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In the era of precision cosmology, it is essential to determine the Hubble constant empirically with an accuracy of one per cent or better 1 . At present, the uncertainty on this constant is dominated by the uncertainty in the calibration of the Cepheid period–luminosity relationship 2 , 3 (also known as the Leavitt law). The Large Magellanic Cloud has traditionally served as the best galaxy with which to calibrate Cepheid period–luminosity relations, and as a result has become the best anchor point for the cosmic distance scale 4 , 5 . Eclipsing binary systems composed of late-type stars offer the most precise and accurate way to measure the distance to the Large Magellanic Cloud. Currently the limit of the precision attainable with this technique is about two per cent, and is set by the precision of the existing calibrations of the surface brightness–colour relation 5 , 6 . Here we report a calibration of the surface brightness–colour relation with a precision of 0.8 per cent. We use this calibration to determine a geometrical distance to the Large Magellanic Cloud that is precise to 1 per cent based on 20 eclipsing binary systems. The final distance is 49.59 ± 0.09 (statistical) ± 0.54 (systematic) kiloparsecs. A new calibration of the surface brightness–colour relation of eclipsing binary stars gives a distance to the Large Magellanic Cloud that is precise to one per cent.

Ferroptosis, a form of regulated cell death that is induced by excessive lipid peroxidation, is a key tumour suppression mechanism 1 – 4 . Glutathione peroxidase 4 (GPX4) 5 , 6 and ferroptosis suppressor protein 1 (FSP1) 7 , 8 constitute two major ferroptosis defence systems. Here we show that treatment of cancer cells with GPX4 inhibitors results in acute depletion of N -carbamoyl- l -aspartate, a pyrimidine biosynthesis intermediate, with concomitant accumulation of uridine. Supplementation with dihydroorotate or orotate—the substrate and product of dihydroorotate dehydrogenase (DHODH)—attenuates or potentiates ferroptosis induced by inhibition of GPX4, respectively, and these effects are particularly pronounced in cancer cells with low expression of GPX4 (GPX4 low ). Inactivation of DHODH induces extensive mitochondrial lipid peroxidation and ferroptosis in GPX4 low cancer cells, and synergizes with ferroptosis inducers to induce these effects in GPX4 high cancer cells. Mechanistically, DHODH operates in parallel to mitochondrial GPX4 (but independently of cytosolic GPX4 or FSP1) to inhibit ferroptosis in the mitochondrial inner membrane by reducing ubiquinone to ubiquinol (a radical-trapping antioxidant with anti-ferroptosis activity). The DHODH inhibitor brequinar selectively suppresses GPX4 low tumour growth by inducing ferroptosis, whereas combined treatment with brequinar and sulfasalazine, an FDA-approved drug with ferroptosis-inducing activity, synergistically induces ferroptosis and suppresses GPX4 high tumour growth. Our results identify a DHODH-mediated ferroptosis defence mechanism in mitochondria and suggest a therapeutic strategy of targeting ferroptosis in cancer treatment. DHO dehydrogenase regulates ferroptosis by preventing mitochondrial lipid peroxidation and its inhibition suppresses growth in tumours with low levels of GPX4.

Cellulose is the most abundant polysaccharide on Earth. It can be obtained from a vast number of sources, e.g. cell walls of wood and plants, some species of bacteria, and algae, as well as tunicates, which are the only known cellulose-containing animals. This inherent abundance naturally paves the way for discovering new applications for this versatile material. This review provides an extensive survey on cellulose and its derivatives, their structural and biochemical properties, with an overview of applications in tissue engineering, wound dressing, and drug delivery systems. Based on the available means of selecting the physical features, dimensions, and shapes, cellulose exists in the morphological forms of fiber, microfibril/nanofibril, and micro/nanocrystalline cellulose. These different cellulosic particle types arise due to the inherent diversity among the source of organic materials or due to the specific conditions of biosynthesis and processing that determine the consequent geometry and dimension of cellulosic particles. These different cellulosic particles, as building blocks, produce materials of different microstructures and properties, which are needed for numerous biomedical applications. Despite having great potential for applications in various fields, the extensive use of cellulose has been mainly limited to industrial use, with less early interest towards the biomedical field. Therefore, this review highlights recent developments in the preparation methods of cellulose and its derivatives that create novel properties benefiting appropriate biomedical applications.

The phytohormone salicylic acid (SA) controls biotic and abiotic plant stress responses. Plastid-produced chorismate is a branch-point metabolite for SA biosynthesis. Most pathogen-induced SA derives from isochorismate, which is generated from chorismate by the catalytic activity of ISOCHORISMATE SYNTHASE1. Here, we ask how and in which cellular compartment isochorismate is converted to SA. We show that in Arabidopsis, the pathway downstream of isochorismate requires only two additional proteins: ENHANCED DISEASE SUSCEPTIBILITY5, which exports isochorismate from the plastid to the cytosol, and the cytosolic amidotransferase avrPphB SUSCEPTIBLE3 (PBS3). PBS3 catalyzes the conjugation of glutamate to isochorismate to produce isochorismate-9-glutamate, which spontaneously decomposes into SA and 2-hydroxy-acryloyl-N-glutamate. The minimal requirement of three compartmentalized proteins controlling unidirectional forward flux may protect the pathway against evolutionary forces and pathogen perturbations.

Opioids are the primary drugs used in Western medicine for pain management and palliative care. Farming of opium poppies remains the sole source of these essential medicines, despite diverse market demands and uncertainty in crop yields due to weather, climate change, and pests. We engineered yeast to produce the selected opioid compounds thebaine and hydrocodone starting from sugar. All work was conducted in a laboratory that is permitted and secured for work with controlled substances. We combined enzyme discovery, enzyme engineering, and pathway and strain optimization to realize full opiate biosynthesis in yeast. The resulting opioid biosynthesis strains required the expression of 21 (thebaine) and 23 (hydrocodone) enzyme activities from plants, mammals, bacteria, and yeast itself. This is a proof of principle, and major hurdles remain before optimization and scale-up could be achieved. Open discussions of options for governing this technology are also needed in order to responsibly realize alternative supplies for these medically relevant compounds.

Arbuscular mycorrhizal (AM) fungi facilitate plant uptake of mineral nutrients and draw organic nutrients fromthe plant. Organic nutrients are thought to be supplied primarily in the formof sugars. Here we show that the AM fungus Rhizophagus irregularis is a fatty acid auxotroph and that fatty acids synthesized in the host plants are transferred to the fungus to sustain mycorrhizal colonization. The transfer is dependent on RAM2 (REQUIRED FOR ARBUSCULAR MYCORRHIZATION 2) and the ATP binding cassette transporter–mediated plant lipid export pathway. We further show that plant fatty acids can be transferred to the pathogenic fungus Golovinomyces cichoracerum and are required for colonization by pathogens. We suggest that themutualistic mycorrhizal and pathogenic fungi similarly recruit the fatty acid biosynthesis program to facilitate host invasion.

Bacteria and fungi are used industrially to produce commodity fine chemicals at vast scale. Sugars are an economical feedstock, but many of the desired products require enzymatic reduction, meaning that some of the sugar must be diverted to regenerate the cellular reductant NADPH (reduced form of nicotinamide adenine dinucleotide phosphate). Guo et al. show that electrons from light-sensitive nanoparticles can drive reduction of cellular NADPH in yeast, which can then be used for reductive biosynthetic reactions. This system can reduce diversion of carbon to NADPH regeneration and should be compatible with many existing engineered strains of yeast. Science , this issue p. 813 Light-harvesting nanoparticles power reduction reactions in genetically engineered yeast. Inorganic-biological hybrid systems have potential to be sustainable, efficient, and versatile chemical synthesis platforms by integrating the light-harvesting properties of semiconductors with the synthetic potential of biological cells. We have developed a modular bioinorganic hybrid platform that consists of highly efficient light-harvesting indium phosphide nanoparticles and genetically engineered Saccharomyces cerevisiae , a workhorse microorganism in biomanufacturing. The yeast harvests photogenerated electrons from the illuminated nanoparticles and uses them for the cytosolic regeneration of redox cofactors. This process enables the decoupling of biosynthesis and cofactor regeneration, facilitating a carbon- and energy-efficient production of the metabolite shikimic acid, a common precursor for several drugs and fine chemicals. Our work provides a platform for the rational design of biohybrids for efficient biomanufacturing processes with higher complexity and functionality.

Deepwater rice varieties grow taller when flooded, in a growth response driven by the plant hormones gibberellin and ethylene. This keeps the leaves above the water. Kuroha et al. identified the genes underlying this phenotype, which encode a component of the gibberellin biosynthetic pathway and its regulatory ethylene-responsive transcription factor. This genetic relay drives growth of the plant stem internodes in response to flooding. Modern cultivated deepwater rice, which has been domesticated for adaptation to the monsoon season of Bangladesh, emerged from the genetic variation found in wild rice strains over a broader geographic region. Science , this issue p. 181 Ethylene-inducible activation of gibberellin biosynthesis helps rice survive long periods of submersion in flooded plots. Most plants do poorly when flooded. Certain rice varieties, known as deepwater rice, survive periodic flooding and consequent oxygen deficiency by activating internode growth of stems to keep above the water. Here, we identify the gibberellin biosynthesis gene, SD1 ( SEMIDWARF1 ), whose loss-of-function allele catapulted the rice Green Revolution, as being responsible for submergence-induced internode elongation. When submerged, plants carrying the deepwater rice–specific SD1 haplotype amplify a signaling relay in which the SD1 gene is transcriptionally activated by an ethylene-responsive transcription factor, OsEIL1a. The SD1 protein directs increased synthesis of gibberellins, largely GA 4 , which promote internode elongation. Evolutionary analysis shows that the deepwater rice–specific haplotype was derived from standing variation in wild rice and selected for deepwater rice cultivation in Bangladesh.

Plant derived biogenic synthesis of nanoparticles (NP) has been the recent trend in material science as featured sustainable catalysts. A great deal of the current nanocatalytic research has been oriented on the bio-inspired green catalysts based on their wide applicability. In this context, CuO NPs are synthesized following a green approach using an herbal tea (Stachys Lavandulifolia) flower extract. The phytochemicals contained in it were used asthe internal reductant without applying harsh chemicals or strong heat. The derived nanoparticles also got stabilized by the biomolecular capping. The as-synthesized CuO NPs was characterized over FT-IR, FE-SEM, EDS, TEM, XRD, TGA and UV–Vis spectroscopy. These NPs were exploited as a competent catalyst in the aryl and heteroaryl C–heteroatom (N, O, S) cross coupling reactions affording outstanding yields. The nanocatalyst was isolated and recycled in 8 consecutive runs with reproducible catalytic activity. Rigidity of the CuO/ S. Lavandulifolia nanocomposite was further justified by leaching test and heterogeneity test.

A novel eco-friendly procedure was developed to produce safer, stable and highly pure zinc oxide nanoparticles (ZnO NPs) using microalgae Chlorella extract. The ZnO NPs were synthesized simply using zinc nitrate and microalgae Chlorella extract which conducted at ambient conditions. In this recipe, microalgae Chlorella extract acted as the reducing agent and a stabilizing layer on fresh ZnO NPs. UV–visible spectrum was confirmed the formation of ZnO NPs showing an absorption peak at 362 nm. XRD results demonstrated that prepared ZnO NPs has a high-crystalline hexagonal (Wurtzite) structure, with average size about 19.44 nm in diameter. FT-IR spectral analysis indicated an active contribution of algae-derived biomolecules in zinc ions bioreduction. According to SEM and TEM observations, ZnO NPs are well dispersed and has a hexagonal shape with the average size of 20 ± 2.2 nm, respectively. Based on gas chromatography analyses, the optimum 0.01 g/L dosage of ZnO catalyst revealed an effective photocatalytic activity toward the degradation (97%) of Dibenzothiophene (DBT) contaminant as an organosulfur model in the neutral pH at the mild condition. Rapid separation and facile recyclability at five consecutive runs were demonstrated high efficiency and durability of green ZnO nanophotocatalyst. The possible mechanisms of green ZnO NPs formation and the photo-desulfurization of DBT were also proposed.