Spherulite formation in green nonaqueous media: The impact of urea on gelation in glycerol.

HYPOTHESIS: Large macroscopic assemblies formed by a surfactant, sodium dodecylsulfate (SDS), and glycerol, can be directed to assemble in a hierarchical manner by the addition of a strong hydrogen-bond donor/acceptor, such as urea. CONTEXT: Self-assembly in complex media is important to a range of applications, for instance in biological media, which are multi-component, to industrial formulations, where additives are present for flavour, texture, and preservation. Here, the gelation and self-assembly of sodium dodecylsulfate (SDS) in glycerol is explored in the presence of an additive, urea. Urea was chosen due to its importance both fundamentally and industrially, but also because of its ability to form strong H-bonds and interact with both glycerol and SDS. EXPERIMENTAL: To cover the variety of length scales present in the gel-like phase, a combination of optical microscopy and small-angle X-ray scattering techniques were used to probe the micro- to nanoscale. FINDINGS: On the microscale, the formation of a spectacular spherulite phase, even at low urea contents - 0.1 wt%, upon cooling was observed, a stark difference to the microfibrillar phase observed in the absence of urea. Interestingly, the nanostructure of the two crystalline phases were similar and showed negligible differences. This suggests that urea is not involved in the SDS/glycerol microfibril formation but instead directs the assembly of spherulites by bundling the microfibrils. These ternary systems are also probed as a function of urea content, SDS concentration, and temperature. The observations in this work highlight the importance of small molecules in the self-assembly process, which is relevant both fundamentally but also industrially, where small molecules are often added to formulations.

Ferritin at different iron loading: From biological to nanotechnological applications.

The characterization of the structure of ferritin in solution and the arrangement of iron stored in its cavity are intriguing subjects for both cell biology and applied science, since the protein structure, stability, and easiness of production make it an ideal tool for biomedical applications. We characterized the ferritin structure over a wide range of iron loadings by visible light, X-ray, and neutron scattering techniques. We found that the arrangement of iron ions inside the protein cage resulted in a more disposable arrangement at lower loading factors and then in a crystalline structure. At very high iron content the inner core is composed of magnetite more than ferrihydrite, and the shell of the protein is elastically deformed by the iron crystal growth in an ellipsoidal arrangement. The application of an external radiofrequency (RF) magnetic field affected ferritins at low iron loading factors. Notably the RF modified the iron disposition towards a more dispersed arrangement. The structural characterization of the ferritin at different LFs and in presence of magnetic fields provides useful insights into their physiological behaviour and can help in the design and fine-tuning of ferritin-based nanosystems for biotechnological applications.

Unusual Structural Insights Revealed by Rheo-SAXS Studies of Nonaqueous Crystalline Gels.

Glycerol is a nonaqueous polar solvent and is of interest in many industrial areas due to its beneficial properties, such as green production and biocompatibility. Our previous works have shown the presence of a fibrillar phase on the microscale that consists of lamellar sodium dodecyl sulfate (SDS) crystals containing interstitial glycerol on the nanoscale. The phase is gel-like at room temperature and demonstrates shear-thinning behavior upon application of a shear. Initially, small-angle X-ray scattering coupled with rheology (rheo-SAXS) measurements were performed to elucidate the structural transition of the gel phase under an applied shear, but it became clear that the aging process of the gel has a profound impact on both the gel nanostructure and also the mechanical properties. For younger gels, both the dissolution of SDS crystallites and the alignment of the fibrillar phase were seen. However, in the aged gels, an unexpected foam was formed at shear rates γ˙ > 700 s-1. The microscopic structure of the foam phase was imaged using polarizing light microscopy and brightfield and darkfield optical microscopy. The nanostructure of the foam phase was investigated using rheo-SAXS. The foam phase was shown to be stabilized by the presence of SDS crystallites at the air-liquid interface, and the stability of the foam is high with foam persisting even t = 3 months after formation. These results highlight the importance of investigating green nonaqueous media and the gel aging process, both of which are interesting not only on a fundamental level but also for a range of industrial applications, from personal care products and cosmetics to food science.

Effects of Erucamide on Fiber "Softness": Linking Single-Fiber Crystal Structure and Mechanical Properties.

Erucamide is known to play a critical role in modifying polymer fiber surface chemistry and morphology. However, its effects on fiber crystallinity and mechanical properties remain to be understood. Here, synchrotron nanofocused X-ray Diffraction (nXRD) revealed a bimodal orientation of the constituent polymer chains aligned along the fiber axis and cross-section, respectively. Erucamide promoted crystallinity in the fiber, leading to larger and more numerous lamellae crystallites. The nXRD nanostructual characterization is complemented by single-fiber uniaxial tensile tests, which showed that erucamide significantly affected fiber mechanical properties, decreasing fiber tensile strength and stiffness but enhancing fiber toughness, fracture strain, and ductility. To correlate these single-fiber nXRD and mechanical test results, we propose that erucamide mediated slip at the interfaces between crystallites and amorphous domains during stress-induced single-fiber crystallization, also decreasing the stress arising from the shear displacement of microfibrils and deformation of the macromolecular network. Linking the single-fiber crystal structure with the single-fiber mechanical properties, these findings provide the direct evidence on a single-fiber level for the role of erucamide in enhancing fiber "softness".

A dilute nematic gel produced by intramicellar segregation of two polyoxyethylene alkyl ether carboxylic acids.

MOTIVATION: Surfactants like C8E8CH2COOH have such bulky headgroups that they cannot show the common sphere-to-cylinder transition, while surfactants like C18:1E2CH2COOH are mimicking lipids and form only bilayers. Mixing these two types of surfactants allows one to investigate the competition between intramicellar segregation leading to disc-like bicelles and the temperature dependent curvature constraints imposed by the mismatch between heads and tails. EXPERIMENTS: We establish phase diagrams as a function of temperature, surfactant mole ratio, and active matter content. We locate the isotropic liquid-isotropic liquid phase separation common to all nonionic surfactant systems, as well as nematic and lamellar phases. The stability and rheology of the nematic phase is investigated. Texture determination by polarizing microscopy allows us to distinguish between the different phases. Finally, SANS and SAXS give intermicellar distances as well as micellar sizes and shapes present for different compositions in the phase diagrams. FINDINGS: In a defined mole ratio between the two components, intramicellar segregation wins and a viscoelastic discotic nematic phase is present at low temperature. Partial intramicellar mixing upon heating leads to disc growth and eventually to a pseudo-lamellar phase. Further heating leads to complete random mixing and an isotropic phase, showing the common liquid-liquid miscibility gap. This uncommon phase sequence, bicelles, lamellar phase, micelles, and water-poor packed micelles, is due to temperature induced mixing combined with dehydration of the headgroups. This general molecular mechanism explains also why a metastable water-poor lamellar phase quenched by cooling can be easily and reproducibly transformed into a nematic phase by gentle hand shaking at room temperature, as well as the entrapment of air bubbles of any size without encapsulation by bilayers or polymers.

Sterically Enhanced Control of Enzyme-Assisted DNA Assembly.

Traditional methods for the assembly of functionalised DNA structures, involving enzyme restriction and modification, present difficulties when working with small DNA fragments (<100 bp), in part due to a lack of control over enzymatic action during the DNA modification process. This limits the design flexibility and range of accessible DNA structures. Here, we show that these limitations can be overcome by introducing chemical modifications into the DNA that spatially restrict enzymatic activity. This approach, sterically controlled nuclease enhanced (SCoNE) DNA assembly, thereby circumvents the size limitations of conventional Gibson assembly (GA) and allows the preparation of well-defined, functionalised DNA structures with multiple probes for specific analytes, such as IL-6, procalcitonin (PCT), and a biotin reporter group. Notably, when using the same starting materials, conventional GA under typical conditions fails. We demonstrate successful analyte capture based on standard and modified sandwich ELISA and also show how the inclusion of biotin probes provides additional functionality for product isolation.

Real-Time pH-Dependent Self-Assembly of Ionisable Lipids from COVID-19 Vaccines and In Situ Nucleic Acid Complexation.

Ionisable amino-lipid is a key component in lipid nanoparticles (LNPs), which plays a crucial role in the encapsulation of RNA molecules, allowing efficient cellular uptake and then releasing RNA from acidic endosomes. Herein, we present direct evidence for the remarkable structural transitions, with decreasing membrane curvature, including from inverse micellar, to inverse hexagonal, to two distinct inverse bicontinuous cubic, and finally to a lamellar phase for the two mainstream COVID-19 vaccine ionisable ALC-0315 and SM-102 lipids, occurring upon gradual acidification as encountered in endosomes. The millisecond kinetic growth of the inverse cubic and hexagonal structures and the evolution of the ordered structural formation upon ionisable lipid-RNA/DNA complexation are quantitatively revealed by in situ synchrotron radiation time-resolved small angle X-ray scattering coupled with rapid flow mixing. We found that the final self-assembled structural identity, and the formation kinetics, were controlled by the ionisable lipid molecular structure, acidic bulk environment, lipid compositions, and nucleic acid molecular structure/size. The implicated link between the inverse membrane curvature of LNP and LNP endosomal escape helps future optimisation of ionisable lipids and LNP engineering for RNA and gene delivery.

Evaluating the use of the respiratory-rate oxygenation index as a predictor of high-flow nasal cannula oxygen failure in COVID-19.

BACKGROUND: It can be challenging for clinicians to predict which patients with respiratory failure secondary to coronavirus disease 2019 (COVID-19) will fail on high-flow nasal cannula (HFNC) oxygen and require escalation of therapy. This study set out to evaluate the association between the respiratory rate-oxygenation index (ROX) and HFNC failure in such patients and to assess whether ROX trajectory correlates with treatment failure. METHODS: This was a single-centre, retrospective, observational study of patients with COVID-19 requiring HFNC, conducted over a 3-month period. ROX was calculated as "pulse-oximetry oxygen saturation (SpO2) over the fractional inspired oxygen concentration (FiO2)/respiratory rate" for each patient at 2, 4, and 12 hours from starting HFNC. HFNC failure was defined as escalation to continuous positive airway pressure ventilation or invasive mechanical ventilation (IMV). Time-to-event analyses were performed to account for the longitudinal data set and time-dependent variables. RESULTS: We included 146 patients. Ninety-three (63.7%) experienced HFNC failure, with 53 (36.3%) requiring IMV. Higher ROX values were associated with a lower subhazard of HFNC failure on time-to-HFNC failure analysis (subhazard ratio, 0.29; 95% confidence interval [CI], 0.18-0.46; P<0.001). This remained true after controlling for informative censoring. Median ROX values changed differentially over time, increasing in the HFNC success group (0.06 per hour; 95% CI, 0.05-0.08; P<0.001) but not in the HFNC failure group (0.004 per hour; 95% CI, -0.05 to 0.08; P=0.890). CONCLUSIONS: A higher ROX is associated with a lower risk of HFNC failure. Monitoring ROX trajectory over time may help identify patients at risk of treatment failure. This has potential clinical applications; however, future prospective studies are required.

Novel Approaches for the Application of Herbs for Skin Care.

Skin is the largest non-parenchymal organ of the human body. It constitutes a natural barrier against pathogens and harmful environmental exposures and contributes to the human body's homeostasis. Conditions affecting the skin range from infections and injury to autoimmune diseases and cancer. Herbs have been used to treat dermatological conditions for a long time. Traditional approaches to delivering herbs to the skin include ointments, gels, creams, and lotions. However, poor lipophilicity or hydrophilicity in most herbal preparations results in limited bioavailability and poor penetration, restricting their effectiveness. Nanotechnology-based approaches have major potential, showing more promising results in enhancing transdermal penetration than traditional approaches. This review article summarizes such advances and sheds light on future directions in using nanotechnology-based strategies.

The effect of ethanol on fibrillar hydrogels formed by glycyrrhizic acid monoammonium salt.

MOTIVATION: The monoammonium salt of glycyrrhizic acid (AGA) is known to form fibrillar hydrogels and few studies regarding self-assembly of AGA have been published. Yet, the understanding of the fibrillar microstructures and the gelation remains vague. Thus, we attempt to achieve a deeper understanding of the microstructures and the gelation process of binary solutions of AGA in water. Further, we examine the effect of ethanol on the microstructures to pave the way for potential enhancement of drug loading in AGA hydrogels. EXPERIMENTS: A partial room temperature phase map of the ternary system AGA/ethanol/water was recorded. Small-angle X-ray and neutron scattering experiments were performed over wide ranges of compositions in both binary AGA/water and ternary AGA/ethanol/water mixtures to get access to the micro-structuring. FINDINGS: Binary aqueous solutions of AGA form birefringent gels consisting of a network of long helical fibrils. 'Infinitely' long negatively charged fibrils are in equilibrium with shorter fibrils (≈25 nm), both of which have a diameter of about 3 nm and are made of around 30 stacks of AGA per helical period (≈9nm), with each stack consisting of two AGA molecules. The interaxial distance (order of magnitude ≈20 nm) varies with an almost two-dimensional swelling law. Addition of ethanol reduces electrostatic repulsion and favors the formation of fibrillar end caps, reducing the average length of shorter fibrils, as well as the formation of small, swollen aggregates. While the gel network built by the long fibrils is resilient to a significant amount of ethanol, all fibrils are finally dissolved into small aggregates above a certain threshold concentration of ethanol (≈30 wt%).

Correction: Interpenetration of fractal clusters drives elasticity in colloidal gels formed upon flow cessation.

Correction for 'Interpenetration of fractal clusters drives elasticity in colloidal gels formed upon flow cessation' by Noémie Dagès et al., Soft Matter, 2022, 18, 6645-6659, https://doi.org/10.1039/D2SM00481J.

Atypical presentation of Lemierre syndrome in a young healthy man with acute jaundice.

This report presents a case of Lemierre syndrome caused by Fusobacterium necrophorum in a healthy young adult who presented atypically with shortness of breath and jaundice but no clinical or diagnostic evidence of thrombophlebitis. Due to this unusual presentation with jaundice, diagnosis was challenging and delayed. However, the patient was successfully initiated on a prolonged course of intravenous antibiotics; he required a period in the intensive care unit and was discharged without significant complications. This report aims to raise awareness of the diagnosis and treatment of this rare condition and to highlight both common and unusual presentations of the syndrome.

Increased rate of listening difficulties in autistic children.

INTRODUCTION: Auditory challenges are both common and disruptive for autistic children and evidence suggests that listening difficulties may be linked to academic underachievement (Ashburner, Ziviani & Rodger, 2008). Such deficits may also contribute to issues with attention, behavior, and communication (Ashburner et al., 2008; Riccio, Cohen, Garrison & Smith, 2005). The present study aims to summarize the auditory challenges of autistic children with normal pure-tone hearing thresholds, and perceived listening difficulties, seen at auditory-ASD clinics in the US and Australia. METHODS: Data were compiled on a comprehensive, auditory-focused test battery in a large clinical sample of school-age autistic children with normal pure-tone hearing to date (N = 71, 6-14 years). Measures included a parent-reported auditory sensory processing questionnaire and tests of speech recognition in noise, binaural integration, attention, auditory memory and listening comprehension. Individual test performance was compared to normative data from children with no listening difficulties. RESULTS: Over 40% of patients exhibited significantly reduced speech recognition in noise and abnormal dichotic integration that were not attributed to deficits in attention. The majority of patients (86%) performed abnormally on at least one auditory measure, suggesting that functional auditory issues can exist in autistic patients despite normal pure-tone sensitivity. CONCLUSION: Including functional listening measures during audiological evaluations may improve clinicians' ability to detect and manage the auditory challenges impacting this population. Learner Outcomes: 1) Readers will be able to describe the auditory difficulties experienced by some autistic patients (ASD). 2) Readers will be able to describe clinical measures potentially useful for detecting listening difficulties in high-functioning autistic children.

Interpenetration of fractal clusters drives elasticity in colloidal gels formed upon flow cessation.

Colloidal gels are out-of-equilibrium soft solids composed of attractive Brownian particles that form a space-spanning network at low volume fractions. The elastic properties of these systems result from the network microstructure, which is very sensitive to shear history. Here, we take advantage of such sensitivity to tune the viscoelastic properties of a colloidal gel made of carbon black nanoparticles. Starting from a fluidized state at an applied shear rate 0, we use an abrupt flow cessation to trigger a liquid-to-solid transition. We observe that the resulting gel is all the more elastic when the shear rate 0 is low and that the viscoelastic spectra can be mapped on a master curve. Moreover, coupling rheometry to small angle X-ray scattering allows us to show that the gel microstructure is different from gels solely formed by thermal agitation where only two length scales are observed: the dimension of the colloidal and the dimension of the fractal aggregates. Competition between shear and thermal energy leads to gels with three characteristic length scales. Such gels structure in a percolated network of fractal clusters that interpenetrate each other. Experiments on gels prepared with various shear histories reveal that cluster interpenetration increases with decreasing values of the shear rate 0 applied before flow cessation. These observations strongly suggest that cluster interpenetration drives the gel elasticity, which we confirm using a structural model. Our results, which are in stark contrast to previous literature, where gel elasticity was either linked to cluster connectivity or to bending modes, highlight a novel local parameter controlling the macroscopic viscoelastic properties of colloidal gels.

High-resolution structural elucidation of extremely swollen lyotropic phases.

Self-assembled lyotropic phases are important in a variety of applications, in particular microemulsions are essential for formulation science. A spectacular situation arises when microemulsions are made to swell by systematically increasing the bending modulus of the surfactant film separating the oil and water regions. In an attempt to realize such extremely swollen microemulsion phases, Peter et al. [Phys. Rev. Lett., 76 (1996) 3866] found a variety of lyotropic phases including a long-range ordered three-dimensional cubic phase over a narrow section of the complex phase diagram of a pseudo-quaternary system composed of decane, brine, octanol, and sodium dodecyl sulfate. In this work, the same region of the phase diagram was reinvestigated using high-resolution small-angle X-ray scattering (HR-SAXS) and rheo-SAXS, which is an important technical aspect for homogenizing the sample and orienting the structural units. Whilst the formation of a swollen two-dimensional hexagonal phase was observed, the structural features of a cubic phase were not detected. The long correlation lengths noted prior were also seen here, over 2000 nm for the hexagonal phase, taken from rheo-SAXS measurements. Based on the measurements covering more than three orders of magnitude in scattering vector, the structure appeared to be an organization of elongated swollen emulsion droplets, which could form an interconnected structure, dense liquid-like order, or further order into a hexagonal morphology with unusually large lattice spacings for a surfactant system.

Fracto-eutectogels: SDS fractal dendrites via counterion condensation in a deep eutectic solvent.

Glyceline, a deep eutectic solvent comprising glycerol and choline chloride, is a green nonaqueous solvent with potential industrial applications. Molecular mechanisms of surfactant self-assembly in deep eutectic solvents are expected to differ from those in their constituent polar components and are not well understood. Here we report the observation of self-assembled SDS fractal dendrites with dimensions up to ∼mm in glyceline at SDS concentrations as low as cSDS ∼ 0.1 wt%. The prevalence of these dendritic fractal aggregates led to the formation of a gel phase at SDS concentrations above ≥1.9 wt% (the critical gelation concentration cCGC). The gel microscopic structure was visualised using polarised light microscopy (PLM); rheology measurements confirmed the formation of a colloidal gel, where the first normal stress difference was negative and the elastic modulus was dominant. Detailed nano-structural characterisation by small-angle neutron scattering (SANS) further confirmed the presence of fractal aggregates. Such SDS aggregation or gelation has not been observed in water at such low surfactant concentrations, whereas SDS has been reported to form lamellar aggregates in glycerol (a component of glyceline). We attribute the formation of the SDS fractal dendrites to the condensation of counterions (i.e. the choline ions) around the SDS aggregates - a diffusion-controlled process, leading to the aggregate morphology observed. These unprecedented results shed light on the molecular mechanisms of surfactant self-assembly in deep eutectic solvents, important to their application in industrial formulation.

Circulating miRNAs as early indicators of diet and physical activity response in women with metastatic breast cancer.

Treatments for metastatic breast cancer (MBC) improve survival but often impose prolonged symptom burden. We performed molecular characterization of 84 miRNAs in the circulating serum of women with MBC to explore possible early indicators of intervention response. Expression levels of miR-10a-5p and miR-211-5p were downregulated in nonresponders, but upregulated in responders (miR-10a-5p: 0.40-fold and eightfold; miR 211-5p: 0.47-fold and fourfold). miR-205-5p expression was upregulated in both nonresponders and responders, but to a greater extent in responders (1.8-fold and sixfold). Additionally, levels of miR-10a-5p were negatively correlated with expression levels of IL-6 (r = -0.412). Exploration of these pathways may reveal mechanisms of action in lifestyle interventions aimed at improving quality of life and impacting disease progression for women with MBC.

Biobased Carbon Dots: From Fish Scales to Photocatalysis.

The synthesis, characterization and photoreduction ability of a new class of carbon dots made from fish scales is here described. Fish scales are a waste material that contains mainly chitin, one of the most abundant natural biopolymers, and collagen. These components make the scales rich, not only in carbon, hydrogen and oxygen, but also in nitrogen. These self-nitrogen-doped carbonaceous nanostructured photocatalyst were synthesized from fish scales by a hydrothermal method in the absence of any other reagents. The morphology, structure and optical properties of these materials were investigated. Their photocatalytic activity was compared with the one of conventional nitrogen-doped carbon dots made from citric acid and diethylenetriamine in the photoreduction reaction of methyl viologen.

Every Day Counts: a randomized pilot lifestyle intervention for women with metastatic breast cancer.

PURPOSE: To explore the feasibility, adherence, safety and potential efficacy of Every Day Counts; a randomized pilot trial designed for women with metastatic breast cancer (MBC) framed by the American Cancer Society nutrition and physical activity (PA) guidelines METHODS: Women with clinically stable MBC were recruited to complete an interview, dual energy X-ray absorptiometry imaging and phlebotomy at baseline and post-intervention. Multidimensional quality of life, symptom burden, lifestyle behaviors (nutrition and PA) and biomarkers of prognosis were procured and quantified. Women were randomized to the immediate intervention or a waitlist control arm. The 12-week intervention included a curriculum binder, lifestyle coaching (in-person and telephone-based sessions) and intervention support (activity monitor, text messaging, cooking classes.) Women in the waitlist control were provided monthly text messaging. RESULTS: Forty women were recruited within 9 months (feasibility). Women in the immediate intervention attended 86% of all 12 weekly coaching sessions (adherence) and showed significant improvements in general QOL (p = 0.001), and QOL related to breast cancer (p = 0.001), endocrine symptoms (p = 0.002) and fatigue (p = 0.037), whereas the waitlist control did not (all p values ≥ 0.05) (efficacy). PA significantly increased for women in the intervention compared to control (p < 0.0001), while dietary changes were less evident across groups due to high baseline adherence. No significant changes in biomarkers or lean mass were noted, yet visceral adipose tissue declined (p = 0.001). No intervention-related injuries were reported (safety). Qualitative feedback strongly supports the desire for a longer intervention with additional support. CONCLUSIONS: Lifestyle interventions are of interest, safe and potentially beneficial for women with MBC. A larger trial is warranted.

Future Interventional Radiologists and Where to Find Them-Insights from Five UK Interventional Radiology Symposia for Junior Doctors and Medical Students.

BACKGROUND: The interventional radiology (IR) trainee recruitment in the UK is lagging behind the pace of service expansion and is potentially hindered by underrepresented undergraduate curricula. Understanding the contributing factors that encourage junior doctors and medical students to consider an IR career will help the IR community to better focus the efforts on recruiting and nurturing the next generation. METHODS: Anonymised questionnaires on undergraduate and postgraduate IR exposure were distributed to attendees of five UK IR symposia between 2019 and 2020. RESULTS: 220 responses were received from 103 (47%) junior doctors and 117 (53%) medical students. Prior IR exposure strongly correlates with individuals' positive views towards an IR career (Pearson's R = 0.40, p < 0.001), with involvement in clinical activities as the most important independent contributor (OR 3.6, 95%CI 1.21-10.50, p = 0.021). Longer time spent in IR (especially as elective modules) and IR-related portfolio-building experiences (such as participating in research, attending conferences and obtaining career guidance) demonstrate strong association with willingness to pursue an IR career for the more motivated (p values < 0.05). The symposia had overall positive effects on subjective likelihood to pursue an IR career, particularly among junior doctors who face near-term career choices (p < 0.001). CONCLUSION: Our study, focusing on a self-selected cohort, identified contributing factors to individuals' willingness to pursue an IR career. Symposia have additional recruitment effects in extra-curricular settings. Active engagement with junior doctors and medical students through clinical activities and non-clinical portfolio-related experiences are key to generate informed and motivated candidates for the future of IR.