157 results about "Signal transduction" patented technology

The invention discloses an antibody combined with interleukin 4 receptor (IL-4R) protein and a computer optimization method, a compound structure analysis method and application thereof, the antibody comprises a Fa-2 sequence, a Fa-3 sequence, a Fa-4 sequence, a Fa-5 sequence, a Fa-7 sequence, a Fa-13 sequence, a Fa-15 sequence, a Fa-16 sequence, a Fa-17 sequence, a Fa-19 sequence and a Fa-23 sequence, and the Fa-2 sequence, the Fa-3 sequence, the Fa-4 sequence, the Fa-5 sequence, the Fa-7 sequence, the Fa-13 sequence, the Fa-15 sequence, the Fa-16 sequence, the Fa-17 sequence, the Fa-19 sequence and the Fa-23 sequence comprise a heavy chain variable region and a light chain variable region. The amino acid sequences of the amino acid sequences are respectively shown as SEQ ID NO: 7, 8, 9, 10, 11, 12, 13, 14, 17, 18, 29, 30, 33, 34, 35, 36, 37, 38, 41, 42, 49 and 50. According to the invention, a brand-new IL-4R epitope is found, and an antibody with a'non-ligand blocking 'characteristic is obtained for the first time. The invention opens up a brand new path for developing a therapy for intervening the IL-4R pathway through a new mechanism of regulating signal transduction or interacting with other coreceptors and the like, and is expected to overcome the limitation of the existing therapy. According to the method, computational biology and experimental structure biology are seamlessly connected, a set of repeatable and efficient research and development process is formed, and the method has a wide application prospect.

The invention discloses long-acting high-dynamic hydrazone bond hydrogel as well as a preparation method and application thereof, and particularly relates to the technical field of biomedical materials. The preparation method comprises the following steps: taking 1-adamantane acetic acid and adipic dihydrazide modified sodium hyaluronate and benzaldehyde-terminated eight-arm polyethylene glycol as carrier raw materials; the hydrazone bond hydrogel with relatively high stability is prepared through a coupling reaction of an aldehyde group of benzaldehyde-terminated eight-arm polyethylene glycol and a hydrazide group of 1-adamantane acetic acid and adipic dihydrazide modified sodium hyaluronate. The beta-cyclodextrin modified m-phenylenediamine catalyst is dynamically combined into the carrier through reversible host-guest complexation between beta-cyclodextrin and 1-adamantane acetic acid, so that the long-acting high-dynamic hydrazone bond hydrogel is obtained, and the requirement of three-dimensional culture of stem cells on mechanical properties can be met; and network dynamics can be maintained for a long time, so that stem cell spreading is supported, mechanical signal transduction is activated, osteogenesis-related gene expression is promoted, and stem cell osteogenesis differentiation capability is enhanced.

The invention belongs to the technical field of biology, and particularly relates to application of baicalin to preparation of a medicine for treating preeclampsia by inhibiting trophoblast ferroptosis induced by NETs. The baicalin inhibits downstream signal transduction by specifically interfering a key activation step of PKC [beta] 2 and a membrane translocation process coupled with a second signal, and finally plays a role in inhibiting ferroptosis of trophoblasts. The discovery provides a brand new perspective for understanding the molecular action mechanism of the medicine. According to the application, baicalin influences ferroptosis induced by NETs in trophoblast cells by inhibiting membrane translocation and activation of PKC beta2, so that the biological function of baicalin is exerted. The discovery of the mechanism further deepens the important significance of people on NETs and baicalin in disease induction and treatment, and a thought is provided for research and development of a new treatment scheme for preeclampsia.

The invention provides a chimeric antigen receptor for regulating and controlling a signal time sequence and application of the chimeric antigen receptor. The chimeric antigen receptor sequentially comprises a signal peptide, an extracellular domain, a transmembrane domain and an intracellular domain from an N terminal to a C terminal, the extracellular structural domain comprises an antigen recognition region and a hinge region; the intracellular domain comprises a costimulatory signal transduction region and a CD3 [zeta] intracellular region variant; the CD3 [zeta] intracellular region variant comprises three ITAMs, and the arrangement sequence of the ITAMs is ITAM3-ITAM2-ITAM1 from the N end to the C end. Compared with a conventional chimeric antigen receptor containing a wild CD3 zeta intracellular region, the chimeric antigen receptor provided by the invention can significantly enhance the functional activity of immune cells expressing the chimeric antigen receptor, which is specifically embodied in stronger multiplication capacity and durability, and significantly improves the antigen sensitivity and targeted killing efficacy.

This invention belongs to the field of biomedical technology, specifically relating to the application of DNA damage response gene-related SNPs in the treatment and prognosis of acute myeloid leukemia (AML). This invention is the first to discover that single nucleotide polymorphisms (SNPs) in the DNA damage response pathway (focusing on three major functional modules: damage sensing, signal transduction, and DNA repair) are closely related to the clinical characteristics, treatment response, and survival prognosis of AML. This lays the foundation for constructing a multi-gene risk model based on the DNA damage response pathway and provides theoretical support for integrating germline SNP maps into precision medicine strategies for AML.

The invention discloses a detection kit based on orthogonal dual-channel label-free CRISPR-Cas and application of the detection kit, relates to the technical field of nucleic acid detection, and constructs an orthogonal dual-channel response system by utilizing the differentiated cleavage activity of Cas12a targeted DNA and Cas13 targeted RNA to a substrate. A Cas12a pathway is reported by utilizing protoporphyrin IX to be compounded with G-quadruplex G4DNA, and a Cas13a pathway is reported by utilizing DFHBI to be compounded with a Broccoli RNA structure, so that label-free signal transduction is realized. Through accurate screening of fluorophores, channel specificity is ensured, and optical signal crosstalk is eliminated. Mycobacterium tuberculosis (MTB) and respiratory syncytial virus (RSV) are used as model pathogens for verification, and a multiple recombinase polymerase amplification (RPA) technology is combined, so that the detection sensitivity on a synthetic target reaches a single molecule level. The system has high specificity, and even if the concentration of a non-target pathogen is increased by 100 times, no cross reaction exists.

The present application relates to a kind of based on logic gate double-target point chimeric antigen receptor modified TIL cell, lentivirus expression vector and application, belong to tumor immunotherapy and gene editing technical field.The TIL cell based on logic gate double-target point chimeric antigen receptor modified in the application, double-target point chimeric antigen receptor includes chimeric antigen receptor EGFR and chimeric antigen receptor GD2;Chimeric antigen receptor EGFR is composed of CD8 alpha signal peptide, anti-EGFR single-chain antibody, CD8 alpha transmembrane region, 4-1BB costimulatory domain and CD3 zeta intracellular signal domain in series;Chimeric antigen receptor GD2 is composed of CD8 alpha signal peptide, anti-GD2 single-chain antibody, CD28 transmembrane region, CD27 costimulatory domain and CD3 zeta intracellular signal domain in series.The present application solves the defects that lentivirus transduction targeting is poor in prior art, CAR signal activation specificity is insufficient, TIL cell is easily exhausted, has the advantages that gene integration is accurate, signal transduction is controllable, in-vivo survival time is long, can be efficiently used for the immunotherapy of double-antigen co-expression solid tumor.

The present application belongs to the technical field of fruit fly prevention and control, and discloses a disorienting agent, a preparation method and application thereof. The disorienting agent contains rosemary extract and orange peel essential oil. The rosemary extract and orange peel essential oil contain terpenes and other compounds (such as 1,8-cineole in rosemary), which can compete with natural signal molecules to bind to odor binding proteins or olfactory receptors, which can cause fruit flies to fail to activate the correct nerve signal or directly block the signal transduction pathway. The orange peel essential oil in the disorienting agent has a strong smell, which can strongly cover or mask the weak smell signal emitted by the fruit, forming an "olfactory masking" effect, so that the fruit fly cannot find the fruit. Moreover, compared with sex pheromones as disorienting agents, which can only act on male fruit flies, the disorienting agent of the present application can interfere with the olfactory receptors of adult fruit flies to make them unable to find the target, so that they cannot accurately locate the oviposition site and harm the fruit. The disorienting agent is effective for both female and male fruit flies.

The invention discloses a method for improving rooting quality of eucommia ulmoides by regulating ethylene, and relates to the technical field of eucommia ulmoides breeding. The method comprises the following steps: selecting eucommia ulmoides tissue culture clonal elongation buds as a material; inoculating the elongated buds into an adventitious root one-step induction (O treatment) culture medium; in addition, performing two-step rooting induction (T treatment) on the elongated buds: pre-culturing for 7 days, and then transferring into a hormone-free culture medium; differential genes of an ethylene signal transduction pathway and a biosynthesis pathway on the twelfth day and the twenty-first day of O treatment and T treatment are analyzed, and it is determined that ethylene may be a main factor affecting the two rooting modes; the mutual regulation effect of NAA and ethylene is further verified, and the development of adventitious roots of eucommia ulmoides is regulated by indirectly regulating the generation of ethylene. The method has the beneficial effects that the efficient eucommia ulmoides rooting method which is high in rooting efficiency, robust in root system, few in callus formation and clear in mechanism is developed, and the method has important significance in research on promoting adventitious root development of eucommia ulmoides.

The invention relates to the field of information systems and cloud platforms for interaction detection of proteins and metabolites and health correlation in biological material test and analysis, and discloses a short figure development multi-dimensional data fusion evaluation system based on an intestinal brain liver axis quantitative model. Comprising a data acquisition module, an axial gating mapping module and a growth steady state evaluation module, and the data acquisition module acquires an intestinal metabolism component, a liver growth axis component and a neuroendocrine component of a subject; the axial gating mapping module is used for determining signal transduction time delay, calling an intestinal metabolism component at the T-tau moment as a parameter reference through asynchronous offset processing, and determining a gating calibration coefficient in combination with a neuroendocrine component fluctuation slope; and the growth steady state evaluation module performs gain compensation on the liver growth axis component according to the calibration coefficient and outputs a growth and development evaluation index. According to the invention, asynchronous interference of biochemical signal circulation is solved, evaluation model drift caused by phase dislocation is eliminated, and the accuracy of development blocking reason screening is enhanced.

Provided are a set of fully human TSH receptor (TSHR)-blocking monoclonal antibodies targeting a CHK36 homolog cluster, a preparation method therefor, and an application thereof. The method comprises the following steps: using flow cytometry to sort plasma cells and single memory B cells that specifically recognize TSHR in peripheral blood of a patient with a high titer of TSH-blocking antibodies (TBAb), performing in vitro cloning of antibody light and heavy chains and performing recombinant expression, and using hTSHR-CHO cells to perform screening and validation of antibody properties to obtain a blocking monoclonal antibody that specifically targets human TSHR. The fully human TSH receptor-blocking monoclonal antibodies specifically bind to a TSHR, and effectively block signal transduction after a TSH binds to a receptor, inhibit the synthetic secretion of thyroid hormones, and significantly reduce and inhibit TSHR expression and fibrosis in orbital fibroblasts of effector cells associated with thyroid-related ocular diseases. The fully human TSH receptor-blocking monoclonal antibodies have broad application prospects in the treatment of Graves' disease (GD) and other diseases caused by hyperthyroidism, such as thyroid eye disease (TED).

The present disclosure provides compositions and methods for inducing protein-protein heterodimerization in the presence of salicylic acid or a synthetic derivative thereof, useful for modulating signal transduction, protein activation, and gene expression in response to chemical stimuli.

The invention discloses a composite exosome encapsulating linear macromolecular nanoparticles as well as a preparation method and application thereof, and belongs to the technical field of biological materials and regenerative medicine. Aiming at the pain points that in the prior art, when linear macromolecules such as collagen and hyaluronic acid are encapsulated by exosomes, the encapsulation efficiency is low, the structure of the exosomes is easy to damage, and the molecular weight adaptability is poor, the invention provides the preparation method which comprises the following steps: firstly, pretreating the collagen of 5 kDa to 330 kDa and the hyaluronic acid of 10 kDa to 2200 kDa into dense nanoparticles of 10 to 150 nm and PDI less than or equal to 0.15 through a nanoprecipitation method, an electrostatic complexation method and the like; and encapsulating in the exosome through an electroporation method, a freeze-thaw cycle method or an ultrasonic method, and purifying to obtain the composite exosome. According to the method, linear macromolecules with different molecular weights are adapted by flexibly adjusting process parameters, the encapsulation efficiency is remarkably improved, and the membrane structure of the exosome can be kept complete. The obtained composite exosome has the signal transduction function of the exosome and the biological activity of linear macromolecules, and generates a synergistic effect in tissue repair.

The invention discloses application of a tomato gene SlZFP2 as a negative regulation factor in regulation of plant cold resistance, belongs to the technical field of plant genetic engineering, and finds and confirms that the tomato zinc finger protein gene SlZFP2 is a key negative regulation factor of plant cold resistance for the first time. Experiments show that the expression of the SlZFP2 is induced by low temperature, the overexpressed transgenic tomato plant shows more serious cold injury symptoms under low temperature stress, the photosynthetic efficiency is reduced, active oxygen (H2O2 and O2-) is excessively accumulated, and the activity of antioxidant enzymes (SOD, POD and CAT) is weakened; the overexpression of the SlZFP2 can inhibit the biosynthesis and signal transduction of abscisic acid (ABA), and down-regulate the expression of cold response genes SlGRAS4 and SlCBF1; based on the discovery, the invention provides an application of using the SlZFP2 gene or an expression product thereof as a molecular marker for screening tomato materials with different cold resistance, creating a transgenic plant with reduced cold resistance by overexpressing the SlZFP2, and providing a recombinant DNA construct containing an SlZFP2 coding sequence and a host cell.

The present disclosure relates to compounds and methods useful for the modulation of signal transducer and activator of transcription 6 ("STAT6") via ubiquitination and / or degradation by compounds according to the present disclosure. The present disclosure also provides pharmaceutically acceptable compositions thereof and methods of using said compositions in the treatment of various disorders.

This invention relates to the field of congenital heart disease treatment technology, and discloses the application of sapropterin in the prevention and treatment of bisphenol fluorene-induced congenital heart disease in fetuses. The congenital heart disease includes cardiac structural defects, heart failure, or cardiomyocyte lesions, specifically selected from ventricular septal defects, atrial septal defects, tetralogy of Fallot, myocardial hypertrophy, decreased cardiac ejection fraction, decreased short-axis contraction rate, cardiomyocyte ferroptosis, myocardial tissue inflammatory infiltration, or myocardial collagen fibrosis. Sapropterin is used as a direct supplement to biological tetrahydropterin (BH4). Through exogenous intervention, it precisely reverses the endogenous BH4 deficiency caused by bisphenol fluorene exposure, restores the expression of GTP cyclase 1 (GCH1) and the dynamic balance of RNA m6A, and upregulates the level of YTH domain family protein 2 (YTHDF2), thereby blocking ferroptosis signal transduction, reducing oxidative stress and inflammatory response, and inhibiting the process of myocardial tissue fibrosis at the molecular level.

The present application relates to tetrahydroprotoberberine THPB derivatives, and particularly relates to application of a tetrahydroprotoberberine THPB derivative GP10 in preparation of a medicine for improving or treating epilepsy and neuroinflammation; the new candidate compound GP10 discovered by the present application has significant anti-epilepsy activity, not only expands the pharmacological effect spectrum of THPBs, but also provides a new strategy for research and development of anti-epilepsy drugs or auxiliary treatment drugs. Meanwhile, the present application research proves that GP10 can interfere with the structure of DAMP molecules, affect the combination of DAMP molecules and PRR and the downstream signal transduction, and the mechanism is verified through in-vivo and in-vitro experiments, which provides a new theoretical basis and thought for development of anti-inflammatory drugs.

The present disclosure provides compounds of Formula (Vc) and pharmaceutically acceptable salts thereof, and methods of using the same. The compounds and methods have a range of uses as therapeutic, diagnostic and research tools. In particular, the subject compositions and methods are used to reduce signal transduction output of oncogenic proteins.

1. The name of the design product: multifunctional enzyme label instrument. 2. The use of the design product: for nucleic acid, protein concentration, enzyme activity analysis and other conventional molecular detection; signal transduction research, cell signal event active oxygen, modification detection; cell viability, apoptosis, killing and other overall level analysis. 3. The design points of the design product: in shape. 4. The picture or photo that best indicates the design points: perspective drawing.

The present disclosure provides compounds and pharmaceutically acceptable salts thereof, and methods of using the same. The compounds and methods have a range of uses as therapeutic, diagnostic and research tools. In particular, the subject compositions and methods are used to reduce signal transduction output of oncogenic proteins.

Modulators of signal transducer and activator of transcription 6 (STAT6) are provided, including compounds of Formula I, la, lb, Ic, Id, II, Ila, lib, and lie, pharmaceutical compositions thereof, and methods of treating an inflammatory condition or disease.

The invention discloses application of 2-fluorofucose in preparation of a medicine for relieving acute kidney injury, and belongs to the technical field of biology. In-vitro cell experiments and animal experiments prove that 2-fluorofucose can inhibit core fucosylation, competitively inhibit the activity of fucosyltransferase, down-regulate the expression of FUT8 and reduce the core fucosylation level in kidney tissues and renal tubular epithelial cells; by inhibiting core fucosylation, effectively reversing EMT phenotypic transformation induced by hypoxia reoxygenation or ischemia reperfusion, up-regulating E-cadherin expression, down-regulating alpha-SMA and Snail expression and reducing cell migration ability, phosphorylation activation of an ERK pathway is remarkably inhibited, and downstream inflammatory factor release and cell injury signal transduction are blocked, so that the ERK pathway can be used for inhibiting ERK pathway phosphorylation activation. The invention provides application of 2-fluorofucose to preparation of a medicine for relieving acute kidney injury. The invention provides a new choice for treating acute kidney injury, has the outstanding advantages of remarkable curative effect, high safety and the like, and has a wide application prospect.

The invention provides a mammal protein efficient expression system based on a prokaryotic two-component signal transduction system (TCS, two-component system) and application of the mammal protein efficient expression system, and the mammal protein efficient expression system comprises the TCS capable of efficiently recruiting transcription factors and a carrier capable of being induced by the TCS to express a target gene. By transfecting mammalian cells with the system, a protein of interest can be produced in the cells or extracellular proteins can be produced in a secreted form. Based on the mammal protein high-efficiency expression system provided by the invention, stable and high-level expression of the target protein can be realized. The invention provides a new method for production of therapeutic proteins and antibodies, provides key technical support for preparation of mammalian protein samples in the research fields of structural biology and the like, and has important scientific significance for development of life science, diagnosis and treatment of diseases and research and development of medicines.

The invention is applicable to the technical field of molecular biology and biology, and provides a corn protein phosphatase gene ZmPRH20 and application thereof, the sequence of genome DNA of the corn protein phosphatase gene ZmPRH20 is shown as SEQ ID NO: 1, the sequence of cDNA of the corn protein phosphatase gene ZmPRH20 is shown as SEQ ID NO: 2, and the sequence of CDS of the corn protein phosphatase gene ZmPRH20 is shown as SEQ ID NO: 3. The invention provides a protein phosphatase ZmPRH20 gene related to corn drought stress, the protein phosphatase ZmPRH20 gene can positively regulate the drought resistance of a plant, the drought resistance survival rate is remarkably improved compared with that of a wild type after overexpression in arabidopsis thaliana, and the ZmPRH20 protein coded by the gene participates in ABA signal transduction and regulates stress response gene expression through interaction with ABA receptor protein.

The invention discloses application of isorhamnetin in preparation of antiarrhythmic drugs, and belongs to the technical field of medicines. The isorhamnetin is proposed for the first time to effectively improve myocardial conduction rate increase, conduction discrete index increase and heart rate acceleration symptoms of tachyarrhythmia patients, and the medical application of the isorhamnetin is expanded. The isorhamnetin serving as the anti-arrhythmia drug has a very good inhibition effect on increase of cAMP / PKA signal transduction pathways, realizes reversal of occurrence of arrhythmia and has important guiding significance in treatment of arrhythmia. The isorhamnetin is used as the active ingredient of the anti-arrhythmia medicine, the safety is high, the side effect is small, a new way is provided for development of the anti-arrhythmia medicine, and the application blank of the isorhamnetin in the field is filled.

This invention belongs to the field of biomedical technology and discloses the application of NP in the preparation of a glycemic regulator for aging type 2 diabetes. The NP is a nanoscale complex formed by hydrogen bonding of turtle egg peptide with a molecular weight less than 3 kDa and naringenin at a mass ratio of 100:1. The formulation promotes liver glycogen synthesis and repairs pancreatic tissue structure and pancreatic β-cell function by activating the hepatic IRS1 / PI3K / AKT / GSK-3β signaling pathway and upregulating GLUT2 protein expression. The NP provided by this invention can significantly reduce fasting blood glucose levels in aging type 2 diabetic mice, improve oral glucose tolerance, and reduce the area under the blood glucose curve. Simultaneously, by restoring insulin signal transduction, it significantly reduces the insulin resistance index and improves the insulin sensitivity index, with an improvement level approaching that of the classic hypoglycemic drug metformin.

The application discloses a memristor, a method for preparing the same and an artificial synapse device, and the memristor comprises a glass cone and a polyelectrolyte structure on the inner wall of the glass cone; the glass cone has a first end opening and a second end opening arranged oppositely, the diameter of the first end opening is smaller than that of the second end opening, and the polyelectrolyte structure is located on the inner wall of the first end opening. Thus, the memristor has low power consumption of a picojoule level, a low working potential and high efficiency. When a pulse potential stimulus is applied, the memristor can generate a double-pulse facilitation and a double-pulse inhibition effect similar to a neuron synapse, and due to the existence of an ion effect, the effective regulation of the plasticity of the system can be realized. Further, the signal transduction function based on ions can be realized by being combined with a micro-injection system. In addition, the memristor has excellent stability and designability and the like.

The present disclosure relates to engineered polypeptides comprising a molecular component of IL-10 capable of modulating signal transduction associated with IL-10 and methods of use thereof. In some aspects, the polypeptides of the present disclosure exhibit cell type bias activity. In some aspects, the polypeptides of the present disclosure substantially retain the anti-inflammatory properties of IL-10, but significantly reduce the pro-inflammatory properties of IL-10. The present disclosure provides methods of use of engineered polypeptides in the treatment of disease.

The invention belongs to the technical field of electrochemical biosensing, and particularly relates to a membrane-free anti-interference metabolite detection device and a construction method thereof, in particular to a membrane-free anti-interference biosensor based on hydrogen peroxide signal transduction and a construction method thereof. The sensor comprises a working electrode and a reaction layer arranged on the surface of the working electrode, wherein the reaction layer comprises a biological recognition unit for in-situ generation of hydrogen peroxide and a catalysis unit for electrochemical reduction of hydrogen peroxide; the catalytic unit comprises a nitrogen-doped carbon matrix on which at least one of iron (Fe), cobalt (Co) and copper (Cu) in a monatomic form and molybdenum carbide (MoC) nanoparticles are loaded. The sensor disclosed by the invention shows excellent anti-interference capability and detection accuracy in a real human body sample, and can be expanded and applied to various oxidase coupled metabolite detection systems which are generated by depending on hydrogen peroxide, so that a universal sensing platform is provided for non-invasive or minimally invasive metabolite analysis in complex biological fluid.

Provided herein are FLT1 binding proteins, as well as related nucleic acids, vectors, host cells, pharmaceutical compositions and kits. The present disclosure additionally provides methods of treating a subject in need thereof, including subjects in need of treatment for PAD, CLI, ANOCA, or heart failure (HF). Further provided are methods of increasing VEGF-mediated and / or PlGF-mediated signal transduction in a subject, which, in turn, increases blood flow, capillary density, capillary or coronary growth, and / or cardiac perfusion in the subject. The present disclosure further provides methods of reducing blood pressure and risk of heart failure in a subject. In exemplary embodiments, each of the methods comprise administering to the subject a pharmaceutical composition of the present disclosure. In various embodiments, the pharmaceutical composition comprises a FLT1 binding protein of the present disclosure.