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The traditional Chinese medicine (TCM) You-Gui-Wan (YGW) has been used to treat asthma for hundreds of years.YGW is composed of 10 types of medicinal materials. However, the immune mechanism of YGW in asthma treatment has not been elucidated. Therefore, this study investigated asthma symptoms attenuated by YGW and the underlying immune regulatory mechanism.Intratracheal (i.t.) stimulation of BALB/c mice with Dermatophagoides pteronyssinus (Der p) was performed once per week (40 μL, 2.5 μg/μL). For six consecutive weeks, different doses of YGW (0.2 g/kg and 0.5 g/kg) were orally administered 30 min before stimulation with Der p. After the last stimulation, airway hyperreactivity, lung gene expression, and total immunoglobulin E (IgE) in blood were evaluated using a whole-body plethysmograph system, real-time PCR, and ELISA, respectively. In addition, DNP-IgE/DNP-BSA was added to stimulate mast cells (RBL-2H3), and YGW or various compound compositions (Trial) were added to RBL-2H3 cells for 30 min to evaluate the effects of the drug on mast cell degranulation and on gene expression. JMP 5.1 software was used to design and analyze YGW's critical compounds by which it inhibited ALOX-5 and HDC gene expression in RBL-2H3 cells.YGW significantly decreased serum total IgE levels and airway hyperresponsiveness in asthmatic mice. YGW also reduced the gene expression of IL-6, TNF-α, IL-4, IL-13, and COX-2 in the lungs of asthmatic mice and RBL-2H3 cells. YGW and the compound (Trial 21) present in YGW inhibited the gene expression of ALOX-5 and HDC in RBL-2H3 cells.The experimental results indicate that YGW exhibits anti-airway hyperresponsiveness and specific immunomodulatory effects. In addition, YGW synergistically inhibits ALOX-5 and HDC gene expression in mast cells through a combination of 21 compounds, including luteolin, quercetin, and β-carotene.

Objective The aim of this study was to investigate the effects of different amounts of wheat bran (WB) inclusion and postbiotics form by Saccharomyces cerevisiae and phytase co-fermented wheat bran (FWB) on the growth performance and health status of broilers. Methods Study randomly allocated a total of 300 male broilers to a control and 4 treatment groups (5% WB, 5% FWB, 10% WB, and 10% FWB inclusion, respectively) with each pen having 20 broilers and 3 pens per treatment. Results The WB does not contain enzymes, but there are 152.8, 549.2, 289.5, and 147.1 U/g dry matter xylanase, protease, cellulase and β-glucanase in FWB, respectively. Furthermore, FWB can decrease nitric oxide release of lipopolysaccharide stimulated chicken peripheral blood mononuclear cells by about two times. Results show that 10% FWB inclusion had significantly the highest weight gain (WG) at 1 to 21 d; 5% FWB had the lowest feed conversion rate at 22 to 35 d; 10% WB and 10% FWB inclusion have the highest villus height and Lactobacillus spp. number in caecum; and both 5% and 10% FWB can increase ash content in femurs. Compared to control group, all treatments increase mucin 2, and tight junction (TJ), such as occludin, claudin-1, zonula occludens-1, and mRNA expression in ileum by at least 5 folds. In chicken peripheral blood mononuclear cells, nicotinamide adenine dinucleotide phosphate-oxidase-1 mRNA expression decreases from 2 to 5 times, and glutamate-cysteine ligase catalytic subunit mRNA expression also increases in all treatment groups compared to control group. The mRNA expression of pro-inflammatory cytokines, including interleukin-6 (IL-6), nuclear factor-κB, and IL-1β, decreases in 5% and 10% FWB groups compared to control group. Conclusion To summarize, both WB and FWB inclusion in broilers diets increase TJ mRNA expression and anti-oxidation and anti-inflammation, but up to 10% FWB groups have better WG in different stages of broiler development.

BackgroundIntestinal inflammation is considered to be an important characteristic of ulcerative colitis (UC) and the current medical treatments for UC are usually proposed to suppress abnormal intestinal immune responses. Pulsatilla decoction (PD), a traditional Chinese medicine, is frequently used in UC treatments in Asian countries; however, the mechanism of the action of PD remains unclear. In the present study, the mechanism of the action of PD was elucidated in the dextran sulfate sodium (DSS)-induced colitis mouse model, a model to mimic UC.MethodsMurine colitis was evaluated by comparing the disease activity index score. The intestinal inflammation was examined by histology analyses. The leukocyte infiltration in the colonic tissues was examined by immunohistochemistry analyses. The cytokines level in colonic tissues was examined by Multi-Plex immunoassay. The epithelial proliferation was evaluated by histological analyses. Immunofluorescence double staining was used to examine the expression of MMP-7 in the immune cells.ResultsIn the DSS-induced colitis mouse model, administration of PD attenuated the intestinal inflammation, with a marked decrease in colonic infiltration of innate immune cells. Immunohistochemical analyses further showed that matrix metalloproteinase-7 (MMP-7) expressed by the infiltrating leukocytes, including neutrophils and macrophages was inhibited by PD treatment. PD increases the cytokine level of IL-6 in colonic tissues.ConclusionPD suppresses intestinal inflammation, with a marked decrease in colonic infiltration of innate immune cells, through decreasing MMP-7 expression.

Objective: Wheat bran (WB) was co-fermented with Aspergillus oryzae and phytase (Phy) to determine whether co-fermentation improve WB phosphorus and fiber utilization in Isa-brown layers.Methods: A total of 112 Isa brown layer were randomly divided into 7 treatments with 8 replicates per a treatment and 2 hens per a replicate. The treatments included basal diet (control), basal diet supplemented with 250 unit/kg Phy (control+Phy), diet with 10% WB (10% WB), diet with 5% WB and 250 unit/kg Phy (5% WB+Phy) diet with 10% WB and 250 unit/kg Phy (10% WB+Phy), diet with 5% fermented WB supplemented with molasses and phy (PCFWH) and 125 unit/kg Phy (5% PCFWH), and diet with 10% PCFWH (10% PCFWH). The intestinal microbial population, intestinal morphology, serum antioxidant enzyme activities, and excreta phosphorus content were assessed.Results: In PCFWH, spore counts, protease activity, xylanase activity, and ferulic acid were 8.50 log/g dry matter (DM), 190 unit/g DM, 120 unit/g DM, and 127 μg/g, respectively. Xylobiose and xylotriose were released in PCFWH, while they were not detectable in WB. Antioxidant capacity was also enhanced in PCFWH compared to WB. The 10% WB+Phy and 10% PCFWH groups produced higher egg mass, but hens fed 5% WB+Phy had the lowest amount of feed intake. Eggs from 10% PCFWH had better eggshell weight, eggshell strength, and eggshell thickness. Birds fed with 10% PCFWH also had higher serum superoxide dismutase and catalase activities. Compare to control, 10% PCFWH significantly reduced excreta phosphorus content.Conclusion: Diet inclusion of 10% PCFWH improved egg quality, antioxidant status, and excreta phosphorus content of laying hens.

This study explored the potential therapeutic efficacy of GSYJ in attenuating asthma symptom severity and aimed to determine the immunomodulatory mechanism of GSYJ. A mouse model of chronic asthma induced by repeated Dermatophagoides pteronyssinus (Der p) challenge was established. In addition, 30 minutes before Der p challenge, the mice were orally administered GSYJ (1 g/kg). The mice were sacrificed to evaluate inflammatory cell infiltration, collagen deposition in the lung, total IgE in serum, and expression profiles of various cytokines in bronchoalveolar lavage fluid (BALF) and various genes in lung tissue. Furthermore, 30 minutes after the addition of GSYJ to RAW264.7 cell cultures, 100 ng/ml LPS was added to evaluate the effect of the drug on the LPS-induced expression of genes, proteins, and transcription factors. GSYJ may regulate transcription factors (cJUN/IRF3/NF-κB) to decrease the expression of IL-1β, IL-6, RANTES, and iNOS in macrophages and affect the IL-12, IFN-γ, IL-5, and IL-6 levels in the BALF of mice to relieve asthma symptoms, such as inflammatory cell infiltration, hyperresponsiveness, and increased serum total IgE levels. Therefore, GSYJ has the potential to be developed into a drug treatment for chronic asthma.

Objective: The aim of this study was to investigate the effects of different amounts of wheat bran (WB) inclusion and postbiotics form by Saccharomyces cerevisiae and phytase cofermented wheat bran (FWB) on the growth performance and health status of broilers. Methods: Study randomly allocated a total of 300 male broilers to a control and 4 treatment groups (5% WB, 5% FWB, 10% WB, and 10% FWB inclusion, respectively) with each pen having 20 broilers and 3 pens per treatment. Results: The WB does not contain enzymes, but there are 152.8, 549.2, 289.5, and 147.1 U/g dry matter xylanase, protease, cellulase and β-glucanase in FWB, respectively. Furthermore, FWB can decrease nitric oxide release of lipopolysaccharide stimulated chicken peripheral blood mononuclear cells by about two times. Results show that 10% FWB inclusion had significantly the highest weight gain (WG) at 1 to 21 d; 5% FWB had the lowest feed conversion rate at 22 to 35 d; 10% WB and 10% FWB inclusion have the highest villus height and Lactobacillus spp. number in caecum; and both 5% and 10% FWB can increase ash content in femurs. Compared to control group, all treatments increase mucin 2, and tight junction (TJ), such as occludin, claudin-1, zonula occludens-1, and mRNA expression in ileum by at least 5 folds. In chicken peripheral blood mononuclear cells, nicotinamide adenine dinucleotide phosphate-oxidase-1 mRNA expression decreases from 2 to 5 times, and glutamate-cysteine ligase catalytic subunit mRNA expression also increases in all treatment groups compared to control group. The mRNA expression of pro-inflammatory cytokines, including interleukin-6 (IL-6), nuclear factor-κB, and IL-1β, decreases in 5% and 10% FWB groups compared to control group. Conclusion: To summarize, both WB and FWB inclusion in broilers diets increase TJ mRNA expression and anti-oxidation and anti-inflammation, but up to 10% FWB groups have better WG in different stages of broiler development.

Objective: This study compared the catechin composition of different tea byproducts and investigated the effects of dietary supplementation with green tea byproducts on the accumulation of abdominal fat, the modulation of lipid metabolism, and the inflammatory response in red feather native chickens.Methods: Bioactive compounds were detected, and in vitro anti-obesity capacity analyzed via 3T3-L1 preadipocytes. In animal experiments, 320 one-day-old red feather native chickens were divided into 4 treatment groups: control, basal diet supplemented with 0.5% Jinxuan byproduct (JBP), basal diet supplemented with 1% JBP, or basal diet supplemented with 5×106 colony-forming unit (CFU)/kg Bacillus amyloliquefaciens+5×106 CFU/kg Saccharomyces cerevisiae (BA+SC). Growth performance, serum characteristics, carcass characteristics, and the mRNA expression of selected genes were measured.Results: This study compared several cultivars of tea, but Jinxuan showed the highest levels of the anti-obesity compound epigallocatechin gallate. 3T3-L1 preadipocytes treated with Jinxuan extract significantly reduced lipid accumulation. There were no significant differences in growth performance, serum characteristics, or carcass characteristics among the groups. However, in the 0.5% JBP group, mRNA expression of fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) were significantly decreased. In the 1% JBP group, FAS, ACC and peroxisome proliferator-activated receptor γ levels were significantly decreased. Moreover, inflammation-related mRNA expression levels were decreased by the addition of JBP.Conclusion: JBP contained abundant catechins and related bioactive compounds, which reduced lipid accumulation in 3T3-L1 preadipocytes, however there was no significant reduction in abdominal fat. This may be due to a lack of active anti-obesity compounds or because the major changes in fat metabolism were not in the abdomen. Nonetheless, lipogenesis-related and inflammation-related mRNA expression were reduced in the 1% JBP group. In addition, dietary supplementation with tea byproducts could reduce the massive amount of byproducts created during tea production and modulate lipid metabolism and the inflammatory response in chickens.

Objective: This study was investigated the effects of dietary supplementation of Antrodia cinnamomea fermented product on modulation of antioxidation, anti-inflammation, and lipid metabolism in broilers.Methods: Functional compounds and in vitro antioxidant capacity were detected in wheat bran (WB) solid-state fermented by Antrodia cinnamomea for 16 days (FAC). In animal experiment, 400 d-old broiler chickens were allotted into 5 groups fed control diet, and control diet replaced with 5% WB, 10% WB, 5% FAC, and 10% FAC respectively. Growth performance, intestinal microflora, serum antioxidant enzymes and fatty acid profiles in pectoral superficial muscle were measured.Results: Pretreatment with hot water extracted fermented product significantly reduced chicken peripheral blood mononuclear cells death induced by lipopolysaccharide and 2,2′-Azobis(2-amidinopropane) dihydrochloride. Birds received 5% and 10% FAC had higher weight gain than WB groups. Cecal coliform and lactic acid bacteria were diminished and increased respectively while diet replaced with FAC. For FAC supplemented groups, superoxide dismutase (SOD) activity increased at 35 days only, with catalase elevated at 21 and 35 day. Regarding serum lipid parameters, 10% FAC replacement significantly reduced triglyceride and low-density lipoprotein level in chickens. For fatty acid composition in pectoral superficial muscle of 35-d-old chickens, 5% and 10% FAC inclusion had birds with significantly lower saturated fatty acids as compared with 10% WB group. Birds on the 5% FAC diet had a higher degree of unsaturation, followed by 10% FAC, control, 5% WB, and 10% WB.Conclusion: In conclusion, desirable intestinal microflora in chickens obtaining FAC may be attributed to the functional metabolites detected in final fermented product. Moreover, antioxidant effects observed in FAC were plausibly exerted in terms of improved antioxidant enzymes activities, increased unsaturated degree of fatty acids in chicken muscle and better weight gain in FAC inclusion groups, indicating that FAC possesses promising favorable mechanisms worthy to be developed.

Objective: This study was conducted to fathom the underlying mechanisms of nutrition intervention and redox sensitive transcription factors regulated by Antrodia cinnamomea fermented product (FAC) dietary supplementation in broiler chickens.Methods: Four hundreds d-old broilers (41±0.5 g/bird) assigned to 5 groups were examined after consuming control diet, or control diet replaced with 5% wheat bran (WB), 10% WB, 5% FAC, and 10% FAC. Liver mRNA expression of antioxidant, inflammatory and lipid metabolism pathways were analyzed. Prostaglandin E2 (PGE2) concentration in each group were tested in the chicken peripheral blood mononuclear cells (cPBMCs) of 35-d old broilers to represent the stress level of the chickens. Furthermore, these cells were stimulated with 2,2′-Azobis(2-amidinopropane) dihydrochloride (AAPH) and lipopolysaccharide (LPS) to evaluate the cell stress tolerance by measuring cell viability and oxidative species.Results: Heme oxygenase-1, glutathione S-transferase, glutamate-cysteine ligase, catalytic subunit, and superoxide dismutase, and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) that regulates the above antioxidant genes were all up-regulated significantly in FAC groups. Reactive oxygen species modulator protein 1 and NADPH oxygenase 1 were both rather down-regulated in 10% FAC group as comparison with two WB groups. Despite expressing higher level than control group, birds receiving diet containing FAC had significantly lower expression level in nuclear factor-kappa B (NF-κB) and other genes (inducible nitric oxide synthase, tumor necrosis factor-α, interleukin-1β, nucleotide-binding domain, leucine-richcontaining family, pyrin domain-containing-3, and cyclooxygenase 2) involving in inflammatory pathways. Additionally, except for 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase that showed relatively higher in both groups, the WB, lipoprotein lipase, Acetyl-CoA carboxylase, fatty acid synthase, fatty acid binding protein, fatty acid desaturase 2 and peroxisome proliferator-activated receptor alpha genes were expressed at higher levels in 10% FAC group. In support of above results, promoted Nrf2 and inhibited NF-κB nuclear translocation in chicken liver were found in FAC containing groups. H2O2 and NO levels induced by LPS and AAPH in cPBMCs were compromised in FAC containing diet. In 35-d-old birds, PGE2 production in cPBMCs was also suppressed by the FAC diet.Conclusion: FAC may promote Nrf2 antioxidant pathway and positively regulate lipid metabolism, both are potential inhibitor of NF-κB inflammatory pathway.

Background Dengue is endemic in over 100 countries and is an important public health problem worldwide. Dengue fever is not endemic in Taiwan; the importation of dengue viruses from neighboring countries via close commercial links and air travel is considered to be the cause of local outbreaks. Therefore, efforts toward disease control have focused on preventing the importation of dengue into Taiwan. In this study, we investigated the relationships between the numbers of imported and indigenous dengue cases to test the validity of this strategy. Methods Data on cases of dengue fever that occurred between 2013 and 2018 were obtained from the surveillance systems of the Taiwan Center for Disease Control and Kaohsiung City Health Department. Standard epidemiological data, including the monthly numbers of indigenous and imported cases of dengue, were calculated. Potential associations between the numbers of indigenous and imported cases were investigated using correlation analyses. Results We identified a possible relationship between the period of disease concealment and the number of imported dengue cases, which resulted in epidemics of indigenous dengue fever within local communities. Further analysis of confirmed cases during previous epidemics in Kaohsiung City found that the risk of indigenous dengue fever may be related to the likelihood that patients with imported dengue fever will stay within local communities. Conclusion Given the correlations found between imported and indigenous cases of dengue fever, as well as the relationship between the disease concealment period and the risk of indigenous dengue fever, prevention of disease importation and efficient identification of dengue cases within high-risk communities remain the major priorities for disease control.

This study evaluated the antioxidant capacity of Ricinus communis L. (RC) leaves and powder when used as a feed additive for laying hens. Results showed that the total phenolic content of the aqueous leaf extract of Ricinus communis L. (RCE) was 48.39 mg gallic acid equivalent (GAE) per gram dry weight (DW). The flavonoid content was 9.76 mg quercetin dihydrate equivalent (QE)/g DW. Ferrous chelating activity was approximately 56.2% with an RCE concentration of 1 mg/mL; the highest chelating activity was 91.2% with 4 mg/mL extract. The reducing power of 1 mg/mL RC was 1.17 times better than 1 mg/mL butylated hydroxytoluene (BHT). The Trolox equivalent antioxidant capacity (TEAC) value of 12.5 mg/mL RCE was equivalent to 3.09 mg/mL Trolox. RCE (10 mg/mL) had a lipid oxidative inhibition capacity of 35.3%. A total of 80 ISA brown laying hens at twenty-nine weeks of age were randomly allocated into the control or 1 of 3 treatment groups; the latter received 0.5%, 1% or 2% of RC, respectively, for 12 weeks. Results showed that the RC supplementation improved the feed conversion rate and 0.5% RC generated the best results. Additionally, the egg yolk score was significantly increased in all RC-supplemented groups. Moreover, there was no significant difference in serum characteristics between the treatment groups. Serum antioxidant enzyme activity showed that superoxide dismutase (SOD) activity increased in the RC-supplemented groups relative to the control but was not significantly different. mRNA expression levels of the antioxidant regulatory genes GCLC, GST, HO-1, SOD1, and SOD2 were significantly increased with 2% RC supplementation. In summary, RC is a suitable feed additive for laying hens and the addition of 0.5% RC leaf powder resulted in the greatest benefits.

This study investigated the effects of using mushroom waste compost as the residue medium for Pleurotus eryngii planting, which was used as a feed replacement, its consequent influence on broiler chickens’ intestinal microbiota, anti-inflammatory responses, and anti-oxidative status was likewise studied. A total of 240 male broilers were used and allocated to four treatment groups: the basal diet—control group (corn–soybean), 5% replacement of a soybean meal via PWMC (Pennisetum purpureum Schum No. 2 waste mushroom compost), 5% replacement of a soybean meal via FPW (Saccharomyces cerevisiae fermented PWMC), 5% replacement of a soybean meal via PP (Pennisetum purpureum Schum No. 2). Each treatment had three replicates and 20 birds per pen. The levels of glutathione peroxidase and superoxide dismutase mRNA as well as protein increased in the liver and serum in chickens, respectively, mRNA levels of inflammation-related genes were also suppressed 2 to 10 times in all treatments as compared to those in the control group. The tight junction and mucin were enhanced 2 to 10 times in all treatment groups as compared to those in the control, especially in the PWMC group. Nevertheless, the appetite-related mRNA levels were increased in the PWMC and FPW groups by at least two times. In ileum and cecum, the Firmicutes/Bacteroidetes ratios in broilers were decreased in the PWMC, FPW, and PP groups. The Lactobacillaceae in the ileum were increased mainly in the PWMC and control groups. Overall, high-fiber feeds (PWMC, FPW, and PP) could enhance the broilers’ health by improving their antioxidant capacities and decreasing their inflammatory response as compared to the control. Based on the results, a 5% replacement of the soybean meal via PWMC is recommended in the broiler chickens’ diet.

Ethnopharmacological relevance In Asia, Jin Gui Shen Qi Wan (JGSQW) has been used for hundreds of years to treat asthma. Aim of the study The traditional Chinese medicine JGSQW is composed of Rehmannia glutinosa, Dioscorea opposita, Cornus officinalis, Poria cocos, Paeonia suffruticosa, Alisma orientalis, Aconitum carmichaelii and Cinnamomum cassia. However, the immunological mechanism underlying the effect of JGSQW treatment on asthma remains unclear. This study examined whether JGSQW has the potential to reduce asthma symptoms in mice with chronic asthma induced by recurrent Dermatophagoides pteronyssinus (Der p) stimulation, as well as its immunoregulatory mechanisms. Materials and methods The airways of BALB/c mice were stimulated with Der p (i.t.) once per week (50 μL, 1 mg/mL) for 6 consecutive weeks, and the mice were fed JGSQW (1 g/kg) 30 min prior to the Der p stimulation. Three days after the last stimulation, the mice were sacrificed to evaluate the airway remodelling, infiltration of inflammatory cells, lung histological features, and total IgE in the blood. Additionally, after A549 cells were treated with JGSQW, loganin, or paeoniflorin for 30 min, 10 ng/mL IL-1β was added to stimulate the A549 cells to evaluate the effect of the medicine on the ICAM-1 gene expression after IL-1β stimulation. Results JGSQW significantly reduced the Der p-induced infiltration of inflammatory cells into airways and decreased the total IgE and Der p-specific IgG1 in serum. Collagen assays and histopathological examinations showed that JGSQW reduced lung airway remodelling. Additionally, an electrophoretic mobility shift assay and immunohistochemical staining verified that JGSQW inhibited the NF-kB expression in airway epithelial cell nuclei. JGSQW, loganin, and paeoniflorin inhibited the ICAM-1 gene expression caused by the IL-1β stimulation of A549 cells, and loganin and paeoniflorin had the maximum inhibitory effect when mixed according to the combination of doses in JGSQW. Conclusion These results indicated that in the chronic asthma mouse model, JGSQW inhibits the infiltration of inflammatory cells into the airways and airway remodelling and exhibits specific immunoregulatory effects. JGSQW with certain doses of loganin and paeoniflorin inhibited ICAM-1 gene expression in epithelial cells.

Advanced biofuels possess superior characteristics to serve for gasoline substitutes. In this study, a whole cell biocatalysis system was employed for production of short-chain alcohols from corresponding fatty acids. To do so, Escherichia coli strain was equipped with a biocatalytic pathway consisting of endogenous atoDA and Clostridium acetobutylicum adhE2. The strain was further reprogrammed to improve its biocatalytic activity by direction the glycolytic flux to acetyl-CoA and recycling acetate. The production of 1-propanol and n-pentanol were exemplified with the engineered strain. By substrate (glucose and propionate) feeding, the strain enabled production of 5.4 g/L 1-propanol with productivity reaching 0.15 g/L/h. In addition, the strain with a heavy inoculum was implemented for the n-pentanol production from n-pentanoic acid. The production titer and productivity finally attained 4.3 g/L and 0.86 g/L/h, respectively. Overall, the result indicates that this developed system is useful and effective for biocatalytic production of short-chain alcohols.

IntroductionAllergic asthma is a worldwide health problem, and its etiology remains incompletely understood. Besides, as current therapies for allergic asthma mainly rely on administration of glucocorticoids and have many side effects, new therapy is needed. You-Gui-Wan (YGW), a traditional Chinese herbal remedy, has been used for boosting Yang, enhancing immunity and treating allergic asthma.ObjectivesThis study aims to explore the molecular changes during the development of allergic asthma and investigate the potential bio-signatures and the effect of YGW on house dust mite (HDM)-induced chronic allergic asthma in mice.MethodsDermatophagoides pteronyssinus (Der p), one of HDMs, was intratracheally administered once a week for a total of 7 treatments over 6 consecutive weeks to induce allergic asthma in mice. Serum metabolomics was analyzed by LC-QTOF-MS/MS. 16S rRNA-based microbiome profiling was used to analyze gut microbiota, and the correlation between metabolomic signatures and microbial community profiling was explored by Spearman correlation analysis.ResultsSerum metabolomic analysis revealed that 10 identified metabolites — acetylcarnitine, carnitine, hypoxanthine, tryptophan, phenylalanine, norleucine, isoleucine, betaine, methionine, and valine, were markedly elevated by Der p. These metabolites are mainly related to branch-chain amino acid (BCAA) metabolism, aromatic amino acid (AAA) biosynthesis, and phenylalanine metabolism. YGW administration reversed 7 of the 10 identified metabolites and chiefly affected BCAA metabolism. 16S DNA sequencing revealed that YGW profoundly changed Der p-induced gut microbiota composition. Multiple correlation analysis indicated 10 selected metabolites have a good correlation with gut microbiota.ConclusionDer p induced BCAA metabolic deviation in allergic asthma mice, and YGW administration effectively ameliorated the AA metabolic disorder, and improved gut dysbiosis. This study paves the way towards the interactions of Der-p on microbiome and gut microbiota, and the effects of YGW treatment as well as provides a support for YGW administration with potential benefits for allergic asthma.

Additional file 1 Supplementary Fig. 1. Map showing the distance between the top/ bottom 5 countries from which Dengue was imported and Kaohsiung city. The analysis chart was created after analyzing all collected imported dengue fever data from 2013 to 2018 and referring to the dengue map constructed by the Taiwan CDC (https://cdcdengue.azurewebsites.net/Imported.aspx). The world map is publicly available via OpenStreetMap (https://www.openstreetmap.org/).

Antrodia camphorata mycelium is used in traditional Chinese medicine in Taiwan. The wild-type mycelium is rare and expensive, so a solid-state-cultured mycelium of A. camphorata (SCMAC) has been developed. Previous studies have found SCMAC to have anti-inflammatory effects. However, the immunomodulatory effects of SCMAC and of its active phytosterol compounds EK100 and 9A on asthma remain unknown. In this study, BALB/c mice were repeatedly exposed to Dermatogoides pteronyssinus (Der p) at 1-week intervals and were orally administered crude SCMAC extract before the Der p challenge. The mice were sacrificed 72 h after the last challenge to examine the airway remodeling, inflammation, and expression profiles of cytokines and various genes. Then, 30-µg/mL Der p-stimulated MH-S cells with 9A or EK100 were collected for real-time PCR analysis, and the effects of 9A and EK100 on macrophages were evaluated. The crude extract reduced Der p-induced airway hyperresponsiveness, total serum immunoglobulin E levels, and recruitment of inflammatory cells to the bronchoalveolar lavage fluid through cytokine downregulation and Th1/Th2/Th17 response modulation. Additionally, 9A and EK100 inhibited IL-1β and IL-6 expression in alveolar macrophages. These results indicate that the pharmacologically active compounds in a crude SCMAC extract exert synergistic effects on multiple targets to relieve asthma symptoms.

Antrodia cinnamomea, a precious and unique medical fungus existing exclusively in Taiwan, exhibits antioxidant and immunomodulatory properties. This study was conducted to evaluate the beneficial effects of A. cinnamomea powder (ACP) and to further illuminate its underlying antioxidant and immunomodulation molecular mechanisms in broilers. The functional compounds of ACP—crude triterpenoids, crude polysaccharides, and total phenolic content—were assayed, respectively. Two-hundred-forty one-day-old broilers (Ross 308) were assigned to 4 treatment groups receiving dietary supplementation with ACP at 0, 0.1, 0.2, and 0.4% for 35 days. Each group had 4 replicate pens, with 15 birds per pen. During 1 to 21- and 22 to 35-day periods, chickens on ACP-supplemented diet demonstrated increased body weight gain, compared to those on the control diet, resulting in increased weight gain throughout the entire experimental period with an increased tendency in feed consumption yet no significant difference in FCR. Blood antioxidant potentiality, superoxide dismutase (SOD), increased in birds fed the supplemented diet at both 21 and 35 d, accompanied by higher catalase (CAT) activity at 21 days. In vivo peripheral blood mononuclear cells (PBMC) exposed to lipopolysaccharide (LPS) and 2,2′-Azobis(2-amidinopropane) dihydrochloride (AAPH) capability showed that the diminished cell viability caused by both challenge factors was improved in ACP-supplemented groups. Antioxidant genes dominated by Nrf2 genes, such as HO-1 and GCLC, were up-regulated in 35-day-old birds. Inflammatory-related genes, such as IL-1β and IL-6, ruled mainly by NF-κB, were rather down-regulated by 0.2% ACP addition at 21 and 35 days. Protein expression of Nrf2 and NF-κB in the liver supported the mRNA results, demonstrating that all ACP-supplemented groups showed significantly higher Nrf2 expression, whereas the NF-κB was inhibited. In conclusion, preferable microbial balance may putatively indicate the improvement of immunomodulatory-related capacity by ACP. Furthermore, ACP could induce the Nrf2-dependent pathway and decrease the NF-κB-dominated inflammatory signaling pathway. Antioxidant and immune capacity in terms of antioxidant enzymes and cell tolerance also was elevated by ACP. Concomitantly, body weight increasing with ACP supplementation as compared to the corresponding control group further implied the promising effects exerted by ACP.

Glucose from plant cellulose and glycerol from the waste stream of the biodiesel production process are two most abundant and renewable carbon sources. n-Butanol is an alternative fuel of potential and its production by microbes which utilize the two carbons appears to be industrially incentive on the ground of sustainability and economy. However, the hierarchical regulation of glucose dictates Escherichia coli to prefer utilization of glucose over others. This physiological behavior of the cell prolongs the fermentation process and eventually reduces productivity. In this study, a single strain capable of co-utilizing glucose and glycerol was developed by metabolic engineering. Meanwhile, a dual-culture system was also designed by construction of a glucose-selecting and a glycerol-selecting strain. As a consequence, both approaches result in the strains for effective co-utilization of glucose and glycerol. In particular, the single strain enabled production of 6.2 g/L n-butanol, which leads to the conversion yield and productivity accounting for 76.5% of the theoretical and 0.17 g/L/h, respectively. It indicates a promise of the developed technology platform for microbial production of n-butanol from the glucose–glycerol mixture.

The effect of soybean peptides from fermented soybean meal on the intestinal immunity and tight junction of broilers was assessed. Roughly, two-stage fermented soybean meal prepared with Bv and Lb (FSBMB+L), which has nearly three times higher soluble peptides than soybean meal (SBM), and reduced galacto-oligosaccharide (GOS) content and allergen protein. The one-stage fermented by Bv (FSBMB) has the highest soluble peptides, while commercial lactic acid bacteria (FSBML) has the highest Lactic acid bacteria count, these were used to compare the differences in the process. Ross308 broilers (n = 320) were divided into four groups: SBM diet and a diet replaced with 6% FSBMB+L, FSBMB, or FSBML. The growth performance was recorded during the experiment, and six birds (35-day-old) per group were euthanized. Analysis of their jejunum and ileum showed that the fermented soybean meal significantly improved the villus height in the jejunum (p &lt, 0.05) and reduced the crypt hyperplasia. The FSBMB group had the highest reducing crypt depth, however, the FSBMB+L group had the highest villus height/crypt depth in the ileum (p &lt, 0.05). In the jejunum, the relative mRNA of CLDN-1 and Occludin increased 2-fold in the treatments, and ZO-1 mRNA increased 1.5 times in FSBML and FSBMB+L (p &lt, 0.05). Furthermore, the level of NF-κB and IL-6 mRNAs in FSBML increased, respectively, by 4 and 2.5 times. While FSBMB, along with FSBMB+L, had a 1.5-fold increase in the mRNA of IL-10, that of NF-κB increased 2-fold. FSBMB+L and FSBMB singly led to a 2- and 3-fold increase in IL-6 mRNA, respectively (p &lt, 0.05). FSBMB and FSBMB+L can also upregulate MUC2 in the jejunum (p &lt, 0.05). In short, using the soybean peptides from two-stage fermented soybean meal can ameliorate the negative factors of SBM and effectively regulate immune expression and intestinal repair, which will help broilers maintain intestinal integrity.

East Asians are reportedly at high risk of anticoagulant-related bleeding; therefore, some physicians prefer to prescribe low-dose direct oral anticoagulants (DOACs). Little is known about the therapeutic effectiveness and safety of off-label reduced-dose apixaban in East Asians with nonvalvular atrial fibrillation (AF). We aimed to investigate the effectiveness and safety of off-label reduced-dose apixaban in Taiwanese patients with nonvalvular AF.This retrospective cohort study enrolled 1073 patients with nonvalvular AF who took apixaban between July 2014 and October 2018 from 4 medical centers in southern Taiwan. The primary outcomes included thromboembolic events (stroke/transient ischemic attack or systemic embolism), major bleeding, and all-cause mortality.Among all patients, 826 (77%) patients were classified as the "per-label adequate-dose" treatment group (i.e., consistent with the Food and Drug Administration label recommendations) while 247 (23%) patients were the "off-label reduced-dose" treatment group. The mean follow-up period was 17.5 ± 13 months. The "off-label reduced-dose" group did not have a lower major bleeding rate than the "per-label adequate-dose" group (4.8% vs 3.8%, adjusted hazard ratio [HR] 1.20, 95% confidence interval [CI] 0.69-2.09), but had a nonsignificantly higher incidence of thromboembolic events (4.23% vs 3.05%, adjusted HR: 1.29, 95% CI: 0.71-2.34).An off-label reduced-dose apixaban treatment strategy may not provide incremental benefits or safety for Taiwanese patients with nonvalvular AF.

Herein we report an effective and simple preparation method of substituted azoxybenzenes by reductive dimerization of nitrosobenzenes. This procedure requires no additional catalyst/reagent and can be applied to substrates with a wide range of substitution patterns.

Background Despite limited evidence, postoperative prophylactic antibiotics are often used in the setting of permanent pacemaker implantation or replacement. The aim of this study is to investigate the efficacy of postoperative antibiotics. Hypothesis Postoperative prophylactic antibiotics may be not clinically useful. Methods We recruited 367 consecutive patients undergoing permanent pacemaker implantation or generator replacement at a tertiary referral center. Baseline demographics, clinical characteristics, and procedure information were collected, and all patients received preoperative prophylactic antibiotics. Postoperative prophylactic antibiotics were administered at the discretion of the treating physician, and all patients were seen in follow-up every 3 to 6 months for an average follow-up period of 16 months. The primary endpoint was device-related infection. Results A total of 110 patients were treated with preoperative antibiotics only (group 1), whereas 257 patients received both preoperative and postoperative antibiotics (group 2). After a mean follow-up period of 16 months, 1 patient in group 1 (0.9%) and 4 patients in group 2 (1.5%) experienced a device-related infection. There was no significant difference in the rate of infection between the 2 groups (P = 0.624). In the univariate analysis, only the age (60 ± 11 vs 75 ± 12 years, P < 0.001) was significantly different between the infected and noninfected groups. In the multivariate analysis, younger age was an independent risk factor for infective complications (odds ratio = 1.08, P = 0.016). Conclusions Patients treated with preoperative and postoperative antibiotics had a similar rate of infection as those treated with preoperative antibiotics alone. Further studies are needed to confirm these preliminary findings.

Abstract Background. Dengue is endemic in over 100 countries and is an important public health problem worldwide. Dengue is not considered endemic in Taiwan however, with importation of dengue viruses from neighboring countries via close commercial links and air travel believed to be the cause of local outbreaks. Disease control efforts have therefore focused on preventing the importation of dengue into Taiwan. Here, we investigate the relationships between numbers of imported and indigenous dengue cases to test the validity of this strategy. Methods. Dengue-fever case data from between 2013 and 2018 was obtained from the surveillance systems of the Taiwan Center for Disease Control and Kaohsiung City Health department. Standard epidemiological data, including the monthly numbers of indigenous and imported dengue cases, was calculated. Potential associations between the number of indigenous and imported cases were investigated using correlation analyses. Results. We identified a possible relationship between the period of disease concealment and the number of reported imported dengue cases which resulted in indigenous dengue-fever epidemics within local communities. Further analysis of confirmed dengue cases during previous dengue-fever epidemics in Kaohsiung City found that the risk of indigenous dengue-fever may be related to the likelihood of patients suffering from imported cases of dengue-fever staying within local communities. Conclusion. Given the correlations found between imported and indigenous dengue-fever cases, as well as the relationship between disease concealment period and risk of indigenous dengue-fever, the major priorities for disease control remain prevention of disease importation and efficient identification of dengue cases within high-risk communities.

Ethnopharmacological relevance In Asia, Qi-Wei-Du-Qi-Wan (QWDQW) is a traditional Chinese medicine that has been used to treat chest tightness, cough, shortness of breath, night sweats, frequent urination and asthma. QWDQW is recorded in Yi Zong Yi Ren Pian (Medical Physician's Compilation), which was written by Yang Cheng Liu during the Qing Dynasty. Aim of the study The traditional Chinese medicine QWDQW is composed of 7 ingredients and has been used in the treatment of asthma in Asia for hundreds of years. However, the mechanism through which QWDQW affects the immune system in the treatment of asthma is not known. Therefore, this study aimed to investigate whether QWDQW alleviates asthmatic symptoms in mice with chronic asthma induced by repeated stimulation with Dermatophagoides pteronyssinus (Der p) and to explore the underlying immune modulatory mechanism. Materials and methods BALB/c mice were stimulated intratracheally (i.t.) with Der p (40 μl, 2.5 μg/μl) once weekly for 6 weeks. Thirty minutes prior to Der p stimulation, the mice were treated with QWDQW (0.5 g/kg and 0.17 g/kg) orally. Three days after the last stimulation, the mice were sacrificed, and infiltration of inflammatory cells, lung histological characteristics, gene expression of lung and serum total IgE were assessed. In other experiments, RBL-2H3 cells were stimulated with DNP-IgE/DNP-BSA and then treated with QWDQW, quercetin, β-carotene, luteolin or a mixture of the three chemicals (Mix13) for 30 min, and the effects of the drugs on RBL-2H3 cell degranulation after DNP stimulation were determined. Results QWDQW significantly reduced Der p-induced airway hyperreactivity (AHR) and decreased total serum IgE and Der p-specific IgE levels. Histopathological examination showed that QWDQW reduced inflammatory cell infiltration and sputum secretion from goblet cells in the lungs. Gene expression analysis indicated that QWDQW reduced overproduction of IL-12、IFN-γ、IL-13、IL-4、RNATES、Eotaxin and MCP-1in lung. Additionally, QWDQW and Mix13 suppressed DNP induced RBL-2H3 degranulation, and the effect was maximal when quercetin, β-carotene and luteolin were administered together. Conclusion These results indicate that QWDQW plays a role in suppressing excessive airway reaction and in specific immune modulation in a mouse model of chronic asthma and that QWDQW suppresses mast cell degranulation at defined doses of quercetin, β-carotene and luteolin.

Chinese herbal remedies have long been used for enhancing immunity and treating asthma. However, the evidence-based efficacy remains to be supported. This study aimed to explore the potential bio-signatures in allergic asthma and the effect of You-Gui-Wan (YGW), a traditional Chinese herbal prescription, on dust mite-induced mouse allergic asthma. Extract of Dermatophagoides pteronyssinus (Der p), a dust mite, was intratracheally administered to induce allergic asthma in mice. Serum metabolomic and 16S rRNA-based microbiome profiling were used to analyze untargeted metabolites with levels significantly changed and gut microbiota composition, respectively. Results indicated that 10 metabolites (acetylcarnitine, carnitine, hypoxanthine, tryptophan, phenylalanine, norleucine, isoleucine, betaine, methionine, and valine), mainly associated with branched-chain amino acid (BCAA) metabolism, aromatic amino acid (AAA) biosynthesis, and phenylalanine metabolism were markedly elevated after Der p treatment. YGW administration reversed the levels for 7 of the 10 identified metabolites, chiefly affecting BCAA metabolism. On 16S DNA sequencing, disordered Der p-induced gut microbiota was significantly alleviated by YGW. Multiple correlation analysis showed a good correlation between gut microbiota composition and levels of selected metabolites. Our study showed YGW administration effectively alleviated BCAA metabolic disorder and improved gut dysbiosis. This study provides support for YGW administration with benefits for allergic asthma.

Zebrafish are well recognized as an excellent vertebrate model which, in particular, facilitates the rapid investigation of drug effects on cancers. A prerequisite for this anti-cancer study appears to have a non-invasive and effecicve method for admininstration of drugs. In this study, we explored the potential of artificial oil bodies (AOBs) for the oral administration of a hydrophobic agent in adult zebrafish. A hydrophobic dye was employed for illustration, and AOBs were assembled with phospholipids, a storage protein, and an equal volume of olive oil and brine shrimp oil. Consequently, more than 90% of the dye was encapsulated in AOBs which exhibited a prolonged release profile for the dye cargo. The dye-loaded AOBs collected as an oil cake remained integral within 30 min in the aquatic solution while it was completely consumed by one zebrafish in a few seconds. As revealed by the fluorescence microscopy and frozen section, the fluorescence signal was detected in the zebrafish intestinal tract 2 h after the oral administration. The dye cargo was completely absorbed in 12 h and almost no trace was left in zebrafish feces. Overall, the AOBs system is biocompatible and shows promise in the oral administration of chemical entities for zebrafish.

Oral administration of Traditional Chinese Medicine (TCM) by patients is the common way to treat health problems. Zebrafish emerges as an excellent animal model for the pharmacology investigation. However, the oral delivery system of TCM in zebrafish has not been established so far. This issue was addressed by development of alginate microparticles for oral delivery of chuanxiong, a TCM that displays antifibrotic and antiproliferative effects on hepatocytes. The delivery microparticles were prepared from gelification of alginate containing various levels of chuanxiong. The chuanxiong-encapsulated alginate microparticles were characterized for their solubility, structure, encapsulation efficiency, the cargo release profile, and digestion in gastrointestinal tract of zebrafish. Encapsulation of chuanxiong resulted in more compact structure and the smaller size of microparticles. The release rate of chuanxiong increased for alginate microparticles carrying more chuanxiong in simulated intestinal fluid. This remarkable feature ensures the controlled release of encapsulated cargos in the gastrointestinal tract of zebrafish. Moreover, chuanxiong-loaded alginate microparticles were moved to the end of gastrointestinal tract after oral administration for 6 hr and excreted from the body after 16 hr. Therefore, our developed method for oral administration of TCM in zebrafish is useful for easy and rapid evaluation of the drug effect on disease.

It is unknown whether there has been any change in the causes of death for acute ST-segment elevation myocardial infarction (STEMI) in the era of aggressive reperfusion. We analyzed the direct causes of in-hospital death in patients with STEMI treated with primary percutaneous coronary intervention (PCI) in a tertiary referral center over the past 10 years.We retrospectively analyzed 878 STEMI patients treated with primary PCI in our hospital between January 2005 and December 2014. There were no significant changes in the age and sex of patients, but the prevalence of hypertension and smoking decreased. STEMI severity increased with more patients in Killip classification > 2. The number of out-ofhospital cardiac arrest events also increased over the 10 years. Symptom onset-to-door time did not change in the 10year study period. The care quality was improved with shorter door-to-balloon time for primary PCI and increased use of dual antiplatelet therapy. The all-cause in-hospital mortality was 9.1%, which did not vary over the 10 years. Multivariable analysis showed that Killip classification > 2 was the most important determinant of death. Cardiogenic shock was the major cause of cardiovascular death. There was an increase in non-cardiovascular causes of death in the most recent 3 years, with infection being a major problem.Despite improvement in care quality for STEMI, the in-hospital mortality did not decrease in this tertiary referral center over these 10 years due to increased disease severity and non-cardiovascular causes of death.

Background Information on the incidence of venous thromboembolism (VTE) following hip fractures in Asia is rare. This study will investigate the epidemiology of symptomatic VTE in Taiwanese patients experiencing hip fractures. Methods and results We used Taiwan's National Health Insurance Research Database to retrospectively identify patients (≧ 45 years) who experienced hip fractures from 1998 to 2007 and were followed up for 3 months after the discharge. Logistic regression analysis determined the independent risk factors of symptomatic VTE after the fractures. We identified 134,034 patients (mean age: 76.2 ± 9.7 years; female: 57.8%) who experienced hip fractures, 83.2% of whom underwent hip surgery. The overall pharmacological thromboprophylaxis rate was 2.7%. The mean length of stay was 11.3 ± 7.9 days. The 3-month cumulative incidence of symptomatic VTE was 77 events per 10,000 persons. Multivariate analysis showed that previous DVT, previous PE, varicose veins, cancer, heart failure, renal insufficiency, and older age were independent risk factors of developing VTE. Conclusions The incidence of symptomatic VTE after hip fractures is low in Taiwan. Patients rarely received pharmacological thromboprophylaxis following hip fractures. Universal thromboprophylaxis for patients experiencing hip fractures was not necessary in Taiwan, but it should be considered in high-risk populations.

Lung cancer is the most widespread disease and is frequently associated with a high level of epidermal growth factor receptor (EGFR). This study was thus conducted to provide a proof-of-concept approach for targeted therapy of lung cancer by development of nanoscale oil bodies (NOBs). This was carried out by fusion of anti-EGFR affibody (ZEGFR2) with oleosin (Ole), a structure protein of plant seed oils. The fusion protein (Ole-ZEGFR2) was produced in Escherichia coli. NOBs were spontaneously assembled from plant oil, phospholipids, and Ole-ZEGFR2. Consequently, Ole-ZEGFR2-based NOBs were selectively internalized by EGFR-positive lung cancer cells with an efficiency exceeding 90%. Furthermore, the hydrophobic anticancer drug, camptothecin (CPT), was encapsulated into Ole-ZEGFR2-based NOBs. The administration of the CPT formulation based on NOBs resulted in a strong antitumor activity both in vitro and in vivo.

This study was conducted to determine the effect of dietary supplement of bacterial lycopene (BL) produced by Escherichia coli on the egg quality and blood characteristics of laying quails. The antioxidant activity measurement showed that BL exhibited 100% 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging capacity at a concentration of 4.65 μg/ml, which was more effective than butylated hydroxytoluene (BHT) and commercial lycopene (CL). Moreover, seven dietary groups of laying quails consisting of 10 100-day-old quails (Coturnix coturnix japonica) each were fed with the basal diet supplemented with BL, CL or canthaxanthin (CA) for 4 weeks. Consequently, the triglyceride content of yolk was significantly lower in the group with BL and CL supplement. The serum malondialdehyde (MDA) level of the BL- and CA-supplemented groups at 18 mg/kg was lower than the control group. In conclusion, BL has a high antioxidant activity and is promising as a feed additive in the diet of laying quails.

Background Glycyrrhizin, silymarin, and ursodeoxycholic acid are widely used hepatoprotectants for the treatment of liver disorders, such as hepatitis C virus infection, primary biliary cirrhosis, and hepatocellular carcinoma. Purpose The gene expression profiles of HepG2 cells responsive to glycyrrhizin, silymarin, and ursodeoxycholic acid were analyzed in this study. Methods HepG2 cells were treated with 25 µM hepatoprotectants for 24 h. Gene expression profiles of hepatoprotectants-treated cells were analyzed by oligonucleotide microarray in triplicates. Nuclear factor-κB (NF-κB) activities were assessed by luciferase assay. Results Among a total of 30,968 genes, 252 genes were commonly regulated by glycyrrhizin, silymarin, and ursodeoxycholic acid. These compounds affected the expression of genes relevant various biological pathways, such as neurotransmission, and glucose and lipid metabolism. Genes involved in hepatocarcinogenesis, apoptosis, and anti-oxidative pathways were differentially regulated by all compounds. Moreover, interaction networks showed that NF-κB might play a central role in the regulation of gene expression. Further analysis revealed that these hepatoprotectants inhibited NF-κB activities in a dose-dependent manner. Conclusion Our data suggested that glycyrrhizin, silymarin, and ursodeoxycholic acid regulated the expression of genes relevant to apoptosis and oxidative stress in HepG2 cells. Moreover, the regulation by these hepatoprotectants might be relevant to the suppression of NF-κB activities.

Background The incidence of venous thromboembolism (VTE) in Asians is lower than in Caucasians, but the risk of VTE associated with hormone therapy (HT) in Taiwanese postmenopausal women has not been determined. Methods and results From Taiwan's National Health Insurance Research Database, we established matched cohorts (HT users and nonusers) of postmenopausal women aged ≥50 years between 1 January 1998 and 31 December 2008. We calculated the 2-year incidence of VTE in HT users and nonusers. HT users and nonusers were matched 1:1 based on propensity-score matching. Cox regression hazard model was used to identify risk factors of VTE. We initially identified 499,594 HT users and 424,963 nonusers. There were higher percentages of cancer and cardiovascular events among the HT nonusers. After matching, the VTE incidence was 4.4 vs. 2.6 per 10,000 patient-years (adjusted hazard ratio 1.796, 95% confidence interval 1.272-2.537) in HT users and nonusers, respectively. The Cox regression hazard model showed that HT use, older age, malignancy, heart failure, and recent major surgery were independent risk factors for VTE. Conclusions Although the incidence of VTE was very low among this cohort of Taiwanese postmenopausal women, oral HT was still associated with an increased risk of VTE. Therefore, physicians should be aware of other potential VTE risk factors when prescribing oral HT to postmenopausal women.

The microbial production of n-butanol using glucose and xylose, the major components of plant biomass, can provide a sustainable and renewable fuel as crude oil replacement. However, Escherichia coli prefers glucose to xylose as programmed by carbohydrate catabolite repression (CCR). In this study, a synthetic consortium consisting of two strains was developed by transforming the CCR-insensitive strain into a glucose-selective strain and a xylose-selective strain. Furthermore, the dual culture was reshaped by distribution of the synthetic pathway of n-butanol into two strains. Consequently, the co-culture system enabled effective co-utilization of both sugars and production of 5.2 g/L n-butanol at 30 h. The result leads to the conversion yield and productivity accounting for 63% of the theoretical yield and 0.17 g L-1 h-1, respectively. Overall, the technology platform as proposed is useful for production of other value-added chemicals, which require complicated pathways for their synthesis by microbial fermentation of a sugar mixture.

1. The study focused on antioxidant molecular targets of wheat bran fermented by white rot fungi (WRF) in poultry. After solid-state fermentation of wheat bran by WRF for 12 d, scanning electron microscopy found that the lignocellulose structure showed degradation and fragmentation. 2. A total of 300 1-d-old broilers were evenly divided by gender and randomly allocated into the following treatments: (1) maize-soybean meal (control group), (2) 10% of wheat bran replacing maize (10% WB group) or (3) 10% of fermented wheat bran replacing maize (10% FWB group). 3. The results indicated that the antioxidant gene expression, such as haem oxygenase-1 and glutathione-S-transferase of chicken peripheral blood mononuclear cells, of the 10% FWB group was significantly higher than that of the control group at d 35. For genes of Nicotinamide adenine dinucleotide phosphate oxygenase 1 and reactive oxygen species modulator protein 1, the expression of the 10% FWB group was lower than that of the control group at d 21 and 35. 4. In conclusion, wheat bran fermented by WRF could increase lignocellulolytic enzyme activities and the levels of active components that further regulate the expression of antioxidant molecular targets in poultry.

Objective— One potential mechanism through which obesity exerts adverse effects on the vascular system is by increasing aortic stiffness, a change known to be predictive of increased cardiovascular mortality. The aim of this study was to investigate the pathophysiology that links obesity to aortic stiffening. Approach and Results— Obese ( ob/ob ) mice were used to examine physical, morphological, and molecular changes in the aorta in response to obesity. ob/ob mice had increased aortic pulse wave velocity and tissue rigidity. ob/ob aorta exhibited decreases of lysyl oxidase (LOX) activity and cross-linked elastin, and increases of elastin fragmentation and elastolytic activity. The aortas of ob/ob mice were surrounded by a significant amount of proinflammatory and pro-oxidative perivascular adipose tissue. In vitro studies revealed that the conditioned medium from differentiated adipocytes or the perivascular adipose tissue of ob/ob mice attenuated LOX activity. Furthermore, inhibition of LOX in wild-type lean mice caused elastin fragmentation and induced a significant increase in pulse wave velocity. Finally, we found that obese humans had stiffer arteries and lower serum LOX levels than do normal-weight humans. Conclusion— Our results demonstrated that obesity resulted in aortic stiffening in both humans and mice, and established a causal relationship between LOX downregulation and aortic stiffening in obesity.

Background Right ventricular (RV) pacing is associated with left ventricular (LV) dysfunction. However, the effects of RV pacing at different sites on both LV and RV function have rarely been studied before. We want to determine whether different RV pacing sites differentially affect LV and RV deformation by using speckle tracking echocardiography (STE). Methods The subjects were 73 patients who had undergone dual-chamber permanent pacemaker implantation and did not have structural heart diseases. LV and RV global longitudinal strains (GLS) were measured using STE to determine subtle changes in LV function. Twenty-three patients without pacing after pacemaker implantation served as controls; 14 and 36 patients showed apical and septal pacing, respectively. Results There were no significant intergroup demographic differences. LV biplane ejection fractions in the septal- and apical-pacing groups were significantly lower than those in the controls. The GLSLV values were similar between the control and septal-pacing groups, but they were lower in the apical-pacing group. Multivariate analysis revealed that cumulative pacing loads and apical pacing were independent factors associated with lower GLSLV values. The GLSRV values were similar between the control and apical-pacing groups; however, they were lower in the septal-pacing group. Conclusion We concluded that patients with septal pacing have significantly higher GLSLV and more modest decreases in GLSRV values than patients with apical pacing. Thus, septal pacing may be not necessarily preferable in patients without significant heart disease undergoing dual-chamber permanent pacemaker implantation.