533 results about "Antimicrobial peptides" patented technology

The invention discloses an antibacterial peptide and application thereof, and belongs to the technical field of biology. The antibacterial peptide with an inhibition effect on various clinically common pathogenic microorganisms is obtained, and the antibacterial peptide comprises gram-negative bacteria such as escherichia coli, klebsiella pneumoniae, pseudomonas aeruginosa, acinetobacter baumannii, vibrio parahaemolyticus, salmonella gallinarum, salmonella typhimurium and enterobacter sakazakii, and gram-positive bacteria. The antibacterial peptide provided by the invention can be used as an antibacterial peptide, such as staphylococcus aureus, listeria monocytogenes and bacillus cereus, and the antibacterial peptide provided by the invention is novel in structure and easy to prepare.

The invention relates to the technical field of computer-aided drug research and development, and provides an antibacterial peptide function recognition optimization method and system based on deep learning and LLM. Systematic innovation is performed in multiple links such as feature extraction, data generation and reasoning verification by introducing a fusion mechanism of a large language model and a deep learning model; and the accuracy and robustness of antibacterial peptide function prediction are obviously improved. On one hand, a strict feature extraction process and a structured cue word template are constructed, sequence information and physicochemical property indexes of the antibacterial peptide and a prediction result of a deep learning model can be effectively integrated, and the prediction result is reasonably corrected and optimized through the reasoning ability and knowledge verification mechanism of a large language model. The misjudgment risk of a traditional deep learning method under the condition of insufficient samples or incomplete features is effectively reduced, and the prediction accuracy and stability are remarkably improved.

Provided is an antibacterial peptide having an amino acid sequence X1KRFKKFFX2KLKKWV-NH2, wherein X1 is selected from any one or of amino acids A, C, D, E, F, G, H, K, L, N, M, P, Q, R, S, I, V, W, Y, and T or is absent; and X2 is an amino acid having an aromatic side chain or an amino acid having an alkaline side chain. In view of defects such as poor gastrointestinal fluid stability of antibacterial peptides in the prior art, a brand-new sequence design scheme and preparation method for an antibacterial peptide are provided. By means of a complete or partial D-amino acid substitution or structural derivatization of a peptide sequence, a series of antimicrobial peptides having stronger antibacterial activity and gastrointestinal stability as compared with the prior art are obtained, such that the antibacterial peptides have a wider application range and higher development potential value.

A query-based generic end-to-end molecular optimization (“QMO”) system framework, method and computer program product for optimizing molecules, such as for accelerating drug discovery. The QMO framework decouples representation learning and guided search and applies to any plug-in encoder-decoder with continuous latent representations. QMO framework directly incorporates evaluations based on chemical modeling, analysis packages, and pre-trained machine-learned prediction models for efficient molecule optimization using a query-based guided search method based on zeroth order optimization. The QMO features efficient guided search with molecular property evaluations and constraints obtained using the predictive models and chemical modeling and analysis packages. QMO tasks include optimizing drug-likeness and penalized log P scores with similarity constraints and improving the target binding affinity of existing drugs to pathogens such as the SARS-CoV-2 main protease protein while preserving the desired drug properties. QMO tasks further improves optimizing antimicrobial peptides toward lower toxicity.

The invention discloses an antibacterial peptide simulant based on adamantane modification and application of the antibacterial peptide simulant. The preparation method comprises the following steps: performing amide condensation on Fmoc amino acid to obtain a compound of which the carboxyl terminal is modified by amantadine or Boc protected aliphatic amine, and then removing an Fmoc group by piperidine to obtain a series of amantadine modified crude products and Boc protected aliphatic amine modified intermediate compounds; the intermediate compound is subjected to amide condensation to obtain a compound of which the amino terminal is further modified by adamantanic acid, then other protecting groups are cracked by trifluoroacetic acid to obtain a series of adamantanic acid modified crude products, and the crude products are purified to obtain the adamantane modified peptidomimetic. The adamantane modified peptidomimetic is used for preparing drugs for treating infectious diseases caused by sensitive bacteria and drug-resistant bacteria, has efficient antibacterial activity and low toxicity, and is not influenced by a traditional drug-resistant mechanism.

The invention discloses a baicalin and boric acid antibacterial peptide assembly and a preparation method and application thereof, belongs to the technical field of biological medicine, and provides a baicalin and boric acid antibacterial peptide assembly which comprises baicalin and boric acid antibacterial peptide. The amino acid sequence of the boric acid antibacterial peptide is one of SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3, SEQ ID NO. 4, SEQ ID NO. 5 or SEQ ID NO. 6. According to the baicalin and boric acid antibacterial peptide assembly, phenylboronic acid molecules introduced to the C end of boric acid antibacterial peptide polypeptide can form boric acid ester bonds with the baicalin, the water solubility and membrane permeability of the baicalin can be improved, the baicalin can enter bacterial cells more easily to play a role, and the baicalin and the boric acid antibacterial peptide can form a multi-target synergistic antibacterial effect; therefore, the antibacterial effect is obviously improved.

The invention discloses a milk-flavor jelly-shaped intelligent response type suckling pig creep compound feed and a preparation method, relates to the technical field of animal feeds, and aims to solve the problems that a traditional feed is poor in palatability, nutrition release and physiological needs are mismatched, thermosensitive components are damaged by a high-temperature process and the like. And accurate release of nutrients is realized. The feed comprises an energy raw material, a protein raw material, intelligent response components (pH-sensitive sodium alginate microsphere loaded sodium butyrate / glutamine, temperature-sensitive xanthan gum-locust bean gum compound gel coated antibacterial peptide, and enzyme-sensitive lysine-lysine peptide bond cross-linked layer embedded glucose compound enzyme), a flavor system (vanillin microcapsules) and a konjac gum jelly matrix. A pH-temperature-enzyme triple response mechanism is adopted to adapt to the gastric acid gradient, body temperature fluctuation and pancreatin activity of suckling pigs; milk flavor slow release and nutrition release are in space-time synergy, and the ingestion frequency is increased by 40%; the konjac glucomannan matrix reduces dust, and the gel strength is greater than or equal to 750g / cm.

The invention discloses a functional probiotic composition and application thereof, and relates to the technical field of microbial engineering. Bifidobacterium longum, lactobacillus acidophilus and enterococcus faecalis are combined to serve as a microbial agent, the microbial agent and active substances of the tea leaves form a composition, then the composition is combined with prebiotics, it is ensured that viable bacteria directly reach the intestinal tract through a microencapsulation technology, and the effect of improving the immune function is achieved; tea polyphenol in the active substances of the tea leaves can serve as a carbon source of prebiotics to stimulate proliferation of the bifidobacterium longum and the lactobacillus acidophilus, so that the acid resistance and intestinal colonization capacity of the microbial inoculum are enhanced, and meanwhile, theanine in the active substances of the tea leaves, the bifidobacterium longum and the lactobacillus acidophilus synergistically promote secretion of gamma-aminobutyric acid, so that the effect of improving the intestinal colonization is achieved. And the tea polyphenol can inhibit the large intestine rod from adhering to the intestinal mucosa, and the probiotic agent secretes antibacterial peptide, so that the integrity of the intestinal barrier is maintained together.

The invention belongs to the technical field of gene engineering, and particularly relates to ALFPm3 modified antibacterial peptide, a molecular design and construction method and application of the ALFPm3 modified antibacterial peptide, and the amino acid sequence of the ALFPm3 modified antibacterial peptide is selected from any one of SEQ ID NO: 1-SEQ ID NO: 7. Analysis and design are carried out by combining the structure and action site of vibrio parahaemolyticus and the molecular structure and function relationship of the antibacterial peptide ALFPm3 as a basic template, the antibacterial activity of the antibacterial peptide ALFPm3 is improved, and other biological activities such as hemolysis are reduced.

The invention provides an antibacterial peptide derivative and application thereof. The antibacterial peptide derivative is any one of the following polypeptides (a)-(d): (a) polypeptides with an amino acid sequence as shown in a general formula (1) or a general formula (2): Ac-GX1aZOWX1bZOFWNOIOZ-NH2 (1) and Ac-GX2aPZOWX2bZOFWNOIOZ-NH2 (2), and the amino acid sequence of the polypeptides is shown in the general formula (1) or the general formula (2). The antibacterial peptide has excellent in-vitro antibacterial activity, relatively low hemolytic activity and relatively high anti-enzymolysis stability.

The present invention belongs to the field of biomedicine, and specifically relates to an antimicrobial peptide derived from lactoferrin and its application. The antimicrobial peptide derived from lactoferrin, whose amino acid sequence is shown in any one of SEQ ID NOs: 1 to 98, has a broad-spectrum antimicrobial effect, especially significant antibacterial effect against Pseudomonas putida, Rhodococcus erythropolis, Bacillus subtilis, Malassezia furfur, Cryptococcus neoformans, and Candida albicans, and has great application value.

The invention discloses an application of an antibacterial peptide and an application of the antibacterial peptide in preparation of antibacterial drugs for treating carbapenem-resistant pseudomonas aeruginosa, klebsiella pneumoniae (ATCC700603), escherichia coli (ATCC25922), staphylococcus aureus and methicillin-resistant staphylococcus aureus, the antibacterial peptide is characterized in that the sequence is w-r-r-w-k-r-w-w-r-r, and the sequence is shown in the description. All amino acids are D-type amino acids; the antibacterial peptide can be used as an antibacterial substance in wash supplies, food preservative additives, medical consumable antibacterial agents and cosmetics, can be synthesized through an Fmoc solid-phase chemical method, and is low in synthesis difficulty and good in in-vivo antibacterial activity. Particularly, the antibacterial peptide has broad-spectrum killing activity against carbapenem pseudomonas aeruginosa, klebsiella pneumoniae (ATCC700603), escherichia coli (ATCC25922), staphylococcus aureus and methicillin-resistant staphylococcus aureus, the cell survival rate of the antibacterial peptide within the range of medium and low concentration (2 mu g / mL-32 mu g / mL) reaches half or more, the toxicity is small, the toxicity is almost avoided, the operability is high, and the antibacterial peptide can be widely applied to the field of medical application. The cost is low.

The invention discloses an antibacterial peptide as well as a preparation method and application thereof. The antibacterial peptide has an amino acid sequence as shown in any one of SEQ ID NO: 1-11. The antibacterial peptide prepared by the scheme provided by the invention has very strong bacteriostasis and sterilization capabilities on methicillin-resistant staphylococcus aureus and multidrug-resistant escherichia coli, has application potential of becoming an antibacterial agent, a preservative or a disinfectant, and is not easy to generate drug resistance.

A method for functional antimicrobial peptide design is provided. The method includes running pretrained protein large language models as a generator and enhancing a sample candidate. The enhancing a sample candidate includes performing an automatic pipeline based on machine learning methods and a plurality of bioinformatics methods and is configured to perform protein inverse folding and computational protein sequence designing. The computational protein sequence designing includes running a pretrained deep learning-based protein structure model, an autoregressive pretrained protein sequence model, and a deep learning-based alignment model. The pretrained deep learning-based protein structure model is configured to learn three-dimensional structures of the proteins and output latent structure embeddings in a high dimensional space. The autoregressive pretrained protein sequence model includes a protein language model to automatically generate protein sequences and is trained to predict next amino acid in a protein sequence based on a preceding sequence(s) of amino acids.

The invention discloses an antibacterial peptide generation method, system, equipment and medium, and relates to the technical field of antibacterial peptide generation, the method comprises the following steps: obtaining protein sequence data; inputting the protein sequence data into an antibacterial peptide generation model for training, and performing autoregression sampling on the protein sequence data through an LSTM module to generate an amino acid sequence; inputting the amino acid sequence into a Transform module, performing word segmentation according to characters, converting the amino acid sequence after word segmentation into an id sequence, and mapping the id sequence into an embedded vector; encoding the embedded vector through an encoder, and inputting global features extracted by encoding into a decoder to generate a new amino acid sequence; identifying and screening the antibacterial characteristics of the new amino acid sequence to obtain an antibacterial peptide sequence; inputting to-be-generated protein sequence data into the trained antibacterial peptide generation model to generate an antibacterial peptide sequence; the method improves the novelty and antibacterial property of the new polypeptide sequence.

The invention belongs to the technical field of antibacterial peptides, and particularly relates to an LL-37 derived antibacterial peptide and application thereof. According to the invention, 17-29aa of the LL-37 antibacterial peptide is used as a core fragment and is connected with an amino acid sequence shown as SEQ ID NO: 1 or SEQ ID NO: 2 through an amido bond, the antibacterial activity of the obtained antibacterial peptide is obviously higher than that of the LL-37 antibacterial peptide, and the antibacterial peptide shows an obvious bactericidal effect on clinical drug-resistant bacteria such as acinetobacter baumannii, pseudomonas aeruginosa, escherichia coli, staphylococcus aureus, klebsiella pneumoniae and the like; meanwhile, the cytotoxicity and hemolytic activity are weak, drug resistance is not prone to being generated, bacteria can be rapidly killed in vivo through multiple mechanisms, no obvious cytotoxicity exists, the bacterium load in tissue is remarkably reduced, and the lifetime of a bacterium-infected mouse is prolonged.

The invention discloses an antibacterial peptide PPI45 / PPI47 as well as a preparation method and application of the antibacterial peptide PPI45 / PPI47. According to the invention, fungal defensin Plectasin is used as a template, and the self-assembled antibacterial peptide PPI45 / PPI47 is designed. The expression of the self-assembled antibacterial peptide PPI45 / PPI47 in pichia pastoris is realized by optimizing the gene sequence of the antibacterial peptide and constructing a specific expression vector, a perfect purification system is established, large-scale production can be realized, and the self-assembled antibacterial peptide PPI45 / PPI47 can be applied to the fields of antibacterial drug development, hydrogel wound treatment and the like, and has wide application value and market prospect.

The invention belongs to the field of antibacterial peptides, and particularly relates to a marine antibacterial peptide based on machine learning mining and application thereof. The invention discloses a method for mining marine antibacterial peptides based on machine learning, and 10 marine antibacterial peptides are screened, and the amino acid sequence of the marine antibacterial peptides is shown as any one of SEQ ID NO: 1-10. Wherein the Peptide 5 and the Peptide 8 have a broad-spectrum antibacterial characteristic, and the drug-resistant bacteria MIC (Minimum Inhibitory Concentration) of the Peptide 5 and the Peptide 8 is as low as 2-8 mu g / mL and is superior to that of The Peptide 2 and the Peptide 7 belong to strain specific antibacterial peptides, and are highly specific to bacillus subtilis. The antibacterial peptide has a wide application prospect in the field of preparation of antibacterial dressings and antibacterial drugs.

The invention discloses an antibacterial peptide quantitative activity prediction method based on multi-modal features and deep learning, and the method comprises the steps: S1, carrying out the preprocessing of an antibacterial peptide data set, dividing the data set into a training set and a test set, and generating a preprocessed data set; s2, based on the preprocessed data set, converting an antibacterial peptide sequence into a feature vector by utilizing four coding modes of protein language model embedding, BLOSUM62 coding, AAIndex coding and PAAC coding, and generating multi-modal feature representation; s3, on the basis of multi-modal feature representation, feature vectors of BLOSUM62 codes, AAIndex codes and PAAC codes are processed through a deep fusion feature extraction module, protein language model embedded features are processed through a protein language feature extraction module, and fusion features are generated; and S4, based on the fusion features, combining outputs of a deep fusion feature extraction module and a protein language feature extraction module, constructing a classification model, and performing activity classification on the new antibacterial peptide sequence to obtain a classification result.

The invention discloses a lactobacillus plantarum MW 2406C, which is preserved in China General Microbiological Culture Collection Center (CGMCC) on January 9, 2025, and the preservation number of the lactobacillus plantarum MW 2406C is CGMCC No. 33339. The inventor finds that the bacterial strain has better oxidation resistance, pathogenic bacterium inhibition and oxygen resistance, and can be used for effectively fermenting feed, pre-decomposing nutritional ingredients in the feed and improving the utilization efficiency of the feed; in addition, the strain can improve liver and intestine health and improve immunity by enhancing hepatopancreas antioxidant enzyme activity and intestinal digestive enzyme activity, improving intestinal barrier health, up-regulating antibacterial peptide level and reducing inflammatory factors. When the lactobacillus plantarum is used for preparing the fermented feed for the river crabs, the utilization efficiency of the compound feed by the river crabs is improved, the intestinal health of the river crabs is improved, and the disease resistance is improved.

The invention relates to a method for screening a high-yield exoprotein or polypeptide strain based on an antibacterial peptide. The method comprises the following steps: obtaining an eukaryotic expression strain of an exoprotein or polypeptide expression module integrated with an antibacterial peptide label; co-culturing the eukaryotic expression strain and antibacterial peptide sensitive bacteria on a solid plate, and observing the size of an inhibition zone of the exoprotein or polypeptide marked by the secreted antibacterial peptide in the growth process of the eukaryotic expression strain for inhibiting the growth of the antibacterial peptide sensitive bacteria; and screening according to the size of the inhibition zone to obtain the strain with high yield of the exosome protein or polypeptide. According to the method, the eukaryotic expression strain of high-performance protein or polypeptide exosome is visually displayed through the size of the inhibition zone, and the method has universality, can be suitable for detection of any protein, and is low in cost and easy in raw material obtaining.

The present invention discloses a sea dragon-derived antimicrobial peptide, SsPle, for antimicrobial applications in the complex environments of tropical islands and reefs. The amino acid sequence of this antimicrobial peptide is shown in SEQ ID NO. 3. This antimicrobial peptide, SsPle, exhibits good water solubility, broad antimicrobial activity, and highly stable antimicrobial properties under high temperature, high salt, and ultraviolet irradiation conditions. It can inhibit the release of free bacterial endotoxins and has significant application prospects as an eco-friendly antimicrobial agent in the unique environments of South China Sea islands and reefs.

The invention provides a modified antibacterial peptide, and belongs to the technical field of antibacterial peptides. The invention provides a modified antibacterial peptide. The modified antibacterial peptide comprises at least one of a first antibacterial peptide, a second antibacterial peptide, a third antibacterial peptide, a fourth antibacterial peptide, a fifth antibacterial peptide and a sixth antibacterial peptide, the amino acid sequences of the first antibacterial peptide, the second antibacterial peptide, the third antibacterial peptide, the fourth antibacterial peptide, the fifth antibacterial peptide and the sixth antibacterial peptide are shown as SEQ ID NO.1-SEQ ID NO.6 in sequence. On the basis of prevotelin-2, the modified antibacterial peptide is obtained by reducing negative charge amino acid, increasing positive charge amino acid, introducing hydrophobic amino acid, adjusting or deleting an amino acid sequence and optimizing a polypeptide structure. In-vitro minimum inhibitory concentration determination results show that compared with an initial peptide, the modified antibacterial peptide has significantly enhanced antibacterial activity on bacteria and fungi, and also has an obvious bactericidal effect on clinical drug-resistant bacteria.

The invention relates to the technical field of antibacterial peptides, in particular to an antibacterial peptide RF-18 and application thereof in preparation of antibacterial products. The amino acid sequence of the antibacterial peptide RF-18 provided by the invention is as shown in SEQ ID NO. 1. The antibacterial peptide RF-18 provided by the invention is an antibacterial peptide capable of being artificially synthesized and only contains 18 amino acids, and all the amino acids are L-type amino acids, so that the production cost is greatly reduced; besides, the antibacterial peptide RF-18 provided by the invention is a novel antibacterial peptide with an imperfect amphiphilic structure, not only can exert efficient and broad-spectrum antibacterial activity, but also has extremely high safety, has no cytotoxicity or hemolysis effect in a concentration range of 800 mu g / mL, and can be used for preparing antibacterial infection drugs.

The invention belongs to the technical field of polypeptide drugs in biochemistry, and discloses three antibacterial peptide analogues as well as a preparation method and application thereof, the sequence of an antibacterial peptide P-1 is CH3CO-GGGENIKKILSKIKLLK-NH2, the sequence of an antibacterial peptide P-2 is CH3CH2CH2CO-GGGENIKKILSKIKLLK-NH2, the sequence of an antibacterial peptide P-3 is CH3 (CH2) 6CO-GGGENIKKILSKIKLLK-NH2, the carboxyl ends of polypeptides are subjected to amidation, and the polypeptides are all positively charged when the pH is equal to 7. The artificially synthesized antibacterial peptide disclosed by the invention shows a remarkable sterilization effect on multidrug resistant staphylococcus epidermidis. P-1, P-2 and P-3 have small molecular weight, are convenient to synthesize, have broad-spectrum bactericidal activity, are self-assembled into nanoparticles, have low cytotoxicity, resist trypsin degradation and the like, and have wide application prospects.

The invention discloses a method for constructing an antibacterial peptide Apidaecin IB high-expression genetically engineered bacterium, which comprises the following steps of: 1, designing three pairs of primers according to a DNA sequence of an amplification template coding region, carrying out PCR (Polymerase Chain Reaction) amplification, and constructing expression plasmids in escherichia coli; step 2, carrying out multiplication culture on engineering bacteria saccharomyces cerevisiae CENPK2, preparing saccharomyces cerevisiae competent cells, and subpackaging and refrigerating for later use; step 3, carrying out enzyme digestion on the constructed expression plasmid, and carrying out mixed transformation on the expression plasmid and a competent cell of saccharomyces cerevisiae CENPK2, so as to obtain the high-expression genetic engineering bacterium CENPK2-Apidaecin IB-Ty1Cons2 of the antibacterial peptide Apidaecin IB, wherein the high-expression genetic engineering bacterium CENPK2-Apidaecin IB-Ty1Cons2 is obtained; according to the invention, the Ty1Cons2 transposon is integrated into the saccharomyces cerevisiae CENPK2, so that the construction of the high-expression gene engineering bacterium of the antibacterial peptide Apidaecin IB is completed, and multiple copies are realized.

The invention belongs to the technical field of plant disease control, and particularly relates to preparation and application of diaphorina citri sourced antibacterial peptide DcAMP2. The amino acid sequence of the antibacterial peptide DcAMP2 is SEQ ID NO. 1, and the nucleotide sequence of the gene for coding the antibacterial peptide DcAMP2 is SEQ ID NO. 2. The prokaryotic expression plasmid is adopted to construct the recombinant plasmid containing the gene encoding the antibacterial peptide DcAMP2, prokaryotic expression of the antibacterial peptide DcAMP2 is achieved, and the method is simple and easy to implement. After being purified, the antibacterial peptide DcAMP2 obtained through prokaryotic expression has an obvious antibacterial effect on a liberobacter asiaticum related bacterium sinorhizobium fredii, and the titer of the liberobacter asiaticum in a sweet orange tree with the liberobacter asiaticum can be obviously reduced.

Peptides that bind with high affinity to oral cavity surfaces, such as tooth enamel, have been discovered. The peptides exhibit antibacterial and mineralizing abilities, and are useful in many aspects of oral care. The peptides include the amino acid sequence AKRHHGYKRKFH-SpSp. The peptides can be included in oral care compositions such as toothpastes and mouthwashes. The oral care compositions can be used in methods to treat or prevent diseases or conditions induced by acidophilic oral bacteria. Exemplary methods include reducing or preventing tooth decay or demineralization, biofilm or dental plaque formation, and / or bacterial adhesion to a tooth surface; and promoting mineralization of teeth surfaces.

The invention discloses an antibacterial small peptide CsCAPE9 and application of the antibacterial small peptide CsCAPE9 in prevention and control of citrus huanglongbing. The amino acid sequence of the antibacterial small peptide CsCAPE9 is as shown in SEQ ID NO.1; the antibacterial small peptide CsCAPE9 provided by the invention is a small peptide synthesized in a plant body, and the antibacterial small peptide CsCAPE9 can activate biosynthesis of salicylic acid and induce systematic defense reaction of citrus. The antibacterial small peptide CsCAPE9 has a good inhibition effect on pathogenic bacteria of citrus huanglongbing in greenhouses and fields, and has a wide application prospect in comprehensive prevention and control of the huanglongbing.

The invention discloses combined lactobacillus salivarius CCFM1332 with a multi-target regulation effect and application of the combined lactobacillus salivarius CCFM1332 in periodontitis, and belongs to the technical field of microorganisms. The invention discloses a strain of combined lactobacillus salivarius CCFM1332, and the combined lactobacillus salivarius not only has a vaginal immune regulation effect, but also has an effect of relieving periodontitis, which is specifically embodied in that: the combined lactobacillus salivarius can promote vaginal epithelial cells VK2 / E6E7 to secrete antibacterial peptides; the periodontal probing and diagnosing depth of the periodontitis rats can be reduced; the number of pathogenic bacteria in the oral cavity of the periodontitis rat is reduced; the levels of inflammatory factors IL-1beta, IL-6 and IL-17A in serum are reduced; alveolar bone loss of rats suffering from periodontitis is reduced, and the alveolar bone absorption condition of the rats is effectively relieved.