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Simple Summary: Large B-cell lymphoma (LBCL) is a type of blood cancer that can be challenging to treat, especially when it does not respond to standard chemotherapy or relapses after treatment. New therapies, such as CAR-T cells and bispecific antibodies, have shown promise in treating these cases. However, not all patients benefit equally from these treatments, highlighting the need for new ways to predict treatment response. This study focuses on the tumor microenvironment, which includes the immune cells and molecules surrounding the LBCL tumor cells. By understanding how this environment affects CAR-T and bispecific antibody treatment outcomes, this manuscript aims to identify factors that can help predict success or resistance to therapy. These insights could lead to more personalized treatment approaches and improved outcomes for patients with LBCL. T-cell redirecting therapies, which include chimeric antigen receptor T-cells (CAR-Ts) and bispecific antibodies (BSAs), have revolutionized the treatment of relapsed\refractory large B-cell lymphoma (LBCL). Expanding clinical experience with these advanced therapies shows the potential for the optimization of their use with combination or consolidation strategies, which necessitates the prognostic stratification of patients. While traditional clinical prognostic factors identified in the era of chemotherapy are characterized by limited value, the tumor microenvironment (TME) is becoming a new prognostic cluster. We examine how the heterogeneity of LBCL, characterized by variations in tumor parameters and differences in TME immune cell composition, immune checkpoint expression, and cytokine milieu, correlates with both positive responses and resistance to treatment. While classical parameters such as histological subtype, cell of origin, and target antigen expression lack proven prognostic value for T-cell redirecting therapies, the density and functional state of tumor-infiltrating lymphocytes, tumor-associated macrophages, and immune checkpoint molecules are shown to be critical determinants of therapeutic success, particularly in CAR-T therapy. We identify several gaps in the current knowledge and suggest that the insights gained from CAR-T experience could be instrumental in refining BSA applications. This report also highlights limitations in the current knowledge, as TME data derive from a limited number of registrational trials with varying methodologies, complicating cross-study comparisons and often focusing on immediate response metrics rather than long-term outcomes. By dissecting the complex interactions within the TME, this review aims to identify new prognostic factors and targets, ultimately fostering more effective and tailored treatment strategies for LBCL patients. [ABSTRACT FROM AUTHOR]

High-voltage transmission lines face significant challenges due to environmental exposure, including corona discharge, ice accretion, and corrosion, which impact their durability and operational efficiency. This study investigates the performance of hydrophilic and superhydrophilic organosilane coatings applied to high-voltage wires to address these issues. Using a combination of experimental setups simulating real-world conditions, we evaluated corona discharge losses, ice adhesion, and corrosion resistance on coated and uncoated wires. The results reveal that hydrophilic and superhydrophilic organosilane coatings offer a substantial reduction in corona discharge power losses, with a 25–60% decrease compared to bare wires. Additionally, the proposed hydrophilic coating exhibits ice adhesion characteristics similar to bare wires, in contrast to the higher ice adhesion observed for superhydrophilic samples. Corrosion tests further highlight the performance of the hydrophilic coating, which reduces corrosion currents by approximately threefold compared to bare wires, demonstrating enhanced protection and long-term stability. While superhydrophilic coatings offer some advantages in corona discharge reduction, their increased ice adhesion and higher corrosion rates limit their applicability. The hydrophilic organosilane coating thus emerges as the optimal tradeoff, balancing effective corona discharge mitigation, moderating ice adhesion, and enhancing corrosion resistance, making it a promising solution for improving the performance and longevity of high-voltage transmission lines. [ABSTRACT FROM AUTHOR]

Acute ischemic stroke with large vessel occlusion (LVO) continues to present a considerable challenge to global health, marked by substantial morbidity and mortality rates. Although definitive diagnostic markers exist in the form of neuroimaging, their expense, limited availability, and potential for diagnostic delay can often result in missed opportunities for life-saving interventions. Despite several past attempts, research efforts to date have been fraught with challenges likely due to multiple factors, such as the inclusion of diverse stroke types, variable onset intervals, differing pathobiologies, and a range of infarct sizes, all contributing to inconsistent circulating biomarker levels. In this context, microRNAs (miRNAs) have emerged as a promising biomarker, demonstrating potential as biomarkers across various diseases, including cancer, cardiovascular conditions, and neurological disorders. These circulating miRNAs embody a wide spectrum of pathophysiological processes, encompassing cell death, inflammation, angiogenesis, neuroprotection, brain plasticity, and blood–brain barrier integrity. This pilot study explores the utility of circulating exosome-enriched extracellular vesicle (EV) miRNAs as potential biomarkers for anterior circulation LVO (acLVO) stroke. In our longitudinal prospective cohort study, we collected data from acLVO stroke patients at four critical time intervals post-symptom onset: 0–6 h, 6–12 h, 12–24 h, and 5–7 days. For comparative analysis, healthy individuals were included as control subjects. In this study, extracellular vesicles (EVs) were isolated from the plasma of participants, and the miRNAs within these EVs were profiled utilizing the NanoString nCounter system. Complementing this, a scoping review was conducted to examine the roles of specific miRNAs such as miR-140-5p, miR-210-3p, and miR-7-5p in acute ischemic stroke (AIS). This review involved a targeted PubMed search to assess their influence on crucial pathophysiological pathways in AIS, and their potential applications in diagnosis, treatment, and prognosis. The review also included an assessment of additional miRNAs linked to stroke. Within the first 6 h of symptom onset, three specific miRNAs (miR-7-5p, miR-140-5p, and miR-210-3p) exhibited significant differential expression compared to other time points and healthy controls. These miRNAs have previously been associated with neuroprotection, cellular stress responses, and tissue damage, suggesting their potential as early markers of acute ischemic stroke. This study highlights the potential of circulating miRNAs as blood-based biomarkers for hyperacute acLVO ischemic stroke. However, further validation in a larger, risk-matched cohort is required. Additionally, investigations are needed to assess the prognostic relevance of these miRNAs by linking their expression profiles with radiological and functional outcomes. [ABSTRACT FROM AUTHOR]

Analyzing the genetic architecture of hereditary forms of diabetes in different populations is a critical step toward optimizing diagnostic and preventive algorithms. This requires consideration of regional and population-specific characteristics, including the spectrum and frequency of pathogenic variants in targeted genes. As part of this study, we used a custom-designed NGS panel to screen for mutations in 28 genes associated with the pathogenesis of hereditary diabetes mellitus in 506 unrelated patients from Russia. The study identified 180 pathogenic or likely pathogenic variants across 13 genes (GCK, HNF1A, HNF1B, HNF4A, ABCC8, INS, INSR, KCNJ11, PAX4, PDX1, ZFP57, BLK, WFS1), representing 46.44% of the analyzed cohort (235 individuals). The glucokinase gene (GCK) had the highest number of identified variants, with 111 variants detected in 161 patients, 20 of which were identified for the first time. In the tissue-specific transcription factor genes HNF1A, HNF4A, and HNF1B, 34 variants were found in 38 patients, including 13 that were previously unreported. Seventeen variants were identified in the ABCC8 gene, which encodes the ATP-binding cassette transporter 8 of subfamily C, each found in a different patient; four of these were novel discoveries. Nine pathogenic or likely pathogenic variants were identified in the insulin gene (INS) and its receptor gene (INSR), including four previously unreported variants. Additionally, we identified 10 previously unreported variants in six other genes among 11 patients. Variants in the genes GCK, HNF1A, HNF1B, HNF4A, ABCC8, INS, and INSR were the main contributors to the genetic pathogenesis of hereditary diabetes mellitus in the Russian cohort. These findings enhance our understanding of the molecular mechanisms underlying the disease and provide a solid basis for future studies aimed at improving diagnostic accuracy and advancing personalized therapeutic strategies. This knowledge provides a foundation for developing region-specific genetic testing algorithms and personalized therapeutic strategies, which are critical for future initiatives in precision medicine. [ABSTRACT FROM AUTHOR]

Background/Objectives:: The link between serotonergic modulation and depression is under debate; however, serotonin reuptake inhibitors (SRIs) are still the first-choice medicine in this condition. Disturbances in time perception are also reported in depression with one of the behavioral schedules used to study interval timing, differential-reinforcement-learning-of-low-rate, having been shown to have high predictive validity for an antidepressant effect. Here, we introduce an IntelliCage research protocol of an interval bisection task that allows more ecologically valid and less time-consuming rodent examination and provides an example of its use to confirm the previously reported acute effect of an SRI, clomipramine, on interval timing (increase in bisection point, D50). Methods: Wistar male rats (n = 25, five groups of 5–8) were trained in the IntelliCage to discriminate between short (1 s) and long (4 s) LED light stimuli by nose poking at the corresponding (left/right) side of the IntelliCage chamber to obtain a drink. When 80% of correct responses were reached, the intermediate durations of 1.7, 2.5, and 3.3 s were introduced. The number of left/right choices for each stimulus and interval timing parameters (bisection point, D50, and timing precision), derived from them, were compared after saline and clomipramine (7 mg/kg, i.p) intraperitoneal administration. Results: Rats successfully learned the task within about a week of training. The slightly increased D50 after clomipramine confirmed previous studies. Conclusions: The introduced protocol has potential to be applicable to preclinical research on depression and potentially other psychopathology, where time perception can be disturbed. [ABSTRACT FROM AUTHOR]

The summer of 2022 was notable for the Svalbard archipelago due to the occurrence of several longstanding heatwaves, making it one of the warmest summers on the regional record. This study used an energy balance model forced with in situ weather observations to investigate the influence of extreme weather events on the surface energy balance of the low-elevation Aldegondabreen glacier (5.2 km2), located near Barentsburg town, with a focus on the turbulent heat exchange. The annual mass balance for 2022 (−2.13 m w.e.) was one of the most negative on record for Aldegondabreen since 2002/2003 when glaciological monitoring was first initiated. We identified four heatwaves that lasted from 9 to 19 days, the most prominent of which were observed in May and in September–October, which resulted in an anomalously prolonged melt season. In addition, several shorter, 1- to 3-day extreme melt events were identified, representing up to 75 mm w.e. day−1 of glacier-averaged melt. These events were well correlated (r = 0.87, p < 0.01), with discharge from a stream originating from the glacier terminus, and all cases were associated with significant increases in mean daily wind speeds (up to 10.3 m s−1). [ABSTRACT FROM AUTHOR]

The aim of the work was to study the effect of additive concentration on changes in the adhesive and cohesive strength of bitumen. To evaluate the effectiveness of modifiers in the composition of binary and triple bitumen systems in relation to mineral fillers of two grades, the method of determination of the adhesive efficiency and thermodynamic calculations of adhesion and cohesion work were used. The following compounds were used as additives: AS-2 synthesized from the oil refining waste and AG-4I (waste sealing liquid). Adhesion–cohesion processes in modified bitumen systems are limited by the wetting effect of crushed stone and the intensity of intermolecular forces in the condensed phase of the binder. In the binary compositions, the addition of modifiers into bitumen significantly improves the cohesive strength and adhesive efficiency in relation to crushed stone. The introduction of AS-2 into bitumen compositions with AG-4I increases adhesion efficiency and thermodynamic work of adhesion in relation to the filler surface. The adhesion efficiency and thermodynamic work of adhesion in the "bitumen-AG-4I-AS-2" system reach their maximum at CAG-4I = 3.0 g/dm3 and CAS-2 = 1.5 g/dm3. In these concentration modes, the composition ensures maximum increase in adhesion efficiency (AKS = 65.18%; AKA = 48.11%) and the greatest increase in thermodynamic work of adhesion (WA(KS) = 15.79 mN/m; WA(KA) = 14.13 mN/m). [ABSTRACT FROM AUTHOR]

Apurinic/apyrimidinic (AP) sites are endogenous DNA lesions widespread in human cells. Having no nucleobases, they are noncoding and promutagenic. AP site repair is generally initiated through strand incision by AP endonuclease 1 (APE1). Although AP sites' repair in regular B-DNA has been studied extensively, their processing in G-quadruplexes (G4s) has received much less attention. Here, we used the hTERT promoter region that is capable of forming three stacked parallel G4s to understand how AP sites can influence higher-order quadruplex folding and stability and how a G4 affects the efficiency of human APE1-mediated AP site processing. We designed a series of synthetic single- and double-stranded DNA constructs of varying lengths containing a stable AP site analog in both G- and C-rich strands at positions corresponding to somatic driver mutations. Using circular dichroism, we studied the effect of the AP site on hTERT G4 structure and stability. Bio-layer interferometry and gel-based approaches were employed to characterize APE1 binding to the designed DNA substrates and AP site processing. It was shown that (i) an AP site leads to G4 destabilization, which depends on the lesion location in the G4 scaffold; (ii) APE1 binds tightly to hTERT G4 structure but exhibits greatly reduced cleavage activity at AP sites embedded in the quadruplex; and (iii) a clear correlation was revealed between AP site-induced hTERT G4 destabilization and APE1 activity. We can hypothesize that reduced repair of AP sites in the hTERT G4 is one of the reasons for the high mutation rate in this promoter region. [ABSTRACT FROM AUTHOR]

A comparative metabolomic study of three varieties of wild Rosa (Rosa acicularis, Rosa amblyotis, and Rosa rugosa) from a Kamchatka expedition (2024) was conducted via extraction with supercritical carbon dioxide modified with ethanol (EtOH), and detection of bioactive compounds was realized via tandem mass spectrometry. Several experimental conditions were investigated in the pressure range 50–350 bar, with the used volume of co-solvent ethanol in the amount of 2% in the liquid phase at a temperature in the range of 31–70 °C. The most effective extraction conditions are the following: pressure 200 Bar and temperature 55 °C for Rosa acicularis; pressure 250 Bar and temperature 60 °C for Rosa amblyotis; pressure 200 Bar and temperature 60 °C for Rosa rugosa. Three varieties of wild Rosa contain various phenolic compounds and compounds of other chemical groups with valuable biological activity. Tandem mass spectrometry (HPLC-ESI–ion trap) was applied to detect the target analytes. A total of 283 bioactive compounds (two hundred seventeen compounds from the polyphenol group and sixty-six compounds from other chemical groups) were tentatively identified in extracts from berries of wild Rosa. For the first time, forty-eight chemical constituents from the polyphenol group (15 flavones, 14 flavonols, 4 flavan-3-ols, 3 flavanones, 1 phenylpropanoid, 2 gallotannins, 1 ellagitannin, 4 phenolic acids, 1 dihydrochalcone, and 3 coumarins) were identified in supercritical extracts of R. acicularis, R. amblyotis, and R. rugosa. [ABSTRACT FROM AUTHOR]

Objective: We evaluate the immunotherapeutic potential of the yellow fever virus vaccine strain 17D (YFV 17D) for intratumoral therapy of pancreatic cancer in mice. Methods: The cytopathic effect of YFV 17D on mouse syngeneic pancreatic cancers cells were studied both in vitro and in vivo and on human pancreatic cancers cells in vitro. Results: YFV 17D demonstrated a strong cytopathic effect against human cancer cells in vitro. Although YFV 17D did not exhibit a lytic effect against Pan02 mouse cells in vitro, a single intratumoral administration of 17D caused a delay in tumor growth and an increase in median survival by 30%. Multiple injections of 17D did not further improve the effect on tumor growth; however, it notably extended the median survival. Furthermore, preliminary immunization with 17D enhanced its oncotherapeutic effect. Conclusions: Intratumoral administration of yellow fever virus vaccine strain 17D delayed tumor in a murine model of pancreatic cancer. The fact that YFV 17D in vitro affected human cancer cells much more strongly than mouse cancer cells appears promising. Hence, we anticipate that the in vivo efficacy of YFV-17D-based oncolytic therapy will also be higher against human pancreatic carcinomas compared to its effect on the mouse pancreatic tumor. [ABSTRACT FROM AUTHOR]

Background/Objectives: Intranasal vaccination enhances protection against respiratory viruses by providing stimuli to the immune system at the primary site of infection, promoting a balanced and effective response. Influenza vectors with truncated NS1 are a promising vaccine approach that ensures a pronounced local CD8+ T-cellular immune response. Here, we describe the protective and immunomodulating properties of an influenza vector FluVec-N carrying the C-terminal fragment of the SARS-CoV-2 nucleoprotein within a truncated NS1 open reading frame. Methods: We generated several FluVec-N recombinant vectors by reverse genetics and confirmed the vector's genetic stability, antigen expression in vitro, attenuation, and immunogenicity in a mouse model. We tested the protective potential of FluVec-N intranasal immunization in naïve mice and seropositive Th2-prone mice, primed with aluminium-adjuvanted inactivated SARS-CoV-2. Immune response in immunized and challenged mice was analyzed through serological methods and flow cytometry. Results: Double intranasal immunization of naïve mice with FluVec-N reduced weight loss and viral load in the lungs following infection with the SARS-CoV-2 beta variant. Mice primed with alum-adjuvanted inactivated coronavirus experienced substantial early weight loss and eosinophilia in the lungs during infection, demonstrating signs of enhanced disease. A single intranasal boost immunization with FluVec-N prevented the disease enhancement in primed mice by modulating the local immune response. Protection was associated with the formation of specific IgA and the early activation of virus-specific effector and resident CD8+ lymphocytes in mouse lungs. Conclusions: Our study supports the potential of immunization with influenza vector vaccines to prevent respiratory diseases and associated immunopathology. [ABSTRACT FROM AUTHOR]

Human Immunodeficiency Virus (HIV) proviral reservoirs are cells that harbor integrated HIV proviral DNA within their nuclear genomes. These cells form a heterogeneous group, represented by peripheral blood mononuclear cells (PBMCs), tissue-resident lymphoid and monocytic cells, and glial cells of the central nervous system. The importance of studying the properties of proviral reservoirs is connected with the inaccessibility of integrated HIV proviral DNA for modern anti-retroviral therapies (ARTs) that block virus reproduction. If treatment is not effective enough or is interrupted, the proviral reservoir can reactivate. Early initiation of ART improves the prognosis of the course of HIV infection, which is explained by the reduction in the proviral reservoir pool observed in the early stages of the disease. Different HIV subtypes present differences in the number of latent reservoirs, as determined by structural and functional differences. Unique signatures of patients with HIV, such as elite controllers, have control over viral replication and can be said to have achieved a functional cure for HIV infection. Uncovering the causes of this phenomenon will bring humanity closer to curing HIV infection, potential approaches to which include stem cell transplantation, clustered regularly interspaced short palindromic repeats (CRISPR)/cas9, "Shock and kill", "Block and lock", and the application of broad-spectrum neutralizing antibodies (bNAbs). [ABSTRACT FROM AUTHOR]

Sunflower (Helianthus annuus L.) is specifically infected by an obligatory root parasitic plant Orobanche cumana Wallr. (sunflower broomrape), which causes significant losses of sunflower yield. Breeding of sunflower varieties resistant to broomrape is an important challenge for agriculture. However, the selection of new resistant sunflower varieties was accompanied by the emergence of new virulent races of broomrape, which overcame the effect of resistance genes. Unraveling the molecular mechanisms underlying the resistance to broomrape in sunflowers should facilitate the development of new sunflower varieties with complex resistance to broomrape using genome editing technology. Here, we used CRISPR/Cas9-mediated genome editing in sunflower hairy roots for a specific knock-out of the gene encoding a GRAS transcription factor (HaNSP1a), acting as a possible regulator of strigolactone biosynthesis, a class of phytohormones known to induce the germination of broomrape seeds. According to HPLC-IT-TOF/MS analysis, the levels of orobanchol were decreased in the genetically modified roots with knock-out of the HaNSP1a gene, whereas, in contrast, 5-deoxystrigol levels were increased in the roots with HaNSP1a knock-out, suggesting the role of HaNSP1a in the regulation of the strigolactone biosynthetic pathway. The experimental approach described here could be used in further studies to test the effect of gene knock-out on the development of resistance to O. cumana in sunflowers. [ABSTRACT FROM AUTHOR]

The increasing demand for sustainable energy has spurred interest in biofuels as a renewable alternative to fossil fuels. Biomass gasification and pyrolysis are two prominent thermochemical conversion processes for biofuel production. While these processes are effective, they are often influenced by complex, nonlinear, and uncertain factors, making optimization and prediction challenging. This study highlights the application of fuzzy neural networks (FNNs)—a hybrid approach that integrates the strengths of fuzzy logic and neural networks—as a novel tool to address these challenges. Unlike traditional optimization methods, FNNs offer enhanced adaptability and accuracy in modeling nonlinear systems, making them uniquely suited for biomass conversion processes. This review not only highlights the ability of FNNs to optimize and predict the performance of gasification and pyrolysis processes but also identifies their role in advancing decision-making frameworks. Key challenges, benefits, and future research opportunities are also explored, showcasing the transformative potential of FNNs in biofuel production. [ABSTRACT FROM AUTHOR]

Glioblastoma is one of the most aggressive brain cancers, characterized by active infiltrative growth and high resistance to radiotherapy and chemotherapy. Sesquiterpene triterpenoids (STLs) and their semi-synthetic analogs are considered as a promising source of novel anti-tumor agents due to their low systemic toxicity and multi-target pharmacological effects on key processes associated with tumor progression. The current review aims to systematize the knowledge on the anti-glioblastoma potential of STLs accumulated over the last decade and to identify key processes in glioblastoma cells that are most susceptible to the action of STLs. An analysis of published data clearly demonstrated that STLs, which can successfully cross the blood–brain barrier, exert a complex inhibitory effect on glioblastoma cells through the induction of the "mitochondrial dysfunction–oxidative stress–apoptosis" axis, the inhibition of glucose metabolism and cell cycle phase transition, and the suppression of glioblastoma cell motility and invasion through the blockade of proneural–mesenchymal transition. Taken together, this review highlights the promising anti-glioblastoma potential of STLs, which are not only able to induce glioblastoma cell death, but also effectively affect their diffusive spread, and suggests the possible directions for further investigation of STLs in the context of glioblastoma to better understand their mechanism of action. [ABSTRACT FROM AUTHOR]

This paper proposes and implements a novel scheme for recording signals from fibre optic sensors based on tandem low-coherence interferometry with an integrated optical reference interferometer. The circuit allows precision control of the phase shift. Additionally, the paper illustrates the potential for detecting vibration and object deformation using fibre optic Fabry–Perot sensors connected to the registration system. [ABSTRACT FROM AUTHOR]

Previously we discovered that among 15 DNA-binding plant secondary metabolites (PSMs) possessing anticancer activity, 11 compounds cause depletion of the chromatin-bound linker histones H1.2 and/or H1.4. Chromatin remodeling or multiH1 knocking-down is known to promote the upregulation of repetitive elements, ultimately triggering an interferon (IFN) response. Herein, using HeLa cells and applying fluorescent reporter assay with flow cytometry, immunofluorescence staining and quantitative RT-PCR, we studied effects of PSMs both evicting linker histones from chromatin and not influencing their location in nucleus. We found that (1) 8 PSMs, evicting linker histone H1.2 from chromatin, activated significantly the type I IFN signaling pathway and out of these compounds resveratrol, berberine, genistein, delphinidin, naringenin and curcumin also caused LINE1 expression. Fisetin and quercetin, which also induced linker histone H1.2 eviction from chromatin, significantly activated only type I IFN signaling, but not LINE1 expression; (2) curcumin, sanguinarine and kaempferol, causing significant depletion of the chromatin-bound linker histone H1.4 but not significantly influencing H1.2 presence in chromatin, activate type I IFN signaling less intensively without any changes in LINE1 expression; (3) four PSMs, which did not cause linker histone eviction, displayed neither IFN signaling activation nor enhancement of LINE1 expression. Thus, we have shown for the first time that chromatin destabilization observed by depletion of chromatin-bound linker histone H1.2 caused by anticancer DNA-binding PSMs is accompanied by enhancement of type I IFN signaling, and that LINE1 expression often impacts this activation. [ABSTRACT FROM AUTHOR]

Glucocorticoids (GCs) are routinely used to treat hematological malignancies; however, long-term treatment with GCs can lead to atrophic and metabolic adverse effects. Selective glucocorticoid receptor agonists (SEGRAs) with reduced side effects may act as a superior alternative to GCs. More than 30 SEGRAs have been described so far, yet none of them reached clinical trials for anti-cancer treatment. In the present work, we propose a novel approach to increase the number of potential SEGRAs by obtaining derivatives of synephrine, a molecule of natural origin. We synthesized 26 novel compounds from the class of synephrine derivatives and characterized them by HRMS, and 1H and 13C NMR. We evaluated in vitro anti-cancer effects in leukemia K562 and lymphoma Granta cells using the MTT assay and studied their potential affinity for the glucocorticoid receptor (GR) in silico using the molecular docking approach. The novel derivative 1-[4-(benzyloxy)phenyl]-2-(hexylamino)ethanol (10S-E2) with the highest GR affinity in silico exhibited cytotoxic activity against K562 and Granta cells after 24 h of treatment at the concentration of approximately 13 µM which correlated with its highest MolDock Score. The other compound with high GR affinity, 2-(hexylamino)-1-(4-nitrophenyl)ethanol (13S-G2), demonstrated cytotoxicity in both cell lines at concentrations of 50–70 µM. Overall, our results may provide a solid rationale for developing and further investigating synephrine derivatives as SEGRAs with anti-cancer activity. [ABSTRACT FROM AUTHOR]

The effective use of polymer carbon dots (PCD) in various fields of science and technology requires a more detailed understanding of the mechanisms of their photoluminescence formation and change as a result of their interaction with the environment. In this study, PCD synthesized via a hydrothermal method from citric acid and ethylenediamine are studied in various solvents using FTIR spectroscopy, optical absorption spectroscopy, and photoluminescence spectroscopy. As a result of the analysis of the obtained dependencies of such PCD spectral characteristics as the photoluminescence FWHM, the photoluminescence quantum yield, the photoluminescence lifetime on the acidity and basicity of the solvent, a hypothesis was formulated on the formation mechanism of hydrogen bonds between the PCD surface groups and the molecules of the environment, and conclusions were made about the donor–acceptor nature of the synthesized PCD. [ABSTRACT FROM AUTHOR]

With the increasing need to tackle climate change, energy efficiency and reduced CO2 emissions are proving to be one of society's greatest challenges. Special consideration should be given to heating systems as they are prone to inefficiency due to non-optimal controller configurations and the shortage of experts or qualified technicians to optimize the operating behavior. Especially for residential heating systems, more often than not, the target metric is the achievement of specific heating and hot water temperatures by manual adjustments with limited sensor information and with little regard to efficiency. This presents potential for computer-aided optimization based on artificial intelligence techniques. In this paper, we presented a Decision Integration System that is interfaced with a data acquisition infrastructure and allows for the analysis of measured heating system data, the generation of recommended measures for efficiency improvement, and the simulative validation of recommended controller parameter changes. We presented different parts of the Decision Integration System, the interfaced data acquisition infrastructure, as well as the non-invasive sensor appliances used. We analyzed the measured data of real heating systems and evaluated our approach by generating the recommended measures based on rules created by heating system experts, which were then partially applied to the physical heating systems and partially evaluated in simulation. Finally, we compared long-term energy consumption data against the latest monitoring period after implementing the measures. Our results showed an average reduction in energy consumption of 24.52% across all considered buildings, corresponding to an approximate reduction of 8.12 tons of CO2 emissions. [ABSTRACT FROM AUTHOR]

Plant genomes possess numerous transposable element (TE) insertions that have occurred during evolution. Most TEs are silenced or diverged; therefore, they lose their ability to encode proteins and are transposed in the genome. Knowledge of active plant TEs and TE-encoded proteins essential for transposition and evasion of plant cell transposon silencing mechanisms remains limited. This study investigated active long terminal repeat (LTR) retrotransposons (RTEs) in sunflowers (Helianthus annuus), revealing heterogeneous and phylogenetically distinct RTEs triggered by epigenetic changes and heat stress. Many of these RTEs belong to three distinct groups within the Tekay clade, showing significant variations in chromosomal insertion distribution. Through protein analysis of these active RTEs, it was found that Athila RTEs and Tekay group 2 elements possess additional open reading frames (aORFs). The aORF-encoded proteins feature a transposase domain, a transmembrane domain, and nuclear localization signals. The aORF proteins of the Tekay subgroup exhibited remarkable conservation among over 500 Tekay members, suggesting their functional importance in RTE mobility. The predicted 3D structure of the sunflower Tekay aORF protein showed significant homology with Tekay proteins in rice, maize, and sorghum. Additionally, the structural features of aORF proteins resemble those of plant DRBM-containing proteins, suggesting their potential role in RNA-silencing modulation. These findings offer insights into the diversity and activity of sunflower RTEs, emphasizing the conservation and structural characteristics of aORF-encoded proteins. [ABSTRACT FROM AUTHOR]

Time perception is a fundamental cognitive function essential for adaptive behavior and shared across species. The neural mechanisms underlying time perception, particularly its neuromodulation, remain debated. In this review, we examined the role of the serotonergic system in time perception (at the scale of seconds and minutes), building a translational bridge between human and non-human animal studies. The literature search was conducted according to the PRISMA statement in PubMed, APA PsycINFO, and APA PsycARTICLES. Sixty papers were selected for full-text review, encompassing both human (n = 10) and animal studies (n = 50). Summarizing the reviewed literature, we revealed consistent evidence for the role of serotonin in timing behavior, highlighting its complex involvement across retrospective, immediate, and prospective timing paradigms. Increased serotonergic activation appears to accelerate internal time speed, which we interpret through the dual klepsydra model as accelerated discharge of the temporal accumulator. However, some findings challenge this framework. Additionally, we link impulsivity—associated with decreased serotonergic functioning in our review—to a slower internal time speed. Variability in prospective timing tasks underscores the need for further research into how serotonin modulates reward-based temporal decisions, using novel approaches to disentangle internal time speed, response inhibition, and other factors. [ABSTRACT FROM AUTHOR]

This article compares the properties of the diamond-like carbon (DLC) coating with those of ZrN and (Zr,Hf)N coatings deposited on the Ti-6Al-4V titanium alloy substrate. To improve substrate adhesion during the deposition of the DLC coating, preliminary etching with chromium ions was conducted, ensuring the formation of a chromium-saturated diffusion surface layer in the substrate. A Si-DLC layer followed by a pure DLC layer was then deposited. The hardness of the coatings, their surface morphology, fracture strength in the scratch test, and tribological properties and wear resistance in the pin-on-disk test in contact with Al2O3 and steel indenters were investigated. The structure of the DLC coating was studied using transmission electron microscopy, and its corrosion resistance in an environment simulating blood plasma was also investigated. In the pin-on-disk test in contact with Al2O3 and AISI 52100 indenters, the DLC-coated sample demonstrates a much lower friction coefficient and significantly better wear resistance compared to the nitride-coated and uncoated samples. Both nitride coatings—(Zr,Hf)N and ZrN—and the DLC coating slow down the corrosive dissolution of the base compared to the uncoated sample. The corrosion currents of the (Zr,Hf)N-coated samples are 37.01 nA/cm2, 20% higher than those of the ZrN-coated samples. The application of (Zr,Hf)N, ZrN, and DLC coatings on the Ti-6Al-4V alloy significantly inhibits dissolution currents (by 30–40%) and increases polarization resistance 1.5–2.0-fold compared to the uncoated alloy in 0.9% NaCl at 40 °C. Thus, the DLC coating of the described structure simultaneously provides effective wear and corrosion resistance in an environment simulating blood plasma. This coating can be considered in the manufacture of medical products (in particular, implants) from titanium alloys, including those functioning in the human body and subject to mechanical wear (e.g., knee joint endoprostheses). [ABSTRACT FROM AUTHOR]

Background/Objectives: Influenza viruses and SARS-CoV-2 are currently cocirculating with similar seasonality, and both pathogens are characterized by a high mutational rate which results in reduced vaccine effectiveness and thus requires regular updating of vaccine compositions. Vaccine formulations combining seasonal influenza and SARS-CoV-2 strains can be considered promising and cost-effective tools for protection against both infections. Methods: We used a licensed seasonal trivalent live attenuated influenza vaccine (3×LAIV) as a basis for the development of a modified 3×LAIV/CoV-2 vaccine, where H1N1 and H3N2 LAIV strains encoded an immunogenic cassette enriched with conserved T-cell epitopes of SARS-CoV-2, whereas a B/Victoria lineage LAIV strain was unmodified. The trivalent LAIV/CoV-2 composition was compared to the classical 3×LAIV in the golden Syrian hamster model. Animals were intranasally immunized with the mixtures of the vaccine viruses, twice, with a 3-week interval. Immunogenicity was assessed on day 42 of the study, and the protective effect was established by infecting vaccinated hamsters with either influenza H1N1, H3N2 or B viruses or with SARS-CoV-2 strains of the Wuhan, Delta and Omicron lineages. Results: Both the classical 3×LAIV and 3×LAIV/CoV-2 vaccine compositions induced similar levels of serum antibodies specific to all three influenza strains, which resulted in comparable levels of protection against challenge from either influenza strain. Protection against SARS-CoV-2 challenge was more pronounced in the 3×LAIV/CoV-2-immunized hamsters compared to the classical 3×LAIV group. These data were accompanied by the higher magnitude of virus-specific cellular responses detected by ELISPOT in the modified trivalent LAIV group. Conclusions: The modified trivalent live attenuated influenza vaccine encoding the T-cell epitopes of SARS-CoV-2 can be considered a promising tool for combined protection against seasonal influenza and COVID-19. [ABSTRACT FROM AUTHOR]

Geographic patterns determine geogenic radon factors that, changing over the territory, form spatial structures of different scales associated with regional and local variations. The study of these structures is important for assessing the possibility of using limited data to predict geogenic radon potential. Our research focuses on the study of the physical properties of soils (moisture, soil density, porosity and void ratio) in the Kuznetsk coal basin. Their variations are studied using statistical methods, a variogram cloud and spatial autocorrelation of data. Soil moisture and porosity have the greatest variability in space and with depth. We conclude that the assessment of geogenic radon predictors requires consideration of the variation coefficient and autocorrelation indices at different scales. Based on the variability of humidity and the fairly homogeneous nature of the studied soils (loams), to assess the radon hazard, it is necessary to study the influence of climatic conditions, since the permeability of the environment for radon will be determined by soil moisture. With the predominance of substantially clayey soils, it is necessary to study the content of 226Ra in the upper horizons, since it is assumed that radon is predominantly diffusely transferred, in which its role is dominant. [ABSTRACT FROM AUTHOR]

Novel multicomponent Nb–Ni–Ti–Zr–Co alloys with 20–55 at.% Nb were synthesized from metal powders by arc melting. The resulting alloys consist primarily of Nb-rich and eutectic body-centered (BCC) phases. The content of the eutectic BCC phase is highest for an equimolar composition, while the content of the Nb-rich BCC phase increases with Nb content in the alloy. The content of secondary phases is the highest for the alloy with 32 at.% Nb. According to ab initio calculations, hydrogen occupies tetrahedral interstitial sites in the Nb-rich phase and octahedral sites in the eutectic BCC phase. For different Nb concentrations, hydrogen-binding energies were calculated. An increase in the Nb-rich phase leads to softening of multicomponent alloys. The alloys with 20 and 32 at.% Nb demonstrate high hydrogen permeability (1.05 and 0.96 × 10−8 molH2m−1s−1Pa−0.5, respectively) at 400 °C, making them promising for hydrogen purification membrane application. Multicomponent alloys with a high Nb content (55 at.%) have low resistance to hydrogen embrittlement. [ABSTRACT FROM AUTHOR]

Metabolomics investigates final and intermediate metabolic products in cells. Assessment of the human metabolome relies principally on the analysis of blood, urine, saliva, sweat, and feces. Tissue biopsy is employed less frequently. Understanding the metabolite composition of biosamples from athletes can significantly improve our knowledge of molecular processes associated with the efficiency of training and recovery. Such knowledge may also lead to new management opportunities. Successful execution of metabolomic studies requires simultaneous qualitative and quantitative analyses of numerous small biomolecules in samples under test. Unlike genomics and proteomics, which do not allow for direct assessment of enzymatic activity, metabolomics focuses on biochemical phenotypes, providing unique information about health and physiological features. Crucial factors in ensuring the efficacy of metabolomic analysis are the meticulous selection and pre-treatment of samples. [ABSTRACT FROM AUTHOR]

Simple Summary: Air pollution has been identified as a contributing factor to increasing antibiotic-resistant bacteria in the microbiome of dust particles. The aim of the study was to structurally and functionally characterise the microbial communities of dust particles in urban ecosystems of Moscow and to compare the prevalence of predicted resistome modules and culturable antibiotic-resistant bacteria in the microbiomes. The present study revealed a higher prevalence of antibiotic-resistant bacteria in the microbiomes of dust particles sampled in the most polluted functional zones of Moscow. Furthermore, antibiotic resistance was a more diverse functional characteristic of the microbial communities of airborne particles. Urban dust samples were collected in Moscow (Russia) in June 2021. The samples were collected in three functional zones of Moscow (traffic, residential, and recreational) and included air microparticles, leaf dust, and paved dust. Data on the taxonomic composition of bacterial communities were obtained for dust samples, and their functional characteristics were predicted using PICRUSt2 2.5.0 and FAPROTAX 1.8.0 software. The culturable part of the bacterial community was examined for the presence of antibiotic-resistant strains with respect to β-lactams, tetracyclines, amphenicols, and aminoglycosides. The presence of bacteria resistant to ceftazidime, cefepime, and tetracycline was detected in all dust samples. The presence of bacteria resistant to meropenem and amikacin was only observed in the dust collected from leaves in the residential and traffic zones. The overall abundance of cultured antibiotic-resistant bacteria from the total heterotrophs ranged from 0.03% to 1.88%, with the highest percentage observed in dust from the residential zone. Notably, strains resistant to all antibiotics tested were observed in the leaf dust bacterial community. [ABSTRACT FROM AUTHOR]

The dispersal of plant pathogens is a threat to the global economy and food industry which necessitates the need to discover efficient biocontrol agents such as bacteria, fungi, etc., inhibiting them. Here, we describe the Bacillus mycoides strain b12.3 isolated from the soil of Olkhon Island in Lake Baikal, Russia. By applying the co-cultivation technique, we found that the strain inhibits the growth of plant pathogens, such as the bacteria Xanthomonas campestris, Clavibacter michiganensis, and Pectobacterium atrospecticum, as well as the fungus Alternaria solani. To elucidate the genomic fundament explaining these activities, we leveraged next-generation whole-genome sequencing and obtained a high-quality assembly based on short reads. The isolate bore seven known BGCs (biosynthetic gene clusters), including those responsible for producing bacillibactin, fengycin, and petrobactin. Moreover, the genome contained insecticidal genes encoding for App4Aa1, Tpp78Ba1, and Spp1Aa1 toxins, thus implicating possible pesticidal potential. We compared the genome with the 50 closest assemblies and found that b12.3 is enriched with BGCs. The genomic analysis also revealed that genomic architecture corresponds to the experimentally observed activity spectrum implying that the combination of produced secondary metabolites delineates the range of inhibited phytopathogens Therefore, this study deepens our knowledge of the biology and ecology of B. mycoides residing in the Lake Baikal region. [ABSTRACT FROM AUTHOR]

Pesticide-free agriculture is a fundamental pillar of environmentally friendly agriculture. To this end, there is an active search for new bacterial strains capable of synthesizing secondary metabolites and toxins that protect crops from pathogens and pests. In this study, we isolated a novel strain d21.2 of Peribacillus frigoritolerans from a soil sample collected in the Republic of Dagestan, Russia. Leveraging several bioinformatic approaches on Illumina-based whole-genome assembly, we revealed that the strain harbors certain insecticidal loci (coding for putative homologs of Bmp and Vpa) and also contains multiple BGCs (biosynthetic gene clusters), including paeninodin, koranimine, schizokinen, and fengycin. In total, 21 BGCs were predicted as synthesizing metabolites with bactericidal and/or fungicidal effects. Importantly, by applying a re-scaffolding pipeline, we managed to robustly predict MGEs (mobile genetic elements) associated with BGCs, implying high genetic plasticity. In addition, the d21.2's genome was free from genes encoding for enteric toxins, implying its safety in use. A comparison with available genomes of the Peribacillus frigoritolerans strain revealed that the strain described here contains more functionally important loci than other members of the species. Therefore, strain d21.2 holds potential for use in agriculture due to the probable manifestation of bactericidal, fungicidal, growth-stimulating, and other useful properties. The assembled genome is available in the NCBI GeneBank under ASM4106054v1. [ABSTRACT FROM AUTHOR]

The study specifies the changes in radon activity concentration (RAC) in soil gas with depth and emphasizes the significance of the meteorological factor for deeper boreholes. Radon activity concentration was measured in 0.6 m, 1 m and 1.5 m boreholes, and the depth gradient was also calculated. Spatial patterns were estimated using an autocorrelation index. RAC ranged from 9454 ± 439 Bq/m3 for 0.6 m, 16,031 ± 602 Bq/m3 for 1 m and 22,049 ± 937 Bq/m3 for 1.5 m. RAC increased with depth at most of the study sites and behaved quite uniformly in spatial terms. At the same time, no significant differences in the activity of uranium (238U) series isotopes at different soil depths were detected. Significant spatial variability in radioactivity and the physical properties of soils is noted. The highest gradient was between 0.6 and 1 m. It was found that with increasing depth the connection between the RAC and the meteorological conditions (temperature and humidity) of the surface layer of the atmosphere is lost. It follows that for shallow boreholes it is necessary to consider the influence of meteorological conditions. RAC in 1 m boreholes correlates with 1.5 m and 0.6 m boreholes, but no correlation was found for the 1.5 m and 0.6 m boreholes themselves. Thus, 1 m boreholes are optimal for radon monitoring. A high level of RAC indicates a high potential for indoor radon exposure in this territory, with corresponding epidemiological consequences in the long term. [ABSTRACT FROM AUTHOR]

As a promising polymer for the production of biomaterials and drug delivery systems, poly(lactic acid) (PLA) is characterized by its relative hydrophobicity, as well as its chemical and biological inertness. Here, we aimed to improve the biological properties of PLA-based materials via the covalent attachment of a hydrophilic biocompatible glycopolymer, namely poly(2-deoxy-N-methacrylamido-D-glucose) (PMAG) on their surface. PMAG is a water-soluble polymer that contains glucose units in its side chains, which are responsible for good biocompatibility and the ability to attach bioactive molecules. In the developed protocol, PMAG was synthesized by controlled radical polymerization in the presence of a reversible addition–fragmentation chain transfer (RAFT) agent, followed by the conversion of glycopolymer terminal dithiobenzoate functionality into a primary amino group (PMAG-NH2). PLA-based films served as model aliphatic polyester materials for developing the surface biofunctionalization protocol. According to that, PMAG-NH2 covalent immobilization was carried out after alkali treatment, allowing the generation of the surface-located carboxyl groups and their activation. The developed modification method provided a one-point attachment of hydrophilic PMAG to the hydrophobic PLA surface. PMAG samples, which differed by the degree of polymerization, and the variation of polymer concentration in the reaction medium were applied to investigate the modification efficacy and grafting density. The developed single-point polymer grafting approach provided the efficient functionalization with a grafting density in the range of 5–23 nmol/cm2. The neat and modified polymer films were characterized by a number of methods, namely atomic force microscopy, thermogravimetric analysis, ellipsometry, and contact angle measurements. In addition, an ArgGlyAsp-containing peptide (RGD peptide) was conjugated to the PMAG macromolecules grafted on the surface of PLA films. It was shown that both surface modification with PMAG and with PMAG-RGD peptide enhanced the adhesion and growth of mesenchymal stem cells as compared to a neat PLA surface. [ABSTRACT FROM AUTHOR]

Background: Undifferentiated pleomorphic sarcoma (UPS) is a highly malignant mesenchymal tumor that ranks as one of the most common types of soft tissue sarcoma. Even though chemotherapy increases the 5-year survival rate in UPS, high tumor heterogeneity frequently leads to chemotherapy resistance and consequently to recurrences. In this study, we characterized the cell composition and the transcriptional profile of UPS with resistance to chemotherapy at the single cell resolution. Methods: A 58-year-old woman was diagnosed with a 13.6 × 9.3 × 6.0 cm multi-nodular tumor with heterogeneous cysto-solid structure at the level of the distal metadiaphysis of the left thigh during magnetic resonance tomography. Morphological and immunohistochemical analysis led to the diagnosis of high-grade (G3) UPS. Neoadjuvant chemotherapy, surgery (negative resection margins), and adjuvant chemotherapy were conducted, but tumor recurrence developed. The UPS sample was used to perform single-cell RNA sequencing by chromium-fixed RNA profiling. Results: Four subpopulations of tumor cells and seven subpopulations of tumor microenvironment (TME) have been identified in UPS. The expression of chemoresistance genes has been detected, including KLF4 (doxorubicin and ifosfamide), ULK1, LUM, GPNMB, and CAVIN1 (doxorubicin), and AHNAK2 (gemcitabine) in tumor cells and ETS1 (gemcitabine) in TME. Conclusions: This study provides the first description of the single-cell transcriptome of UPS with resistance to two lines of chemotherapy, showcasing the gene expression in subpopulations of tumor cells and TME, which may be potential markers for personalized cancer therapy. [ABSTRACT FROM AUTHOR]

The leaching kinetics of an industrial iron collector containing PGMs (Pd, Pt, Rh) in HCl and HF solutions were investigated. The effects of the HCl concentration (2.74–6.86 mol/L), the HF concentration (1.46–7.50 mol/L), temperature (323–363 K), and leaching time (0–210 min) on the extraction of Fe into the solution and Si into the gas phase from the iron collector were studied. The HCl concentration had a negative effect on the extraction of Si, which decreased from 78.2% to 58.1% and from 97.4% to 87.2% in the time ranges of 0–30 min and 30–120 min, respectively. This occurred due to the accumulation of Fe2+ in the solution and its interaction with HF, which led to a reduction in both the HF concentration and the extraction of Si. In addition, there were diffusion difficulties of the Fe and Si extraction because Fe precipitated on the surface of the cakes in the form of thin-film conglomerates of FeF2. This was confirmed by the XRF and EDS results, indicating that F was present on the surface of the cakes. The processes of the Fe and Si extraction were diffusion-chemically controlled and diffusion controlled—the apparent activation energies decreased from 26.9 kJ/mol to 7.8 kJ/mol and from 2.2 kJ/mol to 2.0 kJ/mol in the time range of 0–120 min, respectively. Using the shrinking core model and the full factorial experiment model, the kinetic equations, the optimal parameters of iron collector leaching, and the extraction rates of Fe and Si were determined. These optimal parameters ensure the extraction of Fe and Si at the level of 95% with high leaching rates: the HCl concentration of 4.36 mol/L, the HF concentration of 6.93 mol/L, temperature of 363 K, and leaching time of 80 min. [ABSTRACT FROM AUTHOR]

In the emerging field of computational gastronomy, aligning culinary practices with scientifically supported nutritional goals is increasingly important. This study explores how large language models (LLMs) can be applied to optimize ingredient substitutions in recipes, specifically to enhance the phytochemical content of meals. Phytochemicals are bioactive compounds found in plants, which, based on preclinical studies, may offer potential health benefits. We fine-tuned models, including OpenAI's GPT-3.5-Turbo, DaVinci-002, and Meta's TinyLlama-1.1B, using an ingredient substitution dataset. These models were used to predict substitutions that enhance the phytochemical content and to create a corresponding enriched recipe dataset. Our approach improved the top ingredient prediction accuracy on substitution tasks, from the baseline 34.53 ± 0.10% to 38.03 ± 0.28% on the original substitution dataset and from 40.24 ± 0.36% to 54.46 ± 0.29% on a refined version of the same dataset. These substitutions led to the creation of 1951 phytochemically enriched ingredient pairings and 1639 unique recipes. While this approach demonstrates potential in optimizing ingredient substitutions, caution must be taken when drawing conclusions about health benefits, as the claims are based on preclinical evidence. This research represents a step forward in using AI to promote healthier eating practices, providing potential pathways for integrating computational methods with nutritional science. [ABSTRACT FROM AUTHOR]

Macular atrophy (MA) is an irreversible endpoint of age-related macular degeneration (AMD), which is the leading cause of blindness in the world. Early detection is therefore an unmet need. We have developed a novel automated method to identify MA in patients undergoing follow-up with optical coherence tomography (OCT) for AMD based on the combination of 2D and 3D Unet architecture. Our automated detection of MA relies on specific structural changes in OCT, including six established atrophy-associated lesions. Using 1241 volumetric OCTs from 125 eyes (89 patients), the performance of this combination Unet architecture is extremely encouraging, with a mean dice similarity coefficient score of 0.90 ± 0.14 and a mean F1 score of 0.89 ± 0.14. These promising results have indicated superiority when compared to human graders, with a mean similarity of 0.71 ± 0.27. We believe this deep learning-aided tool would be useful to monitor patients with AMD, enabling the early detection of MA and supporting clinical decisions. [ABSTRACT FROM AUTHOR]

In this work, the optical parameters of a 550 μm thick deuterated triglycine sulfate (DTGS) crystal in the range of 0.3–1.5 THz were investigated in low and high fields by time-domain spectroscopy. The X and Z axes of the refractive index ellipsoid were identified, and the refractive indices and extinction coefficients were determined. In addition, it was shown that, in strong THz fields, a phonon A-mode with a frequency of about 40 cm−1 can be excited in the DTGS crystal when the THz wave vector coincides with the polar axis of the crystal and the polarization of the THz radiation coincides with the X-axis of the crystal. The use of the observed effect and the determination of the mode excitation parameters can be twofold. First, they show the limits of the THz field for non-invasive action on the crystal. Second, they present the mode excitation conditions that can be used, for example, in controllable absorbers. [ABSTRACT FROM AUTHOR]

The effect of the Mn3+ ion on the local distortions of FeO6 octahedra in orthoferrite samples was investigated. Mössbauer spectroscopy measurements for a series of HoFe 1 − x Mn x O 3 (x = 0–0.7) orthoferrite samples with the space group Pnma were carried out at temperatures above the Néel point (700 K). The electric field gradient (EFG) tensor on Fe ions for these compounds was found using first-principle calculations. The concentration dependence of quadrupole splitting was obtained using experimental and theoretical data. Mn3+ cations were found to affect the Mössbauer spectra mainly due to distortions of the crystal lattice. Theoretical calculations show that the values of all electric field gradient components increase significantly with the manganese concentration in the system, and the eigenvectors e xx and e yy of the electric field gradient tensor sharply change their direction at concentrations of x > 0.1. [ABSTRACT FROM AUTHOR]

Simple Summary: This research focuses on finding more efficient and cost-effective methods for the development of therapeutic agents to treat malignant tumors. The study explores the design of special molecules called aptamers, which can bind to cancer cells and help in diagnosis and treatment. However, creating these molecules can be expensive and technically challenging. Using computer modeling, a way was found to simplify these molecules, reducing unnecessary parts while keeping their effectiveness intact. This method not only cuts down on production costs but also improves how quickly and precisely these molecules can work within the body. This approach promises to benefit researchers in developing targeted cancer therapies, even when detailed information about the cancer targets is lacking. Background: Oncological diseases are a major focus in medicine, with millions diagnosed each year, leading researchers to seek new diagnostic and treatment methods. One promising avenue is the development of targeted therapies and rapid diagnostic tests using recognition molecules. The pharmaceutical industry is increasingly exploring nucleic acid-based therapeutics. However, producing long oligonucleotides, especially aptamers, poses significant production challenges. Objectives: This study aims to demonstrate the efficacy of using molecular modeling, supported by experimental procedures, for altering aptamer nucleotide sequences while maintaining their binding capabilities. The focus is on reducing production costs and enhancing binding dynamics by removing nonfunctional regions and minimizing nonspecific binding. Methods: A molecular modeling approach was employed to elucidate the structure of a DNA aptamer, Gli-55, facilitating the truncation of nonessential regions in the Gli-55 aptamer, which selectively binds to glioblastoma (GBM). This process aimed to produce a truncated aptamer, Gli-35, capable of forming similar structural elements to the original sequence with reduced nonspecific binding. The efficiency of the truncation was proved by flow cytometry, fluorescence polarization (FP), and confocal microscopy. Results: The molecular design indicated that the new truncated Gli-35 aptamer retained the structural integrity of Gli-55. In vitro studies showed that Gli-35 had a binding affinity comparable to the initial long aptamer while the selectivity increased. Gli-35 internalized inside the cell faster than Gli-55 and crossed the blood–brain barrier (BBB), as demonstrated in an in vitro model. Conclusions: The success of this truncation approach suggests its potential applicability in scenarios where molecular target information is limited. The study highlights a strategic and resource-efficient methodology for aptamer development. By employing molecular modeling and truncation, researchers can reduce production costs and avoid trial and error in sequence selection. This approach is promising for enhancing the efficiency of therapeutic agent development, particularly in cases lacking detailed molecular target insights. [ABSTRACT FROM AUTHOR]

Simple Summary: T cell receptor-engineered T (TCR-T) cell therapy, which engineers the cells of the immune system to enhance their ability for targeting tumor cells, holds great promise, especially for solid tumors. One major challenge in this field is the identification of the right T Cell Receptor, which constitutes the core of developing these therapies. Our study introduces a new approach for the discovery and analysis of the entire repertoire of naturally-occurring antigen-specific TCRs utilizing state-of-the-art single-cell sequencing technology. This method could greatly improve the development of personalized cancer therapies and may lead to more effective treatments for a variety of tumors. Background: Adoptive cell therapy is the most promising approach for battling cancer, with T cell receptor-engineered T (TCR-T) cell therapy emerging as the most viable option for treating solid tumors. Current techniques for preparing TCR-T cell therapy provide a limited number of candidates TCRs, missing the comprehensive view of the repertoire, which may hinder the identification of the most effective TCRs. Methods: Dendritic cells were primed with immunogenic peptides of the antigen of interest to expand antigen-specific CD8 T lymphocytes from peripheral blood. Following that, the entire repertoire of naturally occurring antigen-specific TCRs was analyzed using single-cell RNA sequencing, alongside the assessment of the dominancy, transcriptome, and binding specificity of the obtained clonotypes, utilizing the TCRscape tool and ERGO-II neural network to identify the most effective candidate for TCR-T cell therapy development. Finally, TCR-T cells with the candidate TCR were obtained, followed by assessing their functionality and selectivity. Results: The developed protocol achieved a remarkable increase in the percentage of antigen-specific T cells by more than 200-fold, with more than 100 antigen-specific TCR clonotypes identified. The resulting TCR-T cells demonstrated high cytotoxicity and selectivity for the targeted antigen, indicating their potential to preferentially target tumor cells. Conclusions: This study offers a comprehensive approach for the discovery and analysis of not only few, but the entire repertoire of naturally occurring antigen-specific TCRs for TCR-T cell therapy development. Additionally, the proposed approach can be tailored to accommodate different types of antigens and MHC variants, making it a highly versatile tool for both research and clinical applications. [ABSTRACT FROM AUTHOR]

Rhinoviruses and respiratory enteroviruses remain among the leading causes of acute respiratory infections, particularly in children. Little is known about the genetic diversity of enteroviruses and rhinoviruses in pediatric patients with acute respiratory infections in Russia. We assessed the prevalence of human rhinoviruses/enteroviruses (HRV/EV) in 1992 children aged 0 to 17 years hospitalized with acute respiratory infections during the 2023–2024 epidemic season using PCR. The detection rate of HRV/EV was 11% (220/1992). We performed typing of 58 HRV and 28 EV viruses by partial sequencing of the VP1 gene. Rhinovirus A was the most common among HRV, followed by rhinovirus C; rhinovirus B was detected in only three cases. Enteroviruses were represented by all four species, with the EV-D68 genotype being the most frequently detected. Phylogenetic analysis of the VP1 fragment of EV-D68 showed that all our sequences belonged to the B3 subclade. We identified the first case of EV-C105 infection in Russia in a two-year-old girl hospitalized with pneumonia. Phylogenetically, the Novosibirsk strain EV-C105 was closely related to a strain discovered in France in 2018. This research helped to fill a critical gap in understanding the epidemiological landscape of HRV/EV in pediatric populations within Russia. [ABSTRACT FROM AUTHOR]

Natural polyphenolic compounds play a pivotal role in biological processes and exhibit notable antioxidant activity. Among these compounds, chlorogenic acid stands out as one of the most widespread and important polyphenols. The accurate detection of chlorogenic acid is crucial for ensuring the quality and classification of the raw materials used in its extraction, as well as the final products in the food, pharmaceutical, and cosmetics industries that contain this bioactive compound. Raman spectroscopy emerges as a powerful analytical tool, particularly in field applications, due to its versatility and sensitivity, offering both qualitative and quantitative analyses. By using the self-assembly of gold nanoparticles at liquid–liquid interfaces and the developed "aqua-print" process, we propose a facile and inexpensive route to fabricate enhanced substrates for surface-enhanced Raman spectroscopy with high reproducibility. To ensure substrate reliability and accurate molecule detection in SERS experiments, a benchmarking procedure was developed. This process involved the use of non-resonant rhodamine 6G dye in the absence of charge transfer and was applied to all synthesized nanoparticles and fabricated substrates. The latter revealed the highest enhancement factor of 4 × 104 for 72 nm gold nanoparticles among nanoparticle diameters ranging from 14 to 99 nm. Furthermore, the enhanced substrate was implemented in the detection of chlorogenic acid with a concentration range from 10 μM to 350 μM, demonstrating high accuracy (R2 > 99%). Raman mapping was employed to validate the good uniformity of the signal (the standard deviation was below 15%). The findings of this study were also supported by DFT calculations of the theoretical Raman spectra, demonstrating the formation of the chlorogenic acid dimer. The proposed method is strategically important for the development of the class of in-field methods to detect polyphenolic compounds in raw materials such as plants, extracted plant proteins, and polyphenolic compounds. [ABSTRACT FROM AUTHOR]

Sustainable development is one of the main directions of modern agriculture. First of all, sustainability in the agricultural sector can be achieved through the possible abandonment of traditional mineral fertilizers. Many decades of using these fertilizers have led to the degradation of arable soils and to soil and environmental pollution. As a result, this causes reductions in yields and the environmental quality of agricultural products and affects the health of the population. An alternative to traditional mineral fertilizers may be the use of innovative organomineral fertilizers obtained from local resources. These include manure, humus, compost, sediments, etc. In recent years, fertilizers obtained from the sapropels of the bottom sediments of lakes have become widespread. Their distinctive feature is the environmental friendliness and completeness of the content of chemical elements and substances necessary for the development and growth of plants. In addition, the methods of obtaining and applying these fertilizers allow us to talk about their effectiveness in use. The range of applications of these fertilizers is diverse, from use in the form of a dry extract applied directly to the soil to the use of liquid suspensions used at various stages of processing and from pre-sowing seed treatment to watering and spraying plants at different periods of vegetation. Moreover, an important aspect is the research work on the variational use of sapropel fertilizers on different crops, with different methods of production and concentrations and at different stages of processing. This publication contains the results of a study of the effect of the obtained innovative sapropel fertilizer on productivity, wheat grain quality, and economic efficiency (Triticum aestivum L.). To identify the optimal concentration of sapropel extract, laboratory studies were carried out to determine the germination energy and germination of wheat seeds of different varieties when they were soaked in various concentrations: 0.4, 0.8, 1.2, 1.6, and 2.0 g/L. The best indicators of germination energy and germination of wheat seeds during treatment with the extract were obtained at a concentration of 1.2 g/L. The research was conducted at an accredited variety testing laboratory. A field experiment was conducted in the fields of the agrobiological station of North Kazakhstan University named after Manash Kozybayev. The treatment of the seeds was carried out by soaking them in sapropel extract to evenly distribute the substance. The scheme of the field experiment included the option of using foliar treatment with a solution of sapropel extract at the tillering stage. As a result of the application of the obtained extract in the field, environmental and socio-economic efficiency was noted. The conducted field studies note its positive effect and effectiveness on the morphological, qualitative, and quantitative indicators of the wheat harvest. In the areas where wheat seeds were pretreated, as well as where foliar treatment with the resulting sapropel suspension was carried out, the best yield indicators were revealed. In these variants of the experiment with pre-sowing and pre-sowing and foliar treatment with the sapropel extract solution, the yield was 3.63 and 3.81 tons per hectare, respectively. The introduction of sapropel extract at the stage of seed treatment before sowing, as well as foliar processing of wheat at the tillering stage, will increase the efficiency and profitability of the agricultural industry and obtain a synergistic effect in the form of socio-economic efficiency and environmental safety of production. In our opinion, this will contribute to the development of sustainable agriculture and the production of environmental products. [ABSTRACT FROM AUTHOR]

Autoclave leaching of sulfide concentrates may produce various ferric secondary phases, depending on the arsenic content and temperature. Silver is converted to argentojarosite, from which it is not recoverable by standard cyanidation methods. To increase silver recovery, it is necessary to reduce the argentojarosite formation during autoclave leaching. This study was devoted to the influence of gypsum on the formation of secondary phases of ferric arsenate and the subsequent recovery of gold and silver by cyanidation. The addition of gypsum at a consumption of 0.1 g/g(concentrate) helped to increase silver extraction from 13.4 to 98% at cyanidation. Gold recovery was 99%. An increase in gypsum consumption contributed to the ferric arsenate sulfate formation with an increased sulfate sulfur content, and a decrease in the As/S(sulfate) molar ratio in the cake from 3.7 to 0.88 contributed to an increase in silver extraction at cyanidation of up to 98%. Basic ferric sulfate is not formed in this case, since according to EDS mapping, the distribution of arsenic and sulfur over ferric-containing particles is uniform. According to TCLP, stable, sparingly soluble ferric arsenate phases are formed and the cake obtained after cyanidation is stable and suitable for disposal, since the final arsenic concentration in the solution was 0.45 mg/dm3. [ABSTRACT FROM AUTHOR]

An interdigital transducer structure was fabricated from multilayer graphene on the surface of the Y Z -cut of a LiNbO3 ferroelectric crystal. The multilayer graphene was prepared by CVD method and transferred onto the surface of the LiNbO3 substrate. The properties of the multilayer graphene film were studied by Raman spectroscopy. A multilayer graphene (MLG) interdigital transducer (IDT) structure for surface acoustic wave (SAW) excitation with a wavelength of Λ = 60 μm was fabricated on the surface of the LiNbO3 crystal using electron beam lithography (EBL) and plasma chemical etching. The amplitude–frequency response of the SAW delay time line was measured. The process of SAW excitation by graphene IDT was visualized by scanning electron microscopy. It was demonstrated that the increase in the SAW velocity using graphene was related to the minimization of the IDT mass. [ABSTRACT FROM AUTHOR]

This paper presents a comprehensive exploration of advanced beamforming techniques tailored for millimeter-wave (mm-Wave) communication systems. In response to the burgeoning demand for higher data rates, coupled with the constraints of power consumption and hardware complexity, this study focuses on developing a hybrid beamforming framework optimized for downlink scenarios, specifically targeting groups of users based on the approximate symmetry of their channels. The primary innovation of this research lies in leveraging the symmetry of channels among near users to develop a group-based successive interference cancellation (SIC) algorithm. Unlike traditional approaches that address interference on a per-user basis, this algorithm utilizes channel symmetry within clusters of users to reduce computational complexity and improve the efficiency of SIC. By grouping users with symmetrical channel characteristics, the algorithm simplifies the interference management process while maintaining system performance. The proposed system demonstrates notable advantages over existing non-linear algorithms through extensive simulations and performance evaluations, particularly in terms of spectral efficiency and computational complexity. In this study, we further emphasize the importance of balancing spectral efficiency improvements with reduced computational demands, offering a nuanced trade-off that accommodates various operational requirements. The flexible optimization framework provided showcases the system's adaptability to diverse deployment scenarios and network configurations. [ABSTRACT FROM AUTHOR]

This study presents a case focused on sustainable farming practices, specifically the cultivation of tilapia (Mozambican and aureus species) in ponds with geothermal water. This research aims to optimize the hydrochemical regime of experimental ponds to enhance the growth metrics and external characteristics of tilapia breeders. The dataset encompasses the hydrochemical parameters and the fish feeding base from experimental geothermal ponds where tilapia were cultivated. Genetic algorithms (GA) were employed for hyperparameter optimization (HPO) of deep neural networks (DNN) to enhance the prediction of fish productivity in each pond under varying conditions, achieving an R 2 score of 0.94. This GA-driven HPO process is a robust method for optimizing aquaculture practices by accurately predicting how different pond conditions and feed bases influence the productivity of tilapia. By accurately determining these factors, the model promotes sustainable practices, improving breeding outcomes and maximizing productivity in tilapia aquaculture. This approach can also be applied to other aquaculture systems, enhancing efficiency and sustainability across various species. [ABSTRACT FROM AUTHOR]

This study is aimed at developing methods for the experimental and numerical simulation of the outflow of underexpanded gas jets into a rarefied medium. The numerical method is based on using Navier–Stokes equations in the continuum flow regime and the direct simulation Monte Carlo method in the transitional flow regime. The experimental method includes the modeling of jet flows in the LEMPUS-2 gas-dynamic setup with electron beam diagnostics for the jet density measurements. The results of the experimental modeling for the nozzles of various diameters confirm that a key parameter determining the jet structure is the Reynolds number based on the characteristic length ReL. The results of the numerical simulations agree well with the experimental data both for the maximum values of the ReL considered (approximately 30) when a barrel jet structure with Mach disks is formed and for the minimum values (approximately 4) when no Mach disks are formed. In the entire range of parameters, significant thermal nonequilibrium is observed at all jet segments where the measurements are performed. [ABSTRACT FROM AUTHOR]

This review paper focuses on the joint toxicity and interaction of carbon-based nanomaterials (CNMs) with co-existing pollutants in aquatic environments. It explores the potential harmful effects of chemical mixtures with CNMs on aquatic organisms, emphasizing the importance of scientific modeling to predict mixed toxic effects. The study involved a systematic literature review to gather information on the joint toxicity and interaction between CNMs and various co-contaminants in aquatic settings. A total of 53 publications were chosen and analyzed, categorizing the studies based on the tested CNMs, types of co-contaminants, and the used species. Common test models included fish and microalgae, with zebrafish being the most studied species. The review underscores the necessity of conducting mixture toxicity testing to assess whether the combined effects of CNMs and co-existing pollutants are additive, synergistic, or antagonistic. The development of in silico models based on the solid foundation of research data represents the best opportunity for joint toxicity prediction, eliminating the need for a great quantity of experimental studies. [ABSTRACT FROM AUTHOR]