1794results about "Compounds screening/testing" patented technology

The invention belongs to the field of cosmetic detection, and discloses a cosmetic and cosmetic raw material sunscreen function evaluation method and application. According to the evaluation method, a sunscreen effect test is carried out on a test sample by using a non-contact administration device, wherein the test sample is a cosmetic finished product or a diluted cosmetic raw material; the test comprises evaluation of in-vitro sunscreen effect by skin cells, evaluation of in-vivo sunscreen effect by a zebra fish embryo model and result evaluation. According to the method, the sunburn-resistant effect is evaluated through expression of beta-galactosidase in human dermal fibroblasts and / or secretion of collagen, the sunburn-resistant effect is evaluated through the survival rate of human keratinocytes, the DNA damage condition or inflammatory factor secretion and the lethal / teratogenic condition of zebra fish embryos, and multi-layer and all-around sunburn-resistant effect evaluation is achieved. The method provided by the invention is suitable for evaluating the sunscreen function of various sunscreen products, has accuracy and practicability, and provides an important technical basis for research and development, quality control and performance optimization of sunscreen cosmetics.

Isolated or recombinant EphA5 or GRP78 targeting antibodies are provided. In some cases, antibodies of the embodiments can be used for the detection, diagnosis and / or therapeutic treatment of human diseases, such as cancer. A method of rapidly identifying antibodies or antibody fragments for the treatment of cancer using a combination of in vitro and in vivo methodologies is also provided.

The invention belongs to the technical field of biological medicines, and provides application of DRAM1 as a diagnosis and treatment target for resisting non-alcoholic fatty liver disease related hepatocellular carcinoma in preparation of a kit, a carrier and a medicine aiming at the problem of lack of effective treatment targets of NAFLD-related HCC. As a target spot for resisting the non-alcoholic fatty liver disease related hepatocellular carcinoma, the expression level of the DRAM1 in liver tissues of non-alcoholic fatty liver disease related hepatocellular carcinoma patients and mice is increased. According to the application disclosed by the invention, research is developed aiming at the effect of the DRAM1 in the generation and development of NAFLD-related HCC, the analysis of TCGA liver cancer queue data and a GSE164760 data set is taken as an entry point, the influence of the DRAM1 on the diagnosis and prognosis of the liver cancer is comprehensively analyzed, and verification is carried out through a mouse in-vivo experiment, so that a new thought and a new target spot are provided for clinical diagnosis and treatment of the liver cancer.

The invention discloses a method for targeted creation of a fast-growing new tilapia strain, and belongs to the technical field of fish cultivation. The method specifically comprises the following steps: (1) taking a fragment, as shown in SEQ ID NO.1, on a third exon of a pomc gene as a gRNA target sequence; (2) designing and synthesizing a gRNA primer sequence; (3) amplifying by adopting the gRNA primer sequence and the gRNA plasmid, and then transcribing and purifying to obtain a gRNA fragment; (4) transferring the gRNA fragments into fertilized eggs of tilapia mossambica through gene editing to obtain F0-generation positive fish; and (5) hybridizing the F0-generation positive male fish with the wild-type female fish, screening out F1-generation parent fish, and culturing the F1-generation parent fish to obtain F2-generation tilapia with homozygous deletion mutation. According to the invention, the pomc homozygous knockout line is established in the Nile tilapia mossambica for the first time, the new fast-growing line is a complete gene function deletion model, the cost is lower, the efficiency is higher, and the phenotype can be stably inherited.

The invention discloses a method for constructing a Ddx58-R109C point mutation mouse model by using a CRISPR / Cas9 gene editing technology and an application of the Ddx58-R109C point mutation mouse model. The method comprises the following steps: (1) target construction: searching a CDS region of a Ddx58 gene, determining an exon part, and determining a gene mutation site; (2) obtaining a fertilized egg, and injecting Cas9mRNA, gRNA and donor oligo into the fertilized egg of the C57BL / 6J mouse together in vitro through a microinjection technology to obtain an F0-generation hybrid mouse; (3) mating the F0-generation hybrid mouse with the wild type mouse to obtain an F1-generation mouse; (4) the F1-generation heterozygous mice which are identified to be positive are subjected to mating, and homozygous Ddx58-R109C mutant type and wild type mice can be obtained by breeding obtained offspring; (5) phenotypic analysis shows that Ddx58-R109C point mutation mice can have pathological changes of systemic lupus erythematosus and lupus nephritis; the invention can provide an effective research approach and method for researchers to deeply explore the action mechanism of Ddx58-R109C mutation in diseases, and has important significance for explaining the pathogenesis of systemic lupus erythematosus and researching and developing targeted therapeutic drugs.

The present invention belongs to the field of cosmetics detection, and discloses a method for evaluating the sun protection function of cosmetics and cosmetic raw materials and its application. This evaluation method uses a non-contact drug delivery device to test the sun protection effect of the test samples, and the test samples are finished cosmetics or diluted cosmetic raw materials; the tests include evaluating the in vitro sun protection efficacy by skin cells, evaluating the in vivo sun protection efficacy by the zebrafish embryo model, and result evaluation. This method evaluates the anti-aging effect of sun protection through the expression of β-galactosidase and / or the secretion of collagen in human dermal fibroblasts, and evaluates the sunburn prevention effect through the survival rate of human keratinocytes, DNA damage, or the secretion of inflammatory factors and the lethal / teratogenic conditions of zebrafish embryos, realizing multi-level and all-round evaluation of the sun protection efficacy. The method provided by the present invention is applicable to the evaluation of the sun protection function of various sun protection products, has accuracy and practicability, and provides an important technical basis for the research and development, quality control, and performance optimization of sun protection cosmetics.

The invention discloses a spirulina platense skin extract as well as a preparation method and application thereof, and relates to the technical field of biomedicine. The obscured spirulina skin extract is rich in various active ingredients including collagen family members, viscose protein, C1Q complement protein, fibronectin and the like, and the ingredients complement and promote one another, so that the extract has remarkable effects in the aspects of skin aging resistance, skin injury repair and the like; therefore, the method has a wide application prospect in medicine research and development, cosmetics and functional foods. According to the extraction method of the skin protein of the obtuse spirulina, the sample is subjected to rapid freeze thawing treatment, and the steps of mechanical crushing, ultrasonic-assisted separation and multiple filtration are combined, so that the influence on the activity of the product is avoided, and various compound proteins can be obtained; the pH value of a buffer solution is adjusted, the property of the extract is further optimized, and the extract is more suitable for human skin, is sterile and can be directly used as a product raw material, so that large-scale production is realized, and industrial application of the obtuse spirulina skin extract is promoted.

The invention belongs to the technical field of biology, and particularly relates to a cryptosporidium parvum infection immunosuppression mouse model and a construction method thereof. Aiming at the problem that the development of cryptosporidiosis drugs and vaccines is seriously limited due to the fact that no model for successfully infecting mice with cryptosporidium parvum exists at present, the invention provides the construction method of the cryptosporidium parvum infection immunosuppression mouse model, which comprises the following steps: firstly, carrying out gavage treatment on the mice for 4-7 days by adopting cyclophosphamide; constructing to obtain an immunosuppressive mouse; feeding PBS (Phosphate Buffer Solution) containing cryptosporidium parvum oocysts through the mouth, and infecting for 7-21 days; and when oocysts are continuously detected from excrement of the mouse and the content of the oocysts is higher than the infection amount, constructing the cryptosporidium parvum infection immunosuppression mouse model. The cryptosporidium parvum infection immunosuppression mouse model is successfully constructed, can be used for subsequent drug and vaccine development tests for cryptosporidium parvum diseases, and has a good application prospect.

The present invention provides a non-human animal expressing a human or chimeric (e.g., humanized) GDF8 protein and methods of use thereof.

The invention discloses a preparation method and application of a self-reactive animal model. An autoreactive animal model is constructed based on an SWHEL system, it is found through the model that MTCH2 is a key target for regulating and controlling B cell autoreactivity, deletion of MTCH2 will cause generation of a large number of autoreactive B cells subjected to antibody category conversion, the disease risk is increased, and a basis is provided for research of B cell autoreactivity related mechanisms.

Provided in the present invention are a non-human animal expressing a human or chimeric (e.g. humanized) CFB protein and a use method thereof. Further provided in the present invention are a non-human animal genome, a humanized CFB gene, and a cell, tissue, organ or non-human animal containing the non-human animal genome and the humanized CFB gene. The non-human animal obtained by the present application successfully expresses the human or humanized CFB protein, wherein the protein can be cleaved by CFD, bind to C3b, and achieve a similar effect as in a human body. In addition, the non-human animal obtained in the present application has a complete renal function state and normal blood biochemical indexes. Even more rarely, potential diseases known in the prior art which have been observed in some other transgenic mice do not occur in the non-human animal.

The invention belongs to the technical field of microbial medicine, and provides a primary multidrug resistance human far-end bile duct cancer cell line CBC3T-6 Homo sapiens and application thereof.The human far-end bile duct cancer cell line CBC3T-6 Homo sapiens is separated from differentiated adenocarcinoma in a far-end bile duct, the human far-end bile duct cancer cell line CBC3T-6 Homo sapiens is already subcultured to 50 generations at present, the long-term in-vitro culture character is stable, and on the premise that the biological characteristics of bile duct cancer are reserved, the human far-end bile duct cancer cell line CBC3T-6 Homo sapiens can be used for preparing the primary multidrug resistance human far-end bile duct cancer cell line CBC3T-6 Homo sapiens. The compound has the characteristics of short multiplication time, high mouse subcutaneous tumor formation rate and the like, and has different degrees of drug resistance to gemcitabine, 5-fluorouracil, oxaliplatin and cis-platinum in first-line anti-cancer drugs for bile duct cancer. The method not only enriches an extrahepatic bile duct cancer cell bank, provides a new cell model for basic research and clinical drug research and development of bile duct cancer, but also provides powerful scientific research data for research developed based on the genetic background of Chinese population. Therefore, the primary multidrug resistant cell line has higher scientific research and clinical application values.

The invention belongs to the technical field of biology, and particularly relates to an SLC44A1 gene and / or SLC44A5 gene knockout animal model as well as a construction method and application thereof. The construction method of the animal model comprises the following steps: deleting exon regions from the fourth exon region to the thirteenth exon region of the SLC44A1 gene and / or the second exon region of the SLC44A5 gene in mouse brain oligodendroglia cells in a high-efficiency manner by utilizing gene editing and a Cre-loxP recombinase system, so as to realize the knockout of a target gene. The animal model constructed by the invention can be used for researching the regulation mechanism of the choline transporters (SLC44A1 and SLC44A5) on myelin sheath formation, deeply knowing the biological functions of the choline transporters (SLC44A1 and SLC44A5), simulating the occurrence and development processes of human related diseases, revealing the pathogenesis of the related diseases, providing a new thought for prevention and treatment of brain myelin sheath dysplasia, and providing a new foundation for the prevention and treatment of brain myelin sheath dysplasia. And an effective drug or a treatment mode aiming at the disease is screened by utilizing a gene knockout animal model, so that a new choice is provided for clinical treatment of the disease.

The invention belongs to the technical field of biomedicine, and particularly relates to application of GABA (gamma-aminobutyric acid) driven by lactobacillus rhamnosus to treatment of cerebral malaria of mice. According to the invention, the obviously enriched lactobacillus muricatum is found, and the lactobacillus muricatum is proved to be capable of generating GABA (gamma-aminobutyric acid). Afterwards, on the mouse cerebral malaria model, under the condition that the lactobacillus rhamnosus and the GABA are independently used or auxiliary dihydroartemisinin is used, the effect of the lactobacillus rhamnosus and the GABA on improving and treating the mouse cerebral malaria is evaluated. Results show that the strain and the metabolite GABA thereof can effectively improve behavioristics of mice and immune pathological injuries of all organs, reduce protozoemia and prolong the lifetime of the mice whether the strain is independently used or combined with dihydroartemisinin, and can effectively treat cerebral malaria of the mice compared with the strain which is independently used with drugs. The invention provides a brand-new solution for treating severe malaria, especially human brain malaria, caused by malignant malaria from the perspective that the probiotics drive metabolites of the probiotics to assist the anti-malarial drug in treating rat brain malaria.

In some aspects, the disclosure provides humanized immunodeficient mouse models that support long term transplantation and function of human T cells, natural killer cells, and bone marrow cells without the need for conditioning.

The invention provides a hydrogel microneedle patch for treating oral ulcer and a preparation method, and belongs to the technical field of biomedical engineering. The technical problems that in the traditional oral ulcer administration process, medicine is difficult to retain at the focus for a long time, is easily scoured by saliva and is influenced by tongue and cheek movement are solved. According to the technical scheme, the method comprises the following steps: 1) designing and preparing a microneedle patch mold; (2) synthesizing drug-loaded polydopamine nano particles; (3) preparing a microneedle patch; and 4) evaluating the performance of the microneedle patch. The invention has the following beneficial effects: on one hand, the combination of the drug-loaded nanoparticles and the hydrogel microneedle array can reduce the dosage through drug sustained release; and on the other hand, the problems of high drug instability, low targeting property, poor bioavailability and hindering treatment effect are effectively solved, and the preparation can be widely applied to the fields of drug sustained release, wound healing, tissue engineering and the like.

The invention provides a composition with an instant and long-acting anti-aging effect and application thereof. The composition comprises a component A, a component B and a component C, the mass ratio of the raw materials is (1-10): (1-4): (0.05-0.2); the component A is prepared from the following components in parts by weight: 0.01 to 0.5 part of acetyl octapeptide-3, 0.01 to 0.5 part of dipeptide diaminobutyryl benzyl amide diacetate, 0.001 to 0.2 part of arginine / lysine polypeptide, 0.3 to 1 part of caprylyl glycol and 96 to 100 parts of water; the component B is prepared from the following components in parts by weight: 0.001 to 0.2 part of soluble collagen, 5 to 30 parts of glycerol, 0.01 to 0.5 part of sodium dihydrogen phosphate, 0.001 to 0.2 part of disodium hydrogen phosphate and 65 to 100 parts of water; and the component C is tripeptide-29. According to the invention, the quadruple wrinkle fading polypeptide is adopted to block wrinkles in a multi-target full-link manner, so that the product has a very good effect of fading various wrinkles in real time.

The present invention is directed to antagonistic antibodies and antigen binding fragments thereof having binding specificity for PACAP. These antibodies inhibit, block or neutralize at least one biological effect associated with PACAP, e.g., vasodilation. In exemplary embodiments these antibodies and antigen binding fragments thereof may comprise specific VH, VL, and CDR polypeptides described herein. In some embodiments these antibodies and antigen binding fragments thereof bind to and / or compete for binding to specific epitope(s) on human PACAP. The invention is further directed to using these antagonistic anti-PACAP antibodies, and binding fragments thereof, for the diagnosis, assessment, and treatment of diseases and disorders associated with PACAP and conditions where antagonism of PACAP-related activities, such as vasodilation, mast cell degranulation, and / or neuronal activation, are therapeutically beneficial, e.g., headache and migraine indications.

The invention discloses a lipid nanoparticle-coated MOTS-c peptide and a derivative thereof, and is characterized by comprising a lipid nanoparticle preparation and drug loading process, which specifically comprises the steps of lipid nanoparticle preparation, targeting ligand grafting, liposome characterization verification and in-vivo evaluation of targeting efficiency. The preparation process of the lipid nanoparticles comprises the following steps: step 1, dissolving hydrogenated soybean phosphatidylcholine (HSPC), cholesterol (Chol) and polyethylene glycol modified phospholipid (DSPE-PEG-COOH) in a mixed solvent of chloroform and methanol according to a molar ratio of 10: (5-15): (2-10): (0.5-3); according to the invention, a specific type of lipid nanoparticles are designed to wrap the mitochondrial peptide and the derivative of the mitochondrial peptide. The nano-particles not only can effectively protect peptide drugs from being degraded by an in-vitro environment, but also can realize lung targeting delivery through optimized particle size and surface characteristics, and the targeting property of the drugs is enhanced by modifying specific lung targeting ligands on the surfaces of the lipid nano-particles, so that the lipid nano-particles are ensured to play a role preferentially in the lung.

The invention provides a blood fat reducing polypeptide as well as a screening method and application thereof, and belongs to the field of polypeptides. The blood fat reducing polypeptide provided by the invention comprises at least one of 116 polypeptides with amino acid sequences of FFPFF, VFFFPF, PFFFF, AFFFPFF, LFFFPFY and the like. The blood fat reducing polypeptide provided by the invention can effectively reduce blood fat, has no obvious toxic or side effect, shows good inhibitory activity on steroid esterase and lipase in an in-vitro enzyme activity test, and also can effectively reduce blood fat in an animal in-vivo experiment; and no obvious toxic or side effect is shown in toxicity prediction and animal in-vivo models.

The invention provides a chronic hypoperfusion animal model construction method and application thereof, and relates to the technical field of biomedicine. The construction method of the chronic hypoperfusion animal model, provided by the invention, aims at brain capillary endothelial cells, and the constructed chronic hypoperfusion animal model is global and lasting brain hypoperfusion, has no infection or death risk and is low in cost. The animal model constructed by using the method is more convincing in the aspects of reperfusion research and drug curative effect evaluation.

The invention belongs to the technical field of biotechnology and animal models, and discloses a double-person-derived mouse model for simulating a tumor immune microenvironment and a construction method and application thereof. The method comprises the following steps: firstly, pretreating NSG immunodeficient mice by adopting low-dose whole-body irradiation in combination with double-antibody targeted bone marrow depletion, and transplanting CD34 + hematopoietic stem cells from the same human donor to complete human immune system reconstruction; separating tumor primary cells, tumor-related fibroblasts and tumor vascular endothelial cells of the same donor, performing three-dimensional co-culture to obtain homologous human tumor organs, and performing in-situ inoculation to immune reconstruction mice to obtain a target model. The core defects of MHC mismatching, low immune reconstruction efficiency, poor tumor immune microenvironment simulation degree, low clinical consistency and the like of an existing model are overcome, and the method can be used for tumor immune treatment drug screening, microenvironment mechanism research and personalized tumor treatment scheme verification.

The invention provides an application of WNT7B in construction of a myopia animal model. Homologous genes wnt7ba and wnt7bb of the WNT7B in the zebra fish are knocked out or knocked down by applying a CRISPR / Cas9 gene editing technology, an animal model of which the eye axis length is remarkably increased, the eyeball movement frequency is remarkably reduced and the light response is reduced is obtained, and the result shows that the WNT7B is related to the high myopia. The model provides a favorable tool for pathogenesis and drug screening of high myopia, and has a good application prospect.

The invention discloses a construction method and application of a caenorhabditis elegans inflammation model, belongs to the technical field of model biology, and provides a construction method of a caenorhabditis elegans inflammation model, which comprises the following steps: putting L1-stage caenorhabditis elegans into a lipopolysaccharide solution, and carrying out induced culture to obtain induced cultured caenorhabditis elegans; placing the caenorhabditis elegans in a chromosome system, performing staining culture and centrifugation to obtain dyed caenorhabditis elegans, and placing the dyed caenorhabditis elegans on a culture medium for recovery to obtain the caenorhabditis The surface of the caenorhabditis elegans is provided with a transparent cuticle anatomical structure, the intestinal barrier damage condition is easy to observe after the intestinal tract is dyed by a dye, and the cell proliferation, tissue development and tissue integrity of the caenorhabditis elegans are easy to carry out fluorescence microscope and morphological analysis. A caenorhabditis elegans inflammation model is constructed through lipopolysaccharide induction, and a new experimental animal model is provided for screening anti-inflammatory drugs.

The invention belongs to the technical field of animal models, and provides a construction method and application of a kidney stone induced acute kidney injury mouse model. The construction method of the kidney stone induced acute kidney injury mouse model comprises the following steps: firstly, fasting and depriving water of a mouse for 12 hours, then injecting 10mg / kg sodium oxalate solution into the body of the mouse in an intraperitoneal injection manner, and meanwhile, replacing drinking water with 3wt% sodium oxalate solution, so that the kidney stone induced acute kidney injury mouse model can be obtained 24 hours later. The sodium oxalate solution is used as the lithigenic agent, the effect is obvious and reliable, the action is strong, the stability and the repeatability are high, the obtained acute kidney injury mouse model is used for subsequent AKI pathogenesis and AKI generation experiment research or drug screening, the observation is obvious, and the method is simple.

The invention discloses a humanized osteoporosis mouse model and a construction method thereof, and belongs to the technical field of biotechnology and animal models. The invention aims at the core defects of large species difference, insufficient humanization degree, low pathological simulation degree, unstable phenotype and the like of the existing osteoporosis model. The humanized osteoporosis mouse model is constructed through five core steps of experimental animal pretreatment, collagen-nano hydroxyapatite bionic scaffold preparation and cell pre-implantation, immune-bone metabolism double-derived system construction, progressive osteoporosis induction and model identification and verification. According to the method, double-person origination of immune and bone metabolism systems is realized for the first time, the colonization rate and survival time of human cells are greatly improved, the pathological process of clinical postmenopausal osteoporosis is accurately simulated, the phenotype of the model is stable and uniform, the reactivity matching degree with clinical drugs is high, and the method can be widely applied to research and development of anti-osteoporosis drugs and research of pathological mechanisms.

The invention provides a dilated cardiomyopathy zebrafish model and a construction method and application thereof, and belongs to the technical field of biology.The dilated cardiomyopathy zebrafish model is constructed by overexpressing miR-16-5p in myocardial cells of zebrafish, and the sequence of miR-16-5p is shown as SEQ ID NO.1; the invention further provides a construction method of the dilated cardiomyopathy zebra fish model. The invention constructs the dilated cardiomyopathy zebrafish model of overexpression miR-16-5p in myocardial cells for the first time, and the dilated cardiomyopathy zebrafish model can be used for screening drugs for resisting dilated cardiomyopathy.

The invention discloses a method for establishing an animal model for age-related retinopathy caused by lipid metabolism disorder, and the animal model is obtained by specifically knocking out Lss genes from mouse retinal pigment epithelium (RPE) cells by means of a CRISPR / Cas9 gene editing technology. The age-related retinopathy model mouse constructed by the invention shows a retinopathy phenotype with retinal lipid deposition and reduced visual function at the age of 5 months, and the retinopathy is further aggravated along with the increase of the age of the mouse and is similar to the phenotype of age-related retinopathy related to lipid metabolism disorder clinically; and an ideal and effective animal model is provided for researching age-related retinopathy.

The invention relates to an application of a CTHRC1 inhibitor in preparation of a medicine for preventing and / or treating arthritis. Specifically, the invention provides application of an inhibitor or an antagonist of a CTHRC1 gene or a protein thereof, the inhibitor or the antagonist is used for preparing a composition or a preparation, and the composition or the preparation is used for (a) preventing and / or treating arthritis-related diseases; and / or (b) inhibiting cartilage cell senescence.

The invention provides a GelMA microneedle patch loaded with chromogenic gold nano bipyramids and a preparation method thereof.The method comprises the steps that citric acid, chloroauric acid and a CTAC solution are mixed, then sodium borohydride is added, and a seed solution is obtained through stirring and standing; mixing chloroauric acid, silver nitrate, hydrochloric acid and CTAB (cetyltrimethyl ammonium bromide), and sequentially adding ascorbic acid and the seed solution to obtain a growth solution; carrying out centrifugation, morphology regulation and chemical etching purification to obtain a chromogenic gold nano bipyramid solution; the preparation method comprises the following steps: reacting gelatin with methacrylic anhydride in PBS, dialyzing and freeze-drying to obtain GelMA; dissolving GelMA in the gold nanoparticle bipyramid solution, and adding a photoinitiator LAP to obtain a mixed precursor solution; and the GelMA microneedle patch loaded with the gold nano bipyramid is prepared through mold casting, centrifugation, ultraviolet light crosslinking and drying demolding. The microneedle extraction and gold nano bipyramid color development integrated scheme is initiated, blood sampling is not needed, the dermis interstitial fluid is extracted in a minimally invasive mode through the microneedle, detection pain and trauma are reduced, the cross infection risk of blood treatment is avoided, and the microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle