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Phylogenetic methods are widely used to reconstruct the evolutionary relationships among species and individuals. However, recombination can obscure ancestral relationships as individuals may inherit different regions of their genome from different ancestors. It is, therefore, often necessary to detect recombination events, locate recombination breakpoints, and select recombination-free alignments prior to reconstructing phylogenetic trees. While many earlier studies have examined the power of different methods to detect recombination, very few have examined the ability of these methods to accurately locate recombination breakpoints. In this study, we simulated genome sequences based on ancestral recombination graphs and explored the accuracy of three popular recombination detection methods: MaxChi, 3SEQ, and Genetic Algorithm Recombination Detection. The accuracy of inferred breakpoint locations was evaluated along with the key factors contributing to variation in accuracy across datasets. While many different genomic features contribute to the variation in performance across methods, the number of informative sites consistent with the pattern of inheritance between parent and recombinant child sequences always has the greatest contribution to accuracy. While partitioning sequence alignments based on identified recombination breakpoints can greatly decrease phylogenetic error, the quality of phylogenetic reconstructions depends very little on how breakpoints are chosen to partition the alignment. Our work sheds light on how different features of recombinant genomes affect the performance of recombination detection methods and suggests best practices for reconstructing phylogenies based on recombination-free alignments.
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Algoritmos , Filogenia , Recombinação Genética , Pontos de Quebra do Cromossomo , Alinhamento de Sequência/métodos , Modelos GenéticosRESUMO
OBJECTIVE: Olecranon osteotomy and paratricipital approaches were widely used in the treatment of type C distal humerus fracture but some disadvantages exist, so a combined medial and lateral approach was designed. The objective of this study was to investigate and compare the clinical outcomes of combined medial and lateral approach with the paratricipital approach in open reduction and internal fixation of type C distal humerus fractures. METHODS: From May 2018 to April 2020, 37 patients with type C distal humerus fracture who accepted open reduction and internal fixation in our hospital were enrolled in this study. All cases were randomly divided into two groups according to the surgical approach: combined medial and lateral approach group (19 cases), paratricipital approach group (18 cases). All of the patients received open reduction and double vertical plates fixation. The operation and follow-up indexes, including operation time, blood loss, incision length, triceps muscle strength, flexion-extension arc of elbow and forearm rotation arc, were recorded and compared. Caja score was used to assess the quality of fractures reduction. Mayo Elbow Performance Score (MEPS) was used to evaluate the elbow function in the follow-up. Complications such as incision infection, ulnar nerve injury, degenerative osteoarthritis, and heterotopic ossification were analyzed. RESULTS: The differences in age, gender, and AO classification of fractures between two groups were not statistically significant (p > 0.05). The sum of medial and lateral incision length of combined approach group was longer than the midline incision of paratricipital approach group (15.4 ± 0.8 vs. 14.6 ± 0.8, p < 0.05), but there was no significant difference in operation time (103.5 ± 10.2 vs. 106.0 ± 8.8, p > 0.05), blood loss (71.3 ± 24.5 vs. 72.8 ± 24.6, p > 0.05), and Caja score (16.05 ± 5.67 vs. 15.56 ± 5.66, p > 0.05). During the follow-up, the MEPS of combined approach group was higher than that of paratricipital approach group at 3 months postoperatively (80.5 ± 5.7 vs. 68.9 ± 8.1, p < 0.05), but there was no significant difference in MEPS at 6 months postoperatively (83.9 ± 6.6 vs. 79.7 ± 7.0, p > 0.05) and at the last follow-up (86.8 ± 7.1 vs. 86.9 ± 7.7, p > 0.05) between the two groups. There was no significant difference in triceps muscle strength (p > 0.05), flexion-extension arc (126.8 ± 5.3 vs. 128.9 ± 6.0, p > 0.05), and forearm rotation arc (163.2 ± 5.3 vs. 163.6 ± 4.8, p > 0.05) at the last follow-up. Although the incidence of complication of combined approach group (15.8%) was lower than that of paratricipital approach group (22.2%), the difference was not statistically significant (p > 0.05). CONCLUSIONS: The combined medial and lateral approach was an effective and safe way of open reduction and internal fixation for type C distal humerus fractures. Compared with the paratricipital approach, the combined medial and lateral approach could restore the elbow function more quickly postoperatively, and the long-term results were comparable.
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Articulação do Cotovelo , Fraturas Distais do Úmero , Fraturas do Úmero , Olécrano , Humanos , Fraturas do Úmero/cirurgia , Resultado do Tratamento , Olécrano/cirurgia , Articulação do Cotovelo/cirurgia , Fixação Interna de Fraturas/métodos , Amplitude de Movimento Articular/fisiologia , Úmero/cirurgia , Estudos RetrospectivosRESUMO
Developing a highly sensitive immunoassay for tumor biomarkers is particularly important in bioanalysis and early disease diagnosis. In this work, a simple one-pot solvothermal method was developed for controllable synthesis of well-dispersed PtCo alloyed nanodendrites (PtCo NDs) by using l-carnosine as the co-structure-directing agent. The PtCo NDs had a large specific surface area and provided abundant active sites available for electrocatalytic oxygen reduction reaction (ORR). Based on the highly enhanced currents of the ORR, a novel label-free electrochemical immunosensor was fabricated for highly sensitive assay of carbohydrate antigen 15-3 (CA15-3). The sensor showed a wide linear range of 0.1-200 U mL-1 and a low limit of detection (LOD) down to 0.0114 U mL-1 (S/N = 3), in turn exploring its application to diluted human serum samples with satisfactory results. This study provides a feasible platform for monitoring other tumor markers in clinical diagnosis.
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Técnicas Biossensoriais , Nanopartículas Metálicas , Anticorpos Imobilizados , Carboidratos , Catálise , Técnicas Eletroquímicas , Ouro , Humanos , Imunoensaio , Limite de Detecção , OxigênioRESUMO
OBJECTIVE: To investigate the factors, surgical treatment methods and clinical effect of internal fixation failure of intertrochanteric and subtrochanteric fractures. METHODS: From June 2015 to May 2019, arthroplasty and internal fixation revision were used to treat 18 cases of internal fixation failure of intertrochanteric and subtrochanteric fractures. There were 10 males and eight females, with an average age of 67.3 years (38-92 years). The 16 cases of initial intertrochanteric fractures were classified according to AO/OTA:13 cases of A2 and 3 cases of A3, the other 2 cases were subtrochanteric fractures (Seinsheimer type IV). The internal fixation failure was treated with total hip arthroplasty (6 cases), bipolar hemiarthroplasty (4 cases), revision with proximal femoral lockingplate (4 cases) and extend intramedullary nail (4 cases). RESULTS: All patients were followed up for an average of 24.7 months (range, 12 to 36 months). The average operative time was 111.4 min (range, 72 to 146 min) and the average intraoperative blood loss was 403.6 mL (range, 200 to 650 mL). The average time of fracture union was 6.9 months (range, 5 to 9 months) for cases of internal fixation revision. The operative time of the arthroplasty group was shorter than the revision group (P < 0.001), and the intraoperative blood loss of the arthroplasty group was less than the revision group (P = 0.001). The affected limb shortening of postoperative (0.21 ± 0.19 cm) was better than preoperative (2.01 ± 0.60 cm) (P < 0.001), while the limb shortening of the arthroplasty group (0.11 ± 0.21 cm) was less than the revision group (0.33 ± 0.09 cm) (P = 0.015). At the last follow-up, all injured limbs regained walking function, and the Harris hip score was 81.3 ± 9.4 points. The Harris score of postoperative was better than preoperative (33.4 ± 5.9 points) (P < 0.001), while there were no significant differences between the arthroplasty group and the revision group at 3 months (76.5 ± 8.5 vs 71.1 ± 10.6, P = 0.249), 6 months (80.9 ± 7.9 vs 78.9 ± 12.9,P = 0.687) postoperative and the last follow-up (80.5 ± 8.3 vs 82.3 ± 11.7, P = 0.716) respectively. CONCLUSION: For internal fixation failure of peritrochanteric fractures, young patients could accept internal fixation revision to restore normal anatomical structure, correct varus deformity and autograft; while elderly patients and patients with damaged femoral head could be treated with arthroplasty to restore walking function.
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Artroplastia de Quadril/métodos , Fixação Interna de Fraturas/métodos , Fraturas do Quadril/cirurgia , Complicações Pós-Operatórias/cirurgia , Reoperação/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Inquéritos e QuestionáriosRESUMO
Objective:To explore the value of different machine learning models based on Gd-EOB-DTPA enhanced MRI hepatobiliary phase radiomics features in preoperative prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC).Methods:The data of 132 patients with HCC confirmed by pathology in the First Affiliated Hospital of Soochow University from January 2015 to May 2020 were retrospectively analyzed, including 72 cases of positive MVI and 60 cases of negative MVI. According to the proportion of 7∶3, the cases were randomly divided into training set and validation set. The radiomics features of hepatobiliary phase images for HCC were extracted by PyRadiomics software. The clinical and radiomics features of the training set were screened by the least absolute shrinkage and selection operator (LASSO) regression with 5 fold cross-validation, and then the optimal feature subset was obtained. Six machine learning algorithms, including decision tree, extreme gradient boosting, random forest, support vector machine (SVM), generalized linear model (GLM) and neural network, were used to build the prediction models, and the ROC curves were used to evaluate the prediction ability of the models. DeLong test was used to compare the differences of area under the curve (AUC) for 6 machine learning algorithms.Results:Totally 14 features selected by LASSO regression were obtained to form the optimal feature subset, including 2 clinical features (maximum tumor diameter and alpha-fetoprotein) and 12 radiomics features. The AUCs of decision tree, extreme gradient boosting, random forest, SVM, GLM and neural network based on the optimal feature subset were 0.969, 1.000, 1.000, 0.991, 0.966, 1.000 in the training set and 0.781, 0.890, 0.920, 0.806, 0.684, 0.703 in the validation set, respectively. There were significant differences in the AUCs between extreme gradient boosting and GLM or neural network ( Z=2.857, 3.220, P=0.004, 0.001). The differences in AUCs between random forest and SVM, GLM, or neural network were significant ( Z=2.371, 3.190, 3.967, P=0.018, 0.001,<0.001). The difference in AUCs between SVM and GLM was statistically significant ( Z=2.621 , P=0.009). There were no significant differences in the AUCs among the other machine learning models ( P>0.05). Conclusion:Machine learning models based on Gd-EOB-DTPA enhanced MRI hepatobiliary phase radiomics features can be used to preoperatively predict MVI of HCC, particularly the extreme gradient boosting and random forest models have high prediction efficiency.
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The gut microbiota has been identified as a target of toxic metals and a potentially crucial mediator of the bioavailability and toxicity of these metals. In this study, we show that aluminum (Al) exposure, even at low dose, affected the growth of representative strains from the human intestine via pure culture experiments. In vitro, Lactobacillus plantarum CCFM639 could bind Al on its cell surface as shown by electron microscopy and energy dispersive X-ray analysis. The potential of L. plantarum CCFM639 to reverse changes in human intestine microbiota induced by low-dose dietary Al exposure was investigated using an in vitro colonic fermentation model. Batch fermenters were inoculated with fresh stool samples from healthy adult donors and supplemented with 86 mg/L Al and/or 109 CFU of L. plantarum CCFM639. Al exposure significantly increased the relative abundances of Bacteroidetes (Prevotella), Proteobacteria (Escherichia), Actinobacteria (Collinsella), Euryarchaeota (Methanobrevibacter), and Verrucomicrobiaceae and decreased Firmicutes (Streptococcus, Roseburia, Ruminococcus, Dialister, Coprobacillus). Some changes were reversed by the inclusion of L. plantarum CCFM639. Alterations in gut microbiota induced by Al and L. plantarum CCFM639 inevitably led to changes in metabolite levels. The short-chain fatty acid (SCFAs) contents were reduced after Al exposure, but L. plantarum CCFM639 could elevate their levels. SCFAs had positive correlations with beneficial bacteria, such as Dialister, Streptococcus, Roseburia, and negative correlations with Erwinia, Escherichia, and Serratia. Therefore, dietary Al exposure altered the composition and structure of the human gut microbiota, and this was partially mitigated by L. plantarum CCFM639. This probiotic supplementation is potentially a promising and safe approach to alleviate the harmful effects of dietary Al exposure.
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Alumínio , Microbioma Gastrointestinal , Lactobacillus plantarum , Alumínio/toxicidade , Dieta , Fermentação , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Técnicas In VitroRESUMO
BACKGROUND: Optic atrophy 1 (OPA1) gene mutations are associated with dominantly inherited optic neuropathy resulting in a progressive loss of visual acuity. Compound heterozygous or homozygous variants that lead to severe phenotypes, including Behr syndrome, have been reported rarely. CASE PRESENTATION: Here, we present a 14-month-old boy with early onset optic atrophy, congenital cataracts, neuromuscular disorders, mental retardation, and developmental delay. Combined genetic testing, including whole exome sequencing (WES) and chromosomal microarray analysis, revealed a concurrent OPA1 variant (c.2189 T > C p.Leu730Ser) and de novo chromosome 3q deletion as pathogenic variants leading to the severe phenotype. CONCLUSIONS: Our case is the first reporting a novel missense OPA1 variant co-occurring with a chromosomal microdeletion leading to a severe phenotype reminiscent of Behr syndrome. This expands the mutation spectrum of OPA1 and inheritance patterns of this disease.
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Deficiência Intelectual , Atrofia Óptica , Ataxia , Cromossomos , GTP Fosfo-Hidrolases/genética , Perda Auditiva , Humanos , Lactente , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Masculino , Mutação , Atrofia Óptica/congênito , Atrofia Óptica/genética , Linhagem , EspasmoRESUMO
Direct ethylene glycol fuel cells (DEGFCs) and water splitting devices have received intensive interest during the past few decades. However, the commonly used Pt catalysts are seriously restricted by the high cost and very low resistance to CO-like intermediates during the catalysis. Herein, a general and simple solvothermal method was developed to synthesize three-dimensional (3D) bimetallic alloyed PtRh nanodendrites (NDs) for ethylene glycol oxidation reaction (EGOR) and hydrogen evolution reaction (HER). Citric acid (CA) and cetyltrimethylammonium chloride (CTAC) played important roles in formation of such dendritic structures. The optimized Pt56Rh44 NDs displayed the greatest mass activity (MA) for EGOR in 0.5 M KOH, which was 2.6-fold higher than commercial Pt black, coupled with the remarkable increase in the HER activity with a decayed overpotential of 20.0 mV to drive a current density of 10 mA cm-2 relative to the homemade Pt41Rh59 NDs (26.2 mV), Pt81Rh19 NDs (26.2 mV), Pt black (44.3 mV), Pt/C (44.4 mV) and Rh NFs (37.3 mV). This work offers some constructive guidelines for synthesis of advanced Pt-based catalysts in such energy devices.
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Lactobacillus salivarius is a species of lactic acid bacteria with probiotic potency. Compared to such well-known probiotics as L. rhamnosus and L. casei, the genomic characteristics and health-beneficial effects of L. salivarius are inadequately researched. For this study, a medium with enhanced selectivity for the isolation of L. salivarius was developed by optimizing the carbon source and antibiotics in the medium. Seventy-three L. salivarius strains were isolated from 472 fecal samples from Chinese populations, and their pan-genomic and phylogenetic characterizations were analyzed. Three strains (L. salivarius HN26-4, NT4-8, and FXJCJ7-2) that were clearly categorized in different sub-phylotypes of the phylogenetic tree were randomly selected for further studies. Compared to the other two tested strains, L. salivarius FXJCJ7-2 showed higher tolerance to simulated gastrointestinal tract conditions and more significant anti-inflammatory effects in lipopolysaccharides (LPS)-treated RAW264.7 murine macrophages. This strain was also more effective in reversing LPS-induced alterations in gut barrier function, colonic histopathology, Treg/Th-17 balance, immunomodulatory indicators, nuclear factor kappa B pathway activation, and the intestinal microenvironment of the mice than the other two tested strains. Comparative genomic analysis indicated that these protective effects may be related to the specific genes of L. salivarius FXJCJ7-2 that were involved in the tolerance to the gastrointestinal environment, short-chain fatty acid production, and host-bacterium interaction.
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Fezes/microbiologia , Trato Gastrointestinal/microbiologia , Inflamação/metabolismo , Ligilactobacillus salivarius/isolamento & purificação , Animais , China , Humanos , Ligilactobacillus salivarius/classificação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células RAW 264.7 , Linfócitos T Reguladores/citologia , Células Th17/citologiaRESUMO
Insomnia is a common health problem in modern societies. GABA, an inhibitory neurotransmitter, can promote relaxation and reduce anxiety. In this study, milk was fermented with Lactobacillus brevis DL1-11, a strain with high GABA-producing capacity. The potential beneficial effects of this fermented milk on anxiety and sleep quality were evaluated in animal experiments. Sixty mice were divided into control, non-GABA fermented milk (NGFM), low-dose GABA fermented milk (LGFM, 8.83â¯mg/kg.bw), medium-dose GABA fermented milk (MGFM, 16.67â¯mg/kg.bw), high-dose GABA fermented milk (HGFM, 33.33â¯mg/kg.bw) and diazepam groups. The results of open field test and elevated plus-maze test indicated decreases in anxiety behavior after oral HGFM administration. Moreover, mice in the HGFM group exhibited a significantly prolonged sleep time after an intraperitoneal injection of sodium pentobarbital and a shortened sleep latency after an intraperitoneal injection of sodium barbital. These results indicate a beneficial effect of HGFM on sleep. Additionally, significant increases in the relative abundances of Ruminococcus, Adlercreutzia and Allobaculum and the levels of some short-chain fatty acids (SCFAs), such as butyric acid, were observed in the HGFM group. The results suggest that GABA-fermented milk may improve sleep and the protective pathways may involve in regulation of gut microbiota and increase of SCFAs level.
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Produtos Fermentados do Leite , Microbioma Gastrointestinal , Levilactobacillus brevis , Distúrbios do Início e da Manutenção do Sono/terapia , Ácido gama-Aminobutírico/química , Animais , Ácidos Graxos Voláteis/análise , Masculino , Camundongos , Camundongos Endogâmicos ICRRESUMO
Objective:To explore the value of spectral CT radiomics quantitative features on differentiating lung cancer nodule from inflammatory nodule.Methods:The spectral CT imaging data of 96 lung cancer nodules and 45 inflammatory nodules from the First Affiliated Hospital of Soochow University were analyzed retrospectively. According to a ratio of two to one, patients were randomly assigned to the training group and validation group, including 64 lung cancer nodules and 30 inflammatory nodules in the training group, 32 lung cancer nodules and 15 inflammatory nodules in the validation group. MaZda software was used for radiomic feature extraction from the 70 keV monochromatic images in arterial phase and venous phase for lung cancer nodules and inflammatory nodules in the training group. Fisher coefficients (Fisher), classification error probability combined average correlation coefficients (POE+ACC) and mutual information (MI) were used to select 10 optimal features for the optimal feature subsets. The optimal feature subsets were analyzed by using linear discriminant analysis (LDA) and nonlinear discriminant analysis (NDA) to calculate the area under the receiver operating characteristic (ROC) curve (AUC), accuracy, sensitivity, specificity, precise and F1 score in differentiating lung cancer nodule from inflammatory nodule. The prediction model was established using the optimal feature subsets in the training group with artificial neural network (ANN). Then the established prediction model was used to differentiate lung cancer nodule from inflammatory nodule in the validation group. Delong test was used to compare the differences in the AUC of different optimal feature subsets.Results:In arterial phase, the optimal feature subset obtained from MI-NDA had the highest AUC of 0.888 [95% confidence interval (CI) 0.806-0.943], accuracy rate of 88.3%, sensitivity of 87.5% and specificity of 90.0%, on the differential diagnosis of lung cancer nodule and inflammatory nodule in the training group. There was no significant difference in AUC between MI-NDA and Fisher-NDA or (POE+ACC)-NDA method ( Z=1.941, P=0.052; Z=1.683, P=0.092). In venous phase, the optimal feature subset obtained from (POE+ACC)-NDA had the highest AUC of 0.846 (95%CI 0.757-0.912), accuracy rate of 87.2%, sensitivity of 92.2% and specificity of 76.7%, on the differential diagnosis of lung cancer nodule and inflammatory nodule in the training group. There was no significant difference in AUC between(POE+ACC)-NDA and MI-NDA method ( Z=1.354, P=0.18), but significant difference between (POE+ACC)-NDA and Fisher-NDA method ( Z=2.423, P=0.015). In the validation group and training group, the optimal feature subset selected by MI-NDA method had the highest AUC of 0.888(95%CI 0.806-0.943) and 0.871(95%CI 0.741-0.951). Conclusion:Spectral CT radiomics quantitative features have great value on the differential diagnosis of lung cancer nodule and inflammatory nodule.
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Lactobacillus plantarum, a widely used probiotic in the food industry, exists in diverse habitats, which has led to its niche-specific genetic evolution. However, the relationship between this type of genetic evolution and the bacterial phenotype remains unclear. Here, six L. plantarum strains derived from paocai and human feces were analyzed at the genomic and phenotypic levels to investigate the features of adaptive evolution in different habitats. A comparative genomic analysis showed that 93 metabolism-related genes underwent structural variations (SVs) during adaptive evolution, including genes responsible for carbohydrate, lipid, amino acid, inorganic ion and coenzyme transport and metabolism, and energy production and conversion. Notably, seven virulence factor-related genes in strains from both habitats showed SVs - similar to the pattern found in the orthologous virulence genes of pathogenic bacteria shared similar niches, suggesting the possibility of horizontal gene transfer. These genomic variations further influenced the metabolic abilities of strains and their interactions with the commensal microbiota in the host intestine. Compared with the strains from feces, those from paocai exhibited a shorter stagnation period and a higher growth rate in a diluted paocai solution because of variations in functional genes. In addition, opposite correlations were identified between the relative abundances of L. plantarum strains and the genus Bifidobacterium in two media inoculated with strains from the two habitats. Overall, our findings revealed that the niche-specific genetic evolution of L. plantarum strains is associated with their fermentation abilities and physiological functions in host gut health. This knowledge can help guiding the exploration and application of probiotics from the specific niches-based probiotic exploitation.
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Lactobacillus plantarum , Probióticos , Fezes , Fermentação , Genômica , Humanos , Lactobacillus plantarum/genéticaRESUMO
The heavy metal lead (Pb) is a toxic contaminant that induces a range of adverse effects in humans. The present study demonstrated for the first time that dietary supplementation with a galactooligosaccharide (GOS) promotes fecal Pb excretion and reduces Pb accumulation in the blood and tissues of mice. The effects against Pb exposure were also observed in mice that received the fecal microbiota from donors treated with GOS, but were diminished in gut microbiota-depleted mice that received antibiotic pre-treatment, indicating that the protection by GOS administration was dependent on the modulation of the gut microbiota. We also provide evidence that the protective mechanism of GOS supplementation was related to the enhanced abundance of intestinal bacteria with good Pb-binding ability, recovery of the gut barrier function, modulation of bile acid metabolism, and improved essential metal utilization. These results indicate that GOS can be considered a potentially protective prebiotic against Pb toxicity.
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Microbioma Gastrointestinal/efeitos dos fármacos , Chumbo/metabolismo , Oligossacarídeos/metabolismo , Substâncias Protetoras/metabolismo , Animais , Humanos , Chumbo/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Prebióticos/análiseRESUMO
Autism spectrum disorder (ASD) is a neuro-developmental disorder that is characterized by impairments of reciprocal social interaction and restricted stereotyped repetitive behavior. The goal of the present study was to investigate the trace element and gut microbiota profiles of Chinese autistic children and screen out potential metallic or microbial indicators of the disease. One hundred and thirty-six children (78 with ASD and 58 healthy controls) aged from 3 to 7 years were enrolled. The levels of lead, cadmium, arsenic, copper, zinc, iron, mercury, calcium and magnesium in hair samples from the children were analyzed. Fecal samples were also collected and the children's gut microbiota profiles were characterized by 16s rRNA sequencing. Concentrations of lead, arsenic, copper, zinc, mercury, calcium and magnesium were significantly higher in the ASD group than in the control group. Linear discriminant analysis effect size analysis indicated that the relative abundance of nine genera was increased in the autistic children. Redundancy analysis showed that arsenic and mercury were significantly associated with Parabacteroides and Oscillospira in the gut. A random forest model was trained with high accuracy (84.00%) and the metallic and microbial biomarkers of ASD were established. Our results indicate significant alterations in the trace element and gut microbiota profiles of Chinese children with ASD and reveal the potential pathogenesis of this disease in terms of metal metabolism and gut microecology.
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Transtorno do Espectro Autista/epidemiologia , Microbioma Gastrointestinal , Oligoelementos/metabolismo , Criança , Pré-Escolar , China , Humanos , Projetos Piloto , RNA Ribossômico 16SRESUMO
Lysine specific demethylase (LSD1) plays a pivotal role in epigenetic modulation of gene expression. Abberrant expression of LSD1 was associated with the progress and oncogenesis of multiple human cancers. Herein, we report the preliminary anti-LSD1 evaluation of the synthetic vanadium (V) complexes. Among them, complex 2 showed a moderate inhibitory effect against LSD1 with IC50 value of 19.0⯵M, as well as good selectivity over MAO-A/B. Complex 2 is the first vanadium based LSD1 inhibitor, which provides a novel scaffold for the development of LSD1 inhibitor.
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Histona Desmetilases/antagonistas & inibidores , Bases de Schiff/química , Compostos de Vanádio/química , Humanos , Ligantes , Simulação de Acoplamento Molecular , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: The aim of this study was to investigate the optimal timing for the resection of heterotopic ossification (HO) of the elbow. METHODS: We retrospectively reviewed 42 patients who were treated operatively for heterotopic ossification of the elbow from March 2010 to December 2014 at our institution. The patients were divided into early (before 12 months) and late (after 12 months) excision groups. In the early excision group (17 patients), the average time from the initial injury to HO excision was 7.4 (3-11) months, and in the late excision group (25 patients), the average time was 33.5 (12-240) months. Every patient was evaluated by range of motion (ROM), the Mayo Elbow Performance Score (MEPS), postoperative complications and HO recurrence. RESULTS: The preoperative mean ROM in the late excision group was greater than that of the early excision group, suggesting that the ROM is expected to increase even without surgery. Both early and late surgery increased ROM and MEPS, but early surgery improved ROM and MEPS more than late surgery did (p < .05). CONCLUSIONS: Early excision of HO can provide better elbow function, as indicated by ROM and MEPS. Considering that there were no notable differences in postoperative ROM and MEPS, HO recurrence, or postoperative complications, we concluded that early excision is safe and that the time from an elbow injury to surgery may be shortened. LEVEL OF EVIDENCE: Level III, therapeutic study.
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Lesões no Cotovelo , Articulação do Cotovelo , Ossificação Heterotópica , Complicações Pós-Operatórias , Adulto , Idoso , Intervenção Médica Precoce/métodos , Articulação do Cotovelo/fisiopatologia , Articulação do Cotovelo/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ossificação Heterotópica/etiologia , Ossificação Heterotópica/cirurgia , Avaliação de Processos e Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/prevenção & controle , Amplitude de Movimento Articular , Recidiva , Estudos Retrospectivos , Tempo para o TratamentoRESUMO
Objective To explore the application value of spectral CT quantitative analysis in differentiating adenocarcinoma or squamous carcinoma from inflammatory myofibroblastic tumor (IMT). Methods A total of 115 patients with 62 adenocarcinomas, 33 squamous carcinomas and 20 IMTs underwent spectral CT scans to obtain spectral images at arterial phase (AP) and venous phase (VP). The imaging data were analyzed retrospectively. The iodine concentration of adenocarcinoma, squamous carcinomas and IMT were measured. The normalized iodine concentration in AP (NICAP), normalized iodine concentration in VP (NICVP) and normalized iodine concentration difference between AP and VP (ICD) were calculated. The above quantitative parameters among three groups were analyzed with analysis of variance and ROC curve. Results NICAP (0.15 ± 0.04), NICVP (0.37 ± 0.08) and ICD(0.23 ± 0.06)of the adenocarcinoma were lower than those of IMT (0.21 ± 0.05,0.50 ± 0.06,0.28 ± 0.08). There were significant differences in NICAP, NICVP and ICD between adenocarcinoma and IMT (P<0.05). NICAP (0.13 ± 0.03), NICVP (0.35±0.06) and ICD (0.22±0.05) of the squamous carcinoma were lower than those of IMT (0.21± 0.05,0.50±0.06,0.28±0.08). The differences in NICAP, NICVP and ICD were significant between squamous carcinoma and IMT (P<0.05). There were no significant differences in NICAP, NICVP and ICD between adenocarcinoma and squamous carcinoma (P>0.05). The best spectral quantitative parameter for differentiating the adenocarcinoma from IMT was NICVP, which yielded a sensitivity of 92.3% and a specificity of 86.7%with the threshold of 0.425. NICVP was also the best spectral quantitative parameter for differentiating squamous carcinomas from IMT. With the threshold of 0.44, a sensitivity of 84.6% and a specificity of 92.3% were found. Conclusion Spectral CT imaging with the quantitative iodine concentration analysis may help to increase the accuracy of differentiating adenocarcinoma and squamous carcinoma from IMT.
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Objective To explore the application value of spectral CT quantitative analysis in differentiating adenocarcinoma or squamous carcinoma from inflammatory myofibroblastic tumor (IMT). Methods A total of 115 patients with 62 adenocarcinomas, 33 squamous carcinomas and 20 IMTs underwent spectral CT scans to obtain spectral images at arterial phase (AP) and venous phase (VP). The imaging data were analyzed retrospectively. The iodine concentration of adenocarcinoma, squamous carcinomas and IMT were measured. The normalized iodine concentration in AP (NICAP), normalized iodine concentration in VP (NICVP) and normalized iodine concentration difference between AP and VP (ICD) were calculated. The above quantitative parameters among three groups were analyzed with analysis of variance and ROC curve. Results NICAP (0.15 ± 0.04), NICVP (0.37 ± 0.08) and ICD(0.23 ± 0.06)of the adenocarcinoma were lower than those of IMT (0.21 ± 0.05,0.50 ± 0.06,0.28 ± 0.08). There were significant differences in NICAP, NICVP and ICD between adenocarcinoma and IMT (P<0.05). NICAP (0.13 ± 0.03), NICVP (0.35±0.06) and ICD (0.22±0.05) of the squamous carcinoma were lower than those of IMT (0.21± 0.05,0.50±0.06,0.28±0.08). The differences in NICAP, NICVP and ICD were significant between squamous carcinoma and IMT (P<0.05). There were no significant differences in NICAP, NICVP and ICD between adenocarcinoma and squamous carcinoma (P>0.05). The best spectral quantitative parameter for differentiating the adenocarcinoma from IMT was NICVP, which yielded a sensitivity of 92.3% and a specificity of 86.7%with the threshold of 0.425. NICVP was also the best spectral quantitative parameter for differentiating squamous carcinomas from IMT. With the threshold of 0.44, a sensitivity of 84.6% and a specificity of 92.3% were found. Conclusion Spectral CT imaging with the quantitative iodine concentration analysis may help to increase the accuracy of differentiating adenocarcinoma and squamous carcinoma from IMT.
RESUMO
Oleaginous microalgae have received a considerable attention as potential biofuel feedstock. However, lack of industry-suitable strain with lipid rich biomass limits its commercial applications. Targeted engineering of lipogenic pathways represents a promising strategy to enhance the efficacy of microalgal oil production. In this study, a type 2 diacylglycerol acyltransferase (DGAT), a rate-limiting enzyme in triacylglycerol (TAG) biosynthesis, was identified and overexpressed in heterokont oleaginous microalga Nannochloropsis oceanica for the first time. Overexpression of DGAT2 in Nannochloropsis increased the relative transcript abundance by 3.48-fold in engineered microalgae cells. TAG biosynthesis was subsequently accelerated by DGAT2 overexpression and neutral lipid content was significantly elevated by 69% in engineered microalgae. The fatty acid profile determined by GC-MS revealed that fatty acid composition was altered in engineered microalgae. Saturated fatty acids and polyunsaturated fatty acids were found to be increased whereas monounsaturated fatty acids content decreased. Furthermore, DGAT2 overexpression did not show negative impact on algal growth parameters. The present investigation showed that the identified DGAT2 would be a potential candidate for enhancing TAG biosynthesis and might facilitate the development of promising oleaginous strains with industrial potential.
Assuntos
Diacilglicerol O-Aciltransferase/genética , Engenharia Metabólica/métodos , Microalgas/metabolismo , Estramenópilas/enzimologia , Estramenópilas/metabolismo , Triglicerídeos/biossíntese , Diacilglicerol O-Aciltransferase/análise , Diacilglicerol O-Aciltransferase/metabolismo , Microalgas/genética , Filogenia , Triglicerídeos/análiseRESUMO
Endothelial progenitor cells (EPC) derived from the circulation may be used to enhance neovascularization. Since the combination of granulocyte colony-stimulating factor (GCSF) and CXCR4 antagonist AMD3100 efficiently mobilizes hematopoietic stem cells into peripheral circulation, it may increase the pool of endogenously circulating EPC. We tested this hypothesis by administering GCSF and AMD3100 to adult rabbits and rats, isolating mononuclear cells from peripheral blood by Ficoll density gradient centrifugation, and characterizing the blood-derived EPC based on morphology, immunophenotyping, gene expression and other functional analyses. These EPC showed clonal growth similar to that of human umbilical vein endothelial cells when cultured in complete EGM-2 medium on collagen I-precoated culture plates. The EPC exhibited a typical cobblestone-like morphology and were relatively homogeneous by the third passage. The cells expressed the typical endothelial marker CD31 based on flow cytometry and fluorescence microscopy, formed capillary-like structures when cultured in Matrigel, internalized DiI-acetylated low-density lipoprotein, bound Ulex europaeus agglutinin-1, and expressed CD31 and several other endothelial markers (VEGFR2, VE-cadherin, Tie-2, eNOS, vWF) at significantly higher levels than bone marrow-derived mesenchymal stem cells. These results suggest that the combination of GCSF and AMD3100 can efficiently release stem cells into peripheral circulation and generate EPC that show the desired morphological, immunophenotypic and functional characteristics. This minimally invasive approach may be useful for autologous cell transplantation for postnatal neovasculogenesis and tissue repair.