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Circular RNAs (circRNAs) are a type of special noncoding RNA. circRNAs are highly stable and are found mainly in the cytoplasm. Most circRNAs are conserved and usually exhibit tissue specificity and timing specificity. In addition to the regulation mode of competitive endogenous RNA (ceRNA), circRNAs can also bind to RNA-binding proteins (RBPs), regulate alternative splicing, encode proteins or polypeptides, and regulate the expression of parent genes affecting biological pathways in which coded proteins are involved. Autophagy is an important cellular mechanism that plays an essential role in normal cell physiological processes and in diseases, especially tumors. Studies reported that circRNAs have an important effect on autophagic processes. What are the detailed biological functions and mechanisms of circRNAs in autophagy? In this article, we summarize the relationship between circRNAs and autophagy and the regulatory function and mechanism (especially as microRNA [miRNA] sponges and binding to RBPs) of circRNAs in autophagy. In addition, we discuss the dysregulation and functional and clinical applications of autophagy-associated circRNAs in a variety of diseases. Autophagy-associated circRNAs have the potential to be essential biomarkers of diagnosis and treatment and to be beneficial to the research and development of targeted drugs for tumor or non-tumor diseases., Graphical Abstract, In this review, the authors summarize the relationship between circRNAs and autophagy. Moreover, the authors discuss the dysregulation and clinical applications of autophagy-associated circRNAs in a variety of diseases. Autophagy-associated circRNAs will have superior prospects as tumor prognosis markers, diagnostic markers, and therapeutic targets for tumor drug resistance in the future.

Background: Phthalates may disturb metabolic homeostasis in the liver by interfering with the peroxisome proliferator-activated receptors (PPARs). However, the role of hepatic macrophages in the lipid metabolic dysregulation induced by diethylhexyl phthalate (DEHP) remains unclear. Objectives: We aimed to evaluate the respective role of hepatocyte- and macrophage-specific PPARγ in the hepatotoxicity induced by DEHP. Methods: Wild-type (WT), hepatocyte-specific PPARγ knockout (Hep-KO), and macrophage-specific PPAR knockout (Mac-KO) mice were administered DEHP (625mg/kg body weight) by daily gavage for 28 d, followed by hepatotoxicity examination and macrophage analysis. RNA sequencing and lipid metabolomic analysis were used to characterize the molecular changes in mouse liver. Mouse bone marrow-derived macrophages (BMDMs) and human monocytic THP-1 cell-derived macrophages were used to investigate the mechanistic regulation of macrophages’ polarization by DEHP and mono(2-ethylhexyl) phthalate (MEHP). Results: The levels of hepatic steatosis and triglyceride were significantly higher in the mice treated with DEHP compared with the control mice in the WT and Hep-KO model. Lipid accumulation induced by DEHP was notably attenuated in the Mac-KO mice, but M2-polarization of hepatic macrophages in the Mac-KO mice was significantly higher compared with the WT mice under DEHP treatment. The M2-polarization of BMDMs and human macrophages was suppressed by DEHP and MEHP. Transcriptomic and lipidomic data suggested lower levels of lipid biosynthesis, fatty acid oxidation, and oxidative phosphorylation in the Mac-KO mice compared with the WT and Hep-KO mice under DEHP treatment. Conclusions: Our data suggested that the orchestrated activation of PPARα and PPARγ by MEHP may reprogram hepatic macrophages’ polarization, thereby affecting lipid homeostasis in the mouse liver. Although this conclusion was based on studies conducted in mice and in vitro, these findings may aid in elucidating the health effect of environmental phthalate exposure. https://doi.org/10.1289/EHP9373

Background The poor prognosis of esophageal squamous cell carcinoma (ESCC) highlights the need for novel strategies against this disease. Our previous study suggested the involvement of CCL2 and tumor associated macrophages (TAMs) in esophageal carcinogenesis. Despite the recognition of TAMs as a promising target for cancer treatment, mechanisms underlying its infiltration, activation and tumor-promotive function in ESCC remain unknown. Methods Human esophageal tissue array and TCGA database were used to evaluate the clinical relevance of CCL2 and TAMs in ESCC. F344 rats and C57BL/6 mice were treated with N-nitrosomethylbenzylamine (NMBA) to establish orthotopic models of esophageal carcinogenesis. CCL2/CCR2 gene knockout mice and macrophage-specific PPARG gene knockout mice were respectively used to investigate the role of infiltration and polarization of TAMs in ESCC. CCL2-mediated monocyte chemotaxis was estimated in malignantly transformed Het-1A cells. THP-1 cells were used to simulate TAMs polarization in vitro. RNA-sequencing was performed to uncover the mechanism. Results Increasing expression of CCL2 correlated with TAMs accumulation in esophageal carcinogenesis, and they both predicts poor prognosis in ESCC cohort. Animal studies show blockade of CCL2-CCR2 axis strongly reduces tumor incidence by hindering TAMs recruitment and thereby potentiates the antitumor efficacy of CD8+ T cells in the tumor microenvironment. More importantly, M2 polarization increases PD-L2 expression in TAMs, resulting in immune evasion and tumor promotion through PD-1 signaling pathway. Conclusion This study highlights the role of CCL2-CCR2 axis in esophageal carcinogenesis. Our findings provide new insight into the mechanism of immune evasion mediated by TAMs in ESCC, suggesting the potential of TAMs-targeted strategies for ESCC prevention and immunotherapy.

The immune microenvironment has profound impacts on the initiation and progression of colorectal cancer (CRC). Therefore, the goal of this article is to identify two robust immune subtypes in CRC, further provide novel insights for the underlying mechanisms and clinical management. In this study, two CRC immune subtypes were identified using the consensus clustering of immune-related gene expression profiles in the meta-GEO dataset (n = 1,198), and their reproducibility was further verified in the TCGA-CRC dataset (n = 638). Subsequently, we characterized the immune escape mechanisms, gene alterations, and clinical features of two immune subtypes. Cluster 1 (C1) was defined as the “immune cold subtype” with immune cell depletion and deficiency, while cluster 2 (C2) was designed as the “immune hot subtype”, with abundant immune cell infiltration and matrix activation. We also underlined the potential immune escape mechanisms: lack of MHC molecules and defective tumor antigen presentation capacity in C1, increased immunosuppressive molecules in C2. The prognosis and sensitivity to 5-FU, Cisplatin and immunotherapy differed between two subtypes. According to the two immune subtypes, we developed a prognosis associated risk score (PARS) with the accurate performance for predicting the prognosis. Additionally, two nomograms for overall survival (OS) and disease-free survival (DFS) were further constructed to facilitate clinical management. Overall, our research provides new references and insights for understanding and refining the CRC.

The increasing application of zinc oxide nanoparticles (ZnO NPs) in consumer products has raised concerns about the potential health risks in human. It is crucial to understand the toxicokinetic information of ZnO NPs, especially the differences between NPs and non-nano form material. This study investigated the toxicokinetic profile of ZnO NPs and food grade bulk-sized ZnO in rats after single or repeated oral dosages. For single oral administration of ZnO suspensions at 350 mg/kgbw, the Zn content in blood and tissues showed no elevation, the majority of ZnO particles were eliminated via feces within 48 h. For repeated oral exposure to ZnO suspensions at 350 mg/kgbw or ZnSO4 solution at 700 mg/kgbw for 90 days, elevated Zn levels were observed in liver, kidney, and bone in all three treatment groups, the Zn level recovered to normal level in liver and kidney, but not in bone, after a recovery period. ZnO NPs and bulk-sized ZnO showed similarity in toxicokinetics in rats, regardless of exposure duration or gender. ZnO particles shared a similar biodistribution profile with ZnSO4, and were likely to be absorbed mostly in ionic forms.

Additional file 4:Â Supplementary Table S1. Samples list in the ESCC cohort (100 cases). Supplementary Table S2. ESCC samples list from TCGA database. Supplementary Table S3. Mouse (m) and Human (h) Primers for PCR. Supplementary materials S4. Reagents and antibodies. Supplementary table S5. Uni- and multi-variate COX proportional hazard model analysis for overall survival of ESCC patients in cohort II. Supplementary table S6. KEGG pathway enrichment by GSEA analysis.

Additional file 2. Supplementary materials. Authentication of cell lines.

Additional file 1: Supplementary Figure S1. Transcriptomic analysis on the NMBA-induced carcinogenesis in ESCC rat model. (a) Enrichment of Gene. Ontology (GO). (b) Enrichment of signaling pathway. The Top 30 enriched terms are shown. (c). Heatmap of chemokines and receptors in carcinogenesis. Microarray data was available on Gene Expression Omnibus (GEO) database under the accession number GSE90464. Supplementary Figure S2. Gating strategy in flow cytometry analysis for tumors. The antibodies used for flow cytometry has been list in Supplementary Table S4. Supplementary Figure S3. Escalating expression of CCL2 in the NMBA-induced ESCC carcinogenesis cell model. (a) Establishment of malignant transformation cell model with NMBA-treatment (10 μM, 25 weeks) in Het-1A cells. (b) Genes expression with the pattern of Continuous increasing over transformation. (c) Enriched pathways for the over-expressed genes. (d) Heatmap shows increased expression of CCL2 and correlated genes. Supplementary Figure S4. ESCC mouse model. (a) CCL2 expression and TAMs accumulation was continuously increase in mouse forestomach during carcinogenesis. (b) Heatmap of Gene expressions by RNA-sequencing with tumors harvested from the CCR2−/− mouse model. Supplementary Figure S5. The effect of CCL2 on pro-death signaling, proliferation and ESCC markers. (a) Heatmap showing relative expression of ESCC markers in normal and ESCC tissues of animal models. (b) The expression of EGFR, BRCA1, CCND1, Myc, Met, TP63, and CD44 were determined with q-PCR in CCL2−/− mouse model. (c) TE-1 cells were treated with CCL2 (0, 10, 50, 500 ng/ml) for 24 h and gene expression was determined by q-PCR. Supplementary Figure S6. Expression of PD-L1 and PD-L2 in polarized macrophages. (a) Differential expression of PD-L1 and PD-L2 in HLA-DR + CD209- M1 macrophages and HLA-DR-CD209+ M2 macrophages. (b) Polarization was not induced by culture with conditioned medium neither by co-culture with cells. THP-1 cells were treated with PMA to induce M0 macrophages as described in Supplementary materials and methods, then incubated with conditioned medium or co-cultured with indicated cells for 72 h. Cells were harvested for analysis with flow cytometry.

TT51 is a transgenic strain of Bt rice generated by fusing a synthetic CryAb/Ac gene into MingHui rice. In this study, rats from F0, F1, and F2 generations were fed a diet with 60% TT51 rice, MingHui rice, or nominal-origin rice. The study focused on developmental immunotoxicity in F1 and F2 offspring after long-term consumption of TT51. A wide range of immunological parameters was monitored in this two-generation study on reproductive toxicity. The experiments were performed on F1 and F2 offspring at postnatal days 21 and 42. No adverse clinical effects were observed in any of the experimental groups. In addition, histopathology observations and immunotoxicity tests, including hematological indicators, spleen lymphocyte subsets, natural killer cell activity, lymphoproliferative response, and plaque-forming cell assay, revealed no significant difference between the groups. These results indicated that developmental immunotoxicity was not associated with a diet of transgenic Bt rice TT51, compared to the parental MingHui rice.

In the current study, thermal-denatured whey protein-milk fat emulsion gel microparticles (WPI-EGs) were used as stabilizers and fat replacers in low-fat yogurt. The effects of emulsion gel microparticles were studied on the texture, rheology, microstructure, and sensory evaluation of low-fat yogurt. The results showed that yogurt with WPI-EGs had a better (p

11TPY001 is a transgenic maize that expresses the Aspergillus niger phyA2 gene which could significantly improve phosphorus bioavailability in monogastric animals. The present study was conducted to investigate the potential health effects of phytase transgenic maize 11TPY001 through a 90-day subchronic rodent feeding study. Maize grains from 11TPY001 or its parental counterpart maize OSL963 were incorporated into rodent diets at 12.5%, 25% and 50% concentrations by mass and administered to Sprague-Dawley rats (n = 10/sex/group) for 90 days. An additional control group of rats (n = 10/sex/group) were fed with common maize Zhengdan958 diets at 50% by mass. All formulated diets were nutritionally balanced. Body weights, food intake, hematology, serum chemistry, absolute and relative organ weights were measured, and gross as well as microscopic pathology were examined. Compared with rats fed OSL963 maize and the common maize diet groups, no adverse diet-related differences were observed in rats fed 11TPY001 maize diets with respect to clinical signs of toxicity, body weight/gain, food consumption/efficiency, hematology, clinical chemistry, organ weights, and gross and microscopic pathology. Under the conditions of this study, the results indicated that 11TPY001 did not cause any treatment related adverse effects in rats compared with its non-transgenic parental maize OSL963.

BACKGROUND The use of power ultrasound as a pretreatment to enhance the hydrolysis of milk protein concentrate (MPC) and subsequent angiotensin converting enzyme (ACE) inhibitory activity has been studied. Liquid chromatography was used to analyse peptide profiles of Neutrase-derived MPC hydrolysates after pretreatment at 0, 1, 3, 5 and 8 min at an ultrasound power level of 800 W. RESULTS The peptide profiles indicated an increase in number of peptides when ultrasound pretreatment was applied. There was also an increase in the degree of hydrolysis of MPC hydrolysates. The profiles indicated that new small peptides in ultrasound pretreated samples (1–5 min) which were not present in the control samples and 8 min pretreated samples, could be responsible for increased ACE inhibitory activity. These small peptides were digested in the 8 min pretreated samples. CONCLUSION Ultrasound pretreatment of MPC increases the ACE inhibitory activity of the hydrolysates because of the production of new small peptides. This can be used as a means to derive potent ACE inhibitory peptides at industrial scale in complex protein sources. © 2014 Society of Chemical Industry

A batch mode, pilot-scale process, involving ultrasound pretreatment (USP), enzymolysis, membrane filtration and drying was investigated for the production of angiotensin converting enzyme (ACE) inhibitory and antioxidative peptides from milk protein concentrate (MPC). The MPC solutions (2% or 5% protein) were hydrolyzed for 2 h with Neutrase at enzyme-to-substrate ratio of 1:50 (w/w) in 50 L batches after USP for 4 min at 800 W. Ultrafiltration (8 and 3.5 kDa membranes) and nanofiltration (0.2 kDa membrane) were done to produce 4 fractions (F1, >8 kDa; F2, 3.5–8 kDa; F3, 0.2–3.5 kDa; and F4

This study investigated the inhibitory effects of Lactobacillus casei AST18 as a biocontrol agent on fungi spoilage in yogurt. In a yogurt preservation period experiment and mould-proof accelerated testing at 4 °C, the addition of 2% (v/v) L. casei AST18 in yogurt completely inhibited mould growth; mould growth was significantly delayed and spore germination was inhibited at 30 °C. The addition of L. casei AST18 improved the quantity of Lactobacillus , but the number of Streptococcus lactis in 2% AST18-added yogurt decreased by 1.0 Log (cfu/mL) compared with that in the blank group. L. casei AST18 exerted no significant influence on viscosity, water holding capacity, sensory quality, pH and titratable acidity. The post-acidification effect of L. casei AST18 was low. L. casei AST18 conspicuously inhibited the growth of filamentous fungi. Therefore, L. casei AST18 can be used as a bioprotective culture in yogurt to prevent fungal growth and extend shelf life.

Studies were conducted on ultrasound pretreatment of milk protein concentrate (MPC) before enzyme hydrolysis in order to produce hydrolysates with potent angiotensin converting enzyme (ACE) inhibitory activity. The effects of three independent variables of ultrasound pretreatment time (min), hydrolysis time (h) and enzyme-to-substrate ratio (%) on ACE inhibition as determined by central composite rotatable design were investigated in vitro. Optimization was achieved by response surface method. All the independent variables showed significance at 95% confidence level in contributing to ACE inhibition. According to response surface analysis, the optimum conditions for producing hydrolysates with the highest ACE inhibition were ultrasound pretreatment time, hydrolysis time and enzyme-to-substrate ratio of 4.11 min, 2.32 h and 2.33%, respectively. Under these optimal conditions, the theoretical ACE inhibition was 0.044 mg mL− 1. Model validation yielded satisfactory results indicating relevance of the model to explain ACE inhibition while ultrasound pretreatment showed strongest effect on ACE inhibition of MPC hydrolysates. Industrial relevance Milk protein concentrate has reportedly produced inferior bioactive compounds when compared to other milk proteins such as whey protein concentrate and sodium caseinate. Through the use of ultrasound pretreatment, milk protein concentrate can be used to produce more potent ACE inhibitory fractions comparable to those from non-aggregated milk protein sources. The use of short ultrasound pretreatment time offers an attractive route for industrial production of bioactive compounds from milk protein concentrate and other complex protein sources.

The increasing use of rare-earth elements (REE) and their compounds has led to their accumulation in the environment and has raised concern about their safety. The toxic effects of REE such as lanthanum are largely unknown; genotoxicity studies have been limited and results are controversial. We evaluated the genotoxicity of lanthanum nitrate (La(NO3)3) in several in vitro and in vivo tests, including bacterial reverse mutation assay (Ames test), mouse bone marrow micronucleus assay, and chromosome aberration assay. La(NO3)3 was not mutagenic in the Ames test. La(NO3)3 did not increase the frequencies of bone marrow micronuclei or chromosome aberration in the mouse after repeated treatments at oral doses up to 735 (females) and 855mg/kg (males). The compound did not increase the frequency of chromosome aberrations in CHO cells in vitro. These results indicate that lanthanum is not a genotoxic hazard.

trans-Resveratrol (resveratrol) has been shown to have beneficial effects on the cardiovascular system in a number of studies. It is, however, unclear whether this naturally occurring compound can protect against cardiac hypertrophy. The aim of the present study was to investigate the effects of resveratrol on cardiac hypertrophy in vivo and the potential underlying mechanisms involving endothelin (ET), angiotensin (Ang) II and nitric oxide (NO) in partially nephrectomized rats. Animal models bearing cardiac hypertrophy were replicated in male Sprague-Dawley rats following partial nephrectomy (PNX). Resveratrol (10 or 50 mg/kg) was administered to rats by gavage for 4 weeks. Simultaneous PNX and sham operation controls were simultaneously established in the present study. The systolic blood pressure (SBP) of rats was measured at baseline and, along with heart weight, after 4 weeks treatment. Serum ET-1, AngII and NO concentrations were determined. In the present study, it was shown that, compared with rats in the sham-operated group, rats in the PNX group had significantly higher SBP (154.1 +/- 22.7 mmHg), heart weight (1.69 +/- 0.24 g) and serum ET-1 (125.70 +/- 26.27 pg/mL) and AngII serum concentrations (743.63 +/- 86.50 pg/mL), whereas serum NO concentrations were lower (21.1 +/- 6.9 micromol/L; all P < 0.05). These values in the sham control group were 114 +/- 10 mmHg, 1.28 +/- 0.13 g, 52.44 +/- 21.85 pg/mL, 528.7 +/- 158.5 pg/mL and 53.21 +/- 23.87 micromol/L, respectively. After 4 weeks treatment with 50 mg/kg resveratrol, SBP, heart weight and ET-1 and AngII concentrations had decreased to 135.4 +/- 15.8 mmHg, 1.39 +/- 0.15 g, 97.11 +/- 26.74 pg/mL and 629.64 +/- 116.18 pg/mL, respectively. However, the serum NO concentration had increased to 40.1 +/- 14.6 micromol/L. These values were significantly different from those obtained for the PNX group. In conclusion, trans-resveratrol appears to be able to protect against the increase in SBP and subsequent cardiac hypertrophy in vivo and the mechanisms responsible may involve, at least in part, modulation of NO, AngII and ET-1 production.

Iron-deficiency anaemia, a complication of end-stage renal disease (ESRD), is often treated with parenteral iron therapies that have been shown to produce dose-limiting hypotension in patients. ABT-870 (iron-(III)-hydroxide-oligosaccharide) is comprised of elemental iron complexed with oligosaccharide, a composition that we hypothesised would allow the hypotensive effects of parenteral iron therapy to be overcome, thus allowing a rapid rate of infusion to be well tolerated. Mean arterial pressure (MAP) and heart rate (HR) were monitored in anaesthetized dogs following the infusion of ABT-870 and iron sucrose administered at doses of 7.1 and 21.3 mg/kg using a rapid 30 s infusion. ABT-870 and iron sucrose were also monitored at doses of 7.1, 21.3 and 50 mg/kg administered over a 10 min period. Sodium ferric gluconate complex (SFGC) was administered in an identical fashion at doses of 12.5 and 31.2 mg/kg. A 30 s rapid infusion of ABT-870 at doses of 7.1 and 14.3 mg/kg or a 10 min infusion of ABT-870 at doses of 7.1 and 21.3 mg/kg produced little effect on MAP and HR. Infusion of the highest dose of ABT-870 (50 mg/kg) produced no consistent hypotension, but did produce an increase in HR (maximal increase 35 +/- 9 b.p.m.), an effect that lasted only 15 min. A 30 s rapid infusion of iron sucrose at 7.1 mg/kg produced modest increases in MAP and HR (5 +/- 1 mmHg and 5 +/- 2 b.p.m., respectively). However, rapid infusion of iron sucrose at 14.3 mg/kg produced hypotension (to -8 +/- 1 mmHg below baseline) and exerted variable, biphasic effects on HR ranging from -16 to +50 b.p.m. Although 10 min infusion of iron sucrose at 7.1 mg/kg exerted little effect on MAP and HR, at doses of 21.3 and 50 mg/kg iron sucrose elicited a profound dose-dependent decrease in MAP (-34 +/- 11 and -83 +/- 5 mmHg, respectively) and a pronounced increase in HR ranging from 32 to 49 b.p.m. above baseline. A 10 min infusion of SFGC at doses of 12.5 and 31.2 mg/kg produced a dose-dependent decrease in MAP (-28 +/- 18 and -67 +/- 12 mmHg below baseline) and a marked increase in HR (26 +/- 11 and 94 +/- 15 b.p.m. above baseline). In conclusion, unlike iron sucrose and SFGC, high doses of ABT-870 failed to exert consistent hypotensive effects. These data demonstrate that ABT-870 may have a substantial therapeutic window and considerable clinical potential for iron-replacement therapy.

Autolysis of lactic acid bacteria (LAB) plays a vital role in dairy processing. During cheese making, autolysis of LAB affects cheese flavor development through release of intracellular enzymes and restricts the proliferation of cells in yogurt fermentation and probiotics production. In order to explore the mechanism of autolysis, the gene for the autolytic enzymes of L. bulgaricus, N-acetylmuramidase (mur), was cloned and sequenced (GenBank accession number: KF157911). Mur gene overexpression and gene knockout vectors were constructed based on pMG76e and pUC19 vectors. Recombinant plasmids were transformed into L. bulgaricus ljj-6 by electroporation, then three engineered strains with pMG76e-mur vector and fifteen engineered strains with pUC19-mur::EryBII were screened. The autolysis of the mur knockout strain was significantly lower and autolysis of the mur overexpressed strain was significantly higher compared with that of the wild type strain ljj-6. This result suggested that the mur gene played an important role in autolysis of L. bulgaricus. On the other hand, autolytic activity in a low degree was still observed in the mur knockout strain, which implied that other enzymes but autolysin encoded by mur were also involved in autolysis of L. bulgaricus.

Summary Milk protein concentrate was pretreated either by microwave irradiation or by ultrasound before initiation of 3-h enzymatic hydrolysis. The duration of pretreatment ranged from 1 to 8 min at a power level of 800 W, with the control not being subjected to any pretreatment, and five enzymes (Alcalase, Trypsin, Neutrase, Alkaline Protease and Flavourzyme) were employed. The effects of microwave and ultrasound pretreatments on the kinetics and degree of hydrolysis, protein solubility, bitterness and angiotensin-converting enzyme inhibitory activity were evaluated. Pretreatments increased the degree of hydrolysis and stabilised the solubility of the hydrolysates but could not significantly reduce bitterness of the hydrolysates The angiotensin-converting enzyme inhibitory activity of the hydrolysates were improved with 5-min ultrasound-pretreated Neutrase hydrolysates giving IC50 value of 0.23 mg mL−1. Kinetic parameters showed improved catalytic efficiencies. Pretreatments of milk protein concentrates with either microwave or ultrasound significantly improve the bioactivity and functional characteristics of the resulting hydrolysates.

The use of power ultrasound as a pretreatment to enhance the hydrolysis of milk protein concentrate (MPC) and subsequent angiotensin converting enzyme (ACE) inhibitory activity has been studied. Liquid chromatography was used to analyse peptide profiles of Neutrase-derived MPC hydrolysates after pretreatment at 0, 1, 3, 5 and 8 min at an ultrasound power level of 800 W.The peptide profiles indicated an increase in number of peptides when ultrasound pretreatment was applied. There was also an increase in the degree of hydrolysis of MPC hydrolysates. The profiles indicated that new small peptides in ultrasound pretreated samples (1-5 min) which were not present in the control samples and 8 min pretreated samples, could be responsible for increased ACE inhibitory activity. These small peptides were digested in the 8 min pretreated samples.Ultrasound pretreatment of MPC increases the ACE inhibitory activity of the hydrolysates because of the production of new small peptides. This can be used as a means to derive potent ACE inhibitory peptides at industrial scale in complex protein sources.

To establish a BN rat model for testing food allergenicity.BN rats of both sex and aged 4 and 8 weeks were exposed to different doses of ovalbumin (OVA) (1.00 mg, 0.10 mg and 0.01 mg) by intraperitoneal injection on the 1st, 5th and 10th day of the study and observed for 35 days. Blood samples were taken on the 28th and 35th day of the study from orbital plexus and serum specific IgE (OVA sIgE) were determined by ELISA.Compared with the control group, the concentrations of OVA sIgE of 8-week female BN rats on the 28th and 35th day were significantly increased when 1.00 mg and 0.10 mg OVA was applied (P0.05). The concentrations of OVA sIgE of 8-week male BN rats on the 28th day were significantly higher than that in the control group when 0.10 mg and 0.01 mg OVA was applied (P0.05). And the concentrations of OVA sIgE of 8-week male BN rats on the 35th day were significantly higher than that in the control group when 1.00 mg OVA was applied (P0.05). The concentrations of OVA sIgE of 4-week male BN rats on the 35th day were significantly higher than the control group when 1.00 mg OVA was applied (P0.05).Female rats were more sensitive than male rats to different doses of OVA administered intraperitoneally; 8-week rats were more sensitive than 4-week rats; the better dose of OVA for sensitizing BN rats was 0.10 mg or 1.00 mg. Therefore, an ideally sensitized animal model could be established by administering 8-week female BN rats with 0.10 mg or 1.00 mg OVA intraperitoneally in 35 days later.

Lactobacillus casei AST18 was screened as an antifungal lactic acid bacteria which we have reported before. In this research, the antifungal properties of cell-free culture filtrate (CCF) from L. casei AST18 were detected, and the antifungal compounds of CCF were prepared by ultrafiltration, and semi-preparative HPLC, and then determined by GC–MS. CCF was sensitive to pH and heat treatment but it was not affected by the treatment of trypsin and pepsin. Through the treatment of ultrafiltration and semi-preparative HPLC there were two parts of CCF which showed antifungal activities: part 1 and part 4. Lactic acid was identified as the main antifungal compound in part 1. In part 4, three small molecular substances were detected with GC–MS. The three potential antifungal substances were cyclo-(Leu-Pro), 2,6-diphenyl-piperidine, and 5,10-diethoxy-2,3,7,8-tetrahydro-1H,6H-dipyrrolo[1,2-a;1′,2′-d]pyrazine. The antifungal activity of L. casei AST18 was a synergistic effect of lactic acid and cyclopeptides.

It aims to study potential genotoxicity of almond skins.A bacterial reverse mutation assay was performed on S. typhimurium strains TA97, TA98, TA100, TA102, and TA1535 in the absence or presence of S-9 mixture at a dose range of 312.5 to 5 000 μg/plate. A micronucleus test and a mammalian bone marrow chromosome aberration tests were performed in Swiss Albino (CD-1) mice at doses of 625, 1 250, and 2 500 mg/kg bw used.Almond skins exerted no mutagenic activity in various bacterial strains of Salmonella typhimurium in either the absence or the presence of metabolic activation at all doses tested. Various doses of almond skins did not affect the proportions of immature to total erythrocytes, the number of micronuclei in the immature erythrocytes, or the number of structural and numerical chromosomal aberrations of Swiss albino mice.Almond skins are not genotoxic under the conditions of the in vitro bacterial reverse mutation assay and two in vivo tests - micronucleus test and mammalian bone marrow chromosome aberration test, which supports the safety of almond skins for dietary consumption.

To study the feasibility of C3H/HeJ mice as the food allergenicity rodent model and explore the appropriate period of two different routes of exposure and the change of helper T lymphocyte cell.Allergenic protein ovalbumin (OVA) was administered intraperitoneally or orally to female C3H/HeJ mice for 35 days. Blood samples were taken on the 14th, 28th and 35th days from the orbital plexus and sera were obtained to determine OVA specific IgE (OVA sIgE). Spleen samples were obtained on the 35th day to detect the mRNA expression of Th2-type cytokines IL-4 and Th1-type cytokines IFN-gamma by real-time RT-PCR.Compared with the control group, the concentration of OVA sIgE on 28th and 35th days were significantly increased in OVA group by gavage (P0.05). The concentration of OVA sIgE on 14th, 28th and 35th days were significantly higher than the control group when OVA was given intraperitoneally (P0.05). Compared with the control group, the mRNA expression of IL-4 of OVA group and OVA + Al(OH)3 group were significantly increased. The mRNA expression of IFN-gamma of OVA group and OVA + Al(OH) group were significantly lower than the control group.C3H/HeJ mice might be used as a rodent model for the assessment of allergenicity of food. The appropriate period is the 14th day for the route of intraperitoneal injection and the 28th day for oral gavage, respectively.

To compare the methods for developing immune-suppressed mice models induced by cyclophosphamide (CTX) with different dosages and ways.The mice were assigned to three groups; distilled water were given by gavage daily to the mice in control group; 60 mg/kg of CTX were given by gavage daily to the mice in CTX-1 group; and the mice in CTX-2 group were intraperitoneally injected (ip) with 200 mg/kg bw of CTX one day before the end of the experiment. The experiment lasted for 30 days.The body weight, spleen weight, the percentage of lymphocytes in peripheral blood, activities of natural killer cells (NK) and cytotoxic T lymphocytes (CTL) and HC50 in CTX-1 group were significantly lower than those in the control group (P0.05). The percentage of T lymphocytes in peripheral blood, the percentage of Th and Ts lymphocytes and Th/Ts ratio in CTX-2 group were significantly higher than those in the control group (P0.05). Other immunological indices in CTX-2 group were significantly lower than the control group (P0.05).A proper immunosuppressed animal model for the functional food evaluating system could be established by gavaging 60 mg/kg bw of CTX for 30 days or by one intraperitoneal injection (ip) of 200 mg/kg. But the former might be more fitted to establish the immunosuppressed model.

A suitable project manager has a very important promoting role to play in the smooth and successful implementation of the project. This paper attempts to set up a comprehensive evaluation model of project manager candidates and evaluation of the qualifications of the candidates for a construction project by using principles of fuzzy mathematics. Empirical research shows that fuzzy mathematical methods provide a new approach to selecting candidates for the project manager, based on a scientific, fair and reasonable evaluation of the suitability degree of a candidate, therefore, the main factors which constitute a project manager can be identified by using fuzzy comprehensive evaluation matrix, which contributes to cultivate and promote required talents.

To observe the potential effect of tea polyphenols and EGCG on cultured hypertrophic myocyte induced by Ang II.The study used cultured neonatal rat myocytes as a model to observe the potential effects of 10 microg/ml, 50 microg/ml and 100 microg/ml tea polyphenols and EGCG on hypertrophic myocyte induced by Ang II. We will measure the protein contents, the volume of myocyte, the numbers of fibrocasts.When compared to control group (untreated), the protein contents, the volume of myocytes, the numbers of fibrocasts in Ang II group increased. But all those in tea polyphenols and EGCG group decreased in a dose-dependent manner, when compared to Ang II group. However, the number of the myocyte cells in all groups has no significantly changed.Tea polyphenols and EGCG can effectively inhibit hypertrophy of cultured neonatal rat heart myocytes induced by Ang II.

Toxicological effect of 3-chloro-1,2-propanediol on rats were studied to provide scientific basis for assessing the effect of Chloropropanols on human health. 170 SD rats were divided randomly into 8 groups and the dose of 0, 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 16.0 mg/kg 3-chloro-1,2-propanediol were given to rats for 90 days by gavages per day, respectively. The weight and food efficiency, hematology and clinical chemistry, NAG, GGT and total protein in urine, sperm number, sperm survive rate and sperm aberration rate, the LDH and LDH-X activity in testis, rate of organ/weight and histopathological analysis were measured. The results showed that different dose of 3-chloro-1,2-propanediol did not has adverse effect on body weight, food efficiency, Hb, red cell, white cell, serum AST, ALT, creatine, ALP, LDH, total protein and albumin, urine GGT and total protein, LDH activity in testis. At the dose of 4.0, 8.0 and 16.0 mg/kg group, the activity of NAG in urine and the rate of kidney/weight was significantly increased compared with negative control groups; the pathological changes in kidney were observed in the same groups, and the sperm number was also significantly decreased. At the dose of 8.0 and 16.0 mg/kg group, sperm survive rate and the X-LDH activity were significantly decreased and pathological changes were also observed in testis and caudal epididymis. It was concluded that the activity of NAG in urine and sperm number is the sensitive biological effective marker. Because urine is a kind of convenient available biological material, NAG activity in urine is a good biological effective marker for assessing effect of Chloropropanols on health. If the NAG activity can be used as sensitive marker for assessment on human health need to be tested further in human study.