Diagnostic value of Kaiser score combined with breast vascular assessment from breast MRI for the characterization of breast lesions.

Objectives: The Kaiser scoring system for breast magnetic resonance imaging is a clinical decision-making tool for diagnosing breast lesions. However, the Kaiser score (KS) did not include the evaluation of breast vascularity. Therefore, this study aimed to use KS combined with breast vascular assessment, defined as KS*, and investigate the effectiveness of KS* in differentiating benign from malignant breast lesions. Methods: This retrospective study included 223 patients with suspicious breast lesions and pathologically verified results. The histopathological diagnostic criteria were according to the fifth edition of the WHO classification of breast tumors. The KS* was obtained after a joint evaluation combining the original KS and breast vasculature assessment. The receiver operating characteristic (ROC) curve was used for comparing differences in the diagnostic performance between KS* and KS, and the area under the receiver operating characteristic (AUC) was compared. Results: There were 119 (53.4%) benign and 104 (46.6%) malignant lesions in total. The overall sensitivity, specificity, and accuracy of increased ipsilateral breast vascularity were 69.2%, 76.5%, and 73.1%, respectively. The overall sensitivity, specificity, and accuracy of AVS were 82.7%, 76.5%, and 79.4%, respectively. For all lesions included the AUC of KS* was greater than that of KS (0.877 vs. 0.858, P = 0.016). The largest difference in AUC was observed in the non-mass subgroup (0.793 vs. 0.725, P = 0.029). Conclusion: Ipsilaterally increased breast vascularity and a positive AVS sign were significantly associated with malignancy. KS combined with breast vascular assessment can effectively improve the diagnostic ability of KS for breast lesions, especially for non-mass lesions.

Applying Automation and High-Throughput MALDI Mass Spectrometry for Peptide Metabolic Stability Screening.

The discovery of peptide therapeutics represents a fast-growing segment of pharmaceutical research. During the early discovery process, a large number of peptide candidates needs to be rapidly screened for metabolic stability in relevant biological matrices. In most cases, peptide stability assays are quantified using LC-MS/MS, which may take hours to analyze 384 samples and generates liters of solvent waste. Herein, we introduce a high-throughput screening (HTS) platform for peptide stability assessment founded on Matrix Assisted Laser Desorption/Ionization (MALDI) mass spectrometry (MS). Full automation has been implemented for sample preparation with minimal manual intervention. The limit of detection, linearity, and reproducibility of the platform were evaluated, and metabolic stabilities have been determined for a number of peptide candidates. The MALDI-MS-based HTS workflow is able to analyze 384 samples in less than 1 h while only using 115 µL of total solvent. Although this process allows for very rapid assessment of peptide stability, given the nature of the MALDI process, it is noteworthy that spot-to-spot variations and ionization bias are observed. Therefore, LC-MS/MS may still be needed for confident, quantitative measurements and/or when the ionization efficiency of certain peptides is inadequate using MALDI.

Pretreatment-free, on-site separation and sensitive identification of methamphetamine in biological specimens by SERS-active hydrogel microbeads.

The worldwide abuse of illicit drugs led to severe consequences for human health, and society environment. Therefore, urgently required are effective and efficient on-site detection methods for illicit drugs of interest in various matrices, e.g., police samples, biofluids, and hairs. Although surface-enhanced Raman spectroscopy (SERS) shows power in many analytical fields, the cumbersome pretreatment of various matrices restricts its use in the easy-to-operate and on-site detection of illicit drugs. To address this problem, we adopted pore-size selectivity SERS-active hydrogel microbeads, whose meshes are adjustable to allow small molecules to access and to exclude large molecules. Meanwhile, Ag nanoparticles were uniformly dispersed and wrapped in the hydrogel matrix, providing excellent SERS performances with high sensitivity, reproducibility, and stability. By using these SERS hydrogel microbeads, one of the illicit drugs, methamphetamine (MAMP), can be rapidly and reliably detected in various biological specimens (blood, saliva, and hair) without sample pretreatment. The minimum detectable concentration is 0.1 ppm for MAMP in three biological specimens with a linear range of 0.1-100 ppm, which is lower than the maximum allowable level of 0.5 ppm set by the department of the health and human service. The SERS detection results were consistent with the gas chromatographic (GC) data. Thanks to its operational simplicity, fast response, high throughput and low cost, our established SERS hydrogel microbeads can be used as a sensing platform for facile analysis of illicit drugs through simultaneous separation, preconcentration, and optical detection, which shall be provided practically for front-line narcotics squad and resistance to the overwhelmed drug abuses.

One-Step Regio- and Stereoselective Electrochemical Synthesis of Orexin Receptor Antagonist Oxidative Metabolites.

Synthesis of drug metabolites, which often have complex structures, is an integral step in the evaluation of drug candidate metabolism, pharmacokinetic (PK) properties, and safety profiles. Frequently, such synthetic endeavors entail arduous, multiple-step de novo synthetic routes. Herein, we present the one-step Shono-type electrochemical synthesis of milligrams of chiral α-hydroxyl amide metabolites of two orexin receptor antagonists, MK-8133 and MK-6096, as revealed by a small-scale (pico- to nano-mole level) reaction screening using a lab-built online electrochemistry (EC)/mass spectrometry (MS) (EC/MS) platform. The electrochemical oxidation of MK-8133 and MK-6096 was conducted in aqueous media and found to produce the corresponding α-piperidinols with exclusive regio- and stereoselectivity, as confirmed by high-resolution nuclear magnetic resonance (NMR) characterization of products. Based on density functional theory (DFT) calculations, the exceptional regio- and stereoselectivity for this electrochemical oxidation are governed by more favorable energetics of the transition state, leading to the preferred secondary carbon radical α to the amide group and subsequent steric hindrance associated with the U-shaped conformation of the cation derived from the secondary α-carbon radical, respectively.

Functional cotton fabric-based TLC-SERS matrix for rapid and sensitive detection of mixed dyes.

A facile cotton fabric with a built-in TLC-SERS structure was fabricated to demonstrate an integrated TLC separation and SERS identification of mixed dyes. The soft and flexible SERS fabric was firstly fabricated using a simple method in which gold nanoparticles were in-situ synthesized on cotton fabrics by heating. ß-CD was then grafted onto cotton fabric through crosslinking with citric acid in presence of sodium hypophosphite monohydrate via esterification reaction. The adsorption and TLC development performance of ß-CD grafted fabrics were comprehensively investigated with two organic dyes, one anionic dye and one nonionic dye. Besides, the recyclable adsorption and separation performance were tested to evaluate its sustainable application prospects. It displayed less adsorption capacity loss and reusable separation performance after several cycles than the pristine cotton fabrics. Finally, two sets of mixed dyes were successfully separated on the TLC fabrics and then identified via on-site SERS according to their different migration distance. The developed TLC-SERS fabric shows the advantage of quick, easy to handle, low-cost, sensitive, and could be exploited in on-site study of synthetic dyes in art objects, textile and packaging products or forensic applications.

The Optical and Electrical Performance of CuO Synthesized by Anodic Oxidation Based on Copper Foam.

Metal oxide semiconductor materials have a wide range of applications in the field of solar energy conversion. In this paper, CuO was prepared directly on copper foam substrate by anodic oxidation. The effects of current density and anodizing temperature on sample preparation and performance were studied. Field emission scanning electron microscopy (FESEM) and X-ray diffractometer (XRD) had been used to determine the morphology and phase structure of the sample, and its optical and electrical properties were discussed through UV-vis spectrophotometer and electrochemical tests. In addition, the influences of experimental conditions such as current density and reaction temperature on the morphology and properties of CuO were systematically discussed. The FESEM images showed that as the anodic oxidation temperature increase, the morphology of the prepared sample changed from nanowires to leaf-like CuO nanosheets. According to the results of XRD, the structure of prepared CuO was monoclinic, and the intensity of diffraction peaks gradually increased as anodizing temperature increased. We found that the optimum current density and anodizing temperature were 20 mA cm-2 and 60 °C, respectively. The results of electrochemical indicated that the CuO electrode based on copper foam (CuO/Cu foam) prepared at the optimum exhibited the highest specific capacitance (0.1039 F cm-2) when the scan rate was 2 mV s-1.

Definitive Metabolite Identification Coupled with Automated Ligand Identification System (ALIS) Technology: A Novel Approach to Uncover Structure-Activity Relationships and Guide Drug Design in a Factor IXa Inhibitor Program.

A potent and selective Factor IXa (FIXa) inhibitor was subjected to a series of liver microsomal incubations, which generated a number of metabolites. Using automated ligand identification system-affinity selection (ALIS-AS) methodology, metabolites in the incubation mixture were prioritized by their binding affinities to the FIXa protein. Microgram quantities of the metabolites of interest were then isolated through microisolation analytical capabilities, and structurally characterized using MicroCryoProbe heteronuclear 2D NMR techniques. The isolated metabolites recovered from the NMR experiments were then submitted directly to an in vitro FIXa enzymatic assay. The order of the metabolites' binding affinity to the Factor IXa protein from the ALIS assay was completely consistent with the enzymatic assay results. This work showcases an innovative and efficient approach to uncover structure-activity relationships (SARs) and guide drug design via microisolation-structural characterization and ALIS capabilities.

[Characteristics and antioxidant activity of bovine serum albumin and quercetin interaction in different solvent systems].

Modes and influencing factors of bovine serum albumin (BSA) and quercetin (QUE) interaction will help us understand the interaction mechanisms and functional changes of bioactive small molecules and biomacromolecules. The fluorescence spectroscopy, UV-Vis spectroscopy, synchronous fluorescence spectroscopy, DPPH and ABTS radical scavenging assays were used to investigate the characteristics and antioxidant activity of BSA and QUE interaction in three solvent systems (deionized water, dH2O; dimethyl sulfoxide, DMSO and ethanol, EtOH). The results revealed that QUE had a great ability to quench BSA's fluorescence in both static and dynamic modes, and that hydrophobic interaction played a dominant role in BSA and QUE interaction in three solvent systems. The binding constant values and binding site numbers between BSA and QUE were in the order of dH2O>DMSO>EtOH. The binding distances were in the order of EtOH>DMSO>dH2O. On the basis of the binding distance, the binding forces were in the order of dH2O>DMSO>EtOH. The synchronous fluorescence spectra demonstrated that QUE interacted with both tyrosine and tryptophan residues of BSA in three solvent systems. Moreover, the DPPH radical scavenging rates of both QUE and BSA-QUE were 30%. While, the ABTS radical scavenging rate of QUE was significantly decreased from 80% to 70% when bound to BSA. No significant difference in antioxidant activity between QUE and BSA-QUE was observed in three solvent systems.

Ionization mechanism of negative ion-direct analysis in real time: a comparative study with negative ion-atmospheric pressure photoionization.

The ionization mechanism of negative ion-direct analysis in real time (NI-DART) has been investigated using over 42 compounds, including fullerenes, perfluorocarbons (PFC), organic explosives, phenols, pentafluorobenzyl (PFB) derivatized phenols, anilines, and carboxylic acids, which were previously studied by negative ion-atmospheric pressure photoionization (NI-APPI). NI-DART generated ionization products similar to NI-APPI, which led to four ionization mechanisms, including electron capture (EC), dissociative EC, proton transfer, and anion attachment. These four ionization mechanisms make both NI-DART and NI-APPI capable of ionizing a wider range of compounds than negative ion-atmospheric pressure chemical ionization (APCI) or negative ion-electrospray ionization (ESI). As the operation of NI-DART is much easier than that of NI-APPI and the gas-phase ion chemistry of NI-DART is more easily manipulated than that of NI-APPI, NI-DART can be therefore used to study in detail the ionization mechanism of LC/NI-APPI-MS, which would be a powerful methodology for the quantification of low-polarity compounds. Herein, one such application has been further demonstrated in the detection and identification of background ions from LC solvents and APPI dopants, including water, acetonitrile, chloroform, methylene chloride, methanol, 2-propanol, hexanes, heptane, cyclohexane, acetone, tetrahydrofuran (THF), 1,4-dioxane, toluene, and anisole. Possible reaction pathways leading to the formation of these background ions were further inferred. One of the conclusions from these experiments is that THF and 1,4-dioxane are inappropriate to be used as solvents and/or dopants for LC/NI-APPI-MS due to their high reactivity with source basic ions, leading to many reactant ions in the background.

Negative ion-atmospheric pressure photoionization: electron capture, dissociative electron capture, proton transfer, and anion attachment.

To better guide the development of liquid chromatography/electron capture-atmospheric pressure photoionization-mass spectrometry (LC/EC-APPI-MS) in analysis of low polarity compounds, the ionization mechanism of 19 compounds was studied using dopant assisted negative ion-APPI. Four ionization mechanisms, i.e., EC, dissociative EC, proton transfer, and anion attachment, were identified as being responsible for the ionization of the studied compounds. The mechanisms were found to sometimes compete with each other, resulting in multiple ionization products from the same molecule. However, dissociative EC and proton transfer could also combine to generate the same [M - H](-) ions. Experimental evidence suggests that O(2)(-*), which was directly observed in the APPI source, plays a key role in the formation of [M - H](-) ions by way of proton transfer. Introduction of anions more basic than O(2)(-*), i.e., C(6)H(5)CH(2)(-), into the APPI source, via addition of di-tert-butyl peroxide in the solvent and/or dopant, i.e., toluene, enhanced the deprotonation ability of negative ion-APPI. Although the use of halogenated solvents could hinder efficient EC, dissociative EC, and proton transfer of negative ion-APPI due to their EC ability, the subsequently generated halide anions promoted halide attachment to compounds that otherwise could not be efficiently ionized. With the four available ionization mechanisms, it becomes obvious that negative ion-APPI is capable of ionizing a wider range of compounds than negative ion chemical ionization (NICI), negative ion-atmospheric pressure chemical ionization (negative ion-APCI) or negative ion-electrospray ionization (negative ion-ESI).

Electron capture atmospheric pressure photoionization mass spectrometry: analysis of fullerenes, perfluorinated compounds, and pentafluorobenzyl derivatives.

An electron capture (EC) ionization mechanism has been found to be highly efficient in negative-ion atmospheric pressure photoionization (APPI) for the analysis of compounds with positive electron affinity (EA). Using negative-ion APPI, we first report the sensitive detection of natural electrophores with limited polarity, such as fullerenes and perfluorinated compounds, by mass spectrometry (MS). Using direct infusion on a quadrupole time-of-flight (QTOF) mass spectrometer, the limits of detection (LODs) for C(60) and perfluoromethylcyclohexane were determined to be 0.15 pg (0.2 fmol) and 1 femtoliter (fL) ( approximately 1.5 pg or 4.3 fmol), respectively. As the EA of the analyte increases, the detection sensitivity is enhanced. Making use of the accurate mass measurement capability of the QTOF mass spectrometer, we were able to investigate the elemental composition of the ions in each spectrum and attribute the observed high sensitivity to an EC-initiated ionization process. The proposed EC ionization mechanism is further supported by the observation of a dissociative EC reaction of pentafluorobenzyl (PFB)-derivatized phenols. The analysis of phenols by EC-APPI of their PFB derivatives resulted in very high sensitivity, with the lowest reported LOD of approximately 0.17 pg (0.5 fmol) being for 2,4-dinitrophenol. For future LC/EC-APPI-MS applications, the effect of additives and solvents on sensitivity was also tested and reported.

[Comprehensively analysis the correlation between the height of a person and the length of his/her footprint].

OBJECTIVE: Comprehensively analysis the correlation and the law of variation between the height of a person and the length of his/her footprint. METHODS: Collecting footprint samples of those people of different age and sex from different area all of our country, and adopt the regressive analysis method to study these samples. RESULTS: A sum of useful data and regressive equation were obtained. CONCLUSION: The correlation between the height of a person and the length of his/her footprint is obviously, the approximate height of a person can be reckoned according to thelength of his/her footprints.

[Comprehensively analysis the correlation between the height of a person and the length of his/her handprint].

OBJECTIVE: Comprehensively analysis the correlation and the law of variation between the height of a person and the length of his/her handprint. METHODS: Collecting handprint samples of those people of different age and sex from different area all of our country, and adopt the regressive analysis method to study these samples. RESULTS: A sum of useful data and regressive equation were obtained. CONCLUSION: The correlation between the height of a person and the length of his/her handprint is obviously, the approximate height of a person can be reckoned according to the length of his/her handprints.