Comprehensive next-generation sequencing reveals double primary colorectal carcinoma missed by diagnostic imaging: A case report.

BACKGROUND: Multiple primary colorectal carcinoma (MPCC) is a rare clinical disease, which is challenging to differentiate from metastatic disease using histopathological methods. Next-generation sequencing (NGS) has been employed to identify multiple primary cancers. CASE SUMMARY: This study a rare case of a 63-year-old male patient diagnosed with MPCC by targeted NGS, which was initially missed by radiological evaluation. The patient was found to have two tumors located on the surface of the colorectum which had distinct genomic alterations. Based on wild-type KRAS detected in the unresected tumor, the patient benefited from the epidermal growth factor receptor (EGFR) inhibitor cetuximab treatment, but developed novel mutations including KIF5B-RET fusion, which provides a possible resistance mechanism to anti-EGFR therapy. CONCLUSION: Our case highlights the necessity of using genetic testing for primary tumor diagnosis and the application of serial plasma circulating tumor DNA profiling for dynamic disease monitoring.

Biosynthesis and evaluation of a novel highly water-soluble quercetin glycoside derivative.

Quercetin (1) was converted into quercetin 7-O-succinyl glucoside (2) by used Bacillus amyloliquefaciens FJ18 as a solvent-resistant whole-cell biocatalyst. The structure of the new compound was confirmed by LC-MS analysis and NMR spectroscopy. The water-solubility of this novel quercetin 7-O-succinyl glucoside (2) was approximately 1000 times higher than that of native quercetin (2). Quercetin (1) and quercetin 7-O-succinyl glucoside (2) exhibited significant DPPH scavenging capacity with IC50 values of 23.55 and 36.05 µM, respectively. Both compounds showed moderate cytotoxic effects against the two human cancer cell lines (MCF-7 and HepG2) with IC50 values ranging from 39.45-63.38 µM.

Design of an adjustable bipod flexure for a large-aperture mirror of a space camera.

An adjustable bipod flexure (ABF) technique for a large-aperture mirror of a space camera is presented. The proposed flexure mount can decrease the surface distortions caused by the machining error and the assembly error of the mirror assembly (MA) in a horizontal optical testing layout. Through the analysis of the compliance matrix of conventional bipod flexure, the positional relationship between the rotation center and the apex of the flexure is investigated. Then, the principle of the adjustable flexure, known as the trapezoidal switching principle, is proposed based on the analysis result. The structure and application of the flexure are also described. The optical performance of the mirror mounted by the adjustable flexures in different misalignments was performed using finite element methods. The result shows that the astigmatic aberration due to gravity is effectively reduced by adjusting the mount, and the root-mean-square value of the mirror can be minimized with the misalignment between the flexure pivot and the neutral plane minimized. New monolithic bipod flexures, based on the optimal regulating variable Δu according to the measurement results, are manufactured to replace the ABFs to secure the mirror's safety against launch loads. Modal analysis verified the mechanical safety of the MA with respect to the new monolithic flexures.

Endoplasmic reticulum stress regulates proliferation, migration and invasion of human ovarian cancer SKOV3 cells through PI3K/AKT/mTOR signaling pathway.

OBJECTIVE: The study is to explore the role of tunicamycin-induced endoplasmic reticulum stress (ERS) in human ovarian cancer (OC) SKOV3 cells proliferation, migration and invasion by modulating the activity of PI3K/AKT/mTOR pathway. METHODS: The collected human OC SKOV3 cells were randomly separated into three groups: The control group, the Tun group (treated with tunicamycin to induce ERS) and the CHOP-si group (transfected with CHOP-siRNA before tunicamycin treatment). CCK-8 method was applied for testing cell proliferation, while flow cytometry was conducted to detect cell apoptosis. Scratch test and Transwell test were used to determine the level of cell migration and invasion, respectively. Western blotting was performed to determine the related proteins expressions in ERS and PI3K/AKT/mTOR pathway. RESULTS: The cell survival rate in the Tun group was enhanced than that in the CHOP-si group, both of which were declined with the passage of time. The cell apoptosis rate in the Tun group was increased compared to the CHOP-si group, both of which were significantly elevated. The horizontal migration distance and the number of invasive cells in the Tun and CHOP-si groups were inhibited; however, the horizontal migration distance and the number of invasive cells in the CHOP-si group were enhanced than that in the Tun group. In comparison with the control group, the expressions of CHOP and TRB3 were increased in the Tun group but decreased in the CHOP-si group. The PI3K, p-AKT and p-mTOR expressions were remarkably declined in the Tun group than those in the control group (P< 0.05). CONCLUSION: The study provides strong evidence that tunicamycin-induced ERS induces the apoptosis of human OC SKOV3 cells through inhibiting PI3K/AKT/mTOR signaling pathway.