Author Correction:Mutual interaction of red blood cells influenced by nanoparticles (Scientific Reports, (2019), 9, 1, (5147), 10.1038/s41598-019-41643-x)

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Mutual interaction of red blood cells influenced by nanoparticles

Despite extensive studies on different types of nanoparticles as potential drug carriers, the application of red blood cells (RBCs) as natural transport agents for systemic drug delivery is considered a new paradigm in modern medicine and possesses great potential. There is a lack of studies on the influence of drug carriers of different compositions on RBCs, especially regarding their potential impact on human health. Here, we apply conventional microscopy to observe the formation of RBC aggregates and optical tweezers to quantitatively assess the mutual interaction of RBCs incubated with inorganic and polymeric nanoparticles. Scanning electron microscopy is utilized for direct observation of nanoparticle localization on RBC membranes. The experiments are performed in a platelet-free blood plasma mimicking the RBC natural environment. We show that nanodiamonds influence mutual RBC interactions more antagonistically than other nanoparticles, resulting in higher aggregation forces and the formation of larger cell aggregates. In contrast, polymeric particles do not cause anomalous RBC aggregation. The results emphasize the application of optical tweezers for the direct quantitative assessment of the mutual interaction of RBCs influenced by nanomaterials

Optical Tweezers in Studies of Red Blood Cells

Optical tweezers (OTs) are innovative instruments utilized for the manipulation of microscopic biological objects of interest. Rapid improvements in precision and degree of freedom of multichannel and multifunctional OTs have ushered in a new era of studies in basic physical and chemical properties of living tissues and unknown biomechanics in biological processes. Nowadays, OTs are used extensively for studying living cells and have initiated far-reaching influence in various fundamental studies in life sciences. There is also a high potential for using OTs in haemorheology, investigations of blood microcirculation and the mutual interplay of blood cells. In fact, in spite of their great promise in the application of OTs-based approaches for the study of blood, cell formation and maturation in erythropoiesis have not been fully explored. In this review, the background of OTs, their state-of-the-art applications in exploring single-cell level characteristics and bio-rheological properties of mature red blood cells (RBCs) as well as the OTs-assisted studies on erythropoiesis are summarized and presented. The advance developments and future perspectives of the OTs’ application in haemorheology both for fundamental and practical in-depth studies of RBCs formation, functional diagnostics and therapeutic needs are highlighted

Influence of Pulsed He–Ne Laser Irradiation on the Red Blood Cell Interaction Studied by Optical Tweezers

Optical Tweezers (OT), as a revolutionary innovation in laser physics, has been extremely useful in studying cell interaction dynamics at a single-cell level. The reversible aggregation process of red blood cells (RBCs) has an important influence on blood rheological properties, but the underlying mechanism has not been fully understood. The regulating effects of low-level laser irradiation on blood rheological properties have been reported. However, the influence of pulsed laser irradiation, and the origin of laser irradiation effects on the interaction between RBCs remain unclear. In this study, RBC interaction was assessed in detail with OT. The effects of both continuous and pulsed low-level He–Ne laser irradiation on RBC aggregation was investigated within a short irradiation period (up to 300 s). The results indicate stronger intercellular interaction between RBCs in the enforced disaggregation process, and both the cell contact time and the initial contact area between two RBCs showed an impact on the measured disaggregation force. Meanwhile, the RBC aggregation force that was independent to measurement conditions decreased after a short time of pulsed He–Ne laser irradiation. These results provide new insights into the understanding of the RBC interaction mechanism and laser irradiation effects on blood properties

Impact of Nanocapsules on Red Blood Cells Interplay Jointly Assessed by Optical Tweezers and Microscopy

In the framework of novel medical paradigm the red blood cells (RBCs) have a great potential to be used as drug delivery carriers. This approach requires an ultimate understanding of the peculiarities of mutual interaction of RBC influenced by nano-materials composed the drugs. Optical tweezers (OT) is widely used to explore mechanisms of cells’ interaction with the ability to trap non-invasively, manipulate and displace living cells with a notably high accuracy. In the current study, the mutual interaction of RBC with polymeric nano-capsules (NCs) is investigated utilizing a two-channel OT system. The obtained results suggest that, in the presence of NCs, the RBC aggregation in plasma satisfies the ‘cross-bridges’ model. Complementarily, the allocation of NCs on the RBC membrane was observed by scanning electron microscopy (SEM), while for assessment of NCs-induced morphological changes the tests with the human mesenchymal stem cells (hMSC) was performed. The combined application of OT and advanced microscopy approaches brings new insights into the conception of direct observation of cells interaction influenced by NCs for the estimation of possible cytotoxic effects

In vitro influence of 520 nm diode laser irradiation on red blood cell spontaneous aggregation studied by optical tweezers and light microscopy

The laser has biomodulation effects on blood properties thus could regulate the microcirculation. The laser-RBC interaction mechanism is unclear, whereas most studies provide statistical results and lack detailed observations of laser irradiation effects on blood rheology. This study is designated to probe the in vitro effects of 520 nm diode laser irradiation on red blood cells (RBCs) mutual interaction properties in spontaneous aggregation process in autologous plasma by optical tweezers (OTs), with an attempt to reveal the laser-RBC interaction outcomes at a single-cell level. The results preliminarily show that though the laser irradiation statistically inhibited the increase of the size of RBC aggregates compared with the non-irradiating group, the aggregation force between single RBCs increased slightly with the time of irradiation

Dihydrotachysterol: a bad choice in the treatment of chronic hypoparathyroidism

Hypoparathyroidism is an endocrine disease caused by damage of the parathyroid glands and characterized by underproduction of parathyroid hormone. This can lead to severe hypocalcemia and its associated complications. The chronic hypoparathyroidism requires lifelong therapy including calcium and vitamin D analogues. The goal of treatment is to maintain the target parameters of phosphorus-calcium metabolism. At the same time, there is a risk of iatrogenic hypercalcemia on the standard therapy, up to the hypercalcemic crisis, often complicated by the acute renal failure. Moreover, chronic hypercalcemia acts as a predisposing factor for nephrolithiasis, nephrocalcinosis, chronic renal failure including pre- and dialysis stages.Dihydrotachysterol is a synthetic analogue of vitamin D, which was previously widely prescribed for hypocalcaemic hypoparathyroidism. In accordance with modern Russian and international guidelines, this drug should not be used in the treatment of chronic hypoparathyroidism. The main features in the metabolism of dihydrotachysterol (long elimination period, lack of feedback regulation of the active metabolites, high biological activity) and a narrow therapeutic window cause the frequent development of hypercalcemia and associated disorders.We present several clinical cases of patients with hypoparathyroidism treated with dihydrotachysterol, which was complicated by severe hypercalcemia and acute renal failure

Hemorheological alterations of red blood cells induced by 450-nm and 520-nm laser radiation

Proper rheological properties of red blood cells (RBC) including flexibility and aggregability are essential for healthy blood microcirculation. Excessive RBC aggregation has been observed to be associated with many pathological conditions and is crucial in acute circulatory problems. Low-level laser radiation (LLLR) has been found to have positive effects on the rheology of human blood, however, the detailed mechanisms of blood photobiomodulation remains unclear. In this study, utilizing the single-cell technique optical tweezers (OT) and traditional light microscopy, the influence of photobiomodulation of human RBC was examined under different conditions of laser irradiation. The results revealed that high radiant exposure (over 170.5 J/cm 2 radiant fluence) caused enhanced RBC aggregation and cell shape transformation while the aggregation force between single RBC remained unchanged. LLLR with radiant fluence below 9.5 J/cm 2 by 450 nm wavelength improved the RBC deformability, weakened the strength of cell-cell interaction in the RBC disaggregation process, and showed rejuvenating effects on RBC suspended in a harsh cell environment

Формирование траектории беспилотного летательного аппарата при облете запретных зон

Considered the problem of flying over restricted areas by an unmanned aerial vehicle (UAV), which have various shapes and restrictions, set on the basis of the international airspace classification system for aviation in accordance with the Chicago Convention and the recommended principles for the formation of forbidden zones, rules for creating a flight route along forbidden zones and actions in case of border violations of restricted areas. The problem of analytical synthesis of the control acceleration of an unmanned aerial vehicle (UAV) is solved during its flight along a route passing along the boundaries of the forbidden zone of a given shape, along a given trajectory, which consists of subsequent segments located at the same height relative to the earth’s surface, in a given coordinate system. The optimal control synthesis problem is solved as an analytical definition of the optimal control of a linear non-stationary system based on the quadratic quality functional. A mathematical model of UAV motion in the horizontal plane is proposed, in the form of a system of ordinary differential equations in the Cauchy form. A law for measuring the control acceleration of the UAV’s center of mass is obtained on the basis of specifying the minimized quality functional and the corresponding constraints, which is a feature of the considered method of solving the problem. The proposed quality functional takes into account the parameters of coordinates and speed of the UAV, which correspond to the given points in the airspace, which characterize the necessary trajectory for flying around the restricted area. The derived mathematical dependences make it possible to implement them on board a UAV and minimize energy costs when guiding a UAV moving through specified points in space. Computer modeling of the derived analytical results, mathematical dependencies representing the optimal trajectory of the UAV flight along the boundaries of the forbidden zone, as well as the corresponding processes of changing the control acceleration and speed of the UAV movement was carried out, which made it possible to draw conclusions about the efficiency of the proposed method and the feasibility of its further use as a basis. for the initial stage of the synthesis of the UAV control system.Рассматривается задача облета запретных зон беспилотным летательным аппаратом (БЛА), имеющих различную форму и ограничения, задаваемых на основе международной система классификации воздушного пространства для авиации согласно Чикагской конвенции и рекомендуемых принципов формирования запретных зон, правил создания маршрута пролета вдоль запретных зон и действий при нарушении границ запретных зон. Решается задача аналитического синтеза управляющего ускорения беспилотного летательного аппарата (БЛА) при пролете его по маршруту, проходящему вдоль границ запретной зоны заданной формы, по заданной траектории, которая состоит из последовательных отрезков, находящихся на одинаковой высоте относительно земной поверхности, в заданной системе координат. Задача синтеза оптимального управления решается как аналитическое определение оптимального управления линейной нестационарной системой на основе квадратического функционала качества. Предложена математическая модель движения БЛА в горизонтальной плоскости, в виде системы обыкновенных дифференциальных уравнений в форме Коши. Получен закон изменения управляющего ускорения центра масс БЛА на основе задания минимизируемого функционала качества и соответствующих ограничений, что является особенностью рассмотренной методики решения задачи. Предложенный функционал качества учитывает параметры координат и скорости БЛА, которые соответствуют заданным точкам в воздушном пространстве, характеризующим необходимую траекторию для облета запретной зоны. Полученные математические зависимости дают возможность реализовать их на борту БЛА и минимизируют энергетические затраты при управлении БЛА, движущемся через заданные точки пространства. Было проведено компьютерное моделирование полученных аналитических результатов, математических зависимостей, представляющих собой оптимальную траекторию пролета БЛА вдоль границ запретной зоны, а также соответствующих процессов изменения управляющего ускорения и скорости движения БЛА, что позволило сделать выводы о работоспособности предложенной методики и целесообразность ее дальнейшего использования в качестве основы для первоначального этапа синтеза системы управления БЛА