Role of mesenchymal stem cell-derived exosomes in the regeneration of different tissues.

Exosomes are nanovesicles with multiple components used in several applications. Mesenchymal stem cells (MSCs) are well known for their great potential in clinical applications. MSC-derived exosomes (MSC-Exos) have been shown to mediate tissue regeneration in various diseases, including neurological, autoimmune, and inflammatory diseases, cancer, ischemic heart disease, lung injury, and liver fibrosis. They can modulate the immune response by interacting with immune effector cells in the presence of anti-inflammatory compounds and are involved in intercellular communication through various types of cargo. This review summarizes the MSC-Exos-mediated tissue regeneration in various diseases, including neurological, cardiovascular, liver, kidney, articular cartilage, and oral tissue applications. In addition, we discuss the challenges and prospects of MSC-Exos in tissue regeneration.

Changes in Diversity and Composition of Rhizosphere Bacterial and Fungal Community between Resistant and Susceptible Pakchoi under Plasmodiophora brassicae.

Plasmodiophora brassicae (P. brassicae) is a soil-born pathogen worldwide and can infect most cruciferous plants, which causes great yield decline and economic losses. It is not well known how microbial diversity and community composition change during P. brassicae infecting plant roots. Here, we employed a resistant and a susceptible pakchoi cultivar with and without inoculation with P. brassicae to analyze bacterial and fungal diversity using 16S rRNA V3-V4 and ITS_V1 regions, respectively. 16S rRNA V3-V4 and ITS_V1 regions were amplified and sequenced separately. Results revealed that both fungal and bacterial diversity increased, and composition was changed in the rhizosphere soil of the susceptible pakchoi compared with the resistant cultivar. In the four groups of R_mock, S_mock, R_10d, and S_10d, the most relatively abundant bacterium and fungus was Proteobacteria, accounting for 61.92%, 58.17%, 48.64%, and 50.00%, respectively, and Ascomycota, accounting for 75.11%, 63.69%, 72.10%, and 90.31%, respectively. A total of 9488 and 11,914 bacteria were observed uniquely in the rhizosphere soil of resistant and susceptible pakchoi, respectively, while only 80 and 103 fungi were observed uniquely in the correlated soil. LefSe analysis showed that 107 and 49 differentially abundant taxa were observed in bacteria and fungi. Overall, we concluded that different pakchoi cultivars affect microbial diversity and community composition, and microorganisms prefer to gather around the rhizosphere of susceptible pakchoi. These findings provide a new insight into plant-microorganism interactions.

A robust seizure detection and prediction method with feature selection and spatio-temporal casual neural network model.

Objective.Epilepsy is a fairly common condition that affects the brain and causes frequent seizures. The sudden and recurring epilepsy brings a series of safety hazards to patients, which seriously affects the quality of their life. Therefore, real-time diagnosis of electroencephalogram (EEG) in epilepsy patients is of great significance. However, the conventional methods take in a tremendous amount of features to train the models, resulting in high computation cost and low portability. Our objective is to propose an efficient, light and robust seizure detecting and predicting algorithm.Approach.The algorithm is based on an interpretative feature selection method and spatial-temporal causal neural network (STCNN). The feature selection method eliminates the interference factors between different features and reduces the model size and training difficulties. The STCNN model takes both temporal and spatial information to accurately and dynamically track and diagnose the changing of the features. Considering the differences between medical application scenarios and patients, leave-one-out cross validation (LOOCV) and cross-patient validation (CPV) methods are used to conduct experiments on the dataset collected at the Children's Hospital Boston (CHB-MIT), Siena and Kaggle competition datasets.Main results.In LOOCV-based method, the detection accuracy and prediction sensitivity have been improved. A significant improvement is also achieved in the CPV-based method.Significance.The experimental results show that our proposed algorithm exhibits superior performance and robustness in seizure detection and prediction, which indicates it has higher capability to deal with different and complicated clinical situations.

Role of exosomes in the development, diagnosis, prognosis and treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. It is characterized by occult onset resulting in most patients being diagnosed at advanced stages and with poor prognosis. Exosomes are nanoscale vesicles with a lipid bilayer envelope released by various cells under physiological and pathological conditions, which play an important role in the biological information transfer between cells. There is growing evidence that HCC cell-derived exosomes may contribute to the establishment of a favorable microenvironment that supports cancer cell proliferation, invasion, and metastasis. These exosomes not only provide a versatile platform for diagnosis but also serve as a vehicle for drug delivery. In this paper, we review the role of exosomes involved in the proliferation, migration, and metastasis of HCC and describe their application in HCC diagnosis and treatment. We also discuss the prospects of exosome application in HCC and the research challenges.

Role of CD147 in the development and diagnosis of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, and the third leading cause of cancer-related deaths worldwide. HCC is characterized by insidious onset, and most patients are diagnosed at an advanced stage with a poor prognosis. Identification of biomarkers for HCC onset and progression is imperative to development of effective diagnostic and therapeutic strategies. CD147 is a glycoprotein that is involved in tumor cell invasion, metastasis and angiogenesis through multiple mechanisms. In this review, we describe the molecular structure of CD147 and its role in regulating HCC invasion, metastasis and angiogenesis. We highlight its potential as a diagnostic and therapeutic target for HCC.

Process Optimization of Dual-Liquid Casting and Interfacial Strength-Toughness of the Produced LAS/HCCI Bimetal.

The pouring time interval is the decisive factor of dual-liquid casting for bimetallic productions. Traditionally, the pouring time interval is fully determined by the operator's experience and on-site observation. Thus, the quality of bimetallic castings is unstable. In this work, the pouring time interval of dual-liquid casting for producing low alloy steel/high chromium cast iron (LAS/HCCI) bimetallic hammerheads is optimized via theoretical simulation and experimental verification. The relevancies of interfacial width and bonding strength to pouring time interval are, respectively, established. The results of bonding stress and interfacial microstructure indicate that 40 s is the optimum pouring time interval. The effects of interfacial protective agent on interfacial strength-toughness are also investigated. The addition of the interfacial protective agent yields an increase of 41.5% in interfacial bonding strength and 15.6% in toughness. The optimum dual-liquid casting process is used to produce LAS/HCCI bimetallic hammerheads. Samples cut from these hammerheads show excellent strength-toughness (1188 Mpa for bonding strength and 17 J/cm2 for toughness). The findings could be a reference for dual-liquid casting technology. They are also helpful for understanding the formation theory of the bimetal interface.

IEF-CSNET: Information Enhancement and Fusion Network for Compressed Sensing Reconstruction.

The rapidly growing requirement for data has put forward Compressed Sensing (CS) to realize low-ratio sampling and to reconstruct complete signals. With the intensive development of Deep Neural Network (DNN) methods, performance in image reconstruction from CS measurements is constantly increasing. Currently, many network structures pay less attention to the relevance of before- and after-stage results and fail to make full use of relevant information in the compressed domain to achieve interblock information fusion and a great receptive field. Additionally, due to multiple resamplings and several forced compressions of information flow, information loss and network structure redundancy inevitably result. Therefore, an Information Enhancement and Fusion Network for CS reconstruction (IEF-CSNET) is proposed in this work, and a Compressed Information Extension (CIE) module is designed to fuse the compressed information in the compressed domain and greatly expand the receptive field. The Error Comprehensive Consideration Enhancement (ECCE) module enhances the error image by incorporating the previous recovered error so that the interlink among the iterations can be utilized for better recovery. In addition, an Iterative Information Flow Enhancement (IIFE) module is further proposed to complete the progressive recovery with loss-less information transmission during the iteration. In summary, the proposed method achieves the best effect, exhibits high robustness at this stage, with the peak signal-to-noise ratio (PSNR) improved by 0.59 dB on average under all test sets and sampling rates, and presents a greatly improved speed compared with the best algorithm.

MsVRL: Self-Supervised Multiscale Visual Representation Learning via Cross-Level Consistency for Medical Image Segmentation.

Automated medical image segmentation for organs or lesions plays an essential role in clinical diagnoses and treatment plannings. However, training an accurate and robust segmentation model is still a long-standing challenge due to the time-consuming and expertise-intensive annotations for training data, especially 3-D medical images. Recently, self-supervised learning emerges as a promising approach for unsupervised visual representation learning, showing great potential to alleviate the expertise annotations for medical images. Although global representation learning has attained remarkable results on iconic datasets, such as ImageNet, it can not be applied directly to medical image segmentation, because the segmentation task is non-iconic, and the targets always vary in physical scales. To address these problems, we propose a Multi-scale Visual Representation self-supervised Learning (MsVRL) model, to perform finer-grained representation and deal with different target scales. Specifically, a multi-scale representation conception, a canvas matching method, an embedding pre-sampling module, a center-ness branch, and a cross-level consistent loss are introduced to improve the performance. After pre-trained on unlabeled datasets (RibFrac and part of MSD), MsVRL performs downstream segmentation tasks on labeled datasets (BCV, spleen of MSD, and KiTS). Results of the experiments show that MsVRL outperforms other state-of-the-art works on these medical image segmentation tasks.

Application of arthroscopic system in the treatment of lactational breast abscess.

PURPOSE: Optimal treatment of breast abscesses has been controversial. Herein, we report an innovative method for the operative treatment of lactational mammary abscesses. METHODS: Nineteen lactating patients diagnosed with breast abscesses were enrolled in the study, and abscess debridement and drainage were performed using an arthroscopic system. The clinical characteristics of the patients were recorded to evaluate the feasibility, efficacy, and cosmetic results of arthroscopic surgery for breast abscesses. RESULTS: All 19 patients were cured and did not relapse within the 6-month-follow-up period. One patient stopped breastfeeding due to breast leakage. All patients were satisfied with the postoperative appearance of the breast. CONCLUSION: Arthroscopic debridement and drainage are effective treatment methods for lactational breast abscesses, with a high cure rate, few complications, and satisfactory cosmetic outcomes.

Track Fusion Fractional Kalman Filter for the Multisensor Descriptor Fractional Systems.

The purpose of this study was to investigate the state estimation problem for the multisensor descriptor fractional systems. Firstly, the descriptor fractional order system was transformed into two nondescriptor fractional order subsystem based on the singular value decomposition method; then, the descriptor fractional Kalman filters for the subsystems were proposed based on projection theory, which effectively solved the state estimation problem of the descriptor fractional order system with singular matrix; on this basis, the track fusion fractional Kalman filter of the multisensor descriptor fractional system is proposed by using the track fusion algorithm. The state estimation accuracy of multisensor descriptor fractional order systems is greatly improved. Simulation results show the effectiveness of the proposed algorithm.

Vitamin D enhances the sensitivity of breast cancer cells to the combination therapy of photodynamic therapy and paclitaxel.

PURPOSE: Given that Vitamin D (VD) has been confirmed to reinforce the toxic effects of 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) towards breast cancer, this study was designed to decipher the combined effects of VD, ALA-PDT and paclitaxel (PTX). METHODS: Thiazolyl blue tetrazolium bromide assay was conducted to gauge the viability of breast cancer cells treated with ALA-PDT and PTX alone or in combination. The cell migration, invasion and apoptosis were measured by wound healing, transwell and flow cytometry assays, respectively. Xenograft tumor models were established and tumor volume and weight were recorded. The expression of Bcl-2, Bax and cleaved caspase-3 in cells and tumor tissues was determined by western blot assay. RESULTS: Both ALA-PDT and PTX alone inhibited viability in a dose-dependent manner, blocked migration and invasion, boosted apoptosis, down-regulated Bcl-2 expression and upregulated the expression of Bax and cleaved caspase-3 in breast cancer cells. More significant effects on the above-mentioned factors were induced by ALA-PDT and PTX in combination. Moreover, ALA-PDT and PTX in combination also suppressed the growth of xenograft tumors and Bcl-2 expression while promoting the expression of Bax and cleaved caspase-3 in tumors. In contrast, VD had no effect on tumor growth and the expression of Bcl-2, Bax and cleavedcaspase-3, but intensified the combined effects of ALA-PDT and PTX. CONCLUSION: VD could enhance the therapeutic effects of ALA-PDT combined with PTX on tumor growth and cell apoptosis.

Chloroplast genome sequence of Chongming lima bean (Phaseolus lunatus L.) and comparative analyses with other legume chloroplast genomes.

BACKGROUND: Lima bean (Phaseolus lunatus L.) is a member of subfamily Phaseolinae belonging to the family Leguminosae and an important source of plant proteins for the human diet. As we all know, lima beans have important economic value and great diversity. However, our knowledge of the chloroplast genome level of lima beans is limited. RESULTS: The chloroplast genome of lima bean was obtained by Illumina sequencing technology for the first time. The Cp genome with a length of 150,902 bp, including a pair of inverted repeats (IRA and IRB 26543 bp each), a large single-copy (LSC 80218 bp) and a small single-copy region (SSC 17598 bp). In total, 124 unique genes including 82 protein-coding genes, 34 tRNA genes, and 8 rRNA genes were identified in the P. lunatus Cp genome. A total of 61 long repeats and 290 SSRs were detected in the lima bean Cp genome. It has a typical 50 kb inversion of the Leguminosae family and an 70 kb inversion to subtribe Phaseolinae. rpl16, accD, petB, rsp16, clpP, ndhA, ndhF and ycf1 genes in coding regions was found significant variation, the intergenic regions of trnk-rbcL, rbcL-atpB, ndhJ-rps4, psbD-rpoB, atpI-atpA, atpA-accD, accD-psbJ, psbE-psbB, rsp11-rsp19, ndhF-ccsA was found in a high degree of divergence. A phylogenetic analysis showed that P. lunatus appears to be more closely related to P. vulgaris, V.unguiculata and V. radiata. CONCLUSIONS: The characteristics of the lima bean Cp genome was identified for the first time, these results will provide useful insights for species identification, evolutionary studies and molecular biology research.

Flammulina velutipes polysaccharide improves C57BL/6 mice gut health through regulation of intestine microbial metabolic activity.

Flammulina velutipes polysaccharides (FVP) can improve gut health through gut microbiota and metabolism regulation. In this study, the 28-days fed experiment was used to investigate gut microbime and metabolic profiling induced by FVP. After treatment, intestinal tissue section showed the higher villus height and villus height/crypt depth (V/C) value in FVP-treated group. The 16 s rRNA gene sequencing revealed microbiota composition alteration caused by FVP, as the Firmicutes phylum increased while Bacteroidetes phylum slightly decreased. The metabolic profiling was detected by LC/MS and results showed 56 and 99 compounds were dramatically changed after FVP treatment in positive and negative ion mode, respectively. Annotation in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways displayed the adjustment of energy metabolism, amino acid metabolism, nucleotide metabolism and other related basic pathways after FVP treatment. Our study suggested that FVP can be developed as a dietary supplement for intestine health promotion.

Transcriptome profiling and gene expression analyses of eggplant (Solanum melongena L.) under heat stress.

Global warming induces heat stress in eggplant, seriously affecting its quality and yield. The response to heat stress is a complex regulatory process; however, the exact mechanism in eggplant is unknown. We analyzed the transcriptome of eggplant under different high-temperature treatments using RNA-Seq technology. Three libraries treated at high temperatures were generated and sequenced. There were 40,733,667, 40,833,852, and 40,301,285 clean reads with 83.98%, 79.69%, and 84.42% of sequences mapped to the eggplant reference genome in groups exposed to 28°C (CK), 38°C (T38), and 43°C (T43), respectively. There were 3,067 and 1,456 DEGs in T38 vs CK and T43 vs CK groups, respectively. In these two DEG groups, 315 and 342 genes were up- and down-regulated, respectively, in common. Differential expression patterns of DEGs in antioxidant enzyme systems, detoxication, phytohormones, and transcription factors under heat stress were investigated. We screened heat stress-related genes for further validation by qRT-PCR. Regulation mechanisms may differ under different temperature treatments, in which heat shock proteins and heat stress transcription factors play vital roles. These results provide insight into the molecular mechanisms of the heat stress response in eggplant and may be useful in crop breeding.

Application of the Nano-Drug Delivery System in Treatment of Cardiovascular Diseases.

Cardiovascular diseases (CVDs) have become a serious threat to human life and health. Though many drugs acting via different mechanism of action are available in the market as conventional formulations for the treatment of CVDs, they are still far from satisfactory due to poor water solubility, low biological efficacy, non-targeting, and drug resistance. Nano-drug delivery systems (NDDSs) provide a new drug delivery method for the treatment of CVDs with the development of nanotechnology, demonstrating great advantages in solving the above problems. Nevertheless, there are some problems about NDDSs need to be addressed, such as cytotoxicity. In this review, the types and targeting strategies of NDDSs were summarized, and the new research progress in the diagnosis and therapy of CVDs in recent years was reviewed. Future prospective for nano-carriers in drug delivery for CVDs includes gene therapy, in order to provide more ideas for the improvement of cardiovascular drugs. In addition, its safety was also discussed in the review.

STAT3/c-Myc Axis-Mediated Metabolism Alternations of Inflammation-Related Glycolysis Involve with Colorectal Carcinogenesis.

Chronic inflammation is a major driving factor for the development of colitis-associated cancer (CAC). It is extensively acknowledged that patients who have long-standing inflammation bowel disease are at high risk for developing CAC. However, the metabolic alteration by which chronic intestinal inflammation promotes colorectal cancer is unclear. In the present study, we constructed dextran sulfate sodium (DSS)-induced colitis mouse model to uncover possible alterations in the metabolism indexes. Interestingly, after DSS diet administration, the expression of metabolism indexes and c-Myc increased. Moreover, in vitro, we treated cells with IL-6 to simulate inflammatory microenvironment and found that glucose uptake, lactate production, and lactate dehydrogenase activity increased dramatically, mirroring what were observed in vivo. In addition, the associative inhibition of STAT3 and c-Myc could significantly block the expression of metabolic enzymes. With the inhibition of STAT3/c-Myc signaling, meanwhile, the upregulation of both cell glucose uptake and lactate production by IL-6 pretreatment was reduced simultaneously. Thus, our study indicates that inflammation could induce metabolic disorder by promoting STAT3 signaling and c-Myc activity. Collectively, we find that metabolic disruptions triggered by inflammatory signaling are associated with tumorigenesis via the STAT3/c-Myc axis.

Long Noncoding RNA MRPL39 Inhibits Gastric Cancer Proliferation and Progression by Directly Targeting miR-130.

BACKGROUND: Gastric cancer (GC) is one of the most prevalent malignant tumors displaying both high incidence and mortality throughout much of the world. Recently, long noncoding RNAs (lncRNAs) have been implicated in the development and progression of GC. MATERIALS AND METHODS: In the present study, we investigated the biological function and molecular mechanisms of lncRNA MRPL39 in GC. RESULTS: We found that MRPL39 was significantly downregulated in GC tissues and cell lines and that its expression level was negatively associated with carcinoma size, tumor, lymph node, metastasis (TNM) stage, and lymphatic metastasis. Patients with low MRPL39 expression levels revealed a short overall and disease-free survival period. Over-expression of MRPL39 in the GC cell lines BGC823 and SGC-7901 inhibited cell growth, proliferation, migration, and invasion. MiR-130, a putative target gene of MRPL39, displayed an inverse association with the expression of MRPL39 in GC tissues and cell lines. Moreover, a luciferase assay demonstrated a direct binding between the miR-130 and MRPL39, and the reintroduction of miR-130 abrogated the anti-tumor effect of MRPL39 on GC cells. CONCLUSION: Taken together, these findings indicate that MRPL39 serves as a tumor suppressor by directly targeting miR-130 in GC, which suggests that it might be a novel biomarker in the diagnosis and prognosis of GC.

A single-camera gaze tracking system under natural light.

Gaze tracking is a human-computer interaction technology, and it has been widely studied in the academic and industrial fields. However, constrained by the performance of the specific sensors and algorithms, it has not been popularized for everyone. This paper proposes a single-camera gaze tracking system under natural light to enable its versatility. The iris center and anchor point are the most crucial factors for the accuracy of the system. The accurate iris center is detected by the simple active contour snakuscule, which is initialized by the prior knowledge of eye anatomical dimensions. After that, a novel anchor point is computed by the stable facial landmarks. Next, second-order mapping functions use the eye vectors and the head pose to estimate the points of regard. Finally, the gaze errors are improved by implementing a weight coefficient on the points of regard of the left and right eyes. The feature position of the iris center achieves an accuracy of 98.87% on the GI4E database when the normalized error is lower than 0.05. The accuracy of the gaze tracking method is superior to the-state-of-the-art appearance-based and feature- based methods on the EYEDIAP database.

Edaravone protects against oxygen-glucose-serum deprivation/restoration-induced apoptosis in spinal cord astrocytes by inhibiting integrated stress response.

We previously found that oxygen-glucose-serum deprivation/restoration (OGSD/R) induces apoptosis of spinal cord astrocytes, possibly via caspase-12 and the integrated stress response, which involves protein kinase R-like endoplasmic reticulum kinase (PERK), eukaryotic initiation factor 2-alpha (eIF2α) and activating transcription factor 4 (ATF4). We hypothesized that edaravone, a low molecular weight, lipophilic free radical scavenger, would reduce OGSD/R-induced apoptosis of spinal cord astrocytes. To test this, we established primary cultures of rat astrocytes, and exposed them to 8 hours/6 hours of OGSD/R with or without edaravone (0.1, 1, 10, 100 µM) treatment. We found that 100 µM of edaravone significantly suppressed astrocyte apoptosis and inhibited the release of reactive oxygen species. It also inhibited the activation of caspase-12 and caspase-3, and reduced the expression of homologous CCAAT/enhancer binding protein, phosphorylated (p)-PERK, p-eIF2α, and ATF4. These results point to a new use of an established drug in the prevention of OGSD/R-mediated spinal cord astrocyte apoptosis via the integrated stress response.

Anthelminthic drug niclosamide sensitizes the responsiveness of cervical cancer cells to paclitaxel via oxidative stress-mediated mTOR inhibition.

Drug repurposing represents an alternative therapeutic strategy to cancer treatment. The potent anti-cancer activities of a FDA-approved anthelminthic drug niclosamide have been demonstrated in various cancers. However, whether niclosamide is active against cervical cancer is unknown. In this study, we investigated the effects of niclosamide alone and its combination with paclitaxel in cervical cancer in vitro and in vivo. We found that niclosamide significantly inhibited proliferation and induced apoptosis of a panel of cervical cancer cell lines, regardless of their cellular origin and genetic pattern. Niclosamide also inhibited tumor growth in cervical cancer xenograft mouse model. Importantly, niclosamide significantly enhanced the responsiveness of cervical cancer cell to paclitaxel. We further found that niclosamide induced mitochondrial dysfunctions via inhibiting mitochondrial respiration, complex I activity and ATP generation, which led to oxidative stress. ROS scavenge agent N-acetyl-l-cysteine (NAC) completely reversed the effects of niclosamide in increasing cellular ROS, inhibiting proliferation and inducing apoptosis, suggesting that oxidative stress induction is the mechanism of action of niclosamide in cervical cancer cells. In addition, niclosamide significantly inhibited mammalian target of rapamycin (mTOR) signaling pathway in cervical cancer cells and its inhibitory effect on mTOR is modulated by oxidative stress. Our work suggests that niclosamide is a useful addition to the treatment armamentarium for cervical cancer and induction of oxidative stress may be a potential therapeutic strategy in cervical cancer.