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Protein-based detection methods, enzyme-linked immunosorbent assays (ELISAs) and lateral flow strips, have been widely used for rapid, specific, and sensitive detection of genetically modified organisms (GMOs). However, the traditional ELISA method for the quantitative detection of GMOs has certain limitations. Herein, a quantum dot (QD)-based fluorescence-linked immunosorbent assay was developed using QDs as fluorescent markers for the detection of glyphosate-resistant protein (CP4-EPSPS) in the MON89788 soybean. The end-point fluorescent detection system was carried out using QDs conjugated with a goat anti-rabbit secondary antibody. Compared with the conventional sandwich ELISA method, the newly developed fluorescence-linked immunosorbent assay was highly sensitive and accurate for detecting the CP4-EPSPS protein. The quantified linearity was achieved in the range of 0.05-5% (w/w) for the MON89788 soybean sample. The recovery of protein extracted from mixed MON89788 soybean samples ranged from 87.67% to 116.83%. The limits of detection and limits of quantification were 0.7101 and 2.152 pg/mL, respectively. All of the results indicated that the QD-based fluorescence-linked immunosorbent assay was a highly specific and sensitive method for monitoring the CP4-EPSPS protein in GMOs.
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Fish cells, such as grass carp (Ctenopharyngodon idella) kidney (CIK) cells, are harder to transfect than mammalian cells. There is a need for an efficient gene delivery system for fish cells. Here, we used CIK cell line as a model to develop a strategy to enhance RNA and plasmid DNA transfection efficiency using a nanocarrier generated from α-lactalbumin (α-NC). α-NC absorbed nucleic acid cargo efficiently and exhibited low cytotoxicity. Plasmid transfection was more efficient with α-NC than with liposomal transfection reagents. We used α-NC to co-transfect Tol2 transposase mRNA and a plasmid containing Cas9 and GFP, generating a stable transgenic CIK cell line. Genome and RNA sequencing revealed that the Cas9 and GFP fragments were successfully inserted into the genome of CIK cells and efficiently transcribed. In this study, we established an efficient transfection system for fish cells using α-NC, simplifying the process of generating stable transgenic fish cell lines.
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The preferable antigen delivery profile accompanied by sufficient adjuvants favors vaccine efficiency. Mitochondria, which feature prokaryotic characteristics and contain various damage-associated molecular patterns (DAMPs), are easily taken up by phagocytes and simultaneously activate innate immunity. In the current study, we established a mitochondria engineering platform for generating antigen-enriched mitochondria as cancer vaccine. Ovalbumin (OVA) and tyrosinase-related protein 2 (TRP2) were used as model antigens to synthesize fusion proteins with mitochondria-localized signal peptides. The lentiviral infection system was then employed to produce mitochondrial vaccines containing either OVA or TRP2. Engineered OVA- and TRP2-containing mitochondria (OVA-MITO and TRP2-MITO) were extracted and evaluated as potential cancer vaccines. Impressively, the engineered mitochondria vaccine demonstrated efficient antitumor effects when used as both prophylactic and therapeutic vaccines in murine tumor models. Mechanistically, OVA-MITO and TRP2-MITO potently recruited and activated dendritic cells (DCs) and induced a tumor-specific cell-mediated immunity. Moreover, DC activation by mitochondria vaccine critically involves TLR2 pathway and its lipid agonist, namely, cardiolipin derived from the mitochondrial membrane. The results demonstrated that engineered mitochondria are natively well-orchestrated carriers full of immune stimulants for antigen delivery, which could preferably target local dendritic cells and exert strong adaptive cellular immunity. This proof-of-concept study established a universal platform for vaccine construction with engineered mitochondria bearing alterable antigens for cancers as well as other diseases.
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Dysregulation of splicing factor expression plays a crucial role in the progression of hepatocellular carcinoma (HCC). Our research found that the expression level of splicing factor ZMAT2 was increased in HCC, promoting the proliferation of HCC cells. RNAseq data indicated that the absence of ZMAT2 induced skipping exon of mRNA, while RIPseq data further revealed the mRNA binding motifs of ZMAT2. A comprehensive analysis of RNAseq and RIPseq data indicateed that ZMAT2 played a crucial role in the maturation process of TRIM28 mRNA. Knocking down of ZMAT2 led to the deletion of 25 bases in exon 11 of TRIM28, ultimately resulting in nonsense-mediated decay (NMD). Our data revealed that ZMAT2 could regulate TRIM28 to reduce the accumulation of ROS in HCC cells, thereby promoting their proliferation. Our research also discovered that ZMAT2 was capable of undergoing phase separation, resulting in the formation of liquid droplet condensates within HCC cells. Additionally, it was found that ZMAT2 was able to form protein-nucleic acid condensates with TRIM28 mRNA. In summary, this study is the first to reveal that ZMAT2 and TRIM28 mRNA form protein-nucleic acid condensates, thereby regulating the splicing of TRIM28 mRNA. The increased expression of ZMAT2 in HCC leads to upregulated TRIM28 expression and reduced ROS accumulation, ultimately accelerating the proliferation of HCC cells.
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Processamento Alternativo , Carcinoma Hepatocelular , Proliferação de Células , Neoplasias Hepáticas , Espécies Reativas de Oxigênio , Proteína 28 com Motivo Tripartido , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Proliferação de Células/genética , Espécies Reativas de Oxigênio/metabolismo , Processamento Alternativo/genética , Proteína 28 com Motivo Tripartido/metabolismo , Proteína 28 com Motivo Tripartido/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genéticaRESUMO
Importance: Little is known about the risk of suicidal behavior in relation to having a spouse with a cancer diagnosis. Objective: To estimate the risk of suicide attempt and suicide death among spouses of patients with cancer. Design, Setting, and Participants: This nationwide cohort study in Denmark collected registry-based data from 1986 through 2016. Analyses were performed from August 8, 2022, to October 30, 2023. Individuals who had a spouse with a cancer diagnosed during 1986 to 2015 were compared with individuals whose spouse did not have a cancer diagnosis during the same period, randomly selected from the general population and matched by birth year and sex. Exposure: Having a spouse with a cancer diagnosis. Main Outcomes and Measures: Suicide attempt was identified through the Danish National Patient Register and the Danish Psychiatric Central Research Register, whereas suicide death was identified through the Danish Causes of Death Register, through 2016. Flexible parametric and Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for suicide attempt and suicide death among spouses of patients with a cancer diagnosis. Results: The study included 409â¯338 exposed individuals and 2â¯046â¯682 unexposed individuals (median [IQR] age at cohort entry for both groups, 63 [54-70] years; 55.4% women). During the follow-up, 2714 incident cases of suicide attempt among exposed individuals (incidence rate [IR], 62.6 per 100â¯000 person-years) and 9994 among unexposed individuals (IR, 50.5 per 100â¯000 person-years) were identified, as well as 711 cases of suicide death among the exposed individuals (IR, 16.3 per 100â¯000 person-years) and 2270 among the unexposed individuals (IR, 11.4 per 100â¯000 person-years). An increased risk of suicide attempt (HR, 1.28; 95% CI, 1.23-1.34) and suicide death (HR, 1.47; 95% CI, 1.35-1.60) was observed among spouses of patients with cancer throughout the follow-up. The increased risk was particularly notable during the first year after the cancer diagnosis, with an HR of 1.45 (95% CI, 1.27-1.66) for suicide attempt and 2.56 (95% CI, 2.03-3.22) for suicide death. There was a greater risk increase for both suicide attempt and suicide death when the cancer was diagnosed at an advanced stage or when the spouse died after the cancer diagnosis. Conclusions and Relevance: These findings suggest a need for clinical and societal awareness to prevent suicidal behaviors among spouses of patients with cancer, particularly during the first year following the cancer diagnosis.
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OBJECTIVES: It is not clear how chemotherapy-related cognitive impairment and self-care ability affect the quality of life of women with breast cancer. The purpose of this study was to explore the relationships between chemotherapy-related cognitive impairment, self-care ability, and quality of life in breast cancer patients, and test whether self-care ability plays a mediating role in the association between cognitive impairment and quality of life. METHODS: This study was a cross-sectional study, conducted in China in 2022. Self-reported scales were used to assess cognitive function, self-care ability, and quality of life. Data were analyzed using descriptive statistics, spearman correlation analysis and hierarchical multiple regression analyses, the SPSS Process program was used to explore the mediating effect of self-care ability. RESULTS: A total of 218 participants were investigated, and approximately 79.3% of patients experienced mild chemotherapy-related cognitive impairment, the mean quality of life score was 59.96 ± 14.15, and the mean self-care ability score was 107.4 ± 24.09. Significant correlations among cognitive impairment, self-care ability, and quality of life were observed (P < .05). Additionally, self-care ability played a partial mediating role between cognitive impairment and quality of life (P < .05), accounting for 24.3% and 22.3%, respectively. CONCLUSIONS: Chemotherapy-related cognitive impairment and self-care ability are factors affecting the quality of life of breast cancer survivors. Self-care ability mediates the relationship between cognitive impairment and quality of life. Enhancing patients' self-care ability can improve the quality of life of patients with cognitive impairment. IMPLICATIONS FOR NURSING PRACTICE: In the future, oncology nurses should not only pay attention to the severity of cognitive impairment, but also assess the level of patients' self-care ability, provide relevant medical and healthcare guidance, train self-management behavior and strengthen self-care ability by integrating multidisciplinary forces to improve the quality of life of breast cancer patients effectively.
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BACKGROUND: The association between dietary magnesium (Mg) intake and the risk of atherosclerotic cardiovascular disease (ASCVD) remains uncertain. We aimed to examine the associations of dietary Mg intake with the risk of ASCVD events and mortality in individuals with and without type 2 diabetes. METHODS: A total of 149,929 participants (4603 with type 2 diabetes) from the UK Biobank were included in the analyses. The hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated using Cox proportional hazard models. Furthermore, interactions of dietary Mg intake with type 2 diabetes status were examined on multiplicative and additive scales. RESULTS: During a median follow-up of 12.0 and 12.1 years, 7811 incident ASCVD events and 5000 deaths (including 599 ASCVD deaths) were documented, respectively. There were significantly negative associations between sufficient dietary Mg intake (equal to or greater than the recommended daily intake) and the risk of ASCVD incidence (HR 0.63 [95 % CI 0.49;0.82]), ASCVD mortality (0.45 [0.24;0.87]), and all-cause mortality (0.71 [0.52;0.97]) in participants with type 2 diabetes, whereas no significant association was observed in participants without type 2 diabetes (1.01 [0.94;1.09] for ASCVD incidence; 1.25 [0.93;1.66] for ASCVD mortality; 0.97 [0.88;1.07] for all-cause mortality). Multiplicative and additive interactions of dietary Mg intake with type 2 diabetes status were both observed. CONCLUSION: Sufficient dietary Mg intake was significantly associated with lower risks of ASCVD events and mortality in individuals with type 2 diabetes but not in those without type 2 diabetes. Our findings provide insight into the importance of dietary Mg intake for reducing modifiable cardiovascular burden in individuals with type 2 diabetes, which may inform future personalized dietary guidelines.
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Precise control over the size, species, and breakthrough of the activity-selectivity trade-off are great challenges for sub-nano non-noble metal catalysts. Here, for the first time, a "multiheteroatom induced SMSI + in situ P activation" strategy that enables high stability and effective construction of sub-2 nm metal sites for optimizing selective hydrogenation performance is developed. It is synthesized the smallest metal phosphide clusters (<2 nm) including from unary to ternary non-noble metal systems, accompanied by unprecedented thermal stability. In the proof-of-concept demonstration, further modulation of size and species results in the creation of a sub-2 nm site platform, directionally achieving single atom (Ni1), Ni1+metal cluster (Ni1+Nin), or novel Ni1+metal phosphide cluster synergistic sites (Ni1+Ni2Pn), respectively. Based on thorough structure and mechanism investigation, it is found the Ni1+Ni2Pn site is motivated to achieve electronic structure self-optimizing through synergistic SMSI and site coupling effect. Therefore, it speeds up the substrate adsorption-desorption kinetics in semihydrogenation of alkyne and achieves superior catalytic activity that is 56 times higher than the Ni1 site under mild conditions. Compared to traditional active sites, this may represent the highly effective integration of atom utilization, thermal stability, and favorable site requirements for chemisorption properties and reactivities of substrates.
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Ligand-to-metal charge transfer (LMCT) is conceived as a universal theory to account for voltage hysteresis in oxygen-redox battery electrodes. However, the influence of oxygen anionic species on mediating LMCT and its reflection to voltage hysteresis remain poorly understood. Herein, we demonstrate a close interplay between the chemical states of oxidized oxygen species, the cationic species, and the kinetics of LMCT and forcefully identify their influence on the magnitude of voltage hysteresis. Combining electrochemical/spectroscopic evidence and first-principles calculations, we clarify two distinct kinds of dynamic LMCT processesâthat is, the formation of trapped molecular O2 accompanied by the reduction of Ni4+/Ni3+ to Ni2+ (fast LMCT) during relaxation in Li-rich cation-disordered rock-salt (DRX) Li1.3Ni0.27Ta0.43O2 with extremely large voltage hysteresis, the formation of O-O dimers, and the partial reduction of Mn4+ to Mn3+ (slow LMCT) in DRX-Li1.3Mn0.4Ta0.3O2 with medium hysteresis. We further validate the maintenance of both cationic (Mn4+) and anionic (O-â¢) species during relaxation in Na2Mn3O7, reconciling its nonhysteretic behavior to the absence of LMCT. This study highlights the critical role of intermediate anionic species in mediating LMCT and provides a causal explanation of various voltage hysteresis signatures of oxygen-redox materials.
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It is vital to explore effective ways for prolonging electrode lifespans under harsh electrolysis conditions, such as high current densities, acid environment, and impure water source. Here we report alternating electrolysis approaches that realize promptly and regularly repair/maintenance and concurrent bubble evolution. Electrode lifespans are improved by co-action of Fe group elemental ions and alkali metal cations, especially a unique Co2+-Na+ combo. A commercial Ni foam sustains ampere-level current densities alternatingly during continuous electrolysis for 93.8 h in an acidic solution, whereas such a Ni foam is completely dissolved in ~2 h for conventional electrolysis conditions. The work not only explores an alternating electrolysis-based system, alkali metal cation-based catalytic systems, and alkali metal cation-based electrodeposition techniques, and beyond, but demonstrates the possibility of prolonged electrolysis by repeated deposition-dissolution processes. With enough adjustable experimental variables, the upper improvement limit in the electrode lifespan would be high.
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While maternal exposure to high metal levels during pregnancy is an established risk factor for birth defects, the role of paternal exposure remains largely unknown. We aimed to assess the associations of prenatal paternal and maternal metal exposure and parental coexposure with birth defects in singletons. This study conducted within the Jiangsu Birth Cohort recruited couples in early pregnancy. We measured their urinary concentrations for 25 metals. A total of 1675 parent-offspring trios were included. The prevalence of any birth defects among infants by one year of age was 7.82%. Paternal-specific gravity-corrected urinary concentrations of titanium, vanadium, chromium, manganese, cobalt, nickel, copper, and selenium and maternal vanadium, chromium, nickel, copper, selenium, and antimony were associated with a 21-91% increased risk of birth defects after adjusting for covariates. These effects persisted after mutual adjustment for the spouse's exposure. Notably, when assessing the parental mixture effect by Bayesian kernel machine regression, paternal and maternal chromium exposure ranked the highest in relative importance. Parental coexposure to metal mixture showed a pronounced joint effect on the risk of overall birth defects, as well as for some specific subtypes. Our findings suggested a couple-based prevention strategy for metal exposure to reduce birth defects in offspring.
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Anormalidades Congênitas , Exposição Materna , Metais , Humanos , Feminino , Gravidez , Anormalidades Congênitas/epidemiologia , Estudos Prospectivos , Masculino , Metais/urina , Adulto , Coorte de Nascimento , Exposição Paterna , Efeitos Tardios da Exposição Pré-Natal/epidemiologiaRESUMO
Previously, we identified that AP-1 transcription factor FOSL1 is required to maintain cancer stem cells (CSCs) in HNSCC, and an AP-1 inhibitor, T-5224, can eliminate HNSCC CSCs. However, its potency is relatively low, and furthermore, whether T-5224 eradicates CSCs through targeting FOSL1 and whether FOSL1 serves as an effective target for eliminating CSCs in HNSCC, require further validation. We first found that T-5224 can bind to FOSL1 directly. As a proof-of-principle, several cereblon (CRBN)-recruiting PROTACs were designed and synthesized using T-5224 as a warhead for more effective of targeting FOSL1. The top compound can potently degrade FOSL1 in HNSCC, thereby effectively eliminating CSCs to suppress HNSCC tumorigenesis, with around 30 to 100-fold improved potency over T-5224. In summary, our study further validates FOSL1 as an effective target for eliminating CSCs in HNSCC and suggests that PROTACs may provide a unique molecular tool for the development of novel molecules for targeting FOSL1.
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Enhancing the catalytic oxidation activity of traditional transition-metal oxides to rival that of noble metals has been a prominent focus in the field of catalysis. However, existing synthesis strategies that focus on controlling the electronic states of metal centers have not yet fully succeeded in achieving this goal. Our current research reveals that manipulating the electronic states of oxygen centers can yield unexpected results. By creating electron-rich, aperiodic lattice oxygens through atomic topping of MnOx, we have produced a catalyst with performance that closely resembles supported Pt. Spherical aberration-corrected transmission electron microscopy and X-ray absorption spectra have confirmed that the atomic topping of the MnOx layer on Al2O3 can form an aperiodic arrangement oxide structure. Near-ambient pressure X-ray photoelectron spectroscopy, in situ diffuse reflectance infrared Fourier transform spectroscopy, reaction kinetics test, and theoretical calculations demonstrated that this structure significantly increases the electron density around the oxygen in MnOx, shifting the activation center for CO adsorption from Mn to O, thereby exhibiting catalytic activity and stability close to that of the precious metal Pt. This study presents a fresh perspective on designing efficient oxide catalysts by targeting electron-rich anionic centers, thereby deepening the understanding of how these centers can be altered to enhance catalytic efficiency in oxidation reactions.
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Efficient methane photooxidation to formic acid (HCOOH) has emerged as a sustainable approach to simultaneously generate value-added chemicals and harness renewable energy. However, the persistent challenge lies in achieving a high yield and selectivity for HCOOH formation, primarily due to the complexities associated with modulating intermediate conversion and desorption after methane activation. In this study, we employ first-principles calculations as a comprehensive guiding tool and discover that by precisely controlling the O2 activation process on noble metal cocatalysts and the adsorption strength of carbon-containing intermediates on metal oxide supports, one can finely tune the selectivity of methane photooxidation products. Specifically, a bifunctional catalyst comprising Pd nanoparticles and monoclinic WO3 (Pd/WO3) would possess optimal O2 activation kinetics and an intermediate oxidation/desorption barrier, thereby promoting HCOOH formation. As evidenced by experiments, the Pd/WO3 catalyst achieves an exceptional HCOOH yield of 4.67 mmol gcat-1 h-1 with a high selectivity of 62% under full-spectrum light irradiation at room temperature using molecular O2. Notably, these results significantly outperform the state-of-the-art photocatalytic systems operated under identical condition.
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The electron-rich characteristic and low work function endow electrides with excellent performance in (opto)electronics and catalytic applications; these two features are closely related to the structural topology, constituents, and valence electron concentration of electrides. However, the synthesized electrides, especially two-dimensional (2D) electrides, are limited to specific structural prototypes and anionic p-block elements. Here we synthesize and identify a distinct 2D electride of BaCu with delocalized anionic electrons confined to the interlayer spaces of the BaCu framework. The bonding between Cu and Ba atoms exhibits ionic characteristics, and the adjacent Cu anions form a planar honeycomb structure with metallic Cu-Cu bonding. The negatively charged Cu ions are revealed by the theoretical calculations and experimental X-ray absorption near-edge structure. Physical property measurements reveal that BaCu electride has a high electronic conductivity (ρ = 3.20 µΩ cm) and a low work function (2.5 eV), attributed to the metallic Cu-Cu bonding and delocalized anionic electrons. In contrast to typical ionic 2D electrides with p-block anions, density functional theory calculations find that the orbital hybridization between the delocalized anionic electrons and BaCu framework leads to unique isotropic physical properties, such as mechanical properties, and work function. The freestanding BaCu monolayer with half-metal conductivity exhibits low exfoliation energy (0.84 J/m2) and high mechanical/thermal stability, suggesting the potential to achieve low-dimensional BaCu from the bulk. Our results expand the space for the structure and attributes of 2D electrides, facilitating the discovery and potential application of novel 2D electrides with transition metal anions.
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In this study, a Rh(III)-catalyzed C-H/N-H [4+2] annulation of oxadiazolones with iodonium ylides has been developed, which afforded a series of diverse fused-isoquinolines and fused-pyridines in moderate to high yields. These divergent synthesis protocols featured mild conditions, broad substrate scope, and functional-group compatibility. In addition, scale-up synthesis, related applications and preliminary mechanistic explorations were also accomplished.
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Atopic dermatitis (AD) is a common inflammation skin disease that involves dysregulated interplay between immune cells and keratinocytes. Interleukin-38 (IL-38), a poorly characterized IL-1 family cytokine, its role and mechanism in the pathogenesis of AD is elusive. Here, we show that IL-38 is mainly secreted by epidermal keratinocytes and highly expressed in the skin and downregulated in AD lesions. We generated IL-38 keratinocyte-specific knockout mice (K14Cre/+-IL-38f/f ) and induced AD models by 2,4-dinitrofluorobenzene (DNFB). Unexpectedly, after treatment with DNFB, K14Cre/+-IL-38f/f mice were less susceptible to cutaneous inflammation of AD. Moreover, keratinocyte-specific deletion of IL-38 suppressed the migration of Langerhans cells (LCs) into lymph nodes which results in disturbed differentiation of CD4+T cells and decreased the infiltration of immune cells into AD lesions. LCs are a type of dendritic cell that reside specifically in the epidermis and regulate immune responses. We developed LC-like cells in vitro from mouse bone marrow (BM) and treated with recombined IL-38. The results show that IL-38 depended on IL-36R, activated the phosphorylated expression of IRAK4 and NF-κB P65 and upregulated the expression of CCR7 to promoting the migration of LCs, nevertheless, the upregulation disappeared with the addition of IL-36 receptor antagonist (IL-36RA), IRAK4 or NF-κB P65 inhibitor. Furthermore, after treatment with IRAK4 inhibitors, the experimental AD phenotypes were alleviated and so IRAK4 is considered a promising target for the treatment of inflammatory diseases. Overall, our findings indicated a potential pathway that IL-38 depends on IL-36R, leading to LCs migration to promote AD by upregulating CCR7 via IRAK4/NF-κB and implied the prevention and treatment of AD, supporting potential clinical utilization of IRAK4 inhibitors in AD treatment.
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Movimento Celular , Dermatite Atópica , Células de Langerhans , Animais , Dermatite Atópica/metabolismo , Células de Langerhans/metabolismo , Camundongos , Camundongos Knockout , Interleucina-1/metabolismo , Queratinócitos/metabolismo , Dinitrofluorbenzeno , NF-kappa B/metabolismo , Interleucinas/metabolismoRESUMO
Dietary administration of a copper chelator, cuprizone (CPZ), has long been reported to induce intense and reproducible demyelination of several brain structures such as the corpus callosum. Despite the widespread use of CPZ as an animal model for demyelinating diseases such as multiple sclerosis (MS), the mechanism by which it induces demyelination and then allows robust remyelination is still unclear. An intensive mapping of the cell dynamics of oligodendrocyte (OL) lineage during the de- and remyelination course would be particularly important for a deeper understanding of this model. Here, using a panel of OL lineage cell markers as in situ hybridization (ISH) probes, including Pdgfra, Plp, Mbp, Mog, Enpp6, combined with immunofluorescence staining of CC1, SOX10, we provide a detailed dynamic profile of OL lineage cells during the entire course of the model from 1, 2, 3.5 days, 1, 2, 3, 4,5 weeks of CPZ treatment, as well as after 1, 2, 3, 4 weeks of recovery from CPZ treatment. The result showed an unexpected early death of mature OLs and response of OL progenitor cells (OPCs) in vivo upon CPZ challenge, and a prolonged upregulation of myelin-forming OLs compared to the intact control even 4 weeks after CPZ withdrawal. These data may serve as a basic reference system for future studies of the effects of any intervention on de- and remyelination using the CPZ model, and imply the need to optimize the timing windows for the introduction of pro-remyelination therapies in demyelinating diseases such as MS.
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Linhagem da Célula , Cuprizona , Doenças Desmielinizantes , Oligodendroglia , Cuprizona/toxicidade , Animais , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/patologia , Oligodendroglia/efeitos dos fármacos , Oligodendroglia/patologia , Oligodendroglia/metabolismo , Modelos Animais de Doenças , Hibridização In Situ/métodos , Camundongos Endogâmicos C57BL , Camundongos , Remielinização/efeitos dos fármacos , Remielinização/fisiologia , Masculino , Quelantes/toxicidade , Quelantes/farmacologia , Bainha de Mielina/patologia , Bainha de Mielina/efeitos dos fármacos , Bainha de Mielina/metabolismoRESUMO
Integrating anion-redox capacity with orthodox cation-redox capacity is deemed as a promising solution for high-energy-density battery cathodes surmounting the present technical bottlenecks. However, the evolution of oxidized oxygen species during the electrochemical or chemical process easily jeopardizes the reversibility of oxygen redox and remains poorly understood. Herein, we showcase the gradual conversion of the π-interacting oxygen (localized hole states on O) to the σ-interacting oxygen upon resting at a high voltage for P3-type Na0.6Li0.2Mn0.8O2 with nominally stable ribbon-like superstructure, accompanied by the O-O dimerization and the local structural reorganization. We further pinpoint an abnormal Li+ migration process from the alkali-metal layer to the transition-metal layer for desodiated P3-Na0.6Li0.2Mn0.8O2, thereby leading to a partial reconstruction of the ribbon superstructure. The high-voltage plateau of oxygen-redox cathodes is concluded to be exclusively controlled by the oxygen stabilization mechanism rather than the superstructure ordering. In addition, there exists a kinetic competition between π and σ interaction during the uninterrupted electrochemical process.