Design and application of synthetic 17B-HSD13 substrates reveals preserved catalytic activity of protective human variants.

Several hydroxysteroid dehydrogenase 17-beta 13 variants have previously been identified as protective against metabolic dysfunction-associated steatohepatitis (MASH) fibrosis, ballooning and inflammation, and as such this target holds significant therapeutic potential. However, over 5 years later, the function of 17B-HSD13 remains unknown. Structure-aided design enables the development of potent and selective sulfonamide-based 17B-HSD13 inhibitors.

Quantitative systems toxicology modeling in pharmaceutical research and development: An industry-wide survey and selected case study examples.

Quantitative systems toxicology (QST) models are increasingly being applied for predicting and understanding toxicity liabilities in pharmaceutical research and development. A European Federation of Pharmaceutical Industries and Associations (EFPIA)-wide survey was completed by 15 companies. The results provide insights into the current use of QST models across the industry.

Erratum: [Corrigendum] Relationship between changes in mitochondrial function and hippocampal neuronal apoptosis after recurrent convulsion during developmental stage.

[This corrects the article DOI: 10.3892/etm.2018.

InSAR and machine learning reveal new understanding of coastal subsidence risk in the Yellow River Delta, China.

Coastal subsidence is a geological disaster that has devastating consequences. However, an accurate understanding of its risks involves more than simply assessing the amount or rate of land subsidence. The existing methods used to evaluate geological disaster risks depend on extensive data collection, entail substantial workloads, suffer from error estimation challenges, and lack regional adaptability.

Correlation analysis between plasma fibrinogen and nerve electrophysiological changes in type 2 diabetic peripheral neuropathy.

Introduction: The aim of the study was to investigate the pathogenesis of diabetic peripheral neuropathy (DPN) and the value of fibrinogen (FIB) in the early diagnosis of DPN.

Material And Methods: A total of 121 patients with type 2 diabetes mellitus (T2DM) and DPN hospitalized in the Endocrinology Department of the 923 Hospital of the People's Liberation Army of China were randomly selected between May and October 2020 and divided into a T2DM asymptomatic (no peripheral neuropathy-related symptoms) group (66 cases) and a T2DM symptomatic group (55 cases) according to the presence or absence of clinical neurological symptoms and signs. Forty healthy volunteers were selected as a normal control group.

Role of Fibrinogen in Type-2 Diabetes Mellitus with Diabetic Neuropathy and its Preliminary Mechanism.

Introduction: Diabetic peripheral neuropathy (DN) is the most common complication of type 2 diabetes mellitus (T2DM).

Objective: This study aimed to explore the role of fibrinogen (FIB) in T2DM neuropathy and its preliminary mechanism.

Methods: Ten male Sprague-Dawley rats were divided into a normal control group (NC group) and a T2DM neuropathy model group (DN group).

Triggering and recovery of earthquake accelerated landslides in Central Italy revealed by satellite radar observations.

Earthquake triggered landslides often pose a great threat to human life and property. Emerging research has been devoted to documenting coseismic landslides failed during or shortly after earthquakes, however, the long-term seismic effect that causes unstable landslides only to accelerate, moderately or acutely, without immediate failures is largely neglected. Here we show the activation and recovery of these earthquake accelerated landslides (EALs) in Central Italy, based on satellite radar observations.

Hypoxia inducible factor-1α responds to freezing, anoxia and dehydration stresses in a freeze-tolerant frog.

The wood frog, Rana sylvatica (aka Lithobates sylvaticus) is the main model for studies of natural freeze tolerance among amphibians living in seasonally cold climates. During freezing, ∼65% of total body water can be converted to extracellular ice and this imposes both dehydration and hypoxia/anoxia stresses on cells. The current study analyzed the responses of the alpha subunit of the hypoxia-inducible transcription factor (HIF-1), a crucial oxygen-sensitive regulator of gene expression, to freezing, anoxia or dehydration stresses, examining six tissues of wood frogs (liver, skeletal muscle, brain, heart, kidney, skin).

Relationship of binding-site occupancy, transthyretin stabilisation and disease modification in patients with tafamidis-treated transthyretin amyloid cardiomyopathy.

Background: Tafamidis inhibits progression of transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) by binding TTR tetramer and inhibiting dissociation to monomers capable of denaturation and deposition in cardiac tissue. While the phase 3 ATTR-ACT trial demonstrated the efficacy of tafamidis, the degree to which the approved dose captures the full potential of the mechanism has yet to be assessed.

Methods: We developed a model of dynamic TTR concentrations in plasma to relate TTR occupancy by tafamidis to TTR stabilisation.

Retrospective Study of the Relationship between Variable Benign Epilepsy of Childhood with Centrotemporal Spikes and the Changes of Zinc, MRS, VEEG, and IQ Test.

Benign epilepsy in childhood with centrotemporal spikes (VBECT) has been associated with electroencephalography (EEG), but the relationship of VBECT with zinc, magnetic resonance spectroscopy (MRS), and intelligence quotient (IQ) tests is unclear. The aim of this study was to investigate the association of VBECT with zinc, MRS, EEG, and IQ tests. In this retrospective study, we selected 58 children with variable benign epilepsy with centrotemporal spikes as the experimental group.

Identifying barriers to sustainable apple production: A stakeholder perspective.

Apple is one of the most important cash crops in China. However, negative economic, environmental and social impacts are associated with its production. This study aims to apply a holistic systems perspective to understand existing problems associated with apple production in China and use this information to improve its sustainability.

Elevated Expression of Glycerol-3-Phosphate Phosphatase as a Biomarker of Poor Prognosis and Aggressive Prostate Cancer.

The limitations of the biomarker prostate-specific antigen (PSA) necessitate the pursuit of biomarkers capable of better identifying high-risk prostate cancer (PC) patients in order to improve their therapeutic management and outcomes. Aggressive prostate tumors characteristically exhibit high rates of glycolysis and lipogenesis. Glycerol 3-phosphate phosphatase (G3PP), also known as phosphoglycolate phosphatase (PGP), is a recently identified mammalian enzyme, shown to play a role in the regulation of glucose metabolism, lipogenesis, lipolysis, and cellular nutrient-excess detoxification.

Optimizing Global Navigation Satellite Systems network real-time kinematic infrastructure for homogeneous positioning performance from the perspective of tropospheric effects.

Real-time centimetre-level precise positioning from Global Navigation Satellite Systems (GNSS) is critical for activities including landslide, glacier and coastal erosion monitoring, flood modelling, precision agriculture, intelligent transport systems, autonomous vehicles and the Internet of Things. This may be achieved via the real-time kinematic (RTK) GNSS approach, which uses a single receiver and a network of continuously operating GNSS reference stations (CORS). However, existing CORS networks have often been established simply by attempting regular spacing or in clusters around cities, with little consideration of weather, climate and topography effects, which influence the GNSS tropospheric delay, a substantial GNSS positional error and which prevents homogeneous RTK accuracy attainment.

An EMG-Driven Musculoskeletal Model for Estimating Continuous Wrist Motion.

EMG-based continuous wrist joint motion estimation has been identified as a promising technique with huge potential in assistive robots. Conventional data-driven model-free methods tend to establish the relationship between the EMG signal and wrist motion using machine learning or deep learning techniques, but cannot interpret the functional relationship between neuro-commands and relevant joint motion. In this paper, an EMG-driven musculoskeletal model is proposed to estimate continuous wrist joint motion.

Soluble Low-density Lipoprotein Receptor-related Protein 1 in Juvenile Idiopathic Arthritis.

Objectives: This study aimed to expand knowledge about soluble low-density lipoprotein receptor-related protein 1 (sLRP1) in juvenile idiopathic arthritis (JIA) by determining associations of sLRP1 levels in nonsystemic JIA patients with clinical and inflammatory biomarker indicators of disease activity.

Methods: Plasma sLRP1 and 44 inflammation-related biomarkers were measured at enrollment and 6 months later in a cohort of 96 newly diagnosed Canadian patients with nonsystemic JIA. Relationships between sLRP1 levels and indicators of disease activity and biomarker levels were analyzed at both visits.

Distributed Generalized Nash Equilibrium Seeking and Its Application to Femtocell Networks.

In this article, distributed algorithms are developed to search the generalized Nash equilibrium (NE) with global constraints. Relations between the variational inequality and the NE are investigated via the Karush-Kuhn-Tucker (KKT) optimal conditions, which provide the underlying principle for developing the distributed algorithms. Two time-varying consensus schemes are proposed for each agent to estimate the actions of others, by which a distributed framework is established.

Bearing-Only Formation Control With Prespecified Convergence Time.

This article considers the bearing-only formation control problem, where the control of each agent only relies on relative bearings of their neighbors. A new control law is proposed to achieve target formations in finite time. Different from the existing results, the control law is based on a time-varying scaling gain.

A Physiologically Based Tool to Assess the Risk of Drug-Related Crystalluria.

Drug precipitation in the nephrons of the kidney can cause drug-induced crystal nephropathy (DICN). To aid mitigation of this risk in early drug discovery, we developed a physiologically based model to predict DICN in rats, dogs, and humans. At a minimum, the likelihood of DICN is determined by the level of systemic exposure to the molecule, the molecule's physicochemical properties and the unique physiology of the kidney.

Crop Water Content of Winter Wheat Revealed with Sentinel-1 and Sentinel-2 Imagery.

This study aims to efficiently estimate the crop water content of winter wheat using high spatial and temporal resolution satellite-based imagery. Synthetic-aperture radar (SAR) data collected by the Sentinel-1 satellite and optical imagery from the Sentinel-2 satellite was used to create inversion models for winter wheat crop water content, respectively. In the Sentinel-1 approach, several enhanced radar indices were constructed by Sentinel-1 backscatter coefficient of imagery, and selected the one that was most sensitive to soil water content as the input parameter of a water cloud model.

Automatic Extraction of Water and Shadow from SAR Images Based on a Multi-Resolution Dense Encoder and Decoder Network.

The water and shadow areas in SAR images contain rich information for various applications, which cannot be extracted automatically and precisely at present. To handle this problem, a new framework called Multi-Resolution Dense Encoder and Decoder (MRDED) network is proposed, which integrates Convolutional Neural Network (CNN), Residual Network (ResNet), Dense Convolutional Network (DenseNet), Global Convolutional Network (GCN), and Convolutional Long Short-Term Memory (ConvLSTM). MRDED contains three parts: the Gray Level Gradient Co-occurrence Matrix (GLGCM), the Encoder network, and the Decoder network.

A New Deep Learning Algorithm for SAR Scene Classification Based on Spatial Statistical Modeling and Features Re-Calibration.

Synthetic Aperture Radar (SAR) scene classification is challenging but widely applied, in which deep learning can play a pivotal role because of its hierarchical feature learning ability. In the paper, we propose a new scene classification framework, named Feature Recalibration Network with Multi-scale Spatial Features (FRN-MSF), to achieve high accuracy in SAR-based scene classification. First, a Multi-Scale Omnidirectional Gaussian Derivative Filter (MSOGDF) is constructed.

Theoretical Considerations for Direct Translation of Unbound Liver-to-Plasma Partition Coefficient from In Vitro to In Vivo.

There is considerable interest in developing methods to predict the asymmetric distribution of unbound drug into tissues. The liver is of particular interest due to the multitude of expressed transporters with potential implications for pharmacokinetics, pharmacodynamics, and toxicology. Empirical correlations of in vitro unbound hepatocyte-to-media partition coefficient (in vitro K) and in vivo unbound liver-to-plasma partition coefficient (in vivo K) have been reported without considering the theoretical aspects which might confound the interpretation of such observations.

Modeling Exposure to Understand and Predict Kidney Injury.

Exposure is a critically important aspect to consider in the study and management of drug-induced kidney injury. Although blood concentrations of kidney toxicants often may provide a valid surrogate measure of kidney exposure, the kidney has several unique physiological and biochemical properties that lend themselves to accumulation or exclusion of some drugs at sites of toxicity. In such cases, an understanding of these pharmacokinetic mechanisms can be as important as understanding the underlying mechanisms of toxicity.