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Colorectal cancer (CRC) is a highly heterogeneous cancer and exploring novel therapeutic options is a pressing issue that needs to be addressed. Here, we established human CRC tumor-derived organoids that well represent both morphological and molecular heterogeneities of original tumors. To efficiently identify repurposed drugs for CRC, we developed a robust organoid-based drug screening system. By combining the repurposed drug library and computation-based drug prediction, 335 drugs were tested and 34 drugs with anti-CRC effects were identified. More importantly, we conducted a detailed transcriptome analysis of drug responses and divided the drug response signatures into five representative patterns: differentiation induction, growth inhibition, metabolism inhibition, immune response promotion, and cell cycle inhibition. The anticancer activities of drug candidates were further validated in the established patient-derived organoids-based xenograft (PDOX) system in vivo. We found that fedratinib, trametinib, and bortezomib exhibited effective anticancer effects. Furthermore, the concordance and discordance of drug response signatures between organoids in vitro and pairwise PDOX in vivo were evaluated. Our study offers an innovative approach for drug discovery, and the representative transcriptome features of drug responses provide valuable resources for developing novel clinical treatments for CRC. [ABSTRACT FROM AUTHOR]

Aligned discontinuous carbon fiber composites were fabricated from aligned discontinuous carbon fiber prepreg, which was prepared from continuous carbon fiber prepreg via mechanical high-frequency cutting. The internal quality and mechanical properties were characterized and compared with continuous carbon fiber composites. The results show that the internal quality of the aligned discontinuous carbon fiber composites is fine and the mechanical properties have high retention rate after the fibers were cut compared with continuous carbon fiber composites. The minimum retention rate of 0° tension strength is 63%, and the modulus is basically without chang. The minimum retention rates of 0° flexural strength and modulus are 85% and 78% respectively. The mechanical properties of aligned discontinuous carbon fiber composites are much better than that of the random oriented carbon fiber composites.

Saussurea involucrata (S. involucrata) had been reported to have anti-hepatoma function. However, the mechanism is complex and unclear. To evaluate the anti-hepatoma mechanism of S. involucrata comprehensively and make a theoretical basis for the mechanical verification of later research, we carried out this work. In this study, the total phenolic acids from S. involucrata determined by a cell suspension culture (ESPI) was mainly composed of 4,5-dicaffeoylquinic acid, according to the LC-MS analysis. BALB/c nude female mice were injected with HepG2 cells to establish an animal model of liver tumor before being divided into a control group, a low-dose group, a middle-dose group, a high-dose group, and a DDP group. Subsequently, EPSI was used as the intervention drug for mice. Biochemical indicators and differences in protein expression determined by TMT quantitative proteomics were used to resolve the mechanism after the low- (100 mg/kg), middle- (200 mg/kg), and high-dose (400 mg/kg) interventions for 24 days. The results showed that EPSI can not only limit the growth of HepG2 cells in vitro, but also can inhibit liver tumors significantly with no toxicity at high doses in vivo. Proteomics analysis revealed that the upregulated differentially expressed proteins (DE proteins) in the high-dose group were over three times that in the control group. ESPI affected the pathways significantly associated with the protein metabolic process, metabolic process, catalytic activity, hydrolase activity, proteolysis, endopeptidase activity, serine-type endopeptidase activity, etc. The treatment group showed significant differences in the pathways associated with the renin-angiotensin system, hematopoietic cell lineage, etc. In conclusion, ESPI has a significant anti-hepatoma effect and the potential mechanism was revealed. [ABSTRACT FROM AUTHOR]