48 results about "Cryptococcus gattii" patented technology

The invention discloses a YOLOv8 cryptococcus polymorphic detection and counting method and system based on hypergraph calculation, the method uses a YOLOv8 model based on hypergraph calculation to carry out cryptococcus polymorphic detection and counting, and the method comprises the following steps: obtaining a cryptococcus image to be detected and counted; the CSPDarknet backbone network is used for carrying out feature extraction on the cryptococcus polymorphic image; the neck network based on hypergraph calculation performs adaptive detection on cryptococcus with different morphological characteristics, and introduces an attention mechanism to enhance the perception ability of the model to a target; the head network generates a density estimation graph; the adaptive density fusion network aggregates coarse-grained cryptococcus density information; optimizing density estimation based on a loss function of distributed supervision; and outputting detection and counting results. According to the method, adaptive detection of the cryptococcus with different morphological characteristics is realized through hypergraph calculation, automatic counting of the cryptococcus is realized through counting of the density map estimation graph, and the accuracy of feature counting of significant morphological differences and dense small targets presented by the cryptococcus image is high.

The invention discloses a macrophage-polymer lipid nanoparticle composite drug delivery system, a preparation method thereof and application of the macrophage-polymer lipid nanoparticle composite drug delivery system in cryptococcus infection resistance. According to the drug delivery system, alpha-linolenic acid (ALA), high molecular weight chitosan oligosaccharide (HCOS) and amphotericin B (AmB) are used as raw materials to construct nanoparticles AmB-PLHNs, the nanoparticles are loaded in macrophages through the phagocytosis of the macrophages, and the AmB-PLHNs (at) M1 is constructed. AmB is a common medicine for clinically treating Cn infection, but has the problems of toxic and side effects on kidney and incapability of being transferred into the center. The AmB-PLHNs (at) M1 carries AmB-PLHNs to be transferred into the brain according to the blood-brain barrier penetrating characteristic of M1 type macrophages, and the brain entering efficiency of the medicine is improved. By combining the phagocytosis of macrophages on cryptococcus, the inflammation immune regulation function of the macrophages and the bacteriostatic action of the drug-loaded nanoparticles, the drug-loaded nano-particles are used for treating Cn central infection, and the toxic and side effects of AmB are reduced.

The invention discloses a cryptococcus capsular thickness detection method and system based on image processing, and relates to the technical field of image processing, and the method comprises the steps: obtaining preset parameter information corresponding to a to-be-detected cryptococcus image based on a cryptococcus parameter database; detecting an edge image of the to-be-detected cryptococcus image, and processing the edge image to obtain an edge curve; circularly extracting pixel points of the edge curve, and dividing to form at least one circumcircle; performing image segmentation on the circumcircle to form at least one to-be-detected cryptococcus subimage, and marking initial quantity information; acquiring a thickness curve to obtain initial thickness information; performing detection error calculation on the initial quantity information and preset quantity information, updating and outputting target quantity information, performing detection error calculation on the initial thickness information and preset thickness information, and updating and outputting target thickness information. The accuracy is low; and the error is large.

Described are immunogenic compositions comprising a non-naturally occurring pan-fungal Kex peptide, and methods of using such compositions for the treatment or prevention of infection and / or diseases associated with fungal pathogens (e.g., Pneumocystis, Aspergillus, Candida, or Cryptococcus) in the subject. Also provided are compositions and kits for detecting or quantifying the presence of antibodies directed against a non-naturally occurring pan-fungal Kex peptide in a subject.

The invention discloses a cryptococcus capsular polysaccharide detection kit. The cryptococcus capsular polysaccharide detection kit comprises a biotin-labeled cryptococcus monoclonal antibody and an acridinium ester-labeled cryptococcus monoclonal antibody, wherein the biotin-labeled cryptococcus monoclonal antibody and the acridinium ester-labeled cryptococcus monoclonal antibody are coupled with streptavidin magnetic beads. According to the cryptococcus capsular polysaccharide detection kit disclosed by the invention, the biotin-labeled cryptococcus monoclonal antibody coupled with the streptavidin magnetic beads and the acridinium ester-labeled cryptococcus monoclonal antibody are matched, so that the cryptococcus capsular polysaccharide detection kit has relatively strong recognition capability on various serotypes of cryptococcus, and the antibodies do not interfere with one another; according to the cryptococcus capsular polysaccharide detection kit, the detection sensitivity and the detection accuracy can be greatly improved, the problem that a detection result is greatly influenced by subjective consciousness and is inaccurate due to the fact that an existing detection method only depends on visual inspection is solved, and the cryptococcus capsular polysaccharide detection kit is convenient to operate, facilitates automatic operation of an instrument and reduces manual errors.

The invention relates to diphenyl ether compounds with anti-cryptococcus activity. The invention discloses an application of a diphenyl ether compound in preparation of a medicine for inhibiting the activity of cryptococcus. The compound has good inhibitory activity on multiple strains of cryptococcus sp. And is suitable for research on an anti-cryptococcus active lead compound or preparation of an anti-cryptococcus medicine.

The application provides an application of a compound HEX and / or a compound POM-HEX in medicine for preventing and / or treating fungal infection, and belongs to the technical field of medicine. In vitro experiments show that POM-HEX alone has inhibiting effects on candida and cryptococcus, and when combined with fluconazole, the antifungal activity can be significantly improved, and the drug-resistant strains can restore the sensitivity to fluconazole. The organ bacterial load experiment in mice in vivo proves that POM-HEX can stably exert the drug efficacy in the organism. In addition, the IC 50 value of the metabolic product HEX of POM-HEX for inhibiting the Eno1 enzyme activity of Candida albicans is 1 / 30 of the IC 50 of HEX for inhibiting the Eno1 enzyme activity of human. The application discloses that the HEX and / or the compound have strong antifungal activity and high selectivity for the target point Eno1, provides a new idea for antifungal treatment, the drug combination can reduce the drug dosage, reduce the toxic and side effects, and solves the problem of fungal drug resistance.

The invention discloses a cryptococcal capsule thickness detection method and system based on image processing, and relates to the technical field of image processing. The method comprises: obtaining preset parameter information corresponding to a cryptococcal image to be detected based on a cryptococcal parameter database; detecting an edge image of the cryptococcal image to be detected, processing the edge image, and obtaining an edge curve; cyclically extracting pixel points of the edge curve, dividing and forming at least one circumscribed circle; performing image segmentation on the circumscribed circle to form at least one cryptococcal sub-image to be detected, and marking initial quantity information; obtaining a thickness curve, and obtaining initial thickness information; performing detection error calculation on the initial quantity information and the preset quantity information, and updating the output target quantity information; performing detection error calculation on the initial thickness information and the preset thickness information, and updating the output target thickness information. The invention solves the problem of low accuracy and large error in the prior art of using a microscope to observe and judge the capsule thickness of cryptococci.

The application discloses application of gynostemma pentaphyllum saponin H combined with azole drugs in preparation of antifungal drugs and the antifungal drugs, and relates to the technical field of antifungal drugs. It is found through systematic in-vitro drug sensitivity test that natural product gynostemma pentaphyllum saponin H combined with specific azole antifungal drugs (especially posaconazole POS) can produce significant synergistic antifungal effect, especially for clinical thorny aspergillus, candida, new cryptococcus and dark fungi. The combination strategy can significantly reduce the minimum inhibitory concentration of azole drugs, reverse drug resistance, and is effective for multi-drug resistant strains (such as candida auris). The application provides an efficient and low-toxicity new combination drug scheme for overcoming the increasingly serious fungal drug resistance problem.

The invention belongs to the technical field of medicines, and relates to an azole compound as well as a preparation method and application thereof. The azole compound or the pharmaceutically acceptable salt thereof has a structure as shown in general formulas I and II: # imgabs0. The azole compound provided by the invention has an excellent bactericidal effect on various cryptococcus and filamentous fungi.

The invention relates to the technical field of pharmacy, in particular to an aryl dihydronaphthalene type lignan analogue with antibacterial activity as well as a preparation method and application thereof, and the aryl dihydronaphthalene type lignan analogue is a compound with a structure as shown in a formula (I) or a pharmaceutically acceptable prodrug thereof. The specific preparation method comprises the following steps: (1) carrying out ring opening on sesamin ether bonds to prepare acetate 2; (2) performing deacetylation protection on the compound 2 to prepare alcohol 3; and (3) carrying out Des-Martin oxidation on the alcohol 3 to prepare aldehyde 4 and aldehyde 5. The aryl dihydronaphthalene lignan analogue synthesized by the invention has certain activity on Candida albicans (C.albicans), Cryptococcus neoformans (C.neoformans) and T.mentagrophytes (T.mentagrophytes), the compound 5 has good activity on the three types of bacteria, the IC50 values of the three types of bacteria are respectively 28.96 mu M, 17.13 mu M and 41.35 mu M, and the aryl dihydronaphthalene lignan analogue has certain application prospects in the development of corresponding medicines.

This invention belongs to the field of fungal detection technology, specifically relating to a micro-platform for rapid electrolysis and highly sensitive electrochemical nucleic acid detection of Cryptococcus neoformans and its application. The micro-platform includes an integrated microfluidic chip, an external power supply, a sample introduction system, and / or an imaging system. The integrated microfluidic chip includes an electrolysis region, an electrochemical detection region, and an electrode array region. The electrolysis region includes multiple vertically arranged counter electrodes arranged in pairs, and multiple horizontally arranged hollow channels in a serpentine pattern, bonded to the electrode pairs above them. The connection point between every two electroporated channels is the electroporation lysis point. The electrochemical detection region consists of a working electrode, a reference electrode, and a counter electrode. The working electrode is modified with rGO / AuNPs nanomaterials and molecular probes.

Provided are a combination of an inositol phosphorylceramide synthase inhibitor and amphotericin B and use thereof. The use includes preparing a pharmaceutical composition, which includes an inositol phosphorylceramide synthetase inhibitor and amphotericin B or a salt thereof. Inositol phosphorylceramide is an important and conserved component of fungal plasma membranes. In the pharmaceutical composition according to an embodiment of the present disclosure, due to the presence of the inositol phosphorylceramide synthase inhibitor, the interaction between the inositol phosphorylceramide synthase inhibitor and amphotericin B not only enhances the inhibitory ability of the inositol phosphorylceramide synthase inhibitor on the synthesis of inositol phosphorylceramide in Cryptococcus, but also effectively reduces the dosage of amphotericin B and prolongs the half-life of amphotericin B, facilitating to reduce the adverse reactions of amphotericin B. The pharmaceutical composition exhibits superior fungicidal effect and safety compared to the currently used clinical combination of 5-fluorocytosine and amphotericin B.

The application discloses a biosynthesis gene cluster of a polyene macrolide natural product mandimycin, and a natural product and application of the biosynthesis gene cluster, wherein the nucleotide sequence of the biosynthesis gene cluster is shown as SEQ ID NO. 1, and the compound structural formula of the natural product mandimycin and mandimycin B is shown as formula I and formula II. The natural product mandimycin can target fungal cell membrane phospholipid molecules, especially phosphatidylinositol, cause important ion efflux in fungal cells, and lead to fungal cell death. The natural product mandimycin and mandimycin B have strong in-vivo and in-vitro antibacterial activity and a broad antibacterial spectrum on various WHO-published multiple drug-resistant fungal key pathogens, including candida, aspergillus, cryptococcus, mucor and fusarium.

The invention discloses a preparation method and application of a 1-(2-((3-methoxy-2-(6-methoxyquinoline-3-yl)-3-oxoethyl) amino)-2-oxoethyl) piperidine-4-formamide compound. The structure of the compound is shown as a general formula 1, wherein R in the formula is various substituted aromatic rings, thiazole, naphthalene rings, aliphatic chains and the like. An enzyme inhibition activity experiment result shows that part of the compounds have a relatively strong inhibition effect on chitin synthetase and also have a relatively strong inhibition effect on fungi such as candida albicans, aspergillus flavus, cryptococcus neoformans and aspergillus fumigatus. A drug resistance activity test result shows that part of the compounds have certain inhibitory activity on variant thalli such as fluconazole-resistant candida albicans, fluconazole-resistant cryptococcus neoformans and micafungin-resistant candida albicans, and have the potential of coping with the drug resistance problem. The compounds are simple and cheap in preparation raw materials and simple and convenient in synthesis method, and can be used as lead compounds for designing antifungal drugs.

The invention relates to a five-membered heteroaryl compound and application thereof, the compound is a compound with a structural formula shown in the specification or pharmaceutically acceptable salts and prodrugs thereof, in the formula, R1 is selected from CH3 and H; r2 is selected from NH2 and OH; r3 is selected from CH3 and H; r4 is selected from OH, F and H; r5 is selected from NO2 and H; r6 is selected from CN, NO2 and H; and L1 is selected from-CH2O <-> and-CH2-CH2 <->, and-CH is equal to CH <->. A series of five-membered heteroaryl compounds are researched and developed on the basis of an APX001A structure, and the five-membered heteroaryl compounds have a good Gwtl protein binding effect and can inhibit Gwtl protein activity, so that GPI-AP synthesis is prevented, mannose glycoprotein on the fungal surface cannot be cross-linked to a cell wall, the host surface adhesion capacity and cell wall integrity of the mannose glycoprotein are destroyed, the antifungal effect is achieved, and the application prospect is broad. The compound has good inhibitory activity on candida, cryptococcus and aspergillus.

The application provides a set of primers and probes for detecting invasive fungi, reagents and application thereof, a kit and a detection method, and relates to the technical field of biology.The nucleic acid sequence of the primer is shown as SEQ ID NO.1-2, 4-5, 7-11, 14-15, 17-18 and 20-21; and the nucleic acid sequence of the probe is shown as SEQ ID NO.3, 6, 12-13, 16, 19 and 22.The primers and probes have high specificity and sensitivity, and can be used for the detection and identification of Aspergillus, Mucorales, Cryptococcus neoformans, Pneumocystis jirovecii and Lichtheimia. The kit for detecting invasive fungi has high specificity and sensitivity, and wide fungal coverage, and can realize the detection of multiple invasive fungi simultaneously.

The invention discloses a composition, a kit and a detection method for detecting pulmonary infection pathogens. The composition comprises at least one of a component A, a component B, a component C and a component D, the component A comprises a primer pair SEQ ID NO: 1-2 and a probe SEQ ID NO: 3; detecting bordetella pertussis by the component A; the component B comprises a primer pair SEQ ID NO: 4-5 and a probe SEQ ID NO: 6; the component B is used for detecting Nocardia; the component C comprises a primer pair SEQ ID NO: 7-8 and a probe SEQ ID NO: 9; detecting cryptococcus neoformans by the component C; the component D comprises a primer pair SEQ ID NO: 10 to 11 and a probe SEQ ID NO: 12; the component D is used for detecting acinetobacter baumannii. The composition for detecting the pulmonary infection pathogens provided by the invention can detect and distinguish at least one of bordetella pertussis, nocardia, cryptococcus neoformans and acinetobacter baumannii, has higher sensitivity, specificity and precision, can accurately and quickly detect bordetella pertussis, nocardia, cryptococcus neoformans and acinetobacter baumannii, and can be used for detecting the pulmonary infection pathogens. The detection efficiency is improved, the detection period is shortened, and detection is convenient.

The application relates to a kind of five-membered heteroaryl antifungal compounds and its application, the structural formula of the compound is as shown below:;Wherein, Ar is selected from the group consisting of,, and,;R1 It is selected from F and H;R2 It is selected from F and H;R3 It is selected from NO2, CN and H;R4 It is selected from CN and H;R5 It is selected from CN, F and H;L1 It is selected from-CH2O-, -OCH2- and-O-;T1 It is selected from N and CH.The application develops a series of five-membered heteroaryl compounds on the basis of APX001A structure, has good Gwt1 protein binding, can inhibit Gwt1 protein activity, thereby prevent GPI-AP synthesis, lead to the surface of fungi mannose protein cannot be crosslinked on cell wall, further destroy its adhesion host surface ability and cell wall integrity, play antifungal effect, have good inhibitory activity to candida, cryptococcus and aspergillus.

The present application belongs to the field of biotechnology and medicine, and relates to a centromere binding protein Cbf1, a coding gene thereof and application. Specifically, the present application provides a Cryptococcus virulence related protein, which is a centromere binding protein Cbf1. Meanwhile, the present application also provides application of the centromere binding protein Cbf1 in preparation of a medicine, CBF1 Gene knockout leads to reduction of tolerance of the strain to 37 DEG C, oxidation and cell wall pressure, and reduction of melanin production, so that the protein can be used as a drug target and applied to research and development of a new drug for treating diseases caused by Cryptococcus.

Pathogens developing resistance to available drugs are of main concern in various diseases, including cryptococcosis and tuberculosis. Hence there is a need for therapeutics with novel mechanisms of action. Described herein are compositions and methods for treating infections (e.g., fungal infections) caused by microbes (e.g., fungi) comprising inteins. An intein is a moving protein element inside a host protein. Splicing off intein from the host protein is required to maturate and activate the host protein. Calcimycin (CMN) is used as an intein splicing inhibitor to block intein splicing of the Prp8 protein of fungal pathogen C. neoformans and C. gattii the causative agents of cryptococcosis, to treat patients.

The invention specifically discloses a risk biomarker for cryptococcus meningitis and application thereof, and relates to the technical field of biological medicines. The invention provides a brand new cryptococcus brain infection antivirulence factor mitochondrial citric acid transporter: by closing the mitochondrial citric acid transporter, glucose metabolism hijacking in the brain is realized, and the colonization advantage is obtained.

The present invention provides a fungal drug carrier comprising an avirulent fungal pathogen cell, for example a Cryptococcus neoformans cell, linked to one or more surface-bound drug-loaded nanoparticles, and methods of making the fungal drug carrier. The invention provides methods of using the fungal drug carrier to deliver a drug to the central nervous system of a patient, wherein the fungal drug carrier is phagocytosed by an immune cell of a patient, transported across the blood-brain barrier, and vomocytosed to allow drug release from the surface-bound nanoparticle into the central nervous system of the patient. The methods involve treating a central nervous system in a patient comprising administering to the patient a pharmaceutical composition comprising a fungal drug carrier.

This invention provides a novel target PDE4B for the prevention and treatment of Cryptococcus neoformans brain infection. Specifically, it relates to the application of drugs targeting phosphodiesterase PDE4B in the preparation of drugs for the prevention and / or treatment of Cryptococcus neoformans meningoencephalitis. The drug targeting PDE4B is the PDE4B agonist MR-L2 (CAS: 2374703-19-0). The PDE4B agonist MR-L2 described in this invention can significantly reduce Cryptococcus neoformans brain infection, providing an effective prevention and treatment method for Cryptococcus neoformans meningoencephalitis.

The invention belongs to the technical field of biological medicine, and provides an anti-cryptococcus antigen-antibody pair and application thereof in a chemiluminescence method kit. The anti-cryptococcus antigen and antibody pair comprises an anti-cryptococcus capsular polysaccharide monoclonal antibody GMX-2H12 and an anti-cryptococcus capsular polysaccharide monoclonal antibody GMX-4B09; the anti-cryptococcus capsular polysaccharide monoclonal antibody GMX-2H12 has a light chain variable region of which the amino acid sequence is as shown in SEQ ID NO.1 and a heavy chain variable region of which the amino acid sequence is as shown in SEQ ID NO.2; the anti-cryptococcus capsular polysaccharide monoclonal antibody GMX-4B09 has a light chain variable region of which the amino acid sequence is as shown in SEQ ID NO.3 and a heavy chain variable region of which the amino acid sequence is as shown in SEQ ID NO.4. According to the present invention, the anti-cryptococcus capsular polysaccharide monoclonal antibody GMX-2H12 is combined with the conformation-dependent epitope of the beta-1, 2-xylose side chain, the anti-cryptococcus capsular polysaccharide monoclonal antibody GMX-4B09 recognizes the O-acetylation modified linear epitope, and the detection blind area caused by antigen oligomerization is effectively avoided through the double-epitope sandwich method design;

The invention relates to the technical field of biological detection, in particular to a primer probe composition for a fungal infection detection system, which comprises an upstream primer, a downstream primer and a fluorescent probe designed aiming at candida auricula, and an upstream primer, a downstream primer and a fluorescent probe designed aiming at cryptococcus gattii (cryptococcus neoformans). The upstream primer, the downstream primer and the fluorescent probe are designed aiming at histoplasma capsulatum, the upstream primer, the downstream primer and the fluorescent probe are designed aiming at trichosporon crassiforme, and the upstream primer, the downstream primer and the fluorescent probe are designed aiming at paracoccus brazilii; the invention also relates to a method for simultaneously detecting and quantifying five clinical important yeast-like pathogenic fungi by combining a fluorescent quantitative polymerase chain reaction (qPCR) and a digital polymerase chain reaction (dPCR). Therefore, the problem that multiple pathogenic fungi cannot be detected at the same time during single pathogen detection is solved; or although multiple detection is carried out, accurate quantification is difficult, and the like.

The application discloses a new MNP marker site of Cryptococcus neoformans, a primer composition, a kit and application thereof, wherein the MNP marker site refers to a genomic region screened on a genome of the Cryptococcus neoformans, which is distinguished from other species and has multiple nucleotide polymorphisms in the species, and at least one of the marker sites of MNP-1 to MNP-3; the primer is shown as SEQ ID NO. 1 to SEQ ID NO. 6. The primer pair combination is a multiplex PCR amplification primer designed to amplify the MNP marker in one reaction; the kit integrates multiplex PCR amplification and next-generation sequencing technology, performs sequence analysis on multiple MNP markers of the Cryptococcus neoformans in the sample in one reaction, and has the technical advantages of high throughput, multiple targets, high sensitivity, high precision, culture-free in the application of epidemic prevention monitoring, scientific research and variation monitoring of the Cryptococcus neoformans.

The invention discloses a novel medical application of sodium new houttuyfonate in prevention and treatment of pathogenic bacteria, including application of sodium new houttuyfonate in preparation of drugs for prevention and treatment of pathogenic fungus infection or drugs for inhibition of pathogenic fungi. The pathogenic fungi are selected from one or more of cryptococcus neoformans, cryptococcus gattii, trichophyton rubrum, trichophyton purple, microsporum canis, candida niticola complex bacteria, candida albicans, trichophyton mentagrophytes and trichophyton broken. Researches show that sodium new houttuyfonate has important significance in preventing and treating infection of different pathogenic bacteria, especially has a remarkable curative effect on cryptococcus neoformans lung infectious diseases and skin traumatic infectious diseases, and compared with traditional antibacterial drugs, the sodium new houttuyfonate is not prone to causing drug resistance of pathogenic bacteria and has a good application prospect. The compound is expected to be developed into a candidate drug for clinically treating different pathogenic bacteria, is efficient, non-toxic and broad-spectrum, is expected to solve the problem of drug resistance of the pathogenic bacteria, and has a good application prospect.

The invention discloses an application of ultrasonic microvesicle combined amphotericin B in preparation of a medicine for treating cryptococcus meningitis. The invention provides a treatment strategy combining ultrasound microvesicles with amphotericin B, and aims to improve the prognosis of cryptococcus meningitis. Experiments show that after ultrasound is combined with microbubble intervention, the intracerebral concentration of amphotericin B of a CM mouse is increased to 1.7 times of the original concentration, the load capacity of cryptococcus is reduced by 97%, the survival rate in 60 days is increased to 100% from 50%, and the curative effect is superior to that of single-drug treatment. Effectiveness is verified in an animal model, the antifungal drug is adaptive to existing antifungal drugs (amphotericin B deoxycholate and liposome amphotericin B), new drugs do not need to be developed, and the research and development cost is reduced.