Aqueous degradation of tioxazafen: Kinetics, products, pathways, and toxicity.

Tioxazafen (TXF) is the first 1,2,4-oxadiazole nematicide. In the present study, the aqueous degradation of TXF was investigated in terms of hydrolysis and photolysis. Under the irradiation of simulated sunlight, TXF degraded very fast in ultrapure water and buffers with half-lives (t1/2s) <8.3 min. A sole photoproduct (PP) PP228a was isolated, and identified by spectroscopic means (UV, IR, HRMS, and 1H NMR) to be the thiophen-3-yl isomer converted from its thiophen-2-yl parent. Comparing with TXF, PP228a had quite extended t1/2s ranging from 6.9 to 7.9 d. The photolysis kinetics of TXF and PP228a showed no pH-dependence, and varied for each individual compound as affected by nitrate, fulvic acid, and humic acid. Besides, both compounds were hydrolytically stable. 6 PPs of PP228a were identified, with two of them being its isomers. The mechanisms involved in the process included the biradical photosensitization, photoinduced electron transfer, and ring contraction-ring expansion reactions. The 48 h-EC50 to Daphnia magna was 0.808 mg/L for PP228a comparing to >1.12 mg/L for TXF, while the results of Vibrio fischeri assays indicated that one or more PPs of PP228a might have higher toxicity.

Identification and validation of three potential biomarkers and immune microenvironment for in severe asthma in microarray and single-cell datasets.

Objective: The aim of this study was to identify genetic biomarkers and cellular communications associated with severe asthma in microarray data sets and single cell data sets. The potential gene expression levels were verified in a mouse model of asthma.Methods: We identified differentially expressed genes from the microarray datasets (GSE130499 and GSE63142) of severe asthma, and then constructed models to screen the most relevant biomarkers to severe asthma by machine learning algorithms (LASSO and SVM-RFE), with further validation of the results by GSE43696. Single-cell datasets (GSE193816 and GSE227744) were identified for potential biomarker-specific expression and intercellular communication. Finally, The expression levels of potential biomarkers were verified with a mouse model of asthma.Results: The 73 genes were differentially expressed between severe asthma and normal control. LASSO and SVM-RFE recognized three genes BCL3, DDIT4 and S100A14 as biomarkers of severe asthma and had good diagnostic effect. Among them, BCL3 transcript level was down-regulated in severe asthma, while S100A14 and DDIT4 transcript levels were up-regulated. The transcript levels of the three genes were confirmed in the mouse model. Infiltration of neutrophils and mast cells were found to be increased in severe asthma and may be associated with bronchial epithelial cells through BMP and NRG signalingConclusions: We identified three differentially expressed genes (BCL3, DDIT4 and S100A14) of diagnostic significance that may be involved in the development of severe asthma and these gene expressions could be serviced as biomarker of severe asthma and investigating the function roles could bring new insights into the underlying mechanisms.

Exploring the therapeutic mechanisms of Sijunzi decoction in the treatment of sarcopenia: Key targets and signaling pathways.

Sarcopenia, an age-associated condition, negatively impacts the quality of life. This study investigates the mechanism of Sijunzi decoction (SJZD), a traditional Chinese formula, against sarcopenia. Active compounds and potential targets of SJZD for sarcopenia were gathered from databases. Hub targets were identified using protein-protein interaction networks, with GO and KEGG analyses suggesting potential pathways. Molecular docking was used to assess compound-target affinity. A lipopolysaccharide-induced sarcopenia rat model was used to verify the targets. Sijunzi decoction contains 92 compounds and 47 targets for sarcopenia. The top 10 hub targets comprise AKT1, ALB, INS, IL6, TNF, TP53, VEGFA, SIRT1, CAT and FOS. GO and KEGG analyses indicate involvement in steroid hormone response, vesicle lumen, receptor agonist activity, and FoxO and HIF-1 signaling pathways. Validation experiments showed that SJZD alleviates sarcopenia by downregulating SIRT1, IL-6, TNF and AKT1. Sijunzi decoction treats sarcopenia by targeting SIRT1, IL-6, TNF and AKT1, potentially involving FoxO and HIF-1 signaling pathways. This highlights SJZD's potential for sarcopenia treatment.

Characteristics of organic pollutants and their effects on the microbial composition and activity in the industrial soils of Pearl River Delta, China.

To investigate the interaction between organic pollutants and soil microorganisms, industrial soils were collected from Pearl River Delta region of China for determining semi-volatile organic pollutants, the community structure and activity of microorganisms. The results showed that polycyclic aromatic hydrocarbons (PAHs) (63.3-4956 µg kg-1) and phthalate esters (PAEs) (272-65,837 µg kg-1) were main organic pollutants in the research area soils. Chemical manufacturing industry and plastics manufacturing industry contributed greatly to PAH pollution and PAE pollution, respectively. Organic pollutants changed the biomass of microorganisms. In most industrial soils, the biomass of actinomycetes was the highest in the industrial soils, followed by G- bacteria, G+ bacteria and fungi. The exception was that the biomass of fungi in the soil near chemical manufacturing industry was greater than that of G+ bacteria. The soil microbial biomass (including soil microbial biomass carbon, soil microbial biomass nitrogen, the biomass of actinomycetes, bacteria, and fungi) and soil enzyme activities (sucrase and urease) positively correlated with the organic pollutant residues, and the microbial species diversity and microbial species abundance decreased with organic pollutant residues increasing. Based on the correlation analysis, the urease activity, actinomycetes biomass, and fungi biomass were appropriate biological indicators for evaluating the stress of organic pollutants. Our research provides a new perspective for understanding the soil biological response in industrial soils.

Contribution of dicarboxylic acids to pyrene biodegradation and transcriptomic responses of Enterobacter sp. PRd5.

The colonization of degrading endophytic bacteria is an effective means to reduce the residues of polycyclic aromatic hydrocarbons (PAHs) in crops. Dicarboxylic acids, as the main active components in crops, can affect the physiological activities of endophytic bacteria and alter the biodegradation process of PAHs in crops. In this study, malonic acid and succinic acid were selected as the representatives to investigate the contribution of dicarboxylic acids to pyrene biodegradation by endophytic Enterobacter sp. PRd5 in vitro. The results showed that dicarboxylic acids improved the biodegradation of pyrene and altered the expression of the functional gene of strain PRd5. Malonic acid and succinic acid reduced the half-life of pyrene by 20.0% and 27.8%, respectively. The degrading enzyme activities were significantly stimulated by dicarboxylic acids. There were 386 genes up-regulated and 430 genes down-regulated in strain PRd5 with malonic acid, while 293 genes up-regulated and 340 genes down-regulated with succinic acid. Those up-regulated genes were distributed in the functional classification of signal transduction, membrane transport, energy metabolism, carbohydrate metabolism, and amino acid metabolism. Malonic acid mainly enhanced the central carbon metabolism, cell proliferation, and cell activity. Succinic acid mainly improved the expression of degrading gene. Overall, the findings of this study provide new insights into the regulation and control of PAH stress by crops. KEY POINTS: • Dicarboxylic acids improved the biodegradation of pyrene by Enterobacter sp. PRd5. • The degrading enzyme activities were stimulated by dicarboxylic acids. • There are different facilitation mechanisms between malonic acid and succinic acid.

Afterglow Implant for Arterial Embolization and Intraoperative Imaging.

Transcatheter arterial embolization (TAE) is wildly used in clinical treatments. However, the online monitoring of the thrombosis formation is limited due to the challenges of the direct visualization of embolic agents and the real-time monitoring of dynamic blood flow. Thus, we developed a photochemical afterglow implant with strong afterglow intensity and a long lifetime for embolization and imaging. The liquid pre-implant injected into the abdominal aorta of mice was rapidly transformed into a hydrogel in situ to embolize the blood vessel. The vascular embolism position can be observed by the enhanced afterglow of the fixed implant, and the long lifetime of afterglow can also be used to monitor the effect of embolization. This provides an excellent candidate in bio-imaging to avoid the autofluorescence interference from continuous light excitation. The study suggests the potential usefulness of the implant as an embolic agent in TAE and artery imaging during a surgical procedure.

Chinese Stroke Center Alliance: a national effort to improve healthcare quality for acute stroke and transient ischaemic attack: rationale, design and preliminary findings.

Background: In June 2015, the Chinese Stroke Association (CSA) initiated the Chinese Stroke Center Alliance (CSCA) to establish the national hospital-based stroke care quality assessment and improvement platform. This article outlines its objectives, operational structure, patient population, quality improvement (QI) intervention tools, data elements, data collection methodology and current patient and hospital data. Methods: The CSCA is a national, hospital-based, multicentre, voluntary, multifaceted intervention and continuous QI initiative. This multifaceted intervention includes stroke centre development, written care protocols, workshops and a monitoring/feedback system of evidence-based performance measures. The data coordinating centre of the CSCA resides at the China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital. Results: As of July 2017, 1576 hospitals in China have contributed detailed clinical information to serve as a benchmark for the stroke care quality of 433 264 patients with acute stroke/transient ischaemic attacks (TIA), including 352 572 (81.38%) acute ischaemic stroke, 30 362 (7.01%) TIA, 42 080 (9.71%) spontaneous intracranial haemorrhage, 5505 (1.27%) subarachnoid haemorrhage and 2745 (0.63%) not specified stroke. Conclusion: The CSCA programme is designed to establish a continuous national stroke registry and help healthcare providers develop stroke centres and treat patients in a consistent manner in accordance with accepted national guidelines and, ultimately, improve patient outcomes. It supports the CSA mission to reduce stroke burden in China.

Inhibition of 5-lipoxygenase and cyclooxygenase-2 pathways by pain-relieving plaster in macrophages.

CONTEXT: Pain-relieving plaster (PRP) is a traditional Chinese medicine (TCM) that has been widely used with satisfactory results in the treatment of some diseases related to inflammation, such as bruises, chronic arthritis. OBJECTIVE: The mechanisms underlying the anti-inflammatory actions of PRP are investigated in this study for the first time. MATERIALS AND METHODS: The anti-inflammatory effects of PRP extracts were evaluated in lipopolysaccharide (LPS) or calcium ionophore A23187-treated murine peritoneal macrophages (PMs). Tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), prostaglandin E2 (PGE2), and leukotrienes B4 (LTB4) were evaluated by ELISA assays. Reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot analysis were used to detect the expression of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX). Nuclear factor-kappa B (NF-κB)-DNA-binding activity was determined by gel mobility shift assay. RESULTS: PRP extracts were found to inhibit the production of TNF-α, IL-1ß, and PGE(2), reduce the expressions of COX-2 at the mRNA and protein levels induced by LPS, and reduced the production of LTB4 induced by A23187. Furthermore, PRP extracts significantly attenuated LPS-induced NF-κB-DNA-binding activity. DISCUSSION AND CONCLUSION: The anti-inflammatory effects of PRP possibly are related to reduction of inflammatory cytokines (TNF-α and IL-1ß), inducible inflammatory enzyme (COX-2), and its metabolite PGE2 via NF-κB signal pathway. Moreover, PRP extracts also notably inhibited the production of LTB4, indicating that PRP inhibited the 5-LOX pathway, which may be the other mechanism for its anti-inflammatory action.

Effect of ginkgolide B on the platelet-activating factor induced changes of chemotaxis and cytoskeleton of macrophages.

AIM: To study the inhibitory effect of ginkgolide B (BN52021) on the PAF induced changes of chemotaxis of murine peritoneal macrophages and the related polymerization of F-actin. METHODS: Chemotaxis assays were performed using a modified 48-well Boyden chamber. Actin polymerization of murine peritoneal macrophages was analyzed by flow cytometry using a specific fluorescent stain. RESULTS: Peritoneal macrophages significantly migrated toward platelet-activating factor (PAF) through a micropore filter; however, in the presence of PAF receptor antagonist BN52021 (0.01 nmol x L(-1) -0.1 micromol x L(-1)), the migration was significantly inhibited. Moreover, BN52021 inhibited the actin polymerization of murine peritoneal macrophages induced by PAF in the presence of Ca2+, but not in Ca2+ -free medium. CONCLUSION: The results suggested that preventing polymerization of F-actin may be a pathway by BN52021 to inhibit the chemotaxis of macrophages, and this effect seems to be Ca2+ dependent. The data further indicated that inhibition of PAF induced macrophage chemotaxis is an important mechanism underlying the anti-inflammatory action of BN52021.