We demonstrated that FO exhibits an anti-diabetic effect mainly through attenuation of β-cell death, thereby elevating insulin synthesis by upregulating PDX-1 and GLP1-R via a Sirt-1-dependent manner. Therefore, FO-containing food or supplements may have a therapeutic effect for diabetes by preventing β-cell damage and dysfunction.
Proper amounts of copper supplemented in livestock feed improve the physical growth and traits of farm animals. The pancreas is an important organ with both exocrine and endocrine portions. To investigate the role and mechanism of copper in the sheep pancreas, we first established sheep pancreatic duct organoids (sPDOs). We found that an appropriate amount of copper benefited the formation and growth of sPDOs, whereas excess or deficient copper damaged sPDOs. We found that the proliferation-stimulating effect of copper was related to the copper chaperone antioxidant protein 1 (ATOX1)-dependent activation of MEK-ERK1/2 signaling. Atox1 knockdown suppressed the cell proliferation of sPDOs, even in the presence of the MEK activator. These results indicate that moderate concentrations of copper promote sPDO growth through ATOX1-regulated cell proliferation by activation of MEK-ERK. Moreover, our study indicates that organoids may be a useful model to study organ growth mechanisms in livestock.
Diabetes mellitus is characterized by pancreatic β cell dysfunction. Previous studies have indicated that epidermal growth factor (EGF) and microRNA-124a (miR-124a) play opposite roles in insulin biosynthesis and secretion by beta cells. However, the underlying mechanisms remain poorly understood. In the present study, we demonstrated that EGF could inhibit miR-124a expression in beta cell lines through downstream signaling pathways, including mitogen-activated protein kinase kinase (MEK) and phosphatidylinositol 3-kinase (PI3K) cascades. Further, the transcription factor ETS2, a member of the ETS (E26 transformation-specific) family, was identified to be responsible for the EGF-mediated suppression of miR-124a expression, which was dependent on ETS2 phosphorylation at threonine 72. Activation of ETS2 decreased miR-124a promoter transcriptional activity through the putative conserved binding sites AGGAANA/TN in three miR-124a promoters located in different chromosomes. Of note, ETS2 played a positive role in regulating beta cell function-related genes, including miR-124a targets, Forkhead box a2 (FOXA2) and Neurogenic differentiation 1 (NEUROD1), which may have partly been through the inhibition of miR-124 expression. Knockdown and overexpression of ETS2 led to the prevention and promotion of insulin biosynthesis respectively, while barely affecting the secretion ability. These results suggest that EGF may induce the activation of ETS2 to inhibit miR-124a expression to maintain proper beta cell functions and that ETS2, as a novel regulator of insulin production, is a potential therapeutic target for diabetes mellitus treatment.
The research on international trade competitiveness is progressing continuously. Environmental factors have been gradually considered in the competitiveness of international trade. However, the green assessment system of international trade competitiveness is not perfect. Building a model based on the trade economy is complex. This study combines environmental pollution data based on the forest processing industry with trade flows. Environmental trade competitiveness, pollution treatment, and trade scale were selected as the three criterion levels to construct an assessment system. The weight and score of each index were calculated by the overall entropy method. The overall entropy method is more comprehensive than the traditional entropy weight method due to introduce longitudinal comparisons of time and category. This method is a dynamic evaluation model with analysis of three-dimensional sequential data tables. The use of this method enables the assessment model to analyze more comprehensively the green level of a country’s trade in wooden forest products in terms of time and product category. The green level of chemical wood pulp and sawn timber trade in China is at a high level. The pollution treatment and trade scale of chemical wood pulp and sawn timber attained a medium level of matching. The trades in particle board, hardboard, newsprint, carton board, and wrapping paper are at medium levels of green. The trades in medium density fiberboard and plywood have poor levels of green and need to improve their green production capacity. It is suggested that China should increase investment in scientific research, as well as establish policies to restrict and treat pollution in the industry of wooden forest products, while increasing the export volumes of products with high added value. China should attach importance to the pollution resulting from the manufacture of wooden forest products. The state should support policies for these producers reducing production emissions.
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