Persistent use of nitrous oxide for anaesthesia in European hospitals despite its harmfulness to the climate - how emission taxation can achieve the coupling of cost-effectiveness and climate protection: observational study.

BACKGROUND: Health care has the intrinsic obligation to preserve health. This concept is also applicable to planetary health. Nitrous oxide (N2O) lacks clinical indications in modern anaesthesia, while it is a high-potential greenhouse gas. Its seemingly low cost contrasts with the consequential externalised socio-economic costs due to its contribution to the climate crisis, which is approximately €698 per emitted ton of CO2 equivalent. This difference can be internalised through emission taxation. In this study, we aim to evaluate how much N2O - total amount and converted to CO2 equivalent - is used at a German university hospital and compare this amount to that used at European hospitals. Furthermore, how the cost of N2O usage changes under different emission taxation scenarios is calculated. METHODS: This trial was a retrospective observational study at a German university hospital with approximately 1,250 beds between 2016 and 2020. Additionally, five European hospitals from the Health Care Without Harm Network were used for comparison from a European perspective. The main outcome parameters were the amount of N2O used, in total and converted to CO2 equivalent, and the total cost at emission taxation of €0, €25, €55 and €698 per ton CO2 equivalent. RESULTS: At the peak, 2,104 tCO2 equivalent in N2O was emitted in 2019. The actual cost was €14,040 in this year, while the corresponding socio-economic damage due to the climate crisis was almost €1.5 million. Other European hospitals showed comparable amounts of emissions. CONCLUSIONS: The annual peak amount of emitted N2O corresponded to the total annual greenhouse gas emission of 188 people in Germany. To achieve a drastic reduction in use, the abandonment of recommendations by anaesthesiologic societies appears necessary, in addition to an internalisation of future costs via emission taxation, which will cause inadequate cost for a medication without relevant benefit or indication. To that end, the inclusion of health sector emissions within national or international greenhouse gas taxation, for example, the European Union Emissions Trading System, appears necessary and expedient in view of the urgent need to address the ecological transformation. TRIAL REGISTRATION: The trial was registered with the German Clinical Trials Register, identifier DRKS00024973 on 12/04/2021.

Mitochondrial Impairment by MitoBloCK-6 Inhibits Liver Cancer Cell Proliferation.

Augmenter of liver regeneration (ALR) is a critical multi-isoform protein with its longer isoform, located in the mitochondrial intermembrane space, being part of the mitochondrial disulfide relay system (DRS). Upregulation of ALR was observed in multiple forms of cancer, among them hepatocellular carcinoma (HCC). To shed light into ALR function in HCC, we used MitoBloCK-6 to pharmacologically inhibit ALR, resulting in profound mitochondrial impairment and cancer cell proliferation deficits. These effects were mostly reversed by supplementation with bioavailable hemin b, linking ALR function to mitochondrial iron homeostasis. Since many tumor cells are known for their increased iron demand and since increased iron levels in cancer are associated with poor clinical outcome, these results help to further advance the intricate relation between iron and mitochondrial homeostasis in liver cancer.

Further engineering of R. toruloides for the production of terpenes from lignocellulosic biomass.

BACKGROUND: Mitigation of climate change requires that new routes for the production of fuels and chemicals be as oil-independent as possible. The microbial conversion of lignocellulosic feedstocks into terpene-based biofuels and bioproducts represents one such route. This work builds upon previous demonstrations that the single-celled carotenogenic basidiomycete, Rhodosporidium toruloides, is a promising host for the production of terpenes from lignocellulosic hydrolysates. RESULTS: This study focuses on the optimization of production of the monoterpene 1,8-cineole and the sesquiterpene α-bisabolene in R. toruloides. The α-bisabolene titer attained in R. toruloides was found to be proportional to the copy number of the bisabolene synthase (BIS) expression cassette, which in turn influenced the expression level of several native mevalonate pathway genes. The addition of more copies of BIS under a stronger promoter resulted in production of α-bisabolene at 2.2 g/L from lignocellulosic hydrolysate in a 2-L fermenter. Production of 1,8-cineole was found to be limited by availability of the precursor geranylgeranyl pyrophosphate (GPP) and expression of an appropriate GPP synthase increased the monoterpene titer fourfold to 143 mg/L at bench scale. Targeted mevalonate pathway metabolite analysis suggested that 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGR), mevalonate kinase (MK) and phosphomevalonate kinase (PMK) may be pathway bottlenecks are were therefore selected as targets for overexpression. Expression of HMGR, MK, and PMK orthologs and growth in an optimized lignocellulosic hydrolysate medium increased the 1,8-cineole titer an additional tenfold to 1.4 g/L. Expression of the same mevalonate pathway genes did not have as large an impact on α-bisabolene production, although the final titer was higher at 2.6 g/L. Furthermore, mevalonate pathway intermediates accumulated in the mevalonate-engineered strains, suggesting room for further improvement. CONCLUSIONS: This work brings R. toruloides closer to being able to make industrially relevant quantities of terpene from lignocellulosic biomass.