Aerobic exercise improves cognitive impairment in mice with type 2 diabetes by regulating the MALAT1/miR-382-3p/BDNF signaling pathway in serum-exosomes

Abstract Background It has been documented that aerobic exercise (AE) has a positive effect on improving cognitive function in type 2 diabetes (T2DM) patients. Here, we tried to explore how AE regulates the expression of long non-coding RNA in serum-exosomes (Exos), thereby affecting cognitive impairment in T2DM mice as well as its potential molecular mechanism. Methods T2DM mouse models were constructed, and serum-Exos were isolated for whole transcriptome sequencing to screen differentially expressed lncRNA and mRNA, followed by prediction of downstream target genes. The binding ability of miR-382-3p with a long non-coding RNA MALAT1 and brain-derived neurotrophic factor (BDNF) was explored. Then, primary mouse hippocampal neurons were collected for in vitro mechanism verification, as evidenced by the detection of hippocampal neurons' vitality, proliferation, and apoptosis capabilities, and insulin resistance. Finally, in vivo mechanism verification was performed to assess the effect of AE on insulin resistance and cognitive disorder. Results Transcriptome sequencing analysis showed that MALAT1 was lowly expressed and miR-382-3p was highly expressed in serum-Exos samples of T2DM mice. There were targeted binding sites between MALAT1 and miR-382-3p and between miR-382-3p and BDNF. In vitro experiments showed that MALAT1 upregulated BDNF expression by inhibiting miR-382-3p. Silencing MALAT1 or overexpressing miR-382-3p could reduce the expression of INSR, IRS-1, IRS-2, PI3K/AKT, and Ras/MAPK, inhibit neuronal proliferation, and promote apoptosis. In vivo experiments further confirmed that AE could increase the expression of MALAT1 in serum-Exos to competitively inhibit miR-382-3p and upregulate BDNF expression, thereby improving cognitive impairment in T2DM mice. Conclusion AE may upregulate the expression of MALAT1 in serum-Exos to competitively inhibit miR-382-3p and upregulate BDNF expression, thus improving cognitive impairment in T2DM mice

Faba Bean (<i>Vicia faba</i> L.) Yield Estimation Based on Dual-Sensor Data

Faba bean is an important member of legumes, which has richer protein levels and great development potential. Yield is an important phenotype character of crops, and early yield estimation can provide a reference for field inputs. To facilitate rapid and accurate estimation of the faba bean yield, the dual-sensor (RGB and multi-spectral) data based on unmanned aerial vehicle (UAV) was collected and analyzed. For this, support vector machine (SVM), ridge regression (RR), partial least squares regression (PLS), and k-nearest neighbor (KNN) were used for yield estimation. Additionally, the fusing data from different growth periods based on UAV was first used for estimating faba bean yield to obtain better estimation accuracy. The results obtained are as follows: for a single-growth period, S2 (12 July 2019) had the best accuracy of the estimation model. For fusion data from the muti-growth period, S2 + S3 (12 August 2019) obtained the best estimation results. Furthermore, the coefficient of determination (R2) values for RF were higher than other machine learning algorithms, followed by PLS, and the estimation effects of fusion data from a dual-sensor were evidently better than from a single sensor. In a word, these results indicated that it was feasible to estimate the faba bean yield with high accuracy through data fusion based on dual-sensor data and different growth periods

Additional file 3 of Aerobic exercise improves cognitive impairment in mice with type 2 diabetes by regulating the MALAT1/miR-382-3p/BDNF signaling pathway in serum-exosomes

Additional file 3: Table S1. In vivo experimental grouping and treatments. Table S2. shRNA sequences. Table S3. In vitro cell experimental grouping and treatments. Table S4. The primer sequence of RT-qPCR. Table S5. Primary antibody product information. Table S6. T2DM-related lncRNAs obtained from the MNDR database

Additional file 1 of Aerobic exercise improves cognitive impairment in mice with type 2 diabetes by regulating the MALAT1/miR-382-3p/BDNF signaling pathway in serum-exosomes

Additional file 1: Fig. S1. Experimental verification of whether serum Exos can pass through the blood–brain barrier. Note: (A) Observation of neuron uptake of Exos by confocal fluorescence microscopy (400 ×); (B) RT-qPCR detection of MALAT1 and miR-382-3p expression in hippocampal neurons (P < 0.05 compared with the control + PBS group); C–E: RT-qPCR detection of MALAT1 and miR-382-3p expression in CPE, CSF, and brain parenchyma; (F) Observation of brain and hippocampal uptake of Exos by confocal fluorescence microscopy (20 × , 100 ×); (G) RT-qPCR detection of MALAT1 and miR-382-3p expression in mouse brain hippocampal tissue; n = 10, *, P < 0.05 compared with the PBS group, #, P < 0.05 compared with the Exos + DMSO group; all cell experiments were repeated three times

Additional file 2 of Aerobic exercise improves cognitive impairment in mice with type 2 diabetes by regulating the MALAT1/miR-382-3p/BDNF signaling pathway in serum-exosomes

Additional file 2: Fig. S2. Schematic diagram illustrating the molecular mechanism of aerobic exercise improving cognitive impairment in T2DM mice by regulating the MALAT1/miR-382-3p/BDNF signaling pathway in serum-exosomes