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Electrocaloric1,2 and electrostrictive3,4 effects concurrently exist in dielectric materials. Combining these two effects could achieve the lightweight, compact localized thermal management that is promised by electrocaloric refrigeration5. Despite a handful of numerical models and schematic presentations6,7, current electrocaloric refrigerators still rely on external accessories to drive the working bodies8-10 and hence result in a low device-level cooling power density and coefficient of performance (COP). Here we report an electrocaloric thin-film device that uses the electro-thermomechanical synergy provided by polymeric ferroelectrics. Under one-time a.c. electric stimulation, the device is thermally and mechanically cycled by the working body itself, resulting in an external-driver-free, self-cycling, soft refrigerator. The prototype offers a directly measured cooling power density of 6.5 W g-1 and a peak COP exceeding 58 under a zero temperature span. Being merely a 30-µm-thick polymer film, the device achieved a COP close to 24 under a 4 K temperature span in an open ambient environment (32% thermodynamic efficiency). Compared with passive cooling, the thin-film refrigerator could immediately induce an additional 17.5 K temperature drop against an electronic chip. The soft, polymeric refrigerator can sense, actuate and pump heat to provide automatic localized thermal management.
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Polímeros , Refrigeración , Termodinámica , Refrigeración/instrumentación , Polímeros/química , Frío , Electricidad , Diseño de Equipo , Estimulación Eléctrica , TemperaturaRESUMEN
Micro- and nanoplastics (MNPs) are attracting increasing attention due to their persistence and potential ecological risks. This review critically summarizes the effects of photo-oxidation on the physical, chemical, and biological behaviors of MNPs in aquatic and terrestrial environments. The core of this paper explores how photo-oxidation-induced surface property changes in MNPs affect their adsorption toward contaminants, the stability and mobility of MNPs in water and porous media, as well as the transport of pollutants such as organic pollutants (OPs) and heavy metals (HMs). It then reviews the photochemical processes of MNPs with coexisting constituents, highlighting critical factors affecting the photo-oxidation of MNPs, and the contribution of MNPs to the phototransformation of other contaminants. The distinct biological effects and mechanism of aged MNPs are pointed out, in terms of the toxicity to aquatic organisms, biofilm formation, planktonic microbial growth, and soil and sediment microbial community and function. Furthermore, the research gaps and perspectives are put forward, regarding the underlying interaction mechanisms of MNPs with coexisting natural constituents and pollutants under photo-oxidation conditions, the combined effects of photo-oxidation and natural constituents on the fate of MNPs, and the microbiological effect of photoaged MNPs, especially the biotransformation of pollutants.
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Contaminantes Ambientales , Microbiota , Contaminantes Químicos del Agua , Microplásticos , Adsorción , Oxidación-Reducción , PlásticosRESUMEN
Human beings have a greater need to pursue life and manage personal or family health in the context of the rapid growth of artificial intelligence, big data, the Internet of Things, and 5G/6G technologies. The application of micro biosensing devices is crucial in connecting technology and personalized medicine. Here, the progress and current status from biocompatible inorganic materials to organic materials and composites are reviewed and the material-to-device processing is described. Next, the operating principles of pressure, chemical, optical, and temperature sensors are dissected and the application of these flexible biosensors in wearable/implantable devices is discussed. Different biosensing systems acting in vivo and in vitro, including signal communication and energy supply are then illustrated. The potential of in-sensor computing for applications in sensing systems is also discussed. Finally, some essential needs for commercial translation are highlighted and future opportunities for flexible biosensors are considered.
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Técnicas Biosensibles , Dispositivos Electrónicos Vestibles , Humanos , Materiales Biocompatibles , Inteligencia Artificial , Prótesis e ImplantesRESUMEN
The level of microplastics (MPs) in wastewater treatment plants (WWTPs) has been well evaluated by the particle number, while the mass concentration of MPs and especially nanoplastics (NPs) remains unclear. In this study, pyrolysis gas chromatography-mass spectrometry was used to determine the mass concentrations of MPs and NPs with different size ranges (0.01-1, 1-50, and 50-1000 µm) across the whole treatment schemes in two WWTPs. The mass concentrations of total MPs and NPs decreased from 26.23 and 11.28 µg/L in the influent to 1.75 and 0.71 µg/L in the effluent, with removal rates of 93.3 and 93.7% in plants A and B, respectively. The proportions of NPs (0.01-1 µm) were 12.0-17.9 and 5.6-19.5% in plants A and B, respectively, and the removal efficiency of NPs was lower than that of MPs (>1 µm). Based on annual wastewater effluent discharge, it is estimated that about 0.321 and 0.052 tons of MPs and NPs were released into the river each year. Overall, this study investigated the mass concentration of MPs and NPs with a wide size range of 0.01-1000 µm in wastewater, which provided valuable information regarding the pollution level and distribution characteristics of MPs, especially NPs, in WWTPs.
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Microplásticos , Contaminantes Químicos del Agua , Aguas Residuales , Plásticos/análisis , Cromatografía de Gases y Espectrometría de Masas , Pirólisis , Contaminantes Químicos del Agua/análisis , Eliminación de Residuos Líquidos , Monitoreo del Ambiente/métodosRESUMEN
The intertidal sediment environment is dynamic and the biofilm bacterial community within it must constantly adapt, but an understanding of the differences in the biofilm bacterial community within sediments of different types is still relatively limited. The semi-enclosed Jiaozhou Bay has a temperate monsoon climate, with strong currents at the mouth of the bay. In this study, the structure of the bacterial community in Jiaozhou Bay sediment biofilms are described using high-throughput 16 S rRNA gene sequencing and the effects of temporal change and different sediment environment types are discussed. Alpha diversity was significantly higher in sandy samples than in muddy samples. Sandy sediments with increased heterogeneity promote bacterial aggregation. Beta diversity analysis showed significant differences between sediment types and between stations. Proteobacteria and Acidobacteria were significantly more abundant at ZQ, while Campilobacterota was significantly more abundant at LC. The relative abundances of Bacteroidetes, Campilobacterota, Firmicutes, and Chloroflexi were significantly higher in the muddy samples, while Actinobacteria and Proteobacteria were higher in the sandy samples. There were different phylum-level biomarkers between sediment types at different stations. There were also different patterns of functional enrichment in biogeochemical cycles between sediment types and stations with the former having more gene families that differed significantly, highlighting their greater role in determining bacterial function. Bacterial amplicon sequence variant variation between months was less than KEGG ortholog variation between months, presumably the temporal change had an impact on shaping the intertidal sediment bacterial community, although this was less clear at the gene family level. Random forest prediction yielded a combination of 43 family-level features that responded well to temporal change, reflecting the influence of temporal change on sediment biofilm bacteria.
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OBJECTIVES: To assess the efficacy of topical sialogogue spray containing malic acid 1% for treating xerostomia. METHODS: We searched PubMed, Cochrane Library, Embase, ClinicalTrials.gov and Web of Science databases. Literature search, screening, study selection, data collection, data extraction and assessment of bias risk were independently conducted by two reviewers. The study appraisal was performed by Cochrane Collaboration's tool for assessing bias risk. The systematic review registration number was PROSPERO-CRD42021241322. All statistical analyses were performed using Review Manager version 5.4. RESULTS: Five original articles involving 244 patients with xerostomia who received topical sialogogue spray (malic acid 1%) or placebo for two weeks were included in this review. Based on the questionnaire survey, the topical sialogogue spray (malic acid 1%) improved the symptoms of dry mouth significantly better than the placebo, which was reflected in the Dry Mouth Questionnaire (DMQ), Xerostomia Inventory (XI) and Visual Analogue Scale (VAS) scores. Regarding the increase in unstimulated and stimulated saliva flow rates, the intervention group was also better than the placebo group after a two-week course of treatment. CONCLUSIONS: Although the included studies are limited, our results show that topical sialogogue spray (malic acid 1%) is an effective method for the treatment of xerostomia. Additional randomised controlled trials in the future are needed to provide high-quality evidence of this therapy and to improve clinical practice guidelines.
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Xerostomía , Humanos , Xerostomía/tratamiento farmacológico , Malatos/efectos adversos , Encuestas y CuestionariosRESUMEN
Metal film-based stretchable strain sensors hold great promise for applications in various domains, which require superior sensitivity-stretchability-cyclic stability synergy. However, the sensitivity-stretchability trade-off has been a long-standing dilemma and the metal film-based strain sensors usually suffer from weak cyclic durability, both of which significantly limit their practical applications. Here, we propose an extremely facile, low-cost and spontaneous strategy that incorporates topological gradients in metal film-based strain sensors, composed of intrinsic (grain size and interface) and extrinsic (film thickness and wrinkle) microstructures. The topological gradient strain sensor exhibits an ultrawide stretchability of 100% while simultaneously maintaining a high sensitivity at an optimal topological gradient of 4.5, due to the topological gradients-induced multistage film cracking. Additionally, it possesses a decent cyclic stability for >10â¯000 cycles between 0 and 40% strain enabled by the gradient-mixed metal/elastomer interfaces. It can monitor the full-range human activities from subtle pulse signals to vigorous joint movements.
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Dispositivos Electrónicos Vestibles , Elastómeros/química , Humanos , Metales , Monitoreo FisiológicoRESUMEN
The conversion of lignocellulosic biomass to second-generation biofuels through enzymes is achieved at a high cost. Filamentous fungi through a combination of oxidative enzymes can easily disintegrate the glycosidic bonds of cellulose. The combination of cellobiose dehydrogenase (CDH) with lytic polysaccharide monooxygenases (LPMOs) enhances cellulose degradation in many folds. CDH increases cellulose deconstruction via coupling the oxidation of cellobiose to the reductive activation of LPMOs by catalyzing the addition of oxygen to C-H bonds of the glycosidic linkages. Fungal LPMOs show different regio-selectivity (C1 or C4) and result in oxidized products through modifications at reducing as well as nonreducing ends of the respective glucan chain. T. reesei LPMOs have shown great potential for oxidative cleavage of cellobiose at C1 and C4 glucan bonds, therefore, the incorporation of heterologous CDH further increases its potential for biofuel production for industrial purposes at a reduced cost. We introduced CDH of Phanerochaete chrysosporium (PcCDH) in Trichoderma reesei (which originally lacked CDH). We purified CDH through affinity chromatography and analyzed its enzymatic activity, electron-donating ability to LPMO, and the synergistic effect of LPMO and CDH on cellulose deconstruction. The optimum temperature of the recombinant PcCDH was found to be 45 °C and the optimum pH of PcCDH was observed as 4.5. PcCDH has high cello-oligosaccharide kcat, Km, and kcat/Km values. The synergistic effect of LPMO and cellulase significantly improved the degradation efficiency of phosphoric acid swollen cellulose (PASC) when CDH was used as the electron donor. We also found that LPMO undergoes auto-oxidative inactivation, and when PcCDH is used an electron donor has the function of a C1-type LPMO electron donor without additional substrate increments. This work provides novel insights into finding stable electron donors for LPMOs and paves the way forward in discovering efficient CDHs for enhanced cellulose degradation.
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Celobiosa , Oxigenasas de Función Mixta , Oxigenasas de Función Mixta/metabolismo , Electrones , Polisacáridos/metabolismo , Celulosa/metabolismoRESUMEN
The lytic polysaccharide monooxygenase (LPMO) in the auxiliary active protein family (AA family) catalyzes the oxidative depolymerization of various refractory carbohydrates including cellulose, chitin and starch. While accumulating studies investigate the enzymology of LPMO, the research on the inactivation of LPMO genes has been rarely explored. In this study, five LPMO genes PaLPMO11A (Pa_4_4790), PaLPMO11B (Pa_1_5310), PaLPMO11C (Pa_2_7840), PaLPMO11D (Pa_2_8610) and PaLPMO11E (Pa_3_9420) of the AA11 family in the filamentous fungus Podospora anserina were knocked out by homologous recombination. Single mutants ΔPaLPMO11A (ΔA), ΔPaLPMO11B (ΔB), ΔPaLPMO11C (ΔC), ΔPaLPMO11D (ΔD) and ΔPaLPMO11E (ΔE) were constructed, and then all polygenic mutants were constructed via genetic crosses. The differences in the growth rate and sexual reproduction between wild type and mutant strains were observed on different carbon source media. The alteration of oxidative stress and cellulose degradation ability were found on DAB and NBT staining and cellulase activity determination. These results implicated that LPMO11 genes play a key role in the growth, development, and lignocellulose degradation of P. anserina. The results showed that the spore germination efficiency, growth rate and reproductive capacity of mutant strains including ΔBΔCΔE, ΔAΔBΔCΔE, ΔAΔCΔDΔE and ΔAΔBΔCΔDΔE was significantly decreased on different cellulose carbon sources and the remaining strains have no difference. The reduced utilization of various carbon sources, the growth rate, the spore germination rate, the number of fruiting bodies, the normal fruiting bodies, the shortened life span and the ability to degrade cellulose were found in strains which all five genes in the PaLPMO11 family were deleted. However, the strain still had 45% cellulase activity compared to wild type. These results suggest that LPMO11 genes may be involved in the growth and development, sexual reproduction, senescence and cellulose degradation of P. anserina. This study provides information for systematically elucidating the regulatory mechanism of lignocellulose degradation in filamentous fungus P. anserina.
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Proteínas Fúngicas , Oxigenasas de Función Mixta , Podospora , Podospora/genética , Podospora/enzimología , Podospora/metabolismo , Podospora/crecimiento & desarrollo , Oxigenasas de Función Mixta/genética , Oxigenasas de Función Mixta/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Celulosa/metabolismo , Polisacáridos/metabolismo , Estrés OxidativoRESUMEN
Nanoplastics (NPs) are currently considered an environmental pollutant of concern, but the actual extent of NP pollution in environmental water bodies remains unclear and there is not enough quantitative data to conduct proper risk assessments. In this study, a pretreatment method combining ultrafiltration (UF, 100 kDa) with hydrogen peroxide digestion and subsequent detection with pyrolysis gas chromatography-mass spectrometry (Py-GC/MS) was developed and used to identify and quantify six selected NPs in surface water (SW) and groundwater (GW), including poly(vinylchloride) (PVC), poly(methyl methacrylate) (PMMA), polypropylene (PP), polystyrene (PS), polyethylene (PE), and poly(ethylene terephthalate) (PET). The results show that the proposed method could detect NPs in environmental water samples. Nearly all selected NPs could be detected in the surface water at all locations, while PVC, PMMA, PS, and PET NPs were frequently below the detection limit in the groundwater. PP (32.9-69.9%) and PE (21.3-44.3%) NPs were the dominant components in both surface water and groundwater, although there were significant differences in the pollution levels attributed to the filtration efficiency of riverbank, with total mass concentrations of 0.283-0.793 µg/L (SW) and 0.021-0.203 µg/L (GW). Overall, this study quantified the NPs in complex aquatic environments for the first time, filling in gaps in our knowledge about NP pollution levels and providing a useful methodology and important reference data for future research.
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Agua Subterránea , Contaminantes Químicos del Agua , Cromatografía de Gases y Espectrometría de Masas , Microplásticos , Plásticos/análisis , Polietileno/análisis , Polimetil Metacrilato/análisis , Polipropilenos/análisis , Poliestirenos , Cloruro de Polivinilo , Pirólisis , Agua , Contaminantes Químicos del Agua/químicaRESUMEN
This work suggested that Cu2+ ion coordinated by the peptide with a histidine (His or H) residue in the first position from the free N-terminal reveals oxidase-mimicking activity. A biotinylated polymer was prepared by modifying His residues on the side chain amino groups of lysine residues (denoted as KH) to chelate multiple Cu2+ ions. The resulting biotin-poly-(KH-Cu)20 polymer with multiple catalytic sites was employed as the signal label for immunoassay. Prostate specific antigen (PSA) was determined as the model target. The captured biotin-poly-(KH-Cu)20 polymer could catalyze the oxidation of o-phenylenediamine (OPD) to produce fluorescent 2,3-diaminophenazine (OPDox). The signal was proportional to PSA concentration from 0.01 to 2 ng/mL, and the detection limit was found to be eight pg/mL. The high sensitivity of the method enabled the assays of PSA in real serum samples. The work should be valuable for the design of novel biosensors for clinical diagnosis.
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Cobre , Antígeno Prostático Específico , Biotina , Cobre/química , Humanos , Inmunoensayo/métodos , Masculino , Fenilendiaminas , PolímerosRESUMEN
Polyethyleneimine (PEI) has a good spongy proton effect and is an excellent nonviral gene vector, but its high charge density leads to the instability and toxicity of PEI/DNA complexes. Cell membrane (CM) capsules provide a universal and natural solution for this problem. Here, CM-coated PEI/DNA capsules (CPDcs) were prepared through extrusion, and the extracellular matrix was coated on CPDcs (ECM-CPDcs) for improved targeting. The results showed that compared with PEI/DNA complexes, CPDcs had core-shell structures (PEI/DNA complexes were coated by a 6-10 nm layer), lower cytotoxicity, and obvious homologous targeting. The internalization and transfection efficiency of 293T-CM-coated PEI70k/DNA capsules (293T-CP70Dcs) were 91.8 and 74.5%, respectively, which were higher than those of PEI70k/DNA complexes. Then, the internalization and transfection efficiency of 293T-CP70Dcs were further improved by ECM coating, which were 94.7 and 78.9%, respectively. Then, the internalization and transfection efficiency of 293T-CP70Dcs were further improved by ECM coating, which were 94.7 and 78.9%, respectively. Moreover, the homologous targeting of various CPDcs was improved by ECM coating, and other CPDcs also showed similar effects as 293T-CP70Dcs after ECM coating. These findings suggest that tumor-targeted CPDcs may have considerable advantages in gene delivery.
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Membrana Celular/química , ADN/administración & dosificación , Matriz Extracelular/química , Técnicas de Transferencia de Gen/estadística & datos numéricos , Terapia Genética , Neoplasias/terapia , Polietileneimina/química , Proliferación Celular , ADN/química , ADN/genética , Células HeLa , Células Hep G2 , Humanos , Técnicas In Vitro , Neoplasias/genética , Neoplasias/patologíaRESUMEN
BACKGROUND: Autophagy is a conserved catabolic process, which plays an important role in regulating tumor cell motility and degrading protein aggregates. Chemotherapy-induced autophagy may lead to tumor distant metastasis and even chemo-insensitivity in the therapy of hepatocellular carcinoma (HCC). Therefore, a vast majority of HCC cases do not produce a significant response to monotherapy with autophagy inhibitors. RESULTS: In this work, we developed a biomimetic nanoformulation (TH-NP) co-encapsulating Oxaliplatin (OXA)/hydroxychloroquine (HCQ, an autophagy inhibitor) to execute targeted autophagy inhibition, reduce tumor cell migration and invasion in vitro and attenuate metastasis in vivo. The tumor cell-specific ligand TRAIL was bioengineered to be stably expressed on HUVECs and the resultant membrane vesicles were wrapped on OXA/HCQ-loaded PLGA nanocores. Especially, TH-NPs could significantly improve OXA and HCQ effective concentration by approximately 21 and 13 times in tumor tissues compared to the free mixture of HCQ/OXA. Moreover, the tumor-targeting TH-NPs released HCQ alkalized the acidic lysosomes and inhibited the fusion of autophagosomes and lysosomes, leading to effective blockade of autophagic flux. In short, the system largely improved chemotherapeutic performance of OXA on subcutaneous and orthotopic HCC mice models. Importantly, TH-NPs also exhibited the most effective inhibition of tumor metastasis in orthotopic HCCLM3 models, and in the HepG2, Huh-7 or HCCLM3 metastatic mice models. Finally, we illustrated the enhanced metastasis inhibition was attributed to the blockade or reverse of the autophagy-mediated degradation of focal adhesions (FAs) including E-cadherin and paxillin. CONCLUSIONS: TH-NPs can perform an enhanced chemotherapy and antimetastatic effect, and may represent a promising strategy for HCC therapy in clinics.
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Antineoplásicos/farmacología , Autofagia/efectos de los fármacos , Materiales Biomiméticos/química , Nanopartículas/química , Animales , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/uso terapéutico , Cadherinas/metabolismo , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Portadores de Fármacos/química , Liberación de Fármacos , Adhesiones Focales/química , Adhesiones Focales/efectos de los fármacos , Adhesiones Focales/metabolismo , Humanos , Hidroxicloroquina/química , Hidroxicloroquina/metabolismo , Hidroxicloroquina/farmacología , Hidroxicloroquina/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Ratones , Neoplasias/patología , Oxaliplatino/química , Oxaliplatino/metabolismo , Oxaliplatino/farmacología , Oxaliplatino/uso terapéutico , Paxillin/metabolismo , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/químicaRESUMEN
OBJECTIVE: To study the effect of the application timing of vasoactive agents on the prognosis of children in the third stage of hand-foot-mouth disease (HFMD). METHODS: A retrospective analysis was performed on the medical data of children in the third stage of HFMD between April 2012 and September 2016. According to the application time of vasoactive agents (milrinone combined with phentolamine) after admission, the children were divided into an early stage (within 2 hours after admission) group with 32 children, a middle stage (within 2-6 hours after admission) group with 28 children, and a late stage (more than 6 hours after admission) group with 26 children. Venous blood samples were collected before vasoactive agent treatment and after 24 hours of vasoactive agent treatment to measure the levels of creatine kinase-MB (CK-MB), troponin (TnI), and brain natriuretic peptide (BNP). The recovery time of left ventricular ejection fraction (LVEF), respiratory rate, blood pressure, and heart rate were recorded. The response rate to the treatment within 72 hours of treatment was evaluated. RESULTS: The early stage group had a significantly higher overall response rate to the treatment than the middle stage and late stage groups (P<0.0167). After 24 hours of treatment, there were significant differences in heart rate, blood pressure, respiratory rate, and LVEF among the three groups (P<0.05). The early stage group showed the most significant improvement in these parameters (P<0.0167). Compared with the middle stage and late stage groups, the early stage group had significantly shorter recovery time of LVEF, respiratory rate, heart rate, and blood pressure (P<0.0167). After 24 hours of treatment, the early stage group had a significantly lower level of BNP than the middle stage and late stage groups (P<0.05). CONCLUSIONS: Vasoactive agents should be given to children with critical HFMD as early as possible to improve cardiovascular function, reduce the risk of disease progression, and improve prognosis.
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Enfermedad de Boca, Mano y Pie , Niño , Enfermedad de Boca, Mano y Pie/tratamiento farmacológico , Humanos , Pronóstico , Estudios Retrospectivos , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
Although photothermal therapy (PTT) is preclinically applied in solid tumor treatment, incomplete tumor removal of PTT and heat endurance of tumor cells induces significant tumor relapse after treatment, therefore lowering the therapeutic efficiency of PTT. Herein, a programmable therapeutic strategy that integrates photothermal therapeutic agents (PTAs), DNAzymes, and artificial engineered natural killer (A-NK) cells for immunotherapy of hepatocellular carcinoma (HCC) is designed. The novel PTAs, termed as Mn-CONASHs, with 2D structure are synthesized by the coordination of tetrahydroxyanthraquinone and Mn2+ ions. By further adsorbing polyetherimide/DNAzymes on the surface, the DNAzymes@Mn-CONASHs exhibit excellent light-to-heat conversion ability, tumor microenvironment enhanced T1 -MRI guiding ability, and antiheat endurance ability. Furthermore, the artificial engineered NK cells with HCC specific targeting TLS11a-aptamer decoration are constructed for specifically eliminating any possible residual tumor cells after PTT, to systematically enhance the therapeutic efficacy of PTT and avoid tumor relapse. Taken together, the potential of A-NK cells combined with antiheat endurance as a powerful strategy for immuno-enhancing photothermal therapy efficiency of solid tumors is highlighted, and the current strategy might provide promising prospects for cancer therapy.
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Células Artificiales , Carcinoma Hepatocelular/terapia , Ingeniería Celular , Hipertermia Inducida , Inmunoterapia , Células Asesinas Naturales/inmunología , Neoplasias Hepáticas/terapia , Fototerapia , Carcinoma Hepatocelular/diagnóstico por imagen , ADN Catalítico/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Neoplasias Hepáticas/diagnóstico por imagen , Imagen por Resonancia Magnética , Manganeso/química , Nanopartículas/ultraestructura , Espectrometría de Fluorescencia , Microambiente TumoralRESUMEN
Polymeric prodrug based on therapeutic nanomedicine has demonstrated great promise for effective tumor growth inhibition, however, the drawbacks of low drug-loading and weak micellar stability limit its application for clinical cancer therapy. Herein, a reduction-responsive starburst block copolymer prodrug CCP [ß-cyclodextrin (ß-CD)-PCPTXX-POEGMA, XX: SS or CC] has been developed for cancer therapy. And CCP is composed of ß-CD-Br core with multiple reactive sites, as well as a diblock copolymer containing hydrophobic polymerized camptothecin (PCPT) prodrug chain and hydrophilic poly[(ethylene glycol) methyl ether methacrylate] (OEGMA) chain. A family of CCP polymeric prodrugs with different drug loading contents (up to 25%) and various sizes of unimolecular micelles (UMs) (around 30 nm) were obtained by adjusting the block ratio of PCPTXX and POEGMA. On account of the amphiphilic structure feature, CPP could take shape water-soluble UMs in aqueous medium with excellent micellar stability. Under imitatively reductive tumor microenvironment, anticancer drug CPT could rapidly escape from CCP UMs in terms of disulfide bond breakage. However, this behavior is strongly refrained in the physiological environment. In vitro and in vivo outcome confirmed that CCP UMs showed excellent performance of sufficient tumor accumulation, high-efficiency tumor growth inhibition and low-toxicity for healthy tissues. Based on these gratifying therapeutic efficacy, it is believed that as-present starburst prodrug strategy can offer a brand-new insight for high-efficiency therapeutic nanoplatforms for chemotherapy application.
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Antineoplásicos/administración & dosificación , Sistemas de Liberación de Medicamentos , Micelas , Polímeros/química , Profármacos/química , Animales , Antineoplásicos/química , Camptotecina/administración & dosificación , Camptotecina/química , Femenino , Células HeLa , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Células MCF-7 , Ratones Endogámicos BALB C , Ratones Desnudos , Microambiente Tumoral , beta-Ciclodextrinas/químicaRESUMEN
BACKGROUND The aim of this study was to investigate changes in event-related potentials (ERPs) between coma and awakening in patients with large left hemispheric infarction (left LHI). MATERIAL AND METHODS Ten patients with left LHI who suffered coma and survived to awaken were enrolled in this study. The eye-opening subscore of the Glasgow Coma Scale (GCS) was used to assess the extent of patients' arousal. ERPs elicited by the passive oddball paradigm were collected during coma and awakening states, respectively. Peak latencies, peak amplitudes, topography, and time-frequency information of P1, N1, P2, and mismatch negativity (MMN) were compared between the 2 sessions. RESULTS No significant differences in the peak amplitudes and peak latencies of P1 and N1, but significantly greater P2 amplitude with shorter latency in left hemisphere and midline was shown in the awakening state compared with that in coma. A marked shift of P2 topography in response to deviant tones was also seen, from the right centro-parieto-frontal areas during coma to left frontal-midline areas during awakening. MMN waveforms were not detected in 6/10 patients during the coma state, but these 6 patients all recovered to awakening. Evoked oscillations in bilateral hemisphere were profoundly inhibited during the coma state, with poor inter-trial phase synchronization, while obvious activities with broader frequency ranges and consistent inter-trial phase synchronization were observed during awakening state, and different frequency activities were distributed in distinct brain regions. CONCLUSIONS P2 may be a central index of coma recovery and a component of the arousal system. Changes in time-frequency information could provide more information during coma recovery, perhaps including some cognitive processing of the sensory stimulus.
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Infarto Cerebral/fisiopatología , Coma/fisiopatología , Potenciales Evocados/fisiología , Estimulación Acústica/métodos , Anciano , Percepción Auditiva/fisiología , Encéfalo/fisiología , Mentón , Estado de Conciencia/fisiología , Electroencefalografía/métodos , Potenciales Evocados Auditivos/fisiología , Femenino , Escala de Coma de Glasgow , Humanos , Masculino , Pacientes , Tiempo de ReacciónRESUMEN
Water-soluble carbohydrates in raw lignocellulosic biomass are converted into hydroxymethylfurfural (HMF) in the acid-based pretreatment, thus increasing the detoxification intensity and reducing the fermentation efficiency of cellulosic ethanol. Therefore, reducing water-soluble carbohydrates in raw corn stover is crucially important to reduce the inhibitors' generation and improve the ethanol fermentation efficiency. In this study, aerobic solid-state fermentation of corn stover by inoculating Aspergillus niger spores converted 83% of the endogenous water-soluble carbohydrates into citric acid, leading to the decrease of 41% of HMF generation and 8% of sulfuric acid usage during the dry acid pretreatment. The reduced inhibitor generation improved the ethanol fermentability by 11% more ethanol than that of the corn stover without water-soluble carbohydrates' removal. This suggests that the removal of the water-soluble carbohydrates before pretreatment significantly reduced the inhibitors' generation in pretreatment and improved the fermentation efficiency of cellulosic ethanol.
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Aspergillus niger/crecimiento & desarrollo , Biomasa , Ácido Cítrico/farmacología , Etanol/metabolismo , Lignina/química , Zea mays/química , Ácido Cítrico/química , Furaldehído/análogos & derivados , Furaldehído/química , Furaldehído/farmacología , Solubilidad , Agua/químicaRESUMEN
Coagulation is the best available method for removing intracellular organic matter (IOM), which is released from algae cells and is an important precursor to disinfection by-products in drinking water treatment. To gain insight into the best strategy to optimize IOM removal, the coagulation performance of two Al salts, i.e., aluminum chloride (AlCl3) and polyaluminum chloride (PACl, containing 81.2% Al13), was investigated to illuminate the effect of Al species distribution on IOM removal. PACl showed better removal efficiency than AlCl3 with regard to the removal of turbidity and dissolved organic carbon (DOC), owing to the higher charge neutralization effect and greater stability of pre-formed Al13 species. High pressure size exclusion chromatography analysis indicated that the superiority of PACl in DOC removal could be ascribed to the higher binding affinity between Al13 polymer and the low and medium molecular weight (MW) fractions of IOM. The results of differential log-transformed absorbance at 254 and 350â¯nm indicated more significant formation of complexes between AlCl3 and IOM, which benefits the removal of tryptophan-like proteins thereafter. Additionally, PACl showed more significant superiority compared to AlCl3 in the removal of <5â¯kDa and hydrophilic fractions, which are widely viewed as the most difficult to remove by coagulation. This study provides insight into the interactions between Al species and IOM, and advances the optimization of coagulation for the removal of IOM in eutrophic water.
Asunto(s)
Aluminio/química , Espacio Intracelular/química , Compuestos Orgánicos/química , Compuestos Orgánicos/aislamiento & purificación , Polímeros/química , Eutrofización , Microcystis/citología , Microcystis/crecimiento & desarrollo , Peso MolecularRESUMEN
Despite the well-recognized merits of simultaneous saccharification and co-fermentation (SSCF) on relieving sugar product inhibition on cellulase activity, a practical concomitance difficulty of xylose with inhibitors in the pretreated lignocellulose feedstock prohibits the essential application of SSCF for cellulosic ethanol fermentation. To maximize the SSCF potentials for cellulosic ethanol production, a dry biorefining approach was proposed starting from dry acid pretreatment, disk milling, and biodetoxification of lignocellulose feedstock. The successful SSCF of the inhibitor free and xylose conserved lignocellulose feedstock after dry biorefining reached a record high ethanol titer at moderate cellulase usage and minimum wastewater generation. For wheat straw, 101.4 g/L of ethanol (equivalent to 12.8% in volumetric percentage) was produced with the overall yield of 74.8% from cellulose and xylose, in which the xylose conversion was 73.9%, at the moderate cellulase usage of 15 mg protein per gram cellulose. For corn stover, 85.1 g/L of ethanol (equivalent to 10.8% in volumetric percentage) is produced with the overall conversion of 84.7% from cellulose and xylose, in which the xylose conversion was 87.7%, at the minimum cellulase usage of 10 mg protein per gram cellulose. Most significantly, the SSCF operation achieved the high conversion efficiency by generating the minimum amount of wastewater. Both the fermentation efficiency and the wastewater generation in the current dry biorefining for cellulosic ethanol production are very close to that of corn ethanol production, indicating that the technical gap between cellulosic ethanol and corn ethanol has been gradually filled by the advancing biorefining technology.