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In this paper, we show that gadolinium-loaded synthetic melanin nanoparticles (Gd(III)-SMNPs) exhibit up to a 40-fold enhanced photoacoustic signal intensity relative to synthetic melanin alone and higher than other metal-chelated SMNPs. This property makes these materials useful as dual labeling agents because Gd(III)-SMNPs also behave as magnetic resonance imaging (MRI) contrast agents. As a proof-of-concept, we used these nanoparticles to label human mesenchymal stem cells. Cellular uptake was confirmed with bright-field optical and transmission electron microscopy. The Gd(III)-SMNP-labeled stem cells continued to express the stem cell surface markers CD73, CD90, and CD105 and proliferate. The labeled stem cells were subsequently injected intramyocardially in mice, and the tissue was observed by photoacoustic and MR imaging. We found that the photoacoustic signal increased as the cell number increased (R(2) = 0.96), indicating that such an approach could be employed to discriminate between stem cell populations with a limit of detection of 2.3 × 10(4) cells in in vitro tests. This multimodal photoacoustic/MRI approach combines the excellent temporal resolution of photoacoustics with the anatomic resolution of MRI.

Glutaminase of Bacillus amyloliquefaciens has been used to synthesize the immunomodulatory γ‐D‐glutamyl‐L‐tryptophan (γ‐D‐Glu‐L‐Trp) and the kokumi‐active γ‐D‐glutamyl peptides. The optimum yield of γ‐D‐Glu‐L‐Trp was 55.76 mM in corresponding to a minimum yield of by‐product (γ‐D‐Glu‐γ‐D‐Glu‐L‐Trp) in the presence of 75 mM D‐Gln and 100 mM L‐Trp. The glutaminase has a low Km values for the donors (D‐Gln and L‐Gln:5.53 and 0.98 mM), but high ones for the acceptors (L‐Trp, L‐Phe, L‐Met, L‐Val and γ‐[D‐Glu]( n =1,2,3)‐L‐Val/L‐Phe/L‐Met, ranging from 32.51 to 193.05 mM). The highest Km value appearing when n = 2 (γ‐[D‐Glu]( n =0,1,2)‐L‐Val/L‐Phe/L‐Met) suggested the rising difficulty for synthesis when the number of donor increases in the reaction mixtures. The γ‐[D‐Glu]( n =1,2,3)‐L‐Val/L‐Phe/L‐Met at 5 mM can impart the blank chicken broth an enhancing monthfulness, thickness, and umaminess taste., Glutaminase of Bacillus amyloliquefaciens has been used to synthesize the immunomodulatory γ‐D‐glutamyl‐L‐tryptophan (γ‐D‐Glu‐L‐Trp) and the kokumi‐active γ‐D‐glutamyl peptides. The optimum yield of γ‐D‐Glu‐L‐Trp was 55.76 mM in corresponding to a minimum yield of byproduct (γ‐D‐Glu‐γ‐D‐Glu‐L‐Trp) in the presence of 75 mM D‐Gln and 100 mM L‐Trp. The glutaminase has a low Km values for the donors (D‐Gln and L‐Gln:5.53 and 0.98 mM), but high ones for the acceptors (L‐Trp, L‐Phe, L‐Met, L‐Val and γ‐[D‐Glu](n = 1,2,3)‐L‐Val/Phe/Met, ranging from 32.51 to 193.05 mM). The highest Km value appearing when n=2 (γ‐[D‐Glu](n = 0,1,2)‐L‐Val/Phe/Met) suggested the rising difficulty for synthesis when the number of donor increases in the reaction mixtures. The γ‐[D‐Glu](n = 1,2,3)‐L‐Val/Phe/Met at 5 mM can impart the blank chicken broth an enhancing monthfulness, thickness, and umaminess taste.

Glutaminase of Bacillus amyloliquefaciens has been used to synthesize the immunomodulatory γ‐D‐glutamyl‐L‐tryptophan (γ‐D‐Glu‐L‐Trp) and the kokumi‐active γ‐D‐glutamyl peptides. The optimum yield of γ‐D‐Glu‐L‐Trp was 55.76 mM in corresponding to a minimum yield of by‐product (γ‐D‐Glu‐γ‐D‐Glu‐L‐Trp) in the presence of 75 mM D‐Gln and 100 mM L‐Trp. The glutaminase has a low Km values for the donors (D‐Gln and L‐Gln:5.53 and 0.98 mM), but high ones for the acceptors (L‐Trp, L‐Phe, L‐Met, L‐Val and γ‐[D‐Glu](n=1,2,3)‐L‐Val/L‐Phe/L‐Met, ranging from 32.51 to 193.05 mM). The highest Km value appearing when n = 2 (γ‐[D‐Glu](n=0,1,2)‐L‐Val/L‐Phe/L‐Met) suggested the rising difficulty for synthesis when the number of donor increases in the reaction mixtures. The γ‐[D‐Glu](n=1,2,3)‐L‐Val/L‐Phe/L‐Met at 5 mM can impart the blank chicken broth an enhancing monthfulness, thickness, and umaminess taste.

Liquid crystals (LCs) offer the basis of stimuli-responsive materials that can amplify targeted molecular events into macroscopic outputs. However, general and versatile design principles are needed to realize the full potential of these materials. To this end, we report the synthesis of two homopolymers with mesogenic side chains that can be cleaved upon exposure to either H2 O2 (polymer P1) or UV light (polymer P2). Optical measurements reveal that the polymers dissolve in bulk LC and spontaneously assemble at nematic LC-aqueous interfaces to impose a perpendicular orientation on the LCs. Subsequent addition of H2 O2 to the aqueous phase or exposure of the LC to UV was shown to trigger a surface-driven ordering transition to a planar orientation and an accompanying macroscopic optical output. Differences in the dynamics of the response to each stimulus are consistent with sequential processing of P1 at the LC-aqueous interface (H2 O2 ) and simultaneous transformation of P2 within the LC (UV). The versatility of the approach is demonstrated by creating stimuli-responsive LCs as films or microdroplets, and by dissolving mixtures of P1 and P2 into LCs to create LC materials that respond to two stimuli. Overall, our results validate a simple and generalizable approach to the rational design of polymers that can be used to program stimuli-responsiveness into LC materials.

A primary role of melanin in skin is the prevention of UV-induced nuclear DNA damage to human skin cells, where it serves to screen out harmful UV radiation. Melanin is delivered to keratinocytes in the skin after being excreted as melanosomes from melanocytes. Defects in melanin production in humans can cause diseases, many of which currently lack effective treatments due to their genetic origins (e.g., skin cancer, vitiligo, and albinism). The widespread prevalence of melanin-related diseases and an increasing interest in the performance of various polymeric materials related to melanin necessitates novel synthetic routes for preparing melanin-like materials. In this work, we prepared melanin-like nanoparticles (MelNPs) via spontaneous oxidation of dopamine, as biocompatible, synthetic analogues of naturally occurring melanosomes, and investigated their uptake, transport, distribution, and UV-protective capabilities in human keratinocytes. Critically, we demonstrate that MelNPs are endocytosed, undergo perinuclear aggregation, and form a supranuclear cap, or so-called microparasol in human epidermal keratinocytes (HEKa), mimicking the behavior of natural melananosomes in terms of cellular distribution and the fact that they serve to protect the cells from UV damage., In human skin, melanosomes form microscale umbrellas around nuclei of keratinocytes, shielding DNA from UV damage. Herein, entirely synthetic melanin nanoparticles are accepted by human keratinocytes and are used as artificial UV shields.

Pixel reassignment image scanning microscopy (PRISM) is a useful tool to improve the resolution of confocal laser scanning microscopy (CLSM) only equipped with a detector array. However, while it can improve the lateral resolution, it has little effect on the axial resolution. Here, new microscopy has been proposed which combines three-dimension fluorescence emission difference microscopy (3D FED) with PRISM to further improve three-dimension resolution. We call this method three-dimension pixel reassignment fluorescence emission difference microscopy (3D-PRFED). Detailed theoretical analysis and simulation are presented in this paper. Additionally, the performance of lateral and axial resolution improvement of this method has been demonstrated by imaging 100 nm fluorescent beads and nuclear pore complexes samples. Experiment results show that this method in our system can improve lateral resolution by a factor of 1.85 and axial resolution by a factor of 1.48 compared with CLSM.

Singlet lenses are free from precise assembling, aligning, and testing, which are helpful for the development of portable and low-cost microscopes. However, balancing the spectrum dispersion or chromatic aberrations using a singlet lens made of one material is difficult. Here, a novel method combining singlet lens microscopy and computational imaging, which is based on deep learning image-style-transfer algorithms, is proposed to overcome this problem in clinical pathological slide microscopy. In this manuscript, a singlet aspheric lens is used, which has a high cut-off frequency and linear signal properties. Enhanced by a trained deep learning network, it is easy to transfer the monochromatic gray-scale microscopy picture to a colorful microscopy picture, with only one single-shot recording by a monochromatic CMOS image sensor. By experiments, data analysis, and discussions, it is proved that our proposed virtual colorization microscope imaging method is effective for H&E stained tumor tissue slides in singlet microscopy. It is believable that the computational virtual colorization method for singlet microscopes would promote the low-cost and portable singlet microscopy development in medical pathological label staining observing (e.g., H&E staining, Gram staining, and fluorescent labeling) biomedical research.

Amphiphilic triblock copolymers containing Fe(III) -catecholate complexes formulated as spherical- or cylindrical-shaped micellar nanoparticles (SMN and CMN, respectively) are described as new T1-weighted agents with high relaxivity, low cytotoxicity, and long-term stability in biological fluids. Relaxivities of both SMN and CMN exceed those of established gadolinium chelates across a wide range of magnetic field strengths. Interestingly, shape-dependent behavior is observed in terms of the particles' interactions with HeLa cells, with CMN exhibiting enhanced uptake and contrast via magnetic resonance imaging (MRI) compared with SMN. These results suggest that control over soft nanoparticle shape will provide an avenue for optimization of particle-based contrast agents as biodiagnostics. The polycatechol nanoparticles are proposed as suitable for preclinical investigations into their viability as gadolinium-free, safe, and effective imaging agents for MRI contrast enhancement.

This study reports the preparation of a series of gadolinium-polydopamine nanoparticles (GdPD-NPs) with tunable metal loadings. GdPD-NPs are analyzed by nuclear magnetic relaxation dispersion and with a 7-tesla (T) magnetic resonance imaging (MRI) scanner. A relaxivity of 75 and 10.3 mM−1 s−1 at 1.4 and 7 T is observed, respectively. Furthermore, superconducting quantum interference device magnetometry is used to study intraparticle magnetic interactions and determine the GdPD-NPs consist of isolated metal ions even at maximum metal loadings. From these data, it is concluded that the observed high relaxivities arise from a high hydration state of the Gd(III) at the particle surface, fast rate of water exchange, and negligible antiferromagnetic coupling between Gd(III) centers throughout the particles. This study highlights design parameters and a robust synthetic approach that aid in the development of this scaffold for T1-weighted, high relaxivity MRI contrast agents.

In the past decade, numerous species of nanomaterials have been developed for biomedical application, especially cancer therapy. Realizing visualized therapy is highly promising now because of the potential of accurate, localized treatment. In this work, we first synthesized metal nanorattles (MNRs), which utilized porous gold shells to carry multiple MR imaging contrast agents, superparamagnetic iron oxide nanoparticles (SPIONs), inside. A fragile wormpore-like silica layer was manipulated to encapsulate 8 nm oleylamine SPIONs and mediate the in situ growth of porous gold shell, and it was finally etched by alkaline solution to obtain the rattle-type nanostructure. As shown in the results, this nanostructure with unique morphology could absorb near-infrared light, convert to heat to kill cells, and inhibit tumor growth. As a carrier for multiple SPIONs, it also revealed good function for T2-weighted MR imaging in tumor site. Moreover, the rest of the inner space of the gold shell could also introduce potential ability as nanocarriers for other cargos such as chemotherapeutic drugs, which is still under investigation. This metal rattle-type nanocarrier may pave the way for novel platforms for cancer therapy in the future.

We describe a synthetic method for increasing and controlling the iron loading of synthetic melanin nanoparticles and use the resulting materials to perform a systematic quantitative investigation on their structure–property relationship. A comprehensive analysis by magnetometry, electron paramagnetic resonance, and nuclear magnetic relaxation dispersion reveals the complexities of their magnetic behavior and how these intraparticle magnetic interactions manifest in useful material properties such as their performance as MRI contrast agents. This analysis allows predictions of the optimal iron loading through a quantitative modeling of antiferromagnetic coupling that arises from proximal iron ions. This study provides a detailed understanding of this complex class of synthetic biomaterials and gives insight into interactions and structures prevalent in naturally occurring melanins.

Nanotechnology has been widely used in the development of new strategies for drug delivery and cancer therapy. Compared to traditional drug delivery systems, nano-based drug delivery system have greater potential in a variety of areas, such as multiple targeting functionalization, in vivo imaging, combined drug delivery, extended circulation time, and systemic control release. Nano-systems incorporating stimulus-responsive materials have remarkable properties which allow them to bypass biological barriers and achieve targeted intracellular drug delivery. As a result of the active metabolism of tumor cells, the tumor microenvironment (TME) is highly acidic compared to normal tissues. pH-Sensitive nano-systems have now been developed in which drug release is specifically triggered by the acidic tumor environment. Studies have demonstrated that novel pH-sensitive drug delivery systems are capable of improving the efficiency of cancer treatment. A number of these have been translated from bench to clinical application and have been approved by the Food and Drug Administration (FDA) for treatment of various cancerous diseases. Herein, this review mainly focuses on pH-sensitive nano-systems, including advances in drug delivery, mechanisms of drug release, and possible improvements in drug absorption, with the emphasis on recent research in this field. With deeper understanding of the difference between normal and tumor tissues, it might be possible to design ever more promising pH-responsive nano-systems for drug delivery and cancer therapy in the near future.

To mimic the extracellular microenvironment of bone, a bioactive multilayered structure of gelatin/chitosan pair, containing bone morphogenetic protein 2(BMP2) and fibronectin (FN), was constructed onto Ti6Al4V surface via a layer-by-layer assembly technique. The successful fabrication of multilayered structure was confirmed by contact angle measurement, field emission scanning electron microscopy (FE-SEM) and confocal laser scanning microscopy (CLSM), respectively. Bioactive BMP2 released in a sustained manner along with the degradation of multilayered structure. MSCs grown onto the multilayer coated TC4 substrates displayed significantly higher (p < 0.01 or p < 0.05) production levels of alkaline phosphatase (ALP), mineralization and genes expressions of runt related transcription factor 2 (Runx2), osterix, osteocalcin (OC), osteopontin (OPN), ALP and collagen type Ⅰ(ColⅠ) compared to the controls after culture for 7 days and 21 days, respectively. More importantly, MicroCT analysis and histological observations demonstrated that the multilayer coated Ti6Al4V implants in vivo promoted the bone density and new bone formation around them after implantation for 4 weeks and 12 weeks, respectively. The results indicated that Ti6Al4V coated with biofunctional multilayers was beneficial for osteogenesis and integration of implant/bone. The study therefore presents an alternative to fabricate bio-functionalized Ti6Al4V-based implants for potential application in orthopedics field.

The extracellular microenvironment plays a key role in the regulation of cellular behavior. To mimic the natural extracellular microenvironment, TiO(2) nanotube (TNT) arrays as drug nanoreservoirs for loading of bone morphogenetic protein 2 (BMP2) were constructed on titanium substrates and then covered with multilayered coatings of gelatin/chitosan (Gel/Chi) for controlled drug release. The multilayered coatings were constructed via a spin-assisted layer-by-layer assembly technique. The successful fabrication of this system was monitored by field emission scanning electron microscopy, atomic force microscopy, X-ray photoelectron spectroscopy and contact angle measurements. Multilayered coating with Gel/Chi retained the drug bioactivity and release properties, which were revealed by superoxide dismutase activity measurement. In addition, cytoskeleton observation and wound healing assay confirmed that BMP2-loaded and multilayer-coated TNT arrays were able to stimulate motogenic responses of mesenchymal stem cells (MSCs). More importantly, the system demonstrated that it was capable of promoting the osteoblastic differentiation of MSCs. This study may have potential impact on the development of bone implants for enhanced bone osseointegration.