Fractional flow reserve for coronary stenosis assessment derived from fusion of intravascular ultrasound and X-ray angiography.

BACKGROUND: Intravascular ultrasound (IVUS) provides good insight into lumen boundary and plaques; however, it is still difficult to detect functionally significant stenosis from IVUS images for the guidance of coronary percutaneous intervention (PCI). This study aimed to develop a novel method to estimate fractional flow reserve (FFR) value for determining the functional significance of coronary artery disease through the fusion of IVUS and X-ray angiographic images. METHODS: We developed a novel approach to 3D vessel reconstruction by integrating IVUS with X-ray angiographic images. Based on the reconstructed geometry and the inlet flow derived from the thrombolysis in myocardial infarction (TIMI) frame count, a simplified fluid dynamics equation was established to compute the pressure drop and IVUS-derived FFR (AccuFFRivus) was subsequently obtained. To validate the feasibility and performance of this IVUS-based FFR method, we performed AccuFFRivus calculations on 32 coronary vessels with invasive FFR as the reference standard. RESULTS: Great correlation (r=0.86, P<0.001) was observed between AccuFFRivus and FFR. The area under the receiver-operating characteristic curve (AUC) was higher for AccuFFRivus than minimal lumen area (MLA, <4 mm2) and diameter stenosis rate (DS% ≥50%) [0.98 (95% CI: 0.86 to 1.0) vs. 0.78 (95% CI: 0.60 to 0.91) and 0.66 (95% CI: 0.47 to 0.82)]. Bland-Altman plot showed a mean difference value of -0.011 (limits of agreement: -0.156 to 0.134). CONCLUSIONS: AccuFFRivus is a novel method for hybridizing IVUS and X-ray angiographic images to identify functionally significant stenosis with FFR ≤0.80. The good diagnostic performance from the initial validation study demonstrates the potential for clinical utilization of physiologically guided decision-making. Further validation is required in future studies with a large number of cases.

Mechanistic process understanding of the self-assembling behaviour of asymmetric bolaamphiphilic short-peptides and their templating for silica and titania nanomaterials.

Investigation of the self-assembly of peptides is critically important to clarify certain biophysical phenomena, fulfill some biological functions, and construct functional materials. However, it is still a challenge to precisely predict the self-assembled structures of peptides because of their complicated driving forces and various assembling pathways. In this work, to elucidate the effects of noncovalent interactions including hydrogen bonding, molecular geometry, and hydrophobic and electrostatic interactions on the peptide self-assembly, a series of asymmetric bolaamphiphilic short peptides consisting of Ac-EI3K-NH2 (EI3K), Ac-EI4K-NH2 (EI4K), Ac-KI3E-NH2 (KI3E) and Ac-KI4E-NH2 (KI4E) were designed and their self-assembling behaviors at different solution pH values were investigated systematically. The peptides self-assembled into twisted nanofibers under most conditions except for EI4K in a strongly alkaline solution and KI4E under a strongly acidic condition, in which they self-assembled into nanotubes via helical monolayer nanosheet intermediates. In particular, KI4E nanotubes are formed under acidic conditions, and its diameters are ∼500 nm much greater than most of the self-assembled structures from bolaamphiphilic peptides. Moreover, reversible morphological transition between the nanotubes and twisted nanofibers was observed with the change in solution pH. Such tunable self-assembled structures and switchable surface properties of the asymmetric bolaamphiphilic short-peptides allow them to be used as templates to construct advanced materials. Silica and titania nanomaterials faithful to the peptide templates in morphology were prepared at ambient temperature. This work clearly elucidates the effects of noncovalent interactions on the peptide self-assembly and also provides new insights into the design and preparation of complicated inorganic materials from tunable organic templates.

Peptide-mediated porphyrin based hierarchical complexes for light-to-chemical conversion.

We present a new strategy for the biomimetic preparation of integrated photoactive complexes consisting of light harvesting and electron separation/transfer components via the hierarchical assembly of porphyrin and platinum nanoparticles on the surface of short-peptide self-assembled structures. The complexes can catalyze the conversion of visible light energy into chemical energy in the absence of an electron mediator and store it as nicotinamide adenine dinucleotide (NADH). This provides a promising step towards artificial photosystems through precisely controlled interactions of light-capturing agents, electron separators and biomolecules.

Fabrication of Patterned Thermoresponsive Microgel Strips on Cell-Adherent Background and Their Application for Cell Sheet Recovery.

Interfaces between materials and cells play a critical role in cell biomedical applications. Here, a simple, robust, and cost-effective method is developed to fabricate patterned thermoresponsive poly(N-isopropylacrylamide-co-styrene) microgel strips on a polyethyleneimine-precoated, non-thermoresponsive cell-adherent glass coverslip. The aim is to investigate whether cell sheets could be harvested from these cell-adherent surfaces patterned with thermoresponsive strips comprised of the microgels. We hypothesize that if the cell-to-cell interaction is strong enough to retain the whole cell sheet from disintegration, the cell segments growing on the thermoresponsive strips may drag the cell segments growing on the cell-adherent gaps to detach, ending with a whole freestanding and transferable cell sheet. Critical value concerning the width of the thermoresponsive strip and its ratio to the non-thermoresponsive gap may exist for cell sheet recovery from this type of surface pattern. To obtain this critical value, a series of strip patterns with various widths of thermoresponsive strip and non-thermoresponsive gap were prepared using negative microcontact printing technology, with COS7 fibroblast cells being used to test the growth and detachment. The results unraveled that COS7 cells preferentially attached and proliferated on the cell-adherent, non-thermoresponsive gaps to form patterned cell layers and that they subsequently proliferated to cover the microgel strips to form a confluent cell layer. Intact COS7 cell sheets could be recovered when the width of the thermoresponsive strip is no smaller than that of the non-thermoresponsive gap. Other cells such as HeLa, NIH3T3, 293E, and L929 could grow similarly; that is, they showed initial preference to the non-thermoresponsive gaps and then migrated to cover the entire patterned surface. However, it was difficult to detach them as cell sheets due to the weak interactions within the cell layers formed. In contrast, when COS7 and HeLa cells were cultured successively, they formed the cocultured cell layer that could be detached together. These freestanding patterned cell sheets could lead to the development of more elaborate tumor models for drug targeting and interrogation.

Visible and Near-Infrared Dual-Emission Carbogenic Small Molecular Complex with High RNA Selectivity and Renal Clearance for Nucleolus and Tumor Imaging.

Fluorescence imaging requires bioselective, sensitive, nontoxic molecular probes to detect the precise location of lesions for fundamental research and clinical applications. Typical inorganic semiconductor nanomaterials with large sizes (>10 nm) can offer high-quality fluorescence imaging due to their fascinating optical properties but are limited to low selectivity as well as slow clearance pathway. We here report an N- and O-rich carbogenic small molecular complex (SMC, MW < 1000 Da) that exhibits high quantum yield (up to 80%), nucleic acid-binding enhanced excitation-dependent fluorescence (EDF), and a near-infrared (NIR) emission peaked at 850 nm with an ultralarge Stokes shift (∼500 nm). SMCs show strong rRNA affinity, and the resulting EDF enhancement allows multicolor visualization of nucleoli in cells for clear statistics. Furthermore, SMCs can be efficiently accumulated in tumor in vivo after injection into tumor-bearing mice. The NIR emission affords high signal/noise ratio imaging for delineating the true extent of tumor. Importantly, about 80% of injected SMCs can be rapidly excreted from the body in 24 h. No appreciable toxicological responses were observed up to 30 days by hematological, biochemical, and pathological examinations. SMCs have great potential as a promising nucleolus- and tumor-specific agent for medical diagnoses and biomedical research.

An Ultra-High Fluorescence Enhancement and High Throughput Assay for Revealing Expression and Internalization of Chemokine Receptor CXCR4.

Revealing chemokine receptor CXCR4 expression, distribution, and internalization levels in different cancers helps to evaluate cancer progression or prognosis and to set personalized treatment strategy. We here describe a sensitive and high-throughput immunoassay for determining CXCR4 expression and distribution in cancer cells. The assay is accessible to a wide range of users in an ordinary lab only by dip-coating poly(styrene-co-N-isopropylacrylamide) spheres on the glass substrate. The self- assembled spheres form three-dimensional photonic colloidal crystals which enhance the fluorescence of CF647 and Alexa Fluor 647 by a factor of up to 1000. CXCR4 in cells is detected by using the sandwich immunoassay, where the primary antibody recognizes CXCR4 and the secondary antibody is labeled with CF647. With the newly established assay, we quantified the total expression of CXCR4, its distribution on the cell membrane and cytoplasm, and revealed their internalization level upon SDF-1α activation in various cancer cells, even for those with extremely low expression level.

A two-component active targeting theranostic agent based on graphene quantum dots.

Using nanotechnology, therapeutics can be combined with diagnostics for cancer treatment. To do this, a targeting ligand, an imaging contrast agent and an anti-tumour therapeutic agent were the minimum requirements for active targeting nanoassemblies. Here we have developed a novel active targeting theranostic agent, made up of just two components, aptamer AS1411 and graphene quantum dots (GQDs). Each component in our agent plays multiple roles. Confocal microscopy using a 488 nm laser shows that this agent has an excellent capability to label tumour cells selectively. On the therapeutic side, this agent induced a synergistic growth inhibition effect towards cancer cells when irradiated with a near infrared laser of 808 nm. The ultra-small size, good biocompatibility, intrinsic stable fluorescence, and near-infrared response character make GQDs a remarkable constituent to build theranostic agents.