[Prediction and analysis of Q-markers of Elephantopus scaber based on its UPLC fingerprint, content determination of components, and in vitro a nti-tumor activity].

This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 µm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 ℃, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 µL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 µmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.

A fast and accurate method for the pharmacokinetic research of four coumarin analogs in Fructus cnidii using capillary electro-chromatography with a methacrylate ester-based monolithic column.

In the present study, a monolithic capillary column with higher permeability was developed for the in vivo discrimination of four coumarin analogs (bergapten, 2'-acetylangelicin, imperatorin, and osthole) that typically require long separation times in HPLC. Instead of conventional methacrylate ester monolith (containing 19.5% porogen) with insufficient permeability (K = 1.52 - 1.66 × 10-14 M2 ) for plasma sample, the proposed column (20.5% porogen) had better permeability (around 3.80 × 10-14 M2 ) while properties such as pore distribution, stability, and resolution changed slightly. As a result, due to the negatively charged electro-dynamic flow of the methacrylate ester groups in the monolith, the migration of targeted analytes was achieved within 6 min (compared with 30 min in HPLC) with acceptable resolution and improved sensitivity (0.005-0.02 µg/mL vs. 0.04 µg/mL). The proposed method was also applied to pharmacokinetic research: accelerated solvent extraction (ASE) was used to improve the extraction efficiency, which prepared extract much faster and more pure than conventional methods. As the pharmacokinetic parameters indicated, the monolithic capillary electro-chromatography method was efficient, sensitive, specific, and durable, guaranteeing its utility for the determination of multiple structure-related compounds in rat plasma.

Application and optimization of organic-inorganic hybrid monolithic capillary electrochromatography for in vivo cefdinir determination with microdialysis.

In this study, an organic-inorganic hybrid monolithic capillary column was applied and optimized for the determination of cefdinir in plasma, and the electro-osmotic flow that usually hinders migration in reverse polarity became a driving force. The Sample used for pharmacokinetic research was collected by microdialysis using phosphate buffer (pH 7.4) as perfusate, and a volume of 60 µL fluid was mixed with 140 µL of acetonitrile. By using a silica-allyldimethyldodecylammonium monolithic column (100 µm inner diameter, 21 cm effective length and 31.2 cm total length), and a mobile phase consisting of phosphate and acetonitrile (pH 4.5, 50:50, v/v), at a voltage of 20 kV, the analytes were successfully separated with the background within 2.5 min. The detection wavelength was 214 nm. The calibration curve showed a good linearity (r(2) = 0.9994) over the concentration range of 0.2-50 µg/mL. The proposed method showed good specificity, linearity, sensitivity, precision and recovery, and the introduction of field amplified sample stacking helped to improve the low recovery caused by microdialysis. This method was successfully applied to quantify cefdinir in rat plasma to support a pre-clinical pharmacokinetic trial.

Screening and Validation of Key Genes of Autophagy in Acute Myocardial Infarction Based on Bioinformatics.

Aims: Autophagy plays a significant role in the development of acute myocardial infarction (AMI), and cardiomyocyte autophagy is of major importance in maintaining cardiac function. We aimed to identify key genes associated with autophagy in AMI through bioinformatics analysis and verify them through clinical validation. Materials and Methods: We downloaded an AMI expression profile dataset GSE166780 from Gene Expression Omnibus (GEO). Autophagy-associated genes potentially differentially expressed in AMI were screened using R software. Then, to identify key autophagy-related genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, protein-protein interaction (PPI) analysis, Receiver Operating Characteristic (ROC) curve analysis, and correlation analysis were performed on the differentially expressed autophagy-related genes in AMI. Finally, we used quantificational real-time polymerase chain reaction (qRT-PCR) to verify the RNA expression of the screened key genes. Results: TSC2, HSPA8, and HIF1A were screened out as key autophagy-related genes. qRT-PCR results showed that the expression levels of HSPA8 and TSC2 in AMI blood samples were lower, while the expression level of HIF1A was higher than that in the healthy controls. Conclusions: TSC2, HSPA8, and HIF1A were identified as key autophagy-related genes in this study. They may influence the development of AMI through autophagy. These findings may help deepen our understanding of AMI and may be useful for the treatment of AMI.

A novel and sensitive method for simultaneous determination of 6 low-calorie bulk sweeteners by HPLC-ELSD.

A novel and sensitive method for the simultaneous analysis of six low-calorie bulk sweeteners (D-allulose, D-tagatose, D-mannitol, mycose, palatinose, and erythritol) without derivatisation was developed using high-performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD). Chromatographic separations were carried out on a Zorbax Original NH2 (5 µm particle size, 250 mm×4.60 mm id, 70 Å) column with flow rate gradient elution with acetonitrile: water (80:20, v/v). Drift tube temperature was set at 50 ℃, the nebuliser carrier gas flow rate was 1.0 mL·min-1, and nitrogen pressure was regulated to 276 kPa with gain:3. The regression equation showed good linearity (R2 = 0.9985-0.9998) for all six low-calorie bulk sweeteners in the tested range (0.060-0.60 mg·mL-1). The limits of detection (LOD) for the six low-calorie bulk sweeteners ranged from 0.02 to 0.06 mg·mL-1. The proposed HPLC-ELSD method was validated for the quantification of the low-calorie bulk sweeteners in 14 types of foods, and the results were satisfactory. In addition, the results showed that the number of sweeteners in each food product varied. The presence of multiple low-calorie bulk sweeteners in certain foods is interesting. This method is successful in monitoring low-calorie bulk sweeteners in food.

Investigation into the anti-inflammatory mechanism of Pothos chinensis (Raf.) Merr. By regulating TLR4/MyD88/NF-κB pathway: Integrated network pharmacology, serum pharmacochemistry, and metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Inflammation is directly related to disease progression and contributes significantly to the global burden of disease. Pothos chinensis (Raf.) Merr. (PCM) is commonly used in Yao medicine in China to treat tumors, and orthopedic illnesses such as knee osteoarthritis, and rheumatic bone discomfort. PCM was found to have significant anti-inflammatory properties in previous studies. AIM OF THE STUDY: To explore the active compounds of PCM and their anti-inflammatory pharmacological mechanisms through an integrated strategy of serum pharmacochemistry, network pharmacology, and serum metabolomics. MATERIALS AND METHODS: The qualitative and quantitative analyses of the chemical components of PCM were performed using UPLC-QTOF-MS/MS and UPLC, respectively, and the prototype components of PCM absorbed into the blood were analyzed. Based on the characterized absorbed into blood components, potential targets and signaling pathways of PCM anti-inflammatory were found using network pharmacology. Furthermore, metabolomics studies using UPLC-QTOF-MS/MS identified biomarkers and metabolic pathways related to the anti-inflammatory effects of PCM. Finally, the hypothesized mechanisms were verified by in vivo and in vitro experiments. RESULTS: Forty chemical components from PCM were identified for the first time, and seven of them were quantitatively analyzed, while five serum migratory prototype components were found. Network pharmacology KEGG enrichment analysis revealed that arachidonic acid metabolism, Tyrosine metabolism, TNF signaling pathway, NF-κB signaling pathway, and phenylalanine metabolism were the main signaling pathways of PCM anti-inflammatory. Pharmacodynamic results showed that PCM ameliorated liver injury and inflammatory cell infiltration and downregulated protein expression of IL-1ß, NF-κB p65, and MyD88 in the liver. Metabolomics studies identified 53 different serum metabolites, mainly related to purine and pyrimidine metabolism, phenylalanine metabolism, primary bile acid biosynthesis, and glycerophospholipid metabolism. The comprehensive results demonstrated that the anti-inflammatory modulatory network of PCM was related to 5 metabolites, 3 metabolic pathways, 7 targets, and 4 active components of PCM. In addition, molecular docking identified the binding ability between the active ingredients and the core targets, and the anti-inflammatory efficacy of the active ingredients was verified by in vitro experiments. CONCLUSION: Our study demonstrated the anti-inflammatory effect of PCM, and these findings provide new insights into the active ingredients and metabolic mechanisms of PCM in anti-inflammation.

ESL attenuates BLM-induced IPF in mice: Dual mediation of the TLR4/NF-κB and TGF-ß1/PI3K/Akt/FOXO3a pathways.

BACKGROUNDS: Idiopathic pulmonary fibrosis (IPF) is a persistent and advanced pulmonary ailment. The roles of innate immunity and adaptive immunity are pivotal in the evolution of IPF. An ill-adjusted interaction between epithelial cells and immune cells is responsible for initiating the epithelial-mesenchymal transition (EMT) process and sustaining chronic inflammation, thereby fostering fibrosis progression. The intricacy of IPF pathogenesis has hindered the availability of efficacious agents. Elephantopus scaber Linn. (ESL) is a canonical Chinese medicine with significant immunoregulatory effects, and its aqueous extract has been proven to attenuate IPF symptoms in bleomycin (BLM)-induced mice. However, the underlying mechanism through which ESL relieves IPF remains unclear. AIM: To validate whether ESL reverses IPF by mediating the immune response and EMT. METHODS: Ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) and UPLC were used to identify the components and determine the concentrations of the specific compounds in the ESL. Network pharmacology and molecular docking were applied to predict the potential mechanism underlying the anti-IPF effect of ESL. BLM-induced IPF mice were used to validate the anti-IPF effect of ESL, and lung tissue was collected to test putative pathways involved in inflammation and EMT via immunohistochemistry (ICH), real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting. RESULTS: Sixty-one compounds were identified, and thirteen main ingredients were quantified in the ESL. In silico experiments predicted that the IPF-mediated reversal of adverse effects by ESL would be related to interruption of the Toll-like receptor 4 (TLR4)/nuclear factor-k-gene binding (NF-ĸB) inflammatory pathway and the transforming growth factor-beta l (TGF-ß1)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/forkhead box O3 (FOXO3a) fibrosis pathway. In vivo experiments showed that ESL alleviates BLM-induced lung inflammation and fibrosis by reducing neutrophil aggregation and fibroblast foci, similar to the effects of the positive control drug pirfenidone (PFD). ESL markedly inhibited the transcription of TNF-α, IL-1ß, and IL-6, which are downstream genes of the NF-κB signaling pathway. Furthermore, the protein levels of TLR4 and p-NF-κB were correspondingly inhibited in response to ESL treatment. Additionally, ESL reverses BLM-induced changes in the expression of EMT-related biological characteristic indicators (collagen I [COLIA1], E-cadherin, and alpha smooth muscle actin [α-SMA]) at the messenger ribonucleic acid (mRNA) level and markedly inhibits the expression of EMT-related upstream proteins (TGF-ß1, p-PI3K, p-Akt, and p-FOXO3a). CONCLUSION: Our research suggested that ESL attenuates BLM-induced IPF through mediating the EMT process via the TGF-ß1/PI3K/Akt/FOXO3a signaling pathway and inhibiting inflammation through the TLR4/NF-κB signaling pathway, highlighting that ESL can serve as an immunoregulator for relieving the abnormal immune response and reversing the EMT in IPF.

Spatial-temporal dynamics of NDVI and Chl-a concentration from 1998 to 2009 in the East coastal zone of China: integrating terrestrial and oceanic components.

Annual normalized difference vegetation index (NDVI) and chlorophyll-a (Chl-a) concentration are the most important large-scale indicators of terrestrial and oceanic ecosystem net primary productivity. In this paper, the Sea-viewing Wide Field-of-view Sensor level 3 standard mapped image annual products from 1998 to 2009 are used to study the spatial-temporal characters of terrestrial NDVI and oceanic Chl-a concentration on two sides of the coastline of China by using the methods of mean value (M), coefficient of variation (CV), the slope of unary linear regression model (Slope), and the Hurst index (H). In detail, we researched and analyzed the spatial-temporal dynamics, the longitudinal zonality and latitudinal zonality, the direction, intensity, and persistency of historical changes. The results showed that: (1) spatial patterns of M and CV between NDVI and Chl-a concentration from 1998 to 2009 were very different. The dynamic variation of terrestrial NDVI was much mild, while the variation of oceanic Chl-a concentration was relatively much larger; (2) distinct longitudinal zonality was found for Chl-a concentration and NDVI due to their hypersensitivity to the distance to shoreline, and strong latitudinal zonality existed for Chl-a concentration while terrestrial NDVI had a very weak latitudinal zonality; (3) overall, the NDVI showed a slight decreasing trend while the Chl-a concentration showed a significant increasing trend in the past 12 years, and both of them exhibit strong self-similarity and long-range dependence which indicates opposite future trends between land and ocean.

[Effect of early intervention of liver-smoothing and blood-activating decoction combined with acupuncture on patients with post-stroke depression].

To study the effect of early intervention of liver-soothing and Blood-activating decoction combined with acupuncture in improving neurological functions, depressive symptom and life quality of patients with post-stroke depression, and compare with fluoxetine hydrochloride. Specifically, 63 patients with post-stroke depression were randomly divided into the traditional Chinese medicine (TCM) acupuncture group (31 cases) and the western medicine group (32 cases). On the basis of the conventional treatment of the primary disease, the TCM acupuncture group was treated with liver-soothing and blood-activating decoction and acupuncture, while the western medicine group was treated with fluoxetine hydrochloride for four weeks. In the follow-up visit six months later, scores of HAMD, NIHSS and SS-QOL were observed. The scores of HAMD and NIHSS of both groups were significantly decreased (P < 0.01), while the scores of SS-QOL increased significantly, with a notable difference compared with that before the treatment (P < 0.01). Specifically, the TCM acupuncture group's was superior to the western medicine group (P < 0.05). The study suggests that the early intervention of liver-soothing and blood-activating decoction combined with acupuncture on patients with post-stroke depression has the effect in relieving depression symptom and improving neurological functions, thereby improving their quality of life and prognosis.

A novel quantification method of lung fibrosis based on Micro-CT images developed with the optimized pulmonary fibrosis mice model induced by bleomycin.

Background and aims: Idiopathic pulmonary fibrosis (IPF) is a fibrosing lung disease with unknown etiology, leading to cough and dyspnoea, which is also one of the most common sequelae affecting the quality of life of COVID-19 survivors. There is no cure for IPF patients. We aim to develop a reliable IPF animal model with quantification of fibrosis based on Micro-Computer Tomography (micro-CT) images for the new drug discovery, because different bleomycin administration routes, doses, and intervals are reported in the literature, and there is no quantitative assessment of pulmonary fibrosis based on micro-CT images in animal studies. Methods: We compared three dosages (1.25 mg/kg, 2.5 mg/kg, and 5 mg/kg) of intratracheal bleomycin administration and experiment intervals (14 and 21 days) in C57BL/6 mice by investigating survival rates, pulmonary histopathology, micro-CT, peripheral CD4+ & CD8+ cells, and cytokines. Moreover, a simple and reliable new method was developed for scoring fibrosis in live mice based on Micro-CT images by using Image J software, which transfers the dark sections in pulmonary Micro-CT images to light colors on a black background. Results: The levels of hydroxyproline, inflammation cytokine, fibrotic pathological changes, and collagen deposition in the lungs of mice were bleomycin dose-dependent and time-dependent as well as the body weight loss. Based on the above results, the mice model at 21 days after being given bleomycin at 1.25 mg/kg has optimal pulmonary fibrosis with a high survival rate and low toxicity. There is a significant decrease in the light area (gray value at 9.86 ± 0.72) in the BLM mice, indicating that a significant decrease in the alveolar air area was observed in BLM injured mice compared to normal groups (###p < 0.001), while the Pirfenidone administration increased the light area (gray value) to 21.71 ± 2.95 which is close to the value observed in the normal mice (gray value at 23.23 ± 1.66), which is consistent with the protein levels of Col1A1, and α-SMA. Notably, the standard deviations for the consecutive six images of each group indicate the precision of this developed quantitation method for the micro-CT image taken at the fifth rib of each mouse. Conclusion: Provided a quantifying method for Micro-CT images in an optimal and repeatable pulmonary fibrosis mice model for exploring novel therapeutic interventions.

Herbal formula Jiawei Xiaochengqi decoction prevents postoperative abdominal adhesion in a rat model through inhibition of CXCL2-CXCR2 pathway.

BACKGROUND: Postoperative abdominal adhesion (PAA) is the most common complication after abdominal surgeries, which can lead to intestinal obstruction, chronic abdominal pain or female infertility. Jiawei Xiaochengqi decoction (JWXCQ) is a hospital preparation widely used for PAA treatment in Nanfang Hospital of Southern Medical University for more than twenty years. PURPOSE: This study aimed to investigate the therapeutic effects and potential mechanism of JWXCQ against PAA and provide beneficial information for its clinical application. METHODS: The main active components of JWXCQ were identified using ultra high performance liquid chromatography (UHPLC) combined with standard substance comparison. The efficacy and underlying mechanism of JWXCQ were evaluated through in vivo experiments with a postsurgical-induced peritoneal adhesion rat model, and in vitro studies with LPS-stimulated Raw 264.7 macrophages and primary fibroblasts. H&E and Masson staining were performed to assess histopathological changes. The levels of cytokines/proteins-associated with inflammation and degradation of extracellular matrix as well as CXCL2-CXCR2 pathway-related proteins were determined by ELISA, qRT-PCR, western blot assays or immunohistochemistry, respectively. Furthermore, siCXCR2 transfection was used to validate the mechanism of action of JWXCQ. RESULTS: JWXCQ treatment significantly reduced the formation of PAA, inhibited the inflammation and collagen deposition, and facilitated the secretion of MMP9, decreased the levels of IL-1ß, IL-6, TIMP1, COL-1, and suppressed the CXCL2-CXCR2 pathway in PAA rats. Furthermore, JWXCQ inhibited its downstream pathways, the JAK2-STAT3 and PI3K-AKT signaling, as indicated by the suppression of the phosphorylation levels of STAT3 and AKT. In vitro cell experiments revealed that JWXCQ reduced IL-1ß and IL-6 secretion in Raw 264.7 macrophages and COL-1 in primary fibroblasts. The CXCL2-CXCR2, JAK2-STAT3 and PI3K-AKT pathways were also inhibited after JWXCQ treatment, which were consistent with the in vivo results. More importantly, silence of CXCR2 eliminated the regulatory effects of JWXCQ. CONCLUSION: JWXCQ could effectively prevent the PAA formation by alleviating inflammation and collagen deposition, which was associated with the inhibition of CXCL2-CXCR2 pathway. This study investigated the relevant pharmacological mechanisms of JWXCQ, providing further evidence for the application of JWXCQ in clinical PAA treatment.

Metabolomics analysis delineates the therapeutic effects of Yinlan Tiaozhi capsule on triton WR-1339 -induced hyperlipidemia in mice.

Hyperlipidemia is a disorder of lipid metabolism resulting from abnormal blood lipid metabolism and is one of the most frequent metabolic diseases that endanger people's health. Yinlan Tiaozhi capsule (YL) is a formulated TCM widely used to treat hyperlipidemia. The purpose of this study was to discover biomarkers utilizing untargeted metabolomics techniques, as well as to analyze the mechanisms underlying the changes in metabolic pathways linked to lipid-lowering, anti-inflammation, and regulation of angiogenesis in hyperlipidemia mice. To assess the efficacy of YL, serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) levels were measured. Biochemical examinations showed that YL significantly reduced the levels of TC, TG, LDL-c, Il6, Tnf-α, and Vegfa in hyperlipidemia mice (p < 0.01). YL also significantly increased the levels of HDL-c and Alb (p < 0.01). Twenty-seven potential serum biomarkers associated with hyperlipidemia were determined. These differential metabolites were related to the reduction of serum lipid levels in hyperlipidemia mice, probably through metabolic pathways such as linoleic acid metabolism, glycerophospholipid metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and D-glutamine and D-glutamate metabolism. Further correlation analysis showed that the serum lipid reduction through YL was related to the metabolites (amino acid metabolites, phospholipids metabolites, and fatty acids metabolites). The present study reveals that YL has a profound effect on alleviating triton WR-1339-induced hyperlipidemia, inflammation, and angiogenesis and that the positive effects of YL were primarily associated with the correction of metabolic abnormalities and the maintenance of metabolite dynamic balance.

Integrated network pharmacology and metabolomics reveal the mechanisms of Jasminum elongatum in anti-ulcerative colitis.

Jasminum elongatum (JE), an ethnic Chinese medicine, is widely used in the Lingnan region of China, because of its analgesic and antidiarrheal action, as well as its anti-inflammatory effects in gastrointestinal diseases. However, whether JE could against ulcerative colitis (UC) remains unclear. This research aims to reveal JE in treating UC and clarify the underlying mechanism. We used the 2.5% dextran sulfate sodium (DSS)-induced UC mice (C57BL/6J) to evaluate the therapeutic effects of JE. Metabolomics of serum and network pharmacology were combined to draw target-metabolite pathways. Apart from that, the targets of associated pathways were confirmed, and the mechanism of action was made clear, using immunohistochemistry. The pharmacodynamic results, including disease activity index (DAI), histological evaluation, and inflammatory cytokines in colon tissues, demonstrated that JE significantly relieved the physiological and pathological symptoms of UC. Network pharmacology analysis indicated 25 core targets, such as TNF, IL-6, PTGS2 and RELA, and four key pathways, including the NF-κB signaling pathway and arachidonic acid metabolism pathway, which were the key connections between JE and UC. Metabolomics analysis identified 45 endogenous differential metabolites and 9 metabolic pathways by enrichment, with the arachidonic acid metabolism pathway being the main metabolism pathway, consistent with the prediction of network pharmacology. IκB, p65 and COX-2 were identified as key targets and this study demonstrated for the first time that JE reverses 2.5% DSS-induced UC in mice via the IκB/p65/COX-2/arachidonic acid pathway. This study reveals the complex mechanisms underlying the therapeutic effects of JE on UC and provides a new approach to identifying the underlying mechanisms of the pharmacological action of Chinese natural medicines such as JE.

Deciphering the mechanisms of Yinlan Tiaozhi capsule in treating hyperlipidemia by combining network pharmacology, molecular docking and experimental verification.

Yinlan Tiaozhi capsule (YLTZC) has been widely used to treat hyperlipidemia (HLP). However, its material basis and underlying pharmacological effects remain unclean. The current study aimed to explore the mechanisms involved in the treatment of YLTZC on HLP based on network pharmacology, molecular docking, and experimental verification. Firstly, UPLC-Q-TOF-MS/MS was used to comprehensively analyze and identify the chemical constituents in YLTZC. A total of 66 compounds, mainly including flavonoids, saponins, coumarins, lactones, organic acids, and limonin were characterized and classified. Simultaneously, the mass fragmentation pattern of different types of representative compounds was further explored. By network pharmacology analysis, naringenin and ferulic acid may be the core constituents. The 52 potential targets of YLTZC, including ALB, IL-6, TNF, and VEGFA, were considered potential therapeutic targets. Molecular docking results showed that the core active constituents of YLTZC (naringenin and ferulic acid) have a strong affinity with the core targets of HLP. Lastly, animal experiments confirmed that naringenin and ferulic acid significantly upregulated the mRNA expression of ALB and downregulated the mRNA expression of IL-6, TNF, and VEGFA. In sum, the constituents of YLTZC, such as naringenin and ferulic acid, might treat HLP by regulating the mechanism of angiogenesis and inhibiting inflammatory responses. Furthermore, our data fills the gap in the material basis of YLTZC.

[Simultaneous determination of six rare sugars in solid foods by high performance liquid chromatography-evaporative light-scattering detection].

Excessive sugar consumption is associated with metabolic health problems. Rare sugars are gradually being used as substitutes for sugar, and their consumption is increasing daily, raising food-safety issues such as false advertising, adulteration, and overdosing. The determination of rare-sugar compounds has attracted considerable attention in recent years. However, no standard method for the simultaneous determination of six rare sugars (allulose, tagatose, trehalose, isomaltulose, erythritol, and mannitol) in solid foods is available. Therefore, establishing a suitable analytical method for these sugars is necessary. In this study, high performance liquid chromatography coupled with evaporative light-scattering detection was used to determine rare sugars in solid foods. The optimum chromatographic and detector conditions were determined by evaluating the instrument parameters. Analysis was carried out on a Zorbax Original NH2 column (250 mm×4.6 mm, 5 µm) via flow-rate gradient elution (0-15 min, 1.0 mL/min; 15-18 min, 1.0-2.0 mL/min; 18-25 min, 2.0 mL/min) with acetonitrile-water (80∶20, v/v) as the mobile phase. Sharp and symmetric chromatographic peaks were obtained under these conditions. The resolutions for all the six rare sugars were greater than 1.5. Optimization of the evaporative light-scattering detector was extremely important to the responses of the rare-sugar compounds. The two most significant parameters were the nebulizer carrier gas flow rate and drift tube temperature. The detection system was operated under the following conditions: the drift tube temperature was set to 50 ℃, the nebulizer carrier gas was high-purity nitrogen, the carrier gas flow rate was 1.0 mL/min, the nitrogen pressure was regulated to 275.79 kPa, and the gain factor was set to 3. The sample was extracted with 25 mL of water, shaken and vortexed for 10 min, purified with 200 µL of zinc acetate solution and 200 µL of potassium ferricyanide solution, and centrifuged at 4500 r/min for 10 min. Next, 1 mL of the supernatant was passed through a 0.22 µm aqueous-phase filter membrane, and the filtrate obtained was analyzed using the evaporative light-scattering detector. The six rare sugars were quantitatively analyzed using the external standard method and showed good linearity with coefficients of determination (R2) greater than 0.9985. The limits of detection and quantification were 0.020-0.60 and 0.60-1.8 g/100 g, respectively. In addition, when blank solid food samples were spiked with the analytes at three levels, the average recoveries of the six rare sugars were 92.6%-103.2%, with relative standard deviations (RSDs) of 0.7%-4.4%. An RSD of <5% indicated that the method had good precision. Interference experiments were performed to determine whether the sugars and artificial sweeteners commonly found in solid foods affected the targets. The method established in this study was used to analyze the contents of the six rare sugars in actual solid food samples. The experimental results showed various levels of rare glycoconjugates in different solid foods. Moreover, the actual compositions and labeled of rare glycoconjugates in the solid foods were generally consistent. The proposed method features simple operation, rapid results, high sensitivity, and good reproducibility; thus, it meets the requirements for the detection of the six rare sugars in solid foods. It also provides technical support for the development of methodological standards and detection limits for rare sugars in Chinese foods. The results of this study are of great relevance for the daily monitoring of the levels of the six rare sugars in solid foods.

Network pharmacology analysis and experimental validation to explore the mechanism of Bushao Tiaozhi capsule (BSTZC) on hyperlipidemia.

Bushao Tiaozhi Capsule (BSTZC) is a novel drug in China that is used in clinical practice and has significant therapeutic effects on hyperlipidemia (HLP). In our previous study, BSTZC has a good regulatory effect on lipid metabolism of HLP rats. However, its bioactive compounds, potential targets, and underlying mechanism remain largely unclear. We extracted the active ingredients and targets in BSTZC from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and literature mining. Subsequently, core ingredients, potential targets, and signaling pathways were determined through bioinformatics analysis, including constructed Drug-Ingredient-Gene symbols-Disease (D-I-G-D), protein-protein interaction (PPI), the Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, the reliability of the core targets was evaluated using in vivo studies. A total of 36 bioactive ingredients and 209 gene targets were identified in BSTZC. The network analysis revealed that quercetin, kaempferol, wogonin, isorhamnetin, baicalein and luteolin may be the core ingredients. The 26 core targets of BSTZC, including IL-6, TNF, VEGFA, and CASP3, were considered potential therapeutic targets. Furthermore, GO and KEGG analyses indicated that the treatment of HLP by BSTZC might be related to lipopolysaccharide, oxidative stress, inflammatory response and cell proliferation, differentiation and apoptosis. The pathway analysis showed enrichment for different pathways like MAPK signaling pathway, AGE-RAGE signaling pathway in diabetic, IL-17 signaling pathway and TNF signaling pathway. In this study, network pharmacology analysis, and experiment verification were combined, and revealed that BSTZC may regulate key inflammatory markers and apoptosis for ameliorating HLP.

The influence of landscape features on road development in a loess region, China.

Many ecologists focus on the effects of roads on landscapes, yet few consider how landscapes affect road systems. In this study, therefore, we quantitatively evaluated how land cover, topography, and building density affected the length density, node density, spatial pattern, and location of roads in Dongzhi Yuan, a typical loess region in China. Landscape factors and roads were mapped using images from SPOT satellite (Système Probatoire d'Observation de la Terre), initiated by the French space agency and a digital elevation model (DEM). Detrended canonical correspondence analysis (DCCA), a useful ordination technique to explain species-environment relations in community ecology, was applied to evaluate the ways in which landscapes may influence roads. The results showed that both farmland area and building density were positively correlated with road variables, whereas gully density and the coefficient of variation (CV of DEM) showed negative correlations. The CV of DEM, farmland area, grassland area, and building density explained variation in node density, length density, and the spatial pattern of roads, whereas gully density and building density explained variation in variables representing road location. In addition, node density, rather than length density, was the primary road variable affected by landscape variables. The results showed that the DCCA was effective in explaining road-landscape relations. Understanding these relations can provide information for landscape managers and transportation planners.

[Study on quality control of herbal material of paeony formula granule by near infrared diffuse reflection spectroscopy].

OBJECTIVE: To develop a novel method to determine fastly and nondestructively the content of paeoniflorin, albiflorin and moisture in Radix Paeoniae Alba with near infrared diffuse reflection spectroscopy. METHOD: Multivariate calibration models based on PLS algorithm were developed to correlate the spectra and the corresponding values determined by the reference method. RESULT: The corelation coefficients (R2) of the calibration models were 0.938, 0.943 and 0.976, and the prediction average relative deviation for paeoniflorin, albiflorin and moisture content were 6.5%, 0.23% and 3.8%, respectively. CONCLUSION: The NIRS determination method is rapid, accurate, nondestructive and non-pollution. It can dispose the samples without complicated pretreatment. It is qualified to analyze rapidly traditional Chinese medicine whose components are complex. NIRS can be used to control the quality of herbal material of paeony formula granule.

Elemental stoichiometry (C, N, P) of soil in the Yellow River Delta nature reserve: Understanding N and P status of soil in the coastal estuary.

The Yellow River Delta Nature Reserve (YNR), which includes two separated regions: part of the old Yellow River Delta (OYD) and part of the current Yellow River Delta (CYD), was established to protect coastal wetlands in the coastal estuary. A total of 120 plots were sampled in the YNR in April 2016, and the spatial patterns of soil C, N and P contents and their stoichiometric ratios (C:N (RCN), C:P (RCP) and N:P (RNP)) were studied and interpolated using the Ordinary Kriging method. Results indicated that the soil elemental contents and stoichiometric ratios showed high spatial heterogeneity and large variations. The mean C:N:P ratio (RCNP) was ~ 64.7:2.3:1 in OYD, and ~ 64.5:2.0:1 in CYD, respectively, and a well-constrained RCP ratio ~ 65:1 was found in the 0-50 cm soil depth within the YNR. N showed greater variation than C and P. Furthermore, N contents in the 0-5 cm soil layer of OYD were significantly higher than that of CYD (F = 4.79, p = 0.03); RCN in 0-5 cm, 5-10 cm layers of OYD was significantly lower than those in the same layers of CYD (F = 4.75, p = 0.03; F = 5.18, p = 0.02, respectively). RNP in 0-5 cm soil layer of OYD was notably higher than that of CYD (F = 4.88, p = 0.03). These results were due to the combined actions of sedimentation, reclamation and fertilization. Finally, we concluded that a longer reclamation and fertilization history led to decreased RCN in coastal estuary soils, confirmed that the soil of the YNR exhibits N limitation, and suggested that the soil RCN and RNP could be good indicators of the anthropogenic improvement status during soil development in this coastal estuary.

Potentially toxic trace element pollution in long-term fertilized agricultural soils in China: A meta-analysis.

Fertilization results in potentially toxic trace element (PTTE) pollution in agricultural soils. However, it is unclear which factors determine the effect sizes of fertilization on PTTEs at the multiple spatial-temporal scale. This work synthesized 379 observations in 78 field sites (3-35 years) across China's main grain producing areas, and showed that long-term organic fertilization significantly enhanced total Cu, Zn and Cd by 25.7%, 18.9% and 66.6%, and soil available Cu, Zn and Cd by 60.5%, 155.3% and 83.6%, respectively; whereas long-term inorganic fertilization increased only available Cu, Zn and Cd by an average of 6.3%. Organic fertilizer (OF) type and application rate dominated the variation of PTTE concentrations, where approximately one-half of Cd pollution (42.6% of total Cd and 47% of available Cd) was observed. Furthermore, OFs containing Cd less than 1 mg kg-1 were recommended to be safely applied to agricultural soils. Soil type was main factor under long-term inorganic fertilization determining available PTTE variation, resulted in higher pollution risk in some soils such as Alfisols and Semi-hydromorphic soils, where we suggested the use of lower amounts of P fertilizers or the application of ones having small amounts of PTTEs. In short, long-term organic fertilization caused serious pollution of PTTEs especially Cd in Chinese croplands, and some strategies with a focus towards reducing the pollution risk must be developed, e.g., promoting straw return, forbidding Cd addition to feeds and feed additives, and improving carbon sequestration efficiency (CSE) of OFs and thus soil organic matter (SOM).