125 results about "Disease mechanisms" patented technology

The invention provides a protein methylation site prediction method fusing quantum and region perception, which comprises the following steps: step 1, acquiring a protein sequence as a data source, and respectively constructing a training set and an independent test set; 2, constructing a multi-modal feature for each protein sequence by adopting a three-way nested scattering network, and fusing the multi-modal features to obtain an optimized fusion feature tensor; and step 3, inputting the optimized fusion feature tensor into a RaQMeNet network model, and performing a methylation site prediction task. The performance indexes of the method are greatly superior to those of the prior art, and the method has higher adaptability, stability and interpretability, can be widely applied to a plurality of bioinformatics and biological medicine related fields such as protein function annotation, disease mechanism research and drug target discovery, and has good application prospects and commercial values.

The invention relates to a data fusion processing method and system for an intelligent sensor based on MEMS, and the method comprises the following steps: carrying out the non-stationary signal decomposition of a multi-modal physiological parameter time sequence data stream, and obtaining a key vital sign feature sequence; performing phase coupling degree calculation on the key vital sign feature sequence to obtain an inter-organ function correlation intensity matrix; performing high-dimensional feature space projection on the critical patient based on the inter-organ function association intensity matrix to obtain a pathological state feature map of the patient; performing nonlinear kinetic analysis on the pathological state characteristic spectrum of the patient to obtain a disease progress dynamic trajectory; and performing clinical decision support reasoning based on the disease progress dynamic trajectory to obtain personalized treatment suggestions, thereby solving the technical problem that the existing analysis method is often limited to observation of a single physiological parameter or simple statistical analysis and lacks the ability to understand the disease mechanism from the overall perspective.

The invention discloses an E3 ubiquitin enzyme mutant as well as modification and a protein targeted degradation system and application thereof, and particularly relates to a series of targeted protein degradation enhanced E3 ubiquitin enzymes (Trim21-N) and a modification method thereof, the E3 ubiquitin enzymes (Trim21-N) are obtained by modifying a wild type Trim21 (wtTrim21) protein structural domain, and the E3 ubiquitin enzymes comprise Trim21-a, Trim21-b, Trim21-c, Trim21-d, Trim21-e and Trim21-f. The efficiency of degrading the target protein through the ubiquitin proteasome is remarkably improved, and the method has the characteristics of strong endogenous and exogenous universality, high specificity, ubiquitin proteasome dependence, low cytotoxicity, strong cell compatibility and the like on the degradation of the target protein. The invention provides E3 ubiquitin enzyme (Trim21-N) based on a targeted protein degradation enhancement version and an exogenous fluorescence report degradation system of the E3 ubiquitin enzyme (Trim21-N), preferably Trim21-e with the optimal degradation effect, and the E3 ubiquitin enzyme (Trim21-N) is named as delta Trim21. The invention further provides an endogenous protein degradation system based on the delta Trim21. The method has the characteristics of high specificity, rapidness and small module, so that the method can be used for researching various biological and disease mechanisms, including the fields of cell targeted therapy, cell mechanism exploration, genetic engineering and the like.

The invention discloses a differential gene regulation and control network reconstruction method based on mutual information and a redundancy regulation and control filtering system. The method comprises the following steps: firstly, collecting gene expression data under two or more conditions, respectively calculating mutual information of gene pairs under each condition, and screening the gene pairs with obvious mutual information difference as candidate regulation edges; furthermore, a redundancy regulation and control relation caused by the intermediary variables is identified and eliminated through calculation condition mutual information, and finally a difference regulation and control network with high credibility is constructed. The system comprises a data preprocessing module, a mutual information calculation module, a redundancy indirect regulation and control effect filtering module, a regulation and control direction judgment module, a network construction and threshold optimization module, a difference network construction module and an output and visualization module. The method can effectively improve the biological interpretability and inference accuracy of the network, and is widely applied to the bioinformatics fields such as disease mechanism research, regulatory factor identification and multi-omics integrated analysis.

The invention belongs to the field of biological genetic engineering, and particularly relates to a method for constructing a congenital heart disease mouse model. The invention provides gRNA (guide Ribonucleic Acid) for targeting a mouse Tmed1 gene. Nucleotide sequences of the gRNA are as shown in SEQ ID NO: 1 and SEQ ID NO: 2. Meanwhile, the invention provides a method for knocking out the mouse Tmed1 gene based on a CRISPR / Cas9 technology to obtain the mouse with the congenital heart disease. The Tmed1 mouse model is successfully constructed, a reliable mouse model is provided for congenital heart disease and visceral ectopic syndrome patients, subsequent detection and verification of upstream and downstream target gene functions and subsequent verification of development of related target drugs are facilitated, and great convenience is brought to disease mechanism research and drug research and development verification work.

The invention provides a brain disease drug curative effect analysis and prediction system and method, and relates to the technical field of drug analysis. Multi-source heterogeneous data such as genetic variation spectrum, neural image topological characteristics, metabolic trajectory vectors and microbiome dynamic distribution matrix are integrated, and cross-modal dynamic fusion is realized through decomposition. The system constructs a drug prediction coupling network based on dynamic causal inference, analyzes overlapped potential intervention nodes of multiple disease mechanisms, and generates a disease-drug-phenotype multi-dimensional mapping library. A short-term drug response toxicity threshold is predicted through a metabolic entropy change model, a long-term neurological function degeneration trajectory is evaluated in combination with epigenetic drift, and an anti-fact strategy gradient is utilized to dynamically optimize a drug administration scheme. According to the invention, accurate fusion and dynamic analysis of multi-modal data are realized, a balance mechanism of curative effect and risk is established, and accurate drug combination sequence and administration strategy support can be provided for individualized treatment of complex brain diseases.

The invention discloses a screening method of sicca syndrome markers based on conjunctival blotting, and relates to the technical field of biomedicine, and the screening method comprises the following steps: S1, conjunctival noninvasive sampling; s2, RNA (Ribonucleic Acid) sequencing and pathway screening; s3, machine learning modeling is carried out; s4, clinical verification. According to the invention, biomarker screening is realized, and similar biomarker screening can also be realized through tear sample analysis or other ophthalmic samples; however, the alternative schemes have the defects of relatively strong invasiveness, complex operation and the like; sampling is carried out through the conjunctival imprinting technology, invasive operation such as biopsy and blood drawing is avoided, and pain and discomfort are reduced; differential expression genes can be accurately identified, and the sensitivity and the accuracy are relatively high; through immune cell infiltration analysis, the relationship between the immune cell subpopulation and the sicca syndrome related gene is disclosed, a new perspective is provided for a disease mechanism, and a theoretical basis is provided for a future immune regulation strategy.

The present invention relates to a data fusion processing method and system for an MEMS-based intelligent sensor, including the following steps: decomposing the multi-modal physiological parameter time series data stream to obtain a key vital sign feature sequence; calculating the phase coupling degree of the key vital sign feature sequence to obtain an organ-interfunction association strength matrix; performing high-dimensional feature space projection on the critically ill patient based on the organ-interfunction association strength matrix to obtain a patient pathological state feature map; performing non-linear dynamics analysis on the patient pathological state feature map to obtain a disease progression dynamic trajectory; and performing clinical decision support reasoning based on the disease progression dynamic trajectory to obtain personalized treatment recommendations, solving the technical problem that existing analysis methods are often limited to the observation of a single physiological parameter or simple statistical analysis and lack the ability to understand the disease mechanism from an overall perspective.

The invention belongs to the technical field of liquid-liquid phase separation, and particularly relates to a novel method for controlling liquid-liquid phase change of biomolecules by using a magnetic field, which uses the magnetic field to control liquid-liquid phase change separation of the biomolecules without any additive. The method has non-invasive and remote specificity, does not need to add any additive, is especially used in living cells, does not damage the living cells, and provides a new tool for researching cell functions and disease mechanisms.

The invention relates to the technical field of biology, and discloses a construction method of a gastric cancer organoid culture system, which comprises the following steps: preparation of a conditioned medium: culturing L-WRN cells and collecting the conditioned medium; preparing a gastric cancer organoid culture medium, and mixing the conditioned culture medium, the basic culture medium, a plurality of growth factors and additives; and extraction and culture of organoid: separating cells from gastric cancer tissues, mixing the cells with matrigel, and culturing by using the prepared culture medium. According to the method, the repeatability and the stability of the organoid model are improved, the response consistency of the organoid in drug screening is improved, and the reliability of the model in disease mechanism research and personalized medical application is guaranteed.

The invention discloses a construction method and application of a Lewy small body dementia animal model, and belongs to the technical field of animal model construction. The construction method comprises the following steps: obtaining a phosphatase and tensin homologous gene-induced kinase 1 gene knockout experimental animal A by using a gene editing technology, and carrying out hybrid breeding on the experimental animal A and an Alzheimer disease model experimental animal B simulating beta-amyloid protein (Abeta) pathology, and screening filial generations containing the Alzheimer disease related mutation and pink1 gene knockout at the same time. According to the constructed model, beta amyloid protein is deposited on the basis of pink1 gene knockout, beta-amyloid plaque (A beta) is used for inducing alpha-synuclein protein aggregation, Lewy bodies are widely generated in cortex and hippocampus, the occurrence and development process of DLB is simulated, and a reliable animal model is provided for disease mechanism research and treatment drug screening and development.

The invention belongs to the technical field of traditional Chinese medicine and biological medicine, and provides a pharmaceutical composition SGD for improving sepsis acute kidney injury and a preparation method and application thereof, the pharmaceutical composition SGD is prepared from the following raw materials by weight: 25-35 parts of raw white peony root, 8-13 parts of honey-fried licorice root, 10-20 parts of winged euonymus twig, 10-20 parts of caulis sinomenii, 25-35 parts of lalang grass rhizome, 8-13 parts of patrinia and 8-13 parts of sargentgloryvine stem. The SGD is used for treating S-AKI for the first time, on one hand, the SGD reduces oxidative stress and systemic inflammatory response by inhibiting a PI3K-AKT signal channel, on the other hand, the SGD can improve the renal function of S-AKI and the survival rate of mice, and participates in regulating the disease mechanism of S-AKI. The potential protection effect of the SGD on S-AKI, systemic inflammation and oxidative stress is discussed, and the protection mechanism of the SGD is further discussed by paying attention to a PI3K-AKT signaling pathway. And further evidence can be provided for SGD treatment of S-AKI.

The invention provides an ovarian cancer monitoring system based on iron metabolism related protein, comprising: an information monitoring module for monitoring iron metabolism protein index data and ovarian cancer core biomarker index data of a user; the abnormality determination module is used for comparing the iron metabolism protein index data and the ovarian cancer core biomarker index data with historical personal baselines of the current ovarian cancer development stage of the user, determining the variation amplitude, and triggering the ovarian cancer analysis module to perform analysis when the variation amplitude meets preset requirements; and the ovarian cancer analysis module is used for updating the ovarian cancer risk index grade based on the iron metabolism protein index data of the user and the ovarian cancer core biomarker data. According to the invention, the iron metabolism protein index is combined with the ovarian cancer core biomarker, and the biological characteristic of iron-dependent proliferation of the ovarian cancer cells is utilized, so that an index basis which is more suitable for a disease mechanism is provided for monitoring, and the possibility of early abnormality capture is improved.

This invention belongs to the field of vertebrate technology, specifically relating to a method for constructing a complex inflammatory animal model in middle-aged and elderly individuals and its related applications. The method includes: selecting adult animals for adaptive feeding, daily subcutaneous injection of D-galactose to establish a susceptibility to aging and oxidative stress, and administering sodium dextran sulfate (DSS) solution within a specific time window to induce intestinal inflammation, forming a complex inflammatory state through gut-hepatic axis interactions. The constructed animal model simultaneously exhibits intestinal inflammatory damage, abnormal hepatic oxidative stress, and aging-related characteristics, realistically simulating the pathological process of gut-hepatic axis dysfunction in middle-aged and elderly individuals. This model is suitable for screening and evaluating drugs, medical nutrition products, and functional foods that improve gut-hepatic axis dysfunction, providing a reliable technical platform for research on related disease mechanisms and the development of interventional substances.

The invention discloses a culture medium for colonization of intestinal flora and intestinal gas of people with hyperuricemia. The culture medium contains yeast extract, ethanol, adenine, tryptone, mucoprotein, mycoprotein, insect protein, soybean protein, fructose, glucose, inulin, resistant dextrin, dietary fiber, oxalic acid, saturated fatty acid, sialic acid, peanut oil, potassium chloride, sodium chloride, monopotassium phosphate, sodium sulfate, bile salt, cysteine hydrochloride and a plant extract mixture. Vitamin mixed liquid and the like. By means of the bionic colon reactor, by referring to real in-vivo parameters of people suffering from hyperuricemia, the real intestinal environment of people suffering from hyperuricemia in China is well simulated in vitro, the intestinal flora ecology and intestinal gas distribution are reproduced, and a normal intestinal microorganism and intestinal gas database of people suffering from hyperuricemia can be constructed. The method is beneficial to accurate diagnosis of intestinal microecology of people with hyperuricemia, individualized treatment of antisense booking and disease mechanisms, better maintenance of intestinal health and formulation of preventive measures.

The present invention relates to a culture medium, a method for culturing polycystic kidney organoids and an application thereof. The present invention uses the renal pathological cyst wall tissue of ADPKD patients as the cell source, and constructs 3D organoids of polycystic kidney through RGF culture medium. The 3D organoids have better genetic stability and can better simulate the pathological characteristics of ADPKD in vivo. In order to enhance the vesiculation state of the above 3D organoids and better simulate the physiological state of diseased tissues, the present invention introduces Forskolin and applies the organoids to the construction of a drug screening model. After screening, GSK2193874 can significantly inhibit the vesicle growth of polycystic kidney organoids, suggesting its potential application in the preparation of therapeutic drugs for polycystic kidney disease. The above culture method is applied to the in vitro culture of ADPKD polycystic kidney organoids, and is expected to be used for disease mechanism research, drug screening and clinical cell therapy after correction, etc.

The invention discloses a single molecule positioning method based on deep learning feature fusion, and the method comprises the following modules: a data processing module which uses an analog number sample generated by imageJ as a training set, and converts a generated positioning table into a corresponding image as a verification set; the Resnet module is used for extracting the characteristics of the data; the ASF module is a feature fusion module and is used for fusing features of different scales according to different weights; and the attention mechanism module can selectively pay attention to the positioning information of the single molecule and is beneficial to realizing more accurate positioning on the single molecule. According to the technology, the super-resolution positioning of the single molecule is completed through the deep learning network, and the accurate positioning of the single molecule image can be quickly formed. The technology not only is helpful to research and track experiments of single molecule dynamic behaviors, but also has a wide prospect in the aspects of assisting accurate analysis and early diagnosis of disease mechanisms.

The invention relates to the technical field of medical education and biological information visualization, in particular to a disease mechanism-associated protein structure and function visualization teaching virtual simulation system, which comprises a data storage module, a structure calling visualization module, a function-disease association module, an interactive operation module and a teaching evaluation module, all the modules interact through data interfaces. According to the protein structure and function visual teaching virtual simulation system associated with the disease mechanism, deep association of a protein three-dimensional structure, a function mechanism and a disease case is realized for the first time, the knowledge splitting barrier of traditional teaching is broken, and students are helped to construct a complete cognitive chain; autonomous operation and mutation simulation are supported, an abstract structure function relation is converted into an interactive visual model, the learning difficulty is remarkably reduced, and the knowledge absorption rate is increased; an experiment task and evaluation system is built in, a teaching closed loop of preview-operation-assessment-feedback is achieved, and the requirement for large-scale medical talent training is met.

The invention relates to the technical field of molecular immunology and biology, in particular to a sicca syndrome model mouse B cell immune repertoire sequencing and subpopulation analysis method. The method comprises the following steps: S1, sample preparation: preparing a single-cell suspension from a target autoimmune disease animal model and a preset tissue of a control animal, and carrying out B cell enrichment treatment on the single-cell suspension to obtain a B cell sample; s2, multi-dimensional data parallel analysis: analyzing the B cell sample, and performing parallel construction of the multi-dimensional data; and S3, integrated correlation analysis: carrying out correlation analysis on the immune group library data, the cell subset data and the signal channel data obtained in the step S2 to establish a correlation relationship among specific B cell cloning characteristics, specific B cell subset changes and specific signal channel activity, and carrying out multilevel analysis and generating a B cell immune response mechanism of the autoimmune disease. The efficiency and accuracy of disease mechanism research and drug action mechanism evaluation are remarkably improved.

Embodiments of the instant disclosure relate to an in vitro system for generating 3D skin equivalent, compositions, and methods for modeling and analyzing potential therapeutic treatments of Ehlers-Danlos Syndrome (EDS), including personalized therapies and regimens. In certain embodiments, the in vitro system can be utilized to facilitate diagnosis, drug discovery, investigation of disease mechanisms, and treatment of EDS and other connective tissue diseases. In certain embodiments, compositions, and methods for making and using matrix metalloproteinase 9 (MMP-9) inhibitors are disclosed to treat EDS. In some embodiments, a subject has hypermobility type EDS (hEDS).

The invention relates to the technical field of molecular biology and precision medical treatment, and relates to a molecular marker for predicting FOLFOX chemosensitivity and application thereof. A patient-derived colorectal cancer organoid biological sample library is constructed, the heterogeneity of in-vitro drug reaction is analyzed and evaluated through transcriptome, clinical groups sensitive to FOLFOX chemotherapy can be accurately recognized, a molecular marker prediction system containing 11 genes is obtained through further screening, and the molecular marker prediction system is used for predicting the FOLFOX chemotherapy. The method effectively overcomes the technical defect of lack of accurate prediction of colorectal cancer chemosensitivity at present, and has important value in the aspects of revealing disease mechanisms and guiding personalized treatment.

The system according to this embodiment aims to analyze gene expression data, predict disease mechanisms, and generate new research hypotheses. [Solution] The system according to the embodiment comprises an acquisition unit, an analysis unit, a prediction unit, a hypothesis generation unit, a treatment method proposal unit, and a report generation unit. The acquisition unit acquires gene expression data. The analysis unit analyzes the gene expression data acquired by the acquisition unit. The prediction unit predicts the disease mechanism based on the data analyzed by the analysis unit. The hypothesis generation unit generates a new research hypothesis based on the prediction results obtained by the prediction unit. The treatment method proposal unit proposes the optimal treatment method based on the hypothesis generated by the hypothesis generation unit. The report generation unit generates an experimental result as a report based on the treatment method proposed by the treatment method proposal unit.

The separation and detection method comprises the following steps: rinsing placenta or villus tissues in a PBS (Phosphate Buffer Solution) added with a 1% penicillin-streptomycin double antibody solution, digesting the placenta or villus tissues into single cells by using a 1640 culture medium containing I-type and IV-type collagenase after the placenta or villus tissues are rinsed sufficiently to obtain a cell suspension, and culturing the cell suspension for later use; diluting and neutralizing collagenase digestive juice by using a 1640 culture medium containing high-temperature heat-inactivated fetal calf serum according to 5 times of volume; repeatedly discarding the precipitate, recovering the supernatant, and centrifuging to obtain a coarse migration body; and establishing a density gradient by using Optiprep as a density medium, washing the precipitate with PBS, and centrifuging to obtain the trophoblast cell-derived transporter. The invention provides a group of placenta villus trophoblast cell source migration body specific expression membrane proteins for the first time, and provides a method for specifically capturing the placenta trophoblast source migration body on the basis of the placenta villus trophoblast cell source migration body specific expression membrane proteins, so that a new direction for researching a trophoblast dysfunction related disease mechanism can be enriched.

This invention relates to a method for disease therapeutic target discovery and drug prediction based on multi-omics networks and deep learning models, belonging to the interdisciplinary field of bioinformatics and artificial intelligence drug discovery. The method includes: integrating genomic expression profiles and common molecular interaction data from disease and control groups to construct a candidate whole-genome network; refining the network based on expression profile data through systematic modeling and the AIC criterion to obtain the real molecular interaction network; extracting the core network using the master network projection method and identifying key targets through pathway analysis; predicting candidate drugs interacting with the targets using a pre-trained deep neural network model; and finally screening potential therapeutic drugs based on multi-dimensional criteria such as regulatory ability, sensitivity, and toxicity. This invention achieves a complete integration from disease mechanism analysis to drug prediction, and is particularly suitable for complex diseases such as atopic dermatitis. It can systematically discover precise targets and efficiently predict repositionable drugs, significantly improving R&D efficiency.

Provided in the present invention is a new 3D microtissue model based on tissue microenvironment reduction. Specifically, provided in the present invention is the use of a cytokine combination in the promotion of the growth of a tumor 3D micromicrotissue model, wherein the cytokine combination is selected from at least two of IL-6, Gremlin-1, FGF2, HGF and IGF-1. The combination of cytokines can promote the proliferation, differentiation and tissue formation of a tumor microtissue model to obtain more microtissue models with larger volumes, so that the growth microenvironment of a tumor can be reproduced in a more realistic manner, and a more comprehensive tool is provided for the subsequent research of disease mechanisms and the screening and development of drugs.

The invention discloses a state recognition method of an adaptive gene editing laboratory mouse, and aims to solve the problem of insufficient state recognition specificity of the gene editing laboratory mouse in the prior art. The method comprises the following steps: acquiring genotypes, disease model types and experimental environment parameters of laboratory mice; optimizing detection and optical flow analysis parameters, generating a time sequence behavior track map and segmenting a key area; extracting general and pathological specific composite features and standardizing the general and pathological specific composite features; calling a genotype pathological feature association database to calibrate a weight and a threshold value, and inputting a random forest classifier recognition state of transfer learning optimization; scores are calculated through a weighted scoring model, the state is judged, and credibility is calculated through a multi-dimensional confidence evaluation model. The method is suitable for various gene editing laboratory mice and experimental environments, the accuracy and suitability of state recognition are improved, and powerful support is provided for gene therapy research and development and disease mechanism research.

The application discloses a virtual cell analysis platform based on cell disturbance data. The platform comprises three parts: a large language model data preprocessing system, a database and an online analysis platform, and a direction matching algorithm. The large language model data preprocessing system comprises an automatic data information extraction and retrieval tool, an automatic data file download tool, a large language model analysis engine and a gene expression data acquisition and feature extraction tool. The application can automatically preprocess the original data by applying the large language model data preprocessing system to the target scientific problem, and then store the data in the database. The characteristic direction matching algorithm is combined to output the drugs and key targets related to the target data set. The efficiency of target point and drug screening is improved. The application is suitable for large-scale omics data mining and disturbance analysis, accelerates the drug research and development, disease mechanism and translational medicine research process, and reduces the research and development cost.

The invention provides a biological sample system for clinical tests. Comprising a sample identification and tracking end, a sample acquisition and processing planning end and a sample storage and inventory management end. The biological sample system plays an important role in a clinical test, and the biological sample system for the clinical test ensures the quality and traceability of a sample and the reliability of data. According to the biological sample system for the clinical test, by effectively managing biological samples, researchers can obtain accurate test results, better understand disease mechanisms, evaluate drug curative effects, find new biomarkers and the like. In addition, the biological sample system should follow ethical specifications and supervision requirements, and rights and interests and privacy of test participants are protected.

The application discloses a virtual cell analysis platform based on cell disturbance data. The platform comprises three parts: a large language model data preprocessing system, a database and an online analysis platform, and a direction matching algorithm. The large language model data preprocessing system comprises an automatic data information extraction and retrieval tool, an automatic data file download tool, a large language model analysis engine and a gene expression data acquisition and feature extraction tool. The application can automatically preprocess the original data by applying the large language model data preprocessing system to the target scientific problem, and then store the data in the database. The characteristic direction matching algorithm is combined to output the drugs and key targets related to the target data set. The efficiency of target point and drug screening is improved. The application is suitable for large-scale omics data mining and disturbance analysis, accelerates the drug research and development, disease mechanism and translational medicine research process, and reduces the research and development cost.

The invention discloses application of double-mutant zebrafish in preparation of a mast cell function defect animal model. The double-mutant zebra fish disclosed by the invention is cpa1- / -cpa5- / -double-mutant zebra fish, and is obtained by further knocking out a cpa1 gene on the basis of a cpa5- / -zebra fish mutant. According to the method, potential compensation effects of two key carboxypeptidases are eliminated at the same time, and the storage and release capacity of mast cell protease is remarkably weakened from the genetics level, so that the zebrafish animal model with the mast cell function defect, which is clear in phenotype and stable in function, is obtained. The animal model can be used for mast cell function mechanism research, related disease mechanism exploration and drug screening and evaluation, and has a good application prospect.