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Abstract Background Toxoplasma gondii is an important protozoan pathogen with medical and veterinary importance worldwide. Drugs currently used for treatment of toxoplasmosis are less effective and sometimes cause serious side effects. There is an urgent need for the development of more effective drugs with relatively low toxicity. Methods The effect of tylosin on the viability of host cells was measured using CCK8 assays. To assess the inhibition of tylosin on T. gondii proliferation, a real-time PCR targeting the B1 gene was developed for T. gondii detection and quantification. Total RNA was extracted from parasites treated with tylosin and then subjected to transcriptome analysis by RNA sequencing (RNA-seq). Finally, murine infection models of toxoplasmosis were used to evaluate the protective efficacy of tylosin against T. gondii virulent RH strain or avirulent ME49 strain. Results We found that tylosin displayed low host toxicity, and its 50% inhibitory concentration was 175.3 μM. Tylsoin also inhibited intracellular T. gondii tachyzoite proliferation, with a 50% effective concentration of 9.759 μM. Transcriptome analysis showed that tylosin remarkably perturbed the gene expression of T. gondii, and genes involved in “ribosome biogenesis (GO:0042254)” and “ribosome (GO:0005840)” were significantly dys-regulated. In a murine model, tylosin treatment alone (100 mg/kg, i.p.) or in combination with sulfadiazine sodium (200 mg/kg, i.g.) significantly prolonged the survival time and raised the survival rate of animals infected with T. gondii virulent RH or avirulent ME49 strain. Meanwhile, treatment with tylosin significantly decreased the parasite burdens in multiple organs and decreased the spleen index of mice with acute toxoplasmosis. Conclusions Our findings suggest that tylosin exhibited potency against T. gondii both in vitro and in vivo, which offers promise for treatment of human toxoplasmosis. Graphical Abstract

Abstract Aiming at the problem of distributed target detection when there is signal mismatch, this paper proposes a tunable detector, which is characterised by a tunable parameter. The proposed detector can realise the flexible detection of mismatch signals by adjusting the tunable parameter, and hence the directivity (robustness or selectivity to mismatched signals) of the tunable detector can be smoothly adjusted. In addition, the tunable detector can obtain approximately the same detection performance as the corresponding generalised likelihood ratio test in the absence of signal mismatch. The proposed tunable detector also possesses the constant false alarm rate property. Numerical examples illustrate the effectiveness of the proposed detector.

BACKGROUND: The whitefly Bemisa tabaci is a species complex of more than 31 cryptic species which include some of the most destructive invasive pests of crops worldwide. Among them, Middle East-Asia Minor 1 (MEAM1) and Mediterranean have invaded many countries and displaced the native whitefly species. The successful invasion of the two species is largely due to their wide range of host plants, high resistance to insecticides and remarkable tolerance to environmental stresses. However, the molecular differences between invasive and indigenous whiteflies remain largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here the global transcriptional difference between the two invasive whitefly species (MEAM1, MED) and one indigenous whitefly species (Asia II 3) were analyzed using the Illumina sequencing. Our analysis indicated that 2,422 genes between MEAM1 and MED; 3,073 genes between MEAM1 and Asia II 3; and 3,644 genes between MED and Asia II 3 were differentially expressed. Gene Ontology enrichment analysis revealed that the differently expressed genes between the invasive and indigenous whiteflies were significantly enriched in the term of 'oxidoreductase activity'. Pathway enrichment analysis showed that carbohydrate, amino acid and glycerolipid metabolisms were more active in MEAM1 and MED than in Asia II 3, which may contribute to their differences in biological characteristics. Our analysis also illustrated that the majority of genes involved in 'drug metabolic pathway' were expressed at a higher level in MEAM1 and MED than in Asia II 3. Taken together, these results revealed that the genes related to basic metabolism and detoxification were expressed at an elevated level in the invasive whiteflies, which might be responsible for their higher resistance to insecticides and environmental stresses. CONCLUSIONS/SIGNIFICANCE: The extensive comparison of MEAM1, MED and Asia II 3 gene expression may serve as an invaluable resource for revealing the molecular mechanisms underlying their biological differences and the whitefly invasion.

The effective plugging of artificial fractures is key to the success of temporary plugging and diverting fracturing technology, which is one of the most promising ways to improve the heat recovery efficiency of hot dry rock. At present, how temporary plugging agents plug artificial fractures under high temperature remains unclear. In this paper, by establishing an improved experimental system for the evaluation of temporary plugging performance at high temperature, we clarified the effects of high temperature, injection rate, and fracture width on the pressure response and plugging efficiency of the fracture. The results revealed that the temporary plugging process of artificial fractures in hot dry rock can be divided into four main stages: the initial stage of temporary plugging, the bridging stage of the particles, the plugging formation stage, and the high-pressure dense plugging stage. As the temperature increases, the distribution distance of the temporary plugging agent, the number of pressure fluctuations, and the time required for crack plugging increases. Particularly, when the temperature increases by 100 °C, the complete plugging time increases by 90.7%. [ABSTRACT FROM AUTHOR]

Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and progressive external ophthalmoplegia (PEO) are established phenotypes of mitochondrial disorders. They are maternally-inherited, multisystem disorder that is characterized by variable clinical, biochemical, and imaging features. We described the clinical and genetic features of a Chinese patient with late-onset MELAS/PEO overlap syndrome, which has rarely been reported. The patient was a 48-year-old woman who presented with recurrent ischemic strokes associated with characteristic brain imaging and bilateral ptosis. We assessed her clinical characteristics and performed mutation analyses. The main manifestations of the patient were stroke-like episodes and seizures. A laboratory examination revealed an increased level of plasma lactic acid and a brain MRI showed multiple lesions in the cortex. A muscle biopsy demonstrated ragged red fibers. Genetic analysis from a muscle sample identified two mutations: TL1m.3243A>G and POLG c.3560C>T, with mutation loads of 83 and 43%, respectively. This suggested that mitochondrial disorders are associated with various clinical presentations and an overlap between the syndromes and whole exome sequencing is important, as patients may carry multiple mutations. [ABSTRACT FROM AUTHOR]

Introduction. The aim of the study was to investigate the clinical significance of Ly-1 antibody reactive clone (LYAR) in non-small-cell lung cancer (NSCLC). Material and methods. The expressions of LYAR at the protein level in representative paired NSCLC tumor tissues and adjacent non-tumor tissues were measured by Western blot and immunohistochemistry. Kaplan-Meier method was used to calculate the survival curve of patients with NSCLC. Cell Counting Kit-8 assay and flow cytometry were used to estimate the cell proliferation and cell cycle, respectively. Terminal-deoxynucleotidyl-transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay was performed to detect cell apoptosis. Results. LYAR was dramatically overexpressed in NSCLC tissues which were closely related to the survival of patients with NSCLC. In clinical studies, the expression of LYAR was related to the clinical stage, histological differentiation, and Ki-67 expression. A positive correlation was found between LYAR and Ki-67 expression by Spearman's correlation test. After serum starvation for 72 h, serum re-addition significantly increased the expression of LYAR, PCNA, and Cyclin A and promoted the cell cycle progression. LYAR knockdown inhibited the proliferation and induced the G0/G1 cell cycle arrest and apoptosis of A549 cells. Conclusions. The present study revealed the clinical significance of LYAR in NSCLC. LYAR might serve as a tumor promoter in NSCLC progression by promoting the proliferation and inhibiting the apoptosis of NSCLC cells. Inhibiting the expression of LYAR was considered as a potential novel therapeutic strategy for NSCLC. [ABSTRACT FROM AUTHOR]

A new species of Diogenes Dana, 1851, Diogenes bispinatus sp. nov., is described from the South China Sea. It is closely allied to Diogenes dorotheae Morgan & Forest, 1991 and D. patae Asakura & Godwin, 2006, but it morphologically differs from the latter in the length of the antennular peduncle, the number of spines on the ocular acide, the shape of the antennal acide and the number of spines, the shape of the palm of left cheliped and telson. A key to the species of Diogenes from China seas is provided. [ABSTRACT FROM AUTHOR]

Background Cardiac dysfunction in diabetic cardiomyopathy may be associated with abnormal Ca2+ homeostasis. This study investigated the effects of alterations in Ca2+ homeostasis and sarcoplasmic reticulum Ca2+-associated proteins on cardiac function in the development of diabetic cardiomyopathy. Methods Sprague-Dawley rats were divided into 4 groups (n = 12, each): a control group, and streptozotocin-induced rat models of diabetes groups, examined after 4, 8, or 12 weeks. Evaluations on cardiac structure and function were performed by echocardiography and hemodynamic examinations, respectively. Cardiomyocytes were isolated and spontaneous Ca2+ spark images were formed by introducing fluorescent dye Fluo-4 and obtained with confocal scanning microscopy. Expressions of Ca2+-associated proteins were assessed by Western blotting. Results Echocardiography and hemodynamic measurements revealed that cardiac dysfunction is associated with the progression of diabetes, which also correlated with a gradual but significant decline in Ca2+ spark frequency (in the 4-, 8- and 12-week diabetic groups). However, Ca2+ spark decay time constants increased significantly, relative to the control group. Expressions of ryanodine receptor 2 (RyR2), sarcoplasmic reticulum Ca2+-2ATPase (SERCA) and Na +/Ca 2+ exchanger (NCX1) were decreased, together with quantitative alterations in Ca2+regulatory proteins, FKBP12.6 and phospholamban progressively and respectively in the diabetic rats. Conclusions Ca2+ sparks exhibited a time-dependent decay with progression of diabetic cardiomyopathy, which may partly contribute to cardiac dysfunction. This abnormality may be attributable to alterations in the expressions of some Ca2+-associated proteins. [ABSTRACT FROM AUTHOR]

For along-track multichannel synthetic aperture radar, this paper proposes a novel ground moving target signal model in the high-resolution complex image domain. Based on the range-Doppler imaging of static scene, the 2-D complex response of an isolated rectilinearly moving target is derived via the stationary phase principle (SPP) approximations. It is shown that moving targets in complex domain can be divided into three types according to the 2-D motion distribution and the SPP approximation conditions. Different from the known peaklike response of a static target, different amplitude and phase modulations will appear for different types of moving targets. Moreover, a single target can be split into two targets in the image when its Doppler spectrum spreads over two ambiguous Doppler zones. All types of targets will have the same Doppler interferometric effect along multichannel images, which is decided by the target's ambiguous Doppler frequency. Furthermore, with the proposed signal model, the complex image properties can be completely described and analyzed. Finally, some numerical experiments are also provided to demonstrate the effectiveness of the proposed signal model and analysis. [ABSTRACT FROM AUTHOR]

Based on a parametric model and some optimum methods, it has been previously proved that parametric velocity synthetic aperture radar (VSAR) may improve the performances of moving target detection and parameter estimation simultaneously. In this paper, multilook processing is studied for parametric VSAR. At first, statistical signal models are established for azimuth multilook processing (AMLP) and range multilook processing (RMLP), respectively. By combining the multiple AMLP sublook pixel vectors, it is shown that the clutter parameter estimation accuracy can be further improved via the maximum- likelihood estimation methods. Meanwhile, based on the adaptive implementation for the optimum processing of VSAR, RMLP can be used to improve slowly moving target detection performance via the noncoherent integration of multiple range sublooks. Furthermore, it is shown that the Doppler frequencies of moving targets vary linearly with different range sublooks due to the different carrier frequencies of sublooks. Therefore, based on a proposed novel two-step multilook diversity (TS-MLD) estimator for RMLP, the "azimuth location ambiguity" of VSAR can be well resolved via least squares linear regression, without configuration change of the conventional VSAR. Also, the estimation accuracy of target's unambiguous Doppler frequency, as well as target's azimuth location, is derived for the proposed TS-MLD method. Finally, numerical experiments and scene simulations are provided to demonstrate the effectiveness of the proposed multilook-based methods. [ABSTRACT FROM AUTHOR]

Velocity synthetic aperture radar (VSAR) is equipped with a linear array to receive the echoes from a radar illuminating area via multiple channels, each of which can reconstruct a reflectivity image for the same stationary scene. Based on analysis of pixel vector sampled among multi-images, VSAR may effectively suppress the strong ground clutter and improve moving target detection and location. In this paper, different Doppler-distributed properties are derived for the moving target and clutter, respectively. Then, we propose a novel parametric statistical model for VSAR by dividing the pixel vector into three components, namely, target, clutter, and noise. Furthermore, a method of adaptive implementation of optimal processing (AIOP-VSAR) is presented for moving target detection. It is shown that the optimum detection performance may be obtained via AIOP-VSAR, particularly for the slowly moving target in an inhomogeneous clutter environment. Also, the Cramer-Rao bounds (CRBs) are derived for the estimation of unknown model parameters, as well as the azimuth locations of moving targets, and the maximum-likelihood methods are proposed to reach these CRBs. Based on the proposed target detection and parameter estimation methods, we present a complete parametric flowchart for VSAR. It is demonstrated that the proposed flowchart may effectively mitigate the "azimuth location ambiguity" of VSAR and has the super-resolution ability to resolve "velocity layover" for multiple targets. Finally, some detailed numerical experiments and scene simulations are provided to show the effectiveness of the proposed methods. [ABSTRACT FROM AUTHOR]

Purpose ? It is well known that precision of mass unbalance measurement of sphere is determined by perturbing moments in contactless suspension systems. Therefore, estimating perturbing moment level in those systems is important and necessary to meet the requirements of a specified precision of mass unbalance measurement. Design/methodology/approach ? In this paper, probability-theoretic method is employed to determine probability characteristics of the perturbing moments in both electrostatic suspension system and gas suspension system by statistically estimating of the quality of sphere surface. As a result, the relationship between probability characteristics of the perturbing moment and statistical estimates of the quality of sphere surface is established. It is expressed as a simple formula by specifying the correlation function of random field of sphere surface. Findings ? Numerical experiments of the perturbing moment calculation in the two suspension systems show that for sphere with small correlation coefficient a, it is better to use gas suspension system for mass unbalance measurement. While for sphere with large correlation coefficient a, electrostatic suspension system is more suitable for its perturbing moment are less than gas suspension system. Originality/value ? Knowledge of this relationship is of great theoretic and practical importance, since the probabilistic depiction of the perturbing moments, and hence the accuracy of the mass unbalance measurement systems can be estimated without a detailed roundness measurement of the sphere surface. [ABSTRACT FROM AUTHOR]

High-voltage amplifiers as a means of amplifying the low-output voltage signals of the feedback controllers to the suspension voltages typically in the kilovolts range are often required for electrostatic force generation in electrostatic levitation. This paper proposes a high-voltage dc amplifier including an amplitude modulator, a power amplifier, a step-up transformer, a pair of peak detectors, and a voltage feedback channel to stabilize the amplifier outputs in an effort to provide high suspension voltage and fast dynamic response. Since the various carrier frequencies have virtually no effect on the power consumption of the dc amplifier by filtering out the high-frequency carrier components with peak detectors while keeping the input signal unaffected, satisfactory dynamic performance can be achieved by choosing a sufficiently high carrier frequency. The operating principle of the dc amplifier is analyzed, followed by an experimental performance evaluation and discussion for electrostatic levitation applications. The experimental results demonstrate the superiority of the high-voltage dc amplifier over classical ac amplifiers in terms of dynamic response, force-voltage coefficient, voltage ripple, power consumption, and long-time stability using a carrier frequency of 30 kHz and the closed-loop control scheme. [ABSTRACT FROM AUTHOR]

Presents a study which reported a space-time adaptive processing (STAP) approach using the multiple-beam and multiple Doppler channels for airborne phased array radar. Method used in realizing the adaptivity of STAP processor to the nonhomogenous clutter environments; Performance of STAP in an Earth-clutter environment.

The differential quadrature (DQ) element method proposed by Wang and Gu in 1997 has been extended to analyse rectangular plate problems. The methodology is worked out in detail and some numerical examples are given. Copyright © 1998 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Fetal magnetocardiography (MCG) is a sophisticated non-invasive technique for the fetal heart diagnosis. We constructed a multichannel fetal MCG system based on a novel superconducting quantum interference device (SQUID) direct readout scheme called SQUID bootstrap circuit (SBC). The system incorporates four SBC gradiometers for the signal detection and three SBC magnetometers as the references. The fetal MCG signal at a 28-weeks' gestation was measured. By the fetal MCG signal separation and average, the P-wave and QRS complex can be clearly identified. These results indicate that the SBC is one of the most promising techniques for the fetal MCG recordings. [ABSTRACT FROM AUTHOR]

Abstract Background Multidrug resistance in Enterobacteriaceae including resistance to quinolones is rising worldwide. The development of resistance may lead to the emergence of new transmission mechanisms. In this study, the collection of different E. coli was performed from animals and subjected to subsequent procedures including pulsed-field gel electrophoresis, micro-broth dilution method, polymerase chain reaction. Whole genome sequencing of E. coli C3 was performed to detect the affinity, antimicrobial resistance and major carriers of the isolates. Results A total of 66 E. coli were isolated and their antibiotic resistance genes, frequency of horizontal transfer and genetic environment of E. coli C3 were determined. The results showed there were both different and same types in PFGE typing, indicating clonal transmission of E. coli among different animals. The detection of antimicrobial resistance and major antibiotic resistance genes and the plasmid transfer results showed that strains from different sources had high levels of resistance to commonly used clinical antibiotics and could be spread horizontally. Whole-genome sequencing discovered a novel ICE mobile element. Conclusion In summary, the antimicrobial resistance of E. coli in northeast China is a serious issue and there is a risk of antimicrobial resistance transmission. Meanwhile, a novel ICE mobile element appeared in the process of antimicrobial resistance formation.

A dual-washer superconducting quantum interference device (SQUID) with a loop inductance of 350 pH and two on-washer integrated input coils is designed according to conventional niobium technology. In order to obtain a large SQUID flux-to-voltage transfer coefficient, the junction shunt resistance is selected to be 33 Ω. A vertical SQUID gradiometer module with a baseline of 100 mm is constructed by utilizing such a SQUID and a first-order niobium wire-wound antenna. The sensitivity of this module reaches about 0.2 fT/(cm·Hz1/2) in the white noise range using a direct readout scheme, i.e., the SQUID is directly connected to an operational amplifier, in a magnetically shielded room. Some magnetocardiography (MCG) measurements with a sufficiently high signal-to-noise ratio (SNR) are demonstrated. [ABSTRACT FROM AUTHOR]

Skeletal muscle regeneration is essential for maintaining muscle function in injury and muscular disease. Myogenesis plays key roles in forming new myofibers during the process. Here, through bioinformatic screen for the potential regulators of myogenesis from 5 independent microarray datasets, we identify an overlapping differentially expressed gene (DEG) optineurin (OPTN). Optn knockdown (KD) delays muscle regeneration in mice and impairs C2C12 myoblast differentiation without affecting their proliferation. Conversely, Optn overexpression (OE) promotes myoblast differentiation. Mechanistically, OPTN increases nuclear levels of β-catenin and enhances the T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription activity, suggesting activation of Wnt signaling pathway. The activation is accompanied by decreased protein levels of glycogen synthase kinase 3β (GSK3β), a negative regulator of the pathway. We further show that OPTN physically interacts with and targets GSK3β for autophagic degradation. Pharmacological inhibition of GSK3β rescues the impaired myogenesis induced by Optn KD during muscle regeneration and myoblast differentiation, corroborating that GSK3β is the downstream effector of OPTN-mediated myogenesis. Together, our study delineates the novel role of OPTN as a potential regulator of myogenesis and may open innovative therapeutic perspectives for muscle regeneration.

Reduced-pressure electron beam (EB) plate butt welds were manufactured in two low-alloy pressure-vessel steels, SA508 Gr 3 Cl 1 and SA508 Gr 2, at two thicknesses in both steels, 30 mm and 130 mm. Transient temperatures during welding were recorded using thermocouple arrays. Residual stresses in the as-welded condition and after post-weld heat treatment were measured using diverse methods: neutron diffraction and the contour method at 30 mm thickness; and deep hole drilling and the contour method at 130 mm. Incremental centre hole drilling measurements were performed at 130 mm thickness to better understand near-surface stresses. Weld and heat-affected zone microstructures and microconstituents were evaluated using a combination of hardness mapping, optical microscopy and electron microscopy. The as-welded residual stresses exhibit the characteristic M-shaped distribution for hardenable steels, reaching 500–600 MPa in tension in both steels at both thicknesses. However, the modest changes to the chemical composition and the change in plate thickness both significantly influenced microstructures, mechanical properties and residual stress distributions. These sensitivities underline the need for physically faithful models. This extensive characterisation study enables the development and validation of models that predict the development of microstructures and residual stresses in EB welds in low alloy pressure vessel steels.

The prevalence of obesity has increased dramatically worldwide in the past ~50 years. Searching for safe and effective anti-obesity strategies are urgently needed. Lactucin, a plant-derived natural small molecule, is known for anti-malaria and anti-hyperalgesia. The study is to investigate whether lactucin plays a key role in adipogenesis. To this end, in vivo male C57BL/6 mice fed a high-fat diet (HFD) were treated with 20 mg/kg/day of lactucin or vehicle by gavage for seven weeks. Compared with vehicle-treated controls, Lactucin-treated mice showed lower body mass and mass of adipose tissue. Consistently, in vitro 3T3-L1 cells were treated with 20 μM of lactucin. Compared to controls, lactucin-treated cells showed significantly less lipid accumulation during adipocyte differentiation and lower levels of lipid synthesis markers. Mechanistically, we showed the anti-adipogenic property of lactucin was largely limited to the early stage of adipogenesis. Lactucin-treated cells fail to undergo mitotic clonal expansion (MCE). Further studies demonstrate that lactucin-induced MCE arrests might result from reduced phosphorylation of JAK2 and STAT3. We then asked whether activation of JAK2/STAT3 would restore the inhibitory effect of lactucin on adipogenesis with pharmacological STAT3 activator colivelin. Our results revealed similar levels of lipid accumulation between lactucin-treated cells and controls in the presence of colivelin, indicating that inactivation of STAT3 is the limiting factor for the anti-adipogenesis of lactucin in these cells. Together, our results provide the indication that lactucin exerts an anti-adipogenesis effect, which may open new therapeutic options for obesity.

The begomoviruses are the largest and most economically important group of plant viruses transmitted exclusively by the whitefly Bemisia tabaci in a circulative, persistent manner. The circulation of the viruses within the insect vectors involves complex interactions between virus and vector components; however, the molecular mechanisms of these interactions remain largely unknown. Here we investigated the transcriptional response of the invasive B. tabaci Middle East-Asia Minor 1 species to Tomato yellow leaf curl China virus (TYLCCNV) using Illumina sequencing technology. Results showed that 1,606 genes involved in 157 biochemical pathways were differentially expressed in the viruliferous whiteflies. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that TYLCCNV can perturb the cell cycle and primary metabolism in the whitefly, which explains the negative effect of this virus on the longevity and fecundity of B. tabaci. Our data also demonstrated that TYLCCNV can activate whitefly immune responses, such as autophagy and antimicrobial peptide production, which might lead to a gradual decrease of viral particles within the body of the viruliferous whitefly. Furthermore, PCR results showed that TYLCCNV can invade the ovary and fat body tissues of the whitefly, and Lysotracker and Western blot analyses revealed that the invasion of TYLCCNV induced autophagy in both the ovary and fat body tissues. Surprisingly, TYLCCNV also suppressed the whitefly immune responses by downregulating the expression of genes involved in Toll-like signaling and mitogen-activated protein kinase (MAPK) pathways. Taken together, these results reveal the relationship of coevolved adaptations between begomoviruses and whiteflies and will provide a road map for future investigations into the complex interactions between plant viruses and their insect vectors. [ABSTRACT FROM AUTHOR]