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Beta-cypermethrin (β-CYP) consists of four chiral isomers, acting as an environmental estrogen and causing reproductive toxicity, neurotoxicity, and dysfunctions in multiple organ systems. This study investigated the toxic effects of β-CYP, its isomers, metabolite 3-phenoxybenzoic acid (3-PBA), and 17β-estradiol (E2) on HTR-8/SVneo cells. We focused on the toxic mechanisms of β-CYP and its specific isomers. Our results showed that β-CYP and its isomers inhibit HTR-8/SVneo cell proliferation similarly to E2, with 100 μM 1S-trans-αR displaying significant toxicity after 48 h. Notably, 1S-trans-αR, 1R-trans-αS, and β-CYP were more potent in inducing apoptosis and cell cycle arrest than 1R-cis-αS and 1S-cis-αR at 48 h. AO/EB staining and flow cytometry indicated dose-dependent apoptosis in HTR-8/SVneo cells, particularly at 100 μM 1R-trans-αS. Scratch assays revealed that β-CYP and its isomers variably reduced cell migration. Receptor inhibition assays demonstrated that post-ICI 182780 treatment, which inhibits estrogen receptor α (ERα) or estrogen receptor β (ERβ), β-CYP, its isomers, and E2 reduced HTR-8/SVneo cell viability, whereas milrinone, a phosphodiesterase 3 A (PDE3A) inhibitor, increased viability. Molecular docking studies indicated a higher affinity of β-CYP, its isomers, and E2 for PDE3A than for ERα or ERβ. Consequently, β-CYP, its isomers, and E2 consistently led to decreased cell viability. Transcriptomics and RT-qPCR analyses showed differential expression in treated cells: up-regulation of Il24 and Ptgs2 , and down-regulation of Myo7a and Pdgfrb , suggesting the PI3K-AKT signaling pathway as a potential route for toxicity. This study aims to provide a comprehensive evaluation of the cytotoxicity of chiral pesticides and their mechanisms. [Display omitted] • 1S-trans-αR, 1R-trans-αS cause higher apoptosis in HTR-8/SVneo cells. • The isoforms of β-CYP show varied effects on cell migration and cycle. • β-CYP binds to PDE3A more than ER receptors, affecting cell viability. • 1R-trans-αS and 1S-trans-αR more potent than β-CYP in cellular impact. [ABSTRACT FROM AUTHOR]

The role of plant composition should be considered during ecological risk assessment of soil petroleum contamination. To evaluate the influences of plant composition on phytotoxicity, petroleum degraders, and petroleum degradation, four treatments were arranged in the present study: unplanted, bristle grass only, alfalfa only, and bristle grass and alfalfa mixed planted in uncontaminated soil or petroleum contaminated soil (w/w, 1.0%). Petroleum contamination inhibited the growth of bristle grass and alfalfa significantly, and alfalfa growth inhibition was significantly alleviated when mixed planted with bristle grass ( p  < 0.05). MPN analysis indicated that the mixed plant treatment can gather the benefits of two species, and facilitate the development of alkane, total hydrocarbon and PAH degraders in contaminated soil, but not occur in uncontaminated soil. Compared with alfalfa only treatment, the degradation rates for total petroleum hydrocarbons (TPH) and aliphatic fraction were significantly increased in the mixed plant treatment ( p  < 0.05). However, the degradation of aromatic petroleum fraction was not received substantial improvement in the mixed plant treatment, despite containing an abundant PAH degraders. Overall, mixed plant cultivation had the significant influences on plant growth, microbial community and petroleum degradation in contaminated soils. The study provides valuable insights for vegetation restoration and remediation systems in petroleum contaminated sites of study area. [ABSTRACT FROM AUTHOR]

This paper mainly focuses on designing a distributed observer-based controller for a flexible-link manipulator bonded with piezoelectric actuators. The dynamic model of the link can be taken as an Euler–Bernoulli beam and takes on the form of partial differential equations (PDEs). The proposed observer, which is proven exponentially stable, has the ability to estimate infinite dimensional states, and only the boundary practical measurement values are needed. A novel distributed observer-based controller is subsequently developed to make the joint position track a desired trajectory and rapidly regulate vibrations on the whole beam, which is the main contribution of the paper. The closed-loop system is guaranteed exponentially stable by theoretical analysis and its favorable performance is demonstrated by numerical simulations. [ABSTRACT FROM AUTHOR]

This paper focuses on designing an observer for a flexible-link manipulator based on the partial differential equation (PDE) dynamic model. The main contribution of this observer׳s novel design is its ability to estimate vibratory, infinite dimensional states requiring only the practical measurement values of boundary positions. The proposed observer is proven asymptotically stable by theoretical analysis. The vibration of the flexible link is eliminated with a PD control. Favorable performance of the closed-loop system is demonstrated by simulations. [ABSTRACT FROM AUTHOR]

Abstract: The location template matching (LTM) method is occasionally used in the area of structural health monitoring and human–computer interface system when the location of impact on an object is needed to be identified. In general, the LTM method utilizes the cross-correlation (or the correlation coefficient) between two time signals, and its performance is influenced by many factors such as the spatial resolution of the pre-defined reference points, the frequency bandwidth of a signal and the length of data, etc. In addition, the correlation based LTM method often needs many sensors to improve the accuracy of identification. To overcome these disadvantages, a group delay based LTM method (namely G-LTM) is introduced in this paper. Particularly, the proposed method uses the group delay of a fictitious linear time-invariant system as a measure of similarity. The experimental results verify a high quality of the G-LTM method by maintaining 100% accuracy for all the different grid spacing while the accuracy of the correlation based LTM method decreases significantly as the grid spacing becomes smaller. [Copyright &y& Elsevier]

The increased production and environmental release of graphene nanoparticles has raised concerns about its environmental impact, but the effects of graphene on living organisms at the metabolic level remain unknown. In this study, we used matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI)-based untargeted metabolomics to investigate the metabolic response of juvenile earthworms (Eisenia fetida) to graphene exposure in soil tests for the first time. Our results reveal that graphene-exposure significantly disturbs earthworm metabolome, and graphene toxicity on earthworm shows non-concentration-dependent effect. Alanine, phenylalanine, proline, glutamate, arginine, histidine, maltose, glucose, malate, succinate, myo-inositol, and spermidine were successfully screened as significantly change compounds in earthworms for the exposure of graphene. The heterogeneous distributions of these metabolites in earthworm were also clearly imaged by MALDI-MSI. Our MSI results fully showed that the metabolite expression levels in juvenile earthworms significantly changed (up-/down-regulation) after exposure to graphene nanoparticles. This work improves our understanding of graphene nanoparticle toxicity to juvenile earthworms and also enables the continued progression of MALDI-MSI-based metabolomics as an emerging, reliable, and rapid ecotoxicological tool for assessing contaminant toxicity. • The effects of graphene on earthworm metabolites were studied for the first time. • MALDI-MS in-situ detection shows metabolic change in earthworm exposed to graphene. • Graphene exposure disturbs the metabolic balance of the earthworms. • MALDI-MSI is a promising ecotoxicological tool for assessing contaminant toxicity. [ABSTRACT FROM AUTHOR]

Biocontrol microbes are environment-friendly and safe for humans and animals. To seek biocontrol microbes effective in suppressing tomato gray mold is important for tomato production. Therefore, serial experiments were conducted to characterize the antagonism of Bacillus velezensis HY19, a novel self-isolated biocontrol bacterium, against Botrytis cinerea in vitro and the control on tomato gray mold in greenhouse. This bacterium produced extracellular phosphatase, protease, cellulose and siderophores, and considerably inhibited the growth of B. cinerea. A liquid chromatography-mass spectrometry (LC-MS) detected salicylic acid and numerous antifungal substances present in B. velezensis HY19 fermentation liquid (BVFL). When B. cinerea was grown on potato glucose agar, BVFL crude extract remarkably suppressed the fungal growth and reduced protein content and the activities of catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD). Transcriptome studies showed that BVFL crude extract significantly induced different expression of numerous genes in B. cinerea , most of which were down-regulated. Theses differently expressed genes were involved in the biological process, cell compartment, molecular functions, and metabolisms of glycine, serine, threonine, and sulfur in pathogen hyphae. Thus, this biocontrol bacterium antagonized B. cinerea in multiple ways due to the production of numerous antifungal substances that acted on multiple targets in the cells. BVFL significantly increased antioxidant enzyme activities in tomato leaves and decreased the incidence of tomato gray mold, with the control efficacies of 73.12–76.51%. Taken together, B. velezensis HY19 showed a promising use potential as a powerful bioagent against tomato gray mold. [Display omitted] [ABSTRACT FROM AUTHOR]

A simple sol–gel method using non-toxic and cost-effective precursors has been developed to prepare graphene oxide (GO)/cellulose bead (GOCB) composites for removal of dye pollutants. Taking advantage of the combined benefits of GO and cellulose, the prepared GOCB composites exhibit excellent removal efficiency towards malachite green (>96%) and can be reused for over 5 times through simple filtration method. The high-decontamination performance of the GOCB system is strongly dependent on encapsulation amount of GO, temperature and pH value. In addition, the adsorption behavior of this new adsorbent fits well with the Langmuir isotherm and pseudo-second-order kinetic model. [ABSTRACT FROM AUTHOR]

Malignant neoplasms exhibit an elevated rate of glycolysis and a high demand for glucose over normal cells. This characteristic can be exploited for in vivo imaging and tumor targeting examined. In this manuscript, we describe the synthesis of near-infrared (NIR) fluorochrome IR-822-labeled 2-amino-2-deoxy- d -glucose (DG) for optical imaging of tumors in mice. NIR fluorescent dye IR-820 was subsequently conjugated with 3-Mercaptopropionic acid and 2-amino-2-deoxy- d -glucose to form IR-822-DG. The cell experiments and acute toxicity studies demonstrated the low toxicity of IR-822-DG to normal cells/tissues. The dynamic behavior and targeting ability of IR-822-DG in normal mice was investigated with a NIR fluorescence imaging system. The in vitro and in vivo tumor targeting capabilities of IR-822-DG were evaluated in tumor cells and tumor bearing mice, respectively. Results demonstrated that IR-822-DG actively and efficiently accumulated at the site of the tumor. The probe also exhibited good photostability and excellent cell membrane permeability. The study indicates the broad applicability of IR-822-DG for tumors diagnosis, especially in the glucose-related pathologies. [ABSTRACT FROM AUTHOR]

Identification of the drug target of lead compounds is an important means for rapid and efficient drug discovery. Protein chips are a high-throughput protein function analysis technology that has been widely used in screening drug protein targets in recent years. However, the verification of the results after high-throughput protein chip screening is still cumbersome. Based on our mature protein chip preparation platform, we prepared a protein chip containing 150 important high-frequency protein targets and used antibodies to prove the availability of the protein chip. To improve the accuracy of target screening, we combined the label-free differential scanning fluorimetry (DSF) with the protein chip, proposing the Chip–DSF strategy. Subsequently, we tested the method with small molecular ginsenoside-Rg2 (Rg2). The Chip–DSF strategy was used to successfully screen the potential target protein KRAS(G12C) of Rg2. Consistently, we found that Rg2 could inhibit NCI-H23 cell proliferation by inducing cell cycle arrest. Also, we found that Rg2 could reduce the amount of KRAS protein and inhibit the phosphorylation of KRAS downstream key signaling protein ERK1, RPS6, and P70S6K in NCI-H23 cells. Collectively, our Chip-DSF strategy could achieve rapid target verification which improved the accuracy and efficiency of target screening of protein chips. [Display omitted] [ABSTRACT FROM AUTHOR]

In China, abortions of donkeys caused by Salmonella have dramatically stifled the growth of the donkey industry. However, pathogenicity of Salmonella linked to abortions in donkeys has not been previously described. Bacteria were isolated and identified from 45 donkeys that experienced abortions, and antibiograms were conducted. Pathogenicity, as median lethal dose (LD 50) in mice was then determined. Furthermore, a mouse abortion model was used to re-create the disease observed in donkeys. The pathologic changes in spleen, liver, intestine and embryo were observed by histological examination. An immunofluorescence assay was used to determine the location and distribution of Salmonella colonization in tissues. A clear link was made between S. abortus equi and abortions in donkeys. The bacterial strains isolated from these cases were either highly or moderately sensitive to the 8 antibiotics tested here. The strain of S. abortus equi isolated here was lethal to mice (LD 50 value is 1.88 × 108 CFU), and caused abortions in pregnant mice. The 50% abortion-causing dose was 1.22 × 108 CFU. Pathological and immunofluorescence data confirmed that the abortions in pregnant mice and donkeys were accompanied by similar disease processes. Therefore, a Salmonella induced abortion model in mice was developed, characterized by abortion, aberrant embryo development, and parenchymal hypoplasia. The mouse abortion model developed here is an important tool for the future characterization and testing therapeutic interventions. • In this work, we isolated the pathogenic bacterium was indeed the cause of abortions in the donkeys. • A Salmonella induced abortion model in mice was developed, The mouse abortion model developed here is an important tool for the future characterization and testing therapeutic interventions. • This study provided insights into the molecular characteristics of Salmonella prevalent of equine in Shandong, China. [ABSTRACT FROM AUTHOR]

Metabolic diseases are becoming increasingly common in modern society. Therefore, it is essential to develop effective drugs or new treatments for metabolic diseases. As an active ingredient derived from plants, celastrol has shown great potential in the treatment of a wide variety of metabolic diseases and received considerable attention in recent years. In reported studies, the anti-obesity effect of celastrol resulted from regulating leptin sensitivity, energy metabolism, inflammation, lipid metabolism and even gut microbiota. Celastrol reversed insulin resistance via multiple routes to protect against type 2 diabetes. Celastrol also showed effects on atherosclerosis, cholestasis and osteoporosis. Celastrol in treating metabolic diseases seem to be versatile and the targets or pathways were diverse. Here, we systematically review the mechanism of action, and the therapeutic properties of celastrol in various metabolic diseases and complications. Based on this review, potential research strategies might contribute to the celastrol's clinical application in the future. [Display omitted] [ABSTRACT FROM AUTHOR]

'Polypharmacology' is usually used to describe the network-wide effect of a single compound, but traditional Chinese medicine (TCM) has a polypharmacological effect naturally based on the 'multi-components, multi-targets and multi-pathways' principle. It is a challenge to investigate the polypharmacology mechanism of TCM with multiple components. In this study, we used XiaoErFuPi (XEFP) granules as an example to describe an unsupervised learning strategy for polypharmacology research of TCM and to explore the mechanism of XEFP polypharmacology against multifactorial disease function dyspepsia (FD). Unsupervised clustering of compounds based on similarity evaluation of cellular function fingerprints showed that compounds of TCM without similar targets and chemical structure could also exert similar therapeutic effects on the same disease, as different targets participate in the same pathway closely associated with the pathological process. In this study, we proposed an unsupervised machine learning strategy for exploring the polypharmacology-based mechanism of TCM, utilizing hierarchical clustering based on cellular functional similarity, to establish a connection from the chemical clustering module to cellular function. Meanwhile, FDA-approved drugs against FD were used as references for the mechanism of action (MoA) of FD. First, according to the compound-compound network built by the similarity of cellular function of XEFP compounds and FDA-approved FD drugs, the possible therapeutic function of TCM may represent a known mechanism of FDA-approved drugs. Then, as unsupervised learning, hierarchical clustering of TCM compounds based on cellular function fingerprint similarity could help to classify the compounds into several modules with similar therapeutic functions to investigate the polypharmacology effect of TCM. Furthermore, the integration of quantitative omics data of TCM and approved drugs (from LINCS datasets) provides more quantitative evidence for TCM therapeutic function consistency with approved drugs. A spasmolytic activity experiment was launched to confirm vanillic acid activity to repress smooth muscle contraction; vanillic acid was also predicted to be active compound of XEFP, supporting the accuracy of our strategy. In summary, the approach proposed in this study provides a new unsupervised learning strategy for polypharmacological research investigating TCM by establishing a connection between the compound functional module and drug-activated cellular processes shared with FDA-approved drugs, which may elucidate the unique mechanism of traditional medicine using FDA-approved drugs as references, facilitate the discovery of potential active compounds of TCM and provide new insights into complex diseases. [ABSTRACT FROM AUTHOR]

Bovine tuberculosis caused by Mycobacterium bovis remains a major cause of economic loss in cattle industries worldwide. However, the pathogenic mechanisms remain poorly understood. Post-translation modifications (PTM) such as phosphorylation play a crucial role in pathogenesis. While the change of transcriptome and proteome during the interaction between M. bovis and cattle were studied, there are no reports on the phosphoproteome change. We apply Tandem Mass Tag-based (TMT) quantitative proteomics coupled with immobilized metal-chelated affinity chromatography (IMAC) enrichment to obtain the quantified phosphorylation in vivo of M. bovis infected cattle lung tissue. The phosphorylated proteins are widespread in the nucleus, cytoplasm and plasma membrane. By using a change fold of 1.2, 165 phosphosites from 147 proteins were enriched, with 88 upregulated and 77 downregulated sites respectively. We further constructed the protein-protein interaction (PPI) networks of STAT3, SRRM2 and IRS-1 based on their number of differential phosphorylation sites and KEGG pathways. Similar patterns of gene expression dynamics of selected genes were observed in Mycobacterium tuberculosis infected human sample GEO dataset, implicating crucial roles of these genes in pathogenic Mycobacteria – host interaction. The first phosphorproteome reveals the relationship between bovine tuberculosis and glucose metabolism, and will help further refinement of target proteins for mechanistic study. Image 1 • Global quantitative phosphoproteome at M. bovis infected cattle lung tissue were explored by TMT coupled with IMAC. • The 1.2-fold cutoff value, 165 phosphosites from 147 proteins were enriched, with 88 upregulated and 77 downregulated sites. • STAT3, SRRM2 and IRS-1 as key factors regulating the glucose metabolism and splicing. • Bovine tuberculosis is closely related to disorders of glucose metabolism. [ABSTRACT FROM AUTHOR]