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Abstract Mitochondrial dysregulation plays a significant role in the carcinogenesis. On the other hand, its destabilization strongly represses the viability and metastatic potential of cancer cells. Photodynamic and photothermal therapies (PDT and PTT) target mitochondria effectively, providing innovative and non-invasive anticancer therapeutic modalities. Cyanine dyes, with strong mitochondrial selectivity, show significant potential in enhancing PDT and PTT. The potential and limitations of cyanine dyes for mitochondrial PDT and PTT are discussed, along with their applications in combination therapies, theranostic techniques, and optimal delivery systems. Additionally, novel approaches for sonodynamic therapy using photoactive cyanine dyes are presented, highlighting advances in cancer treatment.

This paper focuses on the examination of the long-run relationship between money supply and selected national and global stock indices. Detailed knowledge of this relationship can be used by analysts, investors and monetary policy makers. Analysis of the relationship was performed using a 2-stage Engle-Granger cointegration. First, the stationarity of the time series was tested, then both the long-term OLS model and the short-term EC model were estimated. Time series were always tested on the longest period for which data were available. The longterm dependence of stock indices on the respective M2 was confirmed for the BOVESPA, FTSE100, S&P/BMV IPC, S&P BSE500, TSX and The 5000 Wilshire Small Cap Price Return indices. In contrast, the dependence between world money supply indicator GlobalM2, the stock index FTSEALL World, and the S&P500 index was not demonstrated. Additionally, no dependence was identified between the respective M2 and the DAX, PX, Nikkei225, KOSPI, SMI, SPCITIC300, Eurostoxx50, Willshire5000PR and ATX indices. Backward dependence of M2 on the stock index was found only for the Chinese SPCITIC300 index.

Anderson–Fabry Disease (AFD) is a rare, X-linked lysosomal storage disorder caused by a mutation in the α-Galactosidase A gene resulting in α-Galactosidase A enzyme (α-Gal A) deficiency. The metabolic defect leads to the progressive accumulation of glycosphingolipids and the structural and functional impairment of affected organs. Due to the inheritance pattern, male patients are hemizygous with more severe manifestations of the disease as compared to females who, in most cases, are heterozygous with delayed and variable clinical presentation caused by uneven X-chromosome inactivation. Fabry disease cases are often identified by targeted screening programs in high-risk groups, such as in patients with end-stage renal disease, premature stroke, or unexplained cardiomyopathy. Here, we describe a unique case of a homozygous female patient identified by a nationwide screening program in hypertrophic cardiomyopathy patients. Before the systematic screening, the patient had a diagnosis of hypertrophic obstructive cardiomyopathy and was treated accordingly, including with alcohol septal ablation to reduce the obstructive gradient. The confirmation of Fabry disease led to the discovery of the same variant in several members of her family. The identified variant was c.644A>G, p.Asn215Ser (p.N215S), which is known to cause predominant cardiac involvement with late onset of the disease. This variant is amenable to oral therapy with the small-molecule chaperone migalastat, which was started and then interrupted due to the recurrence of the patient’s migraine and then re-initiated again after two years. During this period, the patient received enzyme replacement therapy with agalsidase beta but developed progressively worsening venous access. Our case illustrates the importance of the systematic screening of patients with clinical evidence of hypertrophic cardiomyopathy in whom the routine diagnostic process fails to discover Fabry disease, in particular variants with late-onset cardiac manifestations. Many of the late-onset variants are amenable to orally active therapy with migalastat, which significantly improves the comfort of the treatment. Its long-term results are being analyzed by a large international “Follow-me” registry, which was designed to verify the validity of pivotal trials with migalastat in Fabry disease.

Abstract Immune checkpoints regulate the immune system response. Recent studies suggest that flavonoids, known as phytoestrogens, may inhibit the PD-1/PD-L1 axis. We explored the potential of estrogens and 17 Selective Estrogen Receptor Modulators (SERMs) as inhibiting ligands for immune checkpoint proteins (CTLA-4, PD-L1, PD-1, and CD80). Our docking studies revealed strong binding energy values for quinestrol, quercetin, and bazedoxifene, indicating their potential to inhibit PD-1 and CTLA-4. Quercetin and bazedoxifene, known to modulate EGFR and IL-6R alongside estrogen receptors, can influence the immune checkpoint functionality. We discuss the impact of SERMs on PD-1 and CTLA-4, suggesting that these SERMs could have therapeutic effects through immune checkpoint inhibition. This study highlights the potential of SERMs as inhibitory ligands for immune checkpoint proteins, emphasizing the importance of considering PD-1 and CTLA-4 inhibition when evaluating SERMs as therapeutic agents. Our findings open new avenues for cancer immunotherapy by exploring the interaction between various SERMs and immune checkpoint pathways.

This paper is devoted to the cognitive biases of decoy pricing, which has become the subject of interest of retail companies in recent years. The paper analyses the principles of the decoy effect with regard to consumer behaviour in the Czech Republic (which represents customers of the Eastern Europe). The analytical part of the paper focuses on examination of often irrational consumer decision-making process, with respect to age, gender, product group, and other factors. A combination of questionnaire survey (N=200) and interviews (N=32) was used. The results indicate a significant influence of the generation the consumer belongs to, further differences in decision-making according to gender, as well as differences in effects in various product categories. The findings may be utilised by companies considering the use of decoy pricing strategies in the Czech market.

The aim of this study was to estimate the effects of crossbreeding on milk production and milk components in crossbred Tsigai, Lacaune, and Improved Wallachian sheep used to create a synthetic Slovak dairy sheep population. The local breeds Tsigai and Improved Wallachian were crossed with the high-yielding breed Lacaune to increase milk yield. The effects of crossbreeding were evaluated based on breed and heterosis effects. The database used consisted of 23 018 lactations from 15 888 ewes. The effects of crossbreeding on milk production and fat and protein content were estimated using the restricted maximum likelihood method in REMLF90. Fixed effects on milk yield were also studied. In ewes with a 100% heterosis effect (ewes from purebred parents of different breeds), the heterosis effect increased milk production by 11.642 kg, milk fat production by 0.772 kg, and protein production by 0.565 kg per milking period. The effect of the Tsigai breed on milk production was -21.98 kg compared to Lacaune, while for the Improved Wallachian breed, the value was -38.58 kg. The Tsigai direct breed effect reduced fat production by 1.56 kg and protein production by 1.34 kg. The Improved Wallachian direct breed effect was -2.71 kg for fat production and -2.27 kg for protein production.

Abstract A simple, sensitive and quick HPLC method was developed for the determination of ketoprofen in cell culture media (EMEM, DMEM, RPMI). Separation was performed using a gradient on the C18 column with a mobile phase of acetonitrile and miliQ water acidified by 0.1 % (v/v) formic acid. The method was validated for parameters including linearity, accuracy, precision, limit of quantitation and limit of detection, as well as robustness. The response was found linear over the range of 3–100 μg/mL as demonstrated by the acquired value of correlation coefficient R2=0.9997. The described method is applicable for determination of various pharmacokinetic aspects of ketoprofen in vitro.

The achievement of profits when trading on the stock markets is conditioned by a quality analytical forecast of the development of stock prices in the coming period. This research attempts to compare the results of the ARIMA model and the ARIMA-GARCH model to forecast the development of stock prices on a sample of selected stocks from the Czech, German, Austrian, Polish and British markets. The 4 most liquid titles from each of the above-mentioned markets were selected for the sample of analyzed stocks. Available daily closing stock price data, mostly from the period 2000–2022, were used for the analysis. Research has shown that for most of the analyzed titles, it is more appropriate to use the ARIMA-GARCH model, which better captures variability for this data than just the ARIMA model. The quality of the selected model is evaluated by autocorrelation, heteroskedasticity tests, and Theil´s inequality coefficient.

Bcr-Abl is an oncoprotein with aberrant tyrosine kinase activity involved in the progression of chronic myeloid leukemia (CML) and has been targeted by inhibitors such as imatinib and nilotinib. However, despite their efficacy in the treatment of CML, a mechanism of resistance to these drugs associated with mutations in the kinase region has emerged. Therefore, in this work, we report the synthesis of 14 new 2,6,9-trisubstituted purines designed from our previous Bcr-Abl inhibitors. Here, we highlight 11b, which showed higher potency against Bcr-Abl (IC50 = 0.015 μM) than imatinib and nilotinib and exerted the most potent antiproliferative properties on three CML cells harboring the Bcr-Abl rearrangement (GI50 = 0.7–1.3 μM). In addition, these purines were able to inhibit the growth of KCL22 cell lines expressing Bcr-AblT315I, Bcr-AblE255K, and Bcr-AblY253H point mutants in micromolar concentrations. Imatinib and nilotinib were ineffective in inhibiting the growth of KCL22 cells expressing Bcr-AblT315I (GI50 > 20 μM) compared to 11b–f (GI50 = 6.4–11.5 μM). Molecular docking studies explained the structure–activity relationship of these purines in Bcr-AblWT and Bcr-AblT315I. Finally, cell cycle cytometry assays and immunodetection showed that 11b arrested the cells in G1 phase, and that 11b downregulated the protein levels downstream of Bcr-Abl in these cells.

The rising prevalence of obesity in children calls for new strategies for the provision of effective care by a multidisciplinary team. Telemedicine has overall proven to be an effective tool for promoting a healthy lifestyle. The main objective of the current paper is to present the protocol of our ongoing CardioMetabolic Prevention (CAMP) study and compare its design with published studies on telemedicine in paediatric obesity. Additionally, we analysed the preliminary anthropometric and laboratory data to test the efficacy of our 12-week intensive program that combines in-person and telemedicine support. The program demonstrated a positive impact on body mass index (BMI) and its z-scores in 21 adolescents, and BMI in 18 participating parents. However, we found no effect on body composition, waist circumference, cardiometabolic parameters, or fitness evaluated via a 6-min walk test in adolescents. In conclusion, the combination of in-person and telemedicine intensive support over 35 h delivered by a multidisciplinary team can be beneficial not only for adolescents with obesity but also for their parents. The ongoing CAMP study serves as a platform for precision medicine in future decisions regarding anti-obesity medication in adolescents with obesity.

Abstract Purpose Post-operative atrial fibrillation (PoAF) occurs in ~ 30% of patients after cardiac surgery. The etiology of PoAF is complex, but a disbalance in autonomic systems plays an important role. The goal of this study was to assess whether pre-operative heart rate variability analysis can predict the risk of PoAF. Methods Patients without a history of AF with an indication for cardiac surgery were included. Two-hour ECG recordings one day before surgery was used for the HRV analysis. Univariate and multivariate logistic regression, including all HRV parameters, their combination, and clinical variables, were calculated to find the best predictive model for post-operative AF. Results One hundred and thirty-seven patients (33 women) were enrolled in the study. PoAF occurred in 48 patients (35%, AF group); the remaining 89 patients were in the NoAF group. AF patients were significantly older (69.1 ± 8.6 vs. 63.4 ± 10.5 yrs., p = 0.002), and had higher CHA2DS2-VASc score (3 ± 1.4 vs. 2.5 ± 1.3, p = 0.01). In the multivariate regression model, parameters independently associated with higher risk of AF were pNN50, TINN, absolute power VLF, LF and HF, total power, SD2, and the Porta index. A combination of clinical variables with HRV parameters in the ROC analysis achieved an AUC of 0.86, a sensitivity of 0.95, and a specificity of 0.57 and was more effective in PoAF prediction than a combination of clinical variables alone. Conclusion A combination of several HRV parameters is helpful in predicting the risk of PoAF. Attenuation of heart rate variability increases the risk for PoAF.

TET proteins (methylcytosine dioxygenases) play an important role in the regulation of gene expression. Dysregulation of their activity is associated with many serious pathogenic states such as oncological diseases. Regulation of their activity by specific inhibitors could represent a promising therapeutic strategy. Therefore, this review describes various types of TET protein inhibitors in terms of their inhibitory mechanism and possible applicability. The potential and possible limitations of this approach are thoroughly discussed in the context of TET protein functionality in living systems. Furthermore, possible therapeutic strategies based on the inhibition of TET proteins are presented and evaluated, especially in the field of oncological diseases.

The article discusses selected poetry by Darko Suvin against the background of his theoretical writings about science fiction, utopia and poetry. It argues that Suvin’s poetry estranges the ideological view of the present and history as an inevitable reproduction of injustice and alienation. The focus is on several poems included in the collections The Long March: Notes on the Way 1981–1984 (1987) and Defined by a Hollow: Essays on Utopia, Science Fiction, and Political Epistemology (2010), as well as in “Three Long Poems 2000–2016” (2016) and “Poems of Old Age (2002–17)” (2017) available on the author’s website.

The aim of this study was to estimate across-country genetic correlations for calving traits (birth weight, calving ease) in the Limousine breed. Correlations were estimated for eight populations (Czech Republic, joint population of Denmark, Finland, and Sweden, France, Great Britain, Ireland, Slovenia, Switzerland, and Estonia). An animal model on raw performance accounting for across-country interactions (AMACI) was used. (Co)variance components were estimated for pairwise combinations of countries. Fixed and random effects were defined by each country according to its national genetic evaluation system. The average across-country genetic correlation for the direct genetic effect was 0.85 for birth weight (0.69–0.96) and 0.75 for calving ease (0.62–0.94). The average correlation for the maternal genetic effect was 0.57 for birth weight and 0.61 for calving ease. After the estimation of genetic parameters, the weighted bending procedure was used to compute the full Interbeef genetic correlation matrix. After bending, direct genetic correlations ranged from 0.62 to 0.84 (with an average of 0.73) for birth weight and from 0.58 to 0.82 (with an average of 0.68) for calving ease.

Welded joints on various pipelines, especially steam pipelines of fossil power plants, are exposed to high pressure and temperature of steam during operation. The applied stress and temperature together with the chemical composition and microstructure of the material have a major influence on the damage growth in these joints. Growth of defects as a time-dependent event, the sensitivity of the material to damage due to stress temperature and others plays a major role. In the case of steam pipes of fossil power plants, this is mainly creep damage. Early detection of these defects, especially at their initial stage, can help in managing the service life and thereby reducing the costs for operation, both by minimizing unplanned shutdowns as well as by planning any repairs in time. The work is focused on the detection of defect indications, especially creep damage occurring in weld joints and heat-affected areas. The aim is to distinguish manufacturing defects of welded joints from indications of early crack growth by ultrasonic testing. Indications from manufacturing defects may also be detected during testing and, if detected, will be evaluated in the same way as defects that are primarily targeted by the testing techniques. Several different techniques were tested on samples cut from the operated steam pipeline systems and compared with the results of metallographic analyses on selected parts.

Increasing requirements to minimize the frequency and duration of shutdowns of nuclear power plants have led to the need to address the implementation of ultrasonic testing of welded pipe connections at operating temperature. In practice, the pipes are made of carbon and stainless steel. Laboratory ultrasound tests were performed on two types of test pieces with different geometry and with homogeneous and heterogenous welds. The measurement was done within a temperature range of 50°C to 200°C in increment of 50°C. The aim of the performed measurements was to verify the detection of artificial defects created by electric discharge machining (EDM) in the root area of the weld on the carbon steel side by a selected test system and an impact of the change in focal laws (FLs) due to temperature on sizing. Together with this was evaluated the influence of elevated temperature on the determination of defect dimensions and impact of the test system, including ultrasonic, cooling, and handling subsystems for detection, sizing and using in the limited space of nuclear power plants. An inspection procedure and a safe workflow were created ss part of the testing. Both procedures were necessary for testing at elevated temperatures from the point of view of occupational safety and for carrying out individual test steps to maintain the repeatability of testing. The inspection procedure was subsequently qualified.

Vine-growing for the production of wine constitutes one of the major areas of agriculture of Czechia, and in recent years it has been qualitatively improved. The purpose of this study is to express the effects of climate change on the structure of wine production and consumption in the Czech Republic in connection with the growing local popularity of white wine consumption. The current consumer preferences of wine consumers in the Czech Republic (characterized by the growing popularity of white wines) are not in line with the effects of future climate change associated with the assumption of growing vine varieties suitable for the production of red wines. The methodology of the following study is based especially on the evaluation of statistical data about vine growing and wine production of Czechia and a research investigation about consumers’ preferences in the consumption of wines in Czechia. The effect of long-term climate change in the region are likely to lead to an increase in growing areas, especially in favour of vine varieties suitable for the production of red or rosé wines. The harvest of wine grapes, the hectare yield of grapes and the production of wine in Czechia do not show a significant development trend in the long-term time series of 2000–2019. Thus, in the future, the development of viticulture in Czechia will be influenced mainly by the location of the planted area of vineyards or the development of consumer habits and preferences.

Treatment of metastatic cancer is one of the biggest challenges in anticancer therapy. Curcumin is interesting nature polyphenolic compound with unique biological and medicinal effects, including repression of metastases. High impact studies imply that curcumin can modulate the immune system, independently target various metastatic signalling pathways, and repress migration and invasiveness of cancer cells. This review discusses the potential of curcumin as an antimetastatic agent and describes potential mechanisms of its antimetastatic activity. In addition, possible strategies (curcumin formulation, optimization of the method of administration and modification of its structure motif) to overcome its limitation such as low solubility and bioactivity are also presented. These strategies are discussed in the context of clinical trials and relevant biological studies.

The system of Czech technical standards for geometric accuracy assumes that the designer determines the functional geometric parameters for a specific building. By calculation, he verifies them in the so-called “geometric plan” in the project documentation. The functional geometric parameters should be determined primarily for critical elements, i.e. for structures whose geometric accuracy is important for the execution of subsequent works, such as technologies requiring high precision and specific structures. The assumption is that designers will incorporate variations in geometric accuracy primarily in the development of the spatial parameters of the structures, which should ensure that the dimensional requirements for the completed structures will be met. One of these parameters is headroom. The design of headroom must respect the minimum height requirements prescribed by legislation, and where appropriate, by technical standards. At the same time, the design must respect the technological possibilities of the construction of individual structures – geometric deviations. To comply with the dimensional requirements for the completed structures, the geometric accuracy deviations should be determined in accordance with the requirements of the technical standards for the execution of the individual parts of the building structures and/or for their design. The aim of this article is to establish a calculation procedure for determining the safe design clearance so that the requirements of the legislation are met after implementation. The increase is determined based on a calculation procedure of the limiting geometric deviations that may affect the resulting headroom.

The objective of the present study was to estimate the genetic parameters for the scrotal circumference of bulls of beef breeds in the Czech Republic. The used database for the years 1996-2020 comprised information on the scrotal circumference measurements from 22 065 bulls of 19 pure breeds and crossbred animals of the Beef Simmental, Charolais, and Hereford breeds. After adjustments, the database contained 16 404 records. To test the influence of systematic fixed effects, the GLM/SAS procedure using the least-squares method was applied. The contemporary group, weight and age of the bulls were included as significant systematic environmental effects (< 0.05). The genetic parameters were determined by a single-trait model using the AIREMLF90 program. The heritability coefficient of the scrotal circumference was 0.27. Environmental correlations of the scrotal circumference with the bull weight were moderate and positive (r = 0.2), but the correlations between the age in days and the scrotal circumference were almost zero (r = 0.03). The results indicate that the scrotal circumference of beef cattle breeds provides sufficiently high genetic variability that can be used to identify individuals with an above-average circumference and, in this way, increase the probability of selection of a young bull with a better reproduction potential.

The aim of this study was to assess the impact of incorporating genomic data using the single-step genomic best linear unbiased prediction (ssGBLUP) method compared to the best linear unbiased prediction (BLUP) method on the reliability of breeding values for age at first calving, calving interval, and productive longevity at 78 months in Charolais cattle. The study included 48,590 purebred Charolais individuals classified into four subgroups based on genotyping and performance records. The results showed that considering genotypes significantly improved genomic estimated breeding values (GEBV) reliability across all categories except nongenotyped individuals. For young genotyped individuals, the increase in reliability was up to 27% for both sexes. The highest average reliability was achieved for genotyped proven bulls and cows with performance records, and the inclusion of genomic data further improved the reliability by up to 22% and 21% for cows and bulls, respectively. The gain in reliability was observed mainly during the first three calvings, and then the differences decreased. The imported individuals showed lower estimated breeding values (EBV) and GEBV reliabilities than the domestic population, probably due to the weak genetic connection with the domestic population. However, when the progeny of imported heifers were sired by domestic bulls, the reliability increased by up to 24%. For nongenotyped individuals, only a slight increase in reliability was observed; however, the number of genotyped individuals in the population was still relatively small.

Predicting responses of plankton to variations in essential nutrients is hampered by limited in situ measurements, a poor understanding of community composition, and the lack of reference gene catalogs for key taxa. Iron is a key driver of plankton dynamics and, therefore, of global biogeochemical cycles and climate. To assess the impact of iron availability on plankton communities, we explored the comprehensive bio-oceanographic and bio-omics data sets from Tara Oceans in the context of the iron products from two state-of-the-art global scale biogeochemical models. We obtained novel information about adaptation and acclimation toward iron in a range of phytoplankton, including picocyanobacteria and diatoms, and identified whole subcommunities covarying with iron. Many of the observed global patterns were recapitulated in the Marquesas archipelago, where frequent plankton blooms are believed to be caused by natural iron fertilization, although they are not captured in large-scale biogeochemical models. This work provides a proof of concept that integrative analyses, spanning from genes to ecosystems and viruses to zooplankton, can disentangle the complexity of plankton communities and can lead to more accurate formulations of resource bioavailability in biogeochemical models, thus improving our understanding of plankton resilience in a changing environment.

Abstract A targeted shaping of complex femtosecond pulse waveforms and their characterization is essential for many spectroscopic applications. A 4f pulse shaper combined with an advanced pulse characterization technique should, in the idealized case, serve this purpose for an arbitrary pulse shape. This is, however, violated in the real experiment by many imperfections and limitations. Although the complex waveform generation has been studied in-depth, the comparison of the effects of various experimental factors on the actual pulse shape has stayed out of focus so far. In this paper, we present an experimental study on the targeted generation and retrieval of complex pulses by using two commonly-used techniques: spatial-light-modulator (SLM)-based 4f pulse shaper and second-harmonic generation frequency-resolved optical gating (FROG) and cross-correlation FROG (XFROG). By combining FROG and XFROG traces, we analyze the pulses with SLM-adjusted complex random phases ranging from simple to very complex waveforms. We demonstrate that the combination of FROG and XFROG ensures highly consistent pulse retrieval, irrespective of the used retrieval algorithm. This enabled us to evaluate the role of various experimental factors on the agreement between the simulated and actual pulse shape. The factors included the SLM pixelation, SLM pixel crosstalk, finite laser focal spot in the pulse shaper, or interference fringes induced by the SLM. In particular, we observe that including the SLM pixelation and crosstalk effect significantly improved the pulse shaping simulation. We demonstrate that the complete simulation can faithfully reproduce the pulse shape. Nevertheless, even in this case, the intensity of individual peaks differs between the retrieved and simulated pulses, typically by 10–20% of the peak value, with the mean standard deviation of 5–9% of the maximum pulse intensity. We discuss the potential sources of remaining discrepancies between the theoretically expected and experimentally retrieved pulse.

Plants can be infected with multiple viruses. High-throughput sequencing tools have enabled numerous discoveries of multi-strain infections, when more than one viral strain or divergent genomic variant infects a single plant. Here, we investigated small interfering RNAs (siRNAs) in a single strawberry plant co-infected with several strains of strawberry mottle virus (SMoV), strawberry crinkle virus (SCV) and strawberry virus 1 (StrV-1). A range of plants infected with subsets of the initial viral species and strains that were obtained by aphid-mediated transmission were also evaluated. Using high-throughput sequencing, we characterized the small RNA fractions associated with different genotypes of these three viruses and determined small RNA hotspot regions in viral genomes. A comparison of virus-specific siRNA (vsiRNA) abundance with relative viral concentrations did not reveal any consistent agreement. Strawberry mottle virus strains exhibiting considerable variations in concentrations were found to be associated with comparable quantities of vsiRNAs. Additionally, by estimating the specificity of siRNAs to different viral strains, we observed that a substantial pool of vsiRNAs could target all SMoV strains, while strain-specific vsiRNAs predominantly targeted rhabdoviruses, SCV and StrV-1. This highlights the intricate nature and potential interference of the antiviral response within a single infected plant when multiple viruses are present.

Dysregulation of iron homeostasis is one of the important processes in the development of many oncological diseases, such as pancreatic cancer. Targeting it with specific agents, such as an iron chelator, are promising therapeutic methods. In this study, we tested the cytotoxicity of novel azulene hydrazide-hydrazone-based chelators against pancreatic cancer cell lines (MIA PaCa-2, PANC-1, AsPC-1). All prepared chelators (compounds 4-6) showed strong cytotoxicity against pancreatic cancer cell lines and high selectivity for cancer cell lines compared to the healthy line. Their cytotoxicity is lower than thiosemicarbazone-based chelators Dp44mT and DpC, but significantly higher than hydroxamic acid-based chelator DFO. The chelator tested showed mitochondrial and lysosomal co-localization and its mechanism of action was based on the induction of hypoxia-inducible factor-1-alpha (HIF-1α), N-myc downstream-regulated gene-1 (NDRG1) and transferrin receptor 1 (TfR1). This strongly implies that the cytotoxic effect of tested chelators could be associated with mitophagy induction. Lipinski's rule of five analyses was performed to determine whether the prepared compounds had properties ensuring their bioavailability. In addition, the drug-likeness and drug-score were calculated and discussed.

One of the key challenges linked with future food and nutritional security is to evaluate the interactive effect of climate variables on plants’ growth, fitness, and yield parameters. These interactions may lead to unique shifts in the morphological, physiological, gene expression, or metabolite accumulation patterns, leading to an adaptation response that is specific to future climate scenarios. To understand such changes, we exposed spring wheat to 7 regimes (3 single and 4 combined climate treatments) composed of elevated temperature, the enhanced concentration of CO2, and progressive drought stress corresponding to the predicted climate of the year 2100. The physiological and metabolic responses were then compared with the current climate represented by the year 2020. We found that the elevated CO2 (eC) mitigated some of the effects of elevated temperature (eT) on physiological performance and metabolism. The metabolite profiling of leaves revealed 44 key metabolites, including saccharides, amino acids, and phenolics, accumulating contrastingly under individual regimes. These metabolites belong to the central metabolic pathways that are essential for cellular energy, production of biosynthetic pathways precursors, and oxidative balance. The interaction of eC alleviated the negative effect of eT possibly by maintaining the rate of carbon fixation and accumulation of key metabolites and intermediates linked with the Krebs cycle and synthesis of phenolics. Our study for the first time revealed the influence of a specific climate factor on the accumulation of metabolic compounds in wheat. The current work could assist in the understanding and development of climate resilient wheat by utilizing the identified metabolites as breeding targets for food and nutritional security.

ABSTRACT Sphingolipids are essential building blocks of eukaryotic membranes and important signaling molecules that are regulated tightly in response to environmental and physiological inputs. While their biosynthetic pathway has been well-described, the mechanisms that facilitate the perception of sphingolipid levels at the plasma membrane remain to be uncovered. In Saccharomyces cerevisiae, the Nce102 protein has been proposed to function as a sphingolipid sensor as it changes its plasma membrane distribution in response to sphingolipid biosynthesis inhibition. We show that Nce102 redistributes specifically in regions of increased sphingolipid demand, e.g., membranes of nascent buds. Furthermore, we report that the production of Nce102 increases following sphingolipid biosynthesis inhibition and that Nce102 is internalized when excess sphingolipid precursors are supplied. This finding suggests that the total amount of Nce102 in the plasma membrane is a measure of the current need for sphingolipids, whereas its local distribution marks sites of high sphingolipid demand. The physiological role of Nce102 in the regulation of sphingolipid synthesis is demonstrated by mass spectrometry analysis showing reduced levels of hydroxylated complex sphingolipids in response to heat stress in the nce102Δ deletion mutant. We also demonstrate that Nce102 behaves analogously in the widespread human fungal pathogen Candida albicans, suggesting a conserved principle of local sphingolipid control across species. IMPORTANCE Microorganisms are challenged constantly by their rapidly changing environment. To survive, they have developed diverse mechanisms to quickly perceive stressful situations and adapt to them appropriately. The primary site of both stress sensing and adaptation is the plasma membrane. We identified the yeast protein Nce102 as a marker of local sphingolipid levels and fluidity in the plasma membrane. Nce102 is an important structural and functional component of the membrane compartment Can1 (MCC), a plasma membrane microdomain stabilized by a large cytosolic hemitubular protein scaffold, the eisosome. The MCC/eisosomes are widely conserved among fungi and unicellular algae. To determine if Nce102 carries out similar functions in other organisms, we analyzed the human fungal pathogen Candida albicans and found that Nce102 responds to sphingolipid levels also in this organism, which has potential applications for the development of novel therapeutic approaches. The presented study represents a valuable model for how organisms regulate plasma membrane sphingolipids.

Probing buried interfaces in thin films is a crucial task in many fields, including optical coating. Ultrafast acoustics provide a means to characterize the interfaces by using an acoustic wave localized on the nanometer scale. We provide a brief overview of our thorough study of the interface between SiOxNy thin films and Si substrate by using both single-color and broadband picosecond acoustics. The experiment allows us to track the effect of stoichiometry on the acoustics wave propagation and transition over the layer-substrate interface. To optimize the experiment, we also created simulations to study the effect of optoacoustic layer thickness. We show that the used Ti layer features an optimum thickness between 5-10 nm to reveal details of the interface properties.

The targeted generation of fs pulses is essential for a variety of applications and it is routinely carried out by 4f pulse shapers. However, this seemingly simple task is complicated by hidden experimental limitations, such as modulator crosstalk or pixelation. We present an approach to overcome this issue by using a high-precision phase plate with a phase change characterized with λ/500 precision. We generated pseudorandom pulses using a 4f pulse shaper by using a structured PMMA plate with the high-precision predefined shape made by the SPDT machine. We study the accuracy, reproducibility, as well as the sufficiency, and limits of the method. The generated pulses are characterized using the FROG method. The reconstructed pulses’ shapes and their spectral phases are compared to the results of simulations.

SARS-CoV-2 is a serious viral pathogen, and agents that inhibit its replication are in high demand. In the present work, we prepared two novel tryptanthrin derivates bearing a thiosemicarbazone moiety as potential antiviral agents. Both compounds displayed potent chelation activity against Fe(III/II) ion-associated COVID-19. The molecular docking results suggest that the compounds can display significant affinity towards SARS-CoV-2 papain-like proteases and SARS-CoV-2 main proteases. In addition, administering T8H-TSC can repress viral replication in the used model (Vero cells). Moreover, the therapeutic potential of the prepared compounds was predicted and analysed in terms of Lipinski’s rules, drug-likeness and drug score.

This paper shows that the flexibility of time as a potential of Computer Assisted Language Learning (CALL) proves the sustainability of its latest stage -- Ubiquitous CALL. Firstly, the ideas of the Third Millennium Pedagogy are combined with the ethical and philosophical principles of sustainable education. One of the descriptors of the sustainable education -- its durability is then compared with the principle of time flexibility in e-learning. On this theoretical base, the ideas of Ubiquitous Learning in general and Ubiquitous CALL (U-CALL) in particular are developed. Two comparable cases of the research aimed at the time flexibility of e-learning in foreign language education are described. The former one was conducted in 2016, the later in 2008. Similar results in time flexibility prove that e-learning in language education can be omnipresent, fulfilling the demands on Ubiquitous CALL. The durability of time flexibility proven by the real-life examples indicates the sustainability of U-CALL.

The article focuses on investments as a tool for solving economic development problems of the national economy. Based on the analysis of macroeconomic systems' development factors, it is concluded that it is necessary to accelerate economic development to ensure national competitiveness within the current global economy. The necessity of forming the organizational mechanism for the country's economic growth at a transitional stage of development is substantiated. The analysis of foreign investments in Ukraine is carried out. The paper defines the key points, tools, and measures for forming the corresponding mechanism on the example of Ukraine as an economic system in the transitional stage of development. The organizational scheme for economic growth by executive authorities is proposed. One of the critical roles in this mechanism is assigned to the Investment Department and Independent National Science Council; tasks and functions of these units in the structure of the agency are described.

Eight types of capsules containing Bifidobacterium animalis subsp. lactis Bb12 with addition of inulin and/or ascorbic acid were prepared by emulsion method with milk protein matrix or by extrusion method with alginate matrix. The size of protein and alginate capsules containing only Bb12 was 204 ± 18 µm and 1.7 ± 0.1 mm, respectively. Addition of both inulin (1% w/w) and ascorbic acid (0.5% w/w) increased the size of alginate capsules. Both methods of encapsulation prevented efficiently the manifestation of Bb12 cell metabolic activity. All types of encapsulation provided higher resistance of Bb12 cells to the conditions of a model gastrointestinal tract (GIT) compared to free cells. The influence of co-encapsulation with inulin (1% w/w) and ascorbic acid (0.5% w/w) on viability in model GIT was not demonstrable in alginate capsules but it was significant in protein capsules. The most efficient was co-encapsulation in a protein matrix with 1% w/w inulin and 0.5% w/w ascorbic acid.

This article describes the Knihověda.cz portal, which represents an essential infrastructure for esearching Czech book history until 1800. The portal includes three parts: its core consists of a atabase comprised of five partial bibliographic databases. This interface contains complete data on printed Bohemica and manuscripts created before 1800 and a modern bibliography for research into Czech book history. The second element of the portal is Map of Printed Production in Bohemia and Moravia up to 1800, which provides interactive access to known printed editions dating back to the Middle Ages and Early Modern Period in the territory of today’s Czech Republic; it also allows for their visualisation according to various criteria. The third element created within the project is the online Encyclopaedia of Books in the Czech Middle Ages and Early Modern Period; its explanation of book history can serve educational purposes at both high schools and universities. A use case study of the history of books from the Rudolfinian period in the Czech lands (1576–1612) supplements the information provided about the portal.

The paper analyses and compares two italian librettos written in the 1st half of the 18th century: Agostino Piovene' libretto of the opera Porsena, performed in Venice during the carnival seasons of 1712 and 1713; and the libretto by Pietro Pariati written for the festa teatrale Costanza e Fortezza, performed in Prague in 1723 at the coronation of the Holy Roman Emperor Charles VI as King of Bohemia. Both librettos are inspired by historical events documented by the Roman historian Livy (59 BC – AD 17), recounting the overthrow of the last Tarquin king and the subsequent siege of Rome by Porsenna who tried to help restore the Tarquin dynasty and, according to Livy, failed to do so. Before arriving at the Vienna court in 1714, Pariati lived in Venice and thus was probably familiar with Piovene's libretto. The paper argues that the differences between the two librettos are caused also by the fact that Pariati in his Costanza e Fortezza from 1723 adapted the characters as well as the overall tone of certain episodes to serve the current dynastic and political interests of Charles VI. The paper is based on the close reading of selected character lines, the main points of comparison being the characters and their portrayal, as well as different adaptations of particular episodes in both librettos. The most apparent differences between the two adaptations are understandably caused by the different genres (Piovene's dramma per musica being an opera seria, while Pariati's festa teatrale was rather a form of courtly entertainment written in celebration of a ruler). The deeper and more fundamental difference, though, lies in Pariati's implicit defence of the Pragmatic Sanction expressed through allegorical nuances in the dialogue. One of the key differences, which upholds Charles VI's politics, is the Romans' adamant refusal of peace secured through marriage between the enemies of Rome and Roman girls in Costanza e Fortezza; while in Piovene's story, the Romans are willing to negotiate with their enemies about a marriage offer. The other key difference, perhaps surprising in the context of the Habsburg rule, is the Costanza e Fortezza's greater emphasis on the concept of republican freedom that the Romans gained in opposition to the tyranny of the Tarquin dynasty. The paper will explain the particular emphasis on these themes in Pariati's work, in light of the political situation in which it was written. The paper builds upon the authors previous study The Giovanni Bononcini's Opera Muzio Scevola (1710) and the Johann Joseph Fux' Festa teatrale Costanza e Fortezza (1723). From a Music Dramma to an Allegory published in 2018 in the Supplementum to the journal Musicologica Brunensia.

IL-6 signaling is involved in the pathogenesis of a number of serious diseases, including chronic inflammation and cancer. Targeting of IL-6 receptor (IL-6R) by small molecules is therefore an intensively studied strategy in cancer treatment. We describe the design, synthesis, and characteristics of two new bis-pentamethinium salts 5 and 6 (meta and para) bearing indole moieties. Molecular docking studies showed that both compounds have the potential to bind IL-6R (free energy of binding −9.5 and −8.1 kcal/mol). The interaction with IL-6R was confirmed using microscale thermophoresis analyses, which revealed that both compounds had strong affinity for the IL-6R (experimentally determined dissociation constants 26.5 ± 2.5 nM and 304 ± 27.6 nM, respectively). In addition, both compounds were cytotoxic for a broad spectrum of cancer cell lines in micromolar concentrations, most likely due to their accumulation in mitochondria and inhibition of mitochondrial respiration. In summary, the structure motif of bis-pentamethinium salts represents a promising starting point for the design of novel multitargeting compounds with the potential to inhibit IL-6 signaling and simultaneously target mitochondrial metabolism in cancer cells.

Due to ongoing climate change, forests are expected to face significant disturbances more frequently than in the past. Appropriate management is intended to facilitate forest regeneration. Because European temperate forests mostly consist of trees associated with ectomycorrhizal (ECM) fungi, understanding their role in these disturbances is important to develop strategies to minimize their consequences and effectively restore forests. Our aim was to determine how traditional (EXT) and nonintervention (NEX) management in originally Norway spruce (Picea abies) forests with an admixture of European larch (Larix decidua) affect ECM fungal communities and the potential to interconnect different tree species via ECM networks 15 years after a windstorm. Ten plots in NEX and 10 plots in EXT with the co-occurrences of Norway spruce, European larch, and silver birch (Betula pendula) were selected, and a total of 57 ECM taxa were identified using ITS sequencing from ECM root tips. In both treatments, five ECM species associated with all the studied tree species dominated, with a total abundance of approximately 50% in the examined root samples. Because there were no significant differences between treatments in the number of ECM species associated with different tree species combinations in individual plots, we concluded that the management type did not have a significant effect on networking. However, management significantly affected the compositions of ECM symbionts of Norway spruce and European larch but not those of silver birch. Although this result is explained by the occurrence of seedlings and ECM propagules that were present in the original forest, the consequences are difficult to assess without knowledge of the ecology of different ECM symbionts.