronic devices.

Electrically pumped ultraviolet lasing in polygonal hollow microresonators: investigation on optical cavity effect.

Electrically driven ultraviolet lasing was realized in two-dimensional ZnO nanowall networks from Au/MgO/n-ZnO/n-GaN/In structure, and whispering gallery type resonant modes are responsible for the lasing action. We present a comparative study on lasing action based on nanowall networks with different micro-hole sizes. The representative diode (Device II) with a moderate micro-hole size exhibits an ultralow threshold current density of 1.01 A/cm2, and the lasing action can be sustained at a temperature up to ∼413 K, showing a good temperature tolerance. Moreover, the corresponding characteristic temperature for Device II was derived as ∼91.4 K. It can be qualitatively anticipated that this work will provide instructive guidelines for fabrication and development of high-performance ultraviolet laser diodes by using two-dimensional ZnO nanowall networks as the lasing gain media.

The growth of ZnO on stainless steel foils by MOCVD and its application in light emitting devices.

Direct fabrication of semiconductor light emitting devices on metal foils is beneficial, because it brings flexibility and good heat sink in the devices. In this work, we have grown ZnO on the commercially available stainless steel foils by metal-organic chemical vapor deposition for the first time. With the increase of growth temperature, the morphology changes from a thin film structure to closely stacked columns, and eventually to nanorods. The change in the migration ability of adatoms due to the increase of growth temperature plays an important role in the evolution of morphology. The samples with nanorod morphology exhibit relatively better crystallinity and optical quality. A PEDOT: PSS/PMMA/ZnO device was fabricated based on the grown ZnO nanorods. The metal-insulator-semiconductor type device shows an uncommon symmetric I-V curve. Under reverse bias, the device emits fairly pure UV light, which comes from the near band edge emission of ZnO. The working mechanism of the devices has been discussed, and a model mainly based on the Poole-Frenkel effect is proposed to describe the charge transportation of the devices.

MicroRNA-145 Suppresses Osteosarcoma Metastasis via Targeting MMP16.

BACKGROUND: Metastasis is a leading cause of mortality for osteosarcoma (OS) patients, and its molecular pathological mechanisms remain to be elucidated. Previous studies have suggested a significant role of microRNAs (miRNAs) in the control of cancel cell migration and invasion. METHODS: Real-time PCR was used to screen the differentially expressed miRNAs between OS with or without metastasis, and miR-145 underexpression was observed in metastatic OS. Luciferase assay was performed to validate the target gene. RESULTS: Further, we identified three genes, MMP16, ADAM17 and metadherin, as possible targets of miR-145. We identified MMP16 as a target gene of miR-145 and ruled out ADAM17 and metadherin as targets in OS using a dual luciferase reporter system. Subsequently, we determined and compared the expression level of MMP16 in human OS samples and showed that the mRNA and protein levels of MMP16 were significantly up-regulated in primary OS with metastasis compared with those without metastasis. We also altered miR-145 expression by transfecting OS cells with miR-145 mimics or inhibitors. MMP16 expression was similarly downregulated in the cells transfected with miR-145 mimics or MMP16-specific siRNA, and the invasive and migratory capability of those cells was significantly suppressed compared with negative controls. MMP16 expression was consistently significantly upregulated in the cells transfected with miR-145 inhibitors, and the invasive and migratory capability of those cells was significantly promoted compared with negative controls. Conclcusion: Our results suggest that miR-145 functions as a tumor metastasis suppressor gene by down-regulating MMP16 and may be a potential target in osteosarcoma treatment.

Brain protection conferred by long-term administration of 2-(2-benzofuranyl)-2-imidazoline against experimental autoimmune encephalomyelitis.

Our previous studies showed that 2-(2-benzofuranyl)-2-imidazoline (2-BFI), a ligand to type 2 imidazoline receptor, was protective against brain and spinal cord injury caused by experimental autoimmune encephalomyelitis (EAE). In the present study, we investigated the effect of long-term administration of 2-BFI and the dose-dependent response relationship of long-term administration of 2-BFI with neuroprotection. Treatment with 2-BFI at doses of 5, 10, and 20 mg/kg for 14 days significantly reduced hind limb paralysis and the severity of EAE compared with the EAE control group. Long-term use of 2-BFI was not only safe to mice, but also dose-dependently reduced the expression of inflammatory cytokines, including TNF-α, Interferon-γ and Interleukin-17A, compared with the EAE control group. Expressions of neuronal injury markers, including cytochrome c, AIF and ß-APP, were also reduced significantly in response to long-term 2-BFI treatment. Together, these results provided new evidence to demonstrate that 2-BFI is a safe and effective candidate for further development as a therapeutic drug for treatment of multiple sclerosis.

Photoluminescence performance enhancement of ZnO/MgO heterostructured nanowires and their applications in ultraviolet laser diodes.

Vertically aligned ZnO/MgO coaxial nanowire (NW) arrays were prepared on sapphire substrates by metal-organic chemical vapor deposition combined with a sputtering system. We present a comparative investigation of the morphological and optical properties of the produced heterostructures with different MgO layer thicknesses. Photoluminescence measurements showed that the optical performances of ZnO/MgO coaxial NWs were strongly dependent on the MgO layer thickness. The intensity of deep-level emission (DLE) decreased monotonously with the increase of MgO thickness, while the enhancement of ultraviolet (UV) emission showed a critical thickness of 15 nm, achieving a maximum intensity ratio (∼226) of IUV/IDLE at the same time. The significantly improved exciton emission efficiency of the coaxial NW structures allows us to study the surface passivation effect, photogenerated carrier confinement and transfer in terms of energy band theory. More importantly, we achieved an ultralow threshold (4.5 mA, 0.58 A cm(-2)) electrically driven UV lasing action based on the ZnO/MgO NW structures by constructing an Au/MgO/ZnO metal/insulator/semiconductor diode, and the continuous-current-driven diode shows a good temperature tolerance. The results obtained on the unique optical properties of ZnO/MgO coaxial NWs shed light on the design and development of ZnO-based UV laser diodes assembled with nanoscale building blocks.

Molecular dynamics simulation of the transmembrane transport process of reactive species under the synergistic effect of plasma oxidation and an electric field.

Cold atmospheric pressure plasma (CAP)-assisted cancer therapy has become a popular topic in plasma biomedical research. Membrane lipid oxidation and local electric fields are two important factors in plasma-cell interactions, and the study of their synergistic effect is highly significant for optimizing the regulatory mechanism of the plasma-induced apoptosis of cancer cells. In this paper, a model of oxidized phospholipids was established, and the transmembrane process of reactive species was simulated by the classical molecular dynamics (MD) method under the conditions of oxidation and an electric field. The results showed that hydrophilic reactive oxygen species could not penetrate the membrane lipids through oxidation. The formation of electroporation provided a new channel for reactive species to penetrate the membrane, and the oxidation effect reduced the electric field threshold of membrane electroporation. Our simulation could provide theoretical support for the plasma-induced apoptosis of cancer cells at the microscopic level, provide mechanistic guidance for the practical application of plasma-induced cancer therapy, and promote the development of CAP in the field of cancer therapy.

Effects of Nitro-Oxidative Stress on Biomolecules: Part 1-Non-Reactive Molecular Dynamics Simulations.

Plasma medicine, or the biomedical application of cold atmospheric plasma (CAP), is an expanding field within plasma research. CAP has demonstrated remarkable versatility in diverse biological applications, including cancer treatment, wound healing, microorganism inactivation, and skin disease therapy. However, the precise mechanisms underlying the effects of CAP remain incompletely understood. The therapeutic effects of CAP are largely attributed to the generation of reactive oxygen and nitrogen species (RONS), which play a crucial role in the biological responses induced by CAP. Specifically, RONS produced during CAP treatment have the ability to chemically modify cell membranes and membrane proteins, causing nitro-oxidative stress, thereby leading to changes in membrane permeability and disruption of cellular processes. To gain atomic-level insights into these interactions, non-reactive molecular dynamics (MD) simulations have emerged as a valuable tool. These simulations facilitate the examination of larger-scale system dynamics, including protein-protein and protein-membrane interactions. In this comprehensive review, we focus on the applications of non-reactive MD simulations in studying the effects of CAP on cellular components and interactions at the atomic level, providing a detailed overview of the potential of CAP in medicine. We also review the results of other MD studies that are not related to plasma medicine but explore the effects of nitro-oxidative stress on cellular components and are therefore important for a broader understanding of the underlying processes.

Reproduction of a fossil rhinoceros from 18 mya and origin of litter size in perissodactyls.

Reproductive strategy is among the most important characteristics of organism. Here, we report reproductive strategy of singleton pregnancy of a fossil rhinoceros, Plesiaceratherium gracile, from 18 mya of the Shanwang Basin, China. Dental and body development data revealed that after birth, the calf of P. gracile is breastfed for 2-3 years; at approximately 5 years of age, when the M2 tooth is slightly worn, the female has already reached sexual maturity and attained a size close to that of an adult and could give birth to the first calf. Furthermore, given litter size is phylogenetically conservative and closely correlates with body size, we conclude that the litter size of perissodactyls is determined by the singleton pregnancy since the Eocene. By contrast, other reproductive traits are highly variable and have a different pace of evolution, and traits observed in living rhinoceroses have been evolving at least since 18 mya.

The crosslink between the hyaluronic acid and drugs treated by reactive oxygen species produced in plasma based on the molecular dynamics simulation.

Hyaluronic Acid (HA)-based pre-drugs can enable targeted drug delivery to cancer cells with CD44-high expressing, thus, it is essential to design an efficient, target specific drug delivery system based on HA. Plasma, as a simple and clean tool, has been widely used in the modification and crosslinking of biological materials in recent years. In this paper, we used the Reactive Molecular Dynamic (RMD) to explore the reaction between reactive oxygen species (ROS) in plasma and HA with drugs (PTX, SN-38, and DOX), in order to examine possible drug-coupled systems. The simulation results indicated the acetylamino groups in HA could be oxidized to unsaturated acyl groups, which offers the possibility of crosslinking. Three drugs also exposed the unsaturated atoms under the impact of ROS, which can cross-link directly to HA through CO and CN bonds, forming a drug coupling system with better release. This study revealed the exposure of active sites on HA and drugs by ROS impact in plasma, allowing us to study the crosslinking mechanism between HA and drugs at molecular level deeply, and also provided a new light for establishment of HA-based targeted drug delivery system.