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The Wnt/ß-catenin signaling pathway plays a significant role in the control of osteoblastogenesis and bone formation. CXXC finger protein 5 (CXXC5) has been recently identified as a negative feedback regulator of osteoblast differentiation through a specific interaction with Dishevelled (Dvl) protein. It was reported that targeting the Dvl-CXXC5 interaction could be a novel anabolic therapeutic target for osteoporosis. In this study, complex structure of Dvl PDZ domain and CXXC5 peptide was simulated with molecular dynamics (MD). Based on the structural analysis of binding modes of MD-simulated Dvl PDZ domain with CXXC5 peptide and crystal Dvl PDZ domain with synthetic peptide-ligands, we generated two different pharmacophore models and applied pharmacophore-based virtual screening to discover potent inhibitors of the Dvl-CXXC5 interaction for the anabolic therapy of osteoporosis. Analysis of 16 compounds selected by means of a virtual screening protocol yielded four compounds that effectively disrupted the Dvl-CXXC5 interaction in the fluorescence polarization assay. Potential compounds were validated by fluorescence spectroscopy and nuclear magnetic resonance. We successfully identified a highly potent inhibitor, BMD4722, which directly binds to the Dvl PDZ domain and disrupts the Dvl-CXXC5 interaction. Overall, CXXC5-Dvl PDZ domain complex based pharmacophore combined with various traditional and simple computational methods is a promising approach for the development of modulators targeting the Dvl-CXXC5 interaction, and the potent inhibitor BMD4722 could serve as a starting point to discover or design more potent and specific the Dvl-CXXC5 interaction disruptors.
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Proteínas de Transporte/antagonistas & inibidores , Proteínas Desgrenhadas/antagonistas & inibidores , Simulação de Dinâmica Molecular , Ligação Competitiva , Proteínas de Transporte/química , Proteínas de Ligação a DNA , Bases de Dados de Compostos Químicos , Proteínas Desgrenhadas/química , Humanos , Ligantes , Domínios PDZ , Ligação Proteica , Fatores de Transcrição , Via de Sinalização WntRESUMO
This study was conducted to investigate disease-modifying antirheumatic drug (DMARD) utilization in Korean elderly patients with rheumatoid arthritis (RA). We used data from January 1, 2005 to June 30, 2006 from the Health Insurance Review and Assessment Service claims database. The study subjects were defined as patients aged 65 yr or older with at least two claims with a diagnosis of RA. DMARD use was compared by the patients' age-group, gender, medical service, and geographic divisions. The patterns of DMARD use in mono- and combination therapy were calculated. RA medication use was calculated by the number of defined daily doses (DDD)/1,000 patients/day. A total of 166,388 patients were identified during the study period. DMARD use in RA patients was 12.0%. The proportion of DMARD use was higher in the younger elderly, females, and patients treated in big cities. Hydroxychloroquine was the most commonly used DMARD in monotherapy, and most of the combination therapies prescribed it with methotrexate. DMARD use in elderly RA patients was noticeably low, although drug prescriptions showed an increasing trend during the study period, clinicians may need to pay more attention to elderly RA patients.
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Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Quimioterapia Combinada , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Metotrexato/uso terapêutico , Programas Nacionais de Saúde , Estudos Retrospectivos , Fatores SexuaisRESUMO
Pheochromocytoma is a tumor of the sympathetic nervous system, characterized by atypical symptoms and signs. Pheochromocytoma metastases can be found in various tissues and organs. However, synchronous metastasis at the initial diagnosis of pheochromocytoma is rare. The present study described a case with synchronous liver metastasis at the initial diagnosis of adrenal pheochromocytoma based on imaging findings. A 41-year-old woman presented with liver pain and fatigue for 1 month. Physical examination showed increased blood pressure and heart rate with sinus tachycardia. Laboratory examination revealed normal levels of liver tumor markers and increased levels of serum or urine epinephrine and norepinephrine. CT examination revealed a large cystic solid mass in the right lobe of the liver and right adrenal gland, and the solid part of the mass was enhanced after enhancement. The pathological diagnosis was pheochromocytoma of the right adrenal gland with liver metastasis. The patient underwent right hepatectomy and right adrenal tumor resection. During the postoperative follow-up, the patient's blood pressure and catecholamine levels were within the normal range. Three years after surgery, the CT examination revealed multiple liver metastases. Chemotherapy was administered to the patient. A year later, re-examination revealed an increase and enlargement of the metastases, and the mass of the right adrenal gland remained similar to the previous one. After 6 months of follow-up, the patient succumbed to recurrence and metastasis. Preoperative diagnosis of metastatic pheochromocytoma is challenging. This case mainly emphasizes that imaging findings can help the clinical diagnosis of metastatic pheochromocytoma.
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BACKGROUND: The prognostic significance of tumor-infiltrating immune cells in endometrial cancer is a subject of ongoing debate. Recent evidence increasingly suggests that these immune cells and cytokines, abundant in endometrial cancer tissues, play a pivotal role in stimulating the body inherent anti-tumor immune responses. METHODS: Leveraging publicly accessible genetic data, we conducted an exhaustive 2-sample Mendelian randomization (MR) study. This study aimed to explore the causal links between 731 immunophenotypes and the risk of endometrial cancer. We thoroughly assessed the robustness, heterogeneity, and potential horizontal pleiotropy of our findings through extensive sensitivity analyses. RESULTS: Our study identified 36 immunophenotypes associated with endometrial cancer risk. Specific immunophenotypes, such as the percentage of Naive-mature B-cells in lymphocytes (ORâ =â 0.917, 95% CIâ =â 0.863-0.974, Pâ =â .005), and HLA DR expression on CD14-CD16â +â monocytes (ORâ =â 0.952, 95% CIâ =â 0.911-0.996, Pâ =â .032), exhibited a negative correlation with endometrial cancer. Conversely, CD127 expression on CD45RAâ +â CD4â +â in Treg cells (ORâ =â 1.042, 95% CIâ =â 1.000-1.085, Pâ =â .049), and CM CD4+%T in T cell maturation stages (ORâ =â 1.074, 95% CIâ =â 1.012-1.140, Pâ =â .018) showed a positive correlation. Reverse MR analysis linked endometrial cancer to 4 immunophenotypes, including a positive correlation with CD127-CD8br %T cell of Treg (ORâ =â 1.172, 95% CIâ =â 1.080-1.270, Pâ =â .0001), and negative correlations with 3 others, including CM CD4+%T cell (ORâ =â 0.905, 95% CIâ =â 0.832-0.984, Pâ =â .019). CONCLUSION SUBSECTIONS: Our findings underscore a significant causal relationship between immunophenotypes and endometrial cancer in bidirectional MR analyses. Notably, the CM CD4+%T immunophenotype emerged as potentially crucial in endometrial cancer development.
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Neoplasias do Endométrio , Análise da Randomização Mendeliana , Feminino , Humanos , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/imunologia , Imunofenotipagem , Linfócitos do Interstício Tumoral/imunologiaRESUMO
Objective To investigate the expression of Yes-associated protein (YAP) in cutaneous squamous cell carcinoma (cSCC) and its effects on invasion and migration. Methods Immunohistochemical staining was used to detect the expression of YAP in cSCC, Bowen disease (BD), and adjacent normal tissues, and analyzed the correlation between YAP expression and clinicopathological characteristics of cSCC. A stable cell line in A431 cells with YAP gene silencing was established through lentiviral infection. Tetramethylrhodamine isothiocyanate (TRITC)-phalloidin staining was performed to analyze the distribution and number of microfilaments in A431 cells. TranswellTM chamber assay was performed to detect the invasion ability of cells, and scratch healing assay was used to determine the migration ability. Immunofluorescence cytochemistry was used to detected the expression of EMT-related markers, including epithelial-cadherin (E-cadherin), zinc-finger transcription factors Snail in A431 cells with YAP silencing. Western blot analysis was employed to detect the expression of E-cadherin, snail, ß-catenin, phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), phosphorylaedAKT (p-AKT), ribosomal proteinS6(S6), phosphorylatedS6 (p-S6), 4E-binding protein 1 (4EBP1), and phosphorylated 4EBP1 (p-4EBP1). ResultsThe expression of YAP was significantly higher in BD and cSCC tissues compared to adjacent tissues. The strong positive rate of YAP in cSCC tissues was associated with tumor size, differentiation and the level of invasion. However, there was no correlation between YAP expression and gender, age, tumor location, morphological type, or nerve and vascular invasion. After silencing the expression of YAP in A431 cells, the migration and invasion ability of tumor cells were significantly reduced, and cell microfilaments became thinner with reduced pseudopodia. The expression of E-cadherin was increased, while the expression of snail, ß-catenin, p-AKT, p-S6 and p-4EBP1were decreased. Conclusion YAP is highly expressed in cSCC tissues, and promotes the cell migration and invasion of cSCC cells by activating the PI3K/AKT signaling pathway and EMT.
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Carcinoma de Células Escamosas , Neoplasias Cutâneas , Humanos , Fosfatidilinositol 3-Quinase , Carcinoma de Células Escamosas/genética , Proteínas Proto-Oncogênicas c-akt , beta Catenina , Fosfatidilinositol 3-Quinases , Proteínas de Sinalização YAP , Neoplasias Cutâneas/genética , CaderinasRESUMO
Neuronopathy, distal hereditary motor, type VIII is an exceedingly rare autosomal dominant genetic disorder, also known as congenital non-progressive distal spinal muscular atrophy. It is characterized by progressive weakness in distal motor function and atrophy of muscles, without accompanying sensory impairment. Presently, there is limited literature on this condition, and accurate epidemiological data regarding its incidence remains unavailable. We report a paediatric case of distal hereditary motor, type VIII that is caused by a heterozygous missense mutation in the TRPV4 gene (NM_021625): c.805C>T. The proband is a 7-year-old male child. During pregnancy, his mother had prenatal ultrasound revealing "inward turning of the feet", a condition persisting after birth. The proband is currently unable to stand independently, exhibiting bilateral clubfoot deformity. Although possessing normal cognitive function, he cannot walk unaided. Computed radiography findings reveal pelvic tilt, bilateral knee joint valgus, and bilateral clubfoot. The patient underwent familial exome sequencing, revealing a mutation in the TRPV4 gene (NM_021625): c.805C>T (p.Arg269Cys). Considering the patient's medical history, clinical manifestations, imaging studies, and genetic test results, the diagnosis for this individual is Neuronopathy, distal hereditary motor, type VIII. This report documents a case involving the TRPV4 gene mutation associated with Neuronopathy, distal hereditary motor, type VIII, contributing valuable case reference for the early diagnosis of this condition.
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Reducing plant height (PH) is one of the core contents of the "Green Revolution", which began in the 1960s in wheat. A number of 27 reduced-height (Rht) genes have been identified and a great number of quantitative trait loci (QTLs) for PH have been mapped on all 21 chromosomes. Nonetheless, only several genes regulated PH have been cloned. In this study, we found the interval of QTL QPh-1B included an EST-SSR marker swes1079. According to the sequence of swes1079, we cloned the TaOSCA1.4 gene. We developed a CAPS marker to analyze the variation across a natural population. The result showed that the PH was significantly different between the two haplotypes of TaOSCA1.4-1B under most of the 12 environments and the average values of irrigation and rainfed conditions. This result further demonstrated that TaOSCA1.4 was associated with PH. Then, we validated the TaOSCA1.4 via RNAi technology. The average PHs of the wild-type (WT), RNAi lines 1 (Ri-1) and 2 (Ri-2) were 94.6, 83.6 and 79.2 cm, respectively, with significant differences between the WT and Ri-1 and Ri-2. This result indicated that the TaOSCA1.4 gene controls PH. TaOSCA1.4 is a constitutively expressed gene and its protein localizes to the cell membrane. TaOSCA1.4 gene is a member of the OSCA gene family, which regulates intracellular Ca2+ concentration. We hypothesized that knock down mutants of TaOSCA1.4 gene reduced regulatory ability of Ca2+, thus reducing the PH. Furthermore, the cell lengths of the knock down mutants are not significantly different than that of WT. We speculate that TaOSCA1.4 gene is not directly associated with gibberellin (GA), which should be a novel mechanism for a wheat Rht gene.
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We aimed to determine the characteristic adverse events (AEs) of iodinated contrast media (IOCM) and to compare the safety profiles of different IOCM. This study used the database of AEs reports submitted by healthcare professionals from 15 Regional Pharmacovigilance Centers between June 24, 2009 and December 31, 2010 in Korea. All reports of IOCM, including iopromide, iohexol, iopamidol, iomeprol, ioversol, iobitridol and iodixanol, were analyzed. Safety profiles were compared between different IOCM at the system organ level using the proportional reporting ratio (PRR) and 95% confidence interval (95% CI). Among a total of 48,261 reports, 6,524 (13.5%) reports were related to the use of IOCM. Iopromide (45.5%), iohexol (16.9%), iopamidol (14.3%) and iomeprol (10.3%) were identified as frequently reported media. 'Platelet, bleeding & clotting disorders' (PRR, 29.6; 95%CI, 1.9-472.6) and 'urinary system disorders' (PRR, 22.3; 95% CI, 17.1-29.1) were more frequently reported for iodixanol than the other IOCM. In conclusion, the frequency of AEs by organ class was significantly different between individual media. These differences among different IOCM should be considered when selecting a medium among various IOCM and when monitoring patients during and after its use to ensure optimum usage and patient safety.
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Meios de Contraste/efeitos adversos , Compostos Radiofarmacêuticos/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos Plaquetários/induzido quimicamente , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Humanos , Lactente , Recém-Nascido , Radioisótopos do Iodo/química , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico por imagem , Cintilografia , Doenças Urológicas/induzido quimicamente , Adulto JovemRESUMO
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects about 2% of children. Due to the shortage of clinicians, there is an urgent demand for a convenient and effective tool based on regular videos to assess the symptom. Computer-aided technologies have become widely used in clinical diagnosis, simplifying the diagnosis process while saving time and standardizing the procedure. In this study, we proposed a computer vision-based motion trajectory detection approach assisted with machine learning techniques, facilitating an objective and effective way to extract participants' movement features (MFs) to identify and evaluate children's activity levels that correspond to clinicians' professional ratings. The designed technique includes two key parts: (1) Extracting MFs of participants' different body key points in various activities segmented from autism diagnostic observation schedule (ADOS) videos, and (2) Identifying the most relevant MFs through established correlations with existing data sets of participants' activity level scores evaluated by clinicians. The research investigated two types of MFs, i.e., pixel distance (PD) and instantaneous pixel velocity (IPV), three participants' body key points, i.e., neck, right wrist, and middle hip, and five activities, including Table-play, Birthday-party, Joint-attention, Balloon-play, and Bubble-play segmented from ADOS videos. Among different combinations, the high correlations with the activity level scores evaluated by the clinicians (greater than 0.6 with p < 0.001) were found in Table-play activity for both the PD-based MFs of all three studied key points and the IPV-based MFs of the right wrist key point. These MFs were identified as the most relevant ones that could be utilized as an auxiliary means for automating the evaluation of activity levels in the ASD assessment.
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Transtorno do Espectro Autista , Transtorno Autístico , Criança , Humanos , Movimento , Movimento (Física) , AeronavesRESUMO
Background: Invasive prenatal evaluation by chromosomal microarray analysis (CMA) and karyotyping might represent an important option in pregnant women, but limited reports have applied CMA and karyotyping of fetuses conceived by assisted reproductive technology (ART). This study aimed to examine the value of CMA and karyotyping in prenatal diagnosis after ART. Methods: This retrospective study included all singleton fetuses conceived by ART from January 2015 to December 2021. Anomalies prenatally diagnosed based on karyotyping and CMA were analyzed. Prevalence rates for various CMA and karyotyping results were stratified based on specific testing indications including isolated-and non-isolated ART groups. The rates of CMA findings with clinical significance (pathogenic/likely pathogenic) and karyotype anomalies were assessed and compared to those of local control individuals with naturally conceived pregnancies and without medical indications. Results: In total, 224 subjects were assessed by karyotyping and CMA. In the examined patients, chromosomal and karyotype abnormality rates were 3.57% (8/224) and 8.93% (20/224), respectively. This finding indicated a 5.35% (12/224)-incremental rate of abnormal CMA was obtained over karyotype analysis (p = 0.019). The risk of CMA with pathogenic findings for all pregnancies conceived by ART (5.80%, 13/224) was markedly elevated in comparison with the background value obtained in control individuals (1.47%, 9/612; p = 0.001). In addition, risk of CMA with clinically pathogenic results in isolated ART groups was significant higher compared to the background risk reported in the control cohort (p = 0.037). Conclusions: Prenatal diagnosis including karyotyping and CMA is recommended for fetuses conceived by ART, with or without ultrasound findings.
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Feto , Diagnóstico Pré-Natal , Gravidez , Feminino , Humanos , Estudos Retrospectivos , Diagnóstico Pré-Natal/métodos , Cariotipagem , Análise em Microsséries/métodos , Feto/anormalidades , CariótipoRESUMO
Interleukin-33 (IL-33) is a member of the IL-1 cytokine family and is believed to play important roles in different diseases by binding to its specific receptor suppression of tumorigenicity 2 (ST2). In the heart, IL-33 is expressed in different cells including cardiomyocytes, fibroblasts, endothelium, and epithelium. Although many studies have been devoted to investigating the effects of IL-33 on heart diseases, its roles in myocardial injuries remain obscure, and thus further studies are mandatory to unravel the underlying molecular mechanisms. We highlighted the current knowledge of the molecular and cellular characteristics of IL-33 and then summarized its major roles in different myocardial injuries, mainly focusing on infection, heart transplantation, coronary atherosclerosis, myocardial infarction, and diabetic cardiomyopathy. This narrative review will summarize current understanding and insights regarding the implications of IL-33 in cardiac diseases and its diagnostic and therapeutic potential for cardiac disease management.
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Interleucina-33 , Infarto do Miocárdio , Humanos , Interleucina-33/metabolismo , Proteína 1 Semelhante a Receptor de Interleucina-1 , Miócitos Cardíacos/metabolismo , Infarto do Miocárdio/patologia , Citocinas/metabolismoRESUMO
Iron is an essential trace element that is involved in a variety of physiological processes. Ferritinophagy is selective autophagy mediated by nuclear receptor coactivator 4 (NCOA4), which regulates iron homeostasis in the body. Upon iron depletion or starvation, ferritinophagy is activated, releasing large amounts of Fe2+ and increasing reactive oxygen species (ROS), leading to ferroptosis. This plays a significant role in the etiopathogenesis of many diseases, such as metabolic diseases, neurodegenerative diseases, infectious diseases, tumors, cardiomyopathy, and ischemia-reperfusion ischemia-reperfusion injury. Here, we first review the regulation and functions of ferritinophagy and then describe its involvement in different diseases, with hopes of providing new understanding and insights into iron metabolism and iron disorder-related diseases and the therapeutic opportunity for targeting ferritinophagy.
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Ferritinas , Neoplasias , Humanos , Ferritinas/metabolismo , Coativadores de Receptor Nuclear/metabolismo , Autofagia , Ferro/metabolismo , Fatores de Transcrição/metabolismoRESUMO
In the pathogenesis of age-related macular degeneration, long non-coding RNAs have become important regulators. This study aimed to investigate the role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in the progression of choroidal neovascularization (CNV) and the underlying mechanisms. The in vivo and in vitro model of CNV was established using laser-induced mouse CNV model and human choroidal vascular endothelial cells (HCVECs) exposed to hypoxia respectively. We explore the role of MALAT1 in the pathogenesis of CNV by using the small interference RNA both in vivo and in vitro. MALAT1 expression was found to be upregulated in the retinal pigment epithelial-choroidal complexes. MALAT1 knockdown inhibited CNV development and leakage in vivo and decreased HCVECs proliferation, migration, and tube formation in vitro. MALAT1 performed the task as a miR-17-5p sponge to regulate the expression of vascular endothelial growth factor A (VEGFA) and E26 transformation specific-1 (ETS1). This study provides a new perspective on the pathogenesis of CNV and suggests that the axis MALAT/miR-17-5p/VEGFA or ETS1 may be an effective therapeutic target for CNV.
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SCO6993 (606 amino acids) in Streptomyces coelicolor belongs to the large ATP-binding regulators of the LuxR family regulators having one DNA-binding motif. Our previous findings predicted that SCO6993 may suppress the production of pigmented antibiotics, actinorhodin, and undecylprodigiosin, in S. coelicolor, resulting in the characterization of its properties at the molecular level. SCO6993-disruptant, S. coelicolor ΔSCO6993 produced excess pigments in R2YE plates as early as the third day of culture and showed 9.0-fold and 1.8-fold increased production of actinorhodin and undecylprodigiosin in R2YE broth, respectively, compared with that by the wild strain and S. coelicolor ΔSCO6993/SCO6993+. Real-time polymerase chain reaction analysis showed that the transcription of actA and actII-ORF4 in the actinorhodin biosynthetic gene cluster and that of redD and redQ in the undecylprodigiosin biosynthetic gene cluster were significantly increased by SCO6993-disruptant. Electrophoretic mobility shift assay and DNase footprinting analysis confirmed that SCO6993 protein could bind only to the promoters of pathway-specific transcriptional activator genes, actII-ORF4 and redD, and a specific palindromic sequence is essential for SCO6993 binding. Moreover, SCO6993 bound to two palindromic sequences on its promoter region. These results indicate that SCO6993 suppresses the expression of other biosynthetic genes in the cluster by repressing the transcription of actII-ORF4 and redD and consequently negatively regulating antibiotic production.
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Streptomyces coelicolor , Trifosfato de Adenosina/metabolismo , Aminoácidos/metabolismo , Antraquinonas/metabolismo , Antibacterianos/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , DNA , Desoxirribonucleases/metabolismo , Regulação Bacteriana da Expressão Gênica , Genes Reguladores , Regiões Promotoras Genéticas , Streptomyces coelicolor/genética , Streptomyces coelicolor/metabolismo , Transativadores/genética , Transativadores/metabolismo , Transcrição GênicaRESUMO
In wheat, a series of dwarf and semi-dwarf plant varieties have been developed and utilized worldwide since the 1960s and caused the 'Green Revolution'. To date, 25 reduced-height (Rht) genes have been identified, but only several genes for plant height (PH) have been isolated previously. In this study, we identified a candidate gene, ATP-dependent DNA helicase (TaDHL-7B), for PH via QTL mapping and genome-wide association study (GWAS) methods. We knocked out this gene using the CRISPR/Cas9 system in variety 'Fielder'. Two homozygous mutant genotypes, AAbbDD (-5 bp) and AAbbDD (-1 bp), were obtained in the T2 generation. The PH values of AAbbDD (-5 bp) and AAbbDD (-1 bp) were significantly reduced compared with the wild-type (WT, 'Fielder'), indicating that TaDHL-7B is a novel Rht gene that controls the PH. This is the first time that a PH gene of wheat has been isolated with a non-hormone pathway, providing a new insight into the genetic control of PH. The TaDHL gene reduced the PH without a yield penalty. It could be used to improve the lodging resistance and yield in wheat breeding programs.
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Melhoramento Vegetal , Triticum , DNA Helicases/genética , Genes de Plantas , Estudo de Associação Genômica Ampla , Triticum/genéticaRESUMO
Streptomyces coelicolor is a filamentous soil bacterium producing several kinds of antibiotics. S. coelicolor abs8752 is an abs (antibiotic synthesis deficient)-type mutation at the absR locus; it is characterized by an incapacity to produce any of the four antibiotics synthesized by its parental strain J1501. A chromosomal DNA fragment from S. coelicolor J1501, capable of complementing the abs- phenotype of the abs8752 mutant, was cloned and analyzed. DNA sequencing revealed that two complete ORFs (SCO6992 and SCO6993) were present in opposite directions in the clone. Introduction of SCO6992 in the mutant strain resulted in a remarkable increase in the production of two pigmented antibiotics, actinorhodin and undecylprodigiosin, in S. coelicolor J1501 and abs8752. However, introduction of SCO6993 did not show any significant difference compared to the control, suggesting that SCO6992 is primarily involved in stimulating the biosynthesis of antibiotics in S. coelicolor. In silico analysis of SCO6992 (359 aa, 39.5 kDa) revealed that sequences homologous to SCO6992 were all annotated as hypothetical proteins. Although a metalloprotease domain with a conserved metal-binding motif was found in SCO6992, the recombinant rSCO6992 did not show any protease activity. Instead, it showed very strong ß-glucuronidase activity in an API ZYM assay and toward two artificial substrates, p-nitrophenyl-ß-D-glucuronide and AS-BI-ß-D-glucuronide. The binding between rSCO6992 and Zn2+ was confirmed by circular dichroism spectroscopy. We report for the first time that SCO6992 is a novel protein with ß-glucuronidase activity, that has a distinct primary structure and physiological role from those of previously reported ß-glucuronidases.
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Antibacterianos/biossíntese , Proteínas de Bactérias/genética , Glucuronidase/genética , Streptomyces coelicolor/genética , Sequência de Aminoácidos , Antraquinonas/metabolismo , Proteínas de Bactérias/metabolismo , Dosagem de Genes , Regulação Bacteriana da Expressão Gênica , Teste de Complementação Genética , Glucuronidase/metabolismo , Mutação , Prodigiosina/análogos & derivados , Prodigiosina/biossíntese , Alinhamento de Sequência , Streptomyces coelicolor/enzimologiaRESUMO
BACKGROUND: Primary chondrosarcoma of the liver are extremely rare. Moreover, there are few reports focusing on typical clinical symptoms and imaging characteristics. Therefore, the diagnosis of chondrosarcoma of the liver remains a challenge. CASE SUMMARY: A 59-year-old male was admitted due to a lesion occupying the right liver lobe that was found by physical examination. Magnetic resonance imaging showed a lobular mass with high T2 weighted image and low T1 weighted image with enhanced internal separation and edge in the right liver. He was diagnosed with liver cystadenoma by using magnetic resonance imaging. At 3 mo later, the magnetic resonance scan showed that the mass was enlarged. Laparoscopic liver tumor resection was performed with a pathological diagnosis of liver chondrosarcoma. Then he received a surgical resection for the recurrent lesion. However, intrahepatic and abdominal metastases were found again at 8 mo after the second operation. The patient then received conservative management and is now under follow-up. CONCLUSION: Primary liver chondrosarcoma generally is presented as lobulated and heterogeneous density/signal, cystic, solid masses without calcification with enhanced edge, internal septa and solid part. The imaging features are closely related to pathology, which may be helpful for clinical diagnosis.
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Previous studies have suggested that the loss of the translation initiation factor eIF4G1 homolog NAT1 induces excessive self-renewability of naive pluripotent stem cells (PSCs); yet the role of NAT1 in the self-renewal and differentiation of primed PSCs is still unclear. Here, we generate a conditional knockout of NAT1 in primed PSCs and use the cells for the functional analyses of NAT1. Our results show that NAT1 is required for the self-renewal and neural differentiation of primed PSCs. In contrast, NAT1 deficiency in naive pluripotency attenuates the differentiation to all cell types. We also find that NAT1 is involved in efficient protein expression of an RNA uridyltransferase, TUT7. TUT7 is involved in the neural differentiation of primed PSCs via the regulation of human endogenous retrovirus accumulation. These data demonstrate the essential roles of NAT1 and TUT7 in the precise transition of stem cell fate.
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Diferenciação Celular , Retrovirus Endógenos/metabolismo , Neurônios/citologia , Células-Tronco Pluripotentes/citologia , RNA Viral/metabolismo , Animais , Arilamina N-Acetiltransferase/deficiência , Arilamina N-Acetiltransferase/genética , Arilamina N-Acetiltransferase/metabolismo , Linhagem Celular , Linhagem da Célula , Autorrenovação Celular , Retrovirus Endógenos/genética , Edição de Genes , Humanos , Isoenzimas/deficiência , Isoenzimas/genética , Isoenzimas/metabolismo , Camundongos , Neurônios/metabolismo , Iniciação Traducional da Cadeia Peptídica , Células-Tronco Pluripotentes/metabolismo , Interferência de RNA , RNA Nucleotidiltransferases/genética , RNA Nucleotidiltransferases/metabolismo , RNA Interferente Pequeno/metabolismo , RNA Viral/antagonistas & inibidores , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
In two growing seasons of wheat (2015-2017), we conducted a field trial with Taishan 28 in Tai'an Academy of Agricultural Science Feicheng experimental base, Tai'an City, Shandong Province. There were four irrigation levels of 150 (A1), 300 (A2), 450 (A3), and 600 (A4) m3·hm-2, and four nitrogen application levels of 90 (B1), 135 (B2), 180 (B3), and 225 (B4) kg·hm-2. We examined the effects of the combination effects of irrigation and nitrogen on dry matter accumulation and transport, nitrogen accumulation and transport, water consumption and utilization, photosynthetic characteristics, wheat grain yield and yield components of wheat. The results showed that dry matter accumulation, nitrogen accumulation, vegetative organs production, storage and the transportation volume to grains of the dry matter and nitrogen, and dry matter and nitrogen accumulation of grain in the mature stage of wheat all reached the maximum in A3B3 treatment, which were significantly different from other treatments. Under all the nitrogen treatments, soil water consumption in the 60-200 cm soil layer was A3>A4>A2>A1. Water use efficiency and nitrogen use efficiency in A3B3 treatment were higher than that under A3B4, A4B3 and A4B4. The net photosynthetic rate, stomatal conductance and transpiration rate of flag leaves from 7 to 28 days after flowe-ring were all significantly higher in A3B3 treatment, which was conducive to the photosynthetic synthesis of carbohydrates in wheat. The interaction effect of water and nitrogen addition significantly affected grain yield and yield components. Wheat yield was the highest in A3B3 treatment which reached at 9400 kg·hm-2. In conclusion, the treatment with irrigation of 450 m3·hm-2 and nitrogen of 180 kg·hm-2 could significantly improve dry matter and nitrogen accumulation, and promote transportation volume of the dry matter and nitrogen to grain. Compared with the high water and nitrogen treatment, it could effectively increase water use efficiency and nitrogen use efficiency, enhance photosynthetic capacity of flag leaf, produce more carbohydrate, and increase grain yield.
Assuntos
Nitrogênio , Triticum , Irrigação Agrícola , Biomassa , Fertilizantes , Estações do Ano , ÁguaRESUMO
AIM: To investigate the association between variables related to tea consumption (duration, frequency, and type) and the risk of diabetic retinopathy. METHODS: A rural community-based, cross-sectional survey was conducted in Weitang Town, Suzhou, China. People aged 60 years or above were invited to complete the survey. All eligible patients underwent detailed eye examination. Diabetic retinopathy (DR) was diagnosed and graded based on the retinal fundus imaging. Diabetes was defined as fasting glucose concentrations of ≥7.0 mmol/L or self-reported diagnosis of diabetes. Information about tea consumption such as duration, type, and frequency, together with demographics and lifestyle characteristics, were collected using a face-to-face questionnaire interview. The association between tea consumption and the risk of DR was determined by univariate and multivariate logistic regression analyses. RESULTS: Among the 5,281 participants, 614 had diabetes mellitus (prevalence of 11.63%). The prevalence rate of DR was 10.38% in the diabetic population and 1.04% in the general population. Compared with non-tea consumers, the crude OR values for DR in subjects with long-term and short-term tea consumption were 0.34 (95%CI = 0.14-0.82, p = 0.016) and 1.64 (95%CI = 0.74-3.64, p = 0.221), respectively. When adjusted for age, gender, and other confounders, consumption of tea for ≥20 years was associated with reduced odds of DR (OR = 0.29, 95%CI = 0.09-0.97, p = 0.044). Thus, long-term tea consumption was significantly associated with a lower risk of DR. There was no statistical significance between frequency or type of tea consumption with DR (p > 0.05). CONCLUSION: Elderly diabetic Chinese residents who consumed tea for more than twenty years had a lower risk of DR compared to non-tea consumers. The long-term tea consumption may be an independent protective factor for DR. However, further studies are warranted to examine the association.