Mechanism of Yanghe Pingchaun granules on airway remodeling in asthmatic rats based on IL-6/JAK2/STAT3 signaling axis

Objective: To investigate the effects of Yanghe Pingchuan Granules on airway remodeling in asthmatic rats, and to explore the mechanism of Interleukin-6/Janus kinase 2/ Signal transducing activator of transcription 3(IL-6/JAK2/STAT3) signal axis. Methods: We separated 42 healthy male SD rats into two groups, a control group (7) and a model group (35).The model group was sensitized with a combination of ovalbumin (OVA) and aluminum hydroxide for 2 weeks, while the control group was given an equal amount of physiological saline.After 2 weeks, the modeling group was randomly divided into Model group, Yanghe Pingchuan Granules high, medium and low dose groups and Dexamethasone group, each group consisted of 7 animals. After 4 weeks, OVA atomization and gavage were used for stimulation and treatment. Yanghe Pingchuan Granules high, middle and low groups were given 15.48, 7.74, 3.87 g∙kg-1 Yanghe Pingchuan Granules daily, dexamethasone group was given 0.0625 mg∙kg-1 dexamethasone daily, and the other groups were given the same amount of normal saline. HE, PAS and Masson staining were used to observe the lung histopathological changes in rats. The levels of interleukin-6, IL-23 and IL-17A were detected by ELISA. The expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 in lung tissues were detected by Western blot. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression levels of IL-6, JAK2 and STAT3 in rat lung tissue. Results: The lung tissue structure of the model group was severely damaged compared to the control group, accompanied by a great many of inflammatory cell infiltration, goblet cell hyperplasia, subepithelial collagen fiber deposition and airway epithelial thickening were more obvious. The expressions of IL-6, IL- 23 and IL-17A in serum were significantly increased (P<0.01), the protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and the mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly increased (P<0.01);Compared with the model group, inflammatory cell infiltration, goblet cell proliferation, subepithelial collagen fiber deposition and airway epithelial thickening were significantly reduced in each administration group, and the expressions of IL-6, IL-23 and IL-17A in serum were significantly decreased (P< 0.01). The protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly decreased (P<0.01). Conclusion: Yanghe Pingchuan Granules can significantly alleviate airway remodeling in asthmatic rats, and its mechanism may be through inhibiting the IL-6/JAK2/STAT3 signal axis.

STUDIES ON POLYMERIZATION MECHANISM OF CONJUGATED DIENE WITH η~3-ALLYL RARE EARTH MODEL COMPLEX

(η^-C_H_5)_2CeCl_5Mg_2(tmed)_2 was used as a catalyst to polymerize isoprene,Terminal ends of polyisoprene were identified as -CH_2-CH=CH_,which indicates that the insertion reaction of the monomer occurred between η^-allyl and cerium ion and gives a direct evidence for the η^-allyl mechanism of conjugated diene polymerzation with rare earth coordination catalysts.

Studies on the Reaction Mechanism of CO_2-Reforming of Methane over Co/γ-Al_2O_3 Catalyst

TPPR and XPS characterizations were combined to study the reaction mechanism of CO2reforming of methane to syngas over Co/γ-Al2O3 catalysts. CH4 shows a tendency to form surface carbons by deep dissociation at high temperatures. CO2 dissociation reaction also occurs at >673K. It is believed that carbide carbons are active species to generate CO by rcacting with o atoms dissociated from CO2. In the reaction,Co(0) particles are responsible for dissociating CH4 to form active C. abstracting an O atom from CO2 molecule, and transferring O atom to C to form CO.

THEORETICAL STUDIES ON THE REACTION MECHANISM OF AMMONIA WITH FORMALDEHY DE

The reaction mechanism of ammonia with formaldehyde was investigated by using the intrinsic reaction coordinate(IRC)method on the ab initio RHF/STO-3G basis set. our results indicate that the reaction proceeds in two stages:the first step yields the molecular complex and the second one is the rearrangement from molecular complex to the reaction proauct.

STUDIES ON THE KINETICS AND INITIATION MECHANISM OF ACRYLAMIDE POLYMERIZATION USING CERIC/ACETOACETANILIDE SYSTEM AS INITIATOR

It is found that acetoacetanilide possesses very high promoting reactivity towards ceric ion in initiating polymerization of vinyl monomer. The kinetics of acrylamide polymerization and the activation energies were studied. The initiation mechanism of ceric/acetoacetanilide is proposed on the basis of experimental results of FT-IR and ESR.

STUDIES ON FLUORESCENCE ENHANCING EFFECT AND ALKALINE DEGRADATION MECHANISM OF DOXYCYCLINE AND METHACYCLINE

Degradation reaction of doxycycline or methacycline was carried out in KOH solution and intense fluorescence was obtained.A degradation mechanism of doxycycline or methacycline was suggested.

MHEORETICAL STUDIES ON THE REACTION MECHANISMS OF CYCLOADDITION REACTIONS BETWEEN KETENE OR SUBSTITUTED KETENES AND CYCLOPENTADIENE

The cycloaddition reactions between ketene or substituted ketenes and cyelopentadiene have been studied theoretically by means of the semiempirical AMI method.Three different substituted ketenes have been selected and ten transition states,corresponding to different approach geometries have been located and characterized,The regioselectivity and stereoselectivity of the reactions are correctly predicted by the calculations and the reaction mechanisms are analyzed in terms of electronic and steric effects of the substitutents on the reacting ketene and cyc-lopentadiene.

Mechanism of Wulan Shisanwei Decoction in Treating Hypertension Complicated with Hyperlipidemia Based on Network Pharmacology

[Objectives]To screen out the main effective components of Wulan Shisanwei Decoction in the treatment of hypertension complicated with hyperlipidemia based on the method of network pharmacology,predict the target and explore the possible mechanism.[Methods]13 components of Wulan Shisanwei Decoction were searched on the TCMSP data platform,the corresponding active components were found and the corresponding targets were searched in Pubchem database.GeneCards database was used to screen the corresponding targets of hypertension and hyperlipidemia.The core target PPI network of Wulan Shisanwei Decoction in the treatment of hypertension complicated with hyperlipidemia was constructed by processing in STRING database.The effective data were imported into Cytoscape 3.8.0 to analyze the network topology parameters,and they were screened according to the degree value greater than the average value.Finally,the relevant information about the core target of Wulan Shisanwei Decoction in the treatment of hypertension complicated with hyperlipidemia was obtained.GO enrichment analysis and KEGG pathway analysis were carried out for core targets in DAVID database.The visualization map of"drug-component-target-disease"was drawn by Cytoscape 3.8.0.[Results]A total of 85 active components were obtained from Wulan Shisanwei Decoction,and there were 1532 corresponding targets.A total of 303 key targets were obtained by intersecting corresponding drug targets with disease targets.3178 biological processes were obtained by GO analysis(P<0.05)and 192 signaling pathways were obtained by KEGG enrichment analysis(P<0.05).[Conclusions]It was predicted that the main active components of Wulan Shisanwei Decoction in the treatment of hypertension complicated with hyperlipidemia were stigmasterol,acacetin,pectolinarigenin,isorhamnetin,alizarin,quercetin,nordamnacanthal,kaempferol,luteolin,glyceollin,kushenol,t,3-methylkempferol,ellagic acid,etc.20 core targets were selected in the treatment of hypertension complicated with hyperlipidemia:SRC,STAT3,HSP90AA1,MAPK1,MAPK3,PIK3R1,HRAS,GRB2,PIK3CA,AKT1,PTPN11,ESR1,LCK,EGFR,FYN,EP300,RELA,JUN,LYN,RHOA.These targets were involved in PI3K-Akt signaling pathway,lipid and atherosclerosis,proteoglycan in cancer,Ras signaling pathway,etc.to exert a response to oxidative stress,cellular response to chemical stress,peptidyl-tyrosine phosphorylation and peptide tyrosine modification,and can intervene in the early stage of the disease.It may be the potential mechanism of Wulan Shisanwei Decoction in the treatment of hypertension complicated with hyperlipidemia.

Studies on the Evolutionary Laws and Maintaining Mechanism of Renewability of the Yellow River's Water Resources

The Yellow River has a vast catchment area and historically it is the mother river of the Chinese nation. Now it serves as one of the main theatres for the on-going national campaign to develop China's western hinterland.……

Human Rights NGOs and the United Nations Human Rights Council——Participation by the China Society for Human Rights Studies in the Universal Periodic Review Mechanism

Since its founding in 1993, the China Society for Human Rights Studies （CSHRS） has extensively participated inthe human rights work of the United Nations （UN） and has actively carried out international exchange and cooperation. In May 2012, the UN Human Rights Council （UNHRC） initiated the second round of country reviews on human rights.

Mechanism of the use of four chemotherapeutic drugs for intestinal metaplasia in the treatment of precancerous gastric cancer lesions based on network pharmacology and molecular docking technology

Objective: To use network pharmacology and molecular docking technology to explore material basis and molecular mechanism of Coix lacryma-jobi, Hedyotis diffusa, Curcuma zedoaria, and Salvia chinensis on the treatment of pre-cancerous stomach diseases. Our findings provide a theoretical foundation for further clinical research. Methods: We searched and screened the targets of four pharmaceutical components for activity against precancerous lesions of gastric cancer (PLGC) using the GeneCards and OMIM network databases. The Chinese medicine composition-target network was constructed using Cytoscape3.7.2 software, and the protein interoperability network of the four drugs for PLGC treatment was constructed using the string data platform. The core target was found by topological analysis. Finally, biopathic and enrichment analyses were carried out on the drug-disease intersection target. Results: A total of 19 active ingredients and 123 component targets were collected for four enterolytic drugs. For PLGC, 1487 targets were identified, and 64 targets were collected for pharmaceutical components and diseases. A topological analysis was performed with a value greater than the mean degree (29.0), and 64 key core targets were obtained (including TP53, EGFR, TNF, and VEGFA), and the key targets were screened for TP53, EGFR, TNF, and VEGFA, among others, through network topology and protein interoperability network analyses. GO functional enrichment analysis resulted in 1337 bio-process entries, 46 cell composition entries, and 74 molecular function entries. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis and screening resulted in 254 signaling pathways, including stomach cancer, breast cancer, prostate cancer, non-small cell lung cancer, and colon cancer. Conclusion: The four enterolysis drugs may be used to prevent and control PLGC by acting on TP53, EGFR, TNF, and VEGFA targets and relevant gastric cancer, inflammatory, and immune pathways.

Mechanism study on UV-induced photodegradation of nonylphenol ethoxylates by intermediate products analysis

Photodegradation of nonylphenol ethoxylates （NPloEO） was investigated in laboratory scale under UV irradiation. The intermediate photodegradation products were analyzed by LC-ESI-MS. Three kinds of intermediate products including aldehydic compounds, carboxylic compounds and cyclohexanyl compounds were identified. Five main degradation routes involving the oxidation of the alkyl chain and ethoxylate unit, shortening of the alkyl chain and ethoxylate unit, hydrogenation of the benzene ring were proposed.

Chemiluminescence determination of 20 amino acids and the mechanism study

It was found that 20 amino acids could inhibit the intensity of the luminol-H_2O_2-CuSO_4 chemiluminescence system.Using this character,a rapid and sensitive method for the determination of 20 amino acids was developed with flow injection coupled with chemiluminescence detection.Under the optimal conditions,the detection limits of 20 amino acids were in the range of 4.5×10^（-7）- 4.3×10^（-10） mol/L,and the relative standard deviations were less than 3.2%.The proposed method was successfully applied to drug analysis.The possible mechanism was also discussed.

Okadaic acid: a tool to study regulatory mechanisms for neurodegeneration and regeneration in Alzheimer's disease

Okadaic acid： Okadaic acid （OKA）, a polyether （C38 fatty acid） toxin, is a potent and selective inhibitor of protein phosphatase, PP1 and protein phosphatase 2A （PP2A）. It is mainly extracted from a black sponge Hallichondria okadaii and has been suggested to play a potent probe for studying the various molecular, cellular, biochemical and mechanism of neurotoxicity. It is known as a selective and potent in- hibitor of serine/threonine phosphatases 1 and 2A induces hyperphosphorylation of tau in vitro and in vivo. It has been reported that Alzheimer＇s disease （AD） is a complex multi- factorial neurodegenerative disorder and hyperphosphor- ylated tau protein is a major pathological hallmark of AD. The reduced activity of phosphatases like, PP2A has been implicated in the brain of AD patients. OKA also induced inhibition of protein phosphatases cause neurofibrillary tangles （NFTs） like pathological changes and tau hyperphos- phorylation seen in AD pathology. Our and others reports inferred that OKA induces neurodegeneration along with tau hyperphosphorylation, GSK3β activation, oxidative stress, neuroinflammation and neurotoxicity which are char- acteristic of AD pathology （Figure 1）.

A Numerical Study on the Mechanisms Producing Forces on Cylinders Interacting with Stratified Shear Environments

A three dimensional(3D)numerical wave flume is used to investigate carefully the ISWs(Internal solitary wave)forces acting on cylinders interacting with a stratified shear environment.Using the Large-Eddy Simulation(LES)approach and analyzing the distribution of shear stress and pressure along the surface of the cylinder,the differential pressure resistance and the viscous force are obtained.The method of multiple linear regression analysis is adopted and a comprehensive influence coefficient is determined accordingly to account for the dimensionless forces acting on the cylinder.Results show that the differential pressure resistance on a square cylinder is 1.5 times higher than that on a circular cylinder in the upper layer,while the differential pressure resistance on a square cylinder is 3.5 times larger than that on a circular cylinder in the lower layer.The viscous force is 1–2 orders of magnitude smaller than the differential pressure resistance,which means that the viscous force could be ignored.The comprehensive influence coefficient shows positive correlation with the relative wave height and negative correlation with upper and lower water depth ratio.

Uneven aftershock distribution of Wenchuan Ms8.0 earthquake and possible mechanism

The aftershock activity of Wenchuan Ms8.0 earthquake showed different spatial and temporal distri- butions along two different segments of the Longmenshan fault. This difference was likely the result of segmentation of the earthquake rupture process, which in turn may be the result of the fault＇ s segmentation in its long-term geotectonic condition.

Clinical Observation on Treatment of 78 Patients of B-Thalassemla with Bushen Ylsul (补肾益髓) Method and Study on Its Molecular Mechanism

Objective: To study the treatment of B-Thalas-semia (ThE) with Chinese herbal medicine for Bushen Yisui (BSYS), its theoretical base and molecular mechanism. Methods: Seventy-eight patients with ThE were treated with BSYS recipe (consisted of 11 Chinese herbal drugs as Dogwood fruit, Fleeceflower root, prepared Rehmannia root and turtle shell, etc.) orally taken, 3 times per day, 10 g/time, 3 months as one therapeutic course. Hemoglobin (Hb), red blood cell (RBC), reticulocyte (Ret) and hemoglobin F (HbF) were checked every month. At the same time, PAGE, PVR, PCR-SSCP, RT-PCR, DNA series analysis, mRNA gene expression analysis techniques were used to conduct the systematic gene analysis in patients to study the molecular mechanism of TCM treatment from aspects of gene mutation, gene expression and control-regulation. Results: All the blood criteria in patients after BSYS treatment were improved significantly with clinical symptoms

Parametric study of control mechanism of cortical bone remodeling under mechanical stimulus

The control mechanism of mechanical bone remodeling at cellular level was investigated by means of an extensive parametric study on a theoretical model described in this paper. From a perspective of control mechanism, it was found that there are several control mechanisms working simultaneously in bone remodeling which is a complex process. Typically, an extensive parametric study was carried out for investigating model parameter space related to cell differentiation and apoptosis which can describe the fundamental cell lineage behaviors. After analyzing all the combinations of 728 permutations in six model parameters, we have identified a small number of parameter combinations that can lead to physiologically realistic responses which are similar to theoretically idealized physiological responses. The results presented in the work enhanced our understanding on mechanical bone remodeling and the identified control mechanisms can help researchers to develop combined pharmacological-mechanical therapies to treat bone loss diseases such as osteoporosis.

DFT Investigation on the Mechanism of Pd(0) Catalyzed Sonogashira Coupling Reaction

Based on DFT calculations, the catalytic mechanism of palladium（0） atom, commonly considered as the catalytic center for Sonogashira cross-coupling reactions, has been analyzed in this study. In the cross-coupling reaction of iodobenzene with phenylacetylene without co-catalysts and bases involved, mechanistically plausible catalytic cycles have been computationally identified. These catalytic cycles typically occur in three stages： 1） oxidative addition of an iodobenzene to the Pd（0） atom, 2） reaction of the product of oxidative addition with phenylacetylene to generate an intermediate with the Csp bound to palladium, and 3） reductive elimination to couple the phenyl group with the phenylethynyl group and to regenerate the Pd（0） atom. The calculations show that the first stage gives rise to a two-coordinate palladium （Ⅱ） intermediate （ArPdI）. Starting from this intermediate, the second oxidative stage, in which the C–H bond of acetylene adds to Pd（Ⅱ） without co-catalyst involved, is called alkynylation instead of transmetalation and proceeds in two steps. Stage 3 of reductive elimination of diphenylacetylene is energetically favorable. The results demonstrate that stage 2 requires the highest activation energy in the whole catalysis cycle and is the most difficult to happen, where co-catalysts help to carry out Sonogashira coupling reaction smoothly.