Identification of a Potentially Functional microRNA-mRNA Regulatory Network in Lung Adenocarcinoma Using a Bioinformatics Analysis

Background Lung adenocarcinoma (LUAD) is a common lung cancer with a high mortality, for which microRNAs (miRNAs) play a vital role in its regulation. Multiple messenger RNAs (mRNAs) may be regulated by miRNAs, involved in LUAD tumorigenesis and progression. However, the miRNA-mRNA regulatory network involved in LUAD has not been fully elucidated. Methods Differentially expressed miRNAs and mRNA were derived from the Cancer Genome Atlas (TCGA) dataset in tissue samples and from our microarray data in plasma (GSE151963). Then, common differentially expressed (Co-DE) miRNAs were obtained through intersected analyses between the above two datasets. An overlap was applied to confirm the Co-DEmRNAs identified both in targeted mRNAs and DEmRNAs in TCGA. A miRNA-mRNA regulatory network was constructed using Cytoscape. The top five miRNA were identified as hub miRNA by degrees in the network. The functions and signaling pathways associated with the hub miRNA-targeted genes were revealed through Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The key mRNAs in the protein-protein interaction (PPI) network were identified using the STRING database and CytoHubba. Survival analyses were performed using Gene Expression Profiling Interactive Analysis (GEPIA). Results The miRNA-mRNA regulatory network consists of 19 Co-DEmiRNAs and 760 Co-DEmRNAs. The five miRNAs (miR-539-5p, miR-656-3p, miR-2110, let-7b-5p, and miR-92b-3p) in the network were identified as hub miRNAs by degrees (>100). The 677 Co-DEmRNAs were targeted mRNAs from the five hub miRNAs, showing the roles in the functional analyses of the GO analysis and KEGG pathways (inclusion criteria: 836 and 48, respectively). The PPI network and Cytoscape analyses revealed that the top ten key mRNAs were NOTCH1, MMP2, IGF1, KDR, SPP1, FLT1, HGF, TEK, ANGPT1, and PDGFB. SPP1 and HGF emerged as hub genes through survival analysis. A high SPP1 expression indicated a poor survival, whereas HGF positively associated with survival outcomes in LUAD. Conclusion This study investigated a miRNA-mRNA regulatory network associated with LUAD, exploring the hub miRNAs and potential functions of mRNA in the network. These findings contribute to identify new prognostic markers and therapeutic targets for LUAD patients in clinical settings.Peer reviewe

Features of the gamma-ray pulsar halo HESS J1831−-098

Gamma-ray pulsar halos are ideal indicators of cosmic-ray propagation in localized regions of the Galaxy and electron injection from pulsar wind nebulae. HESS~J1831$-$098 is a candidate pulsar halo observed by both H.E.S.S. and HAWC experiments. We adopt the flux map of the H.E.S.S. Galactic plane survey and the spectrum measurements of H.E.S.S. and \textit{Fermi}-LAT to study HESS~J1831$-$098. We find that HESS~J1831$-$098 meets all the criteria for a pulsar halo. The diffusion coefficient inside the halo and the conversion efficiency from the pulsar spin-down energy to the electron energy are both similar to the Geminga halo, a canonical pulsar halo. The injection spectrum can be well described by an exponentially-cutoff power law. However, the needed power-law term is very hard with $p\lesssim1$ if the diffusion coefficient is spatially and temporally independent. Considering the possible origins of the slow-diffusion environment, we adopt the two-zone diffusion model and the time-delayed slow-diffusion model. Both the models can interpret the H.E.S.S. and \textit{Fermi}-LAT results with a milder $p$. A modified injection time profile may have a similar effect.Comment: 15 pages (one column), 4 figures, 1 tabl

Host structural stabilization of Li1.232Mn0.615Ni0.154O2 through K-doping attempt: toward superior electrochemical performances

Lithium-rich layered cathodes are known famously for its superior capacity over traditional layered oxides but trapped for lower initial coulombic efficiency, poorer rate capability and worse cyclic stability in spite of diverse attempts. Herein, a new K-stabilized Li-rich layered cathode synthesized through a simple oxalate co-precipitation is reported for its super electrochemical performances. Compared with pristine Li-rich layered cathode, K-stabilized one reaches a higher initial coulombic efficiency of 87% from 76% and outruns for 94% of capacity retention and 244 mAh g-1 of discharge capacity at 0.5C after 100 cycles. Moreover, 133 mAh g-1 of discharge capacity can be delivered even charged at 10C showing a highly-improved rate capability. X-ray diffraction and electrochemical impedance spectroscopy tests show that enlarged Li slab layer caused by K+ accommodation can provide facile Li+ diffusion paths and facilitate Li+ migration from the crystal lattice. As a consequence, the introduction of K+ in the host layered structure can inhibit the detrimental spinel structure growth during cycling. Therefore, the K-stabilized Li-rich layered materials can be considered to be an attractive alternative to meet with the higher power and energy density demands of advanced lithium-ion battery

Research on Key Factors Affecting Storage Quality of Peanut Nougat and Improvement Methods

To explore reasons and solutions for the rancidity of peanut nougat in storage, this paper investigates the oxidation stability of shelled peanuts and unshelled peanut stored in different temperatures and the quality of nougats prepared by adding peanuts treated in different ways. The results show that when raw peanuts are stored at temperatures of 25 ℃, 37 ℃ and 60 ℃, the oxidation rate of shelled raw peanuts is slower than that of unshelled raw peanuts. The peroxide value of shelled peanuts does not change significantly and is stable below 2 mmol/kg, while the peroxide value of roasted cooked peanuts changes faster when stored at 60 ℃, and the change of the shelled peanuts is slower than that of the unshelled peanuts. The oxidation rate of baked shelled peanuts is slower than that of unshelled, which could potentially prolong the shelf life of peanut nougats made of them

TVIR: a comprehensive vegetable information resource database for comparative and functional genomic studies

Vegetables are an indispensable part of the daily diet of humans. Therefore, it is vital to systematically study the genomic data of vegetables and build a platform for data sharing and analysis. In this study, a comprehensive platform for vegetables with a user-friendly Web interface—The Vegetable Information Resource (TVIR, http://tvir.bio2db.com)—was built based on the genomes of 59 vegetables. TVIR database contains numerous important functional genes, including 5215 auxin genes, 2437 anthocyanin genes, 15 002 flowering genes, 79 830 resistance genes, and 2639 glucosinolate genes of 59 vegetables. In addition, 2597 N6-methyladenosine (m6A) genes were identified, including 513 writers, 1058 erasers, and 1026 readers. A total of 2 101 501 specific clustered regularly interspaced short palindromic repeat (CRISPR) guide sequences and 17 377 miRNAs were detected and deposited in TVIR database. Information on gene synteny, duplication, and orthologs is also provided for 59 vegetable species. TVIR database contains 2 346 850 gene annotations by the Swiss-Prot, TrEMBL, Gene Ontology (GO), Pfam, and Non-redundant (Nr) databases. Synteny, Primer Design, Blast, and JBrowse tools are provided to facilitate users in conducting comparative genomic analyses. This is the first large-scale collection of vegetable genomic data and bioinformatic analysis. All genome and gene sequences, annotations, and bioinformatic results can be easily downloaded from TVIR. Furthermore, transcriptome data of 98 vegetables have been collected and collated, and can be searched by species, tissues, or different growth stages. TVIR is expected to become a key hub for vegetable research globally. The database will be updated with newly assembled vegetable genomes and comparative genomic studies in the future

Timing Is Critical for an Effective Anti-Metastatic Immunotherapy: The Decisive Role of IFNγ/STAT1-Mediated Activation of Autophagy

BACKGROUND: Immunotherapy is often recommended as an adjuvant treatment to reduce the chance of cancer recurrence or metastasis. Interestingly, timing is very important for a successful immunotherapy against metastasis, although the precise mechanism is still unknown. METHODS AND FINDINGS: Using a mouse model of melanoma metastasis induced by intravenous injection of B16-F10 cells, we investigated the mechanism responsible for the diverse efficacy of the prophylactic or therapeutic TLR4 and TLR9 agonist complex against metastasis. We found that the activation of TLR4 and TLR9 prevented, but did not reverse, metastasis because the potency of this combination was neither sufficient to overcome the tumor cell-educated immune tolerance nor to induce efficacious autophagy in tumor cells. The prophylactic application of the complex promoted antimetastatic immunity, leading to the autophagy-associated death of melanoma cells via IFNγ/STAT1 activation and attenuated tumor metastasis. IFNγ neutralization reversed the prophylactic benefit induced by the complex by suppressing STAT1 activation and attenuating autophagy in mice. However, the therapeutic application of the complex did not suppress metastasis because the complex could not reverse tumor cell-induced STAT3 activation and neither activate IFNγ/STAT1 signaling and autophagy. Suppressing STAT3 activation with the JAK/STAT antagonist AG490 restored the antimetastatic effect of the TLR4/9 agonist complex. Activation of autophagy after tumor inoculation by using rapamycin, with or without the TLR4/9 agonist complex, could suppress metastasis. CONCLUSION AND SIGNIFICANCE: Our studies suggest that activation of IFNγ/STAT1 signaling and induction of autophagy are critical for an efficacious anti-metastatic immunotherapy and that autophagy activators may overcome the timing barrier for immunotherapy against metastasis