Search

Simple Summary: The last decade has seen dramatic changes in cancer treatment. Various methods of the immunotherapy of solid tumors, including treatment with targeted monoclonal antibodies, such as immune checkpoint inhibitors, bi- or trispecific immune cell enhancers, and antibody derivatives (e.g., antibody–drug conjugates), in addition to adoptive cell transfer or cell therapy, are being actively developed. A number of these approaches target tumor cells directly, while several other strategies aim to neutralize immunosuppressive elements in the tumor microenvironment (TME) and transform TME from immunologically "cold" to "hot". Although many of these approaches have received clinical approval, each has inherent limitations that are considered in this review. Additionally, we discuss recent innovations in immunotherapy to improve clinical efficacy in solid tumors and strategies to overcome the limitations of various immunotherapy. In recent years, the arrival of the immunotherapy industry has introduced the possibility of providing transformative, durable, and potentially curative outcomes for various forms of malignancies. However, further research has shown that there are a number of issues that significantly reduce the effectiveness of immunotherapy, especially in solid tumors. First of all, these problems are related to the protective mechanisms of the tumor and its microenvironment. Currently, major efforts are focused on overcoming protective mechanisms by using different adoptive cell therapy variants and modifications of genetically engineered constructs. In addition, a complex workforce is required to develop and implement these treatments. To overcome these significant challenges, innovative strategies and approaches are necessary to engineer more powerful variations of immunotherapy with improved antitumor activity and decreased toxicity. In this review, we discuss recent innovations in immunotherapy aimed at improving clinical efficacy in solid tumors, as well as strategies to overcome the limitations of various immunotherapies. [ABSTRACT FROM AUTHOR]

A flow-through biosensor system for the determination of uric acid was developed on the platform of flow-through electrochemical cell manufactured by 3D printing from poly(lactic acid) and equipped with a modified screen-printed graphite electrode (SPE). Uricase was immobilized to the inner surface of a replaceable reactor chamber. Its working volume was reduced to 10 μL against a previously reported similar cell. SPE was modified independently of the enzyme reactor with carbon black, pillar[5]arene, poly(amidoamine) dendrimers based on the p-tert-butylthiacalix[4]arene (PAMAM-calix-dendrimers) platform and electropolymerized 3,7-bis(4-aminophenylamino) phenothiazin-5-ium chloride. Introduction of the PAMAM-calix-dendrimers into the electrode coating led to a fivefold increase in the redox currents of the electroactive polymer. It was found that higher generations of the PAMAM-calix-dendrimers led to a greater increase in the currents measured. Coatings consisted of products of the electropolymerization of the phenothiazine with implemented pillar[5]arene and PAMAM-calix-dendrimers showing high efficiency in the electrochemical reduction of hydrogen peroxide that was formed in the enzymatic oxidation of uric acid. The presence of PAMAM-calix-dendrimer G2 in the coating increased the redox signal related to the uric acid assay by more than 1.5 times. The biosensor system was successfully applied for the enzymatic determination of uric acid in chronoamperometric mode. The following optimal parameters for the chronoamperometric determination of uric acid in flow-through conditions were established: pH 8.0, flow rate 0.2 mL·min−1, 5 U of uricase per reactor. Under these conditions, the biosensor system made it possible to determine from 10 nM to 20 μM of uric acid with the limit of detection (LOD) of 4 nM. Glucose (up to 1 mM), dopamine (up to 0.5 mM), and ascorbic acid (up to 50 μM) did not affect the signal of the biosensor toward uric acid. The biosensor was tested on spiked artificial urine samples, and showed 101% recovery for tenfold diluted samples. The ease of assembly of the flow cell and the low cost of the replacement parts make for a promising future application of the biosensor system in routine clinical analyses. [ABSTRACT FROM AUTHOR]

New solvent systems for selective separation of palladium from nuclear wastes represent a prospective way to reduce the total waste volume and induce this metal's extraction. For this purpose, the potential of modern green solvent room-temperature ionic liquid was assessed with diamide-type extractants based on N-heterocycles and S-donating thiodiglicolic acid. The N-donating heterocyclic extractants demonstrate structure-dependent high selectivity toward palladium in the presence of various impurity metals (such as Zr, Cs, Sr, Mo, Ce, Fe, and Cr) from spent nuclear fuel. Palladium is extracted into the organic phase quite selectively with a separation factor greater than a thousand for all extractants. Ionic liquid media are capable of selective palladium separation from platinum group metals and synergetically increase the selectivity of the extractants. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases and Alzheimer's disease (AD), as one of the most common causes of dementia, result in progressive losses of cholinergic neurons and a reduction in the presynaptic markers of the cholinergic system. These consequences can be compensated by the inhibition of acetylcholinesterase (AChE) followed by a decrease in the rate of acetylcholine hydrolysis. For this reason, anticholinesterase drugs with reversible inhibition effects are applied for the administration of neurodegenerative diseases. Their overdosage, variation in efficiency and recommendation of an individual daily dose require simple and reliable measurement devices capable of the assessment of the drug concentration in biological fluids and medications. In this review, the performance of electrochemical biosensors utilizing immobilized cholinesterases is considered to show their advantages and drawbacks in the determination of anticholinesterase drugs. In addition, common drugs applied in treating neurodegenerative diseases are briefly characterized. The immobilization of enzymes, nature of the signal recorded and its dependence on the transducer modification are considered and the analytical characteristics of appropriate biosensors are summarized for donepezil, huperzine A, rivastigmine, eserine and galantamine as common anti-dementia drugs. Finally, the prospects for the application of AChE-based biosensors in clinical practice are discussed. [ABSTRACT FROM AUTHOR]

Flexible electronics have sparked significant interest in the development of electrically conductive polymer-based composite materials. While efforts are being made to fabricate these composites through laser integration techniques, a versatile methodology applicable to a broad range of thermoplastic polymers remains elusive. Moreover, the underlying mechanisms driving the formation of such composites are not thoroughly understood. Addressing this knowledge gap, our research focuses on the core processes determining the integration of reduced graphene oxide (rGO) with polymers to engineer coatings that are not only flexible and robust but also exhibit electrical conductivity. Notably, we have identified a particular range of laser power densities (between 0.8 and 1.83 kW/cm2), which enables obtaining graphene polymer composite coatings for a large set of thermoplastic polymers. These laser parameters are primarily defined by the thermal properties of the polymers as confirmed by thermal analysis as well as numerical simulations. Scanning electron microscopy with elemental analysis and X-ray photoelectron spectroscopy showed that conductivity can be achieved by two mechanisms—rGO integration and polymer carbonization. Additionally, high-speed videos allowed us to capture the graphene oxide (GO) modification and melt pool formation during laser processing. The cross-sectional analysis of the laser-processed samples showed that the convective flows are present in the polymer substrate explaining the observed behavior. Moreover, the practical application of our research is exemplified through the successful assembly of a conductive wristband for wearable devices. Our study not only fills a critical knowledge gap but also offers a tangible illustration of the potential impact of laser-induced rGO-polymer integration in materials science and engineering applications. [ABSTRACT FROM AUTHOR]

To examine the scope of the abnormal aryl strengthening effect (an increase in the extraction of metal ions when an aromatic substituent is introduced into the amide group) on f-metal extraction, a series of tetradentate diamide-type extragents bearing electron-withdrawing pyridine rings in amide moieties of the molecules were tested. The solvent extraction of Am(III)/Eu(III) pairs was investigated under various conditions, the solution chemistry of the lanthanide-extragents systems was studied, and the bonding constants were calculated for complexes of Eu(III) and Tb(III) ions with diamides. The photophysical properties of chemically synthesized ligand/metal (LM) complexes with various LM compositions were additionally studied in depth. The replacement of a phenyl ring by a pyridine one led to a critical reduction in metal affinity, showing the major contribution of electronic nature to the abnormal aryl strengthening effect. However, the pyridine group in the amide side chain provided additional coordination positions for metal ion binding; corresponding complexes with LM2 composition were detected in the system and their stability was calculated. Due to the low stability of the corresponding LM2 complexes, chemical synthesis of the complexes led to the formation of only one metal-containing species with LM composition. The luminescence spectra of europium and terbium complexes of the LM composition were studied. Differences were discovered in the luminescence excitation spectra of europium and terbium complexes with the same ligand. The luminescence quantum yields and luminescence lifetimes of solutions of europium and terbium complexes were determined. [ABSTRACT FROM AUTHOR]

Platinum-based thin films are widely used to create microelectronic devices operating at temperatures above 500 °C. One of the most effective ways to increase the high-temperature stability of platinum-based films involves incorporating refractory metal oxides (e.g., ZrO2, HfO2). In such structures, refractory oxide is located along the metal grain boundaries and hinders the mobility of Pt atoms. However, the effect of annealing conditions on the morphology and functional properties of such multiphase systems is rarely studied. Here, we show that the two-step annealing of 250-nm-thick Pt-Rh/Zr multilayer films instead of the widely used isothermal annealing leads to a more uniform film morphology without voids and hillocks. The composition and morphology of as-deposited and annealed films were investigated using X-ray diffraction and scanning electron microscopy, combined with energy-dispersive X-ray spectroscopy. At the first annealing step at 450 °C, zirconium oxidation was observed. The second high-temperature annealing at 800–1000 °C resulted in the recrystallization of the Pt-Rh alloy. In comparison to the one-step annealing of Pt-Rh and Pt-Rh/Zr films, after two-step annealing, the metal phase in the Pt-Rh/Zr films has a smaller grain size and a less pronounced texture in the <111> direction, manifesting enhanced high-temperature stability. After two-step annealing at 450/900 °C, the Pt-Rh/Zr thin film possessed a grain size of 60 ± 27 nm and a resistivity of 17 × 10−6 Ω·m. The proposed annealing protocol can be used to create thin-film MEMS devices for operation at elevated temperatures, e.g., microheater-based gas sensors. [ABSTRACT FROM AUTHOR]

The paper is devoted to the formal description of the running time of the user task on some virtual nodes in the computing network. Based on the probability theory framework, this time represents a random value with a finite mean and variance. For any class of user task, these moments are the functions of the node resources, task numerical characteristics, and the parameters of the current node state. These functions of the vector arguments can be treated as some surfaces in the multidimensional Euclidean spaces, so the proposed models are called the stochastic time complexity surfaces. The paper also presents a class of functions suitable for the description of both the mean and variance. They contain unknown parameters which should be estimated. The article includes the statement of the parameter identification problem given the statistical results of the node stress testing, recommendations concerning the test planning, and preprocessing of the raw experiment data. To illustrate the performance of the proposed model, the authors design it for an actual database application—the prototype of the passengers' personal data anonymization system. Its application functions are classified into two user task classes: the data anonymization procedures and fulfillment of the statistical queries. The authors identify the stochastic time complexity surfaces for both task types. The additional testing experiments confirm the high performance of the suggested model and its applicability to the solution of the practical providers' problems. [ABSTRACT FROM AUTHOR]

Regeneration of periodontal tissues requires an integrated approach to the restoration of the periodontal ligament, cementum, and alveolar bone surrounding the teeth. Current strategies in endogenous regenerative dentistry widely use biomaterials, in particular the decellularized extracellular matrix (dECM), to facilitate the recruitment of populations of resident cells into damaged tissues and stimulate their proliferation and differentiation. The purpose of our study was to evaluate the effect of the exogenous components of the extracellular matrix (hyaluronic acid, laminin, fibronectin) on the differentiation of periodontal ligament stem cells (PDLSCs) cultured with dECM (combinations of decellularized tooth matrices and periodontal ligament) in a 3D collagen I hydrogel. The immunohistochemical expression of various markers in PDLSCs was assessed quantitatively and semi-quantitatively on paraffin sections. The results showed that PDLSCs cultured under these conditions for 14 days exhibited phenotypic characteristics consistent with osteoblast-like and odontoblast-like cells. This potential has been demonstrated by the expression of osteogenic differentiation markers (OC, OPN, ALP) and odontogenic markers (DSPP). This phenomenon corresponds to the in vivo state of the periodontal ligament, in which cells at the interface between bone and cementum tend to differentiate into osteoblasts or cementoblasts. The addition of fibronectin to the dECM most effectively induces the differentiation of PDLSCs into osteoblast-like and odontoblast-like cells under 3D culture conditions. Therefore, this bioengineered construct has a high potential for future use in periodontal tissue regeneration. [ABSTRACT FROM AUTHOR]

Transport of vesicles and organelles inside cells consists of constant-speed bidirectional movement along cytoskeletal filaments interspersed by periods of idling. This transport shows many features of anomalous diffusion. In this paper, we develop a non-Markovian persistent random walk model for intracellular transport that incorporates the removal rate of organelles. The model consists of two active states with different speeds and one resting state. The organelle transitions between states with switching rates that depend on the residence time the organelle spends in each state. The mesoscopic master equations that describe the average densities of intracellular transport in each of the three states are the main results of the paper. We also derive ordinary differential equations for the dynamics for the first and second moments of the organelles' position along the cell. Furthermore, we analyse models with power-law distributed random times, which reveal the prevalence of the Mittag-Leffler resting state and its contribution to subdiffusive and superdiffusive behaviour. Finally, we demonstrate a non-Markovian non-additivity effect when the switching rates and transport characteristics depend on the rate of organelles removal. The analytical calculations are in good agreement with numerical Monte Carlo simulations. Our results shed light on the dynamics of intracellular transport and emphasise the effects of rest times on the persistence of random walks in complex biological systems. [ABSTRACT FROM AUTHOR]

In this paper we describe the results of the influence of temperature in the range of 280–340 K on the luminescence of bimetallic Eu/Tb complexes with N-heterocyclic ligand L based on 2,2′-bipyridyldicarboxylic acid in acetonitrile. The experiments were carried out for systems with various Eu/Tb ratios. The stability of the complexes of the ligand L with metal M (Eu or Tb) was determined using spectrophotometric titration in acetonitrile solutions. The LM complexes' stability constants were found to be typical for these systems; however, the stability of Eu complex is slightly higher than that for Tb. Along with rising temperature, we observed a decrease in Tb emission intensity and, at the same time, an enhancement in Eu luminescence. An explanation of Eu luminescence enhancement involves the appearance of charge transfer states, bands of which can be observed in the Eu luminescence excitation spectra as difference spectra measured with two close temperatures. The unusual Eu luminescence enhancement upon heating was observed for the first time for the complex with tetradentate O,N-type heterocyclic diamide ligand L, while an inverse phenomenon was observed with the Tb luminescence. The Eu luminescence enhancement was found earlier for various carboxylate complex salts, but not for heterocyclic coordination complexes. This allows the construction of a ratiometric luminescent thermometer in the range of 280–340 K using the ratio of luminescence intensities for Eu and Tb. The stability constants for the individual Eu and Tb complexes help us to understand the equilibrium in L:Tb:Eu complex system and shed light on plausible speciation in solution. [ABSTRACT FROM AUTHOR]

We designed 0D, 1D, and 2D supramolecular assemblies made of diaryliodonium salts (functioning as double σ-hole donors) and carboxylates (as σ-hole acceptors). The association was based on two charge-supported halogen bonds (XB), which occurred between IIII sites of the iodonium cations and the carboxylate anions. The sequential introduction of the carboxylic groups in the aryl ring of the benzoic acid added a dimension to the 0D supramolecular organization of the benzoate, which furnished 1D-chained and 2D-layered structures when terephthalate and trimesate anions, correspondingly, were applied as XB acceptors. The structure-directing XB were studied using DFT calculations under periodic boundary conditions and were followed by the one-electron-potential analysis and the Bader atoms-in-molecules topological analysis of electron density. These theoretical methods confirmed the existence of the XB and verified the philicities of the interaction partners in the designed solid-state structures. [ABSTRACT FROM AUTHOR]

Sodium-ion batteries (SIBs) have demonstrated noticeable development since the 2010s, being complementary to the lithium-ion technology in predominantly large-scale application niches. The projected SIB market growth will inevitably lead to the generation of tons of spent cells, posing a notorious issue for proper battery lifecycle management, which requires both the establishment of a regulatory framework and development of technologies for recovery of valuable elements from battery waste. While lithium-ion batteries are mainly based on layered oxides and lithium iron phosphate chemistries, the variety of sodium-ion batteries is much more diverse, extended by a number of other polyanionic families (crystal types), such as NASICON (Na3V2(PO4)3), Na3V2(PO4)2F3−yOy, (0 ≤ y ≤ 2), KTiOPO4-type AVPO4X (A—alkali metal cation, X = O, F) and β-NaVP2O7, with all of them relying on vanadium and phosphorous—critical elements in a myriad of industrial processes and technologies. Overall, the greater chemical complexity of these vanadium-containing phosphate materials highlights the need for designing specific recycling approaches based on distinctive features of vanadium and phosphorus solution chemistry, fine-tuned for the particular electrodes used. In this paper, an overview of recycling methods is presented with a focus on emerging chemistries for SIBs. [ABSTRACT FROM AUTHOR]

Lap-welded joints between Ti–6Al–4V and Al–4Cu–1Mg were obtained using water-cooling-bath friction stir welding at different FSW tool rotation rates. The increase in the tool rotation rate from 350 to 375 RPM leads to better plasticization of the titanium alloy, elimination of stir zone defects, better interlocking and bonding with the aluminum alloy as well as the formation of intermetallic Al–Ti compounds (IMC), preferentially of the Al3Ti type. Shear-loading testing showed the best result was at the level of 3000 N with 2 mm of displacement. Increasing the FSW tool rotation rate to 400 and 450 RPM resulted in the formation of more IMCs, which had a detrimental effect on both maximum load and displacement achieved in the shear tests. [ABSTRACT FROM AUTHOR]

This study focused on a potential application of electrically conductive, biocompatible, bioresorbable fibers for tubular conduits aimed at the regeneration of peripheral nerves. The conducting, mechanical, and biological properties of composite fibers based on chitosan and single-walled carbon nanotubes were investigated in this paper. It was shown that introducing 0.5 wt.% of SWCNT into the composite fibers facilitated the formation of a denser fiber structure, resulting in improved strength (σ = 260 MPa) and elastic (E = 14 GPa) characteristics. Additionally, the composite fibers were found to be biocompatible and did not cause significant inflammation or deformation during in vivo studies. A thin layer of connective tissue formed around the fiber. [ABSTRACT FROM AUTHOR]

The paradigm of drug delivery via particulate formulations is one of the leading ideas that enable overcoming limitations of traditional chemotherapeutic agents. The trend toward more complex multifunctional drug carriers is well-traced in the literature. Nowadays, the prospectiveness of stimuli-responsive systems capable of controlled cargo release in the lesion nidus is widely accepted. Both endogenous and exogenous stimuli are employed for this purpose; however, endogenous pH is the most common trigger. Unfortunately, scientists encounter multiple challenges on the way to the implementation of this idea related to the vehicles' accumulation in off-target tissues, their immunogenicity, the complexity of drug delivery to intracellular targets, and finally, the difficulties in the fabrication of carriers matching all imposed requirements. Here, we discuss fundamental strategies for pH-responsive drug delivery, as well as limitations related to such carriers' application, and reveal the main problems, weaknesses, and reasons for poor clinical results. Moreover, we attempted to formulate the profiles of an "ideal" drug carrier in the frame of different strategies drawing on the example of metal-comprising materials and considered recently published studies through the lens of these profiles. We believe that this approach will facilitate the formulation of the main challenges facing researchers and the identification of the most promising trends in technology development. [ABSTRACT FROM AUTHOR]

The regeneration of periodontal tissues is a decisive factor in the treatment of periodontitis. Currently, to achieve complete periodontal regeneration, many studies have evaluated the effectiveness of decellularized tissue-engineered constructs on periodontal regeneration. We studied the possibilities of osteogenic and odontogenic differentiation of periodontal progenitor and stem cells (SCs) of the periosteum and periodontal ligament, in decellularized tooth matrix (dTM) and periodontal ligament (dPDL), in 2D and 3D culture. The cell culture of periodontal cells without decellularized matrices was used as control. On the 14th day of cultivation of PDLSCs, PSCs, and PDLSCs + PSCs on dTM and/or dPDL scaffolds in 2D conditions, in all scaffold variants, a dense monolayer of spindle-shaped cells was intensely stained for markers of osteogenic differentiation, such as osteopontin and osteocalcin. Periodontal cells in the collagen I hydrogel (3D-dimensional culture) were more diverse in shape and, in combination of dTM and dPDL, in addition to osteogenic expression, expressed dentin sialophosphoprotein, an odontogenic differentiation marker. Thus, collagen I hydrogel contributed to the formation of conditions similar to those in vivo, and the combination of dTM with dPDL apparently formed a microenvironment that promoted osteogenic and odontogenic differentiation of periodontal cells. [ABSTRACT FROM AUTHOR]

A solid-contact potentiometric sensor has been developed on the basis of glassy carbon electrode covered with electropolymerized polyaniline and alternatively layered pillar[6]arene and Cu2+ ions films. The assembly of the surface layer was confirmed by surface plasmon resonance measurements. The number of deposited layers was selected to reach better analytical characteristics for Cu2+ determination. It was shown that better results were achieved by using five layers, the upper one consisting of the macrocycle. The addition of covering layers for polyelectrolytes (Nafion, poly(styrene sulfonate)) and Cu2+ ions did not improve sensor performance. The potentiometric sensor made it possible to determine Cu2+ ions in neutral and weakly acidic media with a linear range of the concentrations, from 3.0 μM to 10.0 mM (limit of detection 3.0 μM). The applicability of the sensor in real sample assays was confirmed by the determination of Cu2+ ions in copper vitriol, Bordeaux mixture, and polyvitamin-mineral pills of "Complivit" during an atomic emission spectroscopy analysis. [ABSTRACT FROM AUTHOR]

Hybrid donor extractants are a promising class of compounds for the separation of trivalent actinides and lanthanides. In this paper, we present a new ligand from the bipyridyl-dicarboxylic acid diamide family—N,N'-diethyl-N,N'-bis(2,4,5-trimethylphenyl)-[2,2'-bipyridine]-6,6'-dicarboxamide. The synthesis of N-ethyl-2,4,5-trimethylaniline from pseudocumene by selective acetylation is presented. The target ligand was obtained using this aminylene. Chemical synthesis of its complexes with Ln(NO3)3 and their spectroscopic analysis showed that the structure of the complexes is near to the corresponding structures of well-known di-methylated dianilides. A series of studies on the photophysical, complexing, and extraction properties of this ligand and its complexes were carried out. It was shown that the extraction system based on this ligand can selectively isolate americium from the solution of high-level waste imitator. [ABSTRACT FROM AUTHOR]

The paper presents the results of the petrographic and geochemical studies of igneous rocks of the Medvedev and Taezhniy massifs, including their first absolute dating. The massifs are located in central Nimnyr block of the n shield within the Leglier ore cluster of the Evotinskiy ore district (Southeast Russia, Aldan Shield). For the first time, the three-phase structure of the Medvedev massif has been defined, as observed in our expedition and petrographic studies. Rocks from the three phases of the Medvedev massif include quartz syenites, syenites, and monzonites, and rocks from the two phases of the Taezhniy massif include quartz monzonites and syenites. Geochemically, the rocks are close to volcanic island arcs, the formation of which was related by subducted oceanic crust of the Mongol–Okhotsk Ocean. The defined duality of the geochemical compositions of the igneous rocks of the massifs may be due to the presence of both mantle and crustal sources; however, it is most likely that these rocks resulted from the melting of a mixed mantle source or the latter was contaminated by the crust with further differentiation of melts in intermediate crust chambers. Additionally, geochemical characteristics suggest that the analyzed rocks are close to latite and shoshonite derivatives and can be considered as part of the monzonite–syenite formation type. The first identified periods of formation of igneous rocks in the Medvedev massif are 122.0–118.0 Ma and Taezhniy 117.5–114.5 Ma, which correspond to the Early Cretaceous (Aptian). [ABSTRACT FROM AUTHOR]

There are currently no effective biomarkers for prognosis and optimal treatment selection to improve non-small cell lung cancer (NSCLC) survival outcomes. This study further validated a seven-gene panel for diagnosis and prognosis of NSCLC using RNA sequencing and proteomic profiles of patient tumors. Within the seven-gene panel, ZNF71 expression combined with dendritic cell activities defined NSCLC patient subgroups (n = 966) with distinct survival outcomes (p = 0.04, Kaplan–Meier analysis). ZNF71 expression was significantly associated with the activities of natural killer cells (p = 0.014) and natural killer T cells (p = 0.003) in NSCLC patient tumors (n = 1016) using Chi-squared tests. Overexpression of ZNF71 resulted in decreased expression of multiple components of the intracellular intrinsic and innate immune systems, including dsRNA and dsDNA sensors. Multi-omics networks of ZNF71 and the intracellular intrinsic and innate immune systems were computed as relevant to NSCLC tumorigenesis, proliferation, and survival using patient clinical information and in-vitro CRISPR-Cas9/RNAi screening data. From these networks, pan-sensitive and pan-resistant genes to 21 NCCN-recommended drugs for treating NSCLC were selected. Based on the gene associations with patient survival and in-vitro CRISPR-Cas9, RNAi, and drug screening data, MEK1/2 inhibitors PD-198306 and U-0126, VEGFR inhibitor ZM-306416, and IGF-1R inhibitor PQ-401 were discovered as potential targeted therapy that may also induce an immune response for treating NSCLC. [ABSTRACT FROM AUTHOR]

Fast and reliable determination of enzyme inhibitors are of great importance in environmental monitoring and biomedicine because of the high biological activity and toxicity of such species and the necessity of their reliable assessment in many media. In this work, a flow-through biosensor has been developed and produced by 3D printing from poly(lactic acid). Acetylcholinesterase from an electric eel was immobilized on the inner walls of the reactor cell. The concentration of thiocholine formed in enzymatic hydrolysis of the substrate was monitored amperometrically with a screen-printed carbon electrode modified with carbon black particles, pillar[5]arene, electropolymerized Methylene blue and thionine. In the presence of thiocholine, the cathodic current at −0.25 V decreased because of an alternative chemical reaction of the macrocycle. The conditions of enzyme immobilization and signal measurements were optimized and the performance of the biosensor was assessed in the determination of reversible (donepezil, berberine) and irreversible (carbofuran) inhibitors. In the optimal conditions, the flow-through biosensor made it possible to determine 1.0 nM–1.0 μM donepezil, 1.0 μM–1.0 mM berberine and 10 nM to 0.1 μM carbofuran. The AChE biosensor was tested on spiked samples of artificial urine for drugs and peanuts for carbofuran. Possible interference of the sample components was eliminated by dilution of the samples with phosphate buffer. Easy mounting, low cost of replaceable parts of the cell and satisfactory analytical and metrological characteristics made the biosensor a promising future application as a point-of-care or point-of-demand device outside of a chemical laboratory. [ABSTRACT FROM AUTHOR]

There is an unmet clinical need to identify patients with early-stage non-small cell lung cancer (NSCLC) who are likely to develop recurrence and to predict their therapeutic responses. Our previous study developed a qRT-PCR-based seven-gene microfluidic assay to predict the recurrence risk and the clinical benefits of chemotherapy. This study showed it was feasible to apply this seven-gene panel in RNA sequencing profiles of The Cancer Genome Atlas (TCGA) NSCLC patients (n = 923) in randomly partitioned feasibility-training and validation sets (p < 0.05, Kaplan–Meier analysis). Using Boolean implication networks, DNA copy number variation-mediated transcriptional regulatory network of the seven-gene signature was identified in multiple NSCLC cohorts (n = 371). The multi-omics network genes, including PD-L1, were significantly correlated with immune infiltration and drug response to 10 commonly used drugs for treating NSCLC. ZNF71 protein expression was positively correlated with epithelial markers and was negatively correlated with mesenchymal markers in NSCLC cell lines in Western blots. PI3K was identified as a relevant pathway of proliferation networks involving ZNF71 and its isoforms formulated with CRISPR-Cas9 and RNA interference (RNAi) profiles. Based on the gene expression of the multi-omics network, repositioning drugs were identified for NSCLC treatment. [ABSTRACT FROM AUTHOR]

Water-soluble complexes of N-vinylpyrrolidone/N-vinylamine copolymers with lactones of D-glucuronic acid were obtained and characterized by chromatographic, spectral, and hydrodynamic methods. The complexes efficiently inhibited the enzyme β-glucuronidase that causes the appearance of bladder tumors. The products demonstrated prolonged action and were stable during storage. [ABSTRACT FROM AUTHOR]

An approach called cell-free therapy has rapidly developed in regenerative medicine over the past decade. Understanding the molecular mechanisms and signaling pathways involved in the internal potential of tissue repair inspires the development of new strategies aimed at controlling and enhancing these processes during regeneration. The use of stem cell mobilization, or homing for regeneration based on endogenous healing mechanisms, prompted a new concept in regenerative medicine: endogenous regenerative medicine. The application of cell-free therapeutic agents leading to the recruitment/homing of endogenous stem cells has advantages in overcoming the limitations and risks associated with cell therapy. In this review, we discuss the potential of cell-free products such as the decellularized extracellular matrix, growth factors, extracellular vesicles and miRNAs in endogenous bone and dental regeneration. [ABSTRACT FROM AUTHOR]

The response of ferrofluids to a high-amplitude AC magnetic field is important for several applications including magnetic hyperthermia and biodetection. In computer simulations of the dynamic susceptibility of a ferrofluid outside the linear response region, there are several problems associated with the fact that an increase in the frequency of the AC field leads to the appearance of additional computational errors, which can even lead to unphysical results. In this article, we study the dependence of the computational error arising in the computer simulation of the dynamic susceptibility on the input parameters of the numerical algorithm: the length of the time step, the total number of computer simulation periods, and averaging period. Computer simulation is carried out using the Langevin dynamics method and takes Brownian rotational relaxation of magnetic particles and interparticle interactions into account. The reference theory [Yoshida T.; Enpuku K. Jap. J. Ap. Phys. 2009] is used to estimate computational error. As a result, we give practical recommendations for choosing the optimal input parameters of the numerical algorithm, which make it possible to obtain reliable results of the dynamic susceptibility of a ferrofluid in a high-amplitude AC field in a wide frequency range. [ABSTRACT FROM AUTHOR]

The size-dependent properties of magnetic nanoparticles (MNP) are the major characteristics, determining MNP application in modern technologies and bio-medical techniques. Direct measurements of the nanosized particles, involved in intensive Brownian motion, are very complicated; so the correct mathematical methods for the experimental data processing enable to successfully predict the properties of MNP suspensions. In the present paper, we describe the fast numerical algorithm allowing to get the distribution over the relaxation time of MNP magnetic moments in ferrofluids. The algorithm is based on numerical fitting of the experimentally measured frequency spectra of the initial dynamic magnetic susceptibility. The efficiency of the algorithm in the solution of the inverse problem of magnetic granulometry is substantiated by the computer experiments for mono- and bi-fractional ferrofluids. [ABSTRACT FROM AUTHOR]

Our previous study found that zinc finger protein 71 (ZNF71) mRNA expression was associated with chemosensitivity and its protein expression was prognostic of non-small-cell lung cancer (NSCLC). The Krüppel associated box (KRAB) transcriptional repression domain is commonly present in human zinc finger proteins, which are linked to imprinting, silencing of repetitive elements, proliferation, apoptosis, and cancer. This study revealed that ZNF71 KRAB had a significantly higher expression than the ZNF71 KRAB-less isoform in NSCLC tumors (n = 197) and cell lines (n = 117). Patients with higher ZNF71 KRAB expression had a significantly worse survival outcome than patients with lower ZNF71 KRAB expression (log-rank p = 0.04; hazard ratio (HR): 1.686 [1.026, 2.771]), whereas ZNF71 overall and KRAB-less expression levels were not prognostic in the same patient cohort. ZNF71 KRAB expression was associated with epithelial-to-mesenchymal transition (EMT) in both patient tumors and cell lines. ZNF71 KRAB was overexpressed in NSCLC cell lines resistant to docetaxel and paclitaxel treatment compared to chemo-sensitive cell lines, consistent with its association with poor prognosis in patients. Therefore, ZNF71 KRAB isoform is a more effective prognostic factor than ZNF71 overall and KRAB-less expression for NSCLC. Functional analysis using CRISPR-Cas9 and RNA interference (RNAi) screening data indicated that a knockdown/knockout of ZNF71 did not significantly affect NSCLC cell proliferation in vitro. [ABSTRACT FROM AUTHOR]

A measurement system for the detection of a low concentration of nanoparticles based on optical microcavities with whispering-gallery modes (WGMs) is developed and investigated. A novel method based on the WGM broadening allows us to increase the precision of concentration measurements up to 0.005 ppm for nanoparticles of a known size. We describe WGM microcavity manufacturing and quality control methods. The collective interaction process of suspended Ag nanoparticles in a liquid and TiO2 in the air with a microcavity surface is studied. [ABSTRACT FROM AUTHOR]

Ferrofluids have attracted considerable interest from researchers and engineers due to their rich set of unique physical properties that are valuable for many industrial and biomedical applications. Many phenomena and features of ferrofluids' behavior are determined by internal structural transformations in the ensembles of particles, which occur due to the magnetic interaction between the particles. An applied magnetic field induces formations, such as linear chains and bulk columns, that become elongated along the field. In turn, these structures dramatically change the rheological and other physical properties of these fluids. A deep and clear understanding of the main features and laws of the transformations is necessary for the understanding and explanation of the macroscopic properties and behavior of ferrofluids. In this paper, we present an overview of experimental and theoretical works on the internal transformations in these systems, as well as on the effect of the internal structures on the rheological effects in the fluids. [ABSTRACT FROM AUTHOR]

Whether the spring season brings additional pollution to the urban environment remains questionable for a megacity. Aerosol sampling and characterization was performed in the urban background of the Moscow megacity in spring 2017, in a period of a significant impact of mass advection from surrounding fire regions. Parametrization of Angstrom absorption exponent (AAE) on low and high values provides periods dominated by fossil fuel (FF) combustion and affected by biomass burning (BB), respectively. The period identification is supported by air mass transportation from the south of Russia through the regions where a number of fires were observed. Functionalities in entire aerosol composition, assigned to classes of organic, ionic compounds, and dust, are inferred by diffusion refection infrared Fourier transmission (FTIR) spectroscopy. Functional markers of urban transport emissions relate to modern engine technology and driving cycles. Regional BB functionalities indicate the fire impacts to the spring aerosol composition. The development of the advanced source apportionment for a megacity is performed by means of combined ambient FTIR data and statistical PCA analysis. PCA of FTIR spectral data differentiate daily aerosol chemistry by low and high AAE values, related to FF- and BB-affected spectral features. PC loadings of 58%, 21%, and 11% of variability reveal the functional factors of transport, biomass burning, biogenic, dust, and secondary aerosol spring source impacts. [ABSTRACT FROM AUTHOR]

We have synthesized and examined several complexes of lanthanides with diamides of 2,2′-bipyridyl-6,6′-dicarboxylic acid bearing various hetaryl-based side chains for the elucidation of the effect of the heterocycle on the structure and properties of the ligands. The multigram scale methods for the preparation of various N-alkyl-hetaryls and their diamides were developed. The solid state structure of 6-methyl-2-pyridylamide of 2,2′-bipyridyl-6,6′-dicarboxylic acid possesses a flat structure where the conformation is completely different from that previously observed for N-alkylated 2,2′-bipyridyl-6,6′-dicarboxamides and 2,6-pyridinedicarboxamides. The complexes of new ligands were synthesized and NMR and X-Ray studied their structure in solution and solid state. The results demonstrate that complexes possess the same structures both in solid state and in solution. Stability constants of the complexes were less when comparing with dimethyl-substituted diamides, but higher than for unsubstituted dianilide. Contrarily, the extraction ability of 2-pyridyl-diamide is significantly lower than for corresponding anilide. Specific interaction of extractant with solvent molecules, which is not available for electron-sink pyridine amides, can explain this. The luminescence of new Eu complexes was significantly higher than for all previously 2,2′-bipyridyl-6,6′-dicarboxamides and QY reaches 18%. Asymmetry ratios of Eu complexes were 25% higher when compared other complexes with 2,2′-bipyridyl-6,6′-dicarboxamides, which indicates large deviation from the inversion center. [ABSTRACT FROM AUTHOR]

In this study, we derived the equations describing the dynamics of a magnetic fluid in crossed magnetic fields (bias and alternating probe fields), considering the field dependence of the relaxation times, interparticle interactions, and demagnetizing field has been derived. For a monodisperse fluid, the dependence of the output signal on the bias field and the probe field frequency was constructed. Experimental studies were conducted in a frequency range up to 80 kHz for two samples of fluids based on magnetite nanoparticles and kerosene. The first sample had a narrow particle size distribution, low-energy magneto dipole interactions, and weak dispersion of dynamic susceptibility. The second sample had a broad particle size distribution, high-energy magneto dipole interactions, and strong dispersion of dynamic susceptibility. In the first case, the bias field led to the appearance of short chains. In the second case, we found quasi-spherical clusters with a characteristic size of 100 nm. The strong dependence of the output signal on the particle size allowed us to use the crossed field method to independently estimate the maximum diameter of the magnetic core of particles. [ABSTRACT FROM AUTHOR]

Water-soluble complexes of N-vinylpyrrolidone/N-vinylamine copolymers with lactones of D-glucuronic acid were obtained and characterized by chromatographic, spectral, and hydrodynamic methods. The complexes efficiently inhibited the enzyme β-glucuronidase that causes the appearance of bladder tumors. The products demonstrated prolonged action and were stable during storage.

There is an unmet clinical need to identify patients with early-stage non-small cell lung cancer (NSCLC) who are likely to develop recurrence and to predict their therapeutic responses. Our previous study developed a qRT-PCR-based seven-gene microfluidic assay to predict the recurrence risk and the clinical benefits of chemotherapy. This study showed it was feasible to apply this seven-gene panel in RNA sequencing profiles of The Cancer Genome Atlas (TCGA) NSCLC patients ( n = 923) in randomly partitioned feasibility-training and validation sets ( p < 0.05, Kaplan-Meier analysis). Using Boolean implication networks, DNA copy number variation-mediated transcriptional regulatory network of the seven-gene signature was identified in multiple NSCLC cohorts ( n = 371). The multi-omics network genes, including PD-L1 , were significantly correlated with immune infiltration and drug response to 10 commonly used drugs for treating NSCLC. ZNF71 protein expression was positively correlated with epithelial markers and was negatively correlated with mesenchymal markers in NSCLC cell lines in Western blots. PI3K was identified as a relevant pathway of proliferation networks involving ZNF71 and its isoforms formulated with CRISPR-Cas9 and RNA interference (RNAi) profiles. Based on the gene expression of the multi-omics network, repositioning drugs were identified for NSCLC treatment.

We have synthesized and examined several complexes of lanthanides with diamides of 2,2'-bipyridyl-6,6'-dicarboxylic acid bearing various hetaryl-based side chains for the elucidation of the effect of the heterocycle on the structure and properties of the ligands. The multigram scale methods for the preparation of various N -alkyl-hetaryls and their diamides were developed. The solid state structure of 6-methyl-2-pyridylamide of 2,2'-bipyridyl-6,6'-dicarboxylic acid possesses a flat structure where the conformation is completely different from that previously observed for N -alkylated 2,2'-bipyridyl-6,6'-dicarboxamides and 2,6-pyridinedicarboxamides. The complexes of new ligands were synthesized and NMR and X-Ray studied their structure in solution and solid state. The results demonstrate that complexes possess the same structures both in solid state and in solution. Stability constants of the complexes were less when comparing with dimethyl-substituted diamides, but higher than for unsubstituted dianilide. Contrarily, the extraction ability of 2-pyridyl-diamide is significantly lower than for corresponding anilide. Specific interaction of extractant with solvent molecules, which is not available for electron-sink pyridine amides, can explain this. The luminescence of new Eu complexes was significantly higher than for all previously 2,2'-bipyridyl-6,6'-dicarboxamides and QY reaches 18%. Asymmetry ratios of Eu complexes were 25% higher when compared other complexes with 2,2'-bipyridyl-6,6'-dicarboxamides, which indicates large deviation from the inversion center.