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This study using traditional Chinese medicine inheritance support software(TCMISS) to analyze the prescription rules of Tibetan medicine containing Terminalia chebula in the Encyclopedia of Chinese Medicine-Tibetan Medicine, Tibetan Medicine Composition Preparation of Modern Research and Clinical Application and Common Interpretation of Tibetan Medicine and so on. TCMISS(V2.5) was used to build a prescription database of Tibetan medicine containing T. chebula.The software statistical statement module, association rules and improved mutual information method and other data mining technologies were adopted to analyze the common herbs, combination rules and core combination of prescriptions containing T. chebula.Total 502 prescriptions containing T. chebula were analyzed and 14 common herbal combinations were summarized, whose ingredients mostly had the functions of clearing heat and detoxicating, promoting blood circulation and stopping pain, warming the middle-jiao and promoting the circulation of Qi. Prescriptions containing T. chebula were commonly used to treat 640 kinds of diseases, there are 22 kinds with high frequency(≥12) in which the representative "Tripa" disease, antiquated febrile symptoms, food poisoning had the highest frequency.T. chebula had different therapeutic effects through different compatibility.The complex composing and medication regularities of Tibetan medicine containing T. chebula have been clarified by TCMISS. That will provide reference for the clinical application of T. chebula and the new development.

Optimized on-line HPLC-DPPH method for evaluation and identification of the antioxidants in <b>Limonium aureum</b> (Linn.)<br><br>Display Omitted<br>• On-line HPLC-DPPH method was used for evaluate and identify of the antioxidants in <b>Limonium aureum</b> (Linn.) extract. • The optimum conditions of the method were obtained by response surface methodology. • Antioxidants were identified by MS.<br><b>Limonium aureum</b> (Linn.) is a traditional Chinese medicine with strong antioxidant activity. To search for antioxidants in <b>L. aureum</b>, an optimized, on-line high performance liquid chromatography (HPLC) method with DPPH (1,1-diphenyl-2-picrylhydrazyl) for the detection of radical scavenging ability was developed. Response surface methodology (RSM) was used to determine the best combination of experimental conditions, such as DPPH concentration, DPPH velocity and the reaction tank length. The optimized method uses a DPPH concentration of 25.0 μg/mL, DPPH velocity of 0.45 mL/min and a 15.0 m long reaction tank. The highly sensitive, optimized method can not only be used for the detection of antioxidants in plants, but can also be coupled with mass spectrometry (MS) to obtain the mass-to-charge ratios of chemical species corresponding to the different peaks in the HPLC profiles. Seven antioxidants were identified in <b>L. aureum</b> using the optimized method, including myricetin-3-<b>O</b>-β-d-(6”-<b>O</b>-galloyl)-glucopyranoside, myricetin-3-<b>O</b>-glucoside, myricitrin, eriodictyol-7-<b>O</b>-glucoside, myricetin, eriodictyol and homoeridictyol.

Studies have revealed that bullying victimization was a risk factor for symptoms of depression, however, less is known about the underlying processes that may mediate or moderate this relationship. This study examined the mediating effect of resilience and moderating effect of mindfulness in the relation between bullying victimization and symptoms of depression. 448 Chinese children in grade 3 to grade 6 were recruited to complete the revised Bully/Victim Questionnaire, the Chinese version of Center for Epidemiologic Studies Depression Scale for Children, the Child and Youth Resilience Measure, as well as the Child and Adolescent Mindfulness Measure. Results showed that resilience partially mediated the relation between bullying victimization and depressive symptoms. Besides, both the effect of bullying victimization on depressive symptoms and the mediating effect of resilience were moderated by mindfulness, and both of the two effects were stronger for children with low mindfulness. The present study can contribute to a better understanding of how and when bullying victimization increases the risk of depression. It suggests that early intervention concerning diminishing negative effects of bullying victimization may start with increasing individual resilience and mindfulness.

AIM: Targeting the VEGF/VEGF receptor (VEGFR) pathway has proved to be an effective antiangiogenic approach for cancer treatment. Here, we identified 6-((2-((3-acetamidophenyl)amino)pyrimidin-4-yl)oxy)-N-phenyl-1-naphthamide (designated herein as DW10075) as a novel and highly selective inhibitor of VEGFRs. METHODS: In vitro tyrosine kinase activity was measured using ELISA, and intracellular signaling pathway proteins were detected by Western blot analysis. Endothelial cell proliferation was examined with CCK-8 assays, and tumor cell proliferation was determined with SRB assays. Cell migration, tube formation and rat aortic ring assays were used to detect antiangiogenic activity. Antitumor efficacy was further evaluated in U87-MG human glioblastoma xenograft tumors in nude mice receiving DW10075 (500 mg · kg(-1) · d(-1), po) for two weeks. RESULTS: Among a panel of 21 kinases tested, DW10075 selectively inhibited VEGFR-1, VEGFR-2 and VEGFR-3 (the IC50 values were 6.4, 0.69 and 5.5 nmol/L, respectively), but did not affect 18 other kinases including FGFR and PDGFR at 10 μmol/L. DW10075 significantly blocked VEGF-induced activation of VEGFR and its downstream signaling transduction in primary human umbilical vein endothelial cells (HUVECs), thus inhibited VEGF-induced HUVEC proliferation. DW10075 (1-100 nmol/L) dose-dependently inhibited VEGF-induced HUVEC migration and tube formation and suppressed angiogenesis in both the rat aortic ring model and the chicken chorioallantoic membrane model. Furthermore, DW10075 exhibited anti-proliferative activity against 22 different human cancer cell lines with IC50 values ranging from 2.2 μmol/L (for U87-MG human glioblastoma cells) to 22.2 μmol/L (for A375 melanoma cells). In U87-MG xenograft tumors in nude mice, oral administration of DW10075 significantly suppressed tumor growth, and reduced the expression of CD31 and Ki67 in the tumor tissues. CONCLUSION: DW10075 is a potent and highly selective inhibitor of VEGFR that deserves further development.

ETHNOPHARMACOLOGICAL RELEVANCE: In Chinese folk medicine, the flower of Edgeworthia gardneri (Wall.) Meisn. is used to treat various metabolic diseases, such as hyperglycemia, hypertension, and hyperlipidemia. AIM OF THE STUDY: This study aimed to explore the antidiabetes potential of the flower of E. gardneri and investigate whether it can benefit the entire gut bacteria community. MATERIALS AND METHODS: Chemical constituents of the extract were analyzed by UHPLC-Q Exactive Mass Spectrometer (UHPLC-QE-MS). The antidiabetes effect of the water extract (WAE) of the flower of E. gardneri was evaluated in diabetic mice induced by high-fat diet (HFD) and streptozotocin (STZ) (six groups, n = 8) daily at doses of 1, 2, and 3 g/kg for 4 weeks. The gut microbiota was analyzed using high-throughput 16S rRNA gene sequencing. Short-chain fatty acids (SCFAs) in the fecal were also investigated. RESULTS: UHPLC-QE-MS analysis identified 29 compounds, including five alkaloids, six coumarins, four flavonoids, 11 organic acids, and three additional compounds, in the WAE. Results showed that the high dose of WAE considerably decreased the blood glucose level by 30.0%. Furthermore, E. gardneri significantly ameliorated insulin resistance and lipid metabolism dysfunction and repaired islet, hepatic, and white fat and colon histology in diabetic mice. Diabetic mice treated with WAE showed apparent changes in the structure and composition of the gut microbiota. WAE reversed the changes in Clostridiales, Lachnospiraceae, S24-7, Rikenellaceae, and Dorea in diabetic mice. The correlation analysis indicated that key OTUs were related to diabetes indices. The amounts of SCFAs, including acetic, propionic, and valeric acids, were significantly high in WAE-treated diabetic groups. CONCLUSIONS: E. gardneri treatment improved the glucose metabolism and reshaped the unbalanced gut microbiota of diabetic mice. Our study provides evidence for application of E. gardneri to treatment of diabetes mellitus.

* Mindful learning is applied into the domain of environmental protection. * We test the association between mindful learning and pro-environmental behavior in the perspective of self-expansion. * Mindful learning could influence self-reported pro-environmental behavioral intentions in both positive and negative ways. * The mindful-leaning material need to be carefully selected and employed.; This current article explores the differential effects of mindful learning on pro-environmental behavior from the perspective of self-expansion. A total of 253 participants were recruited for four experiments. In Study 1, the mindful-learning group reported greater levels of pro-environmental behavioral intentions compared to a randomized control. In Study 2, we utilized different learning materials focusing on self, humans, or the biosphere in three sub-experiments. Study 2a manipulated mindsets by a self-related focus and revealed participants in a mindfulness condition had lower pro-environmental behavioral intentions than those in the mindlessness group. Study 2b centered on humans and results showed that participants in a mindfulness group reported higher levels of pro-environmental behavioral intentions. Finally, Study 2c induced mindsets with a biospheric focus, showing participants in the mindful-learning condition had greater pro-environmental behavioral intentions. Combined, the studies provide empirical evidence that mindful learning could influence self-reported pro-environmental behavioral intentions both positively and negatively.

* Mindful learning is applied into the domain of environmental protection. * We test the association between mindful learning and pro-environmental behavior in the perspective of self-expansion. * Mindful learning could influence self-reported pro-environmental behavioral intentions in both positive and negative ways. * The mindful-leaning material need to be carefully selected and employed.; This current article explores the differential effects of mindful learning on pro-environmental behavior from the perspective of self-expansion. A total of 253 participants were recruited for four experiments. In Study 1, the mindful-learning group reported greater levels of pro-environmental behavioral intentions compared to a randomized control. In Study 2, we utilized different learning materials focusing on self, humans, or the biosphere in three sub-experiments. Study 2a manipulated mindsets by a self-related focus and revealed participants in a mindfulness condition had lower pro-environmental behavioral intentions than those in the mindlessness group. Study 2b centered on humans and results showed that participants in a mindfulness group reported higher levels of pro-environmental behavioral intentions. Finally, Study 2c induced mindsets with a biospheric focus, showing participants in the mindful-learning condition had greater pro-environmental behavioral intentions. Combined, the studies provide empirical evidence that mindful learning could influence self-reported pro-environmental behavioral intentions both positively and negatively.

Methylmercury (MeHg+) is an extremely toxic organomercury cation that can induce severe neurological damage. Once it enters the body, methylmercury binds to amino acids or proteins containing free sulfhydryl groups. In particular, methylmercury is known to bind with human serum albumin (HSA) in human plasma; however, the effects of methylmercury-HSA conjugate (MeHg-HSA) on the central nervous system (CNS) are not fully understood. In the present study, we used the microglial cell line N9 as the target cells to evaluate the effect of MeHg-HSA on physiological function of the CNS preliminarily. The various factors in the cell culture were monitored by MTT assay, total lactate dehydrogenase assay, ELISA, qPCR, Western blot and flow cytometry techniques. The results showed that low-dose treatment with MeHg-HSA activated N9 cells, promoting cell proliferation and total cell number, enhancing NO and intracellular Ca2+ levels, and suppressing the release of TNFα and IL1β without cytotoxic effects; while high-dose MeHg-HSA exhibited cytotoxic effects on N9 cells, including promoting cell death and increasing the secretion of TNFα and IL1β. These results indicate that MeHg-HSA causes hormesis in microglia N9 cells. Furthermore, ERK/MAPKs and STAT3 signaling pathways related to the hormesis of MeHg-HSA on N9 cells. In addition, low dose of MeHg-HSA might be viewed as something very close to a lowest observed adverse effect level (LOAEL) for N9 cells. These findings will be useful for investigating the hormesis mechanism of MeHg+ and exploring the specific functions of MeHg-sulfhydryl conjugates on the central nervous system.

The changes of the immune function of rheumatoid arthritis before and after the Tibetan medicated-bath was observed. It showed a higher level of the rheumatoid factor (RF) titre, immunoglobulin (Ig) G, M, A and CD4 cells, but the CD8 cells was obviously lower before the treatment. Clinical data indicated that the medicated-bath had significant effective rate. In order to elucidate the mechanism of the medicated-bath upon rheumatoid arthritis the RF titre, Ig level, complement C3, 3H-TdR incorporated with lymphocytes transformation and CD3, CD4, CD8 cell level were assayed. Results showed that RF titre decreased after the bath and the negative transforming rate reached 70.6%, Ig level obviously dropped as well as the number of CD4 cells while CD8 cell level increased. The transforming stimulation index of lymphocyte cells obviously decreased. All of the above mentioned showed that there was a higher concentration of the enhancing factor of interleukin-2 (IL2-EF) involved in lymphocyte culture of rheumatoid arthritis patients. They suggested that the Tibetan medicated-bath had an immunomodulating effect on rheumatoid arthritis patients through increasing the level of CD8 cells and reducing CD4 cells.

Environmental problems have attracted increasing attention, yet individuals’ connectedness to nature remains a significant concern for potential solutions to these problems. In this article, we propose a novel method to promote connectedness to nature: mindful learning. One hundred and thirty-four students participated in the experiment. First, baseline measurements using the Connectedness to Nature Scale were obtained. Participants were then assigned to either a mindful or mindless learning condition. Finally, as a posttest, participants completed the Implicit Association Test and the Inclusion of Nature in the Self Scale. The performance of the mindful-learning group was better for both measures. Participants in the mindful-learning condition performed better on the Implicit Association Test and scored higher on the Inclusion of Nature in the Self Scale. These results provide empirical evidence that mindful learning may promote connectedness to nature, both implicitly and explicitly.

Because they generate excellent images, nanoparticles (NPs), especially biosynthesized NPs, provide a new solution for tumor imaging. In this research, we unveil a novel type of biosynthesized NPs featuring multicolor fluorescence. These NPs exhibit little cytotoxicity to cells. The explored NPs, designated Zn-ZFP-GST NPs (Zinc NPs in abbreviation), are generated from leukemia cells treated with a Zn2+ solution, while zinc-finger protein and glutathione S-transferase (GST) were also identified in the Zinc NPs. Under near-UV illumination, the Zinc NPs simultaneously emit green, yellow, and red fluorescence. In addition, the intensity of the fluorescence increases with the existence of sulfides. Besides, the NPs are encapsulated by microvesicles (MVs) shed from the plasma membrane. As observed in whole-body research of nude mice, the NP-MVs migrate via blood circulation and are distinguished by their fluorescent signals. Furthermore, the folic acid (FA) &AVR2 (human VEGF antibody)-coated NP-MVs are exploited to target the tumor location, and the feasibility of this approach has been confirmed empirically. The Zinc NPs shed light on an alternative solution to tumor detection.

Theory of mind (ToM) encompasses a range of abilities that show different developmental time courses. However, relatively little work has examined the neural correlates of ToM during early childhood. In this study, we investigated the neural correlates of ToM in typically developing children aged 4–8 years using resting-state functional magnetic resonance imaging. We calculated whole-brain functional connectivity with the right temporo-parietal junction (RTPJ), a core region involved in ToM, and examined its relation to children's early, basic, and advanced components of ToM competence assessed by a parent-report measure. Total ToM and both basic and advanced ToM components, but not early, consistently showed a positive correlation with connectivity between RTPJ and posterior cingulate cortex/precuneus; advanced ToM was also correlated with RTPJ to left TPJ connectivity. However, early and advanced ToM components showed negative correlation with the right inferior/superior parietal lobe, suggesting that RTPJ network differentiation is also related to ToM abilities. We confirmed and extended these results using a Bayesian modeling approach demonstrating significant relations between multiple nodes of the mentalizing network and ToM abilities, with no evidence for differences in relations between ToM components. Our data provide new insights into the neural correlates of multiple aspects of ToM in early childhood and may have implications for both typical and atypical development of ToM.

<br>Display Omitted<br>• A new coupled method of stable isotope-labeling derivatization with UA-DLLME was reported. • Simultaneous determination of multiple neurotransmitters with UHPLC-MS/MS. • Heavy labeled d3-MASC standards were used as the internal standards for quantification. • The method was sensitive, accurate and low matrix effect. • Application for neurotransmitters dynamic changes in rats brain microdialysates.<br>In this work, for the first time, a new hyphenated technique of stable isotope-labeling derivatization-ultrasound-assisted dispersive liquid-liquid microextraction has been developed for the simultaneous determination of monoamine neurotransmitters (MANTs) and their biosynthesis precursors and metabolites. The developed method was based on ultra high performance liquid chromatography tandem mass spectrometry detection using multiple-reaction monitoring mode. A pair of mass spectrometry sensitizing reagents, d0-10-methyl-acridone-2-sulfonyl chloride and d3-10-methyl-acridone-2-sulfonyl chloride, as stable isotope probes was utilized to facilely label neurotransmitters, respectively. The heavy labeled MANTs standards were prepared and used as internal standards for quantification to minimize the matrix effects in mass spectrometry analysis. Low toxic bromobenzene (extractant) and acetonitrile (dispersant) were utilized in microextraction procedure. Under the optimized conditions, good linearity was observed with the limits of detection (S/N > 3) and limits of quantification (S/N > 10) in the range of 0.002-0.010 and 0.015-0.040 nmol/L, respectively. Meanwhile, it also brought acceptable precision (4.2-8.8%, peak area RSDs %) and accuracy (recovery, 96.9-104.1%) results. This method was successfully applied to the simultaneous determination of monoamine neurotransmitters and their biosynthesis precursors and metabolites in rat brain microdialysates of Parkinson's disease and normal rats. This provided a new method for the neurotransmitters related studies in the future.

Tibetan medicine "Dida" isoccasionally misused due to its complex origins, which ultimately affects its clinical efficacy. The accurate name, origin, property, and efficacy of "Dida"are highly important for its further research and development. In the present study, by viewing the classic Tibetan medicine and modern literature, and combining the clinical practice of Tibetan medicine, the origins, properties and the clinic effects of "Dida" were defined. "Dida" originated from multiple plant species of Swertia, Gentianopsis, Halenia, Lomatogonium, Comastoma(Gentianaceae), Hedyotis (Saxifragaceae) and Erysimum (Cruciferae). The medicinal properties of "Dida" is mainly bitter and cold. It has been commonly used to treat febrile diseases and hepatic and gall diseases. This study suggested that the relevant herbalogical study, species identification and pharmacological effects of "Dida" should be taken based on the Tibetan medicine theories and clinical practice. Thus the medicine can be better used and ensure its safety and quality simultaneously.

The anterior cingulate cortex (ACC) is part of a network implicated in the development of self-regulation and whose connectivity changes dramatically in development. In previous studies we showed that 3 h of mental training, based on traditional Chinese medicine (integrative body–mind training, IBMT), increases ACC activity and improves self-regulation. However, it is not known whether changes in white matter connectivity can result from small amounts of mental training. We here report that 11 h of IBMT increases fractional anisotropy (FA), an index indicating the integrity and efficiency of white matter in the corona radiata, an important white-matter tract connecting the ACC to other structures. Thus IBMT could provide a means for improving self-regulation and perhaps reducing or preventing various mental disorders.

OBJECTIVE: To investigate the xanthones from Tibetan medicine Halenia elliptica and their antioxidant activity.METHODS: Column chromatography over normal phase silica gel, reversed phase silica gel, Sephadex LH-20, and recrystallization techniques were used to isolate and purify constituents from Halenia elliptica. Infrared spectrometry, mass spectrometry, and nuclear magnetic resonance spectrometry were used to identify the structure of compounds. The antioxidant activity was evaluated by measuring the content of malondialdehyde product in mice liver cell microsomal induced by ferrous-cysteine. RESULTS: Eight xanthones (compound I-VIII) were isolated and identified from the ethyl acetate extract of Halenia elliptica, among which 1,7-dihydroxy-2,3,5-trimethoxyxanthone was a novel compound. Compound I, III at 10 microg/ml and 100 microg/ml could inhibit the production of malondialdehyde in mouse liver microsomes in vitro. CONCLUSION: Eight xanthones were isolated and they have certain antioxidant activity.