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Under the wave of Industry 4.0, traditional pharmaceutical manufacturing enterprises are in urgent need of intelligent manufacturing transformation and upgrading, and exploring the optimal realization path of intelligent manufacturing transformation can help accelerate the transformation process of pharmaceutical manufacturing enterprises. This paper uses grounded theory research methods to conduct a multi-case study to summarize six influencing factors of the intelligent manufacturing transformation of Chinese pharmaceutical manufacturing enterprises; and then analyzes the correlation between the intelligent manufacturing influencing factors based on the DEMATEL method and the NK model, and identifies the key influencing factors according to this, and then draws the fitness landscape map of the intelligent manufacturing transformation, and finally arrives at the optimal path selection of the intelligent manufacturing transformation of pharmaceutical manufacturing enterprises. The study enriches and extends the research paradigm of intelligent manufacturing transformation, and provides lessons for pharmaceutical manufacturing enterprises to realize intelligent manufacturing transformation and upgrading.
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Industria Farmacéutica , Humanos , Simulación por Computador , China , Tecnología Farmacéutica/métodos , Modelos TeóricosRESUMEN
BACKGROUND: The Pseudorabies Virus (PRV) leading to pseudorabies and causes huge economic losses in pig industry. The development of novel PRV variations has diminished the efficacy of traditional vaccinations, and there is yet no medication that can stop the spread of PRV infection. Therefore, PRV eradication is challenging. Oregano essential oil, the plant-based ingredient for medication feed have been shown to has strong anti-herpesvirus activity, but no anti-PRV function has been reported. RESULTS: The current study assessed the anti-pseudorabies virus (PRV) activity of oregano essential oil and explored its mechanisms and most effective components against PRV. Our in vivo findings demonstrated that oregano essential oil could decrease the PRV load in tissues, mitigate tissue lesions, and enhance the survival rate of mice. The potential antiviral mechanism involves augmenting humoral and cellular immune responses in PRV-infected mice. To further investigate the most effective components of oregano essential oil against PRV, an in vitro study was conducted, revealing that oregano essential oil and its main constituents, carvacrol and thymol, all diminished PRV intracellular proliferation in vitro. Carvacrol exhibited the most potent anti-PRV effect, serving as the primary contributor to oregano essential oil's anti-PRV activity. The mechanisms underlying carvacrol's anti-PRV properties include the upregulation of cytokines TNF-α, IFN-ß, IFN-γ, IL-12, and the inhibition of PRV-induced apoptosis in BHK-21 cells. CONCLUSIONS: Our study provides an effective drug for the prevention and control of PRV infection.
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Antivirales , Herpesvirus Suido 1 , Aceites Volátiles , Origanum , Seudorrabia , Animales , Aceites Volátiles/farmacología , Origanum/química , Ratones , Herpesvirus Suido 1/efectos de los fármacos , Antivirales/farmacología , Seudorrabia/tratamiento farmacológico , Seudorrabia/virología , Cimenos/farmacología , Timol/farmacología , Citocinas/metabolismo , Línea Celular , Inmunidad Celular/efectos de los fármacos , Inmunidad Humoral/efectos de los fármacos , Femenino , Ratones Endogámicos BALB C , Carga Viral/efectos de los fármacos , Porcinos , Modelos Animales de Enfermedad , Aceites de Plantas/farmacologíaRESUMEN
Under the impetus of the new industrial revolution, how to realize intelligent manufacturing transformation of traditional pharmaceutical manufacturing enterprises has realistic urgency. The study starts from the perspective of complex adaptive system, constructs a system dynamics model of the evolution mechanism of intelligent manufacturing transformation of pharmaceutical manufacturing enterprises based on technological adaptation and evolutionary adaptation, and analyzes it by simulation using Vensim PLE software. The results of the study show that pharmaceutical manufacturing enterprises utilize technological affordances to provide support to realize network product-based manufacturing capability and smart product-based manufacturing capability through technological innovation capability and institutional optimization capability; the technological affordances environment promotes the realization of intelligent manufacturing transformation of pharmaceutical manufacturing enterprises to present a stage transformation law. The study enriches and extends the research paradigm of intelligent manufacturing transformation, and provides a reference for pharmaceutical manufacturing enterprises to realize intelligent manufacturing transformation.
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Diseases caused by viruses pose a significant risk to the health of aquatic animals, for which there are presently no efficacious remedies. Interferon (IFN) serving as an antiviral agent, is frequently employed in clinical settings. Due to the unique living conditions of aquatic animals, traditional injection of interferon is cumbersome, time-consuming and labor-intensive. This study aimed to prepare IFN microcapsules through emulsion technique by using resistant starch (RS) and carboxymethyl chitosan (CMCS). Optimization was achieved using the Box-Behnken design (BBD) response surface technique, followed by the creation of microcapsules through emulsification. With RS at a concentration of 1.27 %, a wateroxygen ratio of 3.3:7.4, CaCl2 at 13.67 %, CMCS at 1.04 %, the rate of encapsulation can escalate to 80.92 %. Rainbow trout infected with Infectious hematopoietic necrosis virus (IHNV) and common carp infected with Spring vireemia (SVCV) exhibited a relative survival rate (RPS) of 65 % and 60 % after treated with IFN microcapsules, respectively. Moreover, the microcapsules effectively reduced the serum AST levels and enhanced the expression of IFNα, IRF3, ISG15, MX1, PKR and Viperin in IHNV-infected rainbow trout and SVCV-infected carp. In conclusion, this integrated IFN microcapsule showed potential as an antiviral agent for treatment of viral diseases in aquaculture.
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Interferón-alfa , Oncorhynchus mykiss , Proteínas Recombinantes , Animales , Oncorhynchus mykiss/virología , Interferón-alfa/farmacología , Proteínas Recombinantes/farmacología , Cápsulas , Antivirales/farmacología , Antivirales/química , Composición de Medicamentos , Quitosano/química , Quitosano/análogos & derivados , Virus de la Necrosis Hematopoyética Infecciosa/efectos de los fármacos , Sistemas de Liberación de Medicamentos , Enfermedades de los Peces/virología , Enfermedades de los Peces/tratamiento farmacológicoRESUMEN
Infection with Vibrio mimicus in the Siluriformes has demonstrated a rapid and high infectivity and mortality rate, distinct from other hosts. Our earlier investigations identified necrosis, an inflammatory storm, and tissue remodeling as crucial pathological responses in yellow catfish (Pelteobagrus fulvidraco) infected with V. mimicus. The objective of this study was to further elucidate the impact linking these pathological responses within the host during V. mimicus infection. Employing metabolomics and transcriptomics, we uncovered infection-induced dense vacuolization of perimysium; Several genes related to nucleosidase and peptidase activities were significantly upregulated in the skin and muscles of infected fish. Concurrently, the translation processes of host cells were impaired. Further investigation revealed that V. mimicus completes its infection process by enhancing its metabolism, including the utilization of oligopeptides and nucleotides. The high susceptibility of yellow catfish to V. mimicus infection was associated with the composition of its body surface, which provided a microenvironment rich in various nucleotides such as dIMP, dAMP, deoxyguanosine, and ADP, in addition to several amino acids and peptides. Some of these metabolites significantly boost V. mimicus growth and motility, thus influencing its biological functions. Furthermore, we uncovered an elevated expression of gangliosides on the surface of yellow catfish, aiding V. mimicus adhesion and increasing its infection risk. Notably, we observed that the skin and muscles of yellow catfish were deficient in over 25 polyunsaturated fatty acids, such as Eicosapentaenoic acid, 12-oxo-ETE, and 13-Oxo-ODE. These substances play a role in anti-inflammatory mechanisms, possibly contributing to the immune dysregulation observed in yellow catfish. In summary, our study reveals a host immune deviation phenomenon that promotes bacterial colonization by increasing nutrient supply. It underscores the crucial factors rendering yellow catfish highly susceptible to V. mimicus, indicating that host nutritional sources not only enable the establishment and maintenance of infection within the host but also aid bacterial survival under immune pressure, ultimately completing its lifecycle.
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Bagres , Enfermedades de los Peces , Vibriosis , Vibrio mimicus , Animales , Bagres/inmunología , Bagres/genética , Enfermedades de los Peces/inmunología , Enfermedades de los Peces/microbiología , Vibriosis/veterinaria , Vibriosis/inmunología , Vibrio mimicus/inmunología , Susceptibilidad a Enfermedades/veterinaria , Susceptibilidad a Enfermedades/inmunología , Epidermis/inmunología , Epidermis/microbiología , NutrientesRESUMEN
The immune system of bony fish closely resembles that of mammals, comprising both specific (adaptive) and non-specific (innate) components. Notably, the mucosa-associated lymphoid tissue (MALT) serves as the first line of defense within the non-specific immune system, playing a critical role in protecting these aquatic organisms against invading pathogens. MALT encompasses a network of immune cells strategically distributed throughout the gills and intestines, forming an integral part of the mucosal barrier that interfaces directly with the surrounding aquatic environment. Spring Viremia of Carp Virusï¼SVCVï¼, a highly pathogenic agent causing substantial harm to common carp populations, has been designated as a Class 2 animal disease by the Ministry of Agriculture and Rural Affairs of China. Utilizing a comprehensive array of research techniques, including Hematoxylin and Eosin (HE)ãAlcian Blue Periodic Acid-Schiff (AB-PAS)ãtranscriptome analysis for global gene expression profiling and Reverse Transcription-Polymerase Chain Reaction (RT-qPCR), this study uncovered several key findings: SVCV is capable of compromising the mucosal architecture in the gill and intestinal tissues of carp, and stimulate the proliferation of mucous cells both in gill and intestinal tissues. Critically, the study revealed that SVCV's invasion elicits a robust response from the carp's mucosal immune system, demonstrating the organism's capacity to resist SVCV invasion despite the challenges posed by the pathogen.
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Carpas , Enfermedades de los Peces , Perfilación de la Expresión Génica , Branquias , Intestinos , Infecciones por Rhabdoviridae , Rhabdoviridae , Animales , Branquias/inmunología , Branquias/virología , Rhabdoviridae/fisiología , Enfermedades de los Peces/inmunología , Enfermedades de los Peces/virología , Carpas/inmunología , Carpas/genética , Perfilación de la Expresión Génica/veterinaria , Infecciones por Rhabdoviridae/inmunología , Infecciones por Rhabdoviridae/veterinaria , Infecciones por Rhabdoviridae/virología , Intestinos/inmunología , Intestinos/virología , Inmunidad Innata/genética , Transcriptoma/inmunología , Inmunidad MucosaRESUMEN
TonB-dependent siderophore receptors play a critical transport role for Flavobacterium columnare virulence formation and growth, and have become valuable targets for the development of novel antimicrobial agents. Traditional Chinese medicine has demonstrated notable efficacy in the treatment of fish diseases and includes potential antibacterial agents. Herein, we performed molecular docking-based virtual screening to discover novel TonB-dependent siderophore receptor inhibitors from traditional Chinese medicine and provide information for developing novel antibacterial agents. Firstly, we efficiently obtained 11 potential inhibitors with desirable drug-like characteristics from thousands of compounds in the TCM library based on virtual screening and property prediction. The antibacterial activity of Enoxolone, along with its interaction characteristics, were determined via an MIC assay and molecular dynamic simulation. Transcriptional profiling, along with validation experiments, subsequently revealed that an insufficient uptake of iron ions by bacteria upon binding to the TonB-dependent siderophore receptors is the antibacterial mechanism of Enoxolone. Finally, Enoxolone's acceptable toxicity was illustrated through immersion experiments. In summary, we have used virtual screening techniques for the first time in the development of antimicrobial agents in aquaculture. Through this process, we have identified Enoxolone as a promising compound targeting the TonB-dependent siderophore receptor of F. columnare. In addition, our findings will provide new ideas for the advancement of innovative antimicrobial medications in aquaculture.
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In this work, thermo-oxidative behavior, kinetic triplet, and free radical mechanism of ultraheavy oil during an in situ combustion (ISC) process were systematically surveyed via multiple thermal analysis techniques (TG/DTG/DSC/PDSC), model-free methods, and related mathematical simulation. First, specific mass loss, exothermic intensity, and corresponding temperature intervals were respectively determined in low-/high-temperature oxidation (LTO/HTO) regions. In addition, the comparison of atmospheric/pressurized differential scanning calorimetry (DSC/PDSC) experiments indicated that the pressurized conditions could obviously strengthen the oxidation progress with more heat emission. Then two model-free methods were contrastively employed for PDSC data to calculate LTO and HTO activation energy variations with the conversion rate. Moreover, the acceleratory rate model for LTO and the Sestak-Berggren model for HTO were accordingly picked as the most probable mechanism functions, which were later used to determine the simulated curves. Then, the simulations of α-T and dα/dT-T curves were respectively attained using Friedman equation in MATLAB software and contrasted with experimental data to validate the accuracy of the yielded kinetic triplet and forecast the combustion behavior. Further, the evolution pathways of the underlying oxidation mechanism was illustrated. This study updates the understanding of the nonisothermal combustion process, contributing to the subsequent numerical simulation and feasible investigation for in situ combustion implementation to enhance heavy oil recovery.
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This study presents experimental evidence of the dependence of non-radiative recombination processes on the electron-phonon coupling of perovskite in perovskite solar cells (PSCs). Via A-site cation engineering, a weaker electron-phonon coupling in perovskite has been achieved by introducing the structurally soft cyclohexane methylamine (CMA+) cation, which could serve as a damper to alleviate the mechanical stress caused by lattice oscillations, compared to the rigid phenethyl methylamine (PEA+) analog. It demonstrates a significantly lower non-radiative recombination rate, even though the two types of bulky cations have similar chemical passivation effects on perovskite, which might be explained by the suppressed carrier capture process and improved lattice geometry relaxation. The resulting PSCs achieve an exceptional power conversion efficiency (PCE) of 25.5% with a record-high open-circuit voltage (VOC) of 1.20 V for narrow bandgap perovskite (FAPbI3). The established correlations between electron-phonon coupling and non-radiative decay provide design and screening criteria for more effective passivators for highly efficient PSCs approaching the Shockley-Queisser limit.
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[This corrects the article DOI: 10.3389/fmicb.2023.1295065.].
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Vibrio mimicus is a serious pathogen in aquatic animals, resulting in significant economic losses. The cAMP receptor protein (CRP) often acts as a central regulator in highly pathogenic pathogens. V. mimicus SCCF01 is a highly pathogenic strain isolated from yellow catfish; the crp gene deletion strain (Δcrp) was constructed by natural transformation to determine whether this deletion affects the virulence phenotypes. Their potential molecular connections were revealed by qRT-PCR analysis. Our results showed that the absence of the crp gene resulted in bacterial and colony morphological changes alongside decreases in bacterial growth, hemolytic activity, biofilm formation, enzymatic activity, motility, and cell adhesion. A cell cytotoxicity assay and animal experiments confirmed that crp contributes to V. mimicus pathogenicity, as the LD50 of the Δcrp strain was 73.1-fold lower compared to the WT strain. Moreover, qRT-PCR analysis revealed the inhibition of type II secretion system genes, flagellum genes, adhesion genes, and metalloproteinase genes in the deletion strain. This resulted in the virulence phenotype differences described above. Together, these data demonstrate that the crp gene plays a core regulatory role in V. mimicus virulence and pathogenicity.
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As an ancient species with both conservation and commercial value, Sturgeon's inflammatory regulation mechanism is a research point. Nucleotide-binding and oligomerization domain-containing proteins 1 and 2 (NOD1/2) are classical intracellular pattern recognition receptors (PRRs) in immunity of anti-bacterial infection. However, the characterization and function of NOD1/2 in Sturgeon are still unclear. In this study, we analyzed the synteny relationship of NOD1/2 genes between Acipenser ruthenus and representative fishes at the genome-level. Results showed that the ArNOD2 collinear genes pair was present in all representative fishes. The duplicated ArNOD1/2 genes were under purifying selection during evolution as indicated by their Ka/Ks values. To explore the function of NOD1/2, we further investigated their expression patterns and the effects of pathogenic infection, PAMPs treatment, and siRNA interference in Acipenser baerii, the sibling species of A. ruthenus. Results showed that both AbNOD1/2 were expressed at early developmental stages and in different tissues. Pathogenic infection in vivo and PAMPs treatment in vitro demonstrated that AbNOD1/2 could respond to pathogen stimulation. siRNA interference with AbNOD1/2 inhibited expression levels of RIPK2 and inflammatory cytokines compared to the control group after iE-DAP or MDP treatment. This study hinted that the AbNOD1/2 could stimulate the inflammatory cytokines response during evolutionary processes.
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Infecciones Bacterianas , Moléculas de Patrón Molecular Asociado a Patógenos , Animales , Peces/genética , Citocinas , ARN Interferente Pequeño , Proteína Adaptadora de Señalización NOD1/genética , Proteína Adaptadora de Señalización NOD2/genéticaRESUMEN
The intestinal microbiota interacts with the host and plays an important role in the immune response, digestive physiology, and regulation of body functions. In addition, it is also well documented that the intestinal microbiota of aquatic animals are closely related to their growth rate. However, whether it resulted in different sizes of crayfish in the rice-crayfish coculture model remained vague. Here, we analyzed the intestinal microbiota characteristics of crayfish of three sizes in the same typical rice-crayfish coculture field by high-throughput sequencing technology combined with quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme activity, investigating the relationship between intestinal microbiota in crayfish and water and sediments. The results showed that the dominant intestinal microbiota of crayfish was significantly different between the large size group (BS), normal size group (NS), and small size group (SS), where Bacteroides and Candidatus_Bacilloplasma contributed to the growth of crayfish by facilitating food digestion through cellulolysis, which might be one of the potential factors affecting the difference in sizes. Follow-up experiments confirmed that the activity of lipase (LPS) and protease was higher in BS, and the relative expression of development-related genes, including alpha-amylase (α-AMY), myocyte-specific enhancer factor 2a (MEF2a), glutathione reductase (GR), chitinase (CHI), and ecdysone receptor (EcR), in BS was significantly higher than that in SS. These findings revealed the intestinal microbiota characteristics of crayfish of different sizes and their potential impact on growth, which is valuable for managing and manipulating the intestinal microbiota in crayfish to achieve high productivity in practice. KEY POINTS: ⢠Significant differences in the dominant microflora of BS, NS, and SS in crayfish. ⢠Cellulolysis might be a potential factor affecting different sizes in crayfish. ⢠Adding Bacteroides and Candidatus_Bacilloplasma helped the growth of crayfish.
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Microbioma Gastrointestinal , Microbiota , Oryza , Animales , Astacoidea , Alimentos Marinos , BacteroidesRESUMEN
Sichuan is a significant aquaculture province in China, with a total aquaculture output of 1.72 × 106 tons in 2022. One of the most significant microorganisms hurting the Sichuan aquaculture is Aeromonas hydrophila, whose genotype and antibiotic resistance are yet unknown. This study isolated a total of 64 strains of A. hydrophila from various regions during September 2019 to June 2021 within Sichuan province, China. The technique of Multi-Locus Sequence Typing (MLST) was used for the purpose of molecular typing. Meanwhile, identification of antibiotic resistance phenotype and antibiotic resistance gene was performed. The findings of the study revealed that 64 isolates exhibited 29 sequence types (ST) throughout different regions in Sichuan, with 25 of these ST types being newly identified. Notably, the ST251 emerged as the predominant sequence type responsible for the pandemic. The resistance rate of isolated strains to roxithromycin was as high as 98.3%, followed by co-trimoxazole (87.5%), sulfafurazole (87.5%), imipenem (80%), amoxicillin (60%), and clindamycin (57.8%). Fifteen strains of A. hydrophila exhibited resistance to medicines across a minimum of three categories, suggesting the development of multidrug resistance in these isolates. A total of 63 ARGs were detected from the isolates, which mediated a range of antibiotic resistance mechanisms, with deactivation and efflux potentially serving as the primary mechanisms of antibiotic resistance. This study revealed the diversity of A. hydrophila genotypes and the risk of antibiotic resistance in Sichuan, providing reference for scientific and effective control of A. hydrophila infection.
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Aeromonas hydrophila , Aeromonas , Aeromonas hydrophila/genética , Tipificación de Secuencias Multilocus , Farmacorresistencia Microbiana , Genotipo , Fenotipo , Antibacterianos/farmacología , China , Aeromonas/genéticaRESUMEN
Interleukin-10 (IL-10) is a pleiotropic cytokine with both immune enhancement and immunosuppression activities, but the main role is immunosuppression and anti-inflammatory ability. In order to use the immunosuppressive function of IL-10, many viruses, such as SARS-CoV-2, hepatitis B virus and EB virus, can evade the host's immune surveillance and clearance by increasing the expression of host IL-10. However, it has not been reported whether the aquatic animal infection virus can upregulate the expression of host IL-10 and the mechanisms are still unknown. Spring viremia of carp (SVC) is a fatal viral disease for many fish species and is caused by spring viremia of carp virus (SVCV). This disease has caused significant economic losses in the aquaculture industry worldwide. In this study, the expression of carp IL-10 with or without infection of SVCV in epithelioma papulosum cyprinid (EPC) cells, carp head kidney (cHK) primary cells and common carp tissues were analyzed using RT-PCR and ELISA. The results show that SVCV infection induced carp IL-10 mRNA and protein expression, both in vitro and in vivo. However, the upregulation of carp IL-10 by SVCV was hindered by specific inhibitors of the JAK inhibitor (CP-690550), STAT3 inhibitor (STA-21), NF-κB inhibitor (BAY11-7082) and p38 MAPK (mitogen-activated protein kinase) inhibitor (SB202190), but not JNK inhibitor (SP600125). Furthermore, the results demonstrated that JAK1, JAK2, JAK3, TYK2 and STAT5 played important roles in carp IL-10 production induced by SVCV infection. Taken together, SVCV infection significantly induced carp IL-10 expression and the upregulation trigged in JAK-STAT, NF-κB and p38MAPK pathways. To our knowledge, this is the first time that a fish infection virus upregulated the host IL-10 expression through the JAK-STAT, NF-κB and p38MAPK pathways. Altogether, fish viruses may have a similar mechanism as human or other mammalian viruses to escape host immune surveillance and clearance.
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Eucommia ulmoides Oliver (EuO) is a natural medicine that can improve the composition of intestinal flora in fish, but more experiments and data are needed to support whether it can effectively improve the changes of intestinal flora and intestinal damage caused by high starch. This study examined the changes in intestinal structure as well as intestinal flora before and after the addition of EuO to high-starch diets and analyzed the effects of such changes on immune and digestive functions. The results showed that EuO reduces mortality during Nocardia seriolae attack and can reduce starch-induced intestinal inflammation. Eucommia ulmoides Oliver supplementation was able to alter the changes of intestinal flora in fatty acid degradation, bacterial chemotaxis, porphyrin metabolism and flagella assembly caused by high starch. By analyzing the abundance and correlation of bacterial communities, three bacterial communities that were significantly related to the intervention effect of EuO were screened. Further analysis revealed that EuO supplementation reduced the increase in abundance of Limnochordaceae, Nitrolancea, Lysinibacillus, and Hydrogenispora induced by high starch, which were negatively correlated with levels of the immunoreactive substance LZM in fish. This study reveals the regulatory effects of EuO on the intestinal flora of Micropterus salmoides fed on high starch diets, and provides a theoretical basis for reducing starch damage to fish in production.
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BACKGROUND: The hepatopancreas of crustaceans serves as a significant organ for both the synthesis and secretion of digestive enzymes, as well as energy storage. In the event of food shortage, the hepatopancreas can provide energy for survival. To investigate the potential regulatory mechanisms of the hepatopancreas in response to starvation in Eriocheir Sinensis, transcriptome analysis, histological study and qRT-PCR were performed. RESULTS: The results showed that starvation caused a decrease in the hepatopancreas index of E. sinensis, which had certain effects on the tissue structure, metabolism and angiogenesis in the hepatopancreas. In addition, WGCNA and linear regression analysis showed that the genes significantly related to the hepatopancreas index were mainly enriched in the angiogenesis pathway, in which AKT signaling played an important role. Starvation may inhibit AKT signaling pathway by reducing the expression of TGFBI, HSP27, HHEX, and EsPVF1, thereby hindering angiogenesis, promoting apoptosis, and leading to hepatopancreas atrophy. CONCLUSION: These results indicate that AKT plays an important role in the angiogenesis pathway and apoptosis of the starvation induced hepatopancreas index reduction, which is beneficial to further understand the effect of starvation stress on hepatopancreas of Chinese mitten crab.
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Braquiuros , Hepatopáncreas , Animales , Hepatopáncreas/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Perfilación de la Expresión Génica , Braquiuros/genéticaRESUMEN
Elizabethkingia miricola is an emerging opportunistic pathogen that is highly pathogenic in both immunocompromised humans and animals. Once the disease occurs, treatment can be very difficult. Therefore, a deep understanding of the pathological mechanism of Elizabethkingia miricola is the key to the prevention and control of the disease. In this study, we isolated the pathogenic bacteria from bullfrogs with dark skin color, weak limbs, wryneck, and cataracts. Via subsequent morphological observations and a 16S rRNA gene sequence analysis, the pathogen was identified as Elizabethkingia miricola. The histopathological and transmission electron microscopy analysis revealed that the brain was the main target organ. Therefore, brain samples from diseased and healthy bullfrogs were used for the RNA-Seq analysis. The comparative transcriptome analysis revealed that the diseased bullfrog brain was characterized by the immune activation and inflammatory response, which were mediated by the "NOD-like receptor signaling pathway" and the "Toll-like receptor signaling pathway". We also performed qRT-PCR to examine the expression profile of inflammation-related genes, which further verified the reliability of our transcriptome data. Based on the above results, it was concluded that the NOD/Toll-like receptor-related networks that dominate the immune activation and inflammatory response were activated in the brain of Elizabethkingia miricola-infected bullfrogs. This study contributes to the search for therapeutic targets for bullfrog meningitis and provides basic information for establishing effective measures to prevent and control bullfrog meningitis.
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Infecciones por Flavobacteriaceae , Flavobacteriaceae , Meningitis , Animales , Humanos , Rana catesbeiana , ARN Ribosómico 16S/genética , Reproducibilidad de los Resultados , Infecciones por Flavobacteriaceae/microbiología , Infecciones por Flavobacteriaceae/patología , Ranidae , Transducción de SeñalRESUMEN
Copper (Cu) is one of the essential trace elements in the body, but excessive amounts of Cu harm multiple organs and tissues such as liver, kidneys, testis, ovaries, and brain. However, the mechanism of hypothalamic neurotoxicity induced by Cu is still unknown. This study examined the relationship between reactive oxygen species (ROS) and mitophagy in mouse hypothalamus treated with high Cu. The results demonstrated that high levels of copper sulfate (CuSO4) could cause histopathological and neuronal changes in the mouse hypothalamus, produce a large amount of ROS, induce mitophagy, and lead to an imbalance of mitochondrial fusion/fission. The main manifestations are an increase in the expression levels of LC3-II/LC3-I, p62, DRP1, and FIS1, and a decrease in the expression levels of MFN1 and MFN2. Cu can induce mitophagy also was confirmed by LC3 co-localization with TOMM20 (mitochondrial marker). Next, the effect of oxidative stress on CuSO4-induced mitophagy was demonstrated. The results showed that ROS inhibitor N-acetylcysteine (NAC) diminished CuSO4-induced mitophagy and reversed the disturbance of mitochondrial dynamics. Additionally, a study was carried out to evaluate the role of mitophagy in CuSO4-induced hypothalamic injury. The inhibition of mitophagy using mitophagy inhibitor (Mdivi-1) decreased cell viability and promoted CuSO4-inhibited mitochondrial fusion. The aforementioned results suggested that CuSO4 induced mitophagy via oxidative stress in N38 cells and mouse hypothalamus, and that the activation of mitophagy might generate protective mechanisms by alleviating Cu-induced mitochondrial dynamics disorder. This study provided a novel approach and theoretical basis for studying and preventing Cu neurotoxicity.
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Enfermedades Mitocondriales , Mitofagia , Masculino , Ratones , Animales , Cobre/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Neuronas/metabolismoRESUMEN
Based on their good physiological functions and physical properties, carbohydrates are widely used in fish feed. However, excessive use of carbohydrates such as starch in fish feed may reduce the immunity of the fish and cause a series of health problems. In order to more clearly clarify the effects of different starch levels in feed on the immune organs of Micropterus salmoides, this study took the immune organs as the entry point and explored it from several perspectives, including differences in enzyme activity in plasma, changes in gene expression in immune organs, and resistance to pathogenic bacteria. The results showed that (1) high starch feed activates inflammatory responses in the spleen and head kidney through the MAPK signaling pathway. This leads to a decrease in the number of lymphocytes and weakens the resistance to pathogens; (2) high starch diet affects the antioxidant capacity of the trunk kidney by regulating the Keap1/Nrf2 pathway; (3) There was a strong correlation between gene expression patterns in the head kidney and lysozyme content in plasma. This implies that the high starch diet may regulate lysozyme production by affecting gene expression in the head kidney and further affect immune function. This study helps to reveal the interaction between starch and the immune system and provide scientific basis for the development of reasonable dietary recommendations and disease prevention.