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Nonconventional luminophores have received increasing attention, owing to their fundamental importance, advantages in outstanding biocompatibility, easy preparation, environmental friendliness, and potential applications in sensing, imaging, and encryption. Purely organic molecules with outstanding fluorescence and room-temperature phosphorescence (RTP) have emerged as a new library of benign afterglow agents. However, the cost, toxicity, high reactivity, and poor stability of materials also limit their practical applications. Therefore, some natural products, synthetic compounds, and biomolecules have entered horizons of people. The as-designed exhibits sky blue and green fluorescence emission and green RTP emission (a lifetime of 343 ms and phosphorescence quantum of 15.3%) under air condition. This study presents an organic fluorescence for biological imaging and RTP for anti-counterfeiting and encryption based on amino acids, maleic anhydride and 4-vinylbenzenesulfonic acid sodium salt hydrate. This study provides a strategy for nonconventional luminophores in designing and synthesizing pure organic RTP materials.
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Aminoácidos , Polímeros , Solubilidad , Temperatura , Agua , Aminoácidos/química , Polímeros/química , Polímeros/síntesis química , Agua/química , Luminiscencia , Estructura Molecular , Sustancias Luminiscentes/química , Sustancias Luminiscentes/síntesis química , Mediciones LuminiscentesRESUMEN
Converting spent lithium-ion batteries (LIBs) cathode materials into environmental catalysts has drawn more and more attention. Herein, we fabricated a Co3O4-based catalyst from spent LiCoO2 LIBs (Co3O4-LIBs) and found that the role of Al and Cu from current collectors on its performance is nonnegligible. The density functional theory calculations confirmed that the doping of Al and/or Cu upshifts the d-band center of Co. A Fenton-like reaction based on peroxymonosulfate (PMS) activation was adopted to evaluate its activity. Interestingly, Al doping strengthened chemisorption for PMS (from -2.615â eV to -2.623â eV) and shortened Co-O bond length (from 2.540â Å to 2.344â Å) between them, whereas Cu doping reduced interfacial charge-transfer resistance (from 28.347â kΩ to 6.689â kΩ) excepting for the enhancement of the above characteristics. As expected, the degradation activity toward bisphenol A of Co3O4-LIBs (0.523â min-1) was superior to that of Co3O4 prepared from commercial CoC2O4 (0.287â min-1). Simultaneously, the reasons for improved activity were further verified by comparing activity with catalysts doped Al and/or Cu into Co3O4. This work reveals the role of elements from current collectors on the performance of functional materials from spent LIBs, which is beneficial to the sustainable utilization of spent LIBs.
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The traditional hydrolysis-cooling-adsorption process for coke oven gas (COG) desulfurization urgently needs to be improved because of its complex nature and high energy consumption. One promising alternative for replacing the last two steps is selective catalytic oxidation. However, most catalysts used in selective catalytic oxidation require a high temperature to achieve effective desulfurization. Herein, a robust 30Fe-MCM41 catalyst is developed for direct desulfurization at medium temperatures after hydrolysis. This catalyst exhibits excellent stability for over 300 h and a high breakthrough sulfur capacity (2327.6 mgS gcat-1). Introducing Ag into the 30Fe-MCM41 (30Fe5Ag-MCM41) catalyst further enhances the H2S removal efficiency and sulfur selectivity at 120 °C. Its outstanding performance can be attributed to the synergistic effect of Fe-Ag clusters. During H2S selective oxidation, Fe serves as the active site for H2S adsorption and dissociation, while Ag functions as the catalyst promoter, increasing Fe dispersion, reducing the oxidation capacity of the catalyst, improving the desorption capacity of sulfur, and facilitating the reaction between active oxygen species and [HS]. This process provides a potential route for enhancing COG desulfurization.
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Coque , Sulfuro de Hidrógeno , Adsorción , Hidrógeno , Sulfuros , TemperaturaRESUMEN
BACKGROUND: Afidopyropen is a novel biorational insecticide for controlling piercing pests with great potential for application in tea gardens that can form the metabolite M440I007 when utilized for crops. However, because of a lack of analytical method for afidopyropen and M440I007 in tea, there is no means of monitoring the residues. Therefore, method development, validation and simultaneous determination of afidopyropen and M440I007 in fresh tea leaves, dried tea and tea infusion is of prime significance. RESULTS: A TPT cartridge-based method was developed for the solid phase extraction of afidopyropen and M440I007 from tea matrices. Extraction and clean-up conditions, including the composition, volume and temperature of elutions, were optimized to achieve the best results. Both targets were extracted using water and acetonitrile, with a water:acetonitrile (v/v) ratio of 4:10 for fresh leaves and 8:10 for dried tea, which were then cleaned and analyzed using ultraperformance liquid chromatography-tandem mass spectrometry. Both analytes demonstrated excellent linearity with a correlation coefficient above 0.998. The optimized analytical method offered limits of quantifications of 0.005, 0.005 and 0.002 mg kg-1 (converted to dried tea) in fresh tea shoots, dried tea and tea infusion for both targets, respectively. Average recoveries of afidopyropen and M440I007 ranged from 79.0% to 101.5%, with relative standard deviations ≤ 14.7%. CONCLUSION: The results showed that the method of determination for these insecticides in tea matrices was practical and efficient. © 2023 Society of Chemical Industry.
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Insecticidas , Espectrometría de Masas en Tándem , Espectrometría de Masas en Tándem/métodos , Té/química , Insecticidas/análisis , Cromatografía Líquida de Alta Presión/métodos , Extracción en Fase Sólida , Acetonitrilos/análisis , AguaRESUMEN
Plant byproducts and waste present enormous environmental challenges and an opportunity for valorization and industrial application. Due to consumer demands for natural compounds, the evident paucity of novel antimicrobial agents against foodborne pathogens, and the urgent need to improve the arsenal against infectious diseases and antimicrobial resistance (AMR), plant byproduct compounds have attracted significant research interest. Emerging research highlighted their promising antimicrobial activity, yet the inhibitory mechanisms remain largely unexplored. Therefore, this review summarizes the overall research on the antimicrobial activity and inhibitory mechanisms of plant byproduct compounds. A total of 315 natural antimicrobials from plant byproducts, totaling 1338 minimum inhibitory concentrations (MIC) (in µg/mL) against a broad spectrum of bacteria, were identified, and a particular emphasis was given to compounds with high or good antimicrobial activity (typically <100 µg/mL MIC). Moreover, the antimicrobial mechanisms, particularly against bacterial pathogens, were discussed in-depth, summarizing the latest research on using natural compounds to combat pathogenic microorganisms and AMR. Furthermore, safety concerns, relevant legislation, consumer perspective, and current gaps in the valorization of plant byproducts-derived compounds were comprehensively discussed. This comprehensive review covering up-to-date information on antimicrobial activity and mechanisms represents a powerful tool for screening and selecting the most promising plant byproduct compounds and sources for developing novel antimicrobial agents.
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Antiinfecciosos , Extractos Vegetales , Extractos Vegetales/farmacología , Antiinfecciosos/farmacología , Bacterias , Pruebas de Sensibilidad MicrobianaRESUMEN
Because of the high heterogeneity of breast cancer outcome, identification of novel prognostic biomarkers is critical to improve patient stratification and guide precise treatment. We examined the prognostic value of gamma-interferon-inducible lysosomal thiol reductase (GILT) expression in a training set of 416 breast cancer patients and a validation set of 210 patients, and performed functional studies to investigate the functions and underlying mechanisms of GILT on breast cancer prognosis. Our results indicated that high GILT expression in breast cancer cells was associated with improved disease-free survival (DFS; hazard ratio [HR] = 0.189, 95% confidence interval [CI]: 0.099-0.361) and breast cancer-specific survival (BCSS; HR = 0.187, 95% CI: 0.080-0.437) of breast cancer patients both in the training set and the external validation set (HR = 0.453, 95% CI: 0.235-0.873 for DFS, HR = 0.488, 95% CI: 0.245-0.970 for BCSS). In vitro and in vivo studies showed that GILT overexpression inhibited breast cancer cells proliferation, invasion, migration and tumor formation in nude mice and increased sensitivity of breast cancer cells to standard treatment. Proteomics analysis indicated that GILT inhibited reactive oxygen species (ROS) and autophagy activation in breast cancer cells, and GILT overexpression-mediated tumor growth was further enhanced in the presence of autophagy or ROS inhibitors. Our results demonstrate that GILT expression can be effectively used to predict the prognosis and guide treatment strategies of breast cancer patients.
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Neoplasias de la Mama/mortalidad , Oxidorreductasas actuantes sobre Donantes de Grupos Sulfuro/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Autofagia/fisiología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Femenino , Humanos , Persona de Mediana Edad , Oxidorreductasas actuantes sobre Donantes de Grupos Sulfuro/análisis , Pronóstico , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The proper disposals of spent lithium-ion batteries (LIBs) and volatile organic compounds (VOCs) both have a significant impact on the environment and human health. In this work, different morphologies of α-MnO2 catalysts are synthesized using a manganese-based compound as the precursor which is high-selectively recovered from spent lithium-ion ternary batteries. Different synthesis methods including the co-precipitation method, hydrothermal method, and impregnation method are used to prepare different morphologies of α-MnO2 catalysts and their catalytic activities of toluene oxidation are investigated. Experimental results show that MnO2-HM-140 with stacked nanorods synthesized using the hydrothermal method exhibits the best catalytic performance of toluene oxidation (T90 of 226 °C under the WHSV of 60,000 mL g-1·h-1), which could be attributed to its better redox ability at low temperature and much more abundant adsorbed oxygen species at low temperature. The adsorption abilities of toluene and the replenish rate of surface lattice oxygen can be enhanced due to the increase of oxygen vacancies on the surface of MnO2-HM-140. Furthermore, the results of in-situ DRIFTS and TD/GC-MS imply that benzoate species are the main intermediate groups and then the reaction pathway of toluene oxidation on the surface of MnO2-HM-140 is proposed.
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Compuestos de Manganeso , Compuestos Orgánicos Volátiles , Benzoatos , Humanos , Litio , Manganeso , Óxidos , Oxígeno , ToluenoRESUMEN
BACKGROUND: Despite novel advances in screening, targeting and immunotherapies, early diagnosis and satisfactory treatments against hepatocellular carcinoma (HCC) remain formidable challenges. Given the unique advantages, carbon quantum dots (CQDs) become a smart theranostic nanomaterial for cancer diagnosis and therapy. RESULTS: In this work, a type of bio-friendly CQDs, trichrome-tryptophan-sorbitol CQDs (TC-WS-CQDs), is synthesized from natural biocompatible tryptophan via the one-pot hydrothermal method. Compared with normal hepatocytes, a much stronger green fluorescence is detected in HCC cells, indicating the ability of TC-WS-CQDs to target HCC cells. Furthermore, green-emitting TC-WS-CQDs generate large amounts of reactive oxygen species (ROS), leading to autophagy of HCC cells. Additionally, the green-emitting TC-WS-CQDs perform significant tumor inhibition by inducing autophagy via p53-AMPK pathway in vitro and in vivo studies with almost no systemic toxicity. CONCLUSIONS: The results may highlight a promising anticancer nanotheranostic strategy with integration of diagnosis, targeting, and therapy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Puntos Cuánticos , Carbono/farmacología , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Medicina de Precisión , Sorbitol , TriptófanoRESUMEN
Nonconventional luminescence polymers without any aromatic structures have attracted great interest from researchers due to their special structure and excellent biocompatibility. However, these materials mostly emit in the blue or green region, in which preparation of materials with long-wavelength (especially near-infrared) emission is still a great challenge. In this work, it is found that 2-(dimethyl amino) ethyl methacrylate (DMA) and itaconic anhydride (ITA) undergo a ring-opening reaction at room temperature, and subsequently generate zwitterionic compound (IDMA). Based on the clustering-triggered emission (CTE) mechanism, ionic bond can effectively promote the isolated electron-rich chromophores to form new emissive clusters with extended electron delocalization. Herein, two oligomers (P1 and P2) with different fluorescence emissions by controlling the concentration of zwitterionic monomers before polymerization are synthesized. It is worth noting that the maximum emission wavelength of P2 at high concentration is up to 712 nm, which is very rare in previous reports. In addition, the resulting oligomer (P2) shows typical aggregation-enhanced emission (AEE), excitation-dependent fluorescence, temperature-sensitive emission, and solvatochromism. The cytotoxicity assay demonstrates that P2 was low toxic to Huh7 and LM3 cells, and suitable for cell imaging. This research provides the possibility for rational molecular design and the feasibility of luminescence regulation.
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Luminiscencia , Polímeros , Fluorescencia , Polimerizacion , TemperaturaRESUMEN
Due to the sustainable use of wastes, cathode materials of spent lithium-ion batteries are recovered and used as transition metal precursors to prepare metal oxides catalysts for the oxidation of VOCs. In this work, a series of manganese-based and cobalt-based metal oxides are synthesized via different preparation methods. Catalytic activities of the catalysts prepared are investigated through complete oxidation of oxygenated VOCs and the physicochemical properties of optimum samples are characterized. Evaluation results indicate that MnOx (SY) (HT) sample prepared via hydrothermal method and CoOx (GS) (CP) synthesized via co-precipitation method had better performance, because they have higher specific surface area, higher concentration of active oxygen species and high-valence metal ion, as well as better low-temperature reducibility compared to the other multi-metal oxides used in the study. In addition, TD/GC-MS results imply that further oxidation of by-products requires high reaction temperature during VOCs oxidation.
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Suministros de Energía Eléctrica , Litio , Electrodos , Metales , Óxidos , ReciclajeRESUMEN
Drug resistance of tumor cells is always a headache problem in clinical treatment. In order to combat chemotherapy-resistance in cervical cancer and improve treatment effect, we design a CRISPR/Cas9 nanoeditor to knock out two key oncogenes E6 and E7 that lead to drug tolerance. Meanwhile, the deletion of these two oncogenes can effectively reactivate p53 and pRB signaling pathways that inhibit the growth of tumor cells. Our results demonstrated the nanoeditor could simultaneously delete two oncogenes, and the size of DNA fragments knocked out reaches an unprecedented 563 bp. After the preparation of cationic liposomes combined with chemotherapy drug docetaxel (DOC), this nanosystem can significantly inhibit the drug tolerance of cancer cells and improve the therapeutic effect of cervical cancer. Therefore, this study provides a promising strategy for the treatment of cervical cancer by combining chemotherapy and double-target gene therapy. This strategy can also be applied in other disease models to customize personalized anti-tumor strategies by simply changing chemotherapy drugs and targeted genes.
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Sistemas CRISPR-Cas , Resistencia a Antineoplásicos , Técnicas de Inactivación de Genes , Oncogenes/genética , Neoplasias del Cuello Uterino/terapia , Animales , Apoptosis/efectos de los fármacos , Modelos Animales de Enfermedad , Femenino , Marcación de Gen , Terapia Genética , Células HeLa , Humanos , Ratones , Ratones Desnudos , Nanomedicina , Nanopartículas , Neoplasias del Cuello Uterino/genéticaRESUMEN
The COVID-19 pandemic caused by SARS-CoV-2 seriously threatens global public health. It has previously been confirmed that SARS-CoV-2 is mainly transmitted between people through "respiratory droplets". Therefore, the respiratory tract mucosa is the first barrier to prevent virus invasion. It is very important to stimulate mucosal immunity to protect the body from respiratory virus infection. Inspired by this, we designed a bionic-virus nanovaccine, which can induce mucosal immunity by nasal delivery to prevent virus infection from respiratory tract. The nanovaccine that mimic virosome is composed of poly(I:C) mimicking viral genetic material as immune adjuvant, biomimetic pulmonary surfactant (bio-PS) liposomes as capsid structure of virus and the receptor binding domains (RBDs) of SARS-CoV-2 as "spike" to completely simulate the structure of the coronavirus. The nanovaccine can be administered by inhaling to imitate the process of SARS-CoV-2 infection through the respiratory tract. Our results demonstrated that the inhalable nanovaccine with bionic virus-like structure has a stronger mucosal protective effect than routine muscle and subcutaneous inoculation. In particular, high titer of secretory immunoglobulin A (sIgA) was detected in respiratory secretions, which effectively neutralize the virus and prevent it from entering the body through the respiratory tract. Through imitating the structure and route of infection, this inhalable nanovaccine strategy might inspire a new approach to the precaution of respiratory viruses.
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BACKGROUND: Pymetrozine is a widely used pesticide. It is challenging to analyze and difficult to manage due to the large gap in its global maximum residue limits (MRLs) in tea. The development of a high-efficiency detection method for the evaluation of the transfer of residual pymetrozine from tea plantations to tea cups is therefore of prime significance. RESULTS: An analytical method for the determination of pymetrozine residues in tea was established based on Cleanert PCX solid-phase extraction. The average recoveries were 72.2-93.7%, with relative standard deviations (RSDs) of less than 12%. The limits of quantification (LOQs) were 0.005 mg·kg-1 in fresh tea leaves and dry tea, and 0.00025 mg·L-1 in tea brew. Pymetrozine degraded rapidly in tea plants with a half-life (t1/2 ) of 1.9 days in open tea plantations, and decreased by 9.4-23.7% in the green tea-processing procedure, which was concentration dependent. The residual pymetrozine levels in green tea collected at 6 and 21 days were below the MRLs in China and EU at a dosage of 30 g a.i. ha-1 , respectively. The leaching rates of pymetrozine from dry tea to tea brew were 58.7-96.3%. Hazard quotient (HQ) values of pymetrozine were significantly <100% when tea shoots were plucked in 6 days, which indicated a negligible risk to humans. CONCLUSION: This work allows the determination of residual pymetrozine in tea and illustrates a low intake risk with the use of pymetrozine in tea plantations. It could serve as reference for further regulation consideration for maximum residue limits (MRLs). © 2020 Society of Chemical Industry.
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Camellia sinensis/química , Contaminación de Alimentos/análisis , Residuos de Plaguicidas/análisis , Té/química , Triazinas/análisis , ChinaRESUMEN
Microbial growth and fluctuations in environmental conditions have been shown to cause microbial contamination and deterioration of food. Thus, it is paramount to develop reliable strategies to effectively prevent the sale and consumption of contaminated or spoiled food. Responsive packaging systems are designed to react to specific stimuli in the food or environment, such as microorganisms or temperature, then implement an informational or corrective response. Informative responsive packaging is aimed at continuously monitoring the changes in food or environmental conditions and conveys this information to the users in real time. Meanwhile, packaging systems with the capacity to control contamination or deterioration are also of great interest. Encouragingly, corrective responsive packaging attempting to mitigate the adverse effects of condition fluctuations on food has been investigated. This packaging exerts its effects through the triggered release of active agents by environmental stimuli. In this review, informative and corrective responsive packaging is conceptualized clearly and concisely. The mechanism and characteristics of each type of packaging are discussed in depth. This review also summarized the latest research progress of responsive packaging and objectively appraised their advantages. Evidently, the mechanism through which packaging systems respond to microbial contamination and associated environmental factors was also highlighted. Moreover, risk concerns, related legislation, and consumer perspective in the application of responsive packaging are discussed as well. Broadly, this comprehensive review covering the latest information on responsive packaging aims to provide a timely reference for scientific research and offer guidance for presenting their applications in food industry.
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Embalaje de Alimentos , Conservación de Alimentos , Granjas , Contaminación de Alimentos/prevención & control , Calidad de los AlimentosRESUMEN
In designing organic semiconductors for organic devices, halogenation is a very popular strategy for tuning the electronic properties and packing arrangement in the solid state. Herein, we report the synthesis and characterization of halogenated dibenzo[a,j]perylene (DBP) with triethylsilyl (TES)-ethynyl substituents at the 8- and 16-positions (TES-DBP). The resulting compounds are characterized by optical, electrochemical, crystallographic, and computational studies to clarify the effect of halogenation on the optoelectronic properties and charge-carrier transport. It is found that the halogen atoms, the degree of halogenation, and their positional locations can alter the electronic properties and crystal packing of the compounds. In contrast to fluorinated TES-DBP, the chlorinated counterpart has red-shifted maximum absorption and lower electron affinity owing to the electron delocalization between DBP core and the unoccupied 3d orbitals of Cl atom. Organic field-effect transistor measurements demonstrate that TES-2ClDBP shows a hole mobility of 0.25 cm2 V-1 s-1, which is higher than TES-2FDBP and TES-DBP. On the other hand, TES-4ClDBP exhibits ambipolar transport characteristics with electron and hole mobilities up to 0.02 and 0.07 cm2 V-1 s-1, respectively.
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This study evaluated the inactivation effect of ultrasonic treatment combined with acidic electrolyzed water (AEW) on Bacillus cereus spores. AEW treatment reduced the spores by 1.05-1.37 log CFU/mL while the sporicidal effect of ultrasound was minor. More strikingly, simultaneous ultrasonic and AEW treatments for 30 min led to 2.29 log CFU/mL reduction and thus, considered a synergistic effect. Flow cytometry combined with SYTO/PI staining analysis revealed that ultrasound hydrolyzed the cortex while the AEW partially damaged the integrity of the inner membrane. Scanning and transmission electron microscopies were used to characterize the ultrastructural changes. The detachment of the exosporium induced by ultrasound was the most apparent difference compared with the control group, and the electron density of spores appeared to be heterogeneous after treatment with AEW. These results indicated that combining ultrasound with AEW is a promising decontamination technology with potential uses in the food industry and environmental remediation.
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Ácidos/farmacología , Antibacterianos/farmacología , Bacillus cereus/efectos de los fármacos , Viabilidad Microbiana/efectos de los fármacos , Esporas Bacterianas/efectos de los fármacos , Ondas Ultrasónicas , Agua/química , Desinfectantes/farmacología , Electrólisis , Industria de Alimentos/métodos , Concentración de Iones de Hidrógeno , Agua/farmacologíaRESUMEN
The research of robotic autonomous radioactivity detection or radioactive source search plays an important role in the monitoring and disposal of nuclear safety and biological safety. In this paper, a method for autonomously searching for radioactive sources through mobile robots was proposed. In the method, by using a partially observable Markov decision process (POMDP), the search of autonomous unknown radioactive sources was realized according to a series of radiation information measured by mobile robot. First, the factors affecting the accuracy of radiation measurement during the robot's movement were analyzed. Based on these factors, the behavior set of POMDP was designed. Secondly, the parameters of the radioactive source were estimated in the Bayesian framework. In addition, through the reward strategy, autonomous navigation of the robot to the position of the radiation source was achieved. The search algorithm was simulated and tested, and the TurtleBot robot platform was used to conduct a real search experiment on the radio source Cs-137 with an activity of 37 MBq indoors. The experimental results showed the effectiveness of the method. Additionally, from the experiments, it could been seen that the robot was affected by the linear velocity, angular velocity, positioning accuracy and the number of measurements in the process of autonomous search for the radioactive source. The proposed mobile robot autonomous search method can be applied to the search for lost radioactive sources, as well as for the leakage of substances (nuclear or chemical) in nuclear power plants and chemical plants.
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BACKGROUND: The functional properties of whey protein isolate (WPI) are sensitive to pH, ionic strength, and temperature. This prevents its application in various food systems and processing technologies. The conjugation of proteins with polysaccharides via the Maillard reaction is an efficient method to improve the functionality of proteins. The purpose of this work was to conjugate gum acacia (GA) with WPI via the dry-heating Maillard reaction and to investigate the effect of reaction time on the physicochemical and functional properties of WPI-GA conjugates. RESULTS: Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and high-performance size exclusion chromatography confirmed the formation of higher molecular weight conjugates. The degrees of glycation for WPI-GA conjugates incubated for 1, 3, 5, and 7 days were 28.14%, 44.98%, 49.50%, and 51.20%, respectively. The glycation reaction reduced the surface hydrophobicity and fluorescence intensity of WPI significantly (P < 0.05). Functional properties of the conjugates, such as solubility, stability against heat-induced insolubility, and emulsion properties were all superior to the control WPI. However, a reaction time longer than a day resulted in a high degree of browning and decreased the functionality of the conjugate significantly (P < 0.05). CONCLUSION: The results indicated that conjugation of WPI with GA can be a promising way to enhance its functional properties. However, the reaction time suitable for producing conjugates with superior functional properties was not necessarily the highest glycation degree that could be reached. © 2019 Society of Chemical Industry.
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Goma Arábiga/química , Proteína de Suero de Leche/química , Cromatografía en Gel , Color , Electroforesis en Gel de Poliacrilamida , Emulsiones/química , Glicosilación , Interacciones Hidrofóbicas e Hidrofílicas , Reacción de Maillard , Peso Molecular , Concentración Osmolar , SolubilidadRESUMEN
Antibodies targeting PD-1 have been demonstrated durable anti-cancer activity in certain cancer types. However, the anti-PD-1 antibodies are less or not efficacious in many situations, which might be attributed to co-expression of multiple inhibitory receptors or presence of immunosuppressive cells in the tumor microenvironment. Most of the anti-PD-1 antibodies used in clinical studies are of IgG4 isotype with the S228P mutation (IgG4S228P). The functional impact by the interaction of anti-PD-1 IgG4S228P antibody with Fc gamma receptors (FcγRs) is poorly understood. To assess the effects, we generated a pair of anti-PD-1 antibodies: BGB-A317/IgG4S228P and BGB-A317/IgG4-variant (abbreviated as BGB-A317), with the same variable regions but two different IgG4 Fc-hinge sequences. There was no significant difference between these two antibodies in binding to PD-1. However, BGB-A317/IgG4S228P binds to human FcγRI with high affinity and mediates crosslinking between PD-1 and FcγRI. In contrast, BGB-A317 does neither. Further cell-based assays showed that such crosslinking could reverse the function of an anti-PD-1 antibody from blocking to activating. More importantly, the crosslinking induces FcγRI+ macrophages to phagocytose PD-1+ T cells. In a mouse model transplanted with allogeneic human cancer cells and PBMCs, BGB-A317 showed significant tumor growth inhibition, whereas BGB-A317/IgG4S228P had no such inhibition. Immunohistochemistry study revealed an inverse correlation between FcγRI+ murine macrophage infiltration and the density of CD8+PD-1+ human T cells within tumors in the BGB-A317/IgG4S228P-treated group. These evidences suggested that FcγRI+ binding and crosslinking had negative impact on the anti-PD-1 antibody-mediated anti-cancer activity.
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Anticuerpos Monoclonales/farmacología , Carcinoma de Células Escamosas/inmunología , Inmunoglobulina G/inmunología , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptores de IgG/metabolismo , Neoplasias Cutáneas/inmunología , Animales , Apoptosis , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/metabolismo , Proliferación Celular , Humanos , Inmunoglobulina G/efectos de los fármacos , Inmunoglobulina G/metabolismo , Activación de Linfocitos , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones , Ratones Endogámicos NOD , Ratones SCID , Receptor de Muerte Celular Programada 1/inmunología , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/metabolismo , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Linfocitos T/metabolismo , Células Tumorales Cultivadas , Microambiente Tumoral , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
INTRODUCTION: Although obesity has been reported worldwide as a risk factor for breast cancer, there are still some inconsistencies regarding the association between obesity and breast cancer. Body mass index (BMI) is used most to assess the extent of obesity; however, the association of other body size characteristics, such as waist and hip circumference, with susceptibility to breast cancer in Chinese Han women needs to be better assessed. PATIENTS AND METHODS: Female Chinese Han patients (N = 2,800) were recruited from 21 hospitals in northern and eastern China from April 2012 to April 2013 for a case-control study. The significant differences of factors related to body size between the breast-cancer case and control groups were determined by Student's t test and chi-square tests. RESULTS: Premenopausal women with breast cancer had higher BMI and larger waist and hip circumferences (p = 2 × 10-4, <1 × 10-6, and 2 × 10-5, respectively). However, these body-size factors were not associated with postmenopausal breast cancer (p = .45, 0.32, and 0.12, respectively). BMI between 28 and 30 kg/m2 or greater than 32 kg/m2 was related to breast cancer incidence in the overall study population and in premenopausal women but not in the postmenopausal group. CONCLUSION: Obesity is significantly associated with breast cancer in Chinese Han premenopausal women but not in postmenopausal women. Thus, it is important to realize that weight control, as well as avoiding abdominal obesity, should be considered as one of the most effective methods of reducing breast cancer risk. IMPLICATIONS FOR PRACTICE: To better understand the characteristics and risk factors for breast cancer in Han women in northern and eastern China, a case-control study of 2,800 Chinese Han women was conducted. Obesity was significantly associated with breast cancer in Chinese Han premenopausal women but not in postmenopausal women. Consequently, controlling body weight and avoiding abdominal obesity should be considered as one of the most effective methods of reducing breast cancer susceptibility. However, the diversity between this study's finding among Chinese Han women and other data previously reported among European and American populations still needs further investigation.