Historical trends of breast cancer burden attributable to metabolic factors among Chinese women, 1990-2019: A population-based epidemiological study.

BACKGROUND:  This study aims to analyze breast cancer burden attributable to high body mass index (BMI) and high fasting plasma glucose (FPG) in China from 1990 to 2019. METHODS: Data were obtained from the Global Burden of Disease (GBD) study 2019. Deaths and disability-adjusted life years (DALYs) were used for attributable burden, and age-period-cohort (APC) model was used to evaluate the independent effects of age, period and birth cohort. RESULTS: In 2019, the age-standardized mortality and DALY rates of breast cancer attributable to high BMI were 1.107 (95% UI: 0.311, 2.327) and 29.990 (8.384, 60.713) per 100 000, and mortality and DALY rates attributable to high FPG were 0.519 (0.095, 1.226) and 13.662 (2.482, 32.425) per 100 000. From 1990 to 2019, the age-standardized mortality and DALY rates of breast cancer attributable to high BMI increased by 1.192% and 1.180%, and the trends of high FPG were not statistically significant. The APC results showed that the age effects of high BMI and high FPG-mortality and DALY rates increased, with the highest rates in the age group over 80 years. The birth cohort effects of high BMI showed "inverted V" shapes, while high FPG showed downward trends. CONCLUSIONS: Age was the main reason for the increase of attributable burden, and postmenopausal women were the high-risk groups. Therefore, targeted prevention measures should be developed to improve postmenopausal women's awareness and effectively reduce the prevalence of obesity and diabetes, thereby reducing the breast cancer burden caused by metabolic factors in China.

Induced differentiation of primordial germ cell like cells from SOX9+ porcine skin derived stem cells.

Understanding the mechanisms behind porcine primordial germ cell like cells (pPGCLCs) development, differentiation, and gametogenesis is crucial in the treatment of infertility. In this study, SOX9+ skin derived stem cells (SOX9+ SDSCs) were isolated from fetal porcine skin and a high-purity SOX9+ SDSCs population was obtained. The SOX9+ SDSCs were induced to transdifferentiate into PGCLCs during 8 days of cultured. The results of RNA-seq, western blot and immunofluorescence staining verified SDSCs have the potential to transdifferentiate into PGCLCs from aspects of transcription factor activation, germ layer differentiation, energy metabolism, and epigenetic changes. Both adherent and suspended cells were collected. The adherent cells were found to be very similar to early porcine primordial germ cells (pPGCs). The suspended cells resembled late stage pPGCs and had a potential to enter meiotic process. This SDSCs culture-induced in vitro model is expected to provide suitable donor cells for stem cell transplantation in the future.

Cross-species analysis of transcriptome emphasizes a critical role of TNF-α in mediating MAP2K7/AKT2 signaling in zearalenone-induced apoptosis.

Zearalenone (ZEN) is a widespread and transgenerational toxicant that can cause serious reproductive health risks, which poses a potential threat to global agricultural production and human health; its estrogenic activity can lead to reproductive toxicity through the induction of granulosa cell apoptosis. Herein, comparative transcriptome analysis, single-cell transcriptome analysis, and weighted gene co-expression network analysis (WGCNA) combined with gene knockout in vivo and RNA interference in vitro were used to comprehensively describe the damage caused by ZEN exposure on ovarian granulosa cells. Comparative transcriptome analysis and WGCNA suggested that the tumor necrosis factor (TNF)-α-mediated mitogen-activated protein kinase 7 (MAP2K7)/ AKT serine/threonine kinase 2 (AKT2) axis was disordered after ZEN exposure in porcine granulosa cells (pGCs) and mouse granulosa cells (mGCs). In vivo gene knockout and in vitro RNA interference verified that TNF-α-mediated MAP2K7/AKT2 was the guiding signal in ZEN-induced apoptosis in pGCs and mGCs. Moreover, single-cell transcriptome analysis showed that ZEN exposure could induce changes in the TNF signaling pathway in offspring. Overall, we concluded that the TNF-α-mediated MAP2K7/AKT2 axis was the main signaling pathway of ZEN-induced apoptosis in pGCs and mGCs. This work provides new insights into the mechanism of ZEN toxicity and provides new potential therapeutic targets for the loss of livestock and human reproductive health caused by ZEN.