Assessment of pheniramine in alternative biological matrices by liquid chromatography tandem mass spectrometry.

Pheniramine is an over-the-counter antihistamine drug. Its accessibility and low cost made it more popular among drug abusers in Pakistan. In this study, pheniramine was quantified in both conventional and alternative specimens of twenty chronic drug abusers, aged 16-50 years, who were positive for pheniramine in comprehensive toxicological screening for drugs by gas chromatography with mass spectral detection in positive electron impact mode. Pheniramine was extracted from biological specimens using solid phase extraction and liquid chromatography tandem mass spectrometry was employed for quantification. Chromatographic separation was carried out on a Poroshell120EC-18 (2.1 mm × 50 mm × 2.7 µm) column using water-acetonitrile in formic acid (0.1%) mobile phase in gradient elution mode with 500 µL/min flow rate. Positive electrospray ionization mode and multi-reaction monitoring with ion transitions m/z 241.3 → 195.8 and 167.1 for pheniramine and m/z m/z 247.6 → 173.1 for pheniramine-d6 were employed. The quantification method showed good linear ranges of 2-1000 ng/mL in blood, urine, and oral fluid; 2-1000 ng/mg in hair and 5-1000 ng/mg in nail with ≥ 0.985% coefficient of linearity. The retention time of pheniramine was 3.0 ± 0.1 min. The detection and lower quantification limits were 1 ng/mL and 2 ng/mL for blood, urine, oral fluid and hair whereas 2.5 ng/mg and 5 ng/mg for nail, respectively. Mean extraction recovery and ionization suppression ranged 86.3-95.1% and -4.6 to -14.4% in the studied matrices. Intra-day and inter-day precision were 4.1-9.3% and 2.8-11.2%, respectively. Pheniramine levels in specimens of drug abusers were 23-480 ng/mL in blood, 72-735 ng/mL in urine, 25-379 ng/mL in oral fluid, 10-170 ng/mg in hair and 8-86 ng/mg in nail specimens. Alternative specimens are of utmost significance in clinical and medico-legal cases. In this study, authors compared matrix-matched calibration curves to blood calibration curve and obtained results within ± 10%; thereby justifying the use of blood calibration curve for urine, oral fluid, hair, and nail specimens.

Single-nucleobase resolution of a surface energy transfer nanoruler for in situ measurement of aptamer binding at the receptor subunit level in living cells.

In situ identification of aptamer-binding targets on living cell membrane surfaces is of considerable interest, but a major challenge, specifically, when advancing recognition to the level of membrane receptor subunits. Here we propose a novel nanometal surface energy transfer (NSET) based nanoruler with a single-nucleobase resolution (SN-nanoruler), in which FAM-labeled aptamers and single-sized gold nanoparticle (GNP) antibody conjugates act as a donor and an acceptor. A single nucleobase resolution of the SN-nanoruler was experimentally illustrated by molecular size, orientation, quenching nature, and other dye-GNP pairs. The SN-nanoruler provides high reproducibility and precision for measuring molecule distance on living cell membranes at the nanometer level owing to only the use of single-sized antibody-capped GNPs. In situ identification of the aptamer binding site was advanced to the protein subunit level on the living cell membrane for the utilization of this SN-nanoruler. The results suggest that the proposed strategy is a solid step towards the wider application of optical-based rulers to observe the molecular structural configuration and dynamic transitions on the membrane surface of living cells.

Machine learning-based guilt detection in text.

We introduce a novel Natural Language Processing (NLP) task called guilt detection, which focuses on detecting guilt in text. We identify guilt as a complex and vital emotion that has not been previously studied in NLP, and we aim to provide a more fine-grained analysis of it. To address the lack of publicly available corpora for guilt detection, we created VIC, a dataset containing 4622 texts from three existing emotion detection datasets that we binarized into guilt and no-guilt classes. We experimented with traditional machine learning methods using bag-of-words and term frequency-inverse document frequency features, achieving a 72% f1 score with the highest-performing model. Our study provides a first step towards understanding guilt in text and opens the door for future research in this area.

The ARF2-MYB6 module mediates auxin-regulated petal expansion in rose.

In cut rose (Rosa hybrida), the flower-opening process is closely associated with vase life. Auxin induces the expression of transcription factor genes that function in petal growth via cell expansion. However, the molecular mechanisms underlying the auxin effect during flower opening are not well understood. Here, we identified the auxin-inducible transcription factor gene RhMYB6, whose expression level is high during the early stages of flower opening. Silencing of RhMYB6 delayed flower opening by controlling petal cell expansion through down-regulation of cell expansion-related genes. Furthermore, we demonstrated that the auxin response factor RhARF2 directly interacts with the promoter of RhMYB6 and represses its transcription. Silencing of RhARF2 resulted in larger petal size and delayed petal movement. We also showed that the expression of genes related to ethylene and petal movement showed substantial differences in RhARF2-silenced petals. Our results indicate that auxin-regulated RhARF2 is a critical player that controls flower opening by governing RhMYB6 expression and mediating the crosstalk between auxin and ethylene signaling.

Synthesis of bimetallic core-shelled nanoparticles modified by 2-mercaptoethanol as SERS substrates for detecting ferbam and thiabendazole in apple puree.

Modification of surface-enhanced Raman spectroscopy (SERS) substrates with thiol ligands is an emerging approach in enhancing the stability and sensitivity of metal substrates due to their good affinity with metals such as Au, Ag, and Cu. Thus, in the current study, 2-mercaptoethanol was used to modify the surface of silver-coated gold nanoparticles to develop a novel SERS substrate for the rapid assessment of fungicide residues in fruit samples. Results showed that the substrate could achieve the detection of ferbam and thiabendazole residues in apple puree with limits of detection of approximately 0.0042 and 0.0064 ppm, high coefficients of determination of 0.9946 and 0.9968, good recoveries ranging from 80 to 105 and 81 to 107% and relative standard deviations of 3.5-7.5 and 3.8-7.9 %, respectively. Therefore, the substrate developed could potentially be utilised to assess other toxic agrochemicals in future.

Core size optimized silver coated gold nanoparticles for rapid screening of tricyclazole and thiram residues in pear extracts using SERS.

Silver-coated gold nanoparticles (Au@AgNPs) were optimized with different gold (Au) core sizes and modified surface with mercaptooctane (MCO) to determine fungicide residues in pear fruit extracts. The developed MCO/Au@AgNPs with a gold core size of 28 nm and silver shell thickness of 6 nm exhibited high sensitivity and significant enhancement of Raman scattering in detecting tricyclazole (TCZ) and thiram fungicides in standard and pear fruit samples. The detection limits for TCZ and thiram in the pear fruit extracts were 0.005 and 0.003 ppm with coefficients of determination of (R2) of 0.9984 and 0.9971, percent recovery ranging from 82.7 to 107.4% and 80.7 to 109.8%, and relative standard deviation (RSD) of 1.5 to 7.9% and 3.7 to 9.5%, respectively. Results showed that this easily prepared method could be employed as SERS active platforms for the rapid assessment of trace contaminants of agrochemicals in agriculture production.

Rapid detection of ziram residues in apple and pear fruits by SERS based on octanethiol functionalized bimetallic core-shell nanoparticles.

Existing approaches for the screening of unsafe materials in food matrices are time-consuming, tiresome and destructive in nature. Therefore, in the current study, a surface-enhanced Raman spectroscopy (SERS) method based on octanethiol-functionalized core-shell nanoparticles (Oct/Au@AgNPs) was established for rapid detection of ziram in apple and pear fruits. The morphology of substrate was evaluated using high-resolution TEM images and superimposed HAADF-STEM-EDS elemental mapping images, which confirmed that Au@AgNPs having gold (Au) core size of 28 nm in diameter and silver (Ag) shell of 5.5 nm in thickness were successfully grafted with octanethiol. The SERS method with the sensitive nanoparticles could detect ziram of up to 0.015 and 0.016 ppm in apple and pear with high coefficients of determination (R2) of 0.9987 and 0.9993, respectively. Furthermore, satisfactory recoveries (80-106%) were also accomplished for the fungicide in real samples. This work demonstrated that the functionalized silver-coated gold nanoparticles were easy to prepare and could be used as sensitive SERS platforms for monitoring of other agrochemicals in foods.

Fabrication of anti-vitiligo ointment containing Psoralea corylifolia: in vitro and in vivo characterization.

BACKGROUND: Vitiligo is a repugnant and odious dermatological malady of the time. It has an detrimental impact on the pigmentation of the human skin as a result of the destruction of cutaneous melanocytes. It affects 1%-2% of the population worldwide. Different therapeutic regimens have been deployed to treat vitiligo, but none of them could stand alone to be stated as a perfect cure. Recently, a change has been observed through novel experimental-designed optimization leading to the development of an anti-vitiligo ointment containing Psoralea corylifolia (PC) seed powder. AIM: The aim of this study was to explore the clinical outcomes of ointment containing powdered seeds of PC. MATERIALS AND METHODS: Guided by the protocol Response Surface Methodology, 13 formulations of concentration variance of permeation enhancers were prepared. The formulation fulfilling the required criteria (pH; temperature stability tests at 8°C±0.1°C, 25°C±0.1°C and 40°C±0.1°C; and the physical properties such as color, bleeding and rheology) was selected for clinical trials. Fourier transform infrared spectroscopy studies of seed powder of PC and selected formulation of the seed powder were performed. After obtaining informed consents and with prior approval of university and hospital ethical review boards, 20 patients (age range 25-65 years) were included in the present study. Formulations were applied on the affected body parts of patients, and some affected portion of the same patient was taken as control (self-control study design). The pigmentation of white spots of vitiligo was photographically evaluated before, during and after 12 weeks of treatment. Analysis of the measured values was performed using GraphPad Prism version 5 statistical software. A paired sample t-test was performed to observe variation between repigmented patches and white patches of self-control. RESULTS: Hydrophilic ointment (10% w/w) prepared with seed powder of PC was fabricated. The ointment was found effective for small circular white lesions of vitiligo as compared to self-control. Pre- and post-treatment differences in the levels of pigmentation were statistically significant (P≤0.05). CONCLUSION: Ointment containing seed powder of PC could be an effective monotherapy for small circular white lesions of vitiligo.

24-Methyl-lanosta-7,25-dien-3-one.

THE TITLE COMPOUND [SYSTEMATIC NAME: 17-(5,6-di-methyl-hept-6-en-2-yl)-4,4,10,13,14-penta-methyl-1,5,6,10,11,12,13,15,16,17-deca-hydro-2H-cyclo-penta-[α]phenanthren-3(4H,9H,14H)-one], C(31)H(50)O, is a triterpenoid which was isolated from Skimmia laureola. The three six-membered rings adopt chair, slightly distorted half-chair and distorted boat conformations, and the five-membered ring is in an envelope conformation. All the rings are trans fused. In the crystal structure, there is a weak C-H⋯O hydrogen bond.

O-Methyl cyclo-laudenol.

THE TITLE COMPOUND (SYSTEMATIC NAME: 3-meth-oxy-24-methyl-9,19-cyclo-lanost-25-ene), C(32)H(54)O, is a triterpenoid which has been isolated from Skimmia laureola. The three six-membered rings adopt chair, slightly distorted half-chair and distorted boat conformations, and the five-membered ring adopts an envelope conformation. All the rings are trans fused.

Patterns of pancytopenia patients in a general medical ward and a proposed diagnostic approach.

BACKGROUND: There has been little systematic study on the clinical spectrum of pancytopenia. This study was done to describe the etiology, presentation and outcome of patients with pancytopenia presenting in a general medical ward. METHODS: Hundred patients with pancytopenia were included in the study from October 2001 to October 2002. Patients on cancer chemotherapy were excluded. Blood counts, bone marrow examinations and trephine biopsies were performed according to standard methods. RESULTS: In all cases, megaloblastic anemia constituted the largest group (n = 39), and also seen in conjunction with hemolytic anemia and septicemia. Hypersplenism secondary to portal hypertension (cirrhosis) was the second most common diagnosis (n = 19). Aplastic anemia, septicemia and myelodysplasia were other common causes. Two patients were the suspected cases of viral hemorrhagic fever. Thirteen (13%) patients expired. Absolute neutrophil count (ANC) less than 500/microliter was seen in 14 (14%) patients, among which 6 (15.3%) had megaloblastic anemia, 3 (37.5%) had aplastic anemia, and 2 (40%) had myelodysplasia. Eleven patients with platelet counts < or = 10 x 10(9)/L, 6 (54.5%) presented with bleeding; and 2 of these 8 had aplastic anemia and 1 patient with megaloblastic anemia. MCV values > 100 fL and > 110 fL were more frequent in patients with megaloblastic anemia with most prominent anisopoikilocytosis, microcytosis and fragmented RBCs. Macrocytosis was noted in 35 (89.7%) patients with megaloblastic anemia and 12 (63.1%) with hypersplenism, 4 (50%) with aplastic anemia. Hypersegmented neutrophils were noted in the blood films of 36 (92.3%) patients with megaloblastic anemia. CONCLUSION: Megaloblastic anemia, hypersplenism and aplastic anemia are the common causes of pancytopenia in our study.