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Pleiotrophin (PTN) is a growth factor with both pro-angiogenic and limited pro-tumorigenic activity. We evaluated the potential for PTN to be used for safe angiogenic gene therapy using the full length gene and a truncated gene variant lacking the domain i

This paper reviews published research in the field of computer-aided colorization technology. We argue that within this context, the colorization task can be considered to originate from computer graphics, advance by introducing computer vision, and progress towards the fusion of vision and graphics. Hence, we propose a specific taxonomy and organize the research work chronologically. We extend the existing reconstruction-based colorization evaluation techniques on the basis that aesthetic assessment should be introduced to ensure the computer- colored images closely satisfy human visual-related requirements. We then perform an aesthetic assessment using the proposed metric and existing evaluations, comparing the colorization performance of seven representative unconditional colorization models. Finally, we identify unresolved issues and propose fruitful areas for future research and development. Details of the project associated with this survey can be obtained at https://github.com/DanielCho-HK/Colorization.

Being essential in animation creation, colorizing anime line drawings is usually a tedious and time-consuming manual task. Reference-based line drawing colorization provides an intuitive way to automatically colorize target line drawings using reference images. The prevailing approaches are based on generative adversarial networks (GANs), yet these methods still cannot generate high-quality results comparable to manually-colored ones. In this article, a new AnimeDiffusion approach is proposed via hybrid diffusions for the automatic colorization of anime face line drawings. This is the first attempt to utilize the diffusion model for reference-based colorization, which demands a high level of control over the image synthesis process. To do so, a hybrid end-to-end training strategy is designed, including phase 1 for training diffusion model with classifier-free guidance and phase 2 for efficiently updating color tone with a target reference colored image. The model learns denoising and structure-capturing ability in phase 1, and in phase 2, the model learns more accurate color information. Utilizing our hybrid training strategy, the network convergence speed is accelerated, and the colorization performance is improved. Our AnimeDiffusion generates colorization results with semantic correspondence and color consistency. In addition, the model has a certain generalization performance for line drawings of different line styles. To train and evaluate colorization methods, an anime face line drawing colorization benchmark dataset, containing 31,696 training data and 579 testing data, is introduced and shared. Extensive experiments and user studies have demonstrated that our proposed AnimeDiffusion outperforms state-of-the-art GAN-based methods and another diffusion-based model, both quantitatively and qualitatively.

Efforts in precision medicine to combat aberrant epigenome have led to the development of epigenetic targeting drugs. We have previously reported the capability of the BZD9L1 epigenetic modulator to impede colorectal tumour growth in vitro and in vivo through sirtuin (SIRT) inhibition. Although most benzimidazole derivatives are commonly less toxic, their effects on SIRTs and cytochrome P450 (CYP) regulations have not been explored alongside toxicity assessments. SIRTs are histone deacetylases that are crucial in maintaining metabolic homeostasis, whereas CYP is essential in drug metabolism. This study aims to determine the toxicology profile of BZD9L1 through oral acute and repeated dose toxicity evaluations, along with molecular analyses of SIRT, CYP and relevant toxicity markers through western blot and quantitative polymerase chain reaction (qPCR). BZD9L1 demonstrated no sign of acute toxicity at the limit dose (2000 mg/kg). The 28-day toxicity study highlighted the tolerability of repeated dose administration without adverse effects. BZD9L1 showed a sex-divergent regulation of hepatic SIRT1-7, CYP2A5 and CYP2D proteins. Furthermore, BZD9L1 did not induce the expression of organ injury proteins or alter the gene expression of cellular function indicators in mouse liver and kidneys, hence demonstrating, at least in part, the safety of BZD9L1 in short-term evaluations. The present study cautions for personalised strategies when employing benzimidazole-derived epigenetic therapeutics., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Danon disease is an X-linked disorder that leads to fatal cardiomyopathy caused by a deficiency in lysosome-associated membrane protein-2 (LAMP2). In female patients, a later onset and less severe clinical phenotype have been attributed to the random inactivation of the X chromosome carrying the mutant diseased allele. We generated a patient-specific induced pluripotent stem cell (iPSCs)-based model of Danon disease to evaluate the therapeutic potential of Xi-chromosome reactivation using a DNA methylation inhibitor., Methods: Using whole-exome sequencing, we identified a nonsense mutation (c.520C>T, exon 4) of the LAMP2 gene in a family with Danon disease. We generated iPSC lines from somatic cells derived from the affected mother and her 2 sons, and we then differentiated them into cardiomyocytes (iPSC-CMs) for modeling the histological and functional signatures, including autophagy failure of Danon disease., Results: Our iPSC-CM platform provides evidence that random inactivation of the wild-type and mutant LAMP2 alleles on the X chromosome is responsible for the unusual phenotype in female patients with Danon disease. In vitro, iPSC-CMs from these patients reproduced the histological features and autophagy failure of Danon disease. Administration of the DNA demethylating agent 5-aza-2'-deoxycytidine reactivated the silent LAMP2 allele in iPSCs and iPSC-CMs in female patients with Danon disease and ameliorated their autophagy failure, supporting the application of a patient-specific iPSC platform for disease modeling and drug screening., Conclusions: Our iPSC-CM platform provides novel mechanistic and therapeutic insights into the contribution of random X chromosome inactivation to disease phenotype in X-linked Danon disease., (© 2016 American Heart Association, Inc.)

Pleiotrophin (PTN) is a growth factor with both pro-angiogenic and limited pro-tumorigenic activity. We evaluated the potential for PTN to be used for safe angiogenic gene therapy using the full length gene and a truncated gene variant lacking the domain implicated in tumorigenesis. Mouse myoblasts were transduced to express full length or truncated PTN (PTN or T-PTN), along with a LacZ reporter gene, and injected into mouse limb muscle and myocardium. In cultured myoblasts, PTN was expressed and secreted via the Golgi apparatus, but T-PTN was not properly secreted. Nonetheless, no evidence of uncontrolled growth was observed in cells expressing either form of PTN. PTN gene delivery to myocardium, and non-ischemic skeletal muscle, did not result in a detectable change in vascularity or function. In ischemic hindlimb at 14 days post-implantation, intramuscular injection with PTN-expressing myoblasts led to a significant increase in skin perfusion and muscle arteriole density. We conclude that (1) delivery of the full length PTN gene to muscle can be accomplished without tumorigenesis, (2) the truncated PTN gene may be difficult to use in a gene therapy context due to inefficient secretion, (3) PTN gene delivery leads to functional benefit in the mouse acute ischemic hindlimb model.

It is generally accepted that there is a relationship between body dimensions, body movement and clothing wearing ease design, and yet previous research in this area has been neither sufficient nor systematic. This paper proposes a method to measure the human body in the static state and in 17 dynamic postures, so as to understand dimensional changes of different body parts during dynamic movements. Experimental work is carried out to collect 30 measurements of 10 male Chinese subjects in both static and dynamic states. Factor analysis is used to analyse body measurement data in a static state, and such key measurements describe the characteristics of different body figures. Moreover, one-way ANOVA is used to analyse how dynamic postures affect these key body measurements. Finally, an application of the research results is suggested: a dynamic block patternmaking method for high-performance clothing design., (Copyright © 2011 Elsevier Ltd and The Ergonomics Society. All rights reserved.)

Delivery of bone marrow cells (BMCs) to the heart has substantially improved cardiac function in most rodent models of myocardial infarction (MI), but clinical trials of BMC therapy have led to only modest improvements. Rodent models typically involve intramyocardial injection of BMCs from distinct donor individuals who are healthy. In contrast, autologous BMCs from individuals after MI are used for clinical trials. Using BMCs from donor mice after MI, we discovered that recent MI impaired BMC therapeutic efficacy. MI led to myocardial inflammation and an increased inflammatory state in the bone marrow, changing the BMC composition and reducing their efficacy. Injection of a general anti-inflammatory drug or a specific interleukin-1 inhibitor to donor mice after MI prevented this impairment. Our findings offer an explanation of why human trials have not matched the success of rodent experiments and suggest potential strategies to improve the success of clinical autologous BMC therapy.

A better understanding of the molecular mechanism of ligand-receptor interaction of glucagon-like peptide 1 (GLP-1) receptors (GLP-1Rs) is useful for the design of potent GLP-1 analogs that could potentially be used as a treatment for diabetic patients. Changes in the ligand and receptor sequences during evolution provide invaluable clues to evaluate the functional motifs of the receptor that are responsible for ligand interaction. For these reasons, in the present study, we have isolated and functionally characterized a GLP-1R from goldfish. Its amino acid sequence shows 50.8% and 52.3% identity with the human glucagon (hGLU) and GLP-1Rs, respectively, and 84.1% with the zebrafish GLP-1R (the only other GLP-1R isolated from teleost fish). Peptides that are structurally different from goldfish (gf)GLP-1, such as gfGLU and hGLU and human GLP-1 (7-36)amide, are also capable of stimulating this receptor, albeit with lower potencies than gfGLP-1. gfGLP-1 stimulates the formation of cAMP through the recombinant gfGLP-1R with EC(50) = 0.18 nM, whereas EC(50) values for gfGLU, human GLP-1 (7-36)amide, and hGLU are 0.53 nM, 0.9 nM, and 1.2 nM, respectively. These results indicate that the gfGLP-1R is structurally more flexible than its mammalian counterpart and that its binding pocket can accommodate a wider spectrum of peptide ligands. Previous studies demonstrated that the charged residues in the extracellular domains of mammalian GLP-1R, particularly those found in the N-terminal domain and the first exoloop, are important for ligand binding. We investigated the roles of the conserved charged residues in the function of the gfGLP-1R. Eleven mutant receptors were constructed, and the effects of mutations were determined by functional assays. Our results demonstrated that three charged residues (D(113), R(197), and D(205)) present in the extracellular domains are critical for receptor function.