Explore the vast range of titles available.

Purpose Cisplatin is a widely used and effective chemotherapeutic agent for most solid malignant tumors. However, cisplatin-induced ototoxicity is a common adverse effect that limits the therapeutic efficacy of tumors in the clinic. To date, the specific mechanism of ototoxicity has not been fully elucidated, and the management of cisplatin-induced ototoxicity is also an urgent challenge. Recently, some authors believed that miR34a and mitophagy played a role in age-related and drug-induced hearing loss. Our study aimed to explore the involvement of miR-34a/DRP-1-mediated mitophagy in cisplatin-induced ototoxicity. Methods In this study, C57BL/6 mice and HEI-OC1 cells were treated with cisplatin. MiR-34a and DRP-1 levels were analyzed by qRT‒PCR and western blotting, and mitochondrial function was assessed via oxidative stress, JC-1 and ATP content. Subsequently, we detected DRP-1 levels and observed mitochondrial function by modulating miR-34a expression in HEI-OC1 cells to determine the effect of miR-34a on DRP-1-mediated mitophagy. Results MiR-34a expression increased and DRP-1 levels decreased in C57BL/6 mice and HEI-OC1 cells treated with cisplatin, and mitochondrial dysfunction was involved in this process. Furthermore, the miR-34a mimic decreased DRP-1 expression, enhanced cisplatin-induced ototoxicity and aggravated mitochondrial dysfunction. We further verified that the miR-34a inhibitor increased DRP-1 expression, partially protected against cisplatin-induced ototoxicity and improved mitochondrial function. Conclusion MiR-34a/DRP-1-mediated mitophagy was related to cisplatin-induced ototoxicity and might be a novel target for investigating the treatment and protection of cisplatin-induced ototoxicity.

Background. Immunotherapy is an important treatment modality for gastric cancer, therefore, it is crucial to understand the regulators of the tumor microenvironment in gastric cancer. Numerous studies have shown that noncoding RNAs have a critical status in the tumor progression, and the influence of competing endogenous RNA (ceRNA) networks on gastric adenocarcinoma has been widely discussed over the years, but the connection between ceRNA networks and the immune microenvironment of cancer is unclear. This study was aimed at exploring how ceRNA networks influence the prognosis of patients with gastric cancer by modulating the tumor microenvironment. Methods. The Gene Expression Omnibus was analyzed to obtain differential expression matrixes of the noncoding RNAs (circular RNAs (circRNAs), microRNAs (miRNAs)), and mRNAs. The Circular RNA Interactome web tool and TargetScan were applied to determine the miRNA binding sites of the circRNAs and miRNA target genes. The Cancer Genome Atlas provided prognostic genes for gastric cancer, and Cytoscape created the ceRNA networks. Real-time quantitative reverse transcription polymerase chain reaction and western blot assay were adopted to find out how the ceRNA network regulates the expression of the hub gene. Additionally, the TISIDB and TIMER databases were used to assess the link between the hub gene and immunotherapy, with TISIDB providing the immune genes that are coexpressed with the hub gene. Furthermore, the immune-gene signature was constructed by using Cox regression analysis. Moreover, the nomogram, which could predict the prognostic role of gastric cancer patients was created on the basis of the immune-gene signature. Results. In gastric cancer, the circ-0007707/miR-429/PDGFD pathway had a differential expression. The results demonstrated that the pathway could regulate the progression and immune microenvironment of gastric cancer by modulating the immune-gene signature, which included two immune genes (TAB1 and CXCR4). Moreover, the low-risk group patients had better survival. Conclusion. The circ-0007707/miR-429/PDGFD pathway may play a regulatory role in the progression and prognosis of gastric cancer by interfering with the tumor microenvironment, and the PDGFD-related immune-gene signature could be considered a moderator of prognostic factor for gastric cancer and to guide immunotherapy programs.

Hepatocellular carcinoma (HCC) is a common malignancy with a poor prognosis worldwide. However, the pathogenesis of HCC remains poorly understood. In this study, we found that NOL12 was significantly overexpressed in independent HCC datasets from TCGA database. We confirmed that the expression level of NOL12 was upregulated in human HCC tissues and cell lines by RT-qPCR. High expression of NOL12 is associated with worse reduced overall survival (OS), high pathological grade, node metastasis, and advanced clinical stage in patients with HCC. Moreover, knockdown of NOL12 dramatically inhibits the proliferation and metastasis of HCC cells in vitro and in vivo. CIBERSORTx analysis revealed that twelve types of tumor-infiltrating immune cells (TICs) are correlated with NOL12 expression. The risk signature based on 8 NOL12-related genes is an independent prognostic factor for patients with HCC. The OS rate of patients in the low-risk score group was better than that in the high-risk score group. In addition, the total tumor mutation burden (TMB) in the high-risk score group increased significantly, and the risk scores could be used as an alternative indicator of immune checkpoint inhibitor (ICI) response. In conclusion, our findings indicated that NOL12 might be involved in the progression of HCC and can be used as a potential therapeutic target. Moreover, the NOL12-related risk signature may have predictive relevance with regard to ICI therapy.

The Chang’E 5 (CE-5) samples represent the youngest mare basalt ever known and provide an access into the late lunar evolution. Recent studies have revealed that CE-5 basalts are the most evolved lunar basalts, yet controversy remains over the nature of their mantle sources. Here we combine Fe and Mg isotope analyses with a comprehensive study of petrology and mineralogy on two CE-5 basalt clasts. These two clasts have a very low Mg# (∼29) and show similar Mg isotope compositions to Apollo low-Ti mare basalts as well as intermediate TiO2 and Fe isotope compositions between low-Ti and high-Ti mare basalts. Fractional crystallization or evaporation during impact cannot produce such geochemical signatures that otherwise indicate a hybrid mantle source that incorporates both early- and late-stage lunar magma ocean (LMO) cumulates. Such a hybrid mantle source would be also compatible with the KREEP-like Rare Earth Elements pattern of CE-5 basalts. Overall, our new Fe–Mg isotope data highlight the role of late LMO cumulate for the generation of young lunar volcanism.

The swimming crab, Portunus trituberculatus , is one of the main aquaculture species in Chinese coastal regions due to its palatability and high economic value. To obtain a better understanding of the genetic diversity of P. trituberculatus in the Bohai Sea, the present study used 40 SSR loci to investigate the genetic diversity and population structure of 420 P. trituberculatus individuals collected from seven populations in the Bohai Sea. Genetic parameters revealed a low level of genetic diversity in the cultured population ( SI  = 1.374, He  = 0.687, and PIC  = 0.643) in comparison with wild populations ( SI  ≥ 1.399, He  ≥ 0.692, and PIC  ≥ 0.651). The genetic differentiation index ( Fst ) and gene flow ( Nm ) ranged from 0.001 to 0.060 (mean: 0.022) and 3.917 to 249.750 (mean: 31.289) respectively, showing a low differentiation among the seven populations of P. trituberculatus . Population structure analysis, phylogenetic tree, and principal component analysis (PCA) demonstrated that the seven groups of P. trituberculatus were divided into four subpopulations (K = 4), but the correlation between genetic structure and geographical distribution was not obvious. These results are expected to provide useful information for the fishery management of wild swimming crabs.

The research into the prevention of sports injuries among the population, particularly juveniles, has become crucial due to the increasing participation in physical exercises like fitness. To assess the difference in T2 values of ankle talar cartilage between weightlifters and healthy volunteers using quantitative magnetic resonance imaging (MRI) technique T2 mapping. Study design: Prospective. Prospective evaluation of T2 values of ankle cartilage of 50 weightlifters (30 adults and 20 juveniles) and 100 healthy volunteers (80 adults and 20 juveniles) using Siemens 3.0 T MRI with PDWI, T1WI, and T2 mapping sequences. Three physicians manually divided the talar cartilage of the ankle joint into six regions of interest. Three physicians utilized the anterior and posterior cut edges of the tibial cartilage as markers to identify the corresponding anterior and posterior cut edges of the talar cartilage on the sagittal MRI images. The medial and lateral sides were defined as half of the talar articular surface on the coronal plane. Differences in T2 values in each cartilage region were compared using independent sample T test or Mann–Whitney U test. The T2 values of talar cartilage were significantly increased in the athlete group relative to the volunteer group (35.11 and 31.99, P < 0.001), with the most significant difference observed in the juvenile athlete group compared to the volunteer group (34.42 and 28.73, P < 0.001). There was a significant difference in the T2 value of ankle talar cartilage between weightlifters and healthy volunteers, and juveniles may be more vulnerable to overuse sports injuries. This study contributes to understanding the cartilage health of juvenile athletes and the prevention of sports injuries.

Background Myogenic factor 6 ( Myf6 ) plays an important role in muscle growth and differentiation. In aquatic animals and livestock, Myf6 contributes to improving meat quality and strengthening the accumulation of muscle flavor substances. However, studies on Myf6 gene polymorphisms in crustaceans have not been reported. Results In the current study, we characterized the Myf6 gene for Portunus trituberculatus to better understand its biological function. The full-length cDNA of Myf6 was 4,101 bp, with a 915 bp open reading frame encoding 304 amino acids. In addition, Myf6 included a conservative bHLH domain. Homology analysis showed that Myf6 shared the highest identity with Penaeus vannamei . Expression pattern analysis of Myf6 in fast- and slow-growing groups revealed that the expression level of the latter was significantly higher than that of the former ( P  < 0.05). qPCR studies revealed that Myf6 was expressed in various tissues with the highest level in muscle. Nineteen single nucleotide polymorphisms (SNPs) of Myf6 were identified and five of them were significantly associated with growth-related traits of P. trituberculatus ( P  < 0.05), including full carapace width, carapace length, body height, and body weight. The AG and GG genotypes of g.1,187,834 A > G exhibited superior growth-related traits than the AA genotype. In the combined genotypes of g.1,187,324 C > T and g.1,187,834 A > G, the average body weight of diplotype D5 (CT-GG) was higher than that of diplotype D1 (CC-AA), D2 (CC-AG), and D3 (CC-GG) in a cultivated population. A haploblock was generated by three significant SNPs (g.1187834 A > G, g.1188616 A > G, and g.1189024 C > A), containing four haplotypes (AAA, AAC, AGC, and GGC), among which GGC haplotype exhibited superior growth traits (full carapace width and body weight) than the AAA haplotype. Conclusions To our knowledge, this is the first report on Myf6 in crustaceans. The results of this study would contribute to elucidating multiple functions of the Myf6 gene in crustaceans and exploring the potential as a candidate gene in selective breeding programs of P. trituberculatus .

Tripartite motif containing 25 (TRIM25), an E3 ubiquitin ligase that plays an important role in bioprocesses, is frequently elevated in malignant tumors. However, it remains unclear how TRIM25 protein expression is regulated in non-small cell lung cancer (NSCLC). Here, we find that TRIM25 is hyper-expressed in NSCLC tissues and associated with poor prognosis of NSCLC patients. Both in vitro and in vivo experiments indicate that TRIM25 facilitates tumor proliferation and metastasis. Mechanistically, acetylation is identified as a critical post-translational modification (PTM) regulating TRIM25 protein stability in NSCLC. The lysine acetyltransferase cAMP-responsive element-binding (CREB)-binding protein (CBP) mediates acetylation of TRIM25 at lysine 392, which is counteracted by the deacetylase Sirtuin 7 (SIRT7). Notably, the acetylation of TRIM25 enhances its interaction with ubiquitin specific peptidase 7 (USP7), resulting in reduced ubiquitination of TRIM25. In summary, our study reveals a novel acetylation modification site, thus providing new insights into an epigenetic regulation of TRIM25 in human cancer, and suggesting that pharmacological inhibition of TRIM25 acetylation is a potential anti-tumor strategy.

Lunar breccias provide crucial insights into the lithological diversity, shock processing and evolution of the lunar crust. Here, we report a unique regolith breccia (CE5C0000YJYX070GP, hereafter CE5C) returned from the Chang’E-5 (CE-5) mission. CE5C is one of the largest CE-5 breccias with a wide variety of lithologies, dominated by basaltic and mineral fragments as well as impact-melted clasts (including mid-Ti glasses, high-Al glasses, and crystal-bearing impact melt clasts). A comprehensive study of petrology and mineralogy on several representative clasts was conducted by integrating Scanning Electron Microscopy (SEM), Tescan Integrated Mineral Analysis (TIMA), Electron Probe Microanalysis (EPMA) and Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) techniques. Evidence is sufficient that CE5C is a mixed mare-highland regolith breccia, with a high percentage of KREEPy material (>20 vol.%), which has not been previously reported in other CE-5 samples. The mid-Ti impact glasses are characterized by high FeO (24.0 wt.%) and intermediate TiO 2 (5.5 wt.%) contents, while the high-Al impact glasses have a chemical composition compatible with KREEP. Integrated with the regional geological context of the CE-5 landing site, we propose that CE5C is likely derived from a mixed region between the P58/Em4 mare unit and its contiguous eastern highlands. Despite the difficulty in assessing the representativeness of CE5C, the substantial presence of KREEPy material may provide valuable clues to the provenance of exotic ejecta, including the identification of unrecognized source craters situated in the eastern periphery of the sampling unit.

Background Previous studies have revealed a reduction in the genetic diversity of P. trituberculatus in Bohai Sea. However, because swimming crabs have been released into this area for some time, it is unclear whether the release of cultured populations from the national breeding farms of swimming crabs in Bohai Bay have affected the population genetics of wild populations of P. trituberculatus . Methods and results In this study, the genetic diversity and population structure of 120 P. trituberculatus specimens in Bohai Bay were investigated using six microsatellite loci, including one wild population and one cultivated population. A total of 132 alleles were identified for all loci. The mean expected ( He ) and observed heterozygosity ( Ho ) were 0.8185 and 0.7759, respectively, thus indicating high levels of genetic diversity for these two populations. Molecular variance analysis (AMOVA) ( F ST  = 0.0180), genetic distance ( D  = 0.1168) and similarity ( S  = 0.8898) indicated that these two populations could not be distinguished genetically. Structural analysis, phylogenetic tree construction, and principal component analysis, showed no significant distinction between the wild and cultivated populations. Finally, we investigated genetic exchange between the two populations by analyzing migration rate ( M ) and gene flow ( Nm ), thus demonstrating significant flow of genetic information. Conclusions These findings contribute information for further breeding schemes for P. trituberculatus , evaluation of its genetic potential and programs for the protection of wild resources.