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Strategies beyond hormone-related therapy need to be developed to improve prostate cancer mortality. Here, we show that FUBP1 and its methylation were essential for prostate cancer progression, and a competitive peptide interfering with FUBP1 methylation suppressed the development of prostate cancer. FUBP1 accelerated prostate cancer development in various preclinical models. PRMT5-mediated FUBP1 methylation, regulated by BRD4, was crucial for its oncogenic effect and correlated with earlier biochemical recurrence in our patient cohort. Suppressed prostate cancer progression was observed in various genetic mouse models expressing the FUBP1 mutant deficient in PRMT5-mediated methylation. A competitive peptide, which was delivered through nanocomplexes, disrupted the interaction of FUBP1 with PRMT5, blocked FUBP1 methylation, and inhibited prostate cancer development in various preclinical models. Overall, our findings suggest that targeting FUBP1 methylation provides a potential therapeutic strategy for prostate cancer management., Introduction Prostate cancer is a major global health care challenge (1, 2). Androgens from the testis and the adrenal gland bind to androgen receptor (AR) to activate AR signaling and [...]

[Objective] The ecological effect of urban spatial expansion is the key problem of human-environment relationship in the process of urbanization. It is of great significance to explore the complex scientific problem of ecological effect caused by urban spatial expansion from multiple angles to promote the sustainable and high-quality development of urban and ecological space. [Methods] Taking the main urban area of Lanzhou City in China as an example, this study calculated the scale, intensity, and landscape pattern indices of urban spatial expansion in 1995, 2005, 2015, and 2020 to reflect the spatiotemporal variation characteristics of urban spatial expansion in the city from 1995 to 2020, and divided the research area into 12184 grids. Using the spatial principal component analysis method, atmospheric radiation transfer equation method, and revised ecosystem service value estimation model, this study analyzed the ecological risk effect, heat island effect, and ecosystem service effect of urban spatial expansion from various angles, and discussed the impact of natural environment conditions on the ecological effect of urban spatial expansion of cities in river valleys. [Results] The results show that from 1995 to 2020, the scale and intensity of urban expansion in Lanzhou City have increased, the fragmentation of urban landscape has decreased, urban expansion has mainly occurred in the western and northern parts of the city, and the urban expansion mode has changed from group expansion to leaping expansion. The overall ecological risk effect and heat island effect in the city have shown a weakening trend, but a rising trend was observed in the river valley, and the overall pattern of effects has been characterized by high in the valley and low at the peripheries. There is a slight improvement in the ecosystem service effect, which mainly shows that the ecosystem service value in the surrounding areas of the river valley has improved significantly, and some areas in the built-up area have changed from low-value area to medium-value area. Urban expansion negatively affects the natural substrates of the region, while the natural substrates also affects the scale, direction, and mode of urban expansion. Coordinating the relationship between the two is essential for the sustainable and harmonious development of human beings and nature. [Conclusion] The research framework of ecological effects of urban spatial expansion was constructed from multiple perspectives. Urban spatial expansion has a significant impact on ecological risk, heat island, and ecosystem service effects at the grid scale, which provides a new way of quantitative visualization of the dynamic relationships between urban evolution and ecological environment.

This study presents an analysis of daily temperature and precipitation extremes with return periods ranging from 2 to 50 years in phase 6 of the Coupled Model Intercomparison Project (CMIP6) multimodel ensemble of simulations. Judged by similarity with reanalyses, the new-generation models simulate the present-day temperature and precipitation extremes reasonably well. In line with previous CMIP simulations, the new simulations continue to project a large-scale picture of more frequent and more intense hot temperature extremes and precipitation extremes and vanishing cold extremes under continued global warming. Changes in temperature extremes outpace changes in global annual mean surface air temperature (GSAT) over most landmasses, while changes in precipitation extremes follow changes in GSAT globally at roughly the Clausius-Clapeyron rate of;7% 8C21. Changes in temperature and precipitation extremes normalized with respect to GSAT do not depend strongly on the choice of forcing scenario or model climate sensitivity, and do not vary strongly over time, but with notable regional variations. Over the majority of land regions, the projected intensity increases and relative frequency increases tend to be larger for more extreme hot temperature and precipitation events than for weaker events. To obtain robust estimates of these changes at local scales, large initial-condition ensemble simulations are needed. Appropriate spatial pooling of data from neighboring grid cells within individual simulations can, to some extent, reduce the needed ensemble size.

Strategies for patient stratification and early intervention are required to improve clinical benefits for patients with prostate cancer. Here, we found that active DHEA utilization in the prostate gland correlated with tumor aggressiveness at early disease stages, and 3[beta]HSD1 inhibitors were promising for early intervention. [[sup.3]H]-labeled DHEA consumption was traced in fresh prostatic biopsies ex vivo. Active DHEA utilization was more frequently found in patients with metastatic disease or therapy-resistant disease. Genetic and transcriptomic features associated with the potency of prostatic DHEA utilization were analyzed to generate clinically accessible approaches for patient stratification. UBE3D, by regulating 3[beta]HSD1 homeostasis, was discovered to be a regulator of patient metabolic heterogeneity. Equilin suppressed DHEA utilization and inhibited tumor growth as a potent 3[beta]HSD1 antagonist, providing a promising strategy for the early treatment of aggressive prostate cancer. Overall, our findings indicate that patients with active prostatic DHEA utilization might benefit from 3[beta]HSD1 inhibitors as early intervention., Introduction Prostate cancer is the most common cancer malignancy in men in Western countries, and its incidence is increasing rapidly in China (1, 2). Therapy resistance is inevitable due to [...]