Repulsive guidance molecule B inhibits metastasis and is associated with decreased mortality in non-small cell lung cancer

Repulsive guidance molecules (RGMs) are co-receptors of bone morphogenetic proteins (BMPs) and programmed death ligand 2 (PD-L2), and might be involved in lung and other cancers. We evaluated repulsive guidance molecule B (RGMB) expression in 165 non-small cell lung cancer (NSCLC) tumors and 22 normal lung tissue samples, and validated the results in an independent series of 131 samples. RGMB was downregulated in NSCLC (P ≤ 0.001), possibly through promoter hypermethylation. Reduced RGMB expression was observed in advanced-stage tumors (P = 0.017) and in tumors with vascular invasion (P < 0.01), and was significantly associated with poor overall survival (39 vs. 62 months, P < 0.001) and with disease-associated patient mortality (P = 0.015). RGMB knockdown promoted cell adhesion, invasion and migration, in both NSCLC cell lines and an in vivo mouse model, which enhanced metastatic potential. Conversely, RGMB overexpression and secretion suppressed cancer progression. The tumor-suppressing effect of RGMB was exerted through inhibition of the Smad1/5/8 pathway. Our results demonstrate that RGMB is an important inhibitor of NSCLC metastasis and that low RGMB expression is a novel predictor or a poor prognosis

Quantitative evaluation of the immunodeficiency of a mouse strain by tumor engraftments

© 2015 Ye et al. Background: The mouse is an organism that is widely used as a mammalian model for studying human physiology or disease, and the development of immunodeficient mice has provided a valuable tool for basic and applied human disease research. Following the development of large-scale mouse knockout programs and genome-editing tools, it has become increasingly efficient to generate genetically modified mouse strains with immunodeficiency. However, due to the lack of a standardized system for evaluating the immuno-capacity that prevents tumor progression in mice, an objective choice of the appropriate immunodeficient mouse strains to be used for tumor engrafting experiments is difficult. Methods: In this study, we developed a tumor engraftment index (TEI) to quantify the immunodeficiency response to hematologic malignant cells and solid tumor cells of six immunodeficient mouse strains and C57BL/6 wild-type mouse (WT). Results: Mice with a more severely impaired immune system attained a higher TEI score. We then validated that the NOD-scid-IL2Rg-/- (NSI) mice, which had the highest TEI score, were more suitable for xenograft and allograft experiments using multiple functional assays. Conclusions: The TEI score was effectively able to reflect the immunodeficiency of a mouse strain.Link_to_subscribed_fulltex

Comparative Analysis of CO2, N2, and Gas Mixture Injection on Asphaltene Deposition Pressure in Reservoir Conditions

CO2 and N2 injection is an effective enhanced oil recovery technology in the oilfield especially for low-permeability and extra low-permeability reservoirs. However, these processes can induce an asphaltene deposition during oil production. Asphaltene-deposition-induced formation damage is a fairly severe problem. Therefore, predicting the likelihood of asphaltene deposition in reservoir conditions is crucial. This paper presents the results of flash separation experiments used to investigate the composition of crude oil in shallow and buried-hill reservoirs. Then, PVTsim Nova is used to simulate the composition change and asphaltene deposition of crude oil. Simulation tests indicate that the content of light components C1-C4 and heavy components C36+ decrease with increasing CO2 and N2 injection volumes. However, the extraction of CO2 is significantly stronger than that of N2. In shallow reservoirs, as the CO2 injection volume increases, the deposition pressure range decreases and asphaltenes are easily deposited. Conversely, the asphaltene deposition pressure of crude oil injected with N2 is higher and will not cause serious asphaltene deposition. When the CO2-N2 injection ratio reaches 1:1, the deposition pressure range shows a significant transition. In buried-hill reservoirs, asphaltene deposition is unlikely to occur with CO2, N2, and a gas mixture injection

Dissolution behavior of fluorine from AOD slag after treatments for volume stabilization

AOD slag samples from steel works of Outokumpu Stainless Company were used to study F-dissolution relating to treatments for volume stabilization. Results from the slag tests and sample characterizations indicate that the slag re-melting with or without reduction and granulation with either water or gas have rather small effects on F leaching, as well as formation of different C2S polymorphs. The chemical composition and cooling condition are the two important parameters to control F leaching from slag samples. These two parameters should be combined together in an optimum way by the steel industry to treat slags for F-immobilization.Validerad; 2014; 20140813 (yang)</p

Determination of serum CA724 levels using fluorescence immunochromatography

Abstract Background Carbohydrate antigen 724 (CA724) is a sensitive and specific indicator for multiple malignant tumors. The aim of this study was to establish a Eu-time resolved fluorescence immunochromatography (Eu-TRFICO) method for quantitative detection of CA724 in serum. Methods Eu-TRFICO strips were optimized and assembled. The sensitivity, specificity and precision were evaluated using CA724 standard dilutions and matrix serum. Meanwhile, the reference interval, comparison, and sensitivity/specificity were performed using clinical negative/positive gastric cancer serum samples. Results The standard curve equation was y = 9.869 x − 154.12 (R 2  = 0.993), and the sensitivity was 0.42 U/mL. The common interferents in serum could not affect the quantitative results with low cross-reactivities (all no more than 1.09%). All average recoveries of the intra- and interbatch ranged from 102.38 to 106.40%, and all CVs were below 10%. The reference interval of the healthy subjects was  9.54 U/mL. Additionally, a high Pearson r (0.9503) and sensitivity/specificity (92.86%/94.20%) were obtained. Conclusion This study prepared Eu-TRFICO strips with high sensitivity, specificity, precision and satisfactory clinical testing performance, which provides more options for clinical quantitative and convenient testing of CA724

De novo assembly and analysis of the transcriptome of Rumex patientia L. during cold stress.

Rumex patientia L. is consumed as a green vegetable in several parts of the world, and can withstand extremely low temperatures (-35°C). However, little or no available genomic data for this species has been reported to date. Here, we used Illumina Hiseq technology for transcriptome assembly in R. patientia under normal and cold conditions to evaluate how it responds to cold stress.After an in-depth RNA-Seq analysis, 115,589 unigenes were produced from the assembled transcripts. Based on similarity search analysis with seven databases, we obtained and annotated 60,157 assembled unigenes to at least one database. In total, 1,179 unigenes that were identified as differentially expressed genes (DEGs), including up-regulated (925) and down-regulated ones (254), were successfully assigned GO annotations and classified into three major metabolic pathways. Ribosome, carbon metabolism, oxidative phosphorylation and biosynthesis of amino acids were the most highly enriched pathways according to KEGG analysis. Overall, 66 up-regulated genes were identified as putatively involved in the response to cold stress, including members of MYB, AP2/ERF, CBF, Znf, bZIP, NAC and COR families.To our knowledge, this investigation was the first to provide a cold-responsive (COR) transcriptome assembly in R. patientia. A large number of potential COR genes were identified, suggesting that this species is suitable for cultivation in northern China. In summary, these data provide valuable information for future research and genomic studies in R. patientia

Correction: De novo assembly and analysis of the transcriptome of Rumex patientia L. during cold stress.

[This corrects the article DOI: 10.1371/journal.pone.0186470.]

Identification and assessment of TCR-T cells targeting an epitope conserved in SARS-CoV-2 variants for the treatment of COVID-19

BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to be a major global public health challenge, with the emergence of variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current vaccines or monoclonal antibodies may not well be protect against infection with new SARS-CoV-2 variants. Unlike antibody-based treatment, T cell-based therapies such as TCR-T cells can target epitopes that are highly conserved across different SARS-CoV-2 variants. Reportedly, T cell-based immunity alone can restrict SARS-CoV-2 replication. METHODS: In this study, we identified two TCRs targeting the RNA-dependent RNA polymerase (RdRp) protein in CD8 + T cells. Functional evaluation by transducing these TCRs into CD8 + or CD4 + T cells confirmed their specificity. RESULTS: Combinations of inflammatory and anti-inflammatory cytokines secreted by CD8 + and CD4 + T cells can help control COVID-19 in patients. Moreover, the targeted epitope is highly conserved in all emerged SARS-CoV-2 variants, including the Omicron. It is also conserved in the seven coronaviruses that infect humans and more broadly in the subfamily Coronavirinae. CONCLUSIONS: The pan-genera coverage of mutant epitopes from the Coronavirinae subfamily by the two TCRs highlights the unique strengths of TCR-T cell therapies in controlling the ongoing pandemic and in preparing for the next coronavirus outbreak