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Study Question: Does P2X ligand-gated ion channel 3 (P2X3) play a role in endometriosis pain?Summary Answer: Upregulation of P2X3 in dorsal root ganglia (DRG) tissues via the activating transcription factor 3 (ATF3)/activator protein (AP)-1 pathway contributed to endometriosis-associated hyperalgesia, which could be attenuated by the chitosan oligosaccharide stearic acid (CSOSA)/liposomes (LPs)/SP600125 delivery system.What Is Known Already: Infiltrating nerve fibers and elevated nociceptors in endometriotic lesions are associated with endometriosis pain. P2X3 has been demonstrated to play an important role in neuropathic pain.Study Design, Size, Duration: A rat model of endometriosis was used to investigate the signaling pathways involved in P2X3-induced pain.Participants/materials, Setting, Methods: Degrees of hyperalgesia, endogenous adenosine 5'-triphosphate (ATP) contents and P2X3 expression levels in endometriotic lesions and DRG tissues were detected in a rat model of endometriosis. The expression levels of ATF3 and P2X3 were measured using qRT-PCR, western blot analysis and immunofluorescence analysis after adenosine 5'-diphosphate (ADP) exposure in DRG cells. Plasmids encoding ATF3 and its siRNA were used to investigate the role of ATF3 on ADP-induced P2X3 upregulation. The activity of ATF binding to the P2X3 promoter was evaluated by using chromatin immunoprecipitation (CHIP) and luciferase assays. SP600125, an inhibitor of c-JUN N-terminal kinase, was wrapped in CSOSA/LPs delivery system and its inhibitory effects on ADP-induced upregulation of P2X3 in DRG cells and endometriosis-induced hyperalgesia in rats were tested.Main Results and the Role Of Chance: The concentrations of endogenous ATP and expression levels of P2X3 were significantly increased in both endometriotic lesions and DRG tissues in endometriosis rat models and were found to be positively correlated with the severity of hyperalgesia. In DRG cells, P2X3 expression levels were elevated by ADP stimulation, but dramatically inhibited by blocking ATF3 with its siRNA and SP600125. CHIP and luciferase assay showed that ADP increased the binding of ATF3 to the P2X3 promoter, resulting in an increase in P2X3 expression levels. In the CSOSA/LPs/SP600125 delivery system, the drug could be effectively concentrated in endometriotic lesions, and it could alleviate endometriosis-induced hyperalgesia, reduce the size of endometriotic lesions and attenuate upregulated P2X3 expression levels in endometriosis rat models.Large Scale Data: N/A.Limitations, Reasons For Caution: Changes in the sensitivity and function of P2X3 caused by endometriosis need to be further investigated.Wider Implications Of the Findings: This study indicates that ATP and the P2X3 receptor are involved in endometriosis pain, thus providing a novel therapeutic approach for the treatment of endometriosis pain by targeting the P2X3 receptor.Study Funding/competing Interest(s): This work was funded by National Key R&D Program of China (Grant No. 2017YFC1001202) and National Natural Science Foundation of China (Grant Nos. 81974225, 81671429 and 81471433). There are no competing interests. [ABSTRACT FROM AUTHOR]

A simple and sensitive analysis using ultra high performance liquid chromatography with a tandem mass spectrometric system operated in selected reaction monitoring mode was developed for the determination of 11 phenolic acids, atractyloside, and carboxyatractyloside in rat plasma. The two classes of analytes were then separated on a Waters ACQUITY™ UPLC HSS T3 column (50 mm × 2.1 mm, 1.8 µm) using gradient elution with a mobile phase of 0.2% formic acid in water containing 10 mM ammonium acetate and methanol. Detection was accomplished by selected reaction monitoring scanning via an electrospray source operating in negative ionization mode. The calibration curve was linear (R2 = 0.990) over a concentration range of 1.20–3500 ng/mL, while the validated lower limit of quantification was 1.20 ng/mL. The precision varied from 0.84 to 4.62%, and the accuracy varied within ±5%. The method proved robust with sample freezing and thawing and with short‐ and long‐term sample storage. The established method was used for simultaneous quantification and was successfully used for the first time for the pharmacokinetic evaluation of 13 compounds after the intragastric administration of raw and processed Fructus Xanthii in rats. The results indicated that processing affects the absorption and metabolism of Fructus Xanthii extract. Importantly, the results also indicated the importance of processing for the clinical application of traditional Chinese medicine. [ABSTRACT FROM AUTHOR]

Although surgery is an important treatment for laryngeal cancer, surgery has a significant negative impact on the quality of life of patients, and many patients have poor tolerance to surgery. Therefore, alternative chemotherapeutic drugs are an important research hotspot. Chidamide is a histone deacetylase inhibitor that selectively inhibits the expression of type I and IIb histone deacetylases (1, 2, 3 and 10). It has a significant anticancer effect on a variety of solid tumours. This study verified the inhibitory effect of chidamide on laryngeal carcinoma. We conducted a variety of cellular and animal experiments to explore how chidamide inhibits the development of laryngeal cancer. The results showed that chidamide had significant antitumour activity against laryngeal carcinoma cells and xenografts and could induce cell apoptosis, ferroptosis and pyroptosis. This study provides a potential option for the treatment of laryngeal cancer. [Display omitted] [ABSTRACT FROM AUTHOR]

Phenolic acids are important active components of certain Traditional Chinese Medicines (TCM) and have a wide range of biological effects. Separation and purification of phenolic acids remains challenging due to difficulties with quality control using existing chromatographic methods The purpose of this study was to compare the effects of different chromatographic columns and conditions for the separation of phenolic acids. The BEH column was determined to be optimal, providing efficient separation in the shortest time (17.00 min) using gradient elution with carbon dioxide as the mobile phase, methanol/acetonitrile (70:30, v/v) with 1% TFA as the modifier, and a flow rate of 0.8 mL/min. Good peak shapes were obtained, and the peak asymmetry values were close to 1.00 for all phenolic acids. The resolution was more than 2.83 for all separated peaks. The developed method was subsequently applied to the determination of phenolic acids in Xanthii Fructus . These results are beneficial for quality control and standardization of herbal drugs using UPC 2 , providing an efficient, rapid and environmentally friendly scientific basis for future analysis of phenolic acids. [ABSTRACT FROM AUTHOR]

Four novel In3+ and Cd2+ based 1D coordination compounds constructed by double betaine ligands were synthesized and characterized structurally and optically. They assemble into 3D supra‐molecular architectures via different stacking or entanglement of 1D zigzag shaped chains, in which C–H···Cl and C–H···O hydrogen bonding interactions play a dramatic impact. Compound 1 displays a 1D + 1D → 3D four‐connect lvt net with 42·84 topology. Compound 2 assembles into a 3D architecture by inclined stacking of the adjacent zigzag chains. Compound 3 displays a 2D + 2D → 3D inclined polycatenation based on the resulting 2D (6, 3) layers that constructed by 1D chains. Compound 4 displays a 3D supra‐molecular architecture based on 1D chains, which were connected via the hydrogen bonding. Meanwhile, four compounds emit in the range of visible region owing to the intra‐ligand π*→π and/or π*→n electron transition induced florescence. [ABSTRACT FROM AUTHOR]

Abstract As a valuable herbal medicine, the fruits of Xanthium strumarium L. (Xanthii Fructus) have been widely used in raw and processed forms to achieve different therapeutic effects in practice. In this study, a comprehensive strategy was proposed for evaluating the active components in 30 batches of raw and processed Xanthii Fructus (RXF and PXF) samples, based on high-performance liquid chromatography coupled with photodiode array detection (HPLC-PDA). Twelve common peaks were detected and eight compounds of caffeoylquinic acids were simultaneously quantified in RXF and PXF. All the analytes were detected with satisfactory linearity (R2 > 0.9991) over wide concentration ranges. Simultaneously, the chemically latent information was revealed by hierarchical cluster analysis (HCA) and principal component analysis (PCA). The results suggest that there were significant differences between RXF and PXF from different regions in terms of the content of eight caffeoylquinic acids. Potential chemical markers for XF were found during processing by chemometrics [ABSTRACT FROM AUTHOR]

Maca (Lepidium meyenii), a Brassicaceae herb plant originated from Andean mountains, has attracted wide interests due to its unique health benefits in reproduction and fertility. Because of its adaptation to the 4000 m high-altitude harsh environment, maca is attracting more and more attention from both crop breeders and basic biologists. After our previous release of the maca genome sequence, there's a growing need to store, query, analyze and integrate various maca resources efficiently. Here, we created Maca Genome Hub (MGH), a genomics and genetics database of maca. Currently, the MGH V1.0 harbors the genome sequence, predicted coding sequences and protein sequences, various annotations, markers and expression data. For the maca research community, we also provided the publications, researchers and related news. MGH is designed to enable users' easy access to analyze, retrieve and visualize the genomic or genetic information through a series of online tools, including the Basic Local Alignment Search Tool, the JBrowse, the query system, the synteny tool and the data downloads. These integrated heterogeneous data, tools and interfaces in MGH allow efficient mining of the latest genomics and genetics data. We hope that MGH will accelerate the research and development in maca. [ABSTRACT FROM AUTHOR]

The high integration of power information physical system improves the efficiency of power transmission, but it also brings new threats to power grid. False data injection attacks can use traditional bad data to detect vulnerabilities and maliciously tamper with measurement data to affect the state estimation results. In order to achieve a higher security level for power systems, we propose an earth mover distance method to detect false data injection attacks in smart grids. The proposed method is built on the dynamic correlation of measurement data between adjacent moments. Firstly, a joint-image-transformation-based scheme is proposed to preprocess the measurement data variation, so that the distribution characteristics of measurement data variation are more significant. Secondly, the deviation between the probability distribution of measurement data variation and the histogram are obtained based on the earth's mover distance. Finally, a reasonable detection threshold is selected to judge whether there are false data injection attacks. The proposed method is tested using IEEE 14 bus system considering the state variable attacks on different nodes. The results verified that the proposed method has a high detection accuracy against false data injection attacks. [ABSTRACT FROM AUTHOR]

Abstract: This study examines the distributions and potential environmental risk posed by trace elements in various particle size fractions. Element concentrations in soil samples from the study site exceed those of background levels in Beijing, except for Pb and As. The element concentrations generally increased with the decrease of particle size. Both correlation and linear analyses showed positive correlations between element concentrations and organic matter content. The PCA and CA analyses showed that: (1) Cu, Co, Zn, Cd, and V originated from mixed sources; (2) Be, Pb and As came from natural sources and were mainly affected by weathering and erosion of parent rock material; (3) Cr, Ni, and Ba resulted from fine particle pollution; and (4) Hg originated from anthropogenic sources, mainly driven by mining, beneficiation, smelting and acid mine drainage. The Enrichment Factor and Potential ecological harm-indices suggested that the enrichment degree of RI and Er i, increased with the decrease of the particle size, especially for Hg and Cd. This conclusion provides a scientific basis for the prevention of environmental pollution from mining and the protection of the Miyun Reservoir in Beijing. It also provides reference for the further study of trace elements in various particle size fractions internationally. [Copyright &y& Elsevier]

Immunotherapy has emerged as an effective treatment modality for cancer. The interaction of programmed cell death ligand-1 (PD-L1) and programmed cell death protein-1 (PD-1) plays a key role in tumor-related immune escape and has become one of the most extensive targets for immunotherapy. Herein, we investigated the interaction of PD-L1 with its antibody and PD-1 using atomic force microscopy-based single molecule force spectroscopy for the first time. It was found that the PD-L1/anti-PD-L1 antibody complex was easier to dissociate than PD-L1/PD-1. The unbinding forces of specific interaction of PD-L1 on T24 cells with its antibody and PD-1 were quantitatively measured and similar to those on substrate. In addition, the location of PD-L1 on T24 cells was mapped at the single-molecule level by force-volume mapping. The force maps revealed that PD-L1 randomly distributed on T24 cells surface. The recognition events on cells obviously increased after INF-γ treatment, which proved that INF-γ up-regulated the expression of PD-L1 on T24 cells. These findings enrich our understanding of the molecular mechanisms by which PD-L1 interacts with its antibody and PD-1. It provides useful information for the physical factors that is needed to be considered in the design of inhibitors for tumor immunology. [Display omitted] • The interaction of PD-L1 with its antibody and PD-1 was investigated by AFM. • The distribution of PD-L1 on cells was visualized at the single-molecule level. • The effect of INF-γ on PD-L1 expression on cells was quantitatively characterized. • This work provides new insights into the biophysical properties of PD-L1. [ABSTRACT FROM AUTHOR]

Abstract: Histone deacetylase 6 (HDAC6) belongs to the family of class IIb HDACs and predominantly deacetylates non-histone proteins in the cytoplasm via the C-terminal deacetylase domain of its two tandem deacetylase domains. HDAC6 modulates fundamental cellular processes via deacetylation of α-tubulin, cortactin, molecular chaperones, and other peptides. Our previous study indicates that HDAC6 mediates TGF-β1-induced epithelial-mesenchymal transition (EMT) in A549 cells. In the current study, we identify a novel splicing variant of human HDAC6, hHDAC6p114. The hHDAC6p114 mRNA arises from incomplete splicing and encodes a truncated isoform of the hHDAC6p114 protein of 114kDa when compared to the major isoform hHDAC6p131. The hHDAC6p114 protein lacks the first 152 amino acids from N-terminus in the hHDAC6p131 protein, which harbors a nuclear export signal peptide and 76 amino acids of the N-terminal deacetylase domain. hHDAC6p114 is intact in its deacetylase activity against α-tubulin. The expression hHDAC6p114 is elevated in a MCF-7 derivative that exhibits an EMT-like phenotype. Moreover, hHDAC6p114 is required for TGF-β1-activated gene expression associated with EMT in A549 cells. Taken together, our results implicate that expression and function of hHDAC6p114 is differentially regulated when compared to hHDAC6p131. [Copyright &y& Elsevier]

This paper begins from adsorption working pairs: water and ethanol were selected as refrigerants; 13x molecular sieve, silica gel, activated carbon, adsorbent NA and NB, proposed by authors, were selected as adsorbents, and the performance of adsorption working pairs in adsorption refrigeration cycle was studied. The adsorption isotherms of adsorbents (NA and NB) were obtained by high-vacuum gravimetric method. Desorption properties of adsorbents were analyzed and compared by thermal analysis method. The performance of adsorption refrigeration was studied on simulation device of adsorption refrigeration cycle. After presentation of adsorption isotherms, the thermodynamic performance for their use in adsorption refrigeration system was calculated. The results show: (1) the maximum adsorption capacity of water on adsorbent NA reaches 0.7 kg/kg, and the maximum adsorption capacity of ethanol on adsorbent NB is 0.68 kg/kg, which is three times that of ethanol on activated carbon, (2) the refrigeration capacity of NA–water working pair is 922 kJ/kg, the refrigeration capacity of NB–ethanol is 2.4 times that of activated carbon–methanol, (3) as environmental friendly and no public hazard adsorption working pair, NA–H2O and NB–ethanol can substitute activated carbon–methanol in adsorption refrigeration system using low-grade heat source. [Copyright &y& Elsevier]

The aim of this study is to establish a method for rapid screening of active ingredients targeting TNF- α from Chinese herbal medicines. Take Angelicae Pubescentis Radix (APR) as an example, surface plasma resonance technique was used to establish for screening small molecule inhibitors of TNF- α from APR extract. Then UPLC-MS/MS coupled with chemometric was used for quantitative and evaluate the differences of the candidate compounds bound to TNF- α in APR from different sources. In the experiment, TNF- α protein was fixed on the CM5 chip surface of biacore T200 biosensor by amino coupling. A series of small molecular compounds in APR were screened and six phenolic acid compounds had a strong affinity for TNF- α protein and could be used as TNF- α antagonists. In summary, the targeted drug screening method for TNF- α protein based on SPR technology established in this study can be used to screen anti-TNF- α small molecule inhibitors. UPLC-MS/MS can accurately quantify 15 active ingredients, which provides reliable experimental data and new research ideas for targeted drug research on TNF- α protein. Image 1 • A biosensor technology was established for screening inhibitors of TNF- α from APR is firstly proposed. • UPLC-MS/MS combined chemometric was used to analyze and evaluate the differences of the 15 compounds bound to TNF- α in APR. • The affinity test results showed that the selected small molecules had a good affinity with TNF- α. [ABSTRACT FROM AUTHOR]

Farfarae Flos (FF) is the dried flower bud of Tussilago farfara L, which has antitussive, expectorant, and anti-inflammatory effects. However, little research on the main active composition of FF has been reported. The purpose of this study is to find the main active compounds responsible for the three pharmacological effects (i.e., antitussive, expectorant, and anti-inflammatory effects) of Farfarae Flos, based on the spectrum–effect relationship combined with chemometrics. First, this study uses the UPLC-QDA method to establish the chromatography fingerprint of Farfarae Flos, which is combined with chemometrics to analyze 18 batches of samples. Then, we study the antitussive, expectorant, and anti-inflammatory effects of Farfarae Flos. Finally, the spectrum–effect relationship between the fingerprint and the three pharmacological effects are studied by grey correlation analysis and partial least squares regression. The results show that four, four, and three main active constituents were found for the antitussive, expectorant, and anti-inflammatory pharmacological effects, respectively. In conclusion, we found the main active compounds corresponding to the main pharmacodynamic effects of Farfarae Flos. To our knowledge, this is the first time that spectrum–effect relationships in FF have been established using both raw and processed samples, which provides an experimental basis for further studies on the pharmacodynamic material basis of Farfarae Flos, as well as providing reference for the comprehensive evaluation of Farfarae Flos quality and the development of substitute resources. [ABSTRACT FROM AUTHOR]

In the study, a surface plasmon resonance-based (SPR-based) competitive assay was performed to analyze different compounds' inhibitory activity to TNF-α, an important pro-inflammatory cytokine in the pathogenesis of chronic inflammatory diseases. Moreover, the single mass spectrometry (MS) detection method was coupled with an ultra-high-performance liquid chromatography (UPLC) system for the routine quality control (QC) of a traditional Chinese medicine (TCM). The above quality control strategy was evaluated with Lonicera japonica Thunb. Analytes were firstly separated on a Waters ACQUITYTM UPLC HSS T3 column (2.1 × 50 mm; particle size = 1.8 μm) using a 0.1% formic acid gradient elution, then detected by negative ESI mass spectrometry. The limits of quantification (LOQ) for analytes reached 0.005–0.56 μg/mL. The LOD of the QDa detector was lower than that of the PDA detector, indicating its wider detection range. The QDa detector was also more suitable for the analysis of the complex matrix of TCM. The method showed excellent linearity, with regression coefficients higher than 0.9991. The average recoveries of the investigated analytes were in the range of 98.78–105.13%, with an RSD below 3.91%. The inter-day precision range (n = 3 days) was 2.51–4.54%. Compared to other detectors, this strategy could be widely applied in the quantitative analysis of TCM. In addition, the chemically latent data could be revealed using chemometric analysis. Importantly, this study provides an efficient screening method for small-molecule inhibitors targeting the TNF-α pathway. [ABSTRACT FROM AUTHOR]

The purpose of this study was to establish a rapid, reliable, and sensitive ultra-performance liquid chromatography with triple-quadrupole tandem mass spectrometry coupled with chemometric method to measure and evaluate the differences between thirteen compounds in raw and processed Tussilago farfara L. from different sources. This assay method was validated, and the results indicated that the calibration curves for the thirteen compounds had good linearity (R2 > 0.9990). The limits of detection and limits of quantification of the thirteen compounds ranged from 0.0012 to 0.0095 μg/mL and from 0.0038 to 0.0316 μg/mL, respectively. The relative standard deviations (RSD) of the intra- and inter-day precisions and stability ranged from 1.06 to 2.00%, 0.26 to 1.99%, and 0.75 to 1.97%, respectively. The sample recovery rates of the thirteen compounds with different concentrations were 94.47–104.06%. The chemometric results, including principal component analysis, hierarchical clustering analysis, three-dimensional analysis, and box plot analysis, indicated that there are significance differences in raw and processed Tussilago farfara L. The results of this study confirm that the proposed method is the first reported method that has been successfully applied for simultaneous determination and discovery of the difference between thirteen compounds of raw and processed Tussilago farfara L. Thus, this method could be a helpful tool for the detection and confirmation of the quality of traditional Chinese medicines and provide a basis for future pharmacological studies. [ABSTRACT FROM AUTHOR]

An accurate and reliable method using ultra-high performance liquid chromatography combined with triple quadrupole tandem mass spectrometry (UHPLC–MS/MS) was established for simultaneous quantification of five major bioactive analytes in raw, wine-processed, and salt-processed Radix Achyranthis bidentatae (RAB). The results showed that this method exhibited desirable sensitivity, precision, stability, and repeatability. The overall intra-day and inter-day variations (RSD) were in the range of 1.57–2.46 and 1.51–3.00%, respectively. The overall recoveries were 98.58–101.48% with a relative standard deviation (RSD) of 0.01–1.86%. In addition, the developed approach was applied to 21 batches of raw, wine-processed, and salt-processed samples of RAB. Hierarchical clustering analysis (HCA), principal component analysis (PCA), heat map, and boxplot analysis were performed to evaluate the quality of raw, wine-processed, and salt-processed RAB collected from different regions. The chemometrics combined with the quantitative analysis based on UHPLC–MS/MS results indicated that the content of five analytes increased significantly in processed RAB compared to raw RAB. [ABSTRACT FROM AUTHOR]