RESUMEN
Antibodies to the hemagglutinin (HA) and neuraminidase (NA) glycoproteins are the major mediators of protection against influenza virus infection. Here, we report that current influenza vaccines poorly display key NA epitopes and rarely induce NA-reactive B cells. Conversely, influenza virus infection induces NA-reactive B cells at a frequency that approaches (H1N1) or exceeds (H3N2) that of HA-reactive B cells. NA-reactive antibodies display broad binding activity spanning the entire history of influenza A virus circulation in humans, including the original pandemic strains of both H1N1 and H3N2 subtypes. The antibodies robustly inhibit the enzymatic activity of NA, including oseltamivir-resistant variants, and provide robust prophylactic protection, including against avian H5N1 viruses, in vivo. When used therapeutically, NA-reactive antibodies protected mice from lethal influenza virus challenge even 48 hr post infection. These findings strongly suggest that influenza vaccines should be optimized to improve targeting of NA for durable and broad protection against divergent influenza strains.
Asunto(s)
Anticuerpos Monoclonales/inmunología , Gripe Humana/patología , Neuraminidasa/inmunología , Proteínas Virales/inmunología , Animales , Aves , Reacciones Cruzadas , Epítopos/inmunología , Femenino , Células HEK293 , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Subtipo H1N1 del Virus de la Influenza A/enzimología , Subtipo H3N2 del Virus de la Influenza A/enzimología , Subtipo H5N1 del Virus de la Influenza A/inmunología , Subtipo H5N1 del Virus de la Influenza A/patogenicidad , Gripe Humana/inmunología , Ratones , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae/patología , Infecciones por Orthomyxoviridae/prevención & controlRESUMEN
Polyreactivity is the ability of a single antibody to bind to multiple molecularly distinct antigens and is a common feature of antibodies induced upon pathogen exposure. However, little is known about the role of polyreactivity during anti-influenza virus antibody responses. By analyzing more than 500 monoclonal antibodies (mAbs) derived from B cells induced by numerous influenza virus vaccines and infections, we found mAbs targeting conserved neutralizing influenza virus hemagglutinin epitopes were polyreactive. Polyreactive mAbs were preferentially induced by novel viral exposures due to their broad viral binding breadth. Polyreactivity augmented mAb viral binding strength by increasing antibody flexibility, allowing for adaption to imperfectly conserved epitopes. Lastly, we found affinity-matured polyreactive B cells were typically derived from germline polyreactive B cells that were preferentially selected to participate in B cell responses over time. Together, our data reveal that polyreactivity is a beneficial feature of antibodies targeting conserved epitopes.
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Linfocitos B/inmunología , Anticuerpos ampliamente neutralizantes/inmunología , Orthomyxoviridae/inmunología , Anticuerpos Monoclonales/genética , Anticuerpos Monoclonales/inmunología , Afinidad de Anticuerpos , Anticuerpos ampliamente neutralizantes/genética , Reacciones Cruzadas , Epítopos de Linfocito B/inmunología , Genes de Inmunoglobulinas , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Humanos , Vacunas contra la Influenza/inmunología , Gripe Humana/inmunología , Gripe Humana/prevención & control , Gripe Humana/virología , Orthomyxoviridae/clasificación , Dominios Proteicos , Hipermutación Somática de InmunoglobulinaRESUMEN
Enteropathogenic E. coli NleB and related type III effectors catalyze arginine GlcNAcylation of death domain (DD) proteins to block host defense, but the underlying mechanism is unknown. Here we solve crystal structures of NleB alone and in complex with FADD-DD, UDP, and Mn2+ as well as NleB-GlcNAcylated DDs of TRADD and RIPK1. NleB adopts a GT-A fold with a unique helix-pair insertion to hold FADD-DD; the interface contacts explain the selectivity of NleB for certain DDs. The acceptor arginine is fixed into a cleft, in which Glu253 serves as a base to activate the guanidinium. Analyses of the enzyme-substrate complex and the product structures reveal an inverting sugar-transfer reaction and a detailed catalytic mechanism. These structural insights are validated by mutagenesis analyses of NleB-mediated GlcNAcylation in vitro and its function in mouse infection. Our study builds a structural framework for understanding of NleB-catalyzed arginine GlcNAcylation of host death domain.
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Escherichia coli Enteropatógena/genética , Proteínas de Escherichia coli/química , Interacciones Huésped-Patógeno/genética , Conformación Proteica , Factores de Virulencia/química , Animales , Apoptosis/genética , Arginina/química , Arginina/genética , Coenzima A Ligasas/química , Coenzima A Ligasas/genética , Cristalografía por Rayos X , Dominio de Muerte/genética , Escherichia coli Enteropatógena/patogenicidad , Proteínas de Escherichia coli/genética , Guanidina/química , Humanos , Manganeso/química , Ratones , Mutagénesis , Proteína de Dominio de Muerte Asociada a Receptor de TNF/química , Proteína de Dominio de Muerte Asociada a Receptor de TNF/genética , Factores de Virulencia/genéticaRESUMEN
Human DNA topoisomerase 1 (Top1) is a crucial enzyme responsible for alleviating torsional stress on DNA during transcription and replication, thereby maintaining genome stability. Previous researches had found that non-working Top1 interacted extensively with chromosomal DNA in human cells. However, the reason for its retention on chromosomal DNA remained unclear. In this study, we discovered a close association between Top1 and chromosomal DNA, specifically linked to the presence of G-quadruplex (G4) structures. G4 structures, formed during transcription, trap Top1 and hinder its ability to relax neighboring DNAs. Disruption of the Top1-G4 interaction using G4 ligand relieved the inhibitory effect of G4 on Top1 activity, resulting in a further reduction of R-loop levels in cells. Additionally, the activation of Top1 through the use of a G4 ligand enhanced the toxicity of Top1 inhibitors towards cancer cells. Our study uncovers a negative regulation mechanism of human Top1 and highlights a novel pathway for activating Top1.
Asunto(s)
ADN-Topoisomerasas de Tipo I , G-Cuádruplex , Transcripción Genética , Humanos , ADN/química , Replicación del ADN , ADN-Topoisomerasas de Tipo I/metabolismo , Ligandos , Inhibidores de Topoisomerasa I/farmacologíaRESUMEN
Enterovirus A71 (EV-A71) infection is a major cause of severe hand, foot and mouth disease (HFMD) in young children. The characteristics of EV-A71 neutralizing antibodies in HFMD patients are not well understood. In this study, we identified and cloned EV-A71-neutralizing antibodies by single cell RNA and B cell receptor sequencing of peripheral blood mononuclear cells. From 145 plasmablasts, we identified two IgG1 monoclonal antibodies (mAbs) and six IgM mAbs that neutralized EV-A71. Four of the IgM mAbs harbor germline variable sequences and neutralize EV-A71 potently. Two genetically similar IgM antibodies from two patients have recurrent heavy chain variable domain gene usage and similar complementarity-determining region 3 sequences. We mapped the residues of EV-A71 critical for neutralization through selection of virus variants resistant to antibody neutralization in the presence of neutralizing mAbs. The residues critical for neutralization are conserved among EV-A71 genotypes. Epitopes for the two genetically similar antibodies overlap with the SCARB2 binding site of EV-A71. We used escape variants to measure the epitope-specific antibody response in acute phase serum samples from EV-A71 infected HFMD patients. We found that these epitopes are immunogenic and contributed to the neutralizing antibody response against the virus. Our findings advance understanding of antibody response to EV-A71 infection in young children and have translational potential: the IgM mAbs could potentially be used for prevention or treatment of EV-A71 infections.
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Enterovirus Humano A , Infecciones por Enterovirus , Enterovirus , Enfermedad de Boca, Mano y Pie , Niño , Humanos , Preescolar , Enterovirus/genética , Enterovirus Humano A/genética , Leucocitos Mononucleares , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Epítopos , Inmunoglobulina M , Anticuerpos Monoclonales , Antígenos Virales/genéticaRESUMEN
SARS-CoV Spike (S) protein shares considerable homology with SARS-CoV-2 S, especially in the conserved S2 subunit (S2). S protein mediates coronavirus receptor binding and membrane fusion, and the latter activity can greatly influence coronavirus infection. We observed that SARS-CoV S is less effective in inducing membrane fusion compared with SARS-CoV-2 S. We identify that S813T mutation is sufficient in S2 interfering with the cleavage of SARS-CoV-2 S by TMPRSS2, reducing spike fusogenicity and pseudoparticle entry. Conversely, the mutation of T813S in SARS-CoV S increased fusion ability and viral replication. Our data suggested that residue 813 in the S was critical for the proteolytic activation, and the change from threonine to serine at 813 position might be an evolutionary feature adopted by SARS-2-related viruses. This finding deepened the understanding of Spike fusogenicity and could provide a new perspective for exploring Sarbecovirus' evolution.
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COVID-19 , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo , Humanos , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/genética , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Proteolisis , Replicación Viral , Glicoproteína de la Espiga del Coronavirus/metabolismo , Internalización del Virus , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismoRESUMEN
Multicomponent metallic nanomaterials with unconventional phases show great prospects in electrochemical energy storage and conversion, owing to unique crystal structures and abundant structural effects. In this review, we emphasize the progress in the strain and surface engineering of these novel nanomaterials. We start with a brief introduction of the structural configurations of these materials, based on the interaction types between the components. Next, the fundamentals of strain, strain effect in relevant metallic nanomaterials with unconventional phases, and their formation mechanisms are discussed. Then the progress in surface engineering of these multicomponent metallic nanomaterials is demonstrated from the aspects of morphology control, crystallinity control, surface modification, and surface reconstruction. Moreover, the applications of the strain- and surface-engineered unconventional nanomaterials mainly in electrocatalysis are also introduced, where in addition to the catalytic performance, the structure-performance correlations are highlighted. Finally, the challenges and opportunities in this promising field are prospected.
RESUMEN
Amorphous nanomaterials have drawn extensive attention owing to their unique features, while amorphization on noble metal nanomaterials still remains formidably challenging. Herein, we demonstrate a universal strategy to synthesize amorphous Pd-based nanomaterials from unary to quinary metals through the introduction of phosphorus (P). The amorphous Pd-based nanoparticles (NPs) exhibit generally promoted oxygen reduction reaction (ORR) activity and durability compared with their crystalline counterparts. Significantly, the quinary P-PdCuNiInSn NPs, benefiting from the amorphous structure and multimetallic component effect, exhibit mass activities as high as 1.04 A mgPd-1 and negligible activity decays of 1.8% among the stability tests, which are much better than values for original Pd NPs (0.134 A mgPd-1 and 28.4%). Experimental and theoretical analyses collectively reveal that the synergy of P-induced amorphization and the expansion of metallic components can considerably lower the free energy changes in the rate-determined step, thereby explaining the positive correlation with the catalytic activity.
RESUMEN
Osteoarthritis (OA) is a chronic degenerative joint disease that affects worldwide. Oxidative stress plays a critical role in the chronic inflammation and OA progression. Scavenging overproduced reactive oxygen species (ROS) could be rational strategy for OA treatment. Bilirubin (BR) is a potent endogenous antioxidant that can scavenge various ROS and also exhibit anti-inflammatory effects. However, whether BR could exert protection on chondrocytes for OA treatment has not yet been elucidated. Here, chondrocytes were exposed to hydrogen peroxide with or without BR treatment. The cell viability was assessed, and the intracellular ROS, inflammation cytokines were monitored to indicate the state of chondrocytes. In addition, BR was also tested on LPS-treated Raw264.7 cells to test the anti-inflammation property. An in vitro bimimic OA microenvironment was constructed by LPS-treated Raw264.7 and chondrocytes, and BR also exert certain protection for chondrocytes by activating Nrf2/HO-1 pathway and suppressing NF-κB signalling. An ACLT-induced OA model was constructed to test the in vivo therapeutic efficacy of BR. Compared to the clinical used HA, BR significantly reduced cartilage degeneration and delayed OA progression. Overall, our data shows that BR has a protective effect on chondrocytes and can delay OA progression caused by oxidative stress.
Asunto(s)
FN-kappa B , Osteoartritis , Humanos , FN-kappa B/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Bilirrubina/farmacología , Lipopolisacáridos/farmacología , Osteoartritis/tratamiento farmacológico , Osteoartritis/metabolismo , Inflamación/tratamiento farmacológico , Condrocitos/metabolismo , Interleucina-1beta/farmacologíaRESUMEN
Hyperactivation of the cyclic-GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signalling pathway has been shown to be associated with the development of a variety of inflammatory diseases, and the discovery of an inhibitor of the cGAS-STING signalling pathway holds great promise in the therapeutic interventions. Epimedium flavonoid (EF), a major active ingredient isolated from the medicinal plant Epimedium, has been reported to have good anti-inflammatory activity, but its exact mechanism of action remains unclear. In the present study, we found that EF in mouse bone marrow-derived macrophages (BMDMs), THP-1 (Tohoku Hospital Pediatrics-1) as well as in human peripheral blood mononuclear cells (hPBMC) inhibited the activation of the cGAS-STING signalling pathway, which subsequently led to a decrease in the expression of type I interferon (IFN-ß, CXCL10 and ISG15) and pro-inflammatory cytokines (IL-6 and TNF-α). Mechanistically, EF does not affect STING oligomerization, but inhibits the formation of functional STING signalosome by attenuating the interaction of interferon regulatory factor 3 (IRF3) with STING and TANK-binding kinase 1 (TBK1). Importantly, in vivo experiments, EF has shown promising therapeutic effects on inflammatory diseases mediated by the cGAS-STING pathway, which include the agonist model induced by DMXAA stimulation, the autoimmune inflammatory disease model induced by three prime repair exonuclease 1 (Trex1) deficiency, and the non-alcoholic steatohepatitis (NASH) model induced by a pathogenic amino acid and choline deficiency diet (MCD). To summarize, our study suggests that EF is a potent potential inhibitor component of the cGAS-STING signalling pathway for the treatment of inflammatory diseases mediated by the cGAS-STING signalling pathway.
Asunto(s)
Epimedium , Flavonoides , Proteínas de la Membrana , Nucleotidiltransferasas , Transducción de Señal , Nucleotidiltransferasas/metabolismo , Proteínas de la Membrana/metabolismo , Animales , Transducción de Señal/efectos de los fármacos , Humanos , Ratones , Flavonoides/farmacología , Epimedium/química , Factor 3 Regulador del Interferón/metabolismo , Macrófagos/metabolismo , Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Ratones Endogámicos C57BL , Citocinas/metabolismo , Células THP-1 , Proteínas Serina-Treonina Quinasas/metabolismo , Antiinflamatorios/farmacología , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/efectos de los fármacosRESUMEN
Long non-coding RNAs (lncRNAs) has become a vital regulator in the pathogenesis of osteoporosis (OP). This study aimed to investigate the role of lncRNA DLEU2 in the development of proliferation and apoptosis of human bone marrow mesenchymal stem cells (hBMSCs). High-throughput sequencing in bone tissues from 3 pairs of healthy donors and OP patients was used to search for differential lncRNAs. The expression of DLEU2 was also verified in bone tissues. The hBMSCs were transfected with DLEU2 ASO. Cell viability was detected suing MTT. Cell proliferation was determined using colony formation and EdU assays. Cell cycle and apoptosis was detected using flow cytometry. RIP, RNA pulldown, and Co-IP assays were carried out to verify the interaction between protein and protein/RNA. The binding sites between GFI1 and the promoter of DLEU2 was verified using ChIP and luciferase assays. DLEU2 expression was down-regulated in OP patients. Knockdown of DLEU2 expression significantly inhibited proliferation and promoted apoptosis of hBMSCs. Moreover, DLEU2 could interact with EZH2 to induce the activation of GFI1. Additionally, GFI1 transcriptionally activated DLEU2. Taken together, DLEU2/EZH2/GFI1 axis suppressed proliferation and enhanced hBMSC apoptosis. This may provide novel strategy for OP.
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Proteínas de Unión al ADN , Proteína Potenciadora del Homólogo Zeste 2 , Células Madre Mesenquimatosas , MicroARNs , ARN Largo no Codificante , Factores de Transcripción , Humanos , Apoptosis/genética , Proliferación Celular/genética , Proteínas de Unión al ADN/metabolismo , Proteína Potenciadora del Homólogo Zeste 2/genética , MicroARNs/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Factores de Transcripción/metabolismoRESUMEN
Vascular intimal injury initiates various cardiovascular disease processes. Exposure to subendothelial collagen can cause platelet activation, leading to collagen-activated platelet-derived microvesicles (aPMVs) secretion. In addition, vascular smooth muscle cells (VSMCs) exposed to large amounts of aPMVs undergo abnormal energy metabolism; they proliferate excessively and migrate after the loss of endothelium, eventually contributing to neointimal hyperplasia. However, the roles of aPMVs in VSMC energy metabolism are still unknown. Our carotid artery intimal injury model indicated that platelets adhered to injured blood vessels. In vitro, phosphorylated Pka (cAMP-dependent protein kinase) content was increased in aPMVs. We also found that aPMVs significantly reduced VSMC glycolysis and increased oxidative phosphorylation, and promoted VSMC migration and proliferation by upregulating phosphorylated PRKAA (α catalytic subunit of AMP-activated protein kinase) and phosphorylated FoxO1. Compound C, an inhibitor of PRKAA, effectively reversed the enhancement of cellular function and energy metabolism triggered by aPMVs in vitro and neointimal formation in vivo. We show that aPMVs can affect VSMC energy metabolism through the Pka-PRKAA-FoxO1 signaling pathway and this ultimately affects VSMC function, indicating that the shift in VSMC metabolic phenotype by aPMVs can be considered a potential target for the inhibition of hyperplasia. This provides a new perspective for regulating the abnormal activity of VSMCs after injury.
Asunto(s)
Traumatismos de las Arterias Carótidas , Músculo Liso Vascular , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Plaquetas/metabolismo , Traumatismos de las Arterias Carótidas/genética , Traumatismos de las Arterias Carótidas/metabolismo , Movimiento Celular , Proliferación Celular , Células Cultivadas , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Modelos Animales de Enfermedad , Metabolismo Energético , Humanos , Hiperplasia/complicaciones , Hiperplasia/metabolismo , Hiperplasia/patología , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Neointima/complicaciones , Neointima/metabolismo , Neointima/patologíaRESUMEN
Addressing the challenge of lighting stability in perovskite white light emitting diodes (WLEDs) is crucial for their commercial viability. CsPbX3 (X = Cl, Br, I, or mixed) nanocrystals (NCs) are promising for next-generation lighting due to their superior optical and electronic properties. However, the inherent soft material structure of CsPbX3 NCs is particularly susceptible to the elevated temperatures associated with prolonged WLED operation. Additionally, these NCs face stability challenges in high humidity environments, leading to reduced lighting performance. This study introduces a two-step dual encapsulation method, resulting in CsPbBr3@SiO2/Al2SiO5 composite fibers (CFs) with enhanced optical stability under extreme conditions. In testing, WLEDs incorporating these CFs, even under prolonged operation at high power (100 mA for 9 h), maintain consistent electroluminescence (EL) intensity and optoelectronic parameters, with surface temperatures reaching 84.2 °C. Crucially, when subjected to 85 °C and 85% relative humidity for 200 h, the WLEDs preserve 97% of their initial fluorescence efficiency. These findings underscore the efficacy of the dual encapsulation strategy in significantly improving perovskite material stability, marking a significant step toward their commercial application in optoelectronic lighting.
RESUMEN
Antibodies specifically bind to antigens and are an essential part of the immune system. Hence, antibodies are powerful tools in research and diagnostics. High-throughput sequencing technologies have promoted comprehensive profiling of the immune repertoire, which has resulted in large amounts of antibody sequences that remain to be further analyzed. In this study, antibodies were downloaded from IMGT/LIGM-DB and Sequence Read Archive databases. Contributing features from antibody heavy chains were formulated as numerical inputs and fed into an ensemble machine learning classifier to classify the antigen specificity of six classes of antibodies, namely anti-HIV-1, anti-influenza virus, anti-pneumococcal polysaccharide, anti-citrullinated protein, anti-tetanus toxoid and anti-hepatitis B virus. The classifier was validated using cross-validation and a testing dataset. The ensemble classifier achieved a macro-average area under the receiver operating characteristic curve (AUC) of 0.9246 from the 10-fold cross-validation, and 0.9264 for the testing dataset. Among the contributing features, the contribution of the complementarity-determining regions was 53.1% and that of framework regions was 46.9%, and the amino acid mutation rates occupied the first and second ranks among the top five contributing features. The classifier and insights provided in this study could promote the mechanistic study, isolation and utilization of potential therapeutic antibodies.
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Secuencia de Aminoácidos , Anticuerpos/química , Aprendizaje Automático , Especificidad de Anticuerpos , Regiones Determinantes de Complementariedad , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Curva ROCRESUMEN
While micronutrients are crucial for immune function, their impact on humoral responses to inactivated COVID-19 vaccination remains unclear. We investigated the associations between seven key micronutrients and antibody responses in 44 healthy adults with two doses of an inactivated COVID-19 vaccine. Blood samples were collected pre-vaccination and 28 days post-booster. We measured circulating minerals (iron, zinc, copper, and selenium) and vitamins (A, D, and E) concentrations alongside antibody responses and assessed their associations using linear regression analyses. Our analysis revealed inverse associations between blood iron and zinc concentrations and anti-SARS-CoV-2 IgM antibody binding affinity (AUC for iron: ß = -258.21, p < 0.0001; zinc: ß = -17.25, p = 0.0004). Notably, antibody quality presented complex relationships. Blood selenium was positively associated (ß = 18.61, p = 0.0030), while copper/selenium ratio was inversely associated (ß = -1.36, p = 0.0055) with the neutralizing ability against SARS-CoV-2 virus at a 1:10 plasma dilution. There was no significant association between circulating micronutrient concentrations and anti-SARS-CoV-2 IgG binding affinity. These findings suggest that circulating iron, zinc, and selenium concentrations and copper/selenium ratio, may serve as potential biomarkers for both quantity (binding affinity) and quality (neutralization) of humoral responses after inactivated COVID-19 vaccination. Furthermore, they hint at the potential of pre-vaccination dietary interventions, such as selenium supplementation, to improve vaccine efficacy. However, larger, diverse studies are needed to validate these findings. This research advances the understanding of the impact of micronutrients on vaccine response, offering the potential for personalized vaccination strategies.
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COVID-19 , Selenio , Oligoelementos , Adulto , Humanos , Micronutrientes , Vacunas contra la COVID-19 , Cobre , COVID-19/prevención & control , SARS-CoV-2 , Zinc , Hierro , Vacunación , Anticuerpos Antivirales , Anticuerpos NeutralizantesRESUMEN
A novel Gram-stain-negative strain, designated JM10B15T, was isolated from pond water for Litopenaeus vannamei collected from Jiangmen City, Guangdong province, south PR China. Cells of the strain were aerobic, rod-shaped, and motile by lateral flagella. JM10B15T could grow at 15-40â°C, pH 6.0-9.5, and in 0-3.0â% NaCl, with optimal growth at 25-35â°C, pH 7.5-8.5, and in 0â% NaCl, respectively. Furthermore, this strain grew well on Reasoner's 2A agar but not on nutrient broth agar or Luria-Bertani agar. JM10B15T was a denitrifying bacterium capable of removing nitrites and nitrates, and three key functional genes, nasA, nirS, and nosZ, were identified in its genome. The results of phylogenetic analyses based on the 16S rRNA gene and genome sequences indicated that JM10B15T belonged to the genus Gemmobacter. JM10B15T showed the highest 16S rRNA sequence similarity to Gemmobacter lutimaris YJ-T1-11T (98.8â%), followed by Gemmobacter aquatilis IFAM 1031T (98.6â%) and Gemmobacter serpentinus HB-1T (98.1â%). The average nucleotide identity and digital DNA-DNA hybridization values between JM10B15T and the other type strains of genus Gemmobacter were 78.1-82.1â% and 18.4-22.1â%, respectively. The major fatty acids of strain JM10B15T were summed feature 8 (C18â:â1 ω6c and/or C18â:â1 ω7c) and C18â:â1 ω7c 11-methyl. In addition, the major respiratory quinone of this novel strain was Q-10, and the predominant polar lipids were phosphatidylglycerol, phosphatidylethanolamine, four unidentified phospholipids, three unidentified lipids, and an unidentified aminophospholipid. Results of analyses of the phylogenetic, genomic, physiological, and biochemical characteristics indicated that JM10B15T represents a novel species of the genus Gemmobacter, for which the name Gemmobacter denitrificans sp. nov. is proposed. The type strain is JM10B15T (=GDMCC 1.4148T=KCTC 8140T).
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Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano , Desnitrificación , Ácidos Grasos , Hibridación de Ácido Nucleico , Penaeidae , Filogenia , Estanques , ARN Ribosómico 16S , Análisis de Secuencia de ADN , ARN Ribosómico 16S/genética , Estanques/microbiología , ADN Bacteriano/genética , China , Animales , Penaeidae/microbiología , Fosfolípidos , Microbiología del Agua , Nitratos/metabolismo , Ubiquinona , Nitritos/metabolismoRESUMEN
A novel plant-beneficial bacterium strain, designated as JGH33T, which inhibited Peronophythora litchii sporangia germination, was isolated on Reasoner's 2A medium from a litchi rhizosphere soil sample collected in Gaozhou City, Guangdong Province, PR China. Cells of strain JGH33T were Gram-stain-positive, aerobic, non-motile, bent rods. The strain grew optimally at 30-37â°C and pH 6.0-8.0. Sequence similarity analysis based on 16S rRNA genes indicated that strain JGH33T exhibited highest sequence similarity to Sinomonas albida LC13T (99.2â%). The genomic DNA G+C content of the isolate was 69.1âmol%. The genome of JGH33T was 4.7 Mbp in size with the average nucleotide identity value of 83.45â% to the most related reference strains, which is lower than the species delineation threshold of 95â%. The digital DNA-DNA hybridization of the isolate resulted in a relatedness value of 24.9â% with its closest neighbour. The predominant respiratory quinone of JGH33T was MK-9(H2). The major fatty acids were C15â:â0 anteiso (43.4â%), C16â:â0 iso (19.1â%) and C17â:â0 anteiso (19.3â%), and the featured component was C18â:â3 ω6c (1.01â%). The polar lipid composition of strain JGH33T included diphosphatidylglycerol, phosphatidylglycerol, dimannosylglyceride, phosphatidylinositol and glycolipids. On the basis of polyphasic taxonomy analyses data, strain JGH33T represents a novel species of the genus Sinomonas, for which the name Sinomonas terricola sp. nov. is proposed, with JGH33T (=JCM 35868T=GDMCC 1.3730T) as the type strain.
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Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano , Ácidos Grasos , Litchi , Hibridación de Ácido Nucleico , Filogenia , ARN Ribosómico 16S , Rizosfera , Análisis de Secuencia de ADN , Microbiología del Suelo , Vitamina K 2 , China , ARN Ribosómico 16S/genética , Ácidos Grasos/análisis , ADN Bacteriano/genética , Litchi/microbiología , Vitamina K 2/análogos & derivados , Vitamina K 2/análisis , Fosfolípidos/análisisRESUMEN
Disclosed herein is a rhodium(III)-catalyzed direct heteroarylation reaction between unactivated aliphatic C(sp3)-H bonds in 2-alkylpyridines and heteroaryl organoboron reagents. This catalytic protocol is compatible with various heterocyclic boronates containing ortho- and meta-pyridine, pyrazoles, furan, and quinoline with strong coordination capability. The achievement of this methodology provides an efficient route to build new C(sp3)-heteroaryl bonds.
RESUMEN
BACKGROUND: Both atrial fibrillation (AF) and heart failure (HF) are common cardiovascular diseases. If the two exist together, the risk of stroke, hospitalization for HF and all-cause death is increased. Currently, research on left atrial appendage closure (LAAC) in patients with AF and HF is limited and controversial. This study was designed to investigate the safety and effectiveness of LAAC in AF patients with different types of HF. METHODS: Patients with non-valvular atrial fibrillation (NVAF) and HF who underwent LAAC in the First Affiliated Hospital of Army Medical University from August 2014 to July 2021 were enrolled. According to left ventricular ejection fraction (LVEF), the study divided into HF with reduced ejection fraction (LVEF < 50%, HFrEF) group and HF with preserved ejection fraction (LVEF ≥ 50%, HFpEF) group. The data we collected from patients included: gender, age, comorbid diseases, CHA2DS2-VASc score, HAS-BLED score, NT-proBNP level, residual shunt, cardiac catheterization results, occluder size, postoperative medication regimen, transthoracic echocardiography (TTE) results and transesophageal echocardiography (TEE) results, etc. Patients were followed up for stroke, bleeding, device related thrombus (DRT), pericardial tamponade, hospitalization for HF, and all-cause death within 2 years after surgery. Statistical methods were used to compare the differences in clinical outcome of LAAC in AF patients with different types of HF. RESULTS: Overall, 288 NVAF patients with HF were enrolled in this study, including 142 males and 146 females. There were 74 patients in the HFrEF group and 214 patients in the HFpEF group. All patients successfully underwent LAAC. The CHA2DS2-VASc score and HAS-BLED score of HFrEF group were lower than those of HFpEF group. A total of 288 LAAC devices were implanted. The average diameter of the occluders was 27.2 ± 3.5 mm in the HFrEF group and 26.8 ± 3.3 mm in the HFpEF group, and there was no statistical difference between the two groups (P = 0.470). Also, there was no statistically significant difference in the occurrence of residual shunts between the two groups as detected by TEE after surgery (P = 0.341). LVEF was significantly higher in HFrEF group at 3 days, 3 months and 1 year after operation than before (P < 0.001). At 45-60 days after surgery, we found DRT in 9 patients and there were 4 patients (5.4%) in HFrEF group and 5 patients (2.3%) in HFpEF group, with no significant difference between the two groups (P = 0.357). One patient with DRT had stroke. The incidence of stroke was 11.1% in patients with DRT and 0.7% in patients without DRT (P = 0.670). There was one case of postoperative pericardial tamponade, which was improved by pericardiocentesis at 24 h after surgery in the HFpEF group, and there was no significant difference between the two groups (P = 1.000). During a mean follow-up period of 49.7 ± 22.4 months, there were no significant differences in the incidence of stroke, bleeding, DRT and HF exacerbation between the two groups. We found a statistical difference in the improvement of HF between HFrEF group and HFpEF group (P < 0.05). CONCLUSIONS: LAAC is safe and effective in AF patients with different types of HF. The improvement of cardiac function after LAAC is more pronounced in HFrEF group than in HFpEF group.
Asunto(s)
Fibrilación Atrial , Función del Atrio Izquierdo , Insuficiencia Cardíaca , Cierre del Apéndice Auricular Izquierdo , Accidente Cerebrovascular , Función Ventricular Izquierda , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Apéndice Atrial/diagnóstico por imagen , Apéndice Atrial/fisiopatología , Apéndice Atrial/cirugía , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/cirugía , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/cirugía , Cierre del Apéndice Auricular Izquierdo/efectos adversos , Recuperación de la Función , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Volumen Sistólico , Factores de Tiempo , Resultado del TratamientoRESUMEN
Neointimal hyperplasia is a pathological vascular remodeling caused by abnormal proliferation and migration of subintimal vascular smooth muscle cells (VSMCs) following intimal injury. There is increasing evidence that tRNA-derived small RNA (tsRNA) plays an important role in vascular remodeling. The purpose of this study is to search for tsRNAs signature of neointima formation and to explore their potential functions. The balloon injury model of rat common carotid artery was replicated to induce intimal hyperplasia, and the differentially expressed tsRNAs (DE-tsRNAs) in arteries with intimal hyperplasia were screened by small RNA sequencing and tsRNA library. A total of 24 DE-tsRNAs were found in the vessels with intimal hyperplasia by small RNA sequencing. In vitro, tRF-Glu-CTC inhibited the expression of fibromodulin (FMOD) in VSMCs, which is a negative modulator of TGF-ß1 activity. tRF-Glu-CTC also increased VSMC proliferation and migration. In vivo experiments showed that inhibition of tRF-Glu-CTC expression after balloon injury of rat carotid artery can reduce the neointimal area. In conclusion, tRF-Glu-CTC expression is increased after vascular injury and inhibits FMOD expression in VSMCs, which influences neointima formation. On the other hand, reducing the expression of tRF-Glu-CTC after vascular injury may be a potential approach to prevent vascular stenosis.