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Actin- and microtubule (MT)-based transport systems are essential for intracellular transport. During influenza A virus (IAV) infection, MTs provide long tracks for virus trafficking toward the nucleus. However, the role of the actin cytoskeleton in IAV entry and especially the transit process is still ambiguous. Here, by using quantum dot-based single-virus tracking, it was revealed that the actin cytoskeleton was crucial for the virus entry via clathrin-mediated endocytosis (CME). After entry via CME, the virus reached MTs through three different pathways: the virus (1) was driven by myosin VI to move along actin filaments to reach MTs (AF); (2) was propelled by actin tails assembled by an Arp2/3-dependent mechanism to reach MTs (AT); and (3) directly reached MTs without experiencing actin-related movement (NA). Therefore, the NA pathway was the main one and the fastest for the virus to reach MTs. The AT pathway was activated only when plenty of viruses entered the cell. The viruses transported by the AF and AT pathways shared similar moving velocities, durations, and displacements. This study comprehensively visualized the role of the actin cytoskeleton in IAV entry and transport, revealing different pathways for IAV to reach MTs after entry. The results are of great significance for globally understanding IAV infection and the cellular endocytic transport pathway.
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Viral diseases are among the main threats to public health. Understanding the factors affecting viral invasion is important for antiviral research. Until now, it was known that most viruses have very low plaque-forming unit (PFU)-to-particle ratios. However, further investigation is required to determine the underlying factors. Here, using quantitative single-particle analysis methods, the invasion of Semliki Forest virus (SFV), Japanese encephalitis virus (JEV), and influenza A virus (IAV) containing attachment to the cell surface, entry into the cell, transport towards the cell interior, and fusion with endosomes to release nucleocapsids were quantitatively analysed in parallel. It was found that for SFV with an PFU-to-particle ratio of approximately 1:2, an entry efficiency of approximately 31% limited infection. For JEV, whose PFU-to-particle ratio was approximately 1:310, an attachment efficiency of approximately 27% and an entry efficiency of 10% were the main factors limiting its infection. Meanwhile, for IAV with PFU-to-particle ratios of 1:8100, 5% attachment efficiency, 9% entry efficiency, and 53% fusion efficiency significantly limited its infection. These results suggest that viruses with different infectivities have different limited steps in the invasion process. Moreover, there are significant differences in attachment efficiencies among viruses, emphasizing the pivotal role of attachment in viral invasion. The influence of the virus purification method on virus invasion was also investigated. This study, for the first time, reports the efficiencies of different stages of virus invasion, leading to a better understanding of virus invasion and providing a protocol to quantitatively analyse the virus invasion efficiency.
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Virus de la Influenza A , Virus de los Bosques Semliki , Internalización del Virus , Virus de la Influenza A/fisiología , Animales , Virus de los Bosques Semliki/fisiología , Humanos , Virus de la Encefalitis Japonesa (Especie)/fisiología , Línea Celular , Acoplamiento Viral , Endosomas/virologíaRESUMEN
Neohelicomyces species are a group of helicosporous hyphomycetes with the potential to produce secondary metabolites. During our investigation of helicosporous fungi, six collections were isolated from both terrestrial and freshwater habitats in Guizhou Province, China. Based on multigene phylogenetic analysis (ITS, LSU, tef1α and rpb2), coupled with morphological data, three new Neohelicomyces species, viz. N.guizhouensis, N.helicosporus and N.hydei were established. A list of accepted Neohelicomyces species with molecular data was provided. The strain of Neohelicomycespallidus (UAMH 10535) was synonymised under N.denticulatus based on molecular data.
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In high-altitude environments characterized by low pressure and oxygen levels, the intestinal microbiota undergoes significant alterations. Whether individuals are subjected to prolonged exposure or acute altitude changes, these conditions lead to shifts in both the diversity and abundance of intestinal microbiota and changes in their composition. While these alterations represent adaptations to high-altitude conditions, they may also pose health risks through certain mechanisms. Changes in the intestinal microbiota induced by high altitudes can compromise the integrity of the intestinal mucosal barrier, resulting in gastrointestinal dysfunction and an increased susceptibility to acute mountain sickness (AMS). Moreover, alterations in the intestinal microbiota have been implicated in the induction or exacerbation of chronic heart failure. Targeted modulation of the intestinal microbiota holds promise in mitigating high-altitude-related cardiac damage. Dietary interventions, such as adopting a high-carbohydrate, high-fiber, low-protein, and low-fat diet, can help regulate the effects of intestinal microbiota and their metabolic byproducts on intestinal health. Additionally, supplementation with probiotics, either through dietary sources or medications, offers a means of modulating the composition of the intestinal microbiota. These interventions may offer beneficial effects in preventing and alleviating AMS following acute exposure to high altitudes.
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Diabetic individuals with diabetic cardiomyopathy (DbCM) present with abnormal myocardial structure and function. DbCM cannot be accurately diagnosed due to the lack of suitable diagnostic biomarkers. In this study, 171 eligible participants were divided into a healthy control (HC), type 2 diabetes mellitus (T2DM) patients without DbCM (T2DM), or DbCM group. Serum fibrinogen-like protein 1 (FGL-1) and other biochemical parameters were determined for all participants. Serum FGL-1 levels were significantly higher in patients with DbCM compared with those in the T2DM group and HCs. Serum FGL-1 levels were negatively correlated with left ventricular fractional shortening and left ventricular ejection fraction (LVEF) and positively correlated with left ventricular mass index in patients with DbCM after adjusting for age, sex and body mass index. Interaction of serum FGL-1 and triglyceride levels on LVEF was noted in patients with DbCM. A composite marker including serum FGL-1 and triglycerides could differentiate patients with DbCM from those with T2DM and HCs with an area under the curve of 0.773 and 0.789, respectively. Composite marker levels were negatively correlated with N-terminal B-type natriuretic peptide levels in patients with DbCM. Circulating FGL-1 may therefore be a valuable index reflecting cardiac functions in DbCM and to diagnose DbCM.
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Biomarcadores , Diabetes Mellitus Tipo 2 , Cardiomiopatías Diabéticas , Fibrinógeno , Humanos , Masculino , Femenino , Fibrinógeno/metabolismo , Fibrinógeno/análisis , Cardiomiopatías Diabéticas/sangre , Cardiomiopatías Diabéticas/diagnóstico , Biomarcadores/sangre , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Anciano , Función Ventricular Izquierda , Estudios de Casos y Controles , Volumen Sistólico , Triglicéridos/sangreRESUMEN
Inadequate reference databases in RNA-seq analysis can hinder data utilization and interpretation. In this study, we have successfully constructed a high-quality reference transcript dataset, ZjRTD1.0, for Zoysia japonica, a widely-used turfgrass with exceptional tolerance to various abiotic stress, including low temperatures and salinity. This dataset comprises 113,089 transcripts from 57,143 genes. BUSCO analysis demonstrates exceptional completeness (92.4%) in ZjRTD1.0, with reduced proportions of fragmented (3.3%) and missing (4.3%) orthologs compared to prior datasets. ZjRTD1.0 enables more precise analyses, including transcript quantification and alternative splicing assessments using public datasets, which identified a substantial number of differentially expressed transcripts (DETs) and differential alternative splicing (DAS) events, leading to several novel findings on Z. japonica's responses to abiotic stresses. First, spliceosome gene expression influenced alternative splicing significantly under abiotic stress, with a greater impact observed during low-temperature stress. Then, a significant positive correlation was found between the number of differentially expressed genes (DEGs) encoding protein kinases and the frequency of DAS events, suggesting the role of protein phosphorylation in regulating alternative splicing. Additionally, our results suggest possible involvement of serine/arginine-rich (SR) proteins and heterogeneous nuclear ribonucleoproteins (hnRNPs) in generating inclusion/exclusion isoforms under low-temperature stress. Furthermore, our investigation revealed a significantly enhanced overlap between DEGs and differentially alternatively spliced genes (DASGs) in response to low-temperature stress, suggesting a unique co-regulatory mechanism governing transcription and splicing in the context of low-temperature response. In conclusion, we have proven that ZjRTD1.0 will serve as a reliable and useful resource for future transcriptomic analyses in Z. japonica.
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Empalme Alternativo , Frío , Poaceae , Empalme Alternativo/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Poaceae/genética , Estrés Fisiológico/genética , Transcriptoma/genéticaRESUMEN
BACKGROUND: Although chronic erosive gastritis (CEG) is common, its clinical characteristics have not been fully elucidated. The lack of consensus regarding its treatment has resulted in varied treatment regimens. AIM: To explore the clinical characteristics, treatment patterns, and short-term outcomes in CEG patients in China. METHODS: We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and pathology. Patients and treating physicians completed a questionnaire regarding history, endoscopic findings, and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of treatment. RESULTS: Three thousand five hundred sixty-three patients from 42 centers across 24 cities in China were included. Epigastric pain (68.0%), abdominal distension (62.6%), and postprandial fullness (47.5%) were the most common presenting symptoms. Gastritis was classified as chronic non-atrophic in 69.9% of patients. Among those with erosive lesions, 72.1% of patients had lesions in the antrum, 51.0% had multiple lesions, and 67.3% had superficial flat lesions. In patients with epigastric pain, the combination of a mucosal protective agent (MPA) and proton pump inhibitor was more effective. For those with postprandial fullness, acid regurgitation, early satiety, or nausea, a MPA appeared more promising. CONCLUSION: CEG is a multifactorial disease which is common in Asian patients and has non-specific symptoms. Gastroscopy may play a major role in its detection and diagnosis. Treatment should be individualized based on symptom profile.
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Gastritis Atrófica , Gastritis , Infecciones por Helicobacter , Helicobacter pylori , Úlcera Gástrica , Humanos , Mucosa Gástrica/patología , Gastritis/diagnóstico , Gastritis/tratamiento farmacológico , Gastritis/epidemiología , Gastritis Atrófica/diagnóstico , Gastritis Atrófica/epidemiología , Gastritis Atrófica/patología , Gastroscopía , Infecciones por Helicobacter/patología , Estilo de Vida , Dolor , Úlcera Gástrica/patologíaRESUMEN
With the abuse of antibiotics and azoles, drug-resistant Candida albicans infections have increased sharply and are spreading rapidly, thereby significantly reducing the antifungal efficacy of existing therapeutics. Several patients die of fungal infections every year. Therefore, there is an urgent requirement to develop new drugs. Accordingly, we synthesized a series of polypyridyl ruthenium (II) complexes having the formula [Ru (NN)2 (bpm)] (PF6)2 (N-N = 2,2'-bipyridine) (bpy, in Ru1), 1,10-phenanthroline (phen, in Ru2), 4,7-diphenyl-1,10-phenanthroline (DIP, in Ru3) (bpm = 2,2'-bipyrimidine) and studied their antifungal activities. Ru3 alone had no effect on the drug-resistant strains, but Ru3 combined with fluconazole (FLC) exhibited significant antifungal activity on drug-resistant strains. A high-dose combination of Ru3 and FLC exhibited direct fungicidal activity by promoting the accumulation of reactive oxygen species and damaging the cellular structure of C. albicans. Additionally, the combination of Ru3 and FLC demonstrated potent antifungal efficacy in vivo in a mouse model of invasive candidiasis. Moreover, the combination significantly improved the survival state of mice, restored their immune systems, and reduced renal injury. These findings could provide ideas for the development of ruthenium (II) complexes as novel antifungal agents for drug-resistant microbial stains.
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Candidiasis , Rutenio , Humanos , Animales , Ratones , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Fluconazol/farmacología , Fluconazol/uso terapéutico , Candida albicans , Rutenio/farmacología , Candidiasis/tratamiento farmacológico , Pruebas de Sensibilidad MicrobianaRESUMEN
BACKGROUND: Toxic epidermal necrolysis (TEN) is a life-threatening dermatological emergency mainly induced by drug hypersensitivity reactions. Standard management includes discontinuation of culprit drug and application of immunomodulatory therapy. However, mortality remains high due to complications like septic shock and multiorgan failures. Innovative approaches for skin care are crucial. This report introduces borneol-gypsum, a traditional Chinese drug but a novel dressing serving as an adjuvant of TEN therapy, might significantly improve skin conditions and patient outcomes in TEN. CASE SUMMARY: A 38-year-old woman diagnosed with eosinophilic granulomatosis with polyangiitis experienced gangrenous complications and motor nerve involvement. After initial treatment of high-dose corticosteroids and cyclophosphamide, symptom of foot drop improved, absolute eosinophil counts decreased, while limb pain sustained. Duloxetine was added to alleviate her symptom. Subsequently, TEN developed. Additional topical application of borneol-gypsum dressing not only protected the skin lesions from infection but also significantly eased localized pain. This approach demonstrated its merit in TEN management by promoting skin healing and potentially reducing infection risks. CONCLUSION: Borneol-gypsum dressing is a promising adjuvant that could significantly improve TEN management, skin regeneration, and patient comfort.
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Acute lung injury (ALI) is a serious inflammatory disease with high morbidity and mortality. Rosavin is an anti-inflammatory and antioxidant phenylpropanoid and glucoside, which is isolated from Rhodiola rosea L. However, its potential molecular mechanisms and whether it has protective effects against lipopolysaccharide (LPS)-induced ALI remain to be elucidated. To assess the in vitro anti-inflammatory effects and anti-lung injury activity of rosavin, RAW264.7 and A549 cells were stimulated using 1 µg/mL LPS. Rosavin attenuated LPS-induced activation of the TLR-4/NF-κB signaling pathway in RAW264.7 cells and inhibited LPS-induced release of inflammatory factors in A549 cells. A mouse model of acute lung injury was constructed by intraperitoneal injection of 5 mg/kg LPS to observe the therapeutic effect of rosavin. Transcriptomics analysis and Western blot assays were utilized to verify the molecular mechanism, rosavin (20, 40, and 80 mg/kg) dose-dependently ameliorated histopathological alterations, reduced the levels of inflammatory factors, and inhibited the TLR-4/NF-κB/MAPK signaling pathway and apoptosis activation. Rosavin is a promising therapeutic candidate for acute lung injury by inhibiting the TLR-4/NF-κB/MAPK pathway.
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Lesión Pulmonar Aguda , Disacáridos , Animales , Ratones , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Antiinflamatorios/efectos adversos , Disacáridos/uso terapéutico , Lipopolisacáridos/toxicidad , Pulmón/patología , FN-kappa B/metabolismo , Receptor Toll-Like 4/metabolismoRESUMEN
Anguillid herpesvirus 1 (AngHV), the causative agent of "mucus sloughing and hemorrhagic septicemia disease", causes serious infectious diseases in farmed eel. Among the effective prevention and control strategies, vaccination is one of the most effective approaches. However, no vaccine for AngHV is available. Our study developed a formalin-inactivated AngHV vaccine and evaluated its performance in American eels. Initially, AngHV-FJ, a strain of AngHV, was inactivated completely by 0.1 % formaldehyde, mixed with adjuvant Montanide ISA 763 A VG (763A). Then, vaccines containing different amount of antigen (3 × 106 PFU, 3 × 105 PFU, 3 × 104 PFU, 3 × 103 PFU) were immunized in each American eels. The results showed that the 3 × 105 PFU/fish was the proper dose. The inactivated AngHV vaccine was proven safe for American eels by back intramuscular injection. The results of twice immunization showed that antibody production peaked in the 8th week after the first immunization, and the antibody titer was 1:64,000. Furthermore, the immunized fishes challenged with AngHV (105 PFU/ml immersion) showed a significantly lower incidence rate (33.33 %) than the control group (95.65 %). The survival of the fish in the vaccine group (94.44 %) was significantly higher than the control group (60.87 %). The relative survival rate of the vaccinated group was 85.80 %. Also, vaccine group tissue collected at 7th d post-challenge showed reduced tissue damage and a lower virus load than the control group. The expression of cytokines of IL-1ß, IFN-α, IFN-γ, Mx1, RIG-1, and IRF-3, were significantly lower in the vaccine group than the control group at the 7th and 14th d post-challenge. Overall, the formalin-inactivated AngHV vaccine was safe and had immune protective effects against AngHV infection.
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Anguilla , Enfermedades de los Peces , Animales , Vacunas de Productos Inactivados , Formaldehído/farmacología , InmunidadRESUMEN
Introduction: The purpose of this study was to monitor and record the dynamic brain activity of patients with moyamoya disease (MMD), as well as to study the relationship between brain abnormalities and presenting clinical features. Methods: A total of 16 patients with MMD (2 males and 14 females) were invited to participate in the study, as were healthy controls (HCs) with the same number and sex ratio. In this study, the dynamic amplitude of low-frequency fluctuation (dALFF) was utilized to assess changes in spontaneous brain activity. Moreover, we also used correlation analysis to study the relationship among the measured mean of dALFF, behavioral performances, and the retinal nerve fiber layer and the Hospital Anxiety and Depression Scale (HADS) score to explore the potential relationship between MMD and anxiety and depression. Results: Our study reveals that in MMD, dALFF levels decreased in the left lingual gyrus, right insula, and occipital lobe. Discussion: In this study, we found and discussed the potential relationship between the abnormal activities in multiple brain regions and related functional network disorders in patients with MMD, as well as the damage to brain regions that process emotion and vision, in the hopes of providing more ideas for the clinical diagnosis and treatment of MMD.
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Enfermedad de Moyamoya , Masculino , Femenino , Humanos , Enfermedad de Moyamoya/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Mapeo EncefálicoRESUMEN
BACKGROUND: Poverty contributes to the transmission of schistosomiasis via multiple pathways, with the insufficiency of appropriate interventions being a crucial factor. The aim of this article is to provide more economical and feasible intervention measures for endemic areas with varying levels of poverty. METHODS: We collected and analyzed the prevalence patterns along with the cost of control measures in 11 counties over the last 20 years in China. Seven machine learning models, including XGBoost, support vector machine, generalized linear model, regression tree, random forest, gradient boosting machine and neural network, were used for developing model and calculate marginal benefits. RESULTS: The XGBoost model had the highest prediction accuracy with an R2 of 0.7308. Results showed that risk surveillance, snail control with molluscicides and treatment were the most effective interventions in controlling schistosomiasis prevalence. The best combination of interventions was interlacing seven interventions, including risk surveillance, treatment, toilet construction, health education, snail control with molluscicides, cattle slaughter and animal chemotherapy. The marginal benefit of risk surveillance is the most effective intervention among nine interventions, which was influenced by the prevalence of schistosomiasis and cost. CONCLUSIONS: In the elimination phase of the national schistosomiasis program, emphasizing risk surveillance holds significant importance in terms of cost-saving.
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Moluscocidas , Esquistosomiasis , Animales , Bovinos , Esquistosomiasis/epidemiología , Esquistosomiasis/prevención & control , Esquistosomiasis/tratamiento farmacológico , Moluscocidas/farmacología , China/epidemiología , Caracoles , PrevalenciaRESUMEN
During an investigation of helicosporous fungi in China, a total of seven helicosporous hyphomycetes were obtained from decaying wood in the southern region of the country. Based on phylogenetic analyses using a combined LSU, ITS, tef1α, and rpb2 sequence matrix, in conjunction with morphological comparisons, these taxa were classified within Tubeufia (Tubeufiaceae, Tubeufiales) and were recognized as three new species, viz. Tubeufiaguttulata, T.hainanensis, and T.muriformis, as well as one new distribution record, viz. T.cocois. Evidence for these new taxa and the new record, descriptions, illustrations, notes, and phylogenetic evidence are provided for the newly collected helicosporous species.
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Purpose: The purpose of this study was to use the percent amplitude of fluctuation (PerAF) to study the changes in brain activity and nerve function of herpes zoster keratitis (HZK) patients. Methods: We recruited 20 HZK patients and 20 healthy controls (HCs). Each of these groups included ten males and ten females and were matched in weight and age. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI). The percent amplitude of fluctuation (PerAF) method was used for analysis and detected differences between the two groups in the neurological function of brain areas. We also applied the receiver operating characteristic (ROC) curve to analyze the two groups and did a correlation analysis between the PerAF value, anxiety and depression score, and visual acuity. Results: The PerAF signal at the right putamen and right precentral gyrus was significantly higher in patients than in HCs. However, the PerAF value of the left inferior temporal was lower in patients than in HCs. In addition, the HZK patients' anxiety and depression score (HADS) and visual acuity (V.A.) Log MAR negatively correlated with the PerAF value at the left inferior temporal gyrus. Conclusion: HZK patients had some changes in brain regions, and the changes were also related to their mood and visual acuity. These findings might contribute to other studies on the potential pathological mechanism, disease development, prognosis, and brain function in HZK patients.
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A systematic study of the structures and electronic properties of V2-doped silicon clusters, V2Sin-/0 (n = 7-14), was carried out by anion photoelectron spectroscopic experiments combined with theoretical calculations. According to the experimental spectra of V2Sin- (n = 7-14) clusters, the V2Si12- cluster has the highest vertical detachment energy (VDE) of 3.66 eV, while V2Si7- and V2Si14- clusters have lower VDEs of 2.81 and 2.84 eV, respectively. The most stable structure searches find that two V atoms in the V2Sin- clusters with size n = 7 and 8 are located at the surface, while V2Sin- clusters with n ≥ 9 prefer cage-like structures. Based on the analysis of the structural evolution of V2Sin- (n = 9-14) clusters, it can be clearly seen how the antihexagonal prism with one V encapsulated in the cage is gradually built from n = 9 to 12 and further developed from n = 12 to 14 with the extra silicon atoms located at the surface of the Si12 cage. The molecular orbital and the atoms in molecule analysis of the V2Sin- (n = 7-14) anions demonstrate that the strong V-V bond and the delocalized interaction between the V2 moiety and the Sin ligand play a significant role in stabilizing the cluster structures. A strong linear correlation has been found between the Wiberg bond order of the V-V bond and the electron density at the V-V bond critical points.
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Helicosporous hyphomycetes is a group of filamentous fungi that shows promising application prospects in metabolizing bioactive natural compounds. During a study of helicosporous fungi in China, six new helicosporous taxa were collected and isolated from decaying wood in Guangxi Zhuang Autonomous Region, China. Morphological comparisons with multi-gene phylogenetic analyses revealed that these six taxa belong to Helicosporium (Tubeufiaceae, Tubeufiales), and they were recognized as three novel species and were named Helicosporium liuzhouense, H. multidentatum, and H. nanningense. Detailed descriptions and illustrations of the newly discovered taxa and comparisons with similar fungi are provided. In addition, a list and a key to accepted Helicosporium species are provided.
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BACKGROUND: Accumulating data indicate that N6-methyladenosine (m6A) RNA methylation and lncRNA deregulation act crucial roles in cancer progression. Heterogeneous nuclear ribonucleoprotein A2B1 (HNRNPA2B1) as an m6A "reader" has been reported to be an oncogene in multiple malignancies. We herein aimed to elucidate the role and underlying mechanism by which HNRNPA2B1-mediated m6A modification of lncRNAs contributes to non-small cell lung cancer (NSCLC). METHODS: The expression levels of HNRNPA2B1 and their association with the clinicopathological characteristics and prognosis in NSCLC were determined by RT-qPCR, Western blot, immunohistochemistry and TCGA dataset. Then, the role of HNRNPA2B1 in NSCLC cells was assessed by in vitro functional experiments and in vivo tumorigenesis and lung metastasis models. HNRNPA2B1-mediated m6A modification of lncRNAs was screened by m6A-lncRNA epi-transcriptomic microarray and verified by methylated RNA immunoprecipitation (Me-RIP). The lncRNA MEG3-specific binding with miR-21-5p was evaluated by luciferase gene report and RIP assays. The effects of HNRNPA2B1 and (or) lncRNA MEG3 on miR-21-5p/PTEN/PI3K/AKT signaling were examined by RT-qPCR and Western blot analyses. RESULTS: We found that upregulation of HNRNPA2B1 was associated with distant metastasis and poor survival, representing an independent prognostic factor in patients with NSCLC. Knockdown of HNRNPA2B1 impaired cell proliferation and metastasis in vitro and in vivo, whereas ectopic expression of HNRNPA2B1 possessed the opposite effects. Mechanical investigations revealed that lncRNA MEG3 was an m6A target of HNRNPA2B1 and inhibition of HNRNPA2B1 decreased MEG3 m6A levels but increased its mRNA levels. Furthermore, lncRNA MEG3 could act as a sponge of miR-21-5p to upregulate PTEN and inactivate PI3K/AKT signaling, leading to the suppression of cell proliferation and invasion. Low expression of lncRNA MEG3 or elevated expression of miR-21-5p indicated poor survival in patients with NSCLC. CONCLUSIONS: Our findings uncover that HNRNPA2B1-mediated m6A modification of lncRNA MEG3 promotes tumorigenesis and metastasis of NSCLC cells by regulating miR-21-5p/PTEN axis and may provide a therapeutic target for NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , MicroARNs , ARN Largo no Codificante , Humanos , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transformación Celular Neoplásica , Carcinogénesis , Fosfohidrolasa PTENRESUMEN
In recent years, blaCTX-M-55-positive Escherichia coli has been widely reported in multiple locations with an increasing trend in prevalence, yet few studies have comprehensively analyzed the transmission characteristics and epidemiological patterns of blaCTX-M-55-positive E. coli. Here, we constructed a blaCTX-M-55-positive E. coli global genomic data set as completely as possible and explored the epidemiology and potential impact of blaCTX-M-55-positive E. coli on a global scale by high-resolution bioinformatics methods. The results show that blaCTX-M-55-positive E. coli has spread widely worldwide, especially in Asia, with the rich sequence typing (ST) diversity and high proportion of auxiliary genome occupancy indicating a high degree of openness. The phylogenetic tree suggests that blaCTX-M-55-positive E. coli is frequently clonally transmitted between the three human-animal environments and often cotransmitted with fosA, mcr, blaNDM, and tet(X). The stable presence of InclI1 and InclI2 in different hosts from different sources suggests that this part of the plasmid drives the widespread transmission of blaCTX-M-55-positive E. coli. We inductively clustered all blaCTX-M-55 flanking environmental gene structures and obtained five types. Notably, "ISEcp1-blaCTX-M-55-orf477-(Tn2)" and "IS26(IS15DI)-hp-hp-blaCTX-M-55-orf477-hp-blaTEM-IS26-hp-IS26-Tn2" are dominant in "humans" and in "animals and related foods," respectively. Overall, our findings highlight the importance of whole-genome sequencing-based surveillance in exploring the transmission and evolution of blaCTX-M-55-positive E. coli in the context of "One Health," and they serve as a reminder to strengthen the surveillance of blaCTX-M-55-positive E. coli in order to address the potential risk of future large outbreaks. IMPORTANCE CTX-M-55 was first discovered in Thailand in 2004, and today, this enzyme is the most common CTX-M subtype in E. coli of animal origin in China. Thus, blaCTX-M-55-positive E. coli getting widely spread is a growing public health problem. Although prevalence surveys of blaCTX-M-55-positive E. coli in different hosts have been widely reported in recent years, they remain insufficient in "One Health" context and from a global comprehensive perspective. Here, we constructed a genomic database of 2144 blaCTX-M-55-positive E. coli and used bioinformatics methods to resolve the spread and evolution of blaCTX-M-55-positive E. coli. The results suggest a potential risk of rapid transmission of blaCTX-M-55-positive E. coli and that long-term continuous surveillance of blaCTX-M-55-positive E. coli should be emphasized.
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Infecciones por Escherichia coli , Escherichia coli , Animales , Humanos , Filogenia , beta-Lactamasas/genética , Plásmidos/genética , Infecciones por Escherichia coli/epidemiología , Genómica , Tailandia , AntibacterianosRESUMEN
We determined the prevalence and molecular characteristics of blaCTX-M-55-positive Escherichia coli (E. coli) isolated from duck-fish polyculture farms in Guangzhou, China. A total of 914 E. coli strains were isolated from 2008 duck and environmental samples (water, soil and plants) collected from four duck fish polyculture farms between 2017 and 2019. Among them, 196 strains were CTX-M-1G-positive strains by PCR, and 177 (90%) blaCTX-M-1G-producing strains were blaCTX-M-55-positive. MIC results showed that the 177 blaCTX-M-55-positive strains were highly resistant to ciprofloxacin, ceftiofur and florfenicol, with antibiotic resistance rates above 95%. Among the 177 strains, 37 strains carrying the F18:A-:B1 plasmid and 10 strains carrying the F33:A-:B- plasmid were selected for further study. Pulse field gel electrophoresis (PFGE) combined with S1-PFGE, Southern hybridization and whole-genome sequencing (WGS) analysis showed that both horizontal transfer and clonal spread contributed to dissemination of the blaCTX-M-55 gene among the E. coli. blaCTX-M-55 was located on different F18:A-:B1 plasmids with sizes between ~76 and ~173 kb. In addition, the presence of blaCTX-M-55 with other resistance genes (e.g., tetA, floR, fosA3, blaTEM, aadA5 CmlA and InuF) on the same F18:A-:B1 plasmid may result in co-selection of resistance determinants and accelerate the dissemination of blaCTX-M-55 in E. coli. In summary, the F18:A-:B1 plasmid may play an important role in the transmission of blaCTX-M-55 in E. coli, and the continuous monitoring of the prevalence and transmission mechanism of blaCTX-M-55 in duck-fish polyculture farms remains important.