56 results about "Dephosphorylation" patented technology

The invention discloses application of hairyvein agrimony in preparation of a weight-reducing medicine. The weight-losing medicine is a hairyvein agrimony decoction, extract or monomer agrimonin, the effective components in the medicine are agrimonin and derivatives thereof, and STAT3 activity and SOCS3 expression can be inhibited, so that the STAT3-SOCS3 activity is kept in a proper range, and the weight-losing effect is achieved. It is found through experiments that the agrimonin can target SET protein, relieve inhibition of SET on PP2A and promote dephosphorylation of PP2A-mediated STAT3, NF-kB and other signals, so that the activity of the STAT3, the NF-kB and the other signals is inhibited, SOCS3 expression is reduced, and the purpose of weight reduction is achieved. The weight-reducing medicine comprises a hairyvein agrimony decoction, a hairyvein agrimony extract and agrimonin, and human body experiments prove that the hairyvein agrimony decoction and the hairyvein agrimony extract have a remarkable weight-reducing effect.

The invention relates to a process for dephosphorylation of skim milk, ultra-filtered milk (UF milk) or micellar casein isolate (MCI) comprising (i) acidification of a skim milk, UF milk or MCI preferably not lower than pH 6.0, preferably between 6.0 and 6.7, (ii) cooling the acidified skim milk, UF milk or MCI to the temperature between 0° C. and 15° C., (iii) adding gluconate and / or maleate to the cooled skim milk, UF milk or MCI and, (iv) washing the skim milk, UF milk or MCI, to remove phosphorus, thus dephosphorylating the skim milk, UF milk or MCI, preferably to an extent that the total phosphorous content of the skim milk, UF milk or MCI is reduced with at least 20%, preferably 20-40%, more preferably 30-40% compared to the material provided to step (i). The invention also relates to dephosphorylated MPC, MPI or MCI obtainable by the process of the invention, and to a liquid heat-sterilized enteral nutritional composition comprising 2.0-3.0 kcal / ml wherein 16-35 en % is provided by protein, the combination of caloric content and relative protein caloric content selected such that there is 10-18 g / 100 ml protein, preferably 12-18 g / 100 ml protein in the composition, wherein the protein comprises micellar casein (MC), whey protein (WP) and optionally caseinate (CAS), wherein there is at least 70 wt % MC and less than 15 wt % WP, based on total protein content, and wherein the composition has a total amount of phosphorous less than 192 mg / 100 ml and / or 30-80 mg / 100 kcal, preferably at least 30-80 mg / 100 kcal, most preferably less than 192 mg / 100 ml and 30-80 mg / 100 kcal.

The invention belongs to the field of feed protein processing, and particularly relates to a method for improving the bioavailability of animal feed protein through chemical enzymolysis. The method comprises the following steps: mixing a compound protein raw material with water to form a suspension; sodium tripolyphosphate is added for phosphorylation pretreatment, so that protein is subjected to specific modification; after the pH is adjusted to be acidic, pepsase and acid phosphatase are added at the same time for an enzymolysis reaction; and after the reaction is finished, performing enzyme deactivation and drying to obtain the modified feed protein. According to the method, a specific enzyme cutting site is created on a protein molecule through chemical phosphorylation, then directional hydrolysis is achieved through efficient recognition of pepsin on the site, and meanwhile dynamic regulation and control of the hydrolysis process are achieved by means of the dephosphorylation effect of acid phosphatase. The obtained product has the outstanding advantages of high content of small peptides, good digestive absorbability, low bitterness, strong biological activity and the like, and the bioavailability of feed protein is remarkably improved.

This invention discloses a polypeptide that inhibits the desimilarization activity of tau protein and its applications, belonging to the field of biomedical technology. The polypeptide of this invention is tau. 438 The peptide is obtained through endogenous tau protein synthesis. The peptide provided by this invention can inhibit tau protein desimulation and increase tau mimicry, exhibiting high specificity and safely and effectively improving cognitive and memory function in AD model mice.

The invention relates to application of lentinan in preparation of a medicine for enhancing Kukuzhou cell immune function, and belongs to the technical field of immunopharmacology. The invention discloses a mechanism and application of lentinan LNT (Lentinan) based on a TLR2 (Toll-Liver Receptor 2) signal channel for enhancing the immune function of liver cumness cells and promoting lysosome maturation. By constructing an LNT fluorescence labeling system, a Kuptake cell in-vivo tracing model and a TLR2 function intervention model, it is proved that LNT can be directly combined with TLR2 and activate a TLR2 / MyD88 / NF-kappa B signal axis, and therefore the phagocytosis and immune response capacity of Kuptake cells is enhanced. Meanwhile, TLR2 signal-induced reactive oxygen species (ROS) up-regulation can promote TFEB dephosphorylation and nuclear translocation, lysosome maturation is driven, and degradation metabolism of LNT is accelerated. The invention provides a TLR2-based immune enhancement mechanism of the LNT, and provides a theoretical basis and an application basis for developing immunomodulatory targeted drugs.

The present invention relates to a process for the dephosphorylation of skimmed milk, ultra-filtered milk (UF milk) or micellar casein isolate (MCI) comprising (i) acidifying the skimmed milk, UF milk or MCI, preferably not below pH 6.0, preferably between 6.0 and 6.7, (ii) cooling the acidified skimmed milk, UF milk or MCI to a temperature between 0 DEG C and 15 DEG C, (iii) adding gluconate and / or maleate to the cooled skimmed milk, UF milk or MCI, and (iv) washing the skimmed milk, UF milk or MCI to remove phosphorus, thereby dephosphorylating the skimmed milk, UF milk or MCI, preferably to the extent that the total phosphorus content of the skimmed milk, UF milk or MCI is reduced by at least 20%, preferably 20-40%, more preferably 30-40%, compared to the material provided to step (i). The invention also relates to a dephosphorylated MPC, MPI or MCI obtainable by the process of the invention and to a liquid enteral nutritional composition comprising 2.0-3.0 kcal / ml of heat sterilization wherein 16 en%-35 en% is provided by a protein, the combination of the calorie content and the relative protein calorie content being selected such that 10-18 g / 100 ml protein, preferably 12-18 g / 100 ml protein is present in the composition, preferably 12-18 g / 100 ml protein, preferably 12-18 g / 100 ml protein, preferably 12-18 g / 100 ml protein, preferably 12-18 g / 100 ml protein, preferably 12-18 g / 100 ml protein, preferably 12-18 g / 100 ml protein, preferably 12-18 g / 100 ml protein, preferably 12-18 g / 100 ml protein. Wherein the protein comprises micellar casein (MC), whey protein (WP) and optionally caseinate (CAS) wherein at least 70 wt% MC and less than 15 wt% WP are present, based on the total protein content, and wherein the composition has a total amount of phosphorus of less than 192 mg / 100 ml and / or 30-80 mg / 100 kcal, preferably at least 30-80 mg / 100 kcal, most preferably less than 192 mg / 100 ml and 30-80 mg / 100 kcal.

The invention provides a genetically engineered bacterium for efficiently producing pseudouridine and application of the genetically engineered bacterium. The genetically engineered bacterium is based on a high-yield uridylic acid strain E. coli MB219 (the patent application number is 202410153359.6), and the high-efficiency pseudouridine engineering bacterium is constructed through systemic gene modification. The genetically engineered bacterium is characterized in that (1) gene knockout: 10 genes such as pbs1, psuK and the like are knocked out to block a metabolic pathway of byproducts; (2) metabolism regulation: replacing a J23110 strong promoter, and overexpressing zwf / gnd to enhance a phosphopentose pathway; (3) heterologous gene integration: integrating a specific dephosphorylase gene HDHD1, and introducing RjpsuG, NmygdH and thyA to construct a co-expression plasmid pRL06; the fermentation yield of the finally obtained engineering bacterium CY20 (pRL06) reaches 45.3 g / L and is increased by 6 times compared with that of a traditional method, the production efficiency is greatly improved, the product purity is high, and by-products are few.

This invention discloses a tandem-responsive self-assembled molecular probe and its applications. The HPO-CYFF-TPP of this invention is converted to HO-CYFF-TPP under the dephosphorylation of overexpressed ALP, restoring the intramolecular charge transfer effect. It then self-assembles into nanoparticles in situ through π-π stacking, exhibiting fluorescence signal quenching and photoacoustic signal enhancement at low viscosity. Upon laser irradiation, the NPs generate a large amount of singlet oxygen in the mitochondria, thereby achieving efficient photodynamic therapy (PDT) and leading to increased viscosity. At high viscosity, due to the suppression of the distorted intramolecular charge transfer effect of HO-CYFF-TPP, the NPs activate the FL signal with a high signal-to-noise ratio and further enhance the PA signal. Therefore, the HPO-CYFF-TPP of this invention can achieve efficient PDT and enable real-time therapeutic effect assessment through FL / PA signals.

Protein phosphatase 5 (PP5) is a serine / threonine protein phosphatase involved in the maturation and activation of numerous signaling pathways essential for cancer growth. PP5 activity is essential for the survival of clear cell renal cell carcinoma (ccRCC), however the mechanism remains unclear. Data demonstrates that PP5 interacts with caspase-8, FADD, and RIPK1, components of extrinsic apoptotic pathway Complex II. Specifically, PP5 dephosphorylates and inactivates the death effector proteins RIPK1 and FADD, preserving Complex II integrity and regulating extrinsic apoptosis. Protein phosphatases are considered to be ‘undruggable,’ however we have developed a specific inhibitor of PP5 (P-053) that prevents substrate binding to the active site. Encouragingly, PP5 inhibition using P-53 in VHL-null ccRCC robustly induces extrinsic apoptosis. Taken together, the data suggests that PP5 promotes ccRCC survival by suppressing extrinsic apoptosis, and small molecule inhibition of PP5 presents a viable therapeutic strategy for ccRCC.

The application provides a uridine monophosphate specific glycoside hydrolase and application thereof in biosynthetic synthesis of pseudouridine. Nmygdh The function of the gene is verified by in-vitro enzyme activity experiment Nmygdh The recombinant protein has broad-spectrum and high-efficiency catalytic activity, and can efficiently catalyze the hydrolysis of glycosidic bonds in various nucleotides, such as uridine monophosphate (UMP), guanosine monophosphate (GMP), adenosine monophosphate (AMP) and cytidine monophosphate (CMP), and the activity of uridine monophosphate is the strongest. The application uses the protein to efficiently hydrolyze uridine monophosphate to obtain two substrates of pseudouridine, i.e. uracil and 5'-phosphoribose, and realizes the atom-economical and efficient biosynthetic synthesis of pseudouridine by combining the cascade reaction of pseudouridine glycosidase EcPsuG and dephosphorylase EcYjjG.

According to the application of the reagent for detecting the phosphorylation level of the S202 and T205 sites of the MAPT protein in preparation of the renal fibrosis diagnosis product, the function research of the MAPT protein is expanded from the traditional field of glomerular podocytes to renal tubular epithelial cells and the fibrosis pathological process of the renal tubular epithelial cells for the first time, and a brand new direction of the MAPT protein in renal disease research is opened up. Different from the conventional general research means which only depends on overall gene knockout or overexpression, the method provided by the invention realizes accurate analysis of the function of the MAPT key phosphorylation site by using the site-specific mutant. Through a systematic function determination experiment, the invention discloses an anti-intuition biological rule with great theoretical significance: although phosphorylation of the sites S202 and T205 obviously drives the fibrosis process of the renal tubular epithelial cells, the fibrosis phenotype cannot be improved by simulating the dephosphorylation state (S202A / T205A mutant) of the sites.

Various aspects of this disclosure relate to the discoveries that (1) acids can catalyze the spontaneous dephosphorylation of phosphoryloxytryptamines into hydroxytryptamines such as psilocybin into psilocin, and (2) hydroxytryptamines are less stable to spontaneous oxidation than phosphoryloxytryptamines. The salt of a phosphoryloxytryptamine and an anion that is the conjugate base of a weak acid can buffer pH upon dissolution of the salt to inhibit the acid-catalyzed dephosphorylation of the phosphoryloxytryptamine and thereby protect it from spontaneous oxidation. Suitable anions include acetate, bicarbonate, dihydrogen phosphate, aspartate, and glutamate.

The invention provides a preparation method and application of a multi-target enzymatic self-assembly fluorescence activated nanoprobe, and belongs to the field of pharmacy. According to the method, an Fmoc solid-phase peptide synthesis strategy is adopted, an N end is connected with a fluorescence quencher Dabcyl, a C end is marked with fluorescein, a near C end is a self-assembly sequence Y (pY) YG capable of generating self-assembly behavior through dephosphorylation of alkaline phosphatase, and a middle section is a cleavage sequence KGGFLGK capable of being cleaved into a fluorescent'switch 'by cathepsin B; the near N end is a functional polypeptide F-pY-LyP-1 of a targeting sequence CGNKRTRGC or LyP-1 which can be highly combined with a p32 receptor on the surface of a foam cell. The fluorescence activated nanoprobe accurately reaches a plaque part under the synergistic effect of multiple target points and is self-assembled into spherical nanoparticles, so that the aggregation and retention effects of the probe in the plaque are improved, the non-specific signal interference is reduced, and the early atherosclerotic plaque is more accurately identified.

The present invention relates to a cell lysate wherein the lysis buffer comprises magnesium acetate, the phosphorylation inhibitor K3L, the agonist of dephosphorylation GADD34 and a caspase inhibitor for use in, or as, a cell-free system and a method for preparing a cell-free protein synthesis system. Further provided is a method for expressing a protein in the cell-free protein synthesis system, a method for screening for a candidate compound for an effect on a target molecule and a use of the cell-free protein synthesis system. The present invention also provides a kit for the above-mentioned cell-free systems.

The invention relates to a dephosphorylation regulation and control MNAzyme-PER programmable converter used for logic calculation and multifunctional sensing. The MNAzyme-PER programmable converter comprises an MNAzyme-PER programmable converter, according to the invention, upstream primer design and enzyme regulation cascade reaction are integrated to form an MNAzyme-primer exchange reaction platform-Dp-PER based on dephosphorylation regulation. The core innovation lies in that a phosphorylation locking conformation generated by an MNAzyme transduction module shows intrinsic reactivity limiting characteristics different from those of a traditional downstream primer, an amplification module can be limited in an inactivated state, signal leakage is inhibited essentially, and activation of the amplification module is achieved through strategic controllable activation. Under a sequential reaction mechanism, seamless connection between a transduction molecule network and a downstream PER amplification circuit is realized through an exquisite upstream primer probe design. Besides, due to the flexible sequence characteristic of the MNAzyme sensing arm, the Dp-PER is endowed with excellent programmability, and the MNAzyme sensing arm is used as a general converter for responding to any molecule input, so that logic operation (YES / NOT / OR / AND / INHIBT), multi-type biomarker detection (nucleic acid / protease) and nanostructure cascade based on tetrahedral DNA are realized.

This disclosure is in the technical field of synthetic biology and metabolic engineering. More particularly, the disclosure is in the technical field of fermentation of metabolically engineered microorganisms. The disclosure describes engineered microorganisms able to synthesize sialylated compounds via an intracellular biosynthesis route. These microorganisms can dephosphorylate N-acetylglucosamine-6-phopshate to N-acetyl glucosamine and convert the N-acetylglucosamine to N-acetylmannosamine. These microorganisms also have the ability to convert N-acetylmannosamine to N-acetyl-neuraminate. Furthermore, provided is a method for the large scale in vivo synthesis of sialylated compounds, by culturing a microorganism in a culture medium, optionally comprising an exogenous precursor such as, but not limited to lactose, lactoNbiose, N-acetyllactosamine and / or an aglycon, wherein the microorganism intracellularly dephosphorylates N-acetylglucosamine-6-phopshate to N-acetylglucosamine, converts N-acetylglucosamine to N-acetylmannosamine and convert the latter further to N-acetyl-neuraminate.

The application discloses a method for preparing 2'-methoxy-uridine triphosphate, which comprises the following steps: taking 2'-methoxy-uridine acid as a substrate, taking adenosine triphosphate as an initial phosphate donor, constructing a phosphate circulation system, adding an enzyme catalyst, and adopting one-pot enzyme method to perform enzyme catalysis reaction, so as to obtain the end product 2'-methoxy-uridine triphosphate. The phosphate circulation system is composed of adenosine triphosphate, adenosine diphosphate and phosphate compounds. The enzyme catalyst catalyzes the dephosphorylation of the phosphate compounds to provide inorganic phosphate to the adenosine diphosphate, and the adenosine triphosphate is regenerated to realize the circulation energy supply. The method adopts high-activity enzyme combination of specific sources, has high conversion rate of the substrate 2'-methoxy-uridine acid, and has high conversion rate of the final 2'-methoxy-uridine triphosphate up to 92.6%, and has the advantages of high synthesis efficiency, simple steps, green environmental protection and controllable cost.

Micellar solutions comprising isolated non-human beta-casein and isolated non-human kappa-casein and substantially free of alpha S-casein artificial casein micelles, including methods of making the same, methods of coagulating the same, and compositions comprising the same; a method of preparing a curd composition from kappa-casein (whether phosphorylated, dephosphorylated or non-phosphorylated) with or without beta-casein (whether phosphorylated, dephosphorylated or non-phosphorylated) for use in the manufacture of downstream derivative products, such as cheese having functional characteristics comparable to equivalent products produced from milk; casein and protein emulsions of non-animal origin, curd compositions and cheese products and methods of producing the same; and a method of treating non-micellar casein to form a Parefirata style cheese product, such as a mozzarella style cheese product, comprising treating dephosphorylated casein or caseinate with a transglutaminase, in combination with oil or fat to form an emulsion useful for forming a cheese product, and treating non-micellar casein to form a Parefirata style cheese product, such as a mozzarella style cheese product. The cheese products may be processed using an acid-induced or chymosin-induced coagulation, such as acid-induced or chymosin-induced coagulation, and using standard cheese processing steps to produce different styles of cheese products.

The invention discloses a method for improving activity of aspergillus oryzae amylase through CreA C terminal dephosphorylation mutation, and belongs to the technical field of enzyme engineering. According to the method, a CreA dephosphorylation mutant strain is constructed by performing site-specific mutagenesis on a C-terminal phosphorylation site coding gene of an aspergillus oryzae carbon metabolism inhibition core transcription factor CreA, so that a carbon metabolite repression effect is relieved, and the yield of amylase is increased. Specifically, four phosphorylation sites (S414, S415, T416 and S419) at the C tail end of the CreA protein are mutated into valine (V). When the mutant strain is used for fermentation, the expression of amylase can be remarkably improved. Experiments prove that the amylase activity of the mutant strain 4M can be 3 times that of a reference strain after the mutant strain is cultured for 6 days in a culture medium taking starch as a carbon source. The invention provides a new strain modification strategy for efficient production of amylase.

The invention belongs to the field of plant genetic engineering, and particularly relates to a pittosporum tobira SsPOD gene and application thereof in salt-resistant breeding of plants. The nucleotide sequence of the pittosporum tobira SsPOD gene disclosed by the invention is as shown in SEQ ID NO. 1. Experiments show that the salt tolerance can be remarkably improved by overexpressing the gene in arabidopsis thaliana or specifically performing dephosphorylation modification on threonine at the 46th site of the encoded protein of the gene. Specifically, the antioxidant enzyme (POD) activity of the two transgenic plants is enhanced, the accumulation of toxic substances is reduced, and the seed germination rate and the seedling rate under the stress of NaCl are obviously higher than those of a wild control. And a transgenic plant subjected to phosphorylation modification on the site shows different phenotypes. The invention provides a new gene target and a protein modification strategy for molecular breeding of crop salt tolerance.

The invention provides phosphorylation modified and dephosphorylation modified UDP-glycosyl transferase and application thereof, and belongs to the technical field of biology and quantitative phosphorylation proteomics. According to the invention, through early-stage phosphorylation proteomics data analysis and CsUGT84A22 protein sequence analysis in tea trees, phosphorylation modification sites exist in the CsUGT84A22 protein sequence. Protein phosphorylation modification is mostly reported to participate in regulation and control of plant growth and physiological metabolism processes, phosphorylation modified UDP-glycosyltransferase and dephosphorylation modified UDP-glycosyltransferase are provided, and the result shows that the invention discloses the influence of phosphorylation modification on synthesis of tea tree catechin compounds, and the application of the phosphorylation modified UDP-glycosyltransferase in regulation and control of plant growth and physiological metabolism processes is provided. The synthesis route of gallocatechin can be regulated and controlled, and the content of EGCG (epigallocatechin gallate) in tea trees can be changed, so that the bitterness of plants such as the tea trees and the like can be regulated and controlled. And a theoretical foundation is laid for analyzing a regulatory pathway of related phosphorylated protein in a tea tree flavonoid metabolic pathway.

Provided herein are micellar solutions comprising a plurality of artificial casein micelles, wherein the artificial casein micelles comprise; a. one or more α-caseins, and one or more κ-caseins, and are substantially free of β-caseins, wherein the one or more κ-caseins have at least 80% sequence identity to SEQ ID NO: 2, provided the one or more κ-caseins have no more than one cysteine residue; or b. one or more phosphorylated β-caseins, and one or more dephosphorylated β-caseins, and are substantially free of α-caseins and κ-caseins; and methods for producing such micellar solutions, with applicability in the manufacture of substitute dairy products.

The invention discloses a method for preparing 2 '-methoxy-uridine triphosphate, which comprises the following steps: in a liquid reaction system, constructing a phosphoric acid circulating system by taking 2'-methoxy-uridine monophosphate as a substrate and adenosine triphosphate as an initial phosphoric acid donor, adding an enzyme catalyst, and carrying out an enzyme catalysis reaction by adopting a one-pot enzyme method to obtain the 2 '-methoxy-uridine triphosphate. The phosphoric acid circulating system is composed of adenosine triphosphate, adenosine diphosphate and a phosphate compound, inorganic phosphoric acid is provided for adenosine diphosphate by catalyzing dephosphorizing of the phosphate compound through the enzyme catalyst, and adenosine triphosphate is regenerated to achieve circulating energy supply. According to the method, a high-activity enzyme combination with a specific source is adopted, the conversion rate of the substrate 2 '-methoxyl-uridine monophosphate is high, the final conversion rate of 2'-methoxyl-uridine triphosphate reaches up to 92.6%, and the method has the advantages of being high in synthesis efficiency, simple in step, environmentally friendly and controllable in cost.

The invention belongs to the technical field of biology, and particularly discloses a library construction method for combined analysis of histone modification and DNA methylation and application. The method comprises the following steps: assembling fusion transposase with antibody binding activity and a first joint modified by methylated cytosine to obtain a transposase compound, specifically positioning the transposase compound to a target histone modification site for in-situ targeting fragmentation, and introducing the first joint to one end of the obtained DNA fragment; carrying out dephosphorylation and conversion treatment on the DNA fragment with the first linker, introducing a second linker to the other end of the treated DNA fragment, and carrying out amplification to construct a sequencing library; histone modification information and DNA methylation information can be obtained at the same time through sequencing and data analysis. According to the method, information loss caused by DNA degradation can be reduced to the maximum extent, the PCR repetition rate is reduced, high-resolution and multi-dimensional chromatin analysis is achieved with fewer cell samples, and data integrity is improved.

This invention relates to the extraction of psychoactive compounds from fungus for use in medicine. Raw fungus is dried and ground. The solvent used for extraction is methanol or a hydro-methanol mixture, an acidic hydro-methanol mixture, or an alkaline hydro-methanol mixture. The extraction slurry is filtered and pH-adjusted if necessary. The methanol in the solvent is then completely evaporated and water added back, where necessary, to form a concentrated slurry. The concentrated slurry is then standardized to provide a known concentration of the psychoactive alkaloids that have been extracted. The standardized slurry may then be dried to result in a powdered extract with a precisely defined purity of psychoactive compounds.

The invention provides a phosphorylation regulation screening method for kinase recognition and function verification in a plant triterpenoid metabolism regulation path, and belongs to the technical field of plant molecular biology, metabolic engineering and protein function screening. The method comprises the following steps: carrying out PCR site-specific mutagenesis on a conserved Ser / Thr-Pro site of a plant triterpenoid biosynthesis rate-limiting enzyme, and constructing a mutant expression vector simulating phosphorylation and dephosphorylation; co-expressing the mutant and candidate kinase in cells such as plant protoplast and the like; the change of triterpenoid metabolites is detected through gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry, and rapid screening is carried out in combination with luciferase and other reporter gene systems; based on multi-dimensional data integration analysis of metabolite level and fluorescence signals, high-throughput kinase screening and function classification are realized. The method is strong in specificity and high in flux, can accurately analyze a kinase regulation mechanism, provides key technical support for plant triterpenoid metabolism research, agricultural breeding and botanical drug development, and is remarkable in practical value.

The application discloses application of a medicine, miltefosine, in promoting bone formation and preventing and treating osteoporosis. In the bone formation process, the expression of protein phosphatase PPM1A in osteoblasts is significantly increased, the dephosphorylation of a core protein Smad2 of a TGF-beta signal path is regulated, the TGF-beta signal path is inhibited, the expression of an osteogenic marker is promoted, and the osteogenic ability of the organism is enhanced. The application discloses that the medicine, miltefosine, is used as a PPM1A enzyme activity catalyst, the in-vivo intervention of the medicine can significantly accelerate bone repair and delay bone loss of postmenopausal osteoporosis, a mechanism is that the enzyme activity of PPM1A of osteoblasts is catalyzed, the dephosphorylation of Smad2 protein is promoted, the TGF-beta / Smad2 signal path activity is inhibited, bone formation is promoted, bone repair is accelerated, and bone loss is prevented. Therefore, the miltefosine has a good application prospect in clinical treatment of promoting osteogenesis and preventing and treating osteoporosis.

Provided herein are micellar solutions comprising a plurality of artificial casein micelles, wherein the artificial casein micelles comprise; a. one or more α-caseins, and one or more κ-caseins, and are substantially free of β-caseins, wherein the one or more κ-caseins have at least 80% sequence identity to SEQ ID NO: 2, provided the one or more κ-caseins have no more than one cysteine residue; or b. one or more phosphorylated β-caseins, and one or more dephosphorylated β-caseins, and are substantially free of α-caseins and κ-caseins; and methods for producing such micellar solutions, with applicability in the manufacture of substitute dairy products.

The invention discloses an application of FGF12 (Fibroblast Growth Factor 12) in a medicine for improving intrauterine adhesion. A 95% ethanol-induced intrauterine adhesion rat model is constructed, and an adeno-associated virus carrying an FGF12 gene is injected into a uterine cavity for intervention, which indicates that the FGF12 can significantly activate a Rho / ROCK signal channel, further promotes phosphorylation of myosin light chain subunits on myosin light chain phosphatase, inhibits dephosphorylation of MLC, and improves the phosphorylation level of MLC in fibroblasts. The endometrial fibrosis process is inhibited, collagen deposition is remarkably reduced, the endometrial thickness and the gland number are recovered, and the TGF-beta1 expression level is improved. Meanwhile, the pregnancy rate is obviously increased, and the limitation of traditional treatment is broken through.

The present invention relates to a gene construct comprising a nucleotide encoding a decoy peptide that inhibits dephosphorylation of a protein phosphatase 1 (PP1)-mediated phosphoprotein (PLB) and a nucleotide encoding a CCN5 protein or a fragment thereof; the invention also relates to a pharmaceutical composition for preventing and treating heart diseases. The pharmaceutical composition comprises the gene construct. The pharmaceutical composition for preventing and treating heart diseases according to the present invention simultaneously expresses a decoy peptide that inhibits PP1-mediated dephosphorylation and a CCN5 protein, thereby exhibiting a synergistic therapeutic effect, and thus can be effectively used for preventing or treating heart diseases.