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When applied to functional analysis results, structured visual inspection criteria have resulted in improvements in the levels of agreement between raters as well as earlier identification of the function of challenging behavior. However, multistep criteria can be difficult to apply in real time, which could be a barrier to widespread adoption in practice. This study evaluated a Microsoft-Excel-based functional analysis decision support system (FADSS), which could aid behavior analysts with interpreting functional analysis results. Final overall agreement between the FADSS and post hoc visual inspection was high at 95%. Final overall agreement between the post hoc results generated by FADSS and ongoing results generated by FADSS was acceptable at 81%, representing a 50% increase in efficiency. These results indicate that FADSS could aid behavior analysts when interpreting functional analysis results in real time.

This study focuses on a unique collection of personal economic records and additional documents from the 20th century, belonging to a Catholic priest from Satu Mare County, Romania. The material is exceptional, as it represents a rare collection of written documents from the Hungarian-speaking region of the 20th century, authored by a Catholic priest. These records provide an in-depth look into the life of a priest, who, despite his clerical duties, maintained a strong connection to farming, a legacy from his farmer-herdsman parents of Swabian descent. The economic records, which span from 1949 to the 1960s, offer insights into the priest's personal and economic life. They include narratives about managing a parish, engaging in farming activities, and handling personal financial transactions. These documents not only reflect his efforts to balance religious responsibilities with agricultural interests but also illuminate the socio-economic conditions of the time. The study explores the priest's economic decisions, the value he placed on different assets, and his understanding of wealth in a changing society. It also examines the broader context of peasant embourgeoisement in 20th-century Romania, highlighting how a priest and his family navigated the transition from a traditional peasant lifestyle to a more bourgeois existence. This transition is evidenced by their adoption of modern goods and technologies, changes in family dynamics, and shifts in career strategies, reflecting the complex interplay between personal, economic, and social factors during a period of significant societal change. Overall, the paper offers a micro-historical perspective on the life of this 20th-century priest, providing valuable insights into his unique experiences and the broader socio-economic transformations of the era.

This paper presents a comprehensive dataset on the global trade dynamics of COVID-19-related medical products for the years 2019 and 2020. The dataset, derived from the BACI database, focuses on eight distinct product categories identified by six-digit codes. The trade flow data for 224 countries is structured as a multilevel network, with countries as nodes and product categories as layers. Directed edges represent trading activities, and edge weights are determined by the difference in exported values between 2019 and 2020. The dataset is provided in an edges-and-nodes format. Additionally, the associated R script transforms the data into the MuxViz R package format, facilitating further analysis and visualization of the dataset. The dataset is valuable for researchers in the field of foreign trade or medical products, and for decision-makers in these fields, whether at company or national level.

In bone marrow transplantation (BMT), hematopoiesis-reconstituting cells are introduced following myeloablative treatment, which eradicates existing hematopoietic cells and disrupts stroma within the hematopoietic tissue. Both hematopoietic cells and stroma then undergo regeneration. Our study compares the outcomes of a second BMT administered to mice shortly after myeloablative treatment and the first BMT, with those of a second BMT administered to mice experiencing robust hematopoietic regeneration after the initial transplant. We evaluated the efficacy of the second BMT in terms of engraftment efficiency, types of generated blood cells, and longevity of function. Our findings show that regenerating hematopoiesis readily accommodates newly transplanted stem cells, including those endowed with a robust capacity for generating B and T cells. Importantly, our investigation uncovered a window for preferential engraftment of transplanted stem cells coinciding with the resumption of blood cell production. Repeated BMT could intensify hematopoiesis reconstitution and enable therapeutic administration of genetically modified autologous stem cells.

Mutations in the splicing factor 3b subunit 1 (SF3B1) gene are frequent in myelodysplastic neoplasms (MDS). Because the splicing process is involved in the production of circular RNAs (circRNAs), we investigated the impact of SF3B1 mutations on circRNA processing. Using RNA sequencing, we measured circRNA expression in CD34+ bone marrow MDS cells. We defined circRNAs deregulated in a heterogeneous group of MDS patients and described increased circRNA formation in higher‐risk MDS. We showed that the presence of SF3B1 mutations did not affect the global production of circRNAs; however, deregulation of specific circRNAs was observed. Particularly, we demonstrated that strong upregulation of circRNAs processed from the zinc finger E‐box binding homeobox 1 (ZEB1) transcription factor; this upregulation was exclusive to SF3B1‐mutated patients and was not observed in those with mutations in other splicing factors or other recurrently mutated genes, or with other clinical variables. Furthermore, we focused on the most upregulated ZEB1‐circRNA, hsa_circ_0000228, and, by its knockdown, we demonstrated that its expression is related to mitochondrial activity. Using microRNA analyses, we proposed miR‐1248 as a direct target of hsa_circ_0000228. To conclude, we demonstrated that mutated SF3B1 leads to deregulation of ZEB1‐circRNAs, potentially contributing to the defects in mitochondrial metabolism observed in SF3B1‐mutated MDS.

The paper introduces the particle-induced X-ray emission analysis (PIXE) of two Hajdúböszörmény-type situlae from the eponymous Hajdúböszörmény I hoard (collection of the Hungarian National Museum, Budapest) and Sényő (collection of the Jósa András Museum, Nyíregyháza). Both situlae are representative types of the period between 1080 and 960 BC, Ha B1, or the ‘Hajdúböszörmény hoard horizon’ of the Hungarian Late Bronze Age. The obtained results are significant in that they are the very first to characterise the classic Hajdúböszörmény-type situla from their core distribution area, i.e., the region where this metal vessel type was presumably produced. The paper is focused on a description of the elemental composition of these tin bronze vessels, with particular attention on the grouping of their accompanying elements and the ratio of tin. The PIXE results suggest that a rather homogenous raw material was used to produce and repair these objects, which can be correlated with the CG16 Copper Group. The ratio of tin was relatively high, mostly around 9–10 wt%; low values were only identified on one of the repaired parts of the Sényő situla and a secondarily attached copper rivet.

Abstract Ion beam analysis (IBA) is an established method to determine the concentration and the distribution of elements in art and archaeological objects. However, especially for organic specimens, caution must be taken to avoid harmful effects. In this work, the possible modification of recent calf parchment samples by proton beam irradiation was investigated applying fluences (given as deposited charge per unit area) both within and beyond the usual analytical practice. Attenuated Total Reflection Fourier Transform Infra-red Spectroscopy (FTIR-ATR) and Optical Coherence Tomography (OCT) were employed to assess changes, inspected from the surface of the samples. Although both techniques are apt to detect alterations of parchment in general, in the case of particles, which deposit the majority of their energy below the surface these techniques could not detect changes at low fluences. However, a simple “bath test” (short immersion in liquid) proved that disintegration within the material had already happened. After the “bath test”, OCT and digital 3D microscopy were used to check the discontinuities in the material, especially for low fluences when the visual inspection might have missed them. Unfortunately, simply monitoring organic objects such as parchment during or after ion beam irradiation, non-destructively, is not sufficient to claim absolute harmlessness, as some studies in the past did. In line with our former findings using electron microscopy on cross sections, we found that 2.3 MeV protons with a deposited charge of 0.5 µC/cm2 caused no changes affecting the integrity of parchment but 2 µC/cm2 apparently did under the applied experimental conditions. To ensure the required analytical signal at a relatively low deposited charge, the detection system must be optimized for efficiency. Nevertheless, since the variability of the historic materials and the measurement set-ups are considerable, these values cannot be taken as absolutes, but only as guides, both for further IBA studies and for studies conducted in the past.

Abstract Ion beam analysis plays an important role in cultural heritage (CH) studies as it offers a combination of simultaneous and complementary analytical techniques (PIXE/PIGE/RBS) and spatially resolved mapping functions. Despite being considered non-destructive, the potential risk of beam-induced modifications during analysis is increasingly discussed. This work focuses on the impact of proton beams on parchment, present in our CH in form of unique historical manuscripts. Parchment is one of the organic, protein-based CH materials believed to be the most susceptible to radiation-induced changes. Various modification patterns, observed on parchment cross-sections by optical and electron microscopy are reported: discoloration (yellowing), formation of cavities and denaturation of collagen fibers. Considerable modifications were detected up to 100 µm deep into the sample for beam fluences of 4 µC/cm2 and higher. The presence of ultramarine paint on the parchment surface appears to increase the harmful effects of proton radiation. Based on our results, a maximum radiation dose of 0.5 µC/cm2 can be considered as ‘safe boundary’ for 2.3 MeV PIXE analysis of parchment under the applied conditions.

Absztrakt. Cikkemben feltérképezem a legfontosabb versenyelőnyöket, mely az online kereskedelemben, webáruházakban történő értékesítéshez, sikerességhez és népszerűséghez elengedhetetlenül fontos. A témával kapcsolatban számtalan szakirodalmat találhatunk. Évről évre több és több kutatás, felmérés készül a vásárlói értékről, a vásárlási szokásokról, fogyasztói magatartásról, a digitális transzformációról, amelyeket szeretnék összegezni és megfogalmazni, illetve kiemelni azokat a fő elemeket, melyek nélkül nem lenne hatékony az online értékesítés.

A correction to this paper has been published: https://doi.org/10.1007/JHEP05(2019)197

A correction to this paper has been published: https://doi.org/10.1007/JHEP07(2021)202

The glucosinolates of Brassicaceae plants are converted into bioactive isothiocyanates and other volatiles during a challenge by pathogens and other biotic stressors. However, the role of alternative downstream products with weaker potency (e.g., nitriles) is far from being fully understood. This study tested the possible synergistic antifungal interaction between various glucosinolate-derived nitriles and 2-phenylethyl isothiocyanate (PEITC) on 45 fungal strains, including endophytes from horseradish roots (Brassicaceae) and soil fungi, using an airtight system enabling the accurate study of extremely volatile antifungal agents. The median minimal inhibitory concentrations (MICs) were 1.28, 6.10, 27.00 and 49.72 mM for 1H-indole-3-acetonitrile (IAN), 3-phenylpropanenitrile (PPN), 4-(methylsulfanyl)-butanenitrile (MSBN) and 3-butenenitrile (BN, = allyl cyanide), respectively. Thus, nitriles were considerably weaker antifungal agents compared to PEITC with a median MIC of 0.04 mM. For the same nitriles, the median fractional inhibitory concentration indices (FICIs) of the combinations were 0.562, 0.531, 0.562 and 0.625, respectively. Altogether, 47.7%, 56.8%, 50.0% and 27.3% of tested fungal strains showed a synergistic antifungal activity (FICI ≤ 0.5) for the nitrile–isothiocyanate combinations, respectively. Hypocreales strains showed the least sensitivity towards the GSL decomposition products and their combinations. The mean MIC values for PEITC showed 0.0679 ± 0.0358, 0.0400 ± 0.0214, 0.0319 ± 0.0087 and 0.0178 ± 0.0171 mM for Hypocreales, Eurotiales, Glomerellales and Pleosporales, respectively. In addition, nitriles, especially IAN, also showed significant differences. For the same fungi, the median FICI values fell in the ranges of 0.61–0.67, 0.52–0.61, 0.40–0.50 and 0.48–0.67, respectively, depending on the nitrile. Our results suggest that glucosinolate-derived nitriles may enhance isothiocyanate antifungal activity and that they may play an active role in shaping the plant microbiome and contribute to the filtering of microbes by plants.

Abstract In previous work, [ arXiv:1905.01909 ], we have calculated the m ϱ /fπ ratio in the chiral and continuum limit for SU(3) gauge theory coupled to N f = 2, 3, 4, 5, 6 fermions in the fundamental representation. The main result was that this ratio displays no statistically significant N f -dependence. In the present work we continue the study of the N f -dependence by extending the simulations to N f = 7, 8, 9, 10. Along the way we also study in detail the N f -dependence of finite volume effects on low energy observables and a particular translational symmetry breaking unphysical, lattice artefact phase specific to staggered fermions.

Nasal drug delivery has been a focus of scientific interest for decades. A number of drug delivery systems and devices are available and have been highly successful in providing better and more comfortable therapy. The benefits of nasal drug delivery are not in question. The nasal surface provides an excellent context for the targeted delivery of active substances. In addition to the large nasal surface area and intensive absorption, the active substances delivered through the nose overcome the blood–brain barrier and can be delivered directly to the central nervous system. Formulations for nasal administration are typically solutions or liquid dispersed systems such as emulsions or suspensions. Formulation techniques for nanostructures have recently undergone intensive development. Solid-phase heterogeneous dispersed systems represent a new direction in pharmaceutical formulations. The wide range of possible examples and the variety of excipients allow for the delivery of a wide range of active ingredients. The aim of our experimental work was to develop a solid drug delivery system that possesses all of the above-mentioned advantageous properties. In developing solid nanosystems, we not only exploited the advantages of size but also the adhesive and penetration-enhancing properties of excipients. During formulation, several amphiphilic compounds with adhesion properties and penetration enhancing effects were incorporated. We used chlorpromazine (CPZ), which is mainly used in the treatment of psychotic disorders such as schizophrenia and bipolar disorder. Chlorpromazine has been previously investigated by our team in other projects. With the availability of previous methods, the analytical characterization of the drug was carried out effectively. Due to the frequent and severe side effects of the drug, the need for therapeutic dose reduction is indisputable. In this series of experiments, we succeeded in constructing drug delivery systems. Finely divided Na nanoparticles were formed using a Büchi B90 nanospray dryer. An important step in the development of the drug carrier was the selection of suitable inert carrier compounds. Particle size determination and particle size distribution analysis were performed to characterize the prepared nanostructures. As safety is the most important aspect of any drug formulation, all components and systems were tested with different biocompatibility assays. The tests performed demonstrated the safe applicability of our systems. The bioavailability of chlorpromazine was studied as a function of the ratio of the active ingredient administered nasally and intravenously. As described above, most nasal formulations are liquids, but our system is solid, so there is currently no tool available to accurately target this system. As a supplement of the project, a nasal dosing device was developed, corresponding to the anatomical structure; a prototype of the device was made using 3D FDM technology. Our results lay the foundation for the design and industrial scaling of a new approach to the design and production of a high-bioavailability nasal medicinal product.

Influencers are present in our everyday lives, we see them at events, in advertisments, TV and papers, and in their „natural habitat”: social media. It is not surprising considering that the fact that E-WOM has a stronger impact on consumer decision-making than traditional advertising techniques has been known for a long time. Moreover, advertisements are now consciously ignored by consumers, making influencer marketing an excellent alternative where the opinion leader formulates and publishes the message him- or herself. These individuals seem more approachable compared to traditional celebrities, as they provide insight into their daily lives making it easier to identify with them. Brands, in turn, can collaborate with the right influencers to create positive associations in the minds of consumers. Nowadays, consumers get the needed information about the products from social media and, as a result, make purchases, also they trust even an unknown individual’s recommendation more than brand ads. Consistent posting and the presence of socially accepted values in the posts are essential elements in influencer marketing, which must be complemented by active engagement with the followers. It may be worthwhile to start with a look at the number of the followers before starting a collaboration, but the results of the researchers came to a different conclusion. Some of them found that a large following bases does not always represent a real influencing force and it is more rewarding to focus on shared content and the brand–influencer fit. Others found that the number of followers correlated positively with consumer engagement. Interestingly however, even though followers recognize that they are encountering advertised content, they still use the information gained in their decision-making, and even a specifically urging and activating tone can encourage them to purchase. Thus authenticity plays a cruical role for both parties, and for this reason it is crucial how the product and the influencer itself is indicated in the advertised content.

The mechanism by which influencer marketing has emerged as a concept is far from new. In the world of advertising, where almost every minute the people are faced with an advertisement, people are becoming more immune to the traditional promotions. Influencer marketing is an excellent alternative for this issue, where the entities formulate and publish the message themselves. Due to the fact that opinion leaders may appear accessible in the eyes of followers, associating a brand with positively evaluated opinion leaders results a positive attitude toward the brand. There are factors which establish a fruitful cooperation between the parties, but they are hard to recognise, and even the researchers have different standpoint, for example with the number of the followers. However, a fallible image, the brand-influencer fit, attractiveness can surely strengthen the effectiveness. And surprisingly it does not necessarily lead to a negative perception of the opinion leader if followers recognize that their post contains advertisement.

Nowadays, there is almost no event, no advertisement, without a face of at least one famous person. The involvement of a consciously built personal brand in the promotion is almost inevitable, whether it be a medicine or eyewear brand, or a complete political party. Marketing also plays an increasingly important role in sports. Recently, several researchers have focused on building a personal brand for athletes. The primary purpose of my current research is to demonstrate how a sports team can pursue a marketing strategy based on personal branding. I would like to examine the change in the number of followers, the profitability of conscious selection and subsequent brand building, and the relative effectiveness of its steps. During my empirical study (a 21-day test period), I posted 9 personal branding posts on the Facebook page of the University of Debrecen’s Athletic Club’s Hockey Team, which were promoted by paid advertisements. To measure the results, I used data from the site and compared them to the metrics of the three 21-day cycles prior the experiment. After the period under review, the number of hockey team’s followers on Facebook has more than doubled. Even taking into account the organic impressions (The number of times any content from/about the Team’s Page entered a person's screen through unpaid distribution.) alone, the increase was still more than 120%, and the standard deviation of these appearances fell from above 100% on average to below 50%. The number of engaged users (The number of people who engaged with the Team’s Page. Engagement includes any click or story created.) peaked and rose on average and became more balanced. Earlier research and my empirical study confirm that a strategy based on the players' personal branding is rewarding and can increase both the follower base and the commitment to the team.

The immense regenerative power of hematopoietic tissue stems from the activation of the immature stem cells and the progenitor cells. After partial damage, hematopoiesis is reconstituted through a period of intense regeneration when blood cell production originates from erythro-myeloid progenitors in the virtual absence of stem cells. Since the damaged hematopoiesis can also be reconstituted from transplanted hematopoietic cells, we asked whether this also leads to the transient state when activated progenitors initially execute blood cell production. We first showed that the early reconstitution of hematopoiesis from transplanted cells gives rise to extended populations of developmentally advanced but altered progenitor cells, similar to those previously identified in the bone marrow regenerating from endogenous cells. We then identified the cells that give rise to these progenitors after transplantation as LSK CD48– cells. In the submyeloablative irradiated host mice, the transplanted LSK CD48– cells preferably colonized the spleen. Unlike the endogenous hematopoiesis reconstituting cells, the transplanted whole bone marrow cells and sorted LSK CD48– cells had greater potential to differentiate to B-lymphopoiesis. Separate transplantation of the CD150– and CD150+ subsets of LSK CD48– cells suggested that CD150– cells had a greater preference to B-lymphopoiesis than CD150+ cells. In the intensively regenerating hematopoiesis, the CD71/Sca-1 plot of immature murine hematopoietic cells revealed that the expanded populations of altered myeloid progenitors were highly variable in the different places of hematopoietic tissues. This high variability is likely caused by the heterogeneity of the hematopoiesis supporting stroma. Lastly, we demonstrate that during the period when active hematopoiesis resumes from transplanted cells, the hematopoietic tissues still remain highly permissive for further engraftment of transplanted cells, particularly the stem cells. Thus, these results provide a rationale for the transplantation of the hematopoietic stem cells in successive doses that could be used to boost the transplantation outcome.

The original version of this Article contained an error in the Acknowledgments section.

Abstract We calculate the m ϱ /f π ratio in the chiral and continuum limit for SU(3) gauge theory coupled to N f = 2, 3, 4, 5, 6 fermions in the fundamental representation. Keeping all systematic effects under full control we find no statistically significant N f -dependence; m ϱ /f π = 7.95(15). Assuming the KSRF-relations we conclude that 3 other low energy quantities related to the vector meson are also N f -independent within errors including the ϱππ coupling g ϱππ . If the model is thought of as a strong dynamics inspired composite Higgs model our results indicate that the experimentally most easily accessible new composite particle, the vector meson, and its properties may be robust and independent of the fermion content of the model as long as the gauge group is SU(3), provided N f -independence extends all the way to the conformal window.

Fenugreek is used as a spice and a traditional herbal medicine for a variety of purposes, given its antidiabetic and antioxidant effects. Self-emulsifying drug delivery systems (SEDDS) of herbal drugs are targets of extensive research aiming to increase bioavailability and stability. The study’s objective was to formulate SEDDS containing Trigonella foenum-graecum extract to improve the stability of herbal extract and to increase their permeability through a Caco-2 monolayer. A characterized fenugreek dry extract was used for the formulations, while the SEDDS properties were examined by particle size analysis and zeta potential measurements. Permeability assays were carried out on Caco-2 cell monolayers, the integrity of which was monitored by follow-up trans-epithelial electric resistance measurements (TEER). Cytocompatibility was tested by the MTT method, and an indirect dissolution test was performed, using DPPH antioxidant reagent. Two different SEDDS compositions were formulated from a standardized fenugreek dry extract at either the micro- or the nanoemulsion scale with sufficient stability, enhanced bioavailability of the compounds, and sustained release from HPMC capsules. Based on our results, a modern, non-toxic, cytocompatible fenugreek SEDDS formulation with high antioxidant capacity was developed in order to improve the permeability and bioavailability of all components.

Regeneration of severely damaged adult tissues is currently only partially understood. Hematopoietic tissue provides a unique opportunity to study tissue regeneration due to its well established steady-state structure and function, easy accessibility, well established research methods, and the well-defined embryonic, fetal, and adult stages of development. Embryonic/fetal liver hematopoiesis and adult hematopoiesis recovering from damage share the need to expand populations of progenitors and stem cells in parallel with increasing production of mature blood cells. In the present study, we analyzed adult hematopoiesis in mice subjected to a submyeloablative dose (6 Gy) of gamma radiation and targeted the period of regeneration characterized by massive production of mature blood cells along with ongoing expansion of immature hematopoietic cells. We uncovered significantly expanded populations of developmentally advanced erythroid and myeloid progenitors with significantly altered immunophenotype. Their population expansion does not require erythropoietin stimulation but requires the SCF/c-Kit receptor signaling. Regenerating hematopoiesis significantly differs from the expanding hematopoiesis in the fetal liver but we find some similarities between the regenerating hematopoiesis and the early embryonic definitive hematopoiesis. These are in (1) the concomitant population expansion of myeloid progenitors and increasing production of myeloid blood cells (2) performing these tasks despite the severely reduced transplantation capacity of the hematopoietic tissues, and (3) the expression of CD16/32 in most progenitors. Our data thus provide a novel insight into tissue regeneration by suggesting that cells other than stem cells and multipotent progenitors can be of fundamental importance for the rapid recovery of tissue function.

Abstract SU(2) gauge theory is investigated with a lattice action which is insensitive to small perturbations of the lattice gauge fields. Bare perturbation theory can not be defined for such actions at all. We compare non-perturbative continuum results with that obtained by the usual Wilson plaquette action. The compared observables span a wide range of interesting phenomena: zero temperature large volume behavior (topological susceptibility), finite temperature phase transition (critical exponents and critical temperature) and also the small volume regime (discrete β-function or step-scaling function). In the continuum limit perfect agreement is found indicating that universality holds for these topological lattice actions as well.

Abstract Background The health of plants is heavily influenced by the intensively researched plant microbiome. The microbiome has to cope with the plant’s defensive secondary metabolites to survive and develop, but studies that describe this interaction are rare. In the current study, we describe interactions of endophytic fungi with a widely researched chemical defense system, the glucosinolate - myrosinase - isothiocyanate system. The antifungal isothiocyanates are also of special interest because of their beneficial effects on human consumers. Results Seven endophytic fungi were isolated from horseradish roots (Armoracia rusticana), from the genera Fusarium, Macrophomina, Setophoma, Paraphoma and Oidiodendron. LC-ESI-MS analysis of the horseradish extract incubated with these fungi showed that six of seven strains could decompose different classes of glucosinolates. Aliphatic, aromatic, thiomethylalkyl and indolic glucosinolates were decomposed by different strains at different rates. SPME-GC-MS measurements showed that two strains released significant amounts of allyl isothiocyanate into the surrounding air, but allyl nitrile was not detected. The LC-ESI-MS analysis of many strains’ media showed the presence of allyl isothiocyanate - glutathione conjugate during the decomposition of sinigrin. Four endophytic strains also accepted sinigrin as the sole carbon source. Isothiocyanates inhibited the growth of fungi at various concentrations, phenylethyl isothiocyanate was more potent than allyl isothiocyanate (mean IC50 was 2.30-fold lower). As a control group, ten soil fungi from the same soil were used. They decomposed glucosinolates with lower overall efficiency: six of ten strains had insignificant or weak activities and only three could use sinigrin as a carbon source. The soil fungi also showed lower AITC tolerance in the growth inhibition assay: the median IC50 values were 0.1925 mM for endophytes and 0.0899 mM for soil fungi. Conclusions The host’s glucosinolates can be used by the tested endophytic fungi as nutrients or to gain competitive advantage over less tolerant species. These activities were much less apparent among the soil fungi. This suggests that the endophytes show adaptation to the host plant’s secondary metabolites and that host metabolite specific activities are enriched in the root microbiome. The results present background mechanisms enabling an understanding of how plants shape their microbiome.

Background: Cardioprotective effects of H2S are being suggested by numerous studies. Furthermore, H2S plays a role in relaxation of vascular smooth muscle, protects against oxidative stress, and modulates inflammation. Long-term high-dose use of NSAIDs, such as ibuprofen, have been associated with enhanced cardiovascular risk. The goal of the present work is the synthesis and basic pharmacological characterization of a newly designed H2S-releasing ibuprofen derivative. Methods: Following the synthesis of EV-34, a new H2S-releasing derivative of ibuprofen, oxidative stability assays were performed (Fenton and porphyrin assays). Furthermore, stability of the molecule was studied in rat serum and liver lysates. H2S-releasing ability of the EC-34 was studied with a hydrogen sulfide sensor. MTT (3-(4,5-dimethylthiazol 2-yl)-2,5-(diphenyltetrazolium bromide)) assay was carried out to monitor the possible cytotoxic effect of the compound. Cyclooxygenase (COX) inhibitory property of EV-34 was also evaluated. Carrageenan assay was carried out to compare the anti-inflammatory effect of EV-34 to ibuprofen in rat paws. Results: The results revealed that the molecule is stable under oxidative condition of Fenton reaction. However, EV-34 undergoes biodegradation in rat serum and liver lysates. In cell culture medium H2S is being released from EV-34. No cytotoxic effect was observed at concentrations of 10, 100, 500 µM. The COX-1 and COX-2 inhibitory effects of the molecule are comparable to those of ibuprofen. Furthermore, based on the carrageenan assay, EV-34 exhibits the same anti-inflammatory effect to that of equimolar amount of ibuprofen (100 mg/bwkg). Conclusion: The results indicate that EV-34 is a safe H2S releasing ibuprofen derivative bearing anti-inflammatory properties.

Mutations in the splicing factor 3b subunit 1 (SF3B1) gene are frequent in myelodysplastic neoplasms (MDS). Because the splicing process is involved in the production of circular RNAs (circRNAs), we investigated the impact of SF3B1 mutations on circRNA processing. Using RNA sequencing, we measured circRNA expression in CD34+ bone marrow MDS cells. We defined circRNAs deregulated in a heterogeneous group of MDS patients and described increased circRNA formation in higher‐risk MDS. We showed that the presence of SF3B1 mutations did not affect the global production of circRNAs; however, deregulation of specific circRNAs was observed. Particularly, we demonstrated that strong upregulation of circRNAs processed from the zinc finger E‐box binding homeobox 1 (ZEB1) transcription factor; this upregulation was exclusive to SF3B1‐mutated patients and was not observed in those with mutations in other splicing factors or other recurrently mutated genes, or with other clinical variables. Furthermore, we focused on the most upregulated ZEB1‐circRNA, hsa_circ_0000228, and, by its knockdown, we demonstrated that its expression is related to mitochondrial activity. Using microRNA analyses, we proposed miR‐1248 as a direct target of hsa_circ_0000228. To conclude, we demonstrated that mutated SF3B1 leads to deregulation of ZEB1‐circRNAs, potentially contributing to the defects in mitochondrial metabolism observed in SF3B1‐mutated MDS. [ABSTRACT FROM AUTHOR]