104 results about "Phosphatase" patented technology

Disclosed herein are genetically engineered Kluyveromyces sp. cells capable of producing D-allulose. The genetically engineered Kluyveromyces sp. cells comprise an exogenous polynucleotide sequence encoding an allulose-6-phosphate 3-epimerase enzyme at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, at least 99%, or100% identical to at least one of SEQ ID NOs:249-256, 258, and 259; and an exogenous polynucleotide sequence encoding an allulose-6-phosphate phosphatase enzyme at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to at least one of SEQ ID NOs:87, 89, 190, 123, 105, 107, 115, 83, 95, 113, 117, 119, 121, 127, 131, 137, 145, 169, 173, 179, and 183.

The application provides a nanobody targeting human transmembrane activator and calcium modulator and cyclophilin interactor (TACI) and an application thereof, and the antibody is derived from a llama heavy chain antibody variable region. The anti-TACI single-domain antibody NB38 can specifically bind to human TACI with high affinity, can recognize a recombinant TACI protein, can also recognize a TACI with a natural conformation on a cell surface, and can partially block a BAFF / APRIL signal pathway. Based on the nanobody, the application constructs a fusion protein, a chimeric antigen receptor, an effector cell expressing the chimeric antigen receptor, and a double-specific cell linker and other genetically engineered forms. The nanobody can be further extended into a drug coupling form. The product of the application can be used for mediating directional recognition and killing of TACI positive cells, and can be used as a supplement and expansion of BCMA targeted therapy, and provides a new candidate technical scheme for targeted therapy of multiple myeloma and other TACI related diseases.

Disclosed herein are genetically engineered Kluyveromyces marxianus cells capable of producing D-allulose with increased talitol formation. The engineered cell may comprise a genetic modification resulting in overexpression of a native talitol dehydrogenase enzyme; an exogenous polynucleotide sequence encoding an allulose-6-phosphate 3-epimerase enzyme at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to at least one of SEQ ID NOs:249-256, 258, and 259; and an exogenous polynucleotide sequence encoding an allulose-6-phosphate phosphatase enzyme at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to at least one of SEQ ID NOs:87, 89, 190, 123, 105, 107, 115, 83, 95, 113, 117, 119, 121, 127, 131, 137, 145, 169, 173, 179, and 183.

The application provides a skin interstitial fluid miRNA multicolor visualization semi-quantitative detection method, which comprises the following steps: incubating a skin interstitial fluid sample with magnetic nano probes of surface immobilized hairpin probes H1, opening H1 and triggering a subsequent hybridization chain reaction of hairpin probes H2 and H3 in the presence of target miRNA, and constructing a biotin-rich DNA complex on the surface of the magnetic beads; performing enzyme labeling by using an alkaline phosphatase-streptavidin coupling compound, and catalyzing ascorbic acid phosphate to generate ascorbic acid potassium iodate, so that the color of the solution changes, and high-sensitivity detection of the target miRNA is realized. The multicolor visualization detection method can produce near-full-spectrum color changes by combining the gold nano double-cone local surface plasmon resonance property change, and is beneficial to improving the portability of the sensor and the accuracy of the visual analysis.

The application provides a kind of basic phosphatase induced T1 and T2 signal switching response type magnetic resonance imaging contrast agent and its preparation method and application, the response type magnetic resonance imaging contrast agent includes superparamagnetic nanoparticle, and polyethylene glycol phosphoric acid monoester modified to the surface of superparamagnetic nanoparticle;The superparamagnetic nanoparticle includes ferroferric oxide nanoparticle.The contrast agent of the application can realize T1 and T2 signal switching, is used for stem cell osteogenic differentiation monitoring, not only improves the detection sensitivity of magnetic resonance imaging to microstructure and function, also provides new tools and methods for stem cell treatment in biomedical research and clinical practice.

This invention discloses a method for producing high-quality sodium caseinate, belonging to the field of food engineering technology. The method includes enzymatic modification, low-temperature alkali conversion, ceramic membrane microfiltration, ultrafiltration desalting and concentration, homogenized spray drying, and fluidized bed agglomeration granulation. Enzymatic modification uses a complex enzyme of endopeptide and phosphatase to hydrolyze bitter peptides and phytic acid at 45–55℃; low-temperature alkali conversion involves gradient alkali addition at 15–25℃ to avoid thermal damage and Maillard reactions; ultrafiltration employs equal-volume dialysis, with water added until the conductivity is ≤500 μS / cm, desalting and removing small-molecule bitterness; finally, agglomeration granulation is achieved by fluidized bed spraying with 0.1%–0.5% lecithin. This invention completely abandons the acid precipitation-alkali dissolution process, coupling enzymatic modification with all-physical membrane separation and purification to produce sodium caseinate that is white in color, pure in flavor, dissolves rapidly in cold water in ≤30 seconds, has an ash content ≤3.5%, reduces wastewater discharge by more than 90%, is environmentally friendly, and suitable for large-scale production.

The application provides a myo-inositol-3-phosphate synthase mutant, which is obtained by mutating a myo-inositol-3-phosphate synthase with an amino acid sequence as shown in SEQ ID NO: 4 at positions 55, 57 and 273 respectively. The application also provides a preparation method of myo-inositol. The inventors have screened a wild-type myo-inositol-3-phosphate synthase and a myo-inositol monophosphatase with good performance, which can be used in cooperation with a glucan phosphorylase and a glucose phosphate mutase to catalyze starch to generate myo-inositol more efficiently. The myo-inositol-3-phosphate synthase mutant is applied to in-vitro non-fermentation biosynthesis of myo-inositol, combined with myo-inositol monophosphatases E1 and E5, and in a way of feeding whole cells, so that starch can be converted into myo-inositol in a one-pot method, without using NAD + coenzymes, and has a good industrial application prospect.

The present disclosure relates generally to processes for providing compounds that can be used as inhibitors of ectonucleotide pyrophosphatase / phosphodiesterase 1 (ENPP1), which inhibitors can be useful in treating or preventing soft bone diseases, such as hypophosphatasia (HPP).

Bispecific antibody constructs comprising a first binding domain, which binds to human alkaline phosphatase, placental type (ALPP) and / or alkaline phosphatase, germ cell type (ALPPL2), on the surface of a tumor cell and a second binding domain, which binds to human CD3 on the surface of a T cell.

The present invention relates to a novel pyrrole derivative compound or a pharmaceutically acceptable salt thereof. In addition, the present invention relates to a pharmaceutical composition for potassium-competitive inhibition of gastric acid secretion and a pharmaceutical composition for preventing or treating diseases caused by gastric acid secretion disorder, the pharmaceutical composition containing the novel pyrrole derivative compound or a pharmaceutically acceptable salt thereof as an active component. The pyrrole derivative compound or the like according to the present invention is a potassium-competitive acid blocker (PCAB) and has an excellent H+ / K+ adenosine triphosphatase (ATPase) (proton pump) inhibition effect, and is thus widely used as a therapeutic agent for diseases caused by gastric acid secretion disorder.

This specification describes methods for treating cancer using small molecule ectonucleotide pyrophosphatase / phosphodiesterase 1 (ENPP1) inhibitors and additional agents.

This invention relates to the field of chemiluminescence detection technology for in vitro diagnostic reagents, specifically to an S100-β chemiluminescence detection kit and its preparation method. It provides a chemiluminescence detection kit for central nervous system-specific proteins using magnetic microparticles. The kit comprises: S100-β calibrator, S100-β monoclonal antibody conjugated with carboxyl magnetic beads, S100-β monoclonal antibody labeled with alkaline phosphatase, AMPPD chemiluminescence substrate solution acted upon by alkaline phosphatase, and concentrated washing buffer. This kit achieves the following: no sample pretreatment required, easy operation, high automation, high sensitivity, automatic result output in 16 minutes, good stability of calibrator and enzyme label, and low cost. It can meet the clinical needs for auxiliary diagnosis and treatment of acute ischemic brain injury.

Disclosed herein are apyrase inhibitors of Formula (I): (I). Also disclosed herein are methods for using the disclosed inhibitors, including in methods for protecting crops from pests. In one aspect the apyrase inhibitors are useful for enhancing the activity of pesticides for the protection of crops from pathogens and to support crop yield.

The application discloses ZmBTB130 The application discloses application of a gene in regulating crop growth and development under low-phosphorus stress, and belongs to the technical field of genetic engineering. ZmBTB130 The application finds that, under normal phosphorus conditions, the growth difference between the knockout plant and the wild-type corn is not obvious; and under low-phosphorus stress conditions, compared with the wild-type corn, the root length and the plant height of the knockout plant are significantly increased, and the inorganic phosphorus content and the acid phosphatase activity in the body are significantly increased. The application provides a new improvement idea for low-phosphorus tolerance breeding and yield improvement of important food crop corn under the background of global phosphorus resource shortage.

The present application relates to the technical field of biotechnology, and particularly relates to a tagatose-6-phosphate phosphatase mutant and a method for synthesizing tagatose from scratch. The method provided by the present application is a one-pot method for biosynthesizing D-tagatose by using starch or dextrin as a substrate, adopting a multi-enzyme cascade reaction system composed of a tagatose-6-phosphate phosphatase mutant, a glycogen-debranching enzyme, an alpha-glucan phosphorylase, a phosphoglucomutase, a glucose-6-phosphate isomerase, a D-tagatose-6-phosphate-3-epimerase and a 4-alpha-glucan transferase. The method can prepare tagatose from ordinary and inexpensive starting materials (starch or dextrin) at a high yield, improves the overall conversion rate of the system and the final yield of tagatose, provides a new technical approach for realizing low-cost and green production of tagatose, and has the advantages of high yield, low cost and being more suitable for industrial production.

This disclosure relates to the use of glycogen phosphatase B agonists in the treatment of neurodegenerative diseases. Specifically, this disclosure provides the use of glycogen phosphatase B agonists (preferably adenosine monophosphate) in the preparation of medicaments for the prevention or treatment of neurodegenerative diseases. This disclosure demonstrates that glycogen phosphatase B agonists (AMPs) hold promise as a safe and effective treatment option for patients with neurodegenerative diseases.

The application discloses application of AML-12 exosomes in preparation of medicines for treating cholestatic liver injury, relates to the technical field of biological medicine, and discloses application of AML-12 cell-derived exosomes in preparation of medicines for preventing and treating ANIT-induced cholestatic liver injury; the treatment is manifested as reduction of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase levels in serum. The application proves that the AML-12 cell-derived exosomes have a significant treatment effect on ANIT-induced cholestatic liver injury, successfully opens up the application of the biological preparation in a brand-new disease field, and fills the blank of the prior art; through in-vivo experiments, it is proved that AML-12 exosome treatment can significantly reduce liver cell injury markers and alkaline phosphatase, a key index of cholestasis, in serum of ANIT model mice, and improve pathological injury of liver tissue, thereby constituting a complete curative effect evidence chain from function to morphology.

This invention discloses the application of agar-agar polysaccharides in the preparation of products with bone density-improving effects. The agar-agar polysaccharides are obtained from agar-agar as raw material through acid extraction, alcohol precipitation, dialysis, and ion exchange chromatography purification, with a weight-average molecular weight range of 1500-5000 Da. This invention applies agar-agar polysaccharides to the preparation of products with bone density-improving effects, including food, health products, or pharmaceuticals; particularly, it can be used to prepare functional cereal foods. The agar-agar polysaccharides of this invention have an ameliorative effect on bone density loss in a dexamethasone-induced zebrafish osteoporosis model, can enhance the activity of alkaline phosphatase (ALP) in zebrafish, and promote osteoblast differentiation.

The invention provides methods for prognosing an increased risk of early onset preeclampsia (EOPE) in a pregnant subject before the disease onset. The methods comprises quantifying small extracellular vesicles that express pairs of biomarkers selected from CD10, CD63 and placental alkaline phosphatase (PLAP) in a sample obtained from the subject.

The application discloses an enzyme response self-assembly polypeptide modified methacrylating polymer and a preparation method and application thereof, and the enzyme response self-assembly polypeptide modified methacrylating polymer has a structure of formula 1. The application converts an endogenous tissue-specific marker alkaline phosphatase concentration gradient into a dynamic gradient evolution of the mechanical properties of a scaffold. By introducing an enzyme response self-assembly polypeptide into a methacrylating polymer structure, the scaffold is subjected to molecular level dynamic self-assembly under the catalysis of phosphatase, and a continuous mechanical gradient is formed from a cartilage region to a subchondral bone region. The process does not require external intervention and is completely regulated by a local microenvironment, thereby real-time adapting to the dynamic requirements of 'early proliferation-late differentiation' of bone cartilage repair. Compared with the prior art, the application not only breaks through the mismatch between a static gradient and a dynamic microenvironment, but also precisely regulates mechanical signals at a molecular scale, and significantly improves the spatial specificity and time synchronism of stem cell differentiation.

The application discloses an active peptide for promoting bone growth, and a preparation method and application thereof. The active peptide contains amino acid sequences GPAGPLGPV, LGVPLPL, FLPEPPQEE and SFLPEPPQE, and is derived from an enzymatic product of animal bone collagen. The average molecular weight of the enzymatic product is 500-1000 Da, and the mass percentage of components with a molecular weight less than 1000 Da is greater than 60%. The preparation method comprises the following steps: sequentially performing acid treatment, alkali treatment, extraction, filtration and ion exchange on animal bone, and then performing enzymolysis on the animal bone under the action of a protease to obtain an enzymolysis solution, wherein the protease is selected from alkaline protease, trypsin and papain; and the enzymolysis solution is separated and purified, wherein the separation and purification comprises ultrafiltration membrane grading and chromatographic separation, the cut-off molecular weight of the ultrafiltration membrane is 3kDa, and the chromatographic separation comprises gel chromatography and reverse-phase high performance liquid chromatography separation. The low-molecular active peptide obtained by the application can promote the proliferation and / or differentiation of osteoblasts, improve the alkaline phosphatase activity, has a small molecular weight and is easy to be absorbed and utilized by the body, has a wide raw material source, has a simple and controllable preparation process, and has a good application prospect.

The present invention relates to the treatment of neurodegenerative diseases, a group of chronic progressive disorders characterized by the gradual loss of neurons or neuronal function in discrete regions of the central nervous system (CNS). In particular, the present invention relates to alkaline phosphatase (AP) for use in the treatment or prevention of mammals suffering from or at risk of neurodegenerative disorders caused by reduced peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1) activity.

The application discloses application of FTY720 as a PP2A phosphatase activator in preparation of a medicine for treating type I neurofibromatosis. The application first uses FTY720 for treatment of type I neurofibromatosis, and proves that FTY720 significantly inhibits formation of neurofibromas by non-specifically activating PP2A phosphatase. In-vivo experimental results show that FTY720 as a single drug can significantly inhibit tumor growth, and a synergistic effect is presented when FTY720 is combined with a MEK inhibitor, and tumor growth is almost completely inhibited. In-vitro cell experiments show that FTY720 as a single drug or in combination with MEKi treatment can inhibit tumor Schwann cells from forming tumor spheres, inhibit cell proliferation and migration, and induce tumor cell apoptosis. The application overcomes the drug resistance problem existing in the prior art MEK inhibitor, and provides a new treatment strategy for type I neurofibromatosis. FTY720 is an FDA-approved drug, and has good safety and drugability, and has high clinical conversion potential.

The present invention relates to novel compounds, to said compounds for use as a medicine, more in particular for the prevention or treatment of diseases mediated by activity of PTPN2 and / or PTPN1, yet more in particular for the prevention or treatment of cancer or metabolic diseases. The present invention also relates to a method for the prevention or treatment of said diseases comprising the use of the novel compounds. The present invention furthermore relates to pharmaceutical compositions or combination preparations of the novel compounds as well as to said compositions or preparations for use as a medicine, more preferably for the prevention or treatment of diseases mediated by activity of PTPN2 and / or PTPN1, yet more in particular for the prevention or treatment of cancer or metabolic diseases. The present invention also relates to processes for the preparation of said compounds.

The application discloses a pea peptide mixture with calcium binding and osteogenesis promoting effects and application thereof, wherein the pea peptide mixture is derived from protein components in a by-product of pea starch extraction, is obtained through alkaline protease and papain enzymolysis and separation and purification, and is rich in aspartic acid and glutamic acid residues. The pea peptide mixture can effectively bind with calcium ions, the pea peptide mixture can promote calcium ion delivery in osteoblasts, improve alkaline phosphatase activity, and promote osteoblast differentiation, the osteogenesis promoting effect of the pea peptide mixture is related to epidermal growth factor receptor EGFR and downstream PI3K-Akt signal pathway regulation. The pea peptide mixture can improve glucocorticoid-induced zebrafish bone mass reduction, and up-regulate mRNA expression levels of ALP, EGFR, PI3K and Akt and other genes related to osteogenesis. The pea peptide mixture has both functions and nutrition, can be used for preparing products for promoting osteogenesis, improving bone mass, improving bone mass reduction and assisting in improving osteoporosis, and has a wide application prospect in the field of bone health.

This invention discloses a method for constructing an enzyme cascade reactor using phosphorylated SBA-15 as a carrier to catalyze the synthesis of isoprene from mevalonic acid, belonging to the field of biocatalysis and synthetic biology. This method constructs a co-immobilized phosphatase cascade reactor consisting of mevalonate kinase (MVK), phosphate mevalonate kinase (PMK), mevalonate diphosphate decarboxylase (MVD), isopentenyl pyrophosphate isomerase (IDI), and isoprene synthase (ISPS), achieving highly efficient cascade catalysis from mevalonic acid (MVA) to isoprene. By immobilizing the five enzymes on a phosphorylated mesoporous SBA-15 carrier through hydrogen bonding, the stability, reusability, and catalytic efficiency of the enzymes are significantly improved, solving the problems of easy inactivation and difficulty in recovery of free enzymes. Simultaneously, optimized reaction conditions enable efficient, low-cost, and sustainable preparation of isoprene, suitable for the industrial production of bio-based isoprene.

The present invention provides combinations of inhibitors of Ectonucleotide Pyrophosphatase / Phosphodiesterase (ENPP1) with a radiation therapy or a radioligand for the purposes of treating cancer. The invention includes both methods of treatment of cancer with the provided combinations and pharmaceutical compositions comprising such combinations. A preferred ENPP1 inhibitor is SR-8541A; and a preferred radioligand is PluvictoTM.

The application belongs to the field of nanomaterials and biomedicine, and provides a X03 phage-cerium oxide nanoscale enzyme composite treatment platform based on chemical cross-linking of polyethylene glycol, a synergistic treatment platform integrating bactericidal and detoxification functions, namely X03@CeO2, is constructed by covalently coupling phage X03 targeting pseudomonas aeruginosa and CeO2 nanoscale enzyme with phosphatase activity, which solves the problem that antibiotic and phage therapy exacerbate systemic inflammatory storm due to massive release of lipopolysaccharide caused by bacterial lysis when killing multiple drug-resistant gram-negative bacteria. In vitro and in vivo experiments show that the complex can efficiently remove bacteria and biofilm, simultaneously degrade released LPS, significantly inhibit the production of inflammatory factors, active oxygen burst and TLR4 pathway activation, greatly improve the survival rate in a lethal sepsis mouse model and reverse multiple organ damage. The application is suitable for treating sepsis caused by drug-resistant gram-negative bacteria.

The application belongs to the technical field of biological detection, and particularly relates to a detection system of foodborne pathogenic bacteria and application thereof. The detection system of foodborne pathogenic bacteria comprises a composite response material, a hyaluronic acid hydrogel containing L-ascorbic acid-2-phosphoric acid trisodium salt and a bacteriophage; the composite response material comprises ZIF-90 nanoparticles and hyaluronidase and alkaline phosphatase encapsulated in the ZIF-90 nanoparticles. The application constructs a dual-mode paper-based visual detection system based on the combination of specific recognition of a bacteriophage and ZIF-90 response release mechanism, and realizes high-specificity detection of target pathogenic bacteria. Compared with the defects that nucleic acid amplification or immunological methods are difficult to distinguish live bacteria from dead bacteria, the application only produces a signal response to live bacteria that can be infected by a bacteriophage, and significantly improves the authenticity and reliability of detection results.