Viscosity & SO2-sensitive dual colorimetric effect fluorescent sensor enabled imaging detection within plant onion and biological system.

The biological microenvironment includes important parameters such as viscosity, polarity, temperature, oxygen content and pH. In particular, abnormal cell viscosity is associated with the development of major diseases. Sulphur dioxide (SO2) serves not only as an essential atmospheric pollutant but also an influential signalling molecule in biological cells, predisposing individuals to increased respiratory disease. In this work, we designed and synthesized a novel fluorescent probe CouCN-V&S with dual response to micro environmental viscosity and SO2. The probe monitored viscosity and SO2 separately through dual emission channels with a difference of 135 nm. The probe responded sensitively to SO2 (<1s) and exhibited satisfactory immunity to interference and pH stability. The probe was successfully applied to imaging cellular, intra-zebrafish viscosity and SO2 changes. Interestingly, we took onion epidermal cells as model and explored the capability of probe CouCN-V&S to image SO2 in plant cells for the first time.

Effect of different substituents on the fluorescence properties of precursors of synthetic GFP analogues and a polarity-sensitive lipid droplet probe with AIE properties for imaging cells and zebrafish.

The green fluorescent protein (GFP) is a purely natural specialty protein that has been widely used to design synthetic fluorescent probes. In the present work we designed and synthesized a series of fluorescent compounds akin to GFP precursors by a one-step method, and investigated the luminescence properties of the fluorescent compounds by varying the substituents. We presented the first systematic summary of the photophysical data including extinction coefficients and fluorescence quantum yields for this class of fluorescent dyes. We also carried out density functional theory (DFT) calculations for these dyes to investigate the effect of electronic effects due to different substituents. These studied optical properties may provide a reference for later probe design. More interestingly, we have developed a polarity-sensitive lipid droplet probe T-LD with AIE properties on this basis. The probe exhibited not only favorable pH stability and kinetic stability in terms of optical properties, but also solvent discolouration and polarity-sensitive properties, and was able to label intracellular lipid droplets. We successfully applied the probe for intracellular lipid droplet level monitoring and zebrafish imaging.

Viscosity-Sensitive Solvatochromic Fluorescent Probes for Lipid Droplets Staining.

Lipid droplets (LDs) are simple intracellular storage sites for neutral lipids and exhibit important impact on many physiological processes. For example, the changes in the polar microenvironment inside LDs could affect physiological processes, such as lipid metabolism and storage, protein degradation, signal transduction, and enzyme catalysis. Herein, a new fluorescent chemo-sensor (Couoxo-LD) was formulated by our molecular design strategy. The probe could be applied to effectively label intracellular lipid droplets. Intriguingly, Couoxo-LD demonstrated positive sensitivity to both polarity and viscosity, which might be attributed to its D-π-A structure and the twisted rotational behavior of the carbon-carbon double bond (TICT). Additionally, Couoxo-LD was successfully implemented in cellular imaging due to its excellent selectivity, pH stability, and low biotoxicity. In HeLa cells, the co-localization curve between Couoxo-LD and commercial lipid droplet dyes overlapped at 0.93. The results indicated that the probe could selectively sense LDs in HeLa cells. Meanwhile, Couoxo-LD can be applied for in vivo imaging of zebrafish.

A novel and stable fluorescent probe for tracking Hg2+ with large Stokes shift and its application in cell imaging.

Giving the fact that mercury ions (Hg2+) is highly toxic, migratory and bioaccumulative and even very small amounts of mercury can cause serious damage to health, resulting in many diseases, such as abdominal pain, renal failure, nervous system damage. The content of mercury in drinking water quality standard of our country has been strictly limited. Therefore, it is of good research interest to develop a stable fluorescent probe capable of detecting the presence of mercury in biological cells. In this study, a novel fluorescent probe based on isophoronitriles scaffold, DNC-Hg, was designed and synthesized for monitoring mercury ion in living HeLa cells. The good properties of the probe may be attributed to the unique strong electron-absorbing group in the structural design, the good conjugation effect, and the mature Hg2+ recognition site. The probe exhibited good selectivity and stability, large Stokes shift(174 nm) and low cytotoxicity. Furthermore, this stable probe DNC-Hg could be used for cellular imaging.

A collagen hydrogel loaded with HDAC7-derived peptide promotes the regeneration of infarcted myocardium with functional improvement in a rodent model.

Myocardial infarction (MI) leads to the loss of cardiomyocytes, left ventricle (LV) dilation, and cardiac dysfunction, eventually developing into heart failure. Most of the strategies for MI therapy require biomaterials that can support tissue regeneration. In this study, we hypothesized that the extracellular matrix (ECM)-derived collagen I hydrogel loaded with histone deacetylase 7 (HDAC7)-derived-phosphorylated 7-amino-acid peptide (7Ap) could restrain LV remodeling and improve cardiac function after MI. An MI model was established by ligation of the left anterior descending coronary artery (LAD) of C57/B6 mice. The 7Ap-loaded collagen I hydrogel was intramyocardially injected to the infarcted region of the LV wall of the heart. After local delivery, the 7Ap-collagen increased neo-microvessel formation, enhanced stem cell antigen-1 positive (Sca-1+) stem cell recruitment and differentiation, decreased cellular apoptosis, and promoted cardiomyocyte cycle progression. Furthermore, the 7Ap-collagen restricted the fibrosis of the LV wall, reduced the infarct wall thinning, and improved cardiac performance significantly at 2 weeks post-MI. These results highlight the promising implication of 7Ap-collagen as a novel candidate for MI therapy. STATEMENT OF SIGNIFICANCE: The mammalian myocardium has a limited regenerative capability following myocardial infarction (MI). MI leads to extensive loss of cardiomyocytes, thus culminating in adverse cardiac remodeling and congestive heart failure. In situ tissue regeneration through endogenous cell mobilization has great potential for tissue regeneration. A 7-amino-acid-peptide (7A) domain encoded by a short open-reading frame (sORF) of the HDAC7 gene. The phosphorylated from of 7A (7Ap) has been reported to promote in situ tissue repair via the mobilization and recruitment of endogenous stem cell antigen-1 positive (Sca-l+) stem cells. In this study, 7Ap was shown to improve H9C2 cell survival, in vitro. In vivo investigations in a mouse MI model demonstrated that intra-myocardial delivery of 7Ap-loaded collagen hydrogel promoted neovascularization, stimulated Sca-l+ stem cell recruitment and differentiation, reduced cardiomyocyte apoptosis and promoted cell cycle progression. As a result, treated infarcted hearts had increased wall thickness, had improved heart function and exhibited attenuation of adverse cardiac remodeling, observed for up to 2 weeks. Overall, these results highlighted the positive impact of implanting 7Ap-collagen as a novel constituent for MI repair.

Composite Hydrogel Modified by IGF-1C Domain Improves Stem Cell Therapy for Limb Ischemia.

Stem cell treatment for critical limb ischemia yields a limited therapeutic effect due to cell loss and dysfunction caused by local ischemic environment. Biomimetic scaffolds emerge as ideal cell delivery vehicles for regulating cell fate via mimicking the components of stem cell niche. Herein, we prepared a bioactive hydrogel by mixing chitosan and hyaluronic acid that is immobilized with C domain peptide of insulin-like growth factor 1 (IGF-1C) and examined whether this hydrogel could augment stem cell survival and therapeutic potential. Our results showed that IGF-1C-modified hydrogel increased in vitro viability and proangiogenic activity of adipose-derived stromal cells (ADSCs). Moreover, cotransplantation of hydrogel and ADSCs into ischemic hind limbs of mice effectively ameliorated blood perfusion and muscle regeneration, leading to superior limb salvage. These therapeutic effects can be ascribed to improved ADSC retention, angiopoientin-1 secretion, and neovascularization, as well as reduced inflammatory cell infiltration. Additionally, hydrogel enhanced antifibrotic activity of ADSCs, as evidenced by decreased collagen accumulation at late stage. Together, our findings indicate that composite hydrogel modified by IGF-1C could promote survival and proangiogenic capacity of ADSCs and thereby represents a feasible option for cell-based treatment for critical limb ischemia.

Finite Difference Micromagnetic Solvers with the Object Oriented MicroMagnetic Framework (OOMMF) on Graphics Processing Units.

A micromagnetic solver using the Finite Difference method on a Graphics Processing Unit (GPU) and its integration with the Object Oriented MicroMagnetic Framework (OOMMF) are presented. Two approaches for computing the magnetostatic field accelerated by the Fast Fourier Transform (FFT) are implemented. The first approach, referred to as the tensor approach, is based on the tensor spatial convolution to directly compute the magnetostatic field from magnetic moments. The second approach, referred to as the scalar potential approach, uses differential operator evaluation through finite differences (divergence for magnetic charge and gradient for magnetostatic field) and spatial convolution for magnetic scalar potential. Comparisons of implementation details, speed, memory consumption and accuracy are provided. The GPU implementation of OOMMF shows up to 32x GPU-CPU speed-up.