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Background: Approximately 50% of patients harbor the T790M mutation after developing first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance. Evidence has showed the major treatment failure is local relapses and limited metastases. Several studies have demonstrated the value of radiotherapy in metastatic non-small cell lung cancer (NSCLC) with the EGFR T790M mutation after the development of TKI resistance. The aim of this study was to explore the role of radiation in T790M-mutant NSCLC and the value of early radiotherapy for NSCLC with T790M-mediated EGFR-TKI resistance. Methods: Gefitinib-resistant NSCLC cell lines were established via stepwise exposure to increasing concentrations of gefitinib (PC-9-GR). Droplet digital PCR was used to determine the relative T790M subclone abundance. In vitro and in vivo models were established using different mixtures of PC-9-GR and PC-9 cells. Differentially expressed genes were identified using RNA sequencing. Two research models were constructed (salvage and prophylactic radiotherapy) to determine the effects of early radiotherapy on gefitinib-resistant cells. Results: PC-9-GR cells exhibited higher radiosensitivity than PC-9 cells (sensitivity enhancement ratio = 1.5). Salvage radiation reduced the number of T790M-mutant subclones, and the relative T790M abundance was significantly lower than that without radiation at 90 days (10.94% vs. 21.54%). Prophylactic radiation prevented the development of T790M subclones. These results were also confirmed in vivo. qRT-PCR revealed threefold elevation of miR-1243 in PC-9-GR cells, and the increased radiosensitivity of PC-9-GR cells was inhibited when miR-1243 was knocked down. RNA sequencing revealed that SPOCK1 was downregulated in PC-9-GR cells. Interestingly, bioinformatic analysis showed that SPOCK1 was a target gene of miR-1243. SPOCK1 knockdown markedly increased the radiosensitivity of PC-9 cells. Conclusion: Gefitinib-resistant NSCLC with the T790M mutation had higher radiosensitivity than that without the mutation, possibly mediated by SPOCK1. Early radiotherapy can eliminate T790M subclones, providing evidence for the benefit of early local treatment in patients with TKI-resistant NSCLC.
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As it is central to sustainable urban development, urban mobility has primarily been scrutinised for its scaling and hierarchical properties. However, traditional analyses frequently overlook spatial directionality, a critical factor in city centre congestion and suburban development. Here, we apply vector computation to unravel the spatial directionality of urban mobility, introducing a two-dimensional anisotropy-centripetality metric. Utilising travel data from 90 million mobile users across 60 Chinese cities, we effectively quantify mobility patterns through this metric, distinguishing between strong monocentric, weak monocentric, and polycentric patterns. Our findings highlight a notable difference: residents in monocentric cities face increasing commuting distances as cities expand, in contrast to the consistent commuting patterns observed in polycentric cities. Notably, mobility anisotropy intensifies in the outskirts of monocentric cities, whereas it remains uniform in polycentric settings. Additionally, centripetality wanes as one moves from the urban core, with a steeper decline observed in polycentric cities. Finally, we reveal that employment attraction strength and commuting distance scaling are key to explaining these divergent urban mobility patterns. These insights are important for shaping effective policies aimed at alleviating congestion and guiding suburban housing development.
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Next-generation high-temperature applications increasingly rely heavily on advanced thermistor materials with enhanced thermal stability and electrical performance. However, thus far, the great challenge of realizing high thermal stability and precision in a wide temperature range has become a key bottleneck restricting the high-temperature application. Here, we propose a high-entropy strategy to design novel high-temperature thermistor ceramics (La0.2Ce0.2Nd0.2Sm0.2Eu0.2)NbO4. Differences in atomic size, mass, and electronegativity in this high-entropy system cause high lattice distortion, substantial grain boundaries, and high dislocation density. These enhance the charge carrier transport and reduce the grain boundary resistance, thus synergistically broadening the temperature range. Our samples maintain high precision and thermal stability over a wide temperature range from room temperature to 1523 K (ΔT = 1250 K) with an aging value as low as 0.42% after 1000 h at 1173 K, showing breakthrough progress in high-temperature thermistor ceramics. This study establishes an effective approach to enhancing the performance of high-temperature thermistor materials through high-entropy strategies.
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Flexible electronics is an emerging and cutting-edge technology which is considered as the building blocks of the next generation micro-nano electronics. Flexible electronics integrate both active and passive functions in devices, driving rapid developments in healthcare, the Internet of Things (IoT), and industrial fields. Among them, flexible temperature sensors, which can be directly attached to human skin or curved surfaces of objects for continuous and stable temperature measurement, have attracted much attention for applications in disease prediction, health monitoring, robotic signal sensing, and curved surface temperature measurement. Preparing flexible temperature sensors with high sensitivity, fast response, wide temperature measurement interval, high flexibility, stretchability, low cost, high reliability, and stability has become a research target. This article reviewed the latest development of flexible temperature sensors and mainly discusses the sensitive materials, working mechanism, preparation process, and the applications of flexible temperature sensors. Finally, conclusions based on the latest developments, and the challenges and prospects for research in this field are presented.
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Knowing how workers return to work is a key policymaking issue for economic recovery in the post-COVID-19 era. This paper uses country-wide time-series mobile phone big data (comparing monthly and annual figures), obtained between February 2019 and October 2019 and between February 2020 and October 2020, to discover the spatial patterns of rural migrant workers' (RMWs') return to work in China's three urban agglomerations (UAs): the Beijing-Tianjin-Hebei Region, the Yangtze River Delta and the Pearl River Delta. Spatial patterns of RMWs' return to work and how these patterns vary with location, city level and human attribute were investigated using the fine-scale social sensing related to post-pandemic human mobility. The results confirmed the multidimensional spatiotemporal differentiations, interaction effects between variable pairs and effects of the actual situation on the changing patterns of RMWs' return to work. The spatial patterns of RMWs' return to work in China's major three UAs can be regarded as a comprehensive and complex interaction result accompanying the nationwide population redistribution, which was affected by various hidden factors. Our findings provide crucial implications and suggestions for data-informed policy decisions for a harmonious society in the post-COVID-19 era.