Active Transport of Hepatotoxic Pyrrolizidine Alkaloids in HepaRG Cells

1,2-unsaturated pyrrolizidine alkaloids (PAs) are secondary plant metabolites occurring as food contaminants that can cause severe liver damage upon metabolic activation in hepatocytes. However, it is yet unknown how these contaminants enter the cells. The role of hepatic transporters is only at the beginning of being recognized as a key determinant of PA toxicity. Therefore, this study concentrated on assessing the general mode of action of PA transport in the human hepatoma cell line HepaRG using seven structurally different PAs. Furthermore, several hepatic uptake and efflux transporters were targeted with pharmacological inhibitors to identify their role in the uptake of the PAs retrorsine and senecionine and in the disposition of their N-oxides (PANO). For this purpose, PA and PANO content was measured in the supernatant using LC-MS/MS. Also, PA-mediated cytotoxicity was analyzed after transport inhibition. It was found that PAs are taken up into HepaRG cells in a predominantly active and structure-dependent manner. This pattern correlates with other experimental endpoints such as cytotoxicity. Pharmacological inhibition of the influx transporters Na⁺/taurocholate co-transporting polypeptide (SLC10A1) and organic cation transporter 1 (SLC22A1) led to a reduced uptake of retrorsine and senecionine into HepaRG cells, emphasizing the relevance of these transporters for PA toxicokinetics.     

Sintering behaviour of fluorapatite–silicate composites produced from natural fluorapatite and quartz

In this work, the sintering behaviour of fluorapatite (FAp)–silicate composites prepared by mixing variable amounts of natural quartz (2.5 wt% to 20 wt%) and FAp was studied. The composites were pressureless sintered in air at temperatures from 1000 °C to 1350 °C. The effects of temperatures on the densification, phase formation, chemical bonding and Vickers hardness of the composites were evaluated. All the samples exhibited mixed phase, comprising FAp and francolite as the major constituents along with some minor phases of cristobalite, wollastonite, dicalcium silicate and/or whitlockite dependent on the quartz content and sintering temperature. The composite containing 2.5 wt% quartz exhibited the best sintering properties. The highest bulk density of 3 g/cm³ and a Vickers hardness of >4.2 GPa were obtained for the 2.5 wt% quartz–FAp composite when sintered at 1100 °C. The addition of quartz was found to alter the microstructure of the composites, where it exhibited a rod-like morphology when sintered at 1000 °C and a regular rounded grain structure when sintered at 1350 °C. A wetted grain surface was observed for composites containing high quartz content and was believed to be associated with a transient liquid phase sintering.     

Mixed-Metal MOF-74 Templated Catalysts for Efficient Carbon Dioxide Capture and Methanation

The vast chemical and structural tunability of metal–organic frameworks (MOFs) are beginning to be harnessed as functional supports for catalytic nanoparticles spanning a range of applications. However, a lack of straightforward methods for producing nanoparticle-encapsulated MOFs as efficient heterogeneous catalysts limits their usage. Herein, a mixed-metal MOF, NiMg-MOF-74, is utilized as a template to disperse small Ni nanoclusters throughout the parent MOF. By exploiting the difference in Ni O and Mg O coordination bond strength, Ni²⁺ is selectively reduced to form highly dispersed Ni nanoclusters constrained by the parent MOF pore diameter, while Mg²⁺ remains coordinated in the framework. By varying the ratio of Ni to Mg in the parent MOF, accessible surface area and crystallinity can be tuned upon thermal treatment, influencing CO₂ adsorption capacity and hydrogenation selectivity. The resulting Ni nanoclusters prove to be an active catalyst for CO₂ methanation and are examined using extended X-ray absorption fine structure and X-ray photoelectron spectroscopy. By preserving a segment of the Mg²⁺-containing MOF framework, the composite system retains a portion of its CO₂ adsorption capacity while continuing to deliver catalytic activity. The approach is thus critical for designing materials that can bridge the gap between carbon capture and CO₂ utilization.     

Control of reactive distillation production of high-purity isopropanol

The process characteristics and control strategy of a high-purity IPA reactive distillation column were investigated. A robust nominal operation was found by maintaining an excess of propylene feed to the column and recycling the unreacted propylene to the feed instead of the top stage. Stage temperature and propylene composition with one-to-one relationship with reboiler duty and propylene feed are selected as controlled variables for maintaining bottom purity and feed ratio in the presence of possible measurement bias respectively. High nonlinearity between selected input–output pair was reduced by using variable transformation. Dynamic simulations demonstrated that such a control scheme with nonlinear transformed variable was capable of providing much superior control performance than the one using natural variable.     

The method of double averaging: an approach for modeling power-factor-correction switching converters

This paper describes the modeling of power-factor-correction converters under average-current-mode control, which are widely used in switch-mode power supply applications. The objective is to identify stability boundaries in terms of major circuit parameters for facilitating design of such converters. The approach employs a double averaging procedure, which first applies the usual averaging over the switching period and subsequently applies generalized averaging over the mains period. The resulting model, after two averaging steps and application of a harmonic balance procedure, is nonlinear and capable of describing the low-frequency nonlinear dynamics of the system. The parameter ranges within which stable operation is guaranteed can be accurately and easily found using this model. Experimental measurements are provided for verification of the analytical results.