298 results about "Biological macromolecule" patented technology

The application discloses a chromatography material raw material composition, a chromatography material and a preparation method and application thereof, a whole column and a chromatography pile. The chromatography material raw material composition, with the total weight of raw material A and pore former B being 100%, comprises the following components: 20%-70% of raw material A; 30%-80% of pore former B; 0.1 ‰-1 ‰ of catalyst C; and the raw material A comprises a substance containing a polycyclic epoxy group. The chromatography material composition of the application can solve the pain points of the application of the current chromatography microsphere filler on biological macromolecules. The chromatography material has the advantages of uniform internal structure, good preparation reproducibility, high toughness, modifiable functional ligand and high hydrophilicity, and is more suitable for the separation and purification of biological molecules.

The invention provides a preparation method of a calcium emulsifying and embedding system with high bioaccessibility, which comprises the following steps: S1) heating and mixing biomacromolecules and an emulsifier in water to obtain a water phase; the biomacromolecules are protein colloids and / or polysaccharide colloids; the method comprises the following steps: heating and mixing a calcium source substance and anhydrous cream to obtain an oil-solid phase; and S2) mixing the oil-solid phase with a water phase, and emulsifying to obtain the calcium emulsifying and embedding system. Compared with the prior art, the preparation method has the advantages that the natural macromolecular protein and / or polysaccharide with high nutritional value is used as a carrier, the calcium source substance is embedded through a water-oil-solid three-phase emulsification technology, and the preparation method is simple, easy to operate, low in cost and environmentally friendly; in addition, a water-oil-solid three-phase homogenized emulsion is created, the problem that the dispersion stability of milk mineral salt in a liquid food matrix is poor is effectively solved, release of free calcium ions in the small intestine environment can be promoted, and the calcium bioaccessibility is remarkably improved.

The invention relates to an anti-inflammatory and repair-promoting hydrogel for a uterine cavity as well as a preparation method and application of the anti-inflammatory and repair-promoting hydrogel, and relates to the technical field of biological medicines. The uterine cavity anti-inflammatory and repair-promoting hydrogel is prepared from the following raw materials: an anti-inflammatory component, a biomacromolecule with active ester and an amino high-molecular polymer. The hydrogel for resisting inflammation and promoting repair of the uterine cavity, which is prepared by the invention, has good biological safety, injectability and adhesiveness with tissues; in intrauterine adhesion prevention treatment, a three-dimensional network structure formed by crosslinking of the biomacromolecules with the active ester and the amino high-molecular polymer plays a physical isolation role, the anti-inflammatory component plays an anti-inflammatory role by inhibiting expression of an inflammation signal channel, and the biomacromolecules with the active ester and the amino high-molecular polymer achieve a synergistic treatment effect.

The invention belongs to the technical field of membrane separation, and particularly relates to a low-pressure high-flux polyamide / polysulfone hollow fiber composite nanofiltration membrane and a preparation method thereof. The preparation method of the composite nanofiltration membrane comprises the following steps: dissolving sulfonated polysulfone, poly (1-vinyl-3-butylimidazole) bromide and polyvinylpyrrolidone to prepare a spinning solution, and spinning to obtain a base membrane; carrying out hydrophilic modification on the base membrane by using 1, 3-propane sultone; then, an aqueous phase solution containing poly (gamma-glutamic acid) and triethylene tetramine and an organic phase solution containing trimesoyl chloride and 3, 5-diaminobenzoic acid are subjected to interfacial polymerization in the inner cavity of the modified base membrane to form a polyamide separation layer; and finally, carrying out heat treatment to obtain the composite nanofiltration membrane. Through the synergistic effect of zwitterionic ionization of the base membrane and biomacromolecule construction of the separation layer, the mass transfer resistance of water is remarkably reduced, unification of high flux and high selectivity is achieved, and good structural stability is achieved.

The invention relates to the technical field of ion characterization and preparation, in particular to a high-throughput preparation mass spectrum device and method giving consideration to high-resolution characterization. The device comprises an ion source, an ion transmission cavity, a quadrupole mass screening cavity, an ion dissociation cavity, an ion deflection cavity, an ion deceleration and deposition cavity and a high-resolution mass spectrum characterization cavity which are sequentially arranged, wherein the high-resolution mass spectrum characterization cavity is formed in one side of the ion deflection cavity in the vertical direction; soft ionization is combined with a quadrupole analyzer to screen ions, the ions are dissociated through a dissociation cavity, an ion deflection cavity is used for selecting a high-resolution characterization or high-throughput preparation function, a high-resolution mass spectrum characterization cavity is used for achieving high-resolution characterization of screened and fragmented ions, and an ion deceleration and deposition cavity is used for high-throughput preparation of the ions. According to the method, perfect compatibility of high-throughput preparation and high-resolution mass spectrum characterization is realized through ion deflection design, and the method has a wide application prospect in the fields of efficient preparation of biological macromolecules, synthetic macromolecules and the like and the like.

The invention discloses a method for realizing high-efficiency selenium labeling of protein, which comprises the following steps of: in the process of expressing plasmids containing target protein through a prokaryote expression system, realizing high-efficiency replacement of cysteine sulfur atoms in the target protein by selenium atoms by regulating and controlling the ratio of selenium to sulfur elements in a culture medium; on the premise of keeping a good growth state of cells, the selenium labeling efficiency can reach 86%, and the protein expression quantity is stabilized at about 1mg / g (protein / thallus wet weight); structural analysis shows that the secondary structure of the obtained selenium-labeled protein is basically consistent with that of natural protein and is not obviously changed. The method is easy and convenient to operate, high in labeling efficiency, high in protein yield, good in repeatability and suitable for structural biology research such as nuclear magnetic resonance, an effective means is provided for research of the functional mechanism of sulfur atoms in biomacromolecules (including small peptides, polypeptides, peptide fragments, proteins and protein or peptide complexes) with selenium as a probe, and the method has a wide application prospect. Good scientific research application prospects and industrial popularization values are realized.

The invention belongs to the technical field of nano-drugs, and particularly relates to an artificially evolved protein cage nano-drug as well as a preparation method and application thereof. The artificial evolution protein cage nano-drug provided by the invention comprises an artificial evolution protein cage and a nucleic acid biomacromolecular drug, the artificial evolution protein cage is obtained by artificially obtaining a 240 polymer nano-protein cage C27-A with a PDB number of 6NJ8 by an artificial evolution system, and the amino acid sequence of a protein subunit of the artificial evolution protein cage is as shown in SEQ ID NO.1; the artificially evolved protein cage can be used for efficiently packaging nucleic acid type biological macromolecular drugs inside, has the advantages of high protein yield, good stability, good tumor treatment effect, excellent safety and the like, and can solve the technical problem of low drug packaging efficiency of protein cage nano drugs in the prior art.

The invention discloses immunoregulation hydrogel based on ginsenoside Rd, a preparation method and application, and relates to the technical field of biomedical materials and hydrogels. The hydrogel is prepared by taking natural polysaccharides modified by phenylboronic acid groups, derivatives of the natural polysaccharides and methacrylic anhydride modified protein biopolymers as biological matrix materials; ginsenoside Rd is used as a bioactive functional component, and polyvinyl alcohol is used as a cross-linking agent; a first dynamic reversible cross-linked network is formed through chemical cross-linking, and is endowed with injectability, self-healing property and glucose responsiveness; ginsenoside Rd is taken as a main raw material and then subjected to addition polymerization reaction under the irradiation of a photoinitiator and light, a second static covalent cross-linked network is formed, mechanical strength and structural stability are given to the system, in addition, ginsenoside Rd is loaded in the system through boric acid ester bonds, and the slow-release effect is achieved. The problems of stability and bioavailability during local application of the Chinese herbal medicine extract are solved, and healing of chronic and serious wounds can be more effectively promoted.

The invention relates to the technical field of biomacromolecule separation and purification engineering, and discloses a chromatographic separation method for removing endotoxin in a vaccine preparation, which comprises the following steps: preparing an equilibrium buffer solution containing citrate with specific concentration and L-arginine hydrochloride; providing a mixed mode chromatography medium with hydrophobic and ion exchange complex ligands and balancing with a buffer; according to the method, through the synergistic effect of 8.0-12.0 mmol / L of citrate and 150-250 mmol / L of L-arginine hydrochloride, the endotoxin micelle structure is destroyed and is induced to be dissociated into monomers, and meanwhile, L-arginine is used for inhibiting monomer aggregation, so that the monomers are diffused into inner holes of the medium in a small size to be adsorbed, and the endotoxin micelle structure is separated into the medium. Therefore, the problem of separation caused by size overlapping of endotoxin micelles and antigens is solved, and double breakthrough of deep removal of endotoxin and high recovery rate of antigens is realized.

The invention relates to the technical field of building materials, in particular to a bio-based multifunctional sound insulation wallboard and a preparation method thereof. The wallboard comprises a sound absorption layer and a sound insulation layer. The sound absorption layer is cooperatively constructed by an inactivated mycelium three-dimensional porous framework and microalgae biomass, and the sound insulation layer is a high-density complex formed by compounding bio-based raw materials such as wood fiber, straw, recycled paper pulp and shell filler. And the two are combined through a biological-physical mechanical interlocking interface formed by hypha growth, extension and embedding to form a natural acoustic gradient structure from porous low acoustic impedance to compact high acoustic impedance. According to the preparation method, an in-situ growth process of mycelium culture and microalgae coating is embedded into a hot-pressing process, a three-dimensional anchoring network is formed by actively embedding mycelia into the sound insulation layer, the microalgae permeates into pores and is subjected to hot pressing to generate biomacromolecules for bonding and filling, a porous structure is synchronously constructed by a one-step method, and firm interlayer bonding is realized. The wallboard has excellent broadband acoustic performance, stable bonding strength and low-carbon and environment-friendly benefits.

The invention relates to an aptamer specifically combined with beta-lactoglobulin and application of the aptamer, and belongs to the technical field of biological detection. According to the aptamer and the preparation method thereof, a binding domain base, participating in recognition, of the aptamer is predicted through molecular docking firstly, then the binding domain base is subjected to directional mutation, the aptamer with the recognition performance improved is obtained, the affinity of the aptamer to beta-lactoglobulin is 10.6 nM, and the aptamer has no recognition capacity on alpha-lactalbumin, casein, bovine serum albumin, immune globulin G, lactose and the like and can be used for preparing the aptamer with the recognition performance improved. Therefore, the aptamer disclosed by the invention has good sensitivity and specificity on the beta-lactoglobulin. On the basis, a fluorescence polarization method is directly constructed by utilizing the characteristic that the beta-lactoglobulin is a biomacromolecule, when the beta-lactoglobulin exists, an aptamer marked by a fluorophore FAM recognizes the beta-lactoglobulin to form an aptamer beta-lactoglobulin compound, and the fluorescence polarization value is relatively large, so that the beta-lactoglobulin compound can be used for identifying the beta-lactoglobulin. Therefore, the specific detection of the low-concentration beta-lactoglobulin is realized.

Disclosed in the present invention is a monolithic column material. Quaternary ammonium groups are grafted onto the inner surfaces of pores and channels of the monolithic column material. The quaternary ammonium group is present in the form of EP-OCH2CH(OH)CH-N+R1R2R3. The monolithic column prepared in the present invention is rich in hydroxyl, has excellent compatibility with an eluted analyte containing biomacromolecules, has excellent specific adsorption capacity for nucleic acid substances, and is suitable for enrichment and separation of DNA and / or RNA substances.

The present invention relates to an isolated peptide comprising the amino acid sequence of Formula (I): (O)n-K-(O)m-Z; wherein K is lysine optionally modified with a self-immolative moiety Z is tryptophan or is absent; O is GHGX1Y (SEQ ID NO: 1); G is glycine, H is histidine, Y is tyrosine; each X1 is independently selected from alanine, glycine, serine, asparagine, histidine (H), arginine (R), aspartic acid, tyrosine, and proline; n is 0 – 5; m is 0 – 5; n+m is 3, 4, 5, 6, 7 or 8, and optionally, wherein not all of the X1 residues are proline (P). Such peptide is a coacervate forming peptide. The present invention also relates to methods of preparing coacervate compositions comprising the isolated peptide, optionally also comprising one or more biomacromolecules (payloads). The present invention further relates to the coacervate compositions per se, and their uses, e.g. in methods of treatment or diagnosis.

The invention discloses a compound for preventing and treating related diseases caused by aldehyde metabolism disorder and application of the compound. The compound is a compound as shown in a formula (I) or a stereoisomer, a tautomer, a solvate and pharmaceutically acceptable salt of the compound as shown in the formula (I). The compound can be combined with active aldehyde to reduce the generation of an active aldehyde-biomacromolecule adduct and play a role in removing aldehyde, and can be used for treating various system diseases caused by aldehyde metabolism disorder. # imgabs0 #

The invention provides a biosensor based on heterostructure double holes and a preparation method and application thereof. The device comprises a silicon nitride chip fixed between two electrolyte-filled liquid storage tanks, a layer of graphene film is transferred on the silicon nitride chip in advance, one nanopore is etched on a graphene interface, and the other nanopore is etched on a silicon nitride interface. The two side liquid pools are respectively connected with the positive electrode and the negative electrode of the patch clamp amplifier. When a certain potential difference is applied to the two electrodes, the biological macromolecules in the liquid pool can be captured into the nanometer channel. When two ends of a molecule are captured by two different nanopores at the same time, due to different interaction between a silicon nitride-graphene heterogeneous interface and the molecule and the action of electric field force, the molecule can form a dragsaw phenomenon between the two pores, and the time of the molecule passing through the nanopores is prolonged. According to the invention, the rate of chain molecules such as DNA, protein and the like passing through the nanopore can be regulated and controlled, and accurate control of single molecules and even gene sequencing can be realized.

The invention relates to a circulating tumor cell enrichment, separation and dyeing integrated system and application thereof.The circulating tumor cell enrichment, separation and dyeing integrated system is composed of a bottom plate module, a platform module, a multi-pipette module, a power module and a shell module; the platform module comprises a sample tube rotating and uniformly mixing module, a magnetic adsorption module, a reagent module, a waste liquid pool module and a gun head module, and the sample tube rotating and uniformly mixing module, the magnetic adsorption module and the reagent module are fixedly mounted on a bottom plate I in sequence. The CTC separation and dyeing integrated system is developed on the basis of the immunomagnetic bead technology, enrichment separation and immunofluorescent dyeing of CTC can be automatically completed by running a program, manual operation errors are effectively avoided through a programmed process, and the CTC separation and dyeing integrated system is particularly suitable for clinical CTC detection. The system is also suitable for other enrichment and separation applications based on an immunomagnetic bead technology, including but not limited to enrichment and separation of biological macromolecules such as cells, exosomes, proteins and the like.

Provided is an antibody-drug conjugate. Specifically, the conjugate couples a cytotoxic substance and a biological macromolecule by means of a novel linker. The prepared antibody-drug conjugate has an excellent activity of inhibiting the growth of tumor cells.

The invention discloses a preparation method and application of a myofibrillar protein emulsion based on enzymatic modification. According to the technology, a myofibrillar protein aqueous suspension is subjected to enzymatic deamidation and glycosylation reaction through protein glutaminase and glucan, a protein-polysaccharide compound with good emulsifying performance is constructed, soybean oil serves as an oil phase, and emulsion systems with different oil phase volume fractions are constructed through a controllable homogenizing technology. The obtained emulsion has the characteristics of natural degradability, excellent rheological property, uniform particle size distribution, long-term physical stability and the like. Compared with a traditional chemical modification technology, the technology adopts a whole bio-based raw material combined enzyme method green technology, the problems of organic solvent residues and the like are effectively solved, and the production cost is reduced while the product safety is ensured. The emulsion has remarkable application advantages in the fields of functional food active ingredient delivery, drug controlled release carriers, cosmetic transdermal absorption systems and the like, and a new thought is provided for development of a biomacromolecule-based delivery system.

Disclosed is a monolithic column material, primary amine groups or secondary amine groups or tertiary amine groups being grafted on the internal surfaces of pores and channels of the monolithic column material. The primary amine groups, secondary amine groups or tertiary amine groups exist in the form of EP-OCH2CH(OH)CH-NR1R2. A monolithic column prepared by the present invention is rich in hydroxyl groups, has excellent compatibility with elution objects containing biological macromolecules, and also has excellent specific adsorption capacity for nucleic acid substances, making it suitable for enrichment and separation of DNA and / or RNA substances.

The application discloses application of mangiferin as a broad-spectrum inhibitor of active carbonyl compounds, and provides application of mangiferin (MGF) as an acrolein (ACR), methyl glyoxal (MGO) and glyoxal (GO) inhibitor, wherein, compared with the prior art, the application discloses a new application of mangiferin or a one-addition product of the mangiferin and the active carbonyl compound, that is, the mangiferin or the one-addition product can effectively capture ACR, MGO and GO to control the content of the ACR, MGO and GO and avoid the ACR, MGO and GO from reacting with nucleophilic biological macromolecules to form various harmful addition or cross-linking products. The mangiferin or the one-addition product of the mangiferin and the active carbonyl compound can be used as a scavenger of ACR, MGO and GO, so that the ACR, MGO and GO generated in the body and in a food processing process are inhibited, and thus the various harmful addition or cross-linking products formed by the reaction of RCS with the nucleophilic biological macromolecules are blocked to cause harm to the human body.

The present invention relates to nanoparticles complexed with biomacromolecule agents configured for treating, preventing or ameliorating various types of disorders, and methods of synthesizing the same. In particular, the present invention is directed to compositions comprising nanoparticles (e.g., synthetic high density lipoprotein (sHDL)) carrying biomacromolecule agents (e.g., nucleic acid, peptides, glycolipids, etc.), methods for synthesizing such nanoparticles, as well as systems and methods utilizing such nanoparticles (e.g., in diagnostic and / or therapeutic settings).

The present invention discloses the use of a DNA nanostructure as an antifreeze agent. DNA, a biomacromolecule essential for the development and normal functioning of organisms, possesses excellent programmability and biocompatibility. This invention provides a general approach to the antifreeze field, using specific types of DNA nanostructures as antifreeze agents. The hydrophobic bases of DNA tend to adsorb onto tiny ice crystals, stabilizing the entire material system with the help of hydrophilic ribose phosphate chains. This Kelvin effect achieves excellent ice suppression, effectively inhibiting ice recrystallization at relatively low concentrations. The DNA nanostructures used as antifreeze agents in the present invention have simple and rapid preparation processes, good biocompatibility, and structural predictability. Different material sizes and morphologies can be designed to achieve varying antifreeze effects.

The invention relates to an oxime ester type carbon dot photoinitiator, the surface of a carbon dot is provided with a group containing an oxime ester structure part, and the average particle size of the carbon dot is 1-50nm. The oxime ester type carbon dot photoinitiator as a photoinitiator can show good initiation performance in a range of 200-1200 nm, especially 250-660 nm, and can effectively initiate a photopolymerization reaction of a photopolymerizable monomer, especially a (methyl) acrylate monomer. The invention also relates to a preparation method and application of the oxime ester type carbon dot photoinitiator. The oxime ester type carbon dot photoinitiator is especially suitable for UV-VIS LED light source curing. The photoinitiator disclosed by the invention is low in biotoxicity, low in migration rate and excellent in biocompatibility, can be applied to the fields of photopolymerization materials, biomacromolecules and the like, and is simple in synthesis route, so that the photoinitiator has extremely high practical value.

The application discloses a biological macromolecule sequence structure prediction method, and relates to the technical field of computers. In the diffusion process, a geometric position coding gating mechanism is introduced, and a multi-scale attention broadcast mechanism is used to broadcast the attention weights corresponding to different attention types of the target information processed in different broadcast range modes, and the attention weights in different time steps in the broadcast range are reused, so that the same attention weight is used in the steps of the broadcast range, the calculation amount is reduced, the model efficiency performance is improved, the perception ability of the model to the amino acid position information in the protein sequence can be effectively improved, the model can fully consider the position relationship between amino acids when calculating the attention weight, the model can better identify the long-chain amino acid interaction, the structure prediction error caused by the missing position information is reduced, and the prediction precision is improved.

The invention provides a mannan oligosaccharide fertilizer synergist with a biological synergistic function and a high-utilization-rate fertilizer. The mannan oligosaccharide fertilizer synergist comprises phosphorylated modified mannan oligosaccharide, mannan oligosaccharide, mannan oligosaccharide, mannan oligosaccharide, mannan oligosaccharide, mannan oligosaccharide, mannan oligosaccharide, mannan oligosaccharide and mannan oligosaccharide, the phosphorylated modified mannan oligosaccharide is obtained by carrying out phosphorylation reaction on mannan oligosaccharide through a phosphorylation reagent. According to the mannan oligosaccharide fertilizer synergist with the biological synergistic function and the high-utilization-rate fertilizer, mannan oligosaccharide is subjected to phosphorylation reaction to obtain phosphorylated modified mannan oligosaccharide which serves as the fertilizer synergist, compared with mannan oligosaccharide or other saccharides, the affinity of the phosphorylated modified mannan oligosaccharide with biomacromolecules such as films, enzymes and proteins is greatly improved, and the utilization rate of the fertilizer synergist is increased; while biological synergism is realized, absorption of nitrogen, phosphorus and potassium can be promoted, and the utilization rate of the fertilizer is increased.

The invention discloses a zinc ion battery electrolyte containing phycocyanin as well as a preparation method and application of the zinc ion battery electrolyte. The zinc ion battery electrolyte is prepared from soluble zinc salt, phycocyanin and water, wherein the concentration of the phycocyanin is 0.1 mmol / L to 0.5 mmol / L; the concentration of the soluble zinc salt is 1 mol / L to 2 mol / L. In the zinc ion battery electrolyte disclosed by the invention, phycocyanin is a natural biomacromolecule which is natural, non-toxic, low in cost and environment-friendly, has various structures and is rich in various active functional groups, and the problems of high toxicity, single function, poor economic benefit and high cost of an organic additive in the prior art are solved. Besides, the zinc ion battery electrolyte can inhibit dendritic crystal growth, a stable interface layer is formed on the surface of a zinc negative electrode, side reactions are reduced, and the cycling stability and coulombic efficiency of the battery are improved.

The invention discloses a method for preparing a biomacromolecular drug delivery carrier based on a simple and efficient interface cross-linking system. An amphiphilic polymer monomer containing an epoxy group is prepared through RAFT polymerization so that the amphiphilic polymer monomer can exist on an oil-water interface, meanwhile, a three-arm cross-linking agent which has environmental sensitivity and is terminated by an amino group is prepared, and the amino group on the cross-linking agent and the epoxy group on the amphiphilic monomer are subjected to a cross-linking reaction on the oil-water interface; a drug delivery vehicle is formed. The carrier can entrap biomacromolecules and accurately target tumors through a high-permeability long-retention effect, and glutathione rich in a tumor microenvironment can break disulfide bonds in the carrier and release drugs entrapped in the carrier, so that the aim of treating the tumors is fulfilled. Therefore, the invention provides a drug delivery carrier which is simple, convenient, efficient in entrapment of biomacromolecules and high in stability, and the prepared carrier can be efficiently taken by tumor cells so as to regulate and control apoptosis of the tumor cells and is high in safety.

The present invention relates to an oxime-ester-type carbon dot photoinitiator, wherein the surface of a carbon dot has a group containing an oxime ester structure moiety, and the carbon dot has an average particle size of 1-50 nm. As a photoinitiator, the oxime-ester-type carbon dot photoinitiator can exhibit good initiation performance within a range of 200-1,200 nm, especially 250-660 nm, and can effectively initiate a photopolymerization reaction of a photopolymerizable monomer, especially a (meth)acrylate monomer. The present invention further relates to a method for preparing the oxime-ester-type carbon dot photoinitiator and a use of the oxime-ester-type carbon dot photoinitiator. The oxime-ester-type carbon dot photoinitiator is especially suitable for curing under a UV-VIS LED light source. The photoinitiator of the present invention has low biotoxicity and low mobility, also has excellent biocompatibility, can be used in the fields such as photopolymerizable materials and biomacromolecules, and has a simple synthesis route, thereby achieving an extremely high practical value.

The present invention belongs to the field of food processing, and provides a non-thermally processed hot pot base and a preparation method thereof; white wine is added to the pretreated raw materials for static extraction, and composite phosphates are added to maintain the stability of the flavor of the material during subsequent processing and storage. After a first high-voltage pulse electric field treatment, the cell membrane of the raw materials is destroyed, allowing the biological macromolecules in the raw materials to fully overflow, inactivating the activity of enzymes to protect the color of the material. After a second high-voltage pulse electric field treatment, the formation of characteristic flavor components of the material is promoted, and microorganisms introduced during the processing are killed. Compared with the prior art, the hot pot base has a bright color and a rich characteristic flavor, and the base has improved boiling resistance and flavor release, thereby improving the overall quality of the product. The preparation method of the present invention is applied to the processing of spicy clear oil hot pot base, and a hot pot base with controllable spiciness and prominent numbness can be obtained.