Coumestrol facilitates apoptosis in colorectal cancer cells by interacting with ZIP8 protein via the ferroptosis pathway.

Objective: So far, there have been no reports of coumestrol inhibiting colorectal cancer (CRC) through the ferroptosis pathway. This study is to investigate the mechanism of the traditional Chinese medicine monomer coumestrol in the treatment of CRC. Methods: Data on CRC transcriptome sequencing was obtained from the GEO database and TCGA database. Bioinformatics analyses were conducted to screen for CRC prognostic-related key genes and their potential binding monomers in traditional Chinese medicine. The inhibitory effect of coumestrol on CRC cell lines (COLO 205 & HCT 116) was determined using the CCK-8 assay, and cell apoptosis was assessed by flow cytometry. The content of ferrous ions was measured using the Ferrous Ion Content Assay Kit. The expression of ferroptosis pathway-related genes SLC39A8, NCOA4, VDAC2, and NOX2 before and after small interference RNA (siRNA) was examined through real-time PCR and Western blotting. Results: SLC39A8 was found to be associated with CRC clinical progression staging, and its encoded protein ZIP8 may bind to coumestrol. KEGG enrichment analysis suggested that ZIP8 plays a role in iron transmembrane transport and may affect the expression of ferroptosis pathway-related genes NCOA4, VDAC2, and NOX2. Coumestrol was found to induce apoptosis in CRC cell lines by upregulating the expression of ferroptosis pathway-related genes SLC39A8, NCOA4, VDAC2, and NOX2. However, coumestrol was unable to upregulate the expression of ferroptosis pathway-related genes in CRC cell lines after SLC39A8 interference. Conclusion: Coumestrol facilitates apoptosis in CRC cells by interacting with ZIP8 protein via the ferroptosis pathway.

Value of intralesional and perilesional radiomics for predicting the bioactivity of hepatic alveolar echinococcosis.

Objectives: To investigate the value of intralesional and perilesional radiomics based on computed tomography (CT) in predicting the bioactivity of hepatic alveolar echinococcosis (HAE). Materials and methods: In this retrospective study, 131 patients who underwent surgical resection and diagnosed HAE in pathology were included (bioactive, n=69; bioinactive, n=62). All patients were randomly assigned to the training cohort (n=78) and validation cohort (n=53) in a 6:4 ratio. The gross lesion volume (GLV), perilesional volume (PLV), and gross combined perilesional volume (GPLV) radiomics features were extracted on CT images of portal vein phase. Feature selection was performed by intra-class correlation coefficient (ICC), univariate analysis, and least absolute shrinkage and selection operator (LASSO). Radiomics models were established by support vector machine (SVM). The Radscore of the best radiomics model and clinical independent predictors were combined to establish a clinical radiomics nomogram. Receiver operating characteristic curve (ROC) and decision curves were used to evaluate the predictive performance of the nomogram model. Results: In the training cohort, the area under the ROC curve (AUC) of the GLV, PLV, and GPLV radiomic models was 0.774, 0.729, and 0.868, respectively. GPLV radiomic models performed best among the three models in training and validation cohort. Calcification type and fibrinogen were clinical independent predictors (p<0.05). The AUC of the nomogram-model-based clinical and GPLV radiomic signatures was 0.914 in the training cohort and 0.833 in the validation cohort. The decision curve analysis showed that the nomogram had greater benefits compared with the single radiomics model or clinical model. Conclusion: The nomogram model based on clinical and GPLV radiomic signatures shows the best performance in prediction of the bioactivity of HAE. Radiomics including perilesional tissue can significantly improve the prediction efficacy of HAE bioactivity.

Causal role of immune cells on cervical cancer onset revealed by two-sample Mendelian randomization study.

Cervical cancer (CC) is a prevalent gynecological cancer worldwide that significantly impacts the quality of life and the physical and mental well-being of women. However, there have been limited studies utilizing Mendelian randomization (MR) analysis to investigate the connection between immune cells and CC. This study is to investigate the causal effects of immune traits on CC and non-neoplastic conditions of the cervix. The GWAS data for 731 immunophenotypes and six GWAS data for CC from the FinnGen database were downloaded. Subsequently, a two-sample MR analysis was conducted using the MR Egger, Weighted median, Inverse variance weighted (IVW), Simple mode, and Weighted mode methods. Our study has identified the potential causal effects of immune traits on inflammatory diseases of the cervix, other noninflammatory disorders of the cervix uteri, carcinoma in situ of cervix uteri, adenocarcinomas of cervix, squamous cell neoplasms and carcinoma of cervix, as well as malignant neoplasm of the cervix uteri, with the respective numbers being 8, 6, 11, 8, 23, and 12, respectively. A strong correlation between classic monocytes and various cervical diseases was revealed. Furthermore, we discovered that B cells expressing BAFF-R have the ability to impede the advancement of malignant CC, specifically squamous cell neoplasms and carcinoma of cervix. Our study has demonstrated a significant association between immune traits and both CC and non-neoplastic conditions of the cervix through two-sample Mendelian randomization, providing valuable insights for future clinical research.

Icaritin Derivative IC2 Induces Cytoprotective Autophagy of Breast Cancer Cells via SCD1 Inhibition.

Breast cancer is one of the most prevalent malignancies and the leading cause of cancer-associated mortality in China. Icaritin (ICT), a prenyl flavonoid derived from the Epimedium Genus, has been proven to inhibit the proliferation and stemness of breast cancer cells. Our previous study demonstrated that IC2, a derivative of ICT, could induce breast cancer cell apoptosis by Stearoyl-CoA desaturase 1 (SCD1) inhibition. The present study further investigated the mechanism of the inhibitory effects of IC2 on breast cancer cells in vitro and in vivo. Our results proved that IC2 could stimulate autophagy in breast cancer cells with the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling and mitogen-activated protein kinase (MAPK) signaling. Combination treatment of the AMPK inhibitor decreased IC2-induced autophagy while it markedly enhanced IC2-induced apoptosis. In common with IC2-induced apoptosis, SCD1 overexpression or the addition of exogenous oleic acid (OA) could also alleviate IC2-induced autophagy. In vivo assays additionally demonstrated that IC2 treatment markedly inhibited tumor growth in a mouse breast cancer xenograft model. Overall, our study was the first to demonstrate that IC2 induced cytoprotective autophagy by SCD1 inhibition in breast cancer cells and that the autophagy inhibitor markedly enhanced the anticancer activity of IC2. Therefore, IC2 was a potential candidate compound in combination therapy for breast cancer.

Synthesis and characterization of tung oil-based UV curable for three-dimensional printing resins.

Using tung oil as the raw material, a new bio-based prepolymer was successfully synthesized by reacting with acrylic-modified rosin (ß-acryloyl nutrient ethyl) ester (ARA)/acrylic-2-hydroxyethyl ester (HEA) followed by the use of the above composite material as the matrix and then reacting with the active diluent (2-HEMA, TPGDA) and the photoinitiator TPO and Irgacure1173 to successfully synthesize a new type of bio-based prepolymer-acrylate-epoxy tung oil polypolymer (AETP). The tung oil monomer before and after the epoxy formation was compared by proton NMR spectroscopy, and the chemical structure of AETP was analyzed by Fourier transform spectroscopy. Tung oil has an acid value of 1.5 mg KOH per g, an epoxy value of 5.38%, an iodine value of 11.28 g/100 g, and a refractive index of n 25 = 1.475. Composite-based 3D printing resins (like AETP) were cured using digital light treatment, while some samples were also post-treated via ultraviolet (UV) light treatment. The AETP-based 3D printing resin has excellent thermal and mechanical properties, and the viscosity of its system is 313 mPa s; exposure time 4.5 s; the tensile strength, flexural strength and flexural modulus were 62 MPA, 63.84 MPa and 916.708 MPa, respectively; Shore hardness was 80 HD and shrinkage was 4.00%. The good performance of the AETP-based 3D printing resin is attributed to the rigidity of their tightly crosslinked structure. This study pioneered a method for producing photoactive acrylates (e.g., tung oil-based acrylate oligomer resins) from renewable, low-cost biomass for light-curing 3D printing.

Comparative genome anatomy reveals evolutionary insights into a unique amphitriploid fish.

Triploids are rare in nature because of difficulties in meiotic and gametogenic processes, especially in vertebrates. The Carassius complex of cyprinid teleosts contains sexual tetraploid crucian carp/goldfish (C. auratus) and unisexual hexaploid gibel carp/Prussian carp (C. gibelio) lineages, providing a valuable model for studying the evolution and maintenance mechanism of unisexual polyploids in vertebrates. Here we sequence the genomes of the two species and assemble their haplotypes, which contain two subgenomes (A and B), to the chromosome level. Sequencing coverage analysis reveals that C. gibelio is an amphitriploid (AAABBB) with two triploid sets of chromosomes; each set is derived from a different ancestor. Resequencing data from different strains of C. gibelio show that unisexual reproduction has been maintained for over 0.82 million years. Comparative genomics show intensive expansion and alterations of meiotic cell cycle-related genes and an oocyte-specific histone variant. Cytological assays indicate that C. gibelio produces unreduced oocytes by an alternative ameiotic pathway; however, sporadic homologous recombination and a high rate of gene conversion also exist in C. gibelio. These genomic changes might have facilitated purging deleterious mutations and maintaining genome stability in this unisexual amphitriploid fish. Overall, the current results provide novel insights into the evolutionary mechanisms of the reproductive success in unisexual polyploid vertebrates.

Identifying Actionable Variants Using Capture-Based Targeted Sequencing in 563 Patients With Non-Small Cell Lung Carcinoma.

Although the NSCLC diagnostic standards recommend the detection of driver gene mutation, comprehensive genomic profiling has not been used widely in clinical practice. As to the different mutation spectrum characteristics between populations, the research based on Chinese NSCLC cohort is very important for clinical practice. Therefore, we collected 563 surgical specimens from patients with non-small cell lung carcinoma and applied capture-based sequencing using eight-gene panel. We identified 556 variants, with 416 potentially actionable variants in 54.88% (309/563) patients. These single nucleotide variants, insertions and deletions were most commonly found in EGFR (55%), followed by ERBB2 (12%), KRAS (11%), PIK3CA (9%), MET (8%), BRAF (7%), DDR2 (2%), NRAS (0.3%). By using ten protein function prediction algorithms, we also identified 30 novel potentially pathogenic variants. Ninety-eight patients harbored EFGR exon 21 p.L858R mutation and the catalytic domain of the protein tyrosine kinase (PTKc) in EGFR is largely mutated. In addition, there were nine frequent pathogenic variants found in five or more patients. This data provides the potential molecular basis for directing the treatment of lung cancer.