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Integrating immunotherapy with nanomaterials-based chemotherapy presents a promising avenue for amplifying antitumor outcomes. Nevertheless, the suppressive tumor immune microenvironment (TIME) and the upregulation of cyclooxygenase-2 (COX-2) induced by chemotherapy can hinder the efficacy of the chemoimmunotherapy. This study presents a TIME-reshaping strategy by developing a steric-hindrance effect tuned zinc-based metal-organic framework (MOF), designated as CZFNPs. This nanoreactor is engineered by in situ loading of the COX-2 inhibitor, C-phycocyanin (CPC), into the framework building blocks, while simultaneously weakening the stability of the MOF. Consequently, CZFNPs achieve rapid pH-responsive release of zinc ions (Zn2+) and CPC upon specific transport to tumor cells overexpressing folate receptors. Accordingly, Zn2+ can induce reactive oxygen species (ROS)-mediated cytotoxicity therapy while synchronize with mitochondrial DNA (mtDNA) release, which stimulates mtDNA/cGAS-STING pathway-mediated innate immunity. The CPC suppresses the chemotherapy-induced overexpression of COX-2, thus cooperatively reprogramming the suppressive TIME and boosting the antitumor immune response. In xenograft tumor models, the CZFNPs system effectively modulates STING and COX-2 expression, converting "cold" tumors into "hot" tumors, thereby resulting in ≈ 4-fold tumor regression relative to ZIF-8 treatment alone. This approach offers a potent strategy for enhancing the efficacy of combined nanomaterial-based chemotherapy and immunotherapy.
Assuntos
Inibidores de Ciclo-Oxigenase 2 , Ciclo-Oxigenase 2 , Imunoterapia , Proteínas de Membrana , Estruturas Metalorgânicas , Animais , Imunoterapia/métodos , Ciclo-Oxigenase 2/metabolismo , Humanos , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Proteínas de Membrana/metabolismo , Linhagem Celular Tumoral , Camundongos , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Camundongos Endogâmicos BALB C , Espécies Reativas de Oxigênio/metabolismo , Nanopartículas/química , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Feminino , Microambiente Tumoral/efeitos dos fármacosRESUMO
Volatile organic compounds (VOCs) represent a significant component of air pollution. However, studies evaluating the impact of VOC exposure on chronic obstructive pulmonary disease (COPD) have predominantly focused on single pollutant models. This study aims to comprehensively assess the relationship between multiple VOC exposures and COPD. A large cross-sectional study was conducted on 4983 participants from the National Health and Nutrition Examination Survey. Four models, including weighted logistic regression, restricted cubic splines (RCS), weighted quantile sum regression (WQS), and the dual-pollution model, were used to explore the association between blood VOC levels and the prevalence of COPD in the U.S. general population. Additionally, six machine learning algorithms were employed to develop a predictive model for COPD risk, with the model's predictive capacity assessed using the area under the curve (AUC) indices. Elevated blood concentrations of benzene, toluene, ortho-xylene, and para-xylene were significantly associated with the incidence of COPD. RCS analysis further revealed a non-linear and non-monotonic relationship between blood levels of toluene and m-p-xylene with COPD prevalence. WQS regression indicated that different VOCs had varying effects on COPD, with benzene and ortho-xylene having the greatest weights. Among the six models, the Extreme Gradient Boosting (XGBoost) model demonstrated the strongest predictive power, with an AUC value of 0.781. Increased blood concentrations of benzene and toluene are significantly correlated with a higher prevalence of COPD in the U.S. population, demonstrating a non-linear relationship. Exposure to environmental VOCs may represent a new risk factor in the etiology of COPD.
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Inquéritos Nutricionais , Doença Pulmonar Obstrutiva Crônica , Compostos Orgânicos Voláteis , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/sangue , Humanos , Compostos Orgânicos Voláteis/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Idoso , Estados Unidos/epidemiologia , Adulto , Prevalência , Poluentes Atmosféricos/sangue , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Exposição Ambiental/efeitos adversos , Fatores de RiscoRESUMO
The risk of harmful microorganisms to ecosystems and human health has stimulated exploration of singlet oxygen (1O2)-based disinfection. It can be potentially generated via an electrocatalytic process, but is limited by the low production yield and unclear intermediate-mediated mechanism. Herein, we designed a two-site catalyst (Fe/Mo-N/C) for the selective 1O2 generation. The Mo sites enhance the generation of 1O2 precursors (H2O2), accompanied by the generation of intermediate â¢HO2/â¢O2-. The Fe site facilitates activation of H2O2 into â¢OH, which accelerates the â¢HO2/â¢O2- into 1O2. A possible mechanism for promoting 1O2 production through the ROS-mediated chain reaction is reported. The as-developed electrochemical disinfection system can kill 1 × 107 CFU mL-1 of E. coli within 8 min, leading to cell membrane damage and DNA degradation. It can be effectively applied for the disinfection of medical wastewater. This work provides a general strategy for promoting the production of 1O2 through electrocatalysis and for efficient electrochemical disinfection.
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Desinfecção , Escherichia coli , Peróxido de Hidrogênio , Oxirredução , Oxigênio Singlete , Oxigênio Singlete/química , Oxigênio Singlete/metabolismo , Desinfecção/métodos , Catálise , Escherichia coli/metabolismo , Peróxido de Hidrogênio/química , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/química , Técnicas Eletroquímicas , Molibdênio/química , Ferro/química , Águas Residuárias/química , Águas Residuárias/microbiologiaRESUMO
Inaccurate or cumbersome clinical pathogen diagnosis between Gram-positive bacteria (G+) and Gram-negative (G-) bacteria lead to delayed clinical therapeutic interventions. Microelectrode-based electrochemical sensors exhibit the significant advantages of rapid response and minimal sample consumption, but the loading capacity and discrimination precision are weak. Herein, we develop reversible fusion-fission MXene-based fiber microelectrodes for G+/G- bacteria analysis. During the fissuring process, the spatial utilization, loading capacity, sensitivity, and selectivity of microelectrodes were maximized, and polymyxin B and vancomycin were assembled for G+/G- identification. The surface-tension-driven reversible fusion facilitated its reusability. A deep learning model was further applied for the electrochemical impedance spectroscopy (EIS) identification in diverse ratio concentrations of G+ and G- of (1:100-100:1) with higher accuracy (>93%) and gave predictable detection results for unknown samples. Meanwhile, the as-proposed sensing platform reached higher sensitivity toward E. coli (24.3 CFU/mL) and S. aureus (37.2 CFU/mL) in 20 min. The as-proposed platform provides valuable insights for bacterium discrimination and quantification.
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Microeletrodos , Bactérias Gram-Positivas/isolamento & purificação , Bactérias Gram-Negativas/isolamento & purificação , Escherichia coli/isolamento & purificação , Staphylococcus aureus/isolamento & purificação , Técnicas Eletroquímicas/instrumentação , Vancomicina/farmacologia , Antibacterianos/farmacologia , Antibacterianos/análise , Polimixina B/química , Polimixina B/farmacologia , Espectroscopia DielétricaRESUMO
Singlet oxygen (1 O2 ) plays a significant role in environmental and biomedical disinfection fields. Electrocatalytic processes hold great potential for 1 O2 generation, but remain challenging. Herein, a facile Ni doping converted spin-state transition approach is reported for boosting 1 O2 production. Magnetic analysis and theoretical calculations reveal that Ni occupied at the octahedral site of Co3 O4 can effectively induce a low-to-high spin-state transition. The high-spin Ni-Co3 O4 generate appropriate binding strength and enhance electron transfer between the Co centers with oxygen intermediates, thereby improving the catalytic activity of Ni-Co3 O4 for effective generating 1 O2 . In neutral conditions, 1×106 â CFU mL-1 Gram-negative ESBL-producing Escherichia coli (E. coli) could be inactivated by Ni-Co3 O4 system within 5â min. Further antibacterial mechanisms indicate that 1 O2 can lead to cell membrane damage and DNA degradation so as to irreversible cell death. Additionally, the developed Ni-Co3 O4 system can effectively inactivate bacteria from wastewater and bioaerosols. This work provides an effective strategy for designing high-spin electrocatalysis to boost 1 O2 generation for disinfection process.
Assuntos
Desinfecção , Oxigênio Singlete , Escherichia coli , Hibridização de Ácido Nucleico , Hibridização Genética , OxigênioRESUMO
Antibacterial nanomaterials provide promising alternative strategies to combat the bacterial infection due to deteriorating resistance. However, few have been practically applied due to the lack of clear antibacterial mechanisms. In this work, we selected good-biocompatibility iron-doped CDs (Fe-CDs) with antibacterial activity as a comprehensive research model to systematically reveal the intrinsic antibacterial mechanism. Through energy dispersive spectroscopy (EDS) mapping of in situ ultrathin sections of bacteria, we found that a large amount of iron was accumulated inside the bacteria treated with Fe-CDs. Then, combining the data of cell level and transcriptomics, it can be elucidated that Fe-CDs could interact with cell membranes, enter bacterial cells through iron transport and infiltration, increase intracellular iron levels, trigger increased reactive oxygen species (ROS), and lead to disruption of Glutathione (GSH)-dependent antioxidant mechanisms. Excessive ROS further leads to lipid peroxidation and DNA damage in cells, lipid peroxidation destroys the integrity of the cell membrane, and finally leads to the leakage of intracellular substances resulting in bacterial growth inhibition and death. This result provides important insights into the antibacterial mechanism of Fe-CDs and further provides a basis for the deep application of nanomaterials in biomedicine.
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Nanoestruturas , Pontos Quânticos , Ferro/química , Carbono/farmacologia , Carbono/química , Espécies Reativas de Oxigênio , Antibacterianos/farmacologia , Antibacterianos/química , Pontos Quânticos/químicaRESUMO
On accounts of the advantages of inherent high stability, ease of preparation and superior catalytic activities, nanozymes have attracted tremendous potential in diverse biomedical applications as alternatives to natural enzymes. Optimizing the activity of nanozymes is significant for widening and boosting the applications into practical level. As the research of the catalytic activity regulation strategies of nanozymes is boosting, it is essential to timely review, summarize, and analyze the advances in structure-activity relationships for further inspiring ingenious research into this prosperous area. Herein, the activity regulation methods of nanozymes in the recent 5 years are systematically summarized, including size and morphology, doping, vacancy, surface modification, and hybridization, followed by a discussion of the latest biomedical applications consisting of biosensing, antibacterial, and tumor therapy. Finally, the challenges and opportunities in this rapidly developing field is presented for inspiring more and more research into this infant yet promising area.
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Nanoestruturas , Humanos , Catálise , Hibridização de Ácido Nucleico , Relação Estrutura-AtividadeRESUMO
We present multiPrime, a novel tool that automatically designs minimal primer sets for targeted next-generation sequencing, tailored to specific microbiomes or genes. MultiPrime enhances primer coverage by designing primers with mismatch tolerance and ensures both high compatibility and specificity. We evaluated the performance of multiPrime using a data set of 43,016 sequences from eight viruses. Our results demonstrated that multiPrime outperformed conventional tools, and the primer set designed by multiPrime successfully amplified the target amplicons. Furthermore, we expanded the application of multiPrime to 30 types of viruses and validated the work efficacy of multiPrime-designed primers in 80 clinical specimens. The subsequent sequencing outcomes from these primers indicated a sensitivity of 94% and a specificity of 89%.
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Photocatalysis under mild conditions is an intriguing avenue for organic chemical manufacturing to confront the serious fossil energy crisis. Herein, we report a direct light-driven alkene production through alcohol dehydration, using nonstoichiometric tungsten oxide of W18O49 nanowires with abundant lattice defects as a photocatalyst. A representative ethylene (C2H4) production rate of 275.5 mmol gcat -1 h-1 is achieved from ethanol (C2H5OH) dehydration, together with excellent selectivity up to 99.9%. The universality of our approach is further demonstrated with other alcohol dehydration. Combining ultrafast transient absorption spectroscopy with in situ X-ray photoelectron spectroscopy, we underline that the inter- and intraband transitions synergistically contribute to such excellent activity. In particular, the intraband transition excites the electrons in defect bands into an energetically "hot" state, largely alleviating the charge recombination. As a result, the C-OH bond of chemisorbed C2H5OH molecules can be effectively dissociated to furnish the formation of C=C bonds. Our work offers a fresh insight into sustainable alkene production with renewable energy input under mild conditions.
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Owing to the easy over-oxidation, it is a promising yet challenging task to explore renewable carbon resources to control the sunlight-driven selective catalytic oxidation of biomass-derived 5-hydroxymethylfurfural (HMF), producing important chemical feedstocks, namely, less-oxidized 2,5-diformylfuran (DFF) and 5-hydroxymethyl-2-furancarboxylic acid (HMFCA). Herein, we have developed a photocatalyst by anchoring a Ru complex on CdS quantum dots, which achieves selective oxidation of HMF toward DFF or HMFCA with high conversion (>81 %) and selectivity (>90 %), based on the controllable generation of two oxygen radicals under different atmospheres. Such selective conversion can also work well outside the laboratory by using natural sunlight. In particular, the selective production of HMFCA through photocatalytic HMF oxidation is achieved for the first time. More importantly, our photocatalyst is applicable for the selective oxidation of other compounds with hydroxyl and aldehyde groups.
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Furanos , Luz Solar , Ácidos , Catálise , Furaldeído/análogos & derivados , Furaldeído/química , Furanos/químicaRESUMO
OBJECTIVES: To study the molecular epidemiological characteristics of norovirus in children with acute gastroenteritis from 2017 to 2019. METHODS: A retrospective analysis was performed on the medical data of children with acute gastroenteritis who were admitted to Children's Hospital of Chongqing Medical University from January 2017 to December 2019. A total of 1 458 stool samples were collected from the children, and viral RNA was extracted. Reverse transcription polymerase chain reaction was used for gene amplification, sequencing, and genotype identification of the VP1 region of capsid protein in norovirus. RESULTS: Among the 1 458 stool samples, 158 (10.8%) were positive for norovirus. There was no significant difference in the positive detection rate of norovirus between different years (P>0.05). Boys had a norovirus detection rate of 12.2% (105/860), which was significantly higher than that in girls (8.9%, 53/598) (P=0.043). The children aged 12 to <18 months had the highest norovirus detection rate (16.9%, 51/301). August, September, and October were the epidemic peak season. A total of 23 norovirus-positive samples were also positive for rotavirus. The norovirus detected were mainly GII type (97.5%, 154/158), and only 4 cases were GI type (2.5%, 4/158). The sequencing of the VP1 region of capsid protein in the positive samples showed that GII.4 (69.6%, 110/158) was the dominant genotype, among which 99 (62.7%, 99/158) were GII.4 Sydney 2012, followed by GII.3 (15.2%, 24/158), GII.2 (10.1%, 16/158), GII.6 (1.9%, 3/158), and GII.17 (0.6%, 1/158). GI.3 (1.3%, 2/158), GI.2 (0.6%, 1/158), and GI.5 (0.6%, 1/158) were rarely detected. CONCLUSIONS: Norovirus GII.4 Sydney 2012 was the major epidemic strain in the children with norovirus gastroenteritis from 2017 to 2019. Although norovirus infection can exist throughout the year, August to October is the peak period. During this period, norovirus surveillance and key population protection are strengthened to help prevent and control norovirus diarrhea.
Assuntos
Gastroenterite , Norovirus , Criança , Fezes , Feminino , Gastroenterite/epidemiologia , Humanos , Masculino , Norovirus/genética , Filogenia , Estudos RetrospectivosRESUMO
The design of efficient and stable photocatalysts for robust CO2 reduction without sacrifice reagent or extra photosensitizer is still challenging. Herein, a single-atom catalyst of isolated single atom cobalt incorporated into Bi3O4Br atomic layers is successfully prepared. The cobalt single atoms in the Bi3O4Br favors the charge transition, carrier separation, CO2 adsorption and activation. It can lower the CO2 activation energy barrier through stabilizing the COOH* intermediates and tune the rate-limiting step from the formation of adsorbed intermediate COOH* to be CO* desorption. Taking advantage of cobalt single atoms and two-dimensional ultrathin Bi3O4Br atomic layers, the optimized catalyst can perform light-driven CO2 reduction with a selective CO formation rate of 107.1 µmol g-1 h-1, roughly 4 and 32 times higher than that of atomic layer Bi3O4Br and bulk Bi3O4Br, respectively.
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Solar-driven reduction of CO2 , which converts inexhaustible solar energy into value-added fuels, has been recognized as a promising sustainable energy conversion technology. However, the overall conversion efficiency is significantly limited by the inefficient charge separation and sluggish interfacial reaction dynamics, which resulted from a lack of sufficient active sites. Herein, Bi12 O17 Cl2 superfine nanotubes with a bilayer thickness of the tube wall are designed to achieve structural distortion for the creation of surface oxygen defects, thus accelerating the carrier migration and facilitating CO2 activation. Without cocatalyst and sacrificing reagent, Bi12 O17 Cl2 nanotubes deliver high selectivity CO evolution rate of 48.6â µmol g-1 h-1 in water (16.8 times than of bulk Bi12 O17 Cl2 ), while maintaining stability even after 12â h of testing. This paves the way to design efficient photocatalysts with collaborative optimizing charge separation and CO2 activation towards CO2 photoreduction.
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BACKGROUND: Fusarium graminearum is the main pathogen of Fusarium head blight (FHB), a worldwide plant disease and a major disease of wheat in China. Control of FHB is mainly dependent on the application of demethylase inhibitor (DMI) fungicides. Fungal sterol 14α-demethylase enzymes (CYP51) are the main target for DMI fungicides. A molecular modeling study and biological evaluation were performed to investigate the binding mechanism between azoles and CYP51B in F. graminearum. RESULTS: A homology model based on the crystal structure of Aspergillus fumigatus was built. Molecular docking and molecular dynamics (MD) simulations were then used to identify the optimum binding mode of propiconazole (PRP), diniconazole (DIN), triadimenol (TRL), tebuconazole (TEC) and triadimefon (TRN) with FgCYP51B. Furthermore, the binding free energy of the five protein-inhibitor complexes was calculated using molecular mechanics generalized Born surface area and Poisson-Boltzmann surface area (MM-GB/PBSA) methods. Key residues in the selective binding of azoles to FgCYP51B were recognized by per-residue free energy decomposition analysis. The five ligands have a similar binding mode in the active pocket. The binding free energy to the enzyme for inhibitors PRP and TEC is more favorable than that of TRN, TRL and DIN. Furthermore, the amino acid residues Phe511, Val136, Ile374, Ala308, Ser312 and Try137 of FgCYP51B are key residues interacting with azoles fungicides. From the experimental evaluation, the 50% effective concentration (EC50 ) values for PRP, TEC, DIN, TRL and TRN are 0.024, 0.047, 0.148, 0.154 and 0.474 mg L-1 , respectively. These five molecules exhibit potential inhibitory activity against CYP51B protein from F. graminearum. CONCLUSION: Azole fungicides for FgCYP51B should possess more hydrophobic groups interacting with residues Phe511, Val136, Ile374, Ala308, Ser312 and Tyr137. PRP and TEC are preferable for the control of FHB than DIN, TRL and TRN. © 2017 Society of Chemical Industry.