Reordering and synchronization of electrical turbulence in cardiac tissue through global and partial optogenetical illumination.

Electrical turbulence in the heart is considered the culprit of cardiac disease, including the fatal ventricular fibrillation. Optogenetics is an emerging technology that has the capability to produce action potentials of cardiomyocytes to affect the electric wave propagation in cardiac tissue, thereby possessing the potential to control the turbulence, by shining a rotating spiral pattern onto the tissue. In this paper, we present a method to reorder and synchronize electrical turbulence through optogenetics. A generic two-variable reaction-diffusion model and a simplified three-variable ionic cardiac model are used. We discuss cases involving either global or partial illumination.

Global trend and future landscape of intestinal microcirculation research from 2000 to 2021: A scientometric study.

BACKGROUND: The intestinal microcirculation functions in food absorption and metabolic substance exchanges. Accumulating evidence indicates that intestinal microcirculatory dysfunction is a significant source of multiple gastrointestinal diseases. To date, there has not been a scientometric analysis of intestinal microcirculatory research. AIM: To investigate the current status, development trends, and frontiers of intestinal microcirculatory research based on bibliometric analysis. METHODS: VOSviewer and CiteSpace 6.1.R2 were used to identify the overall characteristics and knowledge map of intestinal microcirculatory research based on the core literature published from 2000 to 2021 in the Web of Science database. The characteristics of each article, country of origin, institution, journal, cocitations, and other information were analyzed and visualized. RESULTS: There were 1364 publications enrolled in the bibliometric analysis, exhibiting an upward trend from 2000 to 2021 with increased participation worldwide. The United States and Dalhousie University took the lead among countries and institutions, respectively. Shock was the most prolific journal, and Nature Reviews Microbiology Clinical had the most citations. The topical hotspots and frontiers in intestinal microcirculatory research were centered on the pathological processes of functional impairment of intestinal microvessels, diverse intestinal illnesses, and clinical treatment. CONCLUSION: Our study highlights insights into trends of the published research on the intestinal microcirculation and offers serviceable guidance to researchers by summarizing the prolific areas in intestinal disease research to date.

Role of insulin in pancreatic microcirculatory oxygen profile and bioenergetics.

BACKGROUND: The pancreatic islet microcirculation adapts its metabolism to cope with limited oxygen availability and nutrient delivery. In diabetes, the balance between oxygen delivery and consumption is impaired. Insulin has been proven to exert complex actions promoting the maintenance of homeostasis of the pancreas under glucotoxicity. AIM: To test the hypothesis that insulin administration can improve the integrated pancreatic microcirculatory oxygen profile and bioenergetics. METHODS: The pancreatic microcirculatory partial oxygen pressure (PO2), relative hemoglobin (rHb) and hemoglobin oxygen saturation (SO2) were evaluated in nondiabetic, type 1 diabetes mellitus (T1DM), and insulin-treated mice. A three-dimensional framework was generated to visualize the microcirculatory oxygen profile. Ultrastructural changes in the microvasculature were examined using transmission electron microscopy. An Extracellular Flux Analyzer was used to detect the real-time changes in bioenergetics by measuring the oxygen consumption rate and extracellular acidification rate in islet microvascular endothelial cells (IMECs). RESULTS: Significantly lower PO2, rHb, and SO2 values were observed in T1DM mice than in nondiabetic controls. Insulin administration ameliorated the streptozotocin-induced decreases in these microcirculatory oxygen parameters and improved the mitochondrial ultrastructural abnormalities in IMECs. Bioenergetic profiling revealed that the IMECs did not have spare respiratory capacity. Insulin-treated IMECs exhibited significantly greater basal respiration than glucotoxicity-exposed IMECs (P < 0.05). An energy map revealed increased energetic metabolism in insulin-treated IMECs, with significantly increased ATP production, non-mitochondrial respiration, and oxidative metabolism (all P < 0.05). Significant negative correlations were revealed between microcirculatory SO2 and bioenergetic parameters. CONCLUSION: Glucotoxicity deteriorates the integrated pancreatic microcirculatory oxygen profile and bioenergetics, but this deterioration can be reversed by insulin administration.

The circulating level of miR-122 is a potential risk factor for endothelial dysfunction in young patients with essential hypertension.

MicroRNAs are key molecules involved in the regulation of endothelial function. They are important risk factors and biomarkers for the development of hypertension related to endothelial dysfunction. However, the gene expression patterns associated with hypertension development related to endothelial dysfunction have not been fully elucidated. We conducted a case-control study of 65 patients with essential hypertension (EH) and 61 controls without EH. Plasma levels of miR-122 and its target protein high-affinity cationic amino acid transporter 1 (CAT-1) were measured by qRT-PCR and ELISA, respectively. miR-122 expression in plasma of patients with EH was significantly higher than that of the control group (p = 0.001), while CAT-1 expression in patients with EH was significantly lower than that in the control group (p = 0.018). miR-122 expression in plasma of young patients with EH was significantly higher than that in young people without EH (p = 0.0004), and CAT-1 expression in plasma of young patients with EH was also significantly lower than that of the control group (p = 0.002). CAT-1 expression in the plasma of young participants was significantly higher than that of individuals aged ≥40 years (p = 0.003), whereas miR-122 expression was significantly lower (p = 0.001). We showed that among patients with EH, the high expression of miR-122 contributed to endothelial dysfunction by suppressing the expression of the CAT-1 protein, which led to a decrease in CAT-1 expression in plasma. Therefore, high expression of miR-122 appears to be a risk factor for endothelial dysfunction in EH, especially in younger patients.

Selection of spatiotemporal patterns in arrays of spatially distributed oscillators indirectly coupled via a diffusive environment.

Emergence of self-organized behaviors in diverse living systems often depends on population density. In these systems, cell-cell communications are usually mediated by the surrounding environment. Collective behaviors (e.g., synchrony and dynamical quorum sensing) of such systems with stirred environment have been extensively studied, but the spatiotemporal dynamics of the oscillators coupled via a diffusive environment (without stirring) is rather understudied. We here perform a computational study on the selection and competition of wave patterns in arrays of spatially distributed oscillators immersed in a diffusive medium. We find that population density plays a crucial role in the selection of wave patterns: (i) for a single spiral in the system, its rotation either inward or outward could be controlled by population density, and (ii) for spiral and target waves coexisting initially in the system, wave competition happens and population density decides which type of wave will finally survive. The latter phenomenon is further confirmed in a system whose individual element is excitable rather than self-sustained oscillatory. The mechanism underlying all these observations is attributed to the frequency competition. Our results in the excitable case may have implications on the experimental results.

Spiral wave chimeras in locally coupled oscillator systems.

The recently discovered chimera state involves the coexistence of synchronized and desynchronized states for a group of identical oscillators. In this work, we show the existence of (inwardly) rotating spiral wave chimeras in the three-component reaction-diffusion systems where each element is locally coupled by diffusion. A transition from spiral waves with the smooth core to spiral wave chimeras is found as we change the local dynamics of the system or as we gradually increase the diffusion coefficient of the activator. Our findings on the spiral wave chimera in the reaction-diffusion systems suggest that spiral chimera states may be found in chemical and biological systems that can be modeled by a large population of oscillators indirectly coupled via a diffusive environment.

Phase-locked scroll waves defy turbulence induced by negative filament tension.

Scroll waves in a three-dimensional media may develop into turbulence due to negative tension of the filament. Such negative tension-induced instability of scroll waves has been observed in the Belousov-Zhabotinsky reaction systems. Here we propose a method to restabilize scroll wave turbulence caused by negative tension in three-dimensional chemical excitable media using a circularly polarized (rotating) external field. The stabilization mechanism is analyzed in terms of phase-locking caused by the external field, which makes the effective filament tension positive. The phase-locked scroll waves that have positive tension and higher frequency defy the turbulence and finally restore order. A linear theory for the change of filament tension caused by a generic rotating external field is presented and its predictions closely agree with numerical simulations.

Gelatinases promote calcification of vascular smooth muscle cells by up-regulating bone morphogenetic protein-2.

Matrix metalloproteinase-2 (MMP-2), also known as gelatinase A, is involved in vascular calcification. Another member of gelatinases is MMP-9 (gelatinase B). However, the role of gelatinases in the pathogenesis of vascular calcification is not well understood. The current study aims to clarify the relationship between gelatinases and vascular calcification and to elucidate the underlying mechanism. Beta-glycerophosphate (ß-GP) was used to induce calcification of vascular smooth muscle cells (VSMCs) with or without 2-[[(4-Phenoxyphenyl)sulfonyl]methyl]-thiirane (SB-3CT), a specific gelatinases inhibitor. Levels of calcification were determined by assessing calcium content and calcification area of VSMCs. Phenotype transition of VSMCs was observed by assessing expressions of alkaline phosphatase (ALP), smooth muscle α-actin (SM-α-actin) and desmin. Gelatin zymography was applied to determine the activities of gelatinases, and western blot was applied to determine expressions of gelatinases, bone morphogenetic protein-2 (BMP-2), Runt-related transcription factor 2 (RUNX2) and msh homeobox homolog 2 (Msx-2). Gelatinases inhibition by SB-3CT alleviated calcification and phenotype transition of VSMCs induced by ß-GP. Increased gelatinases expression and active MMP-2 were observed in calcifying VSMCs. Gelatinases inhibition reduced expression of RUNX2, Msx-2 and BMP-2. BMP-2 treatment increased expressions of RUNX2 and Msx-2, while noggin, an antagonist of BMP-2, decreased expressions of RUNX2 and Msx-2. Gelatinases promote vascular calcification by upregulating BMP-2 which induces expression of RUNX2 and Msx-2, two proteins associated with phenotype transition of VSMCs in vascular calcification. Interventions targeting gelatinases inhibition might be a proper candidate for ameliorating vascular calcification.

Biomechanical tactics of chiral growth in emergent aquatic macrophytes.

Through natural selection, many plant organs have evolved optimal morphologies at different length scales. However, the biomechanical strategies for different plant species to optimize their organ structures remain unclear. Here, we investigate several species of aquatic macrophytes living in the same natural environment but adopting distinctly different twisting chiral morphologies. To reveal the principle of chiral growth in these plants, we performed systematic observations and measurements of morphologies, multiscale structures, and mechanical properties of their slender emergent stalks or leaves. Theoretical modeling of pre-twisted beams in bending and buckling indicates that the different growth tactics of the plants can be strongly correlated with their biomechanical functions. It is shown that the twisting chirality of aquatic macrophytes can significantly improve their survivability against failure under both internal and external loads. The theoretical predictions for different chiral configurations are in excellent agreement with experimental measurements.

Chiral selection and frequency response of spiral waves in reaction-diffusion systems under a chiral electric field.

Chirality is one of the most fundamental properties of many physical, chemical, and biological systems. However, the mechanisms underlying the onset and control of chiral symmetry are largely understudied. We investigate possibility of chirality control in a chemical excitable system (the Belousov-Zhabotinsky reaction) by application of a chiral (rotating) electric field using the Oregonator model. We find that unlike previous findings, we can achieve the chirality control not only in the field rotation direction, but also opposite to it, depending on the field rotation frequency. To unravel the mechanism, we further develop a comprehensive theory of frequency synchronization based on the response function approach. We find that this problem can be described by the Adler equation and show phase-locking phenomena, known as the Arnold tongue. Our theoretical predictions are in good quantitative agreement with the numerical simulations and provide a solid basis for chirality control in excitable media.

Unpinning of rotating spiral waves in cardiac tissues by circularly polarized electric fields.

Spiral waves anchored to obstacles in cardiac tissues may cause lethal arrhythmia. To unpin these anchored spirals, comparing to high-voltage side-effect traditional therapies, wave emission from heterogeneities (WEH) induced by the uniform electric field (UEF) has provided a low-voltage alternative. Here we provide a new approach using WEH induced by the circularly polarized electric field (CPEF), which has higher success rate and larger application scope than UEF, even with a lower voltage. And we also study the distribution of the membrane potential near an obstacle induced by CPEF to analyze its mechanism of unpinning. We hope this promising approach may provide a better alternative to terminate arrhythmia.

Reversal of spiral waves in an oscillatory system caused by an inhomogeneity.

Spatial heterogeneities are commonly found in realistic systems and play significant roles in dynamics of spiral waves. We here demonstrate a novel phenomenon that a localized inhomogeneity put around the spiral core could lead to the reversal of spiral waves in an oscillatory system, e.g., the complex Ginzburg-Landau equation. With the amplitude-phase representation, we analyze underling mechanism and conditions of the wave reversal in detail, which is found to agree with the numerical evidence.

Chiralities of spiral waves and their transitions.

The chiralities of spiral waves usually refer to their rotation directions (the turning orientations of the spiral temporal movements as time elapses) and their curl directions (the winding orientations of the spiral spatial geometrical structures themselves). Traditionally, they are the same as each other. Namely, they are both clockwise or both counterclockwise. Moreover, the chiralities are determined by the topological charges of spiral waves, and thus they are conserved quantities. After the inwardly propagating spirals were experimentally observed, the relationship between the chiralities and the one between the chiralities and the topological charges are no longer preserved. The chiralities thus become more complex than ever before. As a result, there is now a desire to further study them. In this paper, the chiralities and their transition properties for all kinds of spiral waves are systemically studied in the framework of the complex Ginzburg-Landau equation, and the general relationships both between the chiralities and between the chiralities and the topological charges are obtained. The investigation of some other models, such as the FitzHugh-Nagumo model, the nonuniform Oregonator model, the modified standard model, etc., is also discussed for comparison.

Chiral symmetry breaking in a reaction-diffusion system.

The emergence of order in far-from-equilibrium systems is often accompanied by the formation of spatially asymmetric patterns. About 30 years ago, a general mechanism to select a chiral solution by coupling a reaction-diffusion system to an external chiral electric field was proposed by Nicolis and Prigogine [Proc. Natl. Acad. Sci. USA 78, 659 (1981)]. However, no experimental or even numerical evidence in reaction-diffusion systems has been reported yet. Here we report a chiral symmetry-breaking phenomenon in a reaction-diffusion system coupled to a circularly polarized electric field (CPEF). Specifically, we show that the CPEF breaks the zero-rotation chiral symmetry between clockwise and counterclockwise spiral defects and that ordered spiral waves with preferred chirality arise from defect-mediated turbulence. The occurrence of such chiral symmetry breaking can be understood by the competition between spiral defects with opposite chirality.

Synchronization and quorum sensing in an ensemble of indirectly coupled chaotic oscillators.

The fact that the elements in some realistic systems are influenced by each other indirectly through a common environment has stimulated a new surge of studies on the collective behavior of coupled oscillators. Most of the previous studies, however, consider only the case of coupled periodic oscillators, and it remains unknown whether and to what extent the findings can be applied to the case of coupled chaotic oscillators. Here, using the population density and coupling strength as the tuning parameters, we explore the synchronization and quorum sensing behaviors in an ensemble of chaotic oscillators coupled through a common medium, in which some interesting phenomena are observed, including the appearance of the phase synchronization in the process of progressive synchronization, the various periodic oscillations close to the quorum sensing transition, and the crossover of the critical population density at the transition. These phenomena, which have not been reported for indirectly coupled periodic oscillators, reveal a corner of the rich dynamics inherent in indirectly coupled chaotic oscillators, and are believed to have important implications to the performance and functionality of some realistic systems.

Inwardly rotating spirals in nonuniform excitable media.

Inwardly rotating spirals (IRSs) have attracted great attention since their observation in an oscillatory reaction-diffusion system. However, IRSs have not yet been reported in planar excitable media. In the present work we investigate rotating waves in a nonuniform excitable medium, consisting of an inner disk part surrounded by an outer ring part with different excitabilities, by numerical simulations of a simple FitzHugh-Nagumo model. Depending on the excitability of the medium as well as the inhomogeneity, we find the occurrence of IRSs, of which the excitation propagates inwardly to the geometrical spiral tip.

Coherent wave patterns sustained by a localized inhomogeneity in an excitable medium.

The influence of a localized inhomogeneity (oscillatory or stationary) on spatiotemporal chaotic state in an excitable reaction-diffusion system is investigated. We find that various coherent wave patterns, such as spiral waves (including multiarmed) and target wave patterns are able to be created by the inhomogeneity from the chaotic state. Due to the growth of these coherent wave patterns, the previously existing turbulent waves in the absence of inhomogeneity are suppressed. At last, the whole system is entrained by the coherent wave patterns. Closer investigations indicate that the possible mechanisms underlying the inhomogeneity sustained coherent wave patterns seem quite different for oscillatory and stationary inhomogeneities.

Sinklike spiral waves in oscillatory media with a disk-shaped inhomogeneity.

Spiral wave propagation in oscillatory media with a disk-shaped inhomogeneity is examined. Depending on the properties of the medium as well as the inhomogeneity (different frequencies in two regions), distinct spiral waves including sinklike spirals and dense-sparse spirals, are able to emerge. We find that, unlike the previously found outward group velocity for spiral waves (normal spirals or antispirals), the direction of the velocity of the sinklike spiral wave points inward. A qualitative analysis of the possible mechanism underlying their formation is discussed, considering the inhomogeneity as a wave sink or source. Numerical simulations performed on other typical reaction-diffusion models confirm this analysis and suggest that our findings are robust and could be observed in experiments.

Transition from Turing stripe patterns to hexagonal patterns induced by polarized electric fields.

The effect of a circularly polarized electric field on the Turing stripe patterns is studied. The numerical results show that stripe patterns may change to hexagonal wave patterns by choosing the intensity and the frequency of the circularly polarized electric field suitably. Our findings indicate that a pattern tends to organize itself to the pattern with the same symmetry of the applied field with the fact that compared to the stripe patterns, hexagonal wave patterns possess hexagonal symmetry which is closer to the rotation symmetry of the circularly polarized electric field.