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At least 1,531 records · Page 85

Exosomes secreted from mesenchymal stem cells mediate the regeneration of endothelial cells treated with rapamycin by delivering pro-angiogenic microRNAs

Highlights: • MSC-derived exosomes play an important role in promoting endothelial regeneration treated with rapamycin in vitro. • A distinct class of exosomal miRNAs is identified to be tightly related to endothelial regeneration. • The therapeutic effects of MSC-exosomes may be ascribed to the delivery of pro-angiogenic miRNAs to endothelial cells. • MSC-exosomes may serve as a cell-free therapy for clinical treatment of delayed endothelial healing after DES implantation. Delayed endothelial healing after drug eluting stent (DES) implantation is a critical clinical problem in treatment of coronary artery diseases. Exosomes exhibit proangiogenic potential in a variety of ischemic diseases. However, the association of exosomes with endothelial regeneration after DES implantation has been rarely reported. In this study, we aimed to investigate the therapeutic effects of mesenchymal stem cell (MSC)-derived exosomes on endothelial cells treated with rapamycin and explore the potential mechanisms of MSC-derived exosomes in promoting endothelial regeneration. Exosomes were isolated from MSCs by ultracentrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis, and Western blot assay. The in vitro effects of MSC-derived exosomes on the proliferation and migration of endothelial cells treated with rapamycin were evaluated by integrated experiment, cell counting kit-8, scratch, tube formation, and transwell assays. And the apoptosis of rapamycin-induced endothelial cells loaded with MSC-derived exosomes was detected using TUNEL and Annexin-V FITC and PI double-staining assays. The microRNA (miRNA) cargo of MSC-derived exosomes was identified by high-throughput RNA sequencing. Pro-angiogenic miRNAs and key pathways were further characterized. Our results indicated that MSC-derived exosomes could be ingested into umbilical vein endothelial cells (HUVECs) and significantly enhanced cell proliferation rate, migratory and tube-forming capabilities in vitro. MSC-derived exosomes also inhibited the apoptosis of HUVECs induced by rapamycin. A distinct class of exosomal miRNAs was further identified, including six miRNAs tightly related to neovasculogenesis. Silencing the expression of exosomal miRNA-21–5p and let-7c-5p attenuated the pro-proliferative and pro-migratory capacity of MSC-derived exosomes. Moreover, functional enrichment analysis indicated that metabolic pathways might contribute to reendothelialization. This study highlights a proregenerative effect of MSC-derived exosomes in vitro, which may be partly explained by the delivery of pro-angiogenic miRNAs to endothelial cells.

60 APPLIED LIFE SCIENCES↗

Radiation Damage Mechanisms in Oxide-Based Solid Electrolytes

Ion implantation is a promising approach to mitigate dendrite formation in metal anode solid-state batteries by modifying the chemical and mechanical properties of oxide-based electrolyte surfaces such as Li 7 La 3 Zr 2 O 12 (LLZO). Yet, the detailed atomistic mechanisms and potentially adverse side effects of ion implantation remain poorly understood. In this study, we used molecular dynamics simulations to elucidate the evolution of radiation-induced damage in LLZO. The results reveal that radiation damage is primarily driven by recoils from heavy ions in the lattice, producing antisite defect clusters whose density decreases as recoil energy increases, a counterintuitive finding that highlights complex cascade fragmentation. Radiation-induced disruption to the crystal sublattice connectivity, especially in the La–O network critical for Li-ion transport, leads to degradation in ionic pathways at low energies, while higher energy cascades can form new conduction pathways via enhanced Zr–O network connectivity. These findings provide a mechanistic foundation for optimizing ion implantation strategies that balance disruption of the lattice for surface modification for dendrite resistance with preservation of essential ionic conductivity.

Defects↗

Supramolecular Polymer Hydrogels for Drug-Induced Tissue Regeneration

Supramolecular polymers self-assemble into nanofibers, micelles, and other nanostructures through weak noncovalent interactions between subunits. Such systems possess attractive properties for use in a variety of practical settings such as energy, sustainability, and healthcare. In regenerative medicine, a common approach involves implanting a supramolecular material containing cell and growth factor binding motifs directly into a diseased or traumatized tissue defect, whereupon it interacts with and/or recruits components of the biological system to induce tissue healing. In this paper we introduce a supramolecular therapeutic in which tissue regeneration is orchestrated by a supramolecular polymer prodrug implanted subcutaneously in a remote tissue. Our approach exploits a hydrophobic small-molecule inhibitor of prolyl hydroxylase enzyme as both a regeneration-inducing therapeutic and a structure-directing agent in a supramolecular polymer that forms shear-thinning nanofiber hydrogels. Subcutaneous injection of the supramolecular hydrogel in the back of mice wounded with a critical-sized defect in the ear led to transient upregulation of hypoxia inducible factor-1α and regeneration of ear tissue in a manner reminiscent of epimorphic regeneration. This drug-induced regeneration strategy utilizes a simple and translatable supramolecular design, eliminates the need for delivery of biologics ( e. g., growth factors, cells), and avoids implantation of a foreign material directly in a tissue defect.

60 APPLIED LIFE SCIENCES↗

Laser activation of single group-IV colour centres in diamond

Abstract Spin-photon interfaces based on group-IV colour centres in diamond offer a promising platform for quantum networks. A key challenge in the field is realising precise single-defect positioning and activation, which is crucial for scalable device fabrication. Here we address this problem by demonstrating a two-step fabrication method for tin vacancy (SnV − ) centres that uses site-controlled ion implantation followed by local femtosecond laser annealing with in-situ spectral monitoring. The ion implantation is performed with sub-50 nm resolution and a dosage that is controlled from hundreds of ions down to single ions per site, limited by Poissonian statistics. Using this approach, we successfully demonstrate site-selective creation and modification of single SnV − centres. Our in-situ spectral monitoring opens a window onto materials tuning at the single defect level, and provides new insight into defect structures and dynamics during the annealing process. While demonstrated for SnV − centres, this versatile approach can be readily generalised to other implanted colour centres in diamond and wide-bandgap materials.

Science & Technology - Other Topics↗

A carbon nanotube reporter of microRNA hybridization events in vivo

MicroRNAs and other small oligonucleotides in biofluids are promising disease biomarkers, yet conventional assays require complex processing steps that are unsuitable for point-of-care testing or for implantable or wearable sensors. Single-walled carbon nanotubes are an ideal material for implantable sensors, owing to their emission in the near-infrared spectral region, photostability and exquisite sensitivity. In this, we report an engineered carbon-nanotube-based sensor capable of real-time optical quantification of hybridization events of microRNA and other oligonucleotides. The mechanism of the sensor arises from competitive effects between displacement of both oligonucleotide charge groups and water from the nanotube surface, which result in a solvatochromism-like response. The sensor, which allows for detection via single-molecule sensor elements and for multiplexing by using multiple nanotube chiralities, can monitor toehold-based strand-displacement events, which reverse the sensor response and regenerate the sensor complex. We also show that the sensor functions in whole urine and serum, and can non-invasively measure DNA and microRNA after implantation in live mice.

59 BASIC BIOLOGICAL SCIENCES↗

The Effect of an Externally Attached Neutrally Buoyant Transmitter on Mortal Injury during Simulated Hydroturbine Passage

On their seaward migration, juvenile salmonids commonly pass hydroelectric dams. Fish passing through hydroturbines experience a rapid decrease in pressure as they pass by the turbine blade and the severity of this decompression can be highly variable. This rapid decrease in pressure can result in injuries such as swim bladder rupture, exophthalmia, and emboli and hemorrhaging in the fins and tissues. However, recent research indicates that the presence of a telemetry tag (acoustic, radio, inductive) implanted inside the coelom of a juvenile salmon increases the likelihood that the fish will be injured or die during turbine passage. Thus, previous research conducted using telemetry tags implanted into the coelom of fish may have been inaccurate. Thus, a new technique is needed to provide unbiased estimates of survival through turbines. This research provides an evaluation of the effectiveness of a neutrally buoyant externally attached acoustic transmitter. Both nontagged fish and fish tagged with a neutrally buoyant external transmitter were exposed to a range of rapid decompressions simulating turbine passage. Juvenile Chinook salmon tagged with a neutrally buoyant externally attached acoustic transmitter did not receive a higher degree of barotrauma than their nontagged counterparts. We suggest that future research include field-based comparisons of survival and behavior among fish tagged with a neutrally buoyant external transmitter and those internally implanted with transmitters.

13 HYDRO ENERGY↗

Modeling surface backgrounds from radon progeny plate-out

The next generation low-background detectors operating deep underground aim for unprecedented low levels of radioactive backgrounds. The surface deposition and subsequent implantation of radon progeny in detector materials will be a source of energetic background events. We investigate Monte Carlo and model-based simulations to understand the surface implantation profile of radon progeny. Depending on the material and region of interest of a rare event search, these partial energy depositions can be problematic. Motivated by the use of Ge crystals for the detection of neutrinoless double-beta decay, we wish to understand the detector response of surface backgrounds from radon progeny. We look at the simulation of surface decays using a validated implantation distribution based on nuclear recoils and a realistic surface texture. Results of the simulations and measured α spectra are presented.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

The multi-scattering model for calculations of positron spatial distribution in the multilayer stacks, useful for conventional positron measurements

The spatial distribution of positrons emitted from radioactive isotopes into stacks or layered samples is a subject of the presented report. It was found that Monte Carlo (MC) simulations using GEANT4 code are not able to describe correctly the experimental data of the positron fractions in stacks. The mathematical model was proposed for calculations of the implantation profile or positron fractions in separated layers or foils being components of a stack. The model takes into account only two processes, i.e., the positron absorption and backscattering at interfaces. The mathematical formulas were applied in the computer program called LYS-1 (layers profile analysis). The theoretical predictions of the model were in the good agreement with the results of the MC simulations for the semi infinite sample. The experimental verifications of the model were performed on the symmetrical and non-symmetrical stacks of different foils. The good agreement between the experimental and calculated fractions of positrons in components of a stack was achieved. Also the experimental implantation profile obtained using the depth scanning of positron implantation technique is very well described by the theoretical profile obtained within the proposed model. The LYS-1 program allows us also to calculate the fraction of positrons which annihilate in the source, which can be useful in the positron spectroscopy.

97 MATHEMATICS AND COMPUTING↗

The E3 center in zinc oxide: Evidence for involvement of hydrogen

Proton implantation is shown to increase the concentration of the so called and commonly observed E3 defect level in zinc oxide (ZnO). Box and single profiles of protons with doses ranging from 6×10{sup 10} cm{sup −2} to 4.3×10{sup 12} cm{sup −2} were implanted into hydrothermally grown ZnO samples with original concentrations of E3 below 5×10{sup 14} cm{sup −3}. Capacitance-Voltage profiling and junction spectroscopy measurements showed that the charge carrier concentration and absolute concentration of E3 centers increase by more than one order of magnitude compared to the as-grown samples as well as control samples implanted with He ions. The results provide strong evidence for the involvement of H in the formation of the E3 center, and a complex involving interstitial H and an oxygen sub-lattice primary defect are discussed.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Site specific isolated nanostructure array formation on a large area by broad ion beam without any mask and resist

We report the formation of isolated nanostructure arrays on a large area via broad ion beam implantation without the aid of any mask or resist. Desired ions have been implanted at specific locations of the prefabricated silicon ripple or triangular structures by exploiting the variation of local ion impact angles. We have shown that the implantation of Fe ions on an O{sup +} ions induced pre fabricated triangular shaped patterned Si surface results in a self-organized periodic array of striped magnetic nanostructures having several micron length and about 50 nm width arranged with a spacial separation of ∼200 nm. The morphology, composition, crystalline structure, and magnetic property of these nanopatterns have been analyzed using high-resolution cross-sectional transmission electron microscopy and atomic force microscopy. A geometrical model has been proposed to explain the fundamental features of such ion-induced nanopattern structures.

77 NANOSCIENCE AND NANOTECHNOLOGY↗

The electroluminescence mechanism of Er³⁺ in different silicon oxide and silicon nitride environments

Rare earth doped metal-oxide-semiconductor (MOS) structures are of great interest for Si-based light emission. However, several physical limitations make it difficult to achieve the performance of light emitters based on compound semiconductors. To address this point, in this work the electroluminescence (EL) excitation and quenching mechanism of Er-implanted MOS structures with different designs of the dielectric stack are investigated. The devices usually consist of an injection layer made of SiO₂ and an Er-implanted layer made of SiO₂, Si-rich SiO₂, silicon nitride, or Si-rich silicon nitride. All structures implanted with Er show intense EL around 1540 nm with EL power efficiencies in the order of 2 × 10⁻³ (for SiO₂:Er) or 2 × 10⁻⁴(all other matrices) for lower current densities. The EL is excited by the impact of hot electrons with an excitation cross section in the range of 0.5–1.5 × 10⁻¹⁵cm⁻². Whereas the fraction of potentially excitable Er ions in SiO₂ can reach values up to 50%, five times lower values were observed for other matrices. The decrease of the EL decay time for devices with Si-rich SiO₂ or Si nitride compared to SiO₂ as host matrix implies an increase of the number of defects adding additional non-radiative de-excitation paths for Er³⁺. For all investigated devices, EL quenching cross sections in the 10⁻²⁰ cm² range and charge-to-breakdown values in the range of 1–10 C cm⁻² were measured. For the present design with a SiO₂ acceleration layer, thickness reduction and the use of different host matrices did not improve the EL power efficiency or the operation lifetime, but strongly lowered the operation voltage needed to achieve intense EL.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

A comprehensive study of the magnetic, structural, and transport properties of the III-V ferromagnetic semiconductor InMnP

The manganese induced magnetic, electrical, and structural modification in InMnP epilayers, prepared by Mn ion implantation and pulsed laser annealing, are investigated in the following work. All samples exhibit clear hysteresis loops and strong spin polarization at the Fermi level. The degree of magnetization, the Curie temperature, and the spin polarization depend on the Mn concentration. The bright-field transmission electron micrographs show that InP samples become almost amorphous after Mn implantation but recrystallize after pulsed laser annealing. We did not observe an insulator-metal transition in InMnP up to a Mn concentration of 5 at. %. Instead all InMnP samples show insulating characteristics up to the lowest measured temperature. Magnetoresistance results obtained at low temperatures support the hopping conduction mechanism in InMnP. We find that the Mn impurity band remains detached from the valence band in InMnP up to 5 at. % Mn doping. Our findings indicate that the local environment of Mn ions in InP is similar to GaMnAs, GaMnP, and InMnAs; however, the electrical properties of these Mn implanted III-V compounds are different. This is one of the consequences of the different Mn binding energy in these compounds.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Mechanism of β-FeSi{sub 2} precipitates growth-and-dissolution and pyramidal defects' formation during oxidation of Fe-contaminated silicon wafers

Fe-implanted Si-wafers have been oxidized at 900 °C and 1100 °C in order to investigate the behaviour of Fe atoms at the growing SiO{sub 2}/Si interface and the impact on the integrity of microelectronic devices of an involuntary Fe contamination before or during the oxidation process. As-implanted and oxidized wafers have been characterized using secondary ion mass spectroscopy, atom probe tomography, and high-resolution transmission electron microscopy. Experimental results were compared to calculated implantation profiles and simulated images. Successive steps of iron disilicide precipitation and oxidation were evidenced during the silicon oxidation process. The formation of characteristic pyramidal-shaped defects, at the SiO{sub 2}/Si interface, was notably found to correlate with the presence of β-FeSi{sub 2} precipitates. Taking into account the competitive oxidation of these precipitates and of the surrounding silicon matrix, dynamic mechanisms are proposed to model the observed microstructural evolution of the SiO{sub 2}/Si interface, during the growth of the silicon oxide layer.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Integration of quantum cascade lasers and passive waveguides

We report on monolithic integration of active quantum cascade laser (QCL) materials with passive waveguides formed by using proton implantation. Proton implantation reduces the electron concentration in the QCL layers by creating deep levels that trap carriers. This strongly reduces the intersubband absorption and the free-carrier absorption in the gain region and surrounding layers, thus significantly reducing optical loss. We have measured loss as low as α = 0.33 cm{sup −1} in λ = 9.6 μm wavelength proton-implanted QCL material. We have also demonstrated lasing in active-passive integrated waveguides. This simple integration technique is anticipated to enable low-cost fabrication in infrared photonic integrated circuits in the mid-infrared (λ ∼ 3–16 μm)

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Polyhydroxybutyrate/valerate/polycaprolactone small-diameter vascular graft: Experimental study of integration into organism

We prepared polyhydroxybutyrate/valerate (PHBV)/polylcaprolactone (PCL) small-diameter vascular grafts using electrospinning. Surface structure was assessed by scanning electron microscopy whilst physicomechanical properties were investigated by longitudinal uniaxial tension testing. Patency of grafts implanted into the rat abdominal aorta was evaluated using a Doppler ultrasonography at 2 week, 1 month and 12 month postimplantation. In addition, we assessed local histological features, along with IL-1β, IL-2, IL-4, IL-10, TNFa, TGF-β1, and VEGF serum levels. We revealed that only 2 (25%) grafts were not thrombosed at 2 week and 1 month postimplantation. However, at 12 month postimplantation a satisfactory histological pattern was observed in 50% of all cases, and we detected a monolayer of endothelial cells on the inner graft surface in half the cases. Regarding other grafts, we revealed minor connective tissue hyperplasia in 41.7% of the grafts and an inflammatory infiltrate in the part of the arterial wall in 8.3% of the grafts. We found that the IL-1β serum level was 3.5-fold higher in the group of experimental rats at 12 month postimplantation (p < 0.01). In addition, the IL-2 and IL-4 serum levels at 12 month postimplantation were 2- and 2.8-fold higher as compared to short-term implantation (2 weeks and 1 month) and control rats (p < 0.05) whilst the IL-10 serum level at 1 and 12 month postimplantation was more than 100-fold higher in comparison with 2 week postimplantation and control rats (p < 0.001). Serum VEGF was detected only at 12 month postimplantation. All in all, we created a biocompatible PHBV/PCL small-diameter vascular graft with a high surface area to volume ratio. A long-term patency of biodegradable vascular grafts after implantation into the rat abdominal aorta and the absence of a considerable immune response confirmed a high biocompatibility of such construct and the possibility of its use as a vascular graft.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Impurity and defect interactions during laser thermal annealing in Ge

The microscopic mechanisms involving dopants, contaminants, and defects in Ge during pulsed melting laser thermal annealing (LTA) are investigated in detail. Samples both un-implanted and implanted with As or B are processed by LTA as well as characterized in terms of chemical (1D and 3D), electrical, and strain profiling. The clustering of As is directly measured by 3D chemical profiling and correlated with its partial electrical activation along with a reduction of the lattice strain induced by As atoms. A semi-quantitative microscopic model involving the interaction with mobile As-vacancy (AsV) complexes is proposed to describe the clustering mechanism. Boron is shown to follow different clustering behavior that changes with depth and marked by completely different strain levels. Oxygen penetrates from the surface into all the samples as a result of LTA and, only in un-implanted Ge, it occupies an interstitial position inducing also positive strain in the lattice. On the contrary, data suggest that the presence of As or B forces O to assume different configurations with negligible strain, through O-V or O-B interactions for the two dopant species, respectively. These data suggest that LTA does not inject a significant amount of vacancies in Ge, at variance with Si, unless As atoms or possibly other n-type dopants are present. These results have to be carefully considered for modeling the LTA process in Ge and its implementation in technology.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Incorporation of dopant impurities into a silicon oxynitride matrix containing silicon nanocrystals

Dopant impurities, such as gallium (Ga), indium (In), and phosphorus (P), were incorporated into silicon-rich silicon oxynitride (SRSON) thin films by the ion implantation technique. To form silicon nanoparticles, the implanted layers were thermally annealed at temperatures up to 1100 °C for 60 min. This thermal treatment generates a phase separation of the silicon nanoparticles from the SRSON matrix in the presence of the dopant atoms. We report on the position of the dopant species within the host matrix and relative to the silicon nanoparticles, as well as on the effect of the dopants on the crystalline structure and the size of the Si nanoparticles. The energy-filtered transmission electron microscopy technique is thoroughly used to identify the chemical species. The distribution of the dopant elements within the SRSON compound is determined using Rutherford backscattering spectroscopy. Energy dispersive X-ray mapping coupled with spectral imaging of silicon plasmons was performed to spatially localize at the nanoscale the dopant impurities and the silicon nanoparticles in the SRSON films. Three different behaviors were observed according to the implanted dopant type (Ga, In, or P). The In-doped SRSON layers clearly showed separated nanoparticles based on indium, InOx, or silicon. In contrast, in the P-doped SRSON layers, Si and P are completely miscible. A high concentration of P atoms was found within the Si nanoparticles. Lastly, in Ga-doped SRSON the Ga atoms formed large nanoparticles close to the SRSON surface, while the Si nanoparticles were localized in the bulk of the SRSON layer. In this work, we shed light on the mechanisms responsible for these three different behaviors.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Effects of antimony (Sb) on electron trapping near SiO{sub 2}/4H-SiC interfaces

To investigate the mechanism by which Sb at the SiO{sub 2}/SiC interface improves the channel mobility of 4H-SiC MOSFETs, 1 MHz capacitance measurements and constant capacitance deep level transient spectroscopy (CCDLTS) measurements were performed on Sb-implanted 4H-SiC MOS capacitors. The measurements reveal a significant concentration of Sb donors near the SiO{sub 2}/SiC interface. Two Sb donor related CCDLTS peaks corresponding to shallow energy levels in SiC were observed close to the SiO{sub 2}/SiC interface. Furthermore, CCDLTS measurements show that the same type of near-interface traps found in conventional dry oxide or NO-annealed capacitors are present in the Sb implanted samples. These are O1 traps, suggested to be carbon dimers substituted for O dimers in SiO{sub 2}, and O2 traps, suggested to be interstitial Si in SiO{sub 2}. However, electron trapping is reduced by a factor of ∼2 in Sb-implanted samples compared with samples with no Sb, primarily at energy levels within 0.2 eV of the SiC conduction band edge. This trap passivation effect is relatively small compared with the Sb-induced counter-doping effect on the MOSFET channel surface, which results in improved channel transport.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗