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IntroductionAdvances in mobile computing platforms and the rapid development of wearable devices have made possible the continuous monitoring of patients with mild cognitive impairment (MCI) and their daily activities. Such rich data can reveal more subtle changes in patients’ behavioral and physiological characteristics, providing new ways to detect MCI anytime, anywhere. Therefore, we aimed to investigate the feasibility and validity of digital cognitive tests and physiological sensors applied to MCI assessment.MethodsWe collected photoplethysmography (PPG), electrodermal activity (EDA) and electroencephalogram (EEG) signals from 120 participants (61 MCI patients, 59 healthy controls) during rest and cognitive testing. The features extracted from these physiological signals involved the time domain, frequency domain, time-frequency domain and statistics. Time and score features during the cognitive test are automatically recorded by the system. In addition, selected features of all modalities were classified by tenfold cross-validation using five different classifiers.ResultsThe experimental results showed that the weighted soft voting strategy combining five classifiers achieved the highest classification accuracy (88.9%), precision (89.9%), recall (88.2%), and F1 score (89.0%). Compared to healthy controls, the MCI group typically took longer to recall, draw, and drag. Moreover, during cognitive testing, MCI patients showed lower heart rate variability, higher electrodermal activity values, and stronger brain activity in the alpha and beta bands.DiscussionIt was found that patients’ classification performance improved when combining features from multiple modalities compared to using only tablet parameters or physiological features, indicating that our scheme could reveal MCI-related discriminative information. Furthermore, the best classification results on the digital span test across all tasks suggest that MCI patients may have deficits in attention and short-term memory that came to the fore earlier. Finally, integrating tablet cognitive tests and wearable sensors would provide a new direction for creating an easy-to-use and at-home self-check MCI screening tool.

Breast cancer is one of the most common cancer types which is described as the leading cause of cancer death in women. After competitive endogenous RNA (ceRNA) hypothesis was proposed, this triple regulatory network has been observed in various cancers, and increasing evidences reveal that ceRNA network plays a significant role in the migration, invasion, proliferation of cancer cells. In the current study, our target is to construct a CD24-associated ceRNA network, and to further identify key prognostic biomarkers in breast cancer. Using the transcriptom profiles from TCGA database, we performed a comprehensive analysis between CD24high tumor samples and CD24low tumor samples, and identified 132 DElncRNAs, 602 DEmRNAs and 26 DEmiRNAs. Through comprehensive analysis, RP1-228H13.5/miR-135a-5p/BEND3 and SIM2 were identified as key CD24-associated biomarkers, which exhibited highly significance with overall survival, immune microenvironment as well as clinical features. To sum up the above, the current study constructed a CD24-associated ceRNA network, and RP1-228H13.5/miR-135a-5p/BEND3 and SIM2 axis worked as a potential therapeutic target and a predictor for BRCA diagnosis and prognosis.

Background Long non-coding RNA X-inactive specific transcript (XIST) regulates the progression of a variety of tumors, including osteosarcoma. Bone marrow mesenchymal stem cells (BMSCs) can be recruited into osteosarcoma tissue and affect the progression by secreting exosomes. However, whether BMSCs derived exosomes transmit XIST to regulate the growth and metastasis of osteosarcoma and the related mechanism are still unclear. Method In this study, BMSCs derived exosomes were used to treat human osteosarcoma cells MG63 and 143B, and the level of XIST in BMSCs was intervened by siRNA. CCK-8, EdU, transwell assays were used to analyze the changes of cell proliferation, migration and invasion. Bioinformatics analysis, RNA pulldown and dual-luciferase reporter gene assays validated the targeted relationship of XIST with miR-655 and the interaction between miR-655 and ACLY 3’-UTR. 143B/LUC cell line was used to establish an animal model of in situ osteosarcoma to verify the found effects of XIST on osteosarcoma. Oil Red O staining, Western blot and so on were used to detect the changes of lipid deposition and protein expression. Results It was found that BMSCs derived exosomes promoted the proliferation, migration and invasion of osteosarcoma cells, and the down-regulation of XIST inhibited this effect. miR-655 mediated the role of BMSCs derived exosomal XIST in promoting the progression of osteosarcoma and down-regulation of miR-655 could reverse the effects of inhibiting XIST on the proliferation, migration and invasion of osteosarcoma cells. Meanwhile, animal level results confirmed that BMSCs derived exosomal XIST could promote osteosarcoma growth and lung metastasis by combining with miR-655. In-depth mechanism study showed that BMSCs derived exosomal XIST combined with miR-655 to increase the protein level of ACLY, which led to lipid deposition and activate β-catenin signal to promote the proliferation, migration and invasion of osteosarcoma cells. Conclusion This study showed that BMSCs derived exosomal XIST could enter osteosarcoma cells, bind and down-regulates the level of miR-655, resulting in an increase in the level of ACLY, thus increasing the lipid deposition and the activity of β-catenin signal to promote the growth and metastasis of osteosarcoma.

Background: The GINS complex, composed of GINS1/2/3/4 subunits, is an essential structure of Cdc45-MCM-GINS (CMG) helicase and plays a vital role in establishing the DNA replication fork and chromosome replication. Meanwhile, GINS genes have been associated with the poor prognosis of various malignancies. However, the abnormal expression of GINS genes and their diagnostic and prognostic value in sarcomas (SARC) remain unclear.Methods: Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier Plotter, Cancer cell line encyclopedia (CCLE), The University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN), R studio, and Tumor Immune Estimation Resource (TIMER) were used to analyze the expression profiles, prognostic value, biological function, ceRNA, and immune infiltration associated with GINS genes in sarcomas.Results: We found that GINS1/2/3/4 genes exhibited significantly upregulated transcription levels in SARC samples compared to non-tumor tissues and exhibited high expression levels in sarcoma cell lines. In addition, SARC patients with increased expression levels of GINS1/2/3/4 showed poorer survival rates. Immune infiltration analysis showed that GINS subunits were closely associated with the infiltration of immune cells in sarcomas.Conclusion: Our research identified GINS subunits as potential diagnostic and prognostic biological targets in SARC and elucidated their underlying effects in the genesis and progression of SARC. These results may provide new opportunities and research directions for targeted sarcoma therapy.

Subtle changes in fine motor control and quantitative electroencephalography (qEEG) in patients with mild cognitive impairment (MCI) are important in screening for early dementia in primary care populations. In this study, an automated, non-invasive and rapid detection protocol for mild cognitive impairment based on handwriting kinetics and quantitative EEG analysis was proposed, and a classification model based on a dual fusion of feature and decision layers was designed for clinical decision-marking. Seventy-nine volunteers (39 healthy elderly controls and 40 patients with mild cognitive impairment) were recruited for this study, and the handwritten data and the EEG signals were performed using a tablet and MUSE under four designed handwriting tasks. Sixty-eight features were extracted from the EEG and handwriting parameters of each test. Features selected from both models were fused using a late feature fusion strategy with a weighted voting strategy for decision making, and classification accuracy was compared using three different classifiers under handwritten features, EEG features and fused features respectively. The results show that the dual fusion model can further improve the classification accuracy, with the highest classification accuracy for the combined features and the best classification result of 96.3% using SVM with RBF kernel as the base classifier. In addition, this not only supports the greater significance of multimodal data for differentiating MCI, but also tests the feasibility of using the portable EEG headband as a measure of EEG in patients with cognitive impairment.

Jellyfish envenomation is a common medical problem in many countries. However, the myotoxicity and effector molecules of scyphozoan venoms remain uninvestigated. Here, we present the myotoxicity of nematocyst venom from Nemopilema nomurai (NnNV), a giant venomous scyphozoan from China, for the first time, using in vivo models with inhibitors. NnNV was able to induce remarkable myotoxicity including significant muscle swelling, increasing the content of CK and LDH in serum, stimulating inflammation of muscle tissue, and destroying the structure of muscle tissue. In addition, the metalloproteinase inhibitors BMT and EDTA significantly reduced the myotoxicity induced by NnNV. Moreover, BMT and EDTA could decrease the inflammatory stimulation and necrosis of muscle tissue caused by the venom. These observations suggest that the metalloproteinase components of NnNV make a considerable contribution to myotoxicity. This study contributes to understanding the effector molecules of muscle injury caused by jellyfish stings and suggests a new idea for the treatment of scyphozoan envenomation.

Background: Soft tissue sarcoma is among the most challenging malignancies for clinicians and associated with poor prognosis. Former studies have revealed that cancer-associated fibroblasts (CAFs) are involved in tumor development, migration, invasion and metastasis.Methods: DEGs and WGCNA were employed to obtain significant CAFs-related genes for constructing the signature. Somatic mutation, immune status, immune checkpoints and chemotherapy sensitivity were applied to define the characteristics of the identified signature. Differentially expressed genes between the distinct groups and WGCNA were employed to obtain CAFs score of each patient. Results: 35 genes were identified as CAFs-related genes in soft tissue sarcoma samples. Then, 12 CAFs-related genes were associated with overall survival in univariate Cox regression analysis and K-M method. The five genes signature was constructed based on the result from the LASSO regression analysis in train cohort. K-M curve showed that patients in the low CAFs score group had better survival, with immune infiltration and function significantly increased (P This study strongly revealed the indispensable role of CAFs in soft tissue sarcoma and constructed the prognostic signature including five CAFs-related genes.

Background: Osteoarthritis (OA) is a degenerative disease which serious affects patients. Ligusticum chuanxiong (CX) has been shown to have a certain curative effect on osteoarthritis in traditional Chinese medicine therapy. This study is based on network pharmacology and molecular docking technology to explore the potential mechanism of CX.Methods: Components of CX to treat osteoarthritis were screened in the TCMSP database and targets were predicted by the PharmMapper database, the osteoarthritis targets were collected from the GeneCards database, and intersection genes were found to be the possible targets of CX anti-OA. The STRING database and Cytoscape software were utilized for protein-protein interaction analysis and further screening of core targets. The Metascape database was used for KEGG and GO enrichment analyses. Then, the top 10 pathways were selected to construct “drug-compound-target-pathway-disease” network analysis. Finally, molecular docking was used to analyze the binding affinity of seven compounds with core targets and TNF-α.Results: Seven compounds with 253 non-repetitive targets of CX were screened from the TCMSP database and 60 potential intersection targets of CX anti-OA were found. PPI network analysis showed that the core targets were ALB, AKT1, IGF1, CASP3, MAPK1, ANXA5, and MAPK14, while GO and KEGG pathway enrichment analyses showed that the relevant biological processes involved in the treatment of osteoarthritis by CX might include the MAPK cascade and reactive oxygen species metabolic process. The KEGG pathway analysis result was mainly associated with the MAPK signaling pathway and PI3K-AKT signaling pathway. We further docked seven ingredients with MAPK1 and MAPK14 enriched in the MAPK pathway, and TNF-α as the typical inflammatory cytokine. The results also showed good binding affinity, especially FA, which may be the most important component of CX anti-OA.Conclusion: Our research revealed the potential mechanism of CX in the treatment of OA, and our findings can also pave the way for subsequent basic experimental verification and a new research direction.

Jellyfish Cyanea nozakii venom is a complex mixture of various toxins, most of which are proteinous biological macromolecules and are considered to be responsible for clinical symptoms or even death after a severe sting. Previous transcriptome and proteome analysis identified hundreds of toxins in the venom, including hemolysins, C-type lectin, phospholipase A

Osteoporosis is a complex multifactorial disorder linked to various risk factors and medical conditions. Bone marrow-derived mesenchymal stem cell (BMSC) dysfunction potentially plays a critical role in osteoporosis pathogenesis. Herein, the study identified that miR-4739 was upregulated in BMSC cultures harvested from osteoporotic subjects. BMSCs were isolated from normal and osteoporotic bone marrow tissues and identified for their osteogenic differentiation potential. In osteoporotic BMSCs, miR-4739 overexpression significantly inhibited cell viability, osteoblast differentiation, mineralized nodule formation, and heterotopic bone formation, whereas miR-4739 inhibition exerted opposite effects. Through direct binding, miR-4739 inhibited distal-less homeobox 3 (DLX3) expression. In osteoporotic BMSCs, DLX3 knockdown also inhibited BMSC viability and osteogenic differentiation. Moreover, DLX3 knockdown partially attenuated the effects of miR-4739 inhibition upon BMSCs. Altogether, the miR-4739/DLX3 axis modulates the capacity of BMSCs to differentiate into osteoblasts, which potentially plays a role in osteoporosis pathogenesis. The in vivo and clinical functions of the miR-4739/DLX3 axis require further investigation.

Magnesium (Mg) and its alloys as a type of different biodegradable materials have been used in the musculoskeletal field because of their excellent biocompatibility, biodegradability and mechanical properties similar to bone; besides, Mg could promote osteoblast differentiation in vitro and induce the formation of new bone in vivo. In the present study, we prepared the extracts of Mg–Zn–Mn alloy and examined their effects on the angiogenesis of human umbilical vein endothelial cells (HUVECs). In the present study, we prepared Mg–Zn–Mn alloy extracts of different concentrations and cultured HUVECs with these extracts. The DNA synthesis capacity, the cell viability, and the tube formation capacity of HUVECs could be significantly induced by 6.25% Mg alloy extract. In the meantime, the ratios of p-FGFR/FGFR, p-PI3K/PI3K, and p-AKT/AKT were significantly increased by 6.25% Mg alloy extract treatment, while decreased by FGFR/FGFR signaling pathway inhibitor BFJ398, indicating that 6.25% Mg alloy extract could promote the angiogenesis of HUVECs via activating FGF/FGFR signaling pathway. In conclusion, these data indicate that 6.25% Mg–Zn–Mn alloy extract induces the angiogenesis of HUVECs via FGF signaling pathway. Further in vivo experiments are needed to further confirm the present in vitro findings.

Melanoma is the most common cancer of the skin, associated with a worse prognosis and distant metastasis. Epithelial–mesenchymal transition (EMT) is a reversible cellular biological process that plays significant roles in diverse tumor functions, and it is modulated by specific genes and transcription factors. The relevance of EMT-related lncRNAs in melanoma has not been determined. Therefore, RNA expression data and clinical features were collected from the TCGA database (N = 447). Melanoma samples were randomly assigned into the training (315) and testing sets (132). An EMT-related lncRNA signature was constructed via comprehensive analyses of lncRNA expression level and corresponding clinical data. The Kaplan-Meier analysis showed significant differences in overall survival in patients with melanoma in the low and high-risk groups in two sets. Receiver operating characteristic (ROC) curves were used to measure the performance of the model. Cox regression analysis indicated that the risk score was an independent prognostic factor in two sets. Besides, a nomogram was constructed based on the independent variables. Gene Set Enrichment Analysis (GSEA) was applied to evaluate the potential biological functions in the two risk groups. Furthermore, the melanoma microenvironment was evaluated using ESTIMATE and CIBERSORT algorithms in the risk groups. This study indicates that EMT-related lncRNAs can function as potential independent prognostic biomarkers for melanoma survival.

Background: Synovial sarcoma is an uncommon soft sarcoma that lacks prognostic prediction models. The nomograms were employed to predict patients’ survival of synovial sarcoma. Methods: Materials collected from 1941 synovial sarcoma cases in the SEER database were analyzed. We employed univariate and multivariate cox analyses to identify the independent prognostic variables. Based on these outcomes, the nomograms were built for predicting 1-, 3-, and 5- year overall survival rate and disease-specific survival rate and then validated in external dataset. C-indices, calibration plots and ROC curves were applied to assess nomogram accuracy. Results: Patients were randomly classified into the training (n=1361) and testing (n=580) cohorts. Age, race, sex, primary anatomic site, chemotherapy, subtypes, surgery, SEER historic stage and tumor size were identified as independent prognostic variables (PConclusion: we constructed the reliable nomograms for synovial sarcoma patients to predict overall and disease-specific survival, which can offer precise and personalized survival prediction.

The infrared reflective layer is one of the most important components of solar selective absorbing coatings (SSACs). The low infrared emissivity of the infrared reflective layer is necessary to reduce the energy losses caused by the thermal radiation from the SSACs. Also, the thermal stability of the infrared reflective layer has a crucial impact on the thermal stability of the entire coatings. In this study, a series of Mo films, as the infrared reflective layer, were deposited on stainless steel (SS) or glass substrates by DC magnetron sputtering. The effects of sputtering parameters on crystal structure, surface morphologies, film resistivity, and infrared emissivity of the Mo films are systematically investigated. The lowest infrared emissivity of the prepared Mo films is 0.06, which can be obtained by optimizing the deposition parameters. And the emissivity could be further decreased to 0.03 by annealing treatment. The insertion of a TiN layer between the Mo layer and the SS substrate can effectively inhibit the elemental diffusion from the SS substrate to the Mo film in vacuum until 700 °C, which improves effectively the operating temperature of the Mo film as an infrared reflective layer in SSAC.

All the identified proteins in the proteome analysis of the antivenom for Nemopilema nomurai.

In the era of Internet finance, commercial banks must follow the characteristics of information technology development, create a new development model and coping strategies. Only in this way can commercial banks always occupy the dominant position of market economy to ensure that China’s economy is always in rapid development. Under the rapid development of third-party payment and Internet big data payment credit, the traditional commercial banking business has been greatly restricted. The traditional bank development model can no longer meet the needs of small and medium-sized enterprises and people. Compared with the traditional commercial banks, the Internet payment software headed by Alipay must persist in reform and innovation and take the advantages of Internet technology in the face of the challenges of private Internet finance. It is necessary for them to complete the transformation between traditional commercial banks and Internet commercial banks.