8-OHdG mediates the association of co-exposure to fifty-five typical endocrine-disrupting chemicals with renal function: a cross-section investigation in Southern Chinese adults.

Individual typical endocrine-disrupting chemicals (EDCs), including organophosphate triesters (OPEs), parabens, triclosan (TCS), bisphenols, benzophenones (BPs), phthalates (PAEs), and synthetic phenolic antioxidants (SPAs), are associated with renal dysfunction. However, the combined effects and underlying mechanisms of mixed EDC exposure on renal function remain unclear. Two hundred ninety-nine adult participants were enrolled in the cross-sectional survey conducted in Guangzhou, China. Urinary levels of 7 OPEs, 6 parabens, TCS, 14 bisphenols, 8 BPs, 15 PAEs, 4 SPAs, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were determined, and estimated glomerular filtration rate (eGFR) was served as the outcome index. We found elevated levels of diphenyl phosphate (DPP), bisphenol A (BPA), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-butyl phthalate (MBP) showed dose-responsive associations with eGFR decline, However, nonlinear associations were observed for bis(2-butoxyethyl) hydrogen phosphate (BBOEP), TCS, 4-hydroxybenzophenone (HBP), mono-n-pentyl phthalate (MnPP), and mono-benzyl phthalate (MBzP). The quantile-based g-computation model demonstrated that a quartile increase in the EDC mixture corresponded to a 0.383-SD decrease (95% CI - 0.658 ~ - 0.108, P = 0.007) in eGFR. Notably, BPA was identified as the primary contributor to this effect. Moreover, 8-OHdG mediated the eGFR decline associated with EDC mixtures with a mediation proportion of 25.49%. A sex-modified effect was also observed (P = 0.004), indicating that exposure to the mixture of EDC was linked to more pronounced renal dysfunction in females. Our novel findings suggest that exposure to a typical mixture of EDCs is associated with renal dysfunction in the general adult population of Southern China. Furthermore, 8-OHdG may play a role in the pathogenesis of EDC mixture-related renal dysfunction.

Empirical analysis of lead neurotoxicity mode of action and its application in health risk assessment.

The mode of action (MOA) framework is proposed to inform a biological link between chemical exposures and adverse health effects. Despite a significant increase in knowledge and awareness, the application of MOA in human health risk assessment (RA) remains limited. This study aims to discuss the adoption of MOA for health RA within a regulatory context, taking our previously proposed but not yet validated MOA for lead neurotoxicity as an example. We first conducted a quantitative weight of evidence (qWOE) assessment, which revealed that the MOA has a moderate confidence. Then, targeted bioassays were performed within an in vitro blood-brain barrier (BBB) model to quantitatively validate the scientific validity of key events (KEs) in terms of essentiality and concordance of empirical support (dose/temporal concordance), which increases confidence in utilizing the MOA for RA. Building upon the quantitative validation data, we further conducted benchmark dose (BMD) analysis to map dose-response relationships for the critical toxicity pathways, and the lower limit of BMD at a 5% response (BMDL5) was identified as the point of departure (POD) value for adverse health effects. Notably, perturbation of the Aryl Hydrocarbon Receptor (AHR) signaling pathway exhibited the lowest POD value, measured at 0.0062 µM. Considering bioavailability, we further calculated a provisional health-based guidance value (HBGV) for children's lead intake, determining it to be 2.56 µg/day. Finally, the health risk associated with the HBGV was assessed using the hazard quotient (HQ) approach, which indicated that the HBGV established in this study is a relative safe reference value for lead intake. In summary, our study described the procedure for utilizing MOA in health RA and set an example for MOA-based human health risk regulation.

Co-exposure of petrochemical workers to noise and mixture of benzene, toluene, ethylbenzene, xylene, and styrene: Impact on mild renal impairment and interaction.

Epidemiological evidence concerning effects of simultaneous exposure to noise and benzene, toluene, ethylbenzene, xylene, and styrene (BTEXS) on renal function remains uncertain. In 2020, a cross-sectional study was conducted among 1160 petrochemical workers in southern China to investigate effects of their co-exposure on estimated glomerular filtration rate (eGFR) and mild renal impairment (MRI). Noise levels were assessed using cumulative noise exposure (CNE). Urinary biomarkers for BTEXS were quantified. We found the majority of workers had exposure levels to noise and BTEXS below China's occupational exposure limits. CNE, trans, trans-muconic acid (tt-MA), and the sum of mandelic acid and phenylglyoxylic acid (PGMA) were linearly associated with decreased eGFR and increased MRI risk. We observed U-shaped associations for both N-acetyl-S-phenyl-L-cysteine (SPMA) and o-methylhippuric acid (2-MHA) with MRI. In further assessing the joint effect of BTEXS (ß, -0.164 [95% CI, -0.296 to -0.033]) per quartile increase in all BTEXS metabolites on eGFR using quantile g-computation models, we found SPMA, tt-MA, 2-MHA, and PGMA played pivotal roles. Additionally, the risk of MRI associated with tt-MA was more pronounced in workers with lower CNE levels (P = 0.004). Multiplicative interaction analysis revealed antagonisms of CNE and PGMA on MRI risk (P = 0.034). Thus, our findings reveal negative dose-effect associations between noise and BTEXS mixture exposure and renal function in petrochemical workers. With the exception of toluene, benzene, xylene, ethylbenzene, and styrene are all concerning pollutants for renal dysfunction. Effects of benzene, ethylbenzene, and styrene exposure on renal dysfunction were more pronounced in workers with lower CNE.

[Identification of Nitrate Source and Transformation Process in Shallow Groundwater Around Dianchi Lake].

Elucidating the main sources and transformation process of nitrate for the prevention and control of groundwater nitrogen pollution and the development and utilization of groundwater resources has great significance. To explore the current situation and source of nitrate pollution in shallow groundwater around the Dianchi Lake, 73 shallow groundwater samples were collected in the rainy season in 2020(October) and dry season in 2021(April). Using the hydrochemistry and nitrogen and oxygen isotopes(δ15N-NO3- and δ18O-NO3-), the spatial distribution, source, and transformation process of nitrate in shallow groundwater were identified. The contribution of nitrogen from different sources to nitrate in shallow groundwater was quantitatively evaluated using the isotope mixing model(SIAR). The results showed that in nearly 40.5% of sampling points in the shallow groundwater in the dry season, ρ(NO3--N) exceeded the 20 mg·L-1 specified in the Class Ⅲ water quality standard for groundwater(GB/T 14848), and in more than 47.2% of sampling points in the rainy season, ρ (NO3--N) exceeded 20 mg·L-1. The analysis results of nitrogen and oxygen isotopes and SIAR model showed that soil organic nitrogen, chemical fertilizer nitrogen, and manure and sewage nitrogen were the main sources of nitrate in shallow groundwater; these nitrogen sources contributed 13.9%, 11.8%, and 66.5% to nitrate in shallow groundwater in the dry season and 33.7%, 31.1%, and 25.9% in the rainy season, respectively. However, the contribution rate of atmospheric nitrogen deposition was only 8.5%, which contributed little to the source of nitrate in shallow groundwater in the study area. Nitrification was the leading process of nitrate transformation in shallow groundwater in the dry season, denitrification was the dominant process in the rainy season, and denitrification was more noticeable in the rainy season than that in the dry season.

Effects of coexposure to noise and mixture of toluene, ethylbenzene, xylene, and styrene (TEXS) on hearing loss in petrochemical workers of southern China.

Many harmful factors existing simultaneously with noise are reported to induce hearing impairment, such as organic solvents. However, the existing hearing safety limits and current risk assessment for hearing loss rely on single noise exposure. It is urgent to clarify the combined effect of noise and other harmful factors on hearing loss. Petrochemical workers are always exposed to noise and organic solvents, mainly benzene, toluene, ethylbenzene, xylene, and styrene (BTEXS), while the combined effect of their coexposure on hearing remains unclear. Herein we conducted a cross-sectional survey, measuring pure-tone audiometry of 1496 petrochemical workers in southern China. Participants exposed to BTEXS were 569, 524, 156, 452, and 177 respectively. Individual cumulative noise exposure (CNE) levels and BTEXS exposure were assessed. The average CNE was 93.27 ± 4.92 dB(A)·years, and the concentrations of BTEXS were far below the occupational exposure limits of China. Logistic regression analyses showed that CNE was consistently positively associated with hearing loss (HL) and high-frequency hearing loss (HFHL) but not related to speech-frequency hearing loss (SFHL). Compared with participants in the lowest quartile of CNE, those in the highest quartile showed an OR of 5.229 (95% CI: 3.179, 8.598) for HFHL. Two-pollutant model analysis indicated that TEXS exposure was positively associated with HL (OR 1.679, 95%CI 1.086, 2.597), SFHL (OR 2.440, 95%CI 1.255, 4.744), and HFHL (OR 1.475, 95%CI 1.077, 2.020). However, no interactions were observed between CNE and TEXS coexposure on hearing loss. In our study, covariates including smoking and drinking status, body mass index (BMI), ear protection and personal protective equipment, and use of earphone/headphone were adjusted. In conclusion, coexposure to noise and low-level TEXS could induce more severe damage on hearing function than exposure to each alone, especially SFHL. Therefore, petrochemical workers simultaneously exposed to noise and TEXS, even at low-level, should be included in hearing protection programs.

Prediction of phosphorus concentrations in shallow groundwater in intensive agricultural regions based on machine learning.

Excessive accumulation of phosphorus in soil profiles has become the main source of phosphorus in groundwater due to the application of phosphorus fertilizers in intensive agricultural regions (IARs). Elevated phosphorus concentrations in groundwater have become a global phenomenon, which places enormous pressure on the safe use of water resources and the safety of the aquatic environment. Currently, the prediction of pollutant concentrations in groundwater mainly focuses on nitrate nitrogen, while research on phosphorus prediction is limited. Taking the IARs approximately 8 plateau lakes in the Yunnan-Guizhou Plateau as an example, 570 shallow groundwater samples and 28 predictor variables were collected and measured, and a machine learning approach was used to predict phosphorus concentrations in groundwater. The performance of three machine learning algorithms and different sets of variables for predicting phosphorus concentrations in shallow groundwater was evaluated. The results showed that after all variables were introduced into the model, the R2, RMSE and MAE of support vector machine (SVM), random forest (RF) and neural network (NN) were 0.52-0.60, 0.101-0.108 and 0.074-0.081, respectively. Among them, the SVM model had the best prediction effect. The clay content and water-soluble phosphorus in soil and soluble organic carbon in groundwater had a high contribution to the prediction accuracy of the model. The prediction accuracy of the model with reduced number of variables showed that when the number of variables was equal to 6, the RF model had R2, RMSE and MAE values of 0.53, 0.108 and 0.074, respectively, and the number of variables increased again; there were small changes in R2, RMSE and MAE. Compared with the SVM and NN models, the RF model can achieve higher accuracy by inputting fewer variables.

[Shallow Groundwater Around Plateau Lakes: Spatiotemporal Distribution of Phosphorus and Its Driving Factors].

The extensive application of phosphorus fertilizers to croplands and the aggregation of towns and villages around plateau lakes has resulted in the continuous accumulation of phosphorus in the soil profile and the discharge of phosphorus pollutants, which causes phosphorus pollution in shallow groundwater around the lakes. The phosphorus entering the lake with shallow underground runoff in the region around the lake also affects the water quality safety of plateau lakes. The spatiotemporal differences in phosphorus concentrations in 452 shallow groundwater samples and the driving factors were analyzed by monitoring wells in croplands and residential areas around the eight lakes in Yunnan province during the rainy and dry seasons from 2019 to 2021. The results showed that seasonal changes and land use influenced phosphorus concentrations and their composition in shallow groundwater. The concentration of phosphorus in shallow groundwater in the rainy season was higher than that in the dry season, and it was also greater in cropland than that in residential areas. DTP was the dominant form of TP, accounting for 75%-81%, and DIP was the dominant form of DTP, accounting for 74%-80%. Nearly 30% of the samples around the eight lakes had TP concentrations exceeding the surface water Class Ⅲ standard (GB 3838); the exceeded rates of phosphorus in groundwater around the Erhai Lake (52%), Qiluhu Lake (45%), Xingyun Lake (42%), and Dianchi Lake (29%) were far higher than those of Yangzonghai Lake (16%), Fuxianhu Lake (13%), Chenghai Lake (6%), and Yilonghu Lake (5%). The key driving factors of phosphorus concentrations in shallow groundwater were water-soluble phosphorus (WEP), water content (MWC), soil organic matter (SOM), total nitrogen (TN), pH in the soil profile, and pH and groundwater level in the shallow groundwater (P<0.05). The increases in WEP, SOM, TN, and MWC in the soil and pH in groundwater significantly increased the concentrations of DIP and DTP in shallow groundwater, whereas the decrease in groundwater level significantly reduced the concentrations of DTP and DIP in the groundwater.

[Shallow Groundwater Around Plateau Lakes: Spatiotemporal Distribution of Nitrogen and Its Driving Factors].

Shallow groundwater around plateau lakes is one of the important sources of production and potable water. Shallow groundwater NO3--N pollution driven by factors such as surface nitrogen input load, rainfall, and irrigation is serious and threatens the water quality of plateau lakes. In order to identify the characteristics of nitrogen pollution and its driving factors in shallow groundwater, 463 shallow groundwater samples were collected from wells in farmland and residential areas around eight plateau lakes of Yunnan in the rainy and dry seasons in 2020 and 2021. The results showed that the average values of ρ(TN), ρ(NO3--N), ρ(ON), and ρ(NH4+-N) in shallow groundwater were 24.35, 15.15, 8.41, and 0.79 mg·L-1, respectively. Nearly 32% of the shallow groundwater samples around the eight lakes failed to meet the groundwater Class Ⅲ water quality requirements (GB/T 14848) of 20 mg·L-1 for NO3--N. Among them, the NO3--N concentration in the shallow groundwater around Erhai Lake, Qiluhu Lake, and Dianchi Lake had the highest rate of exceeding the standard, followed by that around Xingyunhu Lake, Yangzonghai Lake, Yilonghu Lake, Fuxianhu Lake, and Chenghai Lake as the smallest. Land use and seasonal changes affected the concentration and composition of various forms of nitrogen in shallow groundwater. The concentration of various forms of nitrogen in shallow groundwater in the farmland area was higher than that in the residential area. The nitrogen concentration in shallow groundwater in farmland was higher than that in residential areas. Except for NH4+-N, the concentration of various forms of nitrogen in shallow groundwater in the rainy season was higher than that in the dry season. NO3--N was the main nitrogen form in shallow groundwater; the fraction of TN was 57%-68%, and the fraction of ON was 27%-38%. The EC, DO, ORP, and T in shallow groundwater were the key factors reflecting or affecting the concentration of various forms of nitrogen in shallow groundwater, whereas soil factors had a weak impact on the concentration of various forms of nitrogen in shallow groundwater.

Relational integration predicted numerical inductive reasoning: ERP Evidence from the N400 and LNC.

As relational integration performance can be used to predict reasoning ability, the present study aimed to provide electrophysiological evidence for numerical inductive reasoning. Number series with two levels of relational complexity were utilized, including simple and hierarchical problems (such as "15-16-17" versus "15-16-18"). Two tasks were adopted: a relational integration task that required to determine whether the numerical relations were changed across numbers; a number series task that required to determine whether a hidden rule was acquired (Experiment 1) or to predict the subsequent number (Experiment 2), whose phases were divided as rule searching, rule discovery, and rule following. The event-related potential (ERP) results of both experiments indicated that, in contrast to simple problems, hierarchical problems triggered enhanced N400 and late negative component (LNC), reflecting numerical fact retrieval, and generalizing novel hypotheses about the hidden rules by integrating adjacent numerical relations, respectively; relational integration showed similar N400 and LNC activation patterns to rule discovery (Experiment 1) or rule searching (Experiment 2). Additionally, the N400 and LNC elicited by relational integration showed strong positive correlations and even were able to predict the ones triggered by rule discovery (Experiment 1) or rule searching (Experiment 2). Therefore, the results supported the role of relational integration in numerical inductive reasoning and thereby in intelligence.

How types of prior knowledge and task properties impact the category-based induction: diverging evidence from the P2, N400, and LPC effects.

Category-based induction task was combined with ERP to unravel whether prior knowledge and property interact when inferring on genes or diseases. Larger P2 amplitudes for near taxonomic/causal distances relative to far ones, as well as larger LPC for taxonomic relation relative to thematic relation, are found in both gene and disease tasks. However, smaller N400 is found for taxonomic relation in gene task and thematic relation in disease task, respectively, and larger LPC at 700-850 ms for near taxonomic distance in the gene task and near causal distance in the disease task. These results suggested that the category-based inductive reasoning is context-sensitive, and there may be four stages of category-based inductive reasoning: the early automatic comparison of features/relations (P2), features/relations generalization process (N400), the extraction of common relationship/rule (LPC at 550-700 ms), the inference generation (LPC at 700-850 ms).

Task relevance effect on number/shape conflict detection in the number-matching task: An ERP study.

It is debatable whether the task relevance effect on a conflict occurs in the detection or in the inhibition underlying sequential matching. To explore this issue, three types of number pairs, identical (e.g., 12, 12), conserved (e.g., 12, ), and non-conserved (e.g., 12, 15) pairs, were displayed to be judged as perceptually (identical shape condition) or quantitatively (identical value condition) the same. Both error rates and RTs for the three types of number pairs showed different patterns to detect perceptual mismatch in the identical shape condition and number inequivalence in the identical value conditions. The event-related potential (ERP) results showed that increased N200 and N400 as well as decreased P300 were triggered by the conserved and non-conserved pairs in contrast to identical pairs in the identical shape condition and by the non-conserved pairs relative to the conserved and identical pairs in the identical value condition. These results showed that task-relevant mismatches were attended to and detected in both conditions. Therefore, for the task-relevance effect on a conflict, attention is selectively directed to task-relevant features rather than inhibiting task-irrelevant conflict.

Targeting epidermal growth factor-overexpressing triple-negative breast cancer by natural killer cells expressing a specific chimeric antigen receptor.

OBJECTIVES: Traditional cancer therapy and regular immunotherapy are ineffective for treating triple-negative breast cancer (TNBC) patients. Recently, chimeric antigen receptor-engineered natural killer cells (CAR NK) have been applied to target several hormone receptors on different cancer cells to improve the efficacy of immunotherapy. Furthermore, epidermal growth factor receptor (EGFR) is a potential therapeutic target for TNBC. Here, we demonstrated that EGFR-specific CAR NK cells (EGFR-CAR NK cells) could be potentially used to treat patients with TNBC exhibiting enhanced EGFR expression. MATERIALS AND METHODS: We investigated the cytotoxic effects of EGFR-CAR NK cells against TNBC cells in vitro and in vivo. The two types of EGFR-CAR NK cells were generated by transducing lentiviral vectors containing DNA sequences encoding the single-chain variable fragment (scFv) regions of the two anti-EGFR antibodies. The cytotoxic and anti-tumor effects of the two cell types were examined by performing cytokine release and cytotoxicity assays in vitro, and tumor growth assays in breast cancer cell line-derived xenograft (CLDX) and patient-derived xenograft (PDX) mouse models. RESULTS: Both EGFR-CAR NK cell types were activated by TNBC cells exhibiting upregulated EGFR expression and specifically triggered the lysis of the TNBC cells in vitro. Furthermore, the two EGFR-CAR NK cell types inhibited CLDX and PDX tumors in mice. CONCLUSIONS: This study suggested that treatment with EGFR-CAR NK cells could be a promising strategy for TNBC patients.

Neonatal DEX exposure leads to hyperanxious and depressive-like behaviors as well as a persistent reduction of BDNF expression in developmental stages.

Brain-derived neurotrophic factor (BDNF), which regulates the neuronal survival, differentiation and synaptic plasticity, has been proved to play a critical role in the pathology and treatment of several psychiatric disorders including depression. Dexamethaone (DEX) is indicated for a number of conditions in perinatal medicine, however, the long-term impact of early-life DEX exposure on BDNF expression in hippocampus remains unknown. Here we found that neonatal DEX(ND) exposure leads to insignificant change of BDNF expression levels in the adulthood, albeit increased hyperanxious and depressive-like behaviors. However, the bdnf mRNA and BDNF protein levels were significantly reduced in all the hippocampal subregions during the developmental stages, including the perinatal period and puberty. We conclude that early life DEX exposure leads to a persistent disturbance of BDNF signaling during the developmental stages, which might be associated with the life-long impairment of hippocampal function.

N400/frontal negativity reveals the controlled processes of taxonomic and thematic relationships in semantic priming for artifacts.

Recent studies show that taxonomic and thematic relationships are functionally and neurologically dissociated; however, there remain some discrepancies due to inconsistencies in definitions, task properties, and concept domains. This issue was further explored via the semantic priming paradigm with a long SOA of 600 ms while controlling for perceptual or functional features of artifacts involved across taxonomic and thematic relationships. Six conditions were compared: perceptual relationship (axe-helve), functional relationship (axe-wood), perceptual classification (axe-hammer), functional classification (axe-saw), unrelated condition (axe-skates), and nonword (axe-derf) conditions. Behavioral priming effects are found for all related conditions relative to unrelated conditions except for perceptual relationships, whereas semantic priming effects (smaller N400 amplitude) are found for functional relationships and perceptual classification relative to unrelated conditions but not for perceptual relationships and functional classification, indicating perceptual features are less important than functional features for artifacts. Furthermore, the frontal negativity elicited by functional relationships is smaller than all other related conditions at 400-550 ms, while it is only smaller than functional classification at 550-650 ms. These results indicate that, besides different features, taxonomic and thematic relationships are dissociated to organize object knowledge, which is primarily fuelled by feature processing, with taxonomic, or thematic, relationships further embedded with such sensory, or functional, features.

EGFR-specific CAR-T cells trigger cell lysis in EGFR-positive TNBC.

Triple-negative breast cancer (TNBC) is an aggressive cancer subtype for which effective therapies are lacking. Epidermal growth factor receptor (EGFR) is overexpressed in various types of TNBC cells, and several EGFR-specific immunotherapies have been used to treat cancer patients. Chimeric antigen receptor engineered T (CAR-T) cells have also been used as cancer therapies. In this study, we generated two types of EGFR-specific CAR-modified T cells using lentiviral vectors with DNA sequences encoding the scFv regions of two anti-EGFR antibodies. The cytotoxic and antitumor effects of these CAR-modified T cells were examined in cytokine release and cytotoxicity assays in vitro and in tumor growth assays in TNBC cell line- and patient-derived xenograft mouse models. Both types of EGFR-specific CAR-T cells were activated by high-EGFR-expressing TNBC cells and specifically triggered TNBC cell lysis in vitro. Additionally, the CAR-T cells inhibited growth of cell-line- and patient-derived xenograft TNBC tumors in mice. These results suggest that EGFR-specific CAR-T cells might be a promising therapeutic strategy in patients with high-EGFR-expressing TNBC.

Common and distinct brain responses to detecting top-down and bottom-up conflicts underlying numerical inductive reasoning.

Complex reasoning problems are commonly influenced by a combination of top-down and bottom-up conflicts; however, the common and distinct brain responses to the two types of conflicts have remained unclear. Participants were required to identify the hidden rules in a number series completion task, which included identity condition (e.g., 13, 13, 13), perceptual mismatch condition (bottom-up conflict, e.g., 13 13 +≡), and relational mismatch condition (top-down conflict, e.g., 13 13 14). The ERP results showed that (a) both the perceptual and relational mismatch conditions triggered greater P200, N200, P300, and late positive component than the identity condition, reflecting attention reallocation, perceptual template deviations, feelings of uncertainty, and working memory updating, respectively, and (b) smaller N400 and decreased late negative component were found in the relational mismatch condition in contrast to other conditions, which suggested that changing number values violated rule expectancy as top-down conflict. Therefore, multiple strategies were utilized to detect the conflicts underlying complex reasoning problems.

P300 and positive slow waves reveal the plausibility in inductive reasoning.

Category-based induction is an advanced cognitive function that is based on our category-level knowledge. Previous findings have recognized the distance effect in category-based induction: Inductive strength is affected by the hierarchical distance between the premises and conclusions. However, the neural mechanisms underlying this effect require elucidation. In the present study, we investigated the neural mechanisms of the distance effect by using EEG technology and a new experimental paradigm-category-based induction. In this paradigm, we used three hierarchical levels of categories-the subordinate category, the basic category, the superordinate category-and an irrelevant category. We further used these categories to create four types of trial that varied in the hierarchical distance between the premise and the conclusion: the subordinate-basic, the basic-superordinate, the subordinate-superordinate, and the irrelevant-superordinate trials. In each trial, participants judged the probability that the conclusion category had the same property as the premise category. Our behavioral results revealed that people responded more slowly in the irrelevant-superordinate trials than in the basic-superordinate and the subordinate-basic trials. Our ERP results showed that the irrelevant-superordinate trials elicited smaller P300 (250-500 ms) amplitudes than did the subordinate-basic and the basic-superordinate trials. In addition, the subordinate-superordinate trials elicited smaller P300 and PSW (700-998 ms) amplitudes than did the subordinate-basic and the basic-superordinate combinations. These findings indicate that the amplitudes of P300 and PSW may reflect the distance effect in inductive reasoning: The further the premise-conclusion hierarchical distance, the lower the inductive strength, and thus the smaller the P300 and PSW amplitudes.

Oncogenic functions of protein kinase D2 and D3 in regulating multiple cancer-related pathways in breast cancer.

Protein Kinase D (PKD) family contains PKD1, PKD2, and PKD3 in human. Compared to consistent tumor-suppressive functions of PKD1 in breast cancer, how PKD2/3 functions in breast cancer are not fully understood. In the current study, we found that PKD2 and PKD3 but not PKD1 were preferentially overexpressed in breast cancer and involved in regulating cell proliferation and metastasis. Integrated phosphoproteome, transcriptome, and interactome showed that PKD2 was associated with multiple cancer-related pathways, including adherent junction, regulation of actin cytoskeleton, and cell cycle-related pathways. ELAVL1 was identified as a common hub-node in networks of PKD2/3-regulated phosphoproteins and genes. Silencing ELAVL1 inhibited breast cancer growth in vitro and in vivo. Direct interaction between ELAVL1 and PKD2 or PKD3 was demonstrated. Suppression of PKD2 led to ELAVL1 translocation from the cytoplasm to the nucleus without significant affecting ELAVL1 expression. Taken together, we characterized the oncogenic functions of PKD2/3 in breast cancer and their association with cancer-related pathways, which shed lights on the oncogenic roles and mechanisms of PKDs in breast cancer.

The rule expectancy effect on the electrophysiological correlates underlying numerical rule acquisition.

The present study aimed to provide electrophysiological evidence about acquiring complex numerical rules when unexpected numbers were presented. Hence, we compared the neural correlates underlying the acquisition of unexpected complex rules (e.g., 12, 14, 18, 24) compared to expected simple rules (e.g., 12, 14, 16, 18). The event-related potential (ERP) results for the rule acquisition process for the third numbers showed that, in contrast to expected simple rules, unexpected complex rules elicited: an enhanced N200, reflecting the detection of a conflict between the expected numbers and the displayed numbers; a decreased P300, indicating a feeling of uncertainty accompanied by identifying numerical regularity; and an increased LPC, reflecting the working-memory updating caused by expectancy violation and rule acquisition. These results describe the precise time course of acquiring novel and complex rules when unexpected numbers were presented.

The time course of indirect moral judgment in gossip processing modulated by different agents.

Previous studies have investigated personal moral violations with different references (i.e., the protagonists in moral scenarios are the participants themselves or unknown other individuals). However, the roles of various agents in moral judgments have remained unclear. In the present study, ERPs were used to investigate moral judgments when the participants viewed gossip that described (im)moral behaviors committed by different agents (self, friend, celebrity). The results demonstrate that the P2 and late positive component (LPC) correspond to two successive processes of indirect moral judgment when individuals process gossip. Specifically, the P2 amplitude in the celebrity condition was more sensitive in distinguishing immoral behaviors from moral behaviors than that in the other two conditions, whereas the moral valence effect on the LPC was predominately driven by the self-reference. These findings expand our current understanding of moral judgments in a gossip evaluation task and demonstrate that the early processing of gossip depends on both the entertainment value of the agent and the salience of moral behaviors. Processing in the later stage reflects reactions to intensified affective stimuli, or reflects cognitive effort that was required to resolve the conflict between negative gossip about self and the self-positivity bias.