Zinc deficiency increases lung inflammation and fibrosis in obese mice by promoting oxidative stress.

BACKGROUND: Zinc deficiency can lead to multiple organ damage. In this study, we investigated the effects of zinc deficiency on obesity-related lung damage. METHODS: C57BL/6 J mice were fed a diet with differing amounts of zinc and fat over a 6-month period. Palmitic acid was used to stimulate A549 cells to construct a high-fat alveolar epithelial cell model. Western blotting and histopathological staining were performed on animal tissues. Nuclear expression of nuclear factor erythroid 2-related factor 2 (Nrf2) was detected in cultured cells. A reactive oxygen species (ROS) assay kit was used to detect intracellular ROS. Furthermore, Nrf2 siRNA was used to examine zinc deficiency effects on A549 cells. RESULTS: Pathological results showed significant damage to the lung structure of mice in the high-fat and low-zinc diet group, with a significant increase in the expression of inflammatory (IL-6, TNF-α) and fibrosis (TGFß1, PAI-1) factors, combined with a decrease in the expression of Nrf2, HO-1 and NQO1 in the antioxidant pathway. In A549 cells, high fat and low zinc levels aggravated ROS production. Western blot and immunofluorescence results showed that high fat and zinc deficiency inhibited Nrf2 expression. After Nrf2-specific knockout in A549 cells, the protective effect of zinc on oxidant conditions induced by high fat was reduced. Phosphorylated Akt and PI3K levels were downregulated on the high-fat and low-zinc group compared with the high-fat group. CONCLUSIONS: Zinc attenuated lung oxidative damage in obesity-related lung injury and Nrf2 activation is one of the important mechanisms of this effect. GENERAL SIGNIFICANCE: Regulating zinc homeostasis through dietary modifications or supplemental nutritional therapy can contribute to the prevention and treatment of obesity-related lung injury.

A new large area MCP-PMT for high energy detection.

20-inch Large area photomultiplier tube based on microchannel plate (MCP-PMT) is newly developed in China. It is widely used in high energy detection experiments such as Jiangmen Underground Neutrino Observatory (JUNO), China JinPing underground Laboratory (CJPL) and Large High Altitude Air Shower Observatory (LHAASO). To overcome the poor time performance of the existing MCP-PMT, a new design of large area MCP-PMT is proposed in this paper. Three-dimensional models are developed in CST Studio Suite to validate its feasibility. Effects of the size and bias voltage of the focusing electrodes and MCP configuration on the collection efficiency (CE) and time performance are studied in detail using the finite integral technique and Monte Carlo method. Based on the simulation results, the optimized operating and geometry parameters are chosen. Results show that the mean ratio of photoelectrons landing on the MCP active area is 97.5%. The acceptance fraction of the impinging photoelectrons is close to 100% due to the emission of multiple secondary electrons when hitting the MCP top surface. The mean transit time spread (TTS) of the photoelectrons from the photocathode is 1.48 ns.

Prognostic significance of peripheral blood S100A12, S100A8, and S100A9 concentrations in idiopathic pulmonary fibrosis.

BACKGROUND: S100A12, S100A8, and S100A9 are inflammatory disease biomarkers whose functional significance in idiopathic pulmonary fibrosis (IPF) remains unclear. We evaluated the significance of S100A12, S100A8, and S100A9 levels in IPF development and prognosis. METHODS: The dataset was collected from the Gene Expression Omnibus (GEO) database and differentially expressed genes were screened using GEO2R. We conducted a retrospective study of 106 patients with IPF to explore the relationships between different biomarkers and poor outcomes. Pearson's correlation coefficient, Kaplan-Meier, Cox regression, and functional enrichment analyses were used to evaluate relationships between these biomarkers' levels and clinical parameters or prognosis. RESULTS: Serum levels of S100A12, S100A8, and S100A9 were significantly elevated in patients with IPF. The two most significant co-expression genes of S100A12 were S100A8 and S100A9. Patients with levels of S100A12 (median 231.21 ng/mL), S100A9 (median 57.09 ng/mL) or S100A8 (median 52.20 ng/mL), as well as combined elevated S100A12, S100A9, and S100A8 levels, exhibited shorter progression-free survival and overall survival. Serum S100A12 and S100A8, S100A12 and S100A9, S100A9 and S100A8 concentrations also displayed a strong positive correlation (rs2 = 0.4558, rs2 = 0.4558, rs2 = 0.6373; P < 0.001). S100A12 and S100A8/9 concentrations were independent of FVC%, DLCO%, and other clinical parameters (age, laboratory test data, and smoking habit). Finally, in multivariate analysis, the serum levels of S100A12, S100A8, and S100A9 were significant prognostic factors (hazard ratio 1.002, P = 0.032, hazard ratio 1.039, P = 0.001, and hazard ratio 1.048, P = 0.003). CONCLUSIONS: S100A12, S100A8, and S100A9 are promising circulating biomarkers that may aid in determining IPF patient prognosis. Multicenter clinical trials are needed to confirm their clinical value.

Measurement of psychological inflexibility: an examination of the psychometric properties of the AAQ-3 compared to AAQ-II.

Due to the limitations of the existing measurements of experiential avoidance, we would like to check the validity of the improved version of Acceptance and Action Questionnaire-II (AAQ-II), i.e., Acceptance and Action Questionnaire-3 (AAQ-3), in Chinese content. The present study was aim to examine the construct and validity of the Chinese version of AAQ-3 in college students and provide an initial validation of this instrument to promote future cross-cultural examination of the psychological flexibility. Totally 1,572 college students were invited to complete the Chinese AAQ-3 and the related questionnaires at the same time. After one month, 380 participates were assessed with same questionnaires to examine the test-retest reliability. The results indicated a similar one-factor solution in the Chinese AAQ-3 to the original version by exploratory factor analysis, parallel analysis and confirmatory factor analysis. Internal consistency and test-retest reliability were good. According to the testing of the measurement invariance, the one-factor model was acceptable across gender (Man = 875, Girl = 697). Additionally, Chinese AAQ-3 was significantly negatively correlated with positive mental health (life satisfaction, mindful attention awareness), significantly positively correlated with negative emotions (depression, anxiety, stress), and significantly positively correlated with AAQ-II and Brief Experiential Avoidance Questionnaire (BEAQ). Besides, Chinese AAQ-3 was the strongest predictor of depression, anxiety, stress and life satisfaction compared to the AAQ-II and BEAQ. However, according to the exploratory structural equation model, the Chinese AAQ-3 demonstrated excellent discriminate validity from negative emotions. Overall, the AAQ-3 modified the limitations of the existing measurements of experiential avoidance (i.e., AAQ-II and BEAQ) as it showed better convergent validity with positive mental health indicators, better discriminant validity with negative emotions, and higher incremental validity. Therefore, the Chinese AAQ-3 is a valid measurement tool for assessing the level of experiential avoidance or psychological flexibility in Chinese college students.

Anti­PD­1/PD­L1 and anti­CTLA­4 associated checkpoint inhibitor pneumonitis in non­small cell lung cancer: Occurrence, pathogenesis and risk factors (Review).

Immune checkpoint inhibitors (ICIs) play a significant anti­tumor role in the management of non­small cell lung cancer. The most broadly used ICIs are anti­programmed death 1 (PD­1), anti­programmed cell death­ligand 1, and anti­cytotoxic T lymphocyte­associated antigen­4 monoclonal antibody. Compared with traditional chemotherapy, ICIs have the advantages of greater efficiency and more specific targeting. However, the resulting immune­related adverse events limit the clinical application of ICIs, especially checkpoint inhibitor pneumonitis (CIP). CIP chiefly occurs within 6 months of administration of ICIs. Excessive activation and amplification of cytotoxic T lymphocytes, helper T cells, downregulation of regulatory T cells, and over­secretion of pro­inflammatory cytokines are the dominant mechanisms underlying the pathophysiology of CIP. The dysregulation of innate immune cells, such as an increase in inflammatory monocytes, dendritic cells, neutrophils and M1 polarization of macrophages, an increase in IL­10 and IL­35, and a decrease in eosinophils, may underlie CIP. Although contested, several factors may accelerate CIP, such as a history of previous respiratory disease, radiotherapy, chemotherapy, administration of epidermal growth factor receptor tyrosine kinase inhibitors, PD­1 blockers, first­line application of ICIs, and combined immunotherapy. Interestingly, first­line ICIs plus chemotherapy may reduce CIP. Steroid hormones remain the primary treatment strategy against grade ≥2 CIP, although cytokine blockers are promising therapeutic agents. Herein, the current research on CIP occurrence, clinical and radiological characteristics, pathogenesis, risk factors, and management is summarized to further expand our understanding, clarify the prognosis, and guide treatment.

Genomic Fingerprint Associated with Familial Idiopathic Pulmonary Fibrosis: A Review.

Idiopathic pulmonary fibrosis (IPF) is a severe interstitial lung disease; although the recent introduction of two anti-fibrosis drugs, pirfenidone and Nidanib, have resulted in a significant reduction in lung function decline, IPF is still not curable. Approximately 2-20% of patients with IPF have a family history of the disease, which is considered the strongest risk factor for idiopathic interstitial pneumonia. However, the genetic predispositions of familial IPF (f-IPF), a particular type of IPF, remain largely unknown. Genetics affect the susceptibility and progression of f-IPF. Genomic markers are increasingly being recognized for their contribution to disease prognosis and drug therapy outcomes. Existing data suggest that genomics may help identify individuals at risk for f-IPF, accurately classify patients, elucidate key pathways involved in disease pathogenesis, and ultimately develop more effective targeted therapies. Since several genetic variants associated with the disease have been found in f-IPF, this review systematically summarizes the latest progress in the gene spectrum of the f-IPF population and the underlying mechanisms of f-IPF. The genetic susceptibility variation related to the disease phenotype is also illustrated. This review aims to improve the understanding of the IPF pathogenesis and facilitate his early detection.

Psychological mechanism of acceptance and commitment therapy and rational emotive behavior therapy for treating hoarding: Evidence from randomized controlled trials.

Hoarding is a common problem behavior worldwide and is detrimental to the physical and mental health of individuals and groups. Currently, effective interventions for hoarding are cognitive-behavioral therapies, but their post-intervention efficacy is questionable, and the available research does not examine the mediating variables of the effects of interventions on clinical outcomes. Moreover, current research on hoarding has focused on Western countries. Therefore, there is a need to investigate the efficacy of other forms of cognitive behavioral therapy on hoarding as well as other psychological outcomes related to hoarding and mediating variables that contribute to its effectiveness in different cultural contexts. One hundred thirty-nine college students with higher hoarding behaviors were randomly divided into three groups: 45 in the Acceptance and Commitment Therapy (ACT) group, 47 in the Rational Emotive Behavior Therapy (REBT) group, and 47 in the control group. They completed the Saving Inventory-Revised (SI-R), Obsessive-Compulsive Symptom Scale (OCSS), Difficulties in Emotion Regulation Scale (DERS), Experiences in Close Relationships Inventory-Attachment Anxiety Subscale (ECR), Depression Anxiety Stress Scales (DASS-21), Acceptance and Action Questionnaire II (AAQ-II), and Cognitive Fusion Questionnaire (CFQ) before and immediately after the intervention. The results showed that ACT and REBT improved individuals' psychological flexibility, cognitive fusion, acquisition-difficulty discarding, clutter, negative affect (anxiety, depression, stress), attachment anxiety, obsessive-compulsive disorder, and difficulty in emotion regulation compared to the control group. In addition, ACT was more effective than REBT in improving psychological flexibility and reducing hoarding, cognitive fusion, depression, stress, and obsessive-compulsive disorder; there were no significant differences between the two in anxiety and emotion regulation difficulties. Furthermore, psychological flexibility is a mediator of the effect of ACT and REBT on some behavioral and psychological outcomes (hoarding, negative affect, attachment anxiety). Limitations were discussed.

Protective role of zinc in the pathogenesis of respiratory diseases.

Respiratory diseases remain a major cause of morbidity and mortality worldwide. An imbalance of zinc, an essential trace element, is associated with a variety of lung diseases. We reviewed and summarized recent research (human subjects, animal studies, in vitro studies) on zinc in respiratory diseases to explore the protective mechanism of zinc from the perspective of regulation of oxidative stress, inflammation, lipid metabolism, and apoptosis. In the lungs, zinc has anti-inflammatory, antioxidant, and antiviral effects; can inhibit cancer cell migration; can regulate lipid metabolism and immune cells; and exerts other protective effects. Our comprehensive evaluation highlights the clinical and experimental effects of zinc in the pathogenesis of respiratory diseases. Our analysis also provides insight into the clinical application of zinc-targeted therapy for respiratory diseases.

Which outcome variables are associated with psychological inflexibility/flexibility for chronic pain patients? A three level meta-analysis.

The psychological flexibility model can be seen as a basis for an integrated and progressive psychological approach to chronic pain management. Some researchers suggest that psychological flexibility and inflexibility represent distinct processes and constructs. This meta-analysis is the first to provide a summary estimate of the overall effect size for the relationship between psychological (in)flexibility and common outcomes among chronic pain patients. The research protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO, https://www.crd.york.ac.uk/PROSPERO/), registration number CRD42021285705. Four databases were searched (PsycINFO; PubMed; Web of Science, CINAHL) along with reference lists. Thirty-six cross-sectional studies were included (7,779 participants). Meta-analyses (random effects model) indicated a significant medium negative association between psychological flexibility and pain intensity or functional impairment. The present study also indicated a significant small to medium association between psychological inflexibility and pain intensity, a nearly large association between psychological inflexibility and functional impairment as well as the quality of life, and a large association between psychological inflexibility and anxiety/depression. Due to the limited number of included studies, the relationship between risk behavior and psychological inflexibility may not be significant. Types of countries and instruments measuring psychological inflexibility may explain part of the heterogeneity. These findings may carry significant implications for chronic pain patients regarding the potential relationship between psychological inflexibility or flexibility and these outcomes. It may consequently form the basis for more robust testing of causal and manipulable relationships. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021285705.

Cognitive Defusion and Psychological Flexibility Predict Negative Body Image in the Chinese College Students: Evidence from Acceptance and Commitment Therapy.

Body dissatisfaction is a global phenomenon. Despite the significant cultural difference, most research on negative body image was conducted in Western countries. How do cognitive fusion and psychological flexibility relate to negative body image in the Chinese population? In the present study, this question was investigated through the intervention technique, Acceptance and Commitment Therapy (ACT). Here, 86 young Chinese university students with high negative physical self were invited, in which 42 students received 10 sessions of group-based ACT intervention in a clinical setting while the remained acted as the control group with no intervention. Pretests showed no statistical differences in negative body image between these two groups, while both cognitive fusion and psychological flexibility predicted negative body image. Post-pre tests showed no change in the control group, while enhanced cognitive defusion and psychological flexibility in the ACT group. Individual differences in psychological flexibility and cognitive defusion enhancement predicted improved body image. A strong association of implicit body image with Fatness and Shortness changes suggested that although with individual differences, those components could be internalized during the intervention in the College students.

The protective effect of natural medicines against excessive inflammation and oxidative stress in acute lung injury by regulating the Nrf2 signaling pathway.

Acute lung injury (ALI) is a common critical disease of the respiratory system that progresses into acute respiratory distress syndrome (ARDS), with high mortality, mainly related to pulmonary oxidative stress imbalance and severe inflammation. However, there are no clear and effective treatment strategies at present. Nuclear factor erythroid 2-related factor 2(Nrf2) is a transcription factor that interacts with multiple signaling pathways and regulates the activity of multiple oxidases (NOX, NOS, XO, CYP) related to inflammation and apoptosis, and exhibits antioxidant and anti-inflammatory roles in ALI. Recently, several studies have reported that the active ingredients of natural medicines show protective effects on ALI via the Nrf2 signaling pathway. In addition, they are cheap, naturally available, and possess minimal toxicity, thereby having good clinical research and application value. Herein, we summarized various studies on the protective effects of natural pharmaceutical components such as polyphenols, flavonoids, terpenoids, alkaloids, and polysaccharides on ALI through the Nrf2 signaling pathway and demonstrated existing gaps as well as future perspectives.

High-frequency repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex reduces drug craving and improves decision-making ability in methamphetamine use disorder.

Methamphetamine abuse is escalating worldwide. Its strong and irreversible neurotoxicity generally causes structural and functional changes in the brain. Repetitive transcranial magnetic stimulation (rTMS) as a non-invasive tool can be used to modulate neuronal activity, cortical excitability, and dopaminergic neurotransmission. This study aims to explore the efficacy of high-frequency rTMS in reducing drug craving and increasing decision-making ability for methamphetamine use disorder patients. Sixty-four methamphetamine use disorder patients were randomized to sham rTMS group and 10-Hz rTMS group. Visual analog scale (VAS) and Iowa game test (IGT) were used to evaluate drug craving and cognitive decision-making ability before and after treatment. Before the treatment, the two groups had no differences in the scores of VAS and IGT. After the intervention, VAS scores of 10-Hz rTMS group were significantly lower than that of sham rTMS group. In addition, the two groups had significant differences in the net score of IGT on block 4 and block 5, which favoured the 10-Hz rTMS group. Taken together, the present results suggest that High-frequency rTMS can be used to reduce drug craving and improve decision-making function for methamphetamine use disorder.

Tensile Property and Corrosion Performance of Ag Microalloying of Al-Cu Alloys for Positive Electrode Current Collectors of Li-Ion Batteries.

The development of a current collector for Li-ion batteries is of great significance for improving the performance of Li-ion batteries. Tensile property and corrosion performance of the positive electrode current collectors are an indispensable prerequisite for the realization of high-performance Li-ion batteries. In our study, the effects of Ag alloying on the microscopic structure, electrical conductivity, tensile property and corrosion resistance of Al-xCu (x = 0.1-0.15%) alloy foils were investigated. Moderate Ag addition on the Al-Cu alloy could reduce the size of second phases and promote the formation of second phases. The tensile strength of the Al-0.1Cu-0.1Ag alloy was higher than that of the Al-0.1Cu alloy at both room and high temperatures. All of the alloy foils demonstrated high electrical conductivity around 58% ICAS. The corrosion potential and corrosion current density of the Al-0.1Cu alloy were demonstrated by Tafel polarization to be -873 mV and 37.12 µA/cm2, respectively. However, the Al-0.1Cu-0.1Ag alloy showed enhanced corrosion resistance after the Ag element was added to the Al-0.1Cu alloy, and the Al-0.1Cu-0.1Ag alloy had a greater positive corrosion potential of -721 mV and a lower corrosion current density of 1.52 µA/cm2, which suggests that the Ag element could significantly improve the corrosion resistance of the Al-Cu alloy.

Associations Between Six Core Processes of Psychological Flexibility and Functioning for Chronic Pain Patients: A Three-Level Meta-Analysis.

The previous research showed contradictions in the relationships between psychological flexibility processes and functioning. This meta-analysis is the first to provide a comprehensive meta-analysis of the associations between six core processes of psychological flexibility and functioning among chronic pain patients. Four databases were searched (PsycINFO; PubMed; CINAHL; Web of Science) along with reference lists. Thirty-six cross-sectional studies were included (7,812 chronic pain patients). A three-level meta-analytic model was used to examine the associations. The publication bias was assessed with the Egger test, funnel plot, and p-curve analysis. Significant associations were found between functioning and six processes of psychological flexibility (i.e., acceptance, defusion, present moment, committed action, self as context, and values). Except for the relationship between defusion and functioning, the relationships between the other five psychological flexibility processes and functioning were all moderated by domains of functioning. No moderators were found regarding age, percentage of females, country, or type of instrument used to measure functioning. These findings may carry significant implications for chronic pain patients and clinical workers. It might be more effective to focus on functioning-related psychological flexibility processes rather than all therapy packages if the relationships between functioning and specific processes of psychological flexibility were better informed. Limitations were also discussed.

Machine learning-based prediction of survival prognosis in cervical cancer.

BACKGROUND: Accurately forecasting the prognosis could improve cervical cancer management, however, the currently used clinical features are difficult to provide enough information. The aim of this study is to improve forecasting capability by developing a miRNAs-based machine learning survival prediction model. RESULTS: The expression characteristics of miRNAs were chosen as features for model development. The cervical cancer miRNA expression data was obtained from The Cancer Genome Atlas database. Preprocessing, including unquantified data removal, missing value imputation, samples normalization, log transformation, and feature scaling, was performed. In total, 42 survival-related miRNAs were identified by Cox Proportional-Hazards analysis. The patients were optimally clustered into four groups with three different 5-years survival outcome (≥ 90%, ≈ 65%, ≤ 40%) by K-means clustering algorithm base on top 10 survival-related miRNAs. According to the K-means clustering result, a prediction model with high performance was established. The pathways analysis indicated that the miRNAs used play roles involved in the regulation of cancer stem cells. CONCLUSION: A miRNAs-based machine learning cervical cancer survival prediction model was developed that robustly stratifies cervical cancer patients into high survival rate (5-years survival rate ≥ 90%), moderate survival rate (5-years survival rate ≈ 65%), and low survival rate (5-years survival rate ≤ 40%).

SOX4 maintains the stemness of cancer cells via transcriptionally enhancing HDAC1 revealed by comparative proteomics study.

BACKGROUND: Cancer stem cells (CSCs) are the root of human cancer development and the major cause of treatment failure. Aberrant elevation of SOX4, a member of SOX (SRY-related HMG-box) family transcription factors, has been identified in many types of human cancer and promotes cancer development. However, the role of SOX4 in CSCs, especially at a proteome-wide level, has remained elusive. The aim of this study is to investigate the effect of SOX4 on the stemness of CSCs and reveal the underlying mechanisms by identification of SOX4-induced proteome changes through proteomics study. RESULTS: Overexpression of SOX4 promotes sphere formation and self-renewal of colorectal cancer cells in vitro and in vivo and elevates the expression levels of CSCs markers. Through iTRAQ-based quantitative proteomics analysis, 215 differentially expressed proteins (128 upregulated, 87 downregulated) in SOX4-overexpressing HCT-116 spheres were identified. The bioinformatic analysis highlighted the importance of HDAC1 as the fundamental roles of its impacted pathways in stem cell maintenance, including Wnt, Notch, cell cycle, and transcriptional misregulation in cancer. The mechanistic study showed that SOX4 directly binds to the promoter of HDAC1, promotes HDAC1 transcription, thereby supporting the stemness of colorectal cancer cells. HDAC1 hallmarks colorectal cancer stem cells and depletion of HDAC1 abolished the stimulatory effect of SOX4. Furthermore, SOX4-HDAC1 axis is conserved in multiple types of cancer. CONCLUSIONS: The results of this study reveal SOX4-induced proteome changes in HCT-116 spheres and demonstrates that transcriptional activation of HDAC1 is the primary mechanism underlying SOX4 maintaining CSCs. This finding suggests that HDAC1 is a potential drug target for eradicating SOX4-driven human CSCs.

Ni/Si-Codoped TiO2 Nanostructure Photoanode for Enhanced Photoelectrochemical Water Splitting.

We synthesized Ni/Si-codoped TiO2 nanostructures for photoelectrochemical (PEC) water splitting, by electrochemical anodization of Ti-1Ni-5Si alloy foils in ethylene glycol/glycerol solutions containing a small amount of water. The effects of annealing temperature on PEC properties of Ni/Si-codoped TiO2 photoanode were investigated. We found that the Ni/Si-codoped TiO2 photoanode annealed at 700 °C had an anatase-rutile mixed phase and exhibited the highest photocurrent density of 1.15 mA/cm2 at 0 V (vs. Ag/AgCl), corresponding to a photoconversion efficiency of 0.70%, which was superior to Ni-doped and Si-doped TiO2. This improvement in PEC water splitting could be attributed to the extended light absorption, faster charge transfer, possibly lower charge recombination, and longer lifetime.

Anodic Fabrication of Ti-Ni-Si-O Nanostructures on Ti10Ni5Si Alloy.

Ti-Ni-Si-O nanostructures were synthesized on Ti10Ni5Si alloy through an electrochemical anodization in electrolyte solutions containing ammonium fluoride (NH4F). The anodic oxide structures were affected by the electrochemical anodization parameters, including the electrolyte viscosity, water content, anodization potential and anodization time. Using an anodization potential of 40 V for 90 min in an ethylene glycol/glycerol electrolyte with 3 vol.% deionized water, highly ordered self-organized nanotube arrays were obtained in the α-Ti phase region of the alloy substrate, with an average inner diameter of 70 nm and a wall thickness of about 12 nm. Self-organized nanopore structures with an average pore diameter of 25 nm grew in the Ti5Si3 phase region. Only etching pits were found in the Ti2Ni phase region. The Ti-Ni-Si-O nanostructures were characterized using scanning electron microscopy and energy dispersive spectroscopy. In addition, a formation mechanism of different nanostructures was presented.

miR-520b Promotes Breast Cancer Stemness Through Hippo/YAP Signaling Pathway.

INTRODUCTION: The breast cancer stem cells contribute to the initiation, progression, recurrence, metastasis as well as resistance of breast cancer. However, the mechanisms underlying the maintenance of breast cancer stemness have not been fully understood. MATERIALS AND METHODS: TCGA and GEO data were used for measuring miR-520b expression in breast cancer tissues. Kaplan-meier analysis was used for determining the relationship between miR-520b expression level and the prognosis of patients. Genetic manipulation was performed by lentivirus system and miR-520b inhibitor was used for knockdown of miR-520b. qRT-PCR and Western blot were employed to determine the mRNA and protein levels, respectively. The stemness and EMT (Epithelial to mesenchymal transition) were assessed by sphere-formation and transwell assay as well as the expression of the related markers. The target genes of miR-520b were identified using the online database starBase V3.0. RESULTS: miR-520b is upregulated in cancer tissues of breast cancer patients and predicts poor prognosis. Upregulation of miR-520b was found in breast cancer stem cells. Ectopic expression of miR-520b promotes the stemness of the breast cancer cells, conversely, depletion of miR-520b attenuates the stemness of these cells. miR-520b positively regulates Hippo/YAP signaling pathway and overexpression of LAST2 abolished the effect of miR-520b on the stemness of breast cancer cells. CONCLUSION: miR-520b promotes the stemness of breast cancer patients by activating Hippo/YAP signaling via targeting LATS2.