Metal–organic frameworks (MOFs) incorporating lanthanide nodes and tetrathiafulvalene (TTF) linkers offer a viable approach for combining redox activity and magnetism in one material. Four rare-earth lanthanide ions (RE = Tb, Dy, Ho, and Er) were found to form isostructural MOFs consisting of metal chains bridged by redox-active tetrathiafulvalene-tetrabenzoate (TTFTB4–) whereby the carboxylate moieties act in both anti-anti and syn-syn coordination modes. These materials display tunable redox-active properties and slow magnetic relaxation phenomenon (Er and Dy). While the as-synthesized crystals contain the neutral diamagnetic TTF moiety, using either a solid-solution electrochemical method or iodine oxidation transforms part of the latter to the paramagnetic TTF•+ radical in a single-crystal-to-single-crystal manner without altering the internal structure of the building chains and the frameworks. This is accompanied by inclusion of I3 – replacing some of the solvents, as well as changes in the central C–C bond length of TTFTB, a strong EPR response at g ∼ 2, and an enhancement of the reflectance at low energies originating from absorption by the radical.
Glioma stem-like cells (GSC) promote tumor generation and progression. However, the mechanism of GSC induction or maintenance is largely unknown. We previously demonstrated that the calcium-responsive transcription factor nuclear factor of activated T cells-1 (NFAT1) is activated in glioblastomas and regulates the invasion of tumor cells. In this study, we further explored the role of NFAT1 in GSC. We found that NFAT1 expression was associated with an aggressive phenotype and predicted poor survival in gliomas. Compared with normal glioma cells, NFAT1 was upregulated in GSC. NFAT1 knockdown reduced GSC viability, invasion, and self-renewal in vitro and inhibited tumorigenesis in vivo, whereas NFAT1 overexpression enhanced the growth and invasion of GSCs. RNA sequencing showed that NFAT1 depletion was associated with reduced neurodevelopment protein 1-like 1 (NDEL1, a potential downstream target of NFAT1) expression, whereas NFAT1 overexpression induced NDEL1 expression. In addition, NFAT1 regulated the promoter activities of NDEL1, whereas rescue of NDEL1 in NFAT1-silenced GSC partially restored tumor growth and invasion. Upregulation of NFAT1-NDEL1 signaling elevated Erk activation, increased protein levels of stemness markers in GSC, and resulted in dedifferentiation of normal neuronal cells and astrocytes. Our results indicate that NFAT1 controls the growth and invasion of GSC partially through regulation of NDEL1. Targeting the NFAT1-NDEL1 axis therefore might be of potential benefit in the treatment of patients with glioma.Significance: NFAT1 controls the growth and invasion of GSCs, partially by regulating NDEL1. Targeting the NFAT1-NDEL1 axis might provide opportunities in treating patients with glioma. Immunofluorescence staining of NFAT1 in LN229, G10, and T98G GSCs. DAPI was used for nuclear staining. Scale bar, 25 mm. Results are presented as the mean AE SEM of triplicate samples from three independent experiments. Ã , P < 0.05; ÃÃ , P < 0.01.
Background: Glioblastoma (GBM) is highly proliferative and resistant to radio-chemotherapy. Loss of tumor suppressor gene TP53 function frequently occurs at protein level in GBMs. This inhibition is often mediated by other components within the p53 signaling axis, including MDM2, whose binding protein (MTBP) plays an important role in the regulation of MDM2 and p53 activity. We investigated the role of MTBP in the biology of TP53-wildtype (TP53wt) GBMs.Methods: MTBP expression was examined in TCGA and REMBRANDT datasets. MTBP was silenced or overexpressed in TP53wt GBM cells and glioma stem cells (GSCs). The effects on cell viability, apoptosis, and clonogenicity were assessed. The transcriptional regulation of MTBP was investigated.Results: Upregulation of MTBP was correlated with the Classical molecular subtype, and it predicted poor survival. In TP53wt GBM cells, the protein levels of MTBP were positively associated with those of MDM2 but negatively correlated with those of p53. MTBP knockdown promoted apoptosis and inhibited clonogenicity, while overexpression of this protein enhanced tumorigenicity in vitro and in vivo. The pro-survival effect of MTBP depended on the activity of MDM2 and p53. MTBP was transcriptionally regulated by c-myc, thereby forming a positive regulatory loop. Finally, MTBP silencing increased the sensitivity of TP53wt GSCs to radiation and TMZ treatment in vitro and in vivo.Conclusion: MTBP regulates the cell survival and treatment sensitivity of TP53wt GBMs through MDM2-dependent post-translational modification of p53. MTBP-targeting treatments are potentially useful in increasing patients' survival.
Rationale: Tumor-to-tumor metastasis is a rare clinical phenomenon. Although meningioma is the most common intracranial recipient of cancer metastasis, only a few cases have been reported. We present a case of metastasis of lung adenocarcinoma into intracranial meningioma and review the published literature. Patient concerns: A 70-year-old woman was admitted to our hospital for a 1-month history of headache and pain in her lower extremities. Diagnosis: Brain and lumbar vertebral magnetic resonance imaging showed an intracranial space-occupying lesion in the right occipital region and spinal canal stenosis. Pulmonary computed tomography showed an irregular mass in the right upper lobe of the lung. The postoperative histological examination demonstrated adenocarcinoma metastasis to meningioma. Intervention: The patient underwent right occipital craniotomy for tumor removal and lumbar spinal canal decompression. Outcomes: There were no initial abnormal conditions after the operation. However, the patient died suddenly 7 days after surgery. Lessons: Tumor-to-meningioma metastasis is a rare but important phenomenon. According to previous reports, it is associated with rapid onset of symptoms and a poor prognosis. Histological examination is of great importance in diagnosis. The history and process of malignant carcinoma should be closely monitored.
PurposeMultifocal and multicentric glioblastomas (mGBMs) are associated with a poorer prognosis compared to unifocal glioblastoma (uGBM). The presence of CD8+ tumor-infiltrating lymphocytes (TILs) is predictive of clinical outcomes in human malignancies. Here, we examined the CD8+ lymphocytic infiltration in mGBMs.MethodsThe clinical data of 57 consecutive IDH wildtype primary mGBM patients with histopathological diagnoses were retrospectively reviewed. CD8+ TILs were quantitatively evaluated by immunohistochemical staining. The survival function of CD8+ TILs was assessed by Kaplan–Meier analysis and Cox proportional hazard models.ResultsNo significant difference in the concentration of CD8+ TILs was observed among foci from the same patient (P>0.150). The presence of CD8+ TILs was similar between multifocal and multicentric GBMs (P=0.885). The concentration of CD8+ TILs was significantly lower in mGBMs than in uGBMs (P=0.002). In mGBM patients, the CD8+ TIL level was associated with preoperative KPS (P=0.018). The median overall survival (OS) of the 57 mGBMs was 9 months. A low CD8+ TIL level (multivariate HR 4.404, 95% CI 1.954-9.926, P=0.0004) was an independent predictor of poor OS, while postoperative temozolomide chemotherapy (multivariate HR 6.076, 95% CI 2.330-15.842, P=0.0002) was independently associated with prolonged OS in mGBMs.ConclusionsDecreased CD8+ TIL levels potentially correlate with unfavorable clinical outcome in mGBMs, suggesting an influence of the local immuno-microenvironment on the progression of mGBMs.
The relationship between sleep posture and sleep quality has been studied comprehensively. Over 70% of chronic diseases are highly correlated with sleep problems. However, sleep posture monitoring requires professional devices and trained nursing staff in a medical center. This paper proposes a contactless sleep-monitoring Internet of Things (IoT) system that is equipped with a Raspberry Pi 4 Model B; radio-frequency identification (RFID) tags are embedded in bed sheets as part of a low-cost and low-power microsystem. Random forest classification (RFC) is used to recognize sleep postures, which are then uploaded to the server database via Wi-Fi and displayed on a terminal. The experimental results obtained using RFC were compared to those obtained via the support vector machine (SVM) method and the multilayer perceptron (MLP) algorithm to validate the performance of the proposed system. The developed system can be also applied for sleep self-management at home and wireless sleep monitoring in medical wards.
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