Amelioration of Cholesterol Rich diet-induced Impaired Cognition in AD Transgenic Mice by an LXR Agonist TO901317 Is Associated with the Activation of the LXR-ß-RXR-α-ABCA1 Transmembrane Transport System and Improving the Composition of Lipid Raft.

BACKGROUND: It has been reported that LXR agonist can inhibit Aß generation and alleviate Aß-induced various adverse reactions in vivo and in vitro experiments, but the mechanisms have not been clarified. The study aimed to observe the effect of LXR agonist TO901317 on the cognitive function of AD transgenic mice fed with cholesterol-rich diet (CRD), and to explore the possible mechanism. Methods: 32 male 6-month-old double transgenic AD mice were enrolled and randomly divided into 4 groups: control (normal diet) group, CRD treatment group, TO901317 treatment group and GSK2033 treatment group. After 3 month, Morris water maze was for the changes of spatial exploration and memory ability; ELISA was for detecting the production of Aß42 in the brain; the concentration of total cholesterol (TC), low density lipoprotein (LDL) and high density lipoprotein (HDL) in serum were detected by cholesterol enzyme colorimetry; Finally, the expression of LXR-ß, RXR-α, ABCA1, caveolin-1, BACE1 and APP at protein level in the brains was measured by Western blotting. RESULTS: Compared with the control group, the learning, memory ability and spatial exploration ability of the mice were more significantly serious in the CRD group (P<0.05); The contents of TC and LDL in the serum and the production of Aß42 in the brains were significantly increased (P<0.05), but HDL was remarkably decreased (P<0.05); The protein levels of LXR-ß, RXR-α and ABCA1 were also significantly decreased (P<0.05); The expression of caveolin-1, APP and BACE1 were evidently increased (P<0.05). However, after treatment with TO901317, the impaired learning and memory and spatial exploration ability of the mice were significantly improved (P<0.05); The contents of TC and LDL in serum and the production of Aß42 in the brains were significantly decreased (P<0.05), but HLD was increased (P<0.05); The protein levels of LXR-ß, RXR-α, ABCA1were all significantly increased (P<0.05), while, the expression of caveolin-1, APP and BACE1 were all significantly decreased (P<0.05). All the changes were reversed by GSK2033 (P<0.05). CONCLUSIONS: TO901317 attenuated the more serious impairment of spatial exploration, learning and memory in transgenic AD mice induced by CRD, and the mechanism may be that TO901317 could activate the LXR-ß/RXR-α/ABCA1 transmembrane transport system, promote the cholesterol efflux, and decreased caveolin-1, APP and BACE1, further reduce Aß42 in the brains.

A model based on endorectal ultrasonography predicts lateral lymph node metastasis in low and middle rectal cancer.

PURPOSE: To investigate the risk factors for lymph node (LN) metastasis in low and middle rectal tumors, construct a predictive model and test the model's diagnostic efficacy. METHODS: The clinical and pathological data of 172 patients with rectal cancer confirmed by surgery were retrospectively evaluated, among whom 61 patients were finally included in this study. Patients were divided into positive groups and negative groups based on LN metastasis, and risk factors that might affect LN metastasis were analyzed. Finally, a risk predictive model was constructed based on the weights of each risk factor. RESULTS: Compared with pathology, the efficacy of diagnosing LN metastasis only according to conventional endorectal ultrasonography (ERUS) features of LN was not high, with sensitivity 67%, specificity 86%, positive predictive value 76%, negative predictive value 80%, and accuracy 79%. Univariate analysis showed that circumferential angle of the tumor, ultrasonic T- stage (UT stage), conventional ultrasound features diagnosis of LN metastasis, strain ratio (SR) of tumor were risk factors for LN metastasis, while vascular resistance index of rectal tumor was protective factor. Multivariate analysis showed that UT stage (OR = 7.188, p = 0.049), conventional ultrasound features diagnosis of LN metastasis (OR = 8.010, p = 0.025) and SR (OR = 5.022, p = 0.031) were independent risk factors for LN metastasis. These risk factors were included in logistic regression analysis and the model was established, Y = -7.3 + 1.9 X10 + 2.1 X11 + 1.6 X13 (Y = Logit[P], P: LN metastasis rate, X10: UT stage, X11: conventional ultrasound features diagnosis of LN metastasis, X13: SR). The receiver operating characteristic (ROC) curve was used to test the model's predictive efficacy, the area under the curve was 0.95, sensitivity: 95%, specificity: 87%. Hosmer-Lemeshow goodness of fit test showed X2 = 6.015, p = 0.65 (p > 0.05), indicating that the model had a high predictive value. CONCLUSION: Evaluation of perirectal LN metastasis only based on conventional ERUS features of LN was not effective enough. UT stage of tumor, conventional ultrasound features diagnosis of LN metastasis and SR were independent risk factors for LN metastasis. The predictive model had good assessment efficacy and had certain clinical application value.

Comparing rice production systems in China: Economic output and carbon footprint.

In recent years, many rotational and integrated rice production systems coupled with several greenhouse gas (GHG) emissions mitigation practices have been developed and adopted for demand of low carbon production. However, there have been only few studies about comparisons on the balance between high production and mitigation of GHG emissions in different rice production systems. We therefore aimed to evaluate economic output and carbon footprint of different rice production systems, based on several long-term experiments conducted by our lab. CH4 and N2O emission were measured by the same static chamber/gas chromatogram measurement procedure in different rice production systems, including rice-fallow, rice-rapeseed, rice-wheat, double rice, and integrated rice-crayfish production system. Then, we applied the DeNitrification DeComposition model to simulate CH4 and N2O emission over different years under the same condition for comparison. Carbon footprint was calculated following the process-based life cycle assessment (PLCA) methodology. The economic benefit of rice production systems was assessed by cost-benefit analysis. According to the analysis, the double-rice production system exhibited the highest intensity of carbon footprint (ICF = 4.14 kg CO2-eq yuan-1), rain-fed treatment in the rice-rapeseed system had the lowest (ICF = 0.68 kg CO2-eq yuan-1). The intensity of carbon footprint in different treatments in the integrated rice-crayfish production system was around 0.8 kg CO2-eq yuan-1. Overall, the results of this case study suggest: (1) the proposed practices in different rice production systems are no straw returning (rice-fallow), no-tillage without straw returning (rice-wheat), rain-fed farming (rice-rapeseed), no insect and no inoculation (double rice), and feeding with straw returning (rice-crayfish); (2) rotational and integrated systems can achieve high net output with low carbon emission; (3) reducing the amount of nitrogenous fertilizer application is the most important and effective GHG mitigation practice for rotational systems.