Combining network pharmacology and experimental verification to reveal the mechanism of Chaigui granules in the treatment of depression through PI3K/Akt/mTOR signaling pathways.

INTRODUCTION: Chaigui granules are a novel manufactured traditional Chinese antidepressant medicine, which is originated from the ancient classical prescription of Xiaoyaosan. It ameliorated depression-like behavior and concomitant symptoms in animal models. But its antidepressant mechanism is still unclear. Therefore, network pharmacology and molecular biology were used to explore underlying antidepressant mechanism in this study. METHODS: Firstly, network pharmacology was used to screen main active ingredients and potential targets in the treatment of depression with Chaigui granules, and to perform pathway enrichment analysis. Secondly, chronic and unpredictable mild stress-induced depression model rats were used, and behavioral tests were used to evaluate the antidepressant effect of Chaigui granules. Finally, the core targets and key pathways predicted by network pharmacology were validated by qRT-PCR and Western blot to determine the relevant gene and protein expression levels in rat hippocampus. RESULTS: The results of network pharmacology indicated that the PI3K/Akt signaling pathway may play a key role in antidepressant of Chaigui granules. The results of animal experiments showed that Chaigui granules significantly modulated behavioral indicators. Subsequently, the upregulation of relative mRNA levels of mTOR, Akt and PI3K and downregulation of GSK-3ß and FoxO3a were observed in rat hippocampus by molecular biology diagnosis. In addition, the decreased expression of Akt and mTOR in CUMS rats hippocampus was significantly reversed, and the expression levels of GSK-3ß and FoxO3a were upregulated. CONCLUSIONS: Based on the results of network pharmacology and animal experiment validation, Chaigui granules may reverse CUMS-induced depression-like behavior in rats through PI3K/Akt/mTOR signaling pathway.

Revealing the role of leucine in improving the social avoidance behavior of depression through a combination of untargeted and targeted metabolomics.

Leucine is a common nutritional supplement, and recently, research concerned with the improvement role of leucine in neuropsychiatric disorders has been increasingly emphasized. However, it is unclear what role leucine plays in depression. In this study, the chronic social defeat stress (CSDS) model was used to simulate depression associated with social avoidance in humans. CSDS mice display a depressive state and social avoidance behavior. Untargeted serum metabolomics and pathway analysis indicated that abnormal amino acid metabolism may be the key to abnormal behavior in CSDS mice. Among these metabolites, leucine shows a specific and significant positive correlation with social interaction rate. Targeted metabolomics determine the decreased level of leucine and related metabolites in the serum and hippocampus of CSDS mice. Moreover, immunohistochemical results also indicate an increasing expression of IDO1 in hippocampal tissues in CSDS mice, and neurons may be damaged. Subsequently, leucine was administered to investigate its influence on CSDS mice, and the results revealed that leucine had a good effect on depressive states and social avoidance behaviors. Taken together, we aim to identify the important role of leucine as a functional food supplement to improve depression and social avoidance behavior through the above findings.

Graph-Based Motion Artifacts Detection Method from Head Computed Tomography Images.

Computed tomography (CT) images play an important role due to effectiveness and accessibility, however, motion artifacts may obscure or simulate pathology and dramatically degrade the diagnosis accuracy. In recent years, convolutional neural networks (CNNs) have achieved state-of-the-art performance in medical imaging due to the powerful learning ability with the help of the advanced hardware technology. Unfortunately, CNNs have significant overhead on memory usage and computational resources and are labeled 'black-box' by scholars for their complex underlying structures. To this end, an interpretable graph-based method has been proposed for motion artifacts detection from head CT images in this paper. From a topological perspective, the artifacts detection problem has been reformulated as a complex network classification problem based on the network topological characteristics of the corresponding complex networks. A motion artifacts detection method based on complex networks (MADM-CN) has been proposed. Firstly, the graph of each CT image is constructed based on the theory of complex networks. Secondly, slice-to-slice relationship has been explored by multiple graph construction. In addition, network topological characteristics are investigated locally and globally, consistent topological characteristics including average degree, average clustering coefficient have been utilized for classification. The experimental results have demonstrated that the proposed MADM-CN has achieved better performance over conventional machine learning and deep learning methods on a real CT dataset, reaching up to 98% of the accuracy and 97% of the sensitivity.

Design of a Blockchain-Enabled Traceability System Framework for Food Supply Chains.

Tracing food products along the entire supply chain is important for achieving better management of food products. Traditionally, centralized traceability systems have been developed for such purposes. One major drawback of this approach is that different users of the supply chain have their own systems with their own complexities and distinct features; thus, the interaction among them creates challenges when implementing a single centralized system. Therefore, a decentralized traceability system is favorable for tracing food products along the supply chain. In this study, we develop a supply chain traceability system framework based on blockchain and radio frequency identification (RFID) technology. The system consists of a decentralized blockchain-enabled data storage platform for data management and an RFID system at the packaging level for data collection and storage. We applied a consortium blockchain to the application. Fabric 2.0 in Hyperledger was chosen as the development platform. The proposed blockchain-enabled platform can provide decentralized data management and its underlying algorithm can guarantee data security. The system includes a creatively designed blockchain-enabled data structure in the RFID tag. When people scan the tag, the relevant information is written in the tag as a block linked to the previous blocks; simultaneously, the information is transmitted to the blockchain platform and recorded on the platform. No battery is required and the system works when there is an RFID reader nearby. The usage conditions included shipment, stocking, and storage. The RFID tag can be directly attached to paper packaging. This approach embeds the blockchain technique into the RFID tag and develops a corresponding system. The new traceability system has the potential to simplify the tracking of products and can be scaled for industrial use.

Research on Indoor 3D Positioning Algorithm Based on WiFi Fingerprint.

Indoor 3D positioning is useful in multistory buildings, such as shopping malls, libraries, and airports. This study focuses on indoor 3D positioning using wireless access points (AP) in an environment without adding additional hardware facilities in large-scale complex places. The integration of a deep learning algorithm into indoor 3D positioning is studied, and a 3D dynamic positioning model based on temporal fingerprints is proposed. In contrast to the traditional positioning models with a single input, the proposed method uses a sliding time window to build a temporal fingerprint chip as the input of the positioning model to provide abundant information for positioning. Temporal information can be used to distinguish locations with similar fingerprint vectors and to improve the accuracy and robustness of positioning. Moreover, deep learning has been applied for the automatic extraction of spatiotemporal features. A temporal convolutional network (TCN) feature extractor is proposed in this paper, which adopts a causal convolution mechanism, dilated convolution mechanism, and residual connection mechanism and is not limited by the size of the convolution kernel. It is capable of learning hidden information and spatiotemporal relationships from the input features and the extracted spatiotemporal features are connected with a deep neural network (DNN) regressor to fit the complex nonlinear mapping relationship between the features and position coordinates to estimate the 3D position coordinates of the target. Finally, an open-source public dataset was used to verify the performance of the localization algorithm. Experimental results demonstrated the effectiveness of the proposed positioning model and a comparison between the proposed model and existing models proved that the proposed model can provide more accurate three-dimensional position coordinates.

A Novel Rabbit Dry Eye Model Induced by a Controlled Drying System.

Purpose: To establish an environment-induced dry eye model in rabbits using a controlled drying system (CDS). Methods: Rabbits were randomly divided into two groups. The rabbits in the dry group were housed in the CDS, in which the relative humidity, airflow, and temperature were controlled at 22% ± 4%, 3 to 4 m/s, and 23°C to 25°C for 14 days. The rabbits in the control group were housed in a normal environment at the same time. A Schirmer test, fluorescein staining, and lissamine green staining were performed. On day 14, the eyeballs and lacrimal glands were processed for evaluating the corneal epithelial thickness, inflammatory cell infiltration index, goblet cell density, and expression of the MUC5AC protein and caspase-3 protein. The mRNA expression of the involved inflammatory genes was analyzed. Results: The CDS was able to maintain a dry environment, in which the tear production decreased, and the ocular surface staining increased over time in the rabbits. In the dry group, the corneal epithelium became thinner, inflammatory cells were noted, goblet cells and MUC5AC proteins decreased, and the increased levels of caspase-3 proteins and inflammatory cytokines were observed in the ocular surface tissues and lacrimal glands. Conclusions: This CDS could create a dry environment, in which the rabbits exhibited a pathological change in dry eye similar to that in humans. Translational Relevance: This model would be helpful in offering a platform to identify and test candidate therapies for environment-induced dry eye and to explore its underlying mechanisms.

Preparation of a novel bone wax with modified tricalcium silicate cement and BGs.

Amino-grafted and vaterite-contained tricalcium silicate cement (A-V-C3S) was composited with 58S bioglass/chitosan/carboxy methyl cellulose (BG/CS/CMC, referred as BGs) to surmount the non-absorbability and infection problems of traditional bone wax. Its material, bioactive, biocompatible and antibacterial properties were systematically characterized. The results revealed that A-V-C3S/BGs possessed self-setting, injectable, mechanical and degradable abilities. A-V-C3S/BGs (1:1 g/g) was optimum owing to its higher compressive strength (9.91 MPa) and lower pH value (7.6 to 8.1) in the test groups. In vitro immersion experiment demonstrated that A-V-C3S/BGs had good hydroxyapatite formation ability, and its excellent cell adhesion, low cytotoxicity and superior cell proliferation were verified by mouse embryonic osteoblast precursor cells in cell tests. Compared with A-V-C3S, antibacterial experiment illustrated the significantly enhanced antibacterial property of A-V-C3S/BGs to Staphylococcus aureus and Escherichia coli.

[Advancements in complex target systematic evolution of ligands by exponential enrichment].

Nucleic acid aptamers are single-stranded oligonucleotides that possess high affinity and specificity. They are also known as "chemical antibodies" and have a wide range of applications. Aptamers are usually generated by an in vitro process termed as systematic evolution of ligands by exponential enrichment (SELEX). Aptamers are often selected by employing purified soluble protein targets. However, the process of protein purification can be complex and laborious. Furthermore, several protein targets, such as low abundance proteins found in serums and membrane proteins found in cells, are difficult to purify. Complex target SELEX can avoid the purification step and maintain the native state of the target proteins. Even in the absence of detailed composition and characterization of a complex target, complex target SELEX can be performed with a high throughput for obtaining specific aptamers. In this study, complex target SELEX taken unpurified biological samples as targets will be described in order to provide a new idea for researchers screening aptamers.

Enhancing the biological activity of vaterite-containing ß-dicalcium silicate cement by silane coupling agent for biomaterials.

Vaterite-containing ß-dicalcium silicate powder (A-V-C2S) was successfully grafting modified by 3-aminopropyltriethoxysilane (APTES) through reflux agitation. The purpose of this work is to fix the amino groups on the vaterite-containing ß-dicalcium silicate (V-C2S) powder's surface, which makes the powder's surface with positive charge, and further enhanced the combination with those negatively charged bioactive molecules or drugs to improve the performance of biomaterials. XRD and FT-IR analysis indicated that N-H groups were successfully grafted onto the surface of the V-C2S sample on the basis of vaterite existence through the process of first grafting then carbonation. Moreover, the best grafting modification that refluxing at 70 °C for 12 h was determined through the quantitative analysis of N-H groups on V-C2S powder's surface. The A-V-C2S sample showed a better apatite formation ability after it was soaked in stimulated body fluid (SBF), indicating that good apatite mineralization. Moreover, the A-V-C2S sample with weak alkali in implanting position could stimulate the attachment, proliferation and improve the activity of MC3T3-E1 cells. Experimental results demonstrated that, A-V-C2S was expected to be a new biomaterial as bone repairing substitute.

Novel bone wax based on tricalcium silicate cement and BGs mixtures.

Classic bone wax is effectively hemostatic and low-cost, but it has shortcomings like infection and nonabsorbability. A novel self-curing bone wax was developed by mixing tricalcium silicate (C3S) cement and 58S bioactive glass/chitosan/carboxy methyl cellulose (BG/CS/CMC, referred to as BGs) to overcome these problems. It was found that the addition of BGs improved anti-washout and operational properties of C3S, and C3S had good self-curing and mechanical behavior. C3S/BGs with a mass ratio of 2:1 possessed better material performance in the setting time, mechanical strength, and injection property in the test group. X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, and scanning electron microscopy (SEM) confirmed the hydroxyapatite (HAp) formation ability of C3S/BGs. The cell compatibility was investigated in vitro by culturing mouse embryonic osteoblast precursor cells (MC3T3-E1) in the extract of C3S/BGs. The results showed that the bone wax compound presented low cytotoxicity and good cell proliferation.

Novel vaterite-containing tricalcium silicate bone cement by surface functionalization using 3-aminopropyltriethoxysilane: setting behavior, in vitro bioactivity and cytocompatibility.

A novel vaterite-containing tricalcium silicate (V-C3S) was grafted by 3-aminopropyltriethoxysilane (APTES), and the amino groups have been successfully fixed on the vaterite-containing tricalcium silicate powder's surface (after grafting the amino group, V-C3S was named A-V-C3S). The setting behavior, mechanical properties, porosity, weight loss and anti-washout properties of the tricalcium silicate (C3S), V-C3S and A-V-C3S bone cement were systematically investigated. The in vitro induction of hydroxyapatite (HAp) formation of C3S, V-C3S and A-V-C3S bone cement was confirmed by x-ray diffraction, Fourier-transform infrared spectroscopy and scanning electron microscopy. The cell viability, cell proliferation and cell attachment were investigated to assess the effects of bone cement on MC3T3-E1 cells. Results showed that the setting time of A-V-C3S bone cement can meet the requirements of a clinical test, with improved anti-washout properties and an appropriate degradation rate. The pH value of the soaking solution was obviously decreased by surface modification. Besides, the morphology and fluorescence photograph results revealed that the A-V-C3S bone cement showed an enhanced biocompatibility effect on the proliferation and attachment of MC3T3-E1 cells. The A-V-C3S bone cement was expected to be a potential bone-substitute material.

A novel bioactive vaterite-containing tricalcium silicate bone cement by self hydration synthesis and its biological properties.

A novel bioactive vaterite-containing tricalcium silicate bone cement (V5) was successfully synthesized through self hydration and carbonization, by introducing CO2 into the hydration process of Ca3SiO5 (C3S). The purpose of this work is to reduce the adverse effect of the hydration products Ca(OH)2 on the C3S bone cement, and improve further the bioactivity of the C3S bone cement. XRD and FT-IR analysis indicated that vaterite was successfully formed in tricalcium silicate bone cement. The in vitro bioactivity of V5 was investigated by soaking in simulated body fluid (SBF) for various periods (1, 3, 7days), in addition to setting time, compressive strength and cell behavior. The results showed that the V5 could rapidly induce hydroxyapatite (HA) formation. The bio-effects of V5 on MC3T3-E1 osteoblast-like cells were evaluated by studying cell viability, adhesion and proliferation. The CCK-8 assay shows that cell viability on the resulting V5 is improved obviously after through hydration and carbonization. The V5 cement enhanced the higher expression of cell attachment, proliferation and differentiation as compared to V50 cement. SEM results present significant improvement on the cell adhesion and proliferation for cells cultured on the V5. Experimental results demonstrated that, C3S bone cement of containing vaterite has more excellent bioactivity and medium setting time too, suggesting their potential applications in areas such as MC3T3-E1 cell stimulation and bone tissue engineering.

Amino-functionalized mesoporous bioactive glass for drug delivery.

An amino-functionalized mesoporous bioactive glass (N-MBG) with a high drug loading capacity and longer drug release time was successfully prepared by using 3-aminopropyltriethoxysilane (APTES) in a short-time chemical reaction. The drug release performance of an MBG and the N-MBG were studied by loading gentamicin sulfate (GS) in a simulated body fluid solution. The results showed that the surface area of the N-MBG increases to 355.01 m2 g-1 after amination at 80 °C for 1 h compared with that of the MBG (288.07 m2 g-1). Meanwhile, the surface zeta-potential of the N-MBG charges from the original negative charge (-10.06 mV) to the positive charge (+5.30 mV). Furthermore, the GS loading rate of the N-MBG is up to 62.92 ± 2.02%, higher than that of the MBG (48.90 ± 1.71%). In addition, the N-MBG has a longer drug release period and the seven-day accumulative release from the N-MBG reached only 45.9 ± 1.8%, significantly lower than that of the MBG, 60.7 ± 2.3%. In vitro bioactivity tests suggested that the N-MBG exhibited good biological activity. In conclusion, the N-MBG with a higher loading capacity and longer drug release time can serve as a promising candidate as a drug carrier.