The effects of dietary fiber level on nutrient digestibility in growing pigs

The objective of this study was to investigate the effects of total dietary fiber level on nutrient digestibility and the relationship between apparent total tract digestibility of total dietary fiber, and soluble dietary fiber, insoluble dietary fiber and available energy. Sugar beet pulp was as the only fiber source. The experiment was designed as a 6 × 6 Latin square with an adaptation period of 7 d followed by a 5-d total collection of feces and urine. Feed intake tended to decrease (P =0.10) as total dietary fiber level increased. The apparent total tract digestibility of dry matter, crude protein and gross energy decreased (P <0.01) when total dietary fiber increased but the digestibility of soluble dietary fiber and insoluble dietary fiber increased (P <0.01). The digestible energy and metabolizable energy content of diets decreased (P <0.01) as the total dietary fiber increased

Heterogeneous ice nucleation correlates with bulk-like interfacial water

Establishing a direct correlation between interfacial water and heterogeneous ice nucleation (HIN) is essential for understanding the mechanism of ice nucleation. Here, we study the HIN efficiency of polyvinyl alcohol (PVA) surfaces with different densities of hydroxyl groups. We find that the HIN efficiency increases with the decrease of the hydroxyl group density. By explicitly considering that interfacial water molecules of PVA films consist of ‘tightly bound water’, ‘bound water’ and ‘bulk-like water’, we reveal that ‘bulk-like water’ can be correlated directly to the HIN efficiency of surfaces. As the density of hydroxyl groups decreases, ‘bulk-like water’ molecules can rearrange themselves with a reduced energy barrier into ice due to the diminishing constraint by the hydroxyl groups on the PVA surface. Our study not only provides a new strategy on experimentally controlling HIN efficiency but also gives another perspective in understanding the mechanism of ice nucleation, i.e., the phase change efficiency of ‘bulk-like’ interfacial water of a film is a predictor for the HIN efficiency of that film

Karonudib is a promising anticancer therapy in hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) is the most common form of liver cancer and is generally caused by viral infections or consumption of mutagens, such as alcohol. While liver transplantation and hepatectomy is curative for some patients, many relapse into disease with few treatment options such as tyrosine kinase inhibitors, for example, sorafenib or lenvatinib. The need for novel systemic treatment approaches is urgent. Methods: MTH1 expression profile was first analyzed in a HCC database and MTH1 mRNA/protein level was determined in resected HCC and paired paracancerous tissues with polymerase chain reaction (PCR) and immunohistochemistry. HCC cancer cell lines were exposed in vitro to MTH1 inhibitors or depleted of MTH1 by siRNA. 8-oxoG was measured by the modified comet assay. The effect of MTH1 inhibition on tumor growth was explored in HCC xenograft in vivo models. Results: MTH1 protein level is elevated in HCC tissue compared with paracancerous liver tissue and indicates poor prognosis. The MTH1 inhibitor Karonudib (TH1579) and siRNA effectively introduce toxic oxidized nucleotides into DNA, 8-oxoG, and kill HCC cell lines in vitro. Furthermore, we demonstrate that HCC growth in a xenograft mouse model in vivo is efficiently suppressed by Karonudib. Conclusion: Altogether, these data suggest HCC relies on MTH1 for survival, which can be targeted and may open up a novel treatment option for HCC in the future

Integrative Analysis of Energy Partition Patterns and Plasma Metabolomics Profiles of Modern Growing Pigs Raised at Different Ambient Temperatures

This study explores the energy partition patterns of modern growing pigs at 25 kg and 65 kg raised at gradient-ambient temperatures. It also investigates the underlying changes in plasma under such conditions, based on the integrative analysis of indirect calorimetry and non-target metabolomics profiling. Thirty-six barrows with initial BW of 26.4 ± 1.9 kg and 24 barrows with initial BW of 64.2 ± 3.1 kg were successively allotted to six respiration chambers with ambient temperatures set as 18 °C, 21 °C, 23 °C, 27 °C, 30 °C, and 32 °C, and four respiration chambers with ambient temperatures set as 18 °C, 23 °C, 27 °C, and 32 °C, respectively. Each pig was kept in an individual metabolic crate and consumed feed ad libitum, then transferred into the respiration chamber after a 7-day adaptation period for 5-day indirect calorimetry assay and 1-day fasting. As the ambient temperature increased from 18 °C to 32 °C, the voluntary feed intake, metabolizable energy intake, nitrogen intake, and retention, total heat production, and energy retention as a protein of growing pigs at 25 kg and 65 kg all linearly decreased (p &lt; 0.05), with greater coefficients of variation for pigs at 65 kg when temperatures changed from 18 °C to 32 °C. The cortisol and thyroid hormone levels in the plasma of 25 kg pigs linearly decreased as the ambient temperature increased from 18 °C to 32 °C (p &lt; 0.05), and 13 compounds were identified through metabolomics analysis, including up-regulated metabolites involved in fatty acid metabolism, such as adrenic acid and down-regulated metabolites involved in amino acid metabolism, such as spermidine at 32 °C. These results suggested that modern growing pigs at heavier bodyweight were more sensitive to high temperatures on energy intake and partition. Most of the identified metabolites altered at high ambient temperatures are associated with suppressed fatty acid oxidation and elevated lipogenesis and protein degradation.</jats:p

Energy partition patterns and plasma metabolomics profiles of modern growing pigs under different ambient temperatures: modelling and integrative analysis

Abstract Background Most of the studies focusing on energy partition patterns of growing pigs and the related mechanisms under different ambient temperatures were carried out during 1970s to early 2000s. With the rapid developments in pig breeding, research updates on such topics concerning modern growing pigs have been absent in the last decade. This study developed mathematical models to predict the energy partition patterns of modern growing pigs with different BWs at gradient-ambient temperatures, and investigated the underlying changes in plasma under such conditions based on the integrative analysis of indirect calorimetry and non-target metabolomics profiling. Methods In trial 1, 36 barrows with initial BW of 26.4 ± 1.9 kg were allotted to a 6 × 6 Latin Square Design with ambient temperatures set as 18 °C, 21 °C, 23 °C, 27 °C, 30 °C, and 32 °C. In trial 2, 24 barrows with initial BW of 64.2 ± 3.1 kg were allotted to a 4 × 6 Youden Square Design with ambient temperatures set as 18 °C, 23 °C, 27 °C, and 32 °C. Each pig was kept in individual metabolic crate and consumed feed ad libitum, then transferred into the respiration chamber for 5-day indirect calorimetry assay and 1-day fasting. The energy and nitrogen balance as well as energy utilization efficiency were determined, and mathematical models were developed to predict the voluntary feed intake (VFI), metabolizable energy intake (MEi) and energy retention as protein (REP) and lipid (REL) using BW and ambient temperature (T) as predictors. Moreover, plasma samples were collected from pigs at 25 kg under different temperatures, and the levels of hormone and metabolites in plasma were determined using biochemical and the metabolomics approaches, respectively. Results As the ambient temperature increased from 18 °C to 32 °C, the VFI, MEi, N intake and retention, total heat production (THP) and REP of growing pigs at 25 kg all linearly decreased (P &lt; 0.05). There were interaction effects between BW and T on VFI, MEi, N balance, adjusted THP, REP and REL (P &lt; 0.05). Parallel curves were observed between the VFI model developed in the current study and that built previously, but our MEi model showed discrepancy from the previous model especially at high temperatures. The models simulated for REP and REL are: REP (kJ/kg BW0.6/d) = -233.38–67.28 × BW0.6 + 3.16 × (BW0.6)2 + 39.58 × T – 0.76 × T2 – 0.26 × BW0.6 × T + 0.26 × MEi, and REL (kJ/kg BW0.6/d) = -465.10 + 8.10 × BW0.6 – 1.03 × (BW0.6)2 – 53.73 × T + 1.34 × T2 + 0.67 × BW0.6 × T + 0.69 × MEi, respectively. The cortisol and thyroid hormone levels in plasma linearly decreased as the ambient temperature increased from 18 °C to 32 °C, and 13 compounds were identified through metabolomics analysis, including up-regulated metabolites involved in fatty acid metabolism such as adrenic acid and down-regulated metabolites involved in amino acid metabolism such as spermidine at 32 °C. Conclusion These results suggested that pigs at heavier body weight were more sensitive to high temperatures on energy intake and partition, and pigs with modern genotypes could be more sensitive to heat stress than pigs with older genotypes. Most of the identified metabolites altered under high ambient temperatures are associated with suppressed fatty acid oxidation and elevated lipogenesis and protein degradation.</jats:p