Design and application of secondary operation and maintenance supervision system based on AR modeling and indoor positioning.

In order to facilitate the observation in the process of secondary equipment operation and maintenance supervision and the detection and tracking of operation and maintenance personnel, a secondary operation and maintenance supervision system based on AR modeling and indoor positioning is designed. The whole system is divided into seven levels and a unified information base, in which the basic level contains all kinds of secondary equipment; AR modeling layer uses augmented reality technology to create models for each secondary equipment in the basic layer, and determines the equipment position information based on ranging positioning technology; The data acquisition layer collects all kinds of original management data based on the constructed secondary equipment model; The data analysis layer reads and analyzes the information of the data acquisition layer through the data bus; The process support layer provides task scheduling support for the integrated management application based on the data analysis results; The integrated application layer uniformly monitors the secondary equipment based on the task scheduling results; The presentation layer is responsible for the interface presentation of all operation and maintenance and security management information of the system, and the unified information base provides data support for the whole system. The experimental results show that the secondary equipment model in the designed system has high definition, can obtain more image details, can realize the 3D display and real-time interaction of the secondary equipment operation and maintenance supervision results, and accurately mark the target and track for the staff.

Ginsenoside Rg1 improves Alzheimer's disease by regulating oxidative stress, apoptosis, and neuroinflammation through Wnt/GSK-3ß/ß-catenin signaling pathway.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder that can cause cognitive impairment. Ginsenoside Rg1 (Rg1) has a significant neuroprotective effect on animals with memory impairment. However, the mechanism of how Rg1 mediates the Wnt signaling pathway and improves cognitive function by regulating oxidative stress, apoptosis, and neuroinflammation is still unclear. In this study, the spatial memory ability of tree shrews was tested by Morris water maze, the expression levels of amyloid protein (Aß1-42), ionized calcium-binding adapter molecule 1 (iba-1), nitrotyrosine (NT), and 8-hydroxyguanine (8-OHG) were detected by immunohistochemistry. Subsequently, the activity of catalase (CAT) and the glutathione peroxidase (GSH-Px) was, respectively, measured by the ammonium molybdate method and the 5,5'-dithiobis (2-nitrobenzoic acid). Furthermore, the malondialdehyde (MDA) concentration was determined by the thiobarbituric acid test. Finally, the expression levels of Beta-secretase (BACE1), superoxide dismutase (SOD), BCL2-Associated X (Bax), B-cell lymphoma-2 (Bcl-2), caspase-anti-apoptotic factor Cleaved-caspase-3 (Caspase-3), microtubule-associated proteins 2 (MAP2), Neuronal nuclear antigen (NeuN), as well as the phosphorylation of GSK-3ß and ß-catenin were detected by Western blot. This study implied that Rg1 reduced the phosphorylation of Tau protein, the deposition of Aß1-42, and the expression of BACE1. It also showed that Rg1 increased the antioxidant activity of SOD, CAT, GPx, and instead reduced the oxidation products of NT, 8-OHG, and MDA, as wells as the inflammatory factor interleukin-1 and iba-1. It further showed that Rg1 increased the ratio of Bcl-2 to Bax and expression of neuronal markers MAP2 and NeuN, but instead reduced the expression of Caspase-3, GSK-3ß, and ß-catenin. In conclusion, by regulating the Wnt/GSK-3ß/ß-catenin signaling pathway, Rg1 of moderate and high dose could alleviate oxidative stress damage, improve neuroinflammation, protect neurons, finally improve the cognitive impairment of the AD tree shrew. This study provides theoretical basis for the Rg1 clinical application in AD.

Gastrodin induces lysosomal biogenesis and autophagy to prevent the formation of foam cells via AMPK-FoxO1-TFEB signalling axis.

Abnormal accumulation of lipids and massive deposition of foam cells is a primary event in the pathogenesis of atherosclerosis. Recent studies have demonstrated that autophagy and lysosomal function of atherosclerotic macrophages are impaired, which exacerbates the accumulation of lipid in macrophages and formation of foam cells. Gastrodin, a major active component of Gastrodia elata Bl., has exerted a protective effect on nervous system, but the effect of gastrodin on atherosclerotic vascular disease remains unknown. We aimed to evaluate the effect of gastrodin on autophagy and lysosomal function of foam cells and explored the mechanism underlying gastrodin's effect on the formation of foam cells. In an in vitro foam cell model constructed by incubating macrophages with oxygenized low-density lipoproteins (ox-LDL), our results showed that lysosomal function and autophagy of foam cells were compromised. Gastrodin restored lysosomal function and autophagic activity via the induction of lysosomal biogenesis and autophagy. The restoration of lysosomal function and autophagic activity enhanced cholesterol efflux from macrophages, therefore, reducing lipid accumulation and preventing formation of foam cells. AMP-activated protein kinase (AMPK) was activated by gastrodin to promote phosphorylation and nuclear translocation of forkhead box O1 (FoxO1), subsequently resulting in increased transcription factor EB (TFEB) expression. TFEB was activated by gastrodin to promote lysosomal biogenesis and autophagy. Our study revealed that the effect of gastrodin on foam cell formation and that induction of lysosomal biogenesis and autophagy of foam cells through AMPK-FoxO1-TFEB signalling axis may be a novel therapeutic target of atherosclerosis.

Ginsenoside Rg1 improves cognitive capability and affects the microbiota of large intestine of tree shrew model for Alzheimer's disease.

Ginsenoside Rg1 (Rg1) is traditional Chinese medicine with neuroprotective activity. Previous studies have demonstrated that Rg1 improves Alzheimer's disease (AD) and alters gut microbiology, but its mechanism remains to be elucidated, and thus far, its use in the treatment of AD has not been satisfactory. The present study investigated the improvement effects of Rg1 and its association with the microbiota of the large intestine. Following treatment with Rg1 in AD tree shrews, the treatment group demonstrated significantly shorter escape latency and crossed a platform more frequently in a water maze test. Western blotting demonstrated that Rg1 inhibited the expression of ß-secretase 1, while increasing microtubule-associated protein 2 and Fox-3 in the hippocampus. Immunohistochemical analysis revealed that Rg1 decreased the expression of amyloid ß, tau phosphorylated at serine 404 and pro-apoptotic factor Bax, while increasing the expression of Bcl-2 in the hippocampus and cortex. High throughput sequencing of 16S rRNA demonstrated that Rg1 altered the microbiota abundance of the large intestine. In conclusion, Rg1 affected the expression of apoptosis proteins, possessed a neuroprotective effect and may have a close association with the microbiota of large intestine by significantly reducing the abundance of Bacteroidetes and increasing the energy requirement of tree shrews.

A chitosan-based cascade-responsive drug delivery system for triple-negative breast cancer therapy.

BACKGROUND: It is extremely difficult to develop targeted treatments for triple-negative breast (TNB) cancer, because these cells do not express any of the key biomarkers usually exploited for this goal. RESULTS: In this work, we develop a solution in the form of a cascade responsive nanoplatform based on thermo-sensitive poly(N-vinylcaprolactam) (PNVCL)-chitosan (CS) nanoparticles (NPs). These are further modified with the cell penetrating peptide (CPP) and loaded with the chemotherapeutic drug doxorubicin (DOX). The base copolymer was optimized to undergo a phase change at the elevated temperatures of the tumor microenvironment. The acid-responsive properties of CS provide a second trigger for drug release, and the inclusion of CPP should ensure the formulations accumulate in cancerous tissue. The resultant CPP-CS-co-PNVCL NPs could self-assemble in aqueous media into spherical NPs of size < 200 nm and with low polydispersity. They are able to accommodate a high DOX loading (14.8% w/w). The NPs are found to be selectively taken up by cancerous cells both in vitro and in vivo, and result in less off-target cytotoxicity than treatment with DOX alone. In vivo experiments employing a TNB xenograft mouse model demonstrated a significant reduction in tumor volume and prolonging of life span, with no obvious systemic toxicity. CONCLUSIONS: The system developed in this work has the potential to provide new therapies for hard-to-treat cancers.

PTEN/PIK3CA genes are frequently mutated in spontaneous and medroxyprogesterone acetate-accelerated 7,12-dimethylbenz(a)anthracene-induced mammary tumours of tree shrews.

Tree shrew has increasingly become an attractive experimental animal model for human diseases, particularly for breast cancer due to spontaneous breast tumours and their close relationship to primates and by extension to humans. However, neither normal mammary glands nor breast tumours have been well characterised in the Chinese tree shrew (Tupaia belangeri chinensis). In this study, normal mammary glands from four different developmental stages and 18 spontaneous breast tumours were analysed. Haematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) showed that normal mammary gland morphology and structures of tree shrews were quite similar to those found in humans. Spontaneous breast tumours of tree shrews were identified as being intraductal papilloma, papillary carcinoma, and invasive ductal carcinoma with or without lung metastasis. To further analyse breast cancer tumours among tree shrews, 40 3-4 month-old female tree shrews were orally administrated 20 mg 7,12-dimethylbenz(a)anthracene (DMBA) or peanut oil thrice, and then, 15 of these DMBA administrated tree shrews were implanted with medroxyprogesterone acetate (MPA) pellets. DMBA was shown to induce breast tumours (12%) while the addition of MPA increased the tumour incidence (50%). Of these, three induced breast tumours were intraductal papillary carcinomas and one was invasive ductal carcinoma (IDC). The PTEN/PIK3CA (phosphatase and tensin homologue/phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), but not TP53 and GATA3, genes are frequently mutated in breast tumours, and the PTEN/PIK3CA gene mutation status correlated with the expression of pAKT in tree shrew breast tumours. These results suggest that tree shrews may be a promising animal model for a subset of human breast cancers with PTEN/PIK3CA gene mutations.

Characterization of spontaneous breast tumor in tree shrews (Tupaia belangeri chinenesis).

Breast cancer is a common malignant tumor. It is essential to develop suitable animal models for discovering novel preventive and therapeutic approaches. Tree shrews (Tupaia belangeri chinensis) have a closer evolutionary relationship with humans than do rodents, which have been widely used in laboratory research. Spontaneous breast tumors were identified in tree shrews in 1960s; however, no detailed studies about tree shrew breast tumors have been conducted to date. Here, we characterized a spontaneous breast tumor from tree shrews by Haematoxylin Eosin (H&E) staining. This tumor was identified as a papillary tumor. Immunohistochemical staining (IHC) for progesterone receptor (PR), Ki-67 and cleaved caspase-3 showed that tumor cells were positive for PR, highly proliferative, and less apoptotic compared to normal breast epithelial cells. Thus, the spontaneous tumor of tree shrew is very close to human papillary tumors in terms of morphology and pathology and we concluded that tree shrew may be a suitable animal model for breast cancer research.