Explore the vast range of titles available.

Post-error slowing (PES) reflects efficient outcome monitoring, manifested as slower reaction time after errors. Cognitive control account assumes that PES depends on error information, whereas orienting account posits that it depends on error frequency. This raises the question how the outcome valence and outcome frequency separably influence the generation of PES. To address this issue, we varied the probability of observation errors (50/50 and 20/80, correct/error) the “partner” committed by employing an observation-execution task and investigated the corresponding behavioral and neural effects. On each trial, participants first viewed the outcome of a flanker-run that was supposedly performed by a ‘partner’ and then performed a flanker-run themselves afterwards. We observed PES in the two error rate conditions. However, electroencephalographic data suggested error-related potentials (oERN and oPe) and rhythmic oscillation associated with attentional process (alpha band) were respectively sensitive to outcome valence and outcome frequency. Importantly, oERN amplitude was positively correlated with PES. Taken together, these findings support the assumption of the cognitive control account, suggesting that outcome valence and outcome frequency are both involved in PES. Moreover, the generation of PES is indexed by oERN, whereas the modulation of PES size could be reflected on the alpha band.

The dynamic recrystallization (DRX) behavior during the thermal deformation process of AZ61 magnesium alloy was systematically studied using a combined finite element (FE) and cellular automaton (CA) model. Isothermal compression experiments on AZ61 magnesium alloy were conducted using a Gleeble-1500 thermal simulator at temperatures ranging from 300 to 450 ℃ and strain rates from 0.003 to 1 s −1 , obtaining true stress–strain curves under various deformation conditions. Based on the obtained experimental data, a high-precision physical constitutive model for AZ61 alloy was established, along with a DRX kinetics model and a recrystallization critical model. At the same time, the grain size model was established by measuring the microstructure of the alloy. In addition, the parameters of the CA model were found, and the dislocation density model for CA simulation was established on this basis. Simulation results indicated that the dynamic recrystallization behavior is influenced by deformation temperature, strain rate, and strain. The predicted DRX volume fraction and average grain size matched well with experimental results, with a maximum error of less than 8%, demonstrating the high accuracy of the established model. This validated the effectiveness and predictive prospect of the CA-FE coupled method, this method provides a powerful tool and theoretical guidance for studying the DRX microstructure evolution of AZ61 magnesium alloy during hot deformation. Graphical Abstract The model and simulation results required for DRX simulation during hot deformation of AZ61 magnesium alloy

Circular RNAs (circRNAs) are covalently closed circular structures without 5′ caps and 3′ tails, which are mainly formed from precursor mRNAs (pre-mRNAs) via back-splicing of exons. With the development of RNA sequencing and bioinformatic analysis, circRNAs were recently rediscovered and found to be widely expressed in the tree of life. Cerebellar degeneration-related protein 1 antisense RNA (CDR1as) is recognized as one of the most well-identified circRNAs. It contains over 70 miR-7 binding sites and can regulate gene activity by sponging miR-7. Increasing numbers of studies have recently demonstrated that CDR1as is abnormally expressed in many types of tumors, such as colorectal cancer, cholangiocarcinoma and osteosarcoma, and plays a vital role in the development of cancer. However, there are few reviews focusing on CDR1as and cancer. Hence, it is important to review and discuss the role of CDR1as in cancer. Here, we first review the main biological features of CDR1as. We then focus on the expression and roles of CDR1as in cancer. Finally, we summarize what is known on the role of CDR1as in cancer and discuss future prospects in this area of research.

Background Abnormally expressed BCR/ABL protein serves as the basis for the development of chronic myeloid leukaemia (CML). The F-actin binding domain (FABD), which is a crucial region of the BCR/ABL fusion protein, is also located at the carboxyl end of the c-ABL protein and regulates the kinase activity of c-ABL. However, the precise function of this domain in BCR/ABL remains uncertain. Methods The FABD-deficient adenovirus vectors Ad-BCR/ABL△FABD, wild-type Ad-BCR/ABL and the control vector Adtrack were constructed, and 32D cells were infected with these adenoviruses separately. The effects of FABD deletion on the proliferation and apoptosis of 32D cells were evaluated by a CCK-8 assay, colony formation assay, flow cytometry and DAPI staining. The levels of phosphorylated BCR/ABL, p73, and their downstream signalling molecules were detected by western blot. The intracellular localization and interaction of BCR/ABL with the cytoskeleton-related protein F-actin were identified by immunofluorescence and co-IP. The effect of FABD deletion on BCR/ABL carcinogenesis in vivo was explored in CML-like mouse models. The degree of leukaemic cell infiltration was observed by Wright‒Giemsa staining and haematoxylin and eosin (HE) staining. Results We report that the loss of FABD weakened the proliferation-promoting ability of BCR/ABL, accompanied by the downregulation of BCR/ABL downstream signals. Moreover, the deletion of FABD resulted in a change in the localization of BCR/ABL from the cytoplasm to the nucleus, accompanied by an increase in cell apoptosis due to the upregulation of p73 and its downstream proapoptotic factors. Furthermore, we discovered that the absence of FABD alleviated leukaemic cell infiltration induced by BCR/ABL in mice. Conclusions These findings reveal that the deletion of FABD diminished the carcinogenic potential of BCR/ABL both in vitro and in vivo. This study provides further insight into the function of the FABD domain in BCR/ABL.

After committing an error, participants tend to perform more slowly. This phenomenon is called post-error slowing (PES). Although previous studies have explored the PES effect in the context of observed errors, the issue as to whether the slowing effect generalizes across tasksets remains unclear. Further, the generation mechanisms of PES following observed errors must be examined. To address the above issues, we employed an observation-execution task in three experiments. During each trial, participants were required to mentally observe the outcomes of their partners in the observation task and then to perform their own key-press according to the mapping rules in the execution task. In Experiment 1, the same tasksets were utilized in the observation task and the execution task, and three error rate conditions (20%, 50% and 80%) were established in the observation task. The results revealed that the PES effect after observed errors was obtained in all three error rate conditions, replicating and extending previous studies. In Experiment 2, distinct stimuli and response rules were utilized in the observation task and the execution task. The result pattern was the same as that in Experiment 1, suggesting that the PES effect after observed errors was a generic adjustment process. In Experiment 3, the response deadline was shortened in the execution task to rule out the ceiling effect, and two error rate conditions (50% and 80%) were established in the observation task. The PES effect after observed errors was still obtained in the 50% and 80% error rate conditions. However, the accuracy in the post-observed error trials was comparable to that in the post-observed correct trials, suggesting that the slowing effect and improved accuracy did not rely on the same underlying mechanism. Current findings indicate that the occurrence of PES after observed errors is not dependent on the probability of observed errors, consistent with the assumption of cognitive control account. Moreover, the PES effect appears across tasksets with distinct stimuli and response rules in the context of observed errors, reflecting a generic process. Additionally, the slowing effect and improved accuracy in the post-observed error trial do not occur together, suggesting that they are independent behavioral adjustments in the context of observed errors.

Background Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) is a subtype of precursor B ALL in genetics and is recognized as a subclass with poor prognosis. Tyrosine kinase inhibitors (TKIs) greatly improve the prognosis of Ph + ALL patients. However, the long-term survival rate is still low (with a 3-year survival rate only 55%). Hence, it is urgent to explore new therapies to improve prognosis for Ph + ALL patients. Protein kinase C (PKC) is proven to be a tumor suppressor in recent years. Activation of PKC by its novel agonist PMA reverts the malignancy of many hematological diseases. However, the effect of PMA on Ph + ALL is unclear. Methods We investigated the biological effects of PMA on Ph + ALL cells and the potential mechanism in this study. In this study, the SUP-B15 and BP190 cell lines were subjected to PMA treatment. Cell proliferation, cycle distribution, apoptosis, protein expression levels, and gene expression changes were assessed using CCK-8 assay, flow cytometry, Western blot analysis, DAPI staining, and quantitative real-time PCR. Additionally, bone marrow mononuclear cells were isolated for further investigation, and RNA sequencing was conducted on SUP-B15 cells. Furthermore, the mouse model was established to evaluate the in vivo biological effects of PMA. Results We found that PMA could promote apoptosis, inhibit proliferation and promote differentiation of human Ph + ALL cells. More importantly, we demonstrated for the first time that these effects caused by PMA were related to the activation of PKC δ and its down-stream molecules, such as p-ERK, p21 and so on. Conclusions PMA exerts an anti-leukemia effect in Ph + ALL by activating PKC δ and its downstream molecules, thereby demonstrating its potential as a therapeutic agent for Ph + ALL.

To evaluate whether low coverage whole genome sequencing is suitable for the detection of malignant pelvic mass and compare its diagnostic value with traditional tumor markers. We enrolled 63 patients with a pelvic mass suspicious for ovarian malignancy. Each patient underwent low coverage whole genome sequencing (LCWGS) and traditional tumor markers test. The pelvic masses were finally confirmed via pathological examination. The copy number variants (CNVs) of whole genome were detected and the Stouffers Z-scores for each CNV was extracted. The risk of malignancy (RM) of each suspicious sample was calculated based on the CNV counts and Z-scores, which was subsequently compared with ovarian cancer markers CA125 and HE4, and the risk of ovarian malignancy algorithm (ROMA). Receiver Operating Characteristic Curve (ROC) were used to access the diagnostic value of variables. As confirmed by pathological diagnosis, 44 (70%) patients with malignancy and 19 patients with benign mass were identified. Our results showed that CA125 and HE4, the CNV, the mean of Z-scores (Zmean), the max of Z-scores (Zmax), the RM and the ROMA were significantly different between patients with malignant and benign masses. The area under curve (AUC) of CA125, HE4, CNV, Zmax, and Zmean was 0.775, 0.866, 0.786, 0.685 and 0.725 respectively. ROMA and RM showed similar AUC (0.876 and 0.837), but differed in sensitivity and specificity. In the validation cohort, the AUC of RM was higher than traditional serum markers. In conclusion, we develop a LCWGS based method for the identification of pelvic mass of suspicious ovarian cancer. LCWGS shows accurate result and could be complementary with the existing diagnostic methods.

Switch costs have been constantly found asymmetrical when switching between two tasks of unequal dominance. We used a combined Stroop-task-switching paradigm and recorded electroencephalographic (EEG) signals to explore the neural mechanism underlying the phenomenon of asymmetrical switch costs. The results revealed that a fronto-central N2 component demonstrated greater negativity in word switch (cW) trials relative to word repeat (wW) trials and both First P3 and P3b components over the parieto-central region exhibited greater positivity in color switch (wC) trials relative to color repeat (cC) trials, whereas a contrasting switch-related fronto-central SP effect was found to have an opposite pattern for each task. Moreover, the time-frequency analysis showed a right-frontal lower alpha band (9-11 Hz) modulation in the word task, whereas a fronto-central upper alpha band (11-13 Hz) modulation was exclusively found in the color task. These results provide evidence for dissociable neural processes, which are related to inhibitory control and endogenous control, contributing to the generation of asymmetrical switch costs.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder characterized by reproductive and metabolic disturbances, which causes a chronic lack of ovulation that leads to increased incidence of atypical endometrial hyperplasia and carcinogenesis. Increasing evidence indicates that metabolic changes may play a crucial role in PCOS pathogenesis; however, the metabolic profile of fluid in PCOS-related endometrium has not yet been characterized. In this study, we successfully constructed three cases of endometrial organoids derived from clinically healthy endometrium. We established a high-androgen model by adding different ratios of estradiol and testosterone to simulate PCOS-like characteristics. Through scanning electron microscopy and immunofluorescence detection, we found that extra androgen treatment-induced cellular damage led to cellular fragments and apoptosis. The intra-organoid fluid (IOF) and extra-organoid fluid (EOF) of the organoids were separated and analyzed by high-throughput quantitative metabolomics. The results showed that amino acid metabolism, specifically glutamine metabolic changes, was the major metabolic pathway altered in the EOF; meanwhile, changes in fatty acids were the main metabolites in the IOF among the groups. Specifically, the in vitro model confirmed that glutamine enhances endometrial stromal cell decidualization with altered mitochondrial function during the implantation process, which may provide the basis for metabolic marker screening and for identifying potential metabolic targets for intervention in female infertility related to PCOS.

Chlamydia trachomatis is an obligate intracellular bacterium that causes multiple diseases involving the eyes, gastrointestinal tract, and genitourinary system. Previous studies have identified that in acute chlamydial infection, C. trachomatis requires Akt pathway phosphorylation and Rab14-positive vesicles to transmit essential lipids from the Golgi apparatus in survival and replication. However, the roles that Akt phosphorylation and Rab14 play in persistent chlamydial infection remain unclear. Here, we discovered that the level of Akt phosphorylation was lower in persistent chlamydial infection, and positively correlated with the effect of activating the development of Chlamydia but did not change the infectivity and 16s rRNA gene expression. Rab14 was found to exert a limited effect on persistent infection. Akt phosphorylation might regulate Chlamydia development and Chlamydia -induced Golgi fragmentation in persistent infection without involving Rab14. Our results provide a new insight regarding the potential of synergistic repressive effects of an Akt inhibitor with antibiotics in the treatment of persistent chlamydial infection induced by penicillin.