Development of stimuli-responsive graphene-based yolk-shell magnetic nanoparticles for controlled release of anticancer drugs

Magnetic drug delivery systems have attracted much attention in the last decades due to the possibility to improve the therapeutic efficacy of anticancer drugs, by enabling instable and poorly soluble drug agents to reach tumour cells after being guided by low magnetic fields and monitored by magnetic resonance imaging (MRI) [1]. Hence, a lower amount of anticancer drug is needed and the typical side effects of chemotherapy are minimized [2]. Commonly, these nanoparticles are designed with a magnetic core coated with a metal or a non-metal structure, such as gold or silica. However, these approaches present some drawbacks, such as low drug loading capacity and lack of stimuli-responsive release. Alternatively, carbon-coated magnetic nanoparticles offer higher chemical and thermal stability, larger surface area, biocompatibility and easier functionalization due to the high capacity of adsorption. Moreover, these materials have shown great ability to be used as pH stimuli-responsive controlled release platforms, due to the disruption of supramolecular interaction at acidic pH [3]. In this context, graphene-coated yolk-shell magnetic nanoparticles – hybrid materials comprising a superparamagnetic core coated by a graphene-based shell that covers a hollow region (i.e., Fe3O4@void@C), – were developed as super-drug nanocarriers systems, exhibiting high loading contents of the anticancer drug Doxorubicin due to the large cavity volume between the shell and the magnetic core, and a stimuliresponsive controlled release in response to acidic environments (pH 5), such as those found in tumour tissues. These results shed light on the development of new hybrid nanomaterials with high potential to be applied in biomedical applications.info:eu-repo/semantics/publishedVersio

Multifunctional graphene-based magnetic nanocarriers for combined hyperthermia and dual stimuli-responsive drug delivery

The synthesis of hydrophilic graphene-based yolk-shell magnetic nanoparticles functionalized with copolymer pluronic F-127 (GYSMNP@PF127) is herein reported to achieve an efficient multifunctional biomedical system for mild hyperthermia and stimuli-responsive drug delivery. In vitro tests revealed the extraordinary ability of GYSMNP@PF127 to act as smart stimuli-responsive multifunctional nanomedicine platform for cancer therapy, exhibiting (i) an outstanding loading capacity of91% (w/w,representing 910μgmg−1) of the chemotherapeutic drug doxorubicin, (ii) a high heating efficiency under an alternating (AC) magnetic field (intrinsic power loss ranging from 2.1–2.7nHm2kg−1), and (iii) a dual pH and thermal stimuli-responsive drug controlled release (46% at acidic tumour pH vs 7% at physiological pH) under AC magnetic field, in just 30min. Additionally, GYSMNP@PF127 presents optimal hydrodynamic diameter (DH=180nm) with negative surface charge, high haemocompatibility for blood stream applications and tumour cellular uptake of drug nanocarriers. Due to its physicochemical, magnetic and biocompatibility properties, the developed graphene-based magnetic nanocarrier shows high promise as dual exogenous (AC field)/endogenous (pH) stimuli-responsive actuators for targeted thermo-chemotherapy, combining magnetic hyperthermia and controlled drug release triggered by the abnormal tumour environment. The presented strategy and findings can represent a new way to design and develop highly stable added-value graphene-based nanostructures for the combined treatment of cancer.This work was financially supported by: Project POCI-01-0145- FEDER-006984 – Associate Laboratory LSRE-LCM funded by FEDER through COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI) – and by national funds through FCT - Fundação para a Ciência e a Tecnologia, and by project NORTE-01- 0145-FEDER-029394, RTChip4Theranostics, supported by Programa Operacional Regional do Norte - Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) and by Fundação para a Ciência e Tecnologia (FCT), IP. R.O.R. acknowledges the Ph.D. scholarship SFRH/BD/97658/2013 granted by FCT. A.M.T.S acknowledges the FCT Investigator 2013 Programme (IF/ 01501/2013), with financing from the European Social Fund and the Human Potential Operational Programme. G.D. acknowledges financing by Slovene Research Agency (J2-6754). M. B. acknowledges financial funding from POCTEP (Co-operational Programme for Crossborder Cooperation Spain-Portugal). This article is based upon work from COST Action RADIOMAG (TD1402), supported by COST (European Cooperation in Science and Technology).info:eu-repo/semantics/publishedVersio

The threshold hypothesis revisited: bilingual lexical knowledge and non-verbal IQ development

The threshold hypothesis (Cummins 1976 et passim) is one of the most influential theoretical frameworks on the relation between bilingualism and cognition. The aim of our study is to contribute towards an operationalisation of the threshold hypothesis. We analyse data from 100 Turkish-English successive bilingual children and from their parents, and investigate the relation between bilingualism and cognition. When compared with monolingual control groups, the bilinguals in our study have smaller vocabulary sizes in both languages. However, when both vocabularies are taken together and the total conceptual vocabulary is computed no bilingual disadvantage can be identified. Children with parental support for L1 outperform the monolingual control groups in our study in terms of non-verbal intelligence scores. The originality of the present study resides in the fact that, to our knowledge, for the first time parental support for L1 and dominance in L1 is linked to the cognitive development of the children

A tailor-made protocol to synthesize yolk-shell graphene-based magnetic nanoparticles for nanomedicine

A simple tailor-made protocol to synthesize graphene-based magnetic nanoparticles (GbMNPs) for nanomedicine is herein reported. Different GbMNPs with very distinctive physicochemical and toxicological properties were synthesized by adjusting the number of carbon precursors in the coating of superparamagnetic iron oxide nanoparticles. In vitro tests show the ability to use these GbMNPs as intelligent and on-demand drug nanocarrier systems for drug delivery, exhibiting the following features: good colloidal stability, good loading capacity of the chemotherapeutic drug doxorubicin, high pH-controlled release of the encapsulated drug (targeting tumour acidic pH conditions), superparamagnetic behaviour and biocompatibility. Due to their combined properties (i.e., physicochemical, magnetic, and biocompatibility), GbMNPs show high potentiality to be combined with other biomedical techniques, such as magnetic hyperthermia, which can represent an enhancement in the treatment of cancer.This research was funded by Project POCI-01-0145-FEDER-006984 - Associate Laboratory LSRE-LCM funded by FEDER through COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI) - and by national funds through FCT - Fundação para a Ciência e a Tecnologia, and by project NORTE-01-0145-FEDER-029394, RTChip4Theranostics, supported by Programa Operacional Regional do Norte - Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) and by Fundação para a Ciência e Tecnologia (FCT), IP.R.O.R. acknowledges the Ph.D. scholarship SFRH/BD/97658/2013 granted by FCT. G.D. acknowledges financing by Slovene Research Agency (J2-6754). The authors also would like to acknowledge the financial support provided by COST—European Cooperation in Science and Technology, in the form of a short term scientific mission (STSM) granted by COST Action TD1402: RADIOMAG.info:eu-repo/semantics/publishedVersio

Circadian clock mechanism driving mammalian photoperiodism

From Springer Nature via Jisc Publications RouterHistory: received 2020-01-16, accepted 2020-07-27, registration 2020-08-04, pub-electronic 2020-08-27, online 2020-08-27, collection 2020-12Publication status: PublishedAbstract: The annual photoperiod cycle provides the critical environmental cue synchronizing rhythms of life in seasonal habitats. In 1936, Bünning proposed a circadian-based coincidence timer for photoperiodic synchronization in plants. Formal studies support the universality of this so-called coincidence timer, but we lack understanding of the mechanisms involved. Here we show in mammals that long photoperiods induce the circadian transcription factor BMAL2, in the pars tuberalis of the pituitary, and triggers summer biology through the eyes absent/thyrotrophin (EYA3/TSH) pathway. Conversely, long-duration melatonin signals on short photoperiods induce circadian repressors including DEC1, suppressing BMAL2 and the EYA3/TSH pathway, triggering winter biology. These actions are associated with progressive genome-wide changes in chromatin state, elaborating the effect of the circadian coincidence timer. Hence, circadian clock-pituitary epigenetic pathway interactions form the basis of the mammalian coincidence timer mechanism. Our results constitute a blueprint for circadian-based seasonal timekeeping in vertebrates

The NORMAN Suspect List Exchange (NORMAN-SLE): facilitating European and worldwide collaboration on suspect screening in high resolution mass spectrometry

Background: The NORMAN Association (https://www.norman-.network.com/) initiated the NORMAN Suspect List Exchange (NORMAN-SLE; https://www.norman-.network.com/nds/SLE/) in 2015, following the NORMAN collaborative trial on non-target screening of environmental water samples by mass spectrometry. Since then, this exchange of information on chemicals that are expected to occur in the environment, along with the accompanying expert knowledge and references, has become a valuable knowledge base for "suspect screening" lists. The NORMAN-SLE now serves as a FAIR (Findable, Accessible, Interoperable, Reusable) chemical information resource worldwide.Results: The NORMAN-SLE contains 99 separate suspect list collections (as of May 2022) from over 70 contributors around the world, totalling over 100,000 unique substances. The substance classes include per- and polyfluoroalkyl substances (PFAS), pharmaceuticals, pesticides, natural toxins, high production volume substances covered under the European REACH regulation (EC: 1272/2008), priority contaminants of emerging concern (CECs) and regulatory lists from NORMAN partners. Several lists focus on transformation products (TPs) and complex features detected in the environment with various levels of provenance and structural information. Each list is available for separate download. The merged, curated collection is also available as the NORMAN Substance Database (NORMAN SusDat). Both the NORMAN-SLE and NORMAN SusDat are integrated within the NORMAN Database System (NDS). The individual NORMAN-SLE lists receive digital object identifiers (DOIs) and traceable versioning via a Zenodo community (https:// zenodo.org/communities/norman-.sle), with a total of > 40,000 unique views, > 50,000 unique downloads and 40 citations (May 2022). NORMAN-SLE content is progressively integrated into large open chemical databases such as PubChem (https://pubchem.ncbi.nlm.nih.gov/) and the US EPA's CompTox Chemicals Dashboard (https://comptox. epa.gov/dashboard/), enabling further access to these lists, along with the additional functionality and calculated properties these resources offer. PubChem has also integrated significant annotation content from the NORMAN-SLE, including a classification browser (https://pubchem.ncbi.nlm.nih.gov/classification/#hid=101).Conclusions: The NORMAN-SLE offers a specialized service for hosting suspect screening lists of relevance for the environmental community in an open, FAIR manner that allows integration with other major chemical resources. These efforts foster the exchange of information between scientists and regulators, supporting the paradigm shift to the "one substance, one assessment" approach. New submissions are welcome via the contacts provided on the NORMAN-SLE website (https://www.norman-.network.com/nds/SLE/)

A multi-criteria sustainability assessment framework: development and application in comparing two food waste management options using a UK region as a case study

This is a post-peer-review, pre-copyedit version of an article published in Environmental Science and Pollution Research. The final authenticated version is available online at: https://doi.org/10.1007/s11356-018-2479-

The NORMAN Suspect List Exchange (NORMAN-SLE): Facilitating European and worldwide collaboration on suspect screening in high resolution mass spectrometry

Background: The NORMAN Association (https://www.norman-network.com/) initiated the NORMAN Suspect List Exchange (NORMAN-SLE; https://www.norman-network.com/nds/SLE/) in 2015, following the NORMAN collaborative trial on non-target screening of environmental water samples by mass spectrometry. Since then, this exchange of information on chemicals that are expected to occur in the environment, along with the accompanying expert knowledge and references, has become a valuable knowledge base for “suspect screening” lists. The NORMAN-SLE now serves as a FAIR (Findable, Accessible, Interoperable, Reusable) chemical information resource worldwide. Results: The NORMAN-SLE contains 99 separate suspect list collections (as of May 2022) from over 70 contributors around the world, totalling over 100,000 unique substances. The substance classes include per- and polyfluoroalkyl substances (PFAS), pharmaceuticals, pesticides, natural toxins, high production volume substances covered under the European REACH regulation (EC: 1272/2008), priority contaminants of emerging concern (CECs) and regulatory lists from NORMAN partners. Several lists focus on transformation products (TPs) and complex features detected in the environment with various levels of provenance and structural information. Each list is available for separate download. The merged, curated collection is also available as the NORMAN Substance Database (NORMAN SusDat). Both the NORMAN-SLE and NORMAN SusDat are integrated within the NORMAN Database System (NDS). The individual NORMAN-SLE lists receive digital object identifiers (DOIs) and traceable versioning via a Zenodo community (https://zenodo.org/communities/norman-sle), with a total of > 40,000 unique views, > 50,000 unique downloads and 40 citations (May 2022). NORMAN-SLE content is progressively integrated into large open chemical databases such as PubChem (https://pubchem.ncbi.nlm.nih.gov/) and the US EPA’s CompTox Chemicals Dashboard (https://comptox.epa.gov/dashboard/), enabling further access to these lists, along with the additional functionality and calculated properties these resources offer. PubChem has also integrated significant annotation content from the NORMAN-SLE, including a classification browser (https://pubchem.ncbi.nlm.nih.gov/classification/#hid=101). Conclusions: The NORMAN-SLE offers a specialized service for hosting suspect screening lists of relevance for the environmental community in an open, FAIR manner that allows integration with other major chemical resources. These efforts foster the exchange of information between scientists and regulators, supporting the paradigm shift to the “one substance, one assessment” approach. New submissions are welcome via the contacts provided on the NORMAN-SLE website (https://www.norman-network.com/nds/SLE/)