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Macrophages perform key functions in tissue homeostasis that are influenced by the local tissue environment. Within the tumor microenvironment, tumor-associated macrophages can be altered to acquire properties that enhance tumor growth. Here, we found that lactate, a metabolite found in high concentration within the anaerobic tumor environment, activated mTORC1 that subsequently suppressed TFEB-mediated expression of the macrophage- specific vacuolar ATPase subunit ATP6V0d2. [Atp6v0d2.sup.-/-] mice were more susceptible to tumor growth, with enhanced HIF-2[alpha]-mediated VEGF production in macrophages that display a more protumoral phenotype. We found that ATP6V0d2 targeted HIF-2[alpha] but not HIF-1[alpha] for lysosome-mediated degradation. Blockade of HIF-2[alpha] transcriptional activity reversed the susceptibility of [Atp6v0d2.sup.-/-] mice to tumor development. Furthermore, in a cohort of patients with lung adenocarcinoma, expression of ATP6V0d2 and HIF-2[alpha] was positively and negatively correlated with survival, respectively, suggesting a critical role of the macrophage lactate/ ATP6V0d2/HIF-2[alpha] axis in maintaining tumor growth in human patients. Together, our results highlight the ability of tumor cells to modify the function of tumor-infiltrating macrophages to optimize the microenvironment for tumor growth., Introduction Macrophages are key regulators of tissue homeostasis and perform tissue-specific functions, which may be influenced by the local tissue environment (1,2). The tumor microenvironment (TME) is generated by a [...]

To investigate the suitable single seed precision sowing density in medium and high-yield drylands and provide a theo- retical basis for high-yield and high-efficiency cultivation in peanut, the overyielding mechanism of single seed precision sowing was studied by analyzing the differences of individual and population quality and nutrient absorption under different single seed precision sowing planting densities of peanut in medium and high-yield drylands. High-yield drylands were selected in Pingdu (PD) of Shandong province and middle drylands were selected in Jiyang (JY) of Shandong province for field experiments in 2018 and 2019. Three single seed precision sowing density treatments were established. Compared with the double-seed sowing (278,000 plants hm-2, DS18.0, CK), three single seed precision sowing treatments were 278,000 plants hm--2 (SS9.0), 238,000 plants hm--2 (SS10.5), and 208,000 plants hm-2 (SS12.0), respectively. Plant spacing of single seed sowing of SS9.0, SS10.5, and SS12.0 treat- ments in peanut was 9.0, 10.5, and 12.0 cm, and plant spacing of double-seed sowing of DS18.0 treatment in peanut was 18.0 cm. The results showed that compared with double seed sowing treatment (DS18.0), single seed precision sowing cultivation improved leaf SPAD, net photosynthetic rate, leaf area index (LAI), the peak value, and duration of leaf area index were higher. Single seed precision sowing exerted the potential of single plant dry matter production, increased the maximum accumulation rate of popula- tion dry matter by 6.1% to 20.7%, and realized the rapid accumulation of dry matter. For high-yield drylands in Pingdu, the popu- lation dry matter accumulation was SS12.0>SS9.0>SS10.5>DS18.0 at mature stage, and that was SS9.0>SS12.0>SS10.5>DS18.0 under middle-yield dryland in Jiyang. Compared with DS18.0, the population dry matter accumulation of single seed sowing cultivation increased by 5.4%-14.9%. Single seed precision sowing cultivation promoted the absorption and the accumulation of N, P, K, and Ca of individual plants and population plants, and increased the distribution ratio of N and P nutrients to pods, and improved fertilizer utilization efficiency. For high-yield drylands, by increasing individual productivity and increasing the number of full fruits and 100-fruit weight per plant, single seed precision sowing had achieved population yield increase of 13.6%-19.1% (2018) and 15.5%-23.8% (2019), and the suitable single seed precision sowing density was 208,000 plants hm-2. In the middle yield dryland, single seed precision sowing promoted individual fitness and formed the population advantage of high density, which was the key effect to increase production with an increase of 8.4%-19.4% (2018) and 13.9%-27.8% (2019), and the suitable density was 278,000 plants hm-2. In conclusion, the population quality and nutrient absorption of high-yield drylands were better than that of middle-yield drylands. The single-seed precision seeding cultivation model can make full use of the production potential of a single plant for medium and high-yield drylands in peanut, promote the accumulation of photosynthetic product and the absorption and utilization of nutrients, and consequently improve the quality of peanuts in both medium and high-yield drylands. This mechanism was characterized by "strong source", "smooth flow", and "large sink". Therefore, this method could help to increase the pod yield and harvest index, and realize the high yield and high efficiency of peanut. [ABSTRACT FROM AUTHOR]