Evolution of dislocation substructures in metals via high-strain-rate nanoindentation.

Deformation at high strain rates often results in high stresses on many engineering materials, potentially leading to catastrophic failure without proper design. High-strain-rate mechanical testing is thus needed to improve the design of future structural materials for a wide range of applications. Although several high-strain-rate mechanical testing techniques have been developed to provide a fundamental understanding of material responses and microstructural evolution under high-strain-rate deformation conditions, these tests are often very time consuming and costly. In this work, we utilize a high-strain-rate nanoindentation testing technique and system in combination with transmission electron microscopy to reveal the deformation mechanisms and dislocation substructures that evolve in pure metals from low (10-2 s-1) to very high indentation strain rates (104 s-1), using face-centered cubic aluminum and body-centered cubic molybdenum as model materials. The results help to establish the conditions under which micro- and macro-scale tests can be compared with validity and also provide a promising pathway that could lead to accelerated high-strain-rate testing at substantially reduced costs.

TIMELESS promotes reprogramming of glucose metabolism in oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC), the predominant malignancy of the oral cavity, is characterized by high incidence and low survival rates. Emerging evidence suggests a link between circadian rhythm disruptions and cancer development. The circadian gene TIMELESS, known for its specific expression in various tumors, has not been extensively studied in the context of OSCC. This study aims to explore the influence of TIMELESS on OSCC, focusing on cell growth and metabolic alterations. METHODS: We analyzed TIMELESS expression in OSCC using western blot, immunohistochemistry, qRT-PCR, and data from The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE). The role of TIMELESS in OSCC was examined through clone formation, MTS, cell cycle, and EdU assays, alongside subcutaneous tumor growth experiments in nude mice. We also assessed the metabolic impact of TIMELESS by measuring glucose uptake, lactate production, oxygen consumption, and medium pH, and investigated its effect on key metabolic proteins including silent information regulator 1 (SIRT1), hexokinase 2 (HK2), pyruvate kinase isozyme type M2 (PKM2), recombinant lactate dehydrogenase A (LDHA) and glucose transporter-1 (GLUT1). RESULTS: Elevated TIMELESS expression in OSCC tissues and cell lines was observed, correlating with reduced patient survival. TIMELESS overexpression enhanced OSCC cell proliferation, increased glycolytic activity (glucose uptake and lactate production), and suppressed oxidative phosphorylation (evidenced by reduced oxygen consumption and altered pH levels). Conversely, TIMELESS knockdown inhibited these cellular and metabolic processes, an effect mirrored by manipulating SIRT1 levels. Additionally, SIRT1 was positively associated with TIMELESS expression. The expression of SIRT1, HK2, PKM2, LDHA and GLUT1 increased with the overexpression of TIMELESS levels and decreased with the knockdown of TIMELESS. CONCLUSION: TIMELESS exacerbates OSCC progression by modulating cellular proliferation and metabolic pathways, specifically by enhancing glycolysis and reducing oxidative phosphorylation, largely mediated through the SIRT1 pathway. This highlights TIMELESS as a potential target for OSCC therapeutic strategies.

Combining Mefloquine with an Mcl-1 Inhibitor as a Novel Therapeutic Strategy for the Treatment of Nasopharyngeal Carcinoma.

Considering the established pharmacokinetics and toxicity profiles, drug repurposing has emerged as an alternative therapeutic approach for treating cancer. Mefloquine has previously demonstrated inhibitory effects on multiple cancer types. This study aims to explore the impact of mefloquine on nasopharyngeal carcinoma (NPC). We found that mefloquine, at pharmacologically achievable concentrations, displayed anti-NPC activity while sparing normal counterparts. Mefloquine inhibits proliferation and induces death by reducing the levels of Cyclin A2, Bcl-2, and Bcl-xL. Intriguingly, we observed an increase in the levels of the anti-apoptotic protein Mcl-1. Mefloquine exerts its effects on NPC cells by inducing lysosomal-mediated ROS production, and the heightened expression of Mcl-1 is a consequence of ROS generation in mefloquine-treated NPC cells. The combination of an Mcl-1 inhibitor with mefloquine synergistically inhibits NPC growth in mice without causing substantial toxicity. These findings demonstrate the effectiveness and limited toxicity of mefloquine as a monotherapy and in combination with an Mcl-1 inhibitor. Our research underscores the promise of the mefloquine and Mcl-1 inhibitor combination as a potential treatment for NPC. Additionally, the elevation of Mcl-1 is a compensatory response in cells exposed to oxidative stress, offering a potential target to overcome resistance induced by pro-oxidant therapies.

Fast shadow casting algorithm in analytical polygon-based computer-generated holography.

Shadow casting is essential in computer graphics, which can significantly enhance the reality of rendered images. However, shadow casting is rarely studied in polygon-based computer-generated holography (CGH) because state-of-art triangle-based occlusion handling methods are too complicated for shadow casting and unfeasible for complex mutual occlusion handling. We proposed a novel drawing method based on the analytical polygon-based CGH framework and achieved Z-buffer-based occlusion handling instead of the traditional Painter's algorithm. We also achieved shadow casting for parallel and point light sources. Our framework can be generalized to N-edge polygon (N-gon) rendering and accelerated using CUDA hardware, by which the rendering speed can be significantly enhanced.

Real-time computer-generated integral imaging light field displays: revisiting the point retracing rendering method from a signal processing perspective.

Integral imaging light field displays (InIm-LFDs) can provide realistic 3D images by showing an elemental image array (EIA) under a lens array. However, it is always challenging to computationally generate an EIA in real-time with entry-level computing hardware because the current practice that projects many viewpoints to the EIA induces heavy computations. This study discards the viewpoint-based strategy, revisits the early point retracing rendering method, and proposes that InIm-LFDs and regular 2D displays share two similar signal processing phases: sampling and reconstructing. An InIm-LFD is demonstrated to create a finite number of static voxels for signal sampling. Each voxel is invariantly formed by homogeneous pixels for signal reconstructing. We obtain the static voxel-pixel mapping through arbitrarily accurate raytracing in advance and store it as a lookup table (LUT). Our EIA rendering method first resamples input 3D data with the pre-defined voxels and then assigns every voxel's value to its homogeneous pixels through the LUT. As a result, the proposed method reduces the computational complexity by several orders of magnitude. The experimental rendering speed is as fast as 7 to 10 ms for a full-HD EIA frame on an entry-level laptop. Finally, considering a voxel may not be perfectly integrated by its homogeneous pixels, called the sampling error, the proposed and conventional viewpoint-based methods are analyzed in the Fourier domain. We prove that even with severe sampling errors, the two methods negligibly differ in the output signal's frequency spectrum. We expect the proposed method to break the long-standing tradeoff between rendering speed, accuracy, and system complexity for computer-generated integral imaging.

Compact dual-focal augmented reality head-up display using a single picture generation unit with polarization multiplexing.

The augmented reality head-up display (AR-HUD) attracts increasing attention. It features multiple focal planes to display basic and AR information, as well as a wider field of view (FOV). Using two picture generation units (PGUs) to create dual-focal AR-HUDs leads to expanded size, increased cost, and reduced reliability. Thus, we previously proposed an improved solution by dividing one PGU into two partitions that were separately imaged into two virtual images with an optical relay system. However, the resolution of the PGU was halved for either virtual image. Regarding the drawbacks, this paper proposes a dual-focal AR-HUD using one PGU and one freeform mirror. Either virtual image utilizes the full resolution of the PGU through polarization-multiplexing. By performing optical design optimization, high image quality, except for the distortion, is achieved in an eyebox of 130 by 60 mm for far (10 m, 13° by 4°) and near (2.5 m, 10° by 1°) images. Next, we propose a distortion correction method by directly inputting the distorted but clear images acquired in the design stage into the real HUD with an inversed optical path. The proposed optical architecture enables a compact system volume of 9.5 L, close to traditional single-focal HUDs. Finally, we build an AR-HUD prototype, where a polarizing reflective film and a twisted nematic liquid crystal cell achieve polarization-multiplexing. The expected image quality of the two virtual images is experimentally verified.

Universal cover-time distributions of random motion in bounded granular gases.

The exhaustive random exploration of a complex domain is a fundamental issue in many natural, social, and engineering systems. The key characterizing quantity is the cover time, which is the time to visit every site in the system. One prototypical experimental platform is the confined granular gas, where the random motion of granular particles mimics the wandering of random walkers in a confined region. Here, we investigate the cover-time distribution of the random motion of tracer particles in granular gases confined in four containers to account for different boundary and angle effects and examine whether the cover time of the heterogeneous random motion of the granular gases can be rescaled into the universal Gumbel distribution according to a recent theory [Dong et al., arXiv:2210.05122 (2022)]. It is found that for long cover times, the experimental results are in full accord, while for short cover times, the agreement is reasonable, with noticeable deviations that can be attributed to spatial correlations of the sites in the covering process. Our results, thus, call for further theoretical investigations in order to take into full account these nonideal issues.

UWB Localization Based on Improved Robust Adaptive Cubature Kalman Filter.

Aiming at the problems of Non-Line-of-Sight (NLOS) observation errors and inaccurate kinematic model in ultra-wideband (UWB) systems, this paper proposed an improved robust adaptive cubature Kalman filter (IRACKF). Robust and adaptive filtering can weaken the influence of observed outliers and kinematic model errors on filtering, respectively. However, their application conditions are different, and improper use may reduce positioning accuracy. Therefore, this paper designed a sliding window recognition scheme based on polynomial fitting, which can process the observation data in real-time to identify error types. Simulation and experimental results indicate that compared to the robust CKF, adaptive CKF, and robust adaptive CKF, the IRACKF algorithm reduces the position error by 38.0%, 45.1%, and 25.3%, respectively. The proposed IRACKF algorithm significantly improves the positioning accuracy and stability of the UWB system.

Multiple Helicenes Defected by Heteroatoms and Heptagons with Narrow Emissions and Superior Photoluminescence Quantum Yields.

The incorporation of heteroatoms and/or heptagons as the defects into helicenes expands the variety of chiroptical materials with novel properties. However, it is still challenging to construct novel boron-doped heptagon-containing helicenes with high photoluminescence quantum yields (PLQYs) and narrow full-width-at-half-maximum (FWHM) values. We report an efficient and scalable synthesis of a quadruple helicene 4Cz-NBN with two nitrogen-boron-nitrogen (NBN) units and a double helicene 4Cz-NBN-P1 bearing two NBN-doped heptagons, the latter could be formed via a two-fold Scholl reaction of the former. The helicenes 4Cz-NBN and 4Cz-NBN-P1 exhibit excellent PLQYs up to 99 % and 65 % with narrow FWHM of 24 nm and 22 nm, respectively. The emission wavelengths are tunable via stepwise titration experiments of 4Cz-NBN-P1 toward fluoride, enabling distinguished circularly polarized luminescence (CPL) from green, orange (4Cz-NBN-P1-F1) to yellow (trans/cis-4Cz-NBN-P1-F2) with near-unity PLQYs and broader circular dichroism (CD) ranges. The five structures of the aforementioned four helicenes were confirmed by single crystal X-ray diffraction analysis. This work provides a novel design strategy for construction of non-benzenoid multiple helicenes exhibiting narrow emissions with superior PLQYs.

CircNTNG1 inhibits renal cell carcinoma progression via HOXA5-mediated epigenetic silencing of Slug.

BACKGROUND: Recent studies have identified that circular RNAs (circRNAs) have an important role in cancer via their well-recognized sponge effect on miRNAs, which regulates a large variety of cancer-related genes. However, only a few circRNAs have been well-studied in renal cell carcinoma (RCC) and their regulatory function remains largely elusive. METHODS: Bioinformatics approaches were used to characterize the differentially expressed circRNAs in our own circRNA-sequencing dataset, as well as two public circRNA microarray datasets. CircNTNG1 (hsa_circ_0002286) was identified as a potential tumor-suppressing circRNA. Transwell assay and CCK-8 assay were used to assess phenotypic changes. RNA pull-down, luciferase reporter assays and FISH experiment were used to confirm the interactions among circNTNG1, miR-19b-3p, and HOXA5 mRNA. GSEA was performed to explore the downstream pathway regulated by HOXA5. Immunoblotting, chromatin immunoprecipitation, and methylated DNA immunoprecipitation were used to study the mechanism of HOXA5. RESULTS: In all three circRNA datasets, circNTNG1, which was frequently deleted in RCC, showed significantly low expression in the tumor group. The basic properties of circNTNG1 were characterized, and phenotype studies also demonstrated the inhibitory effect of circNTNG1 on RCC cell aggressiveness. Clinically, circNTNG1 expression was associated with RCC stage and Fuhrman grade, and it also served as an independent predictive factor for both OS and RFS of RCC patients. Next, the sponge effect of circNTNG1 on miR-19b-3p and the inhibition of HOXA5 by miR-19b-3p were validated. GSEA analysis indicated that HOXA5 could inactivate the epithelial-mesenchymal transition (EMT) process, and this inactivation was mediated by HOXA5-induced SNAI2 (Slug) downregulation. Finally, it was confirmed that the Slug downregulation was caused by HOXA5, along with the DNA methyltransferase DNMT3A, binding to its promoter region and increasing the methylation level. CONCLUSIONS: Based on the experimental data, in RCC, circNTNG1/miR-19b-3p/HOXA5 axis can regulate the epigenetic silencing of Slug, thus interfering EMT and metastasis of RCC. Together, our findings provide potential biomarkers and novel therapeutic targets for future study in RCC.

High speed time-of-flight displacement measurement based on dual-comb electronically controlled optical sampling.

We demonstrate a direct time-of-flight approach that utilizes dual-comb electronically controlled optical sampling (ECOPS) to measure small displacements. ECOPS is enabled by electrically controlling the repetition rate of one laser via an intracavity electric-optical modulator (EOM). The acquisition rate is set by the EOM modulation frequency, which is much higher than commonly used asynchronous optical sampling (ASOPS). In a proof-of-principle experiment, an 80-kHz acquisition rate is obtained with a pair of ∼105 MHz repetition rate Er-fiber lasers. At an average time of 30 ms, a measurement precision evaluated with Allan deviation reaches 26.1 nm for a 40-µm static displacement. In a dynamic measurement, a 500-Hz sinusoidal vibration with 15 µm amplitude has also been identified. The high-precision and high-speed displacement measurement technique can be potentially used in 3D surface profilometry of microelectronic step-structures and real-time monitoring of high frequency mechanical vibrations, etc.

Moniezia benedeni infection enhances neuromedin U (NMU) expression in sheep (Ovis aries) small intestine.

BACKGROUND: Neuromedin U (NMU) plays an important role in activating the group 2 innate lymphoid cells (ILC2s) and initiating the host's anti-parasitic immune responses. It is aimed to explore the distribution characteristics of NMU in the sheep small intestine and the influence of Moniezia benedeni infection on them. In the present study, the pET-28a-NMU recombinant plasmids were constructed, and Escherichia coli. BL21 (DE3) were induced to express the recombinant protein. And then, the rabbit anti-sheep NMU polyclonal antibody was prepared and immunofluorescence staining was performed with it. The expression levels of NMU in the intestine of normal and Moniezia benedeni-infected sheep were detected by ELISA. RESULTS: The results showed that the molecular weight of the obtained NMU recombinant protein was consistent with the expected molecular (13 kDa) and it was expressed in the form of inclusion body. The titer and specificity of obtained rabbit anti-sheep NMU polyclonal antibody were good. The results of immunofluorescence analysis showed that the nerve fibers which specifically expressed NMU mainly extended from the ganglion in the submucosal to lamina propria (LP) in the sheep small intestine, and the expression level was relatively high; especially on the nerve fibers of LP around the intestinal glands. The expression levels were gradually increased from the duodenum to the ileum, and the levels in the jejunum and ileum were significantly higher than that in the duodenum (P < 0.05). In addition, scattered NMU positive cells were distributed in the epithelium of the jejunal crypts. Moniezia benedeni infection increased the expression of NMU in each intestinal segment, especially in the jejunum and ileum there were significant increase (P < 0.05). CONCLUSIONS: It was suggested that Moniezia benedeni infection could be detected by the high expression of NMU in sheep enteric nervous, and which laid the foundation for further studies on whether NMU exerts anti-parasitic immunity by activating ILC2s. In addition, NMU was expressed in some intestinal gland epitheliums, which also provided a basis for studying its roles in regulation of the immune homeostasis. The present study laid the foundation for further revealing the molecular mechanism of sheep's neural-immune interaction network perceiving the colacobiosis of parasites.

Beyond Boolean: Ternary networks and dynamics.

Boolean networks introduced by Kauffman, originally intended as a prototypical model for gaining insights into gene regulatory dynamics, have become a paradigm for understanding a variety of complex systems described by binary state variables. However, there are situations, e.g., in biology, where a binary state description of the underlying dynamical system is inadequate. We propose random ternary networks and investigate the general dynamical properties associated with the ternary discretization of the variables. We find that the ternary dynamics can be either ordered or disordered with a positive Lyapunov exponent, and the boundary between them in the parameter space can be determined analytically. A dynamical event that is key to determining the boundary is the emergence of an additional fixed point for which we provide numerical verification. We also find that the nodes playing a pivotal role in shaping the system dynamics have characteristically distinct behaviors in different regions of the parameter space, and, remarkably, the boundary between these regions coincides with that separating the ordered and disordered dynamics. Overall, our framework of ternary networks significantly broadens the classical Boolean paradigm by enabling a quantitative description of richer and more complex dynamical behaviors.

Glyoxal damages human aortic endothelial cells by perturbing the glutathione, mitochondrial membrane potential, and mitogen-activated protein kinase pathways.

BACKGROUND: Exposure to glyoxal, the smallest dialdehyde, is associated with several diseases; humans are routinely exposed to glyoxal because of its ubiquitous presence in foods and the environment. The aim of this study was to examine the damage caused by glyoxal in human aortic endothelial cells. METHODS: Cell survival assays and quantitative fluorescence assays were performed to measure DNA damage; oxidative stress was detected by colorimetric assays and quantitative fluorescence, and the mitogen-activated protein kinase pathways were assessed using western blotting. RESULTS: Exposure to glyoxal was found to be linked to abnormal glutathione activity, the collapse of mitochondrial membrane potential, and the activation of mitogen-activated protein kinase pathways. However, DNA damage and thioredoxin oxidation were not induced by dialdehydes. CONCLUSIONS: Intracellular glutathione, members of the mitogen-activated protein kinase pathways, and the mitochondrial membrane potential are all critical targets of glyoxal. These findings provide novel insights into the molecular mechanisms perturbed by glyoxal, and may facilitate the development of new therapeutics and diagnostic markers for cardiovascular diseases.

Controlled generation of self-sustained oscillations in complex artificial neural networks.

Spatially distinct, self-sustained oscillations in artificial neural networks are fundamental to information encoding, storage, and processing in these systems. Here, we develop a method to induce a large variety of self-sustained oscillatory patterns in artificial neural networks and a controlling strategy to switch between different patterns. The basic principle is that, given a complex network, one can find a set of nodes-the minimum feedback vertex set (mFVS), whose removal or inhibition will result in a tree-like network without any loop structure. Reintroducing a few or even a single mFVS node into the tree-like artificial neural network can recover one or a few of the loops and lead to self-sustained oscillation patterns based on these loops. Reactivating various mFVS nodes or their combinations can then generate a large number of distinct neuronal firing patterns with a broad distribution of the oscillation period. When the system is near a critical state, chaos can arise, providing a natural platform for pattern switching with remarkable flexibility. With mFVS guided control, complex networks of artificial neurons can thus be exploited as potential prototypes for local, analog type of processing paradigms.

Revealing horizontal and vertical variation of soil organic carbon, soil total nitrogen and C:N ratio in subtropical forests of southeastern China.

Soil organic carbon (SOC) and total nitrogen (STN) are crucial soil quality indicators in a forest ecosystem. Their cycling processes and interactions have a key impact on the plants productivity, potential carbon sequestration and stability of the terrestrial ecosystem. In this study, soil profile samples (0-100 cm) were collected from 906 plots of typical subtropical forest in Zhejiang Province, southeastern China. Moran's I, geostatistics and geographic information system (GIS) techniques were used to study the vertical and horizontal heterogeneity of SOC, STN and C:N ratio. The results indicated that the contents of SOC and STN clearly decreased with the soil depth increasing (from 0 to 10 cm layer to 60-100 cm layer). The spatial distributions of SOC and STN were consistent with the topography, showing a decreasing trend from southwest to northeast of Zhejiang Province. The results of ANOVA and correlation analyses indicated that the dominant tree species, elevation and Normalized Difference Vegetation Index (NDVI) were the key factors affecting SOC and STN contents. For the total 0-100 cm soil layer, the mean densities of SOC and STN were 108.53 Mg ha-1 and 0.08 Mg ha-1, respectively. The total stocks of SOC and STN were 877.19 Tg and 84.42 Tg. Approximately 65% SOC and 45% STN were belonged to the upper 30 cm soil layer, which was strongly related to the actual soil thickness. The results could provide critical information for forestry and environmental management related to C and N accumulations in subtropical forests of China.

Injury and Apoptosis in the Palatopharyngeal Muscle in Patients with Obstructive Sleep Apnea-Hypopnea Syndrome.

BACKGROUND This study aimed to elucidate the possible activity of the mitochondrial-mediated apoptotic pathway (MMAP) in obstructive sleep apnea-hypopnea syndrome (OSAHS). MATERIAL AND METHODS A control group, a mild OSAHS group, a moderate OSAHS group, and a severe OSAHS group were included. Masson staining, hematoxylin and eosin staining, and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay were performed to assess collagen fiber hyperplasia, pathological morphology, and cell apoptosis, respectively, in muscle samples. RESULTS In the OSAHS groups, the palatopharyngeal muscle fibers were larger, with apparent hypertrophy and increased elastic fiber content. The proportions of type I fibers were markedly higher in the control group than in the moderate and severe OSAHS groups (P<0.05). Moreover, apoptosis was significantly enhanced in the muscle cells of the OSAHS groups. The Bax expression levels gradually increased across the 4 groups (lowest in the control group and highest in the severe OSAHS group) (P<0.05); conversely, the p38 and p62 expression levels did not significantly differ among groups (P>0.05). CONCLUSIONS A decrease in the proportion of the different fiber types can result in collapse of the upper airway. The pathogenesis of OSAHS appears to involve muscle cell apoptosis via MMAP.

Scatter Enhanced Phase Contrast Microscopy for Discriminating Mechanisms of Active Nanoparticle Transport in Living Cells.

Understanding the uptake and transport dynamics of engineered nanomaterials (ENMs) by mammalian cells is an important step in designing next-generation drug delivery systems. However, to track these materials and their cellular interactions, current studies often depend on surface-bound fluorescent labels, which have the potential to alter native cellular recognition events. As a result, there is still a need to develop methods capable of monitoring ENM-cell interactions independent of surface modification. Addressing these concerns, here we show how scatter enhanced phase contrast (SEPC) microscopy can be extended to work as a generalized label-free approach for monitoring nanoparticle uptake and transport dynamics. To determine which materials can be studied using SEPC, we turn to Lorenz-Mie theory, which predicts that individual particles down to ∼35 nm can be observed. We confirm this experimentally, demonstrating that SEPC works for a variety of metal and metal oxides, including Au, Ag, TiO2, CeO2, Al2O3, and Fe2O3 nanoparticles. We then demonstrate that SEPC microscopy can be used in a quantitative, time-dependent fashion to discriminate between distinct modes of active cellular transport, including intracellular transport and membrane-assisted transport. Finally, we combine this technique with microcontact printing to normalize transport dynamics across multiple cells, allowing for a careful study of ensemble TiO2 nanoparticle uptake. This revealed three distinct regions of particle transport across the cell, indicating that membrane dynamics play an important role in regulating particle flow. By avoiding fluorescent labels, SEPC allows for a rational exploration of the surface properties of nanomaterials in their native state and their role in endocytosis and cellular transport.

Effects of antithrombotic therapy on bleeding after endoscopic submucosal dissection.

BACKGROUND AND AIMS: Bleeding is the most common adverse event after endoscopic submucosal dissection (ESD). Although several studies have reported on the use of antithrombotic agents and post-ESD bleeding, many issues remain controversial. We conducted a meta-analysis and systematic review to evaluate the effects of antithrombotic therapy on post-ESD bleeding. METHODS: The published literature was searched on online databases, and all studies were included up to January 2017. Standard forms were used to extract data by 2 independent reviewers. The Newcastle-Ottawa Scale score was used to assess the quality of studies. The pooled odds ratio (OR) was computed for the effect of antithrombotic agents. Publication bias was assessed by funnel plots. Heterogeneity was assessed by the Cochran Q test and I2 statistic. RESULTS: Sixteen retrospective articles were included. Regardless of discontinuation (OR, 1.66; 95% confidence interval [CI], 1.15-2.39; P = .007) or continuation (OR, 8.39; 95% CI, 4.64-15.17; P < .00001), antithrombotic therapy was significantly associated with post-ESD bleeding, particularly for delayed bleeding (OR, 2.66; 95% CI, 1.42-4.98; P = .002). The bleeding rate was higher in the discontinued multiple antithrombotics group (OR, 5.17; 95% CI, 3.13-8.54; P < .00001) than in the discontinued a single antithrombotic group (OR, 2.23; 95% CI, 1.29-3.85; P = .004) and single antiplatelet group (OR, 2.08; 95% CI, 0.93-4.63; P = .07). In the subgroup analysis, resuming antithrombotics within 1 week (OR, 2.46; 95% CI, 1.54-3.93; P = .0002) and using heparin replacement (OR, 4.20; 95% CI, 1.94-9.09; P= .0003) significantly increased post-ESD bleeding risk. Continued use of low-dose aspirin (OR, 1.22; 95% CI, 0.17-8.61; P = .84) did not significantly increase the bleeding risk. CONCLUSIONS: Antithrombotic therapy is a risk factor for post-ESD bleeding, especially for delayed bleeding. Using multiple antithrombotic drugs, resuming antithrombotics within 1 week, and heparin replacement were significantly associated with post-ESD bleeding; but continuous low-dose aspirin was not. However, much larger prospective studies are required.