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Many evidences show that exosomes play an important role in cancer development, invasion and metastasis. This study is based on the need to explore exosomal protein that promote breast cancer metastasis. We found that tyrosine kinase EphA2 was enriched in Triple-negative breast cancer -derived exosomes and it could disrupt the endothelial monolayer barrier through downregulating tight junction proteins of endothelial cells. These mechanisms were confirmed by in vivo experiments. After periodical injection of exosomal EphA2 into mice caudal vein, we found increased vascular permeability and breast cancer metastases in distant organs, and this phenomenon decreased dramatically after exosomal EphA2 knockdown. This study provides a new mechanism of exosome promoting breast cancer metastasis and suggests a new therapeutic target for the prevention and treatment of breast cancer metastasis.

Conventional therapies for malignant tumors have limitations and disadvantages. In recent years, the cancer starvation therapy has emerged which intends to deprive cancer cells of nutritional supply. There are several approaches to"starve" cancer cells: to intervene tumor angiogenesis by targeted inhibition of angiogenic factors or their receptors and integrins; to block the blood supply of cancer cells by embolizing or compressing blood vessels; to intervene metabolic process of cancer cells by inhibition of the signal pathways of mitochondrial serine-glycine-one earbon metabolism, glycolysis and amino acid metabolism; cancer starvation therapy can be employed with oxidation therapy, chemotherapy, sonodynamic therapy, anti-autophagy therapy or other therapies to achieve synergistic effects. This article reviews the research progress of cancer starvation therapy in recent years and discusses the existing problems.

This study is aimed at screening genes for predicting the sensitivity response and favorable outcome of neoadjuvant therapy in breast cancer. We downloaded neoadjuvant therapy genetic data of breast cancer and separated it into the pathological complete response (pCR) group and the non-pCR group. Differential expression analysis was performed to select the differentially expressed genes (DEGs). After that, we investigated the enriched biological processes and pathways of DEGs. Then, core up/down protein-protein interaction (PPI) network was, respectively, constructed to identify the hub genes. A transcription factor-target gene regulation network was built to screen core transcription factors (TFs). We found one upregulated DEG (KLHDC7B) and four downregulated DEGs (TFF1, LOC440335, SLC39A6, and MLPH) overlapped in three datasets. All DEGs were mainly enriched in pathways related to DNA biosynthesis, cell cycle, immune response, metabolism, and angiogenesis. The hub genes were KRT18, IL7R, HIST1H1A, and E2F1. The core TFs were HOXA9, SPDEF, FOXA1, E2F1, and PGR. RT-qPCR suggested that E2F1 was overexpressed in MCF-7, but HOXA9 was low-expressed. Western blot suggested that the MAPK signal pathway was inhibited in MCF-7/ADR. That is to say, some genes and core TFs can predict the sensitivity response of neoadjuvant therapy in breast cancer. And E2F1 may be involved in the process of drug resistance by regulating the MAPK signaling pathway. These might be useful as sensitive genes for the efficacy evaluation of neoadjuvant chemotherapy in breast cancer.

The oriental armyworm, Mythimna separata, is known for its long-distance seasonal migration and environment-dependent phase polymorphisms. Here, we present a chromosome-level genome reference and integrate multi-omics, functional genetics, and behavioral assays to explore the genetic bases of the hallmark traits of M. separata migration. Gene family comparisons show expansion of gustatory receptor genes in this cereal crop pest. Functional investigation of magnetoreception-related genes and associated flight behaviors suggest that M. separata may use the geomagnetic field to guide orientation in its nocturnal flight. Comparative transcriptome characterizes a suite of genes that may confer the observed plasticity between phases, including genes involved in protein processing, hormone regulation, and dopamine metabolism. We further report molecular signatures that underlie the dynamic regulation of a migratory syndrome coordinating reproduction and flight. Our study yields insights into environment-dependent developmental plasticity in moths and advances our understanding of long-distance migration in nocturnal insect pests.

BACKGROUND No reports of the potential areas of surgeons' aesthetics in blepharoplasty. AIMS To explore the association between the surgeons' own double eyelid morphology and their aesthetics and surgical outcome. METHODS An investigation of 1605 patients was carried collecting the data of double eyelid shape, based on which to propose a preliminary double eyelid classification for analyzing the aesthetics of surgeons. Ten double eyelid surgical cases were randomly collected from each surgeon according to the inclusion criteria, whose double eyelid shape, ideal shape, the selection tendency of surgical approach, most cared factor during surgery, and design concept of eyelid shape were collected. Structural equation modeling (SEM) was performed to assess the association between participants' double eyelid shape, aesthetics, and blepharoplasty outcome. RESULTS Fifty-three double eyelid surgeons were enrolled for study, whose double eyelids shapes mostly were obviously fan-shaped (37.74%) and low-parallel eyelid (26.42%), and the ideal shapes were obviously fan-shaped (41.51%) and high-parallel eyelid (24.53%). 54.72% of the subjects preferred to use the full-incisional method. 45.28% cared for long-term outcome most. Regarding blepharoplasty outcome style, 49.06% of the subjects preferred obviously fan-shaped type and 24.53% for high-parallel type. SEM showed that aesthetics rank increased by 0.692 points for surgeons' shape (P

The main contradiction of the society is changing, the new era calls for high-quality development, and the connotation construction of universities is becoming more and more important. The key point lies in "quality improvement". To realize the leap from "quantity" to "quality" of employment service work, it is necessary to actively change the concept, explore new ways, and expand the service function. From the marxism about the human essence theory and need theory, to respect the principal position of students in education, based on students, social relations and demand systematic construction of "four dimensions of eight framework" employment system, on the basis of graduation to differentiate between joint training, enter oneself for an examination the graduate student, enter oneself for an examination office jobs, entrepreneurship, employment in five modules, from students’ characteristics, the guidance services strategy two dimensions make accurate working mode.

The style of study is the embodiment of the school's academic spirit, attitude and principle, the style of being a man and the embodiment of the school's temperament and soul. Grasp the essence of the style of study, avoid the misunderstanding of the construction of the style of study, based on the practice of the school in which the author is located, and build a systematic style of study construction system in eight aspects, such as guarantee, guidance, support, supervision, cooperation, support, guidance service and value orientation, so as to accomplish the fundamental task of building people by virtue in colleges and universities.

Papillary thyroid cancer (PTC) is the most common type of thyroid malignancy, and it is often observed to overexpress epidermal growth factor receptor (EGFR). Previous research has indicated that EH domain-containing 1 (EHD1) is associated with EGFR-mediated endocytotic recycling in multiple tumor types. The objective of the present study was to determine the protein expression levels and clinical significance of EHD1, EGFR, caveolin-1 (CAV-1) and RAB11 family interacting protein 3 (RAB11FIP3) in PTC. PTC specimens were analyzed for EHD1, EGFR, CAV-1 and RAB11FIP3 expression via immunohistochemistry and western blotting. The associations between protein expression and clinicopathological features were assessed. EHD1, EGFR, CAV-1 and RAB11FIP3 expression levels were increased in human PTC. Additionally, the expression level of EHD1 protein was significantly associated with tumor size, lymph node metastasis and EGFR expression (P

// Yuhui Wang 1, * , Nan Wu 1, * , Bo Pang 1, * , Dandan Tong 2 , Donglin Sun 1 , Haiming Sun 1 , Chunyu Zhang 1 , Wenjing Sun 1 , Xiangning Meng 1 , Jing Bai 1 , Feng Chen 1 , Jingshu Geng 3 , Songbin Fu 1, 4 and Yan Jin 1, 4 1 Laboratory of Medical Genetics, Harbin Medical University, Harbin, China 2 Department of Pathology, Harbin Medical University, Harbin, China 3 Department of Pathology, Third Affiliated Clinical Hospital, Harbin Medical University, Harbin, China 4 Key Laboratory of Medical Genetics, Harbin Medical University, Heilongjiang Higher Education Institutions, Harbin, China * These authors have contributed equally to this work Correspondence to: Yan Jin, email: jinyan@ems.hrbmu.edu.cn Songbin Fu, email: fusb@ems.hrbmu.edu.cn , fusongbin@yahoo.com Keywords: TRIB1, colorectal carcinoma, migration, invasion, MMP-2 Received: November 30, 2016 Accepted: May 01, 2017 Published: May 25, 2017 ABSTRACT Colorectal cancer (CRC) is the third most common cancer in the world and distant metastasis is the leading cause of death among CRC patients. However, the underlying mechanisms of distant metastasis remain largely unknown. Amplification of 8q24 is a common chromosomal abnormality in CRC. In the present study, a putative oncogene at 8q24, TRIB1, was characterized for its role in CRC metastasis and underlying molecular mechanisms. Higher expression of TRIB1 protein was detected in 58/83 (69.9%) of CRC tissues, compared with adjacent non-tumor tissues. Moreover, the expression of TRIB1 was significantly associated with distant metastasis ( P =0.043) and advanced staging ( P =0.008) in CRC tissues. TRIB1 overexpression was also correlated with poor prognosis in CRC patients as analyzed in PrognoScan database. In addition, elevated expression of TRIB1 promoted CRC cell motility and adhesive ability, while silencing of TRIB1 reduced those effects. Further study revealed that TRIB1-mediated migration and invasion of CRC cells required up-regulation of MMP-2 through the activation of FAK/Src and ERK pathway. Collectively, the results suggest that TRIB1 promotes CRC cell motility by activation MMP-2 via the FAK/Src and ERK pathways. It may provide a potential diagnostic and therapeutic target for CRC.

Fungal burden throughout the world is very high and it keeps escalating due to increasing numbers of immunocompromised individuals. In contrast, the drugs used in management of fungal infections are so few some with high toxicity. Furthermore, highly resistant fungal pathogens are emerging for example Candida auris, Candida glabrata, Candida gullemondii and Aspergillus species among others. Thus now, more than ever, there is a need for combined efforts and an all round search for possible solutions to curb these problems. Therefore, the role of probiotics in management of fungal infections is indispensable. In fact, the antimicrobial activity of probiotics has been screened with promising results against microbial pathogens. Although, recent reports indicated that probiotics may also contribute to protect against fungal infections, the research done in checking antifungal activity of probiotics has used varied technology. This calls for harmonization of the methods used to screen and confirm the antimicrobial activity of probiotics and other candidate microorganisms. We therefore sought to address issues of disparity in probiotic research and their outcomes. Thus this paper is in order as it comprehensively reviews' publications, provides a summary of the methods and future prospects of probiotics as antifungal agents.

One common strategy to cope with the difficulties of daily life is suppression. Habitual users of suppression tend to suppress their feelings rather than expressing them. Although this strategy may reduce outward response to emotion, it is not thought to lessen induced negative affect. Moreover, it remains unclear whether people with high suppression scores can reduce negative affect through cognitive reappraisal. In the present study, twenty-nine healthy participants differing in suppression scores were directed to reappraise aversive stimuli during functional magnetic resonance imaging (fMRI). Results showed that higher suppression scores correlated with decreased response of dorsomedial prefrontal cortex (dmPFC) during cognitive reappraisal. Further, high suppression scores related to enhanced negative affect to stimuli with greater negative affect correlating with decreased dmPFC response during cognitive reappraisal. This study suggests that people with high suppression scores experience difficulty in reducing negative affect through cognitive reappraisal and implicates neurobiological processes that may underlie this difficulty.

Zeigarnik effect means that participants tend to recall the unfinished/unsolved tasks more frequently than the finished/solved ones during a subsequent memory task. To get a comprehensive understanding of the relationship between Zeigarnik effect and insightful problem solving, we need to adopt more research methods to explore the brain mechanisms of Zeigarnik effect. People typically go through a period of mental impasses and then are inspired by some heuristic knowledge in real-life scientific problem solving. For example, Newton obtained insights into the law of universal gravitation after observing a ripe apple dropping from the tree which he was sitting under. Based on this, Zhang Qinglin proposed that heuristic strategy is one of the usual strategies in problem solving. Based on the "prototype elicitation" theory, The present study selected 20 scientific inventions-creations problems as the material and adopted the "10 vs 10 learning and testing" as well as "testing-recalling" experimental paradigm. Besides, using voxel-based morphometry (VBM) and the score of "testing-recalling", we investigated the correlation between the zagarnik effect and regional grey matter volume (rGMV) in healthy subjects. The result showed that the Zeigarnik effect was to be positively correlated with rGMV in the bilateral Hippocampus and Parahippocampus. Based on these results above, we can speculated that bigger hippocampus and parahippocampal allow people to maintain target seeking as well as better tolerate ambiguity stimulation.

Phubbing, or the act of snubbing someone in a face-to-face interaction by using a smartphone, is a ubiquitous phenomenon in the digital era. A person being phubbed can feel neglected and has an increased risk of mental illness. The present study examined how being phubbed is related to depression, mediated through self-esteem. Furthermore, this study examined the moderating effect of dispositional forgiveness on the relationship between being phubbed and depression via self-esteem. It was predicted that self-esteem would mediate the relationship between being phubbed and depression, and that this mediating effect would be stronger for individuals with low forgiveness dispositions than for individuals with high forgiveness dispositions. We recruited 995 undergraduates aged 18–20 years from three different universities in China to participate in the current study. Participants completed measures of being phubbed, self-esteem, depression, and dispositional forgiveness. The results revealed that self-esteem mediated the relationship between being phubbed and depression. Additionally, dispositional forgiveness moderated the indirect effect of being phubbed on depression through self-esteem. Unlike what was predicted, the indirect effect of being phubbed on depression was stronger for high forgiveness individuals than for low forgiveness individuals. This unanticipated orientation and other results are discussed.

Many scientific inventions (SI) throughout history were inspired by heuristic prototypes (HPs). For instance, an event or piece of knowledge similar to displaced water from a tub inspired Archimedes' principle. However, the neural mechanisms underlying this insightful problem solving are not very clear. Thus, the present study explored the neural correlates used to solve SI problems facilitated by HPs. Each HP had two versions: a literal description with an illustration (LDI) and a literal description with no illustration (LDNI). Thirty-two participants were divided randomly into these two groups. Blood oxygenation level-dependent fMRI contrasts between LDI and LDNI groups were measured. Greater activity in the right middle occipital gyrus (RMOG, BA19), right precentral gyrus (RPCG, BA4), and left middle frontal gyrus (LMFG, BA46) were found within the LDI group as compared to the LDNI group. We discuss these results in terms cognitive functions within these regions related to problem solving and memory retrieval. (C) 2015 Elsevier Inc. All rights reserved.

In this study, an activation likelihood estimation (ALE) meta-analysis was used to conduct a quantitative investigation of neuroimaging studies on divergent thinking. Based on the ALE results, the functional magnetic resonance imaging (fMRI) studies showed that distributed brain regions were more active under divergent thinking tasks (DTTs) than those under control tasks, but a large portion of the brain regions were deactivated. The ALE results indicated that the brain networks of the creative idea generation in DTTs may be composed of the lateral prefrontal cortex, posterior parietal cortex (such as the inferior pari- etal lobule (BA 40) and precuneus (BA 7)), anterior cingulate cortex (ACC) (BA 32), and several regions in the temporal cortex (such as the left middle temporal gyrus (BA 39), and left fusiform gyrus (BA 37)). The left dorsolateral prefrontal cortex (BA 46) was related to selecting the loosely and remotely associated con- cepts and organizing them into creative ideas, whereas the ACC (BA 32) was related to observing and form- ing distant semantic associations in performing DTTs. The posterior parietal cortex may be involved in the semantic information related to the retrieval and buffering of the formed creative ideas, and several regions in the temporal cortex may be related to the stored long-term memory. In addition, the ALE results of the structural studies showed that divergent thinking was related to the dopaminergic system (e.g., left caudate and claustrum). Based on the ALE results, both fMRI and structural MRI studies could uncover the neural basis of divergent thinking from different aspects (e.g., specific cognitive processing and stable individual difference of cognitive capability). Hum Brain Mapp 00:000-000, 2015. V C 2015 Wiley Periodicals, Inc.

The concept of tolerance of ambiguity (AT) is defined as the way in which an individual tends to perceive and deal with confusing, vague, and unclear situations. AT is generally considered as an important personality trait, but the neural mechanisms underlying individual differences in AT have never been investigated. Using voxel-based morphometry and MSTAT-II scale, we investigated the correlations between AT and regional white matter volume (rWMV) and regional gray matter volume (rGMV) in 351 young healthy subjects. We found AT to be positively correlated with rGMV in the dorsolateral prefrontal cortex (DLPFC), and negatively correlated with rGMV in the precuneus. These results indicate that increased rGMV in the left DLPFC may lead to characteristics of ambiguous stimuli consideration from multiple contexts and risk taking. Decreased rGMV in the left precuneus may be associated with a high tolerance for ambiguity, which attributes uncertainty to self-related factors.

Insight can be the first step toward creating a groundbreaking product. The Representation Change (RC) Theory and the Progress Monitoring (PM) Theory and other theories of insight have been verified through numerous studies, but they indeed are not so perfect. We put forward a Prototype Heuristic Theory of insight and explored its cognitive mechanism by this study. Based on this theory, insight would occur as soon as the critical heuristic information contained in prototypes was suddenly obtained to play an orientational role in the process of searching the right problem solution searching space. The process of prototype heuristics consists of two stages: “representations connection” stage and “relationship mapping” stage and the core process was the representations connection. Furthermore, high semantic similarity between required-function of problems and feature-function of prototypes was the prime condition for representations connection. We also developed the RC Theory and PM Theory in some extent based on our Prototype Heuristic Theory.

Nucleotide binding protein-like, NUBPL, is an assembly factor for human mitochondrial complex I, which is the biggest member of the mitochondrial respiratory chain. However, the relationship between NUBPL and carcinoma progression remains unknown. In this study, NUBPL was characterized for its role in colorectal cancer (CRC) and the underlying molecular mechanisms. Data (n = 197) from the Oncomine database revealed that mRNA levels of NUBPL were remarkably overexpressed in CRC tissues compared with normal tissues. In addition, immunohistochemical analysis of 75 pairs of CRC and non-tumor tissues showed that the expression level of NUBPL was significantly higher in CRC tissues, and its expression level was positively associated with lymph node metastasis (P = 0.028) and advanced staging (P = 0.030). Expression of NUBPL in metastatic lymph nodes of CRC patients was also detected by immunohistochemical staining and high expression levels of NUBPL were observed. Overexpression of NUBPL significantly promoted the migration and invasion ability of CRC cell lines SW480 and SW620, whereas knockdown of NUBPL lead to an opposite effect. Our further study found that NUBPL could induce epithelial-mesenchymal transition (EMT), characterized by downregulation of epithelial markers (E-cadherin) and upregulation of mesenchymal markers (N-cadherin and vimentin). Moreover, NUBPL was able to activate ERK, which is believed to promote EMT and tumor metastasis. Inhibition of ERK suppressed the NUBPL-induced changes in EMT and cell motility. These data showed that NUBPL plays a vital role in CRC migration and invasion by inducing EMT and activating ERK. It might be a novel therapeutic target for CRC.

Previous studies have indicated that caveolin-1 (Cav-1) is able to bind the signal transduction factor epidermal growth factor receptor (EGFR) to regulate its tyrosine kinase activity. The aim of the present study was to evaluate the clinical significance of Cav-1 gene expression in association with the expression of EGFR in patients with breast cancer. Primary breast cancer samples from 306 patients were analyzed for Cav-1 and EGFR expression using immunohistochemistry, and clinical significance was assessed using multivariate Cox regression analysis, Kaplan-Meier estimator curves and the log-rank test. Stromal Cav-1 was downregulated in 38.56% (118/306) of tumor tissues, whereas cytoplasmic EGFR and Cav-1 were overexpressed in 53.92% (165/306) and 44.12% (135/306) of breast cancer tissues, respectively. EGFR expression was positively associated with cytoplasmic Cav-1 and not associated with stromal Cav-1 expression in breast cancer samples; however, low expression of stromal Cav-1 was negatively associated with cytoplasmic Cav-1 expression in total tumor tissues, and analogous results were identified in the chemotherapy group. Multivariate Cox's proportional hazards model analysis revealed that, for patients in the estrogen receptor (ER)(+) group, the expression of stromal Cav-1 alone was a significant prognostic marker of breast cancer. However, in the chemotherapy, human epidermal growth factor receptor 2 (HER-2)(-), HER-2(+) and ER(-) groups, the use of combined markers was more effective prognostic marker. Stromal Cav-1 has a tumor suppressor function, and the combined marker stromal Cav-1/EGFR expression was identified as an improved prognostic marker in the diagnosis of breast cancer. Parenchymal expression of Cav-1 is able to promote EGFR signaling in breast cancer, potentially being required for EGFR-mediated initiation of mitosis.

MicroRNAs play an important role in the regulation of cancer migration, invasion and metastasis. Patients with triple-negative breast cancer (TNBC) have a high incidence of early relapse and metastasis; however, the molecular basis for metastasis and recurrence in these individuals remains largely unknown. Herein, we demonstrate that miR-136 is an anti-invasive microRNA in TNBC and suppresses mesenchymal invasion and metastasis. Our results demonstrated that miR-136 was downregulated in TNBC and negative correlated with the WHO grades. However, RASAL2 was identified as a functional target of miR-136, and was overexpressed in TNBC and correlates with pathological grades. Moreover, overexpression of RASAL2 in a breast cancer cell line rescued miR-136-mediated cell migration and invasion. In conclusion, these results indicate that the miR-136/RASAL2/MET axis act as a suppressor of TNBC metastasis.

Double minute chromosomes (DMs) have important implications for cancer progression because oncogenes frequently amplified on them. We previously detected a functionally undefined gene amplified on DMs, Ribosomal L22-like1 (RPL22L1). The relationship between RPL22L1 and cancer progression is unknown. Here, RPL22L1 was characterized for its role in ovarian cancer (OC) metastasis and its underlying mechanism was examined. DNA copy number and mRNA expression of RPL22L1 in OC cells was analyzed using data obtained from The Cancer Genome Atlas and the Gene Expression Omnibus database. An immunohistochemical analysis of clinical OC specimens was performed and the relationships between expression level and clinicopathological factors were evaluated. Additionally, in vivo and in vitro assays were performed to understand the role of RPL22L1 in OC. RPL22L1 expression was higher in OC specimens than in normal tissues, and its expression level was highly positively correlated with invasion and lymph node metastasis (P < 0.05). RPL22L1 over-expression significantly enhanced intraperitoneal xenograft tumor development in nude mice and promoted invasion and migration in vitro. Additionally, RPL22L1 knockdown remarkably inhibited UACC-1598 cells invasion and migration. Further, RPL22L1 over-expression up-regulated the mesenchymal markers vimentin, fibronectin, and α-SMA, reduced expression of the epithelial markers E-cadherin, α-catenin, and β-catenin. RPL22L1 inhibition reduced expression of vimentin and N-cadherin. These results suggest that RPL22L1 induces epithelial-to-mesenchymal transition (EMT). Our data showed that the DMs amplified gene RPL22L1 is critical in maintaining the aggressive phenotype of OC and in triggering cell metastasis by inducing EMT. It could be employed as a novel prognostic marker and/or effective therapeutic target for OC.

Recent research indicates that RBMS3 may act as a tumor suppressor gene (TSG) in nasopharyngeal carcinoma (NPC) and esophageal squamous cell carcinoma (ESCC). It has been reported that RBMS3 directly binds to the promoter region of c-Myc in ESCC and that β-catenin from both whole cell extracts and nuclear fractionation was significantly downregulated in RBMS3-transfected NPC cells compared to control cells. The aim of this study was to evaluate the clinical significance of the RBMS3 gene expression in relation to the expression of Wnt pathway components in patients with lung squamous cell carcinoma (LSCC). RBMS3, c-Myc and cytoplasmic β-catenin were detected in 39.76, 56.63 and 89.16 % of 83 LSCC samples by immunohistochemistry, respectively, in 83 primary LSCC samples. Semiquantitative reverse transcriptase-polymerase chain reaction and Western blotting demonstrated decreased RBMS3 mRNA and expression in 33.33 % (10/30) and 36.67 % (11/30) tumor tissues, respectively. Statistical correlation analysis showed RBMS3 to be negatively correlated with c-Myc (r = −0.384, p < 0.001) and not correlated with cytoplasmic β-catenin in the LSCC samples. Multivariate Cox proportional hazards model analysis showed that the combined marker RBMS3/c-Myc was an independent prognostic indicator of overall survival (p = 0.001; HR 3.470; IC 95 %, 1.652–7.290), and c-Myc was a prognostic indicator of disease-free survival (p < 0.001; HR 3.182; IC 95 %, 1.961–8.920). RBMS3 is a novel TSG in LSCC, and its downregulation facilitates development and progression of LSCC. Therefore, it is suggested that Rbms3 as a tumor marker may play an important role in diagnosis of LSCC.