84 results about "Cytidine" patented technology

The invention relates to a metabolic marker for diagnosing diabetic secondary osteoporosis and application of the metabolic marker, and belongs to the technical field of biological medicine. The method comprises the following steps: firstly, screening out obviously different metabolites between osteoporosis (DOP) and osteoporosis-free groups (DM) in diabetic patients; and secondly, screening out significant difference metabolites between the primary osteoporosis patient and the healthy control group, and excluding the intersection of the two groups of difference metabolites to obtain metabolites which exclude the influence of the primary osteoporosis. Metabolic markers, namely cytosine nucleotide, ketoglutaric acid and triethylamine, are obtained through further screening, and when the three metabolic markers are independently used, AUCgt; the AUC during combined use is 0.99, so that the limitation that the sensitivity of the traditional bone mineral density detection on the osteoporosis recognition in the diabetic population is insufficient is effectively made up.

The invention relates to the field of anti-tumor drugs, and discloses an anti-diffuse large B-cell lymphoma pharmaceutical composition, a preparation method and application thereof, the composition comprises azacitidine and Sanilisoma, the composition can improve the accumulation amount of VDUP1 protein in a cell nucleus through the combination of the methylation effect of DNMT3b on VDUP1 protein and the inhibition of XPO1 activity by Sanilisoma, and the anti-diffuse large B-cell lymphoma pharmaceutical composition can be used for preparing anti-diffuse large B-cell lymphoma. The chemotherapy effect is remarkably improved, the sensitivity of the DLBCL to the Sanisole is remarkably improved, and particularly, the pharmaceutical composition has a remarkable curative effect on R / R DLBCL patients.

This invention provides a simple synthesis method for Fe-Ag / CMP nanopolymers with catalase-like activity and their application in hydrogen peroxide detection, belonging to the field of bioanalytical technology. The method of this invention includes the following steps: (1) preparing a 4-hydroxyethylpiperazine thiosulfonic acid (HEPES) standard buffer solution; (2) adding cytidine monophosphate (CMP) to the solution obtained in step (1) and stirring until the CMP is fully dissolved. Then, under vigorous stirring, ferric nitrate aqueous solution and silver nitrate aqueous solution are added sequentially, at which point the colorless solution turns pale yellow; (3) transferring the mixed solution obtained in step (2) to a centrifuge tube, centrifuging at 12000 rpm for 8 min to collect the precipitate, washing it three times with distilled water, and finally adding 4 mL of distilled water to obtain a 1 mg / mL Fe-Ag / CMP suspension. This invention utilizes CMP as a biological ligand and Ag... + Fe 3+ Simultaneous coordination, and the reducing amino groups on CMP can directly transfer Ag... + In situ reduction to silver nanoparticles (AgNPs) led to the one-step synthesis of a bimetallic Fe-Ag / CMP nanopolymer with hydrogen peroxide-like nanozyme activity, enabling the detection of hydrogen peroxide.

The invention discloses a method for improving the water-resistant straw-like dwarf virus capability of rice based on D14 protein site editing and application of the method, according to the scheme, an interaction interface of RGSV P3 and rice D14 protein is analyzed through a structural biology means, and it is determined that the 102nd part, with the D14 binding site, of D14 and P3 is aspartic acid (Asp, D). Then, accurate editing of the D14 gene in the rice is realized by utilizing a cytidine base editor (CBE) system, and the site is mutated into asparagine (Asn, N), so that D14 (D102N) transgenic rice is obtained. Disease resistance identification confirms that the mutant has significant resistance to RGSV. Furthermore, a homozygous non-transgenic disease-resistant material which does not contain exogenous transgenic ingredients is obtained through genetic screening and has a good breeding application prospect.

The invention belongs to the technical field of medicine synthesis, and particularly relates to a cytidine precursor compound as well as a preparation method and application thereof. The cytidine precursor compound provided by the invention is a compound with a structure as shown in a formula (I) or a pharmaceutically acceptable salt thereof, in the formula (I), R2 is selected from one of hydrogen, formyl, acetyl, propionyl, n-butyryl and isobutyryl; r1, R3, R4, R5 and R6 are respectively and independently selected from two or three of hydrogen, hydroxyl and fluorine. The cytidine precursor compound provided by the invention is convenient to prepare oral and intravenous injection preparations, can be effectively converted into a raw drug in vivo, has bioavailability and tumor aggregation which are obviously higher than those of a cytidine raw drug, has an excellent drug treatment effect, has obvious clinical advantages, and greatly meets the clinical application requirements of cytidine antitumor drugs.

The present disclosure relates generally to pharmaceutical dosage forms comprising azacitidine and chidaridine.

The present invention relates to a method for producing α-sialyl-β-D-galactoside saccharides, particularly α-sialyl-(2→3)-β-D-galactoside saccharides and α-sialyl-(2→6)-β-D-galactoside saccharides, from a β-D-galactoside saccharide, a sialic acid donor, and an enzyme with β-galactoside α-sialyltransferase activity. The enzymes with β-galactoside α-sialyltransferase activity used herein do not exhibit catalytic activity towards the hydrolysis of cytidine 5'-monophospho-N-acetyl-neuraminic acid to cytidine and N-acetyl-neuraminic acid. The method can be performed in vitro and in vivo using a genetically engineered cell comprising a nucleic acid encoding said enzyme. Further, said process may be adapted to produce the sialic acid donor CMP-Neu5Ac from low-cost substrates N-acetyl-D-glucosamine (GlcNAc), pyruvate, a cytidine phosphate (CMP, CDP or CTP) and polyphosphate in a single reaction mixture with a set of optionally immobilized or optionally co-immobilized enzymes comprising N-acylglucoamine 2-epimerase (AGE), an N-acetylneuraminate lyase (NAL), an N-acylneuraminate cytidylyltransferase (CSS), optional a uridine kinase (UDK), a uridine monophosphate kinase and a polyphosphate kinase 3 (PPK3).

The invention discloses an application of N4-acetylcytidine (ac4C) in preparation of a medicine for delaying senescence and prolonging life. The method is realized by reducing the overall ac4C modification level of RNA (including rRNA, tRNA, mRNA, ncRNA and the like) in a living body, and specifically can be realized by inhibiting the expression of a key catalytic adapter protein THUMPD1 or using an inhibitor targeting THUMPD1 / ac4C. The invention also provides an application of a reagent for detecting the aging degree or diagnosing aging-related diseases, such as Alzheimer's disease, mitochondrial diseases, tumors and the like, in preparation of a detection kit based on the ac4C modification level of a specific target RNA molecule, and provides a brand new target spot and strategy for aging intervention and accompanying disease diagnosis and treatment.

The present invention relates to a photosensitive RNA cytidine base editor and use thereof. The photosensitive RNA cytidine base editor can cause deamination of cytidine (C) in a target double-stranded RNA to uridine (U), thereby achieving editing of C to U. The photosensitive RNA cytidine base editor comprises: (1) a dCas-eADAR2dd N-pMagHigh fusion protein, and (2) an nMagHigh-eADAR2dd C fusion protein.

The invention discloses a composite functional bacterial agent for regulating nucleoside substances in Luzhou-flavor liquor as well as a preparation method and application of the composite functional bacterial agent, and belongs to the technical field of liquor production. The compound functional bacterial agent is prepared from a liquid culture of pichia kudriavzevii GTY837 and a liquid culture of pichia kudriavzevii PKW194, or a liquid culture of pichia kudriavzevii GTY837 and a liquid culture of pichia kudriavzevii PKW194, or a liquid culture of pichia kudriavzevii PKW194, or a liquid culture of pichia kudriavzevii GTY837 and a liquid culture of pichia kudriavzevii PKW194. According to the composite functional bacterial agent provided by the invention, through the synergistic effect of the GTY837 and the PKW194, the content of seven nucleoside substances such as cytidine and hypoxanthine in the Luzhou-flavor liquor is effectively increased. The microbial agent solves the technical problem of unstable generation of nucleoside substances in traditional fermentation, and realizes synergistic improvement of the flavor and health attribute of Baijiu by enriching nucleoside substances with the functions of dispelling the effects of alcohol, protecting nerves and the like while enhancing the mellow feeling, delicate flavor and other sensory qualities of the Baijiu.

The present disclosure relates to oral dosage forms comprising an antiviral nucleoside and one or more excipients, wherein the oral dosage form is a tablet. The antiviral nucleoside is selected from a prodrug of beta-D-N (4)-hydroxycytidine (I), such as 2-methylpropionic acid {(2R, 3S, 4R, 5R)-3, 4-dihydroxy-5-[4-(hydroxyimino)-2-oxo-3, 4-dihydropyrimidin-1 (2H)-yl] oxacyclopentane-2-yl} methyl ester)-compound (A), or a pharmaceutically acceptable salt, tautomer or prodrug thereof. (I) (A)

The present application relates to a kind of cytidine choline dextrohydrotalcid derivatives and its preparation method and application, belong to biological medicine technical field.The present application is aimed at solving the technical problems of low blood-brain barrier penetration rate and limited treatment effect of existing edaravone dextrohydrotalcid compound preparation.The present application prepares a dextrohydrotalcid derivative (C-B) with boronic acid structure, then it is compounded with cytidine choline in specific pH buffer system, and forms cytidine choline dextrohydrotalcid derivative (C-D-B).The present application can effectively improve the efficiency of drug crossing blood-brain barrier by using the dynamic covalent characteristics of boronic ester bond and free radical responsiveness.The experimental results show that, compared with existing combination drug, the derivative of the present application can significantly reduce the infarction area of cerebral ischemia model animal, reduce cell damage and active oxygen level, and promote vascular regeneration, and show better treatment effect on ischemic brain injury.

The application discloses a novel cytidine derivative compound, a pharmaceutical composition of the compound and application of the compound, and the compound is shown as formula (I). The compound can be used for preparing an antiviral infection medicine.

Disclosed are a modified cytidine compound, i.e. a new derivative cytidine generated by adding a guanidyl at position 4 of a cytidine, and a nucleic acid containing the modified compound, for example, RNA. The nucleic acid containing the modified cytidine, especially mRNA, can significantly increase the expression quantity of the mRNA in vivo.

Methods of treating patients diagnosed with cancer harboring an IDH-1 mutation are provided, including the therapeutic administration of a certain inhibitor of a mutant IDH-1 as a single agent, or in combination with azacitidine (AZA).

Aspects of the disclosure relate to mRNAs comprising a relatively low abundance of cytidine: adenosine (CA) dinucleotides that benefit from increased stability relative to mRNAs containing more CpA dinucleotides. The disclosure also relates to methods of modifying an mRNA sequence to improve stability. In some aspects, the disclosure relates to mRNAs comprising modified mRNA sequences with relatively reduced numbers of CpA dinucleotides, and compositions comprising mRNAs with relatively reduced numbers of CpA dinucleotides.

The application provides a uridine monophosphate specific glycoside hydrolase and application thereof in biosynthetic synthesis of pseudouridine. Nmygdh The function of the gene is verified by in-vitro enzyme activity experiment Nmygdh The recombinant protein has broad-spectrum and high-efficiency catalytic activity, and can efficiently catalyze the hydrolysis of glycosidic bonds in various nucleotides, such as uridine monophosphate (UMP), guanosine monophosphate (GMP), adenosine monophosphate (AMP) and cytidine monophosphate (CMP), and the activity of uridine monophosphate is the strongest. The application uses the protein to efficiently hydrolyze uridine monophosphate to obtain two substrates of pseudouridine, i.e. uracil and 5'-phosphoribose, and realizes the atom-economical and efficient biosynthetic synthesis of pseudouridine by combining the cascade reaction of pseudouridine glycosidase EcPsuG and dephosphorylase EcYjjG.

The invention provides an application of acetylene cytidine in preparation of an anti-porcine epidemic diarrhea virus drug, and belongs to the technical field of chemical medicines. Experimental results show that the acetylene cytidine has remarkable inhibiting and blocking effects on a-1 ribosome framing process of the porcine epidemic diarrhea virus (PEDV), can effectively inhibit replication and proliferation of the PEDV, and has an inhibiting effect on a plurality of common strains of the PEDV; the cytidine acetylene can be used for preparing anti-PEDV medicines and medicines for preventing and treating porcine epidemic diarrhea caused by PEDV, and the medicines are wide-spectrum antiviral medicines, are insensitive to variation of PEDV and have wide application prospects.

Provided are mutant cytidine deaminases and related molecules useful for conducting base editing with reduced or no off-target mutations and with improved editing site precision. The mutant catalytic domain of the mouse APOBEC3 protein includes one or more mutations which helps to narrow the editing window while maintaining high editing efficiency. Example mutations include Y35D and K40H-W102Y. Also provided are improved base editing systems and methods using these mutant cytidine deaminases.

The invention relates to a preparation method and application of a sialylated glycan derivative, which comprises the following steps of: uniformly mixing chemically modified sialic acid monosaccharide with a receptor substrate, cytidine triphosphate (CTP), MgCl2, a CMP-sialic acid synthetase preferable mutant and sialyltransferase, transferring a sialic acid derivative to a 3-site or 6-site hydroxyl group on non-reducing end galactose of glycan by a one-pot enzymatic method, and carrying out reaction to obtain the sialylated glycan derivative. And collecting a reaction product to obtain the sialylated glycan derivative. The method is simple and can be used for editing glycans on the surfaces of the immune cells so as to enhance the specificity and cytotoxicity of the immune cells to tumor cells.

Immunomodulating polynucleotides are disclosed. The immunomodulating polynucleotides may contain 5-modified uridine, 5-modified cytidine, a total of from 6 to 16 nucleotides, and / or one or more abasic spacers and / or internucleoside phosphotriesters. Also disclosed are conjugates containing a targeting moiety and one or more immunomodulating polynucleotides. The immunomodulating polynucleotides and conjugates may further contain one or more auxiliary moieties. Also disclosed are compositions containing the immunomodulating polynucleotides or the conjugates containing one or more stereochemically enriched internucleoside phosphorothioates. Further disclosed are pharmaceutical compositions containing the immunomodulating polynucleotides or the conjugates and methods of their use.

The invention relates to a proportion-locked in-situ gel for tumor chemoimmunotherapy as well as a preparation method and application of the proportion-locked in-situ gel. The in-situ gel comprises a pharmaceutical composition and sodium alginate (ALG), wherein the pharmaceutical composition is composed of gemcitabine (GEM), oxaliplatin (OXA) and cytidine deaminase inhibitor chidauridine (CDZ), and the sodium alginate (ALG) is used as a carrier. The in-situ gel is subjected to intratumor injection and then gelation is triggered by Ca < 2 + > in a tumor, so that local retention and synchronous slow release of the medicine are realized. Metabolic inactivation of GEM is inhibited through CDZ, the optimal treatment proportion of GEM and OXA is maintained at the tumor site, and meanwhile the in-situ gel solves the problems of systemic toxicity and proportion imbalance caused by traditional intravenous administration. The synergistic effect of the pharmaceutical composition not only enhances direct cytotoxicity, but also synergistically activates anti-tumor immune response through OXA-induced immunogenic cell death and GEM-mediated regulatory T cell depletion. The invention realizes safe and efficient local chemical immunotherapy, and has a good clinical application prospect.

The present invention relates to a novel and efficient method for sialylation of a glycoside comprising mixing said glycoside with sialic acid, cytidine monophosphate, nucleoside triphosphate and one or more cell-free extracts of a microorganism, the present invention relates to a microorganism comprising one or more endogenous polypeptides having inorganic diphosphatase activity and one or more endogenous polypeptides having phosphotransferase activity, and wherein the one or more cell-free extracts comprise: at least one polypeptide having cytidine monophosphate kinase activity, at least one polypeptide having N-acyl neuraminic acid cytidyltransferase activity, and at least one polypeptide having sialyltransferase activity, thereby sialylating the glycoside.

The application discloses a kind of solid phase extraction-liquid quality connection simultaneously detecting multiple nucleotides in drinking water in the technical field of water pollution monitoring, first using solid phase extraction enrichment target material, nitrogen blow concentration, finally using the concentration of guanosine acid, adenosine acid, cytidine acid, uridine acid, deoxyguanosine acid, deoxyadenosine acid, deoxycytidine acid and deoxythymidine acid is determined using the multiple reaction monitoring mode of liquid chromatography tandem mass spectrometry, the present application combines solid phase extraction pretreatment technology with the detection technology of liquid chromatography tandem mass spectrometry, realizes the detection of trace nucleotide under complex matrix condition, the present application can realize the simultaneous determination of multiple nucleotides by one sample injection, with the advantages of high recovery rate, short detection time, many detection types and the like.

The present disclosure is concerned with modified proteins, methods, compositions, and kits for mapping of methylation status of nucleic acids, including 5-methylcytosine. In some embodiments, the proteins are altered cytidine deaminases, such as altered APOBEC3A proteins. In some embodiments, the proteins selectively act on cytosines and have significantly reduced activity on modified cytosines, such as 5-methylcytosine.

The invention discloses a method for preparing a cytidine compound. The method has the characteristics of high conversion rate, high product purity, simple production process, reasonable cost and environmental friendliness. The invention also provides a separated nucleic acid for coding the N-deoxyribose transferase, a recombinant expression vector, a transformant, an enzyme reaction system and application of the N-deoxyribose transferase or the enzyme reaction system in preparation of a compound with a general formula a as shown in the specification.

The application belongs to the technical field of analysis and detection, and provides a method for detecting residual polydimethylsiloxane content in engineering bacteria-derived cytidine 5'-diphosphocholine sodium by using ultraviolet-visible spectrophotometry. The detection method provided by the application is mainly based on the coordination reaction of polydimethylsiloxane and chromogenic solution, and uses ultraviolet-visible spectrophotometry to detect the absorbance value of the blue complex product at 621 nm. The detection method solves the problem of high cost of high-end instrument detection, and has the characteristics of high sensitivity, good repeatability and accuracy. Relevant data shows that the relative standard deviation is less than 2.0%, the recovery rate is in the range of 80% to 120%, and RSD is less than or equal to 2%.

The invention discloses truncated high-activity cytosine deaminase as well as a related biological material and application thereof, and belongs to the technical field of protein. In order to improve the base editing efficiency and range, the invention provides a 15th-150th protein with an amino acid sequence of SEQ ID NO.2 and application of the 15th-150th protein as cytidine deaminase. The invention also provides application of the protein and related biological materials thereof in single base editing. According to the application, metagenome big data is utilized, comprehensive and systematic information mining analysis is carried out on novel cytidine deaminase, and a protein L91 which is highly similar to a known DddA protein structure but low in sequence similarity is selected from the novel cytidine deaminase for functional verification. The protein L91 has high catalytic activity as cytidine deaminase, is not limited by target sequence preference, can be widely applied to gene editing in vitro and in cells / tissues, and has good application potential and development value.