Comparison of Diagnostic Performance of Three-Dimensional Positron Emission Mammography versus Whole Body Positron Emission Tomography in Breast Cancer

Objective. To compare the diagnostic performance of three-dimensional (3D) positron emission mammography (PEM) versus whole body positron emission tomography (WBPET) for breast cancer. Methods. A total of 410 women with normal breast or benign or highly suspicious malignant tumors were randomized at 1 : 1 ratio to undergo 3D-PEM followed by WBPET or WBPET followed by 3D-PEM. Lumpectomy or mastectomy was performed on eligible participants after the scanning. Results. The sensitivity and specificity of 3D-PEM were 92.8% and 54.5%, respectively. WBPET showed a sensitivity of 95.7% and specificity of 56.8%. After exclusion of the patients with lesions beyond the detecting range of the 3D-PEM instrument, 3D-PEM showed higher sensitivity than WBPET (97.0% versus 95.5%, P = 0.913), particularly for small lesions (<1 cm) (72.0% versus 60.0%, P = 0.685). Conclusions. The 3D-PEM appears more sensitive to small lesions than WBPET but may fail to detect lesions that are beyond the detecting range. This study was approved by the Ethics Committee (E2012052) at the Tianjin Medical University Cancer Institute and Hospital (Tianjin, China). The instrument positron emission mammography (PEMi) was approved by China State Food and Drug Administration under the registration number 20153331166

Structure-function analysis of CYP719As involved in methylenedioxy bridge-formation in the biosynthesis of benzylisoquinoline alkaloids and its de novo production

Benzylisoquinoline alkaloids (BIAs) are a type of secondary metabolite with clinical application value. (S)-stylopine is a special BIA which contains methylenedioxy bridge structures. CYP719As could catalyze the methylenedioxy bridge-formation on the A or D rings of protoberberine alkaloids, while displaying significant substrate regiospecificity. To explore the substrate preference of CYP719As, we cloned and identified five CyCYP719A candidates from Corydalis yanhusuo. Two CyCYP719As (CyCYP719A39 and CyCYP719A42) with high catalytic efficiency for the methylenedioxy bridge-formation on the D or A rings were characterized, respectively. The residues (Leu 294 for CyCYP719A42 and Asp 289 for CyCYP719A39) were identified as the key to controlling the regioselectivity of CYP719As affecting the methylenedioxy bridge-formation on the A or D rings by homology modeling and mutation analysis. Furthermore, for de novo production of BIAs, CyCYP719A39, CyCYP719A42, and their mutants were introduced into the (S)-scoulerine-producing yeast to produce 32\ua0mg/L (S)-stylopine. These results lay a foundation for understanding the structure-function relationship of CYP719A-mediated methylenedioxy bridge-formation and provide yeast strains for the BIAs production by\ua0synthetic biology

Catalytic promiscuity of O-methyltransferases from Corydalis yanhusuo leading to the structural diversity of benzylisoquinoline alkaloids

O-methyltransferases play essential roles in producing structural diversity and improving the biological properties of benzylisoquinoline alkaloids (BIAs) in plants. In this study, Corydalis yanhusuo, a plant used in traditional Chinese medicine due to the analgesic effects of its BIA-active compounds, was employed to analyze the catalytic characteristics of O-methyltransferases in the formation of BIA diversity. Seven genes encoding O-methyltransferases were cloned, and functionally characterized using seven potential BIA substrates. Specifically, an O-methyltransferase (CyOMT2) with highly efficient catalytic activity of both 4′- and 6-O-methylations of 1-BIAs was found. CyOMT6 was found to perform two sequential methylations at both 9- and 2-positions of the essential intermediate of tetrahydroprotoberberines, (S)-scoulerine. Two O-methyltransferases (CyOMT5 and CyOMT7) with wide substrate promiscuity were found, with the 2-position of tetrahydroprotoberberines as the preferential catalytic site for CyOMT5 (named scoulerine 2-O-methyltransferase) and the 6-position of 1-BIAs as the preferential site for CyOMT7. In addition, results of integrated phylogenetic molecular docking analysis and site-directed mutation suggested that residues at sites 172, 306, 313, and 314 in CyOMT5 are important for enzyme promiscuity related to O-methylations at the 6- and 7-positions of isoquinoline. Cys at site 253 in CyOMT2 was proved to promote the methylation activity of the 6-position and to expand substrate scopes. This work provides insight into O-methyltransferases in producing BIA diversity in C. yanhusuo and genetic elements for producing BIAs by metabolic engineering and synthetic biology

Hydrogen Sulfide Protects against Chemical Hypoxia-Induced Cytotoxicity and Inflammation in HaCaT Cells through Inhibition of ROS/NF-κB/COX-2 Pathway

Hydrogen sulfide (H2S) has been shown to protect against oxidative stress injury and inflammation in various hypoxia-induced insult models. However, it remains unknown whether H2S protects human skin keratinocytes (HaCaT cells) against chemical hypoxia-induced damage. In the current study, HaCaT cells were treated with cobalt chloride (CoCl2), a well known hypoxia mimetic agent, to establish a chemical hypoxia-induced cell injury model. Our findings showed that pretreatment of HaCaT cells with NaHS (a donor of H2S) for 30 min before exposure to CoCl2 for 24 h significantly attenuated CoCl2-induced injuries and inflammatory responses, evidenced by increases in cell viability and GSH level and decreases in ROS generation and secretions of IL-1β, IL-6 and IL-8. In addition, pretreatment with NaHS markedly reduced CoCl2-induced COX-2 overexpression and PGE2 secretion as well as intranuclear NF-κB p65 subunit accumulation (the central step of NF-κB activation). Similar to the protective effect of H2S, both NS-398 (a selective COX-2 inhibitor) and PDTC (a selective NF-κB inhibitor) depressed not only CoCl2-induced cytotoxicity, but also the secretions of IL-1β, IL-6 and IL-8. Importantly, PDTC obviously attenuated overexpression of COX-2 induced by CoCl2. Notably, NAC, a ROS scavenger, conferred a similar protective effect of H2S against CoCl2-induced insults and inflammatory responses. Taken together, the findings of the present study have demonstrated for the first time that H2S protects HaCaT cells against CoCl2-induced injuries and inflammatory responses through inhibition of ROS-activated NF-κB/COX-2 pathway

Adaptive fuzzy dynamic surface control for unknown time delay nonlinear systems preceded by unknown asymmetric hysteresis

In this paper, a fuzzy approximator based adaptive dynamic surface control scheme is proposed for a class of unknown time delay nonlinear systems preceded by asymmetric hysteresis nonlinearities. The features of the proposed method are: 1) by combining the approximated property of the fuzzy logic systems (FLSs) with the Finite Covering Lemma, the Krasovskii functionals are disposed of, achieving the L∞ norm of the tracking error by using the initializing technique; 2) the assumptions on the time-delay functions are removed due to the use of the Finite Covering Lemma and the FLSs; 3) the proposed adaptive fuzzy dynamic surface control scheme can also compensate the asymmetric shifted Prandtl Ishlinskii (ASPI) hysteresis without constructing the inverse of the ASPI model with the density function of ASPI model being unknown and estimated on-line to compensate the hysteresis. It is proved that all the signals in the closed-loop system are ultimately uniformly bounded and can be made arbitrarily small. Simulation results show the validity of the proposed method

Effect of PBAT on Property of PLA/PHB Film Used for Fruits and Vegetables

A blend of poly(lactic acid) (PLA) (70% by weight) and poly(3-hydroxybutyrate) (PHB) (30% by weight) with a solubilizing agent (PBAT) at four different concentrations (5%, 10%, 15% and 20% by weight per 100 parts of the blends) were investigated by FTIR, SEM, mechanical testing, water vapor permeability test and biodegradation studies. SEM showed that PBAT can improve the compatibility between PLA and PHB. The film show a great Oxygen transmission rate and Water vapor permeability property when the content of PBAT is 10%

Effect of PBAT on Property of PLA/PHB Film Used for Fruits and Vegetables

A blend of poly(lactic acid) (PLA) (70% by weight) and poly(3-hydroxybutyrate) (PHB) (30% by weight) with a solubilizing agent (PBAT) at four different concentrations (5%, 10%, 15% and 20% by weight per 100 parts of the blends) were investigated by FTIR, SEM, mechanical testing, water vapor permeability test and biodegradation studies. SEM showed that PBAT can improve the compatibility between PLA and PHB. The film show a great Oxygen transmission rate and Water vapor permeability property when the content of PBAT is 10%

Adaptive output-feedback inverse control for a class of time delay nonlinear hysteretic systems via fuzzy approximeter

In this paper, an fuzzy approximator based output feedback adaptive dynamic surface inverse control (DSIC) scheme is proposed for a class of time-delay systems preceded by unknown asymmetric hysteresis. The main advantages are as follows: 1) by combining the Finite Covering Lemma with fuzzy logic systems (FLSs), a novel time-delay function approx-imator is proposed with the benefits of the assumptions of the conservative upper bound functions on the time-delay functions are removed and the Krasovskii functionals are not required when deal with time delays. Also, the time delay functions extends to a more general one with states variables and time-delay variables being coupled; 2) by using the proposed initial technique, the Lnorm of the tracking error is obtained; 3) by constructing the inverse of the asymmetric hysteresis and approximating the unknown time-delay functions, both time delays and asymmetric hysteresis phenomena in the actuators are mitigated simultaneously when only the output of the system is available. It is proved that all the signals in the closed-loop systems are semi-globally ultimately uniformly bounded (SUUG). Simulation results show the validity of the proposed scheme

The Application of a Three-Dimensional Deterministic Model in the Study of Debris Flow Prediction Based on the Rainfall-Unstable Soil Coupling Mechanism

As debris flow is one of the most destructive natural disasters in many parts of the world, the assessment and management of future debris flows with proper forecasting methods are crucial for the safety of life and property. So increasing attention has been paid to the forecasting methods on debris flows. A debris flow forecasting method based on the rainfall-unstable soil coupling mechanism (R-USCM) is presented in the current study. This method is based on the debris flow formation mechanism. The density of sediment is introduced as an evaluation index to determine the susceptibility of debris flow occurrence. The forecasting method includes two phases: (1) rainfall and soil coupling and (2) runoff and unstable soil coupling. Scoops3D, a three-dimensional (3D) model for analyzing slope stability, was introduced into the debris flow forecasting method. In order to test the forecasting accuracy of this method, Jiaohe County was selected as a research area, and the serious debris flow disasters attributed to strong rainfall on 20 July 2017 were taken as the research case. By comparing the forecasting results with the debris flow distribution map for Jiaohe County, the method based on the R-USCM is feasible for forecasting debris flows at the regional scale. The application of the Scoops3D model can more reasonably analyze the slope stability than the traditional two dimensional (2D) method and improve the forecasting ability of debris flows

Dynamic Tracking of Injected Mesenchymal Stem Cells after Myocardial Infarction in Rats: A Serial 7T MRI Study

Purpose. To track the fate of micron-sized particles of iron oxide (MPIO) labeled mesenchymal stem cells (MSCs) in vivo in a rat myocardial infarction model using 7T magnetic resonance imaging (MRI) scanner. Materials and Methods. Male MSCs (2 × 106/50 μL) dual-labeled with MPIO and CM-DiI were injected into the infarct periphery 7 days after myocardial infarction (MI). The control group received cell-free media injection. The temporal stem cell location, signal intensity, and cardiac function were dynamically assessed using a 7T MRI at 24 h before transplantation (baseline), 3 days, 2 weeks, and 4 weeks after transplantation, respectively. Results. MR hypointensities caused by MPIOs were observed on T2⁎-weighted images at all time points after MSCs injection. Cine-MRI showed that MSCs moderated progressive left ventricular remodeling. Double staining for iron and CD68 revealed that most of the iron-positive cells were CD68-positive macrophages. Real-time PCR for rat SRY gene showed the number of survival MSCs considerably decreased after transplantation. MSC-treated hearts had significantly increased capillary density in peri-infarct region and lower cardiomyocytes apoptosis and fibrosis formation. Conclusions. Iron particles are not a reliable marker for in vivo tracking the long-term fate of MSCs engraftment. Despite of poor cell retention, MSCs moderate left ventricular remodeling after MI