The Fight against Cancer by Microgravity: The Multicellular Spheroid as a Metastasis Model

Cancer is a disease exhibiting uncontrollable cell growth and spreading to other parts of the organism. It is a heavy, worldwide burden for mankind with high morbidity and mortality. Therefore, groundbreaking research and innovations are necessary. Research in space under microgravity (µg) conditions is a novel approach with the potential to fight cancer and develop future cancer therapies. Space travel is accompanied by adverse effects on our health, and there is a need to counteract these health problems. On the cellular level, studies have shown that real (r-) and simulated (s-) µg impact survival, apoptosis, proliferation, migration, and adhesion as well as the cytoskeleton, the extracellular matrix, focal adhesion, and growth factors in cancer cells. Moreover, the µg-environment induces in vitro 3D tumor models (multicellular spheroids and organoids) with a high potential for preclinical drug targeting, cancer drug development, and studying the processes of cancer progression and metastasis on a molecular level. This review focuses on the effects of r- and s-µg on different types of cells deriving from thyroid, breast, lung, skin, and prostate cancer, as well as tumors of the gastrointestinal tract. In addition, we summarize the current knowledge of the impact of µg on cancerous stem cells. The information demonstrates that µg has become an important new technology for increasing current knowledge of cancer biology.     

Reaktionen des 2,6-Di-tert.-butyl-4-(N-tert.-butylnitrono)-phenoxyradikals

Reactions of the 2,6-Di-tert.-butyl-4-(N-tert.-butylnitrono)-phenoxyl Radical The title compound, a phenoxyl radical containing a nitrono group, reacts with alcohols and tert.-butylhydroperoxide yielding phenol and products of secondary radical solvent reactions. The reactions with lead tetraacetate, tert.-butoxy and 2-cyanoisopropyl radicals give high yields of cyclohexadienone adducts ( 6, 7 and 10 ) containing unchanged nitrono function. The reaction with dibenzoylperoxide, however, leads to the modification of the nitrono group yielding the N-benzoyloxycarboxamide ( 8 ). In the acidic decomposition of the tert.-butoxy radical adduct we suggest a nitrenium ion ( 16 ) as an intermediate.     

Impacts of CO2 emission constraints on technology selection and energy resources for power generation in Bangladesh

This paper examines the impacts of CO₂ emission reduction target and carbon tax on future technologies selection and energy use in Bangladesh power sector during 2005–2035. The analyses are based on a long-term energy system model of Bangladesh using the MARKAL framework. The analysis shows that Bangladesh will not be able to meet the future energy demand without importing energy. However, alternative policies on CO₂ emission constraints reduce the burden of imported fuel, improve energy security and reduce environmental impacts. The results show that the introduction of the CO₂ emission reduction targets and carbon taxes directly affect the shift of technologies from high carbon content fossil-based to low carbon content fossil-based and clean renewable energy-based technologies compared to the base scenario. With the cumulative CO₂ emission reduction target of 10–20% and carbon tax of 2500 Taka/ton, the cumulative net energy imports during 2005–2035 would be reduced in the range of 39–65% and 37%, respectively, compared to the base scenario emission level. The total primary energy requirement would be reduced in the range of 4.5–22.3% in the CO₂ emission reduction targets and carbon tax 2500 Taka/ton scenarios and the primary energy supply system would be diversified compared to the base scenario.     

Nitroreductase-Mediated Release of Inhibitors of Lysine-Specific Demethylase 1 (LSD1) from Prodrugs in Transfected Acute Myeloid Leukaemia Cells

Lysine-specific demethylase 1 (LSD1) has evolved as a promising therapeutic target for cancer treatment, especially in acute myeloid leukaemia (AML). To approach the challenge of site-specific LSD1 inhibition, we developed an enzyme-prodrug system with the bacterial nitroreductase NfsB (NTR) that was expressed in the virally transfected AML cell line THP1-NTR⁺. The cellular activity of the NTR was proven with a new luminescent NTR probe. We synthesised a diverse set of nitroaromatic prodrugs that by design do not affect LSD1 and are reduced by the NTR to release an active LSD1 inhibitor. The emerging side products were differentially analysed using negative controls, thereby revealing cytotoxic effects. The 2-nitroimidazolyl prodrug of a potent LSD1 inhibitor emerged as one of the best prodrug candidates with a pronounced selectivity window between wild-type and transfected THP1 cells. Our prodrugs are selectively activated and release the LSD1 inhibitor locally, proving their suitability for future targeting approaches.     

Environmental Control of Triplet Emission in Donor–Bridge–Acceptor Organometallics

Carbene‐metal‐amides (CMAs) are a promising family of donor–bridge–acceptor molecular charge‐transfer (CT) emitters for organic light‐emitting diodes. A universal approach is demonstrated to tune the energy of their CT emission. A blueshift of up to 210 meV is achievable in solid state via dilution in a polar host matrix. The origin of this shift has two components: constraint of thermally‐activated triplet diffusion, and electrostatic interactions between guest and polar host. This allows the emission of mid‐green CMA archetypes to be tuned to sky blue without chemical modifications. Monte‐Carlo simulations based on a Marcus‐type transfer integral successfully reproduce the concentration‐ and temperature‐dependent triplet diffusion process, revealing a substantial shift in the ensemble density of states in polar hosts. In gold‐bridged CMAs, this shift does not lead to a significant change in luminescence lifetime, thermal activation energy, reorganization energy, or intersystem crossing rate. These discoveries offer new insight into coupling between the singlet and triplet manifolds in CMA materials, revealing a dominant interaction between states of CT character. The same approach is employed using materials which have been chemically modified to alter the energy of their CT state directly, shifting the emission of sky‐blue chromophores into the practical blue range.     

Optimizing 100%‐renewable grids through shifting residential water‐heater load

A low‐carbon electricity supply for Australia was simulated, and the installed capacity of the electrical grid was optimized by shifting the electricity demand of residential electric water heaters (EWHs). The load‐shifting potential of Australia was estimated for each hour of the simulation period using a nationwide aggregate EWH load model on a 90 × 110 raster grid. The electricity demand of water heaters was shifted from periods of low renewable resource and high demand to periods of high renewable resource and low demand, enabling us to effectively reduce the installed capacity requirements of a 100%‐renewable electricity grid. It was found that by shifting the EWH load by just 1 hour, the electricity demand of Australia could be met using purely renewable electricity at an installed capacity of 145 GW with a capacity factor of 30%, an electricity spillage of 20%, and a generation cost of 15.2 ¢/kWh. A breakdown of the primary energy sources used in our scenario is as follows: 43% wind, 29% concentrated solar thermal power, and 20% utility photovoltaic. Sensitivity analysis suggested that further reduction in installed capacity is possible by increasing the load‐shifting duration as well as the volume and insulation level of the EWH tank.