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Due to higher mechanical strength and ultra-thin thickness, graphene is used as a sensitive diaphragm in a Fabry-Perot cavity to improve the sensitivity of pressure sensors. In accordance with the working principle of Fabry-Perot interferometer, a load-deflection mathematical model of fiber-tip pressure sensor with graphene membrane is established based on the large deflection elastic theory of circular membrane. The effects of membrane parameters, including prestressing force and membrane layer number, on deflection mechanical behaviors are studied by using finite element method. Also, the effects of graphene membrane layer and incident light angle on the film reflectivity are obtained according to the refractive index characteristics of the membrane. The simulation results show that an approximate linear relation between loads and deflections exists in the simulated pressure range from 0 to 3.5 kPa, and a theoretical pressure sensitivity of 1,096 nm/kPa for a single-layered graphene membrane can be achieved. To estimate the performance of multi-layered graphene membrane as the diaphragm, an extremely thin 13-layered 125-μm diameter graphene diaphragm is fabricated on the tip of the fiber end, which forms a low finesse Fabry-Perot interferometer. The Fabry-Perot cavity with a length of 40 μm can exhibit a fringe visibility of approximate 0.56 with a measured membrane reflectivity of 1.49 %. The experimental results demonstrate that the use of graphene as diaphragm material would allow highly sensitive and miniature fiber-tip sensors. [ABSTRACT FROM AUTHOR]

Bacteria living in marine sediment play crucial roles in the benthic-pelagic interface coupling process. However, the complexity of the marine environment and the abundance of interfering materials hamper metaproteomic research of the marine mudflat environment. In this study, a modified sequential protein extraction method was used for marine mudflat sediment metaproteomic investigation. For marine sediment samples in cultured clam mudflat, more than 1000 protein spots were visualized in a two-dimensional gel electrophoresis map and 78 % of 194 randomly selected spots were successfully identified by mass spectrometry. We further applied this method to compare long-term clam aquaculture and natural mudflat sediment and identified 53 altered proteins from different microbe resources, which belonged to different functional categories or metabolic pathways. We found that proteins involved in stress/defense response process, ATP regeneration and protein folding more inclined to increase abundance while arginine biosynthesis and signal transduction process related proteins preferred to decrease in clam cultured mudflat sediment. Meanwhile, proteins were abundant in pathogens of bivalves, such as Vibrio and Photobacterium, and decreased in Acinetobacter, after about 8 months clam cultured. Furthermore, the terminal restriction fragment length polymorphism assay was performed to compare microbial community composition between sediments mentioned above. Results showed that the top three enrich genera in natural sediment were Cytophaga, Butyrivibrio and Spirochaeta, while Cytophaga, Spirochaeta and Azoarcus were found enrichment in long-term mudflat aquaculture sediment. [ABSTRACT FROM AUTHOR]

The trade-off between high-temperature strength and room-temperature ductility represents a critical concern for practical application of refractory high-entropy alloys (RHEAs). Here, a set of five Re 0.1 Hf x Ta 1.6 W 0.4 (TaC) y refractory medium-entropy alloys (RMEAs) were fabricated using the vacuum arc melting technique, and the effect of Hf and C on the microstructures and mechanical properties of these alloys was investigated. These RMEAs exhibit excellent high-temperature strength and favorable plasticity at room-temperature. The microstructures of the Re 0.1 Hf x Ta 1.6 W 0.4 (TaC) y alloys are hypoeutectic or eutectic structures, consisting of BCC solid solution and primary and secondary carbides. The carbides can be classified into two types: M 2 C and MC. Hf and C have an important influence on the grain size, carbide type and spatial configuration of the alloy, and in turn, influence the mechanical properties of the alloy. For instance, the content of MC-type carbides is proportional to the addition of Hf element, whereby a higher proportion of Hf results in reduced plasticity at room-temperature and enhanced softening resistance at elevated temperatures in the alloy. The carbides and BCC matrix exhibit synergistic strengthening behavior. The ultimate compressive strength of the five Re 0.1 Hf x Ta 1.6 W 0.4 (TaC) y alloys at 1450 °C is >950 MPa, while maintaining a fracture strain exceeding 11% at room-temperature. Notably, the Re 0.1 Hf 0.1 Ta 1.6 W 0.4 (TaC) 0.25 alloy demonstrates a compressive strength of 1110 MPa at 1450 °C, which is 2.3 times greater than that of the NbMoTaW alloy at 1400 °C. Additionally, the fracture strain of the Re 0.1 Hf 0.1 Ta 1.6 W 0.4 (TaC) 0.25 alloy at room-temperature is 16.9%, which is 8 times higher than that of the NbMoTaW alloy. The Re 0.1 Hf x Ta 1.6 W 0.4 (TaC) y alloy exhibit excellent mechanical properties at both room and high temperatures, making it a potential candidate for applications in fields that require high strength at ultra-high temperatures. [Display omitted] • Re 0.1 Hf x Ta 1.6 W 0.4 (TaC) y alloys exhibit outstanding strength above 750 MPa at 1450 °C. • Re 0.1 Hf 0.1 Ta 1.6 W 0.4 (TaC) 0.25 alloy shows decent ductility at room-temperature. • The strength of different alloys can be described by the different carbide types. • The strengthening effect of carbide can be significantly influenced by Hf. [ABSTRACT FROM AUTHOR]

Binding of bile salts (BS) and protein has been linked to cholesterol reduction. However, the interaction between the protein structural and binding of BS ability was unclear. The goals of this study were to investigate the relationship among the structure, morphology, and functional properties of hydrolytic peptides of whey protein isolate (WPI) for four groups: control (no treatment), malic acid acidolysis [WPI + MA(DL)], enzymolysis (WPI-E), and enzymolysis combined with MA acidolysis [WPI-E+MA(DL)]. We found that the combination of enzymolysis and acidolysis could significantly improve the bile salt-binding ability of WPI (p < 0.05) by changing the structure and morphology of the protein compared with that in the other groups. An increase in the degree of hydrolysis, reduction in sulfhydryl group content, and exposure of aromatic amino acids indicated that WPI bound to the bile salts through hydrogen bond interactions. Additionally, the increase in surface hydrophobicity and β-sheet, β-turn, and random structure contents according to Fourier transform infrared spectroscopy indicated an exposure of hydrophobic groups. This further confirmed that WPI exhibited higher bile salt-binding ability through hydrophobic interactions. Sodium dodecyl sulphate-polyacrylamide gel electrophoresi (SDS-PAGE), Tricine-SDS-PAGE, scanning electron microscopy, and particle size analysis revealed that the hydrophobic groups exposed to the protein surface were aggregated and formed fragmented polymers with a molecular weight of approximately 3.3 kDa. Moreover, differential scanning calorimetry and rheology revealed that these polymers exhibited higher thermal stability, apparent viscosity, and viscoelasticity, and the viscosity was positively correlated with binding ability. Thus, the relationship between the structure, morphology and functional characteristics of hydrolytic peptides in the study can provide good data for designing innovative new peptides that ameliorate cholesterol and lipid metabolism. And it has good application value for the development of healthy and functional food. [Display omitted] • Structure–activity relationship were studied for cholesterol-lowering by malic acid combined enzymolysis (WPI-E+MA(DL)). • Higher bile salt binding capacity was found by WPI-E+MA(DL) treatment. • WPI-E+MA(DL) treatment showed obvious changes in the secondary and tertiary structures of protein. • WPI-E+MA(DL) treatment enhanced the surface hydrophobicity, thermal stability, apparent viscosity and viscoelasticity. • Fragmented polymers of 3.3 kDa were aggregated and formed with WPI-E+MA(DL) treatment. [ABSTRACT FROM AUTHOR]

Excessive protein and lipid oxidation can lead to the deterioration of sausage quality, especially flavour. Functional starter culture increases their attractiveness through sensory qualities and a potential healthpromoting effect. It was investigated that Lactobacillus plantarum (L.plantarum) strains with antioxidation properties effected on the flavour and oxidation of fermented sausage in the study. The group treated with natural fermentation was used to as control (control group). Results showed that P3 and P3-M2 had the ability of reducing lipid and protein oxidation during fermentation. The increase of lipoxygenase activity and thiobarbituric acid reactive substances (TBARs) values were retarded. Sulfhydryl group contents were significantly higher than those in the control. Furthermore, changes in protein bands were confirmed with the less protein oxidation with P3-M2 than P3 and the control. Accordingly, strain P3 and P3-M2 significantly enhanced the types and relative contents of esters after fermented, indicating that strain P3 and P3-M2 contributed to the production of flavour substances. These results revealed that L.plantarum strains with antioxidation properties were a promising approach in inhibiting lipid and protein oxidation of Chinese sausage, maintaining the stable natural structure of protein, simultaneously improve the quality of sausage and promote the sausage to form a better flavour. • L.plantarum strains are effective approachs in inhibiting lipid oxidation. • L.plantarum strains can promote a better flavor by enhancing esters. • L.plantarum strains are nature, safty and promising antioxdant in Chinese sausgae. [ABSTRACT FROM AUTHOR]

Summary: Single amino acid substitution (SAAS) produces the most common variant of protein function change under physiological conditions. As the number of SAAS events in plants has increased exponentially, an effective prediction tool is required to help identify and distinguish functional SAASs from the whole genome as either potentially causal traits or as variants. Here, we constructed a plant SAAS database that stores 12 865 SAASs in 6172 proteins and developed a tool called Plant Protein Variation Effect Detector (PPVED) that predicts the effect of SAASs on protein function in plants. PPVED achieved an 87% predictive accuracy when applied to plant SAASs, an accuracy that was much higher than those from six human database software: SIFT, PROVEAN, PANTHER‐PSEP, PhD‐SNP, PolyPhen‐2, and MutPred2. The predictive effect of six SAASs from three proteins in Arabidopsis and maize was validated with wet lab experiments, of which five substitution sites were accurately predicted. PPVED could facilitate the identification and characterization of genetic variants that explain observed phenotype variations in plants, contributing to solutions for challenges in functional genomics and systems biology. PPVED can be accessed under a CC‐BY (4.0) license via http://www.ppved.org.cn. [ABSTRACT FROM AUTHOR]

Pseudorabies virus (PRV) is an alpha herpesvirus that causes pseudorabies. After 2011, new and more pathogenic PRV variants have caused huge economic losses to the pig industry. In addition, people have been reported to be infected with PRV. Therefore, developing new anti-PRV drugs is of great significance. In this study, we investigated the anti-PRV activity of Hippophae rhamnoides polysaccharides (HRP) in vitro. We found that HRP could significantly inhibit the infectivity of the PRV XJ5 strain in PK15 cells. Addition of HRP at different times of the virus life cycle mainly led to the inhibition of the adsorption and entry of virus into the cells. Our results revealed that HRP can reduce the malondialdehyde (MDA) content and reactive oxygen species (ROS) level in PRV-infected PK15 cells and increase the superoxide dismutase (SOD) activity. These results suggested that HRP can reduce PRV infection-induced oxidative stress. Therefore, HRP may act as an antiviral drug against newly emerging PRV variants. [ABSTRACT FROM AUTHOR]

Considering the potential application of graphene in optical fibre Fabry-Perot pressure-sensitive membrane, a constitutive model for strain-induced deformation characteristics of graphene membrane was established based on the large deflection elastic theory of circular membrane. The effects of membrane parameters, including pre-stressing force, Young's modulus and membrane layer number on deflection mechanical behaviours were studied by using finite element method. The simulation results demonstrated that the pre-stressing force had a significant impact on the deflection deformation and natural frequency with small loads. And the values of Young's modulus should also be considered with large applied loads, because of the imperfect high-quality and uniform graphene preparation methods. Then we carried out a computational study of the effects of membrane thickness on its reflectivity with Fresnel's equations. It was shown that a single-layered graphene membrane with 25 μm diameter can achieve an approximate sensitivity of 80 nm/kPa for a 40 μm Fabry-Perot cavity. [ABSTRACT FROM AUTHOR]

We present a fishbone-like lumped-element artificial transmission line to overcome impedance mismatch in a reflection-type Josephson parametric amplifier between a nonlinear resonator and an external transmission line. Using this easily prepared architecture, we design and fabricate a broadband Josephson parametric amplifier, which has gain in an excess of 20 dB with a bandwidth of hundreds of MHz. Furthermore, by varying the working point of the device, the operating frequency of amplification can be tuned in a wide frequency range of 1 GHz while the amplifier operates in the mode of either three-wave mixing or four-wave mixing. Such a parametric amplifier is suitable for engineering applications of superconducting circuit quantum electrodynamics. [ABSTRACT FROM AUTHOR]

Feature selection in classification is an important task in machine learning. Inspired by the success of Universum support vector machine proposed by Weston et al. on improving the classification ability of classical support vector machine, this paper considers a special type of Universum and further lets it play its role in both useful feature identification and separating hyperplane construction, aiming to improve both the feature selection ability and classification performance of Universum support vector machine. By introducing this special Universum, a redundant feature can be identified by observing whether some Universum sample is useful. In fact, we prove that by observing the dual solution of the optimization problem, useful features can be selected from a set satisfying some properties. Due to the introduction of these extra Universum samples, it needs to cope with a large-scale optimization problem. To improve the training efficiency, we modify the sequential minimal optimization algorithm and further combine it with the coordinate descent technique to solve the proposed model. Experimental results on artificial datasets, benchmark datasets, and text classification datasets demonstrate that the proposed method improves the classification performance of support vector machine and Universum support vector machine, and also has good feature selection ability. • Special Universum samples are introduced to fulfill both feature selection and classification. • It identifies a feature as useful if its corresponding Universum sample contributes to classification. • An effective algorithm by combining modified SMO and coordinate descent technique is designed. [ABSTRACT FROM AUTHOR]

[Display omitted] • 17 undescribed 3a, 9b-furan-type terpenylated coumarins were isolated. • The absolute configuration of terpenylated coumarins 1 – 25 was identified firstly. • Anti-neuroinflammatory effects of 3a, 9b-furan-type terpenylated coumarin revealed firstly. • Ferulaferone B can be considered as a promising anti-neuroinflammatory structure and may worth further development. A total of 37 characteristic terpenylated coumarins (1 – 25), including 17 undescribed compounds (1 – 5, 6a/6b, 7 – 10, 11a / 11b – 13a / 13b), have been isolated from the root of Ferula ferulaeoides. Meanwhile, twelve pairs of enantiomers (6a / 6b , 11a / 11b – 15a / 15b, 17a / 17b, 18a / 18b, 20a / 20b – 22a / 22b, and 25a / 25b) were chirally purified. The structures of these new compounds were elucidated using HRESIMS, UV, NMR, and calculated 13C NMR with a custom DP4 + analysis. The absolute configurations of all the compounds were determined for the first time using electronic circular dichroism (ECD). Then, their inhibitory effects on nitric oxide (NO) production were evaluated with LPS-induced BV-2 microglia. Compared with the positive control minocycline (IC 50 = 59.3 μM), ferulaferone B (2) exhibited stronger inhibitory potency with an IC 50 value of 12.4 μM. The immunofluorescence investigation indicated that ferulaferone B (2) could inhibit Iba-1 expression in LPS-stimulated BV-2 microglia. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, the dynamic response characteristics of ceramic targets impacted by a long tungsten projectile at a high speed are investigated through an improved theoretical model. The model, based on conventional quasi-static cavity expansion theory, takes the effect of the target damage caused by penetration on the constitutive equation into account. A few useful relations of the target resistance and the penetration velocity are derived from the model and the stationary incompressible hydrodynamic theory. In order to examine the dynamic damage response of alumina ceramics to projectile impact and the theoretical model, we set up the experimental system of a high-speed, long tungsten projectile with its sabot separation device penetrating ceramic targets with/without cover plate, carried out a series of penetration experiments, and compared the experimental results with theoretical calculation and numerical simulation results. Theoretical and experimental results show that 1) the anti-penetration ability of AD90 ceramic is higher than that of 45# steel, especially, in the low-speed stage of the projectile; 2) material parameters of AD90 ceramic obtained from the numerical simulation of projectile penetration are reasonable; 3) the cover plate covered on the front of the ceramic target can improve the anti-penetration ability, while the constraint sleeve enclosed the ceramic target has little effect on the anti-penetration ability; 4) from the numerical simulations, the damage caused by penetration in the target with the cover plate is initiated by the tensile wave reflected from the back of ceramic, while the damage in the non-plate target is initiated by direct impact, and then develops at the target back by tensile wave; and 5) the theoretical model presented in this paper is proven to be reasonable, can be used to further studying on dynamic response of target materials under penetration. [Copyright &y& Elsevier]

Hair follicle development and wool shedding in sheep are poorly understood. This study investigated the population structures and genetic differences between sheep with different wool types to identify candidate genes related to these traits. We used Illumina ovine SNP 50K chip genotyping data of 795 sheep populations comprising 27 breeds with two wool types, measuring the population differentiation index (Fst), nucleotide diversity (θπ ratio), and extended haplotype homozygosity among populations (XP-EHH) to detect the selective signatures of hair sheep and fine-wool sheep. The top 5% of the Fst and θπ ratio values, and values of XP-EHH < −2 were considered strongly selected SNP sites. Annotation showed that the PRX, SOX18, TGM3, and TCF3 genes related to hair follicle development and wool shedding were strongly selected. Our results indicated that these methods identified important genes related to hair follicle formation, epidermal differentiation, and hair follicle stem cell development, and provide a meaningful reference for further study on the molecular mechanisms of economically important traits in sheep. [ABSTRACT FROM AUTHOR]

Smoking cessation increases body weight. The underlying mechanisms, however, have not been fully understood. We here report an establishment of a mouse model that exhibits an augmented body weight gain after nicotine withdrawal. High fat diet-fed mice were infused with nicotine for two weeks, and then with vehicle for another two weeks using osmotic minipumps. Body weight increased immediately after nicotine cessation and was significantly higher than that of mice continued on nicotine. Mice switched to vehicle consumed more food than nicotine-continued mice during the first week of cessation, while oxygen consumption was comparable. Elevated expression of orexigenic agouti-related peptide was observed in the hypothalamic appetite center. Pair-feeding experiment revealed that the accelerated weight gain after nicotine withdrawal is explained by enhanced energy intake. As a showcase of an efficacy of pharmacologic intervention, exendin-4 was administered and showed a potent suppression of energy intake and weight gain in mice withdrawn from nicotine. Our current model provides a unique platform for the investigation of the changes of energy regulation after smoking cessation. • Smoking cessation is accompanied by increased body weight. • A mouse model of weight gain after nicotine withdrawal is established. • Food intake and orexigenic peptide expression are enhanced immediately after nicotine withdrawal. • Dependence of body weight gain on increased food intake is shown by pair-feeding experiment. • Exendin-4, a glucagon-like peptide-1 analog, proves to be an effective therapy. [ABSTRACT FROM AUTHOR]

Background: Exosomes secreted from stem cells exerted salutary effects on the fibrotic liver. Herein, the roles of exosomes derived from human embryonic stem cell (hESC) in anti-fibrosis were extensively investigated. Compared with two-dimensional (2D) culture, the clinical and biological relevance of three-dimensional (3D) cell spheroids were greater because of their higher regeneration potential since they behave more like cells in vivo. In our study, exosomes derived from 3D human embryonic stem cells (hESC) spheroids and the monolayer (2D) hESCs were collected and compared the therapeutic potential for fibrotic liver in vitro and in vivo. Results: In vitro, PKH26 labeled-hESC-Exosomes were shown to be internalized and integrated into TGFβ-activated-LX2 cells, and reduced the expression of profibrogenic markers, thereby regulating cellular phenotypes. TPEF imaging indicated that PKH26-labeled-3D-hESC-Exsomes possessed an enhanced capacity to accumulate in the livers and exhibited more dramatic therapeutic potential in the injured livers of fibrosis mouse model. 3D-hESC-Exosomes decreased profibrogenic markers and liver injury markers, and improved the level of liver functioning proteins, eventually restoring liver function of fibrosis mice. miRNA array revealed a significant enrichment of miR-6766-3p in 3D-hESC-Exosomes, moreover, bioinformatics and dual luciferase reporter assay identified and confirmed the TGFβRII gene as the target of miR-6766-3p. Furthermore, the delivery of miR-6766-3p into activated-LX2 cells decreased cell proliferation, chemotaxis and profibrotic effects, and further investigation demonstrated that the expression of target gene TGFβRII and its downstream SMADs proteins, especially phosphorylated protein p-SMAD2/3 was also notably down-regulated by miR-6766-3p. These findings unveiled that miR-6766-3p in 3D-hESC-Exosomes inactivated SMADs signaling by inhibiting TGFβRII expression, consequently attenuating stellate cell activation and suppressing liver fibrosis. Conclusions: Our results showed that miR-6766-3p in the 3D-hESC-Exosomes inactivates smads signaling by restraining TGFβRII expression, attenuated LX2 cell activation and suppressed liver fibrosis, suggesting that 3D-hESC-Exosome enriched-miR-6766-3p is a novel anti-fibrotic therapeutics for treating chronic liver disease. These results also proposed a significant strategy that 3D-Exo could be used as natural nanoparticles to rescue liver injury via delivering antifibrotic miR-6766-3p. [ABSTRACT FROM AUTHOR]

Abstract: Many source waters in China are in high levels of natural organic matter (NOM) and bromide ion (Br−), and the control of the formation of regulated and non-regulated disinfection by-products (DBPs) is a great challenge. This study uses the natural water with substantial NOM and Br− from Weishan Lake to evaluate the formation and species transformation of DBPs in three disinfection scenarios of chlorination, chloramination, and chlorine–chloramine sequential treatment (Cl2–NH2Cl process), and the reaction pathways involved are also proposed. Compared with chlorination, the formation of trihalomethanes and haloacetic acids is reduced by 88% and 85% and by 68% and 65% in chloramination and Cl2–NH2Cl process, respectively. During chloramination, the proportion of brominated-DBPs (Br-DBPs) is lower initially, and then increases afterwards due to the continuous reaction between NOM slow reactive sites and N-bromo amines. Additionally, the ratios of dihalogenated acetic acids to total organic halogen increase continuously from 4.5% to 6.3% with pre-chlorination and from 4.3% to 9.8% without pre-chlorination. The halonitriles (HANs) formation during chlorination is the most significant in the initial 30min at the level of 6.5nM, and then decreases to 2.5nM after 72h. During chloramination, however, the formation of HANs increases steadily with prolonged contact time. After 72-h contact time, the level of HANs in Cl2–NH2Cl process is 3.9 and 2.5 times of that in chlorination and chloramination, respectively. In Cl2–NH2Cl process, HOCl rapidly oxidizes Br− to HOBr, and these two active species react with the fast reactive sites within NOM to form Br-DBPs and the intermediates for nitrogenous DBPs (N-DBPs). The subsequent introduction of ammonia inhibits the hydrolysis and oxidation of the formed N-DBPs and contributes to the most significant formation of N-DBPs. [Copyright &y& Elsevier]

Abstract: In this paper, we reported the synthesis of well dispersed Pd nanoparticles (PdNPs)-decorated poly(o-phenylenediamine) (PoPD) colloids without any surfactants. The PoPD colloids were easily prepared via chemical polymerization of oPD monomers by ammonium persulfate (APS) at room temperature. The nano-sized and well-dispersed PdNPs on PoPD could be obtained through an effective two step chemical reduction route. First, the nitrogen atoms on the surface of PoPD could coordinate to ions, and PoPD was oxidized with simultaneous reduction of a part of Pd2+ to Pd0 (the sample was denoted as Pd/P1). Thereby, PdNPs could be anchored and stabilized by the amino group of PoPD. In the second step, with the addition of the ascorbic acid, the Pd/P1 was further transformed into Pd/P2 because of strong reduction of ascorbic acid. A large amount of excellent dispersed PdNPs with tens of nanometer size were supported on PoPD colloids. Notably, the Pd/P2 catalyst exhibited excellent catalytic activity towards hydrazine electrooxidation. It should be contributed to changed mass transport and the existence of porosity. This provides a promising approach to prepare polymer-based nanoelectrocatalysts with high performance for hydrazine oxidation. [Copyright &y& Elsevier]

Abstract: The high-yield crystalline silver nanoplates were synthesized by mixing para-phenylenediamine (PPD) and silver nitrate with the addition of an appropriate amount of formic acid at low temperature. X-ray diffraction measurements show that the silver samples are pure face-centered cubic (fcc) phase with a preferred orientation of (111) direction. The silver nanoplates modified electrode (AgNP/GC) exhibits an excellent electrocatalytic activity toward the oxidation of nitrite . The corresponding linear range and detection limit are estimated to be from 1×10−5 M to 1×10−3 M (r =0.999) and 1.2×10−6 M, respectively, at a signal-to-noise ratio of 3. It was successfully applied to the determination of nitrite in some food samples and the results were consistent with those obtained with the standard spectrometer procedure. [Copyright &y& Elsevier]

Abstract: The complete genomic sequence of Lactobacillus fermentum temperate bacteriophage ФPYB5 was determined. The phage possesses a linear, double-stranded DNA genome of 32,847bp with a G+C content of 45.21%. A total of 46 putative open reading frames (ORFs) were identified. On the basis of homology comparisons, 25 ORFs could be assigned putative functions. The genome of bacteriophage ФPYB5 is highly modular with functionally related genes clustered together. Genome DNA of temperate bacteriophage ФPYB5, induced from heterofermentative lactic acid bacteria, showed to be closely related to that of the prophage of heterofermentative Lactobacillus reuteri 100-23 and heterofermetative Leuconostoc oenos bacteriophage 10MC in an evolutionary aspect. [ABSTRACT FROM AUTHOR]

Abstract: A rapid, sensitive and simple high performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) method was developed for determination of cefazedone in human plasma using metronidazole as internal standard (IS). The chromatographic separation was achieved on an Ultimate XB-CN column (2.1mm×150mm, 5μm) with an isocratic mobile phase of acetonitrile and 20mM ammonium acetate in 0.1% formic acid in water (15:85, v/v). Detection was performed using electrospray ionization in positive ion multiple reaction-monitoring mode (SRM), monitoring the transitions m/z 548.2→344.1 for cefazedone and m/z 172.2→128.1 for IS. Calibration curves were linear over a wide range of 0.20–401.12μg/mL for cefazedone in plasma. The lower limit of quantification (LLOQ) was 0.20μg/mL. The intra- and inter-day precisions were less than 7.2%. The average recovery of cefazedone was 90.8–91.0%. The validated method was successfully applied to the pharmacokinetic study of cefazedone in Chinese healthy volunteers following intravenous (IV) administration of 500, 1000 and 2000mg cefazedone injection. [ABSTRACT FROM AUTHOR]

Microtubules are essential components of the cytoskeleton that participate in a variety of cellular processes such as cell division and migration. In addition, there is a growing body of evidence implicating a role for microtubules in intracellular viral transport. In this study, we found that pharmacological disruption of microtubules remarkably blocked bovine immunodeficiency virus (BIV) movement from the cell periphery to the perinuclear region, a process known as retrograde transport. A similar effect was observed by inhibiting function of the microtubule-associated motor protein dynein. By yeast two-hybrid assay, we found that the capsid protein (CA) of BIV interacted with the dynein light-chain component LC8. Immunoprecipitation and GST-pulldown assays further demonstrated an interaction between CA and LC8 in mammalian cells. In addition, our data revealed LC8 as a linker between BIV particles and microtubules. Retrograde transport of BIV was significantly inhibited by knockdown of LC8 expression. Our findings present the first evidence that incoming BIV particles employ host microtubule/dynein machinery for transport towards the perinuclear region. In addition, our data indicate that the LC8–CA interaction is a potential target for the design of antiviral strategies. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Gan-kang granules (GKG) contains the extracts from eight Chinese herbs and is a traditional Chinese composite prescription for treatment of hepatitis B. Icariin, emodin and psoralen are main effective ingredients of the medicine. Aim of the study: In this research, pharmacokinetic comparisons of icariin, emodin and psoralen from the extracts of Herba Epimedii, Nepal dock root and Ficus hirta yahl, and GKG were conducted. Materials and methods: At different time points (0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12 and 24h) after administration, the concentrations of icariin, emodin and psoralen in rat plasma were determined by HPLC-UV, and main pharmacokinetic parameters were estimated. Results: The pharmacokinetic parameters of icariin, emodin and psoralen in GKG were elevated comparing with those of herb extracts. Conclusions: Three HPLC-UV methods were developed successfully for the analysis of icariin, emodin and psoralen in SD rat plasma. Some ingredients in GKG may increase the dissolution and absorption, and improve bioavailability of icariin, emodin and psoralen in rats. [Copyright &y& Elsevier]

The control of microstructure, texture and deformation inhomogeneity is critical for the hot working of titanium alloys and to optimize their mechanical properties. Herein, a new approach to control the grain refinement, texture and deformation anisotropy of commercial purity titanium (CP–Ti) was established through hot working of a martensitic starting microstructure. The deformation characteristics of the martensitic CP-Ti were investigated through uniaxial hot compression testing at 800 °C and compared with the same alloy with an equiaxed starting microstructure. The associated microstructure, texture development and grain refinement mechanisms were elucidated using electron backscatter diffraction (EBSD) and flow behavior analysis. The equiaxed microstructure displayed a typical flow behaviour of metals undergoing continuous dynamic recrystallization (CDRX). This was accompanied by moderate grain refinement to ∼8.2 μm and macroscopically non-uniform expansion of specimen. In comparison, the martensitic microstructure revealed a stress-strain curve of continuous softening beyond the peak strain. An enhanced grain refinement to ∼5 μm was obtained also via CDRX in the form of kinking of laths and progressive lattice rotation without noticeable macroscopic deformation anisotropy. This distinct deformation behaviour was mainly attributed to the unique microstructure and texture formed through the martensitic transformation, which altered the activation of slip systems, grain refinement kinetics and texture development during hot deformation. • The grain refinement of CP-Ti was remarkably enhanced by transforming the starting microstructure from equiaxed coarse grains into martensite prior to hot deformation at 800 °C. ii. A markedly weakened texture was developed in the deformed martensitic CP-Ti due to multiplication of α variant formation from a given β grain through the β.→α transformation, which also contributed to reduced deformation anisotropy. iii. The equiaxed and martensitic CP-Ti were both refined via continuous dynamic recrystallization while the martensitic Ti exhibited enhanced grain refinement mainly due to a refined lath thickness and randomized orientation, which enabled lath kinking and activation of slip during deformation. [ABSTRACT FROM AUTHOR]

We report de novo genome assemblies, transcriptomes, annotations, and methylomes for the 26 inbreds that serve as the founders for the maize nested association mapping population. The number of pan-genes in these diverse genomes exceeds 103,000, with approximately a third found across all genotypes. The results demonstrate that the ancient tetraploid character of maize continues to degrade by fractionation to the present day. Excellent contiguity over repeat arrays and complete annotation of centromeres revealed additional variation in major cytological landmarks. We show that combining structural variation with single-nucleotide polymorphisms can improve the power of quantitative mapping studies. We also document variation at the level of DNA methylation and demonstrate that unmethylated regions are enriched for cis-regulatory elements that contribute to phenotypic variation. [ABSTRACT FROM AUTHOR]

In this paper, a multilayer graphene mixer with inductor‐capacitor resonators (LCR) and microstrip reflector stubs (MRS) loaded with direct‐current (DC) voltage bias is presented. As a multifunctional material, multilayer graphene is especially suitable for mixer because of its nonlinearity. The experimental and simulation results show that the effect of bias voltage on multilayer graphene is significant. When the bias voltage is applied, the mixer is converted from subharmonic mixer to fundamental wave mixer. The measured minimum conversion loss with DC‐load fundamental wave mixer is 18.9 dB at PLO = 16 dBm, fLO = 800 MHz, pRF = 0 dBm, fRF = 2 GHz which is about 1.2 dB lower than that DC‐free subharmonic mixer. In addition, the nonlinear model of graphene is established by simplifying the approximate conductivity. [ABSTRACT FROM AUTHOR]

[Display omitted] Acute myeloid leukemia (AML) with FLT3 internal tandem duplication (FLT3 -ITD) has a dismal prognosis. FLT3 inhibitors have been developed to treat patients with FLT3 -ITD AML; however, when used alone, their efficacy is insufficient. FLT3 inhibitors combined with chemotherapy may be a promising treatment for FLT3 -ITD AML. Homoharringtonine (HHT) is a classical anti-leukaemia drug with high sensitivity to FLT3 -ITD AML cells. Here, we showed that HHT synergizes with a selective next-generation FLT3 inhibitor, quizartinib, to inhibit cell growth/viability and induce cell-cycle arrest and apoptosis in FLT3 -ITD AML cells in vitro, significantly inhibit acute myeloid leukemia progression in vivo, and substantially prolong survival of mice-bearing human FLT3 -ITD AML. Mechanistically, HHT and quizartinib cooperatively inhibit FLT3-AKT and its downstream targets GSK3β, c-Myc, and cyclin D1, cooperatively up-regulate the pro-apoptosis proteins Bim and Bax, and down-regulate the anti-apoptosis protein Mcl1. Most strikingly, HHT and quizartinib cooperatively reduce the numbers of side-population (SP) and aldehyde dehydrogenase (ALDH)-positive cells, which reportedly are rich in LSCs. In conclusion, HHT combined with quizartinib may be a promising treatment strategy for patients with FLT3 -ITD AML. [ABSTRACT FROM AUTHOR]

Lactic acid bacteria (LAB) are a phylogenetically diverse group with the ability to convert soluble carbohydrates into lactic acid. Many LAB have a long history of safe use in fermented foods and are recognized as food-grade microorganisms. LAB are also natural inhabitants of the human intestinal tract and have beneficial effects on health. Considering these properties, LAB have potential applications as biotherapeutic vehicles to delivery cytokines, antigens and other medicinal molecules. In this review, we summarize the development of, and advances in, genome manipulation techniques for engineering LAB and the expected future development of such genetic tools. These methods are crucial for us to maximize the value of LAB. We also discuss applications of the genome-editing tools in enhancing probiotic characteristics and therapeutic functionalities of LAB. [ABSTRACT FROM AUTHOR]

A multilayer graphene frequency doubler (GFD) with inductance–capacitor resonators (LCRs) and microstrip reflective stubs (MRS) is proposed in this paper. Graphene has strong nonlinear characteristics. Under the excitation of electromagnetic waves, the output power of odd harmonic of graphene is greater than that of even harmonic. Under the joint excitation of electromagnetic wave and bias voltage, the even harmonic output power of graphene is enhanced and the odd harmonic is suppressed, which is very suitable for making GFD. On the basis of analyzing the conductivity of graphene, the symbolically defined device model of multilayer graphene is established, and the model is applied to GFD circuit, the simulation results are basically consistent with the experimental data. The multiplier efficiency of graphene can be effectively improved by the bias voltage and LCR and the MRS. At an operating frequency of 0.65–1.15 GHz, the minimum conversion loss (CL) of the GFD is 20.57 dB when the input power is 16 dBm. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most common malignancies and causes poor outcome. Dysregulation of long noncoding RNA (lncRNA) is involved in HCC. Upregulation of the lncRNA PCNAP1 has been reported to promote HBV-infectious HCC growth, but its clinical significance and underlying mechanisms in HCC development remain unclear. Here, we report that PCNAP1 expression is increased in both HBV-infectious and noninfectious HCC tissues compared with matched normal tissues, and its upregulation correlates with poor survival rates of HCC patients. Furthermore, we found that PCNAP1 promotes HCC cell proliferation through acting as a competitive endogenous RNA (ceRNA) to sponge miR-340-5p, which has been reported to directly inhibit ATF7 expression in HCC cells. Moreover, the PCNAP1/miR-340-5p/ATF7 signaling associates with the poor survival rates of HCC patients. Collectively, our findings suggest that the PCNAP1/miR-340-5p/ATF7 signaling may be a potential biomarker for the prognosis of HCC patients and a potential therapeutic target for HCC. [ABSTRACT FROM AUTHOR]

The storage period of European pear (Pyrus communis L.) is prolonged at low temperature, but the pear softened quickly after shifting to room temperature. However, the molecular mechanisms that influence this process are unknown. In this study, 'Docteur Jules Guyot' pears were placed at room temperature (RT) and low temperature and then turned to room temperature (LR). The fruit firmness of 'Docteur Jules Guyot' under LR decreased faster than RT after moving from low temperature. The ethylene production rate, water-soluble pectin (WSP), ionic-soluble pectin (ISP) content, and pectin degradation enzyme activity of 'Docteur Jules Guyot' under LR increased faster than RT after moving from low temperature. RNA-seq of 'Docteur Jules Guyot' pear under different storage conditions was carried out, and 1018 genes were found to be negatively correlated with fruit firmness by the weighted gene coexpression network analysis (WGCNA) method. Then, 24 structural genes and transcription factors related to fruit softening were selected to verify the RNA-Seq results. The expression of all these selected genes increased significantly after LT storage. The fruit firmness, pectin content, and pectin degradation enzyme activity of 'Laiyang' pear did not change significantly under RT and LR storage conditions. The expression of LAX2 , ARF19 , EXP1 , EXPA1 , EXP3 and PG2 was upregulated in 'Docteur Jules Guyot' pear but downregulated in 'Laiyang' pear. These genes might play important roles in the softening process of European pear. This work laid the foundation for revealing the mechanisms of European pear fruit softening. • Low temperature accelerated the softening of 'Docteur Jules Guyot' pear after shifting to room temperature. • WGCNA identifies two key modules involved in pear fruit softening. • The expression trend of some genes in European and Asian pears was completely opposite. • LAX2 , ARF19 , EXP1 , EXPA1 , EXP3 and PG2 may play important roles in European pear softening. [ABSTRACT FROM AUTHOR]

The relationship between cognitive reappraisal's creativity (both novelty and appropriateness), positivity (the positive or negative attitudes), and emotion regulation efficacy was analyzed. Positivity was found to play a full mediating role between creativity and regulation effectiveness. [ABSTRACT FROM AUTHOR]

Although nanoporous shape-stabilized composite phase change materials (PCMs) could efficiently address the leakage issue of pure PCMs during the solid-liquid phase transition process, numerous experiments have verified that the thermophysical parameters of the nanoporous shape-stabilized composite PCMs are significantly different from those of macroscopic bulk PCMs due to the nanoconfinement effects. However, macroscopic experimental data cannot directly reflect the microscopic interaction mechanisms in composite PCMs. Herein, to systematically understand the molecular motion mechanisms of PCMs with different functional groups (octadecane, octadecylamine, octadecanol and stearic acid) confined in the mesoporous MCM-41, we utilize molecular dynamics to simulate the spatial distribution and motion states of surface adsorbed PCMs molecules. This study aims to systematically reveal the interaction mechanisms between mesoporous MCM-41 and surface adsorbed PCMs at the molecular and atomic levels, thus providing constructive theoretical guidance and reference data for the targeted design and preparation of high-performance MCM-41-based composite PCMs. Image 1 • Molecular dynamics method is utilized to study thermal motion states of PCMs in mesoporous MCM-41. • The interaction mechanisms between MCM-41 and PCMs are systematically revealed at the molecular level. • It provides constructive guidance for the preparation of MCM-41-based composite PCMs. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is the dominant cause of end-stage renal disease which is characterized by extracellular matrix accumulation. The purpose of this study was to investigate the role of activating transcription factor 4 (ATF4) in regulating renal fibrosis and autophagy in DN. Streptozotocin (STZ) was administered to heterozygous ATF4 knockout (KO) and wild-type (WT) mice via an intraperitoneal injection to induce DN. NRK-52E cells were cultured in high glucose to mimic diabetic pathological. qRT-PCR, western blot, immunofluorescence, histology and electron microscopic analysis were performed. The autophagy flux was observed by tandem mRFP-GFP-LC3 fluorescence microscopy. DN mice experienced severe renal injury and fibrosis and showed increased expression of ATF4 and inhibition of autophagy in kidney tissues. We found that STZ-induced ATF4 KO mice showed significant improvement in urinary albumin, serum creatinine and blood urea nitrogen and the pathological changes of renal tubulointerstitial fibrosis compared with STZ-induced WT mice. Furthermore, inhibition of ATF4 could restore autophagy in DN mice. Similar results were shown in vitro. Overexpression of ATF4 in NRK-52E cells cultured in high glucose condition suppressed autophagy and upregulated Collagen type 4 (Col-IV) expression, while inhibition of ATF4 could increase the number of the autophagosomes, improve autophagic flux and decrease Col-IV level. Our study provided the evidence of a crucial role for ATF4 in inhibiting autophagy against diabetic kidney damage. Suppression of ATF4 may be an effective therapy in restraining renal tubulointerstitial fibrosis in DN. [ABSTRACT FROM AUTHOR]

Designing van der Waals' heterostructures with prominent properties is crucial to improve the performance of nanoscale optoelectronic devices. In this article, the structural stability and electronic properties of Sb/AlAs heterostructures were investigated by comprehensive first-principles calculations. It is worth noting that Sb/AlAs heterostructures have good thermal stability and a small lattice mismatch. Owing to suitable direct-gap and intrinsic type-II band alignment, effective separation of photogenerated carriers occurs at the interface, which has numerous optoelectronic properties suitable for use in photodetectors. Furthermore, the heterostructure undergoes transition from indirect-gap to direct-gap under vertical strain. When an external electric field is applied, the charge transfer is significantly enhanced and a semiconductor–metal transition is accomplished. The biaxial strain can induce indirect–direct–indirect transition, and the effective mass of electrons and holes exhibit notable anisotropy, which can be modulated by tensile and compressive strain. The above-mentioned results provide valuable theoretical guidance for designing high-quality Sb-based heterostructures and specify an orientation for high-performance photodetector applications. [ABSTRACT FROM AUTHOR]

The present paper performs a two-dimensional numerical study of the interactions between {10 1 ¯ 2} tensile twin and precipitates aligned along basal planes in magnesium alloys. The model consists of an elliptical twin placed in between two rectangular precipitates. Material behavior is modeled using anisotropic elasticity and crystal plasticity. The model represents the situation at the onset of twinning when twins are small and fit in between the precipitates. The results show that precipitates influence the shear stress necessary to accommodate twin by changing the slip critical resolved shear stress (CRSS) values and by acting as obstacles. Thin twins (aspect ratio <0.05) are influenced by both effects while thick twins (aspect ratio >0.1) are influenced by slip CRSS changes. The precipitate thickness plays a crucial role in twin thickening and propagation. Increasing precipitate thickness increases shear stress necessary to accommodate twin and also decreases stress beyond the precipitate which hinders sequential twin propagation. Image, graphical abstract [ABSTRACT FROM AUTHOR]

This study aimed to elucidate the underlying mechanisms for the protective effect of Lactobacillus on hypercholesterolemia. Firstly, twenty Lactobacillus strains were screened for potential probiotics with high bile salt hydrolase (BSH) activity using in vitro methods. Secondly, hypercholesterolemic mice induced by a cholesterol-enriched diet were administrated by the probiotic candidate strain L. plantarum Y15, identified from the screen. Results in vitro showed that L. plantarum Y15 possessed high BSH activity. In vivo, L. plantarum Y15 supplementation decreased total cholesterol and triglyceride in serum and liver, increased total cholesterol and total bile acid in feces, and alleviated histopathological changes in the liver. Furthermore, L. plantarum Y15 supplementation modulated the gut microbiota to the control group's pattern, leading to increase BSH activity, which further influence FXR and SHP signaling pathway to upregulate the expression level of CYP7A1 to enhance the cholesterol catabolism. [ABSTRACT FROM AUTHOR]

Breast cancer stem cells are an important cause of radiotherapy resistance in the clinical treatment of breast cancer patients. How to target breast cancer stem cells is the key to improving the efficacy of breast cancer radiotherapy. We proposed for the first time that curcumin combined with glucose nanogold particles (Glu-GNPs) targeted breast cancer stem cells to reduce radiotherapy resistance, which can significantly enhance the apoptosis level of MCF-7 and MDA-MB-231 breast cancer stem-like cells (BCSCs) after radiotherapy and antiproliferation and colony-forming. Under simulated hypoxic conditions, curcumin combined with Glu-GNPs can significantly improve the ROS level of MCF-7 and MDA-MB-231 mammospheres; reduce the expression of HIF-1α and HSP90, thereby inhibiting the tumor cells' own stress ability; promote the apoptosis of tumor stem cells; and enhance the sensitivity of radiotherapy. The current results indicate that the combination of curcumin and Glu-GNPs has great potential to relieve tumor hypoxia and increase radiosensitivity on BCSCs, providing scientific research data for developing a novel radiosensitizer with high efficiency and low toxicity. [ABSTRACT FROM AUTHOR]

Summary: Effective evaluation of millions of crop genetic stocks is an essential component of exploiting genetic diversity to achieve global food security. By leveraging genomics and data analytics, genomic prediction is a promising strategy to efficiently explore the potential of these gene banks by starting with phenotyping a small designed subset. Reliable genomic predictions have enhanced selection of many macroscopic phenotypes in plants and animals. However, the use of genomicprediction strategies for analysis of microscopic phenotypes is limited. Here, we exploited the power of genomic prediction for eight maize traits related to the shoot apical meristem (SAM), the microscopic stem cell niche that generates all the above‐ground organs of the plant. With 435 713 genomewide single‐nucleotide polymorphisms (SNPs), we predicted SAM morphology traits for 2687 diverse maize inbreds based on a model trained from 369 inbreds. An empirical validation experiment with 488 inbreds obtained a prediction accuracy of 0.37–0.57 across eight traits. In addition, we show that a significantly higher prediction accuracy was achieved by leveraging the U value (upper bound for reliability) that quantifies the genomic relationships of the validation set with the training set. Our findings suggest that double selection considering both prediction and reliability can be implemented in choosing selection candidates for phenotyping when exploring new diversity is desired. In this case, individuals with less extreme predicted values and moderate reliability values can be considered. Our study expands the turbocharging gene banks via genomic prediction from the macrophenotypes into the microphenotypic space. [ABSTRACT FROM AUTHOR]

No-tillage (UT) and tillage (TL) influence melon (Cucumis melo L.) production. However, the mechanism of improving the soil quality under UT in melon production is still unavailable. In this study, we attempted to explore the effects of UT and TL treatments on soil fertility and the microbial abundance and diversity in planting melon under greenhouse condition. Soil properties were determined and the bacterial v4-v5 16S rRNA and the fungal internal transcribed spacer gene were pyrosequenced by extracting greenhouse soil DNA. Results showed that the two treatments had different effects on nutrient uptake in melon plants under facility conditions. Additional nitrogen (N) was absorbed in the leaves and fruit in UT treatment. However, the N content in the UT treatment was kept as similar to that of the TL treatment. The phosphorus (P) contents in melon plant leaves and fruits in the UT treatment were higher than those in the TL treatment. High potassium (K) contents were observed in fruits and melon stem under the UT and TL treatments, respectively. Soil pH, organic matter and the available N influenced the bacterial and fungal distributions. The total N, total P and total K in melon plants were correlated with the bacterial and fungal groups in facility soils. The UT treatment had a substantial effect on the microbial diversity in soils planted with melon. Our study provided insights into the response of soil fertility and microbial structures to UT and TL treatments under greenhouse soils, which may aid in managing greenhouse soil quality. [ABSTRACT FROM AUTHOR]

The efficacy and safety of ticagrelor and clopidogrel in East Asian patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) remains uncertain. The purpose of this study was to compare the efficacy and safety of ticagrelor and clopidogrel in East Asian patients with CAD treated with PCI. A total of 12383 patients with CAD undergoing PCI who received dual antiplatelet therapy (DAPT) were consecutively enrolled in the ticagrelor group (n = 1321) and the clopidogrel group (n = 11062). Major adverse cardiovascular and cerebrovascular events (MACCEs) and thrombolysis in myocardial infarction (TIMI) bleeding events were compared according to ticagrelor or clopidogrel use were compared. After propensity matching (n = 1321 in each group), ticagrelor was associated with lower incidence of MACCEs compared with clopidogrel (3.9 vs. 5.9%, hazard ratio [HR] = 0.65, 95% confidence interval [CI] 0.45–0.92, p =.015). The incidence of TIMI bleeding events was higher in the ticagrelor group than in the clopidogrel group (4.5 vs. 2.9%, HR = 1.90, 95% CI 1.25–2.88, p =.024). The difference between ticagrelor and clopidogrel for net adverse clinical events was nonsignificant (4.3 vs. 4.9%, HR = 0.88, 95% CI 0.61–1.27, p =.458). Ticagrelor was associated with a lower incidence of MACCEs and an increased risk of TIMI bleeding events in East Asian patients with CAD receiving PCI. [ABSTRACT FROM AUTHOR]

Most sheep breeding programs designed for the tropics and sub-tropics have to take into account the impacts of environmental adaptive traits. However, the genetic mechanism regulating the multiple biological processes driving adaptive responses remains unclear. In this study, we applied a selective sweep analysis by combing 1% top values of Fst and ZHp on both altitude and geographic subpopulations (APS) in 636 indigenous Tibetan sheep breeds. Results show that 37 genes were identified within overlapped genomic regions regarding Fst significantly associated with APS. Out of the 37 genes, we found that 8, 3 and 6 genes at chromosomes (chr.) 13, 23 and 27, respectively, were identified in the genomic regions with 1% top values of ZHp. We further analyzed the INDEL variation of 6 genes at chr.27 (X chromosome) in APS together with corresponding orthologs of 6 genes in Capra, Pantholops, and Bos Taurus. We found that an INDEL was located within 5′UTR region of HAG1 gene. This INDEL of HAG1 was strongly associated with the variation of APS, which was further confirmed by qPCR. Sheep breeds carrying "C-INDEL" of HAG1 have significantly greater body weight, shear amount, corpuscular hemoglobin and globulin levels, but lower body height, than those carrying "CA-INDEL" of HAG1. We concluded that "C-INDEL" variation of HAG1 gene confers better hypoxia tolerance in the highlands of Tibetan and explains well geographic distributions in this population. These results contribute to our understanding of adaptive responses to altitude and geographic adaptation in Tibetan sheep populations and will help to guide future conservation programs for Tibetan sheep native to Qinghai-Tibetan Plateau. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN), one of the main causes of end-stage renal disease, still remains as a challenge of clinical management. This study aimed to determine whether deficiency of the thromboxane (TX) prostanoid receptor (TP), which mediates the contractile activities of all prostanoids, alleviates the development of DN and if so, to examine the underlying mechanism(s). Diabetes was induced by high fat diet and streptozotocin injection in wild-type (WT) mice and those with TP deficiency (TP-/-). Here we show that WT and TP-/- mice developed diabetes with a similar blood glucose level; however, signs of renal functional impairments and pathologies occurred to a lesser extent in TP-/- than in WT mice. Also, the extent of an increase in the expression level of transforming growth factor-β1 (TGF-β1), a common pathological mediator of DN, in diabetic renal cortexes of TP-/- mice was lower than that of WT counterparts. Moreover, we noted that expression levels of cyclooxygenase (COX)-2 and calcium-dependent phospholipase A 2 (cPLA 2) as well as levels of prostaglandin E 2 and TXA 2 in diabetic renal cortexes were increased as compared to those of non-diabetic conditions. These results thus demonstrate that possibly due to up-regulated cPLA 2 and COX-2 that lead to increased prostanoid syntheses in diabetic renal cortexes, TP-/- alleviates DN development. In addition, our results suggest that such an effect of TP-/- might be related to the suppression of TGF-β1 up-regulation that is commonly associated with the disease condition. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cell (MSC) transplantation may serve as an important treatment modality in chronic kidney disease (CKD); however, the underlying mechanisms remain unclear. Advanced oxidation protein products (AOPP) have been demonstrated to induce renal tubular epithelial cell (RTEC) injury via autophagy inhibition. Therefore, the present study was performed to investigate the role of human umbilical cord-derived MSCs (hUC-MSCs) in RTEC autophagy. AOPP-treated HK-2 cells were co-cultured with hUC-MSCs or treated with recombinant humanized hepatocyte growth factor (HGF). Western blotting was used to detect the levels of autophagy-and PI3K/AKT/mTOR signaling pathway-related proteins, and immunofluorescence staining was used to detect the levels of autophagy-related proteins. The HGF protein levels in HK-2 cells and the hUC-MSC co-culture system were measured. The cells were subsequently treated with tivantinib, an HGF competitive inhibitor, and the levels of autophagy-related proteins were detected. Microtubule-associated protein 1 light chain 3B (LC3B) II/LC3B I (LC3II/LC3I) and beclin 1 protein levels were increased, while p62, PI3K, phosphorylated (p)-AKT and the p-mTOR protein levels were decreased in AOPP-treated HK-2 cells co-cultured with hUC-MSC, compared with the group treated with AOPP only. Furthermore, HGF expression was increased in AOPP-treated HK-2 cells co-cultured with hUC-MSC, compared with the group treated with AOPP alone. When HGF activity was inhibited using tivantinib, these effects on LC3II/LC3I, beclin 1, p62, PI3K, p-AKT, and p-mTOR expression were partially reversed. Furthermore, the effects of tivantinib were reversed by Ly294002. In conclusion, the present study revealed that hUC-MSCs partially reversed AOPP-mediated inhibition of autophagy in HK-2 cells via secretion of HGF, indicating that hUC-MSCs may serve as a potential therapy for preventing the progression of CKD. [ABSTRACT FROM AUTHOR]

Thousand grain weight (TGW) is one of the three crucial determinants of wheat (Triticum aestivum) grain yield. The identification of functional genes and development of closely linked markers are urgently needed for wheat yield improvements. In this study, quantitative trait locus (QTL) mapping for TGW was carried out using one RIL population in four environments. A total of 8 QTL controlling TGW were detected across four chromosomes. Of them, QGW4B.4-17 was confirmed as a major and stable QTL for TGW increases of 2.19–3.06 g and high PVE of 22.5–36.3% in three environments. It was located in an interval (Rht1-TaGW-4B) of 2 Mb in physical distance that contains the Rht1 locus. Three high-confidence (HC) genes were predicted as potential candidates according to their annotated functions and expression profiles. Furthermore, a cleaved amplified polymorphic sequence (CAPS) marker, TaGW-4B, was developed and verified in a panel of 205 wheat cultivars and showed a highly significant correlation with TGW, demonstrating high value for efficient marker-assisted selection. The study provided a basis for cloning the functional genes underlying the QTL and a practical and accurate marker for molecular breeding. [ABSTRACT FROM AUTHOR]

The axial compressive behavior of composite columns with recycled aggregate concrete (RAC)-filled steel tube and profile steel was examined through numerical investigations. The constitutive models of the RAC material, profile steel, and steel tube were assigned to respective elements in the columns. The experimental results were used to verify the finite element (FE) model. Results indicated that the FE model accurately predicts the deformation, stress, and load–strain curves of the columns. Then, the effects of RAC strength, steel tube strength, profile steel strength, profile steel ratio, and diameter-to-thickness ratio on the axial compressive behavior of the columns were evaluated through a parametric study. The increase in RAC strength, steel tube strength, and profile steel strength significantly affected the axial bearing capacities of the columns. However, deformation ability and ductility decreased gradually as the RAC strength and steel strength increased. The increase in the diameter-to-thickness ratio had a negative effect on the axial bearing capacities of the long columns. Based on the experimental research, FE analysis, and ultimate analysis method, a formula for the axial bearing capacity of the composite columns was proposed. The validity of the proposed formula was verified through the comparison of the results. The research conclusions can provide a reference for the design of composite columns. [ABSTRACT FROM AUTHOR]