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Influenced by water injection, a dominant flow channel is easily formed in the high water cut stage of a conglomerate reservoir, resulting in the inefficient or ineffective circulation of the injected water. With gel flooding as one of the effective development methods to solve the above problems, its parameter optimization determines its final development effect, which still faces great challenges. A new optimization method for gel flooding is proposed in this paper. Firstly, the gel flooding parameters were obtained through physical experiments; then, an experimental model of gel flooding was established according to the target reservoir, and parameter sensitivity analysis was carried out. Next, a history matching of the gel flooding experiment was carried out. Finally, history matching of the target reservoir was also carried out, and a gel flooding scheme was designed and optimized to determine the best parameters. The experimental results showed that the gelation time was 4 h and the gel viscosity was 6332 mPa·s; the breakthrough pressure, resistance factor (RF), and residual resistance factor (RRF) all decreased with the increase in permeability. The gel had a good profile control ability and improved oil recovery by 16.40%. The numerical simulation results illustrated that the porosity of the high permeability layer (HPL) had the greatest impact on the cumulative oil production (COP) of the HPL, and the maximum polymer adsorption value of the HPL had the largest influence on the COP of the low permeability layer (LPL) and the water cut of both layers. Benefiting from parameter sensitivity analysis, history matching of the gel flooding experiment and a conglomerate reservoir in the Xinjiang A Oilfield with less time consumed and good quality was obtained. The optimization results of gel flooding during the high water cut stage in a conglomerate reservoir of the Xinjiang A Oilfield were as follows: the gel injection volume, injection rate, and polymer concentration were 2000 m3, 50 m3/d, and 2500 mg/L, respectively. It was predicted that the water cut would decrease by 6.90% and the oil recovery would increase by 2.44% in two years. This paper not only provides a more scientific and efficient optimization method for gel flooding in conglomerate reservoirs but also has important significance for improving the oil recovery of conglomerate reservoirs.
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microRNA-663a (miR-663a) was reported to be highly expressed in cancers. However, its roles in melanoma progression remain unclear. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was conducted to measure miR-663a expression level in melanoma cell lines and normal cells. Cell counting kit-8 assay, wound-healing assay, and transwell invasion assay were conducted to analyze biological roles of miR-663a in melanoma. Luciferase activity reporter assay was conducted to validate the connection of miR-663a and Four and a half LIM domain (FHL) protein 3 (FHL3) in melanoma. Our results showed miR-663a expression level was significantly increased in melanoma cells compared with normal cells. Silencing miR-663a expression suppresses melanoma cell proliferation, migration, and invasion in vitro. Moreover, FHL3 was validated as a functional target of miR-663a. Knockdown of FHL3 partially rescued the inhibitory effects of miR-663a inhibitor on melanoma cell behaviors. Together, our work provided evidence that miR-663a functions as an oncogenic miRNA in melanoma.
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Alport syndrome (AS) is a hereditary progressive nephropathy characterized by hematuria, ultrastructural lesions of the glomerular basement membrane, ocular lesions and sensorineural hearing loss. Germline mutations of COL4A5 are associated with X-linked AS with an extreme phenotypic heterogeneity. Here, we investigated a Chinese family with Alport syndrome. The proband was a 9-year-old boy with hematuria and proteinuria. Based on the test results of renal biopsy and immunofluorescence, the proband was initially diagnosed as IgA nephropathy and the treatment was recommended accordingly. Meanwhile, we found that the treatment outcome was poor. Therefore, for proper clinical diagnosis and appropriate treatment, targeted exome-based next-generation sequencing has been undertaken. We identified a novel hemizygous single nucleotide deletion c.1902delA in COL4A5 gene. Segregation analysis identified that this novel mutation is co-segregated among the affected family members but absent in unaffected family members. The clinical diagnosis of the proband was revised as AS accompanied by IgA nephropathy, which has been rarely reported. Our findings demonstrated the significance of the application of Genetic screening, expanded the mutation spectrum of COL4A5 associated AS patients with atypical renal phenotypes and provided a good lesson to be learned from our detour during the diagnosis.
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Colágeno Tipo IV/genética , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/genética , Nefrite Hereditária/diagnóstico , Nefrite Hereditária/genética , Povo Asiático/genética , Criança , Simulação por Computador , Análise Mutacional de DNA , Exoma/genética , Família , Deleção de Genes , Testes Genéticos/métodos , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Mutação , FenótipoRESUMO
The absorption of nutrients and disease resistance are two indispensable physiological processes in plants; however, it is still largely unknown whether there is cross-talk between their molecular signaling pathways. In this study, we identified the rice OsPT8 protein, which is a member of the phosphate transporters (PTs) Pht1 family and also plays a role in rice disease resistance. The transcriptional level of OsPT8 is suppressed after infection with rice pathogens and treatment with pathogen-associated molecular patterns (PAMPs). Overexpression of OsPT8 suppresses rice disease resistance against the pathogens Magnaporthe oryzae and Xanthomonas oryzae pv. oryzae. Accordingly, the transcription level of resistance related genes, such as PAL and PBZ1, is inhibited in plants overexpressing OsPT8 (OsPT8-OX) after inoculation with these pathogens. In OsPT8-OX plants, PAMPs-triggered immunity (PTI) response genes, such as OsRac1 and SGT1, are suppressed during treatment with PAMPs chitin or flg22. Moreover, the typical response of PTI is suppressed after chitin or flg22 treatment. We also identified OsPT8 as an interactor of a rice mitogen-activated protein kinase BWMK1, which is a regulator of disease resistance. Under low phosphate (Pi) conditions, the OsPT8-OX plants display better agronomic traits than the control plants. However, the differences in development between OsPT8-OX and the control plants are reduced upon the increase of Pi concentration. These results demonstrate that OsPT8 regulates the transduction of Pi signaling for development and negatively regulates rice immunity.
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Resistência à Doença/genética , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica de Plantas , Oryza/genética , Proteínas de Transporte de Fosfato/genética , Doenças das Plantas/genética , Proteínas de Plantas/genética , Interações Hospedeiro-Patógeno , Magnaporthe/fisiologia , Oryza/crescimento & desenvolvimento , Oryza/microbiologia , Proteínas de Transporte de Fosfato/metabolismo , Fosfatos/metabolismo , Doenças das Plantas/microbiologia , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Ligação Proteica , Transdução de Sinais , Xanthomonas/fisiologiaRESUMO
OBJECTIVES: Thalassemia is a highly prevalent monogenic inherited disease in southern China. It is important to collect epidemiological data comprehensively for proper prevention and treatment. METHODS: In this study, blood samples collected from 15 807 residents of Chenzhou were primarily screened by hematological tests. A total of 3973 samples of suspected thalassemia carriers were further characterized by combined next-generation sequencing (NGS) and Gap-PCR. RESULTS: In total, 1704 subjects were diagnosed as thalassemia carriers with a total prevalence rate of 10.78%, including 943 α-thalassemia carriers, 708 ß-thalassemia carriers, and 53 composite α and ß-thalassemia carriers. The prevalence rates of α-thalassemia, ß-thalassemia, and composite α and ß-thalassemia were 5.97%, 4.48%, and 0.34%, respectively. Meanwhile, we characterized 19 α-thalassemia variations and 21 ß-thalassemia variations in thalassemia carriers. Approximately 2.88% of thalassemia carriers would be missed by traditional genetic analysis. In addition, four novel thalassemia mutations and one novel abnormal hemoglobin mutation were identified. CONCLUSIONS: Our data suggest a high prevalence of thalassemia and a diverse spectrum of thalassemia-associated variations in Chenzhou. Also, combined NGS and Gap-PCR is an effective thalassemia screening method. Our findings might be helpful for prevention and treatment of thalassemia in this region.
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Talassemia alfa/epidemiologia , Talassemia alfa/genética , Talassemia beta/epidemiologia , Talassemia beta/genética , Adolescente , Adulto , Criança , Pré-Escolar , China/epidemiologia , Feminino , Triagem de Portadores Genéticos , Hemoglobinas Anormais/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Mutação , Reação em Cadeia da Polimerase/métodos , Adulto JovemRESUMO
Primary hyperoxaluria type 1 (PH1) is a rare metabolic disorder characterized by a defect in the liver-specific peroxisomal enzyme alanine-glyoxylate and serine-pyruvate aminotransferase (AGT). This disorder results in hyperoxaluria, recurrent urolithiasis, and nephrocalcinosis. Three forms of PH1 have been reported. Data on the infantile form of PH1 are currently limited in literature. Despite the fact that China is the most populated country in the world, only a few AGXT mutations have been reported in several Chinese PH1 patients. In the present study, we investigated a Chinese family in which two siblings are affected by the infantile form of PH1. Sanger sequencing was carried out on the proband, but the results were misleading. Two novel missense mutations (c.517T > C/p.Cys173Arg and c.667A > C/p.Ser223Arg) of the AGXT gene were successfully detected through whole-exome sequencing. These two mutations occurred in the highly conserved residues of the AGT. Four software programs predicted both mutations as the cause of the disease. A postmortem examination was performed and revealed the occurrence of global nephrocalcinosis on both kidneys. The crystals were collected and analyzed as calcium oxalate monohydrate. This study extends the knowledge on the clinical phenotype-genotype correlation of the AGXT mutation. That is, (i) two novel missense mutations were identified for the infantile form of PH1 and (ii) the same AGXT genotype caused the same infantile form of PH1 within the family.
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The present study describes the first prenatally diagnosed 46,XX testicular disorders of sex development (46,XX testicular DSD) case with DMD gene mutation by integrated analyses in a Chinese pedigree. Chromosome karyotype G-banding analysis of the proband showed a 46,XX karyotype, but B-ultrasound analysis demonstrated the existence of scrotum, testis and penis which inferred a male sexual differentiation. Aneuploidy and copy number variation (CNV) detection by low-coverage single-end whole genome sequencing (WGS) revealed a de novo SRY (sex-determining region Y) gene positive fragment of 224.34 kb length (chrY:2,649,472-2,873,810) which explained the gonadal/genital-chromosomal inconsistency in the proband. Additionally, targeted-region-capture-based DMD gene sequencing and Sanger verification confirmed a widely reported pathogenic heterozygous nonsense mutation (NM_004006, c.9100C>T, p.Arg3034Ter) in the dystrophin-coding gene named DMD. This study emphasizes that integrated analyses of the imaging results, cytogenetics, and molecular features can play an important role in prenatal diagnosis. It requires the combination of more detection techniques with higher resolution than karyotyping to determine the genetic and biological sex of fetuses in prenatal diagnosis. To conclusively determine both the biological and genetic sex of the fetus at the time of prenatal diagnosis particularly in cases that involve X-linked conditions is of vital importance, which would crucially influence the decision-making regarding abortions. This study will help in prenatal diagnosis of DMD in future, also providing a new perspective that enables the genetic diagnosis of sex reversal in pregnancy. Moreover, genetic counseling/analysis for early diagnosis and pre-symptom interventions are warranted.
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Neurofibromatosis type 1 (NF1) is an autosomal dominant, multi-system, neurocutaneous disorder, manifested with neurofibromas and Cafe´-au-lait spots. Germline mutations in NF1 gene are associated with Neurofibromatosis type 1. NF1 gene encodes neurofibromin, a RAS-specific GTPase activating protein. In our study, we present a clinical molecular study of four Chinese probands with NF1 from four unrelated families, showing extreme phenotypic variation with rare phenotype. In family 1, the proband is a 16 months old girl with multiple café-au-lait spots throughout her whole body. In family 2, the proband is a 6 months old girl with several café-au-lait spots mostly in her trunk and in lower limbs. In family 3, the proband is a 4 months old boy with several café-au-lait spots, tibial pseudarthrosis, and chronic iron deficiency anemia. In family 4, the proband is a 14 years old boy with multiple café-au-lait spots of variable sizes. Targeted exome capture based next generation sequencing and Sanger sequencing identified a novel mutation and three previously reported mutations in these four probands. These four mutations in NF1 gene were causing disease phenotypes in these four probands and was absent in unaffected family members and in healthy controls. According to the variant interpretation guideline of American College of Medical Genetics and Genomics (ACMG), these four mutations, are classified as "likely pathogenic". Our result expands the mutational spectrum of the NF1 gene associated with neurofibromatosis type1.
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Anemia/genética , Manchas Café com Leite/genética , Genes da Neurofibromatose 1 , Mutação , Neurofibromatose 1/genética , Pseudoartrose/genética , Tíbia/patologia , Adolescente , Anemia/patologia , Povo Asiático , Manchas Café com Leite/patologia , Análise Mutacional de DNA , Feminino , Humanos , Lactente , Masculino , Neurofibromatose 1/patologia , Linhagem , Fenótipo , Pseudoartrose/patologiaRESUMO
Phelan-McDermid syndrome is a neurodevelopmental disorder caused by the terminal deletion of chromosome 22 (22q13) followed by the loss of function of the SHANK3 gene. Various terminal deletions of chromosome 22q13 are associated with Phelan-McDermid with a spectrum of phenotypic severity. Here, we have done a clinical molecular study of a Chinese proband with Phelan-McDermid syndrome. Both the proband and her younger brother are associated with this syndrome while their parents are phenotypically normal. We used a karyotype in order to detect the genotype of the proband and her younger brother. We have also used whole genome low-coverage paired-end next generation sequencing to determine whether the parent is the carrier of translocation with terminal 22q13 deletions. We found that both proband and her younger brother are comprises of a novel deletion of 22q13.31q13.33, harboring genes were associated with several clinical phenotype such as severity of speech delay, neonatal hypotonia, delayed in age of walking, male genital anomalies, dysplastic toenails, large and fleshy hands, macrocephaly, short stature, facial asymmetry, and atypical reflexes. Probands and her younger brother inherited this translocation from their mother whereas their father is genotypically normal. In conclusion, our present study expands the deletion spectrum and report a novel deletion associated with Phelan-McDermid syndrome.
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Transtornos Cromossômicos/genética , Cromossomos Humanos Par 22 , Translocação Genética , Criança , China , Deleção Cromossômica , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/fisiopatologia , Transtornos Cromossômicos/psicologia , Cromossomos Humanos Par 22/genética , Ecocardiografia Doppler em Cores , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Hereditariedade , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Cariotipagem , Masculino , Linhagem , Fenótipo , Tomografia Computadorizada por Raios XRESUMO
We have developed a new method for non-invasive prenatal testing (NIPT) of paternally inherited fetal mutants for ß-thalassemia (ß-thal). Specially designed primer-introduced restriction analysis-polymerase chain reaction (PIRA-PCR) were used to detect four major mutations [IVS-II-654, HBB: c.316-197C > T; codon 17 (A > T), HBB: c.52A > T; -28 (A > G), HBB: c.-78A > G and codons 41/42 (-TTCT), HBB: c.126_129delCTTT] causing ß-thal in China. The PIRA-PCR assay was first tested in a series of mixed DNA with different concentrations and mixed proportions. Subsequently, this assay was further tested in 10 plasma DNA samples collected from pregnant women. In the DNA mixture simulation test, the PIRA-PCR assay was able to detect 3.0% target genomic DNA (gDNA) mixed in 97.0% wild-type gDNA isolated from whole blood. For plasma DNA testing, the results detected by PIRA-PCR assay achieved 100.0% consistency with those obtained from the amniocentesis analysis. This new method could potentially be used for NIPT of paternally inherited fetal mutants for ß-thal.