Arginine alleviates Clostridium perfringens α toxin-induced intestinal injury in vivo and in vitro via the SLC38A9/mTORC1 pathway.

Introduction: Clostridium perfringens α toxin is a main virulence factor responsible for gut damage in animals. Arginine is a functional amino acid exhibiting significant immunoregulatory activities. However, the effects and immunoregulatory mechanisms of arginine supplementation on α toxin-induced intestinal injury remain unclear. Methods: In vivo, 256 male Arbor Acres chickens were randomly assigned to a 2×2 factorial arrangement, involving diet treatments (with or without 0.3% arginine supplementation) and immunological stress (with or without α toxin challenge). In vitro, IEC-6 cells were treated with or without arginine in the presence or absence of α toxin. Moreover, IEC-6 cells were transfected with siRNA targeting mTOR and SLC38A9 to explore the underlying mechanisms. Results and discussion: The results showed that in vivo, arginine supplementation significantly alleviated the α toxin-induced growth performance impairment, decreases in serum immunoglobulin (Ig)A and IgG levels, and intestinal morphology damage. Arginine supplementation also significantly reduced the α toxin-induced increase in jejunal proinflammatory cytokines interleukin (IL)-1ß, IL-6 and IL-17 mRNA expression. Clostridium perfringens α toxin significantly decreased jejunal mechanistic target of rapamycin (mTOR) and solute carrier family 38 member 9 (SLC38A9) mRNA expression, while arginine supplementation significantly increased mTOR and SLC38A9 mRNA expression. In vitro, arginine pretreatment mitigated the α toxin-induced decrease in cell viability and the increase in cytotoxicity and apoptosis. Arginine pretreatment also alleviated the α toxin-induced upregulation of mRNA expression of inflammation-related cytokines IL-6, C-X-C motif chemokine ligand (CXCL)10, CXCL11 and transforming growth factor-ß (TGF-ß), as well as apoptosis-related genes B-cell lymphoma-2 associated X protein (Bax), B-cell lymphoma-2 (Bcl-2), B-cell lymphoma-extra large (Bcl-XL) and cysteinyl aspartate specific proteinase 3 (Caspase-3) and the ratio of Bax to Bcl-2. Arginine pretreatment significantly increased the α toxin-induced decrease in mTOR, SLC38A9, eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4EBP1) and ribosomal protein S6 kinase (S6K) mRNA expression. Knockdown SLC38A9 and mTOR largely abrogated the positive effects of arginine pretreatment on α toxin-induced intracellular changes. Furthermore, SLC38A9 silencing abolished the increased mTOR mRNA expression caused by arginine pretreatment. In conclusion, arginine administration attenuated α toxin-induced intestinal injury in vivo and in vitro, which could be associated with the downregulation of inflammation via regulating SLC38A9/mTORC1 pathway.

Liver and Muscle Transcriptomes Differ in Mid-Lactation Cows Divergent in Feed Efficiency in the Presence or Absence of Supplemental Rumen-Protected Choline.

Improving dairy cow feed efficiency is critical to the sustainability and profitability of dairy production, yet the underlying mechanisms that contribute to individual cow variation in feed efficiency are not fully understood. The objectives of this study were to (1) identify genes and associated pathways that are altered in cows with high- or low-residual feed intake (RFI) using RNA sequencing, and (2) determine if rumen-protected choline supplementation during mid-lactation would influence performance or feed efficiency. Mid-lactation (134 ± 20 days in milk) multiparous Holstein cows were randomly assigned to either supplementation of 0 g/d supplementation (CTL; n = 32) or 30 g/d of a rumen-protected choline product (RPC; 13.2 g choline ion; n = 32; Balchem Corp., New Hampton, NY, USA). Residual feed intake was determined as dry matter intake regressed on milk energy output, days in milk, body weight change, metabolic body weight, and dietary treatment. The 12 cows with the highest RFI (low feed efficient; LE) and 12 cows with the lowest RFI (high feed efficient; HE), balanced by dietary treatment, were selected for blood, liver, and muscle analysis. No differences in production or feed efficiency were detected with RPC supplementation, although albumin was greater and arachidonic acid tended to be greater in RPC cows. Concentrations of ß-hydroxybutyrate were greater in HE cows. Between HE and LE, 268 and 315 differentially expressed genes in liver and muscle tissue, respectively, were identified through RNA sequencing. Pathway analysis indicated differences in cell cycling, oxidative stress, and immunity in liver and differences in glucose and fatty acid pathways in muscle. The current work indicates that unique differences in liver and muscle post-absorptive nutrient metabolism contribute to sources of variation in feed efficiency and that differences in amino acid and fatty acid oxidation, cell cycling, and immune function should be further examined.

Effects of dietary vitamin K3 supplementation on production performance, egg quality, vitamin K-dependent proteins, and antioxidant properties in breeding geese during the laying period.

The aim of this work was to investigate the effects of dietary vitamin K3 (VK3) supplementation on production performance, egg quality, vitamin K-dependent proteins, and antioxidant properties in breeding geese during the laying period. A total of one hundred twenty 82-wk-old Wulong geese with similar body weights were randomly divided into 6 groups with 4 replicates and 5 geese each (1 male and 4 female). The geese in the control group were fed a basal diet, and the geese in the treatment groups were fed diets supplemented with different levels of VK3 (2.5, 5.0, 7.5, 10.0, and 12.5 mg/kg) for 11 wk. Dietary VK3 supplementation linearly and quadratically increased feed intake, egg mass, egg weight, and egg production (P < 0.05). Increasing VK3 levels linearly and quadratically increased albumen height, shell thickness and Haugh unit of eggs (P < 0.05). VK3 reduced osteocalcin (OC) and uncarboxylated osteocalcin (ucOC) levels in the serum. Dietary VK3 addition linearly decreased serum malondialdehyde (MDA) levels (P < 0.01). There was linear and quadratic effect in the activity of serum total superoxide dismutase (T-SOD) (P < 0.01), and linear effect in serum total antioxidant capacity (T-AOC) (P < 0.01). In conclusion, dietary VK3 supplementation enhanced the production performance, egg quality, vitamin K-dependent proteins, and antioxidant properties in breeding geese during the laying period. The optimal dose of dietary VK3 supplementation was 10.0 mg/kg.

Effects of dietary arginine supplementation on production performance, serum biochemicals, antioxidant capacity, and immunity of laying Wulong geese.

This study investigated the effects of dietary arginine supplementation on the production performance, serum biochemicals, antioxidant capacity, and immunity of laying Wulong geese. A total of 150 Wulong geese (34-wk old) with similar body weights were randomly divided into 6 groups with 5 replicates and 5 geese each (1 male and 4 female). The geese in the control group were fed a corn-rapeseed meal basal diet, and the geese in the treatment groups were fed the basal diet supplemented with 0.1, 0.2, 0.3, 0.4, and 0.5% arginine. The experiment lasted for 17 wk. Our results showed that dietary arginine increased the egg production rate (LR) and average egg weight (AEW) of geese in a quadratic manner (P < 0.05). Dietary arginine had a quadratic effect on the contents of total protein (TP) and triglyceride (TG) (P < 0.05) in the serum. Dietary arginine quadratically decreased the content of malondialdehyde (MDA) and increased the activity of total superoxide dismutase (T-SOD) (P < 0.05). Dietary arginine supplementation linearly and quadratically increased the contents of immunoglobulin A (IgA) and immunoglobulin G (IgG), and linearly increased the content of nitric oxide (NO) (P < 0.05). In conclusion, dietary arginine supplementation can significantly improve the production performance, serum biochemicals, antioxidant capacity, and immunity of laying Wulong geese. Therefore, 0.3% arginine (actual content: 1.02%) is recommended in the diet.

NIR-II-absorbing diimmonium polymer agent achieves excellent photothermal therapy with induction of tumor immunogenic cell death.

Photothermal therapy has shown great promise for cancer treatment and second near-infrared (NIR-II) -absorbing particles could further improve its precision and applicability due to its superior penetration depth and new imaging ability. Herein, high NIR-II-absorbing polymer particles were prepared by using soluble isobutyl-substituted diammonium borates (P-IDI). The P-IDI showed stronger absorption at 1000-1100 nm, which exhibited excellent photostability, strong photoacoustic imaging ability and high photothermal conversion efficiency (34.7%). The investigations in vitro and in vivo demonstrated that the excellent photothermal effect facilitated complete tumor ablation and also triggered immunogenic cell death in activation of the immune response. The high solubility and excellent photothermal conversion ability demonstrated that polymer IDI particles were promising theranostic agents for treatment of tumors with minor side effects.

Nicotinamide Adenine Dinucleotide Precursor Suppresses Hepatocellular Cancer Progression in Mice.

Targeting Nicotinamide adenine dinucleotide (NAD) metabolism has emerged as a promising anti-cancer strategy; we aimed to explore the health benefits of boosting NAD levels with nicotinamide riboside (NR) on hepatocellular carcinoma (HCC). We established three in vivo tumor models, including subcutaneous transplantation tumor model in both Balb/c nude mice (xenograft), C57BL/6J mice (allograft), and hematogenous metastatic neoplasm in nude mice. NR (400 mg/kg bw) was supplied daily in gavage. In-situ tumor growth or noninvasive bioluminescence were measured to evaluate the effect of NR on the HCC process. HepG2 cells were treated with transforming growth factor-ß (TGF-ß) in the absence/presence of NR in vitro. We found that NR supplementation alleviated malignancy-induced weight loss and metastasis to lung in nude mice in both subcutaneous xenograft and hematogenous metastasis models. NR supplementation decreased metastasis to the bone and liver in the hematogenous metastasis model. NR supplementation also significantly decreased the size of allografted tumors and extended the survival time in C57BL/6J mice. In vitro experiments showed that NR intervention inhibited the migration and invasion of HepG2 cells triggered by TGF-ß. In summary, our results supply evidence that boosting NAD levels by supplementing NR alleviates HCC progression and metastasis, which may serve as an effective treatment for the suppression of HCC progression.

Multiple amino acid supplementations to reduce dietary protein for pigs during early and late finisher periods under commercial conditions.

BACKGROUND: With the easy availability and competitive prices of crystalline amino acids (AAs), the reduction of dietary crude protein (CP) for pigs during early and late finisher periods is possible under commercial conditions. Two experiments were conducted to assess the growth efficiency of early and late-finishing pigs fed with protein-restricted diets supplemented with Lys, Met, Thr, Trp, Val, Ile and His. In Experiment 1, 840 early finishing pigs were allocated to four dietary treatments with CP levels designed at 150, 142, 134, and 126 g kg-1 diet. In Experiment 2, 768 late-finishing pigs were allotted to four dietary treatments providing CP levels at 140, 130, 120, and 110 g kg-1 diet. RESULTS: In Experiment 1, the data showed that CP levels could be decreased from 150 to 126 g kg-1 without adversely affecting performance of early finishing pigs as no significant difference was observed for final bodyweight, average daily gain (ADG), feed to gain ratio (F:G), or average daily feed intake (ADFI). In Experiment 2, late-finishing pigs consuming 120 g kg-1 CP tended to have the highest ADG and lowest F:G whereas those fed the 110 g kg-1 CP diet showed the opposite trend. Based on quadratic analysis, the optimum CP levels to maximize ADG and minimize F:G were 126 and 127 g kg-1 , respectively. CONCLUSION: These findings showed that dietary CP levels could be decreased to 126 g kg-1 for early finishing pigs while improved performance was noted in late-finishing pigs consuming 120 g kg-1 CP. © 2023 Society of Chemical Industry.

Medication rule and mechanism of traditional Chinese medicine in treating metabolism-associated fatty liver disease based on bioinformatics technology / 数字中医药（英文）

@#[Objective[ To analyze the main syndrome types, medication rules, and core prescription characteristics of traditional Chinese medicine (TCM) in the treatment of metabolism-associated fatty liver disease (MAFLD), and to predict the anti-MAFLD mechanism of core formula, so as to provide references for the clinical application of TCM and the development of new drugs. [Methods] Literature research on TCM in treating MAFLD was retrieved from China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang Database since the establishment of the database to July 2022. Excel 2019 and Chinese Medicine Inheritance Computing Platform (V3.0) were used for frequency analysis, association rule analysis, and cluster analysis of effective prescriptions. The key components, targets, and action pathways of anti-MAFLD core formulas were predicted by network pharmacology. Finally, the interactions between the obtained core components and their core targets were verified reversely by molecular docking technology. [Results] A total of 218 articles were screened and selected, including 352 prescriptions, involving 270 traditional Chinese herbs. The drugs were used a total of 3 901 times, and a total of 10 915 cases were collected, among which the prevalence rate was higher in males. The main types of TCM syndrome included intermingled phlegm and blood stasis syndrome, liver depression and spleen deficiency syndrome, and damp-heat in liver and gallbladder syndrome, among which Shanzha (Crataegi Fructus), Danshen (Salviae Miltiorrhizae Radix et Rhizoma), Fuling (Poria), Zexie (Alismatis Rhizoma), Chaihu (Bupleuri Radix), and Baizhu (Atractylodis Macrocephalae Rhizoma) were the most frequently used. The properties of Chinese medicine primarily encompassed thermal characteristics, with a predominant emphasis on cold and warm; the flavors of herbs were predominantly characterized by bitterness and sweetness, while the majority exhibited tropism towards the spleen and liver meridians. The drugs were primarily classified based on their efficacy in tonifying deficiencies, promoting diuresis and moistening, enhancing blood circulation and removing blood stasisheat-clearing, etc. The association rules were employed to derive a set of 20 core drug pairs, while cluster analysis was utilized to identify three distinct groups of core drug combinations. Network pharmacological showed that the main components of the core formula “Shanzha (Crataegi Fructus) - Danshen (Salviae Miltiorrhizae Radix et Rhizoma) - Zexie (Alismatis Rhizoma) - Chaihu (Bupleuri Radix) - Fuling (Poria)” in the treatment of MAFLD were quercetin, apigenin, puerarin, luteolin, ursolic acid, kaempferol, tanshinone IIA, emodin, paeonol, etc., which involved RAC-alpha serine/threonine-protein kinase 1 (AKT1), cellular tumor antigen p53 (TP53), interleukin (IL)-6, IL-1β, signal transducer and activator of transcription 3 (STAT3), epidermal growth factor receptor (EGFR), peroxisome proliferative activated receptor gamma (PPARG), and other key targets. The molecular docking results showed that the core components had good binding to lipid and atherosclerosis, and phosphatidylinositol 3 kinase (PI3K)/AKT signaling pathway-associated proteins. [Conclusion] The main principles of TCM for the treatment of MAFLD involve soothing the liver and strengthening the spleen, eliminating phlegm and dampness, clearing heat and dampness, as well as promoting blood circulation and removing blood stasis. The core formula may exert anti-MAFLD effects mediated through multiple components, targets, and signaling pathways. This study establishes a theoretical foundation for the clinical application of TCM in the treatment of MAFLD, and serves as a reference for further exploration of new drugs against MAFLD.

Optimal dietary standardized ileal digestible lysine level for pigs during the grower, early and late finisher periods.

BACKGROUND: Lysine (Lys) is the first limiting amino acid for pigs fed corn-soybean meal diets. Three experiments were conducted to estimate the optimal standardized ileal digestible (SID) Lys requirement for growing (Exp. 1), early finishing (Exp. 2), and late finishing (Exp. 3) pigs under commercial conditions. RESULTS AND CONCLUSIONS: In Exp. 1, a total of 650 growing pigs (32.21 ± 0.33 kg bodyweight), were allocated to 5 dietary treatments supplemented with 0.75, 0.85, 0.94, 1.03, and 1.13% SID Lys. Each treatment had 5 replicate pens with 26 pigs per pen. The lowest feed to gain ratio (F:G) was obtained by pigs fed the 1.03% Lys diet and F:G showed both a linear and a quadratic response with increasing Lys (P < 0.05). Based on broken-line and quadratic analysis models, dietary SID Lys levels for the minimum F:G were 0.94%. In Exp. 2, 650 finishing pigs (57.24 ± 2.00 kg bodyweight) were allotted to 5 dietary treatments providing SID Lys of 0.63, 0.71, 0.79, 0.87, and 0.95%. Each treatment had 5 replicates, 26 pigs per replication. The highest final bodyweight was achieved by 0.79% Lys while the highest average daily gain (ADG) and average daily feed intake (ADFI) was achieved by pigs consuming the 0.87% Lys diet (P < 0.05). Additionally, the lowest F:G was obtained by pigs fed the 0.79 and 0.87% Lys diet (P < 0.05). Based on broken-line and quadratic analysis models, the optimum Lys was 0.81 and 0.82% for ADG and F:G, respectively. In Exp. 3, 600 late finishing pigs (92.22 ± 2.41 kg bodyweight), were divided into 5 treatments providing Lys levels of 0.53, 0.60, 0.66, 0.73, and 0.79%. Each treatment had 5 replicates, 24 pigs per replication. Results showed that final bodyweight, ADG, ADFI, and F:G was not affected by increasing dietary Lys level, suggesting that the lowest SID Lys (0.53%) was sufficient for this group of pigs. Taken together, the SID Lys requirement for pigs from 30 to 60 kg, 60 to 90 kg, 90 to 120 kg was 0.94%, 0.81 to 0.82, and 0.53%, respectively, depending on the response criteria with performance maximized.

Potential food-drug interaction risk of thymoquinone with warfarin.

Thymoquinone, predominant bioactive compound in Nigella sativa L. (N.sativa) oil, may inhibit the activity of cytochrome P450 2C9 (CYP2C9). However, it is not clear whether thymoquinone can affect the pharmacokinetic behavior of warfarin. Thus, we further to investigate the effect of thymoquinone on warfarin 7-hydroxylation activity and to quantitatively evaluate their food-drug interactions (FDIs) potential. Our data demonstrated that thymoquinone could inhibit warfarin 7-hydroxylase activity with IC50 value of 11.35 ± 0.25 µM. The kinetic analysis indicated that thymoquinone exhibited competitive inhibition on warfarin 7-hydroxylation with Ki value of 3.50 ± 0.44 µM. FDIs risk prediction suggested that coadministration of thymoquinone (>18 mg/day) or dietary supplements containing thymoquinone (N.sativa > 1 g/day or N. sativa oil >1 g/day) might influence pharmacokinetic behavior of warfarin. In conclusion, coadministration of thymoquinone or dietary supplements containing thymoquinone in warfarin-treated patients would likely trigger off unexpected potential drug interactions.

Anticancer effects of herbal medicines in pancreatic ductal adenocarcinoma through modulation of steroid hormone response proteins.

Many individual herbs and herbal formulae have been demonstrated to provide safe and effective treatment for pancreatic ductal adenocarcinoma (PDAC); however, the therapeutic mechanisms underlying their effects have not been fully elucidated. A total of 114 herbal formulae comprising 216 single herbal medicines used to treat PDAC were identified. Cluster analysis revealed a core prescription including four herbs [Glycyrrhizae Radix et Rhizome (Gan Cao), Codonopsis Radix (Dang Shen), Citri Reticulatae Pericarpium (Chen Pi), and Pinelliae Rhizoma (Ban Xia)] in combination to treat PDAC, and 295, 256, 141, and 365 potential targets were screened for each of these four herbs, respectively. PDAC-related proteins (n = 2940) were identified from the DisGeNET database. Finally, 44 overlapping targets of herbs and PDAC were obtained, representing potential targets of the herbal medicines for PDAC treatment. GO enrichment analysis indicated that targets common to herbs and PDAC primarily functioned in response to steroid hormones. KEGG pathway enrichment analysis indicated that the herbs may prevent PDAC by influencing apoptotic, p53, and PI3K/Akt signaling pathways. Further, molecular docking analysis indicated that of identified bioactive compounds, stigmasterol, phaseol, perlolyrine, shinpterocarpin, and licopyranocoumarin have good binding ability with proteins involved in responses to steroid hormones, while stigmasterol, phaseol, perlolyrine, and DIOP have good binding ability with PTGS2(also known as COX-2), ESR1, ESR2, AR, and PGR. The anti-PDAC activity of herbal medicines may be mediated via regulation of proteins with roles in responses to steroid hormones. This study provides further evidence supporting the potential for use of herbal medicines to treat PDAC.

Potential herb-drug interaction risk of thymoquinone and phenytoin.

Thymoquinone is a main bioactive compound of Nigella sativa L. (N.sativa), which has been used for clinical studies in the treatment of seizures due to its beneficial neuroprotective activity and antiepileptic effects. It has been evidenced that thymoquinone may inhibit the activity of cytochrome P450 2C9 (CYP2C9). However, little is known about the effect of thymoquinone or N.sativa on the pharmacokinetic behavior of phenytoin, a second-line drug widely used in the management of status epilepticus. In this study, we systematically investigated the risk of the potential pharmacokinetic drug interaction between thymoquinone and phenytoin. The inhibitory effect of thymoquinone on phenytoin hydroxylation activity by CYP2C9 was determined using UPLC-MS/MS by measuring the formation rates for p-hydroxyphenytoin (p-HPPH). The potential for drug-interaction between thymoquinone and phenytoin was quantitatively predicted by using in vitro-in vivo extrapolation (IVIVE). Our data demonstrated that thymoquinone displayed effective inhibition against phenytoin hydroxylation activity. Enzyme kinetic studies showed that thymoquinone exerted a competitive inhibition against phenytoin hydroxylation with a Ki value of 4.45 ± 0.51 µM. The quantitative prediction from IVIVE suggested that the co-administration of thymoquinone (>18 mg/day) or thymoquinone-containing herbs (N.sativa > 1 g/day or N.sativa oil >1 g/day) might result in a clinically significant herb-drug interactions. Additional caution should be taken when thymoquinone or thymoquinone-containing herbs are co-administered with phenytoin, which may induce unexpected potential herb-drug interactions via the inhibition of CYP2C9.

Effects of zinc and Bacillus subtilis on the reproductive performance, egg quality, nutrient digestion, intestinal morphology, and serum antioxidant capacity of geese breeders.

The effects of zinc (Zn) and Bacillus subtilis (B. subtilis) on reproductive performance, egg quality, nutrient digestion, intestine morphology, and antioxidant capacity were explored in geese breeders. Geese breeders (n = 120, 46-wk of age) were randomly assigned into 6 groups with 4 replicates of 5 birds each (1 male and 4 female). Breeders were fed diets with 2 levels of B. subtilis (2.5 × 109 and 5 × 109 CFU/kg) crossed with three levels of Zn (25, 45, and 65 mg/kg) for duration of 10-wk. The results showed that the egg laying rate (P < 0.05), fertility rate (P < 0.01), hatchability rate (P < 0.05), yolk color (P < 0.05), and the retentions of crude protein (P < 0.05), ether extract (P < 0.05) and phosphorus of geese breeders were improved by dietary supplementation of 5 × 109 CFU/kg B. subtilis and 25 mg or 45 mg/kg Zn. The serum T-SOD (P < 0.05) was increased by 45 mg/kg Zn supplementation. The serum T-AOC (P < 0.05) and retention of Zn (P < 0.05) were increased by 5 × 109 CFU/kg B. subtilis supplementation. The birds fed with 5 × 109 CFU/kg B. subtilis and 25 mg or 45 mg/kg Zn showed improved villus length (P < 0.01) and villus length/ crypt depth (P < 0.01) in both the jejunum and ileum. In conclusion, the combination of B. subtilis and Zn may have synergistic effects on these parameters, and dietary inclusion of 5 × 109 CFU/kg B. subtilis and 45 mg/kg Zn is recommended for improving the reproductive performance of geese breeders.

NAD Supplement Alleviates Intestinal Barrier Injury Induced by Ethanol Via Protecting Epithelial Mitochondrial Function.

BACKGROUND: The epithelial tight junction is an important intestinal barrier whose disruption can lead to the release of harmful intestinal substances into the circulation and cause damage to systemic injury. The maintenance of intestinal epithelial tight junctions is closely related to energy homeostasis and mitochondrial function. Nicotinamide riboside (NR) is a NAD booster that can enhance mitochondrial biogenesis in liver. However, whether NR can prevent ethanol-induced intestinal barrier dysfunction and the underlying mechanisms remain unclear. METHODS: We applied the mouse NIAAA model (chronic plus binge ethanol feeding) and Caco-2 cells to explore the effects of NR on ethanol-induced intestinal barrier dysfunction and the underlying mechanisms. NAD homeostasis and mitochondrial function were measured. In addition, knockdown of SirT1 in Caco-2 cells was further applied to explore the role of SirT1 in the protection of NR. RESULTS: We found that ethanol increased intestinal permeability, increased the release of LPS into the circulation and destroyed the intestinal epithelial barrier structure in mice. NR supplementation attenuated intestinal barrier injury. Both in vivo and in vitro experiments showed that NR attenuated ethanol-induced decreased intestinal tight junction protein expressions and maintained NAD homeostasis. In addition, NR supplementation activated SirT1 activity and increased deacetylation of PGC-1α, and reversed ethanol-induced mitochondrial dysfunction and mitochondrial biogenesis. These effects were diminished with the knockdown of SirT1 in Caco-2 cells. CONCLUSION: Boosting NAD by NR alleviates ethanol-induced intestinal epithelial barrier damage via protecting mitochondrial function in a SirT1-dependent manner.

Effects of dietary nicotinic acid supplementation on meat quality, carcass characteristics, lipid metabolism, and tibia parameters of Wulong geese.

The purpose of this study was to evaluate the effects of nicotinic acid (NA) supplementation on the meat quality, carcass characteristics, lipid metabolism, and tibia parameters in Wulong geese. A total of 360 twenty-nine-day-old Wulong geese were randomly divided into 6 treatments, and each treatment included 6 pens with 10 birds per pen. Birds were fed a basal diet supplemented with 0, 20, 40, 60, 80, or 100 mg/kg NA for 12 wk. Dietary NA supplementation linearly decreased L* value and increased pH and water-holding capacity in the breast muscle (P < 0.05). Increasing NA levels linearly and quadratically decreased shear force of breast muscle (P < 0.001). Dietary NA supplementation linearly reduced the thickness of subcutaneous fat plus the skin and percentage of abdominal fat, and enhanced the width of intermuscular fat band (P < 0.001). Dietary NA addition linearly and quadratically increased intramuscular fat (IMF) content (P ≤ 0.001). Increasing NA levels decreased serum total cholesterol and low-density lipoprotein cholesterol levels and increased serum lipase activity and hepatic mRNA expression of lipoprotein lipase in a linear manner (P < 0.05). There were linear and quadratic effects in serum triglycerides and high-density lipoprotein cholesterol (HDL-C) levels and malate dehydrogenase activity with the NA addition (P < 0.05). Feeding the NA-supplemented-diets linearly increased tibia length, circumference, fat-free dry weight, and ash content (P < 0.001). There were linear and quadratic increases in Ca and P contents with the NA supplementation (P < 0.05). According to the quadratic regression analyses fitted to shear force, IMF content, serum triglycerides and HDL-C levels, and tibial Ca and P contents, the optimal dietary NA supplementation was 80 to 90 mg/kg. In conclusion, NA addition enhanced meat quality and IMF content, regulated lipid metabolism, and increased tibia quality of Wulong geese. The dosage of 80 mg/kg NA in Wulong geese aged 5 to 16 wk was recommended.

Dietary combined supplementation of iron and Bacillus subtilis enhances reproductive performance, eggshell quality, nutrient digestibility, antioxidant capacity, and hematopoietic function in breeder geese.

A 3 × 2 factorial arrangement of treatments was conducted to investigate the effects of iron (Fe, 40, 60, and 80 mg/kg) and Bacillus subtilis (2.5 × 109 and 5.0 × 109 CFU/kg) supplementation on reproductive performance, egg quality, nutrient digestibility, hormone levels, antioxidant indices, and hematological parameters in breeder geese. A total of one hundredtwenty 46-week-old Wulong breeder geese were randomly assigned to 1 of 6 dietary treatments with 4 replicates per treatment and 5 geese per replicate for 10 wk following 1 wk of adaption. Dietary Fe supplementation increased egg weight (P = 0.036), fertility (P = 0.022), serum total antioxidant capacity (P = 0.022), red blood cell (P = 0.001), hematocrit (HCT, P < 0.001), hemoglobin (HGB, P = 0.005), and mean corpuscular volume (MCV, P < 0.001). Dietary B. subtilis supplementation increased egg production (P = 0.025), eggshell thickness (P = 0.020), apparent phosphorus digestibility (P < 0.001), serum follicle stimulating hormone (P = 0.043), total antioxidant capacity (P < 0.001), HCT (P < 0.001), HGB (P < 0.001), and MCV (P = 0.025), and reduced malondialdehyde level (P = 0.008). The birds fed diets supplemented with 60 mg/kg Fe and 5 × 109 CFU/kg B. subtilis showed the highest percentage of hatched eggs (P = 0.004) and mean corpuscular hemoglobin (P < 0.001) among the 6 groups. Supplementation of 40 and 60 mg/kg Fe significantly increased the apparent digestibility of calcium compared with that of 80 mg/kg Fe in the birds fed 5.0 × 109 CFU/kg B. subtilis (P = 0.004). Supplementation with 60 and 80 mg/kg Fe in the birds fed 5 × 109 CFU/kg B. subtilis significantly decreased serum urea nitrogen level compared with other 4 groups (P = 0.022). In conclusion, the combination of Fe and B. subtilis effectively improves reproductive performance, eggshell quality, nutrient digestibility, antioxidant status, and hematopoietic function of breeder geese. Dietary addition of 60 mg/kg Fe and 5.0 × 109 CFU/kg B. subtilis was an optimum supplementation dose.

Effects of manganese and Bacillus subtilis on the reproductive performance, egg quality, antioxidant capacity, and gut microbiota of breeding geese during laying period.

This experiment was conducted to investigate the effects of manganese (Mn) and Bacillus subtilis (BS) on the production performance, egg quality, antioxidant capacity, and gut microbiota of breeding geese during laying period. A total of 120 forty-six-week-old breeding geese (Wulong) were randomly assigned to 1 of 6 treatment diets formulated to supply 10, 20, and 30 mg/kg Mn with 5 × 109 CFU/kg or 2.5 × 109 CFU/kg BS for a 10-wk trial. Results showed that dietary supplementation with 20 and 30 mg/kg Mn could decrease the daily feed intake (DFI) of geese. Moreover, 30 mg/kg Mn significantly increased the laying rate. Besides, although Mn addition had no obvious effect on egg quality, 5 × 109 CFU/kg BS was found to elevate the hatching egg hatching rate and eggshell thickness. For the serum hormones, 30 mg/kg Mn promoted estradiol secretion, while 5 × 109 CFU/kg BS increased the level of follicle-stimulating hormone. Furthermore, 20 and 30 mg/kg Mn and 5 × 109 CFU/kg BS significantly enhanced the total antioxidant capacity by increasing the activity of total superoxide dismutases or decreasing the content of malondialdehyde. Dietary supplementation with 5 × 109 CFU/kg BS also increased the intestinal villus height and upregulated the abundance of Fusobacteria, Fusobacteriaceae, Fusobacterium, and Faecalibacterium in cecal content. In addition, 20 and 30 mg/kg Mn elevated the levels of Bacteroidetes, Bacteroidaceae, Bacteroides, and Ruminococcaceae but decreased Streptococcaceae. Importantly, an interaction effect was observed between Mn and BS on the DFI, egg mass, average egg size, and the abundance of Bacteroides as well as Faecalibacterium. In conclusion, dietary inclusion of Mn and BS could improve the production performance, egg quality, antioxidant capacity, intestinal structure, as well as gut microbiota. Supplementation of 30 mg/kg Mn and 5.0 × 109 CFU/kg BS provided the optimal effect.

Transcriptome Analysis Reveals the Effects of Chinese Chive (Allium tuberosum R.) Extract on Fusarium oxysporum f. sp. radicis-lycopersici Spore Germination.

Fusarium oxysporum f. sp. radicis-lycopersici (Forl) causes Fusarium crown and root rot of tomato, leading to severe yield losses. Chinese chive and the Chinese chive extract reportedly have antifungal effects. In this study, Chinese chive extract treatments inhibited Forl spore germination, with an EC50 of 0.40 g ml-1 in vitro. Furthermore, the mechanism underlying the fungicidal effects of the Chinese chive extract was analyzed by RNA sequencing. A total of 1252 differentially expressed genes (DEGs) were detected, of which 396 were upregulated and 856 were downregulated. The DEGs were related to starch and sucrose metabolism, amino sugar and nucleotide sugar metabolism, galactose metabolism, fatty acid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, peroxisomes, ribosome biogenesis in eukaryotes, mismatch repair, and the phosphatidylinositol signaling system, implying these pathways contribute to the fungicidal activity of the Chinese chive extract. The qRT-PCR results verified the accuracy of the RNA sequencing data. Thus, the Chinese chive extract can inhibit Forl spore germination by affecting spore nutrient metabolism.

Antibiotic angucycline derivatives from the deepsea-derived Streptomyces lusitanus.

A new (1, grincamycin L) and two known (2 and 3) angucycline derivatives were obtained from the fermentation of deepsea-derived Streptomyces lusitanus OUCT16-27 strain. The structures of 1-3 were elucidated based on the LC-MS analysis together with 1D and 2D NMR data assignment. In the antibacterial assay, 1 and 2 exhibited moderate growth inhibitions against multi-drug resistant (MDR) strains of E. faecium, E. faecalis and S. aureus with the minimum inhibitory concentrations (MICs) of 3.12-6.25 µg/mL.

Comparative Chloroplast Genome Analyses of Species in Gentiana section Cruciata (Gentianaceae) and the Development of Authentication Markers.

Gentiana section Cruciata is widely distributed across Eurasia at high altitudes, and some species in this section are used as traditional Chinese medicine. Accurate identification of these species is important for their utilization and conservation. Due to similar morphological and chemical characteristics, correct discrimination of these species still remains problematic. Here, we sequenced three complete chloroplast (cp) genomes (G. dahurica, G. siphonantha and G. officinalis). We further compared them with the previously published plastomes from sect. Cruciata and developed highly polymorphic molecular markers for species authentication. The eight cp genomes shared the highly conserved structure and contained 112 unique genes arranged in the same order, including 78 protein-coding genes, 30 tRNAs, and 4 rRNAs. We analyzed the repeats and nucleotide substitutions in these plastomes and detected several highly variable regions. We found that four genes (accD, clpP, matK and ycf1) were subject to positive selection, and sixteen InDel-variable loci with high discriminatory powers were selected as candidate barcodes. Our phylogenetic analyses based on plastomes further confirmed the monophyly of sect. Cruciata and primarily elucidated the phylogeny of Gentianales. This study indicated that cp genomes can provide more integrated information for better elucidating the phylogenetic pattern and improving discriminatory power during species authentication.