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1.
Viruses ; 16(4)2024 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-38675901

RESUMO

As SARS-CoV-2 continues to evolve and COVID-19 cases rapidly increase among children and adults, there is an urgent need for a safe and effective vaccine that can elicit systemic and mucosal humoral immunity to limit the emergence of new variants. Using the Chinese Hu191 measles virus (MeV-hu191) vaccine strain as a backbone, we developed MeV chimeras stably expressing the prefusion forms of either membrane-anchored, full-length spike (rMeV-preFS), or its soluble secreted spike trimers with the help of the SP-D trimerization tag (rMeV-S+SPD) of SARS-CoV-2 Omicron BA.2. The two vaccine candidates were administrated in golden Syrian hamsters through the intranasal or subcutaneous routes to determine the optimal immunization route for challenge. The intranasal delivery of rMeV-S+SPD induced a more robust mucosal IgA antibody response than the subcutaneous route. The mucosal IgA antibody induced by rMeV-preFS through the intranasal routine was slightly higher than the subcutaneous route, but there was no significant difference. The rMeV-preFS vaccine stimulated higher mucosal IgA than the rMeV-S+SPD vaccine through intranasal or subcutaneous administration. In hamsters, intranasal administration of the rMeV-preFS vaccine elicited high levels of NAbs, protecting against the SARS-CoV-2 Omicron BA.2 variant challenge by reducing virus loads and diminishing pathological changes in vaccinated animals. Encouragingly, sera collected from the rMeV-preFS group consistently showed robust and significantly high neutralizing titers against the latest variant XBB.1.16. These data suggest that rMeV-preFS is a highly promising COVID-19 candidate vaccine that has great potential to be developed into bivalent vaccines (MeV/SARS-CoV-2).


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Imunidade Humoral , Imunidade nas Mucosas , Imunoglobulina A , Vírus do Sarampo , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Animais , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/genética , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , COVID-19/prevenção & controle , COVID-19/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Vírus do Sarampo/imunologia , Vírus do Sarampo/genética , Cricetinae , Imunoglobulina A/sangue , Humanos , Administração Intranasal , Mesocricetus , Feminino
2.
Sci Rep ; 13(1): 4102, 2023 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-36914715

RESUMO

T2 lesion quantification plays a crucial role in monitoring disease progression and evaluating treatment response in multiple sclerosis (MS). We developed a 3D, multi-arm U-Net for T2 lesion segmentation, which was trained on a large, multicenter clinical trial dataset of relapsing MS. We investigated its generalization to other relapsing and primary progressive MS clinical trial datasets, and to an external dataset from the MICCAI 2016 MS lesion segmentation challenge. Additionally, we assessed the model's ability to reproduce the separation of T2 lesion volumes between treatment and control arms; and the association of baseline T2 lesion volumes with clinical disability scores compared with manual lesion annotations. The trained model achieved a mean dice coefficient of ≥ 0.66 and a lesion detection sensitivity of ≥ 0.72 across the internal test datasets. On the external test dataset, the model achieved a mean dice coefficient of 0.62, which is comparable to 0.59 from the best model in the challenge, and a lesion detection sensitivity of 0.68. Lesion detection performance was reduced for smaller lesions (≤ 30 µL, 3-10 voxels). The model successfully maintained the separation of the longitudinal changes in T2 lesion volumes between the treatment and control arms. Such tools could facilitate semi-automated MS lesion quantification; and reduce rater burden in clinical trials.


Assuntos
Fenômenos Biológicos , Esclerose Múltipla , Humanos , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Imageamento por Ressonância Magnética , Progressão da Doença , Generalização Psicológica , Recidiva
3.
Micromachines (Basel) ; 13(12)2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36557467

RESUMO

This paper describes the application of bonded magnetic abrasive powders (MAPs) in the magnetic abrasive finishing (MAF) process. In order to improve the poor finishing performance and short service life of MAPs in polishing super-hard materials, a double-stage atomization technique was used to successfully manufacture MAPs with a CBN as an abrasive phase. The prepared results show that CBN abrasives with their original structure were deeply and densely embedded on the surface of spherical MAPs. Based on the MAF process, a five-level and four-factor central composite design experiment was carried out to verify the developed MAPs polishing performance on the finishing of cemented carbide parts (864 Hv). Working gap, rotational speed, feed rate of a workpiece, and mesh number of MAP were considered as influence factors. The analysis data was used to understand different interactions of significant parameters. A regression model for predicting the change of surface roughness was obtained, and the optimal parameter combination was figured out through a solution of a quadratic equation in Design-Expert software. According to MAF results, the strong cutting ability of atomized CBN MAPs improved the surface roughness of cemented carbide by over 80% at the optimum parameters. The strong cutting ability of atomized CBN MAPs can produce good surface quality on the hard materials. The findings of this research can promote a large-scale application of MAF technology in the surface polishing of hard materials.

4.
Materials (Basel) ; 15(21)2022 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-36363020

RESUMO

In order to improve the tribological properties of Ti-6Al-4V alloy and further broaden the application scope of titanium alloy materials in the industrial field, a preparation method of a waterjet-guided high-power laser processing surface microgroove was studied. In this paper, a multifocus coupling lens was innovatively designed to replace the spherical lens in the traditional waterjet-guided laser coupling device, which avoids the gas explosion phenomenon in the coupling of the high-power laser and waterjet, and realizes the high-quality coupling of the high-power laser and water beam fiber. Then, with the microgroove morphology as the response target, the single-factor test and response surface test of the water-guided laser processing microgroove were carried out. Based on the experimental results, an approximate mathematical model of the response surface between the process parameters and the microgroove topography target was constructed, and the quantitative relationship between the waterjet-guided laser processing parameters and the target response was studied. At the same time, the optimal combination of process parameters was obtained by multiobjective optimization, so as to effectively improve the microgroove morphology. This technology provides method guidance and a decision-making reference for subsequent waterjet-guided laser processing of titanium alloy surface functional microstructures.

5.
Front Vet Sci ; 9: 981388, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36187833

RESUMO

This study aimed to screen an appropriate starter and determine the optimal fermentation process parameters to optimize the fermentation process of nutrient components and bioactive contents in pharyngitis tablet residue. This study included two experiments. In experiment I, single-factor experimental design was used to study the effects of different biological starters (cellulase preparation; Lactobacillus Plantarum and Bacillus subtilis preparation; mixture of cellulase + Lactobacillus Plantarum and Bacillus subtilis) on the nutritional values and bioactive ingredient contents in pharyngitis tablet residue. In experiment II, orthogonal design experiment was adopted to study the effects of initial water content (45, 50, and 55%), fermentation temperature (35, 37, and 40°C), and fermentation time (24, 48, and 72 h) on the changes in nutrient components, biologically activity contents, and toxin contents of the residue after optimal fermentation agent treatment. Cellulase preparation was found to be the optimal starter. The optimal fermentation conditions were: initial water content, 55%; fermentation temperature, 37°C; and fermentation time, 72 h. The contents of aflatoxin B1 and vomit toxin were in line with Chinese feed hygiene production standards. The fermentation quality of pharyngitis tablet residue can be improved by using the optimal starter and fermentation conditions.

6.
Micromachines (Basel) ; 13(9)2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-36143997

RESUMO

Due to the special manufacturing process of cobalt-chromium alloy cardiovascular stent tubes, there are serious surface defects in their inner walls, which affects the therapeutic effect after implantation. At the same time, the traditional processing technology cannot finish the inner wall of a cardiovascular stent tube. In light of the above problems, magnetic abrasive finishing (MAF) equipment for the inner wall of an ultra-fine and ultra-long cardiovascular stent tube is proposed, and MAF technology is used to improve the surface quality of its inner wall. High-performance spherical magnetic abrasive powders are used to finish the inner wall of a cobalt-chromium alloy cardiovascular stent tube with an inner diameter of 1.6 mm and an outer diameter of 1.8 mm. The effects of finishing time, tube rotational speed, feed speed of the magnetic pole, MAPs filling quantity, and MAP abrasive size on the surface roughness and material removal thickness of cobalt-chromium alloy cardiovascular stent tube are investigated. The results show that the surface roughness of the inner wall of the cobalt-chromium alloy cardiovascular stent decreases from 0.485 µm to 0.101 µm, and the material removal thickness of the defect layer is 4.3 µm. MAF technology is used to solve the problem of the poor surface quality of the inner walls of ultra-fine and ultra-long cobalt-chromium alloy cardiovascular stent tubes.

7.
Micromachines (Basel) ; 13(9)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36144071

RESUMO

In this paper, the surface roughness of SiC ceramics was investigated in laser-assisted machining (LAM) processes; machine learning was used to predict surface roughness and to optimize the process parameters, and therefore, to ultimately improve the surface quality of a workpiece and obtain excellent serviceability. First, single-factor turning experiments were carried out on SiC ceramics using LAM according to the material removal mechanism to investigate the variation trend of the effects of different laser powers, rotational speeds, feed rates, and cutting depths on surface roughness. Then, laser power, rotational speed, feed rate and cutting depth were selected as the four factors, and the surface roughness was used as the target value for the orthogonal experiments. The results of the single-factor experiments and the orthogonal experiments were combined to construct a prediction model based on the combination of the grey wolf optimization (GWO) algorithm and support vector regression (SVR). The coefficient of determination (R2) of the optimized prediction model reached 0.98676 with an average relative error of less than 2.624%. Finally, the GWO algorithm was used to optimize the global parameters of the prediction model again, and the optimal combination of process parameters was determined and verified by experiments. The actual minimum surface roughness (Ra) value was 0.418 µm, and the relative error was less than 1.91% as compared with the predicted value of the model. Therefore, the prediction model based on GWO-SVR can achieve accurate prediction of the surface roughness of SiC ceramics in LAM and can obtain the optimum surface roughness using parameter optimization.

8.
Materials (Basel) ; 15(14)2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35888357

RESUMO

In this study, laser-assisted machining experiments are carried out on silicon carbide (SiC) ceramic materials by a turning process, and laser power, cutting depth, rotational speed, and feed speed are selected as research factors. In order to improve the surface processing quality of laser-assisted turning of SiC ceramics and obtain the smallest surface roughness, the orthogonal method and response surface method are used to investigate the effect of various factors on surface roughness. The effect of various factors on surface roughness is evaluated by variance analysis, mean analysis, main effect diagram, 3D response surface, and corresponding contour diagram. The surface roughness prediction model is established based on the response surface method, and the prediction error is 4.1% with high accuracy. The experimental results show that laser power and cutting depth are the most significant factors affecting surface roughness, and rotational speed is a significant factor affecting surface roughness. Under the optimum process conditions, the smallest surface roughness Ra obtained by the response surface method is 0.294 µm, which is lower than 0.315 µm obtained by the orthogonal method, and the surface quality is higher. Therefore, the optimal process parameters of the response surface method can obtain the smallest surface roughness and higher surface quality in laser-assisted turning of SiC ceramics.

9.
Neuroimage Clin ; 34: 102959, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35189455

RESUMO

BACKGROUND: Despite advancements in treatments for multiple sclerosis, insidious disease progression remains an area of unmet medical need, for which atrophy-based biomarkers may help better characterize the progressive biology. METHODS: We developed and applied a method of longitudinal deformation-based morphometry to provide voxel-level assessments of brain volume changes and identified brain regions that were significantly impacted by disease-modifying therapy. RESULTS: Using brain MRI data from two identically designed pivotal trials of relapsing multiple sclerosis (total N = 1483), we identified multiple deep brain regions, including the thalamus and brainstem, where volume loss over time was reduced by ocrelizumab (p < 0.05), a humanized anti-CD20 + monoclonal antibody approved for the treatment of multiple sclerosis. Additionally, identified brainstem shrinkage, as well as brain ventricle expansion, was associated with a greater risk for confirmed disability progression (p < 0.05). CONCLUSIONS: The identification of deep brain structures has a strong implication for developing new biomarkers of brain atrophy reduction to advance drug development for multiple sclerosis, which has an increasing focus on targeting the progressive biology.


Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Anticorpos Monoclonais Humanizados , Atrofia , Encéfalo/diagnóstico por imagem , Humanos , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico
10.
Radiology ; 302(3): 662-673, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34904871

RESUMO

Background Deep learning-based segmentation could facilitate rapid and reproducible T1 lesion load assessments, which is crucial for disease management in multiple sclerosis (MS). T1 unenhancing and contrast-enhancing lesions in MS are those that enhance or do not enhance after administration of a gadolinium-based contrast agent at T1-weighted MRI. Purpose To develop deep learning models for automated assessment of T1 unenhancing and contrast-enhancing lesions; to investigate if joint training improved performance; to reproduce a known ocrelizumab treatment response; and to evaluate the association of baseline T1-weighted imaging metrics with clinical outcomes in relapsing MS clinical trials. Materials and Methods Joint and individual deep learning models (U-Nets) were developed retrospectively on multimodal MRI data sets from large multicenter OPERA trials of relapsing MS (August 2011 to May 2015). The joint model included cross-network connections and a combined loss function. Models were trained on OPERA I data sets with three-fold cross-validation. OPERA II data sets were the internal test set. Dice coefficients, lesion true-positive and false-positive rates, and areas under the receiver operating characteristic curve (AUCs) were used to evaluate model performance. Association of baseline imaging metrics with clinical outcomes was assessed with Cox proportional hazards models. Results A total of 796 patients (3030 visits; mean age, 37 years ± 9; 521 women) from the OPERA II trial were evaluated. The joint model achieved a mean Dice coefficient of 0.77 and 0.74, lesion true-positive rate of 0.88 and 0.86, and lesion false-positive rate of 0.04 and 0.19 for T1 contrast-enhancing and T1 unenhancing lesion segmentation, respectively. Joint training improved performance for smaller T1 contrast-enhancing lesions (≤0.06 mL; individual training AUC: 0.75; joint training AUC: 0.87; P < .001). A significant ocrelizumab treatment effect (P < .001) was seen in reducing the mean number of T1 contrast-enhancing lesions at 24, 48, and 96 weeks (manual assessment at 24 weeks: 10 lesions in 366 patients with ocrelizumab, 141 lesions in 355 patients with interferon, 93% reduction; manual assessment at 48 weeks: six lesions in 355 patients with ocrelizumab, 150 lesions in 317 patients with interferon, 96% reduction; manual assessment at 96 weeks: five lesions in 340 patients with ocrelizumab, 157 lesions in 294 patients with interferon, 97% reduction; joint model assessment at 24 weeks: 19 lesions in 365 patients with ocrelizumab, 128 lesions in 354 patients with interferon, 86% reduction; joint model assessment at 48 weeks: 14 lesions in 355 patients with ocrelizumab, 121 lesions in 317 patients with interferon, 90% reduction; joint model assessment at 96 weeks: 10 lesions in 340 patients with ocrelizumab, 144 lesions in 294 patients with interferon, 94% reduction) and the mean number of new T1 unenhancing lesions across all follow-up examinations (manual assessment: 504 lesions in 1060 visits for ocrelizumab-treated patients, 1438 lesions in 965 visits for interferon-treated patients, 68% reduction; joint model assessment: 205 lesions in 1053 visits for ocrelizumab-treated patients, 661 lesions in 957 visits for interferon-treated patients, 78% reduction). Baseline T1 unenhancing total lesion volume was associated with clinical outcomes (manual hazard ratio [HR]: 1.12, P = .02; joint model HR: 1.11, P = .03). Conclusion Joint architecture and training improved segmentation of MRI T1 contrast-enhancing multiple sclerosis lesions, and both deep learning models had sufficiently high performance to detect an ocrelizumab treatment response consistent with manual assessments. ClinicalTrials.gov: NCT01247324 and NCT01412333 © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Talbott in this issue.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Aprendizado Profundo , Imageamento por Ressonância Magnética/métodos , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/tratamento farmacológico , Adulto , Meios de Contraste , Conjuntos de Dados como Assunto , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Masculino , Estudos Retrospectivos
11.
Alzheimers Dement ; 16(4): 651-661, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32147939

RESUMO

INTRODUCTION: Both beta-amyloid (Ab) deposition and decline in white matter integrity, are brain alterations observed in Alzheimer's disease (AD) and start to occur by the fourth and fifth decades. However, the association between both brain alterations in asymptomatic subjects is unclear. METHODS: Amyloid positron emission tomography (PET) and diffusion tensor imaging (DTI) were obtained in 282 cognitively normal subjects (age 30-89 years). We assessed the interaction of age by abnormal amyloid PET status (Florbetapir F-18 PET >1.2 standard uptake value ratio [SUVR]) on regional mean diffusivity (MD) and global white matter hyperintensity (WMH) volume, controlled for sex, education, and hypertension. RESULTS: Subjects with abnormal amyloid PET (n = 87) showed stronger age-related increase in global WMH and regional MD, particularly within the posterior parietal regions of the white matter. DISCUSSION: Sporadic Aß deposition is associated with white matter alterations in AD predilection areas in an age-dependent manner in cognitively normal individuals.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Cognição/fisiologia , Voluntários Saudáveis , Longevidade , Substância Branca/metabolismo , Adulto , Idoso , Doença de Alzheimer , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons
12.
Huan Jing Ke Xue ; 40(11): 5057-5065, 2019 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854574

RESUMO

To understand the relationship between nitrogen and carbon removal performance and the microbial community during start-up of simultaneous ANAMMOX and denitrification (SAD), nitrogen and carbon removal performance and microbial community change were studied by gradually increasing the influent COD concentration. The results showed that with the increase of the influent COD concentration, NH4+-N and NO2--N effluent remained stable, and the average removal rate was more than 98%. The removal rate of TN increased gradually, and the rate was 95.6% in the third stage, which was 6.8% higher than that of ANAMMOX in theory. ΔNO3--N/ΔNH4+-N decreased significantly from 0.15-0.17 to 0.03-0.07. The contribution rate of ANAMMOX to nitrogen removal decreased gradually, denitrification for nitrogen removal increased gradually, and the COD removal rate increased. Sludge activity analysis showed that the denitrification activity of sludge increased significantly and the ANAMMOX activity decreased slightly after the start-up of SAD. High throughput sequencing results showed that the dominant phyla of microorganisms in the reactor were Chloroflexi, Planctomycetes, Firmicutes, Armatimonadetes, and Proteobacteria. The characteristics of the microbial community in the reactor were closely related to the performance of SAD in nitrogen and carbon removal. The main functional microorganisms related to nitrogen and carbon removal were ANAMMOX bacteria, anaerobic digestive bacteria, and denitrifying bacteria. The abundance of ANAMMOX bacteria decreased after the start-up of SAD, and the anaerobic digestive bacteria and heterotrophic denitrifying bacteria increased significantly.


Assuntos
Desnitrificação , Microbiota , Reatores Biológicos , Nitrogênio , Oxirredução , Esgotos
13.
Neurobiol Aging ; 68: 114-122, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29602495

RESUMO

The fornix and parahippocampal cingulum are 2 major limbic tracts in the core memory network of the hippocampus. Although these fiber tracts are known to degrade with Alzheimer's disease (AD), little is known about their vulnerability in the asymptomatic phase of AD. In this longitudinal study of cognitively normal adults, we assessed amyloid-beta (Aß) plaques using positron emission tomography and white matter microstructure using diffusion tensor imaging. We found that an increase of neocortical Aß burden over time was associated with an increase of radial diffusivity in the fornix but not in the parahippocampal cingulum. The effect of increasing neocortical Aß burden on the fornix remained significant after controlling for baseline measures, head motion, global brain atrophy, regional Aß burden in the hippocampus, or microstructural changes in the global white matter. In addition, microstructural changes in the fornix were not associated with decline of episodic memory or other cognitive abilities. Our findings suggest that microstructural changes in the fornix may be an early sign in the asymptomatic phase of AD.


Assuntos
Envelhecimento/metabolismo , Envelhecimento/patologia , Peptídeos beta-Amiloides/metabolismo , Cognição , Fórnice/metabolismo , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/psicologia , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Imagem de Tensor de Difusão , Diagnóstico Precoce , Feminino , Fórnice/diagnóstico por imagem , Fórnice/patologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Substância Branca/diagnóstico por imagem , Substância Branca/metabolismo , Substância Branca/patologia
14.
Eur J Med Chem ; 124: 809-819, 2016 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-27643639

RESUMO

A novel class of (2E)-(2-oxo-1, 2-dihydro-3H-indol-3-ylidene)acetate derivatives were designed and synthesized as potent anti-proliferative agents. Most of these compounds showed potent anti-proliferative activity against some tumor cell lines, including SK-BR-3, MDA-MB-231, HCT-116, SW480, Ovcar-3, HL-60, Saos-2 and HepG2. Compounds 8c and 11h were identified as the most potent ones, while HL-60, HCT116 and MDA-MB-231 were the most sensitive cell lines. Mechanistic study revealed that compound 8c enhanced reactive oxygen species level by inhibiting TrxR and then induced apoptosis by activating apoptosis proteins, bax and cleaved-caspase 3 in HCT116 cells. Preliminary SAR analysis indicated that modifications of the double bond and ester group made great effects on the anti-proliferative activity. Our findings suggested that it was worth further studies on the antitumor potency of (2E)-(2-oxo-1, 2-dihydro-3H-indol-3-ylidene)acetates.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Desenho de Fármacos , Indóis/síntese química , Indóis/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos/química , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Técnicas de Química Sintética , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Indóis/química , Relação Estrutura-Atividade , Tiorredoxina Dissulfeto Redutase/antagonistas & inibidores
15.
Neuroimage Clin ; 12: 78-84, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27408792

RESUMO

Neurodegeneration in the medial temporal lobe, particularly in the hippocampus, is viewed as the primary source of AD-related memory deficits. Yet, in the earliest preclinical phase of Alzheimer's disease (AD), amyloid-beta (Aß) plaques deposit primarily in the neocortex, not in the medial temporal lobe. Tau tangles, however, do often aggregate in the medial temporal lobe in parallel with amyloid deposition in the neocortex in AD. In the present study, we focused on the relationship between cortical amyloid deposition and hippocampal activity during a memory-encoding task in a sample of cognitively-normal elderly aged 60-89. We hypothesized that age would moderate the Aß effect on hippocampal activity, and could explain some of the mixed findings in the literature. We report that high cortical Aß load was associated with lower task-related hippocampal activity during memory encoding. Importantly, this relationship was found more evident in the younger elderly, even after controlling for subsequent recognition memory of the in-scanner task and a general episodic memory construct score. Furthermore, regional cerebrovascular reactivity measured in a subset of participants showed little role in modifying the age-dependent Aß effect on hippocampal activity. Our findings support the idea that age is an important variable in understanding hippocampal function in preclinical AD.


Assuntos
Envelhecimento/fisiologia , Doença de Alzheimer , Peptídeos beta-Amiloides/metabolismo , Córtex Cerebral/metabolismo , Hipocampo/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/metabolismo , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Sintomas Prodrômicos
16.
Chem Commun (Camb) ; 52(36): 6079-82, 2016 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-27087623

RESUMO

The Rh(ii)-catalyzed sulfur ylide [1,2]-rearrangement of carbenoids generated from aryldiazoacetates has been realized via N-S bond insertion, generating tertiary sulfides in moderate to excellent yields. This demonstrates the first use of the sulfur ylide [1,2]-rearrangement undergoing N-S bond insertion. This protocol could proceed smoothly with high regioselectivity, low catalyst loading (0.1 mol% Rh2(OAc)4), gram-scale reaction and broad substrate scope. And the product could be converted into glycine derivatives through simple procedures.

17.
Magn Reson Med ; 75(1): 433-40, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25733066

RESUMO

PURPOSE: To accelerate denoising of magnitude diffusion-weighted images subject to joint rank and edge constraints. METHODS: We extend a previously proposed majorize-minimize method for statistical estimation that involves noncentral χ distributions to incorporate joint rank and edge constraints. A new algorithm is derived which decomposes the constrained noncentral χ denoising problem into a series of constrained Gaussian denoising problems each of which is then solved using an efficient alternating minimization scheme. RESULTS: The performance of the proposed algorithm has been evaluated using both simulated and experimental data. Results from simulations based on ex vivo data show that the new algorithm achieves about a factor of 10 speed up over the original Quasi-Newton-based algorithm. This improvement in computational efficiency enabled denoising of large datasets containing many diffusion-encoding directions. The denoising performance of the new efficient algorithm is found to be comparable to or even better than that of the original slow algorithm. For an in vivo high-resolution Q-ball acquisition, comparison of fiber tracking results around hippocampus region before and after denoising will also be shown to demonstrate the denoising effects of the new algorithm. CONCLUSION: The optimization problem associated with denoising noncentral χ distributed diffusion-weighted images subject to joint rank and edge constraints can be solved efficiently using a majorize-minimize-based algorithm.


Assuntos
Algoritmos , Artefatos , Encéfalo/anatomia & histologia , Imagem de Difusão por Ressonância Magnética/métodos , Aumento da Imagem/métodos , Imageamento Tridimensional/métodos , Animais , Simulação por Computador , Interpretação de Imagem Assistida por Computador/métodos , Técnicas In Vitro , Modelos Estatísticos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Razão Sinal-Ruído , Suínos
18.
J Org Chem ; 80(9): 4459-64, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25818727

RESUMO

A practical and efficient stereoselective synthesis of arylglycine derivatives was realized via palladium-catalyzed α-arylation of a chiral nickel(II) glycinate complex with aryl bromides. The structurally diverse arylglycine products were obtained in excellent isolated yields and with good diastereoselectivity. A simple acidic hydrolysis furnished optically pure arylglycines in high yield, and the chiral ligand (S)-BPB could be efficiently recovered and reused.


Assuntos
Glicina/síntese química , Níquel/química , Compostos Organometálicos/química , Paládio/química , Catálise , Glicina/análogos & derivados , Glicina/química , Conformação Molecular , Estereoisomerismo
19.
J Neurosci ; 35(7): 3240-7, 2015 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-25698758

RESUMO

The medial temporal lobe is implicated as a key brain region involved in the pathogenesis of Alzheimer's disease (AD) and consequent memory loss. Tau tangle aggregation in this region may develop concurrently with cortical Aß deposition in preclinical AD, but the pathological relationship between tau and Aß remains unclear. We used task-free fMRI with a focus on the medical temporal lobe, together with Aß PET imaging, in cognitively normal elderly human participants. We found that cortical Aß load was related to disrupted intrinsic functional connectivity of the perirhinal cortex, which is typically the first brain region affected by tauopathies in AD. There was no concurrent association of cortical Aß load with cognitive performance or brain atrophy. These findings suggest that dysfunction in the medial temporal lobe may represent a very early sign of preclinical AD and may predict future memory loss.


Assuntos
Envelhecimento/patologia , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Lobo Temporal/irrigação sanguínea , Lobo Temporal/diagnóstico por imagem , Idoso , Mapeamento Encefálico , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Oxigênio/sangue , Tomografia por Emissão de Pósitrons
20.
Bing Du Xue Bao ; 29(4): 426-31, 2013 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-23895009

RESUMO

To study on the molecular evolution of Coxsackie virus A16 (CVA16)isolated from clinical speci-mens of Hand, foot and mouth Disease( HFMD) patients in Inner Mongolia in 2010. A total of 921 clinical specimens including stools, throat swabs and vesicle fluids were collected from 888 HFMD patients in out-patient service in Inner Mongolia and viral isolation was then performed, the positive viral isolates were identified by using the real-time PCR method detecting CVA16. A total of 50 CVA16 isolates were selected from the patients presenting mild symptoms, severe symptoms and the death patients randomly, and the VP1 coding regions of representative CVA16 isolates were amplified and sequenced. Finally the phylogenetic tree was constructed among the VP1 coding regions of the different genotypes and subgenotypes of CVA16 strains. Eighty two viruses were isolated form 921 clinical specimens, the positive rate was 8. 90%, of which 3 viruses were isolated from severe cases and 1 viruses was from death cases. The nucleotide acid of 50 representative CVA16 strains in Inner Mongolia were closed to CVA16 strains isolated from mainland China since 1998, especially from Beijing in 2009 and from Henan in 2010, the identity were 96. 18% approximately 98. 88% and 94. 94a approximately 98. 76%, respectively. There was a little difference in the nucleotide acid between the CVA16 strains from Inner Mongolia in 2010 and in 2007, the identity were 91. 68% approximately 96. 52% The phylogenetic tree showed that all CVA16 strains clustered within Bla and B1b evolution branch of B1 genotype. There was slight difference in the nucleotide and the amino acid in VP1 region among the 50 Inner Mongolia CVA16 strains, the identity were 89. 99% approximately 100% and 98. 31% approximately 100%, respectively, indicating that these strains belonged to many different viral transmission chains. The CVA16 strains circulated in Inner Mongolia in 2010 were all belong to B1a and B1b evolution branch of B1 genotype, and the two evolutionary branchs of Coxsackie virus A16 were co-evolved and co-prevailed in Inner Mongolia Autonomous Region.


Assuntos
Proteínas do Capsídeo/genética , Infecções por Coxsackievirus/virologia , Enterovirus/isolamento & purificação , Doença de Mão, Pé e Boca/virologia , Adolescente , Adulto , Animais , Linhagem Celular Tumoral , Criança , Pré-Escolar , China/epidemiologia , Chlorocebus aethiops , Infecções por Coxsackievirus/epidemiologia , Infecções por Coxsackievirus/mortalidade , Enterovirus/classificação , Enterovirus/genética , Evolução Molecular , Fezes/virologia , Feminino , Genótipo , Doença de Mão, Pé e Boca/epidemiologia , Doença de Mão, Pé e Boca/mortalidade , Humanos , Lactente , Masculino , Filogenia , RNA Viral/genética , Análise de Sequência de DNA , Células Vero , Adulto Jovem
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