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1.
Front Cardiovasc Med ; 11: 1326897, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38742172

RESUMEN

Objective: Leucine-rich α-2 glycoprotein 1 (LRG1) promotes inflammation and myocardial injury, but its clinical role in ST-elevation myocardial infarction (STEMI) is rarely disclosed. Herein, this prospective study aimed to explore the value of plasma LRG1 at different time points to predict major adverse cardiovascular event (MACE) risk in patients with STEMI. Methods: In total, 209 patients with STEMI were enrolled for determining plasma LRG1 at admission and on day (D)1/D7/D30 after admission via enzyme-linked immunosorbent assay, as well as for determination of peripheral blood T helper 17 (Th17) cells and regulatory T (Treg) cells by flow cytometry. In addition, plasma LRG1 was obtained from 30 healthy controls at enrollment. Results: LRG1 was increased in patients with STEMI at admission compared with healthy controls (P < 0.001). In patients with STEMI, LRG1 varied at different time points (P < 0.001), which elevated from admission to D1, and gradually declined thereafter. LRG1 at admission was positively associated with Th17 cells (P = 0.001) and Th17/Treg ratio (P = 0.014). LRG1 at admission (P = 0.013), D1 (P = 0.034), D7 (P = 0.001), and D30 (P = 0.010) were increased in patients with MACE compared with those without. LRG1 at D7 exhibited good ability to estimate MACE risk (area under curve = 0.750, 95% confidence interval = 0.641-0.858). LRG1 at admission > 60 µg/ml (P = 0.031) and D7 > 60 µg/ml (P = 0.018) were linked with increased accumulating MACE. Importantly, LRG1 at D7 > 60 µg/ml was independently correlated with increased MACE risk (hazard ratio = 5.216, P = 0.033). Conclusion: Plasma LRG1 increases from admission to D1 and gradually declines until D30, which positively links with Th17 cells and MACE risk in patients with STEMI.

2.
Sci Rep ; 14(1): 10899, 2024 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-38740854

RESUMEN

In order to obtain the best mass spectrometry identification results for using the most appropriate methods in clinical practice, we explore the optimal pretreatment methods for different species and morphologies of filamentous fungi. 98 fungal strains were treated with formic acid sandwich method, dispersion method, extraction method, and other methods using a medium element mass spectrometer (EXS3000) as a platform. Each strain had three targets, and the identification rates and confidence differences under different pre-treatment methods were compared to evaluate the identification effects of these methods. The mass spectrometry identification rates of 98 filamentous fungi obtained after pre-treatment with formic acid sandwich method, dispersion method, and extraction method were 85.71%, 82.65%, and 75.51%, respectively. The identification rate of the formic acid sandwich method was significantly higher than the other two methods (P < 0 005) has the best identification ability and the obtained confidence is also higher than the other two methods. The use of formic acid sandwich method for mass spectrometry identification of filamentous fungi can achieve ideal identification results, which is suitable for mass spectrometry identification of filamentous fungi in conventional laboratories.


Asunto(s)
Hongos , Espectrometría de Masas , Hongos/aislamiento & purificación , Hongos/clasificación , Espectrometría de Masas/métodos , Formiatos/química , Formiatos/análisis , Micosis/microbiología , Micosis/diagnóstico , Humanos
3.
Biochem Biophys Res Commun ; 715: 150004, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38678784

RESUMEN

Megakaryopoiesis and platelet production is a complex process that is underpotential regulation at multiple stages. Many long non-coding RNAs (lncRNAs) are distributed in hematopoietic stem cells and platelets. lncRNAs may play important roles as key epigenetic regulators in megakaryocyte differentiation and proplatelet formation. lncRNA NORAD can affect cell ploidy by sequestering PUMILIO proteins, although its direct effect on megakaryocyte differentiation and thrombopoiesis is still unknown. In this study, we demonstrate NORAD RNA is highly expressed in the cytoplasm during megakaryocyte differentiation. Interestingly, we identified for the first time that NORAD has a strong inhibitory effect on megakaryocyte differentiation and proplatelet formation from cultured megakaryocytes. DUSP6/ERK1/2 pathway is activated in response to NORAD knockdown during megakaryocytopoiesis, which is achieved by sequestering PUM2 proteins. Finally, compared with the wild-type control mice, NORAD knockout mice show a faster platelet recovery after severe thrombocytopenia induced by 6 Gy total body irradiation. These findings demonstrate lncRNA NORAD has a key role in regulating megakaryocyte differentiation and thrombopoiesis, which provides a promising molecular target for the treatment of platelet-related diseases such as severe thrombocytopenia.


Asunto(s)
Plaquetas , Diferenciación Celular , Fosfatasa 6 de Especificidad Dual , Megacariocitos , Ratones Noqueados , ARN Largo no Codificante , Trombopoyesis , Megacariocitos/metabolismo , Megacariocitos/citología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Animales , Trombopoyesis/genética , Plaquetas/metabolismo , Ratones , Fosfatasa 6 de Especificidad Dual/metabolismo , Fosfatasa 6 de Especificidad Dual/genética , Sistema de Señalización de MAP Quinasas , Trombocitopenia/genética , Trombocitopenia/metabolismo , Trombocitopenia/patología , Humanos , Ratones Endogámicos C57BL , Células Cultivadas
4.
Nucleic Acids Res ; 52(9): 4969-4984, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38452206

RESUMEN

Proteasome-mediated degradation of chromatin-bound NF-κB is critical in terminating the transcription of pro-inflammatory genes and can be triggered by Set9-mediated lysine methylation of the RelA subunit. However, the E3 ligase targeting methylated RelA remains unknown. Here, we find that two structurally similar substrate-recognizing components of Cullin-RING E3 ligases, WSB1 and WSB2, can recognize chromatin-bound methylated RelA for polyubiquitination and proteasomal degradation. We showed that WSB1/2 negatively regulated a subset of NF-κB target genes via associating with chromatin where they targeted methylated RelA for ubiquitination, facilitating the termination of NF-κB-dependent transcription. WSB1/2 specifically interacted with methylated lysines (K) 314 and 315 of RelA via their N-terminal WD-40 repeat (WDR) domains, thereby promoting ubiquitination of RelA. Computational modeling further revealed that a conserved aspartic acid (D) at position 158 within the WDR domain of WSB2 coordinates K314/K315 of RelA, with a higher affinity when either of the lysines is methylated. Mutation of D158 abolished WSB2's ability to bind to and promote ubiquitination of methylated RelA. Together, our study identifies a novel function and the underlying mechanism for WSB1/2 in degrading chromatin-bound methylated RelA and preventing sustained NF-κB activation, providing potential new targets for therapeutic intervention of NF-κB-mediated inflammatory diseases.


Asunto(s)
Cromatina , Lisina , Complejo de la Endopetidasa Proteasomal , Factor de Transcripción ReIA , Ubiquitinación , Factor de Transcripción ReIA/metabolismo , Lisina/metabolismo , Humanos , Cromatina/metabolismo , Metilación , Complejo de la Endopetidasa Proteasomal/metabolismo , Proteolisis , FN-kappa B/metabolismo , Unión Proteica , Células HEK293 , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética
5.
RSC Adv ; 14(14): 9668-9677, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38525063

RESUMEN

In magnesium-sulfur batteries, electrolyte exploration is vital for developing high-energy-density, safe, and reliable batteries. This study focused on cyclic THF and chain DME, representative solvents in ether electrolytes. MgCl2, an ideal anionic salt, forms mono-nuclear (MgCl2(DME)2), bi-nuclear ([Mg2(µ-Cl)2(DME)4]2+), and tri-nuclear ([Mg3(µ-Cl)4(DME)5]2+) complexes in DME. With increasing salt concentration, these complexes sequentially form. Under lower salt concentrations, THF and MgCl2 form mono-nuclear complexes ([MgCl2(THF)4]) and continue to form bi-nuclear complexes ([Mg2(µ-Cl)3(THF)6]+). However, at higher salt concentrations, bi-nuclear complexes ([Mg2(µ-Cl)3(THF)6]+) directly form in THF. Comparing HOMO-LUMO values, [Mg(DME)3]2+ is easily oxidized. Energy gaps decrease with Cl- ion addition, enhancing solution conductivity. Ratios of Mg2+ and Cl- in S-reduction complexes differ, suggesting DME is better at a low Mg/Cl ratio, and THF at a high Mg/Cl ratio. This study contributes to understanding complexes and enhancing Mg-S battery performance.

6.
ISME J ; 18(1)2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-38531781

RESUMEN

Intestinal microbial disturbance is a direct cause of host disease. The bacterial Type VI secretion system (T6SS) often plays a crucial role in the fitness of pathogenic bacteria by delivering toxic effectors into target cells. However, its impact on the gut microbiota and host pathogenesis is poorly understood. To address this question, we characterized a new T6SS in the pathogenic Aeromonas veronii C4. First, we validated the secretion function of the core machinery of A. veronii C4 T6SS. Second, we found that the pathogenesis and colonization of A. veronii C4 is largely dependent on its T6SS. The effector secretion activity of A. veronii C4 T6SS not only provides an advantage in competition among bacteria in vitro, but also contributes to occupation of an ecological niche in the nutritionally deficient and anaerobic environment of the host intestine. Metagenomic analysis showed that the T6SS directly inhibits or eliminates symbiotic strains from the intestine, resulting in dysregulated gut microbiome homeostasis. In addition, we identified three unknown effectors, Tse1, Tse2, and Tse3, in the T6SS, which contribute to T6SS-mediated bacterial competition and pathogenesis by impairing targeted cell integrity. Our findings highlight that T6SS can remodel the host gut microbiota by intricate interplay between T6SS-mediated bacterial competition and altered host immune responses, which synergistically promote pathogenesis of A. veronii C4. Therefore, this newly characterized T6SS could represent a general interaction mechanism between the host and pathogen, and may offer a potential therapeutic target for controlling bacterial pathogens.


Asunto(s)
Microbioma Gastrointestinal , Sistemas de Secreción Tipo VI , Sistemas de Secreción Tipo VI/genética , Microbioma Gastrointestinal/fisiología , Aeromonas veronii/genética , Simbiosis , Ecosistema , Proteínas Bacterianas/genética
7.
Phytother Res ; 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38526171

RESUMEN

BACKGROUND AND AIM: Although the anti-cancer activity of isoalantolactone (IATL) has been extensively studied, the anti-melanoma effects of IATL are still unknown. Here, we have investigated the anti-melanoma effects and mechanism of action of IATL. MTT and crystal violet staining assays were performed to detect the inhibitory effect of IATL on melanoma cell viability. Apoptosis and cell cycle arrest induced by IATL were examined using flow cytometry. The molecular mechanism of IATL was explored by Western blotting, confocal microscope analysis, molecular docking, and cellular thermal shift assay (CETSA). A B16F10 allograft mouse model was constructed to determine the anti-melanoma effects of IATL in vivo. The results showed that IATL exerted anti-melanoma effects in vitro and in vivo. IATL induced cytoprotective autophagy in melanoma cells by inhibiting the PI3K/AKT/mTOR signaling. Moreover, IATL inhibited STAT3 activation both in melanoma cells and allograft tumors not only by binding to the SH2 domain of STAT3 but also by suppressing the activity of its upstream kinase Src. These findings demonstrate that IATL exerts anti-melanoma effects via inhibiting the STAT3 and PI3K/AKT/mTOR signaling pathways, and provides a pharmacological basis for developing IATL as a novel phytotherapeutic agent for treating melanoma clinically.

8.
Comput Biol Med ; 172: 108265, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38461698

RESUMEN

Convolution operation is performed within a local window of the input image. Therefore, convolutional neural network (CNN) is skilled in obtaining local information. Meanwhile, the self-attention (SA) mechanism extracts features by calculating the correlation between tokens from all positions in the image, which has advantage in obtaining global information. Therefore, the two modules can complement each other to improve feature extraction ability. An effective fusion method is a problem worthy of further study. In this paper, we propose a CNN and SA paralleling network CSAP-UNet with U-Net as backbone. The encoder consists of two parallel branches of CNN and Transformer to extract the feature from the input image, which takes into account both the global dependencies and the local information. Because medical images come from certain frequency bands within the spectrum, their color channels are not as uniform as natural images. Meanwhile, medical segmentation pays more attention to lesion regions in the image. Attention fusion module (AFM) integrates channel attention and spatial attention in series to fuse the output features of the two branches. The medical image segmentation task is essentially to locate the boundary of the object in the image. The boundary enhancement module (BEM) is designed in the shallow layer of the proposed network to focus more specifically on pixel-level edge details. Experimental results on three public datasets validate that CSAP-UNet outperforms state-of-the-art networks, particularly on the ISIC 2017 dataset. The cross-dataset evaluation on Kvasir and CVC-ClinicDB shows that CSAP-UNet has strong generalization ability. Ablation experiments also indicate the effectiveness of the designed modules. The code for training and test is available at https://github.com/zhouzhou1201/CSAP-UNet.git.


Asunto(s)
Procesamiento de Imagen Asistido por Computador , Redes Neurales de la Computación
9.
Nanomaterials (Basel) ; 14(1)2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38202557

RESUMEN

Ammonia (NH3) is vital in modern agriculture and industry as a potential energy carrier. The electrocatalytic reduction of nitrate (NO3-) to ammonia under ambient conditions offers a sustainable alternative to the energy-intensive Haber-Bosch process. However, achieving high selectivity in this conversion poses significant challenges due to the multi-step electron and proton transfer processes and the low proton adsorption capacity of transition metal electrocatalysts. Herein, we introduce a novel approach by employing functionalized multi-walled carbon nanotubes (MWCNTs) as carriers for active cobalt catalysts. The exceptional conductivity of MWCNTs significantly reduces charge transfer resistance. Their unique hollow structure increases the electrochemical active surface area of the electrocatalyst. Additionally, the one-dimensional hollow tube structure and graphite-like layers within MWCNTs enhance adsorption properties, thus mitigating the diffusion of intermediate and stabilizing active cobalt species during nitrate reduction reaction (NitRR). Using the MWCNT-supported cobalt catalyst, we achieved a notable NH3 yield rate of 4.03 mg h-1 cm-2 and a high Faradaic efficiency of 84.72% in 0.1 M KOH with 0.1 M NO3-. This study demonstrates the potential of MWCNTs as advanced carriers in constructing electrocatalysts for efficient nitrate reduction.

10.
Angew Chem Int Ed Engl ; 63(3): e202317622, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38061991

RESUMEN

Simultaneous optimization of the energy level of water dissociation, hydrogen and hydroxide desorption is the key to achieving fast kinetics for the alkaline hydrogen evolution reaction (HER). Herein, the well-dispersed Ru clusters on the surface of amorphous/crystalline CeO2-δ (Ru/ac-CeO2-δ ) is demonstrated to be an excellent electrocatalyst for significantly boosting the alkaline HER kinetics owing to the presence of unique oxygen vacancy (VO ) and Ru Lewis acid-base pairs (LABPs). The representative Ru/ac-CeO2-δ exhibits an outstanding mass activity of 7180 mA mgRu -1 that is approximately 9 times higher than that of commercial Pt/C at the potential of -0.1 V (V vs RHE) and an extremely low overpotential of 21.2 mV at a geometric current density of 10 mA cm-2 . Experimental and theoretical studies reveal that the VO as Lewis acid sites facilitate the adsorption of H2 O and cleavage of H-OH bonds, meanwhile, the weak Lewis basic Ru clusters favor for the hydrogen desorption. Importantly, the desorption of OH from VO sites is accelerated via a water-assisted proton exchange pathway, and thus boost the kinetics of alkaline HER. This study sheds new light on the design of high-efficiency electrocatalysts with LABPs for the enhanced alkaline HER.

11.
Dalton Trans ; 53(1): 162-170, 2023 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-38018516

RESUMEN

The energy-intensive processes for the industrial production of ammonia necessitates the development of new methods to be proposed that will aid in reducing the global energy consumption. Specifically, the electrocatalytic nitrate reduction reaction (NO3RR) to produce ammonia is more thermodynamically feasible than the electrocatalytic nitrogen reduction reaction (NRR). However, it is hindered by a low catalytic activity due to its complex reaction pathways. Herein, we synthesized a novel electrocatalyst, RuOx-Co3O4 nanoparticles, with abundant interfaces, which exhibited an enhanced catalytic activity for efficient ammonia synthesis. This catalyst delivered a partial current density of 65.8 mA cm-2 for NH3 production, a faradaic efficiency (FE) of 89.7%, and a superior ammonia yield rate of up to 210.5 µmol h-1 cm-2 at -0.6 V vs. RHE. X-ray photoelectron and Raman spectroscopy revealed that the formed interfacial Ru-O-Co bond can decorate the electronic structures of the active sites and accelerate the absorption of NO3-, thus promoting the production of ammonia.

12.
Nanoscale ; 15(44): 17793-17807, 2023 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-37916998

RESUMEN

Superhydrophobic surfaces have attracted broad attention because of their unique water repellency but are restricted by poor wear resistance, weak adhesion to the substrate, and complex fabrication processes. Herein, a double-layer coating strategy consisting of the amino fluorine-silicone resin/epoxy resin (AFSR/EP) system is created. The system features a high hardness and transparent hydrophobic interface adhesive layer through the amine-epoxy "click" chemical reaction. The environmentally friendly resin system and low-cost nano-silica particles (n-SiO2) are composited and sprayed onto the substrate surface to form a superhydrophobic layer with outstanding robustness and excellent environmental stability. The prepared AFSR/EP@n-SiO2 composite coatings have a water contact angle of 161.1° and a sliding angle of 3.4°, demonstrating high superhydrophobic properties. Benefitting from the complementary advantages of silicone/epoxy resin, the prepared composite coatings maintain remarkable water repellency after various harsh environmental tests, including cyclic mechanical abrasion and tape-stripping, acid-base (pH 1 and pH 14) treatment, 10 wt% NaCl (pH 7) salt solution immersion, temperature treatment, knife scratching, and long-term ultraviolet radiation treatment, showing reinforced mechanical robustness and durable anti-corrosion stability. Notably, surface hardness of 5H and optical transparency over 80% can be achieved. The simple method offers a novel approach for the large-scale preparation of multifunctional superhydrophobic coatings.

13.
Curr Med Sci ; 43(6): 1201-1205, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37848750

RESUMEN

OBJECTIVE: Lipopolysaccharide-induced tumor necrosis factor-α factor (LITAF) protein is a newly discovered inflammatory protein. This study aims to study the role of LITAF in the formation of atherosclerosis. METHODS: A total of 10 C57BL/6J mice and 10 C57BL/6J mice with knockout of LITAF gene (C57BL/6J-LITAF-) were divided into two groups: the control group and the LITAF-/- group. The animals were accommodated for 16 weeks and then euthanized with their hearts and aortas isolated thereafter. Next, the roots of the mouse aorta were cryosectioned and stained with Oil Red O staining and immunohistochemical staining (CD68, α-SMA, and Masson), respectively. The area of Oil Red O staining and the proportion of positive expression after immunohistochemical staining were then compared between the control and LITAF-/- groups. At the same time, the blood of mice was collected for the extraction of proteins and RNA. The proteins and RNA were used to detect the expression of major molecules of the NF-κB inflammatory pathway in mice in the control group and the LITAF-/- group by Western blotting and RT-PCR. RESULTS: Oil Red O staining of the aortic root sections of the mice in each group revealed that the area of atherosclerotic plaques in the LITAF-/- group was substantially lower than that in the control group (P<0.05). Moreover, immunohistochemical staining determined that the expression level of α-SMA and CD68 in the LITAF-/- group was significantly lower than that in the control group, whereas the results were reversed following Masson staining (P<0.05). The expression levels of P65 and caspase 3 were significantly lower in the LITAF-/- group than in the control group (P<0.05), whereas the expression level of IκB was higher in the LITAF-/- group. CONCLUSION: LITAF might participate in the formation of atherosclerotic plaque through the NF-κB pathway and play a promoting role in the formation of atherosclerosis.


Asunto(s)
Aterosclerosis , Placa Aterosclerótica , Animales , Ratones , Aterosclerosis/metabolismo , Lipopolisacáridos , Ratones Endogámicos C57BL , FN-kappa B/genética , FN-kappa B/metabolismo , Placa Aterosclerótica/genética , Placa Aterosclerótica/patología , ARN , Transducción de Señal , Factor de Necrosis Tumoral alfa
14.
Nanomicro Lett ; 15(1): 166, 2023 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-37394676

RESUMEN

Molybdenum carbide (Mo2C) materials are promising electrocatalysts with potential applications in hydrogen evolution reaction (HER) due to low cost and Pt-like electronic structures. Nevertheless, their HER activity is usually hindered by the strong hydrogen binding energy. Moreover, the lack of water-cleaving sites makes it difficult for the catalysts to work in alkaline solutions. Here, we designed and synthesized a B and N dual-doped carbon layer that encapsulated on Mo2C nanocrystals (Mo2C@BNC) for accelerating HER under alkaline condition. The electronic interactions between the Mo2C nanocrystals and the multiple-doped carbon layer endow a near-zero H adsorption Gibbs free energy on the defective C atoms over the carbon shell. Meanwhile, the introduced B atoms afford optimal H2O adsorption sites for the water-cleaving step. Accordingly, the dual-doped Mo2C catalyst with synergistic effect of non-metal sites delivers superior HER performances of a low overpotential (99 mV@10 mA cm-2) and a small Tafel slope (58.1 mV dec-1) in 1 M KOH solution. Furthermore, it presents a remarkable activity that outperforming the commercial 10% Pt/C catalyst at large current density, demonstrating its applicability in industrial water splitting. This study provides a reasonable design strategy towards noble-metal-free HER catalysts with high activity.

15.
RSC Adv ; 13(30): 20926-20933, 2023 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-37441038

RESUMEN

Because of the abundance of magnesium and sulfur and their low cost, the development of magnesium sulfur batteries is very promising. In particular, the battery performance of nanoscale (MgS)n clusters is much better than that of bulk sized MgS. However, the structures, stability, and properties of MgxSy and (MgS)n clusters, which are very important to improve the performance of Mg-S batteries, are still unexplored. Herein, the most stable structures of MgxSy (x = 1-8, y = 1-8) and (MgS)n (n = 1-10) are reliably determined using the structure search method and density functional theory to calculate. According to calculation results, MgS3 and Mg6S8 may not exist in the actual charging and discharging products of magnesium sulfide batteries. The (MgS)n (n ≥ 5) clusters exhibit intriguing cage-like structures, which are favorable for eliminating dangling bonds and enhancing structural stability. Compared to the MgS monomer, each sulfur atom in the clusters is coordinated with more magnesium atoms, thus lengthening the Mg-S bond length and decreasing the Mg-S bond activation energy. Notably, with the increase of dielectric constant of electrolyte solvent, compared to the DME (ε = 7.2), THF (ε = 7.6) and C2H4Cl2 (ε = 10.0), MgxSy and (MgS)n clusters are most stable in the environment of C3H6O (ε = 20.7). It can delay the transformation of magnesium polysulfide to the final product MgS, which is conducive to improving the performance of Mg-S batteries. The predicted characteristic peaks of infrared and Raman spectra provide useful information for in situ experimental investigation. Our work represents a significant step towards understanding (MgS)n clusters and improving the performance of Mg-S batteries.

16.
Sci China Life Sci ; 66(11): 2527-2542, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37428305

RESUMEN

Alveolar macrophages (AMs) are self-maintained immune cells that play vital roles in lung homeostasis and immunity. Although reporter mice and culture systems have been established for studying macrophages, an accurate and specific reporter line for alveolar macrophage study is still not available. Here we reported a novel Rspo1-tdTomato gene reporter mouse line that could specifically label mouse AMs in a cell-intrinsic manner. Using this reporter system, we visualized the dynamics of alveolar macrophages intravitally under steady state and characterized the alveolar macrophage differentiation under in vitro condition. By performing ATAC-seq, we found that insertion of the tdTomato cassette in the Rspo1 locus increased the accessibility of a PPARE motif within the Rspo1 locus and revealed a potential regulation by key transcription factor PPAR-γ for alveolar macrophage differentiation in vitro and in vivo. Consistently, perturbation of PPAR-γ by its agonist rosiglitazone or inhibitor GW9662 resulted in corresponding alteration of tdTomato expression in alveolar macrophages together with the transcription of PPAR-γ downstream target genes. Furthermore, global transcriptomic analyses of AMs from the wild type mice and the Rspo1-tdTomato mice showed comparable gene expression profiles, especially those AM-specific genes, confirming that the insertion of the tdTomato cassette in the Rspo1 locus does not impact the cell identity and biological function of AMs under normal condition. Taken together, our study provides an alternative tool for in vivo and in vitro labeling of alveolar macrophages with high specificity which could also be utilized as an indicator of PPAR-γ activity for future development of PPAR-γ specific targeting drugs.


Asunto(s)
Pulmón , Macrófagos Alveolares , Ratones , Animales , Macrófagos Alveolares/metabolismo , Pulmón/metabolismo , Macrófagos/metabolismo , Regulación de la Expresión Génica , PPAR gamma/genética , PPAR gamma/metabolismo
17.
Angew Chem Int Ed Engl ; 62(33): e202307848, 2023 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-37378584

RESUMEN

The site isolation strategy has been employed in thermal catalytic acetylene semihydrogenation to inhibit overhydrogenation and C-C coupling. However, there is a dearth of analogous investigations in electrocatalytic systems. In this work, density functional theory (DFT) simulations demonstrate that isolated Cu metal sites have higher energy barriers on overhydrogenation and C-C coupling. Following this result, we develop Cu single-atom catalysts highly dispersed on nitrogen-doped carbon matrix, which exhibit high ethylene selectivity (>80 % Faradaic efficiency for ethylene, <1 % Faradaic efficiency for C4 , and no ethane) at high concentrations of acetylene. The superior performance observed in the electrocatalytic selective hydrogenation of acetylene can be attributed to the weak adsorption of ethylene intermediates and highly energy barriers on C-C coupling at isolated sites, as confirmed by both DFT calculations and experimental results. This study provides a comprehensive understanding of the isolated sites inhibiting the side reactions of electrocatalytic acetylene semihydrogenation.

18.
Adv Sci (Weinh) ; 10(22): e2301834, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37211707

RESUMEN

Cigarettes, despite being economically important legal consumer products, are highly addictive and harmful, particularly to the respiratory system. Tobacco smoke is a complex mixture containing over 7000 chemical compounds, 86 of which are identified to have "sufficient evidence of carcinogenicity" in either animal or human tests. Thus, tobacco smoke poses a significant health risk to humans. This article focuses on materials that help reduce the levels of major carcinogens in cigarette smoke; these include nicotine, polycyclic aromatic hydrocarbons, tobacco-specific nitrosamines, hydrogen cyanide, carbon monoxide, and formaldehyde. Specifically, the research progress on adsorption effects and mechanisms of advanced materials such as cellulose, zeolite, activated carbon, graphene, and molecularly imprinted polymers are highlighted. The future trends and prospects in this field are also discussed. Notably, with advancements in supramolecular chemistry and materials engineering, the design of functionally oriented materials has become increasingly multidisciplinary. Certainly, several advanced materials can play a critical role in reducing the harmful effects of cigarette smoke. This review aims to serve as an insightful reference for the design of hybrid and functionally oriented advanced materials.


Asunto(s)
Fumar Cigarrillos , Contaminación por Humo de Tabaco , Humanos , Contaminación por Humo de Tabaco/análisis , Adsorción , Carcinógenos/análisis
19.
Nanomaterials (Basel) ; 13(8)2023 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-37110884

RESUMEN

Biochar is considered as a promising candidate for emerging sustainable energy systems and environmental technology applications. However, the improvement of mechanical properties remains challenges. Herein, we propose a generic strategy to enhance the mechanical properties of bio-based carbon materials through inorganic skeleton reinforcement. As a proof-of-concept, silane, geopolymer, and inorganic gel are selected as precursors. The composites' structures are characterized and an inorganic skeleton reinforcement mechanism is elucidated. Specifically, two types of reinforcement of the silicon-oxygen skeleton network formed in situ with biomass pyrolysis and the silica-oxy-al-oxy network are constructed to improve the mechanical properties. A significant improvement in mechanical strength was achieved for bio-based carbon materials. The compressive strength of well-balanced porous carbon materials modified by silane can reach up to 88.9 kPa, geopolymer-modified carbon material exhibits an enhanced compressive strength of 36.8 kPa, and that of inorganic-gel-polymer-modified carbon material is 124.6 kPa. Moreover, the prepared carbon materials with enhanced mechanical properties show excellent adsorption performance and high reusability for organic pollutant model compound methylene blue dye. This work demonstrates a promising and universal strategy for enhancing the mechanical properties of biomass-derived porous carbon materials.

20.
J Ethnopharmacol ; 312: 116548, 2023 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-37100264

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Hepatocellular carcinoma (HCC) poses a growing challenge to global health efforts. The 5-year survival rate of HCC patients is still dismal. A traditional prescription Qi-Wei-Wan (QWW) comprising Astragali Radix and Schisandra chinensis Fructus has traditionally been used for HCC treatment according to traditional Chinese medicine theory, but the pharmacological basis is not clear. AIM OF THE STUDY: This study aims to investigate the anti-HCC effects of an ethanolic extract of QWW (hereafter, QWWE) and the mechanism of action. MATERIALS AND METHODS: An UPLC-Q-TOF-MS/MS method was developed to control the quality of QWWE. Two human HCC cell lines (HCCLM3 and HepG2) and a HCCLM3 xenograft mouse model were employed to investigate the anti-HCC effects of QWWE. The anti-proliferative effect of QWWE in vitro was determined by MTT, colony formation and EdU staining assays. Apoptosis and protein levels were examined by flow cytometry and Western blotting, respectively. Nuclear presence of signal transducer and activator of transcription 3 (STAT3) was examined by immunostaining. Transient transfection of pEGFP-LC3 and STAT3C plasmids was performed to assess autophagy and determine the involvement of STAT3 signaling in QWWE's anti-HCC effects, respectively. RESULTS: We found that QWWE inhibited the proliferation of and triggered apoptosis in HCC cells. Mechanistically, QWWE inhibited the activation of SRC and STAT3 at Tyr416 and Tyr705, respectively; inhibited the nuclear translocation of STAT3; lowered Bcl-2 protein levels, while increased Bax protein levels in HCC cells. Over-activating STAT3 attenuated the cytotoxic and apoptotic effects of QWWE in HCC cells. Moreover, QWWE induced autophagy in HCC cells by inhibiting mTOR signaling. Blocking autophagy with autophagy inhibitors (3-methyladenine and chloroquine) enhanced the cytotoxicity, apoptotic effect and the inhibitory effect on STAT3 activation of QWWE. Intragastric administration of QWWE at 10 mg/kg and 20 mg/kg potently repressed tumor growth and inhibited STAT3 and mTOR signaling in tumor tissues, but did not significantly affect mouse body weight. CONCLUSION: QWWE exhibited potent anti-HCC effects. Inhibiting the STAT3 signaling pathway is involved in QWWE-mediated apoptosis, while blocking mTOR signaling contributes to QWWE-mediated autophagy induction. Blockade of autophagy enhanced the anti-HCC effects of QWWE, indicating that the combination of an autophagy inhibitor and QWWE might be a promising therapeutic strategy for HCC management. Our findings provide pharmacological justifications for the traditional use of QWW in treating HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Schisandra , Humanos , Animales , Ratones , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Línea Celular Tumoral , Espectrometría de Masas en Tándem , Apoptosis , Serina-Treonina Quinasas TOR/metabolismo , Autofagia , Proliferación Celular
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