
Ferroptosis is a new type of iron-dependent programmed cell death, which is different from apoptosis, necrosis and pyrodeath. Its main characteristics are iron accumulation and lipid peroxidation. Studies have shown that ferroptosis plays an important role in kidney related diseases such as acute kidney injury and renal cancer, whereas its exact mechanism has not been fully revealed. With the development of the research on the mechanism of iron death, ferroptosis shows a good application prospect in the treatment of renal diseases. In this paper, the mechanism of ferroptosis and the research progress in renal related diseases are reviewed, in order to provide new ideas and research directions for the treatment of renal related diseases.
The COVID-19 pandemic caused by SARS-CoV-2 is still prevalent around the world. Vaccine development, promotion, usage are key means to prevent COVID-19. Nuclearcapsid protein (NP), as the main structural protein of SARS-CoV-2, is a potential candidate target for vaccine development. Flagellin B (FlaB) has been used as an immune adjuvant to enhance the immunogenicity of antigens. In this research, we analyzed the immunogenicity of NP and a NP-FlaB fusion protein. Firstly, the NP, NP-FlaB fusion protein were expressed and purified by the E. coli system; then the BALB/c mice were immunized with the antigens by subcutaneous or intranasal route; the NP-specific serum IgG, mucosal IgA and cytokine secreting T cell responses were analyzed. The results showed that: one-time subcutaneous immunization of NP or NP-FlaB fusion protein was sufficient to elicit robust anti-NP serum IgG antibody response and IL-4 secreting T cell response, and no significant differences were observed between NP and NP-FlaB fusion protein. However, when inoculated by the intranasal route, NP-FlaB fusion protein introduced significantly higher NP-specific serum IgG titer, as well as the higher mucosal IgA titer at the resident of lung. The overall results showed that, SARS-CoV-2 NP and NP-FlaB fusion protein are highly immunogenicity, NP-FlaB fusion protein can induce mucosal immune response, both of them are effective candidates for SARS-CoV-2 vaccine. In summary, our research on the immunogenicity of NP and NP-FlaB of SARS-CoV-2 provided a new idea and reference for the subsequent development of SARS-CoV-2 vaccine based on NP.
In order to further screen and identify SARS-CoV-2 accurately and to look for mutation sites which may be related to the ability of transmission and the intensity of symptoms, we have conducted metatranscriptome sequencing and hybrid capture-based sequencing for 12 imported cases confirmed COVID-19 back from Europe to Zhejiang province and 7 domestic SARS-CoV-2 infected cases from China. The result indicated that the capture sequencing samples have accurate mutation detection results, whereas the required data is only~1/10 or less of metatranscriptomic sequencing, which is a more suitable detection method for low viral load samples. Mutation analysis with reference genome (EPI~~ISL~~402119) showed that most of the domestic virus samples are ORF8:L84S mutation, foreign virus samples are mainly S:D614G mutation, and the rest of the samples were found 2 mutations in the virus gene ORF1a, namely ORF1a:C409S and ORF1a:P1207H. Variation analysis indicated that there are different mutation groups of the SARS-CoV-2 virus genomes in patients with SARS-CoV-2 between China and Italy. The detection of different single nucleotide variations (SNVs) between samples indicated the variation polymorphism of SARS-CoV-2 genomes. Analysis of intra-individual single nucleotide variations (iSNVs) of virus sequencing data in the same host indicated that the iSNVs in gene region of F06 and F11 were unexpectedly the same as the mutation of the other 5 samples from the same Italian restaurant, which indicated they might had co-infection in the same patient.
Green tide is a common marine ecological disaster in offshore China. In order to use the UAV RGB optical camera to accurately monitor the green tide and establish a fast extraction index for green algae in high-resolution RGB optical images. A new index is proposed to enhance the signal of floating green algae. A virtual baseline is formed in the green and red bands, and the line-height of the blue band signal under this virtual baseline is the red-green band virtual baseline floating green algae index (RG-FAH). In addition, representative UAV images under different conditions are used to compare with other vegetation indices for verification. The experimental results show that the accuracy and kappa of RG-FAH under different conditions are all above 0.91. Under normal and overexposure conditions and the extraction of large patches of algae, RG-FAH appears to be comparable to GB, yet it is more beneficial than GB and other indices in terms of sun glitter tolerance and small patches of algae extraction. The RG-FAH index proposed in this study has potential application value in monitoring green algae and similar floating green plants in seawater. It can also provide effective information support for the monitoring and management of green tide.
Mycobacterium tuberculosis, the pathogen of tuberculosis, is one of the deadliest pathogens of infectious diseases, however the epidemic situation of COVID-19 in 2019 dealt a heavy blow to the prevention and treatment of tuberculosis. Therefore, the in-depth study of Mycobacterium tuberculosis is of great significance. The study of genomics shows that DNA-3-methyladenine glycosylase I TagA from Mycobacterium tuberculosis (MtbTagA) recognizes and removes damaged alkylated bases in order to maintain normal replication, transcription and translation of the genome, whereas the type of binding substrate, catalytic mechanism and structural basis are not clear. In this study, MtbTagA was heterologous expressed in E. coli, and the high purity protein was obtained by nickel medium affinity chromatography, anion exchange chromatography and gel filtration chromatography. Dynamic light scattering (DLS) experiments showed that MtbTagA protein was distributed as a monomer in solution and could bind to substrate 3-methyladenine (3MA) and hypoxanthine (Hx) and change its aggregation state. The flake crystals were selected and optimized by further crystallization, and the diffraction data with a resolution of 7?? were obtained. It provides a reference for further study on the biochemical properties and structure of DNA glycosylase protein.
The heart development genes of Drosophila melanogaster are highly conserved with human heart development genes. Lbe (Ladybird early) is one of the important genes involved in Drosophila heart development. In order to further understand the regulatory role of Lbe gene in heart development, the anti-Lbe antibody is prepared with DNA immunization technique. The Lbe coding sequence was amplified with PCR, and then it was homologously recombined with the eukaryotic expression vector pCAGGS-P7. This homologous recombinant vector was used as antigen to immunize four weeks old mice to obtain the serum containing anti-Lbe polyclonal antibody. Western blot and embryo antibody staining results showed that the specificity of the antibody was good. The antibody provides a foundation for the subsequent study of function of Lbe.
The aim of this study was to determine the frequencies and parameters of 20 STR loci among Kazakh, Hui and Han population in Shihezi area of Xinjiang. The 20 STR loci of unrelated individuals of three population in Shihezi were amplified by DNATyperTM21 Kit, and the amplification products were analyzed through 3500xL genetic analyzer. Genetic polymorphism data and genetic distance were analyzed by PowerStats v12, Arlequin v3.5, Phylip-3.695 software. 231 alleles were identified in Kazakh population with their F ranging from 0.000 8~0.500 8. Heterozygosity (H) ranged among 0.669~0.923, discriminant power (DP) ranged among 0.817~0.988, polymorphism information content (PIC) ranged among 0.60~0.92, and paternity exclusion (PE) ranged among 0.380~0.843, comulative probability of exclusion presented 0.999 999 999 in triplet setting (CEPtri) and 0.999 998 212 in duo sttuations (CEPduo), total probability of discrimination power (TDP) was within 1-7.60×10–26; 237 alleles were identified in Hui population with their F ranging from 0.000 8 ~0.533 4. H ranged among 0.833~0.928, DP ranged among 0.949~0.986, PIC ranged among 0.81~0.91, and PE ranged among 0.661~0.853, comulative probability of exclusion presented 0.999?999?996 in CEPtri and 0.999?996 725 in CEPduo, TDP was within 1-4.77×10–25; 253 alleles were identified in Han population with their F ranging from 0.000?8~0.541?0. H ranged among 0.829~0.943, DP ranged among 0.958~0.986, PIC ranged among 0.83~0.91, and PE ranged among 0.655~0.884, comulative probability of exclusion presented 0.999?999?996 in CEPtri and 0.999?995?459 in CEPduo, TDP was within 1-1.15×10–24. The genetic distance was calculated by Phylip-3.695 softwarit, and was relatively far apart between Kazakh and Hui, Han, whereas relatively close between Han and Hui. The results of this work provided reference data for human population genetics and forensic DNA research in this area.
The role of human glycolipid transfer protein (GLTP) in initiation and progression of tumor and its epigenetic regulation mechanisms were analyzed by bioinformatics methods. The expression and survival analysis results of human GLTP in pancreatic adenocarcinoma (PAAD) tissues was significantly higher than that in adjacent normal tissues by using online bioinformatics analysis tools such as UCSC Genome Browser, EMBOSS and GEPIA. These results suggest that GLTP may be involved in the initiation and progression of PAAD. The analysis of GLTP expression level and pathological stage of PAAD patients showed that there was no significant difference in GLTP expression level among different pathological stages of PAAD patients. The results of methylation analysis showed that the methylation level of human GLTP was significantly correlated with the expression level of GLTP in PAAD cells. The results of histone modification analysis indicate that histone H3K4Me1 and H3K27Ac may affect initiation and progression of tumor by up-regulating the expression of human GLTP. The results of competing endogenous RNAs (ceRNA) regulation analysis show that human GLTP has potential effects on a variety of microRNAs (miRNAs), and these miRNAs are strongly associated with many tumors and signaling pathways. The results of this study provide a reference for the further study of the function and epigenetic regulation mechanisms of human GLTP.
Colorectal cancer is one of the most common malignant tumors worldwide. At present, the molecular mechanism of colorectal cancer is still under continuous exploration. In order to determine the carcinogenic effect and progress of related candidate genes in colorectal cancer. Three data sets were selected from the gene expression database (GEO) [GSE21510 (148 samples), GSE32323 (44 samples), GSE15781 (42 samples)], and analyzed the expression of differential genes and functional enrichment. By establishing a protein interaction network, using STRING and Cytoscape to analyze molecules. A total of 472 differential genes were selected, including 212 up-regulated genes and 260 down-regulated genes. The rich functions of differential genes and their pathways mainly include regulation of cell proliferation, cell activity, ion transmission, decomposition of lipids, multicellular organisms, cytokine biosynthesis, monosaccharide metabolism, recognition of receptor signaling pathways, and carbonate dehydration enzyme activity, sodium reabsorption, peroxisome proliferator activated-receptor signaling pathway, and starch and sucrose metabolism. During the process of identifying and analyzing 15 core genes, it was found that these genes were mainly enriched in receptor protein signaling pathway, cell surface receptor signal transduction, and cytokine activity, growth factor activity, and chemokine signaling pathway. Survival analysis showed that AGT, CXCL2 may be involved in carcinogenesis, promote cancer metastasis, and affect prognosis. Through the screening and identification of 472 differential genes and 15 core genes, the tumor suppressor gene AGT and the tumor-promoting gene CXCL2 may be regarded as biomarkers of colorectal cancer, providing new information for the diagnosis, treatment and research of colorectal cancer molecular target.
To investigate the methylation of NMUR1 (neuromedin U receptor 1) in breast invasive cancer (BRCA) and its prognostic role in prognosis, the UALCAN database was used to analyze the expression level of NMUR1 in TCGA (the cancer genome atlas)-BRCA tissues, and The Human Protein Atlas database was used for verification. SurvivalMeth database was used to analyze the methylation levels of NMUR1 in BRCA, and COX regression analysis and Kaplan-Meier survival analysis were conducted to study the correlation between the methylation levels of NMUR1 and the prognosis of BRCA patients. In the UALCAN database, 1?097 TCGA breast cancer tissue and 114 normal breast tissue were included, and NMUR1 expression was significantly down-regulated in breast tissue compared with normal breast tissue (P<0.001). The methylation analysis showed that NMUR1 had significant differences in the methylation levels of cg00143376, cg01649597, cg02204630, cg10042319, cg16297948, cg17207690, cg18250832, cg18877969, cg19077400, cg21424120 and cg26913833 in BRCA tissues (P<0.001). Kaplan-Meier survival analysis showed that the survival rate of NMUR1 patients in the high-risk CpG island methylation group (n=320) in BRCA tissues was significantly lower than that in the low-risk group (n=461) [HR=2.1403, 95%CI (1.305 4, 3.509 1), P=0.001]. Compared with the low-risk group, the CpG island methylation level was higher in the high-risk group at cg18877969 (P=0.015), cg16297948 (P=0.028), cg19077400 (P=0.011), and cg26913833 (P=0.035). NMUR1 is hypermethylated in BRCA tissues, and CpG island methylation of NMUR1 is related to the prognosis of BRCA patients, that providing evidence for NMUR1 as a new target for BRCA prognosis and/or treatment.
In order to study the biological control methods of fish furunculosis, actinomycete I6 strain with strong antagonistic activity was screened from soil by using the fish furunculosis pathoge Aeromonas salmonicida as indicator strain. 16S rRNA analysis indicates that it is a Streptomyces sp. strain. The secondary metabolites produced by I6 exhibit strong antibacterial activity to A. salmonicida in vitro, and no obvious adverse effect on fish was observed. This result provides a reference for the treatment and prevention of A. salmonicida. In order to enhance the yield of the antibacterial active substance of I6, the fermentation conditions of the I6 strain were optimized. The results showed that the optimal fermentation medium is determined to be AM3-1 with initial pH of 7~8, and the optimal cultivation time is 5 days. The optimum bacterial age for seed liquid is 36 h. All these results shows that I6 has a significant inhibitory effect on the growth of fish furunculosis pathogen A. salmonicida, and has potential development and application value in fishery biocontrol.
To explore the genetic basis of a patient with hypergonadotropic amenorrhea and normal number of antral follicles, and provide a basis for genetic counseling and direction for reproduction, the proband was subjected to whole exome sequencing and her sister, brother and parents performed sanger sequencing on FSHR gene mutation loci. We applied the bioinformatics analysis according to clinical characterization of the patient. The proband was found to harbor compound heterozygous variants of the FSHR gene in exon 5 c.392G>A (p.Gly131Asp) and exon 4 c.301A>G (p.Lys104Glu), which were respectively inherited from her mother and father. The sister and brother were found to have the same FSHR gene complex heterozygous variation as the patient. Pedigree and bioinformatic analysis suggested that both mutations were likely pathogenic according to the ACMG guidelines. The clinical data and literature review suggested that the patient was affected with resistant ovary syndrome rather than premature ovarian failure. In this study, FSHR gene compound heterozygous variation was identified as a possible genetic cause of primary amenorrhea and infertility in the patient and her sister. Infertility is a kind of disease with very high genetic heterogeneity, and it is difficult to distinguish the diseases by routine detection in clinical practice. Genetic detection is of great significance for the detection of such diseases. At the same time, few pathogenic variants of FSHR gene have been reported in Chinese population. The detection of two new mutation sites of FSHR gene in the family of ovarian resistance syndrome in this paper enriches the mutation spectrum of FSHR gene, which has important reference significance for the diagnosis of this disease in the future.