Biohybrid Electrospun Membrane for the Filtration of Ketoprofen Drug from Water

A current challenge in materials science and biotechnology is to express a specific and controlled functionality on the large interfacial area of a nanostructured material to create smart biohybrid systems for targeted applications. Here, we report on a biohybrid system featuring poly(vinyl alcohol) as the supporting synthetic polymer and bovine serum albumin as the biofunctional element. The optimal processing conditions to produce these self-standing composite membranes are determined, and the composition and distribution of the bioactive agent within the polymeric matrices are analyzed. A post-processing cross-linking using glutaraldehyde enables this functional membrane to be used as a chemical filter in aqueous environments. By demonstrating that our mats can remove large amounts of ketoprofen from water, we show that the combination of a BSA-induced biofunctionality with a nanostructured fibrous material allows for the development of an efficient biohybrid filtering device for the large and widely used family of nonsteroidal anti-inflammatory drugs (NSAIDs). The crystal structure of the complex between BSA and ketoprofen is determined for the first time and confirms the interaction between the two species

Molecular dynamics simulations provide insights into the substrate specificity of FAOX family members

Enzymatic assays based on Fructosyl Amino Acid Oxidases (FAOX) represent a potential, rapid and economical strategy to measure glycated hemoglobin (HbA1c), which is in turn a reliable method to monitor the insurgence and the development of diabetes mellitus. However, the engineering of naturally occurring FAOX to specifically recognize fructosyl-valine (the glycated N-terminal residue of HbA1c) has been hindered by the paucity of information on the tridimensional structures and catalytic residues of the different FAOX that exist in nature, and in general on the molecular mechanisms that regulate specificity in this class of enzymes. In this study, we use molecular dynamics simulations and advanced modeling techniques to investigate five different relevant wild-type FAOX (Amadoriase I, Amadoriase II, PnFPOX, FPOX-E and N1-1-FAOD) in order to elucidate the molecular mechanisms that drive their specificity towards polar and nonpolar substrates. Specifically, we compare these five different FAOX in terms of overall folding, ligand entry tunnels, ligand binding residues and ligand binding energies. Our work will contribute to future enzyme structure modifications aimed at the rational design of novel biosensors for the monitoring of blood glucose levels

The interplay of soft-hard substituents in photochromic diarylethenes

A series of diarylethenes with substituents of different size and chemical nature was synthesised showing that beside some intermolecular interactions involving the central diarylethene core, lateral groups clearly play a key role in the crystal packing arrangements. These structural features were further analyzed in relation to the thermal data obtained by differential scanning calorimetry (DSC) and monitored using FT-IR spectroscopy, thus providing a rationalization of the observed thermal transitions processes. The role of van der Waals interactions is crucial in driving crystal packing formation towards loosely packed arrangements characterized by large hydrophobic contact areas. Interestingly, some functional substituents favour an amorphous state after thermal treatment, a peculiar feature that can be exploited to design uniform photochromic layers

Tailoring FPOX enzymes for enhanced stability and expanded substrate recognition

Abstract Fructosyl peptide oxidases (FPOX) are deglycating enzymes that find application as key enzymatic components in diabetes monitoring devices. Indeed, their use with blood samples can provide a measurement of the concentration of glycated hemoglobin and glycated albumin, two well-known diabetes markers. However, the FPOX currently employed in enzymatic assays cannot directly detect whole glycated proteins, making it necessary to perform a preliminary proteolytic treatment of the target protein to generate small glycated peptides that can act as viable substrates for the enzyme. This is a costly and time consuming step. In this work, we used an in silico protein engineering approach to enhance the overall thermal stability of the enzyme and to improve its catalytic activity toward large substrates. The final design shows a marked improvement in thermal stability relative to the wild type enzyme, a distinct widening of its access tunnel and significant enzymatic activity towards a range of glycated substrates

Hierarchical TiN-Supported TsFDH Nanobiocatalyst for CO2 Reduction to Formate

AbstractThe electrochemical reduction of CO2 to value‐added products like formate represents a promising technology for the valorization of carbon dioxide. We propose a proof‐of‐concept bioelectrochemical system (BES) for the reduction of CO2 to formate. For the first time, our device employs a nanostructured titanium nitride (TiN) support for the immobilization of a formate dehydrogenase (FDH) enzyme. The hierarchical TiN nanostructured support exhibits high surface area and wide pore size distribution, achieving high catalytic loading, and is characterized by higher conductivity than other oxide‐based supports employed for FDHs immobilization. We select the oxygen‐tolerant FDH from Thiobacillus sp. KNK65MA (TsFDH) as enzymatic catalyst, which selectively reduces CO2 to formate. We identify an optimal TiN morphology for the enzyme immobilisation through enzymatic assay, reaching a catalyst loading of 59 μg cm−2 of specifically‐adsorbed TsFDH and achieving a complete saturation of the anchoring sites available on the surface. We evaluate the electrochemical CO2 reduction performance of the TiN/TsFDH system, achieving a remarkable HCOO− Faradaic efficiency up to 76 %, a maximum formate yield of 44.1 μmol mg−1FDH h−1 and high stability. Our results show the technological feasibility of BES devices employing novel, nanostructured TiN‐based supports, representing an important step in the optimization of these devices

Population pharmacokinetics and probability of target attainment of meropenem in critically ill patients

Purpose: Patients admitted to intensive care unit (ICU) with Klebsiella pneumoniae infections are characterized by high mortality. The aims of the present study were to investigate the population pharmacokinetics parameters and to assess the probability of target attainment of meropenem in critically ill patients to provide information for more effective regimens. Methods: Twenty-seven consecutive patients were included in the study. Meropenem was administered as 3-h intravenous (i.v.) infusions at doses of 1\u20132 g every 8 or 12 h. Meropenem plasma concentrations were measured by a high-performance liquid chromatography (HPLC) method, and a population pharmacokinetics analysis was performed using NONMEM software. Meropenem plasma disposition was simulated for extended (3 h; 5 h) or continuous i.v. infusions, and the following parameters were calculated: time during which free drug concentrations were above minimum inhibitory concentration (MIC) (fT > MIC), free minimum plasma concentrations above 4 7 MIC (fCmin > 4 7 MIC), probability of target attainment (PTA), and cumulative fraction of response (CFR). Results: Gender and severity of sepsis affected meropenem clearance, whose typical population values ranged from 6.22 up to 12.04 L/h (mean \ub1 standard deviation (SD) value, 9.38 \ub1 4.47 L/h). Mean Cmin value was 7.90 \ub1 7.91 mg/L, suggesting a high interindividual variability. The simulation confirmed that 88 and 97.5 % of patients achieved effective Cmin > 4 7 MIC values after 3- and 5-h i.v. infusions of meropenem 2 g  7 3/day, respectively. On the contrary, the same total daily doses reached the target Cmin > 4 7 MIC values in 100 % of patients when administered as continuous i.v. infusions. Conclusions: Several factors may influence meropenem pharmacokinetics in ICU patients. Continuous i.v. infusions of meropenem seem to be more effective than standard regimens to achieve optimal therapeutic targets

Growing old with antiretroviral therapy or elderly people in antiretroviral therapy: two different profiles of comorbidity?

Background In persons living with HIV (PLWH), the burden of non-communicable chronic diseases increased over time, because of aging associated with chronic inflammation, systemic immune activation, and long-term exposure to the combination antiretroviral therapy (ART). Methods To explore the association of chronological age, age at first ART, and exposure to ART with non-communicable chronic diseases, we performed a cross-sectional analysis to evaluate the prevalence of comorbidities in patients enrolled in the SCOLTA Project, stratified by groups of chronological age (50-59 and 60-69 years) and by years of antiretroviral treatment (ART, <= 3 or > 3 years). Results In 1394 subjects (23.8% women), mean age at enrollment was 57.4 (SD 6.5) years, and at first ART 45.3 (SD 10.7). Men were older than women both at enrollment (57.6 vs 56.8, p = 0.06) and at first ART (45.8 vs 43.6, p = 0.0009). ART duration was longer in women (13.1 vs 11.7 years, p = 0.01). The age- and sex-adjusted rate ratios (aRRs, and 95% confidence interval, CI) showed that longer ART exposure was associated with dyslipidemia (aRR 1.35, 95% CI 1.20-1.52), hypertension (aRR 1.52, 95% CI 1.22-1.89), liver disease (aRR 1.78, 95% CI 1.32-2.41), osteopenia/osteoporosis (aRR 2.88, 95% CI 1.65-5.03) and multimorbidity (aRR 1.36, 95% CI 1.21-1.54). These findings were confirmed in strata of age, adjusting for sex. Conclusions Our data suggest that longer ART exposure was associated with increased risk of dyslipidemia, hypertension, and osteopenia/osteoporosis, hence the presence of multimorbidity, possibly due to the exposition to more toxic antiretrovirals. We observed different comorbidities, according to ART exposure and age

Fatality rate and predictors of mortality in an Italian cohort of hospitalized COVID-19 patients

Clinical features and natural history of coronavirus disease 2019 (COVID-19) differ widely among different countries and during different phases of the pandemia. Here, we aimed to evaluate the case fatality rate (CFR) and to identify predictors of mortality in a cohort of COVID-19 patients admitted to three hospitals of Northern Italy between March 1 and April 28, 2020. All these patients had a confirmed diagnosis of SARS-CoV-2 infection by molecular methods. During the study period 504/1697 patients died; thus, overall CFR was 29.7%. We looked for predictors of mortality in a subgroup of 486 patients (239 males, 59%; median age 71 years) for whom sufficient clinical data were available at data cut-off. Among the demographic and clinical variables considered, age, a diagnosis of cancer, obesity and current smoking independently predicted mortality. When laboratory data were added to the model in a further subgroup of patients, age, the diagnosis of cancer, and the baseline PaO2/FiO2 ratio were identified as independent predictors of mortality. In conclusion, the CFR of hospitalized patients in Northern Italy during the ascending phase of the COVID-19 pandemic approached 30%. The identification of mortality predictors might contribute to better stratification of individual patient risk

L'evolution thermique de l'As implante dans le Si : liens entre l'activite electrique et l'evolution structurale

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Size effect on high temperature variable range hopping in Al+ implanted 4H-SiC

The hole transport properties of heavily doped 4H-SiC (Al) layers with Al implanted concentrations of 3 × 1020 and 5 × 1020 cm-3 and annealed in the temperature range 1950-2100 °C, have been analyzed to determine the main transport mechanisms. This study shows that the temperature dependence of the resistivity (conductivity) may be accounted for by a variable range hopping (VRH) transport into an impurity band. Depending on the concentration of the implanted impurities and the post-implantation annealing treatment, this VRH mechanism persists over different temperature ranges that may extend up to room temperature. In this framework, two different transport regimes are identified, having the characteristic of an isotropic 3D VRH and an anisotropic nearly 2D VRH. The latter conduction mechanism appears to take place in a rather thick layer (about 400 nm) that is too large to induce a confinement effect of the carrier hops. The possibility that an anisotropic transport may be induced by a structural modification of the implanted layer because of a high density of basal plane stacking faults (SF) in the implanted layers is considered. The interpretation of the conduction in the heaviest doped samples in terms of nearly 2D VRH is supported by the results of the transmission electron microscopy (TEM) investigation on one of the 5 × 1020 cm-3 Al implanted samples of this study. In this context, the average separation between basal plane SFs, measured along the c-axis, which is orthogonal to the carrier transport during electrical characterization, appears to be in keeping with the estimated value of the optimal hopping length of the VRH theory. Conversely, no SFs are detected by TEM in a sample with an Al concentration of 1 × 1019 cm-3 where a 3D nearest neighbor hopping (NNH) transport is observed