This study was conducted to evaluate the effects of grape seed extract (GSE) on growth performance, immunity, antioxidant capacity, relative organ weight, jejunum morphology, ileal microflora, and ...meat quality in Pekin ducks. A total of 1,500 female 1-day-old Pekin ducklings (52.0 ± 0.2 g) were blocked based on body weight (BW) and randomly allocated into 3 treatments with 10 replicates of 50 birds each. The experiment lasted for 6 wk, and dietary treatments included corn-soybean meal-based diet supplemented with 0, 0.01, and 0.02% GSE. The supplementation of GSE increased (P < 0.05) body weight gain (BWG) and final BW linearly but decreased (P < 0.05) feed-to-gain ratio (F/G) linearly during day (D) 22 to 42 and the entire experiment. The inclusion of GSE increased (P < 0.05) serum superoxide dismutase, glutathione peroxidase, total antioxidative capacity, catalase, complement4, immunoglobin G, interleukin-2, and interferon-γ linearly but decreased (P < 0.05) serum malondialdehyde linearly. The relative weight of carcass, breast meat, and spleen in GSE treatments was increased (P < 0.05) linearly, whereas the relative weight of abdominal fat was decreased linearly (P < 0.05). Birds fed GSE1 and GSE2 diets had lower (P < 0.05) cook loss, 2-thiobarbituric acid reactive substances, and drip loss on day 3 and 5 linearly but higher (P < 0.05) pH24h and water-holding capacity. The addition of GSE decreased (P < 0.05) jejunum crypt depth and ileal Escherichia coli counts linearly but increased (P < 0.05) jejunum villus height: crypt depth ratio and ileal Lactobacilli linearly. Taken together, the inclusion of GSE increased final BW and BWG, decreased F/G during day 22 to 42 and day 1 to 42, partially improved antioxidant activities, immunity, meat quality, and gut health in Pekin ducks.
One-day-old Ross 308 male broiler chicks were used to investigate the additive effect during growth of Bacillus subtilis B2A derived from soil samples on productivity, organ weight, intestinal ...Salmonella microflora, and breast meat quality. Five hundred seventy-six birds (46 ± 0.5 g) were fed 3 different levels of B. subtilis B2A (1.1 × 104, 1.0 × 105, and 1.0 × 106 cfu), in a basal diet based on corn-soybean meal, for 28 d. In the current study, feed intake and feed conversion during 1 to 28 d showed significant improvement as dietary B. subtilis B2A increased from 1.1 × 104 to 1.0 × 106 cfu (linear, P < 0.05). All blood parameters, such as white blood cells, red blood cells, and lymphocyte and haptoglobin concentrations, were not influenced by B. subtilis B2A added into the diet; however, the weights of the bursa of Fabricius were significantly increased linearly in B. subtilis B2A-fed groups (P < 0.05). Bacillus subtilis B2A supplementation was associated with reduced intestinal Salmonella burden (linear and quadratic, P < 0.05). Breast meat pH and color were not affected by B. subtilis B2A, but 1 d drip loss was decreased (linear, P < 0.05). Our observations suggest that B. subtilis B2A benefits productivity and reduces Salmonella in broilers.
We optimally localized isolated fluorescent beads and molecules imaged as diffraction-limited spots, determined the orientation of molecules and present reliable formulas for the precision of various ...localization methods. Both theory and experimental data showed that unweighted least-squares fitting of a Gaussian squanders one-third of the available information, a popular formula for its precision exaggerates beyond Fisher's information limit, and weighted least-squares may do worse, whereas maximum-likelihood fitting is practically optimal.
We aimed to evaluate the long-term clinical outcomes and prognostic factors of symptomatic intracranial unruptured vertebrobasilar artery dissection (siu-VBD).
A total of 191 patients (M:F = 127:64; ...median age, 46 years) with siu-VBD were treated between January 2001 and December 2008. Presentations, treatments, outcomes, and prognostic factors were retrospectively analyzed.
Clinical manifestations were ischemic symptoms with headache (n = 97) or without headache (n = 13) and headache without ischemic symptoms (n = 81). Forty-six patients (24.1%) underwent endovascular treatment. The remaining 145 patients (75.9%) were medically treated with anticoagulants (n = 49), antiplatelets (n = 48), or analgesics alone (n = 48). Clinical follow-up data were available in 178 patients (102 ischemic and 76 nonischemic) at 15 to 102 months (mean, 46 months). None of the siu-VBD hemorrhaged. All 76 patients without ischemic presentation had favorable outcomes (modified Rankin Scale, 0-1). Of the 102 patients with ischemic presentation, outcomes were favorable in 92 and unfavorable in 10 patients. Four patients died; 3 died of causes unrelated to VBD, and one died as a result of basilar artery (BA) dissection. Old age (odds ratio OR 1.099; 95% confidence interval CI 1.103-1.204; p = 0.042) and BA involvement (OR 11.886; 95% CI 1.416-99.794; p = 0.023) were independent predictors of unfavorable outcomes in siu-VBD with ischemic presentation.
Clinical outcomes for siu-VBD were favorable in all patients without ischemic symptoms and in most patients with ischemic presentation. None of the siu-VBD caused subarachnoid hemorrhage. Old age and BA involvement were independent predictors of unfavorable outcome in siu-VBD with ischemic presentation.
Bacillus subtilis C-3102 has been used as a direct-fed microbial or probiotic product since 1986 to improve production performance in broilers worldwide. This study was conducted to determine and ...confirm the effect of B. subtilis C-3102 spore supplementation to feed on growth performance, nutrient digestibility, carcass quality, blood profiles, noxious gas emission, and intestinal and excreta microflora in broilers. A total of 816 one-day-old male Ross 308 broilers (46.06 ± 0.67 g) were used in a 5-wk study with Calsporin, B. subtilis final product (1.0 × 10(9) cfu/g of B. subtilis). Broilers were randomly allotted to 1 of 3 dietary treatments consisting of 16 replicate cages with 17 broilers each: I) CON (control, basal diet), II) BS300 (CON + 300 mg of B. subtilis/kg of feed), and III) BS600 (CON + 600 mg of B. subtilis/kg of feed). Regarding probiotic effect, B. subtilis significantly increased Lactobacillus counts in the cecum, ileal, and excreta, and reduced Escherichia coli counts in the cecum and excreta, compared with CON. In addition, supplementation also tended to reduce Clostridium perfringens counts in the large intestine and excreta, while linearly reducing Salmonella counts in the cecum, ileal, large intestine, and excreta, compared with CON. Regarding growth performance, B. subtilis enhanced ADG in the starter and overall experimental periods, without any effects on feed intake compared with CON. Consequently, feed conversion ratio in the grower-finisher and overall experimental periods decreased significantly. The inclusion of B. subtilis improved the digestibility of DM and gross energy, as well as reducing ammonia emission, compared with CON. No significant difference in breast muscle color, water holding capacity, and drip loss, and relative organ weights, as well as in white blood cells, red blood cells, lymphocyte counts, and IgG amount, were observed. Overall, B. subtilis C-1302 is capable of providing a probiotic effect leading to improved growth performance and feed efficiency, due to the manipulation of intestinal microflora, with minimal side effects in broilers.
Cancer immunotherapy has revolutionized the treatment landscape in medical oncology, but its efficacy has been variable across patients. Biomarkers to predict such differential response to ...immunotherapy include cytotoxic T lymphocyte infiltration, tumor mutational burden, and microsatellite instability. A growing number of studies also suggest that baseline tumor burden, or tumor size, predicts response to immunotherapy. In this review, we discuss the changes in immune profile and therapeutic responses that occur with increasing tumor size. We also overview therapeutic approaches to reduce tumor burden and favorably modulate the immune microenvironment of larger tumors.
Bacterial dysbiosis accompanies carcinogenesis in malignancies such as colon and liver cancer, and has recently been implicated in the pathogenesis of pancreatic ductal adenocarcinoma (PDA)
. ...However, the mycobiome has not been clearly implicated in tumorigenesis. Here we show that fungi migrate from the gut lumen to the pancreas, and that this is implicated in the pathogenesis of PDA. PDA tumours in humans and mouse models of this cancer displayed an increase in fungi of about 3,000-fold compared to normal pancreatic tissue. The composition of the mycobiome of PDA tumours was distinct from that of the gut or normal pancreas on the basis of alpha- and beta-diversity indices. Specifically, the fungal community that infiltrated PDA tumours was markedly enriched for Malassezia spp. in both mice and humans. Ablation of the mycobiome was protective against tumour growth in slowly progressive and invasive models of PDA, and repopulation with a Malassezia species-but not species in the genera Candida, Saccharomyces or Aspergillus-accelerated oncogenesis. We also discovered that ligation of mannose-binding lectin (MBL), which binds to glycans of the fungal wall to activate the complement cascade, was required for oncogenic progression, whereas deletion of MBL or C3 in the extratumoral compartment-or knockdown of C3aR in tumour cells-were both protective against tumour growth. In addition, reprogramming of the mycobiome did not alter the progression of PDA in Mbl- (also known as Mbl2) or C3-deficient mice. Collectively, our work shows that pathogenic fungi promote PDA by driving the complement cascade through the activation of MBL.
Gut microbes are linked to host metabolism, but specific mechanisms remain to be uncovered. Ceramides, a type of sphingolipid (SL), have been implicated in the development of a range of metabolic ...disorders from insulin resistance (IR) to hepatic steatosis. SLs are obtained from the diet and generated by de novo synthesis in mammalian tissues. Another potential, but unexplored, source of mammalian SLs is production by Bacteroidetes, the dominant phylum of the gut microbiome. Genomes of Bacteroides spp. and their relatives encode serine palmitoyltransfease (SPT), allowing them to produce SLs. Here, we explore the contribution of SL-production by gut Bacteroides to host SL homeostasis. In human cell culture, bacterial SLs are processed by host SL-metabolic pathways. In mouse models, Bacteroides-derived lipids transfer to host epithelial tissue and the hepatic portal vein. Administration of B. thetaiotaomicron to mice, but not an SPT-deficient strain, reduces de novo SL production and increases liver ceramides. These results indicate that gut-derived bacterial SLs affect host lipid metabolism.
This experiment was conducted to evaluate the effect of diets with different energy and emulsifier (Lipidol, active ingredient: lysophospholipids; LPL) levels on growth performance, nutrient ...digestibility, body composition, and serum profile in broilers. A total of 864 one-day-old male Ross 308 broilers (45.3 ± 0.6 g) was used in a 28-day experiment. Broilers were allotted to a 2 × 3 factorial arrangement design with 2 levels of energy (starter: ME = 2,950 kcal/kg for energy reduced diet and 3,050 kcal/kg for basal diet; finisher: ME = 3,100 kcal/kg for energy reduced diet and 3,200 kcal/kg for basal diet) and 3 levels of emulsifier supplementation (zero, 0.05, and 0.10%) according to their initial BW. There were 8 replicate cages per treatment with 18 broilers per cage. Broilers fed basal diets had higher (P < 0.05) body weight gain (BWG, d zero to 14) and lower (P < 0.05) feed conversion ratio (FCR, d zero to 14 and d zero to 28) than those fed reduced energy diets. Broilers fed LPL supplementation diets also had higher (P < 0.05) BWG (d zero to 14) and lower (P < 0.05) FCR (d zero to 14, d 15 to 28, and d zero to 28) than those fed without LPL supplementation diets. On d 14, the apparent total tract digestibility (ATTD) of DM, nitrogen (N), and gross energy (GE) was increased (P < 0.05) by LPL supplementation. The low density lipoprotein cholesterol, total cholesterol, and triglycerides concentrations also were decreased (P < 0.05) by LPL supplementation on d 14. The relative weight of abdominal fat was higher (P < 0.05) in basal diet treatments, but lower (P < 0.05) in LPL supplementation treatments. In conclusion, LPL supplementation can increase growth performance and nutrient digestibility, decrease cholesterol and triglycerides concentration in the starter period, and decrease the abdominal fat percentage in broilers.
Liquid-phase transmission electron microscopy (LPTEM) offers label-free imaging of nanoparticle (NP) processes in liquid with sub-nanometer spatial and millisecond temporal resolution. However, LPTEM ...studies have reported only on NPs moving orders of magnitude slower than expected from bulk aqueous liquid conditions, likely due to strong interactions with the LPTEM liquid-enclosing membranes. We demonstrate how scanning transmission electron microscope (STEM) imaging can be used to measure the motion of individual NPs and agglomerates, which are not hindered by such interactions. Only at low electron flux do we find that individual NPs exhibit Brownian motion consistent with optical control experiments and theoretical predictions for unhindered passive diffusive motion in bulk liquids. For increasing electron flux, we find increasingly faster than passive motion that still appears effectively Brownian. We discuss the possible origins of this beam–sample interaction. This establishes conditions for the use of STEM as a reliable tool for imaging nanoscale hydrodynamics in situ TEM.
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