Background
It has never been possible to immediately evaluate heart rate variability (HRV) during exercise. We aimed to visualize the real‐time changes in the power spectrum of HRV during exercise ...and to investigate its relationship to the ventilatory threshold (VT).
Methods and Results
Thirty healthy subjects (29.1±5.7 years of age) and 35 consecutive patients (59.0±13.2 years of age) with myocardial infarctions underwent cardiopulmonary exercise tests with an RAMP protocol ergometer. The HRV was continuously assessed with power spectral analyses using the maximum entropy method and projected on a screen without delay. During exercise, a significant decrease in the high frequency (HF) was followed by a drastic shift in the power spectrum of the HRV with a periodic augmentation in the low frequency/HF (L/H) and steady low HF. When the HRV threshold (HRVT) was defined as conversion from a predominant high frequency (HF) to a predominant low frequency/HF (L/H), the VO2 at the HRVT (HRVT‐VO2) was substantially correlated with the VO2 at the lactate threshold and VT) in the healthy subjects (r=0.853 and 0.921, respectively). The mean difference between each threshold (0.65 mL/kg per minute for lactate threshold and HRVT, 0.53 mL/kg per minute for VT and HRVT) was nonsignificant (P>0.05). Furthermore, the HRVT‐VO2 was also correlated with the VT‐VO2 in these myocardial infarction patients (r=0.867), and the mean difference was −0.72 mL/kg per minute and was nonsignificant (P>0.05).
Conclusions
A HRV analysis with our method enabled real‐time visualization of the changes in the power spectrum during exercise. This can provide additional information for detecting the VT.
Cell membranes actively change their local compositions, serving essential biological processes such as cellular signaling and endocytosis. Although membrane dynamics is vital in the cellular ...functions, the complexity of natural membranes has made its fundamental understanding and systematic assessment difficult. Here, a powerful artificial membrane system is developed for real‐time visualization of the spatiotemporal dynamics of membrane remodeling. Through well‐defined air/oil/water interfaces on grid holes, tens of planar lipid bilayer membranes are easily created, and their reproducibility, controllability, and generality are highlighted. The freestanding membranes are large but also highly stable, facilitating direct long‐term monitoring of dynamic membrane reconstitution caused by external stimuli. As an example to demonstrate the superiority of this membrane system, the effect of cholesterol trafficking, which significantly affects biophysical properties of cell membranes, is investigated at different membrane compositions. Cholesterol transport into and out of the membranes at different rates causes anomalous lipid arrangements through cholesterol‐mediated phase transitions and decomposition, which have never been witnessed before. Furthermore, enzyme‐induced membrane dynamics is successfully shown in this platform; sphingomyelinases locally generate asymmetry between two membrane leaflets. This technique is broadly applicable for exploring the membrane heterogeneity under various membrane‐based reactions, providing valuable insight into the membrane dynamics.
Wide‐spread, planar, and freestanding lipid bilayer membranes are constructed for real‐time observation of membrane dynamics at various conditions. With the help of well‐defined air/oil/water interfaces, tens of uniform membranes are simultaneously prepared. Due to their ultra‐high stability, dynamic membrane reorganization is easily visualized in control of biologically meaningful parameters such as membrane asymmetry, cholesterol transport, and enzymatic reactions.
Controlling the physical properties of interfacial polymerization (IP) plays a crucial role in tailoring the structures and properties of thin-film composite (TFC) membranes. However, due to the ...instantaneity and complexity of the IP reaction, it is challenging to determine the mechanism of the process and establish the connection between the synthesis-structure-performance. For the first time, novel characterization techniques that researchers have employed to visualize the IP reaction in real-time and several classical theoretical models for computer simulations of the IP process are discussed to reveal the intrinsic mechanisms of the IP process from the microscopic perspective. Furthermore, this paper also illustrates the latest effective strategies of IP technology to regulate the permeability and selectivity of membranes from a macroscopic perspective. The above discussion is vital to illustrate the synthesis-structure-performance relationships of TFC membranes, and is conducive to breaking the trade-off effect between permeability and selectivity. Finally, we highlight the potential and challenges of using the IP technology to synthesize TFC membranes for targeted separation applications. This review addressed the urgent need for comprehensive research on the IP process and provides a strong foundation for the advancement and improvement of polyamide (PA) membranes.
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•The application of visualization technologies for observation the interfacial polymerization (IP) proceess are described.•Classical computer theoretical models for the IP process simulation are summarized.•Multidimensional regulation of the IP technology is outlined for properties of thin-film composite (TFC) membranes.•The challenges and prospects in tailoring high-performance TFC membranes with the IP technology is presented.
See Herms and Schön (doi:
10.1093/brain/awx100
) for a scientific commentary on this article.
Glaucoma is often diagnosed late when vision loss has already occurred. Cordeiro
et al
. report a new ...fluorescent marker for retinal imaging that can safely visualise real-time
in vivo
neuronal apoptosis in patients. Increased labelling is observed in patients with progressive neurodegenerative disease compared to healthy controls.
See Herms and Schön (doi:
10.1093/brain/awx100
) for a scientific commentary on this article.
Retinal cell apoptosis occurs in many ocular neurodegenerative conditions including glaucoma—the major cause of irreversible blindness worldwide. Using a new imaging technique that we have called DARC (detection of apoptosing retinal cells), which until now has only been demonstrated in animal models, we assessed if annexin 5 labelled with fluorescent dye DY-776 (ANX776) could be used safely in humans to identify retinal cell apoptosis. Eight patients with glaucomatous neurodegeneration and evidence of progressive disease, and eight healthy subjects were randomly assigned to intravenous ANX776 doses of 0.1, 0.2, 0.4 and 0.5 mg in an open-label, phase 1 clinical trial. In addition to assessing the safety, tolerability and pharmacokinetics of ANX776, the study aimed to explore whether DARC could successfully visualize individual retinal cell apoptosis
in vivo
in humans, with the DARC count defined as the total number of unique ANX776-labelled spots. DARC enabled retinal cell apoptosis to be identified in the human retina using ANX776. Single ANX776-labelled cells were visualized in a dose-dependent pattern (
P <
0.001) up to 6 h after injection. The DARC count was significantly higher (2.37-fold, 95% confidence interval: 1.4–4.03,
P =
0.003) in glaucoma patients compared to healthy controls, and was significantly (
P =
0.045) greater in patients who later showed increasing rates of disease progression, based on either optic disc, retinal nerve fibre layer or visual field parameters. Additionally, the DARC count significantly correlated with decreased central corneal thickness (Spearman’s R = −0.68,
P =
0.006) and increased cup-disc ratios (Spearman’s R = 0.47,
P =
0.038) in glaucoma patients and with increased age (Spearman’s R = 0.77,
P =
0.001) in healthy controls. Finally, ANX776 was found to be safe and well-tolerated with no serious adverse events, and a short half-life (10–36 min). This proof-of-concept study demonstrates that retinal cell apoptosis can be identified in the human retina with increased levels of activity in glaucomatous neurodegenerative disease. To our knowledge, this is the first time individual neuronal apoptosis has been visualized
in vivo
in humans and is the first demonstration of detection of individual apoptotic cells in a neurodegenerative disease. Furthermore, our results suggest the level of apoptosis (‘DARC count’) is predictive of disease activity, indicating the potential of DARC as a surrogate marker. Although further trials are clearly needed, this study validates experimental findings supporting the use of DARC as a method of detection and monitoring of patients with glaucomatous neurodegeneration, where retinal ganglion cell apoptosis is an established process and where there is a real need for tools to non-invasively assess treatment efficacy.
A water-soluble fluorescent probe was designed for the real-time visualization of GGT activity. GGT can specifically catalyze the cleavage of γ-glutamyl linkage to release amino group, thus providing ...light-up fluorescence.
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•An activatable fluorescent probe has been developed for real-time visualization of γ-glutamyl transpeptidase activity.•This desinged probe showed high sensitivity, good water solubility and biocompatibility.•We successfully employed the probe to monitor GGT activity in HepG2 cells.
γ-glutamyl transpeptidase (GGT) is a kind of cell-surface enzyme that is overexpressed in many cancer cells. It is of great significance to develop an ideal tool for the diagnosis of GGT-rich cancer cells. Here, we reported a simple-structured but effective imaging probe for the detection of GGT activity. In the presence of GGT, the γ-glutamyl linkage could be cleaved specifically to produce amino-substituted product, resulting in significant fluorescence enhancement at 578 nm. Moreover, we successfully employed the probe to monitor GGT activity in HepG2 cells. We envisaged that such a simple but effective imaging tool could improve the practical applications for bioimaging.
In this graphical abstract, we present recent advancements in fluorescent probes for the potential detection and monitoring of various liver diseases, emphasizing diverse disease types and their ...associated biomarkers.
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•This review addresses liver diseases such as IRI, HCC, viral hepatitis, fatty liver, and liver fibrosis, which are major global health concerns.•This review underscores that fluorescent probes offer non-invasive, real-time visualization and high sensitivity detection, overcoming conventional diagnostic methods and advancing liver disease diagnosis.•This review emphasizes the use of innovative fluorescent probe designs for the enhanced detection of new biomarkers in liver diseases.•This review explores the potential of fluorescent probes in aiding precise surgical resection of liver tumors, and offers insights into future perspectives for liver disease detection and monitoring.
Liver disease is a significant global health burden, affecting millions of people worldwide. According to the World Health Organization, it accounts for ∼ 2 million deaths annually, making it one of the leading causes of global mortality. Early detection and accurate diagnosis of liver diseases, including ischemia–reperfusion injury (IRI), hepatocellular carcinoma (HCC), viral hepatitis, fatty liver disease, and liver fibrosis, are crucial to ensure effective treatment. Fluorescent probes have shown great potential in overcoming the limitations of conventional diagnostic methods by enabling real-time visualization and analysis of cellular and molecular events with high sensitivity and specificity. Although significant progress has been made in fluorescent probes for liver diseases, there is no comprehensive review published on this topic. This article presents a comprehensive review, examining the latest advancements in the development and application of fluorescent probes for liver disease detection and monitoring. It highlights innovative design strategies and probe types that improve targeting capabilities, photostability, and biocompatibility. Furthermore, this review discusses recent progress in detecting liver-specific biomolecules and processes, such as reactive oxygen species, enzyme activity, microenvironment, metal ions, apoptosis, etc., across various liver diseases, with particular emphasis on IRI and HCC. The challenges and limitations of using fluorescent probes for liver disease detection are addressed, and insights into future perspectives for the field are provided. This review serves as a valuable resource for understanding the current state and potential of fluorescent probes in the diagnosis and monitoring of liver diseases, with the ultimate goal of benefiting patients suffering from these debilitating conditions.
In this study, we propose ShapeGraMM (Shape Grammar for massive models), an expandable grammar that procedurally generates geometries in real-time to create 3D scenes of massive models. Procedural ...modeling has attracted attention for its ability to quickly create 3D scenes using a compact representation, which stores generation rules rather than an explicit representation of the scene. Our work is an extension of the Computer Generated Architecture (CGA) shape grammar specification. We introduce rules that will take the visibility of the camera into account and decide whether or not it should continue to generate. ShapeGraMM explores the repetitions and patterns present in massive models, helping it render scenes, reduce its memory footprint, and procedurally process the scene efficiently. We propose an engine implementation that generates scenes on the fly using ShapeGraMM, followed by its evaluation using massive real-world models. We conducted a case study testing our solution with large-scale CAD models of the oil & gas industry in the web context, which is a more limited platform than the desktop. In contrast to random models commonly generated by procedural generation methodologies, the original models of our study were modeled in a non-random method. Our results show that the solution has high performance and maintains a compact representation of the models offline and in runtime. The procedural engine renders a massive scene containing over 11 million objects at interactive frame rates.
•A new architecture of a procedural engine is proposed.•Procedural generation can be an alternative for the transmission of massive models on the web.•Large-scale CAD models can be generated on the fly and rendered at interactive rates.•Shape grammar can be an alternative format to embed accelerating structures of models.
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During the last two decades, designers have been embracing building information modeling (BIM) to improve the quality of the documentation that is produced as well as constructability. While BIM has ...become an innate feature of the design process within the construction industry, there have been limited investigations that have examined how it can be integrated into real-time communication on-site. In addressing this gap, this paper proposes a conceptual framework that integrates BIM with augmented reality (AR) so as to enable the physical context of each construction activity or task to be visualized in real-time. To be effective, it is suggested that AR should be ubiquitous (including context awareness) and thus operate in conjunction with tracking and sensing technologies such as radio frequency identification (RFID), laser pointing, sensors and motion tracking.
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