摘要 :
Epithelial ion and fluid secretion determine the physiological functions of a broad range of organs, such as the lung, liver, or pancreas. The molecular mechanism of pancreatic ion secretion is challenging to investigate due to th...
展开
Epithelial ion and fluid secretion determine the physiological functions of a broad range of organs, such as the lung, liver, or pancreas. The molecular mechanism of pancreatic ion secretion is challenging to investigate due to the limited access to functional human ductal epithelia. Patient-derived organoids may overcome these limitations, however direct accessibility of the apical membrane is not solved. In addition, due to the vectorial transport of ions and fluid the intraluminal pressure in the organoids is elevated, which may hinder the study of physiological processes. To overcome these, we developed an advanced culturing method for human pancreatic organoids based on the removal of the extracellular matrix that induced an apical-to-basal polarity switch also leading to reversed localization of proteins with polarized expression. The cells in the apical-out organoids had a cuboidal shape, whereas their resting intracellular Ca2+ concentration was more consistent compared to the cells in the apical-in organoids. Using this advanced model, we demonstrated the expression and function of two novel ion channels, the Ca2+ activated Cl- channel Anoctamin 1 (ANO1) and the epithelial Na+ channel (ENaC), which were not considered in ductal cells yet. Finally, we showed that the available functional assays, such as forskolin-induced swelling, or intracellular Cl- measurement have improved dynamic range when performed with apical-out organoids. Taken together our data suggest that polarity-switched human pancreatic ductal organoids are suitable models to expand our toolset in basic and translational research.
收起
摘要 :
The kinetics of dissolution of kaolinite in industrial spent liquor followed by the precipitation of the desilication product was studied by using calcined and dimethyl sulfoxide intercalated Eckalite1 as starting material. These ...
展开
The kinetics of dissolution of kaolinite in industrial spent liquor followed by the precipitation of the desilication product was studied by using calcined and dimethyl sulfoxide intercalated Eckalite1 as starting material. These studies were aimed at understanding the influence of the combination of different pre-treatments on the vari-ations in the maximum silica concentrations and shift (or in some cases, the disappearance) of the trigger point in the Bayer desilication process. In addition to the quantitative characterization of the dissolution kinetics, a va-riety of physico-chemical parameters of the kaolinites, like the specific surface area, Lewis acidity, hydrodynamic diameter, zeta potential, optical band gap and thermogravimetric behaviour was also determined. From the experimental data, it can be concluded that the thermal/mechanochemical dehydroxylation and the formation of metakaolinite/mechanochemically amorphized kaolinite are responsible for the increase in the concentration of the dissolved silica in the supersaturated sodium aluminate solution. The variation in the position of the trigger point could be connected to the deformation, fragmentation/delamination, and amorphization of the kaolinite structure evolved during the mechanochemical pre-treatment. The joined application of pre-calcination and pre -milling verified the conclusions drawn. In addition, the combined treatment can be optimized to end up with a dissolution process that is carried out in a time and energy saving manner. The extent of the desilication products obtained at the end of the dissolution tests showed a considerable dependence on the applied pre-treatments: the formation of the metakaolinite phases was found to facilitate the evolution of the ball of yarn-type lepispherical structures with sizes ranging from 600 to 3000 nm.
收起
摘要 :
Certain members of the order Mucorales can cause a life-threatening, often-fatal systemic infection called mucormycosis. Mucormycosis has a high mortality rate, which can reach 96 to 100% depending on the underlying condition of t...
展开
Certain members of the order Mucorales can cause a life-threatening, often-fatal systemic infection called mucormycosis. Mucormycosis has a high mortality rate, which can reach 96 to 100% depending on the underlying condition of the patient. Mucorales species are intrinsically resistant to most antifungal agents, such as most of the azoles, which makes mucormycosis treatment challenging. The main target of azoles is the lanosterol 14a-demethylase (Erg11), which is responsible for an essential step in the biosynthesis of ergosterol, the main sterol component of the fungal membrane. Mutations in the erg11 gene can be associated with azole resistance; however, resistance can also be mediated by loss of function or mutation of other ergosterol biosynthetic enzymes, such as the sterol 24-C-methyltransferase (Erg6). The genome of Mucor lusitanicus encodes three putative erg6 genes (i.e., erg6a, erg6b, and erg6c). In this study, the role of erg6 genes in azole resistance of Mucor was analyzed by generating and analyzing knockout mutants constructed using the CRISPR-Cas9 technique. Susceptibility testing of the mutants suggested that one of the three genes, erg6b, plays a crucial role in the azole resistance of Mucor. The sterol composition of erg6b knockout mutants was significantly altered compared to that of the original strain, and it revealed the presence of at least four alternative sterol biosynthesis pathways leading to formation of ergosterol and other alternative, nontoxic sterol products. Dynamic operation of these pathways and the switching of biosynthesis from one to the other in response to azole treatment could significantly contribute to avoiding the effects of azoles by these fungi.IMPORTANCE The fungal membrane contains ergosterol instead of cholesterol, which offers a specific point of attack for the defense against pathogenic fungi. Indeed, most antifungal agents target ergosterol or its biosynthesis. Mucormycoses-causing fungi are resistant to most antifungal agents, including most of the azoles. For this reason, the drugs of choice to treat such infections are limited. The exploration of ergosterol biosynthesis is therefore of fundamental importance to understand the azole resistance of mucormycosis-causing fungi and to develop possible new control strategies. Characterization of sterol 24-C-methyltransferase demonstrated its role in the azole resistance and virulence of M. lusitanicus. Moreover, our experiments suggest that there are at least four alternative pathways for the biosynthesis of sterols in Mucor. Switching between pathways may contribute to the maintenance of azole resistance.
收起
摘要 :
The aim of the current prospective pilot study exclusively for deep-seated soft tissue sarcomas (STS) was to evaluate efficacy and safety of bleomycin-based ECT using VEG (variable electrode geometry) electrodes. During a 2-year p...
展开
The aim of the current prospective pilot study exclusively for deep-seated soft tissue sarcomas (STS) was to evaluate efficacy and safety of bleomycin-based ECT using VEG (variable electrode geometry) electrodes. During a 2-year period, seven surgically inoperable STSs were treated at the University of Szeged, Department of Surgery in Hungary. Electrode placement was determined by software planning using preoperative imaging (CT/MRI) and intraoperative ultrasound. Intravenous bleomycin (15.000 IU/m(2)) was administered 8 min before first pulse generation which lasted up to 40 min. Tumour response was evaluated through CT/MRI 2 months after treatment as per RECIST v.1.1. Five male-and 2 female patients were treated with fibromyxoid sarcoma (n = 2), epitheloid sarcoma (n = 3), liposarcoma (n = 1) and myofibroblastic sarcoma (n = 1) with median age of 54 years (49-88). Median tumour diameter, tumour volume and tumour depth was 5.9 cm (3.7-22.5), 131.13 cm(3) (35.6-2456.22) and 6.18 cm (3.74-18.18), respectively. Median operative time was 75 min (35-180), median hospital stay 2 days (2-20). Two month follow-up confirmed partial response in 5 patients, while stable disease in 1 patient, and progressive disease in 1 case as per RECIST v.1.1. Grade 2 ulceration was experienced in four cases, and a transient left musculus quadriceps femoris plegia occured in one patient. Local control of deep-seated STSs with BLM-based VEG ECT holds a promising perspective and our results may serve as a practical guide for further investigation and treatment planning.
收起
摘要 :
We investigated the application of pulsed laser ablation (PLA) for the production of magnetic nanoparticles (MNPs)/drug nanocomposites. Magnetic drug delivery vehicles can provide a multifunctional theranostic platform and allow f...
展开
We investigated the application of pulsed laser ablation (PLA) for the production of magnetic nanoparticles (MNPs)/drug nanocomposites. Magnetic drug delivery vehicles can provide a multifunctional theranostic platform and allow for a combination of diagnostics, monitoring and therapeutics. We applied nanosecond laser pulses at two different wavelengths (Nd:YAG laser, lambda (1) = 532 nm/lambda (2) = 1064 nm, FWHM = 6 ns) for the ablation of target tablets consisting of a mixture of ibuprofen (as a model drug) and magnetite NPs in various mass ratios. Fourier-transform infrared and Raman spectroscopy investigations of the ablated particles revealed that PLA induced no chemical changes in the pharmaceutical compound. The size distributions of the composite particles were established using a particle size analyzer (scanning mobility particle sizer), and 100-150 nm mean particle size values were obtained. SEM, energy dispersive x-ray spectroscopy and fast photography studies provided morphological and compositional information about the ablated particles. We demonstrated that PLA offers a simple and chemical free method for producing MNPs/drug nanocomposites, and it can be applied for the future development of new theranostic nanosystems.
收起
摘要 :
The aim of this study is to describe four new cases of trepanation from the Great Hungarian Plain and complement two other previously published cases with new results from the 9(th) to 16(th) c. CE. Sex determination and age-at-de...
展开
The aim of this study is to describe four new cases of trepanation from the Great Hungarian Plain and complement two other previously published cases with new results from the 9(th) to 16(th) c. CE. Sex determination and age-at-death estimation were performed using classical macromorphological methods. In certain cases, radiographic imaging, 3D scanning, and radiocarbon dating were also performed. Our cases fit the formerly established understanding of trepanations, with a male majority and signs of trauma as accompanying symptoms. The cause of intervention was mostly therapeutic, i.e., trauma, in most cases. In order to simplify the currently confusing nomenclature in trepanation categories (complete-incomplete vs. surgical-symbolic), we propose the use of "trepanation" exclusively to all forms of intentional, non-violent removals of all three layers of the cranial vault. On the other hand, the phenomena widely known in Eastern Europe as symbolic trepanations should be designated as "cranioglyphs," referring to all forms of superficial interventions administered to the cranial vault that do not penetrate all three layers of the bone. In case the data are insufficient to properly categorize the phenomenon at hand, one should refrain from it, and simply describe the lesion as intentional cranial intervention. In order to bring spotlight to the wide range of cranial interventions in the early medieval Carpathian Basin, our team is conducting several research projects, in order to contribute to a better understanding of these traditions in the future.
收起
摘要 :
In this paper, a rapid optical method for characterizing plasmonic (gold) nanoparticle (AuNP) adhesion is presented. Two different methods were used for AuNP preparation: the well-known Turkevich method resulted in particles with ...
展开
In this paper, a rapid optical method for characterizing plasmonic (gold) nanoparticle (AuNP) adhesion is presented. Two different methods were used for AuNP preparation: the well-known Turkevich method resulted in particles with negative surface charge; for preparing AuNPs with positive surface charge, stainless steel was used as reducing agent. The solid surface for adhesion was provided by a column packed with pristine or surface-modified glass beads. The size of the nanoparticles was studied by transmission electron microscopy (TEM) and small-angle X-ray scattering (SAXS); the surface charge of the components was determined by streaming potential measurements. The characterization of adhesion was performed in a flow system by UV-Vis spectroscopy. During the adhesion experiments, the role of the surface charge, the particle size, and the pH were studied, as well as the adhered amount of gold nanoparticles and the surface coverage values. The latter was estimated by theoretical calculations and defined by the quotient of the measured and the maximal adhered amount of nanoparticles, which could be determined by the cross-sectional area of the NPs and the specific surface area of the glass beads. The results are verified by the polarization reflectometric interference spectroscopy (PRIfS) method: silica nanoparticles with diameters of a few hundred (d~450) nanometers were immobilized on the surface of glass substrate by the Langmuir-Blodgett method, the surface was modified similar to the 3D (continuous flow packed column) system, and gold nanoparticles from different pH solutions were adhered during the measurements. These kinds of modified surfaces allow the investigation of biomolecule adsorption in the same reflectometric setup. Graphical abstract
收起
摘要 :
In this paper, the authors give a new insight to the indication and preparation of trepanations through the analysis of a newly discovered case of 10th-century-CE surgical trepanation found in the material of Sarretudvari-Poroshal...
展开
In this paper, the authors give a new insight to the indication and preparation of trepanations through the analysis of a newly discovered case of 10th-century-CE surgical trepanation found in the material of Sarretudvari-Poroshalom. We also intend to outline the implications of this particular case to the general methodology of trepanation research. We estimated basic anthropological data (sex and age-at-death) and performed analyses of paleopathological and activity-related lesions. Computed tomography, radiocarbon, and genetic analyses were also conduced. Beside other prior traumas, two codependent lesions were detected on the right parietal bone with no sign of healing. In this lesion complex, an original sharp force trauma was observable surrounded by two curved, intentionally created furrows, which can be interpreted as attempted surgical trepanation presumably performed with a U-shaped gouge. The results of the analysis of activity-related changes and archeological examination corroborate the assumption that the injuries described on the skull may have been, indeed, acquired during activities connected to military lifestyle, and the individual may have been a high-ranking military leader in his community. This unique case has paramount importance providing more detailed knowledge of past medical practices. The application of U-shaped gouge has not been formerly documented in the literature, which opens a new perspective both in the osteological investigation of these interventions and the archeological research concerning ancient medical technology. Our results may suggest a possible mode of tool use, and aid future reconstruction attempts concerning the hypothesized 10th-century-CE trepan from Tiszaeszlar-Bashalom.
收起
摘要 :
During wet granulation, the sample can be exposed to considerable mechanical effects, moisture content and elevated temperatures, and during high-shear granulation the impeller and chopper speeds can induce elevated temperatures a...
展开
During wet granulation, the sample can be exposed to considerable mechanical effects, moisture content and elevated temperatures, and during high-shear granulation the impeller and chopper speeds can induce elevated temperatures and influence the parameters of the products. In our work, we therefore aimed to investigate the effect of cooling and process parameters on product parameters by factorial design in accordance with QbD guidelines. Our other goal was to study the effect of the type of granulation, therefore two series were used to prepare granules in a high-shear granulator, with water and binder solution as granulating fluid, at different chopper and impeller speeds with application of factorial design. The particle size was higher when cooling in the case of granules prepared with binder solution. The pepsin solution had a good granulating effect, the granules displayed a larger particle size, a higher breaking hardness and a favourable deformation process. (c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).
收起
摘要 :
Tannic acid (TA) and glutathione (GSH) are important molecular antioxidants against reactive oxygen species. Their efficiency is limited by low solubility and high sensitivity, which may be solved by confinement in composite mater...
展开
Tannic acid (TA) and glutathione (GSH) are important molecular antioxidants against reactive oxygen species. Their efficiency is limited by low solubility and high sensitivity, which may be solved by confinement in composite materials. Here, effect of immobilization of these antioxidants on their radical scavenging activity was investigated using layered double hydroxide (LDH) nanoparticles as hosts. Different preparation methods were applied to build composite systems leading to variations in the molecular orientation of both TA and GSH on the surface or among the layers of LDHs. Systematic combination of spectroscopy (FT-IR, Raman, UV-VIS-NIR-DRS), diffraction (XRD) and microscopy (SEM) methods revealed perpendicular or parallel orientation of TA on the surface of LDH depending on the preparation approach applied. Immobilization of GSH protected the antioxidant molecules from degradation. Radical scavenging tests evidenced that the activity of the antioxidants strongly depends on the molecular orientation. The LDH supported GSH and TA proved as durable and reusable antioxidant agents to be applied as radical scavengers in medical therapies or in industrial processes. & COPY; 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).
收起
原文获取