Background: Impaired mitophagy results in the accumulation of defective mitochondria that are unable to be cleared effectively in Alzheimer's disease (AD). Aloe‐emodin (AE), a key component of the traditional Chinese medicine Rhubarb, exhibits neuroprotective effects against Alzheimer's disease, though the underlying mechanism remains unclear. Studying aloe‐emodin's role in enhancing mitophagy is vital for improving cognitive function and reducing neuronal damage in Alzheimer's disease.Methods: The APP/PS1 double transgenic mice were adopted as models for AD to assess the effects of aloe‐emodin upon cognitive function and its neuroprotective impact on hippocampal neurons. Additionally, we investigated the regulatory mechanisms of proteins within the aforementioned pathway, and the morphological characteristics of mitophagy‐related proteins. An AD hippocampal neuron model was developed using Aβ25‐35 to evaluate the mitochondrial function, the protein expression of such a pathway and the mitophagy. This approach aims to elucidate the effects and underlying mechanisms of aloe‐emodin in relation to AD.Results: AE activates mitophagy in neurons, improves cognitive dysfunction, reduces hippocampal damage, and alleviates AD symptoms in model mice. AE activates the expression of AMPK, PGC‐1α and SIRT3. Increased expression of SIRT3 in mitochondria promotes mitophagy and regulates the function of mitochondrial proteins. When mitochondrial autophagy is enhanced, the expression of Beclin1, LC3, P62, Parkin, and PINK1‐related proteins changes. Further in vitro experiments showed that AE can enhance mitochondrial function in Alzheimer's disease cell models. The mitochondrial membrane potential, GSH, ROS and Ca2+ levels gradually recover, alleviating the pathological manifestations of AD. Knocking down SIRT3 leads to increased mitochondrial damage and a reduction in mitophagy in HT22 cells.Conclusion: Experimental results show that AE can activate mitophagy through AMPK/PGC‐1α/SIRT3 pathway, alleviate cognitive dysfunction in AD, and reduce damage to hippocampal neurons.

Melatonin has been indicated to ameliorate tau hyperphosphorylation in the pathogenesis of tau diseases, but the role of melatonin-receptor signal transduction has not been clearly discovered. In this study, we found intensive tau hyperphosphorylation in melatonin receptor knockout mice. Bielschowsky silver staining showed ghostlike neurofibrillary tangles in melatonin receptor-2 knockout (MT2KO) as well as melatonin receptors-1 and -2 knockout (DKO) mice, and an argyrophilic substance was deposited in melatonin receptor-1 knockout (MT1KO) mice. Furthermore, we found significantly decreased activity of protein phosphatase 2A (PP2A) by Western blot and enzyme-linked immunosorbent assay (ELISA), which was partly due to the overexpression of protein phosphatase methylesterase-1 (PME-1), but not glycogen synthase kinase-3β (GSK-3β), cyclin-dependent kinase 5 (CDK5) or protein kinase B (Akt). Finally, we observed a significant increase in cyclic adenosine monophosphate (cAMP) and a decrease in miR-125b-5p levels in MT1KO, MT2KO and DKO mice. Using a luciferase reporter assay, we discovered that miR-125b-5p largely decreased the expression of firefly luciferase by interfering with the 3′UTR of PME-1. Furthermore, miR-125b-5p mimics significantly decreased the expression of PME-1, while miR-125b-5p inhibitor induced tau hyperphosphorylation. These results show that melatonin-receptor signal transduction plays an important role in tau hyperphosphorylation and tangle formation.

The fisheye camera has a field of view (FOV) of over 180°, which has advantages in the fields of medicine and precision measurement. Ordinary pinhole models have difficulty in fitting the severe barrel distortion of the fisheye camera. Therefore, it is necessary to apply a nonlinear geometric model to model this distortion in measurement applications, while the process is computationally complex. To solve the problem, this paper proposes a model-free stereo calibration method for binocular fisheye camera based on neural-network. The neural-network can implicitly describe the nonlinear mapping relationship between image and spatial coordinates in the scene. We use a feature extraction method based on three-step phase-shift method. Compared with the conventional stereo calibration of fisheye cameras, our method does not require image correction and matching. The spatial coordinates of the points in the common field of view of binocular fisheye camera can all be calculated by the generalized fitting capability of the neural-network. Our method preserves the advantage of the broad field of view of the fisheye camera. The experimental results show that our method is more suitable for fisheye cameras with significant distortion.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumor. miR-331-3p has been reported relevant to the progression of HCC, but the molecular mechanism of its regulation is still unclear. In the study, we comprehensively studied the role of miR-331-3p in HCC through weighted gene coexpression network analysis (WGCNA) based on The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Oncomine. WGCNA was applied to build gene co-expression networks to examine the correlation between gene sets and clinical characteristics, and to identify potential biomarkers. Five hundred one target genes of miR-331-3p were obtained by overlapping differentially expressed genes (DEGs) from the TCGA database and target genes predicted by miRWalk. The critical turquoise module and its eight key genes were screened by WGCNA. Enrichment analysis was implemented based on the genes in the turquoise module. Moreover, 48 genes with a high degree of connectivity were obtained by protein–protein interaction (PPI) analysis of the genes in the turquoise module. From overlapping genes analyzed by WGCNA and PPI, two hub genes were obtained, namely coatomer protein complex subunit zeta 1 (COPZ1) and elongation factor Tu GTP binding domain containing 2 (EFTUD2). In addition, the expression of both hub genes was also significantly higher in tumor tissues compared with normal tissues, as confirmed by analysis based on TCGA and Oncomine. Both hub genes were correlated with poor prognosis based on TCGA data. Receiver operating characteristic (ROC) curve validated that both hub genes exhibited excellent diagnostic efficiency for normal and tumor tissues.