Effects of different concentrations of coated nano zinc oxide material on fecal bacterial composition and intestinal barrier in weaned piglets.

BACKGROUND: Coated nano zinc oxide (Cnz) is a new feed or food additive, which is a potential replacement for a pharmacological dose level of ZnO. This study evaluated the positive effects of different concentrations of Cnz on the intestinal bacterial core, enterobacterial composition and mucosal barrier function in a pig model. RESULTS: Microbiota sequencing results showed that Cnz could significantly alter the intestinal microbiota composition and metabolism. Besides increasing the richness indices (ACE and Chao1), 10% Cnz could protect the intestinal mucosal barrier through increasing the expression of occludin and zonula occludens-1 in the small intestine, increase the abundance of Lachnospiraceae UCG-004 and decrease the abundance of Ruminococcus flavefaciens compared to high ZnO diet and 5% Cnz material. CONCLUSIONS: Cnz material at 10% supplementation is more effective than a level of 5% Cnz in increasing intestinal barrier through affecting gut microbiota. © 2020 Society of Chemical Industry.

Gut microbiota and blood metabolomics in weaning multiparous sows: Associations with oestrous.

This study was conducted to detect the potential relationship between changed plasma metabolites, intestinal microbiota and the weaning-to-oestrous interval in multiparous sows after weaning. Multiparous sows were allocated to two groups after weaning: the oestrous group (n = 15) with a weaning-to-oestrous interval ≤7 days or the anoestrous group (n = 15) with a weaning-to-oestrous interval >14 days. The levels of plasma reproductive hormones: oestradiol, follicle-stimulating hormone and luteinizing hormone, plasma total protein; blood urea nitrogen; cholesterol; high-density lipoprotein; and ammonia (NH3 ) were significantly lower in the anoestrous sows compared with the oestrous sows (p < .05). The plasma metabolomics analysis identified 14 metabolites (lactose, l-cysteine, cytosine, hydantoin, palmitoleic acid, arachidic acid, linoleic acid methyl ester, α-ketoglutaric acid, N(ε)-trimethyllysine, threo-ß-hydroxyaspartate, 3-(3-hydroxyphenyl) propionic acid and others) with lower concentrations and 12 metabolites (noradrenaline, 5-dihydrocortisone, p-cresol, 1,4-cyclohexanedione, 2,3-dimethylsuccinic acid and others) with higher concentrations in the anoestrous group compared with the oestrous group (p < .05). The 16S rRNA pyrosequencing analysis showed the relative increase in abundance of the Prevotella and the Bacteroides at the genus level in the anoestrous group (p < .05). At the phylum level, lower proportions of Firmicutes and Lentisphaerae were observed in the anoestrous group (p < .05). This study provided a comprehensive assessment of metabolic differences in the blood and differences in the gut microbiome composition between anoestrous and oestrous sows. And suggesting that this profiling approach may offer new insights into explaining the alteration of the gut microbiota and blood metabolomics are correlated with sex hormone secretion and the weaning-to-oestrous interval of sows after weaning.

Influence of supplemented coated-cysteamine on morphology, apoptosis and oxidative stress status of gastrointestinal tract.

BACKGROUND: Cysteamine was coated to cover its odor and maintain the stability. However, coated cysteamine (CC) has not been clearly evaluated for its effects on the gastrointestinal mucosa status. We hypothesize that the appropriate CC supplementation in diet impacts the stomach and intestinal mucosa variously through regulating the morphology, apoptosis, and oxidative stress status in model of pigs. RESULTS: The results showed that villus height increased (P < 0.05), and crypt depth decreased (P < 0.05) in the ileum when pigs were fed the diet with low cysteamine (LCS) compared with the control diet. The ileal lesion score in the LCS group was significantly (P < 0.01) lower than that in the control group, while the gastric lesion score in the CC group was significantly (P < 0.01) higher compared with that of the control group. It also showed that the activities of total superoxide dismutase (T-SOD) and diamine oxidase (DAO) were upregulated (P < 0.05) in the LCS group. In addition, Bax and caspase 3 immunore-activity increased (P < 0.01), and Bcl-2 immunoreactivity decreased (P < 0.01) in the gastric mucosa of pigs fed the diet with high cysteamine (HCS). The Bax and caspase 3 immunoreactivity decreased (P < 0.01), and Bcl-2 immunoreactivity increased (P < 0.01) in ileum mucosa of pigs fed the HCS diet. CONCLUSIONS: Although moderate dietary coated cysteamine showed positive effects on GI mucosal morphology, apoptosis, and oxidative stress status, the excess coated cysteamine may cause apoptosis leading to GI damage in pigs.

Negative effects on newborn piglets caused by excess dietary tryptophan in the morning in sows.

BACKGROUND: This study investigated the effect of dynamic feeding models of dietary tryptophan on sows' performance during late pregnancy. RESULTS: The average piglet birth weight and live farrowing rate from sows consuming a high-low tryptophan diet (0.39% Trp in the morning and 0.13% Trp in the afternoon) were decreased compared with those fed a 2×tryptophan diet (0.26% Trp in the morning and afternoon). Compared with the 2×tryptophan group, sow serum kynurenic acid and the newborn liver n-6:n-3 polyunsaturated fatty acid ratio were significantly higher, and sow serum taurine and newborn serum taurine, phosphoserine, cysteine and proline were lower in the high-low tryptophan diet group. Eighty-eight genes were differentially expressed in newborn piglets' livers between the 2×tryptophan and high-low groups. Genes related to cytotoxic effector regulation (major histocompatibility complex class I proteins), NADH oxidation, reactive oxygen species (ROS) metabolism and tissue development were differentially expressed between these two groups. CONCLUSION: Together, the results provide information on new biomarkers in serum or liver and provide novel insights into variations in the fetal liver during exogenous stimulus response and biological processes of ROS metabolism in fetuses during late pregnancy caused by a single excessive tryptophan ingestion daily in the morning. © 2018 Society of Chemical Industry.

Effects of coated cysteamine hydrochloride on muscle fiber characteristics and amino acid composition of finishing pigs.

Objective: This experiment was designed to determine the effects of coated cysteamine hydrochloride (CC) on muscle fiber characteristics, amino acid composition and transporters gene expression in the longissimus dorsi muscle (LDM) of finishing pigs. Methods: Two hundred and sixteen Duroc/Landrace/Yorkshire cross-bred male finishing pigs were fed with a corn-soybean basal diet supplemented with 0, 70 and 140 mg/kg cysteamine. Each group contained eight replicates of nine pigs per replicate. After 29 days, one pig was randomly selected from each replicate and slaughtered. Blood and LDM samples were collected and analyzed. Results: The results showed that supplemental dietary CC increased (P < 0.05) the muscle fiber density. And CC supplementation also up-regulated (P < 0.05) the expression of MyHC1 and MyHC2x mRNA levels, and down-regulated (P < 0.05) MyHC2b expression in the LDM. Additionally, supplemental dietary CC reduced (P < 0.05) the concentration of total cholesterol in the plasma and enhanced (P < 0.05) the concentrations of essential amino acid and total amino acid in the LDM. The relative expression levels of CAT2, b0,+AT, and y+LAT1 were up-regulated (P < 0.05) in the LDM when pigs were fed with the dietary CC of 70 mg/kg. Conclusion: Cysteamine supplementation could increase fiber density and distribution of fiber types. It also improved the deposition of protein in the LDM by up-regulated the expression of amino acid transporters.

Effects of dietary coated cysteamine hydrochloride on pork color in finishing pigs.

BACKGROUND: Coated cysteamine hydrochloride (CC) was applied as a feed additive in animal production. The influence and the mechanisms of CC used as a feed additive in promoting meat quality in finishing pigs were investigated. RESULTS: Dietary CC supplementation increased (P < 0.05) the a* and H* values and reduced (P < 0.05) the L* value in the longissimus dorsi muscles at 48 h postmortem (P < 0.05). The deoxymyoglobin content was enhanced (P < 0.05) and the metmyoglobin and malondialdehyde contents were reduced (P < 0.05) in pigs fed the dietary CC. Pigs fed a dietary CC of 0.035 g kg-1 had a lower cooking loss (P < 0.05) and a higher a* (24 h) value in the longissimus dorsi muscles than pigs on control treatment. The messenger RNA expression of superoxide dismutase 1 was upregulated (P < 0.05) in the longissimus dorsi. CONCLUSION: Dietary supplementation with CC could improve antioxidant status and delay meat discoloration by improving glutathione levels and antioxidase activity after longer chill storage (for 48 h after slaughter). Dietary supplementation with CC at 0.035 g kg-1 may promote the stability of pork color by reducing oxidation. © 2017 Society of Chemical Industry.

A review of the immunomodulatory role of dietary tryptophan in livestock and poultry.

Tryptophan, a nutritionally essential amino acid, is active in the regulation of immune responses in animals. The products of tryptophan metabolism, such as indoleamine 2,3-dioxygenase, kynurenine, quinolinic acid, and melatonin, may improve immunity in an organism and induce anti-inflammatory responses. The immune tolerance processes mediated by tryptophan metabolites are not well understood. Recent studies have reported that the enzymes that break down tryptophan through the kynurenine metabolic pathway are found in numerous cell types, including immunocytes. Moreover, some tryptophan metabolites have been shown to play a role in the inhibition of T lymphocyte proliferation, elevation of immunoglobulin levels in the blood, and promotion of antigen-presenting organization in tissues. This review summarizes the effects and mechanisms of tryptophan and metabolites in immune functions in livestock and poultry. It also highlights the areas in which our understanding of the role(s) of tryptophan is incomplete and suggests possible future research that might prove of benefit to livestock and poultry producers.

An LRP16-containing preassembly complex contributes to NF-κB activation induced by DNA double-strand breaks.

The activation of NF-κB has emerged as an important mechanism for the modulation of the response to DNA double-strand breaks (DSBs). The concomitant SUMOylation and phosphorylation of IKKγ by PIASy and ATM, respectively, is a key event in this mechanism. However, the mechanism through which mammalian cells are able to accomplish these IKKγ modifications in a timely and lesion-specific manner remains unclear. In this study, we demonstrate that LRP16 constitutively interacts with PARP1 and IKKγ. This interaction is essential for efficient interactions among PARP1, IKKγ, and PIASy, the modifications of IKKγ, and the activation of NF-κB following DSB induction. The regulation of LRP16 in NF-κB activation is dependent on the DSB-specific sensors Ku70/Ku80. These data strongly suggest that LRP16, through its constitutive interactions with PARP1 and IKKγ, functions to facilitate the lesion-specific recruitment of PARP1 and IKKγ and, ultimately, the concomitant recruitment of PIASy to IKKγ in response to DSB damage. Therefore, the study has provided important new mechanistic insights concerning DSB-induced NF-κB activation.

Redox Properties of Tryptophan Metabolism and the Concept of Tryptophan Use in Pregnancy.

During pregnancy, tryptophan (Trp) is required for several purposes, and Trp metabolism varies over time in the mother and fetus. Increased oxidative stress (OS) with high metabolic, energy and oxygen demands during normal pregnancy or in pregnancy-associated disorders has been reported. Taking the antioxidant properties of Trp and its metabolites into consideration, we made four hypotheses. First, the use of Trp and its metabolites is optional based on their antioxidant properties during pregnancy. Second, dynamic Trp metabolism is an accommodation mechanism in response to OS. Third, regulation of Trp metabolism could be used to control/attenuate OS according to variations in Trp metabolism during pregnancy. Fourth, OS-mediated injury could be alleviated by regulation of Trp metabolism in pregnancy-associated disorders. Future studies in normal/abnormal pregnancies and in associated disorders should include measurements of free Trp, total Trp, Trp metabolites, and activities of Trp-degrading enzymes in plasma. Abnormal pregnancies and some associated disorders may be associated with disordered Trp metabolism related to OS. Mounting evidence suggests that the investigation of the use of Trp and its metabolites in pregnancy will be meanful.

MRI radiomics-based interpretable model and nomogram for preoperative prediction of Ki-67 expression status in primary central nervous system lymphoma.

Objectives: To investigate the value of interpretable machine learning model and nomogram based on clinical factors, MRI imaging features, and radiomic features to predict Ki-67 expression in primary central nervous system lymphomas (PCNSL). Materials and methods: MRI images and clinical information of 92 PCNSL patients were retrospectively collected, which were divided into 53 cases in the training set and 39 cases in the external validation set according to different medical centers. A 3D brain tumor segmentation model was trained based on nnU-NetV2, and two prediction models, interpretable Random Forest (RF) incorporating the SHapley Additive exPlanations (SHAP) method and nomogram based on multivariate logistic regression, were proposed for the task of Ki-67 expression status prediction. Results: The mean dice Similarity Coefficient (DSC) score of the 3D segmentation model on the validation set was 0.85. On the Ki-67 expression prediction task, the AUC of the interpretable RF model on the validation set was 0.84 (95% CI:0.81, 0.86; p < 0.001), which was a 3% improvement compared to the AUC of the nomogram. The Delong test showed that the z statistic for the difference between the two models was 1.901, corresponding to a p value of 0.057. In addition, SHAP analysis showed that the Rad-Score made a significant contribution to the model decision. Conclusion: In this study, we developed a 3D brain tumor segmentation model and used an interpretable machine learning model and nomogram for preoperative prediction of Ki-67 expression status in PCNSL patients, which improved the prediction of this medical task. Clinical relevance statement: Ki-67 represents the degree of active cell proliferation and is an important prognostic parameter associated with clinical outcomes. Non-invasive and accurate prediction of Ki-67 expression level preoperatively plays an important role in targeting treatment selection and patient stratification management for PCNSL thereby improving prognosis.

Impacts of obesity on global subclinical left cardiac function represented by CMR-derived myocardial strain, TyG index may be a predictor.

Obesity is a recognized risk factor for heart failure. People with similar weights may have different metabolic health. Notably, insulin resistance is a hallmark of obesity and a feature of heart failure. We aimed to evaluate the effects of obesity and metabolic health status on subclinical left cardiac function. We also investigated whether insulin resistance (TyG index) plays a role in BMI-linked subclinical left cardiac dysfunction. The study involved 403 volunteers. Hierarchical multiple regression models were used to assess associations between obesity, metabolic health, and overall subclinical left cardiac function. Mediating analysis was used to explore the role of the TyG index in the association between BMI and left cardiac function. Finally, ROC analysis was performed to explore the predictive value of the TyG index in subclinical left cardiac dysfunction. The correlation analysis showed that metabolic unhealth increased the risk of subclinical left ventricular (LV) dysfunction; obesity was associated with an increased risk of global left cardiac dysfunction regardless of metabolic health status. The TyG index mediated 25% of the associations between BMI and Left atrial (LA) functional parameters. ROC analysis exhibited that the TyG index can be used as a predictor of LA dysfunction (AUC = 0.63), and the optimal cut-off point for the TyG index is 9.33. Even a "non-obese metabolically unhealthy" is a detrimental state of early LV function; obesity remains a major risk factor for global subclinical left cardiac dysfunction. Using the TyG index could allow early identification of individuals at high risk of subclinical left cardiac dysfunction.Registration number: ChiCTR2200057991; Date of registration: 2022-03-25. URL: http://www.chictr.org.cn/showproj.aspx?proj=162316 .

Cellulose based composite sponges with oriented porous structure and superabsorptive capacity for quick hemostasis.

Excessive bleeding is the leading cause of death in accidents and operations. Ca2+ crosslinked carboxyl nanocellulose (CN)/montmorillonite (MMT) composite (CaCNMMT) sponges were prepared by uniform mixing and directional freeze-drying methods which was inspired by the coordination mechanism of blood clot formation and coagulation cascade activation in natural hemostasis process. Carboxyl nanocellulose (CaCN) sponge has instantaneous water absorption capacity, and CaCNMMT sponges could further activate clotting factors. Therefore, CaCNMMT sponges achieved quick hemostasis by efficient concentrating blood, inducing hemocyte aggregation and stimulating coagulation cascade activation based on the synergistic effects of CN and MMT. Blood clotting index of CaCNMMT (15.90 ± 0.52 %) was significantly lower than CaCN (59.3 ± 1.43 %), and APTT time (22 ± 2 s) was almost equivalent to MMT (20 ± 2 s). CaCNMMT sponge showed good quick hemostatic effect on massive hemorrhage in both tail-breaking and liver injury model which provided a new strategy for the application of MMT in hemostatic and trauma treatment fields.

Peppermint extract improves egg production and quality, increases antioxidant capacity, and alters cecal microbiota in late-phase laying hens.

Introduction: Peppermint contains substantial bioactive ingredients belonging to the phytoestrogens, and its effects on the production of late-laying hens deserve more attention. This study evaluated the effects of dietary peppermint extract (PE) supplementation on egg production and quality, yolk fatty acid composition, antioxidant capacity, and cecal microbiota in late-phase laying hens. Method: PE powder was identified by UPLC-MS/MS analysis. Two hundred and sixteen laying hens (60 weeks old) were randomly assigned to four treatments, each for 28 days: (i) basal diet (control group, CON); (ii) basal diet + 0.1% PE; (iii) basal diet + 0.2% PE; and (iv) basal diet + 0.4% PE. Egg, serum, and cecal samples were collected for analysis. Results: Dietary PE supplementation increased the laying rate, serum triglyceride, immunoglobulin G, and total antioxidant capacity, while 0.2 and 0.4% PE supplementation increased eggshell thickness, serum total protein level, and superoxide dismutase activity of laying hens compared with the CON group (P < 0.05). PE addition in diets increased the C14:0, C18:3n3, C18:3n6, C23:0, C24:0, and C24:1n9 contents in the yolk. In addition, the egg yolk saturated fatty acid content was higher (P < 0.05) in the 0.2 and 0.4% PE groups compared with the CON and 0.1% PE groups. The microbiota analysis revealed that the cecal phylum Proteobacteria was decreased (P < 0.05) in the PE-supplemented groups. A total of 0.4% PE supplementation increased the cecal richness of gram-positive bacteria and decreased the richness of gram-negative and potentially pathogenic bacteria compared with the 0.1% PE group (P < 0.05). Microbial function prediction analysis showed that the cecal microbiota of the PE group was mainly enriched by fatty acid degradation, fatty acid metabolism, amino sugar metabolism, nucleotide sugar metabolism, and other pathways. Regression analysis suggested that 0.28-0.36% PE supplementation was the optimal level for improving egg production and quality, antioxidant capacity, and yolk fatty acid in late-phase laying hens. Discussion: Dietary PE supplementation improved egg production and quality (including yolk fatty acid composition) by increasing serum IgG and antioxidant capacity and modulating the intestinal microbiota in late-phase laying hens.

Ligature induced periodontitis in rats causes gut dysbiosis leading to hepatic injury through SCD1/AMPK signalling pathway.

AIMS: Previous studies have demonstrated that chronic periodontitis (CP) is closely associated with the occurrence and development of a variety of systemic diseases. In this study, we successfully constructed a rat CP model through dental silk ligation, and the corresponding inflammatory reactions and fatty lesions were observed in the liver. MAIN METHODS: Sprague-Dawley rats (n = 6) underwent tooth ligation at the bilateral first molars with silk thread to induce CP and were sacrificed 8 weeks later and compared to non-ligated rats (n = 6). RNA sequencing and 16S rRNA analysis were performed to determine the molecular mechanisms of CP involved in inducing liver disease. Alveolar bone loss, liver enzymes, mandible and liver histopathology, and inflammatory responses were compared between groups. KEY FINDINGS: RNA sequencing of liver tissue showed that the expression of SCD1 increased significantly in CP rats compared to controls. KEGG enrichment analysis showed that the AMPK signalling pathway may be involved in liver steatosis. The intestinal flora of faecal samples of rats were analysed by 16S rRNA sequencing, and the results indicated that the intestinal flora of the CP group was evidently imbalanced. The expression levels of tight junction proteins (ZO-1, occludin, and claudin-1) were significantly reduced in CP rats. Meanwhile, increases in serum IL-1ß and lipopolysaccharide in CP rats reflected a systemic inflammatory response. SIGNIFICANCE: CP may be involved in the occurrence and development of hepatic injury and liver steatosis, and its mechanism may be related to the oral-gut-liver axis and SCD1/AMPK signal activation in the liver.

Modulating Effect of Paeonol on Piglets With Ulcerative Colitis.

Piglet enteritis is a major problem that needs to be solved urgently in modern pig production. Paeonol (Pae) has been used as a novel treatment option due to its good medicinal value. This study purported to elucidate the regulatory mechanism of Pae on dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) in weaned piglets. A total of 36 crossbred (Duroc × Landrace × Yorkshire) weaned piglets were stochastically split into six groups: the control group, DSS group, 0.2% Pae group, 0.4% Pae group, 0.8% Pae group, and mesalazine group. The control and DSS groups were fed with a basic diet, the three Pae and mesalazine groups were fed with 0.2, 0.4, 0.8%, and 2 g mesalazine per kilogram of basic diet throughout the study. On the 15th day of the test period, the control group was gavaged with 10 ml of normal saline, while the remaining five groups were gavaged with 10 ml 5% DSS solution for 13 days. The study lasted for 27 days. The results showed that the 0.8% Pae group significantly increased the average daily feed intake (ADFI) and Occludin mRNA expression in the colon of piglets (P < 0.05). The 0.2% Pae group markedly increased the average daily gain (ADG) and zonula occludens-1 (ZO-1) mRNA expression (P < 0.05). In the 0.2% and 0.4% Pae groups, the feed-to-gain ratio (F/G) was significantly reduced and the mRNA expression levels of Caspase-8, respectively, markedly enhanced the mRNA expression levels of transforming growth factor-ß (TGF-ß) and interleukins-4 (IL-4) (P < 0.05). In the 0.8% Pae group, the relative abundance of Campilobacterota was significantly reduced (P < 0.05). In the 0.4% Pae group, the relative abundance of Firmicutes was notably increased (P < 0.05). In the 0.2 and 0.8% Pae groups, the relative abundance of Prevotella was markedly increased (P < 0.05). In the 0.2% Pae group, the contents of propionic acid, butyric acid, and valerate acid were markedly higher (P < 0.05). Thus, it is speculated that Pae may regulate the balance of anti-inflammatory/pro-inflammatory factors, improve intestinal tight junction expression, reduce apoptosis, and improve intestinal microflora structure and growth performance of piglets, thereby restoring intestinal barrier function and alleviating DSS-induced UC in piglets.

L-Tryptophan activates the aryl hydrocarbon receptor and induces cell cycle arrest in porcine trophectoderm cells.

During implantation, the proliferation of trophectoderm cells (the outer epithelium of blastocysts) is related to conceptus elongation and placenta formation. Tryptophan (Trp) is a key regulator of embryogenesis and embryonic implantation during pregnancy. We sought to determine whether different concentrations of Trp alters porcine trophectoderm (pTr) cell proliferation. pTr cells were cultured in medium containing 40, 500, or 1000 µM Trp. The cell proliferation rate and the progression of the cells through the cell cycle were determined. To identify differentially expressed genes (DEGs) in the pTr cells, we compared mRNA transcriptomes by RNA-Seq after cell treatment with different concentrations of Trp. Some candidate DEGs were identified by quantitative reverse transcription PCR (qPCR). High L-Trp levels (500 and 1000 µM) inhibited cell proliferation and induced cell cycle arrest. We identified 19 DEGs between the 500 µM L-Trp and 40 µM L-Trp groups and 168 DEGs between the 1000 µM L-Trp and 40 µM L-Trp groups and subsequently used qPCR to validate some genes that were upregulated or downregulated. The functional gene networks in which the DEGs were most enriched included those associated with regulating DNA replication and the cell cycle, and the majority of the DEGs in both of these functional pathways was downregulated. The results showed that the addition of 500 and 1000 µM Trp significantly increased the abundance of proteins in the Aryl Hydrocarbon Receptor (AHR) signaling pathway. Collectively, these results indicate a novel and important role for Trp in mediating the proliferation of porcine placental cells largely via the AHR signaling pathway. Additionally, these findings help to explain the side effects of excessive Trp supplementation on placenta development and embryo growth in mammals.

Effects of Coated Cysteamine on Oxidative Stress and Inflammation in Weaned Pigs.

This study aimed to explore the effects of dietary coated cysteamine on oxidative stress and inflammation in diquat-induced weaning pigs. Twenty-four pigs were randomly assigned to three dietary groups with eight replicates: the control (fed base diet), diquat (fed base diet), and coated cysteamine + diquat groups (fed 80 mg/kg cysteamine). The experiment was conducted for 21 d, and consisted of a pre-starter period (14 d) and a starter period (7 d). Coated cysteamine treatment significantly increased (p < 0.05) the final weight and average daily gain (ADG) in pigs. The contents of alkaline phosphatase (ALP), immunoglobulin G (IgG), serine (Ser), and isoleucine (Ile) were elevated (p < 0.05) while the contents of albumin (ALB) and aspartic acid (Asp) were reduced (p < 0.05) in the serum after coated cysteamine supplementation. Coated cysteamine supplementation resulted in greater (p < 0.05) serum superoxide dismutase (SOD) activity, the expression of interleukin-10 (IL-10) mRNA in the colon, and the CuSOD mRNA expression in the jejunum (p < 0.05) and colon (p = 0.073). Coated cysteamine supplementation showed an increasing trend in villus height (p = 0.060), villus height/crypt depth (V/C) (p = 0.056), the expression levels of zonula occludens-1 (ZO-1) mRNA (p = 0.061), and Occludin mRNA (p = 0.074) in the jejunum. In summary, dietary supplementation with coated cysteamine improves the intestinal barrier function of the jejunum by increasing the immunoglobulin content and the relative expression of intestinal immune factor mRNA in pigs while alleviating oxidative stress and inflammatory reactions caused by diquat.

Adaptive T cell immunotherapy in cancer.

Impaired tumor-specific effector T cells contribute to tumor progression and unfavorable clinical outcomes. As a compensatory T cell-dependent cancer immunoediting strategy, adoptive T cell therapy (ACT) has achieved encouraging therapeutic results, and this strategy is now on the center stage of cancer treatment and research. ACT involves the ex vivo stimulation and expansion of tumor-infiltrating lymphocytes (TILs) with inherent tumor reactivity or T cells that have been genetically modified to express the cognate chimeric antigen receptor or T cell receptor (CAR/TCR), followed by the passive transfer of these cells into a lymphodepleted host. Primed T cells must provide highly efficient and long-lasting immune defense against transformed cells during ACT. Anin-depth understanding of the basic mechanisms of these living drugs can help us improve upon current strategies and design better next-generation T cell-based immunotherapies. From this perspective, we provide an overview of current developments in different ACT strategies, with a focus on frontier clinical trials that offer a proof of principle. Meanwhile, insights into the determinants of ACT are discussed, which will lead to more rational, potent and widespread applications in the future.

Dietary Moutan Cortex Radicis Improves Serum Antioxidant Capacity and Intestinal Immunity and Alters Colonic Microbiota in Weaned Piglets.

Background: Moutan cortex radicis (MCR), as a common traditional Chinese medicine, has been widely used as an antipyretic, antiseptic, and anti-inflammatory agent in China. Objectives: This study aimed to investigate the effects of dietary MCR supplementation on the antioxidant capacity and intestinal health of the pigs and to explore whether MCR exerts positive effects on intestinal health via regulating nuclear factor kappa-B (NF-κB) signaling pathway and intestinal microbiota. Methods: MCR powder was identified by LC-MS analysis. Selected 32 weaned piglets (21 d of age, 6.37 ± 0.10 kg average BW) were assigned (8 pens/diet, 1 pig/pen) to 4 groups and fed with a corn-soybean basal diet supplemented with 0, 2,000, 4,000, and 8,000 mg/kg MCR for 21 d. After the piglets were sacrificed, antioxidant indices, histomorphology examination, and inflammatory signaling pathway expression were assessed. The 16s RNA sequencing was used to analyze the effects of MCR on the intestinal microbiota structure of piglets. Results: Supplemental 4,000 mg/kg MCR significantly increased (P < 0.05) the average daily weight gain (ADG), average daily feed intake (ADFI), total antioxidative capability, colonic short-chain fatty acids (SCFA) concentrations, and the crypt depth in the jejunum but decreased (P < 0.05) the mRNA expression levels of interferon γ, tumor necrosis factor-α, interleukin-1ß, inhibiting kappa-B kinase ß (IKKß), inhibiting nuclear factor kappa-B (IκBα), and NF-κB in the jejunum and ileum. Microbiota sequencing identified that MCR supplementation significantly increased the microbial richness indices (Chao1, ACE, and observed species, P < 0.05) and the relative abundances of Firmicutes and Lactobacillus (P < 0.05), decreased the relative abundances of Bacteroides, Parabacteroides, unidentified_Lachnospiraceae, and Enterococcus (P < 0.05) and had no significant effects on the diversity indices (Shannon and Simpson, P > 0.05). Microbial metabolic phenotypes analysis also showed that the richness of aerobic bacteria and facultative anaerobic bacteria, oxidative stress tolerance, and biofilm forming were significantly increased (P < 0.05), and the richness of anaerobic bacteria and pathogenic potential of gut microbiota were reduced (P < 0.05) by MCR treatment. Regression analysis showed that the optimal MCR supplemental level for growth performance, serum antioxidant capacity, and intestinal health of weaned piglets was 3,420 ~ 4,237 mg/kg. Conclusions: MCR supplementation improved growth performance and serum antioxidant capacity, and alleviated intestinal inflammation by inhibiting the IKKß/IκBα/NF-κB signaling pathway and affecting intestinal microbiota in weaned piglets.

Imbalanced dietary methionine-to-sulfur amino acid ratio can affect amino acid profiles, antioxidant capacity, and intestinal morphology of piglets.

Animal protein sources such as fishmeal and plasma powder are excellent and indispensable sources of energy, amino acids, and minerals in animal production. Amino acid imbalance, especially methionine-to-sulfur amino acid (Met:SAA) ratio, caused by an imbalance of animal protein meal leads to growth restriction. This study was conducted to evaluate the effects of imbalanced Met:SAA ratio supplementation of different animal protein source diets on growth performance, plasma amino acid profiles, antioxidant capacity and intestinal morphology in a piglet model. Twenty-four weaned piglets (castrated males; BW = 10.46 ± 0.34 kg), assigned randomly into 3 groups (8 piglets/group), were fed for 28 d. Three experimental diets of equal energy and crude protein levels were as follows: 1) a corn-soybean basal diet with a Met:SAA ratio at 0.51 (BD); 2) a plasma powder diet with a low Met:SAA ratio at 0.41 (L-MR); 3) a fishmeal diet with a high Met:SAA ratio at 0.61 (H-MR). Results revealed that compared to BD, L-MR significantly decreased (P < 0.05) the activities of plasma total antioxidant capacity and glutathione peroxidase, plasma amino acid profiles, and significantly reduced (P < 0.05) villus height and crypt depth in the duodenum and jejunum. Additionally, L-MR significantly reduced (P < 0.05) the mRNA expression level of solute carrier family 7 member 9 (SlC7A9) in the ileum, and significantly increased (P < 0.05) mRNA expression levels of zonula occludens-1 (ZO-1) in the duodenum, and Claudin-1, ZO-1, sodium-coupled neutral amino acid transporters 2 (SNAT2) and SlC7A7 in the jejunum. H-MR significantly increased (P < 0.05) plasma SAA levels, and significantly reduced (P < 0.05) average daily feed intake, villus height, and villus height-to-crypt depth (VH:CD) ratio in the ileum compared to BD. In conclusion, L-MR may result in oxidative stress and villous atrophy but proves beneficial in improving intestinal barrier function and the activity of amino acid transporters for compensatory growth. H-MR may impair intestinal growth and development for weaned piglets. The research provides a guidance on the adequate Met:SAA ratio (0.51) supplementation in diet structure for weaned piglets.