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Neutral organic radical molecules have recently attracted considerable attention as promising luminescent and quantum-information materials. However, the presence of a radical often shortens their excited-state lifetime and results in fluorescence quenching due to enhanced intersystem crossing (EISC). Recently, an experimental report introduced an efficient luminescent radical molecule, tris(2,4,6-trichlorophenyl)methyl-carbazole-anthracene (TTM-1Cz-An). In this study, we systematically performed quantum theoretical calculations combined with the path integral approach to quantitatively calculate the excited-state dynamics processes and spectral characteristics. Our theoretical findings suggest that the sing-doublet D1 state, originating from the anthracene excited singlet state, is quickly converted to the doublet (trip-doublet) state via EISC, facilitated by a significant nonequivalence exchange interaction, with ΔJ ST = 0.174 cm-1. The formation of the quartet state (Q1, trip-quartet) was predominantly dependent on the exchange coupling 3/2J TR = 0.086 cm-1 between the triplet spin electrons of anthracene and the TTM-1Cz radical. Direct spin-orbit coupling ISC to the Q1 state was minimal due to the nearly identical spatial wavefunctions of the and Q1 levels. The effective occurrence of reverse intersystem crossing (RISC) from the Q1 to D1 state is a critical step in controlling the luminescence of TTM-1Cz-An. The calculated RISC rate k RISC, including the Herzberg-Teller effect, was 3.64 × 105 s-1 at 298 K, significantly exceeding the phosphorescence and nonradiative rates of the Q1 state, thus enabling the D1 repopulation. Subsequently, a strong electronic coupling of 37.4 meV was observed between the D1 and D2 states, along with a dense manifold of doublet states near the D1 state energy, resulting in a larger reverse internal conversion rate k RIC of 9.26 × 1010 s-1. Distributed to the D2 state, the obtained emission rate of k f = 2.98-3.18 × 107 s-1 was in quite good agreement with the experimental value of 1.28 × 107 s-1, and its temperature effect was not remarkable. Our study not only provides strong support for the experimental findings but also offers valuable insights for the molecular design of high-efficiency radical emitters.
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BACKGROUND: Tremor-dominant (TD) and postural instability/gait difficulty (PIGD) are common subtypes of Parkinson's disease, each with distinct clinical manifestations and prognoses. The neural mechanisms underlying these subtypes remain unclear. This study aimed to investigate the altered connectivity of the frontal cortex and supplementary motor area (SMA) in different types of Parkinson's disease. METHODS: Data of 173 participants, including 41 TD patients, 65 PIGD patients, and 67 healthy controls, were retrospectively analyzed. All subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI) and clinical assessments. Differences in amplitude of low frequency fluctuation (ALFF), voxel-wise functional connectivity (FC), and functional network connectivity (FNC) among the three groups were compared, followed by partial correlation analysis. RESULTS: Compared to healthy controls, the left dorsolateral superior frontal gyrus (DLSFG) ALFF was significantly increased in both PIGD and TD patients. The FC between the left DLSFG and the left SMA, as well as between the left paracentral lobule and the right DLSFG, was significantly decreased. Similarly, the FNC between the visual network and the auditory network was reduced. Compared to TD patients, PIGD patients showed a significantly higher ALFF in the left DLSFG and a notably reduced FC between the left DLSFG and left SMA. Additionally, the FC of the left DLSFG-SMA was inversely correlated with the PIGD score exclusively in PIGD patients. The FNC of the visual-auditory network was inversely associated with the tremor score only in TD patients. CONCLUSION: Decreases in the left DLSFG-SMA connectivity may be a key feature of the PIGD subtype, while reduced VN-AUD connectivity may characterize the TD subtype.
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Background: Observational studies have shown that oxidative stress (OS) is associated with Parkinson's disease (PD). However, whether such observations reflect cause-effect remains largely unknown. To test this, we performed a two-sample bidirectional Mendelian randomization (MR) analysis to investigate the causal-effects between OS biomarkers and PD. Methods: We selected summary statistics data for single-nucleotide polymorphisms (SNPs) associated with catalase (n = 13), glutathione peroxidases (n = 12), superoxide dismutase (n = 13), vitamin A (n = 7), vitamin C (n = 10), vitamin E (n = 12), vitamin B12 (n = 8), folate (n = 14), copper (n = 6), Zinc (n = 7), and iron (n = 23) levels, and the corresponding data for PD from the International Parkinson Disease Genomics Consortium (IPDGC, 33,674 cases and 449,056 controls). Inverse-variance weighted (IVW) MR analyses were conducted to estimate associations of OS with PD. Reverse MR analysis was further performed to predict the causal effects of PD on the above OS biomarkers. Results: As for PD, the IVW method suggested that the Zinc (Zn) levels was significantly associated with PD (OR = 1.107, 95% CI 1.013-1.211; p = 0.025), which is consistent with results from the weighted median analyses. Moreover, the results remained consistent and robust in the sensitivity analysis. However, there were no significant associations of catalase, glutathione peroxidases, superoxide dismutase, vitamin A, vitamin C, vitamin E, vitamin B12, folate, copper, or iron with PD. As for OS, our reverse MR analysis also did not support a causal effect of liability to PD on OS. Conclusion: The MR study supported the causal effect of Zn on PD. These findings may inform prevention strategies and interventions directed toward OS and PD.
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Background: Repetitive transcranial magnetic stimulation (rTMS) is an effective noninvasive neuromodulation technique for Parkinson's disease (PD). However, the efficacy of rTMS varies widely between individuals. This study aimed to investigate the factors related to the response to rTMS in PD patients. Methods: We retrospectively analyzed the response of 70 idiopathic PD patients who underwent rTMS for 14 consecutive days targeting the supplementary motor area (SMA) in either an open-label trail (n = 31) or a randomized, double-blind, placebo-controlled trial (RCT) (n = 39). The motor symptoms of PD patients were assessed by the United Parkinson's Disease Rating Scale Part III (UPDRSIII). Based on previous studies, the UPDRSIII were divided into six symptom clusters: axial dysfunction, resting tremor, rigidity, bradykinesia affecting right and left extremities, and postural tremor. Subsequently, the efficacy of rTMS to different motor symptom clusters and clinical predictors were analyzed in these two trails. Results: After 14 days of treatment, only the total UPDRSIII scores and rigidity scores improved in both the open-label trial and the RCT. The results of multiple linear regression analysis indicated that baseline rigidity scores (ß = 0.37, p = 0.047) and RMT (ß = 0.30, P = 0.02) positively predicted the improvement of UPDRSIII. The baseline rigidity score (ß = 0.55, P < 0.0001) was identified as an independent factor to predict the improvement of rigidity. Conclusion: This study demonstrated significant improvements in total UPDRSIII scores and rigidity after 14-day treatment, with baseline rigidity scores and RMT identified as predictors of treatment response, underscoring the need for individualized therapy.
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Background: Colon adenocarcinoma (COAD) has increasing incidence and is one of the most common malignant tumors. The mitochondria involved in cell energy metabolism, oxygen free radical generation, and cell apoptosis play important roles in tumorigenesis and progression. The relationship between mitochondrial genes and COAD remains largely unknown. Methods: COAD data including 512 samples were set out from the UCSC Xena database. The nuclear mitochondrial-related genes (NMRGs)-related risk prognostic model and prognostic nomogram were constructed, and NMRGs-related gene mutation and the immune environment were analyzed using bioinformatics methods. Then, a liver metastasis model of colorectal cancer was constructed and protein expression was detected using Western blot assay. Results: A prognostic model for COAD was constructed. Comparing the prognostic model dataset and the validation dataset showed considerable correlation in both risk grouping and prognosis. Based on the risk score (RS) model, the samples of the prognostic dataset were divided into high risk group and low risk group. Moreover, pathologic N and T stage and tumor recurrence in the two risk groups were significantly different. The four prognostic factors, including age and pathologic T stage in the nomogram survival model also showed excellent predictive performance. An optimal combination of nine differentially expressed NMRGs was finally obtained, including LARS2, PARS2, ETHE1, LRPPRC, TMEM70, AARS2, ACAD9, VARS2, and ATP8A2. The high-RS group had more inflamed immune features, including T and CD4+ memory cell activation. Besides, mitochondria-associated LRPPRC and LARS2 expression levels were increased in vivo xenograft construction and liver metastases assays. Conclusion: This study established a comprehensive prognostic model for COAD, incorporating nine genes associated with nuclear-mitochondrial functions. This model demonstrates superior predictive performance across four prognostic factors: age, pathological T stage, tumor recurrence, and overall prognosis. It is anticipated to be an effective model for enhancing the prognosis and treatment of COAD.
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Adenocarcinoma , Biomarcadores de Tumor , Neoplasias del Colon , Regulación Neoplásica de la Expresión Génica , Humanos , Pronóstico , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Neoplasias del Colon/mortalidad , Adenocarcinoma/genética , Adenocarcinoma/patología , Adenocarcinoma/secundario , Ratones , Animales , Biomarcadores de Tumor/genética , Nomogramas , Biología Computacional/métodos , Genes Mitocondriales , Modelos Animales de Enfermedad , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/patología , Perfilación de la Expresión Génica , Estadificación de Neoplasias , Masculino , Bases de Datos Genéticas , Mitocondrias/genética , Mitocondrias/metabolismo , Mitocondrias/patología , FemeninoRESUMEN
BACKGROUND: Cerebral specialization and interhemispheric cooperation are two vital features of the human brain. Their dysfunction may be associated with disease progression in patients with Alzheimer's disease (AD), which is featured as progressive cognitive degeneration and asymmetric neuropathology. OBJECTIVE: This study aimed to examine and define two inherent properties of hemispheric function in patients with AD by utilizing resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Sixty-four clinically diagnosed AD patients and 52 age- and sex-matched cognitively normal subjects were recruited and underwent MRI and clinical evaluation. We calculated and compared brain specialization (autonomy index, AI) and interhemispheric cooperation (connectivity between functionally homotopic voxels, CFH). RESULTS: In comparison to healthy controls, patients with AD exhibited enhanced AI in the left middle occipital gyrus. This increase in specialization can be attributed to reduced functional connectivity in the contralateral region, such as the right temporal lobe. The CFH of the bilateral precuneus and prefrontal areas was significantly decreased in AD patients compared to controls. Imaging-cognitive correlation analysis indicated that the CFH of the right prefrontal cortex was marginally positively related to the Montreal Cognitive Assessment score in patients and the Auditory Verbal Learning Test score. Moreover, taking abnormal AI and CFH values as features, support vector machine-based classification achieved good accuracy, sensitivity, specificity, and area under the curve by leave-one-out cross-validation. CONCLUSION: This study suggests that individuals with AD have abnormal cerebral specialization and interhemispheric cooperation. This provides new insights for further elucidation of the pathological mechanisms of AD.
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Enfermedad de Alzheimer , Imagen por Resonancia Magnética , Humanos , Enfermedad de Alzheimer/fisiopatología , Enfermedad de Alzheimer/diagnóstico por imagen , Femenino , Masculino , Anciano , Imagen por Resonancia Magnética/métodos , Encéfalo/fisiopatología , Encéfalo/diagnóstico por imagen , Persona de Mediana Edad , Máquina de Vectores de Soporte , Anciano de 80 o más AñosRESUMEN
Dizziness and postural instability are frequently observed symptoms in patient with Parkinson's disease (PD), potentially linked to vestibular dysfunction. Despite their significant impact on quality of life, these symptoms are often overlooked and undertreated in clinical practice. This review aims to summarize symptoms associated with vestibular dysfunction in patients with PD and discusses vestibular-targeted therapies for managing non-specific dizziness and related symptoms. We conducted searches in PubMed and Web of Science using keywords related to vestibular dysfunction, Parkinson's disease, dizziness, and postural instability, alongside the reference lists of relevant articles. The available evidence suggests the prevalence of vestibular dysfunction-related symptoms in patients with PD and supports the idea that vestibular-targeted therapies may be effective in improving PD symptoms.
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Suffering from the formation of metal-ion dendrites and low storage capacity, MXene materials exhibit unsatisfactory performance in Li and Na storage. In this study, we demonstrate that the MXene V3C2Cl2 structure can induce uniform Li and Na deposition. This is achieved through coherent heterogeneous interface reconstruction and regulated ion tiling by halogen surface termination. The high lattice matching (91% and 99%) between MXenes and Li/Na, along with positive Cl terminal regulation, guides Li/Na ions to nucleate uniformly on the V3C2Cl2 MXene matrix and grow in a planar manner. Cl termination proves effective in regulating Li/Na ions due to its moderate adsorption and diffusion coefficients. Furthermore, upon adsorption onto the Cl-terminated V3C2Cl2 monolayer, Li4 and Na4 clusters undergo dissociation, favoring uniform adsorption over cluster adsorption. V3C2Cl2 MXenes exhibit impressive Li/Na storage capacities of 434.07 mA h g-1 for Li and 217.03 mA h g-1 for Na, surpassing the Li storage capacity of Ti3C2Cl2 by three-fold and the Na storage capacity of V2C by 1.4 times. This study highlights the regulatory role of Cl surface terminals in dendrite formation and Li/Na ion deposition, with potential applications to other metal-ion storage electrodes.
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Traffic sources are a major contributor to fine particulate matter (PM2.5) pollution, with their emissions and diffusion exhibiting complex spatiotemporal patterns. Receptor models have limitations in estimating high-resolution source contributions due to insufficient observation networks of PM2.5 compositions. This study developed a source apportionment method that integrates machine learning and emission-based integrated mobile source indicator (IMSI) to rapidly and accurately estimate PM2.5 traffic source impacts with high spatiotemporal resolution in the Beijing-Tianjin-Hebei region. Firstly, we utilized multisource data and developed various machine learning models to optimize the traffic-related pollutant concentration fields simulated by a chemical transport model. Results demonstrated that the Extreme Gradient Boosting (XGBoost) model exhibited excellent prediction accuracy of nitrogen oxide (NO2), carbon oxide (CO), and elemental carbon (EC), with the cross-validated R values increasing to 0.87-0.92 and error indices decreasing by 50-67%. Furthermore, we estimated and predicted daily mappings of PM2.5 traffic source impacts using the IMSI method based on optimized concentration fields, which improved spatially resolved source contributions to PM2.5. Our findings reveal that PM2.5 traffic source impacts display significant spatial heterogeneity, and these hotspots can be precisely identified during the pollution processes with sharp changes. The evaluation results indicated that there is a good correlation (R of 0.79) between PM2.5 traffic source impacts by IMSI method and traffic source contributions apportioned by a receptor model at Beijing site. Our study provides deeper insights of estimating the spatiotemporal distribution of PM2.5 source-specific impacts especially in regions without PM2.5 compositions, which can provide more complete and timely guidance to implement precise air pollution management strategies.
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Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente/métodos , Contaminación del Aire/análisis , Material Particulado/análisis , Óxido Nítrico , Aprendizaje Automático , CarbonoRESUMEN
In this study, the fruit phenotype and quality of 32 superior Wangmo Castanea mollissima plants (designated GM1 to GM32) were examined to identify the trait characteristics of different cluster groups and germplasms with excellent comprehensive performance. The goal was to provide a theoretical basis and research foundation for collecting high-quality germplasm resources and breeding superior cultivars of Wangmo C. mollissima. Ten fruit phenotypic traits and 13 quality traits were measured and analyzed in these 32 superior Wangmo C. mollissima plants. Cluster analysis and principal component analysis (PCA) were used to perform a comprehensive evaluation. Extremely significant positive correlations (P<0.01) were observed for 15 pairs of fruit phenotypic and quality traits, and significant positive correlations (P<0.05) were observed for 16 pairs of traits. Highly significant negative correlations (P<0.01) were observed for 4 pairs of fruit phenotypic and quality traits, and significant negative correlations (P<0.05) were observed for 15 pairs. The plants were divided into three groups by cluster analysis: the first group had large fruits and good fruit quality, the second group had small fruits and poor fruit quality, and the third group had medium-sized fruits with a high starch content. Four principal components were extracted from the 23 traits by PCA, contributing 76.23% of the variance. The ten plants with the highest comprehensive quality were GM32, GM31, GM29, GM1, GM8, GM17, GM10, GM30, GM3 and GM28. The results of this study provide a reference for the development and utilization of Wangmo C. mollissima germplasm resources.
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Fagaceae , Frutas , Frutas/genética , Gangliósido G(M1) , Fitomejoramiento , Fenotipo , Análisis por ConglomeradosRESUMEN
Fe-N-C single-atom nanozymes readily achieved discriminative detection of glutathione (GSH) over other biothiols with similar structure due to the difference between POD-like and OXD-like activities regarding the kind of reactive oxygen species. This colorimetric sensor demonstrated the heterogeneity of GSH levels in different cells and accurately monitored cellular GSH fluctuation.
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Colorimetría , Glutatión , Especies Reactivas de OxígenoRESUMEN
Designing novel two-dimensional (2D) ferroelectric materials by symmetry breaking and studying their mechanisms play important roles in the discovery of new ferroelectric photocatalysts and nanoelectronics. In this study, we have systematically investigated a series of novel ferroelectric 2D HfSnX3 (X = S, Se and Te) monolayers through first-principles calculations. We found that each HfSnX3 monolayer contains a stable ferroelectric phase (FP) and a paraelectric phase (PP). The large polarization (up to 1.64 µC cm-2) in the FP can significantly bend the oxidation reduction potential of water, making HfSnX3 monolayers become excellent ferroelectric photocatalysts. Specifically, by designing a Janus structure to break the symmetry of the PP, we have excitingly obtained a stable Hf2GeSnSe6 (referred to as HGSS) monolayer with triple polarized states. HGSS not only possesses great visible light absorption properties (about 3 × 105 cm-1) as photocatalysts but also successfully solves the dead layer problem previously reported in practical applications. In addition, by constructing a heterostructure with graphene, HGSS has great application in the design of controllable ultrathin p-n junctions. Overall, our study not only predicts a series of potential ferroelectric photocatalytic materials, but also provides valuable insights for designing tunable polarized materials and nanoelectronics.
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We conducted a theoretical investigation into how the molecular stacking effect impacts the photophysical properties in solid phases. Our findings indicated that in the aggregated state, the out-of-plane distorted vibration and imidazole ring stretching vibration of triimidazo-[1,3,5] triazinethe are significantly suppressed, which decreased the Huang-Rhys factor and the corresponding reorganization energy of the photophysical process, as a result, this restricted intramolecular motions and dissipation pathways of excess energy in the excited state, therefore, aggregation induced enhancement emission (AIEE) was found for the title compound from dichloromethane solution to solid state. Analysis of the emission spectrum through discrete spectral lines revealed that the main peak was affected by the vibrational modes with lower frequencies, while the middle-frequency modes influenced the shoulder peak. Furthermore, the predicted intersystem crossing rate (kiosk) and reverse intersystem crossing rate (krisc) using Marcus theory confirmed that an electron can successfully shift from its S1 state to the T1 state, however, the reverse T1 â S1 process can not come into being due to very small krisc (10-6-10-9 s-1), therefore the phosphorescence can be observed. At last, we explored the influence of charge transfer process of the title compound, our theoretical data declared this process can be ignored due to its low transfer rate.
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A highly selective probe for copper(II) detection based on the dansyl group was theoretically studied by means of (time-dependent) density functional theory. The calculated results indicated that the oscillator strength of the fluorescent process for the probe molecule is considerably large, but the counterpart of its copper(II) complex is nearly zero; therefore, the predicted radiative rate kr of the probe is several orders of magnitude larger than that of its complex; however, the predicted internal conversion rate kic of both the probe and its complex is of the same order of magnitude. In addition, the simulated intersystem crossing rate kisc of the complex is much greater than that of the probe due to the effect of heavy atom from the copper atom in the complex. Based on the above information, the calculated fluorescence quantum yield of the probe is 0.16% and that of the complex becomes 10-6%, which implies that the first excited state of the probe is bright state and that of the complex is dark state. For the complex, the hole-electron pair analysis indicates that the process of S0 â S1 belongs to metal-to-ligand charge transfer; its density-of-state diagram visually illustrates that the highest occupied molecular orbital (HOMO) contains the ingredient of the s orbital from the copper atom, which decreases the frontier orbital energy level and the overlap integral of HOMO and LUMO.
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The fungal disease Glomerella leaf spot (GLS) seriously impacts apple production. As a nonprotein amino acid, γ-aminobutyric acid (GABA) is widely involved in biotic and abiotic stresses. However, it is not clear whether GABA is involved in a plant's response to GLS, nor is its molecular mechanism understood. Here, we found that exogenous GABA could significantly alleviate GLS, reduce lesion lengths, and increase antioxidant capacity. MdGAD1 was identified as a possible key gene for GABA synthesis in apple. Further analysis indicated that MdGAD1 promoted antioxidant capacity to improve apple GLS resistance in transgenic apple calli and leaves. Yeast one-hybrid analysis identified the transcription factor MdWRKY33 upstream of MdGAD1. Electrophoretic mobility shift assay, ß-glucuronidase activity, and luciferase activity further supported that MdWRKY33 bound directly to the promoter of MdGAD1. The content of GABA and the transcription level of MdGAD1 in the MdWRKY33 transgenic calli were higher than that of the wild type. When MdWRKY33 transgenic calli and leaves were inoculated with GLS, MdWKRY33 positively regulated resistance to GLS. These results explained the positive regulatory effects of GABA on apple GLS and provided insight into the metabolic regulatory network of GABA.
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Malus , Malus/microbiología , Phyllachorales/metabolismo , Antioxidantes/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Aminoácidos/metabolismoRESUMEN
We have designed and synthesized a novel fluorescent probe BMH for detection of hypochlorous acid (HClO), which can increase dramatically the fluorescence intensity and had ultrafast response, a low detection limit and a wide pH range of application. In this paper, we further studied its fluorescence quantum yield and photoluminescence mechanism theoretically. The calculated results indicated the first excited states of BMH and BM (it was the oxidized product by HClO) were bright states with large oscillator strengths, however, due to more larger reorganization energy of BMH, the predicted internal conversion rate kIC of BMH was four orders of magnitude larger than that of BM; moreover, owing to the effect of heavy atom from sulfur atom in BMH, the predicted intersystem crossing rate kisc of BMH was five orders of magnitude larger than that of BM; meanwhile there was no significant difference found between both the predicted radiative rates kr, thus the calculated fluorescence quantum yield of BMH was nearly zero and that of BM was more than 90%, the data showed the BMH had no fluorescence but its oxidated produce BM possessed strong fluorescence. In addition, the reaction mechanism of BMH transforming into BM has been investigated too, according to the potential energy profile, we found that the course of BMH converting into BM consisted of three elementary reactions. The research results revealed the solvent effect can decreased the activation energy, which was more favorable for these elementary reactions.
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Reactive astrocytes can be transformed into new neurons. Vascular endothelial growth factor (VEGF) promotes the transformation of reactive astrocytes into neurons in ischemic brain. Therefore, in this study, the molecular mechanism of VEGF's effect on ischemia/hypoxia-induced astrocyte to neuron transformation was investigated in the models of rat middle cerebral artery occlusion (MCAO) and in astrocyte culture with oxygen and glucose deprivation (OGD). We found that VEGF enhanced ischemia-induced Pax6, a neurogenic fate determinant, expression and Erk phosphorylation in reactive astrocytes and reduced infarct volume of rat brain at 3 days after MCAO, which effects could be blocked by administration of U0126, a MAPK/Erk inhibitor. In cultured astrocytes, VEGF also enhanced OGD-induced Erk phosphorylation and Pax6 expression, which was blocked by U0126, but not wortmannin, a PI3K/Akt inhibitor, or SB203580, a MAPK/p38 inhibitor, suggesting VEGF enhanced Pax6 expression via activation of MAPK/Erk pathway. OGD induced the increase of miR365 and VEGF inhibited the increase of OGD-induced miR365 expression. However, miR365 agonists blocked VEGF-enhanced Pax6 expression in hypoxic astrocytes, but did not block VEGF-enhanced Erk phosphorylation. We further found that VEGF promoted OGD-induced astrocyte-converted to neuron. Interestingly, both U0126 and Pax6 RNAi significantly reduced enhancement of VEGF on astrocytes-to-neurons transformation, as indicated Dcx and MAP2 immunopositive signals in reactive astrocytes. Moreover, those transformed neurons become mature and functional. We concluded that VEGF enhanced astrocytic neurogenesis via the MAPK/Erk-miR-365-Pax6 signal axis. The results also indicated that astrocytes play important roles in the reconstruction of neurovascular units in brain after stroke.
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Astrocitos , Factor A de Crecimiento Endotelial Vascular , Ratas , Animales , Astrocitos/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Sistema de Señalización de MAP Quinasas , Transdiferenciación Celular , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal , Infarto de la Arteria Cerebral Media/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Neuronas/metabolismo , Glucosa/metabolismoRESUMEN
Developing π electron conjugated groups as covalent bonded bridges between fullerenes in their oligomers is key to optimizing and maximizing functions of the fullerene-based materials. In this work, a series of novel conjugated chain bonded fullerene C60 oligomers (CBFOs) with a well-defined nano-architecture and "grape bunches" shapes are rationally designed and viably constructed based on fullerene-carbenes by means of DFT calculations. The results show that the presently designed CBFOs present a much better electron-accepting ability together with a much lower reorganization energy than the isolated fullerene C60, and characterized as the potential ideal candidate for electron acceptors. The frontier molecular orbital and electron density analysis can well support the results of diabatic electron affinity (EAa) and vertical electron affinity (EAv) calculations. Moreover, these CBFOs exhibit strong absorption in the visible region but no obvious absorption in the ultraviolet region. In addition, the optical properties of the CBFOs and two dimensional structure are also simulated and explored theoretically. We hope that the present study would be helpful for developing covalent-bonded-fullerene based electron trap molecular materials, building blocks of nano-devices and nano-machinery applications.
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BACKGROUND: Breast cancer is one of the most common cancers in women, affecting more than 2 million women worldwide annually. However, effective treatments for breast cancer are limited. Nobiletin is a flavonoid present in the dried mature pericarp of mandarin orange (Citrus reticulata Blanco), which is used to prepare Citri Renetulatae Pericarpium and can inhibit tumour growth and progression according to modern pharmacological studies. However, whether nobiletin exhibits an antimetastatic role in breast cancer and its potential mechanism need to be further investigated. PURPOSE: This study aims to evaluate the inhibitory effect of nobiletin on breast cancer and to elucidate potential mechanisms against invasion and migration. METHODS: Cell viability was determined by cell counting kit-8 and colony formation assays. Wound healing and Boyden chamber assays detected cancer cell migration and invasion capabilities. Immunoblotting and qPCR were applied to determine the protein and mRNA expression levels of extracellular signal-regulated kinases (ERK) and the c-Jun N-terminal kinase (JNK) signalling pathways. Molecular docking was used to assess the degree of nobiletin binding to phosphatidylinositol 3-kinase (PI3K). Xenografts and liver metastases were constructed in BALB/c nude mice to evaluate the anticancer effect of nobiletin in vivo. H&E staining and immunohistochemistry were used to detect proliferation and the expression of related proteins. RESULTS: Nobiletin induced cell death in a concentration- and time-dependent manner and possessed anti-invasion and anti-migration effects on MCF-7 and T47D cells by suppressing the interleukin-6-induced ERK and JNK signalling pathways. In addition, nobiletin docked with the binding site of PI3K, and the binding score was -8.0 kcal/mol. Furthermore, the inhibition of breast cancer growth and metastasis by nobiletin was demonstrated by constructing xenografts and liver metastases in vivo. CONCLUSION: Nobiletin inhibited liver metastasis of breast cancer by downregulating the ERK-STAT and JNK-c-JUN pathways, and its safety and efficacy were verified, indicating the potential of nobiletin as an anticancer agent.
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Quinasas MAP Reguladas por Señal Extracelular , Neoplasias Hepáticas , Animales , Femenino , Humanos , Ratones , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Interleucina-6/farmacología , Ratones Desnudos , Simulación del Acoplamiento Molecular , Fosfatidilinositol 3-Quinasas/metabolismoRESUMEN
Angiogenic factors play an important role in protecting, repairing, and reconstructing vessels after ischemic stroke. In the brains of transient focal cerebral ischemic mice, we observed a reduction in infarct volume after the administration of Angiopoietin 2 (Angpt2), but whether this process is promoted by Angpt2-induced angiogenesis has not been fully elaborated. Therefore, this study explored the angiogenic activities, in reference to CD34 which is a marker of activated ECs and blood vessels, of cultured ECs in vitro and in ischemic damaged cerebral area in mice following Angpt2 administration. Our results demonstrate that Angpt2 administration (100 ng/mL) is neuroprotective by significantly increasing the CD34 expression in in vitro-cultured ECs, reducing the infarct volume and mitigating neuronal loss, as well as enhancing CD34+ vascular length and area. In conclusion, these results indicate that Angpt2 promotes repair and attenuates ischemic injury, and that the mechanism of this is closely associated with angiogenesis in the brain after stroke.