13307 results about "Biophysics" patented technology

The invention discloses an arginine decarboxylase diaA enzyme mutant and application thereof in preparation of butanediamine, and belongs to the field of bioengineering. According to the invention, rational charge overturning transformation is simultaneously carried out on a pentamer meridian oligomeric interface and a dimer latitudinal oligomeric interface, so that stable assembly and efficient catalysis of the decamer under the condition of neutral to alkaline pH (7.0-9.0) are realized. Wherein positive charges are introduced into a meridian interface to weaken electrostatic repulsion, and negative charges are introduced into a latitudinal interface to enhance dimer compactness and substrate transfer efficiency. The specific enzyme activity of the representative double mutant AdiAD110K / H736E at pH 8.0 is about 35 times that of a wild type, and the representative double mutant AdiAD110K / H736E keeps a complete decamer state in a pH range of 7.0-9.0. The yield of butanediamine is up to 145.9 g / L under the whole-cell catalysis of the mutant.

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 discloses a rational copolymerization strategy for improving the stability of an oligomeric structure of acid-induced high-order oligomeric decarboxylase AdiA in a neutral to alkaline environment and application of the rational copolymerization strategy, and belongs to the field of bioengineering. According to the strategy, rational charge overturning transformation is carried out on a pentamer radial oligomeric interface and a dimer weft-wise oligomeric interface at the same time, and stable assembly and efficient catalysis of a decamer under the condition that the pH value is from 7.0 to 9.0 from neutral to alkaline are achieved. Wherein positive charges are introduced into a meridian interface to weaken electrostatic repulsion, and negative charges are introduced into a latitudinal interface to enhance dimer compactness and substrate transfer efficiency. The specific enzyme activity of the representative double mutant AdiAD471K / E467K / H736E is 45.5 times that of a wild type when the pH value is 8.0, and the representative double mutant AdiAD471K / E467K / H736E keeps a complete decamer state when the pH value is 7.0-9.0. The yield of butanediamine is up to 156.5 g / L by using the mutant to catalyze whole cells.

The invention discloses a tumor cholesterol metabolism regulation microneedle patch and a preparation method, the microneedle patch comprises a needle tip and a backing which are connected, the needle tip comprises a needle tip body and nanoparticles loaded on the needle tip body, the nanoparticle is a manganese ion-doped organic metal framework, the outer layer of the manganese ion-doped organic metal framework is modified with a targeting agent, cholesterol oxidase and superoxide dismutase are carried on the manganese ion-doped organic metal framework, the targeting agent can target a CD44 receptor, and the organic metal framework can carry drugs. The targeted drug can enter tumor cells in a targeted mode, superoxide dismutase catalyzes superoxide anions overexpressed in the tumor cells to generate H2O2 and O2, O2 needed by catalysis is provided for cholesterol oxidase, cholesterol at the tumor site is consumed by the cholesterol oxidase, accumulation of 7-DHC is reduced, meanwhile H2O2 can be generated, and the cholesterol oxidase can be used for catalyzing the tumor site. H2O2 is catalyzed by manganese ions through a Fenton-like reaction to generate OH to induce tumor cells to generate ferroptosis, so that ferroptosis-immune synergistic treatment is realized.

Provided are crystalline and amorphous forms of (Compound 1), and pharmaceutically acceptable salts and compositions thereof, as well as the use of such for treating conditions associated with the inhibition of KRAS(G12D).

The present invention provides information comprising at least one GSK-3 activator for use in the prevention and / or treatment of aging and aging-related conditions and diseases by increasing proteasome activity.

The invention provides an implantable nerve probe integrated with a biological protection layer, a preparation method and a system. The nerve probe sequentially comprises a bottom biological protection layer, a bottom flexible substrate layer, a conductive layer, a top flexible substrate layer and a top biological protection layer from bottom to top, the bottom biological protection layer and the top biological protection layer form a biological protection layer located on the outermost periphery of the nerve probe and are used for avoiding erosion of a damp and hot cerebrospinal fluid environment in brain tissue. The integrated biological protection layer located on the outermost periphery of the flexible nerve probe is adopted, corrosion of cerebrospinal fluid to the nerve probe can be inhibited in in-vivo application, the long-term biocompatibility of the flexible nerve probe is effectively improved, the in-vivo long-term service life of the flexible nerve probe is effectively prolonged, and the nerve probe has the advantages of being high in integration level, high in stability and the like; and the requirement of in-vivo long-term effective service of the device can be met.

Provided herein are altered cell lines comprising a suspension cell line adapted from an adherent cell line having a different expression profile from a corresponding non-altered adherent cell line, methods for generating altered cell lines, and methods of characterizing altered expression profiles for a gene, a transcript, or a protein in an altered cell line.

The invention relates to the technical field of biological medicine, in particular to a ferroptosis inhibition type phospholipid-like material and application thereof. The ferroptosis inhibition type phospholipid-like material is one of the following structural general formulas (1)-(5). The biomimetic phospholipid-like ferroptosis inhibitor has a long retention characteristic in main positions (cell membranes, endoplasmic reticulum and other organelle membranes) of cell ferroptosis, so that the ferroptosis inhibition efficiency is remarkably improved. The novel phospholipid-like material not only can be used as an active drug molecule, but also can be used as a pharmaceutic adjuvant for constructing drug delivery carriers such as lipidosome and micelle and implant coatings, and is suitable for various administration routes such as oral administration, injection and local administration. The novel biomimetic ferroptosis inhibitor can efficiently relieve cell ferroptosis and has a wide application prospect in the field of treating or retarding ferroptosis-related diseases.

The invention discloses an antler bone strengthening peptide for promoting bone repair as well as a screening method and application thereof, and belongs to the technical field of traditional Chinese medicinal material polypeptides. And the antler bone strengthening peptide is one of G40, G44 and G45. Grinding and crushing the antler, homogenizing the lysate, performing ultrasonic centrifugation, precipitating protein with methanol, centrifuging and discarding the supernatant; extracting, desalting, and freeze-drying to obtain a antler polypeptide extract; liquid chromatography-mass spectrometry detection, Peaks 8 search software and De Novo method analysis are adopted, according to the conditions that ALC is larger than or equal to 95%, local context is larger than or equal to 95%, Area is larger than or equal to 1000000 and an NCBI database, free polypeptide is obtained through comparison, the biological activity probability, the peptide fragment toxicity and the sensitization of the peptide fragment are predicted, and candidate polypeptide is obtained; synthesizing candidate polypeptides by a solid-phase synthesis method; the influence of the candidate polypeptide on osteoblast proliferation is evaluated, and the antler bone strengthening peptide is screened out. The antler bone strengthening peptide promotes osteoblast proliferation, and reveals a potential bone repair mechanism of the antler bone strengthening peptide.

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 invention discloses an antibody-modified lipid nanoparticle, a preparation method thereof and application of the antibody-modified lipid nanoparticle as a targeting carrier. The invention provides lipid nanoparticles coupled with an antibody and loaded with nucleic acid. The lipid nanoparticles are characterized in that raw materials of the lipid nanoparticles consist of ionizable lipid, phospholipid, steroidal lipid, PEG lipid and PEG-Mal lipid, the PEG lipid is C16-PEG2k, and the PEG-Mal lipid is C16-PEG2k-Mal, and the PEG-Mal lipid is C16-PEG2k-Mal. The method aims at the key scientific problems of low delivery efficiency, insufficient targeting and the like in the field of in-vivo hematopoietic stem / progenitor cell gene therapy at present. The invention develops a lipid nanoparticle delivery system based on antibody modification, provides a modular antibody targeted delivery platform with high universality, and shows huge clinical transformation potential.

The invention discloses a method for detecting the concentration of cyclosporine in blood through fluorescence and electrochemical double signals, and belongs to the technical field of biochemical analysis and medical detection. Aiming at the technical problems of insufficient sensitivity and high false positive rate of traditional single-signal detection of blood concentration of cyclosporine, the method comprises the following steps: activating carboxyl microspheres by a coupling agent, fixing double-stranded DNA (deoxyribonucleic acid) formed by a cyclosporine aptamer and an initiator chain, inducing the initiator to release by using a cyclosporine sample, realizing strand displacement through an A2-PEI composite system, and detecting the blood concentration of cyclosporine by using an A < 2 >-PEI composite system. DNA modified cadmium telluride quantum dots are respectively adopted to detect fluorescence signals, eATRP electrochemical signal amplification is carried out to detect electrochemical signals, concentration values obtained by the two signals are verified, and an average value is taken as a result. The method can accurately capture low-concentration cyclosporine signals in blood, eliminates interference of a single method, is mainly used for accurately monitoring the blood concentration of cyclosporine, and provides a reliable detection means for medication safety and curative effect control of cyclosporine in clinical scenes such as organ transplantation.

The invention relates to a cell collection method capable of simultaneously collecting three cells in a co-culture model, and belongs to the technical field of biology. The invention provides a cell collection method capable of simultaneously collecting three cells in a co-culture model, and the cell collection method comprises the following steps: after a three-cell co-culture model is constructed, taking out a Transwell chamber, retaining cells in the lower chamber, and collecting the cells in the lower chamber; respectively digesting the cells on the two sides of the Transwell cell membrane by using a trypsin solution with the concentration of 0.5 g / 100mL so as to respectively collect the cells on the two sides of the Transwell cell membrane. According to the cell collection method disclosed by the invention, the three cells in the three-cell co-culture model are simultaneously collected in a manner of digesting the cells on the two sides of the Transwell membrane step by step by using pancreatin, so that not only is the cell and consumable cost saved, but also the experimental synchronism of the three cells is ensured, and convenience is provided for optimizing the experimental process.

The invention provides a method for separating extracellular vesicles from a milk source, which comprises the step of adding a dispersing agent before adding a precipitator into the milk source to precipitate casein so as to reduce the wrapping of protein precipitation on the extracellular vesicles and improve the yield of the extracellular vesicles, thereby obtaining a milk source extract rich in the extracellular vesicles.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

This disclosure provides nanoparticle compositions, and use thereof for isolating and measuring proteins, protein degrader action, and cells. The disclosed nanoparticles can be identified by barcodes that reveal the identity of and post translational modifications to the bound protein using image processing techniques described herein.

The invention discloses an RGD-click chemical crosslinking siRNA nano-carrier, a preparation method thereof and application of the nano-carrier in preparation of a medicine for treating secondary thyroidism, and belongs to the technical field of medicines.The nano-carrier is RGD-PEG-PLys (N), and the preparation method of the nano-carrier comprises the steps of synthesis of PLys (ss-DBCO), synthesis of RGD-PEG-PLys (N) and the like. According to the application, the nano-carrier is used for preparing siRNA composite nanoparticles; vascular endothelial targeting (RGD), dynamic stability (click crosslinking) and microenvironment responsiveness (disulfide bond) are organically combined for the first time to achieve mutual synergistic interaction, and the effect ceiling of an existing material is broken through; according to the siRNA composite nanoparticle, the silence effect of the PTH gene as long as 70 days can be achieved through single intravenous injection, the PTH inhibition rate is larger than 85%, the siRNA accumulation amount in parathyroid gland tissue is remarkably increased through RGD targeting (8.6 times that of a non-targeting group), the liver and kidney distribution amount is reduced by 60%, and the system toxicity is controllable.

The disclosure provides, for example, double stranded DNA (dsDNA) molecules comprising one or more chemically modified nucleobases. In some embodiments, the dsDNA molecule is circular and comprises a first strand and a second strand, wherein the first strand comprises one or more chemically modified nucleobases, and the second strand is free of chemically modified nucleobases. In some embodiments, the dsDNA molecule comprises a promoter sequence and an effector sequence that encodes an effector.

The invention provides an enzyme response type supramolecular PDRN-mini ECM liposome and a preparation method and application thereof.The enzyme response type supramolecular PDRN-mini ECM liposome comprises phospholipid, a membrane stabilizer, a supramolecular compound and an emulsifier, a water phase formed by the supramolecular compound and the emulsifier serves as an inner core, and the supramolecular compound is formed by PDRN and mini ECM through intermolecular acting force; the mini ECM is formed by self-assembly of collagen peptide, elastin and hyaluronic acid. The supramolecular PDRN-mini ECM liposome with uniform particle size and good stability is obtained through a microfluidic technology, the process is simple, the controllability is high, and amplification is easy.

The invention relates to ultra-small prussian blue nano-particles (T-USPB-C) carrying tirofian, a preparation method of the nano-particles and application of the nano-particles in preparation of drugs for reducing MVO and MIRI. According to the preparation method, the T-USPB-C is prepared by three steps. The T-USPB-C provided by the invention can carry tirofiban, and has catalase and superoxide dismutase simulated nano-enzyme activity. Moreover, the size of the nano-scale drug is required to reach a nano-scale size, and the drug can be efficiently cleared through kidney excretion, so that the potential long-term toxicity problem is minimized. The ultra-small prussian blue nanoparticle carrying the tirofian has an excellent active oxygen scavenging capability. Microvascular perfusion can be rapidly improved through the antithrombotic effect, then the protection effect is continuously achieved through the anti-oxidation and anti-inflammatory mechanism, and microvascular injury and MIRI are effectively prevented.

The invention belongs to the technical field of cytotoxicity intervention, and particularly relates to application of an iNOS inhibitor in preparation of a medicine for relieving cellular injury caused by toxin combined exposure. KK-1 cells serve as a research model, it is shown for the first time that MC-LR and NaNOS combined contamination can remarkably up-regulate the expression level of iNOS protein, and it is found through tests that Nos2 gene silencing can remarkably relieve tight junction damage and cell apoptosis caused by toxin combined exposure in the KK-1 cells; it is revealed for the first time that iNOS is a core target of toxin combined exposure induced cell tight junction damage and apoptosis, and the blank of toxic mechanism research in toxin combined exposure is filled. The application provides a new direction for a detoxification strategy of environmental toxin combined exposure, provides a theoretical basis for developing an iNOS-targeted inhibitor, and also provides a new target for etiological recognition, early diagnosis and prevention of related diseases caused by environmental toxin combined exposure.

The invention discloses a hydrogel-acellular matrix composite patch containing functionalized extracellular vesicles and a preparation method of the hydrogel-acellular matrix composite patch. The composite patch comprises a hydrogel layer and an acellular pericardium matrix material layer, and an extracellular vesicle-macrophage membrane fusion body (EV-MM) is entrapped in the cross-linked hydrogel. From two aspects of improving the targeting of EVs to the cardiac infarction part and enhancing the retention of the EVs at the cardiac infarction part, the distribution condition of the EVs at the cardiac infarction part is improved, so that the action efficiency of the EVs is improved, and the treatment effect is improved.

The invention belongs to the technical field of medicines, and particularly relates to application of Comput-8 in preparation of a product for relieving or treating retina degeneration induced by blue light damage. It is found for the first time that Compond-8 has a protection effect on retina rod cells and cone cells induced by blue light damage, the cilia length, density and membrane disc thickness of the cone cells and the rod cells can be increased, the thickness of a retina outer nuclear layer can be increased, photoreceptor cell damage caused by blue light exposure can be remarkably improved, and the photoreceptor cell damage can be remarkably reduced. The retina degeneration caused by blue light injury can be relieved or treated, and a new thought and means are provided for treatment of the retina degeneration induced by the blue light injury.

The invention discloses a therapeutic nano-vesicle preparation rich in mitochondrial functional protein, a preparation method of the therapeutic nano-vesicle preparation and application of the therapeutic nano-vesicle preparation in treatment of radioactive skin injury. The preparation method comprises the following steps: culturing, amplifying and cleaning umbilical cord mesenchymal stem cells, dispersing the umbilical cord mesenchymal stem cells in a suspension, mechanically extruding the umbilical cord mesenchymal stem cells into a crude solution through a multistage aperture polycarbonate membrane, and centrifuging, concentrating and purifying the crude solution to obtain the preparation. The preparation has the remarkable advantages that local administration can be realized, inflammation can be quickly inhibited, oxidative stress is reduced, and a repair pathway is activated, so that the preparation is suitable for treating acute radioactive skin injury; the preparation method is easy to standardize and scale, high in stability and convenient for emergency storage and delivery, and avoids the defects of cell therapy; a plurality of targets such as immune inflammation, oxidative stress and the like can be synergistically regulated, the biological effect of hUMSCs is simulated and partially replaced, and the limitation caused by the cell survival rate and the microenvironment dependency is avoided; the key function of hUMSCs is covered in function, and the clinical feasibility, safety and emergency suitability of the application level are higher.

The invention provides a rapid quantitative analysis method for an outer vesicle proteome, and belongs to the technical field of quantitative analysis of the outer vesicle proteome. According to the rapid quantitative analysis method for the outer vesicle proteome, firstly, a high-quality outer vesicle sample is obtained through low-speed centrifugation, ultra-speed centrifugation and membrane filtration; and obtaining proteome data by utilizing two-dimensional electrophoresis and mass spectrometry. Then, a mathematical model equation set is constructed for preliminary analysis, a protein interaction network is optimized through an embedded game optimization index model, and feature extraction and quantitative analysis are conducted through a convolution parameter adaptive function and a residual network deep learning model; finally, a quantitative analysis result containing the protein expression level and the function importance is generated in combination with the multi-dimensional protein expression contribution index, and the technical problem that in the prior art, in the rapid quantitative analysis process of the outer vesicle proteome, the protein component complexity is high, and consequently the quantitative precision is low is solved.

The invention relates to the field of biological cells, and particularly discloses a method for quantitatively analyzing metabolites in biological cells based on a Raman spectrum technology, and the method comprises the following steps: S1, collecting a Raman spectrum data set; s2, metabolite with uniform distribution and metabolite with stable content in the cells to be compared are selected as internal standards; s3, extracting the Raman characteristic peak area of the target object, and performing Raman distribution imaging in the cells according to the Raman characteristic peak area of the target object to obtain Raman imaging pictures of a plurality of substances; s4, performing Raman imaging normalization on the target object; s5, converting the normalized Raman peak intensity of the target object into a thermal image, and presenting Raman signals with different intensities in different colors to obtain an intracellular distribution diagram of each component of the intracellular metabolite; and S6, spatial distribution and quantitative analysis of intracellular metabolites. The method disclosed by the invention has the advantages of in-situ, nondestructive, high speed, quick effect, capability of simultaneously and quantitatively analyzing various metabolites on the subcellular scale and the like.

The invention discloses a mixing device for apoptosis inducer stapharia rugosoannulata water-soluble protein, and relates to the field of water-soluble protein mixing equipment.The mixing device comprises a tank body, a top cover is detachably installed at the top of the tank body, and a feeding pipe and a discharging pipe are arranged at the top and the bottom of the side face of the tank body respectively; a top cover is arranged in the tank body, the bottom of the top cover is rotationally connected with a rotating shaft located in the tank body, a plurality of stirring blades are annularly installed at the bottom of the side face of the rotating shaft at equal intervals, the stirring blades are obliquely arranged, and when the rotating shaft drives the stirring blades to rotate, the stirring blades push liquid around the stirring blades to move downwards; and a support frame is mounted at the bottom of the inner wall of the tank body. According to the mixing equipment for the water-soluble protein of the cell apoptosis inducer, the mixing mode of the water-soluble protein is optimized, so that the water-soluble protein can be converged and mixed for multiple times at different degrees in the mixing process, the influence of reduction of the rotating speed of a stirring paddle can be overcome, and the high-efficiency mixing work of the water-soluble protein is ensured.