394 results about "Uracil" patented technology

Provided herein are engineered variants of archaeal polymerases that exhibit exonuclease-minus activity, enhanced thermostability, enhanced incorporation of 3′ modified nucleotides, improved uracil-tolerance and / or reduce sequence-specific errors in polymerase-catalyzed nucleotide binding and extension reactions relative to wild type polymerase enzymes. Also provided are uses of the engineered polymerases for forming complexed polymerases and forming binding complexes, and uses for conducting nucleic acid sequencing reactions.

The invention relates to the technical production field of metabolic engineering and genetic engineering, and particularly provides a uracil production strain as well as a construction method and application thereof. According to the strain, a uridine kinase gene udk is knocked out on an E.coli W3110 genome, and meanwhile, a T7RNA polymerase gene is integrated; the uridine monophosphate kinase gene pyrH is weakened; the method comprises the following steps: overexpressing a carbamyl phosphate synthetase gene carAB, a ribose phosphate pyrophosphate kinase gene prsA, a pyrimidine-5 '-nucleoside enzyme gene ppnN, UMP phosphohydrolase genes umpH and umpG, a ribonucleoside hydrolase 1 gene rihA and a glutamine synthetase gene glnA; an orotic acid nucleoside monophosphate decarboxylase gene pyrF and an orotic acid ribosyltransferase gene pyrE of wild type bacillus subtilis B.subtilis 168 are introduced in a heterologous manner, so that an orotate nucleoside monophosphate decarboxylase gene pyrF and an orotate ribosyltransferase gene pyrE are obtained. The safe, efficient and low-cost production of the uracil is realized.

The invention belongs to the technical field of microbial medicine, and provides a primary multidrug resistance human far-end bile duct cancer cell line CBC3T-6 Homo sapiens and application thereof.The human far-end bile duct cancer cell line CBC3T-6 Homo sapiens is separated from differentiated adenocarcinoma in a far-end bile duct, the human far-end bile duct cancer cell line CBC3T-6 Homo sapiens is already subcultured to 50 generations at present, the long-term in-vitro culture character is stable, and on the premise that the biological characteristics of bile duct cancer are reserved, the human far-end bile duct cancer cell line CBC3T-6 Homo sapiens can be used for preparing the primary multidrug resistance human far-end bile duct cancer cell line CBC3T-6 Homo sapiens. The compound has the characteristics of short multiplication time, high mouse subcutaneous tumor formation rate and the like, and has different degrees of drug resistance to gemcitabine, 5-fluorouracil, oxaliplatin and cis-platinum in first-line anti-cancer drugs for bile duct cancer. The method not only enriches an extrahepatic bile duct cancer cell bank, provides a new cell model for basic research and clinical drug research and development of bile duct cancer, but also provides powerful scientific research data for research developed based on the genetic background of Chinese population. Therefore, the primary multidrug resistant cell line has higher scientific research and clinical application values.

The invention belongs to the technical field of biomedicine, and discloses a Parkinson's disease specific plasma metabolism marker and application thereof.The plasma metabolism marker comprises uracil, kynurenine, phenolsulfonic acid, p-cresol, di-high gamma-linolenic acid, atorvastatin, 2-methoxybenzoic acid, carabicycline, nitrogen hydroxyl 2-amino-3, 5-di-tert-butyl-3, 5-di-tert-butyl-3, 5-di-tert-butyl-3, 5-di-tert-butyl-3, 5-di-tert-butyl-3, 5- The invention relates to an anti-inflammatory agent which is prepared from 2, 8-dimethylimidazo quinoxaline, dihydroxy phenethyl alcohol O-sulfate, racemization-4-hydroxy-4-O-(beta-D-glucuronate)-all-trans retinol acetate, fructosyl valine, thiaxanthene and acetylpyridine methanol. It is proved for the first time that the 14 plasma metabolites are associated with the Parkinson's disease, a Parkinson's disease prediction method is constructed based on the markers, the prediction result is reliable, and a new way is provided for diagnosis of the Parkinson's disease.

Provided herein are engineered variants of archaeal, prokaryotic, and eukaryotic polymerases that exhibit enhanced thermostability, enhanced incorporation of 3′ modified nucleotides, and improved uracil-tolerance, in polymerase-catalyzed nucleotide extension reactions relative to wild type polymerase enzymes. Also provided are uses of the engineered polymerases for forming complexed polymerases, forming binding complexes and forming ternary complexes, and uses for conducting nucleic acid sequencing reactions.

The invention provides a uracil production strain and a construction method and application thereof.According to the strain, on an E.coli UR14 genome by means of a CRIPSR / Cas9 gene editing technology, firstly, psuG genes, preTA genes, rutA genes and upp genes are knocked out, so that decomposition of uracil is blocked; then, a uridine phosphorylase gene udp and a pyrimidine-5 '-nucleotide nucleotidase gene ppnN are subjected to overexpression, and synthesis and accumulation of uracil are synergistically enhanced; and finally, overexpression of the ribose phosphate mutase gene pgm further enhances the conversion of a by-product ribose phosphate 1-precursor 5-ribose phosphate 1-pyrophosphate and improves the carbon utilization rate, and the obtained strain has good genetic stability and high fermentation yield, can stably produce uracil, and has wide application prospects.

To provide a nucleic acid having reduced cytotoxic activity and enhanced protein production, a pharmaceutical composition comprising the nucleic acid, and a method of producing the nucleic acid.SOLUTION: Provided are: a nucleic acid including a protein-encoding region that has been modified, wherein the total proportion of uracil residues and adenine residues in the modified protein-encoding region is reduced in comparison to that in the protein-encoding region prior to modification; and a method of producing the nucleic acid.SELECTED DRAWING: None

The invention discloses a genetically engineered bacterium for producing pseudouridine and a construction method of the genetically engineered bacterium, escherichia coli W3110 is used as a starting strain, the supply of precursor substances including aspartic acid, carbamyl phosphoric acid, glutamine and 5 '-phosphoribosyl pyrophosphate prpp is enhanced, pyrimidine nucleoside synthesis operon from bacillus subtilis is introduced, and the pseudouridine is produced. The invention discloses a pseudouridine-5 '-phosphosidase gene psuG and a preparation method thereof, and relates to the field of microorganisms, the field of genetic engineering and the field of fermentation engineering. The pseudouridine-5'-phosphosidase gene psuG is expressed by using high-copy plasmids, and the application of the pseudouridine-5 '-phosphosidase gene psuG to preparation of the pseudouridine-5'-phosphosidase gene psuG is provided. The strain is fermented in a 50L fermentation tank for 60h, the yield of pseudouridine reaches 50.8 g / L, the conversion rate is 18%, which is the highest value reported at present, and the strain has high industrial production value.

The invention relates to an aqueous adhesive composition, comprising a thermosetting resin based on: - at least one aromatic compound A1 comprising at least one aromatic ring bearing at least two functions, one of these functions being an aldehyde function or a hydroxymethyl function, the other being an aldehyde function or a hydroxymethyl function; - at least one aromatic polyphenol A2 comprising at least one aromatic ring bearing at least two hydroxyl functions in the meta position relative to one another, the two positions ortho to at least one of the hydroxyl functions being unsubstituted; and a compound (III): R3NH-C=X-N(R1R2) in which each group R1, R2, R3 represents, independently of one another, an alkyl, alkenyl, aryl, arylalkyl, alkylaryl or cycloalkyl group or hydrogen, X represents S, O or N-R4 with R4 representing an alkyl, aryl, arylalkyl, alkylaryl or cycloalkyl group or compound (III) is melamine or uracil; with compound (I) being at a weight content of solids of the aqueous adhesive composition ranging from 0.003 to 0.160.

The invention belongs to the field of variation or genetic engineering, and discloses a plant C-to-K base editor. The technical problem to be solved by the invention is how to realize C-to-K base editing in plants. The invention discloses a basic group editor for plant C to K. The basic group editor contains a Cas protein and uracil DNA glycosylase, wherein the amino acid sequence of the uracil DNA glycosylase is 20th to 244th sites of SEQ ID No.2. Experiments prove that the base editor provided by the invention realizes targeted C-to-K editing with base editing efficiency as high as 66.66%, and the range of the base editor is widened. The base editor opens up a way for optimizing crop traits (such as disease resistance, drought resistance and yield) by accurately solving mononucleotide variation affecting plant traits.

Described herein are methods, compositions, and kits for removing false positive uracils due to the deamination of unmethylated cytosines in assays using engineered cytosine deaminases to deaminate methylated cytosines. The methods, compositions, and kits utilize a dual enzymatic process. After cytidine deaminase treatment, the DNA is first incubated with Uracil DNA Glycosylase (UDG), which generates abasic sites where dC to dU conversions have occurred. The DNA is then incubated with a high-fidelity polymerase supplemented with a deoxycytidyl transferase, such as Rev1, to repair the lesion with the installation of a cytidine.

The present invention discloses a recombinant glycosylase base editing system and its application. The recombinant glycosylase base editing system of the present invention is an APOBEC-nCas9-Ung1 or APOBEC(R33A)-nCas9-Rad51-Ung1 base editing system; the base editing system APOBEC-nCas9-Ung1 includes cytosine deaminase APOBEC, nuclease nCas9 and uracil DNA glycosylase Ung1; the base editing system APOBEC(R33A)-nCas9-Rad51-Ung1 includes cytosine deaminase APOBEC(R33A), nuclease nCas9, single-stranded DNA binding protein Rad51 and uracil DNA glycosylase Ung1. Experiments have shown that the recombinant glycosylase base editing system of the present invention can improve the editing efficiency of base C to base G in the genome sequence of an organism or a biological cell and the purity of the editing product.

The invention comprises a process for the production of a linear P-linked oligonucleotide bearing an alkyl phosphonate group at 5′-terminus of the formula Iwherein R1 is a C1-4-alkyl group, R2 is fluoro, hydroxyl or C1-4-alkoxy, X is sulfur or oxygen, the term Nucleobase stands for an optionally modified adenine, cytosine, guanine or uracil and the term oligo strand stands for the remaining P-linked oligo nucleotide strand, and wherein the oligo strand comprises at least one uracil nucleobase.The process is performed under conditions that the level of alkyl transfer impurities and the level of cyanoethyl (CNET) impurities in the linear P-linked oligonucleotide of formula I, is substantially reduced.

The invention belongs to the field of variation or genetic engineering, and discloses a T-to-G base editor for plants. The technical problem to be solved by the invention is how to realize T-to-G base editing in plants. The base editor for the plant from T to G disclosed by the invention contains a Cas protein and uracil DNA glycosylase, wherein the amino acid sequence of the uracil DNA glycosylase is 20th to 244th sites of SEQ ID No.2. The invention also discloses a preparation method of the base editor for the plant from T to G. Experiments prove that the base editor provided by the invention realizes targeted T-to-G editing with base editing efficiency as high as 78.05%, not only can solve the limitation that T direct editing cannot be realized in a rice genome, but also can induce exon jumping to obtain a required mature transcript. The base editor provided by the invention widens the targeting range of the base editor, and can also be applied to expression regulation of genes.

The invention discloses a sulfonyl-containing uracil compound and an application thereof. The structure of the compound is shown as a general formula I, wherein the definition of each substituent group in a # imgabs0 # formula is shown in the specification; also disclosed in the specification are their use as herbicides.

The invention discloses a method for detecting a genotoxic impurity 6-[[3-(2-methoxyphenylamino)propyl]amino]-1,3-dimethyluracil in an urapidil hydrochloride raw material medicine. The method has good separation, strong specificity, high sensitivity and good accuracy, and can control the genotoxic impurity 6-[[3-(2-methoxyphenylamino)propyl]amino]-1,3-dimethyluracil in the urapidil hydrochloride raw material medicine, thereby ensuring the quality of a final product and the safety of medication.

The invention discloses a saccharomyces cerevisiae recombinant strain based on a uracil metabolism gene URA3 as well as a construction method and application of the saccharomyces cerevisiae recombinant strain. The construction method comprises the following steps: taking saccharomyces cerevisiae rich in farnesyl pyrophosphate as an original strain, introducing a uracil metabolism gene URA3, synchronously overexpressing a ribosome biosynthetic gene UTP10 and an iron metabolism gene FIT3, and utilizing the uracil metabolism gene URA3 to express up-regulation correlation with the ribosome biosynthetic gene UTP10 and the iron metabolism gene FIT3, so as to obtain the farnesyl pyrophosphate-rich saccharomyces cerevisiae. The metabolic flux of the terpenoids is enhanced, and the saccharomyces cerevisiae recombinant strain for efficiently producing the terpenoids is constructed. According to the method, a metabolic network of yeast is systematically optimized, and combined regulation and control on precursor flux distribution, protein translation capability and metal ion steady state are realized, so that the microbial synthesis efficiency of sesquiterpenoids such as patchouli alcohol and beta-elemene is remarkably improved.

The invention relates to the technical field of organic synthesis, and particularly discloses a chlorinated paraffin thermal stable material as well as a preparation method and a use method thereof. The chlorinated paraffin thermal stable material is prepared from 60 to 70 parts of ethylene glycol diglycidyl ether, 15 to 20 parts of phosphite ester, 10 to 15 parts of phosphate ester, 5 to 8 parts of tetramethyltin and 3 to 6 parts of silane modified uracil. By limiting the raw material components and proportion of the chlorinated paraffin thermal stability material, the advantages of chemical structures and action principles of the raw materials are exerted, hydrogen chloride gas can be effectively captured, and further decomposition of chlorinated paraffin is prevented. According to the invention, the silane coupling agent is adopted to organically modify the uracil, so that the compatibility among the raw materials in the thermal stable material is increased, and the uniform dispersion of the uracil nitrogen-containing organic matters in the chlorinated paraffin is improved, thereby better playing the thermal stable effect and having better market application value.

The invention provides a plant cytosine single-base editor as well as a construction method and application thereof, and relates to the technical field of plant genetic engineering. The single-base editor provided by the invention is named as hyPopCBE, and has a structural formula shown in the description, the editor comprises hA3A / Y130F cytosine deaminase, an optimized human-derived Rab51 single-stranded DNA binding protein structural domain, a fusion protein of nCas9 nuclease and a uracil glycosylase inhibitor, a fusion protein expression unit of phage MS2 coat protein and the uracil glycosylase inhibitor, and a guide RNA transcription expression unit integrated with an MS2 binding sequence. Compared with an existing plant cytosine single-base editor, the single-base editor constructed by the method can remarkably improve the editing efficiency of plant alleles, and the stability is higher; when the herbicide-resistant poplar gene is applied to poplar, a new herbicide-resistant poplar germplasm can be successfully created, and a technical support is provided for research and molecular breeding of a poplar functional genome.

The present invention relates to the field of herbicides, in particular to a preparation method for a 2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-(trifluoromethyl)-3,6-dihydropyrimidin-1(2H)-yl) benzoate compound of formula (I). The present invention constructs a uracil ring under an acidic condition, and the intermediate prepared by this method can be used to prepare a novel high-efficiency uracil herbicide of structural formula (I), which has stable chemical properties and better herbicidal activity. The synthesis route is simple, and has broad application prospects in agriculture. The present invention further provides intermediate compounds used in the method, as well as methods for producing the intermediate compounds.

A phosphorothioate-containing RNA molecule that includes the nucleotide sequence: 5'-NCCCUGGUGGUCUAGUGGUUAGGAUUCGGCGC-3' (SEQ ID NO: 1), where N is uracil or thymine, is provided. The RNA molecule can include one or more phosphorothioate bonds between nucleic acid residues in one or more pairs (e.g., between nucleic acid residues in each pair) of consecutive nucleic acid residues within SEQ ID NO: 1. The RNA molecule and compositions thereof find use in treating muscle disorders, such as muscular dystrophy, heart conditions, such as heart failure or myocardial infarction, and / or conditions associated with inflammation and / or fibrosis.

The present invention belongs to the technical field of genetic engineering. Provided are a single-base editor, a deaminase used therein, and the use thereof. The technical problems to be solved are to identify a naturally occurring cytosine deaminase without sequence preference, construct a base editor, and improve the efficiency and scope of base editing. In order to solve the technical problems above, a cytosine base editor is provided. The cytosine base editor is a fusion protein, wherein the fusion protein is a protein containing a cytidine deaminase, a Cas protein and a uracil-DNA glycosylase inhibitor, and the cytidine deaminase is a protein having an amino acid sequence of positions 28-164 of SEQ ID NO. 2. Further provided is the use of the fusion protein above and a biomaterial related thereto in plant single-base editing. The single-base editor can improve the efficiency of cytosine base editing and accurately mediate the base mutation of a target, and is widely applicable in the cells of maize and even other plants.

The invention discloses a single-base editor, deaminase used by the single-base editor and application of the single-base editor, and belongs to the technical field of genetic engineering. The technical problems to be solved in the invention are as follows: natural cytosine deaminase without sequence preference is mined, a base editor is constructed, and the base editing efficiency and range are improved. In order to solve the technical problem, the application provides a cytosine base editor, the cytosine base editor is a fusion protein, the fusion protein is a protein containing cytidine deaminase, a Cas protein and a uracil glycosylase inhibitor, and the cytidine deaminase is a protein at the 28th-164th site of an amino acid sequence SEQ ID NO.2. The invention also provides application of the fusion protein and related biological materials thereof in plant single base editing. The single-base editor provided by the invention can improve the efficiency of cytosine base editing, can accurately mediate the base mutation of a target site, and can be widely applied to corn and even other plant cells.

The present invention relates to the field of pesticides, and in particular to a preparation method for a compound of formula (III). The compound of formula (III) can be used for preparing a novel highly efficient uracil herbicide. The present invention further provides an intermediate compound used in the method, a method for producing the intermediate compound, and a sterilization use of the intermediate compound. The present invention has a simple synthetic route, and wide prospects of application.

The present invention relates to a herbicide composition containing at least one of a uracil compound containing a carboxylate fragment of formula (I) or an agricultural salt thereof or a derivative thereof and at least one compound with herbicidal activity and the use thereof, wherein each variable is defined in the specification.

The invention discloses a five-membered sulfur-containing heterocyclic nucleoside lead compound and application thereof in resisting cervical cancer, pancreatic cancer and other activities, and belongs to the technical field of medicinal chemistry. A series of five-membered sulfur-containing heterocyclic ring nucleoside compounds are synthesized through a two-step Michael addition reaction, and the five-membered sulfur-containing heterocyclic ring nucleoside compounds comprise a racemate, (3S, 4R) and (3R, 4S): # imgabs0 # (* is a chiral center). Results show that in in-vitro cervical cancer (HeLa), pancreatic cancer (PANC-1) and other cell tests, the anti-tumor activity of the racemate is close to that of the enantiomer configuration. Wherein the chiral five-membered sulfur-containing heterocyclic nucleoside lead compound (3R, 4S)-15ab shows relatively strong proliferation inhibition capacity in a cervical cancer cell line, and IC50 (half maximal inhibitory concentration) reaches 2.78 mu M and is obviously superior to that of control drugs 5-fluorouracil and cis-platinum (IC50 is 9.75 mu M and 7.99 mu M respectively).

This invention discloses an ultra-low roughness chemical silver plating solution for 6G communication, comprising 2-5 g / L silver nitrate, 10-15 g / L complexing agent, 5-8 g / L nicotinic acid, 2-5 g / L reducing agent, 1-3 g / L stabilizer, 0.1-0.5 g / L surfactant, 10-30 g / L pH adjuster, 0.01-0.1 g / L grain refiner, 0.1-0.5 g / L antioxidant, and water. The invention also provides a method for its preparation. Compared with existing technologies, this invention uses specific halogenated compounds to modify uracil, improving its defects and making it less prone to ionization. The introduced groups also impart crystal plane guiding function, thereby achieving an ultra-low surface roughness of the plating layer.

The present disclosure relates to a modified 5'UTR derived from an alphavirus, such as the Venezuelan equine encephalitis virus (VEEV) wild-type 5'UTR sequence of SEQ ID NO 1 modified at least by a first nucleotide insertion, such as ribonucleotide insertion, between position 3 and position 4 of the corresponding wild-type 5'UTR sequence of SEQ ID NO 1, wherein the first nucleotide insertion is preferably guanine, adenine or uracil.

The present invention encompasses the use of general chymotrypsin inhibitors, and more specifically, substituted bicyclic substituted uracil of general formula (I) as described and defined herein, and 3-methylbenzo-[b] thiophene)-2-sulfonamido derivatives of general formula (II) for the manufacture of pharmaceutical compositions for the treatment or prevention of stroke, pulmonary embolism, pulmonary embolism, and the like. The traditional Chinese medicine composition can be used for treating thrombosis, deep vein or superficial vein thrombosis, thrombotic microangiopathy, infection, inflammation, thrombotic microangiopathy in a hypercoagulable state after transplantation, disseminated intravascular coagulation, vaccine-induced immune thrombotic thrombocytopenia, and thrombosis or occlusion at a vascular access part.

Provided are a new CRISPR-Cas12b-based base editor and the use thereof in gene expression and / or protein evolution. The base editor uses a fusion protein comprising a deaminase, a Cas protein mutant dBhCas12b and a uracil glycosylase inhibitor domain UGI, wherein the deaminase is located at the N-terminus of dBhCas12b, and comprises cytidine deaminase CDA as shown in SEQ ID NO. 1 or adenosine base editor ABE8e as shown in SEQ ID NO. 2, and the uracil glycosylase inhibitor domain UGI is located at the C-terminus of dBhCas12b, and has an amino acid sequence as shown in SEQ ID NO. 4. Compared with an original sequence as shown in SEQ ID NO. 3, dBhCas12b has mutations comprising the following: aspartic acid at position 574, glutamic acid at position 828 and aspartic acid at position 952 are mutated into alanine A.