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Recombinant human bone morphogenetic protein 2 (rhBMP-2) is an FDA-approved growth factor for bone regeneration and repair in medical practice. The therapeutic effects of rhBMP-2 may be enhanced through specific binding to extracellular matrix (ECM)-like scaffolds. Here, we report the selection of a novel rhBMP-2-specific DNA aptamer, functionalization of the aptamer in an ECM-like scaffold, and its application in a cellular context. A DNA aptamer BA1 was evolved and shown to have high affinity and specificity to rhBMP-2. A molecular docking model demonstrated that BA1 was probably bound to rhBMP-2 at its heparin-binding domain, as verified with experimental competitive binding assays. The BA1 aptamer was used to functionalize a type I collagen scaffold, and fraction ratios were optimized to mimic the natural ECM. Studies in the myoblast cell model C2C12 showed that the aptamer-enhanced scaffold could specifically augment the osteo-inductive function of rhBMP-2 in vitro. This aptamer-functionalized scaffold may have value in enhancing rhBMP-2-mediated bone regeneration.
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Aptámeros de Nucleótidos , Proteína Morfogenética Ósea 2 , Humanos , Proteína Morfogenética Ósea 2/farmacología , Proteína Morfogenética Ósea 2/química , Aptámeros de Nucleótidos/farmacología , Andamios del Tejido/química , Simulación del Acoplamiento Molecular , Regeneración Ósea , Factor de Crecimiento Transformador beta/farmacología , Proteínas Recombinantes/químicaRESUMEN
Defects on metal oxide have attracted extensive attention in photo-/electrocatalytic CO2 reduction. Herein, porous MgO nanosheets with abundant oxygen vacancies (Vo s) and three-coordinated oxygen atoms (O3c ) at corners are reported, which reconstruct into defective MgCO3 ·3H2 O exposing rich surface unsaturated -OH groups and vacancies to initiate photocatalytic CO2 reduction to CO and CH4 . In consecutive 7-cycle tests (each run for 6 h) in pure water, CO2 conversion keeps stable. The total production of CH4 and CO attains ≈367 µmol gcata -1 h-1 . The selectivity of CH4 gradually increases from ≈3.1% (1st run) to ≈24.5% (4th run) and then remains unchanged under UV-light irradiation. With triethanolamine (3.3 vol.%) as the sacrificial agent, the total production of CO and CH4 production rapidly increases to ≈28â¯000 µmol gcata -1 in 2 h reaction. Photoluminescence spectra reveal that Vo s induces the formation of donor bands to promote charge carrier seperation. A series of trace spectra and theoretical analysis indicate Mg-Vo sites in the derived MgCO3 ·3H2 O are active centers, which play a crucial role in modulating CO2 adsorption and triggering photoreduction reactions. These intriguing results on defective alkaline earth oxides as potential photocatalysts in CO2 conversion may spur some exciting and novel findings in this field.
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DNAzymes have been limited in application by their low catalytic rates. Here, we evolved a new peroxidase DNAzyme mSBDZ-X-3 through a directed evolution method based on the capture of self-biotinylated DNA catalyzed by its intrinsic peroxidase activity. The mSBDX-X-3 DNAzyme has a parallel G-quadruplex structure and has more favorable catalytic properties than all previously reported peroxidase DNAzyme variants. We applied mSBDZ-X-3 in an aptamer-coupled proximity-based labeling proteomic assay to determine the proteins that bind to cell surface cancer biomarkers EpCAM and nucleolin. Confocal microscopy, western blot analysis, and LC-MS/MS showed that the hybrid DNAzyme aptamer-coupled proximity assay-labeled proteins associated with EpCAM and nucleolin within 6-12 min in fixed cancer cells. The labeled proteins were identified by mass spectrometry. This study provides a highly efficient peroxidase DNAzyme, a methodology for selection of such variants, and a method for its application in spatial proteomics using entirely nucleic acid-based tooling.
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Aptámeros de Nucleótidos , Técnicas Biosensibles , ADN Catalítico , G-Cuádruplex , ADN Catalítico/química , Peroxidasa/metabolismo , Molécula de Adhesión Celular Epitelial , Cromatografía Liquida , Proteómica , Espectrometría de Masas en Tándem , Peroxidasas/química , Colorantes , Aptámeros de Nucleótidos/química , Hemina/química , Técnicas Biosensibles/métodosRESUMEN
Background: Human wellbeing has been linked with lifestyle factors such as physical activity, diet balance, sleep quality, depression, and anxiety. However, few studies illustrate the relationship between such lifestyle factors and HPV infection. In this study, we investigated the association between lifestyle factors, age, disease status and HPV infection. Participants and methods: Participants were recruited through a digital eHealth platform in Shenzhen, Mainland China. Both lifestyle factors and cervicovaginal mucus (CVM) samples to test for HPV outcomes were collected from each participant as a cross-sectional study. In addition, the eHealth platform recorded age and current or history diseases, which were adjusted to apply for both univariable and multivariable logistic regression. Furthermore, lifestyle factors were categorized as different levels to conduct stratification analysis. Results: We recruited 149 HPV positive and 346 HPV negative participants through HPV detection. Physical activity and diet balance were significantly associated with HPV infection in lifestyle factors (P values < 0.001) after adjusting for age and current or history diseases. However, stratified analysis showed three factors were insignificant for HPV infection - namely, sleep quality, depression, and anxiety. Most HPV infections involved a sole HPV serotype (83%), and diet balance was the most significant difference between sole and multiple HPV infections. Conclusions: Among lifestyle factors, physical inactivity or diet imbalance can significantly increase HPV infection risk. In particular, diet balance might be related to the number of HPV serotypes. Our results suggest that exercising and regulating diet may reduce the risk of HPV infection.
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Vaginal microbiota (VMB) is associated with changes in Human papilloma virus (HPV) status, which consequently influences the risk of cervical cancer. This association was often confounded by personal risk factors. This pilot research aimed to explore the relationship between vaginal microbiota, personal risk factors and their interactions with HPV status conversion to identify the vaginal microbiota that was associated with HPV clearance under heterogeneous personal risk factors. A total of 38 women participated by self-collecting a cervicovaginal mucus (CVM) sample that was sent for metagenomics sequencing. Most of the participants also filled in personal risk factors questionnaire through an eHealth platform and authorized the use of their previous HPV genotyping results stored in this eHealth platform. Based on the two HPV results, the participants were grouped into three cohorts, namely HPV negative, HPV persistent infection, and HPV status conversion. The relative abundance of VMB and personal factors were compared among these three cohorts. A correlation investigation was performed between VMB and the significant personal factors to characterize a robustness of the panel for HPV status change using R programming. At baseline, 12 participants were HPV-negative, and 22 were HPV-positive. Within one year, 18 women remained HPV-positive, 12 were HPV-negative and 4 participants showed HPV clearance. The factors in the eHealth questionnaire were systematically evaluated which identified several factors significantly associated with persistent HPV infection, including age, salary, history of reproductive tract infection, and the total number of sexual partners. Concurrent vaginal microbiome samples suggest that a candidate biomarker panel consisting of Lactobacillus gasseri, Streptococcus agalactiae, and Timona prevotella bacteria, which may be associated with HPV clearance. This pilot study indicates a stable HPV status-related vaginal microbe environment. To establish a robust biomarker panel for clinical use, larger cohorts will be recruited into follow-up studies.
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Alphapapillomavirus , Microbiota , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Femenino , Humanos , Papillomaviridae/genética , Proyectos Piloto , ARN Ribosómico 16S/genética , Factores de Riesgo , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/microbiología , Neoplasias del Cuello Uterino/prevención & control , Vagina/microbiologíaRESUMEN
Several leukocyte to high-density lipoprotein cholesterol (HDL-C) ratios, including monocyte to HDL-C ratio (MHR), neutrophil to HDL-C ratio (NHR) and lymphocyte to HDL-C ratio (LHR), have been proposed as novel inflammatory indicators. We performed a cross-sectional study to investigate the relationships between these leukocyte to HDL-C ratios and coronary artery disease (CAD) in patients with chest pain with controlled low-density lipoprotein cholesterol (LDL-C). A total of 3482 patients with chest pain with LDL-C <1.8 mmol/L were enrolled. We evaluated the relationships between MHR, NHR, LHR and HDL-C and the occurrence of CAD as well as severe stenosis. We found that in patients with chest pain, higher MHR (adjusted OR=2.83, 95% CI 1.61 to 4.99, p<0.001) and NHR (adjusted OR=1.08, 95% CI 1.04 to 1.13, p<0.001), as well as lower HDL-C (adjusted OR=0.53, 95% CI 0.36 to 0.78, p=0.001), but not higher LHR (adjusted OR=1.06, 95% CI 0.94 to 1.20, p=0.341), had a stronger association with the occurrence of CAD. Moreover, unlike LHR (adjusted OR=1.02, 95% CI 0.93 to 1.13, p=0.654), higher MHR (adjusted OR=2.10, 95% CI 1.43 to 3.07, p<0.001) and NHR (adjusted OR=1.06, 95% CI 1.04 to 1.09, p<0.001) and lower HDL-C (adjusted OR=0.38, 95% CI 0.26 to 0.56, p<0.001) were risk factors for severe stenosis. A receiver operating characteristic curve analysis exhibited comparable abilities between MHR and NHR in predicting the presence and severity of CAD. In conclusion, even though patients with chest pain have achieved LDL-C <1.8 mmol/L, the inflammatory indicators MHR and NHR maintained their predictive abilities and remained associated with the occurrence and severity of CAD.
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Enfermedad de la Arteria Coronaria , Dolor en el Pecho/complicaciones , HDL-Colesterol , LDL-Colesterol , Constricción Patológica , Enfermedad de la Arteria Coronaria/complicaciones , Estudios Transversales , Humanos , Monocitos , Factores de RiesgoRESUMEN
There is a critical need for the development of more potent inhibitors for osteoarthritis (OA) therapy given the poor life quality of arthritis patients. Aggrecanase ADAMTS-5 (a disintegrin and metalloproteinase with thrombospondin motifs 5) is an established drug target identified for osteoarthritis. In this study, we evolved and characterized two new DNA aptamer inhibitors of ADAMTS-5, namely apt21 and apt25. The aptamers exhibited nanomolar binding affinity and high specificity against ADAMTS-5. KD values of apt21 and apt25 were determined by the Enzyme-linked Oligonucleotide Assay (ELONA) at 1.54 ± 0.16 nM and 1.79 ± 0.08 nM, respectively. Circular Dichroism (CD) analysis demonstrated that both aptamers formed monovalent cation dependent G-quadruplex structures. Calcium ions did not affect the binding of the aptamers to ADAMTS-5. The inhibitory effects of apt21 and apt25 on ADAMTS-5 were evaluated by the Förster Resonance Energy Transfer (FRET) assay, in which IC50 values of apt21 and apt25 were estimated at 52.76 ± 6.70 µM and 61.14 ± 9.67 µM, respectively. These two aptamers are the first DNA G-quadruplex aptamers demonstrated to inhibit ADAMTS-5 and could have value for OA therapy.
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Aptámeros de Nucleótidos , Osteoartritis , Proteína ADAMTS4/química , Proteína ADAMTS4/genética , Proteína ADAMTS4/metabolismo , Proteína ADAMTS5/genética , Proteína ADAMTS5/metabolismo , Aptámeros de Nucleótidos/farmacología , Calcio , Cationes Monovalentes , ADN , Desintegrinas , Humanos , Osteoartritis/tratamiento farmacológico , TrombospondinasRESUMEN
A wide variety of nanomaterials have emerged in recent years with advantageous properties for a plethora of therapeutic and diagnostic applications. Such applications include drug delivery, imaging, anti-cancer therapy and radiotherapy. There is a critical need for further components which can facilitate therapeutic targeting, augment their physicochemical properties, or broaden their theranostic applications. Aptamers are single-stranded nucleic acids which have been selected or evolved to bind specifically to molecules, surfaces, or cells. Aptamers can also act as direct biologic therapeutics, or in imaging and diagnostics. There is a rich field of discovery at the interdisciplinary interface between nanomaterials and aptamer science that has significant potential across biomedicine. Herein, we review recent progress in aptamer-enabled materials and discuss pending challenges for their future biomedical application.
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Aptámeros de Nucleótidos/uso terapéutico , Sistemas de Liberación de Medicamentos/métodos , Nanoestructuras/uso terapéutico , Neoplasias/tratamiento farmacológico , Aptámeros de Nucleótidos/farmacología , HumanosRESUMEN
It is reported that LGR4 (leucine-rich repeat domain containing G protein-coupled receptor 4) plays a crucial role in the physiological function of many organs. However, few data are available on the function and mechanism of LGR4 in myocardial ischemia-reperfusion (I/R) injury. The aim of this study was to explore the function and mechanism of LGR4 in I/R injury. We incubated H9c2 cells in simulating ischemia buffer and then re-incubated them in normal culture medium to establish a model of I/R injury in vitro. The expression of LGR4 was evaluated by RT-PCR and western blot. Besides, the cell apoptosis was evaluated by flow cytometric analysis and the content of ROS, SOD, MDA, LDH, CK, ATP, cyt c were detected by special commercial kits. The expression of mitochondrial function-related proteins were detected by western blot. Then, the roles of ERK signaling pathway was determined with TBHQ (ERK activator) treatment. Our data have demonstrated that I/R boosted the expression of LGR4 in H9c2 cells. Knockdown of LGR4 increased the apoptosis rate of H9c2 cells and led to excessed oxidant stress and impaired mitochondrial function by increasing the levels of ROS, MDA, LDH, CK and cyt c and inhibiting SOD activity, ATP production. In addition, LGR4 silence inhibited the activation of ERK pathway. And TBHQ partially reversed the effects of LGR4 knockdown on H9c2 cells. To conclude, our study indicated that LGR4 regulated mitochondrial dysfunction and oxidative stress by ERK signaling pathways, which provides a potential cardiac protective target against I/R.
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Daño por Reperfusión Miocárdica/metabolismo , Miocitos Cardíacos/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Apoptosis/genética , Apoptosis/fisiología , Línea Celular , Supervivencia Celular/genética , Supervivencia Celular/fisiología , Citometría de Flujo , Humanos , Sistema de Señalización de MAP Quinasas/genética , Sistema de Señalización de MAP Quinasas/fisiología , Mitocondrias/metabolismo , Daño por Reperfusión Miocárdica/genética , Estrés Oxidativo/genética , Estrés Oxidativo/fisiología , Receptores Acoplados a Proteínas G/deficiencia , Receptores Acoplados a Proteínas G/genética , Transducción de Señal/genética , Transducción de Señal/fisiologíaRESUMEN
The effects of interferon-γ (IFN-γ) on cholesterol accumulation and the development of foam cells are still unclear. In the present study, we found that IFN-γ promoted liver X receptor (LXR)-α degradation through the ubiquitin-proteasome system in macrophages. The process was dependent on its interactions with phosphorylated signal transducer and activator of transcription 1 (p-STAT1) and protein inhibitor of activated STAT 1 (PIAS1) because both fludarabine and PIAS1 shRNA reversed the decrease in LXR-α protein expression induced by IFN-γ. Additionally, IFN-γ enhanced the interactions of ubiquitin-conjugating enzyme 9 (UBC9), small ubiquitin-like modifier (SUMO)-1 and SUMO-2/3 with LXR-α. Moreover, treatment with shRNA specific for them not only reduced LXR-α polyubiquitination but also reversed the IFN-γ-induced decrease in its expression. Two specific sumoylation sites in LXR-α, K22 and K326, were indispensable for its IFN-γ-induced polyubiquitination because the K22R and K326R mutations inhibited the polyubiquitination and degradation of LXR-α in IFN-γ-treated macrophages. In addition, K22R or K326R mutation almost completely restored ATP-binding cassette subfamily G member 1 (ABCG1)-mediated cholesterol efflux in IFN-γ-treated macrophages. Taken together, these findings indicate that IFN-γ promotes LXR-α degradation through a SUMO-ubiquitin-dependent pathway, which may inhibit cholesterol efflux mediated by ABCG1 from macrophages and promote the development of atherosclerosis.
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Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1/metabolismo , Colesterol/metabolismo , Interferón gamma/metabolismo , Receptores X del Hígado/metabolismo , Macrófagos/metabolismo , Animales , Células Cultivadas , Ratones , Células RAW 264.7RESUMEN
The offshore aquaculture environment is a potential water area with high concentrations of tiny plastics and feeding proteins. In this study, the negatively charged bovine serum albumin (BSA) and the positively charged lysozyme (LSZ) were used to explore the effects of protein corona on the aggregation, transport, and retention of polystyrene nanoplastics (NPs; 200, 500, and 1000 nm) in sea sand saturated with seawater of 35 practical salinity units (PSU). The BSA corona, which was formed by the adsorption of BSA on the surface of NPs, drove the dispersion of NPs (200 and 500 nm) due dominantly to the induced colloidal steric hindrance. For example, the aggregate sizes of 500 nm NP decreased from 1740 ± 87 nm to 765 ± 8 nm at 40 min, which resulted in the enhanced transportation of NP. The calculated interaction energies indicated the BSA corona-induced high energy barriers (>104 KBT) between 1000 nm NPs and sand surface, demonstrating the BSA-enhanced transport of 1000 nm NPs. The mass percentage recovered from the effluent (Meff) increased from 33.4% to 61.7%. Inversely, the LSZ corona triggered the aggregation of 200 nm NPs into the large aggregates via electrostatic adsorption and bridging effect, thereby inhibiting the transport of 200 nm NPs. Nevertheless, no LSZ corona was formed on the surface of 500 and 1000 nm NPs due to extremely low protein adsorption. Accordingly, LSZ cannot affect the stability and transport of these NPs. In the diluted seawater (3.5 PSU), the strong electrostatic attraction between positively charged LSZ and 500 nm NPs significantly increased and the LSZ corona formed, which induced the aggregation of 500 nm NPs. The Meff of NPs therefore decreased from 53.1% to 11.2%. Overall, the protein corona-mediated transport of NPs in seawater-saturated porous media depends on protein type, NP size, and seawater salinity.
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Nanopartículas , Corona de Proteínas , Microplásticos , Poliestirenos , Porosidad , Agua de MarRESUMEN
The association of the cation and anion of ionic liquids (ILs) dominates the absorbability of ILs by activated carbon (AC). Nevertheless, the mechanism behind the role of ion-pairs is largely unknown. In this study, the adsorption of a series of imidazolium derivative-based ILs by AC was involved in response to the octanol-water partition coefficient (KOW), hydrogen bonding acidity (α), ion-pair binding constants (KIP), binding energy of ion-pairs (Ebinding) and density functional theory (DFT) calculation of ILs. A significant positive correlation between lg KOW and Kd and between KIP and lg KOW was observed (p < 0.05). However, both Ebinding and α was inversely proportional to KIP. Hence, the substitution of oxygen-containing functional groups, such as carboxyethyl, 1-methoxyethyl, and 1-(ethoxycarbonyl)methyl, on imidazolium ring enhanced the hydrogen bond interaction with water molecules and then weakened the binding of imidazolium cation and [NTf2]-, thereby reducing the adsorption of ILs to AC. DFT calculation further revealed that the polar substitution improved the electron density and electronegativity of imidazolium skeleton. By contrast, the ILs functionalized with non-polar groups (e.g., butyl, allyl, and benzyl) generally displayed high KIP values and low α values. Consequently, the formation of hydrogen bond between the oxygen-containing functional groups of IL cation and water would facilitate the dissociation of IL ion-pairs and then decrease the adsorption of ILs on AC.
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In this study, the adsorption behaviors and mechanisms of Pb(II) and Zn(II) by animal-derived biochar (ADB) in single and binary metal systems were comparatively investigated. ADB contains considerable amounts of Ca/P components and is mainly composed of hydroxyapatite (HAP), which plays an important role in the adsorption of Pb(II) and Zn(II). The maximum adsorption capacities of Pb(II) and Zn(II) on ADB were in the order of Zn(II)-single (3.23 mmol g-1) > Pb(II)-single (2.74 mmol g-1) ≈ Pb(II)-binary (2.71 mmol g-1) > Zn(II)-binary (2.31 mmol g-1). In the single metal system, approximately 99.9% of the adsorbed Pb(II) existed as Pb5(PO4)3Cl, while the dominant adsorption mechanism of Zn(II) was cation exchange, followed by precipitation, accounting for 78.0%-80.6% and 19.4%-21.5% of the adsorption capacity, respectively. These findings were verified by X-ray diffraction refinement, X-ray photoelectron spectroscopy, metal speciation modeling, and Ca(II) exchange experiment. In the binary metal system, the proportion and form of Pb(II) precipitate remained unchanged. However, the binding of Zn(II) to ADB was completely dependent on the cation exchange with Ca(II), and no remarkable Zn(II) precipitation was observed. Phosphate released from HAP preferentially precipitated with Pb(II) than with Zn(II) when they coexisted. Consequently, Pb(II) competition may alter the Zn(II) adsorption mechanism on ADB. Nonetheless, ADB could serve as an efficient biochar for the simultaneous immobilization of Pb(II) and Zn(II) via different mechanisms.
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Carbón Orgánico , Adsorción , Animales , Plomo , ZincRESUMEN
Previous studies have shown that miR-210-3p is involved in the development and progression of atherosclerosis, but its specific mechanisms are still unclear. This study aims to reveal the mechanism of miR-210-3p and its target genes in macrophage lipid deposition and inflammatory response, and provide new ideas for the treatment of atherosclerosis. We found miR-210-3p increased sharply in the first 12 h induced by higher doses of ox-LDL in THP-1 macrophages and then gradually decreased. MiR-210-3p mimic transfection inhibited lipid uptake and inflammatory cytokine production in ox-LDL-induced macrophages. By inhibiting IGF2/IGF2R, miR-210-3p suppressed the expression of fatty acid transcriptase CD36 and transcription factor NF-κB in ox-LDL-induced macrophages. In conclusion, miR-210-3p inhibits the expression of CD36 and NF-κB by inhibiting IGF2 / IGF2R, thereby reducing lipid accumulation and inflammatory response in ox-LDL-induced macrophages. Enhancing miR-210-3p expression may be a new strategy for the treatment of atherosclerosis.
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Aterosclerosis/metabolismo , Inflamación/metabolismo , Factor II del Crecimiento Similar a la Insulina/antagonistas & inhibidores , Metabolismo de los Lípidos , MicroARNs/metabolismo , Animales , Apolipoproteínas E/genética , Humanos , Mediadores de Inflamación/metabolismo , Factor II del Crecimiento Similar a la Insulina/metabolismo , Lipoproteínas LDL/metabolismo , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Células THP-1RESUMEN
2D layered SnS2 is one of the most popular semiconductor photocatalysts. However, its performance on photocatalytic reduction of aromatic nitro compounds is unsatisfactory, due to charge carrier recombination and weak adsorption of active hydrogen from the hydrolysis of NaBH4. Herein, we have prepared CQDs @ Pd nanoclusters with Pd nanoparticles below 5â¯nm through an in-situ reducing Pd(â ¡) with CQDs containing some oxygen-containing groups at first. CQDs @ Pd-SnS2 is achieved through a strong interaction of sulfur ions bonding on nanometric Pd surface. The composite shows a stable and efficient visible-light-driven catalytic reduction of aromatic nitro compounds in H2O and NaBH4. Under 40â¯min visible light irradiation, the conversion rate of 4-NP attains 99.7% on CQDs @ Pd-SnS2. The first order reaction rate constant is 0.0332â¯min-1, 586.5, 202.4 and 31.9 times that on SnS2, CQDs-SnS2 and Pd-SnS2 in the condition of 20â¯mg·L-1 4-NP and excess NaBH4, respectively. The significant enhancement is ascribed to CQDs @ Pd promoting the charge carrier separation on SnS2 and increasing the adsorption of active hydrogen from the hydrolysis of NaBH4.
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The adsorption of 1-alkyl-3-methylimidazolium-type ionic liquids (ITILs) coupled with different counteranions (Tf2N-, PF6-, BF4-, and Cl-) with variational cation alkyl chain lengths (nâ¯=â¯2, 4, 6, and 8) to montmorillonite was investigated to explore the structural effect of ITILs on their adsorption. A series of montmorillonite with different cation exchange capacities (CECs) and possessing a set of homoionic K- and Cs-exchanged interlayer cations were also examined to assess the influence of montmorillonite structure and characteristics. The adsorption of ITILs to Na-saturated montmorillonite (Na-MAz) was counteranion-independent but increased with the increase in the alkyl chain length of the imidazolium cation. X-ray diffraction results indicated that ITIL cations with different alkyl chains lay flat between the montmorillonite interlayers with different contact angles. The uptake of ITILs by Na-MAz increased with the increase in the solution pH and decrease in ionic strength. Na-MAz exhibited greater adsorption than K- and Cs-saturated MAz due to the larger hydrated radii of Na+ than those of K+ and Cs+. The uptake of ITILs to Na-MZj (CECâ¯=â¯64â¯mmol/100â¯g) was almost half compared with that of Na-MAz (CECâ¯=â¯117â¯mmol/100â¯g). Consequently, this work demonstrated that the ITIL adsorption to montmorillonite was dependent on the structures of both adsorbate and adsorbent.
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BACKGROUND: Acute myocardial infarction (AMI) is followed by an acute inflammation involving inflammasome activation, thereby inducing cardiac dysfunction. Interleukin-17A (IL-17A) involves in many inflammatory diseases, but its roles in inflammation following AMI are still obscure. The aim of this study is to investigate the roles of IL-17A in the inflammatory response following AMI and its underlying mechanisms. METHODS AND RESULTS: NLRP3 inflammasome and AMPKα/p38MAPK/ERK1/2 signaling pathway were significantly activated under the induction of IL-17A in mouse peritoneal macrophages, which could be inhibited by AMPK inhibitor compound C (CC). Both p38MAPK and ERK1/2 inhibitors could partially inhibit the activation of NLRP3 inflammasome in macrophages treated by IL-17A. In vivo, IL-17A knockout not only decreased the infiltration of macrophages and the activation of NLRP3 inflammasome and AMPKα/p38MAPK/ERK1/2 signaling pathway in ischemic myocardium, but also improved cardiac function and reduced infarction size after the ligation of descending segment from left coronary artery for 3 days in mice, while IL-17A administration further aggravated the myocardial ischemic injury, which were prevented by CC administration. CONCLUSION: IL-17A aggravates inflammatory response during AMI by inducing macrophages infiltration and activating NLRP3 inflammasome through AMPKα/p38MAPK/ERK1/2 pathway.
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Proteínas Quinasas Activadas por AMP/inmunología , Inflamasomas/inmunología , Interleucina-17/inmunología , Sistema de Señalización de MAP Quinasas/inmunología , Macrófagos Peritoneales/inmunología , Proteína Quinasa 1 Activada por Mitógenos/inmunología , Proteína Quinasa 3 Activada por Mitógenos/inmunología , Isquemia Miocárdica/inmunología , Proteína con Dominio Pirina 3 de la Familia NLR/inmunología , Proteínas Quinasas p38 Activadas por Mitógenos/inmunología , Proteínas Quinasas Activadas por AMP/genética , Animales , Inflamasomas/genética , Interleucina-17/genética , Sistema de Señalización de MAP Quinasas/genética , Macrófagos Peritoneales/patología , Ratones , Ratones Noqueados , Proteína Quinasa 1 Activada por Mitógenos/genética , Proteína Quinasa 3 Activada por Mitógenos/genética , Isquemia Miocárdica/genética , Isquemia Miocárdica/patología , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteínas Quinasas p38 Activadas por Mitógenos/genéticaRESUMEN
The intersection of microfluidics and aptamer technologies holds particular promise for rapid progress in a plethora of applications across biomedical science and other areas. Here, the influence of microfluidics on the field of aptamers, from traditional capillary electrophoresis approaches through innovative modern-day approaches using micromagnetic beads and emulsion droplets, is reviewed. Miniaturizing aptamer-based bioassays through microfluidics has the potential to transform diagnostics and embedded biosensing in the coming years.
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Aptámeros de Nucleótidos/química , Bioensayo , Evolución Molecular Dirigida , Técnicas Analíticas MicrofluídicasRESUMEN
INTRODUCTION: Both Global Registry of Acute Coronary Events (GRACE) risk score and CYP2C19 metabolizer status can independently predict major adverse cardiac events (MACEs) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). We investigated whether their combination could better predict MACE occurrence in patients with ACS undergoing PCI. MATERIALS AND METHODS: This retrospective cohort study included 548 consecutive patients with ACS undergoing PCI. A cumulative MACE curve was calculated using the Kaplan-Meier method. Multivariate Cox regression was used to identify MACE predictors. The predictive value of GRACE risk score alone and CYP2C19 metabolizer status was estimated by the area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: In a median of 28.58â¯months, 17 patients (3%) were lost to follow-up, and 62 (11.3%) experienced MACEs. Multivariate Cox regression analysis showed that both GRACE score and CYP2C19 metabolizer status were independent MACE predictors (hazard ratio 1.019, 95% CI 1.011-1.027, pâ¯<â¯0.001; hazard ratio 2.383, 95% CI 1.601-3.547, pâ¯<â¯0.001, respectively). Kaplan-Meier analysis showed that CYP2C19 PM increased the MACE risk (log rank testâ¯=â¯10.848, pâ¯=â¯0.004). The GRACE score adjustment by CYP2C19 metabolizer status enhanced the predictive value (AUC increased from 0.682 for GRACE score alone to 0.731 for GRACE score plus CYP2C19 metabolizer). This result was further verified by IDI and NRI. CONCLUSIONS: CYP2C19 metabolizer status and GRACE score are readily available predictive approaches for MACEs, and their combination derives a more accurate long-term MACE prediction in clopidogrel-treated patients with ACS undergoing PCI.
Asunto(s)
Síndrome Coronario Agudo/genética , Citocromo P-450 CYP2C19/genética , Intervención Coronaria Percutánea/métodos , Síndrome Coronario Agudo/patología , Anciano , Estudios de Cohortes , Citocromo P-450 CYP2C19/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Factores de RiesgoRESUMEN
Sanguisorba officinalis (the Chinese name is DiYu, DY) exerts significant anti-proliferative activities against colorectal cancer (CRC) cells. Since most of CRC result from the aberrant activation of the Wnt/ß-catenin signaling pathway, inhibitors of the Wnt pathway are considered as promising anti-CRC agents. This study aimed to investigate whether DY could be a potential herbal Wnt inhibitor, and the bioactive constituents and underlying molecular mechanisms for DY's inhibiting activities would be studied as well. Accordingly, the inhibitory activities of DY and its main components against the Wnt pathway were assessed using the single-luciferase reporter assay based on HEK293 cells. Additionally, the levels of key Wnt-related genes or proteins were measured to verify the inhibitory effects on the Wnt pathway of CRC cells. Finally, the underlying mechanisms accounting for the efficacy of candidate drugs were explored by the transcriptomic study. Results show that DY and its tannins (RZ), and saponins (ZG) significantly inhibited the Wnt pathway of HEK293 cells activated by wnt3a. However, their respective constituents were not effective as expected. Additionally, DY and RZ prominently down-regulated the levels of ß-catenin and Wnt-targeted genes including Axin2, c-Myc or CyclinD1 of three CRC cells. Transcriptomic profiling study suggests that the down-regulation of the mRNA levels of Wnt-related genes such as LPAR6 may be associated with the inhibitory effects of DY and RZ on the Wnt pathway of HT29 cells. Therefore, our studies first uncovered the blocking activity of DY on the Wnt pathway, providing evidence for the rationale of developing Wnt inhibitors from DY as anti-CRC agents.