Nutritional induction of endogenous antimicrobial peptide expression is considered a promising approach to inhibit the outgrowth and infection of pathogenic microbes in mammals. The present study investigated possible regulation of porcine epithelial β-defensins in response to branched-chain amino acids (BCAA) in vivo and in vitro. BCAA treatment increased relative mRNA expression of jejunal and ileal β-defensins in weaned piglets. In IPEC-J2 cells, isoleucine, leucine, and valine could stimulate β-defensin expression, possibly associated with stimulation of ERK1/2 phosphorylation. Inhibition of Sirt1 and ERK completely blocked the activation of ERK and 90RSK protein by isoleucine, simultaneously decreasing defensin expression. BCAA stimulate expression of porcine intestinal epithelial β-defensins with isoleucine the most, potent possibly through activation of the Sirt1/ERK/90RSK signaling pathway. The β-defensins regulation of lipopolysaccharide was related with an ERK-independent pathway. BCAA modulation of endogenous defensin might be a promising approach to enhance disease resistance and intestinal health in young animals and children.

Investigation of targeting inhibitors of Aβ aggregation, heme-Aβ peroxidase-like activity and efficient detectors of Aβ aggregation, are of therapeutic value and diagnostics significance for the treatment of Alzheimer's disease (AD). Due to the complex pathogenesis of AD, theranostics treatment with multiple functions are necessary. Herein we constructed the NIR absorption property of gold nanorods (GNRs) loaded with single chain variable fragment ( scFv ) 12B4 and thermophilic acylpeptide hydrolase (APH) ST0779 as a smart theranostic complex (GNRs-APH- scFv , GAS), which possesses both rapid detection of Aβ aggregates and NIR photothermal treatment that effectively disassembles Aβ aggregates and inhibits Aβ-mediated toxicity. Methods : We screened targeting anti-Aβ scFv 12B4 and thermophilic acylpeptide hydrolase as amyloid-degrading enzyme, synthesized GAS gold nanorods complex. The GAS was evalued by Aβ inhibition and disaggregation assays, Aβ detection assays, Aβ mediated toxicity assays in vitro . In vivo, delaying Aβ-induced paralysis in AD model of Caenorhabditis elegans was also tested by GAS. Results : In vitro , GAS has a synergistic effect to inhibit and disassociate Aβ aggregates, in addition to decrease heme-Aβ peroxidase-like activity. In cultured cells, treatment with GAS reduces Aβ-induced cytotoxicity, while also delaying Aβ-mediated paralysis in CL4176 C.elegans model of AD. Furthermore, the photothermal effect of the GAS upon NIR laser irradiation not only helps disassociate the Aβ aggregates but also boosts APH activity to clear Aβ. The GAS, as a targeting detector and inhibitor, allows real-time detection of Aβ aggregates. Conclusion : These results firstly highlight the combination of scFv , APH and nanoparticles to be theranostic AD drugs. Taken together, our strategy provides a new thought into the design of smart compounds for use as efficiently therapeutic and preventive agents against AD. Moreover, our design provides broad prospects of biomedical strategy for further theranostics application in those diseases caused by abnormal protein.

The objective of this study was to investigate whether valine (Val) supplementation in a reduced protein (RP) diet regulates growth performance associated with the changes in plasma amino acids (AAs) profile, metabolism, endocrine, and neural system in piglets. Piglets or piglets with a catheter in the precaval vein were randomly assigned to two treatments, including two RP diets with standardized ileal digestible (SID) Val:Lysine (Lys) ratio of 0.45 and 0.65, respectively. The results indicated that piglets in the higher Val:Lys ratio treatment had higher average daily feed intake (ADFI) ( P < 0.001), average daily gain (ADG) ( P = 0.001), feed conversion ratio (FCR) ( P = 0.004), lower plasma urea nitrogen ( P = 0.032), expression of gastric cholecystokinin (CCK), and hypothalamic pro-opiomelanocortin (POMC). Plasma AAs profiles including postprandial plasma essential AAs (EAAs) profile and in serum, muscle, and liver involved in metabolism of AAs and fatty acids were significantly different between two treatments. In conclusion, Val influenced growth performance associated with metabolism of AAs and fatty acids and both endocrine and neural system in piglets.

Spatial outliers are the spatial objects whose nonspatial attribute values are quite different from those of their spatial neighbors. Identification of spatial outliers is an important task for data mining researchers and geographers. A number of algorithms have been developed to detect spatial anomalies in meteorological images, transportation systems, and contagious disease data. In this paper, we propose a set of graph-based algorithms to identify spatial outliers. Our method first constructs a graph based on k-nearest neighbor relationship in spatial domain, assigns the differences of nonspatial attribute as edge weights, and continuously cuts high-weight edges to identify isolated points or regions that are much dissimilar to their neighboring objects. The proposed algorithms have three major advantages compared with other existing spatial outlier detection methods: accurate in detecting both point and region outliers, capable of avoiding false outliers, and capable of computing the local outlierness of an object within subgraphs. We present time complexity of the algorithms, and show experiments conducted on US housing and Census data to demonstrate the effectiveness of the proposed approaches.

Background: Chronic inflammation is a pathophysiological cause of sarcopenia in Crohn’s disease (CD) patients. However, the potential impact of diet-related inflammation on sarcopenia has not yet been adequately investigated. We examined the associations between Dietary Inflammatory Index (DII) and sarcopenia in CD patients. Methods: A total of 140 CD patients from Ruijin Hospital in Shanghai were included in this cross-sectional study. DII scores were calculated from the dietary data collected using a validated food frequency questionnaire (FFQ). Sarcopenia was determined according to the Asian Working Group for Sarcopenia. Multivariable logistic regression analyses were performed to determine the association between DII and sarcopenia. Results: The mean DII score was 0.81 ± 2.13, ranging from −3.24 to 4.89. The overall prevalence of sarcopenia was 26.4%. The higher DII score significantly increased the risk of sarcopenia in CD patients (ORQuartile4vs1: 9.59, 95% CI: 1.69, 54.42, ptrend = 0.031) in the multivariable model after adjusting for more potential confounders. Moreover, CD patients with a higher DII had a significantly higher appendicular skeletal muscle mass index (ASMI, ORQuartile4vs1: 5.48, 95% CI: 1.51, 19.87, ptrend = 0.018) after adjusting for age, gender, BMI, smoking status and drinking status model. Yet, there were no significant differences between DII and ASMI after adjusting for more potential confounders. Additionally, no significant association was observed between DII and handgrip strength in the multivariable-adjusted models. Conclusions: Pro-inflammatory diet was associated with increased risk of sarcopenia in CD patients. CD patients should have a proper intake of energy and protein. These patients could also benefit from supplementation with enteral nutrition due to its anti-inflammatory potential.