Facile In Situ Assembly of Nanofibers within Three-Dimensional Porous Matrices with Arbitrary Characteristics for Creating Biomimetic Architectures.

It is challenging to recapitulate the natural extracellular matrix's hierarchical nano/microfibrous three-dimensional (3D) structure with multilevel pores, good mechanical and hydrophilic properties, and excellent bioactivity for designing and developing advanced biomimetic materials. This work reports a new facile strategy for the scalable manufacturing of such a 3D architecture. Natural polymers in an aqueous solution are interpenetrated into a 3D microfibrous matrix with arbitrary shapes and property characteristics to self-assemble in situ into a nanofibrous network. The collagen fiber-like hierarchical structure and interconnected multilevel pores are achieved by self-assembly of the formed nanofibers within the 3D matrix, triggered by a simple cross-linking treatment. The as-prepared alginate/polypropylene biomimetic matrices are bioactive and have a tunable mechanical property (compressive modulus from ∼17 to ∼24 kPa) and a tunable hydrophilicity (water contact angle from ∼94° to 63°). This facile and versatile strategy allows eco-friendly and scalable manufacturing of diverse biomimetic matrices or modification of any existing porous matrices using different polymers.

Silk Hydrogel Electrostatically Functionalized with a Polycationic Antimicrobial Peptide: Molecular Interactions, Gel Properties, and Antimicrobial Activity.

Functionalization of silk fibroin hydrogel with antimicrobial activity is essential for promoting the applications of this excellent biomaterial. In this work, a simple approach based on electrostatic interaction is adopted to produce antimicrobial silk hydrogel containing an antimicrobial peptide (AMP), polymyxin B, an important last-line antibiotic to treat multidrug-resistant bacterial superbugs. The polycationic property of this peptide and the negative charge of silk fibroin lead to strong interactions between them, as demonstrated by changes in nanofibril structure, gelation kinetics, ζ-potential, fluorescence emission, and rheological properties of the gel. The hydrogels loaded with polymyxin B demonstrated antimicrobial activity against two Gram-negative bacterial strains. A combination of the results from the different characterizations suggests that the optimal molar ratio of polymyxin B to silk fibroin is 1:2.5. As most AMPs are cationic, this electrostatic approach is suitable for the straightforward functionalization of inert silk hydrogel with other AMPs.

Fibrous-Structured Freestanding Electrodes for Oxygen Electrocatalysis.

Electrocatalysts used for oxygen reduction and oxygen evolution reactions are critical materials in many renewable-energy devices, such as rechargeable metal-air batteries, regenerative fuel cells, and water-splitting systems. Compared with conventional electrodes made from catalyst powders, oxygen electrodes with a freestanding architecture are highly desirable because of their binder-free fabrication and effective elimination of catalyst agglomeration. Among all freestanding electrode structures that have been investigated so far, fibrous materials exhibit many unique advantages, such as a wide range of available fibers, low material and material-processing costs, large specific surface area, highly porous structure, and simplicity of fiber functionalization. Recent advances in the use of fibrous structures for freestanding electrocatalytic oxygen electrodes are summarized, including electrospun nanofibers, bacterial cellulose, cellulose fibrous structures, carbon clothes/papers, metal nanowires, and metal meshes. After detailed discussion of common techniques for oxygen electrode evaluation, freestanding electrode fabrication, and their electrocatalytic performance, current challenges and future prospects are also presented for future development.

Molecular dynamics simulations informed by membrane lipidomics reveal the structure-interaction relationship of polymyxins with the lipid A-based outer membrane of Acinetobacter baumannii.

BACKGROUND: MDR bacteria represent an urgent threat to human health globally. Polymyxins are a last-line therapy against life-threatening Gram-negative 'superbugs', including Acinetobacter baumannii. Polymyxins exert antimicrobial activity primarily via permeabilizing the bacterial outer membrane (OM); however, the mechanism of interaction between polymyxins and the OM remains unclear at the atomic level. METHODS: We constructed a lipid A-based OM model of A. baumannii using quantitative membrane lipidomics data and employed all-atom molecular dynamics simulations with umbrella sampling techniques to elucidate the structure-interaction relationship and thermodynamics governing the penetration of polymyxins [B1 and E1 (i.e. colistin A) representing the two clinically used polymyxins] into the OM. RESULTS: Polymyxin B1 and colistin A bound to the A. baumannii OM by the initial electrostatic interactions between the Dab residues of polymyxins and the phosphates of lipid A, competitively displacing the cations from the headgroup region of the OM. Both polymyxin B1 and colistin A formed a unique folded conformation upon approaching the hydrophobic centre of the OM, consistent with previous experimental observations. Polymyxin penetration induced reorientation of the headgroups of the OM lipids near the penetration site and caused local membrane disorganization, thereby significantly increasing membrane permeability and promoting the subsequent penetration of polymyxin molecules into the OM and periplasmic space. CONCLUSIONS: The thermodynamics governing the penetration of polymyxins through the outer leaflet of the A. baumannii OM were examined and novel structure-interaction relationship information was obtained at the atomic and membrane level. Our findings will facilitate the discovery of novel polymyxins against MDR Gram-negative pathogens.

The key structural features governing the free radicals and catalytic activity of graphite/graphene oxide.

The presence of unpaired electrons (radicals) due to structural defects is believed to contribute to the catalytic reactivity of carbon materials. Graphite oxide and graphene oxide (GO) consist of significant structural defects and hence are considered more reactive than graphite and graphene. However, the relationship between their radical content/reactivity and their physical and chemical structures remains unknown, which limits the fabrication of high efficiency carbon-based catalysts. In this work, we progressively oxidize graphite to achieve graphite oxide and GO with different levels of oxidation and different sizes. It is observed that a maximal radical content can be achieved on graphite oxide with a C/O ratio of ca. 3.0 and a thickness of around 50 nm. Such a graphite oxide contains about 45% of π bonds and 38% of oxygenated bonds, respectively. Thinner or thicker sheets have lower radical contents due to over or insufficient oxidation, respectively. Single GO sheets with high radical contents can only be produced through a combination of oxidation and reduction. The catalytic activity of the graphite/graphene oxide for phenol degradation was found to be linearly correlated to their radical contents. The observations are significant for the advancement of carbon-based metal-free catalysis.

Understanding the epidemiological characteristics of EV71 and CVA16 infection to aid the diagnosis and treatment of hand, foot, and mouth disease.

Hand, foot, and mouth disease (HFMD) have been recognized over the past several years as a highly infectious disease in children. Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the two major causative agents. The objective of this study was to determine the optimal time and method of HFMD detection, explore the seroconversion of IgM and IgG antibodies, and examine the response of neutralizing antibody (NtAb) to EV71 or CVA16. Between January 2016 and December 2017, a total of 460 patients, diagnosed with HFMD based on clinical symptoms and hospitalized in the First Hospital of Jilin University, were recruited for the study. At approximately 72 hours post illness onset, we observed that the positive rate of both IgM and real-time polymerase chain reaction detection of EV71 or CVA16 was the highest, this could be considered as the optimal detection time for clinical diagnosis. During the initial 0 -96 hours, the relative highest IgM and the relative lowest IgG antibody levels were observed. The NtAb titers to EV71 and CVA16 also gradually increased with time, showing a positive correlation with age, and being the predominant factor during the hospitalized days. Thus, our study provides important information for the clinical diagnosis and treatment of HFMD.

A Biomimetic Supramolecular Approach for Charge Transfer between Donor and Acceptor Chromophores with Aggregation-Induced Emission.

Supramolecular assembly of chromophores with inherent resistance to aggregation-induced self-quenching is significant to applications such as chemical sensing and organic light emitting diodes (OLEDs). In this work, molecular gels with aggregation-induced emission (AIE) are constructed by simply coassembling AIE chromophores (electron donor or acceptor) with a nonfluorescent molecular gelator. The binary gels are fluorescent even at very low concentrations of the AIE chromophores, indicating that the rotation of their aromatic cores is restricted in the gel network. In tertiary gels, the fluorescence of the donor chromophore can be efficiently reduced by the acceptor chromophore through a combination of static and dynamic quenching process, via charge transfer from the donor to the acceptor. This work demonstrates a convenient approach to fabricate a supramolecular charge transfer system using an AIE donor and acceptor.

Prevailing genotype distribution and characteristics of human respiratory syncytial virus in northeastern China.

Although human respiratory syncytial virus (RSV) is one of the most common viruses inducing respiratory tract infections in young children and the elderly, the genotype distribution and characteristics of RSV in northeastern China have not been investigated. Here, we identified 25 RSV-A and 8 RSV-B strains from 80 samples of patients with respiratory infections between February 2015 and May 2015. All 25 RSV-A viruses were classified as the ON1 genotype, which rapidly spread and became the dominant genotype in the world since being identified in Ontario (Canada) in December 2010. All eight RSV-B viruses belonged to the BA genotype with a 60-nucleotide duplication, seven of which formed two new genotypes, BA-CCA and BA-CCB. The remaining RSV-B virus clustered with one of the Hangzhou strains belonging to genotype BA11. Construction of a phylogenetic tree and amino acid substitution analysis showed that Changchun ON1 viruses exclusively constituted Lineages 3, 5 and 6, and contained several unique and newly identified amino acid substitutions, including E224G, R244K, L289I, Y297H, and L298P. Selective pressure was also evaluated, and various N and O-glycosylation sites were predicted. This study provides the first genetic analysis of RSV in northeastern China and may facilitate a better understanding of the evolution of this virus locally and globally. J. Med. Virol. 89:222-233, 2017. © 2016 The Authors. Journal of Medical Virology Published by Wiley Periodicals, Inc.

One-pot synthesis of silicon based nanoparticles with incorporated phthalocyanine for long-term bioimaging and photo-dynamic therapy of tumors.

Combining the merits of delivery vectors with drug molecules is one of the key directions for development of efficient cancer monitoring and treatment techniques. In this work, a novel type of silicon based composite nanoparticles (NPs) with incorporated hydrophobic phthalocyanine molecules (Pc) was synthesized via a facile one-pot method. The as-synthesized Pc@Si NPs, with a small size of 4.2 ± 0.8 nm, have excellent dispersibility in water and good biocompatibility with cells, in addition to favorable photoluminescence and robust photostability even in cells. Moreover, the Pc@Si NPs show significant in vitro cancer cell killing and in vivo tumor inhibiting abilities upon near-infrared light exposure, due to the photodynamic therapy (PDT) effect of Pc. This work develops an efficient fluorescent PDT drug carrier; moreover, the facile one-pot synthesis strategy may be used generally to prepare silicon-based composite NPs incorporated with diverse hydrophobic drugs/diagnostic molecules for a wide range of biomedical applications.

Recognition of chiral zwitterionic interactions at nanoscale interfaces by chiroplasmonic nanosensors.

The ability to detect chiral molecules renders plasmonic nanosensors as promising tools for the study of chirality phenomena in living systems. Using gold nanorod based plasmonic nanosensors, we investigated here typically chiral zwitterionic electrostatic (Zw-Es) and hydrogen-bonding (Hb) interactions occurring via amine and carboxylic groups at nanoscale interfaces in aqueous solutions. Our results reveal that the plasmonic circular dichroism responses of the nanosensors can have both conformational sensitivity and chiral selectivity to the interfacial molecular interactions. Such a dual function of the plasmonic nanosensors enables a new chiroptical way to differentiate between chiral Zw-Es and Hb interactions, to monitor the transformation between these two interaction forces, and particularly to recognize homochiral Zw-Es interactions in solution. Together with the surface enhanced Raman scattering (SERS) technique, this plasmonic CD based biosensing could have important values for the insightful understanding of chirality-dependent molecular recognition in biological and pharmaceutical systems.

Reduced graphene oxide directed self-assembly of phospholipid monolayers in liquid and gel phases.

The response of cell membranes to the local physical environment significantly determines many biological processes and the practical applications of biomaterials. A better understanding of the dynamic assembly and environmental response of lipid membranes can help understand these processes and design novel nanomaterials for biomedical applications. The present work demonstrates the directed assembly of lipid monolayers, in both liquid and gel phases, on the surface of a monolayered reduced graphene oxide (rGO). The results from atomic force microscopy indicate that the hydrophobic aromatic plane and the defect holes due to reduction of GO sheets, along with the phase state and planar surface pressure of lipids, corporately determine the morphology and lateral structure of the assembled lipid monolayers. The DOPC molecules, in liquid phase, probably spread over the rGO surface with their tails associating closely with the hydrophobic aromatic plane, and accumulate to form circles of high area surrounding the defect holes on rGO sheets. However, the DPPC molecules, in gel phase, prefer to form a layer of continuous membrane covering the whole rGO sheet including defect holes. The strong association between rGO sheets and lipid tails further influences the melting behavior of lipids. This work reveals a dramatic effect of the local structure and surface property of rGO sheets on the substrate-directed assembly and subsequent phase behavior of the supported lipid membranes.

Synergistic Coassembly of Two Structurally Different Molecular Gelators.

Coassembly of molecules can produce materials with improved properties and functionalities. To this end, achieving a molecular level understanding of the interactions governing the coassembly is essential. In this work, two molecular gelators with significantly different structures and main intermolecular forces for assembly were coassembled. The elastic moduli of the hybrid gels are more than 1 order of magnitude higher than those of the gels formed by the individual gelators, showing an obvious synergistic effect. The interactions between the gelators were investigated with confocal microscopy and both one-dimensional and two-dimensional nuclear magnetic resonance. It was found that the two gelators coassemble to form fibers due to the nonspecific van der Waals interactions between their alkyl chains and the specific interactions between their functional groups. Switching from one gelator-dominated fiber network to the other gelator-dominated fiber network was achieved at a critical molar ratio of the gelators. The two gelators serve as additives of each other to tune the nucleation and growth of the fiber networks. The observations of this work are significant to the development of materials with improved properties by coassembly of different molecules.

Broad protection with an inactivated vaccine against primary-isolated lethal enterovirus 71 infection in newborn mice.

BACKGROUND: Circulating enterovirus 71 (EV-A71)-associated hand, foot, and mouth disease is on the rise in the Asian-Pacific region. Although animal models have been developed using mouse-adapted EV-A71 strains, mouse models using primary EV-A71 isolates are scarce. Lethal animal models with circulating EV-A71 infection would contribute to studies of pathogenesis as well as vaccine development and evaluation. RESULTS: In this study, we established a lethal mouse model using primary EV-A71 isolates from patients infected with serotypes that are currently circulating in humans. We also characterized the dose-dependent virulence and pathologic changes of circulating EV-A71 in this mouse model. Most importantly, we have established this mouse model as a suitable system for EV-A71 vaccine evaluation. An inactivated EV-A71 vaccine candidate offered complete protection from death induced by various circulating EV-A71 viruses to neonatal mice that were born to immunized female mice. The sera of the immunized dams and their pups showed higher neutralization titers against multiple circulating EV-A71 viruses. CONCLUSIONS: Thus, our newly established animal model using primary EV-A71 isolates is helpful for future studies on viral pathogenesis and vaccine and drug development.

The chain conformation and relaxation dynamics of poly(acrylic acid)-graft-poly(ethylene oxide)-graft-dodecyl in water: effect of side-chains and distribution of counterions.

We present a study on the dielectric behavior of an aqueous solution of an amphiphilic copolymer, poly(acrylic acid)-graft-poly(ethylene oxide)-graft-dodecyl (PAA-g-PEO-g-dodecyl), in the frequency range of 40 Hz to 110 MHz at varying concentrations and temperatures. After eliminating the electrode polarization at low-frequency, three dielectric relaxation processes were observed at about 1.2 MHz, 150 kHz and 30 kHz, whose mechanisms were proved to originate from the fluctuations of free counterions, the fluctuation of condensed counterions, and the rotation of intramolecular aggregates, respectively. The concentration dependence of the dielectric increment Δε and relaxation time τ for these three relaxations presents an abrupt change at 0.15 mg ml(-1), indicating that PAA-g-PEO-g-dodecyl molecules undergo a conformational transition from intramolecular aggregates to intermolecular aggregates. Moreover, both Δε and τ show a clear transition at about 317 K, suggesting a partial collapse of the aggregates. The correlation length and the contour length of the PAA-g-PEO-g-dodecyl chain were estimated according to Ito's theory of counterion fluctuation. It was found that the hydrophobic/hydrophilic side-chains affected the microscopic conformation of PAA, and the hydrogen-bond interactions greatly influenced the conformation. Additionally, the activation energy of these three relaxations was calculated and the process of ionic conduction was studied and the results were used to discuss counterion distribution and ion conduction.

Distinct kinetics of molecular gelation in a confined space and its relation to the structure and property of thin gel films.

Thin films of molecular gels formed in a confined space have potential applications in transdermal delivery, artificial skin, molecular electronics, etc. The microstructures and properties of thin gel films can be significantly different from those of their bulk counterparts. However, so far a comprehensive understanding of the effects of spatial confinement on the molecular gelation kinetics, fiber network structure and related mechanical properties is still lacking. In this work, using rheological techniques, we investigated the effect of one-dimensional confinement on the formation kinetics of fiber networks in the molecular gelation process. Fractal analyses of the kinetic information in terms of an extended Dickinson model enabled us to describe quantitatively the distinct kinetic signature of molecular gelation. The structural features derived from gelation kinetics support well the fractal patterns of the fiber networks acquired by optical and electron microscopy. With the kinetics-structure correlation, we can gain an in-depth understanding of the confinement-induced differences in the structure and consequently the mechanical properties of a model molecular gelling system. Particularly, the confinement induced structural transition, from a three-dimensional, dense and compact spherulitic network composed of highly branched fibers to a quasi-two-dimensional sparse spherulitic network composed of less branched fibers and entangled fibrils at the boundary areas, renders a gel film to become less stiff but more ductile. Our study suggests here a new strategy of engineering the fiber network microstructure to achieve functional gel films with unusual but useful properties.

Vesicle deposition and subsequent membrane-melittin interactions on different substrates: a QCM-D experiment.

Quartz crystal microbalance with dissipation (QCM-D) technique is one of the most effective methods to monitor the dynamic behaviors of a layer on a solid surface. Moreover, it has been reported recently that it is able to provide a fingerprint for the peptide-membrane interactions. In this work, QCM-D technique combined with computer simulations was employed to investigate the deposition and transformation of vesicles, as well as the subsequent membrane-melittin interactions on different substrates. A range of substrate surfaces, i.e. naked SiO2 without or with Au/polyelectrolyte coating, were produced. The nature of the substrate determined whether the adsorbed vesicles were present as a high-quality supported bilayer or an assembled vesicle matrix, which consequently influenced the membrane-melittin interactions. It was indicated by the related computer simulations that the lipid packing state of the membrane was a key factor to determine the mechanism of membrane-peptide interactions. Furthermore, this work might be a good example of the application of QCM-D for the exploration of membrane-active peptides.

Protection from lethal challenge in a neonatal mouse model by circulating recombinant form coxsackievirus A16 vaccine candidates.

Circulating coxsackievirus A16 (CA16) is a major cause of hand, foot and mouth disease (HFMD) in South-east Asia. At present, there is no vaccine against CA16. Pathogenic animal models that are sensitive to diverse circulating CA16 viruses would be desirable for vaccine development and evaluation. In this study, we isolated and characterized several circulating CA16 viruses from recent HFMD patients. These CA16 viruses currently circulating in humans were highly pathogenic in a newly developed neonatal mouse model; we also observed and analysed the pathogenesis of representative circulating recombinant form CA16 viruses. An inactivated CA16 vaccine candidate, formulated with alum adjuvant and containing submicrogram quantities of viral proteins, protected neonatal mice born to immunized female mice from lethal-dose challenge with a series of CA16 viruses. Further analysis of humoral immunity showed that antibody elicited from both the immunized dams and their pups could neutralize various lethal viruses by a cytopathic effect in vitro. Moreover, viral titres and loads in the tissues of challenged pups in the vaccine group were far lower than those in the control group, and some were undetectable. This lethal-challenge model using pathogenic CA16 viruses and the vaccine candidates that mediated protection in this model could be useful tools for the future development and evaluation of CA16 vaccines.

Photoinduced reversible shape conversion of silver nanoparticles assisted by TiO2.

Silver nanoprisms were transformed into nanodecahedra through photoinduction of ultraviolet (UV) light in the presence of titanium dioxide (TiO2) quantum dots (QDs). Subsequently, the silver nanodecahedra were reconverted to silver nanoprisms under sodium lamp if there was sufficient citrate in the reaction system. The localized surface plasmon resonance (LSPR) optical properties of silver nanoparticles were tuned during photoinduced shape conversion. The photocatalytic activity of TiO2 QDs assisted the conversion of prisms to decahedra upon UV light irradiation. Nevertheless, the presence of TiO2 did not inhibit the photoinduced reconversion from decahedra to prisms by sodium light. It was demonstrated that citrate was indispensable in the photoinduction process. In addition, oxygen in solution played a vital role in the reversible shape conversion of silver nanoparticles. Moreover, simulated sunlight can convert silver nanoprisms to nanodecahedra instead of UV light with assistance of TiO2 QDs, which would promote the photoinduced reaction of silver nanoparticles based on a natural light source.

Influence of surface chemistry on particle internalization into giant unilamellar vesicles.

Cellular uptake of materials plays a key role in their biomedical applications. In this work, based on the cell-mimic giant unilamellar vesicles (GUVs) and a novel type of microscale materials consisting of stimuli-responsive poly(N-isopropylacrylamide) microgel particles and the incorporated lipids, the influence of particle surface chemistry, including hydrophobic/hydrophilic property and lipid decorations, on the adsorption and consequent internalization of particles into GUVs was investigated. It is found that the decoration of particle surface with lipids facilitates the adsorption of particles on GUV membrane. After that, the hydrophobic property of particle surface further triggers the internalization of particles into GUVs. These results demonstrate the importance of surface properties of particles on their interactions with lipid membranes and are helpful to the understanding of cellular uptake mechanism.

Acceleration effect of reduced graphene oxide on photoinduced synthesis of silver nanoparticles.

The photoinduced growth reaction of silver nanoparticles was accelerated by reduced graphene oxide (RGO) produced from graphene oxide (GO) during the light irradiation process in aqueous solution. X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy demonstrated that RGO was generated in the photoinduced process. The acceleration effect of RGO was investigated through monitoring the extinction spectra of silver nanoparticles during the synthesis process. Moreover, transmission electron microscopy (TEM) was employed to characterize the evolution of morphologies of silver nanoparticles at different irradiation times to demonstrate the effect of RGO. The results indicate that RGO accelerates the photoinduced synthesis of silver nanoparticles. It is proposed that the acceleration effect of RGO on the photoinduced reaction is attributed to the particular property of high electronic conductivity.