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Pharmaceutical Research Jul 2024Polysorbates are among the most used surfactants in biopharmaceutical products containing proteins. Our work aims to develop a high-throughput fluorometric assay to...
PURPOSE
Polysorbates are among the most used surfactants in biopharmaceutical products containing proteins. Our work aims to develop a high-throughput fluorometric assay to further diversify the analytical toolbox for quantification of PSs.
METHOD
The assay leverages the micelle activated fluorescence signal from N-Phenyl-1-Naphthylamine (NPN). The development and optimization of assay parameters were guided by the pre-defined analytical target profile. Furthermore, NMR was used to probe the interaction between protein, PS80 and NPN in the measurement system and understand protein interference.
RESULTS
All assay parameters including excitation and emission wavelengths, standard curve, NPN concentration, and incubation time have been optimized and adapted to a microplate format, making it compatible with automated solutions that will be pursued in the near future to drive consistency and efficiency in our workflows. The specificity, accuracy, and precision of the assay have been demonstrated through a case study. Furthermore, NMR results provided additional insight into the change of the interaction dynamics between PS80 and NPN as the protein concentration increases. The results indicate minimal interaction between the protein and PS80 at lower concentration. However, when the concentration exceeds 75 mg/mL, there is a significant interaction between the protein and PS-80 micelle and monomer.
CONCLUSION
A high-throughput fluorometric assay has been developed for quantification of polysorbates in biopharmaceutical samples including in-process samples, drug substance and drug product. The assay reported herein could serve as a powerful analytical tool for polysorbate quantification and control, complementing the widely used liquid chromatography with charged aerosol detection method.
PubMed: 38955997
DOI: 10.1007/s11095-024-03723-0 -
Archives of Toxicology Jul 2024Many fatal intoxications have been reported in connection with the consumption of newer, highly potent synthetic cannabinoids. Yet, a possible postmortem redistribution...
Does a postmortem redistribution affect the concentrations of the 7 azaindole-derived synthetic cannabinoid 5F-MDMB-P7AICA in tissues and body fluids following pulmonary administration to pigs?
Many fatal intoxications have been reported in connection with the consumption of newer, highly potent synthetic cannabinoids. Yet, a possible postmortem redistribution (PMR) might complicate reliable interpretation of analytical results. Thus, it is necessary to investigate the PMR-potential of new synthetic cannabinoids. The pig model has already proven to be suitable for this purpose. Hence, the aim of this study was to study the PMR of the synthetic cannabinoid 5F-MDMB-P7AICA and its main metabolite 5F-MDMB-P7AICA-dimethylbutanoic acid (DBA). 5F-MDMB-P7AICA (200 µg/kg body weight) was administered by inhalation to anesthetized and ventilated pigs. At the end of the experiment, the animals were euthanized and stored at room temperature for 3 days. Tissue and body fluid samples were taken daily. Specimens were analyzed after solid phase extraction using a standard addition method and LC-MS/MS, blood was quantified after protein precipitation using a validated method. In perimortem samples, 5F-MDMB-P7AICA was found mainly in adipose tissue, bile fluid, and duodenum contents. Small amounts of 5F-MDMB-P7AICA were found in blood, muscle, brain, liver, and lung. High concentrations of DBA were found primarily in bile fluid, duodenum contents, urine, and kidney/perirenal fat tissue. In the remaining tissues, rather low amounts could be found. In comparison to older synthetic cannabinoids, PMR of 5F-MDMB-P7AICA was less pronounced. Concentrations in blood also appear to remain relatively stable at a low level postmortem. Muscle, kidney, fat, and duodenum content are suitable alternative matrices for the detection of 5F-MDMB-P7AICA and DBA, if blood specimens are not available. In conclusion, concentrations of 5F-MDMB-P7AICA and its main metabolite DBA are not relevantly affected by PMR.
PubMed: 38955864
DOI: 10.1007/s00204-024-03815-1 -
Journal of Healthcare Quality Research Jul 2024
PubMed: 38955566
DOI: 10.1016/j.jhqr.2024.06.002 -
Bioconjugate Chemistry Jul 2024The chemical synthesis of homogeneously ubiquitylated histones is a powerful approach to decipher histone ubiquitylation-dependent epigenetic regulation. Among the...
The chemical synthesis of homogeneously ubiquitylated histones is a powerful approach to decipher histone ubiquitylation-dependent epigenetic regulation. Among the various methods, α-halogen ketone-mediated conjugation chemistry has recently been an attractive strategy to generate single-monoubiquitylated histones for biochemical and structural studies. Herein, we report the use of this strategy to prepare not only dual- and even triple-monoubiquitylated histones but also diubiquitin-modified histones. We were surprised to find that the synthetic efficiencies of multi-monoubiquitylated histones were comparable to those of single-monoubiquitylated ones, suggesting that this strategy is highly tolerant to the number of ubiquitin monomers installed onto histones. The facile generation of a series of single-, dual-, and triple-monoubiquitylated H3 proteins enabled us to evaluate the influence of ubiquitylation patterns on the binding of DNA methyltransferase 1 (DNMT1) to nucleosomes. Our study highlights the potential of site-specific conjugation chemistry to generate chemically defined histones for epigenetic studies.
PubMed: 38954775
DOI: 10.1021/acs.bioconjchem.4c00130 -
Journal of the American Chemical Society Jul 2024In light of recent conflicting reports regarding the hydroformylation catalytic activity derived from cationic Co(II) precatalysts of the form...
In light of recent conflicting reports regarding the hydroformylation catalytic activity derived from cationic Co(II) precatalysts of the form [Co(acac)(bis(phosphine))]BF, the synthetic procedures and characterization of [Co(acac)(dppBz)]BF, , are evaluated. Leveraging calibrated ESI-TOF MS methodologies, substantial quantities of Co(acac)(dppBz), , were observed within samples of . The source of the impurity, , is determined to derive from incomplete protonolysis of the Co(acac) precursor and ligand scrambling occurring during the synthesis of . Revised synthetic procedures using lower temperature conditions and longer reaction times afford analytically pure samples of based on ESI-TOF MS and NMR spectroscopic analysis. Complex is demonstrated to act as a hydroformylation precatalyst for the conversion of 1-hexene to 1-heptanal under relatively mild conditions at 51.7 bar and 140 °C. The presence of impurity is shown to dramatically decrease the catalytic performance derived from .
PubMed: 38954757
DOI: 10.1021/jacs.4c04239 -
ACS Applied Bio Materials Jul 2024In the realm of clinical applications, the concern surrounding biomedical device-related infections (BDI) is paramount. To mitigate the risk associated with BDI,...
In the realm of clinical applications, the concern surrounding biomedical device-related infections (BDI) is paramount. To mitigate the risk associated with BDI, enhancing surface characteristics such as lubrication and antibacterial efficacy is considered as a strategic approach. This study delineated the synthesis of a multifunctional copolymer, embodying self-adhesive, lubricating, and antibacterial properties, achieved through free radical polymerization and a carbodiimide coupling reaction. The copolymer was adeptly modified on the surface of stainless steel 316L (SS316L) substrates by employing a facile dip-coating technique. Comprehensive characterizations were performed by using an array of analytical techniques including Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, optical interferometry, scanning electron microscopy, and atomic force microscopy. Nanoscale tribological assessments revealed a notable reduction in the value of the friction coefficient of the copolymer-coated SS316L substrates compared to bare SS316L samples. The coating demonstrated exceptional resistance to protein adsorption, as evidenced in protein contamination models employing bovine serum albumin and fibrinogen. The bactericidal efficacy of the copolymer-modified surfaces was significantly improved against pathogenic strains such as and . Additionally, evaluations of blood compatibility and cellular compatibility underscored the remarkable anticoagulant performance and biocompatibility. Collectively, these findings indicated that the developed copolymer coating represented a promising candidate, with its facile modification approach, for augmenting lubrication and antifouling properties in the field of biomedical implant applications.
PubMed: 38954747
DOI: 10.1021/acsabm.4c00144 -
PloS One 2024The modified Benjamin-Bona-Mahony (mBBM) model is utilized in the optical illusion field to describe the propagation of long waves in a nonlinear dispersive medium...
The modified Benjamin-Bona-Mahony (mBBM) model is utilized in the optical illusion field to describe the propagation of long waves in a nonlinear dispersive medium during a visual illusion (Khater 2021). This article investigates the mBBM equation through the utilization of the rational [Formula: see text]-expansion technique to derive new analytical wave solutions. The analytical solutions we have obtained comprise hyperbolic, trigonometric, and rational functions. Some of these exact solutions closely align with previously published results in specific cases, affirming the validity of our other solutions. To provide insights into diverse wave propagation characteristics, we have conducted an in-depth analysis of these solutions using 2D, 3D, and density plots. We also investigated the effects of various parameters on the characteristics of the obtained wave solutions of the model. Moreover, we employed the techniques of linear stability to perform stability analysis of the considered model. Additionally, we have explored the stability of the associated dynamical system through the application of phase plane theory. This study also demonstrates the efficacy and capabilities of the rational [Formula: see text]-expansion approach in analyzing and extracting soliton solutions from nonlinear partial differential equations.
Topics: Models, Theoretical; Humans; Optical Illusions; Nonlinear Dynamics; Algorithms
PubMed: 38954709
DOI: 10.1371/journal.pone.0306196 -
PLOS Global Public Health 2024We assessed socioeconomic inequalities in social protection coverage among the public, men and women living with the human immunodeficiency virus (MLHIV, WLHIV), and...
We assessed socioeconomic inequalities in social protection coverage among the public, men and women living with the human immunodeficiency virus (MLHIV, WLHIV), and adolescent girls and young women (AGYW). We used population-based data from Cameroon, Côte d'Ivoire, Ethiopia, Eswatini, Kenya, Lesotho, Malawi, Namibia, Rwanda, Tanzania, Uganda, Zambia, and Zimbabwe. We constructed concentration curves (CC) and computed concentration indices (CIX) for each country and population group. A CC represents the cumulative percentage of social protection coverage plotted on the y-axis against the cumulative proportion of the population-ranked by socioeconomic status from the poorest to the richest-on the x-axis. The CIX quantifies the concentration of social protection coverage among the poor or the rich. The sample size ranged from 10,197 in Eswatini to 29,577 in Tanzania. Social protection coverage among the public varied from 5.2% (95% Confidence Interval 4.5%-6.0%) in Ethiopia to 39.9% (37.0%-42.8%) in Eswatini. It ranged from 6.9% (5.7%-8.4%) MLHIV in Zambia to 45.0% (41.2-49.0) among WLHIV in Namibia. Among AGYW, it varied from 4.4% (3.6-5.3) in Ethiopia to 44.6% (40.8-48.5) in Eswatini. Socioeconomic inequalities in social protection coverage favored the poor in 11/13 countries surveyed. It favored the rich in Cameroon and was undefined in Côte d'Ivoire. The CIX in these 11 countries ranged from -0.080 (p = 0.002) among the public in Malawi to -0.372 (p< 0.001) among WLHIV in Zimbabwe. In 8 of these 11 countries, ≥15% of people from the poorest households reported receiving social protection. Only in countries with higher levels of social protection coverage did most people from the poorest households achieve high coverage. Social protection coverage was low and favored the poor. Pro-poor social protection is insufficient to reach the poor. Research is required to reach the poorest households with social protection in Africa.
PubMed: 38954685
DOI: 10.1371/journal.pgph.0002973 -
PloS One 2024In this research, we employ the potent technique of Lie group analysis to derive analytical solutions for the (3+1)-extended Kadomtsev-Petviashvili (3D-EKP) equation....
In this research, we employ the potent technique of Lie group analysis to derive analytical solutions for the (3+1)-extended Kadomtsev-Petviashvili (3D-EKP) equation. The systematic application of this method enables the identification of Lie point symmetries associated with the equation, leading to the derivation of an optimal system of one-dimensional subalgebras relevant to the equation. This optimal system is utilized to obtain several invariant solutions. The Lie group method is subsequently applied to the reduced governing equations derived from the given equation. We complement our findings with Mathematica simulations illustrating some of the obtained solutions. Furthermore, a direct approach is used to investigate local conservation laws. Importantly, our study addresses a gap in the exploration of the 3D-EXP equation using group theoretic methods, making our findings novel in this context.
Topics: Algorithms; Models, Theoretical; Computer Simulation
PubMed: 38954677
DOI: 10.1371/journal.pone.0305177 -
IEEE Journal of Biomedical and Health... Jul 2024Magnetic resonance imaging (MRI)-based deep neural networks (DNN) have been widely developed to perform prostate cancer (PCa) classification. However, in real-world...
Magnetic resonance imaging (MRI)-based deep neural networks (DNN) have been widely developed to perform prostate cancer (PCa) classification. However, in real-world clinical situations, prostate MRIs can be easily impacted by rectal artifacts, which have been found to lead to incorrect PCa classification. Existing DNN-based methods typically do not consider the interference of rectal artifacts on PCa classification, and do not design specific strategy to address this problem. In this study, we proposed a novel Targeted adversarial training with Proprietary Adversarial Samples (TPAS) strategy to defend the PCa classification model against the influence of rectal artifacts. Specifically, based on clinical prior knowledge, we generated proprietary adversarial samples with rectal artifact-pattern adversarial noise, which can severely mislead PCa classification models optimized by the ordinary training strategy. We then jointly exploited the generated proprietary adversarial samples and original samples to train the models. To demonstrate the effectiveness of our strategy, we conducted analytical experiments on multiple PCa classification models. Compared with ordinary training strategy, TPAS can effectively improve the single- and multi-parametric PCa classification at patient, slice and lesion level, and bring substantial gains to recent advanced models. In conclusion, TPAS strategy can be identified as a valuable way to mitigate the influence of rectal artifacts on deep learning models for PCa classification.
Topics: Humans; Artifacts; Male; Prostatic Neoplasms; Magnetic Resonance Imaging; Rectum; Neural Networks, Computer; Image Interpretation, Computer-Assisted; Deep Learning
PubMed: 38954559
DOI: 10.1109/JBHI.2024.3384970