Search

Recent studies have shown that l-proline (proline) is an antioxidant to protect cells from oxidative stress in vivo and in vitro. Glutathione (GSH) is a major cellular redox regulator involved in controlling redox balance and is regarded as one of the key indices to predict the cytoplasmic maturation of oocytes. The objectives of this study are to investigate the effect of proline on the developmental potential of mouse oocytes and to determine the role of gap junctional communication (GJC) on intraoocyte GSH concentration during in vitro maturation (IVM). Compared with control (0 mmol/L), 0.5 mmol/L proline supplementation enhanced rates of activated oocytes, 2-cell and 4-cell embryos, and blastocysts. Furthermore, 0.25 and 0.5 mmol/L proline supplementation markedly upregulated mRNA expression of glutamate-cysteine ligase catalytic subunit (GCLC) and glutamate-cysteine ligase modifier subunit (GCLM) in oocytes and cumulus cells, enhanced GSH concentration in oocytes, and reduced reactive oxygen species (ROS) level in oocytes. Interestingly, carbenoxolone disodium salt (CBX) treatment reduced GSH concentration in oocytes and the rate of early embryo development without proline incubation. Notably, CBX-triggered reduction in the rates of the number of 2-cell and 4-cell embryos and blastocysts were rescued by 0.5 mmol/L proline supplementation. Collectively, these results indicate a novel functional role of proline in oocyte cytoplasmic maturation and regulation of glutathione-related redox homeostasis.

The E2 promoter binding factor 1 (E2F1) and the Wnt/β-catenin signaling are crucial in regulating metabolic homeostasis including obesity. The β-catenin interacting protein 1 (CTNNBIP1), also known as the inhibitor of β-catenin and TCF4 (ICAT), is required for E2F1 to inhibit the activity of β-catenin. However, the role of ICAT in E2F1 regulating obesity-related metabolic disorders remains unknown. In the present study, male adipose tissue-specific ICAT knockout (ICAT

During selective laser melting (SLM) process, the correlation between thermal behavior and complex microstructure must be clarified. The present study investigates the effect of laser power and scan speed on thermal behavior and solidification structures of SLM-produced high strength tool steel. A three-dimensional finite element model was built to simulate the thermal behavior in SLM process. The simulation results show that correlativity exists between the process parameters (laser energy density) and the maximum temperature, cooling rate, temperature gradient and solidification rate. Scan speed has more significant impact on the cooling rate and solidification rate than laser power. The sub-grain patterns of the part presents predominantly cellular, elongated cellular and columnar structure. The formation of these sub-grain microstructures in the molten pool was controlled by the gradient cooling rate (from 5.6×105 to 3.4×106 °C/s) and temperature gradient (from 5.0 to 30 °C/μm). The columnar structure are elongated with the increment of the temperature gradient. The grain size of the microstructure become finer with the increase of laser power or scan speed. And the gradient microstructure has a significant impact on its microhardness properties.

Background: Docosahexaenoic acid-acylated phloridzin (PZ-DHA), a novel polyphenol fatty acid ester derivative, is synthesized through an acylation reaction of phloridzin (PZ) and docosahexaenoic acid (DHA). PZ-DHA is more stable than DHA and exhibits higher cellular uptake and bioavailability than PZ. Objective: The study aims to investigate the effects of PZ-DHA on insulin resistance in the skeletal muscle and the related mechanisms; we used palmitic acid (PA)-treated C2C12 myotubes as an insulin resistance model. Results: We found that PZ-DHA increased the activity of AMP-activated protein kinase (AMPK) and improved glucose uptake and mitochondrial function in an AMPK-dependent manner in untreated C2C12 myotubes. PZ-DHA treatment of the myotubes reversed PA-induced insulin resistance; this was indicated by increases in glucose uptake and the expression of membrane glucose transporter 4 (Glut4) and phosphorylated Akt. Moreover, PZ-DHA treatment reversed PA-induced inflammation and oxidative stress. These effects of PZ-DHA were mediated by AMPK. Furthermore, the increase in AMPK activity, improvement in insulin resistance, and decrease in inflammatory and oxidative responses after PZ-DHA treatment diminished upon co-treatment with a liver kinase B1 (LKB1) inhibitor, suggesting that PZ-DHA improved AMPK activity by regulating its upstream kinase, LKB1. Conclusion: The effects of PZ-DHA on insulin resistance in C2C12 myotubes may be mediated by the LKB1- AMPK signaling pathway. Hence, PZ-DHA is a promising therapeutic agent for insulin resistance in type 2 diabetes.

Muscle weakness affects physical activity and quality of life of patients. Serine, a nutritionally non-essential amino acid has been reported to enhance protein synthesis and implicate in biosynthesis of multiple bioactive molecules. It remains unknown whether it can protect mice against oxidative stress-induced muscles weakness. This study was conducted to test the hypothesis that serine administration alleviates doxorubicin-induced oxidative damage in skeletal muscle of mice. Mice pre-treated with or without serine were intraperitoneally injected with either doxorubicin or equal volume of saline. Reactive oxygen species (ROS) accumulation, activity of antioxidant enzymes, oxidation product of protein, DNA, and lipid, activity of mitochondrial complex, and protein level of nuclear-factor-erythroid-2-related factor 2 (NRF2)/constitutive-androstane-receptor (CAR) signaling in skeletal muscle of mice were determined. Compared with the control, doxorubicin exposure led to oxidative damage as shown by increased ROS accumulation, decreased activity of antioxidant enzymes, and enhanced oxidative product of protein, DNA, and lipid in the skeletal muscle of mice. These effects of doxorubicin were associated with increased activity of complex I and reduced glutathione. Interestingly, doxorubicin-induced oxidative damage was alleviated by serine administration. Further study showed that the beneficial effect of serine was associated with enhanced NRF2/CAR signaling. Our result showed that serine attenuated doxorubicin-induced muscle weakness in mice. Serine supplementation might be a nutritional strategy to improve the function of skeletal muscle in patients exposed to doxorubicin.

L-Proline (proline) in amniotic fluid was markedly increased during pregnancy in both pigs and sheep. However, in vivo data to support a beneficial effect of proline on fetal survival are not available. In this study, pregnant C57BL/6J mice were fed a purified diet supplemented with or without 0.50% proline from embryonic day 0.5 (E0.5) to E12.5 or term. Results indicated that dietary supplementation with proline to gestating mice enhanced fetal survival, reproductive performance, the concentrations of proline, arginine, aspartic acid, and tryptophan in plasma and amniotic fluid, while decreasing the concentrations of ammonia and urea in plasma and amniotic fluid. Placental mRNA levels for amino acid transporters, including Slc36a4, Slc38a2, Slc38a4, Slc6a14, and Na+/K+ ATPase subunit-1α (Atp1a1), fatty acid transporter Slc27a4, and glucose transporters Slc2a1 and Slc2a3, were augmented in proline-supplemented mice, compared with the control group. Histological analysis showed that proline supplementation enhanced labyrinth zone in the placenta of mice at E12.5, mRNA levels for Vegf, Vegfr, Nos2, and Nos3, compared with the controls. Western blot analysis showed that proline supplementation increased protein abundances of phosphorylated (p)-mTORC1, p-ribosomal protein S6 kinase (p70S6K), and p-eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), as well as the protein level of GCN2 (a negative regulator of mTORC1 signaling). Collectively, our results indicate a novel functional role of proline in improving placental development and fetal survival by enhancing placental nutrient transport, angiogenesis, and protein synthesis.

The complex metallurgical processes of high strength steel making it difficult to accurately predict the residual stress in laser additive manufacturing, especially for part scale parts. To solve this problem, a multi-scale model considering solid-state phase transformation (SSPT) is proposed to predict thermal, residual stress evolution and distribution for the selective laser melting (SLM) process of high strength tool steel. In 3D finite-element-method thermo-metallurgical-mechanical model, the Kamamoto equation and Koistinen-Marburger equation are used to predict the austenite and martensite phase transformation, respectively. The temperature cycle and thermal behavior are analyzed, and the effects of phase properties transition, transformation-induced volume change and plasticity on residual stress are discussed in detail. The residual stress spatial distribution of multi-layer is obtained. Simulations show that the SSPT has a significant effect on the residual stress evolution in the SLM of high strength steel, considering the influence of phase transformation can effectively reduce tensile residual stress. The thermo-metallurgical-mechanical model is then applied to obtain the inherent strain. The inherent strain method is used to predict the residual stress of the part scale models. Compared with the experimental data, the simulated residual stress shows the same variation trend, which indicates that the proposed multi-scale model can predict residual stress in SLM of high strength steel more accurately and efficiently.

Background Excessive white fat accumulation in humans and other animals is associated with the development of multiple metabolic diseases. It is unknown whether dietary L-arginine supplementation reduces lipid deposition in high fat diet-fed Nile tilapia (Oreochromis niloticus). Results In the present study, we found that dietary supplementation with 1% or 2% arginine decreased the deposition and concentration of fats in the liver; the concentrations of triglycerides, low-density lipoprotein, total cholesterol, and high-density lipoprotein in the serum; and the diameter of adipocytes in intraperitoneal adipose tissue. Compared with the un-supplementation control group, the hepatic activities of alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase, and hepatic concentration of malondialdehyde were reduced but these for catalase and superoxide dismutase were enhanced by dietary supplementation with 2% arginine. Arginine supplementation reduced the total amounts of monounsaturated fatty acids, while increasing the total amounts of n-3 and n-6 polyunsaturated fatty acids in the liver. These effects of arginine were associated with reductions in mRNA levels for genes related to lipogenesis (sterol regulatory element-binding protein-1, acetyl-CoA carboxylase α, stearoyl-CoA desaturase, and fatty acid synthase) but increases in mRNA levels for genes involved in fatty acid β-oxidation (carnitine palmitoyltransferase 1α and peroxisome proliferator-activated receptor α). In addition, hepatic mRNA levels for Δ4 fatty acyl desaturase 2 and elongase 5 of very long-chain fatty acids were enhanced by arginine supplementation. Conclusion These results revealed that dietary L-arginine supplementation to tilapia reduced high fat diet-induced fat deposition and fatty acid composition in the liver by regulating the expression of genes for lipid metabolism.

Lung diseases affect millions of individuals all over the world. Various environmental factors, such as toxins, chemical pollutants, detergents, viruses, bacteria, microbial dysbiosis, and allergens, contribute to the development of respiratory disorders. Exposure to these factors activates stress responses in host cells and disrupt lung homeostasis, therefore leading to dysfunctional epithelial barriers. Despite significant advances in therapeutic treatments for lung diseases in the last two decades, novel interventional targets are imperative, considering the side effects and limited efficacy in patients treated with currently available drugs. Nutrients, such as amino acids (e.g., arginine, glutamine, glycine, proline, taurine, and tryptophan), peptides, and bioactive molecules, have attracted more and more attention due to their abilities to reduce oxidative stress, inhibit apoptosis, and regulate immune responses, thereby improving epithelial barriers. In this review, we summarize recent advances in amino acid metabolism in the lungs, as well as multifaceted functions of amino acids in attenuating inflammatory lung diseases based on data from studies with both human patients and animal models. The underlying mechanisms for the effects of physiological amino acids are likely complex and involve cell signaling, gene expression, and anti-oxidative reactions. The beneficial effects of amino acids are expected to improve the respiratory health and well-being of humans and other animals. Because viruses (e.g., coronavirus) and environmental pollutants (e.g., PM2.5 particles) induce severe damage to the lungs, it is important to determine whether dietary supplementation or intravenous administration of individual functional amino acids (e.g., arginine-HCl, citrulline, N-acetylcysteine, glutamine, glycine, proline and tryptophan) or their combinations to affected subjects may alleviate injury and dysfunction in this vital organ.

Preheating and compression tests of Inconel 718 superalloy double cone specimens were carried out to investigate the microstructure heredity during hot working. Optical microscopy, scanning electron microscopy (SEM), electron backscatter diffraction (EBSD), and transmission electron microscopy (TEM) were used to characterize the microstructure evolution. The results show that intense microstructure heredity can be found at the temperature 960~990 °C. During the preheating process, δ phase precipitation or grain growth could increase the fraction of high angle grain boundary (HAGBs) and Σ3n boundaries. Otherwise, the generation or spread of annealing twin could increase the fraction of LAGBs, Volume fraction of recrystallized grains was evaluated at the whole hot working process. At the temperature of 960~990 °C, the volume fraction of recrystallized grains increases with effective strain increasing. At the super solution temperature of δ phase, the volume fraction of recrystallized grains decreases and then increases with the increase of the effective strain. The unimodal grain size distribution and fully recrystallized grains can be obtained at low strains at 960~990 °C. The twin boundary length fraction of deformed specimens is always lower than that of preheated ones. Discontinuous dynamic recrystallization (DDRX) was considered as the dominant nucleation mechanism, and continuous dynamic recrystallization (CDRX) was strengthened with the increasing grain size. Twin introduced deformation will be the main deformation mode for alloy 718 with larger grain.

Wnt/&beta, catenin is a crucial repressor of adipogenesis. We have shown that E2 promoter binding factor 1 (E2F1) suppresses Wnt/&beta, catenin activity through transactivation of &beta, catenin interacting protein 1 (CTNNBIP1), also known as inhibitor of &beta, catenin and TCF4 (ICAT) in human colorectal cancers. However, it remains unknown whether ICAT is required for E2F1 to promote differentiation by inhibiting &beta, catenin activity in pre-adipocytes. In the present study, we found that 1-methyl-3-isobutylxanthine, dexamethasone, and insulin (MDI)-induced differentiation and lipid accumulation in 3T3-L1 pre-adipocytes was reversed by activation of &beta, catenin triggered by CHIR99021, a GSK3&beta, inhibitor. Intriguingly, we observed a reduced protein level of E2F1 and ICAT at a later stage of pre-adipocytes differentiation. Importantly, overexpression of ICAT in 3T3-L1 pre-adipocytes markedly promote the adipogenesis and partially reversed the inhibitory effect of CHIR99021 on MDI-induced adipogenesis and lipid accumulation by regulating adipogenic regulators and Wnt/&beta, catenin targets. Moreover, pre-adipocytes differentiation induced by MDI were markedly inhibited in siE2F1 or siICAT transfected 3T3-L1 cells. Gene silencing of ICAT in the E2F1 overexpressed adipocytes also inhibited the adipogenesis. These data indicated that E2F1 is a metabolic regulator with an ability to promote pre-adipocyte differentiation by activating ICAT, therefore represses Wnt/&beta, catenin activity in 3T3-L1 cells. We also demonstrated that ICAT overexpression did not affect oleic acid-induced lipid accumulation at the surface of Hela and HepG2 cells. In conclusion, we show that E2F1 is a critical regulator with an ability to promote differentiation and adipogenesis by activating ICAT in pre-adipocytes.

Background Excessive white fat accumulation in humans and other animals is associated with the development of multiple metabolic diseases. It is unknown whether dietary L-arginine supplementation reduces lipid deposition in high fat diet-fed Nile tilapia (Oreochromis niloticus). Results In the present study, we found that dietary supplementation with 1% or 2% arginine decreased the deposition and concentration of fats in the liver; the concentrations of triglycerides, low-density lipoprotein, total cholesterol, and high-density lipoprotein in the serum; and the diameter of adipocytes in intraperitoneal adipose tissue. Compared with the un-supplementation control group, the hepatic activities of alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase, and hepatic concentration of malondialdehyde were reduced but these for catalase and superoxide dismutase were enhanced by dietary supplementation with 2% arginine. Arginine supplementation reduced the total amounts of monounsaturated fatty acids, while increasing the total amounts of n-3 and n-6 polyunsaturated fatty acids in the liver. These effects of arginine were associated with reductions in mRNA levels for genes related to lipogenesis (sterol regulatory element-binding protein-1, acetyl-CoA carboxylase α, stearoyl-CoA desaturase, and fatty acid synthase) but increases in mRNA levels for genes involved in fatty acid β-oxidation (carnitine palmitoyltransferase 1α and peroxisome proliferator-activated receptor α). In addition, hepatic mRNA levels for Δ4 fatty acyl desaturase 2 and elongase 5 of very long-chain fatty acids were enhanced by arginine supplementation. Conclusion These results revealed that dietary L-arginine supplementation to tilapia reduced high fat diet-induced fat deposition and fatty acid composition in the liver by regulating the expression of genes for lipid metabolism.

BACKGROUND Obesity, a major public health problem worldwide, is associated with dysfunction of the intestinal barrier. Glycine (Gly) has been reported to enhance the expression of tight-junction proteins in porcine enterocytes. It is unknown whether Gly can improve intestinal barrier integrity in obese mice. OBJECTIVES This study tested the hypothesis that Gly enhances the intestinal epithelial barrier by regulating endoplasmic reticulum (ER) stress-related signaling and mitigating inflammation in high-fat diet (HFD)-induced obese mice. METHODS Five-week-old male C57BL/6J mice were fed a normal-fat diet (ND; fat = 10% energy) or an HFD (fat = 60% energy) and received drinking water supplemented with 2% Gly or 2.37% l-alanine (Ala; isonitrogenous control) daily for 12 wk. Body weight gain and tissue weights, glucose tolerance and the activation of immune cells, as well as the abundances of tight-junction proteins, ER stress proteins, and apoptosis-related proteins in the jejunum and colon were determined. In addition, the body weights of naive ND and HFD groups (nND and nHFD, respectively) were also recorded for comparison. Differences were analyzed statistically by ANOVA followed by the Duncan multiple-comparison test using SAS software. RESULTS Compared with ND-Ala, HFD-feeding resulted in enhanced macrophage (CD11b+ and F4/80+) infiltration and immune cell activation by 1.9- to 5.4-fold (P

Glycine supplementation has been reported to alleviate lipopolysaccharide (LPS)-induced lung injury in mice. However, the underlying mechanisms responsible for this beneficial effect remain unknown. In the present study, male C57BL/6 mice were treated with aerosolized glycine (1000 mg in 5 mL of 0.9% saline) or vehicle (0.9% saline) once daily for 7 continuous days, and then were exposed to aerosolized LPS (5 mg in 5 mL of 0.9% saline) for 30 min to induce lung injury. Sera and lung tissues were collected 24 h post LPS challenge. Results showed that glycine pretreatment attenuated LPS-induced decreases of mucin at both protein and mRNA levels, reduced LPS-triggered upregulation of pro-inflammatory cytokines, such as tumor necrosis factor-&alpha, (TNF-&alpha, ), interferons, granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukins. Further study showed that glycine-reduced LPS challenge resulted in the upregulation of nuclear factor &kappa, B (NF-&kappa, B), nucleotide binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome. In addition, LPS exposure led to the downregulation of NRF2 and downstream targets, which were significantly improved by glycine administration in the lung tissues. Our findings indicated that glycine pretreatment prevented LPS-induced lung injury by regulating both NLRP3 inflammasome and NRF2 signaling.

3-Acetyldeoxynivalenol (3-Ac-DON), the acetylated derivative of deoxynivalenol (DON), has been reported to be coexisted with DON in various cereal grains. Ingestion of grain-based food products contaminated by 3-Ac-DON might exert deleterious effects on the health of both humans and animals. However, the biological toxicity of 3-Ac-DON on macrophages and the underlying mechanisms remain largely unknown. In the present study, we showed that RAW 264.7 macrophages treated with 0.75 or 1.50 μg/mL of 3-Ac-DON resulted in DNA damage and the related cell cycle arrest at G1 phase and cell death, activation of the ribotoxic stress and the endoplasmic reticulum (ER) stress responses. The 3-Ac-DON-induced cell death was accompanied by a protective autophagy, because the gene silencing of Atg5 using the small interfering RNA enhanced cell death. Results of further experiments revealed a role for lysosomal membrane permeabilization in the 3-Ac-DON triggered inhibition of autophagic flux. Additional work also showed that increased lysosomal biogenesis and leakage of cathepsin B (CTSB) from lysosomes to cytosol was critical for the 3-Ac-DON-induced cell death. Importantly, 3-Ac-DON-induced DNA damage and cell death were rescued by CA-074-me, a CTSB inhibitor. Collectively, these results indicated a critical role of lysosomal membrane permeabilization in the 3-Ac-DON-induced apoptosis of RAW 264.7 macrophages.

Inflammation and oxidative stress play key roles in the process of aging and age-related diseases. Since serine availability plays important roles in the support of antioxidant and anti-inflammatory defense system, we explored whether serine deficiency affects inflammatory and oxidative status in D-galactose-induced aging mice. Male mice were randomly assigned into four groups: mice fed a basal diet, mice fed a serine- and glycine-deficient (SGD) diet, mice injected with D-galactose and fed a basal diet, and mice injected with D-galactose and fed an SGD diet. The results showed that D-galactose resulted in oxidative and inflammatory responses, while serine deficiency alone showed no such effects. However, serine deficiency significantly exacerbated oxidative stress and inflammation in D-galactose-treated mice. The composition of fecal microbiota was affected by D-galactose injection, which was characterized by decreased microbiota diversity and downregulated ratio of Firmicutes/Bacteroidetes, as well as decreased proportion of Clostridium XIVa. Furthermore, serine deficiency exacerbated these changes. Additionally, serine deficiency in combination with D-galactose injection significantly decreased fecal butyric acid content and gene expression of short-chain fatty acid transporters (Slc16a3 and Slc16a7) and receptor (Gpr109a) in the brain. Finally, serine deficiency exacerbated the decrease of expression of phosphorylated AMPK and the increase of expression of phosphorylated NFκB p65, which were caused by D-galactose injection. In conclusion, our results suggested that serine deficiency exacerbated inflammation and oxidative stress in D-galactose-induced aging mice. The involved mechanisms might be partially attributed to the changes in the microbiota-gut-brain axis affected by serine deficiency.

Nonthermal plasma has a great potential for the partial oxidation of gasoline to form cleaner fuels. However, the formation of deep oxidation products and cracking products makes plasma environmentally unfriendly. This paper reports the partial oxidation of simulated gasoline (n-C5H12) to syngas and oxygenated products. For this purpose, a dielectric barrier discharge reactor was used in which the background temperature and gas pressure could be individually controlled. We found that the conversion of n-C5H12 increased with increasing background temperature until 498 K, then reduced at 523 K because of the resistive loss of discharge power. In contrast, the selectivity of oxygenates and the H2/CO value monotonously decreased with increasing background temperature. It was inferred that the conversion of n-C5H12 depends on both the thermo-chemistry and the electron-induced chemistry, and their contribution to this process was almost the same at 498 K. In contrast, the mechanism of product formation was mainly controlled by thermo-chemistry. The benefits of using cold plasma to simultaneously produce syngas and oxygenates were highlighted. Our results may be used to develop a new concept for designing an environmentally friendly plasma reformer.

Glycine supplementation has been reported to enhance white-fat loss and improve sensitivity to insulin in animals with obesity or type 2 diabetes. However, the underlying mechanisms responsible for the beneficial effects of glycine remain largely unknown. The purpose of this study was to test the hypothesis that glycine regulates adipocyte differentiation, adipogenesis, and lipolysis, therefore, contributing to white-fat reduction. 3T3-L1 pre-adipocytes were induced to differentiate into adipocytes in the presence of glycine (0, 0.25, 1.0, and 2.0 mmol/L) or resveratrol (50 or 100 μmol/L, served as a positive control) during the differentiation process. Hela and HepG2 cells cultured with oleic acid to induce lipid accumulation in the presence of glycine (0, 1.0, and 2.0 mmol/L) or 10 μmol/L isoproterenol (served as a positive control) for 24 h. Intracellular lipid accumulation, intracellular triglycerides, lipid droplets’ diameters of mature adipocytes, mRNA, and protein levels of genes involved in the adipogenesis and lipolysis were analyzed. Isobutylxanthine–dexamethasone–insulin (MDI)-induced adipogenesis in 3T3-L1 cells were blocked by resveratrol, but not by glycine, as shown by decreased lipid contents, reduced diameters of lipid droplets, decreased protein abundances for peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer-binding protein α (C/EBPα), as well as increased protein abundance of peroxisome proliferator-activated receptor coactivator-1α (PGC-1α), critical transcriptional factors that regulates adipogenesis. However, the mRNA levels of adiponectin and interleukin-10 (IL-10), two adipose-derived adipocytokines with anti-inflammatory effects, were greatly enhanced (P

Ultrasonic impact treatment (UIT) is an effective method that has been widely applied in welding structure to improve the fatigue properties of materials. It combines mechanical impact and ultrasonic vibration to produce plastic deformation on the weld joints surface, which introduces beneficial compressive residual stress distribution. To evaluate the effect of UIT technology on alleviating the residual stress of welded joints, a novel numerical analysis method based on the inherent strain theory is proposed to simulate the stress superposition of welding and subsequent UIT process of 304 stainless steel. Meanwhile, the experiment according to the process was carried out to verify the simulation of residual stress values before and after UIT. By the results, optimization of UIT application could effectively reduce the residual stress concentration after welding process. Residual tensile stress of welded joints after UIT is transformed into residual compressive stress. UIT formed a residual compressive stress layer with a thickness of about 0.13 mm on the plate. The numerical simulation results are consistent with the experimental results. The work in this paper could provide theoretical basis and technical support for the reasonable evaluation of the ultrasonic impact on residual stress elimination and mechanical properties improvement of welded joints.

Bi-stable fluidic amplifier containing no moving parts was used for switching fluid flow passing through it into an actuator in a liquid-jet hammer. So far, there has been no design basis for developing a liquid-jet hammer with high performance. To provide a guidance, this paper elaborates on the computational fluid dynamics simulation method for investigating the effect of actuator parameters on the performance of a liquid-jet hammer associated with its jet behavior. Given that couple mechanism exists between the flow field in the bi-stable fluidic amplifier and the actuator, dynamic mesh technique and a user-defined function written in C programming language were used to update the mesh in the simulations. Two evaluation criteria—pressure recovery and flux utilization ratio—for a liquid-jet hammer were used in this study. Experimental tests were conducted to verify the simulation results, by which the accuracy and reliability of this computational fluid dynamics simulation method was proved. Besides, comprehensive analysis of the flow behavior in the fluidic amplifier of a liquid-jet hammer was performed by the use of computational fluid dynamics visualization method.

Background Liver dysfunction impairs immunological homeostasis. Glycine (Gly) has been reported to have antioxidative and anti-inflammatory effects and to regulate apoptosis in various models. Objectives The aim of the present study was to determine whether Gly could attenuate LPS-induced liver injury. Methods In Experiment 1, 48 6-week-old male C57BL/6 mice were randomly assigned into one of 4 groups: CON (control), GLY [orally administered Gly, 5 g · kg body weight (BW)-1 · d-1 for 6 d], LPS (5 mg/kg BW, intraperitoneally administered), and GLY + LPS (Gly supplementation, and on day 7 LPS treatment). In Experiment 2, mice were untreated, pretreated with Gly as above, or pretreated with Gly + l-buthionine sulfoximine (BSO) (0.5 g/kg BW, intraperitoneally administered every other day) for 6 d. On day 7, mice were injected with LPS as above. Histological alterations, activities of antioxidative enzymes, apoptosis, and immune cell infiltration were analyzed. Results In Experiment 1, compared with CON, LPS administration resulted in increased karyolysis and karyopyknosis in the liver by 8- to 10-fold, enhanced serum activities of alanine transaminase (ALT), aspartate transaminase (AST), and lactate dehydrogenase (LDH) by 1- to 1.8-fold, and increased hepatic apoptosis by 5.5-fold. Furthermore, LPS exposure resulted in increased infiltration of macrophages and neutrophils in the liver by 3.2- to 7.5-fold, elevated hepatic concentrations of malondialdehyde and hydrogen peroxide (H2O2), and elevated myeloperoxidase (MPO) activity by 1.5- to 6.3-fold. In Experiment 2, compared with the LPS group, mice in the GLY + LPS group had fewer histological alterations (68.5%-75.9%); lower serum ALT, AST, and LDH activities (24.3%-64.7%); and lower hepatic malondialdehyde and H2O2 concentrations (46.1%-80.2%), lower MPO activity (39.2%), immune cell infiltration (52.3%-85.3%), and apoptosis (69.6%), which were abrogated by BSO. Compared with the GLY + LPS group, mice in the GLY + BSO + LPS group had lower hepatic activities of catalase, superoxide dismutase, and glutathione peroxidase by 33.5%-48.5%; increased activation of NF-κB by 2.3-fold; and impaired nuclear factor (erythroid-derived 2)-like 2 signaling by 38.9%. Conclusions Gly is a functional amino acid with an ability to protect the liver against LPS-induced injury in mice.

l-Tryptophan (Trp) is known to play an important role in the health of the large intestine. However, a role of dietary Trp in the small-intestinal mucosal barrier and microbiota remains poorly understood. The present study was conducted with weaned piglets to address this issue. Postweaning piglets were fed for 4 weeks a corn- and soybean meal-based diet supplemented with 0 (Control), 0.1, 0.2, or 0.4% Trp. The small-intestinal microbiota and serum amino acids were analyzed by bacterial 16S rRNA gene-based high-throughput sequencing methods and high-performance liquid chromatography, respectively. The mRNA levels for genes involved in host defense and the abundances of tight-junction proteins in jejunum and duodenum were measured by real time-PCR and Western blot techniques, respectively. The concentrations of Trp in the serum of Trp-supplemented piglets increased in a dose-dependent manner. Compared with the control group, dietary supplementation with 0.2&ndash, 0.4% Trp reduced the abundances of Clostridium sensu stricto and Streptococcus in the jejunum, increased the abundances of Lactobacillus and Clostridium XI (two species of bacteria that can metabolize Trp) in the jejunum, and augmented the concentrations of secretory immunoglobulin A (sIgA) as well as mRNA levels for porcine &beta, defensins 2 and 3 in jejunal tissues. Moreover, dietary Trp supplementation activated the mammalian target of rapamycin signaling and increased the abundances of tight-junction proteins (zonula occludens (ZO)-1, ZO-3, and claudin-1) in jejunum and duodenum. We suggested that Trp-metabolizing bacteria in the small intestine of weaned pigs primarily mediated the beneficial effects of dietary Trp on its mucosal integrity, health, and function.

Apoptosis of intestinal epithelial cells following oxidative stress is a major cause of mucosal barrier dysfunction and is associated with the pathogenesis of various gastrointestinal diseases. Although L-tryptophan (Trp) is known to improve intestinal integrity and function, a beneficial effect of N-acetyl serotonin (NAS), a metabolite of Trp, on the apoptosis of enterocytes and the underlying mechanisms remain largely unknown. In the present study, we showed that porcine enterocytes treated with 4-hydroxy-2-nonenal (4-HNE), a metabolite of lipid peroxidation, led to upregulation of apoptotic proteins, including Bax and cleaved caspase-3, and reduction of tight junction proteins. These effects of 4-HNE were significantly abrogated by NAS. In addition, NAS reduced ROS accumulation while increasing the intracellular concentration of glutathione (GSH), and the abundance of the Nrf2 protein in the nucleus and its downstream target proteins. Importantly, these protective effects of NAS were abrogated by Atra, an inhibitor of Nrf2, indicating a dependence on Nrf2 signaling. Taken together, we demonstrated that NAS attenuated oxidative stress-induced cellular injury in porcine enterocytes by regulating Nrf2 signaling. These findings provide new insights into a functional role of NAS in maintaining intestinal homeostasis.

With considering the latent heat of melting and the temperature-dependent thermo-physical properties, a Gauss body heat source is employed to analyze the temperature field and the morphology of molten pool with a single-track and multi-track scan strategy in Substrate-Powder (SP) model, Full-Powder (FP) model and Partial-Solid model (PS), respectively. It is shown that the maximum temperature (Tmax) and maximum cooling rate (vcmax) of single-track increase with preheating temperature, while the maximum heating rate (vhmax) presenting an opposite trend. The preheating temperature has the greatest influence on the length and depth of the molten pool of SP model and the width of FP model. For the reason of heat accumulation, the Tmax of each track increases with the decrease of solid volume in the model and increases with the number of scan tracks in a multi-track scan strategy. Due to prominent thermal conductivity of SP model, heat accumulation of multi-track scanning has the smallest effect on the size of pool, but it drives the molten pool length of PS model and FP model increasing seriously. The verification experiment of SP model was in good agreement with the simulation results, proved that numerical simulation is capable of predicting the temperature field and molten pool morphology during the SLM process.

Glycine supplementation has been reported to enhance white-fat loss and improve sensitivity to insulin in animals with obesity or type 2 diabetes. However, the underlying mechanisms responsible for the beneficial effects of glycine remain largely unknown. The purpose of this study was to test the hypothesis that glycine regulates adipocyte differentiation, adipogenesis, and lipolysis, therefore, contributing to white-fat reduction. 3T3-L1 pre-adipocytes were induced to differentiate into adipocytes in the presence of glycine (0, 0.25, 1.0, and 2.0 mmol/L) or resveratrol (50 or 100 μmol/L, served as a positive control) during the differentiation process. Hela and HepG2 cells cultured with oleic acid to induce lipid accumulation in the presence of glycine (0, 1.0, and 2.0 mmol/L) or 10 μmol/L isoproterenol (served as a positive control) for 24 h. Intracellular lipid accumulation, intracellular triglycerides, lipid droplets' diameters of mature adipocytes, mRNA, and protein levels of genes involved in the adipogenesis and lipolysis were analyzed. Isobutylxanthine-dexamethasone-insulin (MDI)-induced adipogenesis in 3T3-L1 cells were blocked by resveratrol, but not by glycine, as shown by decreased lipid contents, reduced diameters of lipid droplets, decreased protein abundances for peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer-binding protein α (C/EBPα), as well as increased protein abundance of peroxisome proliferator-activated receptor coactivator-1α (PGC-1α), critical transcriptional factors that regulates adipogenesis. However, the mRNA levels of adiponectin and interleukin-10 (IL-10), two adipose-derived adipocytokines with anti-inflammatory effects, were greatly enhanced (P 0.05) by 2 mmol/L glycine. Compared with non-treated controls, 10 μmol/L isoproterenol significantly decreased (P 0.05) the intracellular lipid and triglyceride contents induced by oleic acid in Hela and HepG2 cells. mRNA level of fatty acid synthase (FASN), a gene involved in fatty acid synthesis, was significantly reduced (P 0.05), while that for ATGL (adipose triglyceride lipase) and HSL (hormone-sensitive lipase), genes involved in lipolysis were significantly enhanced (P 0.05) by isoproterenol. However, oleic acid induced the accumulation of intracellular triglyceride and lipid contents were not affected by glycine. In conclusion, glycine exposure enhanced the mRNA levels of adipose-derived adiponectin and IL-10 without affecting adipogenesis and lipolysis in 3T3-L1 adipocytes. These findings provide a possible explanation for the anti-obesity and anti-diabetic effects of glycine that were previously reported in animal models. More studies are needed to uncover the underlying mechanisms responsible for this regulatory effect of glycine on anti-inflammatory adipocytokines expression in both in vitro and in vivo models.

n-3 Long-chain PUFA up-regulate intestinal lipid metabolism. However, whether these metabolic effects of PUFA on intestine are mediated by AMP-activated protein kinase (AMPK) remains to be elucidated. To determine the effects ofα-linolenic acid (ALA) on intestinal fatty acid (FA) metabolism and whether these effects were affected by AMPK deletion, mice deficient in the catalytic subunit of AMPKα1 or AMPKα2 and wild-type (WT) mice were fed either a high-fat diet (HF) or HF supplemented with ALA (HF-A). The results showed that ALA supplementation decreased serum TAG content in WT mice. ALA also increased mRNA expression of genes (carnitine palmitoyltransferase 1a, acyl-CoA oxidase 1, medium-chain acyl-CoA dehydrogenase, cytochrome P450 4A10 and pyruvate dehydrogenase kinase isoenzyme 4a) involved in intestinal lipid oxidation and mRNA expression of TAG synthesis-related genes (monoacylglycerolO-acyltransferase 2, diacylglycerolO-acyltransferases 1 and 2) in WT mice. Consistent with these, expression levels of phosphorylated AMPKα1 and AMPKα2 were also increased in WT mice after ALA addition. However, in the absence of either AMPKα1 or AMPKα2, ALA supplementation failed to increase intestinal lipid oxidation. In addition, no significant effects of either diet (HF and HF-A) or genotype (WT, AMPKα1–/–and AMPKα2–/–) on FA uptake in the intestine and faecal TAG output were observed. Our results suggest that AMPK is indispensable for the effects of ALA on intestinal lipid oxidation.

Fat Mass and Obesity-associated protein (FTO), associated with obesity, is proved to demethylate N6-methyladenosine (m 6 A), which raises questions regarding whether m 6 A plays vital roles in adipogenesis. To prove this, overexpression and knockdown of FTO and METTL3, as well as the chemical treatment in procine adipocytes were conducted. The results showed FTO negatively regulated m 6 A levels and positively regulated adipogenesis, while METTL3 positively correlated with m 6 A levels and negatively with adipogenesis. To remove the potential effect of FTO and METTL3 gene, chemical reagents of methylation inhibitor cycloleucine and methyl donor betaine were used to test the regulation effect of m 6 A on adipogenesis. The results showed the inverse effect of m 6 A on lipid accumulation in porcine adipocytes. These findings provide compelling evidence that m 6 A plays a critical role in the regulation of adipogenesis.