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1.
Nucleic Acids Res ; 52(1): 404-419, 2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38000383

RESUMEN

The bacterial ribonuclease RNase E plays a key role in RNA metabolism. Yet, with a large substrate spectrum and poor substrate specificity, its activity must be well controlled under different conditions. Only a few regulators of RNase E are known, limiting our understanding on posttranscriptional regulatory mechanisms in bacteria. Here we show that, RebA, a protein universally present in cyanobacteria, interacts with RNase E in the cyanobacterium Anabaena PCC 7120. Distinct from those known regulators of RNase E, RebA interacts with the catalytic region of RNase E, and suppresses the cleavage activities of RNase E for all tested substrates. Consistent with the inhibitory function of RebA on RNase E, depletion of RNase E and overproduction of RebA caused formation of elongated cells, whereas the absence of RebA and overproduction of RNase E resulted in a shorter-cell phenotype. We further showed that the morphological changes caused by altered levels of RNase E or RebA are dependent on their physical interaction. The action of RebA represents a new mechanism, potentially conserved in cyanobacteria, for RNase E regulation. Our findings provide insights into the regulation and the function of RNase E, and demonstrate the importance of balanced RNA metabolism in bacteria.


Asunto(s)
Anabaena , Endorribonucleasas , Anabaena/genética , Cianobacterias/genética , Cianobacterias/metabolismo , Endorribonucleasas/genética , Endorribonucleasas/metabolismo , ARN , ARN Bacteriano/genética , ARN Bacteriano/metabolismo
2.
Nucleic Acids Res ; 52(1): 186-203, 2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38000372

RESUMEN

The ubiquitous bacterial second messenger cyclic diguanylate (c-di-GMP) coordinates diverse cellular processes through its downstream receptors. However, whether c-di-GMP participates in regulating nitrate assimilation is unclear. Here, we found that NasT, an antiterminator involved in nitrate assimilation in Pseudomonas putida, specifically bound c-di-GMP. NasT was essential for expressing the nirBD operon encoding nitrite reductase during nitrate assimilation. High-level c-di-GMP inhibited the binding of NasT to the leading RNA of nirBD operon (NalA), thus attenuating the antitermination function of NasT, resulting in decreased nirBD expression and nitrite reductase activity, which in turn led to increased nitrite accumulation in cells and its export. Molecular docking and point mutation assays revealed five residues in NasT (R70, Q72, D123, K127 and R140) involved in c-di-GMP-binding, of which R140 was essential for both c-di-GMP-binding and NalA-binding. Three diguanylate cyclases (c-di-GMP synthetases) were found to interact with NasT and inhibited nirBD expression, including WspR, PP_2557, and PP_4405. Besides, the c-di-GMP-binding ability of NasT was conserved in the other three representative Pseudomonas species, including P. aeruginosa, P. fluorescens and P. syringae. Our findings provide new insights into nitrate assimilation regulation by revealing the mechanism by which c-di-GMP inhibits nitrate assimilation via NasT.


Asunto(s)
Proteínas Bacterianas , GMP Cíclico , Nitratos , Pseudomonas putida , Proteínas Bacterianas/metabolismo , GMP Cíclico/metabolismo , Regulación Bacteriana de la Expresión Génica , Simulación del Acoplamiento Molecular , Nitratos/metabolismo , Nitrito Reductasas/genética , Nitrito Reductasas/metabolismo , Pseudomonas aeruginosa/genética , Pseudomonas putida/genética , Pseudomonas putida/metabolismo
3.
Mol Microbiol ; 121(1): 1-17, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37927230

RESUMEN

The ubiquitous bacterial second messenger c-di-GMP is synthesized by diguanylate cyclase and degraded by c-di-GMP-specific phosphodiesterase. The genome of Pseudomonas putida contains dozens of genes encoding diguanylate cyclase/phosphodiesterase, but the phenotypical-genotypical correlation and functional mechanism of these genes are largely unknown. Herein, we characterize the function and mechanism of a P. putida phosphodiesterase named DibA. DibA consists of a PAS domain, a GGDEF domain, and an EAL domain. The EAL domain is active and confers DibA phosphodiesterase activity. The GGDEF domain is inactive, but it promotes the phosphodiesterase activity of the EAL domain via binding GTP. Regarding phenotypic regulation, DibA modulates the cell surface adhesin LapA level in a c-di-GMP receptor LapD-dependent manner, thereby inhibiting biofilm formation. Moreover, DibA interacts and colocalizes with LapD in the cell membrane, and the interaction between DibA and LapD promotes the PDE activity of DibA. Besides, except for interacting with DibA and LapD itself, LapD is found to interact with 11 different potential diguanylate cyclases/phosphodiesterases in P. putida, including the conserved phosphodiesterase BifA. Overall, our findings demonstrate the functional mechanism by which DibA regulates biofilm formation and expand the understanding of the LapD-mediated c-di-GMP signaling network in P. putida.


Asunto(s)
Proteínas de Escherichia coli , Pseudomonas putida , Pseudomonas putida/genética , Pseudomonas putida/metabolismo , Hidrolasas Diéster Fosfóricas/genética , Hidrolasas Diéster Fosfóricas/metabolismo , GMP Cíclico/metabolismo , Biopelículas , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Proteínas Portadoras/metabolismo , Proteínas Bacterianas/metabolismo , Regulación Bacteriana de la Expresión Génica
4.
J Cell Mol Med ; 28(10): e18379, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38752750

RESUMEN

Gastric cancer is a prevalent and deadly malignancy, and the response to immunotherapy varies among patients. This study aimed to develop a prognostic model for gastric cancer patients and investigate immune escape mechanisms using deep machine learning and single-cell sequencing analysis. Data from public databases were analysed, and a prediction model was constructed using 101 algorithms. The high-AIDPS group, characterized by increased AIDPS expression, exhibited worse survival, genomic variations and immune cell infiltration. These patients also showed immunotherapy tolerance. Treatment strategies targeting the high-AIDPS group identified three potential drugs. Additionally, distinct cluster groups and upregulated AIDPS-associated genes were observed in gastric adenocarcinoma cell lines. Inhibition of GHRL expression suppressed cancer cell activity, inhibited M2 polarization in macrophages and reduced invasiveness. Overall, AIDPS plays a critical role in gastric cancer prognosis, genomic variations, immune cell infiltration and immunotherapy response, and targeting GHRL expression holds promise for personalized treatment. These findings contribute to improved clinical management in gastric cancer.


Asunto(s)
Algoritmos , Regulación Neoplásica de la Expresión Génica , Análisis de la Célula Individual , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/patología , Análisis de la Célula Individual/métodos , Pronóstico , Escape del Tumor/genética , Línea Celular Tumoral , Inmunoterapia/métodos , Biomarcadores de Tumor/genética , Aprendizaje Automático
5.
Clin Gastroenterol Hepatol ; 22(7): 1475-1486.e4, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38369224

RESUMEN

BACKGROUND AND AIMS: COVID-19 vaccination prevents severe disease in most patients with inflammatory bowel disease (IBD), but immunosuppressive medications can blunt serologic response. We followed adults with IBD for >1 year post-COVID-19 vaccination to describe factors associated with SARS-CoV-2 infection after vaccination, evaluate for a protective SARS-CoV-2 antibody level, characterize SARS-CoV-2 antibody persistence, and identify factors associated with humoral immune response durability. METHODS: Using a prospective cohort of COVID-19 immunized adults with IBD, we analyzed factors associated with SARS-CoV-2 infection after vaccination. We evaluated for an association between SARS-CoV-2 antibody level 12 weeks postvaccination and subsequent SARS-CoV-2 infection and assessed for a threshold of protection using receiver-operating characteristic curve analysis. We then conducted a separate analysis evaluating factors associated with persistence of SARS-CoV-2 antibodies 52 weeks postimmunization. RESULTS: Almost half (43%) of 1869 participants developed COVID-19 after vaccination, but most infections were mild, and <1% required hospitalization. Older age and corticosteroid use were associated with a decreased risk of SARS-CoV-2 infection postvaccination (50-59 years of age vs 18-29 years of age: adjusted hazard ratio, 0.57; 95% confidence interval, 0.44-0.74; steroid users vs nonusers: adjusted hazard ratio, 0.58; 95% confidence interval, 0.39-0.87). Most (98%) participants had detectable antibody levels at 52 weeks postvaccination. Antibody levels at 12 weeks and number of vaccine doses were positively associated with higher antibody levels at 52 weeks, while anti-tumor necrosis factor α therapy was negatively associated. CONCLUSIONS: COVID-19 vaccination generates an effective and durable protective response for the vast majority of adults with IBD, including vulnerable populations such as corticosteroid users and older individuals. Patients with IBD benefit from COVID-19 booster vaccination.


Asunto(s)
Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Enfermedades Inflamatorias del Intestino , SARS-CoV-2 , Humanos , COVID-19/prevención & control , COVID-19/inmunología , Masculino , Femenino , Persona de Mediana Edad , Enfermedades Inflamatorias del Intestino/inmunología , Adulto , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/inmunología , Estudios Prospectivos , Anticuerpos Antivirales/sangre , SARS-CoV-2/inmunología , Vacunación , Anciano , Adulto Joven
6.
Glob Chang Biol ; 30(1): e17147, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38273514

RESUMEN

Organo-mineral interactions have been regarded as the primary mechanism for the stabilization of soil organic carbon (SOC) over decadal to millennial timescales, and the capacity for soil carbon (C) storage has commonly been assessed based on soil mineralogical attributes, particularly mineral surface availability. However, it remains contentious whether soil C sequestration is exclusively governed by mineral vacancies, making it challenging to accurately predict SOC dynamics. Here, through a 400-day incubation experiment using 13 C-labeled organic materials in two contrasting soils (i.e., Mollisol and Ultisol), we show that despite the unsaturation of mineral surfaces in both soils, the newly incorporated C predominantly adheres to "dirty" mineral surfaces coated with native organic matter (OM), demonstrating the crucial role of organo-organic interactions in exogenous C sequestration. Such interactions lead to multilayered C accumulation that is not constrained by mineral vacancies, a process distinct from direct organo-mineral contacts. The coverage of native OM by new C, representing the degree of organo-organic interactions, is noticeably larger in Ultisol (~14.2%) than in Mollisol (~5.8%), amounting to the net retention of exogenous C in Ultisol by 0.2-1.3 g kg-1 and in Mollisol by 0.1-1.0 g kg-1 . Additionally, organo-organic interactions are primarily mediated by polysaccharide-rich microbial necromass. Further evidence indicates that iron oxides can selectively preserve polysaccharide compounds, thereby promoting the organo-organic interactions. Overall, our findings provide direct empirical evidence for an overlooked but critically important pathway of C accumulation, challenging the prevailing "C saturation" concept that emphasizes the overriding role of mineral vacancies. It is estimated that, through organo-organic interactions, global Mollisols and Ultisols might sequester ~0.1-1.0 and ~0.3-1.7 Pg C per year, respectively, corresponding to the neutralization of ca. 0.5%-3.0% of soil C emissions or 5%-30% of fossil fuel combustion globally.


Asunto(s)
Carbono , Suelo , Minerales , Polisacáridos
7.
Glob Chang Biol ; 30(1): e17102, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38273557

RESUMEN

Soil protists, the major predator of bacteria and fungi, shape the taxonomic and functional structure of soil microbiome via trophic regulation. However, how trophic interactions between protists and their prey influence microbially mediated soil organic carbon turnover remains largely unknown. Here, we investigated the protistan communities and microbial trophic interactions across different aggregates-size fractions in agricultural soil with long-term fertilization regimes. Our results showed that aggregate sizes significantly influenced the protistan community and microbial hierarchical interactions. Bacterivores were the predominant protistan functional group and were more abundant in macroaggregates and silt + clay than in microaggregates, while omnivores showed an opposite distribution pattern. Furthermore, partial least square path modeling revealed positive impacts of omnivores on the C-decomposition genes and soil organic matter (SOM) contents, while bacterivores displayed negative impacts. Microbial trophic interactions were intensive in macroaggregates and silt + clay but were restricted in microaggregates, as indicated by the intensity of protistan-bacterial associations and network complexity and connectivity. Cercozoan taxa were consistently identified as the keystone species in SOM degradation-related ecological clusters in macroaggregates and silt + clay, indicating the critical roles of protists in SOM degradation by regulating bacterial and fungal taxa. Chemical fertilization had a positive effect on soil C sequestration through suppressing SOM degradation-related ecological clusters in macroaggregate and silt + clay. Conversely, the associations between the trophic interactions and SOM contents were decoupled in microaggregates, suggesting limited microbial contributions to SOM turnovers. Our study demonstrates the importance of protists-driven trophic interactions on soil C cycling in agricultural ecosystems.


Asunto(s)
Microbiota , Suelo , Suelo/química , Arcilla , Carbono/química , Agricultura , Microbiología del Suelo
8.
Environ Sci Technol ; 58(23): 10084-10094, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38816987

RESUMEN

The preservation of soil organic carbon (OC) is an effective way to decelerate the emission of CO2 emission. However, the coregulation of pore structure and mineral composition in OC stabilization remains elusive. We employed the in situ nondestructive oxidation of OC by low-temperature ashing (LTA) combined with near edge X-ray absorption fine structure (NEXAFS), high-resolution microtomography (µ-CT), field emission electron probe microanalysis (FE-EPMA) with C-free embedding, and novel Cosine similarity measurement to investigate the C retention in different aggregate fractions of contrasting soils. Pore structure and minerals contributed equally (ca. 50%) to OC accumulation in macroaggregates, while chemical protection played a leading role in C retention with 53.4%-59.2% of residual C associated with minerals in microaggregates. Phyllosilicates were discovered to be more prominent than Fe (hydr)oxides in C stabilization. The proportion of phyllosilicates-associated C (52.0%-61.9%) was higher than that bound with Fe (hydr)oxides (45.6%-55.3%) in all aggregate fractions tested. This study disentangled quantitatively for the first time a trade-off between physical and chemical protection of OC varying with aggregate size and the different contributions of minerals to OC preservation. Incorporating pore structure and mineral composition into C modeling would optimize the C models and improve the soil C content prediction.


Asunto(s)
Carbono , Minerales , Suelo , Suelo/química , Carbono/análisis , Minerales/química , Dióxido de Carbono/análisis , China , Tomografía con Microscopio Electrónico , Monitoreo del Ambiente
9.
Environ Res ; 244: 117904, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38092239

RESUMEN

Deciphering the pivotal components of nutrient metabolism in compost is of paramount importance. To this end, ecoenzymatic stoichiometry, enzyme vector modeling, and statistical analysis were employed to explore the impact of exogenous ore improver on nutrient changes throughout the livestock composting process. The total phosphorus increased from 12.86 to 18.72 g kg-1, accompanied by a marked neutralized pH with ore improver, resulting in the Carbon-, nitrogen-, and phosphorus-related enzyme activities decreases. However, the potential C:P and N:P acquisition activities represented by ln(ßG + CB): ln(ALP) and ln(NAG): ln(ALP), were increased with ore improver addition. Based on the ecoenzymatic stoiometry theory, these changes reflect a decreasing trend in the relative P/N limitation, with pH and total phosphorus as the decisive factors. Our study showed that the practical employment of eco stoichiometry could benefit the manure composting process. Moreover, we should also consider the ecological effects from pH for the waste material utilization in sustainable agriculture.


Asunto(s)
Compostaje , Ecosistema , Animales , Estiércol , Ganado/metabolismo , Suelo , Nitrógeno/análisis , Carbono/metabolismo , Fósforo
10.
Plant Cell Rep ; 43(5): 130, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38652336

RESUMEN

KEY MESSAGE: We identify three SDEs that inhibiting host defence from Candidatus Liberibacter asiaticus psy62, which is an important supplement to the pathogenesis of HLB. Candidatus Liberibacter asiaticus (CLas) is the main pathogen of citrus Huanglongbing (HLB). 38 new possible sec-dependent effectors (SDEs) of CLas psy62 were predicted by updated predictor SignalP 5.0, which 12 new SDEs were found using alkaline phosphate assay. Among them, SDE4310, SDE4435 and SDE4955 inhibited hypersensitivity reactions (HR) in Arabidopsis thaliana (Arabidopsis, At) and Nicotiana benthamiana leaves induced by pathogens, which lead to a decrease in cell death and reactive oxygen species (ROS) accumulation. And the expression levels of SDE4310, SDE4435, and SDE4955 genes elevated significantly in mild symptom citrus leaves. When SDE4310, SDE4435 and SDE4955 were overexpressed in Arabidopsis, HR pathway key genes pathogenesis-related 2 (PR2), PR5, nonexpressor of pathogenesis-related 1 (NPR1) and isochorismate synthase 1 (ICS1) expression significantly decreased and the growth of pathogen was greatly increased relative to control with Pst DC3000/AvrRps4 treatment. Our findings also indicated that SDE4310, SDE4435 and SDE4955 interacted with AtCAT3 (catalase 3) and AtGAPA (glyceraldehyde-3-phosphate dehydrogenase A). In conclusion, our results suggest that SDE4310, SDE4435 and SDE4955 are CLas psy62 effector proteins that may have redundant functions. They inhibit ROS burst and cell death by interacting with AtCAT3 and AtGAPA to negatively regulate host defense.


Asunto(s)
Arabidopsis , Proteínas Bacterianas , Nicotiana , Enfermedades de las Plantas , Especies Reactivas de Oxígeno , Arabidopsis/microbiología , Arabidopsis/genética , Arabidopsis/metabolismo , Enfermedades de las Plantas/microbiología , Nicotiana/genética , Nicotiana/microbiología , Nicotiana/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Hojas de la Planta/microbiología , Hojas de la Planta/metabolismo , Hojas de la Planta/genética , Citrus/microbiología , Citrus/genética , Citrus/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Liberibacter/patogenicidad , Liberibacter/fisiología , Interacciones Huésped-Patógeno , Plantas Modificadas Genéticamente , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Rhizobiaceae/fisiología , Resistencia a la Enfermedad/genética
11.
Int Ophthalmol ; 44(1): 234, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38896279

RESUMEN

PURPOSE: As the epidemiological and burden trends of glaucoma are changing, it is extremely necessary to re-investigate geographical differences and trends. Here we use data from the 2019 Global burden of Disease, which aims to report the prevalence and disability-adjusted life years of glaucoma injury to assess the latest epidemiological models and trends from 1990 to 2019. METHOD: Annual case numbers, age-standardized rates of prevalence, DALYs, and their estimated annual percentage changes (EAPCs) for glaucoma between 1990 and 2019 were derived from the GBD 2019 study. The relationship between glaucoma disease burden and social demographic index (SDI) was also investigated in this study. RESULTS: In 2019, there were 7.47 million prevalent cases and 0.75 million DALYs cases, which increased by 92.53% and 69.23% compared with 1990 respectively. The global age-standardized rate of prevalence (ASPR) and age-standardized rate of DALYs (ASDR) decreased during 1990-2019 (EAPC = - 0.55 and - 1, respectively). In 2019, the highest ASPR and ASDR of Glaucoma were all observed in Mali, whereas the lowest occurred in Taiwan (Province of China). In terms of gender, males were more likely to suffer from glaucoma than females, especially the elderly. CONCLUSIONS: The global prevalence and DALYs of glaucoma had an absolute increase during the past 30 years. The disease burden caused by glaucoma is closely related to socioeconomic level, age, gender, and other factors, and these findings provide a basis for policymakers from the perspective of social management.


Asunto(s)
Glaucoma , Carga Global de Enfermedades , Salud Global , Humanos , Glaucoma/epidemiología , Prevalencia , Femenino , Masculino , Persona de Mediana Edad , Anciano , Adulto , Distribución por Edad , Años de Vida Ajustados por Discapacidad , Distribución por Sexo , Años de Vida Ajustados por Calidad de Vida , Adolescente , Anciano de 80 o más Años , Adulto Joven , Niño , Costo de Enfermedad , Ceguera/epidemiología , Ceguera/etiología
12.
J Cell Mol Med ; 27(24): 4118-4132, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37830241

RESUMEN

N6 -methyladenosine (m6 A) modification represents the most abundant internal methylation of eukaryotic RNAs. KIAA1429 acts as a key component of the m6 A methyltransferase complex, but its function and mechanism in ferroptotic cell death of hepatocellular carcinoma (HCC) are barely defined. We found that KIAA1429 suppression triggered ferroptosis in HCC cells according to increased cell death, iron and MDA levels, C11-BODIPY-positive cells, ROS production and decreased GSH level. Ferroptosis inhibitors ferrostatin-1 (0.5 µM) and liproxstatin-1 (10 µM) blocked KIAA1429 suppression-induced ferroptosis of HCC cells. In addition, overexpressed KIAA1429 notably heightened the activity of cystine/glutamate antiporter (SLC7A11). SLC7A11 up-regulation partially hindered KIAA1429 inhibition-mediated ferroptosis of HCC cells. The regulation SLC7A11 by KIAA1429 was attenuated by global m6 A inhibitor cycloleucine (40 µM). RNA immunoprecipitation confirmed the binding of KIAA1429 to m6 A on SLC7A11 transcript. Additionally, it was proven that KIAA1429 inhibition mitigated HCC growth in subcutaneous xenograft mice through SLC7A11. Altogether, our findings first propose that KIAA1429 protects HCC cells from ferroptosis with a m6 A-dependent post-transcriptional modification of SLC7A11 and offer a novel insight into the dysregulated epi-transcriptomics in the context of HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Proteínas de Unión al ARN , Animales , Humanos , Ratones , Sistema de Transporte de Aminoácidos y+/genética , Carcinoma Hepatocelular/genética , Muerte Celular , Línea Celular , Ácido Glutámico , Neoplasias Hepáticas/genética , Proteínas de Unión al ARN/metabolismo
13.
Am J Gastroenterol ; 118(1): 129-137, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36114773

RESUMEN

INTRODUCTION: Children with inflammatory bowel disease (IBD) may respond differently to COVID-19 immunization as compared with healthy children or adults with IBD. Those younger than 12 years receive a lower vaccine dose than adults. We sought to describe the safety and humoral immune response to COVID-19 vaccine in children with IBD. METHODS: We recruited children with IBD, ages 5-17 years, who received ≥ 2 doses of the BNT162b2 vaccine by a direct-to-patient outreach and at select sites. Patient demographics, IBD characteristics, medication use, and vaccine adverse events were collected. A subset of participants had quantitative measurement of anti-receptor binding domain IgG antibodies after 2-part immunization. RESULTS: Our study population included 280 participants. Only 1 participant required an ED visit or hospitalization because of an adverse event. Of 99 participants who underwent anti-receptor binding domain IgG antibody measurement, 98 had a detectable antibody, with a mean antibody level of 43.0 µg/mL (SD 67) and a median of 22 µg/mL (interquartile range 12-38). In adjusted analyses, older age ( P = 0.028) and antitumor necrosis factor monotherapy compared with immunomodulators alone ( P = 0.005) were associated with a decreased antibody level. Antibody response in patients treated with antitumor necrosis factor combination vs monotherapy was numerically lower but not significant. DISCUSSION: Humoral immune response to COVID-19 immunization in children with IBD was robust, despite a high proportion of this pediatric cohort being treated with immunosuppressive agents. Severe vaccine-related AEs were rare. Overall, these findings provide a high level of reassurance that pediatric patients with IBD respond well and safely to SARS-CoV-2 vaccination.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Enfermedades Inflamatorias del Intestino , Adolescente , Adulto , Niño , Preescolar , Humanos , Anticuerpos , Anticuerpos Antivirales , Vacuna BNT162 , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Inmunidad Humoral , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Necrosis , SARS-CoV-2 , Vacunación
14.
Appl Environ Microbiol ; 89(10): e0060523, 2023 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-37800969

RESUMEN

The long-read amplicon provides a species-level solution for the community. With the improvement of nanopore flowcells, the accuracy of Oxford Nanopore Technologies (ONT) R10.4.1 has been substantially enhanced, with an average of approximately 99%. To evaluate its effectiveness on amplicons, three types of microbiomes were analyzed by 16S ribosomal RNA (hereinafter referred to as "16S") amplicon sequencing using Novaseq, Pacbio sequel II, and Nanopore PromethION platforms (R9.4.1 and R10.4.1) in the current study. We showed the error rate, recall, precision, and bias index in the mock sample. The error rate of ONT R10.4.1 was greatly reduced, with a better recall in the case of the synthetic community. Meanwhile, in different types of environmental samples, ONT R10.4.1 analysis resulted in a composition similar to Pacbio data. We found that classification tools and databases influence ONT data. Based on these results, we conclude that the ONT R10.4.1 16S amplicon can also be used for application in environmental samples. IMPORTANCE The long-read amplicon supplies the community with a species-level solution. Due to the high error rate of nanopore sequencing early on, it has not been frequently used in 16S studies. Oxford Nanopore Technologies (ONT) introduced the R10.4.1 flowcell with Q20+ reagent to achieve more than 99% accuracy as sequencing technology advanced. However, there has been no published study on the performance of commercial PromethION sequencers with R10.4.1 flowcells on 16S sequencing or on the impact of accuracy improvement on taxonomy (R9.4.1 to R10.4.1) using 16S ONT data. In this study, three types of microbiomes were investigated by 16S ribosomal RNA (rRNA) amplicon sequencing using Novaseq, Pacbio sequel II, and Nanopore PromethION platforms (R9.4.1 and R10.4.1). In the mock sample, we displayed the error rate, recall, precision, and bias index. We observed that the error rate in ONT R10.4.1 is significantly lower, especially when deletions are involved. First and foremost, R10.4.1 and Pacific Bioscience platforms reveal a similar microbiome in environmental samples. This study shows that the R10.4.1 full-length 16S rRNA sequences allow for species identification of environmental microbiota.


Asunto(s)
Microbiota , Nanoporos , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN/métodos , Microbiota/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos
15.
Glob Chang Biol ; 29(1): 231-242, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36226978

RESUMEN

Microbial communities play critical roles in fixing carbon from the atmosphere and fixing it in the soils. However, the large-scale variations and drivers of these microbial communities remain poorly understood. Here, we conducted a large-scale survey across China and found that soil autotrophic organisms are critical for explaining CO2 fluxes from the atmosphere to soils. In particular, we showed that large-scale variations in CO2 fixation rates are highly correlated to those in autotrophic bacteria and phototrophic protists. Paddy soils, supporting a larger proportion of obligate bacterial and protist autotrophs, display four-fold of CO2 fixation rates over upland and forest soils. Precipitation and pH, together with key ecological clusters of autotrophic microbes, also played important roles in controlling CO2 fixation. Our work provides a novel quantification on the contribution of terrestrial autotrophic microbes to soil CO2 fixation processes at a large scale, with implications for global carbon regulation under climate change.


Asunto(s)
Dióxido de Carbono , Suelo , Suelo/química , Microbiología del Suelo , Procesos Autotróficos/fisiología , Carbono , Bacterias
16.
Cell Mol Neurobiol ; 43(3): 991-1003, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35678887

RESUMEN

The brain has many connections with various organs. Recent advances have demonstrated the existence of a bidirectional central nervous system (CNS) and intestinal tract, that is, the brain-gut axis. Although studies have suggested that the brain and lung can communicate with each other through many pathways, whether there is a brain-lung axis remains still unknown. Based on previous findings, we put forward a hypothesis: there is a cross-talk between the central nervous system and the lung via neuroanatomical pathway, endocrine pathway, immune pathway, metabolites and microorganism pathway, gas pathway, that is, the brain-lung axis. Beyond the regulation of the physiological state in the body, bi-directional communication between the lung and the brain is associated with a variety of disease states, including lung diseases and CNS diseases. Exploring the brain-lung axis not only helps us to understand the development of the disease from different aspects, but also provides an important target for treatment strategies.


Asunto(s)
Encéfalo , Enfermedades del Sistema Nervioso Central , Humanos , Encéfalo/metabolismo , Sistema Nervioso Central , Intestinos , Enfermedades del Sistema Nervioso Central/metabolismo , Pulmón
17.
Bioorg Med Chem Lett ; 80: 129101, 2023 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-36481449

RESUMEN

In this study, a series of structurally novel N-(benzene sulfonyl) acetamide derivatives were designed, synthesized, and biologically evaluated as COX-2/5-LOX/TRPV1 multitarget inhibitors for anti-inflammatory and analgesic therapy. Among them, 9a and 9b displayed favorable COX-2 (9a IC50 = 0.011 µM, 9b IC50 = 0.023 µM), 5-LOX (9a IC50 = 0.046 µM, 9b IC50 = 0.31 µM) and TRPV1 (9a IC50 = 0.008 µM, 9b IC50 = 0.14 µM) inhibitory activities. The pharmacokinetic (PK) study of 9a in SD rats at the dosage of 10 mg/kg demonstrated a high oral exposure, an acceptable clearance and a favorable bioavailability (Cmax = 5807.18 ± 2657.83 ng/mL, CL = 3.24 ± 1.47 mL/min/kg, F = 96.8 %). Further in vivo efficacy studies illustrated that 9a was capable of ameliorating formalin-induced pain and inhibiting capsaicin-induced ear edema.


Asunto(s)
Analgésicos , Benceno , Ratas , Animales , Ciclooxigenasa 2/metabolismo , Ratas Sprague-Dawley , Analgésicos/farmacología , Analgésicos/uso terapéutico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Inhibidores de la Ciclooxigenasa 2/farmacología , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Amidas/uso terapéutico , Acetamidas/farmacología , Acetamidas/uso terapéutico , Relación Estructura-Actividad , Edema/inducido químicamente , Edema/tratamiento farmacológico , Simulación del Acoplamiento Molecular , Antiinflamatorios no Esteroideos/farmacología , Canales Catiónicos TRPV
18.
Environ Sci Technol ; 57(1): 790-800, 2023 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-36516830

RESUMEN

Widespread antibiotic resistance genes (ARGs) have emerged as a focus of attention for public health. Transformation is essential for ARGs dissemination in soils and associated environments; however, the mechanisms of how soil components contribute to the transformation of ARGs remain elusive. Here we demonstrate that three representative mineral-humic acid (HA) composites exert contrasting influence on the transformation of plasmid-borne ARGs in Bacillus subtilis. Mineral surface-bound HA facilitated transformation in kaolinite and montmorillonite systems, while an inhibitory effect of HA was observed for goethite. The elevated transformation by HA-coated kaolinite was mainly attributed to the enhanced activity of competence-stimulating factor (CSF), while increased transformation by montmorillonite-HA composites was assigned to the weakened adsorption affinity of DNA and enhanced gene expression induced by flagella-driven cell motility. In goethite system, HA played an overriding role in suppressing transformation via alleviation of cell membrane damage. The results obtained offer insights into the divergent mechanisms of humic substances in modulating bacterial transformation by soil minerals. Our findings would help for a better understanding on the fate of ARGs in soil systems and provide potentials for the utilization of soil components, particularly organic matter, to mitigate the spread of ARGs in a range of settings.


Asunto(s)
Sustancias Húmicas , Caolín , Bentonita , Antibacterianos , Minerales , Suelo , Farmacorresistencia Microbiana/genética , Adsorción
19.
Environ Sci Technol ; 57(12): 4905-4914, 2023 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-36917516

RESUMEN

Microbial consortia have opened new avenues for heavy-metal remediation. However, the limited understanding of the overall effect of interspecific interactions on remediation efficacy hinders its application. Here, the effects of multispecies growth and biofilm formation on Cd immobilization were explored from direct and multiple interactions through random combinations of two or three rhizosphere bacteria. In monocultures, Cd stress resulted in an average decrease in planktonic biomass of 26%, but through cooperation, the decrease was attenuated in dual (21%) and triple cultures (13%), possibly involving an increase in surface polysaccharides. More than 65% of the co-cultures exhibited induction of biofilm formation under Cd stress, which further enhanced the role of biofilms in Cd immobilization. Notably, excellent biofilm-forming ability or extensive social induction makes Pseudomonas putida and Brevundimonas diminuta stand out in multispecies biofilm formation and Cd immobilization. These two core species significantly increase the colonization of soil microorganisms on rice roots compared to the control, resulting in a 40% decrease in Cd uptake by rice. Our study enhances the understanding of bacterial interactions under Cd stress and provides a novel strategy for adjusting beneficial soil consortia for heavy-metal remediation.


Asunto(s)
Metales Pesados , Oryza , Contaminantes del Suelo , Cadmio , Bacterias , Suelo , Rizosfera
20.
Environ Sci Technol ; 57(9): 3590-3601, 2023 03 07.
Artículo en Inglés | MEDLINE | ID: mdl-36811608

RESUMEN

Protist predation is a crucial biotic driver modulating bacterial populations and functional traits. Previous studies using pure cultures have demonstrated that bacteria with copper (Cu) resistance exhibited fitness advantages over Cu-sensitive bacteria under the pressure of protist predation. However, the impact of diverse natural communities of protist grazers on bacterial Cu resistance in natural environments remains unknown. Here, we characterized the communities of phagotrophic protists in long-term Cu-contaminated soils and deciphered their potential ecological impacts on bacterial Cu resistance. Long-term field Cu pollution increased the relative abundances of most of the phagotrophic lineages in Cercozoa and Amoebozoa but reduced the relative abundance of Ciliophora. After accounting for soil properties and Cu pollution, phagotrophs were consistently identified as the most important predictor of the Cu-resistant (CuR) bacterial community. Phagotrophs positively contributed to the abundance of a Cu resistance gene (copA) through influencing the cumulative relative abundance of Cu-resistant and -sensitive ecological clusters. Microcosm experiments further confirmed the promotion effect of protist predation on bacterial Cu resistance. Our results indicate that the selection by protist predation can have a strong impact on the CuR bacterial community, which broadens our understanding of the ecological function of soil phagotrophic protists.


Asunto(s)
Cobre , Suelo , Cobre/farmacología , Bacterias/genética , Microbiología del Suelo
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