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This study aimed to investigate effects of dietary lycopene supplementation on meat quality, antioxidant ability and muscle fiber type transformation in finishing pigs. In a 70-day experiment, eighteen Duroc × Landrace × Yorkshire barrows were randomly allocated to 3 dietary treatments including a basal diet supplemented with 0, 100 and 200 mg/kg lycopene, respectively. Each dietary treatment had 6 replicates with one pig each. Results showed that dietary 200 mg/kg lycopene supplementation increased muscle redness a* value, intramuscular fat and crude protein contents, and decreased muscle lightness L* and yellowness b* values (P ˂ 0.05), suggesting that addition of 200 mg/kg lycopene to the diet of finishing pigs improved color, nutritional value and juiciness of pork after slaughter. Results also showed that dietary lycopene supplementation enhanced antioxidant capacity of finishing pigs (P ˂ 0.05). Moreover, dietary supplementation of 200 mg/kg lycopene significantly increased slow myosin heavy chain (MyHC) protein level and slow-twitch fiber percentage, and decreased fast MyHC protein level and fast-twitch fiber percentage (P ˂ 0.05), suggesting that the addition of 200 mg/kg lycopene to the diet of finishing pigs promoted muscle fiber type conversion from fast-twitch to slow-twitch. Together, we provide the first evidence that dietary 200 mg/kg lycopene supplementation improves meat quality, enhances antioxidant capacity and promotes muscle fiber type transformation from fast-twitch to slow-twitch in finishing pigs.

This experiment was conducted to evaluate the effects of different levels of tannic acid (TA) on growth performance, diarrhea rate, nutrient digestibility and intestinal health in weaned piglets. A total of 180 weaned piglets (Duroc × Landrace × Yorkshire, 24 d of age, initial average BW = 7.77 ± 0.17 kg) were allotted to 5 groups (6 pigs/pen and 6 replicates/group) in a randomized complete block design according to their gender and body weight. Piglets were fed a basal diet, or the basal diet supplemented with 0.05%, 0.1%, 0.2% or 0.4% TA for 28 d. The supplementary levels of TA in the diets were obtained by adding tannalbin containing 51% TA and 40.17% protein. The results showed that, compared with the CON group, dietary TA did not affect ADFI, ADG or F:G, and linearly reduced (P

Diarrhoea caused by pathogens such as enterotoxigenic E. coli (ETEC) is a serious threat to the health of young animals and human infants. Here, we investigated the protective effect of fructo-oligosaccharides (FOS) on the intestinal epithelium with ETEC challenge in a weaned piglet model. Twenty-four weaned piglets were randomly divided into three groups: (1) non-ETEC-challenged control (CON); (2) ETEC-challenged control (ECON); and (3) ETEC challenge + 2·5 g/kg FOS (EFOS). On day 19, the CON pigs were orally infused with sterile culture, while the ECON and EFOS pigs were orally infused with active ETEC (2·5 × 109 colony-forming units). On day 21, pigs were slaughtered to collect venous blood and small intestine. Result showed that the pre-treatment of FOS improved the antioxidant capacity and the integrity of intestinal barrier in the ETEC-challenged pigs without affecting their growth performance. Specifically, compared with ECON pigs, the level of GSH peroxidase and catalase in the plasma and intestinal mucosa of EFOS pigs was increased (P < 0·05), and the intestinal barrier marked by zonula occluden-1 and plasmatic diamine oxidase was also improved in EFOS pigs. A lower level (P < 0·05) of inflammatory cytokines in the intestinal mucosa of EFOS pigs might be involved in the inhibition of TLR4/MYD88/NF-κB pathway. The apoptosis of jejunal cells in EFOS pigs was also lower than that in ECON pigs (P < 0·05). Our findings provide convincing evidence of possible prebiotic and protective effect of FOS on the maintenance of intestinal epithelial function under the attack of pathogens.

Microglial activation and neuroinflammation induced by amyloid β (Aβ) play pivotal roles in Alzheimer's disease (AD) pathogenesis. Astragaloside IV (AS-IV) is one of the major active compounds of the traditional Chinese medicine Astmgali Radix. It has been reported that AS-IV could protect against Aβ-induced neuroinflammation and cognitive impairment, but the underlying mechanisms need to be further clarified. In this study, the therapeutic effects of AS-IV were investigated in an oligomeric Aβ (oAβ) induced AD mice model. The effects of AS-IV on microglial activation, neuronal damage and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression were further studied. Different doses of AS-IV were administered intragastrically once a day after intracerebroventricularly oAβ injection. Results of behavioral experiments including novel object recognition (NOR) test and Morris water maze (MWM) test revealed that AS-IV administration could significantly ameliorate oAβ-induced cognitive impairment in a dose dependent manner. Enzyme linked immunosorbent assay (ELISA) results showed that increased levels of reactive oxygen species (ROS), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and IL-6 in hippocampal tissues induced by oAβ injection were remarkably inhibited after AS-IV treatment. OAβ induced microglial activation and neuronal damage was significantly suppressed in AS-IV-treated mice brain, observed in immunohistochemistry results. Furthermore, oAβ upregulated protein expression of NADPH oxidase subunits gp91phox, p47phox, p22phox and p67phox were remarkably reduced by AS-IV in Western blotting assay. These results revealed that AS-IV could ameliorate oAβ-induced cognitive impairment, neuroinflammation and neuronal damage, which were possibly mediated by inhibition of microglial activation and down-regulation of NADPH oxidase protein expression. Our findings provide new insights of AS-IV for the treatment of neuroinflammation related diseases such as AD.

microRNAs act as fine-tuners in the regulation of plant growth and resistance against biotic and abiotic stress. Here we demonstrate that rice miR1432 fine-tunes yield and blast disease resistance via different modules. Overexpression of miR1432 leads to compromised resistance and decreased yield, whereas blocking miR1432 using a target mimic of miR1432 results in enhanced resistance and yield. miR1432 suppresses the expression ofLOC_Os03g59790, which encodes an EF-hand family protein 1 (OsEFH1). Overexpression ofOsEFH1leads to enhanced rice resistance but decreased grain yield. Further study revealed that miR1432 andOsEFH1are differentially responsive to chitin, a fungus-derived pathogen/microbe-associated molecular pattern (PAMP/MAMP). Consistently, blocking miR1432 or overexpression ofOsEFH1improves chitin-triggered immunity responses. In contrast, overexpression ofACOT, another target gene regulating rice yield traits, has no significant effects on rice blast disease resistance. Altogether, these results indicate that miR1432 balances yield and resistance via different target genes, and blocking miR1432 can simultaneously improve yield and resistance.

The medicinal plant Artemisia annua L. is presently the sole plant source of artemisinin, the key ingredient of first-line antimalarial drug. As the content of artemisinin in the native plant is very low, the growth and artemisinin biosynthesis of A. annua attract extensive attentions. Endophytic microbes, which spend their entire life spans within plant tissue are widespread in healthy A. annua plants. Although endophytes have emerged in recent years as the novel resources for secondary metabolites of antioxidant, antimicrobial and anticancer activities, the roles of endophytes in plant growth and metabolism have not been fully understood. This review presents the current development of researches into endophytes in model medicinal herb A. annua and focuses on the regulatory roles of endophytes. We introduced the isolation, cultivation and identification method for endophytes in A. annua. Distribution, biodiversity and novel bioactive metabolites of the endophytes were presented. Endophytes promoted the growth of A. annua through the enhanced photosynthesis, nutrient acquisition and phytohormones. The defense resistance against microbial pathogens of A. annua was partially involved with endophyte metabolites. The development of glandular secretory trichomes and the oxidative stress induced by endophytes could be key factors for enhanced artemisinin production. Understanding the endophyte-host partnerships has the potential to improve agricultural practices for A. annua growth and artemisinin production. The aim of this review is to shed light on the importance of endophytes in plant growth and the production of medicinally important secondary metabolites.

Dysregulation of NLRP3 inflammasome results in uncontrolled inflammation, which participates in various chronic diseases. TWIK2 potassium channel mediates potassium efflux that has been reported to be an essential upstream mechanism for ATP-induced NLRP3 inflammasome activation. Thus, TWIK2 potassium channel could be a potential drug target for NLRP3-related inflammatory diseases. In the present study we investigated the effects of known K2P channel modulators on TWIK2 channel expressed in a heterologous system. In order to increase plasma membrane expression and thus TWIK2 currents, a mutant channel with three mutations (TWIK2(I289A/L290A/Y308A)) in the C-terminus was expressed in COS-7 cells. TWIK2 currents were assessed using whole-cell voltage-clamp recording. Among 6 known K2P channel modulators tested (DCPIB, quinine, fluoxetine, ML365, ML335, and TKDC), ML365 was the most potent TWIK2 channel blocker with an IC(50) value of 4.07 ± 1.5 μM. Furthermore, ML365 selectively inhibited TWIK2 without affecting TWIK1 or THIK1 channels. We showed that ML365 (1, 5 μM) concentration-dependently inhibited ATP-induced NLRP3 inflammasome activation in LPS-primed murine BMDMs, whereas it did not affect nigericin-induced NLRP3, or non-canonical, AIM2 and NLRC4 inflammasomes activation. Knockdown of TWIK2 significantly impaired the inhibitory effect of ML365 on ATP-induced NLRP3 inflammasome activation. Moreover, we demonstrated that pre-administration of ML365 (1, 10, 25 mg/kg, ip) dose-dependently ameliorated LPS-induced endotoxic shock in mice. In a preliminary pharmacokinetic study conducted in rats, ML365 showed good absolute oral bioavailability with F value of 22.49%. In conclusion, ML365 provides a structural reference for future design of selective TWIK2 channel inhibitors in treating related inflammatory diseases.

Summary Methanol is a promising feedstock for biomanufacturing of fuels and chemicals. Although efforts have been made to engineer platform microorganisms for methanol bioconversion, the substrate uptake and cell growth rates on methanol are still unsatisfactory, suggesting certain limiting factors remain unsolved. Herein, we analysed the global metabolic regulation changes between an evolved methanol‐dependent Corynebacterium glutamicum mutant and its ancestral strain by transcriptome analysis. Many genes involved in central metabolism including glycolysis, amino acid biosynthesis and energy generation were regulated, implying the adaptive laboratory evolution reprogrammed the cellular metabolism for methanol utilization. We then demonstrated that nitrate could serve as a complementary electron acceptor for aerobic methanol metabolism, and the biosynthesis of several amino acids limited methylotrophic growth. Finally, the sedoheptulose bisphosphatase pathway for generating methanol assimilation acceptor was found effective in C. glutamicum. This study identifies limiting factors of methanol metabolism and provides engineering targets for developing superior synthetic methylotrophs., Transcriptome analysis of methanol‐dependent Corynebacterium glutamicum reveals metabolic regulation changes in central metabolism. It is experimentally verified that nitrate could serve as an additional electron acceptor for aerobic methanol metabolism and the biosynthesis of several amino acids limits methylotrophic growth, and the SBPase variant for Ru5P regeneration is effective in methylotrophic C. glutamicum.

There are appreciable does of raffinose in soybean, but the impacts of raffinose on pigs are poorly investigated. We used 2 experiments to investigate the influence of soybean raffinose on growth performance, digestibility, humoral immunity and intestinal morphology of growing pigs. In Exp. 1, a total of 30 crossbred (Duroc × Landrace × Yorkshire) barrows (21.93 ± 0.43 kg) were randomly divided into 3 groups, and were fed with the control diet, the control diets supplemented with 0.2% and 0.5% raffinose, respectively, for 21 d. Results showed that the addition of 0.2% or 0.5% raffinose reduced (P

In this study, we investigated the solid–liquid phase equilibria of the quaternary system Na+, Mg2+//CO32–, SO42––H2O and its four ternary subsystems at 298.15 K and atmospheric pressure using the ...

The toxic C1 compounds methanol and formaldehyde are generated during bioconversion of lignin into value-added chemicals. These toxins can be detoxified and assimilated by methylotrophs to synthesize useful metabolites and cell biomass. We discuss the promising future of constructing integrated biosystems to use toxic C1 byproducts and promote lignin valorization.

Background Ferulic acid (FA) is a common polyphenolic compound. The purpose of this study was to explore the effect of dietary FA supplementation on growth performance and muscle fiber type conversion in weaned piglets. In this study, eighteen 21-day-old DLY (Duroc × Landrace × Yorkshire) weaned piglets were randomly divided into control, 0.05% FA, and 0.45% FA groups. Results Our study showed that dietary FA supplementation had no effect on growth performance, but it could upregulate the expression of slow myosin heavy chain (MyHC) protein, increase the activities of succinic dehydrogenase and malate dehydrogenase, and downregulate the expression of fast MyHC protein. Dietary FA supplementation also increased the expression levels of phosphorylated AMP-activated protein kinase, sirtuin 1 (Sirt1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), myocyte enhancer factor 2C, and troponin I-SS, increased the proportion of slow-twitch fiber, and decreased the proportion of fast-twitch fiber. In addition, our results showed that dietary FA supplementation increased the messenger RNA abundance of mitochondrial nuclear transcription genes, including ATP synthase membrane subunit c locus 1, cytochrome oxidase subunit 1, nuclear respiratory factor 1, mitochondrial transcription factor A, mitochondrial transcription factor B1, and cytochrome c. Conclusion We provided the first evidence that FA could promote muscle fiber type conversion from fast-twitch to slow-twitch via the Sirt1/AMP-activated protein kinase/PGC-1α signaling pathway and could improve the mitochondrial function in weaned piglets. This means that FA can be used as a dietary supplement to improve the quality of pork. © 2021 Society of Chemical Industry.

To investigate the influence of baseline enterotypes and dietary starch type on the concentration of short-chain fatty acids (SCFA), numbers of butyrate producing bacteria and the expression of genes related to intestinal barrier and inflammatory response in the colon of finishing pigs, a 60-d in vivo trial was conducted. A 2-wk pre-trial with 102 crossbred (Duroc × [Landrace × Yorkshire]) finishing barrows (90 d old) was conducted to screen enterotypes. Then, a total of 32 pigs (87.40 ± 2.76 kg) with high (HPBR, ≥ 14) and low (LPBR, ≤ 2) Prevotella-to-Bacteroides ratios (PBR) in equal measure were selected and randomly divided into 4 groups with 8 replicates per group and 1 pig per replicate. The trial was designed following a 2 (PBR) × 2 (amylose-to-amylopectin ratio, AMR) factorial arrangement. Pigs with different PBR were fed diets based on corn-soybean meal with high AMR (HAMR, 1.24) or low AMR (LAMR, 0.23), respectively. Results showed that neither PBR nor AMR influenced the growth performance of pigs. HPBR pigs fed HAMR diet had a higher number of colonic Clostridium cluster XIVa and higher gene expression of butyrate kinase compared to the LPBR pigs (P

Ni-based catalysts are the most promising catalysts for CO2 methanation. The development of catalysts with low-temperature activity could bring significant energy and environmental benefits. In this work, the hydrogenation of CO2 to methane was studied on Ni-M/γ-Al2O3 (M = Fe, Co, or Mn) bimetallic catalysts. The optimum reaction was obtained using Ni-Mn/γ-Al2O3 (CO2 conversion: 85%, CH4 selectivity: 99%, 280 °C). In situ FTIR studies revealed the excellent performance of Ni-Mn/γ-Al2O3, which lowers the required reaction temperature. Based on in situ FTIR studies, CO2 methanation proceeded over three intermediates on the catalysts: bicarbonate → carbonate → formate → methane. The second metal (Co or Mn) promoted the dispersion of both Ni and itself and improved the ability of Ni to crack H2. And introduced more oxygen vacancies to strengthen the basicity of surrounding O2− on the surface of the catalysts. In effect, the number of carbonate active sites could be increased accordingly, thereby improving the adsorption capacity for CO2.

Endoplasmic reticulum stress (ERS) and apoptosis are widely considered as essential factors associated with intestinal disorders, whereas nutritional therapeutic approaches targeting ERS may control disease activity. Thus, we focus on the potential benefit of chitosan oligosaccharide (COS) on repressing ERS and ERS-induced apoptosis. In this study, we used the ERS model with tunicamycin (TM)-induced IPEC-J2 cells in vitro and nutrient deprivation-induced ERS in piglets to evaluate the protective mechanism of COS against ERS and ERS-induced apoptosis. The results showed that cells were characterized by activation of the unfolded protein response (UPR) and increased epithelial apoptosis upon exposure to TM. However, these changes were significantly attenuated by COS and the expressions of Akt and mTORC1 were inhibited. Furthermore, a specific inhibitor of mTOR confirmed the suppression of Akt and reduced the activation of the UPR and apoptosis. In vivo, COS protected against nutrient deprivation-induced ERS in the jejunum of piglets, in which the overexpression of the UPR and apoptosis was rescued. Consistently, COS attenuated nutrient deprivation-induced disruption of intestinal barrier integrity and functional capacity. Together, we provided the first evidence that COS could protect against intestinal apoptosis through alleviating severe ERS, which may be related to the inhibition of the Akt/mTOR signaling pathway.

Reprogramming complex cellular metabolism requires simultaneous regulation of multigene expression. Ex-situ cloning-based methods are commonly used, but the target gene number and combinatorial library size are severely limited by cloning and transformation efficiencies. In-situ methods such as multiplex automated genome engineering (MAGE) depends on high-efficiency transformation and incorporation of heterologous DNA donors, which are limited to few microorganisms. Here, we describe a Base Editor-Targeted and Template-free Expression Regulation (BETTER) method for simultaneously diversifying multigene expression. BETTER repurposes CRISPR-guided base editors and in-situ generates large numbers of genetic combinations of diverse ribosome binding sites, 5’ untranslated regions, or promoters, without library construction, transformation, and incorporation of DNA donors. We apply BETTER to simultaneously regulate expression of up to ten genes in industrial and model microorganisms Corynebacterium glutamicum and Bacillus subtilis. Variants with improved xylose catabolism, glycerol catabolism, or lycopene biosynthesis are respectively obtained. This technology will be useful for large-scale fine-tuning of multigene expression in both genetically tractable and intractable microorganisms., To obtain optimal yield and productivity in bioproduction, expression of pathway genes must be appropriately coordinated. Here, the authors report repurposing of base editors for simultaneous regulation of multiple gene expression and demonstrate its application in industrially important and model microorganisms.

Triazole and phenanthroimidazole moieties are commonly used to construct efficient blue-emitting materials as acceptors and donors, respectively. Benefitting from the D–A coupling of the two moieties, two novel bipolar blue emitters, TAZ-PPI and 4NTAZ-PPI, were synthesized. They showed excellent thermal stability and high photoluminescence quantum yields (PLQYs). Non-doped blue organic light-emitting diodes (OLEDs) based on 4NTAZ-PPI and TAZ-PPI present maximum external quantum efficiencies of 7.3% and 5.9%, respectively, and exhibit negligible efficiency roll-off. The CIE coordinates are (0.149, 0.131) and (0.149, 0.130) at a luminance of 1000 cd m−2, respectively. Because the combination of electron donors and acceptors is a favorable method to balance the carrier injection and transport, 4NTAZ-PPI and TAZ-PPI exhibit excellent hole and electron transporting capabilities.

Covalent organic polymers (COPs) are designable porous organic polymers that have attracted increasing research interest and have developed as electrode materials for supercapacitors. By using an easy synthesis method, a novel phosphazene-anthraquinone-based covalent organic polymer (HD-1) was successfully designed and synthesized through a polymerization reaction between hexachlorocyclotriphosphazene (HCCP) and 2,6-diaminoanthraquinone (DAAQ) in dimethylsulphoxide (DMSO). Fourier transform infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS), nitrogen adsorption–desorption analysis, powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), energy dispersive X-ray spectrometr (EDX) and thermogravimetric analysis (TGA) were used to characterize the structure and properties of HD-1. The specific surface was calculated as 249.2 m2 g−1. The specific capacitance of HD-1 was 125.6 F g−1 at a current density of 0.5 A g−1 in a 6.0 M potassium hydroxide electrolyte. After 20 000 GCD cycles, the specific capacitance retention was about 92.8% of its initial capacitance.

To explore the effect of manno-oligosaccharide (MOS) on intestinal health in weaned pigs upon enterotoxigenic Escherichia coli K88 (ETEC) challenge, thirty-two male weaned pigs were randomly assigned into four groups. Pigs fed with a basal diet or basal diet containing MOS (0·6 g/kg) were orally infused with ETEC or culture medium. Results showed that MOS significantly elevated the digestibility of crude protein and gross energy in both ETEC-challenged and non-challenged pigs (P < 0·05). MOS also elevated serum concentrations of IgA and IgM (P < 0·05), but decreased serum concentrations of TNF-α, IL-1β and IL-6 (P < 0·05) in ETEC-challenged pigs. Interestingly, MOS increased villus height and the ratio of villus height:crypt depth in duodenum and ileum (P < 0·05). MOS also increased duodenal sucrase and ileal lactase activity in ETEC-challenged pigs (P < 0·05). MOS decreased the abundance of E. coli, but increased the abundance of Lactobacillus, Bifidobacterium and Bacillus in caecum (P < 0·05). Importantly, MOS not only elevated the expression levels of zonula occludens-1 (ZO-1), claudin-1 and GLUT-2 in duodenum (P < 0·05) but also elevated the expression levels of ZO-1, GLUT-2 and L-type amino acid transporter-1 in ileum (P < 0·05) upon ETEC challenge. These results suggested that MOS can alleviate inflammation and intestinal injury in weaned pigs upon ETEC challenge, which was associated with suppressed secretion of inflammatory cytokines and elevated serum Ig, as well as improved intestinal epithelium functions and microbiota.

Organic polymers have been found widespread commercial applications due to their easy processing and attractive mechanical properties. Concurrently, inorganic polyoxometalates (POMs), a class of metal-oxygen anionic and nanosized clusters of early transition metals, have a wide range of attractive functions and are used in industrial catalysis. In this communication, we report a new approach to creating the first linear poly(polyoxometalate)s that combine the advantages of polymers and POM clusters. In the experiment, a POM-containing norbornene monomer was first synthesized by linking a Wells-Dawson-type POM with a norbornene derivative. The monomer was polymerized in the presence of a Grubbs catalyst under mild conditions with yields nearly 100% in a living and controllable manner. The resulting poly(polyoxometalate)s have controllable molecular weights and a well-defined hybrid structure of an organic polynorbornene backbone with large pendant groups of the nanosized POM clusters. Thus, they form good films and have a good catalytic performance. Our findings not only pave the way for incorporating the POM clusters into polymers with well-defined structures and high molecular weights, but also offer a competitive strategy for developing more novel catalytic systems by introducing the poly(polyoxometalate)s.

Anaerobic methane oxidation is coupled to the reduction of electron acceptors, such as sulfate, and contributes to their biogeochemical cycling in the environment. However, whether arsenate acts as an alternative electron acceptor of anaerobic methane oxidation and how this influences global arsenic transformations remains elusive. Here, we present incubations of arsenate-contaminated wetland soils from seven provinces in China. Using isotopically labelled methane, we find that anaerobic methane oxidation was linked to arsenate reduction at a rate approaching the theoretical arsenic/methane stoichiometric ratio of 4. In microcosm incubations with natural wetland soils, we find that the coupled pathway of anaerobic methane oxidation and arsenate reduction contributed 26 to 49% of total arsenic release from soils, with arsenic in the more soluble and toxic form arsenite. Comparative gene quantification and metagenomic sequencing suggest that the coupled pathway was facilitated by anaerobic methanotrophs, either independently or synergistically with arsenate-reducing bacteria through reverse methanogenesis and respiratory arsenate reduction. Further bioinformatic analyses show that genes coding for reverse methanogenesis and respiratory arsenate reduction are universally co-distributed in nature. This suggests that coupling of anaerobic methane oxidation and arsenate reduction is a potentially global but previously overlooked process, with implications for arsenic mobilization and environmental contamination. The coupling of anaerobic oxidation of methane and arsenate reduction is an important pathway of releasing arsenic from soils, according to incubation experiments of arsenate-contaminated wetland soils.

Background Tannic acid (TA) is potential to reduce diarrhea in weaning pigs, but knowledge about the influence of TA on intestinal barrier integrity and function is still scarce. This experiment was conducted to investigate the effects of dietary TA supplementation on growth performance, diarrhea rate, intestinal barrier integrity and function of weaned pigs. Methods A total of 108 crossbred (Duroc × Landrace × Yorkshire) piglets, with an initial average body weight of 6.60 ± 0.27 kg, were allotted to 3 groups (6 pigs/pen and 6 replicates/group) in a randomized complete block design according to their gender and body weight. Piglets were fed the basal diet with 0 (control, CON), 0.2% and 1.0% TA, respectively. The trial lasted for 28 d. Results Compared with the CON group, dietary 0.2% and 1.0% TA supplementation didn’t affect ADFI, ADG and F:G (P > 0.05), but reduced diarrhea rate, diarrhea index and diarrhea score of piglets (P P P P P P P OCLN) mRNA and 0.2% TA group had higher zonula occludens-2 (ZO-2) level (P OCLN mRNA levels in the jejunum (P ZO-1) mRNA levels in the ileum (P Conclusion In conclusion, dietary supplementation of 0.2% or 1.0% TA could effectively alleviate post-weaning diarrhea without altering growth performance in weaned piglets, which might be achieved by improving intestinal barrier integrity and function.

Advanced oxidative protein products (AOPPs) are novel uremic toxins whose concentrations continuously increases in patients with chronic kidney disease (CKD). Epithelial-to-mesenchymal transition (EMT) of tubular cells is the main mechanism underlying CKD pathogenesis. Studies have shown that AOPPs can induce EMT and promote renal fibrosis. However, the mechanism through which AOPPs induce tubular cell-EMT is poorly understood. In this study, we aimed to clarify the mechanisms underlying AOPP-induced EMT in human kidney proximal tubular (HKC-8) epithelial cells. Small molecule inhibitor, CRISPR-Cas9 knockout technology, siRNA knockdown technology, western blot, and reverse transcription-quantitative polymerase chain reaction were applied to investigate the mechanisms underlying AOPP-induced EMT in HKC-8 cells. AOPP treatment was found to significantly induce EMT, as evidenced by increased α-smooth muscle actin (α-SMA) and decreased E-cadherin levels, and upregulated Wnt1, β-catenin, Tcf4, and Gsk-3β expression. Conversely, blockade of Wnt/β-catenin signaling using small molecule inhibitor ICG-001 hindered AOPP-induced EMT. Moreover, knockout of receptor of advanced glycation end-products (RAGE) reversed these aforementioned effects, whereas AGE receptor 1 (AGER1)-specific siRNA transfection enhanced them. Taken together, these data suggested that AOPPs could induce HKC-8 cell EMT by activating the RAGE/Wnt/β-catenin signaling pathway and AGER1 could restore EMT by antagonizing the role of RAGE. These results may provide a new theoretical basis for EMT and help identify new therapeutic targets for suppressing CKD progression.

Soy protein is wildly used in food industry due to its high nutritional value and good functionalities. However, the poor storage stability of commercial soy protein products has puzzled both the producers and the users for a long time. The current study assessed the changes in protein solubility, aggregation, oxidation, and conformation of soy protein isolate (SPI) with various soluble aggregates formed at different pH values (pH 5–8) during storage. During storage, SPI samples showed a reduced protein solubility (p, SPI powder with higher pH (before spray drying) exhibited a lower storage stability. Higher pH produced more disulfide‐mediated aggregates. More soluble aggregates in fresh SPI appeared to induce faster loss of protein solubility.

This experiment was conducted to investigate the effects of benzoic acid, Bacillus coagulans and oregano oil combined supplementation on growth performance, immune status and intestinal barrier integrity of piglets. In a 26-d experiment, 25 piglets were randomly assigned to 5 treatments: 1) a basal diet, negative control (NC), 2) NC added with antibiotics, positive control (PC); 3) NC added with benzoic acid at 3,000 g/t and Bacillus coagulans at 400 g/t (AB); 4) NC added with benzoic acid at 3,000 g/t and oregano oil at 400 g/t (AO); 5) NC added with 3,000 g/t benzoic acid and Bacillus coagulans at 400 g/t and oregano oil at 400 g/t (ABO). On d 27, all piglets were euthanized to obtain jejunal mucosa to measure immune status and intestinal barrier integrity. Results showed that pigs fed AB diet increased the final body weight and average daily body weight gain and decreased the ratio of feed to gain compared with NC group (P < 0.05). Compared with NC group, AB, AO and ABO decreased serum tumor necrosis factor-α concentration and ABO decreased interleukin-1β concentration in serum and jejunal mucosa (P < 0.05). Compared with NC group, AB up-regulated mRNA expressions of sodium-glucose cotransporte1, claudin-1, occludin and mucin2 in jejunal mucosa and the populations of Bifidobacterium and Bacillus in cecal digesta (P < 0.05). Compared with NC group, ABO increased jejunal mucosal occludin mRNA abundance and Bifidobacterium population in cecal digesta, and decreased Escherichia coli population in cecal digesta (P < 0.05). Furthermore, AB and ABO increased Bacillus population in cecal digesta compared with PC group (P < 0.05). These results indicated that dietary AB supplementation could improve growth performance and intestinal barrier integrity of piglets when fed antibiotic-free diets, which was possibly associated with the improvement of immune status and intestinal microflora. Dietary ABO supplementation is also beneficial to improve immune status and intestinal barrier integrity and microflora of piglets.

Numerous long noncoding RNAs (lncRNAs) are aberrantly expressed in pancreatic cancer (PC); however, their functions and mechanisms in cancer progression are largely unknown. In this study, we identified a novel PC-associated lncRNA, RUNX1-IT1, that was significantly upregulated in PC patient samples from multiple centers and associated with poor prognosis. In vitro and in vivo, alterations in RUNX1-IT1 expression markedly affected PC proliferation, migration and invasion. RUNX1-IT1 contributed to the progression of PC by interacting with the adjacent gene RUNX1. Rescue experiments showed that RUNX1 reduced the cancer-promoting effect of RUNX1-IT1. RNA-seq analysis after silencing RUNX1-IT1 and RUNX1 highlighted alterations in the common target C-FOS. Mechanistically, we demonstrated that RUNX1-IT1 was a trans-acting factor that participated in the proliferation, migration and invasion of PC by recruiting RUNX1 to the C-FOS gene promoter. Furthermore, RUNX1-IT1 enhanced the transcription of the RUNX1 gene, indicating its potential as a cis-regulatory RNA involved in the upstream regulation of RUNX1. Overall, RUNX1-IT1 is a crucial oncogenic lncRNA that activates C-FOS expression by regulating and recruiting RUNX1 and is a potential prognostic biomarker and therapeutic target for PC.

Different dietary nitrogen (N) patterns may have different effects on gut microbiota. To investigate the effects of different crude protein (CP) levels or essential amino acids (EAA) supplementation patterns on the structure and functions of colonic microbiota, 42 barrows (25 ± 0.39 kg) were randomly assigned to 7 dietary treatments including: diet 1, a high CP diet with balanced 10 EAA; diet 2, a medium CP diet with approximately 2% decreased CP level from diet 1 and balanced 10 EAA; diets 3, 4, 5, 6 and 7, low CP diets with 4% decreased CP level from diet 1. Specifically, diet 3 was only balanced for Lys, Met, Thr and Trp; diets 4, 5 and 6 were further supplemented with Ile, Val and Ile + Val on the basis of diet 3, respectively; and diet 7 was balanced for 10 EAA. Results over a 110-d trial showed that reducing the CP level by 2% or 4% dramatically decreased N intake and excretion (P

As a kind of green additive, pectic oligosaccharide (POS) may regulate some physiological functions of animals, such as gut health, antioxidant capacity, immunity and lipid metabolism. This study aimed to identify whether POS administration can improve maternal reproduction, and to determine the possible metabolism. A total of 48 pregnant Wistar rats randomly allotted into 2 groups, and each group was fed a diet supplemented with 0 or 800 mg/kg of POS. Pectic oligosaccharide administration increased rat born number (P

To investigate the influence of different electric shield materials on the temperature distribution in the turbogenerator end region, a 330-MW water–hydrogen–hydrogen-cooled turbogenerator is considered in this paper. Mathematical and physical models of the three-dimensional (3-D) transient electromagnetic field in the turbogenerator end region are established. The magnetic density distribution and the losses of end parts are obtained with different electric shield materials. The loss values obtained from the 3-D transient electromagnetic field calculations with different electric shield materials are applied to the end parts as heat sources. Pressure and fluid velocity values from flow network calculations are applied to the end region as boundary conditions for the fluid and thermal coupling analysis. In addition, a 3-D fluid and thermal coupling model of the turbogenerator end region is established. The distributions of the surface heat transfer coefficient on the inner and outer surfaces of the electric shield are determined with different electric shield materials. Temperature distributions of the stator-end copper winding, finger plate, clamping plate, and electric shield in the turbogenerator end region are investigated with different electric shield materials. The calculated temperature results for the electric shield are compared with measured values, and the calculated results agree well with the measured values.

Synthetic methylotrophy has recently been intensively studied to achieve methanol-based biomanufacturing of fuels and chemicals. However, attempts to engineer platform microorganisms to utilize methanol mainly focus on enzyme and pathway engineering. Herein, we enhanced methanol bioconversion of synthetic methylotrophs by improving cellular tolerance to methanol. A previously engineered methanol-dependent Corynebacterium glutamicum is subjected to adaptive laboratory evolution with elevated methanol content. Unexpectedly, the evolved strain not only tolerates higher concentrations of methanol but also shows improved growth and methanol utilization. Transcriptome analysis suggests increased methanol concentrations rebalance methylotrophic metabolism by down-regulating glycolysis and up-regulating amino acid biosynthesis, oxidative phosphorylation, ribosome biosynthesis, and parts of TCA cycle. Mutations in the O-acetyl-l-homoserine sulfhydrylase Cgl0653 catalyzing formation of l-methionine analog from methanol and methanol-induced membrane-bound transporter Cgl0833 are proven crucial for methanol tolerance. This study demonstrates the importance of tolerance engineering in developing superior synthetic methylotrophs., Wang et al. improve the methanol tolerance for the synthetic methylotroph, Corynebacterium glutamicum. They generate 3 new strains by directed evolution and use biochemical, transcriptomic, and genetic approaches to characterize the pathways underlying the enhanced methanol metabolism. Their findings are important for biomanufacturing purposes.

International audience; Calix[4]arenes have the ability to encapsulate biomimetic guests, offering interesting opportunities to explore their molecular recognition, very close to biological scenarios. In this study, p-sulfonatocalix[4]arene (C4 A) anions and hydrated alkali cations have been used for the in situ recognition of cationic 1,ω-diammonium-alkanes and 1,ω-amino-acids of variable lengths. NMR spectroscopy illustrates that these systems are stable in aqueous solution and the interaction process involves several binding states or stabilized conformations within the C4 A anion, depending of the nature of the guest. DOSY experiments showed that monomeric 1 : 1 host-guest species are present, while the cation does not influence their selfassembly in solution. The folded conformations observed in the solid-state X-ray single-crystal structures shed light on the constitutional adaptivity of flexible chains to environmental factors. Futhermore, a comprehensive screening of 30 single crystal structures helped to understand the in situ conformational fixation and accurate determination of the folded structures of the confined guest molecules, with a compression up to 40 % compared with their linear conformations.

Benzo[a]pyrene (B[a]P) is recognized as a neurotoxic pollutant to mammals, which could impair learning and memory function. Although there is some evidence to suggest that N-methyl-d-aspartate receptor (NMDAR), a glutamate receptor and ion channel protein in nerve cells, is involved into the B[a]P induced neurotoxicity, the exact molecular mechanisms remain to be elucidated, particularly the effects of B[a]P on the NMDAR downstream signaling transduction pathways. In the present study, we examined the neurotoxicity of sub-chronic administrated B[a]P on male Sprague-Dawley rats. Our data suggested that B[a]P exposure caused significant deficits in learning and memory function and the impairment of hippocampal LTP in rats. Further mechanistic studies indicate that B[a]P-induced learning and memory deficits are associated with the inhibition of NMDAR NR1 subunit transcription and protein phosphorylation. More importantly, the inactivation of CaMK II/PKC/PKA-ERK-CREB signaling pathways in hippocampus was detected at both the 2.5 and 6.25 mg/kg B[a]P-treated groups, indicating that multiple targets in NMDAR and downstream signaling pathways are involved in the B[a]P-induced neurotoxicity.

Although the photodimerization of acenaphthylene (ACE) has been known for 100 years, the asymmetric cycloaddition of its 1-substituted derivatives is unknown. Herein, we report a supramolecular photochirogenic approach in which a homochiral and photoactive Δ/Λ-[Pd6 (RuL3 )8 ]28+ metal-organic cage (Δ/Λ-MOC-16) is used as a supramolecular reactor for the enantioselective exited-state photocatalysis of 1-Br-ACE. Owing to preorganization of the substrates by the supramolecular cage, stereochemical control of the triplet state, and nanospace transfer of energy and chirality, the cycloaddition of ACE proceeded with high selectivity for the formation of anti over syn stereoisomers, whereas the regio-, stereo-, and enantioselective cycloaddition of unsymmetrical 1-Br-ACE showed effective enantiodifferentiation of a pair of anti head-to-head stereoisomers. The enzyme-mimicking photocatalysis was verified by catalytic turnover, rate enhancement, and competing-guest inhibition experiments.

To explore the effect of selenium-enriched yeast (SeY) on intestinal barrier functions in weaned pigs upon oxidative stress, a 2×2 factorial design was utilized and thirty-two pigs were randomly assigned into four groups. Pigs with or without exposure to oxidative stress (diquat challenge) were fed with a basal diet or a SeY-containing diet. The trial lasted for 21 days, and result showed that SeY supplementation attenuated body-weight reduction and significantly decreased the serum concentrations of diamine oxidase (DAO) and D-lactic acid in pigs upon diquat challenge (P<0.05). Diquat challenge decreased the villus height and the ratio of villus height to crypt depth (V/C) in the jejunum and ileum (P<0.05). However, SeY supplementation not only elevated the villus height and the ratio of V/C (P<0.05) but also improved the distribution and abundance of tight-junction protein ZO-1 in the jejunum epithelium. Interestingly, SeY supplementation acutely decreased the total apoptosis rate of intestinal epithelial cells in pigs upon diquat challenge (P<0.05). Moreover, SeY elevated the content of antioxidant molecules such as glutathione peroxidase (GSH-Px) and catalase (CAT) but significantly decreased the content of malondialdehyde (MDA) in the intestinal mucosa (P<0.05). Importantly, SeY elevated the expression levels of critical functional genes such as the nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), sodium/glucose cotransporter 1 (SGLT1), and B-cell lymphoma-2 (BCL-2) in the intestinal mucosa upon diquat challenge (P<0.05). Moreover, the expression of caspase-3 was downregulated by SeY in the duodenum and jejunum mucosa (P<0.05). These results indicated that SeY attenuated oxidative stress-induced intestinal mucosa disruption, which was associated with elevated mucosal antioxidative capacity and improved intestinal barrier functions.

Dimer procyanidin B2 [epicatechin-(4β-8)-epicatechin] (PB2) has attracted a lot of interest in nutrition and medicine because of its significant health-promoting abilities. However, the function of PB2 on different types of skeletal myofiber is still unclear. Here, we have found that PB2 significantly increased protein expression of the slow myosin heavy chain (MyHC) and decreased fast MyHC protein in C2C12 myotubes, accompanied by upregulation of mRNA expression of MyHC I, MyHC IIa, and Tnni1 and downregulation of MyHC IIx and MyHC IIb. We have also found that PB2 enhanced the activities of malate dehydrogenase and succinic dehydrogenase and reduced lactate dehydrogenase activity. PB2 promoted phosphorylation of AMPK and significantly increased mRNA expression of AMPKα1. The upstream factors of AMPK, such as phospho-LKB1, NRF1, and CaMKKβ, and the downstream factors of AMPK, including Sirt1 and PGC-1α, were also increased by PB2. Specific suppression of AMPK signaling by AMPKα1 siRNA or by AMPK inhibitor compound C significantly attenuated the PB2-induced upregulation of phospho-AMPK, PGC-1α, and slow MyHC and downregulation of fast MyHC. Our findings suggested that PB2 promotes skeletal slow-twitch myofiber gene expression through the AMPK signaling pathway in C2C12 myotubes.