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Although zeolitic imidazolate frameworks (ZIFs) possess the merits of orderly porosity, high permeability, and easy functionalization, the transformation of ZIFs into the real active species and the promotion of the catalytic efficiency and stability are still challenging. Herein, CoMo-based three-dimensional (3D) hollow nanocages composed of interconnected nanosheets are fabricated by in-situ etching metal-organic framework (ZIF-67) under the aid of MoO42-. X-ray photoelectron spectroscopy (XPS) and in-situ Raman confirm that Mo leaching can accelerate surface reconstruction and generate CoOOH active sites after continuous oxidation. Benefiting from the nanostructure and electronic properties after surface reconstruction, the engineered CoMo-30 exhibits the lowest overpotential of 280 mV at 30 mA cm-2 and robust stability over 110 h in 1 M KOH media for oxygen evolution reaction (OER), which significantly surpasses the other counterparts and commercial RuO2. Density functional theory (DFT) calculations indicate that CoMo-30 has a lower free energy of *O â *OOH as rate determining step (RDS), suggesting that CoOOH sites play a crucial role in enhancing the activity and kinetics of OER. This work provides valuable insights into the rational design of hollow structures and the structure-composition-activity relationship during the electrochemical reaction process.
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Direct Methanol Fuel Cell (DMFC) is a powerful system for generating electrical energy for various applications. However, there are several limitations that hinder the commercialization of DMFCs, such as the expense of platinum (Pt) at market price, sluggish methanol oxidation reaction (MOR) due to carbon monoxide (CO) formation, and slow electrooxidation kinetics. This work introduces carbon nanocages (CNCs) that were obtained through the pyrolysis of polypyrrole (Ppy) as the carbon source. The CNCs were characterized using BET, XRD, HRTEM, TEM, SEM, and FTIR techniques. The CNCs derived from the Ppy source, pyrolyzed at 750 °C, exhibited the best morphologies with a high specific surface area of 416 m2g-1, allowing for good metal dispersion. Subsequently, PtRu catalyst was doped onto the CNC-Ppy750 support using chemical reduction and microwave-assisted methods. In electrochemical tests, the PtRu/CNC-Ppy750 electrocatalyst demonstrated improved CO tolerance and higher performance in MOR compared to PtRu-supported commercial carbon black (CB), with values of 427 mA mg-1 and 248 mA mg-1, respectively. The superior MOR performance of PtRu/CNC-Ppy750 was attributed to its high surface area of CNC support, uniform dispersion of PtRu catalyst, and small PtRu nanoparticles on the CNC. In DMFC single-cell tests, the PtRu/CNC-Ppy750 exhibited higher performance, approximately 1.7 times higher than PtRu/CB. In conclusion, the PtRu/CNC-PPy750 represents a promising electrocatalyst candidate for MOR and anodic DMFC applications.
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Cancer immunotherapy offers significant clinical benefits for patients with advanced or metastatic tumors. However, immunotherapeutic efficacy is often hindered by the tumor microenvironment's high redox levels, leading to variable patient outcomes. Herein, a therapeutic liposomal gold nanocage (MGL) is innovatively developed based on photo-triggered hyperthermia and a releasable strategy by combining a glutathione (GSH) depletion to remodel the tumor immune microenvironment, fostering a more robust anti-tumor immune response. MGL comprises a thermosensitive liposome shell and a gold nanocage core loaded with maleimide. The flexible shell promotes efficient uptake by cancer cells, enabling targeted destruction through photothermal therapy while triggering immunogenic cell death and the maturation of antigen-presenting cells. The photoactivated release of maleimide depletes intracellular GSH, increasing tumor cell sensitivity to oxidative stress and thermal damage. Conversely, GSH reduction also diminishes immunosuppressive cell activity, enhances antigen presentation, and activates T cells. Moreover, photothermal immunotherapy decreases elevated levels of heat shock proteins in tumor cells, further increasing their sensitivity to hyperthermia. In summary, MGL elicited a robust systemic antitumor immune response through GSH depletion, facilitating an effective photothermal immunotherapeutic strategy that reprograms the tumor microenvironment and significantly inhibits primary and metastatic tumors. This approach demonstrates considerable translational potential and clinical applicability.
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Controlling the structure and functionality of porous silica nanoparticles has been a continuous source of innovation with important potential for advanced biomedical applications. Their synthesis, however, usually involves passive surfactants or amphiphilic copolymers that do not add value to the material after synthesis. In contrast, polyion complex (PIC) micelles based on hydrophilic block copolymers allow for the direct synthesis of intrinsically functional hybrid materials. While most previous studies have focused on bulk materials made from double-hydrophilic block copolymers (DHBC), in this work we have synthesized a triple-hydrophilic block copolymer (THBC) and demonstrated both its PIC micellization and its potential for hybrid mesoporous silica nanomaterials. Introducing this THBC has allowed to direct the transition from bulk three-dimensional (3D) materials to zero-dimensional (0D) nanomaterials with cage-type structures. The stabilization and isolation of these nanostructures formed around discrete individual micelles has been made possible by the careful design of the three different blocks that each play a key role. These nanostructures could also be synthesized from hybrid PIC micelles based on THBC-multivalent metal ions complexes, offering a direct route to metal/silica composite nanoparticles. This class of THBC polymers therefore creates significant opportunities for the synthesis of nanostructures with complex and functional architectures.
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Metal nanocages exhibit localized surface plasmon resonance that strongly absorbs and scatters light at specific wavelengths, making them potentially valuable for photothermal therapy and biological imaging applications. However, investigations on metal nanocages are still confined to high-cost and small-scale synthesis. The comprehensive analysis of optical properties and optimal size parameters of metal nanocages is rarely reported. This paper simulates the effects of materials (Ag, Au, and Cu), size parameters, refractive index of the surrounding medium, and orientation on the light absorption and scattering characteristics of the nanocages using the finite-element method and the size-dependent refractive-index model for metal nanoparticles. The results show that the Ag nanocages have excellent light absorption and scattering characteristics and respond significantly to the size parameters, while the refractive index and orientation of the surrounding medium have less effect on them. The Au nanocages also possess superior light absorption properties at specific incident wavelengths. This study also identified the optimized sizes of three metal nanocages at incident light wavelengths commonly used in biomedicine; it was also found that, under deep therapy conditions, Ag nanocages in particular exhibit the highest volume absorption and scattering coefficients of 0.708 nm-1 and 0.583 nm-1, respectively. These findings offer theoretical insights into preparing target nanocage particles for applications in photothermal therapy and biological imaging.
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Designing efficient catalysts for operating CO2 electroreduction in membrane electrode assembly (MEA) faces significant obstacles. Herein, we propose an asymmetrically coordinated Ni SAC featuring axial Br coordination at NiN4Br sites anchoring onto hollow Br/N co-doped carbon nanocages, achieved through a NaBr-assisted confined-pyrolysis strategy. The Ni-NBr-C exhibits a high CO Faradaic efficiency (FECO> 97%) over the current density range of 50 to 350 mA cm-2 in the MEA device. Furthermore, Ni-NBr-C shows a stable cell voltage of 2.66 ± 0.2 V while delivering a large current density of 350 mA cm-2 over an 85-hour long-term operation, demonstrating its potential for industrial-scale applications. Advanced characterization techniques and theoretical calculations reveal that the coordination and doping of Br enhance the intrinsic activity but also highlighted that the unique pore structure improves mass transfer efficiency.
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A new and highly sensitive voltammetric technique was described in this study for the concurrent detection of endocrine disruptors bisphenol A (BPA) and bisphenol AF (BPAF) based on carbon nanocages (CNCs) and copper oxide nanochains (CuONCs). The CNCs was prepared by the solvothermal method and characterized using various techniques. Utilizing the nanocomposite of CNCs and CuONCs, the voltammetric sensor demonstrated outstanding performance in detecting BPA and BPAF simultaneously with distinct oxidation peaks and increased current peaks. The voltammetric signals have linear relationships with the two bisphenols ranging from 0.500⯵M to 100⯵M with a detection limit of 0.16⯵M for BPA and 0.14⯵M for BPAF. The newly designed sensor showed reliable consistency, long-term durability and anti-interference ability, and performed well in analyzing real water samples, indicating great potential for environmental monitoring.
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Compuestos de Bencidrilo , Carbono , Cobre , Técnicas Electroquímicas , Disruptores Endocrinos , Fenoles , Contaminantes Químicos del Agua , Fenoles/análisis , Fenoles/química , Compuestos de Bencidrilo/análisis , Compuestos de Bencidrilo/química , Cobre/análisis , Cobre/química , Disruptores Endocrinos/análisis , Disruptores Endocrinos/química , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/química , Carbono/química , Técnicas Electroquímicas/métodos , Monitoreo del Ambiente/métodos , Límite de Detección , Nanocompuestos/química , FluorocarburosRESUMEN
Ferritin (Ft) is a protein with a peculiar three-dimensional architecture. It is characterized by a hollow cage structure and is responsible for iron storage and detoxification in almost all living organisms. It has attracted the interest of the scientific community thanks to its appealing features, such as its nano size, thermal and pH stability, ease of functionalization, and low cost for large-scale production. Together with high storage capacity, these properties qualify Ft as a promising nanocarrier for the development of delivery systems for numerous types of biologically active molecules. In this paper, we introduce the basic structural and functional aspects of the protein, and summarize the methods employed to load bioactive molecules within the ferritin nanocage.
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Ferritinas , Nanopartículas , Ferritinas/química , Nanopartículas/química , Humanos , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , AnimalesRESUMEN
Ferritins are natural proteins which spontaneously self-assemble forming hollow nanocages physiologically deputed to iron storage and homeostasis. Thanks to their high stability and easy production in vitro, ferritins represent an intriguing system for nanobiotechnology. Here we investigated the mechanism of disassembly and reassembly of a human recombinant ferritin constituted by the heavy chain (hHFt) exploiting a new procedure which involves the use of minimal amounts of sodium dodecyl sulfate (SDS) and assessed its effectiveness in comparison with two commonly used protocols based on pH shift at highly acidic and alkaline values. The interest in this ferritin as drug nanocarrier is related to the strong affinity of the human H-chain for the transferrin receptor TfR-1, overexpressed in several tumoral cell lines. Using different techniques, like NMR, TEM and DLS, we demonstrated that the small concentrations of SDS can eliminate the nanocage architecture without detaching the monomers from each other, which instead remain strongly associated. Following this procedure, we encapsulated into the nanocage a small ruthenium complex with a remarkable improvement with respect to previous protocols in terms of yield, structural integrity of the recovered protein and encapsulation efficiency. In our opinion, the extensive network of interchain interactions preserved during the SDS-based disassembly procedure represents the key for a complete and correct hHFt reassembly.
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Portadores de Fármacos , Ferritinas , Humanos , Ferritinas/química , Portadores de Fármacos/química , Receptores de Transferrina/metabolismo , Receptores de Transferrina/química , Nanopartículas/química , Sistemas de Liberación de Medicamentos , Concentración de Iones de Hidrógeno , Proteínas Recombinantes/química , Dodecil Sulfato de Sodio/química , Antígenos CDRESUMEN
Layered double hydroxides (LDHs) have attracted significant attention due to their compositional and structural flexibility. However, it is challenging but meaningful to design and fabricate hierarchical mixed-dimensional LDHs with synergistic effects to increase the electrical conductivity of LDHs and promote the intrinsic activity. Herein, 3D hollow NiCo-LDH nanocages decorated porous biochar (3D NiCo-LDH/PBC) has been synthesized by using ZIF-67 as precursor, which was utilized for constructing electrochemical sensing platform to realize simultaneous determination of Cu2+ and Hg2+. The 3D NiCo-LDH/PBC possessed the characteristics of hollow material and three-dimensional porous material, revealing a larger surface area, more exposed active sites, and faster electron transfer, which is beneficial to enhancing its electrochemical performance. Consequently, the developed sensor displayed good performance for simultaneously detecting Cu2+ and Hg2+ with ultra-low limit of detection (LOD) of 0.03 µg L-1 and 0.03 µg L-1, respectively. The proposed sensor also demonstrated excellent stability, repeatability and reproducibility. Furthermore, the sensor can be successfully used for the electrochemical analysis of Cu2+ and Hg2+ in lake water sample with satisfactory recovery, which is of great feasibility for practical application.
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The exploitation of hierarchical carbon nanocages with superior light-to-heat conversion efficiency, together with their distinct structural, morphological, and electronic properties, in photothermal applications could provide effective solutions to long-standing challenges in diverse areas. Here, we demonstrate the discovery of pristine and nitrogen-doped hierarchical carbon nanocages as superior supports for highly loaded, small-sized Ru particles toward enhanced photothermal CO2 catalysis. A record CO production rate of 3.1 mol·gRu-1·h-1 with above 90% selectivity in flow reactors was reached for hierarchical nitrogen-doped carbon-nanocage-supported Ru clusters under 2.4 W·cm-2 illumination without external heating. Detailed studies reveal that the enhanced performance originates from the strong broadband sunlight absorption and efficient light-to-heat conversion of nanocage supports as well as the excellent intrinsic catalytic reactivity of sub-2 nm Ru particles. Our study reveals the great potential of hierarchical carbon nanocages in photothermal catalysis to reduce the fossil fuel consumption of various industrial chemical processes and stimulates interest in their exploitation for other demanding photothermal applications.
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A novel biofuel cell (BFC)-based self-powered electrochemical immunosensing platform was developed by integrating the target-induced biofuel release and biogate immunoassay for ultrasensitive 17ß-estradiol (E2) detection. The carbon nanocages/gold nanoparticle composite was employed in the BFCs device as the electrode material, through which bilirubin oxidase and glucose oxidase were wired to form the biocathode and bioanode, respectively. Positively charged mesoporous silica nanoparticles (PMSN) were encapsulated with glucose molecules as biofuel and subsequently coated by the negatively charged AuNPs-labelled anti-E2 antibody (AuNPs-Ab) serving as a biogate. The biogate could be opened efficiently and the trapped glucose released once the target E2 was recognized and captured by AuNPs-Ab due to the decreased adhesion between the antigen-antibody complex and PMSN. Then, glucose oxidase oxidized the glucose to produce a large number of electrons, resulting in significantly increased open-circuit voltage (EOCV). Promisingly, the proposed BFC-based self-powered immunosensor demonstrated exceptional sensitivity for the detection of E2 in the concentration range from 1.0 pg mL-1 to 10.0 ng mL -1, with a detection limit of 0.32 pg mL-1 (S/N = 3). Furthermore, the prepared BFC-based self-powered homogeneous immunosensor showed significant potential for implementation as a viable prototype for a mobile and an on-site bioassay system in food and environmental safety applications.
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Fuentes de Energía Bioeléctrica , Técnicas Biosensibles , Estradiol , Glucosa Oxidasa , Oro , Límite de Detección , Nanopartículas del Metal , Inmunoensayo/métodos , Estradiol/química , Estradiol/análisis , Oro/química , Glucosa Oxidasa/química , Técnicas Biosensibles/métodos , Nanopartículas del Metal/química , Técnicas Electroquímicas/métodos , Técnicas Electroquímicas/instrumentación , Humanos , Electrodos , Glucosa/análisis , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/química , Anticuerpos Inmovilizados/inmunología , Dióxido de Silicio/química , Enzimas Inmovilizadas/químicaRESUMEN
Cervical cancer is one of the most common gynecological malignancies, with the vast majority of which being caused by persistent infection with Human Papillomavirus (HPV) 16 and 18. The current available HPV detection methods are sensitive and genotyped but are restricted by expensive instruments and skilled personnel. The development of an easy-to-use, rapid, and cost-friendly analysis method for HPV is of great need. Herein, hollow palladium-ruthenium nanocages modified with two oligonucleotides (PdRu capture probes) were constructed for genotyping and simultaneous detection of target nucleic acids HPV16 and HPV18 by dual lateral flow assay (DLFA). PdRu capture probes were endowed with bi-functions for the first time, which could be used to output signals and hybridize target nucleic acids. Under optimized conditions, the PdRu based-DLFA with detection limits of 0.93 nM and 0.19 nM, respectively, exhibited convenient operation, and high sensitivity. Meanwhile, the DLFA achieved excellent rapid detection within 20 min, which was attributed to capture probes that can be directly bound to amplification-free target nucleic acids. Therefore, the development of PdRu-based DLFA can be utilized for rapid, sensitive, and simultaneous genotyping detection of HPV16 and HPV18, showing great application for nucleic acid detection.
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Papillomavirus Humano 16 , Papillomavirus Humano 18 , Paladio , Paladio/química , Humanos , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/aislamiento & purificación , Rutenio/química , Nanoestructuras/química , ADN Viral/análisis , ADN Viral/genética , Propiedades de Superficie , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Límite de Detección , Tamaño de la Partícula , Hibridación de Ácido Nucleico , Virus del Papiloma HumanoRESUMEN
Cancer immunotherapy remains a significant challenge due to insufficient proliferation of immune cells and the sturdy immunosuppressive tumor microenvironment. Herein, we proposed the hypothesis of cuproptosis-lactate regulation to provoke cuproptosis and enhance anti-tumor immunity. For this purpose, copper-human serum albumin nanocomplex loaded gold nanocages with bacterial membrane coating (BAu-CuNCs) were developed. The targeted delivery and disassembly of BAu-CuNCs in tumor cells initiated a cascade of reactions. Under near infrared (NIR) laser irradiation, the release of copper-human serum albumin (Cu-HSA) was enhanced that reacted with intratumoral glutathione (GSH) via a disulfide exchange reaction to liberate Cu2+ ions and exert cuproptosis. Subsequently, the cuproptosis effect triggered immunogenic cell death (ICD) in tumor by the release of damage associated molecular patterns (DAMPs) to realize anti-tumor immunity via robust production of cytotoxic T cells (CD8+) and helper T cells (CD4+). Meanwhile, under NIR irradiation, gold nanocages (AuNCs) promoted excessive reactive oxygen species (ROS) generation that played a primary role in inhibiting glycolysis, reducing the lactate and ATP level. The combine action of lower lactate level, ATP reduction and GSH depletion further sensitized the tumor cells to cuproptosis. Also, the lower lactate production led to the significant blockage of immunosuppressive T regulatory cells (Tregs) and boosted the anti-tumor immunity. Additionally, the effective inhibition of breast cancer metastasis to the lungs enhanced the anti-tumor therapeutic impact of BAu-CuNCs + NIR treatment. Hence, BAu-CuNCs + NIR concurrently induced cuproptosis, ICD and hindered lactate production, leading to the inhibition of tumor growth, remodeling of the immunosuppressive tumor microenvironment and suppression of lung metastasis. Therefore, leveraging cuproptosis-lactate regulation, this approach presents a novel strategy for enhanced tumor immunotherapy.
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Cobre , Oro , Inmunoterapia , Ácido Láctico , Albúmina Sérica Humana , Oro/química , Cobre/química , Inmunoterapia/métodos , Humanos , Animales , Albúmina Sérica Humana/química , Albúmina Sérica Humana/administración & dosificación , Ácido Láctico/química , Femenino , Neoplasias/terapia , Neoplasias/inmunología , Línea Celular Tumoral , Ratones Endogámicos BALB C , Nanopartículas del Metal/administración & dosificación , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Materiales Biomiméticos/química , Microambiente Tumoral , Especies Reactivas de Oxígeno/metabolismo , Glutatión/metabolismo , RatonesRESUMEN
Multidrug resistance (MDR) is a major obstacle limiting the effectiveness of chemotherapy against cancer. The combination strategy of chemotherapeutic agents and siRNA targeting drug efflux has emerged as an effective cancer treatment to overcome MDR. Herein, stimuli-responsive programmable tetrahedral DNA-RNA nanocages (TDRN) have been rationally designed and developed for dynamic co-delivery of the chemotherapeutic drug doxorubicin and P-glycoprotein (P-gp) siRNA. Specifically, the sense and antisense strand sequences of the P-gp siRNA, which are programmable bricks with terminal disulfide bond conjugation, are precisely embedded in one edge of the DNA tetrahedron. TDRN provides a stimuli-responsive release element for dynamic control of functional cargo P-gp siRNA that is significantly more stable than the "tail-like" TDN nanostructures. The stable and highly rigid 3D nanostructure of the siRNA-organized TDRN nanocages demonstrated a notable improvement in the stability of RNase A and mouse serum, as well as long-term storage stability for up to 4 weeks, as evidenced by this study. These biocompatible and multifunctional TDRN nanocarriers with gold nanocluster-assisted delivery (TDRN@Dox@AuNCp) are successfully used to achieve synergistic RNAi/Chemo-therapy in vitro and in vivo. This programmable TDRN drug delivery system, which integrates RNAi therapy and chemotherapy, offers a promising approach for treating multidrug-resistant tumors.
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ADN , Doxorrubicina , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , ARN Interferente Pequeño , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/química , Animales , Ratones , Resistencia a Antineoplásicos/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Doxorrubicina/farmacología , Resistencia a Múltiples Medicamentos/genética , Resistencia a Múltiples Medicamentos/efectos de los fármacos , ADN/genética , ADN/química , Humanos , Nanoestructuras/química , Línea Celular Tumoral , Modelos Animales de Enfermedad , Neoplasias/genética , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Sistemas de Liberación de Medicamentos/métodos , Ratones DesnudosRESUMEN
The developments of mixed matrix membranes (MMMs) are severely hindered by the complex inter-phase interaction and the resulting poor utilization of inorganics' microporosity. Herein, a dual porosity framework is constructed in MMMs to enhance the accessibility of inorganics' microporosity to external gas molecules for the effective application of microporosity for gas separation. Nanocomposite organogels are first prepared from the supramolecular complexation of rigid polymers and 2 nm microporous coordination nanocages (CNCs). The network structures can be maintained with microporous features after solvent removal originated from the rigid nature of polymers, and the strong coordination and hydrogen bond between the two components. Moreover, the strong supramolecular attraction reinforces the frustrated packing of the rigid polymers on CNC surface, leading to polymer networks' extrinsic pores and the interconnection of CNCs' micro-cavities for the fast gas transportation. The gas permeabilities of the MMMs are 869 times for H2 and 1099 times for CO2 higher than those of pure polymers. The open metal sites from nanocage also contribute to the enhanced gas selectivity and the overall performance surpasses 2008 H2/CO2 Robeson upper bound. The supramolecular complexation reinforced packing frustration strategy offers a simple and practical solution to achieve improved gas permselectivity in MMMs.
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With the rapid development of anion exchange membrane technology and the availability of high-performance non-noble metal cathode catalysts in alkaline media, the commercialization of anion exchange membrane fuel cells has become feasible. Currently, anode materials for alkaline anion-exchange membrane fuel cells still rely on platinum-based catalysts, posing a challenge to the development of efficient low-Pt or Pt-free catalysts. Low-cost ruthenium-based anodes are being considered as alternatives to platinum. However, they still suffer from stability issues and strong oxophilicity. Here, we employ a metal-organic framework compound as a template to construct three-dimensional porous ruthenium-tungsten-zinc nanocages via solvothermal and high-temperature pyrolysis methods. The experimental results demonstrate that this porous ruthenium-tungsten-zinc nanocage with an electrochemical surface area of 116 m2 g-1 exhibits excellent catalytic activity for hydrogen oxidation reaction in alkali, with a kinetic density 1.82 times and a mass activity 8.18 times higher than that of commercial Pt/C, and a good catalytic stability, showing no obvious degradation of the current density after continuous operation for 10,000 s. These findings suggest that the developed catalyst holds promise for use in alkaline anion-exchange membrane fuel cells.
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SARS-CoV-2 virus variants of concern (VOCs) have rapidly changed their transmissibility and pathogenicity primarily through mutations in the structural proteins. Herein, we present molecular details with dynamics of the ferritin nanocages stitched with synthetic chimeras displaying the Spike receptor binding domains (RBDs). Our findings demonstrated the potential usage of ferritin-based vaccines that may effectively inhibit viral entry by blocking the Spike-ACE2 network and may induce cross-protective antibody responses. Taking the nanocage constructs into consideration, we evaluated the effects of variants on the docked interface of the SARS-CoV-2 Spike RBD with the ACE2 (angiotensin-converting enzyme 2) host cell receptor and neutralizing antibodies (Abs). Investigating the VOCs revealed that most of the mutations reported a possibly reduced structural stability within the Spike RBD domain. Point mutations have moderate or no effect for VVH-72, CR3022, and S309 Abs when bound with the Spike RBD, whereas a significant effect was observed for B38, CB6, and m396 over the surface of the H-ferritin nanocage. In addition to providing useful therapeutic approaches against COVID-19 (coronavirus disease 2019), these structural details can also be used to fight future coronavirus outbreaks.
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BACKGROUND: Microcystin-leucine-arginine (MC-LR) produced by various cyanobacteria during harmful algal bloom poses serious threats to drinking water safety and human health. Conventional chromatography-based detection methods require expensive instruments and complicated sample pretreatment, limiting their application for on-site detection. Colorimetric aptasensors are simple and rapid, and are amenable to fast detection. However, they provide only one output signal, resulting in poor sensitivity and accuracy. Dual-channel ratiometric colorimetric method based on the peroxidase-like activity of nanozyme can achieve self-calibration by recording two reverse signals, providing significantly enhanced sensitivity and accuracy. RESULTS: CeO2 nanocages (CeO2 NCs) with tetra-enzyme mimetic activities (oxidase-, peroxidase-, catalase- and superoxide dismutase-like activities) were facilely synthesized using zeolitic imidazolate framework-67 (ZIF-67) as sacrificial template. The peroxidase-like activity of CeO2 NCs can be regulated by DNA, and it showed opposite response to two chromogenic substrates (2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and 3,3',5,5'-tetramethylbenzidine (TMB)), which was mainly attributed to the changed affinity. On the basis of MC-LR aptamer-tunable peroxidase-like activity of CeO2 NCs in TMB and ABTS channel, a dual-channel ratiometric colorimetric aptasensor was constructed for detection of MC-LR. Compared with conventional single-signal colorimetric assays, the proposed method showed lower limit of detection (0.66 pg mL-1) and significantly enhanced sensitivity. Moreover, the practicability of the ratiometric colorimetric assay was demonstrated by detecting MC-LR in real water samples, and satisfactory recoveries (94.9-101.9 %) and low relative standard deviations (1.6-6.3 %) were obtained. SIGNIFICANCE: This work presents a nanozyme-based ratiometric colorimetric aptasensor for MC-LR detection by recording the reverse responses of two chromogenic reactions. Benefiting from the self-calibration function, the method can achieve higher sensitivity and accuracy. The short detection time and practical application in real water samples show great potential for environmental monitoring.
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Cerio , Colorimetría , Toxinas Marinas , Microcistinas , Microcistinas/análisis , Colorimetría/métodos , Toxinas Marinas/análisis , Cerio/química , Aptámeros de Nucleótidos/química , Límite de Detección , Nanoestructuras/química , Técnicas Biosensibles/métodosRESUMEN
Non-small cell lung cancer (NSCLC) caused more deaths in 2017 than breast cancer, prostate, and brain cancers combined. This is primarily due to their aggressive metastatic nature, leading to more fatal rates of cancer patients. Despite this condition, there are no clinically approved drugs that can target metastasis. The NSCLC with EGFR T790M-overexpressing HER2 shows the resistance to osimertinib and trastuzumab starting 10-18 months after the therapy, and thus prospects are grim to these patients. To target the recalcitrant ERBB2 driver oncogene, we developed two engineered destabilizing 3'UTR ERBB2 constructs that degrade the endogenous ERBB2 transcript and proteins by overwriting the encoded endogenous ERBB2 mRNA with the destabilizing message. When iron oxide nanocages (IO nanocages) were used as vehicles to deliver them to tumors and whole tissues in mice bearing tumors, it was well tolerated and safe and caused no genome rearrangement whereas they were integrated into genome deserts (non-coding regions). We achieved significant reduction of the primary tumor volume with desARE3'UTRERBB2-30, achieving 50% complete tumor lysis and inhibiting 60%-80% of liver metastasis, hepatomegaly, and 90% of lung metastasis, through ERBB2 downregulation. These constructs were distributed robustly into tumors, livers, lungs, kidneys, and spleen and mildly in the brain and not in the heart. They caused no abnormality in both short- and long-term administrations as well as in healthy mice. In summary, we accomplished significant breakthrough for the therapeutics of intractable lung cancer patients whose cancers become resistant and metastasize.