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Toxoplasma gondii is among the most important parasites worldwide. The apicoplast is a unique organelle shared by all Apicomplexan protozoa. Increasing lines of evidence suggest that the apicoplast possesses its own ubiquitination system. Deubiquitination is a crucial step executed by deubiquitinase (DUB) during protein ubiquitination. While multiple components of ubiquitination have been identified in T. gondii, the deubiquitinases involved remain unknown. The aim of the current study was to delineate the localization of TgOTU7 and elucidate its functions. TgOTU7 was specifically localized at the apicoplast, and its expression was largely regulated during the cell cycle. Additionally, TgOTU7 efficiently breaks down ubiquitin chains, exhibits linkage-nonspecific deubiquitinating activity and is critical for the lytic cycle and apicoplast biogenesis, similar to the transcription of the apicoplast genome and the nuclear genes encoding apicoplast-targeted proteins. Taken together, the results indicate that the newly described deubiquitinase TgOTU7 specifically localizes to the apicoplast and affects the cell growth and apicoplast homeostasis of T. gondii.
Assuntos
Apicoplastos , Toxoplasma , Animais , Toxoplasma/genética , Apicoplastos/genética , Apicoplastos/metabolismo , Ciclo Celular , Homeostase , Enzimas Desubiquitinantes/genética , Enzimas Desubiquitinantes/metabolismo , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismoRESUMO
The chiral H8-BINOL derivatives R-1 and R-2 were efficiently synthesized via a Suzuki coupling reaction, and they can be used as novel dialdehyde fluorescent probes for the enantioselective recognition of R/S-2-amino-1-phenylethanol. In addition, R-1 is much more effective than R-2. Scanning electron microscope images and X-ray analyses show that R-1 can form supramolecular vesicles through the self-assembly effect of the π-π force and strong hydrogen bonding. As determined via analysis, the fluorescence of the probe was significantly enhanced by mixing a small amount of S-2-amino-1-phenylethanol into R-1, with a redshift of 38 nm, whereas no significant fluorescence response was observed in R-2-amino-1-phenylethanol. The enantioselective identification of S-2-amino-1-phenylethanol by the probe R-1 was further investigated through nuclear magnetic titration and fluorescence kinetic experiments and DFT calculations. The results showed that this mechanism was not only a simple reactive probe but also realized object recognition through an ICT mechanism. As the intramolecular hydrogen bond activated the carbonyl group on the probe R-1, the carbonyl carbon atom became positively charged. As a strong nucleophile, the amino group of S-2-amino-1-phenylethanol first transferred the amino electrons to a carbonyl carbocation, resulting in a significantly enhanced fluorescence of the probe R-1 and a 38 nm redshift. Similarly, S-2-amino-1-phenylethanol alone caused severe damage to the self-assembled vesicle structure of the probe molecule itself due to its spatial structure, which made R-1 highly enantioselective towards it.
Assuntos
Amino Álcoois , Ligação de Hidrogênio , Estereoisomerismo , Amino Álcoois/química , Corantes Fluorescentes/química , Cinética , Estrutura Molecular , Modelos Moleculares , NaftóisRESUMO
Immunotherapy has greatly changed the status of cancer treatment, and many patients do not respond or develop acquired resistance. The related research is blocked by lacking of comprehensive resources for researchers to discovery and analysis signatures, then further exploring the mechanisms. Here, we first offered a benchmarking dataset of experimentally supported signatures of cancer immunotherapy by manually curated from published literature works and provided an overview. We then developed CiTSA ( http://bio-bigdata.hrbmu.edu.cn/CiTSA/ ) which stores 878 entries of experimentally supported associations between 412 signatures such as genes, cells, and immunotherapy across 30 cancer types. CiTSA also provides flexible online tools to identify and visualize molecular/cell feature and interaction, to perform function, correlation, and survival analysis, and to execute cell clustering, cluster activity, and cell-cell communication analysis based on single cell and bulk datasets of cancer immunotherapy. In summary, we provided an overview of experimentally supported cancer immunotherapy signatures and developed CiTSA which is a comprehensive and high-quality resource and is helpful for understanding the mechanism of cancer immunity and immunotherapy, developing novel therapeutic targets and promoting precision immunotherapy for cancer.
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Neoplasias , Análise da Expressão Gênica de Célula Única , Humanos , Neoplasias/genética , Neoplasias/terapia , ImunoterapiaRESUMO
Meticulously engineered nanomaterials achieve significant advances in the diagnosis and therapy of solid tumors by improving tumor delivery efficiency; and thereby, enhancing imaging and therapeutic efficacy. Currently, polydopamine (PDA) attracts widespread attention because of its biocompatibility, simplicity of preparation, abundant surface groups, and high photothermal conversion efficiency, which can be applied in drug delivery, photothermal therapy, theranostics, and other nanomedicine fields. Inspired by PDA structures that are rich in catechol and amino functional groups that can coordinate with various metal ions, which have charming qualities and characteristics, metal-coordinated PDA structures are exploited for tumor theranostics, but are not thoroughly summarized. Herein, this review summarizes the recent progress in the fabrication of metal-coordinated PDA structures and their availabilities in tumor imaging and therapy, with further in-depth discussion of the challenges and future perspectives of metal-coordinated PDA structures, with the aim that this systematic review can promote interdisciplinary intersections and provide inspiration for the further growth and clinical translation of PDA materials.
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The study about simultaneously enhancing the resistive switching level and ambient-air-stability of perovskite-based memorizers will promote its commercialization. Here, a new 3D perovskite (TAZ-H)PbBr3 (TAZ-H+ = protonated thiazole) has been fabricated as FTO/(TAZ-H)PbBr3/Ag device, which only exhibits binary memory performance with the high tolerant temperature of 170 °C. After encapsulating by polyvinylpyrrolidone (PVP), the (TAZ-H)PbBr3@PVP composite-based device can demonstrate ternary resistive switching behavior with considerable ON2/ON1/OFF ratio (105.9: 103.9:1) and high ternary yield (68 %). Specially, this device presents good ambient-air stability at RH 80 % and thermal tolerance of 100 °C. The binary resistive switching mechanism can be ascribed to the halogen ion migration induced by bromine defects in the (PbBr3)nn- framework. But the ternary resistive switching phenomenon in the (TAZ-H)PbBr3@PVP-based device could be depicted as the carrier transport from filled traps of PVP to (PbBr3)nn- framework (ON1 state) and then carriers flowing in the re-arranged (TAZ-H)nn+ chain in 3D channels (ON2 state). The PVP treatment can not only modify the grain boundary defects, but also facilitate the transport of injected carriers to the perovskite films via Pb-O coordinated bonds and inhibition of order-disorder transformation. This facial strategy for implementing ternary perovskite-based memorizers with good ambient-air-stability is quite meaningful for high-density memory in harsh environments.
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After harvest, the metabolism of Gynura bicolor DC (G. bicolor) is vigorous, resulting in sugar scarcity and reactive oxygen species (ROS) accumulation, thus aggravating the quality deterioration. 1-Methylcyclopropene (1-MCP) shows crucial effect in alleviating the postharvest metabolism of vegetables and fruits. This research aimed to evaluate the effect of 1-MCP on ROS scavenging and sucrose metabolism in G. bicolor. In this research, G. bicolor was treated with 10 µL L-1 1-MCP for 12 h, followed by storage at 20 ± 2 °C and 90 ± 5% relative humidity in darkness for 7 days. During storage, the increases in the respiration rate, electrolytic leakage, weight loss rate, ROS levels, and membrane lipid oxidation were effectively inhibited by 1-MCP. Moreover, starch and hexose degradation was decreased in the 1-MCP group, as were sucrose synthesis and catabolism. Correlation analysis indicated that sugar starvation was associated with respiration, activities regulation of CAT, SOD, and enzymes involved in sucrose metabolism were associated with the levels of hydrogen peroxide at the early storage. In conclusion, 1-MCP delayed postharvest quality deterioration of G. bicolor by alleviating respiration, inducing oxidative stress to enhance ROS scavenging, and inhibiting sucrose metabolism.
Assuntos
Ciclopropanos , Açúcares , Ciclopropanos/farmacologia , Frutas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sacarose/farmacologia , Açúcares/farmacologia , Asteraceae/metabolismoRESUMO
Simulating the adsorption behavior of Sb(V) on goethite is of great significance for predicting the mobility of Sb(V) in soil. However, there is still a lack of charge distribution and multisite surface complexation (CD-MUSIC) models that conform to the actual adsorption mechanism. Therefore, our research combined the previous EXAFS results with the SCMs and established two CD-MUSIC models (Model I, which introduced bidentate binuclear and bidentate mononuclear complexes, and Model II, which introduced bidentate mononuclear and monodentate mononuclear complexes). It is also one of the rare cases that bidentate edge- and corner-sharing adsorption complexes have been distinguished by introducing different amounts of H+. The results showed that Model I was more suitable for predicting the adsorption behavior of Sb(V) on the goethite surface than Model II. However, at low pH and high Sb(V) loading, the presence of the monodentate complex ≡FeOHSb(OH)50.5- was possible due to the fast and slow two-step mechanism. Using the optimized CD-MUSIC model parameters, the contribution of surface species to the equilibrium adsorption under different conditions was determined. In the adsorption edge and adsorption isotherm simulation process, the edge-sharing bidentate mononuclear complex ≡(FeO)2H2Sb(OH)4 was always the most important product, which was consistent with the results of extended X-ray absorption fine structure (EXAFS) analysis. The applicability of the model parameters was verified by predicting the competitive adsorption between PO43- and Sb(V). The CD-MUSIC model established in the present study could be a useful tool for evaluating the equilibrium distribution behavior and environmental risk of Sb(V) in different types of soils.
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The aim of this study was to investigate the effects of feedstock material and pyrolysis temperature on the content and spectral properties of dissolved organic matter(DOM) in biochars. Biochars were produced from the pyrolysis of rice straw and Cunninghamia lanceolata litter at three temperatures(350, 500, and 650â). The results showed that the pH values of the two biochars with pyrolysis temperature increases were improved from 8.10 and 6.56 to 10.53 and 8.23, respectively. The pyrolysis temperature had no significant effect on the total C content of biochar, but the feedstock material and their interaction had significant effects on the total C content of the biochar(P<0.05). The dissolved organic carbon(DOC) content of the two types of biochar first decreased and then increased with increasing pyrolysis temperature, and the content of DOC of the biochar derived from rice straw was significantly higher than that from Cunninghamia lanceolata litter under the same temperature(P<0.05). The feedstock material had no significant effect on the SUVA254 value of DOM, but temperature and its interactive effect with the feedstock material had a significant effect on the SUVA254 values(P<0.05). Maximum DOC SUVA254 values occurred at 500â in the two types of biochar, indicating the highest degree of aromatization. Three-dimensional fluorescence spectra showed that the DOM components of the two types of biochar were dominated by fulvic acid-like and humic acid-like material, which had different responses to pyrolysis temperature. FTIR spectra suggested that the DOM of the biochars had absorption peaks at similar positions, in five regions, and the stretching vibration of aliphatic C-H gradually weakened with an increase in pyrolysis temperature. Therefore, the biochars produced at higher pyrolysis temperatures(500â and 650â) had lower DOC contents but a higher aromatization degree and humification degree, and were more stable, compared to the biochars produced at a lower pyrolysis temperature(350â).
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Carvão Vegetal , Pirólise , Substâncias Húmicas/análise , TemperaturaRESUMO
Tumorigenesis is associated with metabolic abnormalities and genomic instability. Microsatellite mutations, including microsatellite instability (MSI) and loss of heterozygosity (LOH), are associated with the functional impairment of some tumor-related genes. To investigate the role of MSI and LOH in sporadic breast tumors in canines, 22 tumors DNA samples and their adjacent normal tissues were evaluated using polyacrylamide gel electrophoresis and silver staining for 58 microsatellites. Quantitative real-time polymerase chain reaction, promoter methylation analysis and immunohistochemical staining were used to quantify gene expression. The results revealed that a total of 14 tumors (6 benign tumors and 8 breast cancers) exhibited instability as MSI-Low tumors. Most of the microsatellite loci possessed a single occurrence of mutations. The maximum number of MSI mutations on loci was observed in tumors with a lower degree of differentiation. Among the unstable markers, FH2060 (4/22), ABCC9tetra (4/22) and SCN11A (6/22) were high-frequency mutation sites, whereas FH2060 was a high-frequency LOH site (4/22). The ABCC9tetra locus was mutated only in cancerous tissue, although it was excluded by transcription. The corresponding genes and proteins were significantly downregulated in malignant tissues, particularly in tumors with MSI. Furthermore, the promoter methylation results of the adenosine triphosphate binding cassette subfamily C member 9 (ABCC9) showed that there was a high level of methylation in breast tissues, but only one case showed a significant elevation compared with the control. In conclusion, MSI-Low or MSI-Stable is characteristic of most sporadic mammary tumors. Genes associated with tumorigenesis are more likely to develop MSI. ABCC9 protein and transcription abnormalities may be associated with ABCC9tetra instability.
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The development of new high-density memories that can work in harsh environments such as high temperature and humidity will be significant for some special occasions such as oil and geothermal industries. Herein, a facial strategy for implementing a ternary memory device with high working temperature/humidity was executed. In detail, an asymmetric aggregation-induced-emission active molecule (azobenzol-decorated tetraphenylethylene, i.e., TPE-Azo) was embedded into flexible poly(ethylene-alt-maleic anhydride) (PEM) to prepare a TPE-Azo@PEM composite, which served as an active layer to fabricate the FTO/TPE-Azo@PEM/Ag device. This device can demonstrate excellent ternary memory performances with a current ratio of 1:104.2:101.6 for "OFF", "ON1", and "ON2" states. Specially, it can exhibit good environmental endurance at high working temperature (350 °C) and humidity (RH = 90%). The ternary memory mechanism can be explained as the combination of aggregation-induced current/conductance and conformational change-induced charge transfer in the TPE-Azo molecule, which was verified by Kelvin probe force microscopy, UV-vis spectra, X-ray diffraction, and single-crystal structural analysis. This strategy can be used as a universal method for the construction of high-density multilevel memristors with good environmental tolerance.
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Electrically bistable devices play an important role in the next generation of information materials. Plasmonic noble metal nanoparticles (Au and Ag NPs) with diameters <6 nm were embedded into 3-D Cd-based metal-organic framework (MOF) matrixes via the photoreduction method to generate Au (Ag) NPs@MOF composites. Electrical bistability measurements on the sandwiched ITO/NPs@MOF/silver devices indicate that two switchable conductivity states with nonvolatile memory behaviors can be observed. The ITO/Au NP@2/Ag device with neutral matrix possesses the highest ON/OFF current ratio of 104, which can be attributed to its higher electron tunneling efficiency because of the better dispersity of Au NPs in the MOF matrix. A mechanism regarding the electric-field-induced charge-transfer process assisted by conformational change in the active layer was proposed.