Tailoring Camelina Seed Fatty Acid Composition via Fast Neutron Mutagenesis

Despite its minor status as an oilseed, Camelina sativa is a crop with the potential to reach greater levels of production in Canada due to its unique seed oil composition, relatively low input requirements, and availability of both spring and winter varieties. The limited genetic diversity of the species presents a challenge for camelina improvement through breeding. The aim of this study was to induce genetic variations in camelina’s genome through Fast Neutron (FN) irradiation applied to seeds in a dose gradient ranging from 7.1 to 49.5 Gy. A range of mutations should be caused following FN irradiation including deletions, point mutations, and rearrangements due to DNA damage and subsequent repair. In germination assays of FN-irradiated seeds, FN irradiation had no impact on germination, but higher doses of irradiation resulted in plants with a slower maturity. A FN mutagenesis population was established from irradiated camelina seeds for phenotypic and genotypic characterization. Male sterility and toothed leaf margin of irradiated camelina were observed based on visual observations. Seed fatty acids were analyzed and lineages with altered fatty acid composition, such as high C18:3 and low C20:1, were identified. To study novel genotypes, genotyping by sequencing was applied. An approach was designed and implemented that utilized Illumina sequence technology for generating large amounts of genome sequence data, in conjunction with Oxford Nanopore Technologies (ONT) sequencing for validation. One mutant lineage FN49-38 was characterized whose total very long chain fatty acid composition was 19.6%, a relatively lower percentage than of wild type (23.9%). This lineage carried a genomic DNA deletion of approximately 1.2kb spanning the 5' UTR (untranslated region) and the front half of the FAE1B-ORF (open reading frame) detected through Illumina sequencing, which was validated by ONT sequencing. Furthermore, the accuracy and authenticity of the deletion were confirmed by Sanger sequencing of the cloned mutant gene amplified by PCR (polymerase chain reaction) using specific primers flanking the mutated region. The ONT data was used to review and correct the current annotation of the FAE1 gene on chromosomes 11 and 12. A backcrossing experiment was conducted and confirmed that the deletion was linked to the reduced very long chain fatty acid composition phenotype

Clinical phenotype and genotype of children with GABAA receptor α1 subunit gene-related epilepsy

ObjectiveThis study aimed to summarize the clinical phenotype and genotype of children with epilepsy caused by GABRA1 gene variants.MethodsEight epilepsy patients, who were admitted to Qilu Hospital of Shandong University from 2015 to 2021, were enrolled in the study. GABRA1 gene variants were detected by whole-exome sequencing. Epilepsy clinical manifestations, electroencephalography, neuroimaging characteristics and treatment methods were retrospectively analyzed.ResultsAmong the eight patients, four were males and four were females. Epilepsy onset age was between 3 and 8 months of age. Two patients had a family history of epilepsy. Six cases were de novo variants, and two were hereditary variants. Two children carried the same pathogenic variants, and five carried novel pathogenic variants that had not been reported internationally. The types of seizures were diverse, including focal seizures in five cases, generalized tonic-clonic seizures in five cases, and spasms in two cases. Electroencephalography of seven cases showed abnormal background rhythms, and six cases showed abnormal discharge during the interictal period. No obvious abnormalities were found on magnetic resonance imaging in five cases. All eight children had different degrees of developmental retardation.ConclusionDe novo pathogenic variants in GABRA1 are more common than inherited pathogenic variants, and most epilepsy symptoms begin in the first year of life, manifesting with a variety of seizure types and developmental delays. Conventional treatment usually involves one or more drugs; although drug treatment can control seizures in some cases, cognitive and developmental deficits often exist. The five newly discovered pathogenic variants enrich the GABRA1 gene pathogenic variant spectrum

Credit risk prediction for small and medium enterprises utilizing adjacent enterprise data and a relational graph attention network

Credit risk prediction for small and medium enterprises (SMEs) has long posed a complex research challenge. Traditional approaches have primarily focused on enterprise-specific variables, but these models often prove inadequate when applied to SMEs with incomplete data. In this innovative study, we push the theoretical boundaries by leveraging data from adjacent enterprises to address the issue of data deficiency. Our strategy involves constructing an intricate network that interconnects enterprises based on shared managerial teams and business interactions. Within this network, we propose a novel relational graph attention network (RGAT) algorithm capable of capturing the inherent complexity in its topological information. By doing so, our model enhances financial service providers' ability to predict credit risk even in the face of incomplete data from target SMEs. Empirical experiments conducted using China's SMEs highlight the predictive proficiency and potential economic benefits of our proposed model. Our approach offers a comprehensive and nuanced perspective on credit risk while demonstrating the advantages of incorporating network-wide data in credit risk prediction

Role of CTSC in Glioblastoma Based on Oncomine and TCGA Database

Background and objective Glioblastoma (GBM) is one of the malignant tumors causing death worldwide. Most patients were found in the middle and late stages and had poor prognosis. The purpose of this study was to investigate the expression and significance of CTSC in GBM. Methods The information about CTSC in Oncomine database was collected and analyzed twice. The role of CTSC in GBM was meta-analyzed. The expression of CTSC in glioma cell lines was retrieved by CCLE database, and the survival of patients was analyzed by TCGA database. Results A total of 1,459 different types of CTSC were collected in Oncomine database, 134 of which had statistical differences in CTSC expression, 89 of which had increased CTSC expression and 45 of which had decreased CTSC expression. A total of 50 studies involving the expression of CTSC in GBM cancer and normal tissues included 1,189 samples. Compared with the control group, CTSC was highly expressed in GBM (P < 0.05). Moreover, CTSC was highly expressed in glioma cell lines. There was a correlation between the expression of CTSC and the overall survival rate of GBM. The overall survival rate of patients with high expression of CTSC was worse, while the prognosis of patients with low expression of SPC24 was better (P < 0.05). Conclusion Through the in-depth mining of oncomine gene chip database, we propose that CTSC is highly expressed in GBM tissues and is related to the prognosis of GBM, which may provide an important theoretical basis for the treatment of glioma

Enrofloxacin Induces Intestinal Microbiota-Mediated Immunosuppression in Zebrafish

The immunosuppressive effects of antibiotics and the potential associations with the intestinal microbiota of the host have been increasingly recognized in recent years. However, the detailed underlying mechanisms of immune interference of antibiotics in environmental organisms remain unclear, particularly at the early life stage of high sensitivity. To better understand the gut microbiome and immune function interactions, the vertebrate model, zebrafish, was treated with environmentally relevant concentrations of a frequently detected antibiotic, enrofloxacin (ENR), ranging from 0.01 to 100 μg/L. 16S ribosomal RNA sequencing indicated diminished diversity, richness, and evenness of intestinal flora following ENR treatment. Twenty-two taxa of gut bacteria including Rickettsiales, Pseudomonadales, and Flavobacteriales were significantly correlated with immunosuppressive biomarkers, including a significant decrease in the abundance of macrophages and neutrophils. To validate the immunomodulatory effects due to altered intestinal microbial populations, zebrafish reared under sterile and non-sterile husbandry conditions were compared after ENR treatment. A significant inhibitory effect was induced by ENR treatment under non-sterile conditions, while the number of macrophages and neutrophils, as well as biomarkers of immunosuppressive effects, were significantly salved in zebrafish under sterile conditions, confirming for the first time that immunosuppression by ENR was closely mediated through alterations of the intestinal microbiome in fish.publishedVersio

Global stability and optimal vaccination control of SVIR models

Vaccination is widely acknowledged as an affordable and cost-effective approach to guard against infectious diseases. It is important to take vaccination rate, vaccine effectiveness, and vaccine-induced immune decline into account in epidemic dynamical modeling. In this paper, an epidemic dynamical model of vaccination is developed. This model provides a framework of the infectious disease transmission dynamics model through qualitative and quantitative analysis. The result shows that the system may have multiple equilibria. We used the next-generation operator approach to calculate the maximum spectral radius, that is, basic reproduction number ${R_{vac}}$. Next, by dividing the model into infected and uninfected subjects, we can prove that the disease-free equilibrium is globally asymptotically stable when {R_{vac}} < 1 , provided certain assumptions are satisfied. When {R_{vac}} > 1 , there exists a unique endemic equilibrium. Using geometric methods, we calculate the second compound matrix and demonstrate the Lozinskii measure $\bar q \leqslant 0$, which is equivalent to the unique endemic equilibrium, which is globally asymptotically stable. Then, using center manifold theory, we justify the existence of forward bifurcation. As the vaccination rate decreases, the likelihood of forward bifurcation increases. We also theoretically show the presence of Hopf bifurcation. Then, we performed sensitivity analysis and found that increasing the vaccine effectiveness rate can curb the propagation of disease effectively. To examine the influence of vaccination on disease control, we chose the vaccination rate as the optimal vaccination control parameter, using the Pontryagin maximum principle, and we found that increasing vaccination rates reduces the number of infected individuals. Finally, we ran a numerical simulation to finalize the theoretical results