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Novel soil datasets and the application of pedotransfer functions provide soil hydraulic input data for modelling hydrological processes at different scales. We aimed to evaluate the reliability of soil hydraulic parameters derived by indirect methods in simulation of soil moisture time series and water budgets at profile level of three sites (Forest, Orchard and Grassland) from a Central European catchment (Lake Balaton, Hungary). Five soil-vegetation-atmosphere model variants were set up with the Hydrus-1D model for each site, differing only in the parametrization of input soil data: i) a calibrated reference, ii) measured values, iii) values predicted from measured basic soil properties, iv) values predicted from national soil map information, v) values derived from the 3D soil hydraulic dataset of Europe. Calibrated soil parameters led to Nash-Sutcliffe efficiency 0.50, 0.54 and 0.71 for the Forest, Orchard and Grassland Site respectively. The outcomes for model efficiency of soil moisture underline the superiority of local databases over regional ones and the need for more detailed vertical discretization during modelling. The model performance according to soil moisture and water budget accuracy led to different rank order of model variants. Water budget comparisons indicated moderate differences between the hydrologic fluxes simulated by the different model variants, emphasizing the uncertainties associated with soil hydraulic parametrization either at local or at watershed scale.

Background: Building extensive drug candidate libraries as early in the development pipeline as possible, with high-throughput in vitro absorption, distribution, metabolism, and excretion (ADME) profiling, is crucial for the selection of lead compounds to guide subsequent research and production phases. Traditionally, the analysis of metabolic stability assays heavily relies on high-throughput LC-MS/MS (liquid chromatography tandem mass spectrometry) techniques to meet with the lead profiling demands. Laser-assisted rapid evaporative ionization mass spectrometry (LA-REIMS) is a quick and efficient technique for characterizing complex biological samples without laborious sample preparation. Objective: In this study, using an automated LA-REIMS well plate reader, achieving an 8 s per sample measurement time, the oxidative metabolic stability of active drug agents was assessed using biomimetic metalloporphyrin-based oxidative model reactions. Results: The results obtained using the novel LA-REIMS-based protocol were compared to and corroborated by those obtained using conventional HPLC-UV-MS (high performance liquid chromatography with ultra-violet detection coupled with mass spectrometry) measurements. Conclusions: LA-REIMS emerges as a promising technique, demonstrating potential suitability for semi-quantitative high-throughput metabolic stability in an optimized solvent environment.

Human tyrosine hydroxylase (hTH) has key role in the production of catecholamine neurotransmitters. The structure, function and regulation of hTH has been extensively researched area and the possibility of enzyme replacement therapy (ERT) involving hTH through nanocarriers has been raised as well. However, our understanding on how hTH may interact with nanocarriers is still lacking. In this work, we attempted to investigate the immobilization of hTH on magnetic nanoparticles (MNPs) with various surface linkers in quantitative and mechanistic detail. Our results showed that the activity of hTH was retained after immobilization via secondary and covalent interactions as well. The colloidal stability of hTH could be also enhanced proved by Dynamic light scattering and Zeta potential analysis and a homogenous enzyme layer could be achieved, which was investigated by Raman mapping. The covalent attachment of hTH on MNPs via aldehyde or epoxy linkers provide irreversible immobilization and 38.1 % and 16.5 % recovery (ER). The hTH-MNPs catalyst had 25 % ER in average in simulated nasal electrolyte solution (SNES). This outcome highlights the relevance of immobilization applying MNPs as a potential formulation tool of sensitive therapeutic enzymes offering new opportunities for ERT related to neurodegenerative disorders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The application of enzyme-based therapies has received significant attention in modern drug development. Lipases are one of the most versatile enzymes that can be used as therapeutic agents in basic skin care and medical treatment related to excessive sebum production, acne, and inflammation. The traditional formulations available for skin treatment, such as creams, ointments or gels, are widely applied; however, their use is not always accompanied by good drug penetration properties, stability, or patient adherence. Nanoformulated drugs offer the possibility of combining enzymatic and small molecule formulations, making them a new and exciting alternative in this field. In this study polymeric nanofibrous matrices made of polyvinylpyrrolidone and polylactic acid were developed, entrapping lipases from Candida rugosa and Rizomucor miehei and antibiotic compound nadifloxacin. The effect of the type of polymers and lipases were investigated, and the nanofiber formation process was optimized to provide a promising alternative in topical treatment. Our experiments have shown that entrapment by electrospinning induced two orders of magnitude increase in the specific enzyme activity of lipases. Permeability investigations indicated that all lipase-loaded nanofibrous masks were capable of delivering nadifloxacin to the human epidermis, confirming the viability of electrospinning as a formulation method for topical skin medications.

The investigation of liver-related metabolic stability of a drug candidate is a widely used key strategy in early-stage drug discovery. Metalloporphyrin-based biomimetic catalysts are good and well-described models of the function of CyP450 in hepatocytes. In this research, the immobilization of an iron porphyrin was performed on nanoporous silica particles via ionic interactions. The effect of the metalloporphyrin binding linkers was investigated on the catalytic efficiency and the metabolic profile of chloroquine as a model drug. The length of the amino-substituted linkers affects the chloroquine conversion as well as the ratio of human major and minor metabolites. While testing the immobilized catalysts in the continuous-flow reactor, results showed that the presented biomimetic system could be a promising alternative for the early-stage investigation of drug metabolites regarding analytical or synthetic goals as well.

Riverine floods cause increasingly severe damages to human settlements and infrastructure. Ecosystems have a natural capacity to decrease both severity and frequency of floods. Natural flood regulation processes along freshwaters can be attributed to two different mechanisms: flood prevention that takes place in the whole catchment and flood mitigation once the water has accumulated in the stream. These flood regulating mechanisms are not consistently recognized in major ecosystem service (ES) classifications. For a balanced landscape management, it is important to assess the ES flood regulation so that it can account for the different processes at the relevant sites. We reviewed literature, classified them according to these mechanisms, and analysed the influencing ecosystem characteristics. For prevention, vegetation biomass and forest extent were predominant, while for mitigation, the available space for water was decisive. We add some aspects on assessing flood regulation as ES, and suggest also to include flood hazard into calculations., (© 2022. The Author(s).)

Maintaining and, where possible, improving the ecological status of our water resources are of particular importance for the future. So, one of the main drivers of landscape design must be to protect our waters. In this study, we carried out an evaluation of four hydrologic ecosystem services (HES) in the Zala River catchment area, the largest tributary of Lake Balaton (more than half of the lake's surface inflow comes from the Zala River), Hungary. The lake has great ecological, economic and social importance to the country. We used the cell-based InVEST model to quantify the spatial distribution of flood control, erosion control and nutrient retention ecosystem services for phosphorus and nitrogen; then, we carried out an aggregated evaluation. Thereby, we localized the hot spots of service delivery and tested the effect of focused land use changes in critical areas of low performance on the examined four HES. Forests proved to have the best aggregated result, while croplands near the stream network performed poorly. The modelled change in land use resulted in significant improvement on nutrient filtration and moderate to minimal but improving change for the other HES in most cases. The applied method is suitable as a supporting tool at the watershed level for decision-makers and landscape designers with the aim of protecting water bodies., (© 2020. The Author(s).)

The dual functionalization of magnetic nanoparticles with inert (methyl) and reactive (aminopropyl) groups enables efficient immobilization of synthetic metalloporphyrins (such as 5,10,15,20-tetrakis(2,3,4,5,6-pentafluorophenyl)iron(II) porphyrin and 5,10,15,20-tetrakis-(4-sulfonatophenyl)iron(II) porphyrin) via covalent or ionic interactions. The proportion of reactive function on the surface has significant effect on the biomimetic activity of metalloporphyrins. The optimized magnetic nanocatalyst containing porphyrin was successfully applied for biomimetic oxidation of antihypertensive drug Amlodipine in batch and continuous-flow reactors as well.

Groundwater (GW) in many regions is essential for agricultural productivity, especially during drought periods. The shrinking of GW is an important but rarely documented component of the recent global environmental crisis and may threaten food security. The problem cannot be put in proper perspective, because we rarely have datasets long and detailed enough to scrutinise the unfolding effects at regional scales. To address this knowledge gap, we used a 50-y long (1961-2010) and spatially extensive (283 GW wells) dataset from Hungary to examine the GW trends and the sensitivity of the yields of two important crops to GW fluctuations. During 1986-2010, GW levels were significantly (0.21-0.60 m) lower than during 1961-1985 in every region of Hungary and every month of the year. The decrease was 2.24 cm y -1 at the country level. Linear and bootstrap resampling tests indicated weak relationship between GW levels and wheat yields but decreasing GW levels accounted for 18-38% of maize yield variability during the 'climate change affected' period of 1986-2010. Calculating the impact of GW on potential food production, a 100 mm higher GW levels would have increased annual maize yields by 0.23 t ha -1 on the Hungarian Plain. However, the registered GW decrease caused an estimated maize yield loss of 0.65 t ha -1 , i.e. 11.6% of the average annual yield during 1986-2010. GW level fluctuations on the plain showed a significant correlation with August-October soil moisture gridded data over much of the agricultural landscapes of Central and Western Europe, indicating a similar situation in a wider European context. To mitigate the cumulative negative impact of GW decrease and the rising temperature, GW recharge via infiltration of retained water would be an adequate solution. Areas of former floodplains with low agroecological suitability, amounting to almost a quarter of the Hungarian Plain could serve as such water retention areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Biomimetic oxidation of drugs catalyzed by metalloporphyrins can be a novel and promising way for the effective and sustainable synthesis of drug metabolites. The immobilization of 5,10,15,20-tetrakis(2,3,4,5,6-pentafluorophenyl)iron(II) porphyrin (FeTPFP) and 5,10,15,20-tetrakis-(4-sulfonatophenyl)iron(II) porphyrin (FeTSPP) via stable covalent or rapid ionic binding on aminopropyl-functionalized magnetic nanoparticles (MNPs-NH 2 ) were developed. These immobilized catalysts could be efficiently applied for the synthesis of new pharmaceutically active derivatives and liver related phase I oxidative major metabolite of an antiarrhythmic drug, amiodarone integrated in a continuous-flow magnetic chip reactor (Magnechip)., Competing Interests: The authors declare no conflict of interest.

A medium-throughput screening (MTS) of biomimetic drug metabolite synthesis is developed by using an iron porphyrin catalyst. The microplate method, in combination with HPLC-MS analysis, was shown to be a useful tool for process development and parameter optimization in the production of targeted metabolites and/or oxidation products of forty-three different drug substances. In the case of the biomimetic oxidation of amiodarone, the high quantity and purity of the isolated products enabled detailed HRMS and NMR spectroscopic studies. In addition to identification of known metabolites, several new oxidation products of the drug that was studied were characterized. Fast degradation and poor recovery of the catalyst under batch conditions was overcome by immobilization of 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin iron(III) chloride (FeTSPP) on the surface of 3-aminopropyl-functionalized silica by electrostatic interaction. The supported catalyst was successfully applied in a packed-bed reactor under continuous-flow reaction conditions for the large-scale synthesis of amiodarone metabolites., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)