Targeted therapy via the patient-friendly oral route remains the holy grail of chemotherapy for cancer. Herein we report a yeast-derived platform for targeted oral delivery of cisplatin (CDDP) that is one of the most effective drugs for chemotherapy of various types of cancers.

Liver metastasis is the major reason for most of colorectal cancer (CRC) related deaths. Accumulating evidence indicates that CRC patients with non-alcoholic fatty liver disease (NAFLD) are at a greater risk of developing liver metastasis. With the growing prevalence of NAFLD, a better understanding of the molecular mechanism in NAFLD-driven CRC liver metastasis is needed. In this study, we demonstrated that NAFLD facilitated CRC liver metastasis as a metabolic disorder and promoted the stemness of metastatic CRC cells for their colonization and outgrowth in hepatic niches. Metabolically, the lipid-rich microenvironment in NAFLD activated de novo palmitate biosynthesis in metastatic CRC cells via upregulating fatty acid synthase (FASN). Moreover, increased intracellular palmitate bioavailability promoted EGFR palmitoylation to enhance its protein stability and plasma membrane localization. Furthermore, we demonstrated that the FDA-approved FASN inhibitor orlistat could reduce NAFLD-activated endogenous palmitate production, thus inhibiting palmitoylation of EGFR to suppress CRC cell stemness and restrict liver metastasis in synergy with conventional chemotherapy. These findings reveal that the NAFLD metabolic microenvironment boosts endogenous palmitate biosynthesis in metastatic CRC cells and promotes cell stemness via EGFR palmitoylation, and FASN inhibitor orlistat could be a candidate adjuvant drug to suppress liver metastasis in CRC patients with NAFLD.

Although chemotherapy represents a predominant anti-cancer therapeutic modality, drug treatment efficacy is often limited due to the development of resistant tumor cells. The pregnane X receptor (PXR) affects chemotherapeutic effects by regulating targets involved in drug metabolism and transportation, but the regulatory mechanism is poorly understood. Oxaliplatin (L-OHP) content in tumor cells was analyzed by mass cytometry. The roles of PXR on cancer cell proliferation, apoptosis and tumor growth with L-OHP-treated were investigated by MTS, colony formation, flow cytometry and xenograft tumor assays. Luciferase reporter, Chromatin-immunoprecipitation and Site-directed mutagenesis were evaluated the mechanisms. The PXR and multidrug resistance-related protein 3 (MRP3) expressions were examined by western blot, RT-PCR or immunohistochemistry of TMA. Kaplan-Meier and Cox regression were adopted to analyze the prognostic value of PXR in colorectal cancer (CRC). PXR over-expression significantly increased oxaliplatin (L-OHP) transport capacity with a reduction of its content and repressed the effects of L-OHP on tumour cell proliferation and apoptosis. Conversely, PXR knockdown augments L-OHP-mediated cellular proliferation and apoptosis. Moreover, PXR significantly reduced the therapeutic effects of L-OHP on tumor growth in nude mice. Further studies indicated a positive correlation between PXR and MRP3 expression and this finding was confirmed in two independent cohorts. Significantly increased MRP3 expression was also found in PXR over-expressing cell lines. Mechanistically, PXR could directly bind to the MRP3 promoter, activating its transcription. The PXR binding sites were determined to be at -796 to -782bp (CTGAAGCAGAGGGAA) and the key binding sites were the “AGGGA” (-787 to -783bp) on the MRP3 promoter. Accordingly, blockade of MRP3 diminishes the effects on drug resistance of PXR. In addition, PXR expression is significantly associated with poor overall survival and represents an unfavorable and independent factor for male or stage I + II CRC patient prognosis. PXR is a potential biomarker for predicting outcome and activates MRP3 transcription by directly binding to its promoter resulting in an increased L-OHP efflux capacity, and resistance to L-OHP or platinum drugs in CRC. Our work reveals a novel and unique mechanism of drug resistance in CRC.

Lonicera japonica Thunb., known as Japanese honeysuckle or golden-and-silver honeysuckle, belongs to the honeysuckle family and is native to eastern Asia, including China, Japan, and Korea. Microscopy, spectrophotometry, colorimetry, and the Royal Horticulture Society of Colorimetric Card (RHSCC) were used to compare and analyze the pigment distribution, content, and color variations in the Yujin 2 and Damaohua cultivars at different developmental stages. There were notable differences in the corolla color and the cross-section color between different developmental stages and different varieties. The lightness (L*), redness (a*), and yellowness (b*) values were calculated for each period for the two cultivars to observe variation trends. The chlorophyll content in the corollas of both cultivars showed declining trends with different rates. The chlorophyll content decreased rapidly from the young period to the two white period, and changed gradually from the two white period to the golden period. Moreover, the carotenoid content declined slightly from the young period to the silver period and rose sharply during the golden period. The ratio of these two pigment contents increased dramatically during the golden period: by 11.51 and 6.53 times in ‘Yujin 2’ and ‘Damaohua’, respectively. There were significant differences in corolla color, cross-section color, and the content of three pigments between the two varieties of honeysuckle. distribution and variation of pigments were the key factors affecting the flower color of honeysuckle. This study provides a basis for the identification and breeding of honeysuckle varieties and lays a foundation for further studies on the function and molecular mechanisms of pigments.

Background: Gleditsia sinensis Lam. (Leguminosae), a dioecious perennial arbor, demonstrates important medicinal properties and economic value. These properties can be harnessed depending on the sex of the plant. However, the sex of the plants is difficult to identify accurately through morphological methods before the flowering. Results: We used bulked segregant analysis to screen sex-specific simple sequence repeat (SSR) markers in G. sinensis. Five male and five female plants were pooled to form the male and female bulks, respectively, and subjected to whole-genome sequencing. After high-throughput sequencing, 5,350,359 sequences were obtained, in which 2,065,210 SSRs were searched. Among them, the number of duplicated SSRs was the highest. The male plants could reach 857,874, which accounted for 60.86% of the total number of male plants. The female plants could reach 1,447,603, which accounted for 56.25% of the total model of the female plants. Among all the nucleotide repeat types, the A/T-rich motif was the most abundant. A total of 309,516 female strain-specific SSRs were selected by clustering. After designing the primers, the male and female gene pools were amplified, and five pairs of primers (i.e., 27, 34, 36, 39, and 41) were found to amplify the differential bands in the male and female gene pools. Using the five pairs of primers, we performed PCR verification on 10 individuals of known sex, which constructed the gene pool. The female plants amplified a single fragment of lengths (i.e., 186, 305, 266, 203, and 260 bp) and no male plant strip, thereby completing the identification of the male and female sexes of the G. sinensis. Conclusions: This study provides accurate sex identification strategies between female and male plants, thus improving the utilization rate of G. sinensis resources.