More is different: how aggregation turns on the light

The reductionist approach to science seeks to understand the behaviour of systems by studying their individual components. It has been an enormously productive approach, but it is also widely acknowledged now that in some systems the behaviour of interest is an emergent property that cannot be discerned in the separate parts. Biology is replete with such examples, from the flocking of birds to the way metabolic processes in cells rely on a dynamic interplay of proteins and other components.Yet molecular systems do not have to be particularly complex before their properties become more than the sum of the parts. A classic example is the appearance of bulk-like metallic behaviour in small clusters of metal atoms only once they exceed a certain critical size. One of the most striking instances became apparent in 2001, when Ben Zhong Tang of the Hong Kong University of Science and Technology and his co-workers found that heterocyclic silicon-containing molecules called siloles become luminescent as nanoscopic aggregates even though the individual molecules in dilute solution do not emit light [1]. This looked like the opposite of the well-known phenomenon of concentration quenching, in which energy transfer between fluorescent (generally organic) molecules quenches the emission, an effect explained in 1955 [2]. Aggregation-induced ‘switching off’ is intuitively understandable, but ‘switching on’ due to aggregation was more surprising.Yet this effect of ‘aggregation-induced emission’ (AIE), as Tang and colleagues called it, was apparently seen, but not understood, much earlier [3]. In the 1850s, George Stokes noted that some inorganic complexes were fluorescent in the condensed, solid state but not in solution. At first, AIE was seen as a curiosity and deemed likely to be rare. However, subsequent research has shown not only that it is a rather common effect but also that it can be considered just one manifestation of a wide range of behaviours that arise from aggregation—leading to the proposed field of ‘aggregate science’, manifesting at the supramolecular level of small clusters or groups of molecules held together by relatively weak interactions. The field might be considered to illustrate George Whitesides’ notion of a chemistry ‘beyond the molecule’ [4], which bridges disciplines ranging from colloid science to crystal growth, nanotechnology, liquid crystals, photochemistry and molecular biology. At the same time, it echoes the famous insight of physicist Philip Anderson about emergent phenomena and the hierarchical nature of science: ‘More is different’ [5]. An ability to switch properties on and off by controlling intermolecular interactions and aggregation suggests various applications, from optical device technologies to targeted drugs for cancer therapy [6].NSR spoke to Ben Zhong Tang about the origins and possibilities of the field.

NSR: It seems you noticed AIE in 2001 by accident. How did it come about? Tang: Yes, it was serendipity. Development of new light emitters for the fabrication of organic light-emitting diodes was a hot topic at that time. We were trying to make new luminophores [light-emitting molecules] with high efficiencies and novel structures. Attracted by the aesthetically pleasing molecular structures of siloles, I asked my students to prepare various silole compounds. One day, a student told me that he could not see any luminescence when he used a UV lamp to excite the solution of the silole compound he had made. This surprised me, because I myself prepared a silole compound when I was a PhD student and I remember that its crystal was luminescent. I sensed something strange and immediately rushed to the lab. After careful verification and discussion with the student, we concluded that both of us were correct: the silole solution was not luminescent (his observation was right) but the silole powder was emissive (my memory was right). The non-luminescent molecular species in the dilute solution were induced to emit light through formation of aggregates in the solid state. We termed the process aggregation-induced emission or AIE.

A mesoscopic aggregate can have a property that its molecular species does not exhibit at all.—Ben Zhong Tang

Open in a separate windowBen Zhong Tang of the Hong Kong University of Science and Technology, China (Courtesy of Ben Zhong Tang). NSR: The phenomenon seemed to defy conventional expectations. Did you have trouble persuading others—or yourselves!—that it was real? Tang: I initially thought the student might have done something wrong, for the phenomenon he observed was totally unexpected. The common belief in the community of photophysics research is that luminescence from an organic dye generally weakens when its molecules are aggregated, an effect often referred to as aggregation-caused quenching or ACQ. I was shocked when I realized that the silole luminogen was showing an anti-ACQ effect. Still, I felt lucky to encounter something ‘abnormal’. No matter how odd a phenomenon seems, if it can be repeatedly observed, it must be real. We repeated our experiments many times and we were eventually convinced that the AIE effect was true. We had trouble, however, to understand why the silole luminogen behaved in such a way that was diametrically opposed to conventional ACQ. NSR: Are there any historical precedents—experiments in which this effect might have been glimpsed previously, but not recognized as such? Tang: When we published our first AIE paper in 2001, we thought the photophysical effect was unprecedented. However, we gradually found out that similar phenomena had been previously observed by other scientists. For example, in 1853 George Stokes reported in a paper that some inorganic platinocyanide salts ‘are sensitive’ (meaning luminescent in modern terminology) ‘only in the solid state’ but ‘their solutions look like mere water’. Sadly, he didn’t follow it up. Other people have made similar observations in different dye systems, which were, however, not recognized as AIE processes. Partially because of this, we had great difficulty in finding relevant reference papers. As a matter of fact, Stokes’ report, published in the mid-19th century, was not known to us until the middle of 2018. However, we are not surprised by those early works, for we understand that science progresses not in an abrupt but in a continuous way. George Smith articulated this: ‘Very few research breakthroughs are novel. Virtually all of them build on what went on before.’ A discovery is often a happenstance. We happened to have ‘rediscovered’ a very old but largely unnoticed phenomenon. Luckily, we grasped the opportunity to see more and farther by standing on the shoulders of giants.     

Molecular design and application of luminescent materials composed of group 13 elements with an aggregation-induced emission property

Complexation of π-conjugated ligands by metal or semimetal ions leads to the enhancement of the planarity and rigidity of π-conjugated systems. Boron, especially, has played a central role in the design of luminescent main-group complexes. However, these complexes still suffer the disadvantage of aggregation-caused quenching as well as typical organic fluorophores. It has recently been reported that some types of boron complexes exhibit the aggregation-induced emission (AIE) property. Moreover, AIE behavior from complexes and organometallic compounds composed of the other group 13 elements, such as aluminum and gallium, has emerged in this decade. These observations greatly encourage us to develop advanced functional materials based on the group 13 elements. Indeed, recent research has demonstrated that these classes of materials are potentially versatile scaffolds for constructing chromic luminophores, efficiently emissive π-conjugated polymers and so on. This review mainly describes AIE-active group 13 complexes with four-coordinate structures and their application as photo-functional materials. Proposed mechanisms of the origins of AIE behavior are briefly discussed.     

Self-assembly-induced luminescence of Eu3+-complexes and application in bioimaging

Design and engineering of highly efficient emitting materials with assembly-induced luminescence, such as room-temperature phosphorescence (RTP) and aggregation-induced emission (AIE), have stimulated extensive efforts. Here, we propose a new strategy to obtain size-controlled Eu³⁺-complex nanoparticles (Eu-NPs) with self-assembly-induced luminescence (SAIL) characteristics without encapsulation or hybridization. Compared with previous RTP or AIE materials, the SAIL phenomena of increased luminescence intensity and lifetime in aqueous solution for the proposed Eu-NPs are due to the combined effect of self-assembly in confining the molecular motion and shielding the water quenching. As proof of concept, we also show that this system can be further applied in bioimaging, temperature measurement and HClO sensing. The SAIL activity of the rare-earth (RE) system proposed here offers a further step forward on the roadmap for the development of RE light conversion systems and their integration in bioimaging and therapy applications.     

Functional hydrogel coatings

Hydrogels—natural or synthetic polymer networks that swell in water—can be made mechanically, chemically and electrically compatible with living tissues. There has been intense research and development of hydrogels for medical applications since the invention of hydrogel contact lenses in 1960. More recently, functional hydrogel coatings with controlled thickness and tough adhesion have been achieved on various substrates. Hydrogel-coated substrates combine the advantages of hydrogels, such as lubricity, biocompatibility and anti-biofouling properties, with the advantages of substrates, such as stiffness, toughness and strength. In this review, we focus on three aspects of functional hydrogel coatings: (i) applications and functions enabled by hydrogel coatings, (ii) methods of coating various substrates with different functional hydrogels with tough adhesion, and (iii) tests to evaluate the adhesion between functional hydrogel coatings and substrates. Conclusions and outlook are given at the end of this review.     

Interplay between motility and cell-substratum adhesion in amoeboid cells

The effective migration of amoeboid cells requires a fine regulation of cell-substratum adhesion. These entwined processes have been shown to be regulated by a host of biophysical and biochemical cues. Here, we reveal the pivotal role played by calcium-based mechanosensation in the active regulation of adhesion resulting in a high migratory adaptability. Using mechanotactically driven Dictyostelium discoideum amoebae, we uncover the existence of optimal mechanosensitive conditions—corresponding to specific levels of extracellular calcium—for persistent directional migration over physicochemically different substrates. When these optimal mechanosensitive conditions are met, noticeable enhancement in cell migration directionality and speed is achieved, yet with significant differences among the different substrates. In the same narrow range of calcium concentrations that yields optimal cellular mechanosensory activity, we uncovered an absolute minimum in cell-substratum adhesion activity, for all considered substrates, with differences in adhesion strength among them amplified. The blocking of the mechanosensitive ion channels with gadolinium—i.e., the inhibition of the primary mechanosensory apparatus—hampers the active reduction in substrate adhesion, thereby leading to the same undifferentiated and drastically reduced directed migratory response. The adaptive behavioral responses of Dictyostelium cells sensitive to substrates with varying physicochemical properties suggest the possibility of novel surface analyses based on the mechanobiological ability of mechanosensitive and guidable cells to probe substrates at the nanometer-to-micrometer level.     

On the influence of the architecture of poly(ethylene glycol)-based thermoresponsive polymers on cell adhesion

Thermoresponsive polymer surface coatings are a promising tool for cell culture applications. They allow for a mild way of cell detachment that preserves the activity of membrane proteins—a prerequisite for reliable cell analysis. To enlarge the application range of these coatings to cells with different adhesion properties, we synthesized various novel poly(ethylene glycol)-based thermoresponsive polymers and describe how (i) their chemical structure and (ii) their surface density affect their efficiency. In order to quantify the influence of both factors, the time for cell spreading and rounding efficiency were observed. As a result, efficiency of cell rounding, which is closely correlated to cell detachment, is less affected by both factors than the time needed for cell spreading. This time can effectively be adjusted by the molecular architecture which includes the length of the polymer backbone and the side chains. Based on this work, recommendations are given for future optimization of functionality of thermoresponsive polymer coatings for cell culture applications.     

A new twist on graphene: an interview with Pablo Jarillo-Herrero and Allan MacDonald

Graphene is the building block of graphite, made of carbon atoms bonded into sheets of hexagonal rings just a single atom thick. Although such isolated sheets had been predicted for many decades to exist, and had been grown on other surfaces, interest in this material exploded after the discovery in 2004 that single sheets could be made easily and cheaply by separating them mechanically from graphite flakes (a process called exfoliation). Although graphene is often advertised as a ‘wonder material’—electronically conducting, transparent and extremely strong and flexible—much of the interest in it is more fundamental. As a 2D conductor, graphene shows unusual electronic and magnetic properties that enable the study of quantum-mechanical effects of confinement and of correlations between electron motions—some of which might find applications in electronic devices. The excitement of this discovery was reflected in the award of the 2010 Nobel Prize in Physics to two pioneers in the field: Andre Geim and Konstantin Novoselov of the University of Manchester in the UK.This rich behavior is broadened still further when two graphene sheets are brought close enough to interact with one another. In particular, the electronic properties may then depend on the relative orientation of the sheets: how aligned the two ‘honeycomb’ lattices are. Two grids superimposed on one another may create ‘superlattices’: regularities at larger scales than the grid spacing, due to registry (commensurability) between the two at certain angles. This so-called moiré effect is sometimes evident for two closely spaced grid-like fences seen from afar. Experimentally exploring the electronic properties of such ‘twisted bilayer graphene’ requires an ability to precisely control the position and orientation of the two sheets. These phenomena are now recognized as generic to other 2D materials, such as hexagonal sheets of boron nitride. They have revealed a fertile playground for condensed-matter physics. In particular, striking electronic properties appear at certain ‘magic-angle’ twists of the layers.NSR spoke to two of the leading experts in the study of magic-angle twisted bilayer graphene (MATBG): experimentalist Pablo Jarillo-Herrero of the Massachusetts Institute of Technology and theorist Allan MacDonald of the University of Texas at Austin.     

Deep-learning-based information mining from ocean remote-sensing imagery

With the continuous development of space and sensor technologies during the last 40 years, ocean remote sensing has entered into the big-data era with typical five-V (volume, variety, value, velocity and veracity) characteristics. Ocean remote-sensing data archives reach several tens of petabytes and massive satellite data are acquired worldwide daily. To precisely, efficiently and intelligently mine the useful information submerged in such ocean remote-sensing data sets is a big challenge. Deep learning—a powerful technology recently emerging in the machine-learning field—has demonstrated its more significant superiority over traditional physical- or statistical-based algorithms for image-information extraction in many industrial-field applications and starts to draw interest in ocean remote-sensing applications. In this review paper, we first systematically reviewed two deep-learning frameworks that carry out ocean remote-sensing-image classifications and then presented eight typical applications in ocean internal-wave/eddy/oil-spill/coastal-inundation/sea-ice/green-algae/ship/coral-reef mapping from different types of ocean remote-sensing imagery to show how effective these deep-learning frameworks are. Researchers can also readily modify these existing frameworks for information mining of other kinds of remote-sensing imagery.     

Hierarchical self-assembly of actin in micro-confinements using microfluidics

We present a straightforward microfluidics system to achieve step-by-step reaction sequences in a diffusion-controlled manner in quasi two-dimensional micro-confinements. We demonstrate the hierarchical self-organization of actin (actin monomers—entangled networks of filaments—networks of bundles) in a reversible fashion by tuning the Mg²⁺ ion concentration in the system. We show that actin can form networks of bundles in the presence of Mg²⁺ without any cross-linking proteins. The properties of these networks are influenced by the confinement geometry. In square microchambers we predominantly find rectangular networks, whereas triangular meshes are predominantly found in circular chambers.     

Improving the dielectric properties of an electrowetting-on-dielectric microfluidic device with a low-pressure chemical vapor deposited Si3N4 dielectric layer

Dielectric breakdown is a common problem in a digital microfluidic system, which limits its application in chemical or biomedical applications. We propose a new fabrication of an electrowetting-on-dielectric (EWOD) device using Si₃N₄ deposited by low-pressure chemical vapor deposition (LPCVD) as a dielectric layer. This material exhibits a greater relative permittivity, purity, uniformity, and biocompatibility than polymeric films. These properties also increase the breakdown voltage of a dielectric layer and increase the stability of an EWOD system when applied in biomedical research. Medium droplets with mouse embryos were manipulated in this manner. The electrical properties of the Si₃N₄ dielectric layer—breakdown voltage, refractive index, relative permittivity, and variation of contact angle with input voltage—were investigated and compared with a traditional Si₃N₄ dielectric layer deposited as a plasma-enhanced chemical vapor deposition to confirm the potential of LPCVD Si₃N₄ applied as the dielectric layer of an EWOD digital microfluidic system.     

Agar-polydimethylsiloxane devices for quantitative investigation of oviposition behaviour of adult Drosophila melanogaster

Drosophila melanogaster (fruit fly) is a model organism and its behaviours including oviposition (egg-laying) on agar substrates have been widely used for assessment of a variety of biological processes in flies. Physical and chemical properties of the substrate are the dominant factors affecting Drosophila''s oviposition, but they have not been investigated precisely and parametrically with the existing manual approaches. As a result, many behavioral questions about Drosophila oviposition, such as the combined effects of the aforementioned substrate properties (e.g., exposure area, sugar content, and stiffness) on oviposition and viability, and their threshold values, are yet to be answered. In this paper, we have devised a simple, easily implementable, and novel methodology that allows for modification of physical and chemical composition of agar substrates in order to quantitatively study survival and oviposition of adult fruit flies in an accurate and repeatable manner. Agar substrates have been modified by surface patterning using single and hexagonally arrayed through-hole polydimethylsiloxane (PDMS) membranes with various diameters and interspacing, as well as by substrate stiffness and sugar content modification via alteration of chemical components. While pure PDMS substrates showed a significant lethal effect on flies, a 0.5 mm diameter through-hole access to agar was found to abruptly increase the survival of adult flies to more than 93%. Flies avoided ovipositing on pure PDMS and on top of substrates with 0.5 mm diameter agar exposure areas. At a hole diameter of 2 mm (i.e., 0.25% exposure area) or larger, eggs were observed to be laid predominately inside the through-holes and along the edges of the PDMS-agar interface, showing a trending increase in site selection with 4 mm (i.e., 1% exposure area threshold) demonstrating natural oviposition rates similar to pure agar. The surface-modified agar-PDMS hybrid devices and the threshold values reported for the substrate physical and chemical conditions affecting oviposition are novel; therefore, we advocate their use for future in-depth studies of oviposition behaviour in Drosophila melanogaster with accuracy and repeatability. The technique is also useful for development of novel assays for learning and decision-making studies as well as miniaturized devices for self-assembly of eggs and embryonic developmental investigations.     

Red blood cell membrane-camouflaged nanoparticles loaded with AIEgen and Poly(I : C) for enhanced tumoral photodynamic-immunotherapy

Red blood cell (RBC)-mimicking nanoparticles (NPs) offer a promising platform for drug delivery because of their prolonged circulation time, reduced immunogenicity and specific targeting ability. Herein, we report the design and preparation of RBC membrane-bound NPs (M@AP), for tumoral photodynamic-immunotherapy. The M@AP is formed by self-assembly of the positively charged aggregation-induced emission luminogen (AIEgen) (named P2-PPh3) and the negatively charged polyinosinic : polycytidylic acid (Poly(I : C)), followed by RBC membrane encapsulation. P2-PPh3 is an AIE-active conjugated polyelectrolyte with additional photosensitizing ability for photodynamic therapy (PDT), while Poly(I : C) serves as an immune-stimulant to stimulate both tumor and immune cells to activate immunity, and thus reduces tumor cell viability. When applied in tumor-bearing mice, the M@AP NPs are enriched in both the tumor region as a result of an enhanced permeability and retention (EPR) effect, and the spleen because of the homing effect of the RBC-mimicking shell. Upon light irradiation, P2-PPh3 promotes strong ROS generation in tumor cells, inducing the release of tumor antigens (TA). The anti-tumor immunity is further enhanced by the presence of Poly(I : C) in M@AP. Thus, this strategy combines the PDT properties of the AIE-active polyelectrolyte and immunotherapy properties of Poly(I : C) to achieve synergistic activation of the immune system for anti-tumor activity, providing a novel strategy for tumor treatment.     

Trapping endoplasmic reticulum with amphiphilic AIE-active sensor via specific interaction of ATP-sensitive potassium (KATP)

The current aggregation-induced emission luminogens (AIEgens) sometimes suffer from poor targeting selectivity due to undesirable aggregation in the hydrophilic biosystem with ‘always-on’ fluorescence or unspecific aggregation in the lipophilic organelle with prematurely activated fluorescence. Herein, we report an unprecedented ‘amphiphilic AIEgen’ sensor QM-SO₃-ER based on the AIE building block of quinoline-malononitrile (QM). The introduced hydrophilic sulfonate group can well control the specific solubility in a hydrophilic system with desirable initial ‘fluorescence-off’ state. Moreover, the incorporated p-toluenesulfonamide group plays two roles: enhancing the lipophilic dispersity, and behaving as binding receptor to the adenosine triphosphate (ATP)-sensitive potassium (K_ATP) on the endoplasmic reticulum (ER) membrane to generate the docking assay confinement effect with targetable AIE signal. The amphiphilic AIEgen has for the first time settled down the predicament of unexpected ‘always-on’ fluorescence in the aqueous system and the untargetable aggregation signal in the lipophilic organelle before binding to ER, thus successfully overcoming the bottleneck of AIEgens'' targetability.     

Ionic current devices—Recent progress in the merging of electronic,microfluidic, and biomimetic structures

We review the recent progress in the emerging area of devices and circuits operating on the basis of ionic currents. These devices operate at the intersection of electrochemistry, electronics, and microfluidics, and their potential applications are inspired by essential biological processes such as neural transmission. Ionic current rectification has been demonstrated in diode-like devices containing electrolyte solutions, hydrogel, or hydrated nanofilms. More complex functions have been realized in ionic current based transistors, solar cells, and switching memory devices. Microfluidic channels and networks—an intrinsic component of the ionic devices—could play the role of wires and circuits in conventional electronics.     

Lipid–oligonucleotide conjugates for bioapplications

Lipid–oligonucleotide conjugates (LONs) are powerful molecular-engineering materials for various applications ranging from biosensors to biomedicine. Their unique amphiphilic structures enable the self-assembly and the conveyance of information with high fidelity. In particular, LONs present remarkable potential in measuring cellular mechanical forces and monitoring cell behaviors. LONs are also essential sensing tools for intracellular imaging and have been employed in developing cell-surface-anchored DNA nanostructures for biomimetic-engineering studies. When incorporating therapeutic oligonucleotides or small-molecule drugs, LONs hold promise for targeted therapy. Moreover, LONs mediate the controllable assembly and fusion of vesicles based on DNA-strand displacements, contributing to nanoreactor construction and macromolecule delivery. In this review, we will summarize the general synthesis strategies of LONs, provide some characterization analysis and emphasize recent advances in bioanalytical and biomedical applications. We will also consider the relevant challenges and suggest future directions for building better functional LONs in nanotechnology and materials-science applications.     

Microfluidic production of single micrometer-sized hydrogel beads utilizing droplet dissolution in a polar solvent

In this study, a microfluidic process is proposed for preparing monodisperse micrometer-sized hydrogel beads. This process utilizes non-equilibrium aqueous droplets formed in a polar organic solvent. The water-in-oil droplets of the hydrogel precursor rapidly shrunk owing to the dissolution of water molecules into the continuous phase. The shrunken and condensed droplets were then gelled, resulting in the formation of hydrogel microbeads with sizes significantly smaller than the initial droplet size. This study employed methyl acetate as the polar organic solvent, which can dissolve water at 8%. Two types of monodisperse hydrogel beads—Ca-alginate and chitosan—with sizes of 6–10 μm (coefficient of variation < 6%) were successfully produced. In addition, we obtained hydrogel beads with non-spherical morphologies by controlling the degree of droplet shrinkage at the time of gelation and by adjusting the concentration of the gelation agent. Furthermore, the encapsulation and concentration of DNA molecules within the hydrogel beads were demonstrated. The process presented in this study has great potential to produce small and highly concentrated hydrogel beads that are difficult to obtain by using conventional microfluidic processes.     

Thermal-siphon phenomenon and thermal/electric conduction in complex networks

In past decades, a lot of studies have been carried out on complex networks and heat conduction in regular lattices. However, very little attention has been paid to the heat conduction in complex networks. In this work, we study (both thermal and electric) energy transport in physical networks rewired from 2D regular lattices. It is found that the network can be transferred from a good conductor to a poor conductor, depending on the rewired network structure and coupling scheme. Two interesting phenomena were discovered: (i) the thermal-siphon effect—namely the heat flux can go from a low-temperature node to a higher-temperature node and (ii) there exits an optimal network structure that displays small thermal conductance and large electrical conductance. These discoveries reveal that network-structured materials have great potential in applications in thermal-energy management and thermal-electric-energy conversion.     

Evaluation of Anti-hypertrophic Potential of Enicostemma littorale Blume on Isoproterenol Induced Cardiac Hypertrophy

The main objective of this study is to evaluate the anti-hypertrophic potential of the aqueous extract of Enicostemma littorale (E. littorale) against isoproterenol induced cardiac hypertrophic rat models (male albino Wistar rats) through biochemical investigations. Aqueous extract of E. littorale known for various beneficial properties was administered (100 mg/kg, 12 days, oral) to isoproterenol (ISO) induced cardiac hypertrophic rats (low ISO—60 mg/kg, 12 days and high ISO—100 mg/kg, 12 days, subcutaneous) and were compared with group that was treated with the reference drug, Losartan (10 mg kg, administered for 12 days, oral). The anti-hypertrophic effect of E. littorale was evaluated by analysing the morphometric indices of the heart, ECG tracings, changes in blood biochemical parameters viz., serum glucose, serum total protein, serum albumin, lipid profile, cardiac specific enzymes (SGOT, SGPT and LDH) and histopathological examination of the heart tissue. The results fundamentally revealed that the plant extract efficiently ameliorated cardiac hypertrophy induced by ISO injected in experimental rats. The outcomes of biochemical investigations of this study highlighted the association between the hypertrophic β-adrenergic receptor signalling (β-AR) and the 5′ AMP-activated protein kinase (AMPK)—peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) axis in the metabolism of cardiac fibrosis and hypertrophy. This β-AR/AMPK-PGC1α signalling stem can serve as a key target in ameliorating cardiac hypertrophy through focus on its principal regulators. To add, we also propose that the glycoside, swertiamarin present in this plant with the reported anti-fibrotic potential in liver can be further isolated and evaluated for its anti-hypertrophic potential to treat cardiac hypertrophy.     

A microfluidic platform for size-dependent generation of droplet interface bilayer networks on rails

Droplet interface bilayer (DIB) networks are emerging as a cornerstone technology for the bottom up construction of cell-like and tissue-like structures and bio-devices. They are an exciting and versatile model-membrane platform, seeing increasing use in the disciplines of synthetic biology, chemical biology, and membrane biophysics. DIBs are formed when lipid-coated water-in-oil droplets are brought together—oil is excluded from the interface, resulting in a bilayer. Perhaps the greatest feature of the DIB platform is the ability to generate bilayer networks by connecting multiple droplets together, which can in turn be used in applications ranging from tissue mimics, multicellular models, and bio-devices. For such applications, the construction and release of DIB networks of defined size and composition on-demand is crucial. We have developed a droplet-based microfluidic method for the generation of different sized DIB networks (300–1500 pl droplets) on-chip. We do this by employing a droplet-on-rails strategy where droplets are guided down designated paths of a chip with the aid of microfabricated grooves or “rails,” and droplets of set sizes are selectively directed to specific rails using auxiliary flows. In this way we can uniquely produce parallel bilayer networks of defined sizes. By trapping several droplets in a rail, extended DIB networks containing up to 20 sequential bilayers could be constructed. The trapped DIB arrays can be composed of different lipid types and can be released on-demand and regenerated within seconds. We show that chemical signals can be propagated across the bio-network by transplanting enzymatic reaction cascades for inter-droplet communication.     

Interplay Between Inflammation and Hemostasis in Patients with Coronary Artery Disease

Coronary artery disease (CAD) is a global epidemic currently. This study was planned to evaluate markers of inflammation and hemostasis and their possible association, if any, in patients with CAD. The study was carried out in 60 patients with acute myocardial infarction (AMI) and 60 age and gender matched controls. The following parameters were assayed in all study subjects-inflammatory-interleukin (IL)-10, high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-α, fibrinogen; hemostatic-fibrinogen, fibrin D-dimer and a novel risk factor—homocysteine. Inflammatory markers (hs-CRP, TNF-α and IL-10), fibrinogen, fibrin D-dimer and homocysteine levels were significantly higher in the patients with AMI, as compared with controls. A positive correlation was observed between D-dimer and the inflammatory markers—hs-CRP and TNF-α. Upon multivariate analysis, TNF-α emerged as the best determinant of CAD in our study. Our results indicate that there is a possible interplay of inflammation and hemostasis in CAD, underlining their synergistic role in the pathogenesis of CAD.