Prediction of toxicity and identification of key components for complex mixtures containing hormetic components.

Mixtures containing hormetic components are likely to induce hormesis. However, due to the presence of stimulatory effects, predicting the toxicity of such mixtures and identifying their key components face challenges. This study investigated the complex relationship between the stimulatory effects of individual components and their mixtures, focusing on predicting mixture toxicity and identifying key components influencing this toxicity.

Heavy metals in sediments of the river-lake system in the Dianchi basin, China: Their pollution, sources, and risks.

The accumulation of heavy metals in river and lake sediments in basins seriously threatens ecological safety and human health. To manage the basin effectively, it is crucial to understand pollution levels and identify and quantify the sources and risks of heavy metals in rivers and lakes separately for targeted control. In this study, 34 sediment samples were collected from the Dianchi Basin, China, and the pollution, sources, and risks in the river-lake system sediments were systematically analysed for cadmium (Cd), chromium (Cr), arsenic (As), mercury (Hg), lead (Pb), copper (Cu), zinc (Zn), and nickel (Ni).

An innovative mixture sampling strategy with uniform design: Application to global sensitivity analysis of mixture toxicity.

Global sensitivity analysis combined with quantitative high-throughput screening (GSA-qHTS) uses random starting points of the trajectories in mixture design, which may lead to potential contingency and a lack of representativeness. Moreover, a scenario in which all factor levels were at stimulatory effects was not considered, thereby hindering a comprehensive understanding of GSA-qHTS. Accordingly, this study innovatively introduced an optimised experimental design, uniform design (UD), to generate non-random and representative sample points with smaller uniformity deviation as starting points of multiple trajectories.

Liraglutide alleviates high-fat diet-induced kidney injury in mice by regulating the CaMKKβ/AMPK pathway.

Objective: Liraglutide, a glucagon-like peptide-1 receptor agonist, has been shown to regulate blood sugar and control body weight, but its ability to treat obesity-related nephropathy has been poorly studied. Therefore, this study was designed to observe the characteristics and potential mechanism of liraglutide against obesity-related kidney disease.

Methods: Thirty-six C57BL/6J male mice were randomly divided into six groups ( = 6 per group).

Screening for frequently detected quaternary ammonium mixture systems in waters based on frequent itemset mining and prediction of their toxicity.

Screening and prioritizing research on frequently detected mixture systems in the environment is of great significance, as conducting toxicity testing on all mixtures is impractical. Therefore, the frequent itemset mining (FIM) was introduced and applied in this paper to identify variables that commonly co-occur in a dataset. Based on the dataset of the quaternary ammonium compounds (QACs) in the water environment, the four frequent QAC mixture systems with detection rate ≥ 35 % were found, including [BDMM]Cl-[BTMM]Cl (M1), [BDMM]Cl-[BHMM]Cl (M2), [BTMM]Cl -[BHMM]Cl (M3), and [BDMM]Cl-[BTMM]Cl-[BHMM]Cl (M4).

Time-dependent nonmonotonic concentration-response and synergism of alkyl glycosides with different alkyl side chain to Vibrio qinghaiensis sp. -Q67.

Alkyl glycosides (AGs), commonly used nonionic surfactants, may have toxic effects on the environmental organisms. However, the complex concentration-response patterns of AGs with varying alkyl side chains and their mixtures have not been thoroughly studied. Therefore, the luminescence inhibition toxicities of six AGs with different alkyl side chains, namely, ethyl (AG02), butyl (AG04), hexyl (AG06), octyl (AG08), decyl (AG10), and dodecyl (AG12) glucosides, were determined in Vibrio qinghaiensis sp.

Time-dependent hormesis transfer from five high-frequency personal care product components to mixtures.

There is potential for personal care products (PCPs) components and mixtures to induce hormesis. How hormesis is related to time and transmitted from components to mixtures are not clear. In this paper, we conducted determination of components in 16 PCP products and then ran frequent itemset mining on the component data.

Beneficial or harmful: Time-dependent hormesis induced by typical disinfectants and their mixtures with toxicological interaction.

Disinfectants and their mixtures can induce hormesis. However, how the mixture hormesis is related to those of components and the interactions in disinfectant mixtures remain unclear. In this paper, the luminescence inhibition toxicities of chlorinated sodium phosphate (CSP), dodecyl dimethyl benzyl ammonium bromide (DOB), dodecyl dimethyl benzyl ammonium chloride (DOC), ethanol (EtOH), glutaraldehyde (GLA), hydrogen peroxide (HO), isopropyl alcohol (IPA), n-propanol (NPA), and 20 mixture rays in four mixture systems (EtOH-HO, DOB-HO, DOC-EtOH, and EtOH-IPA-NPA) containing at least one component showing hormesis to Vibrio qinghaiensis sp.

A novel mixture sampling strategy combining latin hypercube sampling with optimized one factor at a time method: A case study on mixtures of antibiotics and pesticides.

Global sensitivity analysis in conjunction with quantitative high-throughput screening presents a novel technique for identifying the key components that induce the toxicities of mixtures. However, the mixtures currently designed with this method suffer from unequal frequency sampling, repeated mixtures, and only odd factor levels being considered. Accordingly, we use latin hypercube sampling to generate the starting points of the trajectories to achieve equal frequency sampling and non-repeated mixtures, as well as apply different one factor at a time methods for factors with odd and even levels to achieve suitability for factors with both odd and even levels.

Time-dependent hormetic dose responses of skin care product mixtures to Vibrio qinghaiensis sp.-Q67: Appearance and quantification.

Hormesis is a widely recognized and extensively studied phenomenon. However, few studies have described the quantitative characteristics of hormesis required for appropriate risk assessment. Although skin care product (SCP) mixtures and their active ingredients can induce the hormesis of Vibrio qinghaiensis sp.

Optimized Derivation of Predicted No-Effect Concentrations (PNECs) for Eight Polycyclic Aromatic Hydrocarbons (PAHs) Using HC Based on Acute Toxicity Data.

For persistent organic pollutants, a concern of environmental supervision, predicted no-effect concentrations (PNECs) are often used in ecological risk assessment, which is commonly derived from the hazardous concentration of 5% (HC) of the species sensitivity distribution (SSD). To address the problem of a lack of toxicity data, the objectives of this study are to propose and apply two improvement ideas for SSD application, taking polycyclic aromatic hydrocarbons (PAHs) as an example: whether the chronic PNEC can be derived from the acute SSD curve; whether the PNEC may be calculated by HC to avoid solely statistical extrapolation. In this study, the acute SSD curves for eight PAHs and the chronic SSD curves for three PAHs were constructed.

Environmental exposure and ecological risk of perfluorinated substances (PFASs) in the Shaying River Basin, China.

There have been concerns raised about the environmental effects of perfluoroalkyl substances (PFASs) because of their toxicity, widespread distribution, and persistence. Understanding the occurrences and ecological risk posed by PFASs is essential, especially for the short-chain replacements perfluorobutanoic acid (PFBA) and perfluorobutane sulfonic acid (PFBS), which are now becoming predominant PFASs. The lack of aquatic life criteria (ALC), however, prevents an accurate assessment of the ecological risks of PFBA and PFBS.

Study on the characterization of pesticide modes of action similarity and the multi-endpoint combined toxicity of pesticide mixtures to Caenorhabditis elegans.

With the widespread use of pesticides, the coexistence of multiple low-residue pesticides in environmental media has increased significantly, and the "cocktail" effect caused by this phenomenon has garnered increasing attention. However, owing to the scarcity of information regarding the modes of action (MOAs) of chemicals, the application of concentration addition (CA) models for evaluating and predicting the toxicity of mixture with similar MOAs is limited. Additionally, the joint toxicity laws of complex mixture systems to different toxicity endpoints in organisms remain unclear, and effective methods to test the mixture toxicity on lifespan and reproductive inhibition are lacking.

A novel equal frequency sampling of factor levels (EFSFL) method is applied to identify the dominant factor inducing the combined toxicities of 13 factors.

The research framework combining global sensitivity analysis (GSA) with quantitative high-throughput screening (qHTS), called GSA-qHTS, provides a potentially feasible way to screen for important factors that induce toxicities of complex mixtures. Despite its value, the mixture samples designed using the GSA-qHTS technique still have a shortage of unequal factor levels, which leads to an asymmetry in the importance of elementary effects (EEs). In this study, we developed a novel method for mixture design that enables equal frequency sampling of factor levels (called EFSFL) by optimizing both the trajectory number and the design and expansion of the starting points for the trajectory.

The Application of PiCCO-guided Fluid Resuscitation in Patients With Traumatic Shock.

Background: The aim of this study was to evaluate the application of pulse contour cardiac output (PiCCO) in patients with traumatic shock.

Methods: Seventy-eight patients with traumatic shock were included and grouped. The control group (CG, n = 39) underwent fluid resuscitation through transthoracic echocardiography (TTE) monitoring, and the research group (RG, n = 39) received PiCCO-guided fluid resuscitation.

Deriving the predicted no effect concentrations of 35 pesticides by the QSAR-SSD method.

The widespread use of pesticides results in their frequent detection in water bodies and other environmental media. Pesticide residues may cause certain risks to the environment and human health, and reliable predicted no effect concentrations (PNEC) must be obtained when assessing environmental risks. Species sensitivity distribution (SSD) is an important method for the derivation of chemical PNECs.

New methods of top-to-down mixture toxicity prediction: A case study of eliminating of the effects of cosolvent from binary mixtures.

At present, the toxicity prediction of mixtures mainly focuses on the concentration addition (CA) and independent action (IA) based on individual toxicants to predict the toxicity of multicomponent mixtures. This process of predicting the toxicity of multicomponent mixtures based on single substances or low component mixtures is called down-to-top method in this study. However, due to the particularity of some toxicants, we have to use the top-to-down idea to obtain or eliminate the toxicity of some components from mixtures.

Design, synthesis, biological evaluation and molecular dynamics simulation studies of imidazolidine-2,4-dione derivatives as novel PTP1B inhibitors.

Protein tyrosine phosphatase 1B (PTP1B) is a member of the phosphotyrosine phosphatase family and plays an important role in the signal transduction of diabetes. Inhibition of PTP1B activity can increase insulin sensitivity and reduce blood sugar levels. Therefore, it is urgent to find compounds with novel structures that can inhibit PTP1B.

Exploring Dual Agonists for PPARα/γ Receptors using Pharmacophore Modeling, Docking Analysis and Molecule Dynamics Simulation.

Background: The Peroxisome Proliferator-Activated Receptors (PPARs) are ligandactivated transcription factors belonging to the nuclear receptor family. The roles of PPARα in fatty acid oxidation and PPARγ in adipocyte differentiation and lipid storage have been widely characterized. Compounds with dual PPARα/γ activity have been proposed, combining the benefits of insulin sensitization and lipid lowering into one drug, allowing a single drug to reduce hyperglycemia and hyperlipidemia while preventing the development of cardiovascular complications.

Water quality criteria and ecological risk assessment for ammonia in the Shaying River Basin, China.

Current Chinese surface water environmental quality standard GB3838-2002 for ammonia fails to take water quality factors and native organism distributions in different basins into consideration. In this study, ammonia toxicity tests were performed using three aquatic organisms native to the Shaying River Basin (China). Published ammonia toxicity data with pH and temperature, and toxicity data acquired in this study were used to establish water quality criteria.

The amino acid variants in HLA II molecules explain the major association with adult-onset Still's disease in the Han Chinese population.

Adult-onset Still's disease (AOSD) is a rare autoinflammatory disease with systemic involvement, and its pathophysiology remains unclear. Genome-wide association studies (GWAS) in the Chinese population have revealed an association between AOSD and the major histocompatibility complex (MHC) locus; however, causal variants in the MHC remain undetermined. In the present study, we identified independent amino-acid polymorphisms in human leukocyte antigen (HLA) molecules that are associated with Han Chinese patients with AOSD by fine-mapping the MHC locus.

identification of peroxisome proliferator-activated receptor (PPAR)α/γ agonists from Ligand Expo Components database.

PPARα and PPARγ play important roles in regulating glucose and lipid metabolism. In recent years, the development of dual PPAR agonists has become a hot topic in the field of anti-diabetic medicinal chemistry. The dual PPARα/γ agonists can both improve metabolism and reduce side effects caused by single drugs, and has become a promising strategy for designing effective drugs for the treatment of type 2 diabetes.

Deriving water quality criteria for China for the organophosphorus pesticides dichlorvos and malathion.

Organophosphorus pesticides are effective, cheap, and used extensively but can harm aquatic organism and human health. Here, water quality criteria (WQCs) for dichlorvos (DDVP) and malathion (MAL) were derived. Nine aquatic organisms native to China were used in toxicity tests.