Postharvest ripening of newly harvested corn: Weakened interactions between starch and protein.

The effects of postharvest ripening of corn on the mechanisms of starch and protein interactions were investigated using molecular dynamics and several chemical substances. Sodium dodecyl sulfate (SDS) treatment all significantly affected the starch content, molecular weight of proteins, relative crystallinity, pasting characteristics and dynamic viscoelasticity in samples before and after postharvest ripening. In the corn that had not undergone postharvest ripening, there were also significant electrostatic interactions and hydrogen bonds between starch and protein. In addition, molecular dynamics had demonstrated that the forces between starch and protein in corn were mainly hydrophobic interactions, electrostatic interaction, and hydrogen bonds. Compared with zein, corn glutelin was more tightly bound to starch. The binding energy of starch to both proteins was reduced in after postharvest-ripened corn. This study laid a rationale for investigating the change mechanism of corn postharvest ripening quality and improving processing property and edible quality of corn.

Rapid identification of potential nonsteroidal anti-inflammatory drug overdose-induced liver toxicity and prediction of follow-up exposure: Integrating bioanalytical and population pharmacokinetic assay.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most frequently used drugs that can cause liver toxicity. The aim of this study was to integrate bioanalytical and population pharmacokinetic (PopPK) assay to rapidly screen and quantify the concentrations of NSAIDs in plasma and monitor clinical safety. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous quantification of acetaminophen (APAP), flurbiprofen (FLB), aspirin (ASP), and ibuprofen (IBP), four commonly used NSAIDs. The PopPK model of the signature toxicant was analyzed based on the published literature. The LC-MS/MS method was successfully validated and applied to determine NSAID concentrations in patient plasma samples. APAP, ASP, and IBP data were best fitted using a one-compartment model, and FLB data were best fitted using a two-compartment model. Bootstrapping and visual predictive checks suggested that a robust and reliable pharmacokinetic model was developed. A fast, simple, and sensitive LC-MS/MS method was developed and validated for determining APAP, FLB, ASP, and IBP in human plasma. Combined with the PopPK model, this method was applied to rapidly analyze the concentrations of NSAIDs in clinical samples from patients presenting to the emergency department with acute liver dysfunction and monitored NSAIDs clinical safety.

Characterization of Pediatric Rectal Absorption, Drug Disposition, and Sedation Level for Midazolam Gel Using Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling.

This study aims to explore and characterize the role of pediatric sedation via rectal route. A pediatric physiologically based pharmacokinetic-pharmacodynamic (PBPK/PD) model of midazolam gel was built and validated to support dose selection for pediatric clinical trials. Before developing the rectal PBPK model, an intravenous PBPK model was developed to determine drug disposition, specifically by describing the ontogeny model of the metabolic enzyme. Pediatric rectal absorption was developed based on the rectal PBPK model of adults. The improved Weibull function with permeability, surface area, and fluid volume parameters was used to extrapolate pediatric rectal absorption. A logistic regression model was used to characterize the relationship between the free concentrations of midazolam and the probability of sedation. All models successfully described the PK profiles with absolute average fold error (AAFE) < 2, especially our intravenous PBPK model that extended the predicted age to preterm. The simulation results of the PD model showed that when the free concentrations of midazolam ranged from 3.9 to 18.4 ng/mL, the probability of "Sedation" was greater than that of "Not-sedation" states. Combined with the rectal PBPK model, the recommended sedation doses were in the ranges of 0.44-2.08 mg/kg for children aged 2-3 years, 0.35-1.65 mg/kg for children aged 4-7 years, 0.24-1.27 mg/kg for children aged 8-12 years, and 0.20-1.10 mg/kg for adolescents aged 13-18 years. Overall, this model mechanistically quantified drug disposition and effect of midazolam gel in the pediatric population, accurately predicted the observed clinical data, and simulated the drug exposure for sedation that will inform dose selection for following pediatric clinical trials.

A Hand Gesture Recognition Strategy Based on Virtual-Dimension Increase of EMG.

The electromyography(EMG) signal is the biocurrent associated with muscle contraction and can be used as the input signal to a myoelectric intelligent bionic hand to control different gestures of the hand. Increasing the number of myoelectric-signal channels can yield richer information of motion intention and improve the accuracy of gesture recognition. However, as the number of acquisition channels increases, its effect on the improvement of the accuracy of gesture recognition gradually diminishes, resulting in the improvement of the control effect reaching a plateau. To address these problems, this paper presents a proposed method to improve gesture recognition accuracy by virtually increasing the number of EMG signal channels. This method is able to improve the recognition accuracy of various gestures by virtually increasing the number of EMG signal channels and enriching the motion intention information extracted from data collected from a certain number of physical channels, ultimately providing a solution to the issue of the recognition accuracy plateau caused by saturation of information from physical recordings. Meanwhile, based on the idea of the filtered feature selection method, a quantitative measure of sample sets (separability of feature vectors [SFV]) derived from the divergence and correlation of the extracted features is introduced. The SFV value can predict the classification effect before performing the classification, and the effectiveness of the virtual-dimension increase strategy is verified from the perspective of feature set differentiability change. Compared to the statistical motion intention recognition success rate, SFV is a more representative and faster measure of classification effectiveness and is also suitable for small sample sets.

The Brucella Effector Protein BspF Regulates Apoptosis through the Crotonylation of p53.

The Brucella type IV secretion system (T4SS) can promote the intracellular survival and reproduction of Brucella. T4SS secretes effector proteins to act on cellular signaling pathways to inhibit the host's innate immune response and cause a chronic, persistent Brucella infection. Brucella can survive in host cells for a long time by inhibiting macrophage apoptosis and avoiding immune recognition. The effector protein, BspF, secreted by T4SS, can regulate host secretory transport and accelerate the intracellular replication of Brucella. BspF has an acetyltransferase domain of the GNAT (GCN5-related N-acetyltransferases) family, and in our previous crotonylation proteomics data, we have found that BspF has crotonyl transferase activity and crotonylation regulation of host cell protein in the proteomics data. Here, we found that BspF attenuates the crotonylation modification of the interacting protein p53, which reduces the p53 expression through the GNAT domain. BspF can inhibit the transcription and protein expression of downstream apoptotic genes, thereby inhibiting host cell apoptosis. Additionally, the Brucella ΔbspF mutant stain promotes apoptosis and reduces the survival rate of Brucella in the cells. In conclusion, we identified that the T4SS effector protein BspF can regulate host cell apoptosis to assist Brucella in its long-term survival by attenuating crotonylation modification of p53 and decreasing p53 expression. Our findings reveal a unique mechanism of elucidating how Brucella regulates host cell apoptosis and promotes its proliferation through the secretion of effector proteins.

Safety, Pharmacokinetics, and Pharmacodynamics of Midazolam Gel After Rectal Administration in Healthy Chinese Subjects.

BACKGROUND AND OBJECTIVES: Midazolam rectal gel is a novel rectal formulation that may be a promising and potential alternative to oral administration for pediatric sedation. The objective of this study was to evaluate the safety, pharmacokinetics, pharmacodynamics, and absolute bioavailability of midazolam rectal gel in healthy Chinese subjects. METHODS: An open-label, single-dose, randomized, two-period, two-treatment, crossover clinical study was conducted in 22 healthy subjects (16 males and six females), each receiving 2.5 mg intravenous midazolam in one period and 5 mg midazolam rectal gel in another period (the dosages here were calculated as active midazolam). Safety, pharmacokinetic, and pharmacodynamic assessments were conducted throughout the study. RESULTS: All of the subjects completed both treatment periods. The formulation of rectal gel was well tolerated, with no serious adverse events occurring. After a single rectal dose of 5 mg midazolam rectal gel, it was absorbed rapidly with a median value of time to peak concentration (Tmax) of 1.00 h, and mean values of the peak concentration (Cmax) and area under the concentration-time curve (AUC0-t) of 37.2 ng/mL and 137 h·ng/mL, respectively. The absolute bioavailability of rectal gel was 59.7%. The rectal gel exhibited a relatively delayed onset but a more stable sedative effect and a longer duration when compared with intravenous midazolam. CONCLUSION: Midazolam rectal gel may be a feasible alternative with a high level of acceptance in pediatric sedation and enhanced bioavailability compared to an oral formulation. The modeling results may help to disclose out the exposure-response relationship of midazolam rectal gel and support the design of an escalating-doses study and pediatric extrapolation study. CLINICAL TRIAL REGISTRATION: The study was registered at http://www.chinadrugtrials.org.cn (No. CTR20192350).

Postharvest ripening of two varieties of corns: Structure, antioxidant activities and physicochemical properties of zein.

The newly harvested Jidan 66 (JD66) and Liangyu 99 (LY99) varieties of corns were stored for 56 days at constant temperature of 15 and 25 °C with relative humidity of 55%. The postharvest ripening resulted in more disordered secondary structure and less compact tertiary conformation of zein. The emulsifying activity and foaming stability reached maximum after storage of corns at 15 and 25 °C for 14 days, while the emulsifying stability and foaming capacity were the highest at two temperatures of storage for 7 days and 28 days, respectively. Furthermore, zein had the highest viscoelasticity as well as the strongest antioxidant activities after the storage of JD66 at two temperatures for 28 days and the storage of LY99 at 15 °C for 42 days and at 25 °C for 28 days. Therefore, appropriate postharvest ripening of corns changed the structure of zein, improving its antioxidant activities and physicochemical properties.

Thermo-acoustoelastic effect of Rayleigh wave: Theory and experimental verification.

Previous studies showed that the thermally-induced ultrasonic bulk wave velocity change could be used to measure acoustoelastic coefficients and third-order elastic constants of elastic materials. This method is naturally immune from the ambient temperature effect and has improved sensitivity and a simpler test setup than the conventional acoustoelastic test. However, Rayleigh wave is preferred for thick components or structures with only one accessible surface. In this work, the thermo-hyperelastic constitutive equation, along with acoustoelastic theory, is used to derive the expression of the thermo-acoustoelastic coefficient (TAEC) of Rayleigh wave. The numerical relationship between the TAEC of Rayleigh wave and Murnaghan constants (l, m and n) are given for common metals. The TAEC expressions for Rayleigh wave and shear wave are similar, and both are dominated by the constant m. The TAEC of Rayleigh wave was measured on an aluminum 6061 specimen using the thermal modulation experiment in a temperature range of 22 ∼35 °C. The measured TAEC shows good agreement with the theoretical calculation. Then the third-order elastic constants were calculated based on TAECs of bulk waves and Rayleigh wave.

Real Depth-Correction in Ground Penetrating RADAR Data Analysis for Bridge Deck Evaluation.

When ground penetrating radar (GPR) is used for the non-destructive evaluation of concrete bridge decks, the rebar reflection amplitudes should be corrected for rebar depths to account for the geometric spreading and material attenuation of the electromagnetic wave in concrete. Most current depth-correction methods assume a constant EM wave velocity in the entire bridge deck and correct GPR amplitudes based on the two-way travel time (TWTT) instead of the actual rebar depth. In this paper, we proposed a depth-correction algorithm based on the real rebar depths. To compare different depth-correction methods, we used gprMax software to simulate GPR signals in four models with various dielectric constants and conductivity. The comparison shows that the TWTT-based depth-correction method tends to over-correct GPR amplitudes so that underestimates the deterioration level of concrete decks at certain locations. Two depth-based correction methods are proposed that use migrated amplitudes and further normalize the corrected amplitude by rebar depth (attenuation rate). These methods are then applied to GPR data collected on two bridges, and the results were validated by other NDE methods and chloride concentration test.

Pharmacokinetic Interaction of Anaprazole, Amoxicillin and Clarithromycin after Single-Dose Simultaneous Administration and the Effect of Adding Bismuth on Their Pharmacokinetics in Healthy Male Chinese Subjects.

BACKGROUND AND OBJECTIVE: Helicobacter pylori-positive ulcers are treated with a proton pump inhibitor (PPI) + two antibiotics with/without bismuth. The objective of this study was to investigate the pharmacokinetic interaction of the novel PPI anaprazole, amoxicillin and clarithromycin with/without bismuth. METHODS: This single-centre, randomised, open-label phase 1 pharmacokinetic study included healthy Chinese male participants, comprising two cohorts (cohort 1, 4 × 4 crossover design; cohort 2, 2 × 2 crossover design). In cohort 1, 24 participants received four treatment cycles with a different treatment in each cycle; the washout period between cycles was 9 days. Participants were randomly assigned to one of the following four treatment sequences (1:1:1:1): anaprazole sodium enteric-coated tablet 20 mg monotherapy, amoxicillin 1000 mg monotherapy, clarithromycin 500 mg monotherapy, and a three-drug combination (anaprazole 20 mg, amoxicillin 1000 mg and clarithromycin 500 mg). During each treatment cycle, study drugs were administered twice daily for four consecutive days and once in the morning on the fifth day. Cohort 2 participants were administered a single dose of the three-drug combination and a single dose of a four-drug combination (three-drug combination + bismuth 0.6 g) with a washout period of 11 ± 2 days between treatments. Blood samples were collected for pharmacokinetic analysis. RESULTS: Twenty-nine of 32 enrolled participants (cohort 1, n = 24; cohort 2, n = 8) completed the study. There were no significant differences in exposure or time to reach maximum concentration (Tmax) between each single drug or the three-drug combination (cohort 1) or between the three- and four-drug combinations (cohort 1) for any of the drugs/metabolites. CONCLUSIONS: Dose adjustments for individual drugs are not necessary with combined dosing of anaprazole, amoxicillin, clarithromycin and bismuth.

Influence of modification methods on physicochemical and structural properties of soluble dietary fiber from corn bran.

Soluble dietary fiber (SDF), which is a component of dietary fibers exhibit many physiological functions, biological activity, and good gel forming ability. In this study, extraction of SDF from corn bran was evaluated using twin-screw extrusion and ultrasonic treatment and the combinations of the respective methods with dual enzyme hydrolysis. The monosaccharide compositions, molecular weight, physicochemical properties, and structural and functional characteristics were determined. The results showed that ultrasonic and twin-extrusion treatments significantly increased the SDF content from 2.42 to 4.58 and 6.54%, respectively. Dual enzyme hydrolysis further increased the SDF content. Modification treatment changed the monosaccharide composition, improved physicochemical and functional properties, such as water and oil holding capacity, nitrite adsorption, and antioxidative ability. In conclusion, physical modification combined with enzyme treatment distinctly improved the extraction yield, physicochemical and functional properties of SDF. Therefore, the modified SDF is suitable as a functional food additive.

Lysine Acylation Modification Landscape of Brucella abortus Proteome and its Virulent Proteins.

The myriad of posttranslational modifications (PTMs) of proteins that occur in all living cells are crucial to all kinds of biological processes. Brucella is an intracellular parasitic bacterium that can cause chronic diseases in both humans and livestock. To reveal the relationship between PTMs and the virulence and survival of Brucella, we described the first comprehensive multiple PTM-omics atlas of B. abortus 2308. Five PTMs involving lysine, namely 2-hydroxyisobutyrylation, succinylation, crotonylation, acetylation, and malonylation were identified. Nearly 2,000 modified proteins were observed, and these proteins took part in many biological processes, with a variety of molecular functions. In addition, we detected many significant virulence factors of Brucella among the modified proteins. 10 of the 15 T4SS effector proteins were detected with one or more PTMs. Moreover, abundant PTMs were detected in other typical virulence factors. Considering the role of PTMs in various biological processes of Brucella virulence and survival, we propose that the virulence of Brucella is associated with the PTMs of proteins. Taken together, this study provides the first global survey of PTMs in Brucella. This is a prospective starting point for further functional analysis of PTMs during the survival of Brucella in hosts, interpretation of the function of Brucella proteins, and elucidation of the pathogenic mechanism of Brucella.

MicroRNA-155 expression with Brucella infection in vitro and in vivo and decreased serum levels of MicroRNA-155 in patients with brucellosis.

Infection with Brucella is characterized by the inhibition of host immune responses. MicroRNA-155 (miR-155) has been implicated in the immune response to many diseases. In this study, its expression during Brucella 16M infection of macrophages and mice was analyzed. Expression of miR-155 was significantly induced in macrophages at 24 h post infection. Further, an analysis of infected mice showed that miR-155 was inhibited at 7 and 14 days but induced at 28 days. Interestingly, this trend in induction or inhibition was reversed at 7 and 14 days in 16M△virB-infected mice. This suggested that decreased expression of miR-155 at an early stage of infection was dependent on intracellular replication. In humans with brucellosis, serum levels of miR-155 were significantly decreased compared to those in individuals without brucellosis and healthy volunteers. Significant correlations were observed between serum level of miR-155 and serum anti-Brucella antibody titers and the sweating symptom. This effect suggests that Brucella interferes with miR-155-regulated immune responses via a unique mechanism. Taken together, data from this study indicate that Brucella infection affects miR-155 expression and that human brucellosis patients show decreased serum levels of miR-155.

Corrigendum: Global Lysine Crotonylation Alterations of Host Cell Proteins Caused by Brucella Effector BspF.

[This corrects the article DOI: 10.3389/fcimb.2020.603457.].

Physiologically based pharmacokinetic/pharmacodynamic modeling to evaluate the absorption of midazolam rectal gel.

OBJECTIVE: We aimed to 1) develop physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) models of a novel midazolam rectal gel in healthy adults, 2) assess the contribution of different physiologically relevant factors in rectal absorption, and 3) to provide supports for future clinical studies of midazolam rectal gel. METHODS: We developed the rectal PBPK model after built the intravenous and the oral PBPK model. Then, the physiological progress of rectal route was described in terms of the drug release, the rectal absorption and the particle first-pass elimination. Next, the validated PBPK model was combined with the sigmoid Emax PD model. This PBPK/PD model was used to identify the dose range and the critical parameters to ensure safety sedation. RESULTS: Based on the simulations, the recommended maximum dose for adults' sedation was 15 mg. And the retention time of midazolam rectal gel should be longer than 3 h to reach over 80% pharmacokinetics and pharmacodynamics effects. CONCLUSION: We successfully developed a PBPK/PD model for the midazolam rectal gel, which accurately described the PK/PD behavior in healthy adults and indicated the transit time of rectum was the most sensitive parameter for absorption. This PBPK/PD model would be expected to support the future clinical studies and pediatric application.

A Study on the Classification Effect of sEMG Signals in Different Vibration Environments Based on the LDA Algorithm.

Myoelectric prosthesis has become an important aid to disabled people. Although it can help people to recover to a nearly normal life, whether they can adapt to severe working conditions is a subject that is yet to be studied. Generally speaking, the working environment is dominated by vibration. This paper takes the gripping action as its research object, and focuses on the identification of grasping intentions under different vibration frequencies in different working conditions. In this way, the possibility of the disabled people who wear myoelectric prosthesis to work in various vibration environment is studied. In this paper, an experimental test platform capable of simulating 0-50 Hz vibration was established, and the Surface Electromyography (sEMG) signals of the human arm in the open and grasping states were obtained through the MP160 physiological record analysis system. Considering the reliability of human intention recognition and the rapidity of algorithm processing, six different time-domain features and the Linear Discriminant Analysis (LDA) classifier were selected as the sEMG signal feature extraction and recognition algorithms in this paper. When two kinds of features, Zero Crossing (ZC) and Root Mean Square (RMS), were used as input, the accuracy of LDA algorithm can reach 96.9%. When three features, RMS, Minimum Value (MIN), and Variance (VAR), were used as inputs, the accuracy of the LDA algorithm can reach 98.0%. When the six features were used as inputs, the accuracy of the LDA algorithm reached 98.4%. In the analysis of different vibration frequencies, it was found that when the vibration frequency reached 20 Hz, the average accuracy of the LDA algorithm in recognizing actions was low, while at 0 Hz, 40 Hz and 50 Hz, the average accuracy was relatively high. This is of great significance in guiding disabled people to work in a vibration environment in the future.

Ubiquitin-Modified Proteome of SARS-CoV-2-Infected Host Cells Reveals Insights into Virus-Host Interaction and Pathogenesis.

The outbreak of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed a serious threat to global public health. The mechanism of pathogenesis and the host immune response to SARS-CoV-2 infection are largely unknown. In the present study, we applied a quantitative proteomic technology to identify and quantify the ubiquitination changes that occur in both the virus and the Vero E6 cells during SARS-CoV-2 infection. By applying label-free, quantitative liquid chromatography with tandem mass spectrometry proteomics, 8943 lysine ubiquitination sites on 3086 proteins were identified, of which 138 sites on 104 proteins were quantified as significantly upregulated, while 828 sites on 447 proteins were downregulated at 72 h post-infection. Bioinformatics analysis suggested that SARS-CoV-2 infection might modulate host immune responses through the ubiquitination of important proteins, including USP5, IQGAP1, TRIM28, and Hsp90. Ubiquitination modification was also observed on 11 SAR-CoV-2 proteins, including proteins involved in virus replication and inhibition of the host innate immune response. Our study provides new insights into the interaction between SARS-CoV-2 and the host as well as potential targets for the prevention and treatment of COVID-19.

Nondestructive evaluation of steel-concrete composite structure using high-frequency ultrasonic guided wave.

Steel-concrete modular construction is increasingly used in nuclear structure construction. Conventional nondestructive testing methods are not able to detect internal concrete defects because the thick concrete wall is covered by steel plates. An ultrasonic guided method is proposed to detect honeycombs and voids around cross tie bars by using the tie bar as the waveguide. Guided wave dispersion curves are analyzed for the two-layer system (tie bar embedded in concrete). The high order longitudinal mode L(0,8) is selected as the working mode due to its lowest attenuation. Ultrasonic attenuations were measured on naked bars and bars embedded in concrete. Material damping coefficients of the steel bar were calibrated on the naked bar. Three tie bars with different bonding conditions in concrete (solid, with honeycomb and void) were tested at early age, 7 days and 110 days. The experimental results demonstrate that ultrasonic guided wave attenuation can be used to identify internal defect and evaluate the tie bar/concrete bonding condition at both early and late ages.

Global Lysine Crotonylation Alterations of Host Cell Proteins Caused by Brucella Effector BspF.

In Brucella spp., the type IV secretion system (T4SS) is essential for bacterial intracellular survival and inhibition of the host innate immune response. The Brucella T4SS secretes 15 different effectors to escape host immunity and promote intracellular replication. Among them, BspF has a GNAT-family acetyltransferase domain, implying its acetyltransferase activity. We confirmed that BspF has acetyltransferase activity (data not shown) and de-crotonyltransferase activity. However, BspF overexpressed in HEK-293T cells can also enhance octamer crotonylation in vitro. Then we enriched crotonylated proteins and conducted LC-MS to study the crotonylation changes of proteins in HEK-293T cells caused by BspF overexpression. A total of 5,559 crotonylation sites were identified on 1,525 different proteins, of which 331 sites on 265 proteins were significantly changed. We found that Rab9A and RAP1B in proteomics data have a great impact on Brucella survival, so we speculate that BspF may influence the function of host proteins by altering crotonylation, thereby promoting the intracellular propagation of Brucella.

SEMG Feature Extraction Based on StockwellTransform Improves Hand MovementRecognition Accuracy.

Feature extraction, as an important method for extracting useful information from surfaceelectromyography (SEMG), can significantly improve pattern recognition accuracy. Time andfrequency analysis methods have been widely used for feature extraction, but these methods analyzeSEMG signals only from the time or frequency domain. Recent studies have shown that featureextraction based on time-frequency analysis methods can extract more useful information fromSEMG signals. This paper proposes a novel time-frequency analysis method based on the Stockwelltransform (S-transform) to improve hand movement recognition accuracy from forearm SEMGsignals. First, the time-frequency analysis method, S-transform, is used for extracting a feature vectorfrom forearm SEMG signals. Second, to reduce the amount of calculations and improve the runningspeed of the classifier, principal component analysis (PCA) is used for dimensionality reduction of thefeature vector. Finally, an artificial neural network (ANN)-based multilayer perceptron (MLP) is usedfor recognizing hand movements. Experimental results show that the proposed feature extractionbased on the S-transform analysis method can improve the class separability and hand movementrecognition accuracy compared with wavelet transform and power spectral density methods.