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it was to explore the mechanism of Japanese encephalitis virus (JEV) and micro ribonucleic acid (miRNA) under high-throughput sequencing. 20 experimental mice, with good growth status and no disease infection, were selected. The cells used in the experiment included mouse microglial cell line (BV2), mouse neuroblastoma cell line (NA), and mouse brain endothelial cell line (bEnd.3). JEV titration was performed with JEV-infected cells, ribonucleic acid (RNA) in the cells was extracted, and finally the miRNA high-throughput sequencing data was analyzed. Agarose gel electrophoresis showed that the 28S and 18S electrophoresis bands were bright. Among the miRNAs detected in mouse brain tissues, 2986 were down-regulated and 1251 were up-regulated. Among miRNAs detected in NA cells, 4238 the decreasing expression and 2356 were expressed increasingly. In reducing miRNA expression, 1 multiplicity of infection (MOI) of P3 strain infection was more significant than 0.1 MOI. 10 miRNAs with significantly decreasing expression were miR-466d-3p, miR-381-3p, miR-540-3p, miR-466a-3p, miR-467a-3p, miR-574-5p, miR-199a-5p, miR-467a-5p, miR-674-5p, and miR-376b-3p. These were all obviously down-regulated in JEV-infected BV2, NA, and bEnd.3 neurons. High-throughput sequencing of JEV-infected mouse brain tissues and mouse neuronal cells found that JEV infection led to down-regulation of overall miRNA expression in host cells.
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Vírus da Encefalite Japonesa (Espécie) , Encefalite Japonesa , MicroRNAs , Animais , Camundongos , Vírus da Encefalite Japonesa (Espécie)/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Encefalite Japonesa/genética , Linhagem Celular , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
BACKGROUND: Myelodysplastic syndromes (MDS) are a class of myeloid neoplasms featuring inefficient maturation and differentiation of hematopoietic cells, blood cytopenia, and a high risk of leukemia onset. The diagnosis of MDS remains a challenging task owing to its complexity, heterogeneity, and the lack of specific characteristics. METHODS: To look for an easy and inexpensive diagnostic method for MDS, we tried to establish an FCM scoring systems (FCSS) with a combination of antibodies for diagnosis and prognostic stratification of MDS. This FCSS adopted four parameters; i.e., the frequency of myeloblasts in nucleated cells, the ratio between pro-B cells and CD117+ cells, the ratio of CD45 mean fluorescence intensity between lymphocytes and myeloblasts, and the ratio of SSC peak values between mature granulocytes and lymphocytes. RESULTS: We tested the correlation between the total FCSS score with conventional IPSS-R. Additionally, the correlation between the score of each FCSS parameter and IPSS-R was also evaluated. We found that total FCSS score had a positive correlation with IPSS-R, while FCSS parameter 1 and 4 were also correlated with IPSS-R. Furthermore, this FCSS had a sound sensitivity and specificity in the diagnosis of MDS. CONCLUSIONS: The FCSS represents a convenient and affordable approach for the diagnosis and prognostic stratification of MDS.
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Leucemia , Síndromes Mielodisplásicas , Compostos Férricos , Citometria de Fluxo/métodos , Humanos , Contagem de Leucócitos , Maltose/análogos & derivados , Síndromes Mielodisplásicas/diagnóstico , PrognósticoRESUMO
BACKGROUND: Human apolipoprotein E (APOE) polymorphisms are attributable to the presence of three common alleles, namely, ε2, ε3, and ε4, which generate six genotypes, viz, E2/E2, E2/E3, E3/E3, E3/E4, E4/E4, and E2/E4. APOE polymorphisms are associated with all types of tumors and cardiovascular diseases (CVD). However, the relationship between the type of APOE polymorphisms and tumorigenesis remains debatable. Therefore, we aimed to investigate the role of APOE polymorphisms on the tumor with or without CVD in southern China. METHODS: A total of 1438 participants were categorized into 4 groups: 409 patients with tumor, 369 patients with CVD, 338 patients with both tumor and CVD, and 322 controls. APOE polymorphisms were determined by genotyping assay. The factors influencing tumor patients with or without CVD were also analyzed by logistic regression analysis. RESULTS: The present study involved different types of solid tumors. Lung cancer was the most common cancer (20.2%, 151/747), followed by colorectal (17%, 127/747), esophageal (9.8%, 73/747), and liver (8.7%, 65/747) cancers. E3/E3 was the most frequent genotype, and É3 was the greatest allele frequency in our study population. The frequencies of the E3/E3, E3/E4, E2/E3, E2/E4, E4/E4, and E2/E2 genotypes in tumor patients were 76.97% (575/747), 14.19% (106/747), 6.83% (51/747), 1.2% (9/747), 0.4% (3/747), and 0.4% (3/747), respectively. Tumor patients carrying ε3 with or without CVD showed higher levels of TG, TC, and LDL-C and lower levels of HDL-C compared to the controls carrying ε3. On the other hand, the tumor patients carrying ε4 with or without CVD showed higher levels of TG and LDL-C and lower levels of HDL-C (all P < 0.05). The frequency of APOE ε4 allele and the E3/E4 genotype was relatively greater in tumor or CVD patients (P < 0.001). In addition, ε4 allele acted as an independent risk factor for tumor patients group (P = 0.037, adjusted OR = 1.92, 95% CI 1.04-3.55) and tumor + CVD patients group (P = 0.012, adjusted OR = 2.53, 95% CI 1.22-5.23). CONCLUSIONS: Individuals carrying ε4 are at a higher risk of tumor with or without CVD, and APOE polymorphisms affect the serum lipid profiles.
Assuntos
Apolipoproteínas E/genética , Doenças Cardiovasculares , Alelos , Carcinogênese/genética , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , LDL-Colesterol/genética , Predisposição Genética para Doença , Genótipo , HumanosRESUMO
BACKGROUND: Apolipoprotein E (APOE) is involved in the pathogenesis of atherosclerosis and conveys a higher risk of coronary artery disease (CAD). The aim of the present study was to investigate the possible association between APOE gene polymorphism and the risk of CAD in postmenopausal Hakka women in southern China. METHODS: The APOE genotypes of 653 CAD patients and 646 control participants were determined by the polymerase chain reaction (PCR) and hybridization to a Sinochip. RESULTS: The prevalence of each APOE genotype differed between CAD patients and control participants (P = 0.011). The E3/E3 genotype was the most common and the E2/E2 genotype was the least common in the study sample. Moreover, the presence of ε4 allele was associated with higher serum concentrations of triglycerides (TG), total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C), and lower concentration of high-density lipoprotein-cholesterol (HDL-C). Multiple logistic regression analysis revealed that participants with ε4 allele have a significantly higher risk of CAD after adjustment for the presence of diabetes mellitus and hypertension, and their serum uric acid, TC, and LDL-C concentrations (adjusted odds ratio (OR) 1.50, 95% confidence interval (CI) 1.10-2.05, P = 0.010). CONCLUSIONS: The present results suggest that APOE polymorphism is associated with a higher risk of CAD in postmenopausal Hakka women in southern China.
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Apolipoproteínas E/genética , Doença da Artéria Coronariana/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Idoso , Alelos , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/patologia , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Triglicerídeos/sangueRESUMO
BACKGROUND: The aim of this study was to investigate the infection and antimicrobial resistance of Ureaplasma urealyticum and Mycoplasma hominis in patients with genitourinary symptoms among Hakka population in Meizhou, China. METHODS: A total of 12 633 females and 3315 males who presented urogenital symptoms and were subjected to mycoplasma tests from 2014 to 2018 were enrolled in this study. The mycoplasma detection and antimicrobial susceptibility were tested using the Mycoplasma ID/AST kit. RESULTS: The total incidence of mycoplasma infection, as well as the incidence of U urealyticum in Hakka population was annually increasing from 2014 to 2018. The total incidences and U urealyticum infection were more prevalent in females than males. Higher positive rate of mycoplasmas infection was observed in women aged 16-20 (50.9%) and men aged 26-30 (25.4%). The occurrence of antimicrobial resistance of mycoplasma to antibacterial agents remained relatively similar in the past five years. Ureaplasma urealyticum infection, M hominis infection, and co-infection of resistance to levofloxacin, erythromycin, ciprofloxacin, ofloxacin, roxithromycin, azithromycin, clarithromycin, and sparfloxacin were dramatically higher in females than in males. CONCLUSION: Our findings indicate a high burden of mycoplasmas infection and antimicrobial resistance of mycoplasmas infection among females, and josamycin and minocycline may be recommended as the primary choice in clinical treatment of anti-mycoplasmas.
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Infecções por Mycoplasma/epidemiologia , Mycoplasma hominis/efeitos dos fármacos , Infecções do Sistema Genital/epidemiologia , Infecções por Ureaplasma/epidemiologia , Ureaplasma urealyticum/efeitos dos fármacos , Adolescente , Adulto , Distribuição por Idade , Antibacterianos/farmacologia , China/epidemiologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Feminino , Humanos , Incidência , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Infecções por Mycoplasma/microbiologia , Prevalência , Infecções do Sistema Genital/microbiologia , Adulto JovemRESUMO
BACKGROUND: It is necessary to investigate the frequency of BRCA1 and BRCA2 mutations in Hakka populations due to the variations in breast cancer epidemiology and genetics. METHODS: 359 breast cancer patients and 66 ovarian cancer patients were included in this retrospective clinical study. Mutations of BRCA1 and BRCA2 were detected in blood samples by semiconductor sequencing. RESULTS: The sensitivity of tumor markers including CEA, CA15-3, CA12-5, and CA199 for screening breast cancer was 16.44, 15.11, 8.44, and 7.56%, the combination of these 4 tumor markers reached the highest sensitivity index (31.11%). For ovarian cancer, the tumor markers were CA12-5 (54.05%), HE-4 (54.05%), CA72-4 (51.35%), and CEA (2.70%) in order of decreasing sensitivity. Moreover, the combination of these 4 tumor markers has the best sensitivity (75.68%) for screening ovarian cancer. In breast cancer patients, we found 5 (1.39%) patients with mutations in BRCA1, 13 (3.62%) mutations in BRCA2, and the total carrier rate is 5.01% (18/359). For ovarian cancer patients, the corresponding results were 3 (4.54%) mutations, 2 (3.03%) mutations, and 7.58% (5/66), respectively. The proportion of BRCA mutations was 5.41% (23/425) in breast and ovarian cancer patients of a Hakka population. The pathogenic, likely pathogenic, and benign mutations, and mutations of uncertain significance in this study mainly occurred in exon 14 of the BRCA1 gene, and exon 10 and exon 11 of the BRCA2 gene. CONCLUSIONS: Understanding the spectrum and frequency of BRCA1 and BRCA2 mutations in a Hakka population will assist in the prevention and control of hereditary breast and ovarian cancers in this population.
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N6-methyladenosine (m6A) is the most prevalent mRNA modification in higher eukaryotes. Recent studies suggest that m6A has a regulatory role in mRNA degradation and translation initiation or efficiency, involving in cell fate determination in yeast, plants, and stem cells of mammalian. Trypanosoma brucei (T. brucei) regulates gene expression through post-transcriptional fashion, which heavily relies on mRNA cis-motifs. However, internal mRNA modification in T. brucei has not been reported yet. Here we found m6A modification is abundant in T. brucei and presented a transcriptome wide methylome of m6A in both life stages of T. brucei. We identified 355 and 95 peaks in procyclic form and blood stream form trypanosomes respectively. A consensus motif of CAU was shared in both life stages of T. brucei. mRNA abundance of m6A-containing genes is higher in procyclic form and tend to be down-regulated in bloodstream form trypanosomes. Furthermore, m6A-containing transcripts harbor relative longer half-lives, and are enriched in pathways of cell morphology and movement in procyclic form trypanosomes. By m6A-containing RNA pulldown in both life stages, we identified TRRM2 as a potential m6A reader in T. brucei. Uncovering the m6A methylome and its binding proteins may provide a new post-transcriptional regulatory pathway in T. brucei.
Assuntos
Adenosina/análogos & derivados , Metilação de DNA/genética , Estágios do Ciclo de Vida/genética , Trypanosoma brucei brucei/crescimento & desenvolvimento , Trypanosoma brucei brucei/genética , Adenosina/metabolismo , Sequência de Bases , Linhagem Celular , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Proteínas de Protozoários/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/genéticaRESUMO
The multisubunit eukaryotic initiation factor 3 (eIF3) plays multiple roles in translation but is poorly understood in trypanosomes. The putative subunits eIF3a and eIF3f of Trypanosoma brucei (TbIF3a and TbIF3f) were overexpressed and purified, and 11 subunits were identified, TbIF3a through l minus j, which form a tight complex. Both TbIF3a and TbIF3f are essential for the viability of T. brucei RNAi knockdown of either of them severely reduced total translation and the ratio of the polysome/80S peak area. TbIF3f and TbIF3a RNAi cell lines were modified to express tagged-TbIF3a and -TbIF3f, respectively. RNAi in combination with affinity purification assays indicated that both subunits are variably required for TbIF3 stability and integrity. The relative abundance of other subunits in the TbIF3f-tag complex changed little upon TbIF3a depletion; while only subunits TbIF3b, i, and e copurified comparably with TbIF3a-tag upon TbIF3f depletion. A genome-wide UV-crosslinking assay showed that several TbIF3 subunits have direct RNA-binding activity, with TbIF3c showing the strongest signal. In addition, CrPV IRES, but neither EMCV IRES nor HCV IRES, was found to mediate translation in T. brucei These results together imply that the structure of TbIF3 and the subunits function have trypanosome-specific features, although the composition is evolutionarily conserved.
Assuntos
Fator de Iniciação 3 em Eucariotos/genética , Biossíntese de Proteínas , Subunidades Proteicas/genética , Proteínas de Protozoários/genética , RNA de Protozoário/genética , Trypanosoma brucei brucei/genética , Sequência de Aminoácidos , Sequência Conservada , Dicistroviridae/genética , Vírus da Encefalomiocardite/genética , Fator de Iniciação 3 em Eucariotos/antagonistas & inibidores , Fator de Iniciação 3 em Eucariotos/química , Fator de Iniciação 3 em Eucariotos/metabolismo , Regulação da Expressão Gênica , Hepacivirus/genética , Sítios Internos de Entrada Ribossomal , Ligação Proteica , Estabilidade Proteica , Subunidades Proteicas/antagonistas & inibidores , Subunidades Proteicas/química , Subunidades Proteicas/metabolismo , Proteínas de Protozoários/antagonistas & inibidores , Proteínas de Protozoários/química , Proteínas de Protozoários/metabolismo , RNA de Protozoário/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Ribossomos/genética , Ribossomos/metabolismo , Trypanosoma brucei brucei/crescimento & desenvolvimento , Trypanosoma brucei brucei/metabolismo , Raios UltravioletaRESUMO
Uridine insertion and deletion RNA editing generates functional mitochondrial mRNAs in Trypanosoma brucei. The mRNAs are differentially edited in bloodstream form (BF) and procyclic form (PF) life cycle stages, and this correlates with the differential utilization of glycolysis and oxidative phosphorylation between the stages. The mechanism that controls this differential editing is unknown. Editing is catalyzed by multiprotein â¼20S editosomes that contain endonuclease, 3'-terminal uridylyltransferase, exonuclease, and ligase activities. These editosomes also contain KREPB5 and KREPA3 proteins, which have no functional catalytic motifs, but they are essential for parasite viability, editing, and editosome integrity in BF cells. We show here that repression of KREPB5 or KREPA3 is also lethal in PF, but the effects on editosome structure differ from those in BF. In addition, we found that point mutations in KREPB5 or KREPA3 differentially affect cell growth, editosome integrity, and RNA editing between BF and PF stages. These results indicate that the functions of KREPB5 and KREPA3 editosome proteins are adjusted between the life cycle stages. This implies that these proteins are involved in the processes that control differential editing and that the 20S editosomes differ between the life cycle stages.
Assuntos
Estágios do Ciclo de Vida , Proteínas de Protozoários/metabolismo , Edição de RNA , Trypanosoma brucei brucei/crescimento & desenvolvimento , Trypanosoma brucei brucei/genética , Motivos de Aminoácidos , Sequência de Aminoácidos , Sangue/parasitologia , Linhagem Celular , Resistência a Medicamentos/genética , Estágios do Ciclo de Vida/efeitos dos fármacos , Modelos Moleculares , Dados de Sequência Molecular , Mutação , Estrutura Terciária de Proteína , Proteínas de Protozoários/química , Proteínas de Protozoários/genética , Ribonuclease III/química , Ribonuclease III/metabolismo , Tetraciclina/farmacologia , Trypanosoma brucei brucei/efeitos dos fármacos , Trypanosoma brucei brucei/metabolismoRESUMO
Interleukin-7 (IL-7) has been used as an immunoregulatory and latency-reversing agent in human immunodeficiency virus type 1 (HIV-1) infection. Although IL-7 can restore circulating CD4(+) T cell counts in HIV-1-infected patients, the anti-apoptotic and proliferative effects of IL-7 appear to benefit survival and expansion of HIV-1-latently infected memory CD4(+) T lymphocytes. IL-7 has been shown to elevate CD95 on CD4(+) T cells in HIV-1-infected individuals and prime CD4(+) T lymphocytes to CD95-mediated proliferative or apoptotic signals. Here we observed that through increasing microRNA-124, IL-7 down-regulates the splicing regulator polypyrimidine tract binding protein (PTB), leading to inclusion of the transmembrane domain-encoding exon 6 of CD95 mRNA and, subsequently, elevation of CD95 on memory CD4(+) T cells. Moreover, IL-7 up-regulates cellular FLICE-like inhibitory protein (c-FLIP) and stimulates c-Jun N-terminal kinase (JNK) phosphorylation, which switches CD95 signaling to survival mode in memory CD4(+) T lymphocytes. As a result, co-stimulation through IL-7/IL-7R and FasL/CD95 signal pathways augments IL-7-mediated survival and expansion of HIV-1-latently infected memory CD4(+) T lymphocytes. Collectively, we have demonstrated a novel mechanism for IL-7-mediated maintenance of HIV-1 reservoir.
Assuntos
Processamento Alternativo , Linfócitos T CD4-Positivos/virologia , Infecções por HIV/genética , Interleucina-7/genética , MicroRNAs/genética , Proteína de Ligação a Regiões Ricas em Polipirimidinas/genética , Receptor fas/genética , Sequência de Bases , Linfócitos T CD4-Positivos/imunologia , Proliferação de Células , Sobrevivência Celular , Regulação da Expressão Gênica , Infecções por HIV/imunologia , Infecções por HIV/metabolismo , Infecções por HIV/virologia , HIV-1/imunologia , Interações Hospedeiro-Patógeno , Humanos , Memória Imunológica , Interleucina-7/imunologia , MicroRNAs/imunologia , Dados de Sequência Molecular , Proteína de Ligação a Regiões Ricas em Polipirimidinas/imunologia , Cultura Primária de Células , Receptores de Interleucina-7/genética , Receptores de Interleucina-7/imunologia , Transdução de Sinais , Carga Viral , Replicação Viral , Receptor fas/imunologiaRESUMO
BACKGROUND: A lot of microRNAs (miRNAs) derived from viral genomes have been identified. Many of them play various important roles in virus replication and virus-host interaction. Cellular miRNAs have been shown to participate in the regulation of HIV-1 viral replication, while the role of viral-encoded miRNAs in this process is largely unknown. RESULTS: In this report, through a strategy combining computational prediction and deep sequencing, we identified a novel HIV-1-encoded miRNA, miR-H3. MiR-H3 locates in the mRNA region encoding the active center of reverse transcriptase (RT) and exhibits high sequence conservation among different subtypes of HIV-1 viruses. Overexpression of miR-H3 increases viral production and the mutations in miR-H3 sequence significantly impair the viral replication of wildtype HIV-1 viruses, suggesting that it is a replication-enhancing miRNA. MiR-H3 upregulates HIV-1 RNA transcription and protein expression. A serial deletion assay suggests that miR-H3 targets HIV-1 5' LTR and upregulates the promoter activity. It interacts with the TATA box in HIV-1 5' LTR and sequence-specifically activates the viral transcription. In addition, chemically-synthesized small RNAs targeting HIV-1 TATA box activate HIV-1 production from resting CD4+ T cells isolated from HIV-1-infected patients on suppressive highly active antiretroviral therapy (HAART). CONCLUSIONS: We have identified a novel HIV-1-encoded miRNA which specifically enhances viral production and provide a specific method to activate HIV-1 latency.
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Regulação Viral da Expressão Gênica , HIV-1/fisiologia , MicroRNAs/metabolismo , TATA Box , Replicação Viral , Doadores de Sangue , Transcriptase Reversa do HIV/genética , Transcriptase Reversa do HIV/metabolismo , HIV-1/genética , HumanosRESUMO
Three distinct editosomes are required for the uridine insertion/deletion editing that creates translatable mitochondrial mRNAs in Trypanosoma brucei. They contain KREPB6, KREPB7, or KREPB8 proteins and their respective endonucleases KREN3, KREN2, or KREN1. RNAi knockdowns of KREPB6, KREPB7, and KREPB8 variably affect growth and RNA editing. KREPB6 and KREPB7 knockdowns substantially reduced in vitro insertion site cleavage activity of their respective editosomes, while KREPB8 knockdown did not affect its editosome deletion site cleavage activity despite inhibition of growth and editing. KREPB6, KREPB7, and KREPB8 knockdowns disrupted tagged KREN3, KREN2, or KREN1 editosomes, respectively, to varying degrees, and in the case of KREN1 editosomes, the deletion editing site cleavage activity shifted to a smaller S value. The varying effects correlate with a combination of the relative abundances of the KREPB6-8 proteins and of the different insertion and deletion sites. Tagged KREPB6-8 were physically associated with deletion subcomplexes upon knockdown of the centrally interactive KREPA3 protein, while KREN1-3 endonucleases were associated with insertion subcomplexes. The results indicate that KREPB6-8 occupy similar positions in editosomes and are important for the activity and specificity of their respective endonucleases. This suggests that they contribute to the accurate recognition of the numerous similar but diverse editing site substrates.
Assuntos
Endonucleases/genética , Endonucleases/metabolismo , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Edição de RNA , Trypanosoma brucei brucei/genética , Trypanosoma brucei brucei/metabolismo , Técnicas de Silenciamento de Genes/métodos , Mutagênese Insercional , Regiões Promotoras Genéticas , RNA Mensageiro/genética , RNA Mitocondrial , RNA de Protozoário/genética , Trypanosoma brucei brucei/enzimologia , Trypanosoma brucei brucei/crescimento & desenvolvimento , Uridina/metabolismoRESUMO
Nuclear factor-κB (NF-κB) is an important transcription factor. While the NF-κB signaling pathway is modulated by many microRNAs (miRNAs), very few have been reported to target NF-κB1 gene directly. In this study, we used multiple miRNA target prediction programs to predict miRNAs with putative NF-κB1 3'-untranslated region (UTR) binding sites. miR-183 was strongly implicated and experimentally validated by reporter assays. The results showed a reduced expression of the NF-κB1 3'UTR containing luciferase vector by â¼30%, which was comparable to the reduction by miR-9 (the only known miRNA targeting the NF-κB1 3'UTR). Mutagenesis of the miR-183 seed region binding sequence in the NF-κB1 3'UTR abolished the inhibitory effect of miR-183, as noted by the NF-κB1 3'UTR-containing reporter. Moreover, similar to miR-9, miR-183 could down-regulate the expression of the reporter driven by NF-κB promoter to some degree, suggesting that miR-183 might negatively regulate the endogenous NF-κB1. Overall, our data provide computational and experimental evidence that NF-κB1 is a potential target of miR-183.
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Regiões 3' não Traduzidas , MicroRNAs/genética , MicroRNAs/metabolismo , Subunidade p50 de NF-kappa B/antagonistas & inibidores , Subunidade p50 de NF-kappa B/genética , Sequência de Bases , Sítios de Ligação/genética , Regulação para Baixo , Genes Reporter , Células HEK293 , Humanos , Luciferases/genética , Regiões Promotoras Genéticas , Transdução de Sinais , SoftwareRESUMO
Pseudogenes have been shown to acquire unique regulatory roles from more and more organisms. We report the observation of a cluster of siRNAs derived from pseudogenes of African Trypanosoma brucei using high through-put analysis. We show that these pseudogene-derived siRNAs suppress gene expression through RNA interference. The discovery that siRNAs may originate from pseudogenes and regulate gene expression in a unicellular eukaryote provides insights into the functional roles of pseudogenes and into the origin of noncoding small RNAs.
Assuntos
Regulação da Expressão Gênica/genética , Pseudogenes/genética , RNA Interferente Pequeno/genética , Trypanosoma brucei brucei/genética , Genes de ProtozoáriosRESUMO
Background: The role of aldehyde dehydrogenase 2 (ALDH2) in cardiovascular diseases has been gradually studied. However, it is unclear whether ALDH2 polymorphism is associated with the risk of early onset (onset age ≤55 years old in men and ≤65 years old in women) coronary artery stenosis (CAS). The association between ALDH2 single nucleotide polymorphism (SNP) rs671 and risk in patients with early onset CAS was investigated in this study. Methods: The study included 213 early onset CAS patients and 352 individuals without CAS were set as controls. The ALDH2 rs671 polymorphism was genotyped by polymerase chain reaction (PCR) - microarray. Differences in ALDH2 rs671 genotypes and alleles between patients and controls were compared. Multiple logistic regression analysis was performed after adjusting for gender, body mass index (BMI), smoking history, drinking history, and diabetes mellitus to assess the relationship between ALDH2 rs671 genotypes and early onset CAS risk. Results: The frequency of the ALDH2 rs671 G/G genotype was lower in the early onset CAS patients (43.7% vs 55.3%, p=0.007) than that in the controls. The frequency of the ALDH2 rs671 A allele was higher (32.9% vs 25.0%) than that in the controls (p=0.005). After adjusting for other confounding factors, multivariate logistic regression showed that ALDH2 rs671 A/A genotype (A/A vs G/G: odds ratio (OR) 2.508, 95% confidence interval (CI): 1.130-5.569, p=0.024), overweight (BMI≥24.0 vs 18.5-23.9: OR 5.047, 95% CI: 3.275-7.777, p<0.001), history of smoking (yes vs no: OR 2.813, 95% CI: 1.595-4.961, p<0.001), and diabetes mellitus (yes vs no: OR 2.191, 95% CI: 1.397-3.437, p=0.001) were the independent risk factors of early onset CAS. Conclusion: In men ≤55 years old and women ≤65 years old, individuals with ALDH2 rs671 A/A genotype, overweight (BMI ≥24.0 kg/m2), smoking history, and diabetes mellitus increased risk of developing CAS.
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Perovskite solar cells (PSCs) have attracted widespread research and commercialization attention because of their high power conversion efficiency (PCE) and low fabrication cost. The long-term stability of PSCs should satisfy industrial requirements for photovoltaic devices. Inverted PSCs with a p-i-n architecture exhibit considerable advantages because of their excellent stability and competitive efficiency. The continuously broken-through PCE of inverted PSCs shows huge application potential. This review summarizes the developments and outlines the characteristics of inverted PSCs including charge transport layers (CTLs), perovskite compositions, and interfacial regulation strategies. The latest effective CTLs, interfacial modification, and stability promotion strategies especially under light, thermal, and bias conditions are emphatically analyzed. Furthermore, the applications of the inverted structure in high-efficiency and stable tandem, flexible photovoltaic devices, and modules and their main obstacles are systematically introduced. Finally, the remaining challenges faced by inverted devices are discussed, and several directions for advancing inverted PSCs are proposed according to their development status and industrialization requirements.
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Enterovirus 71 (EV71) is the common causative agent of hand-foot-mouth disease (HFMD). Despite evidence in mice model suggested that the interferon (IFN) signaling pathways play a role in defending against this virus, knowledge on the IFN-mediated antiviral response is still limited. Here we identified an IFN-stimulated gene (ISG) called L3HYPDH, whose expression inhibits EV71 replication. Mapping assay indicated that amino acids 61-120 and 295-354 are critical for its optimal antiviral activity. Mechanismly, L3HYPDH specifically inhibits protein translation mediated by EV71 internal ribosome entry site (IRES). Our data thus uncovered a new mechanism utilized by the host cell to restrict EV71 replication.
Assuntos
Doença de Mão, Pé e Boca , Interferons , Animais , Camundongos , RNA , Aminoácidos , AntiviraisRESUMO
The p- or n-type property of semiconductor materials directly determine the final performance of photoelectronic devices. Generally, perovskite deposited on p-type substrate tends to be p-type, while perovskite deposited on n-type substrate tends to be n-type. Motived by this, a substrate-induced re-growth strategy is reported to induce p- to n-transition of perovskite surface in inverted perovskite solar cells (PSCs). p-type perovskite film is obtained and crystallized on p-type substrate first. Then an n-type ITO/SnO2 substrate with saturated perovskite solution is pressed onto the perovskite film and annealed to induce the secondary re-growth of perovskite surface region. As a result, p- to n-type transition happens and induces an extra junction at perovskite surface region, thus enhancing the built-in potential and promoting carrier extraction in PSCs. Resulting inverted PSCs exhibit high efficiency of over 25% with good operational stability, retaining 90% of initial efficiency after maximum power point (MPP) tracking for 800 h at 65 °C with ISOS-L-2 protocol.
RESUMO
Tandem amplification of carbapenemase genes increases gene copy number and enhances carbapenem resistance. These amplifications are often heterogeneous, transient, and located on plasmids, which also contribute to heteroresistance. Amplification of encoding genes is especially important for enzymes with low hydrolysis activity, which are often overlooked. Here, we reported an intrinsic oxacillinase oxaAb amplification flanked by ISAba1. The amplification is in the chromosome and contains up to 25 repeats. We provided genomic, transcriptomic, and proteomic evidence that the amplification resulted in oxacillinase overproduction. Notably, no point mutations of oxaAb were found during the amplification process. Strains of Acinetobacter baumannii with intrinsic amplified or external transformed ISAba1-oxaAb exhibited higher meropenem hydrolysis activity. Furthermore, the number of repeats in the amplification decreased gradually over a period of 21 d cultured with carbapenem withdrawal. However, upon re-exposure to meropenem, the ISAba1 flanked oxaAb responded rapidly, with repeat numbers reaching or exceeding pre-carbapenem withdrawal levels within 24 h. Taken together, these findings suggest that ISAba1-mediated gene amplification and overproduction of intrinsic low-activity oxacillinase oxaAb resulted in carbapenem resistance.
Assuntos
Acinetobacter baumannii , Antibacterianos , Carbapenêmicos , beta-Lactamases , Acinetobacter baumannii/genética , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/enzimologia , beta-Lactamases/genética , Carbapenêmicos/farmacologia , Antibacterianos/farmacologia , Amplificação de Genes , Testes de Sensibilidade Microbiana , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Cromossomos Bacterianos/genética , Humanos , Meropeném/farmacologia , Elementos de DNA Transponíveis/genéticaRESUMO
BACKGROUND: Surveillance systems revealed that the prevalence of vancomycin-resistant Enterococcus faecium (VREfm) has increased. We aim to investigate the epidemiological and genomic characteristics of VREfm in China. METHODS: We collected 20,747 non-redundant E. faecium isolates from inpatients across 19 hospitals in six provinces between January 2018 and June 2023. VREfm was confirmed by antimicrobial susceptibility testing. The prevalence was analyzed using changepoint package in R. Genomic characteristics were explored by whole-genome sequencing. RESULTS: 5.59% (1159/20,747) of E. faecium isolates were resistant to vancomycin. The prevalence of VREfm increased in Guangdong province from 5% before 2021 to 20-50% in 2023 (p < 0.0001), but not in the other five provinces. Two predominant clones before 2021, ST17 and ST78, were substituted by an emerging clone, ST80, from 2021 to 2023 (88.63%, 195/220). All ST80 VREfm from Guangdong formed a single lineage (SC11) and were genetically distant from the ST80 VREfm from other countries, suggesting a regional outbreak. All ST80 VREfm in SC11 carried a new type of plasmid harbouring a vanA cassette, which was embedded in a Tn1546-like structure flanked by IS1678 and ISL3. However, no conjugation-related gene was detected and no transconjugant was obtained in conjugation experiment, indicating that the outbreak of ST80 VREfm could be attributed to clonal transmission. CONCLUSIONS: We revealed an ongoing outbreak of ST80 VREfm with a new vanA-harbouring plasmid in Guangdong, China. This clone has also been identified in other provinces and countries, foreboding a risk of wider spreading shortly. Continuous surveillance is needed to inform public health interventions.