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IntroductionSmall membrane particles called extracellular vesicles (EVs) transport biologically active cargo between cells, providing intercellular communication. The clinical application of EVs is limited due to the lack of scalable and cost-effective approaches for their production and purification, as well as effective loading strategies.MethodsHere we used EV mimetics produced by cell treatment with the actin-destabilizing agent cytochalasin B as an alternative to EVs for the delivery of therapeutic nucleic acids.ResultsCytochalasin-B-inducible nanovesicles (CINVs) delivered a fully modified N-(methanesulfonyl)- or mesyl (µ-) antisense oligonucleotide to B16 melanoma cells, selectively decreasing the level of target microRNA-21 with effectiveness comparable to that observed upon Lipofectamine 2000-mediated delivery. The efficiency of the CINV-mediated delivery of plasmid DNA encoding EGFP varied depending on the type of recipient cells. Surprisingly, under experimental conditions, CINVs were unable to deliver both modified and natural short RNA duplexes—small interfering RNA and immunostimulatory RNA—probably due to their poor loading into CINVs.DiscussionCINVs demonstrated unique properties for the delivery of therapeutic nucleic acids, especially for antisense oligonucleotide-based therapy.

We present a theory describing the interaction of structured light, such as light carrying orbital angular momentum, with molecules. The light-matter interaction Hamiltonian we derive is expressed through couplings between spherical gradients of the electric field and the (transition) electric multipole moments of a particle of any nontrivial rotation point group. Our model can therefore accommodate an arbitrary complexity of the molecular and electric field structure, and it can be straightforwardly extended to atoms or nanostructures. Applying this framework to rovibrational spectroscopy of molecules, we uncover the general mechanism of angular momentum exchange between the spin and orbital angular momenta of light, molecular rotation, and its center-of-mass motion. We show that the nonzero vorticity of Laguerre-Gaussian beams can strongly enhance certain rovibrational transitions that are considered forbidden in the case of nonhelical light. We discuss the experimental requirements for the observation of these forbidden transitions in state-of-the-art spatially resolved spectroscopy measurements.

Earthworms play a vital role in the terrestrial ecosystem functioning and maintenance of soil fertility. However, many pesticides, for example, imidacloprid, benomyl, and metribuzin that are world-widely used in agriculture, may be potentially dangerous to earthworms. At the same time, standard tests for pesticides acute and chronic toxicity do not reflect all aspects of their negative impact and might not be enough sensitive for effective assessment. In this paper, we studied the effects of non-lethal concentrations of imidacloprid, benomyl, and metribuzin on the gut bacterial community of Lumbricus terrestris using high-throughput sequencing approach. We found that pesticides reduced the total bacterial diversity in the earthworm’s gut even at the recommended application rate. Under the applied pesticides, the structure of the gut prokaryotic community underwent changes in the relative abundance of the phyla Proteobacteria, Actinobacteria, Acidobacteria, Planctomyces, Verrucomicrobia, and Cyanobacteria, as well as the genera Haliangium, Gaiella, Paenisporosarcina, Oryzihumus, Candidatus Udaeobacter, and Aquisphaera. Moreover, the pesticides affected the abundance of Verminephrobacter—the earthworms’ nephridia specific symbionts. In general, the negative impact of pesticides on bacterial biodiversity was significant even under pesticides content, which was much lower than their acute and chronic toxicity values for the earthworms. These results highlighted the fact that the earthworm’s gut microbial community is highly sensitive to soil contamination with pesticides. Therefore, such examination should be considered in the pesticide risk assessment protocols.

The effect of spacer layers on electron transport through two-barrier nanostructures was studied using the numerical solution of the time-dependent Schrodinger–Poisson equations with exact discrete open boundary conditions. The formulation of the problem took into account both the active region consisting of a quantum well and barriers, as well as the presence of highly doped contact layers and spacer layers. The use of the time formulation of the problem avoids the divergence of the numerical solution, which is usually observed when solving a stationary system of the Schrodinger–Poisson equations at small sizes of spacer layers. It is shown that an increase in the thickness of the emitter spacer leads to a decrease in the peak current through the resonant tunneling nanostructures. This is due to the charge accumulation effects, which, in particular, lead to a change in the potential in an additional quantum well formed in the emitter spacer region when a constant electric field is applied. The valley current also decreases as the thickness of the emitter spacer increases. The peak current and valley current are weakly dependent on the thickness of the collector spacer. The collector spacer thickness has a strong effect on the applied peak and valley voltages. The above features are valid for all three different resonant tunneling nanostructures considered in this study. For the RTD structures based on Al0.3Ga0.7As/GaAs, the optimized peak current value Ipmax = 5.6 × 109 A/m2 and the corresponding applied voltage Vp = 0.44 V. For the RTD structures based on AlAs/In0.8Ga0.2As, Ipmax = 14.5 × 109 A/m2 (Vp = 0.54 V); for RTD structures based on AlAs/In0.53Ga0.47As, Ipmax = 45.5 × 109 A/m2 (Vp = 1.75 V).

JET experiments using the fuel mixture envisaged for fusion power plants, deuterium and tritium (D–T), provide a unique opportunity to validate existing D–T fusion power prediction capabilities in support of future device design and operation preparation. The 2021 JET D–T experimental campaign has achieved D–T fusion powers sustained over 5 s in ITER-relevant conditions i.e. operation with the baseline or hybrid scenario in the full metallic wall. In preparation of the 2021 JET D–T experimental campaign, extensive D–T predictive modelling was carried out with several assumptions based on D discharges. To improve the validity of ITER D–T predictive modelling in the future, it is important to use the input data measured from 2021 JET D–T discharges in the present core predictive modelling, and to specify the accuracy of the D–T fusion power prediction in comparison with the experiments. This paper reports on the validation of the core integrated modelling with TRANSP, JINTRAC, and ETS coupled with a quasilinear turbulent transport model (Trapped Gyro Landau Fluid or QualLiKiz) against the measured data in 2021 JET D–T discharges. Detailed simulation settings and the heating and transport models used are described. The D–T fusion power calculated with the interpretive TRANSP runs for 38 D–T discharges (12 baseline and 26 hybrid discharges) reproduced the measured values within 20 $\%$ . This indicates the additional uncertainties, that could result from the measurement error bars in kinetic profiles, impurity contents and neutron rates, and also from the beam-thermal fusion reaction modelling, are less than $20\%$ in total. The good statistical agreement confirms that we have the capability to accurately calculate the D–T fusion power if correct kinetic profiles are predicted, and indicates that any larger deviation of the D–T fusion power prediction from the measured fusion power could be attributed to the deviation of the predicted kinetic profiles from the measured kinetic profiles in these plasma scenarios. Without any posterior adjustment of the simulation settings, the ratio of predicted D–T fusion power to the measured fusion power was found as 65%–96% for the D–T baseline and 81%–97% for D–T hybrid discharge. Possible reasons for the lower D–T prediction are discussed and future works to improve the fusion power prediction capability are suggested. The D–T predictive modelling results have also been compared to the predictive modelling of the counterpart D discharges, where the key engineering parameters are similar. Features in the predicted kinetic profiles of D–T discharges such as underprediction of n _e are also found in the prediction results of the counterpart D discharges, and it leads to similar levels of the normalized neutron rate prediction between the modelling results of D–T and the counterpart D discharges. This implies that the credibility of D–T fusion power prediction could be a priori estimated by the prediction quality of the preparatory D discharges, which will be attempted before actual D–T experiments.

The term “people's quality of life” has not been given any widespread explanation in the context of society digital transformation. There are six attributes specified to characterize digital component of people's quality of life. Basing on official statistics data, subindices for the corresponding data blocks were computed. A mixed method to estimate the digital component of people's quality of life was used. Also, the Russian index of digital component of people's quality of life was defined for the whole country and for its federal districts. The results of computations allowed to characterize the changes in subindices within blocks and in the integral index covering eight federal districts and in Russia in the whole for the period of 2015–2017. Positive dynamics of the Russian index of digital component of people's quality of life was revealed with some fluctuations for different federal districts.

The design of cationic liposomes for efficient mRNA delivery can significantly improve mRNA-based therapies. Lipoplexes based on polycationic lipid 1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetraazahexacosane tetrahydrochloride (2X3) and helper lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) were formulated in different molar ratios (1:1, 1:2, 1:3) to efficiently deliver model mRNAs to BHK-21 and A549. The objective of this study was to examine the effect of 2X3-DOPE composition as well as lipid-to-mRNA ratio (amino-to-phosphate group ratio, N/P) on mRNA transfection. We found that lipoplex-mediated transfection efficiency depends on both liposome composition and the N/P ratio. Lipoplexes with an N/P ratio of 10/1 showed nanometric hydrodynamic size, positive ζ potential, maximum loading, and transfection efficiency. Liposomes 2X3-DOPE (1:3) provided the superior delivery of both mRNA coding firefly luciferase and mRNA-eGFP into BHK-21 cells and A549 cells, compared with commercial Lipofectamine MessengerMax.

Agriculture is the main contributor to nitrous oxide (N2O) emission, but the emission intensity can be controlled by various factors, in particular, the activity of earthworms, one of the most common groups of soil invertebrates. We conducted an incubation experiment to evaluate N2O emission in earthworm soil samples compared to non-earthworm ones with applications of high (200 kg ha−1) and low (50 kg ha−1) mineral N fertilizer doses. We assessed the cumulative N2O emission, the dynamics of the soil dissolved organic carbon, and the soil microbial carbon and nitrogen content, as well as the number of nirK and nirS gene copies in bulk soil samples and in isolates from the earthworms’ gut. Our study showed a significant role of the earthworm activity in changing the intensity of N2O emission after the application of mineral N fertilizers. The main factor leading to an increase in nitrous oxide emission in the presence of earthworms is the stimulation of free-living soil denitrifiers by the organic matter of the earthworms’ excretions, as well as the thorough mixing of plant residues and soil. Contrary to our expectations, earthworms did not increase the representation of nitrite reductase genes in soil, although the earthworm’s gut can be considered as a refugium for denitrifiers. Our results indicate a possible risk of increased N2O emission from arable temperate soils with an increase in earthworm populations as the climate warms, even if application rates of mineral fertilizers are reduced.

Natural polyamines (PAs) are involved in the processes of proliferation and differentiation of cancer cells. Lipophilic synthetic polyamines (LPAs) induce the cell death of various cancer cell lines. In the current paper, we have demonstrated a new method for synthesis of LPAs via the multicomponent Ugi reaction and subsequent reduction of amide groups by PhSiH3. The anticancer activity of the obtained compounds was evaluated in the A-549, MCF7, and HCT116 cancer cell lines. For the first time, it was shown that the anticancer activity of LPAs with piperazine fragments is comparable with that of aliphatic LPAs. The presence of a diglyceride fragment in the structure of LPAs appears to be a key factor for the manifestation of high anticancer activity. The findings of the study strongly support further research in the field of LPAs and their derivatives.

We study an impurity with a resonance level whose position coincides with the Fermi energy of the surrounding Fermi gas. An impurity causes a rapid variation of the scattering phase shift for fermions at the Fermi surface, introducing a new characteristic length scale into the problem. We investigate manifestations of this length scale in the self-energy of the impurity and in the density of the bath. Our calculations reveal a model-independent deformation of the density of the Fermi gas, which is determined by the width of the resonance. To provide a broader picture, we investigate time evolution of the density in quench dynamics, and study the behavior of the system at finite temperatures. Finally, we briefly discuss implications of our findings for the Fermi-polaron problem.

Biogenic polyamines (PAs) are involved in the growth and development of normal cells, and their intracellular concentration is stable. The concentration of PAs in cancer cells is significantly increased to promote and sustain their rapid proliferation. Over the years, synthetic PAs, which differ in their structure, have demonstrated high antitumor activity and are involved in clinical trials. The chemical synthesis of PAs and their conjugates require the correct choice of synthetic pathways—methods for constructing conjugates and the orthogonal protection of amino groups. The most common methods of synthesis of PA conjugates are acylation of regioselectively protected PAs or their alkylation under the conditions of the Fukuyama reaction. One of the most promising methods of PA synthesis is the use of a multicomponent Ugi reaction, which allows various PAs to be obtained in high yields. In this review, we describe and analyze various approaches that are used in the synthesis of polyamines and their conjugates.

There are many approaches of pesticide risk assessment. Despite their variation in difficulty and information complexity, all of them are intended to predict the actual pesticide risk as accurately as possible, i.e., to predict the behavior and hazard of a pesticide in the environment with high precision. The aim of this study was to develop a risk indicator of pesticide’s negative impact on soil and aquatic organisms. The developed pesticide risk indicator constitutes the sum of points of acute toxicity exposure ratio, long-term toxicity exposure ratio, and the bioconcentration factor. To develop the indicator, mathematical models were used; the input data included the soil and climate conditions of a specific region. Combining the data of pesticide toxicity in the environment allowed for a more accurate risk assessment in terms of using plant protection products. The toxicity and behavior in soil and water of 200 widespread pesticides were studied. It could be concluded that a mathematical model, PEARL 4.4.4, calibrated for region-specific soil-climate conditions, provides a relevant description of the natural translocation and decomposition of pesticides in soils. In addition, the output data of this model can be applied to calculate the risk indicators. The combination of these parameters with pesticide toxicity for non-target groups of organisms allows the risk indicator to be a universal tool for predicting the negative impact of pesticides on the environment at the regional level.

Quantum–chemical calculations of the electronic characteristics of carbon and boron-doped silicon polyprismanes were carried out, and the atomic hydrogen adsorption on these structures was analyzed. It was established that silicon polyprismanes doped with boron and carbon retained their metallicity predicted earlier. It was shown that the doping of polyprismanes made them more thermodynamically stable. For the silicon prismanes doped with boron or carbon, hydrogen adsorption was found to be energetically favorable. In the case of boron-doped prismanes, adsorption on the boron impurity was much more advantageous than on the neighboring silicon nodes. For the carbon doping, the adsorption energy of polyprismane with a small diameter weakly depended on the position of the hydrogen atom near the impurity center. However, for the C-doped polyprismanes with a larger diameter, the hydrogen adsorption on the silicon atom belonging to the ring with impurity is more energetically favorable than the adsorption on the silicon atom from the adjacent ring.

Silicene is considered to be the most promising anode material for lithium-ion batteries. In this work, we show that transmutation doping makes silicene substantially more suitable for use as an anode material. Pristine and modified bilayer silicene was simulated on a graphite substrate using the classical molecular dynamics method. The parameters of Morse potentials for alloying elements were determined using quantum mechanical calculations. The main advantage of modified silicene is its low deformability during lithium intercalation and its possibility of obtaining a significantly higher battery charge capacity. Horizontal and vertical profiles of the density of lithium as well as distributions of the most significant stresses in the walls of the channels were calculated both in undoped and doped systems with different gaps in silicene channels. The energies of lithium adsorption on silicene, including phosphorus-doped silicene, were determined. High values of the self-diffusion coefficient of lithium atoms in the silicene channels were obtained, which ensured a high cycling rate. The calculations showed that such doping increased the normal stress on the walls of the channel filled with lithium to 67% but did not provoke a loss of mechanical strength. In addition, doping achieved a greater battery capacity and higher charging/discharging rates.

The performance of cationic liposomes for delivery of therapeutic nucleic acids in vivo can be improved and specifically tailored to certain types of cargo and target cells by incorporation of PEG-containing lipoconjugates in the cationic liposome’s composition. Here, we report on the synthesis of novel PEG-containing lipoconjugates with molecular masses of PEG 800, 1500 and 2000 Da. PEG-containing lipoconjugates were used as one of the components in liposome preparation with the polycationic amphiphile 1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetra-azahexacosan tetrahydrochloride (2X3) and the lipid-helper dioleoylphosphatidylethanolamine (DOPE). We demonstrate that increasing the length of the PEG chain reduces the transfection activity of liposomes in vitro, but improves the biodistribution, increases the circulation time in the bloodstream and enhances the interferon-inducing activity of immunostimulating RNA in vivo.

Book review: Boris N. Mironov: Istoricheskaia sotsiologiia Rossii. Sankt-Peterburg: Intersocis, 2009, 536 pp.

The article discusses political processes in post-Soviet Russia from the perspective of the multiple modernities theory. A study of Russia’s political transformation on the basis of this approach allows us to reconsider the obstacles to democratization that existed in the 1990s and the socio-cultural preconditions for de-democratization in the 2000s. The author draws on Johann Arnason’s analysis of the Soviet model of modernity. From this perspective the Soviet model possessed only some civilizational traits and did not lead to a sustainable civilizational pattern. Nevertheless, remnants of that model and the imperial legacy of the Soviet period influenced Russian politics of the last two decades. The dynamics of democratization and de-democratization in Russia represent a case of path dependency which is both post-communist and post-imperial.