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Rong-zi Li,1 Xiao-Wen Ding,1 Thangiah Geetha,1 Layla Al-Nakkash,2 Tom L Broderick,2 Jeganathan Ramesh Babu1 1Department of Nutrition, Dietetics and Hospitality Management, Auburn University, Auburn, AL 36849, USA; 2Department of Physiology, Laboratory of Diabetes and Exercise Metabolism, College of Graduate Studies, Midwestern University, Glendale, AZ 85308, USACorrespondence: Jeganathan Ramesh BabuDepartment of Nutrition, Dietetics and Hospitality Management, Auburn University, Auburn, AL 36849, USATel +1 334 844 3840 Fax +1 334 844 3268Email jeganrb@auburn.eduPurpose: Diabetes mellitus (DM)-induced brain damage is characterized by cellular, molecular and functional changes. The mechanisms include oxidative stress, neuroinflammation, reduction of neurotrophic factors, insulin resistance, excessive amyloid beta (Aβ) deposition and Tau phosphorylation. Both antidiabetic and neuroprotective effects of the phytoestrogen genistein have been reported. However, the beneficial effect of genistein in brain of the ob/ob mouse model of severe obesity and diabetes remains to be determined.Methods: In this study, female ob/ob mice and lean control mice were fed with either a standard diet or a diet containing genistein (600mg/kg) for a period of 4 weeks. Body weight was monitored weekly. Blood was collected for the measurement of glucose, insulin and common cytokines. Mice brains were isolated for Western immunoblotting analyses.Results: Treatment with genistein reduced weight gain of ob/ob mice and decreased hyperglycemia compared to ob/ob mice fed the standard diet. The main findings show that genistein treatment increased insulin sensitivity and the expression levels of the neurotrophic factors nerve growth factor (NGF) and brain-derived neurotrophic factors (BDNF). In these mice, genistein also reduced Aβ deposition and the level of hyper-phosphorylated Tau protein.Conclusion: The results of our study indicate the beneficial effects of genistein in the obesediabetic mousebrain, including improving brain insulin signaling, increasing neurotrophic support, and alleviating Alzheimer’s disease-related pathology.Keywords: isoflavones, leptin-deficient mice, brain injury, insulin signaling, amyloid beta

Table S2. Primers for entire coding exons and intron-exon boundaries of BRCA2. (DOCX 31 kb)

Table S1. Primers for entire coding exons and intron-exon boundaries of BRCA1. (DOCX 30 kb)

Comparing with point source pollution, the non-point source (NPS) one, particularly from agricultural activities, has been dominant in many countries presently, causing nutrient loss, aqueous systems damaging, and eutrophication. One of the key elements responsible for it is nitrogen (N). The Yongding River is an important watershed in North China, which relates to Beijing City (capital of China), Tianjing City and Hebei, Inner Mongolia, Shanxi province. This study, reveals agricultural NPS pollution of Yongding River in Hebei province. The resource, loading and distribution of agricultural NPS pollution are simulated and analyzed in the paper based on remoting sense and geographic information system by export coefficient model (ECM). The result indicates that the total NPS-N loading of the research area was 5.68 × 104 t in 2008. The loading of agricultural landuse was 4.38 × 104 t, and that of rural life and livestock feeding was 0.90 × 104 t and 0.40 × 104 t respectively. As far as the spacial distribution of the loading is concerned, farm lands (sloping areas especially), villages and hoggeries were areas with heavy pollution. In the conclusion, it is suggested that the methods of agricultural landuse and N fertilizer utilization should be improved as well as the treatment efficiency of waster water and solid waste should be increased.