Cationic Ir(III) Complexes with 4-Fluoro-4'-pyrazolyl-(1,1'-biphenyl)-2-carbonitrile as the Cyclometalating Ligand: Synthesis, Characterizations, and Application to Ultrahigh-Efficiency Light-Emitting Electrochemical Cells.

Light-emitting electrochemical cells (LECs) promise low-cost, large-area luminescence applications with air-stabilized electrodes and a versatile fabrication that enables the use of solution processes. Nevertheless, the commercialization of LECs is still encountering many obstacles, such as low electroluminescence (EL) efficiencies of the ionic materials. In this paper, we propose five blue to yellow ionic Ir complexes possessing 4-fluoro-4'-pyrazolyl-(1,1'-biphenyl)-2-carbonitrile (ppfn) as a novel cyclometalating ligand and use them in LECs. In particular, the device within di[4-fluoro-4'-pyrazolyl-(1,1'-biphenyl)-2-carbonitrile]-4,4'-di-tert-butyl-2,2'-bipyridyl iridium(III) hexafluorophosphate (DTBP) shows a remarkable photoluminescence quantum yield (PLQY) of 70%, and by adjusting the emissive-layer thickness, the maximal external quantum efficiency (EQE) reaches 22.15% at 532 nm under the thickness of 0.51 µm, showing the state-of-the-art value for the reported blue-green LECs.

On-Demand Assembly of Nanocrystals into a Superstructure Library in Co(OH)2 Single-Walled Nanotubes.

The hierarchical self-assembly of colloidal particles facilitates the bottom-up manufacturing of metamaterials with synergistically integrated functionalities. Here, we define a modular assembly methodology that enables multinary co-assembly of nanoparticles in one-dimensional confined space. A series of isotropic and anisotropic nanocrystals such as plasmonic, metallic, visible, and near-infrared responsive nanoparticles as well as transition-metal phosphides can be selectively assembled within the single-walled Co(OH)2 nanotubes to achieve various increasingly sophisticated assembly systems, including unary, binary, ternary, and quaternary superstructures. Moreover, the selective assembly of distinct functional nanoparticles produces different integrated functional superstructures. This generalizable methodology provides predictable pathways to complex architectures with structural programming and customization that are otherwise inaccessible.

Electronic Modulation of Metal-Organic Frameworks Caused by Atomically Dispersed Ru for Efficient Hydrogen Evolution.

Designing excellent electrocatalysts for the hydrogen evolution reaction (HER) is extremely significant in producing clean and sustainable hydrogen fuel. Herein, a rational strategy is developed to fabricate a promising electrocatalyst by introducing atomically dispersed Ru into a cobalt-based metal-organic framework (MOF), Co-BPDC (Co(bpdc)(H2 O)2 , BPDC: 4,4'-Biphenyldicarboxylic acid). The obtained CoRu-BPDC nanosheet arrays exhibit remarkable HER performance with an overpotential of 37 mV at a current density of 10 mA cm-2 in alkaline media, which is superior to most of the MOF-based electrocatalysts and comparable to the commercial Pt/C. Synchrotron radiation-based X-ray absorption fine structure (XAFS) spectroscopy studies verify that the isolated Ru atoms are dispersed in Co-BPDC nanosheets with the formation of five-coordinated Ru-O5 species. XAFS spectroscopy combined with density functional theory (DFT) calculations unravels that atomically dispersed Ru can modulate the electronic structure of the as-obtained Co-BPDC, contributing to the optimization of binding strength for H* and the enhancement of HER performance. This work opens a new avenue to rationally design highly-active single-atom modified MOF-based HER electrocatalysts via modulating electronic structures of MOF.

White Light-Emitting Electrochemical Cells Employing Phosphor-Sensitized Thermally Activated Delayed Fluorescence to Approach All-Phosphorescent Device Efficiencies.

Solid-state light-emitting electrochemical cells (LECs) show promising advantages of simple device architecture, low operation voltage, and insensitivity to the electrode work functions such that they have high potential in low-cost display and lighting applications. In this work, novel white LECs based on phosphor-sensitized thermally activated delayed fluorescence (TADF) are proposed. The emissive layer of these white LECs is composed of a blue-green phosphorescent host doped with a deep-red TADF guest. Efficient singlet-to-triplet intersystem crossing (ISC) on the phosphorescent host and the subsequent Förster energy transfer from the host triplet excitons to guest singlet excitons can make use of both singlet and triplet excitons on the host. With the good spectral overlap between the host emission and the guest absorption, 0.075 wt.% guest doping is sufficient to cause substantial energy transfer efficiency (ca. 40 %). In addition, such a low guest concentration also reduces the self-quenching effect and a high photoluminescence quantum yield of up to 84 % ensures high device efficiency. The phosphor-sensitized TADF white LECs indeed show a high external quantum efficiency of 9.6 %, which is comparable with all-phosphorescent white LECs. By employing diffusive substrates to extract the light trapped in the substrate, the device efficiency can be further improved by ca. 50 %. In the meantime, the intrinsic EL spectrum and device lifetime of the white LECs recover since the microcavity effect is destroyed. This work successfully demonstrates that the phosphor-sensitized TADF white LECs are potential candidates for efficient white light-emitting devices.

Ultrathin Carbon Nitride Nanosheets Exfoliated and In Situ Modified with a Nickel Bis(Chelate) Complex for Boosting Photocatalytic Performances.

Exfoliation and interfacial modification of two-dimensional (2D) polymeric carbon nitride (CN) are considerably vital for applications in photo/electrocatalysis fields. Here, a grinding-ultrasonic route was designed to construct nickel bis(chelate) complex (Ni(abt)2, abt = 2-aminobenzenethiolate)-modified CN ultrathin nanosheets. Under the assistance of the shear force derived from the grinding process, Ni(abt)2 was implanted into the interlamination of bulk CN, resulting in the formation of ultrathin CN (UCN) nanosheets. Simultaneously, Ni(abt)2 molecules were anchored on the surfaces of as-formed UCN nanosheets due to the π-π stacking interaction. Interestingly, compared with single Ni(abt)2 and UCN, the as-obtained Ni(abt)2/UCN nanosheets exhibited excellent photocatalytic hydrogen evolution capability. A molecule-semiconductor internal electron transmission mechanism was suggested for explaining the separation and transfer of electron-hole pairs. Density functional theory (DFT) calculations demonstrated that the interface-induced electron redistribution tuned the electron density and hydrogen adsorption of the active centers, thus enhancing the photocatalytic performance of the hybrid catalyst. In addition, the as-obtained Ni(abt)2/UCN nanosheets could also catalyze the reduction of nitroaromatics in the presence of NaBH4. It was found that under the simulated sunlight irradiation, the conversion efficiency of nitroaromatic compounds to amino aromatic ones was up to 97.3%, far higher than that under the condition without light irradiation (51.7%), suggesting that the photocatalytic-produced hydrogen took part in the reduction of nitroaromatic compounds.

Urban-rural differences in healthcare utilization among beneficiaries in China's new cooperative medical scheme.

BACKGROUND: The New Cooperative Medical Scheme (NCMS) is a voluntary social health insurance program launched in 2002 for rural Chinese residents where 80% of people were without health insurance of any kind. Over time, several concerns about this program have been raised related to healthcare utilization disparities for NCMS participants in urban versus rural regions. Our study uses 2015 national survey data to evaluate the extent of these urban and rural disparities among NCMS beneficiaries. METHODS: Data for our study are based on the Chinese Health and Retirement Longitudinal Study (CHARLS) for 2015. Our 12,190-patient sample are urban and rural patients insured by NCMS. We use logistic regression analyses to compare the extent of disparities for urban and rural residence of NCMS beneficiaries in (1) whether individuals received any inpatient or outpatient care during 2015 and (2) for those individuals that did receive care, the extent of the variation in the number of inpatient and outpatient visits among each group. RESULTS: Our regression results reveal that for urban and rural NCMS patients in 2015, there were no significant differences in inpatient or outpatient utilization for either of the dependent variables - 1) whether or not the patient had a visit during the last year, or 2) for those that had a visit, the number of visits they had. Patient characteristics: age, sex, employment, health status, chronic conditions, and per capita annual expenditures - all had significant impacts on whether or not there was an inpatient or outpatient visit but less influence on the number of inpatient or outpatient visits. CONCLUSIONS: For both access to inpatient and outpatient facilities and the level of utilization of these facilities, our results reveal that both urban and rural NCMS patients have similar levels of resource utilization. These results from 2015 indicate that utilization angst about urban and rural disparities in NCMS patients do not appear to be a significant concern.

Hybrid White-Light-Emitting Electrochemical Cells Based on a Blue Cationic Iridium(III) Complex and Red Quantum Dots.

Solid-state white light-emitting electrochemical cells (LECs) show promising advantages of simple solution fabrication processes, low operation voltage, and compatibility with air-stable cathode metals, which are required for lighting applications. To date, white LECs based on ionic transition metal complexes (iTMCs) have shown higher device efficiencies than white LECs employing other types of materials. However, lower emission efficiencies of red iTMCs limit further improvement in device performance. As an alternative, efficient red CdZnSeS/ZnS core/shell quantum dots were integrated with a blue iTMC to form a hybrid white LEC in this work. By achieving good carrier balance in an appropriate device architecture, a peak external quantum efficiency and power efficiency of 11.2 % and 15.1 lm W-1, respectively, were reached. Such device efficiency is indeed higher than those of the reported white LECs based on host-guest iTMCs. Time- and voltage-dependent electroluminescence (EL) characteristics of the hybrid white LECs were studied by means of the temporal evolution of the emission-zone position extracted by fitting the simulated and measured EL spectra. The working principle of the hybrid white LECs was clarified, and the high device efficiency makes potential new white-emitting devices suitable for solid-state lighting technology possible.

Resilience to multiple stressors in an aquatic plant and its microbiome.

PREMISE: Outcomes of species interactions, especially mutualisms, are notoriously dependent on environmental context, and environments are changing rapidly. Studies have investigated how mutualisms respond to or ameliorate anthropogenic environmental changes, but most have focused on nutrient pollution or climate change and tested stressors one at a time. Relatively little is known about how mutualisms may be altered by or buffer the effects of multiple chemical contaminants, which differ fundamentally from nutrient or climate stressors and are especially widespread in aquatic habitats. METHODS: We investigated the impacts of two contaminants on interactions between the duckweed Lemna minor and its microbiome. Sodium chloride (salt) and benzotriazole (a corrosion inhibitor) often co-occur in runoff to water bodies where duckweeds reside. We tested three L. minor genotypes with and without the culturable portion of their microbiome across field-realistic gradients of salt (3 levels) and benzotriazole (4 levels) in a fully factorial experiment (24 treatments, tested on each genotype) and measured plant and microbial growth. RESULTS: Stressors had conditional effects. Salt decreased both plant and microbial growth and decreased plant survival more as benzotriazole concentrations increased. In contrast, benzotriazole did not affect microbial abundance and even benefited plants when salt and microbes were absent, perhaps due to biotransformation into growth-promoting compounds. Microbes did not ameliorate duckweed stressors; microbial inoculation increased plant growth, but not at high salt concentrations. CONCLUSIONS: Our results suggest that multiple stressors matter when predicting responses of mutualisms to global change and that beneficial microbes may not always buffer hosts against stress.

[A new antiviral isoquinoline alkaloid from Thalictrum glandulosissimum].

A new isoquinoline alkaloid(1) has been isolated from the whole plant of Thalictrum glandulosissimum by using various chromatographic techniques, including silica gel, sephadex, MCI-gel resin, and RP-HPLC, and its structure was determined as 1-(6-hydroxy-7-methylisoquinolin-1-yl) ethantone by physicochemical properties and spectroscopic data. This compound was evaluated for anti-tobacco mosaic virus(TMV) activity. The results showed that it had prominent anti-TMV activity with inhibition rates of 28.4%. This rate was closed to that of positive control.

Protective potential of miR-146a-5p and its underlying molecular mechanism in diverse cancers: a comprehensive meta-analysis and bioinformatics analysis.

BACKGROUND/AIMS: Studies have shown that miR-146a-5p was differentially expressed in diverse cancers, but the associations between miR-146a-5p expression and prognosis across multiple types of cancer as well its potential targets and downstream pathways have not been comprehensively analyzed. In this study, we performed the first meta-analysis of the prognostic value of miR-146a-5p expression in diverse malignancies and explored prospective targets of miR-146a-5p and related signaling pathways. METHODS: A thorough search for articles related to miR-146a-5p was performed, and RNA-seq data from The Cancer Genome Atlas (TCGA) and microarray data from gene expression omnibus profiles were used to collect information about the prognostic value of miR-146a-5p. A comprehensive meta-analysis was conducted. Twelve platforms in miRWalk 2.0 were applied to predict targets of miR-146a-5p. TCGA RNA-seq data were used to validate the inverse relationships between miR-146a-5p and its likely targets. Subsequently, gene ontology and pathway analyses were conducted using Funrich version 3.1.3. Potential protein-protein interaction (PPI) networks were constructed. Potential target genes of miR-146a-5p in lung cancer were validated by RT-qPCR. RESULTS: We included 10 articles in the meta-analysis. In a pooled analysis, the high miR-146a-5p expression group showed a better overall survival in solid cancers, particularly in reproductive system cancers and digestive system cancers. A total of 120 predicted target genes were included in a bioinformatics analysis. Five pathways involving phospholipase C (PLC) and aquaporins (AQPs) were the most significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways. Moreover, the PPI network displayed the related signaling pathways and interactions among proteins. AQP1 and FYN were validated by RT-qPCR to be potential targets of miR-146a-5p in lung cancer. CONCLUSION: There is a close link between high miR-146a-5p expression and better overall survival in 21 types of solid cancer, especially in reproductive system and digestive system cancers. Furthermore, miR-146a-5p could inhibit diverse malignancies by modulating pathways linked to PLC or AQPs. In summary, miR-146a-5p is a potential prognostic biomarker and therapeutic target for various cancers.

Distinguishable Prognostic Signatures of Left- and Right-Sided Colon Cancer: a Study Based on Sequencing Data.

BACKGROUND/AIMS: Left- and right-sided colon cancers are considered to be two different diseases and have altered outcomes. However, specific molecules to predict the prognosis of left- and right-sided colon cancers are currently lacking. METHODS: Expression profiling of colon cancer were downloaded from The Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) of left- and right-sided colon cancers were compared by DESeq analysis. The prognostic values of DEGs were assessed by univariate and multivariate Cox regression. Prognostic index models of two side colon cancers were conducted with prognostic values genes, respectively. Interaction of DEGs was then analyzed by the protein-protein interaction (PPI). Different biology function of two sides of colon cancer was assessed by Gene Set Enrichment Analysis (GSEA). RESULTS: A total of 167 DEGs were identified between left- and right-sided colon cancers based on TCGA data. Using univariate COX regression analysis, five genes (PHACTR3, CKMT2, CYP2W1, ERFE, HOXC4) were related to overall survival in left-sided, and eight distinguishable genes (EREG, ERFE, HOXC6, SLC22A31, TFF1, GFI1, ZG16, RASL10B) in right-sided. Further, left-sided prognostic model was established with PHACTR3 and CKMT2 (HR=2.040; 95%CI=1.004-4.145; P=0.049). Distinguishable prognostic signature for right-sided colon cancer was established based on EREG, ERFE, GFI1, and RASL10B (HR=3.530; 95%CI: 1.934-6.444; P< 0.001) in multivariate analysis. PPI analysis of 167 DEGs showed that CCL5, GNG4, GNLY, GZMH, DRD2, and FASLG genes were at the core of interaction network. In GSEA function analysis, four pathways, including antigen processing and presentation, natural killer cell mediated cytotoxicity, intestinal immune network for Iga production, and type I diabetes mellitus, were significantly enriched in the DEGs of the right-sided colon cancer. CONCLUSIONS: This study constructs a panel of potential prognostic model of left- and right-sided colon cancers, respectively. We also provide molecular biological alterations between left- and right-sided colon cancers.

Biological Effect and Mechanism of the miR-23b-3p/ANXA2 Axis in Pancreatic Ductal Adenocarcinoma.

BACKGROUND/AIMS: Accumulating evidence strongly suggests that microRNAs (miRNAs) modulate the expression of known tumor suppressor genes and oncogenes. In the present study, we found that the proliferation and invasion ability of pancreatic ductal adenocarcinoma (PDAC) cells were significantly suppressed by the overexpression of miR-23b-3p. In addition, there are miR-23b-3p binding sites in annexin A2 (ANXA2). Here, we investigated whether miR-23b-3p had an impact on the progression and metastasis of PDAC by targeting ANXA2. METHODS: Cell proliferation, migration, and invasion, and cell cycle assays were performed to explore the effect of miR-23b-3p on various malignant phenotypes of pancreatic cancer cells. The size of tumors was observed following miR-23b-3p overexpression in an in vivo chick chorioallantoic membrane assay. Dual-luciferase reporter, quantitative real-time PCR, western blot, and immunohistochemical analyses were used to validate the relationship between miR-23b-3p and ANXA2 in vitro. RESULTS: We observed that miR-23b-3p could bind specifically to the 3' untranslated region of ANXA2 and inhibit its expression. MiR-23b-3p overexpression downregulated the expression of ANXA2 mRNA in PDAC cells and limited the size of tumors or even prevented tumor formation. In addition, there was a negative correlation between miR-23b-3p expression and ANXA2 protein expression in clinical specimens. CONCLUSION: MiR-23b-3p inhibits the development and progression of PDAC by regulating ANXA2 directly.

A Preliminary Investigation of PVT1 on the Effect and Mechanisms of Hepatocellular Carcinoma: Evidence from Clinical Data, a Meta-Analysis of 840 Cases, and In Vivo Validation.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) remains a difficult problem that significantly affects the survival of the afflicted patients. Accumulating evidence has demonstrated the functions of long non-coding RNA (lncRNA) in HCC. In the present study, we aimed to explore the potential roles of PVT1 in the tumorigenesis and progression of HCC. METHODS: In this study, quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was applied to detect the differences between PVT1 expression in HCC tissues and cell lines. Then, the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were searched to confirm the relationship between PVT1 expression and HCC. Moreover, a meta-analysis comprising TCGA, GEO, and RT-qPCR was applied to estimate the expression of PVT1 in HCC. Then, cell proliferation was evaluated in vitro. A chicken chorioallantoic membrane (CAM) model of HCC was constructed to measure the effect on tumorigenicity in vivo. To further explore the sponge microRNA (miRNA) of PVT1 in HCC, we used TCGA, GEO, a gene microarray, and target prediction algorithms. TCGA and GEO and the gene microarray were used to select the differentially expressed miRNAs, and the different target prediction algorithms were applied to predict the target miRNAs of PVT1. RESULTS: We found that PVT1 was markedly overexpressed in HCC tissue than in normal liver tissues based on both RT-qPCR and data from TCGA, and the overexpression of PVT1 was closely related to the gender and race of the patient as well as to higher HCC tumor grades. Also, a meta-analysis of 840 cases from multiple sources (TCGA, GEO and the results of our in-house RT-qPCR) showed that PVT1 gained moderate value in discriminating HCC patients from normal controls, confirming the results of RT-qPCR. Additionally, the upregulation of PVT1 could promote HCC cell proliferation in vitro and vivo. Based on the competing endogenous RNA (ceRNA) theory, the PVT1/miR-424-5p/INCENP axis was finally selected for further research. The in silico prediction revealed that there were complementary sequences between PVT1 and miR-424-5p as well as between miR-424-5p and INCENP. Furthermore, a negative correlation trend was found between miR-424-5p and PVT1 based on RT-qPCR, whereas a positive correlation trend was found between PVT1 and INCENP based on data from TCGA. Also, INCENP small interfering RNA (siRNA) could significantly inhibit cell proliferation and viability. CONCLUSIONS: We hypothesized that PVT1 could affect the biological function of HCC cells via targeting miR-424-5p and regulating INCENP. Focusing on the new insight of the PVT1/miR-424-5p/INCENP axis, this study provides a novel perspective for HCC therapeutic strategies.

The LncRNA NEAT1 Accelerates Lung Adenocarcinoma Deterioration and Binds to Mir-193a-3p as a Competitive Endogenous RNA.

BACKGROUND/AIMS: Long noncoding RNAs (lncRNAs) contribute to the development of multiple malignant tumors. Here, we focused on the biological function and underlying molecular mechanism of an lncRNA, nuclear-enriched abundant transcript 1 (NEAT1), in lung adenocarcinoma (LUAD). METHODS: In vitro experiments were conducted to determine the biological effects of NEAT1 in LUAD cells. A luciferase activity reporter assay was performed to corroborate the interaction between NEAT1 and miR-193a-3p. Data from Gene Expression Omnibus (GEO), Oncomine, The Cancer Genome Atlas (TCGA), and our in-house reverse transcription quantitative PCR (RT-qPCR) were combined to examine the expression of NEAT1 and miR-193a-3p in LUAD. To further explore the regulatory mechanism of NEAT1, we searched for putative target genes of miR-193a-3p from 12 online prediction databases and determined genes positively correlated with NEAT1 as candidate targets. Furthermore, we analyzed the expression of these selected genes using data from TCGA. RESULTS: In vitro experiments showed that knockdown of NEAT1 in LUAD cells markedly restrained cell proliferation, invasion, and migration and stimulated cell apoptosis. The dual-luciferase reporter assay demonstrated that miR-193a-3p directly targeted NEAT1 at its 3'-UTR. We then detected NEAT1 and miR-193a-3p in LUAD cells and normal lung epithelial cells and discovered high expression of NEAT1 and low expression of miR-193a-3p in LUAD cell lines. Simultaneously, the pooled results from the GEO, Oncomine, TCGA, and in-house RT-qPCR showed that the NEAT1 expression increased while the miR-193a-3p expression decreased in LUAD tissues versus normal lung tissues. Furthermore, the USF1 gene was not only upregulated in LUAD, but also positively correlated with NEAT1, suggesting that NEAT1 may function as a ceRNA to sponge miR-193a-3p and abrogate the inhibitory effect of miR-193a-3p on USF1. CONCLUSIONS: Our findings indicate that NEAT1 plays important roles in the occurrence and progression of LUAD. It may exert its role by acting as a ceRNA to regulate miR-193a-3p.

A circRNA-miRNA-mRNA network identification for exploring underlying pathogenesis and therapy strategy of hepatocellular carcinoma.

BACKGROUND: Circular RNAs (circRNAs) have received increasing attention in human tumor research. However, there are still a large number of unknown circRNAs that need to be deciphered. The aim of this study is to unearth novel circRNAs as well as their action mechanisms in hepatocellular carcinoma (HCC). METHODS: A combinative strategy of big data mining, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and computational biology was employed to dig HCC-related circRNAs and to explore their potential action mechanisms. A connectivity map (CMap) analysis was conducted to identify potential therapeutic agents for HCC. RESULTS: Six differently expressed circRNAs were obtained from three Gene Expression Omnibus microarray datasets (GSE78520, GSE94508 and GSE97332) using the RobustRankAggreg method. Following the RT-qPCR corroboration, three circRNAs (hsa_circRNA_102166, hsa_circRNA_100291 and hsa_circRNA_104515) were selected for further analysis. miRNA response elements of the three circRNAs were predicted. Five circRNA-miRNA interactions including two circRNAs (hsa_circRNA_104515 and hsa_circRNA_100291) and five miRNAs (hsa-miR-1303, hsa-miR-142-5p, hsa-miR-877-5p, hsa-miR-583 and hsa-miR-1276) were identified. Then, 1424 target genes of the above five miRNAs and 3278 differently expressed genes (DEGs) on HCC were collected. By intersecting the miRNA target genes and the DEGs, we acquired 172 overlapped genes. A protein-protein interaction network based on the 172 genes was established, with seven hubgenes (JUN, MYCN, AR, ESR1, FOXO1, IGF1 and CD34) determined from the network. The Gene Oncology, Kyoto Encyclopedia of Genes and Genomes and Reactome enrichment analyses revealed that the seven hubgenes were linked with some cancer-related biological functions and pathways. Additionally, three bioactive chemicals (decitabine, BW-B70C and gefitinib) based on the seven hubgenes were identified as therapeutic options for HCC by the CMap analysis. CONCLUSIONS: Our study provides a novel insight into the pathogenesis and therapy of HCC from the circRNA-miRNA-mRNA network view.

Analysis of microarrays of miR-34a and its identification of prospective target gene signature in hepatocellular carcinoma.

BACKGROUND: Currently, some studies have demonstrated that miR-34a could serve as a suppressor of several cancers including hepatocellular carcinoma (HCC). Previously, we discovered that miR-34a was downregulated in HCC and involved in the tumorigenesis and progression of HCC; however, the mechanism remains unclear. The purpose of this study was to estimate the expression of miR-34a in HCC by applying the microarray profiles and analyzing the predicted targets of miR-34a and their related biological pathways of HCC. METHODS: Gene expression omnibus (GEO) datasets were conducted to identify the difference of miR-34a expression between HCC and corresponding normal tissues and to explore its relationship with HCC clinicopathologic features. The natural language processing (NLP), gene ontology (GO), pathway and network analyses were performed to analyze the genes associated with the carcinogenesis and progression of HCC and the targets of miR-34a predicted in silico. In addition, the integrative analysis was performed to explore the targets of miR-34a which were also relevant to HCC. RESULTS: The analysis of GEO datasets demonstrated that miR-34a was downregulated in HCC tissues, and no heterogeneity was observed (Std. Mean Difference(SMD) = 0.63, 95% confidence intervals(95%CI):[0.38, 0.88], P < 0.00001; Pheterogeneity = 0.08 I2 = 41%). However, no association was found between the expression value of miR-34a and any clinicopathologic characteristics. In the NLP analysis of HCC, we obtained 25 significant HCC-associated signaling pathways. Besides, we explored 1000 miR-34a-related genes and 5 significant signaling pathways in which CCND1 and Bcl-2 served as necessary hub genes. In the integrative analysis, we found 61 hub genes and 5 significant pathways, including cell cycle, cytokine-cytokine receptor interaction, notching pathway, p53 pathway and focal adhesion, which proposed the relevant functions of miR-34a in HCC. CONCLUSION: Our results may lead researchers to understand the molecular mechanism of miR-34a in the diagnosis, prognosis and therapy of HCC. Therefore, the interaction between miR-34a and its targets may promise better prediction and treatment for HCC. And the experiments in vivo and vitro will be conducted by our group to identify the specific mechanism of miR-34a in the progress and deterioration of HCC.

The suppressive role of miR-542-5p in NSCLC: the evidence from clinical data and in vivo validation using a chick chorioallantoic membrane model.

BACKGROUND: Non-small cell lung cancer (NSCLC) has led to the highest cancer-related mortality for decades. To enhance the efficiency of early diagnosis and therapy, more efforts are urgently needed to reveal the origins of NSCLC. In this study, we explored the effect of miR-542-5p in NSCLC with clinical samples and in vivo models and further explored the prospective function of miR-542-5p though bioinformatics methods. METHODS: A total of 125 NSCLC tissue samples were collected, and the expression of miR-542-5p was detected by qRT-PCR. The relationship between miR-542-5p level and clinicopathological features was analyzed. The effect of miR-542-5p on survival time was also explored with K-M survival curves and Cox's regression. The effect of miR-542-5p on the tumorigenesis of NSCLC was verified with a chick chorioallantoic membrane (CAM) model. The potential target genes were predicted by bioinformatics tools, and relevant pathways were analyzed by GO and KEGG. Several hub genes were validated by Proteinatlas. RESULTS: The expression of miR-542-5p was down-regulated in NSCLC tissues, and consistent results were also found in the subgroups of adenocarcinoma and squamous cell carcinoma. Down-regulation of miR-542-5p was found to be connected with advanced TNM stage, vascular invasion, lymphatic metastasis and EGFR. Survival analyses showed that patients with lower miR-542-5p levels had markedly poorer prognosis. Both tumor growth and angiogenesis were significantly suppressed by miR-542-5p mimic in the CAM model. The potential 457 target genes of miR-542-5p were enriched in several key cancer-related pathways, such as morphine addiction and the cAMP signaling pathway from KEGG. Interestingly, six genes (GABBR1, PDE4B, PDE4C, ADCY6, ADCY1 and GIPR) from the cAMP signaling pathway were confirmed to be overexpressed in NSCLCs tissues. CONCLUSIONS: This evidence suggests that miR-542-5p is a potential tumor-suppressed miRNA in NSCLC, which has the potential to act as a diagnostic and therapeutic target of NSCLC.

Comprehensive analysis of the long noncoding RNA HOXA11-AS gene interaction regulatory network in NSCLC cells.

BACKGROUND: Long noncoding RNAs (lncRNAs) are related to different biological processes in non-small cell lung cancer (NSCLC). However, the possible molecular mechanisms underlying the effects of the long noncoding RNA HOXA11-AS (HOXA11 antisense RNA) in NSCLC are unknown. METHODS: HOXA11-AS was knocked down in the NSCLC A549 cell line and a high throughput microarray assay was applied to detect changes in the gene profiles of the A549 cells. Bioinformatics analyses (gene ontology (GO), pathway, Kyoto Encyclopedia of Genes and Genomes (KEGG), and network analyses) were performed to investigate the potential pathways and networks of the differentially expressed genes. The molecular signatures database (MSigDB) was used to display the expression profiles of these differentially expressed genes. Furthermore, the relationships between the HOXA11-AS, de-regulated genes and clinical NSCLC parameters were verified by using NSCLC patient information from The Cancer Genome Atlas (TCGA) database. In addition, the relationship between HOXA11-AS expression and clinical diagnostic value was analyzed by receiver operating characteristic (ROC) curve. RESULTS: Among the differentially expressed genes, 277 and 80 genes were upregulated and downregulated in NSCLC, respectively (fold change ≥2.0, P < 0.05 and false discovery rate (FDR) < 0.05). According to the degree of the fold change, six upregulated and three downregulated genes were selected for further investigation. Only four genes (RSPO3, ADAMTS8, DMBT1, and DOCK8) were reported to be related with the development or progression of NSCLC based on a PubMed search. Among all possible pathways, three pathways (the PI3K-Akt, TGF-beta and Hippo signaling pathways) were the most likely to be involved in NSCLC development and progression. Furthermore, we found that HOXA11-AS was highly expressed in both lung adenocarcinoma and squamous cell carcinoma based on TCGA database. The ROC curve showed that the area under curve (AUC) of HOXA11-AS was 0.727 (95% CI 0.663-0.790) for lung adenocarcinoma and 0.933 (95% CI 0.906-0.960) for squamous cell carcinoma patients. Additionally, the original data from TCGA verified that ADAMTS8, DMBT1 and DOCK8 were downregulated in both lung adenocarcinoma and squamous cell carcinoma, whereas RSPO3 expression was upregulated in lung adenocarcinoma and downregulated in lung squamous cell carcinoma. For the other five genes (STMN2, SPINK6, TUSC3, LOC100128054, and C8orf22), we found that STMN2, TUSC3 and C8orf22 were upregulated in squamous cell carcinoma and that STMN2 and USC3 were upregulated in lung adenocarcinoma. Furthermore, we compared the correlation between HOXA11-AS and de-regulated genes in NSCLC based on TCGA. The results showed that the HOXA11-AS expression was negatively correlated with DOCK8 in squamous cell carcinoma (r = -0.124, P = 0.048) and lung adenocarcinoma (r = -0.176, P = 0.005). In addition, RSPO3, ADAMTS8 and DOCK8 were related to overall survival and disease-free survival (all P < 0.05) of lung adenocarcinoma patients in TCGA. CONCLUSIONS: Our results showed that the gene profiles were significantly changed after HOXA11-AS knock-down in NSCLC cells. We speculated that HOXA11-AS may play an important role in NSCLC development and progression by regulating the expression of various pathways and genes, especially DOCK8 and TGF-beta pathway. However, the exact mechanism should be verified by functional experiments.

SDF-1/CXCR7 axis regulates the proliferation, invasion, adhesion, and angiogenesis of gastric cancer cells.

BACKGROUND: More recent studies have revealed that chemokine receptor CXCR7 plays an important role in cancer development. However, little is known about the effect of CXCR7 on the process of gastric cancer cell invasion and angiogenesis. The aim of this study is to investigate the expression of CXCR7 in gastric cancer cell lines and to evaluate the role of CXCR7 in the proliferation, invasion, adhesion, and angiogenesis of gastric cancer cells. METHODS: Real-time PCR and Western blotting were used to examine the mRNA and protein levels of CXCR4 and CXCR7 in five gastric cancer cell lines (HGC-27, MGC-803, BGC-823, SGC-7901, and MKN-28). CXCR7-expressing shRNA was constructed and subsequently stably transfected into the human gastric cancer cells. In addition, the effect of CXCR7 inhibition on cell proliferation, invasion, adhesion, VEGF secretion, and tube formation was evaluated. RESULTS: The mRNA and protein of CXCR7 were expressed in all five gastric cancer cell lines; in particular, the expression of CXCR7 was the highest in SGC-7901 cells. Stromal cell-derived factor-1 (SDF-1) was found to induce proliferation, invasion, adhesion, and tube formation. Moreover, the VEGF secretion in SGC-7901 cells was also enhanced by SDF-1 stimulation. These biological effects were inhibited by the silencing of CXCR7 in SGC-7901 cells. CONCLUSIONS: Increased CXCR7 expression was found in gastric cancer cells. Knockdown of CXCR7 expression by transfection with CXCR7shRNA significantly inhibits SGC-7901 cells' proliferation, invasion, adhesion, and angiogenesis. This study provides new insights into the significance of CXCR7 in the invasion and angiogenesis of gastric cancer.

Pacidusin B isolated from Phyllanthus acidus triggers ferroptotic cell death in HT1080 cells.

Cancer cells generally exhibit 'iron addiction' phenotypes, which contribute to their vulnerability to ferroptosis inducers. Ferroptosis is a newly discovered form of programmed cell death caused by iron-dependent lipid peroxidation. In the present study, pacidusin B, a dichapetalin-type triterpenoid from Phyllanthus acidus (L.) Skeels (Euphorbiaceae), induces ferroptosis in the HT1080 human fibrosarcoma cell line. Cells treated with pacidusin B exhibited the morphological characteristic 'ballooning' phenotype of ferroptosis. The biochemical hallmarks of ferroptosis were also observed in pacidusin B-treated cells. Both oxidative stress and ER stress play significant roles in pacidusin B-induced ferroptosis. The activation of the PERK-Nrf2-HO-1 signaling pathway led to iron overload, while inhibition of GPX4 further sensitized cancer cells to ferroptosis. Furthermore, the molecular docking study showed that pacidusin B docked in the same pocket in xCT as the ferroptosis inducer erastin. These results revealed that pacidusin B exerts anticancer effects via inducing ER-mediated ferroptotic cell death.