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Objective: To investigate the occurrence and influencing factors of oral frailty in elderly residents of elderly care facilities and to provide a basis for the development of effective intervention programs for oral frailty in this population. Methods: A combination of subjective and objective measurements of oral frailty, a general information questionnaire, a leisure activity questionnaire, the Dietary Variety Score (DVS), the Short Nutritional Assessment Questionnaire (SNAQ), the Short-Form Mini Nutritional Assessment (MNA-SF), Barthel Index (BI), the Mini-Mental State Examination (MMSE), 15-Item Geriatric Depression Scale (GDS-15), and the Generalized Anxiety Disorder Scale-2 (GAD-2) were used to survey 348 elderly residents in three elderly care facilities in Chengdu and to analyze the factors related to oral frailty. Results: The prevalence of oral frailty in elderly residents of elderly care facilities was 31.0% (108/348). Multivariate logistic regression analysis revealed that advanced age (odds ratio [OR]=1.347, 95% confidence interval [CI]: 1.237-1.496, P<0.001), cognitive impairment (OR=6.769, 95% CI: 2.628-18.916, P<0.001), and depression (OR=8.632, 95% CI: 1.931-44.387, P=0.007) were risk factors for oral frailty in elderly residents of elderly care facilities. High scores in leisure activities (OR=0.883, 95% CI: 0.786-0.986, P=0.030), and dietary diversity (OR=0.199, 95% CI: 0.069-0.530, P=0.002) were protective factors against oral frailty. Conclusion: The prevalence of oral frailty is relatively high among elderly residents of elderly care facilities. Risk factors for oral frailty include advanced age, cognitive impairment, and depression, while increased levels of leisure activities and dietary diversity can help prevent the occurrence of oral frailty in elderly individuals.
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Anciano Frágil , Fragilidad , Humanos , Anciano , Fragilidad/epidemiología , Anciano Frágil/estadística & datos numéricos , Anciano de 80 o más Años , Encuestas y Cuestionarios , Hogares para Ancianos/estadística & datos numéricos , Masculino , Evaluación Geriátrica , Femenino , Prevalencia , Factores de Riesgo , Depresión/epidemiología , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/etiología , China/epidemiología , Evaluación NutricionalRESUMEN
Monascus pigments (MPs), a class of secondary metabolites produced by Monascus spp., can be classified into yellow, orange, and red MPs according to their differences in the wavelength of the maximum absorption. However, the biosynthetic sequence and cellular biosynthesis mechanism of different MPs components are still not yet completely clear in Monascus spp. In this study, the subcellular localization of five MPs synthases was investigated using fluorescent protein fusion expression. The results revealed that the proteins encoded by the MPs biosynthetic gene cluster were compartmentalized in various subcellular locations, including the mitochondrial polyketide synthase MrPigA, cytosolic enzymes consisting of the ketoreductase MrPigC, the oxidoreductase MrPigE, and the monooxygenase MrPigN, and the cell-wall-bound oxidoreductase MrPigF. Moreover, the correct localization of MrPigF to the cell wall was crucial for the synthesis of orange MPs. Lastly, we discussed the compartmentalized biosynthetic pathway of MPs. This study will not only be helpful in clarifying the biosynthetic sequence and biosynthesis mechanism of different MPs but also provides new insights into the cellular biosynthesis of secondary metabolites in filamentous fungi.
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Gold nanoclusters (Au NCs) with bright emission and unique chemical reactivity characters have been widely applied for optical sensing and imaging. With a combination of surface modifications, effective therapeutic treatments of tumors are realized. In this review, we summarize the recently adopted biosensing and therapy events based on Au NCs. Homogeneous and fluorometric biosensing systems toward various targets, including ions, small molecules, reactive oxygen species, biomacromolecules, cancer cells, and bacteria, in vitro and in vivo, are presented by turn-off, turn-on, and ratiometric tactics. The therapy applications are concluded in three aspects: photodynamic therapy, photothermal therapy, and as a drug carrier. The basic mechanisms and performances of these systems are introduced. Finally, this review highlights the challenges and future trend of Au NC-based biosensing and therapy systems.
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Fotoquimioterapia , Portadores de Fármacos , Fluorometría , Oro/uso terapéutico , Terapia FototérmicaRESUMEN
Antimicrobial resistance (AMR) in clinically priority pathogensis now a major threat to public health worldwide. Phages are bacterial parasites that efficiently infect or kill specific strains and represent the most abundant biological entities on earth, showing great attraction as potential antibacterial therapeutics in combating AMR. This review provides a summary of phage-inspired strategies to combat AMR. We firstly cover the phage diversity, and then explain the biological principles of phage therapy that support the use of phages in the post-antimicrobial era. Furthermore, we state the versatility methods of phage therapy both from direct access as well as collateral access. Among the direct access approaches, we discuss the use of phage cocktail therapy, phage-encoded endolysins and the bioengineering for function improvement of used phages or endolysins. On the other hand, we introduce the collateral access, including the phages antimicrobial immunity combined therapy and phage-based novel antibacterial mimic molecules. Nowadays, more and more talented and enthusiastic scientist, doctors, pharmacists, media, authorities, and industry are promoting the progress of phage therapy, and proposed more phages-inspired strategy to make them more tractable to combat AMR and benefit more people, more animal and diverse environment in "one health" framework.
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Bacteriófagos , Animales , Humanos , Bacterias/genética , Farmacorresistencia Bacteriana , Antibacterianos/farmacología , Antibacterianos/uso terapéuticoRESUMEN
BACKGROUND: Oral squamous cell carcinoma (OSCC), the predominant malignancy of the oral cavity, is characterized by high incidence and low survival rates. Emerging evidence suggests a link between circadian rhythm disruptions and cancer development. The circadian gene TIMELESS, known for its specific expression in various tumors, has not been extensively studied in the context of OSCC. This study aims to explore the influence of TIMELESS on OSCC, focusing on cell growth and metabolic alterations. METHODS: We analyzed TIMELESS expression in OSCC using western blot, immunohistochemistry, qRT-PCR, and data from The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE). The role of TIMELESS in OSCC was examined through clone formation, MTS, cell cycle, and EdU assays, alongside subcutaneous tumor growth experiments in nude mice. We also assessed the metabolic impact of TIMELESS by measuring glucose uptake, lactate production, oxygen consumption, and medium pH, and investigated its effect on key metabolic proteins including silent information regulator 1 (SIRT1), hexokinase 2 (HK2), pyruvate kinase isozyme type M2 (PKM2), recombinant lactate dehydrogenase A (LDHA) and glucose transporter-1 (GLUT1). RESULTS: Elevated TIMELESS expression in OSCC tissues and cell lines was observed, correlating with reduced patient survival. TIMELESS overexpression enhanced OSCC cell proliferation, increased glycolytic activity (glucose uptake and lactate production), and suppressed oxidative phosphorylation (evidenced by reduced oxygen consumption and altered pH levels). Conversely, TIMELESS knockdown inhibited these cellular and metabolic processes, an effect mirrored by manipulating SIRT1 levels. Additionally, SIRT1 was positively associated with TIMELESS expression. The expression of SIRT1, HK2, PKM2, LDHA and GLUT1 increased with the overexpression of TIMELESS levels and decreased with the knockdown of TIMELESS. CONCLUSION: TIMELESS exacerbates OSCC progression by modulating cellular proliferation and metabolic pathways, specifically by enhancing glycolysis and reducing oxidative phosphorylation, largely mediated through the SIRT1 pathway. This highlights TIMELESS as a potential target for OSCC therapeutic strategies.
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Péptidos y Proteínas de Señalización del Ritmo Circadiano , Glucosa , Neoplasias de la Boca , Carcinoma de Células Escamosas de Cabeza y Cuello , Animales , Humanos , Ratones , Línea Celular Tumoral , Proliferación Celular/genética , Glucosa/metabolismo , Transportador de Glucosa de Tipo 1 , Lactatos , Ratones Desnudos , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Sirtuina 1/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Péptidos y Proteínas de Señalización del Ritmo Circadiano/genéticaRESUMEN
BACKGROUND: The objective of this study is to investigate and understand the characteristics of odontogenic brain abscess. METHODS: A case of brain abscess suspected to be caused by odontogenic infection was documented, and a comprehensive analysis and summary of odontogenic brain abscess cases reported in various countries over the past 20 years was conducted. RESULTS: Based on the analysis and synthesis of both the present and previous reports, we have examined and consolidated the distinctive features of odontogenic brain abscess, the potential transmission pathway of pathogenic bacteria, diagnostic assertions, verification techniques, and crucial considerations during treatment. CONCLUSION: This investigation contributes to an enhanced comprehension and improved clinical identification of odontogenic brain abscess.
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Absceso Encefálico , Enfermedades Dentales , Humanos , Absceso Encefálico/microbiología , Enfermedades Dentales/complicacionesRESUMEN
Antibiotic-resistant bacteria are current threats to available antibiotic therapies, and this has renewed interest in the therapeutic use of phage as an alternative. However, development of phage resistance has led to unsuccessful therapeutic outcomes. In the current study, we applied phage training to minimize bacterial phage resistance and to improve treatment outcome by adapting the phage to their target hosts during co-evolution. We isolated and characterized a novel Pseudomonas aeruginosa N4-like lytic phage (PWJ) from wastewater in Yangzhou, China. PWJ is a double-stranded DNA podovirus that can efficiently lyse the model strain ATCC 27,853 and opportunistic pathogen PAO1. Genome sequencing of PWJ revealed features similar to those of the N4-like P. aeruginosa phage YH6. We used PWJ to screen for an evolved trained phage (WJ_Ev14) that restored infectivity to PWJ phage bacterial resisters. BLASTN analysis revealed that WJ_Ev14 is identical to its ancestor PWJ except for the amino acid substitution R1051S in its tail fiber protein. Moreover, phage adsorption tests and transmission electron microscopy of resistant bacteria demonstrated that the R1051S substitution was most likely the reason WJ_Ev14 could re-adsorb and regain infectivity. Furthermore, phage therapy assays in vitro and in a mouse P. aeruginosa lung infection model demonstrated that PWJ treatment resulted in improved clinical results and a reduction in lung bacterial load whereas the joint phage cocktail (PWJ+ WJ_Ev14) was better able to delay the emergence of resister bacteria. The phage cocktail (PWJ +WJ_Ev14) represents a promising candidate for inclusion in phage cocktails developed for clinical applications.
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Effective and precise mammalian transcriptome engineering technologies are needed to accelerate biological discovery and RNA therapeutics. Despite the promise of programmable CRISPR-Cas13 ribonucleases, their utility has been hampered by an incomplete understanding of guide RNA design rules and cellular toxicity resulting from off-target or collateral RNA cleavage. Here, we quantified the performance of over 127,000 RfxCas13d (CasRx) guide RNAs and systematically evaluated seven machine learning models to build a guide efficiency prediction algorithm orthogonally validated across multiple human cell types. Deep learning model interpretation revealed preferred sequence motifs and secondary features for highly efficient guides. We next identified and screened 46 novel Cas13d orthologs, finding that DjCas13d achieves low cellular toxicity and high specificity-even when targeting abundant transcripts in sensitive cell types, including stem cells and neurons. Our Cas13d guide efficiency model was successfully generalized to DjCas13d, illustrating the power of combining machine learning with ortholog discovery to advance RNA targeting in human cells.
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Sistemas CRISPR-Cas , Aprendizaje Profundo , ARN , Humanos , Sistemas CRISPR-Cas/genética , ARN/genética , ARN Guía de Sistemas CRISPR-Cas , TranscriptomaRESUMEN
Spores are important as dispersal and survival propagules in fungi. In this study we investigated the variation in number, shape, size and germination mode of ascospores in Morchella galilaea, the only species of the genus Morchella known to fruit in the autumn. Based on the observation of five samples, we first discovered significant variation in the shape and size of ascospores in Morchella. One to sixteen ascospores were found in the asci. Ascospore size correlated negatively with ascospore number, but positively with ascus size, and ascus size was positively correlated with ascospore number. We noted that ascospores, both from fresh collections and dried specimens, germinated terminally or laterally either by extended germ tubes, or via the production of conidia that were formed directly from ascospores at one, two or multiple sites. The direct formation of conidia from ascospores takes place within asci or after ascospores are discharged. Using laser confocal microscopy, we recorded the number of nuclei in ascospores and in conidia produced from ascospores. In most ascospores of M. galilaea, several nuclei were observed, as is typical of species of Morchella. However, nuclear number varied from zero to around 20 in this species, and larger ascospores harbored more nuclei. One to six nuclei were present in the conidia. Nuclear migration from ascospores to conidia was observed. Conidia forming directly from ascospores has been observed in few species of Pezizomycetes; this is the first report of the phenomenon in Morchella species. Morphological and molecular data show that conidial formation from ascospores is not found in all the specimens of this species and, hence, is not an informative taxonomic character in M. galilaea. Our data suggest that conidia produced from ascospores and successive mitosis within the ascus may contribute to asci with more than eight spores. The absence of mitosis and/or nuclear degeneration, as well as cytokinesis defect, likely results in asci with fewer than eight ascospores. This study provides new insights into the poorly understood life cycle of Morchella species and more broadly improves knowledge of conidia formation and reproductive strategies in Pezizomycetes.
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Primary extraosseous plasmacytoma (PEP) is a rare and localized form of plasmacytoma that is not well understood. This study aimed to investigate the clinical features and prognostic factors associated with PEP. Using the Surveillance, Epidemiology, and End Results (SEER) database, a total of 1044 patients diagnosed with PEP between 2000 and 2019 were identified. The average age was 60.3 ± 15.2 years, with 64.3% being male (male: female = 1.8:1) and 53.8% being over 60-year old. The survival outcome of patients with PEP depends on several factors including age, race, marital status, and treatment options such as chemotherapy, radiotherapy, and surgery, which were also identified as independent predictors of overall survival for PEP. Patients who were younger, Asian or Pacific Islander, American Indian or Native American, and received radiotherapy or surgery had a more favorable prognosis, while those who underwent chemotherapy had poorer outcomes.
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Plasmacitoma , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Plasmacitoma/diagnóstico , Plasmacitoma/epidemiología , Plasmacitoma/terapia , Estudios de Seguimiento , Programa de VERF , PronósticoRESUMEN
Coconut water (CW) is a popular and healthful beverage, and ensuring its quality is crucial for consumer satisfaction. This study aimed to explore the potential of near-infrared spectroscopy (NIRS) and chemometric methods for analyzing CW quality and distinguishing samples based on postharvest storage time, cultivar, and maturity. CW from nuts of Wenye No. 2 and Wenye No. 4 cultivars in China, with varying postharvest storage time and maturities, were subjected to NIRS analysis. Partial least squares regression (PLSR) models were developed to predict reducing sugar and soluble sugar contents, revealing moderate applicability but lacking accuracy, with the residual prediction deviation (RPD) values ranging from 1.54 to 1.83. Models for TSS, pH, and TSS/pH exhibited poor performance with RPD values below 1.4, indicating limited predictability. However, the study achieved a total correct classification rate exceeding 95% through orthogonal partial least squares discriminant analysis (OPLS-DA) models, effectively discriminating CW samples based on postharvest storage time, cultivar, and maturity. These findings highlight the potential of NIRS combined with appropriate chemometric methods as a valuable tool for analyzing CW quality and efficiently distinguishing samples. NIRS and chemometric techniques enhance quality control in coconut water, ensuring consumer satisfaction and product integrity.
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Granular materials are critical to many natural and industrial processes, yet the chaotic flow behavior makes granular dynamics difficult to understand, model, and control, causing difficulties for natural disaster mitigation as well as scale-up and optimization of industrial devices. Hydrodynamic instabilities in externally excited grains often resemble those in fluids, but have different underlying mechanisms, and these instabilities provide a pathway to understand geological flow patterns and control granular flows in industry. Granular particles subject to vibration have been shown to exhibit Faraday waves analogous to those in fluids; however, waves can only form at high vibration strengths and in shallow layers. Here, we demonstrate that combined gas flow and vibration induces granular waves without these limitations to enable structured, controllable granular flows at larger scale with lower energy consumption for potential industrial processes. Continuum simulations reveal that drag force under gas flow creates more coordinated particle motions to allow waves in taller layers as seen in liquids, bridging the gap between waves produced in conventional fluids and granular particles subject to vibration alone.
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Heat shock proteins (HSPs) play critical roles in regulating different mechanisms under high-temperature conditions. HSPs have been identified and well-studied in different plants. However, there is a lack of information about their genomic organization and roles in medicinal plants and fungi, especially in Wolfi-poria cocos (W. cocos). We identified sixteen heat shock proteins (HSPs) in W. cocos and analyzed in terms of phylogenetic analysis, gene structure, motif distribution patterns, physiochemical properties, and expression comparison in different strains. Based on phylogenetic analysis, HSPs were divided into five subgroups (WcHSP100, WcHSP90, WcHSP70, WcHSP60, and WcsHSP). Subgroups WcHSP100s, WcHSP90s, WcHSP70s, WcHSP60, and WcsHSPs were further divided into 3, 2, 3, 1, and 6 subfamilies, respectively. Moreover, the expression profiling of all HSP genes in five strains of W. cocos under different temperature extremes revealed that expression of most HSPs were induced by high temperature. However, every subfamily showed different expression suggesting distinctive role in heat stress tolerance. WcHSP70-4, WcHSP90-1, and WcHSP100-1 showed the highest response to high temperature stress. Heterologous expression of WcHSP70-4, WcHSP90-1, and WcHSP100-1 genes in Escherichia coli enhanced survival rate of E. coli during heat stress. These findings suggest the role of W. cocos heat shock genes in the high temperature stress tolerance.
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P1 -like phage-plasmids (PPs) are important gene vehicles in isolated pathogens. In this study, we conducted genome-wide and cross-species analysis of antimicrobial resistance genes (ARGs) from 35 ARG-positive P1-like PPs. LS-BSR analysis reveal that P1-like PPs had in common 7 highly variable regions and carried 48 different ARG subtypes. The most prevalent gene groups were the colistin resistance gene mcr-1 and a class 1 integron. Analysis of the flanking sequences of mcr-1 indicated an "IS30-mcr-1-ORF-IS30" as the core cluster. In particular, we found an mcr-1- and blaCTX-M-55-coharboring large fusion P1-like PP. Also, tet(X4) was detected and flanking sequences indicated tet(X4)-bearing cluster can formed a larger size fusion plasmid mediated a wider spread via IS26 hotspots. Overall, this study demonstrated that P1-like PPs can not only mobilize a large number of ARGs in variable regions but also form larger hybrid P1-like PPs that would increase their ability to spread antimicrobial resistance.
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Antibacterianos , Bacteriófagos , Antibacterianos/farmacología , Enterobacteriaceae/genética , Bacteriófagos/genética , Farmacorresistencia Bacteriana/genética , PlásmidosRESUMEN
As antimicrobial resistance (AMR) continues to increase, the therapeutic use of phages has re-emerged as an attractive alternative. However, knowledge of phage resistance development and bacterium-phage interaction complexity are still not fully interpreted. In this study, two lytic T4-like and T7-like phage infecting model Escherichia coli strain C600 are selected, and host genetic determinants involved in phage susceptibility and resistance are also identified using TraDIS strategy. Isolation and identification of the lytic T7-like show that though it belongs to the phage T7 family, genes encoding replication and transcription protein exhibit high differences. The TraDIS results identify a huge number of previously unidentified genes involved in phage infection, and a subset (six in susceptibility and nine in resistance) are shared under pressure of the two kinds of lytic phage. Susceptible gene wbbL has the highest value and implies the important role in phage susceptibility. Importantly, two susceptible genes QseE (QseE/QseF) and RstB (RstB/RstA), encoding the similar two-component system sensor histidine kinase (HKs), also identified. Conversely and strangely, outer membrane protein gene ompW, unlike the gene ompC encoding receptor protein of T4 phage, was shown to provide phage resistance. Overall, this study exploited a genome-wide fitness assay to uncover susceptibility and resistant genes, even the shared genes, important for the E. coli strain of both most popular high lytic T4-like and T7-like phages. This knowledge of the genetic determinants can be further used to analysis the behind function signatures to screen the potential agents to aid phage killing of MDR pathogens, which will greatly be valuable in improving the phage therapy outcome in fighting with microbial resistance.
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Proteínas de Escherichia coli , Escherichia coli , Interacciones Microbiota-Huesped , Fagos T , Bacteriófago T7/genética , Bacteriófago T7/inmunología , Proteínas de Unión al ADN , Escherichia coli/genética , Escherichia coli/inmunología , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/inmunología , Receptores Adrenérgicos , Bacteriófago T4/genética , Bacteriófago T4/inmunología , Fagos T/genética , Fagos T/inmunología , Interacciones Microbiota-Huesped/genética , Interacciones Microbiota-Huesped/inmunologíaRESUMEN
Obesity can activate the inflammatory signal pathway, induce in the body a state of chronic inflammation, and increase the excitability of the sympathetic nervous system, which may induce sympathetic neuropathic injury. The stellate sympathetic ganglia (SG) can express the P2X4 receptor, and the abnormal expression of the P2X4 receptor is related to inflammation. Imperatorin (IMP) is a kind of furan coumarin plant which has anti-inflammatory effects. This project aimed to investigate whether IMP can affect the expression of P2X4 receptors in the SG of obese rats to display a protective effect from high-fat-triggered cardiac sympathetic neuropathic injury. Molecular docking through homology modelling revealed that IMP had good affinity for the P2X4 receptor. Our results showed that compared with the normal group, the administration of IMP or P2X4 shRNA decreased sympathetic excitement; reduced the serum levels of triglyceride, total cholesterol, and lactate dehydrogenase; downregulated the expression of P2X4 receptors in SG; and inhibited the expression of inflammatory factors in the SG and serum of obese rats significantly. In addition, the expression of factors associated with the cell pyroptosis GSDMD, caspase-1, NLRP-3, and IL-18 in obese rats were significantly higher than those of the normal rats, and such effects were decreased after treatment with IMP or P2X4 shRNA. Furthermore, IMP significantly reduced the ATP-activated currents in HEK293 cells transfected with P2X4 receptor. Thus, the P2X4 receptor may be a key target for the treatment of obesity-induced cardiac sympathetic excitement. IMP can improve obesity-induced cardiac sympathetic excitement, and its mechanism of action may be related to the inhibition of P2X4 receptor expression and activity in the SG, suppression of cellular pyroptosis in the SG, and reduction of inflammatory factor levels.
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Receptores Purinérgicos P2X4 , Ganglio Estrellado , Ratas , Humanos , Animales , Ratas Sprague-Dawley , Receptores Purinérgicos P2X4/genética , Receptores Purinérgicos P2X4/metabolismo , Células HEK293 , Simulación del Acoplamiento Molecular , Ganglio Estrellado/metabolismo , ARN Interferente Pequeño/metabolismoRESUMEN
The P1-like phage plasmid (PP) has been widely used as a molecular biology tool, but its role as an active accessory cargo element is not fully understood. In this study, we provide insights into the structural features and gene content similarities of 77 P1-like PPs in the RefSeq database. We also describe a P1-like PP carrying a blaCTX-M-55 gene, JL22, which was isolated from a clinical strain of Escherichia coli from a duck farm. P1-like PPs were very similar and conserved based on gene content similarities, with only eight highly variable regions. Importantly, two kinds of replicon types, namely, IncY and p0111, were identified and can be used to specifically identify the P1-like phage. JL22 is similar to P1, acquiring an important foreign DNA fragment with two obvious features, namely, the plasmid replication gene repA' (p0111) replacing the gene repA (IncY) and a 4,200-bp fragment mobilized by IS1380 and IS5 and containing a blaCTX-M-55 gene and a trpB gene encoding tryptophan synthase (indole salvaging). The JL22 phage could be induced but had no lytic capacities. However, a lysogenic recipient and intact structure of JL22 virions were observed, showing that the extended-spectrum ß-lactamase blaCTX-M-55 gene was successfully transferred. Overall, conserved genes can be a good complement to improve the identification efficiency and accuracy in future screening for P1-like PPs. Moreover, the highly conserved structures may be important for their prevalence and dissemination. IMPORTANCE As a PP, P1 DNA exists as a low-copy-number plasmid and replicates autonomously with a lysogenization style. This unique mode of P1-like elements probably indicates a stable contribution to antibiotic resistance. After analyzing these elements, we show that P1-like PPs are very similar and conserved, with only eight highly variable regions. Moreover, we observed the occurrence of replicon IncY and p0111 only in the P1-like PP community, implying that these conserved regions, coupled with IncY and p0111, can be an important complement in future screening of P1-like PPs. Identification and characterization of JL22 confirmed our findings that major changes were located in variable regions, including the first detection of blaCTX-M-55 in such a mobile genetic element. This suggests that these variable regions may facilitate foreign DNA mobilization. This study features a comprehensive genetic analysis of P1-like PPs, providing new insights into the dissemination mechanisms of antibiotic resistance through P1 PPs.
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Bacteriófagos , Triptófano Sintasa , beta-Lactamasas/genética , Bacteriófagos/genética , Triptófano Sintasa/genética , Plásmidos/genética , Escherichia coli , Indoles , Antibacterianos/farmacologíaRESUMEN
Chronic visceral pain can occur in many disorders, the most common of which is irritable bowel syndrome (IBS). Moreover, depression is a frequent comorbidity of chronic visceral pain. The P2X7 receptor is crucial in inflammatory processes and is closely connected to developing pain and depression. Gallic acid, a phenolic acid that can be extracted from traditional Chinese medicine, has been demonstrated to be anti-inflammatory and anti-depressive. In this study, we investigated whether gallic acid could alleviate comorbid visceral pain and depression by reducing the expression of the P2X7 receptor. To this end, the pain thresholds of rats with comorbid visceral pain and depression were gauged using the abdominal withdraw reflex score, whereas the depression level of each rat was quantified using the sucrose preference test, the forced swimming test, and the open field test. The expressions of the P2X7 receptor in the hippocampus, spinal cord, and dorsal root ganglion (DRG) were assessed by Western blotting and quantitative real-time PCR. Furthermore, the distributions of the P2X7 receptor and glial fibrillary acidic protein (GFAP) in the hippocampus and DRG were investigated in immunofluorescent experiments. The expressions of p-ERK1/2 and ERK1/2 were determined using Western blotting. The enzyme-linked immunosorbent assay was utilized to measure the concentrations of IL-1ß, TNF-α, and IL-10 in the serum. Our results demonstrate that gallic acid was able to alleviate both pain and depression in the rats under study. Gallic acid also reduced the expressions of the P2X7 receptor and p-ERK1/2 in the hippocampi, spinal cords, and DRGs of these rats. Moreover, gallic acid treatment decreased the serum concentrations of IL-1ß and TNF-α, while raising IL-10 levels in these rats. Thus, gallic acid may be an effective novel candidate for the treatment of comorbid visceral pain and depression by inhibiting the expressions of the P2X7 receptor in the hippocampus, spinal cord, and DRG.
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Dolor Visceral , Animales , Depresión/tratamiento farmacológico , Ácido Gálico/farmacología , Hiperalgesia/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores Purinérgicos P2X7/genética , Factor de Necrosis Tumoral alfa/metabolismo , Dolor Visceral/tratamiento farmacológicoRESUMEN
Archaea exhibit strong community heterogeneity with microhabitat gradients and are a non-negligible part of biocrust's microorganisms. The study on archaeal biogeography in biocrusts could provide new insights for its application in environmental restoration. However, only a few studies on assembly processes and co-occurrence patterns of the archaeal community in patchy biocrusts have been reported, especially considering the number of species pools (SPs). Here, we comprehensively collected biocrusts across 3,500 km of northern China. Different successional biocrusts from various regions contain information of local climate and microenvironments, which can shape multiple unique archaeal SPs. The archaeal community differences in the same successional stage exceeded the variations between successional stages, which was due to the fact that the heterogeneous taxa tended to exchange between unknown patches driven by drift. We also comparatively studied the driving forces of community heterogeneity across three to ten SPs, and assembly and co-occurrence patterns were systematically analyzed. The results revealed that the impact of spatial factors on biogeographic patterns was greater than that of environmental and successional factors and that impact decreased with the number of SPs considered. Meanwhile, community heterogeneity at the phylogenetic facet was more sensitive to these driving factors than the taxonomic facet. Subgroups 1 (SG1) and 2 (SG2) of the archaeal communities in biocrusts were dominated by Nitrososphaeraceae and Haloarchaea, respectively. The former distribution pattern was associated with non-salinity-related variables and primarily assembled by drift, whereas the latter was associated with salinity-related variables and primarily assembled by homogeneous selection. Finally, network analysis indicated that the SG1 network had a higher proportion of competition and key taxa than the SG2 network, but the network of SG2 was more complex. Our study suggested that the development of the archaeal community was not consistent with biocrusts succession. The dominant taxa may determine the patterns of community biogeography, assembly, and co-occurrence.