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Extracellular histones are crucial damage-associated molecular patterns involved in the development and progression of multiple critical and inflammatory diseases, such as sepsis, pancreatitis, trauma, acute liver failure, acute respiratory distress syndrome, vasculitis and arthritis. During the past decade, the physiopathologic mechanisms of histone-mediated hyperinflammation, endothelial dysfunction, coagulation activation, neuroimmune injury and organ dysfunction in diseases have been systematically elucidated. Emerging preclinical evidence further shows that anti-histone strategies with either their neutralizers (heparin, heparinoids, nature plasma proteins, small anion molecules and nanomedicines, etc.) or extracorporeal blood purification techniques can significantly alleviate histone-induced deleterious effects, and thus improve the outcomes of histone-related critical and inflammatory animal models. However, a systemic evaluation of the efficacy and safety of these histone-targeting therapeutic strategies is currently lacking. In this review, we first update our latest understanding of the underlying molecular mechanisms of histone-induced hyperinflammation, endothelial dysfunction, coagulopathy, and organ dysfunction. Then, we summarize the latest advances in histone-targeting therapy strategies with heparin, anti-histone antibodies, histone-binding proteins or molecules, and histone-affinity hemoadsorption in pre-clinical studies. Finally, challenges and future perspectives for improving the clinical translation of histone-targeting therapeutic strategies are also discussed to promote better management of patients with histone-related diseases.
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Histonas , Inflamación , Humanos , Histonas/metabolismo , Animales , Inflamación/inmunología , Inflamación/terapia , Enfermedad Crítica , Heparina/uso terapéuticoRESUMEN
Objective: To design and prepare a high efficiency bilirubin adsorbent with good mechanical properties and biocompatibility. Methods: In this study, quaternary ammonium pyridine was designed and synthesized, and then modified polyether sulfone microspheres, or PES/p(4-VP-co-N-VP)@6 microspheres, were prepared by phase conversion and electrostatic spraying. The morphology of the polymer components and the microspheres were studied by means of nuclear magnetic resonance (NMR) spectroscopy and scanning electron microscopy. The basic properties of the microspheres and their bilirubin adsorption efficiency were tested, and the adsorption mechanism was further explored. Blood cell counts and the clotting time of the microspheres were also measured. Results: The diameter of the modified polyether sulfone microspheres prepared in the study was approximately 700-800 µm. Compared with the original PES microspheres, the surface and internal structure of PES/p(4-VP-co-N-VP)@6 microspheres did not change significantly, and they also had a loose porous structure, with some micropores scattered around in addition to irregular large pores. Compared with the control group, the bilirubin removal effect of the modified microspheres was (94.91±0.73)% after static adsorption in bilirubin PBS buffer solution for 180 min, with the difference being statistically significant (P<0.0001). According to the findings for the clotting time, the activated partial thromboplastin time (APTT) of the blank plasma group, the control PES group, and the modified PES microsphere group were (27.57±1.25) s, (28.47±0.45) s, and (30.4±0.872) s, respectively, and the difference between the experimental group and the other two groups was statistically significant (P<0.01, P<0.05). There was no significant change in red blood cell and white blood cell counts. Conclusion: The microspheres prepared in the study have high efficiency in bilirubin adsorption, excellent mechanical properties and thermal stability, and good blood biocompatibility, and are expected to be used in the clinical treatment of patients with liver failure.
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Bilirrubina , Microesferas , Polímeros , Sulfonas , Sulfonas/química , Polímeros/química , Adsorción , Bilirrubina/sangre , HumanosRESUMEN
Periprosthetic infection and mechanical loosening are two leading causes of implant failure in orthopedic surgery that have devastating consequences for patients both physically and financially. Hence, advanced prostheses to simultaneously prevent periprosthetic infection and promote osseointegration are highly desired to achieve long-term success in orthopedics. In this study, we proposed a multifunctional three-dimensional printed porous titanium alloy prosthesis coated with imidazolium ionic liquid. The imidazolium ionic liquid coating exhibited excellent bacterial recruitment property and near-infrared (NIR) triggered photothermal bactericidal activity, enabling the prosthesis to effectively trap bacteria in its vicinity and kill them remotely via tissue-penetrating NIR irradiation. In vivo anti-infection and osseointegration investigations in infected animal models confirmed that our antibacterial prosthesis could provide long-term and sustainable prevention against periprosthetic infection, while promoting osseointegration simultaneously. It is expected to accelerate the development of next-generation prostheses and improve patient outcomes after prosthesis implantation.
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Endotoxin adsorption has received extensive attention in the field of blood purification. However, developing highly efficient endotoxin adsorbents with excellent hemocompatibility remains challenging. In this study, we propose a new approach for developing the functional polyethersulfone (PES) membrane to remove endotoxins. First, the PES polymer is grafted with polyethylene glycol methyl acrylate (PEG-MA) in a homogeneous phase system via γ irradiation, and PES-g-PEG can be directly used to prepare the membrane by the phase inversion method. Then, polydopamine (PDA) is coated as an adhesive layer onto a PES-g-PEG membrane in an alkaline aqueous solution, and lysozyme (Lyz) is covalently immobilized with PDA through the Schiff base reaction. Lysozyme acts as an affinity adsorption ligand of endotoxin through charge and hydrophobic action. Our study reveals that the PEG branched chain and the PDA coating on the PES membrane can maintain the secondary structure of lysozyme, and thus, the immobilized Lyz can maintain high activity. The adsorption capacity of endotoxins for the PES-g-PEG/PDA/Lyz membrane is 1.28 EU/mg, with an equilibrium adsorption time of 6 h. Therefore, the PES-g-PEG/PDA/Lyz membrane shows great potential application in the treatment of endotoxemia.
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Endotoxinas , Muramidasa , Sulfonas , PolietilenglicolesRESUMEN
Correction for 'Intelligent antibacterial surface based on ionic liquid molecular brushes for bacterial killing and release' by Lunqiang Jin et al., J. Mater. Chem. B, 2019, 7, 5520-5527, https://doi.org/10.1039/C9TB01199D.
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Oil spills and pollution of oily wastewater from the industrial field have not only caused serious economic losses but also imposed a huge threat to human beings. To solve these issues, the development of advanced materials and technologies for the purification of oily wastewater has garnered great concern and become a central topic. Hence, a superhydrophobic polyurethane (PU) sponge adsorbent is designed via mussel-inspired coatings by double bonds to PU sponge, followed by in situ polymerization with 1-hexadecene. The prepared PU sponge adsorbent (PU@DB@16ene sponge) showed outstanding mechanical properties including low density, high porosity, and compression recovery ability. Moreover, the prepared PU@DB@16ene sponge showed excellent adsorption of oils and organic solvents (up to 187 g g-1) and exhibited superior recyclability. Particularly, when the PU@DB@16ene sponge was applied in the continuous and rapid separation of oils and organic solvents, it still showed desired properties at a rapid velocity of 8.3 L m-3 s-1. Additionally, the PU@DB@16ene sponge could not only adsorb organic solvents in laboratories but also adsorb crude oil and industrial waxy oil in practice. Therefore, we proposed a simple and convenient method to construct PU sponge absorbents with great application prospects, which would be highly valuable for crude oil and organic solvents cleanup.
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In this work, enhanced guest-pair interactions in the cavity of cucurbit[8]uril (CB[8]) are quantitatively determined using single-molecule force spectroscopy (SMFS). Significantly, the light-driven dynamic conformational change of guest pairs leads to a rupture force switching between the connected and broken CB[8]-mediated heteroternary complexation with viologen and bis(azobenzene) derivatives. SMFS is further utilized to detect methyl viologen based on the competitive host-guest interaction toward the guest in CB[8] or CB[7]. These findings highlight the extraordinary power of SMFS in supramolecular chemistry and will contribute to the fundamental understanding of the mechanochemical behavior of host-guest interactions.
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Multi stimuli-responsive polymersomes are in high demand as smart drug carriers, particularly for the treatment of complex cancers. However, most polymersomes have multi-responsiveness that does not affect each other and focus on single drug loading. Here, we have designed photo-crosslinked temperature and pH dual-responsive polymersomes by the self-assembly of a triblock polymer of methoxyl poly(ethylene glycol)-b-poly(N-isopropylacrylamide)-b-poly[2-(diethylamino)ethyl methacrylate-co-2-hydroxy-4-(methacryloyloxy)benzophenone] (mPEG-b-PNIPAM-b-P(DEAEMA-co-BMA)) synthesized via reversible addition-fragmentation chain transfer polymerization (RAFT). The dual-responsive polymersomes had a layered membrane, resulting in tunable permeability. Importantly, the polymersomes were proved to have a pH-controlled temperature-responsiveness. A hydrophilic-hydrophobic drug pair (doxorubicin hydrochloride, DOX, and paclitaxel, PTX) could be co-encapsulated in the fabricated polymersomes. The membrane permeability based on its layered structure was triggered by the change in temperature and pH to permit the separate control on the release of DOX and PTX. In a simulated tumor microenvironment, DOX and PTX encapsulated in the polymersomes could take effect for a relatively longer period and could work synergistically. Thus, the photo-crosslinked and dual-responsive polymersomes can be considered as promising drug carriers in the field of tumor combination chemotherapy.
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Antibióticos Antineoplásicos/farmacología , Antineoplásicos Fitogénicos/farmacología , Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos , Paclitaxel/farmacología , Polímeros/química , Animales , Antibióticos Antineoplásicos/química , Antineoplásicos Fitogénicos/química , Materiales Biocompatibles/síntesis química , Materiales Biocompatibles/química , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Reactivos de Enlaces Cruzados/síntesis química , Reactivos de Enlaces Cruzados/química , Doxorrubicina/química , Portadores de Fármacos/síntesis química , Portadores de Fármacos/química , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Concentración de Iones de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Ratones , Estructura Molecular , Paclitaxel/química , Tamaño de la Partícula , Polímeros/síntesis química , Propiedades de Superficie , Temperatura , Microambiente Tumoral/efectos de los fármacosRESUMEN
Functionalized sponge adsorbent was prepared by a mussel-inspired strategy, which achieved successive modification of material and remained the properties of substrate. The dopamine derivative, DOPAm, was synthesized and adhered to polyurethane (PU) sponge before in situ polymerization with sodium p-styrenesulfonate. The adsorbent showed superior removal efficiency for cationic dyes (98.9 % for methylene blue (MB) at the concentration of 200 µmol/L); it took 1 s only for the adsorbent to adsorb the dyes by swelling and squeezing out the bulk solution simply. Meanwhile, the superior adsorption effect of the adsorbent could be maintained in a wide range of solution pH values from 1 to 13 at room temperature (293 K) in several repeat experiments, due to the slight influence of strong acid and alkali on polysulfonate. With unchanged other experimental conditions, the removal efficiency is still more than 90 % after reusing for 10 times at the different concentrations of MB dye solutions (50, 100, 200 µmol/L). For large-scale wastewater treatment, with the removal efficiency of 80.0 %, the adsorbent could purify 4.1 L wastewater containing MB dye (100 µmol/L) with the maximum flux of 22.2 L/(m3·s) without the assistance of any equipment except for a vacuum pump. Therefore, the adsorbent has great possibilities to be applied in high-efficient and convenient treatment of wastewater in a large scale.
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A novel ion species-responsive oil-water separation material was designed: poly ionic liquid (PIL) was carried on the graphene oxide (GO) by free radical polymerization, then the PIL modified GO sheets (GO-PIL) were coated on cotton fabric (CF). The wettability of the obtained GO-PIL coated CF (GO-PIL@CF) could be switched between hydrophilic and hydrophobic state with the exchange of different types of counteranions. Water contact angle of the GO-PIL@CF could be switched between 0 to about 145°; and correspondingly the underwater oil contact angle would change between about 148 to 0°. Because of the switchable wettability, the GO-PIL@CF could selectively separate water or oil from the oil-water mixtures. Meanwhile, due to the loose fibrous structure, the GO-PIL@CF showed relatively high permeate fluxes; in the hydrophilic state the water flux was about 36000 L/m2h, while in the hydrophobic state the fluxes for the low-density oils (n-hexane and toluene) were about 59,000 and 65000 L/m2h, respectively. Consequently, the separation processes could be completed simply by gravity. In addition, because of the soft and flexible mechanical property, the GO-PIL@CF could serve as wrappage of traditional absorbents and be applied directly as absorbent to remove water or oil selectively from their mixtures.
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Macrocyclic cucurbit[n]uril (CB[n]) molecules have triggered renewed interest because of their outstanding capabilities as host molecules to selectively interact with a wide range of small guest molecules. Here, CB[7]-based host-guest interactions were investigated for a guest-modified nanoelectrode by monitoring the electrochemical current. A ferrocene (Fc)-terminated molecule immobilized on a gold nanoelectrode (GNE) showed suitable affinity with CB[7] when the effective exposing area of the GNE was between 5.3 and 12 µm2 and the bias applied on the GNE was -500 mV. Monitoring the dynamics of nanoparticles (NPs) on a nanoelectrode provides new insights into the host-guest interactions at molecular interfaces.
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Pathogen capture and removal from whole blood is a new strategy for extracorporeal blood purification, especially in initial treatment of sepsis before pathogen identification. Herein, hemocompatible magnetic particles with broad-spectrum bacteria capture capability were proposed for pathogen removal from whole blood, omitting the necessity of pathogen identification. Firstly, we designed and synthesized a new kind of imidazolium-based ionic liquid with good antibacterial activity, and polydopamine coating was utilized as a hemocompatible platform to immobilize ionic liquids on Fe3O4 nanoparticles, forming the hemocompatible magnetic particles (Fe3O4@PDA-IL). The magnetic particles exhibited good hemocompatibility and performed well in the removal of various species of clinically significant pathogens from human whole blood, including S. aureus, E. coli, and the hard-to-treat bacteria of P. aeruginosa and Methicillin-resistant S. aureus, which are the most common pathogens in bloodstream infections. Besides, the Fe3O4@PDA-IL particles were also capable to remove bacterial endotoxins from blood, inhibiting further aggravation of sepsis. Overall, we demonstrated the application of hemocompatible magnetic particles in the removal of pathogens and bacterial endotoxins from whole blood via electrostatic and hydrophobic interactions, without significant effects on blood cells or the activation of coagulation and complement, addressing the feasibility of using imidazolium-based ionic liquids for bacteria capture and removal from whole blood. It would contribute to the development of magnetic separation-based approaches to remove bacteria and bacterial endotoxin for extracorporeal blood purification, especially in initial sepsis therapy before pathogen identification.
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Staphylococcus aureus Resistente a Meticilina , Staphylococcus aureus , Bacterias , Escherichia coli , Humanos , Fenómenos MagnéticosRESUMEN
Current therapy for liver failure and concomitant hyperbilirubinemia faces the challenge of poor hemocompatibility and bleeding risks associated with the anticoagulant injection. Herein, heparin-mimetic biomacromolecule (HepMBm) with a similar degree of sulfation and anticoagulant properties to heparin was synthesized by imitating the structure of natural biomacromolecule heparin. Then HepMBm was used to prepare nanocomposite spheres based on reduced graphene oxide (rGO). The formation of a dual-network structure in the spheres endowed the spheres with improved dimensional stability. The proposed spheres exhibited outstanding blood compatibilities and excellent self-anticoagulant properties. The bilirubin adsorption experiments and whole blood bilirubin removal assay indicated that the spheres exhibited high bilirubin removal capability from whole blood (The removal ratio was 99.69%.). The spheres open new routes for a therapeutic strategy without a plasma separation system and heparin pump, which may be a step toward a lightweight wearable artificial liver.
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Hígado Artificial , Nanocompuestos , Dispositivos Electrónicos Vestibles , Anticoagulantes/farmacología , BilirrubinaRESUMEN
In this study, we proposed a green, facile and low-cost approach for the fabrication of multifunctional particles with robust bacteria removal capability and on-demand biofilm eradication activity. Based on mussel-inspired coating of catechol and hexanediamine on Fe3O4 in aqueous solution, magnetic poly(catechol-hexanediamine) particles (Fe3O4@HDA) were prepared successfully in 1 h, at room temperature. Microbiological experiments demonstrated the Fe3O4@HDA particles could capture bacteria in water efficiently. Meanwhile, with an integration of magnetic response property and near-infrared-triggered photothermal bactericidal activity, the Fe3O4@HDA particles showed a high potential for biofilm targeting and in-situ eradication. We believe that the rationally designed magnetic poly(catechol-hexanediamine) particles could extend the applications of smart antimicrobial agents to industrial fields such as water disinfection and biofouling clean-up.
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Biopelículas/efectos de los fármacos , Catecoles/farmacología , Diaminas/farmacología , Escherichia coli/aislamiento & purificación , Polímeros/farmacología , Staphylococcus aureus/aislamiento & purificación , Catecoles/química , Diaminas/química , Compuestos Férricos/química , Fenómenos Magnéticos , Tamaño de la Partícula , Polímeros/síntesis química , Polímeros/química , Propiedades de SuperficieRESUMEN
Postoperative adhesion may form as the result of a complicated fibrosis and inflammatory response, thus leads to a series of complications or increases the risk of surgery failure. Herein, we prepared poly (lactic-co-glycolic acid)-graft-polyvinylpyrrolidone/polyiodide (PLGA-g-PVP/I) electrospun fibrous membranes to prevent postoperative adhesion and infection formation. Firstly, hydrophilic PVP molecules were grafted on the surface of PLGA powders by gamma ray, and then iodine ions were coordinated with the grafted PVP. Subsequently, PLGA-g-PVP/I fibrous membranes were prepared by electrospinning. The PLGA-g-PVP/I membranes were analyzed via UV-vis, FTIR, Raman, and XPS. The formed polyiodide endowed the membranes with sustained antibacterial activity. The antimicrobial property of PLGA-g-PVP/I membranes was ascribed to the synergistic effect of intracellular ROS production and glutathione oxidation. Furthermore, the prevention efficacy of postoperative abdominal adhesion from the PLGA-g-PVP/I composite membranes was characterized in a rat model of sidewall defect-cecum abrasion. The results demonstrated that the PLGA-g-PVP/I fibrous membranes could prevent the postoperative abdominal adhesion effectively. Therefore, to endow the PLGA-g-PVP/I electrospun fibrous membranes with durable antibacterial property may be a promising strategy towards an anti-bacterial and anti-adhesion system for commercial and clinical uses.
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Antibacterianos/farmacología , Materiales Biocompatibles/farmacología , Escherichia coli/efectos de los fármacos , Ácido Peryódico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/farmacología , Povidona/química , Animales , Antibacterianos/química , Materiales Biocompatibles/química , Proliferación Celular/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Ratones , Pruebas de Sensibilidad Microbiana , Estrés Oxidativo/efectos de los fármacos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Ratas , Rayos UltravioletaRESUMEN
The prevention of bacteria-induced infections has been increasing in importance in both clinical surgery and biomedical engineering. Although great attention has been paid to designing intelligent antibacterial surfaces, the fabrication processes are still not facile and universal enough, and the antibacterial efficiencies of these surfaces are also not ideal. Herein, ionic liquid (IL) molecules of 3-(12-mercaptododecyl)-1-methyl-1H-imidazol-3-ium bromide (IL(Br)) were synthesized with the minimum inhibitory concentrations as low as 4 and 8 µg mL-1 against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), respectively. By simply immersing a polymeric substrate into the IL(Br) solution, an antibacterial surface with high killing efficiency of 99% against S. aureus (94% against E. coli) was achieved via a mussel-inspired approach. Subsequently, 97% S. aureus and 95% E. coli on the substrate could be released by simple ion-exchange of Br- with (CF3SO2)2N- due to the ion sensitivity of the IL molecular brushes. Thus, the proposed facile strategy towards a superior efficiency surface could be potentially used in intelligent antibacterial fields.
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Antibacterianos/farmacología , Escherichia coli/efectos de los fármacos , Imidazoles/farmacología , Líquidos Iónicos/farmacología , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/síntesis química , Antibacterianos/química , Relación Dosis-Respuesta a Droga , Imidazoles/síntesis química , Imidazoles/química , Líquidos Iónicos/síntesis química , Líquidos Iónicos/química , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Tamaño de la Partícula , Relación Estructura-Actividad , Propiedades de SuperficieRESUMEN
Applications of effective and steady metal catalysts for the hydrogen evolution reaction (HER) via electrolysis of water have a huge potential to relax energy crisis and reduce carbon dioxide emission. Herein, we design a simple, facile, and general approach for the synthesis of a series of transition-metal phosphide nanoparticles embedded in N-doped carbon (NC) nanomaterials using metal salts, abundantly available hexamethylene diamine tetra(methyl phosphonic acid), and urea as precursors. The resultant transition-metal phosphide nanoparticles can serve as high-efficiency and steady HER catalysts. Particularly, when the current density is 10 mA cm-2, the overpotentials of the obtained RhP2@NC are 30, 85, and 70 mV in acid (0.5 M H2SO4), neutral (1 M PBS), and alkaline (1 M KOH) solutions, respectively. Besides, the RhP2@NC exhibits good stability after 10 h in aforementioned solutions. More importantly, it is suited to fabricate other transition-metal phosphide nanoparticles/NC heterostructures by this synthetic strategy. The obtained CoP@NC, FeP@NC, Ni2P@NC, and Cu3P@NC also show relatively high efficiency for HER. Hence, the versatile synthesis strategy opens a new route for the research and fabrication of transition-metal phosphide-based catalysts for HER.
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Multifunctional materials, which can effectively and simultaneously remove various water-soluble contaminants like dyes and heavy metal ions, and separate oil from water, are urgent to meet increasing challenges on wastewater remediation. Herein, a cross-linked poly (acrylic acid) (PAA) modified poly (ether sulfone) nanofibrous membrane (NFM) was fabricated by a facile in-situ pre-reaction followed by electrospinning. The as-prepared NFM showed excellent hydrophilicity and underwater lipophobicity, therefore expressed excellent water permeability with high water flux (about 5142â¯Lâ¯m2â¯h-1). As a result, under solely driven by gravity, the NFM was capable to separate emulsified oil/water emulsion and a wide range of oil/water mixtures. Moreover, repeating separation tests indicated that the NFM had great long-term sustainability even after ten separation cycles. In addition, due to the introduction of PAA and the large surface-to-volume ratio, the NFM also expressed rapid adsorption capacity for cationic dyes as well as heavy metal ions; thus could simultaneously remove these contaminants during the oil/water separation process. Furthermore, the NFM could be also decorated by Ag NPs to endow the membranes with remarkable antibacterial ability against both E. coli and S. aureus. Our findings strongly suggested that the multifunctional NFM may have great potential in treating complicated wastewater.
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Increasing interests have been invested in the development of synthetic strategies toward the construction of spiro[pyrrolidine-2,3'-oxindole], which is the core structural skeleton in some compounds with diverse biological activities. In this work, an efficient diastereoselective 1,3-dipolar cycloaddition reaction of azomethine ylides generated in situ from 3-amino oxindoles and aldehydes with maleimides has been described. The protocol provides a facile and efficient access to structurally diverse succinimide-fused spiro[pyrrolidine-2,3'-oxindole] compounds in good to high yields (up to 93%) with moderate to excellent diastereoselectivities (up to >95:5). The relative stereochemistry of cycloaddition products has been assigned by X-ray diffraction analysis.