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Metabolomics responses of Bambusa pervariabilis ¡Á Dendrocalamopsis grandis varieties to Biotic (pathogenic fungus) stress

Bambusa pervariabilis ¡Á Dendrocalamopsis grandis blight, caused by Arthrinium phaeospermum, is one of the most common and serious diseases in bamboo and occurs in the newly born twigs. Bamboo has suffered large dead areas, including more than 3000 hm2, which greatly threatens the process of returning farmlands to forests and the construction of ecological barriers. To identify differential metabolites and metabolic pathways associated with B. pervariabilis ¡Á D. grandis to A. phaeospermum, ultra-performance liquid chromatography (UPLC) and quadrupole-time of flight (Q-TOF) Mass Spectrometry (MS) combined with a data-dependent acquisition method was used to analyse the entire sample spectrum. In total, 13223 positive ion peaks and 10616 negative ion peaks were extracted. OPLS-DA and several other analyses were performed using the original data. The OPLS-DA models showed good quality and had strong predictive power, indicating clear trends in the analyses of the treatment and control groups. Clustering and KEGG pathway analyses were used to screen the differential metabolites in the treatment and control groups from the three B. pervariabilis ¡Á D. grandis varieties and reflected their metabolic responses induced by A. phaeospermum infection. The results showed that the three B. pervariabilis ¡Á D. grandis varieties mode showed significant changes in the following six resistance-related metabolites after A. phaeospermum invasion in positive and negative ion modes: proline, glutamine, dictamnine, apigenin 7-O-neohesperidoside, glutamate, and cis-Aconitate. The following four main metabolic pathways are involved: Arginine and proline metabolism, Glyoxylate and dicarboxylate metabolism, Biosynthesis of alkaloids derived from shikimate pathway, and Flavone and flavonol biosynthesis. This study lays a foundation for the later detection of differential metabolites and metabolic pathways for targeting, and provides a theoretical basis for disease-resistant breeding and the control of B. pervariabilis ¡Á D. grandis blight.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H68N | ChemSpider

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Enzymes are biological catalysts that produce large increases in reaction rates and tend to be specific for certain reactants and products. I hope my blog about is helpful to your research. Synthetic Route of 827-61-2

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IDrugs and idevices discovery research: Preclinical assays, techniques, and animal model studies for ocular hypotensives and neuroprotectants

Discovery ophthalmic research is centered around delineating the molecular and cellular basis of ocular diseases and finding and exploiting molecular and genetic pathways associated with them. From such studies it is possible to determine suitable intervention points to address the disease process and hopefully to discover therapeutics to treat them. An investigational new drug (IND) filing for a new small-molecule drug, peptide, antibody, genetic treatment, or a device with global health authorities requires a number of preclinical studies to provide necessary safety and efficacy data. Specific regulatory elements needed for such IND-enabling studies are beyond the scope of this article. However, to enhance the overall data packages for such entities and permit high-quality foundation-building publications for medical affairs, additional research and development studies are always desirable. This review aims to provide examples of some target localization/verification, ocular drug discovery processes, and mechanistic and portfolio-enhancing exploratory investigations for candidate drugs and devices for the treatment of ocular hypertension and glaucomatous optic neuropathy (neurodegeneration of retinal ganglion cells and their axons). Examples of compound screening assays, use of various technologies and techniques, deployment of animal models, and data obtained from such studies are also presented.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H82N | ChemSpider

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Correlation between pKa and reactivity of quinuclidine-based catalysts in the Baylis-Hillman reaction: Discovery of quinuclidine as optimum catalyst leading to substantial enhancement of scope

The reactivity of a variety of quinuclidine-based catalysts in the Baylis-Hillman reaction has been examined, and a straightforward correlation between the basicity of the base and reactivity has been established, without exception. The following order of reactivity was established with pKa’s of the conjugate acids (measured in water) given in parentheses: quinuclidine (11.3), 3-hydroxyquinuclidine (9.9), DABCO (8.7), 3-acetoxyquinuclidine (9.3), 3-chloroquinuclidine (8.9), and quinuclidinone (7.2). The higher than expected reactivity of DABCO, based on its pKa, was analyzed by comparing the relative basicity of DABCO and 3-acetoxyquinuclidine in DMSO. It was found that in aprotic solvent, DABCO was 0.6 pKa units more basic than 3-acetoxyquinuclidine, thus establishing a direct link between pKa of the amine and its reactivity. In contrast to previous literature work that reported the contrary, quinuclidine, which has the highest pKa, was found to be the most active catalyst. The reaction profile with quinuclidine showed significant autocatalysis, which suggested that the presence of proton donors might further enhance rates. Thus, a series of additives bearing polar X-H bonds were investigated and it was found that methanol, triethanolamine, formamide, and water all provided additional acceleration. Methanol was found to be optimum, and the powerful combination of quinuclidine with methanol was tested with a host of aldehydes and Michael acceptors. Not only were the reactions more efficient and faster than previously reported, but now new substrates that were previously unreactive could be employed. Notable examples include the use of acetylenic aldehydes and the employment of vinyl sulfones, acrylamides, delta-lactones, and even alpha,beta-unsaturated esters bearing a beta-substituent.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H45N | ChemSpider

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COMPOSITIONS AND METHODS FOR THE TREATMENT OF PRESBYOPIA

The invention provides compositions and methods for the treatment of presbyopia. The compositions preferably use aceclidine separate or together with a cycloplegic agent and/or with a nonionic surfactant and viscosity enhancer, and or with low concentrations of a selective a-2 adrenergic receptor agonist.

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The interaction of the enantiomers of aceclidine with subtypes of the muscarinic receptor

The pharmacological activity of the enantiomers of aceclidine was investigated in Chinese hamster ovary cells transfected with the M1 through M5 subtypes of the muscarinic receptor and also in the rat heart and parotid gland that express primarily M2 and M3 receptors, respectively. When measured by stimulation of phosphoinositide hydrolysis in Chinese hamster ovary cells transfected with the M1, M3 and M5 muscarinic subtypes, the potency of S-(+)-aceclidine was approximately 2- to 4-fold greater than that of R-(-)-aceclidine, whereas the maximal response of the R-(-)-isomer was only 44 to 64% that of the S-(+)-isomer. When measured by inhibition of forskolin-stimulated cyclic AMP accumulation in Chinese hamster ovary cells transfected with the M2 and M4 muscarinic subtypes, the potency of S-(+)- aceclidine was approximately 3.5-fold greater than that of R-(-)-aceclidine. In cells transfected with the M2 muscarinic receptor, the maximal responses of the enantiomers were the same, whereas the maximal response of R-(-)- aceclidine was 86% that of S-(+)-aceclidine in cells transfected with the M4 muscarinic subtype. The activities of the enantiomers of aceclidine at native M2 and M3 muscarinic receptors coupled to inhibition of adenylyl cyclase activity in the heart and stimulation of phosphoinositide hydrolysis in the parotid gland, respectively, were similar to those observed in Chinese hamster ovary cells transfected with the corresponding receptor subtypes. We devised a simple quantitative method for using our data in Chinese hamster ovary cells to predict the relative potencies of agonists in a more sensitive assay in which the agonists produce a full maximum response. By using this method, we were able to predict the relative potencies of the enantiomers for eliciting contractions in the guinea pig ileum, an M3 muscarinic response, from their activity in Chinese hamster ovary cells transfected with the M3 muscarinic subtype. Our method of analysis should have application in a variety of studies in which transfected cells are used to determine the pharmacological activity of agonists.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H55N | ChemSpider

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Design, synthesis, and neurochemical evaluation of 5-(3-alkyl-1,2,4- oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidines as M1 muscarinic receptor agonists

A series of 5-(3-alkyl-1,2,4-oxadiazol-5-yl)-1,4,5,6- tetrahydropyrimidines (7a-h) was synthesized for biological evaluation as selective agonists for M1 receptors coupled to phosphoinositide (PI) metabolism in the central nervous system. Each ligand bound with high affinity to muscarinic receptors from rat brain as measured by inhibition of [3H]-(R)-quinuclidinyl benzilate ([3H]-(R)-QNB) binding. 5-(3-Methyl- 1,2,4-oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidine trifluoroacetate (CDD- 0098-J; 7a) displayed high affinity (IC50 = 2.7 ¡À 0.69 muM) and efficacy at muscarinic receptors coupled to PI metabolism in the rat cortex and hippocampus. Increasing the length of the alkyl substituent increased affinity for muscarinic receptors yet decreased activity in PI turnover assays. The hippocampal PI response of 7a was blocked by lower concentrations of pirenzepine (8) or by higher concentrations of either AF-DX 116 (9) or p- fluorohexahydrosiladifenidol (10), suggesting that at low concentrations 7a selectively stimulates PI turnover through M1 receptors.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H54N | ChemSpider

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Process for preparing salt of hyaluronic acid with a pharmaceutically active substance

Pharmaceutical preparations for topical administration containing a pharmacologically active substance together with hyaluronic acid or a molecular weight fraction thereof. The hyaluronic acid may be in the form of the free acid or may be a salt with an alkali or alkaline earth metal, magnesium, aluminum or ammonium, or in the form of a salt with one or more pharmacologically active substances.

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Quinuclidine – Wikipedia,
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Pharmacological strategies for presbyopia correction

Purpose: To summarize the pharmacological strategies that are being explored for presbyopia correction. Methods: The review concentrates on pharmacologically induced pupillary miosis to increase depth-of-focus and lens softening or other measures to restore active accommodation. Results: Several studies suggest that near vision improves and distance vision is unaffected for many hours after either monocular or binocular instillation of any one of several drug combinations that cause miosis. Unfortunately, in most studies, measurements were limited to photopic visual acuity for near and distance vision, whereas it is anticipated that pupil constriction may have adverse effects on mesopic and scotopic vision. It is not clear whether improved near vision was due entirely to increased depth-of-focus, or whether, for example, a drug-induced myopic shift in refraction was also involved. Currently, no study has provided direct evidence for drug-induced restoration/enhancement of true accommodation involving an ocular power change. Conclusions: Although it is possible that, in the future, pharmacological drops may offer a safe and reliable solution for presbyopia correction, more evidence of their effectiveness and limitations is required.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H74N | ChemSpider

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Visible-Light-Mediated Metal-Free Difunctionalization of Alkenes with CO2 and Silanes or C(sp3)?H Alkanes

Catalytic alkene difunctionalization via Si?H and C?H activations represents an ideal atom- and step-economic pathway for quick assembly of molecular complexity. We herein developed a visible-light-promoted metal-free difunctionalization of alkenes using abundant CO2 and readily available Si?H and C(sp3)?H bonds as feedstocks. Through the merger of photoredox and hydrogen-atom-transfer catalysis, a variety of value-added compounds, such as beta-silacarboxylic acids and acids bearing a gamma-heteroatom (e.g., N, O, S) could be directly accessed from simple alkenes in a redox-neutral fashion.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H63N | ChemSpider

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Drugs, leads, and drug-likeness: an analysis of some recently launched drugs.

An analysis of the origins of recently launched drugs reveals that most were derived by modification of known drug structures or from lead structures obtained from the scientific literature. High-throughput screening did not have a significant impact on the derivation of these drugs. The drug structures are very closely related to their leads.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H79N | ChemSpider