Comprehensive assessment of cellular senescence in the tumor microenvironment.

Cellular senescence (CS), a state of permanent growth arrest, is intertwined with tumorigenesis. Due to the absence of specific markers, characterizing senescence levels and senescence-related phenotypes across cancer types remain unexplored. Here, we defined computational metrics of senescence levels as CS scores to delineate CS landscape across 33 cancer types and 29 normal tissues and explored CS-associated phenotypes by integrating multiplatform data from ~20 000 patients and ~212 000 single-cell profiles. CS scores showed cancer type-specific associations with genomic and immune characteristics and significantly predicted immunotherapy responses and patient prognosis in multiple cancers. Single-cell CS quantification revealed intra-tumor heterogeneity and activated immune microenvironment in senescent prostate cancer. Using machine learning algorithms, we identified three CS genes as potential prognostic predictors in prostate cancer and verified them by immunohistochemical assays in 72 patients. Our study provides a comprehensive framework for evaluating senescence levels and clinical relevance, gaining insights into CS roles in cancer- and senescence-related biomarker discovery.

Impact of Economic Development Level and Agricultural Water Use on Agricultural Production Scale in China.

The change of agricultural production scale is directly related to food security and the stable development of social economy. Particularly, the influence of economic development level and agricultural water use on agricultural production scale cannot be ignored. Therefore, this paper uses the fully modified ordinary least squares (FMOLS) and the Dumitrescu-Hurlin panel causality test models to discuss the effects of the level of economic development, agricultural water use, the level of urbanization, and the market price of agricultural products on the scale of agricultural production in China. The analysis results indicated that agricultural water use, the level of urbanization, and the market price of agricultural products promoted an increase of the scale of agricultural production at the total sample level; a 1% increase for these three variables will result in an increase of the scale of agricultural production of 0.634%, 0.377%, and 0.292%, respectively. The influence of economic development level on agricultural production scale accords with Kuznets curve. However, at the regional level, the influence of each variable on the eastern region is consistent with the trend of the total sample. In the central region, the impact of economic development on agricultural production scale shows a U-shaped curve, and the improvement of urbanization level inhibits the expansion of agricultural production scale. In the western region, all variables failed to pass the significance test. The results of the FMOLS model were validated by the fixed effects model. The results of causality tests showed that bidirectional causality existed between the scale of agricultural production and the level of economic development, the scale of agricultural production and agricultural water use, the level of economic development and the market price of agricultural products, and the level of urbanization and the market price of agricultural products. In different regions, there were differences in causality between variables. Therefore, based on the empirical results, we put forward some policy suggestions to maintain the scale of agricultural production.

Metabolomics strategy reveals therapeutical assessment of limonin on nonbacterial prostatitis.

Limonin has been found to possess significant anti-inflammatory properties in animal tests and with, human cells, however, its precise metabolism mechanism has not been well explored. The aim of this study was to investigate the anti-inflammatory effects of limonin in a nonbacterial prostatitis (NBP) animal model. Global metabolite profiling was performed by ultra-high-performance liquid chromatography combined with time-of-flight mass spectrometry (UPLC/ESI-TOFMS) and in conjunction with multivariate data analysis and pathway analysis which were integrated to explore differentiating metabolites and clarify the mechanism of limonin against capsaicin-induced NBP. Limonin has a potential protective function revealed by the metabolic profiling of limonin-treated rats located closer to the normal group. Twenty potential biomarker candidates and several key metabolic pathways contributing to the treatment of NBP were discovered and identified. Among the pathways, the related glycine, serine and threonine metabolism, glycerophospholipid metabolism were acutely perturbed. The changes in metabolites were restored to their base-line levels after limonin treatment, which might be through regulating the perturbed pathways to the normal state. The results indicate that changed biomarkers and pathways may provide evidence and insight into limonin action mechanisms and enable us to increase research productivity toward metabolomics in therapeutical assessment and drug discovery.