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The mechanisms accounting for the functional changes of α- and β-cells over the course of Type 1 Diabetes (T1D) development are largely unknown. Permitted by our established technology of high spatiotemporal resolution imaging of cytosolic Ca2+ ([Ca2+]c) dynamics on fresh pancreas tissue slices, we tracked the [Ca2+]c dynamic changes, as the assessment of function, in islet α- and β-cells of female non-obese diabetic (NOD) mice along the development of spontaneous diabetes. We showed that during the phases of islet inflammation, 8 mM glucose-induced synchronized short [Ca2+]c events in β-cells were diminished, whereas long [Ca2+]c events were gradually more triggerable at sub-stimulatory 4 and 6 mM glucose. In the islet destruction phase, the synchronized short [Ca2+]c events in a subset of β-cells resumed at high glucose condition, while the long [Ca2+]c events were significantly elevated already at sub-stimulatory glucose concentrations. In the α-cells, the glucose sensitivity of the [Ca2+]c events persisted throughout the course of T1D development. At the late islet destruction phase, the α-cell [Ca2+]c events exhibited patterns of synchronicity. Our work has uncovered windows of functional recovery in β-cells and potential α-cells functional synchronization in NOD mice over the course of T1D development.

The mechanisms accounting for the functional changes of α- and β-cells over the course of Type 1 Diabetes (T1D) development are largely unknown. Permitted by our established technology of high spatiotemporal resolution imaging of cytosolic Ca2+ ([Ca2+]c) dynamics on fresh pancreas tissue slices, we tracked the [Ca2+]c dynamic changes, as the assessment of function, in islet α- and β-cells of female non-obese diabetic (NOD) mice along the development of spontaneous diabetes. We showed that during the phases of islet inflammation, 8 mM glucose-induced synchronized short [Ca2+]c events in β-cells were diminished, whereas long [Ca2+]c events were gradually more triggerable at sub-stimulatory 4 and 6 mM glucose. In the islet destruction phase, the synchronized short [Ca2+]c events in a subset of β-cells resumed at high glucose condition, while the long [Ca2+]c events were significantly elevated already at sub-stimulatory glucose concentrations. In the α-cells, the glucose sensitivity of the [Ca2+]c events persisted throughout the course of T1D development. At the late islet destruction phase, the α-cell [Ca2+]c events exhibited patterns of synchronicity. Our work has uncovered windows of functional recovery in β-cells and potential α-cells functional synchronization in NOD mice over the course of T1D development.

A physical assessment of the lateral gate-all-around (GAA) nanosheet transistor (NSFET) at the G40M16 node (gate length = 12 nm projected for 2028) of the newly defined beyond-Moore International Roadmap for Devices and Systems [~5 nm node of the predecessor International Technology Roadmap for Semiconductors (ITRS)], supported by 3-D numerical device simulations and based on a proposed per-footprint scheme, is presented. The traditional evaluation scheme to gauge the performance of the transistor ``per effective channel width'' is shown to be improper due to pervasive bulk inversion. Bulk inversion, along the width of the nanosheet and at its ends, obfuscates the dependence of current on sheet/channel width and undermines the presumed added benefit of short-channel effect (SCE) control in the GAA device. The NSFET provides a flexible sheet width, as opposed to that of the FinFET with discrete fins, but the allowed range of sheet width is limited due to significant parasitic capacitance at a relatively narrow width and degraded SCE control and increased resistance for desired wide width. Furthermore, the nanosheet (NS) device density is undermined at a narrow width, especially for decreasing pitch. The FinFET is shown to be a favorable alternative to the NSFET even at the G40M16 node.

In this paper, we present a copper(I)-catalyzed nitrile-addition/N-arylation ring-closure cascade for the synthesis of 5,11-dihydro-6H-indolo[3,2-c]quinolin-6-ones from 2-(2-bromophenyl)-N-(2-cyanophenyl)acetamides. Using CuBr and t-BuONa in dimethylformamide (DMF) as the optimal reaction conditions, the cascade reaction gave the target products, in high yields, with a good substrate scope. Application of the cascade reaction was demonstrated on the concise total syntheses of alkaloid isocryptolepine. Further optimization of the products from the cascade reaction led to 3-chloro-5,12-bis[2-(dimethylamino)ethyl]-5,12-dihydro-6H-[1,3]dioxolo[4',5':5,6]indolo[3,2-c]quinolin-6-one (2k), which exhibited the characteristic DNA topoisomerase-I inhibitory mechanism of action with potent in vitro anticancer activity. Compound 2k actively inhibited ARC-111- and SN-38-resistant HCT-116 cells and showed in vivo activity in mice bearing human HCT-116 and SJCRH30 xenografts. The interaction of 2k with the Top-DNA cleavable complex was revealed by docking simulations to guide the future optimization of 5,11-dihydro-6H-indolo[3,2-c]quinolin-6-ones as topoisomerase-I inhibitors.

BackgroundStudies specifically examining the association between glycated hemoglobin A1c (HbA1c) levels and ischemic stroke/systemic thromboembolism (IS/SE) risk in atrial fibrillation (AF) patients are limited. Here, we investigated the association between HbA1c levels and the risk of IS/SE, as well as major bleeding, among AF patients with or without oral anticoagulants (OACs). We also compared the effectiveness and safety of warfarin and direct oral anticoagulants (DOACs) in different HbA1c categories.MethodsWe utilized medical data from a multi-center healthcare provider in Taiwan, which included 34,036 AF patients with serum HbA1c data available within 3 months after AF being diagnosed. Patients were divided into seven study groups according to their HbA1c levels: ResultsCompared with the patients with HbA1c level Pinteractions > 0.05).ConclusionFor AF patients, IS/SE risk significantly increased once HbA1c levels exceeded 6.5%, and OACs may attenuate these associations. Compared with warfarin, DOACs were more effective and safer across broad HbA1c categories. Therefore, in addition to prescribing DOACs when indicated, more aggressive glycemic control to achieve an HbA1c level

Recently, drug-resistant bacterial infections, especially ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.), have become a critical health issue worldwide, highlighting the emerging need for novel antibacterial agents. In this study, silver nanoparticles were extracted from silver-containing mesoporous bioactive glass (MBG-Ag) using four different matrixes, including water, phosphate buffer saline (PBS), tryptic soy broth (TSB), and taurine (Tau). The inductively coupled plasma-mass spectrometer (ICP-MS) results demonstrated that the silver concentration of Tau-Ag was the highest among the four matrixes. The Tau-Ag was also observed to have 87.35% silver ions in its X-ray photoelectron spectrometer (XPS) spectra. The micrograph of transmission electron microscope (TEM) displayed a uniform distribution of silver nanoparticles, which was confined in a smaller size compared to that in TSB-Ag. Moreover, the peak shifts observed in the Fourier-transform infrared spectrometer (FTIR) spectrum implied that the -SO32− and -NH groups in taurine may interact with silver. A low cytotoxicity was noted for Tau-Ag, with approximately 70% of cells surviving at 0.63 mg/mL. Compared to the other three matrix-induced silver agents, Tau-Ag represented a better antibacterial effect against methicillin-resistant Staphylococcus aureus, with a minimum inhibitory concentration (MIC) value of 0.63 mg/mL and a postponed growth of 0.31 mg/mL observed. Further antibacterial examinations illustrated the presence of remarkable antibacterial activities against vancomycin-resistant Enterococcus feacium, carbapenem-resistant Klebsiella pneumoniae, carbapenem-resistant Acinetobacter baumannii, and carbapenem-resistant Pseudomonas aeruginosa. Given our observations and multiple bioactive functions of taurine (prevent patients from inflammation and oxidative-stress injuries), we anticipate that taurine matrix-induced silver ions would be a biomedical material with a high potential for combatting drug-resistant ESKAPE pathogens.

Background: Reducing hospital readmissions for stroke remains a significant challenge to improve outcomes and decrease healthcare costs. Methods: We analyzed 10,034 adult patients with ischemic stroke, presented within 24 hours of onset from a hospital-based stroke registry. The risk factors for early return to hospital after discharge were analyzed using multivariate logistic regression and classification and regression tree (CART) analyses. Results: Among the study population, 277 (2.8%) had 3-day Emergency Department (ED) reattendance, 534 (5.3%) had 14-day readmission, and 932 (9.3%) had 30-day readmission. Multivariate logistic regression revealed that age, nasogastric tube feeding, indwelling urinary catheter, healthcare utilization behaviour, and stroke severity were major and common risk factors for an early return to the hospital after discharge. CART analysis identified nasogastric tube feeding and length of stay for 72-hour ED reattendance, Barthel Index (BI) score, total length of stay in the Year Preceding the index admission (YLOS), indwelling urinary catheter, and age for 14-day readmission, and nasogastric tube feeding, BI score, YLOS, and number of inpatient visits in the year preceding the index admission for 30-day readmission as important factors to classify the patients into subgroups. Conclusions: Although CART analysis did not improve the prediction of an early return to the hospital after stroke compared with logistic regression models, decision rules generated by CART can easily be interpreted and applied in clinical practice.

Leptomeningeal carcinomatosis (LC) is an uncommon presentation of acute lymphoblastic leukemia (ALL), and it is a devastating and life-threatening complication. The disease affects all levels of the central nervous system, and most patients present with different multifocal neurological symptoms. This case was a 34-year-old male who had acute bilateral blindness secondary to recurrent ALL with meningeal infiltration. Diagnosis of LC is made based on the clinical symptoms and the test results including cranial and spinal magnetic resonance imaging and cerebrospinal fluid (CSF) survey. The differential diagnosis of meningeal enhancement and early treatment are also important for prognosis. This case had a good visual recovery after treatment.

Background: Generally, a person with dementia may be unable to make decisions by themselves and professionals may decide what is best for them. Unfortunately, in most cases, professionals assist a person with dementia to make decisions without clear explanation or consent. Whether a person with dementia possesses dignity in routine care is an important issue. Research objectives: The purpose of this study was to explore the lived experience of the healthcare professionals in providing dignified dementia care in Taiwan. Research design: A qualitative, hermeneutic-phenomenological approach was conducted. Participants: Participants were enrolled by purpose sampling. Researchers performed in-depth interviews to reveal the essential ingredient of dignity within dementia care in Taiwan. A total of 20 cases were enrolled to achieve data saturation. Ethical considerations: This study was approved by the institutional review board. Before conducting the interview, interviewees provided informed consent. Findings: There were three themes and six categories that were addressed and constructed; within the themes, 23 Guidelines for Taiwan Dignified Dementia Care and 12 Principles for Dignified Dementia Care in Taiwan were developed. Discussion: From the data relating to dignity in dementia care, we can develop a more independent and dignified care environment to improve the quality of life of person with dementia in Taiwan. Conclusion: The results indicated that dignity within dementia care was constructed by the lived experience of the healthcare professionals, as well as affected by the culture of the organizations and society at the same time.

Williams syndrome (WS) and 7q11.23 duplication syndrome (Dup7q11.23) are neurodevelopmental disorders caused by the deletion and duplication, respectively, of ~ 25 protein-coding genes on chromosome 7q11.23. The general transcription factor 2I (GTF2I, protein TFII-I) is one of these proteins and has been implicated in the neurodevelopmental phenotypes of WS and Dup7q11.23. Here, we investigated the effect of copy number alterations in Gtf2i on neuronal maturation and intracellular calcium entry mechanisms known to be associated with this process. Mice with a single copy of Gtf2i (Gtf2i+/Del) had increased axonal outgrowth and increased TRPC3-mediated calcium entry upon carbachol stimulation. In contrast, mice with 3 copies of Gtf2i (Gtf2i+/Dup) had decreases in axon outgrowth and in TRPC3-mediated calcium entry. The underlying mechanism was that TFII-I did not affect TRPC3 protein expression, while it regulated TRPC3 membrane translocation. Together, our results provide novel functional insight into the cellular mechanisms that underlie neuronal maturation in the context of the 7q11.23 disorders. Electronic supplementary material The online version of this article (10.1007/s12035-018-1290-7) contains supplementary material, which is available to authorized users.

Cholinergic innervation in the pancreas controls both the release of digestive enzymes to support the intestinal digestion and absorption, as well as insulin release to promote nutrient use in the cells of the body. The effects of muscarinic receptor stimulation are described in detail for endocrine beta cells and exocrine acinar cells separately. Here we describe morphological and functional criteria to separate these two cell types in situ in tissue slices and simultaneously measure their response to ACh stimulation on cytosolic Ca2+ oscillations [Ca2+]c in stimulatory glucose conditions. Our results show that both cell types respond to glucose directly in the concentration range compatible with the glucose transporters they express. The physiological ACh concentration increases the frequency of glucose stimulated [Ca2+]c oscillations in both cell types and synchronizes [Ca2+]c oscillations in acinar cells. The supraphysiological ACh concentration further increases the oscillation frequency on the level of individual beta cells, inhibits the synchronization between these cells, and abolishes oscillatory activity in acinar cells. We discuss possible mechanisms leading to the observed phenomena.

This study collected literature on augmented reality (AR) from academic and patent databases to plot the historic development trajectory of AR and forecast its future research and development trends. A total of 3193 and 13,629 papers were collected from academic and patent databases, respectively. First, a network was established using references from the academic literature; main path analysis was conducted on this reference network to plot the overall development trajectory. Subsequent cluster and word cloud analyses revealed the following five major groups of AR research topics: AR surgical navigation applications, AR education applications, AR applications in manufacturing, AR applications in architecture, and AR applications in visual tracking. Subsequently, the relationships between the overall development trajectory and the five AR research topics were compared. Next, the title and abstract of AR-related academic and patent papers were subjected to text mining to identify keywords with a high frequency of occurrence. The results can provide a reference for industry, government, and academia when planning future development strategies for the AR field. This research adopted an integrated analysis procedure to plot the trajectory of AR technology development and applications successfully and effectively, predict future patent research and development directions and produce technological forecasts.

In this paper, we present a copper(I)-catalyzed nitrile-addition/

The echocardiographic parameter E/e' has been associated with cardiovascular (CV) events. However, few studies have analyzed multiple associated CV outcomes using E/e' in a diverse population of both inpatients and outpatients with and without cardiac diseases and risk factors.Medical records of 75,393 patients without atrial fibrillation (AF) with first available E/e' were retrieved from our hospital database. Patients with mitral valve disease were excluded and the remainder were studied in Protocol 1 (70,819 patients). Patients with hypertension, diabetes mellitus, hyperlipidemia, CV diseases, prior CV events, CV surgeries, and left ventricular ejection fraction (LVEF)50% or missing LVEF were further excluded and the remaining patients were studied in Protocol 2 (14,665 patients). The study outcomes are major adverse cardiovascular events (MACE), which included myocardial infarction (MI), atrial fibrillation (AF), ischemic and hemorrhagic stroke (IHS), hospitalization for heart failure (HHF) and cardiac death. The primary outcome were MACE and each of the MACE components.At the end of maximal 5-year follow-up (median 22.18 months with interquartile range [IQR] 7.20-49.08 months for MACE in Protocol 1, and 23.46 months with IQR 8.15-49.02 months for MACE in Protocol 2), compared with an E/e' value of8, an intermediate value of E/e' 8-15 and a high value of E/e'15 were significantly associated with MACE, MI, AF, IHS, HHF, and cardiac death in Protocol 1 (all p.0001). In Protocol 2, an intermediate E/e' value of 8-15 and a high value of E/e' value15 were significantly associated with MACE, MI, AF, IHS, HHF, and CV death (all p.05), except an intermediate value E/e' 8-15 was not associated with AF.In a diverse population of inpatients and outpatients with and without cardiac diseases and risk factors, the echocardiographic parameter E/e' was associated with cardiovascular events and a useful a marker of risk.

BACKGROUND: Off-label dosing non-vitamin K antagonist oral anticoagulants (NOACs) are commonly prescribed for Asian patients with atrial fibrillation (AF).OBJECTIVE: The purpose of this study was to investigate the associations between inappropriate dosing of NOACs and clinical outcomes.METHODS: We used medical data from a multicenter health care system in Taiwan, which included 2068, 5135, 2589, 1483, and 2342 AF patients taking dabigatran, rivaroxaban, apixaban, edoxaban, and warfarin, respectively. The risks of ischemic stroke/systemic embolism (IS/SE) and major bleeding in patients treated with underdosing or overdosing NOACs were compared to those of on-label dosing NOACs and warfarin.RESULTS: About 27% and 5% of AF patients were treated with underdosing and overdosing NOACs, respectively. Compared to on-label dosing, underdosing NOACs were associated with a significantly higher risk of IS/SE (adjusted hazard ratio [aHR] 1.59; 95% confidence interval [CI] 1.25-2.02; P CONCLUSION: About 3 in 10 Asian AF patients were treated with off-label dosing NOACs in daily practice. Compared to on-label dosing, underdosing was associated with a higher risk of IS/SE, whereas overdosing was associated with a higher risk of major bleeding. Thus, even for Asian AF patients at higher risk for bleeding, NOACs still should be prescribed at the dosing based on clinical trial criteria and guideline recommendations.

This paper describes a simple platform that employs coumarin dye-encapsulated semiconducting polymer dots as a fluorescent probe for ratiometric and sensitive fluoride anion detection, in which the sensing mechanism is based on the deprotection of the tert-butyldimethylsilyl group on coumarin to induce Forster resonance energy transfer.

Direct oral anticoagulants (DOACs) are increasingly prescribed for stroke prevention in atrial fibrillation (AF) ([1][1]). Randomized trials adopted the Cockcroft-Gault (CG) formula to calculate the estimated glomerular filtration rate (eGFR) for appropriate DOAC dosage adjustments, whereas the

Speed and power performances of Si-based stacked-nanowire gate-all-around (GAA) FETs and pragmatic ultra-thin-fin FETs at the 5nm CMOS technology node are projected, compared, and physically explained based on 3-D numerical simulations. The respective device domains are also used to compare integration densities based on 6T-SRAM layouts. Predicted comparable performances and densities, with considerations of the complexity/cost of GAAFET processing versus that of the FinFET with pragmatic simplifications, suggest that the FinFET is the better choice for the future.

A genuine understanding of human exocrine pancreas biology and pathobiology has been hampered by a lack of suitable preparations and reliance on rodent models employing dispersed acini preparations. We have developed an organotypic slice preparation of the normal portions of human pancreas obtained from cancer resections. The preparation was assessed for physiologic and pathologic responses to the cholinergic agonist carbachol (Cch) and cholecystokinin (CCK-8), including 1) amylase secretion, 2) exocytosis, 3) intracellular Ca2+ responses, 4) cytoplasmic autophagic vacuole formation, and 5) protease activation. Cch and CCK-8 both dose-dependently stimulated secretory responses from human pancreas slices similar to those previously observed in dispersed rodent acini. Confocal microscopy imaging showed that these responses were accounted for by efficient apical exocytosis at physiologic doses of both agonists and by apical blockade and redirection of exocytosis to the basolateral plasma membrane at supramaximal doses. The secretory responses and exocytotic events evoked by CCK-8 were mediated by CCK-A and not CCK-B receptors. Physiologic agonist doses evoked oscillatory Ca2+ increases across the acini. Supraphysiologic doses induced formation of cytoplasmic autophagic vacuoles and activation of proteases (trypsin, chymotrypsin). Maximal atropine pretreatment that completely blocked all the Cch-evoked responses did not affect any of the CCK-8-evoked responses, indicating that rather than acting on the nerves within the pancreas slice, CCK cellular actions directly affected human acinar cells. Human pancreas slices represent excellent preparations to examine pancreatic cell biology and pathobiology and could help screen for potential treatments for human pancreatitis.

The relevance of risk preference and forecasting accuracy for investor survival has recently been the focus of a series of theoretical and simulation studies. At one extreme, it has been proven that risk preference can be entirely irrelevant (Sandroni in Econometrica 68:1303–1341, 2000; Blume and Easley in Econometrica 74(4):929–966, 2006). However, the agent-based computational approach indicates that risk preference matters and can be more relevant for survivability than forecasting accuracy (Chen and Huang in Advances in natural computation, Springer, Berlin, 2005; J Econ Behav Organ 67(3):702–717, 2008; Huang in J Econ Interact Coord, 2015). Chen and Huang (Inf Sci 177(5):1222–1229, 2007, 2008) further explained that it is the saving behavior of traders that determines their survivability. However, institutional investors do not have to consider saving decisions that are the most influential investors in modern financial markets. Additionally, traders in the above series of theoretical and simulation studies have learned to forecast the stochastic process that determines which asset will pay dividends, not the market prices and dividends. To relate the research on survivability to issues with respect to the efficient markets hypothesis, it is better to endow agents with the ability to forecast market prices and dividends. With the Santa Fe Artificial Stock Market, where traders do not have to consider saving decisions and can learn to forecast both asset prices and dividends, we revisit the issue of survivability and market efficiency. We find that the main finding of Chen and Huang (2008) that risk preference is much more relevant for survivability than forecasting accuracy still holds for a wide range of market conditions but can fail when the baseline dividend becomes very small. Moreover, the advantage of traders who are less averse to risk is revealed in the market where saving decisions are not taken into account. Finally, Huang’s (2015) argument regarding the degree of market inefficiency is confirmed.

Learning how to forecast is always important for traders, and divergent learning frequencies prevail among traders. The influence of the evolutionary frequency on learning performance has occasioned many studies of agent-based computational finance (e.g., Lettau in J Econ Dyn Control 21:1117–1147, 1997. doi: 10.1016/S0165-1889(97)00046-8 ; Szpiro in Complexity 2(4):31–39, 1997. doi: 10.1002/(SICI)1099-0526(199703/04)2:4 3.0.CO;2-3 ; Cacho and Simmons in Aust J Agric Resour Econ 43(3):305–322, 1999. doi: 10.1111/1467-8489.00081 ). Although these studies all suggest that evolving less frequently and, hence, experiencing more realizations help learning, this implication may result from their common stationary assumption. Therefore, we first attempt to approach this issue in a ‘dynamically’ evolving market in which agents learn to forecast endogenously generated asset prices. Moreover, in these studies’ market settings, evolving less frequently also meant having a longer time horizon. However, it is not true in many market settings that are even closer to the real financial markets. The clarification that the evolutionary frequency and the time horizon are two separate notions leaves the effect of the evolutionary frequency on learning even more elusive and worthy of exploration independently. We find that the influence of a trader’s evolutionary frequency on his forecasting accuracy depends on all market participants and the resulting price dynamics. In addition, prior studies also commonly assume that traders have identical preferences, which is too strong an assumption to apply to a real market. Considering the heterogeneity of preferences, we find that converging to the rational expectations equilibrium is hardly possible, and we even suggest that agents in a slow-learning market learn frequently. We also apply a series of econometric tests to explain the simulation results.

This paper develops a utility-based heterogeneous agent model for empirically investigating intraday traders’ behaviors. Two types of agents, which consist of fundamental traders and technical analysts, are considered in the proposed model. They differ in the expectation of future asset returns and the perceived risk. This paper incorporates the unique characteristics of high-frequency data into the model for the purpose of having a reliable and accurate empirical result. In particular, a two-test procedure is developed to test the market fractions hypothesis that distinguishes the heterogeneous agent model from the representative agent model. The proposed heterogeneous agent model is estimated on the Taiwan Stock Exchange data. The results suggest that fundamental traders expect the correction of over- or under-pricing in the future. Technical analysts act as contrarian traders. Technical analysts also believe that buyer-initiated (seller-initiated) trading will further raise (lower) future prices. The bid-ask spread has a crucial effect on the investment risk for the technical analysts. Moreover, technical analysts are short-sighted, have less market fraction, but perform slightly better.

This paper proposes vertically stacked gate-all-around MOSFET structure with optimized inner spacers to provide superior gate controllability and reduce additional parasitic capacitance simultaneously. To achieve better performance, we evaluate different inner spacer lengths while tuning source/drain doping profile to keep off-state leakage current unchanged. Considering the fabrication uniformity, the key of the conceptual process flow is to etch inner spacers selectively from top to bottom channel. The proposed approach can be applied to low power and ultra-low power design for SoC application without additional mask cost.

Epstein-Barr virus (EBV), an oncogenic human virus, is associated with several lymphoproliferative disorders, including Burkitt lymphoma, Hodgkin disease, diffuse large B-cell lymphoma (DLBCL), and posttransplant lymphoproliferative disorder (PTLD). In vitro, EBV transforms primary B cells into lymphoblastoid cell lines (LCLs). Recently, several studies have shown that receptor tyrosine kinases (RTKs) play important roles in EBV-associated neoplasia. However, details of the involvement of RTKs in EBV-regulated B-cell neoplasia and malignancies remain largely unclear. Here, we found that erythropoietin-producing hepatocellular receptor A4 (EphA4), which belongs to the largest RTK Eph family, was downregulated in primary B cells post-EBV infection at the transcriptional and translational levels. Overexpression and knockdown experiments confirmed that EBV-encoded latent membrane protein 1 (LMP1) was responsible for this EphA4 suppression. Mechanistically, LMP1 triggered the extracellular signal-regulated kinase (ERK) pathway and promoted Sp1 to suppress EphA4 promoter activity. Functionally, overexpression of EphA4 prevented LCLs from proliferation. Pathologically, the expression of EphA4 was detected in EBV(-) tonsils but not in EBV(+) PTLD. In addition, an inverse correlation of EphA4 expression and EBV presence was verified by immunochemical staining of EBV(+) and EBV(-) DLBCL, suggesting EBV infection was associated with reduced EphA4 expression. Analysis of a public data set showed that lower EphA4 expression was correlated with a poor survival rate of DLBCL patients. Our findings provide a novel mechanism by which EphA4 can be regulated by an oncogenic LMP1 protein and explore its possible function in B cells. The results provide new insights into the role of EphA4 in EBV(+) PTLD and DLBCL.