Comparison of “IN-REC-SUR-E” and LISA in preterm neonates with respiratory distress syndrome: a randomized controlled trial (IN-REC-LISA trial)

Background: Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. Methods: In this study, 382 infants born at 24+0–27+6 weeks’ gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks’ postmenstrual age. The secondary outcomes are BPD at 36 weeks’ postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). Discussion: This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0–27+6 weeks’ gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks’ postmenstrual age of life. Trial registration: ClinicalTrials.gov NCT05711966. Registered on February 3, 2023

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Accumulation of styrene oligomers alters lipid membrane phase order and miscibility

Significance Accumulation of nanopollutants in lifeforms has become the subject of increasing concern, but effects are not understood. Biological systems are inherently complex, and therefore any small variations on the membrane properties can potentially perturb cell functionality. In this study we observe that the presence of styrene oligomers in lipid membranes alters their phase behavior, with stronger changes occurring in more complex systems, which could translate into potential cellular disruption. This study provides evidence that the presence of nanopollutants in the membrane may alter its fundamental properties and affect cell viability.</jats:p

DPPC Bilayers in Solutions of High Sucrose Content

International audienceThe properties of lipid bilayers in sucrose solutions have been intensely scrutinized over recent decades because of the importance of sugars in the field of biopreservation. However, a consensus has not yet been formed on the mechanisms of sugar-lipid interaction. Here, we present a study on the effect of sucrose on 1,2-dipalmitoyl-sn-glycero-3-phos-phocholine bilayers that combines calorimetry, spectral fluorimetry, and optical microscopy. Intriguingly, our results show a significant decrease in the transition enthalpy but only a minor shift in the transition temperature. Our observations can be quantitatively accounted for by a thermodynamic model that assumes partial delayed melting induced by sucrose adsorption at the membrane interface

Guanidinium Like‐Charge Ion Pairing and Oligoarginine Aggregation in Water by Nuclear Magnetic Resonance, Cryo‐Electron Microscopy, and Molecular Dynamics

ABSTRACT Like‐charge pairing is a physical manifestation of the unique solvation properties of certain ion pairs in water. Water's high dielectric constant and related charge screening capability significantly influence the interaction between like‐charged ions, with the possibility to transform it—in exceptional cases when noncovalent interactions are involved—from repulsion to attraction. Guanidinium cations (Gdm+) represent a quintessential example of such like‐charge pairing due to their specific geometry and electronic structure. In this work, we present experimental validation and quantification of Gdm+–Gdm+ contact ion pairing in water utilizing nuclear magnetic resonance (NMR) spectroscopy complemented by molecular dynamics (MD) simulations and density functional theory (DFT) calculations. The observed Gdm+–Gdm+ interaction is attractive albeit weak—about −0.5 kJ·mol−1 —which aligns with theoretical estimation from MD simulations. We contrast the behavior of Gdm+ with that of NH4+ cations, which exhibit no contact ion pairing in water. DFT calculations predict that the NMR chemical shift of Gdm+ dimers is different than that of monomers, in agreement with NMR titration curves that display a nonlinear Langmuir‐like behavior. Additionally, we conducted cryo‐electron microscopy—to our knowledge, for the first time—on concentrated oligoarginines R9, which, unlike nona‐lysines K9, exhibit aggregation in water. These results point to like charge pairing of the guanidinium side chain groups, as corroborated also by MD simulations and free energy calculations

Genetically engineered MRI-trackable extracellular vesicles as SARS-CoV-2 mimetics for mapping ACE2 binding <i>in vivo</i>

AbstractThe elucidation of viral-receptor interactions and an understanding of virus-spreading mechanisms are of great importance, particularly in the era of pandemic. Indeed, advances in computational chemistry, synthetic biology, and protein engineering have allowed precise prediction and characterization of such interactions. Nevertheless, the hazards of the infectiousness of viruses, their rapid mutagenesis, and the need to study viral-receptor interactions in a complex in vivo setup, call for further developments. Here, we show the development of biocompatible genetically engineered extracellular vesicles (EVs) that display the receptor binding domain (RBD) of SARS-CoV-2 on their surface as coronavirus mimetics (EVsRBD). Loading EVsRBD with iron oxide nanoparticles makes them MRI-visible, and thus, allows mapping of the binding of RBD to ACE2 receptors non-invasively in live subjects. Importantly, the proposed mimetics can be easily modified to display the RBD of SARS-CoV-2mutants, namely Delta and Omicron, allowing rapid screening of newly raised variants of the virus. The proposed platform thus shows relevance and cruciality in the examination of quickly evolving pathogenic viruses in an adjustable, fast, and safe manner.</jats:p

Migration of Deformable Vesicles Induced by Ionic Stimuli

We have investigated the dynamics of phospholipid vesicles composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine triggered by ionic stimuli using electrolytes such as CaCl2, NaCl, and NaOH. The ionic stimuli induce two characteristic vesicle dynamics, deformation due to the ion binding to the lipids in the outer leaflet of the vesicle and migration due to the concentration gradient of ions, that is, diffusiophoresis or the interfacial energy gradient mechanism. We examined the deformation pathway for each electrolyte as a function of time and analyzed it based on the surface dissociation model and the area difference elasticity model, which reveals the change of the cross-sectional area of the phospholipid by the ion binding. The metal ions such as Ca2+ and Na+ encourage inward budding deformation by decreasing the cross-sectional area of a lipid, whereas the hydroxide ion (OH–) encourages outward budding deformation by increasing the cross-sectional area of a lipid. When we microinjected these electrolytes toward the vesicles, a strong coupling between the deformation and the migration of the vesicle was observed for CaCl2 and NaOH, whereas for NaCl, the coupling was very weak. This difference probably originates from the binding constants of the ions

Migration of Deformable Vesicles Induced by Ionic Stimuli

We have investigated the dynamics of phospholipid vesicles composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine triggered by ionic stimuli using electrolytes such as CaCl2, NaCl, and NaOH. The ionic stimuli induce two characteristic vesicle dynamics, deformation due to the ion binding to the lipids in the outer leaflet of the vesicle and migration due to the concentration gradient of ions, that is, diffusiophoresis or the interfacial energy gradient mechanism. We examined the deformation pathway for each electrolyte as a function of time and analyzed it based on the surface dissociation model and the area difference elasticity model, which reveals the change of the cross-sectional area of the phospholipid by the ion binding. The metal ions such as Ca2+ and Na+ encourage inward budding deformation by decreasing the cross-sectional area of a lipid, whereas the hydroxide ion (OH–) encourages outward budding deformation by increasing the cross-sectional area of a lipid. When we microinjected these electrolytes toward the vesicles, a strong coupling between the deformation and the migration of the vesicle was observed for CaCl2 and NaOH, whereas for NaCl, the coupling was very weak. This difference probably originates from the binding constants of the ions

Migration of Deformable Vesicles Induced by Ionic Stimuli

We have investigated the dynamics of phospholipid vesicles composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine triggered by ionic stimuli using electrolytes such as CaCl2, NaCl, and NaOH. The ionic stimuli induce two characteristic vesicle dynamics, deformation due to the ion binding to the lipids in the outer leaflet of the vesicle and migration due to the concentration gradient of ions, that is, diffusiophoresis or the interfacial energy gradient mechanism. We examined the deformation pathway for each electrolyte as a function of time and analyzed it based on the surface dissociation model and the area difference elasticity model, which reveals the change of the cross-sectional area of the phospholipid by the ion binding. The metal ions such as Ca2+ and Na+ encourage inward budding deformation by decreasing the cross-sectional area of a lipid, whereas the hydroxide ion (OH–) encourages outward budding deformation by increasing the cross-sectional area of a lipid. When we microinjected these electrolytes toward the vesicles, a strong coupling between the deformation and the migration of the vesicle was observed for CaCl2 and NaOH, whereas for NaCl, the coupling was very weak. This difference probably originates from the binding constants of the ions