Biomimetic platelet membrane-coated nanoparticles for targeted therapy

The development of cell membrane-modified biomimetic nanoparticles has extensively increased during the past years due to their exceptional biocompatibility, evasion from the immune system, and targeting ability. Known as a cutting-edge area of research in nanomedicine, such novel nanoplatforms can mimic different functions of the primary cells, while successfully delivering their cargos to the defect site with the aim of enhancing the therapeutic responses and reducing the side effects. Platelet is a key factor for haemostasis and a major player in wound healing, inflammation, and many other biological functions and pathological conditions. As a highly responsive cell, platelets can adapt to environment modifications and release several soluble biomolecules, such as growth factors, coagulant factors, and extracellular vesicles. Additionally, platelets are capable of immune system evasion, sub-endothelial adhesion, and pathogen interaction. These characteristics have inspired the design of several platelet membrane-coated nanoparticles as drug delivery systems. This review describes the current developments in platelet membrane-coated nanoparticles for targeted therapy, specifically, their advantages compared to other biomimetic cell-derived nanoparticles and their applicability in the medical field are elucidated. Finally, the challenges and future perspectives associated with this nanoplatform are summarised.Peer reviewe

Inflationary signatures of single-field models beyond slow-roll

If the expansion of the early Universe was not close to de Sitter, the statistical imprints of the primordial density perturbation on the cosmic microwave background can be quite different from those derived in slow-roll inflation. In this paper we study the inflationary signatures of all single-field models which are free of ghost-like instabilities. We allow for a rapid change of the Hubble parameter and the speed of sound of scalar fluctuations, in a way that is compatible with a nearly scale-invariant spectrum of perturbations, as supported by current cosmological observations. Our results rely on the scale-invariant approximation, which is different from the standard slow-roll approximation. We obtain the propagator of scalar fluctuations and compute the bispectrum, keeping next-order corrections proportional to the deviation of the spectral index from unity. These theories offer an explicit example where the shape and scale-dependences of the bispectrum are highly non-trivial whenever slow-roll is not a good approximation.Comment: v1: 36 pages, including tables, appendices and references. v2: abstract improved, references added, minor clarifications throughout the text; matches version published in JCA

The δN formula is the dynamical renormalization group

We derive the 'separate universe' method for the inflationary bispectrum, beginning directly from a field-theory calculation. We work to tree-level in quantum effects but to all orders in the slow-roll expansion, with masses accommodated perturbatively. Our method provides a systematic basis to account for novel sources of time-dependence in inflationary correlation functions, and has immediate applications. First, we use our result to obtain the correct matching prescription between the 'quantum' and 'classical' parts of the separate universe computation. Second, we elaborate on the application of this method in situations where its validity is not clear. As a by-product of our calculation we give the leading slow-roll corrections to the three-point function of field fluctuations on spatially flat hypersurfaces in a canonical, multiple-field model.Comment: v1: 33 pages, plus appendix and references; 5 figures. v2: typographical typos fixed, minor changes to the main text and abstract, reference added; matches version published in JCA

práticas artísticas no ensino básico e secundário

Educação Artística: integrar a inovação. A educação artística apresenta-se como um território a re-cartografar, numa atualização tão rápida quanto aquela que ocorre no campo artístico. As propostas publicadas neste número 11 da Revista Matéria-Prima trazem essa diversidade de abordagens, com novidades conceptuais que estabelecem as devidas relações entre educação e cidadania, participação, sustentabilidade, cultura visual, e também com alguma atenção sobre os debates pós-coloniais e as questões de género. Os 16 artigos reunidos neste 11º número da Revista Matéria-Prima trazem a realidade operativa quer na formação de professores e quer na formulação dos discursos pedagógicos, suas justificações e suas propostas alternativas.As propostas apresentadas devolvem o debate ao terreno, e alargam-no. Provocam as periferias, convocam abordagens diferenciadas sobre o tema da arte e da educação. Em todas elas a proposta de crescimento através da arte, que hoje implica cada vez mais cidadania, crítica, criatividade, interligação, comprometimento, participação.info:eu-repo/semantics/publishedVersio

Novel missense mutations affecting the structure of the conserved fibrinogen Bβ C-terminal domain cause congenital hypofibrinogenemia

This study describes the identification of two new mutations of the fibrinogen beta-chain in patients with inherited fibrinogen deficiency. Modelling of the impact of the mutations predict that these single amino acid substitutions are sufficient to abolish secretion of the mutant chains into the circulation, resulting in low fibrinogen levels in the patients. In addition, whole exome sequencing identified genetic modifiers for both patients which could contribute to the patients' global hemostatic function. Our results yield clinically relevant information for the personalised management of patients and eventually precision medicine for fibrinogen disorders

Injectable Nanocomposite Hydrogels of Gelatin-Hyaluronic Acid Reinforced with Hybrid Lysozyme Nanofibrils-Gold Nanoparticles for the Regeneration of Damaged Myocardium

Biopolymeric injectablehydrogels are promising biomaterialsformyocardial regeneration applications. Besides being biocompatible,they adjust themselves, perfectly fitting the surrounding tissue.However, due to their nature, biopolymeric hydrogels usually lackdesirable functionalities, such as antioxidant activity and electricalconductivity, and in some cases, mechanical performance. Protein nanofibrils(NFs), such as lysozyme nanofibrils (LNFs), are proteic nanostructureswith excellent mechanical performance and antioxidant activity, whichcan work as nanotemplates to produce metallic nanoparticles. Here,gold nanoparticles (AuNPs) were synthesized in situ in the presenceof LNFs, and the obtained hybrid AuNPs@LNFs were incorporated intogelatin-hyaluronic acid (HA) hydrogels for myocardial regenerationapplications. The resulting nanocomposite hydrogels showed improvedrheological properties, mechanical resilience, antioxidant activity,and electrical conductivity, especially for the hydrogels containingAuNPs@LNFs. The swelling and bioresorbability ratios of these hydrogelsare favorably adjusted at lower pH levels, which correspond to theones in inflamed tissues. These improvements were observed while maintainingimportant properties, namely, injectability, biocompatibility, andthe ability to release a model drug. Additionally, the presence ofAuNPs allowed the hydrogels to be monitorable through computer tomography.This work demonstrates that LNFs and AuNPs@LNFs are excellent functionalnanostructures to formulate injectable biopolymeric nanocompositehydrogels for myocardial regeneration applications.Peer reviewe

Management practices for postdural puncture headache in obstetrics : a prospective, international, cohort study

Background: Accidental dural puncture is an uncommon complication of epidural analgesia and can cause postdural puncture headache (PDPH). We aimed to describe management practices and outcomes after PDPH treated by epidural blood patch (EBP) or no EBP. Methods: Following ethics committee approval, patients who developed PDPH after accidental dural puncture were recruited from participating countries and divided into two groups, those receiving EBP or no EBP. Data registered included patient and procedure characteristics, headache symptoms and intensity, management practices, and complications. Follow-up was at 3 months. Results: A total of 1001 patients from 24 countries were included, of which 647 (64.6%) received an EBP and 354 (35.4%) did not receive an EBP (no-EBP). Higher initial headache intensity was associated with greater use of EBP, odds ratio 1.29 (95% confidence interval 1.19-1.41) per pain intensity unit increase. Headache intensity declined sharply at 4 h after EBP and 127 (19.3%) patients received a second EBP. On average, no or mild headache (numeric rating score <= 3) was observed 7 days after diagnosis. Intracranial bleeding was diagnosed in three patients (0.46%), and backache, headache, and analgesic use were more common at 3 months in the EBP group. Conclusions: Management practices vary between countries, but EBP was more often used in patients with greater initial headache intensity. EBP reduced headache intensity quickly, but about 20% of patients needed a second EBP. After 7 days, most patients had no or mild headache. Backache, headache, and analgesic use were more common at 3 months in patients receiving an EBP