Increased LACTB2 Expression Regulates Oxidative Phosphorylation and mTORC1 Signaling of Colorectal Cancer.

This study aimed to investigate the mechanisms of LACTB2 in colorectal cancer (CRC). Microarrays and sequencing data of CRC were acquired from UCSC Xena, GTEx, Gene Expression Omnibus, and TCGA. Pooled analysis of the mRNA expression of LACTB2 in CRC was performed using Stata software. The protein expression of LACTB2 in CRC tissues was evaluated by immunohistochemistry. The relationship between immune cell infiltration and LACTB2 expression was investigated using CIBERSORT. The potential signaling pathways and biological mechanisms of LACTB2 were explored using GSEA, KEGG, and GO. Subsequently, further screening of small molecular compounds with potential therapeutic effects on CRC was conducted through the HERB database, followed by molecular docking studies of these compounds with the LACTB2 protein. The integration and analysis of expression data obtained from 2294 CRC samples and 1286 noncancerous colorectal samples showed that LACTB2 was highly expressed in CRC. Immunohistochemistry performed on in-house tissue samples confirmed that LACTB2 protein expression was upregulated in CRC. CIBERSORT revealed lower B cell infiltration levels in the high LACTB2 expression group than in the low expression group. GO, KEGG, and GSEA analyses showed that LACTB2 expression and genes positively correlating with it were mainly related to DNA synthesis and repair, mitochondrial translational elongation and translational termination, phosphorylation, and mTORC1 signaling. Finally, molecular docking simulations confirmed the ability of quercitin to target and bind to LACTB2. This is the first study to demonstrate that LACTB2 is upregulated in CRC. LACTB2 promotes colorectal tumorigenesis and tumor progression.

The neural representation of metacognition in preferential decision-making.

Humans regularly assess the quality of their judgements, which helps them adjust their behaviours. Metacognition is the ability to accurately evaluate one's own judgements, and it is assessed by comparing objective task performance with subjective confidence report in perceptual decisions. However, for preferential decisions, assessing metacognition in preference-based decisions is difficult because it depends on subjective goals rather than the objective criterion. Here, we develop a new index that integrates choice, reaction time, and confidence report to quantify trial-by-trial metacognitive sensitivity in preference judgements. We found that the dorsomedial prefrontal cortex (dmPFC) and the right anterior insular were more activated when participants made bad metacognitive evaluations. Our study suggests a crucial role of the dmPFC-insula network in representing online metacognitive sensitivity in preferential decisions.

Wogonin inhibits the migration and invasion of fibroblast-like synoviocytes by targeting PI3K/AKT/NF-κB pathway in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is currently an autoimmune inflammatory disease with an unclear pathogenesis. Fibroblast-like synoviocytes (FLSs) have tumor-like properties, and their activation and secretion of pro-inflammatory factors are important factors in joint destruction. Wogonin (5,7-dihydroxy-8-methoxyflavone), a natural flavonoid isolated from Scutellaria baicalensis root, has been shown to have significant anti-inflammatory, anti-oxidative stress, and anti-tumor effects in a variety of diseases. However, the role of wogonin in RA has not yet been demonstrated. PURPOSE: To investigate the inhibitory effect of wogonin on the invasive behavior of fibroblast-like synoviocytes and to explore the mechanism of action of wogonin in RA. METHODS: CCK-8, EdU, cell migration and invasion, immunofluorescence staining, RT-qPCR, and protein blot analysis were used to study the inhibitory effects of wogonin on migration, invasion, and pro-inflammatory cytokine overexpression in the immortalized rheumatoid synovial cell line MH7A. The therapeutic effects of wogonin were validated in vivo using arthritis scores and histopathological evaluation of collagen-induced arthritis mice. RESULTS: Wogonin inhibited the migration and invasion of MH7A cells, reduced the production of TNF-α, IL-1ß, IL-6, MMP-3 and MMP-9, and increased the expression of IL-10. Moreover, wogonin also inhibited the myofibrillar differentiation of MH7A cells, increased the expression of E-cadherin (E-Cad) and decreased the expression of α-smooth muscle actin (α-SMA). In addition, wogonin treatment effectively ameliorated joint destruction in CIA mice. Further molecular mechanism studies showed that wogonin treatment significantly inhibited the activation of PI3K/AKT/NF-κB signaling pathway in TNF-α-induced arthritic FLSs. CONCLUSION: Wogonin effectively inhibits migration, invasion and pro-inflammatory cytokine production of RA fibroblast-like synoviocytes through the PI3K/AKT/NF-κB pathway, and thus wogonin, as a natural flavonoid, has great potential for treating RA.

The impact of feedback on metacognition: Enhancing in easy tasks, impeding in difficult ones.

Metacognition refers to the ability to monitor and introspect upon cognitive performance. Abundant research suggests that individual metacognition is easily affected by feedback in daily life, but how feedback affects metacognition in perceptual decision-making remains unclear. Here we investigated how trial-by-trial feedback shapes perceptual metacognition in two experiments with either high (n = 82) or low difficulty (n = 90). Participants were randomly divided into a feedback group in which participants received trial-by-trial performance feedback or a no-feedback group. Results showed that, in the high-difficulty task, participants in the feedback group revealed inferior metacognitive performance than the no-feedback group, manifested as decreased metacognitive efficiency while controlling for performance sensitivity. In the low-difficulty task, however, participants in the feedback group had higher metacognitive efficiency than the no-feedback group. The distinct patterns of findings in the two experiments indicate that whether feedback promotes or impedes metacognition is adjusted by task difficulty.

A retrospective cohort study on the efficacy and safety for combination therapy of immunotherapy, targeted agent, and chemotherapy versus immunochemotherapy or chemotherapy alone in the first-line treatment of advanced biliary tract carcinoma.

Background: A paucity of effective treatment for biliary tract carcinoma (BTC) has necessitated the investigation into new therapies. As combinations of targeted therapy with immunotherapy are well-established in hepatocellular carcinoma, the GEMOX chemotherapy (gemcitabine and oxaliplatin) is the standard treatment for BTC. This study aimed to evaluate the efficacy and safety of immunotherapy in combination with targeted agent and chemotherapy in advanced BTC. Methods: Patients who were pathologically identified advanced BTC and had received gemcitabine-based chemotherapy alone or in combination with anlotinib, and/or anti-programmed cell death protein-1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors such as camrelizumab as first-line treatment were retrospectively screened from The First Affiliated Hospital of Guangxi Medical University from February 2018 to August 2021. The outcomes included objective response rate (ORR), median overall survival (OS), and median progressive-free survival (PFS). Adverse events (AEs) were assessed according to the NCI-CTCAE v. 4.03. Patients were followed up weekly. Results: A total of 35 patients were enrolled in this study: 11 patients treated with PD-1/PD-L1 inhibitor plus anlotinib and gemcitabine (arm A), 12 patients with the GEMOX combined with PD-1/PD-L1 inhibitor (arm B), and 12 patients with GEMOX (arm C). With a median follow-up time of 31.9 months (range, 23.8-39.7 months), the median OS was 16.8 months [95% confidence interval (CI): 7.0-not reached], 11.8 months (95% CI: 7.2-31.7 months), and 11.6 months (95% CI: 7.3-18.0 months) in arms A, B, and C, respectively (P=0.298). The median PFS was 16.8 months (95% CI: 7.0-NR), 6.0 months (95% CI: 5.1-8.7 months), and 6.3 months (95% CI: 4.6-7.0 months) in arms A, B, and C, respectively. The ORR were 63.6% in arm A, 33.3% in arm B, and 25.0% in arm C. AEs of all grades occurred in 33 (94.3%) patients. Grade 3-4 AEs in all patients included neutrophil count decrease (14.3%), aspartate aminotransferase increase (8.6%), alanine aminotransferase increase (8.6%), fatigue (5.7%), and blood bilirubin increase (5.7%). Conclusions: Anti-PD-1/PD-L1 immunotherapy in combination with anlotinib and gemcitabine showed promising efficacy and an acceptable safety profile for the BTC patients included in this study.

Mechanism underlying the action of Duanteng-Yimu Tang in regulating Treg/Th17 imbalance and anti-rheumatoid arthritis.

Background: Rheumatoid arthritis (RA) is a chronic immune disease characterised by synovitis and cartilage destruction. Currently, many patients experience poor remission after new antirheumatic drug treatments. Duanteng-Yimu Tang (DTYMT), a traditional Chinese medicine, is effective in the treatment of RA. In this research, we designed to investigate the anti-RA effects of DTYMT and explore its potential mechanisms. Methods: Network pharmacology was adopted to explore the main pathways of DTYMT in patients with RA. Collagen-induced arthritis models of male DBA/1 mice were established, and their histopathological changes were observed by hematoxylin-eosin staining and micro-CT. qRT-PCR was performed to detect the expression of Foxp3 and RORγt in the serum and synovial tissue and IL-17, IL-1ß, TNF-α, and IL-10 mRNA in vivo. The proliferation and invasion of synovial cells were analyzed using Cell Counting Kit-8 and transwell assays, respectively. The ratio of T helper 17 (Th17) to regulatory T (Treg) cells was analyzed by flow cytometry. Results: Network pharmacology analysis revealed that Th17 cell differentiation may be the key pathway of DTYMT in RA. DTYMT ameliorated joint damage, inhibited RORγt expression, and increased Foxp3 expression in CIA mice. DTYMT significantly decreased IL-1ß, IL-17, and TNF-α mRNA levels, and increased IL-10 mRNA levels in IL-6-induced cells. Additionally, DTYMT inhibited Th17 cell differentiation and promoted Treg cell production, thus improving the Treg/Th17 imbalance. DTYMT also inhibited the proliferation, migration, and invasion of RA fibroblast-like synovial cells. Conclusions: These results indicate that DTYMT could regulate the Treg/Th17 cell balance, which is a possible mechanism of DTYMT in treating RA.

Childhood trauma and suicidal ideation among Chinese adolescents: The mediating effects of character strengths and perceived stress.

WHAT IS KNOWN ON THE SUBJECT?: Prior research has demonstrated that childhood trauma can increase adolescents' suicidal ideation, and perceived stress plays a mediating role in the relationship between childhood trauma and adolescents' suicidal ideation. Character strengths, which are trait-like positive personality characteristics, have also been found to be closely related to decreased stress and suicidal ideation. However, it is unclear whether character strengths act as a transfer mechanism that links childhood traumatic experiences with perceived stress and eventually suicidal ideation. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: This study found that character strengths and perceived stress serially mediated the association between childhood trauma and suicidal ideation. Specifically, childhood trauma was associated with inferior character strengths, and the impaired character strengths further triggered high perceived stress, which was finally linked to a heightened risk of suicidal ideation. This study provided important theoretical implications for preventing suicidal risk among adolescents who are exposed to traumatic events during childhood. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: This study highlighted the roles of character strengths and perceived stress in the relationship between childhood traumatic experiences and suicidal ideation, which provided suggestions for designing nursing interventions to reduce adolescents' suicidal ideation, especially for those with traumatic childhood experiences. In addition to family nursing, school-based regular monitoring and interventions of character strengths and perceived stress are necessary. ABSTRACT: Aim This study sought to examine the mediating effects of character strengths and perceived stress on the relationship between childhood trauma and suicidal ideation among adolescents. Methods A cross-sectional survey was conducted on a sample of 1069 Chinese adolescents. The Chinese versions of the Suicidal Ideation Scale, Childhood Trauma Questionnaire, Perceived Stress Scale and Character Scale for Adolescents were used to assess adolescents' suicidal ideation, childhood trauma, perceived stress and character strengths. Results The findings showed that childhood trauma influenced suicidal ideation directly and indirectly via perceived stress. Moreover, character strengths and perceived stress serially mediated the association between childhood trauma and suicidal ideation, implying that childhood trauma was associated with inferior character strengths, and the impaired character strengths further triggered high perceived stress, which was finally linked to a heightened risk of suicidal ideation. Conclusions This study highlighted the joint contribution of childhood trauma, character strengths and perceived stress to suicidal ideation, providing theoretical and practical implications to guide mental health nurses to reduce the suicide risk among adolescents. Implications for Practice These findings highlighted the importance of developing character strengths and stress-coping strategies. Family nursing and school-based regular monitoring and interventions of character strengths and perceived stress are necessary among adolescents who exposed to a high level of childhood trauma experiences to reduce their suicidal ideation and foster mental health.

Pain Empathy and Its Association with the Clinical Pain in Knee Osteoarthritis Patients.

Objective: Knee osteoarthritis (KOA) is a painful chronic disorder. Evidence has shown that a history of chronic pain plays an important role in shaping empathy. Empathy, a valuable indicator of social functioning that refers to an individual's ability to share the experiences of others, however, has been overlooked in KOA patients. This study aimed to investigate empathy and its association with clinical pain in KOA patients. Methods: KOA patients (n=47) and healthy controls (HCs, n=44) completed two empathy-for-pain tasks: a pain judgment task in which participants judged whether a person in an image felt pain or not, and a pain rating task in which they estimated pain intensity for themselves and others. The Interpersonal Reactivity Index was used to measure participants' trait empathy, and clinical severity and psychological factors were assessed using relevant instruments. Results: Compared to HCs, KOA patients showed higher accuracy when judging pain and non-pain images and reported overall higher pain intensity when rating for themselves and others. KOA patients also showed greater personal distress than HCs in terms of their self-reported empathy. Moreover, pain catastrophizing particularly mediated the relationship between pain severity and pain ratings for others, and depression, anxiety, and pain catastrophizing all mediated the association between pain severity and empathy-induced personal distress. Conclusion: These findings suggest that patients with KOA have increased empathy, demonstrated by elevated sensitivity to pain-related scenes and intense emotional responses.

A cohesin-associated gene score may predict immune checkpoint blockade in hepatocellular carcinoma.

Stromal antigen 1 (STAG1), a component of cohesion, is overexpressed in various cancers, but it is unclear whether it has a role in the transcriptional regulation of hepatocellular carcinoma (HCC). To test this hypothesis, here, we screened global HCC datasets and performed multiscale embedded gene co-expression network analysis to identify the potential functional modules of differentially expressed STAG1 co-expressed genes. The putative transcriptional targets of STAG1 were identified using chromatin immunoprecipitation followed by high-throughput DNA sequencing. The cohesin-associated gene score (CAGS) was quantified using the The Cancer Genome Atlas HCC cohort and single-sample gene set enrichment analysis. Distinct cohesin-associated gene patterns were identified by calculating the euclidean distance of each patient. We assessed the potential ability of the CAGS in predicting immune checkpoint blockade (ICB) treatment response using IMvigor210 and GSE78220 cohorts. STAG1 was upregulated in 3313 HCC tissue samples compared with 2692 normal liver tissue samples (standard mean difference = 0.54). A total of three cohesin-associated gene patterns were identified, where cluster 2 had a high TP53 mutated rate and a poor survival outcome. Low CAGS predicted a significant survival advantage but presaged poor immunotherapy response. Differentially expressed STAG1 co-expression genes were enriched in the mitotic cell cycle, lymphocyte activation, and blood vessel development. PDS5A and PDGFRA were predicted as the downstream transcriptional targets of STAG1. In summary, STAG1 is significantly upregulated in global HCC tissue samples and may participate in blood vessel development and the mitotic cell cycle. A cohesin-associated gene scoring system may have potential to predict the ICB response.

The Effect of CRHBP rs10062367 Polymorphism and Parenting Styles on Internalizing Problems in Preschoolers: The Moderating Effect of Sensory Processing Sensitivity.

The present study aimed to examine how CRHBP rs10062367 polymorphism interacted with parenting styles and sensory processing sensitivity (SPS) to impact on preschoolers' internalizing problems. A total of 446 preschoolers (Mage = 4.55, SD = 1.07) participated in the study and their saliva were extracted to genotype the CRHBP rs10062367 polymorphism, and their parents were invited to complete a battery of questionnaires to assess parenting styles, preschoolers' SPS, and internalizing problems. Results indicated that high SPS preschoolers with A allele exhibited fewer internalizing problems under the condition of positive parenting while they exhibited more internalizing problems under the condition of negative parenting. The findings provide support for the Differential Susceptibility Model/Biological Sensitivity to Context Theory that A allele of rs10062367 and high SPS might be the "susceptibility markers" of children to environments.

Blunted reward prediction error signals in internet gaming disorder.

BACKGROUND: Internet gaming disorder (IGD) is a type of behavioural addictions. One of the key features of addiction is the excessive exposure to addictive objectives (e.g. drugs) reduces the sensitivity of the brain reward system to daily rewards (e.g. money). This is thought to be mediated via the signals expressed as dopaminergic reward prediction error (RPE). Emerging evidence highlights blunted RPE signals in drug addictions. However, no study has examined whether IGD also involves alterations in RPE signals that are observed in other types of addictions. METHODS: To fill this gap, we used functional magnetic resonance imaging data from 45 IGD and 42 healthy controls (HCs) during a reward-related prediction-error task and utilised a psychophysiological interaction (PPI) analysis to characterise the underlying neural correlates of RPE and related functional connectivity. RESULTS: Relative to HCs, IGD individuals showed impaired reinforcement learning, blunted RPE signals in multiple regions of the brain reward system, including the right caudate, left orbitofrontal cortex (OFC), and right dorsolateral prefrontal cortex (DLPFC). Moreover, the PPI analysis revealed a pattern of hyperconnectivity between the right caudate, right putamen, bilateral DLPFC, and right dorsal anterior cingulate cortex (dACC) in the IGD group. Finally, linear regression suggested that the connection between the right DLPFC and right dACC could significantly predict the variation of RPE signals in the left OFC. CONCLUSIONS: These results highlight disrupted RPE signalling and hyperconnectivity between regions of the brain reward system in IGD. Reinforcement learning deficits may be crucial underlying characteristics of IGD pathophysiology.

Efficacy and Safety of First-Line Chemotherapies for Patients With Advanced Biliary Tract Carcinoma: A Systematic Review and Network Meta-Analysis.

BACKGROUND: At present, chemotherapy is still the primary treatment for advanced biliary tract carcinoma, but it is challenging to balance the efficacy and side effects. Network meta-analysis (NMA) is a better way to identify the protocol, and the advantage is that it can be combined with direct and indirect evidence to judge the best treatment regimens. Therefore, we conducted NMA on the searched randomized controlled trials (RCTs). METHODS: NMA was conducted regarding the searched RCTs by comparing progression-free survival (PFS), overall survival (OS), objective remission rates (ORRs), and adverse events (AEs) of different chemotherapy protocols. RESULTS: We screened 24 studies that met the inclusion criteria for further analysis. Compared with other regimens, the best supportive care (BSC) or FUFA protocol has a worse OS. Folfox4, GEMOX+erlotinib, and C+GEMOX can improve patients' PFS compared with BSC. Patients receiving GP+cediranib protocol have higher ORRs. There was reduced neutropenia grade ≥3 when adopting GP+cediranib, GS, C+GEMOX, RAM+GP, and MER+GP than when using FUFA protocol. The probability of vomiting of XELOX is lower than that of GEM+XELOX. There is a lower diarrhea incidence of XELOX than that of GEMOX+erlotinib. The results of cluster grade analysis illustrated that GEMOX+erlotinib owned a higher ORR and a higher surface under the cumulative ranking (SUCRA) of neutropenia and vomiting but also had a lower SUCRA of diarrhea and fatigue. Meanwhile, both GEMOX and C+GEMOX have a better ORR and a higher AE SUCRA. CONCLUSION: The NMA demonstrated that chemotherapy combined with targeted therapy has better efficacy and lower incidence of AEs than chemotherapy alone.

Efficacy and biomarker exploration of camrelizumab combined with apatinib in the treatment of advanced primary liver cancer: a retrospective study.

This study was to explore the efficacy and safety of camrelizumab combined with apatinib in patients with advanced liver cancer. Moreover, the relationship between peripheral blood parameters and tumor response rate was also investigated. Patients with unresectable or recurrent primary liver cancer (PLC) who received treatment from July 2019 to July 2020 in the First Affiliated Hospital of Guangxi Medical University were included in this single-center retrospective study. The patients were treated with camrelizumab (200 mg, intravenous q2w) plus apatinib (250 mg, oral qd) until the occurrence of disease progression or unbearable toxicity. All the patients underwent blood routine test and detection of lactate dehydrogenase and serum albumin levels before treatment. The primary endpoints were objective response rate (ORR) and disease control rate (DCR). This study included a total of 45 patients. The overall ORR was 33.3% [95% confidence interval (CI),19.0-47.7] and the overall DCR was 57.8% (95% CI, 42.8-72.8). The ORR and DCR were higher in the first-line treatment than those in the second-line treatment (ORR: 45.5% vs. 21.7%, DCR: 63.6% vs. 52.3%). Median progression-free survival in the second-line treatment was 10.5 months (95% CI, 7.9-13.1, P = 0.022). Adverse events occurred in 39 (86.7%) patients. Grade 3/4 adverse reactions occurred in 7 (15.6%) patients. One patient (4.3%) was terminated from treatment due to adverse events. One patient (4.3%) died, which was potentially associated with adverse events. Subgroup analysis indicated that the remission rate in patients with high lymphocyte to monocyte ratio (H-LMR) was higher than that in patients with low lymphocyte to monocyte ratio (L-LMR) (56.25% vs. 25.93%, P = 0.047), and the remission rate in patients with high Prognostic Nutritional Index (H-PNI) was higher than that in patients with low Prognostic Nutritional Index (L-PNI) (66.7% vs. 26.5%, P = 0.046). Camrelizumab combined with apatinib in the treatment of PLC showed encouraging clinical efficacy, with tolerable toxicities. Levels of PNI and LMR may serve as predictors of the prognosis of advanced PLC patients who receive immunotherapy combined with targeted therapy.

Distinct neural networks subserve placebo analgesia and nocebo hyperalgesia.

Neural networks involved in placebo analgesia and nocebo hyperalgesia processes have been widely investigated with neuroimaging methods. However, few studies have directly compared these two processes and it remains unclear whether common or distinct neural circuits are involved. To address this issue, we implemented a coordinate-based meta-analysis and compared neural representations of placebo analgesia (30 studies; 205 foci; 677 subjects) and nocebo hyperalgesia (22 studies; 301 foci; 401 subjects). Contrast analyses confirmed placebo-specific concordance in the right ventral striatum, and nocebo-specific concordance in the dorsal anterior cingulate cortex (dACC), left posterior insula and left parietal operculum during combined pain anticipation and administration stages. Importantly, no overlapping regions were found for these two processes in conjunction analyses, even when the threshold was low. Meta-analytic connectivity modeling (MACM) and resting-state functional connectivity (RSFC) analyses on key regions further confirmed the distinct brain networks underlying placebo analgesia and nocebo hyperalgesia. Together, these findings indicate that the placebo analgesia and nocebo hyperalgesia processes involve distinct neural circuits, which supports the view that the two phenomena may operate via different neuropsychological processes.

Clinical significance of CCNE2 protein and mRNA expression in thyroid cancer tissues.

PURPOSE: Thyroid carcinoma (TC) is the most common endocrinal malignancy worldwide. Cyclin E2 (CCNE2), a member of the cyclin family, acts as a regulatory subunit of cyclin-dependent kinases (CDKs). It controls the transition of quiescent cells into the cell cycle, regulates the G1/S transition, promotes DNA replication, and activates CDK2. This study explored the role and potential molecular mechanisms of CCNE2 expression in TC tissues. MATERIAL/METHODS: Immunohistochemistry was used to evaluate the CCNE2 protein expression levels in TC. High-throughput data on CCNE2 in TC were obtained from RNA sequencing (RNA-seq), microarray, and literature data. The CCNE2 expression levels in TC were comprehensively assessed through an integrated analysis. Analyses of Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPIs) data facilitated the investigation of the relative molecular mechanisms of CCNE2 in TC. RESULTS: The immunohistochemical experiment showed a significant increase in the expression of CCNE2 in the TC tissues. For 505 TC and 59 non-cancerous samples from RNA-seq data, the area under the curve (AUC) was 0.8016 (95% confidence interval [CI] 0.742-0.8612; p<0.001). With another 14 microarrays, the pool standard mean difference [SMD] was 1.01 (95% CI [0.82-1.19]). The pooled SMD of CCNE2 was 1.12 (95% CI [0.60-1.64]), and the AUC was 0.87 (95% CI [0.84-0.90]) for 1157 TC samples and 366 non-cancerous thyroid samples from all possible sources. Nine hub genes were upregulated in TC. CONCLUSIONS: A high expression of CCNE2 may lead to carcinogenesis and the development of TC.

Conscious awareness differentially shapes analgesic and hyperalgesic pain responses.

A large proportion of human cognitive processes may operate outside of conscious awareness. Subliminally presented visual stimuli that are not consciously perceived have a pervasive effect on behavioral and autonomic responses. Recent studies have claimed that placebo/nocebo effects, which are previously thought to require conscious expectancies, can be elicited to comparable levels regardless of whether the stimuli were consciously perceived or not. We systematically explored the role of consciousness in conditioned analgesic and hyperalgesic pain responses using both classical delay conditioning procedure and trace conditioning procedure. In 2 experiments (total N = 247), we found that analgesic and hyperalgesic responses were differentially dependent on the conscious awareness of the relevant stimuli. Specifically, the analgesic response was only significant when stimuli were supraliminal in both conditioning/acquisition phase and test/activation phases. While the hyperalgesic responses were acquired and activated irrespective of stimulus exposure (supraliminal/subliminal), the magnitude of this response was larger when stimuli were supraliminal in the test stage. Our results indicate that analgesic responses require both conscious conditioning and conscious activation, challenging the view that classical conditioning of analgesic pain responses operates without conscious awareness. Hyperalgesic responses are generally not dependent on the consciousness of stimuli, suggesting the presence of a valence-specific rapid regulatory mechanism to enable adaptive responses in threatening circumstances. Our study demonstrates a nascent role of consciousness in the learning of complex cognitive processes. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

The neural correlates of reaching focal points.

In pure-coordination games where there are multiple Nash equilibria, the selection of coordinated responses is inexplicable by rational-choice theory - yet coordination is ubiquitous in daily interactions. The psychological game theory therefore evokes the idea of focal-points: some equilibria being chosen due to its salience, as well as through predicting (i.e., mentalizing) other's response. Previous work has been limited to investigating how structural atrophy relates to deficits in coordination, or how brain activations differ between intuitive and deliberated coordination. In this study, we investigated how the strategy of coordination is reflected in the brain, compared to when no coordination is required. Using functional near-infrared spectroscopy (fNIRS), we examined the neural correlates of deriving a response to a category where participants had to either answer freely (i.e., a survey) or try to match their response with another participant (i.e., coordinate). We found that the coordination trials elicited significantly larger changes in oxyhemoglobin [HbO] concentration than survey trials in frontopolar and lateral prefrontal cortex (PFC). Individual differences in behavioral focal index was significantly correlated with [HbO] concentration in lateral PFC. Granger Causality (GC) analysis revealed greater effective connectivity from frontopolar to lateral PFC, and less GC from lateral PFC to frontopolar in the coordination condition. Our findings highlight the crucial role of frontopolar and lateral PFC in human coordination.

The Effect of Emotion on Prosocial Tendency: The Moderating Effect of Epidemic Severity Under the Outbreak of COVID-19.

During the outbreak of COVID-19, information on the epidemic inundated people's lives and led to negative emotions (e.g., tension, anxiety, and fear) in many people. This study aims to explore the effect of various emotions on prosocial tendencies during the COVID-19 outbreak and the moderating effect of the severity of the epidemic. We explore these effects by conducting a text analysis of the content of posts by 387,730 Weibo users. The results show that the severity of the epidemic promotes prosocial tendencies; anger motivates prosocial tendencies significantly; and the severity of the epidemic moderates the effects of three emotions-anger, sadness, and surprise-on prosocial tendencies. These findings provide a reference for exploring the positive significance of major disasters.

Category-based generalization of placebo and nocebo effects.

Human beings possess the adaptive ability to apply experiential knowledge to new situations. Although this generalization capability has been demonstrated in fear and reward learning, it remains unclear whether it extends to analgesic and hyperalgesic pain responses. Here, we conducted two experiments (total n = 104) to test the generalization effects of placebo analgesia and nocebo hyperalgesia. The first experiment, using a category-based conditioning paradigm in which two categories of images were used as acquisition stimuli, assessed whether pain perception can be generalized to never-seen pictures of the same category in the generalization phase. The second experiment adopted a single stimulus for each category as CS to further examine the generalization effects after learning a single exemplar. Pain ratings showed that participants reported higher pain or lower pain when the pain was preceded by novel stimuli that were conceptually similar to the previously conditioned stimuli, suggesting a generalization of analgesic and hyperalgesic pain modulation effects. These results provide novel evidence that analgesic and hyperalgesic effects on pain perception can be generalized to conceptually similar new items.