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Tolerance is defined to be a hyporesponsive state following repeated stimulations with bacteria or their virulence factors and has potential impacts on the development of periodontitis. Recently, macrophages have been reported to release chromatin and antimicrobial peptides to form extracellular traps upon bacterial or chemical stimulations. Thus, we explored the roles and mechanisms of tolerance induced by Porphyromonas gingivalis (P. gingivalis) in macrophage extracellular traps (METs). Tolerance in peritoneal macrophages from mice was triggered by repeated P. gingivalis stimulation. METs were observed using fluorescence microscopy, and the levels of extracellular DNA were determined by microplate reader assays. The expression of p-RAF, p-MEK, and p-ERK was examined by Western blot, and reactive oxygen species (ROS) production was explored using flow cytometry. Moreover, the levels of intracellular Ca2+ were also determined by confocal microscopy to identify the possible mechanisms related to the changes in METs in P. gingivalis–pretreated macrophages. Repeated P. gingivalis stimulation contributed to the formation of METs and increased levels of extracellular DNA (p < 0.05). ROS generation and RAF/MEK/ERK phosphorylation were decreased in P. gingivalis–pretreated macrophages compared with non-pretreated cells (p < 0.05), which was inconsistent with the changes in METs. However, in P. gingivalis–pretreated macrophages, the levels of intracellular Ca2+ were significantly increased compared with the single stimulation group. Additionally, inhibition of intracellular Ca2+ resulted in a decrease in the levels of extracellular DNA in P. gingivalis–pretreated cells (p < 0.05). Taken together, P. gingivalis–pretreated macrophages released more METs, possibly related to the increased levels of intracellular Ca2+. [ABSTRACT FROM AUTHOR]

Visible-infrared person re-identification has attracted extensive attention from the community due to its potential great application prospects in video surveillance. There are huge modality discrepancies between visible and infrared images caused by different imaging mechanisms. Existing studies alleviate modality discrepancies by aligning modality distribution or extracting modality-shared features on the original image. However, they ignore a key solution, i.e., converting visible images to gray images directly, which is efficient and effective to reduce modality discrepancies. In this paper, we transform the cross-modality person re-identification task from visible-infrared images to gray-infrared images, which is named as the minimal modality discrepancy. In addition, we propose a pyramid feature integration network (PFINet) which mines the discriminative refined features of pedestrian images and fuses high-level and semantically strong features to build a robust pedestrian representation. Specifically, PFINet first performs the feature extraction from concrete to abstract and the top-down semantic transfer to obtain multi-scale feature maps. Second, the multi-scale feature maps are inputted to the discriminative-region response module to emphasize the identity-discriminative regions by the spatial attention mechanism. Finally, the pedestrian representation is obtained by the feature integration. Extensive experiments demonstrate the effectiveness of PFINet which achieves the rank-1 accuracy of 81.95% and mAP of 74.49% on the multi-all evaluation mode of the SYSU-MM01 dataset. [ABSTRACT FROM AUTHOR]

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Based on the finite-difference time domain (FDTD) method, this paper has studied the absorption characteristics of the all-dielectric absorbers composed of silicon thin film with a multilayer dielectric stack. Broadband absorption was achieved in this paper. For instance, one-dimensional planar structure composed of 60nmSiO2–30nmMgF2–60nmGaN–3000nmSi maintains a broadband absorption ≥ 95% over a wavelength range from 440 to 770 nm. And the whole absorptance maintains 90% in the above spectral band, at an oblique incidence angle of 0.25π, while compared to the absorption property of pure silicon film in the same thickness but less than 70%, the new structure shows the greatly improving. [ABSTRACT FROM AUTHOR]

The aim of this study is to explore the feasibility of using a non-sedation protocol for the evaluation of neonatal congenital heart disease by using 16-cm wide-detector CT with a low radiation dose. Thirty-four neonates (group 1) were enrolled to undergo cardiac CT without sedation between August 2018 and March 2019. The control group (group 2) comprising 20 inpatient neonates was sedated. Cardiac CT was performed using 16-cm area detector 320-row CT with free breathing and prospective ECG-triggering scan mode. The examination completion time, radiation dose, and image quality were compared between the groups. The results of cardiac CT for patients in group 1 who underwent surgery were compared with surgical findings. Intergroup differences in body weight, age, examination completion time, radiation dose, and image quality evaluation were not significant. There was no significant difference in oxygen saturation before and after the examination in group 1. In all, 98 separate cardiovascular abnormalities in 27 group 1 patients were confirmed using surgical reports. The overall sensitivity, specificity, positive predictive value, and negative predictive value of cardiac CT were 94.90%, 100.0%, 100.0%, and 98.53%. The non-sedation protocol can be applied in neonates with congenital heart disease by using 16-cm wide-detector CT with a low radiation dose. Based on the image quality obtained, non-sedative examination did not extend the examination completion time and helped avoid the possible side effects of sedative drugs. [ABSTRACT FROM AUTHOR]

This study sought to investigate the prognostic potential of layer-specific global longitudinal strain (GLS) in predicting cardiac events among non-ST-segment elevated acute coronary syndrome (NSTE-ACS) patients with preserved LVEF. In this prospective study, we enrolled 160 consecutive NSTE-ACS patients with preserved LVEF (≥ 50%) who underwent successful percutaneous coronary intervention (PCI). Transthoracic two-dimensional echocardiography examinations were performed within 48 h of admission (before PCI). Cardiac events were defined as all-cause death, re-infarction, and hospitalization for heart failure. During a median follow-up of 30.2 months, 23 patients (14.4%) developed cardiac events. GLS for all three myocardial layers were reduced in patients with adverse outcome (all P < 0.001). Yet GLSendo (area under curves = 0.85) and GLSmid (area under curves = 0.83) showed relatively higher predictive power than GLSepi when identifying patients with cardiac events. The best cut-off value of GLSendo was − 20.8%, with a diagnostic sensitivity and specificity of 87% and 71% respectively. A significant increase in the risk of cardiac events development was shown among patients with impaired layer GLS (log-rank test, P < 0.001). In conclusion, NSTE-ACS patients with preserved LVEF, layer GLS assessed before PCI all had good abilities to predict cardiac events, which might provide more prognostic information against conventional echocardiographic risk factors. [ABSTRACT FROM AUTHOR]

Periodontitis is a dental plaque–induced chronic inflammatory disease. Long-term exposure of the host to periodontal pathogens leads to a hyporesponsive state to the following stimulations, which is described as endotoxin tolerance. Neutrophils are the most abundant innate immune cells in the body. To clarify the roles of endotoxin tolerance in periodontitis, inflammatory responses in Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS)–tolerized neutrophils were explored in this study. Here, apoptosis and respiratory burst in neutrophils upon single or repeated P. gingivalis LPS stimulations were explored by flow cytometry. Cytokine production (TNF-α, IL-8, and IL-10) in tolerized neutrophils or neutrophils co-cultured with peripheral blood mononuclear cells was determined by ELISA. Phagocytosis of P. gingivalis by tolerized neutrophils was also assayed by flow cytometry. In addition, quality and quantitation of neutrophil extracellular trap (NET) formation were detected using immunofluorescence microscope and microplate reader, respectively. The protein expressions of extracellular signal–regulated kinase1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK) were examined to identify possible mechanisms for the abovementioned changes. Tolerance induced by P. gingivalis LPS significantly suppressed apoptosis, reactive oxygen species (ROS) generation, and phagocytosis in neutrophils (p < 0.05). In both neutrophils alone and co-culture system, repeated P. gingivalis LPS stimulations significantly decreased TNF-α production, but increased IL-10 secretion (p < 0.05). Moreover, in tolerized neutrophils, NET formations were strengthened and there were more released extracellular DNA (p < 0.05). In P. gingivalis LPS-tolerized neutrophils, phosphorylation of ERK1/2 was suppressed compared with that in non-tolerized cells. Taken together, immune responses in neutrophils were reprogrammed by P. gingivalis LPS-induced tolerance, which might be related with the development of inflammation in periodontal tissues. Moreover, ERK1/2 might play important roles in endotoxin tolerance triggered by P. gingivalis LPS. [ABSTRACT FROM AUTHOR]

In this paper, the transmission characteristics of two-dimensional photonic crystal with Hg-1223 cylindrical array in transverse magnetic mode are studied in terahertz-waves by shift operator finite-difference time-domain method. The effects of external temperature and pressure and the period and radius of the dielectric cylinders on the transmission properties of superconducting photonic crystal in terahertz-waves are studied. The simulation results show that external temperature and pressure can be used to change the plasma frequency of superconductor, thus adjusting band gap width of superconducting photonic crystal. The decreasing of the external temperature or the increasing of the pressure have resulted in the increasing of the band gap width of superconducting photonic crystal, while increasing external temperature or decreasing the pressure can decrease the band gap width, which gradually becomes apparent as temperature increases or pressure decreases. In addition, the increasing of the periods and radius of superconducting cylinders can also broaden the band gap of superconducting photonic crystal in terahertz-waves. The research in this paper is in terahertz-waves, and all the cutoff frequencies of band gap are between 0.1 and 6 THz, which provides references for practical application of superconducting photonic crystal. [ABSTRACT FROM AUTHOR]

In this paper we propose an efficient method for creating macroscopically distinct mechanical superposition states in an ultra strongly-coupled light-matter system. By modulating the opto-mechanical coupling sinusoidally, the radiation pressure can be turned into a built-in resonant driving force effectively. Thus the mechanical displacement can be significantly amplified. [ABSTRACT FROM AUTHOR]

In this paper, a biosensor based on 1D-PhC (one-dimensional photonic crystal) is proposed for detecting colony of E. coli (Escherichia coli) by analyzing the volume fraction of E. coli in analyte. The performance of the biosensor is evaluated by FDTD (finite-difference time-domain) method, and the parameters of the biosensor are optimized by orthogonal experiments. The simulation results show that the optimum parameters of the biosensor are A1B5C5D4E5 with the FOM (figure of merit) and S (sensitivity) of 125 and 174a nm/RIU, respectively. The center wavelength is the major factor affecting the performance of the biosensor. The S and FWHM (full width at half maximum) of the sensor are increased with the increasing of the center wavelength. In addition, the effective refractive index of the analyte at different volume fractions of E. coli is calculated by the Bruggeman model. The volume fraction of E. coli in the analyte is positively correlated with the resonance wavelength shift of the biosensor, and the linear correlation coefficient is 0.996. Therefore, it is feasible to detect the number of E. coli in the analyte by the resonance wavelength shift of the biosensor. [ABSTRACT FROM AUTHOR]

A novel graphene photonic crystal structure is proposed and designed in this paper; each unit period is composed of graphene, metal, and magnesium fluoride. We investigate the optical properties of this structure in the visible to near-infrared range by means of finite-difference time-domain method. We examined the influence of structural parameters (metal material, thickness, period number, etc.) on the optical response of the structure and found that it can be transparent in visible range and can shield most of the near-infrared rays. As a result, the proposed graphene photonic structure enables potential applications in selective near-infrared shielding material. [ABSTRACT FROM AUTHOR]

The electromagnetic property of graphene is studied by finite-difference time-domain (FDTD) method. As the graphene has excellent electrical conductivity and high transparency, it has certain advantages as a transparent electrode for solar cells. This paper designs a three-layer film structure composed of graphene, silicon, and silicon dioxide (SiO2). Then, the effects of the chemical potential and the scattering rate of the graphene on the light absorption of the film are studied. The study found that the electromagnetic property of graphene is relatively stable, which is not easily influenced by the external environment. After changing its chemical potential, scattering rate, and other parameters, it is found that the film absorption rate is less affected unless the large range of chemical potential changes; it will lead to a decline in the absorption rate of light. [ABSTRACT FROM AUTHOR]

By virture of taking into account the two atoms' spatial motion, we evaluate the dynamics of geometric measure of quantum discord(GMQD) and Bell nonlocality of a two-qubit system in an ideal single-mode ring cavity for two types of extended Werner-like(EWL) internal states. It is shown that both Bell nonlocality and GMQD are closely related to the initial entanglement parameter, the initial state's purity and the wave packet's width. We also find that, for the initial state W±´, the sudden disappearance and sudden regeneration of GMQD and Bell nonlocality both happen, while for the initial state W±, the phenomena of sudden disappearance and sudden regeneration of Bell nonlocality still exist, but that of GMQD does not occur, that is, GMQD decays to zero asymptotically as time goes on. What's more, we have proved that the preservation of GMQD is much longer than that of Bell-inequality violation. [ABSTRACT FROM AUTHOR]

A discrete finite-difference time-domain (FDTD) method based on Maxwell’s equations is proposed to solve the scattered-field equation for dispersive media. The equations for the scattered field in a plasma medium are first derived, then used to calculate the radar cross-section (RCS) of three-dimensional targets, viz. a plasma sphere and a rectangular plate. When using such an FDTD method to compute the far-field scattering characteristics of a target, the near- to far-field transformation technique is generally required, which involves artificial setting a connection boundary between the total and scattered field in the computational space in order to calculate the latter and thereby the RCS of the target. This connection boundary must be set separately and appropriate computational grids added. However, by discretizing the Maxwell’s equations describing the scattered field, the resulting field in the computational space is already the scattered field and can be used directly to calculate the far-field properties of the target. In this way, the additional processing for the edge of the scattered field and computational space is avoided. Numerical calculations herein show that this FDTD approach for the scattered field is universal to some extent, being suitable for not only homogeneous but also dispersive media. [ABSTRACT FROM AUTHOR]

In this paper, modified transmission matrix method is used to construct one-dimensional multilayer composite membrane structure doped with graphene defect. The optimal construction can be found to realize reciprocity transmission by comparing the influence of the time inversion-symmetry and space inversion-symmetry doped on nonreciprocal transmission. The simulation results show that it cannot ensure the nonreciprocal transmission with rotatory material only. Nonreciprocal transmission should be designed through the structure damage of the space inversion-symmetry to realize it. The structure absorption peak position will move to the direction of the wavelength increase along with the increase of thickness of rotation media. The structure shows the approximate perfect absorption characteristics. [ABSTRACT FROM AUTHOR]

In this paper, we present a practical system to automatically suggest the most pairing clothing items, given the reference clothing (upper-body or low-body). This has been a challenge, due to clothes having a variety of categories. Clothing is one of the most informative cues for human appearance. In our daily life, people need to wear properly and beautifully to show their confidence, politeness and social status in various occasions. However, it is not easy to decide what to wear and how to coordinate their own clothes. To address this problem, we propose a recommendation approach that includes clothing region detection, clothing pair recommendation and distance fusion. Clothing region detection based on Faster R-CNN is used to detect clothing region. Clothing pair recommendation consists of a quadruple network architecture, where one dual network of the architecture adopts Siamese convolution neural network architecture. Training examples are pairs of upper-body and low-body clothing items that are either compatible or incompatible. The other dual network is used to learn clothing style features of the input image. This framework is designed to learn a feature transformation from the images of clothing items into two latent spaces, which we call them compatible space and style space respectively. After training the two dual networks, we use a distance fusion method to fuse the features extracted from the compatible and style dual networks. To acquire an optimized model and verify our proposed method, we expand an existing large clothing dataset WoG (Weather-to-Garment), and the resulted dataset is called “How to Wear Beautifully” (H2WB). Experiments on the H2WB dataset demonstrate that our approach is effective with clothing region detection and clothing pair recommendation as well as distance fusion. [ABSTRACT FROM AUTHOR]

Correction to: Inflammation https://doi.org/10.1007/s10753-021-01611-y The original published version of this article contained a mistake, and the authors would like to correct it. The correct co-first author annotations are as follows: Yu-jie Liu and Jia-lu Chen have contributed equally to this work and share first authorship. There are errors in co-first author annotations. [Extracted from the article]

We study the decoherence dynamics of quantum tunneling of a two-level atom coupled into a single-mode electromagnetic field. Atomic internal and external degrees are entangled with the cavity field due to recoil during emission of a photon. We show that the quantum tunneling period depends on the distance between the two wells, and the tunneling process itself may or may not decohere depending on the distance between the two wells of the external potential compared to the wavelength corresponding to the internal transition. [ABSTRACT FROM AUTHOR]

We have developed an electrochemical method for the determination of 17β-estradiol. A glassy carbon electrode was modified with a composite made from copper sulfide nanosheets, gold nanoparticles, and glucose oxidase. The copper sulfide nanosheet was prepared by a single-step hydrothermal process, and its properties were characterized by X-ray powder diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy and transmission electron microscopy. Finally, an estradiol-specific aptamer was assembled on the electrode. The copper sulfide nanosheet on the electrode surface acts as a relatively good electrical conductor. Glucose oxidase acts as an indicator, and the dual modification of glucose oxidase and gold nanoparticles for signal amplification. The determination of 17β-estradiol was performed by differential pulse voltammetry of glucose oxidase because the signal measured at typically −0.43 V depends on the concentration of 17β-estradiol because addition of 17β-estradiol at electrode hinders electron transfer. A linear relationship exists between the peak current and the logarithm of concentration of 17β-estradiol in the 0.5 pM to 5 nM range, with a 60 f. detection limit (at 3σ/S). The method displays good selectivity over bisphenol A, 1-aminoanthraquinone and naphthalene even if present in 100-fold concentrations. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

A novel CuS-graphene (CuS-Gr) composite was synthesized to achieve excellent electrochemical properties for application as a DNA electrochemical biosensor. CuS-Gr composite was prepared by a hydrothermal method, in which two-dimensional graphene served as a two-dimensional conductive skeleton to support CuS nanoparticles. A sensitive electrochemical DNA biosensor was fabricated by immobilizing single-stranded DNA (ss-DNA) labeled at the 5′ end using 6-mercapto-1-hexane (HS-ssDNA) on the surface of Au nanoparticles (AuNPs) to form ssDNA-S-AuNPs/CuS-Gr, and hybridization sensing was done in phosphate buffer. Cyclic voltammetry and electrochemical impedance spectroscopy were performed for the characterization of the modified electrodes. Differential pulse voltammetry was applied to monitor the DNA hybridization using an [Fe(CN)] solution as a probe. Under optimum conditions, the biosensor developed exhibited a good linear relationship between the current and the logarithm of the target DNA concentration ranging from 0.001 to 1 nM, with a low detection limit of 0.1 pM (3 σ/ S). The biosensor exhibited high selectivity to differentiate one-base-mismatched DNA and three-base-mismatched DNA. The results indicated that the sensing platform based on CuS-Gr provides a stable and conductive interface for electrochemical detection of DNA hybridization, and could easily be extended to the detection of other nucleic acids. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

To study the association between known risk factors for cardiovascular disease and intima-media thickness (IMT) in the carotid and popliteal arteries in middle-aged and elderly Chinese adults. 686 middle aged and elderly Chinese adults from the China Da Qing Diabetes Prevention Study who had full clinical, laboratory, ultrasound examination results were enrolled in the study. Common carotid artery (CCA) and popliteal artery (PA) IMT were obtained using high resolution ultrasound machine. Pearson's or Spearman's correlation analysis and logistic regression analysis were used to determine association between risk factors [age, gender, tobacco smoking, body mass index (BMI), diabetes mellitus (DM), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol, total triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, glycosylated hemoglobin (HbA)] and CCA- or PA-IMT. The age range of the study population was 45-87 years, 384 of them (56 %) were women. The prevalence of high blood pressure and DM was 60.6 and 68.8 %, respectively. Participants in DM group tended to be older, had greater value for SBP, HbA and PA-IMT, but smaller value for DBP than those in control group. Smoke status, BMI, blood lipids and CCA-IMT were not statistically different between groups. Pearson's or Spearman's rank correlation analysis showed that CCA-IMT had a positive correlation with age, gender, DM, SBP, BMI and HbA, negative correlation with HDL-C. PA-IMT showed a positive correlation with age, gender and SBP. Univariate logistic regression analysis showed that elevation of age, SBP, BMI, HbA and having DM were significant predictors of CCA-IMT thickening, so was reduction of HDL-C. Risk factors that predicted significant thickening of PA-IMT were age, gender, tobacco smoking. After adjusted for age and gender, except HDL-C, the other four risk factors (SBP, BMI, HbA and having DM) that predicted CCA-IMT thickening remained significant; however none of the risk factors predicted PA-IMT thickening after adjusted for age and gender. The current results provide evidence that CCA-IMT is a superior marker for atherosclerosis compared with PA-IMT. Aggressive control of SBP, HbA and proper control of weight may postpone thickening of CCA-IMT. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to compare the radiofrequency (RF) injury effect on cartilage in the different settings that are mostly used in clinical work under rigidly controlled laboratory conditions. Methods: Twelve fresh porcine knees were used in our study. Five treatment areas were created on the femoral condyles of each knee: the control group, coagulation (setting 2) group, coagulation (setting 7) group, ablation (setting 2) group, and ablation (setting 7) group. Hematoxylin/eosin staining, dual fluorescence staining, and the GAG content were observed to evaluate the histological cartilage changes, vacuolar cell rate of chondrocytes, depth of chondrocyte death, and detection of GAG content. Results: Vacuolar cell rates of chondrocytes in each experimental group were higher than that in the control group ( P < 0.05); there was no significant difference in vacuolar cell rate among experimental groups. Dual fluorescent staining showed that the ablation (setting 7) group had a smaller depth of cell death than did the coagulation (setting 2) group ( P < 0.05); the other experimental groups showed no statistically significant difference (n.s.). In addition, there was no significant difference in GAG content between the experimental groups and control group (n.s.). Conclusions: The coagulation mode results in heavier thermal radiation injury to chondrocytes than does the ablation mode. Higher-power settings in the ablation mode result in lower thermal radiation injury and may be most suitable for cartilage debridement. [ABSTRACT FROM AUTHOR]

The uniaxial ratcheting behavior of a polyetherimide (PEI) polymer 'TECAPEI' was studied using stress-controlled cyclic loading at room temperature, including both cyclic tension-compression with non-zero tensile mean stress and tension-unloading tests. The experimental observations were focused on the time-dependent ratcheting of the PEI polymer revealed in cyclic tests at diverse stress rates and with different peak stress holding times. The results showed that the PEI polymer shows obvious ratcheting deformation; i.e., the ratcheting strain accumulates progressively in the tensile direction during stress-controlled cyclic tests with non-zero mean stress. The ratcheting is highly dependent on the applied mean stress and stress amplitude, and is also characterized by a strong time-dependency during the cyclic stressing at diverse stress rates and with different peak stress holding times. The time-dependent ratcheting of the PEI polymer is caused mainly by its remarkable viscosity. A comparison of the ratcheting occurring before and beyond the ultimate stress point of the PEI polymer showed that the ratcheting beyond the ultimate stress point is more significant than that occurring before that point. [ABSTRACT FROM AUTHOR]

The periodic dielectric slabs are investigated. The reflection and transmission characteristics of electromagnetic wave are researched when photonic crystals are moved at a uniform velocity close to the light speed under the relativistic conditions. When the motion direction of photonic crystal is perpendicular to the propagation direction of electromagnetic wave, the electromagnetic band gap is formed alternately by the reflection spectrum of photonic crystal changed with velocity. The gap is different from the traditional electromagnetic band gap, which is not a function of the spectrum but corresponding to the velocity. The peculiar phenomenon generated by electromagnetic wave at different velocity band is called velocity band gap. The velocity band gap is affected by the frequency of electromagnetic wave, period of photonic crystal, permittivity and other parameters. It varies periodically in the whole velocity range and decreases with the increasing velocity. The velocity band gap is expanded and moved to the low velocity interval with the period of photonic crystal increasing. When the difference in permittivity of the two adjacent dielectric slabs becomes higher and the frequency of electromagnetic wave increases, the velocity band gap is changed accordingly. The change is similar to the state in which a spring fixed at one end is stretched, but the change in velocity band gap is not uniform. [ABSTRACT FROM AUTHOR]

Charred areca nut (CAN) is used to treat dyspepsia and abdominal distension in children. However, reports revealed that arecoline, the most important active constituent of CAN, possesses potential toxicities. This study was designed to investigate the optimum arecoline content in CAN, using the 'target constituent removal combined with bioactivity assay' strategy. Based on PTLC method, we prepared CAN lacking all arecoline (WAC-100R) and a series of different ratios of arecoline-removed CAN samples (WAC-Rx). MTT and acute toxicity assays indicated that decreasing content by 50% decreased CAN toxicity significantly. Animal results revealed arecoline contents over 50% could guarantee the beneficial effects of CAN on gastrointestinal tract. Additionally, decreasing arecoline content in CAN by 50% decreased its pro-apoptotic effects significantly. Furthermore, decreasing 50% arecoline content in CAN down-regulated the expressions of Cleaved-Caspase-3, c-jun, c-fos, COX-2, PGE2, and IL-1α. Thus, our results revealed that CAN with 50% arecoline content (WAC-50R) has similar beneficial effects on the gastrointestinal tract to CAN, whereas its toxicity was decreased significantly. Collectively, our study suggested that the strategy of 'target constituent removal combined with bioactivity assay' is a promising method to identify the optimum arecoline content in CAN, which is approximately 0.12%. [ABSTRACT FROM AUTHOR]