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1.
J Pineal Res ; 76(5): e12986, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38965880

RESUMO

This contribution reviews the role of inbred and transgenic mouse strains for deciphering the mammalian melatoninergic and circadian system. It focusses on the pineal organ as melatonin factory and two major targets of the melatoninergic system, the suprachiasmatic nuclei (SCN) and the hypophysial pars tuberalis (PT). Mammalian pinealocytes sharing molecular characteristics with true pineal and retinal photoreceptors synthesize and secrete melatonin into the blood and cerebrospinal fluid night by night. Notably, neuron-like connections exist between the deep pinealocytes and the habenular/pretectal region suggesting direct pineal-brain communication. Control of melatonin biosynthesis in rodents involves transcriptional regulation including phosphorylation of CREB and upregulation of mPer1. In the SCN, melatonin acts upon MT1 and MT2 receptors. Melatonin is not necessary to maintain the rhythm of the SCN molecular clockwork, but it has distinct effects on the synchronization of the circadian rhythm by light, facilitates re-entrainment of the circadian system to phase advances in the level of the SCN molecular clockwork by acting upon MT2 receptors and plays a stabilizing role in the circadian system as evidenced from locomotor activity recordings. While the effects in the SCN are subtle, melatonin is essential for PT functions. Via the MT1 receptor it drives the PT-intrinsic molecular clockwork and the retrograde and anterograde output pathways controlling seasonal rhythmicity. Although inbred and transgenic mice do not show seasonal reproduction, the pathways from the PT are fully intact if the animals are melatonin proficient. Thus, only melatonin-proficient strains are suited to investigate the circadian and melatoninergic systems.


Assuntos
Ritmo Circadiano , Melatonina , Animais , Melatonina/metabolismo , Ritmo Circadiano/fisiologia , Camundongos , Modelos Animais , Núcleo Supraquiasmático/metabolismo , Camundongos Transgênicos , Glândula Pineal/metabolismo
2.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 41(3): 455-460, 2024 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-38932530

RESUMO

The main magnetic field, generated by the excitation coil of the magnetic induction phase shift technology detection system, is mostly dispersed field with small field strength, and the offset effect needs to be further improved, which makes the detection signal weak and the detection system difficult to achieve quantitative detection, thus the technology is rarely used in vivo experiments and clinical trials. In order to improve problems mentioned above, a new Helmholtz birdcage sensor was designed. Stimulation experiment was carried out to analyze the main magnetic field in aspects of intensity and magnetic distribution, then different bleeding volume and bleeding rates experiments were conducted to compared with traditional sensors. The results showed that magnetic field intensity in detection region was 2.5 times than that of traditional sensors, cancellation effect of the main magnetic field was achieved, the mean value of phase difference of 10 mL rabbit blood was (-3.34 ± 0.21)°, and exponential fitting adjusted R 2 between phase difference and bleeding volumes and bleeding rates were both 0.99. The proposed Helmholtz birdcage sensor has a uniform magnetic field with a higher field strength, enable more accurate quantification of hemorrhage and monitored change of bleeding rates, providing significance in magnetic induced technology research for cerebral hemorrhage detection.


Assuntos
Hemorragia Cerebral , Campos Magnéticos , Animais , Coelhos
3.
Ecology ; 105(7): e4334, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38887829

RESUMO

Ecological theory predicts that kelp forests structured by trophic cascades should experience recovery and persistence of their foundation species when herbivores become rare. Yet, climate change may be altering the outcomes of top-down forcing in kelp forests, especially those located in regions that have rapidly warmed in recent decades, such as the Gulf of Maine. Here, using data collected annually from 30+ sites spanning >350 km of coastline, we explored the dynamics of Maine's kelp forests in the ~20 years after a fishery-induced elimination of sea urchin herbivores. Although forests (Saccharina latissima and Laminaria digitata) had broadly returned to Maine in the late 20th century, we found that forests in northeast Maine have since experienced slow but significant declines in kelp, and forest persistence in the northeast was juxtaposed by a rapid, widespread collapse in the southwest. Forests collapsed in the southwest apparently because ocean warming has-directly and indirectly-made this area inhospitable to kelp. Indeed, when modeling drivers of change using causal techniques from econometrics, we discovered that unusually high summer seawater temperatures the year prior, unusually high spring seawater temperatures, and high sea urchin densities each negatively impacted kelp abundance. Furthermore, the relative power and absolute impact of these drivers varied geographically. Our findings reveal that ocean warming is redefining the outcomes of top-down forcing in this system, whereby herbivore removal no longer predictably leads to a sustained dominance of foundational kelps but instead has led to a waning dominance (northeast) or the rise of a novel phase state defined by "turf" algae (southwest). Such findings indicate that limiting climate change and managing for low herbivore abundances will be essential for preventing further loss of the vast forests that still exist in northeast Maine. They also more broadly highlight that climate change is "rewriting the rules" of nature, and thus that ecological theory and practice must be revised to account for shifting species and processes.


Assuntos
Pesqueiros , Cadeia Alimentar , Kelp , Animais , Kelp/fisiologia , Mudança Climática , Maine , Oceanos e Mares , Ouriços-do-Mar/fisiologia , New England , Fatores de Tempo , Herbivoria
4.
ACS Nano ; 18(27): 17622-17629, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38922204

RESUMO

Engineering atomic-scale defects has become an important strategy for the future application of transition metal dichalcogenide (TMD) materials in next-generation electronic technologies. Thus, providing an atomic understanding of the electron-defect interactions and supporting defect engineering development to improve carrier transport is crucial to future TMDs technologies. In this work, we utilize low-temperature scanning tunneling microscopy/spectroscopy (LT-STM/S) to elicit how distinct types of defects bring forth scattering potential engineering based on intervalley quantum quasiparticle interference (QPI) in TMDs. Furthermore, quantifying the energy-dependent phase variation of the QPI standing wave reveals the detailed electron-defect interaction between the substitution-induced scattering potential and the carrier transport mechanism. By exploring the intrinsic electronic behavior of atomic-level defects to further understand how defects affect carrier transport in low-dimensional semiconductors, we offer potential technological applications that may contribute to the future expansion of TMDs.

5.
Sensors (Basel) ; 24(11)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38894435

RESUMO

This article proposes a distributed intelligent Coordinated Multi-Point Non-Orthogonal Multiple-Access (CoMP-NOMA) collaborative transmission model with the assistance of reconfigurable intelligent surfaces (RISs) to address the issues of poor communication quality, low fairness, and high system power consumption for edge users in multi-cellular networks. By analyzing the interaction mechanisms and influencing factors among RIS signal enhancement, NOMA user scheduling, and multi-point collaborative transmission, the model establishes RIS-enhanced edge user grouping and coordinates NOMA user clusters based on this. In the multi-cell RIS-assisted JT-CoMP NOMA downlink transmission, joint optimization of the power allocation (PA), user clustering (UC), and RIS phase-shift matrix design (PS) poses a challenging Mixed-Integer Non-Linear Programming (MINLP) problem. The original problem is decomposed by optimizing the formulas into joint sub-problems of PA, UC, and PA and PS, and solved using an alternating optimization approach. Simulation results demonstrate that the proposed scheme effectively reduces the system's power consumption while significantly improving the system's throughput and rates.

6.
Sensors (Basel) ; 24(12)2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38931660

RESUMO

Thanks to the recent development of innovative instruments and software with high accuracy and resolution, 3D modelling provides useful insights in several sectors (from industrial metrology to cultural heritage). Moreover, the 3D reconstruction of objects of artistic interest is becoming mandatory, not only because of the risks to which works of art are increasingly exposed (e.g., wars and climatic disasters) but also because of the leading role that the virtual fruition of art is taking. In this work, we compared the performance of four 3D instruments based on different working principles and techniques (laser micro-profilometry, structured-light topography and the phase-shifting method) by measuring four samples of different sizes, dimensions and surface characteristics. We aimed to assess the capabilities and limitations of these instruments to verify their accuracy and the technical specifications given in the suppliers' data sheets. To this end, we calculated the point densities and extracted several profiles from the models to evaluate both their lateral (XY) and axial (Z) resolution. A comparison between the nominal resolution values and those calculated on samples representative of cultural artefacts was used to predict the performance of the instruments in real case studies. Overall, the purpose of this comparison is to provide a quantitative assessment of the performance of the instruments that allows for their correct application to works of art according to their specific characteristics.

7.
Sensors (Basel) ; 24(9)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38732879

RESUMO

Grating (moiré) interferometry is one of the well-known methods for full-field in-plane displacement and strain measurement. There are many design solutions for grating interferometers, including systems with a microinterferometric waveguide head. This article proposes a modification to the conventional waveguide interferometer head, enabling the implementation of a polarization fringe phase shift for automatic fringe pattern analysis. This article presents both the theoretical considerations associated with the proposed solution and its experimental verification, along with the concept of in-plane displacement/strain sensing using the described head.

8.
J Pineal Res ; 76(4): e12961, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38751172

RESUMO

Melatonin is a neurohormone synthesized from dietary tryptophan in various organs, including the pineal gland and the retina. In the pineal gland, melatonin is produced at night under the control of the master clock located in the suprachiasmatic nuclei of the hypothalamus. Under physiological conditions, the pineal gland seems to constitute the unique source of circulating melatonin. Melatonin is involved in cellular metabolism in different ways. First, the circadian rhythm of melatonin helps the maintenance of proper internal timing, the disruption of which has deleterious effects on metabolic health. Second, melatonin modulates lipid metabolism, notably through diminished lipogenesis, and it has an antidiabetic effect, at least in several animal models. Third, pharmacological doses of melatonin have antioxidative, free radical-scavenging, and anti-inflammatory properties in various in vitro cellular models. As a result, melatonin can be considered both a circadian time-giver and a homeostatic monitor of cellular metabolism, via multiple mechanisms of action that are not all fully characterized. Aging, circadian disruption, and artificial light at night are conditions combining increased metabolic risks with diminished circulating levels of melatonin. Accordingly, melatonin supplementation could be of potential therapeutic value in the treatment or prevention of metabolic disorders. More clinical trials in controlled conditions are needed, notably taking greater account of circadian rhythmicity.


Assuntos
Ritmo Circadiano , Homeostase , Melatonina , Melatonina/metabolismo , Animais , Humanos , Ritmo Circadiano/fisiologia , Homeostase/fisiologia , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/fisiologia , Glândula Pineal/metabolismo
9.
Front Neurosci ; 18: 1186677, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694901

RESUMO

DNA aptamers can bind specifically to biomolecules to modify their function, potentially making them ideal oligonucleotide therapeutics. Herein, we screened for DNA aptamer of melanopsin (OPN4), a blue-light photopigment in the retina, which plays a key role using light signals to reset the phase of circadian rhythms in the central clock. Firstly, 15 DNA aptamers of melanopsin (Melapts) were identified following eight rounds of Cell-SELEX using cells expressing melanopsin on the cell membrane. Subsequent functional analysis of each Melapt was performed in a fibroblast cell line stably expressing both Period2:ELuc and melanopsin by determining the degree to which they reset the phase of mammalian circadian rhythms in response to blue-light stimulation. Period2 rhythmic expression over a 24-h period was monitored in Period2:ELuc stable cell line fibroblasts expressing melanopsin. At subjective dawn, four Melapts were observed to advance phase by >1.5 h, while seven Melapts delayed phase by >2 h. Some Melapts caused a phase shift of approximately 2 h, even in the absence of photostimulation, presumably because Melapts can only partially affect input signaling for phase shift. Additionally, some Melaps were able to induce phase shifts in Per1::luc transgenic (Tg) mice, suggesting that these DNA aptamers may have the capacity to affect melanopsin in vivo. In summary, Melapts can successfully regulate the input signal and shifting phase (both phase advance and phase delay) of mammalian circadian rhythms in vitro and in vivo.

10.
Mar Pollut Bull ; 203: 116462, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38749153

RESUMO

Analyzing the environmental factors affecting benthic communities in coastal areas is crucial for uncovering key factors that require conservation action. Here, we collected benthic and environmental (physical-chemical-historical and land-based) data for 433 transects in Taiwan. Using a k-means approach, five communities dominated by crustose coralline algae, turfs, stony corals, digitate, or bushy octocorals were first delineated. Conditional random forest models then identified physical, chemical, and land-based factors (e.g., light intensity, nitrite, and population density) relevant to community delineation and occurrence. Historical factors, including typhoons and temperature anomalies, had only little effect. The prevalent turf community correlated positively with chemical and land-based drivers, which suggests that anthropogenic impacts are causing a benthic homogenization. This mechanism may mask the effects of climate disturbances and regional differentiation of benthic assemblages. Consequently, management of nutrient enrichment and terrestrial runoff is urgently needed to improve community resilience in Taiwan amidst increasing challenges of climate change.


Assuntos
Antozoários , Mudança Climática , Monitoramento Ambiental , Taiwan , Animais , Ecossistema , Biodiversidade
11.
Netw Neurosci ; 8(1): 293-318, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38562290

RESUMO

Recently, in the past decade, high-frequency oscillations (HFOs), very high-frequency oscillations (VHFOs), and ultra-fast oscillations (UFOs) were reported in epileptic patients with drug-resistant epilepsy. However, to this day, the physiological origin of these events has yet to be understood. Our study establishes a mathematical framework based on bifurcation theory for investigating the occurrence of VHFOs and UFOs in depth EEG signals of patients with focal epilepsy, focusing on the potential role of reduced connection strength between neurons in an epileptic focus. We demonstrate that synchronization of a weakly coupled network can generate very and ultra high-frequency signals detectable by nearby microelectrodes. In particular, we show that a bistability region enables the persistence of phase-shift synchronized clusters of neurons. This phenomenon is observed for different hippocampal neuron models, including Morris-Lecar, Destexhe-Paré, and an interneuron model. The mechanism seems to be robust for small coupling, and it also persists with random noise affecting the external current. Our findings suggest that weakened neuronal connections could contribute to the production of oscillations with frequencies above 1000 Hz, which could advance our understanding of epilepsy pathology and potentially improve treatment strategies. However, further exploration of various coupling types and complex network models is needed.


We have built a mathematical framework to examine how a reduced neuronal coupling within an epileptic focus could lead to very high-frequency (VHFOs) and ultra-fast oscillations (UFOs) in depth EEG signals. By analyzing weakly coupled neurons, we found a bistability synchronization region where in-phase and anti-phase synchrony persist. These dynamics can be detected as very high-frequency EEG signals. The principle of weak coupling aligns with the disturbances in neuronal connections often observed in epilepsy; moreover, VHFOs are important markers of epileptogenicity. Our findings point to the potential significance of weakened neuronal connections in producing VHFOs and UFOs related to focal epilepsy. This could enhance our understanding of brain disorders. We emphasize the need for further investigations of weakly coupled neurons.

12.
Nano Lett ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38604944

RESUMO

The phase-shift, transmittance, and polarization properties of meta-atoms are investigated, motivated by their use as building blocks of metasurfaces used in metalenses, holograms, and beam shaping. We studied dielectric nanorod meta-atoms of several geometries, which included cylinders, triangles, squares, hexagons, octagons, and truncated cones. By analyzing light propagation through these meta-atoms for three different wavelengths (632.8, 545, and 50 nm), we show that the phase-shift introduced is independent of their cross-section shape, contrary to the expected behavior. Additionally, we show that the polarization response is independent of the shape and that the transmittance is partially shape-independent. We identify a novel dependence of phase-shift on the effective cross-sectional area of meta-atoms. These meta-atom optical properties are independent of its shape if its geometry has a C3 or larger rotational symmetry. This optical invariance has significant implications for the topological optimization of flat optics.

13.
Nanomaterials (Basel) ; 14(8)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38668203

RESUMO

An integrated optical isolator is a crucial part of photonic integrated circuits (PICs). Existing optical isolators, predominantly based on the silicon-on-insulator (SOI) platform, face challenges in integrating with active devices. We propose a broadband, compact TM mode Mach-Zehnder optical isolator based on InP-on-insulator platforms. We designed two distinct magneto-optical waveguide structures, employing different methods for bonding Ce:YIG and InP, namely O2 plasma surface activation direct wafer bonding and DVS-benzocyclobutene (BCB) adhesive bonding. Detailed calculations and optimizations were conducted to enhance their non-reciprocal phase shift (NRPS). At a wavelength of 1550 nm, the direct-bonded waveguide structure achieved a 30 dB bandwidth of 72 nm with a length difference of 0.256 µm. The effects of waveguide arm length, fabrication accuracy, and dimensional errors on the device performance are discussed. Additionally, manufacturing tolerances for three types of lithographic processes were calculated, serving as references for practical manufacturing purposes.

14.
Sensors (Basel) ; 24(5)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38475149

RESUMO

Advanced sensing technologies and communication capabilities of Connected and Autonomous Vehicles (CAVs) empower them to capture the dynamics of surrounding vehicles, including speeds and positions of those behind, enabling judicious responsive maneuvers. The acquired dynamics information of vehicles spurred the development of various cooperative platoon controls, particularly designed to enhance platoon stability with reduced spacing for reliable roadway capacity increase. These controls leverage abundant information transmitted through various communication topologies. Despite these advancements, the impact of different vehicle dynamics information on platoon safety remains underexplored, as current research predominantly focuses on stability analysis. This knowledge gap highlights the critical need for further investigation into how diverse vehicle dynamics information influences platoon safety. To address this gap, this research introduces a novel framework based on the concept of phase shift, aiming to scrutinize the tradeoffs between the safety and stability of CAV platoons formed upon bidirectional information flow topology. Our investigation focuses on platoon controls built upon bidirectional information flow topologies using diverse dynamics information of vehicles. Our research findings emphasize that the integration of various types of information into CAV platoon controls does not universally yield benefits. Specifically, incorporating spacing information can enhance both platoon safety and string stability. In contrast, velocity difference information can improve either safety or string stability, but not both simultaneously. These findings offer valuable insights into the formulation of CAV platoon control principles built upon diverse communication topologies. This research contributes a nuanced understanding of the intricate interplay between safety and stability in CAV platoons, emphasizing the importance of information dynamics in shaping effective control strategies.

15.
Nanomaterials (Basel) ; 14(5)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38470731

RESUMO

Integrated optical isolators are important building blocks for photonic integrated chips. Despite significant advances in isolators integrated on silicon-on-insulator (SOI) platforms, integrated isolators on GaAs-on-insulator platforms are rarely reported. In this paper, two structural designs of optical isolators based on the TM basic mode of GaAs-on-insulator are proposed. The non-reciprocal phase shift (NRPS) of GaAs/Ce:YIG waveguides with different geometric structures are calculated using numerical simulation. The isolators achieve 35 dB isolation bandwidths greater than 53.5 nm and 70 nm at 1550 nm, with total insertion losses of 2.59 dB and 2.25 dB, respectively. A multi-mode interferometric (MMI) coupler suitable for these two structures is proposed. In addition, suitable manufacturing processes are discussed based on the simulated process tolerances.

16.
Sci Rep ; 14(1): 6208, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38485981

RESUMO

Recent years have seen a rise in interest in wind energy as a useful alternative to harmful energies like fossil fuels. The dual rotor wind turbine (DRWT) offers more rapid rates of wind energy extraction. The current study intends to compare the performance of the turbine with and without the addition of a second rotor. Additionally, it examines how tip speed ratio and phase shift angle will affect DRWT performance. Realizable k-shear stress transport turbulence models are used to solve the three-dimensional, turbulent, stable, and incompressible flow equations for the performance of dual-rotor wind turbines. Domain-independence tests and an impartial mesh test are run to assess the results and ensure their accuracy. The researcher relies on previous studies while constructing the single rotor wind turbine model. This model uses an S826 airfoil. The front and rear rotors are given streamlined representations using ANSYS, according to the researcher. The independent mesh test indicates that the mesh density has 11.5 million elements. The experiment's results show that the DRWT has a significant effect on the efficiency of wind energy.

17.
Proc Natl Acad Sci U S A ; 121(7): e2315787121, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38315864

RESUMO

Charge transport in solids at low temperature reveals a material's mesoscopic properties and structure. Under a magnetic field, Shubnikov-de Haas (SdH) oscillations inform complex quantum transport phenomena that are not limited by the ground state characteristics and have facilitated extensive explorations of quantum and topological interest in two- and three-dimensional materials. Here, in elemental metal Cr with two incommensurately superposed lattices of ions and a spin-density-wave ground state, we reveal that the phases of several low-frequency SdH oscillations in [Formula: see text] and [Formula: see text] are no longer identical but opposite. These relationships contrast with the SdH oscillations from normal cyclotron orbits that maintain identical phases between [Formula: see text] and [Formula: see text] . We trace the origin of the low-frequency SdH oscillations to quantum interference effects arising from the incommensurate orbits of Cr's superposed reciprocal lattices and explain the observed [Formula: see text]-phase shift by the reconnection of anisotropic joint open and closed orbits.

18.
Biomimetics (Basel) ; 9(2)2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38392149

RESUMO

Stable communication technologies in complex waters are a prerequisite for underwater operations. Underwater acoustic communication is susceptible to multipath interference, while underwater optical communication is susceptible to environmental impact. The underwater electric field communication established based on the weak electric fish perception mechanism is not susceptible to environmental interference, and the communication is stable. It is a new type of underwater communication technology. To address issues like short communication distances and high bit error rates in existing underwater electric field communication systems, this study focuses on underwater electric field communication systems based on direct sequence spread spectrum (DSSS) and binary phase shift keying (BPSK) modulation techniques. To verify the feasibility of the established spread spectrum electric field communication system, static communication experiments were carried out in a swimming pool using the DSSS-based system. The experimental results show that in fresh water with a conductivity of 739 µS/cm, the system can achieve underwater current electric field communication within a 11.2 m range with 10-6 bit errors. This paper validates the feasibility of DSSS BPSK in short-range underwater communication, and compact communication devices are expected to be deployed on underwater robots for underwater operations.

19.
Ultrason Sonochem ; 103: 106754, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38252981

RESUMO

Phase-shift droplets are a highly adaptable platform for biomedical applications of ultrasound. The spatiotemporal response of phase-shift droplets to focused ultrasound above a certain pressure threshold, termed acoustic droplet vaporization (ADV), is influenced by intrinsic features (e.g., bulk boiling point) and extrinsic factors (e.g., driving frequency and surrounding media). A deep understanding of ADV dynamics is critical to ensure the robustness and repeatability of an ADV-assisted application. Here, we integrated ultra-high-speed imaging, at 10 million frames per second, and confocal microscopy for a full-scale (i.e., from nanoseconds to seconds) characterization of ADV. Experiments were conducted in fibrin-based hydrogels to mimic soft tissue environments. Effects of fibrin concentration (0.2 to 8 % (w/v)), excitation frequency (1, 2.5, and 9.4 MHz), and perfluorocarbon core (perfluoropentane, perfluorohexane, and perfluorooctane) on ADV dynamics were studied. Several fundamental parameters related to ADV dynamics, such as expansion ratio, expansion velocity, collapse radius, collapse time, radius of secondary rebound, resting radius, and equilibrium radius of the generated bubbles were extracted from the radius vs time curves. Diffusion-driven ADV-bubble growth was fit to a modified Epstein-Plesset equation, adding a material stress term, to estimate the growth rate. Our results indicated that ADV dynamics were significantly impacted by fibrin concentration, frequency, and perfluorocarbon liquid core. This is the first study to combine ultra-high-speed and confocal microscopy techniques to provide insights into ADV bubble dynamics in tissue-mimicking hydrogels.


Assuntos
Fluorocarbonos , Volatilização , Acústica , Hidrogéis , Fibrina
20.
Nanotheranostics ; 8(1): 33-47, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38164499

RESUMO

Rationale: Microvascular obstruction (MVO) following percutaneous coronary intervention (PCI) is a common problem associated with adverse clinical outcomes. We are developing a novel treatment, termed sonoreperfusion (SRP), to restore microvascular patency. This entails using ultrasound-targeted microbubble cavitation (UTMC) of intravenously administered gas-filled lipid microbubbles (MBs) to dissolve obstructive microthrombi in the microvasculature. In our prior work, we used standard-sized lipid MBs. In the present study, to improve upon the efficiency and efficacy of SRP, we sought to determine the therapeutic efficacy of fibrin-targeted phase shift microbubbles (FTPSMBs) in achieving successful reperfusion of MVO. We hypothesized that owing to their much smaller size and affinity for thrombus, FTPSMBs would provide more effective dissolution of microthrombi when compared to that of the corresponding standard-sized lipid MBs. Methods: MVO in the rat hindlimb was created by direct injection of microthrombi into the left femoral artery. Definity MBs (Lantheus Medical Imaging) were infused through the jugular vein for contrast-enhanced ultrasound imaging (CEUS). A transducer was positioned vertically above the hindlimb for therapeutic US delivery during the concomitant administration of various therapeutic formulations, including (1) un-targeted MBs; (2) un-targeted phase shift microbubbles (PSMBs); (3) fibrin-targeted MB (FTMBs); and (4) fibrin-targeted PSMBs (FTPSMBs). CEUS cine loops with burst replenishment were obtained at baseline (BL), 10 min post-MVO, and after each of two successive 10-minute SRP treatment sessions (TX1, TX2) and analyzed (MATLAB). Results: In-vitro binding affinity assay showed increased fibrin binding peptide (FBP) affinity for the fibrin clots compared with the untargeted peptide (DK12). Similarly, in our in-vitro model of MVO, we observed a higher binding affinity of fluorescently labeled FTPSMBs with the porcine microthrombi compared to FTMBs, PSMBs, and MBs. Finally, in our hindlimb model, we found that UTMC with FTPSMBs yielded the greatest recovery of blood volume (dB) and flow rate (dB/sec) following MVO, compared to all other treatment groups. Conclusions: SRP with FTPSMBs achieves more rapid and complete reperfusion of MVO compared to FTMBs, PSMBs, and MBs. Studies to explore the underlying physical and molecular mechanisms are underway.


Assuntos
Microbolhas , Intervenção Coronária Percutânea , Ratos , Animais , Suínos , Ultrassonografia , Peptídeos , Lipídeos
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