Design, synthesis, and biological evaluation of truncated deguelin derivatives as Hsp90 inhibitors

A series of novel B and C-rings truncated deguelin derivatives have been designed and synthesized in the present study as heat shock protein 90 (Hsp90) inhibitors. The synthesized compounds exhibited micromolar antiproliferative potency toward a panel of human cancer cell lines. Their structure-activity relationships (SARs) were investigated in a systematic manner. Compound 21c was identified to have high Hsp90 binding potency (60 nM) and caused degradation of client proteins through ubiquitin proteasome system. Further biological studies showed that compound 21c induced a dose-dependent S and G2-phase cell cycle arrest on human breast cancer MCF-7 cells. Flow cytometry and Western blot analyses confirmed that compound 21c caused apoptosis of MCF-7 cells. In addition, compound 21c showed much potent inhibition on the migration and invasion of MCF-7 cells. Taken together, these results suggest that 21c might be a promising lead compound for further development of Hsp90 inhibitors

Controllable thioester-based hydrogen sulfide slow-releasing donors as cardioprotective agents

Hydrogen sulfide (H2S) is an important signaling molecule with promising protective effects in many physiological and pathological processes. However, the study of H2S has been impeded by the lack of appropriate H2S donors that could mimic its slow-releasing process in vivo. Herein, we report the rational design, synthesis, and biological evaluation of a series of thioester-based H2S donors. These cysteine-activated H2S donors release H2S in a slow and controllable manner. Most of the donors comprising an allyl moiety showed significant cytoprotective effects in H9c2 cellular models of oxidative damage. The most potent donor 5e decreased the mitochondrial membrane potential (MMP) loss and lactate dehydrogenase (LDH) release in H2O2-stimulated H9c2 cells. More importantly, donor 5e exhibited a potent cardioprotective effect in an in vivo myocardial infarction (MI) mouse model by reducing myocardial infarct size and cardiomyocyte apoptosis. Taken together, our studies demonstrated that these new allyl thioesters are potential cardioprotective agents by releasing H2S

A comparative analysis of near-infrared image colorization methods for low-power NVIDIA Jetson embedded systems

The near-infrared (NIR) image obtained by an NIR camera is a grayscale image that is inconsistent with the human visual spectrum. It can be difficult to perceive the details of a scene from an NIR scene; thus, a method is required to convert them to visible images, providing color and texture information. In addition, a camera produces so much video data that it increases the pressure on the cloud server. Image processing can be done on an edge device, but the computing resources of edge devices are limited, and their power consumption constraints need to be considered. Graphics Processing Unit (GPU)-based NVIDIA Jetson embedded systems offer a considerable advantage over Central Processing Unit (CPU)-based embedded devices in inference speed. For this study, we designed an evaluation system that uses image quality, resource occupancy, and energy consumption metrics to verify the performance of different NIR image colorization methods on low-power NVIDIA Jetson embedded systems for practical applications. The performance of 11 image colorization methods on NIR image datasets was tested on three different configurations of NVIDIA Jetson boards. The experimental results indicate that the Pix2Pix method performs best, with a rate of 27 frames per second on the Jetson Xavier NX. This performance is sufficient to meet the requirements of real-time NIR image colorization

Machine Learning for Prediction of Sudden Cardiac Death in Heart Failure Patients With Low Left Ventricular Ejection Fraction: Study Protocol for a Retrospective Multicentre Registry in China

Introduction: Left ventricular ejection fraction (LVEF) ≤35%, as current significant implantable cardioverter-defibrillator (ICD) indication for primary prevention of sudden cardiac death (SCD) in heart failure (HF) patients, has been widely recognised to be inefficient. Improvement of patient selection for low LVEF (≤35%) is needed to optimise deployment of ICD. Most of the existing prediction models are not appropriate to identify ICD candidates at high risk of SCD in HF patients with low LVEF. Compared with traditional statistical analysis, machine learning (ML) can employ computer algorithms to identify patterns in large datasets, analyse rules automatically and build both linear and non-linear models in order to make data-driven predictions. This study is aimed to develop and validate new models using ML to improve the prediction of SCD in HF patients with low LVEF. Methods and analysis: We will conduct a retroprospective, multicentre, observational registry of Chinese HF patients with low LVEF. The HF patients with LVEF ≤35% after optimised medication at least 3 months will be enrolled in this study. The primary endpoints are all-cause death and SCD. The secondary endpoints are malignant arrhythmia, sudden cardiac arrest, cardiopulmonary resuscitation and rehospitalisation due to HF. The baseline demographic, clinical, biological, electrophysiological, social and psychological variables will be collected. Both ML and traditional multivariable Cox proportional hazards regression models will be developed and compared in the prediction of SCD. Moreover, the ML model will be validated in a prospective study. Ethics and dissemination: The study protocol has been approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (2017-SR-06). All results of this study will be published in international peer-reviewed journals and presented at relevant conferences

A Survey of Chinese Pig Farms and Human Healthcare Isolates Reveals Separate Human and Animal Methicillin-Resistant Staphylococcus aureus Populations.

There has been increasing concern that the overuse of antibiotics in livestock farming is contributing to the burden of antimicrobial resistance in people. Farmed animals in Europe and North America, particularly pigs, provide a reservoir for livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA ST398 lineage) found in people. This study is designed to investigate the contribution of MRSA from Chinese pig farms to human infection. A collection of 483 MRSA are isolated from 55 farms and 4 hospitals in central China, a high pig farming density area. CC9 MRSA accounts for 97.2% of all farm isolates, but is not present in hospital isolates. ST398 isolates are found on farms and hospitals, but none of them formed part of the "LA-MRSA ST398 lineage" present in Europe and North America. The hospital ST398 MRSA isolate form a clade that is clearly separate from the farm ST398 isolates. Despite the presence of high levels of MRSA found on Chinese pig farms, the authors find no evidence of them spilling over to the human population. Nevertheless, the ST398 MRSA obtained from hospitals appear to be part of a widely distributed lineage in China. The new animal-adapted ST398 lineage that has emerged in China is of concern

A Review on Computational Trust Models for Multi-agent Systems

Trust plays important roles on effective interaction and cooperation for multi-agent systems(MAS). This study aims at finding out the current situation and future trends of computational trustfor multi-agent systems. Through defining seven common compositional elements for the computational trust models, the study points out significant weaknesses in the current design. Finally, the paper figures out the future research trends through discussion and analysis around the strengths and weaknesses identified. Also the paper proposes an idea of using ontology and XML technologies such as RDF that allow systems to provide both human and machine readable annotations for trust models

Study on variable coefficients singular differential equation via constant coefficients differential equation

Abstract In this paper, we consider the following third-order singular differential equation with variable coefficients: x‴+a(t)x=f(t,x)+e(t). $$x'''+a(t)x=f(t,x)+e(t).$$ By using the Green’s function of the linear differential equation with constant coefficients and some fixed point theorems, i.e., Leray–Schauder alternative principle and Schauder’s fixed point theorem, we prove the existence of positive periodic solutions of the above equation