The γ-secretase substrate proteome and its role in cell signaling regulation.

γ-Secretases mediate the regulated intramembrane proteolysis (RIP) of more than 150 integral membrane proteins. We developed an unbiased γ-secretase substrate identification (G-SECSI) method to study to what extent these proteins are processed in parallel. We demonstrate here parallel processing of at least 85 membrane proteins in human microglia in steady-state cell culture conditions. Pharmacological inhibition of γ-secretase caused substantial changes of human microglial transcriptomes, including the expression of genes related to the disease-associated microglia (DAM) response described in Alzheimer disease (AD). While the overall effects of γ-secretase deficiency on transcriptomic cell states remained limited in control conditions, exposure of mouse microglia to AD-inducing amyloid plaques strongly blocked their capacity to mount this putatively protective DAM cell state. We conclude that γ-secretase serves as a critical signaling hub integrating the effects of multiple extracellular stimuli into the overall transcriptome of the cell.

Functionalized DNA Origami-Enabled Detection of Biomarkers.

Biomarkers are crucial physiological and pathological indicators in the host. Over the years, numerous detection methods have been developed for biomarkers, given their significant potential in various biological and biomedical applications. Among these, the detection system based on functionalized DNA origami has emerged as a promising approach due to its precise control over sensing modules, enabling sensitive, specific, and programmable biomarker detection. We summarize the advancements in biomarker detection using functionalized DNA origami, focusing on strategies for DNA origami functionalization, mechanisms of biomarker recognition, and applications in disease diagnosis and monitoring. These applications are organized into sections based on the type of biomarkers - nucleic acids, proteins, small molecules, and ions - and concludes with a discussion on the advantages and challenges associated with using functionalized DNA origami systems for biomarker detection.

Improving Molecular Dynamics Simulations for Solid-Liquid Interface with Machine Learning Interatomic Potentials.

Emerging developments in artificial intelligence have opened infinite possibilities for material simulation. Depending on the powerful fitting of machine learning algorithms to first-principles data, machine learning interatomic potentials (MLIPs) can effectively balance the accuracy and efficiency problems in molecular dynamics (MD) simulations, serving as powerful tools in various complex physicochemical systems. Consequently, this brings unprecedented enthusiasm for researchers to apply such novel technology in multiple fields to revisit the major scientific problems that have remained controversial owing to the limitations of previous computational methods. Herein, we introduce the evolution of MLIPs, provide valuable application examples for solid-liquid interfaces, and present current challenges. Driven by solving multitudinous difficulties in terms of the accuracy, efficiency, and versatility of MLIPs, this booming technique, combined with molecular simulation methods, will provide an underlying and valuable understanding of interdisciplinary scientific challenges, including materials, physics, and chemistry.

Climate control on terrestrial biospheric carbon turnover.

Terrestrial vegetation and soils hold three times more carbon than the atmosphere. Much debate concerns how anthropogenic activity will perturb these surface reservoirs, potentially exacerbating ongoing changes to the climate system. Uncertainties specifically persist in extrapolating point-source observations to ecosystem-scale budgets and fluxes, which require consideration of vertical and lateral processes on multiple temporal and spatial scales. To explore controls on organic carbon (OC) turnover at the river basin scale, we present radiocarbon (14C) ages on two groups of molecular tracers of plant-derived carbon-leaf-wax lipids and lignin phenols-from a globally distributed suite of rivers. We find significant negative relationships between the 14C age of these biomarkers and mean annual temperature and precipitation. Moreover, riverine biospheric-carbon ages scale proportionally with basin-wide soil carbon turnover times and soil 14C ages, implicating OC cycling within soils as a primary control on exported biomarker ages and revealing a broad distribution of soil OC reactivities. The ubiquitous occurrence of a long-lived soil OC pool suggests soil OC is globally vulnerable to perturbations by future temperature and precipitation increase. Scaling of riverine biospheric-carbon ages with soil OC turnover shows the former can constrain the sensitivity of carbon dynamics to environmental controls on broad spatial scales. Extracting this information from fluvially dominated sedimentary sequences may inform past variations in soil OC turnover in response to anthropogenic and/or climate perturbations. In turn, monitoring riverine OC composition may help detect future climate-change-induced perturbations of soil OC turnover and stocks.

CO2 Electrolysis System under Industrially Relevant Conditions.

ConspectusCarbon dioxide emissions from consumption of fossil fuels have caused serious climate issues. Rapid deployment of new energies makes renewable energy driven CO2 electroreduction to chemical feedstocks and carbon-neutral fuels a feasible and cost-effective pathway for achieving net-zero emission. With the urgency of the net-zero goal, we initiated our research on CO2 electrolysis with emphasis on industrial relevance.The CO2 molecules are thermodynamically stable due to high activation energy of the two C═O bonds, and efficient electrocatalysts are required to overcome the sluggish dynamics and competitive hydrogen evolution reaction. The CO2 electrocatalysts that we have explored include molecular catalysts and nanostructured catalysts. Molecular catalysts are centered on earth abundant elements such as Fe and Co for catalyzing CO2 reduction, and using Fe catalysts, we proposed an amidation strategy for reduction of CO2 to methanol, bypassing the inactive formate pathway. For nanostructured catalysts, we developed a carbon enrichment strategy using nitrogen-rich nanomaterials for selective CO2 reduction.Direct CO2 electroreduction from the flue gas stream represents the "holy grail" in the field, because typical CO2 concentration in flue gas is only 6-15%, posing a significant challenge for CO2 electrolysis. On the other hand, direct electroreduction of CO2 in the flue gas eliminates the carbon capture process and simplifies the overall carbon capture and utilization (CCU) scheme. However, direct flue gas reduction is frustrated by the reactive oxygen (5-8%), low CO2 concentration (6-15%), and potentially toxic impurities. Surface CO2 enrichment catalysts with high O2 tolerance could be viable for achieving direct CO2 electroreduction for decarbonization of flue gas.In addition to the electrocatalysts, the incorporation of catalysts into the electrolyzer and development of a suitable process was also investigated to meet industrial demands. A membrane electrode assembly (MEA) is a zero-gap configuration with cathode and anode catalysts coated on either side of an ion exchange membrane. We adopted the MEA configuration due to the structural simplicity, low ohmic resistance, and high efficiency. The electrode factors (for example, membrane type, catalyst layer porosity, and MEA fabrication method) and the electrolyzer factors (for example, flow channels, gas diffusion layer) are critical to highly efficient operation. We separately developed an anion-exchange membrane-based system for CO production and cation-exchange membrane-based system for formate production. The optimized electrolyzer configuration can generate uniform current and voltage distribution in a large-area electrolyzer and operate using an industrial CO2 stream. The optimized process was developed with the targets of long-term continuous operation and no electrolyte consumption.

An electric-field-driven ferroelectric nanodomain structure and its multilevel data storage application.

Solid-state multilevel data storage devices based on ferroelectric materials possess significant potential for use as artificial synapses in building biomimetic neural networks with low energy consumption and efficient data processing capabilities. To enable multilevel data storage, precise control of the ferroelectric domain through voltage pulses is essential. In this study, we investigate the manipulation of ferroelectric nanodomain structures using a nanotip and demonstrate their evolution under controlled application of electric pulses with varying strength and duration. The results highlight the differences in electric-field-driven ferroelectric nanodomain structures between (001)-/(101)- and (111)-oriented PbZr0.2Ti0.8O3 thin films. Interestingly, the latter exhibits highly anisotropic domain wall motion characteristics. The (111)-oriented PbZr0.2Ti0.8O3/SrRuO3 heterostructure demonstrates the best performance in increasing the domain radius with respect to electric pulse strength and duration. It shows at least three resistance states with a high switching ratio, making it a promising candidate for multilevel data storage applications. Additionally, the self-reversal rates of upward and downward domains differ and must be considered in designing and implementing multilevel data storage systems for stability and effectiveness. These findings reveal the potential of ferroelectric nanodomain structures for data storage and pave the way for nanotip-controlled artificial synapses.

A general strategy to stabilize 1T-MoS2 using MXene heterostructures and unlock its hydrogen evolution reaction capabilities.

The two-dimensional (2D) metallic phase of MoS2, 1T-MoS2, has extraordinary electrical conductivity in contrast to the common 2D semiconducting phase, 2H-MoS2. However, the thermodynamic instabilities of 1T-MoS2 hinder its application. In this work, we investigate the possibilities of stabilizing 1T-MoS2 through heterostructure design using first-principles calculations. We found that MXene-based heterostructures could hamper phase transitions from 1T-MoS2 to 2H-MoS2 enabled by a larger phase transition kinetic energy barrier. Based on this finding, we propose a general and effective strategy for stabilizing 1T-MoS2, that is, building heterostructures using 1T-MoS2 and oxygen-functionalized MXenes. Besides, we have also observed that due to the occurrence of electron transfer in the heterostructure, 1T-MoS2 in the heterostructure exhibits improved hydrogen adsorption free energy and more active sites compared to the monolayer 1T-MoS2. These findings provide guidance for promoting and developing 1T-MoS2 for practical applications. In addition, the proposed heterostructure design strategy could inspire the study of phase transition behaviors and electrochemical properties of materials using interfaces.

Recent water-level fluctuations, future trends and their eco-environmental impacts on Lake Qinghai.

The water level of Lake Qinghai, the largest lake on the Qinghai-Tibetan Plateau, has increased continuously, at an average speed of 0.21 m per year since 2005, causing a rapid expansion of the lake area. We investigated the hydrological processes of Lake Qinghai and the surrounding watershed that have influenced water level and lake area from 1956 to 2019. Relationships among water level, climate change and human activities were also assessed. Water level and lake area were positively correlated with precipitation and runoff into the lake, and negatively correlated with evaporation. Climate change factors including precipitation and runoff were the primary causes of lake level change, whereas human activities, including variation in a human footprint index, land use, and grassland irrigation, were secondary factors. A time series model forecasted that from 2020 to 2050 water levels will increase further by 2.45 m. Although this increase in water level may have some benefits, such as reduced local desertification, the expansion of lake area will continue to flood low beaches, pasture lands, near shore infrastructure and roads, and impact tourism locations. However, continued water level rise may also have negative ecological effects, such as reduce habitat of seasonal birds and reduced water quality due to erosion and sediment resuspension in shallow nearshore lake areas. Local stakeholders, government authorities, and scientists should give greater attention to anticipated changes in water level, and further ecological studies and infrastructure adaptation measures should be implemented.

Differences in the dynamic evolution of surface crack widths at different locations in the trench slope area and the mechanisms: a case study.

Coal seams were buried extremely shallowly in the trench slope area, which is prone to inducing surface cracks, seriously threatening the surface environment and mine safety production. The development of surface mining cracks varies at different locations in the trench slope area. In this research, we aimed to study the dynamic characteristics and laws of surface crack widths at different mining locations in the trench slope area and reveal the evolution mechanism of surface crack widths. Taking the 125,203 working face in Anshan Coal Mine in Shaanxi Province, China, as the geological prototype, we analyzed the full-cycle dynamic change law and planar distribution law of the surface crack widths in the trench slope area by combining the unmanned aerial vehicle remote sensing technology and field actual measurements and revealed the dynamic evolution mechanism of surface mining cracks in the trench area. The research results showed that the dynamic changes of surface crack widths varied at different locations of the slope. The surface crack width in the downslope area increased first and then stabilized with the advance of the working surface; the crack width at the bottom of the trench shows the dynamic change characteristic of increasing-decreasing-slightly increasing-stabilizing with the continuous advance of the working surface. The surface crack width in the upslope area showed the dynamic change of increasing-decreasing-stabilizing with the continuous advance of the working surface. Influenced by the surface morphology, the development mechanisms of surface mining cracks were different. The research results can provide practical guidance for selecting the best treatment time for surface cracks in different areas.

Unraveling the Oxidation Behaviors of MXenes in Aqueous Systems by Active-Learning-Potential Molecular-Dynamics Simulation.

MXenes are 2D materials with great potential in various applications. However, the degradation of MXenes in humid environments has become a main obstacle in their practical use. Here we combine deep neural networks and an active learning scheme to develop a neural network potential (NNP) for aqueous MXene systems with ab initio precision but low cost. The oxidation behaviors of super large aqueous MXene systems are investigated systematically at nanosecond timescales for the first time. The oxidation process of MXenes is clearly displayed at the atomic level. Free protons and oxides greatly inhibit subsequent oxidation reactions, leading to the degree of oxidation of MXenes to exponentially decay with time, which is consistent with the oxidation rate of MXenes measured experimentally. Importantly, this computational study represents the first exploration of the kinetic process of oxidation of super-sized aqueous MXene systems. It opens a promising avenue for the future development of effective protection strategies aimed at controlling the stability of MXenes.

ARRDC3 polymorphisms may affect the risk of glioma in Chinese Han.

This study ascertained to explore the potential contribution of ARRDC3 polymorphisms in the risk and prognosis of glioma. One thousand sixty-one patients and healthy controls were conducted to assess whether ARDC3 polymorphism was associated with glioma risk and prognosis. Four sites in ARRDC3 were selected and genotyped in MassARRAY platform. The calculated odd ratios and 95% confidence intervals from logistic regression were applied for risk assessment. The relationship between ARRDC3 variants and glioma prognosis was evaluated using log-rank test, Kaplan-Meier analysis, and so on. Also, false-positive report probability (FPRP) and statistical power were also assessed. Our findings suggested the negative role of ARRDC3 polymorphisms in the glioma risk. We also found the effect of candidate SNPs in ARRDC3 on the susceptibility to glioma was dependent on the age, gender, and histology of glioma patients. The results suggested that the genetic polymorphisms of ARRDC3 were related to an increased risk of glioma.

MiR-218 Targeted Regulation of Robol Expression Regulates Proliferation, Invasion and Migration of Glioma Cells.

In recent years, more and more researches has focused on "molecular targeted therapy" for basic genes and regulatory cells, but the effect is not ideal. Therefore, the discovery of new molecular targets with diagnostic and therapeutic significance can not only lay a solid foundation for molecular diagnosis and classification of lesions but also contribute to targeted therapy of glioma. This study aimed to discover the molecular mechanism of mir-218 targeting the regulation of robol expression on proliferation, invasion and migration of glioma cells and to provide a theoretical and experimental basis for finding therapeutic targets of glioma. The purpose of this study was to investigate the effect of mir-218 on gliomas by using the method of control experiment. The results showed that the number of gliomas under the action of mir-218 decreased from about 150 to about 80, and the number would tend to a fixed value range over time. In the experiment, the data decreased from about 150 to nearly 20, and compared with the control group, the control of glioma cell proliferation was very excellent.

Single-atom catalyst of TM@D-silicene-an effective way to reduce N2 into ammonia.

Nowadays, the electrocatalytic nitrogen reduction reaction (NRR) still faces great challenges. It's significant to design the electrocatalysts with excellent activity and high selectivity. Herein, the 28 single atom catalysts of transition metal atoms anchored on defective silicene (TM@D-silicene) are designed for electrocatalytic ammonia synthesis under ambient conditions. Two independent screening schemes are proposed to screen the potential SAC candidate. The criteria of Ebin < 0 eV, ΔG*N2< -0.1 eV, ΔG*H > ΔG*N2, and the lowest ΔG*NNH in scheme I, as well as ΔG*N2< -0.1 eV, smaller G*NNH and larger G*NH2 in scheme II are utilized in the screening procedure. Finally, Cr@D-silicene is picked out since it performs well in the aspects of N2 adsorption, selectivity and catalytic activity of NRR. Moreover, the electronic properties are systematically investigated to clarify why the Cr@D-silicene is qualified for NRR from the perspective of the strong interaction between N2 and Cr, the continuous activation of the N2 molecule, charge transfer and distribution. This work provides a new idea for electrocatalytic ammonia synthesis by using single-atom catalysts.

Nitrogen reduction reaction on single cluster catalysts of defective PC6-trimeric or tetrameric transition metal.

The traditional Haber-Bosch method of ammonia (NH3) synthesis has low production efficiency and can lead to greenhouse gas emission due to high temperature and pressure dependent reactions. Hence, the nitrogen reduction reaction (NRR) in a mild environment has been developed. However, the inert NN triple bond and the competition with the hydrogen evolution reaction (HER) limit its wide application. In order to find an effective way of reducing N2 into NH3, in this work, PC6 monolayers with good electro-optical properties and eight transition metals (V, Cr, Mn, Fe, Co, Ni, Cu, Zn) are chosen to construct PC6-TM3 and PC6-TM4 single cluster catalysts (SCCs), which are proved to have low overpotential, multiple active-sites and superior activity. The thermodynamic stability, N2 adsorption, reaction paths, selectivity for the NRR and catalytic mechanism are systematically investigated. (PC6-Co3, PC6-Fe4)/(PC6-V3, PC6-Cr3)/(PC6-V4, PC6-Mn4) prefer to adsorb N2 rather than H in the end-on/side-on I/side-on III mode. PC6-Fe4 and PC6-Cr3 are finally screened out which have excellent catalytic activity with an overpotential of -0.46 V and -0.26 V in the consecutive path of side-on III and I modes, respectively. Moreover, both of them have 100% faradaic efficiency and present high selectivity for the NRR. The catalytic mechanism is elucidated by discussing the electronic properties of PC6-Cr3, where the back-donation behaviors of Cr atoms play an important role during the formation of NH3. This research may provide theoretical guidance for finding potential NRR catalysts with excellent performance and high selectivity.

Dihydromyricetin Attenuates High-Intensity Exercise-Induced Intestinal Barrier Dysfunction Associated with the Modulation of the Phenotype of Intestinal Intraepithelial Lymphocytes.

BACKGROUND: Exercise-induced gastrointestinal syndrome (GIS) has symptoms commonly induced by strenuous sports. The study aimed to determine the effect of dihydromyricetin (DHM) administration on high-intensity exercise (HIE)-induced intestinal barrier dysfunction and the underlying mechanism involved with intestinal intraepithelial lymphocytes (IELs). METHODS: The HIE model was established with male C57BL/6 mice using a motorized treadmill for 2 weeks, and DHM was given once a day by oral gavage. After being sacrificed, the small intestines of the mice were removed immediately. RESULTS: We found that DHM administration significantly suppressed HIE-induced intestinal inflammation, improved intestinal barrier integrity, and inhibited a HIE-induced increase in the number of IELs and the frequency of CD8αα+ IELs. Meanwhile, several markers associated with the activation, gut homing and immune functions of CD8αα+ IELs were regulated by DHM. Mechanistically, luciferase reporter assay and molecular docking assay showed DHM could activate the aryl hydrocarbon receptor (AhR). CONCLUSIONS: These data indicate that DHM exerts a preventive effect against HIE-induced intestinal barrier dysfunction, which is associated with the modulation of the quantity and phenotype of IELs in the small intestine. The findings provide a foundation to identify novel preventive strategies based on DHM supplementation for HIE-induced GIS.

Properties and regulation of Gly-Sar uptake and transport in bovine intestinal epithelial cells.

Intestinal absorption of peptides is vital for the overall health and productivity of dairy cows. This study investigated the regulation, uptake and transport of dipeptides in bovine intestinal epithelial cells (BIECs). We also evaluated the effects of time, pH, concentration of the dipeptides, temperature, presence of diethylpyrocarbonate (DEPC)-an inhibitor of PepT1, and other dipeptides (Met-Met, Lys-Lys or Met-Lys), on the uptake and transport of Gly-Sar-FITC, which was a common fluorophore-labelled dipeptide. Under controlled experiments, BIECs were treated with 25 µM LY294002 (a phosphatidylinositol 3-kinase (PI3K) inhibitor) and 25 µM Perifosine (a protein kinase B (AKT) inhibitor). The subsequent expression of PepT1 in the BIECs was assessed by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting. It was found that the uptake and transport of Gly-Sar-FITC were significant high at 37℃ than that at 4℃. The optimal pH for transport and uptake of Gly-Sar-FITC was 6.0-6.5, whereas the two properties decreased significantly in the presence of DEPC, Met-Met, Lys-Lys and Met-Lys (p < 0.05). The apical-to-basolateral transport was also found to be significantly higher than the reverse transport (p < 0.05). PI3K and AKT inhibitors were found to significantly suppress the expression of PepT1, thus impairing uptake and transport of Gly-Sar-FITC. Findings of this study thus suggest that the uptake and transport of Gly-Sar-FITC in BIECs are mediated by PepT1, and the PI3K/AKT signalling pathway regulates the absorption of small peptides.

Genetic variants of CYP4F12 gene are associated with glioma susceptibility.

Glioma is a common and fatal primary malignant tumor of the central nervous system, and its prognosis is poor. To determine the susceptibility markers of gliomas in Chinese population we conducted a genome-wide association study (GWAS) of glioma in the Han Chinese population, with a total of 485 glioma cases and 485 controls. Genotyping was conducted using the Applied Biosystems Axiom Precision Medicine Diversity Array. Besides, we carried out imputation using IMPUTE 2.0 software, and the 1000 Genomes Phase 3 was used as the reference panel. The logistic regression model was used to analyze the association of each SNP with glioma risk, assuming an additive genetic model, which was implemented in PLINK version 1.9. Odds ratio (OR) and 95% confidence interval (CI) were estimated from logistic regression analysis with adjustment for age and gender. The results revealed that the SNP (rs688755) in the exon region of CYP4F12 at 19p13.12 reached genome-wide significance associated with gliomas (P = 2.35 × 10-8 , OR = 3.55, 95% CI = 2.20-5.74). Our findings provide deeper insight into the genetic contribution to glioma in different populations.

Degradation and Aging of Terrestrial Organic Carbon within Estuaries: Biogeochemical and Environmental Implications.

Estuaries are action zones for organic carbon (OC) degradation and aging. These processes influence the nature of terrestrial OC (OCterr) export and the magnitude of OCterr burial in marginal seas, with important environmental implications such as CO2 release and hypoxia. In this study, we determined the contents and carbon isotopic compositions (13C and 14C) of bulk OC and fatty acids (FAs) as well as the sedimentological characteristics of suspended particulate matter (SPM) samples collected from two sites over four seasons and of surface sediment samples from three sites in the Pearl River estuary (PRE) to evaluate processes controlling OCterr degradation and aging along an estuarine gradient. We found that the abundance-weighted average C24-32FA 14C ages increased by an average of ∼1170 years for SPM and by an average of ∼3440 years in PR/PRE sediments, along the ∼60 km PRE transect. These increases in the FA age coincided with an 86% decrease in the corresponding mineral surface area-normalized FA loading along the sediment transport pathway, implying that selective degradation of labile and younger OC resulted in apparent OC aging. These measurements reveal an important shift in the nature of OC, with implications for biogeochemical cycling within estuaries and for regional environmental changes.

A WiFi scanner in conjunction with disposable multiplex paper assay for the quantitation of disease markers in blood plasma.

Herein we report a quantitative, multiplex assay for disease markers in plasma based on an integrated setup of a portable scanner and a disposable paper-based analytical device (PAD). The quantitative analysis relies on the digital colorimetric reading of the three-layer PAD with 30 assay sites for performing respective chromogenic reactions for plasma uric acid, glucose, and triglyceride, which are considered as important risk factors for cardiovascular diseases. A portable scanner with WiFi transmission capability was used to produce high-quality color images of the PADs and wirelessly transfer them to a smartphone or other mobile devices for data processing. The concentrations of biomarkers in both standard solutions and plasma samples can be directly obtained using a custom-designed smartphone app that is also capable of constructing calibration curves. The detection limits of uric acid, glucose, and triglyceride were determined to be 0.50 mg/dL, 0.84 mmol/L, and 14 mg/dL, respectively, which are below the normal limits and adequate for clinical validation. Owing to the distinct advantages-simple, portable, and cost-effective-this mobile assay protocol can be used for point-of-care (POC) settings or resource-limited situations, and potentially for the diagnosis and prevention of infectious diseases.

Validation of radiographic quality of simulation software - ImaSim.

BACKGROUND: Virtual radiographic simulation has been found educationally effective for students to practice their clinical examinations remotely or online. A free available virtual simulator-ImaSim has received particular attention for radiographic science education because of its portability, free of charge and no constrain of location and physical facility. However, it lacks evidence to validate this virtual simulation software to faithfully reproduce radiographs comparable to that taken from a real X-ray machine to date. OBJECTIVE: To evaluate image quality of the virtual radiographs produced by the ImaSim. Thus, the deployment of this radiographic simulation software for teaching and experimental studying of radiography can be justified. METHODS: A real medical X-ray examination machine is employed to scan three standard QC phantoms to produce radiographs for comparing to the corresponding virtual radiographs generated by ImaSim software. The high and low range of radiographic contrast and comprehensive contrast-detail performance are considered to characterize the radiographic quality of the virtual simulation software. RESULTS: ImaSim software can generate radiographs with a contrast ranging from 30% to 0.8% and a spatial resolution as low as 0.6mm under the selected exposure setting condition. The characteristics of contrast and spatial resolution of virtual simulation generally agree with that of real medical X-ray examination machine. CONCLUSION: ImaSim software can be used to simulate a radiographic imaging process to generate radiographs with contrast and detail detectability comparable to those produced by a real X-ray imaging machine. Therefore, it can be adopted as a flexible educational tool for proof of concept and experimental design in radiography.