Real-Time analysis of exosome secretion of single cells with single molecule imaging

The exosome-mediated response can promote or restrain the diseases by regulating the intracellular pathways, making the exosome become an effective marker for diagnosis and therapeutic control at the single-cell level. However, real-time analysis is hard to be achieved with traditional approaches because the exosomes usually need to be enriched by ultracentrifugation for a measurable signal-to-noise ratio. Recently developed label-free single-molecule imaging approaches may become an real-time quantitative tool for the analysis of single exosomes and related secretion behaviors of single living cells owing to their extreme sensitivity.     

Stress field and damage evolution in C/SiC woven composites: Image-based finite element analysis and in situ X-ray computed tomography tests

The construction and examination of meso-structural finite element models of a Chemical-Vapor-Infiltrated (CVI) C/SiC composite is carried out based on X-ray microtomography digital images (IB-FEM). The accurate meso-structural features of the C/SiC composites, which are consisted of carbon fiber tows and CVI-SiC matrix, in particular the cavity defects, are reconstructed. With the IB-FEM, the damage evolution and fracture behaviors of the C/SiC composite are investigated. At the same time, an in situ tensile test is applied to the C/SiC composite under a CT real-time quantitative imaging system, aiming to investigate the damage and failure features of the material as well as to verify the IB-FEM. The IB-FEM results indicate that material damage initially occur at the defects, followed by propagating toward the fiber-tow/SiC-matrix interfaces, ultimately, combined into macro-cracks, which is in good agreement with the in situ CT experiment results.     

A Bio-Conjugated Fullerene as a Subcellular-Targeted and Multifaceted Phototheranostic Agent

Fullerenes are candidates for theranostic applications because of their high photodynamic activity and intrinsic multimodal imaging contrast. However, fullerenes suffer from low solubility in aqueous media, poor biocompatibility, cell toxicity, and a tendency to aggregate. C₇₀@lysozyme is introduced herein as a novel bioconjugate that is harmless to a cellular environment, yet is also photoactive and has excellent optical and optoacoustic contrast for tracking cellular uptake and intracellular localization. The formation, water-solubility, photoactivity, and unperturbed structure of C₇₀@lysozyme are confirmed using UV-visible and 2D ¹H, ¹⁵N NMR spectroscopy. The excellent imaging contrast of C₇₀@lysozyme in optoacoustic and third harmonic generation microscopy is exploited to monitor its uptake in HeLa cells and lysosomal trafficking. Last, the photoactivity of C₇₀@lysozyme and its ability to initiate cell death by means of singlet oxygen (¹O₂) production upon exposure to low levels of white light irradiation is demonstrated. This study introduces C₇₀@lysozyme and other fullerene-protein conjugates as potential candidates for theranostic applications.     

Organic Semiconducting Luminophores for Near-Infrared Afterglow,Chemiluminescence, and Bioluminescence Imaging

Optical imaging has played a pivotal role in deciphering in vivo bioinformatics but is limited by shallow penetration depth and poor imaging performance owing to interfering tissue autofluorescence induced by concurrent photoexcitation. The emergence of near-infrared (NIR) self-luminescence imaging independent of real-time irradiation has timely addressed these problems. There are two main kinds of self-luminescent agents, namely inorganic and organic luminophores. Inorganic luminophores usually suffer from long-term biotoxicity concerns resulting from potential heavy-metal ions leakage and nonbiodegradability, which hinders their further translational application. In contrast, organic luminophores, especially organic semiconducting luminophores (OSLs) with good biodegradable potential, tunable design, and outstanding optical properties, are preferred in biological applications. This review summarizes the recent progress of OSLs used in NIR afterglow, chemiluminescence, and bioluminescence imaging. Molecular manipulation and nanoengineering approaches of OSLs are discussed, with emphasis on strategies that can extend the emission wavelength from visible to NIR range and amplify luminescence signals. This review concludes with a discussion of current challenges and possible solutions of OSLs in the self-luminescence field.     

Enhancement of glass-ceramic performance by TiO2 doping: In vitro cell viability,proliferation, and differentiation

A new TiO₂-containing bioactive glass and glass-ceramics based on 50SiO₂-(45-X)CaO-(XTiO₂)-5P₂O₅ system was designed using a sol–gel technique (where X = 5, 7.5 and 10 wt %). The roles of the crystallization behavior and physicochemical characteristics of the designed glass and glass-ceramics which were played in the introduction of TiO₂ substitutions were investigated. Moreover, cell proliferation and differentiation were evaluated against human osteosarcoma cells (Saos-2). The TiO₂/CaO replacements led to the formation of a stronger glass structure and thus increased thermal parameters and the chemical stabilization of the designed materials. The FTIR data confirmed the existence of Ti within the glass and glass-ceramics samples, and no remarkable effect on their chemical integrity was observed. The XRD patterns indicated that calcium-containing minerals, including Ca₂SiO₄,Ca₃(PO₄)₂, Ca(Ti,Si)O₅, CaTiSiO₅, and Ca₁₅(PO₄)₂·(SiO₄)₆ phases were developed as a role of structure/texture under the applied heat-treatment. The results of the cytotoxicity test proved that a safe sample dose is 12–50 μg/ml, at which cell viability is ≥ 85%. The cell differentiation determined by ALP test proved the superiority of glass-ceramics compared with their native glasses. Therefore, the obtained materials could be safely used as novel biocompatible materials for the regeneration of bone tissue.     

Preclinical Evaluation of 99mTc-ZHER2:41071, a Second-Generation Affibody-Based HER2-Visualizing Imaging Probe with a Low Renal Uptake

Radionuclide imaging of HER2 expression in tumours may enable stratification of patients with breast, ovarian, and gastroesophageal cancers for HER2-targeting therapies. A first-generation HER2-binding affibody molecule [^99mTc]Tc-ZHER2:V2 demonstrated favorable imaging properties in preclinical studies. Thereafter, the affibody scaffold has been extensively modified, which increased its melting point, improved storage stability, and increased hydrophilicity of the surface. In this study, a second-generation affibody molecule (designated ZHER2:41071) with a new improved scaffold has been prepared and characterized. HER2-binding, biodistribution, and tumour-targeting properties of [^99mTc]Tc-labelled ZHER2:41071 were investigated. These properties were compared with properties of the first-generation affibody molecules, [^99mTc]Tc-ZHER2:V2 and [^99mTc]Tc-ZHER2:2395. [^99mTc]Tc-ZHER2:41071 bound specifically to HER2 expressing cells with an affinity of 58 ± 2 pM. The renal uptake for [^99mTc]Tc-ZHER2:41071 and [^99mTc]Tc-ZHER2:V2 was 25–30 fold lower when compared with [^99mTc]Tc-ZHER2:2395. The uptake in tumour and kidney for [^99mTc]Tc-ZHER2:41071 and [^99mTc]Tc-ZHER2:V2 in SKOV-3 xenografts was similar. In conclusion, an extensive re-engineering of the scaffold did not compromise imaging properties of the affibody molecule labelled with ^99mTc using a GGGC chelator. The new probe, [^99mTc]Tc-ZHER2:41071 provided the best tumour-to-blood ratio compared to HER2-imaging probes for single photon emission computed tomography (SPECT) described in the literature so far. [^99mTc]Tc-ZHER2:41071 is a promising candidate for further clinical translation studies.     

Display illumination with modulated directional backlight

Illumination is essential for modern life as colorful world is perceived by human visionary system. Display technology has been developing rapidly in recent decades, and the basic principle is related to the way that the image is illuminated and light is emanated. Traditional illumination is provided by different types of light sources, and the display image is visible in large viewing space until the emanating light decays to zero. This work proposes and demonstrates a novel illumination scheme for a display in which the displaying images are visible only in specific spatial regions. The directional backlight ensures the image propagating to specific direction while imaging visibility can be controlled to terminate abruptly at certain distance from the display screen while exerting no influence to nearby regions. The working principle for such an illumination scheme is the use of the modulated coherent directional backlight through an axicon lens. It is shown that the illumination scheme can robustly deliver carried image information to the designated viewing region. This new illumination scheme has many advantages over conventional illumination, including its usage for personal display, very lower energy consumption, as well as minimizing light hazard pollution.     

Enhanced mechanical properties of porous titanium implants via in-situ synthesized titanium carbide in lamellar pore walls

Directional lamellar porous titanium scaffolds are widely used as bone implant bearing materials because of their anisotropic pore structure. Their mechanical properties can be effectively improved by enhancing the strength of pore walls through the introduction of ceramics. In this work, porous titanium implants were prepared by freeze casting combined with TiH₂ decomposition. The graphene was introduced into the pore walls of porous titanium, which could transform into titanium carbide (TiC) in situ upon sintering. TiC was evenly distributed in the lamellar pore walls, and the interface was well bonded. The compression strength of the fabricated implants was up to 389.94 MPa when the graphene content was 3 wt%, which was 377.8% times as high as the porous titanium. The crack propagation was resisted by TiC because of the “pinning” effect on the pore wall. Some of TiC were pulled out from the matrix, and others were fractured. The strength of the fabricated implants was improved significantly by the large consumption of fracture energy. Also, fabricated porous titanium implants with TiC are suitable for bone implantation.     

Retinal microaneurysms detection using adversarial pre-training with unlabeled multimodal images

The detection of retinal microaneurysms is crucial for the early detection of important diseases such as diabetic retinopathy. However, the detection of these lesions in retinography, the most widely available retinal imaging modality, remains a very challenging task. This is mainly due to the tiny size and low contrast of the microaneurysms in the images. Consequently, the automated detection of microaneurysms usually relies on extensive ad-hoc processing. In this regard, although microaneurysms can be more easily detected using fluorescein angiography, this alternative imaging modality is invasive and not adequate for regular preventive screening.In this work, we propose a novel deep learning methodology that takes advantage of unlabeled multimodal image pairs for improving the detection of microaneurysms in retinography. In particular, we propose a novel adversarial multimodal pre-training consisting in the prediction of fluorescein angiography from retinography using generative adversarial networks. This pre-training allows learning about the retina and the microaneurysms without any manually annotated data. Additionally, we also propose to approach the microaneurysms detection as a heatmap regression, which allows an efficient detection and precise localization of multiple microaneurysms. To validate and analyze the proposed methodology, we perform an exhaustive experimentation on different public datasets. Additionally, we provide relevant comparisons against different state-of-the-art approaches. The results show a satisfactory performance of the proposal, achieving an Average Precision of 64.90%, 31.36%, and 33.55% in the E-Ophtha, ROC, and DDR public datasets. Overall, the proposed approach outperforms existing deep learning alternatives while providing a more straightforward detection method that can be effectively applied to raw unprocessed retinal images.     

Facile fabrication of MOF-decorated nickel iron foam for highly efficient oxygen evolution

Metal-organic frameworks (MOFs) have emerged as efficient electrocatalysts due to the features of high specific surface area, rich pore structure and diversified composition. It is still challenging to synthesize self-supporting MOF-based catalysts using simple and low-cost fabrication methods. Herein, we successfully fabricated Ni-doped MIL-53(Fe) supported on nickel-iron foam (Ni-MIL-53(Fe)/NFF) as efficient electrocatalyst. A facile two-step solvothermal method without adding any metal salts was used, which can simplify the fabrication process and reduce the experimental cost. In the fabrication process, the bimetallic Ni-MIL-53(Fe)/NFF was in situ converted from an intermediate NiFe₂O₄/NFF. The obtained material exhibits outstanding electrocatalytic oxygen evolution performance with a low overpotential of 248 mV at 50 mA cm^?2, and a small Tafel slope of 46.4 mV dec^?1. This work sheds light on the simple and efficient preparation of bimetallic MOF-based material, which is promising in electrocatalysts.