Intravital imaging of splenic classical monocytes modifying the hepatic CX3CR1+ cells motility to exacerbate liver fibrosis via spleen-liver axis.

CX3CR1+ cells play a crucial role in liver fibrosis progression. However, changes in the migratory behavior and spatial distribution of spleen-derived and hepatic CX3CR1+ cells in the fibrotic liver as well as their influence on the liver fibrosis remain unclear. METHODS: The CX3CR1GFP/+ transgenic mice and CX3CR1-KikGR transgenic mice were used to establish the CCl4-induced liver fibrosis model. Splenectomy, adoptive transfusion of splenocytes, in vivo photoconversion of splenic CX3CR1+ cells and intravital imaging were performed to study the spatial distribution, migration and movement behavior, and regulatory function of CX3CR1+ cells in liver fibrosis. RESULTS: Intravital imaging revealed that the CX3CR1GFP cells accumulated into the fibrotic liver and tended to accumulate towards the central vein (CV) in the hepatic lobules. Two subtypes of hepatic CX3CR1+ cells existed in the fibrotic liver. The first subtype was the interacting CX3CR1GFP cells, most of which were observed to distribute in the liver parenchyma and had a higher process velocity; the second subtype was mobile CX3CR1GFP cells, most of which were present in the hepatic vessels with a faster moving speed. Splenectomy ameliorated liver fibrosis and decreased the number of CX3CR1+ cells in the fibrotic liver. Moreover, splenectomy rearranged CX3CR1GFP cells to the boundary of the hepatic lobule, reduced the process velocity of interacting CX3CR1GFP cells and decreased the number and mobility of mobile CX3CR1GFP cells in the fibrotic liver. Transfusion of spleen-derived classical monocytes increased the process velocity and mobility of hepatic endogenous CX3CR1GFP cells and facilitated liver fibrosis progression via the production of proinflammatory and profibrotic cytokines. The photoconverted splenic CX3CR1+ KikRed+ cells were observed to leave the spleen, accumulate into the fibrotic liver and contact with hepatic CX3CR1+ KikGreen+ cells during hepatic fibrosis. CONCLUSION: The splenic CX3CR1+ monocytes with classical phenotype migrated from the spleen to the fibrotic liver, modifying the migratory behavior of hepatic endogenous CX3CR1GFP cells and exacerbating liver fibrosis via the secretion of cytokines. This study reveals that splenic CX3CR1+ classical monocytes are a key driver of liver fibrosis via the spleen-liver axis and may be potential candidate targets for the treatment of chronic liver fibrosis.

Intravital imaging of the functions of immune cells in the tumor microenvironment during immunotherapy.

Cancer immunotherapy has developed rapidly in recent years and stands as one of the most promising techniques for combating cancer. To develop and optimize cancer immunotherapy, it is crucial to comprehend the interactions between immune cells and tumor cells in the tumor microenvironment (TME). The TME is complex, with the distribution and function of immune cells undergoing dynamic changes. There are several research techniques to study the TME, and intravital imaging emerges as a powerful tool for capturing the spatiotemporal dynamics, especially the movement behavior and the immune function of various immune cells in real physiological state. Intravital imaging has several advantages, such as high spatio-temporal resolution, multicolor, dynamic and 4D detection, making it an invaluable tool for visualizing the dynamic processes in the TME. This review summarizes the workflow for intravital imaging technology, multi-color labeling methods, optical imaging windows, methods of imaging data analysis and the latest research in visualizing the spatio-temporal dynamics and function of immune cells in the TME. It is essential to investigate the role played by immune cells in the tumor immune response through intravital imaging. The review deepens our understanding of the unique contribution of intravital imaging to improve the efficiency of cancer immunotherapy.

Surface interaction mechanisms of air bubbles, asphaltenes and oil drops in aqueous solutions with implications for interfacial engineering processes.

HYPOTHESIS: Surface interactions of bubbles and oil with interface-active species like asphaltenes influence many interfacial phenomena in various engineering processes. It holds both fundamental and practical significance to quantitatively characterize these interactions. EXPERIMENTS: The surface forces of air bubbles, asphaltenes and asphaltenes-toluene droplets in various aqueous solutions have been quantified using an integrated thin film drainage apparatus and an atomic force microscope coupled with bubble probe. The effects of asphaltenes concentration, pH, salinity, Ca2+ ions and surfactants have been examined. FINDINGS: Hydrophobic interaction drives attachment of bubbles and asphaltenes surfaces or oil droplets under high salinity condition. Increasing asphaltenes concentration in oil droplets enhances their hydrophobic attraction with bubbles due to strengthened asphaltenes adsorption and aggregation at oil-water interface. Increasing pH weakens the hydrophobic interaction as oil surfaces become more negatively charged and less hydrophobic. Under low salinity condition, strong electrical double layer and van der Waals repulsion inhibits the bubble-oil droplet contact. Introducing Ca2+ ions and surfactants leads to strong steric repulsion, preventing bubble-oil contact. This research has advanced our mechanistic understanding of how bubbles and oil droplets interact in aqueous systems and offers useful insights to modulate such interactions in oil production, water treatment and other interfacial processes.

A pH and Temperature Dual-Responsive Microgel-Embedded, Adhesive, and Tough Hydrogel for Drug Delivery and Wound Healing.

Stimuli-responsive hydrogels have attracted much attention over the past decade for potential bioengineering applications such as wound dressing and drug delivery. In this work, a pH and temperature dual-responsive microgel-embedded hydrogel has been fabricated by incorporating poly(N-isopropylacrylamide-co-acrylic acid) (PNIPAAm-co-AAc) based microgel particles into polyacrylamide (PAAm)/chitosan (CS) semi-interpenetrating polymer network (semi-IPN), denoted as microgel@PAM/CS. The resultant hydrogel possesses excellent mechanical properties including stretchability, compressibility, and elasticity. In addition, the microgel@PAM/CS hydrogels can tightly adhere to the surfaces of a variety of tissues such as porcine skin, kidney, intestine, liver, and heart. Moreover, it shows controlled dual-drug release profile of both bovine serum albumin (BSA) (as a model protein) and sulfamethoxazole (SMZ), an antibiotic. Excellent antimicrobial properties are obtained for SMZ-loaded microgel@PAM/CS hydrogels. Compared with traditional drug administration methods such as by mouth, injection, and inhalation, the microgel@PAM/CS hydrogels possess advantages such as higher drug loading efficiency (by more than 80%) and controllable and sustained (over 48 h) release. The microgel@PAM/CS hydrogels can significantly enhance the wound healing process. This work provides a facile approach for the fabrication of multifunctional stimuli-responsive microparticle-embedded hydrogels with semi-IPN structures, and the as-prepared microgel@PAM/CS hydrogels have great potential for applications as smart wound dressing materials in biomedical engineering.

Probing and Manipulating Noncovalent Interactions in Functional Polymeric Systems.

Noncovalent interactions, which usually feature tunable strength, reversibility, and environmental adaptability, have been recognized as driving forces in a variety of biological and chemical processes, contributing to the recognition between molecules, the formation of molecule clusters, and the establishment of complex structures of macromolecules. The marriage of noncovalent interactions and conventional covalent polymers offers the systems novel mechanical, physicochemical, and biological properties, which are highly dependent on the binding mechanisms of the noncovalent interactions that can be illuminated via quantification. This review systematically discusses the nanomechanical characterization of typical noncovalent interactions in polymeric systems, mainly through direct force measurements at microscopic, nanoscopic, and molecular levels, which provide quantitative information (e.g., ranges, strengths, and dynamics) on the binding behaviors. The fundamental understandings of intermolecular and interfacial interactions are then correlated to the macroscopic performances of a series of noncovalently bonded polymers, whose functions (e.g., stimuli-responsiveness, self-healing capacity, universal adhesiveness) can be customized through the manipulation of the noncovalent interactions, providing insights into the rational design of advanced materials with applications in biomedical, energy, environmental, and other engineering fields.

Modeling HPV-Associated Disease and Cancer Using the Cottontail Rabbit Papillomavirus.

Approximately 5% of all human cancers are attributable to human papillomavirus (HPV) infections. HPV-associated diseases and cancers remain a substantial public health and economic burden worldwide despite the availability of prophylactic HPV vaccines. Current diagnosis and treatments for HPV-associated diseases and cancers are predominantly based on cell/tissue morphological examination and/or testing for the presence of high-risk HPV types. There is a lack of robust targets/markers to improve the accuracy of diagnosis and treatments. Several naturally occurring animal papillomavirus models have been established as surrogates to study HPV pathogenesis. Among them, the Cottontail rabbit papillomavirus (CRPV) model has become known as the gold standard. This model has played a pivotal role in the successful development of vaccines now available to prevent HPV infections. Over the past eighty years, the CRPV model has been widely applied to study HPV carcinogenesis. Taking advantage of a large panel of functional mutant CRPV genomes with distinct, reproducible, and predictable phenotypes, we have gained a deeper understanding of viral-host interaction during tumor progression. In recent years, the application of genome-wide RNA-seq analysis to the CRPV model has allowed us to learn and validate changes that parallel those reported in HPV-associated cancers. In addition, we have established a selection of gene-modified rabbit lines to facilitate mechanistic studies and the development of novel therapeutic strategies. In the current review, we summarize some significant findings that have advanced our understanding of HPV pathogenesis and highlight the implication of the development of novel gene-modified rabbits to future mechanistic studies.

Stretchable, compressible, and conductive hydrogel for sensitive wearable soft sensors.

Conductive hydrogels hold great promises in wearable soft electronics. However, the weak mechanical properties, low sensitivity and the absence of multifunctionalities (e.g., self-healing, self-adhesive, etc.) of the conventional conductive hydrogels limit their applications. Thus, developing multifunctional hydrogels may address some of these technical issues. In this work, a multifunctional conductive hydrogel strain sensor is fabricated by incorporating a conductive polymer Poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT: PSS) into a mechanically robust poly (vinyl alcohol) (PVA)/ poly (acrylic acid) (PAA) double network (DN) hydrogel. The as-prepared hydrogel sensor could span a wide spectrum of mechanical properties by simply tuning the polymer composition and the number of freezing-thawing cycles. In addition, the dynamic hydrogen bonding interactions endow the hydrogel sensor with self-healing property and reversible adhesiveness on diverse substrates. Moreover, the hydrogel sensor shows high sensitivity (Gauge Factor from 2.21 to 3.82) and can precisely detect some subtle human motions (e.g., pulse and vocal cord vibration). This work provides useful insights into the development of conductive hydrogel-based wearable soft electronics.

Probing Hydrophobic Interactions between Polymer Surfaces and Air Bubbles or Oil Droplets: Effects of Molecular Weight and Surfactants.

Hydrophobic interaction plays an important role in numerous interfacial phenomena and biophysical and industrial processes. In this work, polystyrene (PS) was used as a model hydrophobic polymer for investigating its hydrophobic interaction with highly deformable objects (i.e., air bubbles and oil droplets) in aqueous solutions. The effects of polymer molecular weight, solvent (i.e., addition of ethanol to water), the presence of surface-active species, and hydrodynamic conditions were investigated, via direct surface force measurements using the bubble/drop probe atomic force microscopy (AFM) technique and theoretical calculations based on the Reynolds lubrication theory and augmented Young-Laplace equation by including the effect of disjoining pressure. It was found that the PS of low molecular weight (i.e., PS590 and PS810) showed slightly weaker hydrophobic interactions with air bubbles or oil droplets, as compared to glassy PS of higher molecular weight (i.e., PS1110, PS2330, PS46300, and PS1M). The hydrophobic interaction between PS and air bubbles in a 1 M NaCl aqueous solution with 10 vol % ethanol was weaker than that in the bare aqueous solution. Such effects on the hydrophobic interactions are possibly achieved by influencing the structuring/ordering of water molecules close to the hydrophobic polymer surfaces by tuning the surface chain mobility and surface roughness of polymers. It was found that the addition of three surface-active species, i.e., cetyltrimethylammonium chloride (CTAC), Pluronic F-127, and sodium dodecyl sulfate (SDS), to the aqueous media could suppress the attachment of the hydrophobic polymer and air bubbles or oil droplets, most likely caused by the additional steric repulsion due to the adsorbed surface-active species at the bubble/polymer/oil interfaces. Our results have improved the fundamental understanding of the interaction mechanisms between hydrophobic polymers and gas bubbles or oil droplets, with useful implications on developing effective methods for modulating the related interfacial interactions in many engineering applications.

Coacervate-Based Instant and Repeatable Underwater Adhesive with Anticancer and Antibacterial Properties.

Underwater adhesion is a great challenge for the development of adhesives as the attractive interfacial intermolecular interactions are usually weakened by the surface hydration layer. The coacervation process of sessile organisms like marine mussels and sandcastle worms has inspired substantial research interest in the fabrication of long-lasting underwater adhesives, but they generally suffer from time-consuming curing triggered by surrounding environmental changes and cannot reserve the adhesiveness once damaged. Herein, an instant and repeatable underwater adhesive was developed based on the coacervation of tannic acid (TA) and poly(ethylene glycol)77-b-poly(propylene glycol)29-b-poly(ethylene glycol)77 (PEG-PPG-PEG, F68), which was driven by hydrogen-bonding interaction, and the hydrophobic cores of F68 micelles offered an additional cross-linking to enhance the mechanical properties. The TA-F68 coacervates could be facilely painted on different substrates, exhibiting robust and instant underwater adhesion (with adhesion strength up to 1.1 MPa on porcine skin) and excellent repeatability (at least 1000 cycles), superior to the previously reported coacervates. Due to the biological activities of TA, the underwater adhesive displayed innate anticancer and antibacterial properties against different types of cancer cells and bacteria, showing great potential for diverse biomedical applications, such as injectable drug carriers, tissue glues, and wound dressings.

Surface interaction mechanisms in mineral flotation: Fundamentals, measurements, and perspectives.

As non-renewable natural resources, minerals are essential in a broad range of biological and technological applications. The surface interactions of mineral particles with other objects (e.g., solids, bubbles, reagents) in aqueous suspensions play a critical role in mediating many interfacial phenomena involved in mineral flotation. In this work, we have reviewed the fundamentals of surface forces and quantitative surface property-force relationship of minerals, and the advances in the quantitative measurements of interaction forces of mineral-mineral, bubble-mineral and mineral-reagent using nanomechanical tools such as surface forces apparatus (SFA) and atomic force microscope (AFM). The quantitative correlation between surface properties of minerals at the solid/water interface and their surface interaction mechanisms with other objects in complex aqueous media at the nanoscale has been established. The existing challenges in mineral flotation such as characterization of anisotropic crystal plane or heterogeneous surface, low recovery of fine particle flotation, and in-situ electrochemical characterization of collectorless flotation as well as the future work to resolve the challenges based on the understanding and modulation of surface forces of minerals have also been discussed. This review provides useful insights into the fundamental understanding of the intermolecular and surface interaction mechanisms involved in mineral processing, with implications for precisely modulating related interfacial interactions towards the development of highly efficient industrial processes and chemical additives.

Gene Editing in Rabbits: Unique Opportunities for Translational Biomedical Research.

The rabbit is a classic animal model for biomedical research, but the production of gene targeted transgenic rabbits had been extremely challenging until the recent advent of gene editing tools. More than fifty gene knockout or knock-in rabbit models have been reported in the past decade. Gene edited (GE) rabbit models, compared to their counterpart mouse models, may offer unique opportunities in translational biomedical research attributed primarily to their relatively large size and long lifespan. More importantly, GE rabbit models have been found to mimic several disease pathologies better than their mouse counterparts particularly in fields focused on genetically inherited diseases, cardiovascular diseases, ocular diseases, and others. In this review we present selected examples of research areas where GE rabbit models are expected to make immediate contributions to the understanding of the pathophysiology of human disease, and support the development of novel therapeutics.

Adhesive Coacervates Driven by Hydrogen-Bonding Interaction.

Coacervation plays a critical role in numerous biological activities such as constructing biological tissues and achieving robust wet adhesion of marine sessile organisms, which conventionally occurs when oppositely charged polyelectrolytes are mixed in aqueous solutions driven by electrostatic attraction. Here, a novel type of adhesive coacervate is reported, driven by hydrogen-bonding interactions, readily formed by mixing silicotungstic acid and nonionic polyethylene glycol in water, providing a new approach for developing coacervates from nonionic systems. The as-prepared coacervate is easily paintable underwater, show strong wet adhesion to diverse substrates, and has been successfully applied as a hemostatic agent to treat organ injuries without displaying hemolytic activity, while with inherent antimicrobial properties thus avoiding inflammations and infections due to microorganism accumulation. This work demonstrates that coacervation can occur in salt-free environments via non-electrostatic interactions, providing a new platform for engineering multifunctional coacervate materials as tissue glues, wound dressings and membrane-free cell systems.

Late INa Blocker GS967 Supresses Polymorphic Ventricular Tachycardia in a Transgenic Rabbit Model of Long QT Type 2.

BACKGROUND: Long QT syndrome has been associated with sudden cardiac death likely caused by early afterdepolarizations (EADs) and polymorphic ventricular tachycardias (PVTs). Suppressing the late sodium current (INaL) may counterbalance the reduced repolarization reserve in long QT syndrome and prevent EADs and PVTs. METHODS: We tested the effects of the selective INaL blocker GS967 on PVT induction in a transgenic rabbit model of long QT syndrome type 2 using intact heart optical mapping, cellular electrophysiology and confocal Ca2+ imaging, and computer modeling. RESULTS: GS967 reduced ventricular fibrillation induction under a rapid pacing protocol (n=7/14 hearts in control versus 1/14 hearts at 100 nmol/L) without altering action potential duration or restitution and dispersion. GS967 suppressed PVT incidences by reducing Ca2+-mediated EADs and focal activity during isoproterenol perfusion (at 30 nmol/L, n=7/12 and 100 nmol/L n=8/12 hearts without EADs and PVTs). Confocal Ca2+ imaging of long QT syndrome type 2 myocytes revealed that GS967 shortened Ca2+ transient duration via accelerating Na+/Ca2+ exchanger (INCX)-mediated Ca2+ efflux from cytosol, thereby reducing EADs. Computer modeling revealed that INaL potentiates EADs in the long QT syndrome type 2 setting through (1) providing additional depolarizing currents during action potential plateau phase, (2) increasing intracellular Na+ (Nai) that decreases the depolarizing INCX thereby suppressing the action potential plateau and delaying the activation of slowly activating delayed rectifier K+ channels (IKs), suggesting important roles of INaL in regulating Nai. CONCLUSIONS: Selective INaL blockade by GS967 prevents EADs and abolishes PVT in long QT syndrome type 2 rabbits by counterbalancing the reduced repolarization reserve and normalizing Nai. Graphic Abstract: A graphic abstract is available for this article.

Short-Long Heart Rate Variation Increases Dispersion of Action Potential Duration in Long QT Type 2 Transgenic Rabbit Model.

The initiation of polymorphic ventricular tachycardia in long QT syndrome type 2 (LQT2) has been associated with a characteristic ECG pattern of short-long RR intervals. We hypothesize that this characteristic pattern increases APD dispersion in LQT2, thereby promoting arrhythmia. We investigated APD dispersion and its dependence on two previous cycle lengths (CLs) in transgenic rabbit models of LQT2, LQT1, and their littermate controls (LMC) using random stimulation protocols. The results show that the short-long RR pattern was associated with a larger APD dispersion in LQT2 but not in LQT1 rabbits. The multivariate analyses of APD as a function of two previous CLs (APDn = C + α1CLn-1 + α2CLn-2) showed that α1 (APD restitution slope) is largest and heterogeneous in LQT2 but uniform in LQT1, enhancing APD dispersion under long CLn-1 in LQT2. The α2 (short-term memory) was negative in LQT2 while positive in LQT1, and the spatial pattern of α1 was inversely correlated to α2 in LQT2, which explains why a short-long combination causes a larger APD dispersion in LQT2 but not in LQT1 rabbits. In conclusion, short-long RR pattern increased APD dispersion only in LQT2 rabbits through heterogeneous APD restitution and the short-term memory, underscoring the genotype-specific triggering of arrhythmias in LQT syndrome.

Papillomavirus can be transmitted through the blood and produce infections in blood recipients: Evidence from two animal models.

Human papillomaviruses (HPV) contribute to most cervical cancers and are considered to be sexually transmitted. However, papillomaviruses are often found in cancers of internal organs, including the stomach, raising the question as to how the viruses gain access to these sites. A possible connection between blood transfusion and HPV-associated disease has not received much attention. Here we show, in rabbit and mouse models, that blood infected with papillomavirus yields infections at permissive sites with detectable viral DNA, RNA transcripts, and protein products. The rabbit skin tumours induced via blood infection displayed decreased expression of SLN, TAC1, MYH8, PGAM2, and APOBEC2 and increased expression of SDRC7, KRT16, S100A9, IL36G, and FABP9, as seen in tumours induced by local infections. Furthermore, we demonstrate that blood from infected mice can transmit the infection to uninfected animals. Finally, we demonstrate the presence of papillomavirus infections and virus-induced hyperplasia in the stomach tissues of animals infected via the blood. These results indicate that blood transmission could be another route for papillomavirus infection, implying that the human blood supply, which is not screened for papillomaviruses, could be a potential source of HPV infection as well as subsequent cancers in tissues not normally associated with the viruses.

Author Correction: The wide utility of rabbits as models of human diseases.

This article was originally published under a CC BY-NC-SA License, but has now been made available under a CC BY 4.0 License.

The rabbit papillomavirus model: a valuable tool to study viral-host interactions.

Cottontail rabbit papillomavirus (CRPV) was the first DNA virus shown to be tumorigenic. The virus has since been renamed and is officially known as Sylvilagus floridanus papillomavirus 1 (SfPV1). Since its inception as a surrogate preclinical model for high-risk human papillomavirus (HPV) infections, the SfPV1/rabbit model has been widely used to study viral-host interactions and has played a pivotal role in the successful development of three prophylactic virus-like particle vaccines. In this review, we will focus on the use of the model to gain a better understanding of viral pathogenesis, gene function and host immune responses to viral infections. We will discuss the application of the model in HPV-associated vaccine testing, in therapeutic vaccine development (using our novel HLA-A2.1 transgenic rabbits) and in the development and validation of novel anti-viral and anti-tumour compounds. Our goal is to demonstrate the role the SfPV1/rabbit model has played, and continues to play, in helping to unravel the intricacies of papillomavirus infections and to develop tools to thwart the disease. This article is part of the theme issue 'Silent cancer agents: multi-disciplinary modelling of human DNA oncoviruses'.

Transient Outward K+ Current (Ito) Underlies the Right Ventricular Initiation of Polymorphic Ventricular Tachycardia in a Transgenic Rabbit Model of Long-QT Syndrome Type 1.

BACKGROUND: Sudden death in long-QT syndrome type 1 (LQT1), an inherited disease caused by loss-of-function mutations in KCNQ1, is triggered by early afterdepolarizations (EADs) that initiate polymorphic ventricular tachycardia (pVT). We investigated ionic mechanisms that underlie pVT in LQT1 using a transgenic rabbit model of LQT1. METHODS: Optical mapping, cellular patch clamping, and computer modeling were used to elucidate the mechanisms of EADs in transgenic LQT1 rabbits. RESULTS: The results showed that shorter action potential duration in the right ventricle (RV) was associated with focal activity during pVT initiation. RV cardiomyocytes demonstrated higher incidence of EADs under 50 nmol/L isoproterenol. Voltage-clamp studies revealed that the transient outward potassium current (Ito) magnitude was 28% greater in RV associated with KChiP2 but with no differences in terms of calcium-cycling kinetics and other sarcolemmal currents. Perfusing with the Ito blocker 4-aminopyridine changed the initial focal sites of pVT from the RV to the left ventricle, corroborating the role of Ito in pVT initiation. Computer modeling showed that EADs occur preferentially in the RV because of the larger conductance of the slow-inactivating component of Ito, which repolarizes the membrane potential sufficiently rapidly to allow reactivation of ICa,L before IKr has had sufficient time to activate. CONCLUSIONS: Ito heterogeneity creates both triggers and an arrhythmogenic substrate in LQT1. In the absence of IKs, Ito interactions with ICa,L and IKr promote EADs in the RV while prolonging action potential duration in the left ventricle. This heterogeneity of action potential enhances dispersion of refractoriness and facilitates conduction blocks that initiate pVTs.

The wide utility of rabbits as models of human diseases.

Studies using the European rabbit Oryctolagus cuniculus contributed to elucidating numerous fundamental aspects of antibody structure and diversification mechanisms and continue to be valuable for the development and testing of therapeutic humanized polyclonal and monoclonal antibodies. Additionally, during the last two decades, the use of the European rabbit as an animal model has been increasingly extended to many human diseases. This review documents the continuing wide utility of the rabbit as a reliable disease model for development of therapeutics and vaccines and studies of the cellular and molecular mechanisms underlying many human diseases. Examples include syphilis, tuberculosis, HIV-AIDS, acute hepatic failure and diseases caused by noroviruses, ocular herpes, and papillomaviruses. The use of rabbits for vaccine development studies, which began with Louis Pasteur's rabies vaccine in 1881, continues today with targets that include the potentially blinding HSV-1 virus infection and HIV-AIDS. Additionally, two highly fatal viral diseases, rabbit hemorrhagic disease and myxomatosis, affect the European rabbit and provide unique models to understand co-evolution between a vertebrate host and viral pathogens.

Bio-synthesis of palladium nanocubes and their electrocatalytic properties.

The bio-synthesis of palladium nanocubes (PdNCs) was realised using pine needle extract as the reducing agent and cetyl trimethyl ammonium bromide as the capping agent. As an eco-friendly and readily available biomass, pine needle extract avoided the use of highly polluting chemical reducing agents. The growth process of PdNCs was analysed using ultraviolet-vis and Fourier transform infrared spectroscopy. Flavonoids, esters, terpenoids and polyhydric alcohols, which contain reductive groups, were mainly responsible for the transition of Pd2+ ions to PdNCs. The morphology and structure of PdNCs were characterised using transmission electron microscopy (TEM), high-resolution TEM, selected area electron diffraction and X-ray diffraction. It was indicated that the as-prepared PdNCs displayed a relatively high purity and good crystallinity with a face-centred cubic structure and exhibited sizes ranging from 6.11 to 29.51 nm with an average particle size of 11.18 nm. In the methanol electro-oxidation reaction, the PdNCs enclosed by {100} facets exhibited superior electro-catalytic activity to commercial Pd/C, which was rarely reported in other bio-synthesis processes for Pd catalysts. Meanwhile, the PdNCs showed excellent anti-poisoning ability and long-term stability. This study reveals the possibility of preparing shape-controlled PdNCs with a specific structure and excellent electro-catalytic activity.