Studying the Inflammatory Responses to Amyloid Beta Oligomers in Brain-Specific Pericyte and Endothelial Co-Culture From Human Stem Cells

Background: Recently, the in vitro blood–brain barrier (BBB) models derived from human pluripotent stem cells have been given extensive attention in therapeutics due to the implications they have with the health of the central nervous system. It is essential to create an accurate BBB model in vitro in order to better understand the properties of the BBB, and how it can respond to inflammatory stimulation and be passed by targeted or non-targeted cell therapeutics, more specifically extracellular vesicles.Methods: Brain-specific pericytes (iPCs) were differentiated from iPSK3 cells using dual SMAD signaling inhibitors and Wnt activation plus fibroblast growth factor 2 (FGF-2). The derived cells were characterized by immunostaining, flow cytometry, and RT-PCR. In parallel, blood vessels organoids were derived using Wnt activation, BMP4, FGF2, VEGF, and SB431542. The organoids were replated and treated with retinoic acid to enhance the blood–brain barrier (BBB) features in the differentiated brain endothelial cells (iECs). Co-culture was performed for iPCs and iECs in the transwell system and 3D microfluidics channels.Results: The derived iPCs expressed common markers PDGFRb and NG2, and brain-specific genes FOXF2, ABCC9, KCNJ8, and ZIC1. The derived iECs expressed common endothelial cell markers CD31, VE-cadherin, and BBB-associated genes BRCP, GLUT-1, PGP, ABCC1, OCLN, and SLC2A1. The co-culture of the two cell types responded to the stimulation of amyloid β42 oligomers by the upregulation of the expression of TNFa, IL6, NFKB, Casp3, SOD2, and TP53. The co-culture also showed the property of trans-endothelial electrical resistance. The proof of concept vascularization strategy was demonstrated in a 3D microfluidics-based device.Conclusion: The derived iPCs and iECs have brain-specific properties, and the co-culture of iPCs and iECs provides an in vitro BBB model that show inflammatory response. This study has significance in establishing micro-physiological systems for neurological disease modeling and drug screening

AF-OSD: An Anchor-Free Oriented Ship Detector Based on Multi-Scale Dense-Point Rotation Gaussian Heatmap

Due to the complexity of airborne remote sensing scenes, strong background and noise interference, positive and negative sample imbalance, and multiple ship scales, ship detection is a critical and challenging task in remote sensing. This work proposes an end-to-end anchor-free oriented ship detector (AF-OSD) framework based on a multi-scale dense-point rotation Gaussian heatmap (MDP-RGH) to tackle these aforementioned challenges. First, to solve the sample imbalance problem and suppress the interference of negative samples such as background and noise, the oriented ship is modeled via the proposed MDP-RGH according to its shape and direction to generate ship labels with more accurate information, while the imbalance between positive and negative samples is adaptively learned for the ships with different scales. Then, the AF-OSD based on MDP-RGH is further devised to detect the multi-scale oriented ship, which is the accurate identification and information extraction for multi-scale vessels. Finally, a multi-task object size adaptive loss function is designed to guide the training process, improving its detection quality and performance for multi-scale oriented ships. Simulation results show that extensive experiments on HRSC2016 and DOTA ship datasets reveal that the proposed method achieves significantly outperforms the compared state-of-the-art methods

Single-Image Dehazing Using Extreme Reflectance Channel Prior

Image dehazing algorithms based on dark channel prior principle have achieved good results for most scenes. However, the popular dark channel prior tends to underestimate transmissions of bright areas or objects, such as the skies, white areas and self-luminous bodies, which may cause color distortions during dehazing. A complementary prior called the extreme reflectance channel prior (ERC), which combines the dark channel prior with the bright channel prior, is proposed to estimate the transmission map. The extreme reflectance channel is the union of dark and bright channel’s pixels which satisfy the corresponding channel. Based on the scattering analysis results that the intensities of pixels in ERC are often close to 0 or 1 for the natural haze-free images or close to global atmospheric light if hazes occur in the air, the pixels in a hazy image can be recovered according to ERC to calculate the transmission map and then solve the haze imaging mode. Experiments show that ERC method outperforms state-of-the-art methods in PSNR, SSIM and visual perception effects

Inducible T-cell co-stimulators regulate the proliferation and invasion of human hepatocellular carcinoma HepG2 cells

Abstract Background This study determined the regulatory effects of inducible T-cell co-stimulators (ICOS) in human hepatocellular carcinoma HepG2 cells using a RNA interference (RNAi) technique. Methods A RNAi technique was used to knockdown the expression of ICOS. ICOS expression after knockdown was detected as mRNA and protein levels by RT-PCR and Western blot, respectively. A MTT colorimetric assay was used to detect cell proliferation, and the Transwell assay was used to detect cell invasion. Western blot was carried out to detect the level of Bcl-2, AKT, and PI3K protein expression in different groups. Results The proliferation of HepG2 cells were significantly decreased after ICOS siRNA transfection (EG group). Similarly, the results of the Transwell experiment showed that invasion of HepG2 cells in the EG group was clearly reduced compared to the negative control (NC) and blank control groups (CON). Western blot analysis showed that knockdown of ICOS expression reduced the levels of Bcl-2 and AKT, and also significantly up-regulated the level of PI3K phosphorylation (P < 0.01). Conclusion Down-regulating ICOS expression in HepG2 cells suppressed cell proliferation and invasion. The underlying mechanism may be related to the expression of the downstream factor, PI3K/AKT

PET imaging of apoptosis in tumor-bearing mice and rabbits after paclitaxel treatment with (18)F(-)Labeled recombinant human His10-annexin V.

Monitoring response to chemo- or radiotherapy is of great importance in clinical practice. Apoptosis imaging serves as a very useful tool for the early evaluation of tumor response. The goal of this study was PET imaging of apoptosis with (18)F-labeled recombinant human annexin V linked with 10 histidine tag ((18)F-rh-His10-annexin V) in nude mice bearing an A549 tumor and rabbits bearing a VX2 lung cancer after paclitaxel therapy. (18)F-rh-His10-annexin V was prepared by conjugation of rh-His10-annexin V with N-succinimidyl 4-[(18)F]fluorobenzoate. Biodistribution was determined in mice by the dissection method and small-animal PET. Single-dose paclitaxel (175 mg/m(2)) was used to induce apoptosis in A549 and VX2 tumor models. (18)F-rh-His10-annexin V was injected into A549 mice and VX rabbits to acquire dynamic and static PET images 72 h after paclitaxel treatment. The uptake of (18)F-rh-His10-annexin V in apoptotic cells 4 h after induction was 6.45±0.52 fold higher than that in non-induced cells. High focal uptake of (18)F-rh-His10-annexin V was visualized in A549 (SUVmax: 0.35±0.13) and VX2 (0.41±0.23) tumor models after paclitaxel treatment, whereas lower uptake was found in the corresponding tumors before treatment (A549 SUVmax: 0.04±0.02; VX2: 0.009±0.002). The apoptotic index was 75.61±11.56% in the treated VX2 cancer, much higher than that in the untreated VX2 (8.03±2.81%). This study demonstrated the feasibility of (18)F-rh-His10-annexin V for the detection of apoptosis after chemotherapy in A549 and VX2 tumor models

Plasma proteome profiling reveals dynamic of cholesterol marker after dual blocker therapy

Abstract Dual blocker therapy (DBT) has the enhanced antitumor benefits than the monotherapy. Yet, few effective biomarkers are developed to monitor the therapy response. Herein, we investigate the DBT longitudinal plasma proteome profiling including 113 longitudinal samples from 22 patients who received anti-PD1 and anti-CTLA4 DBT therapy. The results show the immune response and cholesterol metabolism are upregulated after the first DBT cycle. Notably, the cholesterol metabolism is activated in the disease non-progressive group (DNP) during the therapy. Correspondingly, the clinical indicator prealbumin (PA), free triiodothyronine (FT3) and triiodothyronine (T3) show significantly positive association with the cholesterol metabolism. Furthermore, by integrating proteome and radiology approach, we observe the high-density lipoprotein partial remodeling are activated in DNP group and identify a candidate biomarker APOC3 that can reflect DBT response. Above, we establish a machine learning model to predict the DBT response and the model performance is validated by an independent cohort with balanced accuracy is 0.96. Thus, the plasma proteome profiling strategy evaluates the alteration of cholesterol metabolism and identifies a panel of biomarkers in DBT