Hypoxic environment of wounds and photosynthesis-based oxygen therapy.

The hypoxic environment is among the most important factors that complicates the healing of chronic wounds, such as venous leg ulcers, pressure injuries and diabetic foot ulcers, which seriously affects the quality of life of patients. Various oxygen supply treatments are used in clinical practice to improve the hypoxic environment at the wound site. However, problems still occur, such as insufficient oxygen supply, short oxygen infusion time and potential biosafety risks. In recent years, artificial photosynthetic systems have become a research hotspot in the fields of materials and energy. Photosynthesis is expected to improve the oxygen level at wound sites and promote wound healing because the method provides a continuous oxygen supply and has good biosafety. In this paper, oxygen treatment methods for wounds are reviewed, and the oxygen supply principle and construction of artificial photosynthesis systems are described. Finally, research progress on the photosynthetic oxygen production system to promote wound healing is summarized.

High-quality coherent ghost imaging of a transmission target.

When the test detector of ghost imaging (GI) is a point-like detector and the detector's transverse size is smaller than the transverse coherence length of the light field at the detection plane, this case is corresponding to coherent GI (CGI) and the imaging result recovered by traditional GI (TGI) reconstruction algorithm is usually bad for a transmission target. Here a CGI scheme of a transmission target is proposed and a corresponding CGI reconstruction algorithm is developed to stably recover the target's image. The validity of the proposed method is verified by both simulation and experiments. Both the simulation and experimental results demonstrate that the target's transmission function can be perfectly reconstructed by CGI. We also show that the imaging quality of CGI with a point-like detector is better than that of TGI with a bucket detector if detection noise exists in the sampling process. Performance comparisons between CGI reconstruction and TGI reconstruction are also discussed.

Disturbance-free single-pixel imaging camera via complementary detection.

We present a technique called single-pixel imaging camera based on complementary detection and optimized encoded modulation (CSPI camera), which can significantly reduce the influence of the disturbance light to single-pixel imaging (SPI). The experiments demonstrates that when the probability of the value "1" for each binary encoded pattern is P=0.5, CSPI camera is still disturbance-free even if the intensity fluctuation of the disturbance light is much larger than the signal's intensity. The reconstruction results of both traditional SPI and differential SPI are also compared. This technique of CSPI camera can dramatically promote real application of single-pixel imaging Lidar.

Far-field super-resolution ghost imaging with a deep neural network constraint.

Ghost imaging (GI) facilitates image acquisition under low-light conditions by single-pixel measurements and thus has great potential in applications in various fields ranging from biomedical imaging to remote sensing. However, GI usually requires a large amount of single-pixel samplings in order to reconstruct a high-resolution image, imposing a practical limit for its applications. Here we propose a far-field super-resolution GI technique that incorporates the physical model for GI image formation into a deep neural network. The resulting hybrid neural network does not need to pre-train on any dataset, and allows the reconstruction of a far-field image with the resolution beyond the diffraction limit. Furthermore, the physical model imposes a constraint to the network output, making it effectively interpretable. We experimentally demonstrate the proposed GI technique by imaging a flying drone, and show that it outperforms some other widespread GI techniques in terms of both spatial resolution and sampling ratio. We believe that this study provides a new framework for GI, and paves a way for its practical applications.

Generation of in situ CRISPR-mediated primary and metastatic cancer from monkey liver.

Non-human primates (NHPs) represent the most valuable animals for drug discovery. However, the current main challenge remains that the NHP has not yet been used to develop an efficient translational medicine platform simulating human diseases, such as cancer. This study generated an in situ gene-editing approach to induce efficient loss-of-function mutations of Pten and p53 genes for rapid modeling primary and metastatic liver tumors using the CRISPR/Cas9 in the adult cynomolgus monkey. Under ultrasound guidance, the CRISPR/Cas9 was injected into the cynomolgus monkey liver through the intrahepatic portal vein. The results showed that the ultrasound-guided CRISPR/Cas9 resulted in indels of the Pten and p53 genes in seven out of eight monkeys. The best mutation efficiencies for Pten and p53 were up to 74.71% and 74.68%, respectively. Furthermore, the morbidity of primary and extensively metastatic (lung, spleen, lymph nodes) hepatoma in CRISPR-treated monkeys was 87.5%. The ultrasound-guided CRISPR system could have great potential to successfully pursue the desired target genes, thereby reducing possible side effects associated with hitting non-specific off-target genes, and significantly increasing more efficiency as well as higher specificity of in situ gene editing in vivo, which holds promise as a powerful, yet feasible tool, to edit disease genes to build corresponding human disease models in adult NHPs and to greatly accelerate the discovery of new drugs and save economic costs.

Sub-Nyquist ghost imaging by optimizing point spread function.

Point spread function (PSF) of ghost imaging (GI) with pseudo-thermal light source doesn't satisfy the property of space translation invariance and existing GI linear reconstruction algorithms offer images with low quality when the measurement process doesn't reach ergodic. By modifying the intensity value of the speckle patterns recorded by the camera in the reference path, the property of PSF can be optimized and a linear reconstruction method called optimized ghost imaging (OGI) is proposed to stably recover the object's image even in the measurements below Nyquist limit. In comparison with existing GI linear reconstruction algorithms, both the simulated and experimental results demonstrate that the image's SNR can be significantly enhanced by OGI especially when the sampling ratio is larger than 0.68 and the detection SNR is greater than 20 dB.

Ghost imaging of blurred object based on deep-learning.

In this paper, a new, to the best of our knowledge, neural network combining a new residual neural network (ResNetV2), the residual dense block (RDB), and eHoloNet is proposed to reconstruct a blurred object. With the theory of ghost imaging, only the bucket signal that passes through the blurred object is necessary for reconstruction. The training sets are ENMNIST, which is used for simulation, and the blurred object is designed by Airy convolution. To test the generalization of the neural network, we use multi-slit as the testing sets. Both simulated and experimental results show that the trained neural network is superior in a generalized reconstruction of the blurred object. In addition, the limitation of the reconstruction is also explained in this work.

Experimental investigation of chirped amplitude modulation heterodyne ghost imaging.

We have constructed a chirped amplitude modulation heterodyne ghost imaging (CAM-HGI) experimental system that demonstrates a robust ability against background light in experiments. In the experiments, the background light is simulated by irradiating a spatiotemporal random modulated light field onto the target. The effects of background light, modulation depth and modulation duration of the signal light source on CAM-HGI are investigated experimentally. The results show that the quality of CAM-HGI can be improved by increasing the modulation depth and the modulation duration of the signal light source, and more importantly, an image with a good signal-to-noise ratio (SNR) can be achieved even when the irradiation SNR is lower than -30 dB. This technique of CAM-HGI has an important application prospect for laser imaging in strong background light environments.

Focal-plane three-dimensional imaging method based on temporal ghost imaging: a proof of concept simulation.

A new focal-plane three-dimensional (3D) imaging method based on temporal ghost imaging is proposed and demonstrated. By exploiting the advantages of temporal ghost imaging, this method enables the utilization of slow integrating cameras and facilitates 3D surface imaging within the framework of sequential flood-illumination and focal-plane detection. The depth information is achieved by a temporal correlation between received and reference signals with multiple-shot, and the reflectivity information is achieved by flash imaging with a single-shot. The feasibility and performance of this focal-plane 3D imaging method have been verified through theoretical analysis and numerical experiments.

Block matching low-rank for ghost imaging.

High-quality ghost imaging (GI) under low sampling is very important for scientific research and practical application. How to reconstruct high-quality image from low sampling has always been the focus of ghost imaging research. In this work, based on the hypothesis that the matrix stacked by the vectors of image's nonlocal similar patches is of low rank and has sparse singular values, we both theoretically and experimentally demonstrate a method that applies the projected Landweber regularization and blocking matching low-rank denoising to obtain the excellent image under low sampling, which we call blocking matching low-rank ghost imaging (BLRGI). Comparing with these methods of "GI via sparsity constraint," "joint iteration GI" and "total variation based GI," both simulation and experiment show that the BLRGI can obtain better ghost imaging quality with low sampling in terms of peak signal-to-noise ratio, structural similarity index and visual observation.

A Dual Targeting Magnetic Nanoparticle for Human Cancer Detection.

Malignant tumors are a major threat to human life and high lymphatic vessel density is often associated with metastatic tumors. With the discovery of molecules targeted at the lymphatic system such as lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) and Podoplanin, many studies have been performed to determine the role of lymphatic endothelial cells (LECs) in tumor metastasis. However, disadvantages such as non-specificity and high cost limit their research and diagnostic applications. In this study, Fe3O4@KCTS, a core-shell type of magnetic nanoparticles, was prepared by activating Fe3O4 with carbodiimide and cross-linking it with α-ketoglutarate chitosan (KCTS). The LYVE-1 and Podoplanin antibodies were then incorporated onto the surface of these magnetic nanoparticles and as a result, dual-targeting magnetic nanoprobes were developed. The experimental tests of this study demonstrated that a dual-targeting magnetic nanoprobe with high-purity LECs from tumor tissues was successfully developed, providing a basis for clinical application of LECs in colorectal cancer treatment as well as in early clinical diagnosis using bimodal imaging.

Generation of Cancer-Specific Cytotoxic PD-1- T Cells Using Liposome-Encapsulated CRISPR/Cas System with Dendritic/Tumor Fusion Cells.

T-cell immunotherapy is showing great promise and therefore undergoing intensive developments for cancer treatment. In this study, we applied liposome-encapsulated Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated protein-9 nuclease (Cas9) (CRISPR/Cas9) genome editing tool to specifically knock out the programmed death-1 (PD-1) gene from T cells (PD-1- T cells). We then activated these cells by dendritic/tumor fusion cells (FCs) and examined their anti-cancer potential. Results showed that, following the antigen presentation and activation by DC/HepG2 FCs, PD-1- T cells showed a significantly higher ability than PD-1+ T cells to proliferate, secrete pro-inflammatory cytokine IFN-γ, and kill HepG2 cells in vitro. Consistently, in vitro activated PD-1- T cells inhibited proliferation and induced apoptosis in HepG2 xenografts in vivo, leading to significantly suppressed tumor growth and improved mouse survival. Liposome-encapsulated CRISPR/Cas9 genome editing technology effectively knocked out PD-1 gene in T cells, stimulating T cell activation in response to DC/tumor FCs and affording T cell-mediated cancer immunotherapy. Our study provides evidence to target checkpoint receptors in adoptively transfected T cells, as a novel therapeutic modality for adoptive T cell transfer.

Ghost imaging LiDAR via sparsity constraints using push-broom scanning.

Ghost imaging LiDAR via sparsity constraints using push-broom scanning is proposed. It can image the stationary target scene continuously along the scanning direction by taking advantage of the relative movement between the platform and the target scene. Compared to conventional ghost imaging LiDAR that requires multiple speckle patterns staring the target, ghost imaging LiDAR via sparsity constraints using push-broom scanning not only simplifies the imaging system, but also reduces the sampling number. Numerical simulations and experiments have demonstrated its efficiency.

A novel label-free terbium(iii)-aptamer based aptasensor for ultrasensitive and highly specific detection of acute lymphoma leukemia cells.

Acute leukemia is a malignant clonal disease of hematopoietic stem cells with a high prevalence and mortality rate. However, there are no efficient tools to facilitate early diagnosis and treatment of leukemia. Therefore, development of new methods for the early diagnosis and prevention of leukemia, especially non-invasive diagnosis at the cellular level, is imperative. Here, a label-free signal-on fluorescence aptasensor based on terbium(iii)-aptamer (Tb3+-apt) was applied for the detection of leukemia. The aptamer sensitizes the fluorescence of Tb3+ and forms the strong fluorescent Tb3+-apt probe. The target cells, the T-cell acute lymphoblastic leukemia cell line (CCRF-CEM) combined with the Tb3+-apt probe to form the Tb3+-apt-CEM complex, were removed by centrifugation, and the supernatant containing a small amount of the Tb3+-apt probe was detected using a fluorescence spectrophotometer. The logarithm of cell concentration showed a good linear relationship (R2 = 0.9881) with the fluorescence signal. The linear range for CCRF-CEM detection was 5-5 × 106 cells per ml, while the detection limit was 5 cells per ml of the binding buffer. Clinical samples were collected from 100 cases, and the specificity and positive rates detected by this method were up to 94% and 90%, respectively. Therefore, a single-stranded DNA-sensitized terbium(iii) luminescence method diagnostic was developed which is rapid, sensitive, and economical and can be used for diagnosis of various types of leukemia at the early stage.

Magnetic Endoglin Aptamer Nanoprobe for Targeted Diagnosis of Solid Tumor.

Based on molecular targeting, magnetic resonance imaging (MRI) is an ideal noninvasive approach for tumor diagnosis. Construction of targeting probes to enhance the MRI efficacy has become a research hotspot recently. In this study, magnetic endoglin aptamer (mEND) imaging nanoprobes based on mEND-modified magnetic carboxymethyl chitosan (CMCS) nanoparticles (denoted mEND-Fe3O4@CMCS) were developed. The mEND-Fe3O4@CMCS naoprobe was prepared using mEND as the recognition molecule and Fe3O4@CMCS as the carrier to enhance the MRI efficacy of hepatocellular carcinoma (HCC). On the one hand, the CMCS self-assembled on the surface of Fe3O4 improved the biocompatibility and nontoxicity of magnetic nanoparticles. On the other hand, chemical groups provided by CMCS contributed to the modification of more aptamers. More importantly, the assembled aptamers significantly improved the probe targeting ability, thus enhancing the diagnosis efficacy of MRI of HCC. As a result, the average diameter and zeta potential of the nanoprobe was 87.15±1.66 nm and -31.9±0.5 mV, respectively. The MRI imaging result indicated that this probe effectively targeted neovascularization of mouse HCC and improved the imaging contrast of subcutaneous tumor in mice. Cytotoxicity and histological tests confirmed that the constructed probe possessed low toxicity. In conclusion, the mEND-Fe3O4@CMCS nanoprobe showed high targeting affinity, enhanced MRI effect and good biocompatibility. This study provides new MRI probes to target CD105 positive cells and is a promising candidate for HCC early diagnosis.

TLS11a Aptamer/CD3 Antibody Anti-Tumor System for Liver Cancer.

New therapeutic approaches are needed for hepatocellular carcinoma (HCC), which is the most common primary malignancy of the liver. Bispecific T-cell engagers (BiTE) can effectively redirect T cells against tumors and show a strong anti-tumor effect. However, the potential immunogenicity, complexity, and high cost significantly limit their clinical application. In this paper, we used the hepatoma cells-specific aptamer TLS11a and anti-CD3 for to establish an aptamer/antibody bispecific system (AAbs), TLS11a/CD3, which showed advantages over BiTE and can specifically redirect T cells to lyse tumor cells. TLS11a-SH and anti-CD3-NH2 were crosslinked with sulfosuccinimidyl 4-(N-maleimidomethyl) cyclohexane-1-carboxylate (sulfo-SMCC). T cell activation, proliferation, and cytotoxicity of TLS11a/CD3 were analyzed by flow cytometry. Cytokine array was used to detect cytokine released from activated T cells. Hepatoma xenograft model was used to monitor the tumor volume and survival. TLS11a/CD3 could specifically bind hepatoma cells (H22) and T cells, activated T cells to mediate antigen-specific lysis of H22 cells in vitro, and effectively inhibited the growth of implanted H22 tumors as well as prolonged mice survival. TLS11a/CD3 could simultaneously target hepatoma cells and T cells, specifically guide T cells to kill tumor cells, and enhance the anti-tumor effect of T cells both in vitro and in vivo.

Generation of a Graft versus Anticancer Immune Response Through Skin Allograft with Tumor.

Effector memory T cells (TEM) are a subset of memory T cells which play an important role in stimulation of adaptive immunity. Although they are associated with multiple immune responses, the antitumor effect of TEM is not clearly understood. In this research, generation of anti-tumor TEM was induced through skin allografts in C57BL/6 mice with B16 melanoma. We observed that the growth of tumor tissues in C57BL/6 mice treated with allografts was interrupted. Furthermore, the survival time for the treated mice was prolonged along with increased serum levels for CXCL9, CXCL10 and INF-γ. Additionally, the concentrations of TEM in the spleens, lymph nodes and tumor tissues were markedly elevated in allografts treated mice. The tumor cell proliferation and tissue growth were suppressed in C57BL/6 mice with B16 melanoma induced by allografts, upon tail vein injection of purified TEM. These results demonstrate that skin allografts promote the generation of anti-tumor TEM in C57BL/6 mice with B16 melanoma, which emphasize the strong promise of TEM stimulation using allografts transplants in effective tumor immunotherapy.

Graphene-Based Multifunctional Nanomaterials in Cancer Detection and Therapeutics.

Nanotechnology for early diagnosis and treatment of malignant tumor is a forefront topic in the international field of biotechnology and medicine. In order to improve the effect of cancer therapy, the timely and accurate detection of the cancer is important and necessary. Graphene and its derivatives have various excellent characteristics. For example, biological sensors based on graphene are good at amplifying detection signals, and its derivatives play an important role in the early diagnosis and cancer therapy. In view of this, we discussed the biological sensor application based on graphene and its derivatives in the detection and therapy of cancer.

Recent Progress of Wnt Pathway Inhibitor Dickkopf-1 in Liver Cancer.

Hepatocellular carcinoma (HCC) is one of the most common cancers around the world. Multiple etiologic factors such as virus and environment can lead to HCC. It is a challenge for us to successfully detect early HCC due to the lack of effective characterized and specific biomarkers. However, if the early diagnosis is successfully realized, it provides crucial chance for HCC patients to receive effective treatment as early as possible. Dickkopf-1 (DKK-1) is a secretary glycoprotein, which negatively regulates Wnt pathway through binding to surface receptors LRP5/6 and Kremen 1/2. The expression of DKK-1 is regulated by p53, V-Myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN), ß-catenin, etc. Ectopic expression of DKK-1 can inhibit cell proliferation, or induce apoptosis with apoptosis enhancing factors. DKK-1 is low-expressed in many tumors, but overexpressed in others. Growing evidences show that DKK-1 plays complex and different roles in tumorigenesis, tumor progression and metastasis of different cancers. We herein review the recent progress in the expression and function of DKK-1 in hepatocellular carcinoma.

Ghost imaging via sparse structured illumination source.

We generate a type of pseudo-thermal light field via sparse structured illumination source. Genetic algorithm is utilized to optimize the source's spatial configuration and the property of pseudo-thermal light field is improved. Both simulated and experimental results demonstrate that the periodic distribution of normalized second-order intensity correlation function is effectively suppressed by optimizing the spatial configuration of sparse structured illumination source and the quality of ghost imaging can be obviously increased. This optimized sparse structured illumination source may be applied to the applications like remote sensing with moving targets.