[UPLC-QE-Orbitrap-MS combined with network pharmacology to explore differential components and mechanisms of raw and scorched rhubarb for treatment of ulcerative colitis].

This study compared the therapeutic difference effects of the raw and scorched rhubarb for the treatment of ulcerative colitis(UC) and explored their difference in chemical components and mechanisms by using ultra-high performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry(UPLC-QE-Orbitrap-MS) and network pharmacology. The UC therapeutic effects of Shaoyao Decoction with the raw rhubarb or the scorched rhubarb were evaluated by dextran sulfate sodium(DSS)-induced mouse model. The results showed that Shaoyao Decoction with either the raw rhubarb or the scorched rhubarb could relieve the UC symptoms of mice to different extents, while the scorched rhubarb-based formula showed advantages in reducing hemorrhagic diarrhea and inflammation levels. UPLC-QE-Orbitrap-MS was used to identify a total of 78 small molecules in the water decoction of the raw and scorched rhubarb. Multivariate statistical methods were used to screen components increasing significantly after the scorching process. The seven compounds included five free anthraquinones, gallic acid, and 5-hydroxymethylfurfural(HMF). Meanwhile, the nine compounds decreasing scorching were mainly combined anthraquinones and catechins-related compounds. Network pharmacology and molecular docking suggested that free anthraquinones, gallic acid, and 5-HMF may act on core targets such as B-cell lymphoma-2(BCL2), epidermal growth factor receptor(EGFR), tumor necrosis factor(TNF), and caspase-3(CASP3) and influence the signaling pathways such as phosphoinositide-3-kinase/protein kinase B(PI3K/Akt), hypoxia inducible factor-1(HIF-1), TNF, and mitogen-activated protein kinase(MAPK), so as to regulate the inflammation response, oxidative stress, and cell apoptosis to relieve UC symptoms. This study compared the therapeutic effects and chemical components of the raw and scorched rhubarb, providing the clinical reference for using rhubarb to treat UC.

[Research progress on induced hepatic stellate cell ferroptosis in prevention and treatment of liver fibrosis].

Liver fibrosis is a key pathological stage in the progression of chronic liver disease. If the disease is mistreated, it can further deteriorate into liver failure, which seriously affects the quality of life of patients and brings heavy medical costs. Hepatic stellate cell(HSC) activation triggers extracellular matrix(ECM) deposition, which plays an important driving role in liver fibrosis, and ferroptosis is an effective strategy to clear or reverse the activation of HSCs into a deactivated phenotype. Therefore, inhibiting the activation and proliferation of HSCs by regulating ferroptosis is the key to the treatment of this disease, so as to derive the prospect of inducing ferroptosis of HSCs(including RNA-binding proteins, non-coding RNA, chemicals, and active components of traditional Chinese medicine) to intervene in liver fibrosis. On this basis, this paper started from the activation of HSCs to induce ECM deposition and focused on summarizing the mechanism of inducing HSC ferroptosis in delaying the progression of liver fibrosis, so as to continuously enrich the clinical practice of liver fibrosis and provide a reference for subsequent basic research.

Identification of triple-negative breast cancer and androgen receptor expression based on histogram and texture analysis of dynamic contrast-enhanced MRI.

BACKGROUND: Triple-negative breast cancer (TNBC) is highly malignant and has a poor prognosis due to the lack of effective therapeutic targets. Androgen receptor (AR) has been investigated as a possible therapeutic target. This study quantitatively assessed intratumor heterogeneity by histogram analysis of pharmacokinetic parameters and texture analysis on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to discriminate TNBC from non-triple-negative breast cancer (non-TNBC) and to identify AR expression in TNBC. METHODS: This retrospective study included 99 patients with histopathologically proven breast cancer (TNBC: 36, non-TNBC: 63) who underwent breast DCE-MRI before surgery. The pharmacokinetic parameters of DCE-MRI (Ktrans, Kep and Ve) and their corresponding texture parameters were calculated. The independent t-test, or Mann-Whitney U-test was used to compare quantitative parameters between TNBC and non-TNBC groups, and AR-positive (AR+) and AR-negative (AR-) TNBC groups. The parameters with significant difference between two groups were further involved in logistic regression analysis to build a prediction model for TNBC. The ROC analysis was conducted on each independent parameter and the TNBC predicting model for evaluating the discrimination performance. The area under the ROC curve (AUC), sensitivity and specificity were derived. RESULTS: The binary logistic regression analysis revealed that Kep_Range (p = 0.032) and Ve_SumVariance (p = 0.005) were significantly higher in TNBC than in non-TNBC. The AUC of the combined model for identifying TNBC was 0.735 (p < 0.001) with a cut-off value of 0.268, and its sensitivity and specificity were 88.89% and 52.38%, respectively. The value of Kep_Compactness2 (p = 0.049), Kep_SphericalDisproportion (p = 0.049), and Ve_GlcmEntropy (p = 0.008) were higher in AR + TNBC group than in AR-TNBC group. CONCLUSION: Histogram and texture analysis of breast lesions on DCE-MRI showed potential to identify TNBC, and the specific features can be possible predictors of AR expression, enhancing the ability to individualize the treatment of patients with TNBC.

[Study on serum pharmacodynamic material basis of Gegen Qinlian Decoction in treatment of ulcerative colitis based on UHPLC-Q-Orbitrap-MS].

This study established a mouse model of ulcerative colitis and explored the serum transitional components of Gegen Qinlian Decoction by UHPLC-Q-Orbitrap-MS. Based on the exact relative molecular weight and MS/MS spectrum, 55 prototype components and 59 metabolites were identified from the model group, while 18 prototype components and 35 metabolites from the control group. The prototype components in serum were mainly flavonoids and the characteristic components of the model group were alkaloids. Glucuronidation, sulfonation, and glycosylation have been confirmed to be the main metabolic types in vivo. The results of comparative analysis of differences indicated that puerarin, baicalin, wogonoside, wogonin, chrysin, oroxylin A, berberine, berberrubine, and palmatine were the characteristic components in model state, which at the same time, were confirmed by pharmacological studies to be the serum pharmacodynamic material basis of Gegen Qinlian Decoction in the treatment of ulcerative colitis. This study has provided reference for explaining the metabolic transformation pattern and mechanism of action of Gegen Qinlian Decoction in vivo.

[Compatibility mechanism of Gegen Qinlian Decoction in treatment of ulcerative colitis based on network pharmacology].

Gegen Qinlian Decoction(GQD) is commonly used for the clinical treatment of ulcerative colitis(UC) and other diseases, but its compatibility mechanism has not been elucidated systematically. In this study, the compatibility mechanism of GQD against UC was revealed based on the blood components in the mouse model of UC by network pharmacology. The targets of blood components of GQD were collected to construct a protein-protein interaction(PPI) network. The key targets were screened out according to the topological parameters of the network, and 16 core components were identified, such as puerarin, chrysin, berberine, and liquiritigenin, based on the key targets in the blood components. Functional enrichment analysis was performed on the key targets, and the regulatory network of the prescription was constructed, which elucidated the compatibility mechanism of the Chinese herbal drugs in the prescription at both target and pathway levels. The results showed that all the Chinese herbal drugs in GQD had heat-clearing and toxin-removing effects, and the four Chinese herbal drugs synergistically exerted their effects by co-regulating protooncogenes, such as FOS and JUN, and characteristically regulating signal transducer and activator of transcription 3(STAT3) and interleukin-6(IL-6). The pathway analysis revealed that GQD exerted heat-clearing and toxin-removing effects mainly by regulating the inflammatory response-related signaling pathways, such as Toll-like receptor, tumor necrosis factor(TNF), and mitogen-activated protein kinase(MAPK). Furthermore, the study revealed the synergistic effects of Chinese herbal drugs in GQD based on the TNF signaling pathway. The results showed that the sovereign drug Puerariae Lobatae Radix played a primary role in the regulation of targets in the TNF signaling pathway, the minister drugs Scutellariae Radix and Coptidis Rhizoma showed the synergistic effects with Puerariae Lobatae Radix, and the assistant and guiding drug Glycyrrhizae Radix et Rhizoma supported Puerariae Lobatae Radix in the key target NF-κB and the process of cell adhesion. The drugs in GQD showed good characteristics of compatibility in the TNF signaling pathway. This study is expected to provide the basis for the further exploration of the compatibility mechanism of GQD.

[Quality evaluation of commercial Ginseng Radix et Rhizoma Rubra based on multi-component quantitative analysis].

To comprehensively evaluate the quality of commercial Ginseng Radix et Rhizoma Rubra, 43 batches of commercial Ginseng Radix et Rhizoma Rubra were collected to determine the content of nine ginsenosides Rg_1, Re, Rb_1, Rk_3, Rh_4, 20(S)-Rg_3, 20(R)-Rg_3, Rk_1, and Rg_5 by high performance liquid chromatography(HPLC). The quality of the commercial Ginseng Radix et Rhizoma Rubra was evaluated by correlation analysis, principal component analysis, factor analysis, analysis of variance(ANOVA), and cluster heatmap analysis. The content determination indicated that the content of common ginsenosides in commercial Ginseng Radix et Rhizoma Rubra were higher while that of rare ginsenosides were lower. Multivariate statistical analysis revealed that ginsenosides Rg_1 and Rb_1 were significantly positively correlated with rare ginsenosides, and Rg_1, Rb_1 and rare ginsenosides played an important role in evaluating the quality of commercial Ginseng Radix et Rhizoma Rubra. In combination with the processing principle and current quality situation of Ginseng Radix et Rhizoma Rubra, it is recommended to improve the content limit of Rb_1 in the existing quality standards.

Store-operated calcium entry-associated regulatory factor regulates airway inflammation and airway remodeling in asthma mice models.

Store-operated calcium entry (SOCE) is involved in the pathogenesis of airway inflammation and remodeling in asthma. Store-operated calcium entry-associated regulatory factor (SARAF) can downregulate SOCE. We sought to investigate the role of SARAF in the regulation of airway inflammation and remodeling in asthma mice models, as well as in the functional regulation of human airway smooth muscle cells (hASMCs). Balb/c mice were sensitized and challenged with ovalbumin to establish the asthma mice models. Mice were transfected with lentivirus, which expressed the SARAF gene + GFP (green fluorescence protein) or the negative control gene + GFP. Airway resistance was measured with the animal pulmonary function system. Airway inflammation and remodeling were evaluated via histological staining. In vitro cultured hASMCs were transfected with scrambled small interfering RNA (siRNA) or SARAF-specific siRNA, respectively. The proliferation, migration rate, hypertrophy, and SOCE activity of hASMCs were examined with Cell Counting Kit-8, wound healing test, bright field imaging, and Ca2+ fluorescence imaging, respectively. SARAF expression was measured by quantitative real-time PCR. Asthma mice models showed decreased SARAF mRNA expression in the lungs. SARAF overexpression attenuated airway inflammation, resistance, and also remodeling. Downregulation of SARAF expression with siRNA promoted the proliferation, migration, hypertrophy, and SOCE activity in hASMCs. SARAF plays a protective role against airway inflammation and remodeling in asthma mice models by blunting SOCE; SARAF may also be a functional regulating factor of hASMCs.

Exploring the Coordination Modes of a Keggin-Type [ZnW12O40]6- Anionic Cluster: Bonding Patterns, Crystal Structure, and Semiconducting Properties.

Polyoxometalate-based organic-inorganic hybrid compounds (POIHCs) have been greatly developed due to their wide application prospects, but the pursuit of their directed synthesis via molecular design still remains a challenge. Herein, we demonstrate that the coordination modes of the Keggin-type [ZnW12O40]6- anion can be tuned, which leads to different semiconductor characteristics. Using the same building block, ligand, and metal ion (ZnW12, phen, Cu2+), we synthesized three new POIHCs with different bonding patterns by means of different coordination modes of ZnW12. The three POIHCs (H2phen){ZnW12O40[Cu(phen)2]2}·3H2O (1), {ZnW12O40[Cu(phen)(H2O)2]2[Cu(phen)(H2O)]}n·3H2O (2), and (Me4N)2{ZnW12O40[Cu(phen)(H2O)]2}n·5H2O (3) (phen = 1,10-phenanthroline) have been structurally characterized by single-crystal X-ray diffraction. Compound 1 appears as a zero-dimensional coordination complex cluster, while compounds 2 and 3 are both 1D chain structures with different Cu2+ bridge linkages. Although these three POIHCs possess the same chemical components, their semiconductor properties are different, which is demonstrated by measurements of transient photocurrent and band gap (Eg) values. Furthermore, we carried out comparative experiments on the photoconductivity performance of compounds 1-3 and their photocatalytic reduction from O2 to H2O2, indicating the significant influence of the energy level matching on the photocatalytic activity.

Transcriptomic analyses reveal antiinflammatory mechanism of withanolides derived from the fruits of Physalis alkekengi L. var. franchetii.

In China, the fruits of Physalis alkekengi L. var. franchetii, which are conventionally utilized as edible berry, have attracted wide attention due to its significant biological activities. In the present study, phytochemical studies on the fruits of Physalis plants afforded six compounds, including two new withanolides (1-2) and four known agnologues (3-6). The inhibitory effects of these compounds on the formation of nitric oxide (NO) stimulated by lipopolysaccharide (LPS) in RAW264.7 macrophages were evaluated. Physapubescin M (1), with IC50 value of 1.58 µM, was selected for further study. The protein expression of COX-2 and iNOS, and LPS-induced production of cytokines (IL-6, IL-1ß and TNF-α) were reduced by physapubescin M (1) in a dose-dependent way. In addition, transcriptomic analyses were conducted to profile gene expression alterations in LPS-induced RAW264.7 cells upon treatment of physapubescin M (1) and the potential antiinflammatory mechanism of withnolides was mentioned. These results provide broad view to the underlying antiinflammatory mechanism of withnolides, and give a theoretical basis for the utilization of the fruits of P. alkekengi L. var. franchetii.

[Molecular mechanism of Qishen Yiqi Dripping Pills in treating myocardial ischemia:a study based on HIF-1 signaling pathway].

Qishen Yiqi Dripping Pills(QSYQ) are used clinically to treat various myocardial ischemic diseases, such as angina pectoris, myocardial infarction, and heart failure; however, the molecular mechanism of QSYQ remains unclear, and the scientific connotation of traditional Chinese medicine(TCM) compatibility has not been systematically explained. The present study attempted to screen the critical pathway of QSYQ in the treatment of myocardial ischemia by network pharmacology and verify the therapeutic efficacy with the oxygen-glucose deprivation(OGD) model, in order to reveal the molecular mechanism of QSYQ based on the critical pathway. The key targets of QSYQ were determined by active ingredient identification and target prediction, and underwent pathway enrichment analysis and functional annotation with David database to reveal the biological role and the critical pathway of QSYQ. Cell counting Kit-8(CCK-8), lactate dehydrogenase(LDH), and Western blot tests were launched on high-content active ingredients with OGD cell model to reveal the molecular mechanism of QSYQ based on the critical pathway. The results of network pharmacology indicated that QSYQ, containing 18 active ingredients and 82 key targets, could protect cardiomyocytes by regulating biological functions, such as nitric oxide biosynthesis, apoptosis, inflammation, and angiogenesis, through TNF signaling pathway, HIF-1 signaling pathway, PI3 K-Akt signaling pathway, etc. HIF-1 signaling pathway was the critical pathway. As revealed by CCK-8 and LDH tests, astragaloside Ⅳ, salvianic acid A, and ginsenoside Rg_1 in QSYQ could enhance cell viability and reduce LDH in the cell supernatant in a concentration-dependent manner(P<0.05). As demonstrated by the Western blot test, astragaloside Ⅳ significantly down-regulated the protein expression of serine/threonine-protein kinase(Akt1) and hypoxia-inducible factor 1α(HIF-1α) in the HIF-1 signaling pathway, and up-regulated the protein expression of vascular endothelial growth factor A(VEGFA). Salvianic acid A significantly down-regulated the protein expression of upstream phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3 CA) and downstream HIF-1α of Akt1. Ginsenoside Rg_1 significantly down-regulated the expression of HIF-1α protein and up-regulated the expression of VEGFA. The therapeutic efficacy of QSYQ on myocardial ischemia was achieved by multiple targets and multiple pathways, with the HIF-1 signaling pathway serving as the critical one. The active ingredients of QSYQ could protect cardiomyocytes synergistically by regulating the targets in the HIF-1 signaling pathway to inhibit its expression.

[The Clinical Value of PNI in Assessing the Prognosis of Small Cell Lung Cancer].

OBJECTIVE: To evaluate the clinical value of prognostic nutritional index (PNI) in assessing the prognosis of small cell lung cancer (SCLC) patients. METHODS: The clinical data of SCLC patients who were initial diagnosed by pathology and conformed to the conditions of this study from January 2017 to January 2018 were retrospectively collected. The PNI values were calculated and divided into high PNI and low PNI groups according to the median value. The potential prognostic factors for SCLC patients were analyzed. RESULTS: One hundred and five patients were divided into high-PNI and low-PNI groups according to the PNI median (48.68). The median survival time was 25.1 months and 14.2 months respectively. The one-year survival rates were 82.5% and 65.3% respectively and the two-year survival rates were 49.7% and 28.4% respectively, the differences were all statistically significant ( P<0.05). Univariate analysis showed that gender, ECOG PS score, clinical stage and PNI were correlated with overall survival (OS) ( P<0.05). Multivariate analysis showed that PNI (odds ratio ( OR)=0.331，95% confidence interval: 0.189-0.580) and gender ( OR=1.897，95% confidence interval: 1.051-3.423) were independent prognostic factors for SCLC patients. CONCLUSION: Low PNI patients generally symbolize poor prognosis, PNI calculation is simple and easy to obtain, worthy of clinical promotion.

[Inhibitory effect of wogonin on human colorectal cancer cell SW480 based on network pharmacology].

Wogonin is a main effective component of Scutellaria baicalensis, with a significant anti-cancer activity. Recently, extensive studies focused on anti-cancer pharmacological effects of wogonin, but there were still a few studies on its molecular mechanism. Therefore, the molecular targets of its anti-cancer activity were still unclear. In this study, network pharmacology was applied to investigate the potential targets and molecular pathway of wogonin in inhibiting the growth of colorectal cancer. It indicated that Wnt/ß-catenin was a key pathway of wogonin on colorectal cancer. Then, pharmacology and molecular mechanism studies were performed according to network pharmacological results. Pharmacological results revealed that wogonin inhibited significantly the proliferation of SW480(P<0.001), with a concentration-dependent regularity in the range of 12.5-50 µmol·L~(-1). Additionally, wogonin could induce G_1 phase blocking of SW480 cells. Western blot was used to investigate the effect of wogonin on four characteristic proteins of Wnt/ß-catenin pathway. CTNNB1(ß-catenin), BIRC5(survivin) and GSK3 B were down-regulated significantly, while the expression level of BAX was up-regulated(P<0.05). In conclusion, wogonin could inhibit the proliferation of SW480 cells through Wnt/ß-catenin pathway. The feature protein CTNNB1(ß-catenin), BIRC5(survivin), GSK3 B and BAX were identified as the potential targets. This study illuminated the anti-cancer molecular mechanism and drug targets of wogonin, which provided a theoretical basis for anti-colon cancer drug discovery and clinical application.

Analysis of risk factors for cervical lymph node metastasis of papillary thyroid microcarcinoma: a study of 268 patients.

BACKGROUND: To investigate the risk factors of cervical lymph node (LN) metastasis in papillary thyroid microcarcinoma (PTMC) patients. METHODS: We retrospectively analyzed the clinicopathologic data of all patients who received standard lobectomy for PTMC at our institution between October 2017 and January 2019. Central LNs were dissected in all patients. Lateral LNs were dissected if metastasis to the lateral LNs was suggested based on pre-op fine-needle aspiration biopsy. The relationship between variables available prior to surgery and cervical LN metastasis was examined using multivariate regression. RESULTS: Post-op pathologic examination revealed cervical LN metastasis in 79 (29.5%) patients. Seventy subjects had metastasis only to central LNs, and 4 (1.5%) patients had metastasis only to lateral LNs. Five patients had metastasis to both central and lateral LNs. In comparison to patients without cervical LN metastasis, those with LN metastasis were significantly younger (40.63 ± 13.07 vs. 44.52 ± 12.23 years; P = 0.021) and had significantly larger tumor diameter on pathology (6.7 ± 2.2 vs. 5.9 ± 2.4 mm; P = 0.010). Multivariate regression analysis identified the following independent risks for cervical LN metastasis: male sex (OR 2.362, 95%CI 1.261~4.425; P = 0.007), age (OR 0.977, 95%CI 0.956~0.999; P = 0.042) and ultrasound tumor diameter at > 5 mm (OR 3.172, 95%CI 1.389~7.240; P = 0.006). CONCLUSION: Cervical LN metastasis occurs in a non-insignificant proportion of PTMC patients. Independent risks included male sex, younger age and larger tumor diameter on ultrasound.

[Research and development thought on biopharmaceutics classification system of Chinese materia medica].

The biopharmaceutics classification system( BCS) is a scientific framework or method for classifying drugs based on drug solubility and permeability,which can be used to provide drug bioavailability-absorption correlation analysis. Based on the characteristics of multi-component and multi-target of traditional Chinese medicine( TCM) as well as the concept,method and technology of BCS,the research group proposed biopharmaceutics classification system of Chinese materia medica( CMMBCS) and carried out research and data accumulation of classical prescriptions. Based on the previous research results,further development ideas under the CMMBCS concept and framework were further proposed in this study. In the course of research,the influence of the intermediate links of the complex interactions of the multi-component environment was omitted,and the component absorption studies on the main clinical effects of prescription ingredients were directly concerned,or the components and data were reversely extracted from the aspects of metabolism,pharmacodynamic pathways and absorption principles. Studies were conducted from two aspects( single component and compound prescription) to comprehensively evaluate the absorption properties of TCM compound. In the research path,the different ways in which Chinese medicine could exert its efficacy were fully considered,and CMMBCS classification and establishment rules were clarified mainly by focusing on the absorption pathway into the blood. Specifically,the network pharmacology and molecular docking technology were used to screen the compound index components of TCM; the absorption rules were studied by the physiologically based pharmacokinetic models and the absorption parameters of CMMBCS were calculated by reverse reasoning. Then the CMMBCS classification of TCM prescription was corrected by studying the efficacy or absorption pathway. In this paper,the theoretical framework and research methodology of CMMBCS were systematically improved based on the establishment of CMMBCS basic theory,the supplementary of drug-oriented research ideas and the application of modern mature Chinese medicine methodology.

[Simultaneous quantification and consistency analysis of 19 representative components in Longshengzhi Capsules by HPLC-QQQ/MS].

Longshengzhi capsule consisting of 12 herbs is widely used in clinically treating cerebral ischemia during recovery period.In this study,in order to investigate the consistency of different batches of Longshengzhi capsules,a high performance liquid chromatography coupled to triple quadrupole mass spectrometry method(HPLC-QQQ/MS) was developed for the determination of 19 representative components in Longshengzhi Capsules within 9 min. Methodology validation indicated this method was simple,rapid,accurate,highly sensitive and reproducible,and it could be used for the content determination of components in Longshengzhi Capsules. The consistency analysis results showed that paeoniflorin and calycosin-7-glucoside in Longshengzhi Capsules had the highest content; RSD value of total content of 19 compounds was 5. 2% and the RSD value of main compounds such as astragaloside and calycosin-7-glucoside was all less than 15%,reflecting good consistency among different batches. This study has provided a scientific method and basis for the quality control and consistency evaluation of Longshengzhi Capsules.

Pure mechanistic analysis of additive neuroprotective effects between baicalin and jasminoidin in ischemic stroke mice.

Both baicalin (BA) and jasminoidin (JA) are active ingredients in Chinese herb medicine Scutellaria baicalensis and Fructus gardeniae, respectively. They have been shown to exert additive neuroprotective action in ischemic stroke models. In this study we used transcriptome analysis to explore the pure therapeutic mechanisms of BA, JA and their combination (BJ) contributing to phenotype variation and reversal of pathological processes. Mice with middle cerebral artery obstruction were treated with BA, JA, their combination (BJ), or concha margaritifera (CM). Cerebral infarct volume was examined to determine the effect of these compounds on phenotype. Using the hippocampus microarray and ingenuity pathway analysis (IPA) software, we exacted the differentially expressed genes, networks, pathways, and functions in positive-phenotype groups (BA, JA and BJ) by comparing with the negative-phenotype group (CM). In the BA, JA, and BJ groups, a total of 7, 4, and 11 specific target molecules, 1, 1, and 4 networks, 51, 59, and 18 canonical pathways and 70, 53, and 64 biological functions, respectively, were identified. Pure therapeutic mechanisms of BA and JA were mainly overlapped in specific target molecules, functions and pathways, which were related to the nervous system, inflammation and immune response. The specific mechanisms of BA and JA were associated with apoptosis and cancer-related signaling and endocrine and hormone regulation, respectively. In the BJ group, novel target profiles distinct from mono-therapies were revealed, including 11 specific target molecules, 10 functions, and 10 pathways, the majority of which were related to a virus-mediated immune response. The pure additive effects between BA and JA were based on enhanced action in virus-mediated immune response. This pure mechanistic analysis may provide a clearer outline of the target profiles of multi-target compounds and combination therapies.

Rhynchophylla total alkaloid rescues autophagy, decreases oxidative stress and improves endothelial vasodilation in spontaneous hypertensive rats.

Autophagy plays an important role in alleviating oxidative stress and stabilizing atherosclerotic plaques. However, the potential role of autophagy in endothelial vasodilation function has rarely been studied. This study aimed to investigate whether rhynchophylla total alkaloid (RTA) has a positive role in enhancing autophagy through decreasing oxidative stress, and improving endothelial vasodilation. In oxidized low-density lipoprotein (ox-LDL)-treated human umbilical vein endothelial cells (HUVECs), RTA (200 mg/L) significantly suppressed ox-LDL-induced oxidative stress through rescuing autophagy, and decreased cell apoptosis. In spontaneous hypertensive rats (SHR), administration of RTA (50 mg·kg-1·d-1, ip, for 6 weeks) improved endothelin-dependent vasodilation of thoracic aorta rings. Furthermore, RTA administration significantly increased the antioxidant capacity and alleviated oxidative stress through enhancing autophagy in SHR. In ox-LDL-treated HUVECs, we found that the promotion of autophagy by RTA resulted in activation of the AMP-activated protein kinase (AMPK) signaling pathway. Our results show that RTA treatment rescues the ox-LDL-induced autophagy impairment in HUVECs and improves endothelium-dependent vasodilation function in SHR.

[Studies on constituents of Polygonum multiflorum extract in vivo and in vitro based on UPLC-Q-TOF-MS].

To explore the drug-induced constituents in vivo of Polygonum multiflorum extract (PM). This study was the first to study the drug-induced constituents in target organ liver. Agilent MassHunter qualitative analysis software and Metabolite ID software were applied for the analysis of retention time, exact relative molecular mass, primary and secondary mass spectrum information based on ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and targeted-MS/MS. By comparison with literature and standards, a total of 5 prototypes and 6 metabolites were identified or tentatively elucidated from the liver samples. In addition, the drug-induced constituents in plasma and PM were also analyzed in this study and 8 prototypes and 19 metabolites were detected from the plasma samples, while 30 compounds were detected from the extract of PM. Emodin oxidative acetylation metabolites, hydroxyl methylation metabolites, carboxylation glucuronidation metabolites and ketone glucuronidation metabolites in this study were first reported. Through the comparative analysis between the in vivo and in vitro constituents of PM, the study preliminarily revealed the drug-induced constituents (prototypes and metabolites) in liver and clarified the transfer process and transmutation rules of constituents in PM, blood and liver, which would further deepen our understanding on constituents of PM in vivo.

Detection of trapped charges in the blend films of polystyrene/SFDBAO electrets by electrostatic and Kelvin probe force microscopy.

The charge trapping properties of the blend of polystyrene (PS) and a sterically hindered organic semiconductor SFDBAO (spiro[fluorene-9,7-dibenzo[c,h]acridin-5-one]) are investigated by electrostatic and Kelvin probe force microscopy (EFM and KPFM). EFM signals of trapped charge spots injected with controllable tip biases, which are recorded with different dissipation times t, the percent of SFDBAO in blends, and the scanning tip bias, have been measured. By the quantitative analysis, the excellent trapped charge density of PS/SFDBAO blend films for the holes (∼×10(-5) C m(-2)) is much higher than that of the SFDBAO film (∼×10(-6) C m(-2)) and the PS film (∼×10(-7) C m(-2)). However, the trapped charge density of electrons (∼×10(-7) C m(-2)) has the same order magnitude for SFDBAO, PS and the blend films. The results indicate that the blend of PS and SFDBAO enhances the high-density storage and retention abilities of the holes to a larger extent, but the endurance improvement of the electrons is not that obvious. By the KPFM measurement, we further verify the different diffusion rates of the trapped holes and electrons in the PS/SFDBAO blend films, and discuss the possible physical mechanism. The qualitative and quantitative determination of charge trapping properties in this work can be very useful for the characterization of PS/SFDBAO based charge trapping memory devices.

Coupled effects of local movement and global interaction on contagion.

By incorporating segregated spatial domain and individual-based linkage into the SIS (susceptible-infected-susceptible) model, we propose a generalized epidemic model which can change from the territorial epidemic model to the networked epidemic model. The role of the individual-based linkage between different spatial domains is investigated. As we adjust the timescale parameter τ from 0 to unity, which represents the degree of activation of the individual-based linkage, three regions are found. Within the region of 0 < τ < 0.02 , the epidemic is determined by local movement and is sensitive to the timescale τ . Within the region of 0.02 < τ < 0.5 , the epidemic is insensitive to the timescale τ . Within the region of 0.5 < τ < 1 , the outbreak of the epidemic is determined by the structure of the individual-based linkage. As we keep an eye on the first region, the role of activating the individual-based linkage in the present model is similar to the role of the shortcuts in the two-dimensional small world network. Only activating a small number of the individual-based linkage can prompt the outbreak of the epidemic globally. The role of narrowing segregated spatial domain and reducing mobility in epidemic control is checked. These two measures are found to be conducive to curbing the spread of infectious disease only when the global interaction is suppressed. A log-log relation between the change in the number of infected individuals and the timescale τ is found. By calculating the epidemic threshold and the mean first encounter time, we heuristically analyze the microscopic characteristics of the propagation of the epidemic in the present model.