Unveiling heterogeneity and prognostic markers in ductal breast cancer through single-cell RNA-seq.

BACKGROUND: Breast cancer (BC) is a heterogeneous disease, with the ductal subtype exhibiting significant cellular diversity that influences prognosis and response to treatment. Single-cell RNA sequencing data from the GEO database were utilized in this study to investigate the underlying mechanisms of cellular heterogeneity and to identify potential prognostic markers and therapeutic targets. METHODS: Bioinformatics analysis was conducted using R packages to analyze the single-cell sequencing data. The presence of highly variable genes and differences in malignant potency within the same BC samples were examined. Differential gene expression and biological function between Type 1 and Type 2 ductal epithelial cells were identified. Lasso regression and Cox proportional hazards regression analyses were employed to identify genes associated with patient prognosis. Experimental validation was performed in vitro and in vivo to confirm the functional relevance of the identified genes. RESULTS: The analysis revealed notable heterogeneity among BC cells, with the presence of highly variable genes and differences in malignant behavior within the same samples. Significant disparities in gene expression and biological function were identified between Type 1 and Type 2 ductal epithelial cells. Through regression analyses, CYP24A1 and TFPI2 were identified as pivotal genes associated with patient prognosis. Kaplan-Meier curves demonstrated their prognostic significance, and experimental validation confirmed their inhibitory effects on malignant behaviors of ductal BC cells. CONCLUSION: This study highlights the cellular heterogeneity in ductal subtype breast cancer and delineates the differential gene expressions and biological functions between Type 1 and Type 2 ductal epithelial cells. The genes CYP24A1 and TFPI2 emerged as promising prognostic markers and therapeutic targets, exhibiting inhibitory effects on BC cell malignancy in vitro and in vivo. These findings offer the potential for improved BC management and the development of targeted treatment strategies.

Conjugated Oligoelectrolyte with DNA Affinity for Enhanced Nuclear Imaging and Precise DNA Quantification.

Precise DNA quantification and nuclear imaging are pivotal for clinical testing, pathological diagnosis, and drug development. The detection and localization of mitochondrial DNA serve as crucial indicators of cellular health. We introduce a novel conjugated oligoelectrolyte (COE) molecule, COE-S3, featuring a planar backbone composed of three benzene rings and terminal side chains. This unique amphiphilic structure endows COE-S3 with exceptional water solubility, a high quantum yield of 0.79, and a significant fluorescence Stokes shift (λex = 366 nm, λem = 476 nm), alongside a specific fluorescence response to DNA. The fluorescence intensity correlates proportionally with DNA concentration. COE-S3 interacts with double-stranded DNA (dsDNA) through an intercalation binding mode, exhibiting a binding constant (K) of 1.32 × 106 M-1. Its amphiphilic nature and strong DNA affinity facilitate its localization within mitochondria in living cells and nuclei in apoptotic cells. Remarkably, within 30 min of COE-S3 staining, cell vitality can be discerned through real-time nuclear fluorescence imaging of apoptotic cells. COE-S3's high DNA selectivity enables quantitative intracellular DNA analysis, providing insights into cell proliferation, differentiation, and growth. Our findings underscore COE-S3, with its strategically designed, shortened planar backbone, as a promising intercalative probe for DNA quantification and nuclear imaging.

[The Erythrocyte Deformability Measuring System Based on Microlfuidic and Machine Vision].

The erythrocyte deformability mainly depends on the composition of the membrane and cytoplasm, which consist of hemoglobin and other constituents. The most of current devices to measure erythrocyte deformability require washing process after the measurement which is labor-intensive and time-consuming. This article introduces an improved measuring system based on microfluidic and machine vision (RSD) which adopts disposable microfluidic channel and conventional laser-diffraction technique to determine erythrocyte deformability. To validate the accuracy and repeatability of RSD, several experiments are conducted to determine deformability of normal erythrocytes measured by RSD and a conventional ektacytometer(LORCA). The measured Elongation Index (EI) by RSD, which is a parameter directly related to erythrocyte deformability, is in excel ent agreement with it measured by LORCA.

[Application of Electromagnetic Scanning Technique to EMC Countermeasure for Medical Electrical Equipment].

With practical cases, this paper is to show the major application and according advantages in EMC countermeasure for medical electrical equipment, for instance, rapid fully-scanning, stability to ensure repeatability, precise location of interference source and efficient countermeasure. It is likely helpful and significant to related test being conducted successfully and effectively.

A transient, microfluidic approach to the investigation of erythrocyte aggregation: the threshold shear-stress for erythrocyte disaggregation.

Detailed analysis of red blood cells (RBCs) aggregation is often required in various clinical studies. Most conventional aggregation indices are dimensionless values and not available for comparison of across studies. Quite recently, we have developed microfluidic aggregometry that enables us to yield a critical shear-stress that are required to aggregate RBCs under the shearing hydrodynamic force. The present study investigated the relationships between the values of the critical shear-stress and conventional aggregation indices by comparing the critical shear-stress measured by the microfluidic aggregometry with the threshold shear-stress measured using a LORCA aggregometer. The results showed that the critical shear-stress did not vary with the hematocrit value while the threshold shear-rate decreased with the hematocrit value. The threshold shear-stress also showed the same hematocrit-independence as the critical shear-stress. These findings assist in rheologically validating the critical shear-stress, as defined in the microfluidic aggregometry, within the present range of hematocrit values.