45 results about "Lipid oxidation" patented technology

The invention discloses a preparation method of liposome for encapsulating euphausia superba oil, and belongs to the field of euphausia superba oil. Through material selection and hierarchical structure design, starch octenyl succinate, sodium alginate and pea protein are screened as composite wall materials, and the materials can achieve a synergistic effect on the molecule-interface-micro-nano scale to delay lipid oxidation, control the targeted release characteristic of active ingredients and improve the absorption efficiency of fat-soluble ingredients. Moreover, the liposome raw material of the euphausia superba oil is screened, and the liposome with low particle size and high stability is prepared.

The invention provides a method for improving the oxidation resistance of phenylalanine based on N-nicotinoyl modification and application of the method. According to the method, N-nicotinoyl phenylalanine amide with antioxidant activity is obtained through chemical synthesis or enzymatic synthesis, and the antioxidant performance of N-nicotinoyl phenylalanine amide is evaluated by using an ABTS free radical scavenging method. Results show that the N-nicotinoyl phenylalanine amide can delay lipid oxidation in a food system, prolong the shelf life of the product and maintain the nutritional stability; in a cosmetic system, skin oxidative damage can be relieved, skin aging can be delayed, and skin color can be improved. The compound disclosed by the invention can show a remarkable antioxidant effect under the condition of a relatively low addition amount, so that a safe and effective antioxidant is provided for the fields of foods and cosmetics, and the compound has a good application value and a good popularization prospect.

The invention discloses a lipid oxidative metabolism characteristic analysis method and system based on REIMS and LC-MS / MS, and belongs to the technical field of lipid oxidative metabolism detection. In order to solve the detection problems of various oxidized lipids, extremely low content in a biological sample and large metabolic fluctuation, the method provided by the invention optimizes a biological sample pretreatment process, sets accurate REIMS and LC-MS / MS technical parameters, adopts two mass spectrometry technologies for combined detection and adopts an internal standard method for quantification, so that the content of the oxidized lipids in the biological sample is greatly reduced, and the content of the oxidized lipids in the biological sample is greatly reduced. And accurate qualitation and quantification of trace lipid oxidation products in a biological sample are realized. The method has the advantages that the trace lipid oxidation products in the biological sample can be accurately qualitative and quantitative, and reliable data support is provided for mining novel biomarkers.

The invention belongs to the technical field of biology, and particularly relates to application of N-Acetyl-D-Glucosamine as an additive in a boar semen diluent preserved at 17 DEG C. The invention further relates to a preparation method of the N-Acetyl-D-Glucosamine. By adding 2.5 mM of N-Acetyl-D-Glucosamine into the boar semen diluent, the activity and the forward movement proportion of boar sperms can be remarkably improved under the preservation condition of 17 DEG C, and meanwhile, no adverse effect is caused on the lipid oxidation state and acrosome integrity of the boar sperms. The method is easy and convenient to operate, low in cost, suitable for the artificial insemination process of a large-scale pig farm and capable of effectively prolonging the preservation time of the boar semen and improving the breeding efficiency.

The invention discloses a model compound-based lipid oxidation free radical specificity induction and detection method, which comprises the following steps: catalyzing a model compound (cumene / cumene hydroperoxide) or a lipid sample by using iron ions (Fe < 2 + > / Fe < 3 + >) with different valence states, and specifically inducing to generate cumene alkyl free radicals, cumene peroxide free radicals and cumene alkoxy free radicals; the method comprises the following steps: reacting a free radical trapping agent PBN with active free radicals to generate a stable PBN-free radical adduct; the adduct is separated and qualitatively identified by utilizing HPLC-TOF / MS (High Performance Liquid Chromatography-Time of Flight / Mass Spectrometry), and is accurately quantified by HPLC-UV (High The method has the advantages that three key free radicals can be specifically distinguished and quantified, the sensitivity is high, the repeatability is good, the method is suitable for free radical analysis from a model system to a complex grease sample, and a reliable analysis means is provided for research on a lipid oxidation mechanism.

The application provides a method for monitoring lipid oxidation tendency, and belongs to the technical field of fluorescent probe detection. The method utilizes the fluorescence characteristics of a BODIPY molecular probe, and through selecting a molecular probe with a specific structure, directional reaction occurs between the BODIPY molecular probe and oxygen free radicals generated by lipid oxidation at a specific pH value. The conjugated system of the BODIPY molecular probe is destroyed, the half-chlorin structure is broken, and the fluorescence color changes from red to blue-green. According to the change of the fluorescence color before and after the reaction, the visualization monitoring of the lipid oxidation tendency and spatial distribution is realized through fluorescence imaging.

To provide a method for determining odor of fish, especially odor deterioration and lipid oxidation degree of tilapia during cold storage.SOLUTION: The method includes the steps of: killing fresh tilapia, slicing, washing, mixing and grinding the fish meat to obtain raw materials; extracting lipids from the raw materials; dividing the obtained lipids and storing them under low-temperature conditions, and after storage, measuring the lipid oxidation degree and lipid metabolic data of tilapia at different refrigeration times using lipid metabolomics technology; constructing an odor-related lipid metabolic network and analyzing the lipid oxidation degree and metabolic data at different refrigeration times based on the lipid metabolic network to obtain metabolic markers corresponding to multiple lipids; screening the obtained metabolic markers to obtain evaluation metabolic markers; and analyzing the oxidation degree and metabolic status of multiple lipids based on the evaluation metabolic markers corresponding to multiple lipids.SELECTED DRAWING: Figure 1

The invention belongs to the field of food processing, and particularly relates to a processing method of tea-flavored fresh braised chicken capable of prolonging the shelf life and an obtained product. According to the processing method provided by the invention, under the action of the tea polyphenol, on one hand, free radicals in a lipid oxidation chain reaction are competitively removed, grease rancidity and protein oxidative degradation are inhibited, and the rising rate of putrefaction indexes such as volatile basic nitrogen and a peroxide value is reduced; on the other hand, the cell membrane integrity of escherichia coli, staphylococcus aureus and other pathogenic bacteria and molds is destroyed, and metabolism and reproduction are inhibited. After the process is optimized, the shelf life of the Texas braised chicken under the normal-temperature vacuum packaging condition is prolonged to 15-20 days compared with that of the Texas braised chicken in the traditional process, artificially synthesized preservatives do not need to be added in the whole process, and the Texas braised chicken conforms to the natural and healthy food consumption trend.

The invention provides a method for inactivating buckwheat lipoxygenase activity by using superheated steam treatment, which comprises the following steps: S1, shelling treatment: milling and shelling buckwheat seeds to obtain buckwheat core powder; s2, superheated steam treatment: enabling the buckwheat core flour to be in full contact with superheated steam at the temperature of 150-190 DEG C, wherein the treatment time is 3-15 seconds; and S3, collecting and storing: collecting the buckwheat core powder treated in the step S2, cooling to room temperature, and sealing and storing the buckwheat core powder in a self-sealing bag. According to the method, through short-time high-temperature superheated steam treatment, lipid oxidation is inhibited while key deterioration enzyme systems in buckwheat are efficiently inactivated, storage rancidity is remarkably delayed, and the method has the advantages of high efficiency, quality guarantee and industrial applicability.

This invention discloses a method for pretreating camellia seeds using low-temperature plasma, relating to the field of bioengineering technology. The method involves discharging the entire surface of the camellia seed using DBD, JET, DF, or RF at atmospheric pressure, preferably DBD 120kV×1min or RF 3m / min at a distance of 0-3mm for 20 passes. This achieves microporousization of the seed coat and targeted disruption of the cell wall to promote mass transfer. The treatment reduces lipase and lipoxygenase activities by approximately 31.72% and 35.69% (or 29.54%), respectively, and significantly enhances the antioxidant capacity of total phenols and DPPH / ABTS / FRAP in the methanol extract (up to 1.58 times the total phenols). This method simultaneously promotes the release of active ingredients, inhibits lipid oxidation, and improves oil yield and quality under low-temperature, non-thermal conditions, making it suitable for continuous industrial applications.

The invention belongs to the technical field of food processing, and particularly relates to a method for delaying lipid oxidation in the frozen storage process of conditioning meat products. According to the method, the fresh meat product is firstly subjected to vacuum cooking, and then the conditioned meat product subjected to vacuum cooking is placed in a ternary dipping freezing system to be frozen for 1-2 h at the temperature of-30 DEG C to-20 DEG C. The treatment method has the beneficial effects that after the fresh meat product is treated by adopting the method in combination with conditioning and rapid freezing, the lipid oxidation rate of the conditioned meat product is remarkably reduced in the subsequent freezing storage process, meanwhile, the second-stage and third-stage structural stability of protein is higher, and the treatment method provided by the invention has the advantages that the treatment effect is good, and the treatment cost is low. The raw materials are simple and easy to obtain, the treatment cost is low, and the universality is higher.

A polyhydroxyalkanoate (PHA) containing monomer units of 3-hydroxybutyrate for use, by oral administration, in the prevention or treatment of an overweight or obesity condition, or of metabolic dysfunctions related to the condition. A marked effect was observed on the reduction of the body weight, both in the case of a standard diet and in the case of a diet rich in fats, a reduction that can be attributed to an increase in lipid oxidation to the detriment of the deposit of excess lipids, as confirmed by the decrease in the body weight and by analyses of the body composition. A positive effect on the metabolic dysfunctions related to an overweight or obesity condition has also been verified, in particular on dyslipidemias, such as the blood level of low-density lipoproteins (LDL cholesterol) and triglycerides, as well as an improvement in the inflammatory state.

The application discloses a CAR-T cell regulated by an ACSL4 gene and a preparation method and application thereof. The application improves the tolerance of the CAR-T cell to in-vivo lipid oxidation stress by regulating the ACSL4 related lipid metabolism process of the CAR-T cell, thereby prolonging the in-vivo persistence and treatment effect of the CAR-T cell, and provides a new technical scheme for the preparation and optimization of a cell immunotherapy product.

The invention discloses a saussurea involucrata polysaccharide, a nanoemulsion thereof, and a preparation method and application of the saussurea involucrata polysaccharide. The specific method comprises the following steps: firstly, drying and grinding saussurea involucrata peel into powder; selecting bacillus altitudinis cultured to the second generation as a fermentation strain, carrying out inoculation fermentation treatment on the powder, and filtering to obtain supernate; and adding ethanol for alcohol precipitation overnight, centrifuging, performing rotary evaporation, removing protein by a Sevage method, dialyzing, purifying, freeze-drying, and repeating the operation to obtain the product. According to the present invention, the Prunus persica pericarp polysaccharide is extracted and purified, the standardized process is established, the Prunus persica polysaccharide nano-emulsion is prepared, and the high encapsulation efficiency and the stability are achieved by optimizing the surfactant system; according to the invention, the saussurea nipponica polysaccharide and the nanoemulsion thereof are innovatively applied to shrimp coating preservation, and a wax layer barrier is broken through by utilizing the nano-size effect and the interface adaptability of the saussurea nipponica polysaccharide, so that microbial proliferation can be remarkably inhibited, fat oxidation can be reduced, the water binding capacity and sensory quality can be maintained, and the shelf life can be effectively prolonged.

The present invention relates to a composition for regulating hepatic lipid metabolism, comprising Lactiplantibacillus plantarum OPT-A1 strain deposited under accession number KCTC 15555BP, a culture liquid thereof, a cultured product thereof, or a culture lysate thereof. The composition suppresses lipid accumulation and expression of genes related to lipogenesis in hepatocytes, and enhances expression of genes related to lipid oxidation. In addition, the composition inhibits accumulation of triglycerides in hepatocytes and reduces blood triglyceride levels, total cholesterol levels, and liver injury indices. Furthermore, the composition promotes rapid consumption of lipids in hepatocytes and somatic cells through enhancement of muscle mass, and thus can be advantageously used as a raw material for foods, pharmaceuticals, and the like related to alleviation and treatment of various metabolic diseases.

This invention relates to the field of rice flour preparation, specifically to rice flour production. The method involves roasting paddy rice at 120-140°C, followed by hulling to obtain roasted rice. The roasted rice is then pulverized to obtain the rice flour. This invention employs a process of roasting, hulling, and grinding to delay the lipid oxidation and rancidity of rice flour, thus extending its shelf life. Simultaneously, the resulting raw rice flour can be enhanced by high-temperature roasting to produce a unique caramelized aroma from the paddy rice itself. This flavor significantly improves the texture and aroma distinctiveness of the rice flour. Directly roasting the paddy rice simplifies the process, saving processing time, reducing costs, and increasing production efficiency.

The present invention relates to the use of a compound for the preparation of a composition for reversing higher lipid oxidation end products (ALE) and / or higher glycosylation end products (AGE). The compounds are represented by the following formula I, wherein R1, R2, R3 and R4 are as defined in the specification. The invention also relates to a composition for reversing ALE and / or AGE comprising said compound and to a cosmetic process comprising applying an effective amount of said compound to the skin of an organism.

The invention discloses an extraction method of theaflavin-3, 3 '-digallate and application of theaflavin-3, 3'-digallate in preparation of microcapsules and duck meat emulsion sausages, and is characterized in that a theaflavin crude product is added into an acetone solution, separation is performed through Sephadex LH-20 gel chromatographic column chromatography, the acetone solution is used as an eluent for gradient elution, an elution component is collected, and the theaflavin-3, 3 '-digallate is obtained. The preparation method comprises the following steps: dissolving theaflavin-3, 3 '-digallate in water to obtain theaflavin-3, 3'-digallate, further mixing a maltodextrin solution, an Arabic gum solution and a beta-cyclodextrin solution, adding the mixture into the theaflavin-3, 3 '-digallate solution to obtain a mixed solution, stirring, and freeze-drying to obtain the theaflavin-3, 3'-digallate microcapsule. The invention further provides application of the microcapsule in preparation of the duck meat emulsified sausage, and the microcapsule has the advantages that the lipid oxidation effect is remarkably inhibited, the flavor stability and slow release property of the duck meat emulsified sausage are improved, and the functional action time of the duck meat emulsified sausage is prolonged.

This invention discloses a hydrophobic active substance encapsulation formulation, its dry preparation method, and its applications, belonging to the fields of nanoencapsulation, food science, and active delivery technology. Utilizing resonant acoustic mixing technology, under completely dry conditions without organic solvents, hydrophobic active substances are mixed with food-grade protein at a specific mass ratio, and a grinding medium of a specific particle size is added. A single-step processing is performed under low-frequency, high-intensity acceleration to achieve non-covalent intercalation and assembly of the two substances. The formulation exhibits uniform particle size and high encapsulation efficiency, with the active substance completely encapsulated in an amorphous form within the protein matrix. This formulation improves the water dispersibility of the hydrophobic component and its retention rate under conditions such as in vitro digestion, heat treatment, ultraviolet irradiation, and long-term storage. In cell models, this formulation demonstrates excellent antioxidant stress and mitochondrial protection capabilities and can be directly used as a clean-label ingredient in functional baked goods, effectively masking the off-flavor of seafood protein, improving texture, and providing long-term inhibition of lipid oxidation.

The invention discloses a method for improving the fishy smell removal effect of freeze-thawed minced fillet by using a natural deep eutectic solvent, and belongs to the field of food processing. NADES is prepared from citric acid and trehalose according to the molar ratio of 2: 1 and added into mirror carp minced carp (w / w = 4%), and after freeze thawing treatment, the content of volatile compounds with the fishy smell characteristic of the minced carp, such as hexanal, heptanal and nonanal, is remarkably reduced, generation of lipid oxidation secondary products is inhibited, meanwhile, the binding capacity of protein to fishy smell substances is enhanced, and release of the substances is reduced. According to the invention, environment-friendly natural degradable materials are adopted, so that a new idea is provided for development of a novel green fishy smell removing agent while the fishy smell of the frozen and thawed surimi is effectively reduced, and a new insight is provided for flavor preservation of the surimi and more types of muscle foods.

The invention belongs to the technical field of medical biological detection, and provides application of selenoprotein P as a target spot in tumor diagnosis and treatment. The invention specifically provides application of a reagent for detecting the expression level of selenoprotein P in preparation of a tumor diagnosis kit, provides a corresponding detection kit, and further provides application of the reagent as a target spot in preparation of tumor treatment drugs and a corresponding pharmaceutical composition. The invention discloses a key function of the Selenop in interaction of the RTMs and the tumor cells, and the key function is specifically shown as that the Selenop is transferred from the RTMs to the tumor cells, lipid oxidation is inhibited, and the tumor cells are protected from ferroptosis. Based on the discovery, the invention provides an application prospect of Selenop as a tumor treatment target, and provides a potential strategy and method for tumor immunotherapy.

This invention discloses a method for improving the quality of Xuanwei ham and its application, belonging to the field of food processing. The Xuanwei ham prepared by this invention through a combination of staged salting and phased temperature and humidity fermentation with mixed fermentation of two Penicillium species, *Penicillium Rubens* W10-1 and *Penicillium fusiforme* V8, effectively increases the ham's moisture content and water activity, improves its color brightness and redness, significantly reduces lipid oxidation, alters the composition of volatile flavor compounds, enhances characteristic flavors such as fruit, wine, and cream aromas, and inhibits the accumulation of undesirable compounds.

The invention relates to an additive of a diluent for preserving boar semen at 17 DEG C and an application method thereof. Myoinositol with the concentration of 1 mg / mL is added into a boar semen diluent, so that the activity and forward movement proportion of boar sperms under the preservation condition of 17 DEG C can be remarkably improved, and meanwhile, the lipid oxidation state and acrosome integrity of the boar sperms are not influenced. The method is easy and convenient to operate, low in cost, suitable for the large-scale pig farm artificial insemination technology and beneficial to prolonging the pig semen preservation time and improving the breeding efficiency.

The application discloses a method for identifying and evaluating the origin and quality of red-ear sorghum, comprising the following steps: S1, collecting a red-ear sorghum sample to be tested; S2, determining the physicochemical indexes, volatile flavor component spectrum and non-target metabolite spectrum of the sample to obtain multi-dimensional quality data; and S3, comparing and analyzing the multi-dimensional quality data obtained in the step S2 with a standard quality database of red-ear sorghum from different origins to determine the origin and / or quality characteristics of the sample to be tested. It is found that the samples from the core production area in Guizhou are characterized by high tannin content, enrichment of flavonoids and tannin secondary metabolites; the samples from the surrounding production areas in Guizhou are characterized by high starch content, high protein content and active amino acid metabolism; and the samples from the production areas outside Guizhou are characterized by high thousand-grain weight, high ester flavor substances (especially methyl hexanoate) and enrichment of lipid oxidation products.

The invention belongs to the technical field of cosmetics, and particularly relates to a fat-soluble composition containing a sesame seed extract as well as a preparation method and application of the fat-soluble composition. The sesame seed extract is compounded with at least two synergists in the tocopherol, the oryzanol and the rice germ extract, and a complementary synergistic mechanism can be formed among the components, so that the capabilities of scavenging free radicals and inhibiting lipid oxidation of the composition can be remarkably improved; the antioxidant effect of the composition is far better than that of a sesame seed extract or a single synergist which is independently used, the problems that a traditional fat-soluble antioxidant component is single in effect and insufficient in action strength are effectively solved, and more comprehensive oxidation protection is provided for a fat-soluble system; moreover, isosorbide dimethyl ether with a specific content is specifically selected as a solvent, and the dissolution characteristic of the isosorbide dimethyl ether can accurately adapt to the physicochemical properties of the sesame seed extract and the selected synergist, so that all active ingredients are ensured to be completely dissolved in the solvent, the precipitation phenomenon caused by the difference of the solubility of the ingredients is avoided, and the stability of the composition is ensured.

The invention provides an application of a mitochondrial targeting antioxidant in improving muscle lipid oxidation, and belongs to the technical field of meat preservation. According to the invention, the muscle is only soaked in the mitoquinone solution, so that the oxidation of lipid in the muscle can be obviously improved. Meanwhile, the release of mitochondria ROS (reactive oxygen species) can be remarkably inhibited by the treatment of the mitoquinone, the total antioxidant capacity T-AOC of the muscle is improved, the TBARS value of the slaughtered muscle can be remarkably reduced, and the lipid oxidation is remarkably improved; main lipid molecules PE, DG and PC of the mitochondrial membrane can be protected, further mitochondria is protected, the mitochondrial double-layer membrane can still keep a complete structure and a regular shape within a specific storage time, the biological characteristics of the mitochondrial double-layer membrane are guaranteed, bad flavor substances are reduced, myoglobin discoloration is delayed, natural distribution of lipid is reserved, and the mitochondrial membrane has a good application prospect. The method maintains the bright color, delicate tenderness and mellow flavor of meat products, breaks through the limitation of the traditional technology, and provides a new method for meat preservation.

A live tissue storage solution is formed of an aqueous culture medium including additives, inorganic salts and nutrients. The additives preferably include amino acids including but not limited to L-Arg, L-Cys, Gly, L-His, L-Ile, L-Lys, L-Leu, L-Met, L-Phe, L-Ser, L-Try, L-Try, and L-Val. The inorganic salts preferably include calcium chloride, sodium chloride, magnesium sulphate, sodium bicarbonate, sodium phosphate. The nutrients preferably include glucose, choline, folic acid, nicinamide, riboflavin, which are known to maintain cell culture. Examples include Dulbecco's Modified Eagle Medium DMEM or Minimal Essential Medium MEM with or without serum. The culture medium contains additives to reduce, inhibit, or mitigate lipid oxidation, lipotoxicy, lipid-induced responses, and lipid inflammation.

This invention discloses a kelp fucoidan, its preparation method, and its application. The kelp fucoidan includes LF3-1 and / or LF4-1. The main chain of LF3-1 is composed of alternating →3)-α-L-Fucp-(1→ and →3)-β-D-Galp-(1→). The fucose residues on the main chain of LF3-1 are sulfated at the C-4 position or connected to a first branch, which is composed of →4)-α-L-Fucp-(1→. The galactose residues on the main chain of LF3-1 are sulfated at the C-6 position or connected to a second branch, which is composed of →2,3)-β-D-Manp-(1→ and β-D-Galp-(1→). The sulfate content of LF3-1 is 26.3%, and the weight-average molecular weight of LF3-1 is 305. LF4-1 has a molecular weight of 32.7% and a weight-average molecular weight of 182.1 kDa. Its main chain consists of alternating links of →3)-α-L-Fucp-(1→ and →6)-β-D-Galp-(1→). The fucose in the main chain of LF4-1 is sulfated at C-4 or has a third branch, which is composed of →4)-α-L-Fucp-(1→. The galactose in the main chain of LF4-1 is sulfated at C-3 or has a fourth branch, which is composed of →2,4)-β-D-Manp-(1→ and β-D-Galp-(1→). LF4-1 effectively improves blood lipids and insulin resistance, promotes lipid oxidation and glucose metabolism gene expression, and thus plays a role in weight loss and lipid reduction.

The invention relates to a processing method for preparing millet flour with high storage stability, and belongs to the technical field of food processing. The preparation method comprises the following steps: carrying out heat and humidity-microwave synergistic pretreatment, carrying out double-screw extrusion puffing treatment, carrying out double-stage humidity-controlled cooling, properly drying, and carrying out sealed packaging. The raw material millet is subjected to enzyme pre-deactivation in a damp-heat and microwave synergistic manner, so that the lipase activity is effectively reduced; then, a high-temperature short-time double-screw extrusion puffing technology is adopted, enzyme deactivation is further carried out while the millet structure is gelatinized and modified, and the flavor of the product is improved; and the puffed material is subjected to staged humidity-controlled cooling and accurate drying until the water activity is 0.3-0.4, so that the cooperative control of water and lipid oxidation is finally realized, and the storage period of the millet flour is remarkably prolonged. The method is high in process controllability, easy and convenient to operate and suitable for continuous industrial production, and the obtained millet flour has high storage stability and good flavor and nutrition maintaining effects and is suitable for development of products such as meal replacement powder, nutrition powder and infant complementary food.

The invention relates to the technical field of biology, in particular to application of beta-hydroxybutyric acid in metabolic dysfunction related fatty liver diseases. According to the application, the accelerant for promoting the intermediate metabolite beta-hydroxybutyryl coenzyme A of beta-hydroxybutyric acid is used for preparing the medicine for treating the metabolic dysfunction related fatty liver disease. According to the application, based on in-vitro experiments, it is found that the hepatocyte histone beta-hydroxybutyrylation modification level can be up-regulated by improving the concentration of beta-hydroxybutyryl coenzyme A in hepatocytes, and the expression level of PPARalpha in the hepatocytes and lipid oxidation genes regulated and controlled in the downstream of the PPARalpha is promoted; and by inhibiting the synthesis of the beta-hydroxybutyryl coenzyme A in the hepatocytes, the histone beta-hydroxybutyryl modification level in the hepatocytes can be reduced, and the accumulation of lipids in the hepatocytes can be aggravated, so that the blank between the beta-hydroxybutyryl coenzyme A and the metabolic dysfunction related fatty liver diseases in the prior art is filled.