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Parasitic nematodes devastate human and animal health. The limited number of anthelmintics available is concerning, especially because of increasing drug resistance. Anthelmintics are commonly derived from natural products, e.g. fungi and plants. This investigation aimed to develop a high-throughput whole organism screening method based on a motility assay using the wMicroTracker system. Anthelmintic activity of extracts from Hawaiian fungi was screened against third-stage larvae of the parasitic nematode Angiostrongylus cantonensis, categorized according to the degree of motility reduction. Of the 108 crude samples and fractionated products, 48 showed some level of activity, with 13 reducing motility to 0–25% of the maximum exhibited, including two pure compounds, emethacin B and epicoccin E, neither previously known to exhibit anthelmintic properties. The process of bioassay-guided fractionation is illustrated in detail based on analysis of one of the crude extracts, which led to isolation of lamellicolic anhydride, a compound with moderate activity. This study validates the wMicroTracker system as an economical and high-throughput option for testing large suites of natural products against A. cantonensis, adds to the short list of diverse parasites for which it has been validated and highlights the value of A. cantonensis and Hawaiian fungi for discovery of new anthelmintics.
To reduce fan noise and weight, according to the structural characteristics of a turbofan engine, a fan rotor with an ultra-low rotating speed is designed in this study by using a new concept of diffusion blade profiles in which the rotating speed of an ultra-highly loaded rotor is only 0.58 times that of a normally loaded rotor. To further examine the applicability of this rotor, its matching stator is also designed. The flow fields in the ultra-highly and normally loaded fan stages are simulated using the same numerical method to conduct an aerodynamic characteristic comparison. Compared with the normally loaded rotor, the sizes of the boundary layers on the blade surfaces, the wakes behind the blades and the flow losses of the ultra-highly loaded rotor are smaller. At the design point, the efficiency of the ultra-highly loaded fan stages is higher than that of the normally loaded stage; moreover, the surge margin of the former is evidently larger than that of the latter. The ultra-highly loaded fan could be a good candidate for use in Ultra-High Bypass Ratio Geared Turbofan (UHBRGT) technology.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
Background: Pertussis continues to be an important health issue in Vietnam despite infant vaccination programs. In Vietnam, the incidence rates of pertussis per 100,000 population rose from 0.09 in 2014 to 0.33 in 2015 and to 0.58 in 2017. Macrolides, especially erythromycin, are the treatment of choice. However, erythromycin-resistant cases, caused by transition at A2047G position in 23S rRNA, have been reported in the region. Few data are available on antimicrobial resistance in Bordetella pertussis to guide treatment in Vietnam. We report antimicrobial susceptibility of the circulating strains in southern Vietnam during 2015–2017. Methods: Tracheal aspirates from 263 suspected pertussis cases were subject to multiplex real-time PCR to identify B. pertussis and Bordetella spp. Samples were cultured on Regan Lowe agar with 10% sheep blood containing cephalexin (40 µg/mL) and incubated at 37°C for 10 days. The antimicrobial susceptibilities to erythromycin, azithromycin, clarithromycin, and trimethoprim/sulfamethoxazole were determined using the disc diffusion method (CLSI-2017) on Regan Lowe and Mueller Hinton agar. Erythromycin minimum inhibitory concentrations (MICs) were determined using an E-test. The results were recorded after days 3 and 7 of incubation. Sequencing of the 23S rRNA gene was performed to detect mutations conferring macrolide resistance. Results: Of 263 cases, 119 were positive for B. pertussis (45.2%) by real-time PCR, and 15 of 263 strains (5.7%) were successfully cultured. All 15 isolates were susceptible to macrolides and no heterogeneous phenotype was recorded after 7 days; erythromycin MICs were ≤0.094 µg/mL (Fig. 1). We observed no difference in results generated on Regan Lowe and Mueller Hinton media. However, for testing trimethoprim/sulfamethoxazole, results on were superior, as those on Regan Lowe media were unclear. Sequencing of 23S rRNA identified no mutations known to confer macrolide resistance. Conclusions: None of 15 B. pertussis isolates tested were nonsusceptible to erythromycin and macrolides. Similarly, no mutation at the erythromycin-binding site in the 23S rRNA gene was identified. The low isolation rate of B. pertussis by culture means that few positive specimens were tested for antimicrobial susceptibility. To overcome this limitation, detection of resistance directly from clinical specimens needs to be investigated. Ongoing screening for B. pertussis and antimicrobial susceptibility is recommended to support efforts to control the spread of this respiratory tract infection agent.
Background: Whooping cough is a serious respiratory illness in infants caused by Bordetella pertussis. In spite of the vaccination program, the incidence rates of whooping cough per 100,000 population in Vietnam increased from 0.33 in 2015 to 0.58 in 2017. If this represents a pertussis resurgence, contributors may include pathogen adaptation, the spread of specific variants, vaccine failure, and failure to effectively treat cases and contacts. There has been little research in Vietnam on B. pertussis strains. Therefore, we investigated the molecular epidemiology of circulating B. pertussis strains in Southern Vietnam by applying multilocus sequence typing (MLST) for 7 housekeeping genes and 4 antigenic determinant genes as components in the acellular vaccine including prn, ptxP, ptxS1, and fim3. Methods: DNA was extracted from 15 isolates collected from 263 case patients during 2015–2017 and was subject to MLST using primers and cycling conditions from the Bordetella pubMLST website (www.Pubmlst.org/Bordetella/). The products were analyzed using BioEdit version 7.2.5 software and then were aligned and compared to reference sequences of each genotype in the database. The evolutionary relationship among sequence types (STs) from housekeeping genes was performed as a minimum spanning tree via the goeBURST algorithm, whereas the correlation of different variants from 4 antigenic determinant genes was built up and clarified with phylogenetic trees based on the UPGMA method by MEGA 7 program. Results: The 15 isolates were all classified as ST2 (100%) by MLST of housekeeping genes, and they belonged to a common global clonal group (Fig. 1). Sequencing of antigenic determinant genes prn2 – ptxP3 – ptxS1-1 – fim3-1 determined that all were identical to each another and the reference sequences (Fig. 2). Conclusions:B. pertussis isolates circulating in Southern Vietnam appeared to be the same as the common global strain. Few isolates were available for testing; therefore, continued surveillance is important to confirm these findings and to monitor population changes over time.
Previous work led to the proposal that the precision feeding of a high-concentrate diet may represent a potential method with which to enhance feed efficiency (FE) when rearing dairy heifers. However, the physiological and metabolic mechanisms underlying this approach remain unclear. This study used metabolomics analysis to investigate the changes in plasma metabolites of heifers precision-fed diets containing a wide range of forage to concentrate ratios. Twenty-four half-sib Holstein heifers, with a similar body condition, were randomly assigned into four groups and precision fed with diets containing different proportions of concentrate (20%, 40%, 60% and 80% based on DM). After 28 days of feeding, blood samples were collected 6 h after morning feeding and gas chromatography time-of-ﬂight/MS was used to analyze the plasma samples. Parameters of oxidative status were also determined in the plasma. The FE (after being corrected for gut fill) increased linearly (P < 0.01) with increasing level of dietary concentrate. Significant changes were identified for 38 different metabolites in the plasma of heifers fed different dietary forage to concentrate ratios. The main pathways showing alterations were clustered into those relating to carbohydrate and amino acid metabolism; all of which have been previously associated with FE changes in ruminants. Heifers fed with a high-concentrate diet had higher (P < 0.01) plasma total antioxidant capacity and superoxide dismutase but lower (P ≤ 0.02) hydroxyl radical and hydrogen peroxide than heifers fed with a low-concentrate diet, which might indicate a lower plasma oxidative status in the heifers fed a high-concentrate diet. Thus, heifers fed with a high-concentrate diet had higher FE and antioxidant capacity but a lower plasma oxidative status as well as changed carbohydrate and amino acid metabolism. Our findings provide a better understanding of how forage to concentrate ratios affect FE and metabolism in the precision-fed growing heifers.
Post-stroke depression (PSD) is the most common psychiatric complication facing stroke survivors and has been associated with increased distress, physical disability, poor rehabilitation, and suicidal ideation. However, the pathophysiological mechanisms underlying PSD remain unknown, and no objective laboratory-based test is available to aid PSD diagnosis or monitor progression.
Here, an isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic approach was performed to identify differentially expressed proteins in plasma samples obtained from PSD, stroke, and healthy control subjects.
The significantly differentiated proteins were primarily involved in lipid metabolism and immunoregulation. Six proteins associated with these processes – apolipoprotein A-IV (ApoA-IV), apolipoprotein C-II (ApoC-II), C-reactive protein (CRP), gelsolin, haptoglobin, and leucine-rich alpha-2-glycoprotein (LRG) – were selected for Western blotting validation. ApoA-IV expression was significantly upregulated in PSD as compared to stroke subjects. ApoC-II, LRG, and CRP expression were significantly downregulated in both PSD and HC subjects relative to stroke subjects. Gelsolin and haptoglobin expression were significantly dysregulated across all three groups with the following expression profiles: gelsolin, healthy control > PSD > stroke subjects; haptoglobin, stroke > PSD > healthy control.
Early perturbation of lipid metabolism and immunoregulation may be involved in the pathophysiology of PSD. The combination of increased gelsolin levels accompanied by decreased haptoglobin levels shows promise as a plasma-based diagnostic biomarker panel for detecting increased PSD risk in post-stroke patients.
Acupuncture, as complementary medicine, has been used since many years ago in china and many researches have proved its effect separately or combined with other treatment methods.
To compare therapeutic effects of Acupuncture plus estazolam and Cognitive - Behavioral Therapies plus estazolam on insomnia.
To determine the efficacy of acupuncture as complementary medicine in treating insomnia.
64 insomnia patients were randomly divided into an acupuncture group and a behavioral group, 30 cases in acupuncture group and 18 cases in behavioral group completed research. The acupuncture group was treated by administration oral estazolam before sleeping each day and needling, three times a week, the behavioral group received Stimulus control as Cognitive - Behavioral Therapy plus oral estazolam before sleeping each day. Treatment course was 3 weeks. The insomnia severity index (ISI) scores before and after treatment were observed in the both groups.
The total effective rate was 86.7% in the acupuncture group and 50% in the behavioral group with statistically significant difference (P < 0.05). The cured rate of 30% in the acupuncture group was significantly higher than 16.7% in the behavioral group (both P < 0.05).
The therapeutic effect of Acupuncture as a complementary medicine on insomnia is better than stimulus therapy as a Cognitive - Behavioral Therapy.
Some studies have shown that the excessive metabolic heat production is the primary cause for dead chicken embryos during late embryonic development. Increasing heat shock protein (HSP) expression and adjusting metabolism are important ways to maintain body homeostasis under heat stress. This study was conducted to investigate the effects of in ovo injection (IOI) of vitamin C (VC) at embryonic age 11th day (E11) on HSP and metabolic genes expression. A total of 320 breeder eggs were randomly divided into normal saline and VC injection groups. We detected plasma VC content and rectal temperature at chick’s age 1st day, and the mRNA levels of HSP and metabolic genes in embryonic livers at E14, 16 and 18, analysed the promoter methylation levels of differentially expressed genes and predicted transcription factors at the promoter regions. The results showed that IOI of VC significantly increased plasma VC content and decreased rectal temperature (P < 0.05). In ovo injection of VC significantly increased heat shock protein 60 (HSP60) and pyruvate dehydrogenase kinase 4 (PDK4) genes expression at E16 and PDK4 and secreted frizzled related protein 1 (SFRP1) at E18 (P < 0.05). At E16, IOI of VC significantly decreased the methylation levels of total CpG sites and −336 CpG site in HSP60 promoter and −1137 CpG site in PDK4 promoter (P < 0.05). Potential binding sites for nuclear factor-1 were found around −389 and −336 CpG sites in HSP60 promoter and potential binding site for specificity protein 1 was found around −1137 CpG site in PDK4 promoter. Our results suggested that IOI of VC increased HSP60, PDK4 and SFRP1 genes expression at E16 and 18, which may be associated with the demethylation in gene promoters. Whether IOI of VC could improve hatchability needs to be further verified by setting uninjection group.
Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
Nitroethane (NE), 2-nitroethanol (NEOH) and 2-nitro-1-propanol (NPOH) were investigated in order to determine their inhibitory effects on in vitro ruminal fermentation and methane (CH4) production of a hay-rich substrate (alfalfa hay: maize meal = 4:1, w/w). The rumen liquor collected from cannulated Holstein dairy cows was incubated at 39 °C for 72 h. The addition of NE, NEOH and NPOH slowed down the fermentation process and notably decreased molar CH4 proportion by 96.8, 96.4 and 35.0%, respectively. The abundance of total methanogen and methanogens from the order Methanobacteriales were all decreased with NE, NEOH and NPOH supplementation. Meanwhile, the nitrocompound addition reduced mcrA gene expression, coenzyme F420 and F430 contents. The correlation analysis showed that CH4 production was correlated positively with the population abundance of total methanogens, Methanobacteriales, mcrA gene expression, coenzyme contents of F420 and F430. The nitrocompound addition decreased acetate concentration and increased propionate and butyrate concentrations in the culture fluid. In summary, both NE and NEOH addition presented nearly the same inhibitory effectiveness on in vitro CH4 production; they were more effective than NPOH. The results of the current study provide evidence that NE, NEOH and NPOH can dramatically decrease methanogen population, mcrA gene expression and the coenzyme content of F420 and F430 in ruminal methanogenesis.
Two-dimensional particle-in-cell (PIC) simulations have been used to investigate the interaction between a laser pulse and a foil exposed to an external strong longitudinal magnetic field. Compared with that in the absence of the external magnetic field, the divergence of proton with the magnetic field in radiation pressure acceleration (RPA) regimes has improved remarkably due to the restriction of the electron transverse expansion. During the RPA process, the foil develops into a typical bubble-like shape resulting from the combined action of transversal ponderomotive force and instabilities. However, the foil prefers to be in a cone-like shape by using the magnetic field. The dependence of proton divergence on the strength of magnetic field has been studied, and an optimal magnetic field of nearly 60 kT is achieved in these simulations.
Copy number variations (CNVs), as an important source of genetic variation, can affect a wide range of phenotypes by diverse mechanisms. The somatostatin receptor 2 (SSTR2) gene plays important roles in cell proliferation and apoptosis. Recently, this gene was mapped to a CNV region, which encompasses quantitative trait loci of cattle economic traits including body weight, marbling score, etc. Therefore, SSTR2 CNV may exhibit phenotypic effects on cattle growth traits. In the current study, distribution of SSTR2 gene CNVs was investigated in six Chinese cattle breeds (XN, QC, NY, JA, LX and PN), and the results showed higher CNV polymorphisms in XN, QC and NY cattle. Next, association analysis between growth traits and SSTR2 CNV was performed for XN, QC and NY cattle. In NY, individuals with fewer copies showed better performance than those with more copies. Further, the effects of SSTR2 CNV on the SSTR2 mRNA level were also investigated, but revealed no significant correlation in either muscle or adipose tissue of adult NY cattle. The results suggested the potential for use of SSTR2 CNV as a marker for the molecular breeding of NY cattle.
Beijing–Tianjin–Hebei is the largest urban agglomeration in northern China, but the spatiotemporal patterns and risk factors concerning hepatitis B virus (HBV) incidence in this area have been unclear. The present study aimed to reveal the spatiotemporal epidemiological features of HBV infection and quantify the association between HBV infection and socio-economic risk factors. The data on HBV cases in Beijing–Tianjin–Hebei from 2007 to 2012 was collected for each county. The Bayesian space–time hierarchy model and the GeoDetector method were used to reveal spatiotemporal patterns and detect risk factors. High-risk regions were mainly distributed in the underdeveloped rural areas in the north and mid-south of the study region, while low-risk regions were mainly distributed in the urban and western areas. The HBV annual incidence rate decreased substantially over the 6-year period, dropping from 7.34/105 to 5.51/105. Compared with this overall trend, 38.5% of high-risk counties showed a faster decrease, and 35.9% of high-risk counties exhibited a slower decrease. Meanwhile, 29.7% of low-risk counties had a faster decrease, and 44.6% of low-risk counties exhibited a slower decrease. Socio-economic factors were strongly associated with the spatiotemporal patterns and variation. The population density and gross domestic product per capita were negatively associated with HBV transmission, with determinant powers of 0.17 and 0.12, respectively. The proportion of primary industry and the number of healthcare workers were positively associated with the disease incidence, with determinant powers of 0.11 and 0.8, respectively. The interactive effect between population density and the other factors exerted a greater influence on HBV transmission than that of these factors measured independently.
Soybean [Glycine max (L.) Merr.] is one of the most important legume crops in the world. However, soybean grain yield is extensively affected by environmental stresses such as soil salinity. In this study, we evaluated the germplasm of 51 Indonesian soybean accessions for salt tolerance to identify salt-tolerant germplasms for possible use in breeding for soybean salt tolerance. Based on experiments under hydroponic conditions, adding 100 mM of NaCl to a 1/2 concentration of Hoagland and Arnon solution, several Indonesian soybean germplasms, such as Java 7, Seputih Raman, Tambora, Ringgit (JP 30217), Sinyonya (early) and Sinyonya (late) were identified as salt-tolerant in terms of salt tolerance rate (STR) and leaf chlorophyll content (SPAD value) taken with the Konica Minolta SPAD-502 chlorophyll meter. The selected salt-tolerant germplasms were further evaluated under soil medium cultivation in pots irrigated with 100 mM NaCl for around 5 weeks. The six selected soybean germplasms again showed higher salt tolerance in terms of SPAD, STR and shoot dry weight. Expression analysis of the salt tolerance gene Ncl revealed a significant positive correlation between Ncl expression and salt tolerance, suggesting that Ncl is essential for salt tolerance in the Indonesian soybean germplasms we tested. The salt-tolerant Indonesian soybean germplasms identified in this study could be used in local soybean breeding practices for the improvement of salt tolerance.
Starch digestion in the small intestines of the dairy cow is low, to a large extent, due to a shortage of syntheses of α-amylase. One strategy to improve the situation is to enhance the synthesis of α-amylase. The mammalian target of rapamycin (mTOR) signalling pathway, which acts as a central regulator of protein synthesis, can be activated by leucine. Our objectives were to investigate the effects of leucine on the mTOR signalling pathway and to define the associations between these signalling activities and the synthesis of pancreatic enzymes using an in vitro model of cultured Holstein dairy calf pancreatic tissue. The pancreatic tissue was incubated in culture medium containing l-leucine for 3 h, and samples were collected hourly, with the control being included but not containing l-leucine. The leucine supplementation increased α-amylase and trypsin activities and the messenger RNA expression of their coding genes (P <0.05), and it enhanced the mTOR synthesis and the phosphorylation of mTOR, ribosomal protein S6 kinase 1 and eukaryotic initiation factor 4E-binding protein 1 (P <0.05). In addition, rapamycin inhibited the mTOR signal pathway factors during leucine treatment. In sum, the leucine regulates α-amylase and trypsin synthesis in dairy calves through the regulation of the mTOR signal pathways.
The strong-coupling mode, called the “quasimode”, is excited by stimulated Brillouin scattering (SBS) in high-intensity laser–plasma interactions. Also SBS of the quasimode competes with SBS of the fast mode (or slow mode) in multi-ion species plasmas, thus leading to a low-frequency burst behavior of SBS reflectivity. Competition between the quasimode and the ion-acoustic wave (IAW) is an important saturation mechanism of SBS in high-intensity laser–plasma interactions. These results give a clear explanation of the low-frequency periodic burst behavior of SBS and should be considered as a saturation mechanism of SBS in high-intensity laser–plasma interactions.
This study investigated Echinococcus genotypes in patients with hydatidosis that reside in Inner Mongolia, Tibet or Qinghai Province by partially sequencing the cytochrome c oxidase subunit 1 (cox1) and NADH dehydrogenase 1 (nad1) genes. Cyst fluids were collected from 23 patients with hydatidosis and DNA was extracted. Portions of the cox1 and nad1 genes were amplified and subsequently sequenced. Sequencing analysis determined that one of the isolates contained Echinococcus multilocularis, and the other 22 isolates contained E. granulosus sensu lato. The isolates were then further classified based on genotype, and E. granulosus sensu stricto (s.s.) G1 (n = 20), E. granulosus s.s. G3 (n = 1) and E. canadensis G6/7 (n = 1) were identified. Additionally, the sequences were concatenated (pcox1 + pnad1) and 11 haplotypes were identified among the E. granulosus s.s. isolates (G1 and G3), with a shared common haplotype (H1) identified. Overall, these findings provide further understanding of the genetic patterns of Echinococcus in western and northern China.
Previous studies showed that spermine could protect the organism from oxidative damage in vivo. However, in vivo information on the antioxidant-related underlying molecular mechanism of spermine is limited. In this experiment, we further evaluated the effects of spermine supplementation and extended spermine administration on the antioxidant status and antioxidant-related signaling molecules gene expression in the liver and longissimus dorsi of piglets. A total of 80 piglets were randomly distributed to two groups, that is, those with adequate nutrient intake administrated with spermine (0.4 mmol/kg BW) or those with restricted nutrient intake supplemented by saline. The piglets were fed in pairs for 7 h or 3, 6, or 9 days. The results are as follows: (1) spermine can promote the antioxidant capacity by increasing enzymatic antioxidant capacity, glutathione content and clearance of oxygen radicals; (2) spermine significantly increased the mRNA levels of enzymatic antioxidant substances, NF-E2-related nuclear factor 2, Kelch-like ECH-associated protein 1, and the mammalian target of rapamycin but decreased the mRNA levels of ribosomal p70 S6 kinase in the liver and longissimus dorsi of the piglets.