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1.
Nature ; 626(7997): 86-91, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38297172

RESUMEN

Electrolysis that reduces carbon dioxide (CO2) to useful chemicals can, in principle, contribute to a more sustainable and carbon-neutral future1-6. However, it remains challenging to develop this into a robust process because efficient conversion typically requires alkaline conditions in which CO2 precipitates as carbonate, and this limits carbon utilization and the stability of the system7-12. Strategies such as physical washing, pulsed operation and the use of dipolar membranes can partially alleviate these problems but do not fully resolve them11,13-15. CO2 electrolysis in acid electrolyte, where carbonate does not form, has therefore been explored as an ultimately more workable solution16-18. Herein we develop a proton-exchange membrane system that reduces CO2 to formic acid at a catalyst that is derived from waste lead-acid batteries and in which a lattice carbon activation mechanism contributes. When coupling CO2 reduction with hydrogen oxidation, formic acid is produced with over 93% Faradaic efficiency. The system is compatible with start-up/shut-down processes, achieves nearly 91% single-pass conversion efficiency for CO2 at a current density of 600 mA cm-2 and cell voltage of 2.2 V and is shown to operate continuously for more than 5,200 h. We expect that this exceptional performance, enabled by the use of a robust and efficient catalyst, stable three-phase interface and durable membrane, will help advance the development of carbon-neutral technologies.

2.
Nucleic Acids Res ; 52(8): 4556-4574, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38554114

RESUMEN

Transcriptional pausing aids gene regulation by cellular RNA polymerases (RNAPs). A surface-exposed domain inserted into the catalytic trigger loop (TL) of Escherichia coli RNAP, called SI3, modulates pausing and is essential for growth. Here we describe a viable E. coli strain lacking SI3 enabled by a suppressor TL substitution (ß'Ala941→Thr; ΔSI3*). ΔSI3* increased transcription rate in vitro relative to ΔSI3, possibly explaining its viability, but retained both positive and negative effects of ΔSI3 on pausing. ΔSI3* inhibited pauses stabilized by nascent RNA structures (pause hairpins; PHs) but enhanced other pauses. Using NET-seq, we found that ΔSI3*-enhanced pauses resemble the consensus elemental pause sequence whereas sequences at ΔSI3*-suppressed pauses, which exhibited greater association with PHs, were more divergent. ΔSI3*-suppressed pauses also were associated with apparent pausing one nucleotide upstream from the consensus sequence, often generating tandem pause sites. These '-2 pauses' were stimulated by pyrophosphate in vitro and by addition of apyrase to degrade residual NTPs during NET-seq sample processing. We propose that some pauses are readily reversible by pyrophosphorolysis or single-nucleotide cleavage. Our results document multiple ways that SI3 modulates pausing in vivo and may explain discrepancies in consensus pause sequences in some NET-seq studies.


Asunto(s)
ARN Polimerasas Dirigidas por ADN , Proteínas de Escherichia coli , Escherichia coli , Transcripción Genética , ARN Polimerasas Dirigidas por ADN/química , ARN Polimerasas Dirigidas por ADN/genética , ARN Polimerasas Dirigidas por ADN/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Regulación Bacteriana de la Expresión Génica , Dominios Proteicos
3.
Plant Physiol ; 195(4): 2787-2798, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-38652695

RESUMEN

Centromeres in most multicellular eukaryotes are composed of long arrays of repetitive DNA sequences. Interestingly, several transposable elements, including the well-known long terminal repeat centromeric retrotransposon of maize (CRM), were found to be enriched in functional centromeres marked by the centromeric histone H3 (CENH3). Here, we report a centromeric long interspersed nuclear element (LINE), Celine, in Populus species. Celine has colonized preferentially in the CENH3-associated chromatin of every poplar chromosome, with 84% of the Celine elements localized in the CENH3-binding domains. In contrast, only 51% of the CRM elements were bound to CENH3 domains in Populus trichocarpa. These results suggest different centromere targeting mechanisms employed by Celine and CRM elements. Nevertheless, the high target specificity seems to be detrimental to further amplification of the Celine elements, leading to a shorter life span and patchy distribution among plant species compared with the CRM elements. Using a phylogenetically guided approach, we were able to identify Celine-like LINE elements in tea plant (Camellia sinensis) and green ash tree (Fraxinus pennsylvanica). The centromeric localization of these Celine-like LINEs was confirmed in both species. We demonstrate that the centromere targeting property of Celine-like LINEs is of primitive origin and has been conserved among distantly related plant species.


Asunto(s)
Centrómero , Cromosomas de las Plantas , Populus , Retroelementos , Populus/genética , Centrómero/genética , Centrómero/metabolismo , Cromosomas de las Plantas/genética , Retroelementos/genética , Elementos de Nucleótido Esparcido Largo/genética , Filogenia , Histonas/metabolismo , Histonas/genética
4.
Plant Physiol ; 195(1): 652-670, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38412470

RESUMEN

Poplar (Populus) is a well-established model system for tree genomics and molecular breeding, and hybrid poplar is widely used in forest plantations. However, distinguishing its diploid homologous chromosomes is difficult, complicating advanced functional studies on specific alleles. In this study, we applied a trio-binning design and PacBio high-fidelity long-read sequencing to obtain haplotype-phased telomere-to-telomere genome assemblies for the 2 parents of the well-studied F1 hybrid "84K" (Populus alba × Populus tremula var. glandulosa). Almost all chromosomes, including the telomeres and centromeres, were completely assembled for each haplotype subgenome apart from 2 small gaps on one chromosome. By incorporating information from these haplotype assemblies and extensive RNA-seq data, we analyzed gene expression patterns between the 2 subgenomes and alleles. Transcription bias at the subgenome level was not uncovered, but extensive-expression differences were detected between alleles. We developed machine-learning (ML) models to predict allele-specific expression (ASE) with high accuracy and identified underlying genome features most highly influencing ASE. One of our models with 15 predictor variables achieved 77% accuracy on the training set and 74% accuracy on the testing set. ML models identified gene body CHG methylation, sequence divergence, and transposon occupancy both upstream and downstream of alleles as important factors for ASE. Our haplotype-phased genome assemblies and ML strategy highlight an avenue for functional studies in Populus and provide additional tools for studying ASE and heterosis in hybrids.


Asunto(s)
Alelos , Genoma de Planta , Populus , Populus/genética , Genoma de Planta/genética , Regulación de la Expresión Génica de las Plantas , Haplotipos/genética , Hibridación Genética , Aprendizaje Automático
6.
Nano Lett ; 24(13): 3961-3970, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38526195

RESUMEN

Developing a high-performance membrane electrode assembly (MEA) poses a formidable challenge for fuel cells, which lies in achieving both high metal loading and efficient catalytic activity concurrently for MEA catalysts. Here, we introduce a porous Co@NC carrier to synthesize sub-4 nm PtCo intermetallic nanocrystals, achieving an impressive Pt loading of 27 wt %. The PtCo-CoNC catalyst demonstrates exceptional catalytic activity and remarkable stability for the oxygen reduction reaction. Advanced characterization techniques and theoretical calculations emphasize the synergistic effect between PtCo alloys and single Co atoms, which enhances the desorption of the OH* intermediate. Furthermore, the PtCo-CoNC-based cathode delivers a high power density of 1.22 W cm-2 in the MEA test owing to the enhanced mass transport, which is verified by the simulation results of the O2 distributions and current density inside the catalyst layer. This study lays the groundwork for the design of efficient catalysts with practical applications in fuel cells.

7.
J Am Chem Soc ; 146(22): 15356-15365, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38773696

RESUMEN

Electrosynthesis has emerged as an enticing solution for hydrogen peroxide (H2O2) production. However, efficient H2O2 generation encounters challenges related to the robust gas-liquid-solid interface within electrochemical reactors. In this work, we introduce an effective hydrophobic coating modified by iron (Fe) sites to optimize the reaction microenvironment. This modification aims to mitigate radical corrosion through Fe(II)/Fe(III) redox chemistry, reinforcing the reaction microenvironment at the three-phase interface. Consequently, we achieved a remarkable yield of up to 336.1 mmol h-1 with sustained catalyst operation for an extensive duration of 230 h at 200 mA cm-2 without causing damage to the reaction interface. Additionally, the Faradaic efficiency of H2O2 exceeded 90% across a broad range of test current densities. This surface redox chemistry approach for manipulating the reaction microenvironment not only advances long-term H2O2 electrosynthesis but also holds promise for other gas-starvation electrochemical reactions.

8.
J Am Chem Soc ; 146(29): 20530-20538, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-38991189

RESUMEN

The electrochemical reduction reaction of carbon dioxide (CO2RR) into valuable products offers notable economic benefits and contributes to environmental sustainability. However, precisely controlling the reaction pathways and selectively converting key intermediates pose considerable challenges. In this study, our theoretical calculations reveal that the active sites with different states of copper atoms (1-3-5-7-9) play a pivotal role in the adsorption behavior of the *CHO critical intermediate. This behavior dictates the subsequent hydrogenation and coupling steps, ultimately influencing the formation of the desired products. Consequently, we designed two model electrocatalysts comprising Cu single atoms and particles supported on CeO2. This design enables controlled *CHO intermediate transformation through either hydrogenation with *H or coupling with *CO, leading to a highly selective CO2RR. Notably, our selective control strategy tunes the Faradaic efficiency from 61.1% for ethylene (C2H4) to 61.2% for methane (CH4). Additionally, the catalyst demonstrated a high current density and remarkable stability, exceeding 500 h of operation. This work not only provides efficient catalysts for selective CO2RR but also offers valuable insights into tailoring surface chemistry and designing catalysts for precise control over catalytic processes to achieve targeted product generation in CO2RR technology.

9.
J Am Chem Soc ; 2024 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-38176108

RESUMEN

Seawater-flow- and -evaporation-induced electricity generation holds significant promise in advancing next-generation sustainable energy technologies. This method relies on the electrokinetic effect but faces substantial limitations when operating in a highly ion-concentrated environment, for example, natural seawater. We present herein a novel solution using calcium-based metal-organic frameworks (MOFs, C12H6Ca2O19·2H2O) for seawater-evaporation-induced electricity generation. Remarkably, Ca-MOFs show an open-circuit voltage of 0.4 V and a short-circuit current of 14 µA when immersed in seawater under natural conditions. Our experiments and simulations revealed that sodium (Na) ions selectively transport within sub-nanochannels of these synthetic superhydrophilic MOFs. This selective ion transport engenders a unipolar solution flow, which drives the electricity generation behavior in seawater. This work not only showcases an effective Ca-MOF for electricity generation through seawater flow/evaporation but also contributes significantly to our understanding of water-driven energy harvesting technologies and their potential applications beyond this specific context.

10.
J Am Chem Soc ; 146(32): 22650-22660, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39080509

RESUMEN

Iron-nitrogen-carbon (Fe-N-C) catalysts, although the most active platinum-free option for the cathodic oxygen reduction reaction (ORR), suffer from poor durability due to the Fe leaching and consequent Fenton effect, limiting their practical application in low-temperature fuel cells. This work demonstrates an integrated catalyst of a platinum-iron (PtFe) alloy planted in an Fe-N-C matrix (PtFe/Fe-N-C) to address this challenge. This novel catalyst exhibits both high-efficiency activity and stability, as evidenced by its impressive half-wave potential (E1/2) of 0.93 V versus reversible hydrogen electrode (vs RHE) and minimal 7 mV decay even after 50,000 potential cycles. Remarkably, it exhibits a very low hydrogen peroxide (H2O2) yield (0.07%) at 0.6 V and maintains this performance with negligible change after 10,000 potential cycles. Fuel cells assembled with this cathode PtFe/Fe-N-C catalyst show exceptional durability, with only 8 mV voltage loss at 0.8 A cm-2 after 30,000 cycles and ignorable current degradation at a voltage of 0.6 V over 85 h. Comprehensive in situ experiments and theoretical calculations reveal that oxygen species spillover from Fe-N-C to PtFe alloy not only inhibits H2O2 production but also eliminates harmful oxygenated radicals. This work paves the way for the design of highly efficient and stable ORR catalysts and has significant implications for the development of next-generation fuel cells.

11.
Anal Chem ; 96(26): 10835-10840, 2024 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-38889097

RESUMEN

G-quadruplex (G4) DNA is considered as a prospective therapeutic target due to its potential biological significance. To understand G4 biological roles and function, a G4-specific fluorescent probe is necessary. However, it is difficult for versatile G4 to precisely recognize without perturbing their folding dynamics. Herein, we reported that flavone P0 can be a fluorescent probe for G4 DNA-specific recognition and have developed a highly selective detection of K+ ion by dimeric G4/P0 system. When comparing various nucleic acid structures, including G4, i-motif, ss/ds-DNA, and triplex, an apparent fluorescence enhancement is observed in the presence of G4 DNA for 85-fold, but only 8-fold for non-G4 DNA. Furthermore, based on fluorescent probe of flavone P0 for G4 DNA screening, the noncovalent dimeric G4/P0 system is exploited as a K+ sensor, that selectively responds to K+ with a 513-fold fluorescence enhancement and a detection range for K+ ion concentration from 0 to 500 mM. This K+ sensor also has a remarkably anti-interference ability for other metal cations, especially for a high concentration of Na+. These results have demonstrated that flavone P0 is an efficient tool for monitoring G-quadruplex DNA and endows flavone P0 with bioanalytical and medicinal applications.


Asunto(s)
ADN , Flavonas , Colorantes Fluorescentes , G-Cuádruplex , Potasio , Flavonas/química , Colorantes Fluorescentes/química , Potasio/química , Potasio/análisis , ADN/química , Espectrometría de Fluorescencia
12.
Anal Chem ; 96(9): 3914-3924, 2024 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-38387027

RESUMEN

Wearable, noninvasive sensors enable the continuous monitoring of metabolites in sweat and provide clinical information related to an individual's health and disease states. Uric acid (UA) is a key indicator highly associated with gout, hyperuricaemia, hypertension, kidney disease, and Lesch-Nyhan syndrome. However, the detection of UA levels typically relies on invasive blood tests. Therefore, developing a wearable device for noninvasive monitoring of UA concentrations in sweat could facilitate real-time personalized disease prevention. Here, we introduce 1,3,6,8-pyrene tetrasulfonic acid sodium salt (PyTS) as a bifunctional molecule functionalized with Ti3C2Tx via π-π conjugation to design nonenzymatic wearable sensors for sensitive and selective detection of UA concentration in human sweat. PyTS@Ti3C2Tx provides many oxidation-reduction active groups to enhance the electrocatalytic ability of the UA oxidation reaction. The PyTS@Ti3C2Tx-based electrochemical sensor demonstrates highly sensitive detection of UA in the concentration range of 5 µM-100 µM, exhibiting a lower detection limit of 0.48 µM compared to the uricase-based sensor (0.84 µM). In volunteers, the PyTS@Ti3C2Tx-based wearable sensor is integrated with flexible microfluidic sweat sampling and wireless electronics to enable real-time monitoring of UA levels during aerobic exercise. Simultaneously, it allows for comparison of blood UA levels via a commercial UA analyzer. Herein, this study provides a promising electrocatalyst strategy for nonenzymatic electrochemical UA sensor, enabling noninvasive real-time monitoring of UA levels in human sweat and personalized disease prevention.


Asunto(s)
Técnicas Biosensibles , Nitritos , Elementos de Transición , Dispositivos Electrónicos Vestibles , Humanos , Ácido Úrico/análisis , Titanio/análisis , Sudor/química
13.
Anal Chem ; 96(21): 8594-8603, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38718350

RESUMEN

Solid-contact ion-selective electrodes (SC-ISEs) with ionophore-based polymer-sensitive membranes have been the major devices in wearable sweat sensors toward electrolyte analysis. However, the toxicity of ionophores in ion-selective membranes (ISMs), for example, valinomycin (K+ ion carrier), is a significant challenge, since the ISM directly contacts the skin during the tests. Herein, we report coating a hydrogel of graphene oxide-poly(vinyl alcohol) (GO-PVA) on the ISM to fabricate hydrogel-based SC-ISEs. The hydrogen bond interaction between GO sheets and PVA chains could enhance the mechanical strength through the formation of a cross-linking network. Comprehensive electrochemical tests have demonstrated that hydrogel-coated K+-SC-ISE maintains Nernstian response sensitivity, high selectivity, and anti-interference ability compared with uncoated K+-SC-ISE. A flexible hydrogel-based K+ sensing device was further fabricated with the integration of a solid-contact reference electrode, which has realized the monitoring of sweat K+ in real time. This work highlights the possibility of hydrogel coating for fabricating biocompatible wearable potentiometric sweat electrolyte sensors.

14.
New Phytol ; 242(5): 2043-2058, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38515251

RESUMEN

MicroRNAs are essential in plant development and stress resistance, but their specific roles in drought stress require further investigation. Here, we have uncovered that a Populus-specific microRNAs (miRNA), miR6445, targeting NAC (NAM, ATAF, and CUC) family genes, is involved in regulating drought tolerance of poplar. The expression level of miR6445 was significantly upregulated under drought stress; concomitantly, seven targeted NAC genes showed significant downregulation. Silencing the expression of miR6445 by short tandem target mimic technology significantly decreased the drought tolerance in poplar. Furthermore, 5' RACE experiments confirmed that miR6445 directly targeted NAC029. The overexpression lines of PtrNAC029 (OE-NAC029) showed increased sensitivity to drought compared with knockout lines (Crispr-NAC029), consistent with the drought-sensitive phenotype observed in miR6445-silenced strains. PtrNAC029 was further verified to directly bind to the promoters of glutathione S-transferase U23 (GSTU23) and inhibit its expression. Both Crispr-NAC029 and PtrGSTU23 overexpressing plants showed higher levels of PtrGSTU23 transcript and GST activity while accumulating less reactive oxygen species (ROS). Moreover, poplars overexpressing GSTU23 demonstrated enhanced drought tolerance. Taken together, our research reveals the crucial role of the miR6445-NAC029-GSTU23 module in enhancing poplar drought tolerance by regulating ROS homeostasis. This finding provides new molecular targets for improving the drought resistance of trees.


Asunto(s)
Resistencia a la Sequía , Glutatión Transferasa , MicroARNs , Proteínas de Plantas , Populus , Especies Reactivas de Oxígeno , Adaptación Fisiológica , Secuencia de Bases , Depuradores de Radicales Libres/metabolismo , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Glutatión Transferasa/genética , Glutatión Transferasa/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente , Populus/genética , Populus/fisiología , Populus/enzimología , Regiones Promotoras Genéticas/genética , Especies Reactivas de Oxígeno/metabolismo , Estrés Fisiológico/genética
15.
Opt Lett ; 49(15): 4210-4213, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39090896

RESUMEN

The large-scale deployment of quantum secret sharing (QSS) in quantum networks is currently challenging due to the requirements for the generation and distribution of multipartite entanglement states. Here we present an efficient source-independent QSS protocol utilizing entangled photon pairs in quantum networks. Through the post-matching method, which means the measurement events in the same basis are matched, the key rate is almost independent of the number of participants. In addition, the unconditional security of our QSS against internal and external eavesdroppers can be proved by introducing an equivalent virtual protocol. Our protocol has great performance and technical advantages in future quantum networks.

16.
J Org Chem ; 89(7): 4877-4887, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38457276

RESUMEN

General and convenient visible-light-promoted alkylsulfonylation and cyanoalkylsulfonylation of MBH adducts have been developed through the multicomponent insertion of sulfur dioxide, enabling the assembly of two C-S bonds to generate structurally diverse allylic alkylsulfones (43 examples in total). The reaction of MBH adducts with potassium alkyltrifluoroborates and 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct afforded sulfones with generally good yields. Notably, the addition of N,N,N',N'-tetramethylethylenediamine as a base into the photocatalytic system led to yielding an alkyl sulfonyl unit and cyano group-anchored trisubstituted alkenes by utilizing cycloketone oxime esters as C-radical precursors. Both of these reactions have constructed two C-S bonds, and all desired products were obtained in moderate to excellent yields with complete stereospecificity.

17.
Thromb J ; 22(1): 56, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38943162

RESUMEN

BACKGROUND: Hypercoagulability emerges as a central pathological feature and clinical complication in nephrotic syndrome. Increased platelet activation and aggregability are closely related to hypercoagulability in nephrotic syndrome. Monocyte-platelet aggregates (MPAs) have been proposed to represent a robust biomarker of platelet activation. The aim of this study was to investigate levels of the circulating MPAs and MPAs with the different monocyte subsets to evaluate the association of MPAs with hypercoagulability in nephrotic syndrome. METHODS: Thirty-two patients with nephrotic syndrome were enrolled. In addition, thirty-two healthy age and sex matched adult volunteers served as healthy controls. MPAs were identified by CD14 monocytes positive for CD41a platelets. The classical (CD14 + + CD16-, CM), the intermediate (CD14 + + CD16+, IM) and the non-classical (CD14 + CD16++, NCM) monocytes, as well as subset specific MPAs, were measured by flow cytometry. RESULTS: Patients with nephrotic syndrome showed a higher percentage of circulating MPAs as compared with healthy controls (p < 0.001). The percentages of MPAs with CM, IM, and NCM were higher than those of healthy controls (p = 0.012, p < 0.001 and p < 0.001, respectively). Circulating MPAs showed correlations with hypoalbuminemia (r=-0.85; p < 0.001), hypercholesterolemia (r = 0.54; p < 0.001), fibrinogen (r = 0.70; p < 0.001) and D-dimer (r = 0.37; p = 0.003), but not with hypertriglyceridemia in nephrotic syndrome. The AUC for the prediction of hypercoagulability in nephrotic syndrome using MPAs was 0.79 (95% CI 0.68-0.90, p < 0.001). The sensitivity of MPAs in predicting hypercoagulability was 0.71, and the specificity was 0.78. CONCLUSION: Increased MPAs were correlated with hypercoagulability in nephrotic syndrome. MPAs may serve as a potential biomarker for thrombophilic or hypercoagulable state and provide novel insight into the mechanisms of anticoagulation in nephrotic syndrome.

18.
Acta Pharmacol Sin ; 45(5): 959-974, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38225394

RESUMEN

Following acute myocardial ischemia reperfusion (MIR), macrophages infiltrate damaged cardiac tissue and alter their polarization phenotype to respond to acute inflammation and chronic fibrotic remodeling. In this study we investigated the role of macrophages in post-ischemic myocardial fibrosis and explored therapeutic targets for myocardial fibrosis. Male mice were subjected to ligation of the left coronary artery for 30 min. We first detected the levels of chemokines in heart tissue that recruited immune cells infiltrating into the heart, and found that granulocyte-macrophage colony-stimulating factor (GMCSF) released by mouse cardiac microvascular endothelial cells (MCMECs) peaked at 6 h after reperfusion, and c-c motif chemokine ligand 2 (CCL2) released by GMCSF-induced macrophages peaked at 24 h after reperfusion. In co-culture of BMDMs with MCMECs, we demonstrated that GMCSF derived from MCMECs stimulated the release of CCL2 by BMDMs and effectively promoted the migration of BMDMs. We also confirmed that GMCSF promoted M1 polarization of macrophages in vitro, while GMCSF neutralizing antibodies (NTABs) blocked CCL2/CCR2 signaling. In MIR mouse heart, we showed that GMCSF activated CCL2/CCR2 signaling to promote NLRP3/caspase-1/IL-1ß-mediated and amplified inflammatory damage. Knockdown of CC chemokine receptor 2 gene (CCR2-/-), or administration of specific CCR2 inhibitor RS102895 (5 mg/kg per 12 h, i.p., one day before MIR and continuously until the end of the experiment) effectively reduced the area of myocardial infarction, and down-regulated inflammatory mediators and NLRP3/Caspase-1/IL-1ß signaling. Mass cytometry confirmed that M2 macrophages played an important role during fibrosis, while macrophage-depleted mice exhibited significantly reduced transforming growth factor-ß (Tgf-ß) levels in heart tissue after MIR. In co-culture of macrophages with fibroblasts, treatment with recombinant mouse CCL2 stimulated macrophages to release a large amount of Tgf-ß, and promoted the release of Col1α1 by fibroblasts. This effect was diminished in BMDMs from CCR2-/- mice. After knocking out or inhibiting CCR2-gene, the levels of Tgf-ß were significantly reduced, as was the level of myocardial fibrosis, and cardiac function was protected. This study confirms that the acute injury to chronic fibrosis transition after MIR in mice is mediated by GMCSF/CCL2/CCR2 signaling in macrophages through NLRP3 inflammatory cascade and the phenotype switching.


Asunto(s)
Quimiocina CCL2 , Fibrosis , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Macrófagos , Ratones Endogámicos C57BL , Daño por Reperfusión Miocárdica , Fenotipo , Receptores CCR2 , Animales , Receptores CCR2/metabolismo , Receptores CCR2/antagonistas & inhibidores , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Masculino , Quimiocina CCL2/metabolismo , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Ratones , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Miocardio/patología , Miocardio/metabolismo , Transducción de Señal , Células Endoteliales/metabolismo , Células Endoteliales/efectos de los fármacos , Células Cultivadas , Ratones Noqueados
19.
Respiration ; 103(7): 359-367, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38588649

RESUMEN

INTRODUCTION: Endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy (EBUS-TMC), a novel technique, has been reported to improve the diagnostic value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for mediastinal lesions in recent studies. Current literature suggests that this procedure has greater diagnostic efficacy compared to conventional EBUS-TBNA. This systematic review and meta-analysis aimed to evaluate the diagnostic yield and complications associated with EBUS-TMC in comparison to EBUS-TBNA, thereby exploring the potential of this novel technique in enhancing the diagnostic utility for mediastinal lesions. METHODS: A comprehensive literature review was conducted by searching the PubMed, Embase, and Google Scholar databases for articles published from inception to December 31, 2023. The objective of this review was to evaluate the utilization of EBUS-TMC in diagnosing mediastinal disease, while also assessing the quality of each study using the QUADAS-2 tool. The diagnostic yield estimates were subjected to a meta-analysis utilizing inverse variance weighting. Furthermore, a comprehensive analysis of the complications associated with this procedure was performed. RESULTS: The meta-analysis included 10 studies involving a total of 538 patients. The findings of the meta-analysis demonstrated that EBUS-TMC yielded an overall diagnostic rate of 89.59% (482/538), while EBUS-TBNA yielded a rate of 77.13% (415/538). The calculated inverse variance-weighted odds ratio was 2.63 (95% confidence interval, 1.86-3.72; p < 0.0001), and I2 value was 11%, indicating a statistically significant difference between the two techniques. The associated complications consisted of pneumothorax, pneumomediastinum, mediastinitis, and bleeding, with an incidence of 0.74% (4/538), 0.37% (2/538), 0.0% (0/538), and 1.12% (6/538), respectively. Moreover, the funnel plot displayed no discernible publication bias. Further subgroup analysis revealed a notable improvement in the diagnosis value for lymphoma (86.36% vs. 27.27%, p = 0.0006) and benign disorder (87.62% vs. 60.00%, p < 0.0001). CONCLUSION: This review of the current available studies indicated that EBUS-TMC enhanced overall diagnostic yields compared to EBUS-TBNA, particularly for diagnosing benign disease and lymphoma. This procedure was not associated with any serious complications.


Asunto(s)
Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Enfermedades del Mediastino , Humanos , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/efectos adversos , Enfermedades del Mediastino/patología , Enfermedades del Mediastino/diagnóstico , Mediastino/patología , Criocirugía/métodos , Broncoscopía/métodos , Neoplasias del Mediastino/patología , Neoplasias del Mediastino/diagnóstico
20.
BMC Pulm Med ; 24(1): 176, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38609879

RESUMEN

BACKGROUND: Studies have shown that mitochondrial function and macrophages may play a role in the development of idiopathic pulmonary fibrosis (IPF). However, the understanding of the interactions and specific mechanisms between mitochondrial function and macrophages in pulmonary fibrosis is still very limited. METHODS: To construct a prognostic model for IPF based on Macrophage- related genes (MaRGs) and Mitochondria-related genes (MitoRGs), differential analysis was performed to achieve differentially expressed genes (DEGs) between IPF and Control groups in the GSE28042 dataset. Then, MitoRGs, MaRGs and DEGs were overlapped to screen out the signature genes. The univariate Cox analysis and the least absolute shrinkage and selection operator (LASSO) algorithm were implemented to achieve key genes. Furthermore, the independent prognostic analysis was employed. The ingenuity pathway analysis (IPA) was employed to further understand the molecular mechanisms of key genes.Next, the immune infiltration analysis was implemented to identify differential immune cells between two risk subgroups. RESULTS: There were 4791 DEGs between IPF and Control groups. Furthermore, 26 signature genes were achieved by the intersection processing. Three key genes including ALDH2, MCL1, and BCL2A1 were achieved, and the risk model based on the key genes was created. In addition, a nomogram for survival forecasting of IPF patients was created based on riskScore, Age, and Gender, and we found that key genes were associated with classical pathways including 'Apoptosis Signaling', 'PI3K/AKT Signaling', and so on. Next, two differential immune cells including Monocytes and CD8 T cells were identified between two risk subgroups. Moreover, we found that MIR29B2CHG and hsa-mir-1-3p could regulate the expression of ALDH2. CONCLUSION: We achieved 3 key genes including ALDH2, MCL1,, and BCL2A1 associated with IPF, providing a new theoretical basis for clinical treatment of IPF.


Asunto(s)
Fibrosis Pulmonar Idiopática , Fosfatidilinositol 3-Quinasas , Humanos , Pronóstico , Proteína 1 de la Secuencia de Leucemia de Células Mieloides , Macrófagos , ADN Mitocondrial , Fibrosis Pulmonar Idiopática/genética , Mitocondrias/genética , Aldehído Deshidrogenasa Mitocondrial
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