130 results about "Targeted Modification" patented technology

The invention provides a method for genetically modifying bordetella pertussis and application of the method. The method comprises the following steps: knocking down or knocking out a first nutrition screening gene of bordetella pertussis to generate a first auxotrophic cell; replacing the first genetic element with a second nutrition screening gene through recombination treatment to obtain a second auxotroph cell; replacing the second nutritional screening gene with the genetically modified second genetic element through recombination treatment to obtain a third nutritional deficient cell; and restoring the first nutritional screening gene to the genome of the third nutritional deficient cell through recombination treatment. In the modification process, use of antibiotics is not involved, no redundant fragments are introduced except for target modification sites, and the method has the advantages that the genetic background purity is high, and no biological safety risk exists in the modification process.

The present disclosure provides compositions and methods for the targeted modification of RNA molecules by RNA prime editing. The compositions and methods may be conducted invitro or in vivo within cells (e.g., human cells) for the therapeutic correction of disease-causing mutations and / or installation of motifs or mutations in RNA molecules of interest as a tool for scientific research. The disclosure provides compositions and methods for conducting RNA prime editing of a target RNA molecule (e.g., an RNA transcript) that enables the incorporation of one or more nucleotide changes and / or targeted mutagenesis of a target RNA molecule. The nucleotide change can include a single-nucleotide change, an insertion of one or more nucleotides, or a deletion of one or more nucleotides. More in particular, the disclosure provides a variety of configurations of the RNA prime editors each comprising a nucleic acid programmable RNA binding proteins (napRNAbp), such as Cas13, and an RNA-dependent RNA polymerase (RDRP), which are provided as fusion proteins or which can be separately provided in trans. The RNA prime editors are guided to a target RNA site by a guide RNA, which can be a rpegRNA that includes a template region for the synthesis of an RNA sequence to be installed on the RNA molecule attached to an available 3′ terminus. In others embodiments, the RNA template can be provided in trans.

The invention belongs to the technical field of plant genetic engineering, and particularly relates to application of a wheat transcription factor TaWRKY22 and a coding gene thereof in regulation and control of plant stripe rust resistance. The function of the wheat transcription factor TaWRKY22 is researched through molecular biology and genetics methods, it is found that knockout of the TaWRKY22 gene significantly improves the resistance of wheat to stripe rust, overexpression of the TaWRKY22 gene reduces the resistance of wheat to stripe rust, and then it is indicated that the wheat transcription factor TaWRKY22 plays a negative regulation role in wheat stripe rust resistance. Therefore, the TaWRKY22 gene is subjected to targeted modification through a gene editing technology, a new genetic material and a molecular breeding strategy can be provided for wheat stripe rust resistance breeding, and an important material and technical support are provided for breeding of wheat disease-resistant varieties.

The invention provides a modification processing method and processing system based on beam shaping, and the method comprises the following steps: obtaining three-dimensional light field distribution corresponding to a three-dimensional model through a holographic algorithm according to the three-dimensional model of a target modification structure, and generating a phase modulation diagram; loading the phase modulation diagram through a spatial light modulator, and modulating the wavefront phase of the incident laser, so that a light beam is focused on the surface of the material or in the material to form a preset spatial curved surface light field; and the spatial curved surface light field is focused on the material, so that the material in the light field region is subjected to nonlinear absorption or phase change, and a modified structure of a three-dimensional model is directly formed. According to the method, the limitation of traditional point-by-point scanning type machining is broken through, the machining efficiency and flexibility of a complex three-dimensional structure are remarkably improved, the method is suitable for scenes such as transparent material internal waveguide inscribing, curved surface splinter separation, large-area stripping, functionalized surface preparation and opaque material huge removal machining, and the machining efficiency and quality are remarkably improved.

The embodiment of the invention provides a code task processing method, a code error correction method and a code processing model training method. The code task processing method comprises the steps of obtaining an original code file and an original modification scheme of the original code file; adding a region identifier in the original code file and the original modification scheme to obtain a to-be-processed code file and a to-be-processed modification scheme; inputting the to-be-processed code file and the to-be-processed modification scheme into a code processing model to obtain a region identifier sequence; and generating a target modification file of the original code file according to the region identifier sequence. By introducing the region identifiers, the mode of generating codes by the model is switched into the mode of only generating the region identifiers, the length of a model output text is greatly reduced, the generation speed is increased, and due to the fact that all the region identifiers are associated with an original code file and an original modification scheme, the generation efficiency is greatly improved. The target modification file can be quickly generated based on the region identifier sequence, and the generation efficiency of the target modification file is improved.

The invention relates to an RGD (arginine-glycine-aspartic acid) peptide modified mercaptododeborane derivative and a synthesis method, the derivative utilizes RGD peptide to perform chemical coupling modification on mercaptododeborane anion salt (BSH), and the BSH and the RGD peptide are connected through a hydrophilic intermediate connector with a double bond at one end and carboxyl at the other end. A hydrophilic chain is selectively introduced to serve as an intermediate connector, a series of compounds are synthesized through a convenient and efficient sulfydryl-alkene click reaction and an amino-carboxyl amidation condensation reaction and are purified, various cationic BSH salts and RGD peptide are connected, and targeted modification of the RGD peptide on an existing boron carrying agent BSH is achieved. The derivative obtained by the invention is not reported before, has the potential to improve the tumor targeting ability of the existing boron carrying agent, and is expected to be used as a drug compound for BNCT treatment.

The invention relates to the technical field of biomedical engineering and drug delivery, and particularly discloses a novel targeted drug delivery system based on rose fruit extracellular vesicles, which comprises the following steps: preparing rose fruit source extracellular vesicles; preparing a medicine carrying vesicle; preparing targeted modified drug-loaded vesicles; according to the application disclosed by the invention, a stem related pathway is specifically down-regulated through the components of the rose fruits, and meanwhile, conventional tumor cells are killed by using adriamycin, so that a complementary treatment mechanism is formed, and the tumor recurrence risk is fundamentally reduced. The phenylboronic acid group of DSPE-PEG-PBA is used for specifically recognizing sialic acid over-expressed on the surface of a tumor cell, so that the enrichment of the medicine in tumor tissues is remarkably improved, and meanwhile, the distribution of normal tissues is reduced. By means of the natural biocompatibility and low immunogenicity of the RHNVs and in combination with the long circulation characteristic of a PEG chain, the delivery efficiency is guaranteed, the systemic toxicity is reduced to the maximum extent, and particularly the cardiotoxicity and myelosuppression of adriamycin are relieved.

The invention discloses a copywriting modification method and device, a terminal and a storage medium, and relates to the technical field of artificial intelligence. The method comprises the steps of generating a second evaluation standard for an initial copywriting and a first evaluation standard through a copywriting evaluation model; evaluating the initial copywriting according to the second evaluation standard to obtain a target evaluation opinion; and generating a target modification opinion based on the target evaluation opinion. According to the document evaluation model, the initial first evaluation standard is supplemented and perfected, and a more comprehensive second evaluation standard is generated. The initial copywriting is evaluated based on the second evaluation standard, accurate target evaluation opinions can be output to clarify specific problems existing in the copywriting, targeted target modification opinions are generated according to the target evaluation opinions, and automatic modification of the copywriting can be achieved. The problems that the manual modification level is difficult to keep consistent and the cost is high are solved.

The application discloses a method for producing deoxythymidine triphosphate by using a recombinant strain, and comprises the following steps: step 1: using a CRISPR / Cas9-mediated gene editing method to perform targeted modification on an E. coli genome, and the targeted modification comprises the following contents: a. knocking out a nucleoside triphosphate pyrophosphatase gene (mazG / yhdE) to block a path of degrading dTTP into dTMP; b. knocking out a nucleotide nucleosidase gene (ppnN) to block a path of degrading dTMP into thymine; and c. knocking out a nucleotidase gene (yfbR / yfdR / ushA / umpH / umpG / yjjG) to block a path of degrading dTMP into dT. The application provides a method for producing deoxythymidine triphosphate by using a recombinant strain, and the conversion rate of the method reaches 80% to 90%, and after ion exchange chromatography purification, the purity can reach more than 99%.

This invention relates to the field of metal material strengthening technology, specifically a method and system for enhancing the wear resistance of gate valves based on surface modification. The method includes: receiving a gate valve strengthening command; determining a target gate valve based on the command; identifying a set of target modification regions based on the target gate valve; performing surface pretreatment on multiple target modification regions within the target modification region set to obtain multiple pretreated modification regions; setting multiple powder mass ratios; constructing multiple laser cladding parameters; obtaining multiple cladding samples based on the laser cladding parameters and powder mass ratios; performing cladding performance testing on the multiple cladding samples to obtain multiple performance scores; determining a target cladding parameter combination based on the performance scores; and performing laser cladding on the multiple pretreated modification regions using the target cladding parameter combination to obtain a wear-resistant strengthened gate valve. This invention can improve the wear resistance of gate valves and extend their service life.

A duchenne muscular dystrophy-related exonic splicing enhancer, sgRNA and gene editing tool can be applied in the preparation of drugs for treating duchenne muscular dystrophy. The gene editing tool designed on the basis of cytosine deaminase AID mutants and Cas9 mutants can perform site-specific modification on a mammalian genome by using an adeno-associated virus (AAV) as a vector. By optimizing an encoding nucleic acid sequence and an element composition structure of the editing tool, site-specific targeted modification of mammalian genetic material DNA can be efficiently achieved; and by performing targeted genetic manipulation on the nucleic acid sequence carrying disease mutations, a pathogenic mutation cannot be retained in a mature protein amino acid sequence or the pathogenic mutation cannot perform its function, so that the purpose of treating various gene mutation type genetic rare diseases is achieved, and the advantages of high efficiency, safety and stability are achieved.

The invention relates to the field of computer data processing, and discloses a data integration method, device and equipment, and the method comprises the steps: generating equipment identification information corresponding to a plurality of pieces of computer equipment associated with a target user, and building an equipment information list; and if the equipment information of the current computer equipment is matched with the equipment information list, calling real-time modification data of the current computer equipment, carrying out modification action identification on the real-time modification data, obtaining target modification data corresponding to the target user, and carrying out data integration and updating on cloud storage data of the target user. According to the data integration method, device and equipment of the computer equipment, the computer equipment and the operation user generating modified data are synchronously recognized in the data integration process, the pertinence and integration efficiency of the data are effectively improved, and meanwhile, the user can conveniently, rapidly and accurately inquire the needed data.

The embodiment of the invention provides a data processing method and device, equipment, a storage medium and a program product. The method comprises the following steps: acquiring a filled change description template; wherein the filled change description template comprises change content; the change content comprises table structure change information and data content change information; determining a data link relationship according to the filled modification description template; wherein the data link relationship represents a data influence range of the change content on the data in the data; determining a target modification path based on the data link relationship; and processing the corresponding data in the data table based on the target modification path and the filled modification description template. According to the embodiment of the invention, the change content filled by using the uniform change description template is combined with the target change path, so that the corresponding data in the data-in-the-channel can be automatically processed, and meanwhile, the change of the data in the data-in-the-channel can be reduced, and the maintenance cost of the change of the data in the data-in-the-channel can be reduced.

The invention belongs to the technical field of biological materials, and particularly relates to a pathogen-targeted engineered exosome as well as a preparation method and application thereof. The engineered exosome provided by the invention comprises an adipose-derived stromal cell exosome, antibacterial peptide M27-39 and 6 '-sialic acid lactose, and integrates two functions of resisting influenza virus and relieving viral pneumonia, targeted modification of 6'-SL can simulate a host receptor structure, and binding of HA and sialic acid is competitively blocked. After the antibacterial peptide M27-39 carried by the exosome is released in the lung, the direct antiviral effect can be achieved, excessive inflammatory response induced by viruses is inhibited, and meanwhile lung injury caused by influenza virus infection is relieved by promoting alveolar epithelial cell repair and relieving pathological injury of viral pneumonia. Therefore, the engineered exosome provided by the invention can be combined with pathogenic microorganisms in a targeted manner, and has obvious functions of resisting pathogenic microorganisms, resisting inflammation, repairing barriers and intervening the pathological process of infectious lung injury.

The embodiments of this specification provide a method for code task processing, code error correction, and code processing model training, wherein the code task processing method includes: obtaining an original code file and an original modification plan of the original code file; adding a region identifier to the original code file and the original modification plan to obtain a code file to be processed and a modification plan to be processed; inputting the code file to be processed and the modification plan to be processed into a code processing model to obtain a region identifier sequence; and generating a target modification file of the original code file according to the region identifier sequence. By introducing the region identifier, the mode of model code generation is switched to a mode of generating only the region identifier, which greatly reduces the length of the model output text and speeds up the generation speed. Since each region identifier is associated with the original code file and the original modification plan, the target modification file can be quickly generated based on the region identifier sequence, thereby improving the generation efficiency of the target modification file.

The invention discloses a carbonyl reductase directional modification method for synthesis of atorvastatin intermediates, which belongs to the technical field of enzyme gene engineering, and is characterized in that carbonyl reductase genes are used as templates, mutation primer pairs are designed, double-site mutation is carried out by adopting an overlapping extension PCR (polymerase chain reaction) method, escherichia coli is transformed, IPTG (isopropyl-beta-d-thiogalactoside) is used for inducing expression, and mutant carbonyl reductase is prepared. The K205D / R237W double mutation modified carbonyl reductase improves the enzyme activity, combines the synergistic effect of the thiophene pyridine coenzyme analogue, improves the conversion rate of the atorvastatin intermediate and the product purity, is significantly superior to the traditional chemical reduction method, avoids the low-temperature and high-pressure conditions of the traditional chemical method, reduces the energy consumption, and is suitable for industrial production. The use amount of an organic solvent and the generation amount of byproducts are reduced, and the generation amount of wastewater is reduced.

The invention discloses application of a thermal induction type RCA1 gene in improving heat resistance of plants. The nucleotide sequence of the thermal induction type RCA1 gene is shown as SEQ ID NO. 1. The RCA1 gene disclosed by the invention has the function of maintaining the photosynthesis efficiency of plants under high-temperature stress, enriches the heat-resistant molecular theory of the azalea, and has important practical significance in improving the heat-sensitive defect of the azalea, improving the cultivation efficiency and improving the adaptability and attractiveness of the azalea in landscape architecture. In addition, the application of the RCA1 gene is not limited to rhododendron, can also be used for heat resistance improvement of other plants, and is of great significance to plant heat resistance oriented transformation.

The present invention discloses a method for delivering siMMP13 to chondrocytes by targeting peptide-modified Expi293 cell exosomes, comprising the following steps: separating and purifying Expi293 cell exosomes, labeling Expi293 cell exosomes, coupling DSPE-CAP polypeptide with Expi293 cell exosomes in a targeted manner, and then loading siMMP13 into the targeted modified Expi293 cell exosomes by electroporation. The present invention targets and modifies Expi293 cell exosomes to deliver siMMP13 through a chemical modification scheme, has a simple preparation method, high targeting, good aggregation effect at damaged parts, and realizes efficient drug release. Targeted delivery of siMMP13 can inhibit the metabolic decomposition of cartilage matrix, thereby inhibiting the progression of osteoarthritis, and is a drug delivery system with high safety, high targeting, and a wide range of applications.

The invention relates to the technical field of fusion membrane nano preparations, and provides a nano preparation capable of being used for cerebral arterial thrombosis gene drug targeted delivery, which comprises lipid-calcium phosphate nanoparticles, which are composed of DOPA modified calcium phosphate cores and lipidosome and are used for providing positive charges to obtain efficient gene loading efficiency and proton sponge effect, the intracellular efficient delivery and release of the gene are realized; and the exosome membrane is prepared from a cell culture solution extracted from bone marrow-derived mesenchymal stem cells and is used for improving the transfection efficiency of the carried medicine. According to the present invention, by using the process characteristic that the inner layer phospholipid and the outer layer phospholipid are not synchronously prepared during the LCP preparation process, the biological membrane of the exosome and the LCP outer layer phospholipid are fused during the LCP preparation of the outer layer phospholipid so as to construct the fusion membrane preparation having the characteristics of the biological membrane and capable of carrying out AMD3100 targeting modification, such that the advantages of the biological membrane and the AMD3100 in the targeting delivery system are combined so as to achieve the target delivery effect; and the bottleneck of drug delivery for brain diseases is solved.

The disclosure describes novel systems, methods, and compositions for the manipulation of nucleic acids in a targeted fashion. The disclosure describes non-naturally occurring, engineered CRISPR systems, components, and methods for targeted modification of nucleic acids such as DNA. Each system includes one or more protein components and one or more nucleic acid components that together target nucleic acids.

The invention discloses a modified exosome as well as a preparation method and application thereof, and relates to the technical field of biological medicines, CD44 targeted modification and composite active ingredients are synergistic to realize efficient repair of burn wounds and sensitive skin, and the modified exosome can be specifically enriched on the burn wounds or damaged sensitive skin parts through CD44 targeted peptide fragment coupling, so that the effect of repairing the burn wounds and the sensitive skin is achieved. The defects that a traditional repairing product is poor in targeting property and low in active ingredient utilization rate are overcome, the loaded dipotassium glycyrrhizinate, glutathione and FGF form a synergistic effect, wound healing and skin barrier repairing can be promoted through the FGF, the dipotassium glycyrrhizinate and the glutathione can be used for strongly resisting inflammation and oxidation, release of sensitive skin inflammatory factors is reduced, and the repairing effect is achieved. By matching with nitrogen protection incubation and a pulse ultrasonic loading process, the stability of active ingredients is greatly improved, finally, the repair effects that the healing process of burn wounds is remarkably accelerated, and sensitive skin percutaneous moisture loss is obviously reduced are achieved, and safety and effectiveness are both considered.

The application discloses a kind of targeted drug-loaded nanoparticles response release performance detection method, specifically related to targeted nano-drug detection field, for solving the problem that only according to single release curve in the release performance detection of existing targeted drug-loaded nanoparticles, it is difficult to distinguish ordinary environment early leakage, insufficient release of channel plugging and stimulation response release. By generating a structure reference record containing initial drug loading, targeting modification amount and channel plugging state, and dividing the homologous sample into unmodified drug-loaded control group, targeted drug-loaded detection group and targeted modification blank correction group, and then combining the non-stimulation leakage curve, the stimulation switching release curve and the corrected release curve, the effect of distinguishing early leakage, stimulation response release and channel plugging effect is achieved, so that the detection result more accurately reflects the plugging leakage reduction ability and stimulation release ability of targeted drug-loaded nanoparticles.

The present disclosure provides a recombinant Cas9 protein with a faster degradation rate than wild-type Cas9. The present disclosure also provides a recombinant Cas9 protein and a CRISPR-Cas system with reduced off-target modifications. Also provided herein is a method for site-specific modification with reduced off-target modifications using the recombinant Cas9 protein of the present disclosure.

The invention relates to a full-process digital management method and system for a project design link. The method comprises the following steps: editing a project design document in a project process on line; integrating the project design documents, associating various project design documents based on demand BRP, and digitally penetrating various project design documents by taking function points as base points; various project design documents are disassembled and integrated, and digital assets are precipitated in a system dimension; and performing targeted modification and updating based on the function points, and multiplexing the digital assets through the function points and the associated contents of the function points. According to the method, demand design, development scheme design and test scheme design in the research and development process are managed in a centralized mode, full-process digital management of design research and development links is achieved, design assets in the management process are split and integrated according to system dimensions, and design asset precipitation and reuse of the system dimensions are achieved.

The invention belongs to the technical field of biology and medicine, and particularly relates to a tumor targeted photo-thermal chemotherapy drug delivery system and a preparation method and application thereof. According to the tumor targeted photo-thermal chemotherapy drug delivery system provided by the invention, a core carrier adopts a black phosphorus nanosheet (BPNS) and ferroferric oxide (Fe3O4) composite structure, BPNS generates heat under irradiation of near-infrared light to realize photo-thermal therapy, and Fe3O4 endows a magnetic targeting function; the medicine part is a ferroptosis inducer RSL3, glutathione (GSH) is reduced and reactive oxygen species (ROS) is increased through an inhibition system Xc-, and tumor cell ferroptosis is induced; the targeting modification layer is liver cancer cell membrane protein (Pro), and liver cancer cell surface receptors are specifically recognized through a homologous targeting mechanism, so that the enrichment efficiency of drugs in tumor tissues is improved. The system can significantly improve the treatment effect and reduce the toxicity to normal tissues, and provides a new solution for liver cancer treatment.

The invention discloses a nano-drug for promoting cupric death of tumor cells and a preparation method of the nano-drug. The nano-drug comprises hyaluronic acid; a dopamine; copper ions; a diethyldithiocarbamic acid-copper conjugate; and a method for preparing the same. A peptide fragment with a targeting function; modifying a thiol ligand; the preparation method comprises the following steps: preparing a diethyl dithiocarbamic acid-copper conjugate, forming a nano-structure inner core, wrapping the conjugate, forming a copper ion protection layer, and purifying and carrying out targeted modification on a nano-drug. The preparation method comprises the following steps of: preparing the diethyl dithiocarbamic acid-copper conjugate, forming a nano-structure inner core, wrapping the conjugate, forming a copper ion protection layer, and carrying out targeted modification on the nano-drug. The copper ions are further fixed through the coordination effect of dopamine and the copper ions, wrapping of the diethyl dithiocarbamic acid-copper conjugate and the thiol-copper coordination effect of the modified thiol ligands, so that a double-coordination mechanism is formed, the loading capacity of the copper ions in the nano-drug is remarkably improved, and the stability of the nano-drug is improved. The copper death of tumor cells can be more effectively triggered, the copper ion loading capacity can be improved, and a material basis is provided for the efficient copper death effect.

The invention provides a retina photosensitive neuronal lesion zebrafish model and a construction method thereof, and relates to the technical field of gene engineering. Wherein the sgRNA comprises a guide sequence which can specifically recognize and be combined with a nucleotide sequence shown as SEQ ID NO.4 in an elovl2 gene. The high specificity of the sgRNA ensures the precise targeted modification of the elovl2 gene, and obviously reduces the off-target risk. The genetic background of the constructed zebrafish model is clear, and the retinopathy phenotype can be reliably attributed to the lovl2 gene mutation, so that a stable biological tool which is highly similar to human diseases is provided for related disease research and drug screening.

The invention discloses a precise editing method of a gamma-PGA high-yield strain based on CRISPR-Cas9n, and relates to the technical field of high-yield strains. According to the invention, a CRISPR-Cas9n double-nickase system is adopted, and adjacent DNA nicks are generated through the synergistic effect of double sgRNA, so that the non-specific cutting risk is greatly reduced; the double sgRNA targeting design is combined with a homologous recombination template, so that directional editing of key genes is realized, the homologous recombination efficiency reaches 75 + / -5%, and target modification is ensured to be stably integrated into a genome; by virtue of a PEG-mediated protoplast conversion method, the limitation of low efficiency of traditional electrotransfection is overcome, and the CRISPR carrier is rapidly removed in combination with a temperature-sensitive plasmid elimination system, so that cytotoxicity caused by continuous expression is avoided; under optimized fermentation conditions, the gamma-PGA yield of the edited strain reaches 15 + / -2g / L and is increased by 200% compared with that of the original strain.

The disclosure describes novel systems, methods, and compositions for the manipulation of nucleic acids in a targeted fashion. The disclosure describes non-naturally occurring, engineered CRISPR-Cas systems, components, and methods for targeted modification of nucleic acids such as DNA. Each system includes one or more protein components and one or more nucleic acid components that together target nucleic acids.