187 results about "Molecular binding" patented technology

Provided herein are methods of performing multiplex detection of ligand binding kinetics. In some embodiments, the methods include contacting ligands with an array of nucleic acid barcoded oscillators disposed on a first surface of a substrate that comprises an electrically conductive coating, applying an AC electric field to the substrate sufficient to induce the nucleic acid barcoded oscillators to oscillate proximal to the first surface of the substrate, and detecting changes in oscillation amplitudes of the nucleic acid barcoded oscillators over a duration to produce sets of ligand binding data. In some embodiments, the methods also include contacting barcode decoding nucleic acids with the array of nucleic acid barcoded oscillators applying an AC electric field to the substrate sufficient to induce the nucleic acid barcoded oscillators to oscillate proximal to the first surface of the substrate, and detecting changes in oscillation amplitudes of the nucleic acid barcoded oscillators over a duration to produce sets of barcode decoding data.

The invention relates to a UCNPs probe-based in-situ dynamic monitoring molecular interaction method, which comprises: S1, providing a UCNPs probe, the core layer of the UCNPs probe being a rare earth up-conversion nanocrystal, the shell layer of the UCNPs probe being an anti-quenching inert material, and the anti-quenching inert material coating the surface of the rare earth up-conversion nanocrystal; the surface of the anti-quenching inert material is modified with ligand molecules, and the ligand molecules are used for being specifically combined with target molecules in a to-be-detected sample; s2, mixing or contacting the UCNPs probe with a to-be-detected sample containing target molecules to construct a to-be-analyzed molecular interaction system; s3, irradiating the molecular interaction system by adopting near-infrared pulse laser, and collecting the change of the fluorescence lifetime tau of the UCNPs along with the time t and the change of the fluorescence intensity I along with the time t in real time to obtain a tau-t curve and an I-t curve; and S4, according to the tau-t curve and the I-t curve, realizing in-situ dynamic monitoring on the molecular interaction state. According to the method, a molecular binding / dissociation event is directly converted into a quantifiable and anti-interference optical signal, and the technical defect that in-situ dynamic monitoring of molecular interaction cannot be achieved in a traditional technology is overcome.

The present disclosure relates to a mammalian cell which is modified to express on the surface of its membrane a binding domain which binds to a target molecule. The disclosure also relates to protein constructs and nucleic acids for producing such modified mammalian cells, and to methods for using the mammalian cells to deliver therapeutic agents to target cells or tissues in vivo.

An iRGD-LAMP2B-EGFP fusion protein mediated exosome surface engineering strategy is adopted, through specific recognition of iRGD peptide and integrin alpha v beta 3, corneal neovascularization core lesion cells are actively targeted, the limitation of off-target toxicity of a traditional delivery system is broken through, and a'accurate focus recognition-efficient homing 'targeted delivery normal form is established. Meanwhile, the screened circular RNA with anti-inflammatory and anti-angiogenesis dual activities is used as a core effector molecule, and in combination with an in-situ loading technology of the circular RNA molecule in an exosome parent cell, stable entrapment and targeted release of a nucleic acid drug in an exosome cavity are realized, and the problems that the nucleic acid drug is easy to degrade and poor in targeting property are solved; and dual guarantee of function specificity and delivery stability is formed. And a synergistic treatment system of a targeting exosome carrier and bifunctional circular RNA is further constructed, active molecules are accurately delivered to focus cells, and an inflammation microenvironment and an angiogenesis pathway are synchronously regulated and controlled.

The invention relates to the technical field of bioinformatics, and discloses an iterative feedback type protein targeting molecule intelligent generation method and device, and the method comprises the steps: obtaining molecular structure data, training based on the molecular structure data to obtain a molecular fragment language model, and the molecular fragment language model is used for predicting subsequent molecular fragments according to an input molecular fragment sequence; obtaining an attribute preference data set, and performing alignment fine tuning on the pre-trained molecular fragment language model based on the attribute preference data set to obtain an attribute preference alignment model; and obtaining target structure information of the target protein, taking the attribute preference alignment model as a strategy network, iteratively generating and evaluating candidate molecules through a tree search algorithm under the constraint of the target structure information until a termination condition is met, and outputting the optimized protein targeting molecules. According to the application, excellent pharmacological properties can be taken into account while the protein targeting molecule binding effect is ensured, and the molecule generation quality can be dynamically optimized.

In one aspect, the disclosure relates to compounds methods for treating or preventing diseases associated with aberrant condensation of a biomolecule in a subject, the method including at least the step of contacting one or more cells in the subject with a fusion protein that includes a J domain protein and a targeting molecule, wherein the targeting molecule binds the biomolecule. In one aspect, the biomolecule can be a target protein that may be mutated and / or include one or more intrinsically disordered regions. In another aspect, the targeting molecule can be a nanobody, but other targeting molecules are also contemplated. In still another aspect, the disclosed method is useful for treating and / or preventing cancers such as blood cancers and non-small cell lung cancer. Also disclosed are methods for disrupting condensates in cell culture.

The present disclosure relates to T-cell receptors (TCRs) that bind to tumor-associated antigens (TAA) for targeting cancer cells, T-cells expressing them, methods for producing them, and methods for treating cancers using them. In particular, the present disclosure relates to TCRs and variants thereof that bind to HLA class I or II molecules with a peptide, such as IGF2BP3-001 having the amino acid sequence KIQEILTQV (SEQ ID NO:1). The present disclosure further relates to peptides, proteins, nucleic acids, and cells for use in immunotherapeutic methods. In particular, the present disclosure relates to cancer immunotherapy.The present disclosure further relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides, which can for example serve as active pharmaceutical ingredients in vaccine compositions that stimulate anti-tumor immune responses or stimulate T-cells ex vivo and deliver them to patients. Peptides bound to major histocompatibility complex (MHC) molecules, or the peptides themselves, can also be targets of antibodies, soluble T-cell J receptors and other binding molecules.

The present invention provides a method for screening for a candidate peptide capable of binding to a target molecule, the method including the steps of: (1) preparing a plurality of nucleic acid display libraries containing a barcoded peptide-nucleic acid complex, wherein the barcoded peptide-nucleic acid complex contains a nucleic acid moiety and a peptide moiety, the nucleic acid moiety contains a barcode sequence and a nucleic acid sequence encoding the peptide, and the plurality of nucleic acid display libraries are nucleic acid display libraries, each of which is independently produced by translation using a cell-free translation system; (2) mixing the plurality of nucleic acid display libraries to prepare a mixed nucleic acid display library; (3) bringing the mixed nucleic acid display library into contact with the target molecule; and (4) amplifying a nucleic acid corresponding to the nucleic acid moiety of the barcoded peptide-nucleic acid complex bound to the target molecule, using a barcode primer.

The present invention relates to a method for using an optionally alkoxylated nitrogen-containing polymer in the capture of carbon dioxide, said optionally alkoxylated nitrogen-containing polymer comprising the following steps: a) a step of reacting (i) a di- or oligoamine (A) with (ii) a crosslinking compound (BC) to provide a nitrogen-containing polymer (NP), wherein the crosslinking compound (BC) is (I) phosgene; or (II) comprises at least two amine-reactive groups (ARG), the crosslinking compound (BC) being capable of binding to the amine groups of at least two di- or oligoamine (A) molecules, the nitrogen-containing polymer (NP) comprising the molecular components of the crosslinking compound (BC) that bind to at least two molecular components of the di- or oligoamine (A), the proportion of the crosslinking compound (BC) molecules bound to at least two di- or oligoamine (A) molecules being the crosslinking factor (BF) of the nitrogen-containing polymer (NP), the crosslinking factor (BF) exceeding 50%, the sum of the primary and secondary amine groups of the nitrogen-containing polymer (NP) being at least 600 mg KOH / g, the number average molecular weight (Mn) of the nitrogen-containing polymer (NP) exceeding 600 g / mol, and b) a step of reacting the nitrogen-containing polymer (NP) with an alkylene oxide (AO), wherein the molar ratio of the alkylene oxide (AO) to the NH functionality of the nitrogen-containing polymer (NP) is 0.25 or less, obtainable by a method comprising. The present invention further relates to a method for capturing carbon dioxide from a gas mixture using an optionally alkoxylated nitrogen-containing polymer.

This application provides a method for screening inhibitors targeting CYP7A1 and their use in the preparation of anti-liver cancer drugs, relating to the field of tumor targeted drug design technology. The method for screening inhibitors targeting CYP7A1 protein includes: using the crystal structure of human cholesterol 7α-hydroxylase as a receptor model, precise docking screening is performed using software to screen drug-like molecules with molecular weights of 250-500 Da and lipid-water partition coefficients of -1 to 5 from a compound database; a graph neural network active learning model is used to predict and rank the protein-small molecule binding affinity of compounds in the database; the ΔG between candidate molecules and CYP7A1 is calculated using molecular mechanics / generalized Born surface area methods, with molecules having ΔG ≤ -40 kcal / mol considered potential inhibitors. The inhibitors of this application do not rely on the enzymatic activity of CYP7A1 to achieve anti-tumor effects and do not significantly affect cholesterol and bile acid metabolism levels.

According to the preparation method for improving the metal / polymer bonding strength, a polar polymer film layer is pre-plated on the metal surface, the prepared polar polymer film layer and the metal surface containing hydroxyl generate intermolecular acting force, polymer entanglement occurs between the prepared polar polymer film layer and a polymer plate in subsequent thermal connection, and finally the metal / polymer interface acting force is enhanced; and the interface heat transfer efficiency is improved, the interface temperature is increased to 378 DEG C from 331 DEG C, and the metal / polymer interface connection area is increased to 224 mm < 2 > from 179 mm < 2 >. The metal / polymer interface bonding strength is improved by enhancing the metal / polymer interface acting force and improving the interface heat conduction efficiency, the film thickness control freedom degree is high, the film with any thickness can be obtained by controlling spin-coating parameters, and the method has the advantages of being easy to prepare, high in processing efficiency, low in economic cost and wide in application range.

The invention discloses a microneedle patch for in-vivo space-time omics analysis and a preparation method and application thereof, and belongs to the technical field of gene detection. Comprising the following steps: performing high-density modification on the surface of the microneedle for molecular binding; preparing a micro-needle base grinding tool for constructing a micro-needle patch; connecting the universal primer probe and the capture primer probe to the bar code probe; the microneedle patch captures to-be-detected molecules in a living body in situ; a probe complementary with the strand displacement region is added, polymeric strand displacement is carried out, and the obtained product can be used for constructing a sequencing library to realize spatial omics analysis of a living sample; the microneedle after strand displacement can be coupled with the bar code probe again to realize reuse of the microneedle for a new round of reaction. According to the method, the analysis of the spatial group in the living body sample is realized at extremely low cost, the operation is simple, the application field is wide, and the method can be used for detecting genomes, transcriptomes, proteomes, epigenomes, metabolomes and the like.

A method for detecting a target of interest in a tissue sample is disclosed. The method includes: a) obtaining or having obtained a tissue sample, the tissue sample comprising DNA, non-RNA molecules, and RNA, the RNA comprising the target of interest; b) permeabilizing the tissue sample; c) substantially degrading DNA in the tissue sample; d) introducing primers or probes specific for the target of interest into the tissue sample, wherein the primers or probes bind to the target of interest; and e) detecting the target of interest in the tissue sample by detecting the primers or probes bound to the target of interest. A method for producing a hydrogel within the tissue sample is also disclosed.

The invention relates to the technical field of active ingredient extraction, and particularly provides an extraction method for classifying and screening active ingredients, raw materials are subjected to low-temperature freeze-drying pretreatment by adopting supercritical CO2, and treatment is performed for 4-6 hours under the conditions of minus 40-minus 20 DEG C and 8-12 MPa, so that the active ingredients are reserved to the greatest extent; through gradient ultrasonic-assisted extraction of ultrapure water, a 50% ethanol solution and a 95% ethanol solution, step-by-step separation of water-soluble, alcohol-soluble and fat-soluble components is realized; carrying out multi-dimensional purification by using a composite chromatographic column containing a 0.2 mu m ceramic membrane layer, a macroporous adsorption resin layer and a sephadex layer; a two-channel biosensor array is adopted to synchronously detect a cell response signal and a molecule binding signal, and components with the activity intensity reaching 80% or above are screened; and finally, carrying out vacuum rotary evaporation concentration and spray drying to obtain a finished product, and completing system purity verification through a high performance liquid chromatography-mass spectrometry technology to form a complete quality control system.

Described herein are interferometric sensors that can be used for biochemical testing. Each interferometric sensor includes an interference layer immobilized along a surface of a monolithic substrate. Analyte binding molecules can be coated along a surface of the interference layer. During biochemical testing, when analyte molecules in a sample bind to the analyte binding molecules, a biological layer will form. The monolithic substrate has a higher refractive index than the interference layer. Furthermore, the interference layer can be designed to have a refractive index that is substantially similar to a refractive index of the biological layer.

The invention discloses a small molecule binding protein design method. The method comprises the following steps: S1, a structure acquisition step: acquiring a compound structure of a target small molecule ligand and protein; s2, a candidate sequence generation step: generating a candidate protein sequence set by adopting a protein generation model and adjusting parameters corresponding to the protein generation model according to the compound structure in the step S1; s3, a primary screening step; compounding the candidate protein sequence set in the step S2 with the small molecule ligand in the step S1, predicting a compound structure I, and screening a potential sequence from the compound structure I; s4, a fine screening stage: compounding the potential sequence screened in the step S3 with the small molecule ligand in the step S1, predicting a compound structure II, and screening a preferred protein sequence I from the compound structure II. Through deep fusion of AI generation and physical screening, a layer-by-layer progressive accurate screening funnel is constructed, and the false positive rate is greatly reduced.

The present invention relates to an activatable transmembrane construct and an activatable degrader comprising the same, the activatable transmembrane construct comprising a cell penetrating portion, a cleavable portion and a shielding portion wherein the cell penetrating portion is selected from: a transmembrane peptide, an oligosaccharide peptide and any combination thereof, and / or the shielding portion is selected from a shielding peptide. The activatable transmembrane construct is connected with a target molecule binding part to form an activatable degradant. After the cleavable part is subjected to enzyme digestion, the cell penetrating part shielded by the shielding part is activated, so that the target molecule binding part connected with the cell penetrating part can be mediated to enter the cell to be degraded. After being connected with the activatable transmembrane construct, either a blocking antibody or a non-blocking antibody can achieve the effects of activating T cells and killing tumor cells, and the activatable transmembrane construct has additional benefits.

This provides machine learning techniques for predicting surface-presented peptides. [Solution] This disclosure provides a method for predicting surface-presented peptides using binding and surface-presentation properties. The method may include accessing a trained machine learning model configured to produce an output indicating the degree to which one or more expression levels and one or more peptide presentation metrics are related according to population-level relationships between expression and presentation. For each peptide in a set of peptides from a tissue sample, a score can be determined using the machine learning model and corresponding genomic and transcriptome data. The score predicts whether the corresponding peptide is a surface-presented peptide that binds to an MHC molecule and is presented on the cell surface.

The application provides a photochemical chemiluminescence detection reagent and a preparation method thereof, and a procalcitonin detection method. The photochemical chemiluminescence detection reagent comprises acceptor microspheres and donor microspheres; wherein the acceptor microspheres are carboxyl-modified acceptor microspheres, and the carboxyl is activated by sulfo-NHS / EDC and coupled with a procalcitonin antibody; and the donor microspheres are carboxyl-modified donor microspheres, and the carboxyl is activated by sulfo-NHS / EDC and coupled with a procalcitonin antibody. The photochemical chemiluminescence detection reagent has higher stability in various environments, can more accurately combine with target molecules, realizes more efficient detection and recognition, and enables the microspheres to more accurately capture and fix the target molecules, so as to perform subsequent luminescence reaction. The detection method has high sensitivity and a wide range, can be used as a detection reagent for diagnosing and identifying infectious diseases of individuals, and has application value.

The invention belongs to the technical field of biological detection, and particularly relates to an escherichia coli non-amplification type rapid detection method based on a deoxyribozyme probe. The method comprises the following steps: detecting Escherichia coli by adopting a fluorescent chip, mixing Escherichia coli lysate and RFD-EC recognition molecules for reaction, dripping into the fluorescent chip for reaction, and detecting the fluorescence intensity after the reaction; the fluorescent chip takes paper as a substrate and is coated with d-DNA, the nucleotide sequence of the d-DNA is shown as SEQ ID NO.3, and the 5'end of the d-DNA is marked with biotin. Fluorescent DNA molecules are enriched through a fluorescent chip micro-fluidic technology, and detection can be completed within 0.5-1 hour without enrichment culture in combination with multi-channel fluorescence detection. The detection lower limit of the method is as low as 100 CFU, and the method has the advantages of rapidness, sensitivity and low cost, is suitable for on-site rapid detection of Escherichia coli in clinical samples and environmental samples, and has important application value in the fields of pollution control and the like.

Methods and compositions are provided to identify oligonucleotides that bind targets of interest. The targets include tissues, cells, circulating biomarkers such as microvesicles, including those derived from various diseases. The oligonucleotides can be used in diagnostic and therapeutic applications.

The invention discloses a high-sensitivity biosensor for enhancing photoelectric response based on multi-exciton effect, which is of a layered stacking structure along the vertical direction and sequentially comprises an ITO (indium tin oxide) conductive glass substrate, an HQ-CdS hierarchical quantum structure homojunction photoelectrode and a 5-HT aptamer modification layer from bottom to top, wherein the HQ-CdS photoelectrode is composed of a B-CdS film and an in-situ grown C-modified CdS two-dimensional nanosheet and forms a homojunction structure, the preparation method of the sensor comprises the steps of preparing the B-CdS photoelectrode through chemical bath deposition and annealing treatment, constructing the HQ-CdS photoelectrode through in-situ photoelectrochemical treatment, and then completing sensor assembly through aptamer fixation and target molecule combination. According to the invention, the multi-exciton effect is used as a core signal amplification strategy, and the problem of insufficient resolution of the existing PEC aptamer sensor is solved.

This radioactively labeled compound is represented by formula (1). In formula (1), M represents a radioactive metal ion. A represents a chelate moiety coordinated to the radioactive metal ion. B represents a first atomic group having a structure in which ethyleneimine is polymerized. C represents a second atomic group having a molecular weight of 5000 or less and capable of binding to a molecule expressed in a tumor cell. The second atomic group preferably includes a linear or cyclic peptide. The second atomic group also preferably includes 1-50 amino acid residues.

The invention discloses an optical fiber-based sodium ion concentration detection method. A used device comprises a broadband light source, a single-mode optical fiber, a polarization controller, a flow cell, a TFBG-SPR sensor and a spectrum analyzer. Firstly, the broadband light source emits light with the wavelength range of 1420-1620 nm, the polarization state of the light is adjusted to a P state through the polarization controller, then the light is input into the TFBG / PVC / NPOE / Sodium ion III / MB ion selective membrane, and finally a spectrum is displayed on the spectrum analyzer. The Sodium ion phore III on the surface of the TFBG can be combined with sodium ion molecules to cause the change of the refractive index, the change is shown as the drifting of a transmission spectrum on a spectrum analyzer, and the rapid, accurate and trace detection of the sodium ion concentration is realized by comparing the relationship between the concentrations of different sodium ion solutions and the drifting of the transmission spectrum. The invention provides a novel method which is simple in structure, high in accuracy and quick in response for sodium ion concentration measurement, and has great application potential.

The present application relates to an Intercellular Adhesion Molecule 2 (ICAM-2) binding polypeptide. This ICAM-2 binding polypeptide comprises a fibronectin type III (FN3) domain having at least one modified loop amino acid sequence and, optionally, a modified beta strand. The one or more modified loop sequences, together with the optional beta strand modifications, enable selective binding to ICAM-2. Also disclosed are conjugates that include the ICAM-2 binding polypeptide, polynucleotides encoding the same, and methods of using these materials for inhibiting transplant organ rejection as well as treatment of hypertension and cancer.

Effectiveness of a neoepitope-based immunotherapeutic composition against a tumor can be increased by predicting the surface presentation of the neoepitope bound to the HLA molecule of the tumor cell. Surface presentation levels of neoepitopes can be predicted by identifying any changes in omics data of the tumor cell that may affect the expression or surface trafficking of the HLA molecule and that may affect binding affinities of neoepitopes to the HLA molecule.

The invention discloses a paper box quality detection system, belongs to the technical field of paper box detection, and solves the problems that in the whole production and manufacturing process of a paper box, time difference and condition dependence exist between the curing process of a starch adhesive and the formation of final bonding strength, so that the bonding part of the paper box seems good when the paper box is off line; however, glue failure occurs only during storage or transportation, namely, the false sticking phenomenon is avoided. Comprising a system control module, a constant current source matrix module, a four-electrode sensing module, a multi-channel signal conditioning module, a digital phase-locked amplification module and a temperature and humidity fusion compensation module. According to the method, the molecular binding state of the adhesive layer is monitored in situ through the four-electrode sensor, the final value of the bonding strength after several hours is predicted within the short time of carton offline by combining the multi-frequency impedance spectroscopy and the curing kinetic model, and interception is triggered immediately when it is detected that the hydrogen bond formation rate is lower than that of prefabrication or water residue exceeds the standard; and the phenomenon that a false adhesion phenomenon cannot be identified due to a time difference formed by apparent curing and real strength is avoided.

The invention relates to a light-activated chemiluminescence detection method and application thereof. The method comprises the following steps: mixing and reacting a to-be-detected sample with acceptor microspheres and donor microsphere reagents to obtain a reaction solution, and adding tool molecules into the reaction solution; wherein the receptor microsphere is coated with two specific binding sites, the first specific binding site is selected from a first biomolecule capable of specifically recognizing and binding a target object to be detected, and the second specific binding site is selected from a first tag molecule capable of being specifically recognized and bound by a tool molecule; each tool molecule can be combined with at least two first tag molecules, and at least two acceptor microspheres are gathered through the combination of the tool molecules and the first tag molecules. According to the technical scheme, the light-activated chemiluminescence detection signal-to-noise ratio is increased by increasing the utilization rate of the singlet oxygen generated by the donor microspheres, the light-activated chemiluminescence detection performance such as the detection sensitivity and the detection result accuracy is improved, and the detection capacity of a low-value sample is improved.

Provided are an apparatus and method for producing synthetic bio-oil that can produce synthetic bio-oil that can be used as various fuels using a simple method. [Solution] A synthetic bio-oil production device 1 is provided with a first micronization section 2 equipped with a first cavitation generating ring 20 that breaks down bio-oil molecules, a second micronization section 3 equipped with a second cavitation generating ring 30 that breaks down water molecules, a mixing section 15 that generates a mixture by mixing the broken down bio-oil, water molecules, ethanol and additives at a predetermined blending ratio, and a heteromolecule binding section 4 equipped with a third cavitation generating ring 40 that causes cavitation and in which the broken down bio-oil, water molecules, ethanol and additives form ester bonds to generate synthetic bio-oil.

The invention discloses a probe set. The probe set comprises a first fusion protein and a second fusion protein, wherein the first fusion protein comprises a nuclear localization sequence and a first protein molecule, and the nuclear localization sequence is connected with the first protein molecule; the second fusion protein comprises a TFEB protein and a second protein molecule, the TFEB protein is connected with the second protein molecule, the second protein molecule is used for being combined with the first protein molecule, and a detectable signal is generated after the first protein molecule and the second protein molecule are combined. The probe set can rapidly, accurately and sensitively detect the TFEB nuclear transfer condition, can be used for high-throughput screening of TFEB regulation and control drugs, and reduces the drug screening cost.