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Integrative and conjugative elements (ICEs) play a vital role in bacterial evolution by carrying essential genes that confer adaptive functions to the host. Despite their importance, the mechanism underlying the stable inheritance of ICEs, which is necessary for the acquisition of new traits in bacteria, remains poorly understood. Here, we identified SezAT, a type II toxin-antitoxin (TA) system, and AbiE, a type IV TA system encoded within the ICESsuHN105, coordinately promote ICE stabilization and mediate multidrug resistance in Streptococcus suis. Deletion of SezAT or AbiE did not affect the strain's antibiotic susceptibility, but their duple deletion increased susceptibility, mainly mediated by the antitoxins SezA and AbiEi. Further studies have revealed that SezA and AbiEi affect the genetic stability of ICESsuHN105 by moderating the excision and extrachromosomal copy number, consequently affecting the antibiotic resistance conferred by ICE. The DNA-binding proteins AbiEi and SezA, which bind palindromic sequences in the promoter, coordinately modulate ICE excision and extracellular copy number by binding to sequences in the origin-of-transfer (oriT) and the attL sites, respectively. Furthermore, AbiEi negatively regulates the transcription of SezAT by binding directly to its promoter, optimizing the coordinate network of SezAT and AbiE in maintaining ICESsuHN105 stability. Importantly, SezAT and AbiE are widespread and conserved in ICEs harbouring diverse drug-resistance genes, and their coordinated effects in promoting ICE stability and mediating drug resistance may be broadly applicable to other ICEs. Altogether, our study uncovers the TA system's role in maintaining the genetic stability of ICE and offers potential targets for overcoming the dissemination and evolution of drug resistance.
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Proteínas Bacterianas , Streptococcus suis , Sistemas Toxina-Antitoxina , Streptococcus suis/genética , Streptococcus suis/efectos de los fármacos , Sistemas Toxina-Antitoxina/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Farmacorresistencia Bacteriana Múltiple/genética , Infecciones Estreptocócicas/microbiología , Infecciones Estreptocócicas/genética , Antibacterianos/farmacología , Conjugación Genética , Animales , Secuencias Repetitivas EsparcidasRESUMEN
Fungi compose a minority but a common component of normal oral microbiota and contribute to oral and systemic health by interacting with bacterial inhabitants. This study investigated the relationship of oral fungal profiles to health status and bacterial profiles of 159 elderly adults receiving community support and home care services. Fungal and bacterial densities and compositions were determined based on the fungal ribosomal internal transcribed spacer region and bacterial 16S rRNA gene amplicon analyses, respectively. The total fungal density of 87 individuals exceeded 5,000 copies, and their microbiota was characterized by significantly less dense bacterial populations and lower relative abundances of oral health-associated taxa, such as Neisseria perflava and Porphyromonas pasteri, compared with those with less than 5,000 copies of fungi. These individuals were significantly older, had fewer teeth, had lower physical function, and comprised more denture users and individuals with cognitive decline. Fungal compositions were classified into three profiles (Candida albicans-dominant, non-albicans Candida-dominant, and non-Candida-dominant), and individuals with a non-albicans Candida-dominant profile exhibited significantly lower physical and cognitive function than those with the Candida albicans-dominant profile. These results demonstrate that a high-density fungal population co-occurs with poor oral and systemic health status of the host and dysbiosis of the bacterial community, and particularly, the overgrowth of non-albicans Candida species may be implicated in worsening systemic conditions. IMPORTANCE: The interaction between fungal and bacterial components involved in the virulence of oral microbiota has received attention. This study demonstrates that an increase in fungal components is associated with a dysbiotic bacterial community and poor health status in elderly adults. Among individuals with a high-density fungal population, particularly, those with a non-albicans Candida-dominant profile had lower physical and cognitive functions than those with a C. albicans-dominant profile. These findings indicate that the evaluation of fungal components, in addition to the bacterial components, is important to understand the involvement of oral microbiota in oral and systemic diseases in elderly adults.
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Bacterias , Hongos , Estado de Salud , Servicios de Atención de Salud a Domicilio , Microbiota , Boca , Humanos , Anciano , Femenino , Masculino , Anciano de 80 o más Años , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Hongos/genética , Hongos/clasificación , Hongos/aislamiento & purificación , Boca/microbiología , ARN Ribosómico 16S/genética , Salud BucalRESUMEN
Porcine deltacoronavirus (PDCoV), a novel enteropathogenic coronavirus, causes diarrhea mainly in suckling piglets and has the potential to infect humans. Whereas, there is no commercially available vaccine which can effectively prevent this disease. In this study, to ascertain the duration of immune protection of inactivated PDCoV vaccine, suckling piglets were injected subcutaneously with inactivated PDCoV vaccine using a prime/boost strategy at 3 and 17-day-old. Neutralizing antibody assay showed that the level of the inactivated PDCoV group was still ≥1:64 at three months after prime vaccination. The three-month-old pigs were orally challenged with PDCoV strain CZ2020. Two pigs in challenge control group showed mild to severe diarrhea at 10-11 day-post-challenge (DPC), while the inactivated PDCoV group had no diarrhea. High levels of viral shedding, substantial intestinal villus atrophy, and positive straining of viral antigens in ileum were detected in challenge control group, while the pigs in inactivated PDCoV group exhibited significantly reduced viral load, minor intestinal villi damage and negative straining of viral antigens. These results demonstrated that PDCoV was pathogenic against three-month-old pigs and inactivated PDCoV vaccine can provide effective protection in pigs lasting for three months.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Infecciones por Coronavirus , Diarrea , Enfermedades de los Porcinos , Vacunas de Productos Inactivados , Vacunas Virales , Esparcimiento de Virus , Animales , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/administración & dosificación , Porcinos , Enfermedades de los Porcinos/prevención & control , Enfermedades de los Porcinos/inmunología , Enfermedades de los Porcinos/virología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Vacunas Virales/inmunología , Vacunas Virales/administración & dosificación , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/veterinaria , Diarrea/prevención & control , Diarrea/inmunología , Diarrea/virología , Vacunación , Coronavirus/inmunología , Carga Viral , Antígenos Virales/inmunologíaRESUMEN
Cotinine, the primary metabolite of nicotine in the human body, is an emerging pollutant in aquatic environments. It causes environmental problems and is harmful to the health of humans and other mammals; however, the mechanisms of its biodegradation have been elucidated incompletely. In this study, a novel Gram-negative strain that could degrade and utilize cotinine as a sole carbon source was isolated from municipal wastewater samples, and its cotinine degradation characteristics and kinetics were determined. Pseudomonas sp. JH-2 was able to degrade 100 mg/L (0.56 mM) of cotinine with high efficiency within 5 days at 30 â, pH 7.0, and 1% NaCl. Two intermediates, 6-hydroxycotinine and 6-hydroxy-3-succinoylpyridine (HSP), were identified by high-performance liquid chromatography and liquid chromatograph mass spectrometer. The draft whole genome sequence of strain JH-2 was obtained and analyzed to determine genomic structure and function. No homologs of proteins predicted in Nocardioides sp. JQ2195 and reported in nicotine degradation Pyrrolidine pathway were found in strain JH-2, suggesting new enzymes that responsible for cotinine catabolism. These findings provide meaningful insights into the biodegradation of cotinine by Gram-negative bacteria.
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Biodegradación Ambiental , Cotinina , Pseudomonas , Aguas Residuales , Pseudomonas/metabolismo , Pseudomonas/genética , Pseudomonas/aislamiento & purificación , Pseudomonas/clasificación , Cotinina/metabolismo , Cotinina/análogos & derivados , Aguas Residuales/microbiología , Nicotina/metabolismo , Nicotina/análogos & derivados , Piridinas/metabolismo , Genoma Bacteriano , Filogenia , SuccinatosRESUMEN
Klebsiella pneumoniae has become one of the most intractable gram-negative pathogens infecting humans and animals due to its severe antibiotic resistance. Bacteriophages and protein products derived from them are receiving increasing amounts of attention as potential alternatives to antibiotics. In this study, we isolated and investigated the characteristics of a new lytic phage, P1011, which lyses K5 K. pneumoniae specifically among 26 serotypes. The K5-specific capsular polysaccharide-degrading depolymerase dep1011 was identified and expressed. By establishing murine infection models using bovine strain B16 (capable of supporting phage proliferation) and human strain KP181 (incapable of sustaining phage expansion), we explored the safety and efficacy of phage and dep1011 treatments against K5 K. pneumoniae. Phage P1011 resulted in a 60% survival rate of the mice challenged with K. pneumoniae supporting phage multiplication, concurrently lowering the bacterial burden in their blood, liver, and lungs. Unexpectedly, even when confronted with bacteria impervious to phage multiplication, phage therapy markedly decreased the number of viable organisms. The protective efficacy of the depolymerase was significantly better than that of the phage. The depolymerase achieved 100% survival in both treatment groups regardless of phage propagation compatibility. These findings indicated that P1011 and dep1011 might be used as potential antibacterial agents to control K5 K. pneumoniae infection.
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Bacteriófagos , Infecciones por Klebsiella , Klebsiella pneumoniae , Animales , Klebsiella pneumoniae/virología , Klebsiella pneumoniae/fisiología , Ratones , Infecciones por Klebsiella/terapia , Infecciones por Klebsiella/veterinaria , Infecciones por Klebsiella/microbiología , Bacteriófagos/fisiología , Modelos Animales de Enfermedad , Terapia de Fagos , Femenino , Glicósido Hidrolasas/metabolismo , BovinosRESUMEN
Streptococcus suis (S. suis) is an important gram-positive pathogen and an emerging zoonotic pathogen that causes meningitis in swine and humans. Although several virulence factors have been characterized in S. suis, the underlying mechanisms of pathogenesis are not fully understood. In this study, we identified Zinc metalloproteinase C (ZmpC) probably as a critical virulence factor widely distributed in S. suis strains. ZmpC was identified as a critical facilitator in the development of bacterial meningitis, as evidenced by the detection of increased expression of TNF-α, IL-8, and matrix metalloprotease 9 (MMP-9). Subcellular localization analysis further revealed that ZmpC was localized to the cell wall surface and gelatin zymography analysis showed that ZmpC could cleave human MMP-9. Mice challenge demonstrated that ZmpC provided protection against S. suis CZ130302 (serotype Chz) and ZY05719 (serotype 2) infection. In conclusion, these results reveal that ZmpC plays an important role in promoting CZ130302 to cause mouse meningitis and may be a potential candidate for a S. suis CZ130302 vaccine.
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Meningitis Bacterianas , Serogrupo , Infecciones Estreptocócicas , Streptococcus suis , Enfermedades de los Porcinos , Streptococcus suis/patogenicidad , Streptococcus suis/enzimología , Animales , Infecciones Estreptocócicas/veterinaria , Infecciones Estreptocócicas/microbiología , Porcinos , Enfermedades de los Porcinos/microbiología , Ratones , Meningitis Bacterianas/veterinaria , Meningitis Bacterianas/microbiología , Femenino , Factores de Virulencia/metabolismo , Factores de Virulencia/genética , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Humanos , Metaloproteinasa 9 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Ratones Endogámicos BALB C , Metaloendopeptidasas/metabolismo , Metaloendopeptidasas/genéticaRESUMEN
Streptococcus suis is an important zoonotic pathogen, causing cytokine storms of Streptococcal toxic shock-like syndrome amongst humans after a wound infection into the bloodstream. To overcome the challenges of fever and leukocyte recruitment, invasive S. suis must deploy multiple stress responses forming a network and utilize proteases to degrade short-lived regulatory and misfolded proteins induced by adverse stresses, thereby adapting and evading host immune responses. In this study, we found that S. suis encodes multiple ATP-dependent proteases, including single-chain FtsH and double-subunit Clp protease complexes ClpAP, ClpBP, ClpCP, and ClpXP, which were activated as the fever of infected mice in vivo. The expression of genes ftsH, clpA/B/C, and clpP, but not clpX, were significantly upregulated in S. suis in response to heat stress, while were not changed notably under the treatments with several other stresses, including oxidative, acidic, and cold stimulation. FtsH and ClpP were required for S. suis survival within host blood under heat stress in vitro and in vivo. Deletion of ftsH or clpP attenuated the tolerance of S. suis to heat, oxidative and acidic stresses, and significantly impaired the bacterial survival within macrophages. Further analysis identified that repressor CtsR directly binds and controls the clpA/B/C and clpP operons and is relieved by heat stress. In summary, the deployments of multiple ATP-dependent proteases form a flexible heat stress response network that appears to allow S. suis to fine-tune the degradation or refolding of the misfolded proteins to maintain cellular homeostasis and optimal survival during infection.
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Zoonotic streptococci cause several invasive diseases with high mortality rates, especially meningitis. Numerous studies elucidated the meningitis pathogenesis of zoonotic streptococci, some specific to certain bacterial species. In contrast, others are shared among different bacterial species, involving colonization and invasion of mucosal barriers, survival in the bloodstream, breaching the blood-brain and/or blood-cerebrospinal fluid barrier to access the central nervous system, and triggering inflammation of the meninges. This review focuses on the recent advancements in comprehending the molecular and cellular events of five major zoonotic streptococci responsible for causing meningitis in humans or animals, including Streptococcus agalactiae, Streptococcus equi subspecies zooepidemicus, Streptococcus suis, Streptococcus dysgalactiae, and Streptococcus iniae. The underlying mechanism was summarized into four themes, including 1) bacterial survival in blood, 2) brain microvascular endothelial cell adhesion and invasion, 3) penetration of the blood-brain barrier, and 4) activation of the immune system and inflammatory reaction within the brain. This review may contribute to developing therapeutics to prevent or mitigate injury of streptococcal meningitis and improve risk stratification.
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The construction industry's high energy consumption and carbon emissions negatively impact the ecological environment; large-scale construction projects consume much energy and emit a significant amount of CO2 into the atmosphere. Statistics show that 30% of energy loss and 40% of solid waste in the construction industry are generated during construction. Therefore, reducing emissions during construction has significant research potential and value. Many scholars have recently studied eco-friendly building materials to facilitate the use of high-carbon emission materials like cement. Adding fibers to composite materials has become a research hotspot among these studies. Although adding fibers to composite materials has many advantages, it mainly reduces the compressive strength of the composite material. This research used the response surface methodology (RSM) to optimize the raw material ratios and thus improve the performance of plant fiber composite materials. Single-factor experiments were conducted to analyze the effects of grass size, grass content, and quicklime content on the composite materials' compressive strength, flexural strength, and water absorption. The influencing factors and levels for the response surface experiment were determined based on the results of the single-factor analysis. Using the response surface methodology (RSM), a second-order polynomial regression model was established to analyze the interaction effects of the three factors on the composite materials' compressive strength, flexural strength, and water absorption rate. The optimal ratio was determined: the optimized options for grass size, grass content, and quicklime content are 2.0 mm, 8.2 g, and 38 g, respectively. The actual values of compressive strength, flexural strength, and water absorption rate of the composite materials made according to the predicted ratio are 11.425 MPa, 2.145 MPa, and 21.89%, respectively, with a relative error of 8% between the actual and predicted values. X-ray diffraction and scanning electron microscopy were also used to reveal the factors contributing to the relatively high strength of the optimized samples.
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In the context of ecological sustainability, this study focuses on the effect of variables of pasture fibers on the thermal properties of slag bricks made from a green recyclable material. This experiment uses slag as the binder, sand as the aggregate, and pasture fiber as an additive. The experimental variables include the additive content ratio of the pasture fiber, the size of the pasture fiber, and the type of pasture fiber. Significance analysis of the experimental results of the thermal performance tests is carried out using Minitab 18.1.0 software, and the optimal ratios for the thermal performance of the composite samples are derived from the response optimizer and conformity analysis. The results of the experiment's test analysis using Minitab 18 software indicate that, with an increase in pasture fiber content, the thermal performance of the composite samples initially decreases before increasing. Additionally, the lower the thermal conductivity of the composite sample, the lower the apparent density and the higher the porosity. Incorporating pasture fibers into slag bricks, as revealed in this study, reduces the waste of pasture resources in pastoral areas and promotes the development of sustainable building materials with favorable thermal properties.
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To thoroughly understand ferroptosis's biological functions in living cells, it is crucial to investigate the polarity variations that occur during this unique Fe(II)-facilitated oxidative type of cell death. In this work, we report the development of a ratiometric probe (Po-P) to visualize the polarity changes in living cells and the inhibition effect during ferroptosis. The polarity-responsive fluorophore utilized by Po-P has a D-π-A-type structure. Based on theoretical calculations, ICT was proposed as the basis for Po-P's polarity-responsive mechanism. According to cell imaging results, Po-P had a desirable capacity for monitoring polarity fluctuations and erastin-induced ferroptosis. Furthermore, inhibition imaging revealed that dihydrolipoic acid (DHLA) could potentially prevent polarity changes that occur during erastin-induced ferroptosis, just as vitamin E (VE). We anticipate that the probe Po-P could be a valuable tool to quickly monitor polarity fluctuations and inhibition effects during ferroptosis and create new medications for treating disorders related to ferroptosis.
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Ferroptosis , Colorantes Fluorescentes , Ferroptosis/efectos de los fármacos , Colorantes Fluorescentes/química , Colorantes Fluorescentes/farmacología , Humanos , Ácido Tióctico/farmacología , Ácido Tióctico/química , Ácido Tióctico/análogos & derivados , Imagen Óptica/métodos , Piperazinas/farmacología , Piperazinas/químicaRESUMEN
This study aimed to investigate the changes in flavor quality of roasted duck during repetitive freeze-thawing (FT, -20 â for 24 h, then at 4 â for 24 h for five cycles) of raw duck preforms. HS-SPME/GC-MS analysis showed that more than thirty volatile flavor compounds identified in roasted ducks fluctuated with freeze-thawing of raw duck preforms, while hexanal, nonanal, 1-octen-3-ol, and acetone could as potential flavor markers. Compared with the unfrozen raw duck preforms (FT-0), repetitive freeze-thawing increased the protein/lipid oxidation and cross-linking of raw duck preforms by maintaining the higher carbonyl contents (1.40 â¼ 3.30 nmol/mg), 2-thiobarbituric acid reactive substances (0.25 â¼ 0.51 mg/kg), schiff bases and disulfide bond (19.65 â¼ 30.65 µmol/g), but lower total sulfhydryl (73.37 â¼ 88.94 µmol/g) and tryptophan fluorescence intensity. Moreover, A lower protein band intensity and a transformation from α-helixes to ß-sheets and random coils were observed in FT-3 â¼ FT-5. The obtained results indicated that multiple freeze-thawing (more than two cycles) of raw duck preforms could be detrimental to the flavor quality of the roasted duck due to excessive oxidation and degradation.
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Culinaria , Patos , Congelación , Cromatografía de Gases y Espectrometría de Masas , Gusto , Compuestos Orgánicos Volátiles , Animales , Compuestos Orgánicos Volátiles/análisis , Manipulación de Alimentos/métodos , Oxidación-Reducción , Calidad de los Alimentos , Sustancias Reactivas al Ácido Tiobarbitúrico/análisisRESUMEN
Variable pressure salting (VPS) is considered a novel salting approach to improve meat quality. This study aimed to investigate the effects of roasted duck's edible and nutritional quality after VPS through serum biochemical indicators and in vivo digestion properties in rats. The results show that roasted duck after VPS led to an increase in the total protein content (57.24 g/L) and blood glucose levels (6.87 mmol/L), as well as a decrease in the blood urea nitrogen content (11.81 mmol/L), in rats. Compared to rats fed base diets and roasted duck after static wet salting (SWS), those ingesting roasted duck after VPS exhibited higher values of apparent protein digestibility (51.24%), pepsin activity (2.40 U/mg), and trypsin activity (389.80 U/mg). Furthermore, VPS treatment improved the textural properties and microstructure of duck breasts shown by a higher immobilized water relaxation area and more ordered protein structures (α-helixes and ß-sheets). These improvements enhanced the protein anabolism capacity and in vivo digestion properties in rats. Therefore, VPS represents a beneficial salting method for promoting effective digestion and absorption in rats.
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The enrichment of oral taxa in the gut has recently been reported as a notable alteration in the microbial balance in patients with intestinal disorders. However, translocation in populations without such diseases remains controversial. In this study, we examined 49 pairs of tongue and rectal samples collected from orthopedic patients without a history of intestinal disorders to verify the presence of oral taxa in the rectal microbiota. The bacterial composition of each sample was determined using 16S rRNA gene sequencing and amplicon sequence variant (ASV) analysis. Although the bacterial compositions of the tongue and rectal microbiota were distinctly different, tongue ASVs were detected in 67.3% of the participants and accounted for 0.0%-9.37% of the rectal microbiota. Particularly, Streptococcus salivarius, Fusobacterium nucleatum, and Streptococcus parasanguinis were abundant in the rectal microbiota. According to the network analysis, tongue taxa, such as S. salivarius and S. parasanguinis, formed a cohabiting group with Klebsiella pneumoniae and Alistipes finegoldii in the rectal microbiota. The total abundance of tongue ASVs in the rectal microbiota was significantly higher in participants with older age, hypertension, and proton pump inhibitor (PPI) use. Our study presents an extensive translocation of oral taxa to the rectum of a population without intestinal disorders and suggests that aging, hypertension, and PPI use are associated with an increased abundance of oral taxa and potential pathogenic bacteria in the rectal microbiota.
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Bacterias , Microbioma Gastrointestinal , ARN Ribosómico 16S , Recto , Lengua , Humanos , Masculino , Femenino , ARN Ribosómico 16S/genética , Persona de Mediana Edad , Microbioma Gastrointestinal/genética , Adulto , Lengua/microbiología , Anciano , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Recto/microbiología , Boca/microbiología , ADN Bacteriano/genética , Adulto Joven , Inhibidores de la Bomba de Protones , Análisis de Secuencia de ADN , Hipertensión/microbiología , MicrobiotaRESUMEN
BACKGROUND: Baoyuan decoction (BYD) has been widely utilized as a traditional prescription for the treatment of various conditions such as coronary heart disease, aplastic anemia, and chronic renal failure. However, its potential efficacy in improving atherosclerosis has not yet been investigated. PURPOSE: Our research aimed to assess the potential of BYD as an inhibitor of atherosclerosis and uncover the underlying mechanism by which it acts on foam cell formation. STUDY DESIGN AND METHODS: High-fat diet-induced ApoE-/- mice were employed to explore the effect of BYD on atherosclerosis. The differential metabolites in feces were identified and analyzed by LC-Qtrap-MS. In addition, we utilized pharmacological inhibition of BYD on foam cell formation induced by oxLDL in THP-1 cells to elucidate the underlying mechanisms specifically in macrophages. RESULTS: The atherosclerotic plaque burden in the aortic sinus of ApoE-/- mice was notably reduced with BYD treatment, despite no significant alterations in plasma lipids. Metabolomic analysis revealed that BYD suppressed the increased levels of peroxidized fatty acids, specifically 9/13-hydroxyoctadecadienoic acid (9/13-HODE), in the feces of mice. As a prominent peroxidized fatty acid found in oxLDL, we confirmed that 9/13-HODE induced the overexpression of CD36 in THP-1 macrophages by upregulating PPARγ. In subsequent experiments, the decreased levels of CD36 triggered by oxLDL were observed after BYD treatment. This decrease occurred through the regulation of the Src/MMK4/JNK pathway, resulting in the suppression of lipid deposition in THP-1 macrophages. CONCLUSIONS: These results illustrate that BYD exhibits potential anti-atherosclerotic effects by inhibiting CD36 expression to prevent foam cell formation.
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Aterosclerosis , Antígenos CD36 , Medicamentos Herbarios Chinos , Células Espumosas , Lipoproteínas LDL , Animales , Aterosclerosis/tratamiento farmacológico , Antígenos CD36/metabolismo , Medicamentos Herbarios Chinos/farmacología , Humanos , Masculino , Ratones , Células Espumosas/efectos de los fármacos , Células Espumosas/metabolismo , Lipoproteínas LDL/metabolismo , Dieta Alta en Grasa , Ácidos Grasos , Ratones Endogámicos C57BL , Células THP-1 , Placa Aterosclerótica/tratamiento farmacológico , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Apolipoproteínas ERESUMEN
Objective: To assess the feasibility and diagnostic performances of synthetic magnetic resonance imaging (SyMRI) combined with diffusion-weighted imaging (DWI) and differential subsampling with cartesian ordering (DISCO) in breast imaging reporting and data system (BI-RADS) 4 lesions. Methods: A total of 98 BI-RADS 4 patients, including 68 cases assigned to a malignant group and 33 cases assigned to a benign group, were prospectively enrolled, and their MRI and clinical information were collected. Two physicians jointly analyzed the characteristics of conventional MRI. T1, T2, proton density (PD), and ADC values were obtained from three different regions of interest (ROIs). Logistic regression analyses were used to select features and build models, and a nomogram was constructed with the best model. Results: Using the ROI delineation method at the most obvious enhancement to measure the ADC value revealed the best diagnostic performance in diagnosing BI-RADS type 4 mass lesions. The diagnostic efficiency of the maximum level drawing method of the quantitative relaxation model was better than that of the whole drawing method and the most obvious enhancement method. The best relaxation model (model A) was composed of two parameters: T2stand and ΔT1%stand (AUC=0.887), and the BI-RADS model (model B) was constructed by two MRI features of edge and TIC curve (AUC=0.793). Using the quantitative parameters of SyMRI and DWI of the best ROC method combined with DISCO enhanced MRI features to establish a joint diagnostic model (model C: edge, TIC curve type, ADClocal, T2stand, ΔT1%stand) showed the best diagnostic efficiency (AUC=0.953). The nomogram also had calibration curves with good overlap. Conclusions: The combined diagnosis model of SyMRI and DWI quantitative parameters combined with DISCO can improve the diagnostic efficiency of BI-RADS 4 types of mass lesions. Also, the line diagram based on this model can be used as an auxiliary diagnostic tool.
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Apoptosis-enhancing nuclease (AEN), which shares close evolutionary relationships with the interferon-stimulated gene 20 protein (ISG20) homologs in humans, is a member of the DEDDh exonuclease family. Numerous studies on various pathogens have identified the essential roles of ISG20 in inhibiting virus replication. However, the fundamental functions of AEN during viral infection remain largely unknown. This study discovered that AEN expression was significantly upregulated in MARC-145 cells infected with Porcine epidemic diarrhea virus (PEDV) strain 85-7. In contrast, the amount of AEN protein decreased as viral replication increased. It was found that PEDV nsp1 and nsp5 mediated the decrease in AEN production, suggesting that an increase in AEN was not conducive to virus replication. By comparing AEN and its exonuclease-inactive mutant AEN-4A, we determined that the antiviral activity of AEN was independent of its exonuclease function. qPCR analyses revealed that AEN and AEN-4A could induce a significant increase in the transcription levels of IFN-α, IFN-ß, and ISGs (OASL, IFI44, IFIT2, ISG15, Mx1, Mx2), and that AEN-4A has a higher induction ability. Overexpression of AEN and AEN-4A in MARC-145 cells targeting IFN-ß knockdown or IFN-deficient Vero cells showed reduced or a complete loss of antiviral activity of both, suggesting that AEN may activate the type I IFN immune response and promote the expression of ISGs, thereby inhibiting PEDV replication. Taken together, our data prove the novel mechanism of AEN-mediated virus restriction.
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The escalating crisis of polyethylene terephthalate (PET) microplastic contamination in biological wastewater treatment systems is a pressing environmental concern. These microplastics inevitably accumulate in sewage sludge due to the absence of effective removal technologies. Addressing this urgent issue, this study introduces a novel approach using DuraPETase, a potent enzyme with enhanced PET hydrolytic activity at ambient temperatures. Remarkably, this enzyme was successfully secreted from Comamonas testosteroni CNB-1, a dominant species in the active sludge. The secreted DuraPETase showed significant hydrolytic activity toward p-NPB and PET nanoplastics. Furthermore, the CNB-1 derived whole-cell biocatalyst was able to depolymerize PET microplastics under ambient temperature, achieving a degradation efficiency of 9% within 7 days. The CNB-1-based whole biocatalysts were also capable of utilizing PET degradation intermediates, such as terephthalic acid (TPA) and ethylene glycol (EG), and bis(2-hydroxyethyl)-TPA (BHET), for growth. This indicates that it can completely mineralize PET, as opposed to merely breaking it down into smaller molecules. This research highlights the potential of activated sludge as a potent source for insitu microplastic removal.