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Our knowledge about the complexity of human milk, in particular fatty acid, protein, and oligosaccharide profiles, has increased considerably in recent years. However, little attention has been paid to nucleotides, which account for ∼2% to 5% of the nonprotein nitrogen fraction of breast milk and provide important cellular and metabolism functions for the infant. We examined literature published in the past 25 years to provide an updated review of concentrations of nucleotides in breast milk across lactational stages in mothers around the world. The free mononucleotides found in highest concentrations in breast milk are, from highest to lowest in the order of cytidine 5'-monophosphate, uridine 5'-monophosphate, and adenosine 5'-monophosphate, guanosine 5'-monophosphate, and inosine 5'-monophosphate. Levels of nucleotides varied considerably amongst individual mothers and with stage of lactation. They could be further influenced by time of day and season and the mother's diet. Levels of free nucleotides varied between studies undertaken in different regions; however, in studies that measured total potentially available nucleotides levels, regional differences were not apparent. Some studies report higher amounts in colostrum and transition milk compared with mature milk, whereas other studies report the converse. Recently, clinical studies showed that there are benefits to supplement nucleotides in infant formula. Although comparing data in the literature remains a challenge because of different milk collection methodologies and measurement protocols used by different studies, the information may provide insights for designing of formula products for infant at different stages of development.

Background The nutrients in human milk, particularly amino acids and minerals, are important for infant growth and development. Since there are few reports of amino acids and minerals in Chinese breast milk, we conducted this study to establish a representative preliminary database of breast milk nutrients in Chinese breast milk. In this study, we collected breast milk from healthy mothers in seven cities in western, southern and central China. The composition, content and proportion of total amino acids and ten elements (potassium, sodium, calcium, magnesium, iron, zinc, manganese, copper, selenium and phosphorus) in human milk in different lactation stages were investigated. Results In this study, it was found that the content of total essential amino acids (671.47 mg 100 mL-1 ) in Chinese breast milk was higher compared with the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) (574 mg 100 mL-1 ), but the content of leucine (LEU) (129.01 mg 100 mL-1 ) and cysteine (CYS) (20.31 mg 100 mL-1 ) was much lower than that recommended by ESPGHAN. Moreover, it was found that the content of most of these ten elements decreased during lactation, and the content of calcium in Chinese breast milk was lower compared with ESPGHAN. In addition, the content of selenium (7.23-20.55 mg 1000 mL-1 ) in breast milk from the three cities Nanchang, Shanghai and Guangzhou in China was much higher than that recommended by ESPGHAN. Conclusions In a word, amino acids and minerals in Chinese human milk showed a significant difference from other countries. Human milk meal or infant food should be regulated to meet the requirements of the infant and to maintain the balance of the amino acids and minerals. © 2020 Society of Chemical Industry.

Autophagy-impairment is involved in the pathological process of chronic obstructive pulmonary disease (COPD), and relates to inflammation and emphysema in lung injury. This study aimed to elucidate the protective effect of S-Allylmercapto-N-acetylcysteine (ASSNAC) against COPD via regulating the autophagy. Firstly, porcine pancreatic elastase (PPE)-induced COPD model in A549 cells was established, and ASSNAC was verified to alleviate the autophagy-impairment from the results of western blotting analysis of LC3BⅡ/Ⅰ and monodansylcadaverine (MDC) staining of autophagosome. Secondly, Balb/c mice were stimulated by PPE to induce the COPD model in vivo. The histological analysis of lung tissues presented that ASSNAC could alleviate the lung injury induced by PPE. Thirdly, the secretions of NO, TNF-α and IL-1β in serum and BALF were reduced by ASSNAC compared with the PPE group. Finally, the mechanism of therapeutic effects of ASSNAC against COPD through regulating the autophagy-impairment was clarified. That is, ASSNAC inhibits the phosphorylation of PI3K/Akt/mTOR signaling pathways. In a word, this research provides a reference for ASSNAC to be an effective drug for pulmonary diseases.

With the increasingly wide range of Internet, the traditional enterprise management model faces enormous challenges, and the user needs are increasingly personalized. How to promote employees to actively promote product services has become an urgent problem for enterprises. Taking Haier Group’s financial control model as the study object, the paper aims to deeply explore how Haier’s financial control model supports the co-evolution of product services and employee competence. The study could help the enterprises to build a financial control model that supports co-evolution of product services and employee competence.

A few studies suggested high stereo-specifically numbered (sn)-2 palmitate in a formula might favor the gut Bifidobacteria of infants. The initial colonization and subsequent development of gut microbiota in early life might be associated with development and later life functions of the central nervous system via the microbiota–gut–brain axis, such as children with autism. This study aims to assess the hypothesized effect of increasing the amount of palmitic acid esterified in the sn-2 position in infant formula on neurodevelopment in healthy full-term infants and to explore the association of this effect with the altered gut Bifidobacteria. One hundred and ninety-nine infants were enrolled in this cluster randomized clinical trial: 66 breast-fed (BF group) and 133 formula-fed infants who were clustered and randomly assigned to receive formula containing high sn-2 palmitate (sn-2 group, n = 66) or low sn-2 palmitate (control group, n = 67), where 46.3% and 10.3% of the palmitic acid (PA) was sn-2-palmitate, respectively. Infants’ neurodevelopmental outcomes were measured by the Ages and Stages Questionnaire, third edition (ASQ-3). Stool samples were collected for the analysis of Bifidobacteria (Trial registration number: ChiCTR1800014479). At week 16, the risk of scoring close to the threshold for fine motor skills (reference: scoring above the typical development threshold) was significantly lower in the sn-2 group than the control group after adjustment for the maternal education level (p = 0.036) but did not differ significantly versus the BF group (p = 0.513). At week 16 and week 24, the sn-2 group (week 16: 15.7% and week 24: 15.6%) had a significantly higher relative abundance of fecal Bifidobacteria than the control group (week 16: 6.6%, p = 0.001 and week 24:11.2%, p = 0.028) and did not differ from the BF group (week 16: 14.4%, p = 0.674 and week 24: 14.9%, p = 0.749). At week 16, a higher relative abundance of Bifidobacteria was associated with the decreased odds of only one domain scoring close to the threshold in the formula-fed infants group (odds ratio (OR), 95% confidence interval (CI): 0.947 (0.901–0.996)). Elevating the sn-2 palmitate level in the formula improved infants’ development of fine motor skills, and the beneficial effects of high sn-2 palmitate on infant neurodevelopment was associated with the increased gut Bifidobacteria level.

Breast milk proteins are essential to infants as they provide nutrition and protection. This study evaluated multiple factors that might influence breast milk proteins to identify the determinants that lead to inter-individual and longitudinal differences.Five major breast milk proteins (β-casein, α-lactalbumin, lactoferrin, serum albumin and κ-casein) from breast milk samples collected from 55 mothers in three cities (Hohhot, Wuhan and Qingdao) in China were analyzed using a validated ultraperformance liquid chromatography-mass spectrometry method. Various factors were statistically evaluated for their associations with breast milk proteins: mother's age, parity, delivery mode, infant gender and infant birthweight.Although decreased in concentrations, the proportions of β-casein and α-lactalbumin increased from colostrum (33.8% and 26.8%) to mature milk (40.3% and 31.6%), respectively. Mothers of older age were found to produce a lower concentration of total protein. Compared with vaginal delivery, caesarean section was associated with lower concentrations of κ-casein, lactoferrin and β-casein in mature milk. Infant gender influenced breast milk proteins in colostrum: mothers who delivered a girl tended to produce more κ-casein, lactoferrin and total protein. Furthermore, regional differences were found, and mothers from Hohhot produced significantly higher concentrations of α-lactalbumin and lactoferrin than those from Qingdao and Wuhan. This regional difference might be linked to the different dietary patterns of these mothers among cities.Our study deepens the understanding of breast milk protein dynamics in Chinese population and provides evidence on potential determinants, which can serve as guidance for infant nutrition optimization.

The paper use the core principles of critical realism (CR) and Bourdieu’s practice theory to argue how symbolic value arise in the real domain from the relation between the complex assemblages of s...

In order to investigate the fatty acid composition and distribution in colostrum and mature milk, breast milk samples and 24 h food records were obtained from 65 lactating women across three regions in China (Inner Mongolia, North Jiangsu and Guangxi). Fatty acid methyl esters were prepared by standard methods and separated and identified by gas chromatography. Compared with the Chinese breast milk fatty acid data 10 years ago, SFA and trans fatty acids (TFA) in breast milk decreased, while PUFA increased in the present study. Most SFA (C16:0, C15:0, C14:0), cis-C16:1 and several LC-PUFA (C22:5n-3 and C22:6n-3) were predominantly acylated at the sn-2 position. The cis-C17:1 and C22:6n-3 were distributed equally in three positions of triacylglycerol (TAG). Whereas, TFA, conjugated linoleic acids (CLA), cis-C18:1, C18:2n-6, C18:3n-3 and C20:5n-3 were acylated at the sn-1, 3 positions of TAG in human milk. The composition of fatty acids in breast milk was closely related to the diet of lactating mothers. PUFA in breast milk was negatively correlated with the intake of protein, fat and meat, but positively correlated with the intake of carbohydrates. MUFA of human milk was negatively correlated with the intake of dairy products, eggs, fish and shrimp. SFA in breast milk was positively correlated with the maternal intake of meat. In addition, the present results showed that the composition of total fatty acids and sn-2 fatty acids in breast milk varied with the lactation period and the geographical regions in China; however, the regiospecific fatty acid profile seemed not to be affected by the lactation time and regions, although the quantities at each position could be changed.

In this work, a novel ascorbic acid (AA) ratiometric biosensor was prepared by using the PCN-333 (Al) metal-organic frameworks (MOFs) (PCN stands for porous coordination network) to encapsulate Ketjen black (KB) as catalyst for catalyzing oxidation of AA and thionine (Thi) as an internal reference signal simultaneously. The encapsulation of KB and Thi in the pores of PCN-333 (Al) MOFs not only improved efficiency of KB and Thi greatly because PCN-333 (Al) MOFs could effectively avoid the cohesion or aggregation of KB and Thi on electrode surface but also enhanced the stability of biosensors because they were immobilized in the pore firmly. Furthermore, PCN-333 (Al) MOFs could also selectively accumulate target analytes into their pores to enhance the selectivity of biosensors. The oxidation peak current of AA catalyzed by KB at −0.05 V increased with the increasing concentration of AA, while the oxidation peak current of Thi at −0.24 V kept constant, which resulted in a novel ratiometric biosensor for AA detection. The ratiometric biosensor exhibited a wider linear range from 14.1 ± 0.2 to (5.5 ± 0.1) х103 μM (R2 = 0.998) and a lower detection limit of 4.6 ± 0.1 μM with high accuracy, selectivity, reproducibility and sensitivity. The ratiometric electrochemical approach is not only a new method for AA detection but also opens a new way for sensitive detection of other analytes.

Whey, an essential source of dietary nutrients, is widely used in dairy foods for infants. A total of 584 whey proteins in human and bovine colostrum and mature milk were identified and quantified by the isobaric tag for relative and absolute quantification (iTRAQ) proteomic method. The 424 differentially expressed whey proteins were identified and analyzed according to gene ontology (GO) annotation, Kyoto encyclopedia of genes and genomes (KEGG) pathway, and multivariate statistical analysis. Biological processes principally involved biological regulation and response to stimulus. Major cellular components were extracellular region part and extracellular space. The most prevalent molecular function was protein binding. Twenty immune-related proteins and 13 proteins related to enzyme regulatory activity were differentially expressed in human and bovine milk. Differentially expressed whey proteins participated in many KEGG pathways, including major complement and coagulation cascades and in phagosomes. Whey proteins show obvious differences in expression in human and bovine colostrum and mature milk, with consequences for biological function. The results here increase our understanding of different whey proteomes, which could provide useful information for the development and manufacture of dairy products and nutrient food for infants. The advanced iTRAQ proteomic approach was used to analyze differentially expressed whey proteins in human and bovine colostrum and mature milk.

Milk fat globule membrane (MFGM) proteins have important biological functions, such as anticancer properties, preventing Helicobacter pylori infection, and immune functions. However, the full range of colostrum MFGM proteins has not completely identified. In this study, extracted colostrum MFGM proteins were identified and quantified using the isobaric tags for relative and absolute quantitation proteomic method. A total of 411 human and bovine colostrum MFGM proteins were identified and quantified. These MFGM proteins were classified according to gene ontology annotation. The major biological processes involved were response to stimulus, representing 19 % of total proteins; establishment of localization (18 %); and cellular component organization (17 %). The most prevalent cellular components were intracellular representing 19 %, and intracellular part represented 18 %. The most prevalent molecular function was protein binding (46 %). Hierarchical clustering was used for the quantitative analysis of colostrum MFGM levels in humans and bovines. Furthermore, one-factor analysis of variance identified 26 differentially expressed proteins. The differentially expressed proteins were involved in three major pathways: calcium signaling pathway, phagosome, and FcγR-mediated phagocytosis. This study examined the expression changes and functional differences of colostrum MFGM proteins between humans and bovines to provide useful information and potential research directions for the dairy industry.

Human and bovine milk fat globule membrane (MFGM) proteins have been identified and characterized; however, their glycosylation during lactation remains unclear. We adopted a glycoproteomics approach to profile and compare MFGM N-glycoproteomes in human and bovine milk during lactation. A total of 843, 718, 614, and 273 N-glycosite peptides corresponding to 465, 423, 334, and 176 glycoproteins were identified in human colostrum, human mature milk, bovine colostrum, and bovine mature milk, respectively. The biological functions of these MFGM N-glycoproteins were revealed through bioinformatics. Substantial differences were observed between human and bovine milk, and immune-related MFGM N-glycoproteins varied between colostrum and mature milk from both species. Our results expand current knowledge of MFGM N-glycoproteomes, and further demonstrate the complexity and biological functions of MFGM N-glycosylation. These data can provide references for the application of bovine MFGM N-glycoproteins in infant formula to resemble human milk and in functional foods.

In this work, we carried out a case-control study to examine the role of CTLA4 49 A→G (rs231775), IL1B -511 C→T (rs16944), IL10 -1082 A→G (rs1800896), IL10 -592 A→C (rs1800872), IL12B 3’UTR 1188 A→C (rs 3212227) and IL18 105 A→C (rs549908) polymorphisms on the risk of Hashimoto’s thyroiditis among Han Chinese. The six polymorphisms were genotyped on 1,114 patients with Hashimoto’s thyroiditis and 1,308 age- and sex-matched controls. Odds ratios (ORs) were then calculated via logistic regression model to determine the association present. It was shown that CTLA4 49 A→G and IL10 -1082 A→G polymorphisms were significantly associated with an increased risk of Hashimoto’s thyroiditis, while a significant association was not observed for the four remaining polymorphisms. The variant allele, heterozygous genotype and variant genotype of the CTLA4 polymorphism had an OR of 1.199 (95%CI=1.070-1.344, P=0.002), 1.397 (95%CI=1.125-1.734, P=0.002) and 1.493 (95%CI=1.181-1.887, P=0.001) respectively, while the OR values for the IL10 -1082 A→G polymorphism were 1.354 (95%CI=1.164-1.575, P IL10 -592 A→C polymorphism, the association was only significant at the allele level (OR=1.199, 95%CI=1.064-1.351, P=0.003), but not at the genotype level (P>0.0083 after Bonferroni correction). In conclusion, CTLA4 49 A→G, IL10 -1082 A→G and IL10 -592 A→C polymorphisms may potentially contribute to the susceptibility of Hashimoto’s thyroiditis.

International audience; The Paris Agreement appeals to all countries around the world for reducing greenhouse gas emissions. Nowadays, logistics companies do not only consider improving service quality and reducing operating costs but also should take a particular corporate social responsibility: reducing greenhouse gas emissions. Minimizing greenhouse gas emissions has been emerged in vehicle routing problems in many investigations, while most of the models are deterministic. The feedback from logistics practice reveals that the workers often encounter uncertainties when providing services to customers. The decisions made without considering uncertainties show less robustness when carrying the logistics activities according to the given scheduling. Consequently, in this study, this is the first attempt to develop a relative robust optimization model for a vehicle routing problem with synchronized visits and uncertain scenarios considering greenhouse gas emissions. In this study the greenhouse gas emissions is evaluated by the fuel consumption cost. Due to the NP-hard of the studied model, a hybrid tabu search and simulated annealing is proposed to solve it. The experimental results on the popularly used benchmark instances demonstrate that the proposed algorithm is efficient and effective. The comparison performed among the solutions obtained by different types of models has highlighted the importance of considering uncertainties. Then, the sensitivity analysis is performed to observe the change of fuel consumption cost with varying types of vehicles. Statistical analysis is carried out to further validate the different models. Finally, two bi-objective optimization based scenarios have been established to demonstrate the trade-off between GHG emissions and robustness indicators. The proposed models can be applied to some practical applications, such as logging truck routing planing.

Milk fat globule membrane (MFGM) proteins have many functions. To explore the different proteomics of human and bovine MFGM, MFGM proteins were separated from human and bovine colostrum and mature milk, and analyzed by the iTRAQ proteomic approach. A total of 411 proteins were recognized and quantified. Among these, 232 kinds of differentially expressed proteins were identified. These differentially expressed proteins were analyzed based on multivariate analysis, gene ontology (GO) annotation and KEGG pathway. Biological processes involved were response to stimulus, localization, establishment of localization, and the immune system process. Cellular components engaged were the extracellular space, extracellular region parts, cell fractions, and vesicles. Molecular functions touched upon were protein binding, nucleotide binding, and enzyme inhibitor activity. The KEGG pathway analysis showed several pathways, including regulation of the actin cytoskeleton, focal adhesion, neurotrophin signaling pathway, leukocyte transendothelial migration, tight junction, complement and coagulation cascades, vascular endothelial growth factor signaling pathway, and adherens junction. These results enhance our understanding of different proteomes of human and bovine MFGM across different lactation phases, which could provide important information and potential directions for the infant milk powder and functional food industries.

To assess the long-term clinical efficacy and safety of adding cilostazol (TAT) to conventional dual antiplatelet therapy (DAT) for patients undergoing drug-eluting stent (DES) implantation in coronary arteries.We performed PUBMED, MEDLINE, EMBASE, and Cochrane CENTRAL searches for randomized clinical trials of TAT versus DAT in patients after DES implantation with criteria to include trials with a follow-up of more than 6 months.Seven RCTs with a total of 3487 patients were included in this review. The meta-analysis showed that TAT was associated with a significant reduction in major adverse cardiac events (MACEs) (relative risk (RR)=0.66; 95% CI=0.50-0.88), target lesion revascularization (TLR) (RR=0.61, 95% CI=0.43-0.84), target vessel revascularization (TVR) (RR=0.53, 95% CI=0.37-0.75), in-stent restenosis (RR=0.64, 95% CI=0.44-0.85), in-segment restenosis (RR=0.58, 95% CI=0.43-0.79, P.01), in-stent late loss (LL) (standardized mean difference (SMD)=-0.21, 95% CI=0.32-0.17), and in-segment LL (SMD=-0.27, 95% CI=-0.38-0.16). TAT also did not appear to significantly alter any of the other meta-analysis secondary efficacy outcomes and had similar rates of bleeding, but TAT had significantly higher rates of rash, gastrointestinal side-effects, headache and drug discontinuation.Compared with standard DAT, the long-term use of TAT in patients after DES implantation gave more benefits in reducing the incidence of MACEs, TLR, TVR, in-stent and in-segment LL and restenosis without increasing bleeding but was associated with an increase in minor adverse events.

Phospholipids (PLs) and cholesterol in human milk (HM) are affected by lactation, and differential lipids are closely related to maternal diet. The contents of PLs and cholesterol in Chinese HM are quantified by gas chromatography and high performance liquid chromatography, respectively, and the relationship between differential lipids and the maternal diet is obtained by Pearson. The result shows that SFA, MUFA, and polyunsaturated fatty acid (PUFA) are not affected by lactation and geography for total fatty acids, but almost all sn‐2 fatty acids are influenced by geography and remain unchanged during lactation. Most SFAs show absolute sn‐2 selectivity and the majority of MUFAs and PUFAs are esterified at the sn‐1 position. Cholesterol (13.8–22.6 mg per 100 g milk) and 25‐hydroxycholesterol (0.45–1.01 mg per 100 g milk) increase significantly and remain constant during lactation, respectively, and they are affected by regions. In addition, the differential lipids (22:1n‐9, C9:0, trans‐PUFA, 22:4n‐6, etc.) of PLs are closely related to the maternal diet. PLs and cholesterol content differ from western research and infant formula, which will help to design an infant formula that is more suitable for Chinese babies in the future. Practical Application: Compared with PLs and cholesterol in western countries and infant formula, the specificity of Chinese HM can more accurately target the development of formulas suitable for the growth of Chinese infants. At the same time, according to the influence of the motherʼs diet on the composition of HM, it is more reasonable to guide the diet of the mother.

Exosomes are membranous vesicles found in biological fluids with important functions. However, milk-derived exosome proteins from humans and bovines have not been studied in detail. The advanced iTRAQ proteomic approach was used to analyze milk-derived exosomes in human and bovine colostrum and mature milk samples. A total of 920 milk exosome proteins were identified and quantified. Among these, 575 differentially expressed exosome proteins (P

Macronutrient contents in human milk are the common basis for estimating these nutrient requirements for both infants and lactating women. A mid‐infrared human milk analyser (HMA, Miris, Sweden) was recently developed for determining macronutrient levels. The purpose of the study is to compare the accuracy and precision of HMA method with fresh milk samples in the field studies with chemical methods with frozen samples in the lab. Full breast milk was collected using electric pumps and fresh milk was analyzed in the field studies using HMA. All human milk samples were thawed and analyzed with chemical reference methods in the lab. The protein, fat and total solid levels were significantly correlated between the two methods and the correlation coefficient was 0.88, 0.93 and 0.78, respectively (p 0.05). There was no statistically significant difference in the mean total solid concentration (12.2 g 100 mL(−1)vs 12.3 g 100 mL(−1), p > 0.05). Overall, HMA might be used to analyze macronutrients in fresh human milk with acceptable accuracy and precision after recalibrating fat and protein levels of field samples.

Mistletoe (Viscum album) lectins, which are classified as a type II ribosome-inactivating protein (RIP) due to their unique biological function and the potential medical and therapeutic application in cancer cells, receive a rising attention. The heterodimeric glycoproteins contain the Achain with catalytic activity and the B-chain with sugar binding properties. In recent years, studies involving the lectins from the white berry European mistletoe (Viscum album) and the yellow berry Korean mistletoe (Viscum album coloratum) have been described. However, the detailed mechanism in exerting unique cytotoxic effect on cancer cells still remains unclear. Here, we aim to understand and define the molecular basis and biological effects of the type II RIPs, through the studies of the recombinant Korean mistletoe lectin. To this end, we expressed, purified the recombinant Korean mistletoe lectin (rKML), and investigated its molecular characteristics in vitro, its cytotoxicity and ability to induce apoptotic cell death in cancer cells. To gain structural basis for its catalytic activity and sugar binding properties, we performed homology modeling studies based on the high degree of sequence identity and conserved secondary structure prediction between Korean and European, Himalayan mistletoe lectins, and Ricin. Accepted version

156 p. Mistletoe (Viscum album) lectins exert unique biological effects inhibiting protein synthesis through the cleavage of ribosomal RNA and are classified as type-II ribosome-inactivating proteins and receive a rising attention due to their potential medical and therapeutic applications in cancer therapy. The heterodimeric glycoproteins contain the A-chain with RNA cleaving catalytic activity and the B-chain with sugar-binding properties. DOCTOR OF PHILOSOPHY (SBS)