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This study aimed to identify different symptom trajectories based on the severity of depression symptoms within a 2-month follow-up, and to explore predictive factors for different symptom trajectories. Three hundred and ninety-two adults diagnosed with major depressive disorder (MDD) were recruited from two longitudinal cohorts. Patients received antidepressant treatment as usual, and the depression symptoms were evaluated by the 17-item Hamilton depression rating scale (HAMD-17) at baseline, two weeks, and eight weeks. Based on the HAMD-17 scores, different trajectories of symptom change were distinguished by applying Growth Mixture Modeling (GMM). Furthermore, the baseline sociodemographic, clinical, and cognitive characteristics were compared to identify potential predictors for different trajectories. Through GMM, three unique depressive symptom trajectories of MDD patients were identified: (1) mild-severity class with significant improvement (Mild, n = 255); (2) high-severity class with significant improvement (High, n = 39); (3) moderate-severity class with limited improvement (Limited, n = 98). Among the three trajectories, the Mild class had a relatively low level of anxiety symptoms at baseline, whereas the High class had the lowest education level and the worst cognitive performance. Additionally, participants in the Limited class exhibited an early age of onset and experienced a higher level of emotional abuse. MDD patients could be categorised into three distinct latent subtypes through different symptom trajectories in this study, and the characteristics of these subtype patients may inform identifications for trajectory-specific intervention targets.
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A fundamental understanding of metal active sites in single-atom catalysts (SACs) is important and challenging in the development of high-performance catalyst systems. Here, a highly efficient and straightforward molten-salt-assisted approach is reported to create atomically dispersed cobalt atoms supported over vanadium pentoxide layered material, with each cobalt atom coordinated with four neighboring oxygen atoms. The liquid environment and the strong polarizing force of the molten salt at high temperatures potentially favor the weakening of VO bonding and the formation of CoO bonding on the vanadium oxide surface. This cobalt SAC achieves extraordinary catalytic efficiency in acceptorless dehydrogenative coupling of alcohols with amines to give imines, with more than 99% selectivity under almost 100% conversion within 3 h, along with a high turnover frequency (TOF) of 5882 h-1 , exceeding those of previously reported benchmarking catalysts. Moreover, it delivers excellent recyclability, reaction scalability, and substrate tolerance. Density functional theory (DFT) calculations further confirm that the optimized coordination environment and strong electronic metal-support interaction contribute significantly to the activation of reactants. The findings provide a feasible route to construct SACs at the atomic level for use in organic transformations.
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BACKGROUND: Treatment non-response and recurrence are the main sources of disease burden in major depressive disorder (MDD). However, little is known about its neurobiological mechanism concerning the brain network changes accompanying pharmacotherapy. The present study investigated the changes in the intrinsic brain networks during 6-month antidepressant treatment phase associated with the treatment response and recurrence in MDD. METHODS: Resting-state functional magnetic resonance imaging was acquired from untreated patients with MDD and healthy controls at baseline. The patients' depressive symptoms were monitored by using the Hamilton Rating Scale for Depression (HAMD). After 6 months of antidepressant treatment, patients were re-scanned and followed up every 6 months over 2 years. Traditional statistical analysis as well as machine learning approaches were conducted to investigate the longitudinal changes in macro-scale resting-state functional network connectivity (rsFNC) strength and micro-scale resting-state functional connectivity (rsFC) associated with long-term treatment outcome in MDD. RESULTS: Repeated measures of the general linear model demonstrated a significant difference in the default mode network (DMN) rsFNC change before and after the 6-month antidepressant treatment between remitters and non-remitters. The difference in the rsFNC change over the 6-month antidepressant treatment between recurring and stable MDD was also specific to DMN. Machine learning analysis results revealed that only the DMN rsFC change successfully distinguished non-remitters from the remitters at 6 months and recurring from stable MDD during the 2-year follow-up. CONCLUSION: Our findings demonstrated that the intrinsic DMN connectivity could be a unique and important target for treatment and recurrence prevention in MDD.
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Trastorno Depresivo Mayor , Humanos , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/tratamiento farmacológico , Red en Modo Predeterminado , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Antidepresivos/uso terapéutico , Vías Nerviosas/diagnóstico por imagen , Resultado del TratamientoRESUMEN
This study aimed to elucidate the contribution of childhood maltreatment (CM) and the disease of major depressive disorder (MDD) on cognitive function in medication-free patients in a current depressive episode, and to examine the effect of CM on the improvement of cognitive function after treatment with antidepressants. One hundred and fifty-three unmedicated patients with MDD and 142 healthy controls (HCs) underwent clinical interviews. CM assessment was performed using the Childhood Trauma Questionnaire (CTQ), and a battery of comprehensive neurocognitive tests was used to assess the participants' executive function, processing speed, attention, and memory. After 6 months of treatment with antidepressants, the neurocognitive tests were reperformed in patients with MDD and HCs. There was a significant main effect of MDD on all four cognitive domains, while the main effect of CM was only significant on memory. No significant interactive effect was found between MDD and CM on any of the cognitive domains. In the MDD group, higher CTQ total score was predictive of poorer memory performance. After treatment, significant main effects of treatment and MDD were found on all four cognitive domains in remitted patients with MDD. No significant main effect of CM or three-way interaction effect of treatment × MDD × CM was found on any of the cognitive domains. The disease of MDD contributed to impairments in all four cognitive domains. CM independently contributed to memory impairment in patients in a current depressive episode, with higher severity of CM predictive of poorer memory performance.
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Maltrato a los Niños , Disfunción Cognitiva , Trastorno Depresivo Mayor , Humanos , Niño , Trastorno Depresivo Mayor/complicaciones , Trastorno Depresivo Mayor/tratamiento farmacológico , Cognición , Función Ejecutiva , Antidepresivos/uso terapéutico , Disfunción Cognitiva/etiología , Disfunción Cognitiva/tratamiento farmacológicoRESUMEN
BACKGROUND: Previous studies suggested that childhood maltreatment is associated with poor health outcomes. While not everyone who experiences abuse as a child goes on to experience poor mental health, some traumatized people are grown to be more resilient than others. Few studies have examined the association between childhood maltreatment and adult resilience. This study aimed to determine different relationships between specific types and features of childhood maltreatment with adult resilience among Chinese with Major Depressive Disorder (MDD) and healthy controls (HCs). METHODS: A total of 101 patients with MDD and 116 participants in the healthy control (HC) group from Zhumadian Psychiatric Hospital and its nearby communities were included in this analysis. Childhood maltreatment was assessed retrospectively using Childhood Trauma Questionnaire (CTQ). Adults' resilience was assessed by the Connor-Davidson Resilience Scale (CD-RISC). Generalized linear models were applied between childhood maltreatment (specific types and features) and resilience adjusting for covariates. RESULTS: The total score of CD-RISC and factor scores of strength, optimism, and tenacity in the HC group were higher than those in the MDD group. CTQ total score had a negative association with optimism score among participants in MDD (ß=-0.087, P < 0.001) and HC (ß=-0.074, P = 0.023) groups. Higher emotional neglect (EN) score (ß=-0.169, P = 0.001) and physical neglect (PN) score (ß=-0.153, P = 0.043) were related to a worse optimism score in MDD group. Emotional abuse (EA) score was associated with a worse tenacity score (ß=-0.674, P = 0.031) in MDD group. For participants in HC group, higher EN and PN scores were related to worse resilience scores (tenacity, strength, and optimism). CONCLUSIONS: Patients with MDD showed lower optimism than HCs. Childhood maltreatment, especially childhood negect, independently contributed to optimism, with more severe childhood maltreatment predictive of worse performance of optimism. EA in childhood was also linked to worse tenacity in adult patients with MDD.
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Experiencias Adversas de la Infancia , Trastorno Depresivo Mayor , Adulto , Niño , Humanos , Abuso Emocional , Estudios Retrospectivos , Pueblos del Este de AsiaRESUMEN
BACKGROUND: Dysfunctional attitudes, which are characterized by distorted self-cognitions, were considered to be linked to personality traits. It was found that certain personality traits may predict dysfunctional attitudes in patients with major depressive disorder (MDD). Nonetheless, the relationship between personality traits and dysfunctional attitudes remains under-researched. AIMS: The aim of this study is to examine the relationship between specific domains of Sixteen Personality Factor (16PF) and dysfunctional attitudes in Chinese participants with or without MDD. In addition, the present study explores the associations between 16PF and eight subtypes of dysfunctional attitudes, based on the proposed eight-factor structure of the Chinese version of the Dysfunctional Attitude Scale-Form A (C-DAS-A). METHODS: One hundred and sixty-eight participants with MDD and 130 healthy participants were included in the study (Trial Registration Number: ChiCTR1800014591). Personality was assessed using the 16PF Questionnaire. Dysfunctional attitudes were measured through the C-DAS-A. RESULTS: The 16PF dimensions associated with dysfunctional attitudes and the eight subtypes were mainly concentrated in the four anxiety facets including factors C, L, O, and Q4, in both MDD and HC groups. There were significant differences in the 16 PF dimensions that would explain dysfunctional attitudes between the two groups, which were as follows: factors C, G, and O in the MDD group, and factors L and Q4 in the HC group. CONCLUSIONS: Personality traits, especially the anxiety-related personality traits, were distinctly associated with the development of dysfunctional attitudes in people with or without MDD.
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Trastorno Depresivo Mayor , Humanos , Estudios de Casos y Controles , Actitud , Personalidad , CogniciónRESUMEN
Basic helix-loop-helix (bHLH) is the second largest family of transcription factors that widely exist in plants and animals, and plays a key role in a variety of biological processes. As an important forage crop worldwide, little information is available about the bHLH family in orchardgrass (Dactylis glomerata L.), although a huge number of bHLH family have been identified and characterized in plants. In this study, we performed genome-wide analysis of bHLH transcription factor family of orchardgrass and identified 132 DgbHLH genes. The phylogenetic tree was constructed by using bHLH proteins of orchardgrass, with Arabidopsis thaliana and Oryza sativa bHLH proteins, to elucidate their homology and classify them into 22 subfamilies. The results of conserved motifs and gene structure support the classification of DgbHLH family. In addition, chromosomal location and gene duplication events of DgbHLH genes were further studied. Transcriptome data exhibited that DgbHLH genes were differentially expressed in different tissues of orchardgrass. We analyzed the gene expression level of 12 DgbHLH genes in orchardgrass under three types of abiotic stresses (heat, salt, and drought). Finally, heterologous expression assays in yeast indicated that DgbHLH46 and DgbHLH128 may enhance the resistance to drought and salt stress. Furthermore, DgbHLH128 may also be involved in abiotic stress by binding to the MYC element. Our study provides a comprehensive assessment of DgbHLH family of orchardgrass, revealing new insights for enhancing gene utilization and improving forage performance.
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Arabidopsis , Dactylis , Animales , Dactylis/genética , Dactylis/metabolismo , Tolerancia a la Sal/genética , Sequías , Filogenia , Arabidopsis/genética , Arabidopsis/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Estrés Fisiológico/genética , Plantas , Regulación de la Expresión Génica de las PlantasRESUMEN
Selective aerobic oxidation of alcohols offers an attractive means to address challenges in the modern chemical industry, but the development of non-noble metal catalysts with superior efficacy for this reaction remains a grand challenge. Here, this study reports on such a catalyst based on atomically defined undercoordinated copper atoms over nitrogen-doped carbon support as an efficient, durable, and scalable heterogeneous catalyst for selective aerobic oxidation of alcohols. This catalyst exhibits extremely high intrinsic catalytic activity (TOF of 7692 h-1 ) in the oxidation of cinnamyl alcohol to afford cinnamaldehyde, along with exceptional recyclability (at least eight cycles), scalability, and broad substrate scope. DFT calculations suggest that the high activity derives from the low oxidation state and the unique coordination environment of the copper sites in the catalyst. These findings pave the way for the design of highly active and stable single atom catalysts to potentially address challenges in synthetic chemistry.
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The facile creation of high-performance single-atom catalysts (SACs) is intriguing in heterogeneous catalysis, especially on 2D transition-metal dichalcogenides. An efficient spontaneous reduction approach to access atomically dispersed iron atoms supported over defect-containing MoS2 nanosheets is herein reported. Advanced characterization methods demonstrate that the isolated iron atoms situate atop of molybdenum atoms and coordinate with three neighboring sulfur atoms. This Fe SAC delivers exceptional catalytic efficiency (1 atm O2 @ 120 °C) in the selective oxidation of benzyl alcohol to benzaldehyde, with 99% selectivity under almost 100% conversion. The turnover frequency is calculated to be as high as 2105 h-1 . Moreover, it shows admirable recyclability, storage stability, and substrate tolerance. Density functional theory calculations reveal that the high catalytic activity stems from the optimized electronic structure of single iron atoms over the MoS2 support.
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Bivalves have evolved effective strategies to combat different pathogens in the environment. They rely on innate immunity to deal with the invasion of various bacteria, viruses, and other microorganisms. However, the molecular mechanisms underlying the responses remain largely unknown. Herein, we constructed 21 transcriptomes of the hemocytes after lipopolysaccharide (LPS), peptidoglycan (PGN) and polyinosinic-polycytidylic acid (poly(I:C)) stimulation to investigate the molecular mechanisms underlying adaptations and plastic responses to different pathogen-related molecular patterns (PAMPs) in pearl oyster Pinctada fucata martensii. Transcriptome analysis revealed 1986-3427 responsive genes enriched in the major immune and cell cycle-related pathways at different times after PAMP stimulation, and the expression patterns of genes under these pathways are complex and diverse. Moreover, "lysosomes" were enriched 6 h after LPS and PGN stimulation, while "peroxisomes" were only enriched in poly(I:C) group. These results suggest different response strategies of pearl oyster to different PAMPs. Furthermore, we identified 261 pattern-recognition receptors (PRRs) including 4 retinoic acid-inducible gene I-like receptors, 38 NOD-like receptors, 83 Toll-like receptors, and 136 C-type lectins in the genome of P. f. martensii. The diverse expression patterns of these PRRs after different PAMP stimulation indicated that pearl oyster evolved complex and specific recognition systems due to tandem repeat and diverse domain combination, which may help pearl oyster cope with the different pathogens in the environment. The present study improved our understanding of the molecular response of pearl oyster to different PAMP stimulation.
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Pinctada , Animales , Moléculas de Patrón Molecular Asociado a Patógenos/farmacología , Moléculas de Patrón Molecular Asociado a Patógenos/metabolismo , Lipopolisacáridos/farmacología , Lipopolisacáridos/metabolismo , Perfilación de la Expresión Génica , Transcriptoma , Receptores de Reconocimiento de Patrones/genéticaRESUMEN
OBJECTIVES: Major depressive disorder (MDD) patients with anhedonia tend to have a poor prognosis. The underlying imaging basis for anhedonia in MDD remains largely unknown. The relationship between nodal properties and anhedonia in MDD patients need to be further investigated. Herein, this study aims to explore differences of cerebral functional node characteristics in MDD patients with severe anhedonia (MDD-SA) and MDD patients with mild anhedonia (MDD-MA) before and after the antidepressant treatment. METHODS: Ninety participants with current MDD were recruited in this study. 24-Item Hamilton Depression Scale (HAMD-24) and Snaith-Hamilton Pleasure Scale (SHAPS) were used to assess the severity of depression and anhedonia at baseline and the end of 6-months treatment. The MDD patients who scored above the 25th percentile on the SHAPS were assigned to an MDD-SA group (n=19), while those who scored below the 25th percentile were assigned to an MDD-MA group (n=18). All patients in the 2 groups received antidepressant treatment. Functional magnetic resonance imaging (fMRI) images of all the patients were collected at baseline and the end of 6-months treatment. Graph theory was applied to analyze the patients' cerebral functional nodal characteristics, which were measured by efficiency (ei) and degree (ki). RESULTS: Repeated measures 2-factor ANCOVA showed significant main effects on group on the ei and ki values of left superior frontal gyrus (LSFG) (P=0.003 and P=0.008, respectively), and on the ei and ki values of left medial orbital-frontal gyrus (LMOFG) (P=0.004 and P=0.008, respectively). Compared with the MDD-MA group, the significantly higher ei and ki values of the LSFG (P=0.015 and P=0.021, respectively), and the significantly higher ei and ki values of the LMOFG (P=0.015 and P=0.037, respectively) were observed in the MDD-SA group at baseline. Meanwhile, higher SHAPS scores could result in higher ei and ki values of LSFG (P=0.019 and P=0.026, respectively), and higher ei value of LMOFG (P=0.040) at baseline; higher SHAPS scores could result in higher ei values of LSFG (P=0.049) at the end of 6-months treatment. The multiple linear regression analysis revealed that sex were negatively correlated with the ei and ki values of LSFG (r= -0.014, P=0.004; r=-1.153, P=0.001, respectively). The onset age of MDD was negatively correlated with the ki value of LSFG (r=-0.420, P=0.034) at the end of 6-months treatment. We also found that SHAPS scores at baseline were positively correlated with the HAMD-24 scores (r=0.387, P=0.022) at the end of 6-months treatment. CONCLUSIONS: There are obvious differences in nodal properties between the MDD-SA and the MDD-MA patients, such as the high ei of LSFG in the MDD-SA patients, which may be associated with the severity of anhedonia. These nodal properties could be potential biomarkers for the prognosis of MDD. The increased ei and ki values in the LSFG of MDD-SA patients may underlie a compensatory mechanism or protective mechanism. The mechanism may be an important component of the pathological mechanism of MDD-SA. The poor prognosis in the MDD-SA patients suggests that anhedonia may predict a worse prognosis in MDD patients. Sex and onset age of MDD may affect the nodal properties of LSFG at baseline and the end of 6-months treatment.
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Trastorno Depresivo Mayor , Anhedonia , Antidepresivos/uso terapéutico , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/tratamiento farmacológico , Humanos , Lactante , Recién Nacido , Imagen por Resonancia Magnética , Corteza PrefrontalRESUMEN
OBJECTIVE: The aim of the study was to explore the tendency of modified electroconvulsive therapy (MECT)-related working memory and subjective memory deficits in depressed patients. METHODS: Sixty patients with unipolar/bipolar depression were prepared and enrolled for MECT and 56 subjects were enrolled as healthy controls (HCs). Their demographics (sex, age, body mass index, years of schooling, etc) and clinical characteristics (dosage and number of MECT, etc) were compared. Depression severity, working memory, and subjective memory were measured using the Hamilton Depression Rating Scale 17 (HAMD17), a Digit Span Backwards (DSB), and self-reported assessments, respectively. Measurements were taken at baseline, within 24 hours after each MECT session, and in every month for a 6-month follow-up period. RESULTS: (a) The patients had poorer performance than the HCs on DSB and HAMD17 at baseline, and the DSB score and HAMD17 total scores were negatively correlated. However, after the second MECT session, the patients' HAMD17 score was significantly improved compared with that at the baseline (P < 0.05), whereas the DSB score showed no significant difference compared with the HCs (P > 0.05). (b) After the first MECT session, 62% of the patients reported subjective memory deficits, which were exacerbated over the subsequent sessions and relieved with antidepressant treatment during the follow-up period. (c) The risk factors for prolonged subjective memory deficits were overweight and the maximum MECT dosage/age (dosage/age = the percentage of output part of total dosage × 100/age, unit: 1/year) ≥ 1.5/year (odds ratio [OR] = 15.36 and 7.98). CONCLUSIONS: Depressed patients showed poorer working memory than the HCs. Such memory deficit may be aggravated by MECT, although it may improve with the relief of depression. Although subjective memory deficits can occur after the first MECT session and gradually recover after the treatment, they may last for 6 months or longer. Persistent deficits may be related to being overweight and having a high MECT dosage.
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Trastorno Bipolar/terapia , Trastorno Depresivo Mayor/terapia , Terapia Electroconvulsiva/métodos , Trastornos de la Memoria/etiología , Memoria a Corto Plazo , Adolescente , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Vitamin D is a fat-soluble prohormone that can be activated both systemically and within individual tissues. Our lab has previously demonstrated that the corneal epithelium can activate vitamin D and that the vitamin D metabolites 1,25(OH)2D3 and 24R,25(OH)2D3 can affect corneal epithelial migration, proliferation, and tight and gap junction function. These vitamin D-derived metabolites signal through the vitamin D receptor (VDR). The purpose of this study was to specifically determine the effects of 1,25(OH)2D3 and 24R,25(OH)2D3 on corneal epithelial cell gap junction proteins. Connexin (Cx) 26, 30 and 43 protein expression was detected in a human corneal epithelial cell line (HCEC), wild type and vitamin D receptor knockout (VDR-/-) mouse corneas, and cultured mouse primary epithelial cells (MPCEC). In vitro gap junction function was assessed using the scrape loading/dye transfer assay. HCEC and MPCEC were treated with 1,25(OH)2D3 or 24R,25(OH)2D3. Western blotting was used to detect gap junction proteins. Vitamin D3 effects on epithelial intracellular Ca++ (Ca++i) were determined using the dye Cal-520. Cx26 and Cx43 protein levels were significantly increased in HCEC and MPCEC treated with both 1,25(OH)2D3 and 24R,25(OH)2D3. Cx30 and Cx43 protein levels were also significantly increased in VDR-/- MPCEC. In vitro gap junction connectivity was significanlty enhanced in HCEC and MPCEC cultured with 24R,25(OH)2D3 and 1,25(OH)2D3. Ca++i was not affected by 1,25(OH)2D3 or 24R,25(OH)2D3 in HCEC or MPCEC. We conclude that both 1,25(OH)2D3 and 24R,25(OH)2D3 are positive regulators of connexin proteins and gap junction communication in the corneal epithelium. These vitamin D metabolites appear to signal through both VDR-dependent and -independent pathways. The effects of vitamin D on corneal epithelial gap junctions do not seem to be dependent on Ca++i.
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24,25-Dihidroxivitamina D 3/farmacología , Calcitriol/farmacología , Conexinas/metabolismo , Epitelio Corneal/efectos de los fármacos , Receptores de Calcitriol/fisiología , Animales , Western Blotting , Calcio/metabolismo , Línea Celular , Conexina 26 , Conexina 30/metabolismo , Conexina 43/metabolismo , Epitelio Corneal/metabolismo , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Transducción de SeñalRESUMEN
Many antibiotics, chemotherapeutics, crop protection agents and food preservatives originate from molecules produced by bacteria, fungi or plants. In recent years, genome mining methodologies have been widely adopted to identify and characterize the biosynthetic gene clusters encoding the production of such compounds. Since 2011, the 'antibiotics and secondary metabolite analysis shell-antiSMASH' has assisted researchers in efficiently performing this, both as a web server and a standalone tool. Here, we present the thoroughly updated antiSMASH version 4, which adds several novel features, including prediction of gene cluster boundaries using the ClusterFinder method or the newly integrated CASSIS algorithm, improved substrate specificity prediction for non-ribosomal peptide synthetase adenylation domains based on the new SANDPUMA algorithm, improved predictions for terpene and ribosomally synthesized and post-translationally modified peptides cluster products, reporting of sequence similarity to proteins encoded in experimentally characterized gene clusters on a per-protein basis and a domain-level alignment tool for comparative analysis of trans-AT polyketide synthase assembly line architectures. Additionally, several usability features have been updated and improved. Together, these improvements make antiSMASH up-to-date with the latest developments in natural product research and will further facilitate computational genome mining for the discovery of novel bioactive molecules.
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Metabolismo Secundario/genética , Programas Informáticos , Algoritmos , Antibacterianos/biosíntesis , Productos Biológicos/metabolismo , Vías Biosintéticas/genética , Codón , Genes , Internet , Péptido Sintasas/metabolismo , Péptidos/química , Péptidos/metabolismo , Sintasas Poliquetidas/química , Dominios Proteicos , Procesamiento Proteico-Postraduccional , Terpenos/químicaRESUMEN
"Click" type reactions represent the currently most prevalent postpolymerization strategy for the preparation of functional polymeric materials. Herein, a novel photoiniferter agent 4-(fluorosulfonyl)benzyl diethylcarbamodithioate (FSB-DECT) containing both dithiocarbamates and sulfonyl fluoride moieties is developed to act as both photoinitiator and click sulfur(VI)-fluoride exchange (SuFEx) agent. The photopolymerization behavior of FSB-DECT is demonstrated via standard photoiniferter-mediated polymerization for various types of monomer including N-isopropylacrylamide (NIPAAm), glycidyl methacrylate, and vinyl acetate (VAc). Gel permeation chromatography data show that the polymerization is relatively well controlled, with polydispersity indices of the product homopolymers in the range of 1.3-1.6. 1 H and 19 F NMR spectra and "reinitiated" photopolymerization indicate that the sulfonyl fluoride and diethyldithiocarbamyl groups remain at the respective ends of the homopolymer chains. Furthermore, using the sulfonyl fluoride end-functionalized poly(N-isopropylacrylamide) as a model polymer, the utility of the SuFEx reaction for efficient postpolymerization functionalization is demonstrated.
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Benzoatos/química , Química Clic/métodos , Ditiocarba/química , Fluoruros/química , Azufre/química , Acrilamidas/química , Cromatografía en Gel , Compuestos Epoxi/química , Metacrilatos/química , Procesos Fotoquímicos , Polimerizacion/efectos de la radiación , Polímeros/síntesis química , Polímeros/química , Ácidos Sulfínicos/química , Tiocarbamatos/química , Compuestos de Vinilo/químicaRESUMEN
Synthetic dosage lethality (SDL) denotes a genetic interaction between two genes whereby the underexpression of gene A combined with the overexpression of gene B is lethal. SDLs offer a promising way to kill cancer cells by inhibiting the activity of SDL partners of activated oncogenes in tumors, which are often difficult to target directly. As experimental genome-wide SDL screens are still scarce, here we introduce a network-level computational modeling framework that quantitatively predicts human SDLs in metabolism. For each enzyme pair (A, B) we systematically knock out the flux through A combined with a stepwise flux increase through B and search for pairs that reduce cellular growth more than when either enzyme is perturbed individually. The predictive signal of the emerging network of 12,000 SDLs is demonstrated in five different ways. (i) It can be successfully used to predict gene essentiality in shRNA cancer cell line screens. Moving to clinical tumors, we show that (ii) SDLs are significantly underrepresented in tumors. Furthermore, breast cancer tumors with SDLs active (iii) have smaller sizes and (iv) result in increased patient survival, indicating that activation of SDLs increases cancer vulnerability. Finally, (v) patient survival improves when multiple SDLs are present, pointing to a cumulative effect. This study lays the basis for quantitative identification of cancer SDLs in a model-based mechanistic manner. The approach presented can be used to identify SDLs in species and cell types in which "omics" data necessary for data-driven identification are missing.
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Dosificación de Gen/fisiología , Regulación Neoplásica de la Expresión Génica/fisiología , Genes Letales/genética , Redes y Vías Metabólicas/fisiología , Modelos Genéticos , Neoplasias/genética , Biología de Sistemas/métodos , Simulación por Computador , Genes Supresores de Tumor , Humanos , Redes y Vías Metabólicas/genética , Neoplasias/metabolismo , Oncogenes/genéticaRESUMEN
STATEMENT OF PROBLEM: Indirect composite resins (ICR) are promising alternatives as veneering materials for zirconia frameworks. The effects of core-to-dentin thickness ratio (C/Dtr) on the mechanical property of bilayered veneer ICR/yttria-tetragonal zirconia polycrystalline (Y-TZP) core disks have not been previously studied. PURPOSE: The purpose of this in vitro study was to assess the effects of C/Dtr on the biaxial flexural strength, reliability, and fracture mode of bilayered veneer ICR/ Y-TZP core disks. MATERIAL AND METHODS: A total of 180 bilayered 0.6-mm-thick composite resin disks in core material and C/Dtr of 2:1, 1:1, and 1:2 were tested with either core material placed up or placed down for piston-on-3-ball biaxial flexural strength. The mean biaxial flexural strength, Weibull modulus, and fracture mode were measured to evaluate the variation trend of the biaxial flexural strength, reliability, and fracture mode of the bilayered disks with various C/Dtr. One-way analysis of variance (ANOVA) and chi-square tests were used to evaluate the variation tendency of fracture mode with the C/Dtr or material placed down during testing (α=.05). Light microscopy was used to identify the fracture mode. RESULTS: The mean biaxial flexural strength and reliability improved with the increase in C/Dtr when specimens were tested with the core material either up and down, and depended on the materials that were placed down during testing. The rates of delamination, Hertzian cone cracks, subcritical radial cracks, and number of fracture fragments partially depended on the C/Dtr and the materials that were placed down during testing. CONCLUSION: The biaxial flexural strength, reliability, and fracture mode in bilayered structures of Y-TZP core and veneer ICR depend on both the C/Dtr and the material that was placed down during testing.
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Resinas Compuestas/uso terapéutico , Coronas con Frente Estético , Itrio/uso terapéutico , Circonio/uso terapéutico , Resinas Compuestas/normas , Fracaso de la Restauración Dental , Análisis del Estrés Dental , Dentina , Humanos , Técnicas In Vitro , Resistencia a la Tracción , Itrio/normas , Circonio/normasRESUMEN
OBJECTIVE: microRNA (miR)-328 has been reported to be implicated into tumorigenesis and tumor progression in human gliomas. However, there were controversial study results in relation to its expression pattern as well as functions in this disease. The aim of the current study was to determine the clinical significance of miR-328 expression in patients with gliomas and its effect in tumor cell malignant phenotypes. METHODS: Quantitative real-time PCR was performed to detect the expression levels of miR-328 in 116 glioma and 15 non-neoplastic brain tissues. Then, the correlations of miR-328 expression with selected clinicopathologic parameters and clinical outcome of glioma patients were statistically evaluated. Moreover, CCK-8 and transwell assays were performed to investigate the functions of miR-328 in cell proliferation, invasion and migration, respectively. RESULTS: Compared to non-neoplastic brain tissues, the expression levels of miR-328 were significantly downregulated in glioma tissues (p < 0.001). In addition, miR-328 downregulation was significantly associated with WHO grade (p < 0.001) and Karnofsky performance status score (p = 0.02). Moreover, glioma patients with low miR-328 expression exhibited markedly shorter overall survival than those with high expression (p < 0.001). Furthermore, functional assays in vitro system demonstrated that enforced expression of miR-328 could notably attenuate cell proliferation, invasion and migration of two glioma cell lines, including U251 and U87. CONCLUSIONS: Our data offer the convincing evidence that loss of miR-328 expression may stimulate advanced tumor progression and adverse outcome via promoting cellular proliferation and invasion. We propose a tumor suppressive role of miR-328 and its potential therapeutic value in human glioma.
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Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica/genética , Glioma/genética , MicroARNs/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Transportadoras de Casetes de Unión a ATP/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/mortalidad , Línea Celular Tumoral , Movimiento Celular/genética , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Proteínas de Neoplasias/metabolismo , Estudios Retrospectivos , Análisis de Supervivencia , Adulto JovenRESUMEN
Derived from mature adipocytes, dedifferentiated fat (DFAT) cells represent a special group of multipotent cells. However, their phenotype and cellular nature remain unclear. Our study found that human DFAT cells adopted perivascular characteristics and behaviors. Flow cytometry and immunofluorescent staining revealed that human DFAT cells positively expressed markers highly related to perivascular cell lineages, such as CD140b, NG2 and desmin, but were negative for common endothelial markers, including CD31, CD34, and CD309. Furthermore, DFAT cells displayed vascular network formation ability in Matrigel, and they noticeably promoted and stabilized the vessel structures formed by human umbilical vascular endothelial cells (HUVECs) in vitro. These results provide novel evidence on the pericyte nature of human DFAT cells, further supporting the recent model for the perivascular origin of adult stem cells, in which tissue-specific progenitor cells in mesenchymal tissues associate with blood vessels, exhibiting perivascular characteristics and functions.
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Adipocitos/citología , Células Madre Adultas/citología , Desdiferenciación Celular , Células Madre Multipotentes/citología , Adipocitos/metabolismo , Adulto , Células Madre Adultas/metabolismo , Antígenos/metabolismo , Antígenos CD/metabolismo , Antígeno CD146/metabolismo , Células Cultivadas , Técnicas de Cocultivo , Células Endoteliales de la Vena Umbilical Humana , Humanos , Células Madre Multipotentes/metabolismo , Neovascularización Fisiológica , Fenotipo , Proteoglicanos/metabolismo , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismoRESUMEN
AIM: To study the effects of static magnetic fields (SMF) on the electrophysiological properties of voltage-gated sodium and calcium channels on trigeminal ganglion (TRG) neurons. METHODS: Acutely dissociated TRG neurons of neonatal SD rats were exposed to 125-mT and 12.5-mT SMF in exposure devices and whole-cell patch-clamp recordings were carried out to observe the changes of voltage-gated sodium channels (VGSC) and calcium channels (VGCC) currents, while laser scanning confocal microscopy was used to detect intracellular free Ca(2+) concentration in TRG neurons, respectively. RESULTS: (1) No obvious change of current-voltage (I-V) relationship and the peak current densities of VGSC and VGCC currents were found when TRG neurons were exposed to 125-mT and 12.5-mT SMF. However, the activation threshold, inactivation threshold and velocity of the channel currents above were significantly altered by 125-mT and 12.5-mT SMF. (2) The fluctuation of intracellular free Ca(2+) concentration within TRG neurons were slowed by 125-mT and 12.5-mT SMF. When SMF was removed, the Ca(2+) concentration level showed partial recovery in the TRG neurons previously exposed by 125-mT SMF, while there was a full recovery found in 12.5-mT-SMF-exposed neurons. CONCLUSIONS: Moderate-intensity SMF could affect the electrophysiological characteristics of VGCS and VGCC by altering their activation and inactivation threshold and velocity. The fluctuations of intracellular free Ca(2+) caused by SMF exposure were not permanent in TRG neurons.