Contributions of gains and losses to attentional capture and disengagement: evidence from the gap paradigm.

It is known that movements of visual attention are influenced by features in a scene, such as colors, that are associated with value or with loss. The present study examined the detailed nature of these attentional effects by employing the gap paradigm-a technique that has been used to separately reveal changes in attentional capture and shifting, and changes in attentional disengagement. In four experiments, participants either looked toward or away from stimuli with colors that had been associated either with gains or with losses. We found that participants were faster to look to colors associated with gains and slower to look away from them, revealing effects of gains on both attentional capture and attentional disengagement. On the other hand, participants were both slower to look to features associated with loss, and faster to look away from such features. The pattern of results suggested, however, that the latter finding was not due to more rapid disengagement from loss-associated colors, but instead to more rapid shifting of attention away from such colors. Taken together, the results reveal a complex pattern of effects of gains and losses on the disengagement, capture, and shifting of visual attention, revealing a remarkable flexibility of the attention system.

GNA11 differentially mediates fibroblast growth factor 2- and vascular endothelial growth factor A-induced cellular responses in human fetoplacental endothelial cells.

KEY POINTS: Fetoplacental vascular growth is critical to fetal growth. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) are two major regulators of fetoplacental vascular growth. G protein α subunit 11 (GNA11) transmits signals from many external stimuli to the cellular interior and may mediate endothelial function. It is not known whether GNA11 mediates FGF2- and VEGFA-induced endothelial cell responses under physiological chronic low O2 . In the present study, we show that knockdown of GNA11 significantly decreases FGF2- and VEGFA-induced fetoplacental endothelial cell migration but not proliferation and permeability. Such decreases in endothelial migration are associated with increased phosphorylation of phospholipase C-ß3. The results of the present study suggest differential roles of GNA11 with respect to mediating FGF2- and VEGFA-induced fetoplacental endothelial function. ABSTRACT: During pregnancy, fetoplacental angiogenesis is dramatically increased in association with rapidly elevated blood flow. Any disruption of fetoplacental angiogenesis may lead to pregnancy complications such as intrauterine growth restriction. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) are crucial regulators of fetoplacental angiogenesis. G protein α subunits q (GNAq) and 11 (GNA11) are two members of the Gαq/11 subfamily involved in mediating vascular growth and basal blood pressure. However, little is known about the roles of GNA11 alone with respect to mediating the FGF2- and VEGFA-induced fetoplacental endothelial function. Using a cell model of human umbilical cord vein endothelial cells cultured under physiological chronic low O2 (3% O2 ), we showed that GNA11 small interfering RNA (siRNA) dramatically inhibited (P < 0.05) FGF2- and VEGFA-stimulated fetoplacental endothelial migration (by ∼36% and ∼50%, respectively) but not proliferation and permeability. GNA11 siRNA also elevated (P < 0.05) FGF2- and VEGFA-induced phosphorylation of phospholipase C-ß3 (PLCß3) at S537 in a time-dependent fashion but not mitogen-activated protein kinase 3/1 (ERK1/2) and v-akt murine thymoma viral oncogene homologue 1 (AKT1). These data suggest that GNA11 mediates FGF2- and VEGFA-stimulated fetoplacental endothelial cell migration partially via altering the activation of PLCß3.

Impacts of DRG-Based Prepayment Reform on the Cost and Quality of Patients with Neurologic Disorders: Evidence from a Quasi-Experimental Analysis in Beijing, China.

Purpose: As one of the pioneering pilot cities in China's extensive Diagnosis Related Groups (DRG) -based prepayment reform, Beijing is leading a comprehensive overhaul of the prepayment system, encompassing hospitals of varying affiliations and tiers. This systematic transformation is rooted in extensive patient group data, with the commencement of actual payments on March 15, 2022. This study aims to evaluate the effectiveness of DRG payment reform by examining how it affects the cost, volume, and utilization of care for patients with neurological disorders. Patients and Methods: Utilizing the exogenous shock resulting from the implementation of the DRG-based prepayment system, we adopted the Difference-in-Differences (DID) approach to discern changes in outcome variables among DRG payment cases, in comparison to control cases, both before and following the enactment of the DRG policy. The analytical dataset was derived from patients diagnosed with neurological disorders across all hospitals in Beijing that underwent the DRG-based prepayment reform. Strict data inclusion and exclusion criteria, including reasonableness tests, were applied, defining the pre-reform timeframe as March 15th through October 31st, 2021, and the post-reform timeframe as the corresponding period in 2022. The extensive dataset encompassed 53 hospitals and encompassed hundreds of thousands of cases. Results: The implementation of DRG-based prepayment resulted in a substantial 12.6% decrease in total costs per case and a reduction of 0.96 days in length of stay. Additionally, the reform was correlated with significant reductions in overall in-hospital mortality and readmission rates. Surprisingly, the study unearthed unintended consequences, including a significant reduction in the proportion of inpatient cases classified as surgical patients and the Case Mix Index (CMI), indicating potential strategic adjustments by providers in response to the introduction of DRG payments. Conclusion: The DRG payment reform demonstrates substantial effects in restraining cost escalation and enhancing quality. Nevertheless, caution must be exercised to mitigate potential issues such as patient selection bias and upcoding.

NR2B-containing NMDA receptors promote neural progenitor cell proliferation through CaMKIV/CREB pathway.

Accumulating evidence indicates the involvement of N-methyl-D-aspartate receptors (NMDARs) in regulating neural stem/progenitor cell (NSPC) proliferation. Functional properties of NMDARs can be markedly influenced by incorporating the regulatory subunit NR2B. Here, we aim to analyze the effect of NR2B-containing NMDARs on the proliferation of hippocampal NSPCs and to explore the mechanism responsible for this effect. NSPCs were shown to express NMDAR subunits NR1 and NR2B. The NR2B selective antagonist, Ro 25-6981, prevented the NMDA-induced increase in cell proliferation. Moreover, we demonstrated that the phosphorylation levels of calcium/calmodulin-dependent protein kinase IV (CaMKIV) and cAMP response element binding protein (CREB) were increased by NMDA treatment, whereas Ro 25-6981 decreased them. The role that NR2B-containing NMDARs plays in NSPC proliferation was abolished when CREB phosphorylation was attenuated by CaMKIV silencing. These results suggest that NR2B-containing NMDARs have a positive role in regulating NSPC proliferation, which may be mediated through CaMKIV phosphorylation and subsequent induction of CREB activation.

Cisatracurium inhibits the growth and induces apoptosis of ovarian cancer cells by promoting lincRNA-p21.

As a common muscle relaxant, cisatracurium has shown good antitumor effect on some tumors. Recent studies reported that cisatracurium could inhibit the progression of colon cancer by upregulating tumor suppressor gene p53. However, its role in ovarian cancer and its regulatory effect on p53 and p53 downstream targeting gene long intergenic noncoding RNA p21 (lincRNA-p21) is still unknown. Quantitative Real-time Polymerase Chain Reaction (qRT-PCR) was used to assess the expression of p53, lincRNA-p21 and miR-181b. Cell viability and proliferation were detected by CCK-8 assay and Edu staining, respectively. Wound-healing and Transwell assays were performed to determine the abilities of cell migration and invasion. Apoptosis was evaluated by TUNEL staining. Luciferase reporter assay was conducted to detect the relationship between lincRNA-p21 and miR-181b. As a result, cisatracurium could increase the expressions of p53 and lincRNA-p21 of ovarian cancer cell line (OVCAR-3) in a dose-dependent manner. In addition, cisatracurium significantly inhibited the proliferation, migration and invasion of OVACR-3 cells, and induced apoptosis. However, these above changes in biological function can be attenuated by lincRNA-p21 knockdown. Next, lincRNA-p21 could directly target miR-181b and negatively regulate its expression by luciferase reporter assay. In conclusion, cisatracurium inhibited the progression of OVCAR-3 cells through upregulation of lincRNA-p21 expression activated by p53 inhibiting miR-181b expression. The experimental results provide a new research idea for the application of cisatracurium in ovarian cancer.

Fucoidan inhibits LPS-induced acute lung injury in mice through regulating GSK-3ß-Nrf2 signaling pathway.

The purpose of this study was to investigate the protective effects of fucoidan on Lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. The mice were divided into the control, LPS, and LPS + fucoidan (20, 40, or 80 mg/kg) groups. LPS was given by intracheal instillation and fucoidan was given 1 h before LPS treatment. Myeloperoxidase (MPO) activity, malondialdehyde (MDA), superoxide dismutase (SOD), reactive oxygen species (ROS), glutathione (GSH) contents, and inflammatory cytokine production were detected. The results showed that LPS-induced TNF-α, IL-1ß, and IL-6 production, lung wet/dry (W/D) ratio, ROS, MDA content, and MPO activity were suppressed by fucoidan. The levels of SOD and GSH were increased by fucoidan. Meanwhile, LPS-induced nuclear factor kappa-B (NF-κB) activation was dose-dependently attenuated by fucoidan. Furthermore, fucoidan increased the expression of nuclear factor erythroid-2 related factor 2 (Nrf2), Glycogen synthase kinase3ß (GSK-3ß), and heme oxygenase (HO-1). In vitro, the results demonstrated that fucoidan or GSK-3ß inhibitor significantly inhibited LPS-induced TNF-α production in A549 cells. And the inhibition of fucoidan on TNF-α production was blocked by Nrf2 siRNA. This study showed fucoidan protected mice against LPS-induced ALI through inhibiting inflammatory and oxidative responses via regulating GSK-3ß-Nrf2 signaling pathway.

Elevated NF-κB signaling in Asherman syndrome patients and animal models.

Asherman syndrome (intrauterine adhesion) is often associated with menstrual abnormalities, infertility and recurrent miscarriage in female. Currently the molecular mechanism regulating the pathogenesis of Asherman syndrome is not known. Here we revealed that the inflammatory factor NF-κB expression is significantly elevated in the endometrial samples of Asherman syndrome patients. To further study the molecular mechanisms, we established an Asherman syndrome rat model and confirmed the important role of NF-κB in the pathogenesis of Asherman syndrome. In addition, our rat model provided direct evidence that intrauterine adhesion results in impaired pregnancy, supporting the clinical association between intrauterine adhesion and mis-regulated pregnancy. Our result identified NF-κB as a novel pathogenesis factor of Asherman syndrome and provided new insights for the prevention and treatment of intrauterine adhesions in Asherman syndrome patients.

Inhibition of glutathione metabolism attenuates esophageal cancer progression.

Esophageal squamous cell carcinoma (ESCC) is a deadly malignancy with regard to mortality and prognosis, and the 5-year survival rate for all patients diagnosed with ESCC remains poor. A better understanding of the biological mechanisms of ESCC tumorigenesis and progression is of great importance to improve treatment of this disease. In this study, we demonstrated that the glutathione metabolism pathway is highly enriched in ESCC cells compared with normal esophageal epithelial cells in an in vivo mouse model. In addition, treatment with L-buthionine-sulfoximine (BSO) to deplete glutathione decreased the ESCC tumor burden in mice, thus demonstrating the critical role of glutathione metabolism in ESCC progression. BSO treatment also led to decreased cell proliferation and activation of cell apoptosis in ESCC. Finally, BSO treatment blocked NF-kB pathway activation in ESCC. Our study reveals a new pathway that regulates ESCC progression and suggests that inhibition of glutathione metabolism may be a potential strategy for ESCC treatment.

Jarid2 is essential for the maintenance of tumor initiating cells in bladder cancer.

Bladder cancer is the most common urologic malignancy in China, with an increase of the incidence and mortality rates over past decades. Recent studies suggest that bladder tumors are maintained by a rare fraction of cells with stem cell proprieties. Targeting these bladder tumor initiating cell (TICs) population can overcome the drug-resistance of bladder cancer. However, the molecular and genetic mechanisms regulating TICs in bladder cancer remain poorly defined. Jarid2 is implicated in signaling pathways regulating cancer cell epithelial-mesenchymal transition, and stem cell maintenance. The goal of our study was to examine whether Jarid2 plays a role in the regulation of TICs in bladder cancer. We found that knockdown of Jarid2 was able to inhibit the invasive ability and sphere-forming capacity in bladder cancer cells. Moreover, knockdown of Jarid2 reduced the proportion of TICs and impaired the tumorigenicity of bladder cancer TICs in vivo. Conversely, ectopic overexpression of Jarid2 promoted the invasive ability and sphere-forming capacity in bladder cancer cells. Mechanistically, reduced Jarid2 expression led to the upregulation of p16 and H3K27me3 level at p16 promoter region. Collectively, we provided evidence that Jarid2 via modulation of p16 is a putative novel therapeutic target for treating malignant bladder cancer.