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OBJECTIVE: To explore the clinical phenotype and pathogenic variants in a Chinese pedigree affected with Smith-Lemli-Opitz syndrome. METHODS: Peripheral blood samples were collected from five members, including two affected ones, from the pedigree for the extraction of genomic DNA. Whole exome sequencing was carried out, and candidate variants were verified by Sanger sequencing as well as reverse transcription sequencing at the RNA level. RESULTS: The proband and another affected child from the pedigree showed mental retardation, dyskinesia, microcephaly, micrognathia, anteverted nares, and 2/3 toe syndactyly. The proband also had hypospadia, single upper incisor, and lower serum cholesterol level. Both children were found to harbor a paternally derived c.278C>T (p.T93M) variant and a maternally derived c.907G>A (p.G303R) variant of the DHCR7 gene. Both were known pathogenic mutations. CONCLUSION: The compound heterozygous mutations of c.278C>T (p.T93M) and c.907G>A (p.G303R) of the DHCR7 gene probably underlay the disease in this pedigree. Above finding has enabled early diagnosis and treatment of Smith-Lemli-Opitz syndrome.
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Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/genética , Síndrome de Smith-Lemli-Opitz , Niño , Pruebas Genéticas , Humanos , Linaje , Fenotipo , Síndrome de Smith-Lemli-Opitz/diagnóstico , Síndrome de Smith-Lemli-Opitz/genéticaRESUMEN
OBJECTIVE: To study the effect of ketogenic diet (KD) on neurobehavioral development, emotional and social behaviors, and life ability in children with global developmental delay (GDD). METHODS: A prospective case-control study was performed for hospitalized children with GDD, who were randomly divided into KD treatment group (n=40) and conventional treatment group (n=37). The children in both groups were given comprehensive rehabilitation training, and those in the KD treatment group were given modified Atkins diet in addition to the comprehensive rehabilitation training. The children in both groups were assessed with the Gesell Developmental Scale, Chinese version of Urban Infant-Toddler Social and Emotional Assessment (CITSEA)/Achenbach Child Behavior Checklist (CBCL), and Infants-Junior High School Students' Social Life Abilities Scale (S-M scale) before treatment and after 3, 6, and 9 months of treatment. The two groups were compared in terms of the improvements in neurobehavioral development, emotional and social behaviors, and social life ability. RESULTS: After 3, 6, and 9 months of treatment, the KD treatment group had significantly greater improvements in the scores of the adaptive, fine motor, and language quotients of the Gesell Developmental Scale compared with the conventional treatment group (P<0.05); the KD treatment group had significantly greater improvements in CITSEA/CBCL scores than the conventional treatment group (P<0.05). The KD treatment group had a greater improvement in the score of the S-M scale after 9 months of treatment (P<0.05). During the KD treatment, 6 children experienced diarrhea and 1 experienced mild urinary stones. CONCLUSIONS: KD can improve the neurobehavioral development and behavioral and emotional behaviors in children with GDD, and it has few adverse effects.
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Discapacidades del Desarrollo/dietoterapia , Dieta Cetogénica , Estudios de Casos y Controles , Niño , Preescolar , Discapacidades del Desarrollo/psicología , Emociones , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Estudios ProspectivosRESUMEN
Background: The global increase in the aging population presents considerable challenges, particularly regarding cognitive impairment, a major concern for public health. This study investigates the association between the triglyceride-glucose (TyG) index, a measure of insulin resistance, and the risk of cognitive impairment in the elderly. Methods: This prospective cohort study enrolled 2,959 participants aged 65 and above from the 2015 and 2020 waves of the China Health and Retirement Longitudinal Study (CHARLS). The analysis employed a logistic regression model to assess the correlation between the TyG index and cognitive impairment. Results: The study included 2,959 participants, with a mean age of 71.2 ± 5.4 years, 49.8% of whom were female. The follow-up in 2020 showed a decrease in average cognitive function scores from 8.63 ± 4.61 in 2015 to 6.86 ± 5.45. After adjusting for confounding factors, a significant association was observed between TyG index quartiles and cognitive impairment. Participants in the highest quartile (Q4) of baseline TyG had a higher risk of cognitive impairment compared to those in the lowest quartile (Q1) (odds ratio [OR]: 1.97, 95% confidence intervals [CI]: 1.28-2.62, P<0.001). Conclusion: The study highlights a significant connection between elevated TyG index levels and cognitive impairment among older adults in China. These findings suggest that targeted interventions to reduce the TyG index could mitigate cognitive impairment and potentially lower the incidence of dementia.
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Glucemia , Cognición , Disfunción Cognitiva , Vida Independiente , Triglicéridos , Humanos , Femenino , Masculino , Anciano , Triglicéridos/sangre , Disfunción Cognitiva/sangre , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/diagnóstico , Cognición/fisiología , Estudios Prospectivos , China/epidemiología , Glucemia/análisis , Glucemia/metabolismo , Estudios Longitudinales , Anciano de 80 o más Años , Estudios de Cohortes , Resistencia a la Insulina , Factores de RiesgoRESUMEN
This article studies the stability problem of discrete-time switched positive linear systems (SPLSs) with marginally stable subsystems. Based on the weak common linear copositive Lyapunov function (weak CLCLF) approach, the switching property and the state component property are combined to ensure the asymptotic stability of SPLSs under three types of switching signals. First, considering the transfer-restricted switching signal described by the switching digraph, novel cycle-dependent joint path conditions are proposed in combination with state component digraphs. Second, under the time interval sequence, two types of path conditions are constructed for designing switching schemes. Third, necessary and sufficient conditions for the asymptotic stability of SPLSs under arbitrary switching are established. Finally, three examples are provided to illustrate the effectiveness of the proposed method.
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Fuzzy rough set (FRS) theory is generally used to measure the uncertainty of data. However, this theory cannot work well when the class density of a data distribution differs greatly. In this work, a relative distance measure is first proposed to fit the mentioned data distribution. Based on the measure, a relative FRS model is introduced to remedy the mentioned imperfection of classical FRSs. Then, the positive region, negative region, and boundary region are defined to measure the uncertainty of data with the relative FRSs. Besides, a relative fuzzy dependency is defined to evaluate the importance of features to decision. With the proposed feature evaluation, we propose a feature selection algorithm and design a classifier based on the maximal positive region. The classification principle is that an unlabeled sample will be classified into the class corresponding to the maximal degree of the positive region. Experimental results show the relative fuzzy dependency is an effective and efficient measure for evaluating features, and the proposed feature selection algorithm presents better performance than some classical algorithms. Besides, it also shows the proposed classifier can achieve slightly better performance than the KNN classifier, which demonstrates that the maximal positive region-based classifier is effective and feasible.
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Magnesium-lithium alloy is the lightest metal alloy material so far, and the ultra-thin plate is also one of the main trends in the future development of Mg-Li alloy. In order to explore how to prepare LZ91 ultra-thin Mg-Li alloy, this topic adopts the combination of the finite element method (FEM) and visco-plastic self-consistent (VPSC) calculation, electron back-scattered diffraction (EBSD) and tensile experiment, and uses the asymmetric warm rolling process to realize the processing of ultra-thin LZ91 Mg-Li alloy plate with a thickness of 0.25 mm. The experimental results show that the maximum basal texture strengths of 1 mm initial plate and 0.25 mm ultra-thin rolled plate are 36.02 mud and 29.19 mud, respectively. The asymmetric warm rolling process not only reduces the basal texture strength but also significantly refines the grains. The tensile strength and yield strength of 0.25 mm ultra-thin rolled plate along the rolling direction reached 206.8 MPa and 138.4 MPa, respectively. This has a positive effect on the mechanical properties of subsequent materials. VPSC results show that the base slip is the main factor in Mg-Li alloy asymmetric warm rolling, and a large number of tensile twinning are initiated due to the coordinated deformation of the body-centered cubic (BCC) phase, which is beneficial to improve the plastic deformation capacity of Mg-Li alloy.
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Genetic mutations in HSF4 cause congenital cataracts. HSF4 exhibits both positive and negative regulation on the transcription of heat shock and non-heat shock proteins during lens development, and its activity is regulated by posttranslational modifications. Biotin is an essential vitamin that regulates gene expression through protein biotinylation. In this paper, we report that HSF4b is negatively regulated by biotinylation. Administration of biotin or ectopic bacterial biotin ligase BirA increases HSF4b biotinylation at its C-terminal amino acids from 196 to 493. This attenuates the HSF4b-controlled expression of αB-crystallin in both lens epithelial cells and tested HEK293T cells. HSF4b interacts with holocarboxylase synthetase (HCS), a ubiquitous enzyme for catalyzing protein biotinylation in mammal. Ectopic HA-HCS expression downregulates HSF4b-controlled αB-crystallin expression. Lysine-mutation analyses indicate that HSF4b/K444 is a potential biotinylation site. Mutation K444R reduces the co-precipitation of HSF4b by streptavidin beads and biotin-induced reduction of αB-crystallin expression. Mutations of other lysine residues such as K207R/K209R, K225R, K288R, K294R and K355R in HSF4's C-terminal region do not affect HSF4's expression level and the interaction with streptavidin, but they exhibit distinct regulation on αB-crystallin expression through different mechanisms. HSF4/K294R leads to upregulation of αB-crystallin expression, while mutations K207R/K209R, K225R, K288R, K255R and K435R attenuate HSF4's regulation on αB-crystallin expression. K207R/K209R blocks HSF4 nuclear translocation, and K345R causes HSF4 destabilization. Taken together, the data reveal that biotin maybe a novel factor in modulating HSF4 activity through biotinylation.
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Plant-specific TEOSINTE BRANCHED 1, CYCLOIDEA, PROLIFERATING CELL FACTORS (TCP) transcription factors have versatile functions in plant growth, development and response to environmental stress. Despite blueberry's value as an important fruit crop, the TCP gene family has not been systematically studied in this plant. The current study identified blueberry TCP genes (VcTCPs) using genomic data from the tetraploid blueberry variety 'Draper'; a total of 62 genes were obtained. Using multiple sequence alignment, conserved motif, and gene structure analyses, family members were divided into two subfamilies, of which class II was further divided into two subclasses, CIN and TB1. Synteny analysis showed that genome-wide or segment-based replication played an important role in the expansion of the blueberry TCP gene family. The expression patterns of VcTCP genes during fruit development, flower bud dormancy release, hormone treatment, and tissue-specific expression were analyzed using RNA-seq and qRT-PCR. The results showed that the TB1 subclass members exhibited a certain level of expression in the shoot, leaf, and bud; these genes were not expressed during fruit development, but transcript levels decreased uniformly during the release of flower bud dormancy by low-temperature accumulation. The further transgenic experiments showed the overexpression of VcTCP18 in Arabidopsis significantly decreased the seed germination rate in contrast to the wild type. The bud dormancy phenomena as late-flowering, fewer rosettes and main branches were also observed in transgenic plants. Overall, this study provides the first insight into the evolution, expression, and function of VcTCP genes, including the discovery that VcTCP18 negatively regulated bud dormancy release in blueberry. The results will deepen our understanding of the function of TCPs in plant growth and development.
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Fuzzy rough sets (FRSs) are considered to be a powerful model for analyzing uncertainty in data. This model encapsulates two types of uncertainty: 1) fuzziness coming from the vagueness in human concept formation and 2) roughness rooted in the granulation coming with human cognition. The rough set theory has been widely applied to feature selection, attribute reduction, and classification. However, it is reported that the classical FRS model is sensitive to noisy information. To address this problem, several robust models have been developed in recent years. Nevertheless, these models do not consider a statistical distribution of data, which is an important type of uncertainty. Data distribution serves as crucial information for designing an optimal classification or regression model. Thus, we propose a data-distribution-aware FRS model that considers distribution information and incorporates it in computing lower and upper fuzzy approximations. The proposed model considers not only the similarity between samples, but also the probability density of classes. In order to demonstrate the effectiveness of the proposed model, we design a new sample evaluation index for prototype-based classification based on the model, and a prototype selection algorithm is developed using this index. Furthermore, a robust classification algorithm is constructed with prototype covering and nearest neighbor classification. Experimental results confirm the robustness and effectiveness of the proposed model.
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BACKGROUND: SARS coronavirus has been identified as the cause of severe acute respiratory syndrome (SARS). Few tests allow confirmation or exclusion of SARS within the first few days of infection. A gene chip is a useful tool for the study of microbial infections mainly for its capability of performing multi-target analysis in a single test. OBJECTIVES: Investigate the possibility of early detection of SARS virus from clinical samples using the gene chip-based method. STUDY DESIGN: We purified RNA from SARS-CoV obtained from routinely collected peripheral blood and sputum samples of 34 patients who had been identified as probable SARS patients by following the interim U.S. case definition. Four segments of the SARS-CoV were amplified using reverse transcription-nested PCR and the products examined using the 70-mer gene chips for SARS-CoV detection. RESULTS: A blind-test of both peripheral blood and sputum specimens lead to the positive detection of SARS-CoV in 31 out of 34 patients. SARS-CoV was not found in peripheral blood or sputum specimens from three patients. Two of the 34 patients were only 3 days post-onset of symptoms and were subsequently confirmed to be SARS positive. Our results indicate that the gene chip-based molecular test is specific for SARS-CoV and allows early detection of patients with SARS with detection rate about 8% higher than the single PCR test when the sputum sample is available.
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Técnicas de Diagnóstico Molecular , Análisis de Secuencia por Matrices de Oligonucleótidos , Síndrome Respiratorio Agudo Grave/diagnóstico , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/genética , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/aislamiento & purificación , Sangre/virología , China , Diagnóstico Precoz , Humanos , Reacción en Cadena de la Polimerasa , ARN Viral/análisis , ARN Viral/aislamiento & purificación , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sensibilidad y Especificidad , Síndrome Respiratorio Agudo Grave/genética , Esputo/virologíaRESUMEN
Three series of multicomponent silicone hydrogels were prepared by the copolymerization of two hydrophobic silicon monomers bis(trimethylsilyloxy) methylsilylpropyl glycerol methacrylate (SiMA) and tris(trimethylsiloxy) 3-methacryloxypropylsilane (TRIS) with three hydrophilic monomers. The surface hydrophilicity of the silicone hydrogels was characterized by contact angle measurements, and an interesting phenomenon was found that the silicone hydrogels made from less hydrophobic monomer SiMA possess more hydrophobic surfaces than those made from TRIS. The surface properties such as morphology and elemental composition of the silicone hydrogels were explored by scanning electron microscopy (SEM) imaging and energy dispersive spectrometry (EDS) analysis, and their relationships with the surface hydrophilicity were investigated in details. The results show neither the surface morphology nor the elemental composition has obvious impact on the surface hydrophilicity. Atomic force microscopy (AFM) imaging revealed that SiMA hydrogel had a more significant phase separation structure, which also made its surface uneven: a lot of tiny holes were observed on the surface. This surface phase separation structure made SiMA hydrogel more difficult to be wetted by water or PBS buffer, i.e., more hydrophobic than TRIS hydrogel. On the basis of these results, we propose that the phase separation structure as well as the nature of silicon monomers might be the fundamental reasons of surface hydrophilicity. These results could help to design a silicone hydrogel with better surface properties and wider application.
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Hidrogeles/química , Interacciones Hidrofóbicas e Hidrofílicas , Siliconas/química , Metacrilatos/química , Silanos/química , Propiedades de SuperficieRESUMEN
The rapid and accurate detection and identification of food-borne pathogenic bacteria is critical for food safety. In this paper, we describe a rapid (<4 h) high-throughput detection and identification system that uses universal polymerase chain reaction (PCR) primers to amplify a variable region of bacterial the 16S rRNA gene, followed by reverse hybridization of the products to species-specific oligonucleotide probes on a chip. This procedure was successful in discriminating 204 strains of bacteria from pure culture belonging to 13 genera of bacteria. When this method was applied directly to 115 strains of bacteria isolated from foods, 112/115 (97.4%) were correctly identified; two strains were indistinguishable due to weak signal, while one failed to produce a PCR product. The array was used to detect and successfully identify two strains of bacteria from food poisoning outbreak samples, giving results through hybridization that were identical to those obtained by traditional methods. The sensitivity of the microarray assay was 10(2) CFU of bacteria. Thus, the oligonucleotide microarray is a powerful tool for the detection and identification of pathogens from foods.
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Bacterias/aislamiento & purificación , Cartilla de ADN/genética , Microbiología de Alimentos , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Bacterias/clasificación , Bacterias/genética , Bacterias/patogenicidad , Análisis de los Alimentos , ARN Bacteriano/genética , ARN Ribosómico 16S/genética , Sensibilidad y Especificidad , Especificidad de la Especie , VirulenciaRESUMEN
The response of the yeast Saccharomyces cerevisiae to two polyene antibiotics, amphotericin B and nystatin, was studied by genomic expression profiling. The two agents produced highly similar expression pattern changes, which was consistent with their known identical mechanisms of action on cell membranes. Detailed analysis was focused on the amphotericin B-treated sample in this study. Our data showed that genes involved in mitochondrial ribosomal protein synthesis were more severely repressed than those in the cytoplasm, which might contribute to the cytotoxicity of amphotericin B. To counteract the leakage of intracellular nutrients and ions from the pores in the cell membrane caused by amphotericin B, c. 17 genes involved in transport facilitation were induced, presumably to allow more efficient uptake of nutrients and ions. The expression level of five genes involved in ergosterol synthesis dropped and three genes related to cell wall biogenesis were induced, indicating that the cell membrane and cell wall were also affected by the presence of polyene antibiotics. It was observed that the pleiotropic drug resistance network in yeast cells was activated after exposure to amphotericin B, possibly contributing to the acquisition of amphotericin B resistance. Part of the gene expression alteration measured by microarray was confirmed by quantitative RT-PCR.