Search

Titanium oxide nanoparticles (TiO 2 NPs) are currently used as ingredients in medicines and sunscreens. Unfortunately, recent information about TiO 2 NPs indicates their undesirable biological effect on colon cells. Therefore, the aim of this work was to synthesize and evaluate the physicochemical characterization of spherical (TiO 2 NSs) and rods-like (TiO 2 NRs) NPs, followed by assessment their cytotoxicity. For this purpose, both normal colon epithelial cells (CRL-1790) and cancerous colon cells (SW480) were used. Scanning transmission electron microscopy (STEM) showed that TiO 2 NSs with a diameter of ≈10 nm and TiO 2 NRs with the size of the longer axis ≈25 nm and shorter axis ≈3 nm were obtained. Based on the selected area electron diffraction (SAED) patterns, it was found that crystalline phases were obtained for both TiO 2 NPs. The UV-Vis spectra showed no contamination of TiO 2 NPs. Zeta potential values were 9.7 mV and 3.1 mV for NSs and NRs, respectively. Cytotoxicity of TiO 2 NPs was assessed using the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy-methoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium) test for various concentration of NPs. The cytotoxic effect for both TiO 2 NPs was visible for concentration of 75 μg/ml (for CRL-1790) and 50 μg/ml (for SW480) and higher, and it did not depend on the shape. Moreover, both types of TiO 2 NPs (in higher concentration) induce the generation of reactive oxygen species (ROS) in cells cultured with these NPs. Holotomographic microscopy studies showed increased cellular uptake of TiO 2 NPs by SW480. The obtained results for the synthesized TiO 2 NPs are a promising prospect for their use in biomedical application., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

New solid compounds of light lanthanide ions with 3-hydroxyflavone were synthesized in good yields (up to 85 %). The resulting complexes have been thoroughly characterized using various analytical and spectral techniques, including elemental analysis, complexometry, thermogravimetry, UV-VIS, FT-IR, 1 H NMR, 109 AgNPET LDI MS and fluorescence spectroscopy. The molecular formulas of the complexes were determined as follows: Ln(3HF) 3 , where 3HF-3-hydroxyflavone, Ln = La(III), Pr(III), Nd(III) and Ln(3HF) 3 ·nH 2 O, where n = 1 for Ln = Ce(III), Sm(III), Eu(III), and n = 2 for Gd(III). Thermogravimetric studies revealed that the water molecules in the hydrated compounds are located in the outer coordination sphere. Based on the spectral data, it was noted that lanthanide ions interacted with the 3OH and 4CO groups of 3-hydroxyflavone. The effect of lanthanide ion chelation on the excited-state intramolecular proton transfer (ESIPT) process and fluorescence emission of 3HF was investigated. It was found that coordination with metal ions can suppress the ESIPT process and enhance the fluorescence emission of 3HF. The synthesized compounds were also screened for their antibacterial activity, free radical scavenging capacity, and interaction with BSA. The results showed that the complexes exhibit higher biological activity compared to the ligand., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Brain tumors are among the most dangerous, due to their location in the organ that governs all life processes. Moreover, the high differentiation of these poses a challenge in diagnostics. Therefore, this study focused on the chemical differentiation of glioblastoma G4 (GBM) and two types of meningiomas (atypical - MAtyp and angiomatous - MAng) were done using Fourier Transform InfraRed (FTIR) spectroscopy, combined with statistical, multivariate, machine learning and rate of spectrum changes methods. The positions of all analyzed peaks differed between GBM and meningiomas. However, for two types of meningiomas, only shift of peaks corresponding to CH 2 bending vibrations, symmetric stretching vibrations of CH 2, amide A, amide I, CO lipids vibrations, asymmetric stretching vibrations of CH 3 were observed. Principal Component Analysis showed clear differentiation between GBM and the meningiomas. Decision tree clearly showed that wavenumbers corresponding to CO lipids vibrations provided the highest differentiation between GBM and meningiomas tissues, while amide I for two types of meningiomas. The accuracy and specificity of the results for GBM and meningiomas were more than 90 %, while for MAtyp and MAng, these parameters were around 80 %., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Magnetic resonance elastography (MRE) is a rapidly developing medical imaging technique that allows for quantitative assessment of the biomechanical properties of the tissue. MRE is now regarded as the most accurate noninvasive test for detecting and staging liver fibrosis. A two-dimensional (2D MRE) acquisition version is currently deployed at >2000 locations worldwide. 2D MRE allows for the evaluation of the magnitude of the complex shear modulus, also referred to as stiffness. The development of 3D vector MRE has enabled researchers to assess the biomechanical properties of small organs where wave propagation cannot be adequately analyzed with the 2D MRE imaging approach used in the liver. In 3D vector MRE, the shear waves are imaged and processed throughout a 3D volume and processed with an algorithm that accounts for wave propagation in any direction. Additionally, the motion is also imaged in x, y, and z directions at each voxel, allowing for more advanced processing to be applied., Purpose: This review describes the technical principles of 3D vector MRE, surveys its clinical applications in small organs, and discusses potential clinical significance of 3D vector MRE., Conclusion: 3D vector MRE is a promising tool for characterizing the biomechanical properties of small organs such as the uterus, pancreas, thyroid, prostate, and salivary glands. However, its potential has not yet been fully explored., Competing Interests: Declaration of competing interest The Mayo Clinic, R.L.E., and J.C. have intellectual property rights and a financial interest in magnetic resonance elastography technology. The remaining authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A design procedure for the separation of charge variants of a monoclonal antibody (mAb) was developed, which was based on the coupling of cation-exchange chromatography (CEX) and anion-exchange chromatography (AEX) under high loading conditions. The design of the coupled process was supported by a dynamic model. The model was calibrated on the basis of band profiles of variants determined experimentally for the mAb materials of different variant compositions. The numerical simulations were used to select the coupling configuration and the loading conditions that allowed for efficient separation of the mAb materials into three products enriched with each individual variant: the acidic (av), main (mv) and basic (bv) one. In the CEX section, a two-step pH gradient was used to split the loaded mass of mAb into a weakly bound fraction enriched with av and mv, and a strongly bound fraction containing the bv-rich product. The weakly bound fraction was further processed in the AEX section, where the mv-rich product was eluted in flowthrough, while the av-rich product was collected by a step change in pH. The choice of flow distribution and the number of columns in the CEX and AEX sections depended on the variant composition of the mAb material. For the selected configurations, the optimized mAb loading density in the CEX columns ranged from 10 to 26 mg mL -1 , while in the AEX columns it was as high as 300 or 600 mg mL -1 , depending on the variant composition of the mAb material. By proper selection of the loading condition, a trade-off between yield and purity of the products could be reached., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Endometriosis is a common disease with a complex pathomechanism and atypical symptoms, often leading to delayed diagnosis. Currently, the sole method for confirming the presence of the disease is through laparoscopy and histopathological examination of collected tissue. However, this invasive procedure carries potential risk and complications, necessitating the exploration of non-surgical diagnostic methods for endometriosis. This study aims to analyze peritoneal fluid and plasma samples for the expression of cathepsin L and cathepsin S to identify potential biomarkers for non-invasive diagnostic approaches to endometriosis., Material and Methods: In this cross-sectional study, plasma and peritoneal fluid samples were obtained during laparoscopy from 63 patients diagnosed with chronic pelvic pain or infertility. The study group consisted of women with confirmed endometriosis. The concentrations of cathepsins L and S were determined using an SPRi biosensor., Results: The study did not reveal significant differences in the concentrations of cathepsin L and cathepsin S between the control group and the study group, both in peritoneal fluid and plasma., Conclusions: Based on the results of this study, it appears that cathepsins L and S are not suitable candidates as biomarkers for endometriosis., Competing Interests: Declaration of competing interest The authors declare no conflicts of interests., (Copyright © 2024 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Background: Nemolizumab, an interleukin (IL)-31 receptor subunit α antagonist, inhibits the IL-31 pathway of itch and skin inflammation in atopic dermatitis. Two international phase 3 studies were done to assess the efficacy and safety of nemolizumab in atopic dermatitis. In this Article we report results for the 16-week initial treatment period of both trials., Methods: ARCADIA 1 and ARCADIA 2 were identical 48-week randomised, double-blind, placebo-controlled phase 3 trials in adult and adolescent participants (aged ≥12 years) with moderate-to-severe atopic dermatitis, associated pruritus, and inadequate response to topical steroids. Participants were enrolled from 281 clinics, hospitals, and academic centres in 22 countries across both trials, and were randomly assigned (2:1) to receive nemolizumab 30 mg subcutaneously (baseline loading dose 60 mg) or matching placebo once every 4 weeks with background topical corticosteroids (TCS) with or without topical calcineurin inhibitors (TCI; ie, TCS-TCI background treatment). Randomisation was done via interactive response technology and stratified by baseline disease and pruritus severity. Study staff and participants were masked throughout the study, with outcome assessors masked until database lock. Coprimary endpoints at week 16 post-baseline were Investigator's Global Assessment (IGA) success (score of 0 [clear skin] or 1 [almost clear skin] with a ≥2-point improvement from baseline) and at least 75% improvement in Eczema Area and Severity Index score from baseline (EASI-75 response). Outcome rates were compared between groups with the Cochran-Mantel-Haenszel test adjusting for randomisation strata. The key secondary endpoints were the proportion of participants with Peak Pruritus Numerical Rating Scale (PP-NRS) score improvement of at least 4 points at weeks 1, 2, 4, and 16; PP-NRS score below 2 at weeks 4 and 16; Sleep Disturbance Numerical Rating Scale score improvement of at least 4 points at week 16; EASI-75 response plus PP-NRS score improvement of at least 4 points at week 16; and IGA success plus PP-NRS score improvement of at least 4 points at week 16. Efficacy analyses were done on an intention-to-treat basis; safety analyses included all participants who received one dose of nemolizumab or placebo. Both studies are completed (ClinicalTrials.gov: ARCADIA 1, NCT03985943 and ARCADIA 2, NCT03989349)., Findings: Between Aug 9, 2019, and Nov 2, 2022, 1728 participants were enrolled across both trials: 1142 were allocated to nemolizumab plus TCS-TCI (620 in ARCADIA 1 and 522 in ARCADIA 2) and 586 to placebo plus TCS-TCI (321 in ARCADIA 1 and 265 in ARCADIA 2). ARCADIA 1 included 500 (53%) male participants and 441 (47%) female participants, and ARCADIA 2 included 381 (48%) male participants and 406 (52%) female participants. Mean age ranged from 33·3 (SD 15·6) years to 35·2 (17·0) years across the treatment groups. Both trials met the coprimary endpoints; at week 16, a greater proportion of participants receiving nemolizumab plus TCS-TCI versus placebo plus TCS-TCI had IGA success (ARCADIA 1: 221 [36%] of 620 vs 79 [25%] of 321, adjusted percentage difference 11·5% [97·5% CI 4·7-18·3], p=0·0003; ARCADIA 2: 197 [38%] of 522 vs 69 [26%] of 265, adjusted difference 12·2% [4·6-19·8], p=0·0006) and an EASI-75 response (ARCADIA 1: 270 [44%] vs 93 [29%], adjusted difference 14·9% [7·8-22·0], p<0·0001; ARCADIA 2: 220 [42%] vs 80 [30%], adjusted difference 12·5% [4·6-20·3], p=0·0006). Significant benefits were observed with nemolizumab for all key secondary endpoints including improvement in itch, as early as week 1, and sleep improvement by week 16. The safety profile was similar between nemolizumab plus TCS-TCI and placebo plus TCS-TCI. In the safety sets, 306 (50%) of 616 participants (ARCADIA 1) and 215 (41%) of 519 participants (ARCADIA 2) who received nemolizumab plus TCS-TCI had at least one treatment-emergent adverse event (serious treatment-emergent adverse events in six [1%] and 13 [3%], respectively); and 146 (45%) of 321 (ARCADIA 1) and 117 (44%) of 263 (ARCADIA 2) who received placebo plus TCS-TCI had at least one treatment-emergent adverse event (serious treatment-emergent adverse events in four [1%] and three [1%], respectively). Ten serious treatment-emergent adverse events possibly related to nemolizumab were reported in five (1%) participants in ARCADIA 2. No deaths occurred., Interpretation: Nemolizumab plus TCS-TCI was efficacious and showed statistically and clinically significant improvements in inflammation and itch in adults and adolescents with moderate-to-severe atopic dermatitis. Nemolizumab might offer a valuable extension of current therapies if approved., Funding: Galderma., Competing Interests: Declaration of interests JIS has received honoraria as a consultant or advisory board member for AbbVie, Aldena, Amgen, AOBiome, Arcutis, Arena, Asana, Aslan, Attovia, BiomX, Biosion, Bodewell, Boehringer-Ingelheim, Bristol Myers Squibb, Cara, Castle Biosciences, Celgene, Connect Biopharma, Corevitas, Dermavant, Eli Lilly, Galderma, GSK, Incyte, Kiniksa, LEO Pharma, MyOr Diagnostics, Nektar, Novartis, Optum, Pfizer, RAPT Therapeutics, Recludix, Regeneron, Sanofi-Genzyme, Shaperon, Target RWE, and Union Therapeutics; and his institution has received grants from Galderma, Incyte, and Pfizer. AW has received grants or contracts from AbbVie, Aileens, Almirall, Amgen, Beiersdorf, Bioderma, BioProject, Bristol Myers Squibb, Chugai, Galapagos, Galderma, Glenmark, GSK, Hans Karrer, Janssen, Maruho, MedImmune, MSD, Mylan, Novartis, Pfizer, Pierre Fabre, Regeneron, Sandoz, Sanofi-Aventis, and UCB; payment or honoraria from AbbVie, Aileens, Almirall, Amgen, Beiersdorf, Bioderma, Galderma, Glenmark, LEO Pharma, L'Oreal, Maruho, Novartis, Pfizer, Pierre Fabre, Regeneron, Sanofi-Aventis, and UCB; and support for attending meetings or travel from AbbVie, LEO Pharma, and Pierre Fabre. He has also participated on a data safety monitoring board or advisory board for Alentis Therapeutics and BioProject; served as Secretary and Executive Board member of the International Society of Atopic Dermatitis and Vice Chair of the European Task Force on Atopic Dermatitis; and received medical writing support for clinical trial reports from AbbVie, Almirall, Galderma, LEO Pharma, Eli Lilly, L'Oreal, Merck, Novartis, Pfizer, Pierre Fabre, Regeneron, Sanofi-Aventis, and UCB. AR has served as an investigator or participated in advisory boards for AbbVie, Alvotech, Amgen, AnaptysBio, Biotherapy, Bristol Myers Squibb, Celgene, Celltrion, Dermira, Galderma, Inflarx, Janssen, Kiniksa, Kymab, LEO Pharma, Novartis, Pierre Fabre, Pfizer, Trevi Therapeutics, and UCB; and has received honoraria from Chema Rzeszow, Eli Lilly, LEO Pharma, Novartis, Sandoz, and Takeda. DT is a lecturer or consultant for AbbVie, Almirall, Amgen, Boehringer-Ingelheim, Bristol Myers Squibb, Celltrion, Galderma, Janssen-Cilag, Kyowa Kirin, LEO Pharma, Eli Lilly, Novartis, Regeneron, Sandoz, Target RWE, and UCB; and has received grants from AbbVie, LEO Pharma, and Novartis (paid to his institution). FJL has received honoraria as a consultant, advisory board member, or speaker for Almirall, Celgene, Eli Lilly, Galderma, Menlo Therapeutics, Novartis, Pelpharma, Pfizer, Sanofi, Trevi Therapeutics, and Vifor Pharma; has received support for participating in scientific meetings from Amgen, AbbVie, Celgene, Eli Lilly, Galderma, Janssen-Cilag, LEO Pharma, Novartis, Pelpharma, Pfizer, and Sanofi; and has served as the principal investigator in clinical studies for Amgen, Almirall, DS Biopharma, Eli Lilly, Galderma, Incyte, Kiniksa, Menlo Therapeutics, LEO Pharma, Pfizer, and Trevi Therapeutics. KAP has served as a consultant, scientific advisor, investigator, scientific officer, or speaker for Pfizer, AbbVie, Acelyrin, Akros, Alumis, Amgen, Arcutis, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Can-Fite BioPharma, Celltrion, Concert Pharmaceuticals, CorEvitas, Dermavant, Dermira, Dice Pharmaceuticals, Dice Therapeutics, Eli Lilly, Evelo Biosciences, Forbion, Galderma, Horizon Therapeutics, Incyte, Janssen, Kymab, Kyowa Hakka Kirin, LEO Pharma, Meiji Seika Pharma, Mitsubishi Pharma, Nimbus Therapeutics, Novartis, Reistone, Sandoz, Genzyme (subsidiary of Sanofi Aventis), Sun Pharma, Takeda, Tarsus Pharmaceuticals, UCB, and Zai Lab. LSG has received grants, contracts, consulting fees, payment, or honoraria for scientific or educational work from Galderma, AbbVie, Pfizer, Incyte, Arcutis, LEO Pharma, Dermavan, and Eli Lilly; and is an investigator for Allergan and Galderma. J-DB has received speaker fees from AbbVie, AstraZeneca, Galderma, Janssen, LEO Pharma, Eli Lilly, Novartis, Pfizer, and Sanofi, consulting fees from Eli Lilly and Neovacs, a research grant from Astra Zeneca, Sanofi, and Therakos, and travel grants from AbbVie, Janssen, and Sanofi; and has served on a data safety monitoring board or advisory board for AbbVie, AstraZeneca, Galderma, Janssen, LEO Pharma, Eli Lilly, Novartis, Pfizer, and Sanofi. AEP has received grants or contracts from Amgen, Medac Pharma, and Pfizer, acted as an investigator, speaker, and advisor for or received educational support or research funding from Sanofi, Eli Lilly, Pfizer, LEO Pharma, AbbVie, Galderma, Novartis, Janssen, Boehringer Ingelheim, Bristol Myers Squibb, UCB, Amgen, Almirall, Artax Biopharma, and Medac Pharma. JMC has received honoraria as a consultant, advisory board member, or speaker, or has served as the principal investigator in clinical studies, for Almirall, Celgene, Eli Lilly, Galderma, Novartis, Pfizer, Sanofi, Amgen, AbbVie, Janssen-Cilag, LEO Pharma, UCB, Boehringer Ingelheim, Bristol Myers Squibb, and Sandoz. BR has served as an investigator for Galderma. JCS has received consulting fees or honoraria from Galderma, AbbVie, Almirall, Eli Lilly, Janssen, LEO Pharma, Novartis, Pierre-Fabre, Pfizer, Sanofi-Genzyme, Trevi, and UCB; has served as President of the Polish Dermatological Society; and has served as an investigator for AbbVie, Amgen, Bristol Myers Squibb, Galapagos, Galderma, Incyte, InflaRx, Janssen, Kliniksa, Kymab, Menlo Therapeutics, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Trevi Therapeutics, and UCB Pharma. DK has served as an investigator for Galderma. BH is an investigator for Galderma. MK has served as an investigator for Galderma. NM is a consultant or speaker for AbbVie, Almirall, Apogee, Boehringer Ingelheim, Bristol Myers Squibb, Dr Wolff, Eli Lilly, La Roche-Posay, LEO Pharma, Novartis, Pfizer, Sanofi, and UCB; and has served as an investigator for Galderma. SP has served as an investigator for Galderma. NN has served as an investigator for Galderma. MBS has received honoraria as a consultant, advisory board member, or speaker from Amgen, AbbVie, Arcutis, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Galderma, Incyte Pharma, Janssen, L'Oréal Canada, LEO Pharma, Merck, Novartis, Pfizer, Sanofi, Sun Pharmaceuticals, and UCB Canada; support for attending meetings or travel from Galderma, Janssen, and Pfizer; has served as the principal investigator in clinical studies for Alumis, Amgen, AbbVie, Bristol Myers Squibb, Dermavant, Evelo, Galderma, Inycte, Janssen, LEO Pharma, Meiji Pharma, Moberg Pharma, Novartis, Pfizer, Reistone Biopharma, Sanofi, and Ventyx Biosciences; and is Treasurer for the Canadian Dermatology Association, Treasurer for the Ontario Medical Association section of Dermatology, and Secretary for the Dermatology Association of Ontario. VJ has consulted or advised for or received research funding for speakers bureaus from Pediapharm, Aralez, Sanofi, Regeneron, Bausch, Novartis, Medexus, ALK-Abelló, Celgene, LEO Pharma, Mylan, Amgen, AbbVie, Pfizer, AstraZeneca, GSK, Covis Pharma, and Incyte; and has received research grants from Eli Lilly, Pfizer, Galderma, AstraZeneca, Arcutis, Sanofi, LEO Pharma, Amgen, AbbVie, GSK, Allakos, Novartis, Janssen, and Kymab. KP has served as an investigator for Galderma. SYC, PFM, LU, and CP are employees of Galderma., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Polylactic acid (PLA), a polymer derived from renewable resources, is gaining increasing attention in the development of biomedical devices due to its cost-effectiveness, low immunogenicity, and biodegradability. However, its inherent hydrophobicity remains a problem, leading to poor cell adhesion features. On this basis, the aim of this work was to develop a method for functionalizing the surface of PLA films with a biopolymer, chitosan (CH), which was proved to be a material with intrinsic cell adhesive properties, but whose mechanical properties are insufficient to be used alone. The combination of the two polymers, PLA as a bulk scaffold and CH as a coating, could be a promising combination to develop a scaffold for cell growth. The modification of PLA films involved several steps: aminolysis followed by bromination to graft amino and then bromide groups, poly(glycidyl methacrylate) (PGMA) grafting by surface-initiated supplemental activator and reducing agent atom transfer radical polymerization (SI-SARA ATRP) and finally the CH grafting. To prove the effective adhesive properties, conjugated and non-conjugated films were tested in vitro as substrates for neuronal cell growth using differentiated neurons from human induced pluripotent stem cells. The results demonstrated enhanced cell growth in the presence of CH., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The aim of this article is to apply advanced predictive modeling techniques to understand the degradation process of microplastics in aquatic environments. Utilizing a Fractional Factorial Central Composite Experimental Plan, this study seeks to develop precise predictive statistical models that enable forecasting the quantity of pollutants generated during the degradation of microplastics under various environmental conditions. This tool was applied to model changes in DOC (dissolved organic carbon) and DEHP (bis(2-ethylhexyl) phthalate) values during the degradation of microplastics in aquatic ecosystems. The methods were developed using data derived from laboratory tests conducted using the GC-MS technique. The obtained approximating functions, considering factors such as degradation time, water temperature, and particle size, significantly reduced the analysis time. A two-stage verification of the approximating functions was conducted, considering the accuracy of the function form, its adequacy, the statistical significance of input variables, and their correlation with DOC and DEHP. The employed a Fractional Factorial Central Composite Experimental Plan allowed for the simultaneous reduction in the number of experiments and prediction of the influence of variables on the output values. Precise predictive models support understanding of the microplastic degradation process, facilitating the development of effective strategies for managing this pollution., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Financed by the Minister of Science and Higher Education Republic of Poland within the program "Regional Excellence Initiative”. This publication reflects the implementation of Research Project No. 2022/06/X/ST5/00624, ID: 556207 funded by the Polish National Science Center., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The annular pancreas (AP) is a rare gastrointestinal congenital malformation, in which malrotation of the pancreatic ventral bud in the seventh week of embryonic development manifests in a partial or complete ring of tissue around the second part of the duodenum., Methods: The main online medical databases such as PubMed, ScienceDirect, Wiley online library, Web of Science, and EBSCO discovery service were used to gather all relevant studies on the AP., Results: A total of 12,729,118 patients were analyzed in relation to the prevalence of AP. The pooled prevalence of AP was 0.0045% (95% CI: 0.0021%-0.0077%). The most frequent comorbidity in adults and children was duodenal obstruction, with a pooled prevalence of 24.04% and 52.58%, respectively (95% CI: 6.86%-46.48% and 35.56%-69.31%, respectively). The most frequent operation in adult patients with AP was duodenojejunostomy, with pooled prevalence established at 3.62% (95% CI: 0.00%-10.74%)., Conclusion: The diagnostic complexity of AP is accentuated by its nonspecific clinical symptoms, making accurate identification reliant on imaging studies. Therefore, having a thorough knowledge of the clinical characteristics of the AP and its associated anomalies becomes paramount when faced with this rare congenital condition., (Copyright © 2024 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

The dynamic price increases of fertilizers and the generation of organic waste are currently global issues. The growth of the population has led to increased production of solid municipal waste and a higher demand for food. Food production is inherently related to agriculture and, to achieve higher yields, it is necessary to replenish the soil with essential minerals. A synergistic approach that addresses both problems is the implementation of the composting process, which aligns with the principles of a circular economy. Food waste, green waste, paper waste, cardboard waste, and animal manure are promising feedstock materials for the extraction of valuable compounds. This review discusses key factors that influence the composting process and compares them with the input materials' parameters. It also considers methods for optimizing the process, such as the use of biochar and inoculation, which result in the production of the final product in a significantly shorter time and at lower financial costs. The applications of composts produced from various materials are described along with associated risks. In addition, innovative composting technologies are presented., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The influence of mobile phase composition on the efficiency of enantiomer separation by achiral chromatography (ACh) was investigated. The separation was induced by the phenomenon of self-disproportionation of enantiomers (SDE) triggered by their homo and hetero-chiral interactions in an achiral environment. Typically, SDE occurs in apolar mobile phases of weak elution strength, which causes the separation time to extend and the process productivity to deteriorate. To mitigate that effect, we altered the content of a strong solvent (modifier) in the mobile phase by use of a solvent gradient in which the target enantiomer was separated in the presence of the weak solvent, whereas the unresolved mixture of enantiomers was eluted by increasing the modifier content in the mobile phase. This enabled accelerating the solute elution while preserving the separation selectivity. The approach was examined for the separation of nonracemic mixtures of two structurally different compounds that exhibited the SDE effect in ACh, i.e., metalaxyl (MX) and methyl p-tolyl sulfoxide (MTSO). The target compound of the separation was the more abundant enantiomer in the enantiomeric mixture. The process realization was preceded by the determination of the effect of the modifier content on the separation yield for enantiomeric mixtures of MX and MTSO of different enantiomeric excess (ee). In the case of MX, yield of the pure target enantiomer varied from 2 %, for the maximum concentration of the modifier, to 45 % for the minimum modifier concentration and the largest ee used in the experiments. In the case of MTSO, the yield varied from minimum 40 % to maximum 66 %. To predict the process, we employed a dynamic model, in which underlying thermodynamic dependencies were implemented., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

The aim of the work was to assess the usefulness of machine learning in predicting the migration of pollutants from microplastics. The search for methods to reduce unnecessary laboratory analyzes is a necessary action both to protect the environment and from an economic perspective. Multiple regression, artificial neural networks, support vector method and random forest regression were used in the study to predict leaching of plasticizers and other contaminants from microplastics. The development of the methods were based on the results of laboratory tests obtained by the GC-MS method. The results obtained confirm the potential of artificial neural networks and the support vector method for effective modelling and prediction of chemical compounds leached from microplastics. Correlation results were obtained for the analyzed parameters between the data obtained in the model and laboratory data in the range of 0.96-0.98 and 0.93-0.99 for artificial neural networks and the support vector method, respectively. Multiple regression showed the lowest performance in all cases in predicting plastic phthalic acid esters (coefficient of determination (R 2 ) in the range of 0.03-0.24). ENVIRONMENTAL IMPLICATION: The results presented in this paper will provide new insight into the influence of different parameters and factors on the leaching of plastic additives. This information is necessary to assess the harmfulness of these materials. The collected data is unique on a global scale. For the first time, machine learning were used to predict the leaching rate of plasticizers from different polymers under different environmental conditions. The use of machine learning allows to reduce unnecessary laboratory tests and reduce costs and protect the environment. Currently, there are no research results in this field in the scientific literature., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This publication reflects the implementation of Research Project No. 2019/03/X/ST10/01557 funded by Poland’s National Science Centre. The research leading to these results has received funding from the commissioned task entitled "VIA CARPATIA Universities of Technology Network named after the President of the Republic of Poland Lech Kaczyński” contract no. MEiN/2022/DPI/2578 action entitled "In the neighborhood - inter-university research internships and study visits.”, (Copyright © 2023 Elsevier B.V. All rights reserved.)

The objective of this article was to assess the effectiveness of simulation models in predicting the emission of additives from microplastics. The variety of plastics, their chemical structure, physicochemical properties, as well as the influence of environmental factors on their decomposition generate countless cases for analysis in the laboratory. The search for methods to reduce unnecessary laboratory analyses is a necessary action to protect the environment and ensure economic efficiency. In this study, machine learning techniques, specifically the methodology of artificial neural networks (ANNs), were employed to predict the leaching of contaminants from microplastics. The network's development was based on laboratory test results obtained using gas chromatography coupled to a mass spectrometer (GC-MS). The conducted research revealed the significant utility of the multilayer perceptron (MLP) - type networks, which exhibited correlation levels exceeding 95 % for various predicted values. One comprehensive ANN was developed, encompassing all the parameters analyzed, alongside individual networks for each parameter. A common network for all factors enabled for satisfactory results. Temperature and holding time had the greatest influence on the values of parameters such as the electrolytic conductivity of water (EC), dissolved organic carbon (DOC), and di(2-ethylhexyl) phthalate (DEHP). Correlation results ranged from 0.94 to 0.99 for EC, DEHP and DOC between the model data and laboratory data in each set of training, test, and validation data. The conducted research demonstrated that ANNs are a valuable machine learning method for analyzing and predicting pollutant emissions during the decomposition of microplastics., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This publication reflects the implementation of Research Project No. 2019/03/X/ST10/01557 funded by the Polish National Science Center. The research leading to these results has received funding from the commissioned task entitled “VIA CARPATIA Universities of Technology Network named after the President of the Republic of Poland Lech Kaczyński” contract no. MEiN/2022/DPI/2578 action entitled “In the neighborhood - inter-university research internships and study visits.”, (Copyright © 2023 Elsevier B.V. All rights reserved.)

Primary myelofibrosis (PM) is a myeloproliferative neoplasm characterized by stem cell-derived clonal neoplasms. Several factors are involved in diagnosing PM, including physical examination, peripheral blood findings, bone marrow morphology, cytogenetics, and molecular markers. Commonly gene mutations are used. Also, these gene mutations exist in other diseases, such as polycythemia vera and essential thrombocythemia. Hence, understanding the molecular mechanism and finding disease-related biomarker characteristics only for PM is crucial for the treatment and survival rate. For this purpose, blood samples of PM (n = 85) vs. healthy controls (n = 45) were collected for biochemical analysis, and, for the first time, Fourier Transform InfraRed (FTIR) spectroscopy measurement of dried PM and healthy patients' blood serum was analyzed. A Support Vector Machine (SVM) model with optimized hyperparameters was constructed using the grid search (GS) method. Then, the FTIR spectra of the biomolecular components of blood serum from PM patients were compared to those from healthy individuals using Principal Components Analysis (PCA). Also, an analysis of the rate of change of FTIR spectra absorption was studied. The results showed that PM patients have higher amounts of phospholipids and proteins and a lower amount of H-O=H vibrations which was visible. The PCA results indicated that it is possible to differentiate between dried blood serum samples collected from PM patients and healthy individuals. The Grid Search Support Vector Machine (GS-SVM) model showed that the prediction accuracy ranged from 0.923 to 1.00 depending on the FTIR range analyzed. Furthermore, it was shown that the ratio between α-helix and β-sheet structures in proteins is 1.5 times higher in PM than in control people. The vibrations associated with the CO bond and the amide III region of proteins showed the highest probability value, indicating that these spectral features were significantly altered in PM patients compared to healthy ones' spectra. The results indicate that the FTIR spectroscope may be used as a technique helpful in PM diagnostics. The study also presents preliminary results from the first prospective clinical validation study., Competing Interests: Declaration of Competing Interest The authors declare that they have no affiliations with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in this manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Rapid and accurate diagnosis of any illness determines the success of treatment. The same applies to multiple sclerosis (MS), chronic, inflammatory, and neurodegenerative diseases (ND) of the central nervous system (CNS). Unfortunately, the definitive diagnosis of MS is prolonged and involves mainly clinical symptoms observation and magnetic resonance imaging (MRI) of the CNS. However, as we previously reported, Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy shed new light on the minimally invasive, label-free, and rapid diagnosis of this illness through blood fraction. Herein we introduce Raman spectroscopy coupled with chemometric analysis to provide more detailed information about the biochemical changes behind MS. This pilot study demonstrates that mentioned combination may provide a new diagnostic biomarker and bring closer to rapid MS diagnosis. It has been shown that Raman spectroscopy provides lipid and carotenoid molecules as useful biomarkers which may be applied for both diagnosis and treatment monitoring., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Primary myelofibrosis (PM) is one of the myeloproliferative neoplasm, where stem cell-derived clonal neoplasms was noticed. Diagnosis of this disease is based on: physical examination, peripheral blood findings, bone marrow morphology, cytogenetics, and molecular markers. However, the molecular marker of PM, which is a mutation in the JAK2V617F gene, was observed also in other myeloproliferative neoplasms such as polycythemia vera and essential thrombocythemia. Therefore, there is a need to find methods that provide a marker unique to PM and allow for higher accuracy of PM diagnosis and consequently the treatment of the disease. Continuing, in this study, we used Raman spectroscopy, Principal Components Analysis (PCA), and Partial Least Squares (PLS) analysis as helpful diagnostic tools for PM. Consequently, we used serum collected from PM patients, which were classified using clinical parameters of PM such as the dynamic international prognostic scoring system (DIPSS) for primary myelofibrosis plus score, the JAK2V617F mutation, spleen size, bone marrow reticulin fibrosis degree and use of hydroxyurea drug features. Raman spectra showed higher amounts of C-H, C-C and C-C/C-N and amide II and lower amounts of amide I and vibrations of CH 3 groups in PM patients than in healthy ones. Furthermore, shifts of amides II and I vibrations in PM patients were noticed. Machine learning methods were used to analyze Raman regions: (i) 800 cm -1 and 1800 cm -1 , (ii) 1600 cm -1 -1700 cm -1 , and (iii) 2700 cm -1 -3000 cm -1 showed 100 % accuracy, sensitivity, and specificity. Differences in the spectral dynamic showed that differences in the amide II and amide I regions were the most significant in distinguishing between PM and healthy subjects. Importantly, until now, the efficacy of Raman spectroscopy has not been established in clinical diagnostics of PM disease using the correlation between Raman spectra and PM clinical prognostic scoring. Continuing, our results showed the correlation between Raman signals and bone marrow fibrosis, as well as JAKV617F. Consequently, the results revealed that Raman spectroscopy has a high potential for use in medical laboratory diagnostics to quantify multiple biomarkers simultaneously, especially in the selected Raman regions., Competing Interests: Declaration of competing interest There are no conflicts of interest in this study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The polymeric cytisine-enriched fibers based on poly(3-hydroxybutyrate) were obtained using electrospinning method. The biocompatibility study, advanced thermal analysis and release of cytisine from the poly(3-hydroxybutyrate) fibers were carried out. The nanofibers' morphology was evaluated by scanning electron microscopy. The formation and description of phases during the thermal processes of fibers by the advanced thermal analysis were examined. The new quantitative thermal analysis of polymeric fibers with cytisine phases based on vibrational, solid and liquid heat capacities was presented. The apparent heat capacity of fibers was measured using the standard differential scanning calorimetry. The quantitative analysis allowed for the study of the glass transition and melting/crystallization process. The mobile amorphous fraction, degree of crystallinity and rigid amorphous fraction were determined depending on the thermal history of semicrystalline polymeric fibers. Furthermore, the cytisine dissolution behaviour was studied. It was observed that the kinetic of the release from polymeric nanofiber is delayed than for the marketed product. The immunosafety of the tested polymeric nanofibers with cytisine was confirmed by the Food and Drug Agency Guidance as well as the European Medicines Agency. The polymeric matrix with cytisine seems to be a promising candidate for the prolonged release formulation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Anna Czerniecka-Kubicka reports financial support was provided by National Science Centre, Poland. Vladimir Sedlarik reports financial support was provided by Ministry of Education, Youth and Sports of the Czech Republic., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The acidic charge variants (av) of monoclonal antibodies (mAb) are often reported to have reduced therapeutic potency compared with the main (mv) and basic variants (bv), therefore reduction in the av content in mAb pools is often prioritized over reduction in the bv content. In previous studies we described two different methods for reducing the av content, which were based on either ion exchange chromatography or selective precipitation in polyethylene glycol (PEG) solutions. In this study, we have developed a coupled process, in which advantages of simplicity and ease in realization of PEG-aided precipitation and high separation selectivity of anion exchange chromatography (AEX) were exploited. The design of AEX was supported by the kinetic-dispersive model, which was supplemented with the colloidal particle adsorption isotherm, whereas the precipitation process and its coupling with AEX was quantified by simple mass balance equations and underlying thermodynamic dependencies. The model was used to assess the performance of the coupling of AEX and precipitation under different operating conditions. The advantage of the coupled process over the stand-alone AEX depended on the demand for the av reduction as well as the initial variant composition of the mAb pool, e.g., the improvement in the throughput provided by the optimized sequence of AEX and PREC varied from 70 to 600% for the initial av content changed from 35 to 50% w/w, and the reduction demand changed from 30 to 60%., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Three new solid lanthanide complexes with nalidixic acid (HNal) with the stoichiometry [Ln(Nal) 3 ]·5·.5H 2 O (Ln = Tb, Dy and Ho) were synthesized applying the green synthesis method from the aqueous solutions without the organic solvent addition and fully characterized by the elemental analysis, XRF, complexometric titration, gravimetric analysis, molar conductivity and solubility measurements, powder X-Ray diffraction, UV-Vis and infrared (FT-IR) spectroscopies. Moreover, the luminescent properties of the Tb(III), Dy(III), and Ho(III) complexes in the solid state and in the solutions were investigated. On the basis of the detailed spectral analysis, it was concluded that the nalidixate ligands bind to the lanthanide ions by the bidentate carboxylate and carbonyl groups while water molecules belong to the outer coordination sphere. At the excitation of UV light, the complexes exhibited characteristic emission of central lanthanide ions, the intensity of which depends significantly on the excitation wavelength and/or the solvent. Thus, the application of nalidixic acid (apart from biological activity) for the synthesis of luminescent lanthanide complexes was confirmed which can find potential applications in the field of photonic devices and/or bioimaging agents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This study aimed to develop a novel approach for diagnosing Polycythemia Vera (PV), a stem cell-derived neoplasm of the myeloid lineage. The approach utilized Raman spectroscopy coupled with multivariate analysis to analyze blood serum samples collected from PV patients. The results showed that PV serum exhibited lower protein and lipid levels and structural changes in the functional groups that comprise proteins and lipids. The study also demonstrated differences in lipid biosynthesis and protein levels in PV serum. Using the Partial Least Square Discriminant Analysis (PLS-DA) model, Raman-based multivariate analysis achieved high accuracy rates of 96.49 and 93.04% in the training sets and 93.10% and 89.66% in the test sets for the 800-1800 cm -1 and 2700-3000 cm -1 ranges, respectively. The area under the curve (AUC) values of the test datasets were calculated as 0.92 and 0.89 in the 800-1800 cm -1 and 2700-3000 cm -1 spectral regions, respectively, demonstrating the effectiveness of the PLS-DA models for the diagnosis of PV. This study highlights the potential of Raman spectroscopy-based analysis in the early and accurate diagnosis of PV, enabling the application of effective treatment strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no affiliations with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in this manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The phenomenon of partial separation of enantiomeric mixtures in achiral chromatography (ACh) has already been documented for a wide variety of chiral compounds. It is attributed to the so-called effect of self-disproportionation of enantiomers (SDE). However, quantitative description of the SDE mechanism underlying adsorption of enantiomers on achiral surfaces is still incomplete, which hinders the application of that technique for large-scale separations. In this study, a mechanistic model for description of retention behavior of SDE-phoric compounds in silica-based ACh has been developed along with a procedure for fast determination of the model parameters. The model assumes formation of associates of chiral molecules, which occurs due to homo and hetero-chiral interactions in the adsorbed phase. The ability of the model to reproduce band profiles was verified for enantiomeric mixtures of three structurally different chiral compounds., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Few therapeutic options are available for patients with moderate-to-severe hidradenitis suppurativa. We aimed to assess the efficacy of secukinumab in patients with moderate-to-severe hidradenitis suppurativa in two randomised trials., Methods: SUNSHINE and SUNRISE were identical, multicentre, randomised, placebo-controlled, double-blind phase 3 trials done in 219 primary sites in 40 countries. Patients aged 18 years old or older with the capacity to provide written informed consent and with moderate-to-severe hidradenitis suppurativa (defined as a total of ≥5 inflammatory lesions affecting ≥2 distinct anatomical areas) for at least 1 year were eligible for inclusion. Included patients also agreed to daily use of topical over-the-counter antiseptics on the areas affected by hidradenitis suppurativa lesions while on study treatment. Patients were excluded if they had 20 or more fistulae at baseline, had ongoing active conditions requiring treatment with prohibited medication (eg, systemic biological immunomodulating treatment, live vaccines, or other investigational treatments), or met other exclusion criteria. In both trials, patients were randomly assigned (1:1:1) by means of interactive response technology to receive subcutaneous secukinumab 300 mg every 2 weeks, subcutaneous secukinumab 300 mg every 4 weeks, or subcutaneous placebo all via a 2 mL prefilled syringe in a double-dummy method as per treatment assignment. The primary endpoint was the proportion of patients with a hidradenitis suppurativa clinical response, defined as a decrease in abscess and inflammatory nodule count by 50% or more with no increase in the number of abscesses or in the number of draining fistulae compared with baseline, at week 16, assessed in the overall population. Hidradenitis suppurativa clinical response was calculated based on the number of abscesses, inflammatory nodules, draining fistulae, total fistulae, and other lesions in the hidradenitis suppurativa affected areas. Safety was assessed by evaluating the presence of adverse events and serious adverse events according to common terminology criteria for adverse events, which were coded using Medical Dictionary for Regulatory Activities terminology. Both the SUNSHINE, NCT03713619, and SUNRISE, NCT03713632, trials are registered with ClinicalTrials.gov., Findings: Between Jan 31, 2019, and June 7, 2021, 676 patients were screened for inclusion in the SUNSHINE trial, of whom 541 (80%; 304 [56%] women and 237 [44%] men; mean age 36·1 years [SD 11·7]) were included in the analysis (181 [33%] in the secukinumab every 2 weeks group, 180 [33%] in the secukinumab every 4 weeks group, and 180 [33%] in the placebo group). Between the same recruitment dates, 687 patients were screened for inclusion in the SUNRISE trial, of whom 543 (79%; 306 [56%] women and 237 [44%] men; mean age 36·3 [11·4] years) were included in the analysis (180 [33%] in the secukinumab every 2 weeks group, 180 [33%] in the secukinumab every 4 weeks group, and 183 [34%] in the placebo group). In the SUNSHINE trial, significantly more patients in the secukinumab every 2 weeks group had a hidradenitis suppurativa clinical response (rounded average number of patients with response in 100 imputations, 81·5 [45%] of 181 patients) compared with the placebo group (60·7 [34%] of 180 patients; odds ratio 1·8 [95% CI 1·1-2·7]; p=0·0070). However, there was no significant difference between the number of patients in the secukinumab every 4 weeks group (75·2 [42%] of 180 patients) and the placebo group (1·5 [1·0-2·3]; p=0·042). Compared with the placebo group (57·1 [31%] of 183 patients), significantly more patients in the secukinumab every 2 weeks group (76·2 [42%] of 180 patients; 1·6 [1·1-2·6]; p=0·015) and the secukinumab every 4 weeks group (83·1 [46%] of 180 patients; 1·9 [1·2-3·0]; p=0·0022) had a hidradenitis suppurativa clinical response in the SUNRISE trial. Patient responses were sustained up to the end of the trials at week 52. The most common adverse event by preferred term up to week 16 was headache in both the SUNSHINE (17 [9%] patients in the secukinumab every 2 weeks group, 20 [11%] in the secukinumab every 4 weeks group, and 14 [8%] in the placebo group) and SUNRISE (21 [12%] patients in the secukinumab every 2 weeks group, 17 [9%] in the secukinumab every 4 weeks group, and 15 [8%] in the placebo group) trials. No study-related deaths were reported up to week 16. The safety profile of secukinumab in both trials was consistent with that previously reported, with no new or unexpected safety findings detected., Interpretation: When given every 2 weeks, secukinumab was clinically effective at rapidly improving signs and symptoms of hidradenitis suppurativa with a favourable safety profile and with sustained response up to 52 weeks of treatment., Funding: Novartis Pharma., Competing Interests: Declaration of interests ABK reports grants from AbbVie, Anapyts Bio, Aristea, Bristol Myers Squibb, ChemoCentryx, Eli Lilly, Incyte, Janssen, Moonlake, Novartis, Pfizer, UCB, and Sonoma Bio and fellowship funding from AbbVie and Janssen paid to her institution; royalties from BIDMC; consulting fees from AbbVie, Alumis, Bayer, Bristol Myers Squibb, Boehringer-Ingelheim, Eli Lilly, FIDE, Novartis, Moonlake, Janssen, Pfizer, Priovant, Sonoma Bio, Sanofi, Target RWE, UCB, and Ventyx; stock in Ventyx; serving on advisory boards for Target RWE; serving as an advisory council member to the National Institute of Health Director; and serves on the board of directors of Almirall. GBEJ reports grants from AbbVie, Boehringer-Ingelheim, CSL Behring, Regeneron, InflaRx, Novartis, LEO Foundation, and UCB, paid to their institution, and honoraria for advisory board meetings from Coloplast, Union Therapeutics, Toosonix, Boehringer-Ingelheim, Kymera, Sanofi, Viela Bio, ChemoCentryx, LEO Pharma, Afyx, Incyte, InflaRx, Janssen Cilag, Novartis, and UCB. AA reports consulting fees from AbbVie, Boehringer-Ingelheim, InflaRx, and UCB, paid to their institution, and consulting fees from Novartis, AbbVie, and Boehringer-Ingelheim. ZR reports consulting fees and honoraria from AbbVie, Amgen, Janssen-Cilag, Novartis, UCB, Sanofi; consulting fees from Celltrion; personal fees for attending meetings or for travel from AbbVie, Janssen-Cilag, Novartis, UCB, and Sanofi; and payment for expert testimony from AbbVie, Amgen, Celltrion, Janssen-Cilag, Novartis, and UCB. ABG reports research and educational grants from AnaptysBio, Janssen, Novartis, Ortho Dermatologics, Sun Pharma, BMS, and UCB Pharma, paid to their institution; consulting fees from Amgen, AnaptysBio, Avotres Therapeutics, Boehringer-Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi, Sun Pharma, UCB Pharma, and DiCE Therapeutics; honoraria as an advisory board member, or non-promotional speaker from Amgen, AnaptysBio, Avotres Therapeutics, Boehringer-Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi, Sun Pharma, and UCB Pharma; is a president of International Dermatology Outcome Measures; and holds stock options in XBiotech, for work on a rheumatoid arthritis project. FGB reports consulting fees from AbbVie, Novartis, and UCB; honoraria and support for attending meetings or travel from AbbVie, Janssen Cilag, Novartis, and UCB; and served on a Data Safety Monitoring Board or Advisory Board for AbbVie, Boehringer-Ingelheim, Janssen Cilag, Novartis, UCB, Incyte, and Moonlake. CP reports consulting fees from Almirall, AbbVie, Amgen, BMS, Boehringer-Ingelheim, Celgene, GSK, Janssen, LEO Pharma, Eli Lilly, Merck, Novartis, Pfizer, Sanofi, and UCB and served on a Data Safety Monitoring Board or Advisory Board for IQVIA. EJGB reports grants from Horizon 2020 ImmunoSep and RISKinCOVID, Horizon Health EPIC-CROWN-2, Sobi, bioMérieux, MSD, Abbott, Novartis, UCB, and AbbVie, paid to their institution, and consulting fees from Sobi, Pfizer, Abbott, ThermoFisher, and Menarini. APV reports consulting fees from Janssen-Cilag; payment or honoraria from AbbVie, Almirall, BMS, Janssen-Cilag, Leo Pharma, Eli Lilly, MSD, Novartis, and UCB; and support for attending meetings or travel from Janssen-Cilag and UCB. AS reports consulting fees from Regeneron, Novartis, and AbbVie, paid to their institution; payment or honoraria from AbbVie, Novartis, Regeneron, Sanofi; support for attending meetings or travel from AbbVie, Janssen-Cilag, Novartis, and Sanofi; and fees for participation on a Data Safety Monitoring Board or Advisory Board from AbbVie, Novartis, and Sanofi. FR reports grants from ALK-Abelló, Allergopharma, Blueprint Medicines, Mylan, Novartis, and ThermoFisher; served on a Data Safety Monitoring Board or Advisory Board for ALK-Abelló, Boehringer-Ingelheim, Blueprint Medicines, Leo Pharma, and UCB; and is an active member of the German Association of Allergy and Clinical Immunology. AR and his institution received grants from AbbVie, Alvotech, Amgen, AnaptysBio, Argenx, Biothera, Bristol Myers Squibb, Celgene, Celltrion, Dermira, Galderma, Inflarx, Janssen, Kiniksa, Kymab, Leo Pharma, Novartis, Pfizer, Trevi Therapeutics, and UCB; payment or honoraria from Chema Rzeszow, Eli Lilly, Leo Pharma, Novartis, Sandoz, and Takeda; and served on a Data Safety Monitoring Board or Advisory Board for AbbVie, Galderma, Sandoz, and Sanofi Aventis. IL reports payment or honoraria from Novartis and support for attending meetings or travel from Sanofi. TP reporfts grants from Almirall, Incyte, and Pfizer, paid to their institution, and consulting fees from AbbVie, Almirall, Bristol Myers Squibb, Eli Lilly, Galderma, Incyte, Janssen, LEO Pharma, Novartis, and UCB. AM reports consulting fees from AbbVie, Boehringer-Ingelheim, Jansen, Eli Lilly, Novartis, Novo Nordisk, Sandoz, and UCB; payment for expert testimony or honoraria from AbbVie, Boehringer-Ingelheim, Jansen, Eli Lilly, Novartis, Novo Nordisk, Sandoz, and UCB; and support for attending meetings or travel from AbbVie, Novartis, Jansen, and UCB. PM-B reports consulting fees from AbbVie, Almirall, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, and Sanofi; payment or honoraria from AbbVie, Almirall, Janssen, LEO Pharma, Eli Lilly, Novartis, Organon, Pfizer, Sanofi, and Viatris; support for attending meetings or travel from AbbVie, Almirall, Janssen, LEO Pharma, Eli Lilly, Novartis, and Sanofi; and served on a Data Safety Monitoring Board or Advisory Board for AbbVie, Janssen, LEO Pharma, Eli Lilly, Novartis, Pfizer, and Sanofi. GK reports consulting fees from Bayer; payment or honoraria from AbbVie, Abbott, Actelion Pharmaceuticals, Amgen, Basilea Pharmaceutica, Biogen IDEC, Boehringer-Ingelheim, Bristol Myers Squibb, Celgene, Hexal, Janssen-Cilag, LEO Pharma, Eli Lilly, MSD, Mylan, Novartis, Parexel, Pfizer, and UCB; support for attending meetings or travel from AbbVie, Abbott, Amgen, Basilea Pharmaceutica, Celgene, Janssen-Cilag, LEO Pharma, MSD, Novartis, Pfizer, Sanofi, and UCB; and served on a Data Safety Monitoring Board or Advisory Board for AbbVie, Abbott, Amgen, Basilea, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Celgene, Janssen-Cilag, LEO Pharma, Eli Lilly, Novartis, and UCB. P-AB reports consulting fees from Novartis, AbbVie, Pfizer, and UCB pharma; payment or honoraria from Novartis and AbbVie; support for attending meetings or travel from Novartis; and served on a Data Safety Monitoring Board or Advisory Board for Novartis. MBW, ALM, XW, LU, AP, DK, RM, CF, LC, MV, SR, and EM are employees of Novartis and hold company stock. RS is Director and Founder of Samson Medical, has participated in pharmaceutical advisory boards for Eli Lilly and Company, Pfizer, and Leo Pharmaceutical, has participated in speaker bureaus for AbbVie, Novartis, and Pfizer, and has acted as a principal investigator in clinical trials for AbbVie, Aerotech, Akesobio, Amgen, Arcutis, Arena, Ascend AstraZeneca, Bayer, Biotherapeutics Boehringer-Ingelheim, Bristol-Myer Squibb, Celgene, Coherus BioSciences, Connect, Demira, Eli Lilly, Galderma, GlaxoSmithKline, F Hoffman–La Roche, Janssen, MedImmune, Merck, Merck Sharpe & Dohme, Novartis, Oncobiologics, Pfizer, Principia, Regeneron, Roche, Reistone Biopharma, Samson Clinical, Sanofi-Genzyme, Sun Pharma UCB, Valeant, and Zai Labs. RS is President of the Australasian Hair and Wool Research Society, and Vice President of the International Society of Dermatology and The International Academy of Dermatology. LPR declares no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The paper presents research on the emission of pollutants from used car tires in the form of microparticles. Due to the large amount of waste generated in the form of used car tires, a method is being sought to utilize this material as secondary raw material. More and more frequently, this waste is used in civil engineering. To do this, it is necessary to determine the environmental impact of this waste. 2 g of microplastic samples with fractions of 3000-8000, 1000-3000, 1000, and 600 µm were incubated in water protected from light. The influence of pH (3, 7, and 10), incubation time (1, 3, 5, 7, and 14 d) and temperature (20, 60, and 90 °C) on the degree of emission of selected phthalic acid esters and other tire components was investigated. Additionally, the influence of the decomposition of the analyzed material on the emission of methane and carbon dioxide at the temperature of 20 °C during 30, 180, and 360 days was investigated. The analysis of the amount of released substances was carried out using a gas chromatograph coupled with a mass spectrometer. Greenhouse gas analysis was performed using a gas chromatograph with a Barrier Discharge Ionization Detector. The research carried out confirmed that, depending on the environmental conditions, tire particles leach out, among others, phthalates, benzenediamine, phenol, benzothiazole, and benzene. Influence of particle size, pH value, incubation time, and temperature on the degree of emission of selected plasticizers was investigated. An innovative aspect of the research was the use of artificial neural networks to identify the validity of using machine algorithms in environmental research. An additional negative aspect of the implementation of tire particles in the water-soil environment is the emission of carbon dioxide and methane that are greenhouse gases., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Multiple sclerosis (MS) is a chronic, neurodegenerative disease of central nervous system, characterized by inflammation, demyelination, and gliosis. It is commonly known the rapid and accurate diagnosis of MS determines treatment success. The standard diagnosis contains clinical symptoms observation, magnetic resonance imaging (MRI) of central nervous system (CNS), and analysis of cerebrospinal fluid (CSF). Nonetheless, since CSF sampling is considered invasive and not all individuals are eligible for MRI we have decided to propose other diagnostic tool such as spectroscopy. Unlike lumbar puncture, blood collection is a routine procedure regarded as low-invasive; therefore, we used Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy. This technique was combined with chemometrics and detailed spectral assay to analyse blood plasma and serum samples collected from MS patients and healthy individuals. The results revealed a clear identification pattern of MS, suggesting the conformation changes of amide III collagen-like proteins in plasma and the dominance of amide I β-sheet structures. Those changes in serum spectra seem to be useful for sample differentiation., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

There are limited data on amperometric biosensors (ABSs) based on deiminases that produce ammonium as a byproduct of enzymatic reaction. The most frequently proposed biosensors utilizing such a mode are based on potentiometric transducers, which contain at least two enzymes in the bioselective layer; this complicates the procedure and increases the cost of analysis. Thus, the construction of a one-enzyme ABS is a practical problem. In our manuscript ABSs for the direct measurement of creatinine (Crn) and l-arginine (Arg), based on the recombinant bacterial creatinine deiminase (CDI) and arginine deiminase (ADI), are described. To choose the best chemosensor on ammonium ions, a number of nanoparticles (NPs) were synthesized and characterized using cyclic voltammetry. Hybrid Cu/Zn(Hg)S-NPs, having a good selectivity and an extremely high sensitivities towards ammonium ions (5660 A M -1  m -2  at +170 mV and 1870 A M -1  m -2  at -300 mV, respectively), was selected for the development of deiminase-based ABSs. The novel biosensors exhibited very high sensitivities (2660 A M -1  m -2 to Crn for CDI-ABS; 1570 A M -1  m -2 to Arg for ADI-ABS), broad linear ranges, low limits of detection, satisfactory storage stabilities and good selectivities towards natural substrates. The constructed CDI-ABS and ADI-ABS were tested on real samples of biological fluids and juices for Crn and Arg assay, respectively. High correlations of the obtained results with the reference methods were demonstrated for the target analytes., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In this study, we verified the hypothesis that Raman signature of urinary extracellular vesicles (UEVs) can be used to stratify patients with diabetes at various stages of chronic kidney disease (CKD). Patients with type 2 diabetes diagnosed with different stages of CKD and healthy subjects were enrolled in the study. UEVs were isolated using low-vacuum filtration followed by ultracentrifugation. Correlation analysis, multiple linear regression and principal component analysis were used to find differences between spectral fingerprints of UEVs derived from both groups of patients. Electron microscopy and nanoparticle tracking analysis were applied to characterize the size and morphology of UEVs. We observed significant correlations between selected Raman bands measured for UEVs and clinical parameters. We found significant differences in the area under the specific bands originating mainly from proteins and lipids between the study groups. Based on the tryptophan and amide III bands, we were able to predict the estimated glomerular filtration rate (eGFR). Principal component analysis, partial least squares regression (PLSR) and correlation analysis of the UEV Raman spectra supported the results obtained from the direct analysis of Raman spectra. Our analysis revealed that PLSR and a regression model including tryptophan and amide III bands allows to estimate the value of eGFR., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

A procedure for adjusting the content of charge variants of monoclonal antibody by ion exchange chromatography has been developed. The band splitting phenomenon was utilized to split the protein load into two parts, i.e., the flowthrough and bound fractions, which were either enriched or depleted with some of variants. The phenomenon was triggered by thermodynamic effects resulting from oversaturation of the resin binding sites at high column loadings as well as from kinetic effects arising from limited rates of mass transport. Cation exchange chromatography (CEX) and anion exchange chromatography (AEX) separations were examined, with the reverse order of the variant elution: acidic, main, basic in CEX, and basic, main, acidic in AEX, and the corresponding reverse enrichment tendency in the collected fractions. The separations were performed by pH gradient, whose course was simplified to two stages: isocratic loading and washing at mild pH to load and partly elute the protein, followed by a rapid pH change towards non-binding conditions to desorb the remains of the protein load. To improve yield of the operation, possibility of recycling of waste fractions was considered. To predict the process performance, a dynamic model was developed, which accounted for both adsorption kinetics and thermodynamics., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

Objectives: To provide real-world data on the impact of autologous hematopoietic stem cell transplantation (AHSCT) on treatment costs of patients with multiple sclerosis (MS) in Poland., Methods: Medical data of 105 patients who underwent AHSCT in the years 2011 to 2016 were obtained from the National Health Fund (NHF) database. Treatment costs were calculated from the public payer's perspective per patient-year for the total available period as well as 12 months before and after AHSCT. The statistical analysis was performed using MATLAB 2016b., Results: Mean treatment-related costs covered by the NHF per patient-year before and after the transplantation were €4314.9 and €1188.8 , respectively. The average cost of disease-modifying drugs per patient was reduced from €2497.9/year before to €65.3/year after AHSCT., Conclusions: Although the initial cost of AHSCT is high, the costs involving AHSCT and post-AHSCT treatment could, according to our analysis, pay off in 3.9 years, when compared to the costs of disease-modifying drug therapy in aggressive MS. The study provides evidence that the AHSCT can lead to significant savings in treatment costs of aggressive MS from the public payer's perspective., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: Renal cell carcinoma (RCC) is a very aggressive and often fatal heterogeneous disease that is usually asymptomatic until late in the disease. There is an urgent need for RCC specific biomarkers that may be exploited clinically for diagnostic and prognostic purposes., Materials/methods: Serum and urine samples were collected from patients with diagnosed kidney cancer and assessed with gold nanoparticle enhanced target (AuNPET) surface assisted-laser desorption/ionization mass spectrometry (SALDI MS) based metabolomics and statistical analysis., Results: A database search allowed providing assignment of signals for the most promising features with a satisfactory value of the area under the curve and accuracy. Four potential biomarkers were found in urine and serum samples to distinguish clear cell renal cell carcinoma (ccRCC) from controls, 4 for the ccRCC with and without metastases, and 6 metabolites to distinguish low and high stages or grades., Conclusions: This pilot study suggests that serum and urine metabolomics based on AuNPET-LDI MS may be useful in distinguishing types, grades and stages of human RCC., Competing Interests: Declaration of competing interest The authors declare no competing and financial interest., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Marzeptacog alfa (activated) (MarzAA), a novel recombinant activated human factor VII (FVIIa) variant, was developed to provide increased procoagulant activity, subcutaneous (SC) administration, and longer duration of action in people with hemophilia., Objectives: To investigate if daily SC administration of MarzAA in subjects with inhibitors can provide effective prophylaxis., Methods: This multicenter, open-label phase 2 trial (NCT03407651) enrolled men with severe congenital hemophilia with an inhibitor. All subjects had a baseline annualized bleeding rate (ABR) of ≥12 events/year. Subjects received a single 18 μg/kg intravenous dose of MarzAA to measure 24-hour pharmacokinetics (PK) and pharmacodynamics (PD), single 30 μg/kg SC dose to measure 48-hour PK/PD, then daily SC 30 μg/kg MarzAA for 50 days. If spontaneous bleeding occurred, the dose was sequentially escalated to 60, 90, or 120 μg/kg, with 50 days at the final effective dose without spontaneous bleeding to proceed to a 30-day follow-up. The primary end point was reduction in ABR. Secondary end points were safety, tolerability, and antidrug antibody (ADA) formation., Results: In the 11 subjects, the mean ABR significantly reduced from 19.8 to 1.6, and the mean proportion of days with bleeding significantly reduced from 12.3% to 0.8%. Of a total of 517 SC doses, six injection site reactions in two subjects were reported. No ADAs were detected. One fatal unrelated serious adverse event occurred: intracerebral hemorrhage due to untreated hypertension., Conclusions: The data demonstrated that MarzAA was highly efficacious for prophylactic treatment in patients with inhibitors by significantly decreasing bleed frequency and duration of bleeding episodes., (© 2021 Catalyst Biosciences. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Multimodal polymer encapsulated CdSe/Fe 3 O 4 nanoplatforms with dual optical and magnetic properties have been fabricated. We demonstrate that CdSe/Fe 3 O 4 nanocapsules (NCs) upon excitation with UV radiation or NIR fs-laser excitation exhibit intense one- or two-photon emission at 535 nm, whereas the combination of an alternating magnetic field and 808 nm IR laser excitation results in heat generation. Since anticancer therapies require relatively high doses of Fe 3 O 4 nanoparticles (NPs) to induce biologically relevant temperature jumps, the therapeutic effects of 0.1 and 1 mg/mL Fe 3 O 4 NCs and CdSe/Fe 3 O 4 NCs were investigated using breast cancer cell lines, ER-positive MCF-7, and triple-negative MDA-MB-231 cells. Improved biocompatibility of CdSe/Fe 3 O 4 NCs compared to Fe 3 O 4 NCs was revealed at higher NCs concentration suggesting safe potential medical applications of CdSe/Fe 3 O 4 NCs. In contrast, 1 mg/mL Fe 3 O 4 NCs were found to be more cytotoxic to MDA-MB-231 than MCF-7 cells through iron-induced oxidative stress, lipid peroxidation, and concomitant ferroptotic cell death. We believe that Fe 3 O 4 NCs-mediated cellular response may be heterogeneous that reflects, at least in part, cancer cell genotype, molecular phenotype, and pathological classification., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

The ternary HAp/curdlan/nanomagnetite hybrids with ceramic and polymer phase incorporation of magnetite nanoparticles (MNPs) were fabricated to study their heating ability under action of the alternating magnetic field (AMF), 808 nm near infrared laser radiation (NIR) and their synergic stimulation. The energy conversion was evaluated in terms of the specific absorption rate (SAR) as a function of the MNPs concentration in composites and to estimate their potential in temperature-controlled regenerative processes and hyperthermia. Measurements were carried out on dry and Ringer's solution soaked composite materials in order to mimic in situ conditions. It was found that the MNPs release during prolonged experiment is limited and has no significant effect on energy conversion emphasizing stability of the hybrids. Incorporation of the MNPs in polymer phase of the hybrid can additionally limit particle leaking as well as plays a role as insulating layer for the heat dissipation lowering the risk of sample overheating. In general, it was shown that maximum temperature of hybrid can be achieved in a relatively short time of exposure to stimulating factors whereas its control can be done through optimization of experiment conditions. MNPs incorporation into the curdlan (polymer phase) lead to strengthening of the mechanical properties of the whole network., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The study of the experimental and calculated heat capacity, C p of fish collagen (silver carp) with contents of several additive components was presented. The experimental low-temperature heat capacity was measured in the temperature range of 1.85 to 302.8 K using a Quantum Design Physical Property Measurement System (PPMS) and the higher temperature C p from 223.15 K to 382.15 K by Differential Scanning Calorimetry (DSC) method. For an interpretation of the experimental, low-temperature data, the vibrational heat capacity of the pure silver carp collagen was calculated based on the contribution of a sum of the vibrational heat capacity of 4248 amino acids. The vibrational heat capacity for each amino acids was taken from Advanced Thermal Analysis System (ATHAS) Data Bank for individual poly (amino acid) residues based on their group and skeletal vibrational spectra. Comparing of the experimental heat capacity of the collagen with additive components and the calculated vibrational heat capacity of the pure silver carp collagen shows that the differences range from around 10% at 100 K to 14% at 300 K temperature. Such thermal analysis can provide information about the contribution to C p of unknown components or impurities in the investigated system., (Copyright © 2020 Elsevier B.V. All rights reserved.)

There is a clear trend in the world to increase the use of sustainable drainage systems. In Poland, it is not as much noticeable, and as a consequence, the conventional stormwater system remains the most common method of stormwater management. As part of the research, an assessment of the issues affecting the implementation of sustainable stormwater management systems in an engineering practices was performed. For that purpose the PESTLE analysis was applied. Its results indicate that legal factors are the key for the development of sustainable drainage systems in Poland. The scale of public support and availability of funding is also not without importance. The possibilities of the implementation growth of sustainable drainage systems should be sought in changes in legal regulations regarding stormwater management, while ensuring at the same time an appropriate level of financing for sustainable solutions. In the second stage of the research, stormwater management models used in Poland were identified. The strengths and weaknesses of these models were presented. There were also discussed the potential opportunities and threats associated with their implementation. The balances of positive and negative sides that were created through a SWOT analysis could be treated as the basis for the detailed analyses of the legitimate application of individual systems in specific areas. It is expected that the results of the research will allow formulating clear principles of an innovation policy in the field of stormwater management and appointing objective and transparent criteria for financing individual types of drainage investments., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Nitroxides and nitroxide-containing nanoparticles (RNP) are excellent antioxidants. However, they have relatively high reduction potentials, which make them behave like oxidants or show little activity in some antioxidant assays. We found that stable nitroxyl radicals (TEMPO and 4-amino-TEMPO) has low reactivity in the test of scavenging of 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radical (ABTS • ). As a result, supplementation of blood plasma with nitroxides may decrease its total antioxidant capacity assayed with ABTS • . Nitroxides oxidize Fe 2+ and in this way interfere with the ferric-Xylenol Orange assay of peroxides. Nitroxides as well as RNP directly oxidize glutathione and fluorogenic probes used for estimation of reactive oxygen species (ROS) (dihydro-2'7'-dichlorofluorescein diacetate, dihydroethidine and dihydrorhodamine 123) and thus produce artefacts in assays of glutathione and ROS in cell-free and cellular systems. These results point to the necessity of careful interpretation of antioxidant assays concerning nitroxides and RNP or performed in their presence., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In the present study, we compared the anticancer potential of quercetin (3,3',4',5,7-pentahydroxyflavone, I) and its sulfonic derivatives sodium/potassium quercetin-5'-sulfonates (described as II and III) against several human carcinoma cell lines. Quercetin (I) was used as a starting compound for synthesis of II and III. In this work, a modified and more efficient method of synthesizing derivatives II and III has been described. The molecular structures of the compounds were characterized in a solution and in the solid state using 1 H NMR, 13 C NMR, 2D NMR, and XPS spectroscopy, respectively. The stoichiometry of these complexes was determined by elemental analysis as well as thermogravimetric and X-ray fluorescence methods. The spectral data allowed complete characterization of the investigated compounds in the solution and in the solid state and unambiguous determination of the place of substitution of the sulfonic group in the phenyl ring in the C-5' position. Our in vitro studies revealed that II and III prominently reduced the viability of the HT-29 colon cancer cell line. Additionally, we observed that sulfonic derivatives decreased proliferation of colon (HT-29, LS180), lung (A549), and breast (T47D) cancer cell lines. Moreover, we detected a lower cytotoxic effect of II and III on several normal cell lines (colon epithelial CCD 841 CoTr, mouse subcutaneous connective tissue L-929, and human skin fibroblasts HSF cell lines) than that exerted by pure quercetin. The anticancer properties were especially evident in the HT-29 colon cancer cell line, where cell cycle inhibition in the G 2 -M phase and prominent apoptosis induced by II and III were observed. In conclusion, the sodium/potassium quercetin-5'-sulfonates prepared from quercetin showed promising anti-proliferative and pro-apoptotic activity against colon cancer cells. Therefore, we support the opinion that sodium/potassium quercetin-5'-sulfonates should be considered as promising organometallic compounds for possible clinical applications., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In this paper the properties of thermosensitive chitosan hydrogels, formulated with chitosan chloride with β-glycerophosphate disodium salt hydrate and chitosan chloride with β-glycerophosphate disodium salt hydrate enriched with calcium glycerophosphate, are presented. The study focused on the determination of the hydrogel structure after conditioning in water. The structure of the gels was investigated by Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). The crystallinity of the gel structure was determined by X-ray diffraction analysis (XRD) and the thermal effects were determined based on DSC thermograms., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Silica-chitosan hybrid beads were synthesized via three different methods to investigate the selective recovery of REE from AMD. The influence of amino/non-amino silanes, high molecular weight/high viscous chitosan and N-/O- based ligands were studied and their effects on REE removal efficiencies were analyzed. The adsorption efficiencies of three various groups of modified beads were inspected with respect to feed pH, in a single and a multi-component system, and their affinities towards the light and heavy rare earth elements (LREE/ HREEs) were interpreted to understand the intra-series REE separation behavior. The focus of the study was mainly directed towards utilizing these fabricated beads for the recovery of valuable REEs from the real AMD obtained at three different sampling depths which was found rich in iron, sulfur and aluminum. Moreover, the selectivity of the beads towards REEs improved with silanized and ligand immobilized gels and their impacts on REE recovery in the presence of competing ions were successfully presented in this paper. Also, the synthesized beads showed rapid REE adsorption and recovery within a process time of 5 min. Group II adsorbents, synthesized by forming silica-chitosan hybrid beads followed by PAN/acac modifications, showed superiority over the other groups of adsorbents., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Lipids in extracellular matrices (ECM) contribute to barrier function and stability of epithelial tissues such as the pulmonary alveoli and the skin. In insects, skin waterproofness depends on the outermost layer of the extracellular cuticle termed envelope that contains cuticulin, an unidentified water-repellent complex molecule composed of proteins, lipids and catecholamines. Based on live-imaging analyses of fruit fly larvae, we find that initially envelope units are assembled within putative vesicles harbouring the ABC transporter Snu and the extracellular protein Snsl. In a second step, the content of these vesicles is distributed to cuticular lipid-transporting nanotubes named pore canals and to the cuticle surface in dependence of Snu function. Consistently, the surface of snu and snsl mutant larvae is depleted from lipids and cuticulin. By consequence, these animals suffer uncontrolled water loss and penetration of xenobiotics. Our data allude to a two-step model of envelope i.e. barrier formation. The proposed mechanism in principle parallels the events occurring during differentiation of the lipid-based ECM by keratinocytes in the vertebrate skin suggesting establishment of analogous mechanisms of skin barrier formation in vertebrates and invertebrates., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

An approach to conducting SFC separations under pseudo-adiabatic condition utilizing a dual-zone column heater is described. The heater allows for efficient separations at low pressures above the critical temperature by imposing a temperature profile along the column wall that closely matches that for isenthalpic expansion of the fluid inside the column. As a result, the efficiency loss associated with the formation of radial temperature gradients in this difficult region can be largely avoided in packed analytical scale columns. For elution of n-octadecylbenzene at 60 °C with 5% methanol modifier and a flow rate of 3 mL/min, a 250 × 4.6-mm column packed with 5-micron Kinetex C18 particles began to lose efficiency (8% decrease in the number of theoretical plates) at outlet pressures below 142 bar in a traditional forced air oven. The corresponding outlet pressure for onset of excess efficiency loss was decreased to 121 bar when the column was operated in a commercial HPLC column heater, and to 104 bar in the new dual-zone heater operated in adiabatic mode, with corresponding increases in the retention factor for n-octadecylbenzene from 2.9 to 6.8 and 14, respectively. This approach allows for increased retention and efficient separations of otherwise weakly retained analytes. Applications are described for rapid SFC separation of an alkylbenzene mixture using a pressure ramp, and isobaric separation of a cannabinoid mixture., (Copyright © 2018 Elsevier B.V. All rights reserved.)

When an SFC column is operated in a traditional oven with forced air at low pressures near the critical temperature, severe efficiency losses can occur. The mobile phase cools as it expands along the column, forming axial and radial temperature gradients. In this study we present a simple model based on a virtual fluid to predict the conditions which lead to the onset of efficiency loss. The model shows that the Joule-Thomson coefficient is an important factor leading to efficiency loss in packed columns under forced air conditions. The model was tested experimentally for elution of n-alkylbenzenes on 250×4.6-mm ID columns packed with 5-μm Luna-C18 (fully porous) and Kinetex-C18 (superficially porous) particles at optimum flow rates in a forced air oven at 20-80°C and outlet pressures from 90 to 250bar, with CO 2 mobile phase containing 5, 10 and 20% methanol (v/v). For simplicity, we used a formal J-T coefficient corresponding to the inlet temperature and the outlet pressure to characterize the chromatographic conditions. For 5% methanol, there was no significant loss of efficiency for elution of n-octadecylbenzene as long as the formal J-T coefficient was less than 0.11K/bar for Luna or 0.15K/bar for Kinetex, with minimum reduced plate heights equal to 1.82 and 1.55, respectively, at an average apparent retention factor of approximately 4.0 for both columns. The Kinetex column provided superior efficiency in general, and at 10-20bar lower outlet pressures relative to the Luna column due to the higher thermal conductivity of the packing. Results for 10 and 20% methanol showed similar trends but were less predictable., (Copyright © 2016 Elsevier B.V. All rights reserved.)

An 8-zone simulated moving bed chromatography with internal recycle (8ZSMB-IR) has been designed for center-cut separation, that is, for isolating an intermediately adsorbed component out of a multicomponent mixture. The system consists of two integrated subunits and operates in a fully continuous manner. In the first subunit the feed mixture is split into two fractions containing either a single component or a binary mixture. The binary mixture is recycled through the internal raffinate or extract port into the second subunit, where the target product is isolated. Additionally, the solvent is also recycled internally. For a case study, the separation of a ternary mixture of cycloketones as a model system under weakly non-linear isotherm conditions has been investigated. A few novel configurations of the 8ZSMB-IR unit including the arrangement of the internal recycle of extract, raffinate and solvent streams between two subunits have been examined with respect to various performance indicators for the process realization. The unit performed best with the developed configuration when the internal raffinate stream was recycled and the solvent recycling loop was closed between the last and the first zone of the first subunit. That configuration has further been analyzed experimentally and numerically. On the basis of the results a strategy for determining reliable operating conditions for the 8ZSMB-IR process has been developed. The procedure exploited a model of the process dynamics, which was implemented to refine the isotherm coefficients and to quantify the mixing effect of the liquid stream inside the recycling loops. The upgraded model with the adjusted parameters has been validated based on experimental data and successfully applied for optimizing the operating conditions of the separation., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In the recent years, nanotechnology is the most developing branch due to a wide variety of potential applications in biomedical, biotechnological and agriculture fields. The binding nanoparticles with various biological molecules makes them attractive candidates for using in sensor technologies. The particularly actual is obtaining the bionanomembranes based on biocatalytic elements with improved sensing characteristics. The aim of this investigation is to study the properties of microbial L-lactate-selective sensor based on using the recombinant Hansenula polymorpha yeast cells overproducing flavocytochrome b2 (FC b2), as well as additionally enriched by the enzyme bound with gold nanoparticles (FC b2-nAu). Although, the high permeability of the living cells to nanoparticles is being intensively studied (mostly for delivery of drugs), the idea of using both recombinant technology and nanotechnology to increase the amount of the target enzyme in the biosensing layer is really novel. The FC b2-nAu-enriched living and permeabilized yeast cells were used for construction of a bioselective membrane of microbial L-lactate-selective amperometric biosensor. Phenazine methosulphate was served as a free defusing electron transfer mediator which provides effective electron transfer from the reduced enzyme to the electrode surface. It was shown that the output to L-lactate of FC b2-nAu-enriched permeabilized yeast cells is 2.5-fold higher when compared to the control cells. The obtained results confirm that additional enrichment of the recombinant yeast cell by the enzyme bound with nanoparticles improves the analytical parameters of microbial sensor., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The impact of the solubility limits on the performance of gradient protein chromatography has been studied. As a case study elution of model protein, i.e., lysozyme, on hydrophobic interaction media has been selected. A dependence of the protein solubility and crystallization kinetics on the content of cosmotropic salt in the mobile phase has been determined. Moreover, adsorption properties of the protein versus the mobile phase composition have been quantified. A model of chromatographic column dynamics has been developed which incorporated the mass transport kinetics accompanying both adsorption and crystallization processes. The model was used to study the influence of operating parameters such as flowrate and concentration loading on the solubility pattern inside the column and the separation performance. The analysis performed indicated existence of supersaturation regions for which, due to slow kinetics of crystallization, chromatographic process could be performed under conditions of strong concentration overloading while avoiding undesirable effects of flow blockage in chromatographic systems., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The study of modified synthetic procedure of water soluble morin-5'-sulfonic acid sodium salt (NaMSA) involving less aggressive chemicals and carried out at mild conditions was described. The NaMSA salt is a convenient source of anionic morin-5'-sulfonic ligand (MSA) in ion exchange reactions. The coordination ability of MSA ligand towards the zinc cations was investigated in aqueous solution and in solid state. Novel zinc complexes of morin-5'-sulfonate were obtained by a reaction of Zn(NO3)2 with morin-5'-sulfonate in water. Resulting compounds were characterized by single-crystal X-ray diffraction analysis, as well as spectral and thermal methods. The coordination interaction, hydrogen bond and π-π stacking lead to the formation of a 1D chain or 3D coordination polymers. The antioxidant activity of the Zn(II)-MSA complexes was evaluated by means of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging method. In this work, we have shown that the studied compounds are more effective free radical scavengers than the natural flavonoids like plain morin., (Copyright © 2014. Published by Elsevier Inc.)

We propose to use constant enthalpy or isenthalpic diagrams as a tool to estimate the extent of the temperature variations caused by the mobile phase pressure drop along a chromatographic column, e.g. of its cooling in supercritical fluid and its heating in ultra-performance liquid chromatography. Temperature strongly affects chromatographic phenomena. Any of its variations inside the column, whether intended or not, can lead to significant changes in separation performance. Although instruments use column ovens in order to keep constant the column temperature, operating conditions leading to a high pressure drop may cause significant variations of the column temperature, both in the axial and the radial directions, from the set value. Different ways of measuring these temperature variations are available but they are too inconvenient to be employed in many practical situations. In contrast, the thermodynamic plot-based method that we describe here can easily be used with only a ruler and a pencil. They should be helpful in developing methods or in analyzing results in analytical laboratories. Although the most effective application area for this approach should be SFC (supercritical fluid chromatography), it can be applied to any chromatographic conditions in which temperature variations take place along the column due to the pressure drop, e.g. in ultra-high pressure liquid chromatography (UHPLC). The method proposed here is applicable to isocractic conditions only., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objectives: To critically evaluate the effectiveness of yoga as a treatment of hypertension., Methods: Seventeen databases were searched from their inceptions to January 2014. Randomized clinical trials (RCTs) were included, if they evaluated yoga against any type of control in patients with any form of arterial hypertension. Risk of bias was estimated using the Cochrane criteria. Three independent reviewers performed the selection of studies, data extraction, and quality assessments., Results: Seventeen trials met the inclusion criteria. Only two RCTs were of acceptable methodological quality. Eleven RCTs suggested that yoga leads to a significantly greater reduction in systolic blood pressure (SBP) compared to various forms of pharmacotherapy, breath awareness or reading, health education, no treatment (NT), or usual care (UC). Eight RCTs suggested that yoga leads to a significantly greater reduction in diastolic blood pressure (DBP) or night-time DBP compared to pharmacotherapy, NT, or UC. Five RCTs indicated that yoga had no effect on SBP compared to dietary modification (DIM), enhanced UC, passive relaxation (PR), or physical exercises (PE). Eight RCTs indicated that yoga had no effect on DBP compared to DIM, enhanced UC, pharmacotherapy, NT, PE, PR, or breath awareness or reading. One RCT did not report between-group comparisons., Conclusion: The evidence for the effectiveness of yoga as a treatment of hypertension is encouraging but inconclusive. Further, more rigorous trials seem warranted., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The pressure, temperature and density drops along SFC columns eluted with a CO2/methanol mobile phase were measured and compared with theoretical values. For columns packed with 3- and 5-μm particles the pressure and temperature drops were measured using a mobile phase of 95% CO2 and 5% methanol at a flow rate of 5mL/min, at temperatures from 20 to 100°C, and outlet pressures from 80 to 300bar. The density drop was calculated based on the temperature and pressure at the column inlet and outlet. The columns were suspended in a circulating air bath, either bare or covered with foam insulation. The experimental measurements were compared to theoretical results obtained by numerical simulation. For the convective air condition at outlet pressures above 100bar the average difference between the experimental and calculated temperature drops and pressure drops were 0.1°C and 0.7% for the bare 3-μm column, respectively, and were 0.6°C and 4.1% for the insulated column. The observed temperature drops for the insulated columns are consistent with those predicted by the Joule-Thomson coefficients for isenthalpic expansion. The dependence of the temperature and the pressure drops on the Joule-Thomson coefficient and kinematic viscosity are described for carbon dioxide mobile phases containing up to 20% methanol., (Copyright © 2013 Elsevier B.V. All rights reserved.)