Development and Mechanism Investigation of Novel Thioacetalized Indoles as Antiphytoviral Agents.

Potato virus Y (PVY) is a highly destructive pathogen that infects Solanum tuberosumvL., commonly known as potato, a crop that produces one of the most crucial food staples of the world. The PVY viral infection can considerably reduce the yield and quality of potatoes, thereby causing significant economic ramifications. Given the unsatisfactory performance of commercially available antiviral agents against PVY, we synthesized a series of novel indole-derived compounds followed by their bioevaluation and investigation of the mechanisms governing their anti-PVY activity. These indole-based derivatives contain dithioacetal as a key chemical moiety, and most of them exhibit promising anti-PVY activities. In particular, compound B2 displays remarkable in vivo protective and inactivating properties, with half-maximal effective concentration (EC50) values of 209.3 and 113.0 µg/mL, respectively, in stark contrast to commercial agents such as ningnanmycin (EC50 = 281.4 and 136.3 µg/mL, respectively) and ribavirin (EC50 = 744.8 and 655.4 µg/mL, respectively). The mechanism using which B2 enhances plant immune response to protect plants from PVY is elucidated using enzyme activity tests, real-time quantitative polymerase chain reaction (RT-qPCR), and proteomics techniques. This study aims to pave the way for developing candidate pesticides and related molecules using antiphytoviral activity.

Cardiovascular Health Index Scores and Pregnancy-Induced Hypertension: An Association Study.

Objective: This cohort study investigated the association between cardiovascular health index scores and pregnancy-induced hypertension (PIH). Methods: A total of 1466 first-time pregnant women who delivered a single child between 2006 and 2016 were included in the study. All participants underwent a physical examination before delivery, and seven cardiovascular health indexes were collected and scored. Three groups were created based on the tri-sectional quantiles of the total score to observe whether PIH occurred among the groups. A dichotomous logistic regression analysis was carried out to investigate the relationship between cardiovascular health index scores and the occurrence of PIH. Results: During the observation of 1150 subjects, 103 cases of PIH were identified, resulting in an incidence rate of 8.96%. The study found that the incidence of PIH in the three groups was 17.5% in the first group, 6.7% in the second, and 5.8% in the third group. These rates showed a sequential decrease with statistically significant differences (P < .001). The multifactorial regression analysis revealed that after adjusting for various factors, there was a significant inverse relationship between cardiovascular health index scores and the risk of PIH. Specifically, for every one-point increase in the seven cardiovascular health index scores, the risk of PIH decreased by 29% (OR = 0.71, 95% CI 0.59-0.86). Conclusions: The study found an inverse correlation between cardiovascular health index scores and PIH, with higher scores associated with lower incidences of PIH. Each cardiovascular health indicator helps to lower the risk of PIH, and optimum cardiovascular health behaviors and variables are protective factors against PIH.

New alkaloids and their in vitro antitumor activity of Corydalis balansae.

The chemical investigation on Corydalis balansae resulted in the isolation of three previous undescribed compounds (1, 10, and 11) and 17 known compounds. Compound 1 and 2 were obtained as two lignanamide dimers, and compound 11 had a spiro [benzofuranone-benzazepine] skeleton, which was found in Corydalis for the first time. The structures of new compound were determined by the detailed analysis of 1D/2D NMR, UV, and IR data. Absolute configurations of compounds 10 and 11 were defined by their crystal X-ray diffraction data and calculations of electronic circular dichroism (ECD). The CCK-8 method was used to assay the inhibition effect of all the compounds on the growth of Hela, MGC-803, A549, and HepG2 cancer cells. Compound 2, 13, and 14 showed moderate inhibitory activity against the tested cell lines. Compound 2 exhibited potential antitumor activity against MGC-803 cells with an IC50 value of 20.8 µM, while the positive control etoposide was 17.3 µM. Furthermore, results from the cellular-mechanism investigation indicated that compound 2 could induce S-phase cell-cycle arrest and MGC-803 cells apoptosis, which was triggered by the up-regulation of PARP1, caspase-3 and -9, Bax, and down-regulation of Bcl-2. The 2-induced strong apoptosis indicated that compound 2 had good potential as an antitumor lead compound.

Combined spinal-epidural anesthesia with acupoint injection for labor anesthesia reduces IL-1ß/IL-10 ratio in maternal peripheral blood, umbilical cord blood and improves the labor outcomes: A prospective randomized controlled trial.

BACKGROUND: This study aimed to investigate the effects of combined spinal-epidural anesthesia (CSEA) with acupoint injection (AI) on the maternal-fetal expression of interleukin-1ß (IL-1ß), interleukin-10 (IL-10), analgesia effect, and labor outcomes. METHODS: A total of 360 healthy primiparas were randomized into the CSEA+AI group, the CSEA group, the AI group, and the control group (n = 90, each group) according to the labor analgesia methods. RESULTS: Compared to the CSEA group, the CSEA+AI group had significantly lower visual analog scale (VAS) scores, adverse events, dose of ropivacaine/sufentanil, and shorter labor durations. The IL-1ß/IL-10 ratio in maternal peripheral blood and umbilical cord blood was reduced in the CSEA+AI group compared with the CSEA group. CONCLUSION: The combination of CSEA and AI can reduce the ratio of IL-1ß/ IL-10 in maternal peripheral blood and umbilical cord blood, which can effectively relieve labor pain.

Cyberbullying victimization and nonsuicidal self-injury in adolescents: Testing a moderated mediating model of emotion reactivity and dispositional mindfulness.

BACKGROUND: Little is known about how cyberbullying victimization may influence adolescent nonsuicidal self-injury (NSSI) and what conditions may buffer the detrimental effects of cyberbullying victimization. By integrating multiple theories, this study investigated emotion reactivity as an underlying mediator and mindfulness as a potential moderator to explain the link between cyberbullying victimization and NSSI among Chinese adolescents. METHOD: A total of 2,523 participants with an age range of 11 to 16 years old (Mage = 13.22, SD = 1.60, 48.4% girls) completed assessments. RESULTS: After controlling SES, age, gender, traditional bullying victimization, and child maltreatment, latent moderated structural equation modeling revealed that emotion reactivity mediated the association between cyberbullying victimization and NSSI. In addition, dispositional mindfulness was found to buffer the relation between cyberbullying victimization and NSSI, but not the relation between cyberbullying victimization and emotion reactivity. LIMITATIONS: This study was cross-sectional in nature and relied exclusively upon self-report measures. CONCLUSIONS: The findings provide researchers and practitioners with a deeper understanding of the relation between cyberbullying victimization and NSSI among adolescents and its underlying mechanism. Suggested intervention and prevention strategies include helping youth reduce emotion reactivity to break the cyberbullying victimization to NSSI cycle and to enhance youths' mindfulness to buffer against the ill effects of cyberbullying victimization.

Acupoint Injection Decreases Anesthetic Cosumption during Combined Spinal-Epidural and Patient-Controlled Epidural Labor Analgesia.

OBJECTIVE: To explore if acupoint injection can improve analgesic effects or delivery outcomes in parturients who received combined spinal-epidural analgesia (CSEA) and patient-controlled epidural analgesia (PCEA) for labor analgesia. METHODS: A total of 307 participants were prospectively collected from July 2017 to December 2019. The participants were randomized into the combined acupoint injection with CSEA plus PCEA group (AICP group, n=168) and CSEA plus PCEA group (CP group, n=139) for labor analgesia using a random number table. Both groups received CSEA plus PCEA at cervical dilation 3 cm during labor process, and parturients of the AICP group were implemented acupoint injection for which bilateral acupoint of Zusanli (ST 36) and Sanyinjiao (SP 6) were selected in addition. The primary outcome was Visual Analogue Scale (VAS) score, and the secondary outcomes were obstetric outcomes and requirement of anesthetics doses. Safety evaluations were performed after intervention. RESULTS: The VAS scores were significantly lower in the AICP group than in the CP group at 10, 30, 60, and 120 min after labor analgesia (all P<0.05). The latent phase of the AICP group was shorter than that of the CP group (P<0.05). There were less additional anesthetics consumption, lower incidences of uterine atony, fever, pruritus and urinary retention in the AICP group than those in the CP group (all P<0.05). CONCLUSION: Acupoint injection combined CSEA plus PCEA for labor analgesia can decrease the anesthetic consumption, improve analgesic quality, and reduce adverse reactions in the parturients. (Registration No. ChiMCTR-2000003120).

Flavonol glycosides and phenylpropanoid glycosides with inhibitory effects on microglial nitric oxide production from Neoshirakia japonica.

Five new flavonol glycosides (1-5), one new phenylpropanoid glycoside (6), and nine known glycosides (7-15) were isolated from the stems and leaves of Neoshirakia japonica. The structures of the new compounds were determined by detailed analysis of spectroscopic data (HRESIMS, 1D and 2D NMR) and acid hydrolysis experiment. The antineuroinflammatory effects of all the isolates were evaluated by inhibiting NO production against LPS-induced BV-2 microglial cells. Compounds 1, 8, and 9 showed more potent inhibitory activities with IC50 values of 2.7, 5.5, and 4.1 µM, respectively, than that of the positive control minocycline (IC50 = 15.6 µM), while compounds 7 (IC50 = 17.0 µM) and 10 (IC50 = 24.3 µM) also displayed inhibitory activities to a certain degree.

Simultaneous electrochemical aptasensing of patulin and ochratoxin A in apple juice based on gold nanoparticles decorated black phosphorus nanomaterial.

Simultaneous detection of patulin (PAT) and ochratoxin A (OTA) in food products is in great demand, which can prevent toxins from being exposed to human and animal bodies. However, simultaneous detection of multiple targets still faces a challenge. Herein, we developed a novel electrochemical aptasensor for the simultaneous detection of PAT and OTA in apple juice based on gold nanoparticles decorated black phosphorus (AuNPs-BP) nanomaterial. AuNPs-BP function?/work? as a sensing platform for loading much different electrochemical signal molecules functionalized aptamers. In this context, methylene blue functionalized PAT aptamers (Mb-PAT-aptamers) and ferrocene functionalized OTA aptamers (Fc-OTA-aptamers) have been introduced here to fabricate the aptasensor. Fc close to electrode surface showed a strong signal, whereas Mb was far away from electrode surface so exhibited a weak signal in the absence of OTA and PAT. Two kinds of electrochemical signal changes have been recorded dependent on target of OTA and PAT concentrations. So, simultaneous detection of OTA and PAT is achieved. Under the optimum conditions, using this developed biosensor, PAT and OTA can be quantified at a linearity range of 0.01 × 10-7 µg·mL-1 ~ 0.10 µg·mL-1. In addition, it also has good selectivity, stability and repeatability. For the practical application, it shows promising performance for the simultaneous detection of PAT and OTA in apple juice.

Diterpenoids and triterpenoids from Triadica rotundifolia and their effects on microglial nitric oxide production.

Four new diterpenoids (1-4), three new triterpenoids (12-14), and seven known diterpenoids (5-11) were obtained from an aqueous EtOH extract of the aerial parts of Triadica rotundifolia. The structures of new compounds were determined by spectroscopic techniques. Their absolute configurations were verified via single-crystal X-ray diffraction data, Mo2(OAc)4 induced electronic circular dichroism (ECD), and ECD calculations. The antineuroinflammatory effects of the isolates were assessed by inhibiting NO production in LPS-induced BV-2 microglial cells. Compared with the positive control minocycline (IC50 = 16.1 µM), compounds 3, 8, 11 showed moderate inhibitory activities with IC50 values of 35.9, 17.0, 31.5 µM, respectively.

[Nutrient resorption patterns of Phragmites australis leaves and its response to soil moisture in Yangguan wetland, Dunhuang, Northwest China]. / æ•¦ç Œé˜³å ³æ¹¿åœ°èŠ¦è‹‡å¶ç‰‡å »åˆ†é‡å¸æ”¶æ¨¡å¼åŠå ¶å¯¹åœŸå£¤æ°´åˆ†çš„å“åº”.

Nutrient resorption of leaves is an important nutrient conservation mechanism for plants in nutrient-poor habitats. Understanding the responses of leaf nutrient resorption to soil moisture is helpful to reveal the adaptation strategies of plants to the environment. In this study, the dominant plant in the Yangguang wetland of Dunhuang Phragmites australis was used as research material, to explore nitrogen and phosphorus resorption patterns of P. australis leaves and their responses to soil moisture under different moisture regimes, i.e. high (33.5%±1.9%), medium (26.4%±1.3%) and low (11.3%±1.5%). The results showed that: 1) With the decreases of soil moisture, soil N concentration decreased significantly, and N concentrations in mature and senescent leaves increased significantly, the P concentration in mature and senescent leaves as well as in soil did not change. 2) N resorption efficiency of leaves under high moisture condition was 76.1%, which was significantly higher than the medium (65.5%) and low (62.5%) moisture conditions. P resorption efficiency varied among different moisture conditions. 3) The N concentrations of mature and senescent leaves were negatively correlated with N resorption efficiency. There was no significant correlation between P concentration and P resorption efficiency in mature leaves, but the P concentration of senescent leaves was negatively correlated with P resorption efficiency of leaves. As a result, water scarcity is not conducive to leaf N resorption.

Effect of morphine added to multimodal cocktail on infiltration analgesia in total knee arthroplasty: A meta-analysis of randomized controlled trials.

BACKGROUND: The local injection of multimodal cocktail is currently commonly used in the treatment of postoperative pain after total knee arthroplasty (TKA). It is still inconclusive whether the morphine added to the intraoperative injection mixture could make some difference. This meta-analysis aimed to evaluate the efficacy and safety of additional morphine injection on postoperative analgesia in TKA, and provide some useful information on morphine usage in clinical practice. METHODS: The randomized controlled trials (RCTs) in databases including PubMed, Web of Science, Embase, Cochrane Library, Chinese biomedical literature database (CBM), and Chinese National Knowledge Infrastructure (CNKI) databases were systematically searched. Of 623 records identified, 8 RCTs involving 1093 knees were eligible for data extraction and meta-analysis according to criteria included. RESULTS: Meta-analysis showed that the use of local morphine injection was not associated with significant pain relief within 48 hours postoperatively at rest and on motion (P > .05, all). The use of morphine reduced postoperative total systemic opioids consumption (P < .05). This study found no significant differences in other outcomes including knee flexion range of motion (ROM) (P > .05), extension ROM (P > .05), The Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores (P > .05), Post-operative nausea and vomiting occurrence (P > .05) regardless of the presence of morphine or not in the injections. CONCLUSION: Additional morphine added to multimodal cocktail did not decrease the postoperative pain scores significantly based on our outcomes, but it reduced the systemic postoperative opioids consumption in total knee arthroplasty.

The suitability of rare earth elements for geographical traceability of tea leaves.

BACKGROUND: Rare earth elements (REEs) have been used for the identification of the geographical origins of an increasing number of foods. This study analyzed the effects of geographical origin, harvest season, variety, and their interactions on REEs in tea leaves to investigate whether REEs were suitable for geographical identification of tea leaves. Tea leaves of different varieties and the corresponding soils were collected in different seasons from different areas of China. The concentrations of 14 REEs in tea leaves and soils were determined, and then analyzed with one-way analysis of variance (ANOVA), multi-way ANOVA, correlation analysis, and linear discriminant analysis. RESULTS: All factors significantly affected the contents of REEs in tea leaves. The concentrations of REEs in tea leaves were related to those in provenance soils. However, the concentrations of most REEs in tea leaves were primarily affected by the harvest season. CONCLUSION: Seasonal variations should be considered when REE fingerprinting is applied for the identification of tea for authentication purposes. © 2019 Society of Chemical Industry.

The reduction effects of riparian reforestation on runoff and nutrient export based on AnnAGNPS model in a small typical watershed, China.

The continuous deterioration of the aquatic environment in rivers and streams is increasingly causing social and political tensions. To alleviate aquatic environmental problems, especially for the nonpoint source pollution, establishment of riparian forest buffers has been demonstrated as an effective control measure. However, few comprehensive studies of the reduction effects of riparian reforestation on the aquatic environment have been performed, particularly in identifying the suitable widths of reforestation projects. In this paper, the Annualized Agricultural Non-Point Source (AnnAGNPS) model was used to simulate the reduction effects of riparian reforestation on runoff and nutrient loads in Wucun watershed, China. The results showed that 20-m, 40-m, and 60-m widths of riparian buffer reforestation had significant effects on the yearly loads of total nitrogen (TN) and total phosphorus (TP), with reduced rates of 23.21 to 56.2% and 18.16 to 52.14%, respectively. The reduction effect on annual runoff varied from 2.8 to 5.4%. Furthermore, the reduction effect of nutrients performed best during the transition period, while the best runoff reduction was found during the dry period. These distinct reductions indicated that the implementation of riparian forest buffers was capable of reducing the risk and frequency of flooding and eutrophication, especially during the wet and transition periods. Additionally, the 20-m width of riparian buffer reforestation achieved the highest reduction efficiency for runoff, and the 40-m width was the most suitable reforested riparian buffer width for TN and TP. Therefore, 40 m may be the optimum buffer width for the implementation of riparian reforestation in the Wucun watershed. These research results provided scientific information on selecting the optimum buffer width for aquatic environmental regulators and managers as the reduction effects of different widths of riparian buffers on runoff and nutrients were different when considering buffer reforestation.

Analysis of Triacylglycerols in Castor Oil Through Liquid Chromatography-Mass Spectrometry Based on Fourier Transform-Ion Cyclotron Resonance-Mass Spectrometry and Gas Chromatography-Mass Spectrometry.

Castor oil is a traditional Chinese medicine containing a chemically complex mixture of triacylglycerols (TAGs). Herein, the TAGs in castor oil were analyzed in detail. First, the fatty acid composition of castor oil was examined via methylated derivatisation followed by gas chromatography-mass spectrometry (GC-MS). Then, using the fatty acid composition data, liquid chromatography-mass spectrometry (LC-MS) was applied to analyze the composition and relative content of TAGs. Nine TAGs were identified, wherein triricinolein (RRR) constituted ~81% of the total TAG content based on the peak areas. However, the TAGs in castor oil contain hydroxyl groups, which are incompatible with the equivalent carbon number (ECN) rule. Thus, an extended-ECN rule was expressed as E-ECN = CN (carbon number)-2·DB (double-bond number)-6·OH (hydroxyl group number) to characterize the retention of hydroxyl-containing TAGs in HPLC using a C18 column. Moreover, hydroxyl-containing TAGs may become dehydrated when analyzed using atmospheric pressure chemical ionization (APCI), which was confirmed via APCI Fourier transform-ion cyclotron resonance-mass spectrometry (FT-ICR-MS). Thus, the TAGs in castor oil were accurately identified through LC-MS together with FT-ICR-MS and GC-MS.

Tea Consumption and Longitudinal Change in High-Density Lipoprotein Cholesterol Concentration in Chinese Adults.

BACKGROUND: The relation between tea consumption and age-related changes in high-density lipoprotein cholesterol (HDL-C) concentrations remains unclear, and longitudinal human data are limited. The aim of current study was to examine the relation between tea intake and longitudinal change in HDL-C concentrations. METHODS AND RESULTS: Baseline (2006) tea consumption was assessed via a questionnaire, and plasma HDL-C concentrations were measured in 2006, 2008, 2010, and 2012 among 80 182 individuals (49±12 years of age) who did not have cardiovascular diseases or cancer, or did not use cholesterol-lowering agents both at baseline (2006) and during the follow-up period (2006-2012). The associations between baseline tea consumption and rate of change in HDL-C concentrations were examined using generalized estimating equation models. Tea consumption was inversely associated with a decreased rate of HDL-C concentrations (P-trend <0.0001) in the fully adjusted model. The adjusted mean difference in the HDL-C decreased rate was 0.010 (95% confidence interval, 0.008, 0.012) mmol/L per year for tea consumers versus nonconsumers (never or less than once/month group). Interactions between tea consumption and age, sex, lifestyle scores, and metabolic syndrome (all P-interaction <0.0001) were identified. The associations between greater tea consumption and slower decrease in HDL-C concentrations were more pronounced in men, individuals aged 60 or older, individuals with a lower lifestyle score, and individuals with metabolic syndrome (all P-trend <0.0001). CONCLUSIONS: Tea consumption was associated with slower age-related decreases in HDL-C concentrations during 6 years of follow-up. CLINICAL TRIAL REGISTRATION: URL: www.chictr.org. Unique identifier: ChiCTR-TNRC-11001489.

Application of ultra-high performance supercritical fluid chromatography for the determination of carotenoids in dietary supplements.

A quick and simple ultra-high performance supercritical fluid chromatography-photodiode array detector method was developed and validated for the simultaneous determination of 9 carotenoids in dietary supplements. The influences of stationary phase, co-solvent, pressure, temperature and flow rate on the separation of carotenoids were evaluated. The separation of the carotenoids was carried out using an Acquity UPC(2) HSS C18 SB column (150mm×3.0mm, 1.8µm) by gradient elution with carbon dioxide and a 1:2 (v:v) methanol/ethanol mixture. The column temperature was set to 35°C and the backpressure was 15.2MPa. Under these conditions, 9 carotenoids and the internal standard, ß-apo-8'-carotenal, were successfully separated within 10min. The correlation coefficients (R(2)) of the calibration curves were all above 0.997, the limits of detection for the 9 carotenoids were in the range of 0.33-1.08µg/mL, and the limits of quantification were in the range of 1.09-3.58µg/mL. The mean recoveries were from 93.4% to 109.5% at different spiking levels, and the relative standard deviations were between 0.8% and 6.0%. This method was successfully applied to the determination of 9 carotenoids in commercial dietary supplements.

Tyrosinase inhibitor screening in traditional Chinese medicines by electrophoretically mediated microanalysis.

A capillary-electrophoresis-based method for the screening of tyrosinase inhibitors in traditional Chinese medicines was developed. The method integrated electrophoretically mediated microanalysis with sandwich mode injection, partial filling, and rapid polarity switching techniques, and carried out on-column enzyme reaction and the separation of substrate and product. The conditions were optimized including the background electrolyte, mixing voltage, and the incubation time. Finally, the screening of nine standard natural compounds of traditional Chinese medicines was carried out. The inhibitors can be directly identified from the reduced peak area of the product compared to that obtained without any inhibitor. Chlorogenic acid (100 µM) showed inhibitory activity with the inhibitory percentage of 19.8%, while the other compounds showed no inhibitory activity. This method has great application potential in drug discovery from traditional Chinese medicines.

Screening of neuraminidase inhibitors from traditional Chinese medicine by transverse diffusion mediated capillary microanalysis.

A transverse diffusion mediated capillary microanalysis method has been developed for screening of neuraminidase inhibitors from traditional Chinese medicine. The enzyme, substrate and inhibitors were sequentially injected, mixed efficiently by transverse diffusion of laminar flow profiles, then incubated and separated in the same capillary. To enhance the mixing efficiency of reactants, running buffer was injected by alternately applying +5 kPa and -5 kPa at the capillary inlet and the procedure was repeated three times. The capillary electrophoresis (CE) separation conditions and reactants mixing conditions were optimized. Dual-wavelength detection was employed to eliminate the interference with natural compounds. The method has been applied to determine the kinetics constant of neuraminidase and screen 12 compounds from traditional Chinese medicine. Four compounds have been found to be positive for enzyme inhibition. The results are in good agreement with those reported in the literature. The method realized the mixing of substrate and enzyme with identical electrophoretic mobility. This novel CE method was simple, rapid, economic, and fully automated. Therefore, it was appropriate for neuraminidase inhibitors screening and could be extended to other high-throughput screening of active components from traditional Chinese medicine.

How and when predictability interacts with accentuation in temporally selective attention during speech comprehension.

The present study used EEG to investigate how and when top-down prediction interacts with bottom-up acoustic signals in temporally selective attention during speech comprehension. Mandarin Chinese spoken sentences were used as stimuli. We systematically manipulated the predictability and de/accentuation of the critical words in the sentence context. Meanwhile, a linguistic attention probe 'ba' was presented concurrently with the critical words or not. The results showed that, first, words with a linguistic attention probe elicited a larger N1 than those without a probe. The latency of this N1 effect was shortened for accented or lowly predictable words, indicating more attentional resources allocated to these words. Importantly, prediction and accentuation showed a complementary interplay on the latency of this N1 effect, demonstrating that when the words had already attracted attention due to low predictability or due to the presence of pitch accent, the other factor did not modulate attention allocation anymore. Second, relative to the lowly predictable words, the highly predictable words elicited a reduced N400 and enhanced gamma-band power increases, especially under the accented conditions; moreover, under the accented conditions, shorter N1 peak-latency was found to correlate with larger gamma-band power enhancement, which indicates that a close relationship might exist between early selective attention and later semantic integration. Finally, the interaction between top-down selective attention (driven by prediction) and bottom-up selective attention (driven by accentuation) occurred before lexical-semantic processing, namely before the N400 effect evoked by predictability, which was discussed with regard to the language comprehension models.