Effect of Protease Combined with Heat Treatment on the Volatile Composition and Aroma Quality in Liqueur Wine.

The aim of this paper was to compare the effects of two clarification methods, protease combined with heat treatment and bentonite, on the aroma quality of liqueur wines, and to identify and analyze the overall differences between the basic components and volatile aroma compounds of liqueur wines after the two treatments by chemical analysis, headspace-solid-phase microextraction-gas chromatography/mass spectrometry (HS-SPME-GC/MS), and orthogonal partial least squares discriminant analysis (OPLS-DA). The results showed that total acidity, volatile acidity and pH in liqueur wines after protease combined with heat treatment were not significantly different from those of the blank control, and the ability to remove proteins was equal to that of the bentonite treatment. A total of 58 volatile aroma compounds were detected by HS-SPME-GC/MS. Compared with the blank control group (44 species, total 108.705 mg/L), 52 (83.233 mg/L) and 50 (120.655 mg/L) aroma compounds were detected in the bentonite and protease combined with heat treatments, respectively. Compared with the control and bentonite treatment, the protease combined with heat treatment significantly increased the total content of aromatic compounds in liqueur wines, and the types and contents of olefins, furans and phenols were higher. Among them, the compounds with major contributions in the protease combined with heat treatment were ionone, ß-damascenone, 3-methyl-1-butanol, alpha-terpineol and limonene, which helped increase the content of terpenoids and enhance the floral and fruit aroma of the wine. Meanwhile, linalool, diethyl succinate, 2-methyl-3-heptanone, butanal diethyl acetal, hexanal and n-octanol were six compounds with high content of aromatic compounds unique to liqueur wines after protease combined with heat treatment. The sensory evaluation results were consistent with the results of aromatic compound detection, and the overall quality was better. The results may provide a reference for further exploration of protease-based clarifiers suitable for liqueur wines.

Thermographic evaluation of acupoints in lower limb region of individuals with osteoarthritis: A cross-sectional case-control study protocol.

PURPOSE: Acupuncture has been widely used in the treatment of knee osteoarthritis (KOA), but the selection of acupoints is indeterminate and lacks biological basis. The skin temperature of acupoints can reflect the state of local tissue and may be a potential factor for guiding acupoint selection. This study aims to compare the skin temperature of acupoints between KOA patients and the healthy population. STUDY DESIGN AND METHODS: This is a protocol for a cross-sectional case-control study with 170 KOA patients and 170 age- and gender-matched healthy individuals. Diagnosed patients aged 45 to 70 will be recruited in the KOA group. Participants in the healthy group will be matched with the KOA group based on mean age and gender distribution. Skin temperature of 11 acupoints (ST35, EX-LE5, GB33, GB34, EX-LE2, ST34, ST36, GB39, BL40, SP9, SP10) will be extracted from infrared thermography (IRT) images of the lower limbs. Other measurements will include demographic data (gender, age, ethnicity, education, height, weight, BMI) and disease-related data (numerical rating scale, pain sites, duration of pain, pain descriptors, pain activities). DISCUSSION: The results of this study will provide biological evidence for acupoint selection. This study is a precondition for follow-up studies, in which the value of optimized acupoint selection will be verified. TRIAL REGISTRATION: ChiCTR2200058867.

Prophylactic Rivaroxaban Therapy for Left Ventricular Thrombus After Anterior ST-Segment Elevation Myocardial Infarction.

OBJECTIVES: The aim of this study was to investigate the effects of rivaroxaban on left ventricle thromboprophylaxis in patients with anterior ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Anterior STEMI is associated with an increased risk of left ventricular thrombus (LVT) formation. The contemporary role of prophylactic rivaroxaban therapy remains unclear. METHODS: We randomly assigned 279 patients with anterior STEMI who had undergone primary percutaneous coronary intervention to receive, in a 1:1 ratio, low-dose rivaroxaban (2.5 mg twice daily for 30 days) and dual antiplatelet therapy (DAPT) or only DAPT. The primary efficacy outcome was the LVT formation within 30 days. Net clinical adverse events were assessed at 30 days and 180 days, including all-cause mortality, LVT, systemic embolism, rehospitalization for cardiovascular events, and bleeding. RESULTS: The addition of low-dose rivaroxaban to DAPT reduced LVT formation within 30 days compared with only DAPT (0.7% vs 8.6%; HR: 0.08; 95% CI: 0.01-0.62; P = 0.015; P < 0.001 for superiority). Net clinical adverse events were lower within 30 days in the rivaroxaban group versus those in the only DAPT group and remained relatively low throughout the follow-up period. There were no significant differences in bleeding events between the 2 groups in 30 days and 180 days. However, 1 case of intracranial hemorrhage (major bleeding) occurred in the rivaroxaban group within 30 days. CONCLUSIONS: Our results supported that the short-duration addition of low-dose rivaroxaban to DAPT could prevent LVT formation in patients with anterior STEMI following primary percutaneous coronary intervention. A larger multiple-institution study is necessary to determine the generalizability.

Determination of the Interaction and Pharmacological Modulation of MCHR1 Signaling by the C-Terminus of MRAP2 Protein.

Melanin concentrating hormone (MCH), an orexigenic neuropeptide, is primarily secreted by the hypothalamus and acts on its receptor, the melanin-concentrating hormone receptor 1 (MCHR1), to regulate appetite and energy homeostasis. The Melanocortin Receptor Accessory Protein 2 (MRAP2), a small single transmembrane protein broadly expressed in multiple tissues, has been defined as a vital endocrine modulator of five melanocortin receptors (MC1R-MC5R) and several other GPCRs in the regulation of central neuronal activities and peripheral energy balance. Here, we demonstrated the interaction between MRAP2 and MCHR1 by immunoprecipitation and bimolecular fluorescent assay and found that MRAP2 could inhibit MCHR1 signaling in vitro. A series of functional truncations of different regions further identified that the C-terminal domains of MRAP2 protein were required for the pharmacological modulation of intracellular Ca2+ coupled cascades and membrane transport. These findings elucidated the broad regulatory profile of MRAP2 protein in the central nervous system and may provide implications for the modulation of central MCHR1 function in vivo.

Betulinic acid improves nonalcoholic fatty liver disease through YY1/FAS signaling pathway.

The increasing prevalence of nonalcoholic fatty liver disease (NAFLD) worldwide indicates the urgent need to develop novel and effective treatment strategies. Betulinic acid (BA), a naturally occurring plant-derived pentacyclic triterpenoid, has an outstanding effect in improving metabolism. However, the pharmacological action and mechanism of BA in NAFLD remain unclear. Here, we show that BA-treated high-fat diet mice and methionine-choline deficient diet-fed mice are resistant to hepatic steatosis when compared with vehicle-treated mice. BA alleviates fatty acid synthesis, fibrosis, and inflammation and promotes fatty acid oxidation. Meanwhile, fatty acid synthase (FAS) expression and activity are markedly inhibited with BA treatment both in vitro and in vivo. Moreover, BA inhibits FAS expression through transcriptional suppression of Yin Yang 1 (YY1), leading to retard hepatocytes triglyceride accumulation. Collectively, BA protects hepatocytes from abnormal lipid deposition in NAFLD through YY1/FAS pathway. Our findings establish a novel role of BA in representing a possible therapeutic strategy to reverse NAFLD.

Association Between Copper, Zinc, Iron, and Selenium Intakes and TC/HDL-C Ratio in US Adults.

The trace minerals zinc, copper, iron, and selenium are essential micronutrients, and because of their antioxidant activity, they are hypothesized to improve cardiovascular health. However, their associations with different risk levels for cardiovascular diseases are less clear. Data from the National Health and Nutrition Examination Survey 2007-2014 were used. In this study, the ratio of total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) was used as a risk marker for cardiovascular disease, and a ratio ≥ 5 was considered to indicate high risk. A total of 7597 adults (3673 men and 3924 women) were included, and 15.9% of the participants had a high risk of cardiovascular disease. Using quantile regression analysis, we found the negative correlation between zinc, copper, iron, and selenium intakes and TC/HDL-C. The effects of copper and zinc were enhanced with increasing quantiles of risk levels. In addition, the difference in the associations of the trace minerals was sex-dependent. The correlation between iron and cardiovascular risk in males was stronger than those in females, while that of copper was weaker than that in females. Moreover, a significant nonlinear relationship between selenium and the TC/HDL-C ratio was only found in females, and this relationship was U-shaped. Our findings suggest that among healthy adults in the US, zinc, copper, iron, and selenium intakes are inversely associated with cardiovascular disease risk, and the effect is enhanced with increasing quantiles of risk levels, with magnitudes differing by sex. Therefore, trace minerals may have the ability to prevent cardiovascular disease.

Protective effects of protopanaxatriol on acute liver injury induced by concanavalin A.

The purpose of this study was to explore the protective effect of protopanaxatriol (PPT) on acute liver injury induced by concanavalin A (ConA). In this study, mice were randomly separated into four groups. The first group received PBS (i.v.). The second group was given PPT (50 mg/kg body weight, i.p.) for 3 days before PBS (i.v.) injection. The third group received ConA (15 mg/kg body weight, i.v.). The fourth group was administered PPT (50 mg/kg body weight, i.p.) for 3 days before ConA (i.v.) injection. The serum levels of ALT and AST were detected after 20 h of ConA injection. The pathological changes of liver were observed by H/E staining. The expression of inflammatory factors was measured by ELISA and qRTPCR, and the changes of the signaling pathway were detected by western blot. Histopathological changes and blood transaminase elevation indicated significant liver injury after ConA injection. However, PPT pretreatment obviously reversed these changes. The ELISA and qRT-PCR results indicated that PPT preconditioning significantly inhibited the production of inflammatory factors. In addition, this inhibitory effect of PPT was mainly mediated by regulation of the nuclear factor-κB (NF-κB) signaling pathway. The active ingredient of ginseng, PPT, exerts an obvious protective effect on acute liver injury caused by ConA through inhibiting the inflammatory response.

Association of multiple mineral and vitamin B group intake with blood glucose using quantile regression analysis: NHANES 2007-2014.

BACKGROUND: Hyperglycaemia and diabetes have become major public health problems worldwide. There is increasing evidence that minerals and the vitamin B group might play specific roles in hyperglycaemia and the pathogenesis and progression of diabetes or metabolic complications. OBJECTIVES: The main aim of this study is to investigate the effect of mineral and vitamin B group supplementation on the blood glucose levels of different populations. DESIGN: This was a cross-sectional study. Data from the National Health and Nutrition Examination Survey (NHANES) 2007-2014 were used in this study. A total of 8,322 participants (4,169 men and 4,153 women) were included in the study. Quantile regression (QR) was performed to identify the influence of mineral and vitamin B group intake on the level of fasting plasma glucose (FPG) in individuals in different quantiles of FPG. RESULTS: After adjusting for age, income, education, race, smoking, and alcohol consumption, FPG had a negative association with folic acid in individuals with normal or high FPG, with calcium in individuals with normal FPG, and with magnesium in males. FPG was negatively associated with folic acid and calcium in individuals with normal FPG, and magnesium in most of the quantiles for females. DISCUSSION: Hyperglycaemia and diabetes are currently becoming popular research topics. However, little is known about how the whole continuum of blood glucose is associated with commonly researched nutrient supplementation in terms of hyperglycaemia and diabetes. CONCLUSIONS: The intake of calcium, folic acid and magnesium was negatively associated with blood glucose levels in individuals in different quantiles of FPG. Appropriate prevention and treatment strategies should be developed for people with different blood glucose levels.

Integrating multi-omics analyses of Nonomuraea dietziae to reveal the role of soybean oil in [(4'-OH)MeLeu]4-CsA overproduction.

BACKGROUND: Nonomuraea dietziae is a promising microorganism to mediate the region-specific monooxygenation reaction of cyclosporine A (CsA). The main product [(4'-OH)MeLeu]4-CsA possesses high anti-HIV/HCV and hair growth-stimulating activities while avoiding the immunosuppressive effect of CsA. However, the low conversion efficiency restricts the clinical application. In this study, the production of [(4'-OH)MeLeu]4-CsA was greatly improved by 55.6% from 182.8 to 284.4 mg/L when supplementing soybean oil into the production medium, which represented the highest production of [(4'-OH)MeLeu]4-CsA so far. RESULTS: To investigate the effect of soybean oil on CsA conversion, some other plant oils (corn oil and peanut oil) and the major hydrolysates of soybean oil were fed into the production medium, respectively. The results demonstrated that the plant oils, rather than the hydrolysates, could significantly improve the [(4'-OH)MeLeu]4-CsA production, suggesting that soybean oil might not play its role in the lipid metabolic pathway. To further unveil the mechanism of [(4'-OH)MeLeu]4-CsA overproduction under the soybean oil condition, a proteomic analysis based on the two-dimensional gel electrophoresis coupled with MALDI TOF/TOF mass spectrometry was implemented. The results showed that central carbon metabolism, genetic information processing and energy metabolism were significantly up-regulated under the soybean oil condition. Moreover, the gas chromatography-mass spectrometry-based metabolomic analysis indicated that soybean oil had a great effect on amino acid metabolism and tricarboxylic acid cycle. In addition, the transcription levels of cytochrome P450 hydroxylase (CYP) genes for CsA conversion were determined by RT-qPCR and the results showed that most of the CYP genes were up-regulated under the soybean oil condition. CONCLUSIONS: These findings indicate that soybean oil could strengthen the primary metabolism and the CYP system to enhance the mycelium growth and the monooxygenation reaction, respectively, and it will be a guidance for the further metabolic engineering of this strain.

Comparative proteomic and metabolomic analysis of Streptomyces tsukubaensis reveals the metabolic mechanism of FK506 overproduction by feeding soybean oil.

FK506 (tacrolimus) is a 23-membered polyketide macrolide that possesses powerful immunosuppressant activity. In this study, feeding soybean oil into the fermentation culture of Streptomyces tsukubaensis improved FK506 production by 88.8%. To decipher the overproduction mechanism, comparative proteomic and metabolomic analysis was carried out. A total of 72 protein spots with differential expression in the two-dimensional gel electrophoresis (2-DE) were identified by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry (MALDI-TOF/TOF-MS), and 66 intracellular metabolites were measured by gas chromatography-mass spectrometer (GC-MS). The analysis of proteome and metabolome indicated that feeding soybean oil as a supplementary carbon source could not only strengthen the FK506 precursor metabolism and energy metabolism but also tune the pathways related to transcriptional regulation, translation, and stress response, suggesting a better intracellular metabolic environment for the synthesis of FK506. Based on these analyses, 20 key metabolites and precursors of FK506 were supplemented into the soybean oil medium. Among them, lysine, citric acid, shikimic acid, and malonic acid performed excellently for promoting the FK506 production and biomass. Especially, the addition of malonic acid achieved the highest FK506 production, which was 1.56-fold of that in soybean oil medium and 3.05-fold of that in initial medium. This report represented the first comprehensive study on the comparative proteomics and metabolomics applied in S. tsukubaensis, and it would be a rational guidance to further strengthen the FK506 production.

Berberine activates thermogenesis in white and brown adipose tissue.

Obesity develops when energy intake exceeds energy expenditure. Promoting brown adipose tissue formation and function increases energy expenditure and hence may counteract obesity. Berberine (BBR) is a compound derived from the Chinese medicinal plant Coptis chinensis. Here we show that BBR increases energy expenditure, limits weight gain, improves cold tolerance and enhances brown adipose tissue (BAT) activity in obese db/db mice. BBR markedly induces the development of brown-like adipocytes in inguinal, but not epididymal adipose depots. BBR also increases expression of UCP1 and other thermogenic genes in white and BAT and primary adipocytes via a mechanism involving AMPK and PGC-1α. BBR treatment also inhibits AMPK activity in the hypothalamus, but genetic activation of AMPK in the ventromedial nucleus of the hypothalamus does not prevent BBR-induced weight loss and activation of the thermogenic programme. Our findings establish a role for BBR in regulating organismal energy balance, which may have potential therapeutic implications for the treatment of obesity.

[Molecular identification of Hibiscus syriacus and its adulterants using ITS2 barcode].

OBJECTIVE: To identify Hibiscus syriacus and its adulterants using DNA barcoding technique. METHODS: Nine samples of five species were PCR amplified and sequenced, and twelve samples were downloaded from the GenBank. The intra-specific and interspecific K2P distances were calculated, and neighbor-joining( NJ) tree was constructed by MEGA 5.0. RESULTS: The results showed the intra-specific genetic distances of Hibiscus syriacus were ranged from 0.009 to 0.056, which were far lower than inter-specific genetic distances between Hibiscus syriacus and its adulterants (0.236 - 0.301). Variable sites within Hibiscus syriacus ranged from 2 to 9 which were far less than the adulterants (45 - 52); Different samples of Hibiscus syriacus were gathered together and could be distinguished from its adulterants by NJ tree. CONCLUSION: ITS2 can discriminate Hibiscus syriacus from its adulterants correctly. The ITS2 region is an efficient barcode for authentication of Hibiscus syriacus and its adulterants.

Optimization of synthesis, characterization and cytotoxic activity of Seleno-Capparis spionosa L. polysaccharide.

In this study, an experiment was designed to optimize the synthesis of seleno-Capparis spionosa L. polysaccharide (Se-CSPS) by response surface methodology. Three independent variables (reaction time, reaction temperature and ratio of Na(2)SeO(3) to CSPS) were tested. Furthermore, the thermal stability, particle size, shape and cytotoxic activity of Se-CSPS in vitro were investigated. The optimum reaction conditions were obtained shown as follows: reaction time 7.5 h, reaction temperature 71 °C, and ratio of Na(2)SeO(3) to CSPS 0.9 g/g. Under these conditions, the Se content in Se-CSPS reached 5.547 mg/g, which was close to the predicted value (5.518 mg/g) by the model. The thermal stability, particle size and shape of Se-CSPS were significantly different from those of CSPS. Additionally, a MTT assay indicated that the Se-CSPS could inhibit the proliferation of human gastric cancer SGC-7901 cells in a dose-dependent manner.

Optimizing the extraction of anti-tumor polysaccharides from the fruit of Capparis spionosa L. by response surface methodology.

Capparis spionosa L. is a traditional medicinal plant in China and central Asia. In this study, an experiment was designed to investigate the optimization of the extraction of anti-tumor polysaccharides from the fruit of Capparis spionosa L. (CSPS) by response surface methodology (RSM). Four independent variables (extraction temperature, extraction time, ratio of water to sample and extraction cycles) were explored. Meanwhile, the in vivo anti-tumor activity of CSPS was investigated. The results showed that the experimental data could be fitted to a second-order polynomial equation using multiple regression analysis. The optimum extraction conditions were as follows: extraction temperature 92 °C, extraction time 140 min, ratio of water to sample 26 mL/g, and three extraction cycle. Under these conditions, the yield of polysaccharides reached 13.01%, which was comparable to the predicted yield (12.94%, p > 0.05). This indicated that the model was adequate for the extraction process. Additionally, CSPS could prolong the survival time of H22 bearing mice in vivo. The anti-tumor activities of CSPS were dose-dependent.

Phase-controllable synthesis of nanosized nickel phosphides and comparison of photocatalytic degradation ability.

In this paper, we employed a facile hydrothermal route to successfully synthesize nanosized nickel phosphide particles with controlled phases via selecting different surfactants at different temperatures and times. The phases of the as-obtained products were determined by X-ray powder diffraction (XRD) patterns and Rietveld refinement of XRD data. The morphologies of the products were characterized by (high resolution) transmission electron microscopy (HR/TEM) and field emission scanning electron microscopy (FESEM). Experiments indicated that pure Ni2P phase could be prepared when nontoxic red phosphorus and nickel dichloride were used as starting materials in the presence of polyvinylpyrrolidone (PVP, 30 K), sodium dodecylbenzene sulfonate (SDBS), cetyltrimethylammonium bromide (CTAB) or polyethylene glycol 10000 (PEG-10000) at 160 °C for 10 h. When acrylamide (AM) was selected as the surfactant, however, pure Ni12P5 phase could be prepared by prolonging the reaction time to 20 h at 160 °C, or enhancing the reaction temperature to 180 °C for 10 h. Furthermore, the experiments indicated that the pure Ni2P phase possessed a stronger photocatalytic degradation ability than the pure Ni12P5 phase.

Methylmercury, total mercury and total selenium in four common freshwater fish species from Ya-Er Lake, China.

Snakehead fish (Ophiocephalus argus cantor), silver carp (Hypophthalmichthys molitrtix), crucian carp (Carassius carassius), and common carp (Cyprinus carpio) are four common freshwater fish species in China. In this study, the level of methylmercury (MeHg), total mercury (T-Hg), and total selenium (T-Se) in muscle samples of these four fish species from Ya-Er Lake, China, were analyzed using atomic fluorescence spectrometry coupled with high-performance liquid chromatography, and inductively coupled plasma mass spectrometry. The concentrations of MeHg in all the fish species were significantly correlated with those of T-Hg. Higher T-Hg and MeHg concentrations had accumulated in the snakehead fish, which is a strongly predatory fish, than in the other three species. The concentration ratios of MeHg and T-Hg in the muscles of these four fish species were almost equal. Conversely, there was negative correlation between the concentrations of T-Hg and T-Se, which implies that there is a competition between these two elements with respect to bioaccumulation. It is noteworthy that of all the muscle samples tested, the level of T-Hg exceeded the maximum allowable limit in fish [0.4 mg kg(-1) (w/w) recommended by the World Health Organization] in 38.46% of those of the silver carp, 18.18% of those of the crucian carp, and 100% of those of snakehead fish. These results show that the consumption of contaminated fish is a potential threat to human health and that necessary preventive measures to safeguard public health should be emphasized.