Real networks exhibit heterogeneous nature with nodes playing far different roles in structure and function. To identify vital nodes is thus very significant, allowing us to control the outbreak of ...epidemics, to conduct advertisements for e-commercial products, to predict popular scientific publications, and so on. The vital nodes identification attracts increasing attentions from both computer science and physical societies, with algorithms ranging from simply counting the immediate neighbors to complicated machine learning and message passing approaches. In this review, we clarify the concepts and metrics, classify the problems and methods, as well as review the important progresses and describe the state of the art. Furthermore, we provide extensive empirical analyses to compare well-known methods on disparate real networks, and highlight the future directions. In spite of the emphasis on physics-rooted approaches, the unification of the language and comparison with cross-domain methods would trigger interdisciplinary solutions in the near future.
Transition metal dichalcogenide materials have been explored extensively as catalysts to negotiate the hydrogen evolution reaction, but they often run at a large excess thermodynamic cost. Although ...activating strategies, such as defects and composition engineering, have led to remarkable activity gains, there remains the requirement for better performance that aims for real device applications. We report here a phosphorus-doping-induced phase transition from cubic to orthorhombic phases in CoSe
. It has been found that the achieved orthorhombic CoSe
with appropriate phosphorus dopant (8 wt%) needs the lowest overpotential of 104 mV at 10 mA cm
in 1 M KOH, with onset potential as small as -31 mV. This catalyst demonstrates negligible activity decay after 20 h of operation. The striking catalysis performance can be attributed to the favorable electronic structure and local coordination environment created by this doping-induced structural phase transition strategy.
Chemo-resistance is a huge obstacle encountered in the osteosarcoma (OS) treatment. Protein-coding mRNAs, as well as non-coding RNAs (ncRNAs), including long ncRNA (lncRNA), circular RNA (circRNA), ...and microRNA (miRNA), have been demonstrated to play an essential role in the regulation of cancer biology. However, the comprehensive expression profile and competing endogenous RNA (ceRNA) regulatory network between mRNAs and ncRNAs in the OS chemo-resistance still remain unclear. In the current study, we developed whole-transcriptome sequencing (RNA sequencing RNA-seq) in the three paired multi-drug chemo-resistant and chemo-sensitive OS cell lines to comprehensively identify differentially expressed lncRNAs, circRNAs, miRNAs, and mRNAs. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed for mRNAs with significantly different expression. Then the ceRNA networks combining lncRNAs, circRNAs, miRNAs, and mRNAs were predicted and constructed on the basis of the authoritative miRanda and TargetScan databases combined with the widely accepted vital drug resistance-related genes and signal transduction pathways. In addition, two constructed ceRNA regulatory pathways, lncRNAMEG3/hsa-miR-200b-3p/AKT2 and hsa_circ_0001258/hsa-miR-744-3p/GSTM2, were randomly selected and validated by real-time qPCR, RNA immunoprecipitation (RIP), RNA pull-down assay, and dual luciferase reporter gene system. Taken together, our findings may provide new evidence for the underlying mechanism of OS chemo-resistance and uncover some novel targets for reversing it.
Zhang et al. identify the comprehensive expression profile and competing endogenous RNA (ceRNA) regulatory network between mRNAs and ncRNAs (long ncRNA lncRNA, circular RNA (circRNA), and microRNA miRNA) in the OS chemo-resistance by whole-transcriptome RNA sequencing, bioinformatics analysis, and assay validation in the three paired multi-drug chemo-resistant and chemo-sensitive OS cell lines.
Calcineurin B-like proteins (CBLs) are ubiquitous Ca.sup.2+ sensors that mediate plant responses to various stress and developmental processes by interacting with CBL-interacting protein kinases ...(CIPKs). CBLs and CIPKs play essential roles in acclimatization of crop plants. However, evolution of these two gene families in the genus Medicago is poorly understood. A total of 68 CBL and 135 CIPK genes have been identified in five genomes from Medicago. Among these genomes, the gene number of CBLs and CIPKs shows no significant difference at the haploid genome level. Phylogenetic and comprehensive characteristic analyses reveal that CBLs and CIPKs are classified into four clades respectively, which is validated by distribution of conserved motifs. The synteny analysis indicates that the whole genome duplication events (WGDs) have contributed to the expansion of both families. Expression analysis demonstrates that two MsCBLs and three MsCIPKs are specifically expressed in roots, mature leaves, developing flowers and nitrogen fixing nodules of Medicago sativa spp. sativa, the widely grown tetraploid species. In particular, the expression of these five genes was highly up-regulated in roots when exposed to salt and drought stress, indicating crucial roles in stress responses. Our study leads to a comprehensive understanding of evolution of CBL and CIPK gene families in Medicago, but also provides a rich resource to further address the functions of CBL-CIPK complexes in cultivated species and their closely related wild relatives.
High frequency of recurrence is the major cause of the poor outcomes for patients with hepatocellular carcinoma (HCC). microRNA (miR)-182-5p emerged as a high-priority miRNA in HCC and was found to ...be related to HCC metastasis. Whether the expression of miR-182-5p in tumor tissue correlated with early recurrence in HCC patients underwent curative surgery was unknown.
Real-time PCR (RT-PCR) and in situ hybridization (ISH) were conducted to assess the expression of miR-182-5p in HCC cells and tissues. Cell Counting Kit-8 (CCK-8), transwell assays were performed to detected cells proliferation and migration ability. Flow cytometry assays were used to detect cell apoptosis rate, and xenograft model was employed to study miR-182-5p in HCC growth and lung metastasis. The target of miR-182-5p was validated with a dual-luciferase reporter assay and western blotting. Immunohistochemistry, immumoblotting, and immunoprecipitation were performed to test relative protein expression.
We showed that high expression of miR-182-5p in tumor tissues correlated with poor prognosis as well as early recurrence in HCC patients underwent curative surgery. miR-182-5p enhanced motility and invasive ability of HCC cells both in vitro and in vivo. miR-182-5p directly targets 3'-UTR of FOXO3a and repressed FOXO3a expression, activating AKT/FOXO3a pathway to promote HCC proliferation. Notably, miR-182-5p activated Wnt/β-catenin signaling by inhibiting the degradation of β-catenin and enhancing the interaction between β-catenin and TCF4 which was mediated by repressed FOXO3a.
Consistently, miR-182-5p can be a potential predictor of early recurrence for HCC patients underwent curative surgery, and FOXO3a plays a key mediator in miR-182-5p induced HCC progression.
Objectives
The tyrosine kinase inhibitor (TKI)-sensitive mutations of the epidermal growth factor receptor (EGFR) gene is essential in the treatment of lung adenocarcinoma. To overcome the difficulty ...of EGFR gene test in situations where surgery and biopsy samples are too risky to obtain, we tried a noninvasive imaging method using radiomics features and random forest models.
Methods
Five hundred three lung adenocarcinoma patients who received surgery-based treatment were included in this study. The diagnosis and EGFR gene test were based on resections. TKI-sensitive mutations were found in 60.8% of the patients. CT scans before any invasive operation were gathered and analyzed to extract quantitative radiomics features and build random forest classifiers to identify EGFR mutants from wild types. Clinical features (sex and smoking history) were added to the image-based model. The model was trained on a set of 345 patients and validated on an independent test group (
n
= 158) using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity.
Results
The performance of the random forest model with 94 radiomics features reached an AUC of 0.802. Its AUC was further improved to 0.828 by adding sex and smoking history. The sensitivity and specificity are 60.6% and 85.1% at the best diagnostic decision point.
Conclusion
Our results showed that radiomics could not only reflect the genetic differences among tumors but also have diagnostic value and the potential to be a diagnostic tool.
Key Points
•
Radiomics provides a potential noninvasive method for the prediction of EGFR mutation status.
•
In situations where surgeries and biopsy are not available, CT image-based radiomics models could help to make treatment decisions.
•
The accuracy, sensitivity, and specificity still need to be improved before the image-based EGFR identifier could be used in clinics.
Abstract Recent efforts have revealed that numerous natural antisense lncRNAs play a crucial role in the regulation of cancer biology. Here, based on our previous study, we further identified that ...the lncRNA FOXC2-AS1 and its antisense transcript FOXC2 were positively up-regulated in doxorubicin-resistant osteosarcoma cell lines and tissues, correlate with poor prognosis and promote doxorubicin resistance in osteosarcoma cells in vitro and in vivo . In addition, FOXC2-AS1 and FOXC2 are mainly located in the cytoplasm and form an RNA–RNA double-stranded structure in the overlapping region, which is necessary for FOXC2-AS1 to regulate the expression of FOXC2 at both the transcription and post-transcription levels. In addition, transcription factor FOXC2 also contributes to doxorubicin resistance through inducing the expression of the classical multi-drug resistance-related ABCB1 gene similar to FOXC2-AS1. Thus, we concluded that the lncRNA FOXC2-AS1 may promote doxorubicin resistance in OS by increasing the expression of transcription factor FOXC2, further facilitating ABCB1 expression. These findings demonstrate the potential underlying mechanism of FOXC2-AS1 in the regulation of doxorubicin resistance in OS and possibly provide a novel reversing target.
Abstract
Recently developed solid-state catalysts can mediate carbon dioxide (CO
2
) electroreduction to valuable products at high rates and selectivities. However, under commercially relevant ...current densities of > 200 milliamperes per square centimeter (mA cm
−2
), catalysts often undergo particle agglomeration, active-phase change, and/or element dissolution, making the long-term operational stability a considerable challenge. Here we report an indium sulfide catalyst that is stabilized by adding zinc in the structure and shows dramatically improved stability. The obtained ZnIn
2
S
4
catalyst can reduce CO
2
to formate with 99.3% Faradaic efficiency at 300 mA cm
−2
over 60 h of continuous operation without decay. By contrast, similarly synthesized indium sulfide without zinc participation deteriorates quickly under the same conditions. Combining experimental and theoretical studies, we unveil that the introduction of zinc largely enhances the covalency of In-S bonds, which “locks” sulfur—a catalytic site that can activate H
2
O to react with CO
2
, yielding HCOO* intermediates—from being dissolved during high-rate electrolysis.
Studies of gene rearrangements and the consequent oncogenic fusion proteins have laid the foundation for targeted cancer therapy. To identify oncogenic fusions associated with glioma progression, we ...catalogued fusion transcripts by RNA-seq of 272 gliomas. Fusion transcripts were more frequently found in high-grade gliomas, in the classical subtype of gliomas, and in gliomas treated with radiation/temozolomide. Sixty-seven in-frame fusion transcripts were identified, including three recurrent fusion transcripts: FGFR3-TACC3, RNF213-SLC26A11, and PTPRZ1-MET (ZM). Interestingly, the ZM fusion was found only in grade III astrocytomas (1/13; 7.7%) or secondary GBMs (sGBMs, 3/20; 15.0%). In an independent cohort of sGBMs, the ZM fusion was found in three of 20 (15%) specimens. Genomic analysis revealed that the fusion arose from translocation events involving introns 3 or 8 of PTPRZ and intron 1 of MET. ZM fusion transcripts were found in GBMs irrespective of isocitrate dehydrogenase 1 (IDH1) mutation status. sGBMs harboring ZM fusion showed higher expression of genes required for PIK3CA signaling and lowered expression of genes that suppressed RB1 or TP53 function. Expression of the ZM fusion was mutually exclusive with EGFR overexpression in sGBMs. Exogenous expression of the ZM fusion in the U87MG glioblastoma line enhanced cell migration and invasion. Clinically, patients afflicted with ZM fusion harboring glioblastomas survived poorly relative to those afflicted with non-ZM-harboring sGBMs (P < 0.001). Our study profiles the shifting RNA landscape of gliomas during progression and reveled ZM as a novel, recurrent fusion transcript in sGBMs.
Circular RNAs (circRNAs) represent a widespread class of non-coding RNAs generated from back-splicing, with a circular loop structure. Many circRNAs have been reported to play essential roles in ...cancer development and have the potential to serve as a novel class of biomarkers for clinical diagnosis. However, the role of circRNA in osteosarcoma (OS) remains largely unknown. In the current study, we examined the expression level of circular RNA PVT1 (circPVT1), previously screened and identified the oncogenic role in gastric cancer, in OS and found that circPVT1 was significantly up-regulated in the OS tissues, serums and chemoresistant cell lines, correlated with poor prognosis of OS patients. Besides, ROC curve demonstrated that circPVT1 may be a better diagnostic biomarker than alkaline phosphatase (ALP) in OS with more sensitivity and specificity. In addition, functional assays revealed that circPVT1 knockdown by siRNA could weaken the resistance to doxorubicin and cisplatin of OS cells through decreasing the expression of classical drug resistance-related gene ABCB1. These findings may provide a new insight into the role of circPVT1 as a biomarker for the diagnosis and treatment target of OS.
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