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To improve performance in terms of overshoot and motor response speed when a permanent-magnet synchronous motor (PMSM) with a proportional–integral (PI) controller is subjected to external disturbances, this paper proposes a speed control strategy based on an enhanced Beetle Antennae Search algorithm, which allows for adjustable parameters of the PI controller within a certain range. Firstly, to enhance the global and local search capabilities of each individual beetle, the step size was improved by linearly decreasing it. Secondly, a simulation model of a PMSM closed-loop control system was built to verify the effectiveness of the improved Beetle Antennae Search (BAS) algorithm. Finally, a linear feedback shift register model that generates four random numbers was developed on a field-programmable gate array (FPGA). The improved BAS algorithm for the PMSM control system was implemented on an FPGA using the Verilog hardware description language, and the feasibility of the system was verified through hardware simulation. Additionally, the hardware resource consumption on different FPGA platforms was analyzed. The simulation results demonstrate that the proposed new speed control strategy can reduce the overshoot and improve the motor response speed. [ABSTRACT FROM AUTHOR]

Corynebacterium glutamicum porphobilinogen synthase (PBGS) is a metal enzyme with a hybrid active site metal binding sequence. In this study, the porphobilinogen synthase gene of C. glutamicum was cloned and heterogeneously expressed in Escherichia coli. C. glutamicum PBGS was purified, and its enzymatic characteristics were analyzed. The results showed that C. glutamicum PBGS is a Zn2+-dependent enzyme, and Mg2+ has allosteric regulation. The allosteric Mg2+ plays a vital role in forming the quaternary structure of C. glutamicum PBGS. Based on the ab initio predictive structure modeling of the enzyme and the molecular docking model of 5-aminolevulinic acid (5-ALA), 11 sites were selected for site-directed mutagenesis. When the hybrid active site metal binding site of C. glutamicum PBGS is converted into a cysteine-rich motif (Zn2+-dependent) or an aspartic acid-rich motif (Mg2+/K+-dependent), the enzyme activity is basically lost. Four residues, D128, C130, D132, and C140, in the metal binding site, were the binding sites of Zn2+ and the active center of the enzyme. The band migration, from the native PAGE, of five variants with mutations in the center of enzyme activity was the same as that of the variant enzymes as purified, individually adding two metal ion chelating agents. Their Zn2+ active center structures were abnormal, and the quaternary structure equilibrium was altered. The destroyed active center affects the construction of its quaternary structure. The quaternary structural balance between octamer and hexamer through dimers was regulated by the allosteric regulation of C. glutamicum PBGS. The enzyme activity was also affected by the change of the active site lid structure and (α β)8-barrel structure caused by mutation. Structural changes in the variants were analyzed to understand C. glutamicum PBGS better. [ABSTRACT FROM AUTHOR]

Background: Ovarian tissue cryopreservation and transplantation are novel therapeutic approaches for fertility preservation. However, follicle loss caused by ischemic and hypoxic damage is one of the issues after frozen-thawed ovarian tissue transplantation. Promoting angiogenesis in grafts is the key to restore cryopreserved ovarian function. Mesenchymal stem cells (MSCs) have been reported to facilitate angiogenesis in the cryopreserved ovarian tissue transplantation. However, the risk of embolization, immunogenic effect and tumorigenesis hinders the clinical application of MSCs to human organ transplantation. In this study, we established an in vitro ovarian culture system to restore frozen-thawed ovarian function before transplantation with the application of umbilical cord mesenchymal stem cells (UC-MSCs), and explored the effects of UC-MSCs on frozen-thawed ovaries in vitro ovarian culture system and the mechanisms of UC-MSCs on the angiogenesis of frozen-thawed ovaries. Methods: A simple in vitro three dimensional (3D) ovarian culture system using Matrigel was established to support to an ideal niche, and ovary was alone cultured in the 24-well plate as a control. We also evaluated the effects of UC-MSCs treatment on ovarian function with or without Matrigel support. All thawed ovaries were randomly divided into control group (Matrigel−/UC-MSCs−), Matrigel group (Matrigel+/UC-MSCs−), UC-MSCs group (Matrigel−/UC-MSCs+) and UC-MSCs + Matrigel group (Matrigel+/UC-MSCs+). HE staining was used to detect the histological structure of follicles and TUNEL staining was used to detect cell apoptosis. The number of microvessels was counted to evaluate neovascularization. The mRNA expression of VEGFA, IGF1 and ANGPT2 were detected by RT-PCR. Western blotting was used to measure the expression of GSK-3β, β-catenin and p-β-catenin. Results: In the absence of UC-MSCs, 3D culture system supported by Matrigel showed significantly improved follicular development and microvascular number. Additionally, UC-MSCs were also found to effectively improve follicular development and microvascular number regardless of the culture condition used. However, alleviated follicular apoptosis, increased mRNA expression of angiogenesis-related gene and activated Wnt/β-catenin pathway occurred only in the UC-MSCs + Matrigel group. Besides, with the application of IWP-2 in UC-MSCs + Matrigel group, Wnt//β-catenin pathway could be blocked by IWP-2 serving as one of Wnt/β-catenin pathway inhibitors. Conclusions: This in vitro study showed the beneficial effects of UC-MSCs on thawed ovaries and explored a potential mechanism inducing angiogenesis. In particular, 3D ovarian culture system supported by Matrigel further improved UC-MSCs treatment. The in vitro culture system using Matrigel and UC-MSCs may provide a potential treatment strategy for improving the success rate of thawed ovaries transplantation. [ABSTRACT FROM AUTHOR]

This article investigates the event‐triggered sliding mode control problem for uncertain networked switched systems with the external nonlinear disturbance. First, to reduce the utilization of the network bandwidth, a novel mode‐dependent continuous‐time event‐triggering scheme (ETS) including the state triggering error is proposed. A switching‐dependent auxiliary function called the triggering sliding mode function is constructed, which prevents the controller from using the extra information (the continuous state). Then, a novel switching‐dependent integral‐type switching function that depends on the states of the switching instants and includes an exponential term is proposed. Obtaining the boundary of the sliding mode region benefits from the exponential term for continuous‐time systems. Then, an event‐triggered sliding mode controller is designed, which makes the networked switched systems practical stability, and attains the sliding region around the specified sliding surface. When the constant threshold of the triggering scheme is zero, the system state can converge to zero as time goes to infinity. Moreover, it is proved that the Zeno behavior can be avoided under the proposed continuous‐time ETS. Finally, the effectiveness of the proposed method is shown by a switched Chua's circuit system. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the impacts of different drying technologies including microwave drying (MD), vacuum microwave drying (VMD), sun drying (SD), vacuum drying (VD), hot air drying (HAD), and vacuum freeze drying (VFD) on the physical characteristics, nutritional properties and antioxidant capacities of kiwifruit pomace in order to realize by-product utilization and improve energy efficiency. Results showed that both MD and VMD significantly reduced drying time by >94.6%, compared to traditional thermal drying which took 14–48 h. MD exhibited the highest content of soluble dietary fiber (9.5%) and the lowest energy consumption. Furthermore, VMD resulted in the highest content of vitamin C (198.78 mg/100 g) and reducing sugar (73.78%), and the antioxidant capacities ranked only second to VFD. Given the financial advantages and product quality, VMD was suggested to be advantageous technology in actual industrial production. [Display omitted] • Quality of kiwifruit pomace was influenced by different drying technologies. • Vacuum microwave drying (VMD) dramatically reduced drying time of kiwifruit pomace. • Microwave drying (MD) exhibited low energy consumption for kiwifruit pomace drying. • MD possessed high content of soluble dietary fiber in kiwifruit pomace. • VMD maintained high antioxidant capacities compared to conventional thermal drying. [ABSTRACT FROM AUTHOR]

Osmotic stress in the yeast limits productivity in industrial beer production under very high gravity brewing. This study focused on assessing the protective impacts of eleven plant-derived antioxidant dipeptides (PADs) on the osmotic stress tolerance of lager yeast. The results showed that PADs provided yeast with stress tolerance under osmotic stress. PADs supplementation enhanced cell membrane integrity and reduced oxidative damage. PADs upregulated the expression of SOD2 , PEX11 and CTT1 genes under osmotic stress. Moreover, the volatile compounds contents and antioxidant activities of beers were improved by PADs, suggesting favorable quality characteristics. Especially, Phe-Cys and Leu-His could increase the DPPH radical scavenging activity of beer by 41.92% and 18.78% respectively, compared with control. Therefore, PADs are industrially scalable enhancers to improve the ability of yeast to resist osmotic stress and beer quality during very high gravity brewing. [Display omitted] • PADs enhanced the osmotic stress tolerance of lager yeast. • PADs improved yeast cell membrane integrity and reduced oxidative damage. • PADs supplementation improved beer quality during very high gravity brewing. [ABSTRACT FROM AUTHOR]

Dissection of gene function requires sophisticated tools to monitor gene expression. Gene tagging with epitope peptides and fluorescent protein tags is a routine method to investigate protein expression using tag-specific antibodies and western blotting with tedious blotting and immunodetection steps. Nanoluciferase (NanoLuc) exhibits extremely bright bioluminescence and is engineered as a sensitive genetic reporter. Due to its small size and high bioluminescent activity, NanoLuc could be engineered to function as a novel protein tag that permits direct detection of tagged protein in the gel matrix (in-gel detection). In this study, we developed Gateway compatible vectors to tag proteins with NanoLuc in plants. We also tailored the in-gel detection conditions which can detect NanoLuc-tagged MPK3 from as low as 200 pg of total protein extracts. Compared to FLAG tag and western blotting-based detection, NanoLuc tag and optimized in-gel detection exhibit increased detection sensitivity but omit the blotting and immunodetection steps. We also demonstrated versatile applications of the NanoLuc-based in-gel detection method for protein expression analysis, probing protein-protein interactions by coimmunoprecipitation, and in vivo protein phosphorylation detection with Phos-tag gel electrophoresis. Finally, NanoLuc was used to tag the gene at its endogenous locus using the wheat dwarf virus replicon and CRISPR/Cas9-mediated gene targeting. Our data suggest that NanoLuc tag and in-gel detection permit fast detection of tagged protein with high sensitivity. The versatile NanoLuc toolkit and convenient in-gel detection method are expected to facilitate in vitro and in vivo protein analysis for plant functional genomics. [ABSTRACT FROM AUTHOR]

Although high gravity brewing technology has been widely used for beer industries due to its economic benefits, yeast cells are subjected to multiple environmental stresses throughout the fermentation process. Eleven bioactive dipeptides (LH, HH, AY, LY, IY, AH, PW, TY, HL, VY, FC) were selected to evaluate their effects on cell proliferation, cell membrane defense system, antioxidant defense system and intracellular protective agents of lager yeast against ethanol-oxidation cross-stress. Results showed that the multiple stresses tolerance and fermentation performance of lager yeast were enhanced by bioactive dipeptides. Cell membrane integrity was improved by bioactive dipeptides through altering the structure of macromolecular compounds of the cell membrane. Intracellular reactive oxygen species (ROS) accumulation was significantly decreased by bioactive dipeptides, especially for FC, decreasing by 33.1%, compared with the control. The decrease of ROS was closely related to the increase of mitochondrial membrane potential, intracellular antioxidant enzyme activities including superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD), and glycerol level. In addition, bioactive dipeptides could regulate the expression of key genes (GPD1 , OLE1 , SOD2 , PEX11 , CTT1 , HSP12) to enhance the multilevel defense systems under ethanol-oxidation cross-stress. Therefore, bioactive dipeptides should be potentially efficient and feasible bioactive ingredients to improve the multiple stresses tolerance of lager yeast during high gravity fermentation. [Display omitted] • Bioactive dipeptides enhanced tolerance of yeast to ethanol-oxidation cross-stress. • Bioactive dipeptides improved yeast cell membrane integrity. • Bioactive dipeptides enhanced the antioxidant defense system of yeast. • Bioactive dipeptides promoted the accumulation of intracellular glycerol in yeast. [ABSTRACT FROM AUTHOR]

Objective The cortico–thalamo–cortical network plays a key role in childhood absence epilepsy (CAE). However, the exact interaction between the cortex and the thalamus remains incompletely understood. This study aimed to investigate the dynamic changes of frequency-dependent neural networks during the initialization of absence seizures. Methods Magnetoencephalography data from 14 patients with CAE were recorded during and between seizures at a sampling rate of 6000 Hz and analyzed in seven frequency bands. Neuromagnetic sources were volumetrically scanned with accumulated source imaging. Effective connectivity networks of the entire brain, including the cortico–thalamo–cortical network, were evaluated at the source level through Granger causality analysis. Results The low-frequency (1–80 Hz) activities showed significant frontal cortical and parieto–occipito–temporal junction source localization around seizures. The high-frequency (80–250 Hz) oscillations showed predominant activities consistently localized in deep brain areas and medial frontal cortex. The increased cortico–thalamic effective connectivity was observed around seizures in both low- and high-frequency ranges. The direction was predominantly from the cortex to the thalamus at the early time, although the cortex that drove connectivity varied among subjects. Conclusions The cerebral cortex plays a key role in driving the cortico–thalamic connections at the early portion of the initialization of absence seizures. The oscillatory activities in the thalamus could be triggered by networks from various regions in the cortex. Significance The dynamic changes of neural network provide evidences that absence seizures are probably resulted from cortical initialized cortico–thalamic network. [ABSTRACT FROM AUTHOR]

Two-dimensional (2D) TiO nanosheets with high crystallinity and good light scattering properties were synthesized via a simple solvothermal process using reduced graphite oxide as a sacrificing template. X-ray diffraction patterns and electron microscopy images indicated that the prepared 2D TiO nanosheets were composed of high-crystalline anatase TiO nanoparticles. Then, the 2D anatase TiO nanosheets were used as a scattering layer of the photoelectrode, which is expected to produce high-efficiency dye-sensitized solar cells (DSSCs). Compared with ones with pure TiO nanoparticle photoelectrodes, DSSCs based on 2D TiO nanosheets as middle scattering layer yield the highest photoelectrical conversion efficiency of 7.54 %. This is because the obtained 2D TiO nanosheets have excellent light scattering, allowing for fast interfacial charge transfer, the least series resistance, and the best charge collection efficiency. These have been systematically evidenced by the electrochemical impedance spectra, intensity-modulated photocurrent spectroscopy and intensity-modulated photovoltage spectroscopy. [ABSTRACT FROM AUTHOR]

This paper addresses the state-tracking model reference adaptive control problem for a class of switched systems with parametric uncertainties, where switchings between subsystems and designed adaptive controller are asynchronous. First, we establish a stability criterion for a switched reference model and convert the state-tracking problem into the stability problem of an error switched system. Then, an adaptive law is designed, and the global practical stability of the error switched system is guaranteed under a class of switching signals characterized by a dwell-time condition. An electrohydraulic system is given as an example to demonstrate the feasibility and effectiveness of the proposed design method. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This paper investigates theH∞state tracking model reference adaptive control (MRAC) problem for a class of switched systems using an average dwell-time method. First, a stability criterion is established for a switched reference model. Then, an adaptive controller is designed and the state tracking control problem is converted into the stability analysis. The global practical stability of the error switched system can be guaranteed under a class of switching signals characterised by an average dwell time. Consequently, sufficient conditions for the solvability of theH∞state tracking MRAC problem are derived. An example of highly manoeuvrable aircraft technology vehicle is given to demonstrate the feasibility and effectiveness of the proposed design method. [ABSTRACT FROM PUBLISHER]

SUMMARY This paper investigates the state tracking problem for a class of model reference adaptive control systems with intermittent failures of all actuators. We consider the case that all actuators may suffer failures simultaneously. The concepts of failure frequency and unavailability rate are introduced to describe the failures. Because of the actuator failures, the error system is modeled as a switched system. Then, the notion of global practical stability of switched systems is presented, and sufficient conditions are provided to guarantee the global practical stability of the error system. An example of HiMAT vehicle and the simulation results demonstrate the feasibility and effectiveness of the proposed design method. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background and Aim: Circulating microRNAs (miRNAs) are potential biomarkers for cancer detection; however, little is known about their prognostic impact on oesophageal squamous cell carcinoma (ESCC). The current study aims to uncover novel miRNAs for prognostic biomarkers in ESCC patients. Patients and Methods: We initially screened the expression of 754 serum miRNAs using TaqMan Low Density Array in two pooled samples respectively from 28 ESCC and 28 normal controls. Markedly upregulated miRNAs in ESCC and some miRNAs reported to be differently expressed in ESCC tissue were then validated individually by RT-qPCR in another 83 patients and 83 controls arranged in two phases. The changes of the selected miRNAs during the esophagectomy and their prognostic value were examined. Results: Seven serum miRNAs were found to be significantly higher in ESCC than in controls; namely, miR-25, miR-100, miR-193-3p, miR-194, miR-223, miR-337-5p and miR-483-5p (P<0.0001), and the area under the receiver-operating-characteristic (ROC) curve (AUC) for the seven-miRNA panel was 0.83 (95% CI 0.75–0.90). Most of these miRNAs declined markedly in postoperative samples versus preoperative samples (P<0.05). Moreover, high level of miR-25 was significantly correlated with shorter overall survival in patients (P = 0.027). Cox regression analysis identified lymph node metastasis, miR-25 and miR-100 as the independent risk factors for overall survival (hazard ratio (HR) 2.98 [1.36–6.55], P = 0.006; HR 3.84 [1.02–14.41], P = 0.029; HR 4.18 [1.21–14.50], P = 0.024, respectively). Conclusion: The seven serum miRNAs could potentially serve as novel biomarkers for ESCC; moreover, specific miRNAs such as miR-25 and miR-100 can predict poor survival in ESCC. [ABSTRACT FROM AUTHOR]

Summary: Plants have evolved complex signalling networks to regulate growth and defence responses under an ever‐changing environment. However, the molecular mechanisms underlying the growth‐defence tradeoff are largely unclear. We previously reported that rice CALCIUM‐DEPENDENT PROTEIN KINASE 18 (OsCPK18) and MITOGEN‐ACTIVATED PROTEIN KINASE 5 (OsMPK5) mutually phosphorylate each other and that OsCPK18 phosphorylates and positively regulates OsMPK5 to suppress rice immunity. In this study, we found that OsCPK18 and its paralog OsCPK4 positively regulate plant height and yield‐related traits. Further analysis reveals that OsCPK18 and OsMPK5 synergistically regulate defence‐related genes but differentially regulate development‐related genes. In vitro and in vivo kinase assays demonstrated that OsMPK5 phosphorylates C‐terminal threonine (T505) and serine (S512) residues of OsCPK18 and OsCPK4, respectively. The kinase activity of OsCPK18T505D, in which T505 was replaced by aspartic acid to mimic T505 phosphorylation, displayed less calcium sensitivity than that of wild‐type OsCPK18. Interestingly, editing the MAPK phosphorylation motif in OsCPK18 and its paralog OsCPK4, which deprives OsMPK5‐mediated phosphorylation but retains calcium‐dependent activation of kinase activity, simultaneously increases rice yields and immunity. This editing event also changed the last seven amino acid residues of OsCPK18 and attenuated its binding with OsMPK5. This study presents a new regulatory circuit that fine tunes the growth‐defence tradeoff by modulating OsCPK18/4 activity and suggests that CRISPR/Cas9‐mediated engineering phosphorylation pathways could simultaneously improve crop yield and immunity. [ABSTRACT FROM AUTHOR]

Apple juice (AJ) was fermented by six select lactic acid bacteria (LAB), namely Lactobacillus plantarum 90 (Lp90), Lactobacillus helveticus 76 (Lh76), Lactobacillus casei 37 (Lc37), Lactobacillus paracasei 01 (Lpc01), Lactobacillus acidophilus 85 (La85) and Bifidobacterium lactis 80 (Bla80). The effects of LAB fermentation on sugars and organic acids contents, phenolic profiles, antioxidant capacity and flavor volatiles of fermented AJ (FAJ) were investigated. Results showed that AJ was an excellent food matrix for LAB strains. Lh76 and Lp90 showed the highest viable counts of 12.7 log CFU/mL at the end of fermentation. Lp90, La85 and Bla80 exhibited strong malolactic conversion capacity and finally produced lactic acid more than 6.5 mg/mL. In addtion, LAB fermentation significantly (p < 0.05) decreased the total phenols and flavonoids levels. However, antioxidant activities based on DPPH and FRAP methods were enhanced during fermentation, especially for La85 which exhibited dramatical DPPH radical scavenging activity (90.05%) and FRAP (0.96 mmol Trolox/L). The improvement of antioxidant activities was suggested to be related to the increase in caffeic acid and phlorizin contents. The analysis of flavor volatiles showed that LAB fermentation resulted in formation of seven new alcohols and six new esters, and improvement of ketones and aldehydes production. • Fuji apple juice was an excellent food matrix for select lactic acid bacteria. • Select lactic acid bacteria exhibited strong malolactic acid conversion capacity. • Antioxidant capacity of apple juice was increased by lactic acid fermentation. • Caffeic acid and phlorizin contents were increased by lactic acid fermentation. • Lactic acid fermentation improved the aroma complexity of apple juice. [ABSTRACT FROM AUTHOR]

In this work, nickel cobalt bimetallic sulfide with typical multi-shell hollow sphere structure behaved superior electrocatalytic activity towards hydrogen evolution reaction (HER), which have been prepared through a easy method included solvothermal step, calcination step and in-situ sulfurization step. The composition and structure of the obtained nickel cobalt bimetallic sulfide are controlled through adjusting the sulfurization temperature and dosage of sulfur source. The as-prepared Ni–Co-S multi-shell hollow microspheres (abbreviated as Ni-Co-S) behaves superb HER properties in alkaline medium and Ni-Co-S-340(60) performs the most superior property, in which reflected the lowest overpotential (129 mV vs. RHE) at the current density of 10 mA cm−2 and the smallest Tafel slope (96.1 mV dec−1) among all the synthesized samples. The superior electrocatalytic performance of the obtained Ni-Co-S-340(60) for HER is owing to the unique multi-shell hollow structure derived from the intrinsic porous character of Ni-Co-BTC MOF precursor in one hand. And in the other hand, introducing highly active NiCo 2 S 4 into NiS 2 would enhance its elctrocatalytic activity because of the strong interfacial effect between NiS 2 and NiCo 2 S 4. Image 1 [ABSTRACT FROM AUTHOR]

[Display omitted] • Electron beam irradiation inactivated Lactobacillus plantarum thoroughly. • High pressure processing increased extractable phenolics and carotenoids contents. • High pressure processing improved antioxidant capacity of fermented cabbage sauce. • Non-thermal processing was more beneficial to flavor formation than thermal. To extend shelf life of fermented spicy Chinese cabbage sauce at room temperature, the effects of electron beam irradiation (EBI), high pressure processing (HPP), pasteurization (PT) and autoclave sterilization (AS) treatments on the colony counts of Lactobacillus plantarum , phytochemicals, antioxidant activities and volatile compounds were investigated. Results showed that thermal and non-thermal treatments could significantly decrease the colony counts of Lactobacillus plantarum , in which EBI and AS treatments inactivated Lactobacillus plantarum thoroughly. EBI and HPP treatments were superior to PT and AS treatments in terms of volatile compounds, bioactive compounds and antioxidant activities. The total contents of volatile compounds in sauces treated by EBI and HPP were significantly increased by 43.92%–61.87% and 71.53%–84.46%, respectively, and the new formed substance 2,3-butanedione endowed sauces with sweet and creamy aroma. In addition, HPP treatment improved the extractable contents of total phenolics and carotenoids, retained capsicum red pigment content, and significantly enhanced antioxidant capacities of sauces. Sauce treated by HPP at 200 MPa exhibited the highest total carotenoid content, DPPH radical scavenging activity and FRAP, increasing by 9.27%, 2.24% and 16.13%, respectively, compared with CK. EBI treatment exhibited higher total phenolic content and FRAP, which positively depended on the dose. Therefore, HPP and EBI treatments were suggested as potential technologies to improve shelf-life stability and volatile compounds of fermented spicy Chinese cabbage sauce. [ABSTRACT FROM AUTHOR]

Background: Quantitative regional assessment of thoracic function would enable clinicians to better understand the regional effects of therapy and the degree of deviation from normality in patients with thoracic insufficiency syndrome (TIS). The purpose of this study was to determine the regional functional effects of surgical treatment in TIS via quantitative dynamic magnetic resonance imaging (MRI) in comparison with healthy children. Methods: Volumetric parameters were derived via 129 dynamic MRI scans from 51 normal children (November 2017 to March 2019) and 39 patients with TIS (preoperatively and postoperatively, July 2009 to May 2018) for the left and right lungs, the left and right hemi-diaphragms, and the left and right hemi-chest walls during tidal breathing. Paired t testing was performed to compare the parameters from patients with TIS preoperatively and postoperatively. Mahalanobis distances between parameters of patients with TIS and age-matched normal children were assessed to evaluate the closeness of patient lung function to normality. Linear regression functions were utilized to estimate volume deviations of patients with TIS from normality, taking into account the growth of the subjects. Results: The mean Mahalanobis distances for the right hemi-diaphragm tidal volume (RDtv) were −1.32 ± 1.04 preoperatively and −0.05 ± 1.11 postoperatively (p = 0.001). Similarly, the mean Mahalanobis distances for the right lung tidal volume (RLtv) were −1.12 ± 1.04 preoperatively and −0.10 ± 1.26 postoperatively (p = 0.01). The mean Mahalanobis distances for the ratio of bilateral hemi-diaphragm tidal volume to bilateral lung tidal volume (BDtv/BLtv) were −1.68 ± 1.21 preoperatively and −0.04 ± 1.10 postoperatively (p = 0.003). Mahalanobis distances decreased after treatment, suggesting reduced deviations from normality. Regression results showed that all volumes and tidal volumes significantly increased after treatment (p < 0.001), and the tidal volume increases were significantly greater than those expected from normal growth for RDtv, RLtv, BDtv, and BLtv (p < 0.05). Conclusions: Postoperative tidal volumes of bilateral lungs and bilateral hemi-diaphragms of patients with TIS came closer to those of normal children, indicating positive treatment effects from the surgical procedure. Quantitative dynamic MRI facilitates the assessment of regional effects of a surgical procedure to treat TIS. Level of Evidence: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Many essential oils have excellent insecticidal activity and have the potential to be developed as alternatives to chemical insecticides for pest control. Previously, we showed that β‐asarone, a major constituent of the essential oil derived from Acorus calamus L. (Acoraceae), has strong pesticidal activity against brown planthopper, Nilaparvata lugens (Stål) (Hemiptera: Delphacidae), the most notorious rice pest in Asia. Here, we report the first evaluation of the sublethal and transgenerational effects of β‐asarone on N. lugens. β‐Asarone significantly decreased female longevity, male longevity, fecundity, and hatchability of F0 generation individuals exposed to the LD30 and LD45 of β‐asarone relative to the acetone control. Moreover, compared with acetone, exposure to LD30 and LD45 of β‐asarone significantly shortened the duration of the egg stage, developmental duration of first instars, and female longevity of F1 generation individuals. Furthermore, the intrinsic rate of increase (r), finite rate of increase (λ), and net reproductive rates (R0) of insects treated with LD30 and LD45 of β‐asarone were significantly lower than those of insects treated with acetone. Compared with acetone, the fecundity and hatchability of F1 generation individuals were significantly decreased after exposure to β‐asarone at LD30 and LD45. These findings indicate the negative effects of sublethal doses of β‐asarone on N. lugens and provide novel information on the potential use of β‐asarone as a substitute chemical pesticide. [ABSTRACT FROM AUTHOR]

Triphenyltin chloride (TPTCL) is widely used in various industrial and agricultural applications. This study aimed to elucidate the mechanisms underlying the toxicological effects of TPTCL on oocytes. The obtained findings revealed that TPTCL exposure reduced polar body extrusion (PBE) and induced meiotic arrest. Mechanistically, TPTCL disrupted meiotic spindle assembly and chromosome alignment. Further analysis indicated a significant decrease in p-MAPK expression, and disturbances in the localization of Pericentrin and p-Aurora A in TPTCL exposed oocytes, which suggesting impaired microtubule organizing center (MTOC)function. Moreover, TPTCL exposure enhance microtubule acetylation and microtubule instability. Therefore, the spindle assembly checkpoint (SAC) remained activated, and the activity of the anaphase-promoting complex (APC) was inhibited, thereby preventing oocytes from progressing into the entering anaphase I (AI) stage. TPTCL exposure also augmented the actin filaments in the cytoplasm. Notably, mitochondrial function appeared unaffected by TPTCL, as evidenced indicated by stable mitochondrial membrane potential and ATP content. Furthermore, TPTCL treatment altered H3K27me2, H3K27me3 and H3K9me3 levels, suggesting changes in epigenetic modifications in oocytes. Taken together, our results suggest that TPTCL disrupts cytoskeleton assembly, continuously activates SAC, inhibits APC activity, and blocks meiotic progression, ultimately impair oocyte maturation. • TPTCL exposure compromises the meiotic maturation of mouse oocytes. • TPTCL exposure affects spindle assembly in mouse oocytes. • TPTCL exposure affects the localization of MTOC-associated proteins and reduces P-Mapk expression in mouse oocytes. • TPTCL exposure continuously activates of spindle assembly checkpoint in mouse oocytes. [ABSTRACT FROM AUTHOR]

[Display omitted] • Microfluidic electrospinning for synthesizing fucoxanthin-loaded core–shell nanofibers. • GZ12/ZFx nanofibers significantly enhance hydrophobicity and stability of fucoxanthin. • Fucoxanthin-loaded nanofibers alleviate lipid accumulation and oxidative stress in oleic acid-incubated HepG2 cells. Fucoxanthin is a xanthophyll carotenoid that possesses potent antioxidant, anti-obesity, and anti-tumor properties. However, its limited solubility in water and susceptibility to degradation create challenges for its application. In this study, a microfluidic coaxial electrospinning technique was used to produce core–shell zein-gelatin nanofibers for encapsulating fucoxanthin, enhancing its bioavailability, and improving its stability. In comparison to uniaxially-loaded fucoxanthin nanofibers, the encapsulation efficiency of fucoxanthin reached 98.58 % at a core–shell flow rate ratio of 0.26:1, representing a 14.29 % improvement. The photostability of the nanofibers increased by 74.59 % after three days, UV stability increased by 38.82 % after 2 h, and temperature stability also significantly improved, demonstrating a protective effect under harsh environmental conditions (P < 0.05). Additionally, nanofibers effectively alleviated oleic acid-induced reactive oxygen species production and reduced fluorescence intensity by 54.76 %. MTT experiments indicated great biocompatibility of the nanofibers, effectively mitigating mitochondrial membrane potential polarization and lipid accumulation in HepG2 cells. Overall, the microfluidic coaxial electrospinning technique enables promising applications of fucoxanthin delivery in the food industry. [ABSTRACT FROM AUTHOR]

This study investigated the effects of ultrasound-assisted phosphorylation on gelling properties of fish gelatin (FG). Ultrasound-assisted phosphorylation (UP) for 60, 90, and 120 min resulted in >6.54% increase of phosphorylation degree and decreased zeta potential of FG. Atomic force microscopy revealed that UP-FGs showed larger aggregates than P-FGs (normal phosphorylation FGs). Low frequent-NMR and microstructure analysis revealed that phosphorylation enhanced water-binding capability of FG and improved the gel networks. However, UP60 had the highest gel strength (340 g), gelling (17.96 °C) and melting (26.54 °C) temperature while UP90 and UP120 showed slightly lower of them. FTIR analysis indicated thatβ-sheet and triple helix content increased but random coil content decreased in phosphorylated FGs. Mass spectrometry demonstrated phosphate groups mainly bound to serine, threonine and tyrosine residues of FG and UP-FG exhibited more phosphorylation sites. The study showed that mild phosphorylation (UP60) could be applied to improve FG gel properties. [Display omitted] • Ultrasound assistance increased the phosphorylation degree and sites of FG. • Phosphate group mainly bound to serine, threonine and tyrosine residues of FG. • Moderate phosphorylation increased water binding ability, GS, GT and MT of FG. • Over phosphorylation led to poor gel network and gel properties of FG. [ABSTRACT FROM AUTHOR]

PD-L1 is an important immune checkpoint protein that can bind to T cells' PD-1 receptor, thereby promoting immune escape from tumors. In recent years, many researchers have developed strategies to degrade PD-L1 to improve the effect of immunotherapy. The study of degrading PD-L1 provides new opportunities for immunotherapy. Here, we mainly summarize and review the current active molecules and mechanisms that mediate the degradation of immature and mature PD-L1 during the post-translational modification stages, involving PD-L1 phosphorylation, glycosylation, palmitoylation, ubiquitination, and the autophagy-lysosomal process. This review expects that by degrading PD-L1 protein, we will not only gain a better understanding of oncogenic mechanisms involving tumor PD-L1 protein but also provide a new way to improve immunotherapy. [Display omitted] [ABSTRACT FROM AUTHOR]

The molecular mechanisms governing skin fibrosis in murine sclerodermatous graft-versus-host disease (Scl GVHD) are not known. We used Affymetrix DNA microarrays representing >14,000 mouse genes to characterize global gene expression in skin during development of Scl GVHD in lethally irradiated BALB/c (H-2d) mice transplanted with B10.D2 (H-2d) bone marrow and spleen cells. These mice develop skin thickening, whereas control mice transplanted with syngeneic BALB/c (H-2d) bone marrow and spleen cells do not develop disease. We found consistent differences between mice with Scl GVHD and controls in cytokine messenger RNAs (mRNAs) for both Th1-like (IFN-γ) and Th2-like (IL-6, Il-10, and IL-13) inflammatory patterns. mRNAs for chemokines CCL2, CCL5, CCL17, IFN-γ inducible chemokines (CXCL9/Mig, CXCL10/IP-10, and CXCL11/I-TAC), and for growth factors such as platelet-derived growth factor-c, connective tissue growth factor, fibroblast growth factor 1, epidermal growth factor, nerve growth factor-β, vascular endothelial growth factor (VEGF)-α, and VEGF-β were elevated, similar to human scleroderma. mRNAs for cell adhesion molecules, such as L-selectin (selectin lymphocyte), P-selectin (selectin platelet), E-selectin (selectin endothelium), and vascular cell adhesion molecule 1, were also upregulated. In separate experiments, we confirmed the increased synthesis of IFN-γ and IL-2, unchanged IL-10, and absence of tumor necrosis factor-α, and IL-4 proteins by flow cytometry of isolated skin T cells. These constellations of immunologic changes provide a “fingerprint” for fibrosing autoimmune disease. They are useful to understand the pathogenesis of Scl GVHD, to identify markers for early diagnosis of disease, and to devise more effective strategies for intervention in early scleroderma and Scl GVHD.Journal of Investigative Dermatology (2007) 127, 281–292. doi:10.1038/sj.jid.5700517; published online 17 August 2006 [ABSTRACT FROM AUTHOR]

We applied a set of in silico and in vitro assays, compliant with the Comprehensive In Vitro Proarrhythmia Assay (CiPA) paradigm, to assess the risk of chloroquine (CLQ) or hydroxychloroquine (OH‐CLQ)‐mediated QT prolongation and Torsades de Pointes (TdP), alone and combined with erythromycin (ERT) and azithromycin (AZI), drugs repurposed during the first wave of coronavirus disease 2019 (COVID‐19). Each drug or drug combination was tested in patch clamp assays on seven cardiac ion channels, in in silico models of human ventricular electrophysiology (Virtual Assay) using control (healthy) or high‐risk cell populations, and in human‐induced pluripotent stem cell (hiPSC)‐derived cardiomyocytes. In each assay, concentration‐response curves encompassing and exceeding therapeutic free plasma levels were generated. Both CLQ and OH‐CLQ showed blocking activity against some potassium, sodium, and calcium currents. CLQ and OH‐CLQ inhibited IKr (half‐maximal inhibitory concentration [IC50]: 1 µM and 3–7 µM, respectively) and IK1 currents (IC50: 5 and 44 µM, respectively). When combining OH‐CLQ with AZI, no synergistic effects were observed. The two macrolides had no or very weak effects on the ion currents (IC50 > 300–1000 µM). Using Virtual Assay, both antimalarials affected several TdP indicators, CLQ being more potent than OH‐CLQ. Effects were more pronounced in the high‐risk cell population. In hiPSC‐derived cardiomyocytes, all drugs showed early after‐depolarizations, except AZI. Combining CLQ or OH‐CLQ with a macrolide did not aggravate their effects. In conclusion, our integrated nonclinical CiPA dataset confirmed that, at therapeutic plasma concentrations relevant for malaria or off‐label use in COVID‐19, CLQ and OH‐CLQ use is associated with a proarrhythmia risk, which is higher in populations carrying predisposing factors but not worsened with macrolide combination. [ABSTRACT FROM AUTHOR]

The cytochrome P450 monooxygenases of insects play crucial roles in the metabolic detoxification of insecticides. Our previous finding showed that two cytochrome P450 genes, both CYP301B1 and CYP6AX1v2 , in the BPH underwent overexpression due to β-asarone. In this study, we investigated the molecular characteristics, expression patterns and functions of these two cytochrome P450 genes. The results showed that CYP301B1 had the highest expression level in the eggs, while CYP6AX1v2 was expressed in macropterous female adults. Moreover, the expression level of CYP301B1 in the head was higher than that in the integument, fat body and gut. The expression level of CYP6AX1v2 in the fat body and gut was higher than that in head and integument. Importantly, silencing CYP301B1 and CYP6AX1v2 separately could increase the sensitivity, resulting in significant higher mortality of BPH following treatment with β-asarone. Our findings indicated that CYP301B1 and CYP6AX1v2 could contribute to the resistance of BPH to β-asarone, and these two genes may be involved in the detoxification metabolism of β-asarone in BPH. • CYP301B1 is mainly expressed in the eggs, head and integument. • CYP6AX1v2 is mainly expressed in macropterous female adults and the fat body and gut. • Silencing CYP301B1 and CYP6AX1v2 could increase the sensitivity of BPH to β-asarone. [ABSTRACT FROM AUTHOR]

Background: A database of normative quantitative measures of regional thoracic ventilatory dynamics, which is essential to understanding better thoracic growth and function in children, does not exist.Research Question: How to quantify changes in the components of ventilatory pump dynamics during childhood via thoracic quantitative dynamic MRI (QdMRI)?Study Design and Methods: Volumetric parameters were derived via 51 dynamic MRI scans for left and right lungs, hemidiaphragms, and hemichest walls during tidal breathing. Volume-based symmetry and functional coefficients were defined to compare left and right sides and to compare contributions of the hemidiaphragms and hemichest walls with tidal volumes (TVs). Statistical analyses were performed to compare volume components among four age-based groups.Results: Right thoracic components were significantly larger than left thoracic components, with average ratios of 1.56 (95% CI, 1.41-1.70) for lung TV, 1.81 (95% CI, 1.60-2.03) for hemidiaphragm excursion TV, and 1.34 (95% CI, 1.21-1.47) for hemichest wall excursion TV. Right and left lung volumes at end-expiration showed, respectively, a 44% and 48% increase from group 2 (8 ≤ age < 10) to group 3 (10 ≤ age < 12). These numbers from group 3 to group 4 (12 ≤ age ≤ 14) were 24% and 28%, respectively. Right and left hemichest wall TVs exhibited, respectively, 48% and 45% increases from group 3 to group 4.Interpretation: Normal right and left ventilatory volume components have considerable asymmetry in morphologic features and dynamics and change with age. Chest wall and diaphragm contributions vary in a likewise manner. Thoracic QdMRI can provide quantitative data to characterize the regional function and growth of the thorax as it relates to ventilation. [ABSTRACT FROM AUTHOR]

The investigation and development of bimetallic phosphosulphide electrocatalyst with low cost and abundant reserves is extremely significant for the improvement of the efficiency of hydrogen evolution reaction (HER), while it remains a challenge. Herein, we explored a feasible method to prepare three-dimensional (3D) self-supported FeNiP-S/NF-5 nanosheet arrays on Ni foil (NF) by hydrothermal method and in situ phosphorization and following sulfurization treatment. The as-obtained FeNiP-S/NF-5 only needs a potential of 183 mV vs. RHE to reach 20 mA cm−2, which is smaller than that of FeNiP/NF (187 mV vs. RHE) and FeNiS/NF-5 (239 mV vs. RHE), presenting excellent electrocatalytic stability. Such outstanding performance of the FeNiP-S/NF-5 can be attributed to following several reasons: (i) bi-metallic phosphide and sulphide have the high intrinsic activity because of its synergistic effect; (ii) the 3D nanosheet arrays structure of FeNiP-S/NF-5 is conducive to expose plentiful active sites and facilitate the electrolyte penetration along with electron transportation; (iii) the sulfurization process followed phosphorization treatment could further optimize their electronic structure and inhibited the surface oxidation of catalyst in the catalytic process. Image 1 • NiS modified FeNiP nanosheet electrocatalyst have been synthesized. • The best condition of sulfurization treatment has also been investigated. • The 3D structure and the introduction of NiS can boost activity. [ABSTRACT FROM AUTHOR]

Bimetallic phosphides have been widely investigated as electrocatalysts for oxygen evolution reaction (OER) due to their efficient activity and environmental friendliness. While the reasonable design and controllable synthesis of bimetallic phosphide with typical nanostructure is still a great challenge. Hence, we put forward a novel and straightforward way for constructing FeP nanoparticles coated Ni 2 P ultrathin nanotube arrays on the surface of Ni foil (FeP@Ni 2 P/NF), which is synthesized through two steps of electrodeposition and subsequent in-situ phosphorization process. The obtained FeP@Ni 2 P/NF shows excellent electrochemical activity for OER, and it only needs potential of 1.52 V vs. RHE to reach the current density of 50 mA cm−2 in an alkaline media. The excellent electrocatalytic activity of FeP@Ni 2 P/NF mainly benefits from: (i) the synergistic effect between FeP and Ni 2 P promoting electron transfer; (ii) the formation of the unique 3D ultrathin nanotube arrays increasing the quantity of active sites and avoiding the agglomeration of catalysts during testing. In addition, the influence of reaction condition on the electrochemical activity for OER has also been investigated through altering the phosphorization temperature of precursor. Image 1 • The bimetallic phosphide was obtained through electrodeposition and phosphorization process. • The typical nanoparticle coated nanotube structure could expose more active sites. • Temperature of phosphorization treatment is a crucial factor to the enhanced activity. • The synergistic effective between FeP and Ni 2 P contributes to the excellent performance. [ABSTRACT FROM AUTHOR]

Obesity is associated with an increased risk of primary graft dysfunction (PGD) after lung transplantation. The contribution of specific adipose tissue depots is unknown. We performed a prospective cohort study of adult lung transplant recipients at 4 U.S. transplant centers. We measured cross-sectional areas of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) on chest and abdominal computed tomography (CT) scans and indexed each measurement to height.2 We used logistic regression to examine the associations of adipose indices and adipose classes with grade 3 PGD at 48 or 72 hours, and Cox proportional hazards models to examine survival. We used latent class analyses to identify the patterns of adipose distribution. We examined the associations of adipose indices with plasma biomarkers of obesity and PGD. A total of 262 and 117 subjects had available chest CT scans and underwent protocol abdominal CT scans, respectively. In the adjusted models, a greater abdominal SAT index was associated with an increased risk of PGD (odds ratio 1.9, 95% CI 1.02–3.4, p = 0.04) but not with survival time. VAT indices were not associated with PGD risk or survival time. A greater abdominal SAT index correlated with greater pre- and post-transplant leptin (r = 0.61, p < 0.001, and r = 0.44, p < 0.001), pre-transplant IL-1RA (r = 0.25, p = 0.04), and post-transplant ICAM-1 (r = 0.25, p = 0.04). We identified 3 latent patterns of adiposity. The class defined by high thoracic and abdominal SAT had the greatest risk of PGD. Subcutaneous, but not visceral, adiposity is associated with an increased risk of PGD after lung transplantation. [ABSTRACT FROM AUTHOR]

Highlights • Extension of the previous AAR framework for anatomy recognition to disease quantification. • Disease burden estimation on PET/CT images without explicit operations such as object delineation and partial volume correction but after only object localization and using fuzzy principles. • A general strategy that allows disease quantification at the organ or lesion level via automatic or interactive techniques for object localization. Abstract Purpose The derivation of quantitative information from images in a clinically practical way continues to face a major hurdle because of image segmentation challenges. This paper presents a novel approach, called automatic anatomy recognition-disease quantification (AAR-DQ), for disease quantification (DQ) on positron emission tomography/computed tomography (PET/CT) images. This approach explores how to decouple DQ methods from explicit dependence on object (e.g., organ) delineation through the use of only object recognition results from our recently developed automatic anatomy recognition (AAR) method to quantify disease burden. Method The AAR-DQ process starts off with the AAR approach for modeling anatomy and automatically recognizing objects on low-dose CT images of PET/CT acquisitions. It incorporates novel aspects of model building that relate to finding an optimal disease map for each organ. The parameters of the disease map are estimated from a set of training image data sets including normal subjects and patients with metastatic cancer. The result of recognition for an object on a patient image is the location of a fuzzy model for the object which is optimally adjusted for the image. The model is used as a fuzzy mask on the PET image for estimating a fuzzy disease map for the specific patient and subsequently for quantifying disease based on this map. This process handles blur arising in PET images from partial volume effect entirely through accurate fuzzy mapping to account for heterogeneity and gradation of disease content at the voxel level without explicitly performing correction for the partial volume effect. Disease quantification is performed from the fuzzy disease map in terms of total lesion glycolysis (TLG) and standardized uptake value (SUV) statistics. We also demonstrate that the method of disease quantification is applicable even when the "object" of interest is recognized manually with a simple and quick action such as interactively specifying a 3D box ROI. Depending on the degree of automaticity for object and lesion recognition on PET/CT, DQ can be performed at the object level either semi-automatically (DQ-MO) or automatically (DQ-AO), or at the lesion level either semi-automatically (DQ-ML) or automatically. Results We utilized 67 data sets in total: 16 normal data sets used for model building, and 20 phantom data sets plus 31 patient data sets (with various types of metastatic cancer) used for testing the three methods DQ-AO, DQ-MO, and DQ-ML. The parameters of the disease map were estimated using the leave-one-out strategy. The organs of focus were left and right lungs and liver, and the disease quantities measured were TLG, SUV Mean , and SUV Max. On phantom data sets, overall error for the three parameters were approximately 6%, 3%, and 0%, respectively, with TLG error varying from 2% for large "lesions" (37 mm diameter) to 37% for small "lesions" (10 mm diameter). On patient data sets, for non-conspicuous lesions, those overall errors were approximately 19%, 14% and 0%; for conspicuous lesions, these overall errors were approximately 9%, 7%, 0%, respectively, with errors in estimation being generally smaller for liver than for lungs, although without statistical significance. Conclusions Accurate disease quantification on PET/CT images without performing explicit delineation of lesions is feasible following object recognition. Method DQ-MO generally yields more accurate results than DQ-AO although the difference is statistically not significant. Compared to current methods from the literature, almost all of which focus only on lesion-level DQ and not organ-level DQ, our results were comparable for large lesions and were superior for smaller lesions, with less demand on training data and computational resources. DQ-AO and even DQ-MO seem to have the potential for quantifying disease burden body-wide routinely via the AAR-DQ approach. Graphic abstract Image, graphical abstract [ABSTRACT FROM AUTHOR]

Abstract Stable, earth-abundant and efficient electrocatalysts for overall water splitting are urgently needed. In this work, we have reported the synthesis of FeNiP/NC hollow microboxes (FeNiP/NC) based bifunctional electrocatalyst via the phosphorization process using rationally designed cube-type metal-organic framework (FeNi-MOF) as both the template and carbon source. The FeNiP/NC, which were obtained by assembling the uniform FeNiP nanoparticals together through N-doped carbon, manifests outstanding catalytic performances for both the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in KOH solution. Notably, FeNiP/NC displays exceptional activity when it was utilized as both anode and cathode toward overall water splitting with potential of 1.54 V at a current density of 10 mA cm−2 in alkaline electrolyte, which is much better than FeP/NC and Ni 2 P/NC electrocatalyst. More importantly, the improvement of the catalytic activities of FeNiP/NC mainly benefits from the well dispersion of FeNiP nanoparticles on the surface of carbon support, the large active surface area and the doping of N and C derived from organic ligands. In addition, the enhanced electrocatalytic performance of FeNiP/NC for OER is closely related with the in-situ formed surficial MOOH (M = Fe, Ni) active sites, which has been confirmed by X-ray photoelectron spectroscopy (XPS) analysis. Graphical abstract Image 1 Highlights • Uniform FeNiP nanoparticles assembled together through N-doped carbon based hollow microboxs have been synthesized. • FeNiP/NC was obtained using FeNi-MOF as precursor. • Hollow FeNiP/NC is a bifunctional electrocatalyst for HER and OER in alkaline media. • The MOOH (M = Fe, Ni) with high activity for OER have in-situ formed on the surface of FeNiP/NC. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are very attractive as carriers of active components due to their good immunological and their ability to penetrate the physiological barrier that synthetic delivery carriers cannot penetrate. However, the low secretion capacity of EVs limited its widespread adoption, let alone the lower yield of EVs loaded with active components. Here, we report a large-scale engineering preparation strategy of synthetic probiotic membrane vesicles for encapsulating fucoxanthin (FX-MVs), an intervention for colitis. Compared with the EVs naturally secreted by probiotics, the engineering membrane vesicles showed a 150-fold yield and richer protein. Moreover, FX-MVs improved the gastrointestinal stability of fucoxanthin and inhibited H 2 O 2 -induced oxidative damage by scavenging free radicals effectively (p < 0.05). The in vivo results showed that FX-MVs could promote the polarization of macrophages to M2 type, prevent the injury and shortening of colon tissue (p < 0.05), and improve the colonic inflammatory response. Consistently, proinflammatory cytokines were effectively suppressed after FX-MVs treatment (p < 0.05). Unexpectedly, such engineering FX-MVs could also reshape the gut microbiota communities and improve the abundance of short-chain fatty acids in the colon. This study lays a foundation for developing dietary interventions using natural foods to treat intestinal-related diseases. [ABSTRACT FROM AUTHOR]

The brain undergoes enormous changes during childhood. Little is known about how the brain develops to serve word processing. The objective of the present study was to investigate the maturational changes of word processing in children and adolescents using magnetoencephalography (MEG). Responses to a word processing task were investigated in sixty healthy participants. Each participant was presented with simultaneous visual and auditory word pairs in “match” and “mismatch” conditions. The patterns of neuromagnetic activation from MEG recordings were analyzed at both sensor and source levels. Topography and source imaging revealed that word processing transitioned from bilateral connections to unilateral connections as age increased from 6 to 17 years old. Correlation analyses of language networks revealed that the path length of word processing networks negatively correlated with age (r = −0.833, p < 0.0001), while the connection strength (r = 0.541, p < 0.01) and the clustering coefficient (r = 0.705, p < 0.001) of word processing networks were positively correlated with age. In addition, males had more visual connections, whereas females had more auditory connections. The correlations between gender and path length, gender and connection strength, and gender and clustering coefficient demonstrated a developmental trend without reaching statistical significance. The results indicate that the developmental trajectory of word processing is gender specific. Since the neuromagnetic signatures of these gender-specific paths to adult word processing were determined using non-invasive, objective, and quantitative methods, the results may play a key role in understanding language impairments in pediatric patients in the future. [ABSTRACT FROM AUTHOR]

Purpose: Overweight and underweight conditions are considered relative contraindications to lung transplantation due to their association with excess mortality. Yet, recent work suggests that body mass index (BMI) does not accurately reflect adipose tissue mass in adults with advanced lung diseases. Alternative and more accurate measures of adiposity are needed. Chest fat estimation by routine computed tomography (CT) imaging may therefore be important for identifying high-risk lung transplant candidates. In this paper, an approach to chest fat quantification and quality assessment based on a recently formulated concept of standardized anatomic space (SAS) is presented. The goal of the paper is to seek answers to several key questions related to chest fat quantity and quality assessment based on a single slice CT (whether in the chest, abdomen, or thigh) versus a volumetric CT, which have not been addressed in the literature. Methods: Unenhanced chest CT image data sets from 40 adult lung transplant candidates (age 58 ± 12 yrs and BMI 26.4 ± 4.3 kg/m2), 16 with chronic obstructive pulmonary disease (COPD), 16 with idiopathic pulmonary fibrosis (IPF), and the remainder with other conditions were analyzed together with a single slice acquired for each patient at the L5 vertebral level and mid-thigh level. The thoracic body region and the interface between subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in the chest were consistently defined in all patients and delineated using Live Wire tools. The SAT and VAT components of chest were then segmented guided by this interface. The SAS approach was used to identify the corresponding anatomic slices in each chest CT study, and SAT and VAT areas in each slice as well as their whole volumes were quantified. Similarly, the SAT and VAT components were segmented in the abdomen and thigh slices. Key parameters of the attenuation (Hounsfield unit (HU) distributions) were determined from each chest slice and from the whole chest volume separately for SAT and VAT components. The same parameters were also computed from the single abdominal and thigh slices. The ability of the slice at each anatomic location in the chest (and abdomen and thigh) to act as a marker of the measures derived from the whole chest volume was assessed via Pearson correlation coefficient (PCC) analysis. Results: The SAS approach correctly identified slice locations in different subjects in terms of vertebral levels. PCC between chest fat volume and chest slice fat area was maximal at the T8 level for SAT (0.97) and at the T7 level for VAT (0.86), and was modest between chest fat volume and abdominal slice fat area for SAT and VAT (0.73 and 0.75, respectively). However, correlation was weak for chest fat volume and thigh slice fat area for SAT and VAT (0.52 and 0.37, respectively), and for chest fat volume for SAT and VAT and BMI (0.65 and 0.28, respectively). These same single slice locations with maximal PCC were found for SAT and VAT within both COPD and IPF groups. Most of the attenuation properties derived from the whole chest volume and single best chest slice for VAT (but not for SAT) were significantly different between COPD and IPF groups. Conclusions: This study demonstrates a new way of optimally selecting slices whose measurements may be used as markers of similar measurements made on the whole chest volume. The results suggest that one or two slices imaged at T7 and T8 vertebral levels may be enough to estimate reliably the total SAT and VAT components of chest fat and the quality of chest fat as determined by attenuation distributions in the entire chest volume. [ABSTRACT FROM AUTHOR]

Purpose Dynamic or 4D imaging of the thorax has many applications. Both prospective and retrospective respiratory gating and tracking techniques have been developed for 4D imaging via CT and MRI. For pediatric imaging, due to radiation concerns, MRI becomes the de facto modality of choice. In thoracic insufficiency syndrome (TIS), patients often suffer from extreme malformations of the chest wall, diaphragm, and/or spine with inability of the thorax to support normal respiration or lung growth (Campbell et al., 2003, Campbell and Smith, 2007), as such patient cooperation needed by some of the gating and tracking techniques are difficult to realize without causing patient discomfort and interference with the breathing mechanism itself. Therefore (ventilator-supported) free-breathing MRI acquisition is currently the best choice for imaging these patients. This, however, raises a question of how to create a consistent 4D image from such acquisitions. This paper presents a novel graph-based technique for compiling the best 4D image volume representing the thorax over one respiratory cycle from slice images acquired during unencumbered natural tidal-breathing of pediatric TIS patients. Methods In our approach, for each coronal (or sagittal) slice position, images are acquired at a rate of about 200–300 ms/slice over several natural breathing cycles which yields over 2000 slices. A weighted graph is formed where each acquired slice constitutes a node and the weight of the arc between two nodes defines the degree of contiguity in space and time of the two slices. For each respiratory phase, an optimal 3D spatial image is constructed by finding the best path in the graph in the spatial direction. The set of all such 3D images for a given respiratory cycle constitutes a 4D image. Subsequently, the best 4D image among all such constructed images is found over all imaged respiratory cycles. Two types of evaluation studies are carried out to understand the behavior of this algorithm and in comparison to a method called Random Stacking – a 4D phantom study and 10 4D MRI acquisitions from TIS patients and normal subjects. The 4D phantom was constructed by 3D printing the pleural spaces of an adult thorax, which were segmented in a breath-held MRI acquisition. Results Qualitative visual inspection via cine display of the slices in space and time and in 3D rendered form showed smooth variation for all data sets constructed by the proposed method. Quantitative evaluation was carried out to measure spatial and temporal contiguity of the slices via segmented pleural spaces. The optimal method showed smooth variation of the pleural space as compared to Random Stacking whose behavior was erratic. The volumes of the pleural spaces at the respiratory phase corresponding to end inspiration and end expiration were compared to volumes obtained from breath-hold acquisitions at roughly the same phase. The mean difference was found to be roughly 3%. Conclusions The proposed method is purely image-based and post-hoc and does not need breath holding or external surrogates or instruments to record respiratory motion or tidal volume. This is important and practically warranted for pediatric patients. The constructed 4D images portray spatial and temporal smoothness that should be expected in a consistent 4D volume. We believe that the method can be routinely used for thoracic 4D imaging. [ABSTRACT FROM AUTHOR]

Purpose: There are several disease conditions that lead to upper airway restrictive disorders. In the study of these conditions, it is important to take into account the dynamic nature of the upper airway. Currently, dynamic magnetic resonance imaging is the modality of choice for studying these diseases. Unfortunately, the contrast resolution obtainable in the images poses many challenges for an effective segmentation of the upper airway structures. No viable methods have been developed to date to solve this problem. In this paper, the authors demonstrate a practical solution by employing an iterative relative fuzzy connectedness delineation algorithm as a tool. Methods: 3D dynamic images were collected at ten equally spaced instances over the respiratory cycle (i.e., 4D) in 20 female subjects with obstructive sleep apnea syndrome. The proposed segmentation approach consists of the following steps. First, image background nonuniformities are corrected which is then followed by a process to correct for the nonstandardness of MR image intensities. Next, standardized image intensity statistics are gathered for the nasopharynx and oropharynx portions of the upper airway as well as the surrounding soft tissue structures including air outside the body region, hard palate, soft palate, tongue, and other soft structures around the airway including tonsils (left and right) and adenoid. The affinity functions needed for fuzzy connectedness computation are derived based on these tissue intensity statistics. In the next step, seeds for fuzzy connectedness computation are specified for the airway and the background tissue components. Seed specification is needed in only the 3D image corresponding to the first time instance of the 4D volume; from this information, the 3D volume corresponding to the first time point is segmented. Seeds are automatically generated for the next time point from the segmentation of the 3D volume corresponding to the previous time point, and the process continues and runs without human interaction and completes in 10 s for segmenting the airway structure in the whole 4D volume. Results: Qualitative evaluations performed to examine smoothness and continuity of motions of the entire upper airway as well as its transverse sections at critical anatomic locations indicate that the segmentations are consistent. Quantitative evaluations of the separate 200 3D volumes and the 20 4D volumes yielded true positive and false positive volume fractions around 95% and 0.1%, respectively, and mean boundary placement errors under 0.5 mm. The method is robust to variations in the subjective action of seed specification. Compared with a segmentation approach based on a registration technique to propagate segmentations, the proposed method is more efficient, accurate, and less prone to error propagation from one respiratory time point to the next. Conclusions: The proposed method is the first demonstration of a viable and practical approach for segmenting the upper airway structures in dynamic MR images. Compared to registration-based methods, it effectively reduces error propagation and consequently achieves not only more accurate segmentations but also more consistent motion representation in the segmentations. The method is practical, requiring minimal user interaction and computational time. [ABSTRACT FROM AUTHOR]

• Significant brain areas are re-combined to form an epilepsy network in CAE. • Multi-focal source activity may indicate more brain areas are involved in seizures. • Imaging findings may provide a reference for clinical characteristics. Epilepsy is considered as a network disorder. However, it is unknown how normal brain activity develops into the highly synchronized discharging activity seen in disordered networks. This study aimed to explore the epilepsy brain network and the significant re-combined brain areas in childhood absence epilepsy (CAE). Twenty-two children with CAE were recruited to study the neural source activity during ictal-onset and interictal periods at frequency bands of 1–30 Hz and 30–80 Hz with magnetoencephalography (MEG) scanning. Accumulated source imaging (ASI) was used to analyze the locations of neural source activity and peak source strength. Most of the participants had more active source activity locations in the ictal-onset period rather than in the interictal period, both at 1–30 Hz and 30–80 Hz. The frontal lobe (FL), the temporo-parietal junction (T-P), and the parietal lobe (PL) became the main active areas of source activity during the ictal period, while the precuneus (PC), cuneus, and thalamus were relatively inactive. Some brain areas become more excited and have increased source activity during seizures. These significant brain regions might be re-combined to form an epilepsy network that regulates the process of absence seizures. The study confirmed that important brain regions are reorganized in an epilepsy network, which provides a basis for exploring the network mechanism of CAE development. Imaging findings may provide a reference for clinical characteristics. [ABSTRACT FROM AUTHOR]

• The proposed method constitutes a novel automatic strategy for computationally inferring respiratory phases via free-breathing MRI. No need for manual labeling or assistance. • The optical-flux idea as the respiration surrogate is robust as seen from the results. It offers a quantum improvement in performance compared to existing techniques. • Strategies for detecting abnormal cycles and aligning to one normal respiratory model are novel and natural. • The results have been fully evaluated with the 4 proposed evaluation methods for both spatial and temporal continuity of the constructed 4D image. Since real-time 4D dynamic magnetic resonance imaging (dMRI) methods with adequate spatial and temporal resolution for imaging the pediatric thorax are currently not available, free-breathing slice acquisitions followed by appropriate 4D construction methods are currently employed. Self-gating methods, which extract breathing signals only from image information without any external gating technology, have much potential for this purpose, such as for use in studying pediatric thoracic insufficiency syndrome (TIS). Patients with TIS frequently suffer from extreme malformations of the chest wall, diaphragm, and spine, leading to breathing that is very complex, including deep or shallow respiratory cycles. Existing 4D construction methods cannot perform satisfactorily in this scenario, and most are not fully automatic, requiring manual interactive operations. In this paper, we propose a novel fully automatic 4D image construction method based on an image-derived concept called flux to address these challenges. We utilized 25 dMRI data sets from 25 pediatric subjects with no known thoracic anomalies and 58 dMRI data sets from 29 patients with TIS where each patient had a dMRI scan before and after surgery. A time sequence of 80 slices are acquired at each sagittal location continuously at a rate of ~480 ms per slice under free-breathing conditions, with 30–40 sagittal locations across the chest for each subject depending on the thoracic size. In our approach, we first extract the breathing signal for each sagittal location based on the flux of the optical flow vector field of the body region from the image time series. Here, for each time point of respiratory phase, the net flux of the body region can be regarded as the flux going into or out of the body region, which we term Optical Flux (OFx). OFx provides a very robust representation of the real breathing motion of the thorax. OFx allows us to perform a full analysis of all respiratory cycles, extract only normal cycles in a robust manner, and map all extracted normal cycles on to one cosine respiration model for each sagittal location. Subsequently, we re-sample one normal cycle from the respiration model for each location independently. The normal cycle models associated with the different sagittal locations are finally composited to form the final constructed 4D image. We employ several metrics to evaluate the quality of the 4D construction results: E ie – error in locating time instants corresponding to end inspiration and end expiration; E to – deviation from correct temporal order in each detected normal cycle; E ss – deviation in spatial smoothness; and E sc – deviation from spatial continuity as scored by a reader. The means and standard deviations of these metrics for normal subjects and TIS patients are found to be, respectively: E ie : 0.25 ± 0.05 and 0.38 ± 0.16 in units of time instance (ideal value = 0); E to : 2.7% ± 2.3% and 1.8% ± 2% (ideal value = 0%); E ss : 0.5 ± 0.17 and 0.54 ± 0.25 in pixel units (ideal value = 0); E sc : 4.6 ± 0.48 and 4.56 ± 0.98 (score range: best = 5, worst = 1). The results show that the OFx method achieves excellent spatial and temporal continuity and its yield was 100% meaning that it successfully performed 4D construction on every data set tested. Compared to a recently published method, OFx is fully automatic requiring about 5 min of computational time per study starting from acquired dMRI scans. The method achieves high temporal and spatial continuity even on complex TIS data sets that include many abnormal respiratory cycles. A new 4D dMRI construction method based on the concept of optical flux is presented which is fully automatic and very robust in deriving respiratory signals purely from dynamic image sequences even when presented with complex breathing patterns due to severe disease conditions like TIS. Evaluations show that its accuracy is comparable to the variations found in manual annotations. An important characteristic of the method is that it is independent of the number of sagittal locations used in the construction process, which suggests that it is applicable to imaging techniques where data are acquired at only a few sagittal locations instead of the full width of the thorax. The method is not tied to any specific imaging modality, as demonstrated in this paper on not just dMRI but dynamic computed tomography (CT) as well. [Display omitted] [ABSTRACT FROM AUTHOR]

• Jujube juices were excellent food matrices for select lactic acid bacteria. • Total phenolic content of jujube juice was increased by lactic acid fermentation. • Antioxidant capacities of jujube juice were improved by lactic acid fermentation. • Lactic acid fermentation led the increase of caffeic acid and rutin. • Lactic acid fermentation improved the aroma complexity of jujube juice. The objective of this study was to investigate the effects of four commercial lactic acid bacteria (LAB), namely L. acidophilus , L. casei , L. helveticus and L. plantarum , on the phenolic profiles, antioxidant capacities and flavor profiles of jujube juices prepared from two crop varieties (Ziziphus Jujuba cv. Muzao and Hetian). Results showed that both jujube juices were excellent matrices for LAB growth with more than 11 log CFU/mL of viable counts at the end of fermentation. LAB fermentation dramatically increased total phenolic content, while decreased total flavonoid content of jujube juices. However, antioxidant capacities based on DPPH and FRAP methods were significantly improved by LAB fermentation and positively correlated with caffeic acid and rutin contents. Furthermore, a total of 74 volatile compounds were identified and increased in total content by LAB fermentation, which resulted in 22 and 19 new flavor volatiles formation in Muzao juice and Hetian juice, respectively. [ABSTRACT FROM AUTHOR]

In this work, phenolics and antioxidant activity (AOA) of Chinese organic hawthorn berry (Crataegus pinnatifida) infusion (OHBI, brewed at 100 °C for 5/10/15 min) and decoction (OHBD, kept boiling for 5/10/15/30 min) were investigated and their digestive fate was further assessed by in vitro gastrointestinal model (VGIM). Nine phenolic acids, six flavonoids and two procyanidins were detected by HPLC-ESI-MS/MS with the most abundant being procyanidins (1275 ± 9–1531 ± 2 μg/g). Hawthorn berry was a great food matrix for phenolics extraction by infusion (52.7–58.8%)/decoction (62.8–64.3%), and OHBD10 presented the highest amount of phenolics (4148 ± 20 μg/g). OHBD kept boiling for 5–15 min exhibited higher AOA than OHBD30 as longer boiling resulted in a greater loss of phenolics. Digestive stability of phenolics varied depending on their structure (phenolic acids > others), digestive phase (small intestinal > gastric) and existing form (bound > free). Overall, 28.2% of phenolics became available for absorption after VGIM, and chlorogenic acid, epicatechin and procyanidin B2 were still the predominant antioxidant contributors. Catechin displayed the highest digestive recovery (244.7%) whereas only 24.4–27.9% were found in the mentioned predominant contributors. Although phenolics decreased after VGIM, relevant AOA (66.5 ± 1.9–132 ± 4 μmol Trolox/g) was observed. OHBI and OHBD could be regarded as bio-accessible sources of antioxidant phenolics for the dietary supplement as well as potential applications in food/pharmaceutical/nutraceutical industries. • Hawthorn is a great food matrix for phenolics extraction by OHBI (52.7–58.8%)/OHBD (62.8–64.3%). • OHBD kept boiling for 5–15 min can obtain great amounts of antioxidant phenolics from hawthorn berry. • Though phenolics decreased after digestion, relevant AOA (66.50–132.82 μmol TE/g) was observed. • Digestive recovery (0–244.7%) of phenolics varied among compounds and digestion phase. • Hawthorn berry infusion and decoction are bio-accessible sources of antioxidant phenolics. [ABSTRACT FROM AUTHOR]

In response to the ongoing shift of the regulatory cardiac safety paradigm, a recent White Paper proposed general principles for developing and implementing proarrhythmia risk prediction models. These principles included development strategies to validate models, and implementation strategies to ensure a model developed by one lab can be used by other labs in a consistent manner in the presence of lab-to-lab experimental variability. While the development strategies were illustrated through the validation of the model under the Comprehensive In vitro Proarrhythmia Assay (CiPA), the implementation strategies have not been adopted yet. The proposed implementation strategies were applied to the CiPA model by performing a sensitivity analysis to identify a subset of calibration drugs that were most critical in determining the classification thresholds for proarrhythmia risk prediction. The selected calibration drugs were able to recapitulate classification thresholds close to those calculated from the full list of CiPA drugs. Using an illustrative dataset it was shown that a new lab could use these calibration drugs to establish its own classification thresholds (lab-specific calibration), and verify that the model prediction accuracy in the new lab is comparable to that in the original lab where the model was developed (lab-specific validation). This work used the CiPA model as an example to illustrate how to adopt the proposed model implementation strategies to select calibration drugs and perform lab-specific calibration and lab-specific validation. Generic in nature, these strategies could be generally applied to different proarrhythmia risk prediction models using various experimental systems under the new paradigm. [ABSTRACT FROM AUTHOR]

Cotton (Gossypium spp.) is an important economic crop and there is obvious heterosis in cotton, fertility has played an important role in this heterosis. However, the genes that exhibit critical roles in anther development and fertility are not well understood. Here, we report an acyl-CoA N-acyltransferase (EC2.3; GhACNAT) that plays a key role in anther development and fertility. Suppression of GhACNAT by virus-induced gene silencing in transgenic cotton (G. hirsutum L. cv. C312) resulted in indehiscent anthers that were full of pollen, diminished filaments and stamens, and plant sterility. We found GhACNAT was involved in lipid metabolism and jasmonic acid (JA) biosynthesis. The genes differentially expressed in GhACNAT-silenced plants and C312 were mainly involved in catalytic activity and transcription regulator activity in lipid metabolism. In GhACNAT-silenced plants, the expression levels of genes involved in lipid metabolism and jasmonic acid biosynthesis were significantly changed, the amount of JA in leaves and reproductive organs was significantly decreased compared with the amounts in C312. Treatments with exogenous methyl jasmonate rescued anther dehiscence and pollen release in GhACNAT-silenced plants and caused self-fertility. The GhACNAT gene may play an important role in controlling cotton fertility by regulating the pathways of lipid synthesis and JA biogenesis. [ABSTRACT FROM AUTHOR]