Mitral Annulus Geometry and Dynamic Motion Changes in Patients With Aortic Regurgitation: A Three-Dimensional Transesophageal Echocardiographic Study.

OBJECTIVE: The aim of the present study was to investigate the mitral annulus (MA) geometry and dynamic motion changes in patients with aortic regurgitation (AR) before and after aortic valve replacement (AVR). Moreover, the difference in the effect of the type of prosthetic aortic valve on MA was compared. DESIGN: Prospective observational study. SETTING: Cardiac operating room at a single hospital. PARTICIPANTS: Eighty-two patients with isolated moderate-to-severe AR who underwent AVR. Forty patients with normal valves were enrolled as controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The MA geometry and dynamic motion throughout the cardiac cycle were evaluated semiautomatically by three-dimensional transesophageal echocardiography. The severity of functional mitral regurgitation was intraoperatively evaluated. All patients were divided into 2 groups depending on the type of prosthetic valve (mechanical valve and bioprosthetic valve groups). Before AVR, compared with the control group without AR, the AR group demonstrated larger MA dimensions and the MA geometry was flatter. The contraction fraction of the MA area, perimeter, and height during the whole cardiac cycle were larger in the AR group (p < 0.05 for all). After AVR, most MA geometric and dynamic parameters decreased and functional mitral regurgitation also improved. In the postoperative subset analyses, the mechanical valve group showed a larger contraction fraction of the MA area and perimeter than the bioprosthetic valve group (p < 0.05 for both). CONCLUSIONS: The MA geometry and dynamic motion changed markedly in patients with AR. These spatial and dynamic changes were restored to a certain extent after surgical correction of the aortic valve. However, the effects produced by mechanical and bioprosthetic valves on MA were different.

The role of left atrial strain in patients with functional tricuspid regurgitation before and after annuloplasty: a long-term follow-up study.

BACKGROUND: Functional tricuspid regurgitation (TR) is common among patients with left heart disease and may recur during the follow-up period after selective tricuspid valve annuloplasty (TVA). This study aims to analyse the relationship between left atrial (LA) strain and the degree of preoperative functional TR and to explore the role of LA strain in predicting TR recurrence. METHODS: This study included 63 patients with rheumatic mitral stenosis who underwent mitral valve replacement and concomitant TVA. Additionally, 20 healthy controls were enrolled. Preoperative conventional LA echocardiographic parameters and LA strain were measured. The association between LA strain and preoperative functional TR severity was analysed by Pearson correlation. Predictors of recurrent TR were determined by multivariate logistic regression analyses. RESULTS: Compared with the control group, the mitral stenosis group developed a significant impairment in terms of LA strain. The degree of preoperative functional TR exhibited moderate correlations with LA reservoir strain (r = - 0.57) and LA conduit strain (r = 0.48). During a median follow-up period of 66.4 ± 36.4 months, TR recurred in 18 patients. Preoperative LA reservoir strain and the mean transmitral gradient were predictors of postoperative TR recurrence. When the two indexes were combined to establish a prediction, the sensitivity and specificity of prediction increased. The area under the receiver operating characteristic curve of the combined indicator was higher than those of the single indicators (0.90 vs. 0.70 and 0.72). CONCLUSIONS: LA strain correlates with preoperative functional TR severity in patients with rheumatic mitral stenosis. The LA reservoir strain and preoperative mean transmitral gradient are independent predictive factors for recurrent TR after TVA.

Evaluation of the Left Ventricular Hemodynamic Status of Double-Root Translocation Patients Through Vector Flow Mapping.

The double-root translocation (DRT) procedure is considered as a new choice for surgical management of complex congenital heart disease. Our study aims to investigate the left ventricular hemodynamic status after DRT by energy loss (EL), involving 42 patients who underwent DRT as well as 42 healthy volunteers as controls. The EL of left ventricle (LV) during different periods (rapid filling-RF, atrial contraction-AC, isovolumic contraction-IVC, rapid ejection-RE) of the same cardiac cycle were obtained and analyzed. Compared to the controls, global LV and apical three chamber-EL at AC and IVC periods in DRT group were higher (p < 0.05), and EL at RE period of DRT group was moderately lower. In the correlation analysis, the global EL at the RF was correlated with E wave (r = 0.47, p = 0.03), E/e' (r = 0.50, p = 0.02), BSA (r = - 0.54, p = 0.01), and age (r = - 0.67, p < 0.001). AC and RE- global EL were significantly correlated with E/e' (r = 0.49, r = 0.59, p < 0.05). There was a strong positive correlation between E/e' and global EL at the IVC (r = 0.62, p = 0.003) and a moderate negative correlation with age (r = - 0.44, p = 0.04). The present study confirms that EL is a feasible and reproducible indicator for quantitatively evaluating LV hemodynamic status in patients who underwent DRT and reveals that DRT can lead to approximatively normal long-term hemodynamic performance of LV.

[Study on Output Frequency Stability for Optically Pumped THz Lasers].

The frequency stability of the terahertz (THz) radiation source is one of the key issues which directly affect its application regarding to THz imaging, Radar detection, Coherent communication and so on. Based on two-photon light shift effect, the physical model for the frequency shift of optically pumped THz lasers has been built up and the analytical formula for calculating the frequency shift has been derived. Taking the optically pumped methanol(CH3OH) for example, the absorption line of methanol under different pressure has been given, the influence of the bump laser frequency offset and the power of pump laser on the frequency stability of output THz laser have been analyzed quantitatively while the effect of the pressure in THz cavity on the THz laser frequency drift has also been discussed. The results show that THz laser frequency drift increases with the increasing of the bump power, whereas it decreases with the increasing of pressure in THz cavity. The maximum of THz laser frequency drift reaches under the condition that the bump laser frequency drift is equal to a quarter of the absorbed line width of the operating gas when the bump laser frequency offset locates within a certain range. In practice, in order to improve the output frequency stability of THz laser, not only the appropriate working conditions (pressure, temperature) should be chosen, but also the measure for controlling the bump laser frequency shift within a certain range should be taken.

Determination of key enzymes for threonine synthesis through in vitro metabolic pathway analysis.

BACKGROUND: The overexpression of key enzymes in a metabolic pathway is a frequently used genetic engineering strategy for strain improvement. Metabolic control analysis has been proposed to quantitatively determine key enzymes. However, the lack of quality data often makes it difficult to correctly identify key enzymes through control analysis. Here, we proposed a method combining in vitro metabolic pathway analysis and proteomics measurement to find the key enzymes in threonine synthesis pathway. RESULTS: All enzymes in the threonine synthesis pathway were purified for the reconstruction and perturbation of the in vitro pathway. Label-free proteomics technology combined with APEX (absolute protein expression measurements) data analysis method were employed to determine the absolute enzyme concentrations in the crude enzyme extract obtained from a threonine production strain during the fastest threonine production period. The flux control coefficient of each enzyme in the pathway was then calculated by measuring the flux changes after titration of the corresponding enzyme. The isoenzyme LysC catalyzing the first step in the pathway has the largest flux control coefficient, and thus its concentration change has the biggest impact on pathway flux. To verify that the key enzyme identified through in vitro pathway analysis is also the key enzyme in vivo, we overexpressed LysC in the original threonine production strain. Fermentation results showed that the threonine concentration was increased 30% and the yield was increased 20%. CONCLUSIONS: In vitro metabolic pathways simulating in vivo cells can be built based on precise measurement of enzyme concentrations through proteomics technology and used for the determination of key enzymes through metabolic control analysis. This provides a new way to find gene overexpression targets for industrial strain improvement.

Purification and functional characterization of thermostable 5-aminolevulinic acid synthases.

OBJECTIVES: As 5-aminolevulinic acid synthase (ALAS), the key enzyme for 5-aminolevulinic acid (ALA) synthesis, is unstable, we have sought to find thermostable ALASs from thermophilic organisms. RESULTS: Three ALASs from thermophiles Geobacillus thermoglucosidasius (GT-ALAS), Laceyella sacchari (LS-ALAS) and Pseudomonas alcaliphila (PA-ALAS) were purified and characterized. All enzymes were more stable than two previously studied ALASs from Rhodopseudomonas palustris and Rhodobacter sphaeroides. There was almost no activity change after 60 h at 37 °C for the three thermostable enzymes. This contrasts with the other two enzymes which lost over 90 % activities in just 1 h. Furthermore, the specific activity of LS-ALAS (7.8 U mg(-1)) was also higher than any previously studied ALASs. CONCLUSIONS: Thermostable ALASs were found in thermophilic organisms and this paves the way for developing cell free processes for enzymatic production of ALA from bulk chemicals succinate and glycine.

Visualized study on the interaction between single bubbles and curved solid surface in flotation separation process.

The present study has been devoted to bubble-curved solid surface interaction in water, which is critical to the separation of suspended particles by air flotation. For this purpose, two particular stages of the interaction (collision and attachment) have been examined visually using high-speed photography in a laboratory-scale flotation column. The effects of the surface material and surfactant concentration on these two stages have been also studied quantitatively. The considered solid materials are the cleaned glass as hydrophilic surface and Teflon as hydrophobic surface. The experimental results show that the presence of surfactant significantly affects the collision and rebound process of a gas bubble, while there is no obvious effect of the surface material on the rebound process. An increase in surfactant concentration has been observed to suppress the rebound number and maximal distance of the bubble from the surface. Moreover, the three-phase contact time of the bubble is a strong function of the surfactant concentration and surface hydrophobicity as well as of the bubble diameter. Another important finding is that the bubble attachment is only observed at the hydrophobic Teflon surface below the surfactant CMC (critical micelle concentration). Results of this study are relevant for deep understanding of the attachment mechanism and to determine the proper conditions for a selective flotation process.

Fast detection of moisture content and freshness for loquats using optical fiber spectroscopy.

Detection of the moisture content (MC) and freshness for loquats is crucial for achieving optimal taste and economic efficiency. Traditional methods for evaluating the MC and freshness of loquats have disadvantages such as destructive sampling and time-consuming. To investigate the feasibility of rapid and non-destructive detection of the MC and freshness for loquats, optical fiber spectroscopy in the range of 200-1000 nm was used in this study. The full spectra were pre-processed using standard normal variate method, and then, the effective wavelengths were selected using competitive adaptive weighting sampling (CARS) and random frog algorithms. Based on the selected effective wavelengths, prediction models for MC were developed using partial least squares regression (PLSR), multiple linear regression, extreme learning machine, and back-propagation neural network. Furthermore, freshness level discrimination models were established using simplified k nearest neighbor, support vector machine (SVM), and partial least squares discriminant analysis. Regarding the prediction models, the CARS-PLSR model performed relatively better than the other models for predicting the MC, with R 2 P and RPD values of 0.84 and 2.51, respectively. Additionally, the CARS-SVM model obtained superior discrimination performance, with 100% accuracy for both calibration and prediction sets. The results demonstrated that optical fiber spectroscopy technology is an effective tool to fast detect the MC and freshness for loquats.

Prediction and visualization map for physicochemical indices of kiwifruits by hyperspectral imaging.

Soluble solid content (SSC), firmness, and color (L*, a*, and b*) are important physicochemical indices for assessing the quality and maturity of kiwifruits. Therefore, this research aimed to realize the nondestructive detection and visualization map for the physicochemical indices of kiwifruits at different maturity stages by hyperspectral imaging coupled with the chemometrics. To further improve the detection accuracy and working efficiency of the models, competitive adaptive reweighted sampling (CARS) and successive projection algorithm were employed to choose feature wavelengths for predicting the physicochemical indices of kiwifruits. Multiple linear regression (MLR) was designed to develop simplified detection models based on feature wavelengths for determining the physicochemical indices of kiwifruits. The results showed that 32, 18, 26, 29, and 32 feature wavelengths were extracted from 256 full wavelengths to predict the SSC, firmness, L*, a*, and b*, respectively, with the CARS algorithm. Not only was the working efficiency of the CARS-MLR model improved, but the prediction accuracy of the CARS-MLR model for determining the physicochemical indices was also at its relative best. The residual predictive deviations of the CARS-MLR model for determining the SSC, firmness, L*, a*, and b* were 3.09, 2.90, 2.32, 2.74, and 2.91, respectively, which were all above 2.3. Compared with the model based on the full spectra, the CARS-MLR model could be used to predict the physicochemical indices of kiwifruits. Finally, the visualization map for the physicochemical indices of kiwifruits at different maturity stages was generated by calculating the spectral response of each pixel on the kiwifruit samples with the CARS-MLR model. This made the detection for the physicochemical indices of kiwifruits more intuitive. This study demonstrates that hyperspectral imaging coupled with the chemometrics is promising for the nondestructive detection and visualization map for the physicochemical indices of kiwifruits, and also provides a novel theoretical basis for the nondestructive detection of kiwifruit quality.

Immobilization and Catalytic Conversion of Polysulfide by In-Situ Generated Nickel in Hollow Carbon Fibers for High-Rate Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries are considered promising energy-storage systems because of their high theoretical energy density, low cost, and eco-friendliness. However, problems such as the shuttle effect can result in the loss of active materials, poor cyclability, and rapid capacity degradation. The utilization of a structural configuration that enhances electrochemical performance via dual adsorption-catalysis strategies can overcome the limitations of Li-S batteries. In this study, an integrated interlayer structure, in which hollow carbon fibers (HCFs) were modified with in-situ-generated Ni nanoparticles, was prepared by scalable one-step carbonization. Highly hierarchically porous HCFs act as the carbon skeleton and provide a continuous three-dimensional conductive network that enhances ion/electron diffusion. Ni nanoparticles with superior anchoring and catalytic abilities can prevent the shuttle effect and increase the conversion rate, thereby promoting the electrochemical performance. This synergistic effect resulted in a high capacity retention of 582 mAh g-1 at 1 C after 100 cycles, providing an excellent rate capability of up to 3 C. The novel structure, wherein Ni nanoparticles are embedded in cotton-tissue-derived HCFs, provides a new avenue for enhancing electrochemical performance at high C rates. This results in a low-cost, sustainable, and high-performance hybrid material for the development of practical Li-S batteries.

Morphology of hypertrophied basal septum contributes to left ventricular outflow tract obstruction in patients with hypertrophic cardiomyopathy: a retrospective case-control study.

Background: Detailed assessment of basal septal morphology is essential for understanding the morphological mechanism of left ventricular outflow tract (LVOT) obstruction. We aimed to analyze the morphological alterations of the basal septum (BS) and its surrounding structures and explore their role in LVOT obstruction (LVOTO) in patients with hypertrophic cardiomyopathy (HCM). Methods: During January 2019 and December 2019, 239 patients were diagnosed with HCM at Fuwai Hospital. We retrospectively reviewed echocardiographic data sets from 105 consecutive patients with HCM [64 with hypertrophic obstructive cardiomyopathy (HOCM) and 41 with hypertrophic non-obstructive cardiomyopathy (HNOCM)] and 28 healthy controls. For quantitatively assessing the basal septal morphology, a novel measurement method was used to obtain the IVSa (the area of the BS protruding into the LVOT), LA (the largest distance of the BS protruding into the LVOT), LB (IVSa length in the direction perpendicular to the LA), and S-IVSa (IVSa divided by LB). Echocardiographic parameters associated with LVOTO were analyzed using multivariable logistic regression analyses. Results: There was no significant difference in the maximal basal septal thickness between the HOCM and HNOCM patients (P>0.99). Among the three groups, there were significant differences in the length of the anterior and posterior mitral leaflets (AML and PML), the angle between the mitral valve orifice and ascending aorta (MV-AO) angle, IVSa, LA, LB, and S-IVSa (all P<0.001). Compared with HNOCM patients, HOCM patients had significantly longer AML and PML, as well as larger MV-AO angle, IVSa, LA, and S-IVSa (P<0.001, P<0.001, P<0.001, P=0.002, P<0.001, and P=0.03, respectively). In the multivariate analysis, AML, MV-AO angle, IVSa, and S-IVSa were associated with LVOTO {odds ratio (OR) [95% confidence interval (CI)]: 0.649 (0.462-0.911), P=0.01; 0.842 (0.768-0.923), P<0.001; 1.025 (1.001-1.049), P=0.04; and 0.276 (0.101-0.754), P=0.01, respectively}. Conclusions: Morphological alterations of the BS relative to the LVOT may provide additional value for estimating the extent of LVOTO. The length of AML, MV-AO angle, IVSa, and S-IVSa were associated with LVOTO.

Nondestructive quality assessment and maturity classification of loquats based on hyperspectral imaging.

The traditional method for assessing the quality and maturity of loquats has disadvantages such as destructive sampling and being time-consuming. In this study, hyperspectral imaging technology was used to nondestructively predict and visualise the colour, firmness, and soluble solids content (SSC) of loquats and discriminate maturity. On comparison of the performance of different feature variables selection methods and the calibration models, the results indicated that the multiple linear regression (MLR) models combined with the competitive adaptive reweighting algorithm (CARS) yielded the best prediction performance for loquat quality. Particularly, CARS-MLR models with optimal prediction performance were obtained for the colour (R2P = 0.96, RMSEP = 0.45, RPD = 5.38), firmness (R2P = 0.87, RMSEP = 0.23, RPD = 2.81), and SSC (R2P = 0.84, RMSEP = 0.51, RPD = 2.54). Subsequently, distribution maps of the colour, firmness, and SSC of loquats were obtained based on the optimal CARS-MLR models combined with pseudo-colour technology. Finally, on comparison of different classification models for loquat maturity, the partial least square discrimination analysis model demonstrated the best performance, with classification accuracies of 98.19% and 97.99% for calibration and prediction sets, respectively. This study demonstrated that the hyperspectral imaging technique is promising for loquat quality assessment and maturity classification.

Accuracy of aortic annulus measurements by three-dimensional transesophageal echocardiography and predictive value for thoracic aorta aneurysm in patients with aortic regurgitation.

Background: Accurate assessment of the aortic annulus (AA) dimension and judgment of thoracic aorta aneurysm is crucial for patients with aortic regurgitation (AR) before surgery. The aim of this study was to evaluate the accuracy and reproducibility of three-dimensional transesophageal echocardiography (3D-TEE) methods for AA measurement and explore the predictive value of the AA dimensions obtained by 3D-TEE for high-risk thoracic aorta aneurysms using the gold standard of multi-slice computed tomography (MSCT). Methods: 3D-TEE was performed on 111 patients with pure moderate-to-severe AR, and MSCT examination was conducted simultaneously. AA dimensions were obtained using reconstruction software for these two imaging techniques. Thoracic aortic diameters at standard anatomic landmarks were also measured by MSCT. All patients were divided into two groups depending on the presence of high-risk thoracic aorta aneurysms. Results: Compared to MSCT, 3D-TEE overestimated all AA parameters. However, no statistically significant differences were found in the average bias between methods (minimum diameter: 26.07±3.57 vs. 25.88±3.68 mm, P=0.52; maximum diameter: 32.30±2.68 vs. 31.78±4.06 mm, P=0.11; area: 669.76±155.19 vs. 660.05±168.28 mm2, P=0.44; perimeter: 93.52±10.42 vs. 92.26±11.71 mm, P=0.12). 3D-TEE demonstrated good correlations with MSCT measurement for AA minimum diameter, maximum diameter, area, and perimeter (r=0.63, 0.64, 0.74, 0.69, P<0.05 for all). According to the multivariate logistic regression analysis, the AA minimum diameter obtained by 3D-TEE was the best predictor for the presence of high-risk thoracic aorta aneurysms. The sensitivity and specificity for prediction were 84.6% and 63.9%, respectively, for an AA minimum diameter ≥25.74 mm (AUC: 0.759, 95% CI: 0.668-0.850). Conclusions: AA measurements obtained by the 3D-TEE method are feasible and reliable for patients with pure AR. The AA minimum diameter measured by 3D-TEE can effectively predict the presence of high-risk thoracic aorta aneurysms.

The Role of the Submitral Apparatus in Hypertrophic Obstructive Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease, is characterized by unexplained hypertrophy of any myocardial segment, and has a prevalence of 0.2% to 0.5% among the general population. As one of the phenotypes of hypertrophic cardiomyopathy, left ventricular outflow tract obstruction (LVOTO) is associated with high morbidity and mortality, including cardiac death. The integration of various factors, including septal hypertrophy, malformation of the mitral valve apparatus, and an anomalous mitral subvalvular apparatus, may contribute to the occurrence of LVOTO. Previous studies have thoroughly discussed the role of the mitral valve in the mechanisms of systolic anterior motion and LVOTO. Recent studies have shown the importance of determining the potential mechanism of the submitral apparatus in inducing systolic anterior motion and LVOTO. The authors review recent advances in knowledge regarding the submitral apparatus of patients with hypertrophic cardiomyopathy.

Biocatalytic Synthesis of Antiviral Nucleosides, Cyclic Dinucleotides, and Oligonucleotide Therapies.

Nucleosides, nucleotides, and oligonucleotides modulate diverse cellular processes ranging from protein production to cell signaling. It is therefore unsurprising that synthetic analogues of nucleosides and their derivatives have emerged as a versatile class of drug molecules for the treatment of a wide range of disease areas. Despite their great therapeutic potential, the dense arrangements of functional groups and stereogenic centers present in nucleic acid analogues pose a considerable synthetic challenge, especially in the context of large-scale manufacturing. Commonly employed synthetic methods rely on extensive protecting group manipulations, which compromise step-economy and result in high process mass intensities. Biocatalytic approaches have the potential to address these limitations, enabling the development of more streamlined, selective, and sustainable synthetic routes. Here we review recent achievements in the biocatalytic manufacturing of nucleosides and cyclic dinucleotides along with progress in developing enzymatic strategies to produce oligonucleotide therapies. We also highlight opportunities for innovations that are needed to facilitate widespread adoption of these biocatalytic methods across the pharmaceutical industry.

[Decreasing toxicity and synergistic effects of intracellular and extracellular polysaccharides from Phellinus igniarius to tumor-bearing mice].

To study the toxicity-decreasing and synergistic effect of intracellular and extracellular polysaccharides from Phellinus igniarius on S180 mice. The PIP and PIE were extracted from the products of liquid submerged fermentation of P. igniarius. Transplanting S180 mice tumor models were established so as to observe the changes in tumor inhibiting rate, indexes of the spleen and thymus, body weight, peripheral blood cells and IFN-gamma levels when CTX was used alone and when used in combination with the PIP and PIE from P. igniarius. The results indicate that the PIP and PIE from P. igniarius can increase the activity of body immunity, attenuate the toxicity of CTX as well, and improve the anti-tumor effects.

Removal of manually induced artifacts in ultrasound images of thyroid nodules based on edge-connection and Criminisi image restoration algorithm.

BACKGROUND AND OBJECTIVE: There are various artificial markers in ultrasound images of thyroid nodules, which have impact on subsequent processing and computer-aided diagnosis. The purpose of this study was to develop an approach to automatically remove artifacts and restore ultrasound images of thyroid nodules. METHODS: Fifty ultrasound images with manually induced artifacts were selected from publicly available and self-collected datasets. A combined approach was developed which consisted of two steps, artifacts detection and removal of the detected artifacts. Specifically, a novel edge-connection algorithm was used for artifact detection, detection accuracy and false discovery rate were used to evaluate the performance of artifact detection approaches. Criminisi algorithm was used for image restoration with peak signal-to-noise ratio (PSNR) and mean gradient difference to evaluate its performance. In addition, computation complexity was evaluated by execution time of relevant algorithms. RESULTS: Results revealed that the proposed joint approach with edge-connection and Criminisi algorithm could achieve automatic artifacts removal. Mean detection accuracy and mean false discovery rate of the proposed edge-connection algorithm for the 50 ultrasound images were 0.86 and 1.50. Mean PSNR of the 50 restored images by Criminisi algorithm was 36.64 dB, and mean gradient difference of the restored images was -0.002 compared with the original images. CONCLUSIONS: The proposed combined approach had a good detection accuracy for different types of manually induced artifacts, and could significantly improve PSNR of the ultrasound images. The proposed combined approach may have potential use for the repair of ultrasound images with artifacts.

Quantification of chronic aortic regurgitation using left and right ventricular stroke volumes obtained from two new automated three-dimensional transthoracic echocardiographic software: feasibility and accuracy.

The present study aimed to evaluate the feasibility and accuracy of chronic aortic regurgitation (CAR) quantification using left and right ventricular stroke volumes (LVSV and RVSV, respectively) obtained from two new automated three-dimensional transthoracic echocardiographic software-Dynamic HeartModel (DHM) and 3D Auto RV. Patients (n=116) with more than mild isolated CAR were included and divided into two groups: central (n=53) and eccentric CAR (n=63) groups. LVSV and RVSV were automatically measured by DHM and 3D Auto RV. Next, aortic regurgitant volume (ARVol) was calculated three ways: as the difference between LVSV and RVSV, by the two-dimensional proximal isovelocity surface area (PISA) method, and using effective regurgitant orifice area derived from real-time three-dimensional echocardiography (RT3DE) multiplied by CAR velocity time integral (the reference standard). DHM plus 3D Auto RV correlated well with RT3DE in ARVol measurement in both groups (central, r = 0.90; eccentric, r = 0.96), with no significant difference based on consistency analysis. In the eccentric group, PISA led to an obvious underestimation (mean difference= - 4.20 ml, P < 0.05). The kappa agreement between DHM plus 3D Auto RV and RT3DE in grading CAR severity in both groups was good (central, k = 0.89; eccentric, k = 0.86), but that between PISA and RT3DE in the eccentric CAR group was suboptimal (k = 0.74). This study indicates that ARVol quantification using DHM plus 3D Auto RV is feasible and reproducible in patients with more than mild isolated CAR. This new method has great correlation and agreement with RT3DE in ARVol measurement, with evident advantages over PISA in eccentric CAR.

Computational Redesign of an ω-Transaminase from Pseudomonas jessenii for Asymmetric Synthesis of Enantiopure Bulky Amines.

ω-Transaminases (ω-TA) are attractive biocatalysts for the production of chiral amines from prochiral ketones via asymmetric synthesis. However, the substrate scope of ω-TAs is usually limited due to steric hindrance at the active site pockets. We explored a protein engineering strategy using computational design to expand the substrate scope of an (S)-selective ω-TA from Pseudomonas jessenii (PjTA-R6) toward the production of bulky amines. PjTA-R6 is attractive for use in applied biocatalysis due to its thermostability, tolerance to organic solvents, and acceptance of high concentrations of isopropylamine as amino donor. PjTA-R6 showed no detectable activity for the synthesis of six bicyclic or bulky amines targeted in this study. Six small libraries composed of 7-18 variants each were separately designed via computational methods and tested in the laboratory for ketone to amine conversion. In each library, the vast majority of the variants displayed the desired activity, and of the 40 different designs, 38 produced the target amine in good yield with >99% enantiomeric excess. This shows that the substrate scope and enantioselectivity of PjTA mutants could be predicted in silico with high accuracy. The single mutant W58G showed the best performance in the synthesis of five structurally similar bulky amines containing the indan and tetralin moieties. The best variant for the other bulky amine, 1-phenylbutylamine, was the triple mutant W58M + F86L + R417L, indicating that Trp58 is a key residue in the large binding pocket for PjTA-R6 redesign. Crystal structures of the two best variants confirmed the computationally predicted structures. The results show that computational design can be an efficient approach to rapidly expand the substrate scope of ω-TAs to produce enantiopure bulky amines.

Poly[(µ(2)-3,6-di-4-pyridyl-1,2,4,5-tetra-zine)(µ(2)-thio-cyanato)copper(I)].

The title compound, [Cu(NCS)(C(12)H(8)N(6))](n), is a self-assembled two-dimensional metal-organic network. The Cu atom is linked by two N atoms from two 3,6-di-4-pyridyl-1,2,4,5-tetra-zine ligands and by the N and S atoms from two thio-cyanate ligands in a distorted tetra-hedral environment. The Cu atom and the thio-cyanate ligand occupy a crystallographic mirror plane m, and a crystallographic inversion centre is in the middle of the tetra-zine ring, generating the zigzag fashion of the two-dimensional network. The infinite -Cu-SCN-Cu-SCN- chain is due to translational symmetry along the a axis. These chains are further connected through the 3,6-di-4-pyridyl-1,2,4,5-tetra-zine ligands that bridge the Cu(I) centers, generating a two-dimensional network. There are π-π stacking inter-actions between the pyridine and tetra-zine rings (perpendicular distances of 3.357 and 3.418 Å), with a centroid-centroid distance of 3.6785 (16) Å.