Effects of microbe-derived antioxidants on growth performance, hepatic oxidative stress, mitochondrial function and cell apoptosis in weaning piglets.

BACKGROUND: Weaning causes redox dyshomeostasis in piglets, which leads to hepatic oxidative damage. Microbe-derived antioxidants (MA) have great potential for anti-oxidation. This study aimed to investigate changes in hepatic redox system, mitochondrial function and apoptosis after weaning, and effects of MA on growth performance and liver health in weaning piglets. METHODS: This study consisted of 2 experiments. In the both experiments, piglets were weaned at 21 days of age. In Exp. 1, at 21 (W0), 22 (W1), 25 (W4), 28 (W7), and 35 (W14) days of age, 6 piglets were slaughtered at each timepoint. In Exp. 2, piglets were divided into 2 groups: one received MA gavage (MA) and the other received saline gavage (CON). At 25 days of age, 6 piglets from each group were sacrificed. RESULTS: In Exp. 1, weaning caused growth inhibition and liver developmental retardation from W0 to W4. The mRNA sequencing between W0 and W4 revealed that pathways related to "regulation of apoptotic process" and "reactive oxygen species metabolic process" were enriched. Further study showed that weaning led to higher hepatic content of reactive oxygen species (ROS), H2O2 and O2-. Weaning enhanced mitochondrial fission and suppressed their fusion, activated mitophagy, thus triggering cell apoptosis. In Exp. 2, MA improved growth performance of piglets with higher average daily gain (ADG) and average daily feed intake (ADFI). The hepatic ROS, as well as products of oxidative damage malonaldehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the MA group decreased significantly than that of the CON group. The MA elevated mitochondrial membrane potential, increased activity of mitochondrial respiratory chain complexes (MRC) I and IV, enhanced mitochondrial fusion and reduced mitophagy, thus decreasing cell apoptosis. CONCLUSIONS: The present study showed that MA improved the growth performance of weaning piglets and reversed weaning-induced oxidative damage, mitochondrial dysfunction, and apoptosis. Our results suggested that MA had promising prospects for maintaining liver health in weaning piglets and provided a reference for studies of liver diseases in humans.

Bismuth Nanoparticles and Single Iron Atoms on Carbon Derived from a Covalent Organic Framework Synergistically Catalyze the Oxygen Reduction Reaction.

The utilization of catalysts comprising metal nanoparticle has been beneficial for enhancing the performance of oxygen reduction reaction (ORR). However, the unsatisfactory intrinsic activity of these catalysts still presents a significant challenge, limiting their overall effectiveness. This issue can be addressed by introducing single atoms, which can create a synergistic effect with the nanoparticles to catalyse and thereby improve performance. Nevertheless, the synergistic catalysis of nanoparticles and single atoms is still being explored. In this study, we fabricated a core-shell structured carbon framework with Fe single atoms and Bi nanoparticles through the pyrolysis of COF and MOF core-shell structures. Introducing Fe single atoms into ZIF-8, with Fe-ZIF-8 as the core and Bi-containing COF as the shell, resulted in higher ORR activity. The catalyst exhibited a half-wave potential of 0.867 V and a high current density of 6.68 mA cm-2 in 0.1 M KOH, which were comparable to those of Pt/C equivalent.  This study provides new research concepts for exploring the application of single atoms and nanoparticles in catalytic oxygen reduction reactions through synergistic effects.

Microbe-Derived Antioxidants Protect IPEC-1 Cells from H2O2-Induced Oxidative Stress, Inflammation and Tight Junction Protein Disruption via Activating the Nrf2 Pathway to Inhibit the ROS/NLRP3/IL-1ß Signaling Pathway.

Oxidative stress can induce inflammation and tight junction disruption in enterocytes. The initiation of inflammation is thought to commence with the activation of the ROS/NLRP3/IL-1ß signaling pathway, marking a crucial starting point in the process. In our previous studies, we found that microbe-derived antioxidants (MAs) showed significant potential in enhancing both antioxidant capabilities and anti-inflammatory effects. The main aim of this research was to investigate the ability of MAs to protect cells from oxidative stress caused by H2O2, to reduce inflammatory responses, and to maintain the integrity of tight junction proteins by modulating the ROS/NLRP3/IL-1ß signaling pathway. IPEC-1 cells (1 × 104 cells/well) were initially exposed to 100 mg/L of MAs for 12 h, after which they were subjected to 1 mM H2O2 treatment for 1 h. We utilized small interfering RNA (siRNA) to inhibit the expression of NLRP3 and Nrf2. Inflammatory factors such as IL-1ß and antioxidant enzyme activity levels were detected by ELISA. Oxidative stress marker ROS was examined by fluorescence analysis. The NLRP3/IL-1ß signaling pathway, Nrf2/HO-1 signaling pathway and tight junction proteins (ZO-1 and Occludin) were detected by RT-qPCR or Western blotting. In our research, it was observed that MA treatment effectively suppressed the notable increase in H2O2-induced inflammatory markers (TNF-α, IL-1ß, and IL-18), decreased ROS accumulation, mitigated the expression of NLRP3, ASC, and caspase-1, and promoted the expression of ZO-1 and Occludin. After silencing the NLRP3 gene with siRNA, the protective influence of MAs was observed to be linked with the NLRP3 inflammasome. Additional investigations demonstrated that the treatment with MAs triggered the activation of Nrf2, facilitating its translocation into the nucleus. This process resulted in a notable upregulation of Nrf2, NQO1, and HO-1 expression, along with the initiation of the Nrf2-HO-1 signaling pathway. Consequently, there was an enhancement in the activities of antioxidant enzymes like SOD, GSH-Px, and CAT, which effectively mitigated the accumulation of ROS, thereby ameliorating the oxidative stress state. The antioxidant effectiveness of MAs was additionally heightened in the presence of SFN, an activator of Nrf2. The antioxidant and anti-inflammatory functions of MAs and their role in regulating intestinal epithelial tight junction protein disruption were significantly affected after siRNA knockdown of the Nrf2 gene. These findings suggest that MAs have the potential to reduce H2O2-triggered oxidative stress, inflammation, and disruption of intestinal epithelial tight junction proteins in IPEC-1 cells. This reduction is achieved by blocking the ROS/NLRP3/IL-1ß signaling pathway through the activation of the Nrf2 pathway.

Microbe-derived Antioxidants Enhance Lipid Synthesis by Regulating the Hepatic AMPKα-SREBP1c Pathway in Weanling Piglets.

BACKGROUND: Weaning usually causes low feed intake and weight loss in piglets, which mobilizes lipid to energize. The microbe-derived antioxidants (MAs) exhibit great potential in antioxidation, anti-inflammation, and metabolic regulation. OBJECTIVES: We aimed to investigate the changes of lipid metabolism postweaning and effects of MA on growth performance and hepatic lipid metabolism in weanling piglets. METHODS: In the first experiment, piglets weaned at 21 d of age were slaughtered on weaning day (d0), 4 (d4), and 14 (d14) postweaning (6 piglets per day). In the second experiment, piglets were divided into 2 groups, receiving MA (MA) and saline gavage (CON), respectively. All piglets were weaned at 21 d of age and 6 piglets from each group were slaughtered at 25 d of age. RESULTS: In experiment 1, the serum triglyceride, total cholesterol (TC), and LDL cholesterol on d4 and d14 declined significantly compared with d0 (P < 0.05). The serum leptin on d0 was higher than that on d4 and d14 (P < 0.05). The serum ghrelin kept increasing from d0 to d14 (P < 0.05). The hepatic hormone-sensitive lipase and adipose triglyceride lipase first increased from d0 to d4 and then decreased from d4 to d14 (P < 0.05). In experiment 2, the average daily gain and average daily feed intake from 21 to 25 d of age increased in the MA group compared with the CON group (P < 0.05). The serum TC, hepatic TC, and glucose of MA group showed a significant increase than that of the CON group (P < 0.05). The expression of SCD1, ACAT2, and PPARγ were upregulated in the MA group (P < 0.05). Contrary to the decreased expression of phosphorylation of adenosine 5'-monophosphate-activated protein kinase alfa subunit (Thr172), the nuclear sterol regulatory element-binding protein 1c, fatty acid synthase, and peroxisome proliferator-activated receptor gamma of MA group increased than that of CON group (P < 0.05). CONCLUSIONS: Weaning promoted hepatic lipolysis and MA could enhance lipid synthesis by regulating adenosine 5'-monophosphate-activated protein kinase alfa subunit-sterol regulatory element-binding protein 1c pathway, thus improving growth performance of weanling piglets.

Remodeling of Hepatic Glucose Metabolism in Response to Early Weaning in Piglets.

This study aimed to investigate the dynamic changes in hepatic glucose metabolism in response to early weaning. A total of 60 piglets were randomly selected and weaned at 21 days old. Six piglets were slaughtered on the weaning day (d0) and at 1 (d1), 4 (d4), 7 (d7), and 14 (d14) days postweaning. The results illustrated that body weight significantly increased from d4 to d14 (p < 0.001). Serum glucose fell sharply after weaning and then remained at a low level from d1 to d14 (p < 0.001). Serum insulin decreased from d4 (p < 0.001), which caused hepatic glycogen to be broken down (p = 0.007). The glucose-6-phosphatase activity increased from d0 to d4 and then decreased from d4 to d14 (p = 0.039). The pyruvate carboxylase activity presented a significant sustained increase from d0 to d14 (p < 0.001). The succinate (p = 0.006) and oxaloacetate (p = 0.003) content on d4 was lower than that on d0. The succinate dehydrogenase activity (p = 0.008) and ATP (p = 0.016) production decreased significantly on d4 compared to that on d0. Taken together, these findings reveal the dynamic changes of metabolites and enzymes related to hepatic glycometabolism and the TCA (tricarboxylic acid) cycle in piglets after weaning. Our findings enrich weaning stress theory and might provide a reference for dietary intervention.

Construction of nano-silica particle clusters and their effects on the shear thickening properties of liquids.

It is of great research significance to prepare a new shear thickening fluid (STF) with a simple process, remarkable thickening effect and excellent impact resistance from the properties of the particles. Inspired by the shear thickening mechanism, nano-silica particle clusters (SPC) with different morphological structures were prepared by the reaction of amino-modified silica with polyethylene glycol diglycidyl ether (PEGDGE), and the structure models of particle clusters were designed through theoretical analysis. The structure of SPC was affected by the degree of amination modification and the molecular weight of PEGDGE, which was analyzed by DLS and TEM. The shear thickening behavior of the fluid was evaluated by steady-state rheology and dynamic-state rheology analysis. The shear thickening behavior of the fluid composed of SPC also changed greatly with the influence of the degree of amination modification and the molecular weight of PEGDGE. In addition, compared with the STF contained original silica, the STF contained SPC could produce a faster and stronger shear thickening response. Therefore, silica particle clusters are not only a promising candidate for the preparation of high-performance shear thickening fluids, but can also be better applied to industrial and scientific fields such as impact protection and shock absorption.

A cation-π interaction confined graphene oxide membrane for separation of light paraffins and olefins.

A supported graphene oxide membrane is endowed with selective function for olefins by a cation intercalation method. The metal-cation fixed GO membrane exhibits a high propane to propylene ideal selectivity of 1817 for single gas and a separation factor of 7.1 for binary mixtures with fast gas permeance in the order of 10-7 mol m-2 s-1 Pa-1 and reliable permeation stability.

Formulation and stabilization of high internal phase emulsions: Stabilization by cellulose nanocrystals and gelatinized soluble starch.

In this work, high internal phase emulsions (HIPEs) stabilized by naturally derived cellulose nanocrystals (CNC) and gelatinized soluble starch (GSS) were fabricated to stabilize oregano essential oil (OEO) in the absence of surfactant. The physical properties, microstructures, rheological properties, and storage stability of HIPEs were investigated by adjusting CNC contents (0.2, 0.3, 0.4 and 0.5 wt%) and starch concentration (4.5 wt%). The results revealed that CNC-GSS stabilized HIPEs exhibited good storage stability within one month and the smallest droplets size at a CNC concentration of 0.4 wt%. The emulsion volume fractions of 0.2, 0.3, 0.4 and 0.5 wt% CNC-GSS stabilized HIPEs after centrifugation reached 77.58, 82.05, 94.22, and 91.41 %, respectively. The effect of native CNC and GSS were analyzed to understand the stability mechanisms of HIPEs. The results revealed that CNC could be used as an effective stabilizer and emulsifier to fabricate the stable and gel-like HIPEs with tunable microstructure and rheological properties.

Microbe-Derived Antioxidants Alleviate Liver and Adipose Tissue Lipid Disorders and Metabolic Inflammation Induced by High Fat Diet in Mice.

Obesity induces lipodystrophy and metabolic inflammation. Microbe-derived antioxidants (MA) are novel small-molecule nutrients obtained from microbial fermentation, and have anti-oxidation, lipid-lowering and anti-inflammatory effects. Whether MA can regulate obesity-induced lipodystrophy and metabolic inflammation has not yet been investigated. The aim of this study was to investigate the effects of MA on oxidative stress, lipid disorders, and metabolic inflammation in liver and epididymal adipose tissues (EAT) of mice fed with a high-fat diet (HFD). Results showed that MA was able to reverse the HFD-induced increase in body weight, body fat rate and Lee's index in mice; reduce the fat content in serum, liver and EAT; and regulate the INS, LEP and resistin adipokines as well as free fatty acids to their normal levels. MA also reduced de novo synthesis of fat in the liver and EAT and promoted gene expression for lipolysis, fatty acid transport and ß-oxidation. MA decreased TNF-α and MCP1 content in serum, elevated SOD activity in liver and EAT, induced macrophage polarization toward the M2 type, inhibited the NLRP3 pathway, increased gene expression of the anti-inflammatory factors IL-4 and IL-13 and suppressed gene expression of the pro-inflammatory factors IL-6, TNF-α and MCP1, thereby attenuating oxidative stress and inflammation induced by HFD. In conclusion, MA can effectively reduce HFD-induced weight gain and alleviate obesity-induced oxidative stress, lipid disorders and metabolic inflammation in the liver and EAT, indicating that MA shows great promise as a functional food.

Berberine Regulation of Cellular Oxidative Stress, Apoptosis and Autophagy by Modulation of m6A mRNA Methylation through Targeting the Camk1db/ERK Pathway in Zebrafish-Hepatocytes.

Berberine (BBR) ameliorates cellular oxidative stress, apoptosis and autophagy induced by lipid metabolism disorder, however, the molecular mechanism associated with it is not well known. To study the mechanism, we started with m6A methylation modification to investigate its role in lipid deposition zebrafish hepatocytes (ZFL). The results showed that BBR could change the cellular m6A RNA methylation level, increase m6A levels of Camk1db gene transcript and alter Camk1db gene mRNA expression. Via knockdown of the Camk1db gene, Camk1db could promote cellular ERK phosphorylation levels. Berberine regulated the expression level of Camk1db mRNA by altering the M6A RNA methylation of the Camk1db gene, which further affected the synthesis of calmodulin-dependent protein kinase and activated ERK signaling pathway resulting in changes in downstream physiological indicators including ROS production, cell proliferation, apoptosis and autophagy. In conclusion, berberine could regulate cellular oxidative stress, apoptosis and autophagy by mediating Camk1db m6A methylation through the targeting of the Camk1db/ERK pathway in zebrafish-hepatocyte.