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We formulate an SEIR model for information propagation with the effect of a hot search in complex networks. Mathematical analysis is conducted in both a homogeneous network and heterogenous network. The results reveal that the dynamics are completely determined by the basic propagation number if the effect of a hot search is absent. On the other hand, when the effect of a hot search is taken into account, there exists no information-free equilibrium, and the information-propagating equilibrium is stable if the threshold is greater than 1. Numerical simulations were performed to examine the sensitivity of the parameters to the basic propagation number and the propagable nodes. Furthermore, the proposed model has been applied to fit the collected data for two types of information spreading in Sina Weibo, which confirmed the validity of our model and simulated the dynamical behaviors of information propagation.

The purpose of this paper is to investigate the impact of the varying population sizes on the dynamic behavior of the age-structured epidemic model. A age-structured SIRS epidemic model with the varying population sizes is established and investigated to take into account time delay. The non-negativity of the solution, the existence and stability of the steady states, and the existence of the Hopf bifurcation are discussed. The numerical simulations show that the varying population sizes can cause the age-structured SIRS model to produce multiple stability switches.

In this paper, considering the mooring system can be taut-slack in the motion, the dynamic equations of the mooring system are derived by using the theory of large deformation. The nonlinear dynamic response of semitensioned mooring line is numerically simulated. Assuming the platform motion is known, the effect of platform on mooring line is simplified as an end-point excitation. Directly using the finite difference method for numerically solving partial differential equations of mooring line, the dynamic responses can be obtained. Then, the causes about the nonlinear state are analyzed, and the location where the taut-slack phenomenon occurs can be located by calculating the tension of mooring. The results show that the mooring line is more likely to be taut-slack under tangential excitation with the tension change, while the mooring remains taut under normal excitation. The taut-slack state of the mooring line is concentrated near the anchor point. Through the amplitude-frequency curve and bifurcation point set, it is found that the taut-slack region is accompanied by multiperiod motion. And the taut-slack phenomenon will lead to the unstable motion.

Fluorescence polarization immunoassay (FPIA) is a homogeneous and rapid analytical method that is suitable for high-throughput screening of large numbers of samples. However, FPIA typically suffers from lower sensitivity than the well-established enzyme-linked immunosorbent assay (ELISA), limiting its wide application as an analytical tool that can be run with trace levels of an analyte. Herein, a highly sensitive FPIA for detecting amantadine (AMD) in chicken is described. To achieve high sensitivity, nine chemical tracers of AMD that employ different fluoresceins, fluorescein derivatives, and haptens were synthesized and paired with four previously produced monoclonal antibodies (mAbs). The effect of the tracer structure on the sensitivity of FPIA was investigated and discussed. We found that the tracers with a linear and shorter bridge between adamantane and fluorescein generally provided higher sensitivity. After optimization, N'-(1-adamantyl) ethylenediamine (AEDA), an AMD structural analogue labeled with fluorescein isothiocyanate (FITC), achieved the lowest IC50 value (1.0 ng/ml) in the FPIA, which was comparable to that of the heterologous ELISA format that used the same mAb7G2. We also investigated the possible recognition mechanism of mAbs in terms of conformational and electronic aspects. The developed FPIA was applied to chicken to detect AMD residue, demonstrating a limit of detection (LOD) of 0.9 µg/kg with recoveries of 76.5-89.3% and coefficients of variation (CVs) below 14.5%. These results show that the proposed FPIA is an efficient, accurate, and convenient method for the rapid screening of AMD residues in chicken. PRACTICAL APPLICATION: The fluorescence polarization immunoassay (FPIA) was developed to determine and quantify amantadine (AMD) in chicken samples with high sensitivity. This homogeneous method avoids coating and washing steps and may provide high-throughput AMD screening in chicken in 10 min with high accuracy and precision. FPIA can be used as a monitoring tool and contribute significantly to the rapid detection of AMD in chicken.

Polo-like kinase 4 (PLK4) promotes tumorigenesis and is associated with the prognosis of several solid tumors, while its clinical role in patients with renal cell carcinoma (RCC) remains unidentified. The present study aimed to analyze the association of PLK4 with clinicopathological characteristics and long-term prognosis in patients with RCC. The present study detected PLK4 protein and mRNA expression using immunohistochemical and reverse transcription-quantitative PCR assays in 120 patients with RCC. Disease-free survival (DFS) and overall survival (OS) time were calculated based on a median follow-up duration of 6.9 years (range, 1.2-9.9 years). PLK4 protein expression was elevated in tumor tissues compared with adjacent tissues (P0.001). Upregulation of PLK4 protein was associated with increased T stage (P=0.023), N stage (P=0.014) and TNM stage (P=0.007). Additionally, elevated tumor PLK4 protein expression exhibited an associating trend (without statistical significance) with reduced DFS rate (P=0.066) and was associated with decreased OS rate (P=0.036). However, univariate Cox's regression analysis indicated that high PLK4 protein expression (compared with low PLK4 protein expression) was associated with reduced OS rate (P=0.040) but not with PFS rate (P=0.070). Following adjustment by multivariate Cox's regression analysis, PLK4 protein expression was associated with neither DFS nor OS rate (both P0.050). Additionally, PLK4 mRNA expression was further detected in some patients (for which fresh specimens frozen in liquid nitrogen were available) to validate the aforementioned observations, and the expression was elevated in tumor tissues compared with adjacent tissues. Furthermore, increased PLK4 mRNA expression was associated with tumor size ≥7 cm, high TNM stage and reduced DFS rate (all P0.050). PLK4 possesses a certain clinical utility in monitoring the clinical stage of patients with RCC, while its prognostic value requires further validation.

In this study, deep eutectic solvent (DES), as a new green solvent, was used to extract bioactive alkaloids from Ephedrae Herba using supersonic extraction. In a variety of tested hydrophilic and hydrophobic DESs, DES composed of choline chloride and xylitol was proved to be the most efficient solvent. Factors affecting extraction efficiency, including the mole ratio of hydrogen bond acceptor/hydrogen bond donor, water contention, and solid/liquid ratio, were optimized individually. Under optimal conditions, the yield of ephedrine (EP) and pseudoephedrine obtained using this new method was 14.24 and 4.32 mg/g, respectively, which was higher than that using the traditional solvent (acidified water and methanol). Furthermore, the extraction mechanism of DES and EP was investigated using molecular dynamics simulation study. Structural properties such as radial distribution functions and average number of hydrogen bonds were then computed. The results showed that hydrogen bonds and van der Waals forces are important driving forces of extraction; in addition, the hydrogen bonds between the Cl atom of choline chloride and N atom of EP played a dominant part in the extraction process. Based on the extraction principle, the extraction method using choline chloride as extraction solvent was also discussed.

Lekethromycin (LKMS), a novel macrolide lactone, is still unclear regarding its absorption. Thus, we conducted this study to investigate the characteristics of LKMS in rats. We chose the ultrafiltration method to measure the plasma protein binding rate of LKMS. As a result, LKMS was characterized by quick absorption, delayed elimination, and extensive distribution in rats following intramuscular (im) and subcutaneous (sc) administration. Moreover, LKMS has a high protein binding rate (78–91%) in rats at a concentration range of 10–800 ng/mL. LKMS bioavailability was found to be approximately 84–139% and 52–77% after im and sc administration, respectively; however, LKMS was found to have extremely poor bioavailability after oral administration (po) in rats. The pharmacokinetic parameters cannot be considered linearly correlated with the administered dose. Additionally, LKMS and its corresponding metabolites were shown to be metabolically stable in the liver microsomes of rats, dogs, pigs, and humans. Notably, only one phase I metabolite was identified during in vitro study, suggesting most of drug was not converted. Collectively, LKMS had quick absorption but poor absorption after oral administration, extensive tissue distribution, metabolic stability, and slow elimination in rats.

The dominance effect is a kind of non-additive effect due to the interaction between alleles at the same locus. Quantitative traits such as growth traits in farm animals have been found to be influenced by dominance effects. However, dominance effects are usually ignored in the genome-wide association study (GWAS) of complex traits for farm animals. In this study, we performed GWAS and genetic parameters estimation for the two traits age at 100 kg (AGE) and backfat thickness at 100 kg (BF) of 3572 Large White pigs. The pigs were from three breeding farms of China and were genotyped by an in-house designed 50k SNP chip. Our results showed significant non-zero variance for the dominance effect of AGE, while the dominance effect of BF was not significant. Using a GWAS model accounting for both additive and dominance effects, we identified three additive and two dominance significant SNPs for the trait AGE. For the trait BF, three genome-wide significant additive SNPs were detected, but no significant SNP was found for the dominance effect. In total, six important functional genes (NPAS3, USP16, PARN, ARL15, GPC3, ABHD4) near significant SNPs were identified as candidate genes associated with AGE or BF. Notably, ARL15 and PARN were associated with AGE near the dominance association signals. Overall, the newly detected SNPs and newly identified candidate genes in our study added new information about the genetic architectures of growth and fatness traits in pigs, and have the potential to be applied to the pig breeding program in the future.

Phallotoxins, toxic cyclopeptides found in wild poisonous mushrooms, are predominant causes of fatal food poisoning. For the early and rapid diagnosis mushroom toxin poisoning, a highly sensitive and robust monoclonal antibody (mAb) against phallotoxins was produced for the first time. The half-maximum inhibition concentration (IC50) values of the mAb-based indirect competitive ELISAs for phallacidin (PCD) and phalloidin (PHD) detection were 0.31 ng mL−1 and 0.35 ng mL−1, respectively. In response to the demand for rapid screening of the type of poisoning and accurate determination of the severity of poisoning, colloidal gold nanoparticle (GNP) and time-resolved fluorescent nanosphere (TRFN) based lateral flow assays (LFA) were developed. The GNP-LFA has a visual cut-off value of 3.0 ng mL−1 for phallotoxins in human urine sample. The TRFN-LFA provides a quantitative readout signal with detection limit of 0.1 ng mL−1 in human urine sample. In this study, urine samples without pretreatment were used directly for the LFA strip tests, and both two LFAs were able to accomplish analysis within 10 min. The results demonstrated that LFAs based on the newly produced, highly sensitive, and robust mAb were able to be used for both rapid qualitative screening of the type of poisoning and accurate quantitative determination of the severity of poisoning after accidental ingestion by patients of toxic mushrooms.

To describe the interaction between viral infection and immune response, we establish a mathematical model with intracellular delay and investigate an optimal control problem to examine the effect of antiviral therapy. Dynamic analysis of the proposed model for the stability of equilibria and Hopf bifurcation is conducted. Theoretical results reveal that the dynamical properties are determined by both the immune-inactivated reproduction number and the immune-activated reproduction number. With the aim of minimizing the infected cells and viral load with consideration for the treatment costs, the optimal solution is discussed analytically. Numerical simulations are performed to suggest the optimal therapeutic strategy and compare the model-predicted consequences.

Inflammatory bowel disease (IBD) represents a highly recurrent gastrointestinal disorder and global public health issue. However, it lacks effective and safe strategies for its control. Although Ginkgo biloba extract (GBE) has been suggested to exhibit preventive and therapeutic activity for the control of IBD, whether its activity is associated with its ability to modulate intestinal microbiota remains to be addressed. To investigate the effect of GBE on controlling IBD, a Citrobacter Rodentium (CR)-induced mouse colitis model was used, and then histopathological examinations, biochemical assays, immunohistochemistry, and immunoblotting were performed to detect histological changes, cytokines, and tight junction (TJ) proteins in the intestine samples. We also studied 16s rRNA to detect changes in intestinal microbiota and used GC-MS to determine the microbiota-related metabolites short chain fatty acids (SCFAs). The results of our studies revealed that pre-treatment with GBE was sufficient for protecting the animals from CR-induced colitis. As a mechanism for GBE activity, GBE treatment was able to modulate the intestinal microbiota and increase the SCFAs capable of decreasing the pro-inflammatory factors and up-regulating the anti-inflammatory factors while elevating the intestinal-barrier-associated proteins to maintain the integrity of the intestines. Accordingly, our results led to a strong suggestion that GBE should be seriously considered in the preventive control of CR-induced colitis and in the development of effective and safe therapeutic strategies for controlling IBD.

This study aims to conduct galloping experiments using a full aeroelastic model to investigate the galloping controlling effects of interphase spacers with different kinds of arrangements on three-phase iced eight-bundled transmission lines. A low-speed wind tunnel was designed and built to assess the compact transmission lines on a single span. The similarity conditions between the aeroelastic model and the prototype were determined by the similarity theory and the proposed modification method. Four common arrangements of interphase spacers were considered. Compared with the situation without interphase spacers, the composite amplitude reduction rate of the first two modes and amplitude reduction rate varying with wind speed were evaluated. Then, the anti-galloping effects of interphase spacers were investigated and the controlling effects of interphase spacers on the interphase distance were analyzed. Besides, the corresponding arrangements under different conditions were determined. In addition, the galloping phenomena varying with wind speed were explored. The results suggested that their galloping phenomena were changed because of the effects of interphase spacers, and coupling effects of interphase spacers with different arrangements were different. This research could be used to estimate the positions of interphase spacers and offered a theoretical foundation for the anti-galloping design of transmission lines.

PI3K/Akt/mTOR signaling pathway plays an important role in tumor development. mTOR overexpression and PI3K/ Akt/mTOR signaling pathway enhancement were found in endometrial cancer (EC). MiR-101 was found downregulated in EC. Bioinformatics analysis showed the binding site between miR-101 and the 3'-UTR of mTOR mRNA. This study investigated the role of miR-101 in affecting EC proliferation, apoptosis, and invasion, and mediating mTOR expression. EC tumor tissue and normal endometrial tissue were collected from Jinan maternity and child care hospital. MiR-101 and mTOR expressions were detected. The targeted relationship between miR-101 and mTOR was tested by dual-luciferase reporter gene assay. MiR-101, mTOR, p-mTOR, and p-4EBP1 expressions between HEEC and HEC-1A cells were compared. HEC-1A cells were cultured in vitro and divided into five groups, including miR-NC, miR-101 mimic, si-NC, si-mTOR, and miR-101 + si-mTOR. mTOR, p-mTOR, and p-4EBP1 expressions were compared. Cell apoptosis was evaluated by flow cytometry. Cell malignant proliferation was evaluated by colony formation assay. Cell invasion was determined by Transwell assay. MiR-101 and mTOR expressions significantly declined in EC tissue compared with normal endometrium. MiR-101 showed targeted relationship with mTOR. MiR-101 reduced, while mTOR, p-mTOR, and p-4EBP1 levels elevated in HEC-1 cells compared with HEEC cells. MiR-101 mimic and/or si-mTOR transfection obviously reduced mTOR, p-mTOR, and p-4EBP1 expressions, decreased colony formation, decreased invasion, and enhanced apoptosis in HEC-1A cells. MiR-101 downregulated and mTOR elevated in EC tissue. MiR-101 decreased HEC-1A cell proliferation and invasion, and upregulated apoptosis through targeting mTOR to attenuate PI3K/Akt/ mTOR signaling pathway activity.

In this study, a homologous multi-wavelength fluorescence polarization immunoassays (MWFPIA) for rapid determination of amantadine (AMD) and ribavirin (RVB) simultaneously was established. The MWFPIA could quantify AMD and RVB concentration simultaneously in 1 min. After optimisation, long-wavelength tracers AEDA-AF647 with monoclonal antibody (Mab) 1A12 and RVB-CP-EDF with polyclonal antibody (Pab) G412 were chosen for the development of MWFPIA. The limit of detections (LODs) of AMD and RVB were 1.7 and 1.0 μg/kg in chickens, and 17.6 and 10.4 μg/L in human serum, respectively. Recoveries of AMD and RVB in chickens were 61.2–94.9% and 87.3–90.2%, respectively with coefficient of variations (CVs) lower than 16.7%. For human serum, recoveries were 60.2–84.3% and 63.5–74.2% for AMD and RVB, respectively, and CVs was lower than 15.3%. The results indicated that the MWFPIA could be used for the monitoring of antiviral drugs with short analysis time, great accuracy and high throughput.

To monitor the contamination of a type A trichothecene, diacetoxyscirpenol (DAS), one monoclonal antibody (mAb) 8A9 with high affinity and specificity was prepared in the present study. The mAb 8A9 showed a 50% inhibition concentration (IC50) of 0.31 μg/L, which is of the highest affinity reported to date. An indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) and lateral flow immunoassay (LFIA) based on mAb 8A9 were developed and exhibited limits of detection as low as 0.65 μg/kg and 100 μg/kg in rice samples, respectively. The molecular recognition mechanism of mAb 8A9 to DAS was explored by molecular docking. The results showed that the hydrophobic amino acids of mAb 8A9 interacted with DAS by forming hydrogen bonds and a pi-sigma bond, which lead to a highly specific recognition of DAS. In summary, we produced one mAb, developed ELISA and LFIA for DAS detection in rice with significantly sensitivity, specificity, accuracy, and precision.

The pharmacokinetic behaviours of amoxicillin (AMX) and clavulanic acid (CA) in swine were studied after either an intravenous or oral administration of AMX (10 mg/kg) and CA (2.5 mg/kg). The concentrations of these two medicines in swine plasma were determined using high-performance liquid chromatographic-tandem mass spectrometry, and the data were analysed using a noncompartmental model with the WinNonlin software. After intravenous administration, both substances were absorbed rapidly and reached their effective therapeutic concentration quickly. CA was eliminated more slowly compared with AMX. Moreover, the distribution volume of AMX was larger than that of CA, suggesting that AMX could penetrate tissues better. After oral administration of the granular formulation, no significant difference was observed in the mean elimination half-life value between AMX and CA. The mean maximal plasma concentrations of AMX and CA, reached after 1.14 and 1.32 hr, were 2.58 and 1.91 μg/m, respectively. The mean oral bioavailability of AMX and CA was 23.6% and 26.4%, respectively. After oral administration, the T>MIC50 for three common respiratory pathogens was over 6.12 hr. Therefore, oral administration could be more effective in the clinical therapy of pigs, especially when administered twice daily.

The pharmacokinetic properties of three formulations of vitacoxib were investigated in horses. To describe plasma concentrations and characterize the pharmacokinetics, 6 healthy adult Chinese Mongolian horses were administered a single dose of 0.1 mg/kg bodyweight intravenous (i.v.), oral paste, or oral tablet vitacoxib in a 3-way, randomized, parallel design. Blood samples were collected prior to and at various times up to 72 hr postadministration. Plasma vitacoxib concentrations were quantified using UPLC-MS/MS, and pharmacokinetic parameters were calculated using noncompartmental analysis. No complications resulting from the vitacoxib administration were noted on subsequent administrations, and all procedures were tolerated well by the horses throughout the study. The elimination half-life (T1/2λz ) was 4.24 ± 1.98 hr (i.v.), 8.77 ± 0.91 hr (oral paste), and 8.12 ± 4.24 hr (oral tablet), respectively. Maximum plasma concentration (Cmax ) was 28.61 ± 9.29 ng/ml (oral paste) and 19.64 ± 9.26 ng/ml (oral tablet), respectively. Area under the concentration-versus-time curve (AUClast ) was 336 ± 229 ng hr/ml (i.v.), 221 ± 94 ng hr/ml (oral paste), and 203 ± 139 ng hr/ml, respectively. The results showed statistically significant differences between the 2 oral vitacoxib groups in Tmax value. T1/2λz (hr), AUClast (ng hr/ml), and MRT (hr) were significantly different between i.v. and oral groups. The longer half-life observed following oral administration was consistent with the flip-flop phenomenon.

The pharmacokinetics of carbetocin, which is used to control postpartum hemorrhage after giving birth, was studied in cows and gilts after a single intravenous (IV) or intramuscular (IM) injection. Blood samples from animals were assessed by oxytocin radioimmunoassay, and then the pharmacokinetic parameters were calculated using a noncompartmental model. For gilts, there was no significant difference between half-life (T1/2λZ ), mean residue time (MRT), and maximum concentration (Cmax ) between IM and IV administration. Conversely, the time to reach the Cmax (Tmax ) and MRT were higher following administration of 350 μg/animal in cows via the IM administration compared with IV. The longest T1/2λZ was 0.85 hr, indicating carbetocin was absorbed and eliminated rapidly in both animal species after administration. The Tmax was similar between cows and gilts following IM administration. Moreover, the Cmax after IM injection was about half that of IV administration in both animals. The bioavailability was more than 80% in cows, suggesting administration via the IM route is efficient. This is in agreement with the longer T1/2λZ in cows after IM administration. However, the IV route is recommended for gilts due to a lower bioavailability (35%) and shorter T1/2λZ after IM administration compared with IV.

In this study, a fluorescence polarization immunoassay (FPIA) was developed based on the single-chain variable fragments (scFvs) for fumonisin Bs (FBs). The scFvs were prepared from FBs-specific monoclonal antibody secreting hybridomas (4F5 and 4B9). The established FPIA could determine the sum of fumonisin B1 (FB1) and fumonisin B2 (FB2) within a short time. The IC50 of FPIA for the detection of FB1 and FB2 were 29.36 ng/ml and 1,477.82 ng/ml with 4F5 scFv, and 125.16 ng/ml and 30.44 ng/ml with 4B9 scFv, so the 4B9 scFv was selected for detection of FB1 and FB2 in maize samples with a limit of detection of 441.54 μg/kg and 344.933 μg/kg. The recoveries ranged from 84.7 to 104.1% with a coefficient of variation less than 14.1% in spiked samples, and the result of the FPIA method was in good consistency with that of HPLC-MS/MS. To supply a better understanding of the immunoassay results, the interactions mechanism of scFvs-FBs was further revealed by the homology modelling, molecular docking, and molecular dynamic simulation. It was indicated that six complementarity-determining regions (CDRs) were involved in 4B9 scFv recognition, forming a narrow binding cavity, and FB1/FB2 could be inserted into this binding cavity stably through strong hydrogen bonds and other interactions. While in 4F5 scFv, only the FB1 stably inserted in the binding pocket formed by four CDRs through strong hydrogen bonds, and FB2 did not fit the binding cavity due to the lack of hydroxyl at C10, which is the key recognition site of 4F5 scFv. Also, the binding energy of FB2-4B9 scFv complex is higher than the FB2-4F5 scFv complex. This study established a FPIA method with scFv for the detection of FB1 and FB1 in maize, and systematically predicted recognition mechanism of FBs and scFvs, which provided a reference for the better understanding of the immunoassay mechanism.

In this paper, we derive a delayed epidemic model to describe the characterization of cytotoxic T lymphocyte (CTL)-mediated immune response against virus infection. The stability of equilibria and the existence of Hopf bifurcation are analysed. Theoretical results reveal that if the basic reproductive number is greater than 1, the positive equilibrium may lose its stability and the bifurcated periodic solution occurs when time delay is taken as the bifurcation parameter. Furthermore, we investigate an optimal control problem according to the delayed model based on the available therapy for hepatitis B infection. With the aim of minimizing the infected cells and viral load with consideration for the treatment costs, the optimal solution is discussed analytically. For the case when periodic solution occurs, numerical simulations are performed to suggest the optimal therapeutic strategy and compare the model-predicted consequences.

In this study, the stability parameter range of a tethered quadrotor unmanned aerial vehicle (UAV) under the action of the transient wind field is numerically analyzed, which can provide a theoretical basis for the design and application of such systems. Three factors affecting the stability of tethered UAV system are determined, namely, cable tension, cable elongation, and UAV vibration velocity, and the corresponding judgment criteria are obtained. Specifically, the priority of the three criteria sequentially decreases. According to these criteria, the stability parameter range of the tethered UAV is examined under the cable parameters such as length, diameter, and elastic modulus and the environmental parameters such as the amplitude and period of the wind field. The results show that for designing the tethered UAV structure, by reducing the length of the tethered cable and increasing its diameter and elastic modulus, the working stability of tethered UAV system can be improved.

PDP1 has been reported in multiple diseases. However, it has not been fully explored in ovarian cancer (OC). The public data was downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differentially expressed gene analysis was conducted out using the limma package. Prognosis analysis was performed using the survival package. Gene Set Enrichment Analysis (GSEA) was performed using the fgsea package. Immune infiltration analysis was performed based on the CIBERSORT algorithm. CCK8 assay was used to evaluate the cell proliferation ability of cancer cells. Transwell assay was used for the invasion and migration ability. Our result showed that PDP1 was overexpressed in OC tissue in RNA and protein level based on multiple databases (TCGA, GSE18520, GSE27651, and GSE54388). At the same time, we found PDP1 was correlated with poor prognosis and worse clinical parameters. In vitro experiment showed that PDP1 could significantly promote proliferation, invasion, and migration ability of OC cells. GSEA analysis showed that in the OC patients with high PDP1 expression, the pathway of IL6/JAK/STAT3 signaling, interferon-alpha response, apoptosis, adipogenesis, KRAS signaling, and IL2/STAT5 signaling was activated, which might be responsible for its oncogenic effect in OC. Immune infiltration analysis indicated that PDP1 was positively correlated with activated myeloid dendritic cells, resting CD4 memory T cells, neutrophil, and M1 and M2 macrophages, yet negatively correlated with M0 macrophages, plasma B cells, γδT cells, and activated CD4 memory T cells. Drug sensitivity analysis showed a negative correlation between PDP1 expression and the IC50 of bleomycin and gemcitabine, yet a positive correlation of cisplatin, indicating that the OC patients with high PDP1 expression might be more sensitive to bleomycin and gemcitabine and more resistant to cisplatin. PDP1 could facilitate OC progression and is associated with patient prognosis and chemosensitivity, making it an underlying biomarker of OC.

Deep eutectic solvents (DESs) were applied as eco-friendly solvents in this study for the extraction of alkaloids from lotus leaf, including O-nornuciferine, N-nornuciferine, nuciferine and roemerine. A series of hydrophilic and hydrophobic DESs with different hydrogen bond donors and a acceptors were synthesized and screened for a suitable DESs for extraction of alkaloids from lotus leaf. The study results showed that the hydrophilic DES with choline chloride and propanediol had the highest extraction yield. The main factors affecting the extraction efficiency-choline chloride-propanediol ratio, water content in deep eutectic solvents, solid-liquid ratio and extraction time-were investigated via a single-factor experiment. The optimized extraction conditions were 30% of water in choline chloride-propanediol (1:4) for heated extraction for 30 min and solid-liquid ratio 1:100 g/ml. Under optimum conditions, the extraction yields of O-nornuciferine, N-nornuciferine, nuciferine and roemerine were 0.069, 0.152, 0.334 and 0.041 g/100 g respectively, which were higher than those of methanol in acidified aqueous solution. This study suggests considerable potential for DESs as promising materials for the green and efficient extraction solvents for bioactive alkaloids from natural sources.

In this study, a fluorescence polarization immunoassay (FPIA) was developed based on the single-chain variable fragments (scFvs) for fumonisin B

Albendazole (ABZ) is one of the benzimidazole anthelmintics, and the overuse of ABZ in breeding industry can lead to drug resistance and a variety of toxic effects in humans. Since the residue markers of ABZ are the sum of ABZ and three metabolites (collectively referred to as ABZs), albendazole-sulfone (ABZSO2), albendazole-sulfoxide (ABZSO), and albendazole-2-amino-sulfone (ABZNH2SO2), an antibody able to simultaneously recognize ABZs with high affinity is in urgent need to develop immunoassay for screening purpose. In this work, an unreported hapten, 5-(propylthio)-1H-benzo[d]imidazol-2-amine, was designed and synthesized, which maximally exposed the characteristic sulfanyl group of ABZ to the animal immune system to induce expected antibody. One monoclonal antibody (Mab) that can simultaneously detect ABZs was obtained with IC50 values of 0.20, 0.26, 0.77, and 10.5 μg/L for ABZ, ABZSO2, ABZSO, and ABZNH2SO2 in ic-ELISA under optimized conditions respectively, which has been never achieved in previous reports. For insight into the recognition profiles of the Mab, we used computational chemistry method to parameterize cross-reactive molecules in aspects of conformation, electrostatic fields, and hydrophobicity, revealing that the hydrophobicity and conformation of characteristic group of molecules might be the key factors that together influence antibody recognition with analytes. Furthermore, the practicability of the developed ic-ELISA was verified by detecting ABZs in spiked milk, beef, and liver samples with recoveries of 60% to 108.8% and coefficient of variation (CV) of 1.0% to 15.9%.

To investigate the vibration behavior of ship-borne tethered UAVs under taut–slack conditions, the Hamilton principle is used to establish the three-dimensional dynamic equations of the ship-borne tethered UAVs while taking into account geometric nonlinearity and simplifying them into the corresponding stress wave equations. By employing the characteristic line technique to solve the stress wave equation of ship-borne tethered UAVs, it is possible to numerically determine the effects of various factors on the vibration behavior of these drones. Dimensional analysis is then used to build the experimental model, ensuring that the numerical outcomes are accurate. The findings show that the impact of equilibrium curvature connects longitudinal and transverse waves and that the geometric dispersion of stress wave propagation in the tethered cable is caused by equilibrium curvature. The standing wave takes the lead and causes subharmonic and frequency doubling components in the top tension response when the end excitation frequency is near the tethered UAVs’ natural frequency. Additionally, the cable’s center as well as its end will display the highest dynamic tension value.

We formulate a mathematical model for vector-borne disease with impulsive perturbation based on indoor residual spraying. The dynamical properties are studied theoretically and numerically. It is shown that with consideration of impulsive spraying at fixed times, there exists a disease-free periodic solution that is locally stable when the threshold $${\mathcal {R}}_0$$ is less than unity, otherwise the disease is uniformly persistent if $${\mathcal {R}}_0>1$$. Furthermore, the bifurcation analysis is performed, revealing the possible existence of nontrivial periodic solution bifurcated from the disease-free periodic solution at $${\mathcal {R}}_0=1$$. In addition to simulations of parameter sensitivity, when implementing impulsive spraying once the number of infected humans exceeds a threshold level, the effectiveness of such state-dependent control is also conducted numerically.

Altrenogest, a synthetic progestogen, is characterized by its estrus synchronization in mares, ewes, sows, and gilts. To investigate the pharmacokinetic profile and evaluate its accumulation in gilts, 18 oral doses of 20 mg altrenogest/gilt/day were given to eight healthy gilts at an interval of 24 hr. Plasma samples were collected, and altrenogest was determined by ultra-high-performance liquid chromatography with mass spectrometry. WinNonlin 6.4 software was used to calculate the pharmacokinetic parameters through noncompartmental model analysis. After the first administration (D 1), the pharmacokinetic parameters, including Tmax , Cmax , and the elimination half-life (T1/2λz ), were similar to those observed after the final administration (D 18). However, the mean residence time at D 1 was significantly lower than D 18. As a whole, the mean steady-state plasma concentration (Css ), degree fluctuation (DF), accumulation factor (Rac ), and area under the plasma concentration-time curve in steady state (AUCss ) were 22.69 ± 6.15 ng/ml, 270.64 ± 42.51%, 1.53 ± 0.23, and 544.63 ± 147.49 ng hr/ml, respectively. These results showed that after 18 consecutive days of oral administration of altrenogest, plasma concentrations of altrenogest had a certain degree of fluctuation, without significant accumulations.

Fluorescence polarization (FP) assays play an important role in the detection of chemical contaminants in food and environmental due to a number of key advantages since last century. In recent decades, FP assays have achieved great progress thanks to developments in materials science and labelling techniques. This comprehensive review provides the state of art in methods design, recognition elements, fluorophores, multi-targeted analysis, practical applications with real samples, and the challenges of deploying FP assays for the detection of chemical contaminants. These new information and insightful commentary of the review will be critically important to the development and innovation of next-generation FP assays.

Three experiments were conducted to determine the digestible (DE) and metabolizable energy (ME) values, and apparent (AID) and standardized ileal digestibility (SID) of amino acids (AAs) in degossypolized cottonseed protein (DCP), and to evaluate the effects of DCP as a replacement for soy protein concentrate (SPC) or fish meal (FM) on growth performance and diarrhea frequency of nursery pigs. In Exp. 1, 12 barrows (38.5 ± 3.0 kg initial BW) were allotted into 2 dietary treatments to determine the DE and ME values of DCP. In Exp. 2, 12 barrows (31.5 ± 2.2 kg initial BW) fitted with ileal T-cannula were allotted into 2 dietary treatments to determine the AID and SID of AAs in DCP using the exogenous indicator method. In Exp. 3, 144 nursery pigs (7.4 ± 1.1 kg initial BW) were randomly assigned to 1 of 4 treatments, including a control diet with 10% SPC and 4% FM, and 3 experimental diets formulated by replacing SPC with 5% or 10% DCP or replacing FM with 4% DCP, respectively. The results showed that the concentrations of crude protein (CP) and most AAs in DCP were close to those in SPC, but the fiber levels in DCP was greater than that in SPC. The DE and ME values of DCP were 19.11 and 17.77 MJ/kg on dry matter (DM) basis, respectively, and the AID and SID of indispensable AAs were ranged from 0.73 to 0.93 and 0.76 to 0.94, respectively. There were no differences in growth performance, diarrhea frequency and ATTD of gross energy (GE), DM and CP among the 4 treatments during day 0–28 fed to nursery pigs. However, pigs fed diets with 10% DCP had lower (P

A multiplex immunochromatographic assay (ICA) based on dual-color fluorescent microspheres (FMs) as a sensitive label was developed for the first time. Two typical algae toxins, microcystin-LR (MC-LR) and okadaic acid (OA), were chosen as proof-of concept targets to evaluate the feasibility of this ICA format. Commercial red- and green-colored FMs were selected to couple with monoclonal antibodies as fluorescent probes. The use of dual-wavelength FMs as labels guaranteed a lower consumption of material strips, lower sample volume, and shorter reaction time without increasing the length of ICA strips. Under optimal conditions, the multiplex FM-ICA could be completed in 20 min and reached limits of detection for the simultaneous determination of MC-LR and OA in fish samples, which were 0.074 and 2.42 μg/kg, respectively. The developed technique was validated using artificially spiked and naturally contaminated fish samples. Ultra-high-performance liquid chromatography-tandem mass spectrometry was used as confirmatory technique. In summary, this portable ICAs detection mode based on dual-wavelength FMs provided a reliable and sensitive on-site detection of multiple contaminants in food samples, which opens a new field for application of FMs in food safety.

Antibody-based sensors are the most widely used for screening antibiotic residues in food samples. However, these sensors always suffer from cross-reacting antibiotics which are able to bind the employed antibodies in a manner similar to the target, thus resulting in inaccurate quantification. In this study, we developed a highly specific and sensitive chemiluminescence aptasensor for sulfamethazine (SMZ) by employing the supernormal selectivity of a new selected aptamer. Four SMZ-specific aptamers (Kd ranging from 79 to 274 nM) were selected in vitro by MB-SELEX with an intentional counter selection to avoid the recognition other sulfonamides, which is impossible to achieve in the corresponding procedure of antibody production. The binding mechanism of aptamers for SMZ was further analyzed and clarified with molecular simulation and docking. Under optimum conditions, the chemiluminescence aptasensor based on the highest affinity aptamer named SA07 provided a limit of detection of 0.92 ng/mL with negligible cross-reactivity with the 27 tested sulfonamides. The developed aptasensor was applied to milk samples, and achieved good accuracy and precision. These results demonstrated that the integration of an aptamer and chemiluminescence in a sensor platform is a promising method for the sensitive, specific, rapid and accurate detection of antibiotic residues of interest in food samples.

The objectives of this study were to evaluate the prediction performance of the single-step genomic BLUP method using a multi-trait random regression model in genomic evaluation for milk production traits of Chinese Holsteins, and investigate how parameters w, τ, and ω used in the construction of the combined relationship matrix (H) affected prediction accuracy and bias. A total of 2.8 million test-day records from 0.2 million cows were available for milk, protein, and fat yields. Pedigree information included 0.3 million animals and 7,577 of them were genotyped with medium-density single nucleotide polymorphism marker panels. Genotypes were imputed into Geneseek Genomic Profiler HD (GeneSeek, Lincoln, NE) including 77K markers. A reduced data set for evaluating models was extracted from the full data set by removing test-day records from the last 4 yr. Bull and cow validation populations were constructed for each trait. We evaluated the prediction performance of the multiple-trait multiple-lactation random regression single-step genomic BLUP (RR-ssGBLUP) models with different values of parameters w, τ, and ω in the H matrix, taking consideration of inbreeding. We compared RR-ssGBLUP with the multiple-trait multiple-lactation random regression model based on pedigree and genomic BLUP. De-regressed proofs for 305-d milk, protein, and fat yields averaged over 3 lactations, which were calculated from the full data set, were used for posteriori validations. The results showed that RR-ssGBLUP was feasible for implementation in breeding practice, and its prediction performance was superior to the other 2 methods in the comparison, including prediction accuracy and unbiasedness. For bulls, RR-ssGBLUP models with w0.05τ2.0ω1.0,w0.05τ2.5ω1.0, and w0.1τ1.6ω0.4 achieved the best performance for milk, protein, and fat yields, respectively. For cows, the RR-ssGBLUP with w0.2τ1.6ω0.4 performed the best for all 3 traits. The H matrix constructed with larger τ and smaller ω gave better convergence in solving mixed model equations. Among different RR-ssGBLUP models, the differences in validation accuracy were small. However, the regression coefficient indicating prediction bias varied substantially. The increase of w and τ, and decrease of ω, led to an increase in the regression coefficient. The results demonstrated RR-ssGBLUP is a good alternative to the multi-step approach, but the optimal choice of parameters should be found via preliminary validation study to achieve the best performance.

The aminoglycoside antibiotic neomycin, which is used to treat external or internal bacterial infections, is primarily administered in veterinary medicine as a sulfate salt. However, no information is available on the pharmacokinetic characteristics and absolute availability of neomycin sulfate after intravenous (i.v.) and oral (p.o.) administrations in swine. Here, these parameters were studied in swine after i.v. and p.o. doses of single 15 mg/kg body weight doses. The blood samples were assessed using ultra-high-performance liquid chromatography-tandem mass/mass spectrometry (UPLC-MS/MS) and pharmacokinetic parameters were analyzed using a non-compartmental model. In swine, after the p.o. administration, the elimination half-life, mean residue time from t0 to the last collection point, mean maximum concentration, mean time to reach maximum concentration and area under concentration-time curve from t0 to the last collection point values were 12.43 ± 7.63 h, 10.25 ± 4.32 h, 0.11 ± 0.07 μg/ml, 1.92 ± 0.97 h and 1.23 ± 0.78 μg·h/ml, respectively, whereas after the i.v. administration, the values were 5.87 ± 1.12 h, 6.07 ± 0.49 h, 15.80 ± 1.32 μg/ml, 0.30 ± 0.38 h and 76.14 ± 3.52 μg·h/ml, respectively. The absolute bioavailability of neomycin sulfate B was 4.84%±0.03.

Ribavirin (RBV) is an effective antiviral drug, whose use is prohibited in animal husbandry worldwide. In this work, a novel immunizing hapten of RBV, named Hapten 4, was designed by comparing the conformational and electronic properties of RBV and haptens based on computational chemistry. Hapten 4 was synthesized and conjugated with carrier proteins to produce monoclonal antibody (mAb). The obtained mAb 4C3 for RBV exhibited an IC50 value of 6.24 ng/ml in an indirect competitive enzyme-linked immunosorbent assay (icELISA) and displayed no cross-reaction with five other antiviral drugs, including amantadine. The applicability of the developed icELISA was verified in chicken, with a calculated limit of detection of 4.23 µg/kg. The recoveries in spiked chicken were 79.2%-107.3% with a coefficient of variation less than 15.9%. The results indicated that the produced antibody from the new hapten was reliable and would be useful for RBV screening in chicken. PRACTICAL APPLICATION: RBV is a broad-spectrum antiviral drug, which is commonly used illegally in poultry farms. A high-affinity mAb 4C3 against RBV was produced and used to develop icELISA with acceptable sensitivity and accuracy. The constructed icELISA has excellent performance for detecting RBV residues in chicken.

Lekethromycin, a new macrolide lactone, exhibits significant antibacterial activity. In this study, a reliable analytical ultrahigh-performance liquid chromatography electrospray ionization quadrupole Orbitrap high-resolution mass spectrometry (UPLC-ESI-Orbitrap-MS) method was established and validated for the detection of lekethromycin in rat plasma. After a simple acetonitrile (ACN)-mediated plasma protein precipitation, chromatographic separation was performed on a Phenomenex Luna Omega PS C18 column (30 &times, 2.1 mm i.d. particle size = 3 &mu, m) conducted in a gradient elution procedure using 0.5% formic acid (FA) in ACN and 0.5% FA in water as the mobile phase pumped at a flow rate of 0.3 mL/min. Detection was carried out under positive electrospray ionization (ESI+) conditions in parallel reaction monitoring (PRM) mode with observation of m/z 804.5580 &gt, 577.4056 for lekethromycin and 777.5471 &gt, 619.4522 for gamithromycin (internal standard, IS). The linear range was 5&ndash, 1000 ng/mL (r2 &gt, 0.99), and the lower limit of quantification (LLOQ) was 5 ng/mL. The intra- and inter-day precision (expressed as relative standard deviation, RSD) values were &le, 7.3% and &le, 6.3%, respectively, and the accuracy was &ge, 90% &plusmn, 5.3%. The mean extraction recovery RSD valWeue was &lt, 5.1%. Matrix effects and dilution integrity RSD values were &lt, 5.6% and &lt, 3.2%, respectively. Lekethromycin was deemed stable under certain storage conditions. This fully validated method was effectively applied to study the pharmacokinetics of lekethromycin after a single intravenous administration of 5 mg/kg in rats. The main pharmacokinetic parameters were T1/2&lambda, z, CL_obs and VZ_obs were 32.33 &plusmn, 14.63 h, 0.58 &plusmn, 0.17 L/h/kg and 25.56 &plusmn, 7.93 L/kg, respectively.

Emerging molecular diagnostic methods are more sensitive and objective, which can overcome the intrinsic failings of morphological diagnosis. Here, a RT-PCR-based in vitro diagnostic test kit (LungMe®) was developed and characterized to simultaneously quantify the DNA methylation of SHOX2 and RASSF1A in FFPE tissue specimens. The clinical manifestations were evaluated in 251 FFPE samples with specificity and sensitivity of 90.4 and 89.8%, respectively. Furthermore, the quantitative analysis shows that the degree of SHOX2 methylation was correlated with the stages of lung cancer, but not in the case of RASSF1A. Our observation indicated that the DNA methylation of SHOX2 and RASSF1A may play different roles in cancer development. Comparison of the methylation levels of SHOX2 and RASSF1A between cancer and cancer-adjacent specimens (n = 30), showed they have “epigenetic field defect”. As additional clinical validation, the hypermethylation of SHOX2 and RASSF1A was detected not only in surgical operative specimens, but also in histopathological negative puncture biopsies. SHOX2 and RASSF1A methylation detection can be used to increase sensitivity and NPV, which provide us with a more accurate method of differential diagnosis and are likely to be rapidly applied in clinical examinations.

In this paper, an alcoholism model of SEAR type with different susceptibilities due to public health education is investigated, with the form of continuous differential equations as well as discrete differential equations by applying the Mickens nonstandard finite difference (NSFD) scheme to the continuous equations. Threshold dynamics of the continuous model are performed by constructing Lyapunov functions. The analysis of a discrete model indicates that the alcohol-free equilibrium is globally asymptotically stable if the basic reproductive number R0<1, and conversely, the alcohol-present equilibrium is globally asymptotically stable if R0>1, revealing the consistency and efficiency of the discrete model to preserve the dynamical properties of the corresponding continuous model. In addition, stability preserving and the impact of the parameters related with public health education are conducted by numerical simulations.

The pharmacokinetic parameters of moxidectin (MXD) after intravenous and pour-on (topical) administration were studied in sixteen pigs at a single dose of 1.25 and 2.5 mg/kg BW (body weight), respectively. Blood samples were collected at pretreatment time (0 hr) over 40 days. The plasma kinetics were analyzed by WinNonlin 6.3 software through a noncompartmental model. For intravenous administration (n = 8), the elimination half-life (λZ ), the apparent volume of distribution (Vz ), and clearance (Cl) were 10.29 ± 1.90 days, 89.575 ± 29.856 L/kg, and 5.699 ± 2.374 L/kg, respectively. For pour-on administration (n = 8), the maximum plasma drug concentration (Cmax ), time to maximum plasma concentration (Tmax ), and λZ were 7.49 ng/ml, 1.72, and 6.20 days, respectively. MXD had a considerably low absolute pour-on bioavailability of 9.2%, but the mean residence time (MRT) for pour-on administration 10.88 ± 1.75 days was longer than 8.99 ± 2.48 days for intravenous administration. These results showed that MXD was absorbed via skin rapidly and eliminated slowly. The obtained data might contribute to refine the dosage regime for topical MXD administration.

We formulate a multi-stage SEIR model for infectious diseases with continuous age structure for each successive infectious stage during a long infective period. The model can describe disease progression through multiple infectious stages as in the case of HIV, hepatitis B and hepatitis C. Mathematical analysis shows that the global dynamics are completely determined by the basic reproductive number R 0 . If R 0 ≤ 1 , the disease-free equilibrium is globally asymptotically stable and the disease dies out. If R 0 > 1 , a unique endemic equilibrium is globally asymptotically stable, and the disease persists at the endemic equilibrium. The proof of global stability of endemic equilibria utilizes a Lyapunov functional. Numerical simulations are illustrated and model generalization is also discussed.

To study the anti-galloping effect of interphase spacers with different kinds of arrangements on an iced transmission line, wind tunnel experiments using a full aeroelastic model are carried out in this work. Using similarity theory, the similarity criteria between the aeroelastic model and the prototype have been deduced. A triangular arrangement of three phases is considered, and the arrangements of iced eight-bundled conductors with and without the spacers are divided into six cases. In the experiments, laser sensors at different positions along the span of each phase are used to measure the variation of dynamic displacements with wind speed. Furthermore, galloping characteristics, such as the responses, frequencies, vibration modes, amplitudes and distance between two phases, are obtained for different wind speeds and arrangements. The obtained results show that interphase spacers have a certain inhibitory effect on the first symmetric mode and the first anti-symmetric mode galloping, but not all of the arrangements have a positive effect. The regularity of the variation with wind speed of the anti-galloping effect with interphase spacers is summarized. The galloping amplitude curves indicate that the amplitude is likely to be larger when a modal transformation occurs, in contrast to the results obtained without interphase spacers. The motion of the phase C located close to the diffusion section is different from those of the other two phases. Moreover, due to interphase spacers, the distance between the two phases is increased. The obtained conclusions can be used to predict the positions of interphase spacers and provide a fundamental tool for anti-galloping of eight-bundled conductors.

The mooring cable system in plane motion can be modeled as two coupled partial differential equations, which can be numerical solved by finite difference method directly. The difference scheme is analyzed, and parameters selection for time-marching of displacement and velocity are deduced. The stability condition of the scheme is analyzed through Fourier series method, and parameters range which match stable scheme is given. Then, the parameters range is verified by a numerical example.

A dynamic model of a galloping transmission line able to describe for the coupling of its longitudinal, in-plane, out-of-plane and torsional vibrations is established. It also considers the effects of geometrical nonlinearity and aerodynamic nonlinearity. By the static configuration, the reduced model is obtained. Then, the equations of motion are obtained through the Galerkin method. It contains two in-plane, two out-of-plane and two torsional components. By numerical calculation, the maximum amplitudes at wind speeds are drawn and the galloping behavior of transmission line with thin ice accretions is analyzed. The obtained results show that the second galloping mode is more triggered. The double-mode galloping occurs in all motions, in which the maximum amplitude is bigger than in single-mode galloping. And the double-mode galloping presents the track of inclined ‘8’ in longitudinal direction.

In this study, we formulate a model for hepatitis B virus with control strategies of newborn vaccination and treatment. Mathematical analysis is done theoretically and numerically. The results indicate that the stability of equilibria and persistence of the disease are determined by the basic reproductive number R0. Using the least squares method, the model is applied to simulate yearly new infected cases of hepatitis B in China from 2004 to 2016. Moreover, optimal control problem with newborn vaccination and treatment appearing as functions of time is analyzed by classical optimal theory. The existence of the solution to optimality system is proved, and the simulations are conducted to show the results when optimal control or current intervention is used.

The pharmacokinetic properties of vitacoxib have not been established completely; current dosage recommendations are based on clinical experiences. The primary objective of this study was to describe plasma concentrations and characterize the pharmacokinetics of vitacoxib formulation following oral administrations in horses. Also, the effect of the state of stomach contents on the absorption of vitacoxib was investigated in fed/fasted horses. Blood samples were collected prior to and at various times up to 72 hr post-administration. Drug concentrations were measured using ultra high-performance liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were calculated using Non-Compartmental Analysis Model 200 in WinNonlin™ software. No complications resulting from the vitacoxib administration were noted. All procedures were tolerated well by the horses throughout the study. Cmax was 17.5 ± 9.36 ng/ml (fasted) and 9.47 ± 3.53 ng/ml (fed) following oral administrations. AUClast was 173.7 ± 137.9 ng hr/ml (fasted) and 113.2 ± 70.8 ng h/ml (fed). No significant differences in pharmacokinetic parameters were noted and the results from the pharmacokinetic analysis were similar between the studies, regardless of precision of dosage and fasted and fed conditions. The study extends previous studies describing the pharmacokinetics of vitacoxib following p.o. administration to the horses. Further studies investigating the pharmacokinetics/pharmacodynamics of vitacoxib are necessary to establish adequate therapeutic protocols (optimal dosage and frequency of administration) in horses.

Vitacoxib is a new drug candidate for treatment of inflammation, pain and fever as selective cyclooxygenase-2 inhibitors. In the current study, the mice sperm abnormality, mammalian erythrocyte micronucleus and in vivo chromosome aberration, and teratogenicity in SD rats were evaluated. Vitacoxib did not cause an increase in the frequency of structural chromosome aberrations, nor did it produce an increase in the number of micro nucleated polychromatic erythrocytes at dose of 1250–5000 mg/kg body weight (BW). There were no toxicological signs observed in teratogenicity test in female SD rats at dose of 200–5000 mg/kg BW. Based on these results of these studies, vitacoxib does not appear to be observed mutagenicity and teratogenicity. Keywords: Coxib, Vitacoxib, Mutagenicity, Teratogenicity, Safety evaluation, Toxicity studies