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Introduction: The dissemination of strains producing tetracyclines monooxygenase Tet(X) from breeding farms to the natural environment poses a potential threat to public health. Methods: Antimicrobial susceptibility testing and WGS were performed to identify resistance phenotypes and genotypes. Cloning experiments, sequence alignment, and homology modeling were used to characterize the function and formation mechanisms of the recombinant variant. The mobilization potential of Tet(X) was assessed by collinearity analysis, conjugation experiments, and phylogenetic analysis. Results: Three tet(X)-producing Elizabethkingia meningoseptica strains were isolated from bullfrog breeding ponds, the sewage outlet, and downstream river in Zhejiang Province, China. These strains carry a novel Tet(X) variant, differing from Tet(X6) by seven residues, and possess the ability to degrade tetracyclines. Interestingly, the novel Tet(X) is a recombinant variant formed by homologous recombination of Tet(X6) and the C-terminal of Tet(X2). Further analysis revealed that Tet(X6) formed several Tet(X) variants, including Tet(X5), through homologous recombination. The novel tet(X) gene is located on a circularizable integrative and conjugative element (ICEEmeChn3), with ISwz1 participating in the recombination of its multi-drug resistance region, potentially facilitating the mobilization and recombination of tet(X) in early hosts. These three strains were clonally transmitted and shared a close genetic relationship (SNP < 62) with a clinically-sourced strain isolated from the same province. Discussion: To our knowledge, this is the first report of homologous recombination between Tet(X) variants with differing activities. These clonal strains provide evidence of the transmission of tet(X)-positive strains from aquaculture sewage to the natural environment, highlighting the need to strengthen the monitoring and management of this emerging farming model.
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Intestinal pathogenic Escherichia coli (InPEC) is one of the most common causes of bacterial diarrhea in farm animals, including profuse neonatal diarrhea and post weaning diarrhea (PWD) in piglets. In this study, we investigated the prevalence of InPEC and associated primary virulence factors among 543 non-duplicate E. coli isolates from diarrheal pigs from 15 swine farms in southern China. Six major virulence genes associated with InPEC were identified among 69 (12.71â¯%) E. coli isolates and included est (6.62â¯%), K88 (4.79â¯%), elt (3.68â¯%), eae (1.47â¯%), stx2 (0.92â¯%) and F18 (0.55â¯%). Three pathotypes of InPEC were identified including ETEC (8.10â¯%), EPEC (1.29â¯%) and STEC/ETEC (0.92â¯%). In particular, K88 was only found in ETEC from breeding farms, whereas F18 was only present in STEC/ETEC hybrid from finishing farms. Whole genome sequence analysis of 37 E. coli isolates revealed that InPEC strains frequently co-carried multiple antibiotic resistance gene (ARG). est, elt and F18 were also found to co-locate with ARGs on a single IncFIB/IncFII plasmid. InPEC isolates from different pathotypes also possessed different profiles of virulence genes and antimicrobial resistance genes. Population structure analysis demonstrated that InPEC isolates from different pathotypes were highly heterogeneous whereas those of the same pathotype were extremely similar. Plasmid analysis revealed that K88 and/or est/elt were found on pGX18-2-like/pGX203-2-like and pGX203-1-like IncFII plasmids, while F18 and elt/est, as well as diverse ARGs were found to co-locate on IncFII/IncFIB plasmids with a non-typical backbone. Moreover, these key virulence genes were flanked by or adjacent to IS elements. Our findings indicated that both clonal expansion and horizontal spread of epidemic IncFII plasmids contributed to the prevalence of InPEC and the specific virulence genes (F4, F18, elt and est) in the tested swine farms.
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Diarrea , Infecciones por Escherichia coli , Escherichia coli , Enfermedades de los Porcinos , Factores de Virulencia , Animales , Porcinos , Enfermedades de los Porcinos/microbiología , Enfermedades de los Porcinos/epidemiología , China/epidemiología , Infecciones por Escherichia coli/veterinaria , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/epidemiología , Diarrea/microbiología , Diarrea/veterinaria , Diarrea/epidemiología , Prevalencia , Factores de Virulencia/genética , Escherichia coli/genética , Escherichia coli/patogenicidad , Escherichia coli/aislamiento & purificación , Escherichia coli/clasificación , Virulencia/genética , Intestinos/microbiología , Secuenciación Completa del Genoma , Escherichia coli Enterotoxigénica/genética , Escherichia coli Enterotoxigénica/patogenicidad , Escherichia coli Enterotoxigénica/aislamiento & purificación , Proteínas de Escherichia coli/genéticaRESUMEN
PURPOSE: To investigate how passive hyperthermia affect the resting-state functional brain activity based on an acute mouse model after heat stress exposure. MATERIALS AND METHODS: Twenty-eight rs-fMRI data of C57BL/6J male mice which weighing about 24 â¼ 29 g and aged 12 â¼ 16 weeks were collected. The mice in the hyperthermia group (HT, 40 °C ± 0.5 °C, 40 min) were subjected to passive hyperthermia before the anesthesia preparation for scanning. While the normal control group (NC) was subjected to normothermia condition (NC, 20 °C ± 2 °C, 40 min). After data preprocessing, we performed independent component analysis (ICA) and region of interested (ROI)-ROI functional connectivity (FC) analyses on the data of both HT (n = 13) and NC (n = 15). RESULTS: The group ICA analysis showed that the HT and the NC both included 11 intrinsic connectivity networks (ICNs), and can be divided into four types of networks: the cortical network (CN), the subcortical network (SN), the default mode network (DMN), and cerebellar networks. CN and SN belongs to sensorimotor network. Compared with NC, the functional network organization of ICNs in the HT was altered and the overall functional intensity was decreased. Furthermore, 13 ROIs were selected in CN, SN, and DMN for further ROI-ROI FC analysis. The ROI-ROI FC analysis showed that passive hyperthermia exposure significantly reduced the FC strength in the overall brain represented by CN, SN, DMN of mice. CONCLUSION: Prolonged exposure to high temperature has a greater impact on the overall perception and cognitive level of mice, which might help understand the relationship between neuronal activities and physiological thermal sensation and regulation as well as behavioral changes.
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Encéfalo , Hipertermia , Ratones Endogámicos C57BL , Animales , Ratones , Masculino , Encéfalo/fisiopatología , Encéfalo/diagnóstico por imagen , Hipertermia/fisiopatología , Imagen por Resonancia Magnética/métodosRESUMEN
BACKGROUND: Plant microbiota contributes to plant growth and health, including enhancing plant resistance to various diseases. Despite remarkable progress in understanding diseases resistance in plants, the precise role of rhizosphere microbiota in enhancing watermelon resistance against soil-borne diseases remains unclear. Here, we constructed a synthetic community (SynCom) of 16 core bacterial strains obtained from the rhizosphere of grafted watermelon plants. We further simplified SynCom and investigated the role of bacteria with synergistic interactions in promoting plant growth through a simple synthetic community. RESULTS: Our results demonstrated that the SynCom significantly enhanced the growth and disease resistance of ungrafted watermelon grown in non-sterile soil. Furthermore, analysis of the amplicon and metagenome data revealed the pivotal role of Pseudomonas in enhancing plant health, as evidenced by a significant increase in the relative abundance and biofilm-forming pathways of Pseudomonas post-SynCom inoculation. Based on in vitro co-culture experiments and bacterial metabolomic analysis, we selected Pseudomonas along with seven other members of the SynCom that exhibited synergistic effects with Pseudomonas. It enabled us to further refine the initially constructed SynCom into a simplified SynCom comprising the eight selected bacterial species. Notably, the plant-promoting effects of simplified SynCom were similar to those of the initial SynCom. Furthermore, the simplified SynCom protected plants through synergistic effects of bacteria. CONCLUSIONS: Our findings suggest that the SynCom proliferate in the rhizosphere and mitigate soil-borne diseases through microbial synergistic interactions, highlighting the potential of synergistic effects between microorganisms in enhancing plant health. This study provides a novel insight into using the functional SynCom as a promising solution for sustainable agriculture. Video Abstract.
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Citrullus , Fusarium , Microbiota , Enfermedades de las Plantas , Pseudomonas , Rizosfera , Microbiología del Suelo , Citrullus/microbiología , Fusarium/genética , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Pseudomonas/genética , Resistencia a la Enfermedad , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Raíces de Plantas/microbiologíaRESUMEN
Salmonella 4,[5],12:i:-, a monophasic variant of Salmonella Typhimurium, has emerged as a global cause of multidrug-resistant salmonellosis and has become endemic in many developing and developed countries, especially in China. Here, we have sequenced 352 clinical isolates in Guangdong, China, during 2009-2019 and performed a large-scale collection of Salmonella 4,[5],12:i:- with whole genome sequencing (WGS) data across the globe, to better understand the population structure, antimicrobial resistance (AMR) genomic characterization, and transmission routes of Salmonella 4,[5],12:i:- across Guangdong. Salmonella 4,[5],12:i:- strains showed broad genetic diversity; Guangdong isolates were found to be widely distributed among the global lineages. Of note, we identified the formation of a novel Guangdong clade (Bayesian analysis of population structure lineage 1 [BAPS1]) genetically diversified from the global isolates and likely emerged around 1990s. BAPS1 exhibits unique genomic features, including large pan-genome, decreased ciprofloxacin susceptibility due to mutation in gyrA and carriage of plasmid-mediated quinolone resistance (PMQR) genes, and the multidrug-resistant IncHI2 plasmid. Furthermore, high genetic similarity was found between strains collected from Guangdong, Europe, and North America, indicating the association with multiple introductions from overseas. These results suggested that global dissemination and local clonal expansion simultaneously occurred in Guangdong, China, and horizontally acquired resistance to first-line and last-line antimicrobials at local level, underlying emergences of extensive drug and pan-drug resistance. Our findings have increased the knowledge of global and local epidemics of Salmonella 4,[5],12:i:- in Guangdong, China, and provided a comprehensive baseline data set essential for future molecular surveillance.IMPORTANCESalmonella 4,[5],12:i:- has been regarded as the predominant pandemic serotype causing diarrheal diseases globally, while multidrug resistance (MDR) constitutes great public health concerns. This study provided a detailed and comprehensive genome-scale analysis of this important Salmonella serovar in the past decade in Guangdong, China. Our results revealed the complexity of two distinct transmission modes, namely global transmission and local expansion, circulating in Guangdong over a decade. Using phylogeography models, the origin of Salmonella 4,[5],12:i:- was predicted from two aspects, year and country, that is, Salmonella 4,[5],12:i:- emerged in 1983, and was introduced from the UK, and subsequently differentiated into the local endemic lineage circa 1991. Additionally, based on the pan-genome analysis, it was found that the gene accumulation rate in local endemic BAPS 1 lineage was higher than in other lineages, and the horizontal transmission of MDR IncHI2 plasmid associated with high resistance played a major role, which showed the potential threat to public health.
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Farmacorresistencia Bacteriana Múltiple , Infecciones por Salmonella , Secuenciación Completa del Genoma , China/epidemiología , Farmacorresistencia Bacteriana Múltiple/genética , Humanos , Infecciones por Salmonella/microbiología , Infecciones por Salmonella/epidemiología , Infecciones por Salmonella/transmisión , Infecciones por Salmonella/tratamiento farmacológico , Antibacterianos/farmacología , Genoma Bacteriano/genética , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genética , Pruebas de Sensibilidad Microbiana , Filogenia , Genómica , Plásmidos/genéticaRESUMEN
BACKGROUND: Pulmonary Fibrosis (PF) is a progressive lung disease characterized by the diffuse interstitial tissue, leading to severe breathing difficulties. The existing treatment methods are primarily aimed at slowing the progression of the disease, underscoring the urgent need to discover new drug interventions targeting novel sites. The "gut-lung axis" represents a complex bidirectional communication system where the gut microbiota not only influences lung immunity but also responds to lung-derived signals. Recent advances have uncovered that alterations in gut microbiota composition can significantly impact respiratory diseases, offering new insights into their pathogenesis and potential therapeutic approaches. METHODS: This study is based on the fundamental concepts of the lung-gut axis and our previous research, further exploring the potential mechanisms of 20(S)-Protopanaxadiol (PPD) in ginseng against PF. We utilized a bleomycin-induced mouse model of PF and employed metabolomics and 16S rRNA sequencing to investigate the pathways through which PPD regulates the pulmonary fibrosis process via the gut-lung axis. Finally, we employed strategies such as antibiotic-induced microbiota disruption and fecal microbiota transplantation (FMT) to provide a comprehensive perspective on how PPD regulates pulmonary fibrosis through gut microbiota. RESULTS: The results of the bleomycin (BLM) mouse model of PF proved that PPD can directly act on the glycolysis- related metabolic reprogramming process in lung and the AMPK/STING pathway to improve PF. Combined the analysis of gut microbiota and related metabolites, we found that PPD can regulate the process of PF through the gut-lung axis target points G6PD and SPHK1. FMT and antibiotic-induced microbiota disruption further confirmed intermediate effect of gut microbiota in PF process and the treatment of PPD. Our study suggests that PPD can alleviate the process of pulmonary fibrosis either by directly acting on the lungs or by regulating the gut microbiota. CONCLUSION: This study positions PPD as a vanguard in the therapeutic landscape for pulmonary fibrosis, offering a dual mechanism of action that encompasses both modulation of gut microbiota and direct intervention at molecular targets. These insights highlight the immense therapeutic potential of harnessing the gut-lung axis.
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Modelos Animales de Enfermedad , Microbioma Gastrointestinal , Pulmón , Ratones Endogámicos C57BL , Panax , Fibrosis Pulmonar , Sapogeninas , Animales , Sapogeninas/farmacología , Fibrosis Pulmonar/tratamiento farmacológico , Microbioma Gastrointestinal/efectos de los fármacos , Pulmón/efectos de los fármacos , Ratones , Panax/química , Bleomicina , Trasplante de Microbiota Fecal , Masculino , ARN Ribosómico 16SRESUMEN
Objective: Henoch-Schönlein purpura (HSP) is the most common systemic vasculitis in children. HSP is a multifactorial inflammatory disease, but its pathogenesis is still unclear. The pathogenicity of familial Mediterranean fever gene (MEFV) variants in HSP remains controversial. The objective of this study was to evaluate relationships between MEFV variants and susceptibility to HSP and their associations with clinical outcomes. We also investigated levels of IL-33 and soluble suppression of tumorigenicity 2 (sST2) in children with HSP and their clinical significance. Methods: We selected 100 children with HSP as the case group. The control group consisted of 50 children who visited the hospital for physical health examinations. All subjects were screened for MEFV gene exon mutations, and levels of IL-33 and sST2 were measured. Results: The frequency of MEFV variants was significantly greater in HSP patients than in healthy controls. The variant with the highest frequency was E148Q. The frequency of the C allele of the MEFV variant E148Q was 32 % in HSP patients and 18 % in controls (P-adjust = 0.04). Patients with the MEFV E148Q variant had more frequent joint involvement and recurrent purpura and higher levels of IL-33 and C-reactive protein (CRP). Levels of IL-33 and sST2 in children with HSP were significantly higher than those in the control group, and the sST2/IL-33 ratio in children with HSP was unbalanced (P-adjust <0.05). Logistic regression analysis revealed the presence of E148Q and an unbalanced sST2/IL-33 ratio to be independent risk factors for HSP. Conclusion: The results of this study suggest that the MEFV variant E148Q is associated with HSP susceptibility in Chinese children and that carriers of the variant may have more severe clinical manifestations and greater inflammatory responses. E148Q and the sST2/IL-33 ratio may play important roles in the pathogenesis of HSP.
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Warming and precipitation anomalies affect terrestrial carbon balance partly through altering microbial eco-physiological processes (e.g., growth and death) in soil. However, little is known about how such processes responds to simultaneous regime shifts in temperature and precipitation. We used the 18O-water quantitative stable isotope probing approach to estimate bacterial growth in alpine meadow soils of the Tibetan Plateau after a decade of warming and altered precipitation manipulation. Our results showed that the growth of major taxa was suppressed by the single and combined effects of temperature and precipitation, eliciting 40-90% of growth reduction of whole community. The antagonistic interactions of warming and altered precipitation on population growth were common (~70% taxa), represented by the weak antagonistic interactions of warming and drought, and the neutralizing effects of warming and wet. The members in Solirubrobacter and Pseudonocardia genera had high growth rates under changed climate regimes. These results are important to understand and predict the soil microbial dynamics in alpine meadow ecosystems suffering from multiple climate change factors.
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Microbiología del Suelo , Tibet , Lluvia , Cambio Climático , Bacterias/crecimiento & desarrollo , Bacterias/metabolismo , Suelo/química , Temperatura , Pradera , SequíasRESUMEN
BACKGROUND: Numerous studies have explored the therapeutic potential of microRNA (miR) in myocardial infarction (MI) treatment. This study focuses on the role of miR-322-5p in MI, particularly in its regulatory interaction with B-cell translocation gene 2 (BTG2). MATERIALS AND METHODS: Expression levels of miR-322-5p and BTG2 were assessed in a rat MI model. Adenovirus altering miR-322-5p or BTG2 expression were administered to MI rats. Evaluation included cardiac function, inflammation, myocardial injury, pathological changes, apoptosis, and NF-κB pathway-related genes in MI rats post-targeted treatment. The miR-322-5p and BTG2 targeting relationship was investigated. RESULTS: MI rats exhibited low miR-322-5p and high BTG2 expression in the myocardial tissues. Restoration of miR-322-5p enhanced cardiac function, alleviated inflammation and myocardial injury, mitigated pathological changes and apoptosis, and deactivated the NF-κB pathway in MI rats. BTG2 expression was negatively-regulated by miR-322-5p. Overexpressed BTG2 counteracted miR-322-5p-induced cardioprotection on MI rats. CONCLUSION: This study provides evidence that miR-322-5p protects against MI by suppressing BTG2 expression.
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Proteínas Inmediatas-Precoces , MicroARNs , Infarto del Miocardio , Animales , Masculino , Ratas , Apoptosis , Modelos Animales de Enfermedad , Proteínas Inmediatas-Precoces/genética , Proteínas Inmediatas-Precoces/metabolismo , MicroARNs/metabolismo , MicroARNs/genética , Infarto del Miocardio/genética , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , FN-kappa B/metabolismo , Ratas Sprague-Dawley , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismoRESUMEN
BACKGROUND: Prior research underscores the significant impact of remnant cholesterol (RC) on stroke occurrence due to its proatherogenic and proinflammatory traits. This study aims to explore diverse risks of new-onset stroke associated with RC, considering distinct inflammation levels in the middle-aged and senior population in China. METHODS: We analyzed 6509 participants from the China Health and Retirement Longitudinal Study (CHARLS) across four waves (2011-2018). We employed a multivariable Cox proportional hazards regression model, incorporated restricted cubic spline techniques, and conducted sensitivity analyses to evaluate the association among RC, high-sensitivity C-reactive protein (hsCRP), and the risk of new-onset stroke. RESULTS: Over 7 years, 540 new-onset strokes occurred. Individuals in the highest quartile of RC levels exhibited a heightened risk of new-onset stroke, with a multivariable-adjusted hazard ratio (HR) peaking at 1.50 (95% confidence interval 1.12-2.00, P for trend = 0.021), showing a non-linear correlation (P nonlinearity = 0.049). High hsCRP alone had an adjusted HR of 1.10 (95% CI 0.87-1.39), compared to 1.40 (95% CI 1.00-1.96) for high RC alone. Additionally, concurrent high RC and hsCRP showed an adjusted HR of 1.43 (95% CI 1.05-1.96). Consistency persisted across various hsCRP thresholds, after adjusting for additional parameters, or excluding chronic diseases in the primary model, reinforcing result robustness. CONCLUSION: Our findings reveal a substantial and non-linear association between higher baseline RC levels and an elevated risk of new-onset stroke. Moreover, elevated levels of both RC and hsCRP jointly pose the highest risk for new-onset stroke, surpassing the risk associated with each factor individually.
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Colesterol , Inflamación , Accidente Cerebrovascular , Humanos , Masculino , Femenino , China/epidemiología , Estudios Longitudinales , Persona de Mediana Edad , Anciano , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/sangre , Inflamación/sangre , Inflamación/epidemiología , Colesterol/sangre , Jubilación , Factores de Riesgo , Biomarcadores/sangre , Estudios de SeguimientoRESUMEN
This study investigates the behaviors and effects of F-53B, an alternative to perfluorooctane sulfonate on anaerobic ammonium oxidation (anammox) processes. Results showed that the nitrogen removal efficiency (NRE) reached 83.8 % at a F-53B concentration of 0.5 mg·L-1, while NRE decreased to 66.9 % with 5 mg·L-1 of F-53B. The defluorination rates of 17.8 % (0.5 mg·L-1) and 9.3 % (5 mg·L-1) were observed, respectively, suggesting the occurrence of F-53B degradation. The relative abundance of Ca. Kuenenia decreased from 26.1 % to 16.2 % with the F-53B concentration increasing from 0.5 mg·L-1 to 5 mg·L-1. Meanwhile, Denitratisoma was selectively enriched with a relative abundance of 40.7 % at an F-53B concentration of 0.5 mg·L-1. Ca. Kuenenia could reduce reactive oxygen species induced by F-53B to maintain the balance of oxidative stress. This study gains insight into the behaviors and metabolic mechanisms of F-53B in anammox consortia, suggesting the feasibility of anammox processes for industrial wastewater.
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Oxidación Anaeróbica del Amoníaco , Éter , Animales , Éter/metabolismo , Desnitrificación , Pez Cebra/metabolismo , Alcanosulfonatos/metabolismo , Nitrógeno/metabolismo , Oxidación-Reducción , Reactores BiológicosRESUMEN
The prognosis of patients with nonvalvular atrial fibrillation (NVAF) with a low CHA2DS2-VASc score (0-1) following a stroke is not well studied. In this investigation, stroke risk factors and prognostic markers in low-risk NVAF patients who are nonetheless at risk for stroke were examined.From January 2012 to January 2022, we retrospectively assessed atrial fibrillation (AF) patients at Xiamen University's Zhongshan Hospital for ischemic stroke. Along with a control group of patients with CHA2DS2-VASc scores of 0-1 who weren't suffering from a stroke, patients with CHA2DS2-VASc scores of 0-1 at the time of stroke were included in the study. Using multivariate logistic regression, independent risk factors were identified. To assess the cumulative occurrences of in-hospital mortality in patients with NVAF-related stroke, the Kaplan-Meier method was used.The study included 156 out of 3.237 inpatients with AF-related stroke who had CHA2DS2-VASc ratings of 0-1. Left atrial diameter (LAD) (odds ratio [OR]: 1.858, 95% confidence interval (CI) 1.136-3.036, P = 0.013), D-dimer (OR: 2.569, 95% CI 1.274-5.179, P = 0.008), and NT-proBNP (OR: 4.558, 95% CI 2.060-10.087, P = 0.000) were found to be independent risk factors for stroke in NVAF patients with a low CHA2DS2-VASc score. During hospitalization, nine patients with NVAF-related stroke died. In patients with NVAF-related stroke, NT-proBNP (hazard ratio: 3.504, 95% CI 1.079-11.379, P = 0.037) was an indicator of mortality risk.Patients with NVAF and CHA2DS2-VASc scores of 0-1 had independent risk factors for stroke in the form of LAD, D-dimer, and NT-proBNP. Notably, in low-risk NVAF patients with stroke, NT-proBNP was discovered to be a potent predictor of in-hospital death.
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Fibrilación Atrial , Accidente Cerebrovascular , Humanos , Pronóstico , Estudios Retrospectivos , Mortalidad Hospitalaria , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Medición de RiesgoRESUMEN
Disco Interacting Protein 2 Homolog A (DIP2A) is expressed throughout the body and abundantly expressed in the brain tissue. It is activated by Follistatin-like 1 (FSTL1). Activated DIP2A interacts with several pathways, such as AMPK/mTOR and AKT pathways, to contribute to many biological processes, such as oxidative stress, transcriptional regulation, and apoptosis. Dysregulated DIP2A activation has been implicated in numerous processes in the brain. If the upstream pathways of DIP2A remain globally unexplored, many proteins, including cortactin, AMPK, and AKT, have been identified as its downstream targets in the literature. Recent studies have linked DIP2A to a variety of mechanisms in many types of brain disorders, suggesting that regulation of DIP2A could provide novel diagnostic and therapeutic approaches for brain disorders. In this review, we comprehensively summarized and discussed the current research on DIP2A in various brain disorders, such as stroke, autism spectrum disorders (ASD), Alzheimer's disease (AD), dyslexia, and glioma.
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Encefalopatías , Proteínas Relacionadas con la Folistatina , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Proteínas Nucleares/genética , Regulación de la Expresión Génica , Proteínas Relacionadas con la Folistatina/metabolismoRESUMEN
AIMS: Idiopathic pulmonary fibrosis (IPF) is a severe pulmonary interstitial pneumonia. Our study focuses on the role of PLA2 enzyme in the IPF to explore a more effective diagnosis and treatment mechanism of IPF. MAIN METHODS: Transcriptome data of IPF from GEO database and bleomycin-induced pulmonary fibrosis mice were analyzed to identify PLA2 enzyme and their metabolite, lysophosphatidylcholines 18:0, in IPF. Based on PLA2G2A and PLA2G2D / PLA2G2A-associated cell death genes (PCDs), the consensus clustering analysis was used to identify the subtypes of IPF and the correlation between PLA2G2A and prognosis was analyzed. The machine learning (ML) models and artificial neural network (ANN) model was used to validate the diagnostic accuracy of PLA2s and PCDs in diagnosing IPF. The gene and protein expression of NLRP3, GSDMD, and CASP-1 was estimated in recombinant PLA2G2A protein induced MLE-12 cells. KEY FINDINGS: The expression of PLA2G2D, PLA2G2A, and LPC18 significantly changed in IPF. Furtherly, PLA2G2A has a significant correlation with poor patient prognosis, which could predict the 2 or 3-years mortality rates of IPF. Two subtypes of IPF patients, identified based on PCDs, showed significant different immunoinfiltration. Recombinant PLA2G2A protein could induce the pyrotosis in the MLE-12 cell. The generalized linear model and ANN model of PLA2s or PCDs accurate diagnosis IPF. SIGNIFICANCE: PLA2G2A is the most robustly associated gene with IPF among the PLA2s, which demonstrates a potential in diagnosing and prognostic value in IPF, and provides a foundation for further understanding and breakthroughs in IPF diagnosis and treatment.
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Fibrosis Pulmonar Idiopática , Animales , Humanos , Ratones , Bleomicina , Caspasa 1 , Muerte Celular , Análisis por Conglomerados , Fosfolipasas A2 Grupo II , Fibrosis Pulmonar Idiopática/genéticaRESUMEN
Myocardial ischemia/reperfusion injury (MIRI) is a prevalent condition associated with numerous critical clinical conditions. miR-322 has been implicated in MIRI through poorly understood mechanisms. Our preliminary analysis indicated potential interaction of CREB-binding protein (CBP), a transcriptional coactivator and acetyltransferase, with HIF-1α/ß-catenin, which might regulate miR-322 expression. We, therefore, hypothesized that CBP/HIF-1α/ß-catenin/miR-322 axis might play a role in MIRI. Rat cardiomyocytes subjected to oxygen-glucose deprivation /reperfusion (OGD/R) and Langendorff perfused heart model were used to model MIRI in vitro and in vivo, respectively. We used various techniques such as CCK-8 assay, transferase dUTP nick end labeling staining, western blotting, RT-qPCR, chromatin immunoprecipitation (ChIP), dual-luciferase assay, co-immunoprecipitation (Co-IP), hematoxylin and eosin staining, and TTC staining to assess cell viability, apoptosis, and the levels of CBP, HIF-1α, ß-catenin, miR-322, and acetylation. Our results indicate that OGD/R in cardiomyocytes decreased CBP/HIF-1α/ß-catenin/miR-322 expression, increased cell apoptosis and cytokines, and reduced cell viability. However, overexpression of CBP or miR-322 suppressed OGD/R-induced cell injury, while knockdown of HIF-1α/ß-catenin further exacerbated the damage. HIF-1α/ß-catenin bound to miR-322 promoter to promote its expression, while CBP acetylated HIF-1α/ß-catenin for stabilization. Overexpression of CBP attenuated MIRI in rats by acetylating HIF-1α/ß-catenin to stabilize their expression, resulting in stronger binding of HIF-1α/ß-catenin with the miR-322 promoter and subsequent increased miR-322 levels. Therefore, activating CBP/HIF-1α/ß-catenin/miR-322 signaling may be a potential approach to treat MIRI.
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MicroARNs , Daño por Reperfusión Miocárdica , Animales , Ratas , Apoptosis , beta Catenina/genética , beta Catenina/metabolismo , Proteína de Unión a CREB/genética , Proteína de Unión a CREB/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Daño por Reperfusión Miocárdica/genética , Daño por Reperfusión Miocárdica/metabolismo , Miocitos Cardíacos/metabolismoRESUMEN
Background: Although the incidence of pressure injury in the prone position is high for the mechanically ventilated patients in the intensive care unit, evidence-based strategies are still lacking. Propose: To conduct a systematic review of current evidence, and to propose a series of strategies to prevent pressure injuries among mechanically ventilated patients with prone position in the intensive care unit. Methods: The study was guided by the Medical Research Council framework. After a systematic review of current evidence of original articles, guidelines, expert consensus and theories, a strategy draft was developed. Then we invited 20 experts to modify and refine these strategies through two rounds of Delphi consensus method. Results: After two rounds of Delphi process, the importance of coefficient of variation (Cv) and Kendall's coefficient of concordance in the strategies repository were 0.067 and 0.311, respectively. And the operability of Cv and Kendall's coefficient of concordance in the strategy draft was 0.055 and 0.294, respectively. Ultimately, we established 31 strategies for including 7 themes (assess risk factors, assess skin and tissue, body position management, skin care, nutrition, preventing medical device-related pressure injuries, education and supervision). In addition, we also developed a strategy framework to clarify our strategies. Conclusion: According to the Medical Research Council framework, we developed 7 themes and 31 strategies to prevention prone-position pressure injuries among the intensive care unit mechanically ventilated patients. This study was considered to improve the clinical management of pressure injuries among prone position patients in the intensive care unit settings.
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PURPOSE: Currently, the significance of CDKN2A/B mutations in the pathogenesis and prognosis of acute lymphoblastic leukemia (ALL) is inconclusive. In this study, we analyzed the genetic and clinical features of children with CDKN2A/B mutations in ALL. In addition, we evaluated the expression and significance of programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in serum and explored their role in the susceptibility of childhood ALL. METHODS: We sequenced CDKN2A/B in the peripheral blood of 120 children with ALL and 100 healthy children with physical examination. The levels of CD4+ T, CD8+ T, and NK cells were measured by flow cytometry (FCM). Furthermore, the expression of PD-1 and PD-L1 was detected by ELISA. RESULTS: We found 32 cases of CDKN2A rs3088440 and 11 of CDKN2B rs2069426 in 120 ALL children. Children with ALL in the CDKN2A rs3088440 were more likely to have hepatosplenomegaly (P = 0.019) and high risk (P = 0.014) than the wild group. In contrast, CDKN2B rs2069426 was more likely to develop lymph node metastasis (P = 0.017). The level of PD-L1 in the serum of ALL children was significantly higher than that of the control group, and there was no significant difference in PD-1 (P < 0.001). Additionally, children with CDKN2A rs3088440 had reduced CD8+ T cell counts than the wild group (P = 0.039). CONCLUSION: CDKN2A rs3088440 and CDKN2B rs2069426 may be related to the occurrence and development of ALL in Chinese children. Additionally, PD-1/PD-L1 may be involved in the immune escape process of ALL, which is expected to become a new target for the treatment of the disease.
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Antígeno B7-H1 , Leucemia-Linfoma Linfoblástico de Células Precursoras , Niño , Humanos , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Mutación , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Pronóstico , Receptor de Muerte Celular Programada 1/genéticaRESUMEN
Introduction: This study aimed to investigate the genetic factors promoting widespread Q6 dissemination of tet(X4) between Escherichia coli and to characterize the genetic contexts of tet(X4). Methods: We isolated E. coli from feces, water, soil and flies collected across a large-scale chicken farm in China in 2020. Antimicrobial susceptibility testing and PFGE typing were used to identify tigecycline resistance and assess clonal relationships among isolates. Plasmids present and genome sequences were analyzed by conjugation, S1 pulsed-field gel electrophoresis (PFGE), plasmid stability testing and whole-genome sequencing. Results: A total of 204 tigecycline-resistant E. coli were isolated from 662 samples. Of these, we identified 165 tet(X4)-carrying E. coli and these strains exhibited a high degree of multidrug resistance. Based on the geographical location distribution of the sampled areas, number of samples in each area and isolation rate of tigecycline-resistant strains and tet(X4)-carrying isolates, 72 tet(X4)-positive isolates were selected for further investigation. Tigecycline resistance was shown to be mobile in 72 isolates and three types of tet(X4)-carrying plasmids were identified, they were IncHI1 (n = 67), IncX1 (n = 3) and pO111-like/IncFIA(HI1) (n = 2). The pO111-like/IncFIA(HI1) is a novel plasmid capable of transferring tet(X4). The transfer efficiency of IncHI1 plasmids was extremely high in most cases and IncHI1 plasmids were stable when transferred into common recipient strains. The genetic structures flanked by IS1, IS26 and ISCR2 containing tet(X4) were complex and varied in different plasmids. Discussion: The widespread dissemination of tigecycline-resistant E. coli is a major threat to public health. This data suggests careful use of tetracycline on farms is important to limit spread of resistance to tigecycline. Multiple mobile elements carrying tet(X4) are in circulation with IncHI1 plasmids the dominant vector in this setting.
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Batch and column leaching tests were used to study thallium's release and migration behaviour and evaluate its potential toxicity risks in soil. The results indicated that leaching concentrations of Tl using TCLP and SWLP were much higher than the threshold, indicating a high risk of thallium pollution in the soil. Furthermore, the intermittent leaching rate of Tl by Ca2+ and HCl reached its maximum value, demonstrating the easy release of Tl. After HCl leaching, the form of Tl in the soil has changed, and ammonium sulfate has increased its extractability. Additionally, the extensive application of calcium promoted the release of Tl, increasing its potential ecological risk. Spectral analysis showed that Tl was mainly present in minerals such as Kaolinite and Jarosite, and exhibited significant adsorption capacity for Tl. HCl and Ca2+ damaged the crystal structure of the soil, greatly enhancing the migration and mobility of Tl in the environment. More importantly, XPS analysis confirmed that the release of Tl (I) in the soil was the leading cause of increased mobility and bioavailability. Therefore, the results revealed the risk of Tl release in the soil, providing theoretical guidance for its pollution prevention and control.
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Hericium erinaceus, a mushroom species commonly known as Yamabushitake in Japan, is known to have a stimulatory effect on neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Hericenone C, a meroterpenoid with palmitic acid as the fatty acid side chain, is reported to be one such stimulant. However, according to the structure of the compound, the fatty acid side chain seems highly susceptible to lipase decomposition, under in vivo metabolic conditions. To study this phenomenon, hericenone C from the ethanol extract of the fruiting body was subjected to lipase enzyme treatment and observed for changes in the chemical structure. The compound formed after the lipase enzyme digestion was isolated and identified using LC-QTOF-MS combined with 1H-NMR analysis. It was found to be a derivative of hericenone C without its fatty acid side chain and was named deacylhericenone. Interestingly, a comparative investigation of the neuroprotective properties of hericenone C and deacylhericenone showed that the BDNF mRNA expression in human astrocytoma cells (1321N1) and the protection against H2O2-induced oxidative stress was considerably higher in the case of deacylhericenone. These findings suggest that the stronger bioactive form of the hericenone C compound is in fact deacylhericenone.