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1.
J Agric Food Chem ; 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32614183

RESUMO

The production of acetone-butanol-ethanol by solventogenic Clostridium using lignocellulosic biomass can be a potential alternative to petroleum-based butanol. However, previous studies on non-detoxified lignocellulose hydrolysate could not provide better results when compared to those in synthetic medium. In this study, we engineered the pentose pathway of Clostridium beijerinckii NCIMB 8052, which was then subjected to adaptive laboratory evolution in the gradient mixture of synthetic medium and pretreated corn stover enzymatic hydrolysate (CSH) prepared according to the National Renewable Energy Laboratory (NREL) standard. The final resultant strain CIBTS1274A produced 20.7 g/L of total solvents in NREL CSH diluted to 6% initial total sugars, supplemented with ammonium acetate. This performance was comparable with corn-based butanol. In addition, this strain was successfully used in the scale-up operation using non-detoxified corn stover and corncob hydrolysate at Lignicell Refining Biotechnologies Ltd., which is the only commercial bio-butanol industry in the world.

2.
ACS Synth Biol ; 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32627539

RESUMO

l-Proline is an important amino acid that has various industrial applications. Industrial l-proline-producing strains are obtained by the mutagenesis of Corynebacterium glutamicum. In this study, the optimized C. glutamicum genome-editing tools were further applied in the de novo construction of a hyper-l-proline-producing strain. Overexpression of a feedback inhibition-resistant γ-glutamic kinase mutant ProBG149K, deletion of a proline dehydrogenase to block l-proline degradation, overexpression of glutamate dehydrogenase to increase glutamate synthesis flux, the mutation of 6-phosphate gluconate dehydrogenase and glucose-6-phosphate-dehydrogenase in the pentose phosphate pathway to enhance NADPH supply, the deletion of pyruvate aminotransferase to decrease the byproduct l-alanine synthesis, and weakening of α-ketoglutarate dehydrogenase to regulate the TCA cycle were combined to obtain ZQJY-9. ZQJY-9 produced 19.68 ± 0.22 g/L of l-proline in flask fermentation and was also demonstrated at the 3 L bioreactor level by fed-batch fermentation producing 120.18 g/L of l-proline at 76 h with the highest productivity of 1.581 g/L/h.

3.
ACS Synth Biol ; 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32551502

RESUMO

Controlling the copy number of gene expression cassettes is an important strategy to engineer bacterial cells into high-efficiency biocatalysts. Current strategies mostly use plasmid vectors, but multicopy plasmids are often genetically unstable, and their copy numbers cannot be precisely controlled. The integration of expression cassettes into a bacterial chromosome has advantages, but iterative integration is laborious, and it is challenging to obtain a library with varied gene doses for phenotype characterization. Here, we demonstrated that multicopy chromosomal integration using CRISPR-associated transposases (MUCICAT) can be achieved by designing a crRNA to target multicopy loci or a crRNA array to target multiple loci in the Escherichia coli genome. Within 5 days without selection pressure, E. coli strains carrying cargos with successively increasing copy numbers (up to 10) were obtained. Recombinant MUCICAT E. coli containing genomic multicopy glucose dehydrogenase expression cassettes showed 2.6-fold increased expression of this important industrial enzyme compared to E. coli harboring the conventional protein-expressing plasmid pET24a. Successful extension of MUCICAT to Tatumella citrea further demonstrated that MUCICAT may be generally applied to many bacterial species.

4.
Nanotechnology ; 2020 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-32464623

RESUMO

MoS2 films as an excellent solid lubricating film can significantly decrease the friction and adhesion of nanoelectromechanical system. Atomic layer deposition (ALD) as a surface controlled method provides a flexible way to apply MoS2 to complex surfaces. In the work, the MoS2 film deposited by ALD on the substrates with plasma-assisted process is used to study controlled friction. Firstly, layer-controlled MoS2 films were fabricated by ALD from 1 to 5 layers. The friction is decreasing as the number of layers increased. Furthermore, the average friction force of MoS2 deposited on Al2O3 substrates treated by plasma for 10 s with 1 ALD cycle has the lowest value. The functional groups on the substrate surface can be obtained by plasma treatment, which can control the growth of the first layer of MoS2 in ALD so that the friction characteristics of monolayer MoS2 can be controlled. Finally, the effect of plasma treatment on ALD growth at the intermediate stage of MoS2 is relatively weak. Only the monolayer MoS2 treated by plasma can affect the growth of MoS2 by ALD. Therefore, the controlling effect of plasma treatment on the friction characteristics of MoS2 deposited by ALD mainly occurs at the initial stage of growth.

5.
Sci Rep ; 10(1): 6876, 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32327694

RESUMO

Human microbiota play an important role in the health of their human hosts. Recent studies have demonstrated that microbiota exist in seminal plasma. The current study aims to elucidate whether seminal microbiota exist in patients with different types of dysspermatism and whether bacterial biomarkers can be identified for them. A total of 159 study participants were recruited, including 22 patients with oligoasthenospermia, 58 patients with asthenospermia, 8 patients with azoospermia, 13 patients with oligospermia, and 58 matched healthy controls. Seminal microbiota composition was analyzed using 16S rRNA gene-based sequencing. The results showed that the composition of seminal microbiota of patients with dysspermatism differed from those of healthy controls. Comparison of the microbiota composition in semen samples from patients with different types of dysspermatism showed that microbiota in patients with asthenospermia and oligoasthenospermia were distinct from healthy controls in beta diversity (P < 0.05). Characteristic biomarkers, including Ureaplasma, Bacteroides, Anaerococcus, Finegoldia, Lactobacillus and Acinetobacter lwoffii, were identified based on LEfSe analysis. Inferred functional analysis based on seminal microbiome data further indicated the presence of potential pathogenic biomarkers in patients with asthenospermia and oligoasthenospermia. These results provided profiles of seminal microbiota exhibited in different types of dysspermatism, thus providing new insights into their pathogenesis.

6.
Materials (Basel) ; 13(6)2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32245236

RESUMO

Surface hardening treatment can usually introduce severe grain distortion with a large gradient in the surface layer. It results in mechanical properties being difficult to accurately determine through macroscopic tests due to the non-uniformity of the shot-peened material. In this study, the mechanical behavior of uniformly pre-deformed nickel-based superalloy IN718 was investigated with monotonic tensile tests and instrumented indentation tests. For the shot-peened material, the hardness distribution of the surface hardening layer after shot peening was identified through the instrumented indentation method. According to the stress-strain results of pre-deformed materials, Ramberg-Osgood model parameters could be presented with plastic deformation. Assuming the power-law relationship between hardness and plastic deformation, the plastic deformation distribution along the depth of the surface hardening layer was clarified. Based on the results, a method to identify the stress-strain relationships of hardened material at different depths was established. Finally, the finite-element simulations of the instrumented indentation test considered residual stress and strain hardening were built to verify the method presented herein. The results show that the solution to evaluate the mechanical properties of hardening layer materials in the microscopic zone is feasible, which can provide the foundation for the failure analysis of shot-peened materials.

7.
Nanoscale ; 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32239028

RESUMO

Herein, ruthenium (Ru) nanoparticles were anchored on carbon nanotubes (Ru/CNTs) functionalized as catalyst cathodes for non-aqueous Li-CO2 cells. For cycling tests through a low cut-off capacity (100 mA h g-1), the origin of battery deterioration resulted from the accumulation of Li2CO3 discharging products on catalytic surfaces, identical to the observations in previous studies. However, the Li-CO2 cells in this work showed a sudden death within several cycles of high cut-off capacity (500 mA h g-1), and no Li2CO3 residues were investigated on the cathode. In contrast, Li dendrites and passivation materials (LiOH and Li2CO3) were generated on Li anodes upon cycling at a limited capacity of 500 mA h g-1, which dominantly contributed to the battery degradation. A Li foil-replacement method was adopted to make the Ru/CNT cathode perform continuous 100 cycles under a cut-off capacity of 500 mA h g-1. These results indicate that not only Li2CO3 residues blocked on the active sites of the cathode but also Li dendrites and passivation materials produced on the anode caused Li-CO2 battery deterioration. Moreover, in the present work, a carbon thin film was deposited on Li metal (C/Li) by a sputtering system for suppressing the dendrite formation upon cycling and promoting the defense of the H2O attack from the electrolyte disintegration. The Li-CO2 cell with a Ru/CNT catalyst and a C/Li anode revealed an improved electrochemical stability of 115 cycles at a limited capacity of 500 mA h g-1. This proto strategy provided a significant research direction focusing on Li anodes for elevating the Li-CO2 battery durability.

8.
Pharmacol Res ; 157: 104784, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32305492

RESUMO

The prevalence of autism spectrum disorders (ASD) is increasing, but its etiology remains elusive and hence an effective treatment is not available. Previous research conducted on animal models suggests that microbiota-gut-brain axis may contribute to ASD pathology and more human research is needed. This study was divided into two stages,.At the discovery stage, we compared the differences in gut microbiota profiles (using 16S rRNA sequencing), fecal SCFAs (using GC-MS) and plasma neurotransmitters (using UHPLC-MS/MS) of 26 children with ASD and 24 normal children. All 26 children with ASD participated in the intervention stage, and we measured the gut microbiota profiles, SCFAs and neurotransmitters before and after probiotics + FOS (n = 16) or placebo supplementation (n = 10). We found that gut microbiota was in a state of dysbiosis and significantly lower levels of Bifidobacteriales and Bifidobacterium longum were observed at the discovery stage in children with ASD. An increase in beneficial bacteria (Bifidobacteriales and B. longum) and suppression of suspected pathogenic bacteria (Clostridium) emerged after probiotics + FOS intervention, with significant reduction in the severity of autism and gastrointestinal symptoms. Compared to children in the control group, significantly lower levels of acetic acid, propionic acid and butyric acid were found, and a hyperserotonergic state (increased serotonin) and dopamine metabolism disorder (decreased homovanillic acid) were observed in children with ASD. Interestingly, the above SCFAs in children with autism significantly elevated after probiotics + FOS intervention and approached those in the control group. In addition, our data demonstrated that decreased serotonin and increased homovanillic acid emerged after probiotics + FOS intervention. However, the above-mentioned changes did not appear in the placebo group for ASD children. Probiotics + FOS intervention can modulate gut microbiota, SCFAs and serotonin in association with improved ASD symptoms, including a hyper-serotonergic state and dopamine metabolism disorder.

9.
Endocrine ; 68(3): 564-572, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32246318

RESUMO

PURPOSE: Oral microbiota maintains a dynamic ecological balance with the host. However, a disruption in this balance can lead to oral diseases such as dental caries and periodontitis. Several studies suggest differences in microbial composition in the oral cavity between patients with T2DM and nondiabetic patients. However, there is inadequate oral microbiome-related data from Chinese patients with T2DM, and the difference in microbiome profile between Chinese patients with T2DM and other ethnicities needs to be investigated further. METHOD: Oral swab samples were collected from 280 adult patients with T2DM and 162 healthy controls. Illumina sequencing was performed on oral samples targeting V1-V2 region of 16S rRNA gene and sequence analysis was carried in the QIIME. RESULTS: Patients with T2DM and healthy cohorts exhibited distinct oral microbial clusters based on principal coordinate analysis (PCoA). The Firmicutes/Bacteroidetes ratio increased in T2DM and T2DM patients presented significantly higher numbers of Neisseria, Streptococcus, Haemophilus, and Pseudomonas genera, and lower numbers of Acinetobacteria compared with healthy controls. When compared with the available published data of oral and gut microbiome associated with T2DM patients, we found the ratio of Firmicutes/Bacteroidetes and the abundance of Haemophilus could be a specific microbial biomarker in Chinese patients with T2DM. CONCLUSIONS: Our study revealed a significant difference in the oral microbiota between T2DM patients and healthy individuals. We identified 25 taxa, including 6 genera, with significant difference in abundance between T2DM and healthy controls.

10.
J Thorac Imaging ; 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32168164

RESUMO

OBJECTIVE: To evaluate the diagnostic performance of automated quantitative analysis by coronary computed tomography angiography (CCTA) in identifying lesion-specific hemodynamic abnormality. METHODS: A total of 132 patients (mean age, 61 y; 86 men) with 169 vessels (with 30% to 90% diameter stenosis), who successively underwent invasive coronary angiography with evaluation of fractional flow reserve (values ≤0.8 were defined as lesion-specific hemodynamic abnormalities), were analyzed by CCTA. CCTA images were quantitatively analyzed using automated software to obtain the following index: maximum diameter stenosis (MDS%); maximum area stenosis (MAS%); lesion length (LL); volume and burden (plaque volume×100 per vessel volume) of total plaque (total plaque volume [TPV], total plaque burden [TPB]), calcified plaque (calcified plaque volume [CPV], calcified plaque volume burden [CPB]), noncalcified plaque (noncalcified plaque volume [NCPV], noncalcified plaque volume burden [NCPB]), lipid plaque (lipid plaque volume [LPV], lipid plaque burden [LPB]), and fibrous plaque (fibrotic plaque volume [FPV], fibrotic plaque burden [FPB]); napkin-ring sign (NRS); remodeling index (RI); and eccentric index (EI). Logistic regression and area under the receiver operating characteristics (AUC) were used for statistical analysis. RESULTS: Fractional flow reserve ≤0.80 was found in 57 (33.73%) of the 169 vessels. Vessels with hemodynamic significance had greater MDS% (64.43%±8.69% vs. 57.33%±9.95%, P<0.001), MAS% (73.18%±8.56% vs. 64.66%±8.95%, P<0.001), and lipid plaque burden (12.75% [9.73%, 19.56%] vs. 9.41% [4.10%, 15.70%], P=0.01) compared with vessels with normal hemodynamics. In multivariable logistic regression analysis, MAS% >68% (odds ratio: 7.20, 95% confidence interval [CI]=2.89-17.91, P<0.001) and LPB >10.03% (odds ratio=4.32, 95% CI=1.36-13.66, P=0.01) were significant predictors of hemodynamic abnormalities. In predicting lesion-specific hemodynamic abnormalities, the AUC was 0.77 (95% CI=0.70-0.85) for MAS% versus 0.71 (95% CI=0.63-0.79) for MDS% (P<0.05), 0.66 (95% CI=0.58-0.74) for LPV (P<0.05), 0.66 (95% CI=0.58-0.74) for LPB (P<0.05), and 0.63 (95% CI=0.54-0.71) for TPB (P<0.05). The AUC of MAS%+LPB (0.83, 95% CI=0.76-0.89) was significantly improved compared with that of MAS% (0.77, 95% CI=0.70-0.85, P<0.05). CONCLUSIONS: Compared with MDS% and the volume burdens of plaque compositions, MAS% has a higher diagnostic accuracy for coronary hemodynamic abnormalities in the precise quantitative analysis of coronary plaques on the basis of CT. Furthermore, MAS%+LPB might improve the diagnostic accuracy beyond MAS% alone.

11.
Differentiation ; 113: 19-25, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32203821

RESUMO

Laterality disease is frequently associated with congenital heart disease (CHD). However, it is unclear what is behind this association, a pleiotropic effect of common genetic causes of laterality diseases or the impact of abnormal left-right patterning on the downstream cardiovascular development. MEGF8 is a disease gene of Carpenter syndrome characterized by defective lateralization and CHD. Here we performed spatial and temporal deletion to dissect the tissue and time requirements of Megf8 on cardiovascular development. None of conditional deletions in cardiomyocytes, endothelium/endocardium, epicardium, cardiac mesoderm or neural crest cells led to cardiovascular defects. More surprisingly, temporal deletion with a ubiquitous Cre driver at embryonic day 7.5 (E7.5), a time point before symmetry break and cardiogenesis, causes preaxial polydactyly (PPD) and exencephaly, but not laterality and cardiovascular defects. These data suggested that Megf8 was dispensable for cardiac organogenesis. Only with E6.5 deletion, we observed aortic arch artery defects including right aortic arch, an indicator of reversed left-right patterning. The concurrence of laterality and cardiovascular defects in pre-streak stage deletion rather than cardiac organogenesis stage deletion indicates that the laterality defect may directly impact heart development. Interestingly, the latent effect of Megf8 on the left-right patterning suggests that the regulation of laterality may be much earlier than we previously thought.

12.
Artigo em Inglês | MEDLINE | ID: mdl-32050578

RESUMO

Background: Abdominal adiposity is an important risk factor of chronic cardiovascular diseases, thus the prediction of abdominal adiposity and obesity can reduce the risks of contracting such diseases. However, the current prediction models display low accuracy and high sample size dependence. The purpose of this study is to put forward a new prediction method based on an improved support vector machine (SVM) to solve these problems. Methods: A total of 200 individuals participated in this study and were further divided into a modeling group and a test group. Their physiological parameters (height, weight, age, the four parameters of abdominal impedance and body fat mass) were measured using the body composition tester (the universal INBODY measurement device) based on BIA. Intelligent algorithms were used in the modeling group to build predictive models and the test group was used in model performance evaluation. Firstly, the optimal boundary C and parameter gamma were optimized by the particle swarm algorithm. We then developed an algorithm to classify human abdominal adiposity according to the parameter setup of the SVM algorithm and constructed the prediction model using this algorithm. Finally, we designed experiments to compare the performances of the proposed method and the other methods. Results: There are different abdominal obesity prediction models in the 1 KHz and 250 KHz frequency bands. The experimental data demonstrates that for the frequency band of 250 KHz, the proposed method can reduce the false classification rate by 10.7%, 15%, and 33% in relation to the sole SVM algorithm, the regression model, and the waistline measurement model, respectively. For the frequency band of 1 KHz, the proposed model is still more accurate. (4) Conclusions: The proposed method effectively improves the prediction accuracy and reduces the sample size dependence of the algorithm, which can provide a reference for abdominal obesity.

13.
J Nat Med ; 74(2): 441-447, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31912311

RESUMO

Three new benzylisoquinoline alkaloids, (1'S)-12'-hydroxyl-linderegatine (1), (1S)-5'-O-p-hydroxybenzoyl norreticuline (2), (1R, 1'R)-11,11'-biscoclaurine (3), along with 18 known compounds were isolated from the roots of Lindera aggregata (Sims) Kosterm. Their structures were determined on the basis of extensive spectroscopic analysis (IR, UV, HR-ESI-MS, 1D and 2D NMR). The absolute configurations of three new compounds were determined by comparing their experimental and calculated ECD for the first time. Compounds (4) and (9) showed cytotoxic activities against human colon carcinoma cell line (HCT-116), with IC50 values of 51.4 and 27.1 µM, respectively. Furthermore, compounds (10) and (11) showed inhibitory activities on nitric oxide production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells, with IC50 values of 37.8 and 38.7 µM, respectively.


Assuntos
Lindera/química , Medicina Tradicional Chinesa/métodos , Raízes de Plantas/química , Humanos , Estrutura Molecular
14.
Curr Microbiol ; 77(3): 415-424, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31894374

RESUMO

Massive blood loss, a common pathological complication in the clinic, is often accompanied by altered gut integrity and intestinal wall damage. Little is known to what extent the gut microbiome could be correlated with this process. The gut microbiome plays a crucial role in human health, especially in immune and inflammatory responses. This study aims to determine whether acute blood loss affects the gut microbiome and the dynamic variation of the gut microbiome following the loss of blood. We used New Zealand rabbits to mimic the blood loss complication and designed a five-time-point fecal sampling strategy including 24-h pre-blood loss procedure, 24 h, 36 h, 48 h, and 1-week post-blood loss procedure. Gut microbiome composition and diversity were analyzed using 16S rRNA gene sequencing and downstream α-diversity, ß-diversity, and taxonomy analysis. The gut microbiome changed dramatically after blood loss procedure. There was a significant increase in diversity and richness of the gut microbiome at 24-h post-procedure (P = 0.038). Based on an analysis of similarities, the composition of gut microbiome in the samples collected at 24-h post-procedure was significantly different from that of pre-procedure samples (r = 0.79, P = 0.004 weighted unifrac distance; r = 0.99, P = 0.002, unweighted unifrac distance). The relative abundance of Lactobacillus was significantly decreased in the post-procedure samples (P = 0.0006), while the relative abundance of Clostridiales (P = 0.018) and Bacteroidales (P = 0.015) was significantly increased after procedure. We also found the relative abundance of Bacilli, Lactobacillus, Myroides, and Prevotella decreased gradually at different time points after blood loss. The relative abundance of the Clostridia, Alphaproteobacteria, and Sporosarcina increased at 24-h post-procedure and decreased thereafter. This preliminary study discovered potential connections between blood loss and dysbiosis of gut microbiome. The diversity and abundance of the gut microbiome was affected to various extents after acute blood loss and unable to be restored to the original microbiome profile even after one week. The increase in relative abundance of opportunistic pathogens after blood loss could be an important indication to reconsider immune and inflammatory responses after acute blood loss from the perspective of gut microbiome.

15.
Environ Toxicol ; 35(2): 268-276, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31696645

RESUMO

Testicular damage is the anomaly that will often accompany diabetes mellitus. Thus, this study aimed to investigate the role that total flavonoids of Epimedium (TFE) played against streptozotocin (STZ)-induced diabetic testicular dysfunction and to elucidate the mechanism of action. The diabetic rat model was induced by vein injection of STZ in healthy rats. Thirty male healthy Spraque-Dawley rats were randomly divided into following groups: the control group, the diabetic group, and the diabetic + TFE group. Gastrointestinal administration begins at fifth week of TFE for 6 weeks. After TFE administration, all animals were euthanized. Testicular tissue samples and blood samples of rats were collected for histopathological examination and for determination of levels of various biomarkers including blood glucose, testosterone, testicular enzymes, and oxidative stress indicators. All testes were weighted to calculate the testicular organ index. Hematoxylin-eosin staining was used for observing the testis and epididymis pathological changes. Protein expression (monocyte chemoattractant protein-1, transforming growth factor-beta-1, interleukin-6, and 3-beta-hydroxysteroid dehydrogenase) was detected by immunohistochemistry and western blot techniques. There was a significant difference in the changes between the diabetes group and the control group. As a result of treat with TFE, the blood glucose decreased but there was no significant difference, and other indicators showed significant improvement. TFE may protect against STZ-induced testicular injury by suppressing inflammation and oxidative stress.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Epimedium/química , Flavonoides/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Biomarcadores/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/imunologia , Epididimo/efeitos dos fármacos , Epididimo/imunologia , Epididimo/patologia , Flavonoides/isolamento & purificação , Inflamação , Masculino , Estresse Oxidativo/imunologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Estreptozocina , Testículo/imunologia , Testículo/patologia
16.
IEEE Trans Neural Netw Learn Syst ; 31(2): 589-599, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30990449

RESUMO

Blind source separation (BSS) is a typical unsupervised learning method that extracts latent components from their observations. In the meanwhile, convolutive BSS (CBSS) is particularly challenging as the observations are the mixtures of latent components as well as their delayed versions. CBSS is usually solved in frequency domain since convolutive mixtures in time domain is just instantaneous mixtures in frequency domain, which allows to recover source frequency components independently of each frequency bin by running ordinary BSS, and then concatenate them to form the Fourier transformation of source signals. Because BSS has inherent permutation ambiguity, this category of CBSS methods suffers from a common drawback: it is very difficult to choose the frequency components belonging to a specific source as they are estimated from different frequency bins using BSS. This paper presents a tensor framework that can completely eliminate the permutation ambiguity. By combining each frequency bin with an anchor frequency bin that is chosen arbitrarily in advance, we establish a new virtual BSS model where the corresponding correlation matrices comply with a block tensor decomposition (BTD) model. The essential uniqueness of BTD and the sparse structure of coupled mixing parameters allow the estimation of the mixing matrices free of permutation ambiguity. Extensive simulation results confirmed that the proposed algorithm could achieve higher separation accuracy compared with the state-of-the-art methods.

17.
Adv Mater ; 32(5): e1902301, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31328845

RESUMO

Fiber is a symbol of human civilization, being ubiquitous but obscure in society over most of history. Fiber has been revived upon the advent of fiber-based electronic devices in the past two decades. This is due to its desirable lightweight, flexible, and conformable characteristics, which enable it to play a fundamental role in the electronic and information era. Numerous fiber-based electronic devices have sprung up in energy conversion, energy storage, sensing, actuation, etc. A possibility is thereby conceived that they can be integrated into smart systems compatible with the human body, consisting of biotic fiber-based organs and tissues, which possess similar but more advanced functions. However, the design of mono-/multifibers, the construction of fiber-based devices, and the integration of these smart systems represent great challenges in fundamental understanding and practical implementation. A systematic review of the current state of the art with respect to the design and fabrication of electronic fiber materials, construction of fiber-based devices, and integration of smart systems is presented. In addition, limitations of current fiber-based devices and perspectives are explored toward potential and promising smart integration.

18.
JACC Cardiovasc Imaging ; 13(4): 966-976, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31542524

RESUMO

OBJECTIVES: The aim of this study was to evaluate the diagnostic accuracy of stress myocardial blood flow ratio (SFR), a novel parameter derived from stress dynamic computed tomographic perfusion (CTP), for the detection of hemodynamically significant coronary stenosis. BACKGROUND: A comprehensive cardiac computed tomographic protocol combining coronary computed tomographic angiography (CTA) and CTP can provide a simultaneous assessment of both coronary artery anatomy and ischemia. METHODS: Patients with chest pain scheduled for invasive angiography were prospectively enrolled in this study. Stress dynamic CTP was performed followed by coronary CTA using a second-generation dual-source computed tomographic system. At subsequent invasive angiography, fractional flow reserve was performed to identify hemodynamically significant stenosis. For each coronary territory, SFR was defined as the ratio of hyperemic myocardial blood flow (MBF) in an artery with stenosis to hyperemic MBF in a nondiseased artery. The diagnostic accuracy of SFR to identify hemodynamically significant stenosis was determined against the reference standard of invasive fractional flow reserve ≤0.80. RESULTS: A total of 82 patients (mean age 58.5 ± 10 years) with 101 vessels with either 1- or 2-vessel disease were included. By FFR, 48 (47.5%) vessels were deemed hemodynamically significant. Hyperemic MBF and SFR were lower for vessels with hemodynamically significant lesions (95.1 ± 32.4 ml/100 ml/min vs. 142.5 ± 31.2 ml/100 ml/min and 0.66 ± 0.14 vs. 0.90 ± 0.07, respectively; p < 0.01 for both). When compared with ≥50% stenosis by CTA, the specificity for detecting ischemia by SFR increased from 43% to 91%, while the sensitivity decreased from 95% to 62%. Accordingly, the positive and negative predictive values were 85% and 73%, respectively. The combination of stenosis ≥50% by CTA and SFR resulted in an area under the curve of 0.91, which was significantly higher compared with hyperemic MBF (area under the curve = 0.79; p = 0.013). CONCLUSIONS: Calculation of SFR by dynamic CTP provides a novel and accurate method to identify flow-limiting coronary stenosis.

19.
J Med Chem ; 63(2): 569-590, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31855426

RESUMO

The prostanoid EP4 receptor is one of the key receptors associated with inflammatory mediator PGE2-elicited immunosuppression in the tumor microenvironment. Blockade of EP4 signaling to enhance immunity-mediated tumor elimination has recently emerged as a promising strategy for cancer immunotherapy. In our efforts to discover novel subtype-selective EP4 antagonists, we designed and synthesized a class of 1H-1,2,3-triazole-based ligands that display low nanomolar antagonism activity toward the human EP4 receptor and excellent subtype selectivity. The most promising compound 59 exhibits single-digit nanomolar potency in the EP4 calcium flux and cAMP-response element reporter assays and effectively suppresses the expression of multiple immunosuppression-related genes in macrophage cells. On the basis of its favorable ADMET properties, compound 59 was chosen for further in vivo biological evaluation. Oral administration of compound 59 significantly inhibited tumor growth in the mouse CT26 colon carcinoma model accompanied by enhanced infiltration of cytotoxic T lymphocytes in the tumor tissue.

20.
Am J Med ; 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31715169

RESUMO

BACKGROUND: Despite significant progress in primary prevention, the rate of myocardial infarction has not decreased in young adults. We sought to compare the risk factor profiles and outcomes between individuals who experienced a first myocardial infarction at a very young (≤40 years) and a young (age 41-50 years) age. METHODS: We evaluated all patients ≤50 years of age admitted with a Type 1 myocardial infarction to 2 large academic hospitals from 2000 to 2016. Risk factors were determined by review of electronic medical records. The primary outcomes of interest were all-cause and cardiovascular mortality. RESULTS: Among 2097 consecutive young patients with myocardial infarction, 431 (20.5%) were ≤40 years of age. When compared with their older counterparts, very young patients had similar risk profiles, with the exception of greater substance abuse (17.9% vs 9.3%, P < .001) and less hypertension (37.9% vs 50.9%, P < .001). Spontaneous coronary artery dissection was more prevalent in very young patients (3.1% vs 1.1%, P = .003). Over a median follow-up of 11.2 years, very young myocardial infarction patients had a similar risk of all-cause and cardiovascular mortality. CONCLUSIONS: Despite being, on average, 10 years younger and having a lower prevalence of hypertension, very young myocardial infarction patients had similar 1-year and long-term outcomes when compared with those aged 41 to 50 years at the time of their index infarction. Our findings suggest the need for aggressive secondary prevention measures in very young patients who experience a myocardial infarction.

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