Design and testing of a humanized porcine donor for xenotransplantation.

Recent human decedent model studies1,2 and compassionate xenograft use3 have explored the promise of porcine organs for human transplantation. To proceed to human studies, a clinically ready porcine donor must be engineered and its xenograft successfully tested in nonhuman primates. Here we describe the design, creation and long-term life-supporting function of kidney grafts from a genetically engineered porcine donor transplanted into a cynomolgus monkey model. The porcine donor was engineered to carry 69 genomic edits, eliminating glycan antigens, overexpressing human transgenes and inactivating porcine endogenous retroviruses. In vitro functional analyses showed that the edited kidney endothelial cells modulated inflammation to an extent that was indistinguishable from that of human endothelial cells, suggesting that these edited cells acquired a high level of human immune compatibility. When transplanted into cynomolgus monkeys, the kidneys with three glycan antigen knockouts alone experienced poor graft survival, whereas those with glycan antigen knockouts and human transgene expression demonstrated significantly longer survival time, suggesting the benefit of human transgene expression in vivo. These results show that preclinical studies of renal xenotransplantation could be successfully conducted in nonhuman primates and bring us closer to clinical trials of genetically engineered porcine renal grafts.

The hepcidin-ferroportin axis modulates liver endothelial cell BMP expression to influence iron homeostasis in mice.

The liver hormone hepcidin regulates systemic iron homeostasis to provide enough iron for vital processes while limiting toxicity. Hepcidin acts by degrading its receptor ferroportin (encoded by Slc40a1) to decrease iron export to plasma. Iron controls hepcidin production in part by inducing liver endothelial cells (LECs) to produce bone morphogenetic proteins (BMPs), which activate hepcidin transcription in hepatocytes. Here, we used in vitro and in vivo models to investigate whether ferroportin contributes to LEC intracellular iron content to modulate BMP expression and thereby hepcidin. Quantitative proteomics of LECs from mice fed different iron diets demonstrated an inverse relationship between dietary iron and endothelial ferroportin expression. Slc40a1 knockdown primary mouse LECs and endothelial Slc40a1 knockout mice exhibited increased LEC iron and BMP ligand expression. Endothelial Slc40a1 knockout mice also exhibited altered systemic iron homeostasis with decreased serum and total liver iron but preserved erythropoiesis. Although endothelial Slc40a1 knockout mice had similar hepcidin expression as control mice, hepcidin levels were inappropriately high relative to iron levels. Moreover, when iron levels were equalized with iron treatment, hepcidin levels were higher in endothelial Slc40a1 knockout mice than controls. Finally, LEC ferroportin levels were inversely correlated with hepcidin levels in multiple mouse models, and treatment of hepcidin-deficient mice with mini-hepcidin decreased LEC ferroportin expression. Overall, these data show that LEC ferroportin modulates LEC iron and consequently BMP expression to influence hepcidin production. Furthermore, LEC ferroportin expression is regulated by hepcidin, demonstrating bidirectional communication between LECs and hepatocytes to orchestrate systemic iron homeostasis.

The epithelial polarity genes frazzled and GUK-holder adjust morphogen gradients to coordinate changes in cell position with cell fate specification.

Morphogenetic gradients specify distinct cell populations within tissues. Originally, morphogens were conceived as substances that act on a static field of cells, yet cells usually move during development. Thus, the way cell fates are defined in moving cells remains a significant and largely unsolved problem. Here, we investigated this issue using spatial referencing of cells and 3D spatial statistics in the Drosophila blastoderm to reveal how cell density responds to morphogenetic activity. We show that the morphogen decapentaplegic (DPP) attracts cells towards its peak levels in the dorsal midline, whereas dorsal (DL) stalls them ventrally. We identified frazzled and GUK-holder as the downstream effectors regulated by these morphogens that constrict cells and provide the mechanical force necessary to draw cells dorsally. Surprisingly, GUKH and FRA modulate the DL and DPP gradient levels and this regulation creates a very precise mechanism of coordinating cell movement and fate specification.

The prodomain of bone morphogenetic protein 2 promotes dimerization and cleavage of BMP6 homodimers and BMP2/6 heterodimers.

Bone morphogenetic protein 2 (BMP2) and BMP6 are key regulators of systemic iron homeostasis. All BMPs are generated as inactive precursor proteins that dimerize and are cleaved to generate the bioactive ligand and inactive prodomain fragments, but nothing is known about how BMP2 or BMP6 homodimeric or heterodimeric precursor proteins are proteolytically activated. Here, we conducted in vitro cleavage assays, which revealed that BMP2 is sequentially cleaved by furin at two sites, initially at a site upstream of the mature ligand, and then at a site adjacent to the ligand domain, while BMP6 is cleaved at a single furin motif. Cleavage of both sites of BMP2 is required to generate fully active BMP2 homodimers when expressed in Xenopus embryos or liver endothelial cells, and fully active BMP2/6 heterodimers in Xenopus. We analyzed BMP activity in Xenopus embryos expressing chimeric proteins consisting of the BMP2 prodomain and BMP6 ligand domain, or vice versa. We show that the prodomain of BMP2 is necessary and sufficient to generate active BMP6 homodimers and BMP2/6 heterodimers, whereas the BMP6 prodomain cannot generate active BMP2 homodimers or BMP2/6 heterodimers. We examined BMP2 and BMP6 homodimeric and heterodimeric ligands generated from native and chimeric precursor proteins expressed in Xenopus embryos. Whereas native BMP6 is not cleaved when expressed alone, it is cleaved to generate BMP2/6 heterodimers when co-expressed with BMP2. Furthermore, BMP2-6 chimeras are cleaved to generate BMP6 homodimers. Our findings reveal an important role for the BMP2 prodomain in dimerization and proteolytic activation of BMP6.

Adsorption thermodynamics and kinetics of nanomaterials: theory and experimental insight into nano-effect.

Nanomaterials have excellent adsorption performance due to nano-effect and have been widely used in many fields. The adsorption performance of nanomaterials depends on their adsorption thermodynamics and kinetics. Here, the thermodynamic and kinetic equations of adsorption for spherical nanoparticles are first derived in theory. The mechanisms and regularities of influences of nano-effect on thermodynamics and kinetics, using nano-CdS adsorption of methylene blue as a probe, were investigated. The results show that there are significant influences of nano-effect (i.e., interface area effect and interface tension effect) on the thermodynamics and kinetics of nanoparticle adsorption. When the particle radius is larger and beyond the nanometer scale (∼100 nm), the nano-effect can be neglected. When the radius of the nanoparticle is within 10-50 nm, the nano-effect of adsorption is mainly the interface area effect. When the radius is less than 10 nm, the influences of both the interface area effect and the interface tension effect on adsorption thermodynamics and kinetics become more significant. The theoretic equations and experimental insights in the present work could provide a significant basis and reference for improving and perfecting the adsorption theory involving nanomaterials and provide guidelines for the explanations of adsorption mechanisms as well as the selection of adsorbents.

Determination of Interfacial Tension of Nanomaterials and the Effect of Particle Size on Interfacial Tension.

The unique physical and chemical properties and performances of nanomaterials are closely related to the interfacial tension. However, there is no method to accurately measure the interfacial tension of nanomaterials. In addition, the effect of particle size on the interfacial tension of nanoparticles is unclear, and there exist conflicting conclusions about the value and sign of Tolman length. In this paper, a novel method of determining the interfacial tension (solid-liquid and solid-gas interfaces), temperature coefficient of interfacial tension, and Tolman lengths of nanomaterials by adsorption thermodynamics and kinetics was presented. The interfacial tension and its temperature coefficient of the solid-liquid interface of nano cadmium sulfide before adsorption were obtained, and further, the Tolman length was also obtained. The experimental results show that the particle size of nanoparticles has significant effects on the interfacial tension and its temperature coefficient. When the radius is larger than 10 nm, the interfacial tension and its temperature coefficient are almost constant with the decrease of the radius. When the radius is less than 10 nm, the interfacial tension decreases sharply and the temperature coefficient increases sharply with the decrease of the radius, and the temperature coefficient of the interfacial tension is negative. The Tolman length of the solid-liquid interface of nanoparticles is proved to be positive, and the particle size also has a significant effect on the Tolman length. The Tolman length decreases with the decrease of particle size. However, the effects of particle size on the Tolman length become significant only when the particle radius approach or reach the order of magnitudes of molecular (or atomic) radius. The effects of particle size on interfacial tension and Tolman length of nano cadmium sulfide obtained in this paper can provide significant references for the research and applications of interface thermodynamics of other nanomaterials.

Size-dependent melting thermodynamics of nanorods in theory and experiment.

Compared with other morphological nanomaterials, nanorods have many unique properties that are closely related to their thermal stability. However, current studies on melting thermodynamic theory of nanorods are still not perfect, and the mechanism and the quantitative regularities of the effect of size of nanorods on melting thermodynamics still remain unclear. Herein, we proposed a melting model of nanorods, derived the thermodynamic relations (free of any adjustable parameters) between the melting temperature, melting enthalpy, and melting entropy, respectively, and the radius of nanorods, and discussed the mechanism of the effect of nanorods and the size dependences of melting thermodynamic properties. Experimentally, taking the melting of Se nanorods as an experimental system, Se nanorods with different diameters were prepared by a Na2SeSO3 disproportionation method, and then the melting temperature and melting thermodynamic properties were determined by differential scanning calorimetry. The effects of the diameter of Se nanorods on the melting temperature and the melting thermodynamic properties were obtained. The experimental results are consistent with the theoretical relations. Both theoretical and experimental results demonstrate that the radius and length of nanorods have significant effects on the melting temperature and the melting thermodynamic properties; for nanorods with a large aspect ratio, the main factors of influence are interfacial tension and radius. Compared with spherical nanoparticles with the same radius, the reduced values of the melting temperature and the thermodynamic properties of nanorods are just half of those corresponding to spherical nanoparticles; the melting temperature, the melting enthalpy, and the melting entropy decrease with the decrease in the radius, and when the radius exceeds 10 nm, these physical quantities are all linearly related to the reciprocal of the radius. The theory can describe the quantitative size-dependent melting thermodynamic properties of nanorods, explain and predict the melting behaviors of nanorods.

Size and shape dependences of the adsorption kinetics of malachite green on nano-MgO: a theoretical and experimental study.

Compared with bulk materials, there is a considerable difference in the adsorption kinetics of nanoparticles, which mainly depend on particle size and shape. Herein, by introducing the shape factor, we have derived the relations between the kinetic parameters of adsorption and the particle size of nanoparticles of different shapes. Then, the influence of the regularities and mechanisms of particle size and shape on the kinetic parameters of adsorption were discussed. In the experiment, spherical nano-MgO and cubic nano-MgO of different particle sizes were synthesized via a sol-gel method, the kinetic parameters of the adsorption of malachite green on nano-MgO were determined, and the influence of the regularities of particle size and shape on the adsorption kinetic parameters were obtained. The experimental results show that shape and particle size may significantly influence the kinetic parameters of adsorption. For the adsorption of nano-MgO with the same equivalent particle diameter, compared to spherical shapes, the rate constant of adsorption k for cubic shapes is larger, while the apparent activation energy Ea and the pre-exponential factor A are smaller. For the adsorption of spherical or cubic nano-MgO, k increases with decreasing particle size, while Ea and A decrease, and there exist good linear relationships between ln k, Ea, ln A and the reciprocal of particle size. The experimental results are well in agreement with the theoretical relations. Furthermore, k is influenced by the shape factor, Ea by the shape factor and the specific surface enthalpy, and A by the shape factor and the temperature coefficient of surface tension. The kinetic theory of adsorption can quantitatively describe the influence of the regularities and mechanisms of particle size and shape on the adsorption kinetics of nanoparticles and provide significant guidance for the research and the application of nano-adsorptions in the related fields.

Suhuai suckling piglet hindgut microbiome-metabolome responses to different dietary copper levels.

Unabsorbed copper accumulates in the hindgut of pigs that consume high levels of dietary copper, which enhances the coselection of antibiotic-resistant bacteria and is considered detrimental to the environment and to porcine health. In our study, a combination of 16S rRNA pyrosequencing and nontargeted metabolomics was used to investigate the microbiome-metabolome responses to dietary copper levels in the hindgut of suckling piglets. The results showed that the dietary copper level affected the abundance of several Clostridia genera and that the relative abundance of butyrate-producing bacteria, such as Coprococcus, Roseburia, and Acidaminococcus, was reduced in the 300 mg kg-1 (high) Cu group. Metabolomic analysis revealed that dietary copper levels affected protein and carbohydrate metabolites, protein biosynthesis, the urea cycle, galactose metabolism, gluconeogenesis, and amino acid metabolism (including the metabolism of arginine, proline, ß-alanine, phenylalanine, tyrosine, and methionine). Furthermore, Pearson's correlation analysis showed that the abundance levels of Coprococcus (family Lachnospiraceae) and operational taxonomic unit (OTU) 18 (family Ruminococcaceae) were positively correlated with energy metabolism pathways (gluconeogenesis, glycolysis, and the pentose phosphate pathway). The abundance of Streptococcus was negatively correlated with amino acid metabolism pathways (protein biosynthesis, glycine, serine, threonine, methionine, phenylalanine, and tyrosine metabolism), and OTU583 and OTU1067 (family Rikenellaceae) were positively correlated with amino acid metabolism pathways. These results suggest that the copper levels consumed by LC (low-copper group) versus HC (high-copper group) animals alter the composition of the gut microbiota and modulate microbial metabolic pathways, which may further affect the health of suckling piglets.

A controlled heat stress during late gestation affects thermoregulation, productive performance, and metabolite profiles of primiparous sow.

Heat stress (HS) alters metabolic parameters and reduces productive performance in lactating sows. However, the impact of HS on metabolomic profiles of sows during late gestation is not fully understood. We present here, a study investigating the productive performance and metabolic responses in sows when exposed to HS during late gestation. Twelve first-parity Landrace × Large White F1 sows were randomly assigned into two environmental treatments including the thermoneutral (TN) (18-22 °C; n = 6) and HS (28-32 °C; n = 6) conditions from 85 d of gestation until farrowing. Rectal temperature (RT), respiration rates (RR), and surface temperature (ST) were measured every 4 h from 0800 h to 2000 h during the 2nd week. Farrowing and litter Data, as well as duration of eating, were monitored to assess sows' productive performance. Blood biochemical parameters and urinary metabolomic profiles were measured on d107 of gestation to analyze the host metabolic responses. Our results show that HS increased RT, RR, and ST (P < 0.0001). Duration of parturition was prolonged during the delivery in HS group (P < 0.05). Piglet body weight (BW) at d 10 and weaning were reduced by 18% and 17% respectively due to maternal HS (P < 0.001). Duration of eating increased as a result of HS (P < 0.001), consistent with the significant changes observed in serum ghrelin (P < 0.05). Moreover, serum ACTH, cortisol, insulin, creatinine, and BUN saw increase as well (P < 0.05). Plasma NEFA were elevated by HS (P < 0.001). Additionally, HS elevated (VIP>1, log2fold change>0.585, and P < 0.05) the relative concentrations of 5-aminovaleric acid, ß-alanine, cysteine, isoleucine, glyceric acid, erythronic acid, mannitol, erythritol, 2-methyl-1,3-butanediol, and pantothenic acid in urine. These ten metabolites mainly affected the pantothenate and CoA biosynthesis, ß-alanine metabolism, and glycerolipid metabolism in pregnant sows. In summary, our study suggests that the controlled HS during late gestation elevates thermal responses, reduces productive performance, and more importantly, enhances the catabolism of lipid and protein of first-parity pregnant sow.

Size-Dependent Thermodynamics and Kinetics of Adsorption on Nanoparticles: A Theoretical and Experimental Study.

Owing to their excellent adsorption properties compared with those of the corresponding bulk materials, nanoparticles have been widely applied in many fields. Their properties depend on the thermodynamics and kinetics of adsorption, which depend on the particle size. In this paper, we present universal theories of the thermodynamics and kinetics for nanoadsorption that have been developed over the past few years. Theoretically, we have derived relationships between the adsorption thermodynamic properties and the particle size, as well as those between the adsorption kinetic parameters and the particle size. Moreover, we discuss the regularities and mechanisms of influence of the particle size on the thermodynamics and kinetics of adsorption. Experimentally, taking the adsorption of methyl orange on nano-CeO2 in aqueous solution as a system, we have studied the size-dependent thermodynamics and kinetics of the system, and the size dependences were confirmed to be consistent with the theoretical relationships. The results indicate that particle size has a significant effect on the thermodynamic properties and kinetic parameters of adsorption: with decreasing particle size of nano-CeO2, the adsorption equilibrium constant K⊖ and the adsorption rate constant k increase, while the molar Gibbs free energy of adsorption Δads Gm⊖, the molar adsorption entropy Δads Sm⊖, the molar adsorption enthalpy Δads Hm⊖, the adsorption activation energy Ea, and the adsorption pre-exponential factor A all decrease. Indeed, ln K⊖, Δads Gm⊖, Δads Sm⊖, Δads Hm⊖, ln  k, Ea, and ln  A are each linearly related to the reciprocal of particle size. Furthermore, thermodynamically, Δads Gm⊖ and ln  K⊖ are influenced by the molar surface area and the difference in surface tensions, Δads Sm⊖ is influenced by the molar surface area and the difference in temperature coefficients of surface tension, and Δads Hm⊖ is influenced by the molar surface area, the difference in surface tensions, and the difference in temperature coefficients of surface tension. Kinetically, Ea is influenced by the partial molar surface enthalpy of the nanoadsorbent, ln  A is influenced by the partial molar surface entropy, and ln  k is influenced by the partial molar surface Gibbs energy. The theories can quantitatively describe adsorption behavior on nanoparticles, explain the regularities and mechanisms of influence of particle size, and provide guidance for the research and application of nanoadsorption.

Determination Method and Size Dependence of Interfacial Tension between Nanoparticles and a Solution.

Interfacial tension plays an important role in the processes of preparation, research, and application of nanomaterials. Because the interfacial tension is fairly difficult to be determined by experiments, it is still unclear about the effect of particle size on interfacial tension. In this paper, we proposed a method to determine the interfacial tensions and its temperature coefficients by determining the electrode potential of the nanoparticle electrode. Nano-Au with different radii (from 0.9 to 37.4 nm) in an aqueous solution was taken as a research system; we determined the interfacial tension and its temperature coefficient of the interface and discussed the size dependence. At the same time, we found surprisingly that this method can also be applied to determine the Tolman length and the atomic radius. The results show that the particle size of nano-Au has remarkable influences on the interfacial tension and its temperature coefficient. As the particle size decreases, the interfacial tension and the absolute value of its temperature coefficient increase. With the decrease of radius, the influences of the particle size on the interfacial tension and its temperature coefficient become more significant, whereas the influences can be neglected when the radius exceeds 10 nm. In addition, the results also show that the Tolman length is a negative value, and temperature has little effect on the Tolman length. This research can provide a new method to conveniently and reliably determine the interfacial tension on interfaces between nanoparticles and solutions, the temperature coefficients, the Tolman lengths, and the atomic radii; and the size dependences can provide important references for preparation, research, and application of nanomaterials.

Shape dependence of thermodynamics of adsorption on nanoparticles: a theoretical and experimental study.

Nanomaterials have excellent adsorption performance, which mainly depends on the adsorption thermodynamics that is related to the shape of the nanoparticles that make up the nanomaterial, but the effects of shape on the thermodynamics of adsorption are not fully clear. In this paper, theoretically, the general formulae of adsorption thermodynamic properties for nanoparticles with different shapes and different sizes were derived, and the influencing regularities and mechanisms on adsorption thermodynamic properties were discussed. Experimentally, the influences of the shape and size of nano-CeO2 on the thermodynamics of adsorption were studied in aqueous solution. The experiment results showed that the shape has significant influences on the thermodynamics of adsorption, and the smaller the particle size, the more significant the effects of shape on the thermodynamics. For the adsorption of nano-CeO2 with different shapes and the same equivalent particle size, compared with the sphere, the equilibrium constant of adsorption for the octahedron is larger, while the molar Gibbs free energy of adsorption , the molar adsorption enthalpy of adsorption and the molar adsorption entropy of adsorption are smaller. For the adsorption of nano-CeO2 with the same shape, with the decreasing particle size, increases, while , and decrease; and , , and are each linearly related to the reciprocal of particle size. The experimental results are consistent with the theoretical relations. The theories can quantitatively describe the adsorption behavior on nanoparticles, explain the regularities and mechanisms of influence of shape, and provide guidance for the research and application of nanoadsorption.

Synthesis of TiO2/Fly Ash Cenospheres by Sol-Gel Method and Their Photacatalytic Activities Under Visible Light.

Fly ash is a solid waste discharged from thermal power plant. Specific surface area of floating fly ash cenospheres (FACs) would increase after it was modified. The photocatalytic composite of TiO2/FACs was successfully synthesized by sol-gel method using the carrier of modified FACs and tetrabutyl titanate as starting materials. The different influence factors on the photocatalytic performance of TiO2/FACs composites were characterized through SEM, EDS, XRD, UV-vis DRS and BET surface measurements. The UV-vis DRS spectra revealed that the absorption edge of TiO2 is 387 nm while that of TiO2/FACs photocatalysts red-shifts to 500 nm. Photocatalytic activity of TiO2/FACs was evaluated by the photocatalytic depigmentation of methyl orange solution (MO, 20 mg L-1, pH = 6.3) under visible light irradiation. It was found that the specific surface area, surface roughness and activity of FACs were increased by NaOH solution activation. The degradation rate of MO reaches 52% in 180 min under the visible light illumination. But too much FACs could decrease its photocatalytic activity and degradation rate. And the recovery test indicated that TiO2/FACs photocatalyst was rather stable, easy to recover from the treated wastewater.

Persistent Methyl Orange Degradation Ability of MgAl2O4:(Pr3+,Dy3+)/M-TiO2 Luminescent Photocatalyst.

Metal ions (Cr, Ni, Co) doped titania (M-TiO2) coupled with the long after glow phosphor MgAl2O4:(Pr3+, Dy3+) particles were synthesized by the sol-gel method, with the best mass ratio of MgAl2O4:(Pr3+, Dy3+) to M-TiO2 as 4:6. MgAl2O4:(Pr3+, Dy3+)/M-TiO2 had the persistent methyl orange (MO) photocatalytic degradation ability and the photocatalytic degradation went on reacting more than 90 min in dark after turning off the light. MgAl2O4:(Pr3+, Dy3+) emitted the light as a light source in dark which was absorbed by M-TiO2. The differences of MgAl2O4:(Pr3+, Dy3+)/Cr-TiO2, MgAl2O4:(Pr3+, Dy3+)/Ni-TiO2 and MgAl2O4:(Pr3+, Dy3+)/Co-TiO2 might be attributed to the difference in the metal ions doping. The composite MgAl2O4:(Pr3+, Dy3+)/Cr-TiO2 revealed the highest ability of persistent photocatalytic degradation methyl orange. Different metal ions doping made the TiO2 with different band gap.

Preparation and Properties of Phenol Imprinted Polymers Based on Silica Modified Multi-Walled Carbon Nanotubes.

A novel molecular imprinted polymers (MIP) based on SiO2-modified multi-walled carbon nanotubes (MWNTs@SiO2) was successfully synthesized by combining a surface molecular imprinting technique with a sol­gel method using phenol as a template molecule, 3-aminopropyltriethoxysilane as functional monomer and tetraethoxysilicane as a cross-linker in ethanol solution. Scanning electron microcopy (SEM) and X-ray diffraction (XRD) were used to characterize and analysis the structure and morphology of the molecular imprinting composite, and then studied the isotherm adsorption experiments, selective experiments and dynamic curve. The isotherm adsorption data were further processed with a Scatchard equation to evaluate the adsorption properties of the MWNTs@SiO2-MIP. The results showed that imprinted polymeric layer was successfully grafted to the surface of MWNTs, the imprinted material had a binding site for the template and apparent maximum amount Q max = 19.902 mg/g, the maximum imprint factor (α) for the template was 3.484 and the maximum selectivity factor (ß) up to 3.440, so the imprinted materials could be applied to the separation of trace phenol.

The BMP2 prodomain promotes dimerization and cleavage of BMP6 homodimers and BMP2/6 heterodimers in vivo.

Bone morphogenetic protein 2 (BMP2) and BMP6 are key regulators of systemic iron homeostasis. All BMPs are generated as inactive precursor proteins that dimerize and are cleaved to generate the bioactive ligand and inactive prodomain fragments, but nothing is known about how BMP2 or BMP6 homodimeric or heterodimeric precursor proteins are proteolytically activated. Here, we conducted in vitro cleavage assays, which revealed that BMP2 is sequentially cleaved by furin at two sites, initially at a site upstream of the mature ligand, and then at a site adjacent to the ligand domain, while BMP6 is cleaved at a single furin motif. Cleavage of both sites of BMP2 is required to generate fully active BMP2 homodimers when expressed in Xenopus embryos or liver endothelial cells, and fully active BMP2/6 heterodimers in Xenopus . We analyzed BMP activity in Xenopus embryos expressing chimeric proteins consisting of the BMP2 prodomain and BMP6 ligand domain, or vice versa. We show that the prodomain of BMP2 is necessary and sufficient to generate active BMP6 homodimers and BMP2/6 heterodimers, whereas the BMP6 prodomain cannot generate active BMP2 homodimers or BMP2/6 heterodimers. We examined BMP2 and BMP6 homodimeric and heterodimeric ligands generated from native and chimeric precursor proteins expressed in Xenopus embryos. Whereas native BMP6 is not cleaved when expressed alone, it is cleaved to generate BMP2/6 heterodimers when co-expressed with BMP2. Furthermore, BMP2-6 chimeras are cleaved to generate BMP6 homodimers. Our findings reveal an important role for the BMP2 prodomain in dimerization and proteolytic activation of BMP6.

Encapsulated Essential Oils Improve the Growth Performance of Meat Ducks by Enhancing Intestinal Morphology, Barrier Function, Antioxidant Capacity and the Cecal Microbiota.

The objective of this study was to evaluate the effects of encapsulated essential oils (EOs) on the gut microbiota, growth performance, intestinal morphology, antioxidant properties and barrier function of meat-type ducks. A total of 320 male Cherry Valley ducks (1 day old), were randomly assigned to four dietary experimental groups with eight replicates of ten ducks each. The groups consisted of the CON group (basal diet), the HEO group (basal diet + EO 1000 mg/kg), the LEO group (basal diet + EO 500 mg/kg), and the ANT group (basal diet + chlortetracycline 50 mg/kg). Our findings indicated that ducks fed with EO 1000 mg/kg had greater average daily feed intake (ADFI), average daily gain (ADG), and body weight (BW) and a lower feed conversion ratio (FCR) than the other groups. The serum concentration of TG reduced in the HEO (p > 0.05) and LEO (p < 0.05) groups on day 42, while the concentration of CHOL increased with the EO concentration in the LEO (p > 0.05) and HEO (p < 0.05) groups. No differences were observed in the ileal mucosa for the activities of SOD, MPO and GSH-PX after EO dietary treatment. Dietary supplementation with EOs significantly increased the villus heights (p < 0.01) and the ratio of villus height to crypt depth (c/v) in the duodenum and jejunum of ducks. Moreover, the mRNA expressions of Claudin1 and Occludin in the jejunal mucosa were observed to be higher in the LEO and HEO groups rather than the CON and ANT groups on d 42. The α diversity showed that the HEO group improved the bacterial diversity and abundance. The ß diversity analysis indicated that the microbial structures of the four groups were obviously separated. EO dietary supplementation could increase the relative abundance (p < 0.01) of the Bacteroidetes phylum, Bacteroidaceae family, and Bacteroides, Desulfovibrio, Phascolarctobacterium, and Butyricimonas genera in the cecal microbiota of ducks. We demonstrated significant differences in the bacterial composition and functional potential of the gut microbiota in ducks that were fed either an EO diet or a basal diet. Therefore, supplemented EOs was found to have a positive effect on the growth performance and intestinal health of ducks, which was attributed to the improvement in cecal microbiota, intestinal morphology, and barrier function.

Effects of a functional fatty acid blend on growth performance, intestinal morphology, and serum profiles in weaned piglets.

OBJECTIVE: The objective of this study was to determine whether dietary supplementation with a functional fatty acid blend (FA) that contains 31.4% butyric acid and 4.99% medium-chain FA improve growth performance, antioxidant capacity, immunity status, and anti-inflammatory ability in weaned piglets. METHODS: One hundred and forty-four healthy piglets (Duroc×Landrace×Yorkshire) with an average body weight (BW) of 7.98±3.43 kg were randomly divided into three groups with six replicate pens and eight piglets per pen: Normal control (NC): a corn-soybean basal diet; FA1: a basal diet supplemented with 1,000 mg/kg of a functional FA; FA2: a basal diet supplemented with 2,000 mg/kg of a functional FA. The experiment lasted for 28 d. On d 14 and 28, one piglet in each pen from NC and FA2 groups was randomly selected for antioxidative index and immunoglobulins. On d 28, one piglet in each pen from NC and FA2 groups was randomly selected for intestinal morphology and inflammatory factor. RESULTS: We observed that FA supplementation linearly increased (p<0.05) average daily gain and the final BW. There was higher (p<0.05) catalase on d 14, and immunoglobulin (Ig) A and IgM on d 28 in piglets supplemented with FA2 than in the NC group. Moreover, dietary FA2 reduced (p<0.05) crypt depth of ileum in piglets. The concentrations of tumor necrosis factor-α, interleukin (IL)-1ß, IL-8, and IL-10 in jejunum were lower (p<0.05) in the FA2 group compared with the NC group. CONCLUSION: Therefore, the overall results suggests that the FA may help to improve gut health, antioxidant status, and immune parameters resulting in the improvement of growth performance.

Effects of essential oil coated with glycerol monolaurate on growth performance, intestinal morphology, and serum profiles in weaned piglets.

OBJECTIVE: This study aimed to investigate the effects of essential oil coated with glycerol monolaurate (GML) on the growth performance, intestinal morphology, and serum profiles of weaned piglets. METHODS: A total of 144 weaned piglets (Duroc×[Landrace×Yorkshire], average weight 8.07±3.33 kg) were randomly assigned to three groups with six replicate pens and eight piglets per pen: i) CON: a corn-soybean basal diet; ii) LEG: with 1,000 mg/kg essential oil coated with GML; and iii) HEG: with 2,000 mg/kg essential oil coated with GML. RESULTS: Results showed that average daily gain was increased (p<0.05) linearly by essential oil coated with GML supplementation on day 14 to 28 and day 0 to 28 compared with the CON group. Dietary supplementation with HEG increased (p<0.05) total antioxidant capacity and catalase activity on day 14, and immunoglobulin A (IgA) and IgM concentration on day 28 and tended to increase IgG on day 28. In addition, the crypt depth in the jejunum was reduced (p<0.05), and villus height and villus height/crypt depth in the ileum were increased (p<0.05) in the HEG group compared with the CON group. Moreover, lower (p<0.05) concentrations of tumor necrosis factor-α, interferon-γ, interleukin-1ß (IL-1ß), IL-8, and IL-10 were observed in the jejunum of piglets supplemented with HEG compared with the CON group. In addition, dietary HEG tended to decrease IL-6 level in the jejunum of piglets compared with the CON group. CONCLUSION: Dietary essential oil coated with GML can improve growth performance of weaned piglets. Moreover, supplementing 2,000 mg/kg essential oil coated with GML was demonstrated to improve antioxidant ability, and intestinal morphology, and reduce jejunal inflammatory factor levels.