Byerschurch2360

Background Colon cancer is a common malignant tumor with poor prognosis. The aim of this study is to explore the immune-related prognostic signatures and the tumor immune microenvironment of colon cancer. Methods The mRNA expression data of TCGA-COAD from the UCSC Xena platform and the list of immune-related genes (IRGs) from the ImmPort database were used to identify immune-related differentially expressed genes (DEGs). Then, we constructed an immune-related risk score prognostic model and validated its predictive performance in the test dataset, the whole dataset, and two independent GEO datasets. In addition, we explored the differences in tumor-infiltrating immune cell types, tumor mutation burden (TMB), microsatellite status, and expression levels of immune checkpoints and their ligands between the high-risk and low-risk score groups. Moreover, the potential value of the identified immune-related signature with respect to immunotherapy was investigated based on an immunotherapeutic cohort (Imvigor210) tr3; GSE17536 p = 0.0008; immunotherapeutic cohort without platinum treatment p = 0.0014; immunotherapeutic cohort with platinum treatment p = 0.0027). Conclusion We developed a robust immune-related prognostic signature that performed great in multiple cohorts and explored the characteristics of the tumor immune microenvironment of colon cancer patients, which may give suggestions for the prognosis and immunotherapy in the future.The objective of the present study was to quantify the association between both pedigree and genome-based measures of global heterozygosity and carcass traits, and to identify single nucleotide polymorphisms (SNPs) exhibiting non-additive associations with these traits. The carcass traits of interest were carcass weight (CW), carcass conformation (CC) and carcass fat (CF). Dynasore To define the genome-based measures of heterozygosity, and to quantify the non-additive associations between SNPs and the carcass traits, imputed, high-density genotype data, comprising of 619,158 SNPs, from 27,213 cattle were used. The correlations between the pedigree-based heterosis coefficient and the three defined genomic measures of heterozygosity ranged from 0.18 to 0.76. The associations between the different measures of heterozygosity and the carcass traits were biologically small, with positive associations for CW and CC, and negative associations for CF. Furthermore, even after accounting for the pedigree-based heterosis coefficient of an animal, part of the remaining variability in some of the carcass traits could be captured by a genomic heterozygosity measure. This signifies that the inclusion of both a heterosis coefficient based on pedigree information and a genome-based measure of heterozygosity could be beneficial to limiting bias in predicting additive genetic merit. Finally, one SNP located on Bos taurus (BTA) chromosome number 5 demonstrated a non-additive association with CW. Furthermore, 182 SNPs (180 SNPs on BTA 2 and two SNPs on BTA 21) demonstrated a non-additive association with CC, while 231 SNPs located on BTA 2, 5, 11, 13, 14, 18, 19 and 21 demonstrated a non-additive association with CF. Results demonstrate that heterozygosity both at a global level and at the level of individual loci contribute little to the variability in carcass merit.Objective To identify CT imaging biomarkers based on radiomic features for predicting brain metastases (BM) in patients with ALK-rearranged non-small cell lung cancer (NSCLC). Methods NSCLC patients with pathologically confirmed ALK rearrangement from January 2014 to December 2020 in our hospital were enrolled retrospectively in this study. Finally, 77 patients were included according to the inclusion and exclusion criteria. Patients were divided into two groups BM+ were those patients who were diagnosed with BM at baseline examination (n = 16) or within 1 year's follow-up (n = 14), and BM- were those without BM followed up for at least 1 year (n = 47). Radiomic features were extracted from the pretreatment thoracic CT images. Sequential univariate logistic regression, LASSO regression, and backward stepwise logistic regression were used to select radiomic features and develop a BM-predicting model. Results Five robust radiomic features were found to be independent predictors of BM. AUC for radiomics model was 0.828 (95% CI 0.736-0.921), and when combined with clinical features, the AUC was increased (p = 0.017) to 0.909 (95% CI 0.845-0.972). The individualized BM-predicting model incorporated with clinical features was visualized by the nomogram. Conclusion Radiomic features extracted from pretreatment thoracic CT images have the potential to predict BM within 1 year after detection of the primary tumor in patients with ALK-rearranged NSCLC. The radiomics model incorporated with clinical features shows improved risk stratification for such patients.Seed size/weight is a multigenic trait that is governed by complex transcriptional regulatory pathways. An understanding of the genetic basis of seed size is of great interest in the improvement of seed yield and quality in oilseed crops. A global transcriptome analysis was performed at the initial stages of seed development in two lines of Brassica juncea, small-seeded EH-2 and large-seeded PJ. The anatomical analyses revealed significant differences in cell number and cell size in the outer layer of the seed coat between EH-2 and PJ. Pairwise comparisons at each developmental stage identified 5,974 differentially expressed genes (DEGs) between the two lines, of which 954 genes belong to different families of transcription factors. Two modules were found to be significantly correlated with an increased seed size using weighted gene coexpression network analysis. The DEG and coexpression datasets were integrated with the thousand seed weight (Tsw) quantitative trait loci (QTL) mapped earlier in the EPJ (EH-2 × PJ) doubled haploid (DH) population, which identified forty potential key components controlling seed size. The candidate genes included genes regulating the cell cycle, cell wall biogenesis/modification, solute/sugar transport, and hormone signaling. The results provide a valuable resource to widen the current understanding of regulatory mechanisms underlying seed size in B. juncea.Over the last decades, numerous examples have involved nuclear non-coding RNAs (ncRNAs) in the regulation of gene expression. ncRNAs can interact with the genome by forming non-canonical nucleic acid structures such as R-loops or DNARNA triplexes. They bind chromatin and DNA modifiers and transcription factors and favor or prevent their targeting to specific DNA sequences and regulate gene expression of diverse genes. We review the function of these non-canonical nucleic acid structures in regulating gene expression of multicellular organisms during development and in response to different stress conditions and DNA damage using examples described in several organisms, from plants to humans. We also overview recent techniques developed to study where R-loops or DNARNA triplexes are formed in the genome and their interaction with proteins.Spinal cord injury (SCI) and ankylosing spondylitis (AS) are common inflammatory diseases in spine surgery. However, it is a project where the relationship between the two diseases is ambiguous and the efficiency of drug discovery is limited. Therefore, the study aimed to investigate new drug therapies for SCI and AS. First, text mining was used to obtain the interacting genes related to SCI and AS, and then, the functional analysis was conducted. Protein-protein interaction (PPI) networks were constructed by STRING online and Cytoscape software to identify hub genes. Last, hub genes and potential drugs were performed after undergoing drug-gene interaction analysis, and MicroRNA and transcription factors regulatory networks were also analyzed. Two hundred five genes common to "SCI" and "AS" identified by text mining were enriched in inflammatory responses. PPI network analysis showed that 30 genes constructed two significant modules. Ultimately, nine (SST, VWF, IL1B, IL6, CXCR4, VEGFA, SERPINE1, FN1, and PROS1) out of 30 genes could be targetable by a total of 13 drugs. In conclusion, the novel core genes contribute to a novel insight for latent functional mechanisms and present potential prognostic indicators and therapeutic targets in SCI and AS.The mitochondrial DNA (mtDNA) has been used to trace population evolution and apply to forensic identification due to the characteristics including lack of recombination, higher copy number and matrilineal inheritance comparing with nuclear genome DNA. In this study, mtDNA control region sequences of 91 Kirgiz individuals from the Northwest region of China were sequenced to identify genetic polymorphisms and gain insight into the genetic background of the Kirgiz ethnic group. MtDNA control region sequences of Kirgiz individuals presented relatively high genetic polymorphisms. The 1,122 bp sequences of mtDNA control region could differ among unrelated Kirgiz individuals, which suggested the mtDNA control region sequences have a good maternal pedigree tracing capability among different Kirgiz individuals. The neutrality test, mismatch distribution, Bayesian phylogenetic inference, Bayesian skyline analysis, and the median network analyses showed that the Kirgiz group might occurred population expansion, and the expansion could be observed at about ∼53.41 kilo years ago (kya) when ancestries of modern humans began to thrive in Eurasia. The pairwise population comparisons, principal component analyses, and median network analyses were performed based on haplogroup frequencies or mtDNA control region sequences of 5,886 individuals from the Kirgiz group and the 48 reference populations all over the world. And the most homologous haplotypes were found between Kirgiz individuals and the East Asian individuals, which indicated that the Kirgiz group might have gene exchanges with the East Asian populations.Autosomal recessive cerebellar ataxia type 1 (ARCA-1), also known as autosomal recessive spinocerebellar ataxia type 8 (SCAR8), is caused by spectrin repeat containing nuclear envelope protein 1 (SYNE1) gene mutation. Nesprin-1, encoded by SYNE1, is widely expressed in various tissues, especially in the striated muscle and cerebellum. The destruction of Nesprin-1 is related to neuronal and neuromuscular lesions. It has been reported that SYNE1 gene variation is associated with Emery-Dreifuss muscular dystrophy type 4, arthrogryposis multiplex congenita, SCAR8, and dilated cardiomyopathy. The clinical manifestations of SCAR8 are mainly characterized by relatively pure cerebellar ataxia and may be accompanied by upper and/or lower motor neuron dysfunction. Some affected people may also display cerebellar cognitive affective syndrome. It is conventionally held that the age at the onset of SCAR8 is between 6 and 42 years (the median age is 17 years). Here, we report a pedigree with SCAR8 where the onset age in the proband is 48 years. This case report extends the genetic profile and clinical features of SCAR8. A new pathogenic site (c.7578del; p.S2526Sfs*8) located in SYNE1, which is the genetic cause of the patient, was identified via whole exome sequencing (WES).