Metabolic disorders are highly prevalent in modern society. Exercise mimetics are defined as pharmacologic compounds that can produce the beneficial effects of fitness. Recently, there has been increased interest in the role of eugenol and transient receptor potential vanilloid 1 (TRPV1) in improving metabolic health. The aim of this study was to investigate whether eugenol acts as an exercise mimetic by activating TRPV1. Here, we showed that eugenol improved endurance capacity, caused the conversion of fast to slow muscle fibers, and promoted white fat browning and lipolysis in mice. Mechanistically, eugenol promoted muscle fiber type transformation by activating TRPV1-mediated CaN signaling pathway. Subsequently, we identified IL-15 as a myokine that is regulated by the CaN/Nuclear factor of activated T cells cytoplasmic 1 (NFATc1) signaling pathway. Moreover, we found that TRPV1-mediated CaN/NFATc1 signaling, activated by eugenol, controlled IL-15 levels in C2C12 myotubes. Our results suggest that eugenol may act as an exercise mimetic to improve metabolic health via activating the TRPV1-mediated CaN signaling pathway.
Abstract Background Starch is a major component of carbohydrates and a major source of energy for monogastric animals. Starch is composed of amylose and amylopectin and has different physiological functions due to its different configuration and structure. It has been shown that the energy supply efficiency of amylose is lower than that of amylopectin. However, there are few studies on the effect of starch structure on the available energy of pigs. The purpose of this study was to measure the effect of different structures of starch in the diet on the net energy (NE) of pigs using a comparative slaughter method and to establish a prediction equation to estimate the NE of starch with different structures. A total of fifty-six barrows (initial body weight 10.18 ± 0.11kg) were used, and they were housed and fed individually. Pigs were divided into 7 treatments according to their weight, with 8 replicates for each treatment and 1 pig for each replicate. One of the treatments was randomly selected as the initial slaughter group (ISG). Pigs in the remaining groups were assigned to 6 dietary treatment and slaughtered at the conclusion of the experiment. The basic diet contains corn, soybean meal, without additional starch. The other five starch experimental groups were fed semi-pure diets with amylose/amylopectin ratios (AR) of 3.09, 1.47, 0.25, 0.15 and 0.12, respectively. The diets and water were provided ad libitum for 28 d. Results Results showed that compared with the high amylose (AM) groups (AR 3.09 and 1.47), the high amylopectin (AP) group (AR 0.15) significantly increased the final BW, average daily weight gain and average daily feed intake of pigs (quadratic, P < 0.01), but the F: G of the high amylose group was lower (quadratic, P < 0.05). In addition, the high amylopectin groups (AR 0.15 and 0.12) has higher (quadratic, P < 0.001) nutrient digestibility of dry matter, crude protein, gross energy and crude ash. Meanwhile, compared with other groups AR 0.15 group has a higher NE intake and energy retention (RE), while AR 3.09 group has the lowest NE intake and RE (linear, P < 0.05). The regressive equation for predicting with starch structures was established as RE = 1235.243-48.298AM/AP ( r 2= 0.657, P = 0.05). Conclusions In conclusion, with the increase of dietary amylopectin content, NE intake and RE of pigs were increased, indicating that diets high in amylopectin were more conducive to promoting the growth of pigs in the late conservation period.
Abstract Age-related changes to the epigenome are well-documented, especially the pattern of genome-wide DNA methylation (DNAm) changes observed in blood. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by the age-related acquisition and expansion of leukemogenic mutations in hematopoietic stem cells (HSCs), is associated with blood cancer and coronary artery disease (CAD). Epigenetic regulators DNMT3A and TET2 are the two most frequently mutated CHIP genes. Here, we present results from an epigenome-wide association study for CHIP in 582 Cardiovascular Health Study participants, with replication in 2655 Atherosclerosis Risk in Communities Study participants. We show that DNMT3A and TET2 CHIP have distinct and directionally opposing genome-wide DNAm association patterns consistent with their regulatory roles, albeit both promoting self-renewal of HSCs. Mendelian randomization analyses indicate that a subset of DNAm alterations for these two leading CHIP genes may promote the risk for CAD.
A feeding trial for 91 days was conducted to investigate effects of active immunization against porcine Sox6 (pSox6) on meat quality and myosin heavy chain (MyHC) isoform expression in growing-finishing pigs. Twenty-four castrated Duroc × Landrace × Yarkshire pigs were randomly divided into three groups: (1) Control group; (2) 1 mg/head pSox6 active immunity group; (3) 4 mg/head pSox6 active immunity group (4 mg/head group). The results showed that pigs in 4 mg/head group had a greater a* (Redness) and a higher marbling score, while no significant effect was observed in L* (Lightness), b* (Yellowness), intramuscular fat and cooking loss. Muscle succinic dehydrogenase activity in pSox6 active immunization groups was significantly increased, and muscle lactate dehydrogenase activity was significantly reduced. Meanwhile, active immunization against pSox6 upregulated the mRNA expression of MyHC I, while no effect was observed on the mRNA expressions of MyHC IIa, MyHC IIx, MyHC IIb. In addition, pigs in the 4 mg/head group exhibited lower Sox6 mRNA level and higher MyHC I protein level, while no significant influence was observed on MyHC IIb protein level. Together, our data imply that active immunization against pSox6 could improve the pork quality and promote the MyHC I expression in growing-finishing pigs.
This experiment was conducted to explore the effects of gut microbiota on neonatal diarrhea in a germ-free (GF) pig model. Twelve hysterectomy-derived GF piglets were housed in six sterile isolators. Among them, six piglets were treated as the GF group, and the other six piglets were orally introduced with healthy sow fecal suspension and regarded as the fecal microbiota transplantation (FMT) group. Another six piglets from natural birth were considered as the conventional (CV) group. The GF and FMT piglets were hand-fed with sterile milk powder for 21 days, and the CV piglets were suckled for the same days. Then, all piglets were fed with sterile feed for another 21 days. Results exhibited that the GF group’s fecal score and moisture level were higher than those in the CV and FMT groups (p < 0.05). Meanwhile, the abundances of colonic AQP1 and AQP8 in the GF group were the greatest among these treatments (p < 0.05). However, FMT piglets had a lower fecal score in d 22–28 and d 29–35 than that in the CV piglets (p < 0.05). Collectively, the absence of gut microbiota may cause diarrhea in the piglet model, and transplantation of maternal fecal microbiota may reverse it.
Abstract Background Lentinan (LNT) may regulate many important physiological functions of human and animals. This study aimed to verify whether LNT administration could relieve diarrhea via improving gut immunity in rotavirus (RV)-challenged weaned pigs. Methods Twenty-eight weaned pigs were randomly fed 2 diets containing 0 or 84 mg/kg LNT product for 19 d ( n = 14). RV infection was executed on d 15. After extracting polysaccharides from LNT product, its major monosaccharides were analyzed. Then, LNT polysaccharide was used to administrate RV-infected IPEC-J2 cells. Results Dietary LNT supplementation supported normal function of piglets even when infected with RV, as reflected by reduced growth performance loss and diarrhea prevalence, and maintained gut immunity ( P < 0.05). The polysaccharide was isolated from LNT product, which molecular weight was 5303 Da, and major monosaccharides included glucose, arabinose and galactose. In RV-infected IPEC-J2 cells, this polysaccharide significantly increased cell viability ( P < 0.05), and significantly increased anti-virus immunity via regulating pattern recognition receptors and host defense peptides ( P < 0.05). Conclusion Those results suggest that LNT administration increases the piglets’ resistance to RV-induced stress, likely by supporting intestinal immunity.
The objective of this study was to investigate the effects of dietary L-theanine (LTH) supplementation on finishing pigs' antioxidant capacity and lipid metabolism. Results showed that dietary LTH supplementation increased the activity of antioxidant enzymes and decreased the content of malondialdehyde in serum, longissimus dorsi muscle (LD muscle), and liver of finishing pigs (P < 0.05). Dietary LTH supplementation decreased serum low-density lipoprotein cholesterol content and increased high-density lipoprotein cholesterol content (P < 0.05). Moreover, LTH-containing diet decreased the contents of triglyceride and total cholesterol in serum, LD muscle, and liver (P < 0.05). In liver and LD muscle, LTH activated Nrf2-Keap1 signaling pathway, increased mRNA expression levels of genes related to lipolysis and fatty acid oxidation and reduced the expression levels of genes related to adipogenesis (P < 0.05). According to our study, nutritional supplementation with LTH enhanced finishing pigs' antioxidant capacity and lipid metabolism.
Computation offloading is a key technique to enhance the performance and interactivity of mobile application through migrating the computation-intensive tasks to the cloud. However, efficient offloading is challenging in practice in that a mobile application often consists of computation tasks that have dependency with execution order constraints as well as parallel tasks that can be executed non-deterministically. In addition, each mobile device executes its application as a separate process, and performs asynchronous communication with cloud environment with heterogeneous computing and storage resource that are shared among mobile devices. In this paper, we propose a collaborative asynchronous computation offloading framework to improve the interactivity and execution efficiency of mobile applications. Initially, each mobile application calculates its local offloading plan. At runtime, it follows the offloading plan for task execution and requests the offloading computation from the cloud system. Upon receiving the request, cloud system performs dynamic adjustment of the offloading request according to the cloud runtime status. We implement our proposed offloading framework. The evaluation on 11 real-world mobile applications demonstrates its effectiveness.
Supplementary Methods, Figures 1-3 from c-Jun Protects Hypoxia-Inducible Factor-1α from Degradation via Its Oxygen-Dependent Degradation Domain in a Nontranscriptional Manner
This study aimed to investigate the effects of chronic exposure to low levels of dietary aflatoxin B1 (AFB1) on growth performance, apparent total tract digestibility and intestinal health in pigs. In a 102-day experiment, fourteen barrows (Duroc×Landrace×Yorkshire, initial BW = 38.21 ± 0.45 kg) were randomly divided into control (CON, basal diet) and AFB1 groups (the basal diet supplemented with 280 μg/kg AFB1). Results revealed that the AFB1 exposure decreased the final BW, ADFI and ADG in pigs (p < 0.10). AFB1 exposure also decreased the apparent total tract digestibility of dry mater and gross energy at 50 to 75 kg and 105 to 135 kg stages, and decreased the apparent total tract digestibility of ether extract at 75 to 105 kg stage (p < 0.05). Meanwhile, AFB1 exposure increased serum diamine oxidase activity and reduced the mRNA abundance of sodium-glucose cotransporter 1, solute carrier family 7 member 1 and zonula occluden-1 in the jejunal mucosa (p < 0.05). Furthermore, AFB1 exposure decreased superoxide dismutase activity (p < 0.05) and increased 8-hydroxy-2'-deoxyguanosine content (p < 0.10) in jejunal mucosa. AFB1 exposure also increased tumor necrosis factor-α, interleukin-1β and transforming growth factor-β mRNA abundance in jejunal mucosa and upregulated Escherichia coli population in colon (p < 0.05). The data indicated that chronic exposure to low levels of dietary AFB1 suppressed growth performance, reduced the apparent total tract digestibility and damaged intestinal barrier integrity in pigs, which could be associated with the decreased intestinal antioxidant capacity and the increased pro-inflammatory cytokine production.