ANOS1 accelerates the progression of esophageal cancer identified by multi-omic approaches.

To assess the role of ANOS1 in esophageal cancer (ESCA) progression, multi-omic analysis and experimental validation were employed. It was revealed that ANOS1 expression is significantly enhanced in ESCA patients and cell lines. The expression level of ANOS1 in ESCA patients can distinguish the malignancy from normal tissue with an area under curve (AUC) >0.75. Moreover, increased expression of ANOS1 is associated with advanced T stage and worse disease-free survival of ESCA patients. Therefore, a clinically applicable nomogram with ANOS1 was established with strong predictive power. Furthermore, high expression of ANOS1 in ESCA is correlated with (i) the enrichment of epithelial-mesenchymal transition by gene set enrichment analysis, (ii) the involvement in hypoxia, angiogenesis, WNT signaling pathway, and TGFß signaling pathway by gene set variation analysis, (iii) the presence of the small insertion and deletion mutational signature ID9, associated with chromothripsis, in the single-nucleotide polymorphism analysis, (iv) the amplification of 11q13.3 in the copy number variants analysis, (v) the enrichment of cancer-associated fibroblasts and mesenchymal stromal cells in the tumor microenvironment. All the results from multi-omic analysis indicate that ANOS1 plays a pivotal role in accelerating the progression of ESCA. Results from in vivo and in vitro experiments show that the knockdown of ANOS1 hampers the proliferation of ESCA cells, further validating the oncogenic role of ANOS1 in ESCA. Additionally, potential chemotherapeutics with sensitivity were identified in the high-ANOS1 group. In conclusion, ANOS1 accelerates the progression of ESCA.

Buckling behavior of ternary one-dimensional van der Waals heterostructures.

One-dimensional van der Waals heterostructures (1D vdWHs) may suffer from external compression when applied in field-effect, light-emitting and photovoltaic devices. Ternary 1D vdWHs were recently reported to be successfully synthesized (Xianget al2020Science367, 537). In present work, the buckling behavior of ternary 1D vdWH consisting of an inner carbon nanotube, a middle boron nitride nanotube and an outer molybdenum disulfide nanotube is extensively investigated by using molecular dynamics simulations. We find that the composite can effectively enhance the capability of axial compression of the inner nanotubes. The 1D vdWH gradually loses its stability under uniaxial compression and the critical stress of buckling decreases as the temperature increases. Slenderness ratioαof 4.8 ≤α≤ 7.2 has a slight influence on the strength and stability of ternary 1D vdWH under axial compression. To obtain a 1D vdWH with best compressive stability and strength, there is an optimal diameter existing for any specific length. Our work provides guidance for the design of 1D vdWH with desired compressive stability.

FMS-Related Tyrosine Kinase 3 Ligand Promotes Radioresistance in Esophageal Squamous Cell Carcinoma.

Aim: The FMS-related tyrosine kinase 3 ligand (FL) has an important role in regulating FMS-related tyrosine kinase 3 (Flt-3) activity. Serum FL levels are markedly increased among patients with hematopoietic disease. However, its role in radiation treatment remains unclear. In this study, we investigated the effects of FL on radiotherapy for esophageal squamous cell carcinoma (ESCC). Methods: KYSE150 and KYSE450 cells were stimulated with FL (200 ng/ml). mRNA expression was analyzed using qRT-PCR. Cell viability was checked using CCK-8 assay kits. Proliferation was determined using the EdU assay. Radiosensitivity was detected through a colony-forming assay. Flow cytometry was used to evaluate cell apoptosis. The number of γH2AX foci was verified using an immunofluorescence assay. The change in relative proteins was determined by western blot analysis. The growth of transplanted tumors was demonstrated in nude mice. Results: Our results showed that FL increased the radiation resistance of ESCC cells by promoting clone formation, increasing EdU incorporation, enhancing DNA damage repair, and inhibiting apoptosis. Moreover, the Flt-3 receptor expression significantly increased in ESCC cells after radiation, which may have been an important factor in their radioresistance. Conclusion: Our results suggest that FL increases the radioresistance of esophageal cancer cells and that FL-Flt-3 could be a potential target for enhancing radiosensitivity in ESCC.

Organocatalytic C3-functionalization of indolizines: synthesis of biologically important indolizine derivatives.

A Brønsted acid-catalyzed C3-alkylation of indolizines has been established with different electrophiles such as ortho-hydroxybenzyl alcohols, other precursors of para-quinone methides and ortho-quinone methides, and 2-indolylmethanol as well. By using this approach, a series of C3-functionalized indolizines were synthesized in overall good yields (up to 89%). These examples demonstrate that the Brønsted acid-catalyzed C3-alkylation of indolizines has a wide applicability, which can serve as a useful method for synthesizing C3-functionalized indolizine derivatives with structural diversity. This reaction has fulfilled the task of developing organocatalytic C3-functionalization of indolizines for the synthesis of biologically important indolizine derivatives.