The Cancer Genome Atlas (TCGA) project recently uncovered four molecular subtypes of gastric cancer: Epstein-Barr virus (EBV), microsatellite instability (MSI), genomically stable (GS), and ...chromosomal instability (CIN). However, their clinical significances are currently unknown. We aimed to investigate the relationship between subtypes and prognosis of patients with gastric cancer.
Gene expression data from a TCGA cohort (
= 262) were used to develop a subtype prediction model, and the association of each subtype with survival and benefit from adjuvant chemotherapy was tested in 2 other cohorts (
= 267 and 432). An integrated risk assessment model (TCGA risk score) was also developed.
EBV subtype was associated with the best prognosis, and GS subtype was associated with the worst prognosis. Patients with MSI and CIN subtypes had poorer overall survival than those with EBV subtype but better overall survival than those with GS subtype (
= 0.004 and 0.03 in two cohorts, respectively). In multivariate Cox regression analyses, TCGA risk score was an independent prognostic factor HR, 1.5; 95% confidence interval (CI), 1.2-1.9;
= 0.001. Patients with the CIN subtype experienced the greatest benefit from adjuvant chemotherapy (HR, 0.39; 95% CI, 0.16-0.94;
= 0.03) and those with the GS subtype had the least benefit from adjuvant chemotherapy (HR, 0.83; 95% CI, 0.36-1.89;
= 0.65).
Our prediction model successfully stratified patients by survival and adjuvant chemotherapy outcomes. Further development of the prediction model is warranted.
The lithium–sulfur (Li–S) battery is considered as a promising future energy storage device owing to its high theoretical energy density, low cost of the raw active material (sulfur), and its ...environmental friendliness. On the other hand, there are still challenging issues for the practical applications of Li–S batteries, including low sulfur utilization, poor cyclability, and rate capability. Although considerable efforts are made to overcome the current obstacles in Li–S batteries, one is still far from meeting the requirements for the commercialization of Li–S batteries. This review outlines the recent progress in Li–S batteries based on novel configurations, such as incorporating functional interlayers/separators beyond the approach for preparing novel cathodes, and discusses the role of the configuration in Li–S batteries. The functions of the newly introduced functional interlayer/separator are highlighted to address the problems of Li–S batteries. From classification of the functions, the perspectives and outlook are presented to rationally design a novel functional interlayer/separator for high‐performance Li–S batteries.
The literature on functional interlayers/separators for Li–S batteries is revisited in terms of the functions such as PS‐, e‐, and k‐functions. The related fundamental and practical issues are discussed, and the trade‐off relationships of PS‐, e‐, and k‐functions are drawn out. Based on the discussion, the design rules for balancing the three functions are suggested.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Dementia accompanied by memory loss is considered one of the most common neurodegenerative diseases worldwide, and its prevalence is gradually increasing. Known risk factors for dementia include ...genetic background, certain lifestyle and dietary patterns, smoking, iron overload, insulin resistance, and impaired glucose metabolism in the brain. Here, we review recent evidence on the regulatory role of lipocalin 2 (LCN2) in dementia from various perspectives. LCN2 is a neutrophil gelatinase‐associated protein that influences diverse cellular processes, including the immune system, iron homeostasis, lipid metabolism, and inflammatory responses. Although its functions within the peripheral system are most widely recognized, recent findings have revealed links between LCN2 and central nervous system diseases, as well as novel roles for LCN2 in neurons and glia. Furthermore, LCN2 may modulate diverse pathological mechanisms involved in dementia. Taken together, LCN2 is a promising therapeutic target with which to address the neuropathology of dementia.
The role of LCN2 in neuronal cell damage in the brain of dementia patients.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Objectives
To evaluate radiomics studies according to radiomics quality score (RQS) and Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) to ...provide objective measurement of radiomics research.
Materials and methods
PubMed and Embase were searched for studies published in high clinical imaging journals until December 2018 using the terms “radiomics” and “radiogenomics.” Studies were scored against the items in the RQS and TRIPOD guidelines. Subgroup analyses were performed for journal type (clinical vs. imaging), intended use (diagnostic vs. prognostic), and imaging modality (CT vs. MRI), and articles were compared using Fisher’s exact test and Mann-Whitney analysis.
Results
Seventy-seven articles were included. The mean RQS score was 26.1% of the maximum (9.4 out of 36). The RQS was low in demonstration of clinical utility (19.5%), test-retest analysis (6.5%), prospective study (3.9%), and open science (3.9%). None of the studies conducted a phantom or cost-effectiveness analysis. The adherence rate for TRIPOD was 57.8% (mean) and was particularly low in reporting title (2.6%), stating study objective in abstract and introduction (7.8% and 16.9%), blind assessment of outcome (14.3%), sample size (6.5%), and missing data (11.7%) categories. Studies in clinical journals scored higher and more frequently adopted external validation than imaging journals.
Conclusions
The overall scientific quality and reporting of radiomics studies is insufficient. Scientific improvements need to be made to feature reproducibility, analysis of clinical utility, and open science categories. Reporting of study objectives, blind assessment, sample size, and missing data is deemed to be necessary.
Key Points
• The overall scientific quality and reporting of radiomics studies is insufficient.
• The RQS was low in demonstration of clinical utility, test-retest analysis, prospective study, and open science.
• Room for improvement was shown in TRIPOD in stating study objective in abstract and introduction, blind assessment of outcome, sample size, and missing data categories.
Enhanced expression of the cancer stem cell (CSC) marker, CD133, is closely associated with a higher rate of tumor formation and poor prognosis in hepatocellular carcinoma (HCC) patients. Despite its ...clinical significance, the molecular mechanism underlying the deregulation of CD133 during tumor progression remains to be clarified. Here, we report on a novel mechanism by which interleukin‐6/signal transducer and activator of transcription 3 (IL‐6/STAT3) signaling up‐regulates expression of CD133 and promotes HCC progression. STAT3 activated by IL‐6 rapidly bound to CD133 promoter and increased protein levels of CD133 in HCC cells. Reversely, in hypoxic conditions, RNA interference silencing of STAT3 resulted in decrease of CD133 levels, even in the presence of IL‐6, with a concomitant decrease of hypoxia‐inducible factor 1 alpha (HIF‐1α) expression. Active STAT3 interacted with nuclear factor kappa B (NF‐κB) p65 subunit to positively regulate the transcription of HIF‐1α providing a mechanistic explanation on how those three oncogenes work together to increase the activity of CD133 in a hypoxic liver microenvironment. Activation of STAT3 and its consequent induction of HIF‐1α and CD133 expression were not observed in Toll‐like receptor 4/IL‐6 double‐knockout mice. Long‐term silencing of CD133 by a lentiviral‐based approach inhibited cancer cell‐cycle progression and suppressed in vivo tumorigenicity by down‐regulating expression of cytokinesis‐related genes, such as TACC1, ACF7, and CKAP5. We also found that sorafenib and STAT3 inhibitor nifuroxazide inhibit HCC xenograft formation by blocking activation of STAT3 and expression of CD133 and HIF‐1α proteins. Conclusion: IL‐6/STAT3 signaling induces expression of CD133 through functional cooperation with NF‐κB and HIF‐1α during liver carcinogenesis. Targeting STAT3‐mediated CD133 up‐regulation may represent a novel, effective treatment by eradicating the liver tumor microenvironment. (Hepatology 2015;62:1160‐1173)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Plant microbiota is a key determinant of plant health and productivity. The composition and structure of plant microbiota varies according to plant tissue and compartment, which are specific habitats ...for microbial colonization. To investigate the structural composition of the microbiome associated with tomato roots under natural systems, we characterized the bacterial, archaeal, and fungal communities of three belowground compartments (rhizosphere, endosphere, and bulk soil) of tomato plants collected from 23 greenhouses in 7 geographic locations of South Korea. The microbial diversity and structure varied by rhizocompartment, with the most distinctive community features found in the endosphere. The bacterial and fungal communities in the bulk soil and rhizosphere were correlated with soil physicochemical properties, such as pH, electrical conductivity, and exchangeable cation levels, while this trend was not evident in the endosphere samples. A small number of core bacterial operational taxonomic units (OTUs) present in all samples from the rhizosphere and endosphere represented more than 60% of the total relative abundance. Among these core microbes, OTUs belonging to the genera Acidovorax, Enterobacter, Pseudomonas, Rhizobium, Streptomyces, and Variovorax, members of which are known to have beneficial effects on plant growth, were more relatively abundant in the endosphere samples. A co-occurrence network analysis indicated that the microbial community in the rhizosphere had a larger and more complex network than those in the bulk soil and endosphere. The analysis also identified keystone taxa that might play important roles in microbe-microbe interactions in the community. Additionally, profiling of predicted gene functions identified many genes associated with membrane transport in the endospheric and rhizospheric communities. Overall, the data presented here provide preliminary insight into bacterial, archaeal, and fungal phylogeny, functionality, and interactions in the rhizocompartments of tomato roots under real-world environments.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the brain; however, the roles of GABA in antimicrobial host defenses are largely unknown. Here we demonstrate that ...GABAergic activation enhances antimicrobial responses against intracellular bacterial infection. Intracellular bacterial infection decreases GABA levels in vitro in macrophages and in vivo in sera. Treatment of macrophages with GABA or GABAergic drugs promotes autophagy activation, enhances phagosomal maturation and antimicrobial responses against mycobacterial infection. In macrophages, the GABAergic defense is mediated via macrophage type A GABA receptor (GABA
R), intracellular calcium release, and the GABA type A receptor-associated protein-like 1 (GABARAPL1; an Atg8 homolog). Finally, GABAergic inhibition increases bacterial loads in mice and zebrafish in vivo, suggesting that the GABAergic defense plays an essential function in metazoan host defenses. Our study identified a previously unappreciated role for GABAergic signaling in linking antibacterial autophagy to enhance host innate defense against intracellular bacterial infection.
Herein, a lithium modified Zeolitic Imidazolate Framework-90 (ZIF-90-OLi) was used in a slurry with its organic ligand Imidazole Carboxaldehyde (ICA) water, and glycol to improve the process ...conditions for the capture system and enhance the sorption ability. The performance of this slurry was compared to two other slurries, one based on the parent ZIF-90 nanoporous material with ICA/water/glycol and another based on ZIF-8, its organic ligand Methylimidazole (MIm) and water/glycol. The comparison to ZIF-8 was done because of its use as a ZIF of reference in carbon capture. The maximum sorption capacity for CO2 by the alkali containing slurry was 7.19 mol/L and the maximum CO2/N2 selectivity was 222.93 compared to 2.72 mol/L and 121.63 for the ZIF-8/water/glycol/mlm slurry.
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•ZIF-90 and ZIF-90-OLi were synthesized in house and ZIF-90-OLi CO2 sorption capacity was compared to that for ZIF-90 and ZIF-8.•A ZIF-90-OLi/water/glycol/ICA slurry was used to capture CO2 from N2 and its performance compared to a slurry of ZIF-8.•The desorption energy required to release the captured CO2 from the novel slurry was calculated in this study.•The regeneration of the ZIF-90-OLi, ZIF-90, and ZIF-8, after carbon capture were studied.•The CO2/N2 selectivity for the novel slurry was compared to the ZIF-8/water/glycol/mlm slurry's.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This paper presents a performance analysis and optimization of heat exchanger fin shapes in a thermoelectric power generation system for ship waste heat recovery. It proposes a new curved fin design ...aimed at enhancing heat transfer efficiency and maximizing thermoelectric power generation capacity. Numerical analysis and response surface methodology (RSM) focused on 225 parameters to identify the optimal fin shape. Computational analysis using CFX was conducted on the thermoelectric module system with curved fins. The methodology was verified by comparing and analyzing CFD and PIV experimental results for a curved fin. The paper comprehensively compares the fluid dynamics of curved fins and straight fins, highlighting how curved fins improve heat exchange by creating a tip leak vortex. The results demonstrate the superiority of the curved fin design in terms of heat transfer efficiency and net power generation over the conventional straight fin design.
Diabetes contributes to the onset of various diseases, including cancer and cardiovascular and neurodegenerative diseases. Recent studies have highlighted the similarities and relationship between ...diabetes and dementia as an important issue for treating diabetes-related cognitive deficits. Diabetes-related dementia exhibits several features, including blood-brain barrier disruption, brain insulin resistance, and Aβ over-accumulation. High-mobility group box1 (HMGB1) is a protein known to regulate gene transcription and cellular mechanisms by binding to DNA or chromatin via receptor for advanced glycation end-products (RAGE) and toll-like receptor 4 (TLR4). Recent studies have demonstrated that the interplay between HMGB1, RAGE, and TLR4 can impact both neuropathology and diabetic alterations. Herein, we review the recent research regarding the roles of HMGB1-RAGE-TLR4 axis in diabetes-related dementia from several perspectives and emphasize the importance of the influence of HMGB1 in diabetes-related dementia.
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•HMGB1, RAGE and TLR4 lead to BBB disruption in diabetes related dementia brain.•HMGB1, RAGE, and TLR4 aggravate brain insulin resistance in diabetes related dementia brain.•HMGB1, RAGE, and TLR4 exacerbate high amyloid-beta toxicity in diabetes related dementia brain.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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