Metabolic profiles of Fufang Xiling Jiedu capsule in rats by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry.

Fufang Xiling Jiedu capsule (FXJC), a traditional Chinese medicine that evolved from "Yinqiao Powder", is widely used for the treatment of cold and influenza. However, due to a lack of in vivo metabolism research, the chemical components responsible for the therapeutic effects still remain unclear. Hence, this study aimed to describe the metabolic profiles of the FXJC in rat plasma, urine, and feces. A combined data mining strategy based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry was employed and 201 xenobiotics, including 117 prototype components and 84 metabolites were detected. Phenolic acids, flavonoids, triterpenes, and lignans were prominent ingredients absorbed in vivo, and the major metabolic pathways of the detected metabolites were glucuronidation, sulfation, methylation, and oxidation. This is the first systematic study on the metabolism of the FXJC in vivo, providing valuable information for future studies on the efficacy, toxicity, and mechanism of the FXJC.

Exosomal Delivery of FTO Confers Gefitinib Resistance to Recipient Cells through ABCC10 Regulation in an m6A-dependent Manner.

Gefitinib is suitable for the treatment of locally advanced or metastatic non-small cell lung cancer. However, the development of acquired resistance limits its long-term efficacy in regardless of significant clinical benefit to patients. Therefore, to elucidate the mechanism of gefitinib resistance in addition to target gene mutation may greatly increase its clinical efficacy. It was found first that N 6-methyladenosine RNA demethylase FTO was significantly enriched in serum exosomes of gefitinib-resistant (GR) patients compared with that of gefitinib-sensitive (GS) patients through exosomal RNA sequencing. Meanwhile, the average m6A proportion in GR patients was significantly lower when compared with that in GS patients. Besides, GR cell-derived exosome internalization attenuated the total m6A abundance and gefitinib sensitivity of PC9 cells. Not only FTO knockdown enhanced the gefitinib sensitivity of GR cells but also FTO reduction in donor exosomes alleviated the acquired resistance of recipient PC9 cells. GR cell-derived exosomal-FTO promoted ABCC10 of recipient cells in a m6A-dependent manner. FTO/YTHDF2/ABCC10 axis played a role in intercellular transmission of GR cell-derived exosome-mediated gefitinib resistance both in vitro and in vivo. In general, this research showed that m6A modification was involved in the decrease of gefitinib sensitivity. GR cell-derived exosomes could decrease gefitinib sensitivity of recipient cells in exosomal delivery of FTO-dependent manner. FTO/YTHDF2/ABCC10 axis played a role in intercellular transmission of GR cell-derived exosome-mediated gefitinib resistance. IMPLICATIONS: Our results elucidated another potential molecular mechanism of gefitinib resistance in non-small cell lung cancer besides secondary EGFR mutations.

Coating Cutting Blades with Thin-Film Metallic Glass to Enhance Sharpness.

In this study, we sought to enhance the cutting properties of the various blades by coating them with Zr- and Fe-based thin film metallic glasses (TFMGs) to a thickness of 234-255 nm via sputter deposition. In oil-repellency/sliding tests on kitchen blades, the sliding angle and friction forces were as follows: bare blades (31.6°) and (35 µN), Ti-coated blades (20.3°) and (23.7 µN), and Z-TFMG coated blades (16.2°) and (19.2 µN). Comparisons were conducted with bare blades and those with a Teflon coating (a low-friction material commonly used for the coating of microtome blades). We also found that the Teflon coating reduced the cutting forces of an uncoated microtome blade by ~80%, whereas the proposed Z-TFMG achieved a ~51% reduction. The Z-TFMG presented no indications of delamination after being used 30 times for cutting; however, the Teflon coating proved highly susceptible to peeling and the bare blade was affected by surface staining. These results demonstrate the efficacy of the TFMG coating in terms of low friction, non-stick performance, and substrate adhesion. The performance of Z-TFMG and F-TFMG was also evaluated in split-thickness skin graft surgery using dermatome blades aimed at elucidating the influence of TFMG coatings on the healing of surgical incisions. When tested repeatedly on hairless skin, the surface roughness of uncoated blades increased by approximately 70%, whereas the surface roughness of TFMG-coated blades increases by only 8.6%. In the presence of hair, the surface roughness of uncoated blades increased by approximately ~108%, whereas the surface roughness of TFMG-coated blades increases by only ~23%. By Day 7, the wounds produced using TFMG-coated blades were noticeably smaller than those produced using uncoated blades, and these effects were particularly evident in hairy samples. This is a clear demonstration of the efficacy of TFMG surface coatings in preserving the cutting quality of surgical instruments.