53 results about "Syringic acid" patented technology

A composition, usable for removing a biofilm and necrotic or infected tissues from skin lesions and lesions of the oral cavity, comprises methanesulfonic acid 99.0% and a proton acceptor. The proton acceptor is selected from the group consisting of: anhydrous sodium carbonate, 5-amino-2-mercaptobenzimidazole, ethylenediaminetetraacetic acid tetrasodium salt, sodium gluconate, sodium tartrate dihydrate, 2-mercapto-5-benzimidazole sodium sulfonate, dimethyl sulfoxide, polyethylene glycol 400, polyethylene glycol 600, silicon dioxide, tetraethoxysilane, and mixtures thereof. The aforesaid composition can be prepared in the form of a solution, gel or cream.

The invention provides an acrylamide generation inhibitor and a method for inhibiting acrylamide generation. The acrylamide inhibitor is syringic acid, vanillic acid or sinapic acid. The syringic acid and the vanillic acid can passivate polyphenol oxidase in the food processing process and prevent polyphenol oxidase from oxidizing polyphenol in food into quinone, and the sinapic acid can directly inhibit quinone generated by oxidizing polyphenol, so that the content of Maillard reaction substrates is reduced, and the yield of the Maillard reaction products is improved. The structure of quinone is extremely similar to that of an intermediate product dicarbonyl compound in a path for producing acrylamide through Maillard reaction, so that quinone and asparagine can be subjected to Maillard reaction under a high-temperature condition to generate acrylamide. Therefore, the Maillard reaction is prevented by passivating the activity of polyphenol oxidase or inhibiting the generation of quinone oxidized by polyphenol, the generation of 2A cancerogen acrylamide easily generated in the high-temperature food processing process is further inhibited, the purpose of healthy diet is achieved, and a new thought is provided for controlling the generation of acrylamide in the food processing process.

The invention belongs to the technical field of high polymer materials and coatings, and relates to waterborne polyurethane, an emulsion containing the waterborne polyurethane as well as a preparation method and application of the emulsion. The preparation method of the emulsion containing the waterborne polyurethane comprises the following steps: dehydrating the polytetrahydrofuran ether glycol in vacuum; then adding isophorone diisocyanate, dibutyltin dilaurate and butanone, and carrying out a heat preservation reaction to obtain a prepolymer; then adding 1, 4-butanediol, 3-dimethylamino-1, 2-propylene glycol, a defoaming agent, a dispersing agent and a flatting agent, and carrying out further heat preservation reaction; adding syringic acid and acetic acid for reaction; adding water to emulsify to obtain a waterborne polyurethane emulsion; according to the application, the emulsion is used for preparing the polyurethane moisture-permeable microporous membrane. The prepared polyurethane moisture-permeable microporous membrane has good water resistance, moisture permeability, antibacterial and antifouling properties and strength, and can meet the application requirements of multiple fields.

The invention discloses Chinese angelica traditional Chinese medicine decoction pieces and a processing method thereof, and belongs to the technical field of traditional Chinese medicine processing. According to the invention, a bio-based eutectic solvent system is adopted, L-proline and syringic acid form a stable complexing structure through pi-pi accumulation and hydrogen-bond interaction, and the dissolution rate of active ingredients is improved by cooperating with the conjugation effect of hydrophobic groups and benzene rings of gamma-nonanolactone; nano cellulose crystals pretreated by sulfuric acid are introduced, surface hydroxyl groups of the nano cellulose crystals and DES components form a hydrogen bond network, a three-dimensional thermal stable structure is constructed, active components are effectively wrapped, and high-temperature degradation is prevented; the low surface tension of the gamma-nonanolactone is utilized to quickly permeate into the cell walls of the medicinal materials, and the magnetic eddy shear force is combined to destroy the fiber structure and accelerate the component release; trehalose is adopted as a freeze-drying protective agent, oil phase agglomeration is inhibited by forming an amorphous glassy state, and the structural integrity of thermosensitive components is protected by hydroxyl hydrogen bonds. No organic solvent is left, medicine residues are subjected to DES secondary extraction and then cooperatively processed with fresh angelica sinensis, and efficient recycling of resources is achieved.

The invention belongs to the field of biological pharmacy, and particularly relates to a phenolic acid composition and application thereof in promoting digestion. According to the invention, monophenolic acid for improving dyspepsia is found through a single-component phenolic acid experiment, and then a phenolic acid compound with a synergistic effect is searched in a compounding manner, so that unexpectedly, the combination of two phenolic acids with the best digestion promoting effect cannot realize the effect optimization; on the contrary, syringic acid with the worst digestion promoting effect is compounded with other phenolic acids, so that the synergistic digestion promoting effect is achieved, the effect of a positive medicine can be achieved, and a potential optional medicine is provided for improving dyspepsia.

The invention discloses a hydrazide compound taking syringic acid as a lead as well as a preparation method and application of the hydrazide compound, and a biological activity test result shows that all the compounds have excellent and broad-spectrum antibacterial activity on tested plant pathogenic fungi. Wherein the inhibition effect of most target compounds on plant pathogenic fungi is superior to that of positive control boscalid, the compound 11 has the best antibacterial effect on rhizoctonia solani, fusarium graminearum, alternaria solani, colletotrichum frutescens and colletotrichum sorghum, and EC50 values of the compound 11 are respectively 0.258 [mu] g / mL, 0.679 [mu] g / mL, 0.424 [mu] g / mL, 0.384 [mu] g / mL and 0.975 [mu] g / mL; for colletotrichum gloeosporioides, the compound 12 has the best antibacterial effect, and the EC50 value of the compound 12 is 0.989 mu g / mL; and secondly, a compound 11 with an EC50 value of 1.248 [mu] g / mL. The hydrazide compound prepared by taking syringic acid as a lead has excellent, broad-spectrum and efficient plant pathogenic microorganism resisting activity, and can be used for preventing and treating plant diseases caused by plant pathogenic microorganisms.

The present invention belongs to the technical field of biological medicine, and discloses a ceramide compound shown in Chemical Formula I: #imgabs0# wherein, R 1 is selected from the residues after condensation of sialic acid, chelidamic acid monohydrate, 2,5-furandicarboxylic acid, quinic acid, chlorogenic acid, ectoine, nicotinic acid, shikimic acid, glucuronic acid, salicylic acid, carnosic acid, dihydrooat acylanthranilic acid, abietic acid, ursolic acid, tranexamic acid, syringic acid, gentisic acid, vanillic acid, 5-hydroxyisovanillic acid, orotic acid, 5-aminoorotic acid, 3,5-dihydroxy-4-methylbenzoic acid, glycyrrhizic acid or gallic acid, R 2 is selected from one of the following structures: -C 15 H 29 、-C 15 H 31 、-C 15 H 27 、-CHOHC 14 H 27 、-CHOHC 14 H 29 . The present invention also discloses a preparation method and application of the ceramide compound. The present invention introduces a molecular fragment with physiological activity of a functional carboxylic acid into ceramide, which will enhance the original efficacy of this type of molecule and also improve the physicochemical properties of the ceramide compound.

The present application belongs to the field of biopharmacy, and particularly relates to a phenolic acid composition and application thereof in promoting digestion. The present application firstly finds a single phenolic acid for improving dyspepsia through single-component phenolic acid experiments, then attempts to find a phenolic acid compound with a synergistic effect through compounding, and surprisingly, the combination of two phenolic acids with the best effect on promoting digestion cannot achieve the best effect optimization, but eugenol with the worst effect on promoting digestion achieves a synergistic effect on promoting digestion through compounding with other phenolic acids, and can achieve the effect of a positive drug, which provides a potential alternative drug for improving dyspepsia.

The present application relates to a kind of Huahong composition effective part extract and its preparation method, the Huahong composition effective part extract includes the following components: syringic acid, new chlorogenic acid, deacetyl carlina acid methyl ester, geniposidic acid, N-acetyl-L-tyrosine, fraxidin, 4-pyridoxinic acid, 7,8-dihydroxy-4-methyl coumarin, chlorogenic acid, ferulic acid;The total content of above components is 80%-95% of effective part extract.The Huahong composition effective part extract of the present application is from the effective part of Huahong composition.

A process for lignin depolymerization is disclosed herein. The process comprises providing a solution comprising dissolved lignin; adding an oxidation catalyst to the solution comprising dissolved lignin; and heating the solution to provide a depolymerized lignin product. Also disclosed is a depolymerized lignin product comprising at least one or more of the following: vanillin at 15-25 wt. %; apocynin at 6-12 wt. %; acetosyringone at 12-15%; syringaldehyde at 13-30 wt. %; syringic acid at 16-24 wt. %; vanillic acid at 5-15 wt. % for use as a cosmetic ingredient and / or food additive.

The invention discloses a method for determining eight active components in dendrobium or cosmetics, which comprises the following steps: (1) pretreating a sample to obtain a solution for instrumental analysis; (2) detecting the eight active components in the sample by adopting a liquid chromatography-mass spectrometry method; the eight active ingredients are quercetin, naringenin, rutin, apigenin, caffeic acid, ferulic acid, syringic acid and chlorogenic acid. According to the method disclosed by the invention, extraction, chromatographic separation and mass spectrum quantification and qualitation of eight active substances including quercetin, naringenin, rutin, apigenin, caffeic acid, ferulic acid, syringic acid and chlorogenic acid in the dendrobe and the cosmetics are realized, and a technical support and a scientific basis are provided for research on efficacy relevance of active components of the dendrobe in the cosmetics.

The application discloses a kind of hydrazine compounds with eugenol as lead and its preparation method and application, and the biological activity test result shows that all compounds are excellent, broad-spectrum antibacterial activity to the plant pathogenic fungi tested.The inhibition effect of most target compounds on plant pathogenic fungi is better than that of positive control rynaxapyr, and the antibacterial effect of compound 11 on rhizoctonia solani, fusarium graminearum, alternaria solani, phoma exigua var. horii and phoma sorghicola is the best, and the EC 50 Values are 0.258 μg / mL, 0.679 μg / mL, 0.424 μg / mL, 0.384 μg / mL and 0.975 μg / mL respectively; for the gossypium gossypium, the antibacterial effect of compound 12 is the best, and the EC 50 Value is 0.989 μg / mL; followed by compound 11, and the EC 50 Value is 1.248 μg / mL.The hydrazine compounds prepared with eugenol as lead have excellent, broad-spectrum and high-efficiency anti-plant pathogenic microorganism activity, and can be used for preventing and treating plant diseases caused by plant pathogenic microorganisms.

The invention discloses an upatinib eutectic crystal form as well as a preparation method and application thereof, and belongs to the technical field of medicinal chemistry. The invention provides an eutectic crystal form I formed by upatinib and vanillic acid and an eutectic crystal form G formed by upatinib and syringic acid, which have definite and reproducible characteristic X-ray powder diffraction pattern and melting point, have excellent solubility in an aqueous medium, do not generate crystal form transformation after being stored for 1 month under the condition of relative humidity of 40 DEG C / 75%, and can be used for preparing a crystal form of upatinib. And the stability is good. The preparation process route is short, the operation condition is mild, the used solvent is conventional, the target eutectic can be efficiently and repeatedly obtained, the defects that some existing eutectic preparation processes are complex, long in period or harsh in condition are overcome, and the method has good process amplification and industrialization prospects.

The application discloses a night work activating composition containing multiple plant extract, which comprises the following components in mass: 3-5 parts of extract A, 10-15 parts of extract B, 2-4 parts of extract C, 1.5-3 parts of curcumin nano-liposome, 2-5 parts of lactobacillus fermentation filtrate, 1-3 parts of lock water magnetite, 0.1-0.3 parts of xanthan gum / acrylate compound thickening agent and 0.5-1 part of preservative composition. The night work activating composition containing multiple plant extract of the application is compounded by extract A with methyl jasmonate as a target component, extract B with rhodioside and syringic acid as target components and curcumin nano-liposome, compared with the same kind of products on the market, the antioxidant and anti-glycation capacity of the night work activating composition can be targetedly strengthened, the transdermal efficiency is improved, and the DNA repair effect and anti-inflammatory effect are improved.

The invention relates to a method for the selective electro-oxidative fragmentation of lignin using an electrochemical system, comprising the following steps: (i) synthesis of a nickel-cobalt electrocatalyst; (ii) obtaining an anode coated with the electrocatalyst; and (iii) selective fragmentation and oxidation of solubilised lignin in an electrochemical reactor comprising said anode, in which vanillic acid and syringic acid are obtained as preferred products.

The present invention provides a phenolic acid modified chitosan, a phenolic acid modified chitosan hydrogel and an application thereof, and specifically relates to the technical field of medical materials. The preparation method of the phenolic acid modified chitosan is to add an amino activator to a chitosan solution and mix in the dark, then add a phenolic acid solution and mix evenly, and finally drop a carboxyl activator to react in the dark to obtain the phenolic acid modified chitosan; wherein the phenolic acid includes syringic acid, gentisic acid, vanillic acid or protocatechuic acid. The amino activation process is carried out under light-proof conditions, which helps to improve the selectivity of the reaction, so that the amino activator and chitosan can react more effectively instead of causing unnecessary side reactions; at the same time, the grafting reaction is carried out in the dark, which can also improve the grafting rate, that is, the proportion of phenolic acid successfully grafted onto chitosan. The preparation method is beneficial to protecting reactants and intermediates, improving the selectivity of the reaction and the quality of the final product, and the process is continuous, which is conducive to industrial large-scale production.

The invention provides a honey variety identification method based on amino acid and polyphenol compounds and application of the honey variety identification method, and relates to the technical field of honey variety detection. According to the invention, amino acids and polyphenol compounds in 14 honey varieties are analyzed by adopting a PLS-DA analysis method, and characteristic difference indexes with VIP values greater than 1 are screened out, specifically trans-cinnamic acid, protocatechuic acid, Pro, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 13, 13, 13, 13, 13, 13, 13, 13, 13, 13, 13, 13, 14 According to the method, 2, 4-dimethylcinnamic acid, rosmarinic acid, apigenin, Tyr, vanillic acid, cumaric acid, isoferulic acid, Cys, caffeic acid phenethyl ester, Met, Asp, gallic acid, naringenin, p-cumaric acid, ferulic acid, rhinoceroic acid, chrysin and syringic acid are screened, and then screened characteristic difference index data is used for establishing a linear discrimination model and a random forest prediction model. Through verification, the linear discrimination model and the random forest prediction model constructed by the method can be accurately and efficiently used for discriminating honey varieties.

The invention relates to the technical field of textiles, in particular to an anti-aging wear-resistant tarpaulin and a preparation method thereof, the anti-aging wear-resistant tarpaulin comprises the following components: 1-3 parts by weight of a composite antioxidant, 75-85 parts by weight of polyester fiber, 9-13 parts by weight of 2-hydroxy-4-methoxybenzophenone, 0.8-1.4 parts by weight of nano silicon dioxide and 0.1-0.5 part by weight of polyvinyl butyral; wherein the composite antioxidant is formed by surface modification of syringic acid and 2-(trifluoromethyl) sulfonamide ethanol according to a mass ratio of 1: (0.5-2); by using the antioxidant compounded by syringic acid and 2-(trifluoromethyl) sulfonamide ethanol, the tarpaulin can more effectively scavenge free radicals so as to delay the aging process of the material, and by using the structural characteristics of the 2-(trifluoromethyl) sulfonamide ethanol, the intermolecular force and hydrophobic property inside the material are improved, so that the tarpaulin can be used as a novel tarpaulin, and the service life of the tarpaulin is prolonged. Therefore, the overall strength, wear resistance and waterproofness of the material are enhanced.

The application discloses a preparation method of a eugenol-based aromatic dibasic acid and application thereof. The preparation method comprises the following steps: heating and refluxing reaction of chloroacetic acid and eugenol in an alkaline solution, acidification to obtain a crude product after the reaction is completed, and obtaining the eugenol-based aromatic dibasic acid after post-treatment of the crude product. The eugenol-based aromatic dibasic acid synthesized by using the widely-sourced eugenol as a raw material is green and environment-friendly, can be used for synthesizing a bio-based polyamide, and has excellent mechanical properties and good dissolving and processing capacity, and the bio-based polyamide has high economy. The whole preparation process is simple in operation and easy to popularize.

The invention belongs to the technical field of medicines, and particularly relates to application of hibiscus (the hibiscus is a plant hibiscus flower and an extract and an active monomer thereof) in preparation of medicines for treating stomach diseases (atrophic gastritis, gastric mucosal lesion and gastric cancer). The invention discloses application of hibiscus syriacus in treatment of gastric diseases. The application comprises at least one of chronic atrophic gastritis treatment, gastric mucosa protection and gastric cancer prevention. In-vitro experiments show that the shrub althea flower extract, shrub althea flower polyphenol, syringic acid (I), protocatechuic acid (II), kaempferol (III) and kaempferol-7-O-beta-D-glucoside (IV) have obvious antioxidant activity and gastric mucosa protection activity, can obviously reduce the ROS content in ethanol-induced GES-1 cells and the expression of apoptosis marker protein Caspase-3 / Bax, and have a wide application prospect.

The application provides a construction method of UPLC characteristic spectrum of Qinglongyi medicinal material, standard decoction and formula granules, comprising the following steps: dissolving and extracting raw materials of the test sample by using a solvent to obtain a test solution; determining the test solution by using high performance liquid chromatography to obtain the UPLC characteristic spectrum of Qinglongyi medicinal material, standard decoction and formula granules; and the high performance liquid chromatography conditions are as follows: a C 18 column is used as the chromatographic column; acetonitrile solution is used as mobile phase A, and 0.1% formic acid aqueous solution is used as mobile phase B, and gradient elution is adopted. The application adopts the high performance liquid chromatography, selects acetonitrile-0.1% formic acid solution as the mobile phase for gradient elution, takes protocatechuic acid, vanillic acid, syringic acid, ellagic acid, rutin and quercitrin as the reference substances, establishes the UPLC characteristic spectrum method of Qinglongyi medicinal material, standard decoction and formula granules, and provides more scientific technical means for controlling the medicinal quality of Qinglongyi medicinal material, standard decoction and formula granules.

The present invention addresses the problem of reducing the bitterness and / or astringency of a wood component in an alcoholic beverage. In the present invention, the pH and acidity of an alcoholic beverage are set to within specific ranges. The bitterness or the astringency caused by at least one compound selected from the group consisting of gallic acid, syringic acid, vanillin, and syringaldehyde can be reduced.

The invention discloses a syringic acid-based acute graft-versus-host disease prediction and use method, and belongs to the technical field of biological medicine.The syringic acid-based acute graft-versus-host disease prediction and use method comprises the steps that the occurrence and prognosis of aGVHD after transplantation are predicted by detecting the syringic acid level in an allo-HSCT patient, and reduction of the syringic acid level in the patient indicates increase of the aGVHD occurrence risk and poor prognosis; comprising the steps of giving an effective dose of syringic acid, inhibiting T cell activation and inflammatory factor secretion, relieving aGVHD symptoms, prolonging the survival time of an aGVHD model animal and improving target organ injury, and the diagnosis and prediction value of syringic acid in aGVHD occurrence and clinical prognosis is evaluated through a clinical sample. The application of syringic acid in prevention and treatment of aGVHD by inhibiting T cell function and inflammatory factor secretion is explored through in-vitro and animal experiment research, and the technical effects of helping clinicians to timely discover high-risk patients, formulate intervention measures in advance, improve prognosis of the patients and improve the treatment effect are achieved.

The invention discloses a method for rapidly determining various phenolic acid substances in a fermentation product, and belongs to the technical field of detection. The determination method comprises the following steps: 1. Taking a to-be-detected substance, and extracting phenolic acid substances in the to-be-detected substance through an alcohol precipitation-SAX solid-phase extraction combined technology to obtain a to-be-detected sample; analyzing the to-be-detected sample by adopting ultra-high performance liquid chromatography tandem triple quadrupole mass spectrometry to obtain the content of the target substance in the to-be-detected substance; the target substance is a non-volatile phenolic acid substance. Accurate quantification of trace and trace caffeic acid, dihydrocaffeic acid, ferulic acid, chlorogenic acid, gallic acid, vanillic acid, syringic acid, p-coumaric acid, salicylic acid and (+ / -)-catechin in fermentation products within 8-15 min is achieved by combining impurity removal and concentration pretreatment with ultra-high performance liquid chromatography tandem triple quadrupole mass spectrometry. According to the method, the pretreatment mode is convenient to operate, the detection process is fast, and the detection result is accurate.

The invention belongs to the technical field of acne rosacea treatment, and discloses a preparation method and application of a composition for treating acne rosacea, the composition for treating acne rosacea contains a moutan bark extract and a coptis chinensis extract, and also contains a lucid ganoderma extract, a cinnamon extract, paeoniflorin and syringic acid. The inflammatory response of rosacea is closely related to the expression of two core inflammatory factors, namely TNF-alpha and TLR4, and the invention consciously aims at the TLR4-TNF-alpha inflammatory axis multi-target design, inhibits the expression of TLR4 and TNF-alpha, and blocks the'start-amplification 'chain of inflammation, thereby inhibiting the recurrence of inflammation. In addition, the composition for treating rosacea provided by the invention can also improve capillary dysfunction, effectively inhibit microbial growth, and prevent and treat rosacea from multiple dimensions.

The invention provides syringic acid as well as preparation, a pharmaceutical composition and medical application thereof. The purity of the syringic acid is 95% or above, and the syringic acid can be extracted from motherwort. The syringic acid disclosed by the invention has a good dissolving effect on fibrin in thrombus formation, is relatively high in blood-brain barrier transmittance, has thrombus dissolving and antithrombotic effects, and can be used for preparing medicines for treating thrombotic diseases. The syringic acid can be processed into oral preparations such as tablets, capsules, granules, dripping pills and other common preparations or sustained release preparations, injection preparations such as injection freeze-dried powder injections, and external preparations such as ointments or emulsifiable paste according to a conventional production process of pharmaceutics, and is used for treating thrombotic diseases, especially cerebral thrombosis diseases.

The invention provides an electrochemical method for pairwise synthesizing syringic acid and adiponitrile. The method comprises the following steps: 1) mixing syringaldehyde, an alkaline electrolyte, an alcohol solvent, an alkyl glycoside surfactant and water, and adding the mixture into an anode chamber of an electrolytic cell; (2) acrylonitrile, phosphate, borate, a quaternary ammonium base surfactant and water are mixed and added into a cathode chamber of the electrolytic cell; and 3) heating the electrolyte in the cathode chamber and the anode chamber of the electrolytic cell, then carrying out an electrolytic reaction, carrying out electrochemical oxidation on syringaldehyde at the anode to synthesize syringic acid, enabling hydrated hydrogen ions to enter the cathode chamber across a membrane, and synthesizing adiponitrile with acrylonitrile at the cathode. The syringic acid synthesis method is clean, environmentally friendly and low in cost, meanwhile, the problem of anode corrosion in the operation process of electrosynthesis of adiponitrile is solved, and the tail gas safety risk caused by oxygen evolution of an anode for synthesis of adiponitrile is eliminated. The method has the advantages of simple steps, high total product yield, low equipment investment, low operation risk, mild reaction conditions, less three wastes and low energy consumption, and is suitable for wide industrial application.

The invention belongs to the technical field of insulating oil additives, and discloses a preparation method and application of octyl syringate. The preparation method of the octyl syringate comprises the following steps: (1) mixing syringic acid, n-caprylic alcohol and a first catalyst, and reacting; the first catalyst is at least one of phosphotungstic acid, boron tungstic acid, silicotungstic acid and molybdophosphoric acid; and (2) adding a molecular sieve and a second catalyst, and reacting again. The octyl syringate prepared by the preparation method disclosed by the invention can be used as an insulating oil additive to be applied to insulating oil, so that the insulating oil is effectively protected, the service life of the insulating oil is prolonged, the performance reduction caused by aging oxidation is reduced, the oxidation stability of the insulating oil is improved, the volatility of the insulating oil under a high-temperature condition is reduced, and the flash point of an oil product is improved; therefore, the insulating oil is not easy to cause fire or explosion accidents at high temperature, and meets the requirements of electrical equipment insulating oil with higher standards.

The present invention relates to stabilisers based on syringic acid, vanillic acid, isovanillic acid or 5-hydroxyveratric acid, plastic composition. The invention also relates to a method for stabilising a plastic composition and a stabiliser composition having a high stabilising effect.

The invention provides a drug-drug co-amorphous substance co-carrying analgesic active components of syringic acid and rotundine. The prescription of the drug-drug co-amorphous substance does not contain any carrier or auxiliary material, the preparation method is simple, convenient and efficient, special processes and equipment are not needed, the cost is low, and industrialization is easy. The co-amorphous substance prepared by the invention not only can significantly improve the water solubility of syringic acid and rotundine, but also can improve the transdermal performance of drugs, and is beneficial to development of double-drug co-loaded efficient oral or external compound products.