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Background:The study was conducted to find out the candidate microRNA (miRNA) and genes that regulate the sperm motility of Yili goose through small RNA sequencing of testicular tissue of Yili goose, and provide a theoretical basis for the study of the regulation mechanism of sperm motility of Yili goose gander. Results:In this study, five male geese with high sperm motility and five male geese with low sperm motility were slaughtered to obtain their testis tissues for small RNA sequencing, and biological information methods were used for data analysis. The results showed that a total of 1575 known miRNAs and 68 novel miRNAs were identified in the testis tissue of Yili goose, and 71 differentially expressed miRNAs and 660 differentially expressed genes were screened. GO functional analysis showed that miRNAs target genes were mainly involved in terms such as binding, kinase activity, structural constituent of cytoskeleton and intermediate filament cytoskeleton. KEGG functional analysis showed that miRNAs target genes were significantly enriched in arginine and proline metabolism, glycolysis / gluconeogenesis, fructose and mannose metabolism and beta-Alanine metabolism and other pathways. miRNAs-mRNAs interaction network suggests cfa-miR-140/gga-miR-140-3p/ola-miR-140-3p-NKAIN3, cfa-let-7d-BTG1 and dre-miR-145-5p/mmu-miR -145a-5p-Clec2e may play an important role in testis development and spermatogenesis. Conclusions:The results of this study suggest that the sperm motility of Yili goose may be regulated by different miRNAs, and the target genes are significantly enriched in pathways related to sperm metabolism, indicating that miRNAs affect the sperm motility of Yili goose by regulating the metabolic process of sperm and the expression of related genes. This study can provide a reference for revealing the regulation mechanism of Yili goose sperm motility at the molecular level.

Currently, abnormally elevated rail potential exists in the DC traction power system, which greatly threatens the safe operation of the line. In order to realize the reflux safety, timetable optimi...

The failure to treat and control the growth of metastases is the main cause of death in breast cancer (BC) patients. Compared to the traditional method of analyzing circulating tumor DNA (ctDNA), capturing intact circulating tumor cells (CTCs) allows us to more accurately characterize mutations and identify suitable targeted therapies. We used CellCollector to collect peripheral CTCs. Thirty metastatic breast cancer (MBC) patients were enrolled, and 17 were analyzed with next-generation sequencing (NGS) methods. Clinical characteristics were analyzed along with the CTCs enumeration and detection rates. Whole-genome amplification (WGA) was used to amplify the CTC genomic DNA of 127 genes. Patients younger than 45 years old, with brain metastasis, with three or more metastatic sites, or with HER2-positive had the highest number of CTCs collected. The CTCs detection rate was also correlated to the number of metastasis sites. Different metastasis sites such as the brain, viscus, bone, and soft tissue contained specific high-frequency gene mutations. AKT3, MYC, and NT5C2 mutations were only found in brain metastases. APC, BCL2L11, ESRP1, FLT3 mutations were only in the visceral metastases. KEAP1, KIT, MET were the specific mutation genes in patients with bone and soft tissue metastases. These findings provide evidence that we can detect gene mutation information for obtaining the biological characteristics by CTCs using CellCollector. Different metastasis sites contain specific high-frequency mutation genes, which provide guidance to the accurate gene therapy.

As one of the initiating DNA glycosylases in the base excision repair pathway, Uracil-DNA glycosylase (UDG) plays a pivotal role in maintaining genomic integrity. The abnormal expression of UDG in the organism is highly relevant to multiple diseases. Thus, rapid and sensitive detection of UDG activity is essential to aid early clinical diagnosis and biomedical research. Here we developed a rapid, sensitive and selective biosensor for UDG activity detection based on the substrate preference of Lambda exonuclease (λ exo). The protruding end in the substrate produced by UDG could be digested at a markedly high rate by λ exo, generating a detectable fluorescence signal. This proposed strategy for UDG detection exhibited high selectivity and high sensitivity (0.0001 U/mL) in a short time. It has also been successfully applied to detect UDG in real biological samples and the screening of UDG inhibitors.

We utilized albumin as a reducing agent to establish novel copper-based and pH-sensitive nanocarrier CuNPs with abundant Cu+, which can encapsulate histone deacetylase (HDAC) inhibitor vorinostat to form uniform and stable nanomedicine V-CuNPs for synergistic chromatin remodelling and chemodynamic therapy.

Radiotherapy (RT) is one of the most extensive and effective approaches available for clinical tumor treatment. However, tumor microenvironments including hypoxia and histone deacetylase (HDAC) overexpression could induce radiation resistance, leading to tumor recurrence. Herein, nanoparticles (CAT-SAHA@PLGA) encapsulating catalase and HDAC inhibitor SAHA exhibited protected catalytic activity of catalase and prolonged the pharmacokinetic exposure of the HDAC inhibitor. Overall, the established CAT-SAHA@PLGA nanoparticles could overcome radiation resistance by synergistically increasing tumor oxygenation and inhibiting HDAC activity.

Background: Breast cancer (BC) is the most frequently diagnosed cancer in women and is the second most common cancer among newly diagnosed cancers worldwide. Studies have shown that paired box 2 (PAX2) participates in the tumorigenesis of some cancer cells. However, the functions of PAX2 in the BC context are still unclear.Methods: Transcriptome expression profiles and clinicopathological information of BC were download from the TCGA database. Then the expression level and prognostic value in TCGA database were explored. Gene Set Enrichment Analysis (GSEA) and functional enrichment analysis were performed to investigate the functions and pathways of PAX2. Moreover, RT-qPCR was used to determine the expression of PAX2 in BC tissues, and the predictive value of PAX2 in clinical samples was assessed. CCK-8 assay was used to evaluate cell growth. The migration and invasion capacities of cells were assessed by wound healing assay and Transwell assay.Results: PAX2 was up-regulated in the TCGA-BC datasets. GSEA analysis suggested that PAX2 might be involved in the regulation of MAPK signaling pathways and so on. Moreover, PAX2 was overexpressed in BC tissues, and PAX2 expression was associated with menopause. PAX2 deficiency could inhibit the growth, migration, and invasion of BC cells.Conclusion: This study suggested that PAX2 was up-regulated in BC, which inhibited BC cell growth, migration, and invasion. Thus, PAX2 could be a potential therapeutic target for BC.

For addressing the issues of pesticide residue analysis characterized by the trace levels of target analytes and the complexity of sample matrices, a selective extracting material, carbon nanotubes (CNTs)/β-cyclodextrin (β-CD) nanocomposite reinforced hollow fiber (HF), was developed. CNTs were chemically modified with β-CD and then the resultant nanocomposite was immobilized into the wall pores and lumen of HF by sol-gel technology. The reinforced HF was applied to direct-immersion mode of solid phase microextraction for the determination of carbaryl and 1-naphthol in tomatoes, coupled with high performance liquid chromatography. The proposed method provided 240- and 215-fold enrichment factors, good linearity in the range of 0.6 to 600 ng/g and 0.2 to 600 ng/g, good repeatability with RSDs of 4.5% and 6.9%, and batch-to-batch reproducibility with RSDs of 7.4% and 8.3% for 1-naphthol and carbaryl, respectively. Moreover, the low limits of detection at 0.05 and 0.15 ng/g for 1-naphthol and carbaryl, respectively, along with the high recovery in the range of 84.2% to 108.9% were obtained. The results showed that the material combined the respective advantages of CNTs, β-CD, and HF, thus, exhibiting efficient adsorption property, outstanding molecular recognition performance, and excellent sample clean-up effect, and it is applicable for pesticide residue analysis in complex matrices. PRACTICAL APPLICATION: The developed extracting material can be used for pesticide residue analysis of tomatoes. Pesticides, carbaryl, and 1-naphthol were detected in tomatoes, the most popular vegetable grown and consumed globally. The results supported the necessity to monitor pesticide residue for public health.

Ferroptosis is a newly form of regulated cell death, which has attracted great attention for tumor therapy. Herein, we prepared nanoscale coordination polymer Fe-NQA particles to deliver iron and NQA (vitamin K3 derivative) into tumor cells, which synergistically promoted ferroptotic therapy for inhibiting tumor growth, preventing metastasis, and overcoming radioresistance.

Doxorubicin (DOX) liposome is a widely used nano-medicine for colorectal cancer treatment. However, doxorubicin therapy increases the level of reactive oxygen species (ROS) in tumor cells, such as hydrogen peroxide (H2O2), which can stabilize hypoxia-inducible-factor-1α (HIF-1α). In a tumor hypoxic microenvironment, HIF-1 can up-regulate tumor-resistance related proteins, including P-glycoprotein (P-gp), glucose transporter 1 (GLUT-1), and matrix metalloproteinase 9 (MMP-9), leading to tumor tolerance to chemotherapy. The functional inhibition of HIF-1 can overcome this resistance and enhance the efficacy of tumor therapy. Here, we encapsulated one of the most effective HIF-1 inhibitors, acriflavine (ACF), and DOX in liposomes (DOX-ACF@Lipo) to construct bifunctional liposomes. ACF and DOX, released from DOX-ACF@Lipo, could effectively suppress the function of HIF-1 and the process of DNA replication, respectively. Consequently, the bifunctional liposome has great potential to be applied in clinics to overcome chemotherapy resistance induced by hypoxia.

Aiming at the problems of low control precision, poor anti-interference ability and poor stability of traditional PID controller, the improvement effect of fuzzy control and BP neural network in closed-loop control of PMSM is compared. In the case of variable speed and variable load, the stability, real-time, anti disturbance and robustness of PMSM system with traditional PID controller, fuzzy self-tuning PID controller and BP neural network PID controller as speed regulator are simulated and analyzed. The simulation results show that the fuzzy self-tuning PID controller has more advantages in the response speed of the system, and can make the system quickly recover to the initial state in case of sudden change. The BP neural network PID controller can ensure the relative stability of the system is better, and can restrain the sudden fluctuation.

Human epidermal growth factor receptor 2 (HER2) is composed of an extracellular domain (ECD), a lipophilic transmembrane region and an intracellular domain (ICD). The most commonly used method to determine the status of HER2 is immunohistochemistry. However, false‑negative results are sometimes given, which causes some patients to lose the opportunity for anti‑HER2 therapy. We found that calpain‑10 may prohibit HER2‑ECD into peripheral blood resulting in a HER2‑negative result by the immunohistochemical method. We enrolled 289 patients into our experiment to assess the relationship between sHER2‑ECD and calpain‑10. The results showed that there was a positive correlation between sHER2‑ECD and calpain‑10. Moreover, we also investigated the prognostic values of sHER2‑ECD and calpain‑10 in breast cancer patients. According to the follow‑up results, positive sHER2‑ECD and tissue calpain‑10 were indicative of a poor prognosis in breast cancer patients. Subsequently, we further validated the relationship between the two molecules in in vitro experiments. In the in vitro experiments, the level of HER2‑ECD in the culture medium was increased or decreased with a decrease or increase in calpain‑10 by transfection technology, showing an inverse association. The results indicated that sHER2‑ECD and tissue calpain‑10 levels were powerful factors to assess the status of HER2. In combination with tissue HER2 detection, the occurrence of false‑negative HER2 was reduced, providing patients with additional treatment opportunities. In conclusion, sHER2‑ECD and tissue calpain‑10 may be used as new prognostic indices for breast cancer.

Abraxane® (Abx), an FDA approved albumin-bound paclitaxel nano-formulation, is one of the most common chemical drugs for the treatment of metastatic triple-negative breast cancer (mTNBC). However, acquired resistance and metastasis are critical factors that limit the treatment of mTNBC by Abx. In particular, both the tumor hypoxic microenvironment and the increase in hydrogen peroxide (H2O2) levels via paclitaxel stimulation primarily mediate the resistance to chemotherapy, where multiple drug resistance proteins such as P-gp and tumor invasion-related cytokines such as VEGF are continuously activated to pump out chemical drugs and aggravate tumor metastasis, respectively. Therefore, it is of great importance to combine tumor oxygenation with commercial chemical drugs for overcoming the acquired resistance and metastasis. In this study, a facile method was developed to deposit manganese dioxide (MnO2) onto the surface of Abraxane® (Abx) to form MnO2-modified Abx (M-Abx). The modification process did not change the critical characteristics of the parent Abx, which might have great potential for application in clinics for the treatment of mTNBC. Tumor oxygenation mediated by M-Abx specifically occurs within the H2O2-overexpressed tumor microenvironment, and significantly downregulates the content of tumor progression-related proteins, such as HIF-1α, P-gp, and VEGF. Ultimately, M-Abx treatment results in about a 2-fold increase in inhibition efficiency of tumor growth in both primary and metastatic tumors compared with traditional Abx therapy. Therefore, oxygen-rich chemotherapy was realized to efficiently sensitize paclitaxel, relieve acquired resistance and inhibit tumor metastasis.

A number of experimental and computational studies have demonstrated the key roles of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in the tumorigenesis of lung adenocarcinoma (LUAC). However, there remains a requirement for prognostic candidate biomarkers acting as ceRNAs for the prediction of overall survival in patients with LUAC. The main goal of the present study was to identify novel lncRNAs associated with LUAC overall survival and assess their prognostic values. The study analyzed coding RNA and ncRNA expression profiles of patients with LUAC by retrieving existing RNA-sequencing datasets from The Cancer Genome Atlas database, and 2,507 differentially expressed mRNAs, 1,633 lncRNAs and 113 miRNAs were screened from patients with LUAC compared with those of adjacent normal samples (P2). Of these LUAC-specific RNAs, 134 lncRNAs, 21 miRNAs and 34 mRNAs were used to build an lncRNA-mRNA-miRNA ceRNA network, among which 8 lncRNAs and 9 mRNAs were associated with overall survival in patients with LUAC by acting as ceRNAs. Next, an lncRNA-based prognostic signature was constructed by risk scoring approach based on the expression levels of 9 prognosis-associated lncRNAs using Cox's regression analysis. Moreover, the prognostic capacity of the 9-lncRNA signature was independent of known clinical prognostic factors. These results provide novel insight into the potential of lncRNA ceRNAs to be candidate biomarkers associated with LUAC overall survival.

Insufficient T-cell infiltration seriously hinders the efficacy of tumor immunotherapy. Induction of immunogenic cell death (ICD) is a potentially feasible approach to increase T-cell infiltration. Since ionizing radiation can only induce low-level ICD, this study constructs Cu-based nanoscale coordination polymers (Cu-NCPs) with mixed-valence (Cu+ /Cu2+ ), which can simultaneously and independently induce the generation of Cu+ -triggered hydroxyl radicals and Cu2+ -triggered GSH elimination, to synergize with radiation therapy for potent ICD induction. Markedly, this synergetic therapy remarkably enhances dendritic cell maturation and promotes antitumor CD8+ T-cell infiltration, thereby potentiating the development of checkpoint blockade immunotherapies against primary and metastatic tumors.

Hypoxia, and hypoxia inducible factor-1 (HIF-1), can induce tumor resistance to radiation therapy. To overcome hypoxia-induced radiation resistance, recent studies have described nanosystems to improve tumor oxygenation for immobilizing DNA damage and simultaneously initiate oxygen-dependent HIF-1α degradation. However, HIF-1α degradation is incomplete during tumor oxygenation treatment alone. Therefore, tumor oxygenation combined with residual HIF-1 functional inhibition is crucial to optimizing therapeutic outcomes of radiotherapy. Here, a reactive oxygen species (ROS) responsive nanoplatform is reported to successfully add up tumor oxygenation and HIF-1 functional inhibition. This ROS responsive nanoplatform, based on manganese dioxide (MnO2) nanoparticles, delivers the HIF-1 inhibitor acriflavine and other hydrophilic cationic drugs to tumor tissues. After reacting with overexpressed hydrogen peroxide (H2O2) within tumor tissues, Mn2+ and oxygen molecules are released for magnetic resonance imaging and tumor oxygenation, respectively. Cooperating with the HIF-1 functional inhibition, the expression of tumor invasion-related signaling molecules (VEGF, MMP-9) is obviously decreased to reduce the risk of metastasis. Furthermore, the nanoplatform could relieve T-cell exhaustion via downregulation of PD-L1, whose effects are similar to the checkpoint inhibitor PD-L1 antibody, and subsequently activates tumor-specific immune responses against abscopal tumors. These therapeutic benefits including increased X-ray-induced damage, downregulated resistance, and T-cell exhaustion related proteins expression achieved synergistically the optimal inhibition of tumor growth. Overall, this designed ROS responsive nanoplatform is of great potential in the sensitization of radiation for combating primary and metastatic tumors.

Introduction: Metastasis is thought to result from tumour cell entry into the circulation and migration to distant organs, where the mutation landscape of metastatic breast cancer (MBC) may shift and vary. The genotypic features of circulating tumour cells (CTCs) typically differ from those of primary breast cancer (BC) cells. Gene mutation analysis of CTCs in MBC may benefit patients by identifying those amenable to specific therapies. Currently, CTCs are primarily isolated in vitro from small volumes of blood. The aim of this study was to isolate CTCs in vivo using CellCollector and screen for specific gene mutations in cells from different metastasis organ sites and molecular subtypes in MBC patients. Methods: In this study, we used a novel technology, CellCollector, to collect peripheral CTCs. Thirty MBC patients were enrolled, and 17 were analysed with next-generation sequencing (NGS) methods. Clinical characteristics were analysed along with CTC enumeration and detection rates. Whole-genome amplification (WGA) was used to amplify the CTC genomic DNA of 127 genes. Results: We isolated CTCs in vivo from 20 of 30 MBC patients (66.7%), with a median and mean (range) of 2 (0-15) CTCs. In non-cancer patients, no CTCs were detected. We analysed CTC enumeration and the detection rate in different clinical characteristic subgroups. We found that in their corresponding subgroups, patients younger than 45 years old, with brain metastasis, with three or more metastasis organ sites, or with HER2-positive subtypes had the highest CTC medians and means.As far as clinical characteristics were concerned, the number of CTCs seemed correlated with more advanced clinical characteristics. In the one metastasis organ, two metastasis organs and three or more metastasis organs subgroups, the CTC detection rates were 38.5% (5/13), 77.8% (7/9), and 100.0% (8/8), respectively. The CTC detection rate correlated with the number of metastasis organs; patients with more metastasis organ sites had higher CTC detection rates. We also found that different metastasis organs and molecular subtypes contain high-frequency mutation genes, and also contain unique gene mutations. Conclusions: In MBC, CellCollector can be used to collect intact CTCs, from which we can obtain gene mutation information. Different metastasis organs and molecular subtypes may have corresponding unique mutations, which may provide a basis for future gene therapy. CTCs enumeration data and correlations to clinicopathologic characteristicsPatients' characteristics CTCs enumeration RangemedianmeanTotal0-1522Age (years) Citation Format: Geng C, Li S, Yang S, Shi J, Ding Y, Gao W, Cheng M, Sun Y, Xie Y, Sang M. In vivo isolation of circulating tumour cells using CellCollector and detection of gene mutations in different metastasis organ sites in breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-01-18.

Dysregulation of microRNAs (miRNAs) in colorectal cancer provides important opportunities for the development of future miRNA‑based therapies. The present study aimed to assess the role of miRNA‑630 (miR‑630) expression in colorectal cancer. HCT116 human colorectal cancer cells were transfected with miR‑630 inhibitor, mimic or control miRNA, and the effects of miR‑630 dysregulation on cell viability, proliferation and apoptosis were analyzed using MTT and bromodeoxyuridine assays, and an annexin V‑fluorescein isothiocyanate cell apoptosis kit, respectively. In addition, the changes in the protein expression of proliferation‑associated and AKT signaling pathway proteins were analyzed by western blot analysis. The results of the present study demonstrated that overexpression of miR‑630 significantly promoted HCT116 cell proliferation however inhibited apoptosis. Furthermore, miR‑630 overexpression reduced the protein expression of p27, BCL2‑associated X apoptosis regulator, procaspase‑3 and active caspase‑3, and increased the levels of phosphorylated‑AKT and BCL2 apoptosis regulator. The suppression of miR‑630 led to the opposite results. In conclusion, the present findings suggested that miR‑630 may function as an oncogenic miRNA in colorectal cancer, and may promote cellular proliferation and inhibit apoptosis, through the regulation of the expression of p27 and the AKT signaling pathway. The present study suggested that the inhibition of miR‑630 may have potential as an alternative therapeutic strategy for the treatment of patients with colorectal cancer.

The present study aimed to identify specific microRNAs (miRs) and their predicted target genes to clarify the molecular mechanisms of colorectal cancer (CRC). An miR expression profile (array ID, GSE39833), which consisted of 88 CRC samples with various tumor-necrosis-metastasis stages and 11 healthy controls, was downloaded from the Gene Expression Omnibus database. Subsequently, the differentially expressed miRs and their target genes were screened. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways of target genes were analyzed using the Database for Annotation Visualization and Integrated Discovery. A protein-protein interaction (PPI) network of the target genes was constructed using the Search Tool for the Retrieval of Interacting Genes database. The present study identified a total of 18 differentially expressed miRs (upregulated, 8; downregulated, 10) in the sera of the CRC patients compared with the healthy controls. Of these, 3 upregulated (let-7b, miR-1290 and miR-126) and 2 downregulated (miR-16 and miR-760) differentially expressed miRs and their target genes, including cyclin D1 (CCND1), v-myc avian myelocytomatosis viral oncogene homolog (MYC), phosphoinositide-3-kinase, regulatory subunit 2 (beta) (PIK3R2) and SMAD family member 3 (SMAD3), were significantly enriched in the CRC developmental pathway. All these target genes had higher node degrees in the PPI network. In conclusion, let-7b, miR-1290, miR-126, miR-16 and miR-760 and their target genes, CCND1, MYC, PIK3R2 and SMAD3, may be important in the molecular mechanisms for the progression of CRC.