65 results about "Nucleolus" patented technology

The present disclosure provides compositions and methods of use thereof for targeting trans- splicing of a pre-mRNA in a cell utilizing small nuclear RNAs (snRNAs) and small nucleolar RNAs (snoRNAs), and related methods.

The invention discloses an application of a soybean nucleolus GTP binding protein gene GmNSN1 in soybean resistance to soybean mosaic virus diseases. The invention relates to an application of a soybean nucleolus GTP binding protein gene GmNSN1 as shown in SEQ ID NO.1 and SEQ ID NO.2 in genetic engineering modification of soybean mosaic virus resistance. The soybean nucleolus GTP binding protein gene GmNSN1 can negatively regulate and control the resistance of soybeans to diseased soybean mosaic virus diseases, and the antiviral response of the soybeans can be activated due to function deficiency of the soybean nucleolus GTP binding protein gene GmNSN1. The gene is knocked out through a CRISPR / Cas9 gene editing technology, so that the resistance of soybeans to the soybean mosaic virus disease can be remarkably improved.

The invention belongs to the technical field of plant gene engineering, and particularly relates to an OsNUC1 gene and application of a gene mutant constructed by the OsNUC1 gene to regulation and control of rice plant height, leaf length and panicle type. The regulation is to regulate the plant height and leaf growth of the rice and influence the shape of the ear part. Compared with the prior art, the OsNUC1 gene mutant has the following advantages: (1) the OsNUC1 is directionally edited by utilizing a CRISPR / Cas9 gene editing technology, an OsNUC1 gene mutant rice material is obtained, the biological phenotype of the OsNUC1 gene mutant rice material is investigated, the phenotype investigation on T1-generation seedlings of the OsNUC1 shows that the plant heights and the leaf lengths of one-week-old and two-week-old seedlings of the mutant are obviously higher than those of wild seedlings, the leaf widths have no obvious difference, and the OsNUC1 gene mutant rice material has a good application prospect; the result shows that the OsNUC1 can regulate the plant height and the leaf growth of the rice and influence the shape of the ear part. (2) it is proved that the nucleolin gene OsNUC1 is negatively regulated by a transcription factor OsARF7, and the phenotypes such as the plant height, the leaf length, the grain length and the grain width of the OsNUC1 / OsARF7 mutant are more obvious than those of the OsNUC1 mutant. The invention further proves the application of the OsNUC1 gene in regulation and control of rice plant height and leaf growth.

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 present invention relates to a novel peptide that specifically binds to nucleolin, and more specifically, to a peptide expressed by a specific amino acid sequence, a conjugate comprising the peptide and an anticancer drug, a fusion peptide comprising the peptide and a cell-penetrating peptide, a composition comprising the peptide for diagnosing cancer, and a composition comprising the peptide or the conjugate for preventing or treating cancer. In the present invention, the peptide ligand AGM peptide and its mutants, screened using the MAP synthesis method and the OBOC combination method, have been shown to specifically bind to cancer cells, and their conjugates with anticancer drugs inhibit cancer growth (in vitro and in vivo). Therefore, the AGM peptide targeting nucleolin can be effectively used for diagnosis and targeted drug delivery in cancer treatment.

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.

Provided in the present invention are a cytopathological staining kit and a staining method. The staining kit comprises a basic fuchsin staining reagent, a silver nitrate staining reagent, an ethanol-hydrochloric acid fixation solution, a gelatin-formic acid reducing solution, and a washing solution. The kit can reveal the complete cellular structure and morphology thereof, and can particularly delineate the morphology of a nucleolus of a cell nucleus.

Provided herein are antibodies specific for nucleophosmin 1 (NPM1), which are capable of binding to nucleophosmin 1 located on the surface of cells, as well as antibody-drug conjugates (ADCs) comprising such antibodies. Also provided herein are methods of treating cancers in which NPM1 is expressed on the surface of cancer cells, by administering to a subject an NPM1-binding antibody or antibody conjugate described herein and a chemotherapeutic drug.

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 invention discloses an application of a substance for reducing the activity and / or expression quantity of RPL22 protein in delaying senescence. Experiments prove that the senescence phenotype of cells can be delayed by deletion of the RPL22 protein, the senescence phenotype of the cells can be accelerated by overexpression of the RPL22 protein, in addition, in the senescence occurrence process or under the condition of overexpression of the RPL22 protein, the senescence phenotype of the cells can be accelerated by inducing reduction of the levels of HP1gamma, KAP1 and H3K9me3 heterochromatin proteins on a heterochromatin region on nucleolus rDNA, so that the senescence phenotype of the cells can be delayed, and the senescence phenotype of the cells can be accelerated. Then heterochromatin is induced to be depolymerized, the transcription level of rDNA is increased, rRNA expression is increased, and the nucleolus structure is affected. The deficiency of RPL22 can relieve the occurrence of the phenotypes. Therefore, the RPL22 can be used as a potential target for preventing, relieving or treating aging or aging-related diseases. The method has an important application value.

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 invention provides a chromosome N-G banding method, which comprises the following steps: S1, preparing a slide: preparing a split phase glass slide with better quality; s2, adding the solution, sucking two drops of the solution A and four drops of the solution B, dripping into a test tube, quickly mixing, and dripping on a glass slide to be dyed; s3, dyeing, covering with cover glass, and heating the cover glass on a sheet baking plate preheated to 70 DEG C; the dye liquor becomes yellow within 30 seconds of heating and becomes deep golden brown within 2 minutes; s4, washing the slide, uncovering the cover glass, washing the slide with flowing distilled water, then throwing off water drops, and baking the slide at 65 DEG C for 30 minutes; S5, banding, Giemsa banding and dyeing, namely preparing six dye vats, dip-dyeing for multiple times according to a set sequence, drying and then developing, dyeing a nucleolus area into black, and dyeing chromosomes into purple. According to the method, the variation of the NOR region and the chromosome stripe can be observed at the same time, so that the accuracy of judging the variation of the NOR region is improved.

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 invention belongs to the technical field of biological medicines, and relates to application of small nucleolus SnoRD89 in preparation of an ovarian cancer targeting drug. The invention discloses that SnoRD89 inhibits the malignant phenotype of ovarian cancer cells by influencing the RPL11 / MDM2 / P53 pathway for the first time. The invention finds a new effective method for targeted regulation and control of apoptosis signal channels, that is, ovarian cancer cell apoptosis is induced through siRNA of targeted SnoRD89, and the method is applied to basic medical research.

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.

Provided herein are antibodies specific for nucleophosmin 1 (NPM1), which are capable of binding to wild-type and / or mutant nucleophosmin 1 located on the surface of cells. These antibodies, as well as antibody conjugates comprising these antibodies, are useful for the detection and treatment of cancers in which NPM1 is expressed on the surface of cancer cells.

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.

The present invention provides a use for a small nucleolar RNA (snoRNA) or a detection reagent thereof, for use in detection of a servitization state of cells; moreover, detection and regulating methods for the snoRNA are established.

The invention relates to the field of cell classification, in particular to a cell classification and function evaluation method and system based on deep learning nucleolus morphology. The method provided by the invention comprises the following steps: S101, acquiring microscopic image data of a biological sample; s102, acquiring a first region of interest, a second region of interest and a third region of interest; s103, extracting kernel feature data; s104, carrying out first classification on cells in the biological sample; and S105, calculating the number and / or proportion of the A-type cells and the B-type cells in the biological sample so as to evaluate the functional state of the tissues or organs corresponding to the biological sample. The method can accurately and sensitively reflect and evaluate the functional state of the tissue or organ corresponding to the biological sample, and is especially suitable for the biological sample which is lack of a specific marker and has strong heterogeneity.