87 results about "Lentinan" patented technology

The invention provides an influenza vaccine adjuvant based on lentinan as well as a preparation method and application thereof. The active ingredient of the vaccine adjuvant is lentinan, the lentinan is extracted from fresh lentinus edodes through a water extraction and alcohol precipitation method, no additional chemical modification is needed, the vaccine adjuvant can be used for preparing the influenza virus vaccine, and the influenza virus vaccine at least contains one of three inactivated influenza virus antigens, namely H1N1 A, H3N2 A and Victoria B. The invention also provides a vaccine preparation and a preparation method thereof, the vaccine preparation comprises the vaccine adjuvant and an influenza virus vaccine, the content of lentinan in the vaccine preparation is 4 mg / mL, and the vaccine preparation has an immunological enhancement effect.

The invention discloses an insect antibacterial peptide nutrient solution as well as a preparation method and application thereof, and belongs to the technical field of biology. Insect protein (fly maggot powder / hermetia illucens) and plant fiber (bran) are subjected to enzymolysis and then subjected to a pH gradient chelation process (5.0-7.0-8.5), metal ions (Fe < 2 + > / Mn < 2 + > / Zn < 2 + >) are added in stages for chelation, the chelation degree is larger than or equal to 91.4%, lentinan and alginate oligosaccharide are added for synergistic interaction, and finally the insect antibacterial peptide nutrient solution is obtained. Experiments prove that after the insect antibacterial peptide nutrient solution prepared by the invention is used for carrying out root irrigation treatment on plants, tomato yellow leaf curl virus or tomato spotted wilt virus can be remarkably prevented and treated, and the insect antibacterial peptide nutrient solution has high efficiency and persistence and conforms to the development direction of green plant protection.

The invention discloses a porcine circovirus type 2 and haemophilus parasuis bivalent inactivated vaccine and a preparation method thereof. According to the invention, a porcine circovirus strain, a haemophilus parasuis serum type 4 strain and a haemophilus parasuis serum type 5 strain which are epidemic in situ are respectively separated and obtained, and the microbial preservation numbers of the porcine circovirus strain, the haemophilus parasuis serum type 4 strain and the haemophilus parasuis serum type 5 strain are respectively CGMCC (China General Microbiological Culture Collection Center) No.47094, CGMCC No.46698 and The separated strain or bacterial strain is prepared into a bivalent inactivated vaccine, and lentinan is added in the vaccine preparation process to enhance the immune effect; a safety evaluation result shows that local or whole-body adverse reaction caused by the bivalent vaccine does not occur, so that the safety of the bivalent vaccine is good; the immune efficacy evaluation result of the bivalent vaccine shows that the bivalent vaccine can provide complete protection for animals aiming at the in-situ epidemic porcine circovirus, haemophilus parasuis serotype 4 and haemophilus parasuis serotype 5, and has good immune protection efficacy.

The invention provides lactobacillus delbrueckii subsp. Bulgaricus LB047 and application thereof in promoting calcium absorption and enhancing immunity, and belongs to the technical field of microorganisms. The invention provides lactobacillus delbrueckii subsp. Bulgaricus LB047, and the preservation number of the lactobacillus delbrueckii subsp. Bulgaricus LB047 is CGMCC No.30725. The invention further provides a preparation method for preparing mushroom peptide fermentation liquor by utilizing the lactobacillus delbrueckii subsp. Bulgaricus LB047, and application of the prepared mushroom peptide fermentation liquor in promoting calcium absorption and enhancing immunity.

The invention discloses a compound plant extract for relieving heat stress of dairy cows. The compound plant extract is prepared from the following components in parts by weight: 33 parts of radix bupleuri polysaccharide, 28 parts of lentinan, 22 parts of dihydromyricetin and 17 parts of chlorogenic acid. The invention also discloses a preparation method of the compound plant extract for relieving heat stress of dairy cows. According to the compound plant extract for relieving the heat stress of the dairy cow, disclosed by the invention, the radix bupleuri polysaccharide, the lentinan, the dihydromyricetin and the chlorogenic acid in different parts by weight are added, and the compound plant extract is added into a daily basal feed for feeding the dairy cow, so that the rectum temperature of the heat stress dairy cow can be remarkably reduced, the milk yield of the dairy cow is increased, and the immunity and the antioxidant capacity of the dairy cow are improved; therefore, the heat stress reaction of the dairy cow is greatly relieved.

This invention discloses a compound traditional Chinese medicine powder inhaler for respiratory tract infections and its preparation method, relating to the field of pharmaceutical formulation technology. The compound traditional Chinese medicine powder inhaler for respiratory tract infections is composed of polysaccharide composite gel microspheres, forsythia, scutellaria, honeysuckle, and isatis root. The polysaccharide composite gel microspheres are composed of seaweed sulfated polysaccharide, lentinan, calcium chloride, and curcumin. Seaweed sulfated polysaccharide, lentinan, curcumin, and calcium chloride cross-link to form a three-dimensional network spherical structure, improving the particle morphology and flowability of the micropowder. Furthermore, due to its good hygroscopic and moisturizing properties, it competitively reduces the moisture absorption of the micropowder, preventing aggregation and further improving flowability. In addition, the gel microspheres have excellent adhesion, adhering to the infection site after entering the respiratory tract, reducing expulsion losses due to respiration, maintaining an effective drug concentration at the infection site, and improving therapeutic efficacy.

The present invention relates to a highly effective, broad-spectrum anti-plant viral disease pharmaceutical composition and its application. The active ingredients of the anti-plant viral disease pharmaceutical composition include chlorin iron and lentinan; wherein the weight ratio of chlorin iron to lentinan is 1:6000 to 4:1. When a certain concentration of the chlorin iron and lentinan pharmaceutical composition is applied to plants, the two active ingredients exert a synergistic effect, alleviating symptoms of diseased plants, reducing disease indexes, and reducing viral accumulation in the plants. The plant anti-viral disease pharmaceutical composition is a biological agent that is environmentally friendly, safe, and environmentally friendly. It has important application prospects in combating plant viral diseases, preventing and controlling plant diseases caused by plant viruses, and improving plant quality.

The invention discloses a lentinan hydrogel film as well as a preparation method and application thereof, the lentinan hydrogel film comprises the following raw materials: lentinan, polyvinyl alcohol and tannic acid, and the lentinan, the polyvinyl alcohol and the tannic acid are mutually crosslinked. The lentinan hydrogel film is applied to preparation of an antibacterial material, an antioxidant material or a skin defect repair material. The lentinan hydrogel film disclosed by the invention is relatively good in viscosity and mechanical property, has very good biological activity and biocompatibility, and has application values in the aspects of antibiosis, antioxidation and skin defect repair.

The invention relates to the technical field of pesticide preparations, in particular to a preparation method of a propionate and oligosaccharin compounded soluble concentrate, which is realized by the following steps: firstly, preparing a mixed solvent; performing ultrasonic and nanometer grinding treatment on the propionate raw medicine, and dissolving the propionate raw medicine in the mixed solvent to obtain a propionate solution; then adding an oligosaccharin combination, and carrying out gradient stirring to obtain a compound stock solution; then, lentinan, a surfactant, a compound stabilizer and other assistants are sequentially added, secondary filtration is performed, and finally the volume is fixed to obtain a finished product. The problems that an existing compound preparation is poor in lipid-water compatibility, insufficient in extreme environment stability and weak in crop stress resistance adaptation are solved, synergism of antifungal, antiviral, cold-resistant, lodging-resistant and quality-improving and yield-increasing is achieved, the compound preparation is particularly suitable for crops such as rice and tobacco in cold regions, the process is compatible with an existing production line, and the compound preparation has wide application prospects.

The invention discloses a mixed suspended seed coating agent for preventing diseases and insect pests in a peanut seedling stage, relates to the technical field of peanut suspended seed coating agents, and aims to solve the technical problems that pungent peculiar smell exists, the insecticidal effect is not comprehensive, the effect of improving soil is not achieved, and rooting and germination of peanuts are not facilitated in the prior art. The mixed suspended seed coating comprises the following components in parts by weight: 10-20 parts of fluopyram, 5-8 parts of a fludioxonil suspending agent, 10-20 parts of difenoconazole, 10-20 parts of trifloxystrobin, 3-5 parts of a plant growth regulator, 3-5 parts of trace elements, 5-10 parts of jatropha curcas biodiesel, 30-45 parts of water, 1-5 parts of an auxiliary agent, 1-3 parts of amino-oligosaccharin, 1-3 parts of lentinan and 1-3 parts of harpin protein. According to the mixed suspended seed coating, 1-3 parts of thiophanate methyl, 1-3 parts of sophocarpidine, 1-3 parts of phoxim, 3-5 parts of herba portulacae, 3-5 parts of tobacco shreds, 3-5 parts of sasangua cake and 3-5 parts of dye are included, the pungent peculiar smell can be reduced, various pests can be effectively killed, and meanwhile the sasangua cake can improve the soil structure.

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.

This invention provides a drug for antagonizing bacterial endotoxins, its preparation method, and its application, belonging to the biomedical field. The composition consists of 25-55 parts of dried powdered traditional Chinese medicine extract, 25-70 parts of mixed essential oil powder, and 40-90 parts of lentinan powder. The traditional Chinese medicine extract is prepared by decoction of Scutellaria baicalensis, Lonicera japonica, Forsythia suspensa, and Isatis indigotica under reduced pressure at low temperature and spray drying. The mixed essential oil powder is prepared by encapsulating peppermint oil and eucalyptus oil with gelatin and hydroxypropyl cellulose and then spray drying under high pressure. This invention, through specific formulation and processing, significantly enhances the synergistic antagonistic effect of each component against endotoxins. Experiments show that this composition exhibits antagonistic activity far superior to ibuprofen in vitro; in vivo, it significantly reduces the endotoxin content in the plasma of 817 broiler chickens, rapidly alleviates LPS-induced fever and diarrhea, and improves decreased growth performance. Therefore, this invention is of great significance for reducing antibiotic dependence and improving the efficiency of livestock and poultry farming.

The utility model discloses a separating device for extracting selenium polysaccharide from selenium-rich mushroom, which relates to the technical field of material separating equipment, and comprises an extraction tank, an alcohol precipitation tank, a Sevage method deproteinization tank and a decoloring tank, the extraction tank is communicated and connected with the alcohol precipitation tank through an extraction liquid conveying pipeline, the alcohol precipitation tank is communicated and connected with the Sevage method deproteinization tank through an alcohol precipitation liquid conveying pipeline, and the decoloring tank is communicated and connected with the Sevage method deproteinization tank through an alcohol precipitation liquid conveying pipeline. The Sevage method deproteinization tank is communicated and connected with the secondary alcohol precipitation tank through a deproteinization liquid pipeline, the secondary alcohol precipitation tank is communicated and connected with the decoloration tank through a secondary alcohol precipitation liquid pipeline, the decoloration tank is communicated and connected with the concentration tank through a decoloration liquid pipeline, the concentration tank is communicated and connected with the reverse osmosis assembly through a concentration liquid pipeline, and the reverse osmosis assembly is communicated and connected with the deproteinization liquid pipeline. According to the utility model, a multi-stage separation method is adopted, the separation purity is high, and the device is practical, reliable, easy to control and suitable for popularization.

The application provides a lactobacillus delbrueckii subsp bulgaricus LB047 and application thereof in promoting calcium absorption and enhancing immunity, and belongs to the technical field of microorganisms.The application provides the lactobacillus delbrueckii subsp bulgaricus LB047, and the preservation number is CGMCC No.30725.The application further provides a preparation method of a lentinan peptide fermentation liquor prepared by using the lactobacillus delbrueckii subsp bulgaricus LB047, and application of the prepared lentinan peptide fermentation liquor in promoting calcium absorption and enhancing immunity.

The invention provides a method for improving tobacco leaf quality in a tobacco leaf mature period, which comprises the following steps: (1) topping in a tobacco plant squaring period, smearing a regulation and control liquid on main veins of upper tobacco leaves 2-3 days after topping, and smearing a regulation and control liquid on one end, close to stalks, of main veins of lower tobacco leaves, the regulation and control liquid at least comprising ferulic acid with the concentration of 10-30 ppm; (2) after the regulation and control liquid is smeared, promoting liquid is sprayed to the whole tobacco plant 2-3 days later, and the promoting liquid is composed of soybean peptides, algal polysaccharides and lentinan. By regulating and controlling the content of chlorogenic acid in the mature period of the tobacco leaves, the irritation of the tobacco leaves to sense organs is reduced, and therefore the quality of the tobacco leaves is improved.

The invention belongs to the technical field of biomedicine, and discloses application of lentinan in preparation of a medicine for treating triple negative breast cancer, the lentinan can down-regulate the protein of SCGB2A2 and / or mRNA expression level to inhibit the growth of triple negative breast cancer cells (such as MDA-MB-468, MDA-MB-436 and / or MDA-MB-231 cells). The lentinan is found to be capable of effectively treating the triple negative breast cancer, and the lentinan regulates SCGB2A2, so that the problem of lack of triple negative breast cancer treatment targets in the prior art is solved at the same time.

The invention relates to lentinan as well as a preparation method and application thereof, monosaccharide of the lentinan comprises glucose, galactose, mannose, fucose and glucosamine, and the molar ratio of the glucose to the galactose to the mannose to the fucose to the glucosamine is (85.0 to 88.0) to (5.5 to 6.5) to (3.5 to 4.1) to (1.8 to 2.2) to (1.0 to 1.2). According to the preparation method disclosed by the invention, a composite filler consisting of AB-8 macroporous resin and acidic aluminum oxide is adopted, static adsorption decoloration is carried out when the optimal mass ratio is 2: 3, an extraction process of combining graded hot water extraction with negative pressure concentration is optimized, and on the premise of avoiding using an organic solvent, efficient purification of lentinan is realized, so that the retention rate of the lentinan reaches 22.38%, and the yield of the lentinan is improved. And the beta-triple helix active structure can be well reserved.

The application discloses a bacillus zoogleoides BZ-32 and application of metabolites of the bacillus zoogleoides BZ-32 in vegetable stress resistance, and an effective component of the application is composed of bacillus zoogleoides fermentation liquor or metabolites, choline chloride and lentinan, wherein the weight percentage of the bacillus zoogleoides, choline chloride and lentinan is respectively 5-30% of bacillus zoogleoides metabolites, 5-30% of choline chloride and 0.2-5.0% of lentinan. The plant stress resistance composition can prevent and treat diseases such as root rot, anthracnose and powdery mildew of vegetables, and can prevent stress caused by excessively low temperature in winter and spring frost, and improve disease resistance and stress resistance of crops. The application can also be used for preventing and treating various corn diseases and strawberry diseases, and promoting growth and improving stress resistance.

An alcohol-free method of extracting β-glucans such as lentinan from mushrooms is described. The method excludes the drying and pulverising of the mushrooms prior to extraction. The simultaneous use of enzymatic digestion and ultrasonication provides extracts with high levels of desired properties including 1,1-diphenyl-2-picryl hydrazyl radial scavenging activity, superoxide radical scavenging activity, iron chelating capacity, and ferric-reducing antioxidant power.

The invention provides a nano-selenium preparation for targeted regulation of GPx3 expression, a preparation method of the nano-selenium preparation and application of the nano-selenium preparation in anti-tumor drugs, especially application of the nano-selenium preparation in anti-prostatic cancer drugs. The preparation method comprises the following steps: respectively mixing a sodium selenite solution with an LET (lentinan) solution, water and a VC (vitamin C) solution for reaction, then separating and purifying the reaction solution, and filtering to obtain the nano-selenium preparation for targeted regulation of GPx3 expression. The invention aims to provide a novel nano-selenium preparation which has higher anti-tumor activity and lower toxicity on prostatic cancer.

The invention relates to the technical field of seed treatment, and particularly discloses a seed treatment suspending agent containing prothioconazole, fludioxonil and chlorantraniliprole and a preparation method of the seed treatment suspending agent. The invention discloses a seed treatment suspending agent containing prothioconazole, fludioxonil and chlorantraniliprole. The suspending agent is prepared from the following raw material components in percentage by mass: 5 to 10 percent of prothioconazole microcapsules, 1 to 5 percent of silicon carrier loaded fludioxonil, 1 to 3 percent of chlorantraniliprole, 0.3 to 0.7 percent of lentinan, 0.3 to 0.7 percent of humic acid, 0.3 to 0.7 percent of chelated zinc, 10 to 15 percent of ethylene glycol, 3 to 5 percent of filler, 0.5 to 1.5 percent of dispersing agent, 0.05 to 0.15 percent of thickening agent, 2 to 3 percent of film-forming agent, 10 to 15 percent of oil and the balance of deionized water. The suspending agent disclosed by the invention not only has a relatively good prevention and treatment effect on wheat root rot, but also has a relatively high germination rate of treated wheat seeds.

The invention relates to the technical field of biological medicines, in particular to an injection for treating AIDS and a preparation method thereof. The extraction method of the sulfate algae polysaccharide comprises the following steps: mixing seaweed meal, cellulase and water, carrying out enzymolysis, and extracting for 10-12 hours to obtain an extract; filtering, adding magnesium chloride hexahydrate into filtrate, standing for 20-30 minutes, centrifuging, taking supernatant, removing impurities, adding absolute ethyl alcohol until the final concentration is 55-65%, and precipitating polysaccharide; and purifying the precipitated crude polysaccharide, and freeze-drying to obtain the sulfate algae polysaccharide. The purity of the sulfate algae polysaccharide is greater than or equal to 95%, and the sulfate algae polysaccharide is cooperated with lentinan to obtain a safe and stable injection with an excellent treatment effect on AIDS (Acquired Immune Deficiency Syndrome). And a new scheme is provided for treatment of AIDS.

The invention discloses a fertilizer for improving waterlogging tolerance of plants and application of the fertilizer, and belongs to the technical field of agricultural fertilizers. Comprising the following components in parts by weight: 20-40 parts of ground phosphate rock, 20-30 parts of oyster shell powder, 20-30 parts of urea, 15-20 parts of potassium chloride, 10-20 parts of illite powder and 8-12 parts of lentinan. The phosphorite powder, the oyster shell powder, the potassium chloride, the illite powder and the lentinan are compounded for the first time, and a'mineral nutrition regulation-soil physical improvement-plant immune activation 'three-in-one synergistic anti-waterlogging technical system is constructed. All the components complement each other and have synergistic interaction, and the anti-waterlogging effect is far better than that of a single component or conventional fertilizer. The functional anti-waterlogging fertilizer fills the technical blank of functional anti-waterlogging fertilizers, provides an innovative solution for stress resistance and stable yield of crops with the comprehensive advantages of low cost, high efficiency and environmental protection, and has remarkable economic benefits and social benefits.

The present invention belongs to the technical field of pesticides and provides a regulator for highland barley and preparation method and application thereof. The regulator uses water as a solvent and includes components with the following concentrations: 60-84 g / L of lentinan, 150-210 g / L of ethephon, 100-140 g / L of polyaspartic acid salt, and 15-25 mL / L of active agent. The regulator of the present invention can induce highland barley to establish a huge root system, increase the toughness of highland barley stems, dwarf the length of highland barley internodes, reduce plant height, and improve the ability of highland barley to resist lodging; at the same time, it can improve the photosynthetic performance of highland barley leaves and the development of spikes, and promotes high and stable yield of highland barley.

The invention discloses a botanical antiviral agricultural composition and application thereof, and belongs to the field of pesticides. The invention provides a botanical antiviral agricultural composition, the effective components of which are formed by binary compounding of sterol and lentinan, and the mass ratio of the sterol to the lentinan is (1: 5)-(1: 160). The composition provided by the invention shows a synergistic interaction effect on the tomato yellow leaf curl virus (TYLCV) in a specific ratio range.

The present application relates to the field of synthetic biology, and specifically discloses a preparation method for improving the biological activity of lentinan and application thereof. The method adopts white shiitake mushroom to perform solid-state fermentation on lentinan, and comprises the following steps: S1, grinding the lentinan into powder, then adding appropriate amount of water to stir uniformly, high-pressure sterilization, and cooling to obtain lentinan culture medium; S2, activating white shiitake mushroom strains and preparing white shiitake mushroom seed liquid, adding the white shiitake mushroom seed liquid into the lentinan culture medium according to a certain inoculation amount to perform solid-state fermentation; S3, taking the fermented lentinan culture medium, performing protease enzymolysis first, then adopting ethanol precipitation, centrifuging to take the precipitate, resolubilizing the precipitate, performing dialysis treatment through a dialysis bag, and freeze-drying the dialyzed solution to obtain lentinan. The preparation method significantly improves the yield and purity of lentinan, and at the same time, the antioxidant, anti-inflammatory and pancreatic lipase clearance abilities are significantly improved, and the method has the effect of lubricating intestines.

This invention discloses a brewed vinegar rich in lentinan and its preparation method. Using the lentinan variety "Shenxiang 1513" as raw material, the invention obtains a lentinan extract through water extraction and concentration, wherein the lentinan content is ≥0.5%. The obtained lentinan extract is then compounded with solid-state fermented vinegar at a mass ratio of 1:50-100, aged at 20-30℃ for 15-30 days, and then filtered and sterilized to obtain the finished product. The lentinan vinegar prepared by this invention does not contain any preservatives, umami agents, or sweeteners. The final product contains lentinan ≥50 mg / 100 mL, total acid ≥5.00 g / 100 mL, exhibits a harmonious flavor, stable quality, and clearly defined functional components and excellent flavoring properties.

The invention discloses a functional food for improving immunity and belongs to the field of health-care foods. Comprising the following substances in parts by weight: 15-20 parts of chitosan oligosaccharide, 4-6 parts of astragalus polysaccharide, 2-4 parts of lucid ganoderma oligosaccharide, 2-4 parts of Chinese wolfberry oligosaccharide, 1-2 parts of codonopsis pilosula polysaccharide, 2-4 parts of ginseng oligosaccharide, 6-8 parts of lentinan, 6-10 parts of Chinese yam polysaccharide, 2-4 parts of oat peptide, 1-2 parts of pericarpium citri reticulatae polysaccharide, 6-8 parts of soybean peptide and 10-15 parts of whey protein peptide. The various components have a synergistic effect, the polysaccharide components can enhance the activity of immune cells, the peptide substances can promote the generation of immune factors, and the synergistic effect of the polysaccharide components and the peptide substances is beneficial for improving the immune defense capability of the body and improving the immunity of the human body.

This invention belongs to the field of pharmaceutical formulation, drug delivery, and vaccine technology, and relates to a method for preparing alkylated lentinan and its application in lipid nanoparticle (LNP) vaccines. This invention modifies lentinan by alkylation, enabling it to dissolve efficiently in lipid nanoparticles (LNPs), making it suitable for the preparation of LNP mRNA vaccines. Using the alkylated lentinan of this invention to prepare mRNA vaccines allows for the co-loading / assembly of alkylated lentinan and mRNA into the same lipid nanoparticle delivery system, creating an integrated antigen and adjuvant vaccine system. This solves the problems in existing technologies, significantly enhances the strength and breadth of anti-tumor immune responses, and features high safety, efficient immune activation, and strong targeting, making it widely applicable for tumor prevention and treatment.

The invention provides lentinan as well as a preparation method and application thereof, and belongs to the technical field of plant protection. According to the preparation method, a ZTC 1 + 1 II type clarifying agent is used, and step-by-step flocculation purification is carried out at 50 DEG C according to a sequence of firstly adding a component B and then adding a component A and specific stirring parameters. According to the process, impurities such as protein are efficiently removed, the active conformation of lentinan is well reserved, and the antiviral activity of the product is remarkably improved. Meanwhile, the invention finds that when the lentinan obtained by the invention is mixed with oligosaccharin.chain protein in a mass ratio of 7: 3 or 9: 1, the lentinan shows a remarkable specific synergistic effect. The invention solves the problems of poor product stability and large activity loss in the prior art, and is especially suitable for prevention and treatment of plant virus diseases such as tomato mosaic virus diseases.