Prediction of Anti-rheumatoid Arthritis Natural Products of Xanthocerais Lignum Based on LC-MS and Artificial Intelligence.

AIMS: Employing the technique of liquid chromatography-mass spectrometry (LCMS) in conjunction with artificial intelligence (AI) technology to predict and screen for antirheumatoid arthritis (RA) active compounds in Xanthocerais lignum. BACKGROUND: Natural products have become an important source of new drug discovery. RA is a chronic autoimmune disease characterized by joint inflammation and systemic inflammation. Although there are many drugs available for the treatment of RA, they still have many side effects and limitations. Therefore, finding more effective and safer natural products for the treatment of RA has become an important issue. METHODS: In this study, a collection of inhibitors targeting RA-related specific targets was gathered. Machine learning models and deep learning models were constructed using these inhibitors. The performance of the models was evaluated using a test set and ten-fold cross-validation, and the most optimal model was selected for integration. A total of five commonly used machine learning algorithms (logistic regression, k-nearest neighbors, support vector machines, random forest, XGBoost) and one deep learning algorithm (GCN) were employed in this research. Subsequently, a Xanthocerais lignum compound library was established through HPLC-Q-Exactive- MS analysis and relevant literature. The integrated model was utilized to predict and screen for anti-RA active compounds in Xanthocerais lignum. RESULTS: The integrated model exhibited an AUC greater than 0.94 for all target datasets, demonstrating improved stability and accuracy compared to individual models. This enhancement enables better activity prediction for unknown compounds. By employing the integrated model, the activity of 69 identified compounds in Xanthocerais lignum was predicted. The results indicated that isorhamnetin-3-O-glucoside, myricetin, rutinum, cinnamtannin B1, and dihydromyricetin exhibited inhibitory effects on multiple targets. Furthermore, myricetin and dihydromyricetin were found to have relatively higher relative abundances in Xanthocerais lignum, suggesting that they may serve as the primary active components contributing to its anti-RA effects. CONCLUSION: In this study, we utilized AI technology to learn from a large number of compounds and predict the activity of natural products from Xanthocerais lignum on specific targets. By combining AI technology and the LC-MS approach, rapid screening and prediction of the activity of natural products based on specific targets can be achieved, significantly enhancing the efficiency of discovering new bioactive molecules from medicinal plants.

Regional ventilation distribution before and after laparoscopic lung parenchymal resection.

Objective.The aim of the present study was to evaluate the influence of one-sided pulmonary nodule and tumour on ventilation distribution pre- and post- partial lung resection.Approach.A total of 40 consecutive patients scheduled for laparoscopic lung parenchymal resection were included. Ventilation distribution was measured with electrical impedance tomography (EIT) in supine and surgery lateral positions 72 h before surgery (T1) and 48 h after extubation (T2). Left lung to global ventilation ratio (Fl), the global inhomogeneity index (GI), standard deviation of regional ventilation delay (RVDSD) and pendelluft amplitude (Apendelluft) were calculated to assess the spatial and temporal ventilation distribution.Main results.After surgery (T2), ventilation at the operated chest sides generally deteriorated compared to T1 as expected. For right-side resection, the differences were significant at both supine and left lateral positions (p< 0.001). The change of RVDSDwas in general more heterogeneous. For left-side resection, RVDSDwas worse at T2 compared to T1 at left lateral position (p= 0.002). The other EIT-based parameters showed no significant differences between the two time points. No significant differences were observed between supine and lateral positions for the same time points respectively.Significance.In the present study, we found that the surgery side influenced the ventilation distribution. When the resection was performed on the right lung, the postoperative ipsilateral ventilation was reduced and the right lung ratio fell significantly. When the resection was on the left lung, the ventilation delay was significantly increased.

Synthesis, anti-inflammatory activity, and conformational relationship studies of chromone derivatives incorporating amide groups.

Inflammation is the initial biological reaction of the immune system to various stimuli such as infection, injury, or irritation. Extensive research has demonstrated that a growing array of diseases are triggered by inflammatory mechanisms. Currently, anti-inflammatory drugs are widely utilized in clinical practice due to their therapeutic advantages; however, the potential side effects cannot be ignored by us. In our work, a series of amide compounds with chromones as the parent nucleus were designed and synthesized using the principle of colligated drug design. The results of the biological evaluation indicated that four compounds exhibited lower EC50 values compared to the positive drug ibuprofen. Notably, compound 5-9 showed optimal inhibitory activity (EC50 = 5.33 ± 0.57 µM) against the production of nitric oxide (NO) induced by lipopolysaccharide (LPS) in RAW264.7 cells. Structure-activity relationships (SAR) showed that the presence of electron-withdrawing groups at positions 5 and 8, or electron-donating groups at positions 6 and 7 of the parent nucleus of the chromones can enhance the anti-inflammatory activity of the chromones. The molecular docking studies predicted the mode of interaction between the compounds and protein. Additionally, these studies have demonstrated that the amide bond is the key radical to the anti-inflammatory effect. Based on the summary of the aforementioned studies, it can be inferred that compound 5-9 exhibit potential as an anti-inflammatory drug that deserves further investigation.

Dexmedetomidine Improves Anxiety-like Behaviors in Sleep-Deprived Mice by Inhibiting the p38/MSK1/NFκB Pathway and Reducing Inflammation and Oxidative Stress.

(1) Background: Sleep deprivation (SD) triggers a range of neuroinflammatory responses. Dexmedetomidine can improve sleep deprivation-induced anxiety by reducing neuroinflammatory response but the mechanism is unclear; (2) Methods: The sleep deprivation model was established by using an interference rod device. An open field test and an elevated plus maze test were used to detect the emotional behavior of mice. Mouse cortical tissues were subjected to RNA sequence (RNA-seq) analysis. Western blotting and immunofluorescence were used to detect the expression of p38/p-p38, MSK1/p-MSK1, and NFκBp65/p- NFκBp65. Inflammatory cytokines were detected using enzyme-linked immunosorbent assay (ELISA); (3) Results: SD triggered anxiety-like behaviors in mice and was closely associated with inflammatory responses and the MAPK pathway (as demonstrated by transcriptome analysis). SD led to increased expression levels of p-p38, p-MSK1, and p-NFκB. P38 inhibitor SB203580 was used to confirm the important role of the p38/MSK1/NFκB pathway in SD-induced neuroinflammation. Dexmedetomidine (Dex) effectively improves emotional behavior in sleep-deprived mice by attenuating SD-induced inflammatory responses and oxidative stress in the cerebral cortex, mainly by inhibiting the activation of the p38/MSK1/NFκB pathway; (4) Conclusions: Dex inhibits the activation of the p38/MSK1/NFκB pathway, thus attenuating SD-induced inflammatory responses and oxidative stress in the cerebral cortex of mice.

Tibial fracture surgery in elderly mice caused postoperative neurocognitive disorder via SOX2OT lncRNA in the hippocampus.

Increasing evidence indicates the major role of mitochondrial function in neurodegenerative disease. However, it is unclear whether mitochondrial dynamics directly affect postoperative neurocognitive disorder (PND). This study aimed to analyze the underlying mechanisms of mitochondrial dynamics in the pathogenesis of PND. Tibial fracture surgery was performed in elderly mice to generate a PND model in vivo. Cognitive behavior was evaluated 3 days post-surgery using novel object recognition and fear conditioning. A gradual increase in the SOX2OT mRNA level and decrease in the SOX2 mRNA level were noted, with impaired cognitive function, in the mice 3 days after tibial surgery compared with mice in the sham group. To evaluate the role of SOX2OT in PND, SOX2OT knockdown was performed in vitro and in vivo using lentivirus transfection in HT22 cells and via brain stereotactic injection of lentivirus, respectively. SOX2OT knockdown reduced apoptosis, inhibited oxidative stress, suppressed mitochondrial hyperdivision, attenuated surgery-induced cognitive dysfunction, and promoted downstream SOX2 expression in elderly mice. Furthermore, Sox2 alleviated mitochondrial functional damage by inhibiting the transcription of mitochondrial division protein Drp1. Our study findings indicate that SOX2OT knockout alleviates surgery-induced mitochondrial fission and cognitive function defects by upregulating the expression of Sox2 in mice, resulting in the inhibition of drp1 transcription. Therefore, regulation of the SOX2/Drp1 pathway may be a potential mechanism for the treatment of patients with PND.

Investigating the molecular mechanisms of delirium-like neuropsychiatric disorder induced by electromagnetic pulse based on bioinformatics analysis.

Electromagnetic pulse (EMP), a unique type of electromagnetic radiation, may induce diverse neuropsychiatric disorders, such as irritability, hyperkinesis, retardation of learning and memory. However, the underlying mechanism of EMP exposure on neuronal injury has not been elucidated. Here, we aimed to delineate the regulatory expression networks based on high-throughput sequencing data to explore the possible molecular mechanisms related to EMP-induced delirium-like neuropsychiatric disorder in rats. It's shown that EMP exposure induced anxiety, cognitive decline and short-term memory impairment. The expression profiles of the long noncoding RNAs (lncRNAs) and mRNAs, along with their biological function and regulatory network, were explored in rats after EMP exposure. We identified 41 differentially expressed lncRNAs (DELs) and 266 differentially expressed mRNAs (DEMs) between EMP and sham groups. Sixty-one co-expression relationships between 18 DELs and 56 DEMs were mostly associated with synapse- and metabolic-related pathways. We predicted 51 DEL-miRNA pairs and 290 miRNA-mRNA pairs using the miRanda database to constructed a DEL-miRNA-DEM network. LncRNA AABR07042999.1 and mRNA Tph2, Slc6a4, Dbh and Th were upregulated, and the contents of serotonin, dopamine and norepinephrine were increased in both PFC and HIP after EMP exposure. The current study provided a better understanding of the ceRNA network, which might reveal the pathological mechanism and provide more treatment options for the EMP-induced neurobehavioral disorder.

How do medication errors occur in the nursing communication process? Investigating the relationship between error types and error factors.

BACKGROUND: Human error types and error factors are two important elements of error analysis. Understanding the relationship between them can contribute to new case analyses, the tendency of error occurrence statistics, error factor identification, and prevention of error recurrence. OBJECTIVE: To provide evidence and guidance for the prevention and improvement of medication communication errors by quantitatively exploring the relationship between error types and error factors. METHODS: Data were collected on self-reported errors in the medication administration process by nurses in all departments of three cooperative medical institutions, and an error sheet of specified style was adopted. Error types were determined by the systematic human error reduction and prediction approach method and human cognition processes. Error factors were extracted using the root cause analysis combined with Berlo's communication model, and the relationship between error types and error factors was quantitatively studied using the partial least-squares regression method. RESULTS: After a one-by-one analysis of 303 error cases, the communication errors occurring in the nursing medication process could be explained by six error types and 12 error factors. In addition, 20 correlation patterns between the error types and error factors were quantitatively obtained, and their path coefficient distributions ranged from 0.088 to 0.467. CONCLUSION: The results of this study may provide reference to understand errors and establish countermeasures from the statistics of error occurrence trends, extract error factors related to error types and determine key error factors.

Effects of nursing workload on medication administration errors: A quantitative study.

BACKGROUND: Medication administration errors by nurses form a high proportion of medical errors in medical institutions. Studies have shown that such errors are closely linked to nursing workload. OBJECTIVE: To quantitatively explore the effects of different types of nursing workloads on different medication administration errors. METHOD: Three medical institutions were selected as the objects of error data collection based on the following criteria: the medical institution experience in error data collection, the complete range of medical departments, and the institution size. Error cases were self-reported from all nurses in all medical departments. The relationship between the error types and nursing workload types were quantitatively examined using partial least squares and structural equation modeling. RESULTS: The study recorded 290 medication administration errors, and extracted four error types and nine nursing workload types. The workload type for each error type was also identified and the path coefficient was found to be between 0.087 to 0.416. CONCLUSION: This study confirmed the effect of workload on medication administration errors and determined a theoretical mechanism for this effect. Research results will provide the evidence for nursing managers to reduce workload and ensure quality in the nursing administration process.

The application of proteomics and metabolomics to reveal the molecular mechanism of Nutmeg-5 in ameliorating cardiac fibrosis following myocardial infarction.

BACKGROUND: Nutmeg-5, an ancient and classic formula in traditional Mongolian medicine comprising five kinds of traditional Chinese medicine, is widely used in the treatment of myocardial infarction (MI, called heart "Heyi" disease in Mongolian medicine). Cardiac fibrosis plays a critical role in the development and progression of heart failure after MI. However, the material basis and pharmacological mechanisms of the effect of Nutmeg-5 on cardiac fibrosis after MI remain unclear. OBJECTIVE: The aim of this study was to first explore the potential material basis and molecular mechanism of action of Nutmeg-5 in improving cardiac fibrosis after MI via a multiomics approach. METHODS: The constituents in Nutmeg-5 were identified by ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). High-performance liquid chromatography (HPLC) and gas chromatography (GC)-based fingerprints of Nutmeg-5 were analysed, and characteristic peaks were identified by comparison to standard samples. A rat MI model was created by permanent ligation of the left anterior descending artery. The protective effect of Nutmeg-5 on cardiac fibrosis after MI was evaluated by tissue histology and measurement of the serum biomarkers of myocardial injury. Cardiac fibrosis levels were evaluated by Sirius red staining. Differentially expressed proteins in the myocardium and metabolites in the serum were explored by proteomic and untargeted metabolome analyses, respectively. Pearson correlation analysis was performed to explore the association between serum metabolites and myocardial proteins. RESULTS: A total of 67 constituents were identified in Nutmeg-5 by UPLC-MS/MS. Sixteen components were identified in the fingerprint of Nutmeg-5 by comparison with a standard sample. Six lactones were isolated from Nutmeg-5 and quantified by HPLC and GC. MI was significantly alleviated in Nutmeg-5-treated rats compared to MI rats, as demonstrated by their decreased mortality, improved cardiac function, and attenuated cardiac fibrosis and myocardial injury. A total of 252 significant differential metabolites were identified in plasma between model and Nutmeg-5-treated rats by untargeted metabolome analysis. Among these, 36 critical metabolites were associated with Nutmeg-5 activity. Proteomic analysis identified 338 differentially expressed proteins in the rat myocardium between MI and Nutmeg-5-treated rats, including 204 upregulated and 134 downregulated proteins. Protein set enrichment analysis revealed that Nutmeg-5 treatment significantly inhibited the extracellular matrix (ECM)-receptor interaction pathway, which was activated in the myocardium of MI rats. A significant decrease in collagen and alpha smooth muscle actin expression levels was found in the myocardium of Nutmeg-5-treated rats compared to MI rats. These results illustrated that Nutmeg-5 had a significant protective effect on cardiac fibrosis after MI. A significant correlation was found between the ECM-receptor interaction pathway in the myocardium and critical metabolites in the serum. In addition, there were positive correlations between the levels of critical metabolites and the expression levels of transforming growth factor (TGF)-ß1 and Smad2 in the rat myocardium. CONCLUSIONS: Nutmeg-5 alleviated cardiac fibrosis after MI in rats by inhibiting the myocardial ECM-receptor interaction pathway and TGF-ß1/Smad2 signalling, which was achieved by regulating plasma metabolites.

Case report: Post-thoracoscopy pendelluft monitoring.

Asynchronous alveolar ventilation is called pendelluft, which may induce lung injury in spontaneously breathing patients. We report a case that electrical impedance tomography (EIT) was used to assess the pendelluft in a post-thoracoscopy patient. The pendelluft amplitude was as high as 77.5% of the tidal variation. The average regional time shift was 0.5 s. The patient was instructed to adjust the breathing method, symptomatic treatment was performed, and the symptoms were improved. This is the first case reporting pendelluft in a post-thoracoscopy patient. Our case demonstrated that (1) pendelluft may occur in post-thoracoscopy patients and it effects lung function, and (2) early identification of affected patients and implementation of corresponding treatments could improve patient outcomes.

The Impact of the SARS-COV-2 Pandemic on the Mental Health and Employment Decisions of Medical Students in North China.

Background: The outbreak of severe respiratory syndrome coronavirus 2 (SARS-COV-2) has led to long periods of social isolation for individuals across the world. Although medical students generally have a high prevalence of mental health problems, they have received less attention than other groups concerning the impact of SARS-COV-2. Therefore, the present study investigated the mental health status, risk factors, and protective factors for mental health problems in medical students in North China during the SARS-COV-2 pandemic. Methods: A WeChat-based survey, which included the Depression Anxiety Stress Scale-21 and measures of social demographics, was performed twice. Risk and protective factors were identified by binary logistic regression analysis. Results: A total of 702 effective questionnaires were collected in two separate surveys. In total, 24.55% of medical students were suffering anxiety to different degrees of severity, 13.18% were suffering depression in the first survey, and 3.71% wanted to give up working in primary medical care during the SARS-COV-2 pandemic in the second survey. In contrast, during the SARS-COV-2 pandemic, a risk factor for anxiety and depression was gender which is male, while being knowledgeable about the SARS-COV-2 pandemic and having a lower academic burden were both protective factors. Conclusions: Measures are required to prevent increases in mental health problems in medical students. Our findings suggest that increasing knowledge about the SARS-COV-2 pandemic and reducing academic burden in medical students is extremely important during the SARS-COV-2 pandemic.

0D/3D coupling of g-C3N4 QDs/hierarchical macro-mesoporous CuO-SiO2 for high-efficiency norfloxacin removal in photo-Fenton-like processes.

Photo-Fenton process is an advanced oxidation technology, which is used to eliminate organic pollutants in environmental pollution. In this paper, g-C3N4 quantum dots incorporated hierarchical macro-mesoporous CuO-SiO2 (MM SC-QDs) composite was successfully fabricated by a dual-template method combined with polystyrene sphere (PS) crystal and copolymer F127. With the presence of H2O2, MM SC-QDs exhibited excellent degradation performance against the antibiotic pollutant norfloxacin (NOR) under visible-light assisted heterogeneous Fenton process at neutral condition, which was 27 times higher than that of the Bulk CuO-SiO2. Interconnected macropores, together with abundant mesopores effectively expand specific surface area and improve mass transfer. In addition, the g-C3N4 QDs served as the separation center for photogenerated charges, promoting the separation and migration of the charge carriers. Wherein, the long-lived photogenerated electrons were effectively separated and transferred to the surface of CuO-SiO2, which accelerated the reduction rate of Cu2+ to Cu+, enhancing the photo-Fenton-like catalytic activity. This stable, efficient, and environmentally friendly Cu-based heterogeneous photo-Fenton-like catalyst is expected to become an effective implementation in organic pollution removal. Meanwhile, this paper proves that Cu-based materials can activate H2O2 to generate singlet oxygen (1O2) for the degradation of organic pollutants. The transformation mechanism of 1O2 was clarified, which is helpful to better understand the Fenton-like reaction process of Cu-based materials.

Duration of the flaxseed diet promotes deposition of n-3 fatty acids in the meat and skin of Peking ducks.

BACKGROUND: Polyunsaturated fatty acids (PUFA), particularly n-3, have beneficial effects on human health, and for this reason foodstuffs with increased content of n-3 PUFA are now very common and widely available. DESIGN: This study was conducted to investigate the effect of the duration of a flaxseed diet on Peking duck's growth performance, antioxidant status, gene expression, and fatty acid profile of the meat. A total of 792 12-day-old white Peking ducks were divided into four groups. In the control group, animals were provided with a basal diet. In the three experimental groups, animals were fed a 10% flax seed diet with vitamin E at 13, 23, and 33 days of age for 30, 20, and 10 days, respectively. RESULTS: The growth performance of the ducks decreased with flaxseed diet's duration. Both body weight and body weight gain decreased linearly while Feed conversion ratios (FCR) increased in the group of ducks fed flaxseed compared to control ducks. Serum triglycerides (TG), very low density lipoprotein (VLDL), low density lipoprotein cholesterol (LDL-C), and aspartate aminotransferase (AST) linearly decreased while high density lipoprotein cholesterol (HDL-C) and lipopolysaccharide (LPS) levels increased by feeding flaxseed up to 30 days. The expression of lipin-1 gene (LPIN-1) and fatty acid desaturase 2 (FADS2) linearly increased in ducks fed flaxseed for 30 days. Linolenic acid (n-3) and its long-chain metabolites like eicosatetraenoic acid (ETA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and total n-3 fatty acids (FA) linearly increased while the ratio of n-6 to n-3 was reduced with increased duration of flaxseed supplementation. CONCLUSION: Overall, we found that increasing the duration of flaxseed diet with vitamin E for more than 10 days had a mild adverse effect on duck's growth performance but enrichedits meat with long-chain PUFA and decreased the n-6 to n-3 ratio, providing quality meat for health-conscious consumers. A period of 20 days is good for producing n-3 enriched Peking duck meat and skin.

Astragaloside IV reduces cardiomyocyte apoptosis in a murine model of coxsackievirus B3-induced viral myocarditis.

Apoptosis plays a crucial role in regulating cardiomyopathy and injuries of coxsackievirus B3 (CVB3)-induced viral myocarditis (VM). It has been reported that Astragaloside IV (AST-IV) from Astragalus membranaceus could inhibit apoptosis under a variety of pathological conditions in vivo or in vitro. However, the functional roles of AST-IV in CVB3-induced VM still remain unknown. Here, we found that AST-IV significantly enhanced survival for CVB3-induced mice. AST-IV protected the mice against CVB3-induced virus myocarditis characterized by the increased body weight, decreased serum level of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH), supressed expression of Ifn-γ, Il-6 in heart, enhanced systolic and diastolic function of left ventricle. At the pathological level, AST-IV ameliorated the mice against CVB3-induced myocardial damage and myocardial fibrosis. In vitro, the results from flow cytometry showed that AST-IV significantly suppressed CVB3-induced cardiomyocytes apoptosis, which also were verified in vivo. Moreover, an increased expression of pro-apoptotic genes including FAS, FASL, cleaved caspase-8 and cleaved caspase-3 was found in CVB3-induced cardiomyocytes, while those was inhibited in cardiomyocytes treated with AST-IV. Taken together, the data suggest that AST-IV protected against CVB3-induced myocardial damage and fibrosis, which may partly attribute to supress activation of FAS/FASL signaling pathway.

Conservative Sensor Error Modeling Using a Modified Paired Overbound Method and its Application in Satellite-Based Augmentation Systems.

Conservative sensor error modeling is of great significance in the field of safety-of-life. At present, the overbound method has been widely used in areas such as satellite-based augmentation systems (SBASs) and ground-based augmentation systems (GBASs) that provide integrity service. It can effectively solve the difficulties of non-Gaussian and non-zero mean error modeling and confidence interval estimation of user position error. However, there is still a problem in that the model is too conservative and leads to the lack of availability. In order to further improve the availability of SBASs, an improved paired overbound method is proposed in this paper. Compared with the traditional method, the improved algorithm no longer requires the overbound function to conform to the characteristics of the probability distribution function, so that under the premise of ensuring the integrity of the system, the real error characteristics can be more accurately modeled and measured. The experimental results show that the modified paired overbound method can improve the availability of the system with a probability of about 99%. In view of the fact that conservative error modeling is more sensitive to large deviations, this paper analyzes the robustness of the improved algorithm in the case of abnormal data loss. The maximum deviation under a certain integrity risk is used to illustrate the effectiveness of the improved paired overbound method compared with the original method.

Influence of starch sources and dietary protein levels on intestinal functionality and intestinal mucosal amino acids catabolism in broiler chickens.

BACKGROUND: There is growing interest in carbohydrate and protein nutrition to enhance the efficiency of animal production. Reduced-crude protein diets depress environmental pollution and feeding cost, but the challenge to their adoption is maintaining digestive function and growth performance of birds. The present study was conducted to evaluate the influence of different dietary starch sources and protein levels on intestinal functionality and mucosal amino acid catabolism. METHODS: Six dietary treatments, based on maize and soybean meal, were offered to 360 AA+ male chicks from 6 to 35 d post-hatch as a 3 × 2 factorial array. Either waxy rice or amylose was added to a conventional maize-soy diet to provide three sources of starch with different digestion rates and relatively high and low dietary protein levels. Growth performance, parameters of intestinal functionality and concentrations of free amino acid in the portal circulation were determined. RESULTS: In the grower phase, starch source influenced (P < 0.02) weight gain as diets containing amylose supported significantly higher weight gains than waxy rice. Significant increase of ileal ATP concentrations and Na+/K+-ATPase activity were found in amylose treatment. Also, amylose decreased BrdU positive cell numbers and down-regulated mRNA expression for CASP-3. GOT activity in the ileum was higher (P < 0.01) in birds offered low protein diets and there was a trend (P = 0.057) for waxy rice as a starch source to increase ileal GOT activities. There was a significant influence on the concentration of seventeen amino acids in the portal circulation with tryptophan the one exception. Waxy rice as a starch source generated 13.6% and 22.4% numerically higher concentrations of non-essential amino acids than maize and amylose, respectively. CONCLUSIONS: Amino acid catabolism in the gut mucosa is subject to nutritional regulation. Given that amino acids can be spared from catabolism in the gut mucosa by supplementation of amylose, it follows their post-enteral availability would be improved and intestinal energy would be derived more efficiently from glucose.

Astragalus polysaccharide from Astragalus Melittin ameliorates inflammation via suppressing the activation of TLR-4/NF-κB p65 signal pathway and protects mice from CVB3-induced virus myocarditis.

Inflammation plays a crucial role in regulating cardiomyopathy and injuries of coxsackievirus B3 (CVB3)-induced viral myocarditis (VM). It has been reported that Astragalus polysaccharide (AP) from Astragalus Melittin could inhabit inflammatory gene expression under a variety of pathological conditions. However, the functional roles of AP in CVB3-induced VM still remain unknown. Here, we found that AP significantly enhanced survival for CVB3-induced mice. AP protected the mice against CVB3-induced myocardial injuries characterized by the increased body weight and depressed serum level of creatine kinase-MB (CK-MB), aspartate transaminases (AST) and lactate dehydrogenase (LDH), enhanced left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS). At the pathological level, AP ameliorated the mice against CVB3-induced myocardial damage, dilated cardiomyopathy and chronic myocardial fibrosis. We subsequently found that AP significantly suppressed CVB3-induced expression of inflammation marker (IL-1ß, IL-6, TNF-α, INF-γ and MCP-1) in heart. Furthermore, we confirmed that AP suppressed the CVB3-induced expression of TLR-4 and phosphorylated NF-κB p65 in heart. Taken together, the data suggest that AP protects against CVB3-induced myocardial damage and inflammation, which may partly attribute to the regulation of TLR-4/NF-κB p65 signal pathway, moreover, suppressive effect of AP on CVB3-induced activation of TLR-4/NF-κB p65 signal was TNF-α-independent.

Proteome and microbiota analysis reveals alterations of liver-gut axis under different stocking density of Peking ducks.

This study aimed to determine the impact of stocking density on the liver proteome and cecal microbiota of Peking ducks. A total of 1,200 21-day-old ducks were randomly assigned to 5 stocking density groups of 5, 6, 7, 8 and 9 ducks/m2, with 6 replicates for each group. At 40 days of age, duck serum and pectorals were collected for biochemical tests; liver and cecal contents of ducks were gathered for proteome and microbiota analysis, respectively. Serum MDA increased while pectorals T-AOC reduced linearly with enhancing stocking density. Duck lipid metabolism was altered under different stocking density as well. Serum LDL-C increased linearly with increasing stocking density. Proteome analysis revealed fatty acid biosynthesis proteins such as acyl-CoA synthetase family member 2 and fatty acid oxidation related proteins including acyl-CoA dehydrogenase long chain and acyl-coenzyme A oxidase were enriched in high stocking density group. Additionally, high stocking density increased oxidative response associated proteins such as DDRGK domain containing 1. Furthermore, increasing stocking density diminished proteins of anti-oxidant capacity including regucalcin and catalase. 16S rDNA analysis revealed that higher stocking density was accompanied with decreased microbial diversity, as well as depletion of anti-inflammatory bacterial taxa, including Bacteroidales, Butyricimonas and Alistipe. Besides, reduced bile acid metabolism-associated bacteria such as Ruminococcaceae, Clostridiales and Desulfovibrionaceae were found in the high-density group. Both proteome and 16S rDNA results showed inflammation and chronic liver disease trend in the high-density group, which suggests the involvement of the liver-gut axis in oxidative stress.

CFTR prevents neuronal apoptosis following cerebral ischemia reperfusion via regulating mitochondrial oxidative stress.

The cystic fibrosis transmembrane conductance regulator (CFTR) is linked to cell apoptosis and abundantly expressed in brain tissue. Mitochondrial oxidative stress plays a key role in activating apoptotic pathway following cerebral ischemia reperfusion (IR) injury. Reduced glutathione (GSH) is exclusively synthesized in cytosol but distributed in mitochondria. In the present study, we investigated whether CFTR affected mitochondrial oxidative stress via regulating GSH and thereby protected neurons against apoptosis following cerebral IR. Brains were subjected to global IR by four-vessel occlusion and CFTR activator forskolin (FSK) was used in vivo. CFTR silence was performed in vitro for neurons by RNA interference. We found that FSK suppressed neuronal apoptosis whereas CFTR silence enhanced neuronal apoptosis. FSK prevented the elevations in reactive oxygen species (ROS) and caspase activities while FSK inhibited the reductions in complex I activity and mitochondrial GSH level following IR. FSK decreased mitochondrial oxidative stress partially and preserved mitochondrial function. On the contrary, CFTR silence exaggerated mitochondrial dysfunction. CFTR loss increased hydrogen peroxide (H2O2) level and decreased GSH level in mitochondria. Importantly, we showed that CFTR was located on mitochondrial membrane. GSH transport assay suggested that GSH decrease may be a consequence not a reason for mitochondrial oxidative stress mediated by CFTR disruption. Our results highlight the central role of CFTR in the pathogenesis of cerebral IR injury. CFTR regulates neuronal apoptosis following cerebral IR via mitochondrial oxidative stress-dependent pathway. The mechanism of CFTR-mediated mitochondrial oxidative stress needs further studies. KEY MESSAGES: CFTR activation protects brain tissue against IR-induced apoptosis and oxidative stress. CFTR disruption enhances H2O2-induced neuronal apoptosis and CFTR loss leads to mitochondrial oxidative stress. CFTR regulates IR-induced neuronal apoptosis via mitochondrial oxidative stress. CFTR may be a potential therapeutic target to cerebral IR damage.

Dietary sodium butyrate improves intestinal development and function by modulating the microbial community in broilers.

This study investigated the effects of dietary sodium butyrate (SB) supplementation, provided as a specially coated product, on growth performance, intestinal development, morphological structure and function in broilers. In total, 720 one-day-old Arbor Acres male broilers were randomly allocated into six treatment groups with six replicates each and then fed basal diets (control) supplemented with 0, 200, 400, 800 or 1000 mg/kg of SB or with antibiotics (100 mg/kg aureomycin and 20 mg/kg colistin sulfate). The growth trial lasted for 42 days. No differences (P>0.05) in growth performance were detected between groups during the grower period (1-21 d) or over the total (1-42 d) trial period, whereas the addition of SB improved the intestinal structure by stimulating (P<0.05) goblet cells on jejunal and ileal villi accompanied by a trend towards increased (Pdiets<0.10) ileal villus height. In addition, more inerratic leaf-shaped villi and mucus secretion and significantly fewer erosions were demonstrated by scanning electron microscopy. Apart from decreased (P<0.05) malondialdehyde (MDA) in the ileal mucosa at 21 d of age, supplemental SB at higher doses (800 mg/kg) led to greater (P<0.05) total antioxidant capacity and depressed (P<0.05) MDA concentrations in the jejunal mucosa. Birds fed with 400 mg/kg and 800 mg/kg SB had higher (P<0.05) acetic acid concentrations at 42 d and higher butyric acid at 21 d in the jejunum chyme. Morever, chicks fed SB diet were found to have higher concentrations of butyric acid (P<0.05) in the ileal chyme. SB additions at 400 mg/kg displayed higher Firmicutes and Proteobacteria levels, while a higher (P<0.05) relative abundance of Bacteroidetes was observed at 800 mg/kg. Furthermore, we found a striking decrease in Enterobacteriaceae and increases in Lachnospiraceae and Rikenellaceae in the cecal lumen of birds fed 800 mg/kg SB as well as a higher proportion of Ruminococcaceae and a noticeable reduction (P<0.05) of Lactobacillaceae in birds treated with 400 mg/kg SB. Taken together, our results support the importance of SB in improving the intestinal development, morphological structure and biological functions of broilers through modulation of the microbial community, which seems to be optimized for gut health at higher doses (800 mg/kg) of SB.