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Integrated photonic source of Gottesman–Kitaev–Preskill qubits
Acetolysis for epoxy-amine carbon fibre-reinforced polymer recycling
Author Correction: Methane oxidation to ethanol by a molecular junction photocatalyst
Targeting PIKfyve-driven lipid metabolism in pancreatic cancer
Abstract Pancreatic ductal adenocarcinoma (PDAC) subsists in a nutrient-deregulated microenvironment, making it particularly susceptible to treatments that interfere with cancer metabolism 1,2 . For example, PDAC uses, and is dependent on, high levels of autophagy and other lysosomal processes 3–5 . Although targeting these pathways has shown potential in preclinical studies, progress has been hampered by the difficulty in identifying and characterizing favourable targets for drug development 6 . Here, we characterize PIKfyve, a lipid kinase that is integral to lysosomal functioning 7 , as a targetable vulnerability in PDAC. Using a genetically engineered mouse model, we established that PIKfyve is essential to PDAC progression. Furthermore, through comprehensive metabolic analyses, we found that PIKfyve inhibition forces PDAC to upregulate a distinct transcriptional and metabolic program favouring de novo lipid synthesis. In PDAC, the KRAS–MAPK signalling pathway is a primary driver of de novo lipid synthesis. Accordingly, simultaneously targeting PIKfyve and KRAS–MAPK resulted in the elimination of the tumour burden in numerous preclinical human and mouse models. Taken together, these studies indicate that disrupting lipid metabolism through PIKfyve inhibition induces synthetic lethality in conjunction with KRAS–MAPK-directed therapies for PDAC.
Revealed: how the brain turns stress into a bad night’s sleep
Daily briefing: Some moths can navigate using starlight
Author Correction: Deterministic and reconfigurable graph state generation with a single solid-state quantum emitter
Single-celled organisms set for greater role in gut health
Delivering equity in low-carbon multisector infrastructure planning
Abstract Many countries worldwide are transitioning from fossil fuel-dependent economies to carbon neutrality, driven by the 2030 agenda for sustainable development and the Paris Agreement. However, without considering the regional distribution of essential services like water and energy, this transition could inadvertently maintain or increase inequities, threatening sustainable development. Here, we argue that spatial equity of benefits should be considered in planning low-carbon energy transitions, especially in developing countries with multisector interdependencies and high service disparities between regions. We propose an analytical framework that can help analysts and policymakers plan for regionally equitable climate-compatible futures. The multisector design framework combines integrated river basin-power system simulation with artificial intelligence design tools. The utility of the framework is demonstrated for Ghana by identifying the most efficient infrastructure intervention portfolios and their implied trade-offs between spatial equity in water and energy service provision, carbon emissions, food production, and river ecosystem performance. Case-study results show that an equitable low-carbon energy transition will require increased investments in renewable energy and transmission alongside more informed infrastructure system planning. With low renewable investments, equity can be improved, but at the cost of higher emissions and electricity supply curtailments.