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Porcine epidemic diarrhea virus (PEDV) is responsible for causing fatal watery diarrhea in piglets, resulting in significant economic losses within the pig farming industry. Although vaccination is currently employed as a preventive measure, certain vaccines do not provide complete protection against PEDV field strains. Probiotics present a promising alternative due to their ability to regulate intestinal flora, enhance host immunity, and improve resistance against pathogenic microorganisms. We isolated six lactic acid bacteria (LAB) from the fecal microorganisms of Bama pigs, compared to Limosilactobacillus mucosae DSM13345 of the same genus in which Limosilactobacillus mucosae G01 (L. mucosae G01) proved to have a potent anti-PEDV effect. In a comprehensive manner, L. mucosae G01 significantly augmented the phosphorylation of IRF3 in IPEC-J2 cells, resulting in the induction of interferons (IFN α, IFN ß, IFN λ1, and IFN λ3) and subsequent upregulation of interferon-stimulated genes (ISGs) (MX1, MX2, OAS1, and ZAP) in a dose-dependent fashion, consequently leading to the mitigation of PEDV replication. These findings underscore the promising prospects of L. mucosae G01 as a naturally derived substitute for combating PEDV and other enteric coronavirus infections.
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Although vaccination with inactivated vaccines is a popular preventive method against pseudorabies virus (PRV) infection, inactivated vaccines have poor protection efficiency because of their weak immunogenicity. The development of an effective adjuvant is urgently needed to improve the efficacy of inactivated PRV vaccines. In this study, a promising nanocomposite adjuvant named as MIL@A-SW01-C was developed by combining polyacrylic acid-coated metal-organic framework MIL-53(Al) (MIL@A) and squalene (oil)-in-water emulsion (SW01) and then mixing it with a carbomer solution. One part of the MIL@A was loaded onto the oil/water interface of SW01 emulsion via hydrophobic interaction and coordination, while another part was dispersed in the continuous water phase using carbomer. MIL@A-SW01-C showed good biocompatibility, high PRV (antigen)-loading capability, and sustained antigen release. Furthermore, the MIL@A-SW01-C adjuvanted PRV vaccine induced high specific serum antibody titers, increased splenocyte proliferation and cytokine secretion, and a more balanced Th1/Th2 immune response compared with commercial adjuvants, such as alum and biphasic 201. In the mouse challenge experiment, two- and one-shot vaccinations resulted in survival rates of 73.3 % and 86.7 %, respectively. After one-shot vaccination, the host animal pigs were also challenged with wild PRV. A protection rate of 100 % was achieved, which was much higher than that observed with commercial adjuvants. This study not only establishes the superiority of MIL@A-SW01-C composite nanoadjuvant for inactivated PRV vaccine in mice and pigs but also presents an effective method for developing promising nanoadjuvants. STATEMENT OF SIGNIFICANCE: We have developed a nanocomposite of MIL-53(Al) and oil-in-water emulsion (MIL@A-SW01-C) as a promising adjuvant for the inactivated PRV vaccines. MIL@A-SW01-C has good biocompatibility, high PRV (antigen) loading capability, and prolonged antigen release. The developed nanoadjuvant induced much higher specific IgG antibody titers, increased splenocyte proliferation and cytokine secretion, and a more balanced Th1/Th2 immune response than commercial adjuvants alum and biphasic 201. In mouse challenge experiments, survival rates of 73.3 % and 86.7 % were achieved from two-shot and one-shot vaccinations, respectively. At the same time, a protection rate of 100 % was achieved with the host animal pigs challenged with wild PRV.
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Adyuvantes Inmunológicos , Emulsiones , Animales , Adyuvantes Inmunológicos/farmacología , Emulsiones/química , Ratones , Porcinos , Herpesvirus Suido 1/inmunología , Vacunas contra la Seudorrabia/inmunología , Ratones Endogámicos BALB C , Aceites/química , Femenino , Agua/química , Vacunas de Productos Inactivados/inmunología , Seudorrabia/prevención & control , Seudorrabia/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Citocinas/metabolismoRESUMEN
Adverse perinatal factors can interfere with the normal development of the brain, potentially resulting in long-term effects on the comprehensive development of children. Presently, the understanding of cognitive and neurodevelopmental processes under conditions of adverse perinatal factors is substantially limited. There is a critical need for an open resource that integrates various perinatal factors with the development of the brain and mental health to facilitate a deeper understanding of these developmental trajectories. In this Data Descriptor, we introduce a multicenter database containing information on perinatal factors that can potentially influence children's brain-mind development, namely, periCBD, that combines neuroimaging and behavioural phenotypes with perinatal factors at county/region/central district hospitals. PeriCBD was designed to establish a platform for the investigation of individual differences in brain-mind development associated with perinatal factors among children aged 3-10 years. Ultimately, our goal is to help understand how different adverse perinatal factors specifically impact cognitive development and neurodevelopment. Herein, we provide a systematic overview of the data acquisition/cleaning/quality control/sharing, processes of periCBD.
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Encéfalo , Desarrollo Infantil , Niño , Preescolar , Humanos , Encéfalo/crecimiento & desarrollo , Encéfalo/diagnóstico por imagen , China , Cognición , Bases de Datos Factuales , NeuroimagenRESUMEN
The Porcine epidemic diarrhea virus (PEDV) presents a substantial risk to the domestic pig industry, resulting in extensive and fatal viral diarrhea among piglets. Recognizing the mucosal stimulation triggered by PEDV and harnessing the regulatory impact of lactobacilli on intestinal function, we have developed a lactobacillus-based vaccine that is carefully designed to elicit a strong mucosal immune response. Through bioinformatics analysis, we examined PEDV S proteins to identify B-cell linear epitopes that meet the criteria of being non-toxic, soluble, antigenic, and capable of neutralizing the virus. In this study, a genetically modified strain of Lactobacillus mucosae G01 (L.mucosae G01) was created by utilizing the S layer protein (SLP) as a scaffold for surface presentation. Chimeric immunodominant epitopes with neutralizing activity were incorporated at various sites on SLP. The successful expression of SLP chimeric immunodominant epitope 1 on the surface of L.mucosae G01 was confirmed through indirect immunofluorescence and transmission electron microscopy, revealing the formation of a transparent membrane. The findings demonstrate that the oral administration of L.mucosae G01, which expresses the SLP chimeric immunodominant gene epitope1, induces the production of secreted IgA in the intestine and feces of mice. Additionally, there is an elevation in IgG levels in the serum. Moreover, the levels of cytokines IL-2, IL-4, IFN-γ, and IL-17 are significantly increased compared to the negative control group. These results suggest that L. mucosae G01 has the ability to deliver exogenous antigens and elicit a specific mucosal immune response against PEDV. This investigation presents new possibilities for immunoprophylaxis against PEDV-induced diarrhea.
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Epítopos de Linfocito B , Lactobacillus , Virus de la Diarrea Epidémica Porcina , Glicoproteína de la Espiga del Coronavirus , Animales , Virus de la Diarrea Epidémica Porcina/inmunología , Ratones , Glicoproteína de la Espiga del Coronavirus/inmunología , Epítopos de Linfocito B/inmunología , Lactobacillus/inmunología , Ratones Endogámicos BALB C , Porcinos , Femenino , Vacunas Virales/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Inmunidad Mucosa , Inmunoglobulina A/inmunología , Glicoproteínas de MembranaRESUMEN
In this research, the diffusion behaviors within the Ti-Fe-Cr ternary system were examined at the temperatures of 1273 K and 1373 K through the diffusion couple technique. This study led to the determination of both ternary inter-diffusion and impurity diffusion coefficients in the body-centered cubic (bcc) phase for the Ti-Fe-Cr alloy, utilizing the Whittle-Green and Hall methods. The statistics show that the average diffusion coefficients DËFeFeTi and DËCrCrTi measured at 1273 K were 1.34 × 10-12 and 3.66 × 10-13, respectively. At 1373 K, the average values of DËFeFeTi and DËCrCrTi were 4.89 × 10-12 and 1.43 × 10-12. By adopting the CALPHAD method, a self-consistent database for atomic mobility in the bcc phase of the Ti-Fe-Cr system was established. This database underwent refinement by comparing the newly acquired diffusion coefficients with data from the existing literature. Diffusion simulations for the diffusion couples were performed, drawing on the established database. The error between the simulated diffusion coefficient and the experimental measurement data is within 15%, and the simulated data of the component distance distribution and diffusion path are in good agreement with the experimental data. The simulations generated results that aligned well with the observed experimental diffusion characteristics, thereby affirming the reliability and accuracy of the database.
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The Rh(III)-catalyzed reaction of aromatic ketoximes with 2-vinylaziridines affords ortho-allylation products of the phenyl rings of aromatic ketoximes in moderate to excellent yields. The reaction requires 0.5 equiv of NaOAc as a base and occurs under mild conditions. The protocol exhibits ortho-monoallylation selectivity, wide scope of substrates, and good compatibility of functional groups.
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Oral behavior management methods include basic behavior management methods and drug behavior management methods. In many cases, dental treatment that cannot be done simply through basic behavior management is not possible. The uncooperative behavior of children with dental fear in oral treatment has increased the demand for medication based behavior management methods. Drug sedation can provide more effective analgesic and anti-anxiety effects, thereby helping to provide comfortable, efficient, and high-quality dental services. This article will review the drug sedation methods selected in clinical treatment of pediatric dental fear in recent years, as well as the safety and effectiveness of commonly used drugs, in order to provide guidance for dental professionals in clinical practice.
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Anestesia Dental , Anestesia , Ansiolíticos , Niño , Humanos , Ansiedad al Tratamiento Odontológico/tratamiento farmacológico , Ansiedad al Tratamiento Odontológico/prevención & control , Terapia Conductista , Sedación ConscienteRESUMEN
As a broad-spectrum antiviral, and especially as a popular drug for treating coronavirus disease 2019 (COVID-19) today, arbidol often involves drug-drug interactions (DDI) when treating critical patients. This study established a rapid and effective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to detect arbidol and its metabolite arbidol sulfoxide (M6-1) levels in vivo and in vitro. In this study, a 200 µL incubation system was used to study the inhibitory effect of the antitumor drug napabucasin on arbidol in vitro, with IC50 values of 2.25, 3.91, and 67.79 µM in rat liver microsomes (RLMs), human liver microsomes (HLMs), and CYP3A4.1, respectively. In addition, we found that the mechanism of inhibition was non-competitive inhibition in RLM and mixed inhibition in HLM. In pharmacokinetic experiments, it was observed that after gavage administration of 48 mg/kg napabucasin and 20 mg/kg arbidol, napabucasin inhibited the metabolism of arbidol in vivo and significantly changed the pharmacokinetic parameters of arbidol, such as AUC(0-t) and AUC(0-∞), in rats. We also found that napabucasin increased the AUC(0-t) and AUC(0-∞) of M6-1, the main metabolite of arbidol. This study provides a reference for the combined use of napabucasin and arbidol in clinical practice.
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An ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method was developed for the determination of tenacissoside G, tenacissoside H, and tenacissoside I in rat plasma. The rat plasma was treated with liquid-liquid extraction using ethyl acetate. The determination was performed on the UPLC HSS T3 column (50 mm × 2.1 mm, 1.8 µm) with a mobile phase consisting of acetonitrile-water (containing 0.1% formic acid) and gradient elution at a flow rate of 0.4 mL/min. Electrospray (ESI) positive ion mode detection and multireaction monitoring (MRM) quantitative analysis were performed. A total of 36 rats were given tenacissoside G, tenacissoside H, and tenacissoside I, respectively, orally (5 mg/kg) and intravenously (1 mg/kg), with 6 rats in each group, to evaluate the pharmacokinetic difference of tenacissoside G, tenacissoside H, and tenacissoside I in rats. The calibration curves showed good linearity in the range of 5-2000 ng/mL, where r was greater than 0.99. The results of precision, accuracy, recovery, matrix effect, and stability met the requirements of biological sample detection methods. The established UPLC-MS/MS method was successfully applied to pharmacokinetic studies of tenacissoside G, tenacissoside H, and tenacissoside I, and the bioavailability was 22.9%, 89.8%, and 9.4%, respectively.
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Vortioxetine is a novel anti-major depression disorder drug with a high safety profile compared with other similar drugs. However, little research has been done on drug-drug interactions (DDI) about vortioxetine. In this paper, the inhibitory effect of vortioxetine on cytochrome P450 (CYP450) and the type of inhibitory mechanism were investigated in human and rat liver microsomes. We set up an in vitro incubation system of 200 µL to measure the metabolism of probe substrates at the present of vortioxetine at 37°C. The concentrations of the metabolites of probe substrates were all measured by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. It was found no time-dependent inhibition (TDI) of vortioxetine through determination of half-maximal inhibitory concentration (IC50) shift values. The enzymes and metabolites involved in this experiment in human and rats were as follows: CYP3A4/CYP3A (midazolam); CYP2B6/CYP2B (bupropion); CYP2D6/CYP2D (dextromethorphan); CYP2C8/CYP2C-1 (amodiaquine); CYP2C9/CYP2C-2 (losartan); and CYP2C19/CYP2C-3 (mephenytoin). We found that vortioxetine competitively inhibited CYP2C19 and CYP2D6 in human liver microsomes (HLMs) with inhibition constant (Ki) values of 2.17 µM and 9.37 µM, respectively. It was noncompetitive inhibition for CYP3A4 and CYP2C8, and its Ki values were 7.26 µM and 6.96 µM, respectively. For CYP2B6 and CYP2C9, vortioxetine exhibited the mixed inhibition with Ki values were 8.55 µM and 4.17 µM, respectively. In RLMs, the type of vortioxetine inhibition was uncompetitive for CYP3A and CYP2D (Ki = 4.41 and 100.9 µM). The inhibition type was competitive inhibition, including CYP2B and CYP2C-2 (Ki = 2.87 and 0.12 µM). The inhibition types of CYP2C-1 and CYP2C-3 (Ki = 39.91 and 4.23 µM) were mixed inhibition and noncompetitive inhibition, respectively. The study of the above mechanism will provide guidance for the safe clinical use of vortioxetine so that the occurrence of DDI can be avoided.
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During the past decade, cognitive neuroscience has been calling for population diversity to address the challenge of validity and generalizability, ushering in a new era of population neuroscience. The developing Chinese Color Nest Project (devCCNP, 2013-2022), the first ten-year stage of the lifespan CCNP (2013-2032), is a two-stages project focusing on brain-mind development. The project aims to create and share a large-scale, longitudinal and multimodal dataset of typically developing children and adolescents (ages 6.0-17.9 at enrolment) in the Chinese population. The devCCNP houses not only phenotypes measured by demographic, biophysical, psychological and behavioural, cognitive, affective, and ocular-tracking assessments but also neurotypes measured with magnetic resonance imaging (MRI) of brain morphometry, resting-state function, naturalistic viewing function and diffusion structure. This Data Descriptor introduces the first data release of devCCNP including a total of 864 visits from 479 participants. Herein, we provided details of the experimental design, sampling strategies, and technical validation of the devCCNP resource. We demonstrate and discuss the potential of a multicohort longitudinal design to depict normative brain growth curves from the perspective of developmental population neuroscience. The devCCNP resource is shared as part of the "Chinese Data-sharing Warehouse for In-vivo Imaging Brain" in the Chinese Color Nest Project (CCNP) - Lifespan Brain-Mind Development Data Community ( https://ccnp.scidb.cn ) at the Science Data Bank.
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Pueblo Asiatico , Encéfalo , Humanos , Encéfalo/diagnóstico por imagen , China , Data Warehousing , Bases de Datos Factuales , NeurocienciasRESUMEN
The rapid development of aquaculture industry has provided a large amount of high-quality animal protein, while the food safety caused by microplastics and nanoplastics (MP/NPs) has become a major concern. In addition, recent evidence has shown the potential toxic effect of PE-MP/NPs, highlighting the need for further research into their environmental and health impacts. Chronic exposure of polyethylene microplastics (PE-MPs) and nanoplastics (PE-NPs) on adult zebrafish were conducted in the present study for 21 d. Organ-dependent oxidative damage induced by MP/NPs was observed. Insignificant differences in neurotoxicity and dysbiosis of gut microbiota were found between MPs and NPs. Changes in glutathione S-transferase (GST), glutathione (GSH), catalase (CAT), lipid peroxidation (LPO), and superoxide dismutase (SOD) showed that MP/NPs induced oxidative damage in gill and intestinal cells of zebrafish. The inhibited AChE activity suggested the potential neurotoxicity of microplastics and nanoplastics (MP/NPs). In addition, chronic exposure increased the alpha-diversity of intestinal microbiota. At the phylum level, the average relative abundance of Proteobacteria increased from 29.73% (control group) to 66.10% (microplastics), 54.84% (nanoplastics) and 60.03% (combined exposure), respectively. Tenericutes decreased from 55.43% (control group) to 20.02% (microplastics), 22.44% (nanoplastics) and 31.77% (combined exposure), respectively. Overall, this study provides new insights and objective evidence for the toxicity assessment of PE-MPs.
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Microbioma Gastrointestinal , Contaminantes Químicos del Agua , Animales , Microplásticos/toxicidad , Microplásticos/metabolismo , Polietileno/metabolismo , Pez Cebra/metabolismo , Plásticos/toxicidad , Contaminantes Químicos del Agua/metabolismo , Estrés Oxidativo , Glutatión/metabolismoRESUMEN
Although inactivated vaccines have higher safety than live-attenuated vaccines in the control of pseudorabies virus (PRV), their protection efficacy is limited due to insufficient immunogenicity when used alone. High-performance adjuvants that can potentiate immune responses are highly desirable to improve the protection efficacy of inactivated vaccines. In this work, we have developed U@PAA-Car, a Carbopol dispersed zirconium-based metal-organic framework UIO-66 modified by polyacrylic acid (PAA), as a promising adjuvant for inactivated PRV vaccines. The U@PAA-Car has good biocompatibility, high colloidal stability, and antigen (vaccine) loading capacity. It significantly potentiates humoral and cellular immune responses over either U@PAA, Carbopol, or commercial adjuvants such as Alum and biphasic 201 by inducing a higher specific antibody titer, IgG2a/IgG1 ratio, cell cytokine secretion, and splenocyte proliferation. A protection rate of over 90% was observed in challenge tests in the model animal mice and the host animal pigs, which is much higher than that observed with commercial adjuvants. The high performance of the U@PAA-Car is attributed to antigen sustainable release at the injection site and highly efficient antigen internalization and presentation. In conclusion, this work not only demonstrates a great potential of the developed U@PAA-Car nano-adjuvant for the inactivated PRV vaccine but also gives a preliminary explanation of its action mechanism. STATEMENT OF SIGNIFICANCE: We have developed a Carbopol dispersed PAA-modified zirconium-based metal-organic framework UIO-66 (U@PAA-Car) as a promising combination nano-adjuvant for the inactivated PRV vaccine. The U@PAA-Car induced higher specific antibody titers and IgG2a/IgG1 ratio, increased cell cytokines secretion, and better splenocyte proliferation than U@PAA, Carbopol, and the commercial adjuvants Alum and biphasic 201, indicating that it induces a significant potentiation of humoral and cellular immune response. In addition, much higher protection rates were achieved with the U@PAA-Car-adjuvanted PRV vaccine in mice and pigs challenge than those observed from the commercial adjuvant groups. This work not only demonstrates the great potential of the U@PAA-Car nano-adjuvant in an inactivated PRV vaccine but also gives a preliminary explanation of its action mechanism.
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Herpesvirus Suido 1 , Estructuras Metalorgánicas , Seudorrabia , Animales , Porcinos , Ratones , Seudorrabia/prevención & control , Circonio/farmacología , Adyuvantes Inmunológicos/farmacología , Inmunidad Celular , Citocinas , Inmunoglobulina G , Vacunas de Productos InactivadosRESUMEN
Thermo-sensitive microgels known as PMO-MGs were synthesized via surfactant free emulsion polymerization, with poly(ethylene glycol) methacrylate (OEGMA475) and 2-(2-methoxyethoxy) ethyl methacrylate (MEO2MA) used as the monomers and N, N-methylene-bis-acrylamide used as the crosslinker. PMO-MGs are spherical in shape and have an average diameter of 323 ± 12 nm, as determined via transmission electron microscopy. PMO-MGs/poly (ether sulfone) (PES) composited ultrafiltration membranes were then successfully prepared via the non-solvent-induced phase separation (NIPS) method using a PMO-MG and PES mixed solution as the casting solution. The obtained membranes were systematically characterized via combined X-ray photoelectron spectroscopy, field-emission scanning electron microscopy, Fourier transform infrared spectroscopy and contact angle goniometer techniques. It was found that the presence of PMO-MGs significantly improved the surface hydrophilicity and antifouling performance of the obtained membranes and the PMO-MGs mainly located on the channel surface of the membranes. At 20 °C, the pure water flux increased from 217.6 L·m-2·h-1 for pure PES membrane (M00) to 369.7 L·m-2·h-1 for PMO-MGs/PES composited membrane (M20) fabricated using the casting solution with 20-weight by percentage microgels. The incorporation of PMO-MGs also gave the composited membranes a thermo-sensitive character. When the temperature increased from 20 to 45 °C, the pure water flux of M20 membrane was enhanced from 369.7 to 618.7 L·m-2·h-1.
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Chromic materials play a decisive and escalating role in information security. However, it is challenging to develop chromic materials for encryption technologies that can hardly be imitated. Inspired by versatile metachrosis in nature, a series of coumarin-based 7-(6-bromohexyloxy)-coumarin microgel colloidal crystals (BrHC MGCC) with multiresponsive chromism are able to be assembled by ionic microgels in poly(vinyl alcohol) (PVA) solution followed by two cycles of freezing-thawing. The ionic microgels can be finely tailored by in situ quaternization with tunable size under varied temperatures and hydration energies of counterions as well as quenched luminescence under UV irradiation, which endows BrHC MGCC with intriguing chromism in the dual-channel coloration of physical structural color and chemical fluorescent color. Three types of BrHC MGCC exhibit various change ranges in structural coloration and similar quenching in fluorescence emission, which can be utilized for the development of the static-dynamic combined anticounterfeiting system with dual coloration. The information conveyed by the BrHC MGCC array presents dynamic variation versus temperature, while the static information can be only integrally read in both sunlight and a 365 nm UV lamp. The fabrication of a microgel colloidal crystal with dual coloration opens a facile and ecofriendly window for multilevel information security, camouflage, and a cumbersome authentication process.
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As the validated agent for the treatment of chronic myelogenous leukemia (CML), flumatinib is a novel oral tyrosine kinase inhibitor (TKI) with higher potency and selectivity for BCR-ABL1 kinase compared to imatinib. Many patients experience aspergillosis infection and they may start using isavuconazole, which is an inhibitor of CYP3A4. However, there is no study on their interaction in vitro and in vivo. In the present study, the concentrations of flumatinib and its major metabolite M1 were rapidly determined using an stable ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. The half-maximal inhibitory concentration (IC50) was 6.66 µM in human liver microsomes (HLM), while 0.62 µM in rat liver microsomes (RLM) and 2.90 µM in recombinant human CYP3A4 (rCYP3A4). Furthermore, the mechanisms of inhibition of flumatinib in human liver microsomes, rat liver microsomes and rCYP3A4 by isavuconazole were mixed. Moreover, ketoconazole, posaconazole, and isavuconazole showed more potent inhibitory effects than itraconazole, fluconazole, and voriconazole on HLM-mediated flumatinib metabolism. In pharmacokinetic experiments of rats, it was observed that isavuconazole could greatly change the pharmacokinetic parameters of flumatinib, including AUC(0-t), AUC(0-∞), Cmax and CLz/F, but had no effect on the metabolism of M1. According to the results of in vitro and in vivo studies, the metabolism of flumatinib was inhibited by isavuconazole, suggesting that isavuconazole may raise the plasma concentration of flumatinib. Thus, it is important to take special care of the interactions between flumatinib and isavuconazole in clinical applications.
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Ponazuril is a triazine anticoccidial drug which is the main metabolite of toltrazuril in animals, it has excellent activity against many protozoa, including Cystoisospora suis, and has broad application prospects in the control of swine coccidiosis. To evaluate the pharmacokinetic and excretion characteristics of ponazuril, 12 healthy piglets aged 10-14 days were divided into 2 groups for pharmacokinetic studies, which were given 20 mg/kg body weight ponazuril orally and intravenously, respectively. And 6 other piglets were housed individually in metabolic cages and given the same oral dose of ponazuril. After administration, the concentration of ponazuril in plasma, fecal, and urine samples collected was determined using high-performance liquid chromatography (HPLC). The plasma concentration profiles of ponazuril obtained after intravenous and oral administration were analyzed simultaneously by the nonlinear mixed-effects (NLME) model. Following the results, the pharmacokinetics of ponazuril exhibited a Michaelis-Menten elimination with Michaelis-Menten constant Km and maximum metabolic rate Vm of 10.8 µg/mL and 0.083 mg/kg/h. The apparent volume of distribution was calculated to be 735 mL/kg, and the final estimated oral bioavailability was 81%. Besides, cumulatively 86.42 ± 2.96% of ponazuril was recovered from feces and 0.31% ± 0.08% from urine during 0-1,020 h after oral administration. These findings indicated a good oral absorption of ponazuril in piglets with nonlinear disposition and slow excretion largely via feces, implying sustained drug concentration in vivo and long-lasting anticoccidial effects.
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The COVID-19 pandemic has caused dramatic death and infection worldwide, leading to a global public health crisis. As for precautions, scientists have different opinions on the effectiveness of masks in preventing COVID-19 transmission. Published studies suggested that medical masks may help in preventing respiratory virus infection. But the currently available experimental results are too preliminary to support an informed policy. In conclusion, we need more well-designed and robust research on the effectiveness of masks in preventing COVID-19 infection.
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The proposal of the aggregation-induced emission (AIE) effect shines a light on the practical application of luminescent materials. The AIE-active luminescence microgels (TPEC MGs) with photo-induced color-changing behavior were developed by integrating positively charged AIE luminogens (AIEgens) into the anionic network of microgels, where AIEgens of TPEC were obtained from the quaternization reaction between tetra-(4-pyridylphenyl)ethylene (TPE-4Py) and 7-(6-bromohexyloxy)-coumarin. The aqueous suspensions of TPEC MGs exhibit a significant AIE effect following the enhancement of quantum yield. In addition, further increase in fluorescence intensity and blueshift occur at elevated temperatures due to the collapse of microgels. The distinctive photochromic behavior of TPEC MGs was observed, which presents as the transition from orange-yellow to blue-green color under UV irradiation, which is different from TPEC in good organic solvents. The phenomenon of color changing can be ascribed to the competition between photodimerization of the coumarin part and photocyclization of TPE-4Py in TPEC. The photochromic TPEC MG aqueous suspensions can be conducted as aqueous microgel inks for information display, encryption, and dynamic anticounterfeiting.
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BACKGROUND: Shigella flexneri (S. flexneri) is a major pathogen causing acute intestinal infection, but the systematic oxidative damage incurred during the course of infection has not been investigated. AIM: To investigate the incurred systemic RNA oxidative damage and the diagnostic value of RNA oxidative metabolites during S. flexneri-induced intestinal infection. METHODS: In this study, a Sprague-Dawley rat model of acute intestinal infection was established by oral gavage with S. flexneri strains. The changes in white blood cells (WBCs) and cytokine levels in blood and the inflammatory response in the colon were investigated. We also detected the RNA and DNA oxidation in urine and tissues. RESULTS: S. flexneri infection induced an increase in WBCs, C-reactive protein, interleukin (IL)-6, IL-10, IL-1ß, IL-4, IL-17a, IL-10, and tumor necrosis factor α (TNF-α) in blood. Of note, a significant increase in urinary 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn), an important marker of total RNA oxidation, was detected after intestinal infection (P = 0.03). The urinary 8-oxo-Gsn level returned to the baseline level after recovery from infection. In addition, the results of a correlation analysis showed that urinary 8-oxo-Gsn was positively correlated with the WBC count and the cytokines IL-6, TNF-α, IL-10, IL-1ß, and IL-17α. Further detection of the oxidation in different tissues showed that S. flexneri infection induced RNA oxidative damage in the colon, ileum, liver, spleen, and brain. CONCLUSION: Acute infection induced by S. flexneri causes increased RNA oxidative damage in various tissues (liver, spleen, and brain) and an increase of 8-oxo-Gsn, a urinary metabolite. Urinary 8-oxo-Gsn may be useful as a biomarker for evaluating the severity and prognosis of infection.