Pancreatic cancer (PC) is one of the most lethal cancers known worldwide, and its prognosis is poor in most patients. Exosomes are nanosized extracellular vesicles, which are released from various ...cell types. They are involved in cellular communication. The diagnosis and treatment of PC were improved substantially with exosomes. In this study, we isolated PC‐derived exosomes and investigated their proteomic profile. Then, we conducted bioinformatic analysis on proteomic data. Differential ultracentrifugation was performed to isolate exosomes from human serum samples and four PC cell lines. Transmission electron microscopy and Western blot analysis were used to characterize the isolated exosomes. Liquid chromatography coupled with tandem mass spectrometry was conducted to identify the proteome of serum exosomes. Proteomic analysis demonstrated that all the serum exosomes were derived from three cohorts of human subjects; these serum exosomes contained a total of 655 proteins, out of which 315 proteins overlapped with ExoCarta database. Gene oncology and kyoto encyclopedia of genes and genomes analyses provided the functional annotation of the proteome. Interestingly, 18 or 14 proteins were upregulated and 11 or 14 proteins were downregulated in serum exosomes derived from patients with PC as compared with in serum exosomes derived from healthy volunteers or from pancreatitis patients respectively. Annexin A11, a calcium‐dependent phospholipid‐binding protein, was expressed in a PC cell line (CFPAC‐1)‐derived exosomes and in tumor tissues of patients with PC, respectively. Our data provided a basic foundation for further studies on the protein composition of PC‐derived exosomes and its involvement in PC biology.
AIMS: The influence of bacterial species/strains in agitated culture was investigated on the morphology and structure characteristics of bacterial cellulose. METHODS AND RESULTS: Komagataeibacter ...nataicola Y19 and Gluconacetobacter entanii ACCC10215 were inoculated in Hestrin–Schramm (HS) medium and subjected to agitated cultivation. Different kinds of BCs were obtained including flocky asterisk‐like BC by G. entanii ACCC10215 and solid sphere‐like BC by K. nataicola Y19. The SEM results showed that the asterisk‐like BC had larger pores than the solid sphere‐like BC. The FT‐IR and X‐ray diffraction results showed the asterisk‐like BC had lower crystallinity (81·43%), higher cellulose Iα mass fraction (79·74%) and smaller crystallite size. CONCLUSIONS: The different species/strains can influence the morphology and structure characteristics of BC in agitated culture. SIGNIFICANCE AND IMPACT OF THE STUDY: We examined the influence of different species/strains on the morphology, macro‐ and microstructure of BCs produced in agitated culture for the first time, which suggest that different BCs with potential applications could be obtained by choosing different species or strains and fermentation method.
Recent clinical successes of cancer immunotherapy necessitate the investigation of the interaction between malignant cells and the host immune system. However, elucidation of complex tumor-immune ...interactions presents major computational and experimental challenges. Here, we present Tumor Immune Estimation Resource (TIMER; cistrome.shinyapps.io/timer) to comprehensively investigate molecular characterization of tumor-immune interactions. Levels of six tumor-infiltrating immune subsets are precalculated for 10,897 tumors from 32 cancer types. TIMER provides 6 major analytic modules that allow users to interactively explore the associations between immune infiltrates and a wide spectrum of factors, including gene expression, clinical outcomes, somatic mutations, and somatic copy number alterations. TIMER provides a user-friendly web interface for dynamic analysis and visualization of these associations, which will be of broad utilities to cancer researchers.
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Background
The expression of chronic rhinosinusitis (CRS) is multidimensional. Disease heterogeneity in patients with CRS remains poorly understood. This study aimed to identify endotypes of CRS ...using cluster analysis by integrating multidimensional characteristics and to explore their association with treatment outcomes.
Methods
A total of 28 clinical variables and 39 mucosal cellular and molecular variables were analyzed using principal component analysis. Cluster analysis was performed on 246 prospectively recruited Chinese CRS patients with at least 1‐year postoperative follow‐up. Difficult‐to‐treat CRS was characterized in each generated cluster.
Results
Seven subject clusters were identified. Cluster 1 (13.01%) was comparable to the classic well‐defined eosinophilic CRS with polyps, having severe disease and the highest proportion of difficult‐to‐treat CRS. Patients in cluster 2 (16.26%) and cluster 4 (13.82%) had relatively lower proportions of presence of polyps and presented mild inflammation with moderate proportions of difficult‐to‐treat cases. Subjects in cluster 2 were highly atopic. Cluster 3 (7.31%) and cluster 6 (21.14%) were characterized by severe or moderate neutrophilic inflammation, respectively, and with elevated levels of IL‐8 and high proportions of difficult‐to‐treat CRS. Cluster 5 (4.07%) was a unique group characterized by the highest levels of IL‐10 and lacked difficult‐to‐treat cases. Cluster 7 (24.39%) demonstrated the lowest symptom severity, a low proportion of difficult‐to‐treat CRS, and low inflammation load. Finally, we found that difficult‐to‐treat CRS was associated with distinct clinical features and biomarkers in the different clusters.
Conclusions
Distinct clinicopathobiologic clusters of CRS display differences in clinical response to treatments and characteristics of difficult‐to‐treat CRS.
The long noncoding RNA TINCR shows aberrant expression in human squamous carcinomas. However, its expression and function in gastric cancer remain unclear. We report that TINCR is strongly ...upregulated in human gastric carcinoma (GC), where it was found to contribute to oncogenesis and cancer progression. We also revealed that TINCR overexpression is induced by nuclear transcription factor SP1. Silencing TINCR expression inhibited cell proliferation, colony formation, tumorigenicity and apoptosis promotion, whereas TINCR overexpression promoted cell growth, as documented in the SGC7901 and BGC823 cell lines. Mechanistic analyses indicated that TINCR could bind to STAU1 (staufen1) protein, and influence KLF2 mRNA stability and expression, then KLF2 regulated cyclin-dependent kinase genes CDKN1A/P21 and CDKN2B/P15 transcription and expression, thereby affecting the proliferation and apoptosis of GC cells. Together, our findings suggest that TINCR contributes to the oncogenic potential of GC and may constitute a potential therapeutic target in this disease.
We report that the classical phenomenon of optical activity, which is traditionally associated with chirality (helicity) of organic molecules, proteins, and inorganic structures, can be observed in ...artificial planar media which exhibit neither 3D nor 2D chirality. We observe the effect in the microwave and optical parts of the spectrum at oblique incidence to regular arrays of nonchiral subwavelength metamolecules in the form of strong circular dichroism and birefringence indistinguishable from those of chiral three-dimensional media.
•Propose a multi-stage optimal control problem to minimize vehicle fuel consumption.•Consider the impacts from queue on the optimal vehicle speed trajectory.•Develop a constrained optimization model ...to solve the problem efficiently.
Vehicle speed trajectory significantly impacts fuel consumption and greenhouse gas emissions, especially for trips on signalized arterials. Although a large amount of research has been conducted aiming at providing optimal speed advisory to drivers, impacts from queues at intersections are not considered. Ignoring the constraints induced by queues could result in suboptimal or infeasible solutions. In this study, a multi-stage optimal control formulation is proposed to obtain the optimal vehicle trajectory on signalized arterials, where both vehicle queue and traffic light status are considered. To facilitate the real-time update of the optimal speed trajectory, a constrained optimization model is proposed as an approximation approach, which can be solved much quicker. Numerical examples demonstrate the effectiveness of the proposed optimal control model and the solution efficiency of the proposed approach.
Families and genera assigned to Tremellomycetes have been mainly circumscribed by morphology and for the yeasts also by biochemical and physiological characteristics. This phenotype-based ...classification is largely in conflict with molecular phylogenetic analyses. Here a phylogenetic classification framework for the Tremellomycetes is proposed based on the results of phylogenetic analyses from a seven-genes dataset covering the majority of tremellomycetous yeasts and closely related filamentous taxa. Circumscriptions of the taxonomic units at the order, family and genus levels recognised were quantitatively assessed using the phylogenetic rank boundary optimisation (PRBO) and modified general mixed Yule coalescent (GMYC) tests. In addition, a comprehensive phylogenetic analysis on an expanded LSU rRNA (D1/D2 domains) gene sequence dataset covering as many as available teleomorphic and filamentous taxa within Tremellomycetes was performed to investigate the relationships between yeasts and filamentous taxa and to examine the stability of undersampled clades. Based on the results inferred from molecular data and morphological and physiochemical features, we propose an updated classification for the Tremellomycetes. We accept five orders, 17 families and 54 genera, including seven new families and 18 new genera. In addition, seven families and 17 genera are emended and one new species name and 185 new combinations are proposed. We propose to use the term pro tempore or pro tem. in abbreviation to indicate the species names that are temporarily maintained.
Abstract
The Cistrome Data Browser (DB) is a resource of human and mouse cis-regulatory information derived from ChIP-seq, DNase-seq and ATAC-seq chromatin profiling assays, which map the genome-wide ...locations of transcription factor binding sites, histone post-translational modifications and regions of chromatin accessible to endonuclease activity. Currently, the Cistrome DB contains approximately 47,000 human and mouse samples with about 24,000 newly collected datasets compared to the previous release two years ago. Furthermore, the Cistrome DB has a new Toolkit module with several features that allow users to better utilize the large-scale ChIP-seq, DNase-seq, and ATAC-seq data. First, users can query the factors which are likely to regulate a specific gene of interest. Second, the Cistrome DB Toolkit facilitates searches for factor binding, histone modifications, and chromatin accessibility in any given genomic interval shorter than 2Mb. Third, the Toolkit can determine the most similar ChIP-seq, DNase-seq, and ATAC-seq samples in terms of genomic interval overlaps with user-provided genomic interval sets. The Cistrome DB is a user-friendly, up-to-date, and well maintained resource, and the new tools will greatly benefit the biomedical research community. The database is freely available at http://cistrome.org/db, and the Toolkit is at http://dbtoolkit.cistrome.org.