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The significant health risks of nanoplastics (NPs) and cadmium (Cd) are currently attracting a great deal of attention and research. At present, the effects and mechanisms of NPs and Cd on human serum albumin (HSA), a key functional protein in the organism on transportation, remain unknown. Here, the differences in the effects and mechanisms of action of Cd alone and composite systems (NPsCd) were explored by enzyme activity assay, multi-spectroscopy analysis and molecular docking. The results showed that HSA activity was inhibited and decreased to 80â¯% and 69.55â¯% (Cdâ¯=â¯30â¯mg/L) by Cd alone and NPs-Cd exposure, respectively. Exposure to Cd induced backbone disruption and protein defolding of HSA, and secondary structure disruption was manifested by the reduction of α-helix. Cd exposure also induces fluorescence sensitization of HSA. Notably, the addition of NPs further exacerbated the effects associated with Cd exposure, which was consistent with the changes in HSA activity. Thus, the above conformational changes may be responsible for inducing the loss of enzyme activity. Moreover, it was determined by RLS spectroscopy that NPs-Cd bound to HSA in the form of protein crowns. Molecular docking has further shown that Cd binds to the surface of Sudlow site II of HSA, suggesting that Cd impairs the function of HSA by affecting the protein structure. More importantly, the addition of NPs further exacerbated the disruption of the protein structure by the adherent binding of HSA on the surface of the plastic particles, which induced a greater change in the enzyme activity. This study provides useful perspectives for investigating the impact of composite pollution on HSA of human functional proteins.
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Zearalenone contaminates food and poses a threat to human health. It is vital to develop cost-effective and environmentally-friendly adsorbents for its removal. By screening Sporobolomyces pararoseus (SZ4) and modified yam starch (adsorption capacity (qe) of 1.33 and 0.94 mg/g, respectively), this study prepared a novel composite aerogel adsorbent (P-YSA@SZ410). The compressive strength of P-YSA@SZ410 was 1.35-fold higher than unloaded yeast. It contained several functional groups and three-dimensional interconnected channels, achieving a 0° contact angle within 0.18 s, thereby demonstrating excellent water-absorbent properties. With a qe of 2.96 mg/g at 308 K, the adsorption process of P-YSA@SZ410 was spontaneous, endothermic, and matched pseudo-second-order and Langmuir models. The composite adsorbed zearalenone via electrostatic attraction and hydrogen bonding, maintaining a qe of 2.24 mg/g after five cycles. P-YSA@SZ410 was found to remove zearalenone effectively under various conditions and could be applied to corn silk tea, indicating its great potential as an adsorbent material.
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HFC-125 and HFC-32 are fluorinated greenhouse gases of great concern due to their high GWPs and increasing background atmospheric concentrations. Long-term atmospheric observations of HFC-125 and HFC-32 were carried out in four representative cities of China (Beijing, Guangzhou, Hangzhou, and Lanzhou) from January 2012 to October 2019. Overall, the annual mean atmospheric concentrations of HFC-125 and HFC-32 both showed increasing trends, with average rates of 4.8â¯pptâ¯yr-1 and 7.9â¯pptâ¯yr-1. The average concentrations of HFC-125 and HFC-32 in urban areas were significantly higher than those in suburban areas. Significant differences in atmospheric concentrations of the two HFCs were observed among the four cities. HFC-125 and HFC-32 emissions were estimated accordingly, averaging 6.2 Gg yr-1 (23.6 Mt. CO2-eq) and 5.7 Gg yr-1 (4.3 Mt. CO2-eq) during 2012 and 2019 and growing at rates of 0.8 Gg yr-1 (3.1 Mt. CO2-eq) and 0.8 Gg yr-1 (0.6 Mt. CO2-eq), respectively, with an increasing contribution to global radiative forcing. The bottom-up inventories of HFC-125 and HFC-32 in the four cities increased annually from 2012 to 2019, with the highest emissions in Beijing, while the top-down emissions fluctuated during the research period. SYNOPSIS: The atmospheric concentrations of HFC-125 and HFC-32 were measured from 2012 to 2019 in four representative cities of China. Both HFC emissions at national and city levels were estimated using observation-based and inventory methods.
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The twisted bilayer system provides an excellent platform for the study of flatbands. In this work, we propose a bilayer hexagonal boron nitride (h-BN)-like surface plasmon crystal at a large twist angle of 38.213° due to the interlayer strong coupling, in which the adjacent pillars are in different radii. We numerically and theoretically calculate the band structure while tuning the pillar radius ratio (PRR) and the interlayer separation distance. As a result, both increasing the PRR and decreasing the separation distance contribute to the transition from weak coupling to strong coupling, leading to the flatbands with slow velocity and large density of state. Consequently, the in-layer geometry as well as the separation distance offers the degree of freedom to achieve flatbands in the bilayer surface plasmon crystal. Our work provides a fundamental understanding of the band structure of the twisted bilayer photonic system, which enriches the methods to obtain flatbands at a large twist angle.
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Salmonella in raw cocoa beans (nâ¯=â¯870) from main sourcing areas over nine months was analyzed. It was detected in 71 (ca. 8.2%) samples, with a contamination level of 0.3-46 MPN/g except for one sample (4.1â¯×â¯104 CFU/g). Using prevalence and concentration data as input, the impact of thermal treatment in cocoa processing on the risk estimate of acquiring salmonellosis by a random Belgian chocolate consumer was calculated by a quantitative microbiological risk assessment (QMRA) approach. A modular process risk model from raw cocoa beans to cocoa liquor up to a hypothetical final product (70-90% dark chocolate tablet) was set up to understand changes in Salmonella concentrations following the production process. Different thermal treatments during bean or nib steam, nib roasting, or liquor sterilization (achieving a 0-6 log reduction of Salmonella) were simulated. Based on the generic FAO/WHO Salmonella dose-response model and the chocolate consumption data in Belgium, salmonellosis risk per serving and cases per year at population level were estimated. When a 5 log reduction of Salmonella was achieved, the estimated mean risk per serving was 3.35â¯×â¯10-8 (95% CI: 3.27â¯×â¯10-10-1.59â¯×â¯10-7), and estimated salmonellosis cases per year (11.7 million population) was 88 (95% CI: <1-418). The estimated mean risk per serving was 3.35â¯×â¯10-9 (95% CI: 3.27â¯×â¯10-11-1.59â¯×â¯10-8), and the estimated salmonellosis cases per year was 9 (95% CI: <1-42), for a 6 log reduction. The current QMRA model solely considered Salmonella reduction in a single-step thermal treatment in the cocoa process. Inactivation obtained during other process steps (e.g. grinding) might occur but was not considered. As the purpose was to use QMRA as a tool to evaluate the log reduction in the cocoa processing, no postcontamination from the processing environment and ingredients was included. A minimum of 5 log reduction of Salmonella in the single-step thermal treatment of cocoa process was considered to be adequate.
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Injectable, self-crosslinking collagen-based hydrogels are beneficial for chondrocytes to secrete matrix, positioning them as promising candidates for cartilage tissue engineering. However, previous studies lacked insight into the ability of cell-free collagen-based hydrogels to regenerate hyaline cartilage defect. Therefore, this study aimed to evaluate the potential of collagen-based hydrogels (Col and ColHA) to induce chondrogenic differentiation of stem cells and in situ hyaline cartilage regeneration. Both Col and ColHA hydrogels self-crosslinked in situ and exhibited similar physical properties. In vitro experiments showed they supported the survival, adhesion, spreading, and proliferation of bone marrow stem cells (BMSCs). Moreover, both hydrogels induced ectopic differentiation of BMSCs into chondrocytes when implanted subcutaneously into the back of nude mice. ColHA hydrogel notably enhanced type II collagen secretion. The results of repairing cartilage defects in situ revealed both hydrogels facilitated hyaline cartilage regeneration and maintained cartilage phenotype without exogenous BMSCs. Hydrogels encapsulating BMSCs expedited cartilage repair, and ColHA/BMSC constructs showed better mechanical properties, suggesting their potential for cartilage repair applications. This study implies that collagen-based hydrogels are good candidates for hyaline cartilage regeneration.
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The perfluorocarbons tetrafluoromethane (CF4, PFC-14) and hexafluoroethane (C2F6, PFC-116) are potent greenhouse gases with near-permanent atmospheric lifetimes relative to human timescales and global warming potentials thousands of times that of CO2. Using long-term atmospheric observations from a Chinese network and an inverse modeling approach (top-down method), we determined that CF4 emissions in China increased from 4.7 (4.2-5.0, 68% uncertainty interval) Gg y-1 in 2012 to 8.3 (7.7-8.9) Gg y-1 in 2021, and C2F6 emissions in China increased from 0.74 (0.66-0.80) Gg y-1 in 2011 to 1.32 (1.24-1.40) Gg y-1 in 2021, both increasing by approximately 78%. Combined emissions of CF4 and C2F6 in China reached 78 Mt CO2-eq in 2021. The absolute increase in emissions of each substance in China between 2011-2012 and 2017-2020 was similar to (for CF4), or greater than (for C2F6), the respective absolute increase in global emissions over the same period. Substantial CF4 and C2F6 emissions were identified in the less-populated western regions of China, probably due to emissions from the expanding aluminum industry in these resource-intensive regions. It is likely that the aluminum industry dominates CF4 emissions in China, while the aluminum and semiconductor industries both contribute to C2F6 emissions. Based on atmospheric observations, this study validates the emission magnitudes reported in national bottom-up inventories and provides insights into detailed spatial distributions and emission sources beyond what is reported in national bottom-up inventories.
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Type I collagen (Col I) and hyaluronic acid (HA), derived from the extracellular matrix (ECM), have found widespread application in cartilage tissue engineering. Nevertheless, the potential of cell-free collagen-based scaffolds to induce in situ hyaline cartilage regeneration and the related mechanisms remain undisclosed. Here, we chose Col I and HA to construct Col I hydrogel and Col I-HA composite hydrogel with similar mechanical properties, denoted as Col and ColHA, respectively. Their potential to induce cartilage regeneration was investigated. The results revealed that collagen-based hydrogels could regenerate hyaline cartilage without any additional cells or growth factors. Notably, ColHA hydrogel stood out in this regard. It elicited a moderate activation, recruitment, and reprogramming of macrophages, thus efficiently mitigating local inflammation. Additionally, ColHA hydrogel enhanced stem cell recruitment, facilitated their chondrogenic differentiation, and inhibited chondrocyte fibrosis, hypertrophy, and catabolism, thereby preserving cartilage homeostasis. This study augments our comprehension of cartilage tissue induction theory by enriching immune-related mechanisms, offering innovative prospects for the design of cartilage defect repair scaffolds. STATEMENT OF SIGNIFICANCE: The limited self-regeneration ability and post-injury inflammation pose significant challenges to articular cartilage repair. Type I collagen (Col I) and hyaluronic acid (HA) are extensively used in cartilage tissue engineering. However, their specific roles in cartilage regeneration remain poorly understood. This study aimed to elucidate the functions of Col I and Col I-HA composite hydrogels (ColHA) in orchestrating inflammatory responses and promoting cartilage regeneration. ColHA effectively activated and recruited macrophages, reprogramming them from an M1 to an M2 phenotype, thus alleviating local inflammation. Additionally, ColHA facilitated stem cell homing, induced chondrogenesis, and concurrently inhibited fibrosis, hypertrophy, and catabolism, collectively contributing to the maintenance of cartilage homeostasis. These findings underscore the clinical potential of ColHA for repairing cartilage defects.
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Global atmospheric emissions of perfluorocyclobutane (c-C4F8, PFC-318), a potent greenhouse gas, have increased rapidly in recent years. Combining atmospheric observations made at nine Chinese sites with a Lagrangian dispersion model-based Bayesian inversion technique, we show that PFC-318 emissions in China grew by approximately 70% from 2011 to 2020, rising from 0.65 (0.54-0.72) Gg year-1 in 2011 to 1.12 (1.05-1.19) Gg year-1 in 2020. The PFC-318 emission increase from China played a substantial role in the overall increase in global emissions during the study period, contributing 58% to the global total emission increase. This growth predominantly originated in eastern China. The regions with high emissions of PFC-318 in China overlap with areas densely populated with polytetrafluoroethylene (PTFE) factories, implying that fluoropolymer factories are important sources of PFC-318 emissions in China. Our investigation reveals an emission factor of approximately 3.02 g of byproduct PFC-318 emissions per kg of hydrochlorofluorocarbon-22 (HCFC-22) feedstock use in the production of tetrafluoroethylene (TFE) (for PTFE production) and hexafluoropropylene (HFP) if we assume all HCFC-22 produced for feedstock uses in China are pyrolyzed to produce PTFE and HFP. Further facility-level sampling and analysis are needed for a more precise evaluation of emissions from these factories.
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Contaminantes Atmosféricos , Atmósfera , China , Contaminantes Atmosféricos/análisis , Atmósfera/química , Monitoreo del Ambiente , Fluorocarburos/análisis , Teorema de Bayes , Politetrafluoroetileno , CiclobutanosRESUMEN
Chromium (Cr) poses a high ecological risk, however the toxic mechanisms of Cr in different valence states to soil organisms at cellular and molecular levels are not exactly. In this study, the Eisenia fetida coelomocytes and Cu/Zn-superoxide dismutase (Cu/Zn-SOD) were chosen as the target subjects to investigate the effects and mechanisms of cellular toxicity induced by Cr(VI) and Cr(III). Results indicated that Cr(VI) and Cr(III) significantly reduced the coelomocytes viability. The level of reactive oxygen species (ROS) was markedly increased after Cr(VI) exposure, which finally reduced antioxidant defense abilities, and induced lipid peroxidation and cellular membrane damage in earthworm coelomocytes. However, Cr(III) induced lower levels of oxidative stress and cellular damage with respect to Cr(VI). From a molecular perspective, the binding of both Cr(VI) and Cr(III) with Cu/Zn-SOD resulted in protein backbone loosening and reduced ß-Sheet content. The Cu/Zn-SOD showed fluorescence enhancement with Cr(III), whereas Cr(VI) had no obvious effect. The activity of Cu/Zn-SOD continued to decrease with the exposure of Cr. Molecular docking indicated that Cr(III) interacted more readily with the active center of Cu/Zn-SOD. Our results illustrate that oxidative stress induced by Cr(VI) and Cr(III) plays an important role in the cytotoxic differences of Eisenia fetida coelomocytes and the binding of Cr with Cu/Zn-SOD can also affect the normal structures and functions of antioxidant defense-associated protein.
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Cromo , Oligoquetos , Estrés Oxidativo , Contaminantes del Suelo , Oligoquetos/fisiología , Oligoquetos/efectos de los fármacos , Animales , Cromo/toxicidad , Contaminantes del Suelo/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo , Simulación del Acoplamiento Molecular , Peroxidación de Lípido/efectos de los fármacosRESUMEN
Bacillus thuringiensis-based commercial products as a biopesticide have been used for more than 60 years in agriculture. However, as one of the species in B. cereus group, B. thuringiensis has been considered as an emerging hazard with the potential to cause food toxico-infections. The present study aimed to evaluate the biofilm-forming ability of B. thuringiensis biopesticide strains and their attachment on spinach, compared to foodborne B. cereus strains. Biofilm formations of tested strains were found to be strain-specific and affected by the nutrient conditions more than the incubation time. Nutrient starvation conditions generally reduced the biofilm formation of tested B. thuringiensis and B. cereus strains, particularly B. thuringiensis ABTS-1857 strain was found as the nonbiofilm former in starvation conditions. It is worth mentioning that B. thuringiensis SA-11 strain showed stronger biofilm-forming ability with more air-liquid interface biofilm than the other two B. thuringiensis biopesticide strains, but no such higher attachment of B. thuringiensis SA-11 to spinach was observed. These results indicate that B. thuringiensis SA-11 strain can enter the food processing lines by the attachment on spinach leaves, and it has the potential to form biofilms throughout the processing lines or the production environment when sufficient nutrients are available. However, more biofilm tests of B. thuringiensis biopesticide strains in the vegetable production chain should be performed. The dry formulation of commercial B. thuringiensis biopesticides enhanced their adhesion on spinach leaves, whereas the strength of adhesion was not improved by the formulation. In addition, 1-2 log reductions of spores after the intensive washing of spinach leaves in the lab were detected. However, the log reduction due to the actual washing done by the food processing companies in large-volume washing baths or by consumers at home would be limited and less than this lab simulation.
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Bacillus thuringiensis , Adhesión Bacteriana , Biopelículas , Spinacia oleracea , Bacillus thuringiensis/clasificación , Bacillus thuringiensis/fisiología , Bacillus cereus/fisiología , Agentes de Control Biológico , Spinacia oleracea/microbiología , Poliestirenos , Esporas Bacterianas/crecimiento & desarrollo , Esporas Bacterianas/fisiología , Especificidad de la EspecieRESUMEN
With increasing concerns about N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and 6PPD-quinone (6PPD-Q), relevant environmental investigations and toxicological research have sprung up in recent years. However, limited information could be found for human body burden assessment. This work collected and analyzed 200 samples consisting of paired urine and plasma samples from participants (50 male and 50 female) in Tianjin, China. Low detection frequencies (DF, <15 %) were found except for urinary 6PPD-Q (86 %), which suggested the poor residue tendency of 6PPD and 6PPD-Q in blood. The low DFs also lead to no substantial association between two chemicals. Data analysis based on urinary 6PPD-Q showed a significant difference between males and females (p < 0.05). No significant correlation was found for other demographic factors (Body Mass Index (BMI), age, drinking, and smoking). The mean values of daily excretion (ng/kg bw/day) calculated using urinary 6PPD-Q for females and males were 7.381 ng/kg bw/day (female) and 3.360 ng/kg bw/day (male), and apparently female suffered higher daily exposure. Further analysis with daily excretion and ALT (alanine aminotransferase)/TSH (thyroid stimulating hormone)/ blood cell analysis indicators found a potential correlation with 6PPD-Q daily excretion and liver/immune functions. Considering this preliminary assessment, systematic research targeting the potential organs at relevant concentrations is required.
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Fenilendiaminas , Humanos , Masculino , Femenino , China , Adulto , Persona de Mediana Edad , Adulto Joven , Contaminantes Ambientales/orina , Contaminantes Ambientales/sangre , QuinonasRESUMEN
The difference in the transport behaviors of nanoplastics consistently assistant with their toxicities to benthic and other aquatic organisms is still unclear between freshwater and marine sediments. Here, the mobilities of polystyrene nanoplastics (PSNPs) and key environmental factors including salinity and humic acid (HA) were systematically studied. In the sand column experiments, both tested PSNPs in the freshwater system (100 nm NPs (100NPs): 90.15 %; 500 nm NPs (500NPs): 54.22 %) presented much higher penetration ratio than in the marine system (100NPs: 8.09 %; 500NPs: 19.04 %). The addition of marine sediment with a smaller median grain diameter caused a much more apparent decline in NPs mobility (100NPs: from 8.09 % to 1.85 %; 500NPs: from 19.04 % to 3.51 %) than that containing freshwater sediment (100NPs: from 90.15 % to 83.56 %; 500NPs: from 54.22 % to 41.63 %). Interestingly, adding HA obviously led to decreased and slightly increased mobilities for NPs in freshwater systems, but dramatically improved performance for NPs in marine systems. Electrostatic and steric repulsions, corresponding to alteration of zeta potential and hydrodynamic diameter of NPs and sands, as well as minerals owing to adsorption of dissolved organic matter (DOM) and aggregations from varied salinity, are responsible for the mobility difference.
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Nanoplastics (NPs) are easily ingested by organisms and their major accumulation organ was determined to be liver. To date, the size-dependent cytotoxicity of NPs on mammalian hepatocytes remains unclear. This study utilized mouse primary hepatocytes and catalase (CAT) as specific receptors to investigate the toxicity of NPs from cells to molecules, focusing on size-dependent effects. Results showed that the larger the particle size of NP at low doses (≤50 mg/L), the most pronounced inhibitory effect on hepatocyte viability. 20 nm NPs significantly inhibit cell viability only at high doses (100 mg/L). Larger NP particles (500 nm and 1000 nm) resulted in a massive release of lactate dehydrogenase (LDH) from the cell (cell membrane damage). Reactive oxygen species (ROS), superoxide dismutase (SOD) and CAT tests suggest that NPs disturbed the cellular antioxidant system. 20 nm NPs show great strength in oxidizing lipids and disrupting mitochondrial function compared to NPs of other particle sizes. The degree of inhibition of CAT activity by different sized NPs was coherent at the cellular and molecular levels, and NP-500 had the most impact. This suggests that the structure and microenvironment of the polypeptide chain in the vicinity of the CAT active site is more susceptible to proximity and alteration by NP-500. In addition, the smaller NPs are capable of inducing relaxation of CAT backbone, disruption of H-bonding and reduction of α-helix content, whereas the larger NPs cause contraction of CAT backbone and increase in α-helix content. All NPs induce CAT fluorescence sensitization and make the chromophore microenvironment hydrophobic. This study provides new insights for NP risk assessment and applications.
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Catalasa , Hepatocitos , Tamaño de la Partícula , Especies Reactivas de Oxígeno , Animales , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Ratones , Especies Reactivas de Oxígeno/metabolismo , Catalasa/metabolismo , Nanopartículas/toxicidad , Supervivencia Celular/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Microplásticos/toxicidadRESUMEN
Sulfur hexafluoride (SF6) is a potent greenhouse gas. Here we use long-term atmospheric observations to determine SF6 emissions from China between 2011 and 2021, which are used to evaluate the Chinese national SF6 emission inventory and to better understand the global SF6 budget. SF6 emissions in China substantially increased from 2.6 (2.3-2.7, 68% uncertainty) Gg yr-1 in 2011 to 5.1 (4.8-5.4) Gg yr-1 in 2021. The increase from China is larger than the global total emissions rise, implying that it has offset falling emissions from other countries. Emissions in the less-populated western regions of China, which have potentially not been well quantified in previous measurement-based estimates, contribute significantly to the national SF6 emissions, likely due to substantial power generation and transmission in that area. The CO2-eq emissions of SF6 in China in 2021 were 125 (117-132) million tonnes (Mt), comparable to the national total CO2 emissions of several countries such as the Netherlands or Nigeria. The increasing SF6 emissions offset some of the CO2 reductions achieved through transitioning to renewable energy in the power industry, and might hinder progress towards achieving China's goal of carbon neutrality by 2060 if no concrete control measures are implemented.
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Due to the widespread presence of nanoplastics (NPs) in daily essentials and drinking water, the potential adverse effects of NPs on human health have become a global concern. Human serum albumin (HSA), the most abundant and multi-functional protein in plasma, has been chosen to understand the biological effects of NPs after entering the blood. The esterase activity and the transport of bisphenol A in the presence of polystyrene nanoplastics (PSNPs) under physiological conditions (pH 4.0 and 7.4) have been investigated to evaluate the possible biological effects. The interactions between PSNPs and HSA have also been systematically studied by multispectral methods and dynamic light scattering techniques. The esterase activity of HSA presented a decreased trend with increasing PSNPs; conversely, higher permeabilities are accompanied by higher amounts of PSNPs. Compared with the unchanged hydrodynamic diameter and weaker interactions at pH 7.4, stronger binding between HSA and PSNPs at pH 4.0 led to a significant increase in the particle size of the PSNPs-HSA complex. The quenching mechanism belonged to the static quenching type. The electrostatic force is proposed to be the dominant factor for PSNPs binding to HSA. The work provides some information about the toxicity of NPs when exposed to humans.
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Poliestirenos , Albúmina Sérica Humana , Humanos , Microplásticos , Dispersión Dinámica de Luz , EsterasasRESUMEN
Collagen and hyaluronic acid are commonly applied in cartilage tissue engineering, yet there has been limited investigation into their inflammatory response, a crucial factor in articular cartilage repair. This study aimed to evaluate the impact of components and physical properties of hydrogels on inflammatory response and cartilage repair. Three kinds of hydrogels with comparable storage moduli at low frequencies were designed and fabricated, namely, methacrylic anhydride-modified hyaluronic acid hydrogel (HAMA), methacrylic anhydride-modified type I collagen hydrogel (CMA) and unmodified type I collagen hydrogel (Col). HAMA hydrogel was unfavorable for adhesion and spreading of BMSCs. Furthermore, HAMA hydrogel stimulated rapid migration and pro-inflammatory M1 polarization of macrophages, leading to persistent and intense inflammation, which was unfavorable for cartilage repair. CMA and Col hydrogels possessed the same component and facilitated the adhesion, spreading and proliferation of BMSCs. Compared with CMA hydrogel, Col hydrogel induced rapid migration and moderate M1 polarization of macrophages at the early stage of injury, which was mainly influenced by its fast dissolution rate, small pore size fiber network structure and rapid stress relaxation. In addition, the phenotype of macrophages timely transformed into anti-inflammatory M2 due to the properties of the collagen component, which shortened the duration of inflammation and enhanced cartilage repair. The results indicated that moderate macrophage activation adjusted by hydrogel components and physical properties was critical in modulating inflammation and cartilage regeneration.
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Cartílago Articular , Hidrogeles , Humanos , Hidrogeles/farmacología , Hidrogeles/química , Condrocitos , Ácido Hialurónico/farmacología , Ácido Hialurónico/química , Colágeno Tipo I , Colágeno/química , Inflamación/tratamiento farmacológico , AnhídridosRESUMEN
Podocyte injury is linked to the pathogenesis and progression of renal disease. The Transcription Factor EB (TFEB), a master regulator of the autophagy and lysosomal pathways, has been found to exert cell- and tissue-specific biological function. To explore TFEB function and underlying mechanisms in podocytes, a total of 4645 differentially expressed genes (DEGs) were detected in TFEB-knockdown mouse podocytes by transcriptome sequencing. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Ingenuity Pathway Analysis showed that, apart from the enrichment in autophagy and lysosomal pathways, DEGs were enriched in cytoskeleton structure (Actin Cytoskeleton, Focal Adhesion, and Adherens Junction), as well as cytoskeleton regulatory molecular signaling (Hippo and Rho GTPase Signaling). In vitro, TFEB knockdown resulted in podocyte cytoskeletal rearrangement, which was disorganized with cortical distribution of actin filaments. Further, TFEB knockdown decreased mRNA and protein levels of Synaptopodin and led to the rearrangement of Synaptopodin. Inhibition of TFEB decreased mRNA levels for proteins involved in actin cytoskeleton dynamics. Moreover, apoptosis was increased by TFEB knockdown in podocyte. In summary, this study initiated a comprehensive analysis of the role of TFEB in podocyte function and the potential underlying mechanisms, and identified a novel role for TFEB in regulation of the podocyte actin cytoskeleton.
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Dental caries is the most common human disease caused by oral biofilms despite the widespread use of fluoride as the primary anticaries agent. Recently, an FDA-approved iron oxide nanoparticle (ferumoxytol, Fer) has shown to kill and degrade caries-causing biofilms through catalytic activation of hydrogen peroxide. However, Fer cannot interfere with enamel acid demineralization. Here, we show notable synergy when Fer is combined with stannous fluoride (SnF2), markedly inhibiting both biofilm accumulation and enamel damage more effectively than either alone. Unexpectedly, we discover that the stability of SnF2 is enhanced when mixed with Fer in aqueous solutions while increasing catalytic activity of Fer without any additives. Notably, Fer in combination with SnF2 is exceptionally effective in controlling dental caries in vivo, even at four times lower concentrations, without adverse effects on host tissues or oral microbiome. Our results reveal a potent therapeutic synergism using approved agents while providing facile SnF2 stabilization, to prevent a widespread oral disease with reduced fluoride exposure.
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Caries Dental , Fluoruros de Estaño , Humanos , Fluoruros de Estaño/farmacología , Fluoruros de Estaño/uso terapéutico , Fluoruros/farmacología , Caries Dental/prevención & control , Biopelículas , Fluoruro de Sodio/farmacologíaRESUMEN
Using a combination of spectroscopy, we devised an integrated structural strategy to comprehensively profile the molecular details of the impact of differently functionalized (plain, aminated, and carboxylated) polystyrene nanoparticles (PSNPs) on human serum albumin (HSA). The binding isotherms obtained from fluorescence and UV-vis absorption measurements demonstrate that surface functionalization can distinguish the interaction of PSNPs with HSA. Three-dimensional fluorescence and circular dichroism analysis of the effect of interaction with PSNPs on the native conformation and secondary structures of the protein reveals a diminution in the skeleton structure of HSA induced by the PSNPs. In accordance with this, it is discovered that the esterase activity of protein-PSNPs aggregates is diminished compared to that of the native protein. The carboxylated PSNPs exhibited the strongest protein binding and perturbation effects compared to other particles. Plain PSNPs exhibited significant hydrophobic interaction properties, as evidenced by spectral blue shifts and a diminished Stokes shift in the three-dimensional fluorescence assay. Our results exclusively highlight that the hydrophobic and surface charge characteristics of PSNPs govern the extent of interaction with the protein, which is beneficial to understanding microplastic toxicology.