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 A3 (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 (CRP) level and disease activity score 28 (DAS28). Pharmacological inhibition or genetic ablation of PDIA3 alleviates RA-associated articular pathology and autoimmune responses. Mechanistically, T cell receptor (TCR) 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 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.

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.

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 Following Retrieval Practice Produce Minimal Reactivity Effect on Learning of Education-Related Materials.

Testing (i.e., retrieval practice) is one of the most powerful strategies to boost learning. A recent study observed an incidental finding that making judgments of learning (JOLs) following retrieval practice further enhanced learning of education-related texts to a medium extent (Cohen's d = 0.44) by comparison with retrieval practice itself, suggesting that making JOLs may serve as an easy-to-implement educational intervention to improve the benefits of testing. Three experiments (one pre-registered) were conducted to test the replicability of Ariel et al.'s incidental finding and to further determine whether making JOLs following retrieval practice reactively enhances the benefits of testing for text learning. The three experiments consistently provided Bayesian evidence supporting no reactivity effect of JOLs following retrieval practice, regardless of whether the replication experiments were conducted in a laboratory (Experiment 1) or online (Experiments 2 and 3), whether the stimuli were presented in the same language (Experiments 2 and 3) or not (Experiment 1), and whether participants were recruited from the sample pool (Experiment 2) or not (Experiments 1 and 3) as in the original study. These null findings imply that making JOLs cannot be utilized as a practical strategy to enhance the benefits of testing for learning of educationally related materials. Possible explanations for the null reactivity effect of JOLs following retrieval practice are discussed.

Confidence ratings increase response thresholds in decision making.

Many mental processes are reactive - they are altered as a result of introspection and monitoring. It has been documented that soliciting trial-by-trial confidence ratings (CRs) reactively improves decision accuracy and lengthens response times (RTs), but the cognitive mechanisms underlying CR reactivity in decision-making remain unknown. The current study conducted two experiments and employed the drift-diffusion model (DDM) to explore why reporting confidence reactively alters the decision-making process. The results showed that CRs led to enhanced decision accuracy, longer RTs, and higher response thresholds. The findings are consistent with an increased conservatism hypothesis which asserts that soliciting CRs provokes feelings of uncertainty and makes individuals more cautious in their decision making.

CuH-Catalyzed Selective N-Methylation of Amines Using Paraformaldehyde as a C1 Source.

Copper hydride (CuH) complexes have been proposed as key intermediates in synthesis and catalysis. Herein, we developed a highly efficient strategy for CuH-catalyzed N-methylation of aromatic and aliphatic amines using paraformaldehyde and polymethylhydrosiloxane (PMHS) under mild reaction conditions. The reaction proceeded smoothly without additives to furnish the corresponding N-methylated products using cyclic(alkyl)(amino)carbene (CAAC)CuH as a reaction intermediate, which results from a reaction between PMHS and (CAAC)CuCl.

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.

Pancreatic draining lymph nodes (PLNs) serve as a pathogenic hub contributing to the development of type 1 diabetes.

Type 1 diabetes (T1D) is a chronic, progressive autoinflammatory disorder resulting from the breakdown of self-tolerance and unrestrained ß cell-reactive immune response. Activation of immune cells is initiated in islet and amplified in lymphoid tissues, especially those pancreatic draining lymph nodes (PLNs). The knowledge of PLNs as the hub of aberrant immune response is continuously being replenished and renewed. Here we provide a PLN-centered view of T1D pathogenesis and emphasize that PLNs integrate signal inputs from the pancreas, gut, viral infection or peripheral circulation, undergo immune remodeling within the local microenvironment and export effector cell components into pancreas to affect T1D progression. In accordance, we suggest that T1D intervention can be implemented by three major ways: cutting off the signal inputs into PLNs (reduce inflammatory ß cell damage, enhance gut integrity and control pathogenic viral infections), modulating the immune activation status of PLNs and blocking the outputs of PLNs towards pancreatic islets. Given the dynamic and complex nature of T1D etiology, the corresponding intervention strategy is thus required to be comprehensive to ensure optimal therapeutic efficacy.

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.

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.

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).

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.

Comparative analysis of pre- and postmenopausal endometrial cancer in 216 patients.

Background: Endometrial carcinoma (EC) is one of the most common gynecological malignancies and has become more prevalent in recent decades. The clinical manifestations and characteristics of EC in premenopausal and postmenopausal women differ and present with distinct pathological stages and subtypes of EC. Surgery remains the principal therapeutic approach, but the postoperative prognosis is largely affected by the pathological state. Methods: A retrospective study was conducted on 216 patients with EC who were hospitalized from August 2008 to August 2019 in Wuhan Union Hospital. The patients were divided into 2 groups based on the pre- or postmenopausal occurrence of EC. The general clinical characteristics, intraoperative situation, clinicopathological data, and postoperative outcomes of the 2 groups were compared. Results: Patients with premenopausal EC had earlier menarche, a higher incidence of primary infertility and anemia, and fewer pregnancies and deliveries. Patients with postmenopausal EC were older and often had hyperlipidemia and diabetes. Additionally, patients who were postmenopausal had worse tumor pathological gradings, more severe muscular invasion, and a higher rate of lymphatic metastasis. These factors led to a higher demand for postoperative radiotherapy in patients but a lower survival rate. Conclusions: Generally, premenopausal EC differs from postmenopausal EC: the latter is more malignant and has a worse prognosis.

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).

UBC9 deficiency enhances immunostimulatory macrophage activation and subsequent antitumor T cell response in prostate cancer.

The role of tumor-associated macrophages (TAMs), along with the regulatory mechanisms underlying distinct macrophage activation states, remains poorly understood in prostate cancer (PCa). Herein, we report that PCa growth in mice with macrophage-specific Ubc9 deficiency is substantially suppressed compared with that in wild-type littermates, an effect partially ascribed to the augmented CD8+ T cell response. Biochemical and molecular analyses revealed that signal transducer and activator of transcription 4 (STAT4) is a crucial UBC9-mediated SUMOylation target, with lysine residue 350 (K350) as the major modification site. Site-directed mutation of STAT4 (K350R) enhanced its nuclear translocation and stability, thereby facilitating the proinflammatory activation of macrophages. Importantly, administration of the UBC9 inhibitor 2-D08 promoted the antitumor effect of TAMs and increased the expression of PD-1 on CD8+ T cells, supporting a synergistic antitumor efficacy once it combined with the immune checkpoint blockade therapy. Together, our results demonstrate that ablation of UBC9 could reverse the immunosuppressive phenotype of TAMs by promoting STAT4-mediated macrophage activation and macrophage-CD8+ T cell crosstalk, which provides valuable insights to halt the pathogenic process of tumorigenesis.

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).

SUMOylation of ERp44 enhances Ero1α ER retention contributing to the pathogenesis of obesity and insulin resistance.

OBJECTIVE: As the only E2 conjugating enzyme for the SUMO system, Ubc9-mediated SUMOylation has been recognized to regulate diverse biological processes, but its impact on adipocytes relevant to obesity and insulin resistance is yet to be elucidated. METHODS: We established adipocyte-specific Ubc9 deficient mice to explore the effects of Ubc9 on obesity and metabolic disorders induced by high-fat diet (HFD) in adult mice. The molecular targets of SUMOylation were explored by liquid chromatography-mass spectrometry, and the regulatory mechanism of SUMOylation in T2D was analyzed. RESULTS: Adipocyte-specific depletion of Ubc9 (AdipoQ-Cre-Ubc9fl/fl, Ubc9AKO) protected mice from HFD-induced obesity, insulin resistance, and hepatosteatosis. The Ubc9AKO mice were featured by the reduced HFD-induced endoplasmic reticulum (ER) stress and inflammatory response. Mechanically, over nutrition rendered adipocytes to undergo a SUMOylation turnover characterized by the change of SUMOylation levels and substrates. ERp44 displayed the highest change in terms of SUMOylation levels of substrates involved in ER-related functions. The lack of ERp44 SUMOylation at lysine 76 (K76) located within the thioredoxin (TRX)-like domain by Ubc9 deficiency enhanced its degradation and suppressed its covalent binding to Ero1α, an oxidase that exists in the ER but lacks ER retention motif, thereby alleviating endoplasmic reticulum stress by promoting Ero1α secretion. CONCLUSIONS: Our data suggest that modulation of ERp44 SUMOylation in adipocytes could be a feasible strategy against obesity and insulin resistance in clinical settings.

Judgments of learning reactively facilitate visual memory by enhancing learning engagement.

Recent studies have found that making judgments of learning (JOLs) for verbal materials changes memory itself, a form of reactivity effect on memory. The current study explores the reactivity effect on visual (image) memory and tests the potential role of enhanced learning engagement in this effect. Experiment 1 employed object image pairs as stimuli and observed a positive reactivity effect on memory for visual details. Experiment 2 conceptually replicated this positive reactivity effect using pairs of scene images. Experiment 3 introduced mind wandering (MW) probes to measure participants' attentional state (learning engagement) and observed that making JOLs significantly reduced MW. More importantly, reduced MW mediated the reactivity effect. Lastly, Experiment 4 found that a manipulation that heightened learning motivation decreased the reactivity effect. Overall, the current study provides the first demonstration of the reactivity effect on visual memory, as well as support for the enhanced learning engagement explanation. Practical implications are discussed.

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).