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Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide, particularly in Asian populations, and responds poorly to conventional therapy. Subclassification of ESCCs by molecular analysis is a powerful strategy in extending conventional clinicopathologic classification, improving prognosis and therapy. Here we identified two ESCC molecular subtypes in Chinese population using gene expression profiling data and further validated the molecular subtypes in two other independent Asian populations (Japanese and Vietnamese). Subtype I ESCCs were enriched in pathways including immune response, while genes overexpressed in subtype II ESCCs were mainly involved in ectoderm development, glycolysis process, and cell proliferation. Specifically, we identified potential ESCC subtype-specific diagnostic markers (FOXA1 and EYA2 for subtype I, LAMC2 and KRT14 for subtype II) and further validated them in a fourth Asian cohort. In addition, we propose a few subtype-specific therapeutic targets for ESCC, which may guide future ESCC clinical treatment when further validated.

Βeta-cyclodextrin (β-CD) with a hydrophobic cavity enables the formation of inclusion complexes with organic molecules. The formation of host–guest complexes makes the application of β-CD popular in many fields, but their interaction with organisms is poorly understood. In the present study, the effect of β-CD on gut microbiota (16S rRNA gene sequencing), serum metabolites (gas chromatography–mass spectrometry platform), and their correlation (Pearson correlation analysis) was investigated after 14 days repeated oral exposure in mice. β-CD did not significantly affect the α-diversity indexes, including Richness, Chao1, Shannon and Simpson indexes, but disturbed the structure of the gut bacteria according to the result of principal component analysis (PCA). After taxonomic assignment, 1 in 27 phyla, 2 in 48 classes, 3 in 107 orders, 6 in 192 families, and 8 in 332 genera were significantly different between control and β-CD treated groups. The serum metabolites were significantly changed after β-CD treatment according to the result of unsupervized PCA and supervised partial least squares-discriminant analysis (PLS-DA). A total of 112 differential metabolites (89 downregulated and 23 upregulated) were identified based on the VIP >1 from orthogonal PLS-DA and p

Enzyme-like catalysis is the use of artificial catalysts to catalyze chemical reactions, which has the characteristics of enzymatic catalysis, such as high selectivity, high efficiency, and mild reaction conditions. In recent years, 2D materials, thickness ranging from a single to several atomic layers, have become a hot research topic in the field of materials, while 2D materials happen to have enzyme-like catalysis property. Among them, 2H-MoS[subscript 2] is easy to peel away to form the 2D structure due to covalent bonds between S-Mo-Sin each layer and van der Waals forces between layers. Meanwhile, using a mechanical solid-phase chemical method to produce its S defect, the S defect can significantly improve the catalytic efficiency and achieve rapid catalytic oxidation of TMB (3,3,5,5-tetramethylbenzidine) for quantitative detection of trace ascorbic acid. The experiment described in this study is designed for senior undergraduates majoring in chemistry, materials, chemical engineering, catalysis, etc., as part of their training in comprehensive chemical experimentation. This experiment can introduce students to the synthesis of 2D materials, enzyme-like catalytic reactions, and the principles for the use of analytical instruments. Integrating this experiment into undergraduate teaching will (1) stimulate students to think about developing innovative detection methods answering to actual scientific and social needs; (2) familiarize the students with serious and rigorous scientific method through the process of exploring and optimizing detection methods; and (3) increase students' understanding of catalytic analysis and detection through exploration of innovative detection methods, thereby raising their practical skills to a high-level.

Heat shock factor 1 (Hsf1) serves an important role in regulating the proliferation of human tumor cell lines in vitro and tissue specific tumorigenesis in certain mouse models. However, its role in viral-oncogenesis remains to be fully elucidated. In the current study, the role of Hsf1 in fibroblastoma derived from simian virus 40/T antigen (SV40/TAG)-transformed mouse embryonic fibroblast (MEF) cell lines was investigated. Knockout of Hsf1 inhibited MEF cell proliferation in vitro and fibroblastoma growth and metastasis to the lungs in vivo in nude mice. Knockout of Hsf1 increased the protein expression levels of p53 and phosphorylated retinoblastoma protein (pRb), however reduced the expression of heat shock protein 25 (Hsp25) in addition to the expression of the angiogenesis markers vascular endothelial growth factor, cluster of differentiation 34 and factor VIII related antigen. Furthermore, immunoprecipitation indicated that knockout of Hsf1 inhibited the association between SV40/TAG and p53 or pRb. These data suggest that Hsf1 is involved in the regulation of SV40/TAG-derived fibroblastoma growth and metastasis by modulating the association between SV40/TAG and tumor suppressor p53 and pRb. The current study provides further evidence that Hsf1 may be a novel therapeutic target in the treatment of cancer. [ABSTRACT FROM AUTHOR]

Heat shock factor 1 (HSF1), a main regulator of the heat shock response in eukaryotes, increases cell survival in numerous pathophysiological conditions. The aim of the present study was to o bserve the function of defective HSF1 expression in HEK293T cells. shRNA of human HSF1 was constructed into the retroviral vector pLTHR generating pLTHR-shRNA-HSF1. The shRNA was transiently transfected into HEK293T cells to silence the expression of the HSF1 gene. Cell colony formation, MTT and cell cycle assays were used to analyze the SV40 T-antigen (Ag)-transformed cell proliferation rate. Immunoblotting was used to study the protein expression of HSF1, SV40 T-Ag, p53, p21, heat shock protein 90 (Hsp90), Hsp70 and Hsp25. The results revealed that a deficiency in HSF1 expression inhibited cellular growth. Defective HSF1 upregulated the protein expression of p53, retinoblastoma protein (Rb) and SV40 T-Ag, and reduced the association between SV40 T-Ag and p53/Rb, which resulted in growth inhibition of SV40 T-Ag-transformed cells. In conclusion, HSF1 is involved in the regulation of SV40 T-Ag-induced cell growth and modulates the expression of p53 and Rb proteins. [ABSTRACT FROM AUTHOR]

Aims: The prenatal ethanol exposure induced neuroapoptosis and neuron loss in visual cortex would be investigated in mice at P0, P7 and P14. Methods: Intubating pregnant mice ethanol daily began on E5 and continued through the pup's birth. The neuroapoptosis in visual cortex was visualized by the caspase 3 immunocytochemistry, and the neuron loss was observed with Nissl method as well. Results: With prenatal ethanol exposure, the dose-dependent neuroapoptosis and neuron loss in visual cortex could be found at P0 and even at P7 and P14 as well. Conclusions: The prenatal ethanol exposure induced neuroapoptosis and neuron loss will persist into postnatal stage, and the long-term effect of neuroapoptosis might be one of the causes of postnatal neurobehavioural disturbances associated with fetal alcohol syndrome. [ABSTRACT FROM AUTHOR]

The article discusses a study on how the mouse cerebellar cortex develops. The study sought to determine the formation of the layered structure of a cerebellum that is about to develop. It involved a total of 90 adult female and male mice raised in the same cage. The time of pregnancy of the female mice and their embryonic day were recorded as part of the study. At embryonic day 12, the cerebellum's primordium comprised the ependymal, mantle and marginal layers. The role of apoptosis and neurogenesis are also discussed.