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In this study, polyoxometalates (POMs) as a core-modifying material was used to fabricate the nanofiltration (NF) membrane on the polyvinylidene fluoride (PVDF) microfiltration membrane substrate via a novel interfacial polymerization (IP) method. The formation mechanism of the POMs-modified composite membrane was proposed. The separation and antifouling properties were further investigated. After cross-linking with POMs through the new IP reaction, the modified composite membrane showed improved hydrophilicity, water flux, and salt rejection. In the humic acid fouling experiment, the POMs-modified membrane exhibited the best antifouling performance, with a flux recovery rate of up to 91.3%. Electrochemical impedance spectroscopy was further used to investigate the antifouling performance of the membranes. Nyquist and Bode plots of the POMs-modified membranes showed no significant change before and after fouling compared to the PVDF membrane substrate, indicating reduced fouling attachment on the modified membrane, which was consistent with the fouling index and flux variation observed during the fouling experiment. Our findings provide a simple and valuable route for fabricating POMs-functionalized NF membranes with desirable separation and antifouling performance.
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Aniones , Incrustaciones Biológicas , Polielectrolitos , Polivinilos , Incrustaciones Biológicas/prevención & control , Espectroscopía Dieléctrica , Polímeros de Fluorocarbono , Membranas ArtificialesRESUMEN
Hydrogen peroxide (H2O2) is considered a significant biomarker in various diseases and could induce deleterious health problems at irregular physiological concentrations. Therefore, developing a simple, efficient biocompatible nanoprobe for trace amount H2O2 detection with high sensitivity and specificity is of great help for early diagnosis and therapeutics. Herein, we designed amphiphilic poly(styrene-co-maleic anhydride) (PMSA)-encapsulated nanoclusters composed of upconversion nanoparticles (UCNPs) and manganese dioxide nanoparticles (MnO2 NPs) at a specific ratio to produce a near-infrared (NIR) excited luminescent nanoprobe for H2O2 detection. Our results revealed that the MnO2 NPs tended to experience catalytic decomposition when exposed to H2O2, while the UCNPs were retained inside the PSMA encapsulation, causing recovery of the UCNP emission band at 470 nm in accordance with H2O2 concentration. This luminescence recovery was linearly dependent on H2O2 concentrations, yielding a limit of detection (LOD) of 20 nM. The easy-to-interpret H2O2 nanoprobe also proved high selectivity in the presence of other interfering substances, and biocompatibility and water-dispersibility, making it an ideal candidate for real-time detection of disease-related H2O2 in living organisms.
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Nanopartículas , Óxidos , Peróxido de Hidrógeno , Compuestos de Manganeso , Transferencia Resonante de Energía de Fluorescencia/métodos , PolímerosRESUMEN
Surface-initiated atom transfer radical polymerization (SI-ATRP) is one of the most popular methods for surface modifications with functional polymer films, which has attracted significant attention in recent years. Herein, a facile method of gallium-based liquid metal (GLM) nanodroplets mediated SI-ATRP to prepare polymer brushes on GLM surfaces is reported. The ATRP initiator modified GLM (GLM-Br) nanodroplets act as a substrate for the in situ SI-ATRP and participate as a reducing agent to reduce Cu(II) deactivators to Cu(I) activators. UV-vis spectra confirm the feasibility of the in situ SI-ATRP and indicate that the thickness and density of polymer brushes play an important role in performing a successful ATRP on GLM nanodroplets surfaces. Homo- and block copolymers, poly(3-sulfopropyl methacrylate potassium salt) (PSPMA) and poly((2-dimethylamino)ethyl methacrylate-b-(3-sulfopropyl methacrylate potassium salt)) P(DMAEMA-b-SPMA) are successfully grafted to the GLM nanodroplets. Polymer brushes modified GLM nanodroplets show potential applications such as friction reduction and oil-water emulsion separation. GLM nanodroplets mediated SI-ATRP provides a novel and robust approach to preparing multifunctional GLM nanodroplets for different applications.
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Polímeros , Propiedades de Superficie , PolimerizacionRESUMEN
BACKGROUND: To investigate the risk factors for new vertebral compression fractures (NVCFs) after percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures (OVCFs) and to create a nomogram to predict the occurrence of new postoperative fractures. METHODS: This was a retrospective analysis of the clinical data of 529 OVCF patients who received PKP treatment in our hospital from June 2017 to June 2020. Based on whether there were new fractures within 2 years after surgery, the patients were divided into a new fracture group and a nonnew fracture group. Univariate and multivariate analyses were used to determine the risk factors for the occurrence of NVCFs after surgery. The data were randomly divided into a training set (75%) and a testing set (25%). Nomograms predicting the risk of NVCF occurrence were created based on the results of the multivariate analysis, and performance was evaluated using receiver operating characteristic curves (ROCs), calibration curves, and decision curve analyses (DCAs). A web calculator was created to give clinicians a more convenient interactive experience. RESULTS: A total of 56 patients (10.6%) had NVCFs after surgery. The univariate analysis showed significant differences in sex and the incidences of cerebrovascular disease, a positive fracture history, and bone cement intervertebral leakage between the two groups (P < 0.05). The multivariate analysis showed that sex [OR = 2.621, 95% CI (1.030-6.673), P = 0.043], cerebrovascular disease [OR = 28.522, 95% CI (8.749-92.989), P = 0.000], fracture history [OR = 12.298, 95% CI (6.250-24.199), P = 0.000], and bone cement intervertebral leakage [OR = 2.501, 95% CI (1.029-6.082), P = 0.043] were independent risk factors that were positively associated with the occurrence of NVCFs. The AUCs of the model were 0.795 (95% CI: 0.716-0.874) and 0.861 (95% CI: 0.749-0.974) in the training and testing sets, respectively, and the calibration curves showed high agreement between the predicted and actual states. The areas under the decision curve were 0.021 and 0.036, respectively. CONCLUSION: Female sex, cerebrovascular disease, fracture history and bone cement intervertebral leakage are risk factors for NVCF after PKP. Based on this, a highly accurate nomogram was developed, and a webpage calculator ( https://new-fracture.shinyapps.io/DynNomapp/ ) was created.
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Fracturas por Compresión , Cifoplastia , Fracturas de la Columna Vertebral , Anciano , Humanos , Femenino , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/epidemiología , Fracturas de la Columna Vertebral/etiología , Fracturas por Compresión/diagnóstico por imagen , Fracturas por Compresión/epidemiología , Fracturas por Compresión/etiología , Nomogramas , Cementos para Huesos/efectos adversos , Cifoplastia/efectos adversos , Estudios RetrospectivosRESUMEN
The pivotal factors affecting the survival rate of patients include metastasis and tumor recurrence after the resection of the primary tumor. Anti-PD-L1 antibody (aPD-L1) has promising efficacy but with some side effects for the off-target binding between aPD-L1 and normal tissues. Here, inspired by the excellent targeting capability of platelets with respect to tumor cells, we propose bioengineered platelets (PDNGs) with inner-loaded doxorubicin (DOX) and outer-anchored aPD-L1-cross-linked nanogels to reduce tumor relapse and metastatic spread postoperation. The cargo does not impair the normal physiological functions of platelets. Free aPD-L1 is cross-linked to form nanogels with a higher drug-loading efficiency and is sustainably released to trigger the T-cell-mediated destruction of tumor cells, reversing the tumor immunosuppressive microenvironment. PDNGs can reduce the postoperative tumor recurrence and metastasis rate, prolonging the survival time of mice. Our findings indicate that bioengineered platelets are promising in postsurgical cancer treatment by the tumor-capturing and in situ microvesicle-secreting capabilities of platelets.
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Plaquetas , Melanoma , Animales , Línea Celular Tumoral , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Humanos , Factores Inmunológicos/uso terapéutico , Inmunoterapia/métodos , Melanoma/tratamiento farmacológico , Ratones , Nanogeles , Recurrencia Local de Neoplasia , Microambiente TumoralRESUMEN
For further development and utilization of the germplasm resources of Puerariae Thomsonii Radix and Puerariae Lobatae Radix, this study developed the ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method, high performance liquid chromatography(HPLC) method, and anthrone colorimetry to detect the content of 23 flavonoids, cellulose, hemicellulose, lignin, soluble sugar, and starch in Puerariae Thomsonii Radix and Puerariae Lobatae Radix. The content differences of various chemical components were analyzed. The methodological test of the established UPLC-MS/MS method for the determination of flavonoids showed that each component had satisfactory linearity within the corresponding linear range(R~2≥0.995), and the average spiked recoveries were 94.48%-105.5%. With this method, 17 flavonoids in Puerariae Lobatae Radix and Puerariae Thomsonii Radix were detected. Based on HPLC and anthrone colorimetry, the determination methods of lignocellulose, soluble sugar, and starch were established. According to the determination results, the content of cellulose in Puerariae Thomsonii Radix was significantly lower than that in Puerariae Lobatae Radix, and the content of starch was significantly higher than that in Puerariae Lobatae Radix. The content of hemicellulose, lignin, and soluble sugar showed no significant difference between the two medicinals, and the content of soluble sugar was in highly significantly negative correlation with that of starch. The established methods are simple, rapid, accurate, and sensitive. The results can lay a basis for the evaluation, and comprehensive development and utilization of the germplasm resources of Puerariae Thomsonii Radix and Puerariae Lobatae Radix.
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Medicamentos Herbarios Chinos , Pueraria , Antracenos , Cromatografía Líquida de Alta Presión , Cromatografía Liquida , Medicamentos Herbarios Chinos/química , Flavonoides/análisis , Lignina , Pueraria/química , Almidón , Azúcares , Espectrometría de Masas en TándemRESUMEN
Drynariae Rhizoma is warm in nature and bitter in taste, mainly acting on liver and kidney systems. It is a common Chinese herbal medicine for the treatment of fracture and bone injury. The chemical compositions of Drynariae Rhizoma mainly include flavonoids, triterpenoids, phenylpropanoids and lignans. At present, modern pharmacological and clinical studies have shown that Drynariae Rhizoma has the effects of anti osteoporosis, promoting fracture healing, kidney protection, anti-inflammatory, promoting tooth growth, preventing and treating aminoglycoside ototoxicity and lowering blood lipid. In addition, the toxicity evaluation experiment of Drynariae Rhizoma has also shown that it has no obvious toxic and side effects. Naringin is a kind of dihydroflavone in Drynariae Rhizoma. Many studies have shown that naringin and other total flavonoids play an important role in anti-osteoporosis, promoting fracture healing, anti-inflammation, promoting tooth growth and lowering blood lipid. In this study, the research progresses on chemical consti-tuents and pharmacological activities of Drynariae Rhizoma in recent years were reviewed, and some mechanisms of action were summarized, to provide references for the further research and development of Drynariae Rhizoma.
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Medicamentos Herbarios Chinos , Osteoporosis , Polypodiaceae , Medicamentos Herbarios Chinos/farmacología , Flavonoides , Humanos , Osteoporosis/tratamiento farmacológico , RizomaRESUMEN
Aberrant protein phosphorylation and glycosylation are closely associated with a number of diseases. In particular, an interplay between phosphorylation and glycosylation regulates the hyperphosphorylation of protein tau, which is regarded as one of the pathologic features of Alzheimer's disease (AD). However, simultaneous characterization of these two types of post-translational modifications (PTMs) in the complex biological samples is challenging. TiO2 and the immobilized ion affinity chromatography (IMAC)-based enrichment method suffers from low selectivity and/or low recovery of phosphopeptides and glycopeptides because of the inherent limitations in intermolecular interactions. Here, we introduce a hydrogen bond-based poly[(N-isopropylacrylamide-co-4-(3-acryloylthioureido)benzoic acid0.2] (referred to as PNI-co-ATBA0.2) as a bifunctional enrichment platform to solve this bottleneck problem. Benefited from multiple hydrogen bonding interactions of ATBA with N-acetylneuraminic acid (Neu5Ac) located at the terminals of sialylated glycans and from favorable conformational transition of the copolymer chains, the smart copolymer has high adsorption capacity (370 mg·g-1) and high recovery (ranging from 74.1% ± 7.0% to 106% ± 5.0% (n = 3)) of sialylated glycopeptides. The smart copolymer also has high selectivity (79%) for simultaneous enrichment of glycopeptides and phosphopeptides from 50 µg HeLa cell lysates, yielding 721 unique phosphorylation sites from 631 phosphopeptides and 125 unique glycosylation sites from 120 glycopeptides. This study will open a new avenue and provide a novel insight for the design of enrichment materials used in PTM-proteomics.
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Glicopéptidos/análisis , Fosfopéptidos/análisis , Polímeros/química , Proteómica/métodos , Cromatografía de Afinidad , Glicosilación , Células HeLa , Humanos , Enlace de Hidrógeno , Espectrometría de Masas , Ácido N-Acetilneuramínico/química , Fosforilación , Dióxido de Silicio/química , Titanio/químicaRESUMEN
Noble metallic nanoparticles (NPs) such as gold and silver nanoparticles (AuNPs and AgNPs) have been shown to exhibit anti-tumor effect in anti-angiogenesis, photothermal and radio therapeutics. On the other hand, cell membranes are critical locales for specific targeting of cancerous cells. Therefore, NP-membrane interactions need be studied at molecular level to help better understand the underlying physicochemical mechanisms for future applications in cancer nanotechnology. Herein, we report our study on the interactions between citrate stabilized colloidal AuNPs/AgNPs (10 nm in size) and giant unilamellar vesicles (GUVs) using hyperspectral dark-field microscopy. GUVs are large model vesicle systems well established for the study of membrane dynamics. GUVs used in this study were prepared with dimyristoyl phosphatidylcholine (DMPC) and doped with cholesterol at various molar concentrations. Both imaging and spectral results support that AuNPs and AgNPs interact very differently with GUVs, i.e., AuNPs tend to integrate in between the lipid bilayer and form a uniform golden-brown crust on vesicles, whereas AgNPs are bejeweled on the vesicle surface as isolated particles or clusters with much varied configurations. The more disruptive capability of AuNPs is hypothesized to be responsible for the formation of golden brown crusts in AuNP-GUV interaction. GUVs of 20 mol% CHOL:DMPC were found to be a most economical concentration for GUVs to achieve the best integrity and the least permeability, consistent with the finding from other phase studies of lipid mixture that the liquid-ordered domains have the largest area fraction of the entire membrane at around 20 mol% of cholesterol.
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Oro/química , Nanopartículas del Metal/química , Plata/química , Liposomas Unilamelares/química , Microscopía , Tamaño de la PartículaRESUMEN
Electro-responsive smart electrorheological (ER) fluids consist of electrically polarizing organic or inorganic particles and insulating oils in general. In this study, we focus on various conducting polymers of polyaniline and its derivatives and copolymers, along with polypyrrole and poly(ionic liquid), which are adopted as smart and functional materials in ER fluids. Their ER characteristics, including viscoelastic behaviors of shear stress, yield stress, and dynamic moduli, and dielectric properties are expounded and appraised using polarizability measurement, flow curve testing, inductance-capacitance-resistance meter testing, and several rheological equations of state. Furthermore, their potential industrial applications are also covered.
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Conductividad Eléctrica , Polímeros/análisis , Polímeros/química , Reología , Algoritmos , Fenómenos Químicos , Modelos TeóricosRESUMEN
The study used use bimolecular marking methods to evaluate the lignans of Magnolia officinalis and M. officinalis var. biloba. First, we compare the chemical constituents between M. officinalis and M. officinalis var.biloba. There were significant differences in concentration of magnolignan I between leaves of these two varieties. Then we further select the p-hydroxyphenyl lignin to mining the key enzyme genes of biosynthesis from Magnolia transcriptome, and screened an encoding cinnamyl alcohol dehydrogease gene as the candidate marker of bimolecular marking methods of Magnolia quality by comparing of the expression level and structure variation in homologous gene between M. officinalis and M. officinalis var.biloba. The established method provides the technical support for bimolecular marking methods of Magnolia quality evaluation.
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Oxidorreductasas de Alcohol/genética , Magnolia/química , Proteínas de Plantas/genética , Oxidorreductasas de Alcohol/metabolismo , Lignanos/análisis , Lignanos/metabolismo , Lignina/análisis , Lignina/metabolismo , Magnolia/enzimología , Magnolia/genética , Magnolia/metabolismo , Hojas de la Planta/química , Hojas de la Planta/enzimología , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Proteínas de Plantas/metabolismo , Control de CalidadRESUMEN
The construction of N, P co-doped hierarchically porous carbons (NPHPC) by a facile and green approach is crucial for high-performance energy storage but still an enormous challenge. Herein, an environment-friendly "in-situ co-doping, self-regulation-activation" strategy is presented to one-pot synthesize NPHPC using a phytic acid-induced polyethyleneimine/chitosan gel (PEI-PA-CS) as single precursor. NPHPC displayed a specific surface area of up to 1494 m2 g-1, high specific capacitance of 449 F g-1 at 1 A g-1, outstanding rate capability and cycling durability in a wide temperature range (-20 to 60 °C). NPHPC and PEI-PA-CS electrolyte assembled symmetric quasi-solid-state flexible supercapacitor presents superb energy outputs of 27.06 Wh kg-1 at power density of 225 W kg-1. For capacitive deionization (CDI), NPHPC also exhibit an excellent salt adsorption capacity of 16.54 mg g-1 in 500 mg L-1 NaCl solution at a voltage of 1.4 V, and regeneration performance. This study provides a valuable reference for the rational design and synthesis of novel biomass-derived energy-storage materials by integrating phytic acid induced heteroatom doping and pore engineering.
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Quitosano , Capacidad Eléctrica , Quitosano/química , Porosidad , Polietileneimina/química , Carbono/química , Temperatura , AdsorciónRESUMEN
Polyacrylamide hydrogel (PAAG) is widely regarded as a safe soft tissue filler and has been extensively utilized for cosmetic enhancements, such as breast and facial augmentation in China from 1997 until its ban in 2006. Common complications associated with its use include inflammation, infection, granulomas, fibrosis, gel migration, and facial and soft tissue deformities. This case report describes a 45-year-old Chinese woman who experienced PAAG migration into her mandible 24 years after facial augmentation, causing irritation of the mandibular alveolar nerve - apparently the first documented instance of this occurrence. Surgical intervention was necessary to remove the migrated gel and associated calcifications. A literature review explored adverse events and management strategies for PAAG complications in cosmetic procedures. While generally considered safe, this report underscores the importance of meticulous injection techniques and careful anatomical site selection to prevent such severe complications.
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Homodimeric prodrug nanoassemblies (HDPNs) hold promise for improving the delivery efficiency of chemo-drugs. However, the key challenge lies in designing rational chemical linkers that can simultaneously ensure the chemical stability, self-assembly stability, and site-specific activation of prodrugs. The "in series" increase in sulfur atoms, such as trisulfide bond, can improve the assembly stability of HDPNs to a certain extent, but limits the chemical stability of prodrugs. Herein, trithiocarbonate bond (âSC(S)Sâ), with a stable "satellite-type" distribution of sulfur atoms, is developed via the insertion of a central carbon atom in trisulfide bonds. âSC(S)Sâ bond effectively addresses the existing predicament of HDPNs by improving the chemical and self-assembly stability of homodimeric prodrugs while maintaining the on-demand bioactivation. Furthermore, âSC(S)Sâ bond inhibits antioxidant defense system, leading to up-regulation of the cellular ROS and apoptosis of tumor cells. These improvements of âSC(S)Sâ bond endow the HDPNs with in vivo longevity and tumor specificity, ultimately enhancing the therapeutic outcomes. âSC(S)Sâ bond is, therefore, promising for overcoming the bottleneck of HDPNs for efficient oncological therapy.
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Antineoplásicos , Nanopartículas , Profármacos , Tionas , Profármacos/farmacología , Profármacos/química , Línea Celular Tumoral , Antineoplásicos/farmacología , Polímeros , Azufre , Nanopartículas/química , Liberación de FármacosRESUMEN
Microplastics (MPs) and Cd have been proven to inhibit methane production from anaerobic digestion of sewage sludge. However, the published studies mainly focused on their single inhibition. This cannot reflect the real-world situations where MPs and Cd co-exist. This study therefore aims to reveal the combined effect of MPs and Cd on anaerobic digestion of sewage sludge. Experimental results showed that PVC-MPs at environmentally relevant levels (e.g., 1, 10 particles/g total solids (TS)) did not affect methane yield but decrease the toxicity of Cd. When PVC-MPs were 30 particles/g TS, the cumulative methane production recovered from 58.8 % (in the presence of 5 mg Cd/g TS) to 89.7 % of the control. Organic fluxes were significantly increased compared with the control, particularly affecting the content of dissolved substances and short-chain fatty acids during anaerobic digestion. Mechanistic exploration showed that the adsorption of Cd by PVC-MPs was higher than that of sludge-substrate, which reduced the bioavailability of Cd by anaerobes, as evidenced by the increased anaerobes driven carbon flux from solid-phase to bio-methane during anaerobic digestion. Overall, these findings identified important factors in determining the toxicity of pollutants on anaerobic digestion process, providing precise data for toxicity evaluation of MPs and metals in anaerobic environment.
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Microplásticos , Aguas del Alcantarillado , Aguas del Alcantarillado/química , Cadmio/toxicidad , Plásticos , Anaerobiosis , Reactores Biológicos , MetanoRESUMEN
Intelligent hydrogel has great application potentials in flexible sensing and artificial intelligence devices due to its intrinsic characteristics. However, developing an intelligent hydrogel with favorable properties including high strength, superior toughness, excellent conductivity and ionic sensing via a facile route is still a challenge. Herein, inspired by biologically chelating interactions of phytic acid (PA) in plants, a plant-inspired versatile intelligent nanocomposite hydrogel was readily fabricated by incorporating PA into the interface of fluorescent cellulose nanocrystals (F-CNC). Under PA "molecular bridge", the hydrogel simultaneously realized superflexibility (1000 %), high strength, superb self-healing ability, remarkable fluorescence and chloride ion sensibility as well as good ionic conductivity (2.4 S/m). The hydrogel could be assembled as a flexible sensor for real-time monitoring of human motion with excellent sensitivity and stability since high sensitivity toward both strain and pressure. F-CNC acted as a functional trigger could confer the hydrogel good fluorescence and high sensitivity toward chloride ion. This design confirms the synergy of F-CNC in boosting strength, ionic sensing, and ionic conductivity, addressing a long-standing dilemma among strength, stretchability, and sensitivity for intelligent hydrogel. The one-step incorporating tactic under mild ambient conditions may open an innovative avenue for the construction of intelligent hydrogel with novel properties.
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Inteligencia Artificial , Nanopartículas , Humanos , Nanogeles , Cloruros , Celulosa , Colorantes , Conductividad Eléctrica , Halógenos , Hidrogeles , Ácido FíticoRESUMEN
In this study, we investigated the emission and fate of 9 organophosphate esters (OPEs) from a natural environment chamber, in which three environment matrices (i.e., air, dust, and window film samples) as well as three decoration materials (i.e., laminate flooring, latex paint, and nonwoven paper) were collected within gradient variation of room temperature and relative humidity. ΣAlkyl-OPEs and ΣCl-OPEs were the predominant classes in the three environment matrices, accounting - on average - for 98.7%, 99.8% and 99.3% of ΣOPEs in indoor dust, air and window film, respectively. TBOEP was the most abundant OPE in air, dust, and laminate flooring, respectively, while tris (2-chloro-isopropyl) phosphate (TCIPP) and tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) in nonwoven paper and latex paint, respectively. The results showed that higher room temperature expedited the emission of OPEs to indoor air. However, the room temperature and relative humidity had no effect on the levels of OPEs in dust. The OPEs equilibrium time in indoor environment may be dependent on room temperature and relative humidity. The area specific emission rates (SERs) of the three materials were calculated, and an optimal expression based on the concept of mass balance model was constructed, preliminarily revealing a general relationship between OPEs source and sink effects in indoor environment.
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Retardadores de Llama , China , Polvo/análisis , Monitoreo del Ambiente , Ésteres/análisis , Retardadores de Llama/análisis , Látex , Organofosfatos/análisis , FosfatosRESUMEN
Nanoparticle-anchored platelet systems hold great potential to act as drug carriers in post-surgical cancer treatment due to their intrinsic ability to target the bleeding sites. However, rational design is still needed to further improve its cargo release profiles to meet the cytosolic delivery of therapeutic proteins with intracellular targets. Herein, we developed a tumor microenvironment (TME)-responsive backpack-conjugated platelet system to enhance intracellular protein delivery, thereby significantly inhibiting tumor recurrence after surgery. Specifically, protein nanogels encapsulating GALA and Granzyme B (GrB) are conjugated on the platelet surface via an acid-sensitive benzoic-imine linker through a biorthogonal reaction (GALA-GNGs-P). Taking advantage of wound-tropism of platelets, GALA-GNGs-P could actively accumulate at the surgical trauma and release nanogels in response to acidic TME for promoting deep penetration. Following cellular uptake, the pore-forming peptide GALA helps nanogels escape from lysosome. Subsequently, high glutathione (GSH) concentration in tumor cytoplasm facilitates GrB release from NGs, leading to intense cell apoptosis. GALA-GNGs-P shows remarkable tumor-targeting capability, high cellular uptake, and outstanding lysosomal escaping ability, which can significantly inhibit tumor recurrence in mice models with incomplete tumor resection. Our findings indicate that platelets bioengineered with TME-responsive protein nanogels provide an option to intracellularly deliver therapeutic proteins for the post-surgical treatment of cancer. STATEMENT OF SIGNIFICANCE: Platelet-based drug delivery systems (DDSs) have gained considerable achievements in post-surgical cancer treatment. However, there is no research exploring their potential in realizing the controllable release of cargoes in the acidic tumor microenvironment (TME). Herein, we developed a TME-responsive bioengineered platelet delivery platform (GALA-GNGs-P) for achieving controllable and effective protein intracellular delivery to overcome post-surgical tumor recurrence. Our surface-anchored nanogel-platelet system has the following advantages: (i) improving the loading efficiency of therapeutic proteins, (ii) affecting no physiological function of platelets, (iii) realizing on-demand cargo release in the acidic TME, and (iv) helping proteins escape from endosomal entrapment. Our findings further explored the prospect of cellular backpack system and realized the controllable release of cargoes in the acidic TME.
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Neoplasias , Microambiente Tumoral , Ratones , Animales , Proteínas de la Membrana , Recurrencia Local de Neoplasia/tratamiento farmacológico , Nanogeles , Sistemas de Liberación de Medicamentos , Neoplasias/tratamiento farmacológicoRESUMEN
Rheumatoid arthritis (RA) is an inflammatory type of arthritis that causes joint pain and damage. The inflammatory cell infiltration (e.g., M1 macrophages), the poor O2 supply at the joint, and the excess reactive oxygen species (ROS)-induced oxidative injury are the main causes of RA. We herein report a polydopamine (PDA)-coated CeO2-dopped zeolitic imidazolate framework-8 (ZIF-8) nanocomposite CeO2-ZIF-8@PDA (denoted as CZP) that can synergistically treat RA. Under near-infrared (NIR) light irradiation, PDA efficiently scavenges ROS and results in an increased temperature in the inflamed area because of its good light-to-heat conversion efficiency. The rise of temperature serves to obliterate hyper-proliferative inflammatory cells accumulated in the diseased area while vastly promoting the collapse of the acidic-responsive skeleton of ZIF-8 to release the encapsulated CeO2. The released CeO2 exerts its catalase-like activity to relieve hypoxia by generating oxygen via the decomposition of H2O2 highly expressed in the inflammatory sites. Thus, the constructed CZP composite can treat RA through NIR-photothermal/ROS-scavenging/oxygen-enriched combinative therapy and show good regression of pro-inflammatory cytokines and hypoxia-inducible factor-1α (HIF-1α) in vitro and promising therapeutic effect on RA in rat models. The multimodal nano-platform reported herein is expected to shed light on the design of synergistic therapeutic nanomedicine for effective RA therapy.
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Artritis Reumatoide , Zeolitas , Animales , Artritis Reumatoide/inducido químicamente , Artritis Reumatoide/terapia , Peróxido de Hidrógeno/efectos adversos , Concentración de Iones de Hidrógeno , Indoles , Oxígeno/efectos adversos , Polímeros , Ratas , Especies Reactivas de Oxígeno/efectos adversosRESUMEN
Conductive hydrogels featuring a modulus similar to the skin have flourished in health monitoring and human-machine interface systems. However, developing conductive hydrogels with self-healing and tunable force-electrical performance remains a problem. Herein, a hydrogen bonding cross-linking strategy was utilized by incorporating silk sericin-modified carbon nanotubes (SS@CNTs) into sodium alginate (SA) and polyvinyl alcohol (PVA). Hydrogels synthesized with desirable tensile strength and self-healing ability (67.2 % self-healing efficiency in fracture strength) assembled into strain sensors with a low detection limit of 0.5 % and a gauge factor (GF) of 4.75 (0-17 %). Additionally, as-prepared hydrogels exhibit high sensitivity to tiny pressure changes, allowing recognition of complex handwriting. Notably, resulting hydrogels possess self-powered property, generating up to 215 V and illuminating 100 commercial green LEDs. This work stems from the pressing need for multifunctional hydrogels with prospective applications in human motion sensing and energy harvesting.