Cytotoxicity of aporphines in human colon cancer cell lines HCT-116 and Caco-2: An SAR study

A series of synthetic aporphine derivatives structurally related to domesticine and nantenine (ring A, N6 and ring C truncated analogs), was evaluated in MTS cytotoxicity assays against the human colon cancer cell lines, HCT-116 and Caco-2. In general, the C1 position of ring A is tolerant of alkoxy substituents as well as a benzoyl ester functionality. Other modifications evaluated resulted in a decrease in cytotoxic activity. The most potent compounds identified had IC50 values in the range 23–38 μM, comparable to the known cytotoxic agent, etoposide

Simplified model of battery energy-stored quasi-Z-source inverter-based photovoltaic power plant with Twofold energy management system

The use of a battery energy-stored quasi-Z-source inverter (BES-qZSI) for large-scale PV power plants exhibits promising features due to the combination of qZSI and battery as energy storage system, such as single-stage power conversion (without additional DC/DC boost converter), improvements in the output waveform quality (due to the elimination of switching dead time), and continuous and smooth delivery of energy to the grid (through the battery energy storage system). This paper presents a new simplified model of a BES-qZSI to represent the converter dynamics with sufficient accuracy while using a less complex model than the detailed model (including the modelling of all switches and switching pulses). It is based on averaged values of the variables, voltage/current sources, and the same control circuit than the detailed model, except for the switching pulses generation. The simplified model enables faster time-domain simulation and is useful for control design and dynamic analysis purposes. Additionally, an energy management system has been developed to govern the power supply to grid under two possible scenarios: 1) System operator command following; or 2) economic dispatch of the stored energy. The results obtained from simulations and experimental hardware-in-the-loop (HIL) setup for different operating conditions of the grid-connected large-scale PV power plant with battery energy storage under study demonstrate the validity of the proposed simplified model to represent the dynamics of the converter and PV power plant for steady-state stability studies, long-term simulations, or large electric power systems. © 2021 The AuthorsThis work was partially supported by the Spain's Ministerio de Ciencia, Innovaci?n y Universidades (MCIU), Agencia Estatal de Investigaci?n (AEI), and Fondo Europeo de Desarrollo Regional (FEDER) Uni?n Europea (UE) (grant number RTI2018-095720-B-C32), by the Federal Center for Technological Education of Minas Gerais, Brazil (process number 23062?010087/2017-51) and by the National Council of Technological and Scientific Development (CNPq-Brazil

Model Predictive Control-Based Optimized Operation of a Hybrid Charging Station for Electric Vehicles

This paper presents an energy management system (EMS) based on a novel approach using model predictive control (MPC) for the optimized operation of power sources in a hybrid charging station for electric vehicles (EVs). The hybrid charging station is composed of a photovoltaic (PV) system, a battery, a complete hydrogen system based on a fuel cell (FC), electrolyzer (EZ), and tank as an energy storage system (ESS), grid connection, and six fast charging units, all of which are connected to a common MVDC bus through Z-source converters (ZSC). The MPC-based EMS is designed to control the power flow among the energy sources of the hybrid charging station and reduce the utilization costs of the ESS and the dependency on the grid. The viability of the EMS was proved under a long-term simulation of 25 years in Simulink, using real data for the sun irradiance and a European load profile for EVs. Furthermore, this EMS is compared with a simpler alternative that is used as a benchmark, which pursues the same objectives, although using a states-based strategy. The results prove the suitability of the EMS, achieving a lower utilization cost (-25.3%), a notable reduction in grid use (-60% approximately) and an improvement in efficiency

Understanding the neurological implications of acute and long COVID using brain organoids

As early as in the acute phase of the coronavirus disease 2019 about the long-term implications of infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), like many other viruses, can trigger chronic disorders that last months or even years. Long COVID, the chronic and persistent disorder lasting more than 12 weeks after the primary infection with SARS-CoV-2, involves a variable number of neurological manifestations, ranging from mild to severe and even fatal. In vitro and in vivo modeling suggest that SARS-CoV-2 infection drives changes within neurons, glia and the brain vasculature. In this Review, we summarize the current understanding of the neuropathology of acute and long COVID, with particular emphasis on the knowledge derived from brain organoid models. We highlight the advantages and main limitations of brain organoids, leveraging their humanoerived origin, their similarity in cellular and tissue architecture to human tissues, and their potential to decipher the pathophysiology of long COVID

Transformer‐Based Z‐Source Inverter with MVDC Link

Z‐source inverters have attracted considerable attention in renewable energy systems like photovoltaic (PV) systems due to advantages such as buck–boost power conversion in single stage, shoot-through capability, and wide range of input voltage regulation. Transformer-Based Z-source inverters (TransZSI) based on magnetically coupled inductors and reduced number of passive components can be used to improve the boost capacity of these inverters, and to increase the voltage levels. Medium voltage DC (MVDC) is being used more and more in distribution grids and renewable energy systems. This paper presents a transZ-source inverter with MVDC link where renewable energy systems and energy storage systems can be integrated. The active and reactive powers and DC voltage are controlled by acting on the modulation index and shoot-through duty cycle of the converter. The trans-Z-source inverter is evaluated under different operating conditions to illustrate its suitable operation. © 2022, European Association for the Development of Renewable Energy, Environment and Power Quality (EA4EPQ). All rights reserved

Persistence of anticancer activity in berry extracts after simulated gastrointestinal digestion and colonic fermentation

Fruit and vegetable consumption is associated at the population level with a protective effect against colorectal cancer. Phenolic compounds, especially abundant in berries, are of interest due to their putative anticancer activity. After consumption, however, phenolic compounds are subject to digestive conditions within the gastrointestinal tract that alter their structures and potentially their function. However, the majority of phenolic compounds are not efficiently absorbed in the small intestine and a substantial portion pass into the colon. We characterized berry extracts (raspberries, strawberries, blackcurrants) produced by in vitro-simulated upper intestinal tract digestion and subsequent fecal fermentation. These extracts and selected individual colonic metabolites were then evaluated for their putative anticancer activities using in vitro models of colorectal cancer, representing the key stages of initiation, promotion and invasion. Over a physiologically-relevant dose range (0–50 µg/ml gallic acid equivalents), the digested and fermented extracts demonstrated significant anti-genotoxic, anti-mutagenic and anti-invasive activity on colonocytes. This work indicates that phenolic compounds from berries undergo considerable structural modifications during their passage through the gastrointestinal tract but their breakdown products and metabolites retain biological activity and can modulate cellular processes associated with colon cancer

Neuroprotective effects of selected microbial-derived phenolic metabolites and aroma compounds from wine in human SH-SY5Y neuroblastoma cells and their putative mechanisms of action

Moderate wine consumption has shown the potential to delay the onset of neurodegenerative diseases. This study investigates the molecular mechanisms underlying the protective effects of wine-derived phenolic and aroma compounds in a neuroinflammation model based on SIN-1 stress-induced injury in SH-SY5Y neuroblastoma cells. Cell pretreatment with microbial metabolites found in blood after wine consumption, 3,4-dihydroxyphenylacetic (3,4-DHPA), 3-hydroxyphenylacetic acids and salicylic β-d-O-glucuronide, at physiologically concentrations (0.1-10 μM) resulted in increased cell viability versus SIN-1 control group (p < 0.05). Results also showed significant decreases in mitogen-activated protein kinase (MAPK) p38 and ERK1/2 activation as well as in downstream pro-apoptotic caspase-3 activity by some of the studied compounds. Moreover, pretreatment with p38, MEK, and ERK1/2-specific inhibitors, which have a phenolic-like structure, also resulted in an increase on cell survival and a reduction on caspase-3 activity levels. Overall, these results contribute with new evidences related to the neuroprotective actions of wine, pointing out that wine-derived human metabolites and aroma compounds may be effective at protecting neuroblastoma cells from nitrosative stress injury by inhibiting neuronal MAPK p38 and ERK1/2, as well as downstream caspase 3 activity

Personalized assessment of the cumulative complication risk of the atrial fibrillation ablation track: The AF-TRACK calculator

Atrial fibrillation (AF) ablation strategy is associated with a non-negligible risk of complications and often requires repeat procedures (AF ablation track), implying repetitive exposure to procedural risk.The purpose of this study was to develop and validate a model to estimate individualized cumulative risk of complications in patients undergoing the AF ablation track (Atrial Fibrillation TRAck Complication risK [AF-TRACK] calculator).The model was derived from a multicenter cohort including 3762 AF ablation procedures in 2943 patients. A first regression model was fitted to predict the propensity for repeat ablation. The AF-TRACK calculator computed the risk of AF ablation track complications, considering the propensity for repeat ablation. Internal (cross-validation) and external (independent cohort) validation were assessed for discrimination capacity (area under the curve [AUC]) and goodness of fit (Hosmer-Lemeshow [HL] test).Complications (N = 111) occurred in 3.7% of patients (2.9% of procedures). Predictors included female sex, heart failure, sleep apnea syndrome, and repeat procedures. The model showed fair discrimination capacity to predict complications (AUC 0.61 [0.55-0.67]) and likelihood of repeat procedure (AUC 0.62 [0.60-0.64]), with good calibration (HL χ2 12.5; P = .13). The model maintained adequate discrimination capacity (AUC 0.67 [0.57-0.77]) and calibration (HL χ2 5.6; P = .23) in the external validation cohort. The validated model was used to create the Web-based AF-TRACK calculator.The proposed risk model provides individualized estimates of the cumulative risk of complications of undergoing the AF ablation track. The AF-TRACK calculator is a validated, easy-to-use, Web-based clinical tool to calibrate the risk-to-benefit ratio of this treatment strategy.© 2022 Heart Rhythm Society. Published by Elsevier Inc

Regulation of cell death receptor S-nitrosylation and apoptotic signaling by Sorafenib in hepatoblastoma cells

Nitric oxide (NO) plays a relevant role during cell death regulation in tumor cells. The overexpression of nitric oxide synthase type III (NOS-3) induces oxidative and nitrosative stress, p53 and cell death receptor expression and apoptosis in hepatoblastoma cells. S-nitrosylation of cell death receptor modulates apoptosis. Sorafenib is the unique recommended molecular-targeted drug for the treatment of patients with advanced hepatocellular carcinoma. The present study was addressed to elucidate the potential role of NO during Sorafenib-induced cell death in HepG2 cells. We determined the intra- and extracellular NO concentration, cell death receptor expression and their S-nitrosylation modifications, and apoptotic signaling in Sorafenib-treated HepG2 cells. The effect of NO donors on above parameters has also been determined. Sorafenib induced apoptosis in HepG2 cells. However, low concentration of the drug (10nM) increased cell death receptor expression, as well as caspase-8 and -9 activation, but without activation of downstream apoptotic markers. In contrast, Sorafenib (10 µM) reduced upstream apoptotic parameters but increased caspase-3 activation and DNA fragmentation in HepG2 cells. The shift of cell death signaling pathway was associated with a reduction of S-nitrosylation of cell death receptors in Sorafenib-treated cells. The administration of NO donors increased S-nitrosylation of cell death receptors and overall induction of cell death markers in control and Sorafenib-treated cells. In conclusion, Sorafenib induced alteration of cell death receptor S-nitrosylation status which may have a relevant repercussion on cell death signaling in hepatoblastoma cells.Instituto de Salud Carlos III PI13/00021Ministerio de Economía y Competitividad BFU2012-32056Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía BIO-0216Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía CTS-6264Consejería de Salud, Junta de Andalucía PI13/ 0002