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Modern radiotherapy utilizes a broad range of sources of ionizing radiation, both low-dose-rate (LDR) and high-dose-rate (HDR). However, the mechanisms underlying specific dose-rate effects remain unclear, especially for corpuscular radiation. To address this issue, we have irradiated human epidermoid carcinoma A431 cells under LDR and HDR regimes. Reducing the dose rate has lower lethality at equal doses with HDR irradiation. The half-lethal dose after HDR irradiation was three times less than after LDR irradiation. The study of mechanisms showed that under HDR irradiation, the radiation-induced halt of mitosis with the accompanying emergence of giant cells was recorded. No such changes were recorded after LDR irradiation. The level of DNA damage is significantly greater after HDR irradiation, which may be the main reason for the different mechanisms of action of HDR and LDR irradiations. Comparing the mechanisms of cell response to LDR and HDR irradiations may shed light on the mechanisms of tumor cell response to ionizing radiation and answer the question of whether different dose rates within the same dose range can cause different clinical effects.

Salinity impacts important processes in plants, reducing their yield. The effect of salinity on the cytosolic pH (pHcyt) has been little studied. In this research, we employed transgenic tobacco plants expressing the pH sensor Pt-GFP to investigate the alterations in pHcyt in cells across various root zones. Furthermore, we examined a wide spectrum of NaCl concentrations (ranging from 0 to 150 mM) and assessed morphological parameters and plant development. Our findings revealed a pattern of cytosolic acidification in cells across all root zones at lower NaCl concentrations (50, 100 mM). Interestingly, at 150 mM NaCl, pHcyt levels either increased or returned to normal, indicating a nonlinear effect of salinity on pHcyt. Most studied parameters related to development and morphology exhibited an inhibitory influence in response to NaCl. Notably, a nonlinear relationship was observed in the cell length within the elongation and differentiation zones. While cell elongation occurred at 50 and 100 mM NaCl, it was not evident at 150 mM NaCl. This suggests a complex interplay between stimulating and inhibitory effects of salinity, contributing to the nonlinear relationship observed between pHcyt, cell length, and NaCl concentration.

Electrical signals (ESs) appearing in plants under the action of various external factors play an important role in adaptation to changing environmental conditions. Generation of ES in higher plant cells is associated with activation of Ca2+, K+, and anion fluxes, as well as with changes in the activity of plasma membrane H+-ATPase. In the present review, molecular nature of the ion channels contributing to ESs transmission in higher plants is analyzed based on comparison of the data from molecular-genetic and electrophysiological studies. Based on such characteristics of ion channels as selectivity, activation mechanism, and intracellular and tissue localization, those ion channels that meet the requirements for potential participation in ES generation were selected from a wide variety of ion channels in higher plants. Analysis of the data of experimental studies performed on mutants with suppressed or enhanced expression of a certain channel gene revealed those channels whose activation contributes to ESs formation. The channels responsible for Ca2+ flux during generation of ESs include channels of the GLR family, for K+ flux - GORK, for anions - MSL. Consideration of the prospects of further studies suggests the need to combine electrophysiological and genetic approaches along with analysis of ion concentrations in intact plants within a single study.

Extremely low-frequency magnetic fields are thought to be capable of modulating the resistance of plants to adverse factors, particularly drought. Magnetic fields in this frequency range occur in nature in connection with so-called Schumann resonances, excited by lightning discharges in the Earth-ionosphere cavity. The aim of this work was to identify the influence of a magnetic field with a frequency of 14.3 Hz (which corresponds to the second Schumann harmonic) on the transpiration and photosynthesis of wheat plants under the influence of drought. The activity of photosynthesis processes, the crop water stress index, relative water content and leaf area were determined during drought intensification. At the end of the experiment, on the 12th day of drought, the length, and fresh and dry weight of wheat shoots were measured. The results obtained indicate a protective effect of the magnetic field on plants in unfavorable drought conditions; the magnetic field delayed the development of harmful changes in the transpiration and photosynthesis processes for several days. At the same time, in the absence of the stressor (drought), the effect of the electromagnetic field was not detected, except for a decrease in relative transpiration. In favorable conditions, there were only minimal modifications of the photosynthetic processes and transpiration by the magnetic field.

In the natural fluidic environment of a biological system, nanoparticles swiftly adsorb plasma proteins on their surface forming a "protein corona", which profoundly and often adversely affects their residence in the systemic circulation in vivo and their interaction with cells in vitro. It has been recognized that preformation of a protein corona under controlled conditions ameliorates the protein corona effects, including colloidal stability in serum solutions. We report on the investigation of the stabilizing effects of a denatured bovine serum albumin (dBSA) protein corona formed on the surface of upconversion nanoparticles (UCNPs). UCNPs were chosen as a nanoparticle model due to their unique photoluminescent properties suitable for background-free biological imaging and sensing. UCNP surface was modified with nitrosonium tetrafluoroborate (NOBF 4 ) to render it hydrophilic. UCNP-NOBF 4 nanoparticles were incubated in dBSA solution to form a dBSA corona followed up by lyophilization. As produced dBSA-UCNP-NOBF 4 demonstrated high photoluminescence brightness, sustained colloidal stability after long-term storage and the reduced level of serum protein surface adsorption. These results show promise of dBSA-based nanoparticle pretreatment to improve the amiability to biological environments towards theranostic applications.

To convert and store energy in the process of photosynthesis, plants primarily use quanta of the red and blue parts of the spectrum. At high latitudes, the average daily intensity of red and blue parts of the spectrum is not very high; for many crops cultivated under greenhouse conditions, it reaches the sufficient level only on clear summer days. The problem of insufficient illumination in greenhouses is usually solved with artificial light sources. This article describes a technology for the manufacture of photoconversion fluoropolymer films for greenhouses. The fluoropolymer films described in the paper make use of original gold nanoparticles and nanoparticles with fluorescence in the blue or red region of the spectrum. In the polymer film, nanoparticles aggregate in the form of "beads", which enhances the field of the optical wave. The film photoconverts UV and violet light into blue and red light. Gold nanoparticles also partially convert energy in the green region of the spectrum (not used by plants) into heat, which is also important for agriculture at high latitudes. In addition, impregnation of gold nanoparticles into fluoropolymer significantly increases the lifetime of the film. The films described in the paper can significantly increase the productivity of greenhouses located at high latitudes. Plants cultivated under the films have more chlorophyll and a higher intensity of photosynthesis - although their system of distance stress signals is, to a certain degree, suppressed., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The synergy problem was discussed linking Se nanoparticles and different soil fertility agents. Se zero-valent-state nanoparticles were investigated as fertilizers and antioxidants. A technology was proposed for producing Se zero-valent-state nanoparticles. Se nanoparticles were obtained by laser ablation of Se in water using a fiber ytterbium laser, with a wavelength between 1060 and 1070 nm, a pulse repetition rate of 20 kHz, a pulse duration of 80 ns, and an average power of 20 W, and a copper vapor laser with wavelengths of 510.6 and 578.2 nm and an average power of 8 W. The main particle mass part shifted from 800 nm to a size less than 100 nm, corresponding to the increase in the laser fragmentation time. The resulting nanoparticles were monodisperse in size and mass. The Se nanoparticle water suspension was introduced into the soil. The soil Se nanoparticle concentrations were about 1, 5, 10, and 25 μg kg -1 . An experiment was carried out in a climate chamber in two series: (1) growing plants in soil imitating the standard organogenesis environment conditions such as illumination of 16 h per day, temperature of 22 °C, soil humidity of 25% SDW, and an experiment duration of 30 days and (2) growing plants in soil under changing environmental conditions of organogenesis. The standard environmental conditions for the first 10 days are illumination of 16 h day -1 , temperature of 22 °C, and soil humidity of 25% SDW. The plant stress for 5 days is hyperthermia of 40 °C. The standard environmental conditions for the next 15 days are illumination of 16 h day -1 , temperature of 22 °C, and soil humidity of 25% SDW. At standard organogenesis, the plant leaf plate surface area was 30 ± 2 cm 2 in the control option, and the Se nanoparticle doses were correspondingly 1 μg kg -1 for 32 ± 3 cm 2 , 5 μg kg -1 for 37 ± 2 cm 2 , 10 μg kg -1 for 38 ± 3 cm 2 , and 25 μg kg -1 for 28 ± 4 cm 2 . Hyperthermia stressed plant growth was studied. The highest plant growth rate was in Se nanoparticle concentrations of 5 and 10 μg kg -1 . The eggplant growth on the soil with the Se nanoparticle addition at a concentration of 10 μg kg -1 of leaf plate surface area was twice compared to the eggplant growth in untreated soil. The same was for tomato plants. The leaf plate surface area of the cucumber plant grown using Se nanoparticles was 50% higher compared to the control option. The Biogeosystem technique methodology of 20-45 cm soil-layer intrasoil milling for soil multilevel aggregate system formation and intrasoil pulse continuous-discrete watering for soil water regime control was proposed for the Se nanoparticles for better function in the real soil, providing a synergy effect of soil mechanical processing, nanoparticles, humic substances, and polymicrobial biofilms on soil fertility., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Upconversion nanoparticles (UCNPs) are new-generation photoluminescent nanomaterials gaining considerable recognition in the life sciences due to their unique optical properties that allow high-contrast imaging in cells and tissues. Upconversion nanoparticle applications in optical diagnosis, bioassays, therapeutics, photodynamic therapy, drug delivery, and light-controlled release of drugs are promising, demanding a comprehensive systematic study of their pharmacological properties. We report on production of biofunctional UCNP-based nanocomplexes suitable for optical microscopy and imaging of HER2-positive cells and tumors, as well as on the comprehensive evaluation of their pharmacokinetics, pharmacodynamics, and toxicological properties using cells and laboratory animals. The nanocomplexes represent a UCNP core/shell structure of the NaYF4:Yb, Er, Tm/NaYF4 composition coated with an amphiphilic alternating copolymer of maleic anhydride with 1-octadecene (PMAO) and conjugated to the Designed Ankyrin Repeat Protein (DARPin 9_29) with high affinity to the HER2 receptor. We demonstrated the specific binding of UCNP-PMAO-DARPin to HER2-positive cancer cells in cultures and xenograft animal models allowing the tumor visualization for at least 24 h. An exhaustive study of the general and specific toxicity of UCNP-PMAO-DARPin including the evaluation of their allergenic, immunotoxic, and reprotoxic properties was carried out. The obtained experimental body of evidence leads to a conclusion that UCNP-PMAO and UCNP-PMAO-DARPin are functional, noncytotoxic, biocompatible, and safe for imaging applications in cells, small animals, and prospective clinical applications of image-guided surgery., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Carcinomas overexpressing EGFR family receptors are of high clinical importance, because the receptors have prognostic value and are used as molecular targets for anticancer therapy. Insufficient drug efficacy necessitates further in-depth research of the receptor biology and improvement in preclinical stages of drug evaluation. Here, we review the currently used advanced 3D in vitro models of tumors, including tumor spheroids, models in natural and synthetic matrices, tumor organoids and microfluidic-based models, as a potent tool for studying EGFR biology and targeted drug development. We are especially focused on factors that affect the biology of tumor cells, causing modification in the expression and basic phosphorylation of the receptors, crosstalk with other signaling pathways and switch between downstream cascades, resulting ultimately in the resistance to antitumor agents., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

We report combined therapy using upconversion nanoparticles (UCNP) coupled to two therapeutic agents: beta-emitting radionuclide yttrium-90 ( 90 Y) fractionally substituting yttrium in UCNP, and a fragment of the exotoxin A derived from Pseudomonas aeruginosa genetically fused with a targeting designed ankyrin repeat protein (DARPin) specific to HER2 receptors. The resultant hybrid complex UCNP-R-T was tested using human breast adenocarcinoma cells SK-BR-3 overexpressing HER2 receptors and immunodeficient mice, bearing HER2-positive xenograft tumors. The photophysical properties of UCNPs enabled background-free imaging of the UCNP-R-T distribution in cells and animals. Specific binding and uptake of UCNP complexes in SK-BR-3 cells was observed, with separate 90 Y- and PE40-induced cytotoxic effects characterized by IC 50 140 μg/mL (UCNP-R) and 5.2 μg/mL (UCNP-T), respectively. When both therapeutic agents were combined into UCNP-R-T, the synergetic effect increased markedly, ∼2200-fold, resulting in IC 50 = 0.0024 μg/mL. The combined therapy with UCNP-R-T was demonstrated in vivo., Competing Interests: The authors declare no conflict of interest.

Tetra(aryl)tetracyanoporphyrazines are the promising group of dyes for photodynamic therapy of tumors with unique combination of photosensitizer properties and sensitivity of fluorescence parameters to the environment viscosity. However, in vivo application of such hydrophobic photosensitizers requires using of drug carriers ensuring efficient delivery to the tumor site. The present study is focused on obtaining liposomes loaded with tetrakis(4-benzyloxyphenyl)tetracyanoporphyrazine and examining their properties depending on lipid composition. An efficient loading of the dye and a high long-term stability were proved for the liposomes composed of phosphatidylcholine with cholesterol and phosphatidylglycerol. This can be explained by the presence of negatively charged lipids in the bilayer and, as a consequence, a high value of the surface potential. A high rate of cellular uptake and a strong photoinduced toxicity give the prerequisites for the further use of the liposomal form of the photosensitizer for photodynamic therapy of tumors.

Efficient drug delivery can be assigned to tasks that attract the most acute attention of researchers in the field of anticancer drug design. We have reported the first case of using amphiphilic polymer brushes as nanocontainers for photosensitizer delivery to cancer cells. Regular graft-copolymers of hydrophobic polyimides with hydrophilic polymethacrylic acid side chains were loaded with photosensitive dye tetra(4-fluorophenyl)tetracyanoporphyrazine (Pz) providing a sufficiently stable homogeneous fraction of fluorescent Pz-loaded nanoparticles with a size of 100-150 nm. Pz-loaded polymer brushes were substantially more efficient for Pz delivery into cells compared with other types of particles examined, Pz-polyethyleneglycol and Pz-methylcellulose. In vivo, an efficient Pz delivery to tumor can also be expected since the Pz-PB particle size is in the optimal range for passive targeting. Pz-PB showed pronounced photodynamic activity, while, that is important, in the absence of irradiation the PB carrier itself was significantly less toxic than the dye itself. Summing up, water-soluble polymer brushes with polyimide backbones and polymethacrylic acid side chains can be regarded as a novel type of nanocontainers providing efficient intracellular drug delivery for photodynamic therapy of cancers., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Targeted radionuclide therapy is one of the most intensively developing directions of nuclear medicine. Unlike conventional external beam therapy, the targeted radionuclide therapy causes less collateral damage to normal tissues and allows targeted drug delivery to a clinically diagnosed neoplastic malformations, as well as metastasized cells and cellular clusters, thus providing systemic therapy of cancer. The methods of targeted radionuclide therapy are based on the use of molecular carriers of radionuclides with high affinity to antigens on the surface of tumor cells. The potential of targeted radionuclide therapy has markedly grown nowadays due to the expanded knowledge base in cancer biology, bioengineering, and radiochemistry. In this review, progress in the radionuclide therapy of hematological malignancies and approaches for treatment of solid tumors is addressed.

Electrical signals presented in plants by action potential and by variation potential (VP) can induce a reversible inactivation of photosynthesis. Changes in the intracellular and extracellular pH during VP generation are a potential mechanism of photosynthetic response induction; however, this hypothesis requires additional experimental investigation. The purpose of the present work was to analyze the influence of pH changes on induction of the photosynthetic response in pumpkin. It was shown that a burning of the cotyledon induced VP propagation into true leaves of pumpkin seedlings inducing a decrease in the photosynthetic CO2 assimilation and an increase in non-photochemical quenching of fluorescence, whereas respiration was activated insignificantly. The photosynthetic response magnitude depended linearly on the VP amplitude. The intracellular and extracellular concentrations of protons were analyzed using pH-sensitive fluorescent probes, and the VP generation was shown to be accompanied by apoplast alkalization (0.4 pH unit) and cytoplasm acidification (0.3 pH unit). The influence of changes in the incubation medium pH on the non-photochemical quenching of fluorescence of isolated chloroplasts was also investigated. It was found that acidification of the medium stimulated the non-photochemical quenching, and the magnitude of this increase depended on the decrease in pH. Our results confirm the contribution of changes in intracellular and extracellular pH to induction of the photosynthetic response caused by VP. Possible mechanisms of the influence of pH changes on photosynthesis are discussed.

The influence of a variation potential on photosynthesis in pumpkin seedlings (Cucurbita pepo L.) was investigated in our work. It was shown that the variation potential induced by cotyledon burning propagates into a leaf. It decreases CO2 assimilation and transpiration as well as increases nonphotochemical quenching. Investigation of isolated chloroplasts showed that lowering of the pH in incubation medium from 6.9-7.2 to 6.5 increases nonphotochemical quenching. It was proposed that lowering of the cytoplasmic pH induced by the variation potential takes place in the photosynthetic response development.

Confocal microscopy technique was applied for registration of apoplast pH changes in the Cucurbita pepo seedling stem during generation of action potential and variation potential. Fluorescent dye FITC-dextran was used for pH-changes registration. Analysis of fluorescence images and fluorescence spectra showed, that FITC-dextran was localized in cell walls. Propagation of action potential and variation potential was accompanied by transient increase of fluorescence intensity, which indicated alkalization of cell walls. This transient alkalization is proposed to be caused by a temporary inactivation of the H(+)-pump in the plasma membrane.

As was shown recently the generation of cooling-induced action potential accompanies the reversible change of extracellular pH.1 The pH changes are linked to the Ca(2+)-induced transient inhibition of the plasma membrane H(+)-ATPase. Generation of mechano-induced local bioelectrical reaction (LBER) also accompanies the reversible change of extracellular pH. Shifts of pH medium during generation of mechano-induced electrical impulse are less than during generation of cooling-induced bioelectrical response. The exclusion of Ca(2+) influx from extracellular stores don't decrease the amplitude of mechano-induced LBER.

The presence of strongly pronounced metabolic dependence of cooling-induced action potentials (APs) in excitable cells of pumpkin stem was shown using NaN3, DCCD, and IAA. This dependence might be connected with participation of the plasma-membrane ATP-dependent pump in the excitation process. The decrease of extracellular Ca2+ concentration had as strong depressive effect on the AP as that of the inhibition of metabolism. It has been supposed that the calcium signal is important coupling factor between the AP generation and the metabolism of excitable cells.