The Pacific oyster Crassostrea gigas is a commercially important bivalve in aquaculture worldwide. C. gigas has a fascinating sexual reproduction system consisting of dioecism, sex change, and occasional hermaphroditism, while knowledge of the molecular mechanisms of sex determination and differentiation is still limited. In this study, the transcriptomes of male and female gonads at different gametogenesis stages were characterized by RNA-seq. Hierarchical clustering based on genes differentially expressed revealed that 1269 genes were expressed specifically in female gonads and 817 genes were expressed increasingly over the course of spermatogenesis. Besides, we identified two and one gene modules related to female and male gonad development, respectively, using weighted gene correlation network analysis (WGCNA). Interestingly, GO and KEGG enrichment analysis showed that neurotransmitter-related terms were significantly enriched in genes related to ovary development, suggesting that the neurotransmitters were likely to regulate female sex differentiation. In addition, two hub genes related to testis development, lncRNA LOC105321313 and Cg-Sh3kbp1, and one hub gene related to ovary development, Cg-Malrd1-like, were firstly investigated. This study points out the role of neurotransmitter and non-coding RNA regulation during gonad development and produces lists of novel relevant candidate genes for further studies. All of these provided valuable information to understand the molecular mechanisms of C. gigas sex determination and differentiation.

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Epithelial ovarian cancer (EOC) is the deadliest gynecological cancer, and the major cause of death is mainly attributed to metastasis. MicroRNAs (miRNAs) are a group of small non-coding RNAs that exert important regulatory functions in many biological processes through their effects on regulating gene expression. In most cases, miRNAs interact with the 3′ UTRs of target mRNAs to induce their degradation and suppress their translation. Aberrant expression of miRNAs has been detected in EOC tumors and/or the biological fluids of EOC patients. Such dysregulation occurs as the result of alterations in DNA copy numbers, epigenetic regulation, and miRNA biogenesis. Many studies have demonstrated that miRNAs can promote or suppress events related to EOC metastasis, such as cell migration, invasion, epithelial-to-mesenchymal transition, and interaction with the tumor microenvironment. In this review, we provide a brief overview of miRNA biogenesis and highlight some key events and regulations related to EOC metastasis. We summarize current knowledge on how miRNAs are dysregulated, focusing on those that have been reported to regulate metastasis. Furthermore, we discuss the role of miRNAs in promoting and inhibiting EOC metastasis. Finally, we point out some limitations of current findings and suggest future research directions in the field.

The mechanistic (formally “mammalian”) target of rapamycin (mTOR) pathway serves as a crucial regulator of various biological processes such as cell growth and cancer progression. In bladder cancer, recent discoveries showing the cancer-promoting role of mTOR complex 1 have attracted wide attention. However, the regulation of mTOR signaling in bladder cancer is complicated and the underlying mechanism remains elusive. Here, we report that the deubiquitinating enzyme, ovarian tumor domain-containing protein 5 (OTUD5), can activate the mTOR signaling pathway, promote cancer progression, and show its oncogenic potential in bladder cancer. In our study, we found that OTUD5 deubiquitinated a RING-type E3 ligase, RNF186, and stabilized its function. In addition, the stabilization of RNF186 further led to the degradation of sestrin2, which is an inhibitor of the mTOR signaling pathway. Together, we provide novel insights into the pathogenesis of bladder cancer and first prove that OTUD5 can promote bladder cancer progression through the OTUD5-RNF186-sestrin2-mTOR axis, which may be exploited in the future for the diagnosis and treatment of this malignancy.

BackgroundMetastatic recurrence remains a major cause of colorectal cancer (CRC) mortality. In this study, we focused on the role and the potential underlying mechanisms of nuclear factor of activated T cells 1 (NFATc1) in CRC metastasis. MethodsWe examined the expression of NFATc1 in 140 cases of CRC tissues and 35 corresponding adjacent tissues, as well as analyzed the correlation between NFATc1 expression levels and clinical stages. The role of NFATc1 in CRC metastasis and the molecular mechanisms were investigated in both in vitro and in vivo models. ResultsThe results showed that NFATc1 expression was increased in metastatic CRC tissues and positively associated with clinical stages (Stage I vs. Stage II, III or IV) of CRC. Overexpression of NFATc1 promoted CRC cell migration, invasion and epithelial-mesenchymal transition (EMT). Moreover, SNAI1 was veri ed as the direct transcriptional target of NFATc1 and interacted with Slug to promote EMT. Remarkably, our lung and liver double metastasis mouse model demonstrated that NFATc1 overexpression accelerated CRC metastasis, and treatment with FK506, a calcineurin-NFAT pathway inhibitor, could suppress CRC metastasis in vivo. ConclusionsTaken together, our ndings suggest that NFATc1 could transcriptionally activate SNAI1, which in turn could interact with Slug to mediate EMT and to promote CRC metastasis, making NFATc1 a promising target in CRC treatment.

BackgroundSerum uric acid (SUA) has been proven to be closely associated with metabolic abnormalities, including obesity. This study aimed to investigate the detailed relationship between total percent fat (TPF) and SUA among adults.MethodsBriefly, 23,715 adults aged 18–59 years in the National Health and Nutrition Examination Survey (NHANES) 1999–2018 were included in this study. Multivariable linear regression models were used to examine the association between TPF and SUA. Subgroup analyses stratified by sex and obesity status were also performed by multivariable linear regression. Then, fitted smoothing curves and generalized additive models were also applied to address the non-linear relationship between TPF and SUA. Finally, a recursive algorithm was used to calculate the inflection point in the non-linear relationship and a two-segment piecewise linear regression model was used to analyze the relationship between TPF and SUA on both sides of the inflection point.ResultsThere were 15,808 (66.7%) obese individuals in all 23,715 participants. In the fully adjusted model, there was a positive association between TPF and SUA (β = 0.99, 95% CI: 0.73–1.26). Besides, this positive association remained statistically significant in subgroup analyses stratified by sex and obesity status. Interestingly, in males, the association of TPF and SUA was an inverted U-shaped curve (inflection point: 34.3%).ConclusionOur study revealed a significant positive relationship between TPF and SUA among adults and this association remained statistically significant when stratified by sex and obesity status, but the shape of the smoothing curve in males differed from that in females.

The early diagnosis of pulmonary cancer can significantly improve the survival rate of patients, where pulmonary nodules detection in computed tomography images plays an important role. In this article, we propose a novel pulmonary nodule detection system based on convolutional neural networks (CNN). Our system consists of two stages, pulmonary nodule candidate detection and false positive reduction. For candidate detection, we introduce Iterative Self-Organizing Data Analysis Techniques Algorithm (ISODATA) to Faster Region-based Convolutional Neural Network (Faster R-CNN) model. For false positive reduction, a three-dimensional convolutional neural network (3D-CNN) is employed to completely utilize the three-dimensional nature of CT images. In this network, Focal Loss is used to solve the class imbalance problem in this task. Experiments were conducted on LUNA16 dataset. The results show the preferable performance of the proposed system and the effectiveness of using ISODATA and Focal loss in pulmonary nodule detection is proved.

Taurine has been reported high amounts in marine animals to maintain osmotic balance between osmoformers and sea water. Approximately 80% of the total amino-acid content is taurine in Pacific oyster Crassostrea gigas, an intertidal and euryhaline species. In this study, we cloned the two copies of cysteine sulfinate decarboxylase (CSAD), the key enzyme in taurine biosynthesis pathway, screened in oyster genome data. Sequentially, we compared the expression patterns of CgCSAD1 and CgCSAD2 under low salinity treatment (8‰ and 15‰) using different families from two populations. There was no correlation between the expression of CSAD and the different population. Notably, CgCSAD1 increased significantly in treated groups for 24 h, but CgCSAD2 had no significant differentiation. Moreover, the results of CgCSAD1 interference provided the evidence of the positive correlation between CgCSAD1 expressions and taurine contents. The zinc finger domain showed in multi-alignment results may be the important character of CgCSAD1 as the key enzyme in taurine biosynthesis to regulate taurine pool in response to low salinity. This study provides a new evidence for the important role of taurine in adaptation to low salinity in oyster. In addition, it is a good model to discuss the function and evolution of the duplication in mollusks.