Reprogramming of metabolism is described in many types of cancer and is associated with the clinical outcomes. However, the prognostic significance of pyrimidine metabolism signaling pathway in lung adenocarcinoma (LUAD) is unclear. Using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets, we found that the pyrimidine metabolism signaling pathway was significantly enriched in LUAD. Compared with normal lung tissues, the pyrimidine metabolic rate–limiting enzymes were highly expressed in lung tumor tissues. The high expression levels of pyrimidine metabolic–rate limiting enzymes were associated with unfavorable prognosis. However, purinergic receptors P2RX1, P2RX7, P2RY12, P2RY13, and P2RY14 were relatively downregulated in lung cancer tissues and were associated with favorable prognosis. Moreover, we found that hypo-DNA methylation, DNA amplification, and TP53 mutation were contributing to the high expression levels of pyrimidine metabolic rate–limiting enzymes in lung cancer cells. Furthermore, combined pyrimidine metabolic rate–limiting enzymes had significant prognostic effects in LUAD. Comprehensively, the pyrimidine metabolic rate–limiting enzymes were highly expressed in bladder cancer, breast cancer, colon cancer, liver cancer, and stomach cancer. And the high expression levels of pyrimidine metabolic rate–limiting enzymes were associated with unfavorable prognosis in liver cancer. Overall, our results suggested the mRNA levels of pyrimidine metabolic rate–limiting enzymes CAD, DTYMK, RRM1, RRM2, TK1, TYMS, UCK2, NR5C2, and TK2 were predictive of lung cancer as well as other cancers.

Purpose: To evaluate the relationships of the triglyceride-glucose (TyG) index with pregnancy-related complications (PRCs) and to clarify the predictability of the TyG index for PRCs. Patients and Methods: Totally of 11,387 women with a singleton pregnancy were prospectively followed until after delivery. Maternal fasting lipids and glucose concentration were measured in the first trimester (11 weeks gestation on average). The TyG index was calculated as ln [triglyceride (mg/dL) × fasting plasma glucose (mg/dL)/2]. We used generalized linear models to calculate the relative risks and 95% confidence intervals. Receiver-operating characteristic curve analysis was employed to assess the ability of the TyG index to predict the risks of PRCs. Results: Smooth spline reveals that the probability of gestational diabetes mellitus (GDM) is intensified with the increasing TyG index. Multivariate logistic regression adjusted for risk factors demonstrates a 1-unit and a 1-SD increment in the TyG index raises the risk of GDM by 3.63 and 1.57 times, respectively. Identically, the risk of GDM maximizes in the TyG quintile 5 (OR: 3.14; 95% CI: 2.55~3.85) relative to the lowest TyG index group. However, no association between TyG index and the risk of other PRCs was observed after full adjustment. The area under receiver operating characteristic curves is 0.647 (95% CI: 0.632– 0.66) for GDM, and the optimal predictive cut-off is 8.55, with a specificity of 0.679 and sensitivity of 0.535. Conclusion: The first-trimester TyG index is significantly associated with the risk of incident GDM, while the relationships between the TyG index and other PRCs need further exploration.

E2F transcription factors are associated with the development of cancer. However, the E2F family genes have not yet been studied in a comprehensive manner. Using The Cancer Genome Atlas, the present study analyzed the functions of the E2F family genes across different types of tumor. It was revealed that compared with normal tissues, the E2F family genes are highly expressed in several types of tumor tissue. Furthermore, E2F transcription factors were significantly enriched in tumor samples across different types of tumor. The high expression levels of E2F family genes were associated with an unfavorable prognosis in liver hepatocellular carcinoma (LIHC) and lung adenocarcinoma (LUAD). Furthermore, patients with pathological T1 stage and iCluster2 molecular subtype of LIHC expressed particularly low levels of E2F family genes. The present study demonstrated that hypo‑DNA methylation, DNA amplification and TP53 mutation contributed to the high expression levels of E2F family genes in cancer cells. Finally, the present study revealed that, compared with other types of tumor, the E2F family genes were specifically downregulated in patients with LIHC. The expression levels and prognostic effects of the E2F family genes were validated using the Gene Expression Omnibus database. The results of the present study revealed the biological functions of E2F family genes in the development of cancer and provided potential biomarkers for further therapeutic studies, particularly for patients with LIHC and LUAD.

Early organogenesis is a crucial stage in embryonic development, characterized by extensive cell fate specification to initiate organ formation but also by a high susceptibility to developmental defects. Here, we profiled 285 serial sections from six E7.5-E8.0 embryos to generate full spatiotemporal transcriptome and signal maps during early organogenesis at single-cell resolution. By developing SEU-3D, we reconstructed digital embryos, enabling investigation of regionalized gene expression in the native spatial context. We established a space-informed gene-cell co-embedding approach, systematically characterized the spatial atlas of endoderm and mesoderm derivatives, and elucidated signaling networks across germ layers and cell types. Furthermore, we characterized a primordium determination zone (PDZ) formed along the anterior embryonic-extraembryonic interface at E7.75, and it revealed that the coordinated signaling communications contribute to the formation of cardiac primordium. Collectively, the high-resolution "digital embryo" provides significant insights into early organogenesis and a unique spatial platform for studying development and diseases.