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Background: Microsatellite instability-high (MSI-H) tumors are distinct molecular subtypes in gastric cancer. However, a few studies have comprehensively reported the molecular features of MSI-H tumors and their prognostic factors in locally advanced gastric cancer. This study aimed to clarify the molecular features and prognostic factors of locally advanced MSI-H gastric cancer. Methods: This study included 499 patients with locally advanced gastric cancer who underwent radical gastrectomy. We evaluated the MSI status and compared with previously published whole-exome sequencing, panel sequencing, and gene expression profiling data. Clinicopathological characteristics and molecular profiles were compared between patients with MSI-H and microsatellite stable (MSS) gastric cancer. A subgroup analysis of survival was performed in patients with MSI-H gastric cancer. Results: MSI-H tumors were detected in 79 of 499 patients (15.8%). MSI-H tumors were associated with an increased tumor mutational burden, MLH1 downregulation, CD274 (PD-L1) upregulation, and enrichment of cell cycle pathways. Among patients with MSI-H gastric cancer, the disease-specific survival (DSS) tended to be better in the surgery plus tegafur, gimeracil, and oteracil potassium (S-1) adjuvant chemotherapy group than in the surgery alone group, especially for stage III patients. Furthermore, DSS was better in the T cell-inflamed gene expression signature-high group, and it tended to be worse in the non-solid type poorly differentiated adenocarcinoma group. Conclusions: The molecular features and prognostic factors of locally advanced MSI-H gastric cancer were clarified. S-1 adjuvant chemotherapy appears to be beneficial, and the T cell-inflamed gene expression signature and histopathological type are prognostic factors in MSI-H tumors. [ABSTRACT FROM AUTHOR]

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Deep eutectic solvents may develop a pivotal role in future technologies considering sustainability and safety as pivotal aspects for chemistry developments. The possible application of these fluids for heat transfer operations is of great relevance for which the knowledge of thermal properties such as thermal conductivity is required as well as inferring structure–property relationships which allow reverse design of the fluids according to the technological requirements. Considering the technological relevance of this property, the available literature on the thermal conductivity for deep eutectic solvents is critically discussed showing strengths and weaknesses. The analysis of the state-of-the-art shows the future needs in this research field considering the application of these solvents for thermal-related technologies. The review indicates the scarcity of reliable experimental data and the need of predictive methods, which could be used for process design and solvent screening purposes. Likewise, considering the relevance of developing predictive methods for in silico design of these fluids according to industrial needs, the available predictive theoretical approaches are analysed showing their reliability as well as future needs. Finally, considering the need of developing suitable and reliable structure–property relationship, the molecular level basis of thermal conductivity in deep eutectic solvents is discussed, showing the role of hydrogen bonding and the effects rising from the involved hydrogen bond donors and acceptors as well as the eutectic compositions. This work reports the first literature review and analysis on thermal conductivity for deep eutectic solvents considering an experimental and theoretical approach as well as providing support for the molecular basis of this technologically relevant property, thus contributing to the development of environmentally friendly materials for thermal-related technologies. [ABSTRACT FROM AUTHOR]

In this work, the relatively thermal conductivity of metal oxide-based ethylene glycol nanofluids is being predicted by using quantitative structure–property relationship methodology. The structural features of studied nanoparticles are represented by quasi-SMILES which is a coded linear structure. The gathered dataset includes ten types of nanoparticles (including Al2O3, MgO, TiO2, ZnO, Co3O4, CeO2, CuO, Fe2O3, Fe3O4, and SnO2) suspended in the same base fluid, ethylene glycol. The calculated optimal descriptors acquired by applying the Monte Carlo method in the free software available on the Web (named CORAL) and four random splits into the training, invisible, calibration, and validation sets were appraised. The statistical characteristics confirmed the predictive power and reliability of the developed models; all splits had R m 2 ¯ more than 0.5 and Δ R m 2 less than 0.2, and also the validation set showed the correlation coefficient (R2) in ranges 0.8611–0.6816 and cross-validated correlation coefficient (Q2) in ranges 0.8518–0.6668. The presented models accurately predicted the thermal conductivity of all considered nanofluids, and the technique is expected to provide a novel way for future theoretical projects. [ABSTRACT FROM AUTHOR]

Alternative splicing (AS) is a ubiquitous mechanism in which pre-mRNA can be spliced into divergent variants and involved in carcinogenesis and progression in several cancers. In the present study, we systematically profiled prognostic AS signatures involving both low grade glioma (LGG) and glioblastoma (GBM) and investigated the association of AS signatures with tumor grade and IDH1 status in glioma. Percent spliced in (PSI) values and corresponding clinical data were obtained from TCGA SpliceSeq and TCGA data portal, respectively. Prognostic AS signatures were identified using univariate and stepwise multivariate Cox regression. Heatmap analysis was performed based on prognostic AS signatures. A prognostic signature was established with 69 and 88 AS events, including specific splicing events of MUTYH, STEAP3, and CTNNB1, in LGG and GBM cohorts, respectively. The area under the curve (AUC) of the prediction model was 0.968 at 2000 days of overall survival (OS) in the LGG cohort and 0.966 at 450 days of OS in the GBM cohort. In addition, these prognostic AS signatures could complement current molecular classification, such as IDH1 mutation, 1p/19q codeletion, and ATRX loss, of glioma and further identify potential subgroups of glioma with the same molecular features. In conclusion, our study systematically profiled prognostic AS events involving both low grade glioma and glioblastoma for the first time, which also shed light on the crosstalk between AS signatures and molecular features of glioma. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to determine the molecular features and clinical outcomes of young patients with non-small cell lung cancer (NSCLC) harboring ALK fusion genes. Methods: We interrogated the genomic profile of 1652 patients with lung cancer who underwent targeted next-generation sequencing to screen for candidate oncogenic drivers using histological specimens acquired from January 2016 to December 2018. Results: ALK fusions were identified in 101 NSCLC patients, and 52 of them were diagnosed before the age of 50 years (52/367, 14.2%). Of the 52 patients with early-onset disease, 22 (42.3%) were male and 43 (82.7%) never smoked; the median patient age was 44 years (range 28–50 years). The most frequently occurring ALK fusion partner was EML4, which was identified in 80.8% (42/52) of young patients. Compared to the older patients, patients with early-onset disease were more likely to harbor EML4-ALK variant 1 (38.5% vs. 14.3%; P = 0.007). We also identified rare ALK fusions, including CHRNA7-ALK, TACR1-ALK, HIP1-ALK, DYSF-ALK and ITGAV-ALK, in patients with early-onset disease, and patients with these fusions responded well to crizotinib treatment. A statistically significant difference was observed in progression-free survival (PFS) between the young patients and older patients who received crizotinib as the first-line therapy (17.5 months vs 9.0 months, P = 0.048). However, the median PFS of young patients harboring concurrent TP53 mutations was only 6.2 months. Conclusion: Unique genetic characteristics were found in ALK-rearranged NSCLC patients with early disease onset, and these patients responded better to crizotinib and had longer PFS compared to patients with later disease onset. However, patients with concomitant TP53 mutations may not have a significant response to treatment. [ABSTRACT FROM AUTHOR]

Bloodstains found at crime scenes contain immense information about the crime; thus, studies involving analysis of small molecules in bloodstains have been conducted. However, most of these studies have not accounted for the difference in the results of small molecule analysis due to the surface of bloodstains. To evaluate the "surface effect," we prepared bloodstains on seven surfaces, including both absorbent and non-absorbent surfaces, and performed global small molecule analysis by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). We used three indicators: (1) count recovery rate (%) of molecular features (MFs), (2) the number of MFs extracted from the surface without bloodstains, and (3) difference in abundance recovery rate (%) of MFs, to determine the ranking of the seven surfaces in the order of their similarity with blood. We also confirmed the correlation between each surface and blood through multivariate analysis. We found that the non-absorbent surfaces ranked better than the absorbent surfaces; wooden flooring was ranked as the most efficient surface, followed by stainless, vinyl flooring, glass, tile, filter paper, and mixed cotton. This study will help in the selection of the most efficient surface for collection of bloodstains for small molecule analysis from a crime scene. This is the first study to identify the effects of surface on extraction of global small molecules from bloodstains; it will help forensic scientists in obtaining more accurate information from small molecules present in the bloodstains collected at the field. [ABSTRACT FROM AUTHOR]

Key message: Conserved motif, gene structure, expression and interaction analysis of C2H2-ZFPs in Brassica rapa, and identified types of genes may play essential roles in flower development, and BrZFP38 was proved to function in flower development by affecting pollen formation. Flower development plays a central role in determining the reproduction of higher plants, and Cys2/His2 zinc-finger proteins (C2H2-ZFPs) widely participate in the transcriptional regulation of flower development. C2H2-ZFPs with various structures are the most widespread DNA-binding transcription factors in plants. In this study, conserved protein motif and gene structures were analyzed to investigate systematically the molecular features of Brassica rapa C2H2-ZFP genes. Expression of B. rapa C2H2-ZFPs in multiple tissues showed that more than half of the family members with different types ZFs were expressed in flowers. The specific expression profiles of these C2H2-ZFPs in different B. rapa floral bud stages were further evaluated to identify their potential roles in flower development. Interaction networks were constructed in B. rapa based on the orthology of flower-related C2H2-ZFP genes in Arabidopsis. The putative cis-regulatory elements in the promoter regions of these C2H2-ZFP genes were thoroughly analyzed to elucidate their transcriptional regulation. Results showed that the orthologs of known-function flower-related C2H2-ZFP genes were conserved and differentiated in B. rapa. A C2H2-ZFP was proved to function in B. rapa flower development. Our study provides a systematic investigation of the molecular characteristics and expression profiles of C2H2-ZFPs in B. rapa and promotes further work in function and transcriptional regulation of flower development. [ABSTRACT FROM AUTHOR]

Recombinant Mycobacterium bovis BCG vaccines (rBCG) were first developed in the 1990s as a means of expressing antigens from multiple pathogens. This review examines the key structural factors of recombinant M. bovis that influence the expression of the heterologous antigens and the generation of genetic and functional stability in rBCG, which are crucial for inducing strong and lasting immune responses. The fundamental aim of this paper is to provide an overview of factors that affect the expression of recombinant proteins in BCG and the generation of the immune response against the target antigens, including mycobacterial promoters, location of foreign antigens, and stability of the vectors. The reporter systems that have been employed for evaluation of these molecular features in BCG are also reviewed here. [ABSTRACT FROM AUTHOR]

The extracellular-regulated kinase (ERK) 1/2 is one of the members of the mitogen-activated protein kinases (MAPKs). MAPKs are transduction proteins that play a role in controlling diverse cellular functions including proliferation and survival. In breast cancer (BC), MAPKs are involved in oestrogen receptor (ER) and HER2 pathways. This study aims to assess the biological and clinical significance of ERK1/2 protein expression in BC. Immunohistochemistry was used to assess the expression of both total (ERK1/2) and phospholyated ( p ERK1/2) ERK1/2 proteins in a large and well-characterised series of early stage BC ( n = 1300) using tissue microarray technology. ERK1/2 expression was cytoplasmic, while p-ERK1/2 was observed in the nucleus (N-p-ERK1/2) and/or cytoplasm (C-p-ERK1/2). Both ERK1/2 and p-ERK1/2 were positiviely associated with markers of good prognosis including smaller size, lower grade, expression of hormone receptor and ER-related proteins and negatively associated with HER2, HER4, KI67 and p53. Outcome analysis showed an association between N-p-ERK1/2 and better outcome. In tamoxifen-treated cases, ERK1/2 expression was an independent prognostic marker of longer survival. ERK1/2 and p-ERK1/2 were associated with good prognosis. Importantly, positivity of ERK1/2 is independently associated with better outcome in tamoxifen-treated cases. [ABSTRACT FROM AUTHOR]

This review concerns copper-containing oxidases—laccases. Principal biochemical and electrochemical properties of laccases isolated from different sources are described, as well as their structure and mechanism of catalysis. Possible applications of laccases in different fields of biotechnology are discussed. [ABSTRACT FROM AUTHOR]

The morphological diversity and dynamic aspects of presynaptic bodies are summarised. Molecular characteristics of the presynaptic machinery are discussed and the signals that control the plasticity of the presynaptic bodies are examined. A review is presented of recent findings regarding the physiology of tonically active synapses. The significance of the synaptic bodies and their dynamic changes in retinal and pineal photoreceptors are considered. [ABSTRACT FROM AUTHOR]