Pigeons, as the only altricial birds in poultry, are the primary Trichomonas gallinae (T. gallinae) host. To study the effects of T. gallinae infection on gut microbiota, we compared the microbiota diversity and composition in gastrointestinal (GI) tracts of pigeons at the age of 14 and 21 day with different degrees of T. gallinae infection. Thirty-six nestling pigeons were divided into three groups: the healthy group, low-grade and high-grade trichomonosis group. Then, the crop, small intestine and rectum contents were obtained for sequencing of the 16S rRNA gene V3-V4 hypervariable region. The results showed that the microbiota diversity was higher in crop than in small intestine and rectum, and the abundance of Lactobacillus genus was dominant in small intestine and rectum of healthy pigeons at 21 days. T. gallinae infection decreased the microbiota richness in crop at 14 days. The abundance of the Firmicutes phylum and Lactobacillus genus in small intestine of birds at 21 days were decreased by infection, however the abundances of Proteobacteria phylum and Enterococcus, Atopobium, Roseburia, Aeriscardovia and Peptostreptococcus genus increased. The above results indicated that crop had the highest microbiota diversity among GI tract of pigeons, and the gut microbiota diversity and composition of pigeon squabs were altered by T. gallinae infection.
Maize (Zea mays L.)/pea (Pisum sativum L.) strip intercropping is considered a promising cropping system to boost crop productivity. The 3-year (2009-2011) field experiment was conducted at Wuwei, northwest China, with two maize to pea strip width ratios (80:80 cm and 120:80 cm), each under three N fertilizer rates (0, 90 and 135 kg N ha(-1) for pea, and 0, 300, and 450 kg N ha(-1) for maize). The results showed that expanding maize to pea strip width ratio from 80:80 cm to 120:80 cm coupled with a reduction of N fertilizer rate intensified N competition and improved N compensation. The apparent N recovery and N utilization efficiency of intercropped pea with strip width ratio of 120:80 cm were increased by 8.0% and 8.9% compared to strip width ratio of 80:80 cm. Compared to high N rate, the two indicators of intercropped pea with lowered N rate were increased by 10.0% and 6.0%. For intercropped maize, the two indicators were increased by 6.8% and 5.1%, with strip width ratio of 120:80 cm compared to 80:80 cm. Also, they were improved by 9.7% and 11.5%, with lowered N rate compared to high N rate. Consequently, the grain yield of pea and maize in the 120:80 cm pattern was improved by 11.9% and 7.7% compared to 80:80 cm. We concluded that expanding maize to pea strip ratio coupled with N fertilizer reduction can optimize N complementary use.
Stress-related neuropsychiatric disorders are widespread, debilitating and often treatment-resistant illnesses that represent an urgent unmet biomedical problem. Animal models of these disorders are widely used to study stress pathogenesis. A more recent and historically less utilized model organism, the zebrafish (Danio rerio), is a valuable tool in stress neuroscience research. Utilizing the 5-week chronic unpredictable stress (CUS) model, here we examined brain transcriptomic profiles and complex dynamic behavioral stress responses, as well as neurochemical alterations in adult zebrafish and their correction by chronic antidepressant, fluoxetine, treatment. Overall, CUS induced complex neurochemical and behavioral alterations in zebrafish, including stable anxiety-like behaviors and serotonin metabolism deficits. Chronic fluoxetine (0.1 mg/L for 11 days) rescued most of the observed behavioral and neurochemical responses. Finally, whole-genome brain transcriptomic analyses revealed altered expression of various CNS genes (partially rescued by chronic fluoxetine), including inflammation-, ubiquitin- and arrestin-related genes. Collectively, this supports zebrafish as a valuable translational tool to study stress-related pathogenesis, whose anxiety and serotonergic deficits parallel rodent and clinical studies, and genomic analyses implicate neuroinflammation, structural neuronal remodeling and arrestin/ubiquitin pathways in both stress pathogenesis and its potential therapy.
The objectives of this study were to examine the intra and inter-operator reliability of shear wave elastography (SWE) device in quantifying the shear modulus of thoracolumbar fascia (TLF) and the device's abilities to examine the shear modulus of the TLF during upper body forward. Twenty healthy male subjects participated in this study (mean age: 18.4 +/- 0.7 years). Two independent operators performed the shear modulus of TLF during upper body forward using SWE, and interclass correlation coefficient (ICC) and minimum detectable change (MDC) were calculated. The shear modulus of the TLF was quantified by operator A using SWE at upper body forward 60 degrees. The intra-operator (ICC=0.860-0.938) and inter-operator (ICC=0.904-0.944) reliabilities for measuring the shear modulus of the TLF with the upper body forward 0 degrees were rated as both excellent, and the MDC was 4.71 kPa. The TLF shear modulus of upper body forward 60 degrees was increased 45.5% (L3) and 55.0% (L4) than that of upper body forward 0 degrees. The results indicate that the SWE is a dependable tool to quantify the shear modulus of TLF and monitor its dynamic changes. Therefore, this device can be used for biomechanical study and intervention experiments of TLF.
Consistent use of large amounts of fertilizers, pesticides, and mulch can cause the accumulation of harmful substances in cotton plants. Among these harmful substances, cadmium (Cd), an undegradable element, stands out as being particularly highly toxic to plants. The objective of this study was to evaluate the ability of biochar (3%) and biofertilizer (1.5%) to decrease Cd uptake, increase cotton dry weight, and modulate the activities of photosynthetic and peroxidase (POD), superoxide dismutase (SOD), catalase enzyme (CAT) in cotton (Gossypium hirsutum L.) grown in Cd-contaminated soil (0, 1, 2, or 4 mg Cd kg(-1) soil) in pots. These studies showed that, as expected, exogenous Cd adversely affects cotton chlorophyll and photosynthesis. However, biochar and biofertilizer increased cotton dry weight by an average of 16.82% and 32.62%, respectively. Meanwhile, biochar and biofertilizer decreased the accumulation of Cd in cotton organs, and there was a significant reduction in the amount of Cd in bolls (P<0.05). Biochar and biofertilizer have a positive impact on cotton chlorophyll content, net photosynthesis, stomatal conductance, transpiration rate, and intercellular CO2 concentration. Thus, the addition of biochar and biofertilizer promote cotton growth. However, biochar and biofertilizer increased the SOD activity of leaves (47.70% and 77.21%), CAT activity of leaves (35.40% and 72.82%), SOD activity of roots (33.62% and 39.37%), and CAT activity of roots (36.91% and 60.29%), respectively, and the addition of biochar and biofertilizer decreased the content of MDA and electrolyte leakage rate. Redundancy analyses showed that biochar and biofertilizer also improved SOD and POD activities by reducing the heavy metal-induced oxidative stress in cotton and reducing Cd uptake in cotton organs. Therefore, biochar and biofertilizer have a positive effect on the growth of cotton.
Galfenol (Iron-gallium) alloys have attracted significant attention as the promising magnetostrictive materials. However, the as-cast Galfenols exhibit the magnetostriction within the range of 20-60 ppm, far below the requirements of high-resolution functional devices. Here, based on the geometric crystallographic relationship, we propose to utilize the 90 degrees -domain switching to improve the magnetostriction of Galfenols by tuning the crystal growth direction (CGD) along the easy magnetization axis (EMA). Our first-principles calculations demonstrate that Pt doping can tune the CGD of Galfenol from  to , conforming to the EMA. Then, it is experimentally verified in the (Fe0.83Ga0.17)(100-x)Pt-x (x=0, 0.2, 0.4, 0.6, 0.8 and 1.0) alloys and the magnetostriction is greatly improved from 39 ppm (x=0, as-cast) to 103 ppm (x=0.8, as-cast) and 188 ppm (x=0.8, directionally solidified), accompanying with the increasing CGD alignment along . The present study provides a novel approach to design and develop high-performance magnetostrictive materials.
Liver metastasis is a recalcitrant disease that usually leads to death of the patient. The present study established a unique patient-derived orthotopic xenograft (PDOX) nude mouse model of a highly aggressive liver metastasis of colon cancer. The aim of the present study was to demonstrate proof-of-concept that candidate drug combinations could significantly inhibit growth and re-metastasis of this recalcitrant tumor. The patient's liver metastasis was initially established subcutaneously in nude mice and the subcutaneous tumor tissue was then orthotopically implanted in the liver of nude mice to establish a PDOX model. Two studies were performed to test different drugs or drug combination, indicating that 5-fluorouracil (5-FU)+irinotecan (IRI)+bevacizumab (BEV) and regorafenib (REG)+selumetinib (SEL) had significantly inhibited liver metastasis growth (p=0.013 and p=0.035, respectively), and prevented liver satellite metastasis. This study is proof of concept that a PDOX model of highly aggressive colon-cancer metastasis can identify effective drug combinations and that the model has future clinical potential.
In neuroscience, computational modeling is an effective way to gain insight into cortical mechanisms, yet the construction and analysis of large-scale network models-not to mention the extraction of underlying principles-are themselves challenging tasks, due to the absence of suitable analytical tools and the prohibitive costs of systematic numerical exploration of high-dimensional parameter spaces. In this paper, we propose a data-driven approach assisted by deep neural networks (DNN). The idea is to first discover certain input-output relations, and then to leverage this information and the superior computation speeds of the well-trained DNN to guide parameter searches and to deduce theoretical understanding. To illustrate this novel approach, we used as a test case a medium-size network of integrate-and-fire neurons intended to model local cortical circuits. With the help of an accurate yet extremely efficient DNN surrogate, we revealed the statistics of model responses, providing a detailed picture of model behavior. The information obtained is both general and of a fundamental nature, with direct application to neuroscience. Our results suggest that the methodology proposed can be scaled up to larger and more complex biological networks when used in conjunction with other techniques of biological modeling.
The purpose of the present study was to evaluate the diagnostic role of CRP in ovarian cancer and to assess whether CRP can be combined with tumor markers to enhance the diagnostic efficacy toward ovarian cancer. Area under the curve, sensitivity, and specificity were calculated to access the diagnostic ability of each singly and combined as markers for ovarian cancer. The CRP cut-off value was then calculated to evaluate the diagnostic efficacy of CRP for ovarian cancer. Our results showed that values for all markers were significantly higher in the cancer group than in the control group. Receiver operating characteristic curve results showed that CA125 had the highest diagnostic efficacy for ovarian cancer, while the sensitivity for CRP was higher than for CA125, and the specificity for CRP was equal to that of CA125. The combination of CRP, CA125, and HE4, however, provided the strongest diagnostic capability. Furthermore, the diagnostic cut-off value for CRP with regard to ovarian cancer was 9.8 mg/L, and high levels of CRP were correlated with stage and tumor size of ovarian cancer. Our study indicated that CRP is valuable in the diagnosis of ovarian cancer, and that combining CRP with CA125 and HE4 improved the diagnostic efficacy with respect to ovarian cancer.
Obesity and its associated metabolic disorders are increasingly impacting public health worldwide. Sphingosine kinase 1 (Sphk1) is a critical enzyme in sphingolipid metabolism that has been implicated in various metabolic syndromes. In this study, we developed a mouse model constitutively expressing pseudoacetylated mouse Sphk1 (QSPHK1) to study its role in regulating glucose and lipid metabolism. The results showed that QSPHK1 mice gained less body weight than wide type (WT) mice on a high-fat diet, and QSPHK1 mice had improved glucolipid metabolism and insulin. Moreover, QSPHK1 mice had alleviated hepatic triglyceride accumulation and had high-fat-diet-induced hepatic steatosis that occurred as a result of reduced lipogenesis and enhanced fatty acid oxidation, which were mediated by the AMPK/ACC axis and the FGF21/adiponectin axis. Collectively, this study provided evidence that the K27Q/K29Q mutations of Sphk1 could have a protective role in preventing obesity and the related metabolic diseases. Hence, our results contribute to further understanding of the biological functions of Sphk1, which has great pharmaceutical implications.
Gaussia luciferase (GLuc) is a small luciferase (18.2 kDa; 168 residues) and is thus attracting much attention as a reporter protein, but the lack of structural information is hampering further application. Here, we report the first solution structure of a fully active, recombinant GLuc determined by heteronuclear multidimensional NMR. We obtained a natively folded GLuc by bacterial expression and efficient refolding using a Solubility Enhancement Petide (SEP) tag. Almost perfect assignments of GLuc's H-1, C-13 and N-15 backbone signals were obtained. GLuc structure was determined using CYANA, which automatically identified over 2500 NOEs of which>570 were long-range. GLuc is an all-alpha-helix protein made of nine helices. The region spanning residues 10-18, 36-81, 96-145 and containing eight out of the nine helices was determined with a C-alpha-atom RMSD of 1.39 angstrom +/- 0.39 angstrom. The structure of GLuc is novel and unique. Two homologous sequential repeats form two anti-parallel bundles made by 4 helices and tied together by three disulfide bonds. The N-terminal helix 1 is grabbed by these 4 helices. Further, we found a hydrophobic cavity where several residues responsible for bioluminescence were identified in previous mutational studies, and we thus hypothesize that this is a catalytic cavity, where the hydrophobic coelenterazine binds and the bioluminescence reaction takes place.
Miniaturization and integration of optical tweezers are attractive. Optical fiber-based trapping systems allow optical traps to be realized in miniature systems, but the optical traps in these systems lack reliability or mobility. Here, we present the all-fiber modular optical tweezers (AFMOTs), in which an optical trap can be reliably created and freely moved on a sample substrate. Two inclined optical fibers are permanently fixed to a common board, rendering a modular system where fiber alignments are maintained over months. The freely movable optical trap allows particles to be trapped in their native locations. As a demonstration, we applied AFMOTs to trap and deform freely floating individual cells. By the cell mechanical responses, we differentiated the nontumorigenic breast epithelial cell line (MCF10A) from its cancerous PTEN mutants (MCF10 PTEN-/-). To further expand the functionalities, three modalities of AFMOTs are demonstrated by changing the types of fibers for both the optical trap creation and particle position detection. As a miniature and modular system that creates a reliable and mobile optical trap, AFMOTs can find potential applications ranging from point-of-care diagnostics to education, as well as helping transition the optical trapping technology from the research lab to the field.
Polyphenols based bioactive compounds from vegetables and fruits are known for impressive antioxidant activity. Ingestion of these antioxidants may promote human health against cardiovascular diseases and cancer. Mango is a popular tropical fruit with special taste, high nutritional value and health-enhancing metabolites. The aim was to investigate the diversity of phytochemicals between two mango cultivars of china at three stages of fruit maturity. We used ESI-QTRAP-MS/MS approach to characterize comprehensively the metabolome of two mango cultivars named Hongguifei (HGF) and Tainong (TN). HPLC was used to quantify selected catechin based phenolic compounds. Moreover, real-time qPCR was used to study the expression profiles of two key genes (ANR and LAR) involved in proanthocyanidin biosynthesis from catechins and derivatives. A total of 651 metabolites were identified, which include at least 257 phenolic compounds. Higher number of metabolites were differentially modulated in peel as compared to pulp. Overall, the relative quantities of amino acids, carbohydrates, organic acids, and other metabolites were increased in the pulp of TN cultivar. While the contents of phenolic compounds were relatively higher in HGF cultivar. Moreover, HPLC based quantification of catechin and derivatives exhibited cultivar specific variations. The ANR and LAR genes exhibited an opposite expression profile in both cultivars. Current study is the first report of numerous metabolites including catechin-based derivatives in mango fruit. These findings open novel possibilities for the use of mango as a source of bioactive compounds.
Diet is an important component in weight management strategies, but heterogeneous responses to the same diet make it difficult to foresee individual weight-loss outcomes. Omics-based technologies now allow for analysis of multiple factors for weight loss prediction at the individual level. Here, we classify weight loss responders (N=106) and non-responders (N=97) of overweight non-diabetic middle-aged Danes to two earlier reported dietary trials over 8 weeks. Random forest models integrated gut microbiome, host genetics, urine metabolome, measures of physiology and anthropometrics measured prior to any dietary intervention to identify individual predisposing features of weight loss in combination with diet. The most predictive models for weight loss included features of diet, gut bacterial species and urine metabolites (ROC-AUC: 0.84-0.88) compared to a diet-only model (ROC-AUC: 0.62). A model ensemble integrating multi-omics identified 64% of the non-responders with 80% confidence. Such models will be useful to assist in selecting appropriate weight management strategies, as individual predisposition to diet response varies.
Duodenal dysbiosis may be potential infection risks in patients with severe acute pancreatitis (SAP). Acid-suppression drugs (ACDs) are widely used in SAP patients in Asian countries. However, the impact of ACDs on duodenal microbiota during the early phase of SAP is still unknown. This randomized controlled clinical trial evaluated the impacts of esomeprazole (Eso), one of ACDs on duodenal microbiota during the first week of SAP with duodenal aspirates culture and 16sRNA Illumina sequencing analysis. 66 patients were randomized as 1:1 ratio into Eso group (Eso 40 mg/day) and Eso-N group (no Eso). The occurrence of duodenal bacterial overgrowth (DBO) was significantly higher in Eso group (about 85%) than that in Eso-N group (about 42%). The duodenal microbiota of the SAP patients shifted away from that of the normal control. There were differences between the Eso-N and Eso groups including enriched abundances of the class Negativicutes, order Selenomonadales and genus Veillonella. Acid suppression significantly increased incidence of Candida oesophagitis (CE) by 8-folds but did not increase other infectious events. In conclusion, acid suppression greatly increased the occurrence of DBO, duodenal dysbiosis and CE during the first week of SAP. Restrictive use of acid-suppressing medications might be helpful to reduce CE and potential risk of pancreatic infection in SAP patients.Trial registration: Chictr.org, ChiCTR-IPR-16008301, Registered April 18 2016, http://www.chictr.org.cn/showproj.aspx?proj=14089.