3197 results about "In vivo" patented technology

The invention relates to application of a targeted inhibition circPDK1 reagent in preparation of an anti-esophageal cancer drug, and belongs to the field of biological medicines. The reagent for targeted inhibition of circPDK1 expression provided by the invention is shRNA or siRNA, and in-vivo and in-vitro experiments prove that the reagent can significantly inhibit circPDK1 expression and inhibit growth and migration of esophageal cancer tumor cells; after siRNA of targeted annular circPDK1 is packaged into efficient and low-toxicity LNP-siRNA, circPDK1 expression is specifically silenced, proliferation and migration of esophageal cancer tumors can be remarkably inhibited, and a basis is provided for clinical treatment and scientific research of esophageal cancer related circRNA.

The invention provides a PET tracer precursor compound as well as a preparation method and application thereof, and also discloses a < 68 > Ga-labeled PET tracer, the PET tracer precursor compound is simple in preparation method, short in preparation time and high in radiochemical yield, and has the advantages of good in-vivo and in-vitro stability, high specificity, high intake and the like; the tumor or inflammation part can be accurately and stably detected and positioned; the Ga-68 labeled targeted PARP-1 radioactive probe synthesized on the basis of the compound Olaparib can realize qualitative diagnosis of PARP-1 in tumors, further realizes non-invasive accurate quantification of PARP-1 in tumors, provides a reliable basis in stages of clinical staging, treatment decision, curative effect monitoring and the like, and finally realizes accurate diagnosis and treatment.

The invention provides a method and system for predicting the utilization rate of feed amino acid in multiple stages of laying hens, and relates to the field of bioinformatics, and the method comprises the following steps: obtaining chemical component measured values of feed raw material samples in different growth stages of the laying hens and in-vivo measured values of standard ileum amino acid digestibility; performing predictive factor screening according to the chemical component measured value and the standard ileum amino acid digestibility in-vivo measured value to obtain a predictive factor combination; constructing a prediction model according to the prediction factor combination to obtain a candidate prediction equation; optimizing according to the candidate prediction equation, and screening to obtain an optimized equation; performing model verification according to the optimization equation to obtain a target prediction model; and performing digestibility prediction according to the target prediction model to obtain a predicted standard ileum amino acid digestibility value. According to the method, the standard ileum amino acid digestibility is accurately predicted based on in-vitro detection data, and the limitation of a traditional in-vivo determination method is effectively overcome.

The invention relates to novel compositions and methods of using maribavir which enhance its effectiveness in medical therapy, as well as to maribavir isomers and methods of use thereof for counteracting the potentially adverse effects of maribavir isomerization in vivo in the event it occurs.

A method of treating or inhibiting a viral infection in a human subject, such as a SARS-CoV-2 infection, involves inhibiting in vivo the expression or activity of one or a combination of the subject's genes required for viral infection. Single genes or subsets of genes for inhibition of activity or expression are selected from certain identified genes. Methods of administration of certain known small molecules or other therapeutics which mimic loss of function of the identified genes are provided. Similar methods for conducting screens of host genes required for viral infection are shown.

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

The invention discloses a two-dimensional bionic nanostructure assembled based on receptor-ligand acting force and a preparation method of the two-dimensional bionic nanostructure. The core characteristic of the two-dimensional bionic nanostructure is that the ultrafine particles modified by ligand molecules are anchored on the surface of a cell membrane fragment with a corresponding receptor expressed on the surface through a receptor-ligand effect, so that uniform compounding of the ultrafine particles and the cell membrane is realized; the bottlenecks of low compounding efficiency, functional site masking and the like caused by high surface curvature of small-size particles in the traditional cell membrane complete wrapping technology are broken through. According to the preparation method disclosed by the invention, the binding force between the cell membrane and the ultramicro particles is stronger, the off-target phenomenon of the ultramicro particles in the in-vivo circulation process can be avoided, the response release of the ultramicro particles under the competition effect in a lesion region expressed by a high-abundance receptor can be realized, and the preparation method has a good application prospect in the aspect of precise drug delivery. Meanwhile, the in-vivo circulation time of the ultrafine particles is prolonged by membrane loading, the biocompatibility of the ultrafine particles is improved, and the effectiveness and low toxicity of a drug delivery system are ensured.

The invention relates to a curcumin-loaded MMP response type melittin nano-pellicle vesicle as well as a preparation method and application thereof, and belongs to the technical field of pharmaceutical preparations. The preparation method comprises the following steps: firstly, preparing curcumin entrapped lipidosome; then carrying out culture amplification on engineering bacteria carrying melittin recombinant plasmids, extracting cell membranes after removing cell walls, and carrying out ultrasonic treatment and membrane extrusion to obtain melittin cell membrane nano-vesicles; fusing the curcumin lipidosome and the cell membrane nano-vesicles in an ultrasonic extrusion mode to obtain fused vesicles; and finally, carrying out surface calcium phosphate mineralization treatment on the fused vesicles to obtain the curcumin-loaded MMP response type melittin nano pellicle vesicles. The nano mycofilm vesicle prepared by the invention can be used for preparing antitumor drugs, and the biocompatibility and in-vivo stability of nanoparticles are improved by introducing a calcium phosphate coating; through combined delivery of melittin and curcumin, the anti-tumor effect is enhanced, so that the growth and proliferation of tumor cells are inhibited.

The present application relates to a virus of reverse genetic operation construction of NADC34-like PRRSV2. Specifically, the full gene sequence of NADC34-like PRRSV2 BJ1805-2 isolated strain is segmented and connected to the vector by using PCR amplification, enzyme digestion and other methods with pACY177 plasmid as the carrier, and the BJ1805-2 full-length infectious clone recombinant plasmid (rBJ1805-2) is obtained. The infectious clone virus rBJ1805-2 is rescued in vitro, and the first NADC34-like PRRSV2 strain infectious clone platform in China is successfully built. The present application also relates to a modification method for constructing NADC34-like PRRSV2 strain which can adapt to Marc-145 cell passage culture. The infectious clone virus constructed by the present application has good in vitro and in vivo proliferation efficiency, and can cause specific viremia after inoculation in pigs; it has good safety, does not cause fever after inoculation in pigs, and will not cause piglet death. The modified strain can be used as a candidate strain for developing the first NADC34-like PRRSV2 specific vaccine in China, and is conducive to the prevention and control of PRRSV epidemic in China.

The invention provides a mutant of enterovirus 71 and virus-like particles thereof, and relates to the field of biological medicines. The enterovirus 71 type virus-like particle is obtained by modifying structural genes VP0, VP1 and VP3 of virus capsid protein by utilizing computational structure biology and completing self-assembly in vivo through a hansenula polymorpha expression system. Compared with the unmodified enterovirus 71 type mutant and the virus-like particles thereof, the enterovirus 71 type mutant and the virus-like particles thereof have the advantages that the immunogenicity can be obviously improved, and the clinical application prospect is relatively high.

According to the invention, the multi-mode time-frequency domain conversion and the deep learning technology are combined, and a multi-component mixed Raman spectrum unmixing method is developed, so that clinical in-vivo and in-situ detection and disease diagnosis of novel Raman probes, instruments and the like are facilitated. The method comprises the following steps: (1) converting a mixed Raman spectrum from a time domain to a frequency domain by using fast Fourier transform (FFT), discrete cosine transform (DCT) and discrete sine transform (DST), and extracting frequency domain features; (2) extracting multi-scale local time-frequency domain characteristics of the mixed spectrum by using short-time Fourier transform (STFT) and discrete wavelet transform (DWT); (3) carrying out spectral unmixing calculation in each mode in combination with a one-dimensional attention mechanism U-shaped neural network model; and (4) fusing various modal unmixing results by using a meta-learning method, and analyzing the weight of each modal to obtain an accurate unmixing spectrum. Compared with a traditional Raman spectrum analysis method, the Raman spectrum multi-component signal unmixing method based on multi-modal time-frequency domain transformation and deep learning can accurately separate independent Raman signals of different tissue structures and biochemical components in a complex environment in a living body, so that the unmixing accuracy of the Raman spectrum multi-component signal is improved. Therefore, convenience is provided for subsequent disease mechanism analysis and diagnosis. The method provides an innovative and potential solution for in-vivo and in-situ detection analysis and disease diagnosis of medical clinical Raman spectroscopy.

The invention discloses a multi-modal imaging system and method for a small animal living body. The system comprises a multi-modal fusion imaging module which is responsible for multi-modal image acquisition and primary processing; the real-time dynamic monitoring module is used for capturing bioluminescence / fluorescence signals in real time through a photon counting detector, receiving optical, nuclear medicine and magnetic resonance data, correcting motion artifacts based on a multi-scale space-time registration engine and adjusting scanning parameters through a real-time pharmacokinetic-physiological feedback mechanism; the low-radiation and biological compatible module is used for automatically optimizing the dosage of a tracer agent according to the weight of the animal, the scanning part and historical data by using a dosage prediction model; and the multi-modal data fusion module is used for performing non-rigid registration of multi-modal images based on a Transform cross-modal registration network, constructing a multi-species pharmacokinetic knowledge graph by utilizing multi-species metabolism chip data, integrating mouse, dog, primate and humanized liver chip data, and mining a cross-species metabolism rule through a graph neural network.

The present disclosure provides Crispr / cas9-based repressors for silencing gene targets in vivo and methods of use.

The present application relates to an antibody capable of specifically binding to c-Met or antigen-binding fragment thereof, and an immunoconjugate, a pharmaceutical composition and a multispecific molecule comprising the same. The present application further relates to the use of the antibody specifically binding to c-Met or an antigen-binding fragment thereof and the multispecific molecule. Compared with the control antibody, the bispecific antibody or defucosylated bispecific antibody of the present application can block HGF-dependent TKI resistance; block the proliferation and migration of tumor cells induced by HGF, induce ADCC effect, and inhibit tumor growth in vivo.

The invention relates to the field of tumor cell therapy, in particular to application of T lymphocyte chimeric with a B7-H3 receptor to treatment of head and neck tumors, and provides an anti-B7-H3 scFv, the scFv comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises an HCDR region and an HFR region, and the light chain variable region comprises an LCDR region and an LFR region; compared with a wild type scFv sequence, the scFv sequence has the advantage that a plurality of amino acids with positive charges in the HFR region and / or the LFR region are mutated into amino acids without charges. According to the invention, positive charge plaques on the CAR surface of an scFv sequence of a B7-H3 human-derived monoclonal antibody MGA271 are changed in a charged amino acid mutation manner, so that a B7-H3. CAR-T cell is optimized, and it is proved that the B7-H3. CAR-T cell optimized by PCP can effectively kill B7-H3 positive tumor cells in vivo and in vitro; and a new method and thought are provided for clinical targeted treatment of B7-H3 positive solid tumors.

The invention belongs to the technical field of gene editing, and discloses a base editor system and application. According to the invention, a heterologous peptide sequence is inserted into IscB protein, the obtained peptide embedded IscB is fused with deaminase or glycosylase to construct a base editor, and DNA base editing is carried out. According to the base editor system, the size limitation is overcome, and single AAV delivery is achieved; the editing efficiency is obviously improved; the broad-spectrum applicability is realized; the system optimization is more flexible; the method has efficient editing potential in vivo, and the off-target effect is reduced. The invention provides an important new strategy for hyperlipemia treatment and provides a basis for gene therapy of other hereditary diseases.

The invention relates to application of 1, 2, 3, 4, 6-O-pentagalloylglucose in preparation of a medicine for resisting cholestatic liver diseases, and belongs to the technical field of medicinal chemistry. The 1, 2, 3, 4, 6-O-pentagalloylglucose provided by the invention can be used for promoting bile acid excretion by reducing WDR6 protein expression. In-vivo and in-vitro experiments prove that the 1, 2, 3, 4, 6-O-pentagalloylglucose can be used for remarkably relieving the symptom of the cholestatic liver disease. In addition, the 1, 2, 3, 4, 6-O-pentagalloylglucose has no obvious toxic or side effect, and has no obvious influence on the liver function and the kidney function. The 1, 2, 3, 4, 6-O-pentagalloylglucose has a wide anti-cholestatic liver disease spectrum, and is suitable for various cholestatic liver diseases, such as primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and the like.

The invention provides novel compounds which are peptide hormone analogues, and which are useful in treating disorders such as diabetes and obesity. The compounds of the general sequence recited in the specification possess a tailored profile with regards to potency properties at the GIP receptor. With regard to in vivo properties, administration of example peptides of the invention have been shown, in animal models, to result in increased weight loss. Preferred compounds achieve this without reducing food intake significantly.

KLRB1 binding agents (in particular anti-KLRB1-antibodies and antigen binding portion thereof) with increased humanness and compositions thereof, as well as therapeutic methods of using the agents, e.g., for depleting cells or inhibiting cells or activating cells, (in particular, Th17, Th17.1, ex-Th17, Tc17, MAIT, iNKT, peTh2, ILC2, ILC3, NK cells, and / or neoplastic T or NK cells in vivo), for the treatment of autoimmune disease, allergic diseases, transplant rejection, hematologic malignancies, and cancer.

The invention discloses a lipid compound capable of being used for gene delivery, a preparation method of the lipid compound and application of the lipid compound in gene delivery. Also disclosed herein is a lipid nanoparticle comprising the lipid compound, a gene delivery composition comprising the lipid compound or the lipid nanoparticle. The lipid compounds, lipid nanoparticles and delivery systems herein enable efficient complexation, protection, intracellular and targeted delivery and release of biomolecules, such as oligonucleotides and nucleic acids, in vitro and in vivo tissues and organs.

Disclosed are an ecteinascidin compound and a use thereof. The present invention provides a compound as shown in formula (I), or a pharmaceutically acceptable salt, ester, stereoisomer, tautomer, polymorph, solvate, isotope-labeled compound, metabolite, or prodrug thereof. The compound provided by the present invention exhibits one or more effects selected from the following group: (1) having inhibitory activity on in vitro proliferation of tumor cells; (2) having in vivo antitumor effect; (3) having in vivo tumor-targeting ability; and (4) having good in vivo safety.

The invention discloses a depth physical parameter integrated network and method for lensless microscopic imaging, and the method comprises the steps: firstly building a physical forward model based on fractional Fourier transform, and quantizing a propagation distance into an adjustable fractional order parameter; secondly, constructing a multi-stage progressive network framework, wherein each stage comprises a physical model fidelity module and an image regularization updating module; a self-adaptive near-end network and a self-adaptive compression-excitation network are innovatively embedded in a regularization module, and real-time self-adaption of network parameters to imaging conditions is achieved; finally, end-to-end single-frame reconstruction is realized, complex amplitude information is directly recovered from a single intensity observation image, and retraining for different imaging parameters is not needed. According to the method, the reconstruction physical reliability, the noise robustness and the cross-scene generalization ability are remarkably improved, meanwhile, the lightweight real-time deployment requirement is met, and the method is suitable for lens-free microscopic imaging scenes such as biological living body observation and portable pathological diagnosis.

The application discloses a kind of carrier, kit and application for long-acting gene knockdown of animal parasitic nematode, belong to the field of animal parasitic disease prevention and control.The lentivirus vector in the application integrates specific coding sequence to the genome of the infected nematode, stably and continuously expresses short hairpin RNA (shRNA) in the nematode, efficiently produces primary single-stranded small RNA (siRNA), these siRNAs target homologous target gene mRNA to cause its degradation, realize stable and continuous gene silencing effect.The application breaks through the bottleneck of traditional animal parasitic nematode RNA interference (RNAi) technology with low efficiency and instability, significantly improves the timeliness of conventional RNAi, can be used to establish long-acting RNAi technology system of animal parasitic nematode, has application value in the research of host in vivo process such as nematode infection, parasitism and pathogenicity and animal parasitic nematode disease prevention and control.

The invention discloses a method for improving in-vivo and in-vitro antioxidant activity of pomegranate peel polyphenol extract through combined enzymolysis of tannase and beta-glucosidase, and relates to the technical field of food science and biology. The pomegranate peel polyphenol extract provided by the invention is obtained from pomegranate peel powder through solvent extraction. According to the present invention, tannase and beta-glucosidase are adopted to perform single or combined enzymolysis on the pomegranate peel polyphenol extract, and the determination on the in vitro antioxidant activity of the pomegranate peel polyphenol extract shows that the antioxidant activities of DPPH and ABTS after the combined enzymolysis are improved by 29.84% and 29.30% compared with the antioxidant activities of the untreated polyphenol extract; the UPLC-ESI-QTOF-MS is used for identifying and analyzing the components of the enzymatic hydrolysate, the content of macromolecular ellagic tannin is obviously reduced, and the content of micromolecular ellagic acid and gallic acid is increased. The enzymolysis polyphenol is applied to D-galactose induced oxidative stress mice, and the result shows that the oxidative damage relieving effect of the enzymolysis polyphenol on the mice is better than that of untreated polyphenol.

The invention particularly relates to application of a ganoderma lucidum exosome or a composition thereof in preparation of an anti-breast cancer product. The invention proves that the ganoderma lucidum exosome can be taken by breast cancer cells and exerts in-vitro activity of inhibiting proliferation and migration of the breast cancer cells and hindering repair of the breast cancer tumor cells, and in an in-vivo disease model, the ganoderma lucidum exosome also exerts the toxicity of the breast cancer tumor cells and effectively inhibits the process of the breast cancer. The research conclusion of the invention provides a development direction of taking the ganoderma lucidum exosome as an anti-breast cancer active component, and the ganoderma lucidum exosome has a good development prospect.

The invention discloses a gastroscope in-vivo detection time measuring method, and relates to the technical field of gastroscope detection, and the gastroscope in-vivo detection time measuring method comprises the following steps: obtaining a data set of in-vivo and in-vitro environment dichotomy; the method comprises the following steps of: constructing a binary classification network based on a Vision Transform; training a dichotomy network based on Vision Transformer by adopting a data set of dichotomy of in-vivo and in-vitro environments; for a complete gastroscope video frame sequence of the in-vivo retention time of the gastroscope to be detected, extracting a frame at a certain interval as a representative frame, sending all the representative frames into the trained Vision Transform-based binary classification network for classification, searching the last group of in-vivo frame serial numbers Ida from the outside to the inside, and determining the in-vivo retention time of the gastroscope to be detected. And the last group of in-vivo frame serial numbers Idb from in vivo to in vitro; and calculating the retention time in the gastroscope body. The automatic processing level is high, extra manual processing is not needed in the whole process, the workload can be greatly reduced, the time efficiency can be improved, and the problems of missed watching and wrong watching caused by careful manual retrospective observation in a traditional method can be solved.

The invention relates to the technical field of biology, and particularly provides a targeting carrier, a targeting drug, a preparation method and application. The targeting carrier comprises (a) a metal-polyphenol compound particle and (b) a targeting structure, and the targeting structure is connected with the outer surface of the metal-polyphenol compound particle. Under the condition that the effectiveness of the LNP based on the cationic lipid and / or the ionizable lipid is not lower than that of the LNP based on the cationic lipid and / or the ionizable lipid, the targeting carrier provided by the invention does not use the cationic lipid and the ionizable lipid, so that the toxicity is greatly reduced, the biological safety is remarkably improved, negative charge drugs are more favorably carried in a living body, the application range is wide, and the targeting carrier can be used for drugs with different sizes. The targeted drug can achieve high expression quantity of nucleic acid drugs, the biological safety is remarkably improved, the targeting property is good, and efficient treatment of various diseases can be achieved.

Provided are a recombinant human interleukin-11 mutant, and a conjugate of the mutant conjugated to a chemical molecule and a use thereof. The recombinant human interleukin-11 mutant achieves soluble expression in an Escherichia coli expression system by means of an SUMO sequence tandem fusion method. The conjugate is obtained by the site-specific conjugation of the mutant to the chemical molecule at a mutant amino acid residue in position W147 by means of a covalent bond. The chemical molecule is at least one of polyethylene glycol, an alkanoic acid aliphatic chain, and a hydrophilic high-molecular polymer containing an alkanoic acid aliphatic chain. The conjugate retains the binding capacity to human interleukin-11 receptor A while demonstrating significantly reduced binding capacity to human IL-6 signal transducer receptor. The conjugate shows the ability to block the signaling between human IL-11 and IL-11 RA and between human IL-11 and GP130 either in vivo or in vitro and can be used for the treatment of associated diseases with tissue fibrosis as a clinical manifestation caused by elevated primary or secondary IL-11.

The invention discloses an effectiveness analysis method of a drug entrapment material for treating intrauterine adhesion. The effectiveness analysis method comprises the following steps: performing multi-aspect research on the drug entrapment material and generating an effectiveness analysis result. In performance characterization, the morphology and pores of the material are analyzed by using microscopy, specific surface area and other technologies, the compatibility of the drug and the carrier is verified, and the physical state of the drug is detected; in-vitro analysis covers drug release kinetics, the release amount is measured in a simulated environment, and a curve is fitted; the biocompatibility evaluation refers to co-culture of a material leaching solution and cells, detection of cell activity and the like; implanting a medicine carrying material into the animal model in vivo, and evaluating the curative effect by using technologies such as image and pathology; and finally, integrating various results to obtain an entrapment material effectiveness analysis conclusion. According to the method, the limitation of traditional single-point testing is broken through, a full-chain evaluation model of structural characteristics-release behavior-biocompatibility-repair efficiency is constructed, and a scientific basis is provided for rational design and clinical transformation of intrauterine adhesion treatment materials.

The invention discloses an oligonucleotide intracellular nano delivery system based on polypeptide modification and application thereof. The system is composed of a periostin targeting sequence (SDSSD), a matrix metalloproteinase 2 (MMP2) response sequence (GPAGLLG), a cell penetrating sequence (RRRRRRRR, R9), a reactive oxygen species (ROS) scavenging and adhesion enhancing group (Gly-DOPA)) and a terminal dibenzocyclooctyne (DBCO) modified engineered polypeptide SDSSD-PEG5-YGFGG-GPAGLLG-R9-(G-DOPA) 3-K4-C-DBCO, and a target oligonucleotide miRNA-26a-A5-Azido modified by 5-polyadenylic acid (AAAAA) and an azide group (Azido), and the target oligonucleotide miRNA-26a-A5-Azido, the target oligonucleotide and assembling through a click chemical reaction and a non-covalent interaction. The nano system has good bone targeting, enzyme responsiveness, intracellular delivery effect and biological safety, can realize stable and efficient delivery of therapeutic oligonucleotides in vivo, and significantly improves the utilization efficiency and therapeutic potential of oligonucleotides. The oligonucleotide intracellular nano delivery system has a wide application prospect in the fields of clinical transformation and precise treatment of oligonucleotide drugs.