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1.
Artigo em Inglês | MEDLINE | ID: mdl-38652399

RESUMO

To enhance M-mode echocardiography's utility for measuring cardiac structures, we developed and evaluated an artificial intelligence (AI)-based automated analysis system for M-mode images through the aorta and left atrium [M-mode (Ao-LA)], and through the left ventricle [M-mode (LV)]. Our system, integrating two deep neural networks (DNN) for view classification and image segmentation, alongside an auto-measurement algorithm, was developed using 5,958 M-mode images [3,258 M-mode (LA-Ao), and 2,700 M-mode (LV)] drawn from a nationwide echocardiographic dataset collated from five tertiary hospitals. The performance of view classification and segmentation DNNs were evaluated on 594 M-mode images, while automatic measurement accuracy was tested on separate internal test set with 100 M-mode images as well as external test set with 280 images (140 sinus rhythm and 140 atrial fibrillation). Performance evaluation showed the view classification DNN's overall accuracy of 99.8% and segmentation DNN's Dice similarity coefficient of 94.3%. Within the internal test set, all automated measurements, including LA, Ao, and LV wall and cavity, resonated strongly with expert evaluations, exhibiting Pearson's correlation coefficients (PCCs) of 0.81-0.99. This performance persisted in the external test set for both sinus rhythm (PCC, 0.84-0.98) and atrial fibrillation (PCC, 0.70-0.97). Notably, automatic measurements, consistently offering multi-cardiac cycle readings, showcased a stronger correlation with the averaged multi-cycle manual measurements than with those of a single representative cycle. Our AI-based system for automatic M-mode echocardiographic analysis demonstrated excellent accuracy, reproducibility, and speed. This automated approach has the potential to improve efficiency and reduce variability in clinical practice.

2.
J Biomech ; 168: 112059, 2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38631187

RESUMO

The progression of cardiovascular disease is intricately influenced by a complex interplay between physiological pathways, biochemical processes, and physical mechanisms. This study aimed to develop an in-silico physics-based approach to comprehensively model the multifaceted vascular pathophysiological adaptations. This approach focused on capturing the progression of proximal pulmonary arterial hypertension, which is significantly associated with the irreversible degradation of arterial walls and compensatory stress-induced growth and remodeling. This study incorporated critical characteristics related to the distinct time scales for the deformation, thus reflecting the impact of mean pressure on artery growth and tissue damage. The in-silico simulation of the progression of pulmonary hypertension was realized based on computational code combined with the finite element method (FEM) for the simulation of disease progression. The parametric studies further explored the consequences of these irreversible processes. This computational modeling approach may advance our understanding of pulmonary hypertension and its progression.

3.
Yonsei Med J ; 65(5): 257-264, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38653564

RESUMO

PURPOSE: In a preclinical study using a swine myocardial infarction (MI) model, a delayed enhancement (DE)-multi-detector computed tomography (MDCT) scan was performed using a hybrid system alongside diagnostic invasive coronary angiography (ICA) without the additional use of a contrast agent, and demonstrated an excellent correlation in the infarct area compared with histopathologic specimens. In the present investigation, we evaluated the feasibility and diagnostic accuracy of a myocardial viability assessment by DE-MDCT using a hybrid system comprising ICA and MDCT alongside diagnostic ICA without the additional use of a contrast agent. MATERIALS AND METHODS: We prospectively enrolled 13 patients (median age: 67 years) with a previous MI (>6 months) scheduled to undergo ICA. All patients underwent cardiac magnetic resonance (CMR) imaging before diagnostic ICA. MDCT viability scans were performed concurrently with diagnostic ICA without the use of additional contrast. The total myocardial scar volume per patient and average transmurality per myocardial segment measured by DE-MDCT were compared with those from DE-CMR. RESULTS: The DE volume measured by MDCT showed an excellent correlation with the volume measured by CMR (r=0.986, p<0.0001). The transmurality per segment by MDCT was well-correlated with CMR (r=0.900, p<0.0001); the diagnostic performance of MDCT in differentiating non-viable from viable myocardium using a 50% transmurality criterion was good with a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 87.5%, 99.5%, 87.5%, 99.5%, and 99.1%, respectively. CONCLUSION: The feasibility of the DE-MDCT viability assessment acquired simultaneously with conventional ICA was proven in patients with chronic MI using DE-CMR as the reference standard.


Assuntos
Angiografia Coronária , Infarto do Miocárdio , Humanos , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/patologia , Idoso , Angiografia Coronária/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Tomografia Computadorizada Multidetectores/métodos
4.
J Thorac Imaging ; 39(2): 119-126, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37889556

RESUMO

PURPOSE: To evaluate the ability of radiomics score (RS)-based machine learning to identify moderate to severe coronary artery calcium (CAC) on chest x-ray radiographs (CXR). MATERIALS AND METHODS: We included 559 patients who underwent a CAC scan with CXR obtained within 6 months and divided them into training (n = 391) and validation (n = 168) cohorts. We extracted radiomic features from annotated cardiac contours in the CXR images and developed an RS through feature selection with the least absolute shrinkage and selection operator regression in the training cohort. We evaluated the incremental value of the RS in predicting CAC scores when combined with basic clinical factor in the validation cohort. To predict a CAC score ≥100, we built an RS-based machine learning model using random forest; the input variables were age, sex, body mass index, and RS. RESULTS: The RS was the most prominent factor for the CAC score ≥100 predictions (odds ratio = 2.33; 95% confidence interval: 1.62-3.44; P < 0.001) compared with basic clinical factor. The machine learning model was tested in the validation cohort and showed an area under the receiver operating characteristic curve of 0.808 (95% confidence interval: 0.75-0.87) for a CAC score ≥100 predictions. CONCLUSIONS: The use of an RS-based machine learning model may have the potential as an imaging marker to screen patients with moderate to severe CAC scores before diagnostic imaging tests, and it may improve the pretest probability of detecting coronary artery disease in clinical practice.


Assuntos
Doença da Artéria Coronariana , Humanos , Doença da Artéria Coronariana/diagnóstico por imagem , Raios X , Valor Preditivo dos Testes , Aprendizado de Máquina , Estudos Retrospectivos
5.
Adv Sci (Weinh) ; 10(33): e2303308, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37867236

RESUMO

Argyrodite-type Li6 PS5 Cl (LPSCl) has attracted much attention as a solid electrolyte for all-solid-state batteries (ASSBs) because of its high ionic conductivity and good mechanical flexibility. LPSCl, however, has challenges of translating research into practical applications, such as irreversible electrochemical degradation at the interface between LPSCl and cathode materials. Even for Li-ion batteries (LIBs), liquid electrolytes have the same issue as electrolyte decomposition due to interfacial instability. Nonetheless, current LIBs are successfully commercialized because functional electrolyte additives give rise to the formation of stable cathode-electrolyte interphase (CEI) and solid-electrolyte interphase (SEI) layers, leading to supplementing the interfacial stability between electrolyte and electrode. Herein, inspired by the role of electrolyte additives for LIBs, trimethylsilyl compounds are introduced as solid electrolyte additives for improving the interfacial stability between sulfide-based solid electrolytes and cathode materials. 2-(Trimethylsilyl)ethanethiol (TMS-SH), a solid electrolyte additive, is oxidatively decomposed during charge, forming a stable CEI layer. As a result, the CEI layer derived from TMS-SH suppresses the interfacial degradation between LPSCl and LiCoO2 , thereby leading to the excellent electrochemical performance of Li | LPSCl | LiCoO2 , such as superior cycle life over 2000 cycles (85.0% of capacity retention after 2000 cycles).

6.
Adv Sci (Weinh) ; 10(33): e2304979, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37811768

RESUMO

Monitoring and diagnosing the battery status in real-time are of utmost importance for clarifying failure mechanism, improving battery performance, and ensuring safety, particularly under fast charging conditions. Recently, advanced operando techniques have been developed to observe changes in the microstructures of lithium deposits using laboratory-scale cell designs, focusing on understanding the nature of Li metal electrodes. However, the macroscopic spatial inhomogeneity of lithium electroplating/stripping in the prototype pressurized pouch cells has not been measured in real-time under practical conditions. Herein, a new noninvasive operando technique, spatial pressure mapping analysis, is introduced to macroscopically and quantitatively measure spatial pressure changes in a pressurized pouch cell during cycling. Moreover, dynamic spatial changes in the macroscopic morphology of the lithium metal electrode are theoretically visualized by combining operando pressure mapping data with mechanical analyses of cell components. Additionally, under fast charging conditions, the direct correlation between abrupt capacity fading and sudden increases in spatial pressure distribution inhomogeneity is demonstrated through comparative analysis of pouch cells under various external pressures, electrolyte species, and electrolyte weight to cell capacity (e/c) ratios. This operando technique provides insights for assessing the current battery status and understanding the complex origin of cell degradation behavior in pressurized pouch cells.

7.
Molecules ; 28(7)2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-37049874

RESUMO

Recently, semiconductor wastewater treatment has received much attention due to the emergence of environmental issues. Acid-resistant coatings are essential for metal prefilters used in semiconductor wastewater treatment. Perfluoroalkoxy alkane is mainly used as an acid-resistant coating agent, since PFA has inherent superhydrophobicity, water permeability is lowered. To solve this problem, the surface of the PFA-coated metal mesh was treated via an oxyfluorination method in which an injected mixed gas of fluorine and oxygen reacted with the surface functional groups. Surface analysis, water contact angle measurement, and water permeability tests were performed on the surface-treated PFA-coated mesh. Consequently, the superhydrophobic surface was effectively converted to a hydrophobic surface as the PFA coating layer was surface-modified with C-O-OH functional groups via the oxyfluorination reaction. As a result of using simulation solutions that float silica particles of various sizes, the permeability and particle removal rate of the surface-modified PFA-coated stainless-steel mesh were improved compared to those before surface modification. Therefore, the oxyfluorination treatment used in this study was suitable for improving the filtration performance of SiO2 microparticles in the PFA-coated stainless-steel mesh.

8.
Nanomaterials (Basel) ; 13(6)2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36985889

RESUMO

In this study, multi-walled carbon nanotubes (MWCNTs) were modified by thermal fluorination to improve dispersibility between MWCNTs and Li4Ti5O12 (LTO) and were used as additives to compensate for the disadvantages of LTO anode materials with low electronic conductivity. The degree of fluorination of the MWCNTs was controlled by modifying the reaction time at constant fluorination temperature; the clear structure and surface functional group changes in the MWCNTs due to the degree of fluorination were determined. In addition, the homogeneous dispersion in the LTO was improved due to the strong electronegativity of fluorine. The F-MWCNT conductive additive was shown to exhibit an excellent electrochemical performance as an anode for lithium ion batteries (LIBs). In particular, the optimized LTO with added fluorinated MWCNTs not only exhibited a high specific capacity of 104.8 mAh g-1 at 15.0 C but also maintained a capacity of ~116.8 mAh g-1 at a high rate of 10.0 C, showing a capacity almost 1.4 times higher than that of LTO with the addition of pristine MWCNTs and an improvement in the electrical conductivity. These results can be ascribed to the fact that the semi-ionic C-F bond of the fluorinated MWCNTs reacts with the Li metal during the charge/discharge process to form LiF, and the fluorinated MWCNTs are converted into MWCNTs to increase the conductivity due to the bridge effect of the conductive additive, carbon black, with LTO.

9.
Pharmaceuticals (Basel) ; 15(6)2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35745670

RESUMO

Here, we describe the synthesis, characterization, and in vitro biological evaluation of a series of transition metal complexes containing benzothiazole aniline (BTA). We employed BTA, which is known for its selective anticancer activity, and a salen-type Schiff-based ligand to coordinate several transition metals to achieve selective and synergistic cytotoxicity. The compounds obtained were characterized by NMR spectroscopy, mass spectrometry, Fourier transform infrared spectroscopy, and elemental analysis. The compounds L, MnL, FeL, CoL, and ZnL showed promising in vitro cytotoxicity against cancer cells, and they had a lower IC50 than that of the clinically used cisplatin. In particular, MnL had synergistic cytotoxicity against liver, breast, and colon cancer cells. Moreover, MnL, CoL, and CuL promoted the production of reactive oxygen species in HepG2 tumor cell lines. The lead compound of this series, MnL, remained stable in physiological settings, and docking results showed that it interacted rationally with the minor groove of DNA. Therefore, MnL may serve as a viable alternative to platinum-based chemotherapy.

10.
J Org Chem ; 87(13): 8380-8389, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35731897

RESUMO

C(aryl)-OMe bond functionalization catalyzed by cobalt(II) chloride in combination with a nacnac-type ligand and magnesium as a reductant is reported. Borylation and benzoylation of aryl methoxides are demonstrated, and C(aryl)-SMe bond borylation can be achieved under similar conditions. This is the first example of achieving these transformations using cobalt catalysis. Mechanistic studies suggest that a Grignard reagent is generated as an intermediate in a rare example of a magnesiation via a C-O bond activation reaction. Indeed, an organomagnesium species could be directly observed by electrospray ionization mass spectroscopic analysis. Kinetic experiments indicate that a heterogeneous cobalt catalyst performs the C-O bond activation.

11.
Cancers (Basel) ; 14(8)2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35454900

RESUMO

Hepatocellular carcinomas (HCCs) are aggressive tumors with a poor prognosis. Approved first-line treatments include sorafenib, lenvatinib, and a combination of atezolizumab and bevacizumab; however, they do not cure HCC. We investigated MBP-11901 as a drug candidate for HCC. Cell proliferation and cytotoxicity were evaluated using normal and cancer human liver cell lines, while Western blotting and flow cytometry evaluated apoptosis. The anticancer effect of MBP-11901 was verified in vitro through migration, invasion, colony formation, and JC-1 MMP assays. In mouse models, the tumor volume, tumor weight, and bodyweight were measured, and cancer cell proliferation and apoptosis were analyzed. The toxicity of MBP-11901 was investigated through GOT/GPT and histological analyses in the liver and kidney. The signaling mechanism of MBP-11901 was investigated through kinase assays, phosphorylation analysis, and in silico docking simulations. Results. MBP-11901 was effective against various human HCC cell lines, leading to the disappearance of most tumors when administered orally in animal models. This effect was dose-dependent, with no differences in efficacy according to administration intervals. MBP-11901 induced anticancer effects by targeting the signaling mechanisms of FLT3, VEGFR2, c-KIT, and PDGFRß. MBP-11901 is suggested as a novel therapeutic agent for the treatment of advanced or unresectable liver cancer.

12.
Pharmaceuticals (Basel) ; 14(8)2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34451928

RESUMO

We describe the synthesis, characterization, molecular modeling, and in vitro anticancer activity of three benzothiazole aniline (BTA) ligands and their corresponding platinum (II) complexes. We designed the compounds based on the selective antitumor properties of BTA, along with three types of metallic centers, aiming to take advantage of the distinctive and synergistic activity of the complexes to develop anticancer agents. The compounds were characterized using nuclear magnetic resonance spectrometry, Fourier transform infrared spectroscopy, mass spectrometry, elemental analysis, and tested for antiproliferative activity against multiple normal and cancerous cell lines. L1, L2, and L1Pt had better cytotoxicity in the liver, breast, lung, prostate, kidney, and brain cells than clinically used cisplatin. Especially, L1 and L1Pt demonstrated selective inhibitory activities against liver cancer cells. Therefore, these compounds can be a promising alternative to the present chemotherapy drugs.

13.
Yonsei Med J ; 62(3): 200-208, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33635009

RESUMO

PURPOSE: To compare image quality in selective intracoronary contrast-injected computed tomography angiography (Selective-CTA) with that in conventional intravenous contrast-injected CTA (IV-CTA). MATERIALS AND METHODS: Six pigs (35 to 40 kg) underwent both IV-CTA using an intravenous injection (60 mL) and Selective-CTA using an intracoronary injection (20 mL) through a guide-wire during/after percutaneous coronary intervention. Images of the common coronary artery were acquired. Scans were performed using a combined machine comprising an invasive coronary angiography suite and a 320-channel multi-slice CT scanner. Quantitative image quality parameters of CT attenuation, image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), mean lumen diameter (MLD), and mean lumen area (MLA) were measured and compared. Qualitative analysis was performed using intraclass correlation coefficient (ICC), which was calculated for analysis of interobserver agreement. RESULTS: Quantitative image quality, determined by assessing the uniformity of CT attenuation (399.06 vs. 330.21, p<0.001), image noise (24.93 vs. 18.43, p<0.001), SNR (16.43 vs. 18.52, p=0.005), and CNR (11.56 vs. 13.46, p=0.002), differed significantly between IV-CTA and Selective-CTA. MLD and MLA showed no significant difference overall (2.38 vs. 2.44, p=0.068, 4.72 vs. 4.95, p=0.078). The density of contrast agent was significantly lower for selective-CTA (13.13 mg/mL) than for IV-CTA (400 mg/mL). Agreement between observers was acceptable (ICC=0.79±0.08). CONCLUSION: Our feasibility study in swine showed that compared to IV-CTA, Selective-CTA provides better image quality and requires less iodine contrast medium.


Assuntos
Angiografia por Tomografia Computadorizada , Meios de Contraste/química , Angiografia Coronária , Aumento da Imagem , Animais , Vasos Coronários , Estudos de Viabilidade , Feminino , Processamento de Imagem Assistida por Computador , Doses de Radiação , Suínos
14.
Sci Rep ; 10(1): 16741, 2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028868

RESUMO

It is recently suggested that amyloid polymorphism, i.e., structural diversity of amyloid fibrils, has a deep relationship with pathology. However, its prompt recognition is almost halted due to insufficiency of analytical methods for detecting polymorphism of amyloid fibrils sensitively and quickly. Here, we propose that iodine staining, a historically known reaction that was firstly found by Virchow, can be used as a method for distinguishing amyloid polymorphs. When insulin fibrils were prepared and iodine-stained, they exhibited different colors depending on polymorphs. Each of the colors was inherited to daughter fibrils by seeding reactions. The colors were fundamentally represented as a sum of three absorption bands in visible region between 400 and 750 nm, and the bands showed different titration curves against iodine, suggesting that there are three specific iodine binding sites. The analysis of resonance Raman spectra and polarization microscope suggested that several polyiodide ions composed of I3- and/or I5- were formed on the grooves or the edges of ß-sheets. It was concluded that the polyiodide species and conformations formed are sensitive to surface structure of amyloid fibrils, and the resultant differences in color will be useful for detecting polymorphism in a wide range of diagnostic samples.


Assuntos
Amiloide/metabolismo , Insulina/metabolismo , Iodo , Humanos , Coloração e Rotulagem
15.
Biochim Biophys Acta Proteins Proteom ; 1868(6): 140410, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32169581

RESUMO

Isomerization of aspartate (Asp) is a common non-enzymatic posttranslational modification. Isomerized residues accumulate in proteins associated with age-related human disorders such as cataract and are well known to affect protein structure and function. We previously detected d-Asp-containing peptides in human serum. In this study, we investigated whether isomerized Asp residues are present in human immunoglobulin G (IgG) kappa chain by a qualitative d-amino acid analysis based on diastereomer formation and liquid chromatography tandem mass spectrometry (LC-MS/MS). We also investigated the d/l ratio of Asp residues in the IgG kappa chain in serum from donors aged 25, 37, 41, 54 and 67 years. As a result, two isomerized Asp residues, Asp151 and Asp170, were detected in the IgG kappa chain, and the d/l ratio of these residues was found to increase with aging. To assess the effects of this isomerization, we synthesized four isomeric peptides of IgG kappa chain containing lα-, lß-, dα-, or dß-Asp at position 170, and compared their secondary structures by CD spectroscopy. Peptide containing normal lα-Asp170 showed type II ß-turn structure, while the other isomeric peptides showed random structure, clearly indicating that substitution of a single Asp isomer alters the secondary structure of the peptide. Because IgG is a main component of humoral immunity, Asp isomerization in IgG may reflect changes of structure and decrease in immune function. Proteome research on serum from the standpoint of racemization might enable us to develop new kinds of biomarker and new directions to study the aging process.


Assuntos
Envelhecimento/metabolismo , Ácido Aspártico/química , Imunoglobulina G/química , Fatores Imunológicos/química , Adulto , Idoso , Biomarcadores , Catarata/metabolismo , Cromatografia Líquida/métodos , Humanos , Imunoglobulina G/metabolismo , Cadeias kappa de Imunoglobulina , Isomerismo , Pessoa de Meia-Idade , Modelos Moleculares , Peptídeos/química , Processamento de Proteína Pós-Traducional , Proteoma , Soro , Estereoisomerismo , Espectrometria de Massas em Tandem/métodos
16.
Yonsei Med J ; 61(2): 137-144, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31997622

RESUMO

PURPOSE: To evaluate the diagnostic accuracy of a novel on-site virtual fractional flow reserve (vFFR) derived from coronary computed tomography angiography (CTA). MATERIALS AND METHODS: We analyzed 100 vessels from 57 patients who had undergone CTA followed by invasive FFR during coronary angiography. Coronary lumen segmentation and three-dimensional reconstruction were conducted using a completely automated algorithm, and parallel computing based vFFR prediction was performed. Lesion-specific ischemia based on FFR was defined as significant at ≤0.8, as well as ≤0.75, and obstructive CTA stenosis was defined that ≥50%. The diagnostic performance of vFFR was compared to invasive FFR at both ≤0.8 and ≤0.75. RESULTS: The average computation time was 12 minutes per patient. The correlation coefficient (r) between vFFR and invasive FFR was 0.75 [95% confidence interval (CI) 0.65 to 0.83], and Bland-Altman analysis showed a mean bias of 0.005 (95% CI -0.011 to 0.021) with 95% limits of agreement of -0.16 to 0.17 between vFFR and FFR. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 78.0%, 87.1%, 72.5%, 58.7%, and 92.6%, respectively, using the FFR cutoff of 0.80. They were 87.0%, 95.0%, 80.0%, 54.3%, and 98.5%, respectively, with the FFR cutoff of 0.75. The area under the receiver-operating characteristics curve of vFFR versus obstructive CTA stenosis was 0.88 versus 0.61 for the FFR cutoff of 0.80, respectively; it was 0.94 versus 0.62 for the FFR cutoff of 0.75. CONCLUSION: Our novel, fully automated, on-site vFFR technology showed excellent diagnostic performance for the detection of lesion-specific ischemia.


Assuntos
Simulação por Computador , Reserva Fracionada de Fluxo Miocárdico , Idoso , Algoritmos , Área Sob a Curva , Feminino , Humanos , Modelos Lineares , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
17.
Protein Sci ; 29(4): 955-965, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31930615

RESUMO

Recent studies have suggested that the isomerization/racemization of aspartate residues in proteins increases in aged tissues. One such residue is Asp151 in lens-specific αA-crystallin. Although many isomerization/racemization sites have been reported in various proteins, the factors that lead to those modifications in proteins in vivo remain obscure. Therefore, an in vitro system is needed to assess the mechanisms of modifications of Asp under various conditions. Deamidation of Asn to Asp in proteins occurs more rapidly than isomerization/racemization of Asp, although the reaction passes through the same intermediate in both pathways. Here, therefore, we replaced Asp151 in human lens αA-crystallin with Asn by using site-directed mutagenesis. The recombinant protein was expressed in Escherichia coli and used to investigate the deamidation/isomerization/racemization of Asn151 after incubation at 50°C for various durations and under different pH. After incubation, the mutant αA-crystallin was subjected to enzymatic digestion followed by liquid chromatography-MS/MS to evaluate the ratio of modifications in Asn151-containing peptides. The Asp151Asn αA-crystallin mutant showed rapid deamidation to Asp with the formation of specific Asp isomers. In particular, deamidation increased greatly under basic conditions. By contrast, subunit-subunit interactions between αA-crystallin and αB-crystallin had little effect on the modification of Asn151. Our findings suggest that the Asp151Asn αA-crystallin mutant represents a good in vitro model protein to assess deamidation, isomerization, and the racemization intermediates. Furthermore, our in vitro results show a different trend from in vivo data, implying the presence of specific factors that induce racemization from L-Asp to D-Asp residues in vivo.


Assuntos
Cristalino/química , Asparagina/química , Asparagina/genética , Ácido Aspártico/química , Ácido Aspártico/genética , Humanos , Conformação Molecular , Mutagênese Sítio-Dirigida , Estereoisomerismo
18.
Eur Radiol ; 29(5): 2218-2225, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30421011

RESUMO

OBJECTIVE: This study aimed to evaluate the clinical feasibility of catheter-directed selective computed tomography angiography (S-CTA) in patients with coronary artery disease (CAD). METHODS: We prospectively enrolled 65 patients diagnosed with CAD who underwent conventional computed tomography angiography (C-CTA). C-CTA was performed with 60-90 mL of contrast medium (370 mg iodine/mL), whereas S-CTA was performed with 15 mL of contrast medium and 17.19 mg iodine/mL. Luminal enhancement range, homogeneity of luminal enhancement, image quality, plaque volume (PV), and percent aggregate plaque volume (%APV) were measured. Paired Student's t test, Wilcoxon rank-sum test, and Pearson's correlation coefficient were used to compare two methods. RESULTS: Luminal enhancement was significantly higher on S-CTA than on C-CTA (324.4 ± 8.0 Hounsfield unit (HU) vs. 312.0 ± 8.0 HU, p < 0.0001 in the per-vessel analysis). Transluminal attenuation gradient showed a significantly slower reduction pattern on S-CTA than on C-CTA (-0.65 HU/10 mm vs. -0.89 HU/10 mm, p < 0.0001 in the per-vessel analysis). Image noise was significantly lower on S-CTA than on C-CTA (39.6 ± 10.0 HU vs. 43.9 ± 9.4 HU, p < 0.0001). There was excellent correlation between S-CTA and C-CTA with respect to PV and %APV (r = 0.99, r = 0.98, respectively). CONCLUSIONS: S-CTA might be useful in facilitating atherosclerotic plaque analysis and providing guidance for complex lesions such as chronic total occlusion, particularly in cases in which on-site procedure planning is required. KEY POINTS: • Selective computed tomography angiography (S-CTA) can serve as an intraprocedural computed tomography angiography protocol. • S-CTA was performed with low dose of iodine compared with conventional computed tomography angiography. • S-CTA enables on-site atherosclerotic plaque analysis.


Assuntos
Cateterismo Cardíaco/métodos , Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico , Iodo/administração & dosagem , Placa Aterosclerótica/diagnóstico , Meios de Contraste/administração & dosagem , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
ACS Nano ; 12(5): 4419-4430, 2018 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-29714999

RESUMO

Lithium-oxygen (Li-O2) batteries are desirable for electric vehicles because of their high energy density. Li dendrite growth and severe electrolyte decomposition on Li metal are, however, challenging issues for the practical application of these batteries. In this connection, an electrochemically active two-dimensional phosphorene-derived lithium phosphide is introduced as a Li metal protective layer, where the nanosized protective layer on Li metal suppresses electrolyte decomposition and Li dendrite growth. This suppression is attributed to thermodynamic properties of the electrochemically active lithium phosphide protective layer. The electrolyte decomposition is suppressed on the protective layer because the redox potential of lithium phosphide layer is higher than that of electrolyte decomposition. Li plating is thermodynamically unfavorable on lithium phosphide layers, which hinders Li dendrite growth during cycling. As a result, the nanosized lithium phosphide protective layer improves the cycle performance of Li symmetric cells and Li-O2 batteries with various electrolytes including lithium bis(trifluoromethanesulfonyl)imide in N,N-dimethylacetamide. A variety of ex situ analyses and theoretical calculations support these behaviors of the phosphorene-derived lithium phosphide protective layer.

20.
PLoS One ; 12(12): e0189972, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29253022

RESUMO

Biologically uncommon d-aspartate (d-Asp) residues have been shown to accumulate in proteins associated with age-related human disorders, such as cataract and Alzheimer disease. Such d-Asp-containing proteins are unlikely to be broken down completely because metabolic enzymes recognize only proteins or peptides composed exclusively of l-amino acids. Therefore, undigested d-Asp-containing peptides may exist in blood and, if detectable, may be a useful biomarker for associated diseases. In this study, we investigated d-amino acid-containing peptides in adult human serum by a qualitative d-amino acid analysis based on a diastereomer method and LC-MS/MS method. As a result, two d-Asp-containing peptides were detected in serum, both derived from the fibrinogen ß-chain, a glycoprotein that helps in the formation of blood clots. One of the peptides was fibrinopeptide B, which prevents fibrinogen from forming polymers of fibrin, and the other was same peptide with C-terminal Arginine missing. To our knowledge, this is the first report of the presence of d-amino acid-containing peptides in serum and the approach described will provide a new direction on the serum proteome and fragmentome.


Assuntos
Aminoácidos/sangue , Peptídeos/sangue , Adulto , Doença de Alzheimer/sangue , Aminoácidos/química , Ácido Aspártico/metabolismo , Biomarcadores/sangue , Catarata/sangue , Cromatografia Líquida , Cristalinas/metabolismo , Fibrinogênio/metabolismo , Fibrinopeptídeo B/análise , Humanos , Pessoa de Meia-Idade , Proteômica , Espectrometria de Massas em Tandem , Adulto Jovem
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