2307 results about "Carbonyl group" patented technology

The invention discloses a high-performance carbonyl reductase mutant and application thereof in synthesis of a series of chiral alcohols. The high-performance carbonyl reductase mutant is obtained by performing the following mutations on an amino acid sequence as shown in SEQ ID NO.2: the 69th alanine mutates into any one of lysine, leucine, aspartic acid or asparagine, and the 69th alanine mutates into any one of lysine, leucine, aspartic acid or asparagine; and / or the 100th glycine is mutated into any one of glutamic acid, serine, lysine or asparagine. Compared with a wild type enzyme, the thermal stability and the catalytic activity of the obtained mutant are remarkably improved, particularly, single point mutants Mut-A69N, Mut-G100E and Mut-G100N and a combined mutant Mut-A69N-G100N show excellent relative enzyme activity, thermal stability and substrate tolerance. The mutant has high catalytic activity and stability to various chiral alcohols, and the contradiction that the traditional carbonyl reductase is easy to inactivate at high temperature and the catalytic efficiency is difficult to achieve at the same time is solved. The invention provides an efficient and stable enzyme catalysis tool for green biological preparation of chiral drug intermediates.

Provided is a polyamide resin, which is a copolymer of a biodegradable polyamide, such as polyamide 2 to polyamide 4, and another polyamide, the polyamide resin having enhanced biodegradability. The polyamide resin contains a structural unit represented by Formula (1) and another polyamide structural unit, and a difference between a degree of randomness determined based on a proportion of each structural unit as determined by 1H-NMR measurement when structural units are assumed to have an ideal random sequence and a degree of randomness determined based on a proportion of carbonyl carbon of an amide group linking different structural units with respect to a total peak integrated value for carbonyl carbon as determined by 13C-NMR measurement is 0.10 or less, where in Formula (1), x is an integer of 1 or greater and 3 or less.

The invention belongs to the technical field of antibiosis and wound healing promotion, and relates to double-response (near-infrared light and hydrogen peroxide double-response photo-thermal / carbon monoxide therapy) antibacterial hydrogel as well as preparation and application thereof. The invention relates to a double-response antibacterial hydrogel. The antibacterial hydrogel is prepared from the following components: drug-loaded nano particles and a hydrogel matrix. The drug-loaded nano particles are prepared by loading dimanganese decacarbonyl (MnCO) into cavities of hollow mesoporous copper sulphide nano particles (HMCuS NPs) and coating the surfaces of the particles with a polydopamine layer (PDA). According to the invention, CO / PTT synergistic treatment of bacterial infected wounds is realized, and the antibacterial effect is significantly improved. An in-vitro antibacterial experiment result shows that the antibacterial hydrogel shows extremely strong inhibition capability on escherichia coli and staphylococcus aureus, and the problem of drug resistance caused by a bacterial biofilm is effectively solved.

The invention discloses a preparation method of a grafted and substituted thiophene polymer material, which comprises the following steps: mixing poly (3-hexylthiophene), a grafting monomer, a catalyst and an auxiliary agent, and heating for reaction to obtain the grafted and substituted thiophene polymer material, the structural formula of the grafting monomer is as shown in formula (I); wherein B is fluorine, chlorine, bromine or iodine, A is a carbon atom or a nitrogen atom, and R is cyano, formyl, methoxycarbonyl or; according to the method, pre-synthesis of complex functional monomers is avoided, the main chain of the poly (3-hexylthiophene) can be directly modified without using an expensive catalyst or ligand, the polymerization reaction of the poly (3-hexylthiophene) is not interfered, and meanwhile, the method has the advantages of simplified steps and low cost.

The invention belongs to the technical field of organic radiation luminescence and radiation imaging, and discloses an aggregation-induced delayed fluorescence (AIDF) type organic scintillator material and a preparation method thereof, and a preparation method and application of a flexible organic scintillation film. The molecular structure of the material comprises carbonyl, methylene, sulfuryl and other connecting units, phthalonitrile is used as an acceptor unit, carbazole is used as a donor unit, an aggregation-induced excitation state is formed through space charge transfer among molecules, efficient AIDF luminescence and large Stokes shift characteristics are realized, the self-absorption phenomenon is effectively avoided, and the luminescent efficiency is improved. The X-ray fluorescence probe is suitable for a luminescence process under an X-ray excitation condition, the sensitivity of X-ray detection is remarkably improved, and the lowest detection limit can reach 276nGy.s <-1 > and is far superior to the 5.5 mu Gy.s <-1 > standard required by medical diagnosis. Besides, the flexible scintillator film prepared based on the material system radiates and emits light within the waveband range of 450-750 nm and is perfectly matched with the response area of a silicon-based detector, X-ray imaging with the high signal-to-noise ratio is achieved, and the imaging resolution is as high as 20.01 lp.mm <-1 >.

The invention provides a carbonyl reductase mutant and application thereof in preparation of chiral alcohol compounds, and belongs to the technical field of gene engineering and enzyme catalysis. According to the invention, on the basis of the wild carbonyl reductase, the mutant with activity obviously superior to that of the wild carbonyl reductase is obtained through specific mutation, the selectivity and stability of the enzyme are improved, and the mutant has a wide application prospect in catalytic synthesis of chiral alcohol compounds.

The invention discloses a carbonyl reductase mutant as well as a preparation method and application thereof, and belongs to the technical field of gene engineering and enzyme engineering. According to the invention, wild-type carbonyl reductase of Stachybotrys chlorohallonata is taken as an evolution template, and a plurality of mutants with catalytic activity, thermal stability and substrate spectrum obviously superior to those of the wild-type carbonyl reductase are obtained through an enzyme engineering technology. The carbonyl reductase mutant can catalyze various prochiral carbonyl compounds to obtain chiral alcohol with high stereoselectivity (ee is greater than 99%). The carbonyl reductase mutant provides a novel, efficient and environment-friendly technical route for industrial production of chiral alcohol products, and has very high industrial application potential.

The invention discloses a high-stability carbonyl reductase mutant and application of the high-stability carbonyl reductase mutant in chiral alcohol synthesis. An amino acid sequence as shown in SEQ ID NO.2 is mutated as follows: 20th leucine is replaced by any one of lysine, threonine, aspartic acid or isoleucine, and / or 55th leucine is replaced by any one of methionine, serine, lysine or isoleucine, and / or 55th leucine is replaced by any one of methionine, serine, lysine or isoleucine. Compared with a wild type enzyme, the stability of the obtained mutant is remarkably improved, particularly, single-point mutants Mut-L20I and Mut-L55I and a combined mutant Mut-L20I-L55I show excellent relative enzyme activity, thermal stability and substrate tolerance. The mutant has high catalytic activity and stability to various chiral alcohols, has the advantages of high catalytic efficiency, high thermal stability, strong substrate tolerance, easiness in fermentation production and the like, and is suitable for industrial application of enzymatic synthesis of chiral alcohols.

The invention relates to the technical field of biological medicines, and particularly discloses a BODIPY (boron dipyrromethene)-based compound and an application of the BODIPY-based compound in photodynamic oxidation of beta-amyloid protein (Abeta). The compound takes iodo-BODIPY as a photosensitive core and is connected with 4-t-butyloxycarboryl benzene as an A beta recognition group. The introduction of iodine atoms significantly enhances the intersystem crossing ability of molecules, so that the molecules have excellent reactive oxygen species (ROS) generation ability. The compound has high ROS yield, good optical stability and biocompatibility, can specifically target A beta aggregate, realizes photodynamic oxidative degradation, and provides a novel potential tool for treatment of Alzheimer's disease.

The present invention provides a production method of a thienopyrimidine derivative or a salt thereof which has a gonadotropin releasing hormone (GnRH) antagonistic action with high quality in high yield. The present invention provides a method of producing a thienopyrimidine derivative, which comprises reacting 6-(4-aminophenyl)-1-(2,6-difluorobenzyl)-5-dimethylaminomethyl-3-(6-methoxypyridazin-3-yl) thieno[2,3-d]pyrimidine-2,4 (1H,3H)-dione or salt thereof, 1,1′-carbonyldiimidazole or a salt thereof and methoxyamine or a salt thereof, and the like.

The invention discloses a progesterone 5beta-reductase mutant and application thereof in synthesis of 5beta-dihydrosteroid, relates to the technical field of biology, and in particular relates to application of gene mining and engineering modification of progesterone 5beta-reductase derived from bacteria in asymmetric synthesis of 5beta-dihydrosteroid. According to the progesterone 5 beta-reductase LpP5beta R disclosed by the invention, the progesterone 5 beta-reductase LpP5beta R from bacteria psoromais is obtained by a gene mining method, and the progesterone 5 beta-reductase LpP5beta R can be subjected to soluble expression in escherichia coli. The mutant obtained by mutating the wild type LpP5beta R has obviously improved catalytic ability on progesterone, and can efficiently catalyze delta 4-3-carbonyl steroids such as hydrocortisone, dinorcitol and the like to generate corresponding 5beta-dihydrosteroids. According to the invention, the technical bottlenecks of poor heterologous expression and low catalytic efficiency of plant-derived progesterone 5beta-reductase are solved, and a potential biocatalyst is provided for green manufacturing of 5beta-dihydrosteroid drugs.

The invention discloses a peracetylated polysaccharide derivative mixing accelerator as well as a preparation method and application thereof, and relates to the technical field of polysaccharide derivatives. Alkyl polyglucoside and glycidyl ether are subjected to etherification reaction to obtain polysaccharide derivatives; and adding acetic anhydride and an organic weak base catalyst into the polysaccharide derivative, and carrying out esterification reaction to obtain the peracetylated polysaccharide derivative. The obtained peracetylated polysaccharide derivative can be used for reducing the minimum miscible pressure of CO2 in an offshore oilfield. The polysaccharide derivative provided by the invention is simple in synthesis process, and the molecular activity of the polysaccharide derivative can be regulated and controlled by changing the number of carbon dioxide-philic groups and the length of oleophylic unsaturated hydrocarbon chains, so that the polysaccharide derivative can be used in the CO2 oil displacement process of oilfield exploitation, and the minimum miscible pressure in the CO2 oil displacement process is effectively reduced.

The invention discloses a soil-plant carbon element tracking method and system based on isotope labeling, particularly relates to the technical field of soil carbon cycle in-situ detection, and is used for solving the technical problem that a carbon migration path in a rice rhizosphere heterogeneous micro region cannot be distinguished in the prior art. The method comprises the following steps: arranging a spatial coding microprobe array on a rice root system and a soil interface of a rice field, synchronously applying a C13 labeled compound, and continuously obtaining a grid node oxidation-reduction potential and a carbon isotope abundance value; dividing the boundary of a root surface oxidation layer and an anaerobic layer based on day and night oscillation phase difference mutation; detecting peak displacement migration from carbonyl bonds to carbon-carbon bonds in a boundary transition region by adopting an in-situ Raman spectrum, and correcting a space boundary; partitioning and clustering carbon isotope abundance values according to the corrected boundary, and identifying hot spot boundaries of a root tip secretion active region, a microorganism enrichment region and a mineral binding region; calculating the carbon isotope flux gradient in each region and generating a spatial distribution map; in-situ analysis of a rhizosphere carbon migration path is realized, and rice field carbon cycle research precision is improved.

The invention discloses a reversible cross-linked paper coating and a repulping switching process, and belongs to the technical field of paper coatings. The coating is composed of an acrylate emulsion, a polyhydroxyalkanoate dispersion and a dynamic cross-linking system, wherein the system is one of carbonyl-hydrazine, imine, Diels-Alder, ester exchange, borate or polyvalent metal-carboxylate. The coating is coated with 6-15 g / m, the use state is that Cobb60 is smaller than or equal to 18 g / m, Kit is larger than or equal to 10, WVTR is smaller than or equal to 80 g / (m.d) at the temperature of 38 DEG C and the RH of 90%, OTR is smaller than or equal to 200 cm / (m.d) at the RH of 23 DEG C / 80%, the initial sealing temperature is smaller than or equal to 180 DEG C, and the sealing strength is larger than or equal to 6.0 N / 15 mm. In the re-pulping stage, net releasing is triggered through alkali, acid (containing CO2 injection), a chelating agent or ultrasonic assistance, and according to CEPI V3 / PTS-RH 021: 2012, the fiber recovery rate is measured to be larger than or equal to 98%, the coarse slag rate is measured to be smaller than or equal to 1.0%, and the adhesion matter is measured to be smaller than or equal to grade 1. The formula does not contain PFAS, and high bio-based carbon content can be realized.

The invention discloses a dicarbonyl cyclopentadienyl cobalt complex as well as a preparation method and application thereof, and belongs to the technical field of organic metal synthesis. The preparation method of the dicarbonyl cyclopentadienyl cobalt complex specifically comprises the following steps: (1) dissolving cobalt octacarbonyl in carbon monoxide pre-saturated dichloromethane, and continuously introducing carbon monoxide gas for protection to obtain a reaction system; (2) dissolving cyclopentadiene in dichloromethane, and continuously introducing carbon monoxide gas for protection to obtain a cyclopentadiene solution; (3) adding a cyclopentadiene solution into the reaction system, heating and stirring for reaction; and (4) carrying out pressurized distillation and rectification on the reaction system. According to the invention, the carbon monoxide protective gas is introduced and the cyclopentadiene solution is prepared in the whole process to reduce the decomposition of the raw materials and reduce the generation of byproducts, so that the subsequent purification difficulty is reduced, and the reaction yield and the economic benefit of the product are improved.

The invention discloses a halide solid electrolyte with a multilayer hierarchical core-shell structure, which sequentially comprises an inner core halide solid electrolyte, a first conductive polymer high-molecular coating layer and a second hydrophobic polymer high-molecular coating layer from inside to outside, the first conductive polymer high-molecular coating layer is formed by copolymerizing conductive polymer monomers with ether oxygen groups-O-or carbonyl C = O, and the second hydrophobic polymer high-molecular coating layer is prepared by ball-milling, sintering and coating a high-molecular hydrophobic material on the surface of the first conductive polymer high-molecular coating layer; and a chemical bonding interface is formed between the first conductive polymer high-molecular coating layer and the inner core halide solid electrolyte through an ether oxygen group-O-or carbonyl C = O in a molecular chain segment. The thickness of the prepared halide solid electrolyte membrane can be reduced to be less than 100 microns, the growth of lithium dendrites is inhibited by the interface self-adaptive characteristic, and the capacity retention rate is gt after 200 cycles; 80%; the sintering temperature is less than or equal to 300 DEG C, the energy consumption is reduced, and lattice distortion is avoided.

The application provides a leaching agent for removing thallium and beryllium in lithium residue and application. The leaching agent comprises a first leaching agent and a second leaching agent. The first leaching agent is an organic acid solution, the organic acid comprises a carboxyl group, and at least one of a hydroxyl group, a sulfhydryl group, a carbonyl group and a sulfonic acid group; the organic acid is a single organic acid or a mixed organic acid; the second leaching agent comprises a cation agent and a reducing agent, the cation agent can form at least one of K + , NH4 + , Mg 2+ , Na + , Fe 3+ in an aqueous solution, and the reducing agent comprises an inorganic reducing agent and / or an organic reducing agent. The organic acid in the first leaching agent can destroy the crystal structure of the lithium residue, and the groups such as the carboxyl group and the hydroxyl group can complex thallium and beryllium ions to make them more easily leached out. On this basis, the cation and the reducing solution in the second leaching agent accelerate the release of thallium and beryllium through ion exchange and reduction. The above leaching agent can remove thallium and beryllium in the lithium residue at the same time, and has a high removal rate of thallium and beryllium.

The invention provides a magnetic resin composition, a magnetic film and application thereof. The magnetic resin composition comprises (A) a magnetic filler, (B) epoxy resin, (C) a curing agent and (D) a flexibilizer, the magnetic filler (A) comprises carbonyl iron powder (A1), FeSiCr alloy (A2) and iron-based nanocrystals (A3); based on the total mass of the magnetic resin composition as 100%, the content of the (A) magnetic filler is 85% or more; based on 100% of the total mass of the magnetic filler (A), the content of the carbonyl iron powder (A1) is 55%-65%, the content of the FeSiCr alloy (A2) is 15%-25%, and the content of the iron-based nanocrystalline (A3) is 15%-25%. According to the magnetic resin composition and the preparation method thereof, specific types of magnetic fillers are introduced and compounded according to a specific content, so that the magnetic resin composition has relatively high magnetic conductivity and relatively low magnetic loss after being cured, and meanwhile, the binding force with a copper layer is relatively high.

The invention discloses a preparation method of a biomass hard carbon negative electrode material, which is characterized by comprising the following steps: carrying out primary carbonization on a biomass material, sequentially introducing a phosphorus element, a boron element and a copper element, carrying out secondary carbonization on a modified hard carbon raw material, and introducing carbonyl to obtain the hard carbon negative electrode material. Preliminary carbonized powder, boric acid and phosphoric acid are added into a reaction kettle together for a low-temperature graphitization reaction, phosphorus and boron are introduced for a hard carbon raw material, the phosphorus can widen the spacing of a graphite layer, the boron can catalyze rearrangement of a graphitized carbon layer, then the hard carbon raw material and organic copper salt are mixed and ground in cooperation, secondary carbonization is conducted, and the hard carbon material is obtained. By introducing the copper element, graphitization of the product can be promoted, and meanwhile, copper atoms can also improve the conductivity; and glyoxylic acid is added to introduce carbonyl into the product, and the carbonyl can preferentially catalyze decomposition of the inorganic salt, so that decomposition of an organic solvent is inhibited, and then a uniformly distributed inorganic salt-rich SEI film is formed.

The invention relates to a toughened modified epoxy resin material and a preparation method thereof, and belongs to the technical field of high polymer materials. The toughened modified epoxy resin material comprises the following components in parts by weight: 90-120 parts of epoxy resin, 8-25 parts of a curing agent, 1-3 parts of a diluent, 0.5-5 parts of a curing accelerator, 4-18 parts of graphite, 5-15 parts of a modified toughening agent and 1-5 parts of a modified flame retardant, in the modified flexibilizer, a benzene ring and carbonyl of a polyimide structure endow the material with excellent heat resistance, intertwining between chains is avoided, embrittlement is avoided, the material and polyurethane are synergistically toughened, and a flexible-Si-O-Si-chain segment relieves thermal stress generated in the resin and improves the tensile strength; benzoxazine in the modified flame retardant contains a nitrogen element, releases non-combustible gas during combustion, forms a carbon layer at high temperature and covers the surface of the material, so that the flame retardance is improved; the toughened and modified epoxy resin material prepared by the invention not only has good toughening and heat-resisting effects, but also has an excellent flame-retardant effect.

Methods for treating patients with wAIHA comprising administering at least one compound chosen from (R)-2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile (rilzabrutinib) and pharmaceutically acceptable salts thereof are disclosed.

The invention relates to the technical field of compound preparation and medicine, in particular to a boron atom-labeled compound for targeting fibroblast activating protein as well as a preparation method and application of the boron atom-labeled compound. The preparation method comprises the following steps: carrying out acid amine condensation on (4-(((2, 5-dioxopyrrolidine-1-yl) oxy) carbonyl) phenyl) boric acid and an FAP targeting ligand to obtain a boron atom-labeled compound targeting the fibroblast activating protein; and the FAP targeting ligand is FAPI-46 or FAP-2286 (Fibroblast Amplified Polymorphism). The compound is easy to prepare, high in purity and good in stability, the content of boron atoms in tumor tissue can be greatly increased, and a treatment basis is provided for boron neutron capture therapy.

The application provides an electrolyte additive, an electrolyte and a battery, wherein the electrolyte additive comprises an indole group, a carbonyl group, a fluorine atom, a siloxane group and a boron atom, so that the electrolyte additive can combine with silicon particles to form a stable structure, form a stable SEI film, reduce decomposition of the electrolyte, improve electronic conductivity and reduce occurrence of electrolyte side reactions, thereby effectively inhibiting expansion of a silicon-carbon negative electrode, solving problems of low initial efficiency, poor cycle performance and poor high-temperature storage performance of the silicon-carbon negative electrode, and improving cycle performance and high-temperature storage performance of the battery.

The invention provides a preparation method of a (S)-5-(2, 2-dimethyl tetrahydro-2H-pyran-4-yl)-N-methyl-N-phenyl-1H-indole-2-formamide compound, which comprises the following steps: by taking a compound 1 as an initial raw material, reacting the compound 1 with a boric acid ester reagent to obtain a boric acid ester compound 2; the method comprises the following steps: by taking a compound 3 as an initial raw material, reducing carbonyl through enzyme catalysis to obtain a compound 4, then protecting alcoholic hydroxyl through a sulfonylation reagent to obtain a compound 5, and finally, directly coupling the compound 5 with a compound 2 under the action of a catalyst to obtain a target product compound 6. The whole process is low in experimental condition requirement, simple to operate, high in yield and suitable for process amplification.

The invention discloses a passivation molecule, the passivation molecule is N-acetyl piperazine halide and N-formyl piperazine halide, the two ends of the passivation molecule respectively contain ammonium cations and carbonyl functional groups, and the passivation molecule shows stable plane orientation preference due to the double-site geometric synergistic anchoring effect of'ammonium-carbonyl '. Therefore, synchronous passivation of double defects can be realized on the surface of the perovskite, and the photoelectric conversion efficiency and the stability of the perovskite solar cell can be improved.

To provide an inkjet ink that enables formation of an image having excellent color developability and excellent storage stability.SOLUTION: An inkjet ink comprises a pigment, a dispersant, and water, wherein the dispersant is a copolymer of a monomer mixture comprising ω-carboxy-polycaprolactone monoacrylate, polyalkylene glycol (meth)acrylate, and a vinyl monomer comprising at least one selected from the group consisting of an aromatic group and a β-dicarbonyl group.SELECTED DRAWING: None

The invention relates to the technical field of acid tail gas treatment, and discloses a boron-nitrogen-doped aluminum oxide catalyst as well as a preparation method and application thereof. The method comprises the following steps: (1) mixing an aluminum source, a nitrogen source, a boron source and water to obtain a mixed solution, then adding a peptizing agent to adjust the pH of the mixed solution to be acidic, and then standing and aging; (2) drying the material subjected to standing and aging in the step (1), then roasting under protective gas, and then sequentially carrying out high-temperature nitriding and cooling; and (3) carrying out plasma treatment on the material cooled in the step (2). The catalyst prepared by the method has large specific surface area and catalytic activity, can well capture water and carbonyl sulfide, converts carbonyl sulfide into hydrogen sulfide and improves the purity and yield of enriched hydrogen sulfide, and the preparation method of the catalyst is simple and efficient.

To produce and provide a resin sheet having superior processability using a predetermined acrylic resin.SOLUTION: A resin sheet is obtained by kneading 10 wt.% to less than 40 wt.% of an acrylic resin having a polymerization degree of 1000-20000 and more than 60 wt.% to 90 wt.% of a carbonyl-group-containing polymer.SELECTED DRAWING: Figure 3

Provided are: a gas barrier film that includes a vapor deposition layer (B) that includes at least one metal element selected from among zinc, magnesium, and calcium and a compound that has a carbonyl group on a plastic film; and a packaging body that includes the gas barrier film. The peak ratio (A1575 / A1687) of the absorption peak height A1687 at a wavenumber of 1687 cm-1 to the absorption peak height A1575 at a wavenumber of 1575 m-1 on an infrared absorption spectrum for the vapor deposition layer (B) is preferably 0.1–5.0.

The invention belongs to the technical field of flame-retardant master batches, and particularly relates to a flame-retardant master batch for polypropylene and a preparation method thereof.The preparation method comprises the steps that tris (2-hydroxyethyl) isocyanurate is heated and molten, tetrabutyl titanate and DOPO-DPP are added into the molten tris (2-hydroxyethyl) isocyanurate, the mixture reacts for 3-4 h, melamine and cyanuric acid are added into the molten tris (2-hydroxyethyl) isocyanurate, the mixture reacts for 30 min, cooling and smashing are conducted, and a macromolecular flame retardant TDMC is obtained; the preparation method comprises the following steps: carrying out ester exchange reaction on 2, 4-diphenyl-6-[2-hydroxy-4-(ethoxycarbonyl methoxy) phenyl]-1, 3, 5-triazine and 2, 2, 6, 6-tetramethyl piperidinol to prepare a free radical capturing agent; the polypropylene, the TDMC, the free radical scavenger and the zeolite are put into a high-speed mixer to be stirred and mixed, and then extrusion granulation is performed. The macromolecular flame retardant TDMC is adopted, the molecular weight of the macromolecular flame retardant TDMC is large, the water resistance is good, and the compatibility and damp-heat stability of the flame-retardant master batch in polypropylene are improved.