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Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved. OBJECTIVES: The study compared the performance for detection and grading of coronary stenoses using artificial intelligence-enabled quantitative coronary computed tomography angiography (AI-QCT) analyses to core lab-interpreted coronary computed tomography angiography (CTA), core lab quantitative coronary angiography (QCA), and invasive fractional flow reserve (FFR). BACKGROUND: Clinical reads of coronary CTA, especially by less experienced readers, may result in overestimation of coronary artery disease stenosis severity compared with expert interpretation. AI-based solutions applied to coronary CTA may overcome these limitations. METHODS: Coronary CTA, FFR, and QCA data from 303 stable patients (64 ± 10 years of age, 71% male) from the CREDENCE (Computed TomogRaphic Evaluation of Atherosclerotic DEtermiNants of Myocardial IsChEmia) trial were retrospectively analyzed using an Food and Drug Administration-cleared cloud-based software that performs AI-enabled coronary segmentation, lumen and vessel wall determination, plaque quantification and characterization, and stenosis determination. RESULTS: Disease prevalence was high, with 32.0%, 35.0%, 21.0%, and 13.0% demonstrating ≥50% stenosis in 0, 1, 2, and 3 coronary vessel territories, respectively. Average AI-QCT analysis time was 10.3 ± 2.7 minutes. AI-QCT evaluation demonstrated per-patient sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 94%, 68%, 81%, 90%, and 84%, respectively, for ≥50% stenosis, and of 94%, 82%, 69%, 97%, and 86%, respectively, for detection of ≥70% stenosis. There was high correlation between stenosis detected on AI-QCT evaluation vs QCA on a per-vessel and per-patient basis (intraclass correlation coefficient = 0.73 and 0.73, respectively; P < 0.001 for both). False positive AI-QCT findings were noted in in 62 of 848 (7.3%) vessels (stenosis of ≥70% by AI-QCT and QCA of

Nanocarrier-aided drug delivery techniques have improved the absorption and permeability of drugs in nose-to-brain delivery. However, the molecular properties of nanocarriers during the delivery process are of great interest; in particular, the characteristics when penetrating barriers in vivo are crucial for the screening and optimization of materials for nasal inhalation. In this study, we have focused on two types of delivery systems: mucoadhesive nanoparticles (MAPs) and mucopenetrating nanoparticles (MPPs); both have been widely used for mucosal delivery, although a method for selecting the more effective type of drug carriers for mucosal delivery has not been established. Molecular dynamics (MD) simulations were used to reveal the all-atom dynamic characteristics of the interaction between different delivery systems and the nasal mucus protein MUC5AC. Among the systems tested, hydroxypropyltrimethyl ammonium chloride chitosan (HTCC) had the strongest interaction with mucin, suggesting it had better mucoadhesive performance, and that it interacted with MUC5AC more strongly than unmodified chitosan. In contrast, the mucus-penetrating material polyethylene glycol-poly lactic acid-co-glycolic acid (PEG-PLGA), had almost no interaction with MUC5AC. The results of the MD simulations were verified by in vitro experiments on nanoparticles (NPs) and mucin binding. The drug delivery performance of the four types of NPs, analyzed by in vitro and ex vivo mucosal penetration, were all generally consistent with the properties of the material predicted from the MD simulation. These clues to the molecular mechanism of MAPs and MPPs may provide useful insight into the screening and optimization of nanomaterials suitable for nasal inhalation.

Recently, hydrogel dressings have been rapidly developed for wound healing. However, it is still a huge challenge to endow hydrogel wound dressings with excellent hemostatic performance. Here, a new wound treatment material, foam gel wound dressing, is reported, which possesses rapid hemostasis and antibacterial properties. The foam gel dressing is composed of chitooligosaccharide modified graphene oxide (CG) nanocomposites and calcium alginate foam substrate. In this system, CG has a strong interaction with platelets, which is helpful for rapid hemostasis. So the wound dressing could stop bleeding quickly within 10 s. Meanwhile, CG also provides excellent antibacterial properties to dressings, which is conducive to wound healing. Full-thickness wound healing experiments showed that compared with blank control and CG-free foam gel dressings, CG-loaded foam gel dressings shows better healing properties, and the wounds covered with them are almost completely healed within 12 days. In addition, histological morphology analysis displays CG-loaded wound dressing could significantly accelerate wound healing by reducing the inflammatory response and promoting vascular remodeling. This unique strategy provides a simple and practical method for the clinical application of the next generation of wound dressings.

Half of all of China's lakes are on the Qinghai-Tibet Plateau (QTP), which are mainly distributed at altitudes above 4000 m asl. Being under conditions of progressively intensifying anthropogenic activities and climate change, the debate on whether QTP lakes act as carbon (C) sinks or sources remains unresolved. This study explores QTP lake C exchange processes and characteristics over the past two decades through field monitoring and data integration. Results reveal high lake carbon dioxide (CO

In monkey neuroimaging, particularly magnetic resonance imaging (MRI) studies, quick and accurate automatic macaque brain segmentation is essential. However, there are few processing and analysis tools dedicated to automatic brain tissue segmentation and labeling of the macaque brain on a subject-specific basis. As a result, currently most adopted methods are through direct implementation of existing tools that have been designed for human brain. However, the operation steps combining different functional modules of a variety of processing and analysis tool software are inevitably complicated, cumbersome, time-consuming and labor-intensive.In this study, we proposed a novel quick and accurate automatic macaque brain segmentation method based on multi-atlas registration and majority-vote algorithm. First, the single-atlas method based on S-HAMMER is used to register each template image of the reference atlas set (including brain tissue labeled images and brain anatomical structure labeled images) to the preprocessed image to be segmented. Thus, we obtain the corresponding deformation field and spatially transform the labeled image, and then get multiple segmentation results by local weighted voting method, which perform label fusion to obtain the final labeled images of brain structures segmentation result.By collecting high SNR and high spatial resolution images of macaque brain images from our 7T human MRI scanner, we have constructed two brain templates for each individual macaque subject, and macaque brain tissues and brain anatomical structure by one-atlas method. However, segmentation result of single-atlas method is not much accurate in some brain tissue area. It takes about 2 h and need more manual correction for segmentation. Automatic segmentation of macaque brain structure based on multi-atlas method was reasonably successful, the accuracy of segmentation was greatly improved without manual correction. Also, the proposed method provided good tissue fitting to V1 with smooth and continuous boundary. The Dice similarity of multi-atlas method showing 3.24%, 4.24%, 2.55%, 2.85%, 3.05%, and 0.35% improvement in image slices of 63, 66, 70, 71, 99 and 100, respectively. The entire processing time for the construction of a single template map took ~40 min.This study proposed a novel automatic segmentation method of individual macaque brain structure based on multi-atlas registration method, which is concise and reliable. It may offer a valuable tool to applications in the field of brain and neuroscience research using the macaque as an experimental animal model.

Creep age forming (CAF) is an advanced forming technology that combines creep deformation and age hardening processes. When compared with the conventional forming technologies including roll bending and shot-peen forming, CAF has many advantages of low residual stress, excellent dimensional stability, good service performance and short production cycle. It is an optimal technique for precise manufacturing for shape and properties of large-scale complicated thin-walled components of light-weight and high strength aluminum alloys in the aviation and aerospace industries. Nevertheless, CAF has an inevitable disadvantage that a large amount of springback occurs after unloading, which brings a challenge on the accurate shape forming and property tailoring of components. Therefore, how to achieve accurate prediction and control of springback has always been a bottleneck hindering the development of CAF to more industrial applications. After the factors of affecting springback and measures of reducing springback are summarized from the internal and external aspects, constitutive models for predicting springback and springback compensation methods for CAF of aluminum alloy panel components are reviewed. Then, a review of research progresses on tool design for CAF is presented. Finally, in view of the key issue that it is difficult to predict and control the shape and properties of components during CAF, the technical challenges are discussed and future development trends of CAF are prospected.

The treatment for epidermal bacterial infections has become a primary healthy concern, producing a significant therapeutic challenge. Here we present a facile strategy to fabricate lecithin/chitosan nanoparticles (LCNPs) for efficient epidermal drug delivery over epidermal bacterial infections. The central rotatable composite design method was used for the optimization of the preparation, and that the optimal size (212.63 ± 1.95 nm) was obtained via analysis of variance (ANOVA). The prepared CIP-LCNPs show an average diameter of 325.9 ± 7.4 nm and a zeta potential of 26.6 ± 1.2 mV. Antibiotics can be well encapsulated in LCNPs and its release kinetics is studied with cumulative release of 93.81 ± 2.05 % for 48 h. The hemolytic activity, cytotoxicity, and skin irritation are further investigated. The zones of inhibition are 2.16 ± 0.04 cm and 2.92 ± 0.03 cm for Escherichia coli and Staphylococcus aureus, respectively. Moreover, in vitro permeation studies demonstrate that LCNPs can increase the accumulation of antibiotics in the epidermis with retention ratio 2-3 fold higher than commercial formulations. The in vivo result over epidermal-infected wound demonstrates the superior therapeutic effects of LCNPs. The developed LCNPs represent an important advance in fabricating therapeutic materials for enhanced therapy over epidermal bacterial infections.

Adaptive postural control is an important yet underexamined area in children with developmental coordination disorder (DCD). This study compared adaptive postural responses between children with DCD and those with typical development.This was an exploratory cross-sectional study. Fifty-two children with DCD (aged 6-9 years) and 52 age- and sex-matched children with typical development participated in the study. Their adaptive postural (motor) responses were assessed using the Adaptation Test (ADT) on a computerized dynamic posturography machine. The sway energy score (SES) for each ADT trial and the average SES of five trials for both toes-up and toes-down platform inclination conditions were recorded.The SESs were lower in the DCD group than in the control group in ADT toes-up trial 1 (p = 0.009) and on average (p = 0.044). In the control group, the SES decreased from trial 1 to trial 2 for both the ADT toes-up (p = 0.005) and toes-down conditions (p 0.001).Adaptive postural responses were absent in children with DCD, and these children used less force (i.e., sway energy) to overcome postural instability. Therefore, both adaptive balance and neuromuscular training should be factored into rehabilitation programs for children with DCD.

Sialic acid-bound immunoglobulin lectin 15 (Siglec-15) plays a crucial role in many kinds of tumors. The relationship between Siglec-15 and the prognosis of osteosarcoma patients and its role in the apoptosis and pyroptosis of osteosarcoma cells are not sufficiently understood. Our study aimed to investigate the function of Siglec-15 in osteosarcoma cells and its effect on tumor cell proliferation, apoptosis and pyroptosis.The Siglec-15 expression in pathological sections of osteosarcoma patients was analyzed and the overall survival time related to the expression of Siglec-15 was further analyzed. Next, we detected the expression of Siglec-15 in osteosarcoma cells and downregulated the expression of Siglec-15 by small interfering RNA (siRNA). The proliferation, apoptosis and pyroptosis of osteosarcoma cells were studied by proliferation and apoptosis kits and Western blotting. Furthermore, the Siglec-15 signaling pathway was examined, which may be involved in the observed cellular effects.We demonstrated the expression of Siglec-15 in osteosarcoma cells. SiRNA-mediated downregulation of Siglec-15 was successful. We found that knockdown of Siglec-15 in osteosarcoma cell lines significantly inhibited proliferation while promoting apoptosis. Further investigation showed that the expression of proliferation-related proteins was downregulated and that apoptosis- and pyroptosis-related proteins were upregulated. In addition, we found that Siglec-15 may inhibit proliferation while inducing apoptosis and pyroptosis via the (Signal Transducer and Activator of Transcription 3) STAT3/Bcl-2 pathway in osteosarcoma.In this study, we demonstrated that the ablation of Siglec-15 in osteosarcoma inhibited proliferation and promoted apoptosis and pyroptosis by targeting the Siglec-15/STAT3/Bcl-2 pathway.

Infectious hypodermal and haematopoietic necrosis virus (IHHNV) is the smallest known virus in shrimp, which causes runt-deformity syndrome (RDS) and leads to huge economic loss every year in penaeid shrimp farming. Previous studies have shown that the juvenile Penaeus vannamei is more susceptible to IHHNV infection than the adults, but the mechanism is still unclear. In order to investigate the mechanism of pathogenic differences in IHHNV infection of P. vannamei at different developmental stages, the juvenile and adult P. vannamei were studied by transcriptome high-throughput sequencing to analyze their response to IHHNV infection. GO and KEGG enrichment were analyzed to search for differentially expressed genes (DEGs) related to immunity, growth and metabolism. The results showed that many immune-related genes of the juvenile and adult P. vannamei responded differently to IHHNV infection. For the adult P. vannamei, the expression of most immune-related genes was significantly up-regulated, which means that a cellular defense response was triggered after IHHNV infection. However, most immune-related genes in juvenile P. vannamei were inhibited, indicating that the immune system of juvenile the P. vannamei is imperfect and makes it to be more susceptible to IHHNV. Similarly, the growth-related genes of P. vannamei were changed during IHHNV infection. For the juvenile P. vannamei, the growth-related genes were significantly down-regulated, which resulted in a growth hormone disorder and prevented the juvenile P. vannamei from growth. In the adult P. vannamei, most molting-related genes were significantly up-regulated, indicating that IHHNV infection leads the adult P. vannamei to early molting to eliminate pathogen in the body. Metabolic process data showed that energy metabolism pathway was affected when P. vannamei infected with IHHNV. The adult P. vannamei infected with IHHNV can cause energetically costly and lead to the disturbance of the metabolism, activate complex immune systems to resist the invasion of pathogens. The results of this study clarified the response mechanism of P. vannamei at different developmental stages to IHHNV infection, which can provide new insights to IHHNV effective control and a reference for the study of sensitive period of different shrimp virus to host infection.

Diabetic vascular endothelial impairment is one of the main causes of death in patients with diabetes lacking adequately defined mechanisms or effective treatments. REGγ, the 11S proteasome activator known to promote the degradation of cellular proteins in a ubiquitin- and ATP-independent manner, emerges as a new regulator in the cardiovascular system. Here, we found that REGγ was upregulated in streptozocin (STZ)-induced diabetic mouse aortic endothelium in vivo and high glucose (HG)-treated vascular endothelial cells (ECs) in vitro. REGγ deficiency ameliorated endothelial impairment in STZ-induced diabetic mice by protecting against a decline in cellular glucose uptake and associated vascular ECs dysfunction by suppressing high mobility group AT-hook 2 (HMGA2) decay. Mechanically, REGγ interacted with and degraded the transcription factor HMGA2 directly, leading to decreased HMGA2 transcriptional activity, subsequently lowered expression of glucose transporter type 1 (GLUT1), and reduced cellular glucose uptake, vascular endothelial dysfunction, and impaired diabetic endothelium. Ablation of endogenous GLUT1 or HMGA2 or overexpressing exogenous HMGA2 in vascular ECs significantly blocked or reestablished the REGγ-dependent action on cellular glucose uptake and vascular endothelial functions of HG stimulation in vitro. Furthermore, exogenously introducing HMGA2 improved diabetic mice endothelial impairment features caused by REGγ in vivo, thereby substantiating a REGγ-HMGA2-GLUT1 pathway in diabetic endothelial impairment. Our findings indicate that modulating REGγ-proteasome activity may be a potential therapeutic approach for diabetic disorders with endothelial impairment.