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[This corrects the article DOI: 10.1371/journal.pone.0232042.].
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Based on the processing and compatibility, this study explored the effects of components in Corni Fructus(CF) and Astragali Radix(AR) on plasma metabolomics in diabetic nephropathy rats. SD rats were randomly divided into four groups and diabetic nephropathy rat model was induced by high-fat diet combined with 30 mg·kg~(-1) streptozotocin(STZ). Histopathological observations of kidney tissue sections of rats in each group were conducted using HE, PAS, and Masson staining. Ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) metabolomics method was employed to investigate the effects of CF before and after wine-processing combined with AR-related components on plasma metabolites in diabetic nephropathy rats. After drug treatment, kidney tissue damage and interstitial collagen fiber deposition area in diabetic nephropathy rats were improved to varying degrees(P<0.001). The detection results of plasma metabolomics showed that 71 biomarkers related to the pathogenesis of diabetic nephropathy were identified in diseased rats, mainly involving linoleic acid metabolism, caffeine metabolism, glycerophospholipid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arachidonic acid metabolism, phenylalanine metabolism, retinol metabolism, and ether lipid metabolism. After drug intervention, 26 of them were significantly downregulated, with better efficacy observed in precision processed herb-pair group(P-CG_5). This study elucidated from the perspective of plasma metabolomics that P-CG_5 could improve metabolic disorders in diabetic nephropathy through pathways such as phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and caffeine metabolism, providing theoretical support and experimental basis for the clinical application of CF and AR compatibility in traditional Chinese medicine.
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Cornus , Nefropatías Diabéticas , Medicamentos Herbarios Chinos , Metabolómica , Ratas Sprague-Dawley , Espectrometría de Masas en Tándem , Animales , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/metabolismo , Ratas , Masculino , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Cornus/química , Astragalus propinquus/química , Vino/análisis , Humanos , Riñón/efectos de los fármacos , Riñón/metabolismoRESUMEN
OBJECTIVE: To investigate the anti-tumor effects of cinobufacini (CINO) on hepatocellular carcinoma (HCC) induced by des-gamma-carboxy-prothrombin (DCP) and to uncover the underlying mechanisms. METHODS: The inhibitory effect of CINO on HCC cell proliferation was evaluated using the cell counting kit-8 method, and the apoptosis rate was quantified using flow cytometry. Immunofluorescence and Western blot analyses were used to investigate the differential expression of proteins associated with cell growth, apoptosis, migration, and invasion pathways after CINO treatment. The therapeutic potential of CINO for HCC was confirmed, and the possibility of combining cinobufacini with c-Met inhibitor for the treatment of primary HCC was further validated by in vivo experiments. RESULTS: Under the induction of DCP, CINO inhibited the activity of HCC cells, induced apoptosis, and inhibited migration and invasion. Upon the induction of DCP, CINO regulated c-Met activation and the activation of the phosphatidylinositol-3 kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) pathways. In a mouse model of HCC, CINO exhibited significant antitumor effects by inhibiting the phosphorylation of c-Met and the downstream PI3K/AKT and MEK/ERK pathways in tumor tissues. CONCLUSIONS: CINO inhibited HCC cell growth, promoted apoptosis, and suppressed HCC cell invasion and migration by targeting c-Met and PI3K/AKT and MEK/ERK signaling pathways under DCP induction.
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Tumor microenvironment (TME)-responsive chemodynamic therapy (CDT) is severely hindered by insufficient intracellular H2O2 level that seriously deteriorates antitumor efficacy, albeit with its extensively experimental and theoretical research. Herein, we designed atomically dispersed FeCo dual active sites anchored in porous carbon polyhedra (termed FeCo/PCP), followed by loading with glucose oxidase (GOx) and anticancer doxorubicin (DOX), named FeCo/PCP-GOx-DOX, which converted glucose into toxic hydroxyl radicals. The loaded GOx can either decompose glucose to self-supply H2O2 or provide fewer nutrients to feed the tumor cells. The as-prepared nanozyme exhibited the enhanced in vitro cytotoxicity at high glucose by contrast with those at less or even free of glucose, suggesting sufficient accumulation of H2O2 and continual transformation to OH for CDT. Besides, the FeCo/PCP-GOx-DOX can subtly integrate starvation therapy, the FeCo/PCP-initiated CDT, and DOX-inducible chemotherapy (CT), greatly enhancing the therapeutic efficacy than each monotherapy.
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Doxorrubicina , Glucosa Oxidasa , Peróxido de Hidrógeno , Peróxido de Hidrógeno/metabolismo , Peróxido de Hidrógeno/química , Doxorrubicina/farmacología , Doxorrubicina/química , Doxorrubicina/uso terapéutico , Glucosa Oxidasa/metabolismo , Glucosa Oxidasa/química , Humanos , Animales , Microambiente Tumoral/efectos de los fármacos , Ratones , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Neoplasias/tratamiento farmacológico , Glucosa/metabolismo , Dominio CatalíticoRESUMEN
Deoxynivalenol (DON), a mycotoxin produced by Fusarium, poses a significant risk to human health and the environment. Therefore, the development of a highly sensitive and accurate detection method is essential to monitor the pollution situation. In response to this imperative, we have devised an advanced split-type photoelectrochemical (PEC) sensor for DON analysis, which leverages self-shedding MOF-nanocarriers to modulate the photoelectric response ability of PEC substrate. The PEC sensing interface was constructed using CdS/MoSe2 heterostructures, while the self-shedding copper peroxide nanodots@ZIF-8 (CPNs@ZIF-8) served as the Cu2+ source for the in-situ ion exchange reaction, which generated a target-related signal reduction. The constructed PEC sensor exhibited a broad linear range of 0.1 pg mL-1 to 500 ng mL-1 with a low detection limit of 0.038 pg mL-1, demonstrating high stability, selectivity, and proactivity. This work not only introduces innovative ideas for the design of photosensitive materials, but also presents novel sensing strategies for detecting various environmental pollutants.
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Compuestos de Cadmio , Técnicas Electroquímicas , Estructuras Metalorgánicas , Tricotecenos , Tricotecenos/análisis , Tricotecenos/química , Técnicas Electroquímicas/métodos , Compuestos de Cadmio/química , Estructuras Metalorgánicas/química , Sulfuros/química , Límite de Detección , Procesos Fotoquímicos , Intercambio IónicoRESUMEN
Bruton's tyrosine kinase (BTK) has emerged as a therapeutic target for B-cell malignancies, which is substantiated by the efficacy of various irreversible or reversible BTK inhibitors. However, on-target BTK mutations facilitating evasion from BTK inhibition lead to resistance that limits the therapeutic efficacy of BTK inhibitors. In this study we employed structure-based drug design strategies based on established BTK inhibitors and yielded a series of BTK targeting compounds. Among them, compound S-016 bearing a unique tricyclic structure exhibited potent BTK kinase inhibitory activity with an IC50 value of 0.5 nM, comparable to a commercially available BTK inhibitor ibrutinib (IC50 = 0.4 nM). S-016, as a novel irreversible BTK inhibitor, displayed superior kinase selectivity compared to ibrutinib and significant therapeutic effects against B-cell lymphoma both in vitro and in vivo. Furthermore, we generated BTK inhibitor-resistant lymphoma cells harboring BTK C481F or A428D to explore strategies for overcoming resistance. Co-culture of these DLBCL cells with M0 macrophages led to the polarization of M0 macrophages toward the M2 phenotype, a process known to support tumor progression. Intriguingly, we demonstrated that SYHA1813, a compound targeting both VEGFR and CSF1R, effectively reshaped the tumor microenvironment (TME) and significantly overcame the acquired resistance to BTK inhibitors in both BTK-mutated and wild-type BTK DLBCL models by inhibiting angiogenesis and modulating macrophage polarization. Overall, this study not only promotes the development of new BTK inhibitors but also offers innovative treatment strategies for B-cell lymphomas, including those with BTK mutations.
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Agammaglobulinemia Tirosina Quinasa , Antineoplásicos , Resistencia a Antineoplásicos , Inhibidores de Proteínas Quinasas , Animales , Humanos , Ratones , Agammaglobulinemia Tirosina Quinasa/antagonistas & inhibidores , Agammaglobulinemia Tirosina Quinasa/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Descubrimiento de Drogas , Resistencia a Antineoplásicos/efectos de los fármacos , Piperidinas/farmacología , Piperidinas/uso terapéutico , Piperidinas/química , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/química , Relación Estructura-Actividad , Receptores de Factores de Crecimiento Endotelial Vascular/química , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Nowadays, signal enhancement is imperative to increase sensitivity of advanced ECL devices for expediting their promising applications in clinic. In this work, photodynamic-assisted electrochemiluminescence (PDECL) device was constructed for precision diagnosis of Parkinson, where an advanced emitter was prepared by electrostatically linking 2,6-dimethyl-8-(3-carboxyphenyl)4,4'-difluoroboradiazene (BET) with 1-butyl-3-methylimidazole tetrafluoroborate ([BMIm][BF4]). Specifically, protoporphyrin IX (PPIX) can trigger the photodynamic reaction under light irradiation with a wavelength of 450 nm to generate lots of singlet oxygen (1O2), showing a 2.43-fold magnification in the ECL responses. Then, the aptamer (Apt) was assembled on the functional BET-[BMIm] for constructing a "signal off" ECL biosensor. Later on, the PPIX was embedded into the G-quadruplex (G4) of the Apt to magnify the ECL signals for bioanalysis of α-synuclein (α-syn) under light excitation. In the optimized surroundings, the resulting PDECL sensor has a broad linear range of 100.0 aM â¼ 10.0 fM and a low limit of detection (LOD) of 63 aM, coupled by differentiating Parkinson patients from normal individuals according to the receiver operating characteristic (ROC) curve analysis of actual blood samples. Such research holds great promise for synthesis of other advanced luminophores, combined with achieving an early clinical diagnosis.
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Compuestos de Boro , Técnicas Electroquímicas , Mediciones Luminiscentes , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/sangre , Compuestos de Boro/química , Técnicas Biosensibles/métodos , alfa-Sinucleína/análisis , alfa-Sinucleína/sangre , Protoporfirinas/química , Aptámeros de Nucleótidos/química , Límite de DetecciónRESUMEN
Alternative energy sources are required due to the decline in fossil fuel resources. Therefore, devices that utilize hydrovoltaic technology and light energy have drawn widespread attention because they are emission-free and solar energy is inexhaustible. However, previous investigations mainly focused on accelerating the water evaporation rate at the electrode interface. Here, a cooperative photoelectrochemical effect on a hydrovoltaic chip is achieved using NH2-MIL-125-modified TiO2 nanotube arrays (NTs). This device demonstrated significantly improved evaporation-triggered electricity generation. Under LED illumination, the open-circuit voltage (VOC) of the NH2-MIL-125/TiO2NTs active layer of the hydrovoltaic chip was enhanced by 90.3% (up to 400.2 mV). Furthermore, the prepared hydrovoltaic chip showed good high-salinity tolerance, maintaining 74.6% of its performance even in 5 M NaCl. By introducing a Schiff-based reaction between the active layer and formaldehyde, a fully integrated flexible sensor was successfully fabricated for formaldehyde monitoring, and a low limit of detection of 5.2 × 10-9 M was achieved. This novel strategy for improving the performance of hydrovoltaic devices offers a completely new general approach to construct self-powered devices for point-of-care sensing.
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Técnicas Electroquímicas , Formaldehído , Titanio , Formaldehído/análisis , Formaldehído/química , Titanio/química , Técnicas Electroquímicas/métodos , Técnicas Electroquímicas/instrumentación , Nanotubos/química , Salinidad , Procesos Fotoquímicos , Electrodos , Límite de DetecciónRESUMEN
Food allergy (FA) poses a growing global food safety concern, yet no effective cure exists in clinics. Previously, we discovered a potent antifood allergy compound, butyrolactone I (BTL-I, 1), from the deep sea. Unfortunately, it has a very low exposure and poor pharmacokinetic (PK) profile in rats. Therefore, a series of structural optimizations toward the metabolic pathways of BTL-I were conducted to provide 18 derives (2-19). Among them, BTL-MK (19) showed superior antiallergic activity and favorable pharmacokinetics compared to BTL-I, being twice as potent with a clearance (CL) rate of only 0.5% that of BTL-I. By oral administration, Cmax and area under the concentration-time curve (AUC0-∞) were 565 and 204 times higher than those of BTL-I, respectively. These findings suggest that butyrolactone methyl ketone (BTL-BK) could serve as a drug candidate for the treatment of FAs and offer valuable insights into optimizing the druggability of lead compounds.
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4-Butirolactona , Antialérgicos , Animales , 4-Butirolactona/análogos & derivados , 4-Butirolactona/farmacología , 4-Butirolactona/química , 4-Butirolactona/farmacocinética , 4-Butirolactona/administración & dosificación , Administración Oral , Ratas , Humanos , Antialérgicos/farmacocinética , Antialérgicos/farmacología , Antialérgicos/química , Antialérgicos/administración & dosificación , Relación Estructura-Actividad , Masculino , Ratas Sprague-Dawley , Disponibilidad Biológica , Hipersensibilidad a los Alimentos/tratamiento farmacológico , RatonesRESUMEN
Exploring efficient photoactive material presents an intriguing opportunity to enhance the analytical performance of photoelectrochemical (PEC) sensor in the environmental analysis. In this work, a sandwich-structured multi-interface Co9S8@ZnIn2S4/CdSe QDs dual Z-Scheme heterojunction, derived from metal-organic framework (MOF), was synthesized as a sensing platform for chlorpyrifos detection, by integrating with enzyme-induced in situ insoluble precipitates strategy. The meticulously designed Co9S8@ZnIn2S4/CdSe QDs exhibited enhanced charge separation efficiency and was proved to be a highly effective sensing platform for the immobilization of biomolecules, attributing to the intrinsic dual Z-Scheme heterojunction and the distinctive hollow structure. The proposed PEC sensing platform combined with enzyme-induced in situ precipitate signal amplification strategy achieved superior performance for sensing of chlorpyrifos (CPF), showing in wide linear range (1.0 pg mL-1-100 ng mL-1), with a limit of detection (0.6 pg mL-1), excellent selectivity, and stability. This work offers valuable insights for the design of novel advanced photoactive materials aimed at detecting environmental pollutants with low level concentration.
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Técnicas Biosensibles , Cloropirifos , Técnicas Electroquímicas , Límite de Detección , Estructuras Metalorgánicas , Puntos Cuánticos , Cloropirifos/análisis , Estructuras Metalorgánicas/química , Técnicas Electroquímicas/métodos , Puntos Cuánticos/química , Compuestos de Cadmio/química , Compuestos de Selenio/química , Cobalto/química , Insecticidas/análisisRESUMEN
The development of sensitive, selective, and rapid methods to detect bacteria in complex media is essential to ensuring human health. Virulence factors, particularly pore-forming toxins (PFTs) secreted by pathogenic bacteria, play a crucial role in bacterial diseases and serve as indicators of disease severity. In this study, a nanochannel-based label-free electrochemical sensing platform was developed for the detection of specific pathogenic bacteria based on their secreted PFTs. In this design, wood substrate channels were functionalized with a Fe-based metal-organic framework (FeMOF) and then protected with a layer of phosphatidylcholine (PC)-based phospholipid membrane (PM) that serves as a peroxidase mimetic and a channel gatekeeper, respectively. Using Staphylococcus aureus (S. aureus) as the model bacteria, the PC-specific PFTs secreted by S. aureus perforate the PM layer. Now exposed to the FeMOF, uncharged 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) molecules in the electrolyte undergo oxidation to cationic products (ABTSâ¢+). The measured transmembrane ionic current indicates the presence of S. aureus and methicillin-resistant S. aureus (MRSA) with a low detection limit of 3 cfu mL-1. Besides excellent specificity, this sensing approach exhibits satisfactory performance for the detection of target bacteria in the complex media of food.
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Toxinas Bacterianas , Técnicas Biosensibles , Técnicas Electroquímicas , Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/análisis , Estructuras Metalorgánicas/química , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Peroxidasa/metabolismo , Peroxidasa/química , Staphylococcus aureus/aislamiento & purificación , Staphylococcus aureus/metabolismoRESUMEN
As an important prognostic indicator in breast cancer, human epithelial growth factor receptor-2 (HER-2) is of importance for assessing prognosis of breast cancer patients, whose accurate and facile analysis are imperative in clinical diagnosis and treatment. Herein, photoactive Z-scheme UiO-66/CdIn2S4 heterojunction was constructed by a hydrothermal method, whose optical property and photoactivity were critically investigated by a range of techniques, combined by elucidating the interfacial charge transfer mechanism. Meanwhile, PtPdCu nanoflowers (NFs) were fabricated by a simple aqueous wet-chemical method, whose peroxidase (POD)-mimicking catalytic activity was scrutinized by representative tetramethylbenzidine (TMB) oxidation in H2O2 system. Taken together, the UiO-66/CdIn2S4 based photoelectrochemical (PEC) aptasensor was established for quantitative analysis of HER-2, where the detection signals were further magnified through catalytic precipitation reaction towards 4-chloro-1-naphthol (4-CN) oxidation (assisted by the PtPdCu NFs nanozyme). The PEC aptasensor presented a broader linear range within 0.1 pg mL-1-0.1 µg mL-1 and a lower limit of detection of 0.07 pg mL-1. This work developed a new PEC aptasensor for ultrasensitive determination of HER-2, holding substantial promise for clinical diagnostics.
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Aptámeros de Nucleótidos , Técnicas Biosensibles , Cobre , Técnicas Electroquímicas , Platino (Metal) , Receptor ErbB-2 , Receptor ErbB-2/análisis , Humanos , Técnicas Electroquímicas/métodos , Cobre/química , Platino (Metal)/química , Técnicas Biosensibles/métodos , Aptámeros de Nucleótidos/química , Límite de Detección , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/análisis , Estructuras Metalorgánicas/química , Nanoestructuras/química , Níquel/química , Bencidinas/química , Procesos Fotoquímicos , CatálisisRESUMEN
Reactive oxygen species (ROS)-centered chemodynamic therapy (CDT) holds significant potential for tumor-specific treatment. However, insufficient endogenous H2O2 and extra glutathione within tumor microenvironment (TME) severely deteriorate the CDT's effectiveness. Herein, rich-Zn-Co3O4/N-doped porous carbon (Zn-Co3O4/NC) was fabricated by two-step pyrolysis, and applied to build high-efficiency nano-platform for synergistic cancer therapy upon combination with glucose oxidase (GOx), labeled Zn-Co3O4/NC-GOx for clarity. Specifically, the multiple enzyme-like activities of the Zn-Co3O4/NC were scrutinously investigated, including peroxidase-like activity to convert H2O2 to O2â-, catalase-like activity to decompose H2O2 into O2, and oxidase-like activity to transform O2 to O2â-, which achieved the CDT through the catalytic cascade reaction. Simultaneously, GOx reacted with intracellular glucose to produce gluconic acid and H2O2, realizing starvation therapy. In the acidic TME, the Zn-Co3O4/NC-GOx rapidly caused intracellular Zn2+ pool overload and disrupted cellular homeostasis for ion-intervention therapy. Additionally, the Zn-Co3O4/NC exhibited glutathione peroxidase-like activity, which consumed glutathione in tumor cells and reduced the ROS consumption for ferroptosis. The tumor treatments offer some constructive insights into the nanozyme-mediated catalytic medicine, coupled by avoiding the TME limitations.
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Cobalto , Peróxido de Hidrógeno , Neoplasias , Óxidos , Humanos , Porosidad , Especies Reactivas de Oxígeno , Glucosa Oxidasa , Imidazoles , Carbono , Glutatión , Zinc , Neoplasias/tratamiento farmacológico , Línea Celular Tumoral , Microambiente TumoralRESUMEN
Metal nanoparticles could be accumulated in soils, which threatens the ecological stability of crops. Investigating the effects of cuprous oxide nanoparticles (Cu2O-NPs) on photosystem â ¡ (PSâ ¡) of wheat seedling leaves holds considerable importance in comprehending the implications of Cu2O-NPs on crop photosynthesis. Following the hydroponic method, we investigated the effects of 0, 10, 50, 100, and 200 mg·L-1 Cu2O-NPs on chlorophyll fluorescence induction kinetics and photosynthetic-related genes in wheat seedlings of "Zhoumai 18". The results showed that, with the increases of Cu2O-NPs concentrations, chlorophyll contents in wheat leaves decreased, and the standardization of the OJIP curve showed a clearly K-phase (ΔKï¼0). Cu2O-NPs stress increased the parameters of active PSâ ¡ reaction centers, including the absorption flux per active RC (ABS/RC), the trapping flux per active RC (TRo/RC), the electron transport flux per active RC (ETo/RC), and the dissipation flux per active RC (DIo/RC). Cu2O-NPs stress decreased the parameters of PSâ ¡ energy distribution ratio including the maximum quantum yield of PSâ ¡ (φPo), the quantum yield of electron transport from QA (φEo), and the probability that a trapped exciton moved an electron further than QA (Ψo), while increased the quantum ratio for heat dissipation (φDo). Moreover, there was a decrease in photosynthetic quantum yield Y(â ¡), photochemical quenching coefficient (qP), net photosynthetic rate (Pn), stomatal conductance (gs), intercellular CO2 concentration (Ci), and transpiration rate (Tr) of leaves with the increases of Cu2O-NPs concentration. Under Cu2O-NPs stress, the expression levels of genes which included PSâ ¡ genes (PsbD, PsbP, Lhcb1), Rubisco large subunit genes (RbcL), cytochrome b6/f complex genes (PetD, Rieske), and ATP synthase genes (AtpA, AtpB, AtpE, AtpI) were downregulated. These results indicated that Cu2O-NPs stress altered the activity and structure of PSâ ¡ in wheat seedlings, affected the activity of PSâ ¡ reaction centers, performance parameters of PSâ ¡ donor and acceptor sides. PSâ ¡ related genes were downregulated and exhibited significant concentration effects.
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Clorofila , Cobre , Nanopartículas del Metal , Fotosíntesis , Complejo de Proteína del Fotosistema II , Plantones , Triticum , Triticum/metabolismo , Triticum/genética , Cobre/toxicidad , Clorofila/metabolismo , Plantones/metabolismo , Plantones/efectos de los fármacos , Complejo de Proteína del Fotosistema II/metabolismo , Fotosíntesis/efectos de los fármacos , Fluorescencia , Nanopartículas del Metal/química , Nanopartículas del Metal/toxicidad , Contaminantes del Suelo/metabolismo , Contaminantes del Suelo/toxicidad , Hojas de la Planta/metabolismo , Hojas de la Planta/efectos de los fármacos , CinéticaRESUMEN
Chronic wounds of significant severity and acute injuries are highly vulnerable to fungal infections, drastically impeding the expected wound healing trajectory. The clinical use of antifungal therapeutic drug is hampered by poor solubility, high toxicity and adverse reactions, thereby necessitating the urgent development of novel antifungal therapy strategy. Herein, this study proposes a new strategy to enhance the bioactivity of small-molecule antifungal drugs based on multifunctional metal nanozyme engineering, using amphotericin B (AmB) as an example. AmB-decorated gold nanoparticles (AmB@AuNPs) are synthesized by a facile one-pot reaction strategy, and the AmB@AuNPs exhibit superior peroxidase (POD)-like enzyme activity, with maximal reaction rates (Vmax) 3.4 times higher than that of AuNPs for the catalytic reaction of H2O2. Importantly, the enzyme-like activity of AuNPs significantly enhanced the antifungal properties of AmB, and the minimum inhibitory concentrations of AmB@AuNPs against Candida albicans (C. albicans) and Saccharomyces cerevisiae (S. cerevisiae) W303 are reduced by 1.6-fold and 50-fold, respectively, as compared with AmB alone. Concurrent in vivo studies conducted on fungal-infected wounds in mice underscored the fundamentally superior antifungal ability and biosafety of AmB@AuNPs. The proposed strategy of engineering antifungal drugs with nanozymes has great potential for enhanced therapy of fungal infections and related diseases.
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Anfotericina B , Antifúngicos , Candida albicans , Oro , Nanopartículas del Metal , Pruebas de Sensibilidad Microbiana , Oro/química , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/uso terapéutico , Anfotericina B/farmacología , Anfotericina B/química , Anfotericina B/uso terapéutico , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Candida albicans/efectos de los fármacos , Animales , Saccharomyces cerevisiae/efectos de los fármacos , RatonesRESUMEN
Oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are essential for the development of excellent bifunctional electrocatalysts, which are key functions in clean energy production. The emphasis of this study lies in the rapid design and investigation of 153 MN4-graphene (Gra)/ MXene (M2NO) electrocatalysts for ORR/OER catalytic activity using machine learning (ML) and density functional theory (DFT). The DFT results indicated that CoN4-Gra/Ti2NO had both good ORR (0.37 V) and OER (0.30 V) overpotentials, while TiN4-Gra/M2NO and MN4-Gra/Cr2NO had high overpotentials. Our research further indicated orbital spin polarization and d-band centers far from the Fermi energy level, affecting the adsorption energy of oxygen-containing intermediates and thus reducing the catalytic activity. The ML results showed that the gradient boosting regression (GBR) model successfully predicted the overpotentials of the monofunctional catalysts RhN4-Gra/Ti2NO (ORR, 0.39 V) and RuN4-Gra/W2NO (OER, 0.45 V) as well as the overpotentials of the bifunctional catalyst RuN4-Gra/W2NO (ORR, 0.39 V; OER, 0.45 V). The symbolic regression (SR) algorithm was used to construct the overpotential descriptors without environmental variable features to accelerate the catalyst screening and shorten the trial-and-error costs from the source, providing a reliable theoretical basis for the experimental synthesis of MXene heterostructures.
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Based on the typical city survey data and statistics of Guangdong Provinceï¼ a 2018-based 3 km×3 km gridded greenhouse gas emissions inventory was developed for Guangdong Province using the combination of top-down and bottom-up emission factor methods. The inventory covered the CO2ï¼ CH4ï¼ and N2O emissions from energyï¼ industrial processesï¼ agricultureï¼ land use change and forestï¼ waste managementï¼ and indirect sources. The results showed that estimates for CO2ï¼ CH4ï¼ and N2O in Guangdong Province for the year 2018 were 8.5×108ï¼ 1.9×106ï¼ and 1.1×105 tï¼ respectivelyï¼ and 8.5×108ï¼ 4.0×107ï¼ and 3.4×107 t by equivalent carbon dioxideï¼ totaling 9.2×108 t. CO2 was the main greenhouse gas in Guangdong Provinceï¼ accounting for 92.0% of the total emissions. Energy and indirect sources were the main emission sourcesï¼ accounting for 77.9% and 7.6%ï¼ respectivelyï¼ totaling 85.5%. Spatial distributions illustrated that most grids were greenhouse gas emissionsï¼ whereas some others were greenhouse gas sinksï¼ the greenhouse gas emissions were distributed mainly in the Pearl River Delta region and had certain characteristics of distribution along the road network and channels. The greenhouse gas grids of high emission were mainly the locations of high energy-consuming enterprises such as large power plantsï¼ steel millsï¼ and cement plants.
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Bisphenol A (BPA), an important endocrine disrupting compound, has infiltrated human daily lives through electronic devices, food containers, and children's toys. Developing of novel BPA assay methods with high sensitivity holds tremendous importance in valuing the pollution state. Here, we constructed an ultrasensitive photoelectrochemical (PEC) aptasensor for BPA determination by regulating photoactivities of CdS/Ni-based metal-organic framework (CdS/Ni-MOF) with [Ru(bpy)2dppz]2+ sensitizer. CdS/Ni-MOF spheres exhibited excellent photocatalytic performance, serving as a potential sensing platform for the construction of target recognition process. [Ru(bpy)2dppz]2+ were embedded into DNA double-stranded structure, functioning as sensitizer for modulating the signal response of the developed PEC aptasensor. The proposed PEC sensor exhibited outstanding analytical performances, including a wide linear range (0.1 to 1000.0 nM), low detection limit (0.026 nM, at 3σ/m), excellent selectivity, and high stability. This work provides a perspective for the design of ideal photosensitive materials and signal amplification strategies and extends their application in environment analysis.
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Técnicas Biosensibles , Estructuras Metalorgánicas , Fenoles , Niño , Humanos , Sustancias Intercalantes , Técnicas Biosensibles/métodos , Compuestos de Bencidrilo , ADNRESUMEN
Osteoporosis is a systemic skeletal disease that seriously endangers the health of middle-aged and older adults. Recently, with the continuous deepening of research, an increasing number of studies have revealed gut microbiota as a potential target for osteoporosis, and the research concept of the gut-bone axis has gradually emerged. Additionally, the intake of dietary nutrients and the adoption of dietary patterns may affect the gut microbiota, and alterations in the gut microbiota might also influence the metabolic status of the host, thus adjusting bone metabolism. Based on the gut-bone axis, dietary intake can also participate in the modulation of bone metabolism by altering abundance, diversity, and composition of gut microbiota. Herein, combined with emerging literatures and relevant studies, this review is aimed to summarize the impacts of different dietary components and patterns on osteoporosis by acting on gut microbiota, as well as underlying mechanisms and proper dietary recommendations.
Asunto(s)
Microbioma Gastrointestinal , Osteoporosis , Persona de Mediana Edad , Humanos , Anciano , DietaRESUMEN
Adenosine triphosphate (ATP) universally exists in all living organisms and holds a paramount role as a fundamental energy molecule in daily life. The abnormal concentration of ATP is closely related to many diseases, making the highly efficient detection of ATP very urgent. In this study, a dual-mode sensing system was developed to detect ATP sensitively and selectively via both DPV and fluorescence (FL) techniques, based on the strong interaction of ATP and Zn (II) nodes of zeolitic imidazolate framework-90 (ZIF-90). The disassembly of ZIF-90 further induced the subsequent release of pre-loaded rhodamine B (RhB). Benefitting from the robust host-guest recognition of ß-cyclodextrin (ß-CD) towards RhB, an enzyme-free and highly specific DPV detection strategy was established with the linear detecting range of 10.0-1.0 × 108 pM and the limit of detection (LOD) as low as 0.13 pM. Meanwhile, the FL sensing mode based on RhB exhibits comparable sensing performance with the linearity range of 10.0-1.0 × 107 pM and the LOD of 0.29 pM. Furthermore, the enzyme-free ATP sensing system exhibit outstanding long-term storage stability. The two-mode sensing platform was successfully applied to detect the ATP in human serum samples with the yielded result highly agree with the results of commercial ELISA kits. This dual-mode sensing platform is inspiring and paves the road for developing high-performance biosensor, demonstrating enormous potential for vitro diagnosis and practice clinic.