RESUMO
Ralstonia pickettii, the most critical clinical pathogen of the genus Ralstonia, has been identified as a causative agent of numerous harmful infections. Additionally, Ralstonia pickettii demonstrates adaptability to extreme environmental conditions, such as those found in drinking water. In this study, we conducted a comprehensive genomic analysis to investigate the genomic characteristics related to potential pathogenicity and adaptive evolution in drinking water environments of Ralstonia pickettii. Through phylogenetic analysis and population genetic analysis, we divided Ralstonia pickettii into five Groups, two of which were associated with drinking water environments. The open pan-genome with a large and flexible gene repertoire indicated a high genetic plasticity. Significant differences in functional enrichment were observed between the core- and pan-genome of different groups. Diverse mobile genetic elements (MGEs), extensive genomic rearrangements, and horizontal gene transfer (HGT) events played a crucial role in generating genetic diversity. In drinking water environments, Ralstonia pickettii exhibited strong adaptability, and the acquisition of specific adaptive genes was potentially facilitated by genomic islands (GIs) and HGT. Furthermore, environmental pressures drove the adaptive evolution of Ralstonia pickettii, leading to the accumulation of unique mutations in key genes. These mutations may have a significant impact on various physiological functions, particularly carbon metabolism and energy metabolism. The presence of virulence-related elements associated with macromolecular secretion systems, virulence factors, and antimicrobial resistance indicated the potential pathogenicity of Ralstonia pickettii, making it capable of causing multiple nosocomial infections. This study provides comprehensive insights into the potential pathogenicity and adaptive evolution of Ralstonia pickettii in drinking water environments from a genomic perspective.
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The unsteady foaming-agent mixing ratio in traditional foam-dust-suppression technology limited the dust suppression efficiency. Recent studies proved that the steady mixing ratio could be guaranteed by keeping the jet pumps or Venturis working under cavitation conditions, but the pressure loss of the current devices was over 50%. To decrease the pressure loss under cavitation conditions, we proposed a new mixing device by introducing a spoiler in the Venturi structure. Through computational fluid dynamics (CFD) simulation, the spoiler structure influence on the downstream flow field and the cavitation cloud structure, which affected the total pressure loss of the device, were revealed. For structure optimization, the effect of the other geometric parameters, including the throat length and divergent angle, on the pressure loss was also studied. The proposed device enhanced the cavitation on the suction tube side of the throat; meanwhile, the cavitation in other parts of the device was avoided. Therefore, the cavitation zone in the proposed device was much smaller than that in current devices, and the pressure loss was reduced significantly. When the flow ratio was 0.5-1%, the critical pressure ratio of the proposed mixing device was 0.71-0.68, which indicated that the pressure loss was only 29%-32%. The laboratory experiment verified that when the proposed device worked under cavitation conditions, the accurate and steady mixing ratio was guaranteed. The field experiment indicated that due to the reduced pressure loss of the proposed device, the required water inlet pressure decreased to 0.29 MPa, and the dust suppression rate increased dramatically. This study was of important value in manipulating cavitation cloud structure using a spoiler, clarifying the influence of the cavitation cloud structure on the liquid mixing performance and expanding the application field of the cavitating mixing method.
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1. Schisandra chinensis, also called wuweizi in Chinese, is the fruit of Schisandra chinensis (Turcz.) Baill., and has been officially utilized as an astringent tonic for more than two thousand years in China. This study aims to evaluate the inhibition of carboxylesterases (CESs) by the major ingredients isolated from Schisandra chinensis, including Anwuligan, Schisandrol B, Schisanhenol, deoxyschizandrin, and Schisandrin B. 2. In vitro human liver microsomes (HLMs)-catalyzed hydrolysis of 2-(2-Benzoyl-3-methoxyphenyl) benzothiazole (BMBT) and fluorescein diacetate (FD) was employed as the probe reaction for CES1 and CES2, respectively. Initial screening, inhibition kinetics determination (inhibition type and parameters (Ki)), and in silico docking method were carried out. 3. Schisandrin B showed strong inhibition on the activity of CES1, and the activity of CES2 was strongly inhibited by Anwuligan and Schisandrin B. Schisandrin B exhibited noncompetitive inhibition towards CES1 and CES2. Anwuligan showed competitive inhibition towards CES2. The inhibition kinetic parameters (Ki) were calculated to be 29.8, 0.6, and 8.1 uM for the inhibition of Schisandrin B on CES1, Anwuligan on CES2, and Schisandrin B on CES2. In silico docking showed that hydrogen bonds and hydrophobic interactions contributed to the inhibition of Schisandrin B on CES1, Anwuligan on CES2, and Schisandrin B on CES2. All these information will be helpful for understanding the adverse effects of Schisandra chinensis due to the inhibition of CESs-catalyzed metabolism.
Assuntos
Carboxilesterase/antagonistas & inibidores , Hidrolases de Éster Carboxílico/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Schisandra/química , Carboxilesterase/química , Carboxilesterase/metabolismo , Hidrolases de Éster Carboxílico/química , Hidrolases de Éster Carboxílico/metabolismo , Ciclo-Octanos/farmacologia , Dioxóis/farmacologia , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Interações Medicamentosas , Inibidores Enzimáticos/química , Humanos , Lignanas/farmacologia , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , Simulação de Acoplamento Molecular , Compostos Policíclicos/farmacologiaRESUMO
The detection and treatment of cancer cells at an early stage are crucial for prolonging the survival time and improving the quality of life of patients. Upconversion nanoparticles (UCNPs) have unique physical and chemical advantages and likely provide a platform for detecting and treating cancer cells at an early stage. In this paper, the principle of UCNPs as chemical sensors based on fluorescence resonance energy transfer (FRET) has been briefly introduced. Research progress in such chemical sensors for detecting and analyzing bioactive substances and heavy metal ions at the subcellular level has been summarized. The principle of UCNP-based nanoprobe-targeting of cancer cells has been described. The research progress in using nanocomposites for cancer cell detection, namely cancer cell targeted imaging and tissue staining, has been discussed. In the field of cancer treatment, the principles and research progress of UCNPs in photodynamic therapy and photothermal therapy of cancer cells are systematically discussed. Finally, the prospects for UCNPs and remaining challenges to UCNP application in the field of cancer diagnosis and treatment are briefly described. This review provides powerful theoretical guidance and useful practical information for the research and application of UCNPs in the field of cancer.
Assuntos
Metais Terras Raras/química , Nanopartículas/química , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Antineoplásicos/administração & dosagem , Linhagem Celular Tumoral , Transferência Ressonante de Energia de Fluorescência/métodos , Humanos , MicroRNAs/administração & dosagem , MicroRNAs/farmacocinética , Imagem Molecular/métodos , Nanocompostos/química , Neoplasias/patologia , Fármacos Fotossensibilizantes/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/farmacocinéticaRESUMO
Endocrine disrupting chemicals may disrupt developing neuroendocrine systems, especially when the exposure occurs during a critical period. This study aimed to investigate whether prenatal exposure to di-(2-ethylhexyl) phthalate (DEHP), a major component of plasticizers used worldwide, disrupted the development of a network of genes important for neuroendocrine function in male rats. Pregnant rats were treated with corn oil (vehicle control), 2, 10 or 50 mg/kg DEHP by gavage from gestational day 14 to 19. The neuroendocrine gene expressions were quantified using a 48-gene Taqman qPCR array in the whole hypothalamus of neonatal rats (postnatal day 1) and in the anteroventral periventricular nucleus (AVPV), medial preoptic nucleus (MPN) and arcuate nucleus (ARC) of adult rats (postnatal day 70). Immunofluorescent signals of ERα and CYP19 were detected using the confocal microscopy in adult AVPV, MPN and ARC. The results showed that prenatal DEHP exposure perturbed somatic and reproductive development of offspring. Eleven genes were down-regulated in neonatal hypothalamus and showed non-monotonic dose-response relationships, that the 10 mg/kg DEHP dosage was associated with the greatest number of gene expression changes. Different from this, 14 genes were altered in adult AVPV, MPN and ARC and most of alterations were found in the 50 mg/kg DEHP group. Also, 50 mg/kg DEHP reduced ERα expression in the ARC, but no alterations were observed in CYP19 expression. These results indicated that prenatal DEHP exposure may perturb hypothalamic gene programming and the influences are permanent. The effects showed dependence on developmental stages and nuclei region.