110 results about "Mediator" patented technology

The present invention relates to CRISPR / Cas based biosensing materials, assays, and methods. Specifically, the present technology relates to CRISPR / Cas-based ultra-sensitive detection methods for nucleic acid assays using specific molecular constructs, including constructs referred to as nucleic acid mediators, comprising single-stranded and double-stranded nucleic acid sequences of a cyclic conformation, and palindromic oligonucleotides. The materials and methods according to the invention can also be used to enhance the sensitivity of existing bioassays.

The present disclosure provides genetically modified iPSC-derived γδT cells and their precursors. A double genomic disruption in the suppressor of cytokine signaling 1 (SOCS1) gene and the cytokine-inducible sh2-containing protein (CISH) gene are provided, as is a triple genomic disruption in genes for SOCS1, CISH, and Bcl-2 interacting mediator of cell death (BIM), as is a quadruple genomic disruption in genes for SOCS1, CISH, BIM, and cell surface death receptor (FAS), as is a quintuple genomic disruption in genes for SOCS1, CISH, BIM, β-2-Microglobulin (B2M), and class II transactivator (CITTA), as is a sextuple genomic disruption in genes for SOCS1, CISH, BIM, B2M, CITTA, and FAS. Also provided is genetically modified iPSC-derived γδT cells and their precursors with improved proliferation and tumor killing activity. Also provided are genetically modified iPSC-derived γδT cells and their precursors further comprising CD19 CAR. The present disclosure further provides methods making and using such cells, as well as gene editing systems.

Lymphedema is characterized by the accumulation of protein-rich interstitial fluid, lipids and a significant inflammatory cell infiltrate in the limb. It causes a significant morbidity and is a common disabling disease affecting more than 250 million people worldwide, however there is no curative treatment for lymphedema. Here, the inventors found that dermolipectomies from patient with lymphedema exhibit inflamed gene expression profile compared to normal arm on same patient. After lipidomic analysis, the inventors identified severe decrease in arachidonic acid-derived lipid mediators generated by the 15-lipoxygenase (15-LOX) in lymphedematous arms. Using a mouse model of lymphedema, they reproduced the etiology of the human pathology including the loss of specialized pro-resolving lipid mediators that play essential roles in resolution of inflammation. This was associated with a lack of regulatory T cells (Treg) recruitment in the injured limb adipose tissue. Importantly, the inventors identified the lymphatic endothelial 15-LOX was responsible for the chemoattraction and transendothelial migration of Tregs. These results were confirmed by an aggravation of lymphedema and deterioration of the lymphatic network in an original transgenic mouse model in which ALOX15 gene is selectively deleted in the lymphatic system. Importantly, this was reversed by the injection of 15-LOX expressing lentivectors. These results provide evidence that lymphatic lipoxygenase may represent a novel therapeutic target for lymphedema by serving as a mediator of Treg invasion into lymphedematous adipose tissue.

The present disclosure provides genetically modified iPSC-derived γδT cells and their precursors. A double genomic disruption in the suppressor of cytokine signaling 1 (SOCS1) gene and the cytokine-inducible sh2-containing protein (CISH) gene are provided, as is a triple genomic disruption in genes for SOCS1, CISH, and Bcl-2 interacting mediator of cell death (BIM), as is a quadruple genomic disruption in genes for SOCS1, CISH, BIM, and cell surface death receptor (FAS), as is a quintuple genomic disruption in genes for SOCS1, CISH, BIM, β-2-Microglobulin (B2M), and class II transactivator (CIITA), as is a sextuple genomic disruption in genes for SOCS1, CISH, BIM, B2M, CIITA, and FAS. Also provided is genetically modified iPSC-derived γδT cells and their precursors with improved proliferation and tumor killing activity. Also provided are genetically modified iPSC-derived γδT cells and their precursors further comprising CD19 CAR. The present disclosure further provides methods making and using such cells, as well as gene editing systems.

A bioelectrode comprising: a complex compound composed of a metal and a ligand; a mediator having an anionic functional group; and an electroconductive material.

The embodiments of the present disclosure relate to decreasing the bioavailability of one or more target biomolecules by providing a composition that comprises a recombinant plasmid with one or more sequences of micro interfering ribonucleic acid (miRNA). When the recombinant plasmid interacts with a target cell, it causes the target cell to upregulate production of the miRNA, which then decreases the bioavailability of the target biomolecule. In some embodiments of the present disclosure, the target biomolecule is a cytokine or other mediator molecule of an inflammatory response.

The invention discloses a front door adjustment-based harmful modal cause detection depolarization method, which comprises the following steps of: constructing a structural causal model, creating a back door path between a modal cause and a harmful label by using unobserved confounding factors, and eliminating harmful modal cause detection through front door adjustment; the front door adjustment then blocks the back door path by introducing reasoning as an intermediary between the memetic and the tag. The method comprises the following steps: decomposing the causal effect of a medal factor on a harmful tag into the influence of the medal factor on an intermediary, quantifying by adopting a multi-modal large-scale language model with different beam searches to calculate the probability of each reasoning sequence and the influence of the intermediary on the tag, and performing effective approximation through a normalized weighted geometric averaging method; finally, post-interpretation is synthesized from the inference sequence and the predictive tag using a large language model. According to the scheme, the most advanced performance is achieved while information interpretation is provided.

Provided herein, inter alia, are compositions comprising one or more substantially pure strains of bacteria as well as methods of making and using the same to treat and / or prevent one or more immune system related disorders and to regulate the production of one or more immune system function mediators in a subject in need thereof.

The embodiments of the present disclosure relate to decreasing the bioavailability of one or more target biomolecules by providing a composition that comprises a recombinant plasmid with one or more sequences of micro interfering ribonucleic acid (miRNA). When the recombinant plasmid interacts with a target cell, it causes the target cell to upregulate production of the miRNA, which then decreases the bioavailability of the target biomolecule. In some embodiments of the present disclosure, the target biomolecule is a cytokine or other mediator molecule of an inflammatory response.

A family of bioactive compounds identified in self-resolving inflammatory exudates is disclosed. The compounds give UV chromophores characteristic of a conjugated triene double bond system coupled to an auxochrome allylic to the triene. Further elucidation of the compounds reveals that they have a resolvin backbone conjugated to a peptide or amino acid moiety via an auxochrome. In some embodiments the auxochrome is sulfur. However, the auxochrome may be NH, CH2 or O. The compounds have potent bioactivity, in vitro, and, in vivo, including promoting resolution of infection, stimulating macrophage phagocytosis of bacteria; protecting tissues from neutrophil mediated damage, promoting tissue repair and regeneration and preventing or limiting second organ reflow / reperfusion damage.

The integrin family of cell adhesion molecules has emerged as key mediators of tissue fibrosis. A pharmacological inhibitor of multiple integrin subtypes is required to produce meaningful effects on delaying or inhibiting the progression of fibrosis. Monoclonal antibodies recognizing multiple integrins with potent neutralizing activity and having human and mouse cross-reactivity are described. In particular, monoclonal antibodies that bind human αvβ1, αvβ3, αvβ5, αvβ36, αvβ38, and α5β1 integrins and mouse αvβ1, αvβ3, αvβ5, αvβ6, and αvβ8 integrins are described.

The embodiments of the present disclosure relate to decreasing the bioavailability of one or more target biomolecules by providing a composition that comprises a recombinant plasmid with one or more sequences of micro interfering ribonucleic acid (miRNA). When the recombinant plasmid interacts with a target cell, it causes the target cell to upregulate production of the miRNA, which then decreases the bioavailability of the target biomolecule. In some embodiments of the present disclosure, the target biomolecule is a cytokine or other mediator molecule of an inflammatory response.

Cas-protein-ready tau biosensor cells, CRISPR / Cas synergistic activation mediator (SAM)-ready tau biosensor cells, and methods of making and using such cells to screen for genetic modifiers of tau seeding or aggregation are provided. Reagents and methods for sensitizing such cells to tau seeding activity or tau aggregation or for causing tau aggregation are also provided.

The embodiments of the present disclosure relate to decreasing the bioavailability of one or more target biomolecules by providing a composition that comprises a recombinant plasmid with one or more sequences of micro interfering ribonucleic acid (miRNA). When the recombinant plasmid interacts with a target cell, it causes the target cell to upregulate production of the miRNA, which then decreases the bioavailability of the target biomolecule. In some embodiments of the present disclosure, the target biomolecule is a cytokine or other mediator molecule of an inflammatory response.

The embodiments of the present disclosure relate to decreasing the bioavailability of one or more target biomolecules by providing a composition that comprises a recombinant plasmid with one or more sequences of micro interfering ribonucleic acid (miRNA). When the recombinant plasmid interacts with a target cell, it causes the target cell to upregulate production of the miRNA, which then decreases the bioavailability of the target biomolecule. In some embodiments of the present disclosure, the target biomolecule is a cytokine or other mediator molecule of an inflammatory response.

The invention relates to a method for detecting at least one target nucleic acid sequence by means of a method for detecting at least one target nucleic acid sequence, comprising the steps of: i. Providing at least one target sequence-unspecific modular reporter complex comprising at least one label and at least two oligonucleotides, namely, i. a base strand comprising, 1. at least one mediator binding site, 2. at least one signal initiation oligo binding site, ii. at least one signal initiation oligo, wherein optionally the signal initiation oligo binding site of the base strand and the at least one signal initiation oligo are hybridized to each other but not covalently bonded and together form a signal complex, j. Providing at least one mediator probe, wherein the mediator probe comprises an oligonucleotide having at least one probe sequence and at least one mediator sequence, wherein the at least one probe sequence exhibits an affinity for at least one target nucleic acid sequence, and the at least one mediator sequence exhibits an affinity for at least one mediator binding site on the base strand of the at least one target sequence-unspecific modular reporter complex, k. PCR amplification of at least one nucleic acid sequence, I. Binding of a probe sequence of at least one mediator probe to at least one target nucleic acid sequence, m. Cleavage of the probe sequence of the at least one mediator probe bound to the at least one target nucleic acid sequence by a PCR polymerase, wherein the mediator sequence is released, n. Binding of at least one released mediator sequence to a mediator binding site of the at least one target sequence-unspecific modular reporter complex, o. Extension of the sequence of at least one mediator sequence bound to a mediator binding site by a PCR polymerase, wherein the bond is broken or prevented by hybridization of the at least one signal initiation oligo binding site and the at least one signal initiation oligo, thereby initiating a signal change, p. Detection of at least one signal change as evidence of the at least one target nucleic acid sequence.

The present invention discloses a laccase, its gene and application, belonging to the technical field of genetic engineering. The laccase gene of the present invention is obtained by codon optimization of the laccase gene of Cerrena unicolor, and the nucleotide sequence is as shown in SEQ ID NO.2. The laccase gene provided by the present invention is recombinantly expressed by transforming Aspergillus niger, and high-activity laccase can be mass-produced industrially. The highest enzyme activity in shake flask culture reaches 39 U / ml, and after culturing in a 7L fermenter for 125 h, the total laccase activity reaches 9234 U / ml. At the same time, the laccase provided by the present invention and the mediator methyl syringate have a significant destructive effect on zearalenone, which is beneficial to grain transportation and storage.

The embodiments of the present disclosure relate to decreasing the bioavailability of one or more target biomolecules by providing a composition that comprises a recombinant plasmid with one or more sequences of micro interfering ribonucleic acid (miRNA). When the recombinant plasmid interacts with a target cell, it causes the target cell to upregulate production of the miRNA, which then decreases the bioavailability of the target biomolecule. In some embodiments of the present disclosure, the target biomolecule is a cytokine or other mediator molecule of an inflammatory response.

The invention discloses a sequence optimization method for improving the stability of circular RNA, application and a product, and belongs to the technical field of biotechnology and molecular biology. In order to solve the problem that the existing circular RNA is easy to be specifically degraded by RNAseK and lysosome after entering a cell, synonymous mutation optimization is carried out on an open reading frame of a target gene of the circular RNA by identifying nucleic acid motifs (a first type of nucleic acid motifs and a second type of nucleic acid motifs) identified by two degradation mechanisms. The optimized circular RNA is prepared by means of in-vitro cyclization of an anabaena I-type intron self-splicing mediator, after cells are transfected, the intracellular RNA expression level of the circular RNA is remarkably improved compared with that of a wild type, and the target protein expression efficiency is also remarkably improved. The intracellular stability and expression efficiency of the circular RNA are remarkably enhanced, and the method can be widely applied to the scenes of gene expression regulation, protein synthesis, gene therapy, vaccine development and the like.

This application relates to a biosensing electrode with sarcosine oxidase-directed modification, its preparation method, and its application in the field of biosensing technology. The biosensing electrode includes: a metal electrode, and a DNA-enzyme composite nanostructure connected to the metal electrode; the DNA-enzyme composite nanostructure includes a DNA electron transport module and an enzyme catalysis module; the DNA electron transport module includes a DNA sheet structure and a mediator embedded in the DNA sheet structure; the enzyme catalysis module includes a sarcosine oxidase substrate complex, which is connected to the DNA sheet structure; the sarcosine oxidase substrate complex, the mediator-containing DNA sheet structure, and the metal electrode are spatially ordered in the sequence of sarcosine oxidase substrate complex – mediator-containing DNA sheet structure – metal electrode. This biosensing electrode, under the condition of introducing a mediator, can improve the electron transport rate, thus exhibiting a good signal response during sarcosine testing.

The embodiments of the present disclosure relate to decreasing the bioavailability of one or more target biomolecules by providing a composition that comprises a recombinant plasmid with one or more sequences of micro interfering ribonucleic acid (miRNA). When the recombinant plasmid interacts with a target cell, it causes the target cell to upregulate production of the miRNA, which then decreases the bioavailability of the target biomolecule. In some embodiments of the present disclosure, the target biomolecule is a cytokine or other mediator molecule of an inflammatory response.

Provided are Cas protein-ready tau biosensor cells, CRISPR / Cas synergistic activation mediator (SAM)-ready tau biosensor cells, and methods of preparing and using such cells to screen for tau seeding or aggregation gene modifiers. Also provided are reagents and methods for sensitizing such cells to tau seeding activity or tau aggregation or for causing tau aggregation.

The present invention relates to the field of biotechnology and specifically discloses a method for transforming Rhodosporidium toruloides. The method comprises the following steps: 1) obtaining a single clone of Rhodosporidium toruloides, inoculating it into a culture medium for cultivation, and collecting the cells; 2) adding a transformation solution to the cells in step 1), resuspending the cells, and allowing them to stand; the transformation solution comprises PEG, a mediator, and salmon sperm DNA; 3) adding the DNA to be transformed to the cells in step 2), and incubating the cells; 4) adding a dithiothreitol solution or a dimethyl sulfoxide solution to the cell solution in step 3), followed by heat shock, resuspending the collected cells, and incubating them. The present invention constructs an efficient and reliable method for transforming Rhodosporidium toruloides with exogenous DNA. The transformation method of the present invention for Rhodosporidium toruloides has a simple process and high transformation efficiency, with a maximum transformation efficiency of 1938 transformants / μg DNA.

The present invention relates to IgE epitope-like peptides which have ability to bind to allergen specific IgE paratopes. Said allergen specific IgEs are bound to effector cells of allergic patients. The IgE epitope-like peptides of the invention cover the paratopes of said IgE bound on effector cells, prevent biding of causative allergen on said IgE on effector cells, and thereby prevent degranulation and secretion of mediators of allergic inflammation from effector cells, after contact with the causative allergen. The present invention relates to the methods of using such IgE epitope-like peptides for therapy of allergic reaction. Said allergic reaction is caused by exposure to the causative allergen.

Provided is a second mediator selection method for selecting a second mediator to be used in a method for detecting a target substance present in a solution by means of an electrochemical measurement method, the method making it possible to detect the target substance without inhibiting a reaction for detection.　The second mediator selection method is for selecting a second mediator to be used in a method for detecting a target substance by measuring an electrochemical characteristic of a solution by means of an electrochemical measurement method, the solution containing at least a target substance not fixed to an electrode, a main mediator, and the second mediator, wherein the main mediator performs charge transfer with a working electrode, and the second mediator varies the charge transfer. The selection method includes (i) a step for selecting compounds that interact with the target substance, and (ii) a step for selecting a compound that satisfies a specific charge transfer resistance ratio in the solution.

Disclosed herein are circular RNAs and transfer mediators, as well as related compositions and methods of treatment. The circular RNA may comprise a Group I intron fragment, a spacer region, an IRES, a duplex forming region, and / or an expression sequence, thereby having characteristics of improved expression, functional stability, low immunogenicity, ease of manufacture, and / or prolonged half-life compared to linear RNA. Pharmaceutical compositions comprising such circular RNAs and a transfer vehicle are particularly useful for efficient protein expression in immune cells in vivo. Also disclosed are precursor RNAs and materials that can be used to produce the precursor or circular RNA, which have improved cyclization efficiency and / or are compatible with an effective circular RNA purification process.

The present invention relates to a bio-thiol responsive AIE fluorescent probe and its preparation method and application. Based on the competitive regulation of AuNCs in ZIF-8, the present invention develops a unique "turn-on-turn-off-turn-on" method for highly sensitive and rapid sensing of bio-thiols. Different from traditional AIE, the aggregation-induced emission is regulated and quenched by the pre-embedded competitive factor of Hg<supgt;2+< / supgt; for the development of visual sensing nanoprobes. In the presence of bio-thiols, the mediator of Hg<supgt;2+< / supgt; competes with AuNCs based on the formation of stronger Hg<supgt;2+< / supgt>-S bonds, resulting in the recovery and enhancement of fluorescence. The designed nanoprobe can successfully respond to trace bio-thiols in serum samples. Importantly, compared with free AuNCs, its solid stability retains great potential for the sensing of bio-thiols, which can highly promote the progress of disease diagnosis.

The present invention relates to detection reagents and electrode arrangements for multi-analyte diagnostic test elements and methods of use thereof. Detection reagents, multi-analyte test elements, test systems, and multi-analyte measurement methods are provided. In particular, a multi-analyte test element has (1) a first working electrode and a first counter electrode pair covered with a first analyte-specific reagent comprising an enzyme, a coenzyme and a first medium, and has (2) a second working electrode covered with a second analyte-specific reagent comprising an enzyme, a coenzyme and a second medium, where the second medium is different from the first medium. A single counter electrode may be used as a counter electrode for both first and second analyte measurements at their respective working electrodes. Further, the medium concentration, the measurement range, and the applied potential difference are different for each analyte-specific measurement.

Non-human animal cells and non-human animals comprising CRISPR / Cas synergistic activation mediator system components and methods of making and using such non-human animal cells and non-human animals are provided. Methods are provided for using such non-human animals to increase expression of target genes in vivo and to assess CRISPR / Cas synergistic activation mediator systems for the ability to increase expression of target genes in vivo.