Anti-cancer activity of ultra-short single-stranded polydeoxyribonucleotides.

One of the features that differentiate cancer cells is their increased proliferation rate, which creates an opportunity for general anti-tumor therapy directed against the elevated activity of replicative apparatus in tumor cells. Besides DNA synthesis, successful genome replication requires the reparation of the newly synthesized DNA. Malfunctions in reparation can cause fatal injuries in the genome and cell death. Recently we have found that the ultra-short single-stranded deoxyribose polynucleotides of random sequence (ssDNA) effectively inhibit the catalytic activity of DNA polymerase [Formula: see text]. This effect allowed considering these substances as potential anti-tumor drugs, which was confirmed experimentally both in vitro (using cancer cell cultures) and in vivo (using cancer models in mice). According to the obtained results, ssDNA significantly suppresses cancer development and tumor growth, allowing consideration of them as novel candidates for anti-cancer drugs.

Triggering gel-sol transition by weak magnetic field.

The self-assembly of small and always chiral molecules into fiber-like structures is a mysterious process, as the physics underlying such self-assembly is unclear. The energy necessary for this process exceeds the one provided by common dispersion interactions and hydrogen bonding. The recent results obtained by the scientific group of Prof. Naaman from the Weizmann Institute of Science fed light on the nature of forces providing for the self-assembly of chiral molecules and attributed these forces to spin-exchange interactions. Therefore, the self-assembly of chiral molecules should be magneto-sensitive. We found such sensitivity in solutions of trifluoroacetylated α -amino alcohols, and the process was inhibited by the magnetic field when fibers grew on the surface of the substrate. On the contrary, in bulk, the self-assembly was enhanced by the magnetic field and led to the formation of a dense gel, while no gelation was observed in the absence of the external magnetic field. The latter observations are the theme of this short report, aimed to declare the effect itself but not pretend to describe it in full.

A gel lattice alters the phase state of a solvent.

Some low-molecular-weight substances are able to self-assemble into fiber-like structures (strings) to form gels. One of the examples of such substances is trifluoroacetylated alpha-aminoalcohols (TFAAAs) able to gelate in many organic solvents. Here we report the formation and describe the properties of a layer of an altered solvent covering the strings' surface. The altered solvent layer has a different refractive index and melts at a temperature about several degrees lower than that of the bulk solvent. Moreover, the bulk solvent's melting temperature was also decreased by values far beyond the one expected according to Raoult's law. Based on the Gibbs-Thomson equation it is possible to derive the thickness of the special layer as well as the average gel lattice parameters, which were very stable across the variety of systems investigated.

The role of exchange interactions in the stability of cellulose.

The problem of the origin of biochirality and the related problem of the initial monomer selection are still under discussion, and the main point here is not the mechanics of enantiomer separation but the problem of the role of chirality in the very early stages of evolution. A recent breakthrough in understanding the influence of a static magnetic field on non-magnetic systems can shed light on this complex problem. The phenomenon of magnetosensitivity of non-magnetic systems was reported for only chiral systems and was closely related to the ability of some chiral substances to self-assemble. We suppose the chirality was essential due to the quantum spin-related effects arising between the interacting chiral molecules and providing for the self-assembly phenomenon. Here we demonstrate the magnetosensitivity of the supramolecular packing of cellulose chains, directly indicating the reliability of the supposition above.

Molecular Self-Assembly as a Trigger of Life Origin and Development.

The origin and reason for the homochirality of living cells go with the problem of a relatively narrow spectrum of the actual biological monomers compared to the whole theoretically possible spectrum of amino acids or carbohydrates. A limited number of bio-monomers implies some special feature differing from all other similar molecules that are not present in the living cell. Here we propose one of the candidates for such a peculiarity: the ability to form highly elongated helical supramolecular structures (strings) when precipitating from homochiral solutions. The strings' forming can be accompanied by spontaneous splitting and/or chiral purification of the initially racemic mixture. Our previous theoretical reasoning was based mainly on the biomimetic systems, while now we describe the strings forming in homochiral amino acid solutions.

On the mechanism of effectively chiral-pure macromolecular spiralization induced by a weakly chiral polarized heterochiral solution of a chiral compound.

There has been made an assumption, correlating with experimental data, that the phenomenon of effectively chiral-pure, chiral-induced spiralization of macromolecules in weakly polarized heterochiral solutions is determined by the mechanism of physico-chemical annihilation: enantiomers-antipodes of a chiral compound in a heterochiral solution annihilate; that is, they form achiral dimers, the solution becomes effectively homochiral and further, chiral-induced macromolecular spiralization of one sign of helicity is realized in it in the same way as in other homochiral solutions.

Chirality Driven Twisting as a Driving Force of Primitive Folding in Binary Mixtures.

The N-trifluoroacetylated α-aminoalcohols (TFAAAs) are able to form quasi-one-dimensional supramolecular fibers (strings) when chirally pure, and isometric precipitates in the racemate. The strings' formation leads to the reversible gelation of the solution. The fresh gels occupy all the available volume, however during the incubation, they contract and concentrate in the central region of the tube. The microscopic observations revealed the growth of the strings' diameter and their rotation in the course of the incubation at the hour time-scale. The rotation provides for the hairpins forming that serve as hooks on the rotating string, which provides for coiling of the strings, which was observed as gel contraction. The morphology of the twisted strings resembles the structures observed in modern proteins, which allows drawing an analogy between the folding of biopolymers and the formation of the clew of strings. In addition, the rotation found in the TFAAA gels is an example of a simple system converting the energy of intermolecular agglutination to the rotational movement, so they could be considered as molecular motors.

Spontaneous Resolution and Super-coiling in Xerogels of the Products of Photo-Induced Formose Reaction.

This work addresses the supramolecular self-organization in the xerogels of formose reaction products. The UV-induced formose reaction was held in over-saturated formaldehyde solutions at 70∘C without a catalyst. The solutions of the obtained carbohydrates were dried on a glass slide, and the obtained xerogels demonstrated a prominent optical activity, while the initial solutions were optically inactive. The xerogels contained highly elongated crystalline elements of a helical structure as well as the isometric ones. Thus xerogel formation was accompanied by a spontaneous resolution of enantiomers and separation of different-shaped supramolecular structures. The thick helices were twisted of thinner ones, while the latter were twisted of elementary structures having a diameter much smaller than 400 nm. Similar structural hierarchy is typical of biological macromolecules (DNA, proteins, and cellulose). Summarizing the obtained results, we proposed a hypothetical mechanism explaining the amplification of the initial enantiomeric excess, as well as chiral and chemical purification of the substances which were essential for the evolution of Life to start.

Magnetic field and nuclear spin influence on the DNA synthesis rate.

The rate of a chemical reaction can be sensitive to the isotope composition of the reactants, which provides also for the sensitivity of such "spin-sensitive" reactions to the external magnetic field. Here we demonstrate the effect of the external magnetic field on the enzymatic DNA synthesis together with the effect of the spin-bearing magnesium ions ([Formula: see text]Mg). The rate of DNA synthesis monotonously decreased with the external magnetic field induction increasing in presence of zero-spin magnesium ions ([Formula: see text]Mg). On the contrary, in the presence of the spin-bearing magnesium ions, the dependence of the reaction rate on the magnetic field induction was non-monotonous and possess a distinct minimum at 80-100 mT. To describe the observed effect, we suggested a chemical scheme and biophysical mechanism considering a competition between Zeeman and Fermi interactions in the external magnetic field.

Antiviral potential of plant polysaccharide nanoparticles actuating non-specific immunity.

The development of high-end targeted drugs and vaccines against modern pandemic infections, such as COVID-19, can take a too long time that lets the epidemic spin up and harms society. However, the countermeasures must be applied against the infection in this period until the targeted drugs became available. In this regard, the non-specific, broad-spectrum anti-viral means could be considered as a compromise allowing overcoming the period of trial. One way to enhance the ability to resist the infection is to activate the nonspecific immunity using a suitable driving-up agent, such as plant polysaccharides, particularly our drug Panavir isolated from the potato shoots. Earlier, we have shown the noticeable anti-viral and anti-bacterial activity of Panavir. Here we demonstrate the pro-inflammation activity of Panavir, which four-to-eight times intensified the ATP and MIF secretion by HL-60 cells. This effect was mediated by the active phagocytosis of the Panavir particles by the cells. We hypothesized the physiological basis of the Panavir proinflammatory activity is mediated by the indol-containing compounds (auxins) present in Panavir and acting as a plant analog of serotonin.

On the orientation of the chains in the mercerized cellulose.

The cold alkaline treatment or mercerization of cellulose is widely used in industry to enrich the cellulose raw with high-molecular-weight [Formula: see text]-cellulose. Washing out of hemicelluloses by alkalies is accompanied by the rearrangement of the cellulose chains' packing, well known as a transition between cellulose I and cellulose II. Cellulose II can also be produced by the precipitation of the cellulose solutions (regeneration). The currently accepted theory implies that in cellulose II, both mercerized and regenerated, the macromolecules are arranged antiparallelly. However, forming such a structure in the course of the mercerization seems to be significantly hindered, while it seems to be quite possible in the regeneration process. In this work, we discuss the sticking points in the theory on the antiparallel structure of mercerized cellulose from a theoretical point of view summarizing all of the available experimental data in the field.

The weak magnetic field inhibits the supramolecular self-ordering of chiral molecules.

The magnetic field can affect processes in the non-magnetic systems, including the biochemical reactions in the living cells. This phenomenon becomes possible due to the fermionic nature of an electron and significant energy gain provided by the exchange interactions. Here we report the inhibition effect of the magnetic field on the processes of the chiral supramolecular, i.e., macroscopic self-ordering in the non-magnetic model system. The observed effect is in tune with the reports on the influence of the magnetic field on the adsorption of the chiral molecules, which was explained by the effect of the chirally-induced spin-selectivity and the inhibition of the chemical reactions caused by the singlet-triplet conversion. The magneto sensitivity of the process of the chiral self-ordering directly indicates its spin-polarization nature. Tacking together all of the results in the field, we can propose that the chirality-driven exchange interactions guide the selection of the chiral molecules and explain their prevalence in the living matter. It is also probable that these forces have played a critical role in the origin of life on Earth.

Antiviral activity of the high-molecular-weight plant polysaccharides (Panavir®).

This short report is dedicated to the description of the wide antiviral and antibacterial activity of the immune-modulating agent Panavir®. Panavir® is a high-molecular-weight fraction of the polysaccharides extracted from the shoots of the Solanum tuberosum. It demonstrates activity against many types of viruses, including animal coronavirus and also against bacterial infections. These properties look very promising considering the COVID-19 epidemy and allow propose that Panavir® would be effective in the therapy of the SARS-CoV-2 infection.

Zhurkov's Stress-Driven Fracture as a Driving Force of the Microcrystalline Cellulose Formation.

Microcrystalline cellulose (MCC) is a chemically pure product of cellulose mechano-chemical conversion. It is a white powder composed of the short fragments of the plant cells widely used in the modern food industry and pharmaceutics. The acid hydrolysis of the bleached lignin-free cellulose raw is the main and necessary stage of MCC production. For this reason, the acid hydrolysis is generally accepted to be the driving force of the fragmentation of the initial cellulose fibers into MCC particles. However, the low sensibility of the MCC properties to repeating the hydrolysis forces doubting this point of view. The sharp, cleave-looking edges of the MCC particles suggesting the initial cellulose fibers were fractured; hence the hydrolysis made them brittle. Zhurkov showed that mechanical stress decreases the activation energy of the polymer fracture, which correlates with the elevated enthalpy of the MCC thermal destruction compared to the initial cellulose.

Structure and properties of helical fibers spun from cellulose solutions in [Bmim]Cl.

Man-made fibers were spun from solutions of cotton and wood cellulose in ionic liquid (1-butyl-3-methyl-imidazolium chloride, [Bmim]Cl). Depending on the concentration, cellulose dissolved in [Bmim]Cl down to macromolecules or nanofibrils. The artificial fibers had a diameter of about 100 nm, were uniform, transparent, helical, and optically active. The fibers were composed of the core and shell (∼20% of the radius). The core was composed of the dense helical pseudofibrils of about 30 nm in thick occupying of about 40% of the area of the fiber core cross-section. The tensile strength of the whole fiber was, on average, 250 MPa, while that of the individual pseudofibrils was ∼1.1 GPa. The tensile-strength dependencies were two-stage with drastically different Young's modules. We explain the shape of the loading curves as well as the strength of the fibers by the friction between the twisted pseudofibrils in the core.

The fibrils untwisting limits the rate of cellulose nitration process.

The rate of cellulose nitration is lower compared to the low molecular weight substances. Theoretical estimates assess that the rate of the nitrating agents' diffusion cannot provide for the characteristic time of cellulose nitration, as the densely packed regions are too small. However, the electrostatic barrier between the nitrating mixture and the microcrystallites makes the latter inaccessible for the nitronium ion. The cellulose nitration rate decreases and the transformation of elementary fibril structure occurs at the same degree of substitution corresponding to a complete nitration of the fibrils' surface. The supercoiled macromolecules in the elementary fibrils cannot dissociate without untwisting. The fibrils' untwisting as well as their swelling are very slow. Thus, we propose that the nanofibrils' untwisting limits the rate of the nitronium ion transport into the cellulose nanofibrils and, thus, the rate of the nitration reaction as a whole.

Ultrashort ssDNA in Retinoblastoma Patients Blood Plasma Detected by a Novel High Resolution HPLC Technique: a Preliminary Report.

A significant population of ultrashort (50-150n) single-stranded DNA fragments were found in exosome-free blood plasma of retinoblastoma patients (6.84 ng mL-1), but not in plasma of healthy donors. An original high resolution HPLC technique has been proposed to reveal and characterize this peculiarity. To solve this task, a novel molecular size exclusion - anion exchange analytical technique was developed. Its applicability to diagnostics and oncogenesis research is quizzed here.

Twisting of Fibers Balancing the Gel⁻Sol Transition in Cellulose Aqueous Suspensions.

Cellulose hydrogels and films are advantageous materials that are applied in modern industry and medicine. Cellulose hydrogels have a stable scaffold and never form films upon drying, while viscous cellulose hydrosols are liquids that could be used for film production. So, stabilizing either a gel or sol state in cellulose suspensions is a worthwhile challenge, significant for the practical applications. However, there is no theory describing the cellulose fibers' behavior and processes underlying cellulose-gel-scaffold stabilizing. In this work, we provide a phenomenological mechanism explaining the transition between the stable-gel and shapeless-sol states in a cellulose suspension. We suppose that cellulose macromolecules and nanofibrils under strong dispersing treatment (such as sonication) partially untwist and dissociate, and then reassemble in a 3D scaffold having the individual elements twisted in the nodes. The latter leads to an exponential increase in friction forces between the fibers and to the corresponding fastening of the scaffold. We confirm our theory by the data on the circular dichroism of the cellulose suspensions, as well as by the direct scanning electron microscope (SEM) observations and theoretical assessments.