Particle swarm optimization for a hybrid freight train powered by hydrogen or ammonia solid oxide fuel cells

All diesel-only trains in the UK will be phased out by 2040. Hydrogen and ammonia emerge as alternative zero-carbon fuel for greener railway. Solid Oxide Fuel Cells (SOFCs) provide an alternative prime mover option, which efficiently convert zero-carbon fuels into electricity without emitting nitrogen oxides (NOx), unlike traditional engines. Superior to Proton Exchange Membrane Fuel Cells (PEMFCs) in efficiency, SOFCs fulfil MW-scale power needs and can use ammonia directly. This study investigates innovative strategies for integrating SOFCs into hybrid rail powertrains using hydrogen or ammonia. Utilizing an optimization framework incorporating Particle Swarm Optimization (PSO), the study aims to minimize operational costs while considering capital and replacement expenditures, powertrain performance, and component sizing. The findings suggest that hybrid powertrains based on ammonia-fueled SOFCs may potentially reduce costs by 30% compared to their hydrogen counterparts, albeit requiring additional space for engine compartments. Ammonia-fueled SOFCs trains also exhibit a 5% higher efficiency at End-of-Life (EoL), showing less performance degradation than those powered by hydrogen. The State of Charge (SoC) of the batteries in range of 30–70% for both cases is identified as most cost-effective

Hydrogen supply chain for future hydrogen-fuelled railway in the UK:Transport sector focused

Though being attractive on railway decarbonisation for regional lines, excessive cost caused by immature hydrogen supply chain is one of the significant hurdles for promoting hydrogen traction to rolling stocks. Therefore, we conduct bespoke research on the UK's hydrogen supply chain for railway, concentrating on hydrogen transportation. Firstly, a map for the planned hydrogen production plants and potential hydrogen lines is developed with the location, capacity, and usage. A spatially explicit model for the hydrogen supply chain is then introduced, which optimises the existing grid-based methodology on accuracy and applicability. Compressed hydrogen at three pressures, and liquid hydrogen are considered as the mediums, incorporating by road and rail transport. Furthermore, three scenarios for hydrogen rail penetration are simulated respectively to discuss the levelised cost and the most suitable national transport network. The results show that the developed model with mix-integer linear programming (MILP) can well design the UK's hydrogen distribution for railway traction. Moreover, the hydrogen transport medium and vehicle should adjust to suit for different era where the penetration of hydrogen traction varies. The levelised cost of hydrogen (LCOH) decreases from 6.13 £/kg to 5.13 £/kg on average from the conservative scenario to the radical scenario. Applying different transport combinations according to the specific situation can satisfy the demand while reducing cost for multi-supplier and multi-targeting hydrogen transport.<br/

Heat shock transcription factor 1 preserves cardiac angiogenesis and adaptation during pressure overload

To examine how heat shock transcription factor 1 (HSF1) protects against maladaptive hypertrophy during pressure overload, we subjected HSF1 transgenic (TG), knockout (KO) and wild type (WT) mice to a constriction of transverse aorta (TAC), and found that cardiac hypertrophy, functions and angiogenesis were well preserved in TG mice but were decreased in KO mice compared to WT ones at 4 weeks, which was related to HIF-1 and p53 expression. Inhibition of angiogenesis suppressed cardiac adaptation in TG mice while overexpression of angiogenesis factors improved maladaptive hypertrophy in KO mice. In vitro formation of vasculatures by microvascular endothelial cells was higher in TG mice but lower in KO mice than in WT ones. A siRNA of p53 but not a HIF-1 gene significantly reversed maladaptive hypertrophy in KO mice whereas a siRNA of HIF-1 but not a p53 gene induced maladaptive hypertrophy in TG mice. Heart microRNA analysis showed that miR-378 and miR-379 were differently changed among the three mice after TAC, and miR-378 or siRNA of miR-379 could maintain cardiac adaptation in WT mice. These results indicate that HSF1 preserves cardiac adaptation during pressure overload through p53-HIF-1-associated angiogenesis, which is controlled by miR-378 and miR-379

VS-4718 Antagonizes Multidrug Resistance in ABCB1- and ABCG2-Overexpressing Cancer Cells by Inhibiting the Efflux Function of ABC Transporters

Overexpression of ATP-binding cassette (ABC) transporters is one of the most important mechanisms responsible for multi-drug resistance (MDR). VS-4718, a tyrosine kinase inhibitor targeting focal adhesion kinase (FAK) with a potential anticancer effect, is currently evaluated in clinical trials. In this study, we investigated whether VS-4718 could reverse MDR mediated by ABC transporters, including ABCB1, ABCG2, and ABCC1. The results showed that VS-4718 significantly reversed ABCB1- and ABCG2-mediated MDR, but not MDR mediated by ABCC1. Treatment of VS-4718 did not alter the protein level and subcellular localization of ABCB1 or ABCG2. Mechanism studies indicated that the reversal effects of VS-4718 were related to attenuation of the efflux activity of ABCB1 and ABCG2 transporters. ATPase analysis indicated that VS-4718 stimulated the ATPase activity of ABCB1 and ABCG2. Docking study showed that VS-4718 interacted with the substrate-binding sites of both ABCB1 and ABCG2, suggesting that VS-4718 may affect the activity of ABCB1 and ABCG2 competitively. This study provided a novel insight for MDR cancer treatment. It indicated that combination of VS-4718 with antineoplastic drugs could attenuate MDR mediated by ABCB1 or ABCG2 in ABCB1- or ABCG2-overexpressing cancer cells

Impact of stress hyperglycemia ratio on mortality in patients with critical acute myocardial infarction: insight from American MIMIC-IV and the Chinese CIN-II study

Background: Among patients with acute coronary syndrome and percutaneous coronary intervention, stress hyperglycemia ratio (SHR) is primarily associated with short-term unfavorable outcomes. However, the relationship between SHR and long-term worsen prognosis in acute myocardial infarction (AMI) patients admitted in intensive care unit (ICU) are not fully investigated, especially in those with different ethnicity. This study aimed to clarify the association of SHR with all-cause mortality in critical AMI patients from American and Chinese cohorts. Methods: Overall 4,337 AMI patients with their first ICU admission from the American Medical Information Mart for Intensive Care (MIMIC)-IV database (n = 2,166) and Chinese multicenter registry cohort Cardiorenal ImprovemeNt II (CIN-II, n = 2,171) were included in this study. The patients were divided into 4 groups based on quantiles of SHR in both two cohorts. Results: The total mortality was 23.8% (maximum follow-up time: 12.1 years) in American MIMIC-IV and 29.1% (maximum follow-up time: 14.1 years) in Chinese CIN-II. In MIMIC-IV cohort, patients with SHR of quartile 4 had higher risk of 1-year (adjusted hazard radio [aHR] = 1.87; 95% CI: 1.40–2.50) and long-term (aHR = 1.63; 95% CI: 1.27–2.09) all-cause mortality than quartile 2 (as reference). Similar results were observed in CIN-II cohort (1-year mortality: aHR = 1.44; 95%CI: 1.03–2.02; long-term mortality: aHR = 1.32; 95%CI: 1.05–1.66). In both two group, restricted cubic splines indicated a J-shaped correlation between SHR and all-cause mortality. In subgroup analysis, SHR was significantly associated with higher 1-year and long-term all-cause mortality among patients without diabetes in both MIMIC-IV and CIN-II cohort. Conclusion: Among critical AMI patients, elevated SHR is significantly associated with and 1-year and long-term all-cause mortality, especially in those without diabetes, and the results are consistently in both American and Chinese cohorts

Glesatinib, a c-MET/SMO Dual Inhibitor, Antagonizes P-glycoprotein Mediated Multidrug Resistance in Cancer Cells

Multidrug resistance (MDR) is one of the leading causes of treatment failure in cancer chemotherapy. One major mechanism of MDR is the overexpressing of ABC transporters, whose inhibitors hold promising potential in antagonizing MDR. Glesatinib is a dual inhibitor of c-Met and SMO that is under phase II clinical trial for non-small cell lung cancer. In this work, we report the reversal effects of glesatinib to P-glycoprotein (P-gp) mediated MDR. Glesatinib can sensitize paclitaxel, doxorubicin, colchicine resistance to P-gp overexpressing KB-C2, SW620/Ad300, and P-gp transfected Hek293/ABCB1 cells, while has no effect to their corresponding parental cells and negative control drug cisplatin. Glesatinib suppressed the efflux function of P-gp to [3H]-paclitaxel and it didn't impact both the expression and cellular localization of P-gp based on Western blot and immunofluorescent analysis. Furthermore, glesatinib can stimulate ATPase in a dose-dependent manner. The docking study indicated that glesatinib interacted with human P-gp through several hydrogen bonds. Taken together, c-Met/SMO inhibitor glesatinib can antagonize P-gp mediated MDR by inhibiting its cell membrane transporting functions, suggesting new application in clinical trials