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Glycosphingolipids participate in brain development, intestinal tract maturation, and defense against gut pathogens. Here, we performed a qualitative and quantitative comparison of milk glycosphingolipids from secretors and nonsecretors. Hydrophilic interaction chromatography-electrospray ionization-tandem mass spectrometry was employed, along with an internal standard, to resolve the complications presented by the fact that glycosphingolipids are structurally diverse, varying in glycan composition and ceramide. In total, 101 glycosphingolipids were detected, of which 76 were reported for the first time, including fucose-modified neutral glycosphingolipids. Seventy-eight glycosphingolipids differed significantly between secretor and nonsecretor milk (p< 0.05), resulting in higher levels of certain neutral species (p< 0.001) but lower levels of fucose-modified monosialylated and disialylated species in secretor mothers (p< 0.01). In both milk types, the most abundant glycosphingolipids were of the monosialylated type, followed by disialylated, neutral, and trisialylated ones. Notably, fucose-modified monosialylated glycosphingolipids accounted for the highest proportion.

We report the development of a novel method for the synthesis of Azoxystrobin, which employs trimethylamine as a catalyst. This appealing catalytic system offers several advantages, including low cost, excellent reactivity, easy recovery, and the ability to be used repeatedly with minimal environmental impact. Mechanistic studies and density functional theory (DFT) calculations suggest that the involvement of a highly active quaternary ammonium salt intermediate is likely responsible for the efficient catalysis. This can be attributed to the low steric hindrance, flexible bare nature of the lone pair of electrons on the nitrogen atom, and low activation energy barrier of trimethylamine. These findings hold great promise for the mass production of Azoxystrobin.

Introduction:Phosphatase and tensin (PTEN) is a multifunctional gene associated with the normal development and physiological function of various tissues including the kidney. However, its role in renal tubular reabsorption function has not been well elucidated. Methods:We generated a renal tubule-specific Ptenknockout mouse model by crossing Ptenfl/fl mice with Ksp-Cretransgenic mice, evaluated the effect of Ptenloss on renal tubular function, and investigated the underlying mechanisms. Results:Ptenloss resulted in abnormal renal structure and function and water retention in multiple organs. Our results also demonstrated that aquaporin-2 (AQP2), an important water channel protein, was upregulated and concentrated on the apical plasma membrane of collecting duct cells, which could be responsible for the impaired water balance in Ptenloss mice. The regulation of Ptenloss on AQP2 was mediated by protein kinase B (AKT) activation. Conclusions:Our results reveal a connection between PTENgene inactivation and water retention, suggesting the importance of PTEN in normal kidney development and function.

This article studies the prescribed performance fault-tolerant control problem for a class of uncertain nonlinear multi-input and multioutput systems. A learning-based fault-tolerant controller is proposed to achieve the asymptotic stability, without requiring a priori knowledge of the system dynamics. To deal with the prescribed performance, a new error transformation function is introduced to convert the constrained error dynamics into an equivalent unconstrained one. Under the actor–critic learning structure, a continuous-time long-term performance index is presented to evaluate the current control behavior. Then, a critic network is used to approximate the designed performance index and provide a reinforcement signal to the action network. Based on the robust integral of the sign of error feedback control method, an action network-based controller is developed. It is shown by the Lyapunov approach that the tracking error can converge to zero asymptotically with the prescribed performance guaranteed. Simulation results are provided to validate the feasibility and effectiveness of the proposed control scheme.

This study investigated the effect of plant polysaccharides on the conformation and gel properties of the eugenol (Eu)-myofibrillar protein (MP) complex. Adding 0.5% inulin (I) and konjac glucomannan (K), which are two plant polysaccharides, to the Eu-MP complex lead to the inhibition of the Eu–MP interaction, which significantly increased carbonyl and thiol contents and surface hydrophobicity. Both polysaccharides significantly inhibited the reduction in the α-helix content (Eu-MP: 14.95%; Eu-MP-I: 18.04%; Eu-MP-K: 19.92%), thereby maintaining hydrogen bond stability in the protein. I and K significantly increased the strength of the complex gel and the storage modulus. Additionally, I and K promoted the formation of a denser gel structure of the Eu-MP complex, which significantly decreased moisture migration and the cooking loss of the gel. This study thus provides a theoretical basis for adding polysaccharide to inhibit the polyphenol–protein interaction so as to enhance the functional properties of proteins, as well as the practical application of polyphenols and polysaccharides in meat product processing.

Cinnamic acid (CA) and cinnamaldehyde (CMA) are essential components of the spice cinnamon, a commonly used food oxidizer and preservative. In this work, the binding mechanism and structural information of CA/CMA to bovine haemoglobin (BHb) were investigated through multi-spectroscopic and molecular simulation experiments focusing on assessing the effect of phytochemicals in spices on BHb. Fluorescence and isothermal titration calorimetry experiments showed that CA possessed a binding constant of 105 L/mol and an electrostatic interaction with BHb resulting in the formation of stable complexes compared to CMA-BHb. Spectroscopic results (UV–Vis, CD and synchrotron fluorescence experiments) demonstrated that the addition of CA/CMA differently altered or affected the polarity of the BHb microenvironment, slightly perturbing the secondary structure of BHb. Thermodynamic analyses and molecular docking data were analyzed to confirm the dominance of van der Waals and hydrogen bonding forces in the energy contribution of the CMA-BHb system, and molecular dynamics simulations demonstrated that CA/CMA was relatively stable in the hydrophobic pocket of the protein (BHb). These findings will provide a basis for applying phytochemicals in spices in meat processing.

In this paper, a SrAl2Si2O8:Tm3+,Yb3+upconversion (UC) phosphor was prepared with a high-temperature solid-phase method, and proved that the strontium feldspar structure was an excellent UC matrix. The Tm3+were shown to have a maximum relative thermometric sensitivity (Sr) of 1.67% K−1at 298 K and a maximum absolute thermometric sensitivity (Sa) of 1.34% K−1at 573 K. The non-thermally coupled energy level corresponded to the maximum relative thermometry sensitivity (Sr) of 2.4% K−1at 298 K and a maximum absolute sensitivity (Sa) of 13% K−1at 423 K. The use of the fluorescence intensity ratio of the nonthermally coupled energy levels of Tm3+for temperature measurements improved the temperature measurement sensitivity of the same material. These results indicated that the phosphor has good temperature sensing performance with a wide sensing range and good stability and has potential thermometry applications in the first biological window.

A novel proportional and delayed integral (PdI) transformation is proposed that recasts the cooperative control problem with communication delay to a simpler regulation problem. The PdI transformation enables the use of classical control techniques for solving leaderless consensus problems. Following this approach, we address for the first time the problem of leaderless consensus of heterogeneous multiagent systems in unknown pure-feedback form with state and communication time-delays and unknown disturbances. A general form of state delays is studied, which includes time-varying and distributed state delays among others. Retarded functional differential equations formalism is adopted in order to allow agent dynamics with such general state delays. The proposed algorithm guarantees that all closed-loop signals remain uniformly bounded and that the multiagent system achieves approximate consensus with prescribed steady-state error. Numerical simulations on a swarm of unmanned aerial vehicles verify the validity of the theoretical analysis.

This article proposes an adaptive neural network (NN) distributed control algorithm for a group of high-order nonlinear agents with nonidentical unknown control directions (UCDs) under signed time-varying topologies. An important lemma on the convergence property is first established for agents with antagonistic time-varying interactions, and then by using Nussbaum-type functions, a new class of NN distributed control algorithms is proposed. If the signed time-varying topologies are cut-balanced and uniformly in time structurally balanced, then convergence is achieved for a group of nonlinear agents. Moreover, the proposed algorithms are adopted to achieve the bipartite consensus of high-order nonlinear agents with nonidentical UCDs under signed graphs, which are uniformly quasi-strongly $\delta $ -connected. Finally, simulation examples are given to illustrate the effectiveness of the NN distributed control algorithms.

In this paper the distributed asymptotic consensus problem is addressed for a group of high-order nonaffine agents with uncertain dynamics, nonvanishing disturbances and unknown control directions under directed networks. A class of auxiliary variables are first introduced which forms second-order filters and induces all measurable signals of agents' states. In view of this property, a distributed robust integral of the sign of the error (DRISE) design combined with the Nussbaum-type function is presented that guarantees not only the desired asymptotic consensus, but also the uniform boundedness of all closed-loop variables. Compared with the traditional sliding mode control (SMC) technique, the main feature of our approach is that the integral operation in the proposed control algorithm is designed to be adopted in a continuous manner and ensures less chattering behavior. Simulation results for a group of Duffing-Holmes chaotic systems are employed to verify our theoretical analysis.

In this paper, we study the consensus problem for a class of linear multi-agent systems &#x0028 MASs &#x0029 with consideration of input saturation under the self-triggered mechanism. In the context of discrete-time systems, a self-triggered strategy is developed to determine the time interval between the adjacent triggers. The triggering condition is designed by using the current sampled consensus error. Furthermore, the consensus control protocol is designed by means of a state feedback approach. It is shown that the considered multi-agent systems can reach consensus with the presented algorithm. Some sufficient conditions are proposed in the form of linear matrix inequalities &#x0028 LMIs &#x0029 to show the positively invariant property of the domain of attraction &#x0028 DOA &#x0029 . Moreover, some sufficient conditions of controller synthesis are provided to enlarge the volume of the DOA and obtain the control gain matrix. A numerical example is simulated to demonstrate the effectiveness of the theoretical analysis results.

Genipin, a natural electrophilic cross-linker, was applied (5, 10, 20, and 30 mM) to modify hempseed protein isolate (HPI). Genipin treatments resulted in general losses of total sulfhydryls (up to 2.9 nmol/mg) and free amines (up to 77.3 nmol/mg). Surface hydrophobicity decreased by nearly 90% with 30 mM genipin, corresponding to similar tryptophan fluorescence quenching. The genipin treatment converted HPI into highly cross-linked polymers. Hydrogels formed with such polymers when also incorporated with hemp oil emulsions exhibited substantially enhanced gelling ability: up to 3.3- and 2.6-fold increases, respectively, in gel strength and gel elasticity over genipin-untreated protein. The genipin-modified composite gels also exhibited superior water-holding capacity. Microstructural analysis revealed a compact gel network filled with protein-coated oil globules that interacted intimately with the protein matrix when treated with genipin. Such gels remained readily digestible. Hence, genipin-treated hemp protein hydrogels show promise as functional food components.

One of the promising approaches to meet the urgent demand for further device miniaturization is to create functional devices using single molecules. Although various single-molecule electronic devices have been demonstrated recently, single-molecule optical devices which use external stimulations to control the optical response of a single molecule have rarely been reported. Here, we propose and demonstrate a field-effect Raman scattering (FERS) device with a single molecule, an optical counterpart to field-effect transistors (a key component of modern electronics). With our devices, the gap size between electrodes can be precisely adjusted at subangstrom accuracy to form single molecular junctions as well as to reach the maximum performance of Raman scattering via plasmonic enhancement. Based on this maximum performance, we demonstrated that the intensity of Raman scattering can be further enhanced by an additional ∼40% if the orbitals of the molecules bridged two electrodes were shifted by a gating voltage. This finding not only provides a method to increase the sensitivity of Raman scattering beyond the limit of plasmonic enhancement, but also makes it feasible to realize addressable functional FERS devices with a gate electrode array.

Alkaline pH12shift treatment performed at varying temperatures (20–80 °C for 1, 5, and 60 min) was applied to structurally modify hemp seed protein isolate (HPI). The solubility of HPI (∼20%) was remarkably improved (p< 0.05) with elevating the temperature and prolonging the holding time, reaching 97.5% at 80 °C for 60 min. The treated HPI exhibited a strong tendency of forming soluble large aggregates. To limit lysinoalanine (LAL) production, heating was methodically controlled to 60 °C and 5 min, where the LAL content never exceeded 100 mg/100 g of protein and the loss of cysteine and lysine was also minimal. The emulsifying activity of HPI was improved by this mild pH shift–heating combination treatment as a result of the dissociation of protein subunits, unraveling of the tertiary structure, and exposure of hydrophobic groups. Moreover, the emulsion formed by the treated protein maintained a superior stability in particle size and distribution during storage.

•Alkaline or acid pH shift alters protein structures.•pH shift processes improve surface properties of legume proteins.•pH shift treated soy and pea proteins are excellent emulsifiers.

Covalent complexes of bovine bone proteins (BBP) with four polyphenols (chlorogenic acid (CA), quercetin (Q), rutin (R), epigallocatechin gallate (EGCG)) with were prepared to increase the high-value utilization degree of bovine bone. The differences in coupling effect and structural and functional properties between the conjugates were also investigated. The results showed that EGCG-BBP had the highest polyphenolic equivalent at 88.05 mg/g protein and the lowest sulfhydryl group content. EGCG-BBP also had the best covalent effect. The SDS-PAGE and fluorescence spectra results revealed that the molecular weight of the conjugates increased significantly as different polyphenols conjugated with the aromatic amino acids in BBP, resulting in significant changes in the structure of EGCG-BBP. Fourier Transform infrared spectroscopy (FTIR) analysis demonstrated that the amide I band of conjugates was slightly shifted, indicating that the polyphenols were covalently bonded with BBP. Based on the results of this study and well-established mechanisms, it could be speculated that the best covalent effect of EGCG may be not only due to the eight phenolic hydroxyl groups but also to its two benzene rings, which are greatly increased in its reaction site. In terms of functional characteristics, EGCG-BBP had the highest 1-diphenyl-2-picryl-hydrazyl radical (DPPH·) scavenging capacity, while Q-BBP had the best solubility. Thus, this study provides a theoretical basis for different polyphenols' structural and functional effects on covalently modified proteins.

Endemic arsenism, caused by burning coal containing high levels of arsenic, is found only in the Guizhou and Shanxi Provinces of China. Dysregulated microRNAs (miRNAs), detected in the blood, are emerging as promising biomarkers. At present, little is known about the change and clinical efficacy of circulating miRNAs in patients with endemic arsenism produced by burning of coal. Here, we determined, by using TaqMan Human miRNA Array Chips, the differential expression of plasma miRNAs between patients with arsenism caused by coal-burning and a control group. Four increased miRNAs (miR-21, miR-145, miR-155, and miR-191) were verified in a larger sample by quantitative real-time PCR. Furthermore, bioinformatics and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to associate changes in plasma levels of the miRNAs with their functions and their effects on various pathways. The results of chip array assays show that the levels of miR-21, miR-141, miR-148a, miR-145, miR-155, miR-191, miR-218, and miR-491 were most prominently increased and that the levels of miR-200b, miR-200c, miR-26, and miR-34c were decreased. The qRT-PCR results confirm that the circulating levels of miR-21, miR-145, miR-155, and miR-191 are increased in patients with arsenism caused by coal-burning. KEGG analyses show that these miRNAs inhibit the target genes of pathways related to immune inflammation, oxidative stress, and DNA damage repair. Therefore, the four miRNAs may be biomarkers of endemic arsenism caused by coal-burning. Further studies with larger samples should be performed to confirm these findings and to elucidate the underlying mechanisms.

•Significant discordance in fibrosis staging between TE and LB:52.9% NAFLD patients•Higher discordance in F2 (66.3%) and F3 (60.4%) stages, lowest in F4 (0%)•BMI and T2DM associated with M-probe overestimation in fibrosis staging

Abstract

Utilizing individual atoms or molecules as functional units in electronic circuits meets the increasing technical demands for the miniaturization of traditional semiconductor devices. To be of technological interest, these functional devices should be high-yield, consume low amounts of energy, and operate at room temperature. In this study, we developed nanodevices called quantized conductance atomic switches (QCAS) that satisfy these requirements. The QCAS operates by applying a feedback-controlled voltage to a nanoconstriction within a stretched nanowire. We demonstrated that individual metal atoms could be removed from the nanoconstriction and that the removed metal atoms could be refilled into the nanoconstriction, thus yielding a reversible quantized conductance switch. We determined the key parameters for the QCAS between the “on” and “off” states at room temperature under a small operating voltage. By controlling the applied bias voltage, the atoms can be further completely removed from the constriction to break the nanowire, generating single-atom nanogaps. These atomic nanogaps are quite stable under a sweeping voltage and can be readjusted with subangstrom accuracy, thus fulfilling the requirement of both reliability and flexibility for the high-yield fabrication of molecular devices.

Graphical AbstractArsenic is a well established human carcinogen that causes diseases of the lung.Arsenic is a well established human carcinogen that causes diseases of the lung. Some studies have suggested that hypoxia-inducible factors (HIFs) and microRNAs (miRNAs) are involved in human lung cancer; however, their molecular mechanisms that causally contribute to arsenite-caused malignant transformation of cells remain unclear. To elucidate the mechanisms of angiogenesis and metastasis of lung cancer caused by arsenite, we investigated the role of HIF-2α regulation of miRNA-191 (miR-191) in the angiogenic and metastatic properties of human bronchial epithelial (HBE) cells transformed by arsenite. In HBE cells, HIF-2α binds to the hypoxia response element (HRE) in the promoter region of miR-191 and initiates transcription of miR-191. Blocking of HIF-2α with siRNA inhibited the up-regulation of miR-191, Wilms’ tumor 1 (WT1) protein, matrix metalloproteinase 9 (MMP-9), vascular endothelial growth factor (VEGF), and the down-regulation of brain acid-soluble protein 1 (BASP1). In arsenite-transformed HBE (T-HBE) cells, down-regulation of HIF-2α by siRNA blocked the process of angiogenesis and decreased their neoplastic properties and metastatic capacity, which were reversed by over-expression of miR-191 or by up-regulating WT1. Thus, HIF-2α up-regulates WT1 viamiR-191, both of which are involved in the angiogenesis and metastasis of T-HBE cells. The results present a better understanding of the processes involved in lung cancer caused by arsenite exposure.

A series of Tb3+, Eu3+, Li+co-doped SrSiO3phosphors were prepared using the high-temperature solid-phase method. The X-ray diffraction results showed that Tb3+and Eu3+successfully entered into the SrSiO3matrix lattice. Strong energy transfer from Tb3+to Eu3+is exhibited with a calculated energy transfer efficiency of 94.7%. Doping of the charge compensator Li+increased the luminescence intensity of the SrSiO3:6%Tb3+, 6%Eu3+, 3%Li+phosphor at a wavelength of 614 nm by 4.2 times and significantly improved the color purity of this phosphor (Cp= 85.9%). Based on color coordinate analysis, the phosphor color coordinates are located near (0.615, 0.365), which belongs to the red region. The phosphor was integrated into a white LED. The resultant package exhibited a color temperature of 6479 K and a color rendering index of 93.8. Its luminous performance was also very stable under different drive currents.

Arsenic is a well established human carcinogen that causes diseases of the lung. Some studies have suggested that hypoxia-inducible factors (HIFs) and microRNAs (miRNAs) are involved in human lung cancer; however, their molecular mechanisms that causally contribute to arsenite-caused malignant transformation of cells remain unclear. To elucidate the mechanisms of angiogenesis and metastasis of lung cancer caused by arsenite, we investigated the role of HIF-2α regulation of miRNA-191 (miR-191) in the angiogenic and metastatic properties of human bronchial epithelial (HBE) cells transformed by arsenite. In HBE cells, HIF-2α binds to the hypoxia response element (HRE) in the promoter region of miR-191 and initiates transcription of miR-191. Blocking of HIF-2α with siRNA inhibited the up-regulation of miR-191, Wilms’ tumor 1 (WT1) protein, matrix metalloproteinase 9 (MMP-9), vascular endothelial growth factor (VEGF), and the down-regulation of brain acid-soluble protein 1 (BASP1). In arsenite-transformed HBE (T-HBE) cells, down-regulation of HIF-2α by siRNA blocked the process of angiogenesis and decreased their neoplastic properties and metastatic capacity, which were reversed by over-expression of miR-191 or by up-regulating WT1. Thus, HIF-2α up-regulates WT1 viamiR-191, both of which are involved in the angiogenesis and metastasis of T-HBE cells. The results present a better understanding of the processes involved in lung cancer caused by arsenite exposure.

The attitude coordinated tracking problem of multiple spacecraft with control input saturation is studied in this paper. We first construct a decentralized attitude coordinated tracking algorithm with input saturation, such that spacecraft can track a time-varying desired trajectory and align their attitudes. We then introduce a novel auxiliary dynamical systems to present an attitude coordinated tracking algorithm with input saturation and without angular velocity measurements. Throughout this paper, the information flow between spacecraft is assumed to be undirected. Finally, design examples are given to show the effectiveness of the proposed attitude coordinated tracking algorithms.

Thyme essential oil (TEO) and sausage diameter effects on biogenic amines (BA) formation and microbial communities in traditional Xinjiang smoked horse meat sausage were studied. Evaluation of the pH, moisture content, and microorganisms population of smoked horsemeat sausage was done. Significant differences due to sausage size were found for BA and microbial populations. Smaller diameter sausages showed decreased (P < 0.05) BA compared to the larger diameter sausages. The use of TEO greatly reduced BA (tyramine, putrescine, cadaverine, and histamine). In addition, TEO decreased the total bacterial count and more specifically the Gram-negative Enterobacteriaceaefamily (P < 0.05). High throughput sequencing showed that essential oil (EO) treatment and the difference in sausage diameter did not change the predominant microbiota in sausages during fermentation. However, the relative abundance of the microbiota can be changed. The correlation heat map showed relationships between the microbial community and BA production. Staphylococcus, Leuconostoc,and Lactobacillusshowed a strong positive relationship with BA formation.

Both ferroelectric crystals and liquid metal electrodes have attracted extensive attention for potential applications in next-generation devices and circuits. However, the interface information between ferroelectric crystals and liquid metal electrodes has so far been lacking. To better understand the optoelectronic properties of microscale ferroelectric crystals (potassium tantalate niobate, KTN) and its potential integration with liquid metal electrodes (a “printing ink” for flexible electric circuit production), microscale KTN crystals sandwiched by eutectic gallium indium (EGaIn, a liquid metal) with varied contact geometries were studied. Unlike the bulk KTN crystal junctions, the microscale KTN junctions show electrical rectifying characteristics upon light illumination, and the directionality of the rectification can be reversed by increasing the ambient temperature to a few degrees. Furthermore, a strong suppression of the current upon increasing voltage, that is, the quasi-negative differential resistance, is observed when the microscale KTN is half-enclosed by the EGaIn electrode. Our results show that trapping/detrapping of carriers affected by the crystal size and the ambient temperature is the dominant physical mechanism for these observations. These results not only facilitate a better understanding of charge transport through the microscale ferroelectric crystals but also advance the design of miniaturized hybrid devices.

ILD0 CMP and Al CMP plays important roles to form high k metal gate in the gate last approach for 32nm technology and beyond. It requires very tight control for the gate height and the surface topography. The gate height uniformity improvement, the dishing/erosion reduction and defect reduction are the key aspects for ILD0 CMP and Al CMP process development. Firstly, the polishing strategies and slurry selection are the most critical part. Several types of SiN slurries for ILD0 CMP process are evaluated. The impacts of SiN slurry's selectivity on dishing and poly thickness control are studied. The pros and cons of different CMP techniques, such as fixed abrasive CMP and slurry CMP for ILD0 CMP will be elaborated as well. Secondly, the pattern design and the design rules have significant impact on gate CMP process performance. The gate height and topography performance for different feature sizes and pattern densities are described and the dummy rule setup strategies are explored in this paper. Next, defect (Al pitts, scratches, particles, residues and as such) is another major challenge to a successful gate CMP process. The mechanism for the formation of the various types of defects is discussed and approaches for defect reduction are explored. In addition, the interation among the STI CMP, ILD0 CMP and Al CMP processes is discussed. Lastly, various process control and gate height monitor methods are compared and discussed in this paper.