251 results about "TOLLIP" patented technology

The invention provides a drug-disease association prediction method and system, computer equipment and a medium, and belongs to the technical field of computers. The method comprises the following steps: constructing a drug-protein-disease heterogeneous network, and extracting a plurality of element path sub-graphs; inputting the meta-path sub-graph into a multi-scale diffusion graph convolution module, executing learnable multi-step graph diffusion on the basis of graph convolution, synchronously capturing local adjacency and high-order topological information, and generating node embedding; and performing dynamic weighted fusion by utilizing meta-path attention to obtain unified representation. In order to relieve imbalance of positive and negative samples, implementing difficult negative sampling in the embedding space, and constructing a balance training set with the positive samples; medicine-disease features are spliced, a regularization XGBoost classifier is trained, and unknown correlation accurate prediction is achieved. By adopting the method, the drug-disease association prediction precision and efficiency are improved, multi-scale topology and priori knowledge are fused, and a powerful calculation tool is provided for drug relocation.

The invention discloses a disease risk assessment method and screening device based on a multi-group student physical collaborative digital network, and relates to the field of intelligent medical detection. In order to solve the defect that multi-omics-level system collaborative analysis and robust risk assessment are difficult to realize in the prior art, the technical scheme provided by the invention is as follows: acquiring a plasma sample, acquiring a spectral signal by adopting an attenuated total reflection Fourier transform infrared spectrum, and establishing a plasma spectrum digital information space; the method comprises the following steps: constructing a biological collaborative digital network containing four nodes of protein, lipid, saccharides and nucleic acid based on pathophysiology priori knowledge, and defining node strength, edge weight and network collaborative efficiency; a health baseline configuration file is established by using a health sample, a standardized deviation score of a to-be-tested sample is calculated, a comprehensive risk score is obtained, a disease screening result is output in combination with a machine learning model, and digital evaluation of multi-omics collaborative characteristics is realized. The method is suitable for non-invasive rapid screening and risk assessment work of neurodegenerative diseases and mental diseases.

The present invention relates to a novel regulatory element. The regulatory element according to one embodiment is capable of increasing RNA stability or mRNA translation of a transcription product of a target gene, thereby being capable of increasing the expression level of the target protein, and can be effectively used in systems requiring precise control of gene expression, such as gene therapy, vaccine development, and production of protein therapeutics. Furthermore, the regulatory element of the present application exhibits excellent stability-increasing ability and translation-regulating ability not only in unmodified RNA but also in RNA containing a modified base, and thus can be effectively used in therapeutic mRNA or vaccine platforms requiring base modification.

The invention belongs to the technical field of gene identification, and discloses a method for integrating multi-omics data to enhance genome prediction and candidate gene identification, candidate gene identification is verified through multi-layer evidence integration, and the verification comprises priority ordering based on gene contribution scores, function enrichment analysis, generic genome network verification and CRISPR / Cas9 experimental verification. Evaluation on a corn population (n = 174) containing complete genomics, transcriptomics, translational omics and proteomics maps shows that the framework is remarkably improved in grain character prediction and is improved by 2.9-12.3% compared with a genome selection baseline, and meanwhile candidate genes verified by experiments are recognized. The invention further verifies the universality of the framework to five traits on an arabidopsis thaliana population, and provides an open source software platform to promote the practical application of the framework in a breeding plan.

The invention discloses a multi-layer heterogeneous network unicellular organism network inference method based on meta-path enhancement, which mainly comprises a gene regulation knowledge base enhanced multi-layer heterogeneous network construction module for integrating an external gene interaction network and multiple omics data such as scRNA-seq, scATAC-seq, ST and the like; constructing a single-cell multi-omics multilayer heterogeneous network containing cell-cell, cell-gene and gene-gene relationships, and fusing spatial constraints to consider cell positions and tissue structures; and the feature enhancement module based on the meta-path explores complex semantics of the network by designing a multi-hop meta-path mode, designs an adaptive multi-view learning framework and a multi-round enhancement mechanism, and optimizes feature representation by using cell-gene interaction and cross-modal attention fusion. The unicellular biological network can be effectively deduced, the deduction accuracy and biological interpretation are remarkably improved, the method plays an important role in understanding the cell biological process, developing and treating diseases and the like, has good expandability, and can further integrate multi-modal omics data such as proteomics and metabonomics.

Provided herein are engineered Epstein-Barr virus nuclear antigen 1 (EBNA1), coding molecules thereof, vectors and mammalian cell expression systems comprising the same, and polypeptide of interest recombinantly produced by the foregoing. Also provided are methods for the preparation of the engineered EBNAls, coding molecules thereof, vectors and mammalian cell expression systems and methods for using the same in recombinant expression.

The application provides a method for analyzing the synergistic mechanism of hepatotoxicity and nephrotoxicity of non-steroidal anti-inflammatory drugs. The method comprises the following steps: preliminary toxicity prediction of NSAIDs and collection of toxicity target points, collection of liver and kidney disease target points, then cross and screening of the target points to obtain core target points and common core target points of NSAIDs induced liver and kidney diseases, and then constructing a protein interaction network of the common core target points; enrichment analysis of the common core target points to obtain the common action pathway of NSAIDs induced liver and kidney diseases; finally, further screening of the common core target points to obtain the key target points of NSAIDs induced liver and kidney diseases, and verification by using molecular docking technology. Compared with the traditional method, the advantages of the method are: first, the method does not depend on large-scale patient clinical data and a large number of animal or cell experiments, avoiding the ethical controversy in animal experiments and human experiments; second, the method can identify the potential cross-pathway and synergistic toxicity mechanism when a compound triggers multiple diseases, which is helpful for more comprehensive evaluation of the toxicity risk of NSAIDs.

The embodiment of the invention provides a drug optimization method and system based on the overall effect of a protein network. The method comprises the following steps: constructing a protein interaction network related to a target disease, and dividing each protein target into a risk protein set and a protection protein set; respectively calculating first binding affinity data of the candidate drugs and each protein target in the risk protein set, and generating a first network comprehensive score based on the first binding affinity data; respectively calculating second binding affinity data of the candidate drugs and each protein target in the protection protein set, and generating a second network comprehensive score based on the second binding affinity data; calculating network confrontation scores of the candidate drugs according to the first network comprehensive score and the second network comprehensive score; and determining whether the candidate drug is a preferred drug based on the network adversarial score. The method can overcome the defect that a single-target drug is insufficient in curative effect due to a network compensation effect, so that safer and more effective candidate drugs are screened out.

Disclosed is a novel class of fusion proteins to recruit the cell's innate chaperone machinery, specifically the Hsp70-mediated system, to specifically reduce TDP-43-mediated protein aggregation and associated protein conformational diseases.

The invention discloses a 5-bromoindole-2-carboxylic acid methyl ester derivative as well as a preparation method and application thereof in a protein inhibitor, and relates to the technical field of synthesis and preparation of inhibitors. According to the 5-bromoindole-2-carboxylic acid methyl ester derivative, compared with a contrast product, the synthetic route steps of the prepared 5-bromoindole-2-carboxylic acid methyl ester derivative are simpler and more convenient, structural modification and preparation are easier, the application range of a substrate is widened, the yield of the product is increased, and the yield of the product is increased. The differentiated requirements on the molecular structure novelty in the field of kinase inhibitors can be met. An epidermal growth factor receptor (EGFR) inhibitor prepared from the 5-bromoindole-2-carboxylic acid methyl ester derivative is higher in inhibition efficiency on biological activity, the physiological solubility is improved more remarkably, a more excellent and stable target binding result can be shown, and the EGFR inhibitor can be used for preparing an epidermal growth factor receptor (EGFR) inhibitor. The application effect of the compound in scenes such as antitumor drug development and the like is favorably improved.

To provide novel methods and uses for increasing a yield of recombinant proteins in host cells, which are simple, efficient and suitable for use in industrial methods.SOLUTION: Provided is a method of increasing a yield of a protein of interest (POI) in an eukaryotic host cell, preferably a yeast, by overexpressing at least one polynucleotide encoding at least one transcription factor of the present invention, preferably Msn4 / 2. Further provided are a recombinant eukaryotic host cell for manufacturing the POI, the host cell being engineered to overexpress at least one polynucleotide encoding at least one transcription factor, as well as the use of the host cell for manufacturing the POI.SELECTED DRAWING: None

The application relates to a cell infiltration inference method and system fusing GO function annotation and PPI network information, and the method comprises the following steps: collecting gene expression data, GO function annotation data and PPI network data; constructing a cell-cell function correlation network and a cell-cell physical interaction network respectively; performing weighted fusion processing on the two networks to obtain a comprehensive cell relationship network; calculating a final cell infiltration score through a restart walk algorithm, and inferring the infiltration degree in a tumor microenvironment according to the final cell infiltration score. The application innovatively fuses GO function annotation information and PPI network data, comprehensively considers the functional similarity and physical or signal interaction between cells, enables the model to understand cell synergy from the biological pathway level and analyze cell direct interaction from the protein interaction level, avoids one-sidedness of a single perspective, and provides a more stereoscopic cognitive framework for tumor microenvironment analysis.

The invention belongs to the technical field of biological medicines, and particularly relates to lipid nanoparticles as well as a preparation method and application thereof. The invention discloses a lipid nanoparticle. The material of the lipid nanoparticle comprises phospholipid and cholesterol. According to the invention, a lipid nano-carrier delivery system entrapped with apoptotic protein Bax is prepared through a microfluidic technology, and high encapsulation rate and stable delivery of protein drugs are realized. The nano-carrier delivery system capable of actively encapsulating the lipidosome realizes targeted delivery to senescent cells in vivo, so that senescent cell apoptosis is effectively induced, the proportion of senescent cells in tissues is reduced, and a new thought and means are provided for anti-aging treatment.

This invention relates to a recombinant type V collagen, its encoding gene, and its applications, belonging to the fields of genetic engineering and protein engineering technology. Based on the amino acid sequence of the α1 chain of human type V collagen, this invention utilizes bioinformatics and other methods to design the amino acid sequence, enabling the recombinant collagen to achieve higher expression efficiency and high stability while maintaining high biological activity. A novel collagen sequence containing 178 amino acids was designed. The nucleotide sequence of this recombinant collagen was optimized using E. coli codon preference to construct a high-expression recombinant strain. The recombinant collagen produced by fermentation of this strain contains no exogenous amino acids such as tags, making it a recombinant humanized type V collagen with good safety. Compared with commercially available type V collagen products, the recombinant type V collagen prepared using the above technical solution has better antioxidant activity and barrier repair capabilities, thus possessing good practical application value.

The invention relates to the technical field of biomedicine detection, and discloses a tumor cell marker detection system for predicting the activation state of intracellular protein kinase. Comprising a marker detection module used for qualitatively detecting epithelial cell markers, mesenchymal cell markers, cell polarity markers and extracellular matrix related markers in tumor cells; the data processing module is used for performing cross validation on an epithelial cell marker, a mesenchymal cell marker, a cell polarity marker and an extracellular matrix related marker; the dynamic weighting module is used for performing dynamic weighting on different markers based on a complex system theory, and endowing epithelial cadherin with a higher weight; and the judgment module is used for determining whether epithelial intercellular substance transformation occurs or not according to the dynamically weighted marker data, and predicting the activation state of intracellular phosphoinositide 3-kinase alpha and the invasiveness of tumor cells based on the determination result of the epithelial intercellular substance transformation.

The application discloses an antibody glycosylation modification regulation method, device and application, relates to the technical field of biopharmaceuticals and protein engineering, and realizes directional regulation of modification types, modification sites and modification proportions of N-glycan and O-glycan of the antibody through three core processes of constructing a glycosyltransferase engineering strain, optimizing a fermentation culture system and precisely regulating modification reaction conditions; solves the technical problems of low modification efficiency, poor specificity and insufficient product uniformity in the existing modification method, can improve the target glycan modification proportion to more than 90%, the modification product purity is greater than or equal to 98%, is suitable for glycosylation modification optimization of therapeutic monoclonal antibodies, bispecific antibodies and antibody drug conjugates, significantly improves the biological activity and pharmacokinetic performance of the antibody, wherein the ADCC activity is improved by 3-5 times, and the CDC activity is improved by 2-4 times, and has the advantages of strong controllability, good adaptability to large-scale production and high cost-effectiveness.

According to the application of the E3 ligase UFL1 modified by the Especially in clearing the SHBs / HBsAg, the SHBs / HBsAg can be cleared by inhibiting the expression of the E3 ligase UFL1 modified by the Especially, so that the effect of treating HBV infection or HBV related diseases is achieved. The strategy of the invention is to directly target and remove the existing SHBs / HBsAg protein, and the action is more direct and rapid. According to the present invention, the inherent protein mass control system (proteasome pathway) of cells is utilized, such that the high biocompatibility and the low off-target toxicity can be provided; and the combination of the strategy and the existing antiviral drugs is expected to further significantly improve the functional cure rate of hepatitis B.

This invention belongs to the field of biomedical engineering technology, providing a method for preparing modular bio-ink for cell spheres and its application in the field of myocardial repair therapy. First, a method for preparing stem cell spheres based on microarrays is described. By introducing a protein / polyphenol composite coating onto the cell spheres, a multifunctional armor is created, providing immune protection and immunomodulatory therapy against the host's immune system to reverse the hostile microenvironment and promote the healing process of infarcted myocardial tissue. Second, using microfluidic droplet control technology, gel microspheres loaded with bioactive substances are prepared from biocompatible biomaterials. These microspheres are then densely packed and coated to form cell sphere particle gels. These gels can be used for disease treatment via direct injection or bio-3D printing, showing promising application prospects.

Provided herein are integrated continuous biomanufacturing processes for producing a therapeutic protein drug substance. Also provided are systems that are capable of continuously producing a therapeutic protein drug substance.

Provided herein are compounds of Formula (II) (e.g., Formula (II-a), (II-b), (II-a1), (II-b1), (II-a2), (II-b2), (II-3), (II-a3), (II-4), (II-a4), (II-5), (II-a5), (II-6), (II-a6), (II-7), (II-a7), (II-7), or (II-a8)), Formula (III) (e.g., Formula (III-1), (III-2), (III-3), (III-4), (III-5), (III-6), (III-7), or (III-8)), Formula (IV) (e.g., Formula (IV-a), (IV-b), (IV-c), (IV-a1), (IV-b1), (IV-a2), (IV-b2), (IV-a3), (IV-b3), (IV-a4), (IV-b4), (IV-a5), (IV-b5), (IV-a6), (IV-b6), (IV-a7), (IV-b7), (IV-a8), or (IV-b8)), Formula (V) (e.g., Formula (V-a) or (V-b), (V-a1), (V-c), (V-d), (V-b1), (V-a2), (V-b2), (V-a3), or (V-b3)), Formula (VI) (e.g., Formula (VI-a), (VI-b), (VI-c), (VI-d), or (VI-e))), or Formula (A) (e.g., Formula (I-a1)), or pharmaceutically acceptable salts thereof, that inhibit a KRas protein (e.g., a dysregulated KRas protein (e.g., a mutated or amplified KRas protein)). This disclosure also provides compositions containing the compounds as provided herein, or pharmaceutically acceptable salts thereof, as well as methods of using and making the same.

To provide a system, apparatus, device and method for an implantable analyte diffusion device.SOLUTION: Embodiments of the present disclosure include, for example, a medical device system including an implantable analyte diffusion device (ADID), the device comprising a cavity, a cell scaffold material (CSM) arranged within the cavity and configured to carry or otherwise retain a plurality of living cells adapted to secrete a therapeutic protein-based drug, and a porous hollow fiber membrane at least partially surrounding the cavity, wherein at least a portion of the membrane is adhered to the CSM by a high durometer adhesive that creates a hemispherical seal at both ends of the membrane. The system also includes a fill port having a dock means at a first end and a micro-diameter tube (MDT) extending from a second end. The MDT is sealed at a distal end to the fill port and at a proximal end to the cavity of the ADID to establish an integral cell fill pathway therein.SELECTED DRAWING: Figure 1

The present disclosure relates to a nucleic acid molecule, a polypeptide, a protein, a cell, or a system comprising a cytokine, optionally a targeting moiety (e.g., a chimeric antigens receptor), and an anchoring structure that can attach to the surface of a cell (e.g., an engineered immune cell), and the methods to prepare the same and to use the same to treat a disease or a condition.

The present invention provides a multiomics approach, which integrate single-cell RNA-sequencing (scRNA-seq) and spatiotemporal transcriptomics (ST) offering potential for dissecting transcriptional networks and revealing cell-cell interactions involved in biomolecular pathomechanisms. The present invention also provides a multimodal approach combining high-throughput scRNA-seq and ST to elucidate XLRS-specific transcriptomic signatures in two XLRS-like models with retinal splitting phenotypes, including genetically engineered (Rs1emR209C) mice and patient-derived retinal organoids harboring the same patient-specific p.R209C mutation. Through multiomics transcriptomic analysis, the endoplasmic reticulum (ER) stress / eIF2 signaling, mTOR pathway, and the regulation of eIF4 and p70S6K pathways as chronically enriched and highly conserved disease pathways between two XLRS-like models are identified. Western blots and proteomics analysis validated the occurrence of unfolded protein responses, chronic eIF2α signaling activation, and chronic ER stress-induced apoptosis. Furthermore, therapeutic targeting of the chronic ER stress / eIF2α pathway activation synergistically enhanced the efficacy of AAV mediated RS1 gene delivery, ultimately improving bipolar cell integrity, postsynaptic transmission, disorganized retinal architecture and electrophysiological responses. Collectively, the complex transcriptomic signatures obtained from Rs1emR209C mice and patient-derived retinal organoids using the multiomics approach provide opportunities to unravel potential therapeutic targets for incurable retinal diseases, such as XLRS.

Discussed herein are novel engineered polypeptides which are effective at cutting and tagging H3 histone tails from endogenous histones, facilitating multiplex "cut-and-paste" middle down proteomics with tandem mass tags. This cut-and-paste proteomics approach permits the quantitative analysis of H3 histone modification crosstalk after treatment with different histone deacetylase inhibitors.

The present invention provides novel markers of the severity of a central nervous system injury, such as spinal cord injury or traumatic brain injury, in a patient. In particular, protein components of inflammasomes in the cerebrospinal fluid that can be used to assess the severity of central nervous system injury in a patient are disclosed. Methods of using such protein biomarkers to determine a prognosis, direct treatment and rehabilitation efforts, and monitor response to treatment for a patient with a central nervous system injury are also described.

This invention relates to the prevention and / or treatment of protein tyrosine kinase-mediated diseases, particularly phosphatidylinositol 3-kinase (PI3Ks)-mediated diseases. PI3Ks are well known as oncological targets, and several PI3K inhibitors have been developed that inhibit numerous class 1A PI3K isoforms. The development of selective inhibitors of PI3K-α may enable sufficient targeted inhibition while avoiding some of the known toxic drawbacks of pan-PI3K inhibitors. The inventors have discovered that a novel carbamoti-oil-pyrrolidine-carboxamide compound of formula (I) exhibits advantageous PI3K inhibitory activity, particularly with high selectivity for the isoform PI3K-α. In particular, this invention relates to the compound of formula (I), or deuterated or tritiated forms of the compound of formula (I), and pharmaceutically acceptable salts thereof. [Formula 1] The present invention also relates to pharmaceutical compositions containing a compound of formula (I) for use in the treatment and / or prevention of protein tyrosine kinase-mediated diseases, and to a compound of formula (I).

The application relates to a cancer driver gene explainable identification method based on trust calibration and prototype learning, and relates to the technical field of biological information identification. A gene graph is constructed by fusing a protein interaction network and gene multi-omics characteristics, and part of nodes are labeled. Label-aware message passing is performed through a trust calibration encoder, the neighborhood is split into a labeled part and a non-labeled part for independent calibration, and node embedding is adaptively fused. An angle margin prototype classifier is used to construct a class prototype on a hypersphere, the decision boundary is expanded, and a prediction result is output. A pivot node self-supervised regularizer is introduced, center nodes are screened from labeled driver genes, positive constraints are applied to neighbor non-labeled nodes, negative penalties are applied to non-neighbors, and a supervised boundary is maintained when non-labeled data is used. Finally, a structured explanation module is used to reuse the internal evidence of the model, a verifiable explanation is provided for prediction, and the unification of high precision and credible explanation is realized.

The invention is applicable to the technical field of immunodetection analysis, and provides a thromboregulatory protein quantitative detection kit and a preparation method thereof.The kit comprises a magnetic bead working solution, a biotin marker working solution, an acridinium ester marker working solution, a thromboregulatory protein calibration product and a thromboregulatory protein control product; the magnetic bead working solution is composed of streptavidin magnetic beads and a magnetic bead diluent, the biotin marker working solution is composed of a biotin-labeled thromboregulatory protein antibody and a biotin diluent, and the acridinium ester marker working solution is composed of an acridinium ester-labeled thromboregulatory protein antibody and an acridinium ester diluent. The thromboregulatory protein quantitative detection kit provided by the invention integrates high sensitivity, high specificity, high precision, strong anti-interference capability, wide linear range and excellent stability, and provides an ideal solution for realizing accurate, rapid and automatic quantitative detection of thromboregulatory protein.

The invention discloses a circRNA (Ribonucleic Acid) and miRNA (Micro Ribonucleic Acid) interaction prediction system and a circRNA and miRNA interaction prediction method of a graph Fourier pulse neural network. The method comprises the following steps: on the basis of high-throughput sequencing omics data of complex diseases, constructing a heterogeneous biological information network containing drugs, diseases, proteins, circRNA, miRNA and lncRNA; converting the topological features of the entities into a unified feature space by using a graph convolutional network; designing a pulse graph neural network in combination with Fourier coding and a pulse neural network, and extracting a topological structure and high-order semantic features in the network; fusing sequences, topologies and semantic features of circRNA and miRNA through a gate multilayer perceptron to obtain embedding features of circRNA and miRNA; and finally, the interaction of circRNA and miRNA is predicted by adopting a Bayesian classifier. According to the method, heterogeneous biological information is modeled from the perspective of network science, Fourier coding, spiking neurons and graph embedding learning are utilized, the action mechanism of circRNA and miRNA in complex diseases can be disclosed, and the method has good practicability and application prospects in the fields of artificial intelligence, life science, clinical medicine and the like.