Clinical efficacy of 9-oxo-10, 11-dehydroageraphorone extracted from Eupatorium adenophorum against Psoroptes cuniculi in rabbits

BACKGROUND: Animal acariasis is one of the important veterinary skin diseases. Chemical drugs have been widely used to treat and control this kind of disease. But many chemicals control could increase resistance in target species, toxicity and environmental hazards. We found that the 9-oxo-10, 11-dehydroageraphorone (euptox A) extracted from E. adenophorum has strong toxicity against P. cuniculi in vitro, but the in vivo acaricidal actions of euptox A have yet to be investigated. RESULTS: A 14-day experiment was performed using rabbits that were naturally infested with P. cuniculi on a farm. Rabbits were randomly divided into five groups; animals in groups A, B and C were treated in each ear topically with 4.0 ml of 2.0 and 1.0 g/L (w/v) euptox A, respectively. Animals in groups D and E were treated with ivermectin (by injection; positive controls) and glycerol with water only (by embrocation; negative controls), respectively. Each rabbit was treated twice with separate treatments on days 0 and 7. Rabbits were observed daily and detailed examinations were performed on days 0, 7 and 14, to inspect the presence or absence of mites and scabs/crusts. Seven days after the initial treatment, the mean clinical scores (presence of scabs/crusts) decreased from 3.48, 3.37, 3.43 and 3.45 to 0.37, 0.42, 0.78 and 0.38 in the ears of animals in groups A, B , C and D, respectively, which were similar to the observations recorded in the positive control rabbits. However, the clinical score for negative control rabbits did not increase significantly (P > 0.05) during the experiment, and this changed from 3.32 to 3.37 in the ears, and there were no significant differences in clinical efficacy between left and right ears. After two treatments (0 and 7 d), the rabbits in groups A, B, C and D had recovered completely 14 days after the last treatment and no recurrences of infection were observed. CONCLUSIONS: These results indicate that euptox A was potent compounds for the effective control of animal P. cuniculi in vivo

Integrated bioinformatics identifies key mediators in cytokine storm and tissue remodeling during Vibrio mimicus infection in yellow catfish (Pelteobagrus fulvidraco)

IntroductionThe pathogenesis of Vibrio mimicus infection in yellow catfish (Pelteobagrus fulvidraco) remains poorly understood, particularly regarding the impact of infection with the pathogen on primary target organs such as the skin and muscle.MethodsIn this study, we aim to analyze the pathological intricacies of the skin and muscle of yellow catfish after being infected with V. mimicus using a 1/10 LC50 seven-day post-infection model. Furthermore, we have utilized integrated bioinformatics to comprehensively elucidate the regulatory mechanisms and identify the key regulatory genes implicated in this phenomenon.ResultsOur histopathological examination revealed significant pathological changes in the skin and muscle, characterized by necrosis and inflammation. Moreover, tissue remodeling occurred, with perimysium degeneration and lesion invasion into the muscle along the endomysium, accompanied by a transformation of type I collagen into a mixture of type I and type III collagens in the perimysium and muscle bundles. Our eukaryotic transcriptomic and 4D label-free analyses demonstrated a predominantly immune pathway response in both the skin and muscle, with downregulation observed in several cell signaling pathways that focused on focal adhesion-dominated cell signaling pathways. The upregulated genes included interleukins (IL)-1 and -6, chemokines, and matrix metallopeptidases (mmp)-9 and -13, while several genes were significantly downregulated, including col1a and col1a1a. Further analysis revealed that these pathways were differentially regulated, with mmp-9 and mmp-13 acting as the potential core regulators of cytokine and tissue remodeling pathways. Upregulation of NF-κB1 and FOSL-1 induced by IL-17C and Nox 1/2-based NADPH oxidase may have held matrix metallopeptidase and cytokine-related genes. Also, we confirmed these relevant regulatory pathways by qPCR and ELISA in expanded samples.DiscussionOur findings unequivocally illustrate the occurrence of a cytokine storm and tissue remodeling, mediated by interleukins, chemokines, and MMPs, in the surface of yellow catfish infected with V. mimicus. Additionally, we unveil the potential bidirectional regulatory role of MMP-9 and MMP-13. These results provide novel perspectives on the intricate immune response to V. mimicus infection in yellow catfish and highlight potential targets for developing therapies

Sodium Fluoride Arrests Renal G2/M Phase Cell-Cycle Progression by Activating ATM-Chk2-P53/Cdc25C Signaling Pathway in Mice

Background/Aims: Excessive fluoride intake can induce cytotoxicity, DNA damage and cell-cycle changes in many tissues and organs, including the kidney. However, the underlying molecular mechanisms of fluoride-induced renal cell-cycle changes are not well understood at present. In this study, we used a mouse model to investigate how sodium fluoride (NaF) induces cell-cycle changes in renal cells. Methods: Two hundred forty ICR mice were randomly assigned to four equal groups for intragastric administration of NaF (0, 12, 24 and 48 mg/kg body weight/day) for 42 days. Kidneys were taken to measure changes of the cell-cycle at 21 and 42 days of the experiment, using flow cytometry, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot methods. Results: NaF, at more than 12 mg/kg body weight, induced G2/M phase cell-cycle arrest in the renal cells, which was supported by the finding of significantly increased percentages of renal cells in the G2/M phase. We found also that G2/M phase cell-cycle arrest was accompanied by up-regulation of p-ATM, p-Chk2, p-p53, p-Cdc25C, p-CDK1, p21, and Gadd45a protein expression levels; up-regulation of ATM, Chk2, p53, p21, and Gadd45a mRNA expression levels; down-regulation of CyclinB1, mdm2, PCNA protein expression levels; and down-regulation of CyclinB1, CDK1, Cdc25C, mdm2, and PCNA mRNA expression levels. Conclusion: In this mouse model, NaF, at more than 12 mg/ kg, induced G2/M phase cell-cycle arrest by activating the ATM-Chk2-p53/Cdc25C signaling pathway, which inhibits the proliferation of renal cells and development of the kidney. Activation of the ATM-Chk2-p53/Cdc25C signaling pathway is the mechanism of NaF-induced renal G2/M phase cell-cycle arrest in this model

Altered fecal microbiome and correlations of the metabolome with plasma metabolites in dairy cows with left displaced abomasum

Left displaced abomasum (LDA) in postpartum dairy cows contributes to significant economic losses. Dairy cows with LDA undergo excessive lipid mobilization and insulin resistance. Although gut dysbiosis is implicated, little is known about the role of the gut microbiota in the abnormal metabolic processes of LDA. To investigate the functional links among microbiota, metabolites, and disease phenotypes in LDA, we performed 16S rDNA gene amplicon sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS) of fecal samples from cows with LDA (n = 10) and healthy cows (n = 10). Plasma marker profiling was synchronously analyzed. In the LDA event, gut microbiota composition and fecal metabolome were shifted in circulation with an amino acid pool deficit in dairy cows. Compared with the healthy cows, salicylic acid derived from microbiota catabolism was decreased in the LDA cows, which negatively correlated with Akkermansia, Prevotella, non-esterified fatty acid (NEFA), and β-hydroxybutyric acid (BHBA) levels. Conversely, fecal taurolithocholic acid levels were increased in cows with LDA. Based on integrated analysis with the plasma metabolome, eight genera and eight metabolites were associated with LDA. Of note, the increases in Akkermansia and Oscillospira abundances were negatively correlated with the decreases in 4-pyridoxic acid and cytidine levels, and positively correlated with the increases in NEFA and BHBA levels in amino acid deficit, indicating pyridoxal metabolism-associated gut dysbiosis and lipolysis. Changes in branched-chain amino acids implicated novel host-microbial metabolic pathways involving lipolysis and insulin resistance in cows with LDA. Overall, these results suggest an interplay between host and gut microbes contributing to LDA pathogenesis

Development and evaluation of a loop-mediated isothermal amplification (LAMP) assay for rapid detection of Actinobacillus pleuropneumoniae based the dsbE-like gene

This paper reports on the development and validation of a loop-mediated isothermal amplification assay (LAMP) for the rapid and specific detection of Actinobacillus pleuropneumoniae (A. pleuropneumoniae). A set of six primers were designed derived from the dsbE-like gene of A.pleuropneumoniae and validate the assay using 9 A. pleuropneumoniae reference/field strains, 132 clinical isolates and 9 other pathogens. The results indicated that positive reactions were confirmed for all A. pleuropneumoniae strains and specimens by LAMP at 63ºC for 60 min and no cross-reactivity were observed from other non-A.pleuropneumoniae including Haemophilus parasuis, Escherichia coli, Pasteurella multocida, Bordetella bronchiseptica, Streptococcus suis, Salmonella enterica, Staphylococcus, porcine reproductive and respiratory syndrome virus (PRRSV), and Pseudorabies virus. The detection limit of the conventional PCR was 10² CFU per PCR test tube, while that of the LAMP was 5 copies per tube. Therefore, the sensitivity of LAMP was higher than that of PCR. Moreover, the LAMP assay provided a rapid yet simple test of A. pleuropneumoniae suitable for laboratory diagnosis and pen-side detection due to ease of operation and the requirement of only a regular water bath or heat block for the reaction

Development and validation of HERWIG 7 tunes from CMS underlying-event measurements

This paper presents new sets of parameters (“tunes”) for the underlying-event model of the HERWIG7 event generator. These parameters control the description of multiple-parton interactions (MPI) and colour reconnection in HERWIG7, and are obtained from a fit to minimum-bias data collected by the CMS experiment at s=0.9, 7, and 13Te. The tunes are based on the NNPDF 3.1 next-to-next-to-leading-order parton distribution function (PDF) set for the parton shower, and either a leading-order or next-to-next-to-leading-order PDF set for the simulation of MPI and the beam remnants. Predictions utilizing the tunes are produced for event shape observables in electron-positron collisions, and for minimum-bias, inclusive jet, top quark pair, and Z and W boson events in proton-proton collisions, and are compared with data. Each of the new tunes describes the data at a reasonable level, and the tunes using a leading-order PDF for the simulation of MPI provide the best description of the dat

Search for top squark pair production using dilepton final states in pp collision data collected at root s=13TeV

A search is presented for supersymmetric partners of the top quark (top squarks) in final states with two oppositely charged leptons (electrons or muons), jets identified as originating from bquarks, and missing transverse momentum. The search uses data from proton-proton collisions at root s = 13 TeV collected with the CMS detector, corresponding to an integrated luminosity of 137 fb(-1). Hypothetical signal events are efficiently separated from the dominant top quark pair production background with requirements on the significance of the missing transverse momentum and on transverse mass variables. No significant deviation is observed from the expected background. Exclusion limits are set in the context of simplified supersymmetric models with pair-produced lightest top squarks. For top squarks decaying exclusively to a top quark and a lightest neutralino, lower limits are placed at 95% confidence level on the masses of the top squark and the neutralino up to 925 and 450 GeV, respectively. If the decay proceeds via an intermediate chargino, the corresponding lower limits on the mass of the lightest top squark are set up to 850 GeV for neutralino masses below 420 GeV. For top squarks undergoing a cascade decay through charginos and sleptons, the mass limits reach up to 1.4 TeV and 900 GeV respectively for the top squark and the lightest neutralino.Peer reviewe

Measurement of the t(t)over-barb(b)over-bar production cross section in the all-jet final state in pp collisions at root s=13 TeV

A measurement of the production cross section of top quark pairs in association with two b jets (t (t) over barb (b) over bar) is presented using data collected in proton-proton collisions at root s=13 TeV by the CMS detector at the LHC corresponding to an integrated luminosity of 35.9 fb(-1). The cross section is measured in the all-jet decay channel of the top quark pair by selecting events containing at least eight jets, of which at least two are identified as originating from the hadronization of b quarks. A combination of multivariate analysis techniques is used to reduce the large background from multijet events not containing a top quark pair, and to help discriminate between jets originating from top quark decays and other additional jets. The cross section is determined for the total phase space to be 5.5 +/- 0.3 (stat)(-1.3)(+)(1.6) (syst)pb and also measured for two fiducial t (t) over barb (b) over bar, definitions. The measured cross sections are found to be larger than theoretical predictions by a factor of 1.5-2.4, corresponding to 1-2 standard deviations. (C) 2020 The Author. Published by Elsevier B.V.Peer reviewe

Measurement of the W gamma Production Cross Section in Proton-Proton Collisions at root s=13 TeV and Constraints on Effective Field Theory Coefficients

A fiducial cross section for W gamma production in proton-proton collisions is measured at a center-of-mass energy of 13 TeV in 137 fb(-1) of data collected using the CMS detector at the LHC. The W -> e nu and mu nu decay modes are used in a maximum-likelihood fit to the lepton-photon invariant mass distribution to extract the combined cross section. The measured cross section is compared with theoretical expectations at next-to-leading order in quantum chromodynamics. In addition, 95% confidence level intervals are reported for anomalous triple-gauge couplings within the framework of effective field theory.Peer reviewe

Search for supersymmetry in final states with photons and missing transverse momentum in proton-proton collisions at 13 TeV

Results are reported of a search for supersymmetry in final states with photons and missing transverse momentum in proton-proton collisions at the LHC. The data sample corresponds to an integrated luminosity of 35.9 fb collected at a center-of-mass energy of 13 TeV using the CMS detector. The results are interpreted in the context of models of gauge-mediated supersymmetry breaking. Production cross section limits are set on gluino and squark pair production in this framework. Gluino masses below 1.86 TeV and squark masses below 1.59 TeV are excluded at 95% confidence levelIndividuals have received support from the Marie-Curie program and the European Research Council and Horizon 2020 Grant, contract No. 675440 (European Union); the Leventis Foundation; the A.P. Sloan Foundation; the Alexander von Humboldt Foundation; the Belgian Federal Science Policy Office; the Fonds pour la Formation a la Recherche dans l’Industrie et dans l’Agriculture (FRIA-Belgium); the Agentschap voor Innovatie door Wetenschap en Technologie (IWT-Belgium); the F.R.S.-FNRS and FWO (Belgium) under the “Excellence of Science — EOS” — be.h project n. 30820817; the Ministry of Education, Youth and Sports (MEYS) of the Czech Republic; the Lendület (“Momentum”) Program and the J´anos Bolyai Research Scholarship of the Hungarian Academy of Sciences, the New National Excellence Program UNKP, the NKFIA research grants 123842, 123959, 124845, 124850 and 125105 (Hungary); the Council of Science and Industrial Research, India; the HOMING PLUS program of the Foundation for Polish Science, cofinanced from European Union, Regional Development Fund, the Mobility Plus program of the Ministry of Science and Higher Education, the National Science Center (Poland), contracts Harmonia 2014/14/M/ST2/00428, Opus 2014/13/B/ST2/02543, 2014/15/B/ST2/03998, and 2015/19/B/ST2/02861, Sonata-bis 2012/07/E/ST2/01406; the National Priorities Research Program by Qatar National Research Fund; the Programa Estatal de Fomento de la Investigación Científica y Técnica de Excelencia María de Maeztu, grant MDM-2015-0509 and the Programa Severo Ochoa del Principado de Asturias; the Thalis and Aristeia programs cofinanced by EU-ESF and the Greek NSRF; the Rachadapisek Sompot Fund for Postdoctoral Fellowship, Chulalongkorn University and the Chulalongkorn Academic into Its 2nd Century Project Advancement Project (Thailand); the Welch Foundation, contract C-1845; and the Weston Havens Foundation (U.S.A.)