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• Sobol' method is used to evaluate the sensitivity of APSIM-Wheat yield predictions. • Yield is most sensitive to initial nitrogen amount, soil parameters, precipitation. • Estimated yield is influenced most by the limiting resource under given conditions. • Scenarios for high fertilization level or dry seasons have lower yield variability. The performance of cropping system models is often limited by uncertainties in model parameters and inputs. This study aims to explore how model yield prediction responds to these uncertainties under various environmental and management conditions. The Sobol' method was used to investigate the sensitivity of the Agricultural Production Systems SIMulator (APSIM)-Wheat yield prediction to the following factors: air temperature (maximum and minimum), precipitation, initial soil nitrogen content, nitrogen fertilization amount, and soil hydraulic parameters. Eighteen scenarios were defined to consider a combination of three weather conditions (wet, normal, and dry growing season, based on the historical climatology of the Wimmera district of Victoria, Australia), three soil types (sandy, loamy, and clayey soils), and two nitrogen fertilization applications (50 and 100 kg N/ha). Eight thousand APSIM simulations were used to calculate the first order and total sensitivity indices for each scenario. The effects of weather, soil water characteristics and nitrogen availability were estimated by measuring their impacts on sensitivity indices. Our results show that yield was more sensitive either to variables that control water availability (precipitation and soil type) or variables that control nitrogen availability, depending on which was more limiting to wheat growth under the scenario. For example, in case of low nitrogen fertilization scenario, the initial nitrogen content sensitivity ranked first. Variation of this factor contributed 64% to 79% to the variance in simulated yield for clayey soils, nearly four times higher than the second-ranked factor (nitrogen fertilization amount). Soil hydraulic parameters and precipitation were most important when the crop growth was more constrained by water availability than by nitrogen availability. In the case of sandy soils in dry years with high nitrogen fertilization level, soil parameters and precipitation accounted for 83% of the yield variability. Minimum temperature consistently ranked as the least important factor under all scenarios. This work will help researchers better understand the model inputs' impacts on the simulated yield variability under various soil, management, and weather conditions. The results also support agronomists and practitioners in the optimal use of the APSIM-Wheat model as a management tool. [Display omitted] [ABSTRACT FROM AUTHOR]

Farm-level seasonal irrigation water usage is often highly variable across time and space in an irrigation district. Identifying the driving factors of this variation can help researchers and managers understand the underlying efficiency of water usage, identify the sources of water waste and develop best irrigation practices to facilitate the development of more efficient and sustainable irrigated cropping systems. This study explored driving factors for the seasonal irrigation water usage across an irrigation district in south-eastern Australia, using extensive climate, soil, cropping and water use data from 312 farms (a total of 1099 annual crop water use records). It focused on three irrigated crops (corn/maize, cotton and rice) for 2011–2019. Factors considered included climate, soils, irrigation practices and water allocation, from which key driving factors and their effects on the seasonal irrigation water usage were identified. A Bayesian hierarchical model averaging approach was developed to determine key predictors and estimate seasonal irrigation water usage. The Bayesian hierarchical modelling framework allowed seasonal irrigation water usage to be estimated at all crop-farm-year observation points simultaneously while also enabling different key predictors to be selected for different crop types. Results showed that the seasonal irrigation water usage was mainly driven by irrigation practices and soil, but the water use of different crop types was driven by different subsets of irrigation and soil predictors. Modelling was undertaken in natural log space and the model showed reasonable accuracy in estimating the seasonal irrigation water usage (R2 = 0.62). Our model is considered useful in 1) identifying drivers of variation of the seasonal irrigation water usage across time and space, and 2) suggesting potential adjustments to irrigation practices and quantifying their benefits to reduce irrigation water usage. • Factors driving seasonal irrigation usage were explored in an irrigation district. • A Bayesian hierarchical model (BHM) was developed for 1099 crop water use records. • Seasonal irrigation usage was mainly influenced by soil and irrigation practices. • The BHM showed good accuracy in estimating seasonal irrigation usage (R2 = 0.62). [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide. Targeted therapy against the epidermal growth factor receptor (EGFR) is a promising treatment approach for NSCLC. However, resistance to EGFR tyrosine kinase inhibitors (TKIs) remains a major challenge in its clinical management. EGFR mutation elevates the expression of hypoxia-inducible factor-1 alpha to upregulate the production of glycolytic enzymes, increasing glycolysis and tumor resistance. The inhibition of glycolysis can be a potential strategy for overcoming EGFR-TKI resistance and enhancing the effectiveness of EGFR-TKIs. In this review, we specifically explored the effectiveness of pyruvate dehydrogenase kinase inhibitors and lactate dehydrogenase A inhibitors in combating EGFR-TKI resistance. The aim was to summarize the effects of these natural products in preclinical NSCLC models to provide a comprehensive understanding of the potential therapeutic effects. The study findings suggest that natural products can be promising inhibitors of glycolytic enzymes for the treatment of EGFR-TKI-resistant NSCLC. Further investigations through preclinical and clinical studies are required to validate the efficacy of natural product-based glycolytic inhibitors as innovative therapeutic modalities for NSCLC. [ABSTRACT FROM AUTHOR]