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Abstract Background Lupus nephritis (LN) is the most common cause of kidney injury in systemic lupus erythematosus (SLE) patients and is associated with increased mortality. DNA methylation, one of the most important epigenetic modifications, has been reported as a key player in the pathogenesis of SLE. Hence, our article aimed to explore DNA methylation in CD4+ T cells from LNs to identify additional potential biomarkers and pathogenic genes involved in the progression of LN. Methods Our study enrolled 46 SLE patients with or without kidney injury and 23 healthy controls from 2019 to 2022. CD4+ T cells were sorted for DNA methylation genotyping and RNA-seq. Through bioinformatics analysis, we identified the significant differentially methylated CpG positions (DMPs) only in the LN group and validated them by Bisulfite PCR. Integration analysis was used to screen for differentially methylated and expressed genes that might be involved in the progression of LN, and the results were analyzed via cell experiments and flow cytometry. Results We identified 243 hypomethylated sites and 778 hypermethylated sites only in the LN cohort. Three of these DMPs, cg08332381, cg03297029, and cg16797344, were validated by Bisulfite PCR and could be potential biomarkers for LN. Integrated analysis revealed that the expression of BCL2L14 and IFI27 was regulated by DNA methylation, which was validated by azacytidine (5-aza) treatment. The overexpression of BCL2L14 in CD4+ T cells might induce renal fibrosis and inflammation by regulating the differentiation and function of Tfh cells. Conclusion Our study identified novel aberrant DMPs in CD4+ T cells only in LN patients and DNA methylation-regulated genes that could be potential LN biomarkers. BCL2L14 is likely involved in the progression of LN and might be a treatment target.

Lactoferrin is an iron-binding glycoprotein with antibacterial, antitumor, and immunomodulatory functions derived from milk and mucosal secretions. Lactoferrin is used in various products, such as infant formula milk powder, nutritional supplements, and cosmetics. Researchers have developed new technologies to produce lactoferrin because there are limitations in the separation and purification of lactoferrin from milk that cannot compensate for the market demand. Therefore, synthetic systems of lactoferrin have been developed with the development of genetic engineering, and the structure of lactoferrin expressed in heterologous systems is very similar to that of natural lactoferrin. The structure and functions of lactoferrin and the design and construction of synthetic lactoferrin biological systems, especially microbial synthetic systems, including prokaryotic and eukaryotic host-expression systems, are described. On the basis of these results, we summarize the challenges and solutions for constructing systems of high-yield lactoferrin. The development directions of recombinant lactoferrin are discussed in this review. Overall, the design and development of these synthetic biological systems have allowed us to explore the great potential of the industrial large-scale preparation of lactoferrin.

Growth is an important trait in aquaculture that is influenced by various factors, among which genetic regulation plays a crucial role. Megalobrama amblycephala, one of the most important freshwater species in China, exhibits wide variations in body mass among individuals of the same age within the same pool. But the molecular mechanisms underlying wide variation in body mass remain unclear. Here, we performed muscle histological and transcriptome analysis of muscle tissues from Fast-Growing (FG) and Slow-Growing (SG) M. amblycephala at the age of 4 months old (4 mo) and 10 months old (10 mo) to elucidate its muscle development and growth mechanism. The muscle histological analysis showed smaller diameter and higher total number of muscle fibers in FG compared to SG at 4 mo, while larger diameter and total number of muscle fibers were detected in FG at 10 mo. The transcriptome analysis of muscle tissue detected 1171 differentially expressed genes (DEGs) between FG and SG at 4 mo, and 718 DEGs between FG and SG at 10 mo. Furthermore, 44 DEGs were consistently up-regulated in FG at both 4 mo and 10 mo. Up-regulated DEGs in FG at 4 mo were mainly enriched in the pathways related to cell proliferation, while down-regulated DEGs were significantly enriched in cell fusion and muscle contraction. Up-regulated DEGs in FG at 10 mo were mainly enriched in the pathways related to cell proliferation and protein synthesis. Therefore, these results provide novel insights into the molecular mechanism of M. amblycephala muscle growth at different stages, and will be of great guiding significance to promote the fast growth of M. amblycephala.

We report a case of myeloproliferative neoplasm, not otherwise specified (MPN-NOS)-transformed AML with BCR::JAK2 rearrangement. Chromosomal analysis indicated a simple abnormal karyotype 46,XY,t(7;17)(q21;q24),t(9;22)(p24;q11.2). Fluorescence in situ hybridization (FISH) using a BCR/ABL1/ASS1 probe set suggested a possible BCR rearrangement and a reflex JAK2 breakapart probe indicated JAK2 rearrangement, most likely partnered with BCR. Optical genome mapping (OGM) analysis confirmed BCR::JAK2 derived through an inv(9)(p24p13) after a t(9;22)(p13;q11.2) in this case. Due to the complexity of chromosomal aberrations, disruption and/or rearrangement of other genes such as KIF24::BCR, JAK2::KIF24/UBAP1, and CDK6:SOX9 were also identified by OGM. Although the functionality and clinical importance of these novel rearrangements were unknown, disruption of these genes might be associated with a poorer response to chemotherapy and disease progression. We also reviewed all cases with BCR::JAK2 rearrangement reported in the literature. In conclusion, a suspected t(9;22)/BCR::JAK2 rearrangement warrants further characterization with genomic assays such as OGM, whole chromosome sequencing, and RNA sequencing to explore other gene disruptions and/or rearrangements.

Abstract Background Ancestry informative markers are regarded as useful tools for inferring the ancestral information of an individual, which have been widely used in the criminal investigations and population genetic studies. Previously, a multiplex amplification panel containing 39 AIM-InDel loci was constructed. This study aims to investigate the genetic polymorphisms of these 39 AIM-InDel loci in Yunnan Hani and Miao ethnic groups, and to uncover their genetic affinities with reference populations based on the AIM-InDel markers. Materials and methods In this research, 39 AIM-InDel profiles of 203 unrelated Miao individuals and 203 unrelated Hani individuals in Yunnan province of China were acquired. Additionally, we evaluated the genetic polymorphisms of 39 InDel loci in Yunnan Miao and Hani groups. Moreover, the genetic relationships among Yunnan Miao, Hani and reference populations were also clarified based on Nei’s genetic distances, pairwise fixation indexes, principal component analyses, phylogenetic analyses, and STRUCTURE analyses. Results Genetic diversity analyses demonstrated that these InDel loci showed varying degrees of genetic polymorphisms, and could be utilized in forensic identifications in Yunnan Miao and Hani groups. The results of principal component analyses, phylogenetic analyses and Structure analyses revealed that Yunnan Miao and Hani groups had closer genetic relationships with East Asian populations, especially with the populations from Southern China. This research enriched the genetic data of Chinese ethnic minority, and provided ancestral information of Yunnan Miao and Hani groups from the perspective of population genetics.

Introduction: Cuproptosis seems to promote the progression of diverse diseases. Hence, we explored the cuproptosis regulators in human spermatogenic dysfunction (SD), analyzed the condition of immune cell infiltration, and constructed a predictive model.Methods: Two microarray datasets (GSE4797 and GSE45885) related to male infertility (MI) patients with SD were downloaded from the Gene Expression Omnibus (GEO) database. We utilized the GSE4797 dataset to obtain differentially expressed cuproptosis-related genes (deCRGs) between SD and normal controls. The correlation between deCRGs and immune cell infiltration status was analyzed. We also explored the molecular clusters of CRGs and the status of immune cell infiltration. Notably, weighted gene co-expression network analysis (WGCNA) was used to identify the cluster-specific differentially expressed genes (DEGs). Moreso, gene set variation analysis (GSVA) was performed to annotate the enriched genes. Subsequently, we selected an optimal machine-learning model from four models. Finally, nomograms, calibration curves, decision curve analysis (DCA), and the GSE45885 dataset were utilized to verify the predictions’ accuracy.Results: Among SD and normal controls, we confirmed that there are deCRGs and activated immune responses. Through the GSE4797 dataset, we obtained 11 deCRGs. ATP7A, ATP7B, SLC31A1, FDX1, PDHA1, PDHB, GLS, CDKN2A, DBT, and GCSH were highly expressed in testicular tissues with SD, whereas LIAS was lowly expressed. Additionally, two clusters were identified in SD. Immune-infiltration analysis showed the existing heterogeneity of immunity at these two clusters. Cuproptosis-related molecular Cluster2 was marked by enhanced expressions of ATP7A, SLC31A1, PDHA1, PDHB, CDKN2A, DBT, and higher proportions of resting memory CD4+ T cells. Furthermore, an eXtreme Gradient Boosting (XGB) model based on 5-gene was built, which showed superior performance on the external validation dataset GSE45885 (AUC = 0.812). Therefore, the combined nomogram, calibration curve, and DCA results demonstrated the accuracy of predicting SD.Conclusion: Our study preliminarily illustrates the relationship between SD and cuproptosis. Moreover, a bright predictive model was developed.

AbstractFlavonoids are rich in tea plants (Camellia sinensis

Single nucleotide polymorphism (SNP) possesses a promising application in forensic individual identification due to its wide distribution in the human genome and the ability to carry out the genotyping of degraded biological samples by designing short amplicons. Some commonly used individual identification SNPs are less polymorphic in East Asian populations. In order to improve the individual identification efficiencies in East Asian populations, SNP genetic markers with relatively higher polymorphisms were selected from the 1,000 Genome Project phase III database in East Asian populations. A total of 111 individual identification SNPs (II-SNPs) with the observed heterozygosity values greater than 0.4 were screened in East Asian populations, and then, the forensic efficiencies of these selected SNPs were also evaluated in Chinese Inner Mongolia Manchu group. The observed heterozygosity and power of discrimination values at 111 II-SNPs in the Inner Mongolia Manchu group ranged from 0.4011 to 0.7005, and 0.5620 to 0.8025, respectively, and the average value of polymorphism information content was greater than 0.3978. The cumulative match probability and combined probability of exclusion values at II-SNPs were 7.447E-51 and 1-4.17E-12 in the Inner Mongolia Manchu group, respectively. The accumulative efficiency results indicated that the set of II-SNPs could be used as a potential tool for forensic individual identification and parentage testing in the Manchu group. The sequencing depths ranged from 781× to 12374×. And the mean allele count ratio and noise level were 0.8672 and 0.0041, respectively. The sequencing results indicated that the SNP genetic marker detection based on the massively parallel sequencing technology for SNP genetic markers had high sequencing performance and could meet the sequencing requirements of II-SNPs in the studied group.

Astragalus membranaceus, as an important medicinal plant, are an excellent source of flavonoids. Flavonoid compounds in A. membranaceus have been widely used in medicine and supplement, but known of the molecular mechanism of flavonoid biosynthesis is still very few. Here, we analyzed the association between flavonoid content and gene expression pattern during six different fruit developmental stages. Sixteen gene expression trends were significantly identified, involving 8,218 genes. The gene expression trend in profile 0 was positively correlated with flavonoid content, while the gene expression trend in profile 79 was negatively correlated with flavonoid content at six developmental stages. The expression level of genes involved in the general phenylpropane pathway was higher than that of genes involved in the flavonoid biosynthesis pathway. A total of 37 genes involved in flavonoid synthesis were identified in A. membranaceus. The expression pattern of flavonoid-related genes was highly correlated with flavonoid content. Our study deepened the understanding of the flavonoid synthesis mechanism and provided useful resources for future studies on the high flavonoid molecular breeding of A. membranaceus.

The mud crab, Scylla paramamosain, has abundant nutrients in its edible parts, ovary, hepatopancreas, and muscle during the ovarian maturation stage. The ovary of S. paramamosain can re-mature after spawning during the secondary ovarian maturation period. We aimed to analyze the characteristics of the first vitellogenesis period (FVP)1 and second vitellogenesis period (SVP)2 of S. paramamosain during ovarian maturation to understand the differences in vitellogenesis patterns between the first and second ovarian maturation periods. Accordingly, the gonadosomatic index (GSI) and hepatopancreatic index (HSI), the external and histological characteristics of the ovary and hepatopancreas, the Sp-Vg (vitellogenin, Vg) expression levels in the hepatopancreas and ovary, and the dynamics of the biochemical components in the ovary, hepatopancreas, and muscle were determined. Based on the results, the GSI was significantly positively correlated with HSI during the FVP and significantly negatively correlated with HSI from stage Ⅳ to stage Ⅴ of the SVP. A significant difference was found between the FVP and SVP in the hepatopancreas. Notably, the hepatopancreas displayed a gradual degeneration trend during the SVP. The expression level of Sp-Vg was significantly higher in the hepatopancreas than that in the ovary during the FVP and SVP. Seventeen amino acids were detected in the hepatopancreas, ovary, and muscle during the FVP and SVP, with glutamate as the predominant amino acid. During the FVP and SVP, the C16:0 and C18:1n9c were the dominant fatty acids in the hepatopancreas and ovary, the MUFA gradually increased in the ovary and hepatopancreas, and a significant difference was found in the dynamic trend of the HUFA and SFA contents from stage Ⅳ to stage Ⅴ between the FVP and SVP. These findings indicate that the ovary can re-mature after spawning in S. paramamosain and can maintain the status of the first ovarian maturation; however, the hepatopancreas gradually degenerate during the SVP.

The mud crab, Scylla paramamosain, has abundant nutrients in the ovary, where numerous lipids accumulate during ovarian maturation. However, the mechanism behind the accumulation of lipids in the ovary of mud crab during ovarian maturation is largely unknown. This study conducted a comparative transcriptome analysis of the ovaries of mud crabs at various stages of ovarian maturation. A total of 63.69 Gb of clean data was obtained, with a Q30 of 93.34%, and 81,893 unigenes were identified, including 10,996 differentially expressed genes (DEGs). After KEGG enrichment of these DEGs, MAPK signaling pathway was significantly enriched during vitellogenesis. Moreover, the expression levels of genes involved in carbohydrate, amino acid, and lipid metabolism were found to be higher during vitellogenesis. The two genes (Sp-Eip75B and Sp-Eip78C) that are homologous to the vertebrate gene PPARγ in the PPAR signaling pathway, were identified. Additionally, genes in MAPK signaling pathway might regulate lipid metabolism through PPAR signaling pathway based on Protein-Protein Interaction (PPI) network. These findings suggest that MAPK signaling pathway plays a critical role in lipid metabolism in the ovary during vitellogenesis, which provides new insights into the mechanism of lipid accumulation during ovarian maturation in mud crabs.

Although the pathway and transcription factor regulation of anthocyanin biosynthesis in tea plants [Camellia sinensis (L.) O. Ktze] are known, post-transcriptional regulation mechanisms involved in anthocyanin accumulation have not been comprehensively studied. We obtained the full-length transcriptome of a purple cultivar (‘Zijuan’) and a normal green cultivar (‘Yunkang 10#) of C. sinensis var. asssamica (Masters) showing different accumulation of anthocyanins and catechins through PacBio isoform sequencing (Iso-Seq). In total, 577,557 mapped full-length cDNAs were obtained, and 2,600 average-length gene isoforms were identified in both cultivars. After gene annotations and pathway predictions, we found that 98 key genes in anthocyanin biosynthesis pathways could have undergone alternative splicing (AS) events, and identified a total of 238 isoforms involved in anthocyanin biosynthesis. We verified expression of the C4H, CHS, FLS, CCOM, F3′5’H, LAR, PAL, CCR, CYP73A13, UDP75L12, UDP78A15/UFGT, UDP94P1, GL3, MYB113, ANR, ANS, F3H, 4CL1, CYP98A3/C3H, CHI, DFR genes and their AS transcripts using qRT-PCR. Correlation analysis of anthocyanin biosynthesis and gene expression results revealed that C4H1, FLS1, PAL2, CCR2, UDP75L122 and MYB113-1 are crucial AS transcripts for regulating anthocyanin biosynthesis in C. sinensis var. assamica. Our results reveal post-transcriptional regulation of anthocyanin biosynthesis in tea plants, and provide more new insights into the regulation of secondary metabolism.

Background: Lower-grade gliomas (LGGs) are a heterogeneous set of gliomas. One of the primary sources of glioma heterogeneity is genomic instability, a novel characteristic of cancer. It has been reported that long noncoding RNAs (lncRNAs) play an essential role in regulating genomic stability. However, the potential relationship between genomic instability and lncRNA in LGGs and its prognostic value is unclear.Methods: In this study, the LGG samples from The Cancer Genome Atlas (TCGA) were divided into two clusters by integrating the lncRNA expression profile and somatic mutation data using hierarchical clustering. Then, with the differentially expressed lncRNAs between these two clusters, we identified genomic instability-related lncRNAs (GInLncRNAs) in the LGG samples and analyzed their potential function and pathway by co-expression network. Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were conducted to establish a GInLncRNA prognostic signature (GInLncSig), which was assessed by internal and external verification, correlation analysis with somatic mutation, independent prognostic analysis, clinical stratification analysis, and model comparisons. We also established a nomogram to predict the prognosis more accurately. Finally, we performed multi-omics-based analyses to explore the relationship between risk scores and multi-omics data, including immune characteristics, N6-methyladenosine (m6A), stemness index, drug sensitivity, and gene set enrichment analysis (GSEA).Results: We identified 52 GInLncRNAs and screened five from them to construct the GInLncSig model (CRNDE, AC025171.5, AL390755.1, AL049749.1, and TGFB2-AS1), which could independently and accurately predict the outcome of patients with LGG. The GInLncSig model was significantly associated with somatic mutation and outperformed other published signatures. GSEA revealed that metabolic pathways, immune pathways, and cancer pathways were enriched in the high-risk group. Multi-omics-based analyses revealed that T-cell functions, m6A statuses, and stemness characteristics were significantly disparate between two risk subgroups, and immune checkpoints such as PD-L1, PDCD1LG2, and HAVCR2 were significantly highly expressed in the high-risk group. The expression of GInLncSig prognostic genes dramatically correlated with the sensitivity of tumor cells to chemotherapy drugs.Conclusion: A novel signature composed of five GInLncRNAs can be utilized to predict prognosis and impact the immune status, m6A status, and stemness characteristics in LGG. Furthermore, these lncRNAs may be potential and alternative therapeutic targets.

Spodoptera frugiperda is the world’s major agricultural pest and has the distinctive features of high fecundity, strong migratory capacity, and high resistance to most insecticides. At present, the control of S. frugiperda in China relies mainly on the spraying of chemical insecticides. MicroRNAs (miRNAs) are a class of small, single-stranded, non-coding RNAs and play crucial regulatory roles in various physiological processes, including the insecticide resistance in insects. However, little is known about the regulatory roles of miRNAs on the resistance of S. frugiperda to insecticides. In the present research, the miRNAs that were differentially expressed after cyantraniliprole, spinetoram, and emamectin benzoate treatment were analyzed by RNA-Seq. A total of 504 miRNAs were systematically identified from S. frugiperda, and 24, 22, and 31 miRNAs were differentially expressed after treatments of cyantraniliprole, spinetoram, and emamectin benzoate. GO and KEGG enrichment analyses were used to predict the function of differentially expressed target genes of miRNAs. Importantly, ten miRNAs were significantly differentially expressed among the treatments of three insecticides. miR-278-5p, miR-13b-3p, miR-10485-5p, and miR-10483-5p were significantly downregulated among the treatments of three insecticides by RT-qPCR. Furthermore, the overexpression of miR-278-5p, miR-13b-3p, miR-10485-5p, and miR-10483-5p significantly increased the mortality of S. frugiperda to cyantraniliprole and emamectin benzoate. The mortality was significantly increased with spinetoram treatment after the overexpression of miR-13b-3p, miR-10485-5p, and miR-10483-5p. These results suggest that miRNAs, which are differentially expressed in response to insecticides, may play a key regulatory role in the insecticide tolerance in S. frugiperda.

IntroductionGlioma is the most common primary cancer of the central nervous system with dismal prognosis. Long noncoding RNAs (lncRNAs) have been discovered to play key roles in tumorigenesis in various cancers, including glioma. Because of the relevance between immune infiltrating and clinical outcome of glioma, identifying immune-related lncRNAs is urgent for better personalized management.Materials and methodsSingle-sample gene set enrichment analysis (ssGSEA) was applied to estimate immune infiltration, and glioma samples were divided into high immune cell infiltration group and low immune cell infiltration group. After screening differentially expressed lncRNAs in two immune groups, least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed to construct an immune-related prognostic signature. Additionally, we explored the correlation between immune infiltration and the prognostic signature.ResultsA total of 653 samples were appropriate for further analyses, and 10 lncRNAs were identified as immune-related lncRNAs in glioma. After univariate Cox regression and LASSO Cox regression analysis, six lncRNAs were identified to construct a prognostic signature for glioma, which could be taken as independent prognostic factors in both univariate and multivariate Cox regression analyses. Moreover, risk score was significantly correlated with all the 29 immune-related checkpoint expression (p < 0.05) in ssGSEA except neutrophils (p = 0.43).ConclusionThe study constructed an immune-related prognostic signature for glioma, which contributed to improve clinical outcome prediction and guide immunotherapy.

In this study, the complete mitochondrial genome of Ariosoma meeki was sequenced, assembled and annotated. The circular genome is 16,154 bp in length with nucleotide composition is 28.42% A, 26.53% T, 19.65% G, and 25.40% C and contains 13 protein-coding genes (PCGs), 21 transfer RNA genes (tRNAs), 2 ribosomal RNA unit genes and a large non-coding region (putative control region). To further explore the evolution relationship of the Anguilliformes, we constructed the phylogenetic tree and found that the A. meeki had closer relationship with Ariosoma shiroanago. This study provided the valuable evidence on phylogenetic relationship of the A. meeki at the molecular level and essential resource for further study the molecular phylogenetic, biogeography and adaptive evolution of this lineage.

Abstract Background Toll-like receptor 4 (TLR4) expression is increased in activated monocytes, which play a critical role in the pathogenesis of coronary artery disease (CAD). However, the mechanism remains unclear. Regulatory factor X1 (RFX1) is a critical transcription factor regulating epigenetic modifications. In this study, we investigated whether RFX1 and epigenetic modifications mediated by RFX1 contributed to the overexpression of TLR4 in activated monocytes. Results Compared with those of the controls, the mRNA and protein expression of RFX1 were downregulated and the mRNA expression of TLR4 was upregulated in CD14+ monocytes obtained from CAD patients and CD14+ monocytes obtained from healthy controls treated with low-density lipoprotein (LDL). The mRNA expression of RFX1 was negatively correlated with the mRNA expression of TLR4 in CD14+ monocytes. RFX1 knockdown led to the overexpression of TLR4 and the activation of CD14+ monocytes. In contrast, the overexpression of RFX1 inhibited TLR4 expression and the activation of CD14+ monocytes stimulated with LDL. Moreover, TLR4 was identified as a target gene of RFX1. The results indicated that RFX1 downregulation contributed to the decreased DNA methylation and histone H3 lysine 9 trimethylation and the increased H3 and H4 acetylation in the TLR4 promoter via the lack of recruitments of DNA methyltransferase 1 (DNMT1), histone deacetylase 1 (HDAC1), and histone-lysine N-methyltransferase SUV39H1 (SUV39H1), which were observed in CD14+ monocytes of CAD patients. Conclusions Our results show that RFX1 expression deficiency leads to the overexpression of TLR4 and the activation of CD14+ monocytes in CAD patients by regulating DNA methylation and histone modifications, which highlights the vital role of RFX1 in the pathogenesis of CAD.

Glioma is the common histological subtype of malignancy in the central nervous system, with high morbidity and mortality. Glioma cancer stem cells (CSCs) play essential roles in tumor recurrence and treatment resistance. Thus, exploring the stem cell-related genes and subtypes in glioma is important. In this study, we collected the RNA-sequencing (RNA-seq) data and clinical information of glioma patients from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. With the differentially expressed genes (DEGs) and weighted gene correlation network analysis (WGCNA), we identified 86 mRNA expression-based stemness index (mRNAsi)-related genes in 583 samples from TCGA RNA-seq dataset. Furthermore, these samples from TCGA database could be divided into two significantly different subtypes with different prognoses based on the mRNAsi corresponding gene, which could also be validated in the CGGA database. The clinical characteristics and immune cell infiltrate distribution of the two stemness subtypes are different. Then, functional enrichment analyses were performed to identify the different gene ontology (GO) terms and pathways in the two different subtypes. Moreover, we constructed a stemness subtype-related risk score model and nomogram to predict the prognosis of glioma patients. Finally, we selected one gene (ETV2) from the risk score model for experimental validation. The results showed that ETV2 can contribute to the invasion, migration, and epithelial-mesenchymal transition (EMT) process of glioma. In conclusion, we identified two distinct molecular subtypes and potential therapeutic targets of glioma, which could provide new insights for the development of precision diagnosis and prognostic prediction for glioma patients.

Monocyte chemoattractant protein 1 (MCP1) affects the chemotaxis of monocytes and is a key chemokine closely related to the development of atherosclerosis (AS). Compared with healthy controls, coronary heart disease (CAD) patients show significantly upregulated plasma concentrations and mRNA expression of MCP1 in CD14+ monocytes. However, the specific regulatory mechanism of MCP1 overexpression in AS is still unclear. Our previous research indicated that there was no significant difference in the H3K4 and H3K27 tri-methylation of the MCP1 promoter in CD14+ monocytes from CAD versus non-CAD patients, but the H3 and H4 acetylation of the MCP1 promoter was increased in CD14+ monocytes from CAD patients. We further found that the H3K9 tri-methylation of the MCP1 promoter in CD14+ monocytes from CAD patients was decreased, but the DNA methylation levels did not differ markedly from those in non-CAD patients. Our previous work showed that the level of regulatory factor X1 (RFX1) was markedly reduced in CD14+ monocytes from CAD patients and played an important role in the progression of AS by regulating epigenetic modification. In this study, we investigated whether RFX1 and epigenetic modifications mediated by RFX1 contribute to the overexpression of MCP1 in activated monocytes in CAD patients. We found that the enrichment of RFX1, histone deacetylase 1 (HDAC1), and suppressor of variegation 3–9 homolog 1 (SUV39H1) in the MCP1 gene promoter region were decreased in CD14+ monocytes from CAD patients and in healthy CD14+ monocytes treated with low-density lipoprotein (LDL). Chromatin immunoprecipitation (ChIP) assays identified MCP1 as a target gene of RFX1. Overexpression of RFX1 increased the recruitments of HDAC1 and SUV39H1 and inhibited the expression of MCP1 in CD14+ monocytes. In contrast, knockdown of RFX1 in CD14+ monocytes reduced the recruitments of HDAC1 and SUV39H1 in the MCP1 promoter region, thereby facilitating H3 and H4 acetylation and H3K9 tri-methylation in this region. In conclusion, our results indicated that RFX1 expression deficiency in CD14+ monocytes from CAD patients contributed to MCP1 overexpression via a deficiency of recruitments of HDAC1 and SUV39H1 in the MCP1 promoter, which highlighted the vital role of RFX1 in the pathogenesis of CAD.

Abstract Background Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterized by lymphocytic infiltration and overproduction of autoantibodies, leading to significant morbidity and mortality. However, the pathogenesis of this disorder has not yet been completely elucidated. It has been reported that CD70, a B cell costimulatory molecule encoded by the gene TNFSF7 (tumor necrosis factor ligand superfamily member 7), is overexpressed in CD4+ T cells from patients with SLE due to the demethylation of its promoter. We aimed to investigate the expression patterns of MBD4 (methyl-CpG binding domain protein 4) in CD4+ T cells and its contribution to the pathogenesis of SLE by increasing CD70 expression through epigenetic regulation. Results Our results showed that the expression of MBD4 was significantly decreased in CD4+ T cells from SLE patients. We verified that transfection of MBD4 siRNA into healthy CD4+ T cells upregulated expression of CD70 and decreased the methylation level of the CD70 promoter. Overexpression of MBD4 inhibited CD70 expression and enhanced the DNA methylation level of CD70 in CD4+ T cells of SLE patients. Conclusion Our results indicated that downregulation of MBD4 contributed to overexpression and hypomethylation of the CD70 gene in SLE CD4+ T cells. This modulation of MBD4 may provide a novel therapeutic approach for SLE.

The complete mitochondrial genome DNA sequence of Lepidotrigla kanagashira was 16,504 bp in length. It consists of 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes and one control region. Among 22 tRNA genes, 8 tRNAs were encoded on the L-strand. The overall base composition of the genome is 26.65% for A, 25.42% for T, 30.89% for C and17.04% for G. The phylogenetic tree suggested that L. kanagashira was genetically closest to L. microptera and Chelidonichthys kumu among 13 related species. This study could provide some valuable information for further studies on L. kanagashira.

Motivation: The number of ion channels is increasing rapidly. As many of them are associated with diseases, they are the targets of more than 700 drugs. The discovery of new ion channels is facilitated by computational methods that predict ion channels and their types from protein sequences.Methods: We used the SVMProt and the k-skip-n-gram methods to extract the feature vectors of ion channels, and obtained 188- and 400-dimensional features, respectively. The 188- and 400-dimensional features were combined to obtain 588-dimensional features. We then employed the maximum-relevance-maximum-distance method to reduce the dimensions of the 588-dimensional features. Finally, the support vector machine and random forest methods were used to build the prediction models to evaluate the classification effect.Results: Different methods were employed to extract various feature vectors, and after effective dimensionality reduction, different classifiers were used to classify the ion channels. We extracted the ion channel data from the Universal Protein Resource (UniProt, http://www.uniprot.org/) and Ligand-Gated Ion Channel databases (http://www.ebi.ac.uk/compneur-srv/LGICdb/LGICdb.php), and then verified the performance of the classifiers after screening. The findings of this study could inform the research and development of drugs.

Abstract Post‐translational modifications in intestinal epithelial cells (IECs) allow for precise control in intestinal homeostasis, the breakdown of which may precipitate the pathological damage and inflammation in inflammatory bowel disease. The O‐linked β‐N‐acetylglucosamine (O‐GlcNAc) modification on intracellular proteins controls diverse biological processes; however, its roles in intestinal homeostasis are still largely unexplored. Here, we found that levels of protein O‐GlcNAcylation and the expression of O‐GlcNAc transferase (OGT), the enzyme adding the O‐GlcNAc moiety, were reduced in IECs in human IBD patients. Deletion of OGT specifically in IECs resulted in disrupted epithelial barrier, microbial dysbiosis, Paneth cell dysfunction, and intestinal inflammation in mice. Using fecal microbiota transplantation in mice, we demonstrated that microbial dysbiosis although was insufficient to induce spontaneous inflammation but exacerbated chemical‐induced colitis. Paneth cell‐specific deletion of OGT led to Paneth cell dysfunction, which might predispose mice to chemical‐induced colitis. On the other hand, the augmentation of O‐GlcNAc signaling by inhibiting O‐GlcNAcase, the enzyme removing O‐GlcNAcylation, alleviated chemical‐induced colitis. Our data reveal that protein O‐GlcNAcylation in IECs controls key regulatory mechanisms to maintain mucosal homeostasis.

Gastrointestinal stromal tumor (GIST) is a refractory disease in need of novel efficacious therapy. The aim of our study was to evaluate the effectiveness of tumor-targeting Salmonella typhimurium A1-R (S. typhimurium A1-R) using on a patient derived orthotopic xenograft (PDOX) model of imatinib-resistant GIST. The GIST was obtained from a patient with regional recurrence, and implanted in the anterior gastric wall of nude mice. The GIST PDOX mice were randomized into 3 groups of 6 mice each when the tumor volume reached 60 mm3: G1, control group; G2, imatinib group (oral administration [p.o.], daily, for 3 weeks); G3, S. typhimurium A1-R group (intravenous [i.v.] injection, weekly, for 3 weeks). All mice from each group were sacrificed on day 22. Relative tumor volume was estimated by laparotomy on day 0 and day 22. Body weight of the mouse was evaluated 2 times per week. We found that S. typhimurium A1-R significantly reduced tumor growth in contrast to the untreated group (P = 0.001). In addition, we found that S. typhimurium A1-R was more effective compared to imatinib (P = 0.013). Furthermore, Imatinib was not significantly effective compared to the control group (P = 0.462). These results indicate that S. typhimurium A1-R may be new effective therapy for imatinib-resistant GIST and therefore a good candidate for clinical development of this disease.

The complete mitochondrial genome DNA sequence of Istigobius campbelli was 16,527 bp in length. It consists of 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and 1 control region. 28 of the 37 genes were encoded on the heavy strand, and 9 of them were encoded on the light strand. The overall base composition of the genome is 27.84% A, 25.81% T, 29.68% C, and 16.67% G. The phylogenetic tree suggested I. campbelli was genetically closest to Acentrogobius pflaumii and Oxyurichthys formosanus. This study could provide valuable information for further studies on I. campbelli.

In this study, the complete mitochondrial genome of Dysomma anguillare was obtained, which was 16,898 bp in length. It consists of 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and a non-coding control region. The overall base composition of the genome is 33.19% for A, 22.9% for T, 28.1% for C, and 15.79% for G. In 13 protein-coding genes, two types of initiation codon (GTG, ATG) and five types of stop codons (AGG,TAA,TAG,TA, and T) were identified. The phylogenetic tree, which is based on complete mtDNA sequences, suggested that D. anguillare was closest to some species of Synaphobranchidae. This study could provide some basic information for further studies on population structure and molecular evolution of D. anguillare.

Gymnodraco acuticepsis is an Antarctic fish living in the Southern Ocean. Until now, studies on G. acuticeps are still limited. As an Antarctic fish, obtaining and characterization of the mitochondrial genome of G. acuticeps will be important for elucidation of the mechanism of cold-adapting evolution in mitochondrion. In this study, we first isolated and characterized the mitochondrial genome sequence of G. acuticeps with 15,987 bp in length. It contained of 34 genes (12 protein-coding genes, 20 transfer RNA genes, 2 ribosomal RNA genes) and a partial putative control region. Gene organization and nucleotide composition of obtained mito-genome were similar to those of other Antarctic fish. Twenty-eight genes were encoded by heavy strand, while six genes were encoded by light strand. Further, the phylogenetic tree, which based on 12 protein-coding genes, revealed that the G. acuticeps was genetically closest to species Parachaenichthys charcoti among 18 species. We hope this work would be helpful for the population genetics and molecular evolution studies.

Antarctic krill Euphausia superba is a very important species in Antarctic ecosystem. The mitochondrial genome of E. superba was completed with 16,591 bp in length, gene arrangement and order was the same as previous studies. The overall A + T content is 68.91% and the control region A + T content is 78.17%. Alignment with other two partial mitochondrial genome revealed that ND2 region possessed many unusual variation sites. The phylogenetic tree showed that E. superba clustered with other two species of Euphausiacea. This study filled in the gap of the krill mitogenome and suggested putative markers for population study.