Discovery and bioinspired total syntheses of unprecedented sesquiterpenoid dimers unveiled bifurcating [4 + 2] cycloaddition and target differentiation of enantiomers.

[4 + 2] cycloaddition has led to diverse polycyclic chiral architectures, serving as novel sources for organic synthesis and biological exploration. Here, an unprecedented class of cadinane sesquiterpene [4 + 2] dimers, henryinins A-E (1-5), with a unique 6/6/6/6/6-fused pentacyclic system, were isolated from Schisandra henryi. The divergent total syntheses of compounds 1-5 and their enantiomers (6-10) were concisely accomplished in eight linear steps using a protection-free approach. Mechanistic studies illustrated the origin of selectivity in the key [4 + 2] cycloaddition as well as the inhibition of reaction pathway bifurcation via desymmetrization. The chemical proteomics results showed that a pair of enantiomers shared common targets (PRDX5 C100 and BLMH C73) and had unique targets (USP45 C588 for 4 and COG7 C419 for 9). This work provides experimental evidence for the discovery of unprecedented cadinane dimers from selective Diels-Alder reaction and a powerful strategy to explore the biological properties of natural products.

Intervention effects of fructooligosaccharide and astragalus polysaccharide, as typical antibiotic alternatives, on antibiotic resistance genes in feces of layer breeding: advantages and defects.

Although antibiotic alternatives are widely used in livestock and poultry breeding industry after in-feed antibiotics ban, their intervention effects on antibiotic resistance genes (ARGs) in these food animals' feces remain poorly understood. Here effects of fructooligosaccharide (FOS) and astragalus polysaccharide (APS), as typical antibiotic alternatives in China, on ARGs in layer feces were estimated by performing metagenomic sequencings and fluorescence quantitative PCR. Fructooligosaccharide significantly reduced sum abundance of ARGs and mobile genetic elements (MGEs) by increasing Lactobacillus clones and reducing Escherichia clones which had relatively higher abundances of ARG subtypes and MGE subtypes in layer feces. However, at least parts of core ARGs and MGEs categories were not reduced by FOS, such as aminoglycosides- and tetracyclines-resistant genes, Tn916, Integrase, and so on. MGEs and microbiome, especially Escherichia genus and Lactobacillus genus, were the key factors affecting ARGs' sum abundance. MGEs had a higher correlation coefficient with ARGs' sum abundance than Escherichia genus and Lactobacillus genus. These findings firstly reveal the defects of antibiotic alternatives in controlling bacterial resistance in livestock and poultry breeding after in-feed antibiotics ban, and more strategies are needed to control pollutions and risks of core ARGs and MGEs in food animals' feces under a special environment.

Heavy metal contamination in Shanghai agricultural soil.

As heavy metals in soil could enrich in biomass and pose health risk to human, it is vital to monitor their contaminations to ensure qualified agricultural production. In this study, we collected >4000 soil samples from agricultural fields in Shanghai during 2010∼2020, and unveiled heavy metal contamination status in this metropolitan. We found that although Shanghai has a long industrialization history, the heavy metal levels in agricultural soil are within safe ranges according to national standard. Specifically, the median levels of Cd, Hg, As, Pb, Cr and Cu are 0.11, 0.13, 7.47, 23.80, 41.00 and 28.30 mg/kg, respectively, which are as good as, or even better than national averages. However, there are spatial and temporal heterogeneities for heavy metal contaminations in Shanghai. For example, the levels of Cd, Hg and Cr are relatively higher in some districts with high industry density, which should be further monitored in the future. Moreover, while the levels for Cd, Cr and Pb have decreased, the level for Hg has mildly increased during this period which needs counteractive measures. Correlation analysis of heavy metal levels and soil fertility parameters suggested overuse of fertilizers may be related to heavy metal contamination in some regions. In summary, our study present by far the largest and most comprehensive landscape of heavy metal contamination in Shanghai agricultural soil, which will be useful for future policy-design and land use planning to ensure safe agricultural production.

Pleiotropic melatonin-mediated responses on growth and cadmium phytoextraction of Brassica napus: A bioecological trial for enhancing phytoremediation of soil cadmium.

Melatonin (MT) has recently gained significant scientific interest, though its mechanism of action in enhancing plant vigor, cadmium (Cd) tolerance, and Cd phytoremediation processes are poorly understood. Therefore, here we investigated the beneficial role of MT in improving growth and Cd remediation potential of rapeseed (Brassica napus). Plants, with or without MT (200 µM L-1), were subjected to Cd stress (30 mg kg1). Without MT, higher Cd accumulation (up to 99%) negatively affected plant growth and developmental feature as well as altered expression of several key genes (DEGs) involved in different molecular pathways of B. napus. As compared to only Cd-stressed counterparts, MT-treated plants exhibited better physiological performance as indicated by improved leaf photosynthetic and gaseous exchange processes (3-48%) followed by plant growth (up to 50%), fresh plant biomass (up to 45%), dry plant biomass (up to 32%), and growth tolerance indices (up to 50%) under Cd exposure. MT application enhanced Cd tolerance and phytoremediation capacity of B. napus by augmenting (1) Cd accumulation in plant tissues and its translocation to above-ground parts (by up to 45.0%), (2) Cd distribution in the leaf cell wall (by up to 42%), and (3) Cd detoxification by elevating phytochelatins (by up to 8%) and metallothioneins (by upto 14%) biosynthesis, in comparison to Cd-treated plants. MT played a protective role in stabilizing hydrogen peroxide and malondialdehyde levels in the tissue of the Cd-treated plants by enhancing the content of osmolytes (proline and total soluble protein) and activities of antioxidant enzymes (SOD, CAT, APX and GR). Transcriptomic analysis revealed that MT regulated 1809 differentially expressed genes (828 up and 981 down) together with 297 commonly expressed DEGs (CK vs Cd and Cd vs CdMT groups) involved in plant-pathogen interaction pathway, protein processing in the endoplasmic reticulum pathway, mitogen-activated protein kinase signaling pathway, and plant hormone signal transduction pathway which ultimately promoted plant growth and Cd remediation potential in the Cd-stressed plants. These results provide insights into the unexplored pleiotropic beneficial action of MT in enhancing in the growth and Cd phytoextraction potential of B. napus, paving the way for developing Cd-tolerant oilseed crops with higher remediation capacity as a bioecological trial for enhancing phytoremediation of hazardous toxic metals in the environment.

Factors influencing the bone mineral density in Duroc boars.

BACKGROUND: Leg weakness affects animal welfare and is one of the primary reasons for culling of boars. Low bone mineral density (BMD) is one of the primary factors contributing to leg weakness. Low BMD also appeared to be associated with severe bone pain and has the highest risk of skeletal fragility. Surprisingly, few studies have been performed on the factors influencing BMD in pigs. Therefore, the primary aim of this study was to identify the influencing factors on boar BMD. Herein, the BMD data were determined through the use of ultrasonography from 893 Duroc boars. Logistic regression model was utilized in the analysis of BMD, in which the explanatory variables in the model were lines, ages, body weights, backfat thicknesses and serum mineral element concentrations (Ca, P, Mg, Cu, Fe, Zn, Mn, Se, Pb and Cd). RESULTS: Results showed that factors significantly influencing BMD included serum Ca, P concentrations, ages and backfat thicknesses (P < 0.05), in which serum Ca concentrations were positively correlated with BMD (P < 0.01), whereas increasing concentrations of serum P decreased BMD (P < 0.01). The serum Ca/P ratio showed significant quadratic effects on BMD (r = 0.28, P < 0.01), and the Ca/P ratio to achieve the best BMD was determined to be 3.7. Furthermore, BMD also changed with age quadratically (r = 0.40, P < 0.01), and reached a peak value around 47 months. Interestingly, a quadratic (r = 0.26, P < 0.01) increase in the BMD was observed as backfat thickness increased, and the inflection point was calculated at around 17 mm. CONCLUSION: In conclusion, BMD characteristics of boars could be detected by ultrasonic method, and serum Ca, serum P, age, and backfat thickness contributed to the greatest effect on BMD.

Optimizing feeding regimen of replacement gilts to improve their reproductive performance and retention rate of their first 2 parities.

The effects of age, body weight (BW), and backfat thickness (BF) of replacement gilts at first estrus and first mating on their subsequent reproductive performance and retention of their first 2 parities as sows was evaluated. A total of 3,025 Danish replacement gilts were categorized by farm (allocated to 4 farms), cross combination, age, BW and BF at first estrus and first mating, estrous cycle number at first mating, and flush feeding before first mating. The result shows that all the factors mentioned above were significantly associated with reproductive performance and retention rates of the first 2 parities. Farm 3 had more piglets born alive per litter (BA) (P < 0.05). Farms 3 and 4 had more healthy piglets per litter (HP) (P < 0.05). Farm 4 had the most piglets weaned per litter (PW) (P < 0.05). Landrace × Landrace × Yorkshire (L × L × Y) replacement gilts had the most total piglets born per litter (TB), BA, HP, PW and a higher retention rate of the 2 parities than Landrace × Yorkshire (L × Y) replacement gilts (P < 0.05). In addition, flush feeding before first mating had the most TB, BA, HP, PW, and a higher retention rate of the 2 parities than no flush feeding (P < 0.05). Because the effects of replacement gilts rearing parameters on reproductive performance traits differed, we used 100 replacement gilts as a unit and the total number of weaned piglets from the first 2 parities as a new index. Replacement gilts undergoing their first estrus between 180 and 210 d of age at 115 to 124.9 kg BW and 14 to 15 mm BF had significantly higher reproductive indexes for their first 2 parities per 100 replacement gilts. Replacement gilts that mated between 210 and 230 d of age at 140 to 149.9 kg BW and 15 to 16 mm BF had optimal reproductive indexes. These results provide a new insight into the complex relationships among these reproductive performance traits and may help guide successful management of replacement gilts as a pivotal starting point for future fertility and longevity of rearing herds.

Diallyl Trisulfide Promotes Placental Angiogenesis by Regulating Lipid Metabolism and Alleviating Inflammatory Responses in Obese Pregnant Mice.

The placental tissue serves as an exchanger between the mother and the fetus during pregnancy in mammals. Proper placental angiogenesis is central to the health of both the mother and the growth and development of the fetus. Maternal obesity is associated with impaired placental function, resulting in restricted placental blood vessel development and fetal developmental disorders. Hydrogen sulfide (H2S) is a ubiquitous second messenger in cells that has many biological effects such as promoting angiogenesis, anti-inflammation, anti-oxidation and promoting lipid metabolism. However, in the case of maternal obesity, whether H2S can be used as an important signaling molecule to regulate body metabolism, alleviate placental inflammation levels and promote placental angiogenesis is still unclear. In this study, diallyl trisulfide (DATS), which is a well-known H2S donor, was derived from garlic and used to treat obese pregnant mice induced by a high-fat diet, to determine its effects on lipid metabolism and inflammation, as well as placental morphology and placental angiogenesis. Here, we show that DATS treatment increased litter size and alive litter size. DATS improved the H2S level in the serum and placenta of the mice. In addition, DATS treatment improved insulin resistance and lipid metabolism, reduced the inflammatory response and alleviated placental vascular dysplasia caused by obesity in obese mice. In summary, our research revealed that H2S is an important signaling molecule in vivo, which can regulate placental angiogenesis and improve the reproductive performance in maternal obesity. The addition of H2S donor DATS during pregnancy promoted placental angiogenesis by regulating lipid metabolism and alleviating inflammatory responses in obese pregnant mice.

Effects on the Cell Barrier Function of L-Met and DL-HMTBA Is Related to Metabolic Characteristics and m6A Modification.

Methionine is a substrate for protein synthesis and participates in many other biological events via its metabolism. We have previously demonstrated significant differences in the metabolism of L-methionine (L-Met) and its precursor DL-2-hydroxy-4-methylthiobutyric acid (DL-HMTBA) in IPEC-J2 cells. When DL-HMTBA is added to the diet, intracellular methionine (Met) sources also contain the natural form of L-Met. Then, what is the effect on Met metabolism when these two Met sources exist simultaneously? Moreover, the effects of metabolic differences on cell function remain unclear. In this study, it was found that when the proportion of L-Met to DL-HMTBA was ≤ 40%:60%, Met transmethylation was promoted and when the proportion of L-Met to DL-HMTBA was ≤ 85%:15%, Met trans-sulfuration and regeneration were improved. In addition, DL-HMTBA improved the cell barrier function when the ratio of L-Met to DL-HMTBA was ≤ 40%:60%. This finding may be due to the decrease in the proportion of S-adenosylmethionine to S-adenosylhomocysteine and mRNA N 6-methyladenosine (m6A) levels, which increase the mRNA stability and protein expression of tight junction zona occludens-1. To sum up, the effects of L-Met and DL-HMTBA on Met metabolism, especially transmethylation, suggest that DL-HMTBA has the potential to influence the intestinal barrier function of animals through epigenetic processes.

Harnessing Natural Products by a Pharmacophore-Oriented Semisynthesis Approach for the Discovery of Potential Anti-SARS-CoV-2 Agents.

Natural products possessing unique scaffolds may have antiviral activity but their complex structures hinder facile synthesis. A pharmacophore-oriented semisynthesis approach was applied to (-)-maoelactone A (1) and oridonin (2) for the discovery of anti-SARS-CoV-2 agents. The Wolff rearrangement/lactonization cascade (WRLC) reaction was developed to construct the unprecedented maoelactone-type scaffold during semisynthesis of 1. Further mechanistic study suggested a concerted mechanism for Wolff rearrangement and a water-assisted stepwise process for lactonization. The WRLC reaction then enabled the creation of a novel family by assembly of the maoelactone-type scaffold and the pharmacophore of 2, whereby one derivative inhibited SARS-CoV-2 replication in HPA EpiC cells with a low EC50 value (19±1 nM) and a high TI value (>1000), both values better than those of remdesivir.

Effects of different amino acid levels and a carvacrol-thymol blend on growth performance and intestinal health of weaned pigs.

BACKGROUND: Over the past years, antibiotic growth promoter had been restricted in animal husbandry production in many countries because of antimicrobial resistance and foodborne antibiotic residues. However, the problems of poor intestinal health and low growth efficiency of piglets have not been solved completely in an antibiotic-free diet, and it is urgent to explore alternatives to antimicrobial growth promoters. METHODS: Here, a total of 532 weaned pigs were assigned to one of 4 treatments, the low amino acid (AA) level diet (d 1 to d 14 is 1.35%, d 15 to d 42 is 1.25%) (Low AA), the low AA level diet supplementation with a carvacrol-thymol blend (50 mg carvacrol and 50 mg thymol/kg of diet) (CB) (Low AA+CB), the high AA level diet (d 1 to d 14 is 1.50%, d 15 to d 42 is 1.40%) (High AA), and the high AA level diet supplementation with a CB (High AA+CB), respectively. Then we measured growth performance and intestinal health indicators of weaned pigs. RESULTS: Results showed that high AA level significantly reduced plasma urea nitrogen, plasma Interleukin-6 (IL-6) and fecal lipocalin-2 contents (P <  0.05), significantly increased the relative abundance of fecal Lactobacillus and Enterococcus, and had a trend to increase the fecal secretory immunoglobulin A (sIgA) and mucin 2 (MUC 2) contents (P <  0.05) in piglets, thereby alleviating the diarrhea of piglets and reducing the feed conversion ratio (FCR) of piglets during d 1~14 after weaning. Dietary supplementation with CB significantly increased the activity of plasma antioxidant enzymes T-SOD and GSH-px (P <  0.05), while significantly reduced plasma malondialdehyde (MDA), plasma interleukin-1ß (IL-1ß), plasma endotoxin and D-lactic acid contents (P <  0.05). Meanwhile, CB significantly decreased fecal lipocalin-2 contents and the abundance of fecal Escherichia coli (P < 0.05). Thus, we hypothesis that dietary supplementation with CB significantly increased the average daily gain (ADG) of piglets (P < 0.05) during d 1~14 after weaning through promoting intestinal health. CONCLUSION: These results suggest that high AA level and dietary supplementation with CB improved the growth performance of weaned pigs in an antibiotic-free diet by improving AA metabolism and intestinal antioxidant capacity.

Circulating Exosomal miR-221 from Maternal Obesity Inhibits Angiogenesis via Targeting Angptl2.

Maternal obesity disrupts both placental angiogenesis and fetus development. However, the links between adipocytes and endothelial cells in maternal obesity are not fully understood. The aim of this study was to characterize exosome-enriched miRNA from obese sow's adipose tissue and evaluate the effect on angiogenesis of endothelial cells. Plasma exosomes were isolated and analyzed by nanoparticle tracking analysis (NTA), electron morphological analysis, and protein marker expression. The number of exosomes was increased as the gestation of the sows progressed. In addition, we found that exosomes derived from obese sows inhibited endothelial cell migration and angiogenesis. miRNA detection showed that miR-221, one of the miRNAs, was significantly enriched in exosomes from obese sows. Further study demonstrated that exosomal miR-221 inhibited the proliferation and angiogenesis of endothelial cells through repressing the expression of Angptl2 by targeting its 3' untranslated region. In summary, miR-221 was a key component of the adipocyte-secreted exosomal vesicles that mediate angiogenesis. Our study may be a novel mechanism showing the secretion of "harmful" exosomes from obesity adipose tissues causes placental dysplasia during gestation.

3-Hydroxy-4-methyldecanoic Acid-Containing Cyclotetradepsipeptides from an Endolichenic Beauveria sp.

An investigation of an endolichenic Beauveria sp. led to the discovery of seven new cyclotetradepsipeptides, beauveamides A-G (2-8), along with the known beauverolide Ka (1). All incorporate a 3-hydroxy-4-methyldecanoic acid (HMDA) moiety in their structures. Their configuration was determined through Marfey's, J-based configuration analysis, and NMR computational methods, representing the first time that the stereostructures of HMDA-moiety-containing cyclotetradepsipeptides have been established. Compounds 1 and 2 exhibited protecting effects on HEI-OC1 cells at 10 µM, while 1, 4, and 5 could stimulate glucose uptake in cultured rat L6 myoblasts at 50 µM. Compound 1 showed dose-dependent activity in both L6 myoblasts and myotubes.

Targeting ubiquitin conjugating enzyme UbcH5b by a triterpenoid PC3-15 from Schisandra plants sensitizes triple-negative breast cancer cells to lapatinib.

Increasing evidence suggested that a number of ubiquitin enzymes, including ubiquitin-activating enzymes, ubiquitin-conjugating enzymes, E3 ubiquitin ligases and deubiquitination enzymes contribute to therapeutic resistance in triple-negative breast cancer (TNBC) cells. Inhibition of these enzymes with small molecule inhibitors may restore therapeutic sensitivity. Here, we demonstrated ubiquitin conjugating enzyme UbcH5b strongly supports HECTD3 auto-ubiquitination in vitro. Based on this, we developed a Fluorescence Resonance Energy Transfer (FRET) assay and identified three Schisandraceae triterpenoids, including PC3-15, to block HECTD3/UbcH5b auto-ubiquitination. Furthermore, we revealed that PC3-15 directly binds to UbcH5b and also inhibits UbcH5b-mediated p62 ubiquitination. We found that the UbcH5b-p62 axis confers TNBC cells resistance to lapatinib by promoting autophagy. Consistently, PC3-15 inhibits lapatinib-induced autophagy and increases lapatinib sensitivity in TNBC in vitro and in mouse xenografts. These findings suggest that the UbcH5b-p62 axis provides potential therapeutic targets and that Schisandraceae triterpenoids may be used for TNBC treatment in combination with lapatinib.

Preparation and Preliminary Evaluation of Dual-functional Nanoparticles for MRI and siRNA Delivery.

In order to improve the transfection efficiency of gene vectors and monitor the effect of gene therapy, this study prepared a drug delivery vector with dual functions. The thiourea reaction was used to synthesize polyethyleneimine (PEI, MW: 1.8 kDa) with superparamagnetic iron oxide nanoparticles (SPION) (PEI1800-SPION), and the lipid polycationic gene vector PEI1800-SPION loaded cationic liposome (LP-PEI1800-SPION) was further prepared by ethanol injection method. Agarose gel electrophoresis experiment, cytotoxicity experiment, and In-vitro gene silencing experiment were used to evaluate the vector and screen the optimal prescription of LP-PEI1800-SPION/siRNA. When the weight ratio of LP-PEI1800-SPION to siRNA is 20, the transfection efficiency of the nanoparticles was the highest, and the silencing efficiency of the target protein was the largest. The cytotoxicity of LP-PEI1800-SPION was low; when the concentration was in the range of 1-50 µg/mL, the survival rate of the four types of cells was above 80%. Prussian blue staining experiments and In-vitro MRI imaging experiments showed that cells had significant uptake and imaging capabilities for LP-PEI1800-SPION. In conclusion, the visualized polycationic lipid siRNA delivery vehicle (LP-PEI1800-SPION) was successfully prepared in this experiment, which provides a research basis for further theranostics of liver cancer.

Chaetolactam A, an Azaphilone Derivative from the Endophytic Fungus Chaetomium sp. g1.

Chaetolactam A (1), an unprecedented azaphilone derivative bearing a unique 9-oxa-7-azabicyclo[4.2.1]octan-8-onering system, together with two new compounds, 11-epi-chaetomugilide B (2) and chaetomugilide D (3) was isolated from an endophytic fungus, Chaetomium sp. g1. Notably, extensive NMR data analyses, NMR calculations with DP4 and DP4+ analyses, ECD calculations, and the RDC method were employed to establish the structure of 1. Furthermore, 2 exhibited potent apoptosis induction activity by mediating caspase-3 activation and PARP degradation at 3 µM in HL-60.

Effects of Dietary Lysine Levels on Production Performance and Milk Composition of High-Producing Sows during Lactation.

Modern genotype sows require enhanced nutrition because of their larger body size and higher reproductive performance than 20 years ago. This study aimed to evaluate the effect of dietary Lys on the lactating of primiparous sows and the second lactating period to minimize sow body weight (BW) loss and maximize the survival rate of piglets and litter gain. A total of 160 primiparous Yorkshire sows were randomly allotted to one of four experimental lactation diets. Formulated to contain 0.84%, 0.94%, 1.04%, and 1.14% standardized ileal digestibility (SID) Lys and balanced in Met, Thr, Trp, and Val. No dietary effects were found on sow body weight (BW) and backfat thickness (BF) change and feed intake during lactation. However, the Lys intake (p = 0.04) of lactation increased linearly with increasing dietary Lys levels. In addition, 1.14% Lys for primiparous sow and 0.94% Lys for second parity sow during lactation increased the survival rate (p = 0.04), weight (p = 0.04), and ADG of piglets at d 21 (p = 0.03). The dietary Lys level did not affect colostrum compositions. However, the dry matter (p = 0.04) and protein (p = 0.03) in milk increased linearly with the increase in dietary Lys levels, whereas moisture decreased linearly (p = 0.05). The level of plasma urea nitrogen (PUN) also increased at d 21 of weaning (p = 0.04). These results indicate that high-yielding lactating sows required 1.14% SID Lys during parity 1, and 0.94% SID Lys during parity 2 to maximize the survival rate of piglets and litter gain, respectively. Moreover, the effects of dietary amino acid (AA) on the production performance of weaning pigs could be mediated through milk composition change.

Pennisetum giganteum: An emerging salt accumulating/tolerant non-conventional crop for sustainable saline agriculture and simultaneous phytoremediation.

Soil salinity is a global threat to the environmental sustainability, in particular to the developing countries due to their limited resources for soil reclamation. In a greenhouse pot experiment, Pennisetum giganteum, was investigated for its tolerance to salt stress and simultaneous phytoremediation capability. 4 weeks post-germination, NaCl (10, 50, 150, 250, 350, 450 and 550 mM) and tap water (control) was applied after every 2 consecutive days for two weeks in a completely randomized design and their effects were established in the growth and physico-chemical aspects of these plants. Our results indicated that P. giganteum withstood high salt stress (with 550 mM NaCl tolerance threshold level). Interestingly, the plants grown under saline conditions had higher biomass yield when compared to the control. Furthermore, the antioxidant activity and proline content of plants under saline conditions were significantly (p < 0.05) higher than those of control plants, indicating their adaptability to high salt stress. Biochemical analysis such as chlorophyll contents, total soluble sugar, total phenol and protein contents revealed considerable differences between plants grown under higher NaCl stress compared to the control conditions. Additionally, significantly different ionic flux along with high K+/Na+ ratio was observed in plants grown under a range of saline conditions. The results obtained are therefore of value to indicate P. giganteum an eco-friendly alternate source for the phytoremediation of saline soils and may be used as base for future research on this plant. Effective strategies need to be adopted with this plant to reclaim saline-degraded as well as marginal soils.

Effect of Sows Gestational Methionine/Lysine Ratio on Maternal and Placental Hydrogen Sulfide Production.

The placenta is a unique bond between the mother and the fetus during pregnancy, and a proper placental angiogenesis is vital for fetal development. H2S is an endogenous stimulator of angiogenesis that is mainly produced by the methionine transsulfurationpathway. The goal of this study was to evaluate the effect of gestational dietary methionine on maternal and placental H2S production in sows. Multiparous sows (Large×White; third parity; n = 65) were randomly allocated into five groups, with feed diets comprisingstandardized ileal digestible methionine/lysine (Met/Lys) ratios of 0.27 (nutrient requirements of swine (NRC); 2012 level), 0.32, 0.37, 0.42, and 0.47, respectively. The litter size and weight at birth were measured and recorded. Maternal blood samples were obtained at embryonic day (E) E40 d, E90 d, and E114 d of gestation. The placental samples were collected at parturition. The results showed that maternal plasma H2S concentration was not affected at E40 d. However, the maternal plasma H2S concentration changed quadratically with the dietary Met/Lys ratio at E90 d (p < 0.01) and E114 d (p = 0.03). The maximum maternal plasma H2S concentration was at the dietary Met/Lys ratio of 0.37. Meanwhile, maternal plasma H2S concentration was positively correlated with piglets born alive (p < 0.01) and litter weight (p < 0.01). Consistent with the maternal plasma, the placental H2S concentration also changed quadratically with the dietary Met/Lys ratio (p = 0.03); the Met/Lys ratio of 0.37 showed the maximum H2S concentration. In conclusion, our findings revealed that the gestational dietary Met/Lys ratio could affect maternal and placental H2S concentrations, which may be an important molecular mechanism affecting placental angiogenesis and piglet development.

Oxidative Stress and Inflammation in Sows with Excess Backfat: Up-Regulated Cytokine Expression and Elevated Oxidative Stress Biomarkers in Placenta.

In sows, excess backfat during late gestation is associated with increased farrowing difficulties and influences the fetus, but the impact of backfat thickness on placental inflammation, oxidative stress, and vascular development has not been defined. In this study, 120 sows were divided into six groups based on backfat thickness (≤16, 17-18, 19-20, 21-22, 23-24, and ≥25 mm) in late gestation. The placental lipids, reactive oxygen species (ROS), malondialdehyde (MDA), and total antioxidant capacity (TAC) levels, inflammatory-related cytokine and angiogenesis were determined. The concentrations of triglycerides, total cholesterol, low density lipoprotein cholesterol (LDL-C), and free fatty acid (FFA) linearly increased (p < 0.05) associated with increased late gestation backfat. ROS and MDA increased and TAC decreased (p < 0.05) as the backfat thickness increased. The mRNA expression of toll-like receptors (TLR) 2, TLR4, tumor necrosis factor (TNF) α, interleukin (IL)-1ß, IL-6, and monocyte chemoattractant protein (MCP)-1 increased with increased backfat in late gestation. There were no differences in IL-8 and IL-10 mRNA expression among sows with different backfat thickness. Placental vessel density initially increased and then decreased with increasing backfat thickness of sows. Similarly, the mRNA levels of vascular endothelial growth factor (VEGF) were also increased and then decreased. Excessive backfat in late gestation was associated with greater oxidative stress, greater expression of proinflammatory cytokines, and decreased expression of placental angiogenic regulators.

Maternal Eicosapentaenoic Acid Feeding Decreases Placental Lipid Deposition and Improves the Homeostasis of Oxidative Stress Through a Sirtuin-1 (SIRT1) Independent Manner.

SCOPE: Maternal obesity has been associated with increased placental lipotoxicity and impaired mitochondrial function. Sirtuin-1 (SIRT1) is an important regulator of both lipid metabolism and mitochondrial biogenesis. The present study aims to determine whether supplementation of the maternal diet with eicosapentaenoic acid (EPA) can decrease placental lipid deposition and improve antioxidant ability, in a SIRT1-dependent manner. METHODS AND RESULTS: Pregnant SIRT1+/- mice (mated with male SIRT1+/- ) are fed a high-fat diet consisting of 60% of the kcal from fat, or an equienergy EPA diet for 18.5 d. Supplementation with EPA significantly changes maternal plasma, placental and fetal fatty acid composition, and decreases placental and fetal lipid content. In addition, placental antioxidant capacity and lipid peroxidation products are increased, placental uncoupling protein 1 (UCP1) and PPARγ coactivator-1 α (PGC1α) expression are activated, and mitochondrial swelling decreases. While SIRT1 deficiency has little effect on placental fatty acid composition and lipid content, decreased fetal lipid deposition is observed, placental PGC1α expression decreases, mitochondrial swelling increases, and placental total superoxide dismutase (T-SOD) activity increases. Both EPA and SIRT1 have no effect on BODIPY-FL-C16 uptake. Interestingly, there is no significant interaction between diet and genotype. CONCLUSION: Maternal EPA feeding decreases placental lipid deposition and improves placental oxidative stress homeostasis independent of SIRT1.