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Adult stem cells are responsible for homoeostasis and regeneration of epithelial tissues. Stem cell function is regulated by both cell autonomous mechanisms as well as the niche. Deregulated stem cell function contributes to diseases such as cancer. Epithelial organoid cultures generated from tissue-resident adult stem cells have allowed unprecedented insights into the biology of epithelial tissues. The subsequent adaptation of organoid technology enabled the modelling of the communication of stem cells with their cellular and non-cellular niche as well as diseases. Starting from its first model described in 2009, the murine small intestinal organoid, we discuss here how epithelial organoid cultures have been become a prime in vitro research tool for cell and developmental biology, bioengineering, and biomedicine in the last decade.

A significant part of the world's population lives around rivers. The riparian zone is not only a source of drinking water for urbanised areas; streams and rivers are also sinks for wastewater. As a result of the increased consumption of pharmaceutically active compounds (PhACs) in past decades, wastewater untreated and treated is a continuous load of these compounds (and their metabolites) to fluvial systems. The water supply for these kinds of urbanised areas is partly provided by riverbank filtration plants which can be significantly affected by PhACs loading. Riverbank filtration is effective for most pollutants. However, the filtering efficiency for these molecules is poorly known. This presentation focuses on the spatial and temporal distribution of more than a hundred PhACs in the streams and rivers of the Budapest Metropolitan Area. Our presentation demonstrates that bank filtration can also be effective for the filtration of organic micro-pollutants in highly urbanised areas.Samples were collected during five sampling campaigns. The streams, rivers, and drinking water wells were sampled. The stream sediments were also sampled. Altogether 111 PhACs were measured. In small streams and rivers, eighty-one PhACs were systematically detected, while fifty-three PhACs were detected in the Danube. The quantification of 19 PhACs in the Budapest section of the river was without any precedent, and 10 PhACs were present in >80% of the samples. More PhACswere detectable in the small watercourses, and the concentrations were significantly higher than in the Danube. Sediments always contain fewer PhACs than water. This is mainly due to the high sorption capacity of sediments.The most frequent PhACs showed higher concentrations in winter than in summer. In the drinking water wells 32 PhACs were quantified. For the majority of PhACs, the bank filtration efficiency was higher than 95%. Concentrations of the compounds did not influence the efficiency of filtering. For some PhACs (e.g. carbamazepine lidocaine, tramadol, and lamotrigine), low filtration efficiency was observed. These frequently occurring PhACs in surface waters have a relatively even distribution, and their sporadic appearance in wells is a function of both space and time, which may be caused by the constantly changing environment and micro-biological parameters, the dynamic operating schedule of abstraction wells, and the resulting sudden changes in flow rates.This research was funded by the National Research, Development, and Innovation Office (NKFIH), grant numbers: K-142865 and 2020-1.1.2-PIACI-KFI-2021-00309.

The ever-increasing use of pharmaceuticals in the 21st century has led to growing concern about the environmental impact of pharmaceutical substances. In terms of their mechanism of action, antibiotics pose one of the most significant risks to the environment by altering microbiological conditions. Microbial degradation of organic matter in soil systems is the primary driver of the carbon cycle, so antibiotic pollution can significantly impact soil CO2 emissions. Soil organic matter is not a homogenous system; most soil organic carbon models separate different carbon pools with shorter and longer decomposition times. As previously published, different soil organic carbon pools may have different chemical properties, and therefore adsorption properties. This study focused on the adsorption properties of different soil carbon fractions.Adsorption studies were performed on three fluoroquinolone antibiotics (ciprofloxacin, norfloxacin, ofloxacin) by batch and kinetic experiments on three Luvisol samples with different land use (arable, grassland, forest). The SOM fractionation was based on the Zimmermann procedure, and the batch and kinetic experiments have also been carried out on the fractions. The soil fractions were analysed by TOC, XRD, XRF, BET, FTIR during the adsorption. Langmuir and Freundlich models were applied on the equilibrium data. The kinetics data were analysed by pseudo-first and second-order kinetics models. The main parameters affecting adsorption were studied by principal component analysis. Our results suggest that the long-term carbon pools are most affected by the adsorption of antibiotics. PREPARED WITH THE PROFESSIONAL SUPPORT OF THE DOCTORAL STUDENT SCHOLARSHIP PROGRAM OF THE CO-OPERATIVE DOCTORAL PROGRAM OF THE MINISTRY OF INNOVATION AND TECHNOLOGY FINANCED FROM THE NATIONAL RESEARCH, DEVELOPMENT AND INNOVATION FUND.

Wastewater treatment technologies worldwide use only marginally reduce the number of organic micropollutants (e.g. pharmaceuticals) in treated wastewater. Treated wastewater is used for irrigation in semi-arid and Mediterranean areas. Most of the treated wastewater is discharged into surface water bodies In European Countries. The use of these water bodies for irrigation results in the presence of PhACs into the agro-environment. The ever-changing environment in the soils influences the adsorption of these compounds. One of the ever-changing environmental factors is pH. The pH can highly fluctuate in the rhizosphere during the whole growing season. Consequently, the study of the effect of this environmental factor should also be considered when assessing the environmental risk of PhACs.The main questions of our research were: (a) How do root acids affect adsorption-desorption interactions?; (b) Are there synergistic effects during competitive adsorption of 17α-ethinyl estradiol (EE2), carbamazepine (CBZ), and diclofenac sodium (DFC)?Studied compounds were tested in both single-compound adsorption and competitive adsorption and batch experiments. The adsorbents were from a calcareous, humic sandy soil used to grow lucerne. The sorption experiments were carried out at three different depths of the soil profile, where at the ploughed layer (0-20 cm), soil pH was adjusted to model the effect of ambient acids on sorption processes. Competitive adsorption tests were performed at both the original and the modified pH values. Adsorption isotherms were applied to estimate the model parameters using Langmuir, Freundlich, and Dubinin-Radushkevich model. According to our results, the pH changes influenced the sorption processes, especially the desorption. The outcome of our study could be able to estimate the behaviour of PhACs at different soil horizons of sandy agricultural soil.This study was funded by the Hungarian National Research, Development, and Innovation Fund (2020-1.1.2-PIACI-KFI-2021-00309).

The fate of Pharmaceutically Active Compounds (PhACs) in the environment may depend on a number of interrelated processes. Their environmental risk is mainly influenced by their adsorption and desorption processes in the soil. The present work aimed to study the adsorption and desorption of PhACs (17α-ethinyl estradiol (EE2), carbamazepine (CBZ), diclofenac sodium (DFC)) on various agricultural soils formed under different redox conditions: an Arenosol with fully aerobic conditions and a Histic Gleysol sample with suboxic and anoxic conditions. The objectives of the study were to investigate how the soil properties modify the sorption processes of the PhACs. Adsorption isotherms were applied to estimate the model parameters using Langmuir, Freundlich and Dubinin-Radushkevich model in a batch technique experiment. The different composition of the soil samples significantly affected the amount of adsorbed PhACs (CBZ, DFC, EE2). Top soil samples with a high organic matter content adsorbed higher amounts of PhACs, while the amount of adsorbed PhACs decreased gradually with depth. In desorption experiments, the amount of PhACs released also varied with depth. In contrast, the rate of desorption was lowest at the topsoil samples and increased with depth. In samples where the deeper levels were characterised by higher clay mineral content (e.g. the C-level of the Histic Gleysol), significantly less PhACs could be desorbed. The physico-chemical properties of the soil showed that the amount of the desorbed PhACs mainly influenced by the specific surface area and clay content of the soil. This study could be useful for understanding of the movement of PhACs in soils formed under different conditions. This study was funded by the Hungarian National Research, Development and Innovation Fund (2020-1.1.2-PIACI-KFI-2021-00309).

Small streams are crucial but vulnerable elements of ecological networks. To better understand the occurrence of pharmaceutically active compounds (PhACs) in streams, this study focused on the occurrence, distribution, and environmental risk of 111 PhACs and 7 trace elements based on a total of 141 water and sediment samples from small streams located in the urbanizing region of Budapest, Hungary. Eighty-one PhACs were detected in the aqueous phase, whereas sixty-two compounds were detected in the sediment. Carbamazepine (CBZ) was the most frequently identified PhAC in water, and was found in 91.5% of all samples. However, the highest concentrations were measured for lamotrigine (344.8 μg·L

Despite the fact that there are tens of thousands of thermal baths in existence, knowledge about the occurrence of pharmaceutically active compounds (PhACs) in untreated thermal wastewater is very limited. Because used thermal water is typically legally discharged into surface waters without any treatment, the effluent poses environmental risks for the receiving water bodies. The aim of this study was to show the occurrence patterns and spatiotemporal characteristics of 111 PhACs in thermal wastewater. Six thermal water outflows of different thermal baths were tested in different seasons in the Budapest metropolitan region (Hungary), and diurnal analysis was performed. After solid-phase extraction, the samples were analysed and quantified by coupling supercritical fluid chromatography and mass spectrometry to perform simultaneous multi-residue drug analysis. The results confirm that water discharge pipes directly transport pharmaceuticals into surface water bodies; 34 PhACs were measured to be over the limit of quantification at least once, and 21 of them were found in more than one water sample. The local anaesthetic drug lidocaine, antiepileptic carbamazepine, analgesic derivative tramadol and illicit drug cocaine were detected in more than half of the samples. Caffeine, metoprolol and bisoprolol (cardiovascular drugs), benzoylecgonine (cocaine metabolite), diclofenac (NSAID), citalopram (antidepressant) and certain types of hormones also have a significant frequency of 30-50%. However, the occurrence and concentrations of PhACs vary according to the season and number/types of visitors. As demonstrated by the diurnal fluctuation, drug contamination of thermal waters can significantly vary, even for similar types of baths; furthermore, the quantity and types of some pollutants rapidly change in the discharged thermal wastewater. Electronic supplementary material The online version of this article (10.1007/s11356-019-06633-6) contains supplementary material, which is available to authorized users.

Extracellular vesicles (EVs) are membrane-surrounded structures that transmit biologically important molecules from the releasing to target cells, thus providing a novel intercellular communication mechanism. Since EVs carry their cargo in a protected form and their secretion is generally increased in tumorigenesis, EVs hold a great potential for early cancer diagnosis. By 3D culturing, we provide evidence that colorectal cancer (CRC) patient-derived organoids, representing a state-of-the-art established and essential approach for studying human CRC, is a suitable model for EV analysis. When testing the effects of major factors promoting CRC progression on EV release in the organoid model, we observed that Apc mutation, leading to uncontrolled Wnt activation and thus to tumorigenesis in the vast majority in CRC patients, critically induces EV release by activating the Wnt pathway. Furthermore, the extracellular matrix component collagen, known to accumulate in tumorigenesis, enhances EV secretion as well. Importantly, we show that fibroblast-derived EVs induce colony formation of CRC organoid cells under hypoxia. In contrast, there was no major effect of tumor cell-derived EVs on the activation of fibroblasts. Collectively, our results with CRC and Apc-mutant adenoma organoids identify Apc mutation and collagen deposition as critical factors for increasing EV release from tumors. Furthermore, we provide evidence that stromal fibroblast-derived EVs contribute to tumorigenesis under unfavorable conditions in CRC. Electronic supplementary material The online version of this article (10.1007/s00018-019-03052-1) contains supplementary material, which is available to authorized users.

The role of the chemical properties of Pharmaceutically Active Compounds (PhACs) in their sorption behaviour and consequently in their fate and mobility is of major environmental interest, but a comprehensive evaluation is still lacking. The sorption of nine PhAC molecules with distinct physico-chemical properties on soils and goethite was described using linear, Freundlich and Langmuir models and the relationship between the chemical structures of the compounds and the parameters of the adsorption was evaluated using redundancy analysis (RDA). The latter showed that the sorption of the pharmaceuticals was determined by the intrinsic chemical characteristics of the molecules, as shown by the 35% value of constrained variability. For the hydrophobic estrogens, E1, E2 and EE2, the logD value and the number of hydrogen bond sites were found to be the main controlling factors for adsorption, indicating that hydrophobic interaction and hydrogen bonding are the dominant sorption mechanisms. The π energy of the molecules also proved a very important parameter, governing the retention of PhACs in soils, especially in the case of carbamazepine, oxazepam and lamotrigine. The main controlling factor for ionic compounds, such as diclofenac sodium, tramadol or lidocaine, is the fraction of PhACs present as charged species, revealing the importance of Coulomb forces. The results of this study will allow semi-quantitative predictions to be made on how the molecular structure governs the sorption of PhACs and which sorption mechanism could be involved.

Laser diffraction grain size data have been widely used in paleoenvironmental reconstructions as physicochemical alteration-related proxies. Many studies are available on comparison of different laser diffraction devices, optical theories and optical settings. The ignorance of some uncertainty factors can lead to poorly comparable granulometric datasets. Other important factor leading to the aforementioned effect is the inadequate chemical pretreatment procedures which are often overlooked, but are capable to basically affect the results. In this study we examine a few past and recent sediment types from different geomorphological environments from the Carpathian Basin: lake and fluvial sediments, paleosols and loess. Our aim is to review and create a reliable methodology for laser diffraction particle size analysis and optical particle shape investigations. We compare widely used pretreatment methods -which can be found in the literature- with each other. We are also taking into account that different sediment types need different pretreatment methods. We can state that the duration of chemical pretreatment can affect the optical properties (color), the texture and the mineral composition of the sediments, as well as the size and shape of mineral particles in the samples. The changes in these significant parameters can mislead the researcher’s main objectives. The study is supported by the ÚNKP-19-3 New National Excellence Program of the Ministry for Innovation and Technology. Support of the National Research, Development and Innovation Office NKFIH K120620 is gratefully acknowledged.

The top metre of the soil is one of the largest terrestrial carbon reservoirs. More than 50% of the soil carbon is stored as soil organic matter (SOM). Several papers report about the SOM losses due to tillage and land-use change. On the other hand, a huge amount of papers focus on the environmental potential of various min-till, no-till and other techniques for regenerative agriculture. The change of the fertilization regime also has an influence on SOM so it also can influence the humus status of the soils. This presentation focuses on the effects of different kinds of fertilization and abandonment of arable lands on the quantity and quality of the SOM.The present study is based on Martonvásár Experimental Station (Hungary) which was established in 1958. The research focused on maize monoculture with the following treatments: (a) no fertilization, (b) NPK, (c) NPK with manure addition. The soil of the plots is Chernozem. Two controls were selected: (a) a natural Grassland and a secondary grassland. The secondary grassland was an arable land until 1990. Five repetitions of soil samples were taken from each plot and times. Soils were fractionated to silt and clay associated OM (s+c), aggregate associated OM (S+A), dissolved organic matter (DOM) and particulate organic matter (POM) according to Zimmermann’s method (4). Quality parameters of the DOM were studied by CN analyser, UV-Vis spectrometer, spectrofluorometer, zetasizer and size exclusion chromatograph. Solid SOM fractions were studied by CHNS analyser, ATR-FTIR and DRIFT FTIR. The V3-V4 regions of the 16S rRNA gene obtained from the soil samples were sequenced on the Illuma platform for the description of microbial diversity.Twenty years were enough to restore the natural SOM content of the soils (land-use change from arable land to grassland). Labile fractions of the SOM were higher in case of secondary than the primary grasslands. We have found differences in weight ratios of SOM fractions between fertilization regimes, as well. The proportion of microbial contribution to SOM were higher in the arable soils than the grasslands based on the C:N ratios of the SOM. However, the predominance of phyla Proteobacteria, Acidobacteria, Bacteriodetes, Actinobacteria and Verrucomicrobia in all studied soils, microbial diversity is generally higher in the grasslands than in the arable plots. The DOM of different fertilization regimes and land uses have shown the most characteristic differences. The difference between arable plots (with various fertilization regimes) and grasslands can be characterized by humic substances (HS) with higher condensation degree and molecular mass. The application of manure has result same proportion of peptide-like components and HS with lower molecular as the DOM of grassland soils.The microbial diversity of abandoned arable land remained similar to that of the arable lands over twenty years. The major part of the growth of SOM occurred in the labile fractions. The change of the fertilization regime also has limited potential to grow a total mass of SOM.Support of the GINOP 2.3.2-15-2016-00056 and National Research, Development and Innovation Office under contracts K123953 are gratefully acknowledged.

Pedogenesis is considered a long-term environmental process; however, it can be accelerated by periodic water saturation (hydric conditions). The exact nature and effectiveness of hydric conditions in the intensification of soil development are not clear yet. Our understanding of the timescales of the mineralogical changes occurring in soils is limited; however, the timeframe of soil organic matter accumulation is broadly known. Here, we described soil development over a period of 50 years. The studied soils Calcaric Mollic Gleysol (Endoarenic, Epiloamic, Hyperhumic) and a Calcaric Calcic Histic Gleysol (Endoarenic, Epiloamic) are located in a swampy area in Hungary, Central Europe. The start of the soil formation process is well documented here; the parent material was deposited during a major flood event in 1963. Therefore, the examined soil profile represents development over the last 50 years. We also studied the parent material of an adjacent dune as a reference. We used a CN elemental analyser to determine soil organic carbon and total bound nitrogen content. Selective extractions were also used to determine amorphous and crystalline Fe and Mn content alongside X-ray phase analysis (XRD) and transmission electron microscopy (TEM) for mineralogical analysis, X-ray fluorescence spectroscopy (XRF) for elemental analysis, and laser diffraction for particle size analysis of the bulk soil samples. Simple chemical tests were also performed in the field. Redox potential (Eh) and pH were measured by a field monitoring station. Fifty years under hydric conditions resulted in rapid vertical differentiation within the soil profile including remarkable soil organic matter enrichment in the topsoil, and the formation of smectite and Fe accumulation in the zone of groundwater fluctuation. A high proportion of amorphous and colloidal phases indicated that very intense processes had taken place in the zone of the most intensive redox oscillation. The presence of more crystalline goethite in the bulk soil reflects frequent Eh changes, associated with chemical or microbial processes, while the presence of amorphous ferrihydrite indicates the effect of plant roots. Permanently reductive subsoil conditions also facilitated intense carbonate precipitation. These findings demonstrate that soil formation can proceed faster than previously assumed under hydric conditions.

Cross metatheses of tung oil, a nonedible vegetable oil and α-eleostearic acid ((9Z,11E,13E)-octadeca-9,11,13-trienoic acid, ESA) methyl ester (1), obtained from tung oil containing the same highly unsaturated, conjugated double bonds, have been carried out with cis-1,4-diacetoxy-2-butene (2) using Hoveyda-Grubbs (3-HG2) or Grubbs second or third generation catalysts (3-G2 or 3-G3). The reactions followed by Pd/C-catalyzed hydrogenation give methyl 11-acetoxyundecanoate (4) as a polyester raw material, 1,6-diacetoxy-hexane (5) as a precursor of 1,6-hexanediol (6) polyurethane monomer, and heptyl acetate as a fragrance (7) in 53–99% yields after Pd/C-catalyzed hydrogenation. The one-pot isomerization metathesis of α-linolenic acid ((9Z,12Z,15Z)-9,12,15-octadecatrienoic acid, ALA) methyl ester (7) using 2 as cross coupling agent, RuHCl(CO)(PPh3)3 (9) as isomerization, and 3-G2 as a metathesis catalyst followed by Pd/C catalyzed hydrogenation leads also to the formation of 5 and the homologues of 4 and 7 in ...

The presence of pharmaceutically active compounds (PhACs) in drinking waters might pose a serious threat to human health worldwide. Therefore, this study sought to measure PhACs in Danube-derived tap water from the Budapest metropolitan region (Hungary), and to compare the results of those measured in the bank filtrate after which a human health risk assessment (based on human risk quotient [hRQ]) was conducted for the detected PhACs. A total of 108 samples were collected from 21 sampling sites throughout 6 sampling campaigns. Our study screened for 102 PhACs, of which 19 were detected in the persistently chlorinated tap water samples. PhAC concentrations were much lower than previously assumed based on the contamination of raw water resources. The total mean concentration of the analyzed PhACs exceeded 30 ng L−1 only at 5 sites. Moreover, the frequency of occurrence (FRO) of the 6 most common compounds (carbamazepine, lamotrigine, lidocaine, benzoylecgonine, tramadol, and cinolazepam) reached 50 % at 4 sites. The most frequent PhAC was carbamazepine (FRO = 53.7 %), the risk level of all PhACs investigated was negligible (hRQ

Surface waters are becoming increasingly contaminated by pharmaceutically active compounds (PhACs), which is a potential risk factor for drinking water quality owing to incomplete riverbank filtration. This study examined the efficiency of riverbank filtration with regard to 111 PhACs in a highly urbanized section of the river Danube. One hundred seven samples from the Danube were compared to 90 water samples from relevant drinking water abstraction wells (DWAW) during five sampling periods. The presence of 52 PhACs was detected in the Danube, the quantification of 19 agents in this section of the river was without any precedent, and 10 PhACs were present in80% of the samples. The most frequent PhACs showed higher concentrations in winter than in summer. In the DWAWs, 32 PhACs were quantified. For the majority of PhACs, the bank filtration efficiency was95%, and not influenced by concentrations measured in the river. For carbamazepine lidocaine, tramadol, and lamotrigine, low (50%) filtration efficiency was observed; however, no correlations were observed between the concentrations detected in the Danube and in the wells. These frequently occurring PhACs in surface waters have a relatively even distribution, and their sporadic appearance in wells is a function of both space and time, which may be caused by the constantly changing environment and micro-biological parameters, the dynamic operating schedule of abstraction wells, and the resulting sudden changes in flow rates. Due to the changes in the efficiency of riverbank filtration in space and time, predicting the occurrence and concentrations of these four PhACs poses a further challenge to ensuring a safe drinking water supply.

A study was conducted on the sorption of 17α-ethynylestradiol (EE2) on five soils formed under different redox conditions: an Arenosol (A_20) with fully aerobic conditions, two Gleysol samples (G_20 and G_40) with suboxic and anoxic conditions and two Histosols (H_20 and H_80) with mostly anoxic conditions. The soils were characterized on the basis of total organic carbon (TOC), specific surface area (SSA) and the Fourier transform infrared spectra of the humic acid and humin fractions (the soil remaining after alkali extraction) of the soil. The maximum adsorption capacity of the soils (Qmax) ranged from 10.7 to 83.6 mg/g in the order G_20 > H_20 > G_40 > A_20 > H_80, which reflected the organic matter content of the soils. The sorption isotherms were found to be nonlinear for all the soil samples, with Freundlich n values of 0.45–0.68. The strong nonlinearity found in the adsorption of the H_80 samples could be attributed to their high hard carbon content, which was confirmed by the high aromaticity of the humin fraction. The maximum sorption capacity (Qmax) of the soils did not increase indefinitely as the organic carbon content of the soils rose. There could be two reasons for this: (i) the large amount of organic matter may reduce the number of binding sites on the surface, and (ii) the decrease in SSA with increasing soil OC content may limit the ability to adsorb EE2 molecules. In anaerobic soil samples, where organic matter accumulation is pronounced, the amount of aromatic and phenolic compounds was higher than in better aerated soil profiles. Strong correlations were found between the amount of aromatic and phenolic compounds in the organic matter and the adsorption of EE2 molecules, indicating that π-π interaction and H-bonding are the dominant sorption mechanisms.

A large vocabulary continuous speech recognition (LVCSR) system designed for dictation of medieval Latin language documents is introduced. Such language technology tool can be of great help for preserving Latin language charters from this era, as optical character recognition systems are often challenged by these historical materials. As corresponding historical research focuses on the Visegrad region, our primary aim is to make medieval Latin dictation available for texts and speakers of this region, concentrating on Czech, Hungarian and Polish. The baseline acoustic models we start with are monolingual grapheme-based ones. On one hand, the application of medieval Latin knowledge-based grapheme-to-phoneme (G2P) mapping from the source language to the target language resulted in significant improvement, reducing the Word Error Rate (WER) by \(13.3\%\). On the other hand, applying a Unified Simplified Grapheme (USG) inventory set for the three-language acoustic data set complemented with Romanian speech data, resulted in a further \(0.7\%\) WER reduction - without using any target or source language G2P rules.