Pharmacokinetics of Enrofloxacin in Plasma, Urine, and Feces of Donkey (Equus asinus) after a Single Intragastric Administration.

Enrofloxacin is a broad-spectrum antimicrobial agent, but the study of its pharmacokinetics/pharmacodynamics (PKs/PDs) in donkeys is rarely reported. The present study aimed to investigate the pharmacokinetics of enrofloxacin administered intragastrically, and to study the pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in plasma, urine, and feces, and the PK/PD parameters were investigated to provide a rationale for enrofloxacin treatment in donkeys. A total of five healthy donkeys were selected for intragastric administration of 7.5 mg·kg-1 BW of enrofloxacin by gavage, and blood, urine, and fecal samples were collected. The results showed that the elimination half-life of plasma enrofloxacin was 11.40 ± 6.40 h, Tmax was 0.55 ± 0.12 h, Cmax was 2.46 ± 0.14 mg·L-1, AUC0-∞ was 10.30 ± 3.37 mg·L-1·h, and mean residence time (MRT) was 7.88 ± 1.26 h. The Tmax of plasma ciprofloxacin was 0.52 ± 0.08 h, Cmax was 0.14 ± 0.03 mg·L-1, and AUC0-∞ was 0.24 ± 0.16 mg·L-1·h. Urinary Cmax was 38.18 ± 8.56 mg·L-1 for enrofloxacin and 15.94 ± 4.15 mg·L-1 for ciprofloxacin. The total enrofloxacin and ciprofloxacin recovered amount in urine was 7.09 ± 2.55% of the dose for 144 h after dosing. The total enrofloxacin and ciprofloxacin recovered amount in feces was 25.73 ± 10.34% of the dose for 144 h after dosing. PK/PD parameters were also examined in this study, based on published MICs. In conclusion, 7.5 mg/kg BW of enrofloxacin administered intragastrically to donkeys was rapidly absorbed, widely distributed, and slowly eliminated in their bodies, and was predicted to be effective against bacteria with MICs < 0.25 mg·L-1.

Pharmacokinetics of tilmicosin in plasma, urine and feces after a single intragastric administration in donkey (Equus asinus).

Tilmicosin, a macrolide antibiotic, has the potential to treat bacterial infections in donkeys. However, the pharmacokinetics of tilmicosin in donkeys have not been reported. The aim of this study was to investigate the pharmacokinetics of tilmicosin in donkey plasma, urine, and feces after a single intragastric administration to determine the suitability of tilmicosin for donkeys. A total of 5 healthy male donkeys with similar body weights were selected. The donkeys were administered a single dose of 10 mg · kg-1 body weight (BW) tilmicosin by gavage. The concentrations of tilmicosin in plasma, urine, and feces were determined. The results showed that after a single intragastric administration of 10 mg · kg-1 body weight, tilmicosin in donkey plasma reached a maximum concentration of 11.23 ± 5.37 mg · L-1 at 0.80 ± 0.10 h, with a half-life of 14.49 ± 7.13 h, a mean residence time of 28.05 ± 3.05 h, a Cl/F of 0.48 ± 0.18 L · kg-1 · h-1, and a Vd/F of 9.28 ± 2.63 Lkg-1. The percentage of tilmicosin excreted through the urine of donkeys is 2.47%, and the percentage excreted through the feces is 66.43%. Our study provides data to inform the use of tilmicosin in donkeys.

The Toxicokinetics, Excretion Patterns, and Milk Transmission of Ochratoxin A in Lactating Sows.

Ochratoxin A (OTA), a mycotoxin commonly found in feedstuffs, is known for its detrimental effects on the kidneys and liver, posing significant health risks to animals and humans. This study investigated the toxicokinetics, excretion patterns, and milk transmission of Ochratoxin A (OTA) in lactating sows. The sows were administered a single oral dose of 500 µg/kg BW (body weight), followed by the systematic sampling of plasma, feces, urine, and milk. Plasma samples were collected at 0, 5, 15, and 30 min, and 1, 2, 3, 6, 9, 12, 24, 48, 72, 88, 96, and 120 h post administration. Feces samples were collected at 6 h intervals for the first 12 h, then at 12 h intervals until 120 h, while urine samples were collected at 6 h intervals up to 120 h. Milk samples were collected at 0, 6, 12, 24, 36, 48, 72, 96, and 120 h. The concentration of OTA and its primary metabolite OTα were quantitatively analyzed using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The results revealed that the peak plasma concentrations of OTA (920.25 ± 88.46 µg/L) were observed at 9 h following administration. The terminal elimination half-life was recorded at 78.47 ± 7.68 h, with a volume of distribution of 0.16 ± 0.003 L/kg. Moreover, this study documented the excretion of OTA and OTα across a span of 120 h, revealing that feces and urine accounted for 18.70 ± 0.04% and 8.40 ± 0.002% of the total intake amounts, respectively (calculated based on substance amounts). Furthermore, this experiment detected OTA residues in the milk of lactating sows, with the milk-to-plasma (M/P) ratio initially increasing from 0.06 to 0.46 within the first 24 h following OTA ingestion. These findings offer an exhaustive temporal analysis of OTA's toxicokinetics in lactating sows, emphasizing its pervasive distribution and elimination through various bodily excreta.

Agaro-oligosaccharides mitigate deoxynivalenol-induced intestinal inflammation by regulating gut microbiota and enhancing intestinal barrier function in mice.

Agarose-derived agaro-oligosaccharides (AgaroS) have been extensively studied in terms of structures and bioactivities; they reportedly possess antioxidant and anti-inflammatory activities that maintain intestinal homeostasis and host health. However, the protective effects of AgaroS on deoxynivalenol (DON)-induced intestinal dysfunction remain unclear. We investigated the effects of AgaroS on DON-induced intestinal dysfunction in mice and explored the underlying protective mechanisms. In total, 32 mice were randomly allocated to four treatments (n = 8 each) for 28 days. From day 1 to day 21, the control (CON) and DON groups received oral phosphate-buffered saline (200 µL per day); the AgaroS and AgaroS + DON groups received 200 mg AgaroS per kg body weight once daily by orogastric gavage. Experimental intestinal injury was induced by adding DON (4.8 mg per kg body weight) via gavage from day 21 to day 28. Phosphate-buffered saline was administered once daily by gavage in the CON and AgaroS groups. Herein, AgaroS supplementation led to a higher final body weight and smaller body weight loss and a lower concentration of plasma inflammatory cytokines, compared with the DON group. The DON group showed a significantly reduced ileal villus height and villus height/crypt depth, compared with the CON and AgaroS + DON groups. However, AgaroS supplementation improved DON-induced intestinal injury in mice. Compared with the DON group, ileal and colonic protein expression levels of claudin, occludin, Ki67, and mucin2 were significantly higher in the AgaroS supplementation group. Colonic levels of the anti-inflammatory cytokine IL-1ß tended to be higher in the DON group than in the AgaroS + DON group. AgaroS altered the gut microbiota composition, accompanied by increased production of short-chain fatty acids in mice. In conclusion, our findings highlight a promising anti-mycotoxin approach whereby AgaroS alleviate DON-induced intestinal inflammation by modulating intestinal barrier functional integrity and gut microbiota in mice.

Effects of dietary methionine supplementation on the growth performance, immune responses, antioxidant capacity, and subsequent development of layer chicks.

Deficiencies or excesses of dietary amino acids, and especially of methionine (Met), in laying hens can lead to abnormal protein anabolism and oxidative stress, which affect methylation and cause cellular dysfunction. This study investigated the effects of dietary methionine (Met) levels on growth performance, metabolism, immune response, antioxidant capacity, and the subsequent development of laying hens. A total of 384 healthy 1-day-old Hyline Grey chicks of similar body weight were randomly allocated to be fed diets containing 0.31%, 0.38%, 0.43% (control group), or 0.54% Met for 6 wk, with 6 replicates of 16 chicks in each. The growth performance of the chicks was then followed until 20 wk old. The results showed dietary supplementation with 0.43% or 0.54% Met significantly increased their mean daily body weight gain, final weight, and Met intake. However, the feed:gain (F/G) decreased linearly with increasing Met supplementation, from 0.31 to 0.54% Met. Met supplementation increased the serum albumin, IgM, and total glutathione concentrations of 14-day-old chicks. In contrast, the serum alkaline phosphatase activity and hydroxyl radical concentration tended to decrease with increasing Met supplementation. In addition, the highest serum concentrations of IL-10, T-SOD, and GSH-PX were in the 0.54% Met-fed group. At 42 d of age, the serum ALB, IL-10, T-SOD, GSH-PX, T-AOC, and T-GSH were correlated with dietary Met levels. Finally, Met supplementation reduced the serum concentrations of ALP, IL-1ß, IgA, IgG, hydrogen peroxide, and hydroxyl radicals. Thus, the inclusion of 0.43% or 0.54% Met in the diet helps chicks achieve superior performance during the brooding period and subsequently. In conclusion, Met doses of 0.43 to 0.54% could enhance the growth performance, protein utilization efficiency, antioxidant capacity, and immune responses of layer chicks, and to promote more desirable subsequent development during the brooding period.

Using low-protein diet in egg production for win-win of productivity and environmental benefits should be prudent: Evidence from pilot test.

A shortage of feed protein resources restricts poultry productivity. Key strategies to alleviate this problem include improvements to the structure of the gut microbiota by the appropriate intake of high-quality protein, improvements to the comprehensive protein utilization rate, and reducing the consumption of protein raw materials. In addition, damage to the environment caused by nitrogen emissions needs to be reduced. The aim of the study was to evaluate the effects of dietary protein levels on laying performance, host metabolism, ovarian health, nitrogen emissions, and the gut microbial structure and function of laying hens. In total, 360 hens at the age of 38 weeks were randomly allotted four treatments. Each of the groups consisted of nine replicates, with 10 birds per replicate, used for 12 weeks of study. Dietary protein levels of the four groups were 13.85 %, 14.41 %, 15.63 %, and 16.30 %. Results revealed that, compared with the 13.85 % crude protein (CP) group, the 15.63 % CP group experienced significantly enhanced final body weight, average daily gain, egg production, and egg mass. Compared with the 16.30 % CP group, the other groups' serum concentrations of immunoglobulin G (IgG) and immunoglobulin M (IgM) were significantly reduced. Compared with the 16.30 % CP group, the 13.85 % and 15.63 % groups had increased CP utilization rates but reduced nitrogen emission rate, and daily per egg and per kilogram egg nitrogen emissions rose with increased dietary protein levels. Compared to the 13.85 % and 14.41 % CP groups, the 16.30 % CP group exhibited a significant increase in the expression of genes related to amino acids and carbohydrate metabolic pathways. According to the linear discriminant analysis effect size diagram, the predominant bacteria in the 15.63 % CP group (e.g., Subdoligranulum, and Ruminococcaceae_UCG-013) were significantly related to CP utilization. The results of this study emphasize that production performance is significantly reduced when protein levels are too low, whereas too high protein levels lead to gut microbiota imbalance and a reduction in the utilization efficiency of nutrients. Therefore, on the premise of ensuring the health of hens, the structure of the gut microbiota can be improved by appropriately reducing protein levels, which helps to balance the relationships among host health, productivity, resources, and the environment.

Toxicokinetics of Deoxynivalenol in Dezhou Male Donkeys after Oral Administration.

Deoxynivalenol (DON) is detected in different types of foods and feeds, inducing toxicity in humans and animals. After entering the organism, DON first appears in the plasma; then, it is rapidly absorbed and distributed in various organs and tends to accumulate in the body to exert its toxic effects. This study was performed to investigate the toxicokinetics of DON on Dezhou male donkeys after a single oral dose of 500 µg/kg·BW (body weight). The plasma of donkeys was collected at 0, 5, 10, 15, 20, 30, 45 min, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 6, 9, 12, 24, 48, 72, 96 and 120 h after administration, and the feces and urine were collected at 0 h and at 6 h intervals up to 24 h, followed by 4 h intervals up to 120 h. The concentrations of DON in plasma, urine and feces were determined by HPLC. The peak concentration of DON in plasma was 174.30 µg/L, which occurred at 1.07 h after oral gavage. The recovery of unchanged DON in urine and feces amounted to 19.98% and 6.74%, respectively. Overall, DON was rapidly absorbed and slowly eliminated in donkeys within 120 h following a single oral dose, which can lead to DON accumulation in the body if ingested for a long time.

Supervised learning and model analysis with compositional data.

Supervised learning, such as regression and classification, is an essential tool for analyzing modern high-throughput sequencing data, for example in microbiome research. However, due to the compositionality and sparsity, existing techniques are often inadequate. Either they rely on extensions of the linear log-contrast model (which adjust for compositionality but cannot account for complex signals or sparsity) or they are based on black-box machine learning methods (which may capture useful signals, but lack interpretability due to the compositionality). We propose KernelBiome, a kernel-based nonparametric regression and classification framework for compositional data. It is tailored to sparse compositional data and is able to incorporate prior knowledge, such as phylogenetic structure. KernelBiome captures complex signals, including in the zero-structure, while automatically adapting model complexity. We demonstrate on par or improved predictive performance compared with state-of-the-art machine learning methods on 33 publicly available microbiome datasets. Additionally, our framework provides two key advantages: (i) We propose two novel quantities to interpret contributions of individual components and prove that they consistently estimate average perturbation effects of the conditional mean, extending the interpretability of linear log-contrast coefficients to nonparametric models. (ii) We show that the connection between kernels and distances aids interpretability and provides a data-driven embedding that can augment further analysis. KernelBiome is available as an open-source Python package on PyPI and at https://github.com/shimenghuang/KernelBiome.

Synergistic catalysis induced by a multi-component system constructed by DBD plasma combined with α-Fe2O3/FeVO4/HCP and peroxymonosulfate for gatifloxacin removal.

The dielectric barrier discharge (DBD) multi-component system containing plasma, α-Fe2O3/FeVO4, and peroxymonosulfate (PMS) with high catalytic activity was successfully constructed. Thereinto, α-Fe2O3/FeVO4 was loaded on the honeycomb ceramic plate (HCP) surface (α-Fe2O3/FeVO4/HCP) and placed under the water surface below the discharge area. The catalytic activity was evaluated by the removal rate of gatifloxacin (GAT), and the DBD+α-Fe2O3/FeVO4+PMS system exhibited the optimal catalytic activity. The enhanced catalytic activity can be attributed to the fact that the occurrence of synergistic catalysis that simultaneously includes plasma oxidation, photocatalysis, PMS oxidation, O3 catalysis, and Fenton reaction. The effect of various initial degradation parameters including input power, PMS dosage, pH, etc. On GAT removal was investigated. DBD+α-Fe2O3/FeVO4+PMS system has a significant increase in the concentration of H2O2 and O3, and the role played in the multi-component system was analyzed. The identification and analysis of organic matters during GAT degradation were visualized with the help of 3D EEMs. HPLC-MS and theoretical calculations identified the major intermediates and further deduced the possible GAT degradation pathways. Additionally, the acute toxicity of the major intermediates was predicted by the QSAR model. Finally, the possible mechanisms of synergistic catalysis to enhance catalytic activity were discussed based on the characteristics of several advanced oxidation processes (AOPs) and the results of experimental and characterization. This work provides a feasible technical route and theoretical basis for wastewater treatment by plasma combined with other AOPs.

Toxicokinetics of a Single Oral Dose of OTA on Dezhou Male Donkeys.

Ochratoxin (OTA) is widely present in a wide range of foods and feeds, causing adverse effects on animals and humans. This study aims to explore the toxicokinetics of OTA-contaminated materials on the Dezhou male donkey. Donkeys received a single orally dose of 2500 µg OTA/kg BW, obtained from Aspergillus ochraceus culture material. The concentrations of OTA in plasma collected at 0, 5, 10, 15, 20, 30, 45 min, and at 1, 1.5, 2, 3, 6, 9, 12, 24, 48, 72, 96 and 120 h were detected by HPLC. OTA eliminated in urine and feces were quantified at 6-h intervals up to 24 h and then at 4-h intervals up to 120 h. The results suggested that the maximum concentration of OTA in plasma was observed at 12 h after administration, with a mean value of 10.34 µg/mL. The total excretion in both urine and feces was about 10% of the intake until 120 h.

Pharmacokinetics of florfenicol and its metabolite florfenicol amine in the plasma, urine, and feces of fattening male donkeys following single oral administration.

Florfenicol (FF) is a commonly used antibacterial agent in animals. We investigated the pharmacokinetics of FF and its metabolite florfenicol amine (FFA) in donkeys. Donkeys were administered FF (30 mg/kg bodyweight, p.o.). Pharmacokinetic parameters were calculated using a non-compartmental model. The FF (FFA) pharmacokinetics parameters were characterized by along elimination half-life (t1/2 kz) of 5.92 h (15.95 h), plasma peak concentration (Cmax) of 0.13 µg/mL (0.08 µg/mL), and the time taken to reach Cmax (Tmax) of 0.68 h (0.72 h). The area under plasma concentration-time curve and mean residence time of FF (FFA) in plasma were 1.31 µg·mL-1·h (0.47 µg·mL-1·h) and 10.37 h (18.40 h), respectively. The t1/2 kz of FF and FFA in urine was 21.93 and 40.26 h, and the maximum excretion rate was 10.56 and 4.03 µg/h reached at 25.60 and 32.20 h, respectively. The respective values in feces were 0.02 and 0.01 µg·h-1 reached at 33.40 h. The amount of FF and FFA recovered in feces was 0.52 and 0.22 µg, respectively. In conclusion, FF (FFA) is rapidly absorbed and slowly eliminated after a single oral administration to donkeys. Compared to FF, FFA was more slowly eliminated. FF (FFA) is mostly excreted through urine.

Small extracellular vesicles from Ptpn1-deficient macrophages alleviate intestinal inflammation by reprogramming macrophage polarization via lactadherin enrichment.

Tyrosine-protein phosphatase non-receptor type 1 (Ptpn1) is known to be involved in macrophage polarization. However, whether and how Ptpn1 regulates macrophage phenotype to affect intestinal epithelial barrier function remains largely unexplored. Herein, we investigated the impact of Ptpn1 and macrophage-derived small extracellular vesicles (sEVs) on macrophage-intestinal epithelial cell (IEC) interactions in the context of intestinal inflammation. We found that Ptpn1 knockdown shifts macrophages toward the anti-inflammatory M2 phenotype, thereby promoting intestinal barrier integrity and suppressing inflammatory response in the macrophage-IEC co-culture model. We further revealed that conditioned medium or sEVs isolated from Ptp1b knockdown macrophages are the primary factor driving the beneficial outcomes. Consistently, administration of the sEVs from Ptpn1-knockdown macrophages reduced disease severity and ameliorated intestinal inflammation in LPS-challenged mice. Furthermore, depletion of macrophages in mice abrogated the protective effect of Ptpn1-knockdown macrophage sEVs against Salmonella Typhimurium infection. Importantly, we found lactadherin to be highly enriched in the sEVs of Ptpn1-knockdown macrophages. Administration of recombinant lactadherin alleviated intestinal inflammation and barrier dysfunction by inducing macrophage M2 polarization. Interestingly, sEVs lactadherin was also internalized by macrophages and IECs, leading to macrophage M2 polarization and enhanced intestinal barrier integrity. Mechanistically, the anti-inflammatory and barrier-enhancing effect of lactadherin was achieved by reducing TNF-α and NF-κB activation. Thus, we demonstrated that sEVs from Ptpn1-knockdown macrophages mediate the communication between IECs and macrophages through enrichment of lactadherin. The outcome could potentially lead to the development of novel therapies for intestinal inflammatory disorders.

Dietary supplementation of porcine bile acids improves laying performance, serum lipid metabolism and cecal microbiota in late-phase laying hens.

Due to the exceptional laying performance of hens, the demand on lipid metabolism and oxidation in vivo is vigorous, resulting in excessive lipid accumulation in late-phase hens, which lowers the production performance. Bile acids regulate lipid metabolism and gut microbiota in humans and animals. However, the effect of porcine bile acids on lipid metabolism and cecal microbiota in laying hens in the late phase is still unclear. A total of 360 healthy 45-week-old laying hens were chosen for a 24-week feeding trial, where 0, 30, 60 and 90 mg/kg porcine bile acids were added to a basal diet, respectively. The results showed that dietary supplementation of 60 mg/kg bile acids increased egg production and feed conversion (P < 0.05). Also, 60 and 90 mg/kg porcine bile acids reduced abdominal fat percentage and body weight (P < 0.05). The levels of serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol of hens decreased (P < 0.05) in bile acids supplement groups. As for cecal microbiota, bile acids supplementation did not affect the alpha diversity of cecal microbiota at the genus level. Moreover, dietary supplementation of 90 mg/kg bile acids resulted in an increase in the abundance of beneficial bacteria in the cecum, such as Lactobacillus, Bifidobacterium and Turicibacter. The changes in the cecal microbiota caused by bile acids supplementation correlated with serum lipid indexes. According to KEGG pathway analysis, dietary supplementation of 60 and 90 mg/kg bile acids promoted structural transformation of the cecal microbiota to down-regulate steroid biosynthesis, up-regulate fatty acid degradation and up-regulate unsaturated fatty acid biosynthesis. Meanwhile, bile acids bio-isomerization function of cecal microbiota was enhanced in 60 and 90 mg/kg bile acids treatment, and the short-chain fatty acid metabolism was also affected. In conclusion, the present study revealed dietary supplementation of porcine bile acids enriched probiotics in the gut and improved serum lipid metabolism of laying hens. These findings demonstrate that porcine bile acids can be a potential gut beneficial promoter for late-phase laying hens.

Porcine bile acids promote the utilization of fat and vitamin A under low-fat diets.

Fat-soluble vitamin malabsorption may occur due to low dietary fat content, even in the presence of an adequate supply of fat-soluble vitamins. Bile acids (BAs) have been confirmed as emulsifiers to promote fat absorption in high-fat diets. However, there are no direct evidence of exogenous BAs promoting the utilization of fat-soluble vitamins associated with fat absorption in vitro and in vivo. Therefore, we chose laying hens as model animals, as their diet usually does not contain much fat, to expand the study of BAs. BAs were investigated in vitro for emulsification, simulated intestinal digestion, and release rate of fat-soluble vitamins. Subsequently, a total of 450 healthy 45-week-old Hy-Line Gray laying hens were chosen for an 84-day feeding trial. They were divided into five treatments, feeding diets supplemented with 0, 30, 60, 90, and 120 mg/kg BAs, respectively. No extra fat was added to the basic diet (crude fat was 3.23%). In vitro, BAs effectively emulsified the water-oil interface. Moreover, BAs promoted the hydrolysis of fat by lipase to release more fatty acids. Although BAs increased the release rates of vitamins A, D, and E from vegetable oils, BAs improved for the digestion of vitamin A more effectively. Dietary supplementation of 60 mg/kg BAs in laying hens markedly improved the laying performance. The total number of follicles in ovaries increased in 30 and 60 mg/kg BAs groups. Both the crude fat and total energy utilization rates of BAs groups were improved. Lipase and lipoprotein lipase activities were enhanced in the small intestine in 60, 90, and 120 mg/kg BAs groups. Furthermore, we observed an increase in vitamin A content in the liver and serum of laying hens in the 60, 90, and 120 mg/kg BAs groups. The serum IgA content in the 90 and 120 mg/kg BAs groups was significantly improved. A decrease in serum malondialdehyde levels and an increase in glutathione peroxidase activity were also observed in BAs groups. The present study concluded that BAs promoted the absorption of vitamin A by promoting the absorption of fat even under low-fat diets, thereupon improving the reproduction and health of model animals.

Dietary selenium sources alleviate immune challenge induced by Salmonella Enteritidis potentially through improving the host immune response and gut microbiota in laying hens.

The aim of this study was to evaluate the effects of different selenium (Se) sources on the immune responses and gut microbiota of laying hens challenged with Salmonella enteritidis (S. Enteritidis). A total of 240 45-week-old layers were randomly divided into eight groups with six replicates per group according to a 4 × 2 factorial design, including a blank diet without Se supplementation (CON group) and three diets with 0.3 mg/kg Se supplementation from sodium selenite (IS group), yeast Se (YS group), and selenium-enriched yeast culture (SYC group), respectively. After 8 weeks of feeding, half of them were orally challenged with 1.0 ml suspension of 109 colony-forming units per milliliter of S. Enteritidis daily for 3 days. The serum was collected on days 3, 7, and 14, and the cecum content was collected on day 14 after challenge. There was no significant difference in laying performance among the eight groups before challenge. The S. Enteritidis challenge significantly decreased the laying performance, egg quality, GSH-Px, IgG, and IgM and increased the ratio of feed and egg, malondialdehyde (MDA), Salmonella-specific antibody (SA) titers, IL-6, IL-2, IL-1ß, and INF-γ. However, SYC increased the level of GSH-Px and IgG and decreased IL-6, while YS decreased the level of IL-2 and IL-1ß. What is more, Se supplementation decreased the SA titers to varying degrees and reduced the inflammatory cell infiltration in the lamina propria caused by S. Enteritidis infection. In addition, the S. Enteritidis challenge disrupted the intestinal flora balance by reducing the abundance of the genera Clostridium innocuum, Lachnospiraceae, and Bifidobacterium and increasing the genera Butyricimonas and Brachyspira, while Se supplementation increased the gut microbial alpha diversity whether challenged or not. Under the S. Enteritidis challenge condition, the alteration of microbial composition by the administration of different Se sources mainly manifested as IS increased the relative abundance of the genera Lachnospiraceae and Christensenellaceae, YS increased the relative abundance of the genera Megamonas and Sphingomonas, and SYC increased the genera Fusobacterium and Lactococcus. The alteration of gut microbial composition had a close relationship with antioxidant or immune response. To summarize, different Se sources can improve the egg quality of layers challenged by S. Enteritidis that involves elevating the immunity level and regulating the intestinal microbiota.

Combined Toxicity Evaluation of Ochratoxin A and Aflatoxin B1 on Kidney and Liver Injury, Immune Inflammation, and Gut Microbiota Alteration Through Pair-Feeding Pullet Model.

Ochratoxin A (OTA) and aflatoxin B1 (AFB1) are often co-contaminated, but their synergistic toxicity in poultry is limitedly described. Furthermore, the traditional ad libitum feeding model may fail to distinguish the specific impact of mycotoxins on the biomarkers and the indirect effect of mildew on the palatability of feed. A pair-feeding model was introduced to investigate the specific effect and the indirect effect of the combined toxicity of OTA and AFB1, which were independent and dependent on feed intake, respectively. A total of 180 one-day-old pullets were randomly divided into 3 groups with 6 replicates, and each replicate contained 10 chicks. The control group (Group A) and the pair-feeding group (Group B) received the basal diet without mycotoxin contamination. Group C was administrated with OTA- and AFB1-contaminated feed (101.41 µg/kg of OTA + 20.10 µg/kg of AFB1). The scale of feeding in Group B matched with the feed intake of Group C. The trial lasted 42 days. Compared with the control group, co-contamination of OTA and AFB1 in feed could adversely affect the growth performance (average daily feed intake (ADFI), body weight (BW), average daily weight gain (ADG), feed conversion ratio (FCR), and shank length (SL)), decrease the relative weight of the spleen (p < 0.01), and increase the relative weight of the kidney (p < 0.01). Moreover, the reduction of feed intake could also adversely affect the growth performance (BW, ADG, and SL), but not as severely as mycotoxins do. Apart from that, OTA and AFB1 also activated the antioxidative and inflammation reactions of chicks, increasing the level of catalase (CAT), reactive oxygen species (ROS), and interleukin-8 (IL-8) while decreasing the level of IL-10 (p < 0.01), which was weakly influenced by the feed intake reduction. In addition, OTA and AFB1 induced histopathological changes and apoptosis in the kidney and liver as well as stimulated the growth of pernicious bacteria to cause toxic effects. There were no histopathological changes and apoptosis in the kidney and liver of the pair-feeding group. The combined toxicity of OTA and AFB1 had more severe effects on pullets than merely reducing feed supply. However, the proper reduction of the feed intake could improve pullets' physical health by enriching the bacteria Lactobacillus, Phascolarctobacterium, Bacteroides, Parabacteroides, and Barnesiella.

Surgical revision for pancreatojejunostomy stricture: a case series of 14 patients.

BACKGROUND: Pancreatojejunostomy stricture (PJS) is a rare long-term complication of pancreaticojejunal anastomosis. This study aimed to investigate the role of surgery in the management of pancreatojejunostomy strictures. METHODS: The database of the Pancreas Center of Nanjing Medical University was retrospectively screened for patients who underwent a surgical revision for PJS between June 2012 and August 2019, and their clinical characteristics and management modalities were reviewed. RESULTS: Fourteen consecutive cases were retrieved, the median age at index operation was 41.1 years (19-71). The average time between the two operations was 70.6 months (8-270 months). Index procedures included pancreaticoduodenectomy (PD) (7/14, 50%), pylorus-preserving PD (4/14, 28.6%), Berger procedure (2/14, 14.3%), and middle pancreatectomy (1/14, 7.1%). The diameter of the main pancreatic duct was < 4 mm in all 14 cases, and nine underwent pancreaticojejunostomy (PJ) stenting during the index operation. The most frequent complaints were abdominal pain (6/14, 42.9%), recurrent acute pancreatitis (6/14, 42.9%), pancreatic fistula (1/14, 7.1%), and abdominal distention (1/14, 7.1%). The diagnosis of PJ stricture was confirmed by computed tomography or magnetic resonance imaging in all cases. All patients had a main duct diameter > 5 mm before surgical revision. All patients underwent wedge excision with interrupted one-layer suturing with absorbable sutures and without stent placement. In this series, only one patient required reoperation. Upon follow-up, 11 of 12 patients had complete resolution of the PJ stricture. CONCLUSION: PJS is a long-term complication of pancreatojejunostomy. Surgical revision of the anastomosis is a safe and effective treatment modality.

R- Is Superior to S-Form of α-Lipoic Acid in Anti-Inflammatory and Antioxidant Effects in Laying Hens.

The development of single enantiomers with high efficiency and low toxic activity has become a hot spot for the development and application of drugs and active additives. The aim of the present study was to investigate the effectiveness of the application of α-lipoic acid with a different optical rotation to alleviate the inflammation response and oxidative stress induced by oxidized fish oil in laying hens. Sixty-four 124-week-old Peking Red laying hens were randomly allocated to four groups with eight replicates of two birds each. The normal group was fed basal diets supplemented with 1% fresh fish oil (FO), and the oxidative stress model group was constructed with diets supplemented with 1% oxidized fish oil (OFO). The two treatment groups were the S-form of the α-lipoic acid model with 1% oxidized fish oil (OFO + S-LA) and the R-form of the α-lipoic acid model with 1% oxidized fish oil (OFO + R-LA) added at 100 mg/kg, respectively. Herein, these results were evaluated by the breeding performance, immunoglobulin, immune response, estrogen secretion, antioxidant factors of the serum and oviduct, and pathological observation of the uterus part of the oviduct. From the results, diets supplemented with oxidized fish oil can be relatively successful in constructing a model of inflammation and oxidative stress. The OFO group significantly increased the levels of the serum inflammatory factor (TNF-α, IL-1ß, IL-6, and IFN-γ) and the oxidative factor MDA and decreased the activity of the antioxidant enzyme (T-AOC, T-SOD, GSH-Px, GSH, and CAT) in the oviduct. The addition of both S-LA and R-LA significantly reduced the levels of serum inflammatory factors (TNF-α, IL-1ß, IL-6, and IFN-γ), increased the activity of antioxidant indexes (T-AOC, T-SOD, GSH-Px, GSH, and CAT), and decreased the MDA contents in the serum and oviduct. Meanwhile, the supplementation of S-LA and R-LA also mitigated the negative effects of the OFO on the immunoglobulins (IgA and IgM) and serum hormone levels (P and E2). In addition, it was worth noting that the R-LA was significantly more effective than the S-LA in some inflammatory (IL-1ß) and antioxidant indices (T-SOD, GSH, and CAT). Above all, both S-LA and R-LA can alleviate the inflammation and oxidative damage caused by oxidative stress in aged laying hens, and R-LA is more effective than S-LA. Thus, these findings will provide basic data for the potential development of α-lipoic acid as a chiral dietary additive for laying hens.

A Newly Isolated Alcaligenes faecalis ANSA176 with the Capability of Alleviating Immune Injury and Inflammation through Efficiently Degrading Ochratoxin A.

Ochratoxin A (OTA) is one of the most prevalent mycotoxins that threatens food and feed safety. Biodegradation of OTA has gained much attention. In this study, an Alcaligenes faecalis strain named ANSA176, with a strong OTA-detoxifying ability, was isolated from donkey intestinal chyme and characterized. The strain ANSA176 could degrade 97.43% of 1 mg/mL OTA into OTα within 12 h, at 37 °C. The optimal levels for bacterial growth were 22-37 °C and pH 6.0-9.0. The effects of ANSA176 on laying hens with an OTA-contaminated diet were further investigated. A total of 36 laying hens were assigned to three dietary treatments: control group, OTA (250 µg/kg) group, and OTA + ANSA176 (6.2 × 108 CFU/kg diet) group. The results showed that OTA decreased the average daily feed intake (ADFI) and egg weight (EW); meanwhile, it increased serum alanine aminopeptidase (AAP), leucine aminopeptidase (LAP), ß2-microglobulin (ß2-MG), immunoglobulin G (IgG), tumor necrosis factor-α (TNF-α), and glutathione reductase (GR). However, the ANSA176 supplementation inhibited or attenuated the OTA-induced damages. Taken together, OTA-degrading strain A. faecalis ANSA176 was able to alleviate the immune injury and inflammation induced by OTA.

Milk Fat Globule Membrane Attenuates Acute Colitis and Secondary Liver Injury by Improving the Mucus Barrier and Regulating the Gut Microbiota.

Objective: Inflammatory bowel disease (IBD) often occurs along with extraintestinal manifestations, including hepatic injury. Milk fat globule membrane (MFGM) is an active substance with a potential anti-inflammation activity. However, its alleviated effect and mechanisms in IBD as well as the IBD-induced secondary liver injury are still unclear. Methods: C57BL/6J mice were administered with a 21-day oral gavage of MFGM, followed by 7 days of drinking water with 4% dextran sulfate sodium (DSS). Disease activity index (DAI), histological features, and cytokines of the colon and liver were evaluated. Then, RNA-seq of the colon and liver was conducted. The gut microbiota was assessed by analyzing 16S rRNA gene sequences, and finally the integrity and the function of the mucus barrier were evaluated by Alcian blue staining, real-time quantitative PCR, and ELISA. Results: Prophylactic MFGM treatment was effective against colitis to include effects in body weight loss, DAI score, colonic length, intestinal pathology, and histological score. Additionally, prophylactic MFGM decreased the levels of interleukin (IL)-1ß, IL-6, and myeloperoxidase in colonic tissue, while it increased the IL-10 level. Moreover, the gene expressions of MUC2, MUC4, Reg3b, and Reg3g associated with the production of the molecular mediator of immune response, membrane invagination, and response to protozoan were strikingly upregulated when administered with MFGM. On the other hand, the beneficial effects of MFGM were related to the enriched abundance of genera such as Faccalibacumum and Roseburia in feces samples. Consistently, the administration of MFGM was also found to alleviate DSS-induced hepatic injury. Furthermore, the glutathione transferase activity pathway was enriched in the liver of MFGM-treated mice after DSS administration. Mechanistically, prophylactic MFGM enhanced the mucosal barrier by increasing the gene levels of Reg3b and Reg3g. Meanwhile, the alleviation of MFGM on liver injury was dependent on the reduced hepatic oxidative stress. Conclusions: MFGM attenuated colitis and hepatic injury by maintaining the mucosal barrier and bacterial community while inhibiting oxidative stress, which might be an effective therapy of hepatic injury secondary to IBD.