Simvastatin Blocks Blood-Brain Barrier Disruptions Induced by Elevated Cholesterol Both In Vivo and In Vitro

Background. Hypercholesterolemia and disruptions of the blood brain barrier (BBB) have been implicated as underlying mechanisms in the pathogenesis of Alzheimer's disease (AD). Simvastatin therapy may be of benefit in treating AD; however, its mechanism has not been yet fully understood. Objective. To explore whether simvastatin could block disruption of BBB induced by cholesterol both in vivo and in vitro. Methods. New Zealand rabbits were fed cholesterol-enriched diet with or without simvastatin. Total cholesterol of serum and brain was measured. BBB dysfunction was evaluated. To further test the results in vivo, rat brain microvascular endothelial cells (RBMECs) were stimulated with cholesterol in the presence/absence of simvastatin in vitro. BBB disruption was evaluated. Results. Simvastatin blocked cholesterol-rich diet induced leakage of Evan's blue dye. Cholesterol content in the serum was affected by simvastatin, but not brain cholesterol. Simvastatin blocked high-cholesterol medium-induced decrease in TEER and increase in transendothelial FITC-labeled BSA Passage in RBMECs. Conclusions. The present study firstly shows that simvastatin improves disturbed BBB function both in vivo and in vitro. Our data provide that simvastatin may be useful for attenuating disturbed BBB mediated by hypercholesterolemia

Identification of a novel peptide targeting TIGIT to evaluate immunomodulation of 125I seed brachytherapy in HCC by near-infrared fluorescence

IntroductionHepatocellular carcinoma (HCC) has very poor prognosis due to its immunosuppressive properties. An effective measure to regulate tumor immunity is brachytherapy, which uses 125I seeds planted into tumor. T cell immune receptors with immunoglobulin and ITIM domains (TIGIT) is highly expressed in HCC. The TIGIT-targeted probe is expected to be an effective tool for indicating immunomodulation of 125I seed brachytherapy in HCC. In this study, We constructed a novel peptide targeting TIGIT to evaluate the immune regulation of 125I seed brachytherapy for HCC by near-infrared fluorescence (NIRF).MethodsExpression of TIGIT by immunofluorescence (IF) and flow cytometry (FCM) in different part and different differentiated human liver cancer tissues was verified. An optical fluorescence probe (Po-12) containing a NIRF dye and TIGIT peptide was synthesized for evaluating the modulatory effect of 125I seed brachytherapy. Lymphocytes uptake by Po-12 were detected by FCM and confocal microscopy. The distribution and accumulation of Po-12 in vivo were explored by NIRF imaging in subcutaneous and orthotopic tumors. IHC and IF staining were used to verify the expression of TIGIT in the tumors.ResultsTIGIT was highly expressed in HCC and increased with tumor differentiation. The dye-labeled peptide (Po-12) retained a stable binding affinity for the TIGIT protein in vitro. Accumulation of fluorescence intensity (FI) increased with time extended in subcutaneous H22 tumors, and the optimal point is 1 h. TIGIT was highly expressed on lymphocytes infiltrated in tumors and could be suppressed by 125I seed brachytherapy. Accumulation of Po-12-Cy5 was increased in tumor-bearing groups while declined in 125I radiation group

BASP1 is a prognostic biomarker associated with immunotherapeutic response in head and neck squamous cell carcinoma

BackgroundsImmunotherapy is effective in a subset of head and neck squamous cell carcinoma (HNSCC). However, the unfavorable response rate and inadequate biomarkers for stratifying patients have primarily limited its clinical application. Considering transcriptional factors (TFs) play essential roles in regulating immune activity during HNSCC progression, we comprehensively analyzed the expression alterations of TFs and their prognostic values.MethodsGene expression datasets and clinical information of HNSCC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) repository. Then, Brain abundant membrane attached signal protein 1 (BASP1) was screened out of differentially expressed TFs by univariate and multivariate survival analysis. Tumor immune dysfunction and exclusion (TIDE) was applied to analyze the response to immunotherapy of BASP1high/low patients. Meanwhile, GO, KEGG and GSEA analyses were used to enrich the pathways between the BASP1high and BASP1low groups. Single-sample gene set enrichment analysis (ssGSEA), CIBERSORT, EPIC and quanTiseq algorithms were applied to explore immune infiltrations. Also, immune cycle analysis was conducted by ssGSEA. Additionally, lipid peroxidation, glutathione and reactive oxygen species were performed to detect the ferroptosis alternations.ResultsBASP1 was upregulated and associated with poor survival in HNSCC patients. BASP1high patients exhibited better response rates to anti-PD-1 immunotherapy and higher expressions of immune checkpoint inhibitors. GO, KEGG and GSEA analyses indicated that the expression of BASP1 was related to several immune-related pathways and immunogenic ferroptosis signature. The infiltration of activated CD8+ T cells was authenticated to be decreased in BASP1high patients. Furthermore, BASP1 was identified to be positively correlated with T cell dysfunction and immune escape. Moreover, silencing BASP1 triggered ferroptosis in HNSCC cells, representing as increased LDH, lipid peroxidation and ROS levels, and reduced glutathione synthesisConclusionsWe demonstrated that BASP1 suppressed immunogenic ferroptosis to induce immunosuppressive tumor microenvironment. BASP1 plays a critical role in immune response, and might be a promising classifier for selecting HNSCC patients who benefit from current immunotherapy

Application of metal-organic frameworks, covalent organic frameworks and their derivates for the metal-air batteries

Metal-organic frameworks (MOFs) and covalent organic frameworks (COFs) as the novel porous materials have the merits of diverse, adjustable functionality, high porosity and surface area, which have great application prospects in the gas storage, separation and catalysis. In addition, their derivates make up for the insufficient of electronic conductivity and chemical stability of MOFs and COFs, and provide a new ideal for accurate control of material structure. Up to now, many efficient electrocatalysts have been designed based on MOFs, COFs and their derivates for O2 reduction/evolution reactions (ORR/OER) and CO2 reduction/evolution reactions (CO2RR/CO2ER) in the metal-air batteries. In this review, the latest development of MOFs, COFs and their derivates in the metal-air batteries is summarized, and we discuss the structural characteristics of these materials and their corresponding mechanisms of action. By comprehensively reviewing the advantages, challenges and prospects of MOFs and COFs, we hope that the organic framework materials will shed more profound insights into the development of electrocatalysis and energy storage in the future

Intelligent Home Monitoring System Based on Internet of Things

To realize the remote monitoring and intelligent management of the home environment, intelligent home remote monitoring system is developed based on the Internet of things technology. By using RF transceiver chip and GPRS technology, a smart home system scheme for wireless networks is established. The hardware and software design of sensor nodes and GPRS wireless communication base station is completed. Sensor nodes are used to monitor the acquisition of field data. Based on GPRS technology, the wireless communication base station realizes the uploading of monitoring data. The wireless communication between the node and the base station is realized by radio frequency transceiver chip SI4432. The results show that the system reaches the aim of expected design function. Therefore, it can be concluded that the system can meet the intelligent monitoring of the home environment

A Human Body Gait Recognition System Based on Fourier Transform and Quartile Difference Extraction

A research method of gait recognition based on feature combination is proposed, which includes the wavelet transform (WT), Fourier transform (FT) and the quartile difference, to explore the gait recognition system in Internet of things human body sensor based on smart phone. It can extract the low-dimensional gait parameters of the acceleration signal, and these gait parameters can reflect the movement characteristics. Then, they are combined into feature vector to identify by a pattern recognition algorithm.Finally, the experimental verification is carried out in the experimental system. The results show thatthis gait recognition method simplifies the processing flow to a certain extent, and improves the recognition accuracy. In conclusion, the algorithm has a good effect, and can identify the gait behavior with high precision

Learning Coupled Oscillators System with Reservoir Computing

In this paper, we reconstruct the dynamic behavior of the ring-coupled Lorenz oscillators system by reservoir computing. Although the reconstruction of various complex chaotic attractors has been well studied by using various neural networks, little attention has been paid to whether the spatio-temporal structure of some special attractors can be maintained in long-term prediction. Reservoir computing has been shown to be effective for model-free prediction, so we want to investigate whether reservoir computing can restore the rotational symmetry of the original ring-coupled Lorenz system. We find that although the state prediction of the trained reservoir computer will gradually deviate from the actual trajectory of the original system, the associated spatio-temporal structure is maintained in the process of reconstruction. Specifically, we show that the rotational symmetric structure of periodic rotating waves, quasi-periodic torus, and chaotic rotating waves is well maintained

Learning Coupled Oscillators System with Reservoir Computing

In this paper, we reconstruct the dynamic behavior of the ring-coupled Lorenz oscillators system by reservoir computing. Although the reconstruction of various complex chaotic attractors has been well studied by using various neural networks, little attention has been paid to whether the spatio-temporal structure of some special attractors can be maintained in long-term prediction. Reservoir computing has been shown to be effective for model-free prediction, so we want to investigate whether reservoir computing can restore the rotational symmetry of the original ring-coupled Lorenz system. We find that although the state prediction of the trained reservoir computer will gradually deviate from the actual trajectory of the original system, the associated spatio-temporal structure is maintained in the process of reconstruction. Specifically, we show that the rotational symmetric structure of periodic rotating waves, quasi-periodic torus, and chaotic rotating waves is well maintained