Fermented Corn-Soybean Meal Improved Growth Performance and Reduced Diarrhea Incidence by Modulating Intestinal Barrier Function and Gut Microbiota in Weaned Piglets.

This study aimed to investigate the effects of fermented corn-soybean meal mixed feed (FMF) on growth performance, intestinal barrier function, gut microbiota and short-chain fatty acids in weaned piglets. A total of 128 weaned piglets [Duroc×(Landrace×Yorkshire), male, 21-day-old] were randomly allocated to four groups. Piglets were fed a control diet (CON) or the control diet supplemented with 10%, 50% or 100% FMF (FMF-10, FMF-50 or FMF-100, respectively) for 14 d. The results showed that the FMF-100 group had higher average daily gain and average daily feed intake and lower diarrhea incidence than the CON group (p < 0.05). The FMF-50 and FMF-100 groups had greater villus height in the duodenum and jejunum, and the FMF-10 and FMF-100 groups had higher villus height-to-crypt depth ratio in the duodenum and jejunum than the CON group. Additionally, the FMF-100 group had higher protein expression of duodenal, jejunal and ileal ZO-1 and jejunal claudin-1; higher mRNA expression of duodenal and ileal TJP1 and jejunal CLDN1 and IL10; and lower jejunal IL1B mRNA expression (p < 0.05). The FMF-50 group showed higher jejunal ZO-1 and claudin-1 protein levels, higher mRNA expression levels of IL10 and TJP1 and lower levels of TNF in the jejunum; the FMF-10 group had higher mRNA expression levels of IL10 and lower levels of TNF in the jejunum than the CON group (p < 0.05). Furthermore, the FMF-10 and FMF-50 groups had higher colonic Lactobacillus abundance and butyrate levels; the FMF-100 group had higher abundance of colonic butyrate, Lactobacillus and Faecalibacterium than the CON group (p < 0.05). Collectively, our results suggest that FMF could improve intestinal mucosal barrier function, gut microbiota and their metabolites, thereby enhancing average daily gain and reducing diarrhea incidence in weaned piglets.

Maternal resveratrol improves the intestinal health and weight gain of suckling piglets during high summer temperatures: The involvement of exosome-derived microRNAs and immunoglobin in colostrum.

Previous studies have shown that maternal resveratrol improved growth performance and altered the microbial composition of suckling piglets under hot summer conditions. However, it remains unclear how maternal resveratrol improves growth performance of suckling piglets during high summer temperatures. A total of 20 sows (Landrace × Large White; three parity) were randomly assigned to 2 groups (with or without 300 mg/kg resveratrol) from d 75 of gestation to d 21 of lactation during high ambient temperatures (from 27 to 30 °C). The results showed that maternal resveratrol supplementation increased total daily weight gain of piglets under hot summer conditions, which is consistent with previous studies. Furthermore, we found that maternal resveratrol improved the intestinal morphology and intestinal epithelial proliferation in suckling piglets. Dietary resveratrol supplementation affected the characteristics of exosome-derived microRNAs (miRNAs) in sow colostrum, as well as the genes targeted by differentially produced miRNAs. MiRNAs are concentrated in the tight junction pathway. As a result, the expression of intestinal tight junction proteins was increased in suckling piglets (P < 0.05). Notably, maternal resveratrol increased the intestinal secretory immunoglobulin A (sIgA) levels of suckling piglets via colostrum immunoglobin (P < 0.05), which could increase the abundance of beneficial microbiota to further increase the concentration of short chain fatty acids (SCFA) in suckling piglets' intestine (P < 0.05). Finally, our correlation analysis further demonstrated the positive associations between significantly differential intestinal microbiota, intestinal sIgA production and SCFA concentrations, as well as the positive relation between total daily weight gain and intestinal health of suckling piglets. Taken together, our findings suggested that maternal resveratrol could promote intestinal health to improve piglet growth during high summer temperatures, which might be associated with the immunoglobin and exosome-derived miRNAs in sows' colostrum.

Effect of mixed meal replacement of soybean meal on growth performance, nutrient apparent digestibility, and gut microbiota of finishing pigs.

Introduction: This study was carried out to investigate the effects of mixed meal (rapeseed meal, cotton meal, and sunflower meal) replacement soybean meal on growth performance, nutrient apparent digestibility, serum inflammatory factors and immunoglobulins, serum biochemical parameters, intestinal permeability, short-chain fatty acid content, and gut microbiota of finishing pigs. Methods: A total of 54 pigs with an average initial weight of 97.60 ± 0.30 kg were selected and randomly divided into 3 groups according to their initial weight, with 6 replicates in each group and 3 pigs in each replicate. The trial period was 26 days. The groups were as follows: control group (CON), fed corn-soybean meal type basal diet; Corn-soybean-mixed meal group (CSM), fed corn-soybean meal-mixed meal diet with a ratio of rapeseed meal, cotton meal, and sunflower meal of 1:1:1 to replace 9.06% soybean meal in the basal diet; Corn-mixed meal group (CMM), fed a corn-mixed meal diet with a ratio of Rapeseed meal, Cotton meal and Sunflower meal of 1:1:1 to replace soybean meal in the basal diet completely. The crude protein level of the three diets was maintained at 12.5%. Results: Our findings revealed no significant impact of replacing soybean meal with the mixed meal (rapeseed meal, cotton meal, and sunflower meal) on the ADG (Average daily gain), ADFI (Average daily feed intake), and F/G (Feed gain ratio) (P > 0.05), or crude protein, crude fat, and gross energy (P > 0.05) in the diet of finishing pigs. Compared with the CON group, the serum interleukin 6 (IL-6) and interleukin 10 (IL-10) concentrations were significantly decreased in the CMM group (P < 0.05). However, there is no significant effect of the mixed meal (rapeseed meal, cotton meal, and sunflower meal) replacing soybean meal in the diet on the serum interleukin 1ß (IL-1ß), interleukin 8 (IL-8), tumor necrosis factor-alpha (TNF-α), immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) concentrations (P > 0.05). Concordantly, there is no significant effect of mixed meal (rapeseed meal, cotton meal, and sunflower meal) replacing soybean meal in the diet on the serum antioxidant capacity, such as total antioxidant capacity (T-AOC), catalase (CAT), and malondialdehyde (MDA) levels of finishing pigs. Moreover, compared with the CON group, serum low-density lipoprotein (LDL-C) levels were significantly lower in the CSM group (P < 0.05) and their total bilirubin (TBIL) levels were significantly lower in the CMM group (P < 0.05). There is not a significant effect on serum D-lactate and diamine oxidase (DAO) concentrations (P > 0.05). The next section of the survey showed that the replacement of soybean meal with a mixed meal (rapeseed meal, cotton meal, and sunflower meal) in the diet did not significantly influence the acetic acid, propionic acid, butyric acid, valeric acid, isobutyric acid, and isovaleric acid in the colon contents (P > 0.05). Furthermore, compared with the CON group, the CMM group diet significantly increased the abundance of Actinobacteria at the phylum level (P < 0.05), U_Actinobacteria at the class level (P < 0.05), and U_Bacteria at the class level (P < 0.05). The result also showed that the CMM group significantly reduced the abundance of Oscillospirales at the order level (P < 0.05) and Streptococcaceae at the family level (P < 0.05) compared with the CON group. The Spearman correlation analysis depicted a statistically significant positive correlation identified at the class level between the relative abundance of U_Bacteria and the serum T. BILI concentrations (P < 0.05). Moreover, a significant negative correlation was detected at the order level between the relative abundance of Oscillospirales and the levels of acetic and propionic acids in the colonic contents (P < 0.05). Additionally, there was a significant positive correlation between the serum concentrations of IL-6 and IL-10 and the relative abundance of the family Streptococcaceae (P < 0.05). Discussion: This study demonstrated that the mixed meal (rapeseed meal, cotton meal, and sunflower meal) as a substitute for soybean meal in the diet had no significant negative effects on the growth performance, nutrient apparent digestibility, serum immunoglobulins, serum antioxidant capacity, intestinal permeability, short-chain fatty acid content, and diversity of gut microbiota of finishing pigs. These results can help develop further mixed meals (rapeseed meal, cotton meal, and sunflower meal) as a functional alternative feed ingredient for soybean meals in pig diets.

Accurate models and nutritional strategies for specific oxidative stress factors: Does the dose matter in swine production?

Oxidative stress has been associated with a number of physiological problems in swine, including reduced production efficiency. Recently, although there has been increased research into regulatory mechanisms and antioxidant strategies in relation to oxidative stress-induced pig production, it remains so far largely unsuccessful to develop accurate models and nutritional strategies for specific oxidative stress factors. Here, we discuss the dose and dose intensity of the causes of oxidative stress involving physiological, environmental and dietary factors, recent research models and the antioxidant strategies to provide theoretical guidance for future oxidative stress research in swine.

The Prevalence and Characteristics of Circulating IgA Anti-Glomerular Basement Membrane Autoantibodies in Anti-Glomerular Basement Membrane Disease.

Introduction: In some cases, immunoglobulin (IgA)-mediated antiglomerular basement membrane (anti-GBM) disease has been reported. Whether circulating IgA anti-GBM antibodies affect the clinico-pathologic characteristics and outcome of typical anti-GBM disease deserves further study. Methods: Circulating IgA anti-α3(IV)NC1 antibodies were examined by enzyme-linked immunosorbent assay (ELISA) using recombinant human α3(IV)NC1 as solid phase antigens in 107 patients with anti-GBM disease and 115 controls. Clinical, pathological, and follow-up data of patients were retrospectively analyzed. Results: Circulating IgA anti-α3(IV)NC1 antibodies were found in 18.7% (20/107) of patients with anti-GBM disease but were not detected in healthy controls or in patients with other glomerular diseases. The positivity of circulating IgA anti-α3(IV)NC1 antibodies was not associated with whether the patient was with combined IgA nephropathy or other glomerulonephritis. Kidney immunofluorescence showed no statistical difference in IgA deposition between patients with circulating IgA anti-α3(IV)NC1 antibodies and patients without (30.0% vs. 40.4%, P = 0.725). The titers of circulating immunoglobulin G (IgG) anti-α3(IV)NC1 antibodies in patients with circulating IgA anti-α3(IV)NC1 antibodies were significantly higher than those without (200 [183.3, 200] vs. 161 [85.5, 200] U/ml, P = 0.005). There were no significant differences in kidney outcome and mortality between the 2 groups. Conclusion: Circulating IgA anti-α3(IV)NC1 antibodies occurred in 18.7% (20/107) of patients with anti-GBM in our center and were specific to anti-GBM disease. Patients with circulating IgA anti-α3(IV)NC1 antibodies showed a higher levels of serum IgG anti-α3(IV)NC1 antibodies than those without.

Effect of Miscellaneous Meal Replacements for Soybean Meal on Growth Performance, Serum Biochemical Parameters, and Gut Microbiota of 50-75 kg Growing Pigs.

This study was carried out to investigate the effects of miscellaneous meal (rapeseed meal, cottonseed meal, and sunflower seed meal) as a replacement for soybean meal on growth performance, apparent nutrient digestibility, serum biochemical parameters, serum free amino acid contents, and gut microbiota of 50-75 kg growing pigs. A total of 54 healthy growing pigs (Duroc × Landrace × Yorkshire) with initial body weights (BWs) of 50.64 ± 2.09 kg were randomly divided into three treatment groups, which included the corn-soybean meal group (CON), corn-soybean-miscellaneous meal group (CSM), and corn-miscellaneous meal group (CM). Each treatment included six replicates with three pigs in each replicate. Dietary protein levels were maintained at 15% in all three treatment groups. Additional rapeseed meals, cottonseed meals, and sunflower seed meals were added to the CSM group's meals to partially replace the 10.99% soybean meal in the CON group in a 1:1:1 ratio. Pigs in the CM group were fed a diet with a mixture of miscellaneous meals (7.69% rapeseed meal, 7.69% cottonseed meal, and 7.68% sunflower seed meal) to totally replace soybean meal. Our findings revealed that there was no significant impact of replacing soybean meal with miscellaneous meal on the ADG (average daily gain), ADFI (average daily feed intake), or F/G (feed-to-gain ratio) (p > 0.05) of growing pigs weighing 50-75 kg, nor on the crude protein, crude fat, or gross energy (p > 0.05) of the diet. On the other hand, compared to the CON group, the CM group exhibited significantly elevated serum alanine aminotransferase (ALT) and triglyceride (TG) levels (p < 0.05), while urea levels were significantly reduced (p < 0.05). No significant effect was observed on the serum free amino acid contents (p > 0.05) following the substitution of soybean meal with miscellaneous meal. A t-test analysis indicated that compared with the CON group, the CM group exhibited a significantly diminished abundance of Euryachaeota at the phylum level and augmented abundance of Desulfobacterota at the genus level. This study demonstrated that the miscellaneous meals (rapeseed meal, cottonseed meal, and sunflower seed meal) as a substitute for soybean meal in the diet had no significant negative effects on the growth performance, apparent nutrient digestibility, serum amino acid content, or diversity of fecal microbiota in 50-75 kg growing pigs. These results can be helpful in developing further miscellaneous meals (rapeseed meal, cottonseed meal, and sunflower seed meal) as functional alternative feed ingredients to soybean meal in pig diets.

Autoantibodies against laminin-521 are pathogenic in anti-glomerular basement membrane disease.

Anti-glomerular basement membrane (anti-GBM) disease is an organ-specific autoimmune disorder characterized by autoantibodies against GBM components. Evidence from human inherited kidney diseases and animal models suggests that the α, ß, and γ chains of laminin-521 are all essential for maintaining the glomerular filtration barrier. We previously demonstrated that laminin-521 is a novel autoantigen within the GBM and that autoantibodies to laminin-521 are present in about one-third of patients. In the present study, we investigated the pathogenicity of autoantibodies against laminin-521 with clinical and animal studies. Herein, a rare case of anti-GBM disease was reported with circulating autoantibodies binding to laminin-521 but not to the NC1 domains of α1-α5(IV) collagen. Immunoblot identified circulating IgG from this patient bound laminin α5 and γ1 chains. A decrease in antibody levels was associated with improved clinical presentation after plasmapheresis and immunosuppressive treatments. Furthermore, immunization with laminin-521 in female Wistar-Kyoto rats induced crescentic glomerulonephritis with linear IgG deposits along the GBM, complement activation along with infiltration of T cells and macrophages. Lung hemorrhage occurred in 75.0% of the rats and was identified by the presence of erythrocyte infiltrates and hemosiderin-laden macrophages in the lung tissue. Sera and kidney-eluted antibodies from rats immunized with laminin-521 demonstrated specific IgG binding to laminin-521 but not to human α3(IV)NC1, while the opposite was observed in human α3(IV)NC1-immunized rats. Thus, our patient data and animal studies imply a possible independent pathogenic role of autoantibodies against laminin-521 in the development of anti-GBM disease.

Glutamine protects intestinal immunity through microbial metabolites rather than microbiota.

Glutamine has anti-inflammatory properties as well as the ability to maintain the integrity of the intestinal barrier. In our previous study, we found that 1.0% glutamine promoted SIgA (secretory immunoglobulin A) synthesis in the gut via both T cell-dependent and non-dependent processes, as well as via the intestinal microbiota. The purpose of this study was to investigate whether the intestinal microbiota or microbial metabolites regulate SIgA synthesis. In the mouse model, supplementation with 1.0% glutamine had no significant effect on the intestinal microbiota, but KEGG function prediction showed the difference on microbiota metabolites. Therefore, in this study, untargeted metabolomics techniques were used to detect and analyze the metabolic changes of glutamine in intestinal luminal contents. Metabolomics showed that in the positive ion (POS) mode, a total of 1446 metabolic differentials (VIP ≥ 1, P < 0.05, FC ≥ 2 or FC ≤ 0.5) were annotated in samples treated with glutamine-supplemented group compared to control group, of which 922 were up-regulated and 524 down-regulated. In the negative ion (NEG) mode, 370 differential metabolites (VIP ≥ 1, P < 0.05, FC ≥ 2 or FC ≤ 0.5) were screened, of which 220 were up-regulated and 150 down-regulated. These differential metabolites mainly include bile secretion synthesis, ABC transporters, diterpenoids and other secondary metabolites. KEGG analysis showed that propionic acid metabolism, TCA cycle, endoplasmic reticulum protein processing, nitrogen metabolism and other metabolic pathways were active. The above metabolic pathways and differential metabolites have positive effects on intestinal development and intestinal immunity, and combined with our previous studies, we conclude that glutamine supplementation can may maintain intestinal homeostasis and improving intestinal immunity through intestinal microbial metabolites.

Taurine alleviates oxidative stress in porcine mammary epithelial cells by stimulating the Nrf2-MAPK signaling pathway.

The high incidence of oxidative stress in sows during late gestation and lactation affects mammary gland health, milk yield, and milk quality. Recently, we found that supplementing maternal diets with 1% taurine improved antioxidant capability and enhanced growth performance in offspring; however, the mechanisms underlying these are unknown. This study aimed to investigate the cytoprotective effects and the mechanism of taurine in mitigating oxidative stress in porcine mammary epithelial cells (PMECs). PMECs were pretreated with 0-2.0 mM taurine for 12 h and then subjected to oxidative injury with 500 µM hydrogen peroxide (H2O2). Pretreatment with taurine attenuated decreased cell viability, enhanced superoxide dismutase, and reduced the intracellular reactive oxygen species accumulation after H2O2 exposure. Taurine also prevented H2O2-induced endoplasmic reticulum stress. Nuclear factor erythroid 2-related factor 2 (Nrf2) was essential to the cytoprotective effects of taurine on PMECs, as Nrf2 knockdown significantly inhibited taurine-induced cytoprotection against oxidative stress. Moreover, we confirmed that Nrf2 induction by taurine was mediated through the inactivation of the p38/MAPK pathway. Overall, taurine supplementation has beneficial effects on redox balance regulation and may protect against oxidative stress in lactating animals.

Dietary dibutyryl cAMP supplementation regulates the fat deposition in adipose tissues of finishing pigs via cAMP/PKA pathway.

This study investigated potential mechanism of dibutyryl-cAMP (db-cAMP) on porcine fat deposition. (1) Exp.1, 72 finishing pigs were allotted to 3 treatments (0, 10 or 20 mg/kg dbcAMP) with 6 replicates. dbcAMP increased the hormone sensitive lipase (HSL) activity and expression of ß-adrenergic receptor (ß-AR) and growth hormone receptor (GHR), but decreased expression of peroxisome proliferator-activated receptor gamma 2 (PPAR-γ2) and adipocyte fatty acid binding protein (A-FABP) in back fat. dbcAMP upregulated expression of ß-AR, GHR, PPAR-γ2 and A-FABP, but decreased insulin receptor (INSR) expression in abdominal fat. Dietary dbcAMP increased HSL activity and expression of G protein-coupled receptor (GPCR), cAMP-response element-binding protein (CREB) and insulin-like growth factor-1 (IGF-1), but decreased fatty acid synthase (FAS) and lipoprotein lipase (LPL) activities, and expression of INSR, cAMP-response element-binding protein (C/EBP-α) and A-FABP in perirenal fat. (2) Exp. 2, dbcAMP suppressed the proliferation and differentiation of porcine preadipocytes in a time- and dose-dependent manner, which might be associated with increased activities of cAMP and protein kinase A (PKA), and expression of GPCR, ß-AR, GHR and CREB via inhibiting C/EBP-α and PPAR-γ2 expression. Collectively, dbcAMP treatment may reduce fat deposition by regulating gene expression related to adipocyte differentiation and fat metabolism partially via cAMP-PKA pathway.

Comparative Transcriptome Analysis of the Skin and the Peritoneal Wall Layer of Triplophysa stenura Distributed in High Elevations.

A total of 81,868 All-Unigenes were sequenced and assembled by the transcriptome in the dorsal skin, the lateral skin, and the peritoneal wall layer of Triplophysa stenura with a total assembly length of 123,827,585 bp, and 68,750 unigenes were annotated to seven functional databases. A total of 588 DEGs were screened between the dorsal and lateral skin, 17,097 DEGs were screened between the dorsal skin and the peritoneal wall layer, and 16,598 DEGs were screened between the lateral skin and the peritoneal wall layer. Most of DEGs in three tissues were annotated to GO terms related to cellular structures, binding, cellular processes, and catalytic activity. They were also annotated to KEGG pathways such as the MAPK signaling pathway, PI3K-Akt signaling pathway, Wnt signaling pathway, melanogenesis, tyrosine metabolism, and cell cycle. A total of twenty-three DEGs were found to be enriched in the melanin synthesis pathway by a local Blast comparison, of which nine DEGs were significantly upregulated in the peritoneal wall layer and six DEGs were significantly upregulated in the dorsal and lateral skin. The results suggest that these genes may be associated with the molecular mechanism of melanin synthesis in T. stenura, and the differential regulation of genes may be related to the differences in UVR intensity and tissue sites of melanin synthesis. Further investigation is needed on how these genes specifically regulate melanin synthesis.

Effect of Resveratrol Supplementation on Intestinal Oxidative Stress, Immunity and Gut Microbiota in Weaned Piglets Challenged with Deoxynivalenol.

(1) Background: Deoxynivalenol (DON) is a general mycotoxin that induces severe intestinal barrier injury in humans and animals. Resveratrol (RES) efficiently exerts anti-inflammatory and antioxidant effects. However, the information regarding RES protecting against DON-induced oxidative stress and intestinal inflammation in piglets is limited. (2) Methods: A total of 64 weaned piglets (Duroc × (Landrace × Yorkshire), 21-d-old, barrow) were randomly allocated to four groups (eight replicate pens per group, each pen containing two piglets) for 28 d. The piglets were fed a control diet (CON) or the CON diet supplemented with 300 mg RES/kg diet (RES group), 3.8 mg DON/kg diet (DON) or both (DON+RES) in a 2 × 2 factorial design. (3) Compared with unsupplemented DON-challenged piglets, RES supplementation in DON-challenged piglets increased ileal villus height and the abundance of ileal SOD1, GCLC and PG1-5 transcripts and Muc2 protein (p < 0.05), while decreasing the mRNA and proteins expression of ileal IL-1ß, IL-6 and TNF-α, and malondialdehyde (MDA) levels in plasma and ileum in DON-challenged piglets (p < 0.05). Moreover, the abundances of class Bacilli, order Lactobacillales, family Lactobacillaceae and species Lactobacillus gasseri were increased in DON-challenged piglets fed a RES-supplemented diet compared with those in DON-challenged piglets(p ≤ 0.05). (4) Conclusions: our results indicated that RES supplementation in DON-challenged piglets efficiently attenuated intestinal inflammation and oxidative stress and improved gut microbiota, thereby alleviating DON-induced intestinal barrier injury.

Niacin Improves Intestinal Health through Up-Regulation of AQPs Expression Induced by GPR109A.

(1) Background: Changes in the expression of aquaporins (AQPs) in the intestine are proved to be associated with the attenuation of diarrhea. Diarrhea is a severe problem for postweaning piglets. Therefore, this study aimed to investigate whether niacin could alleviate diarrhea in weaned piglets by regulating AQPs expression and the underlying mechanisms; (2) Methods: 72 weaned piglets (Duroc × (Landrace × Yorkshire), 21 d old, 6.60 ± 0.05 kg) were randomly allotted into 3 groups for a 14-day feeding trial. Each treatment group included 6 replicate pens and each pen included 4 barrows (n = 24/treatment). Piglets were fed a basal diet (CON), a basal diet supplemented with 20.4 mg niacin/kg diet (NA) or the basal diet administered an antagonist for the GPR109A receptor (MPN). Additionally, an established porcine intestinal epithelial cell line (IPEC-J2) was used to investigate the protective effects and underlying mechanism of niacin on AQPs expression after Escherichia coli K88 (ETEC K88) treatment; (3) Results: Piglets fed niacin-supplemented diet had significantly decreased diarrhea rate, and increased mRNA and protein level of ZO-1, AQP 1 and AQP 3 in the colon compared with those administered a fed diet supplemented with an antagonist (p < 0.05). In addition, ETEC K88 treatment significantly reduced the cell viability, cell migration, and mRNA and protein expression of AQP1, AQP3, AQP7, AQP9, AQP11, and GPR109A in IPEC-J2 cells (p < 0.05). However, supplementation with niacin significantly prevented the ETEC K88-induced decline in the cell viability, cell migration, and the expression level of AQPs mRNA and protein in IPEC-J2 cells (p < 0.05). Furthermore, siRNA GPR109A knockdown significantly abrogated the protective effect of niacin on ETEC K88-induced cell damage (p < 0.05); (4) Conclusions: Niacin supplementation increased AQPs and ZO-1 expression to reduce diarrhea and intestinal damage through GPR109A pathway in weaned piglets.

Rituximab for the treatment of refractory anti-glomerular basement membrane disease.

BACKGROUND: Anti-glomerular basement membrane (anti-GBM) disease is a rare but severe autoantibody-mediated immune disorder. The typical clinical presentation includes rapidly progressive glomerulonephritis and often concurrent pulmonary hemorrhage. The present study is aimed to investigate the therapeutic effects of rituximab either used alone or with other immunosuppressants. METHODS: Eight patients diagnosed with anti-GBM disease and treated with rituximab from 2014 to 2020 were retrospectively reviewed. RESULTS: Eight patients included 5 males and 3 females with a median age of 58.5 years. They all presented severe kidney injuries and 1 patient had lung hemorrhage. At diagnosis, the median of serum creatinine was 246 µmol/L (ranging from 91 to 850 µmol/L), with 3 patients requiring dialysis. All of them received corticosteroids and plasmapheresis. Rituximab was given as either standard four weekly doses or one pulse ranging from 100 to 600 mg. After a median follow-up of 34.5 months, kidney function was partially recovered or stabilized in 5/8 (62.5%) patients, free of dialysis. Anti-GBM antibodies remained undetected in all patients during follow-up. No severe adverse effect associated with rituximab was observed. CONCLUSION: Rituximab may be an alternative therapy in the treatment of patient with severe or refractory anti-GBM disease.

Low Protein Diet Improves Meat Quality and Modulates the Composition of Gut Microbiota in Finishing Pigs.

This study investigated the effect of a low protein (LP) diet on growth performance, nitrogen emission, carcass traits, meat quality, and gut microbiota in finishing pigs. Fifty-four barrows (Duroc × Landrace × Yorkshire) were randomly assigned to three treatments with six replicates (pens) of three pigs each. The pigs were fed with either high protein (HP, 16% CP), medium protein (MP, 12% CP), and LP diets (10% CP), respectively. The LP diets did not influence the growth performance, but significantly decreased the plasma urea nitrogen contents and fecal nitrogen emission (P < 0.05). The LP diet significantly decreased the plasma contents of malondialdehyde (MDA) and increased the plasma glutathione (GSH) contents (P < 0.05). The LP diets significantly increased the backfat thickness at the first and last ribs, L* (lightness) value of meat color, and muscle fiber density in the longissimus dorsi (P < 0.05). The messenger RNA (mRNA) expression of fatty acid synthetase (FAS), peroxisome proliferator-activated receptor-gamma (PPARγ), leptin, and acetyl-CoA carboxylase (ACC) was significantly downregulated, while that of carnitine palmitoyltransferase 1 (CPT1) and myosin heavy chain (MYHC) IIx in the longissimus Dorsi muscle was significantly upregulated by LP diets (P < 0.05). The 16S sequencing analysis showed that the abundance of unidentified Bacteria at the phylum level, and Halanaerobium and Butyricicoccusat at the genus level in the colonic digesta were significantly decreased by LP diet (P < 0.05). The LP diet significantly decreased the observed species of α-diversity in both ileal and colonic microbiota (P < 0.05). Spearman correlation analysis identified a significant positive correlation between the abundance of the ileal genera Streptococcus and L* value at 24 and 48 h, and a significant negative correlation between unidentified_Ruminococcasceae in both ileum and colon with L* value at 24 h (P < 0.05). Collectively, the LP diet supplemented with lysine, methionine, threonine, and tryptophan could reduce the fecal nitrogen emission without affecting growth performance and improve meat quality by regulating the antioxidant capacity and gene expression involved in fat metabolism as well as modulating the gut microbiota composition in finishing pigs.

The Responses of Lactobacillus reuteri LR1 or Antibiotic on Intestinal Barrier Function and Microbiota in the Cecum of Pigs.

This study aimed to investigate responses of the Lactobacillus reuteri or an antibiotic on cecal microbiota and intestinal barrier function in different stages of pigs. A total of 144 weaned pigs (Duroc × Landrace × Yorkshire, 21 days of age) were randomly assigned to the control group (CON, fed with a basal diet), the antibiotic group (AO, fed with basal diet plus 100 mg/kg olaquindox and 75 mg/kg aureomycin), and the L. reuteri group (LR, fed with the basal diet + 5 × 1010 CFU/kg L. reuteri LR1) throughout the 164-d experiment. A total of 45 cecal content samples (5 samples per group) from different periods (14th, 42th, and 164th days) were collected for 16S rRNA gene amplification. The results revealed that although LR and AO did not change the diversity of cecal microbiota in pigs, the abundance of some bacteria at the genus level was changed with age. The proportion of Lactobacillus was increased by LR in early life, whereas it was decreased by AO compared with the control group. The relative abundance of Ruminococcaceae was increased along with age. In addition, the gas chromatography results showed that age, not AO or LR, has significant effects on the concentrations of SCFAs in the cecum of pigs (P < 0.05). However, the mRNA expression of tight junction proteins zonula occluden-1 (ZO-1) and occludin were increased by AO in the cecum of pigs on day 14, while LR increased the mRNA expression of intestinal barrier-related proteins ZO-1, occludin, mucin-1, mucin-2, PG1-5, and pBD2 in the cecum of pigs on days 14 and 164 (P < 0.05). In conclusion, LR and AO have different effects on the intestinal barrier function of the cecum, and neither LR nor AO damaged the intestinal barrier function of pig cecum. In addition, LR and AO have little effects on cecal microflora in different stages of the pigs. The microflora and their metabolite SCFAs were significantly changed along with age. These findings provide important information to understand the homeostasis of the cecum of pigs after antibiotic or probiotic treatment.

Effects of early sub-therapeutic antibiotic administration on body tissue deposition, gut microbiota and metabolite profiles of weaned piglets.

BACKGROUND: This study aimed to evaluate the effects of sub-therapeutic antibiotic (STA) administration and its subsequent withdrawal on the body tissue deposition, gut microbiota, and metabolite profiles of piglets. The piglets in the experimental group were fed with STA (30 mg kg-1 bacitracin methylene disalicylate, 75 mg kg-1 chlortetracycline, 300 mg kg-1 calcium oxytetracycline) for 14 days and the target bodyweight of the withdrawal period was 25 kg. RESULTS: The experiment was divided into two periods: the administration period and the withdrawal period. The results showed that STA did not improve piglets' growth performance during the two periods. Piglets treated with STA had lower body water deposition during the withdrawal period and tended to increase body lipid deposition during the withdrawal period and the whole period in comparison with the piglets in the control group. It was found that STA markedly altered the colonic microbiota and their metabolites in the piglets. Sub-therapeutic antibiotics were initially effective in decreasing the abundance of pathogenic bacteria during the administration period; however, STA could not continue the effect during the withdrawal period, leading to a rebound of pathogenic bacteria such as Alloprevotella and the increased abundance of other pathogenic bacteria like Oscillibacter. Remarkably, STA treatment decreased Blautia abundance. This bacterium plays a potential protective role against obesity. Metabolomic analysis indicated that STA mainly altered amino acid metabolism, lipid metabolism, and carbohydrate metabolism during the two periods. Spearman's correlation analysis showed that the gut microbiota was highly correlated with microbial metabolite changes. CONCLUSION: These results suggest that early STA administration may alter body tissue deposition later in life by reshaping the gut microbiota and their metabolite profiles. © 2022 Society of Chemical Industry.

Intestinal morphology and immune profiles are altered in piglets by early-weaning.

This study was to investigate the developmental changes in intestinal morphology and immune profiles in suckling and weaning piglets. Seventy-two weaning piglets with equal initial body weight from 8 litters (Duroc × Landrace × Yorkshire, 9 piglets per litter) were selected. Thirty-two piglets in the suckling group were nursed by sows until they were 17, 21, 28, or 35 days of age. While the other forty piglets were weaned at 14 d of age, and then housed in the same farrowing cage without a sow and slaughtered until they were on d 0, 3, 7, 14 and 21 after weaning at d 14 of age (wd 0, 3, 7, 14, 21). Blood, jejunal mucosa, intraepithelial lymphocyte (IEL) and lamina propria T lymphocyte (LPL) were harvested from suckling piglets at d 14, 17, 21, 28 and 35 of age and weaning piglets on d 0, 3, 7, 14 and wd 0, wd 3, wd 7, wd 14 and wd 21). The results showed that compared with the wd 0, early weaning significantly declined the average daily gain of postweaning 0-7 (wd 0-7) (P < 0.05), and jejunal villus height on wd 3 (P < 0.05), as well as increased the jejunal crypt depth of piglets on wd 7, 14 and 21 (P < 0.05). And there were no significant differences in average daily gain and villus height after suckling (P > 0.05). The level of serum interferon-γ (IFN-γ) was increased on wd 7 and decreased on wd 21 (P < 0.05), while IFN-γ level in jejunal mucosa was enhanced at wd 3 in comparison with wd 0 (P < 0.05). And the serum interleukin-4 (IL-4) levels were increased at wd 14, wd 21, but the mucosa IL-4 concentration was strikingly increased on wd 7 (P < 0.05). Moreover, weaning led to the enhanced levels of interleukin-1b (IL-1b), interleukin-2 (IL-2) and soluble interleukin-2 receptor (sIL-2R) in serum (P < 0.05), as well as declined the levels of sIL-2R in jejunal mucosa at wd 3 (P < 0.05). In suckling piglets, the serum immunoglobulin A (IgA), IL-4 and IL-2 levels were increased with increasing age (P < 0.05), whereas the jejunal mucosa IL-1b and serum sIL-2R levels were lower (P < 0.05). Furthermore, significantly lower CD4 percentage in peripheral blood T lymphocyte subsets were found at wd 3 and wd 7 (P < 0.05), whereas the CD8 percentage in peripheral blood T lymphocyte subsets were enhanced on wd 3 and wd 7 than wd 0 (P < 0.05). Moreover, the weaning piglets at wd 3 had a lower CD4/CD8 ratio than wd 0 (P < 0.05). Additionally, we found that weaning decreased IgG, IL-4, IL-2 and IL-1b levels of IEL during 1-week post-weaning (P < 0.05). Similarly, the levels of IgA, IgG, IL-2 and sIL-2R in LPL medium were also declined from piglets postweaning 1 week (P < 0.05). Early weaning reduced the growth performance, damaged jejunal morphology, disrupted IFN-γ/IL-4, IL-2/sIL-2R and T lymphocyte balance, and impaired the IEL and LPL immune profiles of piglets.

[Distribution and comparison of melanin in different tissues and organs of Triplophysa stenura and T. orientalis]. / ç»†å°¾é«˜åŽŸé³ å’Œä¸œæ–¹é«˜åŽŸé³ ä¸åŒç»„ç»‡å™¨å®˜é»‘è‰²ç´ çš„åˆ†å¸ƒå’Œæ¯”è¾ƒ.

We examined the distribution characteristics of melanin in different tissues and organs of Triplophysa stenura and T. orientalis by using histological method. The results showed that melanin was distributed in the head skin, dorsal skin, lateral skin, peritoneal kidney layer, spinal cord cavity wall, peritoneal wall layer, pericardial cavity wall, neurocranial cavity wall and eyes of both Triplophysa species. Melanin was not found in the abdomen skin, liver chorion, gonad capsule and spleen capsule. Melanin was distributed in the dermis layer and subcutaneous layer in the skin, and in the endothelial layer or wall layer in other tissues and organs. Melanin was mainly distributed on the back, with sparse and symmetrical distribution on both sides of the body. Melanin was more abundant and densely distributed on the dorsal and lateral skin with stripes than areas without stripes. Melanin in the no stripes skin was only partially aggregated or formed intermittently distributed melanin patches. The distribution of melanin in different tissues and organs of the same Triplophysa species was different, and the percentage of distribution area and thickness of melanin layer were significantly different. However, the distribution characteristics of melanin in the same tissues and organs were similar in two Triplophysa species. The distribution of melanin in the tissues and organs of both species were related to the intensity of ultraviolet radiation they received, which was an adaptation to the intense ultraviolet radiation environment of the plateau.

Meta-analysis of energy intake of growing-finishing pigs in China.

Data from 655 treatments of 116 studies were used in a meta-analysis to determine the daily digestible energy (DE), metabolizable energy (ME) and net energy (NE) intake of Chinese growing-finishing pigs, and to predict feed efficiency responses to change in dietary DE, ME and NE. Three alternative functions (i.e., polynomial, Bridges and asymptotic function) were employed for fitting daily DE, ME or NE intakes to mean body weight. The results showed that the three models from the current study provided reasonable fit (all R2  > 0.83) for the energy intake data. However, under the same energy system, the polynomial function had the smallest Akaike's information criteria (AIC) and residual standard deviation (RSD), followed by Bridges and asymptotic functions. The three model-generated energy intakes of growing pigs were significantly less than that of the Chinese Feeding Standard of Swine, but similar to that of the National Research Council (2012), while the values of finishing pigs were greater than both standards. Compared with those that predict feed efficiency based on DE or ME, the equation with NE as a predictor had the minimized AIC and RSD. It was also found that feed efficiency increased with increasing dietary energy density (DED), but this response varied with pig body weight, and the lighter pigs were more sensitive to DED than heavier pigs.