Parkprince7864

Purpose Congenital cataract (CC) is a common disease resulting in leukocoria and the leading cause of blindness in children worldwide. Approximately 50% of congenital cataract is inherited. Our aim is to identify mutations in a Chinese family with congenital cataract. Methods A four-generation Chinese family diagnosed with congenital cataract was recruited in West China Hospital of Sichuan University. Y-27632 ROCK inhibitor Genomic DNA was extracted from the peripheral blood of these participants. All coding exons and flanking regions were amplified and sequenced, and the variants were validated using Sanger sequencing. AlphaFold2 was used to predict possible protein structural changes in this variant. Results The proband had congenital nuclear cataract with nystagmus. A heterozygous variant c.233C > T was identified in exon 2 of the CRYGD gene in chromosome 2. This mutation resulted in a substitution of serine with phenylalanine at amino acid residue 78 (p.S78F). The variant might result in a less stable structure with a looser loop and broken hydrogen bond predicted by AlphaFold2, and this mutation was co-segregated with the disease phenotype in this family. Conclusion We described cases of human congenital cataract caused by a novel mutation in the CRYGD gene and provided evidence of further phenotypic heterogeneity associated with this variant. Our study further extends the mutation spectrum of the CRYGD gene in congenital cataract.Recent studies have identified a role for ALKBH7 in the occurrence and progression of cancer, and this protein is related to cellular immunity and immune cell infiltration. However, the prognostic and immunotherapeutic value of ALKBH7 in different cancers have not been explored. In this study, we observed high ALKBH7 expression in 17 cancers and low expression in 5 cancers compared to paired normal tissues. Although ALKBH7 expression did not correlate relatively significantly with the clinical parameters of age (6/33), sex (3/33) and stage (3/27) in the cancers studied, the results of the survival analysis reflect the pan-cancer prognostic value of ALKBH7. In addition, ALKBH7 expression was significantly correlated with the TMB (7/33), MSI (13/33), mDNAsi (12/33) and mRNAsi (13/33) in human cancers. Moreover, ALKBH7 expression was associated and predominantly negatively correlated with the expression of immune checkpoint (ICP) genes in many cancers. Furthermore, ALKBH7 correlated with infiltrating immune cells and ESTIMATE scores, especially in PAAD, PRAD and THCA. Finally, the ALKBH7 gene coexpression network is involved in the regulation of cellular immune, oxidative, phosphorylation, and metabolic pathways. In conclusion, ALKBH7 may serve as a potential prognostic pan-cancer biomarker and is involved in the immune response. Our pan-cancer analysis provides insight into the role of ALKBH7 in different cancers.Background Mainstream application of cancer immunotherapy is hampered by the low response rate of most cancer patients. A novel immunotherapeutic target or a biomarker predicting response to immunotherapy needs to be developed. Guanylate-binding protein 1 (GBP1) is an interferon (IFN)-inducible guanosine triphosphatases (GTPases) involving inflammation and infection. However, the immunological effects of GBP1 in pan-cancer patients are still obscure. Methods Using large-scale public data, we delineated the landscape of GBP1 across 33 cancer types. The correlation between GBP1 expression or mutation and immune cell infiltration was estimated by ESTIMATE, TIMER, xCell, and quanTIseq algorithms. GBP1-related genes and proteins were subjected to function enrichment analysis. Clustering analysis explored the relationship between GBP1 expression and anti-tumor immune phenotypes. We assessed the patient's response to immunotherapy using the tumor immune dysfunction and exclusion (TIDE) score and immunophenoscore (IPt [area under the curve (AUC) 0.813], the IMvigor210 cohort (AUC 0.607), the Lauss et al. cohort (AUC 0.740), and the Kim et al. cohort (AUC 0.793). Conclusion This study provides comprehensive insights into the role of GBP1 in a pan-cancer manner. We identify GBP1 expression as a predictive biomarker for immunotherapy, potentially enabling more precise and personalized immunotherapeutic strategies in the future.Pluripotency is a transient state in early embryos, which is regulated by an interconnected network of pluripotency-related genes. The pluripotent state itself seems to be highly dynamic, which leads to significant differences in the description of induced pluripotent stem cells from different species at the molecular level. With the application of cell reprogramming technology in fish, the establishment of a set of molecular standards for defining pluripotency will be important for the research and potential application of induced pluripotent stem cells in fish. In this study, by BLAST search and expression pattern analysis, we screen out four pluripotent genes (Oct4, Nanog, Tdgf1, and Gdf3) in zebrafish (Danio rerio) and crucian carp (Carassius). These genes were highly expressed in the short period of early embryonic development, but significantly down-regulated after differentiation. Moreover, three genes (Oct4, Nanog and Tdgf1) have been verified that are suitable for identifying the pluripotency of induced pluripotent stem cells in zebrafish and crucian carp. Our study expands the understanding of the pluripotent markers of induced pluripotent stem cells in fish.Chronic intermittent hypoxia (CIH) is the main feature of obstructive sleep apnea (OSA) and is known to exaggerate cardiac remodeling after myocardial infarction (MI). However, the specific contribution of CIH to overall OSA-induced pathological complications and the transcriptomic mechanisms underlying CIH-exaggerated post-MI remodeling remains unclear. In this study, we used RNA-sequencing to construct the expression profiles of cardiac mRNAs, microRNAs, and long non-coding RNAs (lncRNA) in four groups of C57BL/6J mice (Sham, CIH, MI, MI + CIH) to evaluate how CIH regulates cardiac remodeling after MI. Compared with the other three groups, the MI + CIH group exhibited 345 lncRNAs, 35 microRNAs, and 5,220 differentially expressed mRNAs. Further analysis showed that CIH led to significant changes in Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of the differentially expressed mRNAs. Co-expression network analysis identified two core lncRNAs (Mirt1 and AC125351.1) and two core microRNAs (miR-466i-5p and miR-574-5p) during the development of CIH-exaggerated post-MI remodeling, and they were verified by quantitative real-time PCR (qRT-PCR). LncRNA-mRNA correlation analysis further showed that lncRNA Mirt1 was positively correlated with Apbb1ip and Lcp2. In addition, microRNA-mRNA correlation analysis showed that microRNA miR-466i-5p was positively correlated with Snai2, Cdc27, and Ngfr. Furthermore, combining with lncRNA-mRNA and miRNA-mRNA networks, 44 RNAs were identified in the competitive endogenous RNA (ceRNA) network. Mirt1 acts as a ceRNA to bind to miR-466i-5p to further regulate the expression levels of the target gene, thereby aggravating cardiac remodeling after MI. In conclusion, our study provides a systematic perspective on the potential functions of mRNAs, microRNAs, and lncRNAs in CIH-exaggerated post-MI cardiac remodeling. Our data suggest that lncRNA Mirt1 may be the most critical regulator of MI aggravated by CIH.Studies have found that pathogenic fungi and plants have sRNA transboundary regulation mechanisms. However, no researchers have used computer methods to carry out comprehensive studies on whether there is a more remarkable similarity in the transboundary regulation of plants by pathogenic fungi. In this direction, high-throughput non-coding sRNA data of three types of fungi and fungi-infected plants for 72 h were obtained. These include the Magnaporthe, Magnaporthe oryzae infecting Oryza sativa, Botrytis cinerea, Botrytis cinerea infecting Solanum lycopersicum, Phytophthora infestans and Phytophthora infestans infecting Solanum tuberosum. Research on these data to explore the commonness of fungal sRNA transboundary regulation of plants. First, using the big data statistical analysis method, the sRNA whose expression level increased significantly after infection was found as the key sRNA for pathogenicity, including 355 species of Magnaporthe oryzae, 399 species of Botrytis cinerea, and 426 species of Phytophtt each model performed well. Among them, XGBoost performed very well in the five models, and the AUC of the validation set was 0.86, 0.93, and 0.90. Therefore, this model has a reference value for predicting other fungi's key sRNAs that transboundary regulation of plants.The regulatory relationships between genes and proteins in a cell form a gene regulatory network (GRN) that controls the cellular response to changes in the environment. A number of inference methods to reverse engineer the original GRN from large-scale expression data have recently been developed. However, the absence of ground-truth GRNs when evaluating the performance makes realistic simulations of GRNs necessary. One aspect of this is that local network motif analysis of real GRNs indicates that the feed-forward loop (FFL) is significantly enriched. To simulate this properly, we developed a novel motif-based preferential attachment algorithm, FFLatt, which outperformed the popular GeneNetWeaver network generation tool in reproducing the FFL motif occurrence observed in literature-based biological GRNs. It also preserves important topological properties such as scale-free topology, sparsity, and average in/out-degree per node. We conclude that FFLatt is well-suited as a network generation module for a benchmarking framework with the aim to provide fair and robust performance evaluation of GRN inference methods.Objective To investigate the effects of genetic polymorphisms of human nicotinic acetylcholine receptor subunits α3, α4 and α5, which are encoded by CHRNA3, CHRNA4 CHRNA5 genes, respectively, on nicotine addiction and outcomes of pharmacological treatments for smoking cessation. Methods A total of 143 smokers and 130 non-smokers were included. Genotyping for CHRNA3 rs578776, CHRNA4 rs1044396-rs1044397, CNRNA5 rs16969968 polymorphisms was performed by PCR, flowed by RFLP. Clinical outcomes and success rates of pharmacological treatments for smoking cessation with nicotine replacement therapy (NRT), bupropion or varenicline were determined at the 12th week of the treatment. Results Overall, 52 out of 143 (36.4%) smokers who received pharmacotherapy were able to quit smoking. Success rates for smoking cessation were similar for female (30.3%) and male (41.6%) subjects (p = 0.16). The success rate for smoking cessation treatment with varenicline (58.5%) was significantly higher as compared to other treatments with NRT (20.0%), bupropion (32.3%) or bupropion + NRT (40.0%) (chi-square test, p = 0.001). Smoker vs. non-smoker status and the clinical outcomes of drugs used for smoking cessation were found similar in subjects carrying wild-type and variant alleles of human nicotinic acetylcholine receptor α subunits. Conclusion In this study, smoking cessation treatment with varenicline was significantly more effective than treatments with nicotine replacement or bupropion in a cohort of Turkish subjects. Smoker/non-smoker status and the clinical outcomes of treatment with pharmacological agents were similar in subjects with wild-type or variant alleles for human nicotinic acetylcholine receptor subunits α3 (CHRNA3), α4 (CHRNA4) and α5 (CHRNA5).