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1.
Artigo em Inglês | MEDLINE | ID: mdl-35499729

RESUMO

The geometric structure of the suspended carrier is an important factor that directly affects the effluent quality of the moving bed biofilm reactor, and it should be a valuable mathematical solution to solve the nonlinear equation through numerical simulation and experimental research. Therefore, this study has designed and prepared a coral-shaped fractal suspension carrier based on nonlinear equations and verified the effectiveness of the new carrier for sewage treatment through FLUENT numerical simulation and domestic sewage treatment experiments. The experimental results show that the coral-shaped fractal suspension carrier has a significant effect on the velocity, vortex distribution, and gas-phase distribution of the flow field in the reactor. The mass transfer dead area in the reactor is reduced, the number of vortices is significantly increased, and the fractal dimension of the carrier is negatively correlated with the flow velocity and pressure drop of the fluid. After stabilization, the average removal rates of COD and NH4+-N by the reactor are 89.5% and 93.21%, respectively; the effluent quality reaches the national first-class A standard; and the sewage treatment performance is good. At the same time, this research provides a preliminary research basis for the method of solving nonlinear equations through numerical simulation and experimental research.

2.
Neurobiol Aging ; 112: 212-214, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35240489

RESUMO

Recently, homozygous missense variants in ANXA1 were identified to cause parkinsonism by segregation analysis in a consanguineous family. However, no further replication has been conducted in a wider range of Parkinson's disease (PD) populations. To investigate the involvement of ANXA1 mutations in PD, we analyzed the rare variants in 743 Chinese early-onset PD (EOPD) patients (age at onset <50) using whole exome sequencing. The over-representation of rare variants in patients was examined with Fisher's exact test at allele and gene levels. We did not find the disease-causing variant described in the original study, and no patient carried other homozygous or compound heterozygous variants of ANXA1. Six rare missense mutations in ANXA1 were identified (minor allele frequency <0.01). No significant association was found between ANXA1 variants and PD at allele and gene levels. Genetic screening of ANXA1 mutations suggested rare variants of ANXA1 were rare in EOPD in the Asian ethnic background. Further explorations with larger sample size were warranted to better understand the role of ANXA1 in PD.


Assuntos
Anexina A1 , Doença de Parkinson , Idade de Início , Anexina A1/genética , Homozigoto , Humanos , Mutação/genética , Doença de Parkinson/genética , Sequenciamento Completo do Exoma
3.
Comput Struct Biotechnol J ; 20: 1286-1294, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35356546

RESUMO

Intrinsic disorder prediction is an active area that has developed over 100 predictors. We identify and investigate a recent trend towards the development of deep neural network (DNN)-based methods. The first DNN-based method was released in 2013 and since 2019 deep learners account for majority of the new disorder predictors. We find that the 13 currently available DNN-based predictors are diverse in their topologies, sizes of their networks and the inputs that they utilize. We empirically show that the deep learners are statistically more accurate than other types of disorder predictors using the blind test dataset from the recent community assessment of intrinsic disorder predictions (CAID). We also identify several well-rounded DNN-based predictors that are accurate, fast and/or conveniently available. The popularity, favorable predictive performance and architectural flexibility suggest that deep networks are likely to fuel the development of future disordered predictors. Novel hybrid designs of deep networks could be used to adequately accommodate for diversity of types and flavors of intrinsic disorder. We also discuss scarcity of the DNN-based methods for the prediction of disordered binding regions and the need to develop more accurate methods for this prediction.

4.
Environ Toxicol Pharmacol ; 92: 103847, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35283284

RESUMO

The purpose of this study was to assess the risk of aflatoxins due to multiple food consumption among the Zhejiang population. Ultra-high-performance liquid chromatography coupled with tandem mass spectrometry method was used to determine aflatoxins in 792 samples. Aflatoxins were detected in 27.1% of the samples at levels between 0.07 and 262.63 µg kg-1, and aflatoxins B1 was the most frequently detected among different types of samples. 0.8% of peanut oil, 3.39% of nut products as well as 1.1% of condiments contaminated with aflatoxins B1 exceeded China national tolerance limits. Peanut oil had the highest incidence of aflatoxin, with a range from 0.17 to 22.50 µg kg-1. Using bags conferred limited advantages in reducing aflatoxin contents. Moreover, peanut and rice were the main contributors to dietary exposure to aflatoxins among Zhejiang residents. Finally, the margin of exposure values obtained by rice consumption were far from the safe margin of 10,000, indicating a potential risk to public health. The results pointed out the need for further prioritization of aflatoxins B1 risk-management actions in Zhejiang.

5.
Clin Epigenetics ; 14(1): 15, 2022 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-35073982

RESUMO

BACKGROUND: Lung cancer is one of most common cancers worldwide, with a 5-year survival rate of less than 20%, which is mainly due to late-stage diagnosis. Noninvasive methods using 5-hydroxymethylation of cytosine (5hmC) modifications and fragmentation profiles from 5hmC cell-free DNA (cfDNA) sequencing provide an opportunity for lung cancer detection and management. RESULTS: A total of 157 lung cancer patients were recruited to generate the largest lung cancer cfDNA 5hmC dataset, which mainly consisted of 62 lung adenocarcinoma (LUAD), 48 lung squamous cell carcinoma (LUSC) and 25 small cell lung cancer (SCLC) patients, with most patients (131, 83.44%) at advanced tumor stages. A 37-feature 5hmC model was constructed and validated to distinguish lung cancer patients from healthy controls, with areas under the curve (AUCs) of 0.8938 and 0.8476 (sensitivity = 87.50% and 72.73%, specificity = 83.87% and 80.60%) in two distinct validation sets. Furthermore, fragment profiles of cfDNA 5hmC datasets were first explored to develop a 48-feature fragmentation model with good performance (AUC = 0.9257 and 0.822, sensitivity = 87.50% and 78.79%, specificity = 80.65% and 76.12%) in the two validation sets. Another diagnostic model integrating 5hmC signals and fragment profiles improved AUC to 0.9432 and 0.8639 (sensitivity = 87.50% and 83.33%, specificity = 90.30% and 77.61%) in the two validation sets, better than models based on either of them alone and performing well in different stages and lung cancer subtypes. Several 5hmC markers were found to be associated with overall survival (OS) and disease-free survival (DFS) based on gene expression data from The Cancer Genome Atlas (TCGA). CONCLUSIONS: Both the 5hmC signal and fragmentation profiles in 5hmC cfDNA data are sensitive and effective in lung cancer detection and could be incorporated into the diagnostic model to achieve good performance, promoting research focused on clinical diagnostic models based on cfDNA 5hmC data.


Assuntos
5-Metilcitosina/análogos & derivados , Fragmentação do DNA/efeitos dos fármacos , Neoplasias Pulmonares/genética , 5-Metilcitosina/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , China/epidemiologia , Metilação de DNA/efeitos dos fármacos , Metilação de DNA/genética , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade
6.
Neurol Sci ; 43(2): 1435-1439, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34993657

RESUMO

CASE REPORTS: An elderly Chinese male patient was diagnosed with compound heterozygous spinocerebellar ataxia type 8; molecular diagnosis found that the (CTA)n(CTG)n repeat unit of his ATXN8/ATXN8OS gene was 134/93. The patient has a 6-year medical history, mainly manifested by ataxia, dysarthria, abnormal eye movements, and pyramidal signs. Magnetic resonance imaging (MRI) showed no obvious abnormalities in the medulla oblongata and cervical spinal cord except for cerebellar atrophy and sulci enlargement. There are heterozygous SCA8 individuals among his family members, but there are significant differences in their onset age and clinical manifestations. DISCUSSION AND CONCLUSION: This case reminds us that (CTA)n(CTG)n repeats are very prone to dynamic mutations in intergenerational inheritance, and the ATXN8/ATXN8OS gene penetrance is different in different SCA8 individuals, which suggests that genetic detection is of great importance.


Assuntos
Ataxias Espinocerebelares , Degenerações Espinocerebelares , Idoso , China , Heterozigoto , Humanos , Masculino , Ataxias Espinocerebelares/diagnóstico por imagem , Ataxias Espinocerebelares/genética , Degenerações Espinocerebelares/diagnóstico por imagem , Degenerações Espinocerebelares/genética , Expansão das Repetições de Trinucleotídeos/genética
7.
NPJ Parkinsons Dis ; 8(1): 11, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-35058467

RESUMO

The neutrophil-to-lymphocyte ratio (NLR), an inflammatory marker, can predict the prognosis of neurodegenerative diseases. However, the significance of NLR for the prognosis of multiple system atrophy (MSA) has not been reported. We aimed to examine the prognostic significance of NLR in MSA. A total of 169 MSA patients and 163 matched healthy controls (HCs) were enrolled. MSA patients were divided into three groups according to the tertiles of their NLR. Kaplan-Meier survival analysis and Cox regression model were used to assessing the effect of NLR on survival. An independent validation cohort of 56 consecutive patients with probable MSA who met the inclusion criteria was included. The NLR was significantly higher in patients with MSA than that in HCs. The survival duration in patients with MSA in group 3 was shorter than that in patients in the other two groups (P = 0.013). In the multivariable Cox regression model, a higher NLR increased the risk of mortality in patients with MSA after adjusting for confounding factors (HR = 1.922, P = 0.035). Additionally, a higher NLR increased the risk of mortality in MSA with predominant cerebellar ataxia (MSA-C) (HR = 2.398, P = 0.033) and in men (HR = 3.483, P = 0.027). The concordance index for the multivariate Cox regression model was more than 0.7 both in the primary cohort and external validation cohort. Patients with MSA had a higher NLR than did HCs. A high NLR increased the risk of mortality with MSA, especially in MSA-C and in men.

9.
Mov Disord ; 37(2): 421-426, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34719813

RESUMO

BACKGROUND: Neurofilament light chain (NFL), a potential biomarker of multiple system atrophy (MSA), has been reported in several studies. OBJECTIVES: The objective of this study was to investigate whether plasma NFL levels are correlated with the progression of motor and cognition function in MSA. METHODS: Patients with MSA were part of a prospective cohort study with assessments at baseline and after 1 year. Plasma NFL was quantified using ultrasensitive Simoa technology. RESULTS: A total of 91 patients with MSA and 60 healthy controls (HCs) were enrolled. NFL levels increased from baseline to 1-year follow-up (P = 0.010). Baseline plasma NFL levels were significantly associated with motor severity and progression in patients with MSA (P < 0.05) but not with cognitive progression (P > 0.05). CONCLUSIONS: Plasma NFL is a reliable biomarker for the disease severity of MSA and monitoring the progression of MSA, but not the progression of cognition. © 2021 International Parkinson and Movement Disorder Society.


Assuntos
Atrofia de Múltiplos Sistemas , Biomarcadores , Progressão da Doença , Humanos , Filamentos Intermediários , Atrofia de Múltiplos Sistemas/diagnóstico , Estudos Prospectivos , Índice de Gravidade de Doença
10.
Neurology ; 98(1): e73-e82, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34663646

RESUMO

BACKGROUND AND OBJECTIVES: Nonmotor symptoms are common in patients with multiple system atrophy (MSA), but there is limited knowledge regarding fatigue in MSA. This study aimed to investigate the frequency and evolution of fatigue and the factors related to fatigue and its progression in patients with MSA at an early stage. METHODS: Patients with probable MSA were comprehensively evaluated at both baseline and the 1-year follow-up, including their motor and nonmotor symptoms. Fatigue and anxiety were assessed using the Fatigue Severity Scale (FSS) and Hamilton Anxiety Rating Scale (HARS), respectively. Orthostatic hypotension (OH) was defined as a decrease in the systolic or diastolic blood pressure by at least 30 and 15 mm Hg, respectively. The binary logistic regression model and linear regression model were used to analyze the factors related to fatigue and its progression, respectively. RESULTS: This study enrolled 146 patients with MSA. The frequency of fatigue was 60.3%, 55.1%, and 64.9% in MSA, MSA with predominant parkinsonism (MSA-P), and MSA with predominant cerebellar ataxia (MSA-C), respectively. The frequency of fatigue and the FSS score in patients with MSA increased from baseline to the 1-year follow-up (p < 0.05). Young age (odds ratio [OR] 0.939, 95% confidence interval [CI] 0.894-0.987), OH (OR 2.806, 95% CI 1.253-6.286), and high HARS score (OR 1.014, 95% CI 1.035-1.177) were associated with fatigue in MSA. OH was associated with fatigue in MSA-P (OR 3.391, 95% CI 1.066-10.788), while high HARS score was associated with fatigue in MSA-C (OR 1.159, 95% CI 1.043-1.287). In addition, only low FSS scores at baseline were associated with the annual progression rate of FSS scores in MSA, MSA-P, and MSA-C (p < 0.05). Neurofilament light chain, α-synuclein, glial fibrillary acidic protein, brain-derived neurotrophic factor, and triggering receptor expressed on myeloid cell-2 were not significantly associated with fatigue and its progression in MSA. DISCUSSION: Fatigue was prevalent in early-stage MSA, and it increased and remained persistent over time. This study demonstrated that OH and anxiety were associated with fatigue in patients with MSA.


Assuntos
Hipotensão Ortostática , Atrofia de Múltiplos Sistemas , Transtornos de Ansiedade , Fadiga/complicações , Fadiga/etiologia , Humanos , Hipotensão Ortostática/complicações , Atrofia de Múltiplos Sistemas/complicações , Atrofia de Múltiplos Sistemas/diagnóstico , Atrofia de Múltiplos Sistemas/epidemiologia , Estudos Prospectivos
11.
Neurobiol Aging ; 109: 273-278, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34544586

RESUMO

Altered ubiquitin signaling and disrupted protein quality control have been implicated in the pathogenesis of PD. The aim of the study was to systematically examine the overlaps between E3 ubiquitin ligase genes and early onset PD (EOPD). A total of 695 EOPD patients were analyzed aggregate burden for rare variants (MAF <0.001 and MAF <0.0001) in a total of 44 E3 ubiquitin ligase genes causing disorders involved in the nervous system. There was significant enrichment of the rare and rare damaging variants in the E3 ubiquitin ligase genes in EOPD patients. Detailly, in the gene-based level, the strongest associations were found in HERC1, IRF2BPL, KMT2D, RAPSN, RLIM, RNF168 and RNF216. Our findings highlighted the importance of UPS mechanism in the pathogenesis of PD from the genetic perspective. Moreover, our study also expanded the susceptible gene spectrum for PD.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença/genética , Variação Genética/genética , Doença de Parkinson/genética , Ubiquitina-Proteína Ligases/genética , Idade de Início , Proteínas de Transporte , Proteínas de Ligação a DNA , Feminino , Humanos , Masculino , Proteínas de Neoplasias , Proteínas Nucleares
12.
Gene ; 813: 146117, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34902511

RESUMO

OBJECTIVES: The purpose of this research was to confirm the prognostic value of bestrophin-2 (BEST2), one of the hub genes in colon cancer, via bioinformatics analysis and validation in public databases and immunohistochemistry detection. METHODS: The GEO2R online tool and Venn diagram software were utilized to identify differentially expressed genes (DEGs) from expression profiles, including GSE20916, GSE44861 and GSE74602, from the Gene Expression Omnibus (GEO). The overall survival (OS) and disease-free survival (DFS) of colon cancer patients from The Cancer Genome Atlas (TCGA) were analyzed through Kaplan-Meier survival curves. Verification of the significance of BEST2 in colon cancer was based on TCGA, Genotype Tissue Expression (GTEx) and 10 datasets from GEO. BEST2 expression was detected with immunohistochemistry (IHC) in 330 colon tissue samples on microarrays including 165 colon cancerand 165 adjacent normal tissues. For further validation, comprehensive analysis from tissue microarrays and multiple datasets was performed by the summarizing of receiver operating characteristic (SROC) curves and the standard mean differences (SMDs). BEST2 expression in various kinds of colon cancer tissues and cell lines in the context of pancancer was obtained from the Expression Atlas database. The CBioPortal database was queried to identify BEST2 gene alterations and mutation status in colon cancer. Correlated genes (CEGs) with BEST2 and DEGs from public database data were assembled for functional and pathway enrichment analysis. RESULTS: We identified 85 DEGs from the three datasets and screened out BEST2 as a prognostic predictor via the TCGA database. Colon cancer patients with high expression of BEST2 had better survival than patients with low BEST2 (HR = 0.5, P = 0.006) as shown in Kaplan-Meier survival curves in GEPIA. In all, 1463 colon cancer tissues and 1023 colon normal tissues were gathered via public databases as well as in-house tissue microarrays. The comprehensiveexpression analysis suggested low-expression of BEST2 in colon cancer (SMD = -2.48, 95% CI [-3.15- -1.80]) and the notable efficacy of BEST2 expression in differentiating colon cancer from noncancer samples (AUC = 0.97). Gene alteration status of BEST2 occurred in 5% of colon cancer cases, mostly missense mutations and deep deletions. Genes positively correlated with BEST2 and DEGs primarily aggregated in pathways such as anion absorption, digestive juice secretion, cAMP signaling and so on (P < 0.05). CONCLUSION: Ampleevidencesupportsthe role of BEST2 in distinguishing colon cancer from normal tissues in this research. Low expression of BEST2 is correlated with a shorter OS, which implies that BEST2 can be employed as a potential biomarker and therapeutictarget in colon cancer.


Assuntos
Bestrofinas/genética , Neoplasias do Colo/genética , Bestrofinas/biossíntese , Bestrofinas/metabolismo , Biomarcadores Tumorais/genética , Neoplasias do Colo/metabolismo , Biologia Computacional , Bases de Dados Genéticas , Expressão Gênica , Redes Reguladoras de Genes , Humanos , Estimativa de Kaplan-Meier , Prognóstico , Mapas de Interação de Proteínas , Software , Transcriptoma
13.
Brief Bioinform ; 23(1)2022 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-34905768

RESUMO

Proteins with intrinsically disordered regions (IDRs) are common among eukaryotes. Many IDRs interact with nucleic acids and proteins. Annotation of these interactions is supported by computational predictors, but to date, only one tool that predicts interactions with nucleic acids was released, and recent assessments demonstrate that current predictors offer modest levels of accuracy. We have developed DeepDISOBind, an innovative deep multi-task architecture that accurately predicts deoxyribonucleic acid (DNA)-, ribonucleic acid (RNA)- and protein-binding IDRs from protein sequences. DeepDISOBind relies on an information-rich sequence profile that is processed by an innovative multi-task deep neural network, where subsequent layers are gradually specialized to predict interactions with specific partner types. The common input layer links to a layer that differentiates protein- and nucleic acid-binding, which further links to layers that discriminate between DNA and RNA interactions. Empirical tests show that this multi-task design provides statistically significant gains in predictive quality across the three partner types when compared to a single-task design and a representative selection of the existing methods that cover both disorder- and structure-trained tools. Analysis of the predictions on the human proteome reveals that DeepDISOBind predictions can be encoded into protein-level propensities that accurately predict DNA- and RNA-binding proteins and protein hubs. DeepDISOBind is available at https://www.csuligroup.com/DeepDISOBind/.


Assuntos
Proteínas de Ligação a DNA/química , DNA/química , Aprendizado Profundo , Proteínas Intrinsicamente Desordenadas/química , Proteínas de Ligação a RNA/química , RNA/química , Biologia Computacional/métodos , DNA/metabolismo , Proteínas de Ligação a DNA/metabolismo , Humanos , Redes Neurais de Computação , Ácidos Nucleicos/metabolismo , Ligação Proteica , Proteoma/metabolismo , RNA/metabolismo , Proteínas de Ligação a RNA/metabolismo
14.
Front Genet ; 12: 740052, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868212

RESUMO

Background: CYLD Lysine 63 Deubiquitinase gene (CYLD) was recently identified to be a novel causative gene for frontal temporal dementia (FTD)-amyotrophic lateral sclerosis (ALS). In the current study, we aimed to (1) systematically screen the mutations of CYLD in a large cohort of Chinese ALS patients, (2) study the genotype-phenotype correlation, and (3) explore the role of CYLD in ALS via rare variants burden analysis. Methods: A total of 978 Chinese sporadic ALS (sALS) patients and 46 familial ALS (fALS) patients were sequenced with whole-exome sequencing and analyzed rare variants in CYLD with minor allele frequency <0.1%. Results: In total, seven rare missense variants in CYLD have been identified in 7 (0.72%) patients among 978 sALS patients. Two (4.3%) rare missense variants were identified among the 46 fALS cases, in which one patient was diagnosed as having comorbidity of ALS and progressive supranuclear palsy (PSP). Moreover, the burden analysis indicated no enrichment of rare variants in CYLD among patients with ALS. Conclusion: In conclusion, our study extended the genotype and phenotype of CYLD in ALS, but the pathogenicity of these variants needs to be further verified. Moreover, burden analysis argued against the role of CYLD in the pathogenesis of ALS. More studies from different ethnicities would be needed.

15.
Front Genet ; 12: 765833, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868249

RESUMO

Background: The association between inflammation and neurodegeneration has long been observed in parkinson's disease (PD) and multiple system atrophy (MSA). Previous genome-wide association studies (GWAS) and meta-analyses have identified several risk loci in inflammation-associated genes associated with PD. Objective: To investigate whether polymorphisms in some inflammation-associated genes could modulate the risk of developing PD and MSA in a Southwest Chinese population. Methods: A total of 2,706 Chinese subjects comprising 1340 PD, 483 MSA and 883 healthy controls were recruited in the study. Three polymorphisms (rs2074404 GG/GT/TT, rs17425622 CC/CT/TT, rs34043159 CC/CT/TT) in genes linked to inflammation in all the subjects were genotyped by using the Sequenom iPLEX Assay. Results: The allele G of WNT3 rs2074404 can increase risk on PD (OR: 1.048, 95% CI: 1.182-1.333, p = 0.006), exclusively in the LOPD subgroup (OR: 1.166, 95% CI:1.025-1.327, p = 0.019), but not in EOPD or MSA. And the recessive model analysis also demonstrated an increased PD risk in GG genotype of this locus (OR = 1.331, p = 0.007). However, no significant differences were observed in the genotype distributions and alleles of HLA-DRB5 rs17425622 and IL1R2 rs34043159 between the PD patients and controls, between the MSA patients and controls, or between subgroups of PD or MSA and controls. Conclusion: Our results suggested the allele G of WNT3 rs2074404 have an adverse effect on PD and particularly, on the LOPD subgroup among a Chinese population.

16.
Expert Rev Proteomics ; 18(12): 1019-1029, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34894985

RESUMO

INTRODUCTION: Intrinsic disorder prediction field develops, assesses, and deploys computational predictors of disorder in protein sequences and constructs and disseminates databases of these predictions. Over 40 years of research resulted in the release of numerous resources. AREAS COVERED: We identify and briefly summarize the most comprehensive to date collection of over 100 disorder predictors. We focus on their predictive models, availability and predictive performance. We categorize and study them from a historical point of view to highlight informative trends. EXPERT OPINION: We find a consistent trend of improvements in predictive quality as newer and more advanced predictors are developed. The original focus on machine learning methods has shifted to meta-predictors in early 2010s, followed by a recent transition to deep learning. The use of deep learners will continue in foreseeable future given recent and convincing success of these methods. Moreover, a broad range of resources that facilitate convenient collection of accurate disorder predictions is available to users. They include web servers and standalone programs for disorder prediction, servers that combine prediction of disorder and disorder functions, and large databases of pre-computed predictions. We also point to the need to address the shortage of accurate methods that predict disordered binding regions.


Assuntos
Biologia Computacional , Proteínas Intrinsicamente Desordenadas , Sequência de Aminoácidos , Bases de Dados de Proteínas , Humanos , Aprendizado de Máquina
17.
Front Aging Neurosci ; 13: 701906, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34744684

RESUMO

Objective: To explore the frequency, evolution, associated factors, and risk factors of fatigue over 3-year of prospective follow-up in a cohort of patients with early Parkinson's disease (PD). Methods: A total of 174 PD patients in the early stage were enrolled and quantitively assessed motor and non-motor symptoms using comprehensive scales including the Fatigue Severity Scale (FSS) annually. Each subject was categorized as PD with and without fatigue based on a cut-off mean value of 4 using FSS. The generalized estimating equation (GEE) was utilized to investigate the associated factors, and the stepwise binary logistic regression model was performed to explore the predictors. Results: The frequency of fatigue was slightly changed (ranging from 35.1 to 40.4%) during the 3-year follow-up. The changed pattern of the frequency of fatigue was similar to that of anxiety. Fatigue was significantly associated with nocturnal sleep disorders (B 2.446, P < 0.001), high Hamilton Anxiety Rating Scale (HAMA) score (B 1.072, P = 0.011), and high Unified PD Rating Scale (UPDRS) III score (B 1.029, P = 0.003) over time. High UPDRS III score [odds ratio (OR) 1.051, P = 0.015] at baseline increased the risk of developing fatigue after 1-year; high LEDD (OR 1.002, P = 0.037) increased the risk of developing fatigue after 2-year; and high LEDD (OR 1.003, P = 0.049) and high HAMA score (OR 1.077, P = 0.042) increased the risk of developing fatigue after 3-year. Conclusion: Our present study provided evidence of the longitudinal evolution of fatigue in patients with early PD and help clinical management of fatigue.

18.
Front Neurosci ; 15: 749949, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34764851

RESUMO

Objective: Vascular risk factors have been reported to be associated with cognitive impairment (CI) in the general population, but their role on CI in multiple system atrophy (MSA) is unclear. This study aimed to explore the relationship between vascular risk factors and CI in patients with MSA. Methods: The clinical data and vascular risk factors were collected. The Montreal Cognitive Assessment tool was used to test the cognitive function of patients with MSA. Binary logistic regression was used to analyze the correlation between vascular risk factors and CI. Results: A total of 658 patients with MSA with a mean disease duration of 2.55 ± 1.47 years were enrolled. In MSA patients, hypertension was recorded in 20.2%, diabetes mellitus in 10.3%, hyperlipidemia in 10.2%, smoking in 41.2%, drinking in 34.8%, and obesity in 9.6%. The prevalence of CI in patients with MSA, MSA with predominant parkinsonism (MSA-P), and MSA with predominant cerebellar ataxia (MSA-C) was 45.0, 45.1, and 44.9%, respectively. In the binary logistic regression model, patients with more than one vascular risk factors were significantly more likely to have CI in MSA (OR = 4.298, 95% CI 1.456-12.691, P = 0.008) and MSA-P (OR = 6.952, 95% CI 1.390-34.774, P = 0.018), after adjusting for age, sex, educational years, disease duration, and total Unified multiple system atrophy rating scale scores. Conclusion: Multiple vascular risk factors had a cumulative impact on CI in MSA. Therefore, the comprehensive management of vascular risk factors in MSA should not be neglected.

19.
Sci Rep ; 11(1): 22800, 2021 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-34815485

RESUMO

This study employed traditional and advanced echocardiographic techniques to assess comprehensively age- and sex-related changes in cardiovascular structure and function in wildtype (WT) mice. Forty-five normal adult wildtype mice were apportioned to groups based on age and sex: 2-month (young) male or female, and 24-month (old) male or female (n = 13, 13, 13, and 6, respectively). Each underwent 2-dimensional (2D) imaging echocardiography, Doppler, tissue Doppler imaging echocardiography, and speckle-tracking echocardiography (STE) for comparison of cardiovascular structure and function parameters. Compared to the young mice, the old had significantly higher body weight (BW), and lower diastolic and mean arterial pressure. The left ventricular (LV) end-diastolic and end-systolic volumes, and left ventricular mass, were significantly higher in the old mice. Within each sex, the cardiac diastolic and systolic function parameters were comparable between the young and old. Isovolumetric relaxation time (IVRT)/diastolic time interval (DT) and the maximum drop rate of pressure in LV (- dP/dtmax) were significantly lower in the old mice, while the LV relaxation time constant (Tau) was significantly higher. Spearman's rank correlation showed a positive association between IVRT/DT and - dp/dtmax (male r = 0.663; female r = 0.639). Among the males, the maximum rise rate of pressure in LV (+ dp/dtmax), and systolic global longitudinal strains and rates (S-GLS, S-GLSR) were significantly different between the young and old. Spearman's rank correlation showed positive association between S-GLS, S-GLSR and + dp/dtmax (r = 0.709 and r = 0.499). Regarding vascular structure, the ascending aorta systolic and diastolic diameters were significantly higher in the old mice compared with the young. The male mice had progressive, age-related aortic stiffness. Ageing in mice leads to changes in cardiovascular structure and cardiac diastolic function, but systolic function is relatively well preserved in females. Changes in cardiac function and arterial stiffness were more significant in males than females. Traditional ECG is better than STE for evaluating LV diastolic function; STE is better for LV systolic function.


Assuntos
Diástole , Ecocardiografia Doppler/métodos , Ventrículos do Coração/fisiopatologia , Sístole , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda , Fatores Etários , Animais , Feminino , Ventrículos do Coração/diagnóstico por imagem , Masculino , Camundongos , Fatores Sexuais , Disfunção Ventricular Esquerda/diagnóstico por imagem
20.
Front Genet ; 12: 740096, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733315

RESUMO

A loss-of-function variant in Lin-28 Homolog A gene (LIN28A p. R192G, rs558060339) has been identified in two East Asian ancestry patients with early-onset PD (EOPD). Functional studies revealed that such a variant could lead to developmental defects and PD-related phenotype, and the phenotypes could be rescued after correction of the variant. The aim of the study was to screen the variants of LIN28A in Chinese patients with EOPD. A total of 682 EOPD patients were sequenced with whole exome sequencing and the coding and flanking region of LIN28A were analyzed. We identified a rare coding variant, p. P182L, of LIN28A in a Chinese patient with EOPD. Moreover, we also found a 3'-UTR polymorphism (rs4659441) to be associated with an increased risk for PD. However, our rare variant burden analysis did not support a role for LIN28A as a major causal gene for PD.

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