Do the government subsidies inhibit the entity over-financialization? Fresh evidence from China

In order to verify effect of the industrial policies on solving the problem of market failure, we collect the data from China A-share listed companies among 2008-2019, and analyze the effect of government subsidies on the entity over-financialization. The results show that government subsidies significantly inhibit the entity over-financialization. Because the government subsidies could increase the performance of enterprise’s main business and level of the enterprise’s profitability. Subsequently, the enterprise’s arbitrage from cross-industries and the managers’ composition could be decreased. Consequently, government subsidies could reduce the entity over-financialization by the reduce of enterprise’s arbitrage from multi-industries and increase of the managers’ composition which is related to the enterprise’s performance. The results also indicate that the entity financialization is mainly motivated by enterprise arbitrage rather than ‘preventive reserve’ in China. Moreover, the inhibitory effect of government subsidies on the entity over-financialization is only significant in the enterprises with non-state-owned, high-tech, and higher level of demand of innovation. Thus, the government should accurately implement subsidy policies for the enterprises and increase the supports for enterprises with high-tech and higher level of demand of innovation, which could promote economy high-quality development

HOXC8 regulates self-renewal, differentiation and transformation of breast cancer stem cells

Background: Homeobox genes are master regulators of cell fate during embryonic development and their expression is altered in cancer. By regulating the balance between cell proliferation and differentiation, they maintain homeostasis of normal tissues. Here, we screened the expression of homeobox genes in mammary stem cells to establish their role in stem cells transformation in breast cancer. Methods: Using a Homeobox Genes PCR array, we screened 83 homeobox genes in normal cancer breast stem/progenitor cells isolated by flow cytometry. The candidate gene HOXC8 epigenetic regulation was studied by DNA methylation and miRNA expression analyses. Self-renewal and differentiation of HOXC8-overexpressing or knockdown cells were assessed by flow cytometry and mammosphere, 3D matrigel and soft agar assays. Clinical relevance of in vitro findings were validated by bioinformatics analysis of patient datasets from TCGA and METABRIC studies. Results: In this study we demonstrate altered expression of homeobox genes in breast cancer stem/progenitor cells. HOXC8 was consistently downregulated in stem/progenitor cells of all breast molecular subtypes, thus representing an interesting tumour suppressor candidate. We show that downregulated expression of HOXC8 is associated with DNA methylation at the gene promoter and expression of miR196 family members. Functional studies demonstrated that HOXC8 gain of function induces a decrease in the CD44+/CD24-/low cancer stem cell population and proportion of chemoresistant cells, with a concomitant increase in CD24+ differentiated cells. Increased HOXC8 levels also decrease the ability of cancer cells to form mammospheres and to grow in anchorage-independent conditions. Furthermore, loss of HOXC8 in non-tumorigenic mammary epithelial cells expands the cancer stem/progenitor cells pool, increases stem cell self-renewal, prevents differentiation induced by retinoic acid and induces a transformed phenotype. Conclusions: Taken together, our study points to an important role of homeobox genes in breast cancer stem/progenitor cell function and establishes HOXC8 as a suppressor of stemness and transformation in the mammary gland lineag

Development of a potent DOTA-conjugated bombesin antagonist for targeting GRPr-positive tumours

Purpose: Radiolabelled somatostatin-based antagonists show a higher uptake in tumour-bearing mouse models than agonists of similar or even distinctly higher receptor affinity. Very similar results were obtained with another family of G protein-coupled receptor ligands, the bombesin family. We describe a new conjugate, RM2, with the chelator DOTA coupled to D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 via the cationic spacer 4-amino-1-carboxymethyl-piperidine for labelling with radiometals such as 111In and 68Ga. Methods: RM2 was synthesized on a solid support and evaluated in vitro in PC-3 cells. IC50 and Kd values were determined. The antagonist potency was evaluated by immunofluorescence-based internalization and Ca2+ mobilization assays. Biodistribution studies were performed in PC-3 and LNCaP tumour-bearing mice with 111In-RM2 and 68Ga-RM2, respectively. PET/CT studies were performed on PC-3 and LNCaP tumour-bearing nude mice with 68Ga-RM2. Results: RM2 and 111In-RM2 are high-affinity and selective ligands for the GRP receptor (7.7±3.3nmol/l for RM2; 9.3±3.3nmol/l for natIn-RM2). The potent antagonistic properties were confirmed by an immunofluorescence-based internalization and Ca2+ mobilization assays. 68Ga- and 111In-RM2 showed high and specific uptake in both the tumour and the pancreas. Uptake in the tumour remained high (15.2±4.8%IA/g at 1h; 11.7±2.4%IA/g at 4h), whereas a relatively fast washout from the pancreas and the other abdominal organs was observed. Uptake in the pancreas decreased rapidly from 22.6±4.7%IA/g at 1h to 1.5±0.5%IA/g at 4h. Conclusion: RM2 was shown to be a potent GRPr antagonist. Pharmacokinetics and imaging studies indicate that 111In-RM2 and 68Ga-RM2 are ideal candidates for clinical SPECT and PET studie

LLM Attributor: Interactive Visual Attribution for LLM Generation

While large language models (LLMs) have shown remarkable capability to generate convincing text across diverse domains, concerns around its potential risks have highlighted the importance of understanding the rationale behind text generation. We present LLM Attributor, a Python library that provides interactive visualizations for training data attribution of an LLM's text generation. Our library offers a new way to quickly attribute an LLM's text generation to training data points to inspect model behaviors, enhance its trustworthiness, and compare model-generated text with user-provided text. We describe the visual and interactive design of our tool and highlight usage scenarios for LLaMA2 models fine-tuned with two different datasets: online articles about recent disasters and finance-related question-answer pairs. Thanks to LLM Attributor's broad support for computational notebooks, users can easily integrate it into their workflow to interactively visualize attributions of their models. For easier access and extensibility, we open-source LLM Attributor at https://github.com/poloclub/ LLM-Attribution. The video demo is available at https://youtu.be/mIG2MDQKQxM.Comment: 8 pages, 3 figures, For a video demo, see https://youtu.be/mIG2MDQKQx

BAP1 dependent expression of long non-coding RNA NEAT-1 contributes to sensitivity to gemcitabine in cholangiocarcinoma

Expression of NEAT-1 in malignant cholangiocytes. (PDF 11 kb

A finite strain nonlinear human mitral valve model with fluid structure interaction

A simulated human mitral valve under a physiological pressure loading is developed using a hybrid finite element immersed boundary method, which incorporates experimentally based constitutive laws in a three-dimensional fluid-structure interaction framework. A transversely isotropic material constitutive model is used for characterizing the mechanical behaviour of the mitral valve tissue based on recent mechanical tests of healthy human mitral leaflets. Our results show good agreement, in terms of the flow rate and the closing and opening configurations, with the measurements from the magnetic resonance images. The stresses in the anterior leaflet are found to be higher than those in the posterior leaflet, and concentrated around the annulus trigons and free edges of the valve leaflets. Those areas are located where the leaflet has the highest curvature. Effects of the chordae tendineae in the material model are studied and the results show that these chordae play an important role in providing a secondary orifice for the flow when valve opens. Although there are some discrepancies to be overcome in future works, our simulations show that the developed computational model is promising in mimicking the in vivo mitral valve dynamics and providing important information that are not obtainable by in vivo measurements. This article is protected by copyright. All rights reserved

Neo-LVOT and Transcatheter Mitral Valve Replacement: Expert Recommendations

With the advent of transcatheter mitral valve replacement (TMVR), the concept of the neo-left ventricular outflow tract (LVOT) was introduced and remains an essential component of treatment planning. This paper describes the LVOT anatomy and provides a step-by-step computed tomography methodology to segment and measure the neo-LVOT while discussing the current evidence and outstanding challenges. It also discusses the technical and hemodynamic factors that play a major role in assessing the neo-LVOT. A summary of expert-based recommendations about the overall risk of LVOT obstruction in different scenarios is presented along with the currently available methods to reduce the risk of LVOT obstruction and other post-procedural complications

Optical Coherence Tomography Angiography of Optic Disc Perfusion in Glaucoma

Purpose To compare optic disc perfusion between normal subjects and subjects with glaucoma using optical coherence tomography (OCT) angiography and to detect optic disc perfusion changes in glaucoma. Design Observational, cross-sectional study. Participants Twenty-four normal subjects and 11 patients with glaucoma were included. Methods One eye of each subject was scanned by a high-speed 1050-nm–wavelength swept-source OCT instrument. The split-spectrum amplitude-decorrelation angiography (SSADA) algorithm was used to compute 3-dimensional optic disc angiography. A disc flow index was computed from 4 registered scans. Confocal scanning laser ophthalmoscopy (cSLO) was used to measure disc rim area, and stereo photography was used to evaluate cup/disc (C/D) ratios. Wide-field OCT scans over the discs were used to measure retinal nerve fiber layer (NFL) thickness. Main Outcome Measures Variability was assessed by coefficient of variation (CV). Diagnostic accuracy was assessed by sensitivity and specificity. Comparisons between glaucoma and normal groups were analyzed by Wilcoxon rank-sum test. Correlations among disc flow index, structural assessments, and visual field (VF) parameters were assessed by linear regression. Results In normal discs, a dense microvascular network was visible on OCT angiography. This network was visibly attenuated in subjects with glaucoma. The intra-visit repeatability, inter-visit reproducibility, and normal population variability of the optic disc flow index were 1.2%, 4.2%, and 5.0% CV, respectively. The disc flow index was reduced by 25% in the glaucoma group (P = 0.003). Sensitivity and specificity were both 100% using an optimized cutoff. The flow index was highly correlated with VF pattern standard deviation (R[superscript 2] = 0.752, P = 0.001). These correlations were significant even after accounting for age, C/D area ratio, NFL, and rim area. Conclusions Optical coherence tomography angiography, generated by the new SSADA, repeatably measures optic disc perfusion and may be useful in the evaluation of glaucoma and glaucoma progression.National Institutes of Health (U.S.) (Grant 1R01 EY023285-01)Rosenbaum's P30EY010572National Institutes of Health (U.S.). Clinical and Translational Science Awards (CTSA) Program (Grant UL1TR000128)Research to Prevent Blindness, Inc. (United States) (Grant R01-EY11289-26)United States. Air Force Office of Scientific Research (FA9550-10-1-0551)German Research Foundation (DFG-HO-1791/11-1)German Research Foundation (DFG-GSC80-SAOT)German Research Foundation (Training Group 1773

Antihyperglycemic Effect of Ganoderma Lucidum Polysaccharides on Streptozotocin-Induced Diabetic Mice

The current study evaluated the glucose-lowering effect of ganoderma lucidum polysaccharides (Gl-PS) in streptozotocin (STZ)-induced diabetic mice. The diabetic mice were randomly divided into four groups (8 mice per group): diabetic control group, low-dose Gl-PS treated group (50 mg/kg, Gl-PS), high-dose Gl-PS treated group (150 mg/kg, Gl-PS) and positive drug control treated group (glibenclamide, 4 mg/kg), with normal mice used as the control group. Body weights, fasting blood glucose (FBG), serum insulin and blood lipid levels of mice were measured. After 28 days of treatment with Gl-PS, body weights and serum insulin levels of the Gl-PS treated groups was significantly higher than that of the diabetic control group, whereas FBG levels was significantly lower. Moreover, total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) levels of the Gl-PS treated groups had dropped, whereas the high density lipoprotein cholesterol (HDL-C) levels had increased. In addition, according to acute toxicity studies, Gl-PS did not cause behavioral changes and any death of mice. These data suggest that Gl-PS has an antihyperglycemic effect. Furthermore, considering the Gl-PS effects on lipid profile, it may be a potential hypolipidaemic agent, which will be a great advantage in treating diabetic conditions associated with atherosclerosis or hyperlipidemia