Role of a 3D Nanoskeleton in Hindering Electrical Tree Growth in Nanocomposites: Insights from in Situ Self-Fluorescence Imaging.

Despite the proposal of nanodielectrics in 1994, the impact of nano- and microstructures on composite performance is still not completely understood. A key reason for this knowledge gap is the lack of in situ characterization of micro- and nanoscale structures within materials. In this study, we observed the self-excited fluorescence of a microscale-damaged microchannel inside a composite under the influence of an electric field. Furthermore, we conducted in situ imaging of the internal microstructures and discharge channels in the composite utilizing external laser excitation. The imaging results reveal that the electrical treelike damage in the composites grows with a single channel under the guidance of the nanoskeleton embedded in the matrix, which demonstrates that the three-dimensional (3D) nano-order skeleton hinders the development of electrical trees. Furthermore, we analyzed the nanoskeleton intervention's enhancement mechanism on the insulation properties of the composites. This work aids in the precision imaging-guided structural design of nanodielectrics.

Characterization of bone marrow heterogeneity in NK-AML (M4/M5) based on single-cell RNA sequencing.

Normal karyotype acute myeloid leukemia (NK-AML) is a heterogeneous hematological malignancy that contains a minor population of self-renewing leukemia stem cells (LSCs), which complicate efforts to achieve long-term survival. We performed single-cell RNA sequencing to profile 39,288 cells from 6 bone marrow (BM) aspirates including 5 NK-AML (M4/M5) patients and 1 healthy donor. The single-cell transcriptome atlas and gene expression characteristics of each cell population in NK-AML (M4/M5) and healthy BM were obtained. In addition, we identified a distinct LSC-like cluster with possible biomarkers in NK-AML (M4/M5) and verified 6 genes using qRT‒PCR and bioinformatic analyses. In conclusion, we utilized single-cell technologies to provide an atlas of NK-AML (M4/M5) cell heterogeneity, composition, and biomarkers with implications for precision medicine and targeted therapies.

Nondestructive 3D Imaging of Microscale Damage inside Polymers-Based on the Discovery of Self-Excited Fluorescence Effect Induced by Electrical Field.

The development of high-precision, non-destructive, and three-dimensional (3D) in situ imaging of micro-scale damage inside polymers is extremely challenging. Recent reports suggest that 3D imaging technology based on micro-CT technology causes irreversible damage to materials and is ineffective for many elastomeric materials. In this study, it is discovered that electrical trees inside silicone gel induced by an applied electric field can induce a self-excited fluorescence effect. Based on this, high-precision, non-destructive, and 3D in situ fluorescence imaging of polymer damages is successfully achieved. Compared with the current methods, the fluorescence microscopic imaging method enables slicing of the sample in vivo with high-precision operation, realizing the precise positioning of the damaged area. This pioneering discovery paves the way for high-precision, non-destructive, and 3D in situ imaging of polymer internal damage, which can solve the problem of internal damage imaging in insulating materials and precision instruments.

In Situ Self-Fluorescence 3D Imaging of Micro/Nano Damage in Silicone Gel for Understanding Insulation Failure under High-Frequency Electric Fields.

Strong electromagnetic and heat flux stresses can induce severe damage to solid insulation materials, leading to faults in power equipment and power electronics devices. However, in the absence of suitable in situ imaging methods for observing the development and morphology of electrical damage within insulation materials, the mechanism of insulation failure under high-frequency electric fields has remained elusive. In this work, a recently discovered fluorescence self-excitation phenomenon in electrical damage channels of polymers is used as the basis for a laser confocal imaging method that is able to realize three-dimensional (3D) in situ imaging of electrical tree channels in silicone gel through nondestructive means. Based on the reconstructed morphology of the damaged area, a spatial equivalent calculation model is proposed for analysis of the 3D geometric features of electrical trees. The insulation failure mechanism of silicone gel under electric fields of different frequencies is analyzed through ReaxFF molecular dynamics simulations of the thermal cracking process. This work provides a new method for in situ nondestructive 3D imaging of micro/nanoscale damage structures within polymers with potential applications to material analysis and defect diagnosis.

Expression and clinical significance of RAG1 in myelodysplastic syndromes.

OBJECTIVE: To determine the expression level of RAG1 and its clinical significance in myelodysplastic syndromes (MDS). METHODS: To explore the candidate genes, the microarray datasets GSE19429, GSE58831, and GSE2779 were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) in MDS were screened using RStudio, and overlapped DEGs were obtained with Venn Diagrams. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses, and protein-protein interaction network were performed. Quantitative real-time PCR (qRT-PCR) was employed to confirm the microarray results. RESULTS: This study identified 26 DEGs. Functional enrichment analyses indicated that these DEGs were significantly enriched in the immune response, and hematopoietic cell lineage. Eight core genes, for example, RAG1 and PAX5, were identified with a high degree of connectivity. The result of qRT-PCR showed that RAG1 was significantly down-regulated in MDS patients, which helped in distinguishing MDS patients from normal controls. The area under the curve of the receiver operator characteristic was 0.913 (P < 0.0001). MDS patients with low RAG1 expression level had a poor long-term survival (P = 0.031). What's more, the expression of RAG1 was significantly increased in the patients who received treatment. CONCLUSION: The results showed that the expression of RAG1 was down-regulated in MDS patients. Lower RAG1 expression was associated with adverse clinical outcomes. RAG1 may be a potential prognostic biomarker for MDS.

An immune-related gene prognostic index for acute myeloid leukemia associated with regulatory T cells infiltration.

Acute myeloid leukemia (AML) is a malignant clonal disease characterized by abnormal proliferation of immature myeloid cells and bone marrow failure. Regulatory T cells (Treg) play a suppressive role in the anti-tumor immune response in the tumor microenvironment. Screening biomarkers based on Treg immune-related genes may help to predict the prognosis and the efficacy of immunotherapy of AML.Gene expression profiles of AML (non-M3) were obtained from the TCGA and GEO databases. Gene module related to Treg was extracted using CIBERSORT and WGCNA algorithms. Univariate Cox regression and LASSO analyses were performed to identify hub genes and constructed the immune prognostic model. Molecular and immunological features associated with risk signature were explored, and TIDE was used to predict the efficacy of immunotherapy.A risk signature was constructed based on the five IRGs (IFI27L1, YIPF6, PARVB, TRIM32 and RHOBTB3). The risk signature could be served as an independent prognostic factor of AML. Patients in the high-risk group had a poorer OS than those in the low-risk group. In addition, patients in the high-risk group had higher TP53 mutation rate, higher infiltration of Treg, higher immune escape potential and less benefit from ICI therapy compared to low-risk group.Our study constructed a prognostic index based on five Treg-related biomarkers, which help to facilitate the differentiation of immunological and molecular characteristics of AML, predict patient prognosis and provide a reference for predicting benefits from ICI therapy.

MiR-181a-2-3p as a potential diagnostic and prognostic marker for myelodysplastic syndrome.

OBJECTIVE: Myelodysplastic syndrome (MDS) is a clonal bone marrow disorder with a high propensity to develop into acute myeloid leukemia (AML). Although abnormal microRNA expression has been implicated in MDS, the exact role of miR-181a-2-3p has not been entirely elucidated. Here, we investigated miR-181a-2-3p levels in bone marrow (BM), and described its utility as a potential indicator for MDS diagnosis and prognosis. METHODS: We evaluated miR-181a-2-3p expression in BM samples of 54 newly diagnosed MDS cases, 16 sAML patients and 32 healthy donors and then assessed its association with clinical characteristics and its potential value for MDS diagnosis and prognosis. RESULTS: Compared with healthy controls, miR-181a-2-3p levels were decreased in the total cohort of MDS patients. Additionally, in MDS patients with secondary AML (sAML), miR-181a-2-3p was over-expressed relative to levels in those without this form. The areas under the curve of receiver operating characteristic curves were 0.700 and 0.750 to distinguish MDS patients from controls and sAML from newly diagnosed MDS, respectively. Kaplan-Meier analysis showed a positive correlation between miR-181a-2-3p expression and overall survival (OS). Further, multivariate analysis indicated that miR-181a-2-3p was an independent prognostic index for MDS with respect to OS. CONCLUSION: Decreased miR-181a-2-3p expression in MDS patients may be considered as one of the underlying markers reflecting MDS progression and prognosis.

[Effects of Paclitaxel and Quizartinib Alone and in Combination on AML Cell Line MV4-11 and Its STAT5 Signal Pathway].

OBJECTIVE: To investigate the effects of paclitaxel, quizartinib and their combination on proliferation, apoptosis and FLT3/STAT5 pathway of human leukemia cell line MV4-11 (FLT3-ITD+). METHODS: MV4-11 cells were treated with paclitaxel and quizartinib at different concentrations for 24 h, 48 h and 72 h, respectively, and then the two drugs were combined at 48 h to compare the inhibition of proliferation, the apoptosis rate was detected by flow cytometry, the expression of FLT3 and STAT5 mRNA was determined by fluorescence quantitative PCR, and the protein expression of FLT3, p-FLT3, STAT5 and p-STAT5 was determined by Western blot. RESULTS: Different combination groups of paclitaxel and quizartinib had synergistic inhibitory effect. The cell survival rate in the combination group was significantly lower than that in the single drug group (P<0.05). The cell apoptosis rate in the combination group was significantly higher than that in the single drug group (P<0.001). The expression of FLT3 mRNA in combination group was significantly higher than that in two single drugs (P<0.01). The expression of STAT5 mRNA in combination group was significantly higher than that in quizartinib group (P<0.001); increased compared with paclitaxel group, but there was no statistical significance. The expression level of p-FLT3、p-STAT5 protein in the combination group was significantly lower than that in the single drug group (P<0.05, P<0.05). CONCLUSION: Paclitaxel combined with quizartinib can synergistically inhibit the proliferation of MV4-11 cell line and promote the apoptosis of MV4-11 cell line by inhibiting the activity of FLT3/STAT5 pathway.

[Exploring the Mechanism of Paclitaxel Inhibiting T-cell Lymphoma based on High-throughput Sequencing and Public Databases].

OBJECTIVE: To analyze gene expression profile of T cell lymphoma Jurkat cell line treated with paclitaxel by computational biology based on next generation sequencing and to explore the possible molecular mechanism of paclitaxel resistance to T cell lymphoma at gene level. METHODS: IC50 of paclitaxel on Jurkat cell line was determined by CCK-8 assay. Gene expression profile of Jurkat cells treated with paclitaxel was acquired by next generation sequencing technology. Gene microarray data related to human T cell lymphoma were screened from Gene Expression Omnibus (GEO) database (including 720 cases of T cell lymphoma and 153 cases of normal tissues). Combined with the sequencing data, differential expression genes (DEGs) were intersected and screened. DAVID database was used for enrichment analysis of GO function and KEGG pathway to determine and visualize functional entries of DEGs, and protein-protein interactions network of DEGs was drawn. The levels of gene expression were detected and verified by RT-qPCR. RESULTS: CCK-8 results showed that the proliferation of Jurkat cells was inhibited by paclitaxel depended on the concentration apparently. Treated by paclitaxel for 48 h, P<0.05 and |log2(FC)|≥1 were used as filter criteria on the results of RNA Sequencing (RNA-Seq) and GeoChip, 351 DEGs were found from Jurkat cells, including 323 up-regulated genes and 28 down-regulated genes. The GO functional annotation and KEGG pathway enrichment analysis showed that the role of paclitaxel was mainly concentrated in protein heterodimerization activity, nucleosome assembly and transcriptional dysregulation in cancer, etc. The results of RT-qPCR were consistent with those of the sequencing analysis, which verified the reliability of this sequencing. CONCLUSION: Paclitaxel can affect the proliferation and apoptosis of T-cell lymphoma by up-regulating JUN gene, orphan nuclear receptor NR4A family genes and histone family genes.

An occult urothelial carcinoma with wide multiorgan metastases and its genetic alteration profiling: Case report and literature review.

RATIONALE: Urothelial carcinoma, also named transitional cell carcinoma, is the most frequent occurring malignancy in the urinary system. It mainly invades the surrounding tissues and metastasizes to distant organs in later stages. PATIENT CONCERNS: Here, we presented an unusual case of occult urothelial carcinoma primarily manifested as a multiorgan metastatic cancer in a 59-year-old man. The patient complained of pain on the left thigh root for a month. The imaging and histopathological examination revealed multiple malignancies in lung, bone, and liver. DIAGNOSES: The histological evaluation and the immunohistochemistry (IHC) profile of liver, lung, and bone were consistent with the diagnosis of metastases from the original urothelial cancer, while imaging examination was not able to detect a primary lesion in the urinary system. INTERVENTIONS: Based on the mutation of STK11 M51Ifs*106 detected by next generation sequencing (NGS), we started targeted therapy with everolimus. OUTCOMES: The patient deteriorated after 3 months of treatment and passed away. LESSONS: In this initial report of occult urothelial carcinoma, we obtained information on genetic variations of tumor tissue which could provide important information for subsequent studies on this kind of disease.