Prelude to malignancy: A gene expression signature in normal mammary gland from breast cancer patients suggests pre-tumorous alterations and is associated with adverse outcomes.

Despite advances in early detection and treatment strategies, breast cancer recurrence and mortality remain a significant health issue. Recent insights suggest the prognostic potential of microscopically healthy mammary gland, in the vicinity of the breast lesion. Nonetheless, a comprehensive understanding of the gene expression profiles in these tissues and their relationship to patient outcomes remain missing. Furthermore, the increasing trend towards breast-conserving surgery may inadvertently lead to the retention of existing cancer-predisposing mutations within the normal mammary gland. This study assessed the transcriptomic profiles of 242 samples from 83 breast cancer patients with unfavorable outcomes, including paired uninvolved mammary gland samples collected at varying distances from primary lesions. As a reference, control samples from 53 mammoplasty individuals without cancer history were studied. A custom panel of 634 genes linked to breast cancer progression and metastasis was employed for expression profiling, followed by whole-transcriptome verification experiments and statistical analyses to discern molecular signatures and their clinical relevance. A distinct gene expression signature was identified in uninvolved mammary gland samples, featuring key cellular components encoding keratins, CDH1, CDH3, EPCAM cell adhesion proteins, matrix metallopeptidases, oncogenes, tumor suppressors, along with crucial genes (FOXA1, RAB25, NRG1, SPDEF, TRIM29, and GABRP) having dual roles in cancer. Enrichment analyses revealed disruptions in epithelial integrity, cell adhesion, and estrogen signaling. This signature, named KAOS for Keratin-Adhesion-Oncogenes-Suppressors, was significantly associated with reduced tumor size but increased mortality rates. Integrating molecular assessment of non-malignant mammary tissue into disease management could enhance survival prediction and facilitate personalized patient care.

The Luminescence of Laser-Produced Carbon Nanodots: The Effect of Aggregation in PEI Solution.

Carbon nanodots (CNDs) produced in pure water by the ablation of graphite with a nanosecond laser pulse exhibit weak photoluminescence. A small addition of polyethyleneimine (PEI) to the aqueous suspension of CNDs causes a significant increase in emissions. This paper presents experimental and theoretical studies of the emission properties of CND/PEI systems. The obtained CNDs responded to even trace amounts of PEI in solution (~0.014% v/v), resulting in a significant increase in the initial weak blue emission of CNDs and PEI taken separately. Morphology and size measurements showed that particle aggregation occurred in the presence of the polymer. A decrease in the calculated Stokes shift values was observed with increasing PEI content in the solution. This indicates a reduction in the number of non-radiative transitions, which explains the increase in the emission intensity of the CND/PEI systems. These results therefore confirmed that the increase in the emission of CND/PEI systems is caused by particle aggregation. Kinetic studies proved that the process is controlled mainly by diffusion, the initial stage of which has a dominant influence on determining the optical properties of the system.

Technological Features for Controlling Steel Part Quality Parameters by the Method of Electrospark Alloying Using Carburezer Containing Nitrogen-Carbon Components.

A new method of surface modification based on the method of electrospark alloying (ESA) using carburizer containing nitrogen-carbon components for producing coatings is considered. New processes have been proposed that include the step of applying saturating media in the form of paste-like nitrogenous and nitrogenous-carbon components, respectively, onto the surface without waiting for those media to dry, conducting the ESA process with the use of a steel electrode-tool, as well as with a graphite electrode-tool. Before applying the saturating media, an aluminium layer is applied onto the surface with the use of the ESA method at a discharge energy of Wp = 0.13-6.80 J. A saturating medium in the form of a paste was applied to the surfaces of specimens of steel C22 and steel C40. During nitriding, nitrocarburizing and carburization by ESA (CESA) processes, with an increase in the discharge energy (Wp), the thickness, micro hardness and continuity of the "white layer" coatings, as well as the magnitude of the surface roughness, increase due to saturation of the steel surface with nitrogen and/or carbon, high cooling rates, formation of non-equilibrium structures, formation of special phases, etc. In the course of nitriding, nitrocarburizing and CESA processing of steels C22 and C40, preliminary processing with the use of the ESA method by aluminum increases the thickness, microhardness and continuity of the "white layer", while the roughness changes insignificantly. Analysis of the phase composition indicates that the presence of the aluminum sublayer leads to the formation of the aluminum-containing phases, resulting in a significant increase in the hardness and, in addition, in an increase in the thickness and quality of the surface layers. The proposed methods can be used to strengthen the surface layers of the critical parts and their elements for compressor and pumping equipment.

The best conditions for the nucleation of carbon nanoparticles in laser-induced plasma.

Despite the existence of many more efficient methods of producing carbon nanoparticles, ablation of a carbon target by a laser pulse remains important. It enables studying the bare properties of nanoparticles, not contaminated with reagents or reaction products. The present work analyses the mechanisms of nucleation and growth of nanoparticles in carbon vapours generated during ablation of graphite with a nanosecond laser pulse. The role of both the homogeneous and the heterogeneous (ions) nucleation was investigated, defining the areas of their occurrence. It has been shown that the most favourable conditions are high pressure of the order 1 GPa and relatively low temperature of about 15 000 K. Such conditions are obtainable when ablation occurs in a liquid and the fluence of the laser pulse is low, exceeding the ablation threshold about 2.7 times only. The resulting nanoparticles are relatively homogeneous and have a diameter of approximately 2.5-5 nm.

Temporal Evolution of Pressure Generated by a Nanosecond Laser Pulse Used for Assessment of Adhesive Strength of the Tungsten-Zirconium-Borides Coatings.

The article presents theoretical and experimental study of shock waves induced by a nanosecond laser pulse. Generation of surface plasma pressure by ablation of the graphite absorption layer in water medium and shock wave formation were analyzed theoretically and experimentally. The amplitude and temporal variation of the shock wave pressure was determined basing on a proposed hydrodynamic model of nanosecond laser ablation and experimentally verified with use of a polyvinylidene fluoride (PVDF) piezoelectric-film sensor. The determined pressure wave was used for examination of adhesive strength of tungsten-zirconium-boride coatings on steel substrate. The magnetron sputtered (MS) W-Zr-B coatings show good adhesion to the steel substrate. The obtained experimental results prove the correctness of the proposed model as well as the suitability of the procedure for assessment of adhesive strength.

Improved Laser Ablation Method for the Production of Luminescent Carbon Particles in Liquids.

An improved method for the production of luminescent carbon nanoparticles is proposed in this work. The new method overcomes the disadvantages of commonly used approaches. It involves two-stage laser ablation in water and in aqueous solutions, where the first stage is the laser ablation of a graphite target and the second is the shredding of particles produced in the first step. The two-stage method offers the optimization of the laser pulse fluence for the performance of each process. It was found that the two-stage process of laser ablation allows producing photoluminescent carbon structures in pure water. The additional reagent may be added either in the first or second stage. The first stage performed in pure water allows avoiding the contamination of the target. Moreover, it simplifies the identification of the origin of photoluminescence. Two synthesis routes for the preparation of carbon nanoparticles by the proposed method using pure water as well as urea aqueous solution are investigated. It was found that the use of urea as a reagent results in luminescence properties similar to those obtained with other more hazardous amine-based reagents. The influence of the synthesis approach and process parameters on the structural and luminescent properties of nanoparticles is also explored in this work.

Luminescent Carbon Dots Synthesized by the Laser Ablation of Graphite in Polyethylenimine and Ethylenediamine.

Fluorescent carbon dots (CDs) synthesized by pulsed laser ablation in liquid (PLAL) are still interesting materials due to their possible applications. However, unlike CDs produced by the hydrothermal method, CDs produced the synthesis products by the PLAL method were never separated by dialysis, which differentiates the synthesis products and allows the identification of the main source of fluorescence. In this work, the synthesis of fluorescent carbon dots (CDs) was performed by nanosecond laser ablation of a graphite target immersed in polyethyleneimine (PEI) and ethylenediamine (EDA), and the synthesis products were separated by dialysis. The results of optical measurements showed that the main source of luminescence of the obtained nanostructures are fluorescent particles or quasi-molecular fluorophores created in the ablation process. In the case of ablation in PEI, most of the produced molecular fluorophores are associated with carbogenic nanostructures, while in the case of EDA, free fluorescent molecules dominate.

Chromosome 22 array-CGH profiling of breast cancer delimited minimal common regions of genomic imbalances and revealed frequent intra-tumoral genetic heterogeneity.

Breast cancer is a common malignancy and the second most frequent cause of death among women. Our aim was to perform DNA copy number profiling of 22q in breast tumors using a methodology which is superior, as compared to the ones applied previously. We studied 83 biopsies from 63 tumors obtained from 60 female patients. A general conclusion is that multiple distinct patterns of genetic aberrations were observed, which included deletion(s) and/or gain(s), ranging in size from affecting the whole chromosome to only a few hundred kb. Overall, the analysis revealed genomic imbalances of 22q in 22% (14 out of 63) of tumors. The predominant profile (11%) was monosomy 22. The smallest identified candidate region, in the vicinity of telomere of 22q, encompasses approximately 220 kb and was involved in all but one of the tumors with aberrations on chromosome 22. This segment is dense in genes and contains 11 confirmed and one predicted gene. The availability of multiple biopsies from a single tumor provides an excellent opportunity for analysis of possible intra-tumor differences in genetic profiles. In 15 tumors we had access to two or three biopsies derived from the same lesion and these were studied independently. Four out of 15 (26.6%) tumors displayed indications of clonal intra-tumor genotypic differences, which should be viewed as a high number, considering that we studied in detail only a single human chromosome. Our results open up several avenues for continued genetic research of breast cancer.

Microarray-based survey of CpG islands identifies concurrent hyper- and hypomethylation patterns in tissues derived from patients with breast cancer.

Maintenance of CpG island methylation in the genome is crucial for cellular homeostasis and this balance is disrupted in cancer. Our rationale was to compare the methylation of CpG islands in tissues (tumor, healthy breast and blood) from patients with breast cancer. We studied 72 genes in 103 samples using microarray hybridization and bisulfite sequencing. We observed tumor specific hyper- or hypomethylation of five genes; COL9A1, MT1A, MT1J, HOXA5 and FLJ45983. A general drop of methylation in COL9A1 was apparent in tumors, when compared with blood and healthy breast tissue. Furthermore, one tumor displayed a complete loss of methylation of all five genes, suggesting overall impairment of methylation. The downstream, evolutionary conserved island of HOXA5 showed hypomethylation in 18 tumors and complete methylation in others. This CpG island also displayed a semimethylated state in the majority of normal breast samples, when compared to complete methylation in blood. Distinct methylation patterns were further seen in MT1J and MT1A, belonging to the metallothionein gene family. The CpG islands of these genes are spaced by 2 kb, which shows selective methylation of two structurally and functionally related genes. The promoters of FLJ45983 and MT1A were methylated above 25% in 18 primary and metastatic tumors. Concurrently, there was also >10% methylation of healthy breast tissue in 11 and 5 samples, respectively. This suggests that the methylation process for the latter two genes takes place already in normal breast cells. Our results also point to a considerable heterogeneity of epigenetic disturbance in breast cancer. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.