On the utility of predictive chromatography to complement mass spectrometry based intact protein identification

The amino acid sequence determines the individual protein three-dimensional structure and its functioning in an organism. Therefore, "reading" a protein sequence and determining its changes due to mutations or post-translational modifications is one of the objectives of proteomic experiments. The commonly utilized approach is gradient high-performance liquid chromatography (HPLC) in combination with tandem mass spectrometry. While serving as a way to simplify the protein mixture, the liquid chromatography may be an additional analytical tool providing complementary information about the protein structure. Previous attempts to develop "predictive" HPLC for large biomacromolecules were limited by empirically derived equations based purely on the adsorption mechanisms of the retention and applicable to relatively small polypeptide molecules. A mechanism of the large biomacromolecule retention in reversed-phase gradient HPLC was described recently in thermodynamics terms by the analytical model of liquid chromatography at critical conditions (BioLCCC). In this work, we applied the BioLCCC model to predict retention of the intact proteins as well as their large proteolytic peptides separated under different HPLC conditions. The specific aim of these proof-of-principle studies was to demonstrate the feasibility of using "predictive" HPLC as a complementary tool to support the analysis of identified intact proteins in top-down, middle-down, and/or targeted selected reaction monitoring (SRM)-based proteomic experiments

Real-world experience with netakimab in the treatment of spondyloarthritis

Aim. To study the real-world efficacy and safety of netakimab in the treatment of ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Materials and methods. The retrospective analysis included 23 patients (13 males; 56.5%) aged 23 to 73 years (median 42, interquartile range 28 to 52 years) with AS (n=12) or PsA (n=11) who received netakimab therapy from February 2021 to April 2023. Disease activity was assessed every 3-6 months based on the C-reactive protein (CRP) level for all patients according to the BASDAI and ASDAS-CRP indices for AS, DAPSA and PASI for PsA. These indicators were analyzed before therapy and at the last visit to assess the effectiveness of treatment. The results are presented as median (interquartile range). Results. In all patients treated with netakimab (median duration of treatment 11 months), the CRP level decreased from 10.6 (3.1; 17.3) to 3.1 (1.9; 8.9) mg/L (absolute difference -7.5 mg/L, median relative reduction -60%; p=0.008), and the proportion of patients with elevated CRP decreased from 70 to 41%; p=0.039. In patients with AS (median duration of treatment 9 months), BASDAI score decreased from 5.8 (4.7; 6.5) to 3.0 (1.9; 3.8) points (absolute difference -2.8 points, median relative reduction of -45%; p=0.008) and ASDAS-CRP score decreased from 2.8 (1.9; 3.9) to 1.9 (1.7; 2.6) points (absolute difference -0.9 points, median relative reduction -21%; p=0.007). The proportion of patients with high AS activity (BASDAI≥4) decreased from 90% to 20% (p=0.031); however, there was no significant change in the CRP level (absolute difference -4.9 mg/L, median relative reduction -57%; p=0.110). In patients with PsA (median duration of treatment 18 months), the CRP level decreased from 12.0 (4.5; 17.3) to 3.3 (2.0; 7.8) mg/L (absolute difference -8.7 mg/L, median relative reduction -80%; p=0.041), the DAPSA score decreased from 23.0 (19.0; 30.5) to 6.3 (5.2; 13.5) points (absolute difference -16.7 points, median relative reduction -69%; p=0.018). Three (13%) patients reported mild to moderate adverse events. Conclusion. The obtained data confirm the effectiveness and safety of netakimab in treating AS and PsA in real-world practice

Флотоекстракційне вилучення сполук урану(VІ) із розбавлених водних розчинів у присутності добавок електролітів

Purposefulness of the uranium(VI) flotoextraction isolation from their dilutednitrate, sulphate and carbonate solutions in the presence of electrolyte additions usingthe thin-emulsified solution of the trialkylamine in white spirit has been found.It has been shown that in the presence of electrolyte additions uranium compoundisolation degree decreased by 10—15%, optimal pH range got narrow and displacedto neutral medium, the collector optimal consumption decreased considerably, rateconstants increased into 1,5—2 times. High efficiency of the uranium(VI) flotoextraction isolation has been showed by tests carried out on carbonate and sulfatemodel solutions.Встановлено основні закономірності вилучення сполук урану(VI) методом флотоекстракції із сульфатних, нітратних і карбонатних розчинів у присутності добавок електролітів за допомогою тонкоемульгованого розчину триалкіламіну в уайт-спіриті. Показано, що в присутності електролітів ступінь вилучення сполук урану зменшується на 10—15 %, область оптимальних рН звужується та зміщується ближче до нейтральної, оптимальна витрата збирача суттєво зменшується, а константа швидкості зростає в 1,5—2 рази. Випробування з вилучення сполук урану з карбонатних і сульфатних модельних розчинів показали високу ефективність флотоекстракційного методу