In this study, we provide the first experimental evidence that colloidal hydrophilic magnetite nanoparticles can penetrate through bilayer lipid membrane in a non-uniform stationary magnetic field. Hydrophilic ligand-free cationic colloidal magnetite nanoparticles with an average diameter of 4 nm were added to the surrounding aqueous solution on one side of the azolectin membrane. An external non-uniform magnetic field ensured the attraction of superparamagnetic magnetite nanoparticles to the membrane, resulting in the formation of a near-membrane charged layer of cationic nanoparticles resulting in the initial polarization of the membrane. As a result of the passage of magnetite nanoparticles through the membrane, the polarization of the membrane decreases, and the membrane becomes depolarized. Independent methods were used to detect magnetite nanoparticles that passed through the lipid membrane including transmission electron microscopy and energy-dispersive x-ray spectroscopy. The discovered effect may be due to the following factors and interactions of nanoparticles. Interaction of magnetic nanoparticles with external inhomogeneous magnetic field provides localization of nanoparticles on the membrane surface. Collective interactions between nanoparticles, as well as their interactions with external electric and magnetic fields, lead to the formation of magnetite nanoparticle aggregates. Interaction of nanoparticles with the membrane lipid matrix leads to the formation of organic-inorganic complexes in which the polar surface of nanoparticles is enveloped by a lipid layer. The penetration of nanoparticles through the membrane is caused by the interaction of organic-inorganic complexes of nanoparticles and their aggregates with local intramembrane and near-membrane electric and magnetic fields.

An array consisting of three sensors was used for correlation measurements of thermal acoustic radiation. For the first time, all cross-correlation functions were obtained for each pair of sensors. The measurements were carried out at two positions of the source (a heated narrow Teflon cylinder), the distance between which was equal to half the spatial period of the cross-correlation function of adjacent sensors. The measured correlation functions were in antiphase, which corresponds to the calculated correlation functions of thermal acoustic radiation. To pass from correlation functions to temperature distribution, spatial cross-correlation functions for adjacent and the outermost sensors in the array are summed. The correlation methodology makes it possible to significantly increase the spatial resolution of the method.

In medicine, the monitoring of local hyperthermia requires painless measurements of the deep temperature with an error not exceeding 0.5–1 К and spacial resolution no worse than 5 mm. For temperature measurements, the use of passive acoustic thermometry is proposed based on the registration of the inherent thermal acoustic noise of the object. The measurements of the noise signal require a considerable integration time: in the megahertz range, attaining a desired accuracy requires that the signal be averaged during 30–50 s. To reduce this time without loss of accuracy, we propose to restore the temperature using the heat equation with blood flow. Local deep hyperthermia of the human soft tissues was examined. The three-dimensional heat equation (governing the deep temperature) was integrated with respect to depth, with a weight coefficient accounting for the absorption of ultrasound, subject to the instrument function of the receiving detector, to obtain a differential equation for the acoustobrightness temperature (measured signal). It was shown that, during the initial stage of the heating (~ 5 min), the distribution of the acoustobrightness temperature on the body surface satisfies approximately the 2D heat equation whose parameters are uniquely determined by the 3D heat equation governing the distribution of the deep temperature. Computations were carried out using the values of the thermal conductivity coefficient, specific blood flow, and ultrasound absorption coefficient typical for the soft tissues of the human organism as well as typical parameters of the source in the local, five-minute heating of soft tissues. The acoustobrightness temperature was computed in the standard way, using the known integral expression, with and without the detector instrument function, as well as through the solution of the obtained 2D heat equation. The discrepancy between the acoustobrightness temperatures computed through the different procedures grows with time but after five minutes of heating, it does not exceed the measurement error. A condition was introduced to determine the acceptability of the approximation made. The proposed approximation enables determination of the heat equation parameters from acoustobrightness temperature measurements, which makes it possible to compute the deep temperature distribution at any point in time.

The effect of pluronics L61 and F68 containing hydrophobic poly(propylene oxide) blocks of the same length and hydrophilic poly(ethylene oxide) blocks of different lengths on the conductance of planar bilayer lipid membranes made of azolectine is investigated. The conductance of these membranes increases as the concentration of both pluronics increases. For the same concentration of pluronics in solution, the conductance is higher for L61. Based on the literature data, the concentration of pluronics bound with the bilayer is calculated. For the close concentration of membrane-bound pluronics, the conductance of membranes is also close. It is concluded that in the first approximation, the appearance of the same hydrophobic parts of pluronics L61 and F68 in a membrane is accompanied by the same increase in its conductance. The conductance vs. concentration curves are superlinear for L61 and sublinear for F68. In the presence of either of these pluronics, the conduction spikes with the amplitude from 10 to 300 pSm and higher are observed for approximately 40

The front and back surface temperature of the hand was investigated with method of the medical thermography in the article. We used the infrared thermometer (UNI-T, China) and portable computer thermograph IRTIS-2000 (IRTIS, Moscow, Russia). The study was conducted on a group of subjects, consisting of 50 people, 17 men and 33 women, aged 18 to 23 years. The average temperature difference between the palm and the back of the hand was 0.21 ± 0.16 °С. It was also found that not all subjects had a palm temperature higher than the temperature of the back of the hand. A ten-day study was conducted separately on one patient to determine how the temperature difference of the left and right hands changed in the morning, afternoon and evening. He initially had a temperature on the back of his hand higher than his palm. Analysis of the data for the entire sample confirmed the assumption that the surface temperature of the palm is higher than the temperature of the back (р < 0.05). However, when the groups of men and women were examined separately, the difference was negligible (р > 0.05). The discussion part includes articles that studies hand temperature in obesity and vibration disease.

In the magnetofection method, magnetic fields and magnetic nanoparticles are used to increase the efficiency of gene delivery into cells. Magnefection enhances the introduction into cells of gene vectors with which magnetic nanoparticles are associated, due to the action of a magnetic field that holds the nanoparticles in the area of their application. It is believed that the magnetic field itself does not change the mechanism of absorption (endocytosis) of nanoparticles. Both the beneficial effect of magnetofection - delivery of the vector into the cell, and its side effect - cytotoxicity are associated with the interaction of particles with cell membranes and, in particular, with lipid bilayers. In our work, we investigated the effect of an applied stationary inhomogeneous magnetic field and spherical superparamagnetic magnetite nanoparticles with a diameter of about 4 nm on the conductivity of azolectin bilayer lipid membranes. The membranes were formed in a stationary magnetic field with a magnetic induction of up to 26 mT. The magnetic field had no effect on the conductivity of the membrane. After monitoring the membrane conductivity, magnetic nanoparticles were added to the solution surrounding the membrane. The addition was carried out on one side of the membrane so that the magnetic field attracted nanoparticles to the membrane surface. After adding nanoparticles in a magnetic field, the conductivity of the membranes increased by one to two orders of magnitude. This effect was observed for all membranes. A smooth increase in conductivity was accompanied in a number of cases (for 25% of the membranes) by the appearance of current jumps, which can be associated with the formation of through conducting pores with a radius of about 0.5 nm. The conductivity increased with increasing magnetic field gradient.

The integral conductance of planar lipid bilayer membranes in the presence of two Poloxamers (Pluronics) L61 and F68 with the same lengths of hydrophobic poly(propylene oxide) blocks and the different lengths of hydrophilic poly(ethylene oxide) blocks increases with an increase in the concentration of both Pluronics; however, the shape of the conductance-concentration curves is super linear for L61 and sublinear for F68. In the presence of both Pluronics, rare discrete current jumps are observed against the background of continuous current. At high concentrations, the I–V curves of membranes with both L61 and F68 became nonlinear at sufficiently low voltages but differed significantly. At voltages greater than 50 mV, the conductance of membranes with L61 increased sharply and quantized jumps were observed toward higher conductance, which could be interpreted as the appearance of additional pores. On the contrary, the conductance of membranes with F68 decreased and quantized jumps to lower conductance were observed, which could be interpreted as blocking of already existing pores. We attributed the differences in the conductance-concentration and I–V curves of these two Pluronics to their different effects on the dynamics of membrane hydration and, accordingly, on the probability of formation of conducting pores.

The study of the electrical parameters of asolectin bilayer lipid membranes in the presence of cytochrome c (cyt c) at various concentrations showed that an increase in the concentration of cyt c leads to an increase in the membrane conductance and the appearance of through pores. The studied membranes did not contain cardiolipin, which is commonly used in studying the effect of cyt c on membrane permeability. In the presence of cyt c, discrete current fluctuations were recorded. The occurrence of these fluctuations may be associated with the formation of through pores. The diameter of these pores was ~0.8 nm, which is smaller than the size of the cyt c globule (~3 nm). Measurements carried out at pH values from 6.4 to 8.4 showed that the concentration dependence of the membrane conductance increases with increasing pH. To assess the binding of cyt c to the bilayer, we measured the concentration and pH dependences of the difference in surface potentials induced by the unilateral addition of cyt c. The amount of bound cyt c at the same concentrations decreased with increasing pH, which did not correspond to the conductance trend. An analysis of conductance traces leads to the conclusion that an increase in the integral conductance of membranes is associated with an increase in the lifetime of pores. The formation of "long-lived" pores, of which the residence time in the open state is longer than in the closed state, was achieved at various combinations of pHs and cyt c concentrations: the higher the pH, the lower the concentration at which the long-lived pores appeared and, accordingly, a higher conductance was observed. The increase in conductance and the formation of transmembrane pores are not due to the electrostatic interaction between cyt c and the membrane. We hypothesize that an increase in pH leads to a weakening of hydrogen bonds between lipid heads, which allows cyt c molecules to penetrate into the membrane. This disrupts the order of the bilayer and leads to the occurrence of through pores.

Targeted drug delivery is one of the most important areas in pharmacology. The drug can be placed in a liposomal shell and destroyed it in a specific location in the body using electroporation. In many experiments on the study of electroporation, the bilayer lipid membrane BLM (black film) is used as a model for the action of an electric field. The characteristic pore size during electroporation is several nanometers, which corresponds to the membrane thickness. These pores can be visualized using cryoelectron microscopy or atomic force microscopy. However, we cannot observe with the help of these methods the dynamics of pores: changes in their number in the membrane and changes in their size over time. We suggest using 100-500 nm color film until it has turned into a black BLM film as the BLM model. Metastable pore-defects about 6 µm in size were registered in the color film, which were observed with a light microscope (video is attached, pore-defects appear at the very end of the recording). The temporal characteristics of the registered pore-defects were considered: the lifetime of pores before membrane rupture, the rate of increase in the number of pores in the membrane. The results obtained show that a thick colored film can be used as a BLM model for studying the process of pore formation during electroporation.

Inelastic (dissipative) effects of different natures in lipid bilayer membranes can lead to hysteresis phenomena. Early, it was shown that lipid bilayer membranes, under the action of a periodic sinusoidal voltage, demonstrate pinched-hysteresis loops in the experimental capacitance–voltage dependences and are almost the only example of the physical implementation of memcapacitance. Here, we propose an equivalent circuit and mathematical framework for analyzing the dynamic nonlinear current response of a lipid bilayer membrane as an externally controlled memcapacitance. Solving a nonlinear differential equation for the equivalent circuit of a membrane in the form of a parallel connection of a nonlinear viscoelastic capacitor and an active resistance using the small parameter method, we obtain explicit analytical dependences for the current response of the membrane and pinched-hysteresis loops. The explicit solutions and their comparison with experimental data allow us to identify the lumped equivalent circuit parameters that govern the memcapacitor behavior of the membrane and hence the magnitude of the hysteresis. We quantify the memcapacitance hysteresis in terms of negative work done by the control signal. An analysis of the formulas leads to the conclusion that the determining factor for the appearance of pinched hysteresis is the type of nonlinear dependence of the device capacitance on voltage.

Structural changes in phosphatidylcholine lipid membranes caused by the introduction of insoluble CoFe2O4 nanoparticles (NPs) are analyzed. Changes in nuclear magnetic resonance spectrum, infrared spectrum, and ionic conductivity of membranes are observed with the addition of NPs. The presence of NPs in membranes is proved by atomic force and magnetic force microscopy. Structural changes in the membranes in the vicinity of the lipid C-O bonds caused by NPs are observed by Scanning near-field optical microscopy. Analysis of nuclear magnetic resonance (NMR) spectra allowed us to identify the affected atomic groups in the membrane surface layers. Conductivity measurements of the bilayer membranes were performed in DC as well as in time-resolved modes. Hydrophobic NPs stimulate surface distortion and creation of pores, which depending on NP concentration leads to an increase in the ionic conductivity of membranes. Concentration dependence demonstrating percolation threshold was analyzed in the frame of the fractal theory approach.

In this work we performed UHF heating with an electromagnetic field of frequency 40.68 MHz and power of 30 W on human forearms and phantoms made of plastisol with simulated blood flow at physiotherapeutic doses of 10, 15 and 20 minutes. Thermal acoustic radiation of heated objects measured with a multichannel acoustothermograph with a bandwidth of 1.6-2.5 MHz, an integration time of 10 C, and a threshold sensitivity of 0.2 K. Additionally, the surface temperature of the forearm measured by infrared thermometry and the internal temperature of the phantom by an electronic thermometer. We obtained data about temperature distribution patterns in the human forearm and in the plastisol phantom. Blood flow in the phantoms was simulated by copper, aluminum and polyvinyl chloride tubes, through which water from a thermostat was passed. Comparison of cooling rates of different types of phantoms showed that the thermal properties of the phantom with aluminum tubes were the closest to the soft tissues of the human forearm. The data of objective control do not agree with the subjective sensations of the subjects, but agree well with each other, which confirms the necessity and shows the possibility of objective assessment of temperature distribution parameters in the soft tissues of the human body during hyperthermia during UHF-physiotherapy.

Passive acoustic thermometry (PAT) was used to study the dynamics of changes in the chest temperature of a person with COVID-19 over the course of about two and a half weeks after quarantine. PAT, which can measure deep body temperature, showed that the integral temperature of tissues surrounding the lungs increased from 32.2 ± 0.07 to 33.0 ± 0.03°C about 10 days after the end of quarantine. This may indicate increased blood supply to the lungs, i.e., an indication of recovery. Infrared thermometry used to monitor recovery yielded no results.

We measured the conductance of bilayer lipid membranes of diphytanoylphosphatidylcholine induced by interaction with cubic magnetic nanoparticles (MNPs) of cobalt ferrite 12 and 27 nm in size and coated with a hydrophilic shell. The MNP coating is human serum albumin (HSA) or polyethylene glycol (PEG). The interaction of nanoparticles added to the bulk solution with the lipid bilayer causes the formation of metastable conductive pores, which, in turn, increases the integral conductance of the membranes. The increase in conductance with increasing MNP concentration was practically independent of the particle size. The dependence of the bilayer conductance on the concentration of PEG-coated MNPs was much weaker than that on the concentration with a shell of HSA. Analyzing the current traces, we believe that the conductive pores formed as a result of the interaction of nanoparticles with the membrane can change their size, remaining metastable. The form of multilevel current traces allows us to assume that there are several metastable pore states close in energy. The average radius of the putative cylindrical pores is in the range of 0.4–1.3 nm.

An algorithm for reconstructing the time-varying one-dimensional distribution of the deep temperature of the human body under local heating is proposed and experimentally tested on a model. The algorithm requires that the temperature obey the heat conduction equation, the integration of which with a weight that takes into account absorption in the object, makes it possible to obtain the time dependence of the acoustic brightness temperature (measured signal), which in turn is determined by the parameters of the equation. The desired temperature is obtained by solving the heat conduction equation with the found parameters. The algorithm reconstructs two parameters: blood flow and the amplitude of the heating source, which are not determined each time anew, but only refined. In this case, the integration time increases, but the temporal resolution does not suffer: new results can be obtained after any period of time. After 2 min of heating, it is possible to reconstruct the temperature and size of the heated region with an accuracy acceptable for medical applications: 0.5°C and 0.5 mm, respectively.

Magnetic nanoparticles are widely used in medical applications, for example, as contrast agents for magnetic resonance imaging, to enhance hyperthermia, for targeted drug delivery, theranostics (therapy + diagnostics). When used in vivo, magnetic nanoparticles require a special coating that promotes biocompatibility and minimizes potential toxicity under physiological conditions. Human serum albumin or polyethylene glycol can be used as a coating. In this work, the interactions of magnetic cobalt ferrite nanoparticles (12 and 27 nm size) with diphitanoylphosphatidylcholine bilayer lipid membranes were investigated. The conductivity of membranes varied over a wide range – two groups of membranes can be distinguished – membranes, the conductivity of which (after the addition of nanoparticles) remained practically unchanged compared to the control, and membranes, the conductivity of which, upon the addition of nanoparticles, changed abruptly and increased in a wide range by 0.5–2 orders of magnitude. Significant differences between the conductivities upon the addition of the same volume of 12 and 27 nm nanoparticles surrounded by human serum albumin were not found. When adding nanoparticles with a coating of polyethylene glycol, the conductivity increased much weaker than when adding nanoparticles with a coating of human serum albumin. The results suggest that hydrophilic coated magnetic nanoparticles interact with the membranes, which can lead to the appearance of metastable conducting pores, which, in turn, increase the integral conductivity of the membranes.

The electrical conductivity of azolectine bilayer lipid membranes is observed to increase 10–40-fold with respect to its background value of 67 ± 13 pS/mm2 upon the addition of cubic CoFe2O4 nanoparticles with the main diagonal of 14 nm (MNP-14) and 27 nm (MNP-27). As the concentration of MNP-14 in the membrane solution increases from 50 to 450 µg/mL, the increase in the membrane conductivity with respect to its background value is nonlinear and can be approximated by the exponential dependence with exponent 2.75. Discrete current pulses are observed in the constant voltage mode for the MNP-14 concentration higher than 250 µg/mL and for all MNP-27 concentrations starting from 50 µg/mL, which points to the appearance of conducting lipid pores.

We describe the dynamics of lipoic acid (LA) alone, incorporated in liposomes and as a part of nanoemulsions. Mass spectrometry shows that LA in water forms aggregates of two or three molecules in the form of a negatively charged ion and a neutral molecule. Phosphatidylcholine (PC)-based nanoforms of LA as liposomes and nanoemulsions with a particle size equal to 145 nm are characterized by a high degree of incorporation of LA into the nanoparticles and long-term stability during storage at room temperature. Dynamic light scattering (DLS) gives the polydispersity index of the nanoforms (> 0.3), characterizing the homogeneity of the obtained nanodispersions. We found that such emulsions can significantly (5 ×) increase the concentration of LA in the aqueous phase (5–7 mg/mL) when compared with an aqueous solution of LA (1 mg/mL) and by 40% when compared with PC liposomes (4 mg/mL). Moreover, the inclusion of LA in liposomes and nanoemulsions from PC did not change the neutral ζ-potential characteristic of PC nanoforms. CryoTEM established that the structural organization of the liposomes practically did not differ from nanoemulsions and both nanoforms contained both multilayer and single-layer vesicles. When studying the release kinetics of LA from phosphatidylcholine nanoforms, we found that at 22 h, 45–55% of LA was released from nanoparticles, but that at the initial stage of the process LA was slowly released from the nanoemulsions and rapidly from the liposomes. Conductance measurements indicate that LA delivered in all the three forms increase membrane permeability, though this result is most marked with the LA in PC liposomes.

We report on the estimation of blood content and vessel volume fraction changes in the microcirculatory bed of human skin under controlled mechanical compression using 3-dimensional optoacoustic (OA) angiography. A consecutive decrease in the fraction of blood vessels and skin blood content as a result of an increase in pressure from 0 to 72 mmHg applied to the imaged area was demonstrated by means of an acoustical-resolution OA microscope with a spatial resolution of 50 mu m. Pressures below 32 mmHg were shown to weakly affect the acquired OA angiograms. The loss of OA signal from the blood vessels was observed after a further pressure increase of up to 72 mmHg. The vascular changes observed by OA microscopy were confirmed by infrared (IR) thermometry measurements which revealed similar dynamics of microcirculation interruption in the area under pressure.