Polymer stain resistance: Prediction versus experiment

The coloration of different polymer films (from commodity and packaging films to performance films) by contact with various food coloring substances was evaluated. For this purpose, both solubility parameters as a prediction tool, and immersion experiments for time range between 24 and 1000 h were established. The two predicting tools are the Hoy and Hoftyzer‐Van Krevelen (HVK) methods. For PE and PP, HVK's method is preferred for predicting coloration. Neither of the HVK's and Hoy's methods was able to establish a coloration prediction for PET while both methods could predict the staining of PEEK. The coloration of partially and fully fluorinated polymers is well predicted by the Hoy's method. The behavior of PP/PA and PP/PA/PP multilayer films was also studied. Crystallinity degree of polymers, temperature and concentration of coloring molecules are also important parameters, which are not taken into account in solubility theories. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Chitosan effects on glass matrices evaluated by biomaterial. MAS-NMR and biological investigations

Bioactive glass 46S6 and biodegradable therapeutic polymer (Chitosan: CH) have been elaborated to form 46S6-CH composite by freeze-drying process. The kinetics of chemical reactivity and bioactivity at the surface were investigated by using physicochemical techniques, particularly solid-state MAS-NMR. Immortalized cell line used to construct multicellular spheroids was employed as three-dimensional (3D) cell cultures for in vitro studies. Obtained results showed a novel structure of the composite; the chemical treatment (ultrasound, magnetic stirring, freeze drying process and lyophilization) led the bioactive glass particles to be loaded in the chitosan-based materials. ²⁹Si and ³¹P MAS-NMR results showed the emergence of two new species, Q _Si ³ (OH) and Q _Si ⁴ , which are characteristic of the vitreous network dissolution in simulated body fluid (SBF). MAS-NMR also confirmed the formation of amorphous calcium phosphate (ACP) at the surface of the initial 46S6-CH. Three-dimensional (3D) cell cultures highlighted the effect of chitosan, where the cell viability reached up to 78% in 46S6-CH composite and up to 67% in 46S6. The association of (CH) and bioactive glass (BG) matrix promotes a highly significant bioactivity, demonstrating surface bone formation and satisfactory behavior in biological environment.     

PCA3 and PCA3-Based Nomograms Improve Diagnostic Accuracy in Patients Undergoing First Prostate Biopsy

While now recognized as an aid to predict repeat prostate biopsy outcome, the urinary PCA3 (prostate cancer gene 3) test has also been recently advocated to predict initial biopsy results. The objective is to evaluate the performance of the PCA3 test in predicting results of initial prostate biopsies and to determine whether its incorporation into specific nomograms reinforces its diagnostic value. A prospective study included 601 consecutive patients addressed for initial prostate biopsy. The PCA3 test was performed before ≥12-core initial prostate biopsy, along with standard risk factor assessment. Diagnostic performance of the PCA3 test was evaluated. The three available nomograms (Hansen’s and Chun’s nomograms, as well as the updated Prostate Cancer Prevention Trial risk calculator; PCPT) were applied to the cohort, and their predictive accuracies were assessed in terms of biopsy outcome: the presence of any prostate cancer (PCa) and high-grade prostate cancer (HGPCa). The PCA3 score provided significant predictive accuracy. While the PCPT risk calculator appeared less accurate; both Chun’s and Hansen’s nomograms provided good calibration and high net benefit on decision curve analyses. When applying nomogram-derived PCa probability thresholds ≤30%, ≤6% of HGPCa would have been missed, while avoiding up to 48% of unnecessary biopsies. The urinary PCA3 test and PCA3-incorporating nomograms can be considered as reliable tools to aid in the initial biopsy decision.     

Properties of phyllosilicate-based porous ceramics shaped by conventional tape casting and freeze tape casting

Silicate ceramics were shaped using tape casting (TC) and freeze tape casting (FTC) processes from three clays labeled HCR, KORS, and KCR. These clays exhibited mass content of 77% halloysite–10 Å, 29% kaolinite, and 98% kaolinite minerals, respectively. After casting the slurries, the dried tapes were sintered at 1200°C. The microstructure changes were characterized before and after sintering using scanning electron microscopy. The apparent porosity of TC samples was lower (36–47 vol.%) compared to values obtained with FTC samples (67–79 vol.%). The latter samples exhibited a highly textured porosity, with micron-sized pores aligned perpendicular to the tape surfaces. Upon sintering, the porosity of TC samples tended to decrease conversely to the case of FTC samples. Such behavior seemed related to the simultaneous effect of organic additives and ice templating. Consequently, the FTC samples showed a relatively low mechanical strength of 3–7 MPa and thermal conductivity of .14– .22 W m⁻¹ K⁻¹. After sintering, the mullite crystallization contributed to strengthen the bulk materials, helping to compensate for the detrimental effect of porosity on the stress to rupture and on thermal conductivity values.     

Mass Spectrometric Assays Reveal Discrepancies in Inhibition Profiles for the SARS-CoV-2 Papain-Like Protease

The two SARS-CoV-2 proteases, i. e. the main protease (M^pro) and the papain-like protease (PL^pro), which hydrolyze the viral polypeptide chain giving functional non-structural proteins, are essential for viral replication and are medicinal chemistry targets. We report a high-throughput mass spectrometry (MS)-based assay which directly monitors PL^pro catalysis in vitro. The assay was applied to investigate the effect of reported small-molecule PL^pro inhibitors and selected M^pro inhibitors on PL^pro catalysis. The results reveal that some, but not all, PL^pro inhibitor potencies differ substantially from those obtained using fluorescence-based assays. Some substrate-competing M^pro inhibitors, notably PF-07321332 (nirmatrelvir) which is in clinical development, do not inhibit PL^pro. Less selective M^pro inhibitors, e. g. auranofin, inhibit PL^pro, highlighting the potential for dual PL^pro/M^pro inhibition. MS-based PL^pro assays, which are orthogonal to widely employed fluorescence-based assays, are of utility in validating inhibitor potencies, especially for inhibitors operating by non-covalent mechanisms.     

The Efficacy of Fibrinogen Concentrates in Relation to Cryoprecipitate in Restoring Clot Integrity and Stability against Lysis

Loss of fibrinogen is a feature of trauma-induced coagulopathy (TIC), and restoring this clotting factor is protective against hemorrhages. We compared the efficacy of cryoprecipitate, and of the fibrinogen concentrates RiaSTAP^® and FibCLOT^® in restoring the clot integrity in models of TIC. Cryoprecipitate and FibCLOT^® produced clots with higher maximal absorbance and enhanced resistance to lysis relative to RiaSTAP^®. The fibrin structure of clots, comprising cryoprecipitate and FibCLOT^®, mirrored those of normal plasma, whereas those with RiaSTAP^® showed stunted fibers and reduced porosity. The hemodilution of whole blood reduced the maximum clot firmness (MCF) as assessed by thromboelastography. MCF could be restored with the inclusion of 1 mg/mL of fibrinogen, but only FibCLOT^® was effective at stabilizing against lysis. The overall clot strength, measured using the Quantra^® hemostasis analyzer, was restored with both fibrinogen concentrates but not cryoprecipitate. α₂antiplasmin and plasminogen activator inhibitor-1 (PAI-1) were constituents of cryoprecipitate but were negligible in RiaSTAP^® and FibCLOT^®. Interestingly, cryoprecipitate and FibCLOT^® contained significantly higher factor XIII (FXIII) levels, approximately three-fold higher than RiaSTAP^®. Our data show that 1 mg/mL fibrinogen, a clinically achievable concentration, can restore adequate clot integrity. However, FibCLOT^®, which contained more FXIII, was superior in normalizing the clot structure and in stabilizing hemodiluted clots against mechanical and fibrinolytic degradation.     

Circular RNAs in Pregnancy and the Placenta

The emerging field of circular RNAs (circRNAs) has identified their novel roles in the development and function of many cancers and inspired the interest of many researchers. circRNAs are also found throughout the healthy body, as well as in other pathological states, but while research into the function and abundance of circRNAs has progressed, our overall understanding of these molecules remains primitive. Importantly, recent studies are elucidating new roles for circRNAs in pregnancy, particularly in the placenta. Given that many of the genes responsible for circRNA production in cancer are also highly expressed in the placenta, it is likely that the same genes act in the production of circRNAs in the placenta. Furthermore, placental development can be referred to as ‘controlled cancer’, as it shares many key signalling pathways and hallmarks with tumour growth and metastasis. Hence, the roles of circRNAs in this field are important to study with respect to pregnancy success but also may provide novel insights for cancer progression. This review illuminates the known roles of circRNAs in pregnancy and the placenta, as well as demonstrating differential placental expressions of circRNAs between complicated and uncomplicated pregnancies.     

A mass spectrometric and molecular modelling study of cisplatin binding to transferrin

A combination of mass spectrometry, UV/Vis spectroscopy and molecular modelling techniques have been used to characterise the interaction of cisplatin with human serum transferrin (Tf). Mass spectrometry indicates that cisplatin binds to the hydroxy functional group of threonine 457, which is located in the iron(III)-binding site on the C-terminal lobe of the protein. UV/Vis spectroscopy confirms the stoichiometry of binding and shows that cisplatin and iron(III) binding are competitive. The binding of cisplatin has been modelled by using molecular dynamic simulations and the results suggest that cisplatin can occupy part of both the iron(III)- and carbonate-binding sites in the C-terminal lobe of the protein. Combined, the studies suggest that cisplatin binding sterically restricts iron(III) binding to the C-terminal lobe binding site, whereas the N-terminal lobe binding site appears to be unaffected by the cisplatin interaction, possibly allowing the iron(III)-induced conformational change necessary for binding to a Tf receptor.