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Background: The duration of apnoeic oxygenation with high-flow nasal oxygen is limited by hypercapnia and acidosis and monitoring of arterial carbon dioxide level is therefore essential. We have performed a study in patients undergoing prolonged apnoeic oxygenation where we monitored the progressive hypercapnia with transcutaneous carbon dioxide. In this paper, we compared the transcutaneous carbon dioxide level with arterial carbon dioxide tension. Methods: This is a secondary publication based on data from a study exploring the limits of apnoeic oxygenation. We compared transcutaneous carbon dioxide monitoring with arterial carbon dioxide tension using Bland–Altman analyses in anaesthetised and paralysed patients undergoing prolonged apnoeic oxygenation until a predefined limit of pH 7.15 or PCO2 of 12 kPa was reached. Results: We included 35 patients with a median apnoea duration of 25 min. Mean pH was 7.14 and mean arterial carbon dioxide tension was 11.2 kPa at the termination of apnoeic oxygenation. Transcutaneous carbon dioxide monitoring initially slightly underestimated the arterial tension but at carbon dioxide levels above 10 kPa it overestimated the value. Bias ranged from −0.55 to 0.81 kPa with limits of agreement between −1.25 and 2.11 kPa. Conclusion: Transcutaneous carbon dioxide monitoring provided a clinically acceptable substitute for arterial blood gases but as hypercapnia developed to considerable levels, we observed overestimation at high carbon dioxide tensions in patients undergoing apnoeic oxygenation with high-flow nasal oxygen.

This article aims to verify the impact of the reduced IP Box tax rate on the revenues of gaming companies and Gibrat’s Law stating that firm growth is independent of a company’s size. The dynamic panel-data models estimated in this article using GMM, FE panel data and OLS methods were created based on data of 673 companies from 11 countries. We show that small gaming firms are growing faster than their larger rivals. Thus, we reject Gibrat’s Law. We did not find evidence that IP Box supports the firm’s growth except for the Wielkopolskie Voivodeship. More chances for IP Box’s (reduced to 5% income tax rate being in force in Poland since 2019) effects are given to firms with more remarkable and dynamic changes in capital intensity, intangibility and inventory. The gaming industry in Wielkopolska benefits more from IP Box than the rest of Poland.

Just as innovations contribute to building a competitive advantage, the level of intellectual property protection constitutes the international competitiveness of national economies and determines the market attractiveness for foreign direct investments. In this light, the paper analyses the impact of the amendment of February 13, 2020, to the Code of Civil Procedure Act and some other acts, introducing the so-called specific actions in cases related to intellectual property against the situation of innovators, including beneficiaries of the IP box relief, i.e. defence or preventive instruments in the event of a lawsuit or possible dispute. There is a risk of tax authorities questioning the legitimacy of the use of IP box based on qualified IP, i.e. copyright to a computer program. The potential dispute between the taxpayer and the tax authorities will primarily concern the resolution of what is a “computer program” under copyright law and the creative nature of the activity carried out by the taxpayer benefiting from the IP box relief. Effective from July 1, 2020, changes to the procedural proceedings in cases in the field of intellectual property introduced by the amendment to the Code of Civil Procedure protect the taxpayer’s interests using the IP box.

Despite significant efforts to limit the use of fossil fuels, SO2 remains a major air pollutant that adversely affects human health and the environment, especially in heavily industrialized regions of developing countries. Consequently, effective and sustainable methods of SO2 monitoring remain vital issues for detector development. However, despite decades of progress, current solutions based on resistive sensors remain limited by poor sensing performance of semiconducting materials when operated at room temperature and thus suffer from high power consumption due to heating. One solution could be to employ novel 2D semiconductor nanomaterials like MoS2, which have shown good room-temperature performance for gases such as NO2 and NH3. However, they have also shown limited response to other gases, which on the other hand, can be improved by substitutional doping. Consequently, this work investigates, employing density functional theory, the doping of MoS2 with Si, P, Cl, Ge, and Se to improve its SO2 sensing capability. The results show that P doping facilitates all desired effects with the electronic bandgap of MoS2 preserved at 0.72 nm–2 doping concentration, molecule-sheet charge transfers enhanced by 300%, and moderate binding energies that enable effective surface diffusion of SO2 at 300 K.

This article demonstrates the changes that have occurred in the fashion sector during COVID-19. It outlines the complexity of assessing the liquidity level of retail trade companies. Moreover, it gives an overview of the key information included in the financial statements of fashion companies and highlights key points crucial to determining the liquidity risk of these companies. The article also presents the results of two models; these were estimated using the Arellano–Bover / Blundell–Bond linear dynamic panel-data estimator. Results present the real impact of COVID-19 on the liquidity of Polish fashion and retail trade companies (measured by cash holdings or cash ratio) during the analysed period of time. The analysed data cover the 11 quarters from Q1 2019 to Q3 2021 and were obtained from the quarterly financial statements of the 108 public companies listed on the Warsaw Stock Exchange and NewConnect (Poland). The findings show that the fashion sector has lower liquidity than the broader retail trade sector. However, fashion companies during COVID-19 obtained higher cash ratios than retail trade companies. This article is a research-supported summary of the most important aspects of assessing the liquidity of fashion companies in light of the changes that have occurred in the industry due to the COVID-19 crisis.

New structurally diverse groups of C8-substituted caffeine derivatives were synthesized and evaluated for their chemical and biological properties. Mass spectrometry, FT-IR, and NMR characterizations of these derivatives were performed. The cytotoxic activity of the derivatives was estimated in vitro using human red blood cells (RBC) and in silico pharmacokinetic studies. The antioxidant capacity of the compounds was analyzed using a ferrous ion chelating activity assay. The ability of the derivatives to protect RBC from oxidative damage, including the oxidation of hemoglobin to methemoglobin, was assessed using a water-soluble 2,2′-azobis(2-methyl-propionamidine) dihydrochloride (AAPH) as a standard inducer of peroxyl radicals. The level of intracellular oxidative stress was assessed using the fluorescent redox probe 2′,7′-dichlorodihydrofluorescein diacetate (DCF-DA). The results indicate that all derivatives are biocompatible compounds with significant antioxidant and cytoprotective potential dependent on their chemical structure. In order to explain the antioxidant and cytoprotective activity of the derivatives, a mechanism of hydrogen atom transfer (HAT), radical adduct formation (RAF), or single electron transfer (SET), as well as the specific interactions of the derivatives with the lipid bilayer of RBC membrane, have been proposed. The results show that selected modifications of the caffeine molecule enhance its antioxidant properties, which expands our knowledge of the structure–activity relationship of caffeine-based cytoprotective compounds.

In my article, I formulate and describe the demand to remove the term obyczajność (propriety) from the Penal Code. In the course of the analysis, I will attempt to prove that its presence in the Act is an example of cultivating a terminological tradition that dates back to the partitions period and was started for a reason that is currently out­dated – the general language was insufficient to describe sexual crimes. I also show that due to the discrepancy between the general and legal language, the use of the term obyczajność may mislead a non-professional interpreter of a legal text. The text con­cludes with a more precise description of the titular demand, i.e. a proposal to change the title of Chapter 25 of the Penal Code.

The purpose of the research paper is to analyse the factors affecting remote work in terms of the selected socio-economic criteria and to determine which elements contribute the most to the development of sustainable work. In addition, the study describes the issues of remote education at the academic level and the challenges faced by academic teachers during the COVID-19 pandemic. The whole is embedded in the issues of occupational health and safety, with particular emphasis on the psychosocial aspects of the occupational safety of academic teachers in Poland. In the research process, the TOPSIS multi-criteria analysis tool (technique for order of preference by similarity to ideal solution) was used, as well as AHP (analytical hierarchy process), as an auxiliary method. The use of these methods made it possible to select the most important variable and to determine the ranking of factors affecting the analysed problem. Findings: According to the conducted research, the most important factor affecting the safety of remote work—in relation to the selected sustainability criteria—is overwork/workload. An equally important element was stress during remote work, as well as the organization of time, with consideration to the balance between work and home duties. The research has shown that the selected aspects of remote work can have a significant impact on the achievement of sustainable development goals by a given organization, and in relation to individuals, on the quality of life and the sense of safety and health at work.

Luminescent Ln3+ -doped nanoparticles (NPs) functionalised with the desired organic ligand molecules for haemocompatibility studies were obtained in a one-pot synthesis. Chelated aromatic organic ligands such as isophthalic acid, terephthalic acid, ibuprofen, aspirin, 1,2,4,5-benzenetetracarboxylic acid, 2,6-pyridine dicarboxylic acid and adenosine were applied for surface functionalisation. The modification of the nanoparticles is based on the donor-acceptor character of the ligand-nanoparticle system, which is an alternative to covalent functionalisation by peptide bonding as presented in our recent report. The aromatic groups of selected ligands absorb UV light and transfer their excited-state energy to the dopant Eu3+ ions in LaF3 and SrF2 NPs. Herein, we discuss the structural and spectroscopic characterisation of the NPs and the results of haemocompatibility studies. Flow cytometry analysis of the nanoparticles' membrane-binding is also presented.

In the study, we confirm that reporting entities increase discretionary revenue when their pre-managed operating income and net earnings are slightly lower than the consensus forecast by analysts for the fourth quarter. The novelty of this article is that introducing IFRS 15 significantly mitigates the increase of discretionary revenue when pre-managed operating income is slightly lower than the fourth quarter consensus on operating income. We do not find the implementation of IFRS 15 to have an impact on discretionary revenue if reporting entities are unable to meet the fourth quarter revenue and net earnings consensus by a small amount.

The development of an effective therapy aimed at restoring muscle dysfunctions in clinical and sports medicine, as well as optimizing working activity in general remains an urgent task today. Modern nanobiotechnologies are able to solve many clinical and social health problems, in particular, they offer new therapeutic approaches using biocompatible and bioavailable nanostructures with specific bioactivity. Therefore, the nanosized carbon molecule, C

International audience; Communities of herbivorous insects on individual host trees may be driven by processes ranging from ongoing development via recent microevolution to ancient phylogeny, but the relative importance of these processes and whether they operate via trophic interactions or herbivore movement remains unknown. We determined the leaf phenology, trunk diameter, genotype, and neighbourhood of sessile oak trees (Quercus petraea), and sampled their caterpillar communities. We found that leaf development across a time period of days related to free-living caterpillars, which disappeared with leaf age. Tree growth across decades is related to increased parasitism rate and diversity of herbivores. The microevolution of oak trees across millennia is related to the abundance of leaf-mining casebearers, which is higher on more homozygous oaks. However, oak genome size was not important for any guild. In contrast to most previous studies, the phylogenetic distance of oaks from their neighbours measured in millions of years was associated with higher abundances of entire caterpillar guilds. Furthermore, on trees surrounded by only distantly related tree species, parasitism tended to be lower. Lower parasitism, in turn, was associated with higher abundances of codominant caterpillar species. Neighbourhoods and traits of trees were also related to community composition and diversity, but not to the average wingspans or specialization of species, consistent with the assembly of herbivore communities being driven by leaf traits and parasitism pressure on trees rather than by insect movement among trees. However, movement in rarer species may be responsible for concentration effects in more phylogenetically distant neighbourhoods. Overall, we suggest that the assembly of insects on a tree is mostly driven by trophic interactions controlled by a mosaic of processes playing out over very different time scales. Comparisons with the literature further suggest that, for oak trees, the consequences of growing amongst distantly related tree species may depend on factors such as geographic region and tree age.

The purpose of the study is to identify earnings management behaviour prior to mergers and acquisitions with a particular emphasis on the role of acquirers’ ownership structures. We build panel regression models describing the associations between earnings management proxies and measures of mergers and acquisitions with additional variables describing elements of acquirers’ ownership structures. In the study, we confirm that acquirers do not engage in upward management prior to mergers and acquisitions. We find, however, that managerial ownership reduces magnitudes of total upward real earnings management. The presence of institutional investors diminishes accrual-based upward earnings management prior to mergers and acquisitions.

In the last few years Indonesia has been experiencing a new wave of Muslim revival. In addition to the growing popularity of conservative and even radical Muslim ideologies such as Wahhabism and Salafism, this de facto multi-religious society is facing a strong trend towards religious segregation. Indonesians are looking for new forms of their religious manifestation and expressions of their piety. One of the most vivid examples of Muslim separation from other religions is the perumahan syariah, a new form of gated communities in Indonesia. The article describes the growing phenomenon of closed neighborhoods where residents’ lives are restricted by Sharia law. The paper first describes the roots of the current religious revival and its impact on the social situation, then deepens the definition of gated communities in the context of perumahan syariah as well as controversies linked to the topic. In conclusion, the possible implications for social life in Indonesia are presented.

Conjugating an anticancer drug of high biological efficacy but large cytotoxicity with a “transporting” molecule of low toxicity constitutes a valuable approach to design safe drug delivery system. In the present study, doxorubicin (DOX) a drug of large cardiotoxicity was chemically conjugated to a C60-fullerene. The synthesized molecule, a fullerene-doxorubicin conjugate (Ful-DOX), was characterized using the 1H NMR and MALDI TOF mass spectrometry. The absorption and fluorescence spectra and dynamic light scattering of the conjugate were recorded in an aqueous solution, while the impact on viability of several cancer cell lines of the free DOX and the conjugate was compared using the SRB and WST-1 assays. A low antiproliferative activity of the conjugate as compared to the free DOX is a consequence of the presence of fullerene moiety in the former, which is also responsible for the conjugate aggregation in an aqueous solution. Unlike free DOX, these aggregates cannot pass through the nuclear membrane (as demonstrated by the confocal microscopy measurements), which makes them marginally cytotoxic.

The objective of our study is to investigate whether the ownership structure of a company, including ownership concentration, managerial ownership and the presence of institutional investors, affects accrual earnings management practices. We first modelled discretionary accruals using the modified approach of Jones (1991), and then we built the model describing the relationship between discretionary accruals and elements of ownership structure of companies and control variables, determining regression using the least square method. We provided evidence of negative dependence between the magnitude of accrual earnings management and shareholder concentration. We do not corroborate the relationship between accrual earnings management and managerial ownership. The presence of institutional investors reduces the magnitude of accrual earnings management. We do not provide evidence that the presence of State Treasury affects accrual earnings management. We do not confirm that accrual earnings management is used for meeting or beating earnings benchmarks.

The Pinus mugo complex comprises closely related pines in different taxonomic ranks, which commonly occur in major European mountain chains. This large and polymorphic complex has been, and still is, a considerable challenge for taxonomists due to highly variable phenotypical characteristics within particular taxa, ongoing hybridization in sympatric populations, lack of distinct morphological species-specific determinants, and the absence of distinct genetic differentiation among them. Moreover, cytogenetic data on pines from this complex are very scarce. Therefore, in this study, we used C-banding methods and flow cytometric analysis in order to provide new data on karyotypical features and DNA content of three closely-related pines from the Pinus mugo complex, i.e., Pinus mugo (Turra), Pinus uliginosa (Neumann), and Pinus × rhaetica (Brügger) and to gain more insight into the taxonomic relationships between these pines. Our results confirmed that the basic number of chromosome is the same amongst the analyzed taxa (2n = 2x = 24), and that the karyotypes have a similar morphology. The number of secondary constrictions (SCs) and C-banding patterns differed slightly between P. mugo, P. uliginosa and P. × rhaetica. The nuclear DNA content (2C/pg) among analyzed taxa is from 46.41 pg for P. mugo and P. × rhaetica to 46.48 pg for P. uliginosa. For each of these pines, certain taxa-specific cytogenetic determinants were identified. Our results indicate that they may represent two different taxa, and so their names should not be used interchangeably in scientific literature.

Molecular organization of non-chlorinated (Pn) and chlorinated (PCln) esters of perylene tetracarboxylic acid with four lateral alkyl chains composed of n carbon atoms (n = 4, 10) in spin-coated films has been studied. The Pn dyes have shown a strong tendency for aggregation in the ground and excited state, which can be limited by long alkyl chains. Fluorescence quantum yield (FQY) of their film does not exceed the value of 0.04 and is far below that of the strongly diluted toluene solution (0.87). Chlorine atoms attached in the bay positions of the PCln dyes caused twisting of the perylene skeleton, which resulted in longer intermolecular distances and weaker interactions between molecules in films. In this way, an aggregation process was reduced and the role of the alkyl chains length as a steric hindrance was suppressed. However, FQY of the PCln films is below 0.24, because of its low value measured for the monomeric form in diluted solution (0.35). Furthermore, the concentration effect of the Pn and PCln dyes dispersed in poly (methyl methacrylate) (PMMA) on types of aggregates formed by them and on FQY value has been studied. FQY of the Pn derivatives increased with the drop of their concentration in PMMA up to the values of 0.59 and 0.69 for the dyes with shorter and longer alkyl chains, respectively. This makes them promising materials for application in organic light emitting diodes. In turn, FQY of the PCln derivatives in PMMA matrix was in the range of 0.17–0.37 and does not change in a regular way with dyes concentration.

The development of an effective therapy aimed at restoring muscle dysfunctions in clinical and sports medicine, as well as optimizing working activity in general remains an urgent task today. Modern nanobiotechnologies are able to solve many clinical and social health problems, in particular, they offer new therapeutic approaches using biocompatible and bioavailable nanostructures with specific bioactivity. Therefore, the nanosized carbon molecule, C60 fullerene, as a powerful antioxidant, is very attractive. In this study, a comparative analysis of the dynamic of muscle soleus fatigue processes in rats was conducted using 50 Hz stimulation for 5 s with three consistent pools after intraperitoneal administration of the following antioxidants: C60 fullerene (a daily dose of 1 mg/kg one hour prior to the start of the experiment) and N-acetylcysteine (NAC; a daily dose of 150 mg/kg one hour prior to the start of the experiment) during five days. Changes in the integrated power of muscle contraction, levels of the maximum and minimum contraction force generation, time of reduction of the contraction force by 50% of its maximum value, achievement of the maximum force response, and delay of the beginning of a single contraction force response were analyzed as biomechanical markers of fatigue processes. Levels of creatinine, creatine phosphokinase, lactate, and lactate dehydrogenase, as well as pro- and antioxidant balance (thiobarbituric acid reactive substances, hydrogen peroxide, reduced glutathione, and catalase activity) in the blood of rats were analyzed as biochemical markers of fatigue processes. The obtained data indicate that applied therapeutic drugs have the most significant effects on the 2nd and especially the 3rd stimulation pools. Thus, the application of C60 fullerene has a (50–80)% stronger effect on the resumption of muscle biomechanics after the beginning of fatigue than NAC on the first day of the experiment. There is a clear trend toward a positive change in all studied biochemical parameters by about (12–15)% after therapeutic administration of NAC and by (20–25)% after using C60 fullerene throughout the experiment. These findings demonstrate the promise of using C60 fullerenes as potential therapeutic nanoagents that can reduce or adjust the pathological conditions of the muscular system that occur during fatigue processes in skeletal muscles.

An adsorption process of magnetite nanoparticles functionalized with aminated chitosan (Fe3O4-AChit) showing application potential in nanomedicine into cell membrane models was studied. The cell membrane models were formed using a Langmuir technique from three selected phospholipids with different polar head-groups as well as length and carbon saturation of alkyl chains. The research presented in this work reveals the existence of membrane model composition-dependent regulation of phospholipid-nanoparticle interactions. The influence of the positively charged Fe3O4-AChit nanoparticles on a Langmuir film stability, phase state, and textures is much greater in the case of these formed by negatively charged 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DPPG) than those created by zwitterionic 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and 2-oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine (POPC). The adsorption kinetics recorded during penetration experiments show that this effect is caused by the strongest adsorption of the investigated nanoparticles into the DPPG monolayer driven very likely by the electrostatic attraction. The differences in the adsorption strength of the Fe3O4-AChit nanoparticles into the Langmuir films formed by the phosphatidylcholines were also observed. The nanoparticles adsorbed more easily into more loosely packed POPC monolayer.

Luminescent Ln

The fundamental aspects related to the mechanisms of action of C60 fullerene nanoparticles on the level of the central nervous system in different experimental conditions are still unclear. Electrophysiological investigation and immunohistochemical techniques of c-fos expression were combined to determine which neural elements within the lumbar segments and in the central nucleus of the amygdala (CeA) are activated under skeletal muscle fatigue development with prior application of C60 fullerenes (dissolved in dimethyl sulfoxide and in distilled water, FDS). After high-frequency electrical stimulation of the triceps surae muscle, the main fatigue-related increases in the c-Fos expression level were registered ipsilaterally within lamina 1 and 5 of the lumbar segments and within the contralateral capsular part of the CeA. C60 fullerene pretreatment in animals with subsequent electrical stimulation induced a distinct (2–4 times) decrease in the level of Fos immunoreactivity in the observed structures in comparison with only fatigue-induced rats. It can be supposed that FDS, as antioxidant compound, can decrease the concentration of free radicals in fatigued tissue and reduce the transmission intensity of nociceptive information from muscles to the spinal cord and amygdala, thereby changing the level of c-Fos expression within the lumbar segments and CeA.

The photoisomerization and thermal relaxation processes of three amphiphilic azobenzene derivatives (LCAn) showing liquid-crystalline properties were studied in solutions and in monomolecular films formed using Langmuir and Langmuir-Blodgett techniques. The well-controlled isomeric state of LCAn in chloroform during the UV irradiation allowed to prepare spreading solutions containing trans isomers, cis isomers or their mixture and to investigate molecular organization in the Langmuir films made of them. Surface pressure-mean molecular area isotherms and compression modulus-surface pressure dependences delivered information on a thermodynamic state, phase transitions and intermolecular interaction in the monolayers. LCAn in the trans state create densely-packed films, in which the photoisomerization do not occur due to the lack of free volume for the change of the molecules conformation and their strong tendency for the H-type aggregation. However, the reversible switching of the LCAn conformation during cyclic photoisomerization and thermal relaxation processes was observed in the LB films initially deposited onto quartz substrates in the cis state, where molecules are loosely-packed and exist in the monomeric form. Kinetics and rate constants of the photoisomerization and thermal relaxation were determined based on the recorded absorption spectra in order to obtain information on their efficiency and on the impact of the replacement of the alkyl chain attached in the LCAn para position with the alkyloxy chain. Our research show that LCAn are promising materials for application in optical memories, logic gates and holographic gratings.

C60 fullerene is reported to directly interact with biomolecules, such as aromatic mutagens or anticancer drugs. Therefore, it is extensively studied for its potential application in the fields of drug delivery and chemoprevention. Understanding the nature of fullerene-drugs interactions might contribute to optimization and modification of the existing chemotherapy systems. Possible interactions between ICR-191, a model acridine mutagen, with well-established biophysical properties and mutagenic activity, and C60 fullerene aqueous solution were investigated by broad range of biophysical methods, such as Dynamic Light Scattering, Isothermal Titration Calorimetry, and Atomic Force Microscopy. Additionally, to determine biological activity of ICR-191-C60 fullerene mixtures, Ames mutagenicity test was employed. It was demonstrated that C60 fullerene interacts non-covalently with ICR-191 and has strong affinity to bacterial membranes. The obtained results provide practical insight into C60 fullerene interactions with aromatic compounds.

Solanum sisymbriifolium, a wild relative of the S. lycopersicum species, has been found to be resistant to numerous pathogens which cause severe diseases in Solanaceae crops. It would be highly desirable for species strongly affected by diseases (e.g. tomato) to contain the resistant genes found in their wild relatives. Solanum sisymbriifolium has been considered of potential interest for S. melongena L. breeding, as the former is resistant to several pathogens and resistant interspecific hybrids have been obtained. Additionally, several reports indicate that S. sisymbriifolium is useful for tomato gynogenic haploid production. It is still not quite clear whether S. sisymbriifolium can be crossed with S. lycopersicum and the development of hybrid progeny is possible. In our preliminary in vivo crossing, S. lycopersicum × S. sisymbriifolium diploid embryos were formed inside fruits, but their development was inhibited at the globular stage. To obtain F1 hybrids the embryo-rescue method was implemented. Globular embryos isolated 14–35 dap were cultured on various media showing varied morphogenic potencies. Most of the embryos did not develop on the used media but calli formed from the embryogenic cells in > 17% of the embryos, allowing hybrid plants to be obtained. Ten regenerants, which were adapted in pots containing soil, had morphological traits similar to the S. sisymbriifolium parent, including the plant habit, presence of prickles on shoots or white colour of flowers. The hybrid origin of the regenerants was confirmed by flow cytometry analysis of DNA content and KASP genotyping. The results indicated that S. lycopersicum can be hybridized with S. sisymbriifolium through interspecific hybridization to introduce novel traits for use in tomato-breeding programmes.

Effective targeting of metastasis is considered the main problem in cancer therapy. The development of herbal alkaloid Berberine (Ber)-based anticancer drugs is limited due to Ber’ low effective concentration, poor membrane permeability, and short plasma half-life. To overcome these limitations, we used Ber noncovalently bound to C60 fullerene (C60). The complexation between C60 and Ber molecules was evidenced with computer simulation. The aim of the present study was to estimate the effect of the free Ber and C60-Ber nanocomplex in a low Ber equivalent concentration on Lewis lung carcinoma cells (LLC) invasion potential, expression of epithelial-to-mesenchymal transition (EMT) markers in vitro, and the ability of cancer cells to form distant lung metastases in vivo in a mice model of LLC. It was shown that in contrast to free Ber its nanocomplex with C60 demonstrated significantly higher efficiency to suppress invasion potential, to downregulate the level of EMT-inducing transcription factors SNAI1, ZEB1, and TWIST1, to unblock expression of epithelial marker E-cadherin, and to repress cancer stem cells-like markers. More importantly, a relatively low dose of C60-Ber nanocomplex was able to suppress lung metastasis in vivo. These findings indicated that сomplexation of natural alkaloid Ber with C60 can be used as an additional therapeutic strategy against aggressive lung cancer.

Zirconium dioxide has been widely used in dental prosthetics. However, the improper mechanical treatment can induce changes in the microstructure of zirconium dioxide. From the viewpoint of mechanical properties and performance, the phase transitions of ZrO 2 from the tetragonal to the monoclinic phase induced by mechanical processing, are particularly undesirable. In this study, the phase transitions of yttrium stabilized zirconium dioxide (Y-TZP) induced by mechanical treatment are investigated by the scanning electron microscopy (SEM), atomic force microscopy (AFM) and powder diffraction (XRD). Mechanical stress was induced by different types of drills used presently in dentistry. At the same time the surface temperature was monitored during milling using a thermal imaging camera. Diffraction analysis allowed determination of the effect of temperature and mechanical processing on the scale of induced changes. The observed phase transition to the monoclinic phase was correlated with the methods of mechanical processing.

The use of zirconium oxide in dental implantology is rapidly increasing as it is regarded as being more aesthetical and biologically friendly than titanium oxide. The interaction of titanium oxide with cells and proteins has proven to be significantly affected by the inevitable atmospheric hydrocarbon contamination, defined as biological ageing. The latter has proven to be effectively reversed by UVC irradiation. Crystal structures of both Zr and Ti oxides are very similar, thus also ZrO2 is prone to contamination by hydrocarbons. In the present study we have characterized the chemical-physical changes occurring to ZrO2 after UVC irradiation. Firstly a reduction by 3-fold of carbon present on its surface. XRD analysis has indicated that UVC irradiation treatment does not affect the crystalline structure of ZrO2, suggesting that it is possible to improve cell attachment on the surface without sacrificing the mechanical strength of the material. In addition a chemical model of interaction of cell surface proteins with the almost carbon free ZrO2 surface obtainable after UVC irradiation is proposed, pointing to the important role likely played by integrins and RGD sequences originating in soluble proteins adsorbed at the cell/ZrO2 interface. Hence in clinical practice UVC photofunctionalization could improve the soft tissue seal around dental implants functioning as a valid barrier between implant and peri-implant bone, thereby improving the long-term success of implants.

The fundamental aspects related to the mechanisms of action of C60 fullerene nanoparticles on the level of the central nervous system in different experimental conditions are still unclear. Electrophysiological investigation and immunohistochemical techniques of c-fos expression were combined to determine which neural elements within the lumbar segments and in the central nucleus of the amygdala (CeA) are activated under skeletal muscle fatigue development with prior application of C60 fullerenes (dissolved in dimethyl sulfoxide and in distilled water, FDS). After high-frequency electrical stimulation of the triceps surae muscle, the main fatigue-related increases in the c-Fos expression level were registered ipsilaterally within lamina 1 and 5 of the lumbar segments and within the contralateral capsular part of the CeA. C60 fullerene pretreatment in animals with subsequent electrical stimulation induced a distinct (2–4 times) decrease in the level of Fos immunoreactivity in the observed structures in comparison with only fatigue-induced rats. It can be supposed that FDS, as antioxidant compound, can decrease the concentration of free radicals in fatigued tissue and reduce the transmission intensity of nociceptive information from muscles to the spinal cord and amygdala, thereby changing the level of c-Fos expression within the lumbar segments and CeA.

Magnetite nanoparticles are promising materials for application in magnetic resonance imaging, targeted drug delivery, enzyme immobilization and cancer therapies based on hyperthermia thanks to their biocompatibility, wide chemical affinity and superparamagnetic properties. However, there is still the lack of the knowledge of interactions between magnetite nanoparticles covered with the bioactive polymers and biological cells. In order to fulfil this gap, we have investigated interactions of newly synthetized magnetite nanoparticles functionalized with aminated chitosan (Fe3O4-aminated chitosan) and a model biological membrane made of dipalmitoylphosphatidylcholine (DPPC) using a Langmuir technique. Surface pressure-mean area per DPPC molecule isotherms and Brewster angle microscope images (BAM) recorded during compression of the two-component Fe3O4-aminated chitosan:DPPC films revealed the strong influence of the Fe3O4-aminated chitosan nanoparticles on the stability, phase state and structure of the phospholipid membrane. The studies on the adsorption/incorporation process of the Fe3O4-aminated chitosan nanoparticles showed that they can adsorb/incorporate into the DPPC model membrane at the surface pressure corresponding to this present in the cellular membrane under the biological conditions (35 mN·m−1). The number of the adsorbed/incorporated Fe3O4-aminated chitosan nanoparticles can be regulated by the nanoparticles concentration in the neighbourhood of the DPPC model membrane even at high surface pressure of 35 mN·m−1.

Betulin is a natural pentacyclic triterpenoid, possessing a lupane-structure, with a wide range of pharmacological activities. Its weak hydrosolubility hinders the biological activity of the compound and its derivatives. To circumvent this problem, we synthesized and tested in vitro three d-glycosaminosides of betulin. The structure of betulin was modified by incorporation of 2-amino-2-deoxy-d-gluco- and -d-galactopyranosyl moieties to its C-3 position. So far betulinyl glycosides containing these amino-sugars have not been reported in the literature. The structure of the studied derivatives was confirmed by 1H and 13C NMR spectroscopy as well as mass spectrometry. The 28-O-acetylbetulin-3-yl 2-amino-2-deoxy-β-d-glucopyranoside and betulin-3-yl 2-amino-2-deoxy-β-d-gluco- and β-d-galactopyranoside were tested against the human pathogenic fungi and Gram-positive and Gram-negative bacteria. Moreover, the MTT assay of their cytotoxicity was performed on the MCF-7 breast cancer cell line and on the HDFa, human dermal fibroblasts. The Ames test on mutagenic properties completed our biological assays.

Antimicrobial resistance is a major healthcare threat globally. Xanthines, including caffeine and pentoxifylline, are attractive candidates for drug repurposing, given their well-established safety and pharmacological profiles. This study aimed to analyze potential interactions between xanthines and aromatic antibiotics (i.e., tetracycline and ciprofloxacin), and their impact on antibacterial activity. UV-vis spectroscopy, statistical-thermodynamical modeling, and isothermal titration calorimetry were used to quantitatively evaluate xanthine-antibiotic interactions. The antibacterial profiles of xanthines and xanthine-antibiotic mixtures towards important human pathogens Staphylococcus aureus, Enterococcus faecium, Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, and Enterobacter cloacae were examined. Caffeine and pentoxifylline directly interact with ciprofloxacin and tetracycline, with neighborhood association constant values of 15.8–45.6 M− 1 and enthalpy change values up to -4 kJ M− 1. Caffeine showed antibacterial activity (minimum inhibitory concentration, 4–8 mg/mL) toward Gram-negative bacteria. Caffeine enhanced the antibacterial activity of the tested antibiotics in most pathogens tested. Antagonistic effects of caffeine were observed only with ciprofloxacin toward Gram-positive pathogens. Xanthines interact with aromatic antibiotics at the molecular and in vitro antibacterial activity level. Given considerable exposure to caffeine and pentoxifylline, these interactions are relevant for the effectiveness of antibacterial pharmacotherapy, and may help to identify optimal treatment regimens in the era of multidrug resistance.

The concept of programmable and reconfigurable soft matter has emerged in science in the last few decades and can be realized by photoisomerization of azobenzene derivatives. This possibility results in great application potential of these compounds in optical storage devices, molecular junctions of electronic devices, command layers of liquid crystal displays or holographic gratings. In this paper, we present the results of a study on the organization and isomerization of the non-ionic and amphiphilic methyl 4-[(E)-2-[4-(nonyloxy)phenyl]diazen-1-yl]benzoate (LCA) in a 2D layer architecture of Langmuir and Langmuir-Blodgett (LB) films supported by spectroscopic studies on LCA chloroform solutions. Our investigation has shown a significantly different molecular organization of LCA depending on the ratio of trans and cis isomers in the monolayers. Taking advantage of a relatively low packing density and aggregation strength in the cis-LCA monolayer, we demonstrated the reversible isomerization in the LB film initially formed of LCA molecules in the cis form, while in the trans-LCA monolayer this effect was not observed. Our approach allows the formation of a switchable monolayer made of the amphiphilic LCA showing liquid crystalline properties without introducing an ionic group into the molecule structure, mixing with another compound or changing the subphase pH to provide free space for the molecules' isomerization.

We formulated and analyzed a novel nanoformulation of the anticancer drug cisplatin (Cis) with C60 fullerene (C60+Cis complex) and showed its higher toxicity toward tumor cell lines in vitro when compared to Cis alone. The highest toxicity of the complex was observed in HL-60/adr and HL-60/vinc chemotherapy-resistant human leukemia cell sublines (resistant to Adriamycin and Vinculin, respectively). We discovered that the action of the C60+Cis complex is associated with overcoming the drug resistance of the tumor cell lines through observing an increased number of apoptotic cells in the Annexin V/PI assay. Moreover, in vivo assays with Lewis lung carcinoma (LLC) C57BL/6J male mice showed that the C60+Cis complex increases tumor growth inhibition, when compared to Cis or C60 fullerenes alone. Simultaneously, we conducted a molecular docking study and performed an Ames test. Molecular docking specifies the capability of a C60 fullerene to form van der Waals interactions with potential binding sites on P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP-1), and multidrug resistance protein 2 (MRP-2) molecules. The observed phenomenon revealed a possible mechanism to bypass tumor cell drug resistance by the C60+Cis complex. Additionally, the results of the Ames test show that the formation of such a complex diminishes the Cis mutagenic activity and may reduce the probability of secondary neoplasm formation. In conclusion, the C60+Cis complex effectively induced tumor cell death in vitro and inhibited tumor growth in vivo, overcoming drug resistance likely by the potential of the C60 fullerene to interact with P-gp, MRP-1, and MRP-2 molecules. Thus, the C60+Cis complex might be a potential novel chemotherapy modification.

The method of widening of the blue phase (BP) temperature range is presented. By means of polarising optical microscopy, we demonstrate that the temperature regime in which BP is stable is greatly enhanced by the cell thickness changes in mixtures of nematic liquid crystal (LC) and chiral dopant.

Matrix metalloproteinases (MMPs) are extracellular matrix degradation factors, promoting cancer progression. Hence, they could provide an enzyme-assisted delivery of doxorubicin (DOX) in cancer treatment. In the current study, the intercalation process of DOX and tetrapeptide&ndash, DOX, the product of the MMPs&rsquo, cleavage of carrier-linked DOX, into dsDNA was investigated using stationary and time-resolved fluorescence spectroscopy, UV-Vis spectrophotometry and isothermal titration calorimetry (ITC). The molecular dynamics (MD) simulations on the same tetrapeptide&ndash, DOX&hellip, DNA and DOX&hellip, DNA systems were also performed. The undertaken studies indicate that DOX and tetrapeptide&ndash, DOX can effectively bond with dsDNA through the intercalation mode, however, tetrapeptide&ndash, DOX forms less stable complexes than free DOX. Moreover, the obtained results demonstrate that the differences in DNA affinity of both forms of DOX can be attributed to different intercalation modes. Tetrapeptide&ndash, DOX shows a preference to intercalate into DNA through the major groove, whereas DOX does it through the minor one. In summary, we can conclude that the tetrapeptide&ndash, DOX intercalation to DNA is significant and that even the lack of non-specific proteases releasing DOX from the tetrapeptide conjugate, the presence of which is suggested by the literature for the efficient release of DOX, should not prevent the cytostatic action of the anthracycline.

Background Pentoxifylline (PTX) is a drug commonly used in the treatment of intermittent claudication. However, numerous research groups report that PTX also may potentially be used in the anticancer therapy following one of the main trends in the nowadays medicine - combined anticancer therapy. Scope of review The review concentrates on the reports revealing the potential use of PTX in cancer treatment. Major Conclusion: PTX is described to possess several properties which may be exploited in cancer treatment. The drug reportedly not only has anticancer activity itself, but also increases cancer cells susceptibility to radiation therapy and, additionally, reduces long-term side effects of this therapy. Furthermore, numerous research groups report that PTX may increase the anticancer potential of commonly used anticancer drugs such as cisplatin or doxorubicin as well as reduce side effects of these drugs. Significance PTX should be considered as a potential drug in the combined anticancer therapy.

Langmuir films formed of some fluorescent dyes, 3,4-bis-pentyl ester of 9,10-N-(n-pentylimide)-perylenetetracarboxylic acid, as well as their mixtures with arachidic acid, were studied. Surface pressure versus mean molecular area isotherms for Langmuir films were reordered and the alignment of molecules at the air–water interface was estimated. The isotherms show that the dye molecules do not lie flat onto the water surface but are tilted with respect to the normal to the interface. The surface pressure–area isotherms of Langmuir films formed from the dye/arachidic acid mixture provide evidence for phase separation of the components within almost the entire range of mole fractions. A repulsive interaction between molecules was observed in all two components of Langmuir films.

Human leukocyte antigen (HLA)-G is a class Ib molecule with restricted tissue distribution expressed on trophoblast cells and has been proposed to have immunomodulatory functions during pregnancy. Soluble HLA-G1 (sHLA-G1) can be generated by the shedding of membrane-bound HLA-G molecules; however, three soluble isoforms also exist (HLA-G5 to -G6). During pregnancy, it is unknown whether there is a correlation between sHLA-G levels in maternal and fetal blood. In 246 pregnancies, we have measured the levels of sHLA-G1/-G5 in maternal blood plasma samples from gestational week 20 (GW20) and at term, as well as in umbilical cord blood samples. Soluble HLA-G levels declined by 38.4% in maternal blood from GW20 to term, and sHLA-G levels were significantly lower in maternal blood at term than in GW20 (P