Dear Editor, Biomacromolecules aggregate to form membraneless organelles(MLOs)via phase separation has been observed in a variety of physiological processes over the last decade.1 However,the molecular basis of biomacromolecule phase separation in cells and assembly modes of this process remain largely unknown due to a lack of available experimental methods.The dynamics of different MLOs vary widely.For example,in the nucleus of eukaryotic cells,nuclear speckles have been shown to form membraneless organelles by phase separation,and it is mainly involved in the highly dynamic biological process of pre-mRNA splicing.2 In contrast,the structure of heterochromatin regions is relatively stable.3 In this study,we investigated whether heterochromatin protein HP1α and nuclear speckle protein SRSF2,two classical phase separation proteins with different dynamics,share the same basic unit and similar assembly mode during the formation of MLOs.

A cross-linked waterborne polyurethane (CPTMGPU) with long-term stability was developed from poly(ethylene glycol) (PEG), polyoxytetramethylene glycol (PTMG), isophorone diisocyanate (IPDI), l-lysine, and its derivative diamine consisting of gemini quaternary ammonium salt (GQAS), using ethylene glycol diglycidyl ether (EGDE) as a cross-linker. Weight loss test, X-ray photoelectron spectroscopy (XPS) measurements, and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) were performed to prove the surface structure and stability of these CPTMGPU films. Furthermore, the GQAS-bearing CPTMGPUs show repeatable contact-active antibacterial efficacy against both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) bacteria and do not show any inhibition effect against fibroblasts in vitro. After subcutaneous implantation in rats, the CPTMGPU films manifest good biocompatibility in vivo, despite the presence of a typical foreign body reaction toward surrounding tissues and mild systematic inflammation reaction that could be eliminated after a short implantation period, as demonstrated by histology and immunohistochemistry combined with interleukin (IL)-1β, IL-4, IL-6, IL-10, and TNF-α analysis though enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (qRT-PCR). Therefore, these cross-linked waterborne polyurethanes hold great promise for antibacterial applications in vivo.

Novel antibacterial waterborne polyurethanes based on gemini quaternary ammonium salt with good biodegradable and biocompatible properties.

Contact-active antibacterial surfaces play a vital role in preventing bacterial contamination of artificial surfaces. In the past, numerous researches have been focused on antibacterial surfaces comprising of antifouling upper-layer and antibacterial sub-layer. In this work, we demonstrate a reversed surface structure which integrate antibacterial upper-layer and antifouling sub-layer. These surfaces are prepared by simply casting gemini quaternary ammonium salt waterborne polyurethanes (GWPU) and their blends. Due to the high interfacial energy of gemini quaternary ammonium salt (GQAS), chain segments containing GQAS can accumulate at polymer/air interface to form an antibacterial upper-layer spontaneously during the film formation. Meanwhile, the soft segments composed of polyethylene glycol (PEG) formed the antifouling sub-layer. Our findings indicate that the combination of antibacterial upper-layer and antifouling sub-layer endow these surfaces strong, long-lasting antifouling and contact-active antibacterial properties, with a more than 99.99% killing efficiency against both gram-positive and gram-negative bacteria attached to them.

Images of pharmacokinetic parameters in dynamic fluorescence molecular tomography (FMT) have the potential to provide quantitative physiological information for biological studies and drug development. However, images obtained with conventional indirect methods suffer from low signal-to-noise ratio because of failure in efficiently modeling the measurement noise. Besides, FMT suffers from low spatial resolution due to its ill-posed nature, which further reduces the image quality. In this letter, we present a direct method with structural priors for imaging pharmacokinetic parameters, which uses a nonlinear objective function to efficiently model the measurement noise and utilizes the structural priors to mitigate the ill-posedness of FMT. The results of numerical simulations and in vivo mouse experiments demonstrate that the proposed method leads to significant improvements in the image quality.

Novel non-releasing antibacterial poly(styrene-acrylate)/waterborne polyurethane composites containing gemini quaternary ammonium salt were designed and preparedviaa facile blending strategy.

Dynamic fluorescence molecular tomography (FMT) is an attractive imaging technique for three-dimensionally resolving the metabolic process of fluorescent biomarkers in small animal. When combined with compartmental modeling, dynamic FMT can be used to obtain parametric images which can provide quantitative pharmacokinetic information for drug development and metabolic research. However, the computational burden of dynamic FMT is extremely huge due to its large data sets arising from the long measurement process and the densely sampling device. In this work, we propose to accelerate the reconstruction process of dynamic FMT based on principal component analysis (PCA). Taking advantage of the compression property of PCA, the dimension of the sub weight matrix used for solving the inverse problem is reduced by retaining only a few principal components which can retain most of the effective information of the sub weight matrix. Therefore, the reconstruction process of dynamic FMT can be accelerated by solving the smaller scale inverse problem. Numerical simulation and mouse experiment are performed to validate the performance of the proposed method. Results show that the proposed method can greatly accelerate the reconstruction of parametric images in dynamic FMT almost without degradation in image quality.

It is a challenging problem to resolve and identify drug (or non-specific fluorophore) distribution throughout the whole body of small animals in vivo. In this article, an algorithm of unmixing multispectral fluorescence tomography (MFT) images based on independent component analysis (ICA) is proposed to solve this problem. ICA is used to unmix the data matrix assembled by the reconstruction results from MFT. Then the independent components (ICs) that represent spatial structures and the corresponding spectrum courses (SCs) which are associated with spectral variations can be obtained. By combining the ICs with SCs, the recovered MFT images can be generated and fluorophore concentration can be calculated. Simulation studies, phantom experiments and animal experiments with different concentration contrasts and spectrum combinations are performed to test the performance of the proposed algorithm. Results demonstrate that the proposed algorithm can not only provide the spatial information of fluorophores, but also recover the actual reconstruction of MFT images.

Subsurface fluorescence molecular tomography (FMT) is an emerging technique determining fluorescence distribution by tomographic means in reflectance geometry. However, due to the highly diffusive nature of the photon propagation in biological tissues and the influence of nearer source-detector separations, stand-alone subsurface FMT could not accurately reflect the fluorophore distributions. To overcome this drawback, we propose a method to improve the performance of fluorescence imaging by coupling x-ray computed tomography (XCT) and subsurface FMT modalities. A Laplacian-type regularization matrix generated with tissue prior information obtained from XCT images is used to guide the reconstruction of fluorophore distribution. Reconstruction results of both simulation and phantom studies showed that significant improvements in localization and demarcation of fluorescent targets can be obtained with the proposed method compared to the reconstruction method without structural prior information.

Dual modality molecular imaging can capture concurrent molecular events and evaluate therapeutic efficacy from uniquely different perspectives based on different molecular targets. In this work, dual modality tomographic imaging, (18) F-fluorodeoxyglucose based positron emission tomography and subsurface fluorescence molecular tomography ([(18) F]FDG-PET/subsurface FMT), is proposed to monitor tumor response to cisplatin on a mouse xenograft model in vivo. One mouse was administered with cisplatin (1.0 mg/kg) by intraperitoneal injection once every day for 14 days, and another mouse was administered with saline to serve as the control. Dual modality [(18) F]FDG-PET/subsurface FMT imaging was conducted on days 0, 2, 5, 9, 15, and 22. In vivo imaging and quantitative analysis demonstrated the feasibility of [(18) F]FDG-PET/subsurface FMT imaging in tracking the changes of [(18) F]FDG tumor uptake and amount of red fluorescent protein (RFP) synthesized by tumor cells in the same mouse simultaneously. Dual modality [(18) F]FDG-PET/subsurface FMT imaging may thus provide a powerful tool for better understanding disease progress and treatment evaluation from different perspectives.

In conventional fluorescence molecular tomography, the distribution of fluorescent contrast agents is reconstructed with the assumption of constant concentration during data acquisition for each image frame. However, the concentration of fluorescent contrast target is usually time-varying in experiments or in-vivo studies. In this case, the reconstruction methods cannot be directly applied to the fluorescence measurements without considering the time-varying effects of concentration. We propose a modified forward model by dividing the fluorescence yield distribution into two parts: one is a constant representing the spatial distribution of the fluorescent target and the other is an impact factor representing the effects of the concentration change and other possible factors. By extracting spatial distribution information from the reconstruction result, the location and volume of the fluorescent target can be obtained accurately. Both simulation and phantom experiments are carried out and the results indicate that, by using the modified forward model, the quality of reconstruction could be significantly improved in terms of accurate localization and strong anti-noise ability.

Multispectral excitation-resolved fluorescence tomography (MEFT) uses excitation light of different wavelengths to illuminate the fluorophores and obtains the reconstruction image frame which is fluorescence yield at each corresponding wavelength. For structures containing fluorophores of different concentrations, fluorescence yields show different variation trends with the excitation spectrum. In this study, principal component analysis (PCA) is used to analyze the MEFT reconstructed image frames. By taking advantage of the different variation trends of fluorescence yields, PCA can provide a set of principal components (PCs) in which structures containing different concentrations of fluorophores are shown separately. Simulations and experiments are both performed to test the performance of the proposed algorithm. The results suggest that the location and structure of fluorophores with different concentrations can be obtained and the contrast of fluorophores can be improved further by using this algorithm.