Patients with basal ganglia damage show preserved learning in an economic game.

Both basal ganglia (BG) and orbitofrontal cortex (OFC) have been widely implicated in social and non-social decision-making. However, unlike OFC damage, BG pathology is not typically associated with disturbances in social functioning. Here we studied the behavior of patients with focal lesions to either BG or OFC in a multi-strategy competitive game known to engage these regions. We find that whereas OFC patients are significantly impaired, BG patients show intact learning in the economic game. By contrast, when information about the strategic context is absent, both cohorts are significantly impaired. Computational modeling further shows a preserved ability in BG patients to learn by anticipating and responding to the behavior of others using the strategic context. These results suggest that apparently divergent findings on BG contribution to social decision-making may instead reflect a model where higher-order learning processes are dissociable from trial-and-error learning, and can be preserved despite BG damage

Multiple tumor suppressors regulate a HIF-dependent negative feedback loop via ISGF3 in human clear cell renal cancer.

Whereas VHL inactivation is a primary event in clear cell renal cell carcinoma (ccRCC), the precise mechanism(s) of how this interacts with the secondary mutations in tumor suppressor genes, including PBRM1, KDM5C/JARID1C, SETD2, and/or BAP1, remains unclear. Gene expression analyses reveal that VHL, PBRM1, or KDM5C share a common regulation of interferon response expression signature. Loss of HIF2α, PBRM1, or KDM5C in VHL-/-cells reduces the expression of interferon stimulated gene factor 3 (ISGF3), a transcription factor that regulates the interferon signature. Moreover, loss of SETD2 or BAP1 also reduces the ISGF3 level. Finally, ISGF3 is strongly tumor-suppressive in a xenograft model as its loss significantly enhances tumor growth. Conversely, reactivation of ISGF3 retards tumor growth by PBRM1-deficient ccRCC cells. Thus after VHL inactivation, HIF induces ISGF3, which is reversed by the loss of secondary tumor suppressors, suggesting that this is a key negative feedback loop in ccRCC. © 2018, Liao et al

Preparation and characterizations of three-dimensional porous collagen/graphene oxide/hydroxyapatite nanocomposite scaffolds for bone tissue engineering

Studies have reported that the incorporation of graphene oxide (GO) and hydroxyapatite (HA) into biocompatible polymers (such as collagen (Col), chitosan, alginate, etc) results in enhanced structural and mechanical properties respectively. The objective of this study was to prepare and characterize three-dimensional (3D) porous Col/GO/HA nanocomposite scaffolds and to investigate cytocompatibility and osteogenic differentiation potential of rat bone marrow mesenchymal stem cells (rBMSCs) on the as-prepared scaffolds. The SEM images revealed that the scaffolds were porous with the pore diameter inversely proportional to the concentration of HA. XRD results were able to depict the characteristic peaks for HA which shows that HA was incorporated into the scaffolds. The rBMSCs which were cultured on the scaffolds were able to attach and proliferate during the 21 days of the experiment which indicates that the as-prepared scaffolds are cytocompatible. The Alizarin red staining demonstrated the presence of calcium deposits as there were orange-red stains on the samples after culturing the cells using the osteogenic differentiation medium. These results demonstrate the promising potential of the 3D porous Col/GO/HA nanocomposite scaffolds for applications in bone tissue engineering

High Thyroid Stimulating Hormone Level Is Associated With Hyperandrogenism in Euthyroid Polycystic Ovary Syndrome (PCOS) Women, Independent of Age, BMI, and Thyroid Autoimmunity: A Cross-Sectional Analysis

Background: Infertility and dyslipidemia are frequently present in both women with polycystic ovary syndrome (PCOS) and subjects with thyroid dysfunction. Limited study regarding the association between thyroid stimulating hormone (TSH) level and phenotypes in euthyroid PCOS women. We aimed to determine whether the variation of TSH level associates with phenotypes in euthyroid PCOS patients.Methods: Cross-sectional study including 600 PCOS and 200 age, body mass index (BMI), and thyroid autoimmunity-matched Chinese women from Renji hospital, Shanghai Jiaotong university during January 2010 and August 2018. The anthropometric and serum biochemical parameters related to TSH, thyroid autoimmunity, lipid profiles, and sex steroids were detected.Results: The TSH level is higher in (2.29 ± 1.24 vs. 1.86 ± 0.90 mu/L, p < 0.001) in PCOS than controls. In euthyroid PCOS patients, TSH, TG, TC, LDL-c, and apoB level increased from non-hyperandrogenism (nonHA) to HA group (all p < 0.05). TSH level is positively associated with TG, apoB, free T, FAI, and negatively associated with apoA (all p < 0.05). The percentage of HA increased from TSH level (57.93% in TSH < = 2.5 group vs. 69.46% in TSH > 2.5 mU/L group, p = 0.006). HA phenotype is increased with TSH level independently of age, BMI, WC, LDL-C. Besides, in multivariate logistic regression analysis TSH and TG significantly associated with HA phenotype.Conclusions: Higher TSH level is associated with increased prevalence of HA phenotype independent of age, BMI and thyroid autoimmunity in euthyroid PCOS

Photocatalytic Inactivation Effect of Gold-Doped TiO2 (Au/TiO2) Nanocomposites on Human Colon Carcinoma LoVo Cells

The photocatalytic inactivation effecting of gold-doped TiO2 (Au/TiO2) nanocomposites on human colon carcinoma LoVo cells was investigated for the first time. The Au/TiO2 samples containing different amounts of Au (1–4 wt%) were prepared by deposition-precipitation (DP) method. These synthesized Au/TiO2 nanocomposites were characterized by transmission electron microscopy (TEM) and inductively coupled plasma atomic emission spectroscopy. It was found that the photocatalytic inactivation effect of TiO2 nanoparticles on LoVo cancer cells could be greatly improved by the surface modification of Au nanoparticles. Furthermore, the loading amount of Au on the surface of TiO2 nanoparticles affects the photocatalytic inactivation efficiency strongly, and it was found that the most efficient nanocomposites were TiO2 nanoparticles doped with 2 wt% Au. When 50 μg/mL 2 wt% Au/TiO2 nanocomposites were used, all of the LoVo cancer cells were killed under the irradiation of UV light (λmax = 365 nm, Intensity = 1.8 mW/cm2) within 100 minutes. But for 50 μg/mL TiO2 nanoparticles, only 40% cancer cells were killed under the same condition

Red list assessments of Chinese higher plants

Based on the two most recent assessments of Chinese higher plants in 2013 and 2020, of 34,450 and 39,330 species, respectively, we analysed the threatened status of Chinese higher plants. In 2020, around 4,088 (10.39%) of the assessed species in China are threatened, 2,875 (7.31%) Near Threatened, 27,593 (70.16%) not currently threatened and categorised as Least Concern and 4,752 (12.08%) categorised as Data Deficient. While in 2013, 3,767 (10.93%) of the assessed higher plants in China are threatened, 2,723 (7.90%) Near Threatened, 24,296 (70.53%) Least Concern and 3,612 (10.48%) Data Deficient. Estimates of the Red List Index in the two years show different patterns when using different weighting methods with the equal steps weighting method showing a slight decrease (0.91675–0.91495) and the extinction risk weighting method showing a slight increase (0.98792–0.98797). We inferred that China’s threatened plant species were likely / relatively effectively protected. However, attention should also be given to the non-threatened species in the future as an additional strategy for their conservation, to maintain their non-threatened status

β-Lapachone Selectively Kills Hepatocellular Carcinoma Cells by Targeting NQO1 to Induce Extensive DNA Damage and PARP1 Hyperactivation

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death globally. Currently there is a lack of tumor-selective and efficacious therapies for hepatocellular carcinoma. β-Lapachone (ARQ761 in clinical form) selectively kill NADPH: quinone oxidoreductase 1 (NQO1)-overexpressing cancer cells. However, the effect of β-Lapachone on HCC is virtually unknown. In this study, we found that relatively high NQO1 and low catalase levels were observed in both clinical specimens collected from HCC patients and HCC tumors from the TCGA database. β-Lapachone treatment induced NQO1-selective killing of HCC cells and caused ROS formation and PARP1 hyperactivation, resulting in a significant decrease in NAD+ and ATP levels and a dramatic increase in double-strand break (DSB) lesions over time in vitro. Administration of β-Lapachone significantly inhibited tumor growth and prolonged survival in a mouse xenograft model in vivo. Our data suggest that NQO1 is an ideal potential biomarker, and relatively high NQO1:CAT ratios in HCC tumors but low ratios in normal tissues offer an optimal therapeutic window to use β-Lapachone. This study provides novel preclinical evidence for β-Lapachone as a new promising chemotherapeutic agent for use in NQO1-positive HCC patients