A green and facile direct ink writing technique for preparation calibration standards in laser ablation inductively coupled plasma mass spectrometry analysis.

BACKGROUND: Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) is a powerful tool for microanalysis of solid materials. Nevertheless, one limitation of the method is the lack of well-characterized homogeneous reference materials (RMs), such as BaF2 crystal and BaCO3 ceramics samples, making direct quantification difficult. This work presents a novel Direct Ink Writing (DIW) method to produce RMs for microanalysis. The Mg, Cr, Fe, Co, Ni, Cu, Y, Mo, Pr, Gd, Dy, Ho, Er, Tm, Yb, and Lu solutions were gravimetrically doped into BaCO3 by mixing with the dispersant and then cured with DIW techniques. (94) RESULTS: BaCO3 powder was combined with a dopant analyte to produce a printable slurry, aided by the use of a dispersant and cellulose. The resulting mixture was then printed using DIW equipment. The retention rates of the doped elements were investigated by internal and external standard method, and the results showed that they were completely dispersed in the solid material. After further optimization, it was found that there was no significant heterogeneity among the printed samples. LA-ICP-MS was used to analyze printed samples, to evaluate micro-scale homogeneity. The mass concentration of the doped element was determined by ICP-MS, verify its move closer to nominal value. Compared with the traditional reference materials preparation methods, the DIW technology greatly increased the sample homogeneity and the accuracy of the desired concentration. (132) SIGNIFICANCE: As far as we know, there are few reports on the application of DIW method to prepare calibration standards. In brief, it is proved that the proposed method of preparing calibration standard by DIW technique to quantify analytes is valid and robust. This procedure provides great potential for LA-ICP-MS in-situ analysis in the field of well-prepared products, such as ceramic and crystal samples.(63).

In situ quantitative yttrium and trace elements imaging analysis of Y-doped BaF2 crystals by LA-ICP-MS.

In this study, a laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) method for in-situ determination of yttrium and trace elements in yttrium-doped barium fluoride (BaF2: Y) crystals was proposed. A facile, micro-damage procedure for quantifying the segregation coefficient of doping elements was investigated, and it was found that the actual yttrium doping concentration increases from the seed end to the tail end in BaF2: Y crystals. In micro-area analysis, this method has higher mass sensitivity which was applied to quantify the impurity content and distribution during the growth of BaF2: Y crystals. Regression coefficient of calibration curve for each element ranged from 0.9918 to 0.9995. Detection limits (DLs) were 0.05, 0.03, 0.01 and 0.01 µg g-1 for Mg, Zn, Sr and Pb, respectively. The accuracy of the proposed method was verified by inductively coupled plasma mass spectrometry/atomic emission spectroscopy (ICP-MS/AES) with wet-chemical pretreatment. The objective of the presented work was to provide a less damaging and more novelty approach for crystal sample analysis.

Multi-element Simultaneous sensitization of solution cathode glow discharge atomic emission spectrometry by using portable semiconductor anode refrigeration.

In this study, a modified solution cathode glow discharge atomic emission spectrometry (SCGD-AES) was used to detect metal elements in electroplating sewage. The SCGD-AES device was equipped with a portable semiconductor anode refrigeration unit, which was built independently. The red-heat effect of tungsten electrode was alleviated by adding the portable refrigeration unit, thus improving thermal stability with the withstand voltage from 1040 V to 1140 V. Compared with the devices without semiconductor refrigeration, the chromium was excited more favorable when the discharge voltage increased, and the limit of detection (LOD) decreased by 8.5 times. Furthermore, the LODs of Zn, Cd, Ni, Cu and Pb decreased by 1.8-3.2 times, respectively, which realized the detection of elements in electroplating sewage and showed high performance in the field of trace elements analysis. Furthermore, the accuracy of the method was verified by stream sediment reference material (GBW07312), and the results were consistent with the certified values. The recoveries of elements added to industrial sewage and seawater range were from 90.5 to 98.7%, demonstrating good accuracy of the proposed method.

Evaluation of solution anode glow discharge as a vapor generator in ICP-OES procedures: Application to highly sensitive determination of Cd and Hg.

Herein, we developed a novel microplasma-assisted vapor generation technique based on solution anode glow discharge (SAGD) as a substitute for the pneumatic nebulization (PN) routinely used in inductively coupled plasma-optical emission spectrometry (ICP-OES). Under the optimal state of the newly proposed SAGD-ICP-OES system, the detection limits (DLs) of Cd and Hg were reduced by some 12- and 90-fold respectively, and an average of 2 times for other elements (Ag, Bi, Pb, Tl and Zn) in comparison with conventional PN. This system not only obtained the good detection limits amenable to the ultra-trace determination of Cd (DL = 0.3 µg L-1) and Hg (DL = 0.2 µg L-1), but also retained the ability of multi-element analysis. Its accuracy was demonstrated by the determination of Cd and Hg using GBW07312 (stream sediments) and GBW10029 (fish) certified reference materials (CRMs) and spiked tap water samples. The results showed good consistency with the certified values and the values obtained using inductively coupled plasma-mass spectrometry.

Novel Signal Enhancement Strategy for Laser-Induced Breakdown Spectroscopy via Miniaturized Atmospheric Pressure Glow Discharge.

Herein, a sensitivity enhancement technique for laser-induced breakdown spectroscopy (LIBS) by atmospheric pressure glow discharge was proposed, while cylindrical confinement was used for further improvement. A comprehensive parameters evaluation of the proposed technique was carried out (at the laser energy of 30 mJ), with the emission intensities of Ti, Ni, Cu, Y, Ba, La, Eu, Yb, and Lu in soil samples enhanced by 17.8, 5.7, 5.2, 10.5, 7.4, 6.1, 8.7, 7.8, and 8.7 times, respectively. The limits of detection (LODs) of Ti, Ni, Cu, Y, Ba, La, Eu, Yb, and Lu were significantly decreased from 246, 356, 133, 158, 10, 175, 102, 105, and 262 mg kg-1 to 43, 67, 31, 20, 2, 35, 21, 18, and 49 mg kg-1, respectively. In addition, the possible signal enhancement mechanism was preliminarily explained by studying the plasma electron temperature and density with and without the proposed sensitization strategy.

Therapeutic Response-Based Reclassification of Multiple Tumor Subtypes Reveals Intrinsic Molecular Concordance of Therapy Across Histologically Disparate Cancers.

Cancers that are histologically defined as the same type of cancer often need a distinct therapy based on underlying heterogeneity; likewise, histologically disparate cancers can require similar treatment approaches due to intrinsic similarities. A comprehensive analysis integrated with drug response data and molecular alterations, particularly to reveal therapeutic concordance mechanisms across histologically disparate tumor subtypes, has not yet been fully exploited. In this study, we integrated pharmacological, genomic, and transcriptomic profiling data provided from the Cancer Genome Project (CGP) in a systematic in silico investigation of the pharmacological subtypes of cancers and the intrinsic concordance of molecular mechanisms leading to similar therapeutic responses across histologically disparate tumor subtypes. We further developed a novel approach to redefine cell-to-cell similarity and drug-to-drug similarity from the therapeutic concordance, providing a new point of view to study cancer heterogeneity. This study demonstrates how pharmacological and omics data can be used to systematically classify cancers in terms of response to various compounds and provides us with a purely therapy-oriented perspective to view tumor classifications independent of histology subtypes. The knowledge of pharmacological subtypes of 367 drugs are available via our website (http://www.hywanglab.cn/dtdb/), providing the resources for precision medicine in the perspective of therapeutic response-based re-classification of tumor.

Direct Ultratrace Detection of Lead in a Single Hair Using Portable Electromagnetic Heating Vaporization-Atmospheric Pressure Glow Discharge-Atomic Emission Spectrometry.

In this paper, the first demonstration of direct ultratrace determination of lead in a single human hair by direct current-atmospheric pressure glow discharge-atomic emission spectrometry (DC-APGD-AES) coupled with electromagnetic heating vaporization (EMV) was described. Only the ultramicro mass of a human hair sample (about 0.15 mg, often a single human hair) was required during the analysis, and fast detection was implemented without tedious pretreatment processes, such as grinding and digestion. A limit of detection (LOD) of 30.8 µg kg-1 (4.8 pg) for Pb was obtained under optimized conditions, which was even equivalent to that of conventional LA-ICP-MS/ETV-ICP-MS/GFAAS. EMV-APGD-AES, meanwhile, can facilitate miniaturization and portability with low power and small size. The accuracy and practicality of the method were verified by the analysis of certified reference materials (CRMs) GBW09101b (human hair) and human hair samples from three volunteers. A simple, efficient, and low-cost method for detecting Pb in human hair has been developed.

Fcirc: A comprehensive pipeline for the exploration of fusion linear and circular RNAs.

BACKGROUND: In cancer cells, fusion genes can produce linear and chimeric fusion-circular RNAs (f-circRNAs), which are functional in gene expression regulation and implicated in malignant transformation, cancer progression, and therapeutic resistance. For specific cancers, proteins encoded by fusion transcripts have been identified as innovative therapeutic targets (e.g., EML4-ALK). Even though RNA sequencing (RNA-Seq) technologies combined with existing bioinformatics approaches have enabled researchers to systematically identify fusion transcripts, specifically detecting f-circRNAs in cells remains challenging owing to their general sparsity and low abundance in cancer cells but also owing to imperfect computational methods. RESULTS: We developed the Python-based workflow "Fcirc" to identify fusion linear and f-circRNAs from RNA-Seq data with high specificity. We applied Fcirc to 3 different types of RNA-Seq data scenarios: (i) actual synthetic spike-in RNA-Seq data, (ii) simulated RNA-Seq data, and (iii) actual cancer cell-derived RNA-Seq data. Fcirc showed significant advantages over existing methods regarding both detection accuracy (i.e., precision, recall, F-measure) and computing performance (i.e., lower runtimes). CONCLUSION: Fcirc is a powerful and comprehensive Python-based pipeline to identify linear and circular RNA transcripts from known fusion events in RNA-Seq datasets with higher accuracy and shorter computing times compared with previously published algorithms. Fcirc empowers the research community to study the biology of fusion RNAs in cancer more effectively.

Long non-coding RNA CCAT2 promotes oncogenesis in triple-negative breast cancer by regulating stemness of cancer cells.

Triple-negative breast cancers (TNBC) are more aggressive due to lacking receptors for hormone therapy and maintaining stemness features in cancer cells. Herein we found long non-coding RNA CCAT2 overexpressed specially in TNBC, and in breast cancer stem cells (BCSC) as well. Enforced overexpression and targeted knockdown demonstrated the oncogenic function of CCAT2 both in vitro and in vivo. CCAT2 promoted the expression of stemness markers including OCT4, Nanog and KLF4, increased mammosphere formation and induced ALDH+ cancer stem cell population in TNBC. A chromosomally adjacent gene OCT4-PG1, as a pseudogene of OCT4, was upregulated by CCAT2, and positively regulated the stemness features of TNBC cells. miR-205 was identified as a target gene of CCAT2 in TNBC. Point-mutation in CCAT2 impaired the sponge inhibition of miR-205. Overexpression of miR-205 rescued the oncogenic phenotypes induced by CCAT2. In addition, Notch2, as a target gene of miR-205, was downregulated by miR-205 and upregulated by CCAT2 in TNBC. Collectively, the current study revealed a novel function of CCAT2 in promoting tumor initiation and progression in TNBC through upregulating OCT4-PG1 expression and activating Notch signaling. These findings not only demonstrated a lncRNA-based therapeutic strategy in treatment of TNBC, but also added a node to the regulatory network of CCAT2 that controls aggressiveness of breast cancer stem cells.

An integrative pharmacogenomics analysis identifies therapeutic targets in KRAS-mutant lung cancer.

BACKGROUND: KRAS mutations are the most frequent oncogenic aberration in lung adenocarcinoma. KRAS mutant isoforms differentially shape tumour biology and influence drug responses. This heterogeneity challenges the development of effective therapies for patients with KRAS-driven non-small cell lung cancer (NSCLC). METHODS: We developed an integrative pharmacogenomics analysis to identify potential drug targets to overcome MEK/ERK inhibitor resistance in lung cancer cell lines with KRAS(G12C) mutation (n = 12). We validated our predictive in silico results with in vitro models using gene knockdown, pharmacological target inhibition and reporter assays. FINDINGS: Our computational analysis identifies casein kinase 2A1 (CSNK2A1) as a mediator of MEK/ERK inhibitor resistance in KRAS(G12C) mutant lung cancer cells. CSNK2A1 knockdown reduces cell proliferation, inhibits Wnt/ß-catenin signalling and increases the anti-proliferative effect of MEK inhibition selectively in KRAS(G12C) mutant lung cancer cells. The specific CK2-inhibitor silmitasertib phenocopies the CSNK2A1 knockdown effect and sensitizes KRAS(G12C) mutant cells to MEK inhibition. INTERPRETATION: Our study supports the importance of accurate patient stratification and rational drug combinations to gain benefit from MEK inhibition in patients with KRAS mutant NSCLC. We develop a genotype-based strategy that identifies CK2 as a promising co-target in KRAS(G12C) mutant NSCLC by using available pharmacogenomics gene expression datasets. This approach is applicable to other oncogene driven cancers. FUND: This work was supported by grants from the National Natural Science Foundation of China, the National Key Research and Development Program of China, the Lung Cancer Research Foundation and a Mildred-Scheel postdoctoral fellowship from the German Cancer Aid Foundation.