PDIA3 orchestrates effector T cell program by serving as a chaperone to facilitate the non-canonical nuclear import of STAT1 and PKM2.

Dysregulated T cell activation underpins the immunopathology of rheumatoid arthritis (RA), yet the machineries that orchestrate T cell effector program remain incompletely understood. Herein, we leveraged bulk and single-cell RNA sequencing data from RA patients and validated protein disulfide isomerase family A member 3 (PDIA3) as a potential therapeutic target. PDIA3 is remarkably upregulated in pathogenic CD4 T cells derived from RA patients and positively correlates with C-reactive protein level and disease activity score 28. Pharmacological inhibition or genetic ablation of PDIA3 alleviates RA-associated articular pathology and autoimmune responses. Mechanistically, T cell receptor signaling triggers intracellular calcium flux to activate NFAT1, a process that is further potentiated by Wnt5a under RA settings. Activated NFAT1 then directly binds to the Pdia3 promoter to enhance the expression of PDIA3, which complexes with STAT1 or PKM2 to facilitate their nuclear import for transcribing T helper 1 (Th1) and Th17 lineage-related genes, respectively. This non-canonical regulatory mechanism likely occurs under pathological conditions, as PDIA3 could only be highly induced following aberrant external stimuli. Together, our data support that targeting PDIA3 is a vital strategy to mitigate autoimmune diseases, such as RA, in clinical settings.

Longitudinal Associations between Metacognition and Spontaneous and Deliberate Mind Wandering During Early Adolescence.

Although metacognition plays a pivotal role in theoretical accounts of mind wandering, their longitudinal relationships have not yet been investigated during the important developmental period of early adolescence. This study aimed to examine the developmental trajectories of spontaneous and deliberate mind wandering and the dynamic associations between metacognition and two types of mind wandering in early adolescence. A sample of 4302 Chinese students beginning in Grade 4 (47.4% female; initial Mage = 9.84, SDage = 0.47) completed questionnaires on five occasions over 2.5 years. The results showed that deliberate mind wandering, but not spontaneous mind wandering, gradually increased from Grade 4 to Grade 6. Metacognition was negatively related to spontaneous mind wandering but positively related to deliberate mind wandering. These findings provide empirical evidence for theoretical viewpoints from both individual differences and developmental perspectives.

Does the reactivity effect of judgments of learning transfer to learning of new information?

ABSTRACTMaking judgments of learning (JOLs) can reactively change memory, a phenomenon termed the reactivity effect. The current study was designed to explore whether the reactivity effect transfers to subsequent learning of new information. Participants studied two blocks of words (Experiment 1) or related word pairs (Experiments 2 & 3). In Block 1, participants in the experimental (JOL) group made a JOL while studying each item, whereas the control (no-JOL) group did not make item-by-item JOLs. Then both groups studied Block 2, in which they did not make JOLs, and finally, they took a test on Blocks 1 and 2. Across Experiments 1 -3, the results showed superior Block 1 test performance in the JOL than in the no-JOL group, demonstrating a positive reactivity effect. Critically, there was minimal difference in Block 2 test performance between the two groups, implying little transfer of the positive reactivity effect to subsequent learning of new information. Furthermore, Experiment 3 demonstrated that the reactivity effect still failed to transfer even when participants explicitly appreciated the benefits of making JOLs. Educational implications are discussed.

Effect of soil water-phosphorus coupling on the photosynthetic capacity of Robinia pseudoacacia L. seedlings in semi-arid areas of the Loess Plateau, China.

Afforestation can improve soil erosion in the ecologically fragile areas of the Loess Plateau; however, the amount of water and phosphorus fertilizer that can promote vegetation survival is unclear, which hinders the improvement of the local ecological environment and the waste of water and fertilizer. In this study, based on field surveys, water and fertilizer control tests on Robinia pseudoacacia L. seedlings in experimental fields, and fitting CO2 response curves to R. pseudoacacia seedlings using a Li-6400 portable photosynthesizer, we measured their leaf nutrient contents and calculated resource use efficiency. The results showed that (1) under the same moisture gradient, except for photosynthetic phosphorus utilization efficiency (PPUE), light use efficiency (LUE), water use efficiency (WUE), carbon utilization efficiency (CUE), and photosynthetic nitrogen use efficiency (PNUE) all increased with increasing phosphorus fertilizer application. Under the same phosphorus fertilizer gradient, WUE increased with decreasing water application, and LUE, CUE, PNUE, and PPUE all reached the maximum at 55-60% of field water holding capacity. (2) Net photosynthetic rate (Pn) of R. pseudoacacia seedlings increased with increasing intercellular carbon dioxide concentration (Ci), and as Ci continued to increase, the increase in Pn became slower, but no maximal electron transport rate (TPU) occurred. Under the same CO2 concentration, Pn reached a maximum at 55-60% of field water holding capacity and phosphorus fertilizer at 30 gPm-2·a-1. (3) Leaf maximum carboxylation rate (Vcmax), maximum electron transport rate (Jmax), daily respiration (Rd), stomatal conductance (Gs), and mesophyll conductance (Gm) reached their maximum at 30 gPm-2·a-1 of phosphorus fertilizer. Vcmax, Jmax, and Rd reached their maximum at 55-60% of field water holding capacity; Gs and Gm reached their maximum at 75-80% of field water holding capacity. (4) The higher the soil phosphorus content, the lower the biochemical (lb), stomatal (ls), and mesophyll (lm). With the increase of soil moisture, lb and ls are higher, and lm is lower. (5) Structural equation modeling showed that water-phosphorus coupling had a less direct effect on Rd and a more direct impact on Gs and Gm. Relative photosynthetic limitation directly affected the photosynthetic rate, indicating that water and phosphorus affected the photosynthetic rate through relative plant limitation. It was concluded that the resource use efficiency and photosynthetic capacity reached the maximum when 55-60% of field water holding capacity was maintained, and phosphorus fertilization was at 30 gP m-2·a-1. Therefore, maintaining suitable soil moisture and phosphorus fertilizer levels in the semi-arid zone of the Loess Plateau can improve the photosynthetic capacity of R. pseudoacacia seedlings.

The interferon regulatory factors, a double-edged sword, in the pathogenesis of type 1 diabetes.

Type 1 diabetes (T1D) is an autoimmune disease resulted from the unrestrained inflammatory attack towards the insulin-producing islet ß cells. Although the exact etiology underlying T1D remains elusive, viral infections, especially those specific strains of enterovirus, are acknowledged as a critical environmental cue involved in the early phase of disease initiation. Viral infections could either directly impede ß cell function, or elicit pathological autoinflammatory reactions for ß cell killing. Autoimmune responses are bolstered by a massive body of virus-derived exogenous pathogen-associated molecular patterns (PAMPs) and the presence of ß cell-derived damage-associated molecular patterns (DAMPs). In particular, the nucleic acid components and the downstream nucleic acid sensing pathways serve as the major effector mechanism. The endogenous retroviral RNA, mitochondrial DNA (mtDNA) and genomic fragments generated by stressed or dying ß cells induce host responses reminiscent of viral infection, a phenomenon termed as viral mimicry during the early stage of T1D development. Given that the interferon regulatory factors (IRFs) are considered as hub transcription factors to modulate immune responses relevant to viral infection, we thus sought to summarize the critical role of IRFs in T1D pathogenesis. We discuss with focus for the impact of IRFs on the sensitivity of ß cells to cytokine stimulation, the vulnerability of ß cells to viral infection/mimicry, and the intensity of immune response. Together, targeting certain IRF members, alone or together with other therapeutics, could be a promising strategy against T1D.

When judging what you know changes what you really know: Soliciting metamemory judgments reactively enhances children's learning.

Recent studies established that making concurrent judgments of learning (JOLs) can significantly alter (typically enhance) memory itself-a reactivity effect. The current study recruited 190 Chinese children (Mage  = 8.68 years; 101 female) in 2020 and 2021 to explore the reactivity effect on children's learning, its developmental trajectory and associated metacognitive awareness. The results showed that making JOLs significantly enhanced retention for students in Grades 1, 3, and 5, with Cohen's ds ranging from 0.40 to 1.33. Grade 5 students exhibited a larger reactivity effect than Grade 1 and 3 students. Children's metacognitive appreciation of the effect was weak. Firsthand experience of the reactivity effect, induced by taking a memory test, enhanced their awareness and calibrated their judgment accuracy.

Soliciting judgments of forgetting reactively enhances memory as well as making judgments of learning: Empirical and meta-analytic tests.

Recent studies found that making judgments of learning (JOLs) can reactively facilitate memory, a phenomenon termed the reactivity effect of JOLs. The current study was designed to explore (1) whether making judgments of forgetting (JOFs) can also enhance memory and (2) whether there is any difference between the reactivity effects of JOFs and JOLs. Experiment 1 found that soliciting JOFs significantly enhanced retention of single words. Experiments 2 and 3 observed minimal difference in reactivity effects between JOFs and JOLs on learning of single words and word pairs. Finally, a meta-analysis was conducted to integrate results across studies to explore whether retention of items studied with JOLs differed from that of items studied with JOFs. The meta-analytic results showed minimal difference. Overall, the documented findings imply that (1) making JOFs reactively enhances memory, and (2) there is little difference in reactivity effects between JOFs and JOLs. These findings support the positive-reactivity theory to account for the reactivity effect.

The role of hydrogen sulphide signalling in macrophage activation.

Hydrogen sulphide (H2 S) is the latest identified small gaseous mediator enabled by its lipophilic nature to freely permeate the biological membranes. Initially, H2 S was recognized by its roles in neuronal activity and vascular relaxation, which makes it an important molecule involved in paracrine signalling pathways. Recently, the immune regulatory function of gasotransmitters, H2 S in particular, is increasingly being appreciated. Endogenous H2 S level has been linked to macrophage activation, polarization and inflammasome formation. Mechanistically, H2 S-induced protein S-sulphydration suppresses several inflammatory pathways including NF-κB and JNK signalling. Moreover, H2 S serves as a potent cellular redox regulator to modulate epigenetic alterations and to promote mitochondrial biogenesis in macrophages. Here in this review, we intend to summarize the recent advancements of H2 S studies in macrophages, and to discuss with focus on the therapeutic potential of H2 S donors by targeting macrophages. The feasibility of H2 S signalling component as a macrophage biomarker under disease conditions would be also discussed.

How cognitive conflict affects judgments of learning: Evaluating the contributions of processing fluency and metamemory beliefs.

Previous research has documented that cognitive conflict affects basic cognitive processes such as memory, reasoning, and attention allocation. However, little research has explored whether its effect can be extended to higher cognitive processes such as metacognitive monitoring. The current study took a novel variant of a Stroop task that employed words presented in a color opposite to the color of the object itself (e.g., heart, presented in green) or same as the color of the object (e.g., forest, presented in green) as targets, an important form of metacognitive monitoring-judgments of learning (JOLs) was used as the measurement index to investigate the influence of cognitive conflict on metacognitive monitoring and to delineate the potential mechanisms underlying the cognitive conflict effect on JOLs. In Experiment 1, results showed that participants gave higher JOLs to consistent than to conflict words, even though cognitive conflict had little influence on memory recall. Experiment 2, employing a self-paced study task, found that conflict words were processed less rapidly than consistent ones, and the difference in processing fluency significantly mediated the cognitive conflict effect on JOLs. Experiment 3 employed an observer-learner task; the mediation analysis showed a complete mediation role of metamemory beliefs (observation JOLs) in the relationship between word type and JOLs. In Experiment 4, research results suggested that participants' beliefs about processing fluency played an important role in the cognitive conflict effect. To conclude, cognitive conflict is a reliable factor affecting higher cognitive processes (metamemory monitoring). Both processing fluency and metamemory beliefs tend to contribute to the cognitive conflict effect.

Florfenicol alleviated lipopolysaccharide (LPS)-induced inflammatory responses in Ctenopharyngodon idella through inhibiting toll / NF-κB signaling pathways.

The present study was conducted to evaluate the anti-inflammatory activity of florfenicol (FFC) against lipopolysaccharide (LPS)-induced inflammatory responses in Ctenopharyngodon idella in vivo and in vitro. Head-kidney (HK) macrophages were pre-treated with 10 µg/mL LPS and then exposed to different concentrations of FFC to determine its in vitro anti-inflammatory activity. Inhibitory effect of FFC on inflammatory mediators TNF-α, IL-6 and IL-1ß, as well as LPS-induced nitric oxide (NO) and prostaglandin E 2 (PGE 2) production were assayed by ELISA. The expression level of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were investigated by RT-PCR. Expression level of TLR-related genes (TLR1, TLR2, TLR4, TLR7, TLR8) expression, tumor necrosis factor receptor-associated factor 6 (TRAF6), transforming growth factor-b-activated kinase 1 (TAK1), Myeloid differentiation factor 88 (MyD88), nucleus p65, NF-κBα (IκBα) were measured by RT-PCR after grass carp were treated with 50, 100 and 200 mg FFC/kg body weight for 3 days. Results from in vitro tests demonstrated that FFC dose-dependently inhibited LPS-induced inflammatory cytokines TNF-α, IL-6 and IL-1ß, inflammatory factors NO and PGE 2 production in macrophages. In addition, iNOS and COX-2 expression levels decreased significantly as compared with LPS treated group. In vivo test demonstrated that treatment with FFC prevented the LPS-induced upregulation of TNF-α, IL-6, IL-1ß, NO and PGE 2. The expression level of iNOS, and COX-2 in FFC-treated grass carp were also downregulated as compared with LPS treated fish. Besides, FFC blocked the expression of Toll-like receptor 2 (TLR2) and then suppressed the phosphorylation of nuclear transcription factor-kappa B (NF-κB) p65 and degradation inhibitor of IκBα. Furthermore, administration of FFC inhibited the up-regulation of IRAK4, TRAF6 and TAK1 induced by LPS. These results suggest that the anti-inflammatory properties of FFC might be the results from the inhibition of iNOS, COX-2, IL-6, IL-1ß, and TNF-α expressions through the down-regulation of Toll/NF-κB signaling pathways.

The anchoring effect in metamemory monitoring.

Judgments about future memory performance (metamemory judgments) are known to be susceptible to illusions and bias. Here we asked whether metamemory judgments are affected, like many other forms of judgment, by numerical anchors. Experiment 1 confirmed previous research showing an effect of informative anchors (e.g., past peer performance) on metamemory monitoring. In four further experiments, we then explored the effects of uninformative anchors. All of the experiments obtained significant anchoring effects on metamemory monitoring; in contrast, the anchors had no effect on recall itself. We also explored the anchoring effect on metamemory control (restudy choices) in Experiment 4. The results suggested that anchors can affect metamemory monitoring, which in turn affects metamemory control. The present research reveals that informative and, more importantly, uninformative numbers that have no influence on recall itself can bias metamemory judgments. On the basis of the current theoretical understanding of the anchoring effect and metamemory monitoring, these results offer insight into the processes that trigger metacognitive biases.

Rare and common species contribute disproportionately to alpine meadow community construction and functional variation.

It is widely accepted that rare species are the first species to become extinct after human-induced disturbances. However, the functional importance of rare species still needs to be better understood, especially in alpine meadow communities with harsher habitats, where the extinction rate of rare species may be higher. This study established a 1.85 × 105 m2 permanent research sample plot on the eastern Tibetan Plateau. We investigated data from 162 plots at 6 different sampling scales in alpine meadows to determine the contribution of rare and common species to alpine meadow communities' structural and functional variability. The results showed that (1) Asteraceae (Compositae) was the dominant family in the surveyed localities. The trends of species diversity indices were the same, and all of them increased with the increase of sampling scale, and the plant community showed apparent scale effects. (2) The community construction of rare species at small scales with high occupancy transitioned from neutral processes to ecological niche processes, while the community construction of common species at different sampling scales was all dominated by ecological niche processes. (3) The trait values of rare species at different sampling scales were different from those of common species, and their distribution in FEs (functional entities) was also different, indicating that they contributed differently to the ecological functions of the communities. Rare species with lower abundance in the surveyed communities had a higher proportion of FEs, indicating that rare species had a more significant proportion of contribution to FEs. The functional redundancy (FR) of rare species was lower than that of common species, and the functional vulnerability (FV) was higher than that of common species. Therefore, the loss of rare species is more likely to cause the loss of community ecological functions, affecting the function and resilience of alpine meadow ecosystems.

Judgments of Learning Reactively Improve Memory by Enhancing Learning Engagement and Inducing Elaborative Processing: Evidence from an EEG Study.

Making judgments of learning (JOLs) can reactively alter memory itself, a phenomenon termed the reactivity effect. The current study recorded electroencephalography (EEG) signals during the encoding phase of a word list learning task to explore the neurocognitive features associated with JOL reactivity. The behavioral results show that making JOLs reactively enhances recognition performance. The EEG results reveal that, compared with not making JOLs, making JOLs increases P200 and LPC amplitudes and decreases alpha and beta power. Additionally, the signals of event-related potentials (ERPs) and event-related desynchronizations (ERDs) partially mediate the reactivity effect. These findings support the enhanced learning engagement theory and the elaborative processing explanation to account for the JOL reactivity effect.

GSK2334470 attenuates high salt-exacerbated rheumatoid arthritis progression by restoring Th17/Treg homeostasis.

High salt (HS) consumption is a risk factor for multiple autoimmune disorders via disturbing immune homeostasis. Nevertheless, the exact mechanisms by which HS exacerbates rheumatoid arthritis (RA) pathogenesis remain poorly defined. Herein, we found that heightened phosphorylation of PDPK1 and SGK1 upon HS exposure attenuated FoxO1 expression to enhance the glycolytic capacity of CD4 T cells, resulting in strengthened Th17 but compromised Treg program. GSK2334470 (GSK), a dual PDPK1/SGK1 inhibitor, effectively mitigated the HS-induced enhancement in glycolytic capacity and the overproduction of IL-17A. Therefore, administration of GSK markedly alleviated HS-exacerbated RA progression in collagen-induced arthritis (CIA) model. Collectively, our data indicate that HS consumption subverts Th17/Treg homeostasis through the PDPK1-SGK1-FoxO1 signaling, while GSK could be a viable drug against RA progression in clinical settings.

Are the contributions of processing experience and prior beliefs to confidence ratings domain-general or domain-specific?

Previous studies on domain generality of metacognition showed inconsistent results about cross-domain correlation of metacognitive resolution, which might result from the varied relationship between actual performance and the information utilized during confidence rating across tasks. The current study investigated metacognitive domain generality using the Bayesian inference model for metamemory (BIM), which suggests that individuals integrate current processing experience and their prior beliefs to construct confidence ratings. Results from three experiments and a series of meta-analyses showed that the correlation between the contribution of processing experience to confidence ratings (parameter Pexp in BIM) across perceptual and memory domains was significantly positive, while the cross-domain correlation of metacognitive resolution (meta-d'/d') was relatively weak. Furthermore, meta-d'/d' was related to specific task requirements, which could lead to very low cross-task correlation of meta-d'/d' even within the same cognitive domain. These results imply that the cross-domain correlation of metacognitive resolution might underestimate metacognitive domain generality, and the cognitive mechanisms underlying confidence rating process itself may be more domain-general. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Decision criteria in signal detection model are not based on the objective likelihood ratio.

How people set decision criteria in signal detection model is an important research question. The likelihood ratio (LR) theory, which is one of the most influential theories about criteria setting, typically assumes that (a) decisions are based on the objective LR of the signal and noise distributions, and (b) LR criteria do not change across tasks with various difficulty levels. However, it is often questioned whether people are really able to know the exact shape of signal and noise distributions, and compute the objective LR accordingly. Here we suggest whether decision criteria are set based on objective LR can be tested in two-condition experiments with different difficulty levels across conditions. We then asked participants in three empirical experiments to perform two-condition perceptual or memory tasks, and give their answer using confidence rating scale. Results revealed that the two assumptions of LR theory contradicted with each other: if we assumed decision criteria were based on objective LR, then the estimated LR criteria differed across difficulty levels, and fanned out as task difficulty decreased. We suggest people might inaccurately estimate the LR in signal detection tasks, and several possible explanations for the distortion of LR are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Individuals with High Metacognitive Ability Are Better at Divergent and Convergent Thinking.

Is metacognitive ability a predictor of creative performance? Previous studies have produced conflicting findings. To clarify whether this relationship exists, the current study used eye tracking techniques and vocal thinking reports to explore creativity differences in individuals with different levels of metacognitive ability. One hundred and twelve participants completed the Metacognitive Ability scale, and were divided into two groups (with thirty participants in each group) based on their metacognition scores (the highest and lowest 27% of metacognitive ability scores). Then, participants in both groups completed two creative thinking tasks (AUT and CCRAT) while their eye behaviors were recorded by eye tracking. The results showed that participants with high metacognitive ability were better at divergent thinking, as evidenced by greater fixation and saccade counts, as well as smaller saccade amplitudes in the AUT task. In addition, Bayesian analyses provide anecdotal evidence that participants with high metacognitive ability tended to be better at convergent thinking. Furthermore, eye tracking results demonstrated that they exhibited longer fixation duration and more fixation count on the materials in the CCRAT task. These findings reflect an important role of metacognition in creative thinking, especially in divergent thinking.

The Relationship between Dispositional Mindfulness and Relative Accuracy of Judgments of Learning: The Moderating Role of Test Anxiety.

Research has demonstrated that metacognition accuracy is far from perfect. The accuracy of judgments of learning (JOLs) is of critical importance in self-regulated learning. To explore what factors constrain JOL accuracy, the current study focused on mindfulness, which is intimately related to metacognition and anxiety. A total of 203 undergraduates (198 valid samples) were recruited to determine the relationships among five dimensions of dispositional mindfulness, test anxiety, and relative accuracy of JOLs. Results revealed that the interaction term for acting with awareness and test anxiety significantly predicted JOL accuracy. Further analyses indicated that for individuals with high test anxiety, but not for those with low test anxiety, acting with awareness positively predicted JOL accuracy. Considering that dispositional mindfulness is modifiable, these results help to inspire researchers to further explore whether mindfulness training can be used as a remedy to improve JOL accuracy.

Do partial and distributed tests enhance new learning?

Testing facilitates subsequent learning of new information, a phenomenon known as the forward testing effect. The effect is often investigated in multilist procedures, where studied lists are followed by a retrieval test, or a control task such as restudying, and learning is compared on the final list. In most studies of the effect, tests include all material from the preceding list. We report four experiments, three of which were preregistered, to determine whether tests that are partial (not including all studied items) and distributed (including retrieval of items from earlier lists) are effective in enhancing new learning. The results show that testing of all studied material is not necessary to produce beneficial effects on new learning or to reduce intrusions. The beneficial effects of testing were substantially mediated by reduced proactive interference. Importantly, there was minimal evidence that the forward learning benefits of partial and distributed tests are offset by a cost to untested items via retrieval-induced forgetting. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Metamemory judgments have dissociable reactivity effects on item and interitem relational memory.

Making metamemory judgments reactively changes item memory itself. Here we report the first investigation of reactive influences of making judgments of learning (JOLs) on interitem relational memory-specifically, temporal (serial) order memory. Experiment 1 found that making JOLs impaired order reconstruction. Experiment 2 observed minimal reactivity on free recall and negative reactivity on temporal clustering. Experiment 3 demonstrated a positive reactivity effect on recognition memory, and Experiment 4 detected dissociable effects of making JOLs on order reconstruction (negative) and forced-choice recognition (positive) by using the same participants and stimuli. Finally, a meta-analysis was conducted to explore reactivity effects on word list learning and to investigate whether test format moderates these effects. The results show a negative reactivity effect on interitem relational memory (order reconstruction), a modest positive effect on free recall, and a medium-to-large positive effect on recognition. Overall, these findings imply that even though making metacognitive judgments facilitates item-specific processing, it disrupts relational processing, supporting the item-order account of the reactivity effect on word list learning. (PsycInfo Database Record (c) 2023 APA, all rights reserved).