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Plant architecture is a major motif of plant diversity, and shoot branching patterns primarily determine the aerial architecture of plants. In this study, we identified an inbred pepper line with fewer lateral branches, 20C1734, which was free of lateral branches at the middle and upper nodes of the main stem with smooth and flat leaf axils. Successive leaf axil sections confirmed that in normal pepper plants, for either node n, Pn (Primordium n) < 1 cm and Pn+1 < 1 cm were the critical periods between the identification of axillary meristems and the establishment of the region, whereas Pn+3 < 1 cm was fully developed and formed a completely new organ. In 20C1734, the normal axillary meristematic tissue region establishment and meristematic cell identity confirmation could not be performed on the axils without axillary buds. Comparative transcriptome analysis revealed that "auxin-activated signaling pathway", "response to auxin", "response to abscisic acid", "auxin biosynthetic process", and the biosynthesis of the terms/pathways, such as "secondary metabolites", were differentially enriched in different types of leaf axils at critical periods of axillary meristem development. The accuracy of RNA-seq was verified using RT-PCR for some genes in the pathway. Several differentially expressed genes (DEGs) related to endogenous phytohormones were targeted, including several genes of the PINs family. The endogenous hormone assay showed extremely high levels of IAA and ABA in leaf axils without axillary buds. ABA content in particular was unusually high. At the same time, there is no regular change in IAA level in this type of leaf axils (normal leaf axils will be accompanied by AM formation and IAA content will be low). Based on this, we speculated that the contents of endogenous hormones IAA and ABA in 20C1734 plant increased sharply, which led to the abnormal expression of genes in related pathways, which affected the formation of Ams in leaf axils in the middle and late vegetative growth period, and finally, nodes without axillary buds and side branches appeared.
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Alimentos , Meristema , Meristema/genética , Ácido Abscísico , Pinos Ortopédicos , Ácidos IndolacéticosRESUMO
In the present work, mesoporous silica spheres-doping CuO (CuO/MSS) was prepared via a facile hydrothermal method. It acted as a peroxydisulfate (PDS) activator for the removal of bisphenol A (BPA). X-Ray diffraction (XRD), transmission electron microscope (TEM), scanning electron microscope (SEM), and energy dispersive X-ray spectroscopy (EDS) showed that CuO was successfully synthesized and silica spheres were doped in CuO. Nitrogen sorption isotherm showed that CuO/MSS, which had a high specific surface area and a narrow pore size distribution, exhibited a mesoporous structure. The effect of initial pH, PDS dosage, catalyst amount, and activation temperature was assessed. A removal efficiency of over 80% was observed after five consecutive cycles, suggesting the superior stability of the catalyst. X-ray photoelectron spectroscopy (XPS), radical quenching experiments, and electrochemical evaluation showed that BPA removal was dominated by the electron transfer among PDS, BPA, and the surface of CuO/MSS (non-radical pathway), while SO4·- and OH· radicals had a minor contribution (radical pathway). In addition, the degradation pathways of BPA were proposed according to the intermediates. Overall, this study indicates that CuO/MSS is a promising effective PDS activator to address the drawbacks of the classical Fenton process.
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Compostos Benzidrílicos , Dióxido de Silício , Cobre , FenóisRESUMO
The bluetongue virus (BTV) NS1 protein is one of the major proteins synthesized during BTV infection and is responsible for the generation of virus-specific tubules. Although some functional and structural studies on the BTV NS1 protein have been reported, there have been no reports describing the linear B-cell epitopes recognized by humoral immune responses published to date. In this study, 25 BTV12 NS1-reactive monoclonal antibodies (MAbs) and polyclonal antisera (polyclonal antibodies, PAbs) were generated and analyzed. We identified 14 linear NS1 epitopes recognized by the PAbs and MAbs using NS1-derived peptides in an enzyme-linked immunosorbent assay. Moreover, we predicted 23 linear B-cell epitopes using the ABCpred online server which employs an artificial neural network. Analysis of the predicted and identified epitopes of NS1 demonstrated the feasibility of B-cell epitope prediction. Sequence alignments indicated that the epitopes recognized by MAbs are highly conserved among BTV serotypes, but not among the other members of the genus Orbivirus, such as the African horse sickness virus (AHSV), epizootic hemorrhagic disease virus (EHDV), and Chuzan disease virus (CV). Importantly, we identified specific MAbs that recognized all BTV serotypes tested as well as MAbs that recognized only BTV12, suggesting that these NS1-specific MAbs could serve as a basis for BTV diagnostic approaches. The generation and identification of NS1 protein epitopes will provide the foundation for further studies about the function and structure of NS1 and novel epitope-based vaccines.
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Vírus Bluetongue/imunologia , Bluetongue/virologia , Epitopos de Linfócito B/química , Proteínas não Estruturais Virais/química , Sequência de Aminoácidos , Animais , Anticorpos/análise , Anticorpos/imunologia , Vírus Bluetongue/química , Vírus Bluetongue/genética , Linhagem Celular , Cricetinae , Mapeamento de Epitopos , Epitopos de Linfócito B/genética , Epitopos de Linfócito B/imunologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Modelos Moleculares , Dados de Sequência Molecular , Alinhamento de Sequência , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/imunologiaRESUMO
The Eastern equine encephalitis virus (EEEV) E2 protein is one of the main targets of the protective immune response against EEEV. Although some efforts have done to elaborate the structure and immune molecular basis of Alphaviruses E2 protein, the published data of EEEV E2 are limited. Preparation of EEEV E2 protein-specific antibodies and define MAbs-binding epitopes on E2 protein will be conductive to the antibody-based prophylactic and therapeutic and to the study on structure and function of EEEV E2 protein. In this study, 51 EEEV E2 protein-reactive monoclonal antibodies (MAbs) and antisera (polyclonal antibodies, PAbs) were prepared and characterized. By pepscan with MAbs and PAbs using enzyme-linked immunosorbent assay, we defined 18 murine linear B-cell epitopes. Seven peptide epitopes were recognized by both MAbs and PAbs, nine epitopes were only recognized by PAbs, and two epitopes were only recognized by MAbs. Among the epitopes recognized by MAbs, seven epitopes were found only in EEEV and two epitopes were found both in EEEV and Venezuelan equine encephalitis virus (VEEV). Four of the EEEV antigenic complex-specific epitopes were commonly held by EEEV subtypes I/II/III/IV (1-16aa, 248-259aa, 271-286aa, 321-336aa probably located in E2 domain A, domain B, domain C, domain C, respectively). The remaining three epitopes were EEEV type-specific epitopes: a subtype I-specific epitope at amino acids 108-119 (domain A), a subtype I/IV-specific epitope at amino acids 211-226 (domain B) and a subtype I/II/III-specific epitope at amino acids 231-246 (domain B). The two common epitopes of EEEV and VEEV were located at amino acids 131-146 and 241-256 (domain B). The generation of EEEV E2-specific MAbs with defined specificities and binding epitopes will inform the development of differential diagnostic approaches and structure study for EEEV and associated alphaviruses.
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Vírus da Encefalite Equina do Leste/imunologia , Encefalomielite Equina/virologia , Epitopos de Linfócito B/imunologia , Proteínas do Envelope Viral/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/imunologia , Vírus da Encefalite Equina do Leste/química , Vírus da Encefalite Equina do Leste/classificação , Vírus da Encefalite Equina do Leste/genética , Vírus da Encefalite Equina Venezuelana/química , Vírus da Encefalite Equina Venezuelana/classificação , Vírus da Encefalite Equina Venezuelana/genética , Vírus da Encefalite Equina Venezuelana/imunologia , Encefalomielite Equina/imunologia , Mapeamento de Epitopos , Epitopos de Linfócito B/química , Epitopos de Linfócito B/genética , Humanos , Camundongos , Especificidade da Espécie , Spodoptera , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/genéticaRESUMO
BACKGROUND: Treating marginalized populations with HCV infection for elimination is faced with the challenge for the integration of HCV screening service offered for patients often moving across multiple settings. We envisaged a novel collaborative care approach to identify to what extent HCV patients overlapped between and within these multiple institutions and reported the findings of treatment coverage of these marginalized populations after HCV care cascades. METHODS: We enrolled 7765 patients residing in the Changhua County, Taiwan offered with HCV screening from correctional institutions, HIV clinics, methadone clinics, and the existing HIV surveillance program (four subgroups including police-arrested people, probationers, non-injection drug user, and high-risk behavior people) between 2019 and 2020. The collaborative care and information were integrated through a teamwork of gastroenterologists, psychologists, infectious disease specialists, and nursing coordinators under the auspices of local health authority. RESULTS: The overall participation rate in HCV screening was 92.65% (7194/7765). The prevalence rate was the highest in methadone clinics (90.17%) followed by correctional institutions (37.67%), HIV clinics (34.60%), and the surveillance program (18.14%). We found 25.41% (77/303) of methadone clinic patients, 17.65% (129/731) of HIV clinic patients, and various proportions for 44.09% (41/93) of deferred prosecuted or probationers under surveillance program were also recruited into other settings. Individuals' patient flow within setting was more frequent than that between setting. After calibrating the overlap of patient flow, a total of 1700 anti-HCV positives out of 4074 after screening were traced with available follow-up information to complete 92.52% treatment coverage of 1177 RNA-positives (77.23%) diagnosed from 1524 undergoing RNA testing with similar findings across multiple settings. CONCLUSION: A new collaborative integrated care was adopted for elucidating patient flow between and within multiple settings in order to calibrate the accurate demand for HCV care cascades and enhance HCV treatment coverage in marginalized populations.
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Infecções por HIV , Hepatite C , Abuso de Substâncias por Via Intravenosa , Humanos , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/epidemiologia , Abuso de Substâncias por Via Intravenosa/tratamento farmacológico , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Hepatite C/prevenção & controle , Hepacivirus , Metadona/uso terapêutico , Antivirais/uso terapêuticoRESUMO
Due to the present drought events and dynamics of vegetation, the circumstances in mainland China could become even more serious. Therefore, we study the impact of drought on vegetation trends in mainland China, with the aim of discovering the temporal and spatial differences in vegetation dynamics caused by seasonal drought. Our method is based on the use of data from the AVHRR Normalized Difference Vegetation Index (NDVI) from 1983 to 2016 and temperature and precipitation data from Modern Era Retrospective Analysis for Research and Applications (NASA's MERRA). Due to the sparse vegetation and low drought, NDVI is the most useful for describing drought conditions in mainland China. The NDVI, TCI, VHI, NVSWI, VCI, TVDI, and NAP from April to October increased rapidly, while the NDVI, TCI, VHI, NVSWI, NAP, TVDI, and VCI are stable every month in September, improve again in October, and then show in December a downward trend. The NDVI, TCI, VHI, NVSWI, NAP, TVDI, and VCI monthly values indicate that mainland China suffered from severe drought in 1984 and 1993, which lasted until 2007, which were the most drought years. For monitoring drought in mainland China, the NDVI, TVDI, NAP, VCI, and NVSWI values were selected as a tool for reporting drought events during different growing seasons. The seasonal values of TVDI, NDVI, NAP, NVSWI, and VCI confirmed that mainland China suffered from severe drought in 1984, 1993, and 2007 and led the durations of severe drought. Spatial correlation is generated between NDVI, TCI, VHI, NVSWI, NAP, TVDI, and VCI. The correlation between NDVI, TCI, VHI, NAP, and VCI showed a significantly positive correlation while significantly negative correlation between NVSWI and TVDI, TVDI and VHI, which showed a good indication for the assessment of drought, especially for the agricultural regions of mainland China. This shows that the positive sign to support NAP, NVSWI, and TVDI is a good monitoring of the drought indices. During the summer, it appears that compared to the southeastern part of mainland China, drought is more likely to occur in the northwestern areas. There is no doubt that these drought indices are comprehensive indicators of monitoring drought events in mainland China.
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Mudança Climática , Secas , China , Monitoramento Ambiental , Estudos Retrospectivos , Estações do Ano , TemperaturaRESUMO
OBJECTIVES: To investigate the association of the baseline New Chinese Diabetes Risk Score (NCDRS) with metabolic syndrome (MetS) risk and to evaluate the power of the baseline NCDRS to predict MetS based on the rural Chinese cohort study. METHODS: Study participants were classified by baseline quartiles of NCDRS by gender. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of MetS according to different diagnostic criteria. The receiver operating characteristic curve (ROC) and area under the ROC curve (AUC) were used to evaluate the power of the baseline NCDRS for predicting MetS according to different diagnostic criteria. RESULTS: We included 7,133 participants, and 1,651 MetS cases were identified after 6 years follow-up. After adjusting for multivariable confounding factors and with NCDRS quartile 1 as the reference, with quartile 4, the risk of MetS was increased for all participants, men and women: ORs (95% CIs) 4.03 (3.23-5.02), 3.59 (2.56-5.05) and 5.71 (4.23-7.70), respectively. Similar results were found on sensitivity analysis. The baseline NCDRS was a good predictor of MetS for all participants, men and women with MetS defined according to the diagnostic criteria of the Chinese Joint Committee on the Development of Guidelines for the Prevention and Treatment of Dyslipidemia in Adults (JCDCG). CONCLUSIONS: Our study, based on the cohort study, found that the baseline NCDRS was positively associated with risk of MetS. Furthermore, our study might provide suggestions for developing a useful and inexpensive tool for predicting MetS in the Chinese population.
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Diabetes Mellitus , Síndrome Metabólica , Adulto , China/epidemiologia , Estudos de Coortes , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Curva ROC , Fatores de RiscoRESUMO
OBJECTIVE: (1) To evaluate the value of CT-guided microcoil implantation for localizing pulmonary ground-glass nodules (GGNs) before video-assisted thoracoscopic surgery (VATS). (2) To evaluate the feasibility, safety and accuracy of cephalic-caudal oblique approach for lesions difficult to access on axial images owing to overlying bony structures, large vessels or interlober fissures. METHODS: From June 2016 to March 2019, all patients with GGNs resected by VATS after marking using CT-guided microcoil implantation in China-Japan friendship hospital were enrolled and clinical and imaging data were retrospectively analyzed. According to the microcoil marked path, the GGNs were divided into cephalic-caudal oblique group (oblique group) and non-oblique group. The success rate of marking, the time required for marking and the incidence of complications between the two groups were compared. RESULTS: 258 GGNs from 215 consecutive patients were included in this study. The diameter of GGNs was 1.22 ± 0.50 cm, and the shortest distance from GGNs to the pleura was 1.56 ± 1.09 cm. All 258 GGNs were successfully resected by VATS under the guidance of implanted microcoils, and no case was converted to thoracotomy. During CT-guided microcoil implantation, cephalic- caudal oblique approach was taken in 56 GGNs (oblique group) to avoid bone, interlobar fissure and blood vessels. The time required for marking was significantly longer for oblique group compared with non-oblique group (16.6 ± 2.4 vs. 13.1 ± 1.9 min, p<0.01). No significant differences in the success rate of marking (94.6% vs 91.6%), the incidence of pneumothorax (19.6% vs 17.8%), the bleeding rate (10.7% vs 8.9%), and the hemoptysis rate (1.8% vs 1.5%) were observed between the two groups. CONCLUSION: CT-guided microcoil implantation can effectively guide VATS to resect GGNs. For GGNs difficult to access on axial images, CT-guided cephalic-caudal oblique approach is feasible, safe, and accurate. ADVANCES IN KNOWLEDGE: CT-guided microcoil implantation can effectively guide VATS to resect GGNs. The marked path with cephalic-caudal obliquity can effectively avoid bone, interlobar fissure and blood vessels, successfully mark GGNs difficult to access on axial images, while keeping the distance from the pleura to the lesion on the marked path as short as possible at the same time.
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Neoplasias Pulmonares/cirurgia , Nódulos Pulmonares Múltiplos/cirurgia , Cirurgia Torácica Vídeoassistida/métodos , Estudos de Viabilidade , Feminino , Marcadores Fiduciais , Humanos , Masculino , Pessoa de Meia-Idade , Implantação de Prótese , Radiografia Intervencionista , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
We developed and validated a sensitive and low sample volume liquid chromatographic-mass spectrometric (LC-MS) method for determination of Promethazine hydrochloride in human plasma (0.5 ml) or urine (0.1 ml). The lower limit of quantification in human plasma and urine was 1.00 ng/ml. The inter- and intra-day precisions (CV %) in both plasma and urine were lower than 10%, the mean method accuracies and recoveries from spiked plasma samples at three concentrations were more than 97%. The developed method was successfully applied to determine Promethazine hydrochloride in human plasma and urine, and proved suitable to clinical pharmacokinetic study.
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Cromatografia Líquida de Alta Pressão/métodos , Antagonistas dos Receptores Histamínicos H1/farmacocinética , Espectrometria de Massas/métodos , Prometazina/farmacocinética , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Humanos , Prometazina/administração & dosagem , Reprodutibilidade dos Testes , Tramadol/administração & dosagem , Tramadol/farmacocinéticaRESUMO
A sensitive and selective liquid chromatography-tandem mass spectrometric (LC-MS) method was developed and validated for the determination of Tramadol in human plasma and urine. The analyte was separated on a Diamonsil C18 column with ammonium acetate (5 mmol x L(-1))-methanol (50:50,v:v) adjusted PH by caustic soda at a flow rate of 0.8 ml min(-1), and analyzed by mass spectrometry is in positive ion mode. The ion mass spectrum of m/z were 264.1 for Tramadol and 248.0 for Tinidazole (I.S.), respectively. The weighted (1/x2) calibration curve was linear over plasma concentration range 1.00-400.00 ng/ml and urine concentration range 0.01-16.00 microg/ml, with a correlation coefficient (r) of 0.9995 and 0.9997, respectively. The lower limit of quantification in human plasma was 1.00 ng/ml. The inter-and intra-day precisions (CV%) in both plasma and urine were lower than 10%, the mean method accuracies and recoveries from spiked plasma samples at three concentrations ranged from 98.2 to 100.1% and 61.6 to 62.9%, respectively. The developed method was successfully applied to determine Tramadol in human plasma and urine, and provided suitable profiles for clinical pharmacokinetic study of Tramadol.
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Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas/métodos , Tramadol/farmacocinética , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/farmacocinética , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Humanos , Prometazina/administração & dosagem , Prometazina/farmacocinética , Reprodutibilidade dos Testes , Tramadol/administração & dosagemRESUMO
The pharmacokinetics of Tramadol and Promethazine after a single dose of 40, 80 and 120 mg intramuscular injecting CTHI was evaluated in healthy volunteers. Physical exam, vital signs, clinical laboratory tests and electrocardiogram measurements were monitored to assess the safety and tolerance of the drug. The plasma levels of Tramadol and Promethazine in serial samples were measured by a validated HPLC-MS method. No subject showed any drug-related clinically significant changes on physical examination, vital signs or laboratory tests.
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Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas/métodos , Prometazina/farmacocinética , Tramadol/farmacocinética , Adulto , China , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Eletrocardiografia , Feminino , Humanos , Injeções Intramusculares , Masculino , Prometazina/administração & dosagem , Prometazina/efeitos adversos , Estudos Prospectivos , Tramadol/administração & dosagem , Tramadol/efeitos adversos , Adulto JovemRESUMO
A remarkably large species difference in cinchonidine oxidation activity catalyzed by aldehyde oxidase (AO) has been known, in particular between rabbit and monkey. As the first step in clarifying the phenomenon from the view point of structures of the active site, we attempted to construct an expression system of rabbit AO cDNA. The nucleotide sequences of cloned full-length rabbit AO cDNA were determined and confirmed to agree completely with those of genome DNA. The expression system in Escherichia coli was constructed in reference to the previously established method for monkey AO. Both expressed rabbit and monkey AO proteins correctly reproduced the remarkable species differences observed in their liver cytosols towards cinchonidine and methotrexate. Namely, the expressed rabbit AO protein showed extremely high activities than did that of monkey AO. A difference in the structure of the active site might be responsible for the substrate-dependent species difference towards the relatively bulky molecules of cinchonidine and methotrexate. The use of molecular biology techniques will be very useful to verify the hypothesis.
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Aldeído Oxidase/genética , DNA Complementar , Expressão Gênica , Aldeído Oxidase/metabolismo , Animais , Sequência de Bases , Alcaloides de Cinchona/metabolismo , Citosol/enzimologia , Escherichia coli , Fígado/enzimologia , Macaca fascicularis , Masculino , Metotrexato/metabolismo , Coelhos , Ratos , Ratos Wistar , Análise de Sequência de DNA , Especificidade da EspécieRESUMO
PURPOSE: This prospective, single-arm, open-label, 8-week, multicenter study investigated the effectiveness of switching from immediate-release methylphenidate (IR-MPH) to osmotic controlled-release methylphenidate (OROS-MPH) in patients with attention-deficit/hyperactivity disorder (ADHD). PATIENTS AND METHODS: Overall, 296 patients with ADHD (mean age: 9.5 years) already on IR-MPH treatment were enrolled. Upon enrollment, a flexible dose of OROS-MPH was administered, replacing IR-MPH. Patients were assessed at baseline and weeks 2, 4, and 8 using the Swanson, Nolan, and Pelham version IV scale (SNAP-IV) and the Clinical Global Impression for ADHD symptoms. The Social Adjustment Inventory for Children and Adolescents assessed social functions, and the Chinese Health Questionnaire (CHQ) and Family Adaptation, Partnership, Growth, Affection, and Resolve evaluated parental and family functions. RESULTS: Switching from IR-MPH to OROS-MPH yielded significant improvements in all ADHD symptoms, as rated by parents, teachers (SNAP-IV), and study investigators (Clinical Global Impression). CHQ scores and all Social Adjustment Inventory for Children and Adolescents subscores except spare time scores improved significantly. Patients with poor IR-MPH adherence had greater improvements in teacher-rated SNAP-IV and mothers' mental health (CHQ) after switching. CONCLUSION: Switching from IR-MPH to OROS-MPH improved patients' behavioral ADHD symptoms and social adjustment, and mental health of patients' mothers. This was most evident in patients who previously exhibited poor IR-MPH adherence.
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Objectives Hypofunction of NMDA receptor is implicated in the pathophysiology, particularly cognitive impairment, of schizophrenia. Sarcosine, a glycine transporter I (GlyT-1) inhibitor, and sodium benzoate, a d-amino acid oxidase (DAAO) inhibitor, can both enhance NMDA receptor-mediated neurotransmission. We proposed simultaneously inhibiting DAAO and GlyT-1 may be more effective than inhibition of either in improving the cognitive and global functioning of schizophrenia patients. Methods This study compared add-on sarcosine (2 g/day) plus benzoate (1 g/day) vs. sarcosine (2 g/day) for the clinical symptoms, as well as the cognitive and global functioning, of chronic schizophrenia patients in a 12-week, double-blind, randomised, placebo-controlled trial. Participants were measured with the Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale every 3 weeks. Seven cognitive domains, recommended by the Measurement and Treatment Research to Improve Cognition in Schizophrenia Committee, were measured at weeks 0 and 12. Results Adjunctive sarcosine plus benzoate, but not sarcosine alone, improved the cognitive and global functioning of patients with schizophrenia, even when their clinical symptoms had not improved. Conclusions This finding suggests N-methyl-d-aspartate receptor-enhancement therapy can improve the cognitive function of patients with schizophrenia, further indicating this pro-cognitive effect can be primary without improvement in clinical symptoms.
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Antipsicóticos/administração & dosagem , Benzoatos/administração & dosagem , Cognição/efeitos dos fármacos , Sarcosina/administração & dosagem , Esquizofrenia/tratamento farmacológico , Adulto , Doenças dos Gânglios da Base/etiologia , Doença Crônica , D-Aminoácido Oxidase/antagonistas & inibidores , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Proteínas da Membrana Plasmática de Transporte de Glicina/antagonistas & inibidores , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , TaiwanRESUMO
NONCODE is a comprehensive database that aims to present the most complete collection and annotation of non-coding RNAs, especially long non-coding RNAs (lncRNA genes), and thus NONCODE is essential to modern biological and medical research. Scientists are producing a flood of new data from which new lncRNA genes and lncRNA-disease relationships are continually being identified. NONCODE assimilates such information from a wide variety of sources including published articles, RNA-seq data, micro-array data and databases on genetic variation (dbSNP) and genome-wide associations (GWAS). NONCODE organizes all this information and makes it freely available to the public via the Internet. The NONCODE protocol provides step-by-step instructions on how to browse and search lncRNA information such as sequence, expression, and disease relationships, how to use the tools for functional prediction, species conservation assays, blast analysis, identifier conversion, and, finally, how to submit sequences to identify lncRNA genes. As of Dec 2016, NONCODE has cataloged 487,851 lncRNA genes sequenced from 16 species. © 2017 by John Wiley & Sons, Inc.
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Biotecnologia/métodos , Bases de Dados de Ácidos Nucleicos , RNA Longo não Codificante/genética , InternetRESUMO
OBJECTIVE: To study the treatmaient of non-small cell lung cancer, we established the HU-Prim allograft transplantation tumor model. METHODS: The fresh tumor samples were transplanted in the right scapular subcutaneous layer of the severe combined immunodeficient Non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. The pathological features of the tumors were observed. Nonnecrotic tissue was inoculated subcutaneously into the right axillary. When the tumor in burdened rat grew approximately 100 mm3, according to the tumor size all the animals were divided into the following four groups, eight rats in each group:solvent control group, gefitinib group (100 mg/kg), erlotinib group (50 mg/kg), afatinib group (20 mg/kg). Aniamals were treated with drugs by intragastric (i.g.) administrated, once daily, for consecutively 14 days. Measure the tumor size 2-3 times every week. RESULTS: HuPrime1-NSCLC mutant sensitive xenograft model research data showed that reversible tyrosine kinase inhibitors gefitinib, erlotinib and irreversible tyrosine kinase inhibitor afatinib could effectively inhibit tumor growth in EGFR positive NSCLC allografts model. The pharmacodynamic activity of irreversible inhibitor was better than that of the reversible inhibitor. Specimens from clinical anthropogenic tumor retain characteristics of the human primary malignancy, histopathology, biological characteristics, and tumor markers, etc., which can more accurately reflect the characteristics of the tumor and the impact of interventions. CONCLUSIONS: The model is not only a good antitumor drug experimental platform, but also a new evaluation tool of individualized medication.
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Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Afatinib , Animais , Linhagem Celular Tumoral , Cloridrato de Erlotinib/farmacologia , Gefitinibe , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Quinazolinas/farmacologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
This study aims to evaluate the endocrine-disrupting effect of dioxin congeners on adrenal steroid hormones in mother-child pairs. In our previous study, we found that cortisol and cortisone levels were higher in the blood and the saliva of mothers living in a dioxin hotspot area than in mothers from a non-exposed region in Vietnam. In this follow-up study, we determined the salivary steroid hormone levels in 49 and 55 three-year-old children of these mothers in the hotspot and non-exposed region, respectively. Steroid hormones were determined by liquid chromatography-tandem mass spectrometry, and dioxin in the maternal breast milk was determined by gas chromatography-mass spectrometry. Dioxin levels in the breast milk of mothers from the hotspot (median total toxic equivalents polychlorinated dibenzodioxins/polychlorinated dibenzofurans; (TEQ PCDD/Fs) of 11pg/g lipid) were three to four times higher than those of mothers in the non-exposed region (median TEQ PCDD/Fs of 3.07pg/g lipid). Salivary dehydroepiandrosterone (DHEA) levels in children were found to be significantly lower in the hotspot than in the non-exposed region, while cortisol and cortisone levels were not different between the two regions. Highly chlorinated dioxin congeners, such as octacholorodibenzodioxin (OCDD), 1,2,3,4,6,7,8-heptacholorodibenzodioxin (HpCDD) and 1,2,3,4 (or 6), 7,8-hexachlorodibenzodioxin Hx(CDD), showed stronger inverse associations with the children's salivary DHEA than other lowly chlorinated dioxin congeners. Glucocorticoid levels in the mothers exhibited a significantly positive correlation with OCDD and HpCDD/F (polychlorinated dibenzofurans). In conclusion, highly chlorinated dioxin congeners are more strongly correlated with endocrine-disrupting effects on adrenal hormones, resulting in high cortisol levels in the mothers and low DHEA levels in their three-year-old children.
Assuntos
Desidroepiandrosterona/metabolismo , Dioxinas/metabolismo , Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/metabolismo , Leite Humano/metabolismo , Criança , Dioxinas/análise , Exposição Ambiental/análise , Poluentes Ambientais/análise , Feminino , Seguimentos , Humanos , Exposição Materna/estatística & dados numéricos , Vietnã , Adulto JovemRESUMO
We determined polychlorinated dibenzodioxin (PCDD) and polychlorinated dibenzofuran (PCDF) levels in breast milk of 143 primiparae living around the three most dioxin-contaminated areas of Vietnam. The women sampled lived in the vicinity of former U.S. air bases at Bien Hoa (n=51), Phu Cat (n=23), and Da Nang (n=69), which are known as dioxin hotspots. Breast milk samples from Bien Hoa City, where residents live very close to the air base, showed high levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), with 18% of the samples containing >5 pgTCDD/g lipid. However, Phu Cat residents lived far from the air base and their samples showed lower TCDD levels, with none containing >5 pgTCDD/g lipid. In Da Nang, TCDD levels in mothers from Thanh Khe (close to the air base, n=43) were significantly higher than those in mothers from Son Tra (far from the air base, n=26), but not other PCDD and PCDF (PCDD/F) congeners. Although TCDD levels in Bien Hoa were the highest among these hotspots, levels of other PCDD/F congeners as well as the geometric mean concentration of total PCDD/F level in Bien Hoa (9.3 pg toxic equivalents [TEQ]/g lipid) were significantly lower than the level observed in Phu Cat (14.1 pgTEQ/g lipid), Thanh Khe (14.3 pgTEQ/g lipid), and Son Tra (13.9 pgTEQ/g lipid). Our findings indicated that residents living close to former U.S. air bases were exposed to elevated levels of TCDD, but not of other PCDD/F congeners.