Development of tailored high-performance and durable electrocatalysts for advanced PEM fuel cells

A family of novel carbon materials with intermediate surface area and varying morphology and surface chemistry were used to prepare Pt/C catalysts by two different preparation procedures; a chemical impregnation method and a microwave-assisted polyol method. The catalysts were thoroughly characterized, and their electrochemical performance and stability were investigated with rotating disc electrode (RDE) cyclic voltammetric (CV) measurements. The intermediate-surface-area carbon supports gave catalysts with much greater support stability than a widely used standard catalyst. The novel catalysts had lower electrochemical surface area than the reference, but their specific electrocatalytic activity towards the oxygen-reduction reaction (ORR) was much higher, and some of them also featured higher mass-specific ORR activity than the reference. The series of catalysts prepared by the microwave-assisted polyol method featured smaller Pt nanoparticles and higher activities than those prepared by impregnation. On the other hand, the impregnated catalysts showed better durability of the Pt particles. The most promising catalysts were selected and elaborated in further optimized preparation procedures to obtain quantities sufficient for their use in proton-exchange membrane fuel cells (PEMFCs).     

Stability of cutinase,wild type and mutants,in AOT reversed micellar system—effect of mixture components of alkyl esters production

BACKGROUND: Fusarium solani pisi cutinase was microencapsulated in reversed micelles of bis(2‐ethylhexyl) sodium sulfosuccinate (AOT) in isooctane for the production of alkyl esters, known as biodiesel; its stability in this system was also evaluated. Results using cutinase wild type and three mutants, L153Q, T179C and S54D, were compared. RESULTS: There is a loss of 45% of cutinase wild type activity when incubated in the micellar system for 3 h, indicating a denaturing effect of AOT towards the enzyme, and furthermore a loss of 90% of the activity is observed in the presence of methanol with only 10 min of incubation. In contrast, an improvement of cutinase performance was achieved when incubated with ethanol or butanol, indicating that these alcohols have a protective role regarding the enzyme. Mutant T179C displayed high stability in the presence of methanol with an activity loss of only 16%. CONCLUSIONS: Mutant T179C presented not only high resistance to the denaturing effect of AOT but also high stability in the presence of methanol. This is a promising biocatalyst for a continuous process. Copyright © 2010 Society of Chemical Industry     

Microemulsion Synthesis of Superparamagnetic Nanoparticles for Bioapplications

Superparamagnetic nanoparticles have seen increased potential in medical and environmental applications. Their preparation is traditionally made by the coprecipitation method, with limited control over the particle size distribution. Microemulsion methods could be advantageous due to the efficient control of the size, shape, and composition of the nanoparticles obtained. Water-in-oil (W/O) microemulsions consist of aqueous microdomains dispersed in a continuous oil phase, stabilized by surfactant molecules. These work as nanoreactors where the synthesis of the desired nanoparticles takes place through a co-precipitation chemical reaction. In this work, superparamagnetic magnetite nanoparticles with average diameters between 5.4 and 7.2 nm and large monodispersity have been synthesized through precipitation in a W/O microemulsion, with Cetyl Trimethyl Ammonium Bromide (CTAB) as a main surfactant, 1-butanol as a cosurfactant, and with 1-hexanol as the continuous oily phase. The optimization of the corresponding washing protocol has also been established since a strict control is required when using these materials for bioapplications. Their applicability in those has been proved by their encapsulation in liposomes, being tested as signal enhancers for lateral flow immunoassays by using the affinity neutravidin-biotin model system. Due to their magnetic behaviour, they were also tested for magnetic separation. These novel materials have been found to be useful for analytical applications requiring high sensitivity and the removal of interferences.     

The PI3Kδ Inhibitor Idelalisib Diminishes Platelet Function and Shows Antithrombotic Potential

Background: Clinical management of ischemic events and prevention of vascular disease is based on antiplatelet drugs. Given the relevance of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) as a candidate target in thrombosis, the main goal of the present study was to identify novel antiplatelet agents within the existing inhibitors blocking PI3K isoforms. Methods: We performed a biological evaluation of the pharmacological activity of PI3K inhibitors in platelets. The effect of the inhibitors was evaluated in intracellular calcium release and platelet functional assays, the latter including aggregation, adhesion, and viability assays. The in vivo drug antithrombotic potential was assessed in mice undergoing chemically induced arterial occlusion, and the associated hemorrhagic risk evaluated by measuring the tail bleeding time. Results: We show that PI3K Class IA inhibitors potently block calcium mobilization in human platelets. The PI3K p110δ inhibitor Idelalisib inhibits platelet aggregation mediated by ITAM receptors GPVI and CLEC-2, preferentially by the former. Moreover, Idelalisib also inhibits platelet adhesion and aggregation under shear and adhesion to collagen. Interestingly, an antithrombotic effect was observed in mice treated with Idelalisib, with mild bleeding effects at high doses of the drug. Conclusion: Idelalisib may have antiplatelet effects with minor bleeding effects, which provides a rationale to evaluate its antithrombotic efficacy in humans.     

PET and SPECT Imaging of the EGFR Family (RTK Class I) in Oncology

The human epidermal growth factor receptor family (EGFR-family, other designations: HER family, RTK Class I) is strongly linked to oncogenic transformation. Its members are frequently overexpressed in cancer and have become attractive targets for cancer therapy. To ensure effective patient care, potential responders to HER-targeted therapy need to be identified. Radionuclide molecular imaging can be a key asset for the detection of overexpression of EGFR-family members. It meets the need for repeatable whole-body assessment of the molecular disease profile, solving problems of heterogeneity and expression alterations over time. Tracer development is a multifactorial process. The optimal tracer design depends on the application and the particular challenges of the molecular target (target expression in tumors, endogenous expression in healthy tissue, accessibility). We have herein summarized the recent preclinical and clinical data on agents for Positron Emission Tomography (PET) and Single Photon Emission Tomography (SPECT) imaging of EGFR-family receptors in oncology. Antibody-based tracers are still extensively investigated. However, their dominance starts to be challenged by a number of tracers based on different classes of targeting proteins. Among these, engineered scaffold proteins (ESP) and single domain antibodies (sdAb) show highly encouraging results in clinical studies marking a noticeable trend towards the use of smaller sized agents for HER imaging.     

Infections and Immunotherapy in Lung Cancer: A Bad Relationship?

Infectious diseases represent a relevant issue in lung cancer patients. Bacterial and viral infections might influence the patients’ prognosis, both directly affecting the immune system and indirectly impairing the outcome of anticancer treatments, mainly immunotherapy. In this analysis, we aimed to review the current evidence in order to clarify the complex correlation between infections and lung cancer. In detail, we mainly explored the potential impact on immunotherapy outcome/safety of (1) bacterial infections, with a detailed focus on antibiotics; and (2) viral infections, discriminating among (a) human immune-deficiency virus (HIV), (b) hepatitis B/C virus (HBV-HCV), and (c) Sars-Cov-2. A series of studies suggested the prognostic impact of antibiotic therapy administration, timing, and exposure ratio in patients treated with immune checkpoint inhibitors, probably through an antibiotic-related microbiota dysbiosis. Although cancer patients with HIV, HBV, and HCV were usually excluded from clinical trials evaluating immunotherapy, some retrospective and prospective trials performed in these patient subgroups reported similar results compared to those described in not-infected patients, with a favorable safety profile. Moreover, patients with thoracic cancers are particularly at risk of COVID-19 severe outcomes and mortality. Few reports speculated about the prognostic implications of anticancer therapy, including immunotherapy, in lung cancer patients with concomitant Sars-Cov-2 infection, showing, to date, inconsistent results. The correlation between infectious diseases and immunotherapy remains to be further explored and clarified in the context of dedicated trials. In clinical practice, the accurate and prompt multidisciplinary management of lung cancer patients with infections should be encouraged in order to select the best treatment options for these patients, avoiding unexpected toxicities, while maintaining the anticancer effect.     

Kynurenine/Tryptophan Ratio as a Potential Blood-Based Biomarker in Non-Small Cell Lung Cancer

The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) degrade tryptophan (Trp) into kynurenine (Kyn) at the initial step of an enzymatic pathway affecting T cell proliferation. IDO1 is highly expressed in various cancer types and associated with poor prognosis. Nevertheless, the serum Kyn/Trp concentration ratio has been suggested as a marker of cancer-associated immune suppression. We measured Kyn and Trp in blood samples of a wide cohort of non-small-cell lung cancer (NSCLC) patients, before they underwent surgery, and analyzed possible correlations of the Kyn/Trp ratio with either IDO1 expression or clinical–pathological parameters. Low Kyn/Trp significantly correlated with low IDO1 expression and never-smoker patients; while high Kyn/Trp was significantly associated with older (≥68 years) patients, advanced tumor stage, and squamous cell carcinoma (Sqcc), rather than the adenocarcinoma (Adc) histotype. Moreover, high Kyn/Trp was associated, among the Adc group, with higher tumor stages (II and III), and, among the Sqcc group, with a high density of tumor-infiltrating lymphocytes. A trend correlating the high Kyn/Trp ratio with the probability of recurrences from NSCLC was also found. In conclusion, high serum Kyn/Trp ratio, associated with clinical and histopathological parameters, may serve as a serum biomarker to optimize risk stratification and therapy of NSCLC patients.     

Phasor‐FLIM analysis of Thioflavin T self‐quenching in Concanavalin amyloid fibrils

The formation of amyloid structures has traditionally been related to human neurodegenerative pathologies and, in recent years, the interest in these highly stable nanostructures was extended to biomaterial sciences. A common method to monitor amyloid growth is the analysis of Thioflavin T fluorescence. The use of this highly selective dye, diffused worldwide, allows mechanistic studies of supramolecular assemblies also giving back important insight on the structure of these aggregates. Here we present experimental evidence of self‐quenching effect of Thioflavin T in presence of amyloid fibrils. A significant reduction of fluorescence lifetime of this dye which is not related to the properties of analyzed amyloid structures is found. This result is achieved by coupling Fluorescence Lifetime Imaging Microscopy with phasor approach as suitable model‐free methods and constitute a serious warning that have to be taken in account if is dye is used for quantitative studies.     

Graphene and carbon nanotube structures supported on mesoporous xerogel carbon as catalysts for oxygen reduction reaction in proton-exchange-membrane fuel cells

Non-precious metal catalysts for the oxygen reduction reaction (ORR) in proton-exchange-membrane fuel cells (PEMFCs) were obtained by pyrolysis of iron citrate and polyacrylonitrile on mesoporous xerogel carbon support. Chemical-physical characterizations, electrochemical studies by the rotating disc electrode, and electrochemical tests in a PEMFC configuration demonstrated that the porosity of the pristine carbon promotes the formation of graphene and carbon nanotube structures featuring ORR catalytic activity.