22 results about "Small molecule metabolism" patented technology

The application discloses a seminal plasma metabolic biomarker combination for male infertility spermatogenesis obstacle typing diagnosis, and relates to the field of biological science and technology.The application records the metabolic fingerprints of 475 seminal plasma samples by means of nanoparticle-enhanced laser desorption / ionization mass spectrometry, and constructs a seminal plasma metabolic fingerprint database related to spermatogenesis obstacle (SPGF). Then, through machine learning and statistical analysis, six metabolic biomarkers for SPGF typing diagnosis are screened and identified in the seminal plasma, and the six metabolic biomarkers can realize accurate typing of SPGF (AUC=0.814). The application has the advantages of simple sample pretreatment, fast analysis speed and low cost by means of recording the metabolic fingerprints of seminal plasma by means of nanoparticle-enhanced laser desorption / ionization mass spectrometry. Through the synthesized iron oxide nanoparticles as a matrix, small molecule metabolites in the seminal plasma can be efficiently captured and ionized, and complex pretreatment steps such as deproteinization and chromatographic separation are not needed, so that super-fast analysis, super-high sensitivity, extremely low sample consumption and excellent repeatability detection are realized.

The invention provides an iron-based nano material, a preparation method and application, the material comprises magnetic iron oxide nano particles and a functional modification layer on the surface, the magnetic iron oxide nano particles are Fe3O4, the particle size is 10-30 nm, and the magnetic iron oxide nano particles have specific oxygen vacancy concentration, 337 nm laser absorptivity and saturation magnetization; the functional modification layer is an amino-containing polymer layer, such as a polydopamine or cysteine-polyethyleneimine copolymer, and can reduce salt ion interference. The material solves the problems of low molecular weight region background interference, non-uniform crystallization, low ionization efficiency, poor salt tolerance and the like during detection of 100-400Da small molecular metabolites in trace samples such as tears and the like by optimizing magnetic responsiveness, photo-thermal conversion capability and salt resistance of an existing matrix; the method realizes high sensitivity and high repeatability (detection), and is suitable for metabonomics analysis of trace biological samples.

The application discloses that 5-oxoproline can be used as a biomarker for diagnosing chemotherapy-induced cardiomyopathy, and for the first time provides a blood metabolic marker for assisting in predicting and early diagnosing chemotherapy drug-induced cardiomyopathy, which has high accuracy and diagnostic reference value. By accurately determining the content of the small molecule metabolic marker 5-oxoproline in blood, the diagnosis of early myocardial injury induced by chemotherapy drugs will no longer completely rely on conventional non-specific myocardial injury markers and imaging methods, but will rely on the content change of metabolic products in the blood of patients as an objective index, thus advancing the time window for discovering subclinical myocardial injury, significantly improving the early diagnosis detection rate, simplifying the diagnosis process, providing an opportunity for early intervention, helping to prevent or reverse the further aggravation of chemotherapy-induced cardiomyopathy, and thus improving the overall survival prognosis of tumor patients.

The invention relates to a method for screening and identifying metabolites and florae with a human immune regulation effect, which comprises the following steps: (1) establishing immune system humanized mice with multiple intestinal types, and analyzing the change of the florae, the metabolites and the immune system through intestinal flora sequencing, serum metabolome sequencing, flow cytometry and transcriptome sequencing; (2) determining the correlation and sequence between flora related metabolites and the change of the immune system through bioinformatics analysis; and (3) confirming the regulation and control relationship between the candidate metabolites and the immune subgroups in the step (2) through biological experiments. By means of the screening method, the chemical small molecule metabolites for regulating and controlling the human immune cells in the normal physiological state can be screened on a large scale, and the chemical small molecule metabolites can be developed into immunotherapy drugs or used as cell therapy drug culture system components. The screened propionic acid can promote cytotoxicity of T cells and CAR-T and secretion of related cytokines in the aspect of function regulation of the T cells, and the metabolite 2-hydroxybutyric acid is highly positively correlated with the Treg cells and can promote generation and functions of the Treg cells.

This invention provides a strain of *Lactobacillus plantarum*, and discloses the fermentation product of *Eucommia ulmoides* leaves, *Rehmannia glutinosa*, dried ginger, and *Dendrobium officinale* obtained by fermenting these herbs, along with its preparation method and applications. This fermentation product can directionally activate the phenylpropane biosynthetic pathway, inducing the generation of characteristic small molecule metabolites of polyphenols, particularly sanguranyl sulfadiazine (SSA). Moreover, compared to the raw materials, the fermentation product contains more active small molecule metabolites. Finally, experiments on zebrafish modeled with prednisone demonstrated that the fermentation product can significantly promote bone formation. The fermentation product mainly restores the expression levels of related genes to normal zebrafish gene expression levels by regulating these genes. Therefore, the fermentation product can be used to prepare foods or medicines that improve bone health.

The application discloses a plant selenoprotein enzyme peptide composition, effervescent tablets and application thereof, and relates to the field of functional food, and comprises the following components in parts by weight: selenium-rich shepherd's purse powder 5-12 parts; comprehensive fruit and vegetable fermentation powder 8-15 parts; soybean peptide powder 3-10 parts; comprehensive digestive enzyme 05-3 parts; and pharmaceutically or dietetically acceptable excipients; the plant selenoprotein enzyme peptide composition, the effervescent tablets and the application thereof are scientifically combined with organic selenium (selenium-rich shepherd's purse powder), active enzymes and small-molecule metabolites generated by fermentation of various fruits and vegetables, soybean peptides easy to absorb and prebiotics. Selenium is the core of the antioxidant system, peptides and fermentation products provide nutritional substrates and regulatory signals, prebiotics improve the intestinal microenvironment, and multiple components synergistically act on multiple pathways such as immunity and metabolism.

The invention provides a plant lactobacillus, and also discloses a secondary yellow fermented product obtained by fermenting eucommia ulmoides leaves, rehmannia, dried ginger and dendrobium officinale with the plant lactobacillus as well as a preparation method and application of the secondary yellow fermented product. The sec-yellow leavening can directionally activate a phenylpropane biosynthetic pathway and induce the generation of polyphenol characteristic small molecule metabolites, especially the generation of mulberry furan W. The invention also discloses a preparation method of the sec-yellow leavening. And compared with the raw materials, the fermented product has more active small molecule metabolites. Finally, zebra fish experiments after prednisone modeling prove that the sec-yellow yeast can significantly promote osteogenesis. The sec-yellow leavening is recovered to the normal zebrafish gene expression level mainly by regulating the related gene expression level. Therefore, the sec-yellow leavening can be applied to preparation of foods or medicines for improving bone health.

The invention discloses a preparation method of fruit wine, and particularly aims to solve the problem of mutual exclusion of plant lactobacillus and saccharomyces cerevisiae in low-acid fruit juice fermentation. The method adopts the following core processes: (1) strain combination: selecting plant lactobacillus L14 and saccharomyces cerevisiae NX11424 which are proved to be capable of realizing efficient symbiosis with saccharomyces cerevisiae under a physical isolation condition through screening and realizing deep degradation of malic acid and efficient synthesis of lactic acid; (2) physical isolation: separating the double bacteria through a dialysis membrane with the molecular weight cut-off of 10 kDa, blocking the inhibition effect of the yeast on the plant lactobacillus caused by direct contact of thalli, and allowing free exchange of small molecular metabolites such as organic acids and saccharides; (3) synchronously inoculating, namely simultaneously inoculating the two bacteria into low-acid fruit juice (the initial pH is greater than or equal to 4.5, and the total acid is less than or equal to 3g / L), and fermenting at 25 DEG C in a dark place; the antagonism of mixed bacteria fermentation is relieved, high-activity symbiosis of double bacteria is guaranteed, malic acid degradation and lactic acid efficient synthesis are synchronously realized, the acid feeling balance degree of the fruit wine is remarkably improved, and flavor loss is also avoided.

The application discloses a kind of detection techniques of small molecule metabolite based on enhanced multiple alkali metal ion addition technology, it is related to the field of metabolomics, the detection method of small molecule metabolite, including adding alkali metal cation salt solution to the small molecule metabolite to be measured, then using mass spectrum to detect sample.The detection method disclosed in the application can 1) realize multiple alkali metal cation addition of small molecule metabolite significantly enhanced, significantly improve the detection and quantification performance of small molecule metabolite in laser desorption ionization mass spectrometry, improve small molecule metabolite detection capability;2) realize high-throughput and high repeatability detection of small molecule metabolite in biological fluid;3) and by simple comparison multiple alkali metal cation addition, realize isomer differentiation directly in primary mass spectrum.

The application discloses a combined metabolic marker and detection kit for mitochondrial purity evaluation, the marker comprises phosphatidylcholine PC 34:0 (16:0 / 18:0), sphingomyelin SM 34:1;2O (d18:1;2O / 16:0), sphingomyelin SM 44:2;2O (18:1;2O / 24:1) and hexosylceramide HexCer 42:2;2O (d18:1;2O / 24:1), and is used for judging the new application and kit of mitochondrial purity of mitochondria extracted by a mitochondrial extraction method. The application judges the mitochondrial purity extracted by the method by detecting the relative concentrations of four lipid metabolites in the mitochondrial sample, calculating a combined marker variable P based on a binary logistic regression equation and determining a cut-off value. The kit can realize high-sensitivity and high-efficiency detection of the four small molecule metabolites, and has the characteristics of low detection cost and good repeatability.

The invention discloses an application of Danjie emodin in preparation of a product for inhibiting T cell depletion. It is found through in-vitro screening that the Danjie emodin can significantly inhibit T cell depletion. Mechanism research shows that the Danjie emodin does not influence the secretion of Granzyme B and slightly inhibits the secretion level of a cell factor IFN-gamma; by inhibiting an AKT phosphorylation signal channel, accumulation of protein aggregates in T cells is remarkably reduced, and the cell protein homeostasis is maintained, so that T cell depletion is inhibited. Animal experiments also prove that the T cells treated by the Danjie emodin can significantly inhibit the growth of melanoma after adoptive reinfusion. Therefore, the invention provides the application of the Danjie emodin in preparation of the product for inhibiting T cell depletion, and further provides a new small molecule metabolism intervention strategy for improving the solid tumor immunotherapy effect.

The invention relates to the technical field of feed biology, and discloses a straw protein feed based on fungal fermentation and a preparation method thereof. The feed is prepared by taking a modified straw substrate as a main raw material, performing structure modification on natural straw to improve accessibility of cellulose, introducing an organic small molecule metabolism inducer into a fungus fermentation system, matching a nitrogen source, mineral substances and a fermentation regulation and control aid, and performing fermentation under controlled conditions. The small organic molecule metabolism inducer does not serve as a main carbon source in the fermentation process, but can regulate and control nitrogen metabolism and protein synthesis pathways of fungi and promote efficient conversion from a nitrogen source to microbial protein. Compared with the prior art, the method has the advantages that the crude protein content, the protein digestibility and the nitrogen source utilization efficiency of the straw fermented feed can be remarkably improved, high-value utilization of agricultural straw is realized, and the method is suitable for industrial popularization and application of feed.

The application discloses a new method for high-throughput detection of metabolites based on direct injection high-resolution mass spectrometry, and relates to the fields of detection of small molecule metabolites and high-resolution mass spectrometry. The application is based on direct injection high-resolution mass spectrometry technology, and first, a high-coverage and high-quality-accuracy serum metabolite molecular formula database is constructed by using direct injection Fourier transform ion cyclotron resonance ultra-high-resolution mass spectrometry; second, according to the distribution of the number of molecular formulas in different mass-to-charge ratio ranges in the self-built database, a high-throughput metabolome detection method based on direct injection nanoliter spray ionization high-resolution mass spectrometry is established; finally, non-targeted metabolite data obtained by the high-throughput detection method is searched in the self-built database, and high-throughput molecular annotation of metabolites is realized. The application adopts a two-step acquisition strategy, takes a high-reliability and high-coverage metabolome molecular library as a bridge, and takes into account the detection throughput, coverage and reliability. The method has higher reliability, wider metabolome coverage range and is suitable for large-scale metabolome data analysis.

The application belongs to the biological field, and specifically discloses a fish protein fermentation liquid fertilizer rich in dipeptides and small-molecule organic acids and a preparation method. The fish protein liquid fertilizer prepared by the method is rich in active peptides necessary for plant growth and development, including leucine dipeptide, glutamic acid dipeptide and proline dipeptide, and small-molecule organic acids including lactic acid, phenyl lactic acid and gamma-aminobutyric acid. The composition and content of small-molecule metabolites are regulated by controlling the fermentation time, so as to play the regulating function of fish protein leftovers as non-nutritional elements of liquid fertilizer. The application realizes high-value utilization of fishery waste, accurately regulates the content and composition of metabolites of the prepared liquid fertilizer, and the liquid fertilizer can significantly promote the growth of apple trees, improve the soluble solid content and quality of fruits, and has multiple functions of nutrition, soil improvement and stress resistance enhancement.

The invention relates to the technical field of plant tissue culture, and discloses an azalea tissue culture and rapid propagation method which comprises the following steps: S1, preparing an azalea explant and a culture medium; s2, preparing a dynamic purification culture device and sterilizing; s3, inoculation and dynamic purification culture: inoculating the stem segments into a proliferation culture medium in a growth area in a sterile environment; starting dynamic purification; s4, carrying out subculture multiplication; s5, rooting and seedling hardening. By arranging the dynamic purification culture device, small molecule metabolites generated in a growth area can be continuously removed in the rhododendron tissue culture process, dependence on traditional antioxidants is not needed, the competitive effect of the antioxidants and metabolite adsorption materials is avoided, the stable culture environment can be maintained for a long time, inhibition of metabolite accumulation on plant cell metabolism is reduced, and the survival rate of the rhododendron is increased. The survival of explants and the normal differentiation and growth of bud clusters are effectively guaranteed, and the stability of the tissue culture process and the overall quality of seedlings are improved.

The application provides a MetaSPR optical detection sensor for detecting metabolites in human body fluids, and belongs to the technical field of MetaSPR sensors. The MetaSPR optical detection sensor comprises a MetaSPR chip; the application is characterized in that a metal film with a silver mirror effect is deposited on the back of the MetaSPR chip, and a Ti3C2T x The mixed solution of MXene and graphene oxide is dried to obtain the MGMSPR sensor; when the MGMSPR sensor is used for detecting metabolites in human body fluids, corresponding enzymes and protective layers are added first, then the sample to be detected is added, and the corresponding products are detected by an optical or electrochemical method to realize quantitative analysis. The MGMSPR sensor prepared by the application has a unique nanoscale 3D structure on the surface, has higher sensitivity and specificity, and has a lower detection limit compared with traditional MetaSPR sensors, is suitable for detecting lower concentration samples, and has a wide application potential in the field of small molecule metabolites in human body fluids.

The invention belongs to the technical field of detection, and particularly relates to a preparation method of a test sample for detecting arachidonic acid-like isomers based on magnetic beads, a test sample solution adopts a chemical derivatization reagent system, and covalent coupling magnetic beads are successfully used for nucleic acid and protein separation through surface modification. By accurately designing molecular recognition sites, the chromatographic separation resolution (delta R is larger than or equal to 1.5) of isomer metabolites can be remarkably improved, meanwhile, by means of an isotope double-labeling strategy, the detection sensitivity is improved by 10-100 times, the treatment time of a single sample is shortened to be within 30 minutes, and more importantly, by means of construction of a solid-phase reaction system, the detection sensitivity is greatly improved. Controllable optimization of derivatization reaction efficiency is achieved (the reaction conversion rate is larger than 98%), and a key technical foundation is laid for follow-up development of a full-automatic mass spectrum combined detection technology. The magnetic bead mediated solid phase derivatization strategy is expected to renovate the analysis normal form of small molecule metabolites, and promotes the metabonomics research to develop towards high flux and automation.

The invention discloses a compound microbial preparation as well as a preparation method and application thereof, and relates to the technical field of microbial preparations. According to the invention, lactobacillus johnsonii and clostridium butyricum are utilized to prepare a composite microbial agent, and then the composite microbial agent is combined with a red clover extract and a lotus seed pot extract to prepare the composite microbial preparation. Through a multi-target and multi-mechanism synergistic mechanism, intestinal microecology is improved, intestinal internal barrier is strengthened, inflammation and oxidation are resisted, and the effect of improving intestinal health of broilers is achieved. Wherein the red clover extract and the lotus seed pot extract can create an intestinal environment beneficial to colonization of the compound microbial agent, so that the compound microbial agent can better play metabolism and immune regulation roles; metabolite of the compound microbial agent can also convert part of plant components into micromolecular metabolite with higher bioavailability and higher activity, so that the anti-inflammatory and micro-ecological regulation effects are further enhanced.

This invention discloses the application of emodin in the preparation of products that inhibit T cell exhaustion. In vitro screening revealed that emodin significantly inhibits T cell exhaustion. Mechanistic studies showed that emodin does not affect Granzyme B secretion, slightly inhibits the secretion level of the cytokine IFN-γ, and significantly reduces the accumulation of protein aggregates within T cells by inhibiting the AKT phosphorylation signaling pathway, thus maintaining cellular protein homeostasis and inhibiting T cell exhaustion. Animal experiments also confirmed that T cells treated with emodin significantly inhibited melanoma growth after adoptive infusion. Therefore, this invention provides the application of emodin in the preparation of products that inhibit T cell exhaustion, further offering a new small-molecule metabolic intervention strategy for improving the efficacy of immunotherapy for solid tumors.

The invention discloses an FELDI nano-particle chip kit and application thereof in screening metabolic marker combinations, and relates to the technical field of biology. The FELDI nano-particle chip kit comprises a methanol solution and a microarray chip which is pre-coated with iron nano-particles, the kit is used for dewaxing tissue slices, the tissue slices are immersed in a methanol solution and incubated to obtain a sample, and the sample is applied to a microarray chip pre-coated with iron nanoparticles; a colorectal cancer tissue metabolism fingerprint database is constructed, and specific metabolism markers combined with L-cysteine, adipic acid, decanoic acid, azelaic acid, pentadecanoic acid, stearic acid and isolithocholic acid are screened. The invention develops an unmarked iron nanoparticle enhanced laser desorption ionization mass spectrometry technology platform, and the small molecule metabolites can be directly and efficiently captured and ionized from the formalin-fixed paraffin-embedded CRC primary tissue section. And screening out a specific small molecule metabolism marker combination for distinguishing lymphatic metastasis and non-metastasis.

The invention belongs to the technical field of mass spectrum imaging, and particularly relates to a synergistic matrix for mass spectrum imaging and a preparation method and application thereof. The invention provides a proton sponge type MALDI-MSI synergistic matrix formed on the basis of 2-hydrazinoquinoline and alpha-cyano-4-hydroxycinnamic acid, aiming at the problems of non-uniform crystallization, strong background interference, different ionization efficiency and complex matrix interference of a biological sample in the traditional MALDI matrix. The ionization efficiency of various metabolites in mass spectrometry can be remarkably improved by means of the uniform crystal morphology and the auxiliary target analyte desorption / ionization capacity. In the application of mass spectrum imaging, the synergistic matrix not only greatly improves the detection signal intensity, but also improves the spatial reproducibility, and provides an effective solution for synchronous high-sensitivity mass spectrum imaging of multiple types of small molecule metabolites in complex biological samples.

The invention discloses application of a rhizoma coptidis-fructus gardeniae medicine pair in preparation of a medicine for resisting sepsis, a sepsis model is constructed through CLP in an experiment, and after administration intervention of the rhizoma coptidis-fructus gardeniae medicine pair, the death rate of mice with sepsis can be remarkably reduced, and the inflammation and infection conditions of the mice can be reduced. In addition, small molecule metabolites in serum of sepsis mice are analyzed by using a metabonomics technology. Research finds that metabolic pathways such as amino acid metabolism play a key role in the serum metabolism regulation process of the coptis chinensis-gardenia medicine for resisting sepsis, the potential target and mechanism of the medicine for intervening sepsis metabolic disorder are disclosed, and a reference basis is provided for preventing and treating sepsis and screening other medicines for treating sepsis.