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1.
J Biol Chem ; 299(7): 104844, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37209818

RESUMO

Cytoplasmic stress granules (SGs) are generally triggered by stress-induced translation arrest for storing mRNAs. Recently, it has been shown that SGs are regulated by different stimulators including viral infection, which is involved in the antiviral activity of host cells to limit viral propagation. To survive, several viruses have been reported to execute various strategies, such as modulating SG formation, to create optimal surroundings for viral replication. African swine fever virus (ASFV) is one of the most notorious pathogens in the global pig industry. However, the interplay between ASFV infection and SG formation remains largely unknown. In this study, we found that ASFV infection inhibited SG formation. Through SG inhibitory screening, we found that several ASFV-encoded proteins are involved in inhibition of SG formation. Among them, an ASFV S273R protein (pS273R), the only cysteine protease encoded by the ASFV genome, significantly affected SG formation. ASFV pS273R interacted with G3BP1 (Ras-GTPase-activating protein [SH3 domain] binding protein 1), a vital nucleating protein of SG formation. Furthermore, we found that ASFV pS273R cleaved G3BP1 at the G140-F141 to produce two fragments (G3BP1-N1-140 and G3BP1-C141-456). Interestingly, both the pS273R-cleaved fragments of G3BP1 lost the ability to induce SG formation and antiviral activity. Taken together, our finding reveals that the proteolytic cleavage of G3BP1 by ASFV pS273R is a novel mechanism by which ASFV counteracts host stress and innate antiviral responses.


Assuntos
Vírus da Febre Suína Africana , Grânulos de Estresse , Proteínas Virais , Animais , Febre Suína Africana/metabolismo , Febre Suína Africana/virologia , Vírus da Febre Suína Africana/enzimologia , Vírus da Febre Suína Africana/genética , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Grânulos de Estresse/metabolismo , Suínos , Replicação Viral/fisiologia , Chlorocebus aethiops , Humanos , Células HEK293 , Células Cultivadas , Macrófagos Alveolares/virologia , Proteínas Virais/metabolismo , Proteólise
2.
Plant J ; 114(1): 176-192, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36721978

RESUMO

The supply of boron (B) alleviates the toxic effects of aluminum (Al) on root growth; however, the mechanistic basis of this process remains elusive. This study filled this knowledge gap, demonstrating that boron modifies auxin distribution and transport in Al-exposed Arabidopsis roots. In B-deprived roots, treatment with Al induced an increase in auxin content in the root apical meristem zone (MZ) and transition zone (TZ), whereas in the elongation zone (EZ) the auxin content was decreased beyond the level required for adequate growth. These distribution patterns are explained by the fact that basipetal auxin transport from the TZ to the EZ was disrupted by Al-inhibited PIN-FORMED 2 (PIN2) endocytosis. Experiments involving the modulation of protein biosynthesis by cycloheximide (CHX) and transcriptional regulation by cordycepin (COR) demonstrated that the Al-induced increase of PIN2 membrane proteins was dependent upon the inhibition of PIN2 endocytosis, rather than on the transcriptional regulation of the PIN2 gene. Experiments reporting on the profiling of Al3+ and PIN2 proteins revealed that the inhibition of endocytosis of PIN2 proteins was the result of Al-induced limitation of the fluidity of the plasma membrane. The supply of B mediated the turnover of PIN2 endosomes conjugated with indole-3-acetic acid (IAA), and thus restored the Al-induced inhibition of IAA transport through the TZ to the EZ. Overall, the reported results demonstrate that boron supply mediates PIN2 endosome-based auxin transport to alleviate Al toxicity in plant roots.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/metabolismo , Alumínio/toxicidade , Alumínio/metabolismo , Boro/metabolismo , Proteína 1 de Ligação a Repetições Teloméricas/metabolismo , Raízes de Plantas/metabolismo , Ácidos Indolacéticos/metabolismo , Arabidopsis/metabolismo
3.
Plant J ; 115(5): 1357-1376, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37235684

RESUMO

The mechanistic basis by which boron (B) deprivation inhibits root growth via the mediation of root apical auxin transport and distribution remains elusive. This study showed that B deprivation repressed root growth of wild-type Arabidopsis seedlings, which was related to higher auxin accumulation (observed with DII-VENUS and DR5-GFP lines) in B-deprived roots. Boron deprivation elevated the auxin content in the root apex, coinciding with upregulation of the expression levels of auxin biosynthesis-related genes (TAA1, YUC3, YUC9, and NIT1) in shoots, but not in root apices. Phenotyping experiments using auxin transport-related mutants revealed that the PIN2/3/4 carriers are involved in root growth inhibition caused by B deprivation. B deprivation not only upregulated the transcriptional levels of PIN2/3/4, but also restrained the endocytosis of PIN2/3/4 carriers (observed with PIN-Dendra2 lines), resulting in elevated protein levels of PIN2/3/4 in the plasma membrane. Overall, these results suggest that B deprivation not only enhances auxin biosynthesis in shoots by elevating the expression levels of auxin biosynthesis-related genes but also promotes the polar auxin transport from shoots to roots by upregulating the gene expression levels of PIN2/3/4, as well as restraining the endocytosis of PIN2/3/4 carriers, ultimately resulting in auxin accumulation in root apices and root growth inhibition.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Ácidos Indolacéticos/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Boro/metabolismo , Raízes de Plantas/metabolismo
4.
Small ; 20(14): e2306295, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37992255

RESUMO

Dual-atom catalysts exhibit higher reactivity and selectivity than the single-atom catalysts. The pyrolysis of bimetal salt precursors is the most typical method for synthesizing dual-atomic catalysts; however, the finiteness of bimetal salts limits the variety of dual-atomic catalysts. In this study, a confined synthesis strategy for synthesizing dual-atomic catalysts is developed. Owing to the in situ synthesis of zeolitic imidazolate frameworks in the pores of covalent organic frameworks (COFs), the migration and aggregation of metal atoms are suppressed adequately during the pyrolysis process. The resultant catalyst contains abundant Zn─Co dual atomic sites with 2.8 wt.% Zn and 0.5 wt.% Co. The catalyst exhibits high reactivity toward oxygen reduction reaction with a half-wave potential of 0.86 V, which is superior to that of the commercial Pt/C catalyst. Theoretical calculations reveal that the Zn atoms in the Zn─Co dual atomic sites promote the formation of intermediate OOH*, and thus contribute to high catalytic performance. This study provides new insights into the design of dual-atom catalysts using COFs.

5.
Small ; : e2403655, 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38881262

RESUMO

Developing advanced functional carbon materials is essential for electrocatalysis, caused by their vast merits for boosting many key energy conversion reactions. Herein, the covalent organic frameworks (COFs) is utilized on metal-organic frameworks (MOFs) as the template, under the controllable metal atoms thermal migration process successfully in situ constructs Pd-Co alloy nanoparticles on hollow cubic graphene. The electrocatalytic oxygen reduction reaction (ORR) evaluation showed excellent performances with a half-wave potential of 0.866 V, and a limited current density of 4.975 mA cm-2, that superior to the commercial Pt/C and Co nanoparticles. The contrast experiments and X-ray absorption spectrum demonstrated the aggregated electrons at highly dispersed Pd atoms on Co nanoparticle that promoted the main activities. This work not only enlightens the novel carbon materials designing strategies but also suggests heterogeneous electrocatalysis.

6.
Small ; : e2404192, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39004849

RESUMO

The tunable pore walls and skeletons render covalent organic frameworks (COFs) as promising absorbents for gold (Au) ion. However, most of these COFs suffered from low surface areas hindering binding sites exposed and weak binding interaction resulting in sluggish kinetic performance. In this study, COFs have been constructed with synergistic linker and linkage for high-efficiency Au capture. The designed COFs (PYTA-PZDH-COF and PYTA-BPDH-COF) with pyrazine or bipyridine as linkers showed high surface areas of 1692 and 2076 m2 g‒1, providing high exposed surface areas for Au capture. In addition, the Lewis basic nitrogen atoms from the linkers and linkages are easily hydronium, which enabled to fast trap Au via coulomb force. The PYTA-PZDH-COF and PYTA-BPDH-COF showed maximum Au capture capacities of 2314 and 1810 mg g-1, higher than other reported COFs. More importantly, PYTA-PZDH-COF are capable of rapid adsorption kinetics with achieving 95% of maximum binding capacity in 10 min. The theoretical calculation revealed that the nitrogen atoms in linkers and linkages from both COFs are simultaneously hydronium, and then the protonated PYTA-PZDH-COF are more easily binding the AuCl4 ‒, further accelerating the binding process. This study gives the a new insight to design COFs for ion capture.

7.
J Virol ; 97(7): e0061623, 2023 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-37382521

RESUMO

African swine fever (ASF) is an acute and hemorrhagic infectious disease caused by African swine fever virus (ASFV), which is listed as an animal epidemic disease that must be reported by The World Organization for Animal Health and that causes serious economic losses to China and even the whole world. Currently, the entry mechanism of ASFV is not fully understood. Especially in the early stages of virus entry, the host factors required for ASFV entry have not yet been identified and characterized. In this study, we demonstrated that ASFV externalized phosphatidylserine (PS) on the envelope functioned as viral apoptotic mimicry, which interacts with AXL, a tyrosine kinase receptor, to mediate ASFV entry into porcine alveolar macrophages (PAMs). We found that AXL was the most pronounced phosphatidylserine receptor (PSR) affecting ASFV entry in PAMs by RNA interference screening. Knockout AXL gene expression remarkably decreased ASFV internalization and replication in MA104 cells. Furthermore, the antibody against AXL extracellular domains effectively inhibited the ASFV entry. Consistent with these results, the deletion of the intracellular kinase domain of AXL and the treatment of the AXL inhibitor, R428, significantly inhibited the internalization of ASFV. Mechanistically, AXL facilitated the internalization of ASFV virions via macropinocytosis. Collectively, we provide evidence that AXL is a coreceptor for ASFV entry into PAMs, which expands our knowledge of ASFV entry and provides a theoretical basis for identifying new antiviral targets. IMPORTANCE African swine fever (ASF) is a highly contagious infectious disease caused by the ASF virus (ASFV), with a mortality rate of up to 100%. ASFV has caused huge economic losses to pig farming worldwide. Specific cellular surface receptors are considered crucial determinants of ASFV tropism. However, the host factors required for ASFV entry have not yet been identified, and the molecular mechanism of its entry remains unclear. Here, we found that ASFV utilized phosphatidylserine (PS) on the surface of virions to masquerade as apoptotic mimicry and facilitated virus entry by interacting with host factor AXL. We found that knockout of AXL remarkably decreased ASFV internalization and replication. The antibody against AXL extracellular domains and AXL inhibitor R428 significantly inhibited the internalization of ASFV via macropinocytosis. The current work deepens our understanding of ASFV entry and provides clues for the development of antiviral drugs to control ASFV infection.


Assuntos
Febre Suína Africana , Receptor Tirosina Quinase Axl , Interações entre Hospedeiro e Microrganismos , Internalização do Vírus , Animais , Febre Suína Africana/virologia , Vírus da Febre Suína Africana/genética , Suínos , Receptor Tirosina Quinase Axl/genética , Receptor Tirosina Quinase Axl/metabolismo , Macrófagos Alveolares/virologia , Técnicas de Inativação de Genes , Linhagem Celular , Envelope Viral/metabolismo , Ligação Viral , Domínios Proteicos
8.
Plant Physiol ; 192(3): 2015-2029, 2023 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-36721923

RESUMO

As the main fungal etiologic agent of apple (Malus domestica) replant disease (ARD), Fusarium solani seriously damages apple roots. Ethylene response factors (ERFs) play an important role in plant resistance to biotic stress. Here, we show that MdERF114 is expressed during F. solani infections and positively regulates the resistance of apple roots to F. solani. Yeast one-hybrid, dual-luciferase, electrophoretic mobility shift assays and determinations of lignin content indicated that MdERF114 directly binds the GCC-box of the MdPEROXIDASE63 (MdPRX63) promoter and activates its expression, resulting in lignin deposition in apple roots and increased resistance to F. solani. We identified a WRKY family transcription factor, MdWRKY75, that binds to the W-box of the MdERF114 promoter. Overexpression of MdWRKY75 enhanced resistance of apple roots to F. solani. MdMYB8 interacted with MdERF114 to enhance resistance to F. solani by promoting the binding of MdERF114 to the MdPRX63 promoter. In summary, our findings reveal that the MdWRKY75-MdERF114-MdMYB8-MdPRX63 module is required for apple resistance to F. solani and the application of this mechanism by Agrobacterium rhizogenes-mediated root transformation provides a promising strategy to prevent ARD.


Assuntos
Fusarium , Malus , Malus/metabolismo , Lignina/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
9.
Chemistry ; 30(3): e202302997, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-37823329

RESUMO

The oxygen reduction reaction (ORR) is the key reaction in metal air and fuel cells. Among the catalysts that promote ORR, carbon-based metal-free catalysts are getting more attention because of their maximum atom utilization, effective active sites and satisfactory catalytic activity and stability. However, the pyrolysis synthesis of these carbons resulted in disordered porosities and uncontrolled catalytic sites, which hindered us in realizing the catalysts' design, the optimization of catalyst performance and the elucidation of structure-property relationship at the molecular level. Covalent organic frameworks (COFs) constructed with designable building blocks have been employed as metal-free electrocatalysts for the ORR due to their controlled skeletons, tailored pores size and environments, as well as well-defined location and kinds of catalytic sites. In this Concept article, the development of metal-free COFs for the ORR is summarized, and different strategies including skeletons regulation, linkages engineering and edge-sites modulation to improve the catalytic selectivity and activity are discussed. Furthermore, this Concept provides prospectives for designing and constructing powerful electrocatalysts based on the catalytic COFs.

10.
Neurochem Res ; 49(5): 1212-1225, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38381247

RESUMO

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons. LncRNA small nucleolar RNA host gene 14 (SNHG14) was found to promote neuron injury in PD. Here, we investigated the mechanisms of SNHG14 in PD process. In vivo or in vitro PD model was established by using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice or 1-methyl-4-phenylpyridinium (MPP +)-stimulated SK-N-SH cells. The expression of genes and proteins was measured by qRT-PCR and Western blot. In vitro assays were conducted using ELISA, CCK-8, colony formation, EdU, flow cytometry, and Western blot assays, respectively. The oxidative stress was evaluated by determining the production of superoxide dismutase (SOD) and malondialdehyde (MDA). The direct interactions between miR-375-3p and NFAT5 (Nuclear factor of activated T-cells 5) or SNHG14 was verified using dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. SNHG14 and NFAT5 were elevated, while miR-375-3p was decreased in MPTP-mediated PD mouse model and MPP + -induced SK-N-SH cells. Knockdown of SNHG14 or NFAT5, or overexpression of miR-375-3p reversed MPP + -induced neuronal apoptosis, inflammation, and oxidative stress. Mechanistically, SNHG14 directly bound to miR-375, which targeted NFAT5. Inhibition of miR-375-3p abolished the inhibitory activity of SNHG14 knockdown on MPP + -evoked neuronal damage. Besides that, NFAT5 up-regulation counteracted the effects of miR-375-3p on MPP + -mediated neuronal damage. SNHG14 contributed to MPP + -induced neuronal injury by miR-375/NFAT5 axis, suggesting a new insight into the pathogenesis of PD.


Assuntos
Neurônios Dopaminérgicos , MicroRNAs , Doença de Parkinson , RNA Longo não Codificante , Animais , Camundongos , 1-Metil-4-fenilpiridínio , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Neurônios Dopaminérgicos/metabolismo , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Estresse Oxidativo , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
11.
BMC Infect Dis ; 24(1): 675, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38971721

RESUMO

Pleural empyema can lead to significant morbidity and mortality despite chest drainage and antibiotic treatment, necessitating novel and minimally invasive interventions. Fusobacterium nucleatum is an obligate anaerobe found in the human oral and gut microbiota. Advances in sequencing and puncture techniques have made it common to detect anaerobic bacteria in empyema cases. In this report, we describe the case of a 65-year-old man with hypertension who presented with a left-sided encapsulated pleural effusion. Initial fluid analysis using metagenomic next-generation sequencing (mNGS) revealed the presence of Fusobacterium nucleatum and Aspergillus chevalieri. Unfortunately, the patient experienced worsening pleural effusion despite drainage and antimicrobial therapy. Ultimately, successful treatment was achieved through intrapleural metronidazole therapy in conjunction with systemic antibiotics. The present case showed that intrapleural antibiotic therapy is a promising measure for pleural empyema.


Assuntos
Antibacterianos , Empiema Pleural , Fusobacterium nucleatum , Terapia de Salvação , Humanos , Masculino , Idoso , Empiema Pleural/tratamento farmacológico , Empiema Pleural/microbiologia , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Fusobacterium nucleatum/efeitos dos fármacos , Fusobacterium nucleatum/isolamento & purificação , Fusobacterium nucleatum/genética , Infecções por Fusobacterium/tratamento farmacológico , Infecções por Fusobacterium/complicações , Infecções por Fusobacterium/microbiologia , Metronidazol/uso terapêutico , Metronidazol/administração & dosagem , Sequenciamento de Nucleotídeos em Larga Escala , Resultado do Tratamento
12.
J Mater Sci Mater Med ; 35(1): 35, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38900360

RESUMO

Bioabsorbable sutures can improve the medical functions of existing non-absorbable sutures, and may produce new medical effects, and are expected to become a new generation of medical degradable materials. In this study, the cytocompatibility of triclosan coated polyglactin910 sutures (CTS-PLGA910) was analyzed and different concentrations of sutures were prepared. The effects of sutures on the cytotoxicity and cell proliferation of HUVEC were studied by CCK-8 assay. The hemolysis, total antioxidant capacity (T-AOC) activity and nitric oxide (NO) content were investigated to improve the blood compatibility of sutures. The results showed that the hemolysis rate of CTS-PLGA910 was less than 5%. After treatment on HUVEC cells for 48 and 72 h, there was no significant change in NO content in CTS-PLGA910 groups compared with the control group, while T-AOC activity and antioxidant capacity were significantly increased in medium and high dose groups. In summary, the blood compatibility and cell compatibility were significantly improved, which provided a basis for the clinical application of sutures in the future.


Assuntos
Proliferação de Células , Materiais Revestidos Biocompatíveis , Células Endoteliais da Veia Umbilical Humana , Teste de Materiais , Poliglactina 910 , Suturas , Triclosan , Humanos , Triclosan/farmacologia , Triclosan/química , Poliglactina 910/química , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Proliferação de Células/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/química , Materiais Biocompatíveis/química , Óxido Nítrico/metabolismo , Sobrevivência Celular/efeitos dos fármacos
13.
Angew Chem Int Ed Engl ; 63(5): e202317785, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38085127

RESUMO

Covalent organic frameworks (COFs) have been utilized for catalyzing the reduction of carbon dioxide (CO2RR) due to their atomic metal centers and controllable pore channels, which are facilitated by different covalent bonds. However, the exploration of boron-based linkages in these catalytic COFs has been limited owing to potential instability. Herein, we present the construction of boronic ester-linked COFs through nucleophilic substitution reactions in order to catalyze the CO2 RR. The inclusion of abundant fluorine atoms within the frameworks enhances their hydrophobicity and subsequently improves water tolerance and chemical stability of COFs. The content of boron atoms in the COF linkages was carefully controlled, with COFs featuring a higher density of boron atoms exhibiting increased electronic conductivity, enhanced reductive ability, and stronger binding affinity towards CO2 . Consequently, these COFs demonstrate improved activity and selectivity. The optimized COFs achieve the highest activity, achieving a turnover frequency of 1695.3 h-1 and a CO selectivity of 95.0 % at -0.9 V. Operando synchrotron radiation measurements confirm the stability of Co (II) atoms as catalytically active sites. By successfully constructing boronic ester-linked COFs, we not only address potential instability concerns but also achieve exceptional catalytic performance for CO2 RR.

14.
Angew Chem Int Ed Engl ; 63(16): e202319247, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38381931

RESUMO

Binding water molecules to polar sites in covalent organic frameworks (COFs) is inevitable, but the corresponding solvent effects in electrocatalytic process have been largely overlooked. Herein, we investigate the solvent effects on COFs for catalyzing the oxygen reduction reaction (ORR). Our designed COFs incorporated different kinds of nitrogen atoms (imine N, pyridine N, and phenazine N), enabling tunable interactions with water molecules. These interactions play a crucial role in modulating electronic states and altering the catalytic centers within the COFs. Among the synthesized COFs, the one with pyridine N atoms exhibits the highest activity, with characterized by a half-wave potential of 0.78 V and a mass activity of 0.32 A mg-1, which surpass those from other metal-free COFs. Theoretical calculations further reveal that the enhanced activity can be attributed to the stronger binding ability of *OOH intermediates to the carbon atoms adjacent to the pyridine N sites. This work sheds light on the significance of considering solvent effects on COFs in electrocatalytic systems, providing valuable insights into their design and optimization for improved performance.

15.
Angew Chem Int Ed Engl ; 63(20): e202401750, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38407379

RESUMO

The catalytic performance for electrocatalytic CO2 reduction reaction (CO2RR) depends on the binding strength of the reactants and intermediates. Covalent organic frameworks (COFs) have been adopted to catalyze CO2RR, and their binding abilities are tuned via constructing donor-acceptor (DA) systems. However, most DA COFs have single donor and acceptor units, which caused wide-range but lacking accuracy in modulating the binding strength of intermediates. More elaborate regulation of the interactions with intermediates are necessary and challenge to construct high-efficiency catalysts. Herein, the three-component COF with D-A-A units was first constructed by introducing electron-rich diarylamine unit, electron-deficient benzothiazole and Co-porphyrin units. Compared with two-component COFs, the designed COF exhibit elevated electronic conductivity, enhanced reducibility, high efficiency charge transfer, further improving the electrocatalytic CO2RR performance with the faradic efficiency of 97.2 % at -0.8 V and high activity with the partial current density of 27.85 mA cm-2 at -1.0 V which exceed other two-component COFs. Theoretical calculations demonstrate that catalytic sites in three-component COF have suitable binding ability of the intermediates, which are benefit for formation of *COOH and desorption of *CO. This work offers valuable insights for the advancement of multi-component COFs, enabling modulated charge transfer to improve the CO2RR activity.

16.
J Cardiovasc Electrophysiol ; 34(5): 1302-1304, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37003264

RESUMO

INTRODUCTION: We describe one rare case of successful ablation of a right epicardial accessory pathway (AP) via the right ventricular diverticulum in a patient with Wolff-Parkinson-White syndrome. METHODS: A 42-year-old woman was referred to the hospital for a catheter ablation of Wolf-Parkinson-White syndrome. The earliest activation was shown to be present in the region of the tricuspid annulus. However, ablation had no effect on the AP. RESULTS: We decided to do a selected angiography, in which a big diverticulum near the right tricuspid annulus was shown to be present. Ablation in this region successfully repressed the AP without any recurrences within a follow-up period of 12 months. CONCLUSION: The ventricular diverticulum-mediated AP is a novel variant of pre-excitation. It can serve as an anatomical substrate of supraventricular tachycardia, and can be ablated endocardially using an irrigation tip catheter within the diverticulum.


Assuntos
Feixe Acessório Atrioventricular , Ablação por Cateter , Divertículo , Cardiopatias Congênitas , Síndrome de Wolff-Parkinson-White , Humanos , Síndrome de Wolff-Parkinson-White/complicações , Síndrome de Wolff-Parkinson-White/diagnóstico por imagem , Síndrome de Wolff-Parkinson-White/cirurgia , Feixe Acessório Atrioventricular/diagnóstico por imagem , Feixe Acessório Atrioventricular/cirurgia , Cardiopatias Congênitas/cirurgia , Fascículo Atrioventricular , Divertículo/complicações , Divertículo/diagnóstico por imagem , Divertículo/cirurgia , Eletrocardiografia
17.
Inflamm Res ; 72(3): 429-442, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36583755

RESUMO

OBJECTIVE: Accumulating evidence has demonstrated that N6-methyladenosine (m6A) plays important roles in many major diseases, including atherosclerosis (AS). In the present study, we aimed to explore the transcriptomic m6A landscape of endothelial function-associated genes and identify potential regulators in AS progression. METHODS: The GEO data (GSE142386) from MeRIP-seq in human umbilical vein endothelial cells (HUVECs) with METTL3 knocked down or not were analyzed. RNA-seq was performed to identify differences in gene expression. Gene ontology (GO) functional and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were conducted to evaluate the potential functions of the differentially expressed genes. MeRIP-qPCR was used to measure the m6A and mRNA levels of the top 8 downregulated genes, and NPC1L1 was selected as the candidate gene. Oxidized low-density lipoprotein (ox-LDL) was used to stimulate HUVECs, and METTL3 or NPC1L1 was silenced in ox-LDL-treated cells. And Transwell, ELISA, and cell apoptosis assays were performed to assess cell functional injury. ApoE-/- mice were fed with high-fat diet for 8 weeks to establish an AS model, and adenovirus-mediated NPC1L1 shRNA or NC shRNA was injected into the mice through the tail vein. Mouse aortic tissue damage and plaque deposition were evaluated by H&E, Oil Red O, and TUNEL staining. RESULTS: One hundred and ninety-four hypermethylated m6A peaks and 222 hypomethylated peaks were detected in response to knockdown of METTL3. Genes with altered m6A peaks were significantly involved in the histone modification, enzyme activity, and formation of multiple complexes and were predominantly enriched in the MAPK pathway. NPC1L1 was a most significantly downregulated transcript in response to knockdown of METTL3. Moreover, knockdown of NPC1L1 or de-m6A (METTL3 knockdown)-mediated downregulation of NPC1L1 could improve ox-LDL-induced dysfunction of HUVECs in vitro and high-fat diet-induced atherosclerotic plaque in vivo, which was associated with the inactivation of the MAPK pathway. CONCLUSION: METTL3-mediated NPC1L1 mRNA hypermethylation facilitates AS progression by regulating the MAPK pathway, and NPC1L1 may be a novel target for the treatment of AS.


Assuntos
Aterosclerose , Proteínas de Membrana Transportadoras , Metiltransferases , Animais , Humanos , Masculino , Camundongos , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Células Endoteliais da Veia Umbilical Humana , Metilação , Metiltransferases/metabolismo , Proteínas de Membrana Transportadoras/genética , RNA Mensageiro/metabolismo
18.
Environ Sci Technol ; 57(38): 14384-14395, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37694860

RESUMO

Ferrihydrite is one of the most reactive iron (Fe) (oxyhydr)oxides in soils, but the adsorption mechanisms of glyphosate, the most widely used herbicide, on ferrihydrite remain unknown. Here, we determined the adsorption mechanisms of glyphosate on pristine and Al-substituted ferrihydrites with aggregated and dispersed states using macroscopic adsorption experiments, zeta potential, phosphorus K-edge X-ray absorption near-edge structure spectroscopy, in situ attenuated total reflectance Fourier transform infrared spectroscopy coupled with two-dimensional correlation spectroscopy, and multivariate curve resolution analyses. Aggregation of ferrihydrite decreases the glyphosate adsorption capacity. The partial substitution of Al in ferrihydrite inhibits glyphosate adsorption on aggregated ferrihydrite due to the decrease of external specific surface area, while it promotes glyphosate adsorption on dispersed ferrihydrite, which is ascribed to the increase of surface positive charge. Glyphosate predominately forms protonated and deprotonated, depending on the sorption pH, monodentate-mononuclear complexes (MMH1/MMH0, 77-90%) on ferrihydrites, besides minor deprotonated bidentate-binuclear complexes (BBH0, 23-10%). Both Al incorporation and a low pH favor the formation of the BB complex. The adsorbed glyphosate preferentially forms the MM complex on ferrihydrite and preferentially bonds with the Al-OH sites on Al-substituted ferrihydrite. These new insights are expected to be useful in predicting the environmental fate of glyphosate in ferrihydrite-rich environments.


Assuntos
Herbicidas , Ferro , Adsorção , Glifosato
19.
Ecotoxicol Environ Saf ; 262: 115150, 2023 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-37336090

RESUMO

Carbapenem-resistant Enterobacteriaceae (CRE) poses major health risks worldwide. Most studies have focused on carbapenem resistance in Klebsiella pneumoniae and Escherichia coli; however, the occurrence and transmission of carbapenem-resistant Citrobacter spp. (CRCS) are poorly understood. In this study, we investigated the occurrence and potential transmission patterns of CRCS in different functional areas of an urban wastewater treatment plant (WWTP) and connecting rivers during one-year monitoring in Shandong Province, China. In total, 14 CRCS were detected in 376 environmental samples, including those from the WWTP inlet (n = 7), WWTP anaerobic tank (n = 2), and rivers (n = 5). Citrobacter braakii (n = 6) was the dominant subtype among 14 CRCS isolates, followed by Citrobacter freundii (n = 5), Citrobacter sedlakii (n = 2), and Citrobacter werkmanii (n = 1). All CRCS were resistant to imipenem, meropenem, ampicillin, amoxicillin/clavulanic acid, cefotaxime, ceftazidime, trimethoprim/sulfamethoxazole, and ciprofloxacin. Plasmid analysis showed that the blaKPC-2 gene was located on IncN and IncFII (Yp) plasmids, whereas the blaNDM gene was located on IncX3 and IncN2 plasmids. Clonal transmission of CRCS harboring carbapenem genes occurred between the WWTP and connecting rivers on a temporal or spatial scale. High genomic relatedness of NDM-5-producing C. sedlakii was identified between river water and WWTP aerosol, suggesting a potential exposure risk of CRCS for workers and surrounding residents near the WWTP. Furthermore, NDM-5-producing C. sedlakii isolated from rivers was related to C. sedlakii isolated from soil and well water in different regions of China, indicating that NDM-5-producing C. sedlakii may be widespread in China. These findings indicate that rare healthcare-associated pathogens such as CRCS can contribute to widespread carbapenem production in the environment; thus, CRCS should be continuously monitored.

20.
BMC Med Inform Decis Mak ; 23(1): 165, 2023 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-37620904

RESUMO

AIMS: Heart failure (HF) is one of the common adverse cardiovascular events after acute myocardial infarction (AMI), but the predictive efficacy of numerous machine learning (ML) built models is unclear. This study aimed to build an optimal model to predict the occurrence of HF in AMI patients by comparing seven ML algorithms. METHODS: Cohort 1 included AMI patients from 2018 to 2019 divided into HF and control groups. All first routine test data of the study subjects were collected as the features to be selected for the model, and seven ML algorithms with screenable features were evaluated. Cohort 2 contains AMI patients from 2020 to 2021 to establish an early warning model with external validation. ROC curve and DCA curve to analyze the diagnostic efficacy and clinical benefit of the model respectively. RESULTS: The best performer among the seven ML algorithms was XgBoost, and the features of XgBoost algorithm for troponin I, triglycerides, urine red blood cell count, γ-glutamyl transpeptidase, glucose, urine specific gravity, prothrombin time, prealbumin, and urea were ranked high in importance. The AUC of the HF-Lab9 prediction model built by the XgBoost algorithm was 0.966 and had good clinical benefits. CONCLUSIONS: This study screened the optimal ML algorithm as XgBoost and developed the model HF-Lab9 will improve the accuracy of clinicians in assessing the occurrence of HF after AMI and provide a reference for the selection of subsequent model-building algorithms.


Assuntos
Insuficiência Cardíaca , Infarto do Miocárdio , Humanos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico , Algoritmos , Aprendizado de Máquina , Curva ROC
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