26 results about "Neuron death" patented technology

The invention belongs to the field of bioinformatics, and relates to an improved integrated deep learning cell communication ligand-receptor interaction prediction method. The method comprises the following steps: firstly, carrying out extraction and dimensionality reduction on biological sequence features of a ligand and a receptor, and constructing multi-modal feature input; secondly, constructing an improved deep neural network branch, introducing a batch normalization layer and a Leaky ReLU activation function, solving the problems of gradient disappearance and neuronal necrosis, and improving regularization strength to prevent overfitting; meanwhile, an enhanced heterogeneous graph auto-encoder branch is constructed, the graph embedding dimension is remarkably expanded to improve the feature capacity, and full convergence of the model is ensured by increasing training rounds; thirdly, fusing the improved deep network with the prediction probability of a heterogeneous graph auto-encoder by adopting a weighted integration strategy; and finally, outputting a potential interaction relationship based on the fusion probability. By optimizing the architecture and the strategy, the prediction accuracy and robustness are remarkably improved, and a reliable tool is provided for analyzing a complex cell communication network.

The present disclosure provides methods and compositions for treating progeria or neurodegenerative diseases, particularly neurodegenerative diseases associated with amyloid deposition and neuronal death, such as Alzheimer's disease. Accordingly, aspects of the present disclosure relate to methods for treating progeria in a subject in need thereof, comprising administering to the subject a TERT-activating therapeutic agent. Other aspects relate to methods for treating a neurodegenerative disease in a subject, comprising administering to the subject a TERT-activating therapeutic agent.

The application belongs to the field of control system design, and discloses a thrust estimation method based on a time domain convolution network, and proposes a thrust estimator based on a multilayer residual time domain convolution network. On the one hand, a Gaussian error linear unit activation function is used to replace the correction linear unit in the residual block to solve the neuron death problem. On the other hand, the overall structure of the multilayer convolution network is adjusted by using residual connection, so that the network training speed and the thrust estimation effect are further improved. The comparison results with the traditional seven methods show that the method has significant advantages in convergence speed and estimation accuracy. In addition, the application also applies the method to an actual control system of an aero-engine, and further verifies the real-time performance and feasibility of the control scheme through a micro turbojet engine test bed test.

This invention relates to the field of pharmaceutical technology for treating diseases related to heavy metal exposure, specifically to the application of a small molecule compound targeting the phosphorylated serine 43 site of ARMC10 in the preparation of drugs for treating neurological damage caused by tin exposure. This technical solution is the first to discover that trimethyltin chloride exposure can specifically induce abnormal phosphorylation of ARMC10, thereby causing neuronal death and cognitive impairment. Based on this mechanism, a small molecule compound targeting a specific phosphorylation site of ARMC10 is proposed, which effectively reverses neurological damage and protects neuronal structure and function by blocking its mediated abnormal mitochondrial division and dysfunction. This solution solves the problem of existing technologies lacking effective treatments for tin exposure-related neurological damage due to the lack of clear drug targets, and has ideal application prospects. This small molecule compound has a well-defined structure and a clear mechanism of action, is easy to further develop, and possesses good drug development and commercialization prospects.

The invention provides application of BC1618 in preparation of a central nervous system protection medicine, and belongs to the technical field of medicine. As a novel drug, the BC1618 inhibits a key component subunit FBXO48 of E3 ubiquitin ligase and further stabilizes SERBP1 so as to play a nerve protection function. The research of the invention shows that the BC1618-FBXO48-SERBP1 axis can promote the survival of retinal ganglion cells and the regeneration of axons after optic nerve injury, and delay the degeneration of axons at the same time. In addition, the nerve protection function of the BC1618 can be further applied to a Parkinson's disease model. Therefore, the BC1618 can be used as a potential medicine composition for preventing or treating and controlling nervous system development disorder related diseases, and can remarkably improve the symptoms such as neuron death, axon loss, neuron dysfunction and dyskinesia caused by central nervous system injury and diseases (such as optic nerve injury and Parkinson's disease).

The invention provides application of auramine O in neuronal death and DNA damage detection and a detection method. Auramine O is an ultrafast fluorescent rotor which is rarely applied to tissue staining, can be specifically combined with an endangered or dead neuron, and shows a spatial and temporal distribution characteristic consistent with Fluro-Jade B staining. The technology is extremely sensitive to desoxyribonuclease pretreatment, which indicates that the binding site of auramine O is mainly located in the damaged neuron DNA molecule, so that auramine O not only can detect neuron death, but also can reflect the damage condition of neuron DNA. According to the technical scheme, operation is fast and simple, and the influence of a sample fixing mode is small; the method can be independently applied to detection of neuron death and can also be combined with other fluorescence detection technologies for application. According to the technology, damaged neurons are disclosed, neuron death detection and neuron death mechanism research are combined together, and an effective means is provided for neuroscience research.

Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of ATXN3 RNA in a cell or animal, and in certain embodiments reducing the amount of ATXN3 protein in a cell or animal. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a neurodegenerative disease. Such symptoms and hallmarks include motor dysfunction, aggregation formation, and neuron death. Such neurodegenerative diseases include spinocerebellar ataxia type 3 (SCA3).

Compositions consist essentially of trigonelline or consist of trigonelline. The compositions can be used in food or beverage applications, pharmaceutical formulations, or as a dietary supplement. The compositions can be administered to a mammal to treat or prevent a mitochondria-related disease or a condition associated with altered mitochondrial function in an individual in need thereof or at risk thereof. The mitochondria-related disease or condition is selected from the group consisting of deleterious effects of aging, stress (e.g., oxidative stress), obesity, overweight, reduced metabolic rate, metabolic syndrome, diabetes mellitus, complications from diabetes, hyperlipidemia, neurodegenerative disease, cognitive disorder, stress-induced or stress-related cognitive dysfunction, mood disorder, anxiety disorder, age-related neuronal death or dysfunction, chronic kidney disease, kidney failure, trauma, infection, cancer, hearing loss, macular degeneration, myopathies and dystrophies, and combinations thereof.

In alternative embodiments, provided are compositions, including products of manufacture and kits, and methods, for reducing addiction to alcohol, and for ameliorating, reversing, treating or preventing Alcoholic Liver Disease (ALD), or alcohol-induced brain injury, wherein optionally the alcohol-induced brain injury comprises neuronal death and astrogliosis (reducing alcohol-induced neuronal death and astrogliosis). In alternative embodiments, provided methods for administering to the individual in need thereof a compound or composition capable of inhibiting or decreasing the expression or activity of an IL-17 or IL-17 receptor (IL-17R) or RORγt protein, transcript and / or gene to treat or for use in: reducing addiction to alcohol; or ameliorating, reversing, treating or preventing Alcoholic Liver Disease (ALD) or alcohol-induced brain injury; or, inhibiting ROR γt to effectively block production of IL-17 cytokines and attenuate development of alcohol-induced liver fibrosis and brain damage.

The invention discloses an application of NORAD in regulation and control of a hypoxic ischemic neuron death mode, and relates to the technical field of biomedicine. Experiments prove that the neuron overexpresses NORAD, so that the cell viability after hypoxia and ischemia is increased, and the mitochondrial DNA copy number is increased, that is, the neuron mitochondrial activity and metabolism can be improved through NORAD overexpression, the neuron cell viability after hypoxia and ischemia is increased, and the method can reduce neuron apoptosis and necrotic apoptosis increase after hypoxia and ischemia.

The present disclosure relates to methods of preventing, or delaying the progression of, death of neurons and / or microgliosis and / or astrogliosis that contributes to the death of neurons. The present disclosure also relates to methods of treating, preventing, or delaying the progression of, a synucleinopathy (e.g., Parkinson's disease). Also disclosed are related in vitro, ex vivo, and in vivo methods of identifying agents and / or compositions useful for preventing, or delaying the progression of, death of neurons and / or microgliosis and / or astrogliosis that contributes to the death of neurons and agents and / or compositions useful for treating, preventing, or delaying the progression of, a synucleinopathy. The agents and / or compositions of the present disclosure decrease the level and / or activity of a cis-regulatory element that propagates the misfolding and aggregation of proteins encoded by synucleinopathy-associated genes in neurons and / or glial cells.

The invention belongs to the technical field of medicines, and particularly discloses an application of IEM-1925 and pharmaceutically acceptable salts thereof in preparation of medicines for treating epileptic status and brain injury caused by nerve toxic agents. In-vivo animal experiments prove that the IEM-1925 is applied after soman poisoning, behavioral epilepsy and electroencephalogram epilepsy can be effectively terminated, neuronal death and neuroinflammation in a hippocampal region can be remarkably relieved, and the long-term cognitive function and anxiety-like behaviors of poisoned living animals can be improved. The curative effect of the medicine is obviously superior to that of the existing standard medicine diazepam in the aspects of epilepsy control, brain injury protection and sequelae improvement. The application range of the IEM-1925 is expanded, the provided medicine is simple in preparation process and low in cost, has good clinical application prospects and market value, provides a brand-new and efficient neuroprotective medicine for treating nerve poison poisoning, and has great medical and public safety value.

The application belongs to the field of neurology and provides a method for detecting neuron death by coupling fluorescence and electron microscopy, comprising the following steps: step one, using Pulsineli's four-vessel occlusion method to make a rat transient global ischemia model, and sampling and processing the model animal to ensure the stability of the sample during the experiment; step two, performing monochromatic fluorescence staining on the sample obtained in step one, then converting the Rhodamine R6 fluorescent label in the slice into 3,3'-diaminobenzidine precipitation, and making the slice into an electron microscopy sample, and determining the experimental results. The application first applies Rhodamine R6 to the field of ultra-morphological detection of neuron death, converts the fluorescent signal of Rhodamine R6 into diaminobenzidine precipitation, thereby realizing the coupling of fluorescence and electron microscopy, and observing the ultra-localization of the positive substance in the dead cells by using an electron microscope.

The invention relates to the field of neuroscience experiments, and discloses a method for increasing the survival rate of brain slice neurons through intrathecal injection of KN93, which comprises the following steps: intrathecal injection: carrying out intrathecal injection of an injection containing KN93 into an experimental animal, the concentration of KN93 in the injection being 5-20 [mu] M; preparing a brain slice: after injection is completed, anesthetizing the experimental animal, cutting the head, taking the brain, cooling the brain tissue, and cutting to form the brain slice; incubating the brain slice: incubating the brain slice in artificial cerebrospinal fluid; and survival rate evaluation: evaluating the neuron survival rate of the brain slice at a preset time point. KN93 directly enters cerebrospinal fluid circulation through intrathecal injection to target calcium / calmodulin dependent protein kinase II in central neurons and block excessive activation of the protein kinase II, so that neuronal death in the brain slice preparation and incubation process is reduced, the survival rate and functional integrity of neurons after long-time incubation are improved, and the brain slice has a good application prospect. And the survival time of brain slice neurons is effectively prolonged.

Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of ATXN3 RNA in a cell or animal, and in certain embodiments reducing the amount of ATXN3 protein in a cell or animal. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a neurodegenerative disease. Such symptoms and hallmarks include motor dysfunction, aggregation formation, and neuron death. Such neurodegenerative diseases include spinocerebellar ataxia type 3(SCA3).

The application provides a kind of vehicle CAN bus anomaly detection method based on lightweight network MobileViT, it is related to network and information security field. By data cleaning and dimension transformation to the original data set, obtain the behavior sample picture data set;An improved lightweight network model MobileViT is constructed and trained to realize the classification of generated behavior sample pictures, so as to convert the vehicle CAN bus anomaly detection problem into a picture classification problem. Use GELU as the activation function of MV2 module in lightweight MobileViT network model, effectively solve the neuron death problem, improve the model convergence speed;In the training process of the model, the learning rate is automatically updated using exponential decay, which prevents the model from falling into local optimum and reduces the training time. The application first applies lightweight network MobileViT to vehicle CAN bus anomaly detection, which can efficiently detect vehicle CAN bus anomalies under the condition of consuming less hardware resources.

A method is provided to increase the expression of the genes CASP3 and THBD; and decrease the expression of the genes COL18A1, CPB2, NPR1, OCLN, BMP2, CLCL6, IL12B, SELPLG, CX3CL1, CASP3, THBD, COL18A1, CPB2, NPR1, CLDN5, CLD3, PIGF, BDNF, CNTF, VEGF-A, CAM-1, PGF, FOX-01, FOX-04, PDGFB, TGFA, HGF, VE-Cadherin, or PLAU. As a result, conditions associated with expression of these genes are treated. Caspase 3 is encoded by CASP3 (GenBank assembly accession: GCA_000001405.22) and cleaves and activates caspases 6 and 7; and the protein itself is processed and activated by caspases 8, 9, and 10. Caspase 3 is the predominant caspase involved in the cleavage of amyloid-beta 4A precursor protein, which is associated with neuronal death in Alzheimer's disease and after spinal cord injury. As caspase 3 is implicated in apoptosis upregulation of CASP3 can be used to induce dysfunction cell removal.

The invention belongs to the technical field of biological medicines, and discloses application of GPNMB in preparation of a medicine for treating hypoxic ischemic brain injury of newborns. The invention develops a new application field. The medicine taking the GPNMB as the raw material can be used for inhibiting neuron death caused by hypoxia and ischemia in the development period of the newborn, and the GPNMB can also be used as an accelerant for activating an AKT signal channel.

The invention discloses fingolimod-modified selenium nanoparticles as well as a preparation method and application thereof, and fingolimod containing amino and hydroxyl is added in the process of preparing the selenium nanoparticles by reducing selenium-containing salt with a reducing agent, so that the fingolimod-modified selenium nanoparticles are obtained. The fingolimod-modified selenium nanoparticles prepared by the invention can be used as a nano-scale drug to carry out intracerebral anti-oxidation and anti-inflammatory treatment in vivo level, alleviate the tau protein phosphorylation process in neurons, inhibit neuronal death, regulate microglial cell polarization in the brain and play a neuroinflammation protection function, and can be used for preparing a drug for treating neuroinflammation. Neuroprotection and selenium nanoparticles are combined, and the treatment effect of the Alzheimer's disease is enhanced through a synergistic mechanism, so that a more effective strategy is possibly provided for treatment of the Alzheimer's disease.

The present invention provides the use of parovatine in the preparation of a medicament for treating acute brain injury following intracerebral hemorrhage. This invention, for the first time, discovers that parovatine can reduce neuronal death and inflammation following intracerebral hemorrhage, improve neurological impairment and cerebral edema in SAH mice, and reduce neurological damage and inflammation in SAH mice. Parovatine has great potential for use in the preparation of medicaments for treating acute brain injury following intracerebral hemorrhage.

The application discloses a kind of polypeptides for treating Parkinson's disease.In the application, it is first found that transient receptor potential M2 type (TRPM2) channel is more expressed in fragile DA neuron subgroup, and its expression amount is positively correlated with age in Parkinson's disease (PD) patient, and the mechanism of action is determined through rigorous experiment, i.e.TRPM2 channel is preferentially activated in ADE neuron through PARP-1 / PARG / ADPR axis, drives Mfn2 / Bcl-2 complex dependent mitochondrial superfusion, causes ADE neuron death.In addition, TRPM2 channel also drives MPTP treatment mouse SNc DA neuron susceptibility through Mfn2 / Bcl-2 mediation.Firstly, it is found that blocking PARP-1 / PARG / ADPR and Mfn2 / Bcl-2 mediated DA neuron death pathway can prevent the death of induced pluripotent stem cell (iPSC) derived DA neuron specific to spontaneous Parkinson's disease (SPD) patient.As susceptible SNc DA neuron loss is the main symptom of PD, therefore, PARP-1 / PARG / ADPR and Mfn2 / Bcl-2 pathway can become a new therapeutic target for PD.

Presented herein are techniques for the determination and use of neural health maps. As used herein, a neural health map refers to a mapping that indicates the neural health of neurons within different regions of a complement of neurons. The neural health indicated in / by the neural health map indicates the ability of a neuron to respond to stimulation. Accordingly, a neural health map can indicate if a particular region of a complement of neurons provides normal response to stimulation, decreased response to stimulation, no response to stimulation (i.e., neuron death), etc.

The present disclosure relates to a pharmaceutical composition for preventing or treating a brain disease, comprising a stem cell-derived exosome surface-modified with a compound capable of binding to dopamine receptors or L-amino acid transporters as an active ingredient. The stem cell-derived exosome according to the present disclosure selectively binds to dopamine receptors (D2) overexpressed as autoreceptors in dopaminergic neurons in the substantia nigra through surface modification. Thereby, local accumulation in dopaminergic neurons is possible. In addition, it was identified that the stem cell-derived exosome exhibited an excellent neuron protective effect and neuron death inhibitory effect. Accordingly, the surface-modified stem cell-derived exosome according to the present disclosure is expected to be usefully used as a composition for preventing or treating a brain disease including Parkinson's disease and Alzheimer's disease.

The invention discloses a rock-soil prediction method based on transfer learning and a lightweight network, and belongs to the technical field of rock-soil engineering, and the method comprises the steps: S1, obtaining soil parameters and boundary conditions of a to-be-predicted geological scene, carrying out the dimensionless processing, and storing all data in a (N, H, W, C) tensor form; s2, constructing a deep learning prediction model, and performing training fine tuning on the model through transfer learning; s3, inputting the input data preprocessed in the step S1 into the deep learning prediction model constructed in the step S2, and obtaining a dimensionless prediction result through forward propagation calculation; s4, performing reverse calculation according to a dimensionless formula to obtain the ultimate bearing capacity or safety coefficient of the actual geological scene; the invention provides a rock and soil prediction method based on transfer learning and a lightweight network, and aims to solve the problems of large training data demand, high computing resource consumption, easy occurrence of neuron death and poor generalization of the existing geological technology prediction model.

The invention relates to the technical field of drugs for treating diseases related to heavy metal exposure, in particular to application of a small molecule compound of a targeted phosphorylated ARMC10 serine 43 site in preparation of drugs for treating nervous system injury caused by tin exposure. According to the technical scheme, it is found for the first time that exposure of trimethyltin chloride can specifically induce abnormal phosphorylation of ARMC10, and then neuronal death and cognitive impairment are caused. On the basis of the mechanism, a small molecule compound targeting a specific phosphorylation site of ARMC10 is provided, and by blocking mitochondrial abnormal division and dysfunction mediated by the small molecule compound, nerve injury is effectively reversed, and the structure and function of neurons are protected. The scheme solves the problem that in the prior art, due to the lack of definite drug targets, no effective therapeutic drug is provided for tin exposure related nervous system injury, and has ideal application prospects. The small molecule compound is clear in structure, clear in action mechanism and easy to carry out subsequent development, and has good druggability and commercialization prospects.

Proposed is a gene-therapy DNA vector, based on gene-therapy DNA vector GDTT1.8NAS12, for treating diseases characterized by progressive pathological changes in the nerve tissue structure and neuron function, including neuron death, which are associated with genetic factors, including mutations in genes coding for proteins critical to the normal functioning of the neurons, inter alia Huntington's disease and hereditary forms of amyotrophic lateral sclerosis, as well as with misfolding of the tertiary structure of proteins, inter alia Parkinson's disease and Alzheimer's disease, damage to the central nervous system, disruption of the oxygen supply to the brain or spinal cord, defective neuronal energy metabolism and axonal transport, or autoimmune demyelinating processes, inter alia multiple sclerosis. As a result of the limited size of the vector part GDTT1.8NAS12, which is not greater than 2600 bp, each of the proposed gene-therapy DNA vectors is capable of effectively penetrating into human and animal cells and expressing the target gene cloned within it.