Search

New amiridine-thiouracil conjugates with different substituents in the pyrimidine fragment (R = CH 3 , CF 2 Н, CF 3 , (CF 2 ) 2 H) and different spacer lengths (n = 1-3) were synthesized. The conjugates rather weakly inhibit acetylcholinesterase (AChE) and exhibit high inhibitory activity (IC 50 up to 0.752 ± 0.021 µM) and selectivity to butyrylcholinesterase (BChE), which increases with spacer elongation; the lead compounds are 11c, 12c, and 13c. The conjugates are mixed-type reversible inhibitors of both cholinesterases and practically do not inhibit the structurally related off-target enzyme carboxylesterase. The results of molecular docking to AChE and BChE are consistent with the experiment on enzyme inhibition and explain the structure-activity relationships, including the rather low anti-AChE activity and the high anti-BChE activity of long-chain conjugates. The lead compounds displace propidium from the AChE peripheral anion site (PAS) at the level of the reference compound donepezil, which agrees with the mixed-type mechanism of AChE inhibition and the main mode of binding of conjugates in the active site of AChE due to the interaction of the pyrimidine moiety with the PAS. This indicates the ability of the studied conjugates to block AChE-induced aggregation of β-amyloid, thereby exerting a disease-modifying effect. According to computer calculations, all synthesized conjugates have an ADME profile acceptable for drugs., (© 2023 Deutsche Pharmazeutische Gesellschaft.)

In vitro/in vivo detection of copper ions is a challenging task but one which is important in the development of new approaches to the diagnosis and treatment of cancer and hereditary diseases such as Alzheimer's, Wilson's, etc. In this paper, we present a nanopipette sensor capable of measuring Cu 2+ ions with a linear range from 0.1 to 10 μM in vitro and in vivo. Using the gold-modified nanopipette sensor with a copper chelating ligand, we evaluated the accumulation ability of the liposomal form of an anticancer Cu-containing complex at three levels of biological organization. First, we detected Cu 2+ ions in a single cell model of human breast adenocarcinoma MCF-7 and in murine melanoma B16 cells. The insertion of the nanoelectrode did not result in leakage of the cell membrane. We then evaluated the distribution of the Cu-complex in MCF-7 tumor spheroids and found that the diffusion-limited accumulation was a function of the depth, typical for 3D culture. Finally, we demonstrated the use of the sensor for Cu 2+ ion detection in the brain of an APP/PS1 transgenic mouse model of Alzheimer's disease and tumor-bearing mice in response to injection (2 mg kg -1 ) of the liposomal form of the anticancer Cu-containing complex. Enhanced stability and selectivity, as well as distinct copper oxidation peaks, confirmed that the developed sensor is a promising tool for testing various types of biological systems. In summary, this research has demonstrated a minimally invasive electrochemical technique with high temporal resolution that can be used for the study of metabolism of copper or copper-based drugs in vitro and in vivo.

Effective therapeutics for Alzheimer's disease (AD) are in great demand worldwide. In our previous work, we responded to this need by synthesizing novel drug candidates consisting of 4-amino-2,3-polymethylenequinolines conjugated with butylated hydroxytoluene via fixed-length alkylimine or alkylamine linkers (spacers) and studying their bioactivities pertaining to AD treatment. Here, we report significant extensions of these studies, including the use of variable-length spacers and more detailed biological characterizations. Conjugates were potent inhibitors of acetylcholinesterase (AChE, the most active was 17d IC 50 15.1 ± 0.2 nM) and butyrylcholinesterase (BChE, the most active was 18d : IC 50 5.96 ± 0.58 nM), with weak inhibition of off-target carboxylesterase. Conjugates with alkylamine spacers were more effective cholinesterase inhibitors than alkylimine analogs. Optimal inhibition for AChE was exhibited by cyclohexaquinoline and for BChE by cycloheptaquinoline. Increasing spacer length elevated the potency against both cholinesterases. Structure-activity relationships agreed with docking results. Mixed-type reversible AChE inhibition, dual docking to catalytic and peripheral anionic sites, and propidium iodide displacement suggested the potential of hybrids to block AChE-induced β -amyloid (A β ) aggregation. Hybrids also exhibited the inhibition of A β self-aggregation in the thioflavin test; those with a hexaquinoline ring and C8 spacer were the most active. Conjugates demonstrated high antioxidant activity in ABTS and FRAP assays as well as the inhibition of luminol chemiluminescence and lipid peroxidation in mouse brain homogenates. Quantum-chemical calculations explained antioxidant results. Computed ADMET profiles indicated favorable blood-brain barrier permeability, suggesting the CNS activity potential. Thus, the conjugates could be considered promising multifunctional agents for the potential treatment of AD.

Mutations that disrupt the function of the DNA/RNA-binding protein FUS could cause amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. One of the key features in ALS pathogenesis is the formation of insoluble protein aggregates containing aberrant isoforms of the FUS protein in the cytoplasm of upper and lower motor neurons. Reproduction of human pathology in animal models is the main tool for studying FUS-associated pathology and searching for potential therapeutic agents for ALS treatment. In this review, we provide a systematic analysis of the role of FUS protein in ALS pathogenesis and an overview of the results of modelling FUS-proteinopathy in animals.

Background: Sesquiterpene lactones are secondary plant metabolites with a wide variety of biological activities. The process of lactone conjugation to other pharmacophores can increase the efficacy and specificity of the conjugated agent effect on molecular targets in various diseases, including brain pathologies. Derivatives of biogenic indoles, including neurotransmitter serotonin, are of considerable interest as potential pharmacophores. Most of these compounds have neurotropic activity and, therefore, can be used in the synthesis of new drugs with neuroprotective properties., Aim: The aim of this experimental synthesis was to generate potential treatment agents for Alzheimer's disease using serotonin conjugated with natural sesquiterpene lactones., Methods: Three novel compounds were obtained via the Michael reaction and used for biological testing. The obtained conjugates demonstrated complex neuroprotective activities. Serotonin conjugated to isoalantolactone exhibited strong antioxidant and mitoprotective activities., Results: The agent was also found to inhibit β-site amyloid precursor protein cleaving enzyme 1 (BACE-1), prevent the aggregation of β-amyloid peptide 1-42, and protect SH-SY5Y neuroblastoma cells from neurotoxins such as glutamate and H 2 O 2 . In a transgenic animal model of Alzheimer's disease (5xFAD line), the conjugated agent restored declined cognitive functions and improved learning and memory., Conclusion: In conclusion, the obtained results indicate that serotonin conjugates to sesquiterpene lactones are promising agents for the treatment of symptoms associated with Alzheimer's disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The modification of photocathodes based on copper(I) oxide (COPC) by coating with ZnO nanoparticles or graphene oxide (GO) with different compositions and morphologies is considered. To cover the catalyst surface with graphene oxide, a technique was proposed via freezing of a sprayed aqueous suspension of graphene oxide followed by sublimation drying under vacuum conditions. This method improves the uniformity of the GO layer in comparison with the traditional drop-casting method and, as a result, improves the photocatalytic properties of the COPC. The influence of the composition and morphology of graphene oxide on the photocatalytic activity and stability of COPC has been established. ZnO nanoparticles and GO particles in contact with copper(I) oxide increase the photocurrent density by the more efficient separation of light-generated charge carriers, providing higher photocathode stability required in photocatalytic water splitting.

The synthesis of photothermal carbon/hydroxyapatite composites poses challenges due to the binding modes and relatively low photothermal conversion efficiency. To address these challenges, the calcium ions chelated by photothermal carbon dots (PTC-CDs) served as the calcium source for the synthesis of photothermal carbon dots chelated hydroxyapatite (PTC-HA) filler via the coprecipitation method. The coordination constant K and chelation sites of PTC-HA were 7.20 × 10 2 and 1.61, respectively. Compared to PTC-CDs, the coordination constant K and chelation sites of PTC-HA decreased by 88 and 35% due to chelating to hydroxyapatite, respectively. PTC-HA possesses fluorescence and photothermal performance with a 62.4% photothermal conversion efficiency. The incorporation of PTC-HA filler significantly enhances as high as 76% the adhesion performance of the adhesive hydrogel. PTC-HA with high photothermal conversion efficiency and enhancing adhesion performance holds promise for applications in high photothermal conversion efficiency, offering tissue adhesive properties and fluorescence capabilities to the hydrogel.

In this study, the use of anionic polymerization for the synthesis of living poly(dimethylsiloxane) or PDMS-Li + , as well as poly(2-vinylpyridine) or P2VP-Li + homopolymers, and the subsequent use of chlorosilane chemistry in order for the two blocks to be covalently joined leading to PDMS- b -P2VP copolymers is proposed. High vacuum manipulations enabled the synthesis of well-defined materials with different molecular weights (Μ¯n, from 9.8 to 36.0 kg/mol) and volume fraction ratios (φ, from 0.15 to 0.67). The Μ¯n values, dispersity indices, and composition were determined through membrane/vapor pressure osmometry (MO/VPO), size exclusion chromatography (SEC), and proton nuclear magnetic resonance spectroscopy ( 1 H NMR), respectively, while the thermal transitions were determined via differential scanning calorimetry (DSC). The morphological characterization results suggested that for common composition ratios, lamellar, cylindrical, and spherical phases with domain periodicities ranging from approximately 15 to 39 nm are formed. A post-polymerization chemical modification reaction to quaternize the nitrogen atom in some of the P2VP monomeric units in the copolymer with the highest P2VP content, and the additional characterizations through 1 H NMR, infrared spectroscopy, DSC, and contact angle are reported. The synthesis, characterization, and quaternization of the copolymer structure are important findings toward the preparation of functional materials with enhanced properties suitable for various nanotechnology applications.

Biomolecular nanoreactors are constructed from chemical elements many of which have magnetic and nonmagnetic stable isotopes. The magnetic isotope effects (MIE) were discovered in experiments with the cells enriched with different isotopes of magnesium, magnetic or nonmagnetic ones. The striking catalytic effect of the magnetic isotope, 25 Mg, was revealed in the reaction of ATP hydrolysis driven by myosin, the biomolecular motor utilizing the chemical energy of ATP to perform the mechanical work. The rate of the enzymatic ATP hydrolysis with 25 Mg as the enzyme cofactor is twice higher than the rates of the reactions with nonmagnetic 24 Mg or 26 Mg. A similar effect of the nuclear spin catalysis was revealed in the experiments with zinc as the myosin cofactor. MIE unambiguously indicate that, in the chemo-mechanical process catalyzed by the molecular motor, there is a limiting step which depends on the electron spin state of the reagents, and this step is accelerated by the nuclear spin of the magnetic isotope. The recent developments in this field highlight promising venues for future research of MIE in biophysics with possible applications of the magnetic isotopes in medical physics including radiation medicine and biomedical effects of electromagnetic fields., Competing Interests: Conflict of interestThe author declares no competing interests., (© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature 2023, corrected publication 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The passage of cathodic current through the acidized aqueous bromate solution (catholyte) leads to a negative shift of the average oxidation degree of Br atoms. It means a distribution of Br-containing species in various oxidation states between -1 and +5, which are mutually transformed via numerous protonation/deprotonation, chemical, and redox/electrochemical steps. This process is also accompanied by the change in the proton (H + ) concentration, both due to the participation of H + ions in these steps and due to the H + flux through the cation-exchange membrane separating the cathodic and anodic compartments. Variations of the composition of the catholyte concentrations of all these components has been analyzed for various initial concentrations of sulfuric acid, c A (0.015-0.3 M), and two values of the total concentrations of Br atoms inside the system, c 0 (0.1 or 1.0 M of Br atoms), as functions of the average Br-atom oxidation degree, tot , under the condition of the thermodynamic equilibrium of the above transformations. It is shown that during the exhaustion of the redox capacity of the catholyte ( x pass from 5 to -1), the pH value passes through a maximum. Its height and the corresponding average oxidation state of bromine atoms depend on the initial bromate/acid ratio. The constructed algorithm can be used to select the initial acid content in the bromate catholyte, which is optimal from the point of view of preventing the formation of liquid bromine at the maximum content of electroactive compounds.x pass from 5 to -1), the pH value passes through a maximum. Its height and the corresponding average oxidation state of bromine atoms depend on the initial bromate/acid ratio. The constructed algorithm can be used to select the initial acid content in the bromate catholyte, which is optimal from the point of view of preventing the formation of liquid bromine at the maximum content of electroactive compounds.

A bis(aza-18-crown-6)-containing 2,5-di(benzylidene)cyclopentanone and a bis(ammoniopropyl) derivative of 1,2-di(4-pyridyl)ethylene in MeCN were found to form a supramolecular charge-transfer complex, which can act as an "off-on" fluorescent sensor for the Ca 2+ and 1,12-dodecanediammonium ions. The molecular structure of this complex in solution was studied by density functional theory calculations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gromov, Fomina, Zdorovenko, Fakhrutdinov and Ushakov.)

Successful clinical methods for tumor elimination include a combination of surgical resection, radiotherapy, and chemotherapy. Radiotherapy is one of the crucial components of the cancer treatment regimens which allow to extend patient life expectancy. Current cutting-edge radiotherapy research is focused on the identification of methods that should increase cancer cell sensitivity to radiation and activate anti-cancer immunity mechanisms. Radiation treatment activates various cells of the tumor microenvironment (TME) and impacts tumor growth, angiogenesis, and anti-cancer immunity. Radiotherapy was shown to regulate signaling and anti-cancer functions of various TME immune and vasculature cell components, including tumor-associated macrophages, dendritic cells, endothelial cells, cancer-associated fibroblasts (CAFs), natural killers, and other T cell subsets. Dual effects of radiation, including metastasis-promoting effects and activation of oxidative stress, have been detected, suggesting that radiotherapy triggers heterogeneous targets. In this review, we critically discuss the activation of TME and angiogenesis during radiotherapy which is used to strengthen the effects of novel immunotherapy. Intracellular, genetic, and epigenetic mechanisms of signaling and clinical manipulations of immune responses and oxidative stress by radiotherapy are accented. Current findings indicate that radiotherapy should be considered as a supporting instrument for immunotherapy to limit the cancer-promoting effects of TME. To increase cancer-free survival rates, it is recommended to combine personalized radiation therapy methods with TME-targeting drugs, including immune checkpoint inhibitors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhao, Mo, Neganova, Aleksandrova, Tse, Chubarev, Fan, Sukocheva and Liu.)

Terahertz (THz) technology offers a variety of applications in label-free medical diagnosis and therapy, majority of which rely on the effective medium theory that assumes biological tissues to be optically isotropic and homogeneous at the scale posed by the THz wavelengths. Meanwhile, most recent research discovered mesoscale ([Formula: see text]) heterogeneities of tissues; [Formula: see text] is a wavelength. This posed a problem of studying the related scattering and polarization effects of THz-wave-tissue interactions, while there is still a lack of appropriate tools and instruments for such studies. To address this challenge, in this paper, quantitative polarization-sensitive reflection-mode THz solid immersion (SI) microscope is developed, that comprises a silicon hemisphere-based SI lens, metal-wire-grid polarizer and analyzer, a continuous-wave 0.6 THz ([Formula: see text] µm) backward-wave oscillator (BWO), and a Golay detector. It makes possible the study of local polarization-dependent THz response of mesoscale tissue elements with the resolution as high as [Formula: see text]. It is applied to retrieve the refractive index distributions over the freshly-excised rat brain for the two orthogonal linear polarizations of the THz beam, aimed at uncovering the THz birefringence (structural optical anisotropy) of tissues. The most pronounced birefringence is observed for the Corpus callosum, formed by well-oriented and densely-packed axons bridging the cerebral hemispheres. The observed results are verified by the THz pulsed spectroscopy of the porcine brain, which confirms higher refractive index of the Corpus callosum when the THz beam is polarized along axons. Our findings highlight a potential of the quantitative polarization THz microscopy in biophotonics and medical imaging., (© 2023. Springer Nature Limited.)

New hybrid structures based on memantine and edaravone molecules, in which the pyrazolone ring and adamantane fragments are linked by an alkyl linker, were synthesized. It was found that, in addition to the ability to block the intrachannel site of NMDA receptors, the new hybrid compounds exhibit the property of blockers of the allosteric site of NMDA receptors, which is not inherent in memantine and edaravone preparations. The most active hit compound was determined, which, along with the properties of a two-site blocker of the NMDA receptor, exhibits a pronounced activity as an inhibitor of lipid peroxidation, similarly to the drug edaravone., (© 2023. Pleiades Publishing, Ltd.)

The accuracy of the ion flight time measurement in the time-of-flight mass spectrometer is critical to achieving high resolution. The pulse amplitude variation of the detector pulses leads to the registration time spread at a given pulse detection threshold. This time spread can be eliminated by determining the position of the pulse apex. To determine the position of the pulse apex, the output of the ion detector is fed simultaneously to the two channels of the time-to-digital converter. In this case, the first channel is set to register the leading edge, and the second channel is set to register the trailing edge of the pulse. Using a simple processing of the received data, the position of the pulse tip is determined. Thus, the dependence of the temporal position of the peak on the pulse amplitude is largely eliminated. Examples are given, and the efficiency of using this algorithm to increase the resolution of time-of-flight mass spectral peak registration is demonstrated., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Chromosomes are exceedingly long topologically-constrained polymers compacted in a cell nucleus. We recently suggested that chromosomes are organized into loops by an active process of loop extrusion. Yet loops remain elusive to direct observations in living cells; detection and characterization of myriads of such loops is a major challenge. The lack of a tractable physical model of a polymer folded into loops limits our ability to interpret experimental data and detect loops. Here, we introduce a new physical model - a polymer folded into a sequence of loops, and solve it analytically. Our model and a simple geometrical argument show how loops affect statistics of contacts in a polymer across different scales, explaining universally observed shapes of the contact probability. Moreover, we reveal that folding into loops reduces the density of topological entanglements, a novel phenomenon we refer as "the dilution of entanglements". Supported by simulations this finding suggests that up to ~ 1 - 2Mb chromosomes with loops are not topologically constrained, yet become crumpled at larger scales. Our theoretical framework allows inference of loop characteristics, draws a new picture of chromosome organization, and shows how folding into loops affects topological properties of crumpled polymers.

The self-discharge of an electric double-layer capacitor with composite activated carbon electrodes and aqueous electrolyte (1 M MgSO 4 ) was studied in detail. Under a long-term potentiostatic charge (stabilization), a decrease in the discharge capacity was observed in the region of voltages exceeding 0.8 V. The self-discharge process consists of two phases. In the initial phase, the cell voltage drop is due to the charge redistribution inside electrodes. During the main phase, the charge transfer between the electrodes determines the voltage drop. The optimal stabilization time of the self-discharge was found to be 50 min at 1.4 V. Hydrophilization of the negative electrode occurred during long-term polarization due to the formation of epoxy functional groups.

The ubiquitin-proteasome system (UPS) provides hydrolysis of most intracellular proteins in proteasomes. There are various forms of proteasomes that differ, among other things, in the set of proteolytic subunits and the presence of activators. Alzheimer's disease (AD) is characterized by disturbances in the functional state of the UPS. At the same time, an increase in the expression of certain forms of proteasomes, in particular, proteasomes containing immune subunits (nonconstitutive proteasomes), has been shown. Here, we studied dynamic changes in the expression of catalytic proteasome subunit genes and corresponding proteins in the cerebral cortex of animals using a mouse model of AD (5xFAD transgenic mice). Increases by 4 and 6 folds in transcripts of the PSMB9 and PSMB8 genes encoding immune proteasome subunits were detected, as well as a significant increase in the content of immune β-subunits (by 2.8 folds, β1i; 2.2 folds, β2i) in samples from 5xFAD mice at the age of 380 days, compared with samples from mice at 60 days of age. Moreover, the activation of both 20S and 26S proteasomes containing immune subunits were revealed in samples from 380 days old 5xFAD mice by electrophoresis in native conditions. This indicates activated synthesis of the immune subunits and assembly of nonconstitutive proteasomes at the terminal stage of pathology development. The obtained data, in combination with the available literature, indicate that the activation of nonconstitutive proteasomes is a universal phenomenon characteristic of various animal models of AD, which may reflect both the development of neuroinflammation and adaptive processes in tissues induced by the accumulation of toxic protein aggegates.

Proteasomes are key components of the ubiquitin-proteasome system. Various forms of proteasomes are known. During aging, disturbances in the functioning of proteasomes have been revealed, as well as increased expression of their particular forms. Considering these data, we studied the expression of genes encoding the constitutive and immune subunits of proteasomes in cerebral cortex samples from C57BL/6 mice at the ages of 60, 190, 380, and 720 days. In addition, the contents of constitutive and immune proteasome subunits, chymotrypsin-like and caspase-like activities of proteasome pools, as well as the activity of the β5i immune subunit were studied in tissue homogenates. The chymotrypsin-like activity and the activity of the β5i subunit of different forms of proteasomes separated by electrophoresis in native gel were characterized. Compared with samples from young animals, in the cerebral cortex of animals at an age of 720 days the following changes in the expression patterns of proteasome genes were revealed: a decreased expression of the PSMB5 gene encoding constitutive proteasome subunit β5; increased expression of genes encoding immune proteasome subunits β5i and β1i. In tissue homogenates of aged mice, an increase in the content of immune subunits β1i and β2i was shown. In samples from old animals, chymotrypsin-like activity was decreased and a tendency to a decrease in caspase-like activity of proteasomes as well as the β5i subunit activity was revealed. Analysis of the activity of native complexes in tissues obtained from old animals revealed decreased chymotrypsin-like activity of 26S and 20S proteasomes containing the β5i subunit. Based on the obtained data, it can be assumed that changes in the pool of nonconstitutive proteasomes reflect aging-associated adaptive processes in the mouse brain.

Entomopathogenic bacteria of the genus Photorhabdus secrete protease S (PrtS), which is considered a virulence factor. We found that in the Photorhabdus genomes, immediately after the prtS genes, there are genes that encode small hypothetical proteins homologous to emfourin, a recently discovered protein inhibitor of metalloproteases. The gene of emfourin-like inhibitor from Photorhabdus laumondii subsp. laumondii TT01 was cloned and expressed in Escherichia coli cells. The recombinant protein, named photorin (Phin), was purified by metal-chelate affinity and gel permeation chromatography and characterized. It has been established that Phin is a monomer and inhibits activity of protealysin and thermolysin, which, similar to PrtS, belong to the M4 peptidase family. Inhibition constants were 1.0 ± 0.3 and 10 ± 2 µM, respectively. It was also demonstrated that Phin is able to suppress proteolytic activity of P. laumondii culture fluid (half-maximal inhibition concentration 3.9 ± 0.3 nM). Polyclonal antibodies to Phin were obtained, and it was shown by immunoblotting that P. laumondii cells produce Phin. Thus, the prtS genes in entomopathogenic bacteria of the genus Photorhabdus are colocalized with the genes of emfourin-like inhibitors, which probably regulate activity of the enzyme during infection. Strict regulation of the activity of proteolytic enzymes is essential for functioning of all living systems. At the same time, the principles of regulation of protease activity by protein inhibitors remain poorly understood. Bacterial protease-inhibitor pairs, such as the PrtS and Phin pair, are promising models for in vivo studies of these principles. Bacteria of the genus Photorhabdus have a complex life cycle with multiple hosts, being both nematode symbionts and powerful insect pathogens. This provides a unique opportunity to use the PrtS and Phin pair as a model for studying the principles of protease activity regulation by proteinaceous inhibitors in the context of bacterial interactions with different types of hosts.

Quantum Otto and Carnot engines have recently been receiving attention due to their ability to achieve high efficiencies and powers based on the laws of quantum mechanics. This paper discusses the theory, progress, and possible applications of quantum Otto and Carnot engines, such as energy production, cooling, and nanoscale technologies. In particular, we investigate a two-spin Heisenberg system that works as a substance in quantum Otto and Carnot cycles while exposed to an external magnetic field with both Dzyaloshinsky-Moriya and dipole-dipole interactions. The four stages of engine cycles are subject to analysis with respect to the heat exchanges that occur between the hot and cold reservoirs, alongside the work done during each stage. The operating conditions of the heat engine, refrigerator, thermal accelerator, and heater are all achieved. Moreover, our results demonstrate that the laws of thermodynamics are strictly upheld and the Carnot cycle produces more useful work than that of the Otto cycle.

The bone-targeting mechanism of clinic bisphosphonate-type drugs, such as alendronate, risedronate, and ibandronate, relies on chelated calcium ions on the surface of the bone mineralized matrix for the treatment of osteoporosis. EGTA with aminocarboxyl chelating ligands can specifically chelate calcium ions. Inspired by the bone-targeting mechanism of bisphosphonates, we hypothesize that EGTA-derived carbon dots (EGTA-CDs) hold bone-targeting ability. For the target-oriented synthesis of EGTA-CDs and to endow CDs with bone targeting, we designed calcium ion chelating agents as precursors, including aminocarboxyl chelating agents (EGTA and EDTA) and bisphosphonate agents (ALN and HEDP) for the target-oriented synthesis of aminocarboxyl-derived CDs (EGTA-CDs and EDTA-CDs) and bisphosphonate-derived CDs (ALN-CDs and HEDP-CDs) with high synthetic yield. The synthetic yield of EGTA-CDs reached 87.6%. Aminocarboxyl-derived CDs and bisphosphonate-derived CDs retain the chelation ability of calcium ions and can specifically bind calcium ions. The chemical environment bone-targeting value coordination constant K and chelation sites of EGTA-CDs were 6.48 × 10 4 M -1 and 4.12, respectively. A novel method was established to demonstrate the bone-targeting capability of chelate-functionalized carbon dots using fluorescence quenching in a simulated bone trauma microenvironment. EGTA-CDs exhibit superior bone-targeting ability compared with other aminocarboxyl-derived CDs and bisphosphonate-derived CDs. EGTA-CDs display exceptional specificity toward calcium ions and better bone affinity than ALN-CDs, suggesting their potential as novel bone-targeting drugs. EGTA-CDs with strong calcium ion chelating ability have calcium ion affinity in simulated body fluid and bone-targeting ability in a simulated bone trauma microenvironment. These findings offer new avenues for the development of advanced bone-targeting strategies.

We investigated the inhibitory activities of novel 9-phosphoryl-9,10-dihydroacridines and 9-phosphorylacridines against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and carboxylesterase (CES). We also studied the abilities of the new compounds to interfere with the self-aggregation of β-amyloid (Aβ 42 ) in the thioflavin test as well as their antioxidant activities in the ABTS and FRAP assays. We used molecular docking, molecular dynamics simulations, and quantum-chemical calculations to explain experimental results. All new compounds weakly inhibited AChE and off-target CES. Dihydroacridines with aryl substituents in the phosphoryl moiety inhibited BChE; the most active were the dibenzyloxy derivative 1d and its diphenethyl bioisostere 1e (IC 50 = 2.90 ± 0.23 µM and 3.22 ± 0.25 µM, respectively). Only one acridine, 2d , an analog of dihydroacridine, 1d , was an effective BChE inhibitor (IC 50 = 6.90 ± 0.55 μM), consistent with docking results. Dihydroacridines inhibited Aβ 42 self-aggregation; 1d and 1e were the most active (58.9% ± 4.7% and 46.9% ± 4.2%, respectively). All dihydroacridines 1 demonstrated high ABTS •+ -scavenging and iron-reducing activities comparable to Trolox, but acridines 2 were almost inactive. Observed features were well explained by quantum-chemical calculations. ADMET parameters calculated for all compounds predicted favorable intestinal absorption, good blood-brain barrier permeability, and low cardiac toxicity. Overall, the best results were obtained for two dihydroacridine derivatives 1d and 1e with dibenzyloxy and diphenethyl substituents in the phosphoryl moiety. These compounds displayed high inhibition of BChE activity and Aβ 42 self-aggregation, high antioxidant activity, and favorable predicted ADMET profiles. Therefore, we consider 1d and 1e as lead compounds for further in-depth studies as potential anti-AD preparations., Competing Interests: RR currently serves as a member of the advisory board of NeuroX1, a startup biotechnology company that is developing a software platform for the discovery and development of drugs for neurodegenerative diseases. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Makhaeva, Kovaleva, Rudakova, Boltneva, Lushchekina, Astakhova, Timokhina, Serebryakova, Shchepochkin, Averkov, Utepova, Demina, Radchenko, Palyulin, Fisenko, Bachurin, Chupakhin, Charushin and Richardson.)

VO and VO 2 vanadyl groups with short (typically 1.57-1.68 Å), essentially covalent, V-O bonds are common for V 4+ -bearing oxysalts with [5]- and [6]-coordinated vanadium. There is a clear negative correlation between vanadyl bond lengths and wavenumbers of the bands of V-O stretching vibrations in infrared spectra (in the range 1000-880 cm -1 ). Optical, structural and chemical data for vanadyl minerals are used to calculate Gladstone-Dale compatibility coefficients. Gladstone-Dale compatibility indices of minerals containing vanadyl bonds are compared with total electronic polarizabilities of V 4+ . Unlike compounds of [5]-coordinated Ti 4+ , for most minerals with V 4+ =O (vanadyl) bonds there is good agreement between measured refractive indices and those calculated based on the polarizability concept.

The crystal chemistry of the natural microporous two-layer aluminosilicates (2D zeolites) latiumite and tuscanite is re-investigated based on new data on the chemical composition, crystal structures, and infrared and Raman spectra. The CO 3 2- -depleted and P- and H-enriched samples from Sacrofano paleovolcano, Lazio, Italy, are studied. Both minerals are monoclinic; latiumite P2 1 , a = 12.0206 (3), b = 5.09502 (10), c = 10.8527 (3) Å, β = 107.010 (3)°, V = 635.60 (3) Å 3 and tuscanite P2 1 /a, a = 23.9846 (9), b = 5.09694 (15), c = 10.8504 (4) Å, β = 107.032 (4)°, V = 1268.26 (8) Å 3 . The obtained crystal chemical formulae (Z = 2 for both minerals) are [(H 3 O) 0.48 (H 2 O) 0.24 K 0.28 ](Ca 2.48 K 0.21 Na 0.21 Sr 0.06 Mg 0.04 )(Si 2.86 Al 2.14 O 11 )[(SO 4 ) 0.70 (PO 4 ) 0.20 ](CO 3 ) 0.10 for latiumite and [(H 3 O) 0.96 (H 2 O) 0.58 K 0.46 ](Ca 4.94 K 0.44 Na 0.45 Sr 0.09 Mg 0.08 )(Si 5.80 Al 4.20 O 22 )[(SO 4 ) 1.53 (PO 4 ) 0.33 ](CO 3 ) 0.14 anion. Hydrolytic alteration of these minerals results in partial leaching of potassium accompanied by protonation and hydration which is an important precondition for the existence of ion/proton conductivity of related materials.4 3- anion. Hydrolytic alteration of these minerals results in partial leaching of potassium accompanied by protonation and hydration which is an important precondition for the existence of ion/proton conductivity of related materials.

The HDAC6 (histone deacetylase 6) enzyme plays a key role in many biological processes, including cell division, apoptosis, and immune response. To date, HDAC6 inhibitors are being developed as effective drugs for the treatment of various diseases. In this work, adequate QSAR models of HDAC6 inhibitors are proposed. They are integrated into the developed application HDAC6 Detector, which is freely available at https://ovttiras-hdac6-detector-hdac6-detector-app-yzh8y5.streamlit.app/. The web application HDAC6 Detector can be used to perform virtual screening of HDAC6 inhibitors by dividing the compounds into active and inactive ones relative to the reference vorinostat compound (IC 50  = 10.4 nM). The web application implements a structural interpretation of the developed QSAR models. In addition, the application can evaluate the compliance of a compound with Lipinski's rule. The developed models are used for virtual screening of a series of 12 new hydroxamic acids, namely, the derivatives of 3-hydroxyquinazoline-4(3 H )-ones and 2-aryl-2,3-dihydroquinazoline-4(1 H )-ones. In vitro evaluation of the inhibitory activity of this series of compounds against HDAC6 allowed us to confirm the results of virtual screening and to select promising compounds V-6 and V-11, the IC 50 of which is 0.99 and 0.81 nM, respectively.

Dysfunction of the RNA-binding protein (RBP) FUS implicated in RNA metabolism can cause amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. Mutations affecting FUS nuclear localization can drive RNA splicing defects and stimulate the formation of non-amyloid inclusions in affected neurons. However, the mechanism by which FUS mutations contribute to the development of ALS remains uncertain. Here we describe a pattern of RNA splicing changes in the dynamics of the continuous proteinopathy induced by mislocalized FUS. We show that the decrease in intron retention of FUS-associated transcripts represents the hallmark of the pathogenesis of ALS and is the earliest molecular event in the course of progression of the disease. As FUS aggregation increases, the pattern of RNA splicing changes, becoming more complex, including a decrease in the inclusion of neuron-specific microexons and induction of cryptic exon splicing due to the sequestration of additional RBPs into FUS aggregates. Crucially, the identified features of the pathological splicing pattern are also observed in ALS patients in both sporadic and familial cases. Our data provide evidence that both a loss of nuclear FUS function due to mislocalization and the subsequent cytoplasmic aggregation of mutant protein lead to the disruption of RNA splicing in a multistep fashion during FUS aggregation., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

This study comprehensively investigates the efficiency of the formulation of tetraethoxysilane (TEOS) and 3-aminopropyltriethoxysilane (APTES) copolymer in sol-gel syntheses as part of a multivariate experiment. A methodology-based response surface was used to estimate the influence of independent variables such as polymerization time and temperature, as well as the ratio of TEOS and APTES components on the surface charge response function and product yield, and in order to predict the best response values. Analysis of variance showed that when assessing the value of the zeta potential, the polymerization temperature and the ratio of components are statistically significant factors, but on the other hand, when assessing the yield of the finished product, only the ratio of components is significant. The combination of various options for temperature, time and ratio of components allows one to obtain a zeta potential in the range from +61.2 mV to -48.8 mV and a product yield of up to 4.7 g. Evaluation of the data with TGA-DTA, FTIR-ATR, and ELS methods showed an unexpected result, according to which the highest degree of polymerization and the highest surface charge were inherent in an amino-deficient system. Thus, the smaller the amino component in the system (the APTES-TEOS molar ratio is 0.25), the more efficient the polycondensation is over the absorption area of the Si-O-Si band, and the higher the zeta potential.

Graphene shows strong promise for the detection of terahertz (THz) radiation due to its high carrier mobility, compatibility with on-chip waveguides and transistors, and small heat capacitance. At the same time, weak reaction of graphene's physical properties on the detected radiation can be traced down to the absence of a band gap. Here, we study the effect of electrically induced band gap on THz detection in graphene bilayer with split-gate p-n junction. We show that gap induction leads to a simultaneous increase in current and voltage responsivities. At operating temperatures of ∼25 K, the responsivity at a 20 meV band gap is from 3 to 20 times larger than that in the gapless state. The maximum voltage responsivity of our devices at 0.13 THz illumination exceeds 50 kV/W, while the noise equivalent power falls down to 36 fW/Hz 1/2 .

We studied the possibility of inhibition of histone deacetylases (HDAC) in the nuclear extract of HeLa cells by N1-hydroxy-N4-(pyridin-4-yl)succinamide (compound 1). Compound 1 inhibits HDAC and showed low toxicity for A-172, HepG2, HeLa, MCF-7, and Vero cells. HeLa cells were most sensitive to the compound. Increasing the interval between administration of compound 1 and the chemotherapeutic agent to 8 h led to an increase in the cytotoxic effect of cisplatin (actinomycin D) on HeLa cells. The combination of compound 1 with cisplatin (actinomycin D) reduced the cytotoxic effect of these drugs for non-tumor Vero cells., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

The work is dedicated to further development of our described method for analyzing mass spectra of biomolecules acquired as a result of hydrogen-deuterium exchange reactions (HDXs). The modified method consists of separating HDX distributions via their approximations by a minimum number of components corresponding to independent H/D substitutions and independent charge carrier retentions in different spatial isoforms or conformations of biomolecules with unknown primary structures. In this case, neither the natural isotopic distribution nor the exact number of active sites involved in HDXs and H + or D + attachments can be determined in advance. Original H/D electrospray mass spectra of an apamin solution were taken from our previous work. In that work, taking into account the natural isotopic distribution of apamin molecules, three main conformations of apamin ions were found as a result of separating the H/D mass spectra of the apamin solution for the gas flow with the addition of about 10% ND 3 molecules. Using the proposed modified method that does not require knowledge of the primary structure of the biomolecules gave similar results with slight deviations of calculated HDX distributions of the apamin ions from those obtained earlier. The maximum difference between mean values of the calculated HDX distributions for ions of the same charge in both cases does not exceed a few percent. In addition, HDX mass spectra of the apamin complex with an adduct of unknown structure were processed. Such analysis gave also three main fractions of ions with relatively large contributions when ND 3 was injected into a radio-frequency quadrupole. In the absence of ND 3 flow, the results of calculations for apamin and its complex were close to each other too. The formation of the apamin complex most probably in solution was confirmed by performed calculations., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

Multiple quantum (MQ) dynamics was investigated in quasi-one-dimensional 1 H zigzag spin chains in hambergite (Be 2 BO 3 OH) single crystals. Due to the non-linear arrangement of the spins, dipolar coupling strengths alternate along the chain. To solve the problem of MQ NMR experiments taking too much time due to extremely long 1 H spin-lattice relaxation times, the samples were exposed to gamma irradiation to produce the defects accelerating the relaxation. The influence of the radiation dose was investigated. The experimental dependencies of MQ coherence intensities on the MQ excitation time in alternating spin chains were obtained and compared with the theory for inhomogeneous spin chains with nearest neighbor interactions developed earlier. The correspondence of the observed MQ dynamics to the alternating spin chain was demonstrated., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A new mechanically stimulated solid-state reaction of PtCl 4 with sodium β-diketonates has been discovered. Platinum (II) β-diketonates were obtained by grinding excess sodium trifluoroacetylacetonate Na(tfac) or hexafluoroacetylacetonate Na(hfac) in a vibration ball mill, followed by subsequent heating of the resulting mixture. The reactions occur under much milder conditions (at about 170 °C) compared to similar reactions of PtCl 2 or K 2 PtCl 6 (at about 240 °C). Excess diketonate salt plays the role of a reducing agent in the conversion of Pt (IV) salt to Pt (II) compounds. The effect of grinding on properties of the ground mixtures was studied by XRD, IR, and thermal analysis methods. The difference in the course of the interaction of PtCl 4 with Na(hfac) or Na(tfac) indicates the dependence of the reaction on the ligand properties. The probable reaction mechanisms were discussed. This method of synthesis of platinum (II) β-diketonates makes it possible to substantially reduce the variety of reagents used, the number of reaction steps, the reaction time, the use of solvents, and waste generation compared to conventional solution-based methods.

Potentially toxic elements (PTEs) in urban dust of Moscow megacity and related risks have been studied. 78 samples were collected in the Moscow downtown in sites with different anthropogenic load, namely, major highways, residential area, and recreation zones. The concentrations of PTEs in urban dust were determined by ICP-MS and ICP-AES. Then, environmental, ecological and health risks of PTEs in urban dust were assessed. In addition, potential sources of PTEs in dust were identified. It is shown that Moscow dust is mainly contaminated by Sb, Zn, Pb, Cd, Cu, Sn, and Mo, which according to the data of principal component and correlation analyses can be attributed to anthropogenic sources (non-exhaust vehicle emissions). Potential ecological risk factor demonstrates that Cu, Mo, and Cd have moderate potential ecological risks in 13% of studied area, while Sb has this risk in 62% of area. Potential ecological risk indices indicate that 41% of studied territory is of moderate ecological risk. Concerning the human risks through ingestion, dermal contact, and inhalation pathways, PTEs in Moscow dust have no significant non-carcinogenic risks for adults. However, the value of total hazard index for children is 1.8 showing that non-carcinogenic risks may occur. Moreover, possible carcinogenic risks caused by Cr are evaluated. The finding of the present study can be used for ecological management in the megacity to reduce both ecological and human risks. A special attention should be given to periods of hot and dry weather and to traffic-related emissions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Spontaneous crystals of krieselite (Ge analogue of topaz) with the chemical formula Al 2 [(Ge 0.75 Si 0.25 )O 4 ](F 1.63 OH 0.37 ) were synthesized using a thermo-gradient hydrothermal method at a temperature of 600/650 °C and pressure of 100 MPa. The unit cell parameters are: a = 8.9732(8) Å, b = 8.4823(7) Å, c = 4.7379(5) Å, V = 360.62(6) Å 3 , space group Pnma. The F - /OH - content of the samples was refined by FTIR spectroscopy method. Raman spectroscopy showed the main differences between the spectra of krieselite and topaz at the ambient conditions. The assignment of observed and calculated A g bands (cm -1 ) for non-polarized Raman spectra was carried out. Using in situ Raman spectroscopy at high pressures, the dependence of the shift in the position of the main bands of the krieselite Raman spectrum on the pressure was established, and the corresponding paths of pressure induced distortion of crystal structure was assumed. According to the data of Raman spectroscopy, it was revealed that krieselite does not undergo the phase transitions up to 30 GPa. The probable way of crystal structure distortion within the space group Pnma was proposed based on simulation of high-pressure Raman spectra., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This article describes a sapphire cryoprobe as a promising solution to the significant problem of modern cryosurgery that is the monitoring of tissue freezing. This probe consists of a sapphire rod manufactured by the edge-defined film-fed growth technique from Al 2 O 3 melt and optical fibers accommodated inside the rod and connected to the source and the detector. The probe's design enables detection of spatially resolved diffuse reflected intensities of tissue optical response, which are used for the estimation of tissue freezing depth. The current type of the 12.5-mm diameter sapphire probe cooled down by the liquid nitrogen assumes a superficial cryoablation. The experimental test made by using a gelatin-intralipid tissue phantom shows the feasibility of such concept, revealing the capabilities of monitoring the freezing depth up to 10 mm by the particular instrumentation realization of the probe. This justifies a potential of sapphire-based instruments aided by optical diagnosis in modern cryosurgery., (© 2022 Wiley-VCH GmbH.)

Nitric oxide (NO) is a gaseous molecule which plays a key role in wound healing. Previously, we identified the optimal conditions for wound healing strategies using NO donors and an air plasma generator. The aim of this study was to compare the wound healing effects of binuclear dinitrosyl iron complexes with glutathione (B-DNIC-GSH) and NO-containing gas flow (NO-CGF) at their optimal NO doses (0.04 mmol for B-DNIC-GSH and 1.0 mmol for NO-CGF per 1 cm 2 ) in a rat full-thickness wound model over a 3-week period. Excised wound tissues were studied by light and transmission electron microscopy and immunohistochemical, morphometrical and statistical methods. Both treatments had an identical stimulating impact on wound healing, which indicated a higher dosage effectiveness of B-DNIC-GSH compared to the NO-CGF. B-DNIC-GSH spray application reduced inflammation and promoted fibroblast proliferation, angiogenesis and the growth of granulation tissue during the first 4 days after injury. However, prolonged NO spray effects were mild compared to NO-CGF. Future studies should determine the optimal B-DNIC-GSH solution course for a more effective wound healing stimulation.

We report the synthesis of three (3) linear triblock terpolymers, two (2) of the ABC type and one (1) of the BAC type, where A, B and C correspond to three chemically incompatible blocks such as polystyrene (PS), poly(butadiene) of exclusively (~100% vinyl-type) -1,2 microstructure (PB 1,2 ) and poly(dimethylsiloxane) (PDMS) respectively. Living anionic polymerization enabled the synthesis of narrowly dispersed terpolymers with low average molecular weights and different composition ratios, as verified by multiple molecular characterization techniques. To evaluate their self-assembly behavior, transmission electron microscopy and small-angle X-ray scattering experiments were conducted, indicating the effect of asymmetric compositions and interactions as well as inversed segment sequence on the adopted morphologies. Furthermore, post-polymerization chemical modification reactions such as hydroboration and oxidation were carried out on the extremely low molecular weight PB 1,2 in all three terpolymer samples. To justify the successful incorporation of -OH groups in the polydiene segments and the preparation of polymeric brushes, various molecular, thermal, and surface analysis measurements were carried out. The synthesis and chemical modification reactions on such triblock terpolymers are performed for the first time to the best of our knowledge and constitute a promising route to design polymers for nanotechnology applications.

The iron(III) anionic complex based on a pyruvic acid thiosemicarbazone ligand with the lithium cation Li[Fe III (thpy) 2 ]·3H 2 O (1) has been synthesized and characterized by FTIR spectroscopy, powder and single crystal X-ray diffraction, direct current magnetic susceptibility measurements, and 57 Fe Mössbauer spectroscopy. Moreover, the molecular structure of the [Fe(thpy) 2 ] - anion has been determined for the first time. The [Fe(thpy) 2 ] - units in the triclinic P 1̄ lattice of 1 are assembled into layers parallel to the bc plane. The Li + cations and water molecules are located between the layers and the structure is stabilized by hydrogen bonding. The [Fe(thpy) 2 ] - anions form interconnected dimer pairs through hydrogen bonds and short contacts with Fe⋯Fe separation of 6.7861(4) Å. According to dc magnetic measurements, compound 1 demonstrates an incipient spin-crossover transition from the LS ( S = 1/2) to the HS ( S = 5/2) state above 250 K. The Bleaney-Bowers equation for a model of an isolated LS dimer with a mean-field correction was applied to fit the experimental data of magnetic susceptibility dependence on temperature in the temperature range of 2-250 K. The intra-dimer J 1 = -0.24(3) K antiferromagnetic coupling constants were defined. The analysis of the J Fe Mössbauer spectra at 80 K and 296 K confirms the presence of the shortened distances between the iron nuclei. Moreover, the influence of the lithium cation on the stabilization of the LS state was shown for the [Fe(thpy) 2 = -0.24(3) K antiferromagnetic coupling constants were defined. The analysis of the 57 anion. BS-DFT calculations for the optimized structure of two isolated [Fe(thpy) 2 ] - anion. BS-DFT calculations for the optimized structure of two isolated [Fe(thpy) 2 (calc) = -0.92 K. DFT calculations revealed the OPBE (GGA-type) functional that correctly predicts the spin-crossover transition for the iron(III) thpy compounds. Besides, the effect of the N - anions also correctly predict a weak exchange J 1 (calc) = -0.92 K. DFT calculations revealed the OPBE (GGA-type) functional that correctly predicts the spin-crossover transition for the iron(III) thpy compounds. Besides, the effect of the N 2 O 4 , N 2 S 2 O 2 coordination environments on the energy stabilization of the LS state of iron(III) anionic thpy complexes was noted as well.2 Se 2 O 2 coordination environments on the energy stabilization of the LS state of iron(III) anionic thpy complexes was noted as well.

Conventional artificial intelligence (AI) machine vision technology, based on the von Neumann architecture, uses separate sensing, computing, and storage units to process huge amounts of vision data generated in sensory terminals. The frequent movement of redundant data between sensors, processors and memory, however, results in high-power consumption and latency. A more efficient approach is to offload some of the memory and computational tasks to sensor elements that can perceive and process the optical signal simultaneously. Here, we proposed a non-volatile photomemristor, in which the reconfigurable responsivity can be modulated by the charge and/or photon flux through it and further stored in the device. The non-volatile photomemristor has a simple two-terminal architecture, in which photoexcited carriers and oxygen-related ions are coupled, leading to a displaced and pinched hysteresis in the current-voltage characteristics. For the first time, non-volatile photomemristors implement computationally complete logic with photoresponse-stateful operations, for which the same photomemristor serves as both a logic gate and memory, using photoresponse as a physical state variable instead of light, voltage and memresistance. The polarity reversal of photomemristors shows great potential for in-memory sensing and computing with feature extraction and image recognition for neuromorphic vision., (© 2023. The Author(s).)

The laser formation of positive and negative ions on a nanostructured metal surface is observed at laser fluence below the plasma formation threshold. The laser radiation energy dependences of the yield of positive and negative Au ions and charged clusters as well as electrons from the laser-induced nanostructures on the surface of gold are obtained at laser fluence below the plasma formation threshold using a pulsed laser with a wavelength of 355 nm and a pulse duration of 0.37 ns. It is shown that the ratio of the signals of positive and negative ions is constant over the entire range of the laser radiation energies, while the ion signal dependence on the laser radiation energy is described by a power function with an exponent of 9. The role of gold nanoparticles with a size of less than 5 nm in the formation of Au ions and charged Au clusters is discussed.

A comparative analysis of specific immunobiochemical parameters, including natural antibodies (NAb) to endogenous regulators of the cardiovascular system, adrenal and gastrointestinal hormones, was performed in students aged 18-22 years with normal and increased body weight (the body mass index from 18.5 to 24.9 kg/m 2 and from 25 to 29.9 kg/m 2 , respectively). The serum content of NAb and hormones was determined by ELISA. The level of the studied indicators depended on the body mass index value. In overweight subjects, the main immune indicators of the biogenic amine system, renin-angiotensin system, and kinin system exceeded the normal. The cortisol level was higher than in subjects with normal body weight. Aldosterone secretion was less dependent on the ACTH content and was lower than in students with normal body weight. The content of cholecystokinin and gastrin corresponded to the values for overweight. These trends in hormone contents are a predisposing factor for further weight gain. Practical significance of the combined assessment of disturbances in the immunological and biochemical homeostasis has been established. Analysis of the adrenal and gastrointestinal hormones can predict the risk of weight gain, but at the same time, changes in the level of immunological indicators in subjects with increased body weight characterizes the possibility of developing cardiovascular pathologies., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

A series of previously synthesized conjugates of tacrine and salicylamide was extended by varying the structure of the salicylamide fragment and using salicylic aldehyde to synthesize salicylimine derivatives. The hybrids exhibited broad-spectrum biological activity. All new conjugates were potent inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with selectivity toward BChE. The structure of the salicylamide moiety exerted little effect on anticholinesterase activity, but AChE inhibition increased with spacer elongation. The most active conjugates were salicylimine derivatives: IC 50 values of the lead compound 10c were 0.0826 µM (AChE) and 0.0156 µM (BChE), with weak inhibition of the off-target carboxylesterase. The hybrids were mixed-type reversible inhibitors of both cholinesterases and displayed dual binding to the catalytic and peripheral anionic sites of AChE in molecular docking, which, along with experimental results on propidium iodide displacement, suggested their potential to block AChE-induced β -amyloid aggregation. All conjugates inhibited Aβ 42 self-aggregation in the thioflavin test, and inhibition increased with spacer elongation. Salicylimine 10c and salicylamide 5c with (CH 2 ) 8 spacers were the lead compounds for inhibiting Aβ 42 self-aggregation, which was corroborated by molecular docking to Aβ 42 . ABTS •+ -scavenging activity was highest for salicylamides 5a-c , intermediate for salicylimines 10a-c , low for F-containing salicylamides 7 , and non-existent for methoxybenzoylamides 6 and difluoromethoxybenzoylamides 8 . In the FRAP antioxidant (AO) assay, the test compounds displayed little or no activity. Quantum chemical analysis and molecular dynamics (MD) simulations with QM/MM potentials explained the AO structure-activity relationships. All conjugates were effective chelators of Cu 2+ , Fe 2+ , and Zn 2+ , with molar compound/metal (Cu 2+ ) ratios of 2:1 ( 5b ) and ~1:1 ( 10b ). Conjugates exerted comparable or lower cytotoxicity than tacrine on mouse hepatocytes and had favorable predicted intestinal absorption and blood-brain barrier permeability. The overall results indicate that the synthesized conjugates are promising new multifunctional agents for the potential treatment of AD.

Results from studying the effect of an applied electric voltage on the Raman spectrum of graphene deposited on a lithium niobate crystal substrate with a ferroelectric domain structure are presented. The use of the principal component method for data processing in combination with correlation analysis made it possible to reveal the contribution to the change in the spectra associated with the linear deformation of the substrate due to the inverse piezoelectric effect. An effect of the graphene coating peeling was found. Furthermore, bending deformations of the graphene coating associated with the presence of a relief on the substrate were found. An analysis of the change in the spectra of graphene under the application of an electric voltage made it possible to determine the height of this relief.

Alzheimer's disease (AD) is the most common proteinopathy, which is accompanied by a steady decrease in the patient's cognitive functions with a simultaneous accumulation of amyloid plaques in brain tissues. Amyloid plaques are extracellular aggregates of amyloid β (Aβ) and are associated with neuroinflammation and neurodegeneration. Unlike humans and all other mammals, rats and mice do not reproduce AD-like pathology because there are three amino acid substitutions in their Aβ. Amyloid plaques form in the brains of transgenic mice with overexpression of human Aβ, and such mice are therefore possible to use in biomedicine to model the key features of AD. The transgenic mouse line APPswe/PS1dE9 is widely used as an animal model to study the molecular mechanisms of AD. A study was made to characterize the APPswe/PS1dE9/Blg subline, which was obtained by crossing APPswe/PS1dE9 mice on a CH3 genetic background with C57Bl6/Chg mice. No difference in offspring's survival and fertility was observed in the subline compared to wild-type control mice. Histological analysis of the brain in the APPswe/PS1dE9/Blg line confirmed the main neuromorphological features of AD and showed that amyloid plaques progressively increase in number and size during aging. The APPswe/PS1dE9/Blg line was assumed to provide a convenient model for developing therapeutic strategies to slow down AD progression.

A biotechnology for personalized ex vivo gene therapy based on molecular genomic balancing of hematopoietic stem cell (HSC) chromatin with nucleosome monomers of human genomic DNA (hDNA nmr ) has been developed and implemented in the clinic to change (to "correct") mutant chromosome loci genomes of dominant HSC clones that form mono- and oligoclonal hematopoiesis during aging and major (oncological, cardiovascular, neurodegenerative and autoimmune) fatal immune-mediated diseases of civilization. A fundamentally new biotechnological approach has been applied to the delivery of genetic material into eukaryotic stem and progenitor cells by establishing an artificial "recombinogenic situation" in them to induce homologous recombination (equivalent replacement) of mutant DNA regions with healthy hDNA nmr . In experimental preclinical trials, the effectiveness of genomic balancing technology has been proven to reduce the risk of sudden death in old animals and to increase the lifespan of outbred mice by 30% and Wistar rats by 57%. The improvement in their quality of life, compared with the control, is explained by an increase in the telomeric regions of the HSCs and HPCs chromosomes by 1.5-2 times. The potential of the technology to slow down the hereditary neurodegenerative diseases on the model of amyotrophic lateral sclerosis is shown. The effectiveness of this technology in clinical practice is presented on the example of a terminal patient with stage 4 neuroendocrine cancer. This technology used in the treatment of a number of oncological, neurodegenerative, autoimmune and hereditary diseases with clonal hematopoiesis is able to arrest the progression of the disease, prevent its recurrence, prolong the active life of a person, increase the average life expectancy and prevent sudden death., (Copyright © 2023. Published by Elsevier Inc.)

In the presented paper, we studied bilayer CVD graphene transferred to a langasite substrate and irradiated with a focused electron beam through a layer of polymethyl methacrylate (PMMA). Changes in the Raman spectra and an increase in the electrical resistance of bigraphene after irradiation indicate a local phase transition associated with graphene diamondization. The results are explained in the framework of the theory of a chemically induced phase transition of bilayer graphene to diamane, which can be associated with the release of hydrogen and oxygen atoms from PMMA and langasite due to the "knock-on" effect, respectively, upon irradiation of the structure with an electron beam. Theoretical calculations of the modified structure of bigraphene on langasite and the experimental evaluation of sp 3 -hybridized carbon fraction indicate the formation of diamane nanoclusters in the bigraphene irradiated regions. This result can be considered as the first realization of local tunable bilayer graphene diamondization.

In this study the preparation of hybrid materials based on reduced graphene oxide (rGO) and conjugated copolymers is reported. By tuning the number and arrangement of thiophenes in the main chain (indacenothiophene or indacenothienothiophene) and the nature of the polymer acceptor (difluoro benzothiadiazole or diketopyrrolopyrrole) semiconducting copolymers were synthesized through Stille aromatic coupling and characterized to determine their molecular characteristics. The graphene oxide was synthesized using the Staudenmaier method and was further modified to reduced graphene oxide prior to structural characterization. Various mixtures with different rGO quantities and conjugated copolymers were prepared to determine the optoelectronic, thermal and morphological properties. An increase in the maximum absorbance ranging from 3 to 6 nm for all hybrid materials irrespective of the rGO concentration, when compared to the pristine conjugated copolymers, was estimated through the UV-Vis spectroscopy indicating a differentiation on the optical properties. Through voltammetric experiments the oxidation and reduction potentials were determined and the calculated HOMO and LUMO levels revealed a decrease on the electrochemical energy gap for low rGO concentrations. The study indicates the potential of the hybrid materials consisting of graphene oxide and high band gap conjugated copolymers for applications related to organic solar cells.

The results of a systematic study on the adsorption of polylysine molecules of different lengths on the surface of a 1,2-dimyristoyl- sn -glycero-3-phospho-L-serine (DMPS) monolayer in the liquid (LE) and condensed (LC) states are presented. A compressibility diagram and the Volta potential were recorded with the Langmuir monolayer technique and further analyzed with the empirical approach. The structure of the monolayer films with adsorbed polypeptides was studied with synchrotron X-ray reflectometry. Two- and three-layer slab models describe the reflectivity data fairly well and reveal both the significant structural changes and the dehydration of the polar groups induced by all polylysines used at the maximal coverage of the monolayer interface in both the LE and LC states. On the one hand, in the LE phase of the monolayer (area per molecule A ≅ 70 Ǻ 2 ), the integrated electron density of the lipid headgroup region is approximately half the density contained in the clean monolayer. This indicates both significant compaction and dehydration in the polar groups of the lipids, caused by the adsorption of polypeptides. On the other hand, in the LC state (A ≅ 40 Ǻ 2 ), the degree of the hydration of the polar region is similar to that for the initial DMPS monolayer. However, both the electron density and the thickness of the head group region differ significantly from the values of these parameters for the clean monolayer in the LC state.