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Transmembrane protein 52B (TMEM52B), a newly identified tumor‐related gene, has been reported to regulate various tumors, yet its role in nasopharyngeal carcinoma (NPC) remains unclear. Transcriptomic analysis of NPC cell lines reveals frequent overexpression of TMEM52B, and immunohistochemical results show that TMEM52B is associated with advanced tumor stage, recurrence, and decreased survival time. Depleting TMEM52B inhibits the proliferation, migration, invasion, and oncogenesis of NPC cells in vivo. TMEM52B encodes two isoforms, TMEM52B‐P18 and TMEM52B‐P20, differing in their N‐terminals. While both isoforms exhibit similar pro‐oncogenic roles and contribute to drug resistance in NPC, TMEM52B‐P20 differentially promotes metastasis. This functional discrepancy may be attributed to their distinct subcellular localization; TMEM52B‐P18 is confined to the cytoplasm, while TMEM52B‐P20 is found both at the cell membrane and in the cytoplasm. Mechanistically, cytoplasmic TMEM52B enhances AKT phosphorylation by interacting with phosphoglycerate kinase 1 (PGK1), fostering NPC growth and metastasis. Meanwhile, membrane‐localized TMEM52B‐P20 promotes E‐cadherin ubiquitination and degradation by facilitating its interaction with the E3 ubiquitin ligase NEDD4, further driving NPC metastasis. In conclusion, the TMEM52B‐P18 and TMEM52B‐P20 isoforms promote the metastasis of NPC cells through different mechanisms. Drugs targeting these TMEM52B isoforms may offer therapeutic benefits to cancer patients with varying degrees of metastasis. [ABSTRACT FROM AUTHOR]

Introduction: This study investigates the characteristics of sediment disturbance caused by impeller rotation in reservoirs of inland rivers with high sediment content in China. A scaled experimental model, reflecting typical environmental conditions of inland water reservoirs in Northwest China, was established in Lanzhou, Gansu Province, following the principle of similarity. Methods: The study integrates numerical simulations using Ansys Fluent software and corroborates the findings through hydraulic experiments. Computational Fluid Dynamics (CFD) and the κ-ε Realizable model were employed to simulate the solid-liquid mixing process, which was verified against the experimental model. Results: The results indicate that increasing the impeller velocity from 2 rad/s to 8 rad/s, while submerged at a depth of 1000 mm in the flow field, enhances the rate of bottom sediment suspension. Furthermore, the rate of suspended sediment discharge from the model outlet increased with inflow velocity ranging from 0.1 m/s to 0.8 m/s. A decrease in the impeller's submersion depth from 600 mm to 1200 mm was found to reduce the maximum disturbance radius affecting the bottom sediment. Discussion: The reliability of the simulation was confirmed by comparing the software results with experimental data. This study provides insights into the mechanisms of sediment-laden flow disturbance in the reservoir areas of inland rivers in China and lays the groundwork for more comprehensive investigations into sediment discharge in these environments. [ABSTRACT FROM AUTHOR]

Despite being a non-hematophagous leech, Whitmania pigra is widely used in traditional Chinese medicine for the treatment of antithrombotic diseases. In this study, we provide a high quality genome of W. pigra and based on which, we performed a systematic identification of the potential antithrombotic genes and their corresponding proteins. We identified twenty antithrombotic gene families including thirteen coagulation inhibitors, three platelet aggregation inhibitors, three fibrinolysis enhancers, and one tissue penetration enhancer. Unexpectedly, a total of 79 antithrombotic genes were identified, more than a typical blood-feeding Hirudinaria manillensis, which had only 72 antithrombotic genes. In addition, combining with the RNA-seq data of W. pigra and H. manillensis, we calculated the expression levels of antithrombotic genes of the two species. Five and four gene families had significantly higher and lower expression levels in W. pigra than in H. manillensis, respectively. These results showed that the number and expression level of antithrombotic genes of a non-hematophagous leech are not always less than those of a hematophagous leech. Our study provides the most comprehensive collection of antithrombotic biomacromolecules from a non-hematophagous leech to date and will significantly enhance the investigation and utilization of leech derivatives in thrombosis therapy research and pharmaceutical applications. [ABSTRACT FROM AUTHOR]

Background: Congenital ectopia lentis (EL) refers to the congenital dysplasia or weakness of the lens suspensory ligament, resulting in an abnormal position of the crystalline lens, which can appear as isolated EL or as an ocular manifestation of a syndrome, such as the Marfan syndrome. The fibrillin‐1 protein encoded by the FBN1 gene is an essential component of the lens zonules. Mutations in FBN1 are the leading causes of congenital EL and Marfan syndrome. Owing to the complexity and individual heterogeneity of FBN1 gene mutations, the correlation between FBN1 mutation characteristics and various clinical phenotypes remains unclear. Methods: This study describes the clinical characteristics and identifies possible causative genes in eight families with Marfan syndrome or isolated EL using Sanger and whole‐exome sequencing. Results: Eight FBN1 mutations were identified in these families, of which three (c.5065G > C, c.1600 T > A, and c.2210G > C) are reported for the first time. Based on in silico analyses, we hypothesized that these mutations may be pathogenic by affecting the fibrillin‐1 protein structure and function. Conclusion: These findings expand the number of known mutations involved in EL and provide a reference for the research on their genotype and phenotype associations. [ABSTRACT FROM AUTHOR]

Adipose differentiation-related protein (ADRP) is a lipid droplet-associated protein that is expressed early during adipose differentiation. However, the underlying mechanism is still unclear. In this study, the porcine ADRP (pADRP) gene regulatory mechanism and its relationship to intramuscular fat (IMF) content are analysed. We investigated the characteristics of the pADRP gene prompter as well as its transcription level, core promoter and epigenetic modification status using real-time PCR, Dual-luciferase reporter assays and bisulphite sequencing. The results showed that pADRP mRNA expression in Longissimus Dorsi (LD) muscle of the low IMF (LEAN) group was lower than that in the high IMF (FAT) group (p<.01). Maximum promoter activity was found in the −926 bp to −235 bp region. The methylation level of the pADRP of this region (mainly 7th, 10th, 12th CpG sites) in the low IMF group (86.67%) was significantly higher than that in the high IMF group (46.7%) (p<.01). Our result plays an important role in pADRP transcriptional regulation and provides a good prospect for the marbling traits improvement. pADRP expression differs in divergent IMF content pigs. Promoter region located −929 to −235 bp, and its methylation contributes to gene expression. [ABSTRACT FROM AUTHOR]

The c-Jun N-terminal protein kinase (JNK) plays an important role in the regulation of cell apoptosis. Forkhead box O (FoxO) transcription factors are involved in diverse biological processes, including cellular metabolism, cell apoptosis, and cell cycle. However, the JNK/FoxO1 pathway involved in the process of apoptosis induced by oxidative stress remains to be elucidated. Here, we demonstrated that the JNK activity significantly increased in response to oxidative stress in mouse follicular granulosa cells (MGCs). SP600125, a selective JNK inhibitor, attenuated the oxidative stress-induced MGCs apoptosis. Oxidative stress enhanced the FoxO1 nuclear translocation by activating the JNK activity. Moreover, JNK mediated the dissociation of FoxO1 from 14-3-3 proteins in MGCs after the treatment with H2O2. Finally, oxidative stress up-regulated the expression of FoxO1 via JNK mediation of FoxO1 self-regulation in MGCs. Taken together, our findings suggest that JNK/FoxO1 is involved in the regulation of oxidative stress-induced cell apoptosis in MGCs. [ABSTRACT FROM AUTHOR]

Simple Summary: The improvement of porcine meat quality is one of the most challenging tasks in pig breeding. The identification and utilization of major genes and variations affecting meat quality traits has become a research hotspot in molecular breeding of pigs. In this study, we analyzed the characteristics of porcine Prospero-related homeobox 1 (Prox1) gene to lay a solid foundation for further functional study. The expression pattern of Prox1, as well as the correlation and association analysis of Prox1 with meat quality traits, indicates that Prox1 can be targeted to improve porcine meat quality traits. Prox1 is involved in muscle fiber conversion, adult-onset obesity, and type 2 diabetes. However, information regarding porcine Prox1 and its relationship with meat quality traits is still unknown. In this study, we characterized the full-length cDNA and proximal promoter of two transcript variants of porcine Prox1. Moreover, Prox1 was expressed abundantly in the skeletal muscle and its expression was higher in the soleus muscle than that in the biceps femoris muscle. Its expression pattern in the high and low meat color (redness) value a* groups was similar to that of myoglobin and MyHC I, but opposed to that of MyHC IIB. Importantly, there was a significant positive correlation between Prox1 expression and meat color (redness) value a* (r = 0.3845, p = 0.0394), and a significant negative correlation between Prox1 expression and drip loss (r = −0.4204, p = 0.0232), as well as the ratio of MyHC IIB to MyHC I expression (r = −0.3871, p = 0.0380). In addition, we found that the polymorphisms of three closely linked SNPs in Prox1 promoter 1 were significantly associated with pH24h in a pig population. Taken together, our data provide valuable insights into the characteristics of porcine Prox1 and indicate that Prox1 is a promising candidate gene affecting meat quality traits. [ABSTRACT FROM AUTHOR]

The medicinal leeches have been widely utilized in medical procedures for thousands of years. Recently, there were more and more transcriptomes of leech published online including the medicinal leech ( Hirudo medicinalis ) and some other leeches. However, leech's genetic backgrounds are still largely unknown. In this report, transcriptomes of three phylogenetically close leeches ( Poecilobdella javanica , Whitmania pigra , and Haemadipsa cavatuses ) were established by RNA-seq technique for studying their genetic mechanisms of environmental adaption. Over 110 million high-quality reads were generated and assembled into unique transcriptome (reads = 200 bp). 27,138 out of de novo assembled transcripts (41.77%) were assigned to one or more GO terms. Additionally, the transcripts were detected in 217 predicted KEGG pathways. The enriched genes were involved in protein metabolism, GPCRs and pathogen-resistant pathways. The results showed that the great variations existed in gene expression of olfactory transduction pathway among three leech species. The comparisons of leech species hinted at the underlying mechanism of leeches adapting well in various environments. Our study will provide useful rationales for future studies of leeches and other annelid species. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are a class of ~ 22-nt non-coding small RNA that play an important role in various metabolic processes, mainly through suppressing the expression of protein coding genes at post-transcriptional level. Drip loss (DL) is one of the most important meat quality traits affecting the end product yield and quality of pork. To date, the underlying regulatory factors involved in DL trait are still incompletely understood. In the present study, we constructed two small RNA libraries with longissimus dorsi muscles from the higher DL (WJJ-H group) and the lower DL (WJJ-L group) individuals, and applied RNA-Seq technology to identify the differentially expressed miRNAs between the two extreme phenotypes of DL groups. A total of 184 and 176 porcine known miRNAs were detected from WJJ-H and WJJ-L groups, respectively. Moreover, 73 differentially expressed miRNAs were identified between two groups, of which 40 were up-regulated and 33 were down-regulated. In addition, 133 and 140 novel potential miRNAs were predicted from WJJ-H and WJJ-L groups, respectively. Notably, we preliminary confirmed that both miRNA-499 and miRNA-22 were potential candidates influencing DL trait by their expression pattern analysis. Overall, our data enhance the knowledge of porcine skeletal muscle miRNAs, and provide foundation for clarifying the miRNA regulatory mechanisms involved in DL trait. [ABSTRACT FROM AUTHOR]

As an important type of somatic cell, granulosa cells play a major role in deciding the fate of follicles. Therefore, analyses of granulosa cell apoptosis and follicular atresia have become hotspots of animal research. Autophagy is a cellular catabolic mechanism that protects cells from stress conditions, including starvation, hypoxia, and accumulation of misfolded proteins. However, the relationship between autophagy and apoptosis in granulosa cells is not well known. Here, we demonstrate that let-7g regulates the mouse granulosa cell autophagy signaling pathway by inhibiting insulin-like growth factor 1 receptor expression and affecting the phosphorylation of protein kinase B/mammalian target of rapamycin. Small interference-mediated knockdown of insulin-like growth factor 1 receptor significantly promoted autophagy signaling of mouse granulosa cells. In contrast, overexpression of insulin-like growth factor 1 receptor in mouse granulosa cells attenuated autophagy activity in the presence of let-7g. In addition, overexpression of let-7g increased the apoptosis rate, as indicated by an increased number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive cells. Finally, 3-methyladenine as well as the lysosomal enzyme inhibitor chloroquine partially blocked apoptosis. In summary, this study demonstrates that let-7g regulates autophagy in mouse granulosa cells by targeting insulin-like growth factor 1 receptor and downregulating protein kinase B/mammalian target of rapamycin signaling, and that mouse granulosa cell autophagy induced by let-7g participates in apoptosis. [ABSTRACT FROM AUTHOR]

Follicular atresia mainly results from apoptosis of granulosa cells (GCs). Our previous microRNA array data indicated that the miRNA let-7g level increases significantly during porcine ovary follicular atresia. It is uncertain if GCs apoptosis is mediated by microRNA let-7g. In this study, the expression levels of the apoptosis-associated genes CASP3 , BAX and BIM were significantly upregulated when let-7g mimic was transfected into porcine GCs, and the anti-apoptotic genes BCL-2 and MCL-1 were significantly downregulated. The apoptosis rate was measured by flow cytometry, and our results indicated that let-7g significantly enhanced GCs apoptosis. In further studies, we found that overexpression of let-7g induced the expression of FoxO1 in GCs and led to nuclear accumulation of dephosphorylated FoxO1. In addition, the effect of let-7g on FoxO1 expression and dephosphorylation resulted from repression of the expression of the MAP3K1 gene in porcine GCs. The site on MAP3K1 mRNA targeted by let-7g was confirmed by luciferase reporter assay. The anti-apoptotic effect of MAP3K1 was validated by silencing MAP3K1 using small interfering RNA technology. In conclusion, our data indicate that let-7g induces porcine GCs apoptosis by inhibiting the MAP3K1 gene, which promotes FoxO1 expression and dephosphorylation with nuclear accumulation. [ABSTRACT FROM AUTHOR]