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1.
Mol Cell ; 82(21): 4080-4098.e12, 2022 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-36272410

RESUMO

Growing evidence suggests prevalence of transcriptional condensates on chromatin, yet their mechanisms of formation and functional significance remain largely unclear. In human cancer, a series of mutations in the histone acetylation reader ENL create gain-of-function mutants with increased transcriptional activation ability. Here, we show that these mutations, clustered in ENL's structured acetyl-reading YEATS domain, trigger aberrant condensates at native genomic targets through multivalent homotypic and heterotypic interactions. Mechanistically, mutation-induced structural changes in the YEATS domain, ENL's two disordered regions of opposing charges, and the incorporation of extrinsic elongation factors are all required for ENL condensate formation. Extensive mutagenesis establishes condensate formation as a driver of oncogenic gene activation. Furthermore, expression of ENL mutants beyond the endogenous level leads to non-functional condensates. Our findings provide new mechanistic and functional insights into cancer-associated condensates and support condensate dysregulation as an oncogenic mechanism.


Assuntos
Neoplasias , Corpos Nucleares , Humanos , Domínios Proteicos , Cromatina/genética , Mutação , Neoplasias/genética
2.
Nature ; 577(7788): 121-126, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31853060

RESUMO

Modifications of histone proteins have essential roles in normal development and human disease. Recognition of modified histones by 'reader' proteins is a key mechanism that mediates the function of histone modifications, but how the dysregulation of these readers might contribute to disease remains poorly understood. We previously identified the ENL protein as a reader of histone acetylation via its YEATS domain, linking it to the expression of cancer-driving genes in acute leukaemia1. Recurrent hotspot mutations have been found in the ENL YEATS domain in Wilms tumour2,3, the most common type of paediatric kidney cancer. Here we show, using human and mouse cells, that these mutations impair cell-fate regulation by conferring gain-of-function in chromatin recruitment and transcriptional control. ENL mutants induce gene-expression changes that favour a premalignant cell fate, and, in an assay for nephrogenesis using murine cells, result in undifferentiated structures resembling those observed in human Wilms tumour. Mechanistically, although bound to largely similar genomic loci as the wild-type protein, ENL mutants exhibit increased occupancy at a subset of targets, leading to a marked increase in the recruitment and activity of transcription elongation machinery that enforces active transcription from target loci. Furthermore, ectopically expressed ENL mutants exhibit greater self-association and form discrete and dynamic nuclear puncta that are characteristic of biomolecular hubs consisting of local high concentrations of regulatory factors. Such mutation-driven ENL self-association is functionally linked to enhanced chromatin occupancy and gene activation. Collectively, our findings show that hotspot mutations in a chromatin-reader domain drive self-reinforced recruitment, derailing normal cell-fate control during development and leading to an oncogenic outcome.


Assuntos
Linhagem da Célula , Cromatina/genética , Proteínas de Ligação a DNA/metabolismo , Mutação com Ganho de Função , Fatores de Transcrição/metabolismo , Animais , Diferenciação Celular , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Células HEK293 , Humanos , Camundongos , Néfrons/metabolismo , Néfrons/patologia , Fatores de Transcrição/química , Fatores de Transcrição/genética
3.
Int J Audiol ; 63(3): 207-212, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36662150

RESUMO

OBJECTIVE: This exploratory study examined whether central auditory tests show differences between people living with HIV (PLWH) treated with two predominant antiretroviral drug therapy (ART) regimens. DESIGN: Cross-sectional. STUDY SAMPLE: 253 PLWH (mean age 39.8 years) from the Shanghai Public Health Clinical Centre, China. METHODS: The Hearing in Noise Test speech reception threshold (SRT) assessed central auditory function and the Montreal Cognitive Assessment (MoCA) assessed cognition. The relationship between ART regimen and SRT was evaluated with multivariable linear regression incorporating age, HIV duration, and peripheral hearing ability. Multivariable logistic regression was used to ascertain if SRT and ART regimen predicted MoCA impairment. RESULTS: The two predominant ART regimens differed by one drug (zidovudine or tenofovir). Participants taking the zidovudine-containing regimen had poorer SRT performance (p=.012) independent of age and hearing thresholds. MoCA scores did not differ between drug regimens, but a negative relationship was found between SRT and MoCA impairment (p=.048). CONCLUSIONS: ART regimens differed in their association with central auditory test performance likely reflecting neurocognitive changes in PLWH taking the zidovudine-containing regimen. Central auditory test performance also marginally predicted cognitive impairment, supporting further assessment of central auditory tests to detect neurocognitive deficits in PLWH.


Assuntos
Infecções por HIV , Percepção da Fala , Adulto , Humanos , Zidovudina/uso terapêutico , Estudos Transversais , China , Testes Auditivos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia
4.
Health Soc Work ; 49(1): 7-15, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38066681

RESUMO

Racial/ethnic minorities are underrepresented in hospice care in the United States, despite this being the standard of care for terminally ill individuals. Research indicates that location of services (e.g., rural vs. urban) plays a role in the differences in quality and quantity of services observed. However, the influences of neighborhood structural characteristics on quality of hospice services have not been explored. The purpose of this study was to explore the relationship between hospice neighborhood characteristics and caregiver-rated satisfaction with services in Florida. Data were derived from the Consumer Assessment of Healthcare Providers and Systems Hospice Survey and American Community Survey; ArcGIS was used to generate heat maps to provide visual representations. Findings showed that higher neighborhood immigrant density predicted lower family satisfaction with timely care, communication, spiritual support, and likelihood to recommend the agency services. The U.S. population is projected to continue to grow in its diversity, and thus understanding neighborhood characteristics associated with racial/ethnic minorities' perception of care quality are important for shaping care improvements.


Assuntos
Cuidados Paliativos na Terminalidade da Vida , Hospitais para Doentes Terminais , Humanos , Estados Unidos , Sistemas de Informação Geográfica , Pessoal de Saúde , Florida
5.
J Am Chem Soc ; 142(51): 21450-21459, 2020 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-33306911

RESUMO

YEATS domains are newly identified epigenetic "readers" of histone lysine acetylation (Kac) and crotonylation (Kcr). The malfunction of YEATS-Kac/Kcr interactions has been found to be involved in the pathogenesis of human diseases, such as cancer. These discoveries suggest that the YEATS domains are promising novel drug targets. We and others recently reported the development of YEATS domain inhibitors. Although these inhibitors have a general preference toward the AF9 and ENL YEATS domains, selective inhibitors targeting either YEATS domain are challenging to develop as these two proteins share a high structural similarity. In this study, we identified a proximal site outside the acyllysine-binding pocket that can differentiate AF9 YEATS from ENL YEATS. Combinatorial targeting of both the acyllysine pocket and this additional site by conformationally preorganized cyclopeptides enabled the selective inhibition of the AF9 YEATS domain. The most selective inhibitor, JYX-3, showed a 38-fold higher binding affinity toward AF9 YEATS over ENL YEATS. Further investigations indicated that JYX-3 could engage with AF9 in living cells, disrupt the YEATS-dependent chromatin recruitment of AF9, and suppress the transcription of AF9 target genes.


Assuntos
Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/química , Peptídeos Cíclicos/farmacologia , Acetilação , Sequência de Aminoácidos , Animais , Linhagem Celular , Cromatina/efeitos dos fármacos , Cromatina/metabolismo , Camundongos , Proteínas Nucleares/metabolismo , Peptídeos Cíclicos/química , Domínios Proteicos/efeitos dos fármacos
6.
J Med Virol ; 92(10): 1922-1931, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32297985

RESUMO

The aim of our study was to evaluate the therapeutic effect of antiviral drugs on coronavirus disease 2019 (COVID-19) pneumonia. Patients confirmed with COVID-19 pneumonia were enrolled and divided into seven groups according to the treatment option. Information including age, sex, and duration from illness onset to admission, clinical manifestations, and laboratory data at admission, and length of hospital stay were evaluated. The chest computed tomography (CT) imaging obtained at admission and after a 5-day treatment cycle were assessed. The clinical symptoms and laboratory tests at discharge were also assessed. At admission, no significant differences were found among the groups, including the duration from illness onset to admission, clinical symptoms, and main laboratory results. No significant differences were found among the groups in terms of the proportion of patients with pneumonia resolution (P = .151) after treatment or the length of hospital stay (P = .116). At discharge, 7 of 184 (4%) patients had a mild cough while their other symptoms had disappeared, and the proportion of patients with abnormal liver function and with increased leukocytes, neutrophils or erythrocyte sedimentation rate among the 184 patients were close to those at admission. According to the results, the inclusion of antiviral drugs in therapeutic regimens based on symptomatic treatment had no significant additional impact on the improvement in COVID-19 patients. In addition, the results of chest CT imaging, clinical manifestations, and laboratory tests at discharge were not completely consistent.


Assuntos
Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Pneumonia Viral/tratamento farmacológico , COVID-19/virologia , China , Feminino , Hospitalização , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/virologia , Estudos Retrospectivos , SARS-CoV-2/efeitos dos fármacos
7.
Molecules ; 23(8)2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30071672

RESUMO

Background: Allergic disease is a common clinical disease. Natural products provide an important source for a wide range of potential anti-allergic agents. This study was designed to evaluate the anti-allergic activities of the water-soluble polysaccharides extracted and purified from Saposhnikoviae Radix (SRPS). The composition and content of monosaccharides were determined to provide a material basis. Methods: An ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established to determine the composition and content of SRPS. 2,4-dinitrofluorobenzene (DNFB) induced a delayed-type hypersensitivity (DTH) mouse model orally administrated SRPS for seven consecutive days. Ear swelling, organ index, and serum IgE levels were observed to evaluate the anti-allergic activities. Results: The UPLC-MS/MS analysis showed that SRPS was consisted of eight monosaccharides including galacturonic acid, mannose, glucose, galactose, rhamnose, fucose, ribose, and arabinose with a relative molar ratio of 4.42%, 7.86%, 23.69%, 12.06%, 3.10%, 0.45%, 0.71%, and 47.70%, respectively. SRPS could effectively reduce ear swelling, a thymus index, and a serum IgE levels. Conclusions: The method was simple, rapid, sensitive, and reproducible, which could be used to analyze and determine the monosaccharide composition of SRPS. The vivo experiments demonstrated that SRPS may effectively inhibit development of DNFB-induced DTH. SRPS is a novel potential resource for natural anti-allergic drugs.


Assuntos
Apiaceae/química , Cromatografia Líquida de Alta Pressão/métodos , Monossacarídeos/análise , Espectrometria de Massas em Tandem/métodos , Animais , Antialérgicos/análise , Antialérgicos/uso terapêutico , Anti-Inflamatórios/análise , Anti-Inflamatórios/uso terapêutico , Dinitrofluorbenzeno/toxicidade , Modelos Animais de Doenças , Feminino , Hipersensibilidade Tardia/induzido quimicamente , Hipersensibilidade Tardia/tratamento farmacológico , Camundongos , Monossacarídeos/uso terapêutico , Polissacarídeos/análise , Polissacarídeos/uso terapêutico
8.
Heliyon ; 10(1): e23342, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38169709

RESUMO

Background: Only few studies have focused on the metabolite differences between asymptomatic neurocognitive impairment (ANI) and cognitively normal people living with HIV (PLWH). The current study aims to examine whether brain metabolisms in basal ganglia (BG) by magnetic resonance spectroscopy (MRS) were potential to discriminate ANI from cognitively normal PLWH. Methods: According to neuropsychological (NP) test, 80 PLWH (37.4 ± 10.2 years) were divided into ANI group (HIV-ANI, n = 31) and NP normal group (HIV-normal, n = 49). Brain metabolisms by MRS from right BG were compared between groups, including N-acetylaspartate and N-acetyl aspartylglutamate (tNAA), creatine and phosphocreatine (tCr), and choline-containing compounds (tCho). A total value of three metabolites were introduced. All brain metabolisms were evaluated as its percentage of total. Furthermore, correlations between MRS and NP and clinical measures were evaluated. A logistic regression model was applied, and the AUC values for the model and the continuous factors were compared using receiver operating curve (ROC) analysis. Results: Compared to HIV-normal group, tNAA/total was lower and tCr/total was higher in the HIV-ANI group (P < 0.05). Both tNAA/total and tCr/total values were correlated with NP score (P < 0.05), especially in verbal fluency, speed of information processing, learning, and recall (P < 0.05). The logistic model included BG-tCr/total, current CD4 and infection years of PLWH. The AUC value for the BG-tCr/total was 0.696 and was not significantly lower than that for logistic model (P < 0.01). Conclusion: The altered brain metabolites in the right BG were found in the ANI group compared to PLWH with normal cognition, and further associated with NP deficits. The current findings indicated that brain metabolites assessed by MRS has the potential to discriminate ANI from cognitively normal PLWH.

9.
Biomed Res Int ; 2022: 5066434, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35071595

RESUMO

Pseudomonas aeruginosa (PA), a Gram-negative bacterium, has a high detection rate in hospital-acquired infections. Recently, the frequent appearance of multidrug-resistant (MDR) PA strain with high morbidity and mortality rates has aggravated the difficulty in treating infectious diseases. Due to its multiple resistance mechanisms, the commonly used antibiotics have gradually become less effective. Qiguiyin decoction (QGYD) is a clinically experienced prescription of Chinese herbal medicine, and its combined application with antibiotics has been confirmed to be effective in the clinical treatment of MDR PA infection, which could be a promising strategy for the treatment of drug-resistant bacterial infections. However, the mechanism of QGYD restoring antibiotics susceptibility to MDR PA remains unclear. In the present study, we investigated the effects of QGYD and levofloxacin (LEV) singly or in combination on MDR PA-induced pneumonia rat models. Further analysis was carried out in the serum differential expression profiles of inflammatory cytokines by cytokine antibody array. Besides, the lung TLR4/MyD88/NF-κB signaling pathway was detected by RT-qPCR. Our results showed that based on the treatment of MDR PA-infected rat model with LEV, the combination of QGYD improved the general state and immune organ index. Furthermore, it moderately increased the expressions of proinflammatory cytokines including IL-1ß, IL-6, and TNF-α in the early stage of infection and decreased their release rapidly in the later stage, while regulated the same phase change of anti-inflammatory cytokine IL-10. In addition, the adhesion molecule ICAM-1 was significantly downregulated after QGYD combined with LEV treatment. Moreover, the mRNA expressions of TLR4, MyD88, NF-κB, and ICAM-1 were significantly downregulated. These results indicated that the mechanism of QGYD restoring LEV susceptibility to MDR PA was related to its regulation of inflammatory cytokines and the TLR4/MyD88/NF-κB signaling pathway, which provides theoretical support for the clinical application of QGYD combined with LEV therapy to MDR PA infection.


Assuntos
NF-kappa B , Infecções por Pseudomonas , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Citocinas/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/metabolismo , Ratos , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo
10.
Front Neurol ; 13: 909437, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35832184

RESUMO

Objective: Previous studies on HIV-infected (HIV+) individuals have revealed brain structural alterations underlying HIV-associated neurocognitive disorders. Most studies have adopted the widely used voxel-based morphological analysis of T1-weighted images or tracked-based analysis of diffusion tensor images. In this study, we investigated the HIV-related morphological changes using the deformation-based morphometry (DBM) analysis of T1-weighted images, which is another useful tool with high regional sensitivity. Materials and Methods: A total of 157 HIV+ (34.7 ± 8.5 years old) and 110 age-matched HIV-uninfected (HIV-) (33.7 ± 10.1 years old) men were recruited. All participants underwent neurocognitive assessments and brain scans, including high-resolution structural imaging and resting-state functional imaging. Structural alterations in HIV+ individuals were analyzed using DBM. Functional brain networks connected to the deformed regions were further investigated in a seed-based connectivity analysis. The correlations between imaging and cognitive or clinical measures were examined. Results: The DBM analysis revealed decreased values (i.e., tissue atrophy) in the bilateral frontal regions in the HIV+ group, including bilateral superior frontal gyrus, left middle frontal gyrus, and their neighboring white matter tract, superior corona radiata. The functional connectivity between the right superior frontal gyrus and the right inferior temporal region was enhanced in the HIV+ group, the connectivity strength of which was significantly correlated with the global deficit scores (r = 0.214, P = 0.034), and deficits in learning (r = 0.246, P = 0.014) and recall (r = 0.218, P = 0.031). Increased DBM indexes (i.e., tissue enlargement) of the right cerebellum were also observed in the HIV+ group. Conclusion: The current study revealed both gray and white matter volume changes in frontal regions and cerebellum in HIV+ individuals using DBM, complementing previous voxel-based morphological studies. Structural alterations were not limited to the local regions but were accompanied by disrupted functional connectivity between them and other relevant regions. Disruptions in neural networks were associated with cognitive performance, which may be related to HIV-associated neurocognitive disorders.

11.
Front Neurol ; 12: 757374, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35095719

RESUMO

PURPOSE: Neuroimaging elucidations have shown structural and functional brain alterations in HIV-infected (HIV+) individuals when compared to HIV-negative (HIV-) controls. However, HIV- groups used in previous studies were not specifically considered for sexual orientation, which also affects the brain structures and functions. The current study aimed to characterize the brain alterations associated with HIV infection while controlling for sexual orientation. METHODS: Forty-three HIV+ and 40 HIV- homosexual men (HoM) were recruited and underwent resting-state MRI scanning. Group differences in gray matter volume (GMV) were assessed using a voxel-based morphometry analysis. Brain regions with the altered GMV in the HIV+ HoM group were then taken as regions of interest in a seed-based analysis to identify altered functional connectivity. Furthermore, the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity values were compared between the two groups to evaluate the HIV-associated functional abnormalities in local brain regions. RESULTS: HIV+ HoM showed significantly increased GMV in the bilateral parahippocampal gyrus and amygdala, and decreased GMV in the right inferior cerebellum, compared with the HIV- HoM. The brain regions with increased GMV were hyper-connected with the left superior cerebellum, right lingual gyrus, and left precuneus in the HIV+ HoM. Moreover, the ALFF values of the right fusiform gyrus, and left parahippocampal gyrus were increased in the HIV+ HoM. The regional homogeneity values of the right anterior cingulate and paracingulate gyri, and left superior cerebellum were decreased in the HIV+ HoM. CONCLUSION: When the study population was restricted to HoM, HIV+ individuals exhibited structural alterations in the limbic system and cerebellum, and functional abnormalities in the limbic, cerebellum, and visual network. These findings complement the existing knowledge on the HIV-associated neurocognitive impairment from the previous neuroimaging studies by controlling for the potential confounding factor, sexual orientation. Future studies on brain alternations with the exclusion of related factors like sexual orientation are needed to understand the impact of HIV infection on neurocognitive function more accurately.

13.
Structure ; 28(1): 111-118.e3, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31711754

RESUMO

The Saccharomyces cerevisiae RSC (Remodel the Structure of Chromatin) complex is a chromatin-remodeling complex and plays essential roles in transcription regulation and DNA repair. The acetylation of H3 Lysine14 (H3K14Ac) enhances the RSC retention on nucleosomes and increases the remodeling activity of RSC. However, which RSC component recognizes H3K14Ac remains unclear. Here, we discovered that the bromodomain of the catalytic subunit Sth1 (Sth1BD) possessed the strongest affinity to H3K14Ac among all RSC bromodomains. The Sth1BD specifically recognized the K(Ac)ΦΦR motif (Φ stands for any hydrophobic amino acid), including H3K14Ac and H4K20Ac. We determined the crystal structures of Sth1BD at 2.40 Å resolution and Sth1BD-H3K14Ac complex at 1.40 Å resolution. The extensive interfaces between Sth1BD and H36-21 facilitate the specific and robust binding of Sth1BD to H3K14Ac. Our studies provide insights into how the RSC complex recognizes H3K14Ac to orchestrate the crosstalk between histone acetylation and chromatin remodeling.


Assuntos
Proteínas de Ciclo Celular/química , Proteínas de Ciclo Celular/metabolismo , Histonas/química , Histonas/metabolismo , Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Acetilação , Sítios de Ligação , Montagem e Desmontagem da Cromatina , Cristalografia por Raios X , Lisina/metabolismo , Modelos Moleculares , Conformação Proteica , Domínios Proteicos , Saccharomyces cerevisiae/química
14.
Nat Commun ; 11(1): 4206, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32826896

RESUMO

Saccharomyces cerevisiae TBP associated factor 14 (Taf14) is a well-studied transcriptional regulator that controls diverse physiological processes and that physically interacts with at least seven nuclear complexes in yeast. Despite multiple previous Taf14 structural studies, the nature of its disparate transcriptional regulatory functions remains opaque. Here, we demonstrate that the extra-terminal (ET) domain of Taf14 (Taf14ET) recognizes a common motif in multiple transcriptional coactivator proteins from several nuclear complexes, including RSC, SWI/SNF, INO80, NuA3, TFIID, and TFIIF. Moreover, we show that such partner binding promotes liquid-liquid phase separation (LLPS) of Taf14ET, in a mechanism common to YEATS-associated ET domains (e.g., AF9ET) but not Bromo-associated ET domains from BET-family proteins. Thus, beyond identifying the molecular mechanism by which Taf14ET associates with many transcriptional regulators, our study suggests that Taf14 may function as a versatile nuclear hub that orchestrates transcriptional machineries to spatiotemporally regulate diverse cellular pathways.


Assuntos
Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Fator de Transcrição TFIID/metabolismo , Proteínas de Transporte , Proteínas de Ciclo Celular/metabolismo , Análise por Conglomerados , Proteínas de Ligação a DNA , Epigenômica , Regulação Fúngica da Expressão Gênica , Modelos Moleculares , Proteínas Nucleares/metabolismo , Ligação Proteica , Conformação Proteica , Domínios Proteicos , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genética , Fator de Transcrição TFIID/química , Fator de Transcrição TFIID/genética , Fatores de Transcrição/metabolismo
15.
Front Neurosci ; 14: 614012, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33390894

RESUMO

PURPOSE: Previous studies have revealed increased frontal brain activation during speech comprehension in background noise. Few, however, used tonal languages. The normal pattern of brain activation during a challenging speech-in-nose task using a tonal language remains unclear. The Mandarin Hearing-in-Noise Test (HINT) is a well-established test for assessing the ability to interpret speech in background noise. The current study used Mandarin HINT (MHINT) sentences and functional magnetic resonance imaging (fMRI) to assess brain activation with MHINT sentences. METHODS: Thirty native Mandarin-speaking subjects with normal peripheral hearing were recruited. Functional MRI was performed while subjects were presented with either HINT "clear" sentences with low-level background noise [signal-to-noise ratio (SNR) = +3 dB] or "noisy" sentences with high-level background noise (SNR = -5 dB). Subjects were instructed to answer with a button press whether a visually presented target word was included in the sentence. Brain activation between noisy and clear sentences was compared. Activation in each condition was also compared to a resting, no sentence presentation, condition. RESULTS: Noisy sentence comprehension showed increased activity in areas associated with tone processing and working memory, including the right superior and middle frontal gyri [Brodmann Areas (BAs) 46, 10]. Reduced activity with noisy sentences was seen in auditory, language, memory and somatosensory areas, including the bilateral superior and middle temporal gyri, left Heschl's gyrus (BAs 21, 22), right temporal pole (BA 38), bilateral amygdala-hippocampus junction, and parahippocampal gyrus (BAs 28, 35), left inferior parietal lobule extending to left postcentral gyrus (BAs 2, 40), and left putamen. CONCLUSION: Increased frontal activation in the right hemisphere occurred when comprehending noisy spoken sentences in Mandarin. Compared to studies using non-tonal languages, this activation was strongly right-sided and involved subregions not previously reported. These findings may reflect additional effort in lexical tone perception in this tonal language. Additionally, this continuous fMRI protocol may offer a time-efficient way to assess group differences in brain activation with a challenging speech-in-noise task.

16.
Front Pharmacol ; 9: 743, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30087610

RESUMO

Background: Xuebijing injection (XBJ), transforming from Xuefuzhuyu decoction, is the only Chinese medicine injection approved for sepsis. XBJ and ulinastatin (UTI) combination therapy is supposed to be beneficial for sepsis patients. To fill the gap between the lack of evidence for the efficacy of combination therapy and its increasing application among patients, an extensive meta-analysis was performed. Methods: Eight databases were searched to identify randomized controlled trials (RCTs) comparing XBJ plus UTI with UTI alone in treating sepsis from inception to February 5, 2018. Data extraction and methodological quality assessment of the included RCTs were implemented by two investigators independently. All data were synthesized and analyzed utilizing Review Manager 5.3. Results: Seventeen RCTs with a total of 1,247 participants corresponded with the inclusion criteria of our study. The findings reflected that in comparison to single UTI, XBJ and UTI combination therapy could significantly lower 28-day mortality (RR = 0.54, 95% CI [0.39, 0.73], P < 0.0001), shorten duration of mechanical ventilation (SMD = -1.13, 95% CI [-1.30, -0.95], P < 0.00001), reduce length of ICU stay (SMD = -0.84, 95% CI [-1.00, -0.67], P < 0.00001), and decrease APACHE II score (SMD = -1.09, 95% CI [-1.49, -0.69], P < 0.00001). Additionally, XBJ plus UTI had superiority over single UTI in lowering PCT levels (SMD = -1.61, 95% CI [-2.23, -0.98], P < 0.00001), and improving inflammatory cytokines-IL-6 and TNF-α levels (SMD = -1.45, 95% CI [-1.71, -1.19], P < 0.00001; SMD = -1.11, 95% CI [-1.42, -0.80], P < 0.00001). Moreover, CRP, hs-CRP, and LPS levels were remarkably reduced by XBJ plus UTI compared with UTI alone (SMD = -1.50, 95% CI [-2.00, -1.00], P < 0.00001; SMD = -1.31, 95% CI [-1.70, -0.93], P < 0.00001; SMD = -1.17, 95% CI [-1.42, -0.92], P < 0.00001). Three studies involving 14 patients reported the occurrences of adverse events. Conclusions: Comparing with UTI alone, XBJ and UTI combination therapy appeared to be more effective for sepsis. However, owing to the limitations of this meta-analysis, additional RCTs with higher-quality and more rigorous design are needed to confirm our findings.

17.
J Zhejiang Univ Sci ; 4(4): 480-4, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12861627

RESUMO

Eleven red soils varying in land use and fertility status were used to examine the effect of land use on microbial biomass -C, -N and -P. Microbial biomass-C in the red soils ranged from about 68 mg C/kg to 225 mg C/kg, which is generally lower than that reported from other types of soil, probably because of low organic matter and high acidity in the red soils. Land use had considerable effects on the amounts of soil C(mic). The C(mic) was the lowest in eroded fallow land, followed by woodland, tea garden, citrus grove and fallow grassland, and the highest in vegetable and paddy fields. There was significant correlation between C(mic) and organic matter content, suggesting that the influence of land use on C(mic) is mainly related to the input and accumulation of organic matter. Microbial biomass-N in the soils ranged from 12.1 Nmg/kg to 31.7 Nmg/kg and was also affected by land use. The change of N(mic) with land use was similar to that of C(mic). The microbial C/N ratio ranged from 5.2 to 9.9 and averaged 7.6. The N(mic) was significantly correlated with soil total N and available N. Microbial biomass-P in the soils ranged from 4.5 mg P/kg to 52.3 mg P/kg. The microbial C/P ratio was in the range of 4 - 23. The P(mic) was relatively less affected by land use due to differences in fertilization practices for various land use systems.


Assuntos
Agricultura/métodos , Biomassa , Carbono/análise , Ecossistema , Nitrogênio/análise , Fósforo/análise , Microbiologia do Solo , Solo/análise , Conservação dos Recursos Naturais
18.
J Environ Monit ; 10(4): 508-16, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18385872

RESUMO

Water quality throughout south Florida has been a major concern for many years. Nutrient enrichment in the Indian River Lagoon (IRL) is a major surface water issue and is suggested as a possible cause of symptoms of ecological degradation. In 2005-06, water samples were collected weekly from seven sites along Ten Mile Creek (TMC), which drains into the Indian River Lagoon, to investigate and analyze spatial and temporal fluctuations of nutrients nitrogen (N) and phosphorus (P). The objective of this study was to understand the relationships among chlorophyll a concentration, nutrient enrichment and hydrological parameters in the surface water body. High median concentrations of total P (TP, 0.272 mg L(-1)), PO4-P (0.122 mg L(-1)), and dissolved total P (DTP, 0.179 mg L(-1)); and total N (TN, 0.988 mg L(-1)), NO3(-)-N (0.104 mg L(-1)), NH4+-N (0.103 mg L(-1)), and total Kjeldahl N (TKN, 0.829 mg L(-1)), were measured in TMC. The concentrations of TP, PO4-P, DTP, TN, NO3(-)-N, NH4+-N, and TKN were higher in summer and fall than in winter and spring. However, chlorophyll a and pheophytin concentrations during this period in TMC varied in the range of 0.000-60.7 and 0.000-17.4 microg L(-1), with their median values of 3.54 and 3.02 microg L(-1), respectively. The greatest mean chlorophyll a (10.3 microg L(-1)) and pheophytin (5.71 microg L(-1)) concentrations occurred in spring, while the lowest chlorophyll a (1.49 microg L(-1)) and pheophytin (1.97 mug L(-1)) in fall. High concentrations of PO4-P (>0.16 mg L(-1)), DTP (>0.24 mg L(-1)), NO3(-)-N (>0.15 mg L(-1)), NH4+-N (>0.12 mg L(-1)), and TKN (>0.96 mg L(-1)), occurred in the upstream of TMC, while high concentrations of chlorophyll a (>6.8 mug L(-l)) and pheophytin (>3.9 microg L(-l)) were detected in the downstream of TMC. The highest chlorophyll a (11.8 mug L(-l)) and pheophytin (6.06 microg L(-l)) concentrations, however, were associated with static and open water conditions. Hydrological parameters (total dissolved solid, electrical conductivity, salinity, pH, and water temperature) were positively correlated with chlorophyll a and pheophytin concentrations (P < 0.01) and these factors overshadowed the relationships between N and P concentrations and chlorophyll a under field conditions. Principal component analysis and the ratios of DIN/DP and TN/TP in the water suggest that N is the limiting nutrient factor for phytoplankton growth in the TMC and elevated N relative to P is beneficial to the growth of phytoplankton, which is supported by laboratory culture experiments under controlled conditions.


Assuntos
Nitrogênio/análise , Fósforo/análise , Fitoplâncton/crescimento & desenvolvimento , Rios/química , Agricultura , Biomassa , Clorofila/análise , Eutrofização , Florida , Sistemas de Informação Geográfica , Feofitinas/análise , Estações do Ano
19.
Artigo em Inglês | MEDLINE | ID: mdl-15792301

RESUMO

Cadmium (Cd) has received considerable attention because of its association with various human health problems. The behavior of adsorption-desorption of Cd at contaminated levels in two variable charge soils were investigated. The red soil (RAR) developed on the Arenaceous rock (clayey, mixed siliceous thermic typic Dystrochrept) adsorbed more Cd2+ than the red soil (REQ) derived from the Quaternary red earths (clayey, kaolinitic thermic plinthite Aquult). The characteristics of Cd adsorption could be described by the Freundlich equation (r2 = 0.997 and 0.989, respectively, for the RAR and REQ) and the simple Langmuir adsorption equation (r2 = 0.985 and 0.977, respectively, for the RAR and REQ). The maximum adsorption values (Xm) that were obtained from the simple Langmuir model were 36.23 mmol Cd2+ kg(-1) soil and 31.15 mmol Cd2+ kg(-1) soil, respectively for the RAR and REQ. Adsorption of Cd2+ decreased soil pH by 1.28 unit for the RAR soil and 1.23 unit for the REQ soil at the highest loading. The distribution coefficient (kd) of Cd in the soil decreased exponentially with increasing Cd2+ loading. The adsorption of cadmium in the two variable charge soils was characterized by a rapid process that lasted approximately 15 min, followed by a slower but longer period. 85.5% and 79.4% of the added Cd were adsorbed within two hours by the RAR and REQ soil, respectively. More Cd2+ was adsorbed at 10 degrees C than at 25 degrees C or 40 degrees C. After five successive desorptions with 0.01 mol L(-1) NaNO3 solution, 53.3% of the total adsorbed Cd2+ in the RAR soil was desorbed and the corresponding value of the REQ soil was 46.5%, indicating that the RAR soil had a lower affinity for Cd2+ than the REQ soil at the same Cd2+ loading.


Assuntos
Cádmio/análise , Poluentes do Solo/análise , Adsorção , Cádmio/química , China , Concentração de Íons de Hidrogênio , Caulim , Modelos Teóricos , Nitratos/química , Silício , Temperatura , Fatores de Tempo
20.
Ying Yong Sheng Tai Xue Bao ; 14(2): 179-83, 2003 Feb.
Artigo em Zh | MEDLINE | ID: mdl-12827866

RESUMO

Soil basal respiration potential, metabolic quotient (qCO2), and activities of urease, invertase and acid phosphomonoesterase were investigated in the root-layer of 10-, 40-, and 90-yr-old tea bushes grown on the same type of red soil. The soil daily basal respiration potential ranged from 36.23 to 58.52 mg.kg-1.d-1, and the potentials in the root-layer of 40- or 90-yr-old were greater than that of 10-yr old tea bushes. The daily qCO2, ranging from 0.30 to 0.68, was in the reverse trend. The activities of test three enzymes changed differently with tea bushes' age. Urease activity in the root-layer of all age tea bushes ranged from 41.48 to 47.72 mg.kg-1.h-1 and slightly decreased with tea bushes' age. Invertase activity was 189.29-363.40 mg.kg-1.h-1 and decreased with tea bushes' age, but its activity in the root-layer of 10-year old tea bushes was significantly greater than that in the root-layer soil of 40- or 90-year old tea bushes. Acid phosphomonoesterase activity (444.22-828.32 mg.kg-1.h-1) increased significantly with tea bushes' age. Soil basal respiration potential, qCO2 and activities of 3 soil enzymes were closely related to soil pH, soil organic carbon, total nitrogen and C/N ratio, total soluble phenol, and microbial biomass carbon, respectively.


Assuntos
Raízes de Plantas/metabolismo , Solo/análise , Chá/metabolismo , Glicosídeo Hidrolases/metabolismo , Consumo de Oxigênio , Urease/metabolismo , beta-Frutofuranosidase
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