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Listeriosis is highly prevalent in the animal farming industry, with Listeria monocytogenes as the causative pathogen. To identify potential therapeutic targets for LM infection, we investigated the mechanisms of LM infection in goat uteri. We inoculated a group of goats with LM via jugular vein injection, isolated and raised them, and subsequently collected sterile samples of their uterine tissue after they exhibited clinical symptoms of LM infection. We used Giemsa staining, immunohistochemical staining, real-time qPCR, and Western blotting as experimental methods.First, we investigated the mechanism of Listeria monocytogenes (LM) infection in the goat uterus by examining the expression levels of listeriolysin O, E-cadherin, and tyrosine kinase c-Met in the uterus.Furthermore, we investigated the impact of LM infection on uterine autophagy and cell apoptosis. The results indicate that the injection of LM into the goats' jugular veins leads to LM infection in the goats' uteri. During LM survival inside the goat uterine cells, there is a significant increase in the expression levels of LLO, E-cadherin, and c-Met in the host uterine tissue. This suggests that LM may potentially infect goat uteri through the InlA/E-cadherin and InlB/c-Met pathways. Furthermore, LM infection increases the levels of apoptosis and autophagy in goat uteri. Apoptosis genes Bcl-2 and Bax, as well as autophagy-related genes LC3B, PINK1, and Parkin, exhibit varying degrees of changes in localization and expression in goat uteri, mediating the occurrence of apoptotic and autophagic responses.
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H9N2 avian influenza poses a significant public health risk, necessitating effective vaccines for mass immunization. Oral inactivated vaccines offer advantages like the ease of administration, but their efficacy often requires enhancement through mucosal adjuvants. In a previous study, we established a novel complex of polysaccharide from Atractylodes macrocephala Koidz binding with zinc oxide nanoparticles (AMP-ZnONPs) and preliminarily demonstrated its immune-enhancing function. This work aimed to evaluate the efficacy of AMP-ZnONPs as adjuvants in an oral H9N2-inactivated vaccine and the vaccine's impact on intestinal mucosal immunity. In this study, mice were orally vaccinated on days 0 and 14 after adapting to the environment. AMP-ZnONPs significantly improved HI titers, the levels of specific IgG, IgG1 and IgG2a in serum and sIgA in intestinal lavage fluid; increased the number of B-1 and B-2 cells and dendritic cell populations; and enhanced the mRNA expression of intestinal homing factors and immune-related cytokines. Interestingly, AMP-ZnONPs were more likely to affect B-1 cells than B-2 cells. AMP-ZnONPs showed mucosal immune enhancement that was comparable to positive control (cholera toxin, CT), but not to the side effect of weight loss caused by CT. Compared to the whole-inactivated H9N2 virus (WIV) group, the WIV + AMP-ZnONP and WIV + CT groups exhibited opposite shifts in gut microbial abundance. AMP-ZnONPs serve as an effective and safe mucosal adjuvant for oral WIV, improving cellular, humoral and mucosal immunity and microbiota in the gastrointestinal tract, avoiding the related undesired effects of CT.
Assuntos
Atractylodes , Vírus da Influenza A Subtipo H9N2 , Vacinas contra Influenza , Óxido de Zinco , Animais , Camundongos , Adjuvantes Imunológicos/farmacologia , Imunidade nas Mucosas , Vacinas de Produtos Inativados , Polissacarídeos/farmacologia , Anticorpos AntiviraisRESUMO
The avian influenza virus is infected through the mucosal route, thus mucosal barrier defense is very important. While the inactivated H9N2 vaccine cannot achieve sufficient mucosal immunity, adjuvants are needed to induce mucosal and systemic immunity to prevent poultry from H9N2 influenza virus infection. Our previous study found that polysaccharide from Atractylodes macrocephala Koidz binding with zinc oxide nanoparticles (AMP-ZnONPs) had immune-enhancing effects in vitro. This study aimed to evaluate the mucosal immune responses of oral whole-inactivated H9N2 virus (WIV)+AMP-ZnONPs and its impact on the animal challenge protection, and the corresponding changes of pulmonary metabolomics after the second immunization. The results showed that compared to the WIV, the combined treatment of WIV and AMP-ZnONPs significantly enhanced the HI titer, IgG and specific sIgA levels, the number of goblet cells and intestinal epithelial lymphocytes (iIELs) as well as the expression of J-chain, polymeric immunoglobulin receptor (pIgR), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α) and transforming growth factor-ß (TGF-ß). In viral attack experiments, WIV combing with AMP-ZnONPs effectively reduced lung damage and viral titers in throat swabs. Interestingly, significant changes of both the IgA intestinal immune network and PPAR pathway could also be found in the WIV+AMP-ZnONPs group compared to the non-infected group. Taken together, these findings suggest that AMP-ZnONPs can serve as a potential mucosal vaccine adjuvant, thereby avoiding adverse stress and corresponding costs caused by vaccine injection.
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Vírus da Influenza A Subtipo H9N2 , Vacinas contra Influenza , Influenza Aviária , Vacinas , Animais , Imunidade nas Mucosas , Galinhas , Anticorpos Antivirais , Adjuvantes Imunológicos/farmacologia , Administração Oral , Vacinas de Produtos Inativados , Influenza Aviária/prevenção & controleRESUMO
Domperidone is a powerful peripheral dopamine receptor antagonist; however, a systematic review of the synthetic methods and processes of this drug has not been reported so far. This review summarizes the synthetic strategies, synthetic routes and reaction processes of domperidone in detail. Domperidone can be synthesized from the coupling reaction of two benzimidazolone derivatives (intermediates 1 and 2). Intermediate 1 can be prepared by two synthetic routes: the cyclization of o-phenylenediamine with carbonyl reagents followed by coupling with 1,3-dihalopropane, and the coupling reaction of o-halo or o-amino substituted nitrobenzene with 1,3-disubstituted propane followed by reduction and cyclization. The latter route avoids the production of di-substituted by-products and has higher reaction selectivity. Intermediate 2 is synthesized by coupling substituted nitrobenzene with 4-aminopiperidine followed by reduction and cyclization, which is similar to the synthetic route of intermediate 1. Understanding the advantages and drawbacks of these synthetic methodologies would provide insights for the development of new strategies to prepare domperidone. Moreover, the methods used to synthesize domperidone can provide alternative approaches in the preparation of drugs or compounds with similar structure.
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An efficient and catalyst-free methodology for the reductive cyclization of various disulfides using BH3NH3 as a reductant and CO2 as a C1 resource was developed. The desired 2-unsubstituted benzothiazole derivatives were obtained in good to excellent yields. Moreover, mechanism investigation demonstrated that BH3NH3 played an important role in the formation of benzothiazole. As a reducing agent, BH3NH3 reduced CO2 and cleaved the S-S bond of the disulfide efficiently. In addition, the N-H bond of the amino group was also activated by BH3NH3. To the best of our knowledge, this is an unprecedented catalyst-free protocol for the synthesis of 2-unsubstituted benzothiazole from bis(2-aminophenyl) disulfide and CO2.
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Abstract The main purpose of this work was to compare the effects of the four preparation methods on the TFLX/HP-β-CD inclusion complex. The effects of different preparation methods on the inclusion complex were investigated by SEM, DSC, PXRD, FT-IR and 1H NMR. All the characterization information indicated that the four preparation methods could cause interaction between TFLX and HP-β-CD, but the inclusion complex prepared by solvent evaporation has more reaction sites. Phase solubility experiments demonstrated that the inclusion reaction was spontaneous. In vitro dissolution experiments showed that the dissolution of the inclusion complex in water was: solvent evaporation method (64.39%) > grinding method (42.37%) > ultrasonic method (40.00%) > freezing method (36.08%), and all higher than pure TFLX and physical mixture. These results suggest that the solvent evaporation is the most suitable method for preparing TFLX/HP-β-CD inclusion complexes.
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A novel compound biotinylated emodin was synthesized by a two-step acyl chloride method which connects the biotin to emodin with esterification reaction. The product was characterized with ultraviolet-visible spectrophotometry, fourier transform infrared and high-performance liquid chromatography tandem mass spectrometry techniques. Its antibacterial activity against Staphylococcus aureus CMCC 26003 was investigated, and the emodin- and biotinylated emodin-caused antibacterial mechanism was proposed. It was shown that the product was isolated and activity of emodin was remained. These results indicated that our study provides a kind of chemosynthesis method under mild conditions and a strong molecular tool for investigating the emodin-binding protein.
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Antibacterianos/síntese química , Antibacterianos/metabolismo , Emodina/síntese química , Emodina/metabolismo , Antraquinonas , Antibacterianos/química , Antibacterianos/farmacologia , Biotinilação , Cromatografia Líquida , Emodina/química , Emodina/farmacologia , Esterificação , Espectrofotometria Ultravioleta , Staphylococcus aureus/efeitos dos fármacosRESUMO
We demonstrate the improvement and formation of UV-induced damage on LBO crystal output surface during long-term (130 h) high-power (20 W) high-repetition-rate (80 kHz) third-harmonic generation. The output surface was super-polished (RMS surface roughness <0.6 nm) to sub-nanometer scale super smooth roughness. The surface lifetime has been improved more than 20-fold compared with the as-polished ones (RMS surface roughness 4.0~8.0 nm). The damage could be attributed to the consequence of thermal effects resulted from impurity absorptions. Simultaneously, it was verified that the impurities originated in part from the UV-induced deposition.
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Boratos/química , Boratos/efeitos da radiação , Compostos de Lítio/química , Compostos de Lítio/efeitos da radiação , Raios Ultravioleta , Teste de Materiais , Propriedades de Superfície/efeitos da radiaçãoRESUMO
This paper presents the concept of constant-fluence amplification. It refers to the fact that laser fluence anywhere in the amplifier gain medium is identical to the design fluence E(design), which represents the maximum allowed fluence in consideration of the laser-induced damage threshold (LIDT). Based on this concept, we explore ideal amplifier model (IAM) and near-ideal amplifier chain (NIAC) and propose an optimal NIAC design method and analytically offer an indicator of the extraction efficiency. Finally, the paper discusses the influences of losses on the NIAC's extraction efficiency.
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A compact, high-power, high-repetition-rate Q-switched laser oscillator is presented in this paper. Adopting the acousto-optics Q-switching mechanism, the maximum output power of 57 W of 1064 nm fundamental wave at 200 kHz is obtained under 110 W 888 nm pumping. The stable working range extends from 30 to 250 kHz, while the beam quality factor M(2) is smaller than 1.30. Subsequently, based on the 42 W of fundamental wave with the beam quality better than 1.10, 29.5 W of 532 nm green laser and 18 W of 355 nm ultraviolet wave are achieved.