42 results about "Nucleolus" patented technology

The invention discloses a preparation method and application of programmable DNA hydrogel for inhibiting breast cancer tumor activity. The DNA hydrogel is composed of an RCA long chain AL containing a multivalent AS411 aptamer sequence and an RCA long chain CL hybridized with a cholesterol single chain ss-chol. Through reasonable DNA programming sequence design, a three-dimensional DNA structure can be formed on the surface of the cell. The DNA hydrogel specifically targets cancer cells with high expression of nucleolin receptors through the synergistic effect of multivalent AS1411 and chol, and is weak in targeting to normal cells with low expression of nucleolin, so that toxic and side effects on the normal cells are effectively avoided. The DNA hydrogel has excellent programmability, hydrogel with high, medium and low pore densities can be simply prepared through flexible DNA sequence design, and the breast cancer resistance activity of the DNA hydrogel is in positive correlation with the pore density of the DNA hydrogel. In animal in-vivo experiments, the DNA hydrogel under three-dimensional and high pore density significantly inhibits breast cancer activity, and a new strategy is provided for tumor treatment.

Disclosed in the present invention are a BRIX1 inhibitor and use thereof in resisting tumors. Specifically, disclosed in the present invention is that nucleolin BRIX1 is a key regulator of the homeostasis between ribosome biogenesis and p53 activation. The research results of the present invention show that the inhibition of BRIX1 can induce nucleolar stress, leading to activation of p53, thereby inhibiting tumor growth. In addition, the present invention constructs an engineered exosome whose surface is decorated with iRGD and which is loaded with BRIX1-specific siRNA and used for cancer therapy.

The application discloses a pyridine cation mitochondrial fluorescent probe, the chemical name of the probe is 4-(8-dimethylamino-5-benzocoumarin)-methylpyridine iodine salt, and the chemical structural formula is shown as formula (I). The application further discloses application of the fluorescent probe in labeling or imaging display of mitochondrial distribution or morphology in living cells and in long-range tracking display of mitochondria in living cells and imaging display of nucleoli in cells. Experiments prove that the labeled mitochondrial fluorescent probe has high light bleaching resistance and a high fluorescence quantum yield, can realize long-range tracking of mitochondria in living cells, and can label fixed nucleoli in cells. It is indicated that the fluorescent probe has potential application and development value in the fields of fluorescent probes and tissue imaging, and has a wide application prospect.

The application provides application of nucleolin as a drug target in preparation of a double-targeted treatment drug for colorectal cancer, and application of nucleolin as a double-targeted drug target in preparation of a drug for double-targeted killing of colorectal cancer tumor cells and tumor-related fibroblasts, the drug for double-targeted killing of colorectal cancer tumor cells and tumor-related fibroblasts, a pharmaceutical composition containing the drug and application thereof. The application uses nucleolin as a common drug target of colorectal cancer tumor cells and tumor-related fibroblasts, applies a double-targeted killing drug with nucleolin as a target, simultaneously kills colorectal cancer tumor cells and tumor-related fibroblasts, removes tumor cells while destroying tumor-related fibroblast-mediated tumor supporting microenvironment, and synergistically enhances the overall treatment effect of colorectal cancer.

The application belongs to the technical field of molecular detection, and particularly relates to a method for detecting NCL conformation and G4 complex thereof based on a solid nanopore. The method is as follows: a solid nanopore is used, bias is applied on both sides of the nanopore, translocation signals of a sample to be tested through the nanopore are tested under the condition of the applied bias, and nucleolin in the sample to be tested is qualitatively and / or quantitatively analyzed through the translocation signals. By analyzing the blocking current amplitude and translocation time of NCL and G4 complex thereof entering the nanopore channel under bias, information such as the size and electrification of NCL and G4 complex thereof can be obtained. The application can detect NCL of different concentrations, greatly reduce the test cost, and at the same time, trace detection of NCL can be realized with high sensitivity and rapidness. The application provides a new research idea for targeted treatment of diseases such as cancer through detection of NCL and NCL-G4 complex.

The invention discloses an RNA (Ribonucleic Acid) fluorescent probe as well as a preparation method and application thereof in cell nucleolus staining, and belongs to the technical field of biomedical detection. The probe is a water-soluble pyridine salt compound, the chemical name of the probe is 1-(2-(2-(2, 2-dicyanovinyl))-5-(dimethylamino phenoxy) ethyl) pyridine-1-ammonium bromide, and the preparation method of the probe is characterized in that 2-(2-bromoethoxy)-4-(dimethylamino) benzaldehyde and malononitrile are used as raw materials, and the probe is synthesized through two-step reaction. The probe has the characteristics of large Stokes shift, low cytotoxicity and fluorescence enhancement after being combined with RNA (Ribonucleic Acid). Experiments prove that the probe can specifically carry out efficient fluorescence labeling on nucleolus and cytoplasm RNA in fixed cells, and a high-contrast imaging effect is obtained. The probe disclosed by the invention is simple and convenient to synthesize and excellent in performance, and has important application value in the fields of cell nucleolus research, tumor diagnosis and the like.

This invention application discloses a gene regulating maize kernel development. ZmRH51 This application focuses on the encoded proteins, functional markers, and applications of maize kernel mutants. m223 Using this as the basic material, its heterozygotes were crossed with Zheng 58 (Z58) to construct the F2 segregating population. Phenotypic identification and cytological observation were performed on the progeny segregating population. Controlling populations were obtained through genetic analysis, BSR-seq analysis, and map-based cloning. m223 Genes with mutant phenotypes ZmRH51 This gene is located in the nucleolar region and encodes an RNA helicase belonging to the DEAD-Box gene family. Studies have shown that... ZmRH51 It participates in ribosome assembly and can influence the processing of pre-rRNA in maize kernels; and further mining yields... ZmRH51 The superior allelic variant genotype of this gene in terms of grain thickness can be utilized to improve grain thickness and 100-grain weight, thereby increasing yield. Furthermore, the distribution and utilization potential of different haplotypes in inbred lines were studied, providing technical support and excellent germplasm resources for the utilization of this gene.

The application discloses a novel radionuclide therapeutic drug targeting nucleolus DDX24 helicase and a preparation method and application thereof. 64 The Cu-DOTA-TDP-2 has good tumor targeting uptake specificity, and is expected to provide a precise molecular imaging method for esophageal squamous cell carcinoma and other DDX24 high-expression malignant tumors; the novel radionuclide targeted drug 177 The Lu-DOTA-TDP-2 has high radiochemical yield and specific activity, good chemical stability, high affinity for DDX24 helicase, and a simple and easy-to-operate preparation method, and can be used for the treatment of DDX24 high-expression malignant tumors; the novel radionuclide targeted drug 177 The Lu-DOTA-TDP-2 has excellent biological safety performance and good tumor inhibition effect in esophageal squamous cell carcinoma and other DDX24 high-expression malignant tumors.

The compounds are used for the detection and imaging of amyloid plaques or both of proteins or peptides, for screening or testing the efficacy of inhibitors against amyloidosis and / or fibrillary growth of proteins or peptides, and / or for the detection of RNA and nucleolar imaging. The compounds are d 8 or d 10 Metal complexes or salts thereof. The metal complexes of said compounds can bind to amyloid proteins or peptides, plaques or both and / or RNA, nucleoli or both. This binding induces the accumulation and supramolecular self-assembly of the metal complexes, thereby causing changes in the photophysical properties of the metal complexes.

The present invention relates to the use of small artificial RNA (hereafter referred to as "smartRNA") containing sequences creating secondary structure motifs similar to C / D box small nucleolar RNAs (snoRNAs), and antisense guide sequences, as a tool for targeted upregulation of protein expression. The smartRNAs assembles into a ribonucleoprotein (RNP) complex resulting in a smartRNP, increasing the 2´-O-methylation level of one or more adenosines of the polyA-tail of the target mRNA, thereby delaying deadenylation of the targeted mRNA, resulting in increased protein production.

The present invention relates to an antiviral use of a novel peptide binding specifically to nucleolin and, more specifically, to: an antiviral composition comprising a peptide represented by a specific amino acid sequence; an antiviral composition comprising a fusion peptide in which the peptide and a cell-penetrating peptide are coupled to each other; a composition comprising the aforementioned compositions for preventing or treating a viral infection; and a health functional food composition for prevention or alleviation of a viral infection. In the present invention, a AGM peptide ligand and mutants thereof were found to inhibit viral proliferation and replication (in vitro and in vivo), as screened by an MAP synthesis method and an OBOC combination method. Therefore, NCL-targeting AGM can find advantageous applications in antiviral uses.

The present disclosure relates to compositions and methods for treating genetic disorders caused by nonsense mutations using anticodon-engineered transfer RNA (ACE-tRNA) constructs. These DNA-based ACE-tRNA constructs are designed to suppress premature termination codons (PTCs) and restore the expression of full-length, functional proteins. The disclosure further provides formulations of ACE-tRNA constructs with poly(amine-co-ester) (PACE) polymeric nanoparticles to improve stability, protect nucleic acids, and enhance delivery to airway epithelial cells. Also described are functionalized ACE-tRNA Picovectors (sLPVs) incorporating targeting elements such as nuclear localization signals (NLSs), nucleolar localization sequences (NoLSs), and DNA nuclear targeting sequences (DTSs) to improve nuclear import and localization.

The invention relates to the technical field of crossing of medical image analysis and gene detection, in particular to a construction method of a cell-level pathological feature and gene mutation data matching model, the cell-level pathological feature and gene mutation data matching model and application of the cell-level pathological feature and gene mutation data matching model. According to the method, high-resolution pathological image analysis and single-cell gene mutation sequencing technologies are combined, so that cell-level pathological feature extraction of the pathological image and accurate correlation analysis of gene mutation are realized, the accuracy and comprehensiveness of pathological diagnosis are improved, richer focus information is provided for clinicians, and the clinical application prospect is wide. The method has the advantages that a more personalized treatment scheme can be formulated, a new way is further developed for precise medical treatment of the renal cell carcinoma by comprehensively analyzing pathological characteristics such as cell morphology, nucleolus characteristics and chromatin distribution and gene mutation data, and the method has important clinical application value and social significance.

This disclosure relates to methods and compositions for treating cancer (e.g., cancers containing MSI-H cells) by: targeting WRN for degradation (in the presence or absence of a WRN inhibitor); promoting WRN association with chromatin (in the presence or absence of a WRN inhibitor); and / or promoting WRN localization from the nucleolus to foci on the chromatin.

The present application provides methods, compositions, and systems for targeted pseudouridylation of RNA. In some aspects, the present application provides methods for editing a target RNA (e.g., mRNA) in a host cell, comprising introducing an engineered guide small nucleolar RNA (gsnoRNA) into the host cell, wherein the gsnoRNA recruits a DKC1 protein to modify a target uridine residue in the target RNA to a pseudouridine residue. In some embodiments, the DKC1 protein has cytoplasmic localization in the host cell.

The application provides a near-infrared fluorescent probe and a preparation method and application thereof, and belongs to the technical field of fluorescent probes.The application takes flavones and heterocyclic compounds as asymmetric molecular building blocks, and controls the electric property, steric hindrance and water solubility of the molecular building blocks through a molecular engineering strategy to prepare the near-infrared fluorescent probe.The near-infrared fluorescent probe has the advantages of long fluorescent emission wavelength, large stokes shift and the like, and effectively avoids the interference of biological background fluorescence.In the aspect of nucleic acid labeling, the near-infrared fluorescent probe has the significant advantages of high signal-to-noise ratio, good selectivity and good biocompatibility.The near-infrared fluorescent probe is imaged by using a laser confocal microscope and a structured illumination super-resolution fluorescence microscope, and the RNA in HeLa cells and mouse white blood cells is successfully traced and displayed, and the fine structure of nucleoli can be visualized at a high resolution.

The invention discloses a DNA (Deoxyribose Nucleic Acid) aptamer for targeting nucleolin and application of the DNA aptamer, belongs to the technical field of oligonucleotides, and particularly relates to the DNA aptamer for targeting nucleolin. The DNA nucleic acid aptamer is obtained by reacting AS1411 of which the 5'end is modified by amino and a triptolide derivative; the triptolide derivative is obtained by modifying triptolide with a vinyl carboxylic acid derivative; the vinyl carboxylic acid derivative is prepared by the following preparation steps: under the action of a catalyst, allyl succinic anhydride firstly reacts with 4-(chloromethyl) benzyl alcohol, and then reacts with sodium bicarbonate to obtain the vinyl carboxylic acid derivative. The DNA aptamer for targeting nucleolin disclosed by the invention not only can be efficiently combined with nucleolin, but also has good effects of inhibiting tumor cell proliferation and inhibiting tumor growth.

The invention discloses a near-infrared RNA fluorescent probe, a preparation method of the near-infrared RNA fluorescent probe and application of the near-infrared RNA fluorescent probe in super-resolution imaging dynamic analysis of nucleolus RNA, and belongs to the technical field of fluorescent probes. The probe is a quinoline-benzothiazole salt derivative, and has the advantages of near-infrared emission, large Stokes shift, high RNA binding affinity and excellent light stability. The molecular marker can quickly penetrate through a cell membrane, specifically marks nucleolus RNA and is hardly interfered by DNA (Deoxyribose Nucleic Acid). And in combination with a structured light illumination microscope, ultra-clear imaging with the resolution of about 100 nm can be realized, and substructures such as a fiber center and a compact fiber component in a nucleolus can be accurately analyzed. Compared with SYTO RNA Select, the probe has the advantages that the combination is stronger, the light stability is better, the probe is successfully applied to real-time monitoring of dynamic changes of nucleolus RNA in the ferroptosis process, the evolution rule of nucleolus morphology and RNA expression in a fatty liver disease model is disclosed, and an efficient tool is provided for research of related mechanisms of nucleolus.

Methods and compositions useful for delivering a protein to a plurality of nuclei in a cell. Fusion proteins comprising one or more signals useful for promoting delivery of the proteins to a plurality of nuclei in a multinucleate cell. Methods comprising administering isolated nucleic acids to a multinucleate cell, wherein the isolated nucleic acid comprises a sequence encoding a fusion protein, the fusion protein comprising, a protein of interest fused to at least the following migration signals: (a) at least one nuclear export signal (NFS); and (b) at least one nuclear localization signal (NLS) and / or at least one nucleolar localization signal (NoLS). Fusion proteins comprising: (a) a protein of interest; and (b) at least the following migration signals: (i) a nuclear export signal (NFS); (ii) a nuclear localization signal (NLS); and (iii) a nucleolar localization signal (NoLS). Methods of making and using the same. Methods of delivering recombinant genes and / or fusion proteins to multinucleate cells.

The application discloses an AIE fluorescent dye, a structural formula of which is shown in the following formula (I), wherein R1 and R2 are independently selected from alkyl alcohol with carbon number of 1-6; and X is selected from water-soluble anions. The fluorescent dye disclosed by the application has AIE characteristics, can realize rapid staining of living cells, and the staining depth can be deep to the nucleolus of the cell nucleus, so that the morphology of the whole cell tissue is clear and visible; is expected to be applied in the field of living cell fluorescence imaging, and further used for preparing a fluorescent kit for rapid diagnosis of cancer cells; the fluorescent probe has good water solubility, small cytotoxicity and good biocompatibility; the fluorescent color is orange red, the Stokes shift is large, and the anti-self-fluorescence interference ability is strong.

The application discloses a nucleolus-targeted carbon dot and a large-scale preparation method and application thereof, and relates to the technical field of nanometer materials. The large-scale preparation method of the nucleolus-targeted carbon dot is as follows: selecting m-phenylenediamine as a precursor, sulfuric acid as an oxidant and a dehydrating agent, and adopting a solid-phase calcination method to prepare the carbon dot; and the prepared carbon dot is subjected to suction filtration, washing and drying to obtain the nucleolus-targeted carbon dot. The carbon dot prepared by the application has intrinsic nucleolus-targeting property, excellent fluorescence performance and high biocompatibility, and is suitable for nucleolus-targeted fluorescence imaging. The preparation method of the application only adopts a suction filtration and washing mode to realize purification treatment, and the sample can be obtained without dialysis, so that the experimental period is shortened, and large-scale production of hundreds of grams can be realized.

The invention belongs to the field of anticancer active natural components, and particularly relates to anticancer active glycoprotein, a preparation method and application of the anticancer active glycoprotein and an anti-female cancer medicine, and the anticancer active glycoprotein is protein chemically bonded with selenium and polysaccharide. The protein comprises a peroxidase structural domain protein, RNA dependent RNA polymerase, a nucleolus 278 pre-rRNA processed Urb / Npa2 C-terminal structural domain protein and a ribosomal protein S12; the polysaccharide chain is a sugar unit fragment with a structure shown in a formula 1; hydroxyl in the polysaccharide is connected with at least one amino acid of aspartic acid, valine, glutamic acid, arginine, lysine and serine in the protein through a hydrogen bond; the selenium bond comprises at least one of Se = O and Se-C-O. The invention provides a selenoglycoprotein component with a brand new structure, and further research shows that the selenoglycoprotein component can specifically inhibit female cancer cells and has relatively low normal cell inhibitory activity.

The invention provides a construction method of a mouse heart failure model based on NCL gene myocardial specific knockout induction and application of NCL gene myocardial knockout. According to the method, Nclflox / flox and Myh6-Cre mice of 5-6 weeks old are used, NCL genes in cardiac muscle cells of the mice are specifically knocked out, the mice are continuously fed until the ejection fraction of a left ventricle is smaller than 50%, and the adult mouse heart failure model based on cardiac muscle cell nucleolin specific knockout is obtained. The successful construction of the model provides a key technical support for exploring heart diseases mediated by nucleolin-related pathways in myocardial cells, effectively fills the blank of demands of the research field in the aspect of experimental vectors, and has indispensable important significance for promoting heart disease mechanism research and transforming medical development.

The present application relates to the fields of biotechnology and RNA editing. The invention relates to an RNA single base editing system and method based on pseudouridine modification. In particular, the present application relates to a method for inhibiting an early termination codon (PTC) in a target RNA in a host cell. The present application also relates to an engineered guide small nucleolus RNA (gsnoRNA), an isolated nucleic acid molecule comprising the same, a composition, and a host cell. The present application also relates to their use in the preparation of medicaments. According to the method provided by the invention, the efficiency of pseudouridine modification can be remarkably improved, so that the coding information of mRNA is recovered, the PTC site is decoded, and the read-through efficiency of PTC is remarkably improved.

The invention discloses application of a substance aiming at a VDAC1 target spot in preparation of a product and a medicine for preventing and treating diseases caused by RSV, and relates to the technical field of respiratory syncytial virus resistance. A novel RSV cell receptor VDAC1 (voltage-dependent anion channel 1) independent of NCL (nucleolin) is discovered, a novel RSV infected cell receptor is identified, and discovery of the receptor provides a molecular basis for development of novel antiviral drugs and is crucial for development of novel drugs. The substance aiming at the VDAC1 target spot, provided by the invention, has a good application prospect in prevention and treatment of diseases caused by RSV, and the resistance of a subject to RSV infection can be greatly improved.

The present application relates to the field of biotechnology and the field of RNA editing. The present application relates to a RNA single base editing system and method based on pseudouridine modification. Specifically, the present application relates to a method for inhibiting a premature termination codon (PTC) in a target RNA in a host cell. The present application also relates to an engineered guide small nucleolar RNA (gsnoRNA), an isolated nucleic acid molecule comprising the same, a composition, a host cell. The present application also relates to the use thereof in the preparation of a medicinal product. The method of the present application can significantly improve the efficiency of pseudouridine modification, thereby restoring the coding information of mRNA, making the PTC site be decoded, and significantly improving the efficiency of PTC readthrough.

The invention relates to the technical field of biochemical sensing and fluorescence imaging, in particular to a chromazole near-infrared viscosity-sensitive probe, a preparation method thereof and application of the probe in living cell imaging. The preparation method of the probe comprises the following steps: dissolving tryptazole tetrafluoroborate and benzaldehyde or a derivative thereof in acetonitrile, stirring at room temperature to react, evaporating to remove a solvent after the reaction is finished, and separating and purifying through column chromatography to obtain the tryptazole near-infrared viscosity sensitive probe. The application of the probe in living cell nucleus imaging is to mark chromosomes in a cell mitosis process, so that chromosome migration behaviors are visualized. The probe is high in utilization rate, mild in preparation reaction condition, simple and convenient to operate, green and efficient. The cell nucleus of the living cell can be quickly dyed at low concentration, the cytoplasm, the nuclear membrane and the nucleolus of the living cell can be distinguished through the fluorescence brightness, and the mitosis process of the cell can be traced. A feasible strategy is provided for developing a near-infrared probe with a rapid cell nucleus staining function.

The present application relates to the technical field of medical image analysis and gene detection, in particular to a cell-level pathological feature and gene mutation data matching model construction method, a cell-level pathological feature and gene mutation data matching model and application thereof. The present application realizes cell-level pathological feature extraction of pathological images and precise correlation analysis of gene mutations by combining high-resolution pathological image analysis and single-cell gene mutation sequencing technology. This innovation not only improves the accuracy and comprehensiveness of pathological diagnosis, but also provides more rich lesion information for clinicians, which helps to develop more personalized treatment plans. Through comprehensive analysis of pathological features such as cell morphology, nucleolus features and chromatin distribution and gene mutation data, a new way for precise medical treatment of renal cell carcinoma is further opened up, which has important clinical application value and social significance.

The application belongs to the field of anticancer active natural ingredients, and particularly relates to an anticancer active glycoprotein, a preparation method and application thereof, and an anticancer drug for female cancer, wherein the anticancer active glycoprotein is a protein chemically bonded with selenium and polysaccharide, the protein includes a peroxidase domain protein, an RNA-dependent RNA polymerase, a nucleolar 278 pre-rRNA processing Urb / Npa2 C-terminal domain-containing protein, and a ribosomal protein S12; the polysaccharide chain is a sugar unit fragment with a structure of formula 1; the hydroxyl in the polysaccharide is connected to at least one amino acid in aspartic acid, valine, glutamic acid, arginine, lysine and serine in the protein through a hydrogen bond; and the selenium bond includes at least one of Se=O and Se-C-O. The application provides a novel structure of selenium glycoprotein ingredient, and further research shows that the ingredient can specifically inhibit female cancer cells and has a lower normal cell inhibition activity.

The present disclosure relates to compositions and methods for treating genetic disorders caused by nonsense mutations using anticodon-engineered transfer RNA (ACE-tRNA) constructs. These DNA-based ACE-tRNA constructs are designed to suppress premature termination codons (PTCs) and restore the expression of full-length, functional proteins. The disclosure further provides formulations of ACE-tRNA constructs with poly(amine-co-ester) (PACE) polymeric nanoparticles to improve stability, protect nucleic acids, and enhance delivery to airway epithelial cells. Also described are functionalized ACE-tRNA Picovectors (sLPVs) incorporating targeting elements such as nuclear localization signals (NLSs), nucleolar localization sequences (NoLSs), and DNA nuclear targeting sequences (DTSs) to improve nuclear import and localization.