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High-grade serous cancer (HGSC) is the most common subtype of ovarian cancer. HGSC is highly aggressive with poor patient outcomes, and a deeper understanding of HGSC tumorigenesis could help guide future treatment development. To systematically characterize the underlying pathologic mechanisms and intratumoral heterogeneity in human HGSC, we used an optimized single-cell multiomics sequencing technology to simultaneously analyze somatic copy-number alterations (SCNA), DNA methylation, chromatin accessibility, and transcriptome in individual cancer cells. Genes associated with interferon signaling, metallothioneins, and metabolism were commonly upregulated in ovarian cancer cells. Integrated multiomics analyses revealed that upregulation of interferon signaling and metallothioneins was influenced by both demethylation of their promoters and hypomethylation of satellites and LINE1, and potential key transcription factors regulating glycolysis using chromatin accessibility data were uncovered. In addition, gene expression and DNA methylation displayed similar patterns in matched primary and abdominal metastatic tumor cells of the same genetic lineage, suggesting that metastatic cells potentially preexist in the subclones of primary tumors. Finally, the lineages of cancer cells with higher residual DNA methylation levels and upregulated expression of CCN1 and HSP90AA1 presented greater metastatic potential. This study characterizes the critical genetic, epigenetic, and transcriptomic features and their mutual regulatory relationships in ovarian cancer, providing valuable resources for identifying new molecular mechanisms and potential therapeutic targets for HGSC.Significance:Integrated analysis of multiomic changes and epigenetic regulation in high-grade serous ovarian cancer provides insights into the molecular characteristics of this disease, which could help improve diagnosis and treatment.

Supplementary Figure from Single-Cell Dissection of the Multiomic Landscape of High-Grade Serous Ovarian Cancer

Supplementary Table from Single-Cell Dissection of the Multiomic Landscape of High-Grade Serous Ovarian Cancer

Supplementary Data from Single-Cell Dissection of the Multiomic Landscape of High-Grade Serous Ovarian Cancer

High-grade serous cancer (HGSC) is the most common subtype of ovarian cancer. HGSC is highly aggressive with poor patient outcomes, and a deeper understanding of HGSC tumorigenesis could help guide future treatment development. To systematically characterize the underlying pathologic mechanisms and intratumoral heterogeneity in human HGSC, we used an optimized single-cell multiomics sequencing technology to simultaneously analyze somatic copy-number alterations (SCNA), DNA methylation, chromatin accessibility, and transcriptome in individual cancer cells. Genes associated with interferon signaling, metallothioneins, and metabolism were commonly upregulated in ovarian cancer cells. Integrated multiomics analyses revealed that upregulation of interferon signaling and metallothioneins was influenced by both demethylation of their promoters and hypomethylation of satellites and LINE1, and potential key transcription factors regulating glycolysis using chromatin accessibility data were uncovered. In addition, gene expression and DNA methylation displayed similar patterns in matched primary and abdominal metastatic tumor cells of the same genetic lineage, suggesting that metastatic cells potentially preexist in the subclones of primary tumors. Finally, the lineages of cancer cells with higher residual DNA methylation levels and upregulated expression of CCN1 and HSP90AA1 presented greater metastatic potential. This study characterizes the critical genetic, epigenetic, and transcriptomic features and their mutual regulatory relationships in ovarian cancer, providing valuable resources for identifying new molecular mechanisms and potential therapeutic targets for HGSC. Significance: Integrated analysis of multiomic changes and epigenetic regulation in high-grade serous ovarian cancer provides insights into the molecular characteristics of this disease, which could help improve diagnosis and treatment.

Objective Hematogenous metastasis is essential for the progression of ovarian cancer (OC), and circulating tumor cells (CTCs) are part of the metastatic cascade. However, the detection rate of CTC is low due to the use of less sensitive detection methods. Therefore, this study aimed to detect CTCs and circulating tumorigenic endothelial cells (CTECs) in patients with OC using subtraction enrichment and immunostaining and fluorescence in situ hybridization (SE-iFISH). Methods We enrolled a total of 56 subjects, including 20 OC patients and 36 ovarian benign tumor patients. CTCs and CTECs were captured by subtraction enrichment (SE) and counted and classified according to immunofluorescence staining of tumor markers (TMs) carbohydrate antigen 125 (CA125) and human epididymis protein 4 (HE4) combined with fluorescence in situ hybridization (iFISH) of chromosome 8 (Chr8) aneuploidy. The diagnostic value and subtype characteristics of CTCs and CTECs were investigated. Results The detection rate of CTCs by SE-iFISH was high. Compared with CA125 and HE4, Chr8 aneuploidy was the major identification feature of CTC. CTC counts in OC were statistically higher than those in benign groups. CTC and CTEC with ≥pentaploidy were detected in both groups, illustrating the poor diagnostic value of CTC or CTEC. Distributions of triploid and tetraploid CTC subtypes were significantly different, and combined detection of triploid and tetraploid CTCs showed the best diagnostic value. In contrast, the distribution of CTECs in the OC and benign groups had no statistically significant difference. Small CTCs accounted for over 1/3 of the total CTC count. We also found that small CTCs and CTECs primarily comprised triploid cells, while large CTCs and CTECs mainly comprised pentaploidy and beyond. Conclusions The application of SE-iFISH offered a more comprehensive understanding of heterogeneous CTCs and CTECs in OC. Analysis of subclass characteristics of the CTCs and CTECs according to Chr8 aneuploidy and cell size may broaden their potential clinical utility and deepen mechanistic studies in OC.

Mechanical optimization design is a new design method in the development foundation of the modern mechanical design theory, the application of optimization design in mechanical design can make the scheme achieve some optimization results in the design requirements specified, without consuming too much computational effort. The corresponding mathematical models of ant algorithm and Cellular ant algorithm are established, according to the actual mechanical design problems, and used to solve the established mathematical model by computer, so as to obtains the optimal design scheme.

In this paper, we construct the travelling wave solutions to the perturbed nonlinear Schrodinger’s equation (NLSE) with Kerr law non-linearity by the extended (G′/G)-expansion method. Based on this method, we obtain abundant exact travelling wave solutions of NLSE with Kerr law nonlinearity with arbitrary parameters. The travelling wave solutions are expressed by the hyperbolic functions, trigonometric functions and rational functions.

The purposed research joins back-propagation neural network (BPNN) algorithm, using NX/KF second development module to create feasible assembly sequences KBE system access the volume, weight, feature, relationship number and total penalty value, and predict the feasible assembly sequence via a robust BPNN engine.

Based on FLOW3D software to study on the air entrapment of melt flow inside the Show Sleeve in Die-Casting processes, the effect of Die-Casting parameters which are diameter of sleeve, filling rate, low velocity of the plunge, find out the corresponding regression Equation, best parameters and simplified formula of the plunge velocity.

Problem Evaluate the response rate of glucocorticoid (GC) and/or immunoglobulin (IVIg) therapy in severe thrombocytopenia of immune thrombocytopenia (ITP) pregnant patients and the influence on maternal and neonatal outcomes. Method of study This is a prospective observational cohort study. Pregnant ITP patients with platelet count less than 30 × 109 /L and their newborn infants participated in this research. Over a 3-year period, 87 patients were allocated to 4 groups: group 1 (n = 18) were treated by oral prednisone, group 2 (n = 20) with IVIg, group 3 (n = 22) with prednisone/methlyprednisone plus IVIg, and group 4 were non-treatment controls (n = 27). Diagnosis and therapy were based on guideline from the 2011 American Society of Hematology criteria, and the initial dose of prednisone was 1 mg/kg day. Their newborns were followed up to 1 year old. Results The response rate among patients who ever received prednisone therapy was 35.5% (11/31) overall, while the IVIg response rate was 55.9% (19/34). The incidence of pregnancy induced hypertension in GC therapy group was significantly higher than controls (22.2% and 13.6% vs 0%). There was no significant difference in neonatal outcomes in treatment groups in comparison with controls. The rate of Neonatal follow-up within 1 year old was 63%, and there is no evidence indicated intrauterine GC exposure influence the growth and development. Conclusion GC therapy of 1 mg/kg for ITP patients during pregnancy is less efficiency than non-pregnant population and increases the incidence of hypertensive disorders. The use of lower starting doses of prednisone may be suggested for use in pregnancy.