Case report and literature review: A thyroid storm patient with severe acute hepatic failure treated by therapeutic plasma exchange and a double plasma molecular absorption system.

Thyroid storm (TS) leading to acute liver failure is rare but fatal in clinical practice and hepatic failure can remarkably limit medication options for TS. We successfully cured a patient with TS complicated with acute hepatic failure using therapeutic plasma exchange (TPE) and a double plasma molecular absorption system (DPMAS) and summarized the case characteristics of 10 similar critical patients reported worldwide. We recommend that patients with TS complicated with liver failure disuse propylthiouracil or methimazole. TPE should be utilized to rapidly decrease thyroid hormone levels, and DPMAS should be considered for supportive treatment in the presence of hepatic encephalopathy or dramatic bilirubin elevations.

Recombinant GM-CSF enhances the bactericidal ability of PMNs by increasing intracellular IL-1ß and improves the prognosis of secondary Pseudomonas aeruginosa pneumonia in sepsis.

This study tested the hypothesis that recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances polymorphonuclear neutrophils (PMNs) via interleukin (IL)-1ß to improve the prognosis of secondary infection in sepsis. The latter stage of sepsis is prone to induce immunosuppression, resulting in secondary fatal infections. Recombinant GM-CSF has become a way for sepsis-induced immunosuppression due to its immunomodulatory effect. However, the functional impact of GM-CSF on PMNs in sepsis remains obscure. This study aimed to study the role of recombinant GM-CSF on the bactericidal ability of PMNs in septic mice, assessing its effect on the prognosis of secondary pneumonia, and explore the mechanism of recombinant GM-CSF by intervening PMNs in patients with sepsis. The C57BL/6J sepsis mouse model was induced by cecal ligation and puncture. Recombinant murine GM-CSF (rmGM-CSF) was used in vivo when mice developed immunosuppression, which was characterized by abnormal bactericidal function of PMNs in peripheral blood. rmGM-CSF improved the prognosis of secondary pneumonia and reversed the function of PMNs. PMNs isolated by Percoll from septic patients were treated by recombinant human GM-CSF (rhGM-CSF) in vitro. The expression of CD11b, reactive oxygen species, phagocytosis, and neutrophil extracellular trap release in PMNs were enhanced by rhGM-CSF treatments. Whole-transcriptomic sequencing of mouse PMNs indicated that recombinant GM-CSF increased the expression of Il1b gene in PMNs. Blocking and inhibiting IL-1ß release effectively counteracted the enhancing effect of GM-CSF on the bactericidal function of PMNs. rmGM-CSF enhances the bactericidal function of PMNs in vivo and improves the prognosis of secondary pneumonia in septic mice, and recombinant GM-CSF increases IL-1ß precursor reserves, which, if stimulated, can rapidly enhance the bactericidal capacity of PMNs.

Mechanically-Activated Microcapsules for 'On-Demand' Drug Delivery in Dynamically Loaded Musculoskeletal Tissues.

Delivery of biofactors in a precise and controlled fashion remains a clinical challenge. Stimuli-responsive delivery systems can facilitate 'on-demand' release of therapeutics in response to a variety of physiologic triggering mechanisms (e.g. pH, temperature). However, few systems to date have taken advantage of mechanical inputs from the microenvironment to initiate drug release. Here, we developed mechanically-activated microcapsules (MAMCs) that are designed to deliver therapeutics in an on-demand fashion in response to the mechanically loaded environment of regenerating musculoskeletal tissues, with the ultimate goal of furthering tissue repair. To establish a suite of microcapsules with different thresholds for mechano-activation, we first manipulated MAMC physical dimensions and composition, and evaluated their mechano-response under both direct 2D compression and in 3D matrices mimicking the extracellular matrix properties and dynamic loading environment of regenerating tissue. To demonstrate the feasibility of this delivery system, we used an engineered cartilage model to test the efficacy of mechanically-instigated release of TGF-ß3 on the chondrogenesis of mesenchymal stem cells. These data establish a novel platform by which to tune the release of therapeutics and/or regenerative factors based on the physiologic dynamic mechanical loading environment, and will find widespread application in the repair and regeneration of numerous musculoskeletal tissues.

Curvature-Driven Migration of Colloids on Tense Lipid Bilayers.

Inspired by proteins that generate membrane curvature, sense the underlying membrane geometry, and migrate driven by curvature gradients, we explore the question: Can colloids, adhered to lipid bilayers, also sense and respond to membrane geometry? We report the migration of Janus microparticles adhered to giant unilamellar vesicles elongated to present spatially varying curvatures. In our experiments, colloids migrate only when the membranes are tense, suggesting that they migrate to minimize membrane area. By determining the energy dissipated along a trajectory, the energy field is inferred to depend on the local deviatoric curvature, like curvature driven capillary migration on interfaces between immiscible fluids. In this latter system, energy gradients are larger, so colloids move deterministically, whereas the paths traced by colloids on vesicles have significant fluctuations. By addressing the role of Brownian motion, we show that the observed migration is analogous to curvature driven capillary migration, with membrane tension playing the role of interfacial tension. Since this motion is mediated by membrane shape, it can be turned on and off by dynamically deforming the vesicle. While particle-particle interactions on lipid membranes have been considered in many contributions, we report here an exciting and previously unexplored modality to actively direct the migration of colloids to desired locations on lipid bilayers.

Liquid crystal Janus emulsion droplets: preparation, tumbling, and swimming.

This study introduces liquid crystal (LC) Janus droplets. We describe a process for the preparation of these droplets, which consist of nematic LC and polymer compartments. The process employs solvent-induced phase separation in emulsion droplets generated by microfluidics. The droplet morphology was systematically investigated and demonstrated to be sensitive to the surfactant concentration in the background phase, the compartment volume ratio, and the possible coalescence of multiple Janus droplets. Interestingly, the combination of a polymer and an anisotropic LC introduces new functionalities into Janus droplets, and these properties lead to unusual dynamical behaviors. The different densities and solubilities of the two compartments produce gravity-induced alignment, tumbling, and directional self-propelled motion of Janus droplets. LC Janus droplets with remarkable optical properties and dynamical behaviors thus offer new avenues for applications of Janus colloids and active soft matter.

Angle- and strain-independent coloured free-standing films incorporating non-spherical colloidal photonic crystals.

Colloidal photonic crystals (CPCs) provide a convenient way to generate structural colour with high stability against degradation under environmental factors. For a number of applications including flexible electronic and energy devices, it is important to generate flexible structural colour that maintains its colour regardless of the angle of observation and the extent of mechanical deformation. However, it is challenging to simultaneously achieve these goals because anisotropy in typical CPC structures (e.g., CPC films) tends to lead to angle-dependent photonic properties and also changes in the lattice constant due to mechanical deformation lead to changes in the photonic properties of CPCs. To overcome these challenges, we present a means of fabricating large-area free-standing films of CPC structures that exhibit angle- and strain-independent photonic characteristics. First, monodisperse double emulsions encapsulating colloidal crystal arrays are prepared using a microfluidic device. By inducing crystallization of highly charged polystyrene particles in the core of double emulsions using osmotic annealing, we generate angle independent colloidal photonic crystal (CPC) supraparticles. Moreover, the shape and crystallinity of the CPC supraparticles can be tuned by changing the concentration of salt in the solution used for osmotic annealing. Subsequently, an array of CPC supraparticles is embedded inside an elastomeric matrix to form a flexible free-standing film, which exhibits structural colours that are independent of viewing angles and externally applied strain.

One-step encapsulation and triggered release based on Janus particle-stabilized multiple emulsions.

One-step formation of stable multiple emulsions is demonstrated using stimuli-responsive amphiphilic Janus particles as emulsifiers. Multiple emulsions stabilized by these stimuli-responsive Janus particles can be induced to release the encapsulant by simply increasing the pH of the continuous phase.

Shape-changing and amphiphilicity-reversing Janus particles with pH-responsive surfactant properties.

Janus particles are biphasic colloids that have two sides with distinct chemistry and wettability. Because of their amphiphilicity, Janus particles present a unique opportunity for stabilizing multiphasic fluid mixtures such as emulsions. Our work is motivated by one class of molecular amphiphiles that change their surfactant properties in response to environmental stimuli. Depending on the environmental conditions, these stimuli-responsive molecular amphiphiles are able to assemble into different structures, generate emulsions with different morphologies, and also induce phase inversion emulsification. We present a new synthesis method utilizing a combination of polymerization-induced phase separation and seeded emulsion polymerization, which allows for the bulk synthesis of highly uniform pH-responsive Janus particles that are able to completely reverse their surfactant properties in response to solution pH. One side of these Janus particles is rich in a hydrophobic monomer, styrene, whereas the other side is rich in a pH-sensitive hydrophilic repeating unit, acrylic acid. These Janus particles change their aggregation/dispersion behavior and also transform into different shapes in response to pH changes. Furthermore, we demonstrate that these Janus particles can stabilize different types of emulsions (oil-in-water and water-in-oil) and, more importantly, induce phase inversion of emulsions in response to changes in solution pH. The pH-responsive aggregation/dispersion behavior of these Janus particles also allows us to tune the interactions between oil-in-water emulsion droplets without inducing destabilization; that is, emulsion drops with attractive or repulsive interactions can be generated by changing the pH of the aqueous phase. Our study presents a new class of colloidal materials that will further widen the functionality and properties of Janus particles as dynamically tunable solid surfactants.

Thermodynamically stable emulsions using Janus dumbbells as colloid surfactants.

One of the most important properties of emulsions is their stability. Most emulsions stabilized with molecular surfactants tend to lose their stability over time via different mechanisms. Although the stability of emulsions stabilized with homogeneous particles have been shown to be superior to that of surfactant-stabilized emulsions, these Pickering emulsions nevertheless are only kinetically stable and thus can undergo destabilization. Janus particles that have two opposite wetting surfaces have shown promise in imparting emulsions with long-term stability because of their strong attachment to the oil-water interface. In this theoretical study, we consider thermodynamics of emulsion stabilization using amphiphilic Janus dumbbells, which are nonspherical particles made of two partially fused spherical particles of opposite wettability. These amphiphilic dumbbells are attractive candidates as colloid surfactants for emulsion stabilization because highly uniform Janus dumbbells can be synthesized in large quantities; thus, their application in emulsion stabilization can become practical. Our theoretical calculation demonstrates that Janus dumbbells can indeed generate thermodynamically stable Pickering emulsions. In addition, we also find that there exists a total oil-water interfacial area that results in the lowest energy state in the system, which occurs when Janus dumbbells available in the system are completely consumed to fully cover the droplet interfaces. We show that the geometry of dumbbells as well as the composition of the emulsion mixtures has significant influences on the average size of dumbbell-stabilized emulsions. We also investigate the effect of asymmetry of Janus dumbbells on the average droplet radius. Our results clearly show that amphiphilic Janus dumbbells provide unique opportunities in stabilizing emulsions for various applications.

Controlling the stability and size of double-emulsion-templated poly(lactic-co-glycolic) acid microcapsules.

The stability and size of poly(lactic-co-glycolic)acid (PLGA)-containing double emulsions and the resulting PLGA microcapsules are controlled by varying the composition of highly monodisperse water-in-oil-in-water (W/O/W) double emulsions. We propose that the basic inner phase of W/O/W double emulsions catalyzes the hydrolysis of PLGA and the ionization of carboxylic acid end groups, which enhances the surface activity of PLGA and facilitates the stabilization of the double emulsions. The size of PLGA-containing double emulsions and that of resulting microcapsules can be readily tuned by osmotic annealing, which depends on the concentration ratio of a solute in the inner and outer phases of double emulsions. The internal volume of PLGA microcapsules can be changed by more than 3 orders of magnitude using this method. This approach also overcomes the difficulty in generating monodisperse double emulsions and microcapsules over a wide range of dimensions using a single microfluidic device. The osmotic annealing method can also be used to concentrate encapsulated species such as colloidal suspensions and biomacromolecules.