A central goal of evolutionary developmental biology is to decipher the evolutionary pattern of gene regulatory networks (GRNs) that control embryonic development, and the mechanism underlying GRNs evolution. The Nodal signaling that governs the body axes of deuterostomes exhibits a conserved GRN orchestrated principally by Nodal, Gdf1/3, and Lefty. Here we show that this GRN has been rewired in cephalochordate amphioxus. We found that while the amphioxus Gdf1/3 ortholog exhibited nearly no embryonic expression, its duplicate Gdf1/3-like, linked to Lefty, was zygotically expressed in a similar pattern as Lefty. Consistent with this, while Gdf1/3-like mutants showed defects in axial development, Gdf1/3 mutants did not. Further transgenic analyses showed that the intergenic region between Gdf1/3-like and Lefty could drive reporter gene expression as that of the two genes. These results indicated that Gdf1/3-like has taken over the axial development role of Gdf1/3 in amphioxus, possibly through hijacking Lefty enhancers. We finally demonstrated that, to compensate for the loss of maternal Gdf1/3 expression, Nodal has become an indispensable maternal factor in amphioxus and its maternal mutants caused axial defects as Gdf1/3-like mutants. We therefore demonstrated a case that the evolution of GRNs could be triggered by enhancer hijacking events. This pivotal event has allowed the emergence of a new GRN in extant amphioxus, presumably through a stepwise process. In addition, the co-expression of Gdf1/3-like and Lefty achieved by a shared regulatory region may have provided robustness during body axis formation, which provides a selection-based hypothesis for the phenomena called developmental system drift.

Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder with elusive molecular mechanisms. This study explores the competitive endogenous RNA (ceRNA) regulatory network in the cumulus cells of PCOS patients. ceRNAs are transcripts like mRNAs, miRNAs, and lncRNAs that competitively bind shared miRNAs, regulating gene expression post-transcriptionally. We analyzed mRNA, microRNA (miRNA), and long non-coding RNA (lncRNA) from two cohorts: 12 PCOS patients and 11 healthy controls (dataset GSE10946), and 5 PCOS patients and 5 healthy controls (dataset GSE72274). These microarray datasets, obtained from the Gene Expression Omnibus (GEO), helped us identify differentially expressed mRNAs, miRNAs, and lncRNAs. Our analysis revealed a significant ceRNA network, which may play a crucial role in the pathophysiology of PCOS. In this network, 5 lncRNAs, 3 miRNAs, and 36 mRNAs were identified as differentially expressed. These elements form a complex regulatory schema influencing key cellular processes related to the disease, such as cell cycle regulation and response to estrogen. The HOXA11-AS-hsa-miR-454-3p-CCND2 network emerged as a potentially valuable biomarker for PCOS diagnosis, supported by Receiver Operating Characteristic (ROC) curve analysis indicating strong predictive power. Our findings suggest that the ceRNA interactions in PCOS cumulus cells provide a deeper understanding of the disease's molecular basis and offer new avenues for therapeutic intervention. This in silico study lays the groundwork for further experimental validation of these ceRNA networks as targets for PCOS treatment.

Objective:To investigate the microRNA (miRNA) expression features in ectopic endometrial tissues of endometriosis (EMS) patients.Methods:From April 2018 to October 2019, ectopic endometrial tissues from EMS patients and eutopic endometrial tissues from control women who received treatment in the Department of Obstetrics and Gynecology of The First Affiliated Hospital of Xiamen University were used in subsequent experiments. Differentially expressed miRNAs were screened out in ectopic endometrial tissues by detecting miRNA sequence from Illumina. The potential roles of these differentially expressed miRNAs and their potential targeted genes in pathogenesis of EMS were analyzed by bioinformatics, and the differential expression levels of 6 miRNAs (miR-98-5p, miR-495-3p, let-7c-5p, miR-200b-3p, miR-200c-3p, miR-148b-3p) were validated by quantitative real-time polymerase chain reaction (qRT-PCR) and subsequently used to build the miRNA-gene regulatory network, then we verified its potential target gene.Results:The microarray results showed that 69 miRNAs might be differentially expressed in ectopic endometrial tissues compared with those in eutopic endometrial tissues (fold change>1.5, P<0.05), including 22 up-regulated miRNAs and 47 down-regulated miRNAs. Gene ontology (GO) analysis showed that the target genes of these differentially expressed miRNAs mainly participated in the protein modification, regulation of development, cell metabolism and morphological structure. KEGG pathway analysis showed that these targeted genes were involved in protein function, autophagy, AGE-RAGE and MAPK signaling pathways. The expression levels of miR-98-5p, let-7c-5p, miR-200b-3p and miR-200c-3p were validated to be significantly altered in ectopic endometrial tissues. The miRNA-gene co-expression network revealed the correlation between the 4 miRNAs and their predicted target genes. qRT-PCR validated results showed that the expression of miR-200b-3p and miR-200c-3p were significantly negatively correlated with ZEB2, while miR-98-5p was negatively correlated with PGRMC1, miR-98-5p and let-7c-5p were positively correlated with ADIPOR2. Conclusion:MiR-98-5p, let-7c-5p, miR-200b-3p and miR-200c-3p were significantly differentially expressed in the ectopic endometrial tissues of EMS patients, which may be involved in the development of EMS.

Skeletal muscle development is a complex biological process involving multiple key genes, signaling pathways and noncoding RNAs, including microRNAs and circular RNAs (circRNAs). However, the regulatory relationship among them is so complicated that it has not yet been fully elucidated. In this study, we found that miR‐7 inhibited C2C12 cell proliferation and differentiation by targeting transcription factor 12 ( TCF12 ). circHIPK3 acted as a competing endogenous RNA, and its overexpression effectively reversed the regulation of miR‐7 on C2C12 cell proliferation and differentiation by increasing TCF12 expression. Taken together, our findings provide evidence that circHIPK3 regulates skeletal muscle development through the miR‐7/ TCF12 pathway. This study provides a scientific basis for further research on skeletal muscle development at the circRNA level.

Purpose: This study aimed to reveal the molecular differences in granulosa cells (GCs) from patients with endometriosis (EM). Methods: RNA sequencing was performed on GCs from patients with EM-related infertility (n = 3) and controls (n = 3). Differentially expressed long noncoding RNAs [differentially expressed lncRNAs (DELs), |log2 FC|>4, false discovery rate (FDR) <0.05] and genes [differentially expressed genes (DEGs), |log2 FC|>1.4, FDR <0.05] in patients with EM-related infertility and controls were screened. Protein-protein interaction (PPI) networks of the DEGs were constructed. Then, mRNA-miRNA-lncRNA pairs based on DEGs and DELs were constructed by comprehensive bioinformatics analyses. In addition, overlapping genes identified from both the PPI and mRNA-miRNA-lncRNA pairs were selected. Finally, a competing endogenous RNA (ceRNA) network incorporating transcription factors (TFs) was constructed. Results: A total of 25,806 lncRNAs and 19,684 mRNAs were detected, and 7 DELs and 46 DEGs were identified. Five hub genes from the PPI network were also identified. A single overlapping gene, NR4A2, from both the PPI network and mRNA-miRNA-lncRNA pairs was identified. Finally, a ceRNA network incorporating TFs, including one mRNA (NR4A2), one miRNA (hsa-miR-217), three lncRNAs (XIST, MCM3AP-AS1, and C17orf51), and five TFs (SRF, POLR2A, NRF1, MNT, and TCF7L2), was successfully constructed. Conclusions: The proposed ceRNA network and the prediction of TFs in GCs from EM-related infertility revealed differences in GCs from patients with EM. Importantly, the novel TFs, lncRNAs, miRNAs, and mRNAs involved in the ceRNA network might provide new insights into the underlying molecular mechanisms of EM-related infertility.

目的:研究分析系统化护理干预对复杂踝关节骨折患者术后恢复、疼痛程度及生活质量的影响.方法:选取2016年7月-2018年6月于本院进行踝关节骨折手术治疗的患者86例为研究对象.按随机数字表法将其分为观察组与对照组,各43例.观察组予以系统化护理干预,对照组予以常规护理.比较不同护理干预对两组患者术后恢复、疼痛程度及生活质量的影响.结果:观察组患者术后下床活动时间、住院时间、完全负重时间、骨折愈合时间均短于对照组,差异均有统计学意义(P<0.05).观察组患者实施系统化护理干预后疼痛缓解总有效率高于对照组,差异有统计学意义(P<0.05).观察组实施系统化护理干预后角色功能、情绪功能、躯体功能、社会功能评分均高于对照组,差异均有统计学意义(P<0.05).结论:复杂踝关节骨折患者在手术治疗后的护理干预中,系统化护理干预可以有效促进患者术后恢复,减轻疼痛程度,改善生活质量.

Aim: To explore the circular RNA (circRNA) profile in cumulus cells from endometriosis-associated infertility patients. Methods: The expression of circRNAs was profiled by high-throughput sequencing. Sanger sequencing was performed to identify the backsplicing site. Six candidate circRNAs and their parental genes were measured in 30 samples by quantitative reverse transcription-polymerase chainreaction (qRT-PCR). Bioinformatics analysis was performed to predict the functions. Results: A total of 55 upregulated and 41 downregulated differentially expressed circRNAs were detected. Kyoto Encyclopedia of Genes and Genomes data indicated that these target genes were mainly involved in cumulus cell growth- and differentiation-related pathways. Hsa_circ_0072391, hsa_circ_0007299 and hsa_circ_0057799 were significantly increased, and hsa_circ_001533 was significantly decreased in endometriosis-associated infertility patients. Conclusion: The differentially expressed circRNAs might be potentially involved in pathophysiology of endometriosis-associated infertility.