Electrochemically Controlled Cleavage of Imine Bonds on a Graphene Platform: Towards New Electro-Responsive Hybrids for Drug Release

[Abstract] Graphene-based materials are particularly suitable platforms for the development of new systems able to release drugs upon the application of controlled electrochemical stimuli. Herein, we report a new electro-responsive graphene carrier functionalised with aldehydes (as drug models) through imine-based linkers. We explore a new type of drug loading/release combination based on the formation of a covalent bond and its cleavage upon electrolysis. The new graphene–drug model hybrid is stable under physiological conditions and displays a fast drug release upon the application of low voltages.M. Prato is the recipient of the AXA Chair (2016–2023). A. Criado, H.-L. Hou and D. Mancino thank MINECO for their research grants (Juan de la Cierva – Incorporación No. IJCI-2016-31113 and IJC-2018-037396 for A. Criado and H.-L. Hou, respectively; and FPI No. BES-2017-081563 for D. Mancino). This work was supported by the Graphene Flagship Core 2 and Core 3 grant agreement (No. 785219 and 881603, respectively) and EU H2020-MSCA-RISE-2016 (No. 734381). This work was performed under the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency – Grant No. MDM-2017-0720

A novel method to identify and characterise peptide mimotopes of heat shock protein 70-associated antigens

The heat shock protein, Hsp70, has been shown to play an important role in tumour immunity. Vaccination with Hsp70-peptide complexes (Hsp70-PCs), isolated from autologous tumour cells, can induce protective immune responses. We have developed a novel method to identify synthetic mimic peptides of Hsp70-PCs and to test their ability to activate T-cells. Peptides (referred to as "recognisers") that bind to Hsp70-PCs from the human breast carcinoma cell line, MDA-MB-231, were identified by bio-panning a random peptide M13 phage display library. Synthetic recogniser peptides were subsequently used as bait in a reverse bio-panning experiment to identify potential Hsp70-PC mimic peptides. The ability of the recogniser and mimic peptides to prime human lymphocyte responses against tumour cell antigens was tested by stimulating lymphocytes with autologous peptide-loaded monocyte-derived dendritic cells (DCs). Priming and subsequent stimulation with either the recogniser or mimic peptide resulted in interferon-γ (IFN-γ) secretion by the lymphocytes. Furthermore, DCs loaded with Hsp70, Hsp70-PC or the recogniser or the mimic peptide primed the lymphocytes to respond to soluble extracts from breast cells. These results highlight the potential application of synthetic peptide-mimics of Hsp70-PCs, as modulators of the immune response against tumours

Influence of Feedstock Particle Size on the Certain Determination of Chlorine and Bromine in Pyrolysis Oils from Waste Electrical and Electronic Equipment Plastics

Rejected streams emerging from waste sorting and recycling plants are still capable of being valorized by unconventional recycling routes. This is the case of the plastic-rich fraction generated after the treatment of waste electrical and electronic equipment (WEEE). However, the material complexity of this stream supposes a handicap when it comes to obtaining repetitive results in laboratory-scale recycling processes. This work aims to highlight the influence that the pretreatment (mainly particle size reduction) of a real WEEE plastic-rich stream has on the variability of the concentration of halogens (representative pollutants) in the oils obtained from its recycling via pyrolysis. The pretreatment steps were based on the standards of the European Committee for Standardization (ECN) for the analysis of waste samples. Four samples were studied: the WEEE plastics as received; two milled samples (2 and 1 mm particle size) derived from the original one; and a simulated sample composed of virgin polymers. All the samples were treated under the same conditions: 500 °C reaction temperature, 15 °C min–1 heating rate, 30 min dwell time, and a 1 L min–1 nitrogen purge flow. The oils obtained in, at least, two pyrolysis tests performed on the same sample were deeply characterized, and the results were compared. The oils derived from the “as-received” sample showed an unacceptable relative standard deviation (RSD, ∼42%) in the chlorine concentration. The sample milled to 2 mm reduced the RSD on the concentration of chlorine in the oils down to 8%, while no enhancement in the results was observed for the further milled sample. The other two major pyrolysis fractions were also characterized, showing an overall enhancement in the RSD of the analysis of the main components of the gases, while no improvement in the solids pollutants’ characterization was achieved.This research was funded by the Basque Government through the project with reference KK-2023/00060 (ELKARTEK program), and through the support of the SUPREN research group (IT993-16 and IT1554-22). The authors also want to thank the University of the Basque Country (UPV/EHU) for the funding of the PIF21/296 grant. Finally, SGIker technical and human support (UPV/EHU, MICINN, GV/EJ, ESF) is gratefully acknowledged

The Effect of Different Oxygen Surface Functionalization of Carbon Nanotubes on the Electrical Resistivity and Strain Sensing Function of Cement Pastes

Different studies in the literature indicate the effectiveness of CNTs as reinforcing materials in cement–matrix composites due to their high mechanical strength. Nevertheless, their incorporation into cement presents some difficulties due to their tendency to agglomerate, yielding a non-homogeneous dispersion in the paste mix that results in a poor cement–CNTs interaction. This makes the surface modification of the CNTs by introducing functional groups on the surface necessary. In this study, three different treatments for incorporating polar oxygen functional groups onto the surface of carbon nanotubes have been carried out, with the objective of evaluating the influence of the type and oxidation degree on the mechanical and electrical properties and in strain-sensing function of cement pastes containing CNTs. One treatment is in liquid phase (surface oxidation with HNO3/H2SO4), the second is in gas phase (O3 treatment at 25 and 160 °C), and a third is a combination of gas-phase O3 treatment plus NaOH liquid phase. The electrical conductivity of cement pastes increased with O3- and O3-NaOH-treated CNTs with respect to non-treated ones. Furthermore, the oxygen functionalization treatments clearly improve the strain sensing performance of the CNT-cement pastes, particularly in terms of the accuracy of the linear correlation between the resistance and the stress, as well as the increase in the gage factor from 28 to 65. Additionally, the incorporation of either non-functionalized or functionalized CNTs did not produce any significant modification of the mechanical properties of CNTs. Therefore, the functionalization of CNTs favours the de-agglomeration of CNTs in the cement matrix and consequently, the electrical conductivity, without affecting the mechanical behaviour.This research was funded by the European Union’s Horizon 2020 Research and Innovation Programme, grant number 760940

Decellularization of xenografted tumors provides cell-specific in vitro 3D environment

In vitro cell culture studies are common in the cancer research field, and reliable biomimetic 3D models are needed to ensure physiological relevance. In this manuscript, we hypothesized that decellularized xenograft tumors can serve as an optimal 3D substrate to generate a top-down approach for in vitro tumor modeling. Multiple tumor cell lines were xenografted and the formed solid tumors were recovered for their decellularization by several techniques and further characterization by histology and proteomics techniques. Selected decellularized tumor xenograft samples were seeded with the HCC1806 human triple-negative breast cancer (TNBC) basal-like subtype cell line, and cell behavior was compared among them and with other control 2D and 3D cell culture methods. A soft treatment using Freeze-EDTA-DNAse allows proper decellularization of xenografted tumor samples. Interestingly, proteomic data show that samples decellularized from TNBC basal-like subtype xenograft models had different extracellular matrix (ECM) compositions compared to the rest of the xenograft tumors tested. The in vitro recellularization of decellularized ECM (dECM) yields tumor-type–specific cell behavior in the TNBC context. Data show that dECM derived from xenograft tumors is a feasible substrate for reseeding purposes, thereby promoting tumor-type–specific cell behavior. These data serve as a proof-of-concept for further potential generation of patient-specific in vitro research models.Grant RTI2018-101708-A-I00 funded by MCIN/AEI/10.13039/501100011033 and by ERDF A way of making Europe. Grants RYC2018-025502-I and PRE2018-084542 are funded by MCIN/AEI/10.13039/501100011033 and by ESF Investing in your future. Grant MDM-2017-0720 Maria de Maeztu Units of Excellence Program funded by the Spanish State Research Agency. Grant KK-2019/00093 Elkartek program funded by Basque Government. Grant CICBMG_PhD_03_2021 funded by CICbiomaGUNE and Polymat. Grant CICBMG_PhD_05_2019 funded by CICbiomaGUNE and Polymat. 2019 Leonardo Grant for Researchers and Cultural Creators, BBVA Foundation, grant number IN[19]_CMA_BIO_0119. The BBVA Foundation accepts no responsibility for the opinions, statements, and contents included, which are entirely the responsibility of the authors

Investigación en Danza CSIC

INVESTIGACIÓN EN DANZA CSIC es un portal que recoge la actividad científica sobre danza en el contexto del Instituto de Historia del Consejo Superior de Investigaciones Científicas, sus proyectos de investigación e iniciativas vinculadasPeer reviewe

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio